The faithful storage and coherent manipulation of quantum states with matter-systems would enable the realization of large-scale quantum networks based on quantum repeaters. To achieve useful ...communication rates, highly multimode quantum memories are required to construct a multiplexed quantum repeater. Here, we present a demonstration of on-demand storage of orbital-angular-momentum states with weak coherent pulses at the single-photon-level in a rare-earth-ion-doped crystal. Through the combination of this spatial degree-of-freedom (DOF) with temporal and spectral degrees of freedom, we create a multiple-DOF memory with high multimode capacity. This device can serve as a quantum mode converter with high fidelity, which is a fundamental requirement for the construction of a multiplexed quantum repeater. This device further enables essentially arbitrary spectral and temporal manipulations of spatial-qutrit-encoded photonic pulses in real time. Therefore, the developed quantum memory can serve as a building block for scalable photonic quantum information processing architectures.
Zika virus (ZIKV) has become a public health threat due to its global transmission and link to severe congenital disorders. The host immune responses to ZIKV infection have not been fully elucidated, ...and effective therapeutics are not currently available. Herein, we demonstrated that cholesterol-25-hydroxylase (CH25H) was induced in response to ZIKV infection and that its enzymatic product, 25-hydroxycholesterol (25HC), was a critical mediator of host protection against ZIKV. Synthetic 25HC addition inhibited ZIKV infection in vitro by blocking viral entry, and treatment with 25HC reduced viremia and conferred protection against ZIKV in mice and rhesus macaques. 25HC suppressed ZIKV infection and reduced tissue damage in human cortical organoids and the embryonic brain of the ZIKV-induced mouse microcephaly model. Our findings highlight the protective role of CH25H during ZIKV infection and the potential use of 25HC as a natural antiviral agent to combat ZIKV infection and prevent ZIKV-associated outcomes, such as microcephaly.
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•CH25H and its enzymatic product, 25HC, inhibit ZIKV entry in vitro•25HC attenuates ZIKV-associated viremia and disease in mice and non-human primates•25HC prevents ZIKV infection in human cortical organoids•25HC protects fetal mice from microcephaly caused by ZIKV infection
Zika virus (ZIKV) presents a major challenge to the global health system. Li et al. find that 25-hydroxycholesterol (25HC) inhibits ZIKV infection in monkeys and human cortical organoids and protects mice from microcephaly. 25HC has potential as a first-line antiviral agent to combat a broad array of pathogenic species, including ZIKV.
Hypoxia and the Tumor Microenvironment Li, Yue; Zhao, Long; Li, Xiao-Feng
Technology in Cancer Research & Treatment,
2021, Volume:
20
Book Review, Journal Article
Peer reviewed
Open access
Hypoxia is an important feature of the tumor microenvironment, and is closely associated with cell proliferation, angiogenesis, metabolism and the tumor immune response. All these factors can further ...promote tumor progression, increase tumor aggressiveness, enhance tumor metastatic potential and lead to poor prognosis. In this review, these effects of hypoxia on tumor biology will be discussed, along with their significance for tumor detection and treatment.
Current enzyme‐responsive, fluorogenic probes fail to provide in situ information because the released fluorophores tend to diffuse away from the reaction sites. The problem of diffusive signal ...dilution can be addressed by designing a probe that upon enzyme conversion releases a fluorophore that precipitates. An excited‐state intramolecular proton transfer (ESIPT)‐based solid‐state fluorophore HTPQ was developed that is strictly insoluble in water and emits intense fluorescence in the solid state, with λex/em=410/550 nm, thus making it far better suited to use with a commercial confocal microscope. HTPQ was further utilized in the design of an enzyme‐responsive, fluorogenic probe (HTPQA), targeting alkaline phosphatase (ALP) as a model enzyme. HTPQA makes possible diffusion‐resistant in situ detection of endogenous ALP in live cells. It was also employed in the visualizing of different levels of ALP in osteosarcoma cells and tissue, thus demonstrating its interest for the diagnosis of this type of cancer.
A solid‐state fluorophore (HTPQ) that is well‐suited to confocal microscopy was developed. HTPQ was used to design an enzyme‐responsive, fluorogenic probe (HTPQA) targeting alkaline phosphatase (ALP) as a model enzyme. HTPQA makes possible diffusion‐resistant detection of endogenous ALP in live cells and visualization of ALP levels in Saos‐2 and U‐2OS osteosarcoma cells and tissue.
Acute organ injury observed during sepsis, caused by an uncontrolled release of inflammatory mediators, such as lipopolysaccharide (LPS), is quite fatal. The development of efficient methods for ...early diagnosis of sepsis and LPS-induced acute organ injury in living systems is of great biomedical importance. In living systems, cystathionine γ-lyase (CSE) can be overexpressed due to LPS, and H2S n can be formed by CSE-mediated cysteine metabolism. Thus, acute organ injury during sepsis may be correlated with H2S n levels, making accurate detection of H2S n in living systems of great physiological and pathological significance. In this work, our previously reported fluorescent platform was employed to design and synthesize a FRET-based ratiometric two-photon (TP) fluorescent probe TPR-S, producing a large emission shift in the presence of H2S n . In this work, a naphthalene derivative two-photon fluorophore was chosen as the energy donor; a rhodol derivative fluorophore served as the acceptor. The 2-fluoro-5-nitrobenzoate group of probe TPR-S reacted with H2S n and was selectively removed to release the fluorophore, resulting in a fluorescent signal decrease at 448 nm and enhancement at 541 nm. The ratio value of the fluorescence intensity between 541 and 448 nm (I 541 nm/I 448 nm) varied from 0.13 to 8.12 (∼62-fold), with the H2S n concentration changing from 0 to 1 mM. The detection limit of the probe was 0.7 μM. Moreover, the probe was applied for imaging H2S n in living cells, tissues, and organs of LPS-induced acute organ injury, which demonstrated its practical application in complex biosystems as a potential method to achieve early diagnosis of LPS-induced acute organ injury.
