HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive neurological disorder and shares many radiological and clinical features with other more prevalent myelopathies. Here, we quantified spinal cord and brain volumes in adults with HAM/TSP in comparison with healthy volunteers (HVs) and participants diagnosed with multiple sclerosis (MS). Clinical disability and MRI were assessed in 24 HVs, 43 HAM/TSP, and 46 MS participants. Spinal cord cross-sectional area (SCCSA) and brain tissue volumes were measured and compared. HAM/TSP participants had significantly lower SCCSA at C2-3 (54.0±8 mm2), C4-5 (57.8±8 mm2), and T4-9 (22.7±4 mm2) and significantly elevated brain white matter hyperintensity (WMH) fraction (0.004±0.008) was compared to HVs (C2-3: 69.4±8 mm2, C4-5: 75.1±9 mm2, T4-9: 34.1±4 mm2; all p < 0.0001; and WMH: 0.0004±0.0007; p < 0.001). In HAM/TSP, SCCSA at all levels but not WMH showed the significant correlation with clinical disability scores. Brain white matter hyperintensities in HAM/TSP, therefore, may not be related to clinical disability. SCCSA and WMH in our limited MS cohort were higher than the HAM/TSP cohort (67.6±8 mm2, 72.7±9 mm2, 33.4±5 mm2; p < 0.0001). Principal component analysis suggested that SCCSA and WMH may be used to differentiated HAM/TSP from MS. Understanding these differences may help establish early diagnostic criteria for HAM/TSP patients.

Antisense oligonucleotides (ASOs) are short oligodeoxynucleotides designed to bind to specific regions of target mRNA. ASOs can modulate pre-mRNA splicing, increase levels of functional proteins and decrease levels of toxic proteins. ASOs are being developed for the treatment of several diseases, including motor neuron diseases (MNDs), a group of neurodegenerative disorders characterised by the loss of motor neurons, including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA). The biggest success has been the ASO known as nusinersen, the first effective therapy for SMA, able to improve symptoms and slow disease progression. Another success is tofersen, an ASO designed to treat ALS patients with SOD1 gene mutations. Both ASOs have been approved by the FDA and EMA. On the other hand, ASO treatment in ALS patients with the C9orf72 gene mutation did not show any improvement in disease progression. The aim of this review is to provide an up-to-date overview of ASO research in MND, from preclinical studies to clinical trials and, where available, regulatory approval. We highlight the successes and failures, underline the strengths and limitations of the current ASO research, and suggest possible approaches that could lead to more effective treatments.

Transactive response DNA-binding protein of 43 kDa (TDP-43) is a major component of pathological inclusions in various neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). The detection of TDP-43 in biofluids is crucial for the development of diagnostic and prognostic indicators of disease and therapeutic development for TDP-43 related proteinopathies. Despite its potential as a biomarker for numerous neurological disorders, the lack of a sensitive and reproducible TDP-43 assay hinders progress in TDP-43-based therapy development, underscoring the need for an effective and standardized method for accurate quantification. In this study, we developed and validated a sensitive immunoassay for the detection of TDP-43 in human biofluids using the Meso Scale Discovery (MSD) platform. We used this immunoassay to quantify TDP-43 levels in the plasma and serum of healthy controls and ALS patients. Our results indicate a reduction of total TDP-43 in the blood of ALS patients compared to healthy controls.

The prevalence of sexual harassment and abuse in school sport, specifically from coaches to their athletes remains a concerning and pervasive issue. In an attempt to better understand and prevent specific coach-behaviours associated with such sexual misconduct, researchers have developed the Sexual Violence Questionaire in Sport. While the reliability of this measurement tool has been tested in anglo-saxon cultural contexts, it is not known whether the questionnaire is applicable to other cultural contexts. A sample of 146 (52 female, 94 male) Bachelor students from a university in the Basque Country participated in this cross cross-sectional study. The questionnaire was administered twice over a two-week period to assess test-retest reliability. The internal consistency of the Sexual Violence Questionaire in Sport was high, with Cronbach's alpha values of 0.891 for perceptions and 0.813 for experiences across all participants. Gender-specific analysis showed similar reliability, with females having slightly lower alpha values for perceptions. Significant differences between test and retest were found (10 from perceptions 2 from experiences). However, Cohen’s Kappa analysis showed significant agreement across all items. In conclusion, the study highlights the questionnaire’s overall reliability and suggests its effectiveness as a tool for measuring sexual violence in sports within the Spanish context. Nonetheless, the findings of this study underscore the need for further research to enhance the instrument's stability and to better understand gender differences in perceptions and experiences of sexual violence in sports contexts.

Background:In view of fact, the drawback of the armed conflict between Sudanese army and rapid support force was shocking, mass migration to neighboring countries, and many civilian were died, behind the war there were another factors for death, among these factors is brain tumors. The objectives of this study: To build up information and correlation between demographic data, brain tumors, surgery type and limitation of surgical resources, and to identify neurosurgical practice during armed conflict and how surgical resources can be utilized. Methods:This was a case report study, done at Almubarik hospital from April 2024 to July 2024.Ethical approval was taken from the National Center for Neurological Sciences.The operating room at Almubarik hospital includes X-ray viewing box, operating table, which is design for obstetrical and gynecology operation. very limited instruments for completing the surgery (forceps, straight dissector and scissors).Moreover, regarding anesthesia in this new situation there is no invasive BP, CVP, core temperature or even capnograph, all this made difficulties in monitoring the patient. In this conflict period, due to the lake of monitoring of the drugs and inappropriate storage, we used to give IV propofol , midasolam , morphine , lidocaine and nondepolrising muscle relaxant. ETT size 7 for all adult patients as it is the only big size available. Halothane MAC was used as volatile agent with propofol. pracetamol , magnisum sulphate ,are given as analgesia.Nevertheless,, for positing we manipulate our operating table by adding special head rest which was manually made from iron par and semi firm bellows are constructed on it tightly, so prone position was made. Conclusion: Despite of the infrastructural limitations, brain tumor surgery has special nature in the context of this conflict. Brain tumor surgery is challenges, and need not only skillful neurosurgeon but advance technology and well trained staff.

Background/Objectives: Intracranial Epidermoid Cysts (IECs) are extremely rare intracranial tumors. The primary treatment is surgery; however, cyst adherence results in difficult removal; subtotal resection yields high recurrence rates. The mechanisms of IECs remain unknown, consequently, advances in treatment have fallen short. Tumor genetic profiling has rendered targets for drug development and for which FDA-approved options exist, reshaping cancer treatment. The genetics of IECs has not been explored. We applied Whole Exome Sequencing (WES) in IECs to gain insights into the mechanisms of oncogenesis and identify actionable targets. Methods: We performed WES in tumor tissue and matching blood, when available. Read processing, quality control and somatic variant calling followed GATK best practices. Read alignments were also used for somatic copy-number inference. Data analyses and visualizations were conducted in R. Results: Top altered genes were associated with immune system and microenvironment, suggesting an immune evasion mechanism. Recurrent and deleterious NOTCH2 and USP8 alterations were identified in 50% and 30% of the cohort, respectively. Frequent amplifications in deubiquitinases and beta-defensins, strengthened the involvement of an immune mechanism for oncogenic transformation. Drug-gene interactions highlighted NOTCH2 as clinically relevant for which FDA-approved treatments exists. Conclusions: Top altered genes may have a role in shaping an epidermoid cyst-permissive tumor microenvironment and modulating tumor immune evasion. USP8 and NOTCH2 may be clinically relevant drivers of IECs. NOTCH2 may be an interesting candidate for drug repurposing.

Introduction Meningioma is the second most common primary intracranial tumor of the central nervous system. in Sudan, meningioma is the most common primary brain tumor, among Sudanese patients, Surgical total excision of meningioma offers a better survival, however, Chemotherapy has largely been unsuccessful for meningioma treatment, and therefore, refractory and recurrence meningioma treated with palliative surgery and radiotherapy. Monosomy of chromosome 22 is the utmost common genetic alteration among meningioma and many genes were investigated and described in the development of this tumor of which , NF2 hSNF5/INI1gene, P53. In addition to this, Molecular signal pathways in meningioma, and that contribute to the survival, proliferation, self-renewal, and differentiation properties of normal stem cells which are abnormally activated and nominated as cancerous stem cell (CSCs). Objectives 1/ To identify the possible pathway of candidate genes in both setting and whole genes hypothesis free approach 2/ To assess the presence of mutations in candidate genes among histological subtypes of meningioma in Sudan. Material and methods This is a prospective cross-sectional study done at the National Center of Neurological Sciences (NCNS) Khartoum, from 2018 to 2021. The study included all cerebral tumors that were radio- logically diagnosed preoperatively as meningioma. Ethical approval was taken from Institute of Endemic disease, Khartoum University, and written consent was obtained Three DNA extracts were randomly selected from 20 meningioma tissue samples and processed for WES. All genes harboring exonic and splice site variations stratified into SNVs and INDELs sets were prepared. The 1000G online database was used to explore novel mutations per 3 samples. SIFT and PolyPhen-2 programs were used to predict possible impact of amino acids substitution. To address meticulous genes interaction and particular centrality, all shared genes within the class INDEL and SNVs were used as input on Network Analysis to predict protein- protein interaction and functional gene ontology. Finally, shared mutations within genes of centrality were detected via Sanger sequencing and mutations were correlated between histological sub-types and recurrenceThree non meningioma brain tumor used as control. Results WES analysis revealed high number for mutational signature within 2 classes (INDEL and SNVs) per 3 samples, the findings of 1000 genome online database showed number of novel mutations; 5618 in fibrous , 6032 in meningothelial while in recurrent fibrous sample 5930. Network analysis of shared genes per each class (INDEL, SNVs), showed UBC is the most protein of remarkable degree centrality over thousand of genes. Whereas, all shared genes per 3 samples within the 2 classes (INDEL and SNVs) revealed Akt1 with the highest degree of centrality and betweenness. Akt1 rs17846829was detected in 20% of the samples, while CD44 stemness gene revealed mutation A>G (rs9666607) in all meningioma samples (100%), this mutation was associated with 60% of the recurrence. Conclusions Nevertheless, the present study, highlight how such complex molecular processes might contribute to tumorogenesis, in attempt to shed light over thousands of genes and multifaceted network analysis rather than a solitary gene which is challenging question.

Introduction: The association between epilepsy and myasthenia gravis has rarely been reported, and only in small case series. Objective: To report the frequency of epilepsy and myasthenia gravis and to describe a case series of patients with myasthenia gravis and epilepsy, focusing on their clinical characteristics and searching for a possible physiopathological mechanism. Methods: A retrospective, observational, adult center study was conducted in 2022. Patients were recruited from the database of the outpatient clinic of the Myasthenia Gravis unit and Epilepsy unit. Results: Five patients were included. Frequency of epilepsy in the myasthenia gravis cohort was 5/469 (1.1%), and of myasthenia gravis in the epilepsy cohort was 5/1432 (0.35%). All patients suffered focal epilepsy, mainly fronto-central, and drug-resistant in half of them. Myasthenia gravis was generalized and with exacerbations in half of them. Three patients were thymectomized. Other autoimmune diseases were found in 2 (40%). Epilepsy onset preceded myasthenia gravis onset in all patients. Both diseases were considered autoimmune-related in 3/5 (60%). Conclusion: Epilepsy and myasthenia gravis are only infrequently associated. In adult patients, epilepsy onset precedes myasthenia onset in most cases. In some cases, epilepsy has an autoimmune aetiology and coexists with other autoimmune conditions.

Myeloperoxidase (MPO) is an enzyme that contains a heme group, found mostly in neutrophils and in small amounts in monocytes and plays a major role in their anti-microbial activity. However, excessive levels of MPO have been linked to various disorders and identified as a major cause of tissue destruction. Inhibiting its activity can reduce the severity and extent of tissue damage. Over activity of MPO during chronic inflammation has been shown to be involved in tumorigenesis by inducing a hyper-mutagenic environment through oxidant interaction with DNA, causing DNA modification. Vascular endothelium is one of the most important targets of MPO and high levels have been associated with increased rates of cardiomyopathy, ischemic stroke, heart failure, myocardial infarction, and atrial fibrillation. Therefore, it may be considered a therapeutic target in the treatment of cardiovascular disorders. MPO also participates in the pathogenesis of neurodegenerative diseases. For example, an increase in MPO levels has been observed in the brain tissue of patients with Alzheimer's, Multiple sclerosis (MS), and Parkinson's diseases. In Alzheimer's disease, active MPO is mostly found in the location of beta amyloids and microglia. Therefore, targeting MPO may be a potential treatment and prevention strategy for neurological disorders. This review will discuss MPO's physiological and pathological role in cancer, cardiovascular, and neurological disorders.

This study proposed to use wearable EEG to study the impact of vipassana mindfulness practice on beginner's physiological and neurological responses. Mindfulness meditation has been shown to have numerous benefits, including stress reduction, improved attention and cognitive function, and enhanced emotional regulation. The roots of mindfulness meditation in Buddhism emphasize cultivating present-moment awareness and insight. However, the neural mechanisms together with physiological mechanism and their interaction underlying these benefits remain poorly understood. Method: One middle age man (50 years old) participated in this longitudinal study using wearable EEG to investigate the neurophysiological change during a one-month consecutive vipassana mindfulness practice. Both EEG and heart rate responses were recorded each time, before (5 minutes), during (20 minutes), and after (5 minutes) meditation sessions. The EEG and HR data were analyzed by Matlab and EEGlab to examine changes in brainwave activity and heart rate. Results: alpha peak frequency (APF) is significantly lower after mindfulness meditation, as shown by comparison of APF before mindfulness (pre-5) and during mindfulness practice (med-20), and comparison between APF of pre-5 and after mindfulness practice (post-5). The same is with the beta peak power. While for theta peak frequency, it is significant lower during mindfulness meditation (med-20), when comparing to either pre-5 or post-5. See figure 1a. However, peak power index is not so sensitive, and it is more obvious in theta wave band. That is, the theta power peak is significantly lower after meditation, as can be observed in comparison between pre-5 and med-20, also between pre-5 and med-20. See figure 1b. STATE Heart-mean (bpm) Heart-std(bmp) pre-5 69.88 3.88 med-20 68.36 2.81 post-5 69.55 4.13 t-value test (pre-med) 0.0694 0.0003 t-value test (pre-post) 0.7934 0.3656 t-value test (post-med) 0.3193 0.0001 Table 1. The difference of Heart rate (mean and SD) in before (pre-5), during (med-20) and after (post-5)mindfulness meditation. We find significant change in standard deviation (SD) of heart rate between meditation and non-meditation mental states, as shown in table 1. The study provides insights into the underlying neurophysiological mechanisms of mindfulness meditation using wearable EEG devices. It demonstrates that in term of EEG measurement, spectrum frequency can be more sensitive than spectrum power; also heart rate variability as measured by SD is more sensitive to mean of HR. The proposed study contributes to the literature by using wearable EEG devices to collect data in a more accessible and convenient manner.

