KRAS depletion suppresses ferroptosis and affects Hippo pathway in cataract.

Cataract, a painless and progressive disorder is manifested as the opacification of the lens that represents the most significant cause of blindness worldwide. The objective of this study is to unveil the function of Kirsten rat sarcoma (KRAS) and potential action mechanisms against cataract. The ferroptosis-associated differentially expressed genes (DEGs) and pivot genes were extracted through the comprehensive bioinformatics methods. Erastin was applied for inducing ferroptosis in hydrogen peroxide (H2O2)-treated SRA01/04 cells, and validated by detecting content of intracellular iron, glutathione (GSH), malondialdehyde (MDA). Additionally, the effects of KRAS deficiency on ferroptosis were determined by functional assays. The proteins expression related to ferroptosis and Hippo pathway were determined by Western blotting. A total of 73 ferroptosis-related DEGs were discovered, and 6 critical core genes were confirmed upregulation in cataract cell model. The H2O2-treated SRA01/04 cells exhibited decrease of cell viability and proliferation, iron accumulation, MDA increase, GSH consumption, rise of COX2 and decline of GPX4, with further aggravated under erastin treatment, while the phenomena were improved by KRAS knockdown. Additionally, KRAS deficiency was involved in the Hippo signalling pathway activation. Downregulation of KRAS might restrain ferroptosis and affect Hippo pathway in cataract.

Immune cells use active tugging forces to distinguish affinity and accelerate evolution.

Cells are known to exert forces to sense their physical surroundings for guidance of motion and fate decisions. Here, we propose that cells might do mechanical work to drive their own evolution, taking inspiration from the adaptive immune system. Growing evidence indicates that immune B cells-capable of rapid Darwinian evolution-use cytoskeletal forces to actively extract antigens from other cells' surfaces. To elucidate the evolutionary significance of force usage, we develop a theory of tug-of-war antigen extraction that maps receptor binding characteristics to clonal reproductive fitness, revealing physical determinants of selection strength. This framework unifies mechanosensing and affinity-discrimination capabilities of evolving cells: Pulling against stiff antigen tethers enhances discrimination stringency at the expense of absolute extraction. As a consequence, active force usage can accelerate adaptation but may also cause extinction of cell populations, resulting in an optimal range of pulling strength that matches molecular rupture forces observed in cells. Our work suggests that nonequilibrium, physical extraction of environmental signals can make biological systems more evolvable at a moderate energy cost.

The neural habituation to hedonic and eudaimonic rewards: Evidence from reward positivity.

Rewards play an important role in people's well-being. However, the mechanisms underlying neural habituation to hedonic rewards (attainment of pleasure) and eudaimonic rewards (attainment of meaning and self-realization) and their implications for longitudinal changes in well-being remain unknown. By operationalizing hedonic rewards as "winning money for oneself" and eudaimonic rewards as "winning money for a charity", 78 participants (41 women, aged from 17 to 24 years) completed a revised monetary gambling task during event-related potential (ERP) recording. Subsequently, the participants' well-being was measured after one year. The results showed that the reward positivity (RewP) effect readily decreased as the hedonic rewards were repeated, whereas the RewP effect in response to eudaimonic rewards was relatively sustained over time. Moreover, the declining RewP effect for repeated eudaimonic rewards was marginally positively associated with longitudinal decreases in well-being. These findings demonstrate at the neural level that sensitivity to repeated hedonic rewards is more prone to decrease than sensitivity to repeated eudaimonic rewards, and sustained eudaimonic reward sensitivity in the short term has greater implications for changes in well-being in the long term.

Skin Lesion Segmentation with C-UNet.

Malignant melanoma is one of the leading cancers around the world. It is critical to timely diagnose and treat melanoma to improve patient survival. This paper proposes a deep learning model C-UNet for skin lesion segmentation. The C-UNet incorporates the Inception-like convolutional block, the recurrent convolutional block and dilated convolutional layers. We also apply a finetune technique using Dice loss after training the model with commonly used cross-entropy loss. The conditional random field was used to further smooth predicted label maps. Experiment results show that the proposed method achieves better accuracy and more robust segmentation results than UNet.

From Deep Learning Towards Finding Skin Lesion Biomarkers.

Melanoma is a type of skin cancer with the most rapidly increasing incidence. Early detection of melanoma using dermoscopy images significantly increases patients' survival rate. However, accurately classifying skin lesions by eye, especially in the early stage of melanoma, is extremely challenging for the dermatologists. Hence, the discovery of reliable biomarkers will be meaningful for melanoma diagnosis. In recent years, the value of deep learning empowered computer-assisted diagnose has been shown in biomedical imaging-based decision making. However, much deep learning research focuses on improving disease detection accuracy but not understanding the features deep learning use to determine the evidence of pathology. We aim to make sure the features used by deep learning methods are the reasonable clinical features for skin lesions diagnosis, rather than artifacts. Further, we aim to discover new biomarkers, which may not have been included in clinical criteria but do make sense to the dermatologists. Our proposed pipeline can find biomarkers for identifying different lesions. The patterns are agreed with dermatologists. Surprisingly, we find surround skins also can be used as evidence for skin lesion diagnosis, which has not been included in traditional diagnosis rules. The biomarkers discovered from deep learning classifier can be significant and useful to guide clinical diagnosis.

