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The anaerobic acid production experiments were conducted with the pretreated kitchen waste under pH adjustment. The results showed that pH 8 was considered to be the most suitable condition for acid production, especially for the formation of acetic acid and propionic acid. The average value of total volatile fatty acid at pH 8 was 8814 mg COD/L, 1.5 times of that under blank condition. The average yield of acetic acid and propionic acid was 3302 mg COD/L and 2891 mg COD/L, respectively. The activities of key functional enzymes such as phosphotransacetylase, acetokinase, oxaloacetate transcarboxylase and succinyl-coA transferase were all enhanced. To further explore the regulatory mechanisms within the system, the distribution of microorganisms at different levels in the fermentation system was obtained by microbial sequencing, results indicating that the relative abundances of Clostridiales, Bacteroidales, Chloroflexi, Clostridium, Bacteroidetes and Propionibacteriales, which were great contributors for the hydrolysis and acidification, increased rapidly at pH 8 compared with the blank group. Besides, the proportion of genes encoding key enzymes was generally increased, which further verified the mechanism of hydrolytic acidification and acetic acid production of organic matter under pH regulation.
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Ácidos Graxos Voláteis , Concentração de Íons de Hidrogênio , Ácidos Graxos Voláteis/metabolismo , Fermentação , Ácido Acético/metabolismo , Reatores BiológicosRESUMO
Recent years have seen increasing recognition of the scientific, economic and ethical benefits of the use of non-animal models in advancing preclinical research, giving reason to rethink the application and framework of the Three Rs. However, to benefit from the economic advantages of shifting to such alternative methods, and to realise Australia's drug development potential, legislative reform is essential. Such reform should be responsive to international regulations that encourage the use of animal-free methods, and be coupled with a corresponding re-evaluation of current Three Rs frameworks and principles. If these supportive changes, and the recommendations from the 2023 Australian Commonwealth Scientific and Industrial Research Organisation (CSIRO) Futures Non-animal models report, are implemented concurrently - with government support paramount- then a new gold standard for scientific research in Australia could be created in which the use of non-animal models and animal-free methods is the default.
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Alternativas aos Testes com Animais , Austrália , Alternativas aos Testes com Animais/legislação & jurisprudência , Animais , Humanos , Experimentação Animal/legislação & jurisprudência , Experimentação Animal/éticaRESUMO
Cellular redox homeostasis is essential for maintaining cellular activities, such as DNA synthesis and gene expression. Inspired by this, new therapeutic interventions have been rapidly developed to modulate the intracellular redox state using artificial transmembrane electron transport. However, current approaches that rely on external electric field polarization can disrupt cellular functions, limiting their in vivo application. Therefore, it is crucial to develop novel electric-field-free modulation methods. In this work, we for the first time found that graphene could spontaneously insert into living cell membranes and serve as an electron tunnel to regulate intracellular reactive oxygen species and NADH based on the spontaneous bipolar electrochemical reaction mechanism. This work provides a wireless and electric-field-free approach to regulating cellular redox states directly and offers possibilities for biological applications such as cell process intervention and treatment for neurodegenerative diseases.
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Artificial sensory afferent nerves that emulate receptor nanochannel perception and synaptic ionic information processing in chemical environments are highly desirable for bioelectronics. However, challenges persist in achieving life-like nanoscale conformal contact, agile multimodal sensing response, and synaptic feedback with ions. Here, a precisely tuned phase transition poly(N-isopropylacrylamide) (PNIPAM) hydrogel is introduced through the water molecule reservoir strategy. The resulting hydrogel with strongly cross-linked networks exhibits excellent mechanical performance (â¼2000% elongation) and robust adhesive strength. Importantly, the hydrogel's enhanced ionic conductance and heterogeneous structure of the temperature-sensitive component enable highly sensitive strain information perception (GFmax = 7.94, response time â¼ 87 ms), temperature information perception (TCRmax = -1.974%/°C, response time â¼ 270 ms), and low energy consumption synaptic plasticity (42.2 fJ/spike). As a demonstration, a neuromorphic sensing-synaptic system is constructed integrating iontronic strain/temperature sensors with fiber synapses for real-time information sensing, discrimination, and feedback. This work holds enormous potential in bioinspired robotics and bioelectronics.
