Miracle-dz/UniFAR-FTUs huggingface dataset:
Mortalin (HSPA9) facilitates BRAF-mutant tumor cell survival by suppressing ANT3-mediated mitochondrial membrane permeability

Blocking the heat shock chaperone mortalin kills BRAF-mutant and MEK-ERK pathway–driven tumor cells. Mortalin blocks oncogenic cell death Oncogenic stress can kill cells, yet oncogenic mutations in the kinase BRAF result in enhanced cell survival, often despite the use of targeted inhibitors. Wu et al. found that a heat shock protein (HSP70)–related chaperone protein called mortalin was critical to blocking a cell death mechanism in BRAF-mutant cells. They found that aberrant activity of the MEK-ERK signaling cascade caused by BRAF mutation or RAF-derived fusion protein promoted a protein-protein interaction that, in the absence of mortalin, induced mitochondrial-mediated cell death. Depleting mortalin or treating cells with HSP70 inhibitor derivatives was cytotoxic selectively to BRAF-mutant cells, including those resistant to the BRAF inhibitor vemurafenib, suggesting that blocking mortalin might be therapeutically effective in BRAF-MEK-ERK pathway–driven tumors. Mortalin [also known as heat shock protein family A (HSP70) member 9 (HSPA9) or glucose-regulated protein 75 (GRP75)] is a mitochondrial molecular chaperone that is often up-regulated and mislocalized in tumors with abnormal activation of the kinases MEK and ERK. Here, we found that mortalin depletion was selectively lethal to tumor and immortalized normal cells expressing the mutant kinase B-RafV600E or the chimeric protein ΔRaf-1:ER and that MEK-ERK–sensitive regulation of the peptide-binding domain in mortalin was critical to cell survival or death. Proteomics screening identified adenine nucleotide translocase 3 (ANT3) as a previously unknown mortalin substrate and cell survival/death effector. Mechanistically, increased MEK-ERK signaling activity and mortalin function converged opposingly on the regulation of mitochondrial permeability. Specifically, whereas MEK-ERK activity increased mitochondrial permeability by promoting the interaction between ANT3 and the peptidyl-prolyl isomerase cyclophilin D (CypD), mortalin decreased mitochondrial permeability by inhibiting this interaction. Hence, mortalin depletion increased mitochondrial permeability in MEK-ERK–deregulated cells to an extent that triggered cell death. HSP70 inhibitor derivatives that effectively inhibited mortalin suppressed the proliferation of B-RafV600E tumor cells in culture and in vivo, including their B-Raf inhibitor–resistant progenies. These findings suggest that targeting mortalin has potential as a selective therapeutic strategy in B-Raf–mutant or MEK-ERK–driven tumors.
Effects of a Physical Activity Intervention on Physical Fitness of schoolchildren: The Enriched Sport Activity Program

Background: Physical fitness in youth is a predictor of health in adulthood. The main objective of the present study was to understand if an enriched sport activity program could increase physical fitness in a population of schoolchildren. Methods: In a sample of 672 children aged 10.0 ± 1.90 years, different motor skills were tested by the 1 kg and 3 kg ball throw (BT), the standing broad jump (SBJ), the 30 m sprint (30mS), the leger shuttle run (LSR), the illinois agility test (IGT), and the quadruped test (QT). Within the controlled-trial, the intervention group (ESA) underwent an additional warm-up protocol, which included cognitive enhancing elements, for 14 weeks while the control group continued with ordinary exercise activity. Results: A significant increase was present regarding the 1 kg and 3 kg BT, the SBJ, the 30mS, and the IGT, while no significant difference was shown regarding the QT and the LSR in the ESA group between pre and post intervention. In the control group, no differences were present for any test except for the QT and the LSR post-test. Conclusion: A 14-week structured physical intervention had moderate effects regarding throwing, jumping, sprinting, and agility in a sample of schoolchildren.
Inverted Si:PbS Colloidal Quantum Dots Heterojunction Based Infrared Photodetector.

Silicon and PbS colloidal quantum dots heterojunction photodetector combines the advantages of Si device and PbS CQDs, presenting a promising strategy for infrared light detecting. However, the construction of high quality CQDs:Si heterojunction remains to be a challenge. In this work, we introduce an inverted structure photodetector based on n-type Si and p-type PbS CQDs. Compared with the existing normal structure photodetector with p-type Si and n-type PbS CQDs, it has lower energy band offset which provides higher efficient charge extraction for device. With the help of Si wafer surface passivation and the Si doping density optimization, the device delivers a high detectivity of 1.47×1011 Jones at 1540 nm without working bias, achieving the best performance in Si/PbS photodetectors now. This work provides a new strategy to fabricate low cost high performance PbS CQDs photodetector compatible with silicon arrays.
Biomass and carbon estimation for scrub mangrove forests and examination of their allometric associated uncertainties

Reliable estimates of biomass and carbon storage are essential for the understanding of the environmental drivers and processes that regulate the productivity of scrub forests. The present study estimated total (above-ground, AGB + below-ground, BGB) biomass and carbon storage of a scrub forest dominated by Avicennia germinans (L.) L. based on the existing allometric models for the AGB, while novel models were developed to estimate the BGB. Data collection followed a destructive approach by using the "sampling method", from 45 trees divided into three height classes. Tree height and diameter were used to estimate the BGB of these forests, providing more accurate estimates of their biomass. Our findings indicate the existence of a direct relationship with increasing topography and interstitial salinity, which result in an increase in the percentage contribution of the AGB. By contrast, increasing topography also led to reduction in tree height and contribution of the BGB, although this compartment represents approximately half of the total biomass of these forests. The contribution of BGB estimates increased from 43 to 49.5% from the lowest to the highest height class and the BGB and AGB values reached approximately 87 Mg ha-1 (48.6%) and 91.7 Mg ha-1 (51.4%), respectively. The estimates of the biomass and carbon stocks of scrub mangroves vary considerably worldwide, which reflects the uncertainties derived from the application of distinct sampling methods. Specific models developed for each height class should be considered instead generalist models to reduce the general uncertainties on the production and distribution of biomass and the storage of carbon. Overall, our results overcome a major lacuna in the development of allometric equations to estimate the production of BGB and the storage of carbon by scrub mangrove forests, contributing to the refinement of the total biomass estimates for this type of mangrove forest.
PBX1 acts as terminal selector for olfactory bulb dopaminergic neurons

ABSTRACT Neuronal specification is a protracted process that begins with the commitment of progenitor cells and culminates with the generation of mature neurons. Many transcription factors are continuously expressed during this process but it is presently unclear how these factors modify their targets as cells transition through different stages of specification. In olfactory bulb adult neurogenesis, the transcription factor PBX1 controls neurogenesis in progenitor cells and the survival of migrating neuroblasts. Here, we show that, at later differentiation stages, PBX1 also acts as a terminal selector for the dopaminergic neuron fate. PBX1 is also required for the morphological maturation of dopaminergic neurons and to repress alternative interneuron fates, findings that expand the known repertoire of terminal-selector actions. Finally, we reveal that the temporal diversification of PBX1 functions in neuronal specification is achieved, at least in part, through the dynamic regulation of alternative splicing. In Caenorhabditis elegans, PBX/CEH-20 also acts as a dopaminergic neuron terminal selector, which suggests an ancient role for PBX factors in the regulation of terminal differentiation of dopaminergic neurons. Highlighted Article: In adult neurogenesis, PBX1 acts as terminal selector for dopaminergic neuron fate in addition to its known pro-neurogenic role in progenitors. Alternative splicing is important to confer functional diversity to PBX1.
Applying CRISPR-Cas12a as Signal Amplifier to Construct Biosensors for Non-DNA Targets in Ultra-low Concentrations.

Efficient signal amplification is essential to construct ultrasensitive biosensors for biologically relevant species with abundant concomitant interferences. Here we apply LbaCas12a as signal amplifier to develop versatile CRISPR-Cas12a platform to detect a wide range of analytes in ultra-low concentrations. The platform relies on the indiscriminate single-stranded DNase activity of LbaCas12a, which recognizes ssDNA intermediates generated by non-DNA targets in down to femtomolar concentrations and subsequently enhances the fluorescence signal output. With the help of functional nucleotides (DNAzyme and aptamer), ultrasensitive bioassays for Pb2+ and Acinetobacter baumannii have been designed with a limit of detection down to ~ 0.053 nM and ~ 3 CFU/mL, respectively. It also allows simultaneous detection of four miRNAs at pM concentration without significant interferences by other counterparts, suggesting the potential of multiplexed miRNA expression profiles analysis in high-throughput. Given the versatility and generality and of the CRISPR-Cas12a platform, we expect the current work advance the application of CRISPR-Cas-based platforms in bio-analysis and provide new insights into ultrasensitive biosensor design.
Evaluation of Waste Mushroom Compost as a Feed Supplement and Its Effects on the Fat Metabolism and Antioxidant Capacity of Broilers

Simple Summary Mushroom waste compost is the main byproduct when cultivating mushrooms. Due to its high mycelium content, mushroom waste compost may improve animal health by increasing antioxidant capacity. Furthermore, increasing evidence suggests that supplementing animal diets with fiber could improve body composition and health. The results showed that supplementation with mushroom waste compost accelerates adipolysis and enhances the antioxidant capacity of broilers. Among all treatment groups, broilers given dietary supplementation with 0.5% mushroom waste compost showed improved feed conversion rate and the highest adipose metabolism. Abstract Pennisetum purpureum Schum No. 2 waste mushroom compost (PWMC) is the main byproduct when cultivating Pleurotus eryngii. Due to the high mycelium levels in PWMC, it may have potential as a feed supplement for broilers. This study investigated the effects of PWMC supplementation on antioxidant capacity and adipose metabolism in broilers. In the study, 240 broilers were randomly allocated to one of four treatment groups: basal diet (control), 0.5%, 1%, or 2% PWMC supplementation. Each treatment group had 60 broilers, divided into three replicates. The results showed that supplementation with 0.5% PWMC decreased the feed conversion rate (FCR) from 1.36 to 1.28, compared to the control. Supplementation with 0.5% or 2% PWMC decreased glucose and triglyceride levels, compared to the control (p < 0.0001), the concentrations of adiponectin and oxytocin increased from 5948 to 5709, 11820, and 7938 ng/ mL; and 259 to 447, 873, and 963 pg/ mL, respectively. Toll-like receptor 4 was slightly increased in the 0.5% and 1% PWMC groups. Both interferon-γ (IFN-γ) and interleukin-1ß (IL-1ß) were significantly decreased, by about three to five times for IFN-γ (p < 0.0001) and 1.1 to 1.6 times for IL-1ß (p = 0.0002). All antioxidant-related mRNA, including nuclear factor erythroid 2–related factor 2 (Nrf-2) and superoxidase dismutase-1 (SOD-1), increased significantly following PWMC supplementation. Both claudin-1 and zonula occludens 1 increased, especially in the 2% PWMC group. Excitatory amino acid transporter 3 (EAAT3) significantly increased by about 5, 12, and 11 times in the 0.5%, 1%, and 2% PWMC groups. All adipolysis-related mRNA were induced in the PWMC treatment groups, further enhancing adipolysis. Overall, 0.5% PWMC supplementation was recommended due to its improving FCR, similar antioxidant capacity, and upregulated adipolysis.
A preliminary computational outputs versus experimental results: Application of sTRAP, a biophysical tool for the analysis of SNPs of transcription factor‐binding sites

In the human genome, the transcription factors (TFs) and transcription factor‐binding sites (TFBSs) network has a great regulatory function in the biological pathways. Such crosstalk might be affected by the single‐nucleotide polymorphisms (SNPs), which could create or disrupt a TFBS, leading to either a disease or a phenotypic defect. Many computational resources have been introduced to predict the TFs binding variations due to SNPs inside TFBSs, sTRAP being one of them.
Analysis and prospect of clinical psychology based on topic models: hot research topics and scientific trends in the latest decades

ABSTRACT The popularity of research topics in clinical psychology has always been changing over time. In this study, we use Latent Dirichlet Allocation (LDA), a well-established statistical modeling approach in machine learning, to extract hot research topics in published review articles in clinical psychology. In Study 1, we use LDA to extract existing topics between 1981 to 2018 from the review articles published on three premium journals in clinical psychology. Results provide stable information about all topics and their proportions. In Study 2, we use a dynamic variant of LDA to identify the development of hot topics from 2007 to 2018. Results show that meta-analysis, psychotherapy, professional development, and depression constantly stay as hot topics all over the 12 years. We also find that behavior intervention has a clear rising trend since 2007. Our results provide a comprehensive summary of the popularity of research topics in clinical psychology in the last couple of years, and the results here can help clinical researchers form a structured view of past research and plan future research directions.
A comparison of imaging software and conventional cell counting in determining melanocyte density in photodamaged control sample and melanoma in situ biopsies

Objective methods for distinguishing melanoma in situ (MIS) from photodamaged skin (PS) are needed to guide treatment in patients with melanocytic proliferations. Melanocyte density (MD) could serve as an objective histopathological criterion in difficult cases. Calculating MD via manual cell counts (MCC) with immunohistochemical (IHC)‐stained slides has been previously published. However, the clinical application of this method is questionable, as quantification of MD via MCC on difficult cases is time consuming, especially in high volume practices.
Development and validation of a lipogenic genes panel for diagnosis and recurrence of colorectal cancer

Background & aim Accumulated evidence indicates that the elevation of lipid metabolism is an essential step in colorectal cancer (CRC) development, and analysis of the key lipogenic mediators may lead to identifying the new clinically useful prognostic gene signatures. Methods The expression pattern of 61 lipogenic genes was assessed between CRC tumors and matched adjacent normal tissues in a training set (n = 257) with the Mann-Whitney U test. Cox's proportional hazards model and the Kaplan–Meier method were used to identifying a lipogenic-biomarkers signature associated with the prognosis of CRC. The biomarkers signature was then confirmed in two independent validation groups, including a set of 223 CRC samples and an additional set of 203 COAD profiles retrieving from the Cancer Genome Atlas (TCGA). Results Five genes, including ACOT8, ACSL5, FASN, HMGCS2, and SCD1, were significantly enhanced in CRC tumors. Using the cutoff value 0.493, the samples were classified into high risk and low risk. The AUC of panel for discriminating of all, early (I-II stages), and advanced CRC (III-IV stages) were 0.8922, 0.8446, and 0.9162 (Training set), along with 0.8800, 0.8205, and 0.7351 (validation set I), and 0.9071, 0.8946, and 0.9107 (Validation set II), respectively. There was a reverse correlation between the high predicted point of panel and worse OS of CRC patients in training set (HR (95% CI): 0.1096 (0.07089–0.1694), P < 0.001), validation set I (HR (95% CI): 0.3350 (0.2116–0.5304), P < 0.001), and validation set II (HR (95% CI): 0.1568 (0.1090–0.2257), P < 0.001). Conclusion Our study showed that the panel of ACOT8/ACSL5/FASN/HMGBCS2/SCD1 genes had a better prognostic performance than validated clinical risk scales and is applicable for early detection of CRC and tumor recurrence.
Human Vital Signs Detection Methods and Potential Using Radars: A Review

Continuous monitoring of vital signs, such as respiration and heartbeat, plays a crucial role in early detection and even prediction of conditions that may affect the wellbeing of the patient. Sensing vital signs can be categorized into: contact-based techniques and contactless based techniques. Conventional clinical methods of detecting these vital signs require the use of contact sensors, which may not be practical for long duration monitoring and less convenient for repeatable measurements. On the other hand, wireless vital signs detection using radars has the distinct advantage of not requiring the attachment of electrodes to the subject’s body and hence not constraining the movement of the person and eliminating the possibility of skin irritation. In addition, it removes the need for wires and limitation of access to patients, especially for children and the elderly. This paper presents a thorough review on the traditional methods of monitoring cardio-pulmonary rates as well as the potential of replacing these systems with radar-based techniques. The paper also highlights the challenges that radar-based vital signs monitoring methods need to overcome to gain acceptance in the healthcare field. A proof-of-concept of a radar-based vital sign detection system is presented together with promising measurement results.
Cuffless Single-Site Photoplethysmography for Blood Pressure Monitoring

