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Intracellular protein aggregation causes proteotoxic stress, underlying highly debilitating neurodegenerative disorders in parallel with decreased proteasome activity. Nevertheless, under such stress conditions, the expression of proteasome subunits is upregulated by Nuclear Factor Erythroid 2-related factor 1 (NRF1), a transcription factor that is encoded by NFE2L1. Activating the NRF1 pathway could accordingly delay the onset of neurodegenerative and other disorders with impaired cell proteostasis. Here, we present a series of small-molecule compounds based on bis(phenylmethylen)cycloalkanones and their heterocyclic analogues, identified via targeted library screening, that can induce NRF1-dependent downstream events, such as proteasome synthesis, heat shock response, and autophagy, in both model cell lines and Caenorhabditis elegans strains. These compounds increase proteasome activity and decrease the size and number of protein aggregates without causing any cellular stress or inhibiting the ubiquitin-proteasome system (UPS). Therefore, our compounds represent a new promising therapeutic approach for various protein conformational diseases, including the most debilitating neurodegenerative diseases., Competing Interests: Declaration of Competing Interest J.S., Z.S., M.A., L.S., P.M., A.M. and K.G.S. have filed several patent applications regarding this work. The authors declare the following financial interests, which may be considered as potential competing interests: Klara Grantz Saskova has a financial interest in Adalid Sciences. She is co-founder and CEO of Adalid Sciences. Michael Adamek is an employee of Adalid Sciences. If there are other authors, they declare that they have no known competing financial interests that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: Inflammation contributes to morbidity following subarachnoid hemorrhage (SAH). The authors of this study evaluate how applying noninvasive transauricular vagus nerve stimulation (taVNS) can target this deleterious inflammatory response following SAH and reduce the rate of radiographic vasospasm., Methods: In this prospective, triple-blinded, randomized controlled trial, 27 patients were randomized to taVNS or sham stimulation. Serial blood and CSF samples were collected every 3 days to quantify inflammatory markers. Radiographic cerebral vasospasm severity and functional outcomes (modified Rankin Scale scores) were analyzed., Results: No adverse events occurred. Radiographic vasospasm was significantly reduced (p = 0.018), with serial vessel caliber measurements demonstrating a more rapid return to normal than in the sham-treated group (p < 0.001). In the taVNS group, tumor necrosis factor-α was significantly reduced in both plasma (days 7 and 10) and CSF (day 13); interleukin-6 was also significantly reduced in plasma (day 4) and CSF (day 13) (p < 0.05). Patients receiving taVNS had higher rates of favorable outcomes at discharge (38.4% vs 21.4%) and first follow-up (76.9% vs 57.1%). Patients treated with taVNS had significant improvement in modified Rankin Scale scores from admission to first follow-up (p = 0.014), unlike patients in the sham-treated group (p = 0.18). The taVNS group had a significantly lower rate of discharge to a skilled nursing facility or hospice (p = 0.04)., Conclusions: taVNS is a noninvasive method of neuro- and systemic immunomodulation. This trial supports the finding that taVNS following SAH can mitigate the inflammatory response, reduce radiographic vasospasm, and potentially improve functional and neurological outcomes.

Background/Objectives : Various conditions contribute to the development of postoperative pulmonary complications (PPCs) following thoracic surgery. In this study, the aim was to investigate whether preoperative diaphragm dysfunction is associated with an increased risk of PPCs after lung cancer resection. Methods : We prospectively examined 45 patients scheduled for video-assisted thoracoscopic surgery (VATS) lobectomy or open thoracotomy. Relevant clinical data were retrieved from hospital database records, while diaphragm muscles were assessed using ultrasound. Results : Our results demonstrated that preoperative diaphragm muscle atrophy was significantly associated with a higher risk of developing PPCs compared to patients with normal diaphragm thickness. Diaphragm atrophy was also linked to prolonged hospital stays. Additionally, we observed a moderate correlation between expiratory diaphragm thickness and the number of PPCs. Conclusions : Low diaphragm expiratory thickness is associated with postoperative pulmonary complications after lobectomy for lung cancer. Importantly, unlike other predictive factors such as age, COPD, or smoking, diaphragmatic atrophy is a modifiable risk factor that can potentially be addressed through early therapeutic intervention.

Piscine orthoreovirus-1 and 3 (PRV-1, PRV-3) cause highly prevalent infection in cultured salmonids and can induce heart and skeletal muscle inflammation (HSMI) resulting in economic losses in aquaculture. However, to date, PRV-1 and PRV-3 have withstood replication in continuous cell lines. In this study, we used beating heart cell cultures obtained from different developmental stages of rainbow trout (Oncorhynchus mykiss) (RTC-L and RTC-A) and tested their ability to sustain replication of PRV-1 and PRV-3. Furthermore, we compared the replication pattern of the different viruses with those in the newly developed heart fibroblast cell line (RTH-F) and the traditional established rainbow trout gonad cell line (RTG-2). Neither RTCs nor RTH-F cell lines supported replication of PRV-1 and PRV-3. Comparative experiments showed varying susceptibility of the novel cultures to viral haemorrhagic septicaemia virus (VHSV), chum salmon reovirus (CSV), infectious pancreatic necrosis virus (IPNV), piscine myocarditis virus (PMCV), salmonid alphavirus 3 (SAV-3) and tilapia lake virus (TiLV), indicating their usability for work with multiple fish viruses. While confirming the difficulty of replicating PRV-1 and PRV-3, the results demonstrate the potential of novel heart-derived cell cultures as in vitro tools for studying fish viruses., (© 2025 The Author(s). Journal of Fish Diseases published by John Wiley & Sons Ltd.)

Background: Subarachnoid hemorrhage (SAH) is characterized by intense central inflammation, leading to substantial post-hemorrhagic complications such as vasospasm and delayed cerebral ischemia. Given the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation (taVNS) and its ability to promote brain plasticity, taVNS has emerged as a promising therapeutic option for SAH patients. However, the effects of taVNS on cardiovascular dynamics in critically ill patients, like those with SAH, have not yet been investigated. Given the association between cardiac complications and elevated risk of poor clinical outcomes after SAH, it is essential to characterize the cardiovascular effects of taVNS to ensure this approach is safe in this fragile population. Therefore, this study assessed the impact of both acute and repetitive taVNS on cardiovascular function., Methods: In this randomized clinical trial, 24 SAH patients were assigned to either a taVNS treatment or a sham treatment group. During their stay in the intensive care unit, we monitored patient electrocardiogram readings and vital signs. We compared long-term changes in heart rate, heart rate variability (HRV), QT interval, and blood pressure between the two groups. Additionally, we assessed the effects of acute taVNS by comparing cardiovascular metrics before, during, and after the intervention. We also explored acute cardiovascular biomarkers in patients exhibiting clinical improvement., Results: We found that repetitive taVNS did not significantly alter heart rate, QT interval, blood pressure, or intracranial pressure (ICP). However, repetitive taVNS increased overall HRV and parasympathetic activity compared to the sham treatment. The increase in parasympathetic activity was most pronounced from 2 to 4 days after initial treatment (Cohen's d = 0.50). Acutely, taVNS increased heart rate, blood pressure, and peripheral perfusion index without affecting the corrected QT interval, ICP, or HRV. The acute post-treatment elevation in heart rate was more pronounced in patients who experienced a decrease of more than one point in their modified Rankin Score at the time of discharge., Conclusions: Our study found that taVNS treatment did not induce adverse cardiovascular effects, such as bradycardia or QT prolongation, supporting its development as a safe immunomodulatory treatment approach for SAH patients. The observed acute increase in heart rate after taVNS treatment may serve as a biomarker for SAH patients who could derive greater benefit from this treatment., Funding: The American Association of Neurological Surgeons (ALH), The Aneurysm and AVM Foundation (ALH), The National Institutes of Health R01-EB026439, P41-EB018783, U24-NS109103, R21-NS128307 (ECL, PB), McDonnell Center for Systems Neuroscience (ECL, PB), and Fondazione Neurone (PB)., Clinical Trial Number: NCT04557618., Competing Interests: GT, KD, PD, XL, ZL, MA, KL, AV, TK, JO, GZ, PB No competing interests declared, AH Has stock ownership in Aurenar, EL Has stock ownership in Neurolutions, Face to Face Biometrics, Caeli Vascular, Acera, Sora Neuroscience, Inner Cosmos, Kinetrix, NeuroDev, Inflexion Vascular, Aurenar, Cordance Medical, Silent Surgical, and Petal Surgical; consultant for E15, Neurolutions, Inc, Petal Surgical; Washington University owns equity in Neurolutions, (© 2024, Tan, Huguenard et al.)

