Membrane-disrupting agents that selectively target virus versus host membranes could potentially inhibit a broad-spectrum of enveloped viruses, but currently such antivirals are lacking. Here, we ...develop a nanodisc incorporated with a decoy virus receptor that inhibits virus infection. Mechanistically, nanodiscs carrying the viral receptor sialic acid bind to influenza virions and are co-endocytosed into host cells. At low pH in the endosome, the nanodiscs rupture the viral envelope, trapping viral RNAs inside the endolysosome for enzymatic decomposition. In contrast, liposomes containing a decoy receptor show weak antiviral activity due to the lack of membrane disruption. The nanodiscs inhibit influenza virus infection and reduce morbidity and mortality in a mouse model. Our results suggest a new class of antivirals applicable to other enveloped viruses that cause irreversible physical damage specifically to virus envelope by viruses' own fusion machine. In conclusion, the lipid nanostructure provides another dimension for antiviral activity of decoy molecules.
To evaluate for correlation between MRI paraspinous muscle (PSM) enhancement and clinical measures of cirrhosis severity (CMCS) utilizing established imaging biomarkers of sarcopenia as comparison. ...Retrospective evaluation of 224 patients (mean age 59.6± 9.7 years, 135 males and 89 females) with liver cirrhosis who underwent contrast-enhanced MRI between August 2021 and August 2022 was performed. Assessed variables included: body mass index (BMI), varices and ascites present on imaging (VPI and API), albumin, total bilirubin (Tbili), international normalized ratio (INR), creatinine, MELD score, as well as history of paracentesis (PH), spontaneous bacterial peritonitis, and variceal bleed (VBH). These variables were compared to PSM skeletal muscle index (SMI), PSM signal fat fractions (sFF), and PSM contrast enhancement fraction (CEFR) calculated on arterial (CEFR-ART), portal venous (CEFR-PV), and delayed (CEFR-DEL) phases collected on MRI. PSM CEFR is significantly reduced on MRI in patients with clinical manifestations of severe liver cirrhosis. Further investigation into PSM CEFR's usefulness as an imaging biomarker for evaluating liver disease severity is warranted.
Various sediment properties, such as mean grain size, total organic carbon, total nitrogen, C/N ratio, CaCO3, and biogenic opal content, were analyzed for a box core (BC02; 45 cm long) and a gravity ...core (GC02; 628 cm long), which were collected from the western margin of the Hupo Trough located off the eastern coast of Korea. The study area has been affected by the East Korea Warm Current (EKWC), a branch of the Tsushima Warm Current (TWC). The analytical results obtained for BC02 and the upper part of GC02 were in agreement, affirming the core-top preservation of GC02. Based on the corrected calibrated AMS 14C dates, the sedimentation rate of GC02 changed abruptly at ~8.2 ka from ~4.0–10.2 cm/kyr in the lower part to ~56.6–91.0 cm/kyr in the middle to upper part. This corresponds to the lithologic change from sandy mud to mud sediments showing the mean grain size change from 6.9 to 46.0 μm. Diverse paleoceanographic proxies representing the surface water condition exhibited varying degree of change at ~8.2 ka, after which all the properties remain almost unchanged, implying stable and continuous depositional conditions following the complete development of the EKWC. Furthermore, it indicated that the sediment depositional conditions in the Hupo Trough in response to the EKWC might have stabilized at ~8.2 ka since the opening of the Korea Strait during the Holocene sea level rise. Moreover, microfossil data from previous studies on the establishment of the TWC in the East Sea (Japan Sea) support our interpretation that the sediment properties revealed the Holocene development of the EKWC in the Hupo Trough.
This study examined the effects of alloying elements such as Re and Ta on the microstructural evolution of recrystallized W under proton (1 MeV H+) and self-ion (18 MeV W6+) irradiations at 800 °C. ...Although the number density of voids increased with increasing proton-induced damage level, the void density in W-Re (R) and W-Ta (R) alloys were lower than that of pure W (R). Herein, the addition of Re and Ta to W suppresses the void formation process. In the proton-irradiated W-3%Re (R), a lot of dislocation loops were observed at 0.05 dpa which is the stage of nucleation. The evolution process up to 0.2 dpa was characterized by loop growth via the absorption of clusters and point defects. The dislocation loops then coalesce and grow large, and the dislocation lines become tangled at 1 dpa. At 0.05 dpa, the dislocation loops in pure W (R) have already evolved into the tangled dislocations. Solute Re may inhibit the mobility of small dislocation loops and SIA clusters. In W-3%Ta (R) irradiated at 0.05 and 0.2 dpa, the coalescence process of the elongated dislocation loops was observed. Solute Ta may inhibit the mobility of SIA clusters. Although no voids and rafts were observed in self-ion irradiated W-3%Re (R) to 0.2 dpa, not only dislocation loops but also voids and rafts were observed in pure W (R) to 0.2 dpa. Solute Re may inhibit the mobility of small dislocation loops and SIA clusters, so that solute Re would suppress the raft formation and then the void formation under self-ion irradiation. The dispersed barrier model was applied to the irradiation hardening of the proton-irradiated W-3%Re (R) up to 0.2 dpa before developing dislocation lines. The hardening in the proton-irradiated W-3%Re (R) up to 0.2 dpa is mainly due to TEM-visible voids and dislocation loops.
