bluuebunny/crossref_metadata_2025 huggingface dataset:
Unveiling the microbiota-metabolite-myocardium axis: a novel perspective on cardiovascular health
Authors: Guo Zhenhua , Zhong Yangfang , Zhou Le , Xu Peier , Gao Naijing , Lu Jinyue , Yan Xueyun , Cao Huaming
Published: May 2024

Introduction

Cardiovascular diseases, including myocardial infarction, remain a leading cause of death globally. Emerging evidence suggests the gut microbiota plays a crucial role in cardiovascular health. This study aims to explore the impact of gut microbiota on myocardial infarction using a mouse model.

Methods

The research utilizes a multi-omics approach, including 16S rDNA sequencing and LC-MS-based metabolomics to analyze fecal and serum samples from mice modeled to mimic myocardial infarction. This methodology allows for a comprehensive analysis of microbial populations and their metabolic output.

Results

The findings reveal a significant reduction in gut microbiota α-diversity in mice with induced myocardial infarction compared to healthy controls. Notably, there is an increase in populations of Fusobacteria and Clostridia. Metabolomic analysis indicates disruptions in amino acid and energy metabolism, suggesting a metabolic dysregulation linked to myocardial health.

Discussion

The study proposes a novel microbiota-metabolite-myocardium axis, where specific microbial metabolites may directly affect heart health. This connection points to the gut microbiota as a potential player in the pathogenesis of myocardial infarction and may open new therapeutic avenues targeting the gut microbiome to combat cardiovascular diseases.
CpSmt3, an ortholog of small ubiquitin-like modifier, is essential for growth, organelle function, virulence, and antiviral defense in Cryphonectria parasitica
Authors: Li Shuangcai , Chen Fengyue , Wei Xiangyu , Yuan Luying , Qin Jiayao , Li Ru , Chen Baoshan
Published: May 2024

Introduction

SUMOylation is an important post-translational modification that regulates the expression, localization, and activity of substrate proteins, thereby participating in various important cellular processes such as the cell cycle, cell metabolism, gene transcription, and antiviral activity. However, the function of SUMOylation in phytopathogenic fungi has not yet been adequately explored.

Methods

A comprehensive analysis composed of proteomics, affinity pull-down, molecular and cellular approaches was performed to explore the roles of SUMOylation in Cryphonectria parasitica, the fungal pathogen responsible for chestnut blight.

Results and discussion

CpSmt3, the gene encoding the SUMO protein CpSmt3 in C. parasitica was identified and characterized. Deletion of the CpSmt3 gene resulted in defects in mycelial growth and hyphal morphology, suppression of sporulation, attenuation of virulence, weakening of stress tolerance, and elevated accumulation of hypovirus dsRNA. The ΔCpSmt3 deletion mutant exhibited an increase in mitochondrial ROS, swollen mitochondria, excess autophagy, and thickened cell walls. About 500 putative SUMO substrate proteins were identified by affinity pull-down, among which many were implicated in the cell cycle, ribosome, translation, and virulence. Proteomics and SUMO substrate analyses further revealed that deletion of CpSmt3 reduced the accumulation of CpRho1, an important protein that is involved in TOR signal transduction. Silencing of CpRho1 resulted in a phenotype similar to that of ΔCpSmt3, while overexpression of CpRho1 could partly rescue some of the prominent defects in ΔCpSmt3. Together, these findings demonstrate that SUMOylation by CpSmt3 is vitally important and provide new insights into the SUMOylation-related regulatory mechanisms in C. parasitica.
Effect of high sodium ion level on the interaction of AmB with a cholesterol-rich phospholipid monolayer
Authors: Wang Juan , Qiang Jiahao , Li Jinzi , Wang Dengwu
Published: May 2024

Invasive fungal infections are a primary reason for high mortality in immunocompromised people, especially in critically ill patients, such as intensive care unit (ICU) patients, advanced cancer patients, or severe burn patients. Hypernatremia also can increase mortality in severely ill patients. Amphotericin B (AmB) is the gold standard for treating infections, but in severely ill patients, AmB can cause hematotoxicity when administered intravenously due to its interaction with cholesterol on red blood cell membranes. This results in limited doses of AmB and affects the treatment of infections. The proportion of cholesterol molecules in membrane lipids in red blood cells is as high as 50 mol%, and the sodium ions can influence the interaction between AmB and lipids on the membrane. Therefore, in the complex clinical situation of a severely ill patient with a fungal infection and hypernatremia, the interaction between amphotericin B and the red blood cell membranes is worth studying in depth. In this work, the interaction between AmB and the dipalmitoyl phosphatidylcholine (DPPC)/cholesterol mixed monolayer in the presence of high sodium ion levels was studied when the proportion of cholesterol was 50%. The results show that the effect of AmB on reducing the monolayer’s area at a high level of sodium ions is slightly stronger at 30 mN/m. The effect of AmB on reducing the elastic modulus of the DPPC/Chol monolayer is significantly weakened by a high sodium ion level, compared with the level of sodium ions at normal physiological concentration. The higher the sodium ion concentration, the weaker the intermolecular force of the DPPC/Chol/AmB mixed monolayers. The scanning electron microscope (SEM) and atomic force microscopy (AFM) observations suggest that at a high sodium ion level, the presence of AmB significantly reduces the surface roughness of the DPPC/Chol monolayer. AmB may bind to cholesterol molecules, and it isolates cholesterol from the monolayer, resulting in a reduced height of the cholesterol-rich monolayer and an increasingly dispersed monolayer region. The results are beneficial to understanding the mechanism of impact of a high sodium ion level on the relationship between AmB and red blood cell membranes rich in cholesterol and are valuable for understanding the hemolytic toxicity of AmB to red blood cells at a high sodium ion level.
Deep learning for automatic segmentation of vestibular schwannoma: a retrospective study from multi-center routine MRI
Authors: Kujawa Aaron , Dorent Reuben , Connor Steve , Thomson Suki , Ivory Marina , Vahedi Ali , Guilhem Emily , Wijethilake Navodini , Bradford Robert , Kitchen Neil , Bisdas Sotirios , Ourselin Sebastien , Vercauteren Tom , Shapey Jonathan
Published: May 2024

