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The latest meta-analysis indicated potential survival benefits from ultra-short-acting β-blockers in patients with sepsis with persistent tachycardia. However, subsequent multicenter randomized controlled trials (RCTs) have reported conflicting findings, prompting the need for an updated meta-analysis to incorporate these newly published RCTs.

Unbalanced current distribution in cable-in-conduit conductors (CICCs) is a phenomenon that shows the dependence of stability performance on the ramp rate (ramp-rate limitation) in fusion magnets. In this study, we investigated the effect of the twist pitches of the cable stages in a CICC on the current distribution among its strands. We calculated the self-inductance of each strand and the mutual inductance between strands based on a geometrical model that analytically computes the strand's trajectory. Then, we created an equivalent circuit model and calculated the current distribution in the CICC. The current distribution was analyzed for CICCs with different twist pitch configurations. The result shows that combining the cabling stage twist pitches affects the current distribution.

BackgroundHypertrophic cardiomyopathy (HCM) is often concomitant with sleep-disordered breathing (SDB), which can cause adverse cardiovascular events. Although an appropriate approach to SDB prevents cardiac remodelling, detection of concomitant SDB in patients with HCM remains suboptimal. Thus, we aimed to develop a machine learning-based discriminant model for SDB in HCM.MethodsIn the present multicentre study, we consecutively registered patients with HCM and performed nocturnal oximetry. The outcome was a high Oxygen Desaturation Index (ODI), defined as 3% ODI >10, which significantly correlated with the presence of moderate or severe SDB. We randomly divided the whole participants into a training set (80%) and a test set (20%). With data from the training set, we developed a random forest discriminant model for high ODI based on clinical parameters. We tested the ability of the discriminant model on the test set and compared it with a previous logistic regression model for distinguishing SDB in patients with HCM.ResultsAmong 369 patients with HCM, 228 (61.8%) had high ODI. In the test set, the area under the receiver operating characteristic curve of the discriminant model was 0.86 (95% CI 0.77 to 0.94). The sensitivity was 0.91 (95% CI 0.79 to 0.98) and specificity was 0.68 (95% CI 0.48 to 0.84). When the test set was divided into low-probability and high-probability groups, the high-probability group had a higher prevalence of high ODI than the low-probability group (82.4% vs 17.4%, OR 20.9 (95% CI 5.3 to 105.8), Fisher’s exact test p<0.001). The discriminant model significantly outperformed the previous logistic regression model (DeLong test p=0.03).ConclusionsOur study serves as the first to develop a machine learning-based discriminant model for the concomitance of SDB in patients with HCM. The discriminant model may facilitate cost-effective screening tests and treatments for SDB in the population with HCM.

Idiopathic inflammatory myopathies (IIMs) are a heterogeneous group characterized by muscle weakness and skin symptoms and are categorized into six subtypes: dermatomyositis (DM), polymyositis (PM), anti-synthetase syndrome (ASS), immune-mediated myopathy (IMNM), inclusion body myopathy (IBM), and overlap myositis. Myositis-specific autoantibodies were detected for the diagnosis and classification of IIM. This review highlights the pathogenic contributions of the complement system, microangiopathy, and inflammation in IIM. Deposition of complement around capillaries and/or the sarcolemma was observed in muscle biopsy specimens from patients with DM, ASS, and IMNM, suggesting the pathomechanism of complement-dependent muscle and endothelial cell injury. A recent study using human muscle microvascular endothelial cells showed that Jo-1 antibodies from ASS induce complement-dependent cellular cytotoxicity in vitro. Based on both clinical and pathological observations, antibody- and complement-mediated microangiopathy may contribute to the development of DM and anti-Jo-1 ASS. Juvenile DM is characterized by the loss of capillaries, perivascular inflammation, and small-vessel angiopathies, which may be related to microinfarction and perifascicular atrophy. Several serum biomarkers that reflect the IFN1 signature and microangiopathy are elevated in patients with DM. The pathological observation of myxovirus resistance protein A (MxA), which suggests a type 1 interferon (IFN1) signature in DM, supports the diagnosis and further understanding of the pathomechanism of IIM. A recent report showed that an increase in triggering receptor expressed on myeloid cells (TREM-1) around perimysial blood vessels and muscles in patients with IIM plays a role in triggering inflammation and promoting the migration of inflammatory cells by secreting proinflammatory cytokines, such as tumor necrosis factor α. The deposition of complement in muscles and capillaries is a characteristic feature of DM, ASS, and IMNM. Microangiopathy plays a pathogenic role in DM, possibly resulting in perifascicular atrophy. Further understanding of the detailed pathomechanism regarding complement, microangiopathy, and inflammation may lead to novel therapeutic approaches for IIM.

