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Piezo proteins are bona fide mammalian mechanotransduction channels for various cell types including endothelial cells. The mouse Piezo1 of 2547 residues forms a three-bladed, propeller-like homo-trimer comprising a central pore-module and three propeller-structures that might serve as mechanotransduction-modules. However, the mechanogating and regulation of Piezo channels remain unclear. Here we identify the sarcoplasmic /endoplasmic-reticulum Ca 2+ ATPase (SERCA), including the widely expressed SERCA2, as Piezo interacting proteins. SERCA2 strategically suppresses Piezo1 via acting on a 14-residue-constituted intracellular linker connecting the pore-module and mechanotransduction-module. Mutating the linker impairs mechanogating and SERCA2-mediated modulation of Piezo1. Furthermore, the synthetic linker-peptide disrupts the modulatory effects of SERCA2, demonstrating the key role of the linker in mechanogating and regulation. Importantly, the SERCA2-mediated regulation affects Piezo1-dependent migration of endothelial cells. Collectively, we identify SERCA-mediated regulation of Piezos and the functional significance of the linker, providing important insights into the mechanogating and regulation mechanisms of Piezo channels. Mechanosensitive Piezo channels are important for a wide range of mechanotransduction processes. Here the authors show that Piezos interact with sarcoplasmic /endoplasmic-reticulum Ca 2+ ATPases (SERCA) and give mechanistic insights into mechanogating and SERCA2-mediated regulation of Piezo1.

The mechanosensitive Piezo channels function as key eukaryotic mechanotransducers. However, their structures and mechanogating mechanisms remain unknown. Here we determine the three-bladed, propeller-like electron cryo-microscopy structure of mouse Piezo1 and functionally reveal its mechanotransduction components. Despite the lack of sequence repetition, we identify nine repetitive units consisting of four transmembrane helices each—which we term transmembrane helical units (THUs)—which assemble into a highly curved blade-like structure. The last transmembrane helix encloses a hydrophobic pore, followed by three intracellular fenestration sites and side portals that contain pore-property-determining residues. The central region forms a 90?Å-long intracellular beam-like structure, which undergoes a lever-like motion to connect THUs to the pore via the interfaces of the C-terminal domain, the anchor-resembling domain and the outer helix. Deleting extracellular loops in the distal THUs or mutating single residues in the beam impairs the mechanical activation of Piezo1. Overall, Piezo1 possesses a unique 38-transmembrane-helix topology and designated mechanotransduction components, which enable a lever-like mechanogating mechanism. The electron cryo-microscopy structure of full-length mouse Piezo1 reveals unique topological features such as the repetitive transmembrane helical units that constitute the highly curved transmembrane region, and identifies regions and single residues that are crucial for the mechanical activation of the channel. Structure and mechanism of ion channel Piezo1 Mechanosensitive cation channels convert external mechanical stimuli into various biological actions, including touch, hearing, balance and cardiovascular regulation. The eukaryotic Piezo proteins are mechanotransduction channels, although their structure and gating mechanisms are not well elucidated. In related papers in this issue of Nature , two groups report cryo-electron microscopy structures of the full-length mouse Piezo1 and reveal three flexible propeller blades. Each blade is made up of at least 26 helices, forming a series of helical bundles, which adopt a curved transmembrane region. A kinked beam and anchor domain link these Piezo repeats to the pore, giving clues as to how the channel responds to membrane tension and mechanical force.

Hypertension has emerged as a serious global health issue and piqued the interest of academics all over the world. Angiotensin-I converting enzyme (ACE, EC 3.4.15.1) plays a crucial role in blood pressure regulation. Due to their safety and mildness compared with synthetic drugs, natural bioactive inhibitory peptides against ACE generated from various protein sources cause an upsurge of research and development. Spirulina platensis is a cyanobacterium widely distributed in aquaculture and an ideal protein source for bioactive peptide production, owing to its remarkable protein content and nutritive value. In this study, novel ACE inhibitory peptides from Spirulina platensis protein hydrolysates digested by commercial thermolysin were isolated by membrane filtration and size exclusion-high-performance liquid chromatography (SEC-HPLC) in sequence, and identified by mass spectrum analysis and ACE inhibitory activity assay. The results showed that two novel ACE inhibitory peptides were obtained, and their amino acid sequences were Val–Thr–Tyr (VTY) and Leu–Gly–Val–Pro (LGVP), with IC50 values of 23.39 µM, and 45.76 µM, respectively. Molecular docking analysis indicated that the VTY was mainly bound in the S1 and S2 active pockets of ACE via hydrogen bonds, while LGVP only partially interacted with the S1 pocket. Our findings provide novel insights for the development of ACE inhibitors and the high-value utilization of Spirulina platensis.