Functional neurological disorder, or FND, is widely misunderstood, particularly when considering recent research that suggests that the illness has a biological rather than a psychiatric basis. Nonetheless, the long-held view that FND is a purely psychiatric disorder without biological basis, or even a contrived (malingered) illness, remains pervasive both in modern medical care and general society. This is because FND involves an intermittent course of involuntary disability that rapidly alternates with improved neurological control. This has in turn caused shaming, low self-efficacy, and social isolation of the patients. Little research has examined the numerous biomarkers that are shared between FND and canonical neurological disorders and the encouraging outcomes that can follow conventional neurological rehabilitation, modified for this disorder. This review summarizes current research on FND biomarkers and physical rehabilitation results. General healthcare providers would benefit their care for their patients through their improved understanding the illness and recourses for support and treatment that are provided in this review.

Background: Pediatric neurological disorders include neurodegenerative disease causing cognitive impairment, vision loss to mention a few. They are one of the important causes of morbidity and mortality in children with diverse etiology. Diagnosis is difficult in spite of genetic work and in only 60% of cases final diagnosis can be achieved. Case presentation: We explore three cases of pediatric neurological diseases, viz. Arthrogryposis, congenital bilateral cataract and Autism by analyzing clinical exomes. In this work, we attempted to understand rare neurological disorders in an Indian pediatric cohort using exome studies. Conclusions: We used our benchmarked CONVEX pipeline for screening consensus variants, wherein EIF2B2 was found to be inherently pathogenic. We map the association of variants and genes, disease correlation to neuroleptic malignant syndrome which is a matching phenotype to the cases.

Neural membranes are composed of phospholipids, sphingolipids, cholesterol and proteins. In re-sponse to cell stimulation or injury, metabolism of lipids generates various lipid mediators, which perform many cellular functions. Thus, phospholipids release arachidonic acid or docosahex-aenoic acid from the sn-2 position of glycerol moiety by the action of phospholipases A2. Ara-chidonic acid is a precursor for prostaglandins, leukotrienes, thromboxane, and lipoxins. Among these mediators, prostaglandins, leukotrienes, and thromboxane produce neuroinflammation. In contrast, lipoxins produce anti-inflammatory and pro-resolving effects. Prostaglandins, leukotri-enes, and thromboxane are also involved in cell proliferation, differentiation, and blood clotting, and blood vessel permeability. In contrast, DHA-derived lipid mediators are called as specialized pro-resolving lipid metabolites (SPMs). They include resolvins, protectins, and maresins. These mediators regulate immune function by producing anti-inflammatory, pro-resolving, and cell pro-tective effects. Sphingolipid derived-metabolites are ceramide, ceramide1-phosphate, sphingosine, and sphingosine 1 phosphate. They regulate many cellular processes including enzyme activities, cell migration and adhesion, inflammation, and immunity. Cholesterol is metabolized into hy-droxycholesterols and 7-ketocholesterol, which not only disrupts membrane fluidity, but also promotes inflammation, oxidative stress, and apoptosis. These processes lead to cellular damage.

The most recent and non-invasive approach for studying early-stage biomarkers is liquid biopsy. It implies the extraction and analysis of non-solid biological tissues (serum, plasma, saliva, urine and cerebrospinal fluid) without undergoing invasive procedures to determine disease prognosis. Liquid biopsy can be used for the screening of several components such as extracellular vesicles, microRNAs, cell-free DNA, cell-free mitochondrial and nuclear DNA, circulating tumor cells, circulating tumor DNA, transfer RNA and circular DNA or RNA derived from body fluids. Its application includes early disease diagnosis, surveillance of disease activity, and treatment response monitoring, with growing evidence for validating this methodology in cancer, liver disease, and central nervous system (CNS) disorders. This review will provide an overview of mentioned liquid biopsy components, which could serve as valuable biomarkers for the evaluation of complex neurological conditions, including Alzheimer’s disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, stroke, traumatic brain injury, CNS tumors, and neuroinfectious diseases. Furthermore, this review highlights the future directions and potential limitations associated with liquid biopsy.

To verify the efficacy of placental extracts (Pla-Ext) and human mesenchymal stem-cell-derived exosomes (hMSC-Exo) against human skin aging, we investigated the human dermal fibroblast (HDF) response following hMSC-Exo and Pla-Ext treatment and whether they elicited resistance to damage when HDFs were subjected to several types of aging stresses. The effect of hMSC-Exo alone, the combined effect of Pla-Ext and hMSC-Exo, and the effect of hMSC-Exo (Pla/MSC-Exo) recovered from cultures with Pla-Ext added to hMSC were verified using collagen, elastin, and hyaluronic acid synthase mRNA levels for each effect. Cells were subjected to photoaging (UV radiation), glycation (glycation end product stimulation), and oxidation (H2O2 stimulation) as HDF stressors. Pla-Ext did not significantly affect normal skin fibroblasts considering intracellular parameters; however, a pro-proliferative effect was observed. Pla-Ext induced resistance to several stresses in skin fibroblasts (UV irradiation, glycation stimulation, H2O2 stimulation) and inhibited reactive oxygen species accumulation following H2O2 stimulation. Although the combined efficacy of hMSC-Exo and Pla-Ext was unclear, some changes resulted in senescence stress resistance due to preconditioned hMSC-Exo stimulated by Pla-Ext. This suggests that Pla-Ext supplementation may cause some changes in the surface molecules or hMSC-Exo content (e.g., microRNA).

Poverty has long been associated intricately with neurological disorders. Majority of the previous studies designed to describe the effects of poverty on neurological ailments have mostly linked the association of hypoxic ischemic encephalopathy and nutritional deficiency disorders with poverty. Authors herein try to delve deeper into this issue. The association of begging with neuropsychiatric disorders is robust. The burden of probable autosomal dominant neurological ailments is very common among beggars; followed by neurological disorders with social stigma like abnormal movements, facial dysmorphism and gait unsteadiness. Dearth of support from family members in autosomal dominant neurological disorders (as family members are likely to be suffering from similar neurodegenerative disorder ) and poor perception about neurological diseases, misconceptions, myths and low educational attainment at large in the society can be implicated as the often overlooked but important factors underneath this association of begging and neurological disorders.

Handedness reflects functional body and hemispheric lateralization, proving relevant to contextualize cognitive and behavioral profiles. This study aimed to determine the lateralization of the hands, feet and eyes in patients with various neurological disorders and to test the Edinburgh Handedness Inventory (EHI), a widely used handedness measure. The study design included a literature overview and a clinical study. The overview spanned the literature of the past 50 years since the EHI was developed. Three hundred seventy-four patients with immune-mediated (IM) or noIM neurological diseases and healthy subjects underwent personal and family history of handedness, stressful events and IM diseases, and EHI. The literature overview showed that handedness, which develops under the influence of genetic and acquired factors, is an indirect indicator of hemispheric lateralization; hemispheric lateralization is bidirectionally related to the immune system. In the clinical study, the EHI showed appropriate reliability and structural validity; its scores related to chronological age, onset age, and disease duration and helped distinguish patients with IM disease from other patients and healthy subjects. Therefore, handedness may change over the course of life under the influence of pathology and could predict IM neurological diseases. The EHI is an appropriate measure of handedness.

While the desire to uncover the neural correlates of consciousness has taken numerous directions, self-face recognition has been a constant in attempts to isolate aspects of self-awareness. The neuroimaging revolution of the 1990’s bought about systematic attempts to isolate the underlying neural basis self-face recognition. These studies, including some of the first fMRI (functional Magnetic Resonance Imaging) studies, revealed a right hemisphere bias for self-face recognition in a diverse set of regions including the insula, the Dorsal Frontal Lobe, the Temporal Parietal Junction and Medial Temporal Cortex. Confirmation of these data (which are correlational) was provided by TMS (Transcranial Magnetic Stimulation) and patients in which direct inhibition or ablation of right hemisphere regions leads to a disruption or absence of self-face recognition. These data are consistent with a number of theories including a right hemisphere dominance for self-awareness and/or a right hemisphere specialization for identifying significant social relationships including to oneself.

Embryologically, the left brachiocephalic vein (LBV) originates as an anastomotic channel between the right and left anterior cardinal veins 1 . This positions the LBV between the manubrium sterni anteriorly and the innominate artery posteriorly 2 . This pattern of adjacency of the aorta to the LBV is unique to mammals and results from a quirk of evolution 3 . With age, the ascending aorta unfolds, elongates and dilates 4 . Simultaneously, there is a change in the thoracic geometry that reduces the thoracic volume primarily from disc height loss and kyphosis 5 . These transitions progressively compress the LBV. Normally this compression is circumvented via collateral pathways and "Blood finds a way" 6 . However, traversing these circuitous pathways comes at a cost and can result in delayed transit times and venous congestion. While it is possible that compression of the LBV in the setting of adequate collateral channels may fail to provoke any pathologic sequelae, we propose a phenomenon in which such compression in the setting of inadequate collateral circulation may lead to a state of pathologic venous congestion. This anatomic anomaly and its associated clinical features, if identified, can offer a new avenue for treatment options for some of the hitherto unexplained neurologic disorders.

Neurological / neurovascular disorders constitute the leading cause of disability and second leading cause of deaths in the world. Some of the major neurological / neurovascular disorders or diseases include stroke, Alzheimer’s disease, spinal cord injury, neonatal hypoxic-ischemic encephalopathy, etc. Their pathophysiology is considered as highly complex and has been blamed as the main obstacle in the development of any drugs for these diseases. In this review, we have described the endothelin system, their involvement in neurovascular disorders, importance of endothelin B receptors (ETBRs) as a novel potential drug target, and its agonism by IRL-1620 (INN - sovateltide), which we are developing as a drug candidate for treating the above-mentioned neurological disorders / diseases. We have highlighted the results of our pre-clinical and clinical studies related to these diseases. The phase I, safety and tolerability study of sovateltide has shown it as a highly safe and well tolerable compound at tested dosages, while pre-clinical and clinical phase II studies have demonstrated its efficacy in treating acute ischemic stroke, where it is currently being developed as a “First in Class” drug. Its testing in Alzheimer’s disease (AD), acute spinal cord injury and neonatal hypoxic-ischemic encephalopathy (HIE) is currently being carried out and are at different stages of drug development. Successful completion of these studies will prove the involvement of ETBRs signaling in neurological / neurovascular diseases and help in development of novel neurological drugs in future.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease that affects about 1% of the global population, with a female-male ratio of 3:1. To date, genetic predisposition, the involvement of a deficient immune system and lifestyle are known to be the major responsible for the onset of the disease. RA preferably affects the joints, with consequent joint swelling and deformities followed by ankylosis. Patients suffering from rheumatoid arthritis can also develop extra-articular manifestations, which mainly affect the cardiovascular system, the nervous system, the skin, the eye, the respiratory system, the kidney and the gastrointestinal system. It has been shown that about 20% of RA patients can develop neuropathies, multiple mononeuritis, distal sensory neuropathies and sense motor neuropathies. Neurological involvement occurs as a consequence of vasculitis of the nerve vessels leading to vascular ischaemia, axonal degeneration and neuronal demyelination. In RA, the risk of developing cardiovascular disease is very high and depends, most probably, on vascular damage resulting from endothelial dysfunction. Hence, it is reasonable to assume that the integrity of the endothelium is also involved in the neurological disorders resulting from RA. This review aims to highlight the main characteristics of the extra-articular manifestations at the nervous level resulting from rheumatoid arthritis. To this end, the literature main results on these pathological manifestations have been collected with particular focus on the involvement of endothelial dysfunction. In fact, the endothelium could be considered a valuable target for minimizing the incidence of extra-articular neurological manifestations in RA.

The Coronavirus disease due to SARS-CoV-2 emerged in Wuhan city, China in December 2019 and rapidly spread more than 200 countries as a global health pandemic. There are more 3 million confirmed cases and around 207,000 fatalities. The primary manifestation is respiratory and cardiac but neurological manifestations are being reported in the literature as case reports and case series. The most common reported symptoms to include headache and dizziness followed by encephalopathy and delirium. Among the complications noted are Cerebrovascular accident, Guillian barre syndrome, acute transverse myelitis, and acute encephalitis. The most common peripheral manifestation was hyposmia. It is further noted that sometimes the neurological manifestations can precede the typical features like fever and cough and later on typical manifestations develop in these patients. Hence a high index of suspicion is required for timely diagnosis and isolation of cases to prevent the spread in neurology wards. We present a narrative review of the neurological manifestations and complications of COVID-19. Our aim is to update the neurologists and physicians working with suspected cases of COVID-19 about the possible neurological presentations and the probable neurological complications resulting from this novel virus infection.

Prenylated flavonoids of Humulus lupulus L. have gained attention for their potential health benefits. In this study, Amber ALE and Russian Imperial Stout beers were prepared. In order to increase the content of prenylated flavonoids in beer, there was added ethanol extract of Polaris hops, they were dry hopping with Polaris hops or pure xanthohumol was added. In unfiltered beers, the highest total content of polyphenols (3.60 ± 0.32 g/L gallic acid) was determined on the eighth day of fermentation and maturation in Amber ALE beer without the addition of extract. The highest total antioxidant capacity was determined in Russian Imperial Stout beer with the addition of xanthohumol on the eighth day of fermentation and maturation (0.675 ± 0.008 mmol/L Trolox). This type of beer also had a high antioxidant efficiency (85.96 - 88.00%). Xanthohumol (2.05 mg/L) and isoxanthohumol (2.819 mg/L) were detectable only until the thirteenth day of fermentation and beer maturation. Therefore, the beers were filtered, and the ethanol extract of the Polaris was added to them for 24 hours. This procedure was used to prepare a functional beer of the Amber ALE type (15.210 ± 0.053 mg xanthohumol in 1 L and 0.922 ± 0.077 mg isoxanthohumol in 1 L) and a functional beer of the Russian Imperial Stout type (32.375 ± 0.032 mg xanthohumol in 1 L and 1.877 ± 0.043 mg isoxanthohumol in 1 L).

