bluuebunny/crossref_metadata_2025 huggingface dataset:
Frequency set selection for multi-frequency steady-state visual evoked potential-based brain-computer interfaces
Authors: Mu Jing , Grayden David B. , Tan Ying , Oetomo Denny
Published: December 2022

Objective

Multi-frequency steady-state visual evoked potential (SSVEP) stimulation and decoding methods enable the representation of a large number of visual targets in brain-computer interfaces (BCIs). However, unlike traditional single-frequency SSVEP, multi-frequency SSVEP is not yet widely used. One of the key reasons is that the redundancy in the input options requires an additional selection process to define an effective set of frequencies for the interface. This study investigates systematic frequency set selection methods.

Methods

An optimization strategy based on the analysis of the frequency components in the resulting multi-frequency SSVEP is proposed, investigated and compared to existing methods, which are constructed based on the analysis of the stimulation (input) signals. We hypothesized that minimizing the occurrence of common sums in the multi-frequency SSVEP improves the performance of the interface, and that selection by pairs further increases the accuracy compared to selection by frequencies. An experiment with 12 participants was conducted to validate the hypotheses.

Results

Our results demonstrated a statistically significant improvement in decoding accuracy with the proposed optimization strategy based on multi-frequency SSVEP features compared to conventional techniques. Both hypotheses were validated by the experiments.

Conclusion

Performing selection by pairs and minimizing the number of common sums in selection by pairs are effective ways to select suitable frequency sets that improve multi-frequency SSVEP-based BCI accuracies.

Significance

This study provides guidance on frequency set selection in multi-frequency SSVEP. The proposed method in this study shows significant improvement in BCI performance (decoding accuracy) compared to existing methods in the literature.
Individual behavioral profiling as a translational approach to assess treatment efficacy in an animal model of post-traumatic stress disorder
Authors: Sarkar Ishita , Snippe-Strauss Maja , Tenenhaus Zamir Adi , Benhos Amir , Richter-Levin Gal
Published: December 2022

A major challenge in treating post-traumatic stress disorder (PTSD) continues to be the large variability in responsiveness to pharmacotherapy. Only 20–30% of patients experience total remission to a specific treatment, while others demonstrate either partial remission or no response. However, this heterogeneity in response to pharmacotherapy has not been adequately addressed in animal models, since these analyze the averaged group effects, ignoring the individual variability to treatment response, which seriously compromises the translation power of such models. Here we examined the possibility of employing an “individual behavioral profiling” approach, originally developed to differentiate between “affected” and “exposed-unaffected” individuals in an animal model of PTSD, to also enable dissociating “responders” or “non-responders” after SSRI (fluoxetine) treatment. Importantly, this approach does not rely on a group averaged response to a single behavioral parameter, but considers a cluster of behavioral parameters, to individually characterize an animal as either “responder” or “non-responder” to the treatment. The main variable to assess drug efficacy thus being the proportion of “responders” following treatment. Alteration in excitatory/inhibitory (E/I) balance has been proposed as being associated with stress-related psychopathology. Toward a functional proof of concept for our behaviorally-based characterization approach, we examined the expression patterns of α1 and α2 subunits of GABAA receptor, and GluN1 and GluN2A subunits of the NMDAR receptor in the ventral hippocampus, as well as electrophysiologically local circuit activity in the dorsal dentate gyrus (DG). We demonstrate that with both parameters, treatment “responders” differed from treatment “non-responders,” confirming the functional validity of the behavior-based categorization. The results suggest that the ability to respond to fluoxetine treatment may be linked to the ability to modulate excitation-inhibition balance in the hippocampus. We propose that employing the “individual behavioral profiling” approach, and the resultant novel variable of the proportion of “recovered” individuals following treatment, offers an effective translational tool to assess pharmacotherapy treatment efficacy in animal models of stress and trauma-related psychopathology.
Millimeter-wave radar object classification using knowledge-assisted neural network
Authors: Wang Yanhua , Han Chang , Zhang Liang , Liu Jianhu , An Qingru , Yang Fei
Published: December 2022

To improve the cognition and understanding capabilities of artificial intelligence (AI) technology, it is a tendency to explore the human brain learning processing and integrate brain mechanisms or knowledge into neural networks for inspiration and assistance. This paper concentrates on the application of AI technology in advanced driving assistance system. In this field, millimeter-wave radar is essential for elaborate environment perception due to its robustness to adverse conditions. However, it is still challenging for radar object classification in the complex traffic environment. In this paper, a knowledge-assisted neural network (KANN) is proposed for radar object classification. Inspired by the human brain cognition mechanism and algorithms based on human expertise, two kinds of prior knowledge are injected into the neural network to guide its training and improve its classification accuracy. Specifically, image knowledge provides spatial information about samples. It is integrated into an attention mechanism in the early stage of the network to help reassign attention precisely. In the late stage, object knowledge is combined with the deep features extracted from the network. It contains discriminant semantic information about samples. An attention-based injection method is proposed to adaptively allocate weights to the knowledge and deep features, generating more comprehensive and discriminative features. Experimental results on measured data demonstrate that KANN is superior to current methods and the performance is improved with knowledge assistance.
Single-cell transcriptome reveals diversity of Müller cells with different metabolic-mitochondrial signatures in normal and degenerated macula
Authors: Liu Bei , He Jiali , Zhong Ling , Huang Lulin , Gong Bo , Hu Jing , Qian Hao , Yang Zhenglin
Published: December 2022

