Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacological targeting of NLRP3 deubiquitination for treatment of NLRP3-associated inflammatory diseases

Thiolutin, an inhibitor of the BRISC deubiquitinating enzyme complex, specifically and potently inhibits NLRP3 inflammasome activation. DUBbing new inflammasome inhibitors Inflammasome assembly and activation leading to mature IL-1β release is dysregulated in a wide range of inflammatory diseases. Optimal activation of the NLRP3 inflammasome requires the activity of BRISC, a deubiquitinating enzyme (DUB) complex composed of four protein subunits including BRCC3. Ren et al. demonstrate that the compound thiolutin, a zinc chelator that inhibits JAMM domain–containing metalloproteases including BRCC3, can potently inhibit NLRP3 deubiquitination and inflammasome activation. Thiolutin was effective at inhibiting NLRP3 activation and preventing IL-1β production in multiple mouse models of inflammatory disease, including a model of diet-induced nonalcoholic fatty liver disease. Holomycin, a derivative of thiolutin with reduced toxicity, was also effective at inhibiting NLRP3, paving the way to develop novel agents that selectively target deubiquitination of NLRP3 to regulate its activity. Pharmacologically inhibiting nucleotide-binding domain and leucine-rich repeat-containing (NLR) family, pyrin domain–containing protein 3 (NLRP3) inflammasome activation results in potent therapeutic effects in a wide variety of preclinical inflammatory disease models. NLRP3 deubiquitination is essential for efficient NLRP3 inflammasome activity, but it remains unclear whether this process can be harnessed for therapeutic benefit. Here, we show that thiolutin (THL), an inhibitor of the JAB1/MPN/Mov34 (JAMM) domain–containing metalloprotease, blocks NLRP3 inflammasome activation by canonical, noncanonical, alternative, and transcription-independent pathways at nanomolar concentrations. In addition, THL potently inhibited the activation of multiple NLRP3 mutants linked with cryopyrin-associated periodic syndromes (CAPS). Treatment with THL alleviated NLRP3-related diseases in mouse models of lipopolysaccharide-induced sepsis, monosodium urate–induced peritonitis, experimental autoimmune encephalomyelitis, CAPS, and methionine-choline–deficient diet-induced nonalcoholic fatty liver disease. Mechanistic studies revealed that THL inhibits the BRCC3-containing isopeptidase complex (BRISC)–mediated NLRP3 deubiquitination and activation. In addition, we show that holomycin, a natural methyl derivative of THL, displays an even higher inhibitory activity against NLRP3 inflammasome than THL. Our study validates that posttranslational modification of NLRP3 can be pharmacologically targeted to prevent or treat NLRP3-associated inflammatory diseases. Future clinical development of derivatives of THL may provide new therapies for NLRP3-related diseases.
Do we prioritise memory for cheaters? Rebuttal evidence from old/new effects in episodic memory

ABSTRACT Behavioural investigations concerning the influence of cooperation and cheating on the two sub-types of episodic memory (i.e. item memory and source memory), especially on source memory, have shown inconsistent patterns. Besides, the sensitivity of retrieval-relevant neural activities to cooperation and cheating is rarely explored. To delve into these issues, the current study investigated how cooperation and cheating affected old/new effects in item memory and source memory. The results demonstrated that both types of memory elicited four-stage retrieval-relevant processes, indexed by FN400, LPC, LPN, and RFE, respectively. There was moderate to strong evidence that LPC, LPN, and RFE were insusceptible to cooperation and cheating. For the familiarity-based FN400, in item memory, the effect was only identified in the cooperative condition, while in source memory, there was moderate evidence that the effect was comparable between the cooperative and the cheating circumstances. The above data provide no psychophysiological evidence for the cheater-detection strategy.
Belonging and loneliness in cyberspace: impacts of social media on adolescents’ well-being

