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For the optimal survival of a species, an organism coordinates its reproductive decisions with the nutrient availability of its niche. Thus, nutrient-sensing pathways like insulin-IGF-1 signaling (IIS) play an important role in modulating cell division, oogenesis, and reproductive aging. Lowering of the IIS leads to the activation of the downstream FOXO transcription factor (TF) DAF-16 in Caenorhabditis elegans which promotes oocyte quality and delays reproductive aging. However, less is known about how the IIS axis responds to changes in cell cycle proteins, particularly in the somatic tissues. Here, we show a new aspect of the regulation of the germline by this nutrient-sensing axis. First, we show that the canonical G1-S cyclin, Cyclin D/CYD-1, regulates reproductive fidelity from the uterine tissue of wild-type worms. Then, we show that knocking down cyd-1 in the uterine tissue of an IIS receptor mutant arrests oogenesis at the pachytene stage of meiosis-1 in a DAF-16-dependent manner. We observe activated DAF-16-dependent deterioration of the somatic gonadal tissues like the sheath cells, and transcriptional de-regulation of the sperm-to-oocyte switch genes which may be the underlying reason for the absence of oogenesis. Deleting DAF-16 releases the arrest and leads to restoration of the somatic gonad but poor-quality oocytes are produced. Together, our study reveals the unrecognized cell non-autonomous interaction of Cyclin D/CYD-1 and FOXO/DAF-16 in the regulation of oogenesis and reproductive fidelity. Author summary: The conserved insulin-IGF-1 signaling (IIS) pathway in Caenorhabditis elegans is a neuroendocrine cascade that surveils the availability of nutrients as well as exposure to environmental and cellular stressors to regulate somatic development, reproduction and aging, both cell autonomously and non-autonomously. Lowering IIS flux activates the downstream FOXO transcription factor DAF-16 that mediates most of these responses. How this pathway responds to perturbations in cell cycle proteins to influence reproductive decision is less known. Here we show that the G1-S phase cyclin, Cyclin D/CYD-1 and the IIS nutrient-sensing axis crosstalk to regulate oogenesis and germ cell quality. In the wild-type worms, we found that CYD-1 in the uterine tissue regulates oocyte health and reproductive fidelity. Knocking down cyd-1, only in the somatic uterine tissue of IIS mutants, leads to a DAF-16-dependent arrest of oogenesis. Interestingly, we observed DAF-16-dependent destruction of the somatic gonadal tissues and de-regulation of the sperm-to-oocyte switch genes when CYD-1 is depleted in the uterus of animals with lower IIS. We speculate that defects in cell cycle proteins in the uterus may be interpreted by activated DAF-16 as a potential threat to progeny health that is unlikely to be rectified. So, our study unveils a new function of activated FOXO/DAF-16 and Cyclin D/CYD-1 in maintaining oocyte health and reproductive fidelity. [ABSTRACT FROM AUTHOR]

X-ray observations of active galactic nuclei (AGNs) reveal relativistic reflections from the innermost regions of accretion disks, which contain general-relativistic footprints caused by spinning supermassive black holes (SMBH). We anticipate the spin of a SMBH to be stable over the human timeframe, so brightness changes in the high-energy corona above the SMBH should slightly alter relativistic reflection. In this brief review, we discuss the latest developments in modeling relativistic reflection, as well as the rapid small variation in relativistic emission disclosed by the principal component analysis (PCA) of X-ray variability in AGN. PCA studies of X-ray spectra from AGNs have shown that relativistically blurred reflection has negligible fluctuations over the course of observations, which could originate from rapid (intrahour) intrinsic variations in near-horizon accretion flows and photon rings. The PCA technique is an effective way to disclose relativistic reflection from X-ray observations of AGNs, simplifying the complexity of largely variable X-ray data for automated spectral analysis with machine learning algorithms. [ABSTRACT FROM AUTHOR]

This paper presents a case study of participatory "demolition planning" for blighted, vacant properties in the legacy city of Flint, Michigan. It outlines how the Genesee County Land Bank Authority (GCLBA) used residents' responses to a survey about demolition priorities to create an algorithm that assigns demolition scores to blighted properties in Flint. The survey results showed that residents' top priority was demolishing blighted properties located directly next door to occupied properties. Fire-damaged properties, blighted properties in proximity to schools, and blighted properties located in highly occupied neighborhoods were the next highest priorities. There were few spatial differences in survey responses at the neighborhood (i.e., city ward) level. We discuss the implications of these findings and how other communities can adapt and improve upon the GCLBA's surveying and algorithm creation efforts. [ABSTRACT FROM AUTHOR]

Following an application from Alzchem Trostberg GmbH, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Austria, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to creatine and improvement in cognitive function. The Panel considers that the food constituent, creatine, is sufficiently characterised. An improvement in cognitive function in one or more of its domains is a beneficial physiological effect. The applicant identified 21 human intervention studies on creatine supplementation and measures of cognitive function through a literature search. Two additional studies published after the search was conducted were identified through the reference list of a meta‐analysis. In weighing the evidence, the Panel took into account that the acute effect of creatine on working memory, observed in two studies at 20 g/day for 5–7 days, was not seen at lower doses (2.2–14 g/day), or with continuous consumption (5 g/day for 6 weeks following a 5‐day loading phase). Furthermore, the effect on response inhibition at 20 g/day for 7 days was an isolated finding among 10 intervention studies in healthy individuals, with no effects observed on other cognitive domains. The Panel also considered that the three intervention studies conducted in diseased individuals do not support an effect of creatine supplementation on cognition, and that the available evidence for a mechanism by which creatine could exert the claimed effect is weak. The Panel concludes that a cause‐and‐effect relationship has not been established between creatine supplementation and an improvement in cognitive function in one or more of its domains. [ABSTRACT FROM AUTHOR]

