Mechanism of Membrane Curvature Induced by SNX1: Insights from Molecular Dynamics Simulations.

SNX proteins have been found to induce membrane remodeling to facilitate the generation of transport carriers in endosomal pathways. However, the molecular mechanism of membrane bending and the role of lipids in the bending process remain elusive. Here, we conducted coarse-grained molecular dynamics simulations to investigate the role of the three structural modules (PX, BAR, and AH) of SNX1 and the PI3P lipids in membrane deformation. We observed that the presence of all three domains is essential for SNX1 to achieve a stable membrane deformation. BAR is capable of remodeling the membrane through the charged residues on its concave surface, but it requires PX and AH to establish stable membrane binding. AH penetrates into the lipid membrane, thereby promoting the induction of membrane curvature; however, it is inadequate on its own to maintain membrane bending. PI3P lipids are also indispensable for membrane remodeling, as they play a dominant role in the interactions of lipids with the BAR domain. Our results enhance the comprehension of the molecular mechanism underlying SNX1-induced membrane curvature and help future studies of curvature-inducing proteins.

Protective effect of naringin against radiation-induced heart disease in rats via Sirt1/NF-κB signaling pathway and endoplasmic reticulum stress.

This study was designed to explore the protective effect and mechanism of naringin (NG) on radiation-induced heart disease (RIHD) in rats. Rats were divided into four x-ray (XR) irradiation groups with different absorbed doses (0/10/15/20 Gy), or into three groups (control, XR, and XR + NG groups). Subsequently, the ultrasonic diagnostic apparatus was adopted to assess and compare the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular internal diameter at end diastole (LVIDd), and left ventricular internal diameter at end systole (LVIDs) in rats. Hematoxylin-eosin (H&E) staining and Masson staining were applied to detect the pathological damage and fibrosis of heart tissue. Western blot was used to measure the expression levels of myocardial fibrosis-related proteins, endoplasmic reticulum stress-related proteins, and Sirt1 (silent information regulator 1)/NF-κB (nuclear factor kappa-B) signaling pathway-related proteins in cardiac tissues. Additionally, enzyme-linked immunosorbent assay was utilized to detect the activities of pro-inflammatory cytokines, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) in cardiac tissue. The results showed that NG treatment significantly attenuated the 20 Gy XR-induced decline of LVEF and LVFS and the elevation of LVIDs. Cardiac tissue damage and fibrosis caused by 20 Gy XR were significant improved after NG treatment. Meanwhile, in rats irradiated by XR, marked downregulation was identified in the expressions of fibrosis-related proteins (Col I, collagen type I; α-SMA, α-smooth muscle actin; and TGF-ß1, transforming growth factor-beta 1) and endoplasmic reticulum stress-related proteins (GRP78, glucose regulatory protein 78; CHOP, C/EBP homologous protein; ATF6, activating transcription factor 6; and caspase 12) after NG treatment. Moreover, NG treatment also inhibited the production of pro-inflammatory cytokines [interleukin-6, interleukin-1ß, and monocyte chemoattractant protein-1 (MCP-1)], reduced the expression of MDA, and promoted the activities of SOD and CAT. Also, NG treatment promoted Sirt1 expression and inhibited p65 phosphorylation. Collectively, XR irradiation induced cardiac injury in rats in a dose-dependent manner. NG could improve the cardiac injury induced by XR irradiation by inhibiting endoplasmic reticulum stress and activating Sirt1/NF-κB signaling pathway.

Effect of rectal indomethacin on the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography for choledocholithiasis: a prospective randomized clinical trial.