Environmental stressors such as micro- and nanosized plastic particles (MNPs) or crude oil have a detrimental effect on aquatic animals; however, the impact upon the cardiovascular system of fish remains relatively under-researched. This study presents a novel approach for investigating the effect of crude oil and MNPs on the cardiac system of fish. We used salmonid larvae and cardiac cell cultures derived from hearts of salmonid fish and exposed them to environmental stressors. Following exposure to plastic particles or crude oil, the larvae exhibited some variation in contraction rate. In contrast, significant alterations in the contraction rate were observed in all cardiac cell cultures. The greatest differences between the control and treatment groups were observed in cardiac cell cultures derived from older brown trout. Following 7 days of exposure to MNPs or crude oil in Atlantic salmon larval hearts or cardiac cell cultures, there were only minor responses noted in mRNA expression of the selected marker genes. These findings show the use of a novel in vitro technique contributing to the existing body of knowledge on the impact of MNPs and crude oil on the cardiovascular system of salmonids and the associated risk., (© 2024 The Author(s). Journal of Fish Diseases published by John Wiley & Sons Ltd.)

Tilapia Lake Virus (TiLV) is associated with pathological changes in the brain of infected fish, but the mechanisms driving the virus's neuropathogenesis remain poorly characterized. TiLV establishes a persistent infection in the brain of infected fish even when the virus is no longer detectable in the peripheral organs, rendering therapeutic interventions and disease management challenging. Moreover, the persistence of the virus in the brain may pose a risk for viral reinfection and spread and contribute to ongoing tissue damage and neuroinflammatory processes. In this review, we explore TiLV-associated neurological disease. We discuss the possible mechanism(s) used by TiLV to enter the central nervous system (CNS) and examine TiLV-induced neuroinflammation and brain immune responses. Lastly, we discuss future research questions and knowledge gaps to be addressed to significantly advance this field.

The realm of natural product (NP) research is constantly expanding, with diverse applications in both medicine and industry. In this interdisciplinary field, scientists collaborate to investigate various aspects of NPs, including understanding the mode of action of these compounds, unraveling their biosynthetic pathways, studying evolutionary aspects, and biochemically characterizing the enzymes involved. However, this collaboration can be challenging as all parties involved come from very different backgrounds (such as microbiology, synthetic chemistry, biochemistry, or bioinformatics) and may not use the same terminology. Fortunately, contemporary technologies, such as videos, provide novel avenues for effective engagement. Recognizing the potency of visual stimuli in explaining complex processes, we envision a future where animations become more and more common in interdisciplinary communication, accompanying perspectives, and reviews. To demonstrate how such approaches can enhance the understanding of complex processes, we have animated the biosynthesis of the glycopeptide antibiotic vancomycin (https://youtu.be/TGAgC4c8hvo)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Crawling robots are becoming increasingly prevalent in both industrial and private applications. Despite their many advantages over other robot types, they have complex movement mechanics. Artificial intelligence can simplify this by reinforcement learning. This process requires configuring the training environment and defining input parameters, including a robot model for movement training. To translate the virtual results into real-world scenarios, a 3D model with appropriate mechanical parameters must be developed.These parameters can vary significantly between multiple mechanical configurations, which will further impact the reinforcement learning process of such a robot. For this reason, it was decided to test which limb configurations would work best in this process. Initially, various kinematic types of walking robots were analysed, drawing on the anatomy of mammals, reptiles, and insects for the biological model. The reptilian model was chosen for its balance of stability, dynamics, and energy efficiency. The article reviews the preparation of robot models and the configuration of the Unity3D development environment using the ML-Agents toolkit. The experiment examined how different limb lengths affect training, resulting in movement algorithms for various quadruped robot configurations using artificial neural networks. Based on the numerical results, the best configuration was the default, with the same length of the tibia as the thigh, achieving a reward function value of 883.9 and an episode length of 245.5. Taking into account the same criteria, the least efficient configuration was definitely the one characterised by the shortest thigh and the longest tibia among those considered. In its case, the reward function reached a value of only 526.2 with an episode lasting 999.0, which means that it never achieved the intended goal., Competing Interests: Declarations Competing interest The authors do not have any conflict of interest to declare. Data availability The data that support the findings of this study are available from the corresponding author upon reasonable request. Code availability The code that supports the findings of this study is available from the corresponding author upon request., (© 2024. The Author(s).)

This paper explores an application of 3D printing technology on the food industry. Since its inception in the 1980s, 3D printing has experienced a huge rise in popularity. This study uses cost-effective, flexible, and sustainable components that enable specific features of certain gas chromatography. This study aims to optimize the process of gas detection using a 3D printed separation column and the MiCS-6814 sensor. The principle of the entire device is based on the idea of utilizing a simple capillary chromatographic column manufactured by 3D printing for the separation of samples into components prior to their measurement using inexpensive chemiresistive sensors. An optimization of a system with a 3D printed PLA block containing a capillary, a mixing chamber, and a measuring chamber with a MiCS-6814 sensor was performed. The optimization distributed the sensor output signal in the time domain so that it was possible to distinguish the peak for the two most common alcohols, ethanol and methanol. The paper further describes some optimization types and their possibilities.

Despite long knowing what brain areas support language comprehension, our knowledge of the neural computations that these frontal and temporal regions implement remains limited. One important unresolved question concerns functional differences among the neural populations that comprise the language network. Here we leveraged the high spatiotemporal resolution of human intracranial recordings (n = 22) to examine responses to sentences and linguistically degraded conditions. We discovered three response profiles that differ in their temporal dynamics. These profiles appear to reflect different temporal receptive windows, with average windows of about 1, 4 and 6 words, respectively. Neural populations exhibiting these profiles are interleaved across the language network, which suggests that all language regions have direct access to distinct, multiscale representations of linguistic input-a property that may be critical for the efficiency and robustness of language processing., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Subarachnoid hemorrhage (SAH) is characterized by intense central inflammation, leading to substantial post-hemorrhagic complications such as vasospasm and delayed cerebral ischemia. Given the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation (taVNS) and its ability to promote brain plasticity, taVNS has emerged as a promising therapeutic option for SAH patients. However, the effects of taVNS on cardiovascular dynamics in critically ill patients, like those with SAH, have not yet been investigated. Given the association between cardiac complications and elevated risk of poor clinical outcomes after SAH, it is essential to characterize the cardiovascular effects of taVNS to ensure this approach is safe in this fragile population. Therefore, we assessed the impact of both acute taVNS and repetitive taVNS on cardiovascular function in this study., Methods: In this randomized clinical trial, 24 SAH patients were assigned to either a taVNS treatment or a Sham treatment group. During their stay in the intensive care unit, we monitored patient electrocardiogram (ECG) readings and vital signs. We compared long-term changes in heart rate, heart rate variability, QT interval, and blood pressure between the two groups. Additionally, we assessed the effects of acute taVNS by comparing cardiovascular metrics before, during, and after the intervention. We also explored acute cardiovascular biomarkers in patients exhibiting clinical improvement., Results: We found that repetitive taVNS did not significantly alter heart rate, QT interval, blood pressure, or intracranial pressure. However, taVNS increased overall heart rate variability and parasympathetic activity compared to the sham treatment. The increase in parasympathetic activity was most pronounced from 2-4 days after initial treatment (Cohen's d = 0.50). Acutely, taVNS increased heart rate, blood pressure, and peripheral perfusion index without affecting the corrected QT interval, intracranial pressure, or heart rate variability. The acute post-treatment elevation in heart rate was more pronounced in patients who experienced a decrease of more than one point in their Modified Rankin Score at the time of discharge., Conclusions: Our study found that taVNS treatment did not induce adverse cardiovascular effects, such as bradycardia or QT prolongation, supporting its development as a safe immunomodulatory treatment approach for SAH patients. The observed acute increase in heart rate after taVNS treatment may serve as a biomarker for SAH patients who could derive greater benefit from this treatment., Trial Registration: NCT04557618., Competing Interests: Declaration of competing interest Eric Leuthardt has stock ownership in Neurolutions, Face to Face Biometrics, Caeli Vascular, Acera, Sora Neuroscience, Inner Cosmos, Kinetrix, NeuroDev, Inflexion Vascular, Aurenar, Cordance Medical, Silent Surgical, and Petal Surgical. He is a consultant for E15, Neurolutions, Inc., Petal Surgical. Washington University owns equity in Neurolutions. Anna Huguenard has stock ownership in Aurenar.

