Near-infrared responsive gold nanorods for highly sensitive colorimetric and photothermal lateral flow immuno-detection of SARS-CoV-2.

The highly infectious characteristics of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlight the necessity of sensitive and rapid nucleocapsid (N) protein-based antigen testing for early triage and epidemic management. In this study, a colorimetric and photothermal dual-mode lateral flow immunoassay (LFIA) platform for the rapid and sensitive detection of the SARS-CoV-2 N protein was developed based on gold nanorods (GNRs), which possessed tunable local surface plasma resonance (LSPR) absorption peaks from UV-visible to near-infrared (NIR). The LSPR peak was adjusted to match the NIR emission laser 808 nm by controlling the length-to-diameter ratio, which could maximize the photothermal conversion efficiency and achieve photothermal detection signal amplification. Qualitative detection of SARS-CoV-2 N protein was achieved by observing the strip color, and the limit of detection was 2 ng mL-1, while that for photothermal detection was 0.096 ng mL-1. Artificial saliva samples spiked with the N protein were analyzed with the recoveries ranging from 84.38% to 107.72%. The intra-assay and inter-assay coefficients of variation were 6.76% and 10.39%, respectively. We further evaluated the reliability of this platform by detecting 40 clinical samples collected from nasal swabs, and the results matched well with that of nucleic acid detection (87.5%). This method shows great promise in early disease diagnosis and screening.

A non-residue surface modification strategy for active-targeting fluorescent silica nanoparticles to cellular organelles.

Silica nanoparticles (SiNPs) with a chemically modified surface typically have a complicated chemical composition, which can significantly differ from their intended design. In this study, we systematically studied the effects of two surface modification methods on active-targeting of intracellular organelles of SiNPs: (1) the widely used step-by-step approach, which involves modifying SiNPs in two steps, i.e., the outer surface of SiNPs was firstly modified with amino groups and then these amino groups were linked with targeting groups, and (2) a newly developed one-step approach in which the ligand-silane complex is initially synthesized, followed by chemically immobilizing the complex on the surface of SiNPs. In the one-step approach, the molar ratio of reactants was precisely tuned so that there are no reactive groups left on the outer surface of SiNPs. Two essential organelles, mitochondria and the nucleus, were selected to compare the targeting performances of SiNPs synthesized via these two approaches. By characterizing physicochemical properties, including structural properties, the number of amino groups, surface charge, polydispersity, and cell colocalization, we demonstrated that SiNPs synthesized via the one-step approach with no residual linkage groups on their surface showed significantly improved mitochondria- and nucleus-targeting performances. This precise control of surface properties allows for optimized biological behavior and active-targeting efficiency of SiNPs. We anticipate that such simple and efficient synthetic strategies will enable the synthesis of effective SiNPs for active-targeting organelles in various biological applications.

Direct Bilirubin, but not Indirect Bilirubin, is Associated with Short-term Adverse Events in HFpEF.

OBJECTIVE: Abnormal live function tests have been identified as independent risk factors for ominous prognosis in patients with heart failure. However, most of the previous studies have failed to determine the contribution of direct bilirubin (DBIL) and indirect bilirubin (IBIL) separately. Hence, we aimed to explore whether DBIL or IBIL is correlated with the prognosis of heart failure with preserved ejection fraction (HFpEF). METHODS: A total of 19837 patients were hospitalized for HFpEF between January 2012 and January 2022 in Fuqing City Hospital affiliated with Fujian Medical University. The primary endpoint was in-hospital all-cause mortality. Secondary endpoints included in-hospital cardiovascular mortality and 30-day re-admission for heart failure. RESULTS: Univariable analysis indicated that patients with elevated DBIL or IBIL were exposed to a higher risk of mortality and re-admission. However, in multivariable models, both ln-transformed DBIL and TBIL, but not IBIL, were independent risk factors for in-hospital all-cause mortality (hazard ratio (HR)=1.796, 95% confidential interval (CI)=1.477-2.183, P<0.001; HR=1.854, 95% CI=1.461-2.352, P.0.001; HR=1.161, 95% CI=0.959-1.407, P=0.126) and in-hospital cardiovascular mortality (HR=1.831, 95% CI=1.345-2.492, P.0.001; HR=1.899, 95% CI=1.300-2.773, P=0.001; HR=1.145, 95% CI=0.841-1.561, P=0.389). Only DBIL remained independently associated with 30-day readmission for heart failure (HR=1.361, 95% CI=1.036-1.787, P=0.027). Adding ln-transformed DBIL to model 1 increased its discriminatory capacity (C-statistic: 0.851 to 0.869, respectively), whereas adding ln-transformed IBIL yielded little increment (C-statistic: 0.851 to 0.852, respectively). CONCLUSION: DBIL, but not IBIL, was associated with short-term ominous prognosis in patients with HFpEF. Hence, DBIL may be the superior predictor for prognosis in HFpEF.

Green synthesis of highly stable CsPbBr3 perovskite nanocrystals using natural deep eutectic solvents as solvents and surface ligands.