Comparing the outcomes of video-laryngoscopy and flexible fiberoptic bronchoscopy for endotracheal intubation in patients with cervical spine immobilization. All of the comparative studies published in the PubMed, Cochrane Library, Medline, Web of Science, and EMBASE databases as of 8 Jan 2024 were included. All outcomes were analyzed using Review Manager 5.4. The primary outcomes were the successful first-attempt intubation rate, intubation time, heart rate after intubation, mean arterial pressure after intubation, overall intubation success rate, risk of tissue damage and sore throat. The meta-analysis included six randomized controlled studies with a total of 694 patients. The outcomes of the meta-analysis revealed that the use of video laryngoscopy was better than flexible fiberoptic bronchoscopy in terms of the successful first-attempt intubation rate (P<0.05) and intubation time (P<0.05) in patients with cervical spine immobilization. However, there were no statistically significant differences in heart rate after intubation, mean arterial pressure after intubation, overall intubation success rate, risk of tissue damage, or sore throat (all P>0.05) between the video laryngoscopy and flexible fiberoptic bronchoscopy groups. Compared with flexible fiberoptic bronchoscopy, video laryngoscopy has superior tracheal intubation performance in terms of the first-attempt success rate and intubation speed. This finding was observed in patients with cervical spine immobilization who utilized a cervical collar to simulate a difficult airway. Additionally, both types of scopes demonstrated similar complication rates. Current evidence suggests that video laryngoscopy is better suited than flexible fiberoptic bronchoscopy for endotracheal intubation in patients immobilized with a cervical collar. Systematic review protocol: CRD42024499868.

Purpose The clinical outcomes of patients who received a cervical collar after anterior cervical decompression and fusion were evaluated by comparison with those of patients who did not receive a cervical collar. Methods All of the comparative studies published in the PubMed, Cochrane Library, Medline, Web of Science, and EMBASE databases as of 1 October 2023 were included. All outcomes were analysed using Review Manager 5.4. Results Four studies with a total of 406 patients were included, and three of the studies were randomized controlled trials. Meta-analysis of the short-form 36 results revealed that wearing a cervical collar after anterior cervical decompression and fusion was more beneficial ( P  < 0.05). However, it is important to note that when considering the Neck Disability Index at the final follow-up visit, not wearing a cervical collar was found to be more advantageous. There were no statistically significant differences in postoperative cervical range of motion, fusion rate, or neck disability index at 6 weeks postoperatively (all P  > 0.05) between the cervical collar group and the no cervical collar group. Conclusions This systematic review and meta-analysis revealed no significant differences in the 6-week postoperative cervical range of motion, fusion rate, or neck disability index between the cervical collar group and the no cervical collar group. However, compared to patients who did not wear a cervical collar, patients who did wear a cervical collar had better scores on the short form 36. Interestingly, at the final follow-up visit, the neck disability index scores were better in the no cervical collar group than in the cervical collar group. PROSPERO registration number: CRD42023466583.

Purpose The clinical outcomes of using a zero-profile for anterior cervical decompression and fusion were evaluated by comparison with anterior cervical plates. Methods All of the comparative studies published in the PubMed, Cochrane Library, Medline, Web of Science, EBSOChost, and EMBASE databases as of 1 October 2021 were included. All outcomes were analysed using Review Manager 5.4. Results Seven randomized controlled studies were included with a total of 528 patients, and all studies were randomized controlled studies. The meta-analysis outcomes indicated that the use of zero-profile fixation for anterior cervical decompression and fusion was better than anterior cervical plate fixation regarding the incidence of postoperative dysphagia ( P  < 0.05), adjacent-level ossification ( P  < 0.05), and operational time ( P  < 0.05). However, there were no statistically significant differences in intraoperative blood loss, Visual Analogue Scale, Neck Disability Index, or Japanese Orthopaedic Association scale (all P  > 0.05) between the zero-profile and anterior cervical plate groups. Conclusions The systematic review and meta-analysis indicated that zero-profile and anterior cervical plates could result in good postoperative outcomes in anterior cervical decompression and fusion. No significant differences were found in intraoperative blood loss, Visual Analogue Scale, Neck Disability Index, or Japanese Orthopaedic Association scale . However, the zero-profile is superior to the anterior cervical plate in the following measures: incidence of postoperative dysphagia, adjacent-level ossification, and operational time. PROSPERO registration CRD42021278214.