BACKGROUND AND AIM: the aim of this study was to evaluate the efficacy and safety of rectal indomethacin for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in patients with common bile duct (CBD) stones. METHODS: a total of 167 patients undergoing ERCP between November 2019 and November 2022 for CBD stones in the First Affiliated Hospital of Dalian Medical University were prospectively analyzed. The patients were divided into an indomethacin group (n = 58) and a control group (n = 109). The primary endpoint was the percent of patients who experienced PEP. RESULTS: PEP was observed in a total of 26 patients (15.57 %); four patients (6.90 %) in the indomethacin group and 22 (20.18 %) in the control group (p = 0.042). Mild, moderate and severe PEP was observed in three (5.17 %), one (1.72 %) and zero patients, respectively, in the indomethacin group, and in eleven (10.09 %), nine (8.26 %) and two (1.83 %) patients, respectively, in the control group. There was one case (0.92 %) of death due to PEP in the control group. No cases of moderate or severe bleeding were observed in either group. CONCLUSIONS: rectal indomethacin is an effective and safe method to prevent PEP for patients with CBD stones undergoing ERCP.

Diversity and genetic characterization of orthohantavirus from small mammals and humans during 2012-2022 in Hubei Province, Central China.

Hemorrhagic fever with renal syndrome (HFRS) is a significant public health problem in Hubei Province, China, where a novel strain of orthohantavirus, HV004, was reported in 2012. However, no systematic study has investigated the prevalence and variation of orthohantavirus in rodents and humans. Herein, 2137 small mammals were collected from ten HFRS epidemic areas in Hubei Province from 2012 to 2022, and 143 serum samples from patients with suspected hemorrhagic fever were collected from two hospitals from 2017 to 2021. Orthohantavirus RNA was recovered from 134 lung tissue samples from five rodent species, with a 6.27 % prevalence, and orthohantavirus was detected in serum samples from 25 patients. Genetic analyses revealed that orthohantavirus hantanense (HTNV), orthohantavirus seoulense (SEOV), and orthohantavirus dabieshanense (DBSV) are co-circulating in rodents in Hubei, and HTNV and SEOV were identified in patient serum. Phylogenetic analysis showed that most of the HTNV sequences were clustered with HV004, indicating that HV004-like orthohantavirus was the main HNTV subtype in rodents. Two genetic reassortments and six recombination events were observed in Hubei orthohantaviruses. In summary, this study identified the diversity of orthohantaviruses circulating in Hubei over the past decade, with the HV004-like subtype being the main genotype in rodents and patients. These findings highlight the need for continued attention and focus on orthohantaviruses, especially concerning newly identified strains.

Effect of rectal indomethacin on the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography for choledocholithiasis: a prospective randomized clinical trial

Background and aim: the aim of this study was to evaluate the efficacy and safety of rectal indomethacin for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in patients with common bile duct (CBD) stones. Methods: a total of 167 patients undergoing ERCP between November 2019 and November 2022 for CBD stones in the First Affiliated Hospital of Dalian Medical University were prospectively analyzed. The patients were divided into an indomethacin group (n = 58) and a control group (n = 109). The primary endpoint was the percent of patients who experienced PEP. Results: PEP was observed in a total of 26 patients (15.57 %); four patients (6.90 %) in the indomethacin group and 22 (20.18 %) in the control group (p = 0.042). Mild, moderate and severe PEP was observed in three (5.17 %), one (1.72 %) and zero patients, respectively, in the indomethacin group, and in eleven (10.09 %), nine (8.26 %) and two (1.83 %) patients, respectively, in the control group. There was one case (0.92 %) of death due to PEP in the control group. No cases of moderate or severe bleeding were observed in either group. Conclusions: rectal indomethacin is an effective and safe method to prevent PEP for patients with CBD stones undergoing ERCP. (AU)

Molecular mechanisms of integrin αvß8 activation regulated by graphene, boron nitride and black phosphorus nanosheets.

