Multi-dimensional epidemiology and informatics data on COVID-19 wave at the end of zero COVID policy in China.

Background: China exited strict Zero-COVID policy with a surge in Omicron variant infections in December 2022. Given China's pandemic policy and population immunity, employing Baidu Index (BDI) to analyze the evolving disease landscape and estimate the nationwide pneumonia hospitalizations in the post Zero COVID period, validated by hospital data, holds informative potential for future outbreaks. Methods: Retrospective observational analyses were conducted at the conclusion of the Zero-COVID policy, integrating internet search data alongside offline records. Methodologies employed were multidimensional, encompassing lagged Spearman correlation analysis, growth rate assessments, independent sample T-tests, Granger causality examinations, and Bayesian structural time series (BSTS) models for comprehensive data scrutiny. Results: Various diseases exhibited a notable upsurge in the BDI after the policy change, consistent with the broader trajectory of the COVID-19 pandemic. Robust connections emerged between COVID-19 and diverse health conditions, predominantly impacting the respiratory, circulatory, ophthalmological, and neurological domains. Notably, 34 diseases displayed a relatively high correlation (r > 0.5) with COVID-19. Among these, 12 exhibited a growth rate exceeding 50% post-policy transition, with myocarditis escalating by 1,708% and pneumonia by 1,332%. In these 34 diseases, causal relationships have been confirmed for 23 of them, while 28 garnered validation from hospital-based evidence. Notably, 19 diseases obtained concurrent validation from both Granger causality and hospital-based data. Finally, the BSTS models approximated approximately 4,332,655 inpatients diagnosed with pneumonia nationwide during the 2 months subsequent to the policy relaxation. Conclusion: This investigation elucidated substantial associations between COVID-19 and respiratory, circulatory, ophthalmological, and neurological disorders. The outcomes from comprehensive multi-dimensional cross-over studies notably augmented the robustness of our comprehension of COVID-19's disease spectrum, advocating for the prospective utility of internet-derived data. Our research highlights the potential of Internet behavior in predicting pandemic-related syndromes, emphasizing its importance for public health strategies, resource allocation, and preparedness for future outbreaks.

Clinical features of COVID-19-related optic neuritis: a retrospective study.

Objective: This retrospective study aimed to investigate the clinical features of optic neuritis associated with COVID-19 (COVID-19 ON), comparing them with neuromyelitis optica-associated optic neuritis (NMO-ON), myelin oligodendrocyte glycoprotein-associated optic neuritis (MOG-ON), and antibody-negative optic neuritis (antibody-negative ON). Methods: Data from 117 patients (145 eyes) with optic neuritis at the Shantou International Eye Center (March 2020-June 2023) were categorized into four groups based on etiology: Group 1 (neuromyelitis optica-related optic neuritis, NMO-ON), Group 2 (myelin oligodendrocyte glycoprotein optic neuritis, MOG-ON), Group 3 (antibody-negative optic neuritis, antibody-negative ON), and Group 4 (optic neuritis associated with COVID-19, COVID-19 ON). Characteristics of T2 and enhancement in orbital magnetic resonance imaging (MRI) were assessed. Best-corrected visual acuity (BCVA) was compared before treatment, at a short-term follow-up (14 days), and at the last follow-up after treatment. Results: The COVID-19-associated optic neuritis (COVID-19 ON) group exhibited 100% bilateral involvement, significantly surpassing other groups (P < 0.001). Optic disk edema was observed in 100% of COVID-19 ON cases, markedly differing from neuromyelitis optica-related optic neuritis (NMO-ON) (P = 0.023). Orbital magnetic resonance imaging (MRI) revealed distinctive long-segment lesions without intracranial involvement in T1-enhanced sequences for the COVID-19 ON group compared to the other three groups (P < 0.001). Discrepancies in optic nerve sheath involvement were noted between the COVID-19 ON group and both NMO-ON and antibody-negative optic neuritis (antibody-negative ON) groups (P = 0.028). Before treatment, no significant difference in best-corrected visual acuity (BCVA) existed between the COVID-19 ON group and other groups. At the 14-day follow-up, BCVA in the COVID-19 ON group outperformed the NMO-ON (P < 0.001) and antibody-negative ON (P = 0.028) groups, with no significant difference observed compared to the myelin oligodendrocyte glycoprotein optic neuritis (MOG-ON) group. At the last follow-up after treatment, BCVA in the COVID-19 ON group significantly differed from the NMO-ON group (P < 0.001). Conclusion: Optic neuritis associated with COVID-19 (COVID-19 ON) predominantly presents with bilateral onset and optic disk edema. Orbital magnetic resonance imaging (MRI) demonstrates that COVID-19 ON presents as long-segment enhancement without the involvement of the intracranial segment of the optic nerve in T1-enhanced images. Glucocorticoid therapy showed positive outcomes.

