Staphylococcus aureus is a Gram-positive bacterium causing a range of mild to life-threatening infections including bone infections such as osteomyelitis. S. aureus is able to invade and persist within non-professional phagocytic cells such as osteoblasts. In the present study four different S. aureus strains, 2SA-ST239-III, 5SA-ST5-II, 10SA-ST228-I, and 14SA-ST22-IVh were tested for their ability to modulate cell viability in MG-63 osteoblast-like cells following a successful invasion and persistence. Methicillin-sensitive S. aureus (MSSA) ATCC-12598-ST30 was used as control. Despite the demonstrated similar abilities of internalization and persistence of ATCC-12598-ST30, 2SA-ST239-III, and 14SA-ST22-IVh strains in MG-63 osteoblast-like cells under our experimental conditions, we demonstrated that the decrease in cell viability was due to the different behavior of the considered strains, with the number of intracellular bacteria playing a limited role. We focused our attention on different cellular biochemical functions related to inflammation, cell metabolism, and oxidative stress during osteoblast infections. We were able to show that: 1) ATCC-12598-ST30 and 2SA-ST239-III were the only two clones able to persist and maintain their number into the cellular hostile environment during the entire period of infection; 2) 2SA-ST239-III was the only clone able to significantly increase the gene expression (3 and 24 h) and protein secretion (24 h) of both interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in MG-63 osteoblast-like cells; 3) the same clone determined a significant up-regulation of transforming growth factor-β1 (TGF-β1) and the metabolic marker glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNAs at 24 h post infection; 3) neither the MSSA nor the four MRSA strains induced oxidative stress phenomena in MG-63 cells, although a very different expression pattern towards nuclear factor E2-related factor 2 (Nrf2) and its downstream gene heme oxygenase 1 (HO-1) activation was observed among the different clones. Our results can open a new way of considering therapies, going in the direction of an individualized therapeutic strategy that should take into account the difference existing between MSSA and MRSA as well as the distinctive features of the different clones. Not only, therefore, a different antibiotic approach but also a starting point for considering different host factors, i.e. the modulation of specific cytokines such as IL-6, TNF-α, and TGF-β1.

The gastrointestinal (GI) tract is innervated by the enteric nervous system (ENS), an extensive neuronal network that traverses along its walls. Due to local reflex circuits, the ENS is capable of functioning with and without input from the central nervous system. The functions of the ENS range from the propulsion of food to nutrient handling, blood flow regulation and immunological defense. Records of it first being studied emerged in the early 19th century when the submucosal and myenteric plexuses were discovered. This was followed by extensive research and further delineation of its development, anatomy, and function during the next two centuries. The morbidity and mortality associated with the underdevelopment, infection or inflammation of the ENS highlights its importance and the need for us to completely understand its normal function. This review will provide a general overview of the ENS to date and connect specific GI disorders such as short bowel syndrome with neuronal pathophysiology. Exciting opportunities in which the ENS could be used as a therapeutic target for common GI diseases will also be highlighted, as the further unlocking of such mechanisms could open the door to more therapy-related advances, and ultimately change our approach to GI disorders.

The asymptotic dynamics of the classes of rational difference equations (RDEs) of third order defined over the positive real-line as $$\displaystyle{x_{n+1}=\frac{x_{n}}{ax_n+bx_{n-1}+cx_{n-2}}}, \displaystyle{x_{n+1}=\frac{x_{n-1}}{ax_n+bx_{n-1}+cx_{n-2}}}, \displaystyle{x_{n+1}=\frac{x_{n-2}}{ax_n+bx_{n-1}+cx_{n-2}}}$$ and $$\displaystyle{x_{n+1}=\frac{ax_n+bx_{n-1}+cx_{n-2}}{x_{n}}}, \displaystyle{x_{n+1}=\frac{ax_n+bx_{n-1}+cx_{n-2}}{x_{n-1}}}, \displaystyle{x_{n+1}=\frac{ax_n+bx_{n-1}+cx_{n-2}}{x_{n-2}}}$$ is investigated computationally with theoretical discussions and examples. It is noted that all the parameters $a, b, c$ and the initial values $x_{-2}, x_{-1}$ and $x_0$ are all positive real numbers such that the denominator is always positive. Several periodic solutions with high periods of the RDEs as well as their inter-intra dynamical behaviours are studied.

Cellular substructure has been widely observed in the sample fabricated by laser powder bed fusion, while its growth direction and the crystallographic orientation have seldom been studied. This research tries to build a general model to construct the substructure from its two-dimensional morphology. All the three Bunge Euler angles to specify a unique growth direction are determined, and the crystallographic orientation corresponding to the growth direction is also obtained. Based on the crystallographic orientation, the substructure in the single track of austenitic stainless steel 316L is distinguished between the cell-like dendrite and the cell. It is found that, with the increase of scanning velocity, the substructure transits from cell-like dendrite to cell. When the power is 200 W, the critical growth rate of the transition in the single track can be around 0.31 ms^-1.

Background: Virtual Reality (VR) is an emerging tool in the management of anxiety, one of the most disturbing symptoms of Alcohol Use Disorder (AUD), which often leads to relapse. Still, patients with Alcohol Use Disorder frequently have a history of Acute Symptomatic Seizures, and they are subsequently excluded from studies using VR because of the hypothesized fear of inducing photosensitive seizures. The first part of this narrative review explores the pathophysiological mechanisms of seizures associated with AUD, specifically acute symptomatic seizures. In contrast, the second part explores virtual reality’s safe use in seizure-prone individuals, highlighting that the current state-of-the-art is based on a biased per-ception and old epidemiological data from studies conducted on photosensitive seizures in the late 90s. VR exposure has yet to be reported as triggering seizures within known pharmacovigilance databases. Significance: The implications weigh heavily on VR research currently associated with this significant adverse event. Further studies are necessary to address the risk of seizures triggered by VR in patients predisposed to developing seizures, like alcohol use disorder patients with a history of acute symptomatic seizures. Such research is essential to ensure that the potential benefits of Virtual Reality as a tool for managing anxiety in individuals with alcohol use disorder and acute symptomatic seizures are not unduly restricted. Furthermore, AUD can also serve as an intervention model feasible to de-bias attitudes toward the current lack of evidence base concerning the significant adverse events of VR-induced seizures, therefore facilitating the clinical implementation of this unharnessed digital treatment interface.

Breast cancer (BC) is the most common invasive neoplasm and affects many women of working age. The return to work (RTW) of female survivors (BCSs) is associated with a better quality of life and longer survival. A tailored intervention to promote RTW was launched in 2022. A year later, the women were contacted to find out if RTW had occurred regularly and what their health conditions were compared to baseline. BCSs reported excessive fatigue, poor sleep quality, anxiety, depression and reduced work ability; these parameters had not improved significantly compared to baseline. Thematic analysis of the interviews confirmed the presence of personal, company and societal factors that could hinder or favor RTW. The interviews demonstrated that, even in an economically developed country that has provided numerous benefits for BCSs, protection is not always effective. Personalized intervention seems necessary to complete the process of reintegrating BCSs into their future working careers.

Edvard Munch, a founder of Expressionism was pre-occupied with depicting his subjective experience and the most prolific painter of self-portraits since Rembrandt. Based on evidence that faces and self-related images are more salient than other objects it is plausible that self-portraits, in which the subject and object are the same, reflect the artist’s state of mind. Although he suffered from a variety of physical and psychological illness Munch was not diagnosed with any specificity in his lifetime. Posthumous diagnoses include schizophrenia, anxiety, bipolar and other disorders. Recent research has revealed altered visual perception in such patients. The present study empirically analysed three stylistic elements of Munch’s painted self-portraits and portraits: contrast, colour and fractal dimension and his painted productivity, to determine if variations correlate with critical life events and if so whether they indicate states of mind. It found significant increases in contrast and colour brightness and persistent high complexity during critical periods supporting the conclusion that Munch is diagnostically best described as suffering from early onset schizophrenia and comorbid social anxiety disorder.

During the COVID-19 pandemic, the spread of the SARS-CoV-2 virus forced many individuals to confront their mortality and worry about losing loved ones also because social distancing policies often made it impossible to say goodbye. Those not directly experiencing loss were inundated with information about COVID-19-related deaths through various media, leading to vicarious grief. This study aims to explore the long-term effects of direct and vicarious mourning on people's mental health during the COVID-19 pandemic. A sample of 171 adults (65% female) aged 19 to 66 years (mean age = 25.8, SD = 8.57) voluntarily participated in an online survey assessing self-reported psychological measures of complicated grief, anxiety, stress, depression, dispositional neuroticism, and situational anxiety using the Fear of COVID-19 Scale. MANOVA tests revealed that individuals experiencing direct mourning had extremely severe scores for anxiety, stress, and fear of COVID-19, while those without personal losses had moderate scores. Participants reporting high media exposure had higher scores for depression and stress. In line with Terror Management Theory, the study supported that people during the COVID-19 pandemic engaged more in proximal defenses than distal ones, taking health-protective measures, experiencing increased anxiety levels toward SARS-CoV-2 infection, and feeling more distressed. Additionally, vicarious mourning was more strongly associated with depression due to emotional empathy with others. The discussion also addresses the strengths and limitations of the study.

Informal dementia home caregiving is viewed negatively and can result in caregiver depression and anxiety from burnout, potentially compromising caregiving. Solutions are unclear, as caregiving relationships are unique—caregiver creation of a graphic memoir may help to mitigate the negative dementia narrative and reduce experienced burnout. This investigation examines the writing of a graphic memoir by one informal dementia home caregiver, created with the help of a cartoon illustrator and a publisher who edited, printed, and made the graphic memoir available at the psychiatric bookstore considered the largest in North America. Mother of the illustrator and the editor and publisher of this graphic memoir, this author provides the perspective taken in this investigation. The analysis, developed by this author, represents psychoanalytic narrative research, serving as the historical method. Aided by email threads between the publisher/caregiver, publisher/printer, and publisher/bookseller, and a published interview with the dementia caregiver are answers to how writing, illustrating, and publishing the graphic memoir affected the caregiver’s narrative reconstruction and burnout. Providing an example for other informal dementia home caregivers similarly to write and illustrate a publishable graphic memoir for their positive narrative reconstruction and to help decrease their depression and anxiety from burnout is the aim.

Abstract Background Fatigue Syndrome (FS) is described as extreme exhaustion following ordinary activities. Sleep deprivation, the use of antidepressants, autoimmune illnesses, and anemia are also risk factors for FS. Symptoms of FS include headache, dizziness, and dyspnea, among others. Objective: This study focused on assessing the prevalence of fatigue syndrome (FS) and its association with depression and anxiety, among the medical students in Saudi Arabia. Methodology In this cross-sectional investigation conducted in 2023, 740 medical students participated. Data were gathered using an online survey, which encompassed four key sections: Sociodemographic details, the 11-item Chalder Fatigue Questionnaire (CFQ), the 9-item Primary Health Questionnaire (PHQ) assessing depression, and the Generalized Anxiety Disorder 7-item (GAD-7) scale. Analyses were performed by the use of SPSS version 25. Results A total of 740 students were surveyed, 417 (56.4%) satisfied the diagnostic requirements for fatigue syndrome (FS), with most of them being females. Furthermore, 234 (31.2%) and 296 (40.8%) of the participants reported having significant anxiety symptoms and depressive symptoms, respectively. FS was positively correlated with symptoms of anxiety and depression (P

The Sars-Cov-2 pandemic led to several needed containing measures that conditioned the onset of depressive, anxiety and post-traumatic stress symptoms in population. These symptoms, espe-cially if not diagnosed and treated, can also occur in patients undergoing surgery with high im-pact on people’s lives, like hysterectomy. To evaluate the post-surgical distress and anx-ious-depressive symptoms following hysterectomy for benign disease focusing on the impact of COVID-19 pandemic. The prospective observational cohort study included patients undergoing hysterectomy for benign disease. Psychologic evaluation through social-demographic question-naires was obtained before surgery (T1), postoperatively (T2), and 3 months after surgery (T3). The HADS (Hospital Anxiety and Depression Scale) was used to evaluate anxious-depressive symptoms and the PCL-5 (Post-traumatic Stress Disorder Checklist for DSM-5) compared the on-set of post-surgical distress and anxiety and depressive symptoms. The pre-COVID-19 pan-demic period was compared to the post-COVID-19 pandemic phase. Patients treated after COVID-19 pandemic showed higher depressive symptoms rate compared to those treated before (p-value=0.02); conversely, pre-COVID-19 patients were more prone to develop a PTSD (p-value=0.04). A significative association between the occurrence PTSD and anxiety-depressive symptoms registered at T2 a (p-value=0.007) and T3 (p-value

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.

The orexin/hypocretin neuropeptide family has emerged as a focal point of neuroscientific research following the discovery that this family plays a crucial role in a variety of physiological and behavioral processes. These neuropeptides serve as powerful neuromodulators, intricately shaping autonomic, endocrine, and behavioral responses across species. Notably, they serve as master regulators of vigilance and stress responses; however, their role in complex processes such as food intake, metabolism, and thermoregulation warrant further investigation. This narrative review provides a journey through the evolution of our understanding of the orexin system, from its initial discovery to the promising progress made in developing orexin derivatives. It goes beyond conventional boundaries, striving to synthesize the multifaceted activities of orexins. Special emphasis is placed on domains such as stress response, fear, anxiety, and learning, in which the authors contributed to the literature with original publications. This article demonstrates the orchestrating role of the orexins in several intricate and integrative physiological processes. It also overviews the advancement of orexin pharmacology, which has already yielded some promising successes, particularly in the treatment of sleep disorders. This interdisciplinary approach to studying neuropeptides unveils their significance as vital connectors between transient functional changes and lasting structural adaptations. Ultimately, it advances our understanding of the intricate physiological and behavioral contributions of the orexin/hypocretin neuropeptide family.