Integrin αvß8 is a heterodimeric transmembrane protein on macrophages. Nanosheets can activate the integrin and elicit immune responses, exhibiting adverse immunotoxicity. Understanding the mechanism of integrin activation regulated by nanosheets is crucial for safe and effective use of nanosheets in biomedical applications. Herein, we performed all-atom molecular dynamics simulations to clarify the interactions between integrin αvß8 in the cell membrane and three types of nanosheets, graphene (GRA), hexagonal boron nitride (BN), and black phosphorus (BP). We observed that BP could adsorb the intracellular end of αv monomer and thus break the inner membrane clasp, an important hydrophobic cluster for maintaining the inactive state of integrin. The association between αv and ß8 subunit is weakened, promoting the integrin activation. By contrast, GRA and BN exert little influence on the association state of the integrin. Interestingly, the puckered structure of BP affects the integrin activation, where BP with the armchair direction perpendicular to the membrane plane cannot unpack the integrin. Moreover, the perturbation effect of nanosheets on the membrane was also evaluated. BP shows a milder effect on membrane structures and lipid properties than GRA and BN. This work unravels the molecular basis on the activation of integrin mediated by three nanosheets, and suggests the toxicity and therapeutic effect of well-established nanomaterials in the immune system.

An Innovative Insight into Performance Degradation of NCM111 Cathode Induced by Suspension of Operation.

The lifespan of lithium-ion batteries varies enormously from fundamental study to practical applications. This big difference has been typically ascribed to the high degree of uncertainty in unpredictable and complicated operation conditions in real-life applications. Here, we report that the pause of the charging-discharging process, which is frequently operated in practice but rarely studied in academics, is an important reason for the performance degradation of the NCM111 cathode. It is found that the pause during cycling could trigger a remarkable drop in capacity, giving rise to ∼30% more capacity decay compared with the continuously cycled sample. In situ synchrotron X-ray diffraction analysis reveals that the harmful H1-H2 phase transition, which typically appears in the initial cycle but disappears in subsequent cycles, is reactivated by the pausing process. The anisotropic lattice strains that occur during the H1-H2 transition result in mechanical fractures that terminate with an inert NiO-type rock-salt phase on the surface of particles. The present study indicates that the discontinuous usage of rechargeable batteries is also a key factor for cycle life, which might provide a distinct perspective on the performance decay in practical applications.

Unravelling the Interfacial Dynamics of Bandgap Funneling in Bismuth-Based Halide Perovskites.

An environmentally friendly mixed-halide perovskite MA3 Bi2 Cl9- x Ix with a bandgap funnel structure has been developed. However, the dynamic interfacial interactions of bandgap funneling in MA3 Bi2 Cl9- x Ix perovskites in the photoelectrochemical (PEC) system remain ambiguous. In light of this, single- and mixed-halide lead-free bismuth-based hybrid perovskites-MA3 Bi2 Cl9- y Iy and MA3 Bi2 I9 (named MBCl-I and MBI)-in the presence and absence of the bandgap funnel structure, respectively, are prepared. Using temperature-dependent transient photoluminescence and electrochemical voltammetric techniques, the photophysical and (photo)electrochemical phenomena of solid-solid and solid-liquid interfaces for MBCl-I and MBI halide perovskites are therefore confirmed. Concerning the mixed-halide hybrid perovskites MBCl-I with a bandgap funnel structure, stronger electronic coupling arising from an enhanced overlap of electronic wavefunctions results in more efficient exciton transport. Besides, MBCl-I's effective diffusion coefficient and electron-transfer rate demonstrate efficient heterogeneous charge transfer at the solid-liquid interface, generating improved photoelectrochemical hydrogen production. Consequently, this combination of photophysical and electrochemical techniques opens up an avenue to explore the intrinsic and interfacial properties of semiconductor materials for elucidating the correlation between material characterization and device performance.

Creating two-dimensional solid helium via diamond lattice confinement.

The universe abounds with solid helium in polymorphic forms. Therefore, exploring the allotropes of helium remains vital to our understanding of nature. However, it is challenging to produce, observe and utilize solid helium on the earth because high-pressure techniques are required to solidify helium. Here we report the discovery of room-temperature two-dimensional solid helium through the diamond lattice confinement effect. Controllable ion implantation enables the self-assembly of monolayer helium atoms between {100} diamond lattice planes. Using state-of-the-art integrated differential phase contrast microscopy, we decipher the buckled tetragonal arrangement of solid helium monolayers with an anisotropic nature compressed by the robust diamond lattice. These distinctive helium monolayers, in turn, produce substantial compressive strains to the surrounded diamond lattice, resulting in a large-scale bandgap narrowing up to ~2.2 electron volts. This approach opens up new avenues for steerable manipulation of solid helium for achieving intrinsic strain doping with profound applications.