Brucellosis is a multi-system infectious disease that exhibits with various manifestations and complications. Neurobrucellosis is a rare but serious presentation of brucellosis that can be discovered in every stages of the disease. Laboratory tests and physical examination and patient history are generally the basis for diagnosing the disease. It has both insidious and prolonged clinical course of the disease and long-term therapies. Also the most common pattern of exhibition is subacute or chronic. We reported a case of young female who had history of painless weakness in the right lower limb (proximal and distal) that started gradually and had progressed over the time, and after a month she felt weakness in the left lower limb with the same pattern. Lumbosacral Magnetic resonance imaging (MRI) with and without contrast was shown evidence of enhancement thickening of caudal equina ventral roots. Brucella antigen titer was positive, the result was 1/160. And other clinical tests were normal. Patient treated with Intravenous injection (IV) Rifampicin and Intravenous Cotrimoxazole. patient was discharged with good health and continuinng all two medications for 5 months. The descision was taken to report this case as a result of entire respond in patient’s illness after a enduring disease. Neurobrucellosis is a treatable disease in which it would be better to consider a high indication of suspicion. Due to if ignored, it may cause significant morbidity and mortality.

Neurotrophins, particularly brain-derived neurotrophic factor (BDNF), act as key regulators of neuronal development, survival and plasticity. In this review, we focus on the role of BDNF for corticostriatal plasticity in movement disorders, including Parkinson’s Disease (PD) and dystonia. We discuss the mechanisms how dopaminergic input modulates BDNF/TrkB signaling at corticostriatal synapses and the involvement of these mechanisms in neuronal function and synaptic plasticity. Disruption of these pathways can lead to aberrant plasticity, ultimately affecting motor function. Advancing our understanding of these mechanisms could pave the way towards innovative therapeutic strategies aiming at restoring neuroplasticity and enhancing motor function in these diseases.

Diffuse intrinsic pontine glioma (DIPG) is recognized as a pediatric brainstem cancer with a 0% survival rate. On a molecular basis, DIPG commonly results from mutations in histone H3, specifically a mutation in the H3K27M gene, that promotes tumorigenesis and results in presentation of this fatal brainstem tumor. DIPG is challenging to treat, as surgical intervention is inefficacious due to the location where the glioma resides. To date, traditional treatments such as radiation, chemotherapy, and immunotherapy have not increased survival rates and have only been successful at relieving symptoms. Future therapeutic approaches such as proton beam radiation, Chimeric Antigen Receptor T Cell (CAR-T) immunotherapy, and alternative epigenetic pharmaceuticals are under investigation for potential benefits. Various clinical trials have also explored these treatment procedures to discover potential increases in survival rates in both animal and human studies. In this review, we will evaluate the pathology and molecular characteristics of DIPG, the current and future approaches to DIPG treatment; and, lastly, we will discuss clinical trials that have been completed to develop successful treatment options.

Antimicrobial peptides represent a promising alternative to traditional drugs in relation to cost, toxicity and, primarily, the growing problem of drug resistance. Here we report on the activity against HSV-1 and HSV-2 of a previously described wide-spectrum synthetic decapeptide, Killer Peptide (KP). As determined by plaque reduction assays, treatment with KP at 100 μg/mL resulted in a reduction in the viral yield titer of 3.5 Logs for HSV-1 and 4.1 Logs for HSV-2. Further evaluation of KP antiviral activity focused on the early stages of virus replicative cycle, including the determination of the residual infectivity of viral suspensions treated with KP. A direct effect of the peptide on viral particles, impairing virus absorption and penetration, was shown. The toxicity profile proved to be extremely good with a selectivity index of 29.6 for HSV-1 and 156 for HSV-2. KP was also active against an acyclovir (ACV)-resistant HSV-1 strain, while HSV-1 subcultures in the presence of sub-inhibitory doses of KP did not lead to the emergence of resistant strains. Finally, the antiviral action of KP proved to be synergistic with that of ACV. Overall, these results demonstrate that KP could represent an interesting addition/alternative to acyclovir for antiviral treatment.

The aim of this study was to investigate the physicochemical characterization and biological activities of chitosan (CH) based composite films with the incorporation of chestnut flower essential oil (CFEO). The composite films were prepared by casting method and characterized in terms of structural, morphological and mechanical properties via FT-IR, XRD, UV, SEM and TGA. The results proved the significantly increased water vapor permeability (WVP), heat resistance, antibacterial and antioxidant capabilities of CH-CFEO films. The incorporation of CH and CFEO enhanced the UV blocking, which made the film shield almost all UV light. Films with the tensile strength of 6.37 ± 0.41 MPa and elongation at break of 22.57 ± 0.35% were got with 6 mg mL-1 CFEO. Subsequently, the fruit preservation experiments also confirmed that the composite films could effectively extend the shelf life of bananas through their excellent water vapor and oxygen barrier. These desirable performances enable our newly developed composite films to be a remarkable packaging material to solve the fresh fruit preservation dilemma.

Stenting is an alternative to endarterectomy for the treatment of carotid artery stenosis. However, stenting is associated with a higher risk of procedural stroke secondary to distal thromboembolism. Hybrid stents with a micromesh layer have been proposed to address this complication. We developed a micropatterned thin film nitinol (M-TFN) covered stent designed to prevent thromboembolism during carotid intervention. This innovation may obviate the need or work synergistically with embolic protection devices. The proposed double layered stent is low-profile, thromboresistant, and covered with a M-TFN that can be fabricated with fenestrations of varying geometries and sizes. The M-TFN was created in multiple geometries, dimensions, and porosities by sputter deposition. The efficiency of various M-TFN to capture embolic particles was evaluated in different atherosclerotic carotid stenotic conditions through in vitro tests. The covered stent prevented emboli dislodgement in the range of 70-96% during 30min duration tests. In vitro vascular cell growth study results showed that endothelial cell elongation, alignment and growth behaviour silhouettes significantly enhance specifically on the diamond-shape M-TFN with the dimensions of 145µm×20µm and a porosity of 32%. Future studies will require in-vivo testing. Our results demonstrate that M-TFN has a promising potential for carotid artery stenting.

Psychotherapy is a comprehensive biological treatment modifying complex underlying cognitive, emotional, behavioral, and regulatory responses in the brain, leading patients with mental illness to a new interpretation of the sense of self and others. Psychotherapy is an art of science integrated with psychology and/or philosophy. Neurological science studies the neurological basis of cognition, memory, and behavior as well as the impact of neurological damage and disease on the functions, and their treatment. Both psychotherapy and neurological science deal with the brain; nevertheless, they continue to stay polarized far. Existential phenomenological psychotherapy (EPP) has been in the forefront of meaning-centered counseling for almost a century. The phenomenological approach in psychotherapy originated in the works of Martin Heidegger, Ludwig Binswanger, Medard Boss and Viktor Frankl, and it has been committed to account for the existential possibilities and limitations of one’s life. EPP provides philosophically rich interpretations and empowers counseling techniques to assist mentally suffering individuals by finding meaning and purpose of life. The approach has proven to be effective in treating mood and anxiety disorders. This narrative review article demonstrates the development of EPP, the therapeutic methodology, evidence-based accounts of its curative techniques, current understanding of mood and anxiety disorders in neurological science, and a possible converging path to translate and integrate meaning-centered psychotherapy and neuroscience, concluding that the existential phenomenological psychotherapy potently plays a synergistic role with the currently prevailing medication-based approaches for the treatment of mood and anxiety disorders.

Advances in diagnostic procedures have led to an increasing rate of diagnosis of autoimmune encephalitis or paraneoplastic neurological syndrome (AE/PNS) among patients with progressive supranuclear palsy (PSP)-like manifestations. The antibodies involved in these conditions include anti-IgLON5, -Ma2, and -Ri antibodies, each of which has a characteristic clinical presentation. The steps in the diagnosis of AE/PNS in patients with PSP-like manifestations include (i) suspicion of AE/PNS based on clinical presentations atypical of PSP and (ii) antibody detection measures. Methods used to identify antibodies include a combination of tissue-based assays and confirmatory tests. The primary confirmatory tests include cell-based assays and immunoblotting (line or western blot). Treatments can be divided into immunotherapy and tumor therapies, the former of which includes acute and maintenance therapies comprising corticosteroids, intravenous immunoglobulins, plasmapheresis, rituximab, and cyclophosphamide. One of the major challenges of diagnosis is that existing reports on PSP-like patients with AE/PNS include only case reports, with the majority discussing antibodies other than anti-IgLON5 antibody. As such, more patients need to be evaluated to establish the relationship between antibodies and PSP-like manifestations.

The integration of genetic technologies into neurological diagnostics has significantly enhanced our ability to understand and manage neurological disorders. This article discusses the functional analysis of key genetic tests, including microarray analysis, variant sequencing, exome sequencing, RNA sequencing, and whole genome sequencing. Each of these technologies offers unique advantages and challenges, providing a comprehensive toolkit for diagnosing and understanding the genetic basis of neurological conditions. The functional insights gained from these tests not only detect genetic abnormalities but also elucidate their functional consequences, aiding in the diagnosis, prognosis, and management of neurological disorders. As these technologies continue to evolve, they are expected to play an increasingly important role in the field of neurological diagnostics, paving the way for personalized medicine and improved patient outcomes.

Mild traumatic brain injuries (mTBIs) are highly prevalent and can lead to chronic behavioral and cognitive deficits, often associated with the development of neurodegenerative diseases. The formation of reactive oxygen species (ROS) and oxidative stress have been implicated in mTBI-mediated axonal injury and pathogenesis. However, the underlying mechanisms and contributing factors are not completely understood. In this study, utilizing a murine model of repetitive mTBI (r-mTBI) involving five closed-skull concussions in young adult C57BL/6J mice, we observed a significant elevation of Na+/H+ exchanger protein (NHE1) expression in GFAP+ reactive astrocytes, IBA1+ microglia, and OLIG2+ oligodendrocytes across various brain regions (including the cerebral cortex, corpus callosum, and hippocampus). This elevation was accompanied by astrogliosis, microgliosis and the accumulation of amyloid precursor protein (APP). Concurrently, r-mTBI mice displayed impaired motor learning and spatial memory deficits. However, post-r-mTBI administration of a potent NHE1 inhibitor, HOE642, attenuated locomotor and cognitive functional deficits as well as gliosis, oxidative stress, axonal damage, and white matter damage. These findings underscore the role of NHE1 upregulation in r-mTBI-induced oxidative stress, axonal damage, and gliosis, suggesting NHE1 as a promising therapeutic target to alleviate mTBI-induced injuries and restore neurological function.

KV channel-interacting proteins (KChIPs) belong to a family of Ca2+-binding EF-hand proteins that are able to bind to the N-terminus of the KV4 channel α-subunits. As the auxiliary subunit, KChIPs are critically involved in regulating the amplitude and gating properties of KV4 channels by modulating their cell surface trafficking, voltage-dependent activation, inactivation kinetics, and recovery rate from inactivation. IKs, ICa,L, and INa can also be regulated by KChIPs. KChIPs are predominantly expressed in the brain and heart, where they contribute to the maintenance of the excitability of neurons and cardiomyocytes by modulating the KV4 currents. Interestingly, all KChIPs can act as transcription factors to control the expression of genes involved in pain, memory, and circadian regulation. Altered expression of KChIPs has been implicated in the pathogenesis of many diseases, such as arrhythmia, heart failure, Alzheimer's disease, etc. In this review, we summarize the research progress of KChIPs in their structural properties, physiological functions, and pathological roles in disease progression, and provide an overview of the therapeutic potential of KChIPs as pharmacological targets for associated disorders.

CLIPPERS which stand for Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids, is a chronic inflammatory disorder of the central nervous system. The aetiology of CLIPPERS remains unclear, although its pathogenesis shows immune-mediated processes. The diagnosis of CLIPPERS is challenging without a specific biomarker hence, it is important to consider if both the clinical and radiological features are consistent with the diagnosis, or rather any other disease that mimics CLIPPERS. The Authors present a case of a 40-year-old Female patient diagnosed with CLIPPERS syndrome in India. Differential diagnosis, clinical and MRI characteristics of CLIPPERS syndrome, and treatment approaches are discussed.

Imaging-based biomarkers have developed as an effective tool in neurology, providing vital understandings of the structural, functional, and molecular changes associated with neurological disorders. Imaging techniques such as magnetic resonance imaging (MRI), positron emission tomography (PET), single-photon emission computed tomography (SPECT), and computed tomography (CT) have been widely employed to record disease-related alterations in the brain. These techniques provide a wide range of biomarkers, such as functional connectivity patterns, volumetric measurements, molecular imaging agents, and perfusion parameters, enabling the correct identification of neurological disorders. These biomarkers have proven useful in early diagnosis, disease progression tracking, therapy response prediction, and surgical planning. This review emphasizes the various obstacles and limitations that are associated with imaging-based biomarkers. Technical constraints, standardization obstacles, ethical concerns, regulatory challenges, and cost-effectiveness concerns all offer substantial barriers to wider use. It is vital to overcome these challenges if imaging biomarkers are to be successfully integrated into routine clinical practice. Imaging technology advancements like high-resolution imaging, multimodal imaging, and artificial intelligence-based analysis hold immense promise for imaging-based biomarkers in the future. While more study and standardization are needed, their ongoing development and integration into clinical practice have the potential to revolutionize the diagnosis, treatment, and management of neurological disorders, resulting in better patient care and outcomes.

Proteins need to be located in appropriate spatiotemporal contexts to carry out their diverse biological functions. Mislocalized proteins may lead to a broad range of diseases, such as cancer and Alzheimer’s disease. Knowing where a target protein resides within a cell will give insights into tailored drug design for a disease. As the gold validation standard, the conventional wet lab uses fluorescent microscopy imaging, immunoelectron microscopy, and fluorescent biomarker tags for protein subcellular location identification. However, the booming era of proteomics and high-throughput sequencing generates tons of newly discovered proteins, making protein subcel-lular localization by wet-lab experiments a mission impossible. To tackle this concern, in the past decades, artificial intelligence (AI) and machine learning (ML), especially deep learning methods, have made significant progress in this research area. In this article, we review the latest advances in AI-based method development in three typical types of approaches, including sequence-based, knowledge-based, and image-based methods. We also elaborately discuss existing challenges and future directions in AI-based method development in this research field.