This study investigated whether reciprocal collaborative pedagogy significantly impacts Indonesian electrical engineering polytechnic students in reducing reading anxiety and improving self-efficacy in ESP reading comprehension skills. Fifty Polytechnic students were equally assigned to two groups. Control groups learned in the traditional reciprocal teaching method individually. Experimental group engaged in reciprocal collaborative pedagogy. Each group received a 6-week reading strategy training. E-learning platforms were used in this study as a complementary tool to distribute ESP reading materials, announcements, and the experiment details being taught. The quantitative and qualitative results demonstrated that the tasks in reciprocal collaborative pedagogy positively affects Indonesian electrical engineering polytechnic students' learning experience and outcomes. This pedagogy promotes a productive learning environment through peer interaction, active engagement, and peer group discussions of the whole learning activities, reducing feelings of anxiety and building confidence in ESP-specialized text.

Pure silver as well as silver compounds have been used as antiseptics for centuries. Nowadays, the most frequently applied form of silver is a nanoparticle form. Several studies demonstrate the ability of silver nanoparticles and silver salts to accumulate in the brain of laboratory ani-mals as well as the ability of silver nanoparticles to influence behavioral and cognitive functions of laboratory mammals. For the first time, the influence of a silver salt, in particular, silver citrate on the change dynamics of behavioral and cognitive functions of laboratory mice at the daily oral exposure during 30, 60, 120 and 180 days is investigated in the present research. We observed the anxiety increase after 30 days of the exposure as well as the ability of mice to adapt to the prolonged oral exposure of silver citrate manifested in the anxiety decrease, increase of locomotor activity and the tendency of long-term contextual memory improvement. Increase of locomotor activity and memory improvement might be associated with the sensitivity increase and regarded as compensatory mechanism to anxiety increase. The observed phenomenon is classified as a hormetic effect. A comparison with the analogous study implemented polyvi-nylpyrrolidone coated silver nanoparticles is carried out. It was concluded that the nanoform is more neurotoxic.

Anxiety disorders are among the most common mental disorders worldwide, and often respond incompletely to existing treatments. Selenium, a micronutrient that is a component of several biologically active selenoproteins, is also involved in several aspects of brain functioning, and may exert antidepressant and anxiolytic effects through multiple pathways. The current paper is a scoping review of translational, observational and interventional evidence on the potential role of selenium and its compounds in the management of anxiety and related disorders. Evidence from animal models suggests that this approach may be promising. Though evidence from observational studies in humans is inconsistent and affected by several confounding factors, the available evidence from randomized controlled trials suggests that selenium supplementation may be beneficial in the management of certain anxiety-related conditions, such as anxiety in medically ill patients, prevention of anxiety following exposure to traumatic stress, and obsessive-compulsive disorder. This paper provides a critical evaluation of the existing evidence base, including unanswered questions that could serve as the focus of further research, and outlines the potential benefits and risks associated with the use of selenium in anxiety disorders.

Functional Connectivity analysis using Electroencephalography signals is common. The EEG signals are converted to networks by transforming the signals into a correlation matrix and analyzing the resulting networks. Here, four learning models, namely, Logistic Regression, Random Forest, Support Vector Machine, and Recurrent Neural Networks, are implemented on the correlation matrix data to classify them either on their psychometric assessment or the effect of therapy; The EEG data is trail-based/event-related. The classifications based on RNN provided higher accuracy( 74-88%) than the other three models( 50-78%). Instead of using individual graph features, a correlation matrix provides an initial test of the data. When compared with the time-resolved correlation matrix, it offered a 4-5% higher accuracy. The time-resolved correlation matrix is better suited for dynamic studies here; it provides lower accuracy when compared to the correlation matrix, a static feature.

The burden of COVID-19 pandemic on health systems and the physical and mental health of healthcare workers (HCWs) has been substantial. This cross-sectional study aims to assess the effects of Covid-19 on the psychological wellbeing of mental health workers who provide care to a vulnerable patient population that have been particularly affected during this crisis. A total of 387 HCWs from across a large urban mental health service completed a self-administered questionnaire consisting of socio-demographic, lifestyle and work-based information and validated psychometric scales. Depression and anxiety were measured using the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder Scale (GAD-7) respectively, sleep problems with the Athens Insomnia Scale (AIS), burnout with the Maslach Burnout Inventory (MBI) and resilience with the Resilience Scale-14 (RS-14). Multivariable logistic regression analysis was performed to determine potential mediating factors. Prevalence of burnout was notable, with 52% recording moderate/severe in Emotional Exhaustion, 19.5% moderate/severe in Depersonalisation and 55.5% low/moderate Personal Accomplishment. Over half of all respondents (52%) experienced sleep problems; the presence of depressive symptoms was a significant predictor of insomnia. An increase in potentially harmful lifestyle changes, such as smoking, alcohol consumption and over-eating was also observed. However, high Resilience was reported by 70% of the sample and the importance of this is highlighted. Female gender was associated with increased levels of depression and emotional exhaustion while those with a history of mental health conditions were most at risk of affective symptoms, insomnia and burnout. Overall, our study revealed considerable levels of psychological distress and maladaptive coping strategies but also resilience and satisfaction with organizational support provided. Findings can inform tailored interventions in order to mitigate vulnerability and prevent long-term psychological sequelae.

Telecommuting is a flexible form of work that has progressively spread over the last 40 years and which has been strongly encouraged by the measures to limit the Covid19 pandemic. There is still limited evi-dence on the effects it has on workers' health. In this survey we invited 905 workers of companies that made a limited use of telework to fill out a questionnaire to evaluate: Intrusive leadership of managers (IL), the request for work outside traditional hours (OFF-TAJD), workaholism (BWAS), effort / reward imbalance (ERI), happiness and common mental issues (CMIs), anxiety and depression, assessed by the Goldberg scale (GADS). The interaction between these variables has been studied by structural equation modeling (SEM). Intrusive leadership and working after hours were significantly associated with occu-pational stress. Workaholism is a relevant moderator of this interaction: intrusive leadership significantly increased the stress of workaholic workers. Intrusive leadership and overtime work were associated with reduced happiness, anxiety and depression. These results indicate the need to guarantee the right to disconnect, to limit the effect of the OFF-TAJD. In addition to this, companies should implement policies to prevent intrusive leadership and workaholism.

In the context of the economic and political uncertainty associated with the 2019-nCoV pandemic, it is necessary to determine the socio-psychological factors involved in the transformation of the behavior of insurance consumers under the influence of a biogenic threat. This study measures financial anxiety and its impact on the insurance behavior of Russian citizens. The correlation, comparative, and regression analyses of the financial anxiety of Russian citizens cover three stages of observation: before the start of the 2019 nCoV pandemic (“FA up to 19 nCoV; N = 766), during the period of quarantine measures announced in Russia in March 2020 (“FA 19-nCoV-1”; N = 856), and after the relaxation of quarantine measures at the end of April 2020 (“FA 19-nCoV-2”; N = 963).Psychological analysis data were obtained from the online survey “Financial anxiety (in the context of insurance)”. The questionnaire is psychometrically reliable and easy to use. It includes five measurement scales: MR1—Physical manifestations of financial incentive anxiety, MR2—With money shortages and financial uncertainty, MR3—The value of insurance coverage, MP4—Financial Confidence, and MR5—Perception of insurance and investment risks. It was found that Russian citizens consider it important to have insurance coverage for a “rainy day”, and they showed confidence in the insurance market during the biogenic crisis. However, unfortunately, during the 19-nCoV-1 and 19-nCoV-2 periods, Russian citizens did not feel financially secure, unlike in the period before 19-nCoV. Women showed high scores for physical manifestations of financial anxiety and low financial confidence in the future, in contrast to men, regardless of the observation period.

In the context of economic and political uncertainty associated with the 2019-nCoV pandemic, it is necessary to determine the socio-psychological factors in the transformation of the behavior of insurance consumers under the influence of the biogenic threat. This study is devoted to measuring financial anxiety and its impact on the insurance behavior of Russian citizens. Correlation, comparative and regression analyzes of financial anxiety of Russian citizens cover three stages of observation: before the start of the 2019 nCoV pandemic (“FA up to 19 nCoV; N = 766), during the period of quarantine measures announced in Russia in March 2020 (“ FA 19- nCoV-1 "; N = 856) and after the relaxation of quarantine measures at the end of April 2020 (" FA 19-nCoV-2 "; N = 963). Psychological analysis data were obtained from the online survey "Financial anxiety (in the context of insurance)". The questionnaire is psychometrically reliable and easy to use, including 5 measurement scales: MR1. Physical manifestations of financial incentive anxiety, MR2. With money shortages and financial uncertainty, MR3. The value of insurance coverage, MP4. Financial Confidence, MR5. Perception of insurance and investment risks. Russian citizens considered it important to have insurance coverage on a “rainy day” and showed confidence in the insurance market during the biogenic crisis. But, unfortunately, Russian citizens during the 19-nCoV-1 and 19-nCoV-2 periods did not feel financially secure in the future, unlike the period before 19-nCoV. ”Women showed high scores for physical manifestations of financial anxiety and low financial confidence in the future, in contrast to men, regardless of the observation period.

Respiratory syncytial virus (RSV) infection is a major cause of severe respiratory disease in infants and young children worldwide. Two vaccines targeting the elderly and pregnant women have been recently approved employing the prefusion form of the RSV-fusion protein (F). However, there are currently no vaccines for infants. Studies have shown a fusion-inactive prefusogenic F form is significantly more immunogenic and produces higher antibody titers to both the prefusion and postfusion structures of the F protein. Here we have developed RSV virus-like particles (RSV-VLPs) consisting of prefusogenic F, RSV glycoprotein and matrix proteins, produced them using the baculovirus expression system, and studied their protective efficacy in Balb/c mice. Morphology and successful assembly of VLPs were confirmed by transmission electron microscopy and western blot. Mice immunized with VLPs developed high levels of serum IgG and neutralizing antibodies as compared with mice immunized with inactivated virus. The VLP vaccine also induced higher levels of IFNγ and IL4, elicited limited proliferation of CD4+ and CD8+ T cells but higher cytotoxic-T-lymphocyte responses. VLP immunization abolished lung pathology in the mice after RSV challenge. Overall, our results indicate that RSV-VLPs consisting of prefusogenic F, glycoprotein and matrix proteins are a potential vaccine candidate against RSV.

The CACCC-box motif emerges as a pivotal cis-regulatory element implicated in diverse developmental processes and diseases, particularly cardiovascular diseases (CVDs). This study centers on the intricate interplay between the CACCC-box and its binding proteins such as: the Krüppel-like family (KLF) of transcription factors as primary effectors in the context of CVDs. Our analysis was through a bioinformatics approach, which reveal significant transcriptional activity among KLF subgroup 2, exhibiting the highest number of interactions focusing on the established roles: pluripotency, cancer, and cardiovascular development and diseases. Our analysis reveals KLF's interactions with GATA4, MEF2C, NKX2.5 and other ~ 90 potential genes that participate in the regulation of the hypertrophic environment (or CVD's Environment). Also, the GO analysis showed genes containing the motif CACCC were enriched for multiple CVD’s, in combination with STRING analysis these results pointed to a link between KLFs and these diseases. The analysis further identifies other potential CACCC-box binding factors, such as SP family members, WT1, VEZF1, and -SALL4, which are implicated in cardiac contraction, remodeling, and inflammation processes.

Chlamydia trachomatis (Ct) infections are the most common sexually-transmitted infection (STI). Despite effective antibiotics for Ct, undetected infections or delayed treatment can lead to infertility, ectopic pregnancies, and chronic pelvic pain. Besides humans, chlamydia poses similar health challenges in animals such as C. suis (Cs) in pigs. Based on the similarities between humans and pigs as well as their chlamydia species, we use pigs as a large biomedical animal model for chlamydia research. In this study, we use the pig model to develop a vaccine candidate against Ct. The vaccine candidate consists of TriAdj-adjuvanted chlamydial protease-like activity factor (CPAF) protein. We tested two weekly administration options – twice intranasal (IN) followed by twice intramuscular (IM), or twice IM followed by twice IN. We assessed the humoral immune response not only in serum by CPAF-specific IgG including antibody avidity determination but also in cervical and rectal swabs by CPAF-specific IgG and IgA ELISAs. The systemic T-cell response was analyzed upon in vitro CPAF-restimulation via IFN-γ and IL-17 ELISpots as well as intracellular cytokine staining flow cytometry. Our data demonstrate that while the IN/IM vaccination mainly led to non-significant systemic immune responses, the vaccine candidate is highly immunogenic if administered IM/IN. This vaccination strategy induced high serum anti-CPAF IgG levels with strong avidity as well as high IgA and IgG levels in vaginal and rectal swabs and in uterine horn flushes. In addition, this vaccination strategy prompted a pronounced cellular immune response: Besides inducing IL-17 production, the vaccine candidate induced a strong IFN-γ response by CD4 T cells. In the IM/IN vaccinated pigs, these cells also significantly downregulated their CCR7 expression – a sign for differentiation into peripheral tissue homing effector/ memory cells. Conclusively, this study demonstrates strong immunogenicity of the IM/IN administered TriAdj-adjuvanted Ct CPAF vaccine candidate. Future studies will test vaccine efficacy of this promising Ct vaccine candidate. In addition, this project demonstrates suitability of the Cs pre-exposed outbred pig model for Ct vaccine development. Thereby, we aim to open the bottleneck of large animal models to facilitate the progression of Ct vaccine candidates into clinical trials.