A ring-opening protocol of epichlorohydrin with 2-ethylhexanol was investigated for the synthesis of the corresponding chlorohydrin ether. BuSnCl3 proved to be an efficient mild Lewis acid catalyst, yielding the product with high selectivity. A scalable flow synthesis was achieved by modifying the flow setup. The flow synthesis of the corresponding glycidyl ether from the chlorohydrin ether was also carried out in an efficient manner by using the basic treatment. [ABSTRACT FROM AUTHOR]

Background: There is renewed interest in the use of ancient herbal remedies for their potential health benefits, particularly in the psychological domain. One herb that is receiving growing attention is lemon balm (Melissa officinalis L.) which has received considerable interest for its influence on the brain. Lemon balm boasts an array of phytochemicals, including rosmarinic acid, citral, oleanolic acid, and ursolic acid, which are believed to underpin these effects on psychological well-being. Pharmacological evidence from animal and cellular work reveals that lemon balm and its components may modulate several brain signalling pathways, including GABAergic, cholinergic, and serotonergic systems. Results/Conclusions: Although further robust randomised controlled trials using lemon balm are required, existing research indicates that lemon balm holds promise as a calming agent exhibiting both anxiolytic and anti-depressant properties and can elicit cognitive and sleep-quality enhancement. [ABSTRACT FROM AUTHOR]

The problems concerning the insufficient level of associated petroleum gas (APG) processing are discussed. Various models are proposed for the chemical utilization of APG, including the production of synthesis gas, methanol, dimethyl ether, ammonia, as well as the processes of aromatization of hydrocarbons, etc. The possibility of using APG as a fuel for generating electricity is discussed. Attention is paid to the processes of APG purification from sulfur impurities. Difficulties and solutions to the problems of the energy sector of APG utilization are discussed. [ABSTRACT FROM AUTHOR]

Caenorhabditis elegans (C. elegans) has emerged as an outstanding model organism for investigating the aging process due to its shortened lifespan, well-defined genome, and accessibility of potent genetic tools. This review presents the current findings on chronological aging and photoaging in C. elegans, exploring the elaborate molecular pathways that control these processes. The progression of chronological aging is characterized by a gradual deterioration of physiological functions and is influenced by an interaction of genetic and environmental factors, including the insulin/insulin-like signaling (IIS) pathway. In contrast, photoaging is characterized by increased oxidative stress, DNA damage, and activation of stress response pathways induced by UV exposure. Although the genetic mechanisms of chronological aging in C. elegans have been characterized by extensive research, the pathways regulating photoaging are comparatively less well-studied. Here, we provide an overview of the current understanding of aging research, including the crucial genes and genetic pathways involved in the aging and photoaging processes of C. elegans. Understanding the complex interactions between these factors will provide invaluable insights into the molecular mechanisms underlying chronological aging and photoaging and may lead to novel therapeutic approaches and further studies for promoting healthy aging in humans. [ABSTRACT FROM AUTHOR]

Chemical compounds used to prevent and control fish disease often cause environmental hazards; thus, alternative approaches as new and effective strategies are needed. The current investigation was performed with the aim of exploring the effects of dietary Moldavian balm (MB, Dracocephalum moldavica L.) on the growth, immune parameters, and antioxidant status of common carp (Cyprinus carpio). Fish (n=300, w=3.80±0.02 g) in four groups in triplicates were supplemented with 0%, 0.5%, 1%, and 2% MB. After 42 days, it was found that feed supplements increased final weight (FW), weight gain (WG), and specific growth rate (SGR) and decreased the food conversion ratio (FCR) (P<0.05). In addition, fish supplemented with 2% MB significantly showed higher serum total protein (TP), alternative complement pathway (ACH50), and glutathione peroxidase (GPx) (P<0.05). The 0.5% MB-supplemented fish represented higher levels of LYZ, alkaline phosphatase (ALP), total Ig, and ACH50 in their skin mucus in comparison with the unsupplemented fish (P<0.05). The results also indicated that 2% MB resulted in a significantly higher expression level of intestinal tumor necrosis factor (TNF- α) (P<0.05); however, the level of LYZ, interleukin-1β (IL-1β), and TLRs decreased in supplemented fish. CAT and SOD expressions were increased in 0.5% MB supplement. In conclusion, MB could be recommended as an efficient feed additive to boost common carp's growth, immunity, and health status. [ABSTRACT FROM AUTHOR]

The elemental composition of the lunar surface provides insights into mechanisms of the formation and evolution of the Moon1,2. The chemical composition of lunar regolith have so far been precisely measured using the samples collected by the Apollo, Luna and Chang’e 5 missions, which are from equatorial to mid-latitude regions3,4; lunar meteorites, whose location of origin on the Moon is unknown5,6; and the in situ measurement from the Chang’e 3 and Chang’e 4 missions7–9, which are from the mid-latitude regions of the Moon. Here we report the first in situ measurements of the elemental abundances in the lunar southern high-latitude regions by the Alpha Particle X-ray Spectrometer (APXS) experiment10 aboard the Pragyan rover of India’s Chandrayaan-3 mission. The 23 measurements in the vicinity of the Chandrayaan-3 landing site show that the local lunar terrain in this region is fairly uniform and primarily composed of ferroan anorthosite (FAN), a product of the lunar magma ocean (LMO) crystallization. However, observation of relatively higher magnesium abundance with respect to calcium in APXS measurements suggests the mixing of further mafic material. The compositional uniformity over a few tens of metres around the Chandrayaan-3 landing site provides an excellent ground truth for remote-sensing observations.In situ measurements of the elemental abundances in the lunar southern high-latitude regions show that the local terrain is fairly uniform and mostly composed of ferroan anorthosite, a product of lunar magma ocean crystallization. [ABSTRACT FROM AUTHOR]