Achieving thermally stable nanoparticles in chemically complex alloys via controllable sluggish lattice diffusion.

Nanoparticle strengthening provides a crucial basis for developing high-performance structural materials with potentially superb mechanical properties for structural applications. However, the general wisdom often fails to work well due to the poor thermal stability of nanoparticles, and the rapid coarsening of these particles will lead to the accelerated failures of these materials especially at elevated temperatures. Here, we demonstrate a strategy to achieve ultra-stable nanoparticles at 800~1000 °C in a Ni59.9-xCoxFe13Cr15Al6Ti6B0.1 (at.%) chemically complex alloy, resulting from the controllable sluggish lattice diffusion (SLD) effect. Our diffusion kinetic simulations reveal that the Co element leads to a significant reduction in the interdiffusion coefficients of all the main elements, especially for the Al element, with a maximum of up to 5 orders of magnitude. Utilizing first-principles calculations, we further unveil the incompressibility of Al induced by the increased concentration of Co plays a critical role in controlling the SLD effect. These findings are useful for providing advances in the design of novel structural alloys with extraordinary property-microstructure stability combinations for structural applications.

3D Upconversion Barcodes for Combinatory Wireless Neuromodulation in Behaving Animals.

Upconversion techniques offer all-optical wireless alternatives to modulate targeted neurons in behaving animals, but most existing upconversion-based optogenetic devices show prefixed emission that is used to excite just one channelrhodopsin at a restricted brain region. Here, a hierarchical upconversion device is reported to enable spatially selective and combinatory optogenetics in behaving rodent animals. The device assumes a multiarrayed optrode format containing engineered upconversion nanoparticles (UCNPs) to deliver dynamic light palettes as a function of excitation wavelength. Three primary emissions at 477, 540, and 654 nm are selected to match the absorption of different channelrhodopsins. The UCNPs are barcode assembled to multiple nanomachined optical pinholes in a microscale pipette device to allow remotely addressable, spectrum programmable, and spatially selective optical interrogation of complex brain circuits. Using the unique device, the basolateral amygdala and caudoputamen circuits are selectively modulated and the associated fear or anxiety behavior in freely behaving rodents is successfully differentiated. It is believed that the 3D barcode upconversion device would be a great supplement to current optogenetic toolsets and opens up new possibilities for sophisticated neural control.

Evolution Characteristics and Clinical Significance of Blood Separation in Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the evolution of blood separation results by gel extraction of multiple myeloma (MM) patients, and to evaluate the clinical value of abnormal blood separation results for the evaluation of disease and prognosis.@*METHODS@#The clinical data of 5 patients diagnosed newly MM patients with abnormal blood separation of gel collection vessels in our hospital were retrospectively analyzed, and the changes of blood separation results and blood index levels were followed up with the improvement of treatment effect, and the correlation of different blood index levels was analyzed.@*RESULTS@#In 5 patients with newly diagnosed MM, the blood separation result showed floating phenomenon after centrifugation, which divided into three layers and the order from top to bottom is separator gel, serum, and red blood cells(RBC). With partial remission of clinical symptoms, the blood separation results were still abnormal, which were divided into three layers from top to bottom: serum, RBC and separator gel. Finally, with complete remission of the disease, blood separation results returned to normal, from top to bottom: serum, separator gel, RBC. With the blood separation results from abnormal to normal, the blood routine indicators: Hb, Hct levels gradually increased, neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR) gradually decreased; biochemical indexes: TP, GLB, Ig and β2-MG levels gradually decreased. Tumor load related indicators: serum IL-6, TNF-α, IL-17 levels gradually decreased, and IL-35 levels gradually increased; and the differences were statistically significant (P<0.05). Pearson correlation analysis showed that serum β2-MG was positively correlated with IL-6, TNF-α and IL-17 levels (r=0.710, 0.756, 0.581, P<0.05), and negatively correlated with IL-35 level (r=-0565, P<0.05).@*CONCLUSION@#Abnormal blood separation exists in MM patients, and there are significant differences in blood, tumor load and immune balance related indexes in patients with different blood separation results, which provides partial experimental basis for evaluation of disease, efficacy and prognosis with different blood separation results.