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Facile synthesis and characterisation of three natural compounds and their two synthetic analogues based on onion skin content were performed. Both OSE and 2,4,6-trihydroxyphenylglyoxylic acid was induced effect on cell proliferation during barley germination with a difference of approximately %4 compared to the control group.
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OBJECTIVE: Emerging work suggests that affect regulation strategies (e.g., active coping, anger expression) predict disease and mortality risk, with sometimes divergent estimates by sex or education levels. However, few studies have examined potential underlying biological mechanisms. This study assessed the longitudinal association of affect regulation with future allostatic load. METHOD: In 2004-2006, 574 participants from the Midlife in the United States study completed validated scales assessing use of nine general and emotion-specific regulatory strategies (e.g., denial, anger expression). As a proxy for how flexibly participants regulate their affect, variability in the use of regulatory strategies was operationalized using a standard deviation-based algorithm and considered categorically (i.e., lower, moderate, greater variability) to assess non-linear effects. Participants also provided data on relevant covariates and 24 allostatic load biomarkers (e.g., cortisol, blood pressure). In 2017-2021, these biomarkers were again collected. Linear regressions modeled betas (ß) and 95â¯% confidence intervals (CI) examining associations of affect regulatory constructs with future allostatic load. RESULTS: In fully-adjusted models including initial allostatic load, general regulatory strategies were unrelated to future allostatic load. Yet, greater versus moderate affect regulation variability levels predicted lower allostatic load (ß=-0.14; 95â¯%CI: -0.27, -0.01). Only among more educated participants, greater use of anger expression predicted lower allostatic load, while the reverse was noted with anger control (ßexpression=-0.12; 95â¯%CI: -0.20, -0.05; ßcontrol=0.14; 95â¯%CI: 0.05, 0.24). CONCLUSIONS: While general regulatory strategies appeared unrelated to allostatic load, greater variability in their use and anger-related strategies showed predictive value. Subsequent studies should examine these associations in larger, more diverse samples.
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BACKGROUND: Maternal childhood maltreatment (CM) has been repeatedly associated with negative offspring's emotional outcomes. The dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis has emerged as the main underlying physiological mechanism. OBJECTIVE: To explore the association between maternal CM and newborns' physiological and neurobehavioral stress responses, considering the role of perinatal maternal depression and bonding. PARTICIPANTS AND SETTING: 150 healthy women were followed throughout pregnancy. 79 mother-infant dyads were included in the final analyses. Maternal CM was evaluated using the Childhood Trauma Questionnaire and depressive symptoms by the Edinburgh Postnatal Depression Scale (EPDS) at each trimester. At 7 weeks postpartum, the EPDS and the Postpartum Bonding Questionnaire were administered. Newborns' behavioral responses were assessed using "States Organization" (SO) and "States Regulation" (SR) subdomains of the Neonatal Behavioral Assessment Scale (NBAS). Newborns' salivary samples were collected before and after the NBAS to study cortisol reactivity. METHODS: A cross-lagged panel model was employed. RESULTS: Infants born to mothers with higher CM presented more optimal scores on SO (ß (0.635) = 0.216, p ã001) and SR (ß (0.273) = 0.195, p = .006), and a higher cortisol reactivity after NBAS handling (ß(0.019) = 0.217, p = .009). Moreover, newborns of mothers with higher CM and postpartum depressive symptoms exhibited a poorer performance on SR (ß (0.156 = -0.288,p = .002). Analyses revealed non-significant relationships between mother-infant bonding, newborns' cortisol reactivity and SO. CONCLUSIONS: Newborns from mothers with greater CM present higher cortisol reactivity and more optimal behavioral responses, which may reflect a prenatal HPA axis sensitization. However, those exposed to maternal postnatal depressive symptoms present poorer stress recovery.