Müller cell is the most abundant glial cell in mammalian retina, supporting the functions of photoreceptors and other retinal neurons via maintaining environmental homeostasis. In response to injury and/or neuronal degeneration, Müller cells undergo morphological and functional alternations, known as reactive gliosis documented in multiple retinal diseases, including age-related macular degeneration (AMD), retinitis pigmentosa, diabetic retinopathy, and traumatic retinal detachment. But the functional consequences of Müller glia cell reactivation or even the regulatory networks of the retinal gliosis are still controversial. In this study, we reveal different subpopulations of Müller cells with distinct metabolic-mitochondrial signatures by integrating single cell transcriptomic data from Early AMD patients and healthy donors. Our results show that a portion of Müller cells exhibits low mitochondrial DNA (mtDNA) expressions, reduced protein synthesis, impaired homeostatic regulation, decreased proliferative ability but enhanced proangiogenic function. Interestingly, the major alternation of Müller cells in Early AMD retina is the change of subpopulation abundance, rather than generation of new subcluster. Transcription factor enrichment analysis further highlights the key regulators of metabolic-mitochondrial states of Müller glias in Early AMD patients especially. Our study demonstrates new characteristics of retinal gliosis associated with Early AMD and suggests the possibility to prevent degeneration by intervening mitochondrial functions of Müller cells.
Use of an invertebrate animal model (Aplysia californica) to develop novel neural interfaces for neuromodulation
Authors: Zhuo Junqi , Gill Jeffrey P. , Jansen E. Duco , Jenkins Michael W. , Chiel Hillel J.
Published: December 2022

New tools for monitoring and manipulating neural activity have been developed with steadily improving functionality, specificity, and reliability, which are critical both for mapping neural circuits and treating neurological diseases. This review focuses on the use of an invertebrate animal, the marine mollusk Aplysia californica, in the development of novel neurotechniques. We review the basic physiological properties of Aplysia neurons and discuss the specific aspects that make it advantageous for developing novel neural interfaces: First, Aplysia nerves consist only of unmyelinated axons with various diameters, providing a particularly useful model of the unmyelinated C fibers in vertebrates that are known to carry important sensory information, including those that signal pain. Second, Aplysia’s neural tissues can last for a long period in an ex vivo experimental setup. This allows comprehensive tests such as the exploration of parameter space on the same nerve to avoid variability between animals and minimize animal use. Third, nerves in large Aplysia can be many centimeters in length, making it possible to easily discriminate axons with different diameters based on their conduction velocities. Aplysia nerves are a particularly good approximation of the unmyelinated C fibers, which are hard to stimulate, record, and differentiate from other nerve fibers in vertebrate animal models using epineural electrodes. Fourth, neurons in Aplysia are large, uniquely identifiable, and electrically compact. For decades, researchers have used Aplysia for the development of many novel neurotechnologies. Examples include high-frequency alternating current (HFAC), focused ultrasound (FUS), optical neural stimulation, recording, and inhibition, microelectrode arrays, diamond electrodes, carbon fiber microelectrodes, microscopic magnetic stimulation and magnetic resonance electrical impedance tomography (MREIT). We also review a specific example that illustrates the power of Aplysia for accelerating technology development: selective infrared neural inhibition of small-diameter unmyelinated axons, which may lead to a translationally useful treatment in the future. Generally, Aplysia is suitable for testing modalities whose mechanism involves basic biophysics that is likely to be similar across species. As a tractable experimental system, Aplysia californica can help the rapid development of novel neuromodulation technologies.
Brain areas modulation in consciousness during sevoflurane anesthesia
Authors: Lyu Jie , Cai Huajing , Chen Yeru , Chen Gang
Published: December 2022

Sevoflurane is presently one of the most used inhaled anesthetics worldwide. However, the mechanisms through which sevoflurane acts and the areas of the brain associated with changes in consciousness during anesthesia remain important and complex research questions. Sevoflurane is generally regarded as a volatile anesthetic that blindly targets neuronal (and sometimes astrocyte) GABAA receptors. This review focuses on the brain areas of sevoflurane action and their relation to changes in consciousness during anesthesia. We cover 20 years of history, from the bench to the bedside, and include perspectives on functional magnetic resonance, electroencephalogram, and pharmacological experiments. We review the interactions and neurotransmitters involved in brain circuits during sevoflurane anesthesia, improving the effectiveness and accuracy of sevoflurane’s future application and shedding light on the mechanisms behind human consciousness.
C-low threshold mechanoreceptor activation becomes sufficient to trigger affective pain in spinal cord-injured mice in association with increased respiratory rates
Authors: Noble Donald J. , Dongmo Rochinelle , Parvin Shangrila , Martin Karmarcha K. , Garraway Sandra M.
Published: December 2022