Automatic segmentation of vestibular schwannoma (VS) from routine clinical MRI has potential to improve clinical workflow, facilitate treatment decisions, and assist patient management. Previous work demonstrated reliable automatic segmentation performance on datasets of standardized MRI images acquired for stereotactic surgery planning. However, diagnostic clinical datasets are generally more diverse and pose a larger challenge to automatic segmentation algorithms, especially when post-operative images are included. In this work, we show for the first time that automatic segmentation of VS on routine MRI datasets is also possible with high accuracy. We acquired and publicly release a curated multi-center routine clinical (MC-RC) dataset of 160 patients with a single sporadic VS. For each patient up to three longitudinal MRI exams with contrast-enhanced T1-weighted (ceT1w) (n = 124) and T2-weighted (T2w) (n = 363) images were included and the VS manually annotated. Segmentations were produced and verified in an iterative process: (1) initial segmentations by a specialized company; (2) review by one of three trained radiologists; and (3) validation by an expert team. Inter- and intra-observer reliability experiments were performed on a subset of the dataset. A state-of-the-art deep learning framework was used to train segmentation models for VS. Model performance was evaluated on a MC-RC hold-out testing set, another public VS datasets, and a partially public dataset. The generalizability and robustness of the VS deep learning segmentation models increased significantly when trained on the MC-RC dataset. Dice similarity coefficients (DSC) achieved by our model are comparable to those achieved by trained radiologists in the inter-observer experiment. On the MC-RC testing set, median DSCs were 86.2(9.5) for ceT1w, 89.4(7.0) for T2w, and 86.4(8.6) for combined ceT1w+T2w input images. On another public dataset acquired for Gamma Knife stereotactic radiosurgery our model achieved median DSCs of 95.3(2.9), 92.8(3.8), and 95.5(3.3), respectively. In contrast, models trained on the Gamma Knife dataset did not generalize well as illustrated by significant underperformance on the MC-RC routine MRI dataset, highlighting the importance of data variability in the development of robust VS segmentation models. The MC-RC dataset and all trained deep learning models were made available online.
Meta-analysis of the efficacy of Jingjin acupuncture therapy in the treatment of spastic cerebral palsy
Authors: Kang Xingyu , Huang Ying , Zheng Yi , Zhang Qian , Gong Rui , Tan Jinlang , Ma Le , Chen Siyu , Lv Xueyan , Shi Shuai
Published: May 2024

Background

This study aimed to systematically evaluate the clinical efficacy of Jingjin (muscle region of the meridian, sinew/tendon/fascia) acupuncture therapy for the treatment of spastic cerebral palsy.

Methods

Computer searches of the Cochrane Library, Web of Science, PubMed, Embase, Chinese Biomedical Literature (CBM) Database, Wanfang database, Wipu (VIP) database, and China National Knowledge Infrastructure (CNKI) database for published randomized controlled trial (RCT) studies on Jingjin acupuncture treatment of cerebral palsy from the beginning of the database construction until 30 November 2023 were performed, and the quality of the papers was assessed through independent data extraction by two individuals and then meta-analyzed using RevMan5.4 software. A total of 20 RCTs involving 1,453 patients were included.

Results

The overall effective rate of Jingjin acupuncture therapy was better than that of conventional therapy, with a combined odds ratio (OR) of 4.70 and a 95% confidence interval (CI) of [3.05, 7.24]. The Modified Ashworth Spasticity (MAS) Scale, Gross Motor Function Measure (GMFM), Fine Motor Function Measure (FMFM), and Comprehensive Spasticity Scale (CSS) scores are superior to conventional therapy.

Conclusion

Jingjin acupuncture therapy is effective in treating spastic cerebral palsy and has better overall efficacy than conventional therapy. Due to the low quality of some of the literature in this study type, more high-quality, well-designed clinical studies are needed to validate it.
Association between human blood metabolites and cerebral cortex architecture: evidence from a Mendelian randomization study
Authors: Jiang Zongzhi , Sun Yining , Liu Songyan
Published: May 2024

Background

Dysregulation of circulating metabolites may affect brain function and cognition, associated with alterations in the cerebral cortex architecture. However, the exact cause remains unclear. This study aimed to determine the causal effect of circulating metabolites on the cerebral cortex architecture.