Pressure-Sensitive Adhesive with Enhanced and Phototunable Underwater Adhesion.

Pressure-sensitive adhesives (PSAs) are extensively used in diverse applications such as semiconductor manufacturing, labeling, and healthcare because of their quick and viscoelasticity-driven physical adhesion to dry surfaces. However, most of the existing PSAs normally fail to maintain or even establish adhesion under harsh conditions, particularly underwater, due to the lack of robust chemical functionalities for chemistry-based adhesion. Meanwhile, these PSAs are incapable of altering the adhesion in response to external stimuli, limiting their employment in applications requiring dynamic adhesion. Here, we develop a chemically functionalized PSA (f-PSA) with enhanced and phototunable underwater adhesion by incorporating an underwater adhesion enhancer (i.e., mussel-inspired catechol) and a photoresponsive functionality (i.e., anthracene) into a standard acrylic PSA matrix. The synergistic coupling of viscoelasticity-driven physical adhesion originating from the matrix with catechol-enabled chemical adhesion secures sufficient interfacial molecular interactions and leads to enhanced underwater adhesion. The efficient dimerization of anthracene via light-triggered cycloaddition facilely mediates the viscoelastic property of f-PSA, rendering the phototunable adhesion. We envision that this f-PSA can open up more opportunities for applications such as underwater manipulation, transfer printing, and medical adhesives.

3D architected temperature-tolerant organohydrogels with ultra-tunable energy absorption.

The properties of mechanical metamaterials such as strength and energy absorption are often "locked" upon being manufactured. While there have been attempts to achieve tunable mechanical properties, state-of-the-art approaches still cannot achieve high strength/energy absorption with versatile tunability simultaneously. Herein, we fabricate for the first time, 3D architected organohydrogels with specific energy absorption that is readily tunable in an unprecedented range up to 5 × 103 (from 0.0035 to 18.5 J g-1) by leveraging on the energy dissipation induced by the synergistic combination of hydrogen bonding and metal coordination. The 3D architected organohydrogels also possess anti-freezing and non-drying properties facilitated by the hydrogen bonding between ethylene glycol and water. In a broader perspective, this work demonstrates a new type of architected metamaterials with the ability to produce a large range of mechanical properties using only a single material system, pushing forward the applications of mechanical metamaterials to broader possibilities.

Stacking Fault Driven Phase Transformation in CrCoNi Medium Entropy Alloy.

Phase transformation is an effective means to increase the ductility of a material. However, even for a commonly observed face-centered-cubic to hexagonal-close-packed (fcc-to-hcp) phase transformation, the underlying mechanisms are far from being settled. In fact, different transformation pathways have been proposed, especially with regard to nucleation of the hcp phase at the nanoscale. In CrCoNi, a so-called medium-entropy alloy, an fcc-to-hcp phase transformation has long been anticipated. Here, we report an in situ loading study with neutron diffraction, which revealed a bulk fcc-to-hcp phase transformation in CrCoNi at 15 K under tensile loading. By correlating deformation characteristics of the fcc phase with the development of the hcp phase, it is shown that the nucleation of the hcp phase was triggered by intrinsic stacking faults. The confirmation of a bulk phase transformation adds to the myriads of deformation mechanisms available in CrCoNi, which together underpin the unusually large ductility at low temperatures.

[Influence of MRD Status in Newly Diagnosed MM Patients with VGPR and Above after Treatment on Clinical Prognosis].