Three-phase coaxial high-temperature superconducting (HTS) cables have three layers, and HTS conductors are arranged circularly in each layer. Since each arranged conductor transports current, the conductor arrangement determines the magnetic field distribution inside the cable. In addition, the AC loss varies depending on the conductor arrangement because the magnitude of the perpendicular magnetic field on each conductor determines the AC loss of the cable. Therefore, it is essential to consider the optimal conductor arrangement in cable design. In this study, we investigated the influence of the relative position of the conductors constituting each phase on the AC losses. The conductors constituting the cable were Y-based superconducting conductors, and the AC losses were calculated by one-dimension finite element analysis of the T-method. The calculation results show that shortening the gap between conductors in the radial direction reduces the AC loss. Furthermore, we have shown that simultaneously shortening the circumferential and radial gap between conductors can significantly reduce AC losses. In addition, the cost estimation shows that it is essential to consider a conductor arrangement with low AC losses in cable design.

In polymer electrolyte type fuel cells, the platinum-based catalysts are applied for the oxygen reduction reaction. However, the specific adsorption from the sulfo group in perfluorosulfonic acid ionomers has been considered to passivate the active sites of the platinum. Herein, we present platinum catalysts covered by an ultrathin two-dimensional nitrogen-doped carbon shell (CNx) layer to protect the platinum from the specific adsorption of perfluorosulfonic acid ionomers. Such coated catalysts were obtained by the facile polydopamine coating method, which is available to tune the thickness of the carbon shell by tuning the polymerization time. The coated catalysts that possess a CNxwith a thickness of 1.5 nm demonstrated superior ORR activity and comparable oxygen diffusivity when compared to the commercial Pt/C. These results were supported by the changes in the electronic statements observed in the X-ray photoelectron spectroscopy (XPS) and CO stripping analyses. Furthermore, the oxygen coverage, CO displacement charge, and operandoX-ray absorption spectroscopy (XAS) tests were employed to identify the protection effect of CNxin coated catalysts compared with the Pt/C catalysts. In summary, the CNxcould not only suppress the oxide species generation but also prevent the specific adsorption of the sulfo group in the ionomer.

Suitable stereostructures of vibrioferrin probes for iron uptake of Vibrio parahaemolyticuswere revealed. Stereoisomers of dansyl labeled vibrioferrin at the 2''-position were synthesized and their uptake activities were evaluated. Vibrio parahaemolyticustakes in both isomers at the 2''-position. In addition to Vibrio parahaemolyticus, several bacteria have also taken up the (R)-isomer.Suitable stereostructures of vibrioferrin probes for iron uptake of Vibrio parahaemolyticuswas revealed. Vibrio parahaemolyticusuptake both stereoisomers of dansyl labeled vibrioferrin at the C2'' position. In addition to Vibrio parahaemolyticus, some bacteria have also taken up the (R)-isomer.

PeQD (Lead tri‐halide perovskite quantum dot) has attracted attention for next generated optical materials due to its excellent optical properties. Herein, we proposed the strategy to precise control and maintain the emission wavelength on PeQD based on the band engineering, and fabricating the LED (light‐emitting diode).

The impact of left ventricular (LV) systolic function on outcomes in patients with sepsis and septic shock remains uncertain. The association, if any, may be nonlinear.

The effect and safety of bivalirudin compared with heparin in patients undergoing extracorporeal membrane oxygenation (ECMO) remains unclear. Therefore, we conducted a systematic review and meta-analysis to compare the effectiveness and safety of heparin and bivalirudin in patients who underwent ECMO. We searched Embase, the Cochrane Central Register of Controlled Trials, and MEDLINE. Inclusion criteria included patients (1) undergoing ECMO and (2) receiving bivalirudin or heparin. We excluded studies where the majority of patients switched heparin to bivalirudin or vice versa during the clinical course. The primary outcome was short-term mortality. We presented the results of all analyses with the use of random-effects models. Eleven studies reported short-term mortality. The use of bivalirudin was associated with significantly lower short-term mortality, compared with heparin (odds ratio: 0.71, 95% confidence interval, 0.55–0.92; p= 0.01, I2= 7%). In this meta-analysis of observational studies, the use of bivalirudin was associated with significantly lower short-term mortality, compared with heparin. Further prospective studies are warranted to clarify this finding.