The mechanisms of neuropathic pain after spinal cord injury (SCI) are not fully understood. In addition to the plasticity that occurs within the injured spinal cord, peripheral processes, such as hyperactivity of primary nociceptors, are critical to the expression of pain after SCI. In adult rats, truncal stimulation within the tuning range of C-low threshold mechanoreceptors (C-LTMRs) contributes to pain hypersensitivity and elevates respiratory rates (RRs) after SCI. This suggests that C-LTMRs, which normally encode pleasant, affiliative touch, undergo plasticity to transmit pain sensation following injury. Because tyrosine hydroxylase (TH) expression is a specific marker of C-LTMRs, in the periphery, here we used TH-Cre adult mice to investigate more specifically the involvement of C-LTMRs in at-level pain after thoracic contusion SCI. Using a modified light-dark chamber conditioned place aversion (CPA) paradigm, we assessed chamber preferences and transitions between chambers at baseline, and in response to mechanical and optogenetic stimulation of C-LTMRs. In parallel, at baseline and select post-surgical timepoints, mice underwent non-contact RR recordings and von Frey assessment of mechanical hypersensitivity. The results showed that SCI mice avoided the chamber associated with C-LTMR stimulation, an effect that was more pronounced with optical stimulation. They also displayed elevated RRs at rest and during CPA training sessions. Importantly, these changes were restricted to chronic post-surgery timepoints, when hindpaw mechanical hypersensitivity was also evident. Together, these results suggest that C-LTMR afferent plasticity, coexisting with potentially facilitatory changes in breathing, drives at-level affective pain following SCI in adult mice.
A new iron supplement: The chelate of pig skin collagen peptide and Fe2+ can treat iron-deficiency anemia by modulating intestinal flora
Authors: Jiang Shan , Dong Weichao , Zhang Zhen , Xu Jing , Li Haoran , Zhang Jiayu , Dai Long , Wang Shaoping
Published: December 2022

Introduction

Iron deficiency anemia (IDA) is one of the most common nutritional diseases encountered all over the world. Nowadays, oral iron supplementation is still the mainstay of IDA treatment.

Methods

In this study, a new iron nutritional supplement named pig skin collagen peptides ferrous chelates (PSCP-Fe) was prepared, and its structure was characterized by the scanning electron microscopy, sykam amino acid analyzer and Fourier transform infrared spectroscopy (FTIR). The anti-IDA activity of PSCP-Fe was evaluated in low-Fe2+ diet-induced IDA in rats. 16S amplicon sequencing technology was then used to reveal the mechanism of PSCP-Fe against IDA.

Results

The results of amino acid analysis and FTIR showed that aspartic acid (Asp), arginine (Arg), histidine (His), glutamic acid (Glu), cystine (Cys), and lysine (Lys) residued in PSCP chelated readily with Fe2+ through their functional groups. PSCP-Fe treated reversed the hematology-related indexes, such as red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentrate (MCHC), serum ferritin (SF), serum hepcidin (HEPC) and serum transferrin receptor (TFR). And its regulatory action was better than that of FeSO4. Moreover, PSCP-Fe alleviated the hepatocyte apoptosis and necrosis, Fe2+ loss, and injury in IDA rats. In addition, PSCP-Fe could significantly retrace the disturbed profile of gut microbiota in IDA rats (p < 0.05) and significantly up-regulated the relative abundances of nine bacterial genus, including Lactobacillus, Alloprevotella, unclassified_of_Oscillospiraceae, and NK4A214_group (p < 0.05). It could also downgrade the relative abundances of Subdoligranulum and Coriobacteriaceae_UCG-002 (p < 0.05). The results of Spearman’s correlation analysis and distance-based redundancy analysis (db-RDA) revealed that Subdoligranulum and Christensenellaceae_R-7_group may be potential microbial markers for effective PSCP-Fe action in the treatment of IDA.

Discussion

Overall, our results elucidate the interactions between gut bacteria and related cytokines and reveal the mechanisms underlying the anti-IDA effect of PSCP-Fe. They will thus provide a theoretical foundation for PSCP-Fe as a new iron nutritional supplement.
Anti-diabetic prospects of dietary bio-actives of millets and the significance of the gut microbiota: A case of finger millet
Authors: Singh Vineet , Lee GyuDae , Son HyunWoo , Amani Sliti , Baunthiyal Mamta , Shin Jae-Ho
Published: December 2022

Finger millet (Eleusine coracana) is a staple food in several parts of the world because of its high nutritional value. In addition to its high nutrient content, finger millet contains numerous bioactive compounds, including polyphenol (10.2 mg/g TAE), flavonoid (5.54 mg/g CE), phytic acid (0.48%), and dietary fiber (15–20%). Polyphenols are known for their anti-oxidant and anti-diabetic role. Phytic acid, previously considered an anti-nutritive substance, is now regarded as a nutraceutical as it reduces carbohydrate digestibility and thus controls post-prandial glucose levels and obesity. Thus, finger millet is an attractive diet for patients with diabetes. Recent findings have revealed that the anti-oxidant activity and bio-accessibility of finger millet polyphenols increased significantly (P < 0.05) in the colon, confirming the role of the gut microbiota. The prebiotic content of finger millet was also utilized by the gut microbiota, such as Faecalibacterium, Eubacterium, and Roseburia, to generate colonic short-chain fatty acids (SCFAs), and probiotic Bifidobacterium and Lactobacillus, which are known to be anti-diabetic in nature. Notably, finger millet-induced mucus-degrading Akkermansia muciniphila can also help in alleviate diabetes by releasing propionate and Amuc_1100 protein. Various millet bio-actives effectively controlled pathogenic gut microbiota, such as Shigella and Clostridium histolyticum, to lower gut inflammation and, thus, the risk of diabetes in the host. In the current review, we have meticulously examined the role of gut microbiota in the bio-accessibility of millet compounds and their impact on diabetes.
SlBEL11 affects tomato carotenoid accumulation by regulating SlLCY-b2
Authors: He Yan , Wang Yu , Zhang Mengzhuo , Liu Guangsen , Tian Cong , Xu Xiangbin , Pan Yonggui , Shi Xuequn , Zhang Zhengke , Meng Lanhuan
Published: December 2022