ABSTRACT Objectives: The rapidly shifting landscape of social media technology presents challenges to researchers and clinicians attempting to understand the impact of such technology on individuals’ psychosocial development. In this paper, we provide a historical perspective on research exploring the relationship between social media use and loneliness and belonging among adolescents and young adults. Method: Rather than attempting an exhaustive review of literature in this area, we provide a narrative review on the evolution of social media technology over the past 20 years and its impact on socialization experiences of adolescents and young adults. Results: Our narrative review, based on three prominent theoretical models in the field, reveals somewhat divergent findings, which may, to a large extent, reflect the remarkable evolution over the past few years in how youths use communication media technology. In this review, we consider individual, societal, and cultural factors that may explain preferences for various forms of online communication and related social outcomes such as belonging and loneliness. Conclusions: Rather than asking whether social media involvement leads to feelings of loneliness and isolation for youth or opens a new frontier for connectedness and belonging, a more useful question is under what circumstances and for whom do these outcomes occur. Social media technology can be both a deterrent and a boost to youths’ sense of social well-being, depending on the nature of its use. We provide some cautions and guidelines for utilizing social media to promote psychological well-being among youth.
School belongingness, well-being, and mental health among adolescents: exploring the role of loneliness

ABSTRACT Objective: Within the school context, the need to belong is a fundamental psychological construct associated with a variety of important adolescent school‐based and quality‐of‐life outcomes. The objective of the present study is to investigate the mediating effect of loneliness on the association between school belonging constructs (i.e., social inclusion and exclusion) and subjective well‐being and mental health problems among adolescents. Method: Participants of this study included 244 adolescents in grades 9–12 attending a high school in a city of Turkey. They were comprised of 52.5% female and 47.5% male and ranged in age between 14 and 18-years (M = 16.27, SD = .1.02). Results: Findings of the study indicated that school‐based social inclusion and exclusion significantly predicted loneliness, mental health problems, and subjective well‐being. Mediation analyses showed that loneliness partially mediated the relationship of social inclusion with mental health problems and subjective well‐being. Thereafter, loneliness had a full mediating effect on the association between social exclusion and subjective well‐being and partially mediated the effect of social exclusion on adolescent mental health problems. Social inclusion and exclusion also indirectly predicted mental health problems through subjective well‐being. Conclusion: Findings of this study suggest that loneliness is an important mechanism that may help to explain the effect of school belongingness on adolescent well‐being and mental health. The results highlight the importance of school belongingness‐based preventions and interventions targeting to promote mental health and well‐being in school settings. KEY POINTS What is already known about this topic: Belongingness is an important psychological construct for mental health and well‐being, not only at an empirical level but also at a theoretical level. A satisfied need for belonging improves youth well‐being and mental health, whereas unsatisfied or lack of this need can lead to a variety of psychosocial problems, such as loneliness. Loneliness has adverse impacts on adolescent well‐being and is a risk factor for developing emotional and behavioural problems What this topic adds: The present study highlights the importance of school belongingness‐based preventions and interventions targeting to promote mental health and well‐being in school settings. Loneliness is an important mechanism that may help to explain the effect of school belongingness on well‐being and mental health of adolescents. The study outcomes suggest there is a need to design a more comprehensive prevention and intervention approach for improving adolescent mental health and well‐being.
A review of the criteria for non-invasive diagnosis of cardiac transthyretin amyloidosis

ABSTRACT Introduction: Cardiac transthyretin (ATTR) amyloidosis is a progressive and fatal infiltrative cardiomyopathy (ATTR-CM) characterized by congestive cardiac failure, often with preserved left ventricular ejection fraction, and significant risk of conduction disease. Diagnosis is often delayed or missed due to poor specificity of echocardiography and the historical requirement for a histological diagnosis, frequently an endomyocardial biopsy. Areas covered: Following a detailed literature review focusing on peer reviewed articles (Pubmed, Cochrane Library, Google Scholar), from 1995 to 2020, alongside international diagnostic guidelines and expert opinion in the field, this article will explore the current non-invasive diagnostic criteria for ATTR-CM including the role of transthoracic echocardiography, cardiac MRI, bone scintigraphy, and assessment for exclusion of a clonal dyscrasia. Expert opinion: ATTR-CM is an emerging and increasingly diagnosed cause of heart failure, particularly in the elderly. Promising novel therapies make accurate and swift diagnosis of the disease vital. With the increasing use of cardiac MRI to investigate cardiomyopathy and repurposing of technetium-labeledbone scintigraphy, clinicians are now often able to diagnose ATTR-CM without recourse to an endomyocardial biopsy.
Employment incongruity and gender among Middle Eastern and North African skilled migrants in Australia