Perovskite nanocrystals (PNCs) have attracted widespread attention as promising materials for the optoelectronic field due to their remarkable photophysical properties and structural tunability. However, their poor stability and the use of toxic organic solvents in the preparation process have severely restricted their practical applications. Herein, a facile, rapid and toxic organic solvent-free synthesis strategy of CsPbBr3 PNCs was developed for the first time via the ligand-assisted reprecipitation (LARP) method using natural deep eutectic solvents (NADESs) as solvents and surface ligands. In this method, the NADESs not only functioned as solvents for green synthesis, but also served simultaneously as surface ligands of CsPbBr3 PNCs to significantly improve their optical properties and stability. The as-synthesized CsPbBr3 PNCs exhibited high photoluminescence quantum yield (PLQY, ∼96.8%), narrow full width at half-maximum (FWHM, ∼18.8 nm) and a high stability that retained 82.9% of PL intensity after 70 days. This work provides a new strategy for the green synthesis of PNCs, which promises feasibility for the industrial large-scale synthesis of high-quality PNCs.

The efficacy and safety of Sacubitril/Valsartan in the treatment of chronic heart failure: a meta-analysis.

OBJECTIVE: A meta-analysis of the studies involving Sacubitril/Valsartan in chronic heart failure was performed to compare the efficacy and safety of Sacubitril/Valsartan with traditional drug therapy in chronic heart failure. METHODS: We searched databases from PubMed, EMBASE, the Cochrane Library, Web of Science, and clinicaltrials.gov for studies published between 2010 and 2020 that reported efficacy and safety following Sacubitril/Valsartan administration. RESULTS: Ten studies enrolling 1689 patients were included. Sacubitril/Valsartan outperformed traditional medicine (especially the Non-ARNI group) in terms of blood pressure, biomarkers and cardiac reverse remodeling indices, with striking changes in left ventricular ejection fraction, systolic blood pressure. Sacubitril/Valsartan showed significant benefit in renal function in patients with chronic heart failure. CONCLUSIONS: Compared with traditional drugs, Sacubitril/Valsartan significantly improved echocardiography, vital signs and biomarkers of patients with chronic heart failure, and reduced the incidence of hyperkalemia, renal dysfunction and other adverse reactions. Further large sample trials are needed in the future to determine the long-term effects of Sacubitril/Valsartan on efficacy and safety in patients with chronic heart failure.

Retinoid X receptor agonists attenuates cardiomyopathy in streptozotocin-induced type 1 diabetes through LKB1-dependent anti-fibrosis effects.

Diabetic cardiac fibrosis increases ventricular stiffness and facilitates the occurrence of diastolic dysfunction. Retinoid X receptor (RXR) plays an important role in cardiac development and has been implicated in cardiovascular diseases. In the present study, we investigated the effects of RXR agonist treatment on streptozotocin (STZ)-induced diabetic cardiomyopathy (DCM) and the underlying mechanism. Sprague-Dawley (SD) rats induced by STZ injection were treated with either RXR agonist bexarotene (Bex) or vehicle alone. Echocardiography was performed to determine cardiac structure and function. Cardiac fibroblasts (CFs) were treated with high glucose (HG) with or without the indicated concentration of Bex or the RXR ligand 9-cis-retinoic acid (9-cis-RA). The protein abundance levels were measured along with collagen, body weight (BW), blood biochemical indexes and transforming growth factor-ß (TGF-ß) levels. The effects of RXRα down-regulation by RXRα small interfering RNA (siRNA) were examined. The results showed that bexarotene treatment resulted in amelioration of left ventricular dysfunction by inhibiting cardiomyocyte apoptosis and myocardial fibrosis. Immunoblot with heart tissue homogenates from diabetic rats revealed that bexarotene activated liver kinase B1 (LKB1) signaling and inhibited p70 ribosomal protein S6 kinase (p70S6K). The increased collagen levels in the heart tissues of DCM rats were reduced by bexarotene treatment. Treatment of CFs with HG resulted in significantly reduced LKB1 activity and increased p70S6K activity. RXRα mediated the antagonism of 9-cis-RA on HG-induced LKB1/p70S6K activation changes in vitro. Our findings suggest that RXR agonist ameliorates STZ-induced DCM by inhibiting myocardial fibrosis via modulation of the LKB1/p70S6K signaling pathway. RXR agonists may serve as novel therapeutic agents for the treatment of DCM.

Developments in the study of gastrointestinal microbiome disorders affected by FGF19 in the occurrence and development of colorectal neoplasms.

Colorectal neoplasms are a type of malignant digestive system tumor that has become the third-highest morbidity tumor in China and the fourth leading cause of cancer-related death worldwide. The role of the gastrointestinal (GI) microbiome in bile acid metabolism, inflammation, and insulin resistance and its strong correlation with the occurrence and development of colorectal neoplasms have gradually led to it becoming a target area of tumor research. Fibroblast growth factor (FGF) 19 is a hormone that is secreted in mainly the ileum and can regulate bile acid biosynthesis, improve inflammation, and regulate insulin resistance. The relationship of the GI microbiome, FGF19 and its carcinogenic activities in colorectal neoplasms enticed us to search for potential targets and research ideas for the clinical diagnosis and treatment of colorectal neoplasms.