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In the era of 5 G, the rise in power density in miniaturized, flexible electronic devices has created an urgent need for thin, flexible, polymer-based electrically and thermally conductive nanocomposites to address challenges related to electromagnetic interference (EMI) and heat accumulation. However, the difficulties in establishing enduring and continuous transfer pathways for electrons and phonons using solid-rigid conductive fillers within insulative polymer matrices limit the development of such nanocomposites. Herein, we incorporate MXene-bridging-liquid metal (MBLM) solid-liquid bi-continuous electrical-thermal conductive networks within aramid nanofiber/polyvinyl alcohol (AP) matrices, resulting in the AP/MBLM nanocomposite with ultra-high electrical conductivity (3984 S/cm) and distinguished thermal conductivity of 13.17 W m −1 K −1 . This nanocomposite exhibits excellent EMI shielding efficiency ( SE ) of 74.6 dB at a minimal thickness of 22 μm, and maintains high EMI shielding stability after enduring various harsh conditions. Meanwhile, the AP/MBLM nanocomposite also demonstrates promising heat dissipation behavior. This work expands the concept of creating thin films with high electrical and thermal conductivity. Composites of MXene-bridging-liquid metal (MBLM) networks in aramid nanofiber/polyvinyl alcohol matrices are developed, achieving high electrical and thermal conductivity, along with EMI shielding of 74.6 dB at 22 μm thickness

TDP-43 is a nuclear factor that functions in promoting pre-mRNA splicing. Deletion of the N-terminal domain (NTD) and nuclear localization signal (NLS) (i.e., TDP-35) results in mislocalization to cytoplasm and formation of inclusions. However, how the NTD functions in TDP-43 activity and proteinopathy remains largely unknown. Here, we studied the structure and function of the NTD in inclusion formation and pre-mRNA splicing of TDP-43 by using biochemical and biophysical approaches. We found that TDP-43 NTD forms a homodimer in solution in a concentration-dependent manner, and formation of intermolecular disulfide results in further tetramerization. Based on the NMR structure of TDP-43 NTD, the dimerization interface centered on Leu71 and Val72 around the β7-strand was defined by mutagenesis and size-exclusion chromatography. Cell experiments revealed that the N-terminal dimerization plays roles in protecting TDP-43 against formation of cytoplasmic inclusions and enhancing pre-mRNA splicing activity of TDP-43 in nucleus. This study may provide mechanistic insights into the physiological function of TDP-43 and its related proteinopathies.

While modernization has dramatically increased lifespan, it has also witnessed that the nature of stress has changed dramatically. Chronic stress result failures of homeostasis thus lead to various diseases such as atherosclerosis, non-alcoholic fatty liver disease (NAFLD) and depression. However, while 75%-90% of human diseases is related to the activation of stress system, the common pathways between stress exposure and pathophysiological processes underlying disease is still debatable. Chronic inflammation is an essential component of chronic diseases. Additionally, accumulating evidence suggested that excessive inflammation plays critical roles in the pathophysiology of the stress-related diseases, yet the basis for this connection is not fully understood. Here we discuss the role of inflammation in stress-induced diseases and suggest a common pathway for stress-related diseases that is based on chronic mild inflammation. This framework highlights the fundamental impact of inflammation mechanisms and provides a new perspective on the prevention and treatment of stress-related diseases.

Pathological aggregation of a specific protein into insoluble aggregates is a common hallmark of various neurodegenerative diseases (NDDs). In the earlier literature, each NDD is characterized by the aggregation of one or two pathogenic proteins, which can serve as disease-specific biomarkers. The aggregation of these specific proteins is thought to be a major cause of or deleterious result in most NDDs. However, accumulating evidence shows that a pathogenic protein can interact and co-aggregate with other pathogenic proteins in different NDDs, thereby contributing to disease onset and progression synergistically. During the past years, more than one type of NDD has been found to co-exist in some individuals, which may increase the complexity and pathogenicity of these diseases. This article reviews and discusses the biochemical characteristics and molecular mechanisms underlying the co-aggregation and co-pathologies associated with TDP-43 pathology. The TDP-43 aggregates, as a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), can often be detected in other NDDs, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and spinocerebellar ataxia type 2 (SCA2). In many cases, TDP-43 is shown to interact and co-aggregate with multiple pathogenic proteins in vitro and in vivo. Furthermore, the co-occurrence and co-aggregation of TDP-43 with other pathogenic proteins have important consequences that may aggravate the diseases. Thus, the current viewpoint that the co-aggregation of TDP-43 with other pathogenic proteins in NDDs and their relevance to disease progression may gain insights into the patho-mechanisms and therapeutic potential of various NDDs.