On 13 December 2012, Chang'e-2 conducted a successful flyby of the near-Earth asteroid 4179 Toutatis at a closest distance of 770 ± 120 meters from the asteroid's surface. The highest-resolution image, with a resolution of better than 3 meters, reveals new discoveries on the asteroid, e.g., a giant basin at the big end, a sharply perpendicular silhouette near the neck region and direct evidence of boulders and regolith, which suggests that Toutatis may bear a rubble-pile structure. Toutatis' maximum physical length and width are (4.75 × 1.95 km) ±10%, respectively and the direction of the + z axis is estimated to be (250 ± 5°, 63 ± 5°) with respect to the J2000 ecliptic coordinate system. The bifurcated configuration is indicative of a contact binary origin for Toutatis, which is composed of two lobes (head and body). Chang'e-2 observations have significantly improved our understanding of the characteristics, formation and evolution of asteroids in general.

How follicular T-helper （Tfh） cells develop is incom- pletely understood. We find that, upon antigen exposure in vivo, both naive and antigen-experienced T cells sequentially upregulate CXCR5 and Bc16 within the first 24 h, relocate to the T-B border, and give rise to phenotypic Bcl6＋CXCR5＋ Tfh cells before the first cell division. CXCR5 upregulation is more dependent on ICOS costimulation than that of Bcl6, and early Bcl6 induction requires T-cell expression of CXCR5 and, presumably, relocation toward the follicle. This early and rapid upregulation of CXCR5 and Bcl6 depends on IL-6 produced by radiation-resistant cells. These results suggest that a Bcl6hiCXCR5hi phenotype does not automatically define a Tfh lineage but might reflect a state of antigen exposure and non-commitment to terminal effector fates and that niches in the T-B border and/or the follicle are important for optimal Bcl6 induction and maintenance.

Purpose The clinical outcomes of using a cortical screw (CS) for lumbar interbody fusion were evaluated by comparison with conventional pedicle screw (PS) fixation. Methods All of the comparative studies published in the PubMed, Cochrane Library, MEDLINE, Web of Science, and EMBASE databases recently as 18 March 2019, were included. All outcomes were analyzed by using Review Manager 5.3. Results Twelve studies were included with a total of 835 patients, and two of the studies were randomized controlled trials. The outcomes of the meta-analysis indicated that the use of CS fixation for lumbar interbody fusion was better than conventional PS fixation in regard to operating time ( p  = 0.02), intraoperative blood loss ( p  < 0.00001), length of stay ( p  = 0.02), incidence of complications ( p  = 0.02), adjacent segmental disease (ASD) incidence ( p  = 0.03), and Oswestry Disability Index (ODI) ( p  = 0.03). However, there were no statistically significant differences in the back and leg pain visual analog scale (VAS), Japanese Orthopaedic Association (JOA) scale, and intervertebral fusion rate (all p  > 0.05) between the CS fixation group and the PS fixation group. Conclusions Based on this systematic review and meta-analysis, our outcomes indicated that both CS and conventional PS can result in good postoperative outcomes in lumbar interbody fusion. No significant differences were found in the back and leg pain VAS, JOA scale, and intervertebral fusion rate. However, CS fixation is superior to PS fixation in the following measures: operating time, intraoperative blood loss, length of stay, incidence of complications, ASD incidence, and ODI. Trial registration PROSPERO registration number is CRD 42019132226 .

Purpose The clinical outcomes of using a tubular microdiscectomy for lumbar disc herniation were evaluated by comparison with conventional microdiscectomy. Methods All of the comparative studies published in the PubMed, Cochrane Library, Medline, Web of Science, and EMBASE databases as of 1 May 2023 were included. All outcomes were analysed using Review Manager 5.4. Results This meta-analysis included four randomized controlled studies with a total of 523 patients. The results showed that using tubular microdiscectomy for lumbar disc herniation was more effective than conventional microdiscectomy in improving the Oswestry Disability Index ( P  < 0.05). However, there were no significant differences in operating time, intraoperative blood loss, hospital stay, Visual Analogue Scale, reoperation rate, postoperative recurrence rate, dural tear incidence, and complications rate (all P  > 0.05) between the tubular microdiscectomy and conventional microdiscectomy groups. Conclusions Based on our meta-analysis, it was found that the tubular microdiscectomy group had better outcomes than the conventional microdiscectomy group in terms of Oswestry Disability Index. However, there were no significant differences between the two groups in terms of operating time, intraoperative blood loss, hospital stay, Visual Analogue Scale, reoperation rate, postoperative recurrence rate, dural tear incidence, and complications rate. Current research suggests that tubular microdiscectomy can achieve clinical results similar to those of conventional microdiscectomy. PROSPERO registration number  is: CRD42023407995.