ABSTRACT We investigate ‘employment incongruity’ among skilled migrants from Middle Eastern and North African (MENA) countries – that is, whether the jobs they achieve in Australia match the jobs they expect to be doing after they arrive or not – along with the factors that shape outcomes and the gendered dimensions of these outcomes. We analyse data collected from qualitative interviews with 15 females and eight male skilled MENA migrants, a median of seven years after arrival and apply an intersectionality lens and consider influences at the macro, meso and micro level that affect the power of female MENA migrants and shape their employment outcomes. We identify that what appears to shape employment incongruity are: organisational practices regarding recognition of overseas qualifications and demands for ‘local experience’; norms supporting discriminatory behaviour; the difficulties skilled MENA migrants have with accessing networks; and intra-family cultural norms. These findings are significant for current and future skilled MENA migrants, with the employment outcomes of most of the participants in this study revealing a mismatch between government immigration policies and organisational practices.
The relationship of student-to-student confirmation in the classroom to college students’ mental health and well-being

ABSTRACT The purpose of this study was to examine the impact of student-to-student confirmation on college students’ self-reported mental health and well-being. It was proposed that confirming messages work to reduce indicators of mental illness (i.e., depression, stress, and anxiety), which in turn affect students’ mental health (i.e., psychological well-being). College students (N = 412) completed a survey questionnaire. Results of correlational and mediation analyses indicate that student-to-student confirmation is related to psychological well-being as well as indicators of mental illness (i.e., depression). Self-reported depression symptoms mediated the relationship between all three dimensions of student-to-student confirmation and psychological well-being. This study contributes to the growing conversation of college student mental health and its relation to the teaching-learning process, as well as contributing to the theoretical understanding of confirmation in the college classroom.
Effect of lactic acid bacteria administered as feed supplement on the weight gain and ruminal pH in two South African goat breeds

Antibiotics as growth promoters are banned in most European countries, because of antibiotic resistance and residues in animal products, and the release of recalcitrant antibiotics into the environment. Probiotics are the preferred alternative, because of no harmful attributes when compared to antibiotics, and the additional advantage of the ability to stabilise the microbial communities in the gut. We investigated the effects of LAB on the growth performance of South African goats. Randomly selected 17 Specked and 18 Boer goats were divided into five treatment groups according to sex and breed and were placed in an experimental trial for 30 days. Ruminal fluid was collected before and after the trial to monitor the changes in the pH. Data collected were analysed using a one-way analysis of variance (ANOVA) (SAS, version 9.4). Results revealed that LAB supplementation had no effect on feed intake in all experimental groups. However, the average weight gain was higher in the LAB groups when compared to other groups. Sex and breed had effects on final body weight; that is male (18.4 kg) goats are heavier than females (15.3 kg) averagely, irrespective of the breed, and the Boer goats are heavier than Specked irrespective of gender. The pH decreased averagely from 7.01 to 6.33 across all treatments, confirming the modulatory effect of the administered lactic acid bacteria. The findings in this study suggested that LAB as probiotics may induce beneficial effects in goats by enhancing weight gain, dropping the gut pH, thus maintaining an equilibrium of ruminal microbiota.
Tecido-não-tecido (TNT) para ensacamento de cachos visando controle de broqueadores de frutos do tomateiro (Solanum lycopersicum L.)