Equid alphaherpesvirus 1 (EHV-1) has been linked to the emergence of neurological disorders, with the horse racing industry experiencing significant impacts from outbreaks of equine herpesvirus myeloencephalopathy (EHM). Building robust immune memory before pathogen exposure enables rapid recognition and elimination, preventing infection. This is crucial for effectively managing EHV-1. Removing neuropathogenic factors and immune evasion genes to develop live attenuated vaccines appears to be a successful strategy for EHV-1 vaccines. We created mutant viruses without ORF38 and ORF37/38 and validated their neuropathogenicity and immunogenicity in hamsters. The ∆ORF38 strain caused brain tissue damage at high doses, whereas the ∆ORF37/38 strain did not. Dexamethasone was used to confirm latent herpesvirus infection and reactivation. Dexamethasone injection increased viral DNA load in the brains of hamsters infected with the parental and ∆ORF38 strains, but not in those infected with the ∆ORF37/38 strain. Immunizing hamsters intranasally with the ∆ORF37/38 strain as a live vaccine produced a stronger immune response compared to the ∆ORF38 strain at the same dose. The hamsters demonstrated effective protection against a lethal challenge with the parental strain. This suggests that the deletion of ORF37/38 may effectively inhibit latent viral infection, reduce the neuropathogenicity of EHV-1, and induce a protective immune response. [ABSTRACT FROM AUTHOR]

Seaweeds are regarded as one of the greatest sources of biologically active substances with potent biological activities among the innumerable marine organisms. It finds numerous industrial applications in areas such as food and dairy, pharmaceuticals, medicine, cosmeceuticals, and nutraceuticals because it is a significant source of bioactive ingredients. It has been reported that the brown seaweed Padina boergesenii, also known as the leafy rolled-blade alga, has anti-venom activity against the Naja nigricollis. However, it is still unclear how these actions are prompted by it. Using in vitro and in vivo animal models, the current work seeks to evaluate the mechanistic anti-venom activity of Padina boergesenii methanolic extract (PBME) against Naja naja (N. naja) venom. The total antioxidant activity, deoxyribose radical scavenging activity, DPPH (2, 2-diphenyl-1-picrylhydrazylhydrate), and ferric reducing antioxidant power (FRAP) assay were used to measure the in vitro antioxidant activity. In vivo (venom neutralization, suppression of hemorrhagic, necrotic, myotoxic, and paw edema) and in vitro (inhibiting phospholipase A2 and procoagulant effects) anti-venom properties of PBME were studied against N. naja venoms. In every anti-oxidant test, the extracts demonstrated potency. Naja naja venom's median lethal dose was 0.5943 mg/kg of body weight. The N. naja venom–induced phospholipase A2, hemorrhagic, necrotic, myotoxic, and paw edema in mice were all considerably reduced by PBME. Animals exposed to PBME substantially and dose-dependently neutralized the N. naja venom by various mechanisms. Therefore, additional research into PBME's anti-venom characteristics as a neutralizing agent for snake venoms is a possibility. [ABSTRACT FROM AUTHOR]

This qualitative study explored the role of neglected properties and neighborhood environment characteristics on a sample of New Orleans, Louisiana residents' health and well-being, sense of community, sense of safety, and civic engagement. We hypothesized that residents would identify conditions of their neighborhood's physical environment, including neglected properties, as one factor that impacted their health and other aspects of well-being. Seventy-four (N = 74) participants, including women, men, youth, young adults, and community leaders, took part in 11 focus groups (n = 51) and 23 key informant interviews. Thematic content analysis through inductive and deductive coding cycles of interview transcripts revealed five main categories related to urban neighborhood-built and social environments: 1) health and well-being, 2) sense of community, 3) sense of safety, 4) civic engagement, and 5) youth and family violence. Ten themes were developed and included, for example, the role of neighborhoods in delineating access to health-promoting characteristics and resources; the role of neighborhood social networks as crime prevention strategies; resident-led decision-making in neighborhood improvements; the negative impact of neglected properties; and the role of the local government in improving physical infrastructure. These findings affirm that residents were aware of and impacted by the cyclical nature of built environment neglect on health and well-being, community violence, neighborhood cohesion, civic engagement, and youth violence. Participants recommended improving neighborhood conditions to shift resident mindsets about the health of neighborhoods, reduce violence, and improve quality of life. [ABSTRACT FROM AUTHOR]

Cochlear implants (CI) allow deaf patients to improve language perception and improving their emotional valence assessment. Electroencephalographic (EEG) measures were employed so far to improve CI programming reliability and to evaluate listening effort in auditory tasks, which are particularly useful in conditions when subjective evaluations are scarcely appliable or reliable. Unfortunately, the presence of CI on the scalp introduces an electrical artifact coupled to EEG signals that masks physiological features recorded by electrodes close to the site of implant. Currently, methods for CI artifact removal have been developed for very specific EEG montages or protocols, while others require many scalp electrodes. In this study, we propose a method based on the Multi-channel Wiener filter (MWF) to overcome those shortcomings. Nine children with unilateral CI and nine age-matched normal hearing children (control) participated in the study. EEG data were acquired on a relatively low number of electrodes (n = 16) during resting condition and during an auditory task. The obtained results obtained allowed to characterize CI artifact on the affected electrode and to significantly reduce, if not remove it through MWF filtering. Moreover, the results indicate, by comparing the two sample populations, that the EEG data loss is minimal in CI users after filtering, and that data maintain EEG physiological characteristics. [ABSTRACT FROM AUTHOR]