Determining the presence and frequency of neural oscillations is essential to understanding dynamic brain function. Traditional methods that detect peaks over 1/ f noise within the power spectrum fail to distinguish between the fundamental frequency and harmonics of often highly non-sinusoidal neural oscillations. To overcome this limitation, we define fundamental criteria that characterize neural oscillations and introduce the cyclic homogeneous oscillation (CHO) detection method. We implemented these criteria based on an autocorrelation approach to determine an oscillation's fundamental frequency. We evaluated CHO by verifying its performance on simulated non-sinusoidal oscillatory bursts and validated its ability to determine the fundamental frequency of neural oscillations in electrocorticographic (ECoG), electroencephalographic (EEG), and stereoelectroencephalographic (SEEG) signals recorded from 27 human subjects. Our results demonstrate that CHO outperforms conventional techniques in accurately detecting oscillations. In summary, CHO demonstrates high precision and specificity in detecting neural oscillations in time and frequency domains. The method's specificity enables the detailed study of non-sinusoidal characteristics of oscillations, such as the degree of asymmetry and waveform of an oscillation. Furthermore, CHO can be applied to identify how neural oscillations govern interactions throughout the brain and to determine oscillatory biomarkers that index abnormal brain function., Competing Interests: HC One U.S. patent (Provisional Application Serial No.63/326,257) related to systems and methodsfor detection of neurophysiological signal oscillations described in this manuscript was filed on March 31, 2022. The inventors/contributors of this patent involve some of themanuscript authors, including HC, MA, JTW, PB, MA, JW No competing interests declared, PB One U.S. patent (Provisional Application Serial No.63/326,257) related to systems and methods

DDI2 is an aspartic protease that cleaves polyubiquitinated substrates. Upon proteotoxic stress, DDI2 activates the transcription factor TCF11/NRF1 (NFE2L1), crucial for maintaining proteostasis in mammalian cells, enabling the expression of rescue factors, including proteasome subunits. Here, we describe the consequences of DDI2 ablation in vivo and in cells. DDI2 knock-out (KO) in mice caused embryonic lethality at E12.5 with severe developmental failure. Molecular characterization of embryos showed insufficient proteasome expression with proteotoxic stress, accumulation of high molecular weight ubiquitin conjugates and induction of the unfolded protein response (UPR) and cell death pathways. In DDI2 surrogate KO cells, proteotoxic stress activated the integrated stress response (ISR) and induced a type I interferon (IFN) signature and IFN-induced proliferative signaling, possibly ensuring survival. These results indicate an important role for DDI2 in the cell-tissue proteostasis network and in maintaining a balanced immune response., Competing Interests: The authors declare that they have no conflict of interest., (© 2024 The Author(s).)

Fatigue and dyspnea are the most commonly reported long-term complaints in individuals previously infected with SARS-CoV-2. This study aimed to comprehensively evaluate diaphragm muscle function in post-COVID-19 patients and investigate whether potential diaphragm dysfunction contributes to physical functioning impairment. A total of 46 patients who qualified for pulmonary rehabilitation were examined. Diaphragm muscle function parameters were evaluated using ultrasonography, while the severity of dyspnea, aerobic capacity, and the amount of energy used by the body during physical activity were assessed using the six-minute walk test, mMRC scale, and Metabolic Equivalent Task (MET), respectively. We identified that 69.5% of patients had diaphragm atrophy and 6.5% had diaphragm paralysis. The percentage of atrophy was not related to age, gender, BMI, oxygen therapy usage during the COVID-19 infection course, and disease severity. Patients who experienced cough, fever, and no loss of smell during the COVID-19 course had significantly greater diaphragm inspiratory thickness values, while patients with cough and no smell disorders had a significantly lower percentage of diaphragm atrophy. Diaphragm functional parameters were strongly associated with selected variables of exercise tolerance, such as distance in the six-minute walk test, oxygen saturation levels, fatigue, and exertion on the Borg scale. In conclusion, diaphragm muscle dysfunction is a serious long-term post-COVID-19 consequence and can be viewed as a major contributing factor to prolonged functional impairments.

The purpose of this study was to conduct a systematic review and meta-analysis of case reports presenting HCC spread to the diaphragm muscle and to determine possible risk factors for this condition. An extensive literature search was performed using the following electronic databases: MEDLINE, CINAHL, ScienceDirect, Google Scholar, and DOAJ. A total of 18 articles describing 27 hepatocellular carcinoma patients were included in this review. The presence of HCC cells in the superior liver segment is strongly associated with metastases to the diaphragm. Among the two types of diaphragm involvement by HCC cells, diaphragm infiltration occurs much more frequently than diaphragm adhesion. However, an HCC nodule in the 8th liver segment and a higher number of liver segments involved by HCC cells predispose patients to diaphragm adhesion. Hepatitis B is a risk factor for diaphragm metastases in recurrent HCC. The tumor diameter is not associated with HCC spread to the diaphragm muscle. We did not find specific symptoms reported by patients that could indicate HCC metastasis to the diaphragm muscle. The presence of hepatitis B and the localization of HCC cells in superior liver segments, especially in the 8th liver segment, should be take into consideration in the diagnostic process.

Background: Inflammation has been implicated in driving the morbidity associated with subarachnoid hemorrhage (SAH). Despite understanding the important role of inflammation in morbidity following SAH, there is no current effective way to modulate this deleterious response. There is a critical need for a novel approach to immunomodulation that can be safely, rapidly, and effectively deployed in SAH patients. Vagus nerve stimulation (VNS) provides a non-pharmacologic approach to immunomodulation, with prior studies demonstrating VNS can reduce systemic inflammatory markers, and VNS has had early success treating inflammatory conditions such as arthritis, sepsis, and inflammatory bowel diseases. The aim of the Non-invasive Auricular Vagus nerve stimulation for Subarachnoid Hemorrhage (NAVSaH) trial is to translate the use of non-invasive transcutaneous auricular VNS (taVNS) to spontaneous SAH, with our central hypothesis being that implementing taVNS in the acute period following spontaneous SAH attenuates the expected inflammatory response to hemorrhage and curtails morbidity associated with inflammatory-mediated clinical endpoints., Materials and Methods: The overall objectives for the NAHSaH trial are to 1) Define the impact that taVNS has on SAH-induced inflammatory markers in the plasma and cerebrospinal fluid (CSF), 2) Determine whether taVNS following SAH reduces radiographic vasospasm, and 3) Determine whether taVNS following SAH reduces chronic hydrocephalus. Following presentation to a single enrollment site, enrolled SAH patients are randomly assigned twice daily treatment with either taVNS or sham stimulation for the duration of their intensive care unit stay. Blood and CSF are drawn before initiation of treatment sessions, and then every three days during a patient's hospital stay. Primary endpoints include change in the inflammatory cytokine TNF-α in plasma and cerebrospinal fluid between day 1 and day 13, rate of radiographic vasospasm, and rate of requirement for long-term CSF diversion via a ventricular shunt. Secondary outcomes include exploratory analyses of a panel of additional cytokines, number and type of hospitalized acquired infections, duration of external ventricular drain in days, interventions required for vasospasm, continuous physiology data before, during, and after treatment sessions, hospital length of stay, intensive care unit length of stay, and modified Rankin Scale score (mRS) at admission, discharge, and each at follow-up appointment for up to two years following SAH., Discussion: Inflammation plays a central role in morbidity following SAH. This NAVSaH trial is innovative because it diverges from the pharmacologic status quo by harnessing a novel non-invasive neuromodulatory approach and its known anti-inflammatory effects to alter the pathophysiology of SAH. The investigation of a new, effective, and rapidly deployable intervention in SAH offers a new route to improve outcomes following SAH., Trial Registration: Clinical Trials Registered, NCT04557618. Registered on September 21, 2020, and the first patient was enrolled on January 4, 2021., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: ALH and ECL hold equity in the company Aurenar, LLC. The COI as it relates to this trial has been managed by Washington University., (Copyright: © 2024 Huguenard et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This paper presents computer and color vision research focusing on human color perception in VR environments. A VR art gallery with digital twins of original artworks is created for this experiment. In this research, the field of colorimetry and the application of the L*a*b* and RGB color models are applied. The inter-relationships of the two color models are applied to create a color modification of the VR art gallery environment using C# Script procedures. This color-edited VR environment works with a smooth change in color tone in a given time interval. At the same time, a sudden change in the color of the RGB environment is defined in this interval. This experiment aims to record a user's reaction embedded in a VR environment and the effect of color changes on human perception in a VR environment. This research uses lie detector sensors that record the physiological changes of the user embedded in VR. Five sensors are used to record the signal. An experiment on the influence of the user's color perception in a VR environment using lie detector sensors has never been conducted. This research defines the basic methodology for analyzing and evaluating the recorded signals from the lie detector. The presented text thus provides a basis for further research in the field of colors and human color vision in a VR environment and lays an objective basis for use in many scientific and commercial areas.