Right ventricular injury (RVI) in respiratory failure receiving veno-venous extracorporeal membrane oxygenation (VV ECMO) is associated with significant mortality. A scoping review is necessary to map the current literature and guide future research regarding the definition and management of RVI in patients receiving VV ECMO. We searched for relevant publications on RVI in patients receiving VV ECMO in Medline, EMBASE, and Web of Science. Of 1,868 citations screened, 30 studies reported on RVI (inclusive of right ventricular dilation, right ventricular dysfunction, and right ventricular failure) during VV ECMO. Twenty-three studies reported on the definition of RVI including echocardiographic indices of RV function and dimensions, whereas 13 studies reported on the management of RVI, including veno-pulmonary (VP) ECMO, veno-arterial (VA) ECMO, positive inotropic agents, pulmonary vasodilators, ultra-lung-protective ventilation (Ultra-LPV), and optimization of positive end-expiratory pressure (PEEP). The definitions of RVI in patients receiving VV ECMO used in the literature are heterogeneous. Despite the high incidence of RVI during VV ECMO support and its strong association with mortality, studies investigating therapeutic strategies for RVI are also lacking. To fill the existing knowledge gaps, a consensus on the definition of RVI and research investigating RV-targeted therapies during VV ECMO is urgently warranted.

Stimulator of interferon genes (STING) is essential for the type I interferon response against a variety of DNA pathogens. Upon emergence of cytosolic DNA, STING translocates from the endoplasmic reticulum to the Golgi where STING activates the downstream kinase TBK1, then to lysosome through recycling endosomes (REs) for its degradation. Although the molecular machinery of STING activation is extensively studied and defined, the one underlying STING degradation and inactivation has not yet been fully elucidated. Here we show that STING is degraded by the endosomal sorting complexes required for transport (ESCRT)-driven microautophagy. Airyscan super-resolution microscopy and correlative light/electron microscopy suggest that STING-positive vesicles of an RE origin are directly encapsulated into Lamp1-positive compartments. Screening of mammalian Vpsgenes, the yeast homologues of which regulate Golgi-to-vacuole transport, shows that ESCRT proteins are essential for the STING encapsulation into Lamp1-positive compartments. Knockdown of Tsg101 and Vps4, components of ESCRT, results in the accumulation of STING vesicles in the cytosol, leading to the sustained type I interferon response. Knockdown of Tsg101 in human primary T cells leads to an increase the expression of interferon-stimulated genes. STING undergoes K63-linked ubiquitination at lysine 288 during its transit through the Golgi/REs, and this ubiquitination is required for STING degradation. Our results reveal a molecular mechanism that prevents hyperactivation of innate immune signalling, which operates at REs.

An investigation of unprecedented crystal structures enables development of new functions and enhancement of well-known properties.Although an infinite number of crystal structures are geometrically possible, the crystal structures of metal nanoparticles depend on thermodynamics.Mono-metal nanoparticles with ordered stacking faults and ordered point defects, as well as unprecedented ordered alloy nanoparticles, are generated by stabilization.Stabilization is by: (i) transformation from unfavorable to more favorable structures during growth of the nanoparticles and epitaxial growth of other metals on ordered stacking faults structures, (ii) suppression of the atomic diffusion rate, and (iii) substitution of third elements based on the interelement miscibility.

Lead halide perovskite nanocrystals (NCs) have outstanding photoluminescence (PL) properties and excellent potential for light-emitting diodes and single-photon sources. Here, we report the multiple-peak structures originating from excitons, trions, and biexcitons in low-temperature PL spectra of single CsPbBr3NCs. We found fine-structure splitting in the PL peaks of bright excitons and biexcitons and also in the longitudinal–optical (LO)-phonon replicas of excitons. LO-phonon replicas of trions are clearly observed under strong photoexcitation, which do not show fine-structure splitting. From size-dependent analyses of these replicas, we clarified that both exciton–phonon and trion–phonon couplings become larger for smaller NCs and the coupling strengths of trions are larger than those of excitons in large NCs. These behaviors can be explained by the spatial distributions of the electron and hole wave functions in the NCs. Our findings provide essential information on electron–phonon couplings in perovskites and for the design of high-purity single-photon sources.