Equid alphaherpesvirus 1 (EqAHV1) is a viral pathogen known to cause respiratory disease, neurologic syndromes, and abortion storms in horses. Currently, there are no vaccines that provide complete protection against EqAHV1. Marker vaccines and the differentiation of infected and vaccinated animals (DIVA) strategy are effective for preventing and controlling outbreaks but have not been used for the prevention of EqAHV1 infection. Glycoprotein 2 (gp2), located on the envelope of viruses (EqAHV1), exhibits high antigenicity and functions as amolecular marker for DIVA. In this study, a series of EqAHV1 mutants with deletion of gp2 along with other virulence genes (TK, UL24/TK, gI/gE) were engineered. The mutant viruses were studied in vitro and then in an in vivo experiment using Golden Syrian hamsters to assess the extent of viral attenuation and the immune response elicited by the mutant viruses in comparison to the wild-type (WT) virus. Compared with the WT strain, the YM2019 Δgp2, ΔTK/gp2, and αUL24/TK/gp2 strains exhibited reduced growth in RK-13 cells, while the DgI/gE/gp2 strain exhibited significantly impaired proliferation. The YM2019 Δgp2 strain induced clinical signs and mortality in hamsters. In contrast, the YM2019 ΔTK/gp2 and αUL24/TK/gp2 variants displayed diminished pathogenicity, causing no observable clinical signs or fatalities. Immunization with nasal vaccines containing YM2019 ΔTK/gp2 and αUL24/TK/gp2 elicited a robust immune response in hamsters. In particular, compared with the vaccine containing the ΔTK/gp2 strain, the vaccine containing the αUL24/TK/gp2 strain demonstrated enhanced immune protection upon challenge with the WT virus. Furthermore, an ELISA for gp2 was established and refined to accurately differentiate between infected and vaccinated animals. These results confirm that the αUL24/TK/gp2 strain is a safe and effective live attenuated vaccine candidate for controlling EqAHV1 infection. [ABSTRACT FROM AUTHOR]

Studies on numerous species have demonstrated strikingly conserved mechanisms that determine the aging process, from yeasts to worms, flies, zebrafish, mice, and humans. The fruit fly Drosophila melanogaster is an excellent model organism for studying the biological basis of normal aging and etiology of age-related diseases. Since its inception in 1967, the Bloomington Drosophila Stock Center (BDSC) has grown into the largest collection of documented D. melanogaster strains (currently > 91,000). This paper aims to briefly review conserved mechanisms of aging and provides a guide to help users understand the organization of stock listings on the BDSC website and familiarize themselves with the search functions on BDSC and FlyBase, with an emphasis on using genes in conserved pathways as examples to find stocks for aging studies. [ABSTRACT FROM AUTHOR]

Imiqualines are analogues of the immunomodulatory drug imiquimod. EAPB02303, the lead of the second-generation imiqualines, is characterized by significant anti-tumor effects with IC50s in the nanomolar range. We used Caenorhabditis elegans transgenic and mutant strains of two key signaling pathways (PI3K-Akt and Ras-MAPK) disrupted in human cancers to investigate the mode of action of EAPB02303. The ability of this imiqualine to inhibit the insulin/IGF1 signaling (IIS) pathway via the PI3K-Akt kinase cascade was explored through assessing the lifespan of wild-type worms. Micromolar doses of EAPB02303 significantly enhanced longevity of N2 strain and led to the nuclear translocation and subsequent activation of transcription factor DAF-16, the only forkhead box transcription factor class O (Fox O) homolog in C. elegans. Moreover, EAPB02303 significantly reduced the multivulva phenotype in let-60/Ras mutant strains MT2124 and MT4698, indicative of its mode of action through the Ras pathway. In summary, we showed that EAPB02303 potently reduced the activity of IIS and Ras-MAPK signaling in C. elegans. Our results revealed the mechanism of action of EAPB02303 against human cancers associated with hyperactivated IIS pathway and oncogenic Ras mutations. [ABSTRACT FROM AUTHOR]

Classical genetic analysis is invaluable for understanding the genetic interactions underlying specific phenotypes, but requires laborious and subjective experiments to characterize polygenic and quantitative traits. Contrarily, transcriptomic analysis enables the simultaneous and objective identification of multiple genes whose expression changes are associated with specific phenotypes. Here, we conducted transcriptomic analysis of genes crucial for longevity using datasets with daf‐2/insulin/IGF‐1 receptor mutant Caenorhabditis elegans. Our analysis unraveled multiple epistatic relationships at the transcriptomic level, in addition to verifying genetically established interactions. Our combinatorial analysis also revealed transcriptomic changes associated with longevity conferred by daf‐2 mutations. In particular, we demonstrated that the extent of lifespan changes caused by various mutant alleles of the longevity transcription factor daf‐16/FOXO matched their effects on transcriptomic changes in daf‐2 mutants. We identified specific aging‐regulating signaling pathways and subsets of structural and functional RNA elements altered by different genes in daf‐2 mutants. Lastly, we elucidated the functional cooperation between several longevity regulators, based on the combination of transcriptomic and molecular genetic analysis. These data suggest that different biological processes coordinately exert their effects on longevity in biological networks. Together our work demonstrates the utility of transcriptomic dissection analysis for identifying important genetic interactions for physiological processes, including aging and longevity. [ABSTRACT FROM AUTHOR]

