Open structure and gating of the Arabidopsis mechanosensitive ion channel MSL10

Plants are challenged by drastically different osmotic environments during growth and development. Adaptation to these environments often involves mechanosensitive ion channels that can detect and respond to mechanical force. In the model plant Arabidopsis thaliana, the mechanosensitive channel MSL10 plays a crucial role in hypo-osmotic shock adaptation and programmed cell death induction, but the molecular basis of channel function remains poorly understood. Here, we report a structural and electrophysiological analysis of MSL10. The cryo-electron microscopy structures reveal a distinct heptameric channel assembly. Structures of the wild-type channel in detergent and lipid environments, and in the absence of membrane tension, capture an open conformation. Furthermore, structural analysis of a non-conductive mutant channel demonstrates that reorientation of phenylalanine side chains alone, without main chain rearrangements, may generate the hydrophobic gate. Together, these results reveal a distinct gating mechanism and advance our understanding of mechanotransduction

Intragraft Selection of the T Cell Receptor Repertoire by Class I MHC Sequences in Tolerant Recipients

Background: Allograft tolerance of ACI (RT1 a) recipients to WF (RT1 u) hearts can be induced by allochimeric class I MHC molecules containing donor-type (RT1A u) immunogenic epitopes displayed on recipient-type (RT1A a) sequences. Here, we sought the mechanisms by which allochimeric sequences may affect responding T cells through T cell receptor (TCA) repertoire restriction. Methodology/Principal Findings: The soluble [a1h u]-RT1.A a allochimeric molecule was delivered into ACI recipients of WF hearts in the presence of sub-therapeutic dose of cyclosporine (CsA). The TCR Vb spectrotyping of the splenocytes and cardiac allografts showed that the Vb gene families were differentially expressed within the TCR repertoire in allochimericor high-dose CsA-treated tolerant recipients at day +5 and +7 of post-transplantation. However, at day 30 of posttransplantation the allochimeric molecule-treated rats showed the restriction of TCR repertoire with altered dominant size peaks representing preferential clonal expansion of Vb7, Vb11, Vb13, Vb 14, and Vb15 genes. Moreover, we found a positive correlation between the alteration of Vb profile, restriction of TCR repertoire, and the establishment of allograft tolerance. Conclusions: Our findings indicate that presentation of allochimeric MHC class I sequences that partially mimic donor an

Structural mechanism for gating of a eukaryotic mechanosensitive channel of small conductance

Mechanosensitive ion channels transduce physical force into electrochemical signaling that underlies an array of fundamental physiological processes, including hearing, touch, proprioception, osmoregulation, and morphogenesis. The mechanosensitive channels of small conductance (MscS) constitute a remarkably diverse superfamily of channels critical for management of osmotic pressure. Here, we present cryo-electron microscopy structures of a MscS homolog from Arabidopsis thaliana, MSL1, presumably in both the closed and open states. The heptameric MSL1 channel contains an unusual bowl-shaped transmembrane region, which is reminiscent of the evolutionarily and architecturally unrelated mechanosensitive Piezo channels. Upon channel opening, the curved transmembrane domain of MSL1 flattens and expands. Our structures, in combination with functional analyses, delineate a structural mechanism by which mechanosensitive channels open under increased membrane tension. Further, the shared structural feature between unrelated channels suggests the possibility of a unified mechanical gating mechanism stemming from membrane deformation induced by a non-planar transmembrane domain

Psychometric properties of the Chinese version Fear of Cancer Recurrence Questionnaire-7 (FCR-7)

Funding: President Foundation of Nanfang Hospital, Southern Medical University (2017L001); Guangzhou Science and Technology Project (201804010132); Key Item of Guangzhou bureau of education (2019KC106), and Innovation Item of Guangdong Provincial Department of Education (2018A043442).This article investigates the reliability and validity of the Chinese version of the 7-item Fear of Cancer Recurrence Questionnaire (FCR-7). A total of 1,025 cancer patients were recruited and asked to complete the Chinese FCR-7, Fear of Progression Questionnaire—Short Form (FoP-Q–SF), 9-item Patient Health Questionnaire (PHQ-9), and 7-item General Anxiety Disorder Questionnaire (GAD-7). The internal consistency and test–retest reliabilities were examined. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted on random split-half samples. Overall relationships of FCR-7 with other psychological constructs were examined. The Chinese FCR-7 showed good internal consistency (Cronbach’s alpha = .87), test–retest reliability (r = .90), and item–total correlations (range = .583–.872). The unitary factor structure was supported by the EFA and the CFA fit statistics (comparative fit index = .99, root-mean-square error of approximation = .039, 95% confidence interval [.01, .07]). The total score of FCR-7 was positively associated with FoP-Q–SF (r = .756, p < .01), PHQ-9 (r = .522, p < .01), and GAD-7 (r = .553, p < .01). Patients with low monthly income (p < .001) and family cancer history (p = .012) and those who had gone through chemotherapy (p = .001) tended to report higher fear of cancer recurrence (FCR). The FCR-7 has been translated and successfully culturally adapted into a Chinese version. It is a reliable and valid measurement for assessing FCR.PostprintPeer reviewe

Ligand and G-protein selectivity in the κ-opioid receptor

The κ-opioid receptor (KOR) represents a highly desirable therapeutic target for treating not only pain but also addiction and affective disorder

Phosphorylation of Icariin Can Alleviate the Oxidative Stress Caused by the Duck Hepatitis Virus A through Mitogen-Activated Protein Kinases Signaling Pathways