Motion related human activity recognition using wearable sensors can potentially enable various useful daily applications. So far, most studies view it as a stand-alone mathematical classification problem without considering the physical nature of human motions. Consequently, they suffer from data dependencies and encounter the dimension disaster problem and the over-fitting issue, and their models are never human-readable. In this study, we start from a deep analysis on natural physical properties of human motions, and then propose a useful feature selection method to quantify each feature's classification contribution capability. On one hand, the "dimension disaster" problem can be avoid to some extent, due to the affined dimension of key features; On the other hand, over-fitting issue can be depressed since the knowledge implied in human motions are nearly invariant, which compensates the possible data inadequacy. The experiment results indicate that the proposed method performs superior to those adopted in related works, such as decision tree, k-NN, SVM, neural networks.

The mechanism of ciprofloxacin action involves interference with transcription and replication of bacterial DNA, which results in elevated oxidative stress, and bacterial cell death. Vorinostat was shown to induce oxidative DNA damage. In the current work, the possibility for interactive effect of vorinotat on ciprofloxacin-induced cytotoxicity against a number of reference bacteria was investigated. Standard bacterial strains were Escherichia coli ATCC 35218, Staphylococcus aureus ATCC29213, Pseudomonas aeruginosa ATCC 9027, Staphylococcus epidermidis ATCC 12228, Acinetobacter baumannii ATCC 17978, Proteus mirabilis ATCC 12459, Klebsiella pneumoniae ATCC 13883, methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43300), and Streptococcus pneumoniae (ATCC 25923). The antibacterial activity of ciprofloxacin with or without pretreatment of bacterial cells by vorinostat was examined using disc diffusion procedure and determination of the minimum inhibitory concentration (MIC) and zones of inhibition of bacterial growth. All tested bacterial strains showed sensitivity to ciprofloxacin. When pretreated with vorinostat, significantly larger zones of inhibition and smaller MIC values were observed in all bacterial strains compared ciprofloxacin alone. As a conclusion, current results showed the possible agonistic properties for vorinostat when it is used together with ciprofloxacin. Future research will be focus on molecular mechanisms possible for such interactive effect.

Delve into the dynamic realms of neuroscience, neurology, and psychiatry with this groundbreaking editorial, unveiling the intricate mechanisms of brain function and dysfunction. Explore the latest advancements in molecular biology, genetics, epigenetics, pharmacology, and neuroimaging that are revolutionizing our understanding of neurological and psychiatric disorders. Uncover the challenges and gaps in translating cutting-edge research into practical clinical applications, aiming to enhance the lives of patients and their families. Discover the pivotal role of neuroplasticity in reshaping the brain's adaptability throughout life, alongside the promising potential of non-invasive brain stimulation techniques like transcranial magnetic stimulation and transcranial direct current stimulation. Embark on a journey of innovation and collaboration as researchers and clinicians strive to bridge the gap between bench and bedside, offering hope for improved diagnosis, prevention, and treatment of complex neurological and psychiatric conditions. Join us in this exploration of transformative ideas and novel interventions that hold the key to a brighter future for individuals and society.

1. Background and Objective: Spontaneous Intracranial Hemorrhage (ICH) is a catastrophic medical condition associated with significant morbidity and mortality. As the accumulation of unbound iron following ICH contributes to secondary brain injury, deferoxamine, an approved chelation drug, has become the center of attention. At the same time, its therapeutic remains a matter of dispute. This double-blinded Randomized Controlled Trial (RCT) aims to investigate the therapeutic potential of deferoxamine in neurological and radiological aspects. 2. Methods and Materials: The study enrolled 42 participants diagnosed with spontaneous ICH and confirmed by CT scan, randomly assigning them to either the deferoxamine treatment group or the placebo control group. While the control group received the routine treatment plus a placebo, the treatment group received routine treatment conjugated with 7.5 mg/kg of deferoxamine per hour intravenously over the first three days. The study compared hematoma and edema volume, GCS score, and mortality rates between the two groups. Our study employed rigorous randomization and blinding procedures to ensure unbiased results. 3. Results: There was a significant (p<0.05) improvement in patients' GCS up until the fourth day, but no significant difference was noted afterward. In addition, the volume of both edema and hematoma was significantly lower in the intervention group, as well as the length of stay, intubation requirement, and mortality. 4. Discussion: Deferoxamine administration can, at least in a short timeframe, improve neurological and radiological parameters.

Background and Objectives: Intramedullary spinal cord tumors (IMSCT) are rare entities. Especially, a location in the upper cervical spine as a highly eloquent region carries the risk of postoperative neurological deficits, such as tetraparesis or respiratory dysfunction. Evidence for respiratory dysfunction is scarce. The aim of this study was to describe the early and late postoperative clinical course of this highly eloquent tumours. Patients and Methods: This is a single-centre retrospective cohort study. We included 35 patients with IMSCT at levels of craniocervical junction to C4 who underwent surgical treatment between January 2008 and December 2022. The authors analysed the patients' preoperative status, tumour- and surgery-specific characteristics, and follow-up functional status. Results: The study cohort included 22 patients with grade II ependymoma (62.9%), 2 low-grade astrocytomas (5.7%), 2 glioblastomas (5.7%), 6 hemangioblastomas (17.1%), 2 metastases (5.7%), and 1 patient with partially intramedullary schwannoma (2.9%). Gross total resection was achieved in 76% of patients. Early dorsal column related symptoms and motor deterioration occurred in 64% and 44% of patients, respectively. At a follow-up of 3.27 ± 3.83 years, 43% and 33% of patients preserved postoperative sensory and motor deterioration, respectively. The median McCormick Scale grade was 2 in the preoperative and late postoperative periods, respectively (p=0.0897, α=0.05). Only two out of 35 patients (5.7%) developed new intermittent respiratory dysfunction, of whom two were transient. There were no surgery-related deaths. Conclusions: The surgery of IMSCT of the upper cervical spine could be performed without major procedure-related risk. Roughly a half of the patients develop new neurological deficit in the immediate postoperative period. However, most of the patients still maintain functional independence. The rate of respiratory insufficiency is low and is strongly influenced by the rapid neurological deterioration in high-grade tumours.

In this paper, a novel microwave catalyst Ni@SiC/CNFs (NSC), C/Ni (NC), and C/SiC (SC) were successfully synthesized by electrostatic spinning method, and proved to degrade methylene blue with high efficiency under microwave irradiation. The results imply that the catalyst Ni@SiC/CNFs with double shell structure gave a 99.99 % removal rate in 90 s for the degradation of methylene blue under microwave irradiation, outperformed the C/Ni and C/SiC and most other reported catalysts in similar studies. On the one hand, the possible mechanism of the methylene blue degradation should be ascribed to that double shell structure increases the polarization source of the material, resulting in excellent microwave absorption properties; and on the other, the in-situ generation of active species OH• and O2 - under microwave radiation and the synergistic coupling effect of metal plasma greatly improved the degradation efficiency of methylene blue. The findings of this study could provide a valuable reference for the green degradation of industrial dye wastewater and its sustainable development process.

Planar catechin (PCat), a natural antioxidant with a fixed 3D catechin structure on a plane, exhibits radical-scavenging activity approximately five times stronger than the conventional catechin. We synthesized a compound, PCat–TrOH, by binding Trolox (TrOH), an α-tocopherol analog, to PCat to enhance its antioxidant effect against oxidative stress, such as lipid peroxidation. TrOH shows radical-scavenging activity about 6.5 times greater than PCat, and PCat–TrOH exhibited a similar level of radical-scavenging activity to TrOH. Additionally, PCat–TrOH demonstrated twice the radical-scavenging activity against reactive oxygen species compared to PCat or TrOH. This compound is also expected to exhibit an excellent antioxidant effect against lipid peroxidation caused by radical chain reactions, through interactions with vitamin C, similar to that in the case of α-tocopherol.

Functional neurological disorders (FND) are relatively frequent disabling conditions. Given their complexity, multidisciplinary rehabilitation is envisaged. Whole-body cryostimulation (WBC) represents a promising adjuvant treatment, mainly because of its anti-inflammatory and exercise-mimicking effects. Here, we propose a novel use of WBC in a wheelchair-ridden 61-year-old woman diagnosed with FND and other comorbidities, who, after several therapeutic and rehabilitation failures, underwent a multidisciplinary rehabilitation program including WBC. The 4-week program included physiotherapy, nutritional intervention, psychological support, and WBC. Questionnaires to assess disease impact, pain level, perceived fatigue and sleep quality were administered. At discharge, improvements in body composition, haematological biomarkers, physical performance, and questionnaire scores were observed. The patient was able to walk with a walker for medium distances, even outdoors. We observed unprecedented improvements, particularly in functional parameters and questionnaire scores. Although we cannot ascertain to which extent WBC per se contributed to the improvements measured, subjective reporting and our clinical observation were that WBC, the only intervention not previously experienced by the patient, acted as a booster for the rehabilitation interventions. Further research will be necessary to rule out any possible placebo effect and to assess the effects of WBC on FND.

The gut-brain axis (GBA) represents a complex, bidirectional communication network that intri-cately connects the gastrointestinal tract with the central nervous system (CNS). Understanding and intervening in this axis opens a pathway for therapeutic advancements. In light of this, the current review assesses the effectiveness of neuromodulation techniques in treating neurological and gastrointestinal disorders by modulating the GBA, involving key elements such as gut micro-biota, neurotrophic factors, and proinflammatory cytokines. Through a comprehensive literature review encompassing PubMed, Google Scholar, Web of Science, and the Cochrane Library, and analyzing 182 relevant articles, this research highlights how neuromodulation can positively impact the management of functional gastrointestinal disorders (FGIDs), chronic pain, inflammation, and a range of GI disorders like Crohn's disease and ulcerative colitis. Despite existing challenges, the ability of neuromodulation to adjust disrupted neural pathways, alleviate pain, and mitigate in-flammation is significant in improving the quality of life for patients, thereby offering exciting prospects for future advancements in patient care.

Immersive virtual reality has the potential to motivate and challenge patients that need and want to relearn movements in the process of (neuro-)rehabilitation. The aims of this study were to evaluate the feasibility and users’ acceptance of an innovative immersive virtual reality system (head-mounted display) used in combination with robot assisted gait training in subjects suffering from neurological diseases. Fifteen participants tested a single session of immersive virtual reality by means of head-mounted display during a Lokomat gait session. Training parameters and safety indicators were collected and the acceptance was investigated among the participants and the therapists. The results suggest that the immersive virtual reality system is feasible with respect to safety and tolerance. Furthermore, the very positive overall acceptance of the system suggests that it has potential to be included in a robot assisted gait training session by means of Lokomat. Taken together, this study demonstrates the feasibility and acceptance of an innovative immersive virtual reality system in combination with a robot assisted gait training in subjects suffering from stroke and spinal cord injury, as well as their therapists.

Essential oils (EOs) have been gaining popularity in the past decades among researchers due to their potential to replace conventional chemicals used in the fight against pests, pathogenic and spoilage microbes and oxidation processes. EOs are complex mixtures with many chemical components the content of which depends on many factors – not just the plant genus, species or subspecies, but also chemotype, locality and climatic conditions, phase of vegetation, method of extraction and others. Due to this fact, there’s still much to study, with antimicrobial effect being one of the key properties of EOs. There are many methods that have been frequently engaged by researchers for in vitro evaluation; however, although the research has been going on for decades, an internationally accepted standard is still missing. Most of methods are based on time-proven standards used for testing of antibiotics. Due to the specific properties of EOs and their components, such as volatility and hydrophobicity, many modifications of these standard procedures have been adopted. The aim of this review is to describe the most common methods and their modifications for testing of antimicrobial properties of EOs and to point out the most controversial variables which can potentially affect results of the assays.

Resveratrol (RSV), a naturally occurring phytoalexin, is the most important stilbenoid synthesized by plants, as a defense mechanism, in response to microbial aggression, toxins or ultraviolet radiation. RSV came to the attention of researchers both as a potential chemopreventive agent and a possible explanation for the low incidence of cardiovascular disease (CVD) in French people with a high-fat diet. RSV is mainly administered as a food supplement, its properties being evaluated in vitro or in vivo, on various experimental models. RSV modulates signaling pathways that limit the spread of tumor cells, protects nerve cells from damage, is useful in the prevention of diabetes, and generally acts as an anti-aging natural compound. It was highlighted that RSV could ameliorate the consequences of an unhealthy lifestyle caused by an exaggerated caloric intake. This paper reviews the evidence supporting the beneficial effect of RSV for various pathological conditions, e.g., neoplastic diseases, neurodegeneration, metabolic syndrome, diabetes, obesity, CVDs, immune diseases, bacterial, viral, and fungal infections. The study also focused on the chromatographic analysis of trans-RSV (tRSV) in Romanian wine samples, providing a comprehensive overview of tRSV content across different types of wine.

Volcanic activity essentially consists of the transfer of heat from the Earth’ interior to the surface. The precise signature of this heat transfer relates directly to the processes underway at and within a particular volcano and this can be observed, at a safe distance, remotely, using infrared sensors that are present on Earth-orbiting satellites. For over 50 years, scientists have perfected this art using sensors intended for other purposes, and they are now in a position to determine the particular sort of activity that characterizes different volcanoes. This review will describe the theoretical basis of the discipline and then discuss the sensors available for the task and the history of their use. Challenges and opportunities for future development in the discipline are then discussed.

The medicinal herb Centaurium erythraea is well-known for its natural ability to treat digestive issues like dyspepsia and liver insufficiency by promoting the secretions of the liver and esophagus. This study aimed to analyze the effectiveness of Centaurium erythraea extracts in treating diabetes. Decoction and Soxhlet procedures were used to examine the extracts, with water serving as the solvent. The extracts were tested for antioxidant capacity, antimicrobial effects, and inhibitory effects on alpha-amylase activity. In comparison to the aqueous extract, the decocted extract had higher levels of polyphenols, total tannins, and anthocyanins, as well as more effective antioxidant capacities. Due to its reduction of alpha-amylase activity and enteric absorption of glucose, Centaurium erythraea has also shown considerable anti-hyperglycemic action.