Background: Most Japanese medical schools likely continue to rely on peer physical examination (PPE) as a tool to for teaching physical examination skills to students. However, the attitudes of medical students in Japan toward PPEs have not be identified. Therefore, we evaluated students' attitudes toward PPE in a Japanese medical school as a preparation for developing a PPE policy tailored to the context of Japanese culture. Methods: We conducted a mixed-methods study with an explanatory sequential approach, in which qualitative data were used to interpret the quantitative findings. Surveys and interviews were conducted with medical students and junior residents at a Japanese university. A total of 63 medical students and 50 junior residents responded to the questionnaire. We interviewed 16 participants to reach theoretical saturation and investigated the attitudes of medical students toward PPE and the themes emerging from the interview data, providing detailed descriptions of the quantitative findings. Results: Female participants were significantly more likely than male participants to report varying degrees of resistance to being a model patient during PPE (male: 59.7%, female: 87%, p < 0.001). Most of the participants who took on the role of patients that involved undressing were males. The participants expected improvements in issues related to the guarantee of freedom to refuse to be a model patient and measures to protect confidentiality. Approximately 22% of the participants reported that they witnessed incidental findings (including variations within the normal range) in front of other students during PPE. Conclusions: The findings imply that medical students expect high levels of autonomy and confidentiality when volunteering as model patients during PPE. Thus, developing a PPE policy suitable for Japanese culture may be effective in establishing a student-centered PPE environment. [ABSTRACT FROM AUTHOR]

Patients with multiple sclerosis (MS) have a lower quality of life (QoL) than the general population. Rehabilitation is an essential part of the comprehensive treatment of MS patients. The aim was to determine the influence of complex physical therapy on the QoL of MS patients and the association of functional status with certain domains of health-related QoL. We followed 58 MS patients. The complex kinesitherapy used the Bobath concept and occupational therapy with the use of robot-assisted rehabilitation for the upper extremities. Before the start of rehabilitation and at the end, functional status was assessed by the Expanded Disability Status Scale (EDSS) and Berg Balance Scale (BBS). QoL was assessed through the standardized SF36 test and summarized into two scores: physical health component score and mental health component score. The average age of patients was 49.38 years. There was a significant improvement in all patients after the therapy, both in functional status and in QoL. There were no significant correlations between the EDSS and BBS with QoL parameters (individual SF36 categories and two summary scores). Duration of the disease correlated with the EDSS and BBS, but not with QoL. The age of patients did not correlate with functional status or with QoL. Physical therapy improves both functional status and QoL, but improvements do not correlate. There is a need to incorporate QoL assessment into assessments of disease severity, progression, and treatment success to obtain the most relevant results in creating the right treatment strategy. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T-cell therapy has exhibited remarkable efficacy in the treatment of haematological malignancies, yet its application in solid tumours is hindered by the immunosuppressive tumour microenvironment (TME). In this study, a novel SS1-TREM1/DAP12-BB CAR-T cell was devised to target ovarian cancer and further engineered to co-express the dominant-negative TGF-β receptor 2 (DNR) to combat CAR-T cell exhaustion in TME. The incorporation of DNR effectively blocked TGF-β signalling, thereby enhancing CAR-T cell survival and antitumor activity in a TGF-β1-rich environment. In vivo evaluations demonstrated that DNR co-expression potentiated the antitumor efficacy of TREM1/DAP12-BB CAR-T cells and conferred resilience against tumour rechallenge. These findings underscore the broad potential of DNR co-expression in CAR design, presenting a novel therapeutic strategy for patients with recurrent ovarian cancer., (© 2025 John Wiley & Sons Ltd.)

In Caenorhabditis elegans (C. elegans), there is a single FOXO transcription factor homolog, encoded by the gene, daf-16. As a central regulator for multiple pathways, DAF-16 integrates these signals to result in changes in longevity, development, fat storage, stress resistance, innate immunity, and reproduction. One of the main advantages of using C. elegans is the ability to study FOXO in the context of the whole animal. Therefore, manipulating the levels or the activity of daf-16 results in visible, scorable phenotypic changes. DAF-16 is the downstream target of the conserved insulin/IGF-1 signaling (IIS) pathway, a PI 3-kinase signaling cascade that ultimately controls its nuclear localization. Since the IIS pathway is a major regulator of lifespan, almost all studies of lifespan modulation examine the requirement of daf-16. More recently, lifespan analysis has been accompanied by healthspan analysis, referring to the time an animal is healthy. In this chapter, I will focus on the assays to assess lifespan and healthspan of C. elegans FOXO/daf-16, in the context of a whole animal., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

FOXO transcription factors belong to the forkhead protein family and are distinguished by their unique forkhead (FKH) DNA-binding domain. In the realm of mammals, four FOXO paralogs are recognized: FOXO1, FOXO3, FOXO4, and FOXO6. These paralogs are evolutionary counterparts of the daf-16 gene discovered in the nematode C. elegans. A key feature shared by these paralogs is a consensus binding site known as the DAF-16 family protein-binding site (DBE: 5'-TTGTTTAC-3'). The functional outcome of FOXO transcription factors primarily hinges on their affinity for these specific binding sites within the promoters of their target genes. Nevertheless, it is worth noting that many of these target genes exhibit tissue-specific expression patterns. Consequently, there is not a single FOXO target gene whose expression can reliably serve as a universal indicator of FOXO activity across all cell types and tissues or in response to all stimuli. In light of these considerations, we present a collection of target genes that, when collectively assessed, can accurately gauge FOXO activation. In this chapter, we outline a specific protocol for utilizing quantitative reverse transcription polymerase chain reaction (qRT-PCR) to measure the expression levels of these genes., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: In volleyball, jump execution is critical for the match outcome. Game-play-related neuromuscular impairments may manifest as decreased jump height (JH) or increased jump total duration, both of which are pivotal for performance. To investigate changes in JH and kinetics with game play, the authors conducted a prospective exploratory analysis using minimal-effect testing (MET) and equivalence testing with the 2 one-sided tests procedure, univariate, and bivariate functional principal component analysis, respectively. Methods: Twelve male varsity athletes completed 3-set matches on 2 consecutive days. Countermovement jumps were performed on a force platform immediately prematch and postmatch on days 1 and 2 and once on days 3 and 4. Results: Across sessions, JH was equivalent (P <.022, equivalence test), while total duration reported inconclusive changes (P >.227). After match 2, MET indicated that relative force at zero velocity (P =.036) decreased, while braking duration (P =.040) and time to peak force (P =.048) increased compared with baseline. With the first and second functional principal components, these alterations, together with decreased relative braking rate of force development (P =.092), were already evident after match 1. On day 4, MET indicated that relative peak force (P =.049), relative force at zero velocity (P =.023), and relative braking rate of force development (P =.021) decreased, whereas braking duration (P =.025) increased from baseline. Conclusions: Impairments in jump kinetics were evident from variables related to the countermovement-jump braking phase, while JH was equivalent. In addition to these experimental findings, the present research provides information for the choice of sample size and smallest effect size of interest when using MET and 1- and 2-dimensional analyses for countermovement-jump height and kinetics. [ABSTRACT FROM AUTHOR]