Objective:Several studies have shown septic shock developing later during the hospital stay is associated with higher mortality. However, the precise point at which time from hospital admission to the onset of septic shock (admission-shock-onset-time) becomes an independent prognostic marker of mortality remains unknown. This study evaluated the association between admission-shock-onset-time and in-hospital mortality among patients with septic shock and the optimal cutoff period to categorize early- and late-onset septic shock. Method:We conducted a single-center retrospective, observational cohort study at a quaternary academic hospital comprising adult patients with septic shock admitted to a medical intensive care unit (ICU) from January 2011 to December 2020. A multivariable additive logistic regression model was developed to assess if log-transformed admission-shock-onset-time was associated with in-hospital mortality. The thin plate spline function was used to describe the nonlinear relationship between the log-transformed admission-shock-onset-time and in-hospital mortality. The primary outcome was in-hospital mortality, and the secondary outcome was ICU mortality. Results:Two thousand five hundred twenty patients met the inclusion criteria with an overall in-hospital mortality of 37.3%. The log-transformed admission-shock-onset-time was associated with higher in-hospital and ICU mortality even after adjusting for clinical variables. The odds ratio for in-hospital mortality continued to increase throughout the observation period. The adjusted odds ratio exceeded 2 in between 20.1 and 54.6 h, and it surpassed 3 in between 54.6 and 148.4 h of the time from the hospital admission to shock onset. Conclusion:In-hospital mortality continued to rise as admission-shock-onset-time increased in patients with septic shock. No clear dichotomization between early and late septic shock could be ascertained, and this categorization may limit our understanding of the temporal relationship of shock onset to mortality.

Since the discovery of high-order harmonic generation (HHG) in solids1–3, much effort has been devoted to understand its generation mechanism and both inter- and intraband transitions are known to be essential1–10. However, intraband transitions are affected by the electronic structure of a solid, and how they contribute to nonlinear carrier generation and HHG remains an open question. Here we use mid-infrared laser pulses to study HHG in CdSe and CdS quantum dots, where quantum confinement can be used to control the intraband transitions. We find that both HHG intensity per excited volume and generated carrier density increase when the average quantum dot size is increased from about 2 to 3 nm. We show that the reduction in sub-bandgap energy in larger quantum dots enhances intraband transitions, and this—in turn—increases the rate of photocarrier injection by coupling with interband transitions, resulting in enhanced HHG.

Quantitative susceptibility mapping (QSM) is an advanced MRI technique for evaluating the distribution of magnetic susceptibility related to substances such as iron, hemosiderin, and deoxyhemoglobin, and there are numerous clinical applications of QSM.

The first total syntheses of two 4,10-dihydroxy-8,12-guaianolides that were reported to be natural products were achieved. Toward the syntheses of a collection of related guaianolides, the typical 5,7-fused system of 8,12-guaianolides was constructed by a ring expansion reaction of a hydroxylated coronafacic acid analogue that can be practically synthesized and optically resolved. The total syntheses of these compounds revealed that the previously reported structures of both natural products were incorrect.

The rapid manufacturing of transparent SiO2glass components via a hybridized 3D structuring approach for photo-curing and green machining, followed by a fast debinding/sintering process (at a heating rate of 20 °C min–1), is reported to be based on the design of a new series of interparticle photo-cross-linkable suspensions. In these suspensions, small amounts of multifunctional acrylates and silane alkoxides with acryloyl groups (A-Si) are co-photo-polymerized and further reacted with SiO2particles modified using functionalized polyethyleneimine to form hybridized interparticle networks. The addition of A-Si increases the interparticle cross-linking densities, leading to an improvement in the mechanical properties and green machinability of the photo-cured bodies. Furthermore, the A-Si component in the cross-links forms siloxane-based networks among SiO2particles in situduring the debinding/sintering process, which increases the mechanical strength of the debinded bodies and successfully prevents structural collapses under rapid heating conditions. The study demonstrates that the photo-cured body from the newly designed suspensions can be green-machined into pillars, microfluids, and assembling blocks and can be sintered into highly transparent SiO2glass components. Overall, this work provides new options for the time- and energy-effective processing of SiO2glass materials with tailor-made 3D structures.