Recent studies have elucidated the diversity of genes encoding venom in sea anemones. However, most of those genes are yet to be explored in an evolutionary context. Insulin is a common peptide across metazoans and has been coopted into a predatory venom in many venomous lineages. In this study, we focus on the diversity of insulin-derived venoms in sea anemones and on elucidating their evolutionary history. We sourced data for 34 species of sea anemones and found sequences belonging to two venom families that have Insulin PFAM annotations (Cono-Insulin, VP302). Our findings show that both families have undergone duplication events. Members of each of the independently evolving clades have consistent predicted protein structures and distinct dN/dS values. Our work also shows that VP302 is part of a multidomain venom contig and has experienced a secondary gain into the venom system of cuticulate sea anemones.

Objective: To analyze the relation between alterations in the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis during the first 6 months of life and weight in children born in the Lower Middle São Francisco region. Methods: This is an analytical cohort, with a quantitative approach and a translational perspective. Thirty children with low and normal birth weight were initially identified in a hospital and reapproached at 3 and 6 months of age. Birth weight and alterations in GH/IGF-1 curves at birth, third month, and sixth month of life. Results: Weight gain during the 6 months of follow-up in newborns with low birth weight was greater compared to newborns with normal birth weight. All children who were born with low birth weight had an altered GH/IGF-1 curve at birth (p = 0.002). Most newborns with low birth weight maintained the alteration in the GH/IGF-1 curve at the third month of life (p = 0.027). Regarding the GH/IGF-1 curve at the sixth month, alteration persisted in greater proportion among children with low birth weight. Conclusion: Alterations in insulin resistance markers, demonstrated by increased GH without a proportional increase in IGF-1, were observed to be significant in children with low birth weight, with greater adiposity in this group, which may increase the risk of metabolic diseases in later life.

Polo-like kinase 1 (PLK1) plays a pivotal role in cell division regulation and emerges as a promising therapeutic target for cancer treatment. Consequently, the development of small-molecule inhibitors targeting PLK1 has become a focal point in contemporary research. The adenosine triphosphate (ATP)-binding site and the polo-box domain in PLK1 present crucial interaction sites for these inhibitors, aiming to disrupt the protein's function. However, designing potent and selective small-molecule inhibitors can be challenging, requiring a deep understanding of protein-ligand interaction mechanisms at these binding sites. In this context, our study leverages the fragment molecular orbital (FMO) method to explore these site-specific interactions in-depth. Through the FMO approach, we used the FMO method to elucidate the molecular mechanisms of small-molecule drug binding to these sites to design PLK1 inhibitors that are both potent and selective. Our investigation further entailed a comparative analysis of various PLK1 inhibitors, each characterized by distinct structural attributes. This comparison enhanced our understanding of the structure-activity relationships of these inhibitors, underscoring the efficacy of the FMO method in identifying critical binding features and predicting binding modes for small-molecule ligands. Furthermore, Our research spotlighted "hot spot" residues instrumental for selective and robust PLK1 binding. Our findings offer profound insights, priming the rational design of innovative potential PLK1 inhibitors with significant implications for developing anticancer therapeutics.

With the increment of the aging population in recent years, neurodegenerative diseases exert a major global disease burden, essentially as a result of the lack of treatments that can stop the disease progression. Alzheimer’s Disease (AD) is an example of a neurodegenerative disease, that affects millions of people globally, with no effective treatment. Natural compounds have emerged as a viable therapy to fill a huge gap in AD management, and in recent years, mostly fuelled by the Covid-19 pandemic, RNA-based therapeutics have become a hot topic in the treatment of several diseases. Treatments of neurodegenerative diseases face significant limitations due to the complex and interconnected pathways that lead to their hallmarks and, also due to the necessity to cross the blood–brain barrier. Nanotechnology has contributed to surpass this bottleneck in the treatment of AD, by promoting safe and enhanced drug delivery to the brain. In particular, exosome-like nanoparticles, a hybrid delivery system combining exosomes and liposomes' advantageous features, are demonstrating great potential in the treatment of central nervous system diseases.

In this work, we present a new way to study the genetic code mathematical and chemical structure, based on the use of mathematical computations involving some few recently designed Fibonacci-like sequences, the “seeds” (“initial conditions”) of which are chosen according to the chemical and physical data of the three amino acids serine, arginine and leucine, playing a prominent role in a recent symmetry classification scheme of the genetic code. It appears that these mathematical sequences, of the same kind as the famous Fibonacci series, apart from their usual recurrence relations, are highly interwinned by many useful linear relationships. Using these sequences and also various sums or linear combinations of them, we derive several physical and chemical quantities of interest, as the number of total coding codons, 61, obeying various degeneracy patterns, the detailed number of hydrogen atoms, the detailed number of atoms (H/CNOS) and the integer molecular mass (or nucleon number), in the side chains of the 61 “amino acids”, also in various degeneracy patterns, in agreement with those described in the literature. Also, unexpectedly but interestingly, we find, as a by-product, an accurate description of the very chemical structure of the four ribonucleotides uridine monophosphate (UMP), cytidine monophosphate (CMP), adenosine monophosphate (AMP) and guanosine monophosphate (GMP), the building blocks of RNA whose groupings, in three units, constitutes the triplet codons. In summary, we find a full mathematical and chemical connection with the “ideal sextet’s classification scheme” mentioned above as well as with several others, notably, the Findley-Findley-McGlynn symmetrical classification. We organize the content of the text in such a way that, besides the presentation of several new research results, it has also an educational dimension. The paper could therefore be read and the computations easily worked out, also by non-experts with mathematical background.

The increasing prevalence of depression worldwide requires more effectiveness in therapy approaches and a molecular understanding of antidepressants mode of action. We carried out untargeted metabolomics of the prefrontal cortex of rats exposed to chronic social isolation (CSIS), a rat model of depression, and/or fluoxetine treatment using liquid chromatography-high resolution mass spectrometry. The behavioral phenotype was assessed by the forced swim test. To analyze metabolomics data, univariate and multivariate analysis and biomarker capacity assessment using the classical receiver operating characteristic (ROC) curve were used. Support vector machine-linear kernel (SVM-LK), as a machine-learning algorithm was performed for binary classification. Upregulated myo-inositol following CSIS may represent a potential marker of depressive phenotype. Effective fluoxetine treatment reversed depressive-like behavior and increased sedoheptulose 7-phosphate, hypotaurine, and acetyl-L-carnitine contents, which were identified as potential markers. We identified 4 or 10 marker candidates with ROC curve greater than 0.9 for CSIS or fluoxetine effectiveness designation. SVM-LK has given accuracy of 61.50%, or 93.30%, and 7 or 25 predictive metabolites for CSIS vs. control and fluoxetine-treated CSIS vs. CSIS classification. Overall, metabolic fingerprints combined with ROC curve and SVM-LK may represent a new approach to identifying potential markers or predicting metabolites for group designation or classification.

In general, isolators and dampers used in seismically isolated buildings are designed to be isotropic in any horizontal direction. However, in the case of buildings with plan irregularities, their nonlinear responses depend on the direction of seismic loading. To discuss the influence of the angle of seismic incidence (ASI) on the nonlinear response of irregular building structures, it is important to define the angle of the critical axis of the horizontal ground motion. One possible choice is the “principal axis of ground motion” proposed by Arias (1970). However, because this principal axis is independent of the natural period of a structure, it could be complicated to use for seismically isolated structures with long natural periods. In this study, the influence of the ASI of long-period pulse-like seismic input on an irregular base-isolated building is investigated. First, the angle of the principal axis of ground motion is defined in terms of the cumulative energy input. Then, a nonlinear time-history analysis of a five-story irregular base-isolated building is performed using 10 long-period pulse-like ground motion records considering various ASIs. The results show that, compared with the principal axis of ground motion proposed by Arias, defining the principal axis of ground motion in terms of the cumulative energy input is more suitable for discussions concerning the influence of the ASI on the response of an irregular base-isolated building.

The recent developments in the delivery and design of transcription factors put their therapeutic applications within reach, exemplified by cell replacement, cancer differentiation and T-cell based cancer therapies. The success of such applications depends on the efficacy and precision in the action of transcription factors. The biophysical and genetic characterization of the paradigmatic prokaryotic repressors, LacI and TetR and the designer transcription factors, TALE and CRISPR-Cas9 revealed common rules, which can help the optimization of activators and repressors. Further studies will be required to analyze the linkage between dissociation constants and enzymatic activity, the role of phase separation and squelching in activation and repression, and the long-range interaction of transcription factors with epigenetic regulators in the context of the chromosomes. Understanding these mechanisms will help to tailor systematically optimized designer transcription factors to the needs of specific applications.

In this paper, we study the weak gravitational deflection angle of relativistic massive particles by the Kerr-like black hole in the bumblebee gravity model. In particular, we focus on weak field limits and calculate the deflection angle for a receiver and source at a finite distance from the lens. To this end, we use the Gauss-Bonnet theorem of a two-dimensional surface defined by a generalized Jacobi metric. The spacetime is asymptotically non-flat due to the existence of a bumblebee vector field. Thus the deflection angle is modified and can be divided into three parts: the surface integral of the Gaussian curvature, the path integral of a geodesic curvature of the particle ray and the change in the coordinate angle. In addition, we also obtain the same results by defining the deflection angle. The effects of the Lorentz breaking constant on the gravitational lensing are analyzed. We then consider the finite-distance correction for the deflection angle of massive particles.

Ebola Virus Disease (EVD) is one of the most lethal transmissible infections characterized by a high fatality rate, and caused by members of the Filoviridae family. The recent large outbreak of EVD in West Africa (2013-2016), highlighted the worldwide danger of this disease and its impact on global public health and economy. The development of highly needed anti-Filoviridae antivirals has been so far hampered by the shortage of tools to study their life cycle in vitro, and therefore screen for potential active compounds outside a biosafety level-4 (BSL-4) containment. Importantly, the development of surrogate models to in vitro study of Filoviridae entry in a BSL-2 setting, such as viral pseudotypes and Ebola virus like particles, tremendously boosted both our knowledge on viral life cycle and the identification of promising anti-Filoviridae compounds interfering with viral entry. In this context, the combination of such surrogate systems with large-scale small molecule compounds and haploid genetic screenings, as well as rational drug design and drug repurposing approaches will prove priceless in our quest for the development of a treatment for EVD.

Tissue-like phantoms are widely used as a model for mimicking the optical properties of live tissue. This paper presents the results of a diffusion reflection method as well as fluorescence lifetime imaging microscopy measurements of fluorescein-conjugated gold nanorods in solution as well as inserted in solid tissue-imitating phantoms. A lack of consistency between the fluorescence lifetime results of the solutions and the phantoms raises a question about the ability of tissue-like phantoms to maintain the optical properties of inserted contrast agents.

Trait anxiety, emotion regulation strategies, and metacognitive beliefs influence executive functions (EF) and academic achievement. This study examines their interplay and impact on academic success. In total, 275 adolescents (10-17 years) and parents completed an online questionnaire assessing trait anxiety, emotion regulation strategies, metacognition, parent-reported behaviors related to executive functioning, and overall school average. Preliminary analyses confirmed consistency with existing literature for each variable and their interaction. Furthermore, we conducted a network analysis among the main variables. This analysis supports the need to pay more attention to reflective variables - maladaptive emotion regulation strategies and metacognitive beliefs about worry - when studying trait anxiety. These variables were linked to problematic executive functioning in adolescents. These latter had a negative link to academic achievement. This study offers innovative insights by investigating less-explored relationships in the scientific literature. It reveals high and significant correlations between metacognitive beliefs, maladaptive emotion regulation strategies and trait anxiety (r > .500, p < .001) but also between these variables and both executive functioning and academic achievement. These findings offer new perspectives for research and underscore the importance of holistically examining psychological factors related to academic success.

Cancer patients may experience significant distress. The “Emotion Thermometers” (ETs) are a short visual analogue scale used to screen patients for psychosocial risk. This study aimed to assess emotional distress in a large sample of cancer patients attending psychological services at an NGO, and to explore factors that may contribute to it. The ETs were answered by 899 cancer patients. They were, on average, 59.9 years old, the majority were female, had breast cancer, were under treatment or were disease-free survivors, and reported high levels of emotional distress, above the cut-off (≥5). A Generalized Linear Model was used to measure the association between the level of Distress and 33 items of the problem list. Four items - sadness, depression, sleep and breathing - were found to be significantly related to a higher level of Distress. Additionally, women and those who were in the palliative phase also had significantly higher levels of Distress. Conclusions: The results confirm the need for early emotional screening in cancer patients, as well as the relevance of attending to the characteristics of each patient. Additionally, they highlight the utility of the ETs for the clinical practice, allowing to optimize the referral to specialized psy-chosocial services.

