bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining photodynamic therapy and cascade chemotherapy for enhanced tumor cytotoxicity: the role of CTT2P@B nanoparticles
Authors: Wang Rongyi , Li Hongsen , Han Lu , Han Boao , Bao Yiting , Fan Hongwei , Sun Chaoyue , Qian Ruijie , Ma Liying , Zhang Jiajing 
Published: February 2024

The mitochondria act as the main producers of reactive oxygen species (ROS) within cells. Elevated levels of ROS can activate the mitochondrial apoptotic pathway, leading to cell apoptosis. In this study, we devised a molecular prodrug named CTT2P, demonstrating notable efficacy in facilitating mitochondrial apoptosis. To develop nanomedicine, we enveloped CTT2P within bovine serum albumin (BSA), resulting in the formulation known as CTT2P@B. The molecular prodrug CTT2P is achieved by covalently conjugating mitochondrial targeting triphenylphosphine (PPh3), photosensitizer TPPOH2, ROS-sensitive thioketal (TK), and chemotherapeutic drug camptothecin (CPT). The prodrug, which is chemically bonded, prevents the escape of drugs while they circulate throughout the body, guaranteeing the coordinated dispersion of both medications inside the organism. Additionally, the concurrent integration of targeted photodynamic therapy and cascade chemotherapy synergistically enhances the therapeutic efficacy of pharmaceutical agents. Experimental results indicated that the covalently attached prodrug significantly mitigated CPT cytotoxicity under dark conditions. In contrast, TPPOH2, CTT2, CTT2P, and CTT2P@B nanoparticles exhibited increasing tumor cell-killing effects and suppressed tumor growth when exposed to light at 660 nm with an intensity of 280 mW cm−2. Consequently, this laser-triggered, mitochondria-targeted, combined photodynamic therapy and chemotherapy nano drug delivery system, adept at efficiently promoting mitochondrial apoptosis, presents a promising and innovative approach to cancer treatment.
Pulmonary vein capture is a predictor for long-term success of stand-alone pulmonary vein isolation with cryoballoon ablation in patients with persistent atrial fibrillation
Authors: Babak Alexey , Kauffman Christine Bienvenue , Lynady Cynthia , McClellan Reginald , Venkatachalam Kalpathi , Kusumoto Fred 
Published: February 2024

BackgroundThe mechanisms of AF development and progression are still not completely understood. Despite the relative efficacy of ablation, the risk of AF recurrence is substantial, particularly in patients with persistent AF (perAF). At present we do not have any reliable intra-procedural electrophysiologic predictors of long-term success of AF ablation other than pulmonary vein isolation. We evaluated selected intraprocedural pulmonary vein characteristics that may be helpful in future guidance of persistent AF ablation.Methods390 consecutive procedures using cryoballoon for initial AF ablation were divided by clinical presentation (paroxysmal or persistent AF), and by pulmonary vein (PV) response to pacing after completion of ablation (discrete electrogram elicited with pacing—“PV capture” or not—“Control”). Patients were followed (median 20 months) for recurrent atrial arrhythmias as the primary end point of the study.ResultsPV capture was identified in 20.3% and 17.1% and patients with paroxysmal and persistent AF respectively (ns). In patients with persistent AF presence of PV capture was associated with significantly better outcomes compared to patients without PV capture (p &lt; 0.001). In the group “persistent AF and PV capture”, an initial strategy of PV isolation and reisolation of the PVs (without additional lesions) for patients with recurrent atrial arrhythmias resulted in 20/23 (87%) patients in sinus rhythm off antiarrhythmic medications at study completion. In patients with paroxysmal AF, PV capture was not associated with outcome benefits. Speciﬁc electrophysiologic characteristics of PV (PV capture cycle length: PVCCL) did not have an impact on AF recurrence, although 25% shortening of PVCCL was observed after 60 s periods of pacing at short cycle lengths. No background demographic patient characteristic differences were identiﬁed between patients with vs. without PV capture.ConclusionThe presence of PV capture was associated with better outcomes in patients with persistent AF. PV capture may identify those patients with persistent AF in whom cryoballoon PV isolation alone is sufficient as an initial ablation procedure and as the primary ablation strategy for recurrent AF.
Up-regulated expression of two-pore domain K+ channels, KCNK1 and KCNK2, is involved in the proliferation and migration of pulmonary arterial smooth muscle cells in pulmonary arterial hypertension
Authors: Shima Natsumi , Yamamura Aya , Fujiwara Moe , Amano Taiki , Matsumoto Kazuyuki , Sekine Taiga , Okano Haruka , Kondo Rubii , Suzuki Yoshiaki , Yamamura Hisao 
Published: February 2024