O tomateiro e atacado por insetos-praga durante todo seu ciclo e, dentre os quais, destacam-se os artropodes-broqueadores de frutos. O objetivo do trabalho foi avaliar a eficiencia do uso de TNT para o ensacamento de flores e/ou frutos de tomate ‘Valerin’ como controle mecânico dos broqueadores de frutos avaliando os indicadores agronomicos da cultura, a qualidade pos-colheita dos frutos, a relacao custo/beneficio, bem como, o melhor periodo para realizacao do ensacamento. O ensaio foi conduzido em plantio comercial de tomateiro estaqueado, localizado no municipio de Ubajara, Ceara, Brasil em delineamento experimental de blocos casualizados em esquema fatorial 2 x 4 com cinco repeticoes. Os fatores considerados foram duas formas de utilizacao de inseticidas para controle de broqueadores [1- Plantas tratadas com inseticidas; e 2- Plantas nao tratadas com inseticidas] e quatro periodos de ensacamento dos cachos com TNT [T1- Ensacamento da flor; T2- Ensacamento do cacho com frutos de 1,5 cm; T3- Ensacamento do cacho com frutos de 3,0 cm; e Cachos nao ensacados (testemunha)]. Os parâmetros avaliados foram: Numero de frutos/cacho, numero de cachos/planta, peso dos frutos (Kg), diâmetro longitudinal (cm), diâmetro transversal (cm), incidencia de insetos broqueadores (%), produtividade (ton/ha), perda provocada pelo ataque das pragas (ton/ha), ganho real obtido (ton/ha), custo/beneficio de implantacao, acidez titulavel, solidos soluveis totais, coloracao dos frutos (Luminosidade, cromaticidade, ângulo hue), firmeza dos frutos, carotenoides totais, licopeno e s-caroteno. As analises pos-colheita foram realizadas no Laboratorio de Pos-Colheita da Embrapa Agroindustria Tropical. O uso de TNT no ensacamento dos cachos/frutos de tomate ‘Valerin’ nao interferiu no desempenho produtivo e na qualidade pos-colheita dos frutos. O custo medio para o ensacamento dos frutos com sacos TNT foi cerca de 40,7% inferior ao necessario para o controle quimico. Nao foi observada a presenca de Tuta absoluta (Lepidoptera: Gelechiidae), Helicoverpa zea e Helicoverpa armigera (Lepidoptera: Noctuidae) durante as avaliacoes, no entanto, o ensacamento dos cachos de tomate ‘Valerin’ com TNT quando os frutos apresentavam 1,5 cm de diâmetro foi mais eficaz para o controle de Neoleucinodes elegantalis (Lepidoptera: Crambidae), promoveu incremento de 21,5% na produtividade final em relacao aqueles nao ensacados e nao comprometeu a qualidade pos-colheita dos frutos, sendo, portanto, considerado o melhor periodo para a realizacao do ensacamento.
Playing and Digital Reality: Treating Kids and Adolescents in a Pandemic

The COVID-19 pandemic forced therapists and patients to physically separate and conduct sessions from afar. This created particular challenges for child and adolescent work, which tends to center around movement and embodiment. As therapists navigated the constraints of their new reality, early skepticism quickly gave way to creative, on-the-spot solutions. Born out of necessity, therapist’s flexibility and accommodations brought about changes to the analytic frame that were unprecedented in scope. Common themes include the therapist’s loss of control over the structure of psychotherapy, a renegotiation of therapist and patient roles, placing the parent at the center of treatment, findings new ways to play, and virtual treatment as a new mechanism for modulating closeness and intimacy in the therapeutic dyad. Rooted in clinical vignettes of clinicians from the early weeks of the pandemic, this paper will illustrate these themes and consider their implications for the future of psychotherapy with children and adolescents.
Evaluating the potential of Bacillus subtilis fermented okara as a functional food ingredient through in vitro digestion and fermentation