One in three adults worldwide has hypertension, which is associated with significant morbidity and mortality. Consequently, there is a global demand for continuous and non-invasive blood pressure (BP) measurements that are convenient, easy to use, and more accurate than the currently available methods for detecting hypertension. This could easily be achieved through the integration of single-site photoplethysmography (PPG) readings into wearable devices, although improved reliability and an understanding of BP estimation accuracy are essential. This review paper focuses on understanding the features of PPG associated with BP and examines the development of this technology over the 2010–2019 period in terms of validation, sample size, diversity of subjects, and datasets used. Challenges and opportunities to move single-site PPG forward are also discussed.
Invasive Saltcedar and Drought Impact Ant Communities and Isopods in South-Central Nebraska

Abstract The establishment and spread of non-native species often results in negative impacts on biodiversity and ecosystem function. Several species of saltcedar, Tamarix spp. L. , have been recently naturalized in large portions of the United States where they have altered plant and animal communities.To test the prediction that saltcedar negatively affects invertebrates, we measured ant genera diversity and the activity density of the exotic isopod Armadillidium vulgare Latrielle (Isopoda: Oniscoidea) for 2 yr using pitfall traps located within 30 5-m2 plots with or without saltcedar at a south-central Nebraska reservoir. From 2005 to 2006, we collected 10,837 ants representing 17 genera and 4,953 A. vulgare. Per plot, the average number of ant genera was not different between saltcedar (x̄ = 3.9) and nonsaltcedar areas (x̄ = 3.9); however, saltcedar plots were compositionally different and more similar from plot to plot (i.e., they had lower beta diversity than control plots) in 2005, but not in 2006. Isopods were likewise temporally affected with higher activity density (+89%) in control plots in 2005, but higher activity density (+27%) in saltcedar plots in 2006.The observed temporal differences occurred as the drought that initially enabled the saltcedar invasion became less severe in 2006. Combined, our results suggest that invertebrate groups like ants, which are generally omnivorous, may be better equipped than more specialized taxa like detritivores to withstand habitat changes due to invasions by non-native species, especially during extreme weather events such as prolonged droughts.
Gut microbial diversity and stabilizing functions enhance the plateau adaptability of Tibetan wild ass (Equus kiang)

Interactions between gut microbiota not only regulate physical health, but also form a vital bridge between the environment and the host, thus helping the host to better adapt to the environment. The improvement of modern molecular sequencing techniques enables in‐depth investigations of the gut microbiota of vertebrate herbivores without harming them. By sequencing the 16S rRNA V4‐V5 region of the gut microbiota of both the captive and wild kiang in winter and summer, the diversity and function of the microbiota could be compared. The reasons for observed differences were discussed. The results showed that the dominant phyla of the kiang were Bacteroidetes and Firmicutes, and the structure and abundance of the gut microbiota differed significantly between seasons and environments. However, the relatively stable function of the gut microbiota supplies the host with increased adaptability to the environment. The diversity of the intestinal flora of the kiang is relatively low in captivity, which increases their risk to catch diseases to some extent. Therefore, importance should be attached to the impact of captivity on wildlife.
Transcranial Focused Ultrasound Modulates Electrical Behavior of the Neurons: Design and Implementation of a Model

Background: Recently, ultrasonic neuromodulation research has been an important and interesting issue. Ultrasonic neuromodulation is possible by the use of low-intensity transcranial focused ultrasound (tFUS) to stimulate or inhibit the neural structures. The primary capability of this method is the improvement in the treatment progress of certain neurological and psychiatric disorders noninvasively. tFUS is able to modulate ionic currents and neural depolarization, causing the alteration in electrical properties of neurons Objective: The study aims to investigate the effect of tFUS waves on the electrical behavior of neurons using the simulation method Material and Methods: In the first part of this simulation study, the propagation of tFUS waves throughout the head was simulated to calculate the value of acoustic pressure at the cortex. In the second part, cortical neurons were simulated by a simple model of spiking neurons proposed by Izhikevich for three common dynamics. Then, the capacitance model was proposed to determine the alteration in the electrical behavior of the neurons during tFUS stimulation. Results: At the resting state, the electric potential of the neuron’s membrane through the tFUS stimulation has an amplitude of about 30 mv with the similar oscillatory behavior of the acoustic waveform; while,the ultimate electrical behavior of the neuron’s membrane indicates a decrease in the electric potential when the neurons fire Conclusion: The electrical behavior of the neuron and the range of its membrane voltage modulated during ultrasonic stimulation. The reduction in the amplitude of membrane potential was observed while neuron spikes