Pharmacogenetics and DNA methylation influence therapeutic outcomes and provide insights into potential therapeutic targets for brain-related disorders. To understand the effect of genetic polymorphisms on drug response and disease risk, we analyzed the relationship between global DNA methylation, drug-metabolizing enzymes, transport genes, and pathogenic gene phenotypes in serum samples from two groups of patients: Group A, which showed increased 5-methylcytosine (5mC) levels during clinical follow-up, and Group B, which exhibited no discernible change in 5mC levels. We identified specific SNPs in several metabolizing genes, including CYP1A2, CYP2C9, CYP4F2, GSTP1, and NAT2 that were associated with differential drug responses. Specific SNPs in CYP had a significant impact on enzyme activity, leading to changes in phenotypic distribution between the two patient groups. Group B, which contained a lower frequency of normal metabolizers and a higher frequency of ultra-rapid metabolizers compared to patients in Group A, did not show an improvement in 5mC levels during follow-up. Furthermore, there were significant differences in phenotype distribution between patient Groups A and B for several SNPs associated with transporter genes (ABCB1, ABCC2, SLC2A9, SLC39A8, and SLCO1B1) and pathogenic genes (APOE, NBEA, and PTGS2). These findings appear to suggest that the interplay between pharmacogenomics and DNA methylation has important implications for improving treatment outcomes in patients with brain-related disorders.

Background: The incidence of spinal metastatic disease has risen with improved cancer survivorship. Separation surgery, the current standard surgical treatment, does not fully address spinal deformity. Advances in operative management warrant reevaluating maximal tumor resection and anterior column reconstruction with corpectomy. Methods: An IRB-approved retrospective single-center review of 63 patients was performed. Demographics, tumor characteristics, clinical and radiographic data, treatments, and neurological and survival outcomes were analyzed. Results: The mean age at presentation was 63.5 ± 9.6 years (range, 37-84 years) and 28 patients (44.4%) were female. Functional outcomes, measured by KPS, RAND-36 survey scores and Oswestry Disability Index all improved postoperatively (pre- vs postop: 70 to 80 (p=0.0056), 26.5 to 46.4 (p=0.0081), and 28.9 to 16.9 (p=0.0613), respectively). Spinal alignment also improved, with Cobb angle measurements showing a reduction in spinal kyphosis from -5 to 0 (p=0.021). Nine patients (14.5%) had non-fatal postoperative complications. The median OS for this cohort was 14.4 months (range, 0.6-145.0 months) with median follow-up time of 15.5 months. Conclusion: In oligometastatic spinal disease patients with good functional status, corpectomy for decompression of neural elements, deformity correction, and spinal stabilization is associated with improvements in pain and functional outcomes without overwhelming morbidity.

Lipids have not traditionally been considered likely candidates for catalyzing reactions in biological systems. However, there is significant evidence that aggregates of amphiphilic compounds are capable of catalyzing reactions in synthetic organic chemistry. Here we demonstrate the potential for the hydrophobic region of a lipid bilayer to provide an environment suitable for catalysis by means of a lipozyme, or lipid aggregate capable of speeding up a chemical reaction. By bringing organic molecules into the non-polar or hydrophobic region of a lipid bilayer, reactions can be catalyzed by collections of small, nonpolar or amphiphilic molecules. We demonstrate this concept by the ester hydrolysis of calcein-AM to produce a fluorescent product, which is a widely used assay for esterase activity in cells. The reaction was first carried out in a two phase octanol-water system with the organic phase containing the cationic amphiphiles cetyltrimethylammonium bromide (CTAB) or octadecylamine. The octanol was then replaced with DOPC added to the water in the form of vesicles, where the reaction was also found to be carried out. The reaction was monitored using quantitative fluorescence which revealed catalytic turnover numbers on a scale of 10−4s−1 for each system, which is comparable to some slow enzymes. The reaction product was characterized by 1H-NMR measurements which were consistent with ester hydrolysis. The implications of thinking about lipid aggregates as catalytic entities are discussed in the context of biochemistry, pharmacology and synthetic biology.

: Background: Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. Methods: Twenty-five healthy adults (25.8±3.3 years, 15 female) were analyzed in a randomized, controlled cross-over study. Each intervention began with a 30 min resting phase under normoxia (NOR), followed by a 90 min continuation of NOR or NH (peripheral oxygen saturation [SpO₂] 85-80%). Serum and plasma samples were collected every 15 min. Heart rate and SpO₂ were continuously measured. Before and after each exposure, cognitive tests were performed and after 24 h another follow-up blood sample was taken. Results: NH decreased SpO₂ (p<.001, η_p²=.747) and increased heart rate (p=.006, η_p²=.116) significantly. The 30-min resting phase under NOR led to a significant BDNF reduction in serum (p <.001, η_p²=.581) and plasma (p <.001, η_p²=.362). Continuation of NOR further significantly reduced BDNF after another 45 min (p=.018) in serum and after 30 min (p=.040) and 90 min (p=.005) in plasma. There was no significant BDNF decline under NH. 24 h Follow-up examination showed a significant decline of serum BDNF, both after NH and NOR. Conclusion: Our results show that NH has the potential to counteract physical inactivity-induced BDNF decline. Therefore, our study emphasizes the need for a physically active lifestyle and its positive effects on BDNF. This study also demonstrates the need for a standardized protocol for future studies to determine BDNF in serum and plasma.

The BL Lacertae (BL Lac) object OJ 287 underwent an intense X-ray activity phase, exhibiting its brightest recorded X-ray flare in 2016-2017, characterized by much softer X-ray spectra and, concurrently, its first-ever recorded very-high-energy (VHE) emission (100--560 GeV), reported by the VERITAS observatory. Broadband spectral energy distribution reveals a new jet emission component similar to high-synchrotron-peaked BL Lac objects, thereby implying the soft X-ray spectrum for the synchrotron emission. Using the advantage of simultaneous X-ray and VHE spectral information, as well as the source being a low-synchrotron-peaked BL Lac object, we systematically explored the extragalactic background light (EBL) spectrum by demanding that the VHE spectrum cannot be harder than the X-ray spectrum. We used three different phenomenological forms of the EBL spectral shape (power-law, parabola, and polynomial) motivated by current constraints on the EBL with the Bayesian Monte Carlo approach to infer the credible EBL range. Our study favors an almost flat power-law spectral shape and is consistent with previous studies. The other spectral forms capable of capturing curvature though result in a better statistics value; the improvement is statistically insignificant given the additional parameters.

Background/Objectives: Endometriosis represents substantial direct and indirect healthcare costs impacted by absent accurate, non-invasive uniformly diagnostic tools. We endeavored to demonstrate gastrointestinal myoelectrical activity (GIMA) biomarkers unique to endometriosis allow noninvasive, uniformly accurate diagnosis or exclusion of endometriosis. Methods: Prospective open-label comparative study of 154 patients, age &gt;18, with or without diagnosed endometriosis. Population included 62 non-endometriosis controls (Cohort 1), 43 subjects with surgically histologically-confirmed endometriosis (Cohort 2), and 49 subjects with abdominal pain and negative imaging (Cohort 3). Electroviscerography (EVG) recorded GIMA biomarkers from three abdominal electrodes before and 30-minutes post water-load protocol. Cohort 2 had postoperative EVG and Cohort 3 had preoperative EVG. Calculated specificity, sensitivity, NPV, PPV and predictive probability or C-Statistic used univariate, multivariate, linear and logistical regression analyses of the area under the curve (AUC) at all frequency and time points, including age and pain covariants. Results: Non-endometriosis cohort differed significantly from endometriosis cohorts (p&lt;0.001) for median (IQR), and AUC percent frequency distribution of power at baseline, 10-minute, 20-minute, and 30-minute post water-load at all frequency ranges 15-20cpm, 30-40cpm and 40-50cpm. Endometriosis cohorts were statistically similar (p&gt;0.05). GIMA biomarker threshold scoring demonstrated 95%/91% sensitivity and PPV, 96%/95% specificity and NPV and C-statistic of &gt;99%/98% respectively for age subsets. GIMA biomarkers in Cohort 3 predicted 47/49 subjects positive and 2/49 negative for endometriosis, confirmed surgically. Hormonal therapy, surgical stage, nor pain score affected diagnostic accuracy. Conclusions: Non-invasive electroviscerography with GIMA biomarker detection distinguished participants with and without endometriosis based upon endometriosis specific GIMA biomarkers threshold scoring.

Plants and plant-derived food products have been used for medicinal purposes since the ancient. Medicinal Plant-based functional foods or plant-based dietary compounds are a re-emerged interest for their therapeutic benefits and nutritive supports which has implicated in healthcare systems across the world. Neurological disorders are one of the greatest threats to public health and according to the World Health Organization, about 100 million people are affected globally by several neurological and mental ailments. In a traditional medication system, medicinal plants have been applied as both neuro-therapeutic purposes and micro-macro nutrients provider for the wellbeing of psychological states e.g. anti-depressant, anti-anxiety, anti-convulsions, anti-dementia, anti-psychotic, etc. Herein, it is a topic of great interest to present a conceptual aspect by reviewing relevant scientific literature about the plant-based functional foods or bioactive phytochemicals for the prevention and treatment of mental and neurological disorders. From the literature assessment, we have found that nutritional neuroscience is becoming an advanced research discipline and there has been a growing pile of evidence concerning the therapeutic use of plant-based functional foods and/or plant-derived food compounds for the management of neurologic health, evolving with promising impact over the time.

It is widely known that vitamin D receptors have been found in neurons and glial cells and their highest expression is in the hippocampus, hypothalamus, thalamus and subcortical grey nuclei, and substantia nigra. The vitamin D helps the regulation of neurotrophin, neural differentiation and maturation, through the control operation of growing factors synthesis (ie NGF and GDNF), the trafficking of the septo-hyppocampal pathway, and the control of the synthesis process of different neuromodulators (such as Ach, DA, and GABA). Based on these assumptions, we have written this review in order to summarize the potential role of vitamin D in neurological pathologies. The work could be titanic, and might result very fuzzy and even incoherent, if we would not have conjectured to taper our first intentions and devoted our interests towards three mainstreams: demyelinating pathologies, vascular syndromes and neurodegeneration. Due to the lack of effective therapeutic options, a part from the disease modifying strategies, the role of different risk factors should be investigated in neurology, as far as their correction may lead to the improvement of the cerebral conditions. We have explored the relationships between the gene-environmental influence and long term vitamin D deficiency, as a risk factor for the development of different types of neurological disorders, along with the role and the rationale of therapeutic trials with vitamin D implementation.

Background: Despite the tremendous effort in hamstring injury prevention, injury rates in soccer remain elevated. Hypothesis: Hamstring and hip/pelvic isometric strength imbalances may increase the likelihood of hamstring strain injury (HSI) occurrence amongst soccer players.Study design: Case-control study.Methods: In 120 male soccer players (mean age: 20.0 +/- 6.96 years) pre-season maximum isometric strength of the hip adductors, abductors, flexors, and knee flexors were measured, and strength ratios were calculated. Previous injury and anthropometric data were registered. Injury data were collected following the FIFA/UEFA consensus. A multivariate and Machine learning-based Logistic Regression model was employed to estimate the likelihood of players sustaining a hamstring injury.Results: 21 players sustained 32 hamstring injuries. Players with higher abduction strength in the dominant leg had an 18.5% lower risk of sustaining a hamstring injury (OR = 0.818, CI 95% = [(0.695-0.964]). No other significant contributor variables were found to be significant predictors of hamstring injury in the player group (p> 0.05).Conclusion: Isometric strength of the abductor muscles in the dominant limb had a significant association with hamstring injury.Clinical relevance: Our findings indicate the utilization of hip strength measurements as an integral component of the pre-season screening assessment, thereby affirming prior research on the correlation between lumbo-pelvic stability and incidence of hamstring injuries. Consequently, clinicians should contemplate incorporating hip strengthening exercises into regular training sessions, rehabilitation programs, and injury prevention protocols especially indicated when lower hip strength levels are observed.

This research introduces a hybrid feature extraction approach that combines Linear Discriminant Analysis (LDA) and Multilayer Perceptron (MLP) methods to address the challenges of reducing feature vector dimensionality and accurately classifying smartphone-based human activities. Moreover, to refine activity classification accuracy, Support Vector Machine (SVM) optimization with Stochastic Gradient Descent (SGD) is employed. LDA, a statistical tool, is leveraged to derive a new feature space for data projection, enhancing class separation and test feature label prediction. The proposed approach, named LMSS, was evaluated using the UCI-HAR dataset and compared with state-of-the-art models. The results demonstrate that the proposed approach outperformed the best-performing method over this dataset. It achieved an accuracy rate of 99.52%, precision of 99.55%, recall of 99.53%, and an F1-score of 99.54%, highlighting the effectiveness of the proposed method in accurately classifying the data.

MicroRNAs (miRNA) exert regulatory actions via base-pairing with their binding sites on target mRNAs. Cooperative-binding, i.e., synergism, among binding sites on a mRNA is biochemically well-characterized. We studied whether this synergism is reflected in global relationship between miRNA-mediated regulatory activity and miRNA-binding-site count on the target mRNAs, i.e., leading to a non-linear relationship between the two. Recently, using our own and public datasets, we have enquired into miRNA regulatory actions: first, we analyzed the power-law distribution pattern of miRNA binding sites; second, strikingly, mRNAs for core miRNA regulatory apparatus proteins have extra-ordinarily high binding site counts, forming self-feedback-control loops; third, we revealed that tumor suppressor mRNAs generally have more sites than oncogene mRNAs; and fourth, we characterized enrichment of miRNA target mRNAs in translationally less-active polysomes relative to more-active polysomes. In these four studies, obvious correlation was observed qualitatively between the extent to which a mRNA is miRNA-regulated and its binding sites count. This paper summarizes the used datasets. We also re-analyzed the correlation by comparative linear and non-linear regression analyses. The results support a non-linear, instead of linear, relationship between the two parameters, conceivably a transcriptome-level reflection of cooperative-binding/synergism among miRNA binding sites on a target mRNA.

This paper presents a particular tunneling method or new Austrian tunneling method (NATM) which plays an important role in reducing the subsidence of the Earth surface and the damage to the structures in urban areas. It has a wide range of applications in shallow tunneling projects all over the world. In this study, numerical modeling of third-line Metro tunnel in Tehran is under discussion which is designed and stabilized by NATM. The foregoing tunnel is excavated manually with a one-meter advancing step. In this project, the constructors used a lattice girder and sprayed concrete with 31 cm thickness as the initial lining. A suitable numerical software for this modeling is Plaxis 3D tunnel, which allows performing high-resolution finite element modeling (FEM) of the studied object. The performance of this method is investigated and compared with other NATM methods. As a result of numerical modeling, we give a value of 30.01 mm earth subsidence in the most damaged area of the settlement, in comparing with that of earth surface monitoring, which confirmed it with a dramatically low difference. Moreover, this tunnel was drilled and excavated with various methods, among which the less settlement has obtained by the proposed method. The results are promising to continue the tunneling with this method to expand the subway line in the city.