Colloidal crystals (CCs) constructed from inorganic nanoparticle (NP) building blocks exhibit properties that cannot be realized from isolated NPs or corresponding bulk counterparts. Because the arrangement of NPs in CCs is crucial in the CC’s collective properties, development of a procedure to modulate the assembly of NP constituents is important. We demonstrate rapid formation of nickel (phosphide) CCs with tunable crystallinity through van der Waals force-driven spontaneous self-assembly of NPs in a facile one-pot colloidal synthesis. The quantity of size-regulating reagent (tri-n-octylphosphine) modulates the assembly of NPs from ordered close-packed to a disordered configuration in CCs. Synchrotron-based in situsmall-angle X-ray scattering revealed that the size uniformity of the NPs determines the crystallinity of CCs, indicating the importance of regulating the growth kinetics of NPs during the synthesis. Our work will be useful for universal scalable preparation of CCs from a variety of materials and structures, with tunable concerted properties.

Low-acidity polymer electrolyte membranes are essential to polymer electrolyte fuel cells (PEFCs) and water electrolysis systems, both of which are expected to be next-generation energy and hydrogen sources. We developed a new type of high-performance polymer electrolyte membrane (PEM) in which the core particles are precisely electrolyte polymer coated and filled into binder resin. Cellulose nanocrystals (CNCs), which have attracted attention as light, rigid, and sustainable materials, were selected as the core material for the filler. The CNC surface was coated with a new block copolymer containing a proton conductive polymer of poly(vinylphosphonic acid) (PVPA) and a hydrophobic polymer of polystyrene (PS) using RAFT polymerization with particles (PwP) we developed. The pelletized fillers and the filler-filled polycarbonate membranes achieved proton conductivities of over 10–2S/cm with lower activation energies and much weaker acidity than the Nafion membrane.

Lead halide perovskite nanocrystals (NCs) have superior photoluminescence (PL) properties, such as high PL quantum yields and wide PL wavelength tunability, for optoelectronic applications. Here, we report the PL spectra of single formamidinium lead halide perovskite FAPbX3(X = Br, I) NCs examined by single-dot spectroscopy at low temperature. We found four PL peaks in the low-energy region below the strong exciton PL peak that originate from two longitudinal-optical (LO) phonon replicas of the exciton PL, biexcitons, and charged excitons (trions). The binding energies of the biexcitons and trions become larger as the NCs decrease in size. The LO phonon energies show no size dependence, but the Huang–Rhys factors, which reflect the strength of the exciton–phonon coupling, become larger for smaller NCs. Our findings provide important insights into the exciton properties of perovskite NCs.

ABSTRACTObjective: Acute kidney injury (AKI) is associated with higher morbidity and mortality in cardiac arrest (CA). There are limited contemporary data on the incidence and outcomes of AKI in CA.Methods: We comprehensively searched the databases of MEDLINE, EMBASE, PUBMED, and the Cochrane from inception to November 2020. Observational studies that reported the incidence of AKI in CA survivors were included. Data from each study were combined using the random effects to calculate pooled incidence and risk ratios with 95% confidence intervals (CIs). The primary outcome was short-term mortality and secondary outcomes included long-term mortality, incidence of AKI, and use of renal replacement therapy (RRT). Subgroup and meta-regression analyses were performed to explore heterogeneity.Main results: A total of 25 observational studies comprising 8,165 patients were included. The incidence of AKI in CA survivors was 40.3% (range 32.9–47.8%). In stage 3 AKI, one-fourth of patients required RRT. AKI was associated with an increased risk of both short-term (OR 2.27 [95% CI 1.74–2.96]; p< 0.001) and long-term mortality (OR 1.51 [95% CI 1.93–3.25]; p< 0.001). Meta-regression and subgroup analyses did not suggest any effect of hypothermia on incidence of AKI.Conclusion: AKI complicates the care of 40% of CA survivors and is associated with significantly increased short- and long-term mortality.

The predictive value of airway occlusion pressure at 100 milliseconds (P0.1) on weaning outcome has been controversial. We performed a meta-analysis to investigate the predictive value of P0.1 on successful weaning from mechanical ventilation.

Historically, β-blockers have been considered to be relatively contraindicated for septic shock because they may cause cardiac suppression. On the other hand, there is an increasing interest in the use of β-blockers for treating patients with sepsis with persistent tachycardia despite initial resuscitation.