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Despite the growing concerns about pesticide pollution, a comprehensive global understanding continues to be hampered by a lack of data from less developed countries. Ethiopia, being a typical agricultural country, is one of the top consumers of pesticides in sub-Saharan Africa. This study conducted a nationwide analysis to assess pesticide water pollution and human health risks in Ethiopia based on the available data. Additionally, the study evaluated the effectiveness of the Pesticide Risks in the Tropics for Man, Environment, and Trade (PRIMET) model, which is currently used for pesticide regulatory risk assessment in Ethiopia. The scoring approach was employed to map the site-specific pollution status based on clearly defined individual pesticide concentrations, excluding mixtures (n = 99). The pollution scores varied significantly among sites, with higher scores observed in the Rift Valley region. Acute and chronic health risks were identified for some commonly detected pesticides at their maximum concentrations. Epidemiological studies conducted in Ethiopia also demonstrated that pesticide exposure is associated with acute poisoning, respiratory health problems, neurobehavioral symptoms, and breast cancer. Furthermore, the study found that the existing regulatory framework likely underestimates pesticide risks in 35 % of the cases, raising concerns about the reliability of the PRIMET model in its current version. Overall, the results emphasize the need for increased attention to pesticide regulation and management in Ethiopia and other countries with similar scenarios, including regular monitoring, implementation of residue limits, post-application evaluations, and recalibration of the PRIMET model. This study provides valuable scientific information and insights into pesticide pollution and can serve as a baseline for ensuring agricultural and environmental sustainability.
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Indonesia is suspected as one of the largest plastic waste contributors to the ocean, resulting in microplastic (MP) contamination of the marine environment. Likewise, >250 MP research in Indonesia have been published in the last decade, including review articles. However, a comprehensive review covering MP observations in all areas, i.e. land, freshwater, and ocean, and the regulation aspect in Indonesia remains unexplored. This review finds that the current MP studies are not sufficient to provide the big picture of MP distribution in Indonesia, suggesting the need for research guidelines and coordination among scholars in this field. In addition, the currently implemented local regulation in plastic item limitation should be supported by effective monitoring, sanction, and education for citizens, as well as investment in waste management facilities. Overall, this review suggests the improvement of MP studies and national regulation as countermeasures for MP pollution problems.
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In Mexico, it is not known which institutions use animals for scientific purposes. This work reports, based on data requested from the National Institute of Transparency, Access to Information and Protection of Personal Data (INAI), the types of institutions that use animals for research and how many of these have an ethics committee. Research centres, colleges, hospitals, national institutes, technical colleges, and public universities are the types of institutions that report using animals for experimentation. Only 54% of institutions have ethics committees. Mexican institutions from 2015 to 2021 used a total of 2,112,786 animals. Mammals are the most widely used animal group. The scientific purposes for using animals depend on the type of institution that uses them. In Mexico, it is necessary to update the regulations in order to regulate the use, protection and the care of laboratory animals.
En México se desconoce cuáles son las instituciones que utilizan animales con fines científicos. Se reporta, a partir de datos solicitados al Instituto Nacional de Transparencia, Acceso a la Información y Protección de Datos Personales (INAI), los tipos de instituciones que usan animales y cuántas poseen un comité interno para el cuidado y uso de los animales de laboratorio. Los centros de investigación, colegios, hospitales, institutos nacionales, tecnológicos y universidades públicas son los tipos de instituciones que reportaron usar animales. El 54% de las instituciones poseen comités de ética. Un total de 2,112,786 animales fueron usados por instituciones del 2015 al 2021. Los mamíferos es el grupo animal más utilizado. El uso de los animales se encuentra en función del tipo de institución que los utiliza. En México, es necesario actualizar la normatividad, con el fin de regular el uso, la protección y el cuidado de los animales de laboratorio.
