Having adopted a dynamic zero-COVID strategy to respond to SARS-CoV-2 variants with higher transmissibility since August 2021, China is now considering whether, and for how long, this policy can remain in place. The debate has thus shifted towards the identification of mitigation strategies for minimizing disruption to the healthcare system in the case of a nationwide epidemic. To this aim, we developed an age-structured stochastic compartmental susceptible-latent-infectious-removed-susceptible model of SARS-CoV-2 transmission calibrated on the initial growth phase for the 2022 Omicron outbreak in Shanghai, to project COVID-19 burden (that is, number of cases, patients requiring hospitalization and intensive care, and deaths) under hypothetical mitigation scenarios. The model also considers age-specific vaccine coverage data, vaccine efficacy against different clinical endpoints, waning of immunity, different antiviral therapies and nonpharmaceutical interventions. We find that the level of immunity induced by the March 2022 vaccination campaign would be insufficient to prevent an Omicron wave that would result in exceeding critical care capacity with a projected intensive care unit peak demand of 15.6 times the existing capacity and causing approximately 1.55 million deaths. However, we also estimate that protecting vulnerable individuals by ensuring accessibility to vaccines and antiviral therapies, and maintaining implementation of nonpharmaceutical interventions could be sufficient to prevent overwhelming the healthcare system, suggesting that these factors should be points of emphasis in future mitigation policies.

A rapid and efficient approach for the preparation and modification of a versatile class of functional polymer nanoparticles has been developed, for which the entire engineering process from small molecules to polymers to nanoparticles bypasses typical slow and inefficient procedures, and rather employs a series of steps that capture fully the “click” chemistry concepts that have greatly facilitated the preparation of complex polymer materials over the past decade. The construction of various nanoparticles with functional complexity from a versatile platform is a challenging aim to provide materials for fundamental studies and also optimization toward a diverse range of applications. In this paper, we demonstrate the rapid and facile preparation of a family of nanoparticles with different surface charges and functionalities based on a biodegradable polyphosphoester block copolymer system. From a retrosynthetic point of view, the non-ionic, anionic, cationic and zwitterionic micelles with hydrodynamic diameters between 13 nm to 21 nm and great size uniformity were quickly formed by suspending, independently, four amphiphilic diblock polyphosphoesters into water, which were functionalized from the same parental hydrophobic-functional AB diblock polyphosphoester by “click” type thiol-yne reactions. The well-defined (PDI < 1.2) hydrophobic-functional AB diblock polyphosphoester was synthesized by an ultrafast (< 5 min) organocatalyzed ring-opening polymerization in a two-step, one-pot manner with the quantitative conversions of two kinds of cyclic phospholane monomers. The whole programmable process starting from small molecules to nanoparticles could be completed within 6 h, as the most rapid approach for the anionic and non-ionic nanoparticles, although the cationic and zwitterionic nanoparticles required ca. 2 days due to purification by dialysis. The micelles showed high biocompatibility, with even the cationic micelles exhibiting a 6-fold lower cytotoxicity toward RAW 264.7 mouse macrophage cells, as compared to the Lipofectamine® commercial transfection agent.

“Click” chemistry is a library of efficient and reliable reactions, which have been used to functionalize various classes of bio- and synthetic macromolecular systems for the incorporation of designed properties and functions. In this report, azide-alkyne Huisgen cycloaddition and thiol-yne reactions, two classical “click” chemistries, were employed to functionalize biodegradable, clickable polyphosphoester homopolymers and their water-soluble copolymers. A stable alkyne-functionalized phospholane monomer was synthesized, its organocatalyzed polymerization kinetics were evaluated, and the resulting (co)polymers were utilized to develop this facile method that provides the synthesis of clickable, water-soluble and degradable polyphosphoesters, which can be adapted for various applications.

Experimental SectionMeasurements. 1 H NMR (500 MHz) spectra were acquired in CDCl 3 using a Varian INOVA-500 spectrometer at 25 °C. Tetramethylsilane (TMS) was used as an internal reference for 1 H NMR spectroscopy. FT-IR spectra were obtained on a Bruker Tensor 27 system using attenuated total reflectance (ATR) sampling accessories. High resolution mass spectrum was obtained on a ThermoFinnigan MAT XL spectrometer.Matrix-assisted laser desorption/ionization time-of-flight mass spectrometery (MALDI-TOF) was measured on a Bruker Biflex IV (Billerica, MA) MALDI mass spectrometer equipped with a nitrogen laser (λ = 337 nm). Mass spectrum was acquired in the reflection mode with a mass range of 2000-12000 m/z, and the mass scale was calibrated externally using the peaks of peptide calibration standard II purchased from Bruker. Trans-2-[3-(4-tert-butylphenyl)-2-methyl-2-propenylidene]malononitrile (DCTB, Aldrich; ≥99%) served as matrix and was dissolved in CHCl 3 at a concentration of 20 mg/mL. Sodium trifluoroacetate (NaTFA, Aldrich; ~98%) served as cationizing agent and was dissolved in MeOH/CHCl 3 (1/3, v/v) at a concentration of 10 mg/mL. The polymer was dissolved in CHCl 3 at a concentration of 10 mg/mL. The matrix solution, polymer solution, and NaTFA solution were mixed in the ratio of 10/1/1 (v/v/v). The sample preparation involved depositing 1 μL of the mixture on the steel plate, and allowing the spot to dry.Gel permeation chromatography (GPC) was conducted using Viscotek GPC system equipped with a VE-3580 refractive index (RI) detector, a 270 dual detector system having a viscometer detector and a dual-angle (7 º and 90 º) laser light scattering (LS) detector, a VE 1122 pump, and two mixed-bed organic columns (PAS-103M with exclusion limit of 70 kDa and PAS-105M with exclusion limit of 4 MDa). N,N'-dimethylformamide (HPLC grade) with 0.1 M

Functional polylactide-g-paclitaxel–poly(ethylene glycol), a novel graft polymer–drug conjugate (GPDC) with paclitaxel (PTXL) as the divalent agent to bridge between the degradable polylactide (PLA)-based backbone and hydrophilic poly(ethylene glycol) (PEG) side chains, were prepared by the copper-catalyzed azide–alkyne cycloaddition reaction of acetylene-functionalized polylactide (PLA) with azide-functionalized PTXL–PEG conjugate. The acetylene-functionalized PLA was prepared by ring-opening copolymerization (ROCP) of acetylene-functionalized LA monomer with l-lactide (LA). The azide-functionalized PTXL–PEG conjugate was prepared by multistep organic synthesis. The well-controlled chemical structures of the GPDC and its precursors were verified by 1H NMR and GPC characterizations. DLS analysis indicated that GPDC molecules assembled in water to form nanoparticles with sizes of 8–40 nm. GPC analysis of buffer solutions (pH = 5.5 and 7.4) of the GPDC suggested the occurrence of multiple hydrolysis reactions under the experimental conditions, which resulted in the release of PTXL moieties and the cleavage of PLA-based backbone.