Elaborate chemical synthesis methods allow the production of various types of inorganic nanocrystals (NCs) with uniform shape and size distributions. Many single-step synthesis approaches, such as the reduction of metal ions, the decomposition of metal complexes, double replacement reactions, and hydrolysis, have been adapted to promote the generation of monodisperse metal and ionic NCs. However, the question has become, how can we synthesize NCs with thermodynamically metastable phases or very complex structures? The transformation of already-synthesized NCs via elemental substitutions, such as ion exchange reactions for ionic NCs and galvanic replacement reactions for metal NCs, can overcome the difficulties facing conventional one-step syntheses. In particular, NC ion exchange reactions have been studied with numerous combinations of foreign ions and ionic NCs with various shapes. They have been investigated extensively because the reactions proceed under relatively mild conditions thanks to the large surface-to-volume ratio of the NCs relative to their bulk form. The functionality of the resulting ionic NCs, including semiconducting and plasmonic properties, can be easily tuned in a wide range, from the visible to near-infrared. Because anions generally have much larger ionic radii than cations within the frameworks of NCs, the cation exchange reactions proceed much faster than the anion exchange reactions. For ionic NCs above a critical size, the anion framework remains intact, and the original shape of the parent NCs is retained throughout the cation exchange reaction. In contrast, the anion exchange reaction often provides the new NCs with unique structures, such as hollow or anisotropically phase-segregated assemblies.

Lead halide perovskite nanocrystals (NCs) are a class of promising light-emitting materials and have been considered as gain media in lasers. Strong exciton–exciton interactions in NCs cause an energy shift of the lowest optical transition and affect the optical gain threshold. Here, we clarify the dynamics of exciton–exciton interactions in highly photoexcited CsPbI3NCs by double-pump transient absorption spectroscopy. This method provides control over the population of each excited state by varying the time interval between the two pump pulses. We find that the band-edge energy shift induced by the formation of asymmetric hot-biexcitons (comprising one ground-state exciton and one hot exciton) is smaller than that induced by hot excitons and hot biexcitons in the ensemble. We demonstrate that the generation of asymmetric hot-biexcitons reduces the optical gain threshold in the CsPbI3NC ensemble.

Lead halide perovskite (APbX3) nanocrystals exhibit photoluminescence (PL) with both wide wavelength tunability and high quantum efficiency. While the Pb–X6octahedra mainly determines the near-band-edge optical properties and the A-site cation affects the structural stability, the role of the A-site cation in determining the optical properties is still unclear. Here, we report the PL properties of three types of lead bromide perovskite APbBr3nanocrystals with different cations [A = HC(NH2)2+, CH3NH3+, and Cs+], as revealed by single-dot spectroscopy, and discuss the influence of the A-site cation on the PL spectrum. The nanocrystal size dependences of the PL energy and lifetime show no large variation with the species of the A-site cation. We find that the size of the A-site cation determines the coupling strength between electrons and longitudinal-optical phonons in the nanocrystal and thus affects the PL spectral shape, especially the low-energy tail.

A flow-injection analysis (FIA) method for assaying an anionic surfactant (AS) using AS optode detector was demonstrated. The optode membrane consists of 2-nitrophenyl octyl ether as a plasticizer, lactone form rhodamine B (L-RB) and poly(vinyl chloride). The linear response concentration range of the AS optode to AS was 20 - 100 μmol dm-3 in the FIA system. The sampling rate for an AS ion (40 μmol dm-3 sodium dodecylbenzenesulfonate) in the proposed FIA system was ca.5 samples h-1. The AS level in commercially available laundry detergents by the proposed FIA system was determined.

We synthesized a new Pd(0) complex bearing π-acceptor ligands and a σ-donor ligand and confirmed that it exhibits high air stability and catalytic activity in direct arylation reactions. Moreover, stoichiometric reactions of the complex revealed that the σ-donor ligand does not dissociate from the Pd center.

TLRs respond to a variety of microbial products and initiate defense responses against bacteria and viruses. A variety of pathogens invade into and control the endosomal compartment to survive in host cells. On the other hand, host cells deploy cell surface and endosomal TLRs to pathogen‐containing vesicles to mount defense responses. The endosomal compartment is a site for pathogen‐sensing. As TLR‐dependent defense responses are accompanied with a shift to the anabolic state, TLR responses need to be under metabolic control. Cellular metabolic state is monitored by sensing lysosomal metabolites by the mammalian target of rapamycin complex 1 (mTORC1). Type I IFN production induced by endosomal TLRs requires mTORC1. Recent studies have demonstrated that the interaction between TLRs and mTORC1 depends on their anterograde movement to the cell periphery. In a nutrient‐sufficient state, a molecular complex called Ragulator recruits and activates mTORC1 in lysosomes. In parallel, Ragulator allows the small GTPase Arl8b to drive lysosomes to the cell periphery. Nutrient‐activated mTORC1 in peripheral lysosomes is constitutively associated with type I IFN signaling molecules such as TRAF3 and IKKα. On the other hand, TLR7 and TLR3 are activated in the endosomal compartment and induce trafficking of TLR‐containing vesicles to the cell periphery in a manner dependent on Arl8b or another GTPase Rab7a, respectively. Lysosomal trafficking helps TLR7 and TLR3 to interact with nutrient‐activated mTORC1 and type I IFN signaling molecules. The endosomal compartments serve as platforms where metabolic sensing machinery licenses TLRs to initiate type I IFN responses. Review on how endosomal compartment actively controls interaction between TLRs and metabolic sensors.