Methods

This study utilized retrieved data from genome-wide association studies to investigate the relationship between blood metabolites and cortical architecture. A total of 1,091 metabolites and 309 metabolite ratios were used for exposure. The brain cortex surface area and cortex thickness were selected as the primary outcomes in this study. In this study, the inverse variance weighting method was used as the main analytical method, complemented by sensitivity analyses that were more robust to pleiotropy. Furthermore, metabolic pathway analysis was performed via MetaboAnalyst 6.0. Finally, reverse Mendelian randomization (MR) analysis was conducted to assess the potential for reverse causation.

Results

After correcting for the false discovery rate (FDR), we identified 37 metabolites and 9 metabolite ratios that showed significant causal associations with cortical structures. Among these, Oxalate was found to be most strongly associated with cortical surface area (β: 2387.532, 95% CI 756.570–4018.495, p = 0.037), while Tyrosine was most correlated with cortical thickness (β: −0.015, 95% CI −0.005 to −0.025, p = 0.025). Furthermore, pathway analysis based on metabolites identified six significant metabolic pathways associated with cortical structures and 13 significant metabolic pathways based on metabolite ratios.

Conclusion

The identified metabolites and relevant metabolic pathways reveal potential therapeutic pathways for reducing the risk of neurodegenerative diseases. These findings will help guide health policies and clinical practice in treating neurodegenerative diseases.
A case report: Gliosarcoma associated with a germline heterozygous mutation in MSH2
Authors: Wang Yuhan , Zhang Zhiyuan
Published: May 2024

Gliosarcoma is a rare subtype of glioblastoma (GBM) with a shorter medical history and a worse prognosis compared to other Grade 4 gliomas. Most gliosarcomas are sporadic, but it is undeniable that a small percentage are linked to germline mutations and several inherited cancer susceptibility syndromes, including Lynch Syndrome (LS). The authors present a case of a primary mismatch repair-deficient gliosarcoma in LS. A 54-year-old Chinese male patient was admitted to the hospital with a history of facial asymmetry for over 1 month and right temporo-occipital pain for 5 days. Head MRI revealed a complex mass lesion in the right frontoparietal region, consisting of cystic and solid components. The patient’s history of colon malignancy and family history of rectal carcinoma were noteworthy. Postoperative pathology indicated the presence of gliosarcoma with high-frequency microsatellite instability (MSI-H) and mismatch repair deficiency (MMRD). Further genetic testing results confirmed a germline heterozygous mutation in MSH2, which is considered the gold standard for diagnosing LS. This case report enriches the existing literature on germline MSH2 mutations and gliosarcomas. It highlights the importance for neurosurgeons to consider possible hereditary disorders when treating patients with a history of concurrent tumors outside the nervous system. Genetic testing is crucial for further identification of such disorders.
3D inversion recovery ultrashort echo time MRI can detect demyelination in cuprizone-treated mice
Authors: Searleman Adam C. , Ma Yajun , Sampath Srihari , Sampath Srinath , Bussell Robert , Chang Eric Y. , Deaton Lisa , Schumacher Andrew M. , Du Jiang
Published: May 2024

Purpose

To test the ability of inversion-recovery ultrashort echo time (IR-UTE) MRI to directly detect demyelination in mice using a standard cuprizone mouse model.

Methods

Non-aqueous myelin protons have ultrashort T2s and are “invisible” with conventional MRI sequences but can be detected with UTE sequences. The IR-UTE sequence uses an adiabatic inversion-recovery preparation to suppress the long T2 water signal so that the remaining signal is from the ultrashort T2 myelin component. In this study, eight 8-week-old C57BL/6 mice were fed cuprizone (n = 4) or control chow (n = 4) for 5 weeks and then imaged by 3D IR-UTE MRI. The differences in IR-UTE signal were compared in the major white matter tracts in the brain and correlated with the Luxol Fast Blue histochemical marker of myelin.

Results

IR-UTE signal decreased in cuprizone-treated mice in white matter known to be sensitive to demyelination in this model, such as the corpus callosum, but not in white matter known to be resistant to demyelination, such as the internal capsule. These findings correlated with histochemical staining of myelin content.

Conclusions

3D IR-UTE MRI was sensitive to cuprizone-induced demyelination in the mouse brain, and is a promising noninvasive method for measuring brain myelin content.
Heart rate variability as a preictal marker for determining the laterality of seizure onset zone in frontal lobe epilepsy
Authors: Lee Seho , Kim Hayom , Kim Jin Hyung , So Mingyeong , Kim Jung Bin , Kim Dong-Joo
Published: May 2024

Determining the laterality of the seizure onset zone is challenging in frontal lobe epilepsy (FLE) due to the rapid propagation of epileptic discharges to the contralateral hemisphere. There is hemispheric lateralization of autonomic control, and heart rate is modulated by interactions between the sympathetic and parasympathetic nervous systems. Based on this notion, the laterality of seizure foci in FLE might be determined using heart rate variability (HRV) parameters. We explored preictal markers for differentiating the laterality of seizure foci in FLE using HRV parameters. Twelve patients with FLE (6 right FLE and 6 left FLE) were included in the analyzes. A total of 551 (460 left FLE and 91 right FLE) 1-min epoch electrocardiography data were used for HRV analysis. We found that most HRV parameters differed between the left and right FLE groups. Among the machine learning algorithms applied in this study, the light gradient boosting machine was the most accurate, with an AUC value of 0.983 and a classification accuracy of 0.961. Our findings suggest that HRV parameter-based laterality determination models can be convenient and effective tools in clinical settings. Considering that heart rate can be easily measured in real time with a wearable device, our proposed method can be applied to a closed-loop device as a real-time monitoring tool for determining the side of stimulation.
Association between serum potassium and Parkinson’s disease in the US (NHANES 2005–2020)
Authors: Zhou Xue , Zhao Jingtong , Liu Yang , Sun Xiaozhou , Li Xuefeng , Ren Jixiang , Li Qingjie , Han Dong , Pan Ting , Shi Yingqi , Wu Dalong , Chen Xinhua
Published: May 2024

Background

Evaluating the correlation between serum potassium and Parkinson’s disease (PD) in US adults.