We studied the effects of radiofrequency electromagnetic fields (RF-EMFs) exposure on neuronal functions of mice. Particularly, we focused on RF-EMF effects on synaptic vesicles (SVs), which store ...neurotransmitters at axon terminals or synaptic boutons. C57 BL/6 mice were exposed to 835 MHz RF-EMF (4.0 W/kg SAR, for 5 h daily) and alterations in SVs at presynaptic terminals in the cerebral cortex were determined. Ultrastructure of randomly selected cortical neurons was observed using typical electron microscopy and bio-high voltage electron microscopy (Bio-HVEM) methods, which enable the estimation of the numbers and size of SVs. The density of the SVs (number /10 μm2 or 40 μm3) was significantly decreased in the presynaptic boutons of cortical neurons after RF-EMF exposure. Furthermore, qPCR and immunoblotting analyses revealed that the expression of synapsins I/II (Syns I/II) genes and proteins were significantly decreased in the cortical neurons of RF-EMF exposed mice. The present study suggested that alteration of SVs and Syn levels may result in alterations of neurotransmitters in the cerebral cortex following RF-EMF exposure.
To evaluate the utility of immediate post-procedure computed tomography (IPP-CT) and routine one-hour chest radiography (1HR-CXR) for detecting and managing pneumothorax in patients undergoing ...computed tomography (CT)-guided percutaneous lung biopsy.
All CT-guided percutaneous lung biopsies performed between May 2014 and August 2021 at a single institution were included. Data from 275 procedures performed on 267 patients (147 men; mean age: 63.5 ± 14.1 years; range 18-91 years) who underwent routine 1HR-CXR were reviewed. Incidences of pneumothorax and procedure-related complications on IPP-CT and 1HR-CXR were recorded. Associated variables, including tract embolization methods, needle diameter/type, access site, lesion size, needle tract distance, and number of biopsy samples obtained were analyzed and compared between groups with and without pneumothorax.
Post-procedure complications included pneumothorax (30.9%, 85/275) and hemoptysis (0.7%, 2/275). Pneumothorax was detected on IPP-CT and 1HR-CXR in 89.4% (76/85) and 100% (85/85), respectively. A chest tube was placed in 4% (11/275) of the cases. In 3.3% (9/275) of the cases, delayed pneumothorax was detected only on 1HR-CXR, but no patient in this group necessitated chest tube placement. The incidence of pneumothorax was not significantly different between tract embolization methods (p = 0.36), needle diameters (p = 0.36) and types (p = 0.33), access sites (p = 0.07), and lesion sizes (p = 0.88). On logistic regression, a lower biopsy sample number (OR = 0.49) was a protective factor, but a longer needle tract distance (OR = 1.16) was a significant risk factor for pneumothorax.
Following CT-guided percutaneous lung biopsy, pneumothorax detected on IPP-CT strongly indicates persistent pneumothorax on 1HR-CXR and possible chest tube placement. If no pneumothorax is identified on IPP-CT, follow-up 1HR-CXR may be required only for those who develop symptoms of pneumothorax.
Chemical aspects of the ignition of a primary reference fuel (PRF)/air mixture under reactivity controlled compression ignition (RCCI) and stratified charge compression ignition (SCCI) conditions are ...investigated by analyzing two-dimensional direct numerical simulation (DNS) data with chemical explosive mode (CEM) analysis. CEMA is adopted to provide fundamental insights into the ignition process by identifying controlling species and elementary reactions at different locations and times. It is found that at the first ignition delay, low-temperature chemistry (LTC) represented by the isomerization of alkylperoxy radical, chain branching reactions of keto-hydroperoxide, and H-atom abstraction of n-heptane is predominant for both RCCI and SCCI combustion. In addition, explosion index and participation index analyses together with conditional means on temperature verify that low-temperature heat release (LTHR) from local mixtures with relatively-high n-heptane concentration occurs more intensively in RCCI combustion than in SCCI combustion, which ultimately advances the overall RCCI combustion and distributes its heat release rate over time. It is also found that at the onset of the main combustion, high-temperature heat release (HTHR) occurs primarily in thin deflagrations where temperature, CO, and OH are found to be the most important species for the combustion. The conversion reaction of CO to CO2 and hydrogen chemistry are identified as important reactions for HTHR. The overall RCCI/SCCI combustion can be understood by mapping the variation of 2-D RCCI/SCCI combustion in temperature space onto the temporal evolution of 0-D ignition.