Inexpensive chemiresistive sensors are often insufficiently selective as they are sensitive to multiple components of the gas mixture at the same time. One solution would be to insert a device in front of the sensor that separates the measured gas mixture and possibly isolates the unwanted components. This study focused on the fabrication and characterization of a compact unit, which was fabricated by 3D printing, for the separation and detection of simple gas mixtures. The capillary, the basic part of the compact unit, was 4.689 m long and had a diameter of 0.7 mm. The compact unit also contained a mixing chamber on the inlet side and a measuring chamber with a MiCS-6814 sensor on the outlet side. Mixtures of ethanol and water at different concentrations were chosen for characterization. The measured calibration curve was found to have a reliability of R 2 = 0.9941. The study further addressed the elements of environmental friendliness of the materials used and their sustainability.

Due to their capacity to mediate repetitive protein interactions, intrinsically disordered regions (IDRs) are crucial for the formation of various types of protein-RNA complexes. The functions of IDRs are strongly modulated by post-translational modifications (PTMs). Phosphorylation is the most common and well-studied modification of IDRs, which can alter homomeric or heteromeric interactions of proteins and impact their ability to phase separate. Moreover, phosphorylation can influence the RNA-binding properties of proteins, and recent studies demonstrated its selective impact on the global profiles of protein-RNA binding and regulation. These findings highlight the need for further integrative approaches to understand how signalling remodels protein-RNA networks in cells., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

HnRNP A/B belongs to the heterogeneous nuclear ribonucleoprotein (hnRNP) family and plays an important role in regulating viral protein translation and genome replication. Here, we found that overexpression of hnRNP A/B promoted spring viremia of carp virus (SVCV) and cyprinid herpesvirus 3 (CyHV3) replication. Further, hnRNP A/B was shown to act as a negative regulator of type I interferon (IFN) response. Mechanistically, hnRNP A/B interacted with MITA, TBK1 and IRF3 to initiate their degradation. In addition, hnRNP A/B bound to the kinase domain of TBK1, the C terminal domain of MITA and IAD domain of IRF3, and the RRM1 domain of hnRNP A/B bound to TBK1, RRM2 domain bound to IRF3 and MITA. Our study provides novel insights into the functions of hnRNP A/B in regulating host antiviral response., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Decision-makers objectively commit to a definitive choice, yet at the subjective level, human decisions appear to be associated with a degree of uncertainty. Whether decisions are definitive (i.e., concluding in all-or-none choices), or whether the underlying representations are graded, remains unclear. To answer this question, we recorded intracranial neural signals directly from the brain while human subjects made perceptual decisions. The recordings revealed that broadband gamma activity reflecting each individual's decision-making process, ramped up gradually while being graded by the accumulated decision evidence. Crucially, this grading effect persisted throughout the decision process without ever reaching a definite bound at the time of choice. This effect was most prominent in the parietal cortex, a brain region traditionally implicated in decision-making. These results provide neural evidence for a graded decision process in humans and an analog framework for flexible choice behavior., (© 2024. The Author(s).)

Background: Inflammation contributes to morbidity following subarachnoid hemorrhage (SAH). Transauricular vagus nerve stimulation (taVNS) offers a noninvasive approach to target the inflammatory response following SAH., Methods: In this prospective, triple-blinded, randomized, controlled trial, twenty-seven patients were randomized to taVNS or sham stimulation. Blood and cerebrospinal fluid (CSF) were collected to quantify inflammatory markers. Cerebral vasospasm severity and functional outcomes (modified Rankin Scale, mRS) were analyzed., Results: No adverse events occurred. Radiographic vasospasm was significantly reduced (p = 0.018), with serial vessel caliber measurements demonstrating a more rapid return to normal than sham (p < 0.001). In the taVNS group, TNF-α was significantly reduced in both plasma (days 7 and 10) and CSF (day 13); IL-6 was also significantly reduced in plasma (day 4) and CSF (day 13) (p < 0.05). Patients receiving taVNS had higher rates of favorable outcomes at discharge (38.4% vs 21.4%) and first follow-up (76.9% vs 57.1%), with significant improvement from admission to first follow-up (p = 0.014), unlike the sham group (p = 0.18). The taVNS group had a significantly lower rate of discharge to skilled nursing facility or hospice (p = 0.04)., Conclusion: taVNS is a non-invasive method of neuro- and systemic immunomodulation. This trial supports that taVNS following SAH can mitigate the inflammatory response, reduce radiographic vasospasm, and potentially improve functional and neurological outcomes. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04557618.

Although a growing body of evidence emphasizes the superiority of VATS over conventional thoracotomy, little is still known about early postoperative diaphragm muscle function after lobectomy via these two approaches. To fill the gap in existing literature, we conducted a comparative study between VATS and conventional thoracotomy in terms of postoperative diaphragm muscle function, assessing its contractility, strength, the magnitude of effort and potential risk of dysfunction such as atrophy and paralysis. A total of 59 patients (30 after VATS), who underwent anatomical pulmonary resection at our institution, were enrolled in this study. The control group consisted of 28 health subjects without medical conditions that could contribute to diaphragm dysfunction. Diaphragm muscle was assessed before and after surgery using ultrasonography. We found that both surgical approaches were associated with postoperative impairment of diaphragm muscle function-compared to baseline data. Postoperative reduction in diaphragm contraction was demonstrated in most of the 59 patients. In the case of the control group, the differences between measurements were not observed. We noted that lobectomy via thoracotomy was linked with a greater percentage of patients with diaphragm paralysis and/or atrophy than VATS. Similar findings were observed in referring to diaphragm magnitude effort, as well as diaphragm contraction strength, where minimally invasive surgery was associated with better diaphragm function parameters-in comparison to thoracotomy. Disturbance of diaphragm work was reported both at the operated and non-operated side. Upper-right and left lobectomy were connected with greater diaphragm function impairment than other segments. In conclusion, the VATS technique seems to be less invasive than conventional thoracotomy providing a better postoperative function of the main respiratory muscle.

The AID/APOBECs are a group of zinc-dependent cytidine deaminases that catalyse the deamination of bases in nucleic acids, resulting in a cytidine to uridine transition. Secreted novel AID/APOBEC-like deaminases (SNADs), characterized by the presence of a signal peptide are unique among all of intracellular classical AID/APOBECs, which are the central part of antibody diversity and antiviral defense. To date, there is no available knowledge on SNADs including protein characterization, biochemical characteristics and catalytic activity. We used various in silico approaches to define the phylogeny of SNADs, their common structural features, and their potential structural variations in fish species. Our analysis provides strong evidence of the universal presence of SNAD1 proteins/transcripts in fish, in which expression commences after hatching and is highest in anatomical organs linked to the immune system. Moreover, we searched published fish data and identified previously, "uncharacterized proteins" and transcripts as SNAD1 sequences. Our review into immunological research suggests SNAD1 role in immune response to infection or immunization, and interactions with the intestinal microbiota. We also noted SNAD1 association with temperature acclimation, environmental pollution and sex-based expression differences, with females showing higher level. To validate in silico predictions we performed expression studies of several SNAD1 gene variants in carp, which revealed distinct patterns of responses under different conditions. Dual sensitivity to environmental and pathogenic stress highlights its importance in the fish and potentially enhancing thermotolerance and immune defense. Revealing the biological roles of SNADs represents an exciting new area of research related to the role of DNA and/or RNA editing in fish biology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Majewska, Dietrich, Budzko, Adamek, Figlerowicz and Ciereszko.)