Methods

A cross-sectional study was conducted on 20,495 adults aged 40 years or older using NHANES data from 2005 to 2020. The study utilized one-way logistic regression and multifactorial logistic regression to examine the correlation between serum potassium levels and PD. Additionally, a smoothed curve fitting approach was employed to assess the concentration-response relationship between serum potassium and PD. Stratified analyses were carried out to investigate potential interactions between serum potassium levels and PD with variables such as age, sex, race, marital status, education, BMI, smoking and medical conditions like coronary, stroke, diabetes, hypertension, and hypercholesterolemia.

Results

In this study, a total of 20,495 participants, comprising 403 PD and 20,092 non-PD individuals, were included. After adjusted for covariates, multivariable logistic regression revealed that high serum potassium level was an independent risk factor for PD (OR:1.86, 95% CI:1.45 ~ 2.39, p < 0.01).The linear association between serum potassium and PD was described using fitted smoothing curves. Age, sex, race, education, marital, BMI, coronary, stroke, diabetes, hypertension and hypercholesterolemia were not significantly correlated with this positive connection, according to subgroup analysis and interaction testing (P for interaction >0.05).

Conclusion

Serum potassium levels are elevated in patients with Parkinson's disease compared to non-PD patients. Additional prospective studies are required to explore the significance of serum potassium levels in individuals with Parkinson's disease.
GnRH peripherally modulates nociceptor functions, exacerbating mechanical pain
Authors: Zheng Haiyan , Kim Minseok , Kim Chaeun , Kim Yerin , Cho Pyung Sun , Lim Ji Yeon , Lee Hojin , Yun Hye-In , Choi Jungmin , Hwang Sun Wook
Published: May 2024

The function of peripheral nociceptors, the neurons that relay pain signals to the brain, are frequently tuned by local and systemic modulator substances. In this context, neurohormonal effects are emerging as an important modulatory mechanism, but many aspects remain to be elucidated. Here we report that gonadotropin-releasing hormone (GnRH), a brain-specific neurohormone, can aggravate pain by acting on nociceptors in mice. GnRH and GnRHR, the receptor for GnRH, are expressed in a nociceptor subpopulation. Administration of GnRH and its analogue, localized for selectively affecting the peripheral neurons, deteriorated mechanical pain, which was reproducible in neuropathic conditions. Nociceptor function was promoted by GnRH treatment in vitro, which appears to involve specific sensory transient receptor potential ion channels. These data suggest that peripheral GnRH can positively modulate nociceptor activities in its receptor-specific manner, contributing to pain exacerbation. Our study indicates that GnRH plays an important role in neurohormonal pain modulation via a peripheral mechanism.
Mapping proteomic composition of excitatory postsynaptic sites in the cerebellar cortex
Authors: Robinson Kaylie , Delhaye Mathias , Craig Ann Marie
Published: May 2024

Functions of the cerebellar cortex, from motor learning to emotion and cognition, depend on the appropriate molecular composition at diverse synapse types. Glutamate receptor distributions have been partially mapped using immunogold electron microscopy. However, information is lacking on the distribution of many other components, such as Shank2, a postsynaptic scaffolding protein whose cerebellar dysfunction is associated with autism spectrum disorders. Here, we used an adapted Magnified Analysis of the Proteome, an expansion microscopy approach, to map multiple glutamate receptors, scaffolding and signaling proteins at single synapse resolution in the cerebellar cortex. Multiple distinct synapse-selective distribution patterns were observed. For example, AMPA receptors were most concentrated at synapses on molecular layer interneurons and at climbing fiber synapses, Shank1 was most concentrated at parallel fiber synapses on Purkinje cells, and Shank2 at both climbing fiber and parallel fiber synapses on Purkinje cells but little on molecular layer interneurons. Our results are consistent with gene expression data but also reveal input-selective targeting within Purkinje cells. In specialized glomerular structures of the granule cell layer, AMPA receptors as well as most other synaptic components preferentially targeted to synapses. However, NMDA receptors and the synaptic GTPase activating protein SynGAP preferentially targeted to extrasynaptic sites. Thus, glomeruli may be considered integrative signaling units through which mossy fibers differentially activate synaptic AMPA and extrasynaptic NMDA receptor complexes. Furthermore, we observed NMDA receptors and SynGAP at adherens junctions, suggesting a role in structural plasticity of glomeruli. Altogether, these data contribute to mapping the cerebellar ‘synaptome’.
rdHSV-CA8 non-opioid analgesic gene therapy decreases somatosensory neuronal excitability by activating Kv7 voltage-gated potassium channels
Authors: Kandel Munal B. , Zhuang Gerald Z. , Goins William F. , Marzulli Marco , Zhang Mingdi , Glorioso Joseph C. , Kang Yuan , Levitt Alexandra E. , Kwok Wai-Meng , Levitt Roy C. , Sarantopoulos Konstantinos D.
Published: May 2024

