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Prior studies have focused on the overall behavior of randomly moving particle swarms. However, the characteristics of the stochastic-constrained particles that form ubiquitously within these swarms remain oblivious. This study demonstrates a generalized diffusion equation for stochastic-constrained particles that considers the velocity and location aggregation effects observed from their parent particle swarm (i.e., a completely random particle swarm). This equation can be approximated as the form of Schrödinger equation in the microcosmic case (low relative density) and describe the dynamics of the total mass distribution in the macrocosmic case (high relative density). The predicted density distribution of the particle swarm in the stable aggregation state is consistent with the total mass distribution of massive, relaxed galaxy clusters (at least in the range of r < r s ), preventing cuspy problems in the empirical Navarro–Frenk–White profile. This study opens a window to observe the dynamics of stochastic-constrained particles from a third perspective, from which the aggregation effect of particles without gravitation can be saw.

Particulate matter (PM) pollutants, including nanoscale particles (NPs), have been considered serious threats to public health. In this work, a self-powered air filter that can be used in high-efficiency removal of PM, including NPs, is presented. An ionic liquid–polymer (ILP) composite is irregularly distributed onto a sponge network to form an ILP@MF filter. Enabled by its unique electrochemical properties, the ILP@MF filter can remove PM 2.5 and PM 10 with high efficiencies of 99.59% and 99.75%, respectively, after applying a low voltage. More importantly, the charged ILP@MF filter realizes a superior removal for NPs with an efficiency of 93.77%. A micro-button lithium cell or silicon-based solar panel is employed as a power supply platform to fabricate a portable and self-powered face mask, which exhibits excellent efficacy in particulate removal compared to commercial masks. This work shows a great promise for high-performance purification devices and facile mask production to remove particulate pollutants. Particulate matter (PM) pollutants have been considered serious threats to public health but effective removal of nanoscale particles (NPs) by filter materials is challenging. Here, the authors fabricate an ionic liquid based self-powered air filter that can be used in high-efficiency removal of PM, including NPs.

It has been more than 100 years since the advent of special relativity, but the reasons behind the related phenomena are still unknown. This article aims to inspire people to think about such problems. With the help of Mathematica software, I have proven the following problem by means of statistics: In 3-dimensional Euclidean space, for point particles whose speeds are c and whose directions are uniformly distributed in space (assuming these particles’ reference system is R 0 , if their average velocity is 0), when some particles (assuming their reference system is R u ), as a particle swarm, move in a certain direction with a group speed u (i.e., the norm of the average velocity) relative to R 0 , their (or the sub-particle swarm’s) average speed relative to R u is slower than that of particles (or the same scale sub-particle swarm) in R 0 relative to R 0 . The degree of slowing depends on the speed u of R u and accords with the quantitative relationship described by the Lorentz factor c c 2 - u 2 . Base on this conclusion, I have deduced the speed distribution of particles in R u when observing from R 0 .

Persistent hepatitis B virus (HBV) infection relies on the establishment and maintenance of covalently closed circular (ccc) DNA, a 3.2 kb episome that serves as a viral transcription template, in the nucleus of an infected hepatocyte. Although evidence suggests that cccDNA is the repair product of nucleocapsid associated relaxed circular (rc) DNA, the cellular DNA polymerases involving in repairing the discontinuity in both strands of rcDNA as well as the underlying mechanism remain to be fully understood. Taking a chemical genetics approach, we found that DNA polymerase alpha (Pol α) is essential for cccDNA intracellular amplification, a genome recycling pathway that maintains a stable cccDNA pool in infected hepatocytes. Specifically, inhibition of Pol α by small molecule inhibitors aphidicolin or CD437 as well as silencing of Pol α expression by siRNA led to suppression of cccDNA amplification in human hepatoma cells. CRISPR-Cas9 knock-in of a CD437-resistant mutation into Pol α genes completely abolished the effect of CD437 on cccDNA formation, indicating that CD437 directly targets Pol α to disrupt cccDNA biosynthesis. Mechanistically, Pol α is recruited to HBV rcDNA and required for the generation of minus strand covalently closed circular rcDNA, suggesting that Pol α is involved in the repair of the minus strand DNA nick in cccDNA synthesis. Our study thus reveals that the distinct host DNA polymerases are hijacked by HBV to support the biosynthesis of cccDNA from intracellular amplification pathway compared to that from de novo viral infection, which requires Pol κ and Pol λ.

Covalent organic frameworks show great potential in gas adsorption/separation, biomedicine, device, sensing, and printing arenas. However, covalent organic frameworks are generally not dispersible in common solvents resulting in the poor processability, which severely obstruct their application in practice. In this study, we develop a convenient top-down process for fabricating solution-processable covalent organic frameworks by introducing intermolecular hydrogen bonding and π-π interactions from ionic liquids. The bulk powders of imine-linked, azine-linked, and β -ketoenamine linked covalent organic frameworks can be dispersed homogeneously in optimal ionic liquid 1-methyl-3-octylimidazolium bromide after heat treatment. The resulting high-concentration colloids are utilized to create the covalent organic framework inks that can be directly printed onto the surface. Molecular dynamics simulations and the quantum mechanical calculations suggest that C‒H···π and π-π interaction between ionic liquid cations and covalent organic frameworks may promote the formation of colloidal solution. These findings offer a roadmap for preparing solution-processable covalent organic frameworks, enabling their practical applications. Covalent organic frameworks are generally not dispersible in common solvents resulting in the poor processability which limits their practical application. Here, the authors develop a top-down process to produce solution-processable covalent organic frameworks based on the assistance of ionic liquids by means of intermolecular hydrogen bonding and π-π interactions.

Hepatitis B virus (HBV) core protein assembles viral pre-genomic (pg) RNA and DNA polymerase into nucleocapsids for reverse transcriptional DNA replication to take place. Several chemotypes of small molecules, including heteroaryldihydropyrimidines (HAPs) and sulfamoylbenzamides (SBAs), have been discovered to allosterically modulate core protein structure and consequentially alter the kinetics and pathway of core protein assembly, resulting in formation of irregularly-shaped core protein aggregates or \"empty\" capsids devoid of pre-genomic RNA and viral DNA polymerase. Interestingly, in addition to inhibiting nucleocapsid assembly and subsequent viral genome replication, we have now demonstrated that HAPs and SBAs differentially modulate the biosynthesis of covalently closed circular (ccc) DNA from de novo infection and intracellular amplification pathways by inducing disassembly of nucleocapsids derived from virions as well as double-stranded DNA-containing progeny nucleocapsids in the cytoplasm. Specifically, the mistimed cuing of nucleocapsid uncoating prevents cccDNA formation during de novo infection of hepatocytes, while transiently accelerating cccDNA synthesis from cytoplasmic progeny nucleocapsids. Our studies indicate that elongation of positive-stranded DNA induces structural changes of nucleocapsids, which confers ability of mature nucleocapsids to bind CpAMs and triggers its disassembly. Understanding the molecular mechanism underlying the dual effects of the core protein allosteric modulