Miracle-dz/UniFAR-FTUs huggingface dataset:
Androgens improve ovarian follicle function impaired by glucocorticoids through an androgen-IGF1-FSH synergistic effect

High concentrations of glucocorticoids caused by chronic stress are known to affect ovarian function and cause diminished ovarian reserve. Androgens are essential for early-stage ovarian follicle development, but the effects and mechanisms of androgens on follicle development under chronic stress remain unclear. In this study, we aim to investigate the effects of high concentrations of glucocorticoids on the function of in vitro cultured ovarian cells and mouse early-stage ovarian follicles and to validate the hypothesis that androgen–insulin-like growth factor 1 (IGF1)–follicle-stimulating hormone (FSH) synergistic signaling helps to ameliorate the damage caused by high concentrations of glucocorticoids. KGN cells (human granulosa cell line) and mouse primary cells were treated with different concentrations of glucocorticoids, and the cell proliferation, apoptosis, and sex hormone secretion were detected. The effects of glucocorticoid and androgens on IGF1 receptor (IGF1R) and FSH receptor (FSHR) expression in KGN cells were detected by Western blot. Steroidogenic synthase expressions under androgens and androgen-IGF1-FSH combination treatment were examined by qPCR after manipulation using low and high concentrations of glucocorticoids. The mechanism of androgen regulation of IGF1R and FSHR was explored by small interfering RNA (siRNA) and chromatin immunoprecipitation (ChIP)-qPCR. Damage of glucocorticoids and the treatment effects of androgens were further validated in mouse ovarian follicles cultured in vitro. The results demonstrated that prolonged treatment with high-dose glucocorticoids reduced cell viability of granulosa cells, inhibited their sex hormone secretion, and impaired their sensitivity to IGF1 and FSH signaling by affecting IGF1R and FSHR functions. Androgens at an appropriate dose range improved early-stage follicle development and their hormone secretion under high-dose glucocorticoid treatment, which was related to increased transcription of Igf1r and Fshr. This work showed that excessive glucocorticoids impaired ovarian function and validated that balanced concentrations of androgens synergized with IGF1 and FSH to improve the function of early-stage ovarian follicles under conditions of chronic stress.
Peroxisome proliferator-activated receptor gamma and its natural agonists in the treatment of kidney diseases

Kidney disease is one of the leading non-communicable diseases related to tremendous health and economic burden globally. Diabetes, hypertension, obesity and cardiovascular conditions are the major risk factors for kidney disease, followed by infections, toxicity and autoimmune causes. The peroxisome proliferator-activated receptor gamma (PPAR-γ) is a ligand-activated nuclear receptor that plays an essential role in kidney physiology and disease. The synthetic agonists of PPAR-γ shows a therapeutic effect in various kidney conditions; however, the associated side effect restricts their use. Therefore, there is an increasing interest in exploring natural products with PPARγ-activating potential, which can be a promising solution to developing effective and safe treatment of kidney diseases. In this review, we have discussed the role of PPAR-γ in the pathophysiology of kidney disease and the potential of natural PPAR-γ agonists in treating various kidney diseases, including acute kidney injury, diabetic kidney disease, obesity-induced nephropathy, hypertension nephropathy and IgA nephropathy. PPAR-γ is a potential target for the natural PPAR-γ agonists against kidney disease; however, more studies are required in this direction.
Grievance-fueled violence can be better understood using an enactive approach

Understanding lone actor grievance-fueled violence remains a challenge. We believe that the concept of grievance provides an opportunity to add an engaged, first-person perspective to the assessment of lone actor extreme violence. We propose an enactivist philosophical approach that can help to understand the why and how of the pathway from grievance to violent extremism. Enactivism sees grievance as a dynamic, interpersonal, and context-sensitive construct that indicates how (potential) offenders make sense of the world they live in and how under certain circumstances it fuels violent behavior. Hence, grievance should not be understood as a given thing, but as an unfolding experience that involves sense-making through (regulation of one’s) interaction with the (social) environment. This (self-)relational and ecological understanding requires another approach than looking at demographic factors or life histories, only from an outsider’s perspective. Enactivism invites us to look at such risk factors as external indices of an ongoing process of active self-regulation and sense-making, and in some cases spiraling toward extreme violence. To understand the mindset of the offender we need to look more in depth at the processes that shape this mindset: why does this person, with this history, in this context, and at this point in time, proceed to use violence? The enactivist approach to the mind offers a complementary framework that may help us to understand the dynamics of grievance as a possible precursor to violent extremism. It also helps to appreciate why the relative unpredictability of the pathway toward lone actor extreme violence is not necessarily a sign of empirical weakness but a matter of principle due to the non-linearity of the processes involved. We end by summarizing how enactivism could contribute to the prevention of extremist violence and research and how it can help to avoid reinforcing stigmas and re-establishing a confirmation bias.
Driving down malaria transmission with engineered gene drives

The last century has witnessed the introduction, establishment and expansion of mosquito-borne diseases into diverse new geographic ranges. Malaria is transmitted by female Anopheles mosquitoes. Despite making great strides over the past few decades in reducing the burden of malaria, transmission is now on the rise again, in part owing to the emergence of mosquito resistance to insecticides, antimalarial drug resistance and, more recently, the challenges of the COVID-19 pandemic, which resulted in the reduced implementation efficiency of various control programs. The utility of genetically engineered gene drive mosquitoes as tools to decrease the burden of malaria by controlling the disease-transmitting mosquitoes is being evaluated. To date, there has been remarkable progress in the development of CRISPR/Cas9-based homing endonuclease designs in malaria mosquitoes due to successful proof-of-principle and multigenerational experiments. In this review, we examine the lessons learnt from the development of current CRISPR/Cas9-based homing endonuclease gene drives, providing a framework for the development of gene drive systems for the targeted control of wild malaria-transmitting mosquito populations that overcome challenges such as with evolving drive-resistance. We also discuss the additional substantial works required to progress the development of gene drive systems from scientific discovery to further study and subsequent field application in endemic settings.
The number of stable points of an infinite-range spin glass memory

A rigorous asymptotic expression for the number of stable points of an infinite-range spin glass with independently identically distributed (i.i.d) zero-mean gaussian exchange interactions is discussed. The result also applies tot he number of stable points of a Hopfield Memory (a kind of associative memory) when the memory connections are i.i. d. zero-mean gaussians. The result is that the number of stable points is asymptotic to a constant slightly larger than 1 times 2 to a power slightly larger thann/4, where n is the number of spins in the glass, or the length of the n-tuples to be remembered by the memory. The answer is easily derived using simple asymptotic techniques from an exact expression for the probability that an arbitrary plus or minus 1 n-tuple of spins is a fixed point. This expression is obtained from the fact that any distribution of joint zero-mean gaussians of given covariances is specified solely by these covariances. This is a far shorter derivation of the result than those existing.
Depth-resolved photochemical production of hydrogen peroxide in the global ocean using remotely sensed ocean color

Hydrogen peroxide (H2O2) is an important reactive oxygen species (ROS) in natural waters, affecting water quality via participation in metal redox reactions and causing oxidative stress for marine ecosystems. While attempts have been made to better understand H2O2 dynamics in the global ocean, the relative importance of various H2O2 sources and losses remains uncertain. Our model improves previous estimates of photochemical H2O2 production rates by using remotely sensed ocean color to characterize the ultraviolet (UV) radiation field in surface water along with quantitative chemical data for the photochemical efficiency of H2O2 formation. Wavelength- and temperature-dependent efficiency (i.e., apparent quantum yield, AQY) spectra previously reported for a variety of seawater sources, including coastal and oligotrophic stations in Antarctica, the Pacific Ocean at Station ALOHA, the Gulf of Mexico, and several sites along the eastern coast of the United States were compiled to obtain a “marine-average” AQY spectrum. To evaluate our predictions of H2O2 photoproduction in surface waters using this single AQY spectrum, we compared modeled rates to new measured rates from Gulf Stream, coastal, and nearshore river-outflow stations in the South Atlantic Bight, GA, United States; obtaining comparative differences of 33% or less. In our global model, the “marine-average” AQY spectrum was used with modeled solar irradiance, together with satellite-derived surface seawater temperature and UV optical properties, including diffuse attenuation coefficients and dissolved organic matter absorption coefficients estimated with remote sensing-based algorithms. The final product of the model, a monthly climatology of depth-resolved H2O2 photoproduction rates in the surface mixed layer, is reported for the first time and provides an integrated global estimate of ∼21.1 Tmol yr−1 for photochemical H2O2 production. This work has important implications for photo-redox reactions in seawater and improves our understanding of the role of solar irradiation on ROS cycling and the overall oxidation state in the oceans.
Intersection of stem cell biology and engineering towards next generation in vitro models of human fibrosis

Human fibrotic diseases constitute a major health problem worldwide. Fibrosis involves significant etiological heterogeneity and encompasses a wide spectrum of diseases affecting various organs. To date, many fibrosis targeted therapeutic agents failed due to inadequate efficacy and poor prognosis. In order to dissect disease mechanisms and develop therapeutic solutions for fibrosis patients, in vitro disease models have gone a long way in terms of platform development. The introduction of engineered organ-on-a-chip platforms has brought a revolutionary dimension to the current fibrosis studies and discovery of anti-fibrotic therapeutics. Advances in human induced pluripotent stem cells and tissue engineering technologies are enabling significant progress in this field. Some of the most recent breakthroughs and emerging challenges are discussed, with an emphasis on engineering strategies for platform design, development, and application of machine learning on these models for anti-fibrotic drug discovery. In this review, we discuss engineered designs to model fibrosis and how biosensor and machine learning technologies combine to facilitate mechanistic studies of fibrosis and pre-clinical drug testing.
EEG channel selection based on sequential backward floating search for motor imagery classification

Brain-computer interfaces (BCIs) based on motor imagery (MI) utilizing multi-channel electroencephalogram (EEG) data are commonly used to improve motor function of people with motor disabilities. EEG channel selection can enhance MI classification accuracy by selecting informative channels, accordingly reducing redundant information. The sequential backward floating search (SBFS) approach has been considered as one of the best feature selection methods. In this paper, SBFS is first implemented to select the optimal EEG channels in MI-BCI. Further, to reduce the time complexity of SBFS, the modified SBFS is proposed and applied to left and right hand MI tasks. In the modified SBFS, based on the map of EEG channels at the scalp, the symmetrical channels are selected as channel pairs and acceleration is thus realized by removing or adding multiple channels in each iteration. Extensive experiments were conducted on four public BCI datasets. Experimental results show that the SBFS achieves significantly higher classification accuracy (p < 0.001) than using all channels and conventional MI channels (i.e., C3, C4, and Cz). Moreover, the proposed method outperforms the state-of-the-art selection methods.
Single-cell transcriptome of Nepeta tenuifolia leaves reveal differentiation trajectories in glandular trichomes

The peltate glandular trichomes (PGTs) on Nepeta tenuifolia leaves can secrete and store bioactive essential oils. ScRNA-seq is a powerful tool for uncovering heterogeneous cells and exploring the development and differentiation of specific cells. Due to leaves rich in PGTs, the young leaves were used to isolated protoplasts and successfully captured 33,254 protoplasts for sequencing purposes. After cell type annotation, all the cells were partitioned into six broad populations with 19 clusters. Cells from PGTs were identified based on the expression patterns of trichome-specific genes, monoterpene biosynthetic genes, and metabolic analysis of PGT secretions. The developmental trajectories of PGTs were delineated by pseudotime analysis. Integrative analysis of scRNA-seq data from N. tenuifolia leaves and Arabidopsis thaliana shoot revealed that PGTs were specific to N. tenuifolia. Thus, our results provide a promising basis for exploring cell development and differentiation in plants, especially glandular trichome initiation and development.
HDAC11, an emerging therapeutic target for metabolic disorders

Histone deacetylase 11 (HDAC11) is the only member of the class IV HDAC, and the latest member identified. It is highly expressed in brain, heart, kidney and some other organs, and located in mitochondria, cytoplasm and nuclei, depending on the tissue and cell types. Although studies in HDAC11 total knockout mice suggest its dispensable features for tissue development and life, it participates in diverse pathophysiological processes, such as DNA replication, tumor growth, immune regulation, oxidant stress injury and neurological function of cocaine. Recent studies have shown that HDAC11 is also critically involved in the pathogenesis of some metabolic diseases, including obesity, diabetes and complications of diabetes. In this review, we summarize the recent progress on the role and mechanism of HDAC11 in the regulation of metabolic disorders, with the focus on its regulation on adipogenesis, lipid metabolism, metabolic inflammation, glucose tolerance, immune responses and energy consumption. We also discuss the property and selectivity of HDAC11 inhibitors and their applications in a variety of in vitro and in vivo models of metabolic disorders. Given that pharmacological and genetic inhibition of HDAC11 exerts a beneficial effect on various metabolic disorders, HDAC11 may be a potential therapeutic target to treat chronic metabolic diseases.
Digital interventions to promote physical activity among inactive adults: A study protocol for a hybrid type I effectiveness-implementation randomized controlled trial

Introduction Physical inactivity is the fourth leading risk factor for global mortality, and inactive adults have a higher risk to develop lifestyle diseases. To date, there is preliminary evidence of the efficacy of fitness technologies and other digital interventions for physical activity (PA) promotion. Intervention studies are needed to test the effectiveness and implementation of innovative PA promotion strategies. Methods and analysis The ONWARDS study is a hybrid type I effectiveness-implementation randomized control trial aiming at an inactive and presumably high-risk population living in Northern Norway. One hundred and eighty participants will be assigned to 3 groups in a 1:1:1 ratio and participate for 18 months. Participants in group A will be provided an activity tracker with the personalized metric Personal Activity Intelligence (PAI). Participants in group B will be provided with both an activity tracker with the personalized metric PAI and access to online training videos (Les Mills+) to perform home-based training. Participants in group C will be provided an activity tracker with the personalized metric PAI, home-based online training and additional peer support via social media. The primary objective is to test which combination of interventions is more effective in increasing PA levels and sustaining long-term exercise adherence. Secondary objectives include: proportion of participants reaching PA recommendations; exercise adherence; physical fitness; cardiovascular risk; quality of life; perceived competence for exercise; self-efficacy; social support; usability; users' perspectives on implementation outcomes (adoption, acceptability, adherence, sustainability). The study design will allow testing the effectiveness of the interventions while gathering information on implementation in a real-world situation. Discussion This study can contribute to reduce disparities in PA levels among inactive adults by promoting PA and long-term adherence. Increased PA might, in turn, result in better prevention of lifestyle diseases. Digital interventions delivered at home can become an alternative to training facilities, making PA accessible and feasible for inactive populations and overcoming known barriers to PA. If effective, such interventions could potentially be offered through national health portals to citizens who do not meet the minimum recommendations on PA or prescribed by general practitioners or specialists. Trial registration https://clinicaltrials.gov/ct2/show/NCT04526444, Registered 23 April 2021, identifier: NCT04526444.
Managing nature-based solutions in fire-prone ecosystems: Competing management objectives in California forests evaluated at a landscape scale

California’s cap-and-trade compliance offset market incentivizes forest managers to maintain elevated carbon stocks. It provides these incentives without enforcing standardized fire mitigation practices despite many projects being located in fire prone regions. Here, we evaluated the difference between management actions in California forests that participated in the carbon offset market versus those that engaged with state programs to reduce wildfire risk via fuel reduction treatments. Using remotely sensed data from the California Forest Observatory and the Moderate Resolution Imaging Spectroradiometer, we compared the vertical forest structure and vegetation canopy trends on forest offsets with forests that are receiving fuel treatment. We found California forests managed for carbon under the Improved Forest Management (IFM) program by the California Air Resources Board had higher levels of biomass than forests managed for fire risk reduction as indicated by 2016 lidar-estimated fuel loads. In addition, IFM-participating forests did not reduce their fuel loads between 2016 and 2020, whereas lands receiving grants for fuel management did, indicating that on average, the IFM projects were not engaging in fuel reduction efforts. However, despite the differences in fuel management between IFM projects and active fuel treatments, we found that both types of management saw a declining trend in vegetation greenness between 2015 and 2021. While declining greenness is expected of active fuel treatments associated with vegetation removal, such a trend in the case of IFM indicates additional wildfire risk. Managing forests for long-term carbon storage and sequestration requires consideration of fire risk mitigation. Given the little evidence of fuel reduction in the first decade of IFM projects implementation we question whether the century-long duration of carbon stocks in these offsets is realistic. We recommend that policymakers reevaluate the incentives directed at carbon stock preservation or expansion to better encompass the growing wildfire risk in California.
Where do our preferences come from? How hard decisions shape our preferences

COPYRIGHT © 2022 Voigt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Where do our preferences come from? How hard decisions shape our preferences
Editorial: Crop pest control and pollination

COPYRIGHT © 2022 Ouyang, Li, Xie and Men. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Crop pest control and pollination
Human placental hematopoietic stem cell-derived natural killer cells (CYNK) recognize and eliminate influenza A virus-infected cells

Influenza A virus (IAV) infections are a significant recurrent threat to public health and a significant burden on global economy, highlighting the need for developing more effective therapies. Natural killer (NK) cells play a pivotal role in the control of pulmonary IAV infection, however, little is known about the therapeutic potential of adoptively transferred NK cells for viral infections. Here, we investigated the antiviral activity of CYNK, human placental hematopoietic stem cell-derived NK cells, against IAV infection in vitro. Virus infection induced the expression of NK cell activating ligands on respiratory epithelial cells, resulting in enhanced recognition by CYNK cells. Upon co-culture with IAV-infected epithelial cells, CYNK exhibited elevated degranulation and increased production of IFN-γ, TNF-α and GM-CSF in a virus dose-dependent manner. Furthermore, CYNK showed virus dose-dependent cytotoxicity against IAV-infected cells. The antiviral activity of CYNK was mediated by NKp46 and NKG2D. Together, these data demonstrate that CYNK possesses potent antiviral function against IAV and warrant clinical investigations for adoptive NK cell therapies against viral infections.