BackgroundPulmonary arterial hypertension (PAH) is a severe and rare disease in the cardiopulmonary system. Its pathogenesis involves vascular remodeling of the pulmonary artery, which results in progressive increases in pulmonary arterial pressure. Chronically increased pulmonary arterial pressure causes right ventricular hypertrophy and subsequent right heart failure. Pulmonary vascular remodeling is attributed to the excessive proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), which are induced by enhanced Ca2+ signaling following the up-/down-regulation of ion channel expression.ObjectivesIn the present study, the functional expression of two-pore domain potassium KCNK channels was investigated in PASMCs from idiopathic PAH (IPAH) patients and experimental pulmonary hypertensive (PH) animals.ResultsIn IPAH-PASMCs, the expression of KCNK1/TWIK1 and KCNK2/TREK1 channels was up-regulated, whereas that of KCNK3/TASK1 and KCNK6/TWIK2 channels was down-regulated. The similar up-regulated expression of KCNK1 and KCNK2 channels was observed in the pulmonary arterial smooth muscles of monocrotaline-induced PH rats, Sugen 5416/hypoxia-induced PH rats, and hypoxia-induced PH mice. The facilitated proliferation of IPAH-PASMCs was suppressed by the KCNK channel blockers, quinine and tetrapentylammonium. The migration of IPAH-PASMCs was also suppressed by these channel blockers. Furthermore, increases in the proliferation and migration were inhibited by the siRNA knockdown of KCNK1 or KCNK2 channels. The siRNA knockdown also caused membrane depolarization and subsequent decrease in cytosolic [Ca2+]. The phosphorylated level of c-Jun N-terminal kinase (JNK) was elevated in IPAH-PASMCs compared to normal-PASMCs. The increased phosphorylation was significantly reduced by the siRNA knockdown of KCNK1 or KCNK2 channels.ConclusionCollectively, these findings indicate that the up-regulated expression of KCNK1 and KCNK2 channels facilitates the proliferation and migration of PASMCs via enhanced Ca2+ signaling and JNK signaling pathway, which is associated with vascular remodeling in PAH.
Monitoring coronary blood flow by laser speckle contrast imaging after myocardial ischaemia reperfusion injury in adult and aged mice
Authors: El-Awaisi Juma , Kavanagh Dean P. J. , Kalia Neena 
Published: February 2024

IntroductionInvestigating coronary microvascular perfusion responses after myocardial infarction (MI) would aid in the development of flow preserving therapies. Laser speckle contrast imaging (LSCI) is a powerful tool used for real-time, non-contact, full-field imaging of blood flow in various tissues/organs. However, its use in the beating heart has been limited due to motion artifacts.MethodsIn this paper, we report the novel use of LSCI, combined with custom speckle analysis software (SpAn), to visualise and quantitate changes in ventricular perfusion in adult and aged mice undergoing ischaemia-reperfusion (IR) injury. The therapeutic benefit of inhibiting the actions of the pro-inflammatory cytokine interleukin-36 (IL-36) was also investigated using an IL-36 receptor antagonist (IL-36Ra).ResultsImaging from uncovered and covered regions of the left ventricle demonstrated that whilst part of the LSCI flux signal was derived from beating motion, a significant contributor to the flux signal came from ventricular microcirculatory blood flow. We show that a biphasic flux profile corresponding to diastolic and systolic phases of the cardiac cycle can be detected without mathematically processing the total flux data to denoise motion artifacts. Furthermore, perfusion responses to ischaemia and postischaemia were strong, reproducible and could easily be detected without the need to subtract motion-related flux signals. LSCI also identified significantly poorer ventricular perfusion in injured aged mice following IR injury which markedly improved with IL-36Ra.DiscussionWe therefore propose that LSCI of the heart is possible despite motion artifacts and may facilitate future investigations into the role of the coronary microcirculation in cardiovascular diseases and development of novel therapies.
Grazing led to an increase in the root: shoot ratio and a shallow root system in an alpine meadow of the Tibetan plateau
Authors: Wang Duobin , Ding Wenqiang 
Published: February 2024