Extensive data have demonstrated that carotenoid accumulation in tomato fruit is influenced by environmental cues and hormonal signals. However, there is insufficient information on the mechanism of its transcriptional regulation, as many molecular roles of carotenoid biosynthetic pathways remain unknown. In this work, we found that the silence of the BEL1-like family transcription factor (TF) BEL1-LIKE HOMEODOMAIN 11 (SlBEL11) enhanced carotenoid accumulation in virus induced gene silencing (VIGS) analysis. In its RNA interference (RNAi) transgenic lines, a significant increase in the transcription level for the lycopene beta cyclase 2 (SlLCY-b2) gene was detected, which encoded a key enzyme located at the downstream branch of the carotenoid biosynthetic pathway. In Electrophoretic mobility shift assay (EMSA), SlBEL11 protein was confirmed to bind to the promoter of SlLCY-b2 gene. In addition, the dual-luciferase reporter assay showed its intrinsic transcriptional repression activity. Collectively, our findings added a new member to the carotenoid transcriptional regulatory network and expanded the functions of the SlBEL11 transcription factor.
Phenolic profile, alpha-amylase inhibitory activity, and in vitro glycemic index of adzuki beans
Authors: Muhammad Mazhar , Zhu Yong , Wen Anyan , Liu Na , Qin Likang
Published: December 2022

Regular consumption of low-glycemic index (GI) foods is a common strategy for type 2 diabetes patients. To evaluate the potential application of adzuki beans in low-GI foods, the phenolic profile and alpha-amylase inhibitor (α-AI) activity of four varieties of adzuki beans (G24, Te Xiao Li No. 1, Gui Nong No. 1, and Qian Xiao Hei) were determined. The starch digestibility properties and in vitro glycemic index (IVGI) of these beans were also evaluated using the in vitro digestion model coupled with 3,5-dinitrosalicylic acid colorimetry. The results indicated that these adzuki beans, containing numerous phenolics, showed inhibitory activities to alpha-amylase with the α-AI activities between 1.760 ± 0.044 and 3.411 ± 0.186 U/g. The resistant starch (RS) contributed predominantly to the total starch with proportions between (69.78 ± 2.45%) and (81.03 ± 0.06%); Te Xiao Li No. 1 was the highest compared with the other varieties. The adzuki beans were categorized into low- or medium-GI foods, and the IVGI ranged from (39.00 ± 0.36) to (56.76 ± 4.21). These results suggested that adzuki beans can be used as a component of low-GI foods.
Environmental cues for healthy food marketing: The importance of in-store research into three conversions
Authors: Larsen Nils Magne , Sigurdsson Valdimar , Gunnarsson Didrik
Published: December 2022

Since retailers control the space where consumers tend to make the vast majority of their food purchase decisions, they can take measures to promote healthy living. Increasing relative sales of healthy food can contribute to the ongoing battle against preventable lifestyle diseases. We show how retailers can use impression management and environmental cues in their stores to influence consumers' sales responses to healthy food. This paper advocates in-store research in this realm and introduces three consumer behavior levels - reaching, stopping/holding, and closing the sale - as micro-conversions when retailers use impression management on their consumers. We showcase impression management at each conversion level by testing the effects of placing healthy and unhealthy food items on a floor display in the store area with the most traffic, with or without background music and an advertisement. The results demonstrate that a healthy food product can outperform the sales of popular unhealthy foods. The floor display, for example, increased the sales of the targeted “healthy product” by 570% on average during the intervention periods, compared with the baseline. We discuss the importance of in-store research into three conversions to enable further development of impression management and the use of environmental cues for healthy food promotion.
Role of tumor-derived exosomes in metastasis, drug resistance and diagnosis of clear cell renal cell carcinoma
Authors: Jiang Tiancheng , Zhu Zepeng , Zhang Jiawei , Chen Ming , Chen Shuqiu
Published: December 2022

Renal cancer is one of the most extensively studied human tumors today, with clear cell renal cell carcinoma accounting for approximately 80% of all cases. Despite recent advances in research on clear cell renal cell carcinoma, advanced distant metastasis of the disease, delay in diagnosis, as well as drug resistance remain major problems. In recent years, as an important mediator of material and information exchange between cells in the tumor microenvironment, exosomes have attracted widespread attention for their role in tumor development. It has been reported that tumor-derived exosomes may act as regulators and have an important effect on the metastasis, drug resistance formation, and providing targets for early diagnosis of clear cell renal cell carcinoma. Therefore, the extensive study of tumour-derived exosomes will provide a meaningful reference for the development of the diagnostic and therapeutic field of clear cell renal cell carcinoma. This article reviews the biological role and research progress of tumor-derived exosomes in different aspects of premetastatic niche formation, tumor angiogenesis, and epithelial-mesenchymal transition during the progression of clear cell renal cell carcinoma. In addition, the role of tumor-derived exosomes in the development of drug resistance in clear cell renal cell carcinoma is also addressed in this review. Furthermore, recent studies have found that cargoes of exosomes in serum and urine, for example, a series of miRNAs, have the potential to be biological markers of clear cell renal cell carcinoma and provide meaningful targets for early diagnosis and monitoring of tumors, which is also covered in this article.
Novel targeted treatments in hairy cell leukemia and other hairy cell-like disorders
Authors: Maitre Elsa , Paillassa Jerome , Troussard Xavier
Published: December 2022