The fear of missing out (FoMO) is characterized in the literature as a fear that others are having rewarding experiences while one is missing out, and a constant need to keep connected with one’s social network. Driven by Social Determination Theory (SDT) FoMO has been linked with Problematic Social Networking Sites use (PSNSU), negative affectivity (NA), self-esteem (SE) and sleep disturbances. The present study reports findings from 512 individuals (79.1% women, mean age 30.5 years, SD= 8.61). Structural equation modelling (SEM) suggests that the duration of SNSs use and the numbers of SNSs platforms actively used partially mediated the relationship between FoMO and PSNSU. In turns, PSNSU partially mediated the relationship between FoMO and NA. Furthermore, the present study has extended the literature by incorporating the Vulnerability Model in the FoMO concept, identifying that SE partially mediated the relationship between FoMO and NA, while NA fully mediated the relationship between FoMO and sleeping disturbances. Accordingly, the present has extended previous research findings in showing exercise as a potential protective factor to prevent against FoMO. Practical and theoretical implications are discussed.

The COVID-19 pandemic has become a public health emergency of international concern, which may affect lifestyle habits and mental health. Based on national health profile assessments, this study investigates perceived changes of lifestyle habits in response to the COVID-19 pandemic and associations between perceived lifestyle changes and mental health in Swedish working adults. Among 5,599 individuals (50% women, 46.3 years), the majority reported no change (sitting 77%, daily physical activity 71%, exercise 69%, diet 87%, alcohol 90%, and smoking 97%) due to the pandemic. Changes were more pronounced during the first wave (April-June) compared to the second (October-December). Women, individuals <60 years, having a university degree, being white-collar workers and having unhealthy lifestyle habits at baseline had higher odds of changing lifestyle habits compared to their counterparts. Negative changes in lifestyle habits as well as more time in mentally passive sitting at home was associated with higher odds of mental ill-health (including health anxiety regarding one’s own and relatives’ health, generalized anxiety and depression symptoms, and concerns regarding employment and economy). The results em-phasize the need to support healthy lifestyle habits to strengthen the resilience in vulnerable groups of individuals to future viral pandemics, and prevent health inequalities in society.

In chronic hepatitis C (CHC) patients, interferon-based treatments showed toxicity, limited efficacy, and psychiatric manifestations. Direct-acting antiviral (DAA) agents appeared safer, though it remains unclear if they may exacerbate or foster mood symptoms in drug-naïve CHC patients. We evaluated 62 CHC patients’ mental status, before and 12 weeks after DAA therapy, by assessment scales and psychometric instruments. We subdivided patients into two groups, CHC patients with (Group A) or without (Group B) a current and/or past psychiatric history. After DAA treatment, Group A patients showed low anxiety and improved depression, no variation in self-report distress, but worse general health perceptions. No significant difference emerged from coping strategies. Depression and anxiety improved in Group B, and no change emerged from total self-reported distress, except for somatization. Moreover, Group B increased problem-focused strategies for suppression of competing activities, and decreased strategies of instrumental social support. Contrarily, Group B reduced significantly emotion-focused strategies, such as acceptance and mental disengagement, and improved vitality, physical and social role functioning. DAA therapy is safe and free of hepatological and psychiatric side effects in CHC patients, regardless of current and/or past psychiatric history. In particular, patients without a psychiatric history also remarkably improved their quality of life.

The workplace is an ideal setting for health promotion. The regular medical examination of workers enables us to screen for numerous diseases, spread good practices and correct lifestyles, and obtain a favourable risk/benefit ratio. The continuous monitoring of the level of workers' wellbeing using a holistic approach that goes beyond the simple prevention of occupational risks enables us to promptly identify problems in work organization and the company climate. Problems of this kind can be adequately managed by using a participatory approach. In this study participatory ergonomics groups were used to improve occupational life in a small company. After intervention we observed a reduction in levels of perceived occupational stress measured with the effort / reward imbalance model, and an improvement in psychological wellbeing assessed by means of the Goldberg anxiety / depression scale. Although the limited size of the sample calls for a cautious evaluation of this study, the GEP© strategy proved to be a useful tool due to its cost-effectiveness.

The conservation of the main protease in viral genomes, combined with the absence of a homologous protease in humans, makes this enzyme family an ideal target for developing broad-spectrum antiviral drugs with minimal host toxicity. GC-376, a peptidomimetic 3CL protease inhibitor, has shown significant efficacy against coronaviruses. Recently, a GC-376-based PROTAC was developed to target and induce the proteosome-mediated degradation of the dimeric SARS-CoV-2 3CLPro protein. Extending this approach, the current study investigates the application of the GC-376 PROTAC to the 3CPro protease of Enteroviruses, specifically characterizing its interaction with CVB3 3CPro through X-ray crystallography, NMR and biophysical techniques. The present structural data show that there are some changes between the binding of CVB3 3CPro and SARS-CoV-2 3CLPro, but the overall similarity is strong. The most notable variation is the orientation of the phenylmethyl ester of GC-376 with the S4 subsite of the proteases. This is linked to the flexibility of the protein structure around the region of the catalytic triad shown by our NMR data. Other structural variations include distinct ligand interactions in subsites S1 and S2, influenced by the presence of Glu71 in CVB3 3CPro. Despite these differences, the GC-376 PROTAC fits well within the binding sites of both proteases, demonstrating its potential as a broad-spectrum antiviral agent.

Improving photobioreactor performance for microalgae cultivation has attracted many researchers over the past years. One of the primary challenges associated with existing photobioreactors is the light penetration. An effective photobioreactor design should maximize light penetration, ensuring uniform illumination throughout the reactor. This study aims to assess the impact of light intensity on microalgal growth from the perspective of energy efficiency and productivity in two photobioreactors. A novel cactus-like and a cylindrical photobioreactor were designed and fabricated using 3D printing technology. These two photobioreactors were used to cultivate two strains of microalgae. The novel photobioreactor achieved a maximum biomass productivity of 0.99 g/L/d and a maximum energy efficiency of 0.3139 g/d/kWh. The cylindrical photobioreactor reached a maximum biomass productivity of 0.74 g/L/d and 0.2199 g/d/kWh of energy efficiency. The increase in biomass productivity can be linked to enhancements in the photobioreactor's surface-to-volume ratio and better light utilization.

In the majority of children with growth hormone (GH) deficiency (GHD), normal GH secretion may occur before the attainment of final height. The aim of the study was to assess the incidence of persistent and transient GHD and the effectiveness of recombined human GH (rhGH) therapy in children with isolated idiopathic GHD, with respect to the moment of therapy withdrawal and according to different diagnostic criteria of GHD. Analysis included 260 patients (173 boys, 87 girls) with isolated idiopathic GHD who completed rhGH therapy and have reassessed GH and IGF-1 secretion. The incidence of transient GHD with respect to different pre- and post-treatment criteria was compared together with assessment of GH therapy effectiveness. Incidence of transient GHD, even with respect to pediatric criteria was very high. Normal GH secretion occurred before the attainment of near-final height. Application of more restricted criteria decreased the number of children diagnosed with GHD but not the incidence of transient GHD among them. Poor response to GH therapy was observed mainly in patients with normal IGF-1 before treatment, suggesting that diagnosis of GHD may be false positive. Further efforts should be made to avoid overdiagnosis GHD and overtreatment of the patients.

Natural killer (NK) cells play a crucial role in innate immunity, particularly in combating infections and tumors. However, in hematological cancers, NK cells often exhibit impaired functions. Therefore, it is very important to activate its endosomal toll-like receptors (TLRs) as a potential strategy to restore its antitumor activity. We stimulate NK cells from the peripheral blood mononuclear cells from children with acute lymphoblastic leukemia and NK cells isolated, the NK cells were stimulated with specific TLR ligands (Poly I:C, Imiquimod, R848, and ODN2006) and evaluated changes in IFN-γ, CD107a, NKG2D, NKp44 expression, Granzyme B secretion, cytokine/chemokine release, and cytotoxic activity. Results revealed that Poly I:C and Imiquimod enhanced activation of both immunoregulatory and cytotoxic NK cells, increasing IFN-γ, CD107a, NKG2D, and NKp44 expression. R848 activated immunoregulatory NK cells, while ODN2006 boosted CD107a, NKp44, NKG2D, and IFN-γ secretion in cytotoxic NK cells. R848 also increased secretion of various cytokines/chemokines. Importantly, R848 and ODN 2006 significantly improved cytotoxicity against leukemic cells. Overall, TLR stimulation enhances NK cell activation, suggesting TLR8 (R848) and TLR9 (ODN 2006) ligands as promising candidates for antitumor immunotherapy.

The pandemic SARS-CoV-2 continues to evolve to give rise to variants of concern that can escape vaccine-induced immunity. As such, more effective vaccines are urgently needed. In this study, we evaluated virus-like particle (VLP) as a vaccine platform for SAS-CoV-2. The spike, envelope, and membrane proteins of the SARS-CoV-2 Wuhan strain were expressed by a single recombinant baculovirus BacMam and assembled into VLPs in cell culture. The morphology and size of the SARS-CoV-2 VLP as shown by transmission electron microscopy was found to be similar to the authentic SARS-CoV-2 virus particle. In a mouse trial, two intramuscular immunizations of the VLP BacMam with no adjuvant elicited spike-specific binding antibodies in both sera and bronchoalveolar lavage fluids. Importantly, BacMam VLP -vaccinated mouse sera showed neutralization activity against SARS-CoV-2 spike pseudotyped lentivirus. Our results indicated that the SARS-CoV-2 VLP BacMam stimulated spike-specific immune responses with neutralization activity.

СrAss-like phages play an important role in maintaining ecological balance in the human intestine microbiome. However, their lifestyle and genetic diversity are still insufficiently studied. In this study, a novel CrAssE-Sib phage genome belonging to the epsilon сrAss-like phage genomes was found. Detailed analysis indicated that CrAssE-Sib encodes unusual proteins – DNA primase, virion RNA polymerase, prophage antirepressor, and transcriptional repressor, as well as reverse transcriptase (RT) and receptor binding protein (RBP) that are part of diversity-generating retroelement (DGR). Comparative analysis showed that all epsilon сrAss-like phages are divided into two putative genera, which were proposed to name Epsilonunovirus and Epsilonduovirus; CrAssE-Sib belongs to the first of them. RT from CrAssE-Sib and several Epsilonunoviruses contains a specific motif in its fourth domain that was not previously found in RTs from phage and bacterial DGRs. In addition, RBP from CrAssE-Sib and all Epsilonunoviruses has a unique structure. The presence of the conservative prophage repressor and anti–repressors that belong to the lysogenic-to-lytic cycle switches indicate that CrAssE-Sib and other Epsilonunoviruses could be temperate. Epsilon сrAss-like phage substantially differ from other crAss-like phages, including zeta сrAss-like phages. This fact indicates the need to isolate these phages into a separate family.

Diamond-like carbon (DLC) films have a promising tribological application in green precision manufacturing, but their toughness represents a serious issue in the way of their application perspective. The film thickness is on the micrometer scale and makes conventional methods unsuitable for its toughness characterization. The absence of an accepted method for characterizing the DLC toughness has hindered the related research on the development of toughening methods and understanding the mechanism. This work intends to explore a relatively simple and acceptable characterization method to measure the film toughness. Moreover, toughening mechanisms of DLC films are proposed during the characterization to reveal the toughening mechanism. The toughness can be fully characterized through combining impact toughness and scratch toughness. The impact toughness can be obtained by observing the size of the indentation and the crack state around the indentation in the impact experiment. The scratch toughness could be assessed by combining the scratch morphology and Crack Propagation Resistance (CPRS). The improvement of film toughness should be carried out from two aspects: preventing microcrack initiation and suppressing crack propagation. Appropriate doping of non-carbide metal particles can effectively improve the toughness of the film, and there are seven main factors affecting the toughening of the film. Five toughening mechanisms of non-carbide metals from film preparation to test stage are revealed during the investigation of the change patterns.

The Chen circuit system, a three-dimensional autonomous system with intriguing dynamics, has gained considerable attention due to its potential applications in diverse scientific fields. In this article, a Chen circuit-like system is defined and a comprehensive dynamics has been studied. The system exhibits chaotic dynamics, limit cycles, and bifurcations, making it a captivating subject of study. By employing numerical simulations and analytical techniques, we explore the system's stability and identify critical parameter values leading to qualitative changes. Notably, we delve Hopf bifurcations, which give rise to stability changes and the emergence of limit cycles. Furthermore, we analyze the fractal dimension of the system's attractor, providing insights into its complexity and self-similarity. Through a systematic examination of the Chen circuit-like system, we deepen our understanding of its intricate dynamics and offer valuable insights into the underlying mechanisms. The findings contribute to the field of dynamical systems and hold potential implications in areas such as chaos-based secure communications, signal processing, and nonlinear control. This work serves as a valuable reference for researchers and practitioners interested in the dynamics and bifurcation analysis of nonlinear systems.

Cu-Sn shape-memory microwires were fabricated by a glass-coated melt spinning method. Effects of Sn content on the microstructure and mechanical property of microwires were investigated. The phase transforms from martensite to austenite with Sn content increasing from 14.0 atomic percent (at.%) to 16.5 at.%, and highly ordered intermetallic phase, δ, formed with higher Sn content. The fracture stress, σf, and the critical stress for martensitic transformation, σMs, increases with Sn content increasing. The mechanical property as well as superelasticity were improved greatly by high cooling rate of the glass-coated melt spinning method.

