Urocortin 3 marks mature human primary and embryonic stem cell-derived pancreatic alpha and beta cells.

The peptide hormone Urocortin 3 (Ucn 3) is abundantly and exclusively expressed in mouse pancreatic beta cells where it regulates insulin secretion. Here we demonstrate that Ucn 3 first appears at embryonic day (E) 17.5 and, from approximately postnatal day (p) 7 and onwards throughout adult life, becomes a unifying and exclusive feature of mouse beta cells. These observations identify Ucn 3 as a potential beta cell maturation marker. To determine whether Ucn 3 is similarly restricted to beta cells in humans, we conducted comprehensive immunohistochemistry and gene expression experiments on macaque and human pancreas and sorted primary human islet cells. This revealed that Ucn 3 is not restricted to the beta cell lineage in primates, but is also expressed in alpha cells. To substantiate these findings, we analyzed human embryonic stem cell (hESC)-derived pancreatic endoderm that differentiates into mature endocrine cells upon engraftment in mice. Ucn 3 expression in hESC-derived grafts increased robustly upon differentiation into mature endocrine cells and localized to both alpha and beta cells. Collectively, these observations confirm that Ucn 3 is expressed in adult beta cells in both mouse and human and appears late in beta cell differentiation. Expression of Pdx1, Nkx6.1 and PC1/3 in hESC-derived Ucn 3(+) beta cells supports this. However, the expression of Ucn 3 in primary and hESC-derived alpha cells demonstrates that human Ucn 3 is not exclusive to the beta cell lineage but is a general marker for both the alpha and beta cell lineages. Ucn 3(+) hESC-derived alpha cells do not express Nkx6.1, Pdx1 or PC1/3 in agreement with the presence of a separate population of Ucn 3(+) alpha cells. Our study highlights important species differences in Ucn 3 expression, which have implications for its utility as a marker to identify mature beta cells in (re)programming strategies

Cross-layer similarity knowledge distillation for speech enhancement

Speech enhancement (SE) algorithms based on deep neural networks (DNNs) often encounter challenges of limited hardware resources or strict latency requirements when deployed in real-world scenarios. However, a strong enhancement effect typically requires a large DNN. In this paper, a knowledge distillation framework for SE is proposed to compress the DNN model. We study the strategy of cross-layer connection paths, which fuses multi-level information from the teacher and transfers it to the student. To adapt to the SE task, we propose a frame-level similarity distillation loss. We apply this method to the deep complex convolution recurrent network (DCCRN) and make targeted adjustments. Experimental results show that the proposed method considerably improves the enhancement effect of the compressed DNN and outperforms other distillation methods

Detecting Depression from Speech through an Attentive LSTM Network

Depression endangers people's health conditions and affects the social order as a mental disorder. As an efficient diagnosis of depression, automatic depression detection has attracted lots of researcher's interest. This study presents an attention-based Long Short-Term Memory (LSTM) model for depression detection to make full use of the difference between depression and non-depression between timeframes. The proposed model uses frame-level features, which capture the temporal information of depressive speech, to replace traditional statistical features as an input of the LSTM layers. To achieve more multi-dimensional deep feature representations, the LSTM output is then passed on attention layers on both time and feature dimensions. Then, we concat the output of the attention layers and put the fused feature representation into the fully connected layer. At last, the fully connected layer's output is passed on to softmax layer. Experiments conducted on the DAIC-WOZ database demonstrate that the proposed attentive LSTM model achieves an average accuracy rate of 90.2% and outperforms the traditional LSTM network and LSTM with local attention by 0.7% and 2.3%, respectively, which indicates its feasibility

Lipopolysaccharide-induced depression-like model in mice: meta-analysis and systematic evaluation

Depression is a complex and biologically heterogeneous disorder. Recent studies have shown that central nervous system (CNS) inflammation plays a key role in the development of depression. Lipopolysaccharide (LPS)-induced depression-like model in mice is commonly used to studying the mechanisms of inflammation-associated depression and the therapeutic effects of drugs. Numerous LPS-induced depression-like models in mice exist and differ widely in animal characteristics and methodological parameters. Here, we systematically reviewed studies on PubMed from January 2017 to July 2022 and performed cardinal of 170 studies and meta-analyses of 61 studies to support finding suitable animal models for future experimental studies on inflammation-associated depression. Mouse strains, LPS administration, and behavioral outcomes of these models have been assessed. In the meta-analysis, forced swimming test (FST) was used to evaluate the effect size of different mouse strains and LPS doses. The results revealed large effect sizes in ICR and Swiss mice, but less heterogeneity in C57BL/6 mice. For LPS intraperitoneal dose, the difference did not affect behavioral outcomes in C57BL/6 mice. However, in ICR mice, the most significant effect on behavioral outcomes was observed after the injection of 0.5 mg/kg LPS. Our results suggests that mice strains and LPS administration play a key role in the evaluation of behavioral outcomes in such models