Chronic pain is common and inadequately treated, making the development of safe and effective analgesics a high priority. Our previous data indicate that carbonic anhydrase-8 (CA8) expression in dorsal root ganglia (DRG) mediates analgesia via inhibition of neuronal ER inositol trisphosphate receptor-1 (ITPR1) via subsequent decrease in ER calcium release and reduction of cytoplasmic free calcium, essential to the regulation of neuronal excitability. This study tested the hypothesis that novel JDNI8 replication-defective herpes simplex-1 viral vectors (rdHSV) carrying a CA8 transgene (vHCA8) reduce primary afferent neuronal excitability. Whole-cell current clamp recordings in small DRG neurons showed that vHCA8 transduction caused prolongation of their afterhyperpolarization (AHP), an essential regulator of neuronal excitability. This AHP prolongation was completely reversed by the specific Kv7 channel inhibitor XE-991. Voltage clamp recordings indicate an effect via Kv7 channels in vHCA8-infected small DRG neurons. These data demonstrate for the first time that vHCA8 produces Kv7 channel activation, which decreases neuronal excitability in nociceptors. This suppression of excitability may translate in vivo as non-opioid dependent behavioral- or clinical analgesia, if proven behaviorally and clinically.
CAD and constructive solid geometry modeling of the Molten Salt Reactor Experiment with OpenMC
Authors: Yilmaz Seda , Romano Paul K. , Chierici Lorenzo , Knudsen Erik B. , Shriwise Patrick C.
Published: May 2024

In this study, we present a detailed comparison of two independently developed models of the Molten Salt Reactor Experiment (MSRE) for Monte Carlo particle transport simulations: the constructive solid geometry (CSG) model that was developed in support of the MSRE benchmark in the International Handbook of Evaluated Reactor Physics Benchmark Experiments, and a CAD model that was developed by Copenhagen Atomics. The original Serpent reference CSG model was first converted to OpenMC’s input format so that it could be systematically compared to the CAD model, which was already available as an OpenMC model, using the same Monte Carlo code. Results from simulations using the Serpent and OpenMC CSG models showed that keff agreed within 10 pcm while the flux distribution in space and energy generally agreed within 0.1%. Larger differences were observed between the OpenMC CAD and CSG models; notably, the keff computed for the CAD model was 1.00872, which is more than 1% lower than the value for the CSG model and much closer to experiment. Several areas of the reactor that were modeled differently in the CSG and CAD models were discussed and, in several cases, their impact on keff was quantified. Lastly, we compared the computational performance and memory usage between the CAD and CSG models. Simulation of the CSG model was found to be 1.4–2.3× faster than simulation of the CAD model based on the Embree ray tracer while using 4× less memory, highlighting the need for continued improvements in the CAD-based particle transport ecosystem. Finally, major performance degradation was observed for CAD-based simulations when using the MOAB ray tracer.
Clcn3 deficiency ameliorates high-fat diet-induced obesity and improves metabolism in mice
Authors: Duan Sirui , Li Bo , Cui Shiyu , Chen Yaoyao , He Ying , Fan Lihong
Published: May 2024

Objective

Obesity is defined as excess body fat and is a current health epidemic associated with increased risk for type 2 diabetes and cardiovascular disease. The ClC-3 chloride channel/antiporter, encoded by the Clcn3, is associated with some diseases, like carcinoma, nervous system diseases, and metabolic diseases. To verify the relationship between the Clcn3 and weight including metabolic changes, searching for a new target for metabolic therapy of obesity, we designed the experiment.

Methods

The mice were divided into 4 different groups: Clcn3+/+ mice + high-fat diet (HFD), Clcn3−/− mice + HFD, Clcn3+/+ mice + normal diet (ND), Clcn3−/− mice + ND, and fed for 16 weeks. After the glucose tolerance test and insulin tolerance test, peripheral blood and adipose tissues were collected. Moreover, we performed transcriptome sequencing for the epididymal white adipose tissue from Clcn3+/+ and Clcn3−/− mice with the high-fat diet. Western blotting verified the changes in protein levels of relevant metabolic genes.

Results

We found that the Clcn3−/− mice had lower body weight and visceral fat, refining glucose and lipid metabolism in HFD-induced mice, but had no effect in normal diet mice. RNA-seq and Western blotting indicated that Clcn3 deficiency may inhibit obesity through the AMPK-UCP1 axis.

Conclusion

Modulation of Clcn3 may provide an appealing therapeutic target for obesity and associated metabolic syndrome.
Therapeutic potential of berries in age-related neurological disorders
Authors: Norouzkhani Narges , Afshari Shaghayegh , Sadatmadani Sayedeh-Fatemeh , Mollaqasem Mohammad Mahdi , Mosadeghi Shakila , Ghadri Hani , Fazlizade Safa , Alizadeh Keyvan , Akbari Javar Pouyan , Amiri Hamidreza , Foroughi Elaheh , Ansari Arina , Mousazadeh Kourosh , Davany Bozorgmehr Abdullahzadeh , Akhtari kohnehshahri Ata , Alizadeh Alaleh , Dadkhah Parisa Alsadat , Poudineh Mohadeseh
Published: May 2024