The response of structures under pulse-like ground motions is characterized by the large amount of energy input in a few cycles. Consequently, structures with insufficient strength may suffer severe damage owing to excessive deformation. In a previous paper, the energy-based prediction procedure for the peak and cumulative response of a reinforced concrete (RC) frame building with steel damper columns was proposed (Fujii and Shioda, 2023). Although this procedure was verified by comparison to the nonlinear time-history analysis (NTHA) results, the performance of the proposed procedure with pulse-like ground motion records has not been verified yet. In this study, the accuracy of the energy-based prediction procedure for an RC frame building with steel damper columns was investigated by considering pulse-like ground motions. The numerical analysis results reveal that the accuracy of the predicted peak response is satisfactory, which agrees with the results of the author’s previous study. However, the accuracy of the predicted total input energy to the building model depends on the ratio of the pulse period of the ground motion to the effective fundamental period of the building model. The reasons for this underestimation of the total input energy are discussed in this paper.

Age-related macular degeneration is a progressive retinal disease that is associated with factors such as oxidative stress, decreased phagocytic activity, and inflammation. In this study, we evaluated the protective effects of SIG-1451, a non-steroidal anti-inflammatory drug developed for treating atopic dermatitis and known to inhibit toll-like receptor 4, on light-induced photoreceptor degeneration. SIG-1451 was intraperitoneally injected into rats once a day before exposure to 1000 lx light for 24 h; one day later, optical coherence tomography showed a decrease in retinal thickness, and electroretinogram (ERG) amplitude was also found to have decreased 3 d after light exposure. Moreover, SIG-1451 protected against this decrease in retinal thickness and increase in ERG am-plitude. One day after light exposure, upregulation of inflammatory response-related genes was observed, and SIG-1451 was found to inhibit this upregulation. Iba-1, a microglial marker, was suppressed in SIG-1451-injected rats. To investigate the molecular mechanism underlying these effects, we used lipopolysaccharide (LPS)-stimulated rat immortalised Müller cells. The upregu-lation of C-C motif chemokine 2　by LPS stimulation was significantly inhibited by SIG-1451 treatment, and western blot analysis revealed a decrease in phosphorylated I-κB levels. These results indicate that SIG-1451 protects photoreceptor cells by attenuating light damage progression through inhibiting inflammatory responses.

Background: Takayasu Arteritis (TAK) increases vascular stiffness and arterial resistance. Hypertension and atherosclerosis lead to similar changes. We investigated possible differences in cardiovascular remodeling between these diseases and whether the differences are correlated with immune cell expression. Methods: Patients with active TAK arteritis were compared with age- and sex-matched hypertensive and atherosclerotic patients. In a subpopulation of TAK patients, Treg/Th17 cells were measured before (T0) and after 18 months (T18) of infliximab treatment. Echocardiogram, supraaortic Doppler ultrasound, and lymphocytogram were performed in all patients. Histological and immunohistochemical evaluation of the vessel wall was performed to compare the in vivo results. Results: TAK patients have increased aortic valve dysfunction and diastolic dysfunction. These data have been associated with uric acid levels. A significant increase in aortic stiffness was also noted and associated with peripheral T lymphocyte levels. CD3+CD4+ cell infiltrates were detected in the vessel wall samples of these patients. They had a lower mean percentage of Tregs at T0 than controls, but levels increased significantly at T18. Opposite results were found in Th17 cells. Finally, TAK patients were found to have an increased risk of atherosclerotic cardiovascular disease (ASCVD). Conclusion: Our data suggest that different pathogenic mechanisms of vessel damage, including atherosclerosis, underlie TAK patients compared with control subjects. The increased risk of ASCVD in TAK patients correlates directly with the degree of inflammatory cell infiltration in the vessel wall. Infliximab restores the normal frequency of Tregs/Th17 in TAK patients and allows a possible reduction of steroids and immunosuppressants.

Ultrasonic measurements are used in civil engineering for structural health monitoring of concrete infrastructures. The late portion of the ultrasonic wavefield, the coda, is sensitive to small changes in the elastic moduli of the material. Coda Wave Interferometry (CWI) correlates these small changes in the coda with the wavefield recorded in intact, or unperturbed, concrete specimen to reveal the amount of velocity change that occurred. CWI has the potential to detect localised damages and global velocity reductions alike. In this study, the sensitivity of CWI to different types of concrete mesostructures and their damage levels is investigated numerically. Realistic numerical concrete models of concrete specimen are generated and damage evolution is simulated using the discrete element method. In the virtual concrete lab, the simulated ultrasonic wavefield is propagated from one transducer using a realistic source signal and recorded at a second transducer. Different damage scenarios reveal a different slope in the decorrelation of waveforms with the observed reduction in velocities in the material. Finally, the impact and possible generalizations of the findings are discussed and recommendations are given for a potential application of CWI in concrete at structural scale.

The musculoskeletal system consisting of bones and muscles have been recognized as endocrine organs secreting hormones that are involved in regulating metabolic and inflammatory pathways. Obesity and type 2 diabetes (T2D) are associated with several musculoskeletal system complications. We hypothesized that an interaction exists between adipomyokines namely, irisin and METRNL, and various bone markers in individuals with obesity and T2D. A total of 228 individuals were enrolled in this study, including 124 non-diabetic and 104 T2D. A Multiplex assay was used to assess the level of various bone markers namely Osteoactivin, Syndecan, osteoprotegerin (OPG) and osteonectin/SPARC. Our data shows elevated levels of Osteoactivin, Syndecan, OPG and SPARC in T2D as compared to non-T2D individuals (p ≤ 0.05). Using Spearman’s correlation, irisin was positively correlated only with Osteoactivin and OPG (p &lt; 0.05). Similarly, a positive association was observed between METRNL and Osteoactivin (p &lt; 0.05). The strong positive association shown in our study between irisin, METRNL and various bone markers emphasises the strong interaction between these organs. This suggests that a dysregulation in the functional interaction between these molecules could play a possible role in the development of bone and muscle related complications that are associated with obesity and T2D.

Exercise affects various organs. However, its effects on nutrient digestion and absorption in the intestinal tract are not well understood. A few studies have reported that exercise training in-creases the expression of carbohydrate digestion and absorption molecules. Exercise was also shown to increase the concentration of blood glucagon like peptide-2(GLP-2), which regulates carbohydrate digestion and absorption in small intestinal epithelium. Therefore, we investigated the effects of exercise on intestinal digestion and absorption molecules and the levels of GLP-2. 6-wk-old of male mice were divided into 2 groups; sedentary (SED) and low-intensity exercise (LEx). LEx mice were required to run on a treadmill (12.5 m/min, 60 min), whereas SED mice rested. All mice were euthanized 1 h after exercise or rest and plasma, jejunum, ileum, and colon were sampled. Samples were analyzed using EIA and immunoblotting. The levels of plasma GLP-2 and the expression of the GLP-2 receptor, sucrase-isomaltase (SI), and glucose transporter (GLUT2) in the jejunum were increased in LEx group. We showed that acute low-intensity exer-cise affects the intestinal carbohydrate digestion and absorption molecules via GLP-2. Our results suggest that exercise might provide new benefits to the small intestine for people with intestinal frailty.

We present the mathematical model of cooperative functioning of unconscious and consciousness. The model is based on the theory of open quantum systems. Unconscious and consciousness are treated as bio-information systems. The latter plays the role a measurement apparatus for the former. States of both systems are represented in Hilbert spaces. Consciousness performs measurements on the states which are generated in unconscious. This process of unconscious-conscious interaction is described by the scheme of indirect measurements. This scheme is widely used in quantum information theory and it leads to the theory of quantum instruments (Davis-Lewis-Ozawa). Our approach is known as quantum-like modeling. It should be sharply distinguished from modeling of genuine quantum physical processes in biosystems, in particular, in the brain. In the quantum-like framework, the brain is a black box processing information in the accordance with the laws of quantum theory. During the last 10-15 years this framework has been actively used in cognition, psychology, decision making, social and political sciences. The quantum-like scheme of unconscious-consciousness functioning has already been explored for sensation-perception modeling.

Near-fault ground motions can cause severe damage to civil structures, including bridges. Safety assessment of these structures for near fault ground motion is usually performed through Non-Linear Dynamic Analyses, while faster methods are often used. IMPAb (Incremental Modal Pushover Analysis for Bridges) permits to investigate the seismic response of a bridge by considering the effects of higher modes, which are often relevant for bridges. In this work, IMPAb is applied to a bridge case study considering near-fault pulse-like ground motion records. The records were analyzed and selected from the European Strong Motion Database and the pulse parameters were evaluated. In the paper results from standard pushover procedures and IMPAb are compared with nonlinear Response-History Analysis (NRHA), considering also the vertical component of the motion, as benchmark solutions and incremental dynamic analysis (IDA). Results from the case study demonstrate that the vertical seismic action has a minor influence on the structural response of the bridge. Therefore IMPAb, which can be applied considering vertical motion, remains very effective conserving the original formulation of the procedure, and can be considered a well performing procedure also for near-fault events.

A novel coronavirus (2019-nCoV) that is initially found to trigger human severe respiratory illness in Wuhan City of China, 2019, has been recognized as a public health emergency of international concern. In the past two months, this deadly agent has caused 77,785 cases with 2,666 deaths via rapid person-to-person transmission and reached at least 25 countries. However, its evolutionary origin is poorly understood. Here we show integrative evidence that 2019-nCoV is a possible progenitor for SARS-CoV with bat origin. Our finding underscores the importance of tracing origin in the efficient monitoring, and effectively preventing the interspecies transmission of such emerging/re-emerging coronaviruses.

In this paper, we study the third order semilocal convergence of the Newton-like method for finding the approximate solution of nonlinear operator equations in the setting of Banach spaces. First, we discuss the convergence analysis under ω-continuity condition, which is weaker than the Lipschitz and Hölder continuity conditions. Second, we apply our approach to solve Fredholm integral equations, where the first derivative of involved operator not necessarily satisfy the Hölder and Lipschitz continuity conditions. Finally, we also prove that the R-order of the method is 2p + 1 for any p $\in$ (0,1].

Satellite-based remote sensing technologies are utilized extensively to investigate urban thermal environments under rapid urban expansion. Current MODIS data is, however, unable to adequately represent the spatially detailed information because of its relatively coarser spatial resolution, while Landsat data can’t explore temporally the refined analysis due to the low temporal resolution. In order to resolve this situation, we used MODIS and Landsat data to generate “Landsat-like” data by using the flexible spatiotemporal data fusion method (FSDAF), and then studied spatiotemporal variation of land surface temperature (LST) and its driving factors. The results showed that 1) The estimated “Landsat-like” data have high precision; 2) By comparing 2013 and 2016 datasets, LST increases ranging from 1.8°C to 4°C were measurable in areas where the impervious surface area (ISA) increased, while LST decreases ranging from -3.52°C to -0.70°C were detected in areas where ISA decreased; 3) LST has a strongly negative relationship with the Normalized Difference Vegetation Index (NDVI), and a strongly positive relationship with Normalized Difference Built Index (NDBI) in summer; and 4) LST is well correlated with Building density (BD), in a complex conic mode, and LST may increase by 0.460°C to 0.786°C when BD increases by 0.1. Our findings can provide information useful for mitigating undesirable thermal conditions and for long-term urban thermal environmental management.

In China, preschool teachers have a significant influence on the development of young children aged 3-6. It is imperative to understand their mental health and the factors associated with it to inform policies, optimize their mental well-being, and support their job performance. This study aimed to investigate the factors contributing to anxiety symptoms among preschool teachers. A sample of 393 Chinese preschool teachers (279 females, 114 males) aged 21-56 completed online questionnaires collecting their socio-demographic and work-related information and assessing anxiety symptoms, interpersonal difficulties, personality traits, perceived stress, resilience, and inner strength. Pearson correlation and multiple linear regression analyses identified significant predictors of anxiety symptoms. The prevalence of anxiety symptoms among the studied cohort was found to be 12.2%. Statistically significant factors positively correlated with anxiety symptoms included objective work-related stress (B=0.149, p<.001), interpersonal difficulties (B=0.921, p<.001), perceived stress (B=0.108, p=.001), and neuroticism (B=0.071, p=.002). The findings highlight the urgent need for measures to reduce work-related stress and anxiety. However, when negative mental health predictors were included, the effect of positive psychological factors became nullified. Positive mental health might have a moderating role in such a negative mental health outcome as anxiety. Therefore, further research is required to understand the impact of positive mental health factors more clearly.

This study explored the effectiveness of a virtual music therapy program, based on positive psychotherapy principles, for college students during the COVID-19 pandemic. Twenty-four undergraduate students with partial PTSD were initially assigned to either an experimental group or a control group, with 11 participants in each group by the study's end. The experimental group underwent 15 video sessions of the therapy program, completing one session per weekday over three weeks. The program involved worksheets targeting goals aligned with positive psychology, such as positive affect, life meaning, personal strengths, gratitude, hope, and happiness. Activities included writing music autobiographies, creating and analyzing song lyrics, and exploring various music pieces. The effectiveness of the intervention was measured using the 21-item Depression Anxiety Stress Scale and the Korean Version of Positive Psychological Capital (K-PPC) before, immediately after, and three weeks post-program. The experimental group showed significant improvements in stress, anxiety, depression, self-efficacy, resilience, and the K-PPC total score compared to the control group. These improvements were maintained at the three-week follow-up. The findings suggest that positive psychology-based virtual music therapy can significantly enhance the mental health of highly stressed college students, especially during challenging times like the COVID-19 pandemic.

The study looks at how joining live video chats with native English speakers on TikTok helps people who are learning English feel more ready to talk in English and less nervous about it. This study looks at EFL students who join TikTok live sessions. The researcher wants to understand how confident and nervous the students feel when they communicate. He uses qualitative research methods to do this. The study shows that using TikTok in a fun and calming way could help people learn a new language and reduce feelings of worry. This is helpful for teachers and language experts who want to use social media to help people learn languages.

