Thousands of genes have been well demonstrated to play important roles in cancer progression. As genes do not function in isolation, they can be grouped into "networks" based on their interactions. ...In this study, we discover a network regulating Claudin-4 in gastric cancer. We observe that Claudin-4 is up-regulated in gastric cancer and is associated with poor prognosis. Claudin-4 reinforce proliferation, invasion, and EMT in AGS, HGC-27, and SGC-7901 cells, which could be reversed by miR-596 and miR-3620-3p. In addition, lncRNA-KRTAP5-AS1 and lncRNA-TUBB2A could act as competing endogenous RNAs to affect the function of Claudin-4. Our results suggest that non-coding RNAs play important roles in the regulatory network of Claudin-4. As such, non-coding RNAs should be considered as potential biomarkers and therapeutic targets against gastric cancer.Non-coding RNAs can modify the expression of proteins in cancer networks. Here the authors reveal a regulatory network in gastric cancer whereby claudin-4 expression is reduced by specific miRNAs, which are in turn bound by specific lncRNAs acting as competing endogenous RNAs (ceRNAs), resulting in increased claudin-4 expression.
Low‐dimensional lead halide perovskite materials recently have drawn much attention owing to the intriguing broadband emissions; however, the toxicity of lead will hinder their future development. ...Now, a lead‐free (C4H14N2)2In2Br10 single crystal with a unique zero‐dimensional (0D) structure constituted by InBr63− octahedral and InBr4− tetrahedral units is described. The single crystal exhibits broadband photoluminescence (PL) that spans almost the whole visible spectrum with a lifetime of 3.2 μs. Computational and experimental studies unveil that an excited‐state structural distortion in InBr63− octahedral units enables the formation of intrinsic self‐trapped excitons (STEs) and thus contributing the broad emission. Furthermore, femtosecond transient absorption (fs‐TA) measurement reveals that the ultrafast STEs formation together with an efficient intersystem crossing has made a significant contribution to the long‐lived and broad STE‐based emission behavior.
A lead‐free indium‐based (C4H14N2)2In2Br10 single crystal was synthesized and characterized; it has a unique 0D crystal structure. An intrinsic self‐trapped exciton‐based ultra‐broad photoluminescence has been observed as a result of an excited‐state structural distortion in InBr63− octahedrons.
Although clinical studies have shown promise for targeting programmed cell death protein-1 (PD-1) and ligand (PD-L1) signaling in non-small cell lung cancer (NSCLC), the factors that predict which ...subtype patients will be responsive to checkpoint blockade are not fully understood.
We performed an integrated analysis on the multiple-dimensional data types including genomic, transcriptomic, proteomic, and clinical data from cohorts of lung adenocarcinoma public (discovery set) and internal (validation set) database and immunotherapeutic patients. Gene set enrichment analysis (GSEA) was used to determine potentially relevant gene expression signatures between specific subgroups.
We observed that
mutation significantly increased expression of immune checkpoints and activated T-effector and interferon-γ signature. More importantly, the
comutated subgroup manifested exclusive increased expression of PD-L1 and a highest proportion of
Meanwhile,
or
-mutated tumors showed prominently increased mutation burden and specifically enriched in the transversion-high (TH) cohort. Further analysis focused on the potential molecular mechanism revealed that
or
mutation altered a group of genes involved in cell-cycle regulating, DNA replication and damage repair. Finally, immunotherapeutic analysis from public clinical trial and prospective observation in our center were further confirmed that
or
mutation patients, especially those with co-occurring
mutations, showed remarkable clinical benefit to PD-1 inhibitors.
This work provides evidence that
and
mutation in lung adenocarcinoma may be served as a pair of potential predictive factors in guiding anti-PD-1/PD-L1 immunotherapy.
.
Low‐dimensional luminescent lead halide perovskites have attracted tremendous attention for their fascinating optoelectronic properties, while the toxicity of lead is still considered a drawback. ...Herein, we report a novel lead‐free zero‐dimensional (0D) indium‐based perovskite (Cs2InBr5⋅H2O) single crystal that is red‐luminescent with a high photoluminescence quantum yield (PLQY) of 33 %. Experimental and computational studies reveal that the strong PL emission might originate from self‐trapping excitons (STEs) that result from an excited‐state structural deformation. More importantly, the in situ transformation between hydrated Cs2InBr5⋅H2O and the dehydrated form is accompanied with a switchable dual emission, which enables it to act as a PL water‐sensor in humidity detection or the detection of traces of water in organic solvents.
Unleaded and unleashed: A highly emissive lead‐free indium‐based perovskite single crystal, Cs2InBr5⋅H2O, was successfully prepared. The versatile material is the first reversible metal halide perovskite photoluminescence water sensor and paves the way for the application of metal halide perovskites in water detection.