Detecting temporal and spectral features of neural oscillations is essential to understanding dynamic brain function. Traditionally, the presence and frequency of neural oscillations are determined by identifying peaks over 1/f noise within the power spectrum. However, this approach solely operates within the frequency domain and thus cannot adequately distinguish between the fundamental frequency of a non-sinusoidal oscillation and its harmonics. Non-sinusoidal signals generate harmonics, significantly increasing the false-positive detection rate - a confounding factor in the analysis of neural oscillations. To overcome these limitations, we define the fundamental criteria that characterize a neural oscillation and introduce the Cyclic Homogeneous Oscillation (CHO) detection method that implements these criteria based on an auto-correlation approach that determines the oscillation's periodicity and fundamental frequency. We evaluated CHO by verifying its performance on simulated sinusoidal and non-sinusoidal oscillatory bursts convolved with 1/f noise. Our results demonstrate that CHO outperforms conventional techniques in accurately detecting oscillations. Specifically, we determined the sensitivity and specificity of CHO as a function of signal-to-noise ratio (SNR). We further assessed CHO by testing it on electrocorticographic (ECoG, 8 subjects) and electroencephalographic (EEG, 7 subjects) signals recorded during the pre-stimulus period of an auditory reaction time task and on electrocorticographic signals (6 SEEG subjects and 6 ECoG subjects) collected during resting state. In the reaction time task, the CHO method detected auditory alpha and pre-motor beta oscillations in ECoG signals and occipital alpha and pre-motor beta oscillations in EEG signals. Moreover, CHO determined the fundamental frequency of hippocampal oscillations in the human hippocampus during the resting state (6 SEEG subjects). In summary, CHO demonstrates high precision and specificity in detecting neural oscillations in time and frequency domains. The method's specificity enables the detailed study of non-sinusoidal characteristics of oscillations, such as the degree of asymmetry and waveform of an oscillation. Furthermore, CHO can be applied to identify how neural oscillations govern interactions throughout the brain and to determine oscillatory biomarkers that index abnormal brain function., Competing Interests: Competing Interests One U.S. patent (Provisional Application Serial No.63/326,257) related to systems and methods for detection of neurophysiological signal oscillations described in this manuscript was filed on March 31, 2022. The inventors/contributors of this patent involve some of the manuscript authors, including HC, MA, JTW, PB.

Introduction: Carp edema virus (CEV) is a fish poxvirus that primarily infects the gills of common carp. CEV causes koi sleepy disease (KSD), which is highly contagious and can result in mortality of up to 100%., Methods: In the present study, we analyzed the stress and immune responses during KSD in two strains of common carp with different resistance to CEV: susceptible koi and resistant Amur sazan. Experiments were performed at two temperatures: 12°C and 18°C. In the case of koi carp, we also analyzed the effect of supplementation of 0.6% NaCl into tank water, which prevents mortality of the CEV-infected fish (salt rescue model)., Results: We found that CEV-infected koi kept at 18°C had the highest viral load, which correlated with the most severe histopathological changes in the gills. CEV infection resulted in the activation of stress response reflected by the upregulated expression of genes involved in stress response in the stress axis organs and increased levels of cortisol and glucose in the blood plasma. These changes were the most pronounced in CEV-infected koi kept at 18°C. At both temperatures, the activation of antiviral immune response was observed in koi kept under freshwater and NaCl conditions upon CEV infection. Interestingly, a clear downregulation of the expression of adaptive immune genes was observed in CEV-infected koi kept under freshwater at 18°C., Conclusion: CEV induces a stress response and modulates adaptive immune response in koi, and this is correlated with the level of viral load and disease development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Zawisza, Rebl, Teitge, Krzystyniak, Piackova, Gela, Kocour, Chadzinska, Adamek and Rakus.)

Background: Inflammation has been implicated in driving the morbidity associated with subarachnoid hemorrhage (SAH). Despite understanding the important role of inflammation in morbidity following SAH, there is no current effective way to modulate this deleterious response. There is a critical need for a novel approach to immunomodulation that can be safely, rapidly, and effectively deployed in SAH patients. Vagus nerve stimulation (VNS) provides a non-pharmacologic approach to immunomodulation, with prior studies demonstrating VNS can reduce systemic inflammatory markers, and VNS has had early success treating inflammatory conditions such as arthritis, sepsis, and inflammatory bowel diseases. The aim of the Non-invasive Auricular Vagus nerve stimulation for Subarachnoid Hemorrhage (NAVSaH) trial is to translate the use of non-invasive transcutaneous auricular VNS (taVNS) to spontaneous SAH, with our central hypothesis being that implementing taVNS in the acute period following spontaneous SAH attenuates the expected inflammatory response to hemorrhage and curtails morbidity associated with inflammatory-mediated clinical endpoints., Materials and Methods: The overall objectives for the NAHSaH trial are to 1) Define the impact that taVNS has on SAH-induced inflammatory markers in the plasma and cerebrospinal fluid (CSF), 2) Determine whether taVNS following SAH reduces radiographic vasospasm, and 3) Determine whether taVNS following SAH reduces chronic hydrocephalus. Following presentation to a single enrollment site, enrolled SAH patients are randomly assigned twice daily treatment with either taVNS or sham stimulation for the duration of their intensive care unit stay. Blood and CSF are drawn before initiation of treatment sessions, and then every three days during a patient's hospital stay. Primary endpoints include change in the inflammatory cytokine TNF-α in plasma and cerebrospinal fluid between day 1 and day 13, rate of radiographic vasospasm, and rate of requirement for long-term CSF diversion via a ventricular shunt. Secondary outcomes include exploratory analyses of a panel of additional cytokines, number and type of hospitalized acquired infections, duration of external ventricular drain in days, interventions required for vasospasm, continuous physiology data before, during, and after treatment sessions, hospital length of stay, intensive care unit length of stay, and modified Rankin Scale score (mRS) at admission, discharge, and each at follow-up appointment for up to two years following SAH., Discussion: Inflammation plays a central role in morbidity following SAH. This NAVSaH trial is innovative because it diverges from the pharmacologic status quo by harnessing a novel non-invasive neuromodulatory approach and its known anti-inflammatory effects to alter the pathophysiology of SAH. The investigation of a new, effective, and rapidly deployable intervention in SAH offers a new route to improve outcomes following SAH., Trial Registration: Clinical Trials Registered, NCT04557618. Registered on September 21, 2020, and the first patient was enrolled on January 4, 2021., Competing Interests: Competing interests ALH and ECL hold equity in the company Aurenar, LLC. ECL also has stock ownership in Neurolutions, Face to Face Biometrics, Caeli Vascular, Acera, Sora Neuroscience, Inner Cosmos, Kinetrix, NeuroDev, Inflexion Vascular, Cordance Medical, Silent Surgical, and Petal Surgical. He is a consultant for E15, Neurolutions, Inc., Petal Surgical. Washington University owns equity in Neurolutions. The COI as it relates to this trial has been managed by Washington University.

Guided by the reasoned action approach, this study examined select individual, information, and social factors that influence intention toward pursuing a career in geriatrics among 314 clinical medical and nursing students in Ghana. A Poisson regression showed attitude toward older persons was a significant influencing factor of intention to choose a career in geriatrics for medical students (B = 0.015, SE = 0.0048, p = 0.002) but not nursing students (B = 0.009, SE = 0.0145, p = 0.512). Personal interest was, however, a significant influencing factor for both medical and nursing students (B = 0.462, SE = 0.0592, p = 0.000) and (B = 0.015, SE = 0.0048, p = 0.002), respectively. Nursing students with moderate to strong interest were 1.6 times more likely to express an intention to specialize in geriatrics, and medical students were 1.5 times more likely to express an intention to specialize in geriatrics. The results show that the most important factor influencing geriatric career intention is students' personal interest in the field. Evidence-based interventions such as early educational and practice exposure to the field and interactions with older adults are recommended., (© 2024 John Wiley & Sons Australia, Ltd.)

Limitations in chronic pain therapies necessitate novel interventions that are effective, accessible, and safe. Brain-computer interfaces (BCIs) provide a promising modality for targeting neuropathology underlying chronic pain by converting recorded neural activity into perceivable outputs. Recent evidence suggests that increased frontal theta power (4-7 Hz) reflects pain relief from chronic and acute pain. Further studies have suggested that vibrotactile stimulation decreases pain intensity in experimental and clinical models. This longitudinal, non-randomized, open-label pilot study's objective was to reinforce frontal theta activity in six patients with chronic upper extremity pain using a novel vibrotactile neurofeedback BCI system. Patients increased their BCI performance, reflecting thought-driven control of neurofeedback, and showed a significant decrease in pain severity (1.29 ± 0.25 MAD, p = 0.03, q = 0.05) and pain interference (1.79 ± 1.10 MAD p = 0.03, q = 0.05) scores without any adverse events. Pain relief significantly correlated with frontal theta modulation. These findings highlight the potential of BCI-mediated cortico-sensory coupling of frontal theta with vibrotactile stimulation for alleviating chronic pain., (© 2024. The Author(s).)