Objective: The COVID-19 pandemic inferred on neuro-oncological patients (PTS) and the caregivers regarding tumor care and emotional functioning. This study aimed to understand how COVID-19 affects their psychological state and relations between PTS and health personnel in neuro-oncology. Methods: A cross-sectional study on neuro-oncological PTS and their caregivers. Results: A total of 162 PTS and 66 caregivers completed the questionnaire. The 37.5% of PTS perceived greater risk of contracting the COVID-19 compared to the general population. On the 0-10 scale, PTS tumor-related anxiety score was 5.8 and COVID-related 4.6. The caregivers reported 7.7 and 5.5 respectively. The QoL was described at least as good in 75% of both PTS and caregivers; the caregivers’ care burden increased in 22.7% during the pandemic, with no correlation with QoL. Future perception often changed both in PTS and in the caregivers. Cancer treatment schedule was changed in 18.5%, including for PTS decision. However, the 93.5% of PTS was satisfied with the overall care. Conclusion: A considerable proportion of PTS and caregivers still perceived the tumor disease as more burdensome than the pandemic, and perceived their future as more uncertain. Such data rinforce the need to build a proficient alliance between PTS and health personnel.

Globally, workplace stress and anxiety are at an all-time high, with 42% of employees experiencing daily work-related stress and anxiety. Drawing from workplace anxiety (WA) theory (Cheng &amp; McCarthy, 2018), we advance a model that considers four job demands – role ambiguity, work overload, job insecurity, and work-home conflict – as sources of daily WA, and in turn the downstream effects of WA on psychological capital (PsyCap). Our model posits gender as a moderator of the association between job demands and WA, and digital technology characteristics as moderators of the association between WA and PsyCap. We tested our predictions on a sample of 162 South African employees. Consistent with our predictions, we found positive effects of job demands on WA, with the relationship being stronger for females. Contrary to expectations, we found positive effects of WA on PsyCap, suggesting an adaptive function of WA. Perceived ease of use of digital technology moderated the association between WA and PsyCap, such that the association was strong at higher levels of perceived ease of use. This research advances our understanding of the sources of WA, the adaptive function of WA, and predictors of PsyCap. Broadly, our study adds to understanding emotions’ impact on workplace behavior.

There is an anecdotal impression that teenage patients report exaggerated postoperative pain scores that do not correlate with their actual level of pain. Nurse and parental perception of teenagers' pain can be complemented by knowledge of patient pain behavior, pain catastrophizing thoughts, anxiety, and mood level. Two hundred two patients completed the study: 56.4% female, 89.6% White, 5.4% Black, and 5% other race. Patient ages ranged from 11 to 17 years (mean = 13.8, SD = 1.9). The patient, the parent, and the nurse completed multiple questionnaires on day one after laparoscopic surgery to assess patient pain. Teenagers and parents (r=0.56) have a high level of agreement, and teenagers and nurses (r=0.47) have a moderate level of agreement on pain scores (p &lt;0.05). The correlation between patient APBQ (Adolescent Pain Behavior Questionnaire) and teenager VAS (Visual Analog Scale ) and between nurse APBQ and teenager VAS, while statistically significant (p &lt; 0.05), is weaker (r range = 0.14-0.17). There is a moderate correlation between teenagers' pain scores and their psychological assessments of anxiety, catastrophic thoughts, and mood (r range= 0.26 – 0.39; p &lt;0.05). A multi-modal evaluation of postoperative pain can be more informative than only assessing self-reported pain scores.

Background and Objectives: Rheumatic diseases often exhibit a complex pattern of comorbidities, including the increased occurrence of emotional disorders like anxiety and depression, which are closely related to the presence of chronic pain. Therefore, a multimodal approach is necessary for treatment, targeting both the physical and psychological functioning. Due to the increased burden within the healthcare context that emerged during the post-pandemic period, the need to adjust the content and length of psychological interventions became ubiquitous. In this way, the main objective of this study was to investigate the efficiency of a single-session, process-based psychological intervention for patients with rheumatic conditions and emotional comorbidities in a naturalistic, in-patient setting. Materials and Methods: After the screening, a total of 31 participants (Mage = 58.9, SD = 12.03) completed the single session intervention. The therapeutic protocol relied on a process-based cognitive-behavioural therapy framework aiming to improve cognitive, emotional and behavioural functioning. Assessments were conducted prior to the intervention, post-intervention and one month following the hospitalization. Results: Immediately after the intervention, significant reductions in dysfunctional cognitive and emotional processes, along with the improvement of behavioural strategies were observed. At the one-month telephonic evaluation, participants reported decreased pain, state anxiety and state depression levels. Conclusions: The single-session, process-based approach represents a promising intervention in healthcare contexts, targeting important psychopathological mechanisms in patients with rheumatic conditions. Future studies could clarify the extent to which these outcomes persist over time and their specific associations with anxiety and depressive symptoms, by using more controlled and rigorous trial designs.

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.

Songorine (SON) is a diterpenoid alkaloid from Aconitum plants. Preparations of Aconitum roots have been employed in traditional oriental herbal medicine, however, their mechanisms of action are still unclear. Since GABA-receptors are possible brain targets of SON, we investigated which subtypes of GABA-receptors contribute to the effects of SON, and how SON affects anxiety-like trait behavior and psychomotor cognitive performance of rats. First, we investigated the effects of microiontophoretically applied SON alone and combined with GABA-receptor agents picrotoxin and saclofen on neuronal firing activity in various brain areas. Next, putative anxiolytic effects of SON (1.0-3.0 mg/kg) were tested against the GABA-receptor positive allosteric modulator refer-ence compound diazepam (1.0-5.0 mg/kg) in the elevated zero maze (EOM). Furthermore, basic cognitive effects were assessed in a rodent version of the psychomotor vigilance task (PVT). Local application of SON predominantly inhibited the firing activity of neurons. This inhibitory effect of SON was successfully blocked by GABA(A)-receptor antagonist picrotoxin but not by GABA(B)-receptor antagonist saclofen. Similar to GABA(A)-receptor positive allosteric modulator diazepam, SON increased the time spent by animals in the open quadrants of the EOM without any signs of adverse psychomotor and cognitive effects observed in the PVT. We showed that, under in vivo conditions SON acts as a potent GABA(A)-receptor agonist and effectively decreases anxiety without observable side effects. The present findings facilitate the deeper understanding of the mechanism of action and the widespread pharmacological use of diterpene alkaloids in various CNS indications.

Alcohol use disorder (AUD) represents major public and socioeconomic issues. Alcohol exerts its phar-macological effects by altering different neurotransmitter systems, such as g-aminobutyric acid (GABA), glutamate, opioids, etc. Recent evidence suggests that the dynorphin (DYN)/kappa opioid receptor (KOR) system mediates the negative affective states associated with alcohol withdrawal. This system is also in-volved in stress-mediated alcohol intake in alcohol-dependent subjects. The DYN/KOR system probably exerts its action in the central nucleus of the amygdala (CeA) to mediate the negative affective states as-sociated with alcohol withdrawal. This article aims to review the current literature regarding the role of the DYN/KOR system in the actions of alcohol. We first review the literature regarding the effect of alcohol on the level of the peptide and its receptor, and the role of the endogenous DYN/KOR system in alcohol reward and negative affective states associated with alcohol withdrawal is then discussed. We also review the literature regarding the effects of KOR ligands on these processes.

Background Research on the mental health of students in health disciplines mainly focuses on psychological distress and nursing and medical students. This study aimed to investigate the psychological well-being and distress and related factors among undergraduate students training in eight different health-related tracks in Geneva, Switzerland. Methods This cross-sectional study used established self-filled scales for anxiety, depression, stress, psychological well-being, and study satisfaction. Descriptive statistics and hierarchical regression analyses were applied. Results In October 2019, out of 2835 invited students, 915 (32%) completed the survey. Lower academic satisfaction scores were strongly associated with depression (β=-.26, p<.001), anxiety (β=-.27, p<.001), and stress (β=-.70, p<.001), while higher scores with psychological well-being (β=.70, p<.001). Being female was strongly associated with anxiety and stress but not with depression or psychological well-being. Increased age was associated with enhanced psychological well-being. The nature of the academic training had a lesser impact on mental health and the academic year none. Conclusion Academic satisfaction strongly predicts depression, anxiety, stress, and psychological well-being. Training institutions should address the underlying factors that can improve students’ satisfaction with their studies while ensuring that they have access to psychosocial services that help them cope with mental distress and enhance their psychological well-being.

The COVID-19 appears as a catastrophic health risk with psychological, emotional, social and relational implications. From the early stages of the virus spread, the elderly population was identified as the most vulnerable and the health authorities have rightly focused on such frailest population. Conversely, less attention was paid to emotional and psychological dimension of children and adolescents. Actually, they were less at risk quoad vitam or quoad valetudinem, nevertheless they had to face a reality of anxiety, fears and uncertainties. The current study investigated state anxiety and emotion awareness in a healthy sample of older adolescents, 84 females and 64 males, aged 17 to 19, during the pandemic lockdown, using Self-rating Anxiety Scale and the Italian Emotion Awareness Questionnaire. An unexpected anxious phenomenology, impacting the anxiety ideo-affective domain, was found, while the somatic symptomatology appeared to be less severe. The highest anxiety symptom were the breathing difficulties. These findings supported the hypothesis that the COVID-19 pandemic may be a risk condition for an increased state anxiety in older adolescents and suggest the need to provide 1. an effective, empathic communication system with the direct participation of older adolescents, 2. a psychological counseling service for stress management of adolescents.

Nowadays, mindfulness-based interventions (MBI) have experimented a remarkable development of studies among childhood and adolescent interventions. For this reason, dispositional mindfulness (DM) measures for children and adolescents have been developed to determine the effectiveness of MBI at this age stage. However, little is known about how key elements of DM (f. e., cognitive de/fusion or experiential avoidance that both conform psychological inflexibility) are involved in the mechanisms of the children and adolescents’ mental health outcomes. This research examined the mediating effect of cognitive fusion between DM and anxiety and other negative emotional states in a sample of 318 Spanish primary-school students (aged between 8 and 16 years, M=11.24, SD=2.19, 50.8% males). Participants completed the AFQ-Y, which is a measure of psychological inflexibility that encompasses cognitive defusion and experiential avoidance; CAMM (DM for children and adolescents), PANAS-N (positive and negative affect measure for children, the Spanish version of PANASC), and STAIC (an anxiety measure for children). The study accomplished ethical standards. As MBI relevant literature has suggested, cognitive defusion was a significant mediator between DM and symptoms of both negative emotions and anxiety in children and adolescents. However, experiential avoidance did not show any significant mediating relationship. Probably, it is needed improvement of the assessment of experiential avoidance. MBI programs for children and adolescents may include more activities for reducing the effects of the cognitive defusion on their emotional distress.

There is increasing evidence and recognition that Lyme borreliosis, and other associated tick-borne diseases (LB/TBD) cause mental symptoms. Data was drawn from databases, search engines and clinical experience to review current information on LB/TBD. LB/TBD infections cause immune and metabolic effects that result in a gradually developing spectrum of neuropsychiatric symptoms, usually presenting with significant comorbidity and may include developmental disorders, autism spectrum disorders, schizoaffective disorders, bipolar disorder, depression, anxiety disorders (panic disorder, social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder, intrusive symptoms), eating disorders, decreased libido, sleep disorders, addiction, opioid addiction, cognitive impairments, dementia, seizure disorders, suicide, violence, anhedonia, depersonalization, dissociative episodes, derealization and other impairments. Screening assessment followed by a comprehensive psychiatric clinical exam relevant to patient’s complaints and findings with a thorough history, mental status exam, review of systems, neurological exam, physical exam, a knowledgeable interpretation of laboratory findings, pattern recognition and clinical judgment facilitate diagnosis. Psychotropics and antibiotics may help improve functioning and prevent further disease progression. Awareness of the association between LB/TBD and neuropsychiatric impairments and studies of their prevalence in neuropsychiatric conditions can improve understanding of the causes of mental illness and violence and result in more effective prevention, diagnosis and treatment.

Strawberry fruit is highly appreciated worldwide for its organoleptic and healthy properties. However, this plant is attacked by many pathogenic fungi, which significantly affect fruit production and quality at pre- and post-harvest stages, making chemical applications the most effective but undesirable strategy to control diseases, so far. Alternatively, genetic manipulation employing plant key genes involved in defense, such as members of the NPR-like gene family, has been successful in many crops to improve resistance. The identification and use of the endogenous counterpart genes in the plant of interest (as it is the case of strawberry) is desirable as it would increase the favorable outcome and requires prior knowledge of their defense related function. Using RNAi technology in strawberry, we show that transient silencing of Fragaria ananassa NPR3 members in fruit significantly reduces tissue damage after Colletotrichum acutatum infection whereas the ectopic expression of either FaNPR3.1 or FaNPR3.2 does not have an apparent effect. Furthermore, the ectopic expression of FaNPR3.2 in Arabidopsis thaliana double mutant npr3npr4 reverts the disease resistance phenotype to Pseudomonas syringe to wild type levels. Therefore, our results reveal that members of the strawberry FaNPR3 clade negatively regulate the defense response to pathogens, as do their Arabidopsis AtNPR3/AtNPR4 orthologs. Also, we provide evidence that FaNPR3 members act in strawberry (F. ananassa) as positive regulators of WRKY genes, FaWRKY19 and FaWRKY24, and that in Arabidopsis, FaNPR3.2 negatively regulates its orthologous genes AtNPR3/AtNPR4. We report for the first time the functional characterization of FaNPR3 members in F. ananassa which provides a relevant molecular basis for the improvement of resistance in this species through new breeding technologies.