Y-shaped DNA-Mediated hybrid nanoflowers as efficient gene carriers for fluorescence imaging of tumor-related mRNA in living cells.

Organic-inorganic hybrid nanomaterial has gained much attention due to its excellent performances in bioanalysis and biomedicine. However, the preparation of DNA-inorganic hybrid nanomaterial with suitable size for cell uptake remains a huge challenge. Herein, a moderate biomineralization strategy for synthesis of Y-DNA@Cu3(PO4)2 (Y-DNA@CuP) hybrid nanoflowers is reported. Y-DNA with a loop structure is used as both the biomineralization template and the recognition unit for thymidine kinase 1 (TK1) mRNA. The Y-DNA probe can linearly response to TK1 mRNA target sequence in a range from 2 nM to 150 nM with the limit of detection as low as 0.56 nM. Interestingly, the presence of Y-DNA significantly decreases the size of Cu3(PO4)2 (CuP) particles, which allows them suitable for intracellular applications as gene nanocarriers. Once inside the cells, the hybrid nanoflowers dissolve and release the Y-DNA probes. Then, the intracellular TK1 mRNA hybridizes with the loop region of Y-DNA, which dissociates the Cy3-labeled loop strand and turns on the red fluorescence. Through the real-time imaging of the intracellular TK1 mRNA, the assessment of tumor cells before and after the treatment of drugs including ß-estradiol and tamoxifen is achieved.

MoS2 quantum dots modified with a labeled molecular beacon as a ratiometric fluorescent gene probe for FRET based detection and imaging of microRNA.

A dual-channel ratiometric nanoprobe is described for detection and imaging of microRNA. It was prepared from MoS2 quantum dots (QDs; with blue emission and excitation/emission peaks at 310/398 nm) which acts as both the gene carrier and as a donor in fluorescence resonance energy transfer (FRET). Molecular beacons containing loops for molecular recognition of microRNA and labeled with carboxyfluorescein (FAM) were covalently attached to the MoS2 QDs and serve as the FRET acceptor. In the absence of microRNA, the nanoprobe exhibits low FRET efficiency due to the close distance between the FAM tag and the QDs. Hybridization with microRNA enlarges the distance between QD and beacon. This results in an enhancement of the FRET efficiency of the nanoprobe. The ratio of green and blue fluorescence (I520/I398) increases linearly in the 5 to 150 nM microRNA concentration range in both aqueous solution and diluted artificial cerebrospinal fluid. The limit of detection (LOD) is as low as 0.38 nM and 0.52 nM, respectively. Other features of this nanoprobe include (a) excellent resistance to nuclease-induced false positive signals and (b) the option to use it for distinguishing different cell lines by in-situ imaging of intracellular microRNAs. Graphical abstract Schematic of a dual-channel photoluminescence nanoprobe for the determination of microRNA-21 (miR-21) by monitoring the microRNA-triggered enhancement of the fluorescence resonance energy transfer (FRET) efficiency between MoS2 QDs and carboxyfluorescein-labeled molecular beacons.

Visual and Colorimetric High-Throughput Analysis of Chiral Carboxylic Acids Based on Enantioselective Charge Shielding of Gold Nanoparticles.

Because chiral carboxylic acids (CCAs) are a class of important biological molecules and common functional moieties found in pharmaceutical molecules, the chiral analysis of CCAs has received much attention. Herein, we developed a simple, rapid, and cost-effective method for visual and colorimetric high-throughput analysis of CCAs using chiral di-imine structure-modified gold nanoparticles (C-AuNPs) as the probe. The C-AuNPs are positively charged in the presence of zinc ion, and they can be enantioselectively shielded by the negatively charged CCA enantiomers. Therefore, upon the addition of different concentrations and enantiomeric excess (ee) of CCAs, the C-AuNP-based sensor shows the different levels of aggregation along with the visual changes in solution color, which can achieve simultaneous analysis of the concentration and ee of CCAs. The chiral recognition mechanism based on C-AuNPs was investigated by the determination of binding constants ( K) and molecular simulation methods. Our approach is expected to have the wide-ranging applications in the developing region for enantio-sensing of various chiral drugs and biomolecules.

A Chiral Sensor Array for Peptidoglycan Biosynthesis Monitoring Based on MoS2 Nanosheet-Supported Host-Guest Recognitions.