Phenols, and especially their nitrated analogues, are ubiquitous pollutants and known carcinogens which have already been linked to forest decline. Although nitrophenols have been widely recognized as harmful to different aquatic and terrestrial organisms, we could not find any literature assessing their toxicity to terrestrial plants. Maize (monocot) and sunflower (dicot) were exposed to phenolic pollutants, guaiacol (GUA) and 4-nitroguaiacol (4NG), through a hydroponics system under controlled conditions in a growth chamber. Their acute physiological response was studied during a two-week root exposure to different concentrations of xenobiotics (0.1, 1.0, and 10 mM). The exposure visibly affected plant growth and the effect increased with increasing xenobiotic concentration. In general, 4NG affected plants more than GUA. Moreover, sunflower exhibited an adaptive response, especially to low and moderate GUA concentrations. The integrity of both plant species deteriorated during the exposure: biomass and photochemical pigment content were significantly reduced, which reflected in the poorer photochemical efficiency of photosystem II. Our results imply that 4NG is taken up by sunflower plants, where it could enter a lignin biosynthesis pathway., (© 2024. The Author(s).)

This study focuses on an applicability of the device designed for monitoring dough fermentation. The device combines a complex system of thermodynamic sensors (TDSs) with an electronic nose (E-nose). The device's behavior was tested in experiments with dough samples. The configuration of the sensors in the thermodynamic system was explored and their response to various positions of the heat source was investigated. When the distance of the heat source and its intensity from two thermodynamic sensors changes, the output signal of the thermodynamic system changes as well. Thus, as the distance of the heat source decreases or the intensity increases, there is a higher change in the output signal of the system. The linear trend of this change reaches an R 2 value of 0.936. Characteristics of the doughs prepared from traditional and non-traditional flours were successfully detected using the electronic nose. To validate findings, the results of the measurements were compared with signals from the rheofermentometer Rheo F4, and the correlation between the output signals was closely monitored. The data after statistical evaluation show that the measurements using thermodynamic sensors and electronic nose directly correlate the most with the measured values of the fermenting dough volume. Pearson's correlation coefficient for TDSs and rheofermentometer reaches up to 0.932. The E-nose signals also correlate well with dough volume development, up to 0.973. The data and their analysis provided by this study declare that the used system configuration and methods are fully usable for this type of food analysis and also could be usable in other types of food based on the controlled fermentation. The system configuration, based on the result, will be also used in future studies.

Objective. Single-pulse electrical stimulation (SPES) has been widely used to probe effective connectivity. However, analysis of the neural response is often confounded by stimulation artifacts. We developed a novel matching pursuit-based artifact reconstruction and removal method (MPARRM) capable of removing artifacts from stimulation-artifact-affected electrophysiological signals. Approach. To validate MPARRM across a wide range of potential stimulation artifact types, we performed a bench-top experiment in which we suspended electrodes in a saline solution to generate 110 types of real-world stimulation artifacts. We then added the generated stimulation artifacts to ground truth signals (stereoelectroencephalography signals from nine human subjects recorded during a receptive speech task), applied MPARRM to the combined signal, and compared the resultant denoised signal with the ground truth signal. We further applied MPARRM to artifact-affected neural signals recorded from the hippocampus while performing SPES on the ipsilateral basolateral amygdala in nine human subjects. Main results. MPARRM could remove stimulation artifacts without introducing spectral leakage or temporal spread. It accommodated variable stimulation parameters and recovered the early response to SPES within a wide range of frequency bands. Specifically, in the early response period (5-10 ms following stimulation onset), we found that the broadband gamma power (70-170 Hz) of the denoised signal was highly correlated with the ground truth signal (R=0.98±0.02, Pearson), and the broadband gamma activity of the denoised signal faithfully revealed the responses to the auditory stimuli within the ground truth signal with94%±1.47%sensitivity and99%±1.01%specificity. We further found that MPARRM could reveal the expected temporal progression of broadband gamma activity along the anterior-posterior axis of the hippocampus in response to the ipsilateral amygdala stimulation. Significance. MPARRM could faithfully remove SPES artifacts without confounding the electrophysiological signal components, especially during the early-response period. This method can facilitate the understanding of the neural response mechanisms of SPES., (Creative Commons Attribution license.)

The main object of this research was to develop a security system to evaluate the intrusion into an object through a glass pane. More specifically, this study deals with sensing and evaluating signals from a contact glass-break detector, which is part of an intruder alarm system. Each alarm detector in an alarm system must accomplish certain security level requirements that strictly describe the requirements for the area of use and the detector's reliability. To date, no contact glass-break detector has been developed and fully tested to meet the stringent requirements of the highest security level. A contact glass-break detector was developed whose main part is an accelerometer that transmits signals from the glass pane. These signals were evaluated according to the developed methodology. It was verified that the proposed system can distinguish at the highest security level between false alarms and situations where the building has been intruded.

Anchoringsingle-molecule magnets (SMMs) on the surface of nanostructures is gaining particular interest in the field of molecular magnetism. The accurate organization of SMMs on low-dimensional substrates enables controlled interactions and the possibility of individual molecules' manipulation, paving the route for a broad range of nanotechnological applications. In this comprehensive review article, the most studied types of SMMs are presented, and the quantum-mechanical origin of their magnetic behavior is described. The nanostructured matrices were grouped and characterized to outline to the reader their relevance for subsequent compounding with SMMs. Particular attention was paid to the fact that this process must be carried out in such a way as to preserve the initial functionality and properties of the molecules. Therefore, the work also includes a discussion of issues concerning both the methods of synthesis of the systems in question as well as advanced measurement techniques of the resulting complexes. A great deal of attention was also focused on the issue of surface-molecule interaction, which can affect the magnetic properties of SMMs, causing molecular crystal field distortion or magnetic anisotropy modification, which affects quantum tunneling or magnetic hysteresis, respectively. In our opinion, the analysis of the literature carried out in this way will greatly help the reader to design SMM-nanostructure systems.

Antibiotics are central to modern medicine, and yet they are mainly the products of intra and inter-kingdom evolutionary warfare. To understand how nature evolves antibiotics around a common mechanism of action, we investigated the origins of an extremely valuable class of compounds, lipid II targeting glycopeptide antibiotics (GPAs, exemplified by teicoplanin and vancomycin), which are used as last resort for the treatment of antibiotic resistant bacterial infections. Using a molecule-centred approach and computational techniques, we first predicted the nonribosomal peptide synthetase assembly line of paleomycin, the ancestral parent of lipid II targeting GPAs. Subsequently, we employed synthetic biology techniques to produce the predicted peptide and validated its antibiotic activity. We revealed the structure of paleomycin, which enabled us to address how nature morphs a peptide antibiotic scaffold through evolution. In doing so, we obtained temporal snapshots of key selection domains in nonribosomal peptide synthesis during the biosynthetic journey from ancestral, teicoplanin-like GPAs to modern GPAs such as vancomycin. Our study demonstrates the synergy of computational techniques and synthetic biology approaches enabling us to journey back in time, trace the temporal evolution of antibiotics, and revive these ancestral molecules. It also reveals the optimisation strategies nature has applied to evolve modern GPAs, laying the foundation for future efforts to engineer this important class of antimicrobial agents., (© 2023. The Author(s).)

Replacing fishmeal, a finite resource with high market demand, in the diet of carnivorous rainbow trout with proteins from alternative sources may be a challenge for these fish. Therefore, this study investigated whether replacing fishmeal with protein derived from Hermetia illucens or Arthrospira platensis could promote disease susceptibility in local trout populations with different growth performance. This was assessed in vitro by measuring susceptibility to infection with the viral haemorrhagic septicaemia virus (VHSV) or the bacterium Yersinia ruckeri. Analysis of fin tissue explants and primary cell cultures from scales from the three trout populations infected in vitro with VHSV and gill explants infected with Y. ruckeri showed no significant differences in virus replication or bacterial counts. Evaluation of the virucidal or bactericidal effect of skin mucus showed a significant reduction in viral load and bacterial count for all samples with mucus addition, but no significant difference was observed between the experimental groups. This study documents no apparent impairment of innate immune mechanisms in the skin and gills of trout after feeding a diet replacing fishmeal with Arthrospira or Hermetia proteins. This underlines the potential of these alternative protein sources for the further development of sustainable trout aquaculture., (© 2023 The Authors. Journal of Fish Diseases published by John Wiley & Sons Ltd.)