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Experimentação Animal , México , Animais , Experimentação Animal/ética , Animais de Laboratório , Universidades , HumanosRESUMO
INTRODUCTION: P. pastoris is a common host for effective biosynthesis of heterologous proteins as well as small molecules. Accurate regulation of gene transcription and protein synthesis is necessary to coordinate synthetic gene circuits and optimize cellular energy distribution. Traditional methanol or other inducible promoters, natural or engineered, have defects in either fermentation safety or expression capacity. The utilization of chemical inducers typically adds complexity to the product purification process, but there is no other well-controlled protein synthesis system than promoters yet. OBJECTIVE: The study aimed to address the aforementioned challenges by constructing light-regulated gene transcription and protein translation systems with excellent expression capacity and light sensitivity. METHODS: Trans-acting factors were designed by linking the N. crassa blue-light sensor WC-1 with the activation domain of endogenous transcription factors. Light inducible or repressive promoters were then constructed through chimeric design of cis-elements (light-responsive elements, LREs) and endogenous promoters. Various configurations of trans-acting factor/LRE pairs, along with different LRE positions and copy numbers were tested for optimal promoter performance. In addition to transcription, a light-repressive translation system was constructed through the "rare codon brake" design. Rare codons were deliberately utilized to serve as brakes during protein synthesis, which were switched on and off through the light-regulated changes in the expression of the corresponding pLRE-tRNA. RESULTS: As demonstrated with GFP, the light-inducible promoter 4pLRE-cPAOX1 was 70â¯% stronger than the constitutive promoter PGAP, with L/D ratioâ¯=â¯77. The light-repressive promoter PGAP-pLRE was strictly suppressed by light, with expression capacity comparable with PGAP in darkness. As for the light-repressive translation system, the "triple brake" design successfully eliminated leakage and achieved light repression on protein synthesis without any impact on mRNA expression. CONCLUSION: The newly designed light-regulated transcription and translation systems offer innovative tools that optimize the application of P. pastoris in biotechnology and synthetic biology.
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Regulatory efforts are hypothesized to affect associations between emotions and physiology (i.e., concordance) to facilitate adaptive functioning. Assessing the role of coping on physiological-emotional concordance during ecologically relevant scenarios can elucidate whether concordance can serve as a biomarker of risk or resilience. The present study assessed self-reported coping as a moderator of minute-to-minute associations between autonomic nervous system activity and emotions (i.e., physiological-emotional concordance) in caregivers (N = 97) and adolescents (N = 97; ages 10-15) during a dyadic conflict task. Models included physiological variables (sympathetic, skin conductance level [SCL]; and parasympathetic, respiratory sinus arrhythmia [RSA]) and their interaction (SCL × RSA) as predictors of emotions, with coping variables as moderators. Caregivers' use of primary control coping (e.g., problem solving and emotional expression) and secondary control coping (e.g., cognitive reappraisal and acceptance) use in response to family stress predicted more positive emotional experiences during the laboratory conflict task. Adolescents' use of secondary control coping moderated the SCL-emotion association, such that increases in momentary SCL were associated with more positive emotion ratings for youth reporting higher secondary control coping. For youth who report more adaptive trait-level coping skills, momentary changes in SCL may reflect active engagement and attentiveness to facilitate more positive emotional experiences. Findings advance our understanding of the interrelationships between physiological responses and psychological experiences during relevant, interactive scenarios. Autonomic responses are differentially related to affective states depending on the coping strategies that adolescents employ, suggesting that concordance may be associated with intervention targets (i.e., coping skills).
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The ability to sense and respond effectively to acidic stress is important for microorganisms to survive and proliferate in fluctuating environments. As specific metabolic activities can serve to buffer the cytoplasmic pH, microorganisms re-wire their metabolism to favour these reactions and thereby mitigate acid stress. The orally-acquired pathogen Listeria monocytogenes exploits alternative metabolic activities to overcome the acidic stress encountered in the human stomach or food products. In this minireview, we discuss the metabolic processes in L. monocytogenes that mitigate acid stress, with an emphasis on the proton-depleting reactions including glutamate decarboxylation, arginine/agmatine deimination, and fermentative acetoin production. We also summarize the recent findings on regulatory mechanisms that control the expression of genes that are responsible for these metabolic activities, including the general stress response regulator SigB, arginine repressor ArgR, and the recently discovered RofA-like transcriptional regulatory GadR. We further discuss the importance of this metabolic reprogramming in the context of food products and within the host. Finally, we highlight some outstanding challenges in the field including an understanding of acid-sensing mechanisms, the role of intra-species heterogeneity in acid resistance, and how a fundamental understanding of acid stress response can be exploited for food formulation to improve food safety and reduce food waste.