Monitoring the dynamic change with respect to chirality and species of amino acids in bacterial peptidoglycan (PG) during cell wall biosynthesis is correlated with bacterial taxonomy, physiology, micropathology, and antibacterial mechanisms. However, this is challenging because reported methods usually lack the ability of chiral analysis with the coexistence of d- and l-amino acids in PG. Here we report a chiral sensor array for PG biosynthesis monitoring through chiral amino acid recognition. Multitypes of host molecule modified MoS2 nanosheets (MNSs) were used as receptor units to achieve more accurate and specific sensing. By applying indicator displacement strategy, the distinct and reproducible fluorescence-response patterns were obtained for linear discriminant analysis (LDA) to accurately discriminate achiral Gly, 19 l-amino acids and the corresponding 19 d-enantiomers simultaneously. The sensor array has also been used for identifying bacterial species and tracking the subtle change of amino acid composition of PG including chirality and species during biosynthesis in different growth status and exogenous d-amino acid stimulation.

Ratiometric optical sensor for high-resolution imaging of pH with low cross-talk.

We synthesize lipophilic, highly efficient, and pH-insensitive oleic acid-modified quantum dots (QDs) with maximum emission at a wavelength of 628 nm. The pH sensing film is fabricated by encapsulating 5-hexadecanoylamino-fluorescein and QDs as the reference in D4-hydromed and plasticized polystyrene. Using a light-emitting diode with a central wavelength of 410 nm as an excitation source, it is shown that the emission wavelengths of the pH sensitive indicator and reference dye have no spectral overlap and match respectively the channels of a 3CCD (RGB) camera with low cross-talk. A series of validation experiments shows that this ratiometric pH optode has good properties of high sensitivity, long-term stability, and photostability. It had a fast response time of <20 s when going from pH 6.3 to pH 8.0. The pH images suggest that the proposed ratiometric pH-sensing approach has great advantage and promise for field applications.

Design and Fabrication of a Ratiometric Planar Optode for Simultaneous Imaging of pH and Oxygen.

This paper presents a simple, high resolution imaging approach utilizing ratiometric planar optode for simultaneous measurement of dissolved oxygen (DO) and pH. The planar optode comprises a plastic optical film coated with oxygen indicator Platinum(II) octaethylporphyrin (PtOEP) and reference quantum dots (QDs) embedded in polystyrene (PS), pH indicator 5-Hexadecanoylamino-fluorescein (5-Fluorescein) embedded in Hydromed D4 matrix. The indicator and reference dyes are excited by utilizing an LED (Light Emitting Diode) source with a central wavelength of 405 nm, the emission respectively matches the different channels (red, green, and blue) of a 3CCD camera after eliminating the excitation source by utilizing the color filter. The result shows that there is low cross-sensitivity between the two analytes dissolved oxygen and pH, and it shows good performance in the dynamic response ranges of 0-12 mg/L and a dynamic range of pH 6-8. The optode has been tested with regard to the response times, accuracy, photostability and stability. The applied experiment for detecting pH/Oxygen of sea-water under the influence of the rain drops is demonstrated. It is shown that the planar optode measuring system provides a simple method with low cross-talk for pH/Oxygen imaging in aqueous applications.

Ratiometric Dissolved Oxygen Sensors Based on Ruthenium Complex Doped with Silver Nanoparticles.

A ratiometric optical sensor has been developed with electrospinning processing method for dissolved oxygen measurement. The sensing film is fabricated by using silver nano-particles (Ag NPs) doped with tris(4,7-diphenyl-1,10-phenanthroline) ruthenium(II) dichloride complex (Ru(DPP)3Cl2) encapsulated in plasticized polymethyl methacrylate (PMMA). An insensitive 3-(2-benzothiazolyl)-7-(diethy lamino)-(6CI,7CI) (Coumarin6) is adopted as reference. The ratio of oxygenation is calculated at each image pixel of a 3CCD camera to quantify the oxygen concentration in aqueous environment. Compared to Ag-free film, the response time of Ag-containing films were improved from 1.5 s to 1.0 s upon switching from deoxygenated to air saturation and from 65 s to 45 s from air saturation to fully deoxygenated. The response times of the Ag-free film obtained by knifing was 2.0 s upon switching from deoxygenated to air saturation and 104 s from air saturation to fully deoxygenated. Results of the evaluation of accuracy, limit of detection, stability, and photostability are presented. An experiment measuring the spatiotemporal variation of oxygen distribution within the photosynthesis and respiration of Chlorella vulgaris is demonstrated. It is shown that the nanofiber-based optical sensor film could serve as a promising method for rapid oxygen monitoring in aqueous applications.