Supplemental Digital Content is available in the text.

The synthesis of Sm2Fe17N3magnetic particles has been vigorously studied because of their superior magnetic properties. Here, we developed a novel method to form Sm2Fe17N3magnetic particles with relatively high coercivity (1.3 T), which were formed from Fe3O4–SmOxcore–shell nanoparticles using a reduction-diffusion process, followed by in-situnitridation. This method would provide not only smaller Sm2Fe17N3particles with higher coercivity but also other rare-earth containing materials.The novel nanoparticle approach has been developed to form the Sm2Fe17N3magnetic particles with relatively high coercivity (1.3 T), which were formed from the Fe3O4–SmOxcore–shell nanoparticles using the reduction-diffusion process, followed by in-situnitridation, and would provide us with not only the smaller Sm2Fe17N3particles with higher coercivity but also other rare-earth containing materials.

Microwave-assisted tertiary carbon radical reaction was developed. The reaction of tertiary xanthates with electron deficient alkenes was prompted by microwave irradiation, and various coupling products possessing quaternary carbon centers were obtained in good yields. The reaction was conducted under simple and common radical condition except for microwave irradiation, and the reaction completed within 5 min.Microwave-assisted tertiary carbon radical reaction for construction of quaternary carbon center was developed. The reaction of tertiary xanthates with electron deficient alkenes was prompted by microwave irradiation, and various C-C bond-forming products with the quaternary carbon center were obtained in good yields. The reaction condition is simple and the reaction completes within 5 min.

The major ampullate silk of orb-weaving spiders is renowned for its exceptional mechanical properties, including high tensile strength and extensibility. The development of artificial spider silk presents a promising alternative to traditional fibers with significant environmental impacts. This study aims to elucidate the relationship between sequence motifs of natural spider silk and the mechanical properties of artificial spider silk. Using the Spider Silkome Database, we identified motifs correlated with specific physical properties and substituted them into MaSp2-based mini-spidroin BP1. We then measured the mechanical properties of the resulting recombinant artificial spider silk through tensile tests, observed structural properties via birefringence measurement and wide-angle X-ray scattering, and evaluated the water response through boiled water shrinkage tests. Introducing a positively correlated motif increased the tensile strength by 9.3%, while a negatively correlated motif decreased it by 5.1%, confirming the sequence–property relationship. These findings demonstrate that targeted motif substitution can effectively control the physical properties of artificial spider silk, facilitating the development of sustainable biomaterials with tailored mechanical properties for diverse industrial applications.

Lead halide perovskite nanocrystals (NCs) have attracted much attention as light-source materials for light-emitting diodes, lasers, and quantum light emitters. The luminescence properties of perovskite NCs and the performance of NC-based light-source devices depend on trion and biexciton dynamics. Here, we examined the size dependence of trion and biexciton binding energies by conducting low-temperature single-dot spectroscopy on three different perovskite NCs: CsPbBr3, CsPbI3, and FAPbBr3. While the photoluminescence spectral widths of the all-inorganic CsPbBr3and CsPbI3NCs were narrow, compared with those of the organic–inorganic hybrid FAPbBr3NCs, the binding energies of trions and biexcitons of all three samples showed similar size dependences, independent of the A-site cation and halogen. The effective-mass approximation calculations implied the importance of dynamical dielectric screening on the formation of trions and biexcitons.

Our understanding of hemodynamics in cirrhotic patients with sepsis remains limited. Our study aims to investigate differences in hemodynamic profiles using echocardiography between septic patients with and without cirrhosis.