This paper presents an on-device semi-supervised human activity detection system that can learn and predict human activity patterns in real time. The proposed semi-supervised learning (SSL) framework uses sparsely labelled user activity events acquired from Inertial Measurement Unit (IMU) sensors installed as wearable device. The objective is to learn classification of multiple classes of human activities in real-time. The proposed cluster-based learning model in this approach is trained with data from the same target user, thus preserving data privacy while providing personalized activity detection services. Two different cluster labelling strategies, namely, population-based, and distance-based, are employed to achieve the desired classification performance. A comparative study of these strategies has been presented in terms of classifiability and classification accuracies. The proposed system is shown to be computationally efficient, which is relevant in the context of limited computing resources on typical wearable devices. The trade-off between classification accuracy and computation complexity is analyzed for different algorithmic hyper-parameters and other system parameters. Extensive experimentation and simulation study have been conducted on a multi-user human activity data from the public do-main in order to validate the proposed learning paradigm.

We have previously shown that the transmembrane protein ODZ1 promotes cytoskeletal remodelling of glioblastoma (GBM) cells and invasion of the surrounding parenchyma through activation of a RhoA-ROCK pathway. We also described that GBM cells can control the expression of ODZ1 through transcriptional mechanisms triggered by binding of IL-6 to its receptor and a hypoxic environment. Epidermal growth factor (EGF) plays a key role in the invasive capacity of GBM. However, the molecular mechanisms that enable tumor cells to acquire the morphological changes to migrate out from the tumor core have not been fully characterized. Here we show that EGF is able to induce the expression of ODZ1 in primary GBM cells. We analysed the levels of EGF receptor (EGFR) in 20 GBM primary cell lines and found expression in 19 of them by flow cytometry. We selected two cell lines that do or do not express EGFR and found that EGFR-expressing cells responded to EGF ligand by increasing ODZ1 at the mRNA and protein level. Moreover, blockade of EGF-EGFR binding by Cetuximab, inhibition of the p38 MAPK pathway or siRNA-mediated knockdown of MAPK11 (p38 MAPK) reduced the induction of ODZ1 in response to EGF. Overall, we show that EGF may activate an EGFR-mediated signalling pathway through p38 MAPK, to upregulate the invasion factor ODZ1, which may initiate morphological changes for tumor cells to invade the surrounding parenchyma. These data identify a new candidate of the EGF-EGFR pathway for novel therapeutic approaches.

Pain is a multifaceted multisystem disorder that adversely affects neuro-psychological processes. This study compares the effectiveness of central-stimulation (tDCS) and peripheral-stimulation (TENS) in pain-inhibition during a cognitive-task in healthy volunteers and to observe potential neuro-cognitive improvements. Healthy eighty volunteers went through a complete experimental protocol comprising pain-induction (CPT), administration of tDCS/TENS, EEG-data acquisition, and cognitive assessments. The protocol for this study is categorized into 04-groups: G1(Control), G2(TENS), G3(Anodal-tDCS), and G4(Cathodal-tDCS). Paired t-tests (p

Magnetic resonance (MR) image acquisitions are usually time-consuming, limiting utilization in neuroimaging. For multiple sclerosis (MS) patients, MR imaging plays a major role in drug therapy decision-making. The purpose of this study was to evaluate whether an ultrafast, T2-weighted (T2w), deep-learning-enhanced (DL), echo-planar-imaging-based (EPI) fluid-attenuated inversion recovery (FLAIR) sequence (FLAIRUF) that has been targeting neurological emergencies so far might even be an option to detect MS lesions of the brain compared to conventional FLAIR sequences. Therefore, 17 MS patients were enrolled prospectively in this exploratory study. Standard MR protocols and ultrafast acquisitions were conducted at 3 tesla (T), including three-dimensional (3D)-FLAIR, turbo/fast spin echo (TSE)-FLAIR, and FLAIRUF. Inflammatory lesions were grouped by size and location. Lesion conspicuity and image quality were rated on an ordinal five-point Likert scale, and lesion detection rates were calculated. Statistical analyses were performed to compare results. Altogether, 568 different lesions were found. Data indicated no significant differences in lesion detection (sensitivity and positive predictive value [PPV]) between FLAIRUF and axially reconstructed 3D-FLAIR (lesion size ≥ 3 mm × ≥ 2 mm) and no differences in sensitivity between FLAIRUF and TSE-FLAIR (lesion size ≥ 3 mm total). Lesion conspicuity in FLAIRUF was similar in all brain regions except for superior conspicuity in the occipital lobe and inferior conspicuity in central brain regions. Further findings include location-dependent limitations of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) as well as artifacts such as spatial distortions in FLAIRUF. In conclusion, FLAIRUF could potentially be an expedient alternative to conventional methods for brain imaging in MS patients since the acquisition can be performed in a fraction of time while maintaining good image quality.

Recent advancements in cognitive neuroscience, particularly in Electroencephalogram (EEG) signal processing, image generation, and brain-computer interfaces (BCI), have opened up new avenues for research. This study introduces a novel framework, Bridging Artificial Intelligence and Neurological Signals (BRAINS), which leverages the power of AI to extract meaningful information from EEG signals and generate images. The BRAINS framework addresses the limitations of traditional EEG analysis techniques, which struggle with nonstationary signals, spectral estimation, and noise sensitivity. Instead, BRAINS employs Long Short-Term Memory (LSTM) networks and contrastive learning, which effectively handle time-series EEG data and recognize intrinsic connections and patterns. The study utilizes the MNIST dataset of handwritten digits as stimuli in EEG experiments, allowing for diverse yet controlled stimuli. The data collected is then processed through an LSTM-based network employing contrastive learning and extracting complex features from EEG data. These features are fed into an image generator model, producing images as close to the original stimuli as possible. This study demonstrates the potential of integrating AI and EEG technology, offering promising implications for the future of brain-computer interfaces.

Revealing the underlying pathomechanisms of neurological and psychiatric disorders, searching for new biomarkers, and developing novel therapeutics all require translational research. In vivo and in vitro disease models have been instrumental in casting light on complex polygenic, multifactorial, and heterogeneous disease mechanisms. In the most recent years, advanced preclinical models have revealed the intriguing interaction of sex/gender and aging with the pathogenesis and clinical manifestations of psychiatric and neurological diseases. However, despite these advancements, there is still a great deal of work to be done to fully comprehend the underlying mechanisms of these diseases and to develop treatments that can significantly improve the lives of those who suffer from them. The current challenge in the field of neurological and psychiatric diseases is to develop disease-modifying, effective treatments for these complex and long-lasting debilitating conditions with a high burden of disease.The first edition of the research topic ‘Emerging Translational Research in Neurological and Psychiatric Diseases: From In Vitro to In Vivo Models’ reinforces translational research playing a critical role in bridging the gap between basic research and clinical applications. Also, it provides a platform for researchers to share their findings and advancements in translational research in this field. This new collection gathers 25 papers offering insights into the latest advancements in translational research and potential new avenues for treatments. These papers cover various topics, including the development of new preclinical models, the use of in vitro and in vivo methods, and the application of qualitative and quantitative research methods.

A large body of evidence, replicated in many mouse models of Alzheimer Disease (AD), demonstrated the therapeutic efficacy of oral rapamycin. Administration of m-TOR inhibitors (mTOR-Is), early after the clinical onset, greatly diminished cognitive impairment, amyloid angiopathy, intracellular beta Amyloid and neurofibrillary tangles load. The daily intake of rapamycin has always been 2.24g/Kg/24h. In humans the maximal tolerated oral dose is a few milligrams/day, and at this dosage patients are severely immunosuppressed. Thanks to rapalogs’ scarce CNS-related side effects, we administered intracerebroventricularly (ICV) high doses of the mTOR-I everolimus in a mouse model of AD (3xTg-AD) without significant systemic effects. The instability of the liquid formulation at body temperature (BT) made the treatment very short. Nevertheless, the efficacy of the treatment was high and much longer lasting than expected. In order to set up a thermostable, translational liquid formulation of mTOR-Is, we loaded everolimus in distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000) micelles by the thin layer method. The formulation we obtained maintained over 95% of activity after 14 days at BT. We can envision short, potentially periodic ICV treatments in AD patients which replicate results obtained on animal models. The treatment could benefit also Tuberous Sclerosis and Multiple Sclerosis patients.

Pericytes are increasingly recognized as being important in the control of blood-brain barrier permeability and vascular flow. Research on this important cell type has been hindered by widespread confusion regarding the phenotypic identity and nomenclature of pericytes and other perivascular cell types. In addition, pericyte heterogeneity and mouse-human species differences have contributed to confusion. Herein we summarize our present knowledge on the identification of pericytes and pericyte subsets in humans, primarily focusing on recent findings in humans and nonhuman primates. Precise identification and definition of pericytes and pericyte subsets in humans may help us to better understand pericyte biology and develop new therapeutic approaches specifically targeting disease-associated pericyte subsets.

Background: Strength assessment is one of the main fields in sports performance, physical rehabilitation, physical activity and health. Purpose: To compare maximal voluntary isometric contractions (MVIC) and paired voluntary isometric contractions (VIC) of knee extensors between an isokinetic dynamometer (BIODEX) and a portable and lightweight device (DINABANG). Methods: From 19 volunteers (age: 28.7±7 y; body mass: 72±10 kg and height: 173±7 cm) we obtained 114 paired MVIC measures and, from the force-time curves of these repetitions, 22507 paired VIC measures of knee extensors. Results: We observed “excellent” repeatability for MVIC (ICC:1.00; p&lt;0.001) between BIODEX (247±79.5 Nm) and DINABANG (247±74.8 Nm), with “trivial” effect (mean difference: 0.12 Nm (0.02%); 95%CI: -0.13 to 0.23 Nm; p=0.606; d=0.048). Bland-Altman plots revealed high accuracy for MVIC (bias: 0.12 Nm) and consistent distribution (precision) inside the limits of agreement (-4.81 to 5.06 Nm) and respective 95%CI. “Excellent” repeatability was also observed for VIC (ICC:1.00; p&lt;0.001) between BIODEX (219±84.1 Nm) and DINABANG (218±84.0 Nm), with “trivial” effect (0.24 Nm (0.11%); 0.08 to 0.11 Nm; p&lt;0.001; d=0.100). Bland-Altman plots revealed high accuracy for VIC (bias: 0.24 Nm) and consistent distribution (precision) inside the limits of agreement (-4.5 to 4.9 Nm) and respective 95%CI. Conclusion: DINABANG is accurate, precise and reliable for torque measurement.

Postbiotic is a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host. Different bacterial strain and preparation method result in different functions. Herein, a postbiotic preparation named Postbiotic-P by intercepting 1-5 KD of the cell-free supernatants of L. caseiparacasei P6 fermentation broth was prepared, and its multifunctional activities were evaluated. The results showed that Postbiotic-P exerted good antihemolytic (10%-50% Postbiotic-P resulted in 4.9%-48.1% antihemolytic rate), anti-inflammatory (8% to 40% Postbiotic-P is comparable to 259.1-645.4 μg/mL of diclofenac sodium equivalents), antioxidant [reducing power (1.25%-12.5% Postbiotic-P resulted in the increase of OD700 from 0.279-2.322), DPPH free radical scavenging activity (2.5%-50% Postbiotic-P resulted in 38.9%-92.4% free radical scavenging rate), and hydroxyl radical scavenging activity (0.5%-4% Postbiotic-P resulted in 4.66%-10.38% hydroxyl radical scavenging rate)], and antimicrobial activities (against 2 Gram-positive, 8 Gram-negative and 1 fungus). Furthermore, it was proved that Postbiotic-P could significantly inhibit the increase of the peroxide value and the malondialdehyde content in cookies, indicating the application potential of Postbiotic-P in food preservation. Taken together, Postbiotic-P has good application potential for the development of health care products and functional foods. However, further studies are needed to determine their precise mechanism of action, to clarify the active components responsible for the function, and to validate the biological activities in animal models or clinical trials.

Acute lung injury (ALI) is characterized by inflammation of the lung tissue and oxidative injury caused by excessive accumulation of reactive oxygen species. Studies have suggested that anti-inflammatory or antioxidant agents could be used for the treatment of ALI with a good outcome. Therefore, our study aimed to test whether the mycelium extract of Sanghuangporus sanghuang (SS-1), believed to exhibit antioxidant and anti-inflammatory properties, could be used against the excessive inflammatory response associated with LPS-induced ALI in mice and to investigate its possible mechanism of action. The experimental results showed that the administration of SS-1 could inhibit LPS-induced inflammation. SS-1 could reduce the number of inflammatory cells, inhibit MPO activity, regulate the TLR4/PI3K/Akt/mTOR pathway and the signal transduction of NF-κB and MAPK pathways in the lung tissue, and inhibit HNGB1 activity in BALF. In addition, SS-1 could affect the synthesis of antioxidant enzymes HO-1 and Trx-1 in the lung tissue and regulate signal transduction in the KAP1/Nrf2/Keap1 pathway. Histological results showed that administration of SS-1 prior to induction could inhibit the large-scale LPS-induced neutrophil infiltration of the lung tissue. Therefore, based on all experimental results, we propose that SS-1 exhibits a protective effect against LPS-induced (ALI) in mice. The mycelium of S. sanghuang can potentially be used for the treatment or prevention of inflammation-related diseases

Since the discovery of transposable elements (TEs) in Maize in the 1940s by Barbara McClintock [1] transposable elements have been described as junk, as selfish elements with no benefit to the host, and more recently as major determinants of genome structure and genome evolution. TEs are DNA sequences that are capable of moving to new sites in the genome and make additional copies while doing so. To limit the propagation of TEs, host silencing mechanisms are directed at transposon-encoded genes that are required for mobilization. The mutagenic properties of TEs, the potential of TEs to form new genes and affect gene expression, together with the host silencing mechanisms shape eukaryotic genomes and drive genome evolution. While TEs constitute more than half of the genome in many higher eukaryotes, transposable elements in the nematode C. ele-gans form a relatively small proportion of genome, about 15% [2]. Genetic studies of transposon silencing and the discovery of RNAi in C. elegans, propelled C. elegans to the forefront of studies of RNA-based mechanisms that silence TEs. Here, I will review the transposable elements that are present and active in the C. elegans genome, and the host defense mechanisms that silence these elements.

