Effect of amubarvimab-romlusevimab for treatment of severe COVID-19 in intensive care units: A retrospective cohort study.

Amubarvimab-romlusevimab is a commonly recommended antiviral treatment in China for adult patients with mild or moderate SARS-CoV-2 infections, especially for patients with a high risk factor for progression to severe COVID-19. However, its exact efficacy in patients with severe Covid-19 is not yet known.This is a single-center retrospective cohort study, in which we collected the general data, laboratory tests, radiological characteristics, viral conversion status, and prognosis of the disease from patients with COVID-19 hospitalized, from December 2022 to March 2023 in the Department of Critical Care Medicine. The amubarvimab-romlusevimab therapy can reduce the 28-day mortality (29.79 % vs 51.35 %, p = 0.02), and ICU mortality (29.79 % vs 55.41 %, p = 0.006) of severe COVID-19.A 1:1 PSM (Propensity Score Matching) was performed to reduce bias, in order to ensure the two groups were balanced and comparable. In the matched population (n = 47), there were no statistically significant differences between the mAbs (monoclonal antibody)group and the Non-antiviral group in 28-day, and thromboembolic events in COVID-19 patients. The 40-day survival analysis shows that mAbs therapy can improve patient prognosis (HR = 0.45, 95%CI = 0.26-0.76, p = 0.008). However, no significant intergroup difference in the 40-day cumulative viral conversion rate. In a univariate Cox regression analysis, The Amubarvimab - romlusevimab therapy(HR:0.464; CI:[0.252-0.853]; p:0.013) is a protective factor and CRP, PCT, PLT, Lactate, PT, PT-INR, and pt% level at admission were risk factors for clinical prognosis. After including the above covariates, Multifactorial COX regression shows that the Amubarvimab - romlusevimab therapy(HR:0.392; CI:[0.211-0.729]; p:0.003), CRP, Lactate and PT-INR at admission are independent factors for mortality of severe COVID-19. Based on the current data, we conclude that amubarvimab-romlusevimab therapy is beneficial for patients with severe COVID-19.

EGCG suppressed activation of hepatic stellate cells by regulating the PLCE1/IP3/Ca2+ pathway.

(-)-Epigallocatechin-3-O-gallate (EGCG), one of the green tea catechins, exhibits significant antioxidant properties that play an essential role in various diseases. However, the functional role and underlying mechanism of EGCG in stimulating of hepatic stellate cells (HSCs) remain unexplored in transcriptomics sequencing studies. The present study suggests that oral administration of EGCG at a dosage of 200 mg/kg/day for a duration of four weeks exhibits significant therapeutic potential in a murine model of liver fibrosis induced by CCl4. The activation of HSCs in vitro was dose-dependently inhibited by EGCG. The sequencing analysis data reveled that EGCG exerted a regulatory effect on the calcium signal in mouse HSCs, resulting in a decrease in calcium ion concentration. Further analysis revealed that EGCG inhibited the expression of phospholipase C epsilon-1 (PLCE1) and inositol 1, 4, 5-trisphosphate (IP3) in activated mouse HSCs. Additionally, EGCG contributes to the reduction the concentration of calcium ions by regulating PLCE1. After the knockdown of PLCE1, free calcium ion concentrations decreased, resulting in the inhibition of both cell proliferation and migration. Interestingly, the expression of PLCE1 and cytosolic calcium levels were regulated by reactive oxygen species(ROS). Furthermore, our findings suggest that ROS might inhibit the expression of PLCE1 by inhibiting TFEB, a transcription activator involved in the nuclear translocation process. Our study provided novel evidence regarding the regulatory effects of EGCG on activated HSCs (aHSCs) in mice by the calcium signaling pathway, emphasizing the crucial role of PLCE1 within the calcium signaling network of HSCs. The proposition was also made that PLCE1 holds promise as a novel therapeutic target for murine liver fibrosis.

Customized Lanthanide Nanobiohybrids for Noninvasive Precise Phototheranostics of Pulmonary Biofilm Infection.