Low Pt-based alloy catalysts are regarded as an efficient strategy in achieving high activity for the oxygen reduction reaction (ORR) in proton-exchange membrane fuel cells (PEMFCs). However, the desired durability for the low Pt-based catalysts, such as the Pt1Co3catalyst, has still been considered a great challenge for PEMFCs. In this study, we investigate sub-2.5 nm PtxCoyalloy catalysts with varying Co content and Pt1Co3@Pt core–shell (CS) nanostructure catalysts obtained through a simple displacement reaction. The Pt1Co3@Pt_H catalysts showed a high mass activity (MA) of 1.46 A/mgPtat 0.9 V and 14% MA loss after 10k accelerated degradation test (ADT) cycles, which suggested the improved stability compared with Pt1Co3catalysts (52% MA loss). To clarify the degradation mechanism, operandohigh-energy resolution fluorescence detection X-ray absorption spectroscopy (XAS) was applied in addition to conventional advanced measurement techniques, including operandoconventional XAS, to analyze the electronic state and structure changes during operation potentials. We found that introducing Co improves the catalysts’ activity mainly from the strain effect, but an excessive amount of Co leads to increased Pt-oxidation, which accelerates the degradation of the catalysts. The Pt1Co3@Pt_H catalyst shows high tolerance to Pt-oxidation, benefiting both the stability and activity. Our findings demonstrate an in-depth understanding of the degradation mechanism and the importance of designing PtCo CS nanostructures with optimal Co content for enhanced performance in PEMFCs.

ObjectiveDysfunction of the blood–nerve barrier (BNB) plays important roles in chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). The aim of the present study was to identify the candidate cytokines/chemokines that cause the breakdown of the BNB using sera from patients with CIDP and MMN.MethodsWe determined the levels of 27 cytokines and chemokines in human peripheral nerve microvascular endothelial cells (PnMECs) after exposure to sera obtained from patients with CIDP variants (typical CIDP and multifocal acquired demyelinating sensory and motor neuropathy [MADSAM]), MMN and amyotrophic lateral sclerosis (ALS), and healthy controls (HC), using a multiplexed fluorescent bead-based immunoassay system.ResultsThe induced protein (IP)10 level in the cells in both the MADSAM and MMN groups was markedly increased in comparison with the typical CIDP, ALS and HC groups. The other cytokines, including granulocyte colony-stimulating factor,vascular endothelial growth factor (VEGF) and interleukin-7, were also significantly upregulated in the MADSAM group. The increase of IP-10 produced by PnMECs was correlated with the presence of conduction block in both the MADSAM and MMN groups.ConclusionThe autocrine secretion of IP-10 induced by patient sera in PnMECs was markedly upregulated in both the MADSAM and MMN groups. The overproduction of IP-10 by PnMECs leads to the focal breakdown of the BNB and may help to mediate the transfer of pathogenic T cells across the BNB, thereby resulting in the appearance of conduction block in electrophysiological studies of patients with MADSAM and MMN.

TLR3 is a sensor of double-stranded RNA that is indispensable for defense against infection with herpes simplex virus type 1 (HSV-1) in the brain. We found here that TLR3 was required for innate immune responses to HSV-1 in neurons and astrocytes. During infection with HSV-1, TLR3 recruited the metabolic checkpoint kinase complex mTORC2, which led to the induction of chemokines and trafficking of TLR3 to the cell periphery. Such trafficking enabled the activation of molecules (including mTORC1) required for the induction of type I interferons. Intracranial infection of mice with HSV-1 was exacerbated by impairment of TLR3 responses with an inhibitor of mTOR and was significantly ‘rescued’ by potentiation of TLR3 responses with an agonistic antibody to TLR3. These results suggest that the TLR3–mTORC2 axis might be a therapeutic target through which to combat herpes simplex encephalitis. The receptor TLR3 is essential for effective responses to herpes simplex virus type 1. Miyake and colleagues demonstrate that a neuron- and astrocyte-intrinsic pathway of TLR3 and the metabolic checkpoint kinase complex mTORC2 is needed to prevent fulminant infection with this virus and encephalitis.

Lead halide perovskite nanocrystals (NCs) are one of the most anticipated and promising materials for light-emitting diodes and lasers because of their high photoluminescence quantum yields (PLQYs). However, the formation of trions (charged excitons) in the NCs reduces their PLQYs. Here, we clarify the trion formation mechanism in perovskite CsPbBr3NCs by analyzing the excitation fluence dependence of transient absorption signals. Under weak photoexcitation, trions are formed by charge carrier trapping at surface states. In contrast, biexciton Auger recombination dominates the trion formation under strong photoexcitation. We found that the postsynthetic surface treatment suppresses the extrinsic surface-related formation of trions. The thorough understanding of the trion formation mechanisms is essential for the PLQY improvement of perovskite NCs and helps to reduce ionization of NCs in solid-state devices.