Equine herpesvirus‐1 (EHV‐1) is a highly prevalent and frequently pathogenic infection of equids. The most serious clinical consequences of infection are abortion and equine herpesvirus myeloencephalopathy (EHM). The previous consensus statement was published in 2009 and considered pathogenesis, strain variation, epidemiology, diagnostic testing, vaccination, outbreak prevention and control, and treatment. A recent survey of American College of Veterinary Internal Medicine large animal diplomates identified the need for a revision to this original consensus statement. This updated consensus statement is underpinned by 4 systematic reviews that addressed key questions concerning vaccination, pharmaceutical treatment, pathogenesis, and diagnostic testing. Evidence for successful vaccination against, or effective treatment of EHV‐1 infection was limited, and improvements in experimental design and reporting of results are needed in future studies of this important disease. This consensus statement also updates the topics considered previously in 2009. [ABSTRACT FROM AUTHOR]

Background: Equine herpes virus type 1 (EHV‐1) infection in horses is associated with upper respiratory disease, neurological disease, abortions, and neonatal death. Review Question: Does pharmacological therapy decrease either the incidence or severity of disease or infection caused by EHV‐1 in domesticated horses? Methods: A systematic review was preformed searching AGRICOLA, CAB Abstracts, Cochrane, PubMed, Web of Science, and WHO Global Health Index Medicus Regional Databases to identify articles published before February 15, 2021. Selection criteria were original research reports published in peer reviewed journals, and studies investigating in vivo use of therapeutic agents for prevention or treatment of EHV‐1 in horses. Outcomes assessed included measures related to clinical outcomes that reflect symptomatic EHV‐1 infection or virus infection. We evaluated risk of bias and performed a GRADE evaluation of the quality of evidence for interventions. Results: A total of 7009 unique studies were identified, of which 9 met the inclusion criteria. Two studies evaluated valacyclovir or small interfering RNAs, and single studies evaluated the use of a Parapoxvirus ovis‐based immunomodulator, human alpha interferon, an herbal supplement, a cytosine analog, and heparin. The level of evidence ranged between randomized controlled studies and observational trials. The risk of bias was moderate to high and sample sizes were small. Most studies reported either no benefit or minimal efficacy of the intervention tested. Conclusions and Clinical Importance: Our review indicates minimal or limited benefit either as a prophylactic or post‐exposure treatment for any of the studied interventions in the mitigation of EHV‐1‐associated disease outcome. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired daily functioning. While there is currently no cure for AD, several pharmacotherapeutic targets and management strategies have been explored. Additionally, traditional medicinal plants have gained attention for their potential role in AD management. Pharmacotherapeutic targets in AD include amyloid-beta (Aβ) aggregation, tau protein hyperphosphorylation, neuroinflammation, oxidative stress, and cholinergic dysfunction. Traditional medicinal plants, such as Ginkgo biloba, Huperzia serrata, Curcuma longa (turmeric), and Panax ginseng, have demonstrated the ability to modulate these targets through their bioactive compounds. Ginkgo biloba, for instance, contains flavonoids and terpenoids that exhibit neuroprotective effects by reducing Aβ deposition and enhancing cerebral blood flow. Huperzia serrata, a natural source of huperzine A, has acetylcholinesterase-inhibiting properties, thus improving cholinergic function. Curcuma longa, enriched with curcumin, exhibits anti-inflammatory and antioxidant effects, potentially mitigating neuroinflammation and oxidative stress. Panax ginseng's ginsenosides have shown neuroprotective and anti-amyloidogenic properties. The investigation of traditional medicinal plants as a complementary approach to AD management offers several advantages, including a lower risk of adverse effects and potential multi-target interactions. Furthermore, the cultural knowledge and utilization of these plants provide a rich source of information for the development of new therapies. However, further research is necessary to elucidate the precise mechanisms of action, standardize preparations, and assess the safety and efficacy of these natural remedies. Integrating traditional medicinal-plant-based therapies with modern pharmacotherapies may hold the key to a more comprehensive and effective approach to AD treatment. This review aims to explore the pharmacotherapeutic targets in AD and assess the potential of traditional medicinal plants in its management. [ABSTRACT FROM AUTHOR]