Molecular hybridization is a widely used strategy in drug discovery and development processes that consists in the combination of two bioactive compounds toward a novel entity. In the current study, two libraries of hybrid derivatives coming from the linkage of sesquiterpene counterparts dihydroartemisinin and artesunic acid with a series of monoterpenes were synthesized and evaluated by cell viability assay on primary and metastatic melanoma cell lines. Almost all the obtained compounds showed micromolar antimelanoma activity and selectivity toward the metastatic form of this cancer. Four hybrid derivatives containing perillyl alcohol, citronellol, and nerol as monoterpene counterpart, emerged as the best compounds of the series, with nerol being active in combination with both sesquiterpenes, dihydroartemisinin and artesunic acid. Preliminary studies on the mechanism of action have shown the dependence of the pharmacological activity of newly synthesized hybrids on the formation of carbon- and oxygen-centered radical species. This study demonstrated the positive modulation of the pharmacodynamic effect of artemisinin semisynthetic derivatives dihydroartemisinin and artesunic acid due to the hybridization with monoterpene counterparts.

The recently emerged coronavirus named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS- CoV-2) is the newest threat to human health. It has already infected more than half a million people worldwide, leading to a lot of deaths. Although it causes mild flu-like disease in most patients, lethality may increase to more than 20% in elderly subjects, especially those with comorbidities, like hypertension, diabetes or lung and cardiac disease, and the mechanisms are still elusive. Common symptoms at the onset of illness are fever, cough, myalgia or fatigue, headache, and diarrhea or constipation. Interestingly, respiratory viruses have also placed themselves as relevant agents for CNS pathologies. Here we discuss several CNS related features, referred by several patients, especially at the beginning of the disease. Thus, we also discuss the possibility by which SARS-CoV-2 may affect the olfactive system of patients, either directly or indirectly.

Ti and its alloys are the most commonly used materials for biomedical applications. However, bacterial infection after implant placement is still one of the significant rising complications. Therefore, the application of the antimicrobial agents into implant surfaces to prevent implant-associated infection has attracted lots of attention. Scientific papers have shown that inorganic antibacterial metal element (e.g. Ag, Cu, Zn) can be introduced to implant surfaces with the addition of metal nanoparticles or metallic compounds into electrolyte via micro-arc oxidation (MAO) technology. In this review, the effects of the composition and concentration of electrolyte and process parameters (e.g. voltage, current density, oxidation time) on morphological characteristics (e.g. surface morphology, bonding strength), antibacterial ability and biocompatibility of MAO antimicrobial coating were discussed in detail. Anti-infection and osseo-integration can be simultaneously accomplished with the selection of the proper antibacterial elements and operating parameters. Besides, MAO assisted by magnetron sputtering (MS) to endow Ti-based implant materials with superior antibacterial ability and biocompatibility was also discussed. Finally, the development trend of MAO technology in the future was forecasted.

Obesity is a highly prevalent chronic disease characterized by excessive weight gain and fat accumulation. There is growing evidence that Lactiplantibacillus plantarum strains with bile salt hydrolase (BSH) activity are effective in preventing and alleviating obesity. However, few of them has confirmed the anti-obesity effect of BSH by gene deletion. In this study, 23 BSH-positive Lp. plantarum strains were screened by bile salt precipitation halo assay. Among these strains, Lp. plantarum Lp20 showed the highest BSH activity with a hydrolysis rate to glycodeoxycholic acid (GDCA) by 91.62%. Genomic sequencing and bioinformatics analysis indicated that gene bsh1 was associated with BSH activity of Lp. plantarum Lp20 and gene deletion of bsh1 confirmed the role of Bsh1 in GDCA hydrolysis. To investigate if the Bsh1 from Lp. plantarum Lp20 could alleviate obesity, the wild type and bsh1 deletion mutant strains were administered daily for 8 weeks to diet-induced obese mice, respectively. Compared with mutant strain, the wild type strain Lp20 significantly reduced body weight gain, inguinal white adipose tissue and mesenteric fat mass in obese mice. In addition, Lp20 also reduced serum total cholesterol levels and LDL-C by 20.8% and 33.3%, respectively. Furthermore, the recovered liver steatosis was only observed in Lp. plantarum Lp20 treated mice. Taken together, the bile salt hydrolase Bsh1 from Lp. plantarum Lp20 was a key functional factor on ameliorating HFD-induced obesity by reducing cholesterol levels and suppressing adipogenesis in mice.

Despite extensive research, the links between the accumulation of glycosaminoglycans (GAGs) and the clinical features seen in patients suffering from various forms of Mucopolysaccharidoses (MPSs) have yet to be further elucidated. This is particularly true for the neuropathology of these disorders, even though the neurological symptoms are currently incurable, even in the cases where a dis-ease-specific therapeutic approach does exist. One of the best ways to get insights on the molecular mechanisms driving that pathogenesis is the analysis of patient-derived cells. Yet, not every pa-tient-derived cell holds potential to recapitulate relevant disease features. For the neurodegenerative forms of these diseases in particular, it is challenging to grow neuronal cultures that accurately represent them because of the obvious inability to access live neurons. This scenario changed sig-nificantly since Yamanaka et al. published their protocol for induction of pluripotent stem cells (SC) from adult human fibroblasts. From then on, a series of differentiation protocols to generate neurons from induced pluripotent stem cells (iPSC) was developed and extensively used for disease mod-eling. Currently, human iPSC and iPSC-derived cell models have been generated for several MPS and numerous lessons were learnt from their analysis. Here we review most of those studies, not only listing the currently available MPS iPSC lines and their derived models, but also summarizing how they were generated and the major information different groups have gathered from their analysis. Finally, and taking into account that iPSC generation is a laborious/expensive protocol that holds significant limitations, we also comment on a tempting alternative to establish MPS pa-tient-derived neuronal cells in a much more expedite way by taking advantage of the existence of a population of multipotent SC in human dental pulp, to establish mixed neuronal and glial cultures.

This study investigates the possibility of using machine learning models created in DeepLabCut and Create ML to automate aspects of behavioral coding and aid in behavioral analysis. Two models with different capabilities and complexities were constructed and compared to a manually observed control period. The accuracy of the models was assessed before being applied to 7 nights of footage of the nocturnal behavior of two African elephants (Loxodonta africana). The resulting data was used to draw conclusions regarding behavioral differences between the two elephants and between individually observed nights, thus proving that such models can aid researchers in be-havioral analysis. The models were capable of tracking simple behaviors with high accuracy, but had certain limitations regarding detection of complex behaviors, such as the stereotyped behavior sway, and displayed confusion when deciding between visually similar behaviors. Further expansion of such models may be desired to create a more capable aid with the possibility of automating behavioral coding.

This study evaluates audiogenic epilepsy in Krushinsky-Molodkina rats using a wireless EEG system to overcome the limitations of traditional methods that restrict animal movement. Nine male KM rats, prone to audiogenic seizures, were implanted with electrodes in areas critical for seizure activity (inferior colliculus, ventrolateral periaqueductal gray, dorsal area of the secondary auditory cortex, and motor cortex). This setup allowed for the observation of seizures without movement restriction. Results showed that targeted neural intervention via electrode implantation reduced the intensity of convulsive seizures in half of the subjects, suggesting a potential therapeutic approach. The severity of seizures was influenced by the pre-phonostimulation EEG background activity in specific brain regions, identifying them as key in the genesis and generalization of seizures. Observations of dual generalized seizure waves and induced hyperkinesis challenge conventional epilepsy models and suggest new directions for research and therapy development.

Human Activity Recognition (HAR) technology enables continuous behavior monitoring, particularly valuable in healthcare. This study investigates the viability of using an ear-worn motion sensor for classifying daily activities, including lying, sitting/standing, walking, ascending stairs, descending stairs, and running. Fifty healthy participants (between 20 and 47 years old) engaged in these activities while under monitoring. Various machine learning algorithms, ranging from interpretable shallow models to state-of-the-art deep learning approaches designed for HAR, were employed for classification. Results demonstrate the ear sensor's efficacy, with deep learning models achieving 98% accuracy rate of classification. The obtained classification models are agnostic regarding which ear the sensor is worn and robust against moderate variations in sensor orientation (e.g., due to differences in auricle anatomy), meaning no initial calibration of the sensor orientation is required. The study underscores the ear's efficacy as a suitable site for monitoring human daily activity and suggests its potential for combining HAR with in-ear vital signs monitoring. This approach offers a practical method for comprehensive health monitoring by integrating sensors in a single anatomical location. This integration facilitates individualized health assessments, with potential applications in tele-monitoring, personalized health insights, and optimizing athletic training regimes.

Cardiac arrest may cause significant hypoxic-ischemic injury leading to coma, seizures, myoclonic jerks, or status epilepticus. Mortality is high but accurate prognostication is challenging. A multimodal approach is employed, in which electroencephalograph (EEG) forms a key part with several recognised patterns of prognostic significance. In this retrospective study, clinical and qualitative features of the EEG of patients admitted to the Intensive Care Unit (ICU) at Kingston General Hospital following cardiac arrest from 2017-2020 were reviewed. The study included 81 adult patients (>18 years). Outcome was assessed using the Cerebral Performance Category as 1-2 (favourable) or 3-5 (unfavourable). EEG patterns were divided into groups within the highly malignant, malignant, and benign patterns described in the literature. There were a wide range of causes and 22% had a favourable outcome. Highly malignant, malignant, and benign patterns were associated with survival in 0%, 78% and 100% respectively and favourable outcomes in 0%, 44% and 100%. All patients with seizures died and 94% with myoclonus had unfavourable outcomes. In contrast, EEG reactivity and improvement on follow-up EEG was associated with a favourable outcome. In conclusion, highly malignant EEG, seizures and myoclonus were associated with unfavourable outcome, while patient with malignant EEG had better outcome.

The split of the brain into two hemispheres is pivotal to human existence, enabling incompatible versions of the world, with quite different priorities and values, to exist concomitantly. Neuroimaging techniques are usually the adopted methods to assess hemispherical bias. However, can differences in thinking orientation, behavioural style, and personality emerging from laterality be observed without the use of neuroimaging techniques? This paper investigates whether a personality test based on the Five-factor model (FFM) is also able to identify hemispherical bias. It does so by testing five hypotheses on personality differences related to handedness. The aim is to contribute to the instantiation of the FFM in neuroscience by testing its validity against the neuroscientific literature on brain laterality. The findings pointed to no statistically significant differences due to handedness in three out of five personality traits (namely, Neuroticism, Conscientiousness and Extraversion). As to the other two traits – Openness and Agreeableness – the hypotheses were only partially confirmed by the data, as the relevant difference found was not between left-handed and right-handed groups, but between ambidextrous and the others.

Studying the multi-function bacterial implications on the natural phytochemicals could be among the best solutions for producing clean-label functional juices. This study aimed to develop a high-quality mulberry juice with enhanced antioxidant capacity through fermentation. The juice was fermented using mono- and co-cultures of Lactobacillus casei (LC), L. plantarum (LP), L. paracasei (LPC), L. acidophilus (LA), and L. helveticus (LH) at different time intervals (24, 48, 72, and 96 h). The total phenolic content (TPC), total flavonoid content (TFC), flavonols, anthocyanins, and proan-thocyanidins were determined, along with the antioxidant activity assays and FTIR analysis. The results revealed significant changes in molecular interactions and functional group presence post-fermentation, indicating microbial incorporation's effect on the juice's functional profile. These changes were attributed to the formation of new compounds during fermentation, such as organic acids, alcohols, glycerol, and phenols, as evidenced by the FTIR spectra. Besides, LC-LA and LC-LPC co-culture treatments yield the most substantial stability in TPC, TFC, and TF after 48 h compared to 24 h and 72 h. After 48 h, the co-cultures of LPC-LH (1265.5 GAE/L) and LPC-LA (1145 GAE/L) were increased the TPC after 48 h than the single cultures. Conclusively, LC-LPC and LP-LPC co-culture fermentation was recommended as a cost-effective method to enhance the an-tioxidant potential and the overall phytochemical capacity of mulberry products. The findings of this study provide valuable insights into the potential of fermented mulberry juice as a functional food with improved health benefits.

Energy generation now heavily relies on the field of photocatalysis. Many conventional research topics have been superseded by the conversion of solar energy into chemical or thermal energy for a variety of energy-related applications. The urgent necessity of moving away from non-renewable energy sources is a result of the problem of global warming. In an effort to create the best photocatalysts for effective solar conversion, scientists are investigating a variety of material systems and material combinations. By examining the influence of morphology changes on the photoelectrochemical activity of zinc oxide nanostructures, here electrodeposition was used to create the nanostructures. By using the proper capping agents, it is possible to control the growth rates of different ZnO facets and get well-defined nanostructures and orientation. In order to generate distinct ZnO morphologies, we report here the electrodeposition of ZnO nanostructured thin films in the presence of different capping agents. A zinc nitrate (Zn (NO₃)₂) bath was used to electrodeposit ZnO nanostructures on indium tin oxide glass (ITO) substrate at 70 °C with an applied potential of -1.0 V. Capping agents such as ethylenediamine (EDA) or ammonium fluoride (NH₄F) were added to this zinc nitrate bath. The photoelectrochemical capabilities of the morphology-controlled zinc oxide nanostructures were extensively evaluated and characterised. Thus various ZnO morphologies had an impact on the PEC properties.

There are various modeling techniques adopted for predicting the labor productivity that incorporate the influence of various factors, but neural networks are found to have strong pattern recognition and higher accuracy to get reliable estimates. To develop a construction labor productivity (CLP) model for concreting activities, data were collected through a questionnaire. The most critical influencing parameters were ranked according to their relative importance index (RII). Then the strength of the relationship between CLP and influencing parameters was analyzed using correlation coefficient results generated in Python program. Finally, the CLP model which represents the output of the crew within a certain factor was successfully developed using artificial neural networks (ANNs). Five objectives and six subjective critical influencing parameters were selected using RII. Crew experience, age of workers, and placement technique are the top three influencing parameters that have a strong relation with CLP with correlation coefficient values of 0.5681, 0.5349, and 0.5227 respectively. The developed model within these influencing parameters has a higher capability to predict the output of labor with a 92% coefficient of determination (R2) and a mean squared error of 0.316%. Therefore, the application of such a model for the accurate estimation of labor productivity is recommended.