In the category of mature B-cell neoplasms, splenic B-cell lymphoma and leukemia were clearly identified and include four distinct entities: hairy cell leukemia (HCL), splenic marginal zone lymphoma (SMZL), splenic diffuse red pulp lymphoma (SDRPL) and the new entity named splenic B-cell lymphoma/leukemia with prominent nucleoli (SBLPN). The BRAFV600E mutation is detected in nearly all HCL cases and offers a possibility of targeted therapy. BRAF inhibitors (BRAFi) represent effective and promising therapeutic approaches in patients with relapsed/refractory HCL. Vemurafenib and dabrafenib were assessed in clinical trials. The BRAFV600E mutation is missing in SDRPL and SBLPN: mitogen-activated protein kinase 1 (MAP2K1) mutations were found in 40% of SBLPN and VH4-34+ HCL patients, making possible to use MEK inhibitors (MEKi) such as trametinib, cobimetinib or binimetinib in monotherapy or associated with BRAFi. Other mutations may be associated and other signaling pathways involved, including the B-cell receptor signaling (BCR), cell cycle, epigenetic regulation and/or chromatin remodeling. In SDRPL, cyclin D3 (CCND3) mutations were found in 24% of patients, offering the possibility of using cell cycle inhibitors. Even if new emerging drugs, particularly those involved in the epigenetic regulation, have recently been added to the therapeutic armamentarium in HCL and HCL-like disorders, purine nucleoside analogs more and more associated with anti-CD20 monoclonal antibodies, are still used in the frontline setting. Thanks to the recent discoveries in genetics and signaling pathways in HCL and HCL-like disorders, new targeted therapies have been developed, have proven their efficacy and safety in several clinical trials and become essential in real life: BRAFi, MEKi, Bruton Tyrosine Kinase inhibitors (BTKi) and anti-CD22 immunotoxins. New other drugs emerged and have to be assessed in the future. In this article, we will discuss the main mutations identified in HCL and HCL-like disorders and the signaling pathways potentially involved in the pathogenesis of the different hairy cell disorders. We will discuss the results of the recent clinical trials, which will help us to propose an algorithm useful in clinical practice and we will highlight the different new drugs that may be used in the near future.
Role of cuproptosis-related gene in lung adenocarcinoma
Authors: Liu Yuan , Lin Wei , Yang Ying , Shao JingJing , Zhao Hongyu , Wang Gaoren , Shen Aiguo
Published: December 2022

Backgrounds

Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer, which is the leading cause of cancer death. Dysregulation of cell proliferation and death plays a crucial role in the development of LUAD. As of recently, the role of a new form of cell death, cuproptosis, and it has attracted more and more attention. As of yet, it is not clear whether cuproptosis is involved in the progression of LUAD.

Methods

An integrated set of bioinformatics tools was utilized to analyze the expression and prognostic significance of cuproptosis-related genes. Meanwhile, a robust risk signature was developed using machine learning based on prognostic cuproptosis-related genes and explored the value of prognostic cuproptosis-related signature for clinical applications, functional enrichment and immune landscape. Lastly, the dysregulation of the cuproptosis-related genes in LUAD was validated by in vitro experiment.

Results

In this study, first, cuproptosis-related genes were found to be differentially expressed in LUAD patients of public databases, and nine of them had prognostic value. Next, a cuproptosis-related model with five features (DLTA, MTF1, GLS, PDHB and PDHA1) was constructed to separate the patients into high- and low-risk groups based on median risk score. Internal validation set and external validation set were used for model validation and evaluation. What’s more, Enrichment analysis of differential genes and the WGCNA identified that cuproptosis-related signatures affected tumor prognosis by influencing tumor immunity. Small molecule compounds were predicted based on differential expressed genes to improve poor prognosis in the high-risk group and a nomogram was constructed to further advance clinical applications. In closing, our data showed that FDX1 affected the prognosis of lung cancer by altering the expression of cuproptosis-related signature.

Conclusion

A new cuproptosis-related signature for survival prediction was constructed and validated by machine learning algorithm and in vitro experiments to reflect tumor immune infiltration in LUAD patients. The purpose of this article was to provide a potential diagnostic and therapeutic strategy for LUAD.
Gallic acid inhibits neuroinflammation and reduces neonatal hypoxic-ischemic brain damages
Authors: Dong Xiangjun , Luo Shuyue , Hu Dongjie , Cao Ruixue , Wang Qunxian , Meng Zijun , Feng Zijuan , Zhou Weihui , Song Weihong
Published: December 2022

Neuroinflammation is a leading cause of secondary neuronal injury in neonatal hypoxic-ischemic encephalopathy (HIE). Regulation of neuroinflammation may be beneficial for treatment of HIE and its secondary complications. Gallic acid (GA) has been shown to have anti-inflammatory and antioxidant effects. In this report we found that oxygen-glucose deprivation and/reoxygenation (OGD/R)-induced cell death, and the generation of excessive reactive oxygen species (ROS) and inflammatory cytokines by microglia were inhibited by GA treatment. Furthermore, GA treatment reduced neuroinflammation and neuronal loss, and alleviated motor and cognitive impairments in rats with hypoxic-ischemic brain damage (HIBD). Together, our results reveal that GA is an effective regulator of neuroinflammation and has potential as a pharmaceutical intervention for HIE therapy.
Ursolic acid and rosmarinic acid ameliorate alterations in hippocampal neurogenesis and social memory induced by amyloid beta in mouse model of Alzheimer’s disease
Authors: Mirza Fatima Javed , Zahid Saadia
Published: December 2022

