Jianhua Lu

Biologics, including proteins and antisense oligonucleotides (ASOs), face significant challenges when it comes to achieving intracellular delivery within specific organs or cells through systemic administrations. In this study, we present a novel approach for delivering proteins and ASOs to liver cells, both in vitro and in vivo, using conjugates that tether N-acetylated galactosamine (GalNAc)-functionalized, cell-penetrating polydisulfides (PDSs). The method involves the thiol-bearing cargo-mediated ring-opening polymerization of GalNAc-functionalized lipoamide monomers through the so-called aggregation-induced polymerization, leading to the formation of site-specific protein/ASO-PDS conjugates with narrow dispersity. The hepatocyte-selective intracellular delivery of the conjugates arises from a combination of factors, including first GalNAc binding with ASGPR receptors on liver cells, leading to cell immobilization, and the subsequent thiol–disulfide exchange occurring on the cell surface, promoting internalization. Our findings emphasize the critical role of the close proximity of the PDS backbone to the cell surface, as it governs the success of thiol–disulfide exchange and, consequently, cell penetration. These conjugates hold tremendous potential in overcoming the various biological barriers encountered during systemic and cell-specific delivery of biomacromolecular cargos, opening up new avenues for the diagnosis and treatment of a range of liver-targeting diseases.

Abstract Since the last IAEA-FEC in 2021, significant progress on the development of long pulse steady state scenario and its related key physics and technologies have been achieved, including the reproducible 403 s long-pulse steady-state H-mode plasma with pure radio frequency (RF) power heating. A thousand-second time scale (∼1056 s) fully non-inductive plasma with high injected energy up to 1.73 GJ has also been achieved. The EAST operational regime of high β P has been significantly extended ( H 98y2 > 1.3, β P ∼ 4.0, β N ∼ 2.4 and n e / n GW ∼ 1.0) using RF and neutral beam injection (NBI). The full edge localized mode suppression using the n = 4 resonant magnetic perturbations has been achieved in ITER-like standard type-I ELMy H-mode plasmas with q 95 ≈ 3.1 on EAST, extrapolating favorably to the ITER baseline scenario. The sustained large ELM control and stable partial detachment have been achieved with Ne seeding. The underlying physics of plasma-beta effect for error field penetration, where toroidal effect dominates, is disclosed by comparing the results in cylindrical theory and MARS-Q simulation in EAST. Breakdown and plasma initiation at low toroidal electric fields (<0.3 V m −1 ) with EC pre-ionization is developed. A beneficial role on the lower hybrid wave injection to control the tungsten concentration in the NBI discharge is observed for the first time in EAST suggesting a potential way toward steady-state H-mode NBI operation.

What is already known about this topic?: Aerosol transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via sanitary pipelines in high-rise buildings is possible, however, there is a lack of experimental evidence. What is added by this report?: The field simulation experiment confirmed the existence of a vertical aerosol transmission pathway from toilet flush-soil stack-floor drains without water seal. This report provided experimental evidence for vertical aerosol transmission of clustered outbreaks on 18 floors of a 33-story residential building. What are the implications for public health practice?: The water seal on floor drains is a necessary barrier to prevent the risk of vertical aerosol transmission of infectious disease pathogens in buildings. It is necessary not only to have a U-shaped trap in the drainage pipe, but also to be filled with water regularly.

This paper comprehensively analyses the first-ever monkeypox outbreak in Shenzhen, China, encompassing clinical symptomatology, therapeutic approaches, epidemiological research, and comprehensive laboratory tests, aiming to establish a robust reference for future monkeypox mitigation and management strategies. The investigation involved a thorough investigation of all identified positive cases, including extensive molecular analysis by nucleic acid detection and whole-genome sequencing of the monkeypox virus. Contact tracing and containment of the infected individuals were also undertaken. Three distinct monkeypox cases were identified in this unique outbreak, exhibiting mild and atypical clinical manifestations, primarily fever and rash. All cases were associated with a single transmission chain, primarily facilitated through close contact and homosexual behavior, indicative of a high-risk factor for monkeypox transmission.

The transmission chains were clear in this epidemic. The incubation period of Omicron variant BF.7 infection was shorter, the transmission speed was faster, and the gene mutation rate was higher. It is necessary to conduct prompt response and strict disease control when epidemic occurs.