Many protein expression systems are primary utilised to produce a single, specific recombinant protein. In contrast, most biological processes such as virus assembly rely upon a complex of several interacting proteins rather than the activity of a sole protein. The high complexity of the baculovirus genome, coupled with a multiphase replication cycle incorporating distinct transcriptional steps, made it the ideal system to manipulate for high-level expression of a single or co-expression of multiple foreign proteins within a single cell. We have developed and utilised a series of recombinant baculovirus systems to unravel the sequential assembly process of a complex non-enveloped model virus, Bluetongue virus (BTV). The high protein yields expressed by the baculovirus system not only facilitated structure-function analysis of each viral proteins but were also advantageous to crystallography studies and supported the first atomic level resolution of a recombinant viral protein, the major BTV capsid protein. Further, the formation of recombinant double-shelled virus-like particles (VLPs) provided insights into the structure-function relationships among the four major structural proteins of the BTV whilst also representing a potential candidate for a viral vaccine. The baculovirus multi-gene expression system facilitated the study of structurally complex viruses (both non-enveloped and enveloped viruses) and heralded in a new generation of viral vaccines.

In this work, we incorporate a thixotropic-viscoelastic model into the widely used Computational Fluid Dynamics (CFD) software OpenFOAM, along with the rheoTool library. The model we implement is known as the Modified-Bautista-Manero (MBM), and effectively describes the rheological behavior of worm-like micellar solutions in extensional flows. We provide a detailed explanation of the numerical implementation of the model, specifically using the log-conformation tensor approach. Unlike previous works focused on this kind of fluids, we simulate inertial flows while considering convective terms in the governing equations, thus obtaining a more realistic behavior on the calculated results. The MBM model implementation is validated through numerical simulations on two different industrial-relevant geometries: the planar 4:1 contraction and the 4:1:4 contraction-expansion configurations. Furthermore, we investigate the influence of inertial, viscoelastic, and thixotropic effects on various flow field variables. These variables include velocity, viscosity, normal stresses, and corner vortex size. Our analysis encompasses both transient and steady solutions of corner vortexes across a range of Deborah and Reynolds numbers. Our results are also directly compared with simulations obtained using the non-thixotropic rubber network-based exponential Phan-Thien-Tanner (EPTT) model. From our planar 4:1 contraction results, we found that vortex-enhancement is seen when high elasticity is coupled with quick structural reformation and very low inertial effects. From our planar 4:1:4 contraction-expansion simulations, we show that an increase in inertia leads both to vortex-inhibition in the upstream channel and slight vortex-enhancement in the downstream channel. Lastly, we show the strong effect of the convection of fluidity into the fluidity profiles and into the upstream/downstream corner vortex sizes.

Biomimetics, which are similar to natural compounds that play an important role in the metabolism, manifestation of functional activity and reproduction of various fungi, have a pronounced attrac-tion in the current search for new effective antifungals. Actual trends in the development of this area of research indicate that unnatural amino acids can be used as such biomimetics, including those containing halogen atoms; compounds similar to nitrogenous bases embedded in the nucleic acids synthesized by fungi; peptides imitating fungal analogues; molecules similar to natural sub-strates of numerous fungal enzymes and Quorum Sensing signaling molecules of fungi and yeast; etc. Most part of the review is devoted to the analysis of semi-synthetic and synthetic antifungal peptides and their targets of action. This review is aimed at combining and systematizing the cur-rent scientific information accumulating in this area of research, developing various antifungals with an assessment of the effectiveness of the created biomimetics and the possibility of combining them with other antimicrobial substances to reduce cell resistance and improve antifungal effects.

Neurodegeneration is becoming one of the leading causes of death worldwide as the population expands and grows older. There is a growing desire to understand the mechanisms behind prion proteins as well as the prion-like proteins that make up neurodegenerative diseases (NDs) including Alzheimer’s Disease (AD). Both amyloid β (Aβ) and hyperphosphorylated tau (p-tau) proteins behave in ways similar to that of the infectious form of the prion protein, PrPSc, such as aggregating, seeding, and replicating under not yet fully understood mechanisms, thus the designation of prion-like. This review aims to highlight the shared mechanisms between prion-like proteins and prion proteins in the structural variations associated with aggregation and disease development. These mechanisms are largely focusing on the dysregulation of protein homeostasis, self-replication, and protein aggregation, and how this knowledge could contribute to diagnoses and treatments for the given NDs.

Background: Obtaining adipose-derived stem cells is limited by its capacity to differentiate. Stimulation by platelet-rich fibrin appears to have the beneficial effects to accelerate differentiation. Objective: To obtain immunohistochemistry evidence of platelet-rich fibrin to accelerate differentiation of adipose-derived stem cells. Methods: We used post-test only controlled-group design. Adipose-derived stem cells were isolated and cultured until 4 passages in α-MEM culture medium. Results: GATA-4 expression increased in platelet-rich fibrin group compared with control group (68.20±6.82 vs 58.15±1.23 counts; p<0.05; 68.20±6.82 vs 52.96±2.02 counts; p<0.05). Troponin expression also increased in platelet-rich fibrin group (50.66±7.2 vs 10.73±2.39 counts; p<0.05; 50.66±7.2 vs 26.00±0.4 counts; p<0.05). Conclusion: There is an immunohistochemistry benefit of platelet-rich fibrin to accelerate differentiation of adipose-derived stem cells into cardiomyocyte-like cells.

Filamentous manganese (Mn) oxide particles, which occur in the suboxic zone of stratified waterbodies, are important drivers of diverse elemental cycles. Although these particles are considered to be bacteriogenic, the environmental factor responsible for their formation has not been identified. Based on this study of laboratory cultures of a model Mn(II)-oxidizing bacterium, the supply of algal extracellular polymeric substances (EPS) was shown to stimulate Mn(II) oxidation and thus the production of filamentous Mn oxide particles. This observation was consistent with results obtained for naturally occurring particles collected from a near-bottom layer (depth of ~90 m) in the northern basin of Lake Biwa, Japan, that is, most Mn particles resembling delta-MnO2 were associated with an EPS-like gelatinous matrix, which contained dead algal cells and was lectin-stainable. In the lake water column, EPS produced by photosynthesis sank to the bottom layer. The analysis of the quality of water samples, which have been collected from the study site for 18 years, reveals that the annual average total phytoplankton biovolume in the surface layer correlates with the density of filamentous Mn particles in the near-bottom layer. Among different phytoplankton species, green algae appeared to be the key species. The results of this study suggest that algal EPS production induces the formation of filamentous Mn oxide particles in the near-bottom layer of the northern basin of Lake Biwa.

RNA interference is a highly conserved process in which non-coding small RNAs (sRNA) modulate gene expression at the post-transcriptional level influencing plant growth and development. Dicer-like (DCL), Argonaute (AGO) and RNA-dependent RNA polymerase (RDR) are the core elements involved in gene silencing and their gene families have been explored in many plants. However, these genes and their response to abiotic stresses have not yet been well in wheat. In this study, 82 AGO, 31 DCL, and 31 RDR genes were identified and phylogenetic analysis of these proteins showed that clustered into ten, four and four clades respectively. RNA-seq analysis revealed constitutive expression of AGO1, AGO9, and DCL2 family expression analysis in tissues under normal and stress conditions, whereas RDR1 which is known to engage in siRNA biogenesis showed higher expression levels in wheat leaf tissues. Our findings build the foundation for comparative genomics analyses of RNA silencing elements in cereal crops, as well as new insights into the functional complexity of RNA silencing in wheat stress responses, which is critical for understanding the processes underlying wheat stress responses.

Understanding the complex interactions between metabolism and the immune system (“meta-flammation”) is crucial for the identification of key immunomodulatory factors as potential therapeutic targets in obesity and in cardiovascular diseases. Cathelicidin antimicrobial peptide (CAMP) is an important factor of innate immunity and is expressed in adipocytes. CAMP therefore might play a role as an adipokine in metaflammation and adipose inflammation. Toll-like receptor (TLR) 9 is another component of the innate immune system that is expressed and functionally active in adipocytes. The aim of the present study was to investigate the impact of TLR9 signaling on CAMP expression in adipocytes and in adipose tissue. CAMP gene expression in murine 3T3-L1 and human SGBS adipocytes and in murine and human adipose tissues was quantified by real-time PCR. TLR9 knockdown was applied in murine 3T3-L1 adipocytes via siRNA transfection. Adipocyte inflammation was induced in vitro by TNFα stimulation. Serum CAMP concentrations in TLR9 knockout (KO) and in wildtype mice were quantified by ELISA. CAMP gene expression was considerably increased in 3T3-L1 adipocytes during differentiation. TNFα significantly induced CAMP gene expression in mature adipocytes, which was antagonized by inhibitors of NF-κB and PI3K signaling. Cell-free nucleic acids (cfDNA) as endogenous TLR9 ligand significantly impaired CAMP gene expression, whereas synthetic agonistic and antagonistic TLR9 ligands had no effect. Cellular TLR9 knockdown reduced adipocyte CAMP gene expression in vitro and male TLR9 knockout mice exhibited lower systemic CAMP concentrations than wildtype mice. CAMP and TLR9 gene expression were correlated positively in murine and human subcutaneous but not in intraabdominal/visceral adipose tissues. These findings suggest a regulatory role of TRL9 in adipocytic CAMP expression as a novel putative molecular mechanism in adipose tissue innate immunity.

Spiral steroids (SS) are a newly discovered type of steroid. Originally, they were described as cardiotonic glycosides because they cross-reacted with digoxin-specific antibodies (Digoxin-Like-Materials-DLM). SS differ from the classical steroids in several ways: [a] they are steroid phosphodiester conjugates and displace digoxin from digoxin-specific antibodies, [b] in contrast to all other steroids, cholesterol is not a precursor, [c] SS have more than 21 carbon atoms; the extra atoms form a 5th ring which includes a lactone, [d] SS bind to NaK-ATPase in membranes rather than receptors in the nucleus. SS have been identified by HPLC- mass spectroscopy in extracts from mammals, birds, and oysters but were not detected in plant extracts. Overall, SS seem to be key components in regulating potassium electrolytes during pregnancy and its related diseases – specifically pre-eclampsia and necrotizing enterocolitis.

This paper attempts to describe the large-scale (solar system-like, astronomical-scale) systems of the known world using the physical models and mathematical tools of relativistic quantum mechanics. The value of H_x can be introduced and approximated as an analogue of the constant ℏ. Based on the quantum mechanical approach, the proper time scale of the solar system can be determined.

Background: There is several challenges to solve irreversible loss of cardiomyocytes due to myocardial infarction. Cell therapy is believed as an ideal treatment for cardiac regeneration in the infarct area. Obtaining adipose-derived stem cells increases seems to be promising, however it is limited by the capacity to differentiate. Stimulation by injectable platelet-rich fibrin appears to have the beneficial effects to accelerate cardiomyocyte-like cells differentiation. Objective: To analyse the benefit of injectable platelet-rich fibrin to accelerate differentiation of adipose-derived mesenchymal stem cells into cardiomyocyte-like cells. Methods: This study is a true experimental randomized post-test design study. Adipose-derived mesenchymal stem cells were isolated from adipose tissues and cultured until 4 passages. The characteristics of adipose-derived mesenchymal stem cells were measured by the expression of CD 34-, CD 45-, and CD 105+ using flowcytometry. The samples were divided into 3 groups, i.e. negative control (α-MEM), positive control (differentiation medium) and treatment group (platelet-rich fibrin). The assessment of GATA-4 marker expression was conducted using flowcytometry on the fifth day and troponin was conducted using immunocytochemistry on the tenth day to determine the differentiation to cardiomyocyte. Data analysis was conducted using T-test and One-Way ANOVA on normally distributed data determined through Shapiro-Wilk test. Results: Flowcytometry on GATA-4 expression revealed significant difference on addition of platelet-rich fibrin compared with negative and positive controls (68.20 ± 6.82 vs 58.15 ± 1.23; p<0.05; 68.20 ± 6.82 vs 52.96 ± 2.02; p<0.05). This was supported by the results of immunocytochemistry on troponin expression which revealed significant difference between platelet-rich fibrin group compared with negative and positive controls (50.66 ± 7.2 vs 10.73 ± 2.39; p<0.05; 50.66 ± 7.2 vs 26.00 ± 0.4; p<0.05). Conclusion: Injectable platelet-rich fibrin has beneficial effect to accelerate differentiation of adipose-derived mesenchymal stem cells into cardiomyocyte-like cells.

There is an overarching need to find alternative treatment options for malaria and this quest is more pressing in current times due to the morbidity and mortality data arising from most endemic countries and partially owing to the fact that the SARS-Cov-2 pandemic has diverted much public health attention. Additionally, the therapeutic options available for malaria has been severely threatened with the emergence of resistance to almost all existing drugs by the human malaria parasite. The Artemisinin Combination Therapies (ACTs) which hitherto have been the mainstay for malaria have encountered resistance in South East Asia, a notorious ground zero for the emergence of antimalarial drug resistance. This review analyses few key druggable targets of the parasite and the potential to leverage strategic inhibitors to mitigate the scourge of malaria by providing a concise assessment of the essential proteins of the malaria parasite that could serve as targets. Furthermore, this work provides a summary of the advances made in malaria parasite biology and the potential to leverage such findings for antimalarial drug production.