Alzheimer’s disease (AD) is a multifaceted neurodegenerative disorder characterized by substantial neuronal damage which manifests in the form of deficits in memory and cognition. In spite of the debilitating nature of Alzheimer’s disease (AD), a dearth of treatment strategies calls for the need to develop therapeutic agents that stimulate neurogenesis and alleviate the associated cognitive deficits. The present study investigates the therapeutic potential of two major phytochemicals, rosmarinic acid (RA) and ursolic acid (UA) in an amyloid beta1–42 (Aβ1–42)-induced model of AD. UA, a natural pentacyclic triterpenoid and RA, a phenolic ester are major bioactive constituents of Rosmarinus officinalis, which is a medicinal herb belonging to family Lamiaceae and exhibiting significant biological properties including neuroprotection. Donepezil, a second generation cholinesterase inhibitor approved for the treatment of mild, moderate and severe Alzheimer’s disease (AD) is used as control. Out of eight groups of male BALB/c mice, stereotaxic surgery was performed on four groups (n = 6 each) to introduce Aβ1–42 in the hippocampus followed by treatment with vehicle (phosphate-buffered saline (PBS)), donepezil, UA or RA. The other four groups were given vehicle, donepezil, UA and RA only. Behavior analysis for social interaction was performed which constitutes the social affiliation and the social novelty preference test. Presence of Aβ plaques and expression of neurogenesis markers i.e., doublecortin (DCX) and Ki-67 were also assessed. Results revealed the neuroprotective effect of UA and RA observed through substantial reduction in Aβ plaques as compared to the Aβ1-42- and donepezil-treated groups. The neuronal density was also restored as evident via DCX and Ki-67 immunoreactivity in Aβ1–42 + RA and Aβ1–42+UA-treated groups in comparison to Aβ1–42-treated and Aβ1–42+donepezil-treated groups. The social affiliation was reestablished in the Aβ1–42 administered groups treated with UA and RA. Molecular docking studies further validated the comparable binding of UA and RA with Ki-67 and DCX to that of donepezil. Our findings suggest that UA and RA are potential neuroprotective compounds that reverses the histological hallmarks of AD and ameliorate impaired social memory and hippocampal neurogenesis.
A review of recent advances on single use of antibody-drug conjugates or combination with tumor immunology therapy for gynecologic cancer
Authors: Wang An-Jin , Gao Yang , Shi Yu-Ying , Dai Meng-Yuan , Cai Hong-Bing
Published: December 2022

Immune checkpoint inhibitors have made significant progress in the treatment of various cancers. However, due to the low ICI responsive rate for the gynecologic cancer, ICI two-drug combination therapy tends to be a predominant way for clinical treatment. Antibody-drug conjugates, a promising therapeutic modality for cancer, have been approved by the FDA for breast cancer, lymphoma, multiple myeloma and gastric cancer. On September 2021, the FDA granted accelerated approval to tisotumab vedotin for patients with recurrent or metastatic cervical cancer. Currently, the role of therapy of ADCs on gynecologic tumors was also included in medication regimens. Now more than 30 ADCs targeting for 20 biomarkers are under clinical trials in the field, including monotherapy or combination with others for multiple lines of therapy. Some ADCs have been proved to enhance the antitumor immunity effect on both pre-clinical models and clinical trials. Therefore, combination of ADCs and ICIs are expected in clinical trials. In this review, we discuss current development of ADCs in gynecologic oncology and the combination effects of ICIs and ADCs.
Early mechanisms of neutrophil activation and transmigration in acute lung injury
Authors: Cagle L. A. , Linderholm A. L. , Franzi L. M. , Last J. A. , Simon S. I. , Kenyon N. J. , Harper R. W.
Published: December 2022

Introduction:Neutrophil transmigration is multifactorial and primarily driven by selectins and β2-integrins (CD11b/CD18), whose expression are dependent on the underlying stimulus. Ventilator-induced lung injury (VILI) results in a predominantly CD18-independent mechanism of neutrophil recruitment, while direct endotoxin-induced lung injury results from a CD18-dependent mechanism. We previously observed that lack of NADPH oxidases DUOX1 and DUOX2 resulted in reduced neutrophil influx in a VILI model of lung injury but had no influence on neutrophil influx after LPS exposure. Based on these observations, we hypothesized that DUOX1/DUOX2 are an important component of CD18-independent mechanisms of neutrophil recruitment in the lung.

Methods:We exposedDuoxa−/−(KO) mice andDuoxa+/+(WT) mice to either an intratracheal exposure of lipopolysaccharide (LPS/endotoxin)-or high tidal volume ventilation and compared expression of neutrophil markers between groups. WT mice (129S6/SvEvTac) were obtained from Taconic Biosciences (One Discovery Drive Suite 304; Rensselaer, NY 1244) and were allowed to acclimatize for one week prior to study enrollment. KO mice were generated as previously described [Grasberger 2012] and bred in-house on a 129S6 background. We provided positive-pressure ventilation at a tidal volume of 10 ml/kg with 2 cmH20 positive end-expiratory pressure (PEEP). Mice were assigned to groups consisting of KO (n = 5) and WT (n = 5) in each group and divided into non-ventilated, positive-pressure ventilation, or LPS IT exposure groups. Positive-pressure ventilation was instituted for 4-h using a FlexiVent (Flexiware 8.1, Scireq, Montreal, QC, Canada). Lipopolysaccharide (Salmonella enterica serotype tryphimurium L6143, Millipore Sigma) was administered via an intratracheal (IT) route at a dose of 0.1 mg/kg. Mice were humanely euthanized at 4-h post-injection consistent with the UC Davis IAUCAC-approved protocol.