Reactive Oxygen Species-Induced Necrotic Cell Death

Mechanisms of cell death extend beyond the simple apoptosis/necrosis relationship to include regulated modes of cell death that do not readily fit either of the classic descriptors. One such mechanism of cell death involves poly(ADP-ribose)polymerase-1 (PARP-1)-mediated cell death. 2,3,5-Tris(Glutathion-S-yl)-hydroquinone (TGHQ), a reactive oxygen species (ROS) generating nephrotoxic and nephrocarcinogenic metabolite of hydroquinone, causes necrotic renal cell death, the basis for which is unclear. We therefore investigated TGHQ-mediated cell death in human renal proximal tubule epithelial HK-2 cells. TGHQ induced ROS generation, DNA strand breaks, hyperactivation of PARP-1, rapid depletion of nicotinamide adenine dinucleotide (NAD), elevations in intracellular Ca2+ concentrations, loss of mitochondrial membrane potential, and subsequent necrotic cell death. Interestingly, PARP-1 hyperactivation was not accompanied by the translocation of apoptosis-inducing factor (AIF) from mitochondria to the nucleus, a process usually associated with PARP-dependent cell death. Inhibition of PARP-1 with PJ34 blocked TGHQ-mediated accumulation of poly(ADP-ribose) polymers, NAD consumption, and the consequent necrotic cell death. However, HK-2 cell death was only delayed by PJ34, and cell death remained necrotic in nature. In contrast, chelation of intracellular Ca2+ with BAPTA-AM completely abrogated TGHQ-induced necrotic cell death. Ca2+ chelation not only prevented the collapse in the mitochondrial potential but also attenuated PARP-1 hyperactivation. Conversely, inhibition of PARP-1 modulated TGHQ-mediated changes in Ca2+ homeostasis. Moreover, TGHQ caused a sequential oxidation of peroxiredoxin III (PrxIII), a protein considered the primary antioxidant defense within mitochondria. Thus, TGHQ induced two acidic shifts in PrxIII, with both pI shifted spots representing oxidized forms of PrxIII. Transient expression of a dominant negative version of PrxIII resulted in a significant increase in TGHQ-induced cytotoxicity, whereas overexpression of wild-type PrxIII significantly attenuated cytotoxicity. Our studies provide new insights into PARP-1-mediated necrotic cell death. Changes in intracellular Ca2+ concentrations appear to couple PARP-1-hyperactivation to subsequent cell death, but in the absence of AIF release from mitochondria. NAD depletion, mitochondrial membrane depolarization, Ca2+-mediated calpain activation, and PrxIII oxidation, all contribute to TGHQ-driven ROS-mediated necrotic cell death

Decoding the role of TET family dioxygenases in lineage specification

Abstract Since the discovery of methylcytosine oxidase ten-eleven translocation (TET) proteins, we have witnessed an exponential increase in studies examining their roles in epigenetic regulation. TET family proteins catalyze the sequential oxidation of 5-methylcytosine (5mC) to oxidized methylcytosines including 5-hydroxymethylcytosine (5hmC), 5-formylcytosine, and 5-carboxylcytosine. TETs contribute to the regulation of lineage-specific gene expression via modulating DNA 5mC/5hmC balances at the proximal and distal regulatory elements of cell identity genes, and therefore enhance chromatin accessibility and gene transcription. Emerging evidence suggests that TET dioxygenases participate in the establishment and/or maintenance of hypomethylated bivalent domains at multiple differentiation-associated genes, and thus ensure developmental plasticity. Here, we review the current state of knowledge concerning TET family proteins, DNA hydroxymethylation, their distribution, and function in endoderm, mesoderm, and neuroectoderm specification. We will summarize the evidence pertaining to their crucial regulatory roles in lineage commitment and development

Self-Fitting Algorithm for Digital Hearing Aid Based on Interactive Evolutionary Computation and Expert System

The traditional hearing aid fitting method, which mainly relies on the audiologist, is timeconsuming and messy. To improve this situation, a self-fitting algorithm based on an improved interactive evolutionary computation (IEC) algorithm and expert system, which enables the patients to fit the hearing aid by themselves, is proposed. The algorithm takes the band gain as the fitting target and uses the patient’s subjective evaluation to iteratively update the algorithm parameters based on the improved IEC algorithm. In addition, a real-time updated expert system is constructed to assist in the optimization of the initial and iterative parameters of the fitting based on the patient’s audiogram and personal information. To verify the performance of the algorithm, a self-fitting software for the hearing aid is designed. Through this software, the test signal is generated for the patient to evaluate the audio quality on a five-level scale. Based on the evaluation results, the algorithm iteratively optimizes the algorithm parameters until the patient is satisfied with the generated audio. Compared with the fitting algorithm based on Gaussian processes algorithm or the interactive evolutionary algorithm, the average subjective speech recognition rate of the proposed algorithm increase at least 11%. The average recognition rate for environmental sound is also improved by at least 2.9%. In addition, the fitting time of the proposed algorithm is shortened by at least 10 min compared to others two algorithms

A Torsion-Bending Antagonistic Bistable Actuator Enables Untethered Crawling and Swimming of Miniature Robots

Miniature robots show great potential in exploring narrow and confined spaces to perform various tasks, but many applications are limited by the dependence of these robots on electrical or pneumatic tethers to power supplies outboard. Developing an onboard actuator that is small in size and powerful enough to carry all the components onboard is a major challenge to eliminate the need for a tether. Bistability can trigger a dramatic energy release during switching between the 2 stable states, thus providing a promising way to overcome the intrinsic limitation of insufficient power of small actuators. In this work, the antagonistic action between torsional deflection and bending deflection in a lamina emergent torsional joint is utilized to achieve bistability, yielding a buckling-free bistable design. The unique configuration of this bistable design enables integrating of a single bending electroactive artificial muscle in the structure to form a compact, self-switching bistable actuator. A low-voltage ionic polymer–metal composites artificial muscle is employed, yielding a bistable actuator capable of generating an instantaneous angular velocity exceeding 300 °/s by a 3.75-V voltage. Two untethered robotic demonstrations using the bistable actuator are presented, including a crawling robot (gross weight of 2.7 g, including actuator, battery, and on-board circuit) that can generate a maximum instantaneous velocity of 40 mm/s and a swimming robot equipped with a pair of origami-inspired paddles that swims breaststroke. The low-voltage bistable actuator shows potential for achieving autonomous motion of various fully untethered miniature robots