Grazing is a main land use of natural grasslands in the world, which has both positive and negative impact on plant community structure and ecosystem functioning. However, the effects of long-term grazing management on the plant–soil system, in particular above- and belowground community characteristics, are still not well understood in alpine meadow community. In this study, we investigated the vegetation, roots, and soil properties under three management types (16 years of fencing since 2004-2020, moderate grazing and heavy grazing managements) in an alpine meadow on the Tibetan Plateau. The results showed that, compared with moderate grazing meadows, long-term fencing increased plant community cover, above- and belowground biomass, proportion of grass and litter but reduced forbs and soil bulk density, which caused the increases in soil organic carbon, total nitrogen and water content and the decreases in soil pH. However, heavy grazing led to opposite changes in proportion of grass, community biomass and soil physicochemical properties. The maximum of species richness and plant density appeared in moderate grazing meadows, supporting the intermediate disturbance hypothesis, and it can maintain above- and belowground biomass and soil physicochemical properties at medium level. Grazing increased the root: shoot ratio and caused root system shallow, which is consistent with the optimal partitioning hypothesis. Overall, our study suggested that moderate grazing is a more reasonable grazing management for sustainable development in alpine meadows of Tibetan Plateau, fencing could be an effective management strategy for vegetation restoration as well as for nutrient sequestration in degraded grasslands, but long-term fencing dose not benefit for biodiversity maintenance.
Comprehensive design and analysis of a 300L steel fuel tank for heavy off-road vehicles: numerical and experimental insights
Authors: Verma Aditya , Shankar Ravi , Malik Shaik Ameer , Veera Siva Reddy B. , Chandrasekhara Sastry C. , Shaik Nizmi , Salunkhe Sachin , Cep Robert , Abouel Nasr Emad 
Published: February 2024

Introduction: This study presents a comprehensive design and analysis of a 300L steel fuel tank intended for heavy off-road vehicles. The design process integrates numerical simulations and experimental investigations to optimize the tank's performance and durability under various operating conditions.Methods: The design methodology involves CAD model optimization, numerical analysis setup, and experimental validation. CAD model optimization simplifies the tank geometry while retaining structural integrity. Numerical analysis setup includes defining boundary conditions, meshing strategies, and simulation parameters. Experimental validation entails testing the tank under dynamic loading conditions to assess its structural response.Results: Numerical simulations reveal insights into stress distribution, deformation behavior, and fluid dynamics within the tank. Experimental tests confirm the numerical predictions and provide valuable data for model validation. Key results include stress concentrations in critical areas, deformation patterns under different loading conditions, and fluid flow characteristics.Discussion: The integrated approach combining numerical simulations and experimental tests offers a comprehensive understanding of the fuel tank's behavior. Findings highlight areas for design improvement, such as reinforcement of stress-prone regions and optimization of fluid flow dynamics. The study contributes to enhancing the performance, reliability, and safety of fuel tanks for heavy off-road vehicles.
Detecting and identifying pathogens and antagonistic bacteria associated with Ginkgo biloba leaf spot disease
Authors: Shen Huoyun , Li Xiyang , Li Zilong 
Published: February 2024