Objective To assess whether neonatal morbidities evident by the time of hospital discharge are associated with subsequent cerebral palsy (CP) or death. Study Design This is a secondary analysis of data from a multicenter placebo-controlled trial of magnesium sulfate for the prevention of CP. The association between prespecified intermediate neonatal outcomes (n = 11) and demographic and clinical factors (n = 10) evident by the time of discharge among surviving infants (n = 1889) and the primary outcome of death or moderate/severe CP at age 2 (n = 73) was estimated, and a prediction model was created. Results Gestational age in weeks at delivery (odds ratio [OR]: 0.74, 95% confidence interval [CI]: 0.67–0.83), grade III or IV intraventricular hemorrhage (IVH) (OR: 5.3, CI: 2.1–13.1), periventricular leukomalacia (PVL) (OR: 46.4, CI: 20.6–104.6), and male gender (OR: 2.5, CI: 1.4–4.5) were associated with death or moderate/severe CP by age 2. Outcomes not significantly associated with the primary outcome included respiratory distress syndrome, bronchopulmonary dysplasia, seizure, necrotizing enterocolitis, neonatal hypotension, 5-minute Apgar score, sepsis, and retinopathy of prematurity. Using all patients, the receiver operating characteristic curve for the final prediction model had an area under the curve of 0.84 (CI: 0.78–0.89). Using these data, the risk of death or developing CP by age 2 can be calculated for individual surviving infants. Conclusion IVH and PVL were the only neonatal complications evident at discharge that contributed to an individual infant's risk of the long-term outcomes of death or CP by age 2. A model that includes these morbidities, gestational age at delivery, and gender is predictive of subsequent neurologic sequelae. Key Points Factors known at hospital discharge are identified which are independently associated with death or CP by age 2. A model was created and validated using these findings to counsel parents. The risk of death or CP can be calculated at the time of hospital discharge. [ABSTRACT FROM AUTHOR]

Purpose: This paper aims to explore how environmental employment can promote desistance among criminalised children. Research demonstrates that being immersed in and interacting with the natural environment has a positive impact upon well-being and behaviour, including reduced aggressive and violent behaviours. However, how exposure to the natural environment might promote desistance amongst children with persistent criminal involvement is unclear. Design/methodology/approach: This paper examines, through semi-structured interviews and participant observations, the experiences of n = 23 criminalised children aged 16–18 employed in outdoor work at a UK social enterprise. Findings: The findings demonstrate how working in the natural environment can provide a safe space for children, where they can build positive relationships, learn valuable skills and reconnect with the world outside of the high-pressure, conflict-driven spaces in which they typically occupy. Originality/value: This research highlights the relevance of the setting in which child rehabilitation takes place and the potential role of natural environments in providing places and opportunities which support pro-social identity development and desistance for children. [ABSTRACT FROM AUTHOR]

Finding new interventions that slow ageing and maintain human health is a huge challenge of our time. The nematode Caenorhabditis elegans offers a rapid in vivo method to determine whether a compound extends its 2 to 3-week lifespan. Measuring lifespan is the standard method to monitor ageing, but a compound that extends lifespan will not necessarily maintain health. Here, we describe the automated monitoring of C. elegans movement from early to mid-adulthood as a faster healthspan-based method to measure ageing. Using the WormGazer™ technology, multiple Petri dishes each containing several C. elegans worms are imaged simultaneously and non-invasively by an array of cameras that can be scaled easily. This approach demonstrates that most functional decline in C. elegans occurs during the first week of adulthood. We find 7 days of imaging is sufficient to measure the dose-dependent efficacy of sulfamethoxazole to slow ageing, compared to 40 days required for a parallel lifespan experiment. Understanding any negative consequences of interventions that slow ageing is important. We show that the long-lived mutant age-1(hx546) stays active for longer than the wild type but it moves slower in early adulthood. Thus, continuous analysis of movement can rapidly identify interventions that slow ageing while simultaneously revealing any negative effects on health. [ABSTRACT FROM AUTHOR]

Studies were conducted in the temperate forests of the European part of Russia (territory of the Republic of Mordovia). Beer traps with bait made of beer and sugar were used for the studies. Three plots were selected for the study, which differed in the composition of plants at the edges, adjacent open ecosystems and types of forest ecosystems. The forest was adjacent to this open ecosystem and there was no transition zone of shrubs. Eight traps were used in each plot (1,2 - edge-below, 3,4 - edge-above, 5,6 - forest interior-below, 7,8 - forest interiorabove). They were located 1.5 m (further named as "below" traps) and 7.5 m (further named as "above" traps) from the ground level. During the experiments, 52306 specimens from 28 families of Diptera were captured. In terms of total abundance, representatives of 25 families were present in the lower traps and species from 27 families were present in the upper traps. The general pattern was the highest abundance of Diptera at the edges in all plots. Nine families (Tipulidae, Anisopodidae, Lonchaeidae, Milichiidae, Drosophilidae, Anthomyiidae, Fanniidae, Muscidae, Calliphoridae) accounted for 93.3% of all Diptera abundance in all plots. The families Tipulidae, and Drosophilidae were the most abundant in lower traps within forest ecosystems. The families Lonchaeidae, Milichiidae, Anthomyiidae, Fanniidae, and Muscidae were most abundant in upper traps at the edges of forests. The families Anisopodidae, Calliphoridae were the most abundant in the lower down edges. [ABSTRACT FROM AUTHOR]

Background: Recent reports have highlighted the significance of plant bioactive components in drug development targeting neurodegenerative disorders such as Alzheimer's disease (AD). Thus, the current study assessed antioxidant activity and enzyme inhibitory activity of the aqueous extract of Talinum triangulare leave (AETt) as well as molecular docking/simulation of the identified phytonutrients against human cholinesterase activities. Methods: In vitro assays were carried out to assess the 2,2- azinobis (3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) cation radicals and cholinesterase inhibitory activities of AETt using standard protocols. High performance liquid chromatography coupled with diode-array detection (HPLC–DAD) was employed to identify compounds in AETt. Also, for computational analysis, identified bioactive compounds from AETt were docked using Schrodinger's GLIDE against human cholinesterase obtained from the protein data bank (https://www.rcsb.org/). Results: The results revealed that AETt exhibited a significant concentration-dependent inhibition against ABTS cation radicals (IC50 = 308.26 ± 4.36 µg/ml) with butylated hydroxytoluene (BHT) as the reference. Similarly, AETt demonstrated a significant inhibition against acetylcholinesterase (AChE, IC50 = 326.49 ± 2.01 µg/ml) and butyrylcholinesterase (BChE, IC50 = 219.86 ± 4.13 µg/ml) activities with galanthamine as the control. Molecular docking and simulation analyses revealed rutin and quercetin as potential hits from AETt, having showed strong binding energies for both the AChE and BChE. In addition, these findings were substantiated by analyses, including radius of gyration, root mean square fluctuation, root mean square deviation, as well as mode similarity and principal component analyses. Conclusion: Overall, this study offers valuable insights into the interactions and dynamics of protein–ligand complexes, offering a basis for further drug development targeting these proteins in AD. [ABSTRACT FROM AUTHOR]