OBJECTIVE: To investigate the influence of MRD status in newly diagnosed MM patients with VGPR and above after treatment on clinical prognosis. METHODS: Clinical data of 210 newly diagnosed MM patients with VGPR and above after treatment in Fifth People's Hospital of Chendu city. from January 2010 to January 2018 were collected and retrospectively analyzed. The patients were divided into 2 groups: group A (152 patients with MRD-) and group B (58 patients with MRD+). The influencing factors of progression free survival and overall survival of patients were analyzed, and the correlation between MRD status and high-risk cytogenetic abnormalities, treatment plan and response to treatment were evaluated. RESULTS: There were no significant difference in clinical characteristics between the patients in 2 groups (P＞0.05). Single factor analysis showed that ASCT and MRD status were related with progression free survival of patients with newly diagnosed MM (P＜0.05). Multivariate analysis by Cox regression model showed that MRD+ persistence was the independent risk factor for progression free survival of patients with newly diagnosed MM (P＜0.05). The cumulative progression free survival rate in 2-year with follow-up of patients in group A was significantly higher than that in B group (P＜0.05). The median progression free survival time and overall survival time of patients with persistent MRD- were significantly longer than those of MRD+ (P＜0.05). The single factor analysis showed that MRD- maintenance time was the influencing factor of PFS and OS time of newly diagnosed MM patients (P＜0.05). The cumulative overall survival rate in 2-year with follow-up of patients with MRD- maintenance for 6 months was significantly higher than that of patients with MRD- maintenance for＜6 months (P＜0.05). The cumulative progression free survival rate and overall survival rate in 2 years with follow-up of patients with MRD- maintenance for ≥12 months were significantly higher than those of MRD-maintenance for ＜12 months（P＜0.05）. The median progression free survival time of patients with MRD- was significantly longer than that of patients with MRD+ who had≥ one kind of high-risk cytogenetic abnormality (P＜0.05). The MRD- rate of patients received ASCT was significantly higher than that of patients without ASCT (P＜0.05). The median progression free survival time of patients with MRD- was significantly longer than that of patients with MRD+ (P＜0.05). The maintenance time of MRD- in patients with bortezomib treatment was significantly longer than that of patients without bortezomib treatment in population with MRD- (P＜0.05). The median progression free survival time of patients with bortezomib treatment was significantly longer than patients without bortezomib treatment (P＜0.05). CONCLUSION: MRD+ maintenance in newly diagnosed MM patients with VGPR and above after treatment closely relates with poor long-term prognosis, however, the MRD- maintenance time can be used for prognosis evaluation. MRD+ suggests that patients possess the possibility of early recurrence, and dynamic monitoring of MRD status in treatment can be helpful to clinical determination of treatment opportunity for relapsed MM patients.

Prognostic value of pretreatment contrast-enhanced computed tomography in esophageal neuroendocrine carcinoma: A multi-center follow-up study.

BACKGROUND: The rare incidence of esophageal neuroendocrine carcinoma (NEC) and limited treatment experience result in insufficient clinical observations and unsuitable guidelines for its management. AIM: To investigate the prognostic value of pretreatment contrast-enhanced computed tomography (CT) characteristics in patients with esophageal NEC. METHODS: Seventy-seven esophageal NEC patients who received contrast-enhanced CT at two hospitals were enrolled in this study from June 2014 to December 2019. The clinical features and image characteristics were recorded accordingly. Univariate survival analysis was performed using the Kaplan-Meier method and log-rank test, and multivariate analysis was carried out with a Cox proportional hazards model. RESULTS: The multivariate analysis performed using the Cox proportional hazards model showed that N stage, adjuvant chemotherapy, and degree of enhancement were independent prognostic factors for overall survival (OS). Meanwhile, adjuvant chemotherapy was an independent prognostic factor for progression-free survival (PFS). The hazard ratios (HRs) of N stage, adjuvant chemotherapy, and degree of enhancement (mild vs moderate/marked) for OS were 0.426 (P = 0.024), 3.862 (P = 0.006), and 2.169/0.809 (P = 0.037), respectively. The HR of adjuvant chemotherapy for PFS was 6.432 (P < 0.001). Adjuvant chemotherapy was significantly associated with degree of enhancement (P = 0.018). CONCLUSION: Adjuvant chemotherapy is an independent prognostic factor for OS and PFS. Additionally, N stage and degree of enhancement are prognostic factors for OS in patients with esophageal NEC.