Aging significantly impacts several age-related neurological problems, such as stroke, brain tumors, oxidative stress, neurodegenerative diseases (Alzheimer’s, Parkinson’s, and dementia), neuroinflammation, and neurotoxicity. Current treatments for these conditions often come with side effects like hallucinations, dyskinesia, nausea, diarrhea, and gastrointestinal distress. Given the widespread availability and cultural acceptance of natural remedies, research is exploring the potential effectiveness of plants in common medicines. The ancient medical system used many botanical drugs and medicinal plants to treat a wide range of diseases, including age-related neurological problems. According to current clinical investigations, berries improve motor and cognitive functions and protect against age-related neurodegenerative diseases. Additionally, berries may influence signaling pathways critical to neurotransmission, cell survival, inflammation regulation, and neuroplasticity. The abundance of phytochemicals in berries is believed to contribute to these potentially neuroprotective effects. This review aimed to explore the potential benefits of berries as a source of natural neuroprotective agents for age-related neurological disorders.
Assessing user perspectives on clinical pharmacogenomics consultation documentation: a user-centered evaluation
Authors: Desai Nina , Ravindra Namratha , Hall Bradley , Al Alshaykh Hana , Lemke Lauren , Eken Eda , Cicali Emily J. , Wiisanen Kristin , Cavallari Larisa H. , Nguyen Khoa A.
Published: May 2024

The University of Florida Health Precision Medicine Program plays a crucial role in delivering pharmacogenomics (PGx) result notes to providers who request PGx testing. Despite this, there is currently a lack of a formal assessment of provider needs and established best practice design principles to guide the ongoing development of PGx result notes. This study aims to enhance the content and format of the PGx consult note at UF Health by incorporating valuable feedback from healthcare providers. Through in-depth user sessions involving 11 participants, we evaluated the usability of our consult note template. While overall satisfaction with the content was noted, specific sections, including those addressing phenoconversion and the medication list, were identified for revision to enhance clarity based on insightful provider feedback.
Improving prediction of tacrolimus concentration using a combination of population pharmacokinetic modeling and machine learning in chinese renal transplant recipients
Authors: Wang Yu-Ping , Lu Xiao-Ling , Shao Kun , Shi Hao-Qiang , Zhou Pei-Jun , Chen Bing
Published: May 2024

Aims

The population pharmacokinetic (PPK) model-based machine learning (ML) approach offers a novel perspective on individual concentration prediction. This study aimed to establish a PPK-based ML model for predicting tacrolimus (TAC) concentrations in Chinese renal transplant recipients.

Methods

Conventional TAC monitoring data from 127 Chinese renal transplant patients were divided into training (80%) and testing (20%) datasets. A PPK model was developed using the training group data. ML models were then established based on individual pharmacokinetic data derived from the PPK basic model. The prediction performances of the PPK-based ML model and Bayesian forecasting approach were compared using data from the test group.

Results

The final PPK model, incorporating hematocrit and CYP3A5 genotypes as covariates, was successfully established. Individual predictions of TAC using the PPK basic model, postoperative date, CYP3A5 genotype, and hematocrit showed improved rankings in ML model construction. XGBoost, based on the TAC PPK, exhibited the best prediction performance.

Conclusion

The PPK-based machine learning approach emerges as a superior option for predicting TAC concentrations in Chinese renal transplant recipients.
Safety and efficacy evaluation of halicin as an effective drug for inhibiting intestinal infections
Authors: Zhang Maolu , Lin Shuqian , Han Lianquan , Zhang Jiaming , Liu Shaoning , Yang Xiuzhen , Wang Ruiming , Yang Xiaohui , Yi Yunpeng
Published: May 2024

Halicin, the first antibacterial agent discovered by artificial intelligence, exerts broad-spectrum antibacterial effects and has a unique structure. Our study found that halicin had a good inhibitory effect on clinical isolates of drug-resistant strains and Clostridium perfringens (C. perfringens). The safety of halicin was evaluated by acute oral toxicity, genotoxicity and subchronic toxicity studies. The results of acute toxicity test indicated that halicin, as a low-toxicity compound, had an LD50 of 2018.3 mg/kg. The results of sperm malformation, bone marrow chromosome aberration and cell micronucleus tests showed that halicin had no obvious genotoxicity. However, the results of the 90-day subchronic toxicity test indicated that the test rats exhibited weight loss and slight renal inflammation at a high dose of 201.8 mg/kg. Teratogenicity of zebrafish embryos showed that halicin had no significant teratogenicity. Analysis of intestinal microbiota showed that halicin had a significant effect on the intestinal microbial composition, but caused a faster recovery. Furthermore, drug metabolism experiments showed that halicin was poorly absorbed and quickly eliminated in vivo. Our study found that halicin had a good therapeutic effect on intestinal infection model of C. perfringens. These results show the feasibility of developing oral halicin as a clinical candidate drug for treating intestinal infections.
The therapeutic effect of traditional Chinese medicine on breast cancer through modulation of the Wnt/β-catenin signaling pathway
Authors: Li Hongkun , Li Jiawei , Zhang Yifan , Zhao Chengcheng , Ge Jun , Sun Yujiao , Fu Hui , Li Yingpeng
Published: May 2024