A noninvasive strategy for in situ diagnosis and precise treatment of bacterial biofilm infections is highly anticipated but still a great challenge. Currently, no in vivo biofilm-targeted theranostic agent is available. Herein, we fabricated intelligent theranostic alginate lyase (Aly)-NaNdF4 nanohybrids with a 220 nm sunflower-like structure (NaNdF4@DMS-Aly) through an enrichment-encapsulating strategy, which exhibited excellent photothermal conversion efficiency and the second near-infrared (NIR-II) luminescence. Benefiting from the site-specific targeting and biofilm-responsive Aly release from NaNdF4@DMS-Aly, we not only enabled noninvasive diagnosis but also realized Aly-photothermal synergistic therapy and real-time evaluation of therapeutic effect in mice models with Pseudomonas aeruginosa biofilm-induced pulmonary infection. Furthermore, such nanobiohybrids with a sheddable siliceous shell are capable of delaying the NaNdF4 dissolution and biodegradation upon accomplishing the therapy, which is highly beneficial for the biosafety of theranostic agents.

Optimizing cell voltage dependence on size of carbon nanotube-based electrodes in Na-ion and K-ion batteries.

Sodium-ion batteries (NIBs) and potassium-ion batteries (KIBs) are gaining extensive attention as promising alternatives to lithium-ion batteries owing to their superior energy density and cost-effectiveness. However, the larger ionic radius of Na+ and K+ ions in comparison to Li+ ions poses a challenge in designing anode materials characterized by enduring structures and elevated voltage to facilitate the efficacy of high-performance NIBs and KIBs. Carbon nanomaterials, particularly carbon nanotubes (CNTs), have emerged as a potential candidate in anode materials. Herein, we used density functional theory calculations to study the cell voltage of CNTs in relation to Na-ion and K-ion storage as a function of CNT size. The adsorption energy profiles of both Na+@CNT and K+@CNT systems exhibit a descending trend concomitant with the increase in the CNT diameter, where Na+/K+ ion primarily prefers to adsorb in the interior wall of CNT. Conversely, the cell voltage for the Na and K system gradually increases with the increasing diameter of CNT, which can be attributed to the stronger electrostatic interaction validated by energy decomposition calculation. The voltage of Na-ion adsorbed on the inter wall of (10,10) CNT attains 1.29 V, close to the previously theoretical voltage of Li-ion on the same CNT (1.35 V), while the much lower voltage pertaining to K-ion adsorption on the inter wall of (10,10) CNT just stands at 0.59 V, suggesting the viability of CNT-based electrode for NIBs but not for KIBs. These findings lay a solid foundation for delineating the interrelationship between the voltage properties of CNT as prospective anode material and their structural characteristics, thereby expanding the application of CNT-based optoelectronic devices.

Autophagic degradation of MVBs in LSECs promotes Aldosterone induced-HSCs activation.

BACKGROUND AND AIMS: The important role of extracellular vesicles (EVs) in liver fibrosis has been confirmed. However, EVs derived from liver sinusoidal endothelial cells (LSECs) in the activation of hepatic stellate cells (HSCs) and liver fibrosis is still unclear. Our previous work demonstrated that Aldosterone (Aldo) may have the potential to regulate EVs from LSECs via autophagy pathway. Thus, we aim to investigate the role of Aldo in the regulation of EVs derived from LSECs. APPROACH AND RESULTS: Using an Aldo-continuous pumping rat model, we observed that Aldo-induced liver fibrosis and capillarization of LSECs. In vitro, transmission electron microscopy (TEM) revealed that stimulation of Aldo led to the upregulation of autophagy and degradation of multivesicular bodies (MVBs) in LSECs. Mechanistically, Aldo upregulated ATP6V0A2, which promoted lysosomal acidification and subsequent autophagy in LSECs. Inhibiting autophagy with si-ATG5 adeno-associated virus (AAV) in LSECs effectively mitigated Aldo-induced liver fibrosis in rats. RNA sequencing and nanoparticle tracking (NTA) analyses of EVs derived from LSECs indicated that Aldo result in a decrease in both the quantity and quality of EVs. We also observed a reduction in the protective miRNA-342-5P in EVs derived from Aldo-treated LSECs, which may play a critical role in HSCs activation. Target knockdown of EV secretion with si-RAB27a AAV in LSECs led to the development of liver fibrosis and HSC activation in rats. CONCLUSION: Aldo-induced Autophagic degradation of MVBs in LSECs promotes a decrease in the quantity and quality of EVs derived from LSECs, resulting in the activation of HSCs and liver fibrosis under hyperaldosteronism. Modulating the autophagy level of LSECs and their EV secretion may represent a promising therapeutic approach for treating liver fibrosis.

Using a cyclocarbon additive as a cyclone separator to achieve fast lithiation and delithiation without dendrite growth in lithium-ion batteries.