The duck virus hepatitis (DVH) caused by the duck hepatitis virus A (DHAV) has produced extensive economic losses to the duck industry. The currently licensed commercial vaccine has shown some defects and does not completely prevent the DVH. Accordingly, a new alternative treatment for this disease is urgently needed. Previous studies have shown that icariin (ICA) and its phosphorylated derivative (pICA) possessed good anti-DHAV effects through direct and indirect antiviral pathways, such as antioxidative stress. But the antioxidant activity showed some differences between ICA and pICA. The aim of this study is to prove that ICA and pICA attenuate oxidative stress caused by DHAV in vitro and in vivo, and to investigate their mechanism of action to explain their differences in antioxidant activities. In vivo, the dynamic deaths, oxidative evaluation indexes and hepatic pathological change scores were detected. When was added the hinokitiol which showed the pro-oxidative effect as an intervention method, pICA still possessed more treatment effect than ICA. The strong correlation between mortality and oxidative stress proves that ICA and pICA alleviate oxidative stress caused by DHAV. This was also demonstrated by the addition of hydrogen peroxide (H2O2) as an intervention method in vitro. pICA can be more effective than ICA to improve duck embryonic hepatocytes (DEHs) viability and reduce the virulence of DHAV. The strong correlation between TCID50 and oxidative stress demonstrates that ICA and pICA can achieve anti-DHAV effects by inhibiting oxidative stress. In addition, the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) of ICA and pICA showed significant difference. pICA could significantly inhibit the phosphorylation of p38, extra cellular signal regulated Kinase (ERK 1/2) and c-Jun N-terminal kinase (JNK), which were related to mitogen-activated protein kinases (MAPKs) signaling pathways. Ultimately, compared to ICA, pICA exhibited more antioxidant activity that could regulate oxidative stress-related indicators, and inhibited the phosphorylation of MAPKs signaling pathway

Human ACE2‑Functionalized Gold “Virus‑Trap” Nanostructures for Accurate Capture of SARS‑CoV‑2 and Single‑Virus SERS Detection

The current COVID-19 pandemic urges the extremely sensitive and prompt detection of SARS-CoV-2 virus. Here, we present a Human Angiotensin-converting-enzyme 2 (ACE2)-functionalized gold “virus traps” nanostructure as an extremely sensitive SERS biosensor, to selectively capture and rapidly detect S-protein expressed coronavirus, such as the current SARS-CoV-2 in the contaminated water, down to the single-virus level. Such a SERS sensor features extraordinary 106- fold virus enrichment originating from high-affinity of ACE2 with S protein as well as “virus-traps” composed of oblique gold nanoneedles, and 109- fold enhancement of Raman signals originating from multicomponent SERS effects. Furthermore, the identification standard of virus signals is established by machine-learning and identification techniques, resulting in an especially low detection limit of 80 copies mL− 1 for the simulated contaminated water by SARS-CoV-2 virus with complex circumstance as short as 5 min, which is of great significance for achieving real-time monitoring and early warning of coronavirus. Moreover, here-developed method can be used to establish the identification standard for future unknown coronavirus, and immediately enable extremely sensitive and rapid detection of novel virus

Source and Evolution of Subduction–Related Hot Springs Discharged in Tengchong Geothermal Field, Southwest China: Constrained by Stable H, O, and Mg Isotopes

The hydrothermal system plays a crucial role in material and energy cycling between the lithosphere and hydrosphere. In general, seafloor hydrothermal systems are one of important Mg sinks, but the situation may not be the same as it is in terrestrial hydrothermal systems. In addition, the behavior of Mg isotopes during hydrothermal circulation is still unclear. Thus, in this study, we determined the Mg isotopic compositions of the hydrothermal fluids discharged in the Tengchong region to understand better the fate of Mg in the continental hydrothermal system. The δ2H and δ18O values of the Tengchong hydrothermal fluids indicate that the recharge water sources are primary from meteoric water and influenced by the evaporation process. In contrast, the subduction–related volcanic water input is limited, except in for the Rehai area. The Mg in most of the samples is contributed by percolated meteoric water. The measured δ26Mg values range from –0.969 to 0.173‰, which are enriched in light Mg compared to the volcanic rocks of Tengchong. Combined with the precipitation dissolution of carbonate, we calculated the δ26Mg value for the endmember fluid before precipitation, which shows that the process of carbonate precipitation changes the Mg isotope of the fluid, substantially. The Shiqiang (SQ) vent is unique among all of the samples, characterized by an extremely a high δ26Mg value and Mg concentration, and it is estimated that it could have been mixed with an upper crustal material. This also reveals the diversity of the hydrothermal fluid material sources in the subduction zone

Controllable Synthesis of 2D Perovskite on Different Substrates and Its Application as Photodetector

Perovskites have recently attracted intense interests for optoelectronic devices application due to their excellent photovoltaic and photoelectric properties. The performance of perovskite-based devices highly depends on the perovskite material properties. However, the widely used spin-coating method can only prepare polycrystalline perovskite and physical vapor deposition (PVD) method requires a higher melting point (&gt;350 &deg;C) substrate due to the high growth temperature, which is not suitable for low melting point substrates, especially for flexible substrates. Here, we present the controlled synthesis of high quality two-dimensional (2D) perovskite platelets on random substrates, including SiO2/Si, Si, mica, glass and flexible polydimethylsiloxane (PDMS) substrates, and our method is applicable to any substrate as long as its melting point is higher than 100 &deg;C. We found that the photoluminescence (PL) characteristics of perovskite depend strongly on the platelets thickness, namely, thicker perovskite platelet has higher PL wavelength and stronger intensity, and thinner perovskite exhibits opposite results. Moreover, photodetectors based on the as-produced perovskite platelets show excellent photoelectric performance with a high photoresponsivity of 8.3 A&middot;W&minus;1, a high on/off ratio of ~103, and a small rise and decay time of 30 and 50 ms, respectively. Our approach in this work provides a feasible way for making 2D perovskite platelets for wide optoelectronic applications