Breast cancer, the most prevalent malignant tumor among women globally, is significantly influenced by the Wnt/β-catenin signaling pathway, which plays a crucial role in its initiation and progression. While conventional chemotherapy, the standard clinical treatment, suffers from significant drawbacks like severe side effects, high toxicity, and limited prognostic efficacy, Traditional Chinese Medicine (TCM) provides a promising alternative. TCM employs a multi-targeted therapeutic approach, which results in fewer side effects and offers a high potential for effective treatment. This paper presents a detailed analysis of the therapeutic impacts of TCM on various subtypes of breast cancer, focusing on its interaction with the Wnt/β-catenin signaling pathway. Additionally, it explores the effectiveness of both monomeric and compound forms of TCM in the management of breast cancer. We also discuss the potential of establishing biomarkers for breast cancer treatment based on key proteins within the Wnt/β-catenin signaling pathway. Our aim is to offer new insights into the prevention and treatment of breast cancer and to contribute to the standardization of TCM.
Are the class 18 myosins Myo18A and Myo18B specialist sarcomeric proteins?
Authors: Horsthemke Markus , Arnaud Charles-Adrien , Hanley Peter J.
Published: May 2024

Initially, the two members of class 18 myosins, Myo18A and Myo18B, appeared to exhibit highly divergent functions, complicating the assignment of class-specific functions. However, the identification of a striated muscle-specific isoform of Myo18A, Myo18Aγ, suggests that class 18 myosins may have evolved to complement the functions of conventional class 2 myosins in sarcomeres. Indeed, both genes, Myo18a and Myo18b, are predominantly expressed in the heart and somites, precursors of skeletal muscle, of developing mouse embryos. Genetic deletion of either gene in mice is embryonic lethal and is associated with the disorganization of cardiac sarcomeres. Moreover, Myo18Aγ and Myo18B localize to sarcomeric A-bands, albeit the motor (head) domains of these unconventional myosins have been both deduced and biochemically demonstrated to exhibit negligible ATPase activity, a hallmark of motor proteins. Instead, Myo18Aγ and Myo18B presumably coassemble with thick filaments and provide structural integrity and/or internal resistance through interactions with F-actin and/or other proteins. In addition, Myo18Aγ and Myo18B may play distinct roles in the assembly of myofibrils, which may arise from actin stress fibers containing the α-isoform of Myo18A, Myo18Aα. The β-isoform of Myo18A, Myo18Aβ, is similar to Myo18Aα, except that it lacks the N-terminal extension, and may serve as a negative regulator through heterodimerization with either Myo18Aα or Myo18Aγ. In this review, we contend that Myo18Aγ and Myo18B are essential for myofibril structure and function in striated muscle cells, while α- and β-isoforms of Myo18A play diverse roles in nonmuscle cells.
Callous-unemotional behaviors and conduct problems in Chinese preschoolers: the moderating roles of surgency and gender
Authors: Zhu Jingjing , Shu Xin , Li Zhuyi , Li Yan
Published: May 2024

Introduction

Conduct problems in children are related to callous-unemotional (CU) behaviors. However, results of the relationships between CU behaviors and conduct problems among preschoolers mainly focused on Western countries, no studies have examined whether CU behaviors predict conduct problem in Chinese preschoolers. The primary objective of the current study therefore was to examine the associations between CU behaviors and conduct problems as well as the moderating effects of surgency and child gender in Chinese preschool children.

Methods

The present study randomly selected 2,154 children (1,043 boys, Mage = 56 months, SD = 10.47) from six kindergartens in Shanghai, People’s Republic of China. Mothers rated children’s surgency and teachers reported children’s CU behaviors and conduct problems.

Results

Results demonstrated that CU behaviors were positively associated with conduct problems. Surgency and child gender significantly moderated these associations. Specifically, CU behaviors were positively associated with conduct problems, with a stronger effect found for high levels of surgency. CU behaviors had a positive association with conduct problems, with a stronger effect found for boys.

Discussion

This study indicate that temperament and gender characteristics influence conduct problems in preschoolers who exhibit high levels of CU behaviors. As well, the findings emphasize the significance of considering the meaning and implication of CU behaviors in Chinese culture.
Personality and teachers’ burnout stress: exploring the digital competence as personal job resource in allied health institutions
Authors: Hussain Zawar , Chenmei Cai , Saeed Muhammad , Hassan Nazia , Chiragh Fiza
Published: May 2024

Introduction

Job burnout has severe consequences for teachers and students. This study aimed to measure the direct effects of personality traits on job burnout-stress syndrome among allied health educators. Furthermore, teachers’ digital competence was evaluated as a personal job resource for mitigating the negative impact of burnout.

Methods

This study examined direct relationships between work-related stress syndrome and personality traits, namely, extroversion, agreeableness, conscientiousness, emotional stability, and openness to experience. Data was collected from 334 allied health institution teachers through a self-reported questionnaire. Linear regression analysis was used to test for direct effects. Moderating effects were evaluated using Andrew F Hays PROCESS macro v2.16.3.

Results

All five personality traits had a significant negative relationship to burnout and teachers’ digital competence moderated the relationship between personality traits and burnout. This study’s findings provide evidence, that personality is significantly related to job burnout among allied health educators.

Conclusion

These empirical findings conclude that personality traits are related to burnout in the non-Western culture of Pakistan. Furthermore, teachers’ digital competence acts as a personal job resource and potential moderator in the current digital working environment. Therefore, future teachers should enrich their digital competencies for improved performance, and advanced digital competency courses should be included in their curriculum.
The impacts of learning motivation, emotional engagement and psychological capital on academic performance in a blended learning university course
Authors: Liu Yan , Ma Shuai , Chen Yue
Published: May 2024

Introduction

This study aims to explore the relationships among psychological capital, learning motivation, emotional engagement, and academic performance for college students in a blended learning environment.