Results:As previously observed, neutrophilic influx into the airways was significantly impaired in theDuoxa−/−(KO) mice after VILI, but not after LPS exposure. LPS-induced lung injury resulted in upregulation of CD11b+neutrophils and shedding of CD62L and CD162 regardless of DUOX expression, whereas VILI resulted in upregulation of CD49+neutrophils in theDuoxa+/+(WT) mice but not theDuoxa−/−(KO) mice.

Conclusion:Our data suggest DUOX is required for CD18-independent mechanisms of neutrophil recruitment in the lung induced by acute lung injury, but not for canonical CD18depedent mechanisms after LPS exposure.
Extracellular vesicle characteristics and microRNA content in cerebral palsy and typically developed individuals at rest and in response to aerobic exercise
Authors: Vechetti Ivan J. , Norrbom Jessica , Alkner Björn , Hjalmarsson Emma , Palmcrantz Alexandra , Pontén Eva , Pingel Jessica , von Walden Ferdinand , Fernandez-Gonzalo Rodrigo
Published: December 2022

In this study, the properties of circulating extracellular vesicles (EVs) were examined in cerebral palsy (CP) and typically developed (TD) individuals at rest and after aerobic exercise, focusing on the size, concentration, and microRNA cargo of EVs. Nine adult individuals with CP performed a single exercise bout consisting of 45 min of Frame Running, and TD participants completed either 45 min of cycling (n = 10; TD EX) or were enrolled as controls with no exercise (n = 10; TD CON). Blood was drawn before and 30 min after exercise and analyzed for EV concentration, size, and microRNA content. The size of EVs was similar in CP vs. TD, and exercise had no effect. Individuals with CP had an overall lower concentration (∼25%, p < 0.05) of EVs. At baseline, let-7a, let-7b and let-7e were downregulated in individuals with CP compared to TD (p < 0.05), while miR-100 expression was higher, and miR-877 and miR-4433 lower in CP compared to TD after exercise (p < 0.05). Interestingly, miR-486 was upregulated ∼2-fold in the EVs of CP vs. TD both at baseline and after exercise. We then performed an in silico analysis of miR-486 targets and identified the satellite cell stemness factor Pax7 as a target of miR-486. C2C12 myoblasts were cultured with a miR-486 mimetic and RNA-sequencing was performed. Gene enrichment analysis revealed that several genes involved in sarcomerogenesis and extracellular matrix (ECM) were downregulated. Our data suggest that circulating miR-486 transported by EVs is elevated in individuals with CP and that miR-486 alters the transcriptome of myoblasts affecting both ECM- and sarcomerogenesis-related genes, providing a link to the skeletal muscle alterations observed in individuals with CP.
Inflammation and oxidative stress in salt sensitive hypertension; The role of the NLRP3 inflammasome
Authors: Ertuglu Lale A. , Mutchler Ashley Pitzer , Yu Justin , Kirabo Annet
Published: December 2022

Salt-sensitivity of blood pressure is an independent risk factor for cardiovascular disease and affects approximately half of the hypertensive population. While the precise mechanisms of salt-sensitivity remain unclear, recent findings on body sodium homeostasis and salt-induced immune cell activation provide new insights into the relationship between high salt intake, inflammation, and hypertension. The immune system, specifically antigen-presenting cells (APCs) and T cells, are directly implicated in salt-induced renal and vascular injury and hypertension. Emerging evidence suggests that oxidative stress and activation of the NLRP3 inflammasome drive high sodium-mediated activation of APCs and T cells and contribute to the development of renal and vascular inflammation and hypertension. In this review, we summarize the recent insights into our understanding of the mechanisms of salt-sensitive hypertension and discuss the role of inflammasome activation as a potential therapeutic target.
Diminished schwann cell repair responses play a role in delayed diabetes-associated wound healing
Authors: Zhou Shaolong , Wan Lingling , Liu Xu , Hu Delin , Lu Feng , Chen Xihang , Liang Fangguo
Published: December 2022

Diabetes mellitus is the most common metabolic disease associated with impaired wound healing. Recently, Schwann cells (SCs), the glia of the peripheral nervous system, have been suggested to accelerate normal skin wound healing. However, the roles of SCs in diabetic wound healing are not fully understood. In this study, Full-thickness wounds were made in the dorsal skin of C57/B6 mice and db/db (diabetic) mice. Tissue samples were collected at different time points, and immunohistochemical and immunofluorescence analyses were performed to detect markers of de-differentiated SCs, including myelin basic protein, Sox 10, p75, c-Jun, and Ki67. In addition, in vitro experiments were performed using rat SC (RSC96) and murine fibroblast (L929) cell lines to examine the effects of high glucose conditions (50 mM) on the de-differentiation of SCs and the paracrine effects of SCs on myofibroblast formation. Here, we found that, compared with that in normal mice, wound healing was delayed and SCs failed to rapidly activate a repair program after skin wound injury in diabetic mice. Furthermore, we found that SCs from diabetic mice displayed functional impairments in cell de-differentiation, cell-cycle re-entry, and cell migration. In vitro, hyperglycemia impaired RSC 96 cell de-differentiation, cell-cycle re-entry, and cell migration, as well as their paracrine effects on myofibroblast formation, including the secretion of TGF-β and Timp1. These results suggest that delayed wound healing in diabetes is due in part to a diminished SC repair response and attenuated paracrine effects on myofibroblast formation.
Farming system effects on root rot pathogen complex and yield of faba bean (vicia faba) in Germany
Authors: Šišić Adnan , Baćanović-Šišić Jelena , Schmidt Harald , Finckh Maria R.
Published: December 2022