BackgroundLeaf spot disease severely impacts Ginkgo biloba (G. biloba) yield and quality. While microbial agents offer effective and non-toxic biological control for plant diseases, research on controlling leaf spot disease in G. biloba is notably scarce.MethodsThe pathogenic fungi were isolated and purified from diseased and healthy leaves of G. biloba, Subsequent examinations included morphological observations and molecular identification via PCR techniques. A phylogenetic tree was constructed to facilitate the analysis of these pathogenic fungi, and Koch’s postulates were subsequently employed to reaffirm their pathogenic nature. The antagonistic experiment was employed to select biocontrol bacteria, and subsequently, the isolated biocontrol bacteria and pathogenic fungi were inoculated onto healthy leaves to assess the inhibitory effects of the biocontrol bacteria.ResultsTwo pathologies responsible for the leaf spot disease on G. biloba were identified as Botryosphaeria dothidea and Neofusicoccum parvum via the analysis of phylogenetic tree and the application of Koch’s Postulates. Additionally, we isolated two strains of biocontrol bacteria, namely Bacillus velezensis and Bacillus amyloliquefaciens. Their average inhibitory zones were measured at 4.78 cm and 3.46 cm, respectively. The inhibition zone of B. velezensis against N. parvum was 4 cm. B. velezensis showed a stronger inhibitory effect compared to B. amyloliquefaciens on the development of lesions caused by B. dothidea via leaf culture experiment.ConclusionThis research reports, for the first time, the presence of B. dothidea as a pathogenic fungus affecting G. biloba. Moreover, the biocontrol bacteria, B. velezensis and B. amyloliquefaciens, exhibited the capability to effectively inhibit the growth and reproduction of B. dothidea, indicating their promising potential as environmentally friendly biocontrol resources.
Identification of the KIF18A alpha-4 helix as a therapeutic target for chromosomally unstable tumor cells
Authors: Schutt Katherine L. , Queen Katelyn A. , Fisher Kira , Budington Olivia , Mao Weifeng , Liu Wei , Gu Xiaohui , Xiao Yisong , Aswad Fred , Joseph James , Stumpff Jason 
Published: February 2024

Background: The mitotic kinesin, KIF18A, is required for proliferation of cancer cells that exhibit chromosome instability (CIN), implicating it as a promising target for treatment of a subset of aggressive tumor types. Determining regions of the KIF18A protein to target for inhibition will be important for the design and optimization of effective small molecule inhibitors.Methods: In this study, we used cultured cell models to investigate the effects of mutating S284 within the alpha-4 helix of KIF18A, which was previously identified as a phosphorylated residue.Results: Mutations in S284 cause relocalization of KIF18A from the plus-ends of spindle microtubules to the spindle poles. Furthermore, KIF18A S284 mutants display loss of KIF18A function and fail to support proliferation in CIN tumor cells. Interestingly, similar effects on KIF18A localization and function were seen after treatment of CIN cells with KIF18A inhibitory compounds that are predicted to interact with residues within the alpha-4 helix.Conclusion: These data implicate the KIF18A alpha-4 helix as an effective target for inhibition and demonstrate that small molecules targeting KIF18A selectively limit CIN tumor cell proliferation and result in phenotypically similar effects on mitosis at the single cell level compared to genetic perturbations.
Repetitive transcranial magnetic stimulation regulates effective connectivity patterns of brain networks in the spectrum of preclinical Alzheimer’s disease
Authors: Liang Xuhong , Xue Chen , Zheng Darui , Yuan Qianqian , Qi Wenzhang , Ruan Yiming , Chen Shanshan , Song Yu , Wu Huimin , Lu Xiang , Xiao Chaoyong , Chen Jiu 
Published: February 2024

ObjectivesSubjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) are considered as the spectrum of preclinical Alzheimer’s disease (AD), with abnormal brain network connectivity as the main neuroimaging feature. Repetitive transcranial magnetic stimulation (rTMS) has been proven to be an effective non-invasive technique for addressing neuropsychiatric disorders. This study aims to explore the potential of targeted rTMS to regulate effective connectivity within the default mode network (DMN) and the executive control network (CEN), thereby improving cognitive function.MethodsThis study included 86 healthy controls (HCs), 72 SCDs, and 86 aMCIs. Among them, 10 SCDs and 11 aMCIs received a 2-week rTMS course of 5-day, once-daily. Cross-sectional analysis with the spectral dynamic causal model (spDCM) was used to analyze the DMN and CEN effective connectivity patterns of the three groups. Afterwards, longitudinal analysis was conducted on the changes in effective connectivity patterns and cognitive function before and after rTMS for SCD and aMCI, and the correlation between them was analyzed.ResultsCross-sectional analysis showed different effective connectivity patterns in the DMN and CEN among the three groups. Longitudinal analysis showed that the effective connectivity pattern of the SCD had changed, accompanied by improvements in episodic memory. Correlation analysis indicated a negative relationship between effective connectivity from the left angular gyrus (ANG) to the anterior cingulate gyrus and the ANG.R to the right middle frontal gyrus, with visuospatial and executive function, respectively. In patients with aMCI, episodic memory and executive function improved, while the effective connectivity pattern remained unchanged.ConclusionThis study demonstrates that PCUN-targeted rTMS in SCD regulates the abnormal effective connectivity patterns in DMN and CEN, thereby improving cognition function. Conversely, in aMCI, the mechanism of improvement may differ. Our findings further suggest that rTMS is more effective in preventing or delaying disease progression in the earlier stages of the AD spectrum.Clinical Trial Registrationhttp://www.chictr.org.cn, ChiCTR2000034533.
How to assess the accuracy of volume conduction models? A validation study with stereotactic EEG data
Authors: Piastra Maria Carla , Oostenveld Robert , Homölle Simon , Han Biao , Chen Qi , Oostendorp Thom 
Published: February 2024