Poly(2-methoxyethyl acrylate) (PMEA) and poly(ethylene oxide) (PEO) have protein-antifouling properties and blood compatibility. ABA triblock copolymers (PMEAn-PEO11340-PMEAn (MEOMn)) were prepared using single-electron transfer-living radical polymerization (SET-LRP) using a bi-functional PEO macroinitiator. Two types of MEOMn composed of PMEA blocks with a degree of polymerization (DP = n) of 85 and 777 were prepared using the same PEO macroinitiator. MEOMn formed flower micelles with a hydrophobic PMEA (A) core and hydrophilic PEO (B) loop shells in diluted water with a similar appearance to petals. The hydrodynamic radii of MEOM85 and MEOM777 were 151 and 108 nm, respectively. The PMEA block with a large DP formed a tightly packed core. The aggregation number (Nagg) of the PMEA block in a single flower micelle for MEOM85 and MEOM777 was 156 and 164, respectively, which were estimated using a light scat-tering technique. The critical micelle concentrations (CMCs) for MEOM85 and MEOM777 were 0.01 and 0.002 g/L, respectively, as determined by the light scattering intensity and fluorescence probe techniques. The size, Nagg, and CMC for MEOM85 and MEOM777 were almost the same inde-pendent of hydrophobic DP of the PMEA block.

Leucokinins (LKs) constitute a family of neuropeptides identified in numerous insects and many other invertebrates. The LKs act on G-protein coupled receptors that display only distant relations to other known receptors. In adult Drosophila, 26 neurons/neurosecretory cells of three main types express LK. The four brain interneurons are of two types, and these are implicated in several important functions in the fly’s behavior and physiology, including feeding, sleep-metabolism interactions, state-dependent memory formation, as well as modulation of gustatory sensitivity and nociception. The 22 neurosecretory cells (ABLKs) of the abdominal neuromeres coexpress LK and a diuretic hormone (DH44), and together these regulate water and ion homeostasis and associated stress, as well as food intake. In Drosophila larvae, LK neurons modulate locomotion, escape responses, and aspects of ecdysis behavior. A set of lateral neurosecretory cells, ALKs, in the brain express LK in larvae, but inconsistently so in adults. These ALKs coexpress three other neuropeptides and regulate water and ion homeostasis, feeding and drinking, but the specific role of LK is not yet known. This review summarizes Drosophila data on embryonic lineages of LK neurons, functional roles of individual LK neuron types, interactions with other peptidergic systems, and orchestrating functions of LK.

We continue to analyze basic constraints on human's decision making from the viewpoint of quantum measurement theory (QMT). As has been found, the conventional QMT based on the projection postulate cannot account for combination of the question order effect (QOE) and the response replicability effect (RRE). This was an alarm signal for quantum-like modeling of decision making. Recently, it was shown that this objection to quantum-like modeling can be removed on the basis of the general QMT based on quantum instruments. In the present paper we analyse the problem of combination of QOE, RRE, and the famous QQ-equality (QQE). This equality was derived by Busemeyer and Wang and it was shown (in the joint paper with Solloway and Shiffrin) that statistical data from many social opinion polls satisfies it. Now, we construct quantum instruments satisfying QOE, RRE, and QQE. The general features of our approach are formalized with postulates which generalize {\it Wang-Busemeyer} postulates for quantum-like modeling of decision making. Moreover, we show that our model closely reproduces the statistics of the famous Clinton-Gore Poll data with a prior belief state independent of the question order. This model successfully removes the order effect from the data to determine the genuine distribution of the opinions in the Poll. The paper also provides a psychologist-friendly introduction to the theory of quantum instruments - the most general mathematical framework for quantum measurements. We hope that this theory will attract attention of psychologists and will stimulate further applications.

The ubiquitin-specific protease 2 (USP) belongs to the family of deubiquitinases and plays a critical role in tumors cells’ survival and therefore signifies an important therapeutic target. Previous studies have indicated promising efficacies of potent human USP2 inhibitors including, thiopurine analogues against SARS-CoV papain-like proteases (PLpro). The PLpro have significant functional implications in the innate immune response during SARS-CoV-2 infection and considered an important antiviral target. Both proteases share strikingly similar USP fold with right-handed thumb–palm–fingers structural scaffold and conserved catalytic triad Cys-His-Asp/Asn. In this urgency situation of COVID-19 outbreak, there is a lack of in-vitro facilities readily available to test SARS-CoV-2 inhibitors in whole-cell assays. Therefore, we adopted an alternate route to identify potential USP2 inhibitor through integrated structure-based virtual screening efforts. After a subsequent virtual screening protocol, the best compounds were selected and tested. The compound Z93 showed significant IC₅₀ value against Jurkat (9.67 µM) and MOTL-4 cells (11.8 µM). The binding mode of Z93 was extensively analyzed through molecular docking, followed by MD simulations, and molecular interactions were compared with SARS-CoV-2. The relative binding poses of Z93 fitted well in the binding site of both proteases and showed consensus π-π stacking and H-bond interactions with histidine and aspartate/asparagine residues of the catalytic triad. These results led us to speculate that compound Z93 might be the first potential chemical lead against SARS-CoV-2 PLpro, which warrants in-vitro evaluations.

Previous research has already examined the relationship between Future Anxiety, a construct recently introduced in Italy, and mental health in young adults, although possible mediating variables in this relationship have so far never been investigated. The present study attempts to fill this gap by exploring the incidence of Future Anxiety on psychological distress in a group of 302 young Italian adults (18 - 30 years; M = 21.9; SD = 2.6), presenting and evaluating the simultaneous mediating effect of Intolerance of Uncertainty and Non-Pathological Worry.Findings highlighted how Future Anxiety had a positive and significant direct effect on Stress and Depression, but not on Anxiety. In the three serial mediation models proposed, Intolerance of Uncertainty and Non-Pathological Worry mediated the relationship between Future Anxiety and mental health outcomes. The results also confirmed the hypothesized serial mediation effect by highlighting how young adults with greater Future Anxiety experienced more Intolerance of Uncertainty, which positively affected Non-Pathological Worry levels and, in turn, exacerbated psychological distress. Finally, results indicated that female participants experienced more Stress, Anxiety, and Depression in relation to Future Anxiety compared to males. Starting from the review of main references on this subject, the results discussed provide new insights for understanding youth psychological distress. Finally, practical implications for the design of supportive interventions for this study’s target group are proposed.

Ecological changes evoke many felt losses and types of grief. These affect sustainability efforts in profound ways. Scholarship on the topic is growing, but the relationship between general grief research and ecological grief has received surprisingly little attention. This interdisciplinary article applies theories of grief, loss, and bereavement to ecological grief. Special attention is given to research about “non-death loss” and other broad frameworks about grief. Dynamics related to both local and global ecological grief are discussed. Kinds of potential losses arising out of ecological issues are clarified with the frameworks of tangible/intangible loss, ambiguous loss, nonfinite loss, and shattered assumptions. Various possible types of ecological grief are illuminated by discussing the frameworks of chronic sorrow and anticipatory grief/mourning. Earlier scholarship about disenfranchised ecological grief is augmented by further distinctions about various forms it may take. The difficulties in defining complicated or prolonged grief in ecological context are discussed, and four types of “complicated ecological grief” are explored. Based on the findings, three special forms of ecological loss and grief are named and discussed: transitional loss and grief, lifeworld loss, and shattered dreams. The implications of the results for ecological grief scholarship, counselling and coping are briefly discussed. The results can be used by psychological and healthcare professionals and researchers, but also by members of the public who wish to reflect on their eco-emotions.

The main objective of this paper is to assess pro-environmental behavior, climate change perception, anxiety, hope and despair in different political orientations. Specific aims included to validate all the instruments; to assess whether the factor structure of the scales were valid across political orientations; to evaluate their reliability; to assess differences concerning age, gender and political orientation; to know the variables that explain pro-environment behavior; and to evaluate the moderating role of climate change perception, despair and hope in the relationship between climate change anxiety and pro-environmental behavior. Confirmatory factor analysis (CFAs), multi-group CFAs (to measurement invariance), multiple linear regressions and moderations were performed. Results showed that pro-environment behavior and climate change hope achieved the four levels of invariance across different political orientations; climate change anxiety achieved the three first levels of invariance; climate change perception and climate change despair achieved configural invariance. Climate change anxiety personal experience, climate change perception total, reality and consequences present higher values in left political orientation that in right or center. Climate change anxiety variables contribute most to explaining pro-environmental behaviors. Hope, despair and climate change perception consequences moderate de relationship between climate change anxiety and pro-environment behavior. These results open up new avenues of investigation, namely, to understand why high levels of anxiety lead to more pro-environment al behaviors.

The prolonged lockdown imposed to contain the COVID-19 pandemic prevented many people from direct contact with nature and greenspaces, raising alarms for a possible worsening of mental health. This study investigates the effectiveness of a simple and affordable remedy for improving psychological well-being, based on audio-visual stimuli brought by a short computer video showing forest environments, with an urban video as a control. Randomly selected participants were assigned the forest or urban video, to look at and listen early in the morning, and filled questionnaires. In particular, the State-Trait Anxiety Inventory (STAI) Form Y, collected in baseline condition and at the end of the study, and the Part II of the Sheehan Patient Rated Anxiety Scale (SPRAS), collected every day immediately before and after watching the video. The virtual exposure to forest environments showed effective to reduce perceived anxiety levels in in people forced by lockdown in limited spaces and environmental deprivation. Although significant, the effects were observed only in the short term, highlighting the limitation of the virtual experiences. The reported effects might also represent a benchmark to disentangle the determinants of health effects due to real forest experiences, for example, the inhalation of biogenic volatile organic compounds (BVOC).

The aim of this article has been to evaluate the impact of a physical-sport education programme, based on the pedagogical model of Sport Education within the framework of quality Physical Education and approached from the field of social and emotional learning, on a set of psychological variables: subjective well-being (quality of life related to health, positive affect and negative affect); trait emotional intelligence and social anxiety. A total number of 113 Compulsory Secondary Education students were involved, aged 12 to 15 years old, 44 of whom belonged to the control group (CG) and 69 to the experimental group (EG). A quasiexperimental design of repeated pretest and posttest measures with the CG was used. The results obtained in this investigation revealed that the intervention programme caused significant improvements in the subjective well-being and the trait emotional intelligence for the EG. These findings reinforce the pedagogical efficiency of the programme with regards to the aim that has been set. Likewise, the findings also highlight the suitability and appropriateness in terms of innovative teaching proposals. In the same way, the results showed relevant empirical contributions in this given school context due to its psychological benefits and the encouragement of healthy living.

The origin of neurodegenerative diseases is linked to the abnormal folding of disease-associated proteins. The traditional amyloid hypothesis has been a focal point of research, but recent findings suggest a more complex picture. This review explores the role of physiological conformation of aggregation-prone domain (also known as prion-like low complexity domain) and multiple co-misfolded proteins in neurodegenerative diseases. We highlight the importance of targeting multi-heterotypic misfolded proteins for effective treatments and emphasize the irreversible neurodegeneration stemming from the loss of physiological folding in prion-like disease-causing proteins underscores the criticality of refolding. Additionally, we introduce the concept of ReproFold Therapeutics, a novel approach aimed at restoring the cellular prion-like folding of disease-causing proteins to rebuild normal cross-β interactomes and mitigate neurodegeneration. Baicalein, a potential drug candidate for this approach, shows promise in vitro and in animal models. Moreover, prion-like low complexity domains implicated in neurodegeneration are also associated with other disorders such as diabetes, cancers, and mental illnesses. Understanding the core pathology of neurodegenerative diseases and the broader implications of prion-like LC domains could revolutionize healthcare approaches and policies worldwide.

Despite the availability of effective vaccines against COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide, pressing the need for new vaccines with improved breadth and durability. We developed an adjuvanted subunit vaccine against SARS-CoV-2 using recombinant receptor-binding domain (RBD) of spike with synthetic adjuvants targeting TLR7/8 (INI-4001) and TLR4 (INI-2002), co-delivered with aluminum hydroxide (AH) or aluminum phosphate (AP). The formulations were characterized for the quantities of RBD, INI-4001, and INI-2002 adsorbed onto the respective aluminum salts. Results indicated that at pH 6, the uncharged RBD (5.73 ± 4.2 mV) did not efficiently adsorb to the positively charged AH (22.68 ± 7.01 mV), whereas it adsorbed efficiently to the negatively-charged AP (-31.87 ± 0.33 mV). Alternatively, pre-adsorption of the TLR ligands to AH converted it to a negatively-charged particle, allowing for the efficient adsorption of RBD. RBD could also be directly adsorbed to AH at a pH of 8.1, which changed the charge of the RBD to negative. INI-4001 and INI-2002 efficiently to AH. Following vaccination in C57BL/6 mice, both aluminum salts promoted Th2-mediated immunity when used as the sole adjuvant. Co-delivery with TLR4 and/or TLR7/8 ligands efficiently promoted a switch to Th1-mediated immunity instead. Measurements of viral neutralization by serum antibodies demonstrated that the addition of TLR ligands to alum also greatly improved the neutralizing antibody response. These results indicate that the addition of a TLR7/8 and/or TLR4 agonist to a subunit vaccine containing RBD antigen and alum is a promising strategy for driving a Th1 response and neutralizing antibody titers targeting SARS-CoV-2.

Keywords: Wall-like RC columns; Strengthening; FRP; NSM rebars; Steel plates; Testing; FE modeling; Preloading.