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BACKGROUND: Sanqi, the root of Panax notoginseng, has long been recognized for its therapeutic effects on cardiovascular diseases. Saponins, including ginsenosides and notoginsenosides, are the main bioactive components of P. notoginseng. The biosynthesis of saponins is closely related to the defense responses orchestrated by endogenous hormones. RESULTS: To provide new insights into the underlying role of phytohormone jasmonic acid (JA) in the synthesis and regulation of saponins, we performed an ultra-performance liquid chromatography analysis of different tissues of P. notoginseng aged 2-4 years. Moreover, by combined evaluation of saponin content and transcriptome profiling of each tissue, the spatial and temporal distribution of saponins was analyzed. N notoginsenoside R1, ginsenoside Rb1 and ginsenoside Rd accumulated in the underground tissues, including the root, tuqi, fibril and rhizome. In agreement with this data, the corresponding genes of the endogenous hormone JAs, especially coronatine insensitive 1 (COI1) and myelocytomatosis proteins 2 (MYC2), were predominantly expressed in the underground tissues. The tissue- and age-specific distribution of saponins was consistent with the expression of genes involved in JA biosynthetic, metabolic and signaling pathways. CONCLUSION: The present study has revealed the temporal and spatial effects of endogenous phtohormones in the synthesis and regulation of notoginsenosides, which will provide a significant impact on improving the ecological planting technology, cultivating new high-quality varieties and protecting the rare resources of medicinal P. notoginseng. © 2024 Society of Chemical Industry.
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College students are at a heightened risk of experiencing depression and anxiety symptomatology and engaging in maladaptive alcohol use. Understanding how alcohol interventions impact emotional functioning is essential. One such intervention uses Deviance Regulation Theory (DRT), which posits that behavior can be modified using targeted messaging as a function of perceived norms. DRT has been shown to be effective at increasing responsible drinking behaviors and decreasing alcohol-related consequences. However, it is unclear if this intervention influences emotional functioning. The current examines the impact of a DRT intervention on emotional functioning. Participants (n = 147) were recruited from a large Southeastern university. The study included a screening phase, intervention, and six-week follow-up. Participants were randomly assigned to one of three conditions: a positive message condition about people who drink responsibly, a negative message condition about people who do not drink responsibly, and an active control condition. During the study, all participants reported on depression/anxiety symptoms, alcohol use, responsible drinking, and alcohol-related consequences. Mixed-effects regression was used to analyze the data. Results suggest an overall reduction of depressive and anxiety symptomatology in the intervention conditions but not in the control condition. In the positive condition, there was a decrease in depressive and anxiety symptomatology. The messaging was not moderated by normative beliefs. The negative condition also led to decreases in depression and anxiety symptomatology over time. In addition, perceived norms moderated the negative message in the first week after the intervention, an effect consistent with DRT. Prior research indicates this intervention is efficacious for the reduction of adverse alcohol outcomes; these data show that the intervention may also have positive effects on downstream mental health outcomes.
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Ras signaling and glycosylphosphatidylinositol (GPI) biosynthesis are mutually inhibitory in S. cerevisiae (Sc). The inhibition is mediated via an interaction of yeast Ras2 with the Eri1 subunit of its GPI-N-acetylglucosaminyl transferase (GPI-GnT), the enzyme catalyzing the very first GPI biosynthetic step. In contrast, Ras signaling and GPI biosynthesis in C. albicans (Ca) are mutually activated and together control the virulence traits of the human fungal pathogen. What might be the role of Eri1 in this pathogen? The present manuscript addresses this question while simultaneously characterizing the cellular role of CaEri1. It is either nonessential or required at very low levels for cell viability in C. albicans. Severe depletion of CaEri1 results in reduced GPI biosynthesis and cell wall defects. It also produces hyperfilamentation phenotypes in Spider medium as well as in bicarbonate medium containing 5% CO2, suggesting that both the Ras-dependent and Ras-independent cAMP-PKA pathways for hyphal morphogenesis are activated in these cells. Pull-down and acceptor-photobleaching FRET experiments suggest that CaEri1 does not directly interact with CaRas1 but does so through CaGpi2, another GPI-GnT subunit. We showed previously that CaGpi2 is downstream of CaEri1 in cross talk with CaRas1 and for Ras-dependent hyphal morphogenesis. Here we show that CaEri1 is downstream of all GPI-GnT subunits in inhibiting Ras-independent filamentation. CaERI1 also participates in intersubunit transcriptional cross talk within the GPI-GnT, a feature unique to C. albicans. Virulence studies using G. mellonella larvae show that a heterozygous strain of CaERI1 is better cleared by the host and is attenuated in virulence.