All‐inorganic bismuth‐halide perovskites are promising alternatives for lead halide perovskites due to their admirable chemical stability and optoelectronic properties; however, these materials ...deliver inferior photoluminescence (PL) properties, severely hindering their prospects in lighting applications. Here, a novel air‐stable but non‐emissive perovskite Rb3BiCl6 is synthesized, and the material is used as a prototype to uncover origin of the poor optical performance in bismuth‐halide perovskite. It is found that the extremely strong exciton–phonon interactions with a large coupling constant up to 693 meV leads to the seriously nonradiative recombination, which, however, can be effectively suppressed to 347 meV by introducing Sb3+ ions. As a result, Sb3+‐doped Rb3BiCl6 exhibits a stable yellow emission with unprecedented PL quantum yield up to 33.6% from self‐trapped excitons. Systematic spectroscopic characterizations and theoretical calculations are carried out to unveil the intriguing photophysical mechanisms. This work reveals the effect of exciton–phonon interaction, that is often underemphasized, on a material's photophysical properties.
All‐inorganic lead‐free bismuth‐halide perovskite with excellent structural stability shows inferior photoluminescence performance due to the extremely strong exciton–phonon interaction, which however can be effectively suppressed by an ion doping strategy. This work provides a new avenue for the development of high‐performance luminous perovskites (or metal halides) by manipulating the exciton–phonon interaction.
For decades, poly(ethylene glycol) (PEG) has been widely incorporated into nanoparticles for evading immune clearance and improving the systematic circulation time. However, recent studies have ...reported a phenomenon known as “accelerated blood clearance (ABC)” where a second dose of PEGylated nanomaterials is rapidly cleared when given several days after the first dose. Herein, we demonstrate that natural red blood cell (RBC) membrane is a superior alternative to PEG. Biomimetic RBC membrane‐coated Fe3O4 nanoparticles (Fe3O4@RBC NPs) rely on CD47, which is a “don't eat me” marker on the RBC surface, to escape immune clearance through interactions with the signal regulatory protein‐alpha (SIRP‐α) receptor. Fe3O4@RBC NPs exhibit extended circulation time and show little change between the first and second doses, with no ABC suffered. In addition, the administration of Fe3O4@RBC NPs does not elicit immune responses on neither the cellular level (myeloid‐derived suppressor cells (MDSCs)) nor the humoral level (immunoglobulin M and G (IgM and IgG)). Finally, the in vivo toxicity of these cell membrane‐camouflaged nanoparticles is systematically investigated by blood biochemistry, hematology testing, and histology analysis. These findings are significant advancements toward solving the long‐existing clinical challenges of developing biomaterials that are able to resist both immune response and rapid clearance.
Red blood cell membrane‐camouflaged Fe3O4 nanoparticles (Fe3O4@RBC NPs) exhibit prolonged circulation time in the blood with no adverse effects. There is little change between a first and second dose, and no accelerated blood clearance is seen, as is generally the case for PEGylated nanomaterials. This is a significant advancement toward developing biomaterials that are able to resist both immune response and rapid clearance.
Although arthropods are important viral vectors, the biodiversity of arthropod viruses, as well as the role that arthropods have played in viral origins and evolution, is unclear. Through RNA ...sequencing of 70 arthropod species we discovered 112 novel viruses that appear to be ancestral to much of the documented genetic diversity of negative-sense RNA viruses, a number of which are also present as endogenous genomic copies. With this greatly enriched diversity we revealed that arthropods contain viruses that fall basal to major virus groups, including the vertebrate-specific arenaviruses, filoviruses, hantaviruses, influenza viruses, lyssaviruses, and paramyxoviruses. We similarly documented a remarkable diversity of genome structures in arthropod viruses, including a putative circular form, that sheds new light on the evolution of genome organization. Hence, arthropods are a major reservoir of viral genetic diversity and have likely been central to viral evolution.
Cancer cell membrane‐coated upconversion nanoprobes (CC‐UCNPs) with immune escape and homologous targeting capabilities are used for highly specific tumor imaging. The combination of UCNPs with ...biomimetic cancer cell membranes embodies a novel materials design strategy and presents a compelling class of advanced materials.
COVID-19 has spread worldwide since 2019 and is now a severe threat to public health. We previously identified the causative agent as a novel SARS-related coronavirus (SARS-CoV-2) that uses human ...angiotensin-converting enzyme 2 (hACE2) as the entry receptor. Here, we successfully developed a SARS-CoV-2 hACE2 transgenic mouse (HFH4-hACE2 in C3B6 mice) infection model. The infected mice generated typical interstitial pneumonia and pathology that were similar to those of COVID-19 patients. Viral quantification revealed the lungs as the major site of infection, although viral RNA could also be found in the eye, heart, and brain in some mice. Virus identical to SARS-CoV-2 in full-genome sequences was isolated from the infected lung and brain tissues. Last, we showed that pre-exposure to SARS-CoV-2 could protect mice from severe pneumonia. Our results show that the hACE2 mouse would be a valuable tool for testing potential vaccines and therapeutics.
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•SARS-CoV-2 could infect HFH4-hACE2 mice and cause death•SARS-CoV-2 infection localizes to lungs of mice and causes typical interstitial pneumonia•Pre-exposure to SARS-CoV-2 protects mice from lethal challenge
A SARS-CoV-2 hACE2 transgenic mouse infection model recapitulates a number of infection symptoms and pathology in COVID-19 patients. Pre-exposure to SARS-CoV-2 was able to protect mice from severe pneumonia.
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