Carbon materials are widely used for reversible lithium uptake in the anode of lithium-ion batteries. Nevertheless, the challenge of uncontrollable dendrite deposition during fast charge-discharge cycles remains a grand hurdle. Various strategies have been explored to prevent detrimental heterogeneous dendrite metal deposits, such as interface engineering and electrolyte modification, but they often compromise the reverse diffusion freedom of Li+ ions during discharging and are incompatible with the most mainstream use of graphite as an anode material. Here, we propose the incorporation of a novel carbon allotrope of cyclocarbon as a potential additive in the anode. In contrast to conventional carbon materials, density functional theory calculations reveal that cyclocarbon has a much higher affinity for Li atoms than Li+ ions, even surpassing the inherent cohesion of Li atoms, due to the charge transfer from the 2s orbital of Li atoms to the unique in-plane π orbital of cyclocarbon. Furthermore, ab initio molecular dynamics simulations show that Li+ ions can shuttle freely back and forth across cyclocarbon, whereas the lithiation process for Li atoms occurs rapidly within picoseconds. The delithiation of Li atoms within cyclocarbon follows a voltage-gated mechanism that is effectively controlled by an external electric field of 3 V nm-1. Remarkably, cyclocarbon exhibits potential compatibility with commercialized graphite electrodes via the π-π interaction and also can be extended to sodium-ion and potassium-ion batteries. These distinct compatibility, scalability and electrochemical properties of cyclocarbon provide a new avenue to realize both safety and ultrafast rechargeable performance of ion batteries.

Caveolin-1 depletion attenuates hepatic fibrosis via promoting SQSTM1-mediated PFKL degradation in HSCs.

The key glycolytic enzyme phosphofructokinase (PFK) is responsible for maintaining glycolytic stability and an important energy source for activating hepatic stellate cells (HSCs). However, its regulation in activated HSCs remains unclear. Caveolin-1 (Cav1), a major constituent of caveolae, has emerged as a key target for triggering glycolysis. However, the relationship between Cav1 and glycolysis during HSC activation is not well established. In this study, Cav1 was upregulated in mouse and human fibrotic liver tissues. We concluded that HSC-specific Cav1 knockdown markedly alleviates liver injury and fibrosis. Mechanistically, Cav1 was elevated during primary mouse HSC activation, competing with SQSTM1 for the regulatory subunit of PFK liver type and inhibiting the SQSTM1-mediated autophagy-independent lysosomal degradation pathway to sustain HSC activation. We also identified the heptapeptide alamandine as a promising therapeutic agent that downregulates Cav1 protein levels via proteasomal degradation and may impair glycolysis. Our study provides evidence of the crucial role and mechanism of Cav1 in the glucose metabolic network in HSCs and highlights Cav1 as a critical therapeutic target for the treatment of liver fibrosis.

Sacubitril/valsartan alleviates sepsis-induced acute lung injury via inhibiting GSDMD-dependent macrophage pyroptosis in mice.

Sepsis-induced acute lung injury (ALI) is a life-threatening disorder with intricate pathogenesis. Macrophage pyroptosis reportedly plays a vital role in ALI. Although it has been established that angiotensin receptor blockers (ARBs) can reduce sepsis-induced organ injury, the efficacy of sacubitril/valsartan (SV) for sepsis has been largely understudied. Here, we aimed to investigate the role of SV in sepsis-induced ALI. Caecal ligation and puncture (CLP) were used to induce polymicrobial sepsis and related ALI. The therapeutic effects of SV in CLP mice were subsequently assessed. Gasdermin D (GSDMD)-/- mice were used to validate the signalling pathways affected by SV. In vitro, mouse bone marrow-derived macrophages (BMDMs) and Raw264.7 cells were treated with SV following exposure to lipopolysaccharide and adenosine triphosphate. Finally, the serum obtained from 42 septic patients was used for biochemical analysis. Compared to the other ARBs, SV yielded more pronounced anti-inflammatory effects on macrophages. In vivo, SV decreased mortality rates, significantly reduced lung damage and prevented the inflammatory response in CLP mice. In addition, SV suppressed GSDMD-mediated macrophage pyroptosis in mice. In BMDMs and Raw264.7 cells, the anti-inflammatory and anti-pyroptosis properties of SV were verified. SV treatment effectively inhibited NLRP3 inflammasome activation and prevented macrophage pyroptosis in a GSDMD-dependent manner. Furthermore, we found that septic individuals had considerably higher serum angiotensin II levels. Overall, we found that SV might prevent ALI in CLP mice by inhibiting GSDMD-mediated pyroptosis of macrophages. Thus, SV might be a viable drug for sepsis-induced ALI.