ABSTRACT In this study, in vitro digestion and fermentation was employed to simulate the consumption of fermented okara and hence, evaluate its potential as a functional food ingredient. This is to develop a method of utilizing okara without producing secondary waste. Fermentation increased the amount of soluble dietary fiber by 187%. Bioaccessibility of amino acids, fatty acids, and vitamin K2 MK-7 is higher in the digestion supernatant of fermented okara. Bacillus subtilis also remained viable after digestion. Supernatants of fermented okara exhibited higher bio accessibility of total phenolic content and higher DPPH radical scavenging activity in the small and large intestines. Similarly, the concentrations of acetic acid, propionic acid, and butyric acid were 44.4%, 46.9%, and 51.8% higher, respectively. The gut microbiota was also found to be different in the fermentation supernatants between fermented and unfermented okara. Results demonstrated the potential of fermented okara as a functional food ingredient.
The impact of indicator selection on assessment of global greening

ABSTRACT Greening represents a significant increase in vegetation activity. Accurate quantification of global greening in peak growth is vital for quantifying changes in terrestrial productivity. Normalized Difference Vegetation Index (NDVI) is the remote sensing indicator most commonly applied for this purpose. However, there is limited knowledge about how the applications of other improved or newly available products can impact global greening assessments. This study reports the first systematic investigation of the impact of vegetation indicator selection on global greening in peak growth. It examines the period from 2003 to 2017 using six indicators with a spatial resolution of 500 m: Near Infrared Reflectance of terrestrial vegetation (NIRv) and the coupled diagnostic biophysical modeled Gross Primary Production (PML-GPP), together with NDVI, Enhanced Vegetation Index with two bands (EVI2), Leaf Area Index (LAI) and Moderate Resolution Imaging Spectroradiometer (MODIS) GPP (MOD-GPP) calculated based on MODIS images. Vegetation trends were estimated using the Mann–Kendall test, the unanimous trends by six vegetation indicators were derived, and the concordance ratio in estimated trends by each pair of indicators was investigated among different biomes and their sensitivity to changes in climate were investigated. We found that the estimated greening and browning varied between 12–23% and 2–13% of the vegetated areas, respectively. There was more net greening estimated from NDVI and MOD-GPP (around 19%) compared to the other indicators (8–11%). The concordance ratio between EVI2 and NIRv was much higher (>94%) than other combinations (61–76%) at the global scale. The concordance ratio between one specific indicator and the other indicators gradually increased with its change magnitude. Unanimous results from these six indicators were exhibited in less than two-fifths (38.71%) of vegetated areas. Apart from the EVI2 and NIRv, the concordance ratio varied among different biomes: high in cropland (67–81%), but low in deciduous needle-leaf forest (51–62%) and very low in evergreen broadleaf forest between PML-GPP and others (37–49%). The diverse sensitivity to changes in climate contributed to the discrepancies: greening was more pronounced during warming conditions for the GPP products when compared with the greenness indices. At the global scale, the concordance ratio was higher during cooling conditions among all the indicators except between PML-GPP. Datasets supporing these findings are available online at https://github.com/FuzhouSIRC/Greening_6indicators. 2
A novel strain of Yarrowia phangngaensis producing a multienzyme complex; a source of enzyme additives for baking high cassava-wheat composite bread

ABSTRACT The current research focused on the isolation of a yeast strain possessing an enzyme complex for use in baking high quality, high cassava-wheat composite bread. Yeast isolates were obtained from soil, fruit and wine samples and screened for the ability to synthesize lipase, cellulase, xylanase, pectinase, amylase and protease. Enzyme cocktails from four selected isolates were used for baking 50/50% cassava/wheat composite bread. Quality assessment was based on the baked product that gave the highest specific volume and acceptability rating when compared to 100% wheat bread. Enzyme cocktail from isolate C18, identified as Yarrowia phangngaensis XB3 gave the best results. This strain grew well at 24ºC and was able to ferment glucose, maltose, and galactose. Fatty acid methyl ester analysis showed that oleic acid was most abundant in its cell wall. Y. phangngaensis XB3 has the potential to serve as an enzyme source in cassava composite bread technology.