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The maturation of effective emotion regulation (ER) skills is a core achievement of adolescence and youth are now developing their ER habits and skills in a hybrid reality of digital and non-digital experiences. We present a new model of adolescent digital emotion regulation as a conceptual framework to help guide burgeoning research in this area. We distinguish two primary processes: the regulation of emotions that have been elicited within digital contexts (i.e., the regulation of digitally induced emotions), and how youth regulate their emotions through digital means (i.e., digitally regulated emotion). Following the explication of different pathways in the model and consideration of the affordances of digital contexts, we highlight how this framework connects to theory and guides future research.
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Fluorogens with aggregation-induced emission (AIEgens) are promising agents for two-photon fluorescence (TPF) imaging. However, AIEgens' photophysical properties are fixed and unoptimizable once synthesized. Therefore, it is urgent and meaningful to explore an efficient post-regulation strategy to optimize AIEgens' photophysical properties. Herein, a general and efficient post-regulation strategy is reported. By simply tuning the ratio of inert AIEgens within binary nanoparticles (BNPs), the fluorescence quantum yield and two-photon absorption cross-section of functional AIEgens are enhanced by 8.7 and 5.4 times respectively, which are not achievable by conventional strategies, and the notorious phototoxicity is almost eliminated. The experimental results, theoretical simulation, and mechanism analysis demonstrated its feasibility and generality. The BNPs enabled deep cerebrovascular network imaging with ≈1.10 mm depth and metastatic cancer cell detection with single-cell resolution. Furthermore, the TPF imaging quality is improved by the self-supervised denoising algorithm. The proposed binary molecular post-regulation strategy opened a new avenue to efficiently boost the AIEgens' photophysical properties and consequently TPF imaging quality.
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INTRODUCTION: Relational regulation theory describes how social network members (providers of regulation) help people (recipients of regulation) regulate their effect, actions and thoughts through mostly ordinary social interaction. Regulation is relational when the ability of a provider to regulate a recipient is an emergent property of the dyad and not a stable property of the provider or recipient. Research in predominantly well samples has found that dyads evoked affect and self-relevant thought in recipients. The present research examined whether such effects occurred among people with probable major depressive disorder (MDD). METHODS: A national, internet sample of 2058 US residents was screened for probable MDD. Depressed recipients (N = 152) rated their experience of depression-related constructs when with or thinking about specific providers. RESULTS: Recipients' reports of affect and thought varied strongly depending on the dyad they were with or thinking about. These effects occurred for depressive symptoms, positive and negative affect, self-esteem, negative automatic thoughts, hopelessness, excessive reassurance-seeking, reappraisal and emotion suppression. Dyads that evoked depression-related experiences were seen by participants as unsupportive and as evoking conflict. CONCLUSION: Relational regulation appears to occur among people with MDD which provides new insights about interpersonal processes in depression.
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Reprogramming tumor-associated macrophages (TAMs) to an inflammatory phenotype effectively increases the potential of immune checkpoint blockade (ICB) therapy. Artificial mitochondrial transplantation, an emerging and safe strategy, has made brilliant achievements in regulating the function of recipient cells in preclinic and clinic, but its performance in reprogramming the immunophenotype of TAMs has not been reported. Here, the metabolism of M2 TAMs is proposed resetting from oxidative phosphorylation (OXPHOS) to glycolysis for polarizing M1 TAMs through targeted transplantation of mannosylated mitochondria (mPEI/M1mt). Mitochondria isolated from M1 macrophages are coated with mannosylated polyethyleneimine (mPEI) through electrostatic interaction to form mPEI/M1mt, which can be targeted uptake by M2 macrophages expressed a high level of mannose receptors. Mechanistically, mPEI/M1mt accelerates phosphorylation of NF-κB p65, MAPK p38 and JNK by glycolysis-mediated elevation of intracellular ROS, thus prompting M1 macrophage polarization. In vivo, the transplantation of mPEI/M1mt excellently potentiates therapeutic effects of anti-PD-L1 by resetting an antitumor proinflammatory tumor microenvironment and stimulating CD8 and CD4 T cells dependent immune response. Altogether, this work provides a novel platform for improving cancer immunotherapy, meanwhile, broadens the scope of mitochondrial transplantation technology in clinics in the future.