Counterintuitive Ballistic and Directional Liquid Transport on a Flexible Droplet Rectifier.

Achieving the directional and long-range droplet transport on solid surfaces is widely preferred for many practical applications but has proven to be challenging. Particularly, directionality and transport distance of droplets on hydrophobic surfaces are mutually exclusive. Here, we report that drain fly, a ubiquitous insect maintaining nonwetting property even in very high humidity, develops a unique ballistic droplet transport mechanism to meet these demanding challenges. The drain fly serves as a flexible rectifier to allow for a directional and long-range propagation as well as self-removal of a droplet, thus suppressing unwanted liquid flooding. Further investigation reveals that this phenomenon is owing to the synergistic conjunction of multiscale roughness, structural periodicity, and flexibility, which rectifies the random and localized droplet nucleation (nanoscale and microscale) into a directed and global migration (millimeter-scale). The mechanism we have identified opens up a new approach toward the design of artificial rectifiers for broad applications.

Exosomal miR-145-5p derived from orthohantavirus-infected endothelial cells inhibits HTNV infection.

Human infection of orthohantavirus can cause potentially fatal diseases, such as hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus (HTNV) in Eurasia. Exosomes are new carriers for information exchange between cells. Cumulative findings suggest that exosomes released from parental infected cells can block or promote viral infection in recipient cells, but the role of exosomes in hantavirus infection is poorly understood. In our study, we identified the exosomes derived from HTNV-infected human vascular endothelial cells (HUVECs) (Exo-HV) and found the antiviral properties of Exo-HV in the uninfected recipient cells. High-throughput sequencing revealed the distinctly expressed miRNAs transcriptomes in Exo-HV. MiR-145-5p, one of the abundant miRNAs packaged into Exo-HV, was found to be able to transferred to recipient cells and functioned by directly targeting M RNA of HTNV 76-118 and inducing type I interferon (IFN-I) response, thus, blocking the viral replication. Concluding, this study indicated that exosomes released by HTNV-infected HUVECs were able to transfer active molecules, miR-145-5p as a proving sample, to mediate novel anti-HTNV activity in the neighboring uninfected cells, which will help us to explore new strategies for the treatment of infectious disease utilizing exosomes with miRNA.

Molecular Epidemiology and Vaccine Compatibility Analysis of Seasonal Influenza Viruses in Wuhan, 2016-2019.

Influenza viruses (FLUV) cause high morbidity and mortality annually in the world and pose a serious threat to the public health. Wuhan, as an important transportation hub in China, has a dense population and suitable climate, which also lays a major hidden danger for the outbreak of influenza. To survey and characterize the seasonal FLUV in Wuhan during 2016-2019, we collected 44,738 throat swabs, among which 15.5% were influenza A (FLUAV) positive, 6.1% influenza B (FLUBV) and 0.3% co-infection. By monitoring FLUV in each month from June 2016 to May 2019, different with the previously seasonality pattern, only a single influenza peak was appeared in winter of 2017-2018 and 2018-2019, respectively. These data indicated that the complex circulation pattern of seasonal influenza in Wuhan. In addition, we found the age group was skewed towards 5-14 years group whose activity were mostly school based, which suggested school may be an important place for influenza outbreaks. Meanwhile, phylogenic analysis revealed that two subtypes (subclade 3C.2a2 and 3C.2a1b) of A(H3N2) were circulating in Wuhan and there was an obvious transition in 2018 because the two subclades were detected simultaneously. Furthermore, by estimating the vaccine effectiveness, we found that the vaccine strain of FLUAV didn't seem to match very well the current epidemic strain, especially A(H3N2). Hence, more accurate prediction of seasonal outbreak is essential for vaccine design. Taken together, our results provided the current information about seasonal FLUV in Wuhan which form the basis for vaccine updating.