A survey across Germany was undertaken from 2016-2019 to evaluate effects of management system (organic vs conventional), pedo-climatic conditions and crop rotation history on faba bean root health status, diversity of major root rot pathogens and yield. Root rot incidence was generally low and there was no effect of the management system on the spectrum of pathogens isolated. Among the most common fungal species identified, frequencies ofFusarium redolensandDidymella pinodellawere significantly higher in roots from organic fields compared with conventional and lower was observed forF. avenaceum,F. tricinctumandF. culmorum. Faba bean roots were colonized at similar rates byF. equisetiand the members of theF. oxysporum(FOSC) andF. solani(FSSC) species complexes in both management systems. Almost no legumes had been grown in the 5-11 years preceding the conventional faba beans surveyed while legumes had almost always been present during this period in the organic fields. This difference in rotational histories between the farming systems led to apparent cropping systems effects on the isolation frequencies of several species. For example,D. pinodellawas ubiquitous in organic fields with a high frequency of legumes in the rotations but much rarer and often absent in conventional fields. Pedo-climatic conditions, particularly cool conditions at sowing and plant emergence and/or during the vegetative season favored most of the most prevalentFusariumspecies identified in this study. In organic systems, yields correlated negatively withD. pinodellaandF. redolensfrequencies whereas higher levels ofF. tricintumin faba bean roots had a positive correlation with yield. In conventional systems, faba bean yields depended more on the total precipitation before sowing and during the main growing season but were also negatively correlated with the frequencies of FOSC andF. culmorum. Phylogenetic analysis based on theTEF1 alphalocus indicated that the FSSC isolates mainly belonged to theF. pisilineage. In contrast, the FOSC isolates were placed in 9 different lineages, with a conspicuous dominance ofF. libertatisthat has until now not been associated with any leguminous host.
Evolutionary reconstruction, nomenclature and functional meta-analysis of the Kiwellin protein family
Authors: Klemm Paul , Christ Marvin , Altegoer Florian , Freitag Johannes , Bange Gert , Lechner Marcus
Published: December 2022

Crop diseases caused by pathogens critically affect global food security and plant ecology. Pathogens are well adapted to their host plants and have developed sophisticated mechanisms allowing successful colonization. Plants in turn have taken measures to counteract pathogen attacks resulting in an evolutionary arms race. Recent studies provided mechanistic insights into how two plant Kiwellin proteins from Zea mays mitigate the activity of the chorismate mutase Cmu1, a virulence factor secreted by the fungal pathogen Ustilago maydis during maize infection. Formerly identified as human allergens in kiwifruit, the biological function of Kiwellins is apparently linked to plant defense. We combined the analysis of proteome data with structural predictions to obtain a holistic overview of the Kiwellin protein family, that is subdivided into proteins with and without a N-terminal kissper domain. We found that Kiwellins are evolutionarily conserved in various plant species. At median five Kiwellin paralogs are encoded in each plant genome. Structural predictions revealed that Barwin-like proteins and Kiwellins cannot be discriminated purely at the sequence level. Our data shows that Kiwellins emerged in land plants (embryophyta) and are not present in fungi as suggested earlier. They evolved via three major duplication events that lead to clearly distinguishable subfamilies. We introduce a systematic Kiwellin nomenclature based on a detailed evolutionary reconstruction of this protein family. A meta-analysis of publicly available transcriptome data demonstrated that Kiwellins can be differentially regulated upon the interaction of plants with pathogens but also with symbionts. Furthermore, significant differences in Kiwellin expression levels dependent on tissues and cultivars were observed. In summary, our study sheds light on the evolution and regulation of a large protein family and provides a framework for a more detailed understanding of the molecular functions of Kiwellins.
Regulatory mechanism of a heat-activated retrotransposon by DDR complex in Arabidopsis thaliana
Authors: Niu Xiaoying , Chen Lu , Kato Atsushi , Ito Hidetaka
Published: December 2022

The RNA-directed DNA methylation (RdDM) pathway plays an essential role in the transposon silencing mechanism; the DDR complex, consisting of DRD1, DMS3, and RDM1, is an essential component of the RdDM pathway. ONSEN, identified in Arabidopsis, is a retrotransposon activated by heat stress at 37°C; however, studies on the regulation of ONSEN are limited. In this study, we analyzed the regulation of ONSEN activity by the DDR complex in Arabidopsis. We elucidated that loss of any component of the DDR complex increased ONSEN transcript levels. Transgenerational transposition of ONSEN was observed in the DDR-complex mutants treated with heat stress for 48 h. Furthermore, the DDR complex components DRD1, DMS3, and RDM1 played independent roles in suppressing ONSEN transcription and transposition. Moreover, we found that the duration of heat stress affects ONSEN activity. Therefore, the results of this study provide new insights into the retrotransposon regulatory mechanisms of the DDR complex in the RdDM pathway.