Insects are captured by the carnivorous plant Nepenthes alata when they ‘aquaplane’ on the wet rim, or ‘peristome’, of the plant’s pitcher organ; here it is shown that unidirectional water flow is crucial to the complete wetting of the peristome, and that the underlying mechanism involves multiscale structural features. Pitcher plants have a way with water The carnivorous plant Nepenthes alata captures insects when they 'aquaplane' on the wet rim, or peristome, of the plant's pitcher organ. Huawei Chen and colleagues show that this is achieved through continuous directional water transport on the peristome surface, a result of multi-scale structure features involving periodic duck-billed micro-cavities with arch-shaped open edges. These features optimize capillary rise in the transport direction and prevent back-flow by pinning in place any water front moving in the reverse direction. This produces unidirectional flow despite the absence of any gradient in surface energy, and much faster transport than previously observed with asymmetrically structured surfaces. The mechanisms underlying this behaviour could be relevant for artificial fluid-transport systems with practical applications. Numerous natural systems contain surfaces or threads that enable directional water transport 1 , 2 , 3 , 4 , 5 , 6 , 7 . This behaviour is usually ascribed to hierarchical structural features at the microscale and nanoscale, with gradients in surface energy 8 , 9 and gradients in Laplace pressure 10 thought to be the main driving forces. Here we study the prey-trapping pitcher organs of the carnivorous plant Nepenthes alata . We find that continuous, directional water transport occurs on the surface of the ‘peristome’—the rim of the pitcher—because of its multiscale structure, which optimizes and enhances capillary rise 11 , 12 in the transport direction, and prevents backflow by pinning in place any water front that is moving in the reverse direction. This results not only in unidirectional flow despite the absence of any surface-energy gradient, but also in a transport speed that is much higher than previously thought. We anticipate that the basic ‘design’ principles underlying this behaviour could be used to develop artificial fluid-transport systems with practical applications.

The mitochondrion is an important sub-cellular organelle responsible for the cellular energetic source and processes. Owing to its unique sensitivity to heat and reactive oxygen species, the mitochondrion is an appropriate target for photothermal and photodynamic treatment for cancer. However, targeted delivery of therapeutics to mitochondria remains a great challenge due to their location in the sub-cellular compartment and complexity of the intracellular environment. Herein, we report a class of the mitochondrion-targeted liposomal delivery platform consisting of a guanidinium-based dendritic peptide moiety mimicking mitochondrion protein transmembrane signaling to exert mitochondrion-targeted delivery with pH sensitive and charge-reversible functions to enhance tumor accumulation and cell penetration. Compared to the current triphenylphosphonium (TPP)-based mitochondrion targeting system, this dendritic lipopeptide (DLP) liposomal delivery platform exhibits about 3.7-fold higher mitochondrion-targeted delivery efficacy. Complete tumor eradication is demonstrated in mice bearing 4T1 mammary tumors after combined photothermal and photodynamic therapies delivered by the reported DLP platform. Mitochondria are key targets for photothermal and photodynamic treatment for cancer but delivery of therapeutics to these organelles remains a challenge. In this study, authors develop a mitochondrial targeted liposomal delivery platform using a dendritic peptide moiety as a mitochondria targeting moiety and demonstrate its targeting and antitumour efficacy in a mouse model of breast cancer.

The main pathological mechanism of intervertebral disc degeneration (IVDD) is the programmed apoptosis of nucleus pulposus (NP) cells. Oxidative stress is a significant cause of IVDD. Whether mitophagy is induced by strong oxidative stress in IVDD remains to be determined. This study aimed to investigate the relationship between oxidative stress and mitophagy and to better understand the mechanism of IVDD in vivo and in vitro. To this end, we obtained primary NP cells from the human NP and subsequently exposed them to TBHP. We observed that oxidative stress induced mitophagy to cause apoptosis in NP cells, and we suppressed mitophagy and found that NP cells were protected against apoptosis. Interestingly, TBHP resulted in mitophagy through the inhibition of the HIF-1α/NDUFA4L2 pathway. Therefore, the upregulation of mitochondrial NDUFA4L2 restricted mitophagy induced by oxidative stress. Furthermore, the expression levels of HIF-1α and NDUFA4L2 were decreased in human IVDD. In conclusion, these results demonstrated that the upregulation of NDUFA4L2 ameliorated the apoptosis of NP cells by repressing excessive mitophagy, which ultimately alleviated IVDD. These findings show for the first time that NDUFA4L2 and mitophagy may be potential therapeutic targets for IVDD. Disc degeneration: Mitochondria at the root of the problem A study in rats highlights the role of mitochondria in intervertebral disc degeneration (IVDD), one of the most important and prevalent predisposing factors for lower back pain. Previous studies have shown that in IVDD, oxidative stress results in the gradual loss of cells in the inner part of vertebral discs which cushion the space between vertebrae. Sheng-Dan Jiang and Lei-Sheng Jiang at Shanghai Jiaotong University School of Medicine found that oxidative stress in these cells causes the selective degradation of mitochondria by preventing the expression of a protein that is essential for mitochondrial function. Overexpressing this protein in the intervertebral discs of rats with IVDD alleviated degeneration, suggesting that restoring mitochondrial function could be an effective therapeutic strategy for easing the pain associated with the condition.

