Opposing Regulation of PROX1 by Interleukin-3 Receptor and NOTCH Directs Differential Host Cell Fate Reprogramming by Kaposi Sarcoma Herpes Virus

Lymphatic endothelial cells (LECs) are differentiated from blood vascular endothelial cells (BECs) during embryogenesis and this physiological cell fate specification is controlled by PROX1, the master regulator for lymphatic development. When Kaposi sarcoma herpes virus (KSHV) infects host cells, it activates the otherwise silenced embryonic endothelial differentiation program and reprograms their cell fates. Interestingly, previous studies demonstrated that KSHV drives BECs to acquire a partial lymphatic phenotype by upregulating PROX1 (forward reprogramming), but stimulates LECs to regain some BEC-signature genes by downregulating PROX1 (reverse reprogramming). Despite the significance of this KSHV-induced bidirectional cell fate reprogramming in KS pathogenesis, its underlying molecular mechanism remains undefined. Here, we report that IL3 receptor alpha (IL3Rα) and NOTCH play integral roles in the host cell type-specific regulation of PROX1 by KSHV. In BECs, KSHV upregulates IL3Rα and phosphorylates STAT5, which binds and activates the PROX1 promoter. In LECs, however, PROX1 was rather downregulated by KSHV-induced NOTCH signal via HEY1, which binds and represses the PROX1 promoter. Moreover, PROX1 was found to be required to maintain HEY1 expression in LECs, establishing a reciprocal regulation between PROX1 and HEY1. Upon co-activation of IL3Rα and NOTCH, PROX1 was upregulated in BECs, but downregulated in LECs. Together, our study provides the molecular mechanism underlying the cell type-specific endothelial fate reprogramming by KSHV

Kaposin-B Enhances the PROX1 mRNA Stability during Lymphatic Reprogramming of Vascular Endothelial Cells by Kaposi's Sarcoma Herpes Virus

Kaposi's sarcoma (KS) is the most common cancer among HIV-positive patients. Histogenetic origin of KS has long been elusive due to a mixed expression of both blood and lymphatic endothelial markers in KS tumor cells. However, we and others discovered that Kaposi's sarcoma herpes virus (KSHV) induces lymphatic reprogramming of blood vascular endothelial cells by upregulating PROX1, which functions as the master regulator for lymphatic endothelial differentiation. Here, we demonstrate that the KSHV latent gene kaposin-B enhances the PROX1 mRNA stability and plays an important role in KSHV-mediated PROX1 upregulation. We found that PROX1 mRNA contains a canonical AU-rich element (ARE) in its 3′-untranslated region that promotes PROX1 mRNA turnover and that kaposin-B stimulates cytoplasmic accumulation of the ARE-binding protein HuR through activation of the p38/MK2 pathway. Moreover, HuR binds to and stabilizes PROX1 mRNA through its ARE and is necessary for KSHV-mediated PROX1 mRNA stabilization. Together, our study demonstrates that kaposin-B plays a key role in PROX1 upregulation during lymphatic reprogramming of blood vascular endothelial cells by KSHV

Nonlinear Distortion Mitigation in Multi-IF over Fiber Transmission Using Modulation-Based Adaptive Power Allocation

We propose a modulation-based adaptive power allocation (MBAPA) technique for nonlinear distortion mitigation in intermediate frequency over fiber (IFoF) systems. The technique allocates the spectral power of each IF band according to the required signal-to-noise power ratio (SNR) of the modulation format. To demonstrate the performance of the technique, transmission experiments were performed in 10 km and 20 km with 24-IF bands using OFDM signals. The feasibility of the proposed MBAPA technique was experimentally verified by reducing inter-modulation distortion (IMD) power and enhancing channel linearity

Teleworking Is Significantly Associated with Anxiety Symptoms and Sleep Disturbances among Paid Workers in the COVID-19 Era

Due to social distancing during COVID-19, teleworking has spread in Korea. Accordingly, the effects of teleworking on physical and mental health have emerged. We aim to determine the association between teleworking and mental health, including anxiety symptoms and sleep disturbance, in paid workers. The data of paid workers from the Sixth Korean Working Conditions Survey, collected between October 2020 and April 2021, were analyzed. Gender stratification analysis and propensity score matching were performed for variables relevant to sociodemographic and occupational characteristics. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for each sex were analyzed using multivariable logistic regression, adjusting for sociodemographic and occupational characteristics. Among 28,633 participants, analyses were performed for anxiety symptoms (teleworkers vs. non-teleworkers; men: 12.1% vs. 4.9%; women: 13.5% vs. 5.3%) and sleep disturbance (men: 33.6% vs. 21.3%; women: 39.7% vs. 25.3%). In male teleworkers, the AORs for anxiety symptoms and sleep disturbance were 1.86 (95% CI: 1.14–3.04) and 1.52 (95% CI: 1.10–2.11), respectively. In female teleworkers, the AORs for anxiety symptoms and sleep disturbance were 1.66 (95% CI: 1.13–2.43) and 1.65 (95% CI: 1.28–2.14), respectively. Our results emphasize the importance of mental health and the need for continuous education and care for teleworkers, given the rapid increase in teleworking

High heat storing and thermally diffusive artificial skin for wearable thermal management