Sleep-disordered breathing (SDB), i.e., central sleep apnea (CSA) and obstructive sleep apnea (OSA), affects the prognosis of patients with heart failure with reduced ejection fraction (HFrEF). The study assessed the relationships between heart chamber size or function and respiratory parameters in patients with HFrEF and various types of SDB. The 84 participants were patients aged 68.3 ± 8.4 years (80% men) with an average left ventricular ejection fraction (LVEF) of 25.5 ± 6.85% who qualified for cardioverter-defibrillator implantation with or without cardiac resynchronization therapy. SDB, defined by an apnea-hypopnea index (AHI) ≥ five events/hour, was diagnosed in 76 patients (90.5%); SDB was severe in 31 (36.9%), moderate in 26 (31.0%), and mild in 19 (22.6%). CSA was the most common type of SDB (64 patients, 76.2%). A direct proportional relationship existed only in the CSA group between LVEF or stroke volume (SV) and AHI ( p = 0.02 and p = 0.07), and between LVEF or SV and the percentage of total sleep time spent with hemoglobin oxygen saturation < 90% ( p = 0.06 and p = 0.07). In contrast, the OSA group was the only group in which right ventricle size showed a positive relationship with AHI (for basal linear dimension [RVD1] p = 0.06), mean duration of the respiratory event (for RVD1 p = 0.03, for proximal outflow diameter [RVOT proximal] p = 0.009), and maximum duration of respiratory event (for RVD1 p = 0.049, for RVOT proximal p = 0.006). We concluded that in HFrEF patients, SDB severity is related to LV systolic function and SV only in CSA, whereas RV size correlates primarily with apnea/hypopnea episode duration in OSA.

Listeriosis is one of the most serious foodborne diseases caused by the intracellular bacterium Listeria monocytogenes. Its two major virulence factors, broad-range phospholipase C (LmPC-PLC) and the pore-forming toxin listeriolysin O (LLO), enable the bacterium to spread in the host by destroying cell membranes. Here, we determine the crystal structure of LmPC-PLC and complement it with the functional analysis of this enzyme. This reveals that LmPC-PLC has evolved several structural features to regulate its activity, including the invariant position of the N-terminal tryptophan (W1), the structurally plastic active site, Zn 2+ -dependent activity, and the tendency to form oligomers with impaired enzymatic activity. We demonstrate that the enzymatic activity of LmPC-PLC can be specifically inhibited by its propeptide added in trans. Furthermore, we show that the phospholipase activity of LmPC-PLC facilitates the pore-forming activity of LLO and affects the morphology of LLO oligomerization on lipid membranes, revealing the multifaceted synergy of the two virulence factors., (© 2023. Springer Nature Limited.)

Synthetic opals, a composition of homogeneous silica spheres in the mesoscale size range, have attracted the attention of scientists due to their favorable chemical and physical properties. Their chemical inertness and stability, biocompatibility, homogeneity, elevated specific surface area, and ease of functionalization of their surfaces make them a versatile nanotool. In the present study, the Stöber process was used to investigate the effect of parameters, such as reagent concentration and synthesis temperature, on the resulting silica particle size and structure. The optimal conditions for successfully obtaining homogeneous particles in the mesoscale range with high reproducibility were investigated. Several synthesis procedures and their dependence on the reaction temperature were presented to allow the selection of the assumed diameter of silica spheres. The numerous samples obtained were examined for size, homogeneity, structure, and specific surface area. On the basis of specific surface area measurements and nuclear magnetic resonance studies, the internal hierarchical structure of the spherical silica was confirmed as consisting of a solid core and layers of secondary spheres covered by a solid shell. Structural studies (X-ray Spectroscopy, X-ray Absorption Near-Edge Structure, and nuclear magnetic resonance), together with infrared vibrational spectroscopy, showed no dependence of the structure of the obtained mesospheres on the concentration of reagents and the size of the obtained particles.

Electrical activity at high gamma frequencies (70-170 Hz) is thought to reflect the activity of small cortical ensembles. For example, high gamma activity (often quantified by spectral power) can increase in sensory-motor cortex in response to sensory stimuli or movement. On the other hand, synchrony of neural activity between cortical areas (often quantified by coherence) has been hypothesized as an important mechanism for inter-areal communication, thereby serving functional roles in cognition and behavior. Currently, high gamma activity has primarily been studied as a local amplitude phenomenon. We investigated the synchronization of high gamma activity within sensory-motor cortex and the extent to which underlying high gamma activity can explain coherence during motor tasks. We characterized high gamma coherence in sensory-motor networks and the relationship between coherence and power by analyzing electrocorticography (ECoG) data from human subjects as they performed a motor response to sensory cues. We found greatly increased high gamma coherence during the motor response compared with the sensory cue. High gamma power poorly predicted high gamma coherence, but the two shared a similar time course. However, high gamma coherence persisted longer than high gamma power. The results of this study suggest that high gamma coherence is a physiologically distinct phenomenon during a sensory-motor task, the emergence of which may require active task participation. NEW & NOTEWORTHY Motor action after auditory stimulus elicits high gamma responses in sensory-motor and auditory cortex, respectively. We show that high gamma coherence reliably and greatly increased during motor response, but not after auditory stimulus. Underlying high gamma power could not explain high gamma coherence. Our results indicate that high gamma coherence is a physiologically distinct sensory-motor phenomenon that may serve as an indicator of increased synaptic communication on short timescales (∼1 s).

The circadian clock mechanism, which is evolutionarily conserved across various organisms, plays a crucial role in synchronizing physiological responses to external conditions, primarily in response to light availability. By maintaining homeostasis of biological processes and behavior, the circadian clock serves as a key regulator. This biological mechanism also coordinates diurnal oscillations of the immune response during infections. However there is limited information available regarding the influence of circadian oscillation on immune regulation, especially in lower vertebrates like teleost fish. Therefore, the present study aimed to investigate the effects of light and the timing of infection induction on the antiviral immune response in zebrafish. To explore the relationship between the timing of infection and the response activated by viral pathogens, we used a zebrafish model infected with tilapia lake virus (TiLV). Our findings demonstrated that light availability significantly affects the antiviral immune response and the functioning of the molecular clock mechanism during TiLV infection. This is evident through alterations in the expression of major core clock genes and the regulation of TiLV replication and type I IFN pathway genes in the kidney of fish maintained under LD (light-dark) conditions compared to constant darkness (DD) conditions. Moreover, infection induced during the light phase of the LD cycle, in contrast to nocturnal infection, also exhibited similar effects on the expression of genes associated with the antiviral response. This study indicates a more effective mechanism of the zebrafish antiviral response during light exposure, which inherently involves modification of the expression of key components of the molecular circadian clock. It suggests that the zebrafish antiviral response to infection is regulated by both light and the circadian clock., Competing Interests: Declaration of competing interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Tilapia lake virus (TiLV) is a novel contagious pathogen associated with a lethal disease affecting and decimating tilapia populations on several continents across the globe. Fish viral diseases, such as Tilapia lake virus disease (TiLVD), represent a serious threat to tilapia aquaculture. Therefore, a better understanding of the innate immune responses involved in establishing an antiviral state can help shed light on TiLV disease pathogenesis. Moreover, understanding the adaptive immune mechanisms involved in mounting protection against TiLV could greatly assist in the development of vaccination strategies aimed at controlling TiLVD. This review summarizes the current state of knowledge on the immune responses following TiLV infection. After describing the main pathological findings associated with TiLVD, both the innate and adaptive immune responses and mechanisms to TiLV infection are discussed, in both disease infection models and in vitro studies. In addition, our work, highlights research questions, knowledge gaps and research areas in the immunology of TiLV infection where further studies are needed to better understand how disease protection against TiLV is established., Competing Interests: The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kembou-Ringert, Steinhagen, Thompson, Daly and Adamek.)