Polyglutamine (polyQ) expansion of proteins can trigger protein misfolding and amyloid-like aggregation, which thus lead to severe cytotoxicities and even the respective neurodegenerative diseases. However, why polyQ aggregation is toxic to cells is not fully elucidated. Here, we took the fragments of polyQ-expanded (PQE) ataxin-7 (Atx7) and huntingtin (Htt) as models to investigate the effect of polyQ aggregates on the cellular proteostasis of endogenous ataxin-3 (Atx3), a protein that frequently appears in diverse inclusion bodies. We found that PQE Atx7 and Htt impair the cellular proteostasis of Atx3 by reducing its soluble as well as total Atx3 level but enhancing formation of the aggregates. Expression of these polyQ proteins promotes proteasomal degradation of endogenous Atx3 and accumulation of its aggregated form. Then we verified that the co-chaperone HSJ1 is an essential factor that orchestrates the balance of cellular proteostasis of Atx3; and further discovered that the polyQ proteins can sequester HSJ1 into aggregates or inclusions in a UIM domain-dependent manner. Thereby, the impairment of Atx3 proteostasis may be attributed to the sequestration and functional loss of cellular HSJ1. This study deciphers a potential mechanism underlying how PQE protein triggers proteinopathies, and also provides additional evidence in supporting the hijacking hypothesis that sequestration of cellular interacting partners by protein aggregates leads to cytotoxicity or neurodegeneration.

China has been suffering from serious air pollution for years in response to the rapid industrialization and urbanization. Notably Beijing is one of the most polluted capitals in the world. Hence, the focus of the study area is on Beijing. In the first stage, we analyze spatial and temporal characteristics of air pollution of the 6 cities while in the second stage the Granger causality test is applied to investigate whether air pollution of a city is affected by its neighbors, and vice versa. The findings are the following. Overall, AQI values are high in winter and early spring while low in summer and autumn. Among the 6 cities, Baoding is the major contributor to air pollution in this entire area. Besides, Granger causality test results show that there is a unidirectional relationship running from Baoding to Beijing and a bidirectional relationship between Beijing and Tianjin. In other words, apart from local air pollutants, for example, exhaust gas, air quality of Beijing is affected by air pollution of Tianjin, and vice versa. However, regarding the relationship between Beijing and Baoding, air quality of Beijing is just affected by air pollution of Baoding, since Baoding is much polluted than Beijing.

The emerging heterogeneous membranes show unprecedented superiority in harvesting the osmotic energy between ionic solutions of different salinity. However, the power densities are limited by the low interfacial transport efficiency caused by a mismatch of pore alignment and insufficient coupling between channels of different dimensions. Here we demonstrate the use of three-dimensional (3D) gel interface to achieve high-performance osmotic energy conversion through hybridizing polyelectrolyte hydrogel and aramid nanofiber membrane. The ionic diode effect of the heterogeneous membrane facilitates one-way ion diffusion, and the gel layer provides a charged 3D transport network, greatly enhancing the interfacial transport efficiency. When used for harvesting the osmotic energy from the mixing of sea and river water, the heterogeneous membrane outperforms the state-of-the-art membranes, to the best of our knowledge, with power densities of 5.06 W m −2 . The diversity of the polyelectrolyte and gel makes our strategy a potentially universal approach for osmotic energy conversion. Heterogeneous membranes show great promise in harvesting the osmotic energy, but the performance is limited by the low interfacial transport efficiency. Here, the authors report use of a three-dimensional polyelectrolyte gel interface to achieve high-performance osmotic energy conversion.