Thermal management for wearable devices is of great importance since heat generation from electronic devices can cause adverse effects such as skin burns and malfunctioning of the devices. Here, we present an advanced thermal skin (ATS) based on a hybrid structure that exhibits both high thermal diffusivity and thermal storage capability. Silver flake/polydimethylsiloxane (PDMS) serpentine structure (SPS) and sodium-acetate-based hydrogel matrix (SAHM) form an interfacial layer between the skin and wearable device not only to ther-mally protect the skin but also to prevent the device from malfunctioning by absorbing the heat released from the device. The high thermal diffusivity of SPS serves to spread the heat, while the high thermal storage capability of SAHM facilitates heat absorption without a significant temperature increase. Unlike the general phase change materials (PCMs), SAHM retains a small modulus change of 4.8 fold while maintaining comparable heat capacity to paraffin. Such a skin-like softness of ATS regardless of its phase has not yet been reported elsewhere to the authors' best knowledge. This property enables conformal contact with the deformable surface and increases its applicability to wearable thermal management, and in this regard, we expect that this study will make significant contributions to the heat management of future wearables.N

3D cell-printing of tendon-bone interface using tissue-derived extracellular matrix bioinks for chronic rotator cuff repair

The tendon-bone interface (TBI) in rotator cuffs exhibits a structural and compositional gradient integrated through the fibrocartilaginous transition. Owing to restricted healing capacity, functional regeneration of the TBI is considered a great clinical challenge. Here, we establish a novel therapeutic platform based on 3D cell-printing and tissue-specific bioinks to achieve spatially-graded physiology for functional TBI regeneration. The 3D cell-printed TBI patch constructs are created via a spatial arrangement of cell-laden tendon and bone-specific bioinks in a graded manner, approximating a multi-tissue fibrocartilaginous interface. This TBI patch offers a cell favorable microenvironment, including high cell viability, proliferative capacity, and zonal-specific differentiation of encapsulated stem cells for TBI formation in vitro. Furthermore, in vivo application of spatially-graded TBI patches with stem cells demonstrates their regenerative potential, indicating that repair with 3D cell-printed TBI patch significantly accelerates and promotes TBI healing in a rat chronic tear model. Therefore, our findings propose a new therapeutic strategy for functional TBI regeneration using 3D cell-printing and tissue-specific decellularized extracellular matrix bioink-based approach.11Nsciescopu

Lithium metal anode on a copper dendritic superstructure

Li-metal is one of the most promising anode materials for electrochemical energy storage. However, the growth of Li dendrites during electrochemical deposition leads to low Coulombic efficiency and safety concerns and has long hindered the application of rechargeable Li-metal batteries. In this study, we designed a Cu dendritic superstructure with macropores as an anode-free three-dimensional current collector, which can significantly improve the electrochemical plating/stripping behavior of Li. The Li-metal anodes are accommodated by a Cu dendritic superstructure with no uncontrollable Li dendrites. This anode can operate for more than 600 h without a short-circuit and exhibits a low level of voltage hysteresis (~20 mV). The anode-free dendritic superstructure demonstrates exceptional performance and highlights the importance of rational design for a current collector that can accommodate Li anodes and provide a long lifespan. Keywords: Li-metal batteries, Anode-free batteries, Hierarchical current collector, Three-dimensional cu current collecto

Valproic Acid-Induced CCN1 Promotes Osteogenic Differentiation by Increasing CCN1 Protein Stability through HDAC1 Inhibition in Tonsil-Derived Mesenchymal Stem Cells

Our previous study found that the level of CCN1 increases as osteogenic differentiation progresses in tonsil-derived mesenchymal stem cells (TMSCs). This study investigated how CCN1 is regulated through HDAC inhibition in TMSCs and their relationship with osteogenesis. Valproic acid (VPA) (1–5 mM), a well-known histone deacetylase (HDAC) inhibitor, strongly inhibited TMSC proliferation without altering MSC-specific surface markers, CD14, 34, 45, 73, 90 and 105. However, CD146 expression increased at 5 mM VPA. VPA increased osteogenic differentiation of TMSCs but decreased adipogenesis and chondrogenesis, as evidenced by the cell-specific staining of differentiation. The former was validated by the increased osteocalcin (OCN). The changes in CCN1 by VPA was biphasic; it increased until 48 h and decreased thereafter. Knockdown of CCN1 by using siRNA inhibited the osteogenic effect of VPA. VPA had no effect on CCN1 mRNA expression, but inhibition of protein synthesis by cycloheximide showed that VPA slowed down the CCN1 protein degradation. Moreover, overexpression of HDAC1 completely inhibited VPA-induced CCN1. Our results indicate that VPA inhibits the HDAC1, inducing CCN1 protein stability rather than gene expression, thereby promoting osteogenic differentiation of TMSCs. These findings present the noble implication of VPA as an inhibitor of HDAC1 to facilitate CCN1-induced osteogenic differentiation of MSCs

Bioinspired untethered soft robot with pumpless phase change soft actuators by bidirectional thermoelectrics

© 2022 Elsevier B.V.Soft pneumatic actuators play an important role in the technological advancement of soft robotics, but they face intrinsic limitations due to the presence of complex and bulky air compressors and tubes, that make it difficult to design completely soft robotic systems. In this study, we develop a first demonstration of the soft thermo-pneumatic actuating module that operates based on the thermally controlled gas-liquid phase transition with the soft thermoelectric device. The bi-directional thermal managing ability (heating and cooling) of the thermoelectric device is capable of controlling the inflation and deflation of the pneumatic chamber with the aid of the thermally conductive silicone rubber that enhances the heat transfer. For the first time to the authors best knowledge, we demonstrate the active cooling of the thermoelectric device that accelerates the deflation rate by the active cooling functionality that significantly reduces the whole operating time. Additionally, to validate its practical usage in soft robotics, the soft actuating module shows different motions, such as bending and rectilinear stretching, based on the assembly design that is employed to develop the soft gripper and the entirely untethered soft earthworm robot without a complicated and bulky compressor system.N