This paper discusses the possible use of 3D fused deposition modeling (FDM) to fabricate capillaries for low-cost chemiresistive gas sensors that are often used in various applications. The disadvantage of these sensors is low selectivity, but 3D printed FDM capillaries have the potential to increase their selectivity. Capillaries with 1, 2 and 3 tiers with a length of 1.5 m, 3.1 m and 4.7 m were designed and manufactured. Food and goods available in the general trade network were used as samples (alcohol, seafood, chicken thigh meat, acetone-free nail polish remover and gas from a gas lighter) were also tested. The "Vodka" sample was used as a standard for determining the effect of capillary parameters on the output signal of the MiCS6814 sensor. The results show the shift of individual parts of the signal in time depending on the parameters of the capillary and the carrier air flow. A three-tier capillary was chosen for the comparison of gas samples with each other. The graphs show the differences between individual samples, not only in the height of the output signal but also in its time characteristic. The tested 3D printed FDM capillaries thus made it possible to characterize the output response by also using an inexpensive chemiresistive gas sensor in the time domain.

DExD/H-box helicase (DDX) 5 belongs to the DExD/H-box helicase family. DDX family members play differential roles in the regulation of innate antiviral immune response. However, whether DDX5 is involved in antiviral immunity remains unclear. In this study, we found that DDX5 serves as a negative regulator of type I interferon (IFN) response. Overexpression of DDX5 inhibited IFN production induced by Spring viremia of carp virus (SVCV) and poly(I:C) and enhanced virus replication by targeting key elements of the RLR signaling pathway (MAVS, MITA, TBK1, IRF3 and IRF7). Mechanistically, DDX5 directly interacted with TBK1 to promote its autophagy-mediated degradation. Moreover, DDX5 was shown to block the interaction between TRAF3 and TBK1, hence preventing nuclear translocation of IRF3. Together, these data shed light on the roles of DDX5 in regulating IFN response., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Carp edema virus disease (CEVD), also known as koi sleepy disease (KSD), represents a serious threat to the carp industry. The expression of immune-related genes to CEV infections could lead to the selection of crucial biomarkers of the development of the disease. The expression of a total of eleven immune-related genes encoding cytokines (IL-1 β , IL-10, IL-6a, and TNF- α 2), antiviral response (Mx2), cellular receptors (CD4, CD8b1, and GzmA ), immunoglobulin (IgM), and genes encoding-mucins was monitored in gills of four differently KSD-susceptible strains of carp (Amur wild carp, Amur Sasan, AS; Ropsha scaly carp, Rop; Prerov scaly carp, PS; and koi) on days 6 and 11 post-infection. Carp strains were infected through two cohabitation infection trials with CEV genogroups I or IIa. The results showed that during the infection with both CEV genogroups, KSD-susceptible koi induced an innate immune response with significant up-regulation ( p  < 0.05) of IL-1 β , IL-10, IL-6a, and TNF- α 2 genes on both 6 and 11 days post-infection (dpi) compared to the fish sampled on day 0. Compared to koi, AS and Rop strains showed up-regulation of IL-6a and TNF- α 2 but no other cytokine genes. During the infection with CEV genogroup IIa, Mx2 was significantly up-regulated in all strains and peaked on 6 dpi in AS, PS, and Rop. In koi, it remained high until 11 dpi. With genogroup I infection, Mx2 was up-expressed in koi on 6 dpi and in PS on both 6 and 11 dpi. No significant differences were noticed in selected mucin genes expression measured in gills of any carp strains exposed to both CEV genogroups. During both CEV genogroups infections, the expression levels of most of the genes for T cell response, including CD4, CD8b1, and GzmA were down-regulated in AS and koi at all time points compared to day 0 control. The expression data for the above experimental trials suggest that both CEV genogroups infections in common carp strains lead to activation of the same expression pattern regardless of the fish's susceptibility towards the virus. The expression of the same genes in AS and koi responding to CEV genogroup IIa infection in mucosal tissues such as gill, gut, and skin showed the significant up-regulation of all the cytokine genes in gill and gut tissues from koi carp at 5 dpi. Significant down-regulation of CD4 and GzmA levels were only detected in koi gill on 5 dpi but not in other tissues. AS carp displayed significant up-expression of Mx2 gene in all mucosal tissues on 5 dpi, whereas in koi, it was up-regulated in gill and gut only. In both carp strains, gill harbored a higher virus load on 5 dpi compared to the other tissues. The results showed that resistance to CEV could not be linked with the selected immune responses measured. The up-regulation of mRNA expression of most of the selected immune-related genes in koi gill and gut suggests that CEV induces a more systemic mucosal immune response not restricted to the target tissue of gills., Competing Interests: The authors declare there are no competing interests., (©2023 Baloch et al.)

Context modulates sensory neural activations enhancing perceptual and behavioral performance and reducing prediction errors. However, the mechanism of when and where these high-level expectations act on sensory processing is unclear. Here, we isolate the effect of expectation absent of any auditory evoked activity by assessing the response to omitted expected sounds. Electrocorticographic signals were recorded directly from subdural electrode grids placed over the superior temporal gyrus (STG). Subjects listened to a predictable sequence of syllables, with some infrequently omitted. We found high-frequency band activity (HFA, 70-170 Hz) in response to omissions, which overlapped with a posterior subset of auditory-active electrodes in STG. Heard syllables could be distinguishable reliably from STG, but not the identity of the omitted stimulus. Both omission- and target-detection responses were also observed in the prefrontal cortex. We propose that the posterior STG is central for implementing predictions in the auditory environment. HFA omission responses in this region appear to index mismatch-signaling or salience detection processes., (© The Author(s) 2023. Published by Oxford University Press.)

Stereoelectroencephalography (SEEG) is a neurosurgical method to survey electrophysiological activity within the brain to treat disorders such as Epilepsy. In this stereotactic approach, leads are implanted through straight trajectories to survey both cortical and sub-cortical activity.Visualizing the recorded locations covering sulcal and gyral activity while staying true to the cortical architecture is challenging due to the folded, three-dimensional nature of the human cortex.To overcome this challenge, we developed a novel visualization concept, allowing investigators to dynamically morph between the subjects' cortical reconstruction and an inflated cortex representation. This inflated view, in which gyri and sulci are viewed on a smooth surface, allows better visualization of electrodes buried within the sulcus while staying true to the underlying cortical architecture.Clinical relevance- These visualization techniques might also help guide clinical decision-making when defining seizure onset zones or resections for patients undergoing SEEG monitoring for intractable epilepsy.

Metabolic reprogramming of cancer cells is a common hallmark of malignant transformation. The preference for aerobic glycolysis over oxidative phosphorylation in tumors is a well-studied phenomenon known as the Warburg effect. Importantly, metabolic transformation of cancer cells also involves alterations in signaling cascades contributing to lipid metabolism, amino acid flux and synthesis, and utilization of ketone bodies. Also, redox regulation interacts with metabolic reprogramming during malignant transformation. Flavonoids, widely distributed phytochemicals in plants, exert various beneficial effects on human health through modulating molecular cascades altered in the pathological cancer phenotype. Recent evidence has identified numerous flavonoids as modulators of critical components of cancer metabolism and associated pathways interacting with metabolic cascades such as redox balance. Flavonoids affect lipid metabolism by regulating fatty acid synthase, redox balance by modulating nuclear factor-erythroid factor 2-related factor 2 (Nrf2) activity, or amino acid flux and synthesis by phosphoglycerate mutase 1. Here, we discuss recent preclinical evidence evaluating the impact of flavonoids on cancer metabolism, focusing on lipid and amino acid metabolic cascades, redox balance, and ketone bodies., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

The slow discovery of new antibiotics combined with the alarming emergence of antibiotic-resistant bacteria underscores the need for alternative treatments. In this regard, fish skin mucus has been demonstrated to contain a diverse array of bioactive molecules with antimicrobial properties, including peptides, proteins, and other metabolites. This review aims to provide an overview of the antimicrobial molecules found in fish skin mucus and its reported in vitro antimicrobial capacity against bacteria, fungi, and viruses. Additionally, the different methods of mucus extraction, which can be grouped as aqueous, organic, and acidic extractions, are presented. Finally, omic techniques (genomics, transcriptomics, proteomics, metabolomics, and multiomics) are described as key tools for the identification and isolation of new antimicrobial compounds. Overall, this study provides valuable insight into the potential of fish skin mucus as a promising source for the discovery of new antimicrobial agents.