Method

The research consists of two studies: Study 1 primarily focuses on validating, developing, revising, and analyzing the psychometric properties of the scale using factor analysis, while Study 2 employs structural equation modeling (SEM) to test the hypotheses of relationships of included variables and draw conclusions based on 745 data collected in a university in China.

Results

Findings revealed that intrinsic motivation, extrinsic motivation, emotional engagement, and psychological capital all impact academic performance. Extrinsic learning motivation has significant positive direct effects on intrinsic learning motivation, emotional engagement, and psychological capital. Intrinsic motivation mediates the relationship between extrinsic motivation and academic performance.

Discussion

In future blended learning practices, it is essential to cultivate students’ intrinsic learning motivation while maintaining a certain level of external learning motivation. It is also crucial to stimulate and maintain students’ emotional engagement, enhance their sense of identity and belonging, and recognize the role of psychological capital in learning to boost students’ confidence, resilience, and positive emotions.
Archetype symbols and altered consciousness: a study of shamanic rituals in the context of Jungian psychology
Authors: Sun Hang , Kim Eunyoung
Published: May 2024

The alteration of consciousness during shamanic rituals is both a physical and mystical phenomenon. It involves psychological and spiritual experiences. Through ritual practices, shamans can connect with archetype within the collective unconscious, utilizing trance-inducing techniques for “hallucinatory exploration”. This study surveyed 75 participants to investigate the impact of prototype symbols in Shamanistic rituals on participants’ consciousness states focusing on Jungian psychology’s concept of archetype. The results indicate that archetype symbols in shamanic rituals can significantly influence participants’ conscious state, leading them to experience a conscious dissolution of the self. Furthermore, archetype symbols have different effects at the stages of consciousness change. In particular, during the “Visionary Restructuralization” stage, archetype symbols, such as patterns, masks, totems and music, brought participants’ consciousness to a peak and caused significant changes to it. These findings suggest that the metaphoric function of archetype symbols plays a crucial role in rituals. Archetype symbols connect the individual to the collective unconscious through visual images and symbolic imagery. They prompt the participants to experience emotional resonances that transcend individual experiences and affect their state of consciousness.
Rhetorical strategies in Chinese and English talk show humor: a comparative analysis
Authors: Tianli Zhou , Chen Shiyue
Published: May 2024

Humor is a kind of cognitive psychology activity, and it is diverse among individuals. One of the main characteristics of talk shows is to produce humorous discourse to make the audience laugh; however, rare studies have made a deeper comparative investigation on the rhetorical strategies in different language humorous utterances. Therefore, the current study adopted a mixed method of sequential explanatory design to identify the types of rhetorical strategies in the monolog verbal humor of Chinese and English talk shows, examine their similarities and differences. Two hundred monolog samples from 2016 to 2022, which consisted of 100 monologs of Chinese talk shows (CTS) and 100 monologs of English talk shows (ETS), were downloaded from the internet as language corpus. Berger’s theory was adopted to identify the types of rhetorical strategies. Based on the obtained findings, this study found that both language talk show hosts use a variety type of rhetorical strategies to produce humorous discourse. The comparison of similarities and differences revealed that the most frequently used rhetorical strategies in both talk shows were almost similar (e.g., satire, exaggeration, facetiousness, and ridicule), but the percentage of usage of these various rhetorical strategies in both talk shows was slightly different. Interestingly, misunderstanding occurred 20 times in CTS but was not found in ETS. Meanwhile, simile and personification were used more often in ETS. Conclusively, this study contributes valuable insights on the use of different types of rhetorical strategies to create verbal humor in different language contexts.
Family language policy in a transnational family living in Finland: multilingual repertoire, language practices, and child agency
Authors: Nenonen Olga
Published: May 2024

Each multilingual transnational family is unique and thus deserves to be carefully studied in terms of its family language policy (FLP). Speaker-centered approaches can provide a deeper understanding of linguistic diversity in a multilingual setting. The studied Russian-Italian family is raising a multilingual boy (8:2) in Finland. The multilingual repertoire includes Russian, Italian, Finnish, English, and Hebrew. In this case-study, an ethnographic approach is used to explore the multilingual family repertoire by presenting their lived experiences and language practices. I discuss the FLP and child’s active role in shaping the family’s linguistic practices (child agency). The following methods were combined: semi-structured interviews, language background surveys, written diary entries, self-recordings of interactions in the family, and a language portrait that depicts the child’s multilingual repertoire. The interviews and other recordings were transcribed manually. The following research questions guided the study: (1) How do the family members describe their FLP? (2) How does the FLP evolve through everyday interactions (language practices)? (3) How does the child exercise his agency in the family setting? The results reveal that the family’s language practices follow predominantly an one person-one language (OPOL) strategy; consequently, the child speaks a different language with each parent. However, the analysis of the language ideologies reveals positive attitudes toward both multilingualism and all the languages in the family’s repertoire, which explains the multilingual practices having multiplicity and unexpectedness. FLP is shaping the family language practices. Evidence of language hierarchy can be explained by a number of family-external and family-internal social factors.