This study examined the effect of creatine nitrate and caffeine alone and combined on exercise performance and cognitive function in resistance-trained athletes. In a double-blind, randomized crossover trial, twelve resistance-trained male athletes were supplemented with 7 days of creatine nitrate (5 g/day), caffeine (400 mg/day), and a combination of creatine nitrate and caffeine. The study involved twelve resistance-trained male athletes who initially provided a blood sample for comprehensive safety analysis, including tests for key enzymes and a lipid profile, and then performed standardized resistance exercises—bench and leg press at 70% 1RM—and a Wingate anaerobic power test. Cognitive function and cardiovascular responses were also examined forty-five minutes after supplementation. Creatine nitrate and caffeine that were co-ingested significantly enhanced cognitive function, as indicated by improved scores in the Stroop Word–Color Interference test (p = 0.04; effect size = 0.163). Co-ingestion was more effective than caffeine alone in enhancing cognitive performance. In contrast, no significant enhancements in exercise performance were observed. The co-ingestion of creatine nitrate and caffeine improved cognitive function, particularly in cognitive interference tasks, without altering short-term exercise performance. Furthermore, no adverse events were reported. Overall, the co-ingestion of creatine nitrate and caffeine appears to enhance cognition without any reported side effects for up to seven days. [ABSTRACT FROM AUTHOR]

Stem cells are pivotal players in the intricate dance of embryonic development, tissue maintenance, and regeneration. Their behavior is delicately balanced between maintaining their pluripotency and differentiating as needed. Disruptions in this balance can lead to a spectrum of diseases, underscoring the importance of unraveling the complex molecular mechanisms that govern stem cell fate. Forkhead box O (FOXO) proteins, a family of transcription factors, are at the heart of this intricate regulation, influencing a myriad of cellular processes such as survival, metabolism, and DNA repair. Their multifaceted role in steering the destiny of stem cells is evident, as they wield influence over self-renewal, quiescence, and lineage-specific differentiation in both embryonic and adult stem cells. This review delves into the structural and regulatory intricacies of FOXO transcription factors, shedding light on their pivotal roles in shaping the fate of stem cells. By providing insights into the specific functions of FOXO in determining stem cell fate, this review aims to pave the way for targeted interventions that could modulate stem cell behavior and potentially revolutionize the treatment and prevention of diseases. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 infection in children is usually asymptomatic/mild. However, some patients may develop critical forms. We aimed to describe characteristics and evaluate the factors associated to in-hospital mortality of patients with critical COVID-19/MIS-C in the Amazonian region. This multicenter prospective cohort included critically ill children (1 mo–18 years old), with confirmed COVID-19/MIS-C admitted to 3 tertiary Pediatric Intensive Care Units (PICU) in the Brazilian Amazon, between April/2020 and May/2023. The main outcome was in-hospital mortality and were evaluated using a multivariable Cox proportional regression. We adjusted the model for pediatric risk of mortality score version IV (PRISMIV) score and age/comorbidity. 266 patients were assessed with 187 in the severe COVID-19 group, 79 included in the MIS-C group. In the severe COVID-19 group 108 (57.8%) were male, median age was 23 months, 95 (50.8%) were up to 2 years of age. Forty-two (22.5%) patients in this group died during follow-up in a median time of 11 days (IQR, 2–28). In the MIS-C group, 56 (70.9%) were male, median age was 23 months and median follow-up was 162 days (range, 3–202). Death occurred in 17 (21.5%) patients with a median death time of 7 (IQR, 4–13) days. The mortality was associated with higher levels of Vasoactive Inotropic-Score (VIS), presence of acute respiratory distress syndrome (ARDS), higher levels of Erythrocyte Sedimentation Rate, (ESR) and thrombocytopenia. Critically ill patients with severe COVID-19 and MIS-C from the Brazilian Amazon showed a high mortality rate, within 12 days of hospitalization. [ABSTRACT FROM AUTHOR]

An animal's ability to sense odors declines during aging, and its olfactory drive is tuned by internal states such as satiety. However, whether internal states modulate an age-dependent decline in odor sensation is unknown. To address this issue, we utilized the nematode Caenorhabditis elegans and compared their chemotaxis abilities toward attractive odorants when aged under different dietary conditions. Feeding with the standard laboratory diet, Escherichia coli attenuated the chemotaxis ability toward diacetyl, isoamyl alcohol, and benzaldehyde when aged. On the other hand, feeding with either the lactic acid bacteria Lactobacillus reuteri or food deprivation selectively maintained the chemotaxis ability toward diacetyl. Our results suggest that ingestion of E. coli causes age-dependent chemotaxis decline. The changes in the chemotaxis behavior are attributed to the different expressions of diacetyl receptor odr-10, and the chemotaxis behavior of aged animals under food deprivation is shown to be dependent on daf-16. Our study demonstrates the molecular mechanism of how diet shapes the trajectory of age-dependent decline in chemosensory behaviors. [ABSTRACT FROM AUTHOR]

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