IntroductionVolume conduction models of the human head are used in various neuroscience fields, such as for source reconstruction in EEG and MEG, and for modeling the effects of brain stimulation. Numerous studies have quantified the accuracy and sensitivity of volume conduction models by analyzing the effects of the geometrical and electrical features of the head model, the sensor model, the source model, and the numerical method. Most studies are based on simulations as it is hard to obtain sufficiently detailed measurements to compare to models. The recording of stereotactic EEG during electric stimulation mapping provides an opportunity for such empirical validation.MethodsIn the study presented here, we used the potential distribution of volume-conducted artifacts that are due to cortical stimulation to evaluate the accuracy of finite element method (FEM) volume conduction models. We adopted a widely used strategy for numerical comparison, i.e., we fixed the geometrical description of the head model and the mathematical method to perform simulations, and we gradually altered the head models, by increasing the level of detail of the conductivity profile. We compared the simulated potentials at different levels of refinement with the measured potentials in three epilepsy patients.ResultsOur results show that increasing the level of detail of the volume conduction head model only marginally improves the accuracy of the simulated potentials when compared to in-vivo sEEG measurements. The mismatch between measured and simulated potentials is, throughout all patients and models, maximally 40 microvolts (i.e., 10% relative error) in 80% of the stimulation-recording combination pairs and it is modulated by the distance between recording and stimulating electrodes.DiscussionOur study suggests that commonly used strategies used to validate volume conduction models based solely on simulations might give an overly optimistic idea about volume conduction model accuracy. We recommend more empirical validations to be performed to identify those factors in volume conduction models that have the highest impact on the accuracy of simulated potentials. We share the dataset to allow researchers to further investigate the mismatch between measurements and FEM models and to contribute to improving volume conduction models.
Exploration of potential biomarkers for early bladder cancer based on urine proteomics
Authors: Zhou Xu , Xue Fei , Li Tingmiao , Xue Jiangshan , Yue Siqi , Zhao Shujie , Lu Hezhen , He Chengyan 
Published: February 2024

BackgroundBladder cancer is a common malignant tumor of the urinary system. The progression of the condition is associated with a poor prognosis, so it is necessary to identify new biomarkers to improve the diagnostic rate of bladder cancer.MethodsIn this study, 338 urine samples (144 bladder cancer, 123 healthy control, 32 cystitis, and 39 upper urinary tract cancer samples) were collected, among which 238 samples (discovery group) were analyzed by LC−MS. The urinary proteome characteristics of each group were compared with those of bladder cancer, and the differential proteins were defined by bioinformatics analysis. The pathways and functional enrichments were annotated. The selected proteins with the highest AUC score were used to construct a diagnostic panel. One hundred samples (validation group) were used to test the effect of the panel by ELISA.ResultsCompared with the healthy control, cystitis and upper urinary tract cancer samples, the number of differential proteins in the bladder cancer samples was 325, 158 and 473, respectively. The differentially expressed proteins were mainly related to lipid metabolism and iron metabolism and were involved in the proliferation, metabolism and necrosis of bladder cancer cells. The AUC of the panel of APOL1 and ITIH3 was 0.96 in the discovery group. ELISA detection showed an AUC of 0.92 in the validation group.ConclusionThis study showed that urinary proteins can reflect the pathophysiological changes in bladder cancer and that important molecules can be used as biomarkers for bladder cancer screening. These findings will benefit the application of the urine proteome in clinical research.