Multistate Circularly Polarized Luminescence Switching through Stimuli-Induced Co-Conformation Regulations of Pyrene-Functionalized Topologically Chiral [2]Catenane.

Aiming at the construction of novel circularly polarized luminescence (CPL) switches with multiple switchable emission states and high dissymmetry factors (glum ), topologically chiral [2]catenanes were employed as the key platform to construct a novel multistate CPL switching system. Taking advantage of the precise co-conformation regulations of the resultant pyrene-functionalized [2]catenanes under different external stimuli, reversible transformations between three emission states with different CPL performances, i.e. the initial "closed" form with a |glum | value of 0.012, the "open" form with an almost complete turn-off of CPL emission, and the "protonated" form with a boosted |glum | value of 0.022, were successfully realized. This study demonstrates the successful construction of not only the first topological chirality-based CPL switch, but also a novel bidirectional CPL switch, thus providing a promising platform for the construction of novel chiral materials.

Two-photon fluorescence imaging and ratiometric quantification of mitochondrial monoamine oxidase-A in neurons.

Herein, we designed and developed a single two-photon ratiometric fluorescence probe (TMF2P) for selective and accurate determination of mitochondrial MAO-A in live neurons. It was discovered that the increases in MAO-A levels under oxidative stress resulted in an elevated influx of Ca2+ flow into mitochondria through the transient receptor potential melastatin 2 (TRPM2) channels.

Enhanced self-activated far-red photoluminescence from Sr3LiSbO6 phosphors by Gd3+ doping for plant growth.

Sr3LiSbO6 phosphors were prepared by high temperature solid state reaction method. The crystal phase, morphology and optical properties were characterized by X-ray powder diffraction spectroscopy, scanning electronic microscope, absorption and photoluminescence (PL) spectra. The XRD Rietveld refinement was performed to obtain the detailed crystal structure of Sr3LiSbO6. The electronic structure was analyzed by density functional theory (DFT) calculation. Sr3LiSbO6 possessed indirect band structure and the band-gap were determined to be 3.17 eV. Self-activated far-red emissions at 630-800 nm were detected under the excitation at 340 nm, which was proposed to originate from the transition between interstitial oxygen defective state to six hybrid 4d105s0 states of Sb5+ according to the results of PL spectra of samples annealed at different atmospheres. The PL intensity can be significantly enhanced by 2.9 times after doping 2 mol% Gd3+ ions in Sr3LiSbO6. The internal quantum efficiency of Sr3LiSbO6:2 mol%Gd3+ was determined to be 25.2%. The influence of the Gd3+ doping on the self-activated PL lifetimes of Sr3LiSbO6 and the thermal quenching property of Sr3LiSbO6:2 mol%Gd3+ was studied.

Zeolitic imidazolate framework-8 reinforced hollow-fiber liquid-phase microextraction of free urinary biomarkers of whole grain intake followed by CE analysis.

The whole grain intake is closely associated with human health. In this work, three-phase dynamic hollow-fiber liquid-phase microextraction reinforced with 0.10 mg/mL 30 nm zeolitic imidazolate framework-8 nanoparticles was introduced for purification and enrichment of free urinary metabolite biomarkers of whole grain intake. Eight milliliters of HCl (pH 3.00) and 8 µL of 300 mM NaOH solutions were used as the donor and acceptor phases, respectively. The temperature and stirring rate were kept at 25℃ and 500 rpm, and the extraction time was 40 min. The extraction process required no further desorption, and the resultant extract was directly used for electrophoretic analysis without derivatization. Based on the synergistic effect of hollow-fiber liquid-phase microextraction and the electrophoretic stacking, the enrichment factors of 3,5-dihydroxybenzoic acid and 3-(3,5-dihydroxyphenyl)-1-propionic acid reached 1018-1034 times, and their limits of detection achieved 0.33-0.67 ng/mL (S/N = 3) in urine matrix. The developed method has been successfully used for urine analysis, and the sample recovery data were in the range of 97.0-103.5%. This developed method provided an attractive alternative for the determination of urinary metabolite biomarkers of whole grain intake due to its sensitive, fast, low-cost, and environmental-friendly features.