Two sediment cores from the Chukchi Sea margin were investigated for the Arctic sea-ice biomarker IP25, along with marine and terrestrial sterols and glycerol dialkyl glycerol tetraethers (GDGTs). ...This is the first paleoclimatic application of IP25 in the Chukchi-Alaskan region of the Arctic, which is key for understanding Arctic–Pacific interactions and is experiencing rapid sea-ice retreat under present warming. Sea-ice and related circulation conditions were characterized in this study with a multicentury resolution for the long-term Holocene record to multidecadal for the last several centuries. Sea ice was found to be present during the entire record but with considerable spatial and temporal variability. After very low deglacial IP25 values, possibly related to permanent sea ice and/or an iceberg-dominated environment, cores from the upper slope and shelf show IP25 maxima, interpreted as representing a relative proximity to the sea-ice margin, in the early (ca. 8–9 ka) and middle (ca. 5–6 ka) Holocene, respectively. Along with isoprenoid GDGT distribution, this asynchronicity in sea-ice history probably reflects oceanographic evolution of the Chukchi margin affected by the Beaufort Gyre circulation and Pacific water inflow via Bering Strait. Data for the last several centuries, with elevated values of brassicasterol and terrestrial sterols covarying with dinosterol and IP25, are interpreted in terms of long-distance import by currents combined with diagenetic transformations. We infer that high-amplitude variability in the late ‘Little Ice Age’, starting in the late 18th century, is related to the intensity of the Alaskan Coastal Current. This interval is preceded by three centuries of presumably diminished Alaskan Coastal Current but overall increased Bering Strait Inflow resulting in reduced sea-ice cover according to dinocyst-based data.
Branched glycerol dialkyl glycerol tetraether (brGDGT) is a ubiquitous biomarker in peat and soil used widely to reconstruct terrestrial paleoclimate change. On the other hand, it has rarely been ...reported in paleoclimatic studies on the Korean Peninsula. The present study analyzed the brGDGT of core sediments (ES14-GC02) collected from the Hupo Trough (southwestern East Sea) to test whether the brGDGT proxies reflect the terrestrial environmental conditions of East Asia including the Korean Peninsula. At the core-top sediments, the brGDGT-derived mean annual air temperature (MAAT,
ca.
13.7 °C) concurred with the modern annual mean of measured atmospheric temperature (
ca.
13.3 °C). Core ES14-GC02 is characterized by two lithologic units: a high MAAT and pH in the upper Unit A and a low MAAT and pH in the lower Unit B. In particular, a bi-plot of CBT (cyclization ratio of branched tetraethers) and MBT′ (methylation index of branched tetraethers) shows the distinct difference between the last glacial maximum (LGM) and the Holocene. These results indicate that the sources of brGDGT in the Hupo Trough are complex (in situ production, terrestrial source, and unknown source). Thus, great care should be taken when interpreting the absolute value of MAAT in the Hupo Trough. Nevertheless, despite this caveat, the downcore variation of the brGDGT proxies reflects changes in the terrestrial environment in the Korean Peninsula since the LGM. This study suggests that branched GDGTs of neritic marine sediments can be used to improve terrestrial paleoclimatic studies on the Korean Peninsula.
We investigated Quaternary benthic foraminifera in core GPC1803 in the eastern equatorial Indian Ocean since ~740 ka to examine the relationship between benthic foraminiferal fauna and ballasting of ...particulate organic matter (POM) by calcareous plankton skeletons. Because plankton skeletons affect POM sinking in the water column as ballasts, ballasting of POM by biominerals may play an important role to linkage between the surface and deep-sea paleoceanography. We consider this scheme, based on faunal analysis of benthic foraminifera. From multidimensional scaling (MDS) of fossil benthic foraminifera, we recognized two MDS axes. Based on the scores of MDS axis 1, we subdivided our study period into five intervals and identified two major faunal transitions at ~370 ka and ~ 210 ka. After ~210 ka, the food supply to the seafloor increased with an increase in the past flux of calcareous plankton skeletons. A positive correlation between the benthic foraminifera accumulation rate and the carbonate mass accumulation rate existed during ~600–370 ka and after ~210 ka. It is reasonable to suppose that the increase in calcareous plankton skeletons stimulated more efficient vertical transport of POM through the water column due to the positive ballasting effect on POM. The ~370–210 ka period seemed to represent a transitional phase in food supply. Prior to ~370 ka, alternations among three seasonal food supply-related species were generally observed along with glacial–interglacial variations probably under lower food supply, compared with the after ~210 ka period; however, alternations among these three species became obscure and intermittent after ~370 ka. The nearly continuous common occurrences of these seasonal food supply-related species before ~370 ka might have been enhanced by a lower past flux of calcareous plankton skeletons. Scenario of ballasting of POM by biomineral might explain long-term changes of carbonate corrosivity in the Indian Ocean, similarly in the Atlantic and eastern equatorial Pacific Oceans, during the mid-Brunhes dissolution interval.
•Quaternary deep-sea benthic foraminifera in the equatorial Indian Ocean•Positive relationship between BFAR and carbonate MAR after ~210 ka•Common occurrences of seasonal food supply-related species before ~370 ka•Changes in the influence of ballasting of POM by calcareous plankton
PDF