Growing experimental and clinical evidence suggests that a chronic inflammatory response induced by gut microbiome critically contribute to the development of rheumatoid arthritis (RA). Previous ...studies demonstrated the disturbance of lymphocyte subpopulations in RA patients. The purpose of this study was to explore the characteristics of gut microbiome and the associations between bacterium and lymphocyte subpopulations as well as cytokines in patients with RA. Fecal samples from 205 RA patients and 199 healthy controls (HCs) were collected for bacterial DNA extraction and 16S ribosomal RNA (rRNA) gene sequencing. The levels of peripheral lymphocyte subpopulation such as T, B, CD4+T, CD8+T, NK, T helper 1 (Th1), Th2, Th17, and regulatory T cells (Tregs) of these subjects were detected by flow cytometry combined with standard absolute counting beads. The serum levels of cytokines interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-17, tumour necrosis factor-α (TNF-α), and interferon-γ (INF-γ) were tested by flow cytometric bead array (CBA). Alpha and beta diversity of gut microbiome were explored by bioinformatics analysis. Spearman rank correlation test was used to explore the relationships between gut microbiome and lymphocyte subsets as well as serum cytokines. The diversity and relative abundance of intestinal microbiota in patients with RA were significantly different from those in HCs. Detailly, the abundant of phylum Proteobacteria in RA patients was more than that in HCs, while Firmicutes was less than in HCs. There was increased relative abundance of genus Clostridium_XlVa as well as genus Blautia, more abundance of Ruminococcus2 in patients with lower levels of T, B, CD4+T, and Tregs. In addition, the relative abundances of Pelagibacterium, Oxalobacter, ClostridiumXlVb, and ClostridiumXVIII were correlated with cytokines. Gut microbiome of RA patients was clearly different from that of HCs. Abnormal bacteria communities are associated with the altered levels of lymphocyte subpopulation and cytokines, which might be one of the pathogenesis of RA.
Zika virus (ZIKV) has evolved into a global health threat because of its unexpected causal link to microcephaly. Phylogenetic analysis reveals that contemporary epidemic strains have accumulated ...multiple substitutions from their Asian ancestor. Here we show that a single serine-to-asparagine substitution Ser139→Asn139 (S139N) in the viral polyprotein substantially increased ZIKV infectivity in both human and mouse neural progenitor cells (NPCs) and led to more severe microcephaly in the mouse fetus, as well as higher mortality rates in neonatal mice. Evolutionary analysis indicates that the S139N substitution arose before the 2013 outbreak in French Polynesia and has been stably maintained during subsequent spread to the Americas. This functional adaption makes ZIKV more virulent to human NPCs, thus contributing to the increased incidence of microcephaly in recent ZIKV epidemics.
Nontoxic prodrugs, especially activated by tumor microenvironment, are urgently required for reducing the side effects of cancer therapy. And combination of chemo-photodynamic therapy prodrugs show ...effectively synergetic therapeutic efficiency, however, this goal has not been achieved in a single molecule. In this work, we developed a mitochondrial-targeted prodrug
for near infrared (NIR) fluorescence imaging guided and synergetic chemo-photodynamic precise cancer therapy for the first time.
contains a NIR photosensitizer (
) and an anticancer drug 5'-deoxy-5-fluorouridine (5'-DFUR). These two parts are linked and caged through a bisboronate group, displaying no fluorescence and very low cytotoxicity. In the presence of H
O
, the bisboronate group is broken, resulting in activation of
for NIR photodynamic therapy and activation of 5'-DFUR for chemotherapy. The activated
can also provide a NIR fluorescence signal for monitoring the release of activated drug. Taking advantage of the high H
O
concentration in cancer cells,
exhibits higher cytotoxicity to cancer cells than normal cells, resulting in lower side effects. In addition, based on its mitochondrial-targeted ability,
exhibits enhanced chemotherapy efficiency compare to free 5'-DFUR. It also demonstrated a remarkably improved and synergistic chemo-photodynamic therapeutic effect for cancer cells. Moreover,
exhibits excellent tumor microenvironment-activated performance when intravenously injected into tumor-bearing nude mice, as demonstrated by
fluorescence imaging. Thus,
is a promising prodrug for cancer therapy based on its tumor microenvironment-activated drug release, synergistic therapeutic effect and "turn-on" NIR imaging guide.
There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as ...a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV). Intramuscular immunization of ARCoV mRNA-LNP elicited robust neutralizing antibodies against SARS-CoV-2 as well as a Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain. Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1 week. ARCoV is currently being evaluated in phase 1 clinical trials.
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•Development of LNP-encapsulated mRNA vaccine (ARCoV) targeting the RBD of SARS-CoV-2•ARCoV induces neutralizing antibodies and T cell immunity in mice and NHPs•ARCoV vaccination confers full protection against SARS-CoV-2 challenge in mice•ARCoV is a thermostable vaccine candidate for phase I studies
ARCoV is an LNP-encapsulated mRNA vaccine platform that is highly immunogenic and safe in mice and non-human primates, conferring protection against challenge with a SARS-CoV-2 mouse-adapted strain.
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