Temporal dynamics of hedonic and eudaimonic reward processing: An event-related potentials (ERPs) study.

Reward or pleasure can be achieved from a hedonic approach (pleasure attainment) or eudaimonic approach (meaning and self-realization). However, the neurodynamics of hedonic and eudaimonic reward processing remain unclear. By operationalizing hedonic reward as "win money for oneself" and eudaimonic reward as "win money for charity", the current study used the monetary incentive delay task to parse hedonic and eudaimonic reward dynamics into the anticipatory and consummatory stages while event-related potentials (ERPs) were recorded. 24 participants (12 women) were recruited in this study. The results showed that in the anticipatory stage, the amplitudes evoked by hedonic and eudaimonic reward did not differ during early cue recognition (P2, N2), but they separated during late cue elaboration (cue-P3). In the consummatory stage, hedonic reward elicited a larger FRN effect, but eudaimonic reward elicited a larger fb-P3 effect. In addition, we also used the neural indices of hedonic and eudaimonic reward processing to predict participants' longitudinal changes in well-being (depression and positive emotion) across 6 months as exploratory in nature. Preliminary regression evidence suggested that greater differential amplitude of cue-P3 elicited by eudaimonic reward anticipation versus neutral anticipation positively predicted longitudinal increases in positive emotion. The findings elucidated specific substages of hedonic and eudaimonic reward processing and explored their potential roles in longitudinal changes in well-being.

Active Tuning of Synaptic Patterns Enhances Immune Discrimination.

Immune cells learn about their antigenic targets using tactile sense: a self-organized motif named immunological synapse forms between an immune cell and an antigen-presenting cell (APC) during recognition. Via synapses, immune cells apply mechanical pulling forces to selectively extract antigen (Ag) from APCs. Curiously, depending on its stage of development, a B lymphocyte exhibits distinct synaptic patterns and uses force at different strength and timing, which appears to strongly impact its ability to distinguish Ag affinities. We use a statistical-mechanical model to study how the experimentally observed synaptic architectures can originate from normal cytoskeletal forces coupled to the lateral organization of mobile receptors, and show how this active regulation scheme, collective in nature, may enhance the efficiency and capacity of discrimination.

Laminins in an in vitro anterior lens capsule model established using HLE B-3 cells.

Cataracts are the most common eye disease to cause blindness in patients. The abnormal deposition of laminins (LMs) in the lens capsule and the disruption of capsular epithelium contribute to cataract development, although the mechanism by which this occurs is currently unclear. The present study aimed to reproduce HLE B­3 basement membranes (BMs) using HLE B­3 cells and to analyze the similarities of LM expression between HLE B­3 BMs and human anterior lens capsule (ALC). Immunohistochemistry (IHC), ELISA, western blot analysis and immunoprecipitation (IP)­western blot analysis were used to detect total LMs, LM trimers and 11 LM subunits in HLE B­3 cells, HLE B­3 BMs and human ALCs. In IHC staining, HLE B­3 cells and human ALCs were positive for LMs. In LM ELISA, all samples analyzed were positive for LMs. Western blot analysis detected all LM subunits except for LMγ3 in HLE B­3 cell lysate, 4 subunits (LMα4, LMα2, LMα1 and LMγ1) in HLE B­3 cell culture supernatant, 5 subunits (LMα4, LMα2, LMα1, LMß3 and LMγ1) in HLE B­3 BMs, and 3 subunits (LMα4, LMγ2 and LMγ1) in human ALCs. The results of IP­western blot analysis revealed that the LM411 trimer was detected in HLE B­3 cell culture supernatant. These results indicated that HLE B­3 BMs were similar to human ALCs in terms of LM expression. Therefore, HLE B­3 BMs could be used as an in vitro ALC model to determine the role of LMs in ALC in the pathogenesis of cataracts and to select potential anti­cataract drugs.

The complete mitochondrial genome of Gomphocerus tibetanus Uvarov, 1935 (Orthoptera: Acrididae: Gomphocerinae).

The complete nucleotide sequence of the mitochondrial genome (mitogenome) of Gomphocerus tibetanus Uvarov, 1935 (Orthoptera: Acrididae: Gomphocerinae) was determined. It is 15,571 bp in length and contains 74.8% A+T. All Gomphocerus tibetanus protein-coding sequences start with a typical ATN codon. The usual termination codons (TAA and TAG) were found from 13 PCGs except COI and COII which took incomplete codon T as termination codons. All tRNA genes could be folded into the typical cloverleaf secondary structure, except tRNA(Ser(AGN)) lacking of dihydrouridine (D) arm. The sizes of the large and small ribosomal RNA genes are 1313 and 822bp, respectively. The A+T content of the A+T-rich region is 82.3%. A preliminary analysis on characteristics of Gomphocerinae mitogenome was made by comparision among three Gomphocerinae mitogenomes and Locusta migratoria.