Neurological disorders have been reported in a large number of coronavirus disease 2019 (COVID-19) patients, suggesting that this disease may have long-term adverse neurological consequences. COVID-19 occurs from the infection by a positive-sense single-stranded RNA virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The membrane fusion protein of SARS-CoV-2, the spike protein, binds to its human host receptor, angiotensin-converting enzyme 2 (ACE2), to initiate membrane fusion between the virus and host cell. The spike protein of SARS-CoV-2 contains the furin protease recognition site and its cleavage enhances the infectivity of this virus. The binding of SARS-CoV-2 to the ACE2 receptor has been shown to downregulate ACE2, thereby increasing the levels of pathogenic angiotensin II (Ang II). The furin protease cleaves between the S1 subunit of the spike protein with the binding domain toward ACE2 and the S2 subunit with the transmembrane domain that anchors to the viral membrane, and this activity releases the S1 subunit into the blood circulation. The released S1 subunit of the spike protein also binds to and downregulates ACE2, in turn, increasing the level of Ang II. Considering that a viral particle contains many spike protein molecules, furin-dependent cleavage would release many free S1 protein molecules each of which can downregulate ACE2, while the infection with a viral particle only affects one ACE2 molecule. Therefore, the furin-dependent release of S1 protein would dramatically amplify the ability to downregulate ACE2 and produce Ang II. We hypothesize that this amplification mechanism that the virus possesses, but not the infection per se, is the major driving force behind COVID-19 associated neurological disorders.

Many anti-tumor effects of group-specific component-derived macrophage-activating factors (GcMAFs) have been reported; however, the specific mechanisms remain unclear. Controlling tumor-associated macrophages (TAMs) in the tumor microenvironment is essential for cancer treatment. This study assessed the role of GcMAF in macrophage activation, elucidated the mechanisms by which it exerts its anti-tumor effects, and determined its effects on TAMs in the tumor microenvironment. GcMAF-stimulated RAW264.7 macrophages and EMT6 breast tumor cells were co-cultured in a 0.4-µm pore cell culture insert, and gene and protein expression and cell viability were evaluated. DNA microarray analysis of GcMAF-stimulated RAW264.7 cells was conducted. The induction of M2 RAW264.7 cells by interleukin (IL)-4 and IL-13 was analyzed. GcMAF stimulation increased the tumor necrosis factor-α and inducible nitric oxide synthase mRNA and protein levels in RAW264.7 cells but decreased the viability of co-cultured EMT6 cells. These results were confirmed in the M2 RAW264M2.7 cells, suggesting that GcMAF exerts anti-tumor effects by inducing the differentiation of macrophages into the M1 type and reprogramming M2 macrophages to the M1 type. The anti-tumor activity of GcMAF via M2-to-M1 macrophage reprogramming could aid in developing novel cancer immunotherapies.

Tinnitus is a common phantom auditory percept, believed to be related to plastic changes in the brain due to hearing loss. However, tinnitus can also occur in absence of any clinical hearing loss. Then, since there is no hearing loss, the mechanisms that drive plastic changes remain largely enigmatic. Previous studies showed subtle differences in sound-evoked brain activity associated with tinnitus in subjects with tinnitus and otherwise, normal hearing, but the results are not consistent across studies. Here, we aim to investigate those differences using monaural rather than binaural stimuli. Sound-evoked responses were measured using functional magnetic resonance imaging (MRI) in participants with and without tinnitus. All participants had clinically normal audiograms. The stimuli were pure tones with frequencies between 353 and 8000 Hz, presented monaurally. A Principal Component Analysis (PCA) of the response in the auditory cortex revealed no difference in tonotopic organization, which confirmed earlier studies. A GLM analysis showed hyperactivity in the lateral areas of the bilateral auditory cortex. Consistent with the tonotopic map, this hyperactivity mainly occurred in response to low stimulus frequencies. This may be related to hyperacusis, which was associated with tinnitus found in the parahippocampus. This may reflect an interference between tinnitus and spatial orientation.

(1) Background: Alzheimer’s Disease (AD) accounts for 70% of dementia cases and with no effective pharmacological treatments, new rehabilitation methods are needed. Motor activities and transcranial direct current stimulation (tDCS) have shown promise in stabilizing and enhancing cognitive functions. Objective: We want to investigate the effects of combined motor or cognitive activity with tDCS on cognitive functions in AD patients. (2) Methods: Patients with mild or moderate AD were randomized into four groups: motor activity or cognitive activity associated with anodic or sham tDCS (MotA, MotS, CogA, CogS). They received two weeks of treatment (45 minutes, 5 days/week), with the first 15 minutes using 2mA tDCS on the dorsolateral prefrontal cortex. Cognitive assessments were conducted pre-treatment (T0), post-treatment (T1), and one week after (T2). (3) Results: Twenty patients were included. Mann-Whitney test showed significant improvements in anodic groups (MotA+CogA) in the global cognitive status (p=.042), in selective attention (p=.012), and sustained attention (p=.012) at T1, but not at T2. In addition, MotA improved in the Picture Recognition Test (p=.027) and in sustained attention (p=.047) at T2. (4) Conclusion: Combined motor or cognitive activity with anodic tDCS could slow cognitive decline in AD patients, with notable improvements in global cognitive state and attention at T1.

Ophelia syndrome is characterized by the coincidence of severe neuropsychiatric symptoms, classical Hodgkin lymphoma, and the presence of antibodies to the metabotropic glutamate 5 receptor (mGluR5). Little is known about the pathogenetic link between these symptoms and the role that anti-mGluR5-antibodies play. We investigated lymphoma tissue from patients with Ophelia syndrome and with isolated classical Hodgkin lymphoma by quantitative immunocytochemistry for mGluR5-expression. Further, we studied the L-1236, L-428, L-540, SUP-HD1, KM-H2, and HDLM-2 classical Hodgkin lymphoma cell lines by FACS and Western blot for mGluR5-expression, and by transcriptome analysis. mGluR5 surface expression differed significantly in terms of receptor density, distribution pattern, and percentage of positive cells. Highest expression levels were found in the L-1236 line. RNA-sequencing revealed more than 800 genes that were higher expressed in the L-1236 line in comparison to the other classical Hodgkin lymphoma cell lines. High mGluR5-expression was associated with upregulation of PI3K/AKT and MAPK pathways and of downstream targets (e.g. EGR1) known to be involved in classical Hodgkin lymphoma progression. Finally, mGluR5 expression was increased in the classical Hodgkin lymphoma-tissue of our Ophelia syndrome patient in contrast to five classical Hodgkin lymphoma-patients without autoimmune encephalitis. Given the association of encephalitis and classical Hodgkin lymphoma in Ophelia syndrome, it is possible that mGluR5-expression on classical Hodgkin lymphoma cells not only drives tumor progression but also triggers anti-mGluR5 encephalitis even before classical Hodgkin lymphoma becomes manifest.

Introduction: Although aging is a natural phenomenon, in recent years it has accelerated. One key factor implicated in the aging process is oxidative stress. Oxidative stress play also role in frailty (frail) and metabolic syndrome (MetS). Methods: 66 elderly persons (65 years old and older) with no acute or severe chronic disorders were assessed: waist circumference (WC), arterial blood pressure, glycemia, glycated hemoglobin (HbA1c), plasma lipids and activity of erythrocyte superoxide dismutase (SOD-1). Patients were classified as NonMetS-Nonfrail (n=19), NonMetS-frail (n=20), MetS-Nonfrail (n=17), and MetS-frail (n=10). Results: There were no significant differences in superoxide dismutase activity among investigated elderly groups. However, the data suggests that MetS individuals, both frail and nonfrail, have higher risk factors for cardiovascular disease compared to NonMetS individuals. The correlations analyses of SOD-1 and other metabolic indices suggest that SOD-1 levels may be influenced by age, total cholesterol, HDL cholesterol, and fasting glucose levels in certain groups of seniors. Conclusions: Aging is associated with decreased antioxidant enzyme SOD-1 activity with glucose alteration in frailty syndrome as well as with lipids disturbances in metabolic syndrome.

Background: The study demonstrates the sustainable synthesis of translucent zinc oxide (ZnO) nanowires using Moringa seed extract, highlighting eco-friendly and sustainable approaches. Methods: Characterization techniques such as X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), energy dispersive spectroscopy (EDS), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) confirmed the formation of ZnO nanostructures with diverse morphologies, including nanowires and spherical clusters. Results: The synthesized ZnO nanowires exhibited remarkable photocatalytic activity, achieving over 89% degradation efficiency of methylene blue (MB) under UV light within 80 minutes, demonstrating their potential for wastewater treatment applications. Conclusions: The research findings support Sustainable Development Goals (SDGs) related to clean water, climate action, and life below water and on land, highlighting the role of eco-friendly nanostructures in environmental remediation. The dual advantage of Moringa seed extract, providing both a sustainable synthesis route and health benefits due to its rich content of vitamins and phytochemicals, underscores the potential of integrating natural resources in nanotechnology for environmental and health applications.

An eight-sided prism sample, obtained from a hot-rolled AZ31 magnesium alloy sheet, was compressed at room temperature along the transverse direction to investigate the influence of local strain on twinning behavior using electron backscatter diffraction (EBSD) measurements. The octagonal surface of the sample was divided into distinct regions based on hardness distribution and metallographic observations. The EBSD maps of different areas show significant variations, suggesting that these areas experienced different local strain conditions. The EBSD measurements provided detailed data from three distinct regions, with the strain state known in two regions and uncertain in the third. The combined analysis of the Schmid factor (SF) and the strain compatibility factor (m') was employed to study twin variant selection. The comparison of twinning behavior in different regions showed that the strain compatibility factor offered a more comprehensive explanation for the observed twinning pattern in the region with local shear strain.

Magnaporthe oryzae is a filamentous heterothallic ascomycete fungus globally distributed in rice-growing regions and serves as the causative agent of rice blast disease. Populations shaped by environmental factors and human intervention play important roles in the formation of genetic structure. In this study, population structures and spatiotemporal dynamics were investigated based on the large-scale whole genomic sequences of rice-infecting M. oryzae around the world. By analyzing the genetic structures, we identified divergent clades that crossed geographic boundaries. While we observed associations between the isolates and their geographic origins, we also found that there were frequent migration events occurring worldwide. The populations in Asia demonstrated the highest genetic diversity due to the continent’s history of rice domestication, followed by separate gene flows to Africa, North America, South America and Europe. Within Asia, China was the migration origin, facilitating gene flows to Japan and South Korea. Additionally, our analysis of the evolutionary history of global M. oryzae populations provided insights into the population expansion that has taken place in recent decades. Overall, our findings indicate that human-mediated gene flows played a pivotal role in shaping the genetic structure of M. oryzae.

A four-step synthesis of bifunctional, noncovalent organocatalysts based on the chiral (1R,2R)-cyclohexane-1,2-diamine scaffold containing a 1,2-benzenediamine H-bond donor was developed. Nucleophilic aromatic substitution of the 2-fluoronitrobenzene derivative with the commercial (1R,2R)-cyclohexane-1,2-diamine was followed by selective alkylation of the primary amino group, reduction of the aromatic nitro group and final derivatization of the primary aromatic amino group, i.e. acylation, sulfonation, reductive alkylation and arylation, leading to the four subtypes of organocatalysts. All new compounds were fully characterized. The prepared organocatalysts (32 examples) were tested in the Michael addition of acetylacetone to trans-β-nitrostyrene, yielding the addition product with incomplete conversions (up to 93%) and enantioselectivities of up to 41% ee.

To mitigate pyrethroid resistance in mosquito vectors of emerging and re-emerging human pathogens, there is an urgent need to discover insecticides with novel modes of action. Natural alternatives, such as extracts derived from plants, may serve as substitutes for traditional synthetic insecticides if they prove to be sustainable, cost-effective, and safe for non-target organisms. Hemp (Cannabis sativa) is a sustainable plant known to produce various secondary metabolites with insecticidal properties, including terpenoids and flavonoids. The goal of this study was to assess the larvicidal activity of hemp leaf extract on 1st instar mosquito larvae from both pyrethroid-susceptible (PS) and pyrethroid-resistant (PR) strains of Aedes aegypti Another goal was to identify which components of the extracts were responsible for any observed larvicidal activity. We found that methanol extract of hemp leaves induced similar concentration-dependent larvicidal activity against PS (LC50: 4.4 ppm) and PR (LC50: 4.3 ppm) strains within 48 hours. Partitioning of the dried leaf extract between methanol and revealed that full larvicidal activity was restricted to the methanol fraction. Analysis of this fraction by gas chromatography-mass spectrometry and nuclear magnetic resonance showed it to be dominated by cannabidiol (CBD). Larvicidal assays using authentic CBD confirmed this compound was primarily responsible for the toxicity of hemp leaf extract against both strains. We conclude that hemp leaf extracts and CBD have the potential to serve as viable sources for the development of novel mosquito larvicides.

Mild traumatic brain injury (mTBI) or concussion accounts for the bulk of all head injuries and represents a major health concern. Although an mTBI event may not manifest in neurobehavioral impairment, repeated injuries, known as repeated mTBI (rmTBI), can result in a cumulative effect that may progress to long-term cognitive and functional deficits. To date, there is no FDA-approved drug for TBI in general and rmTBI in particular. In previous studies, we have demonstrated the neuroprotective role of mitoquinone (MitoQ), a mitochondrial antioxidant, in an open head injury model and a model of repeated mild TBI (rmTBI) at a chronic time point (30 days). In this work, we set out to assess the neuroprotective potential of MitoQ at acute (3 days) and subacute time points (7 days) post-injury in a controlled cortical impact model of rmTBI. C57BL/6 male mice were injected intraperitoneally with MitoQ (5 mg/kg) one hour after the first mTBI, and three days after the first injury in both the 3-day and 7-day MitoQ + rmTBI subgroups, with an additional injection four days after the second injection in the 7-day group. Cognitive function was evaluated using the Morris water maze (MWM) while gross and fine motor functions were evaluated by the pole climbing, grip strength, and ladder rung tests. Dihydroethidium (DHE) staining was performed to evaluate oxidative stress while qRT-PCR was used to measure the gene expression of different antioxidant enzymes. Also, immunofluorescence staining was performed on brain tissue to assess the degree of microgliosis and astrocytosis. Our results showed that MitoQ conferred significant protection on days 3 and 7 post-injury against fine motor function impairment induced by rmTBI. Moreover, MitoQ enhanced cognitive function and reduced astrogliosis, microgliosis, and levels of oxidative stress on day 7 post-injury. However, antioxidant gene expression generally remained unaffected. In light of our results, MitoQ administration may be considered a preventive approach that helps to alleviate the neurological manifestations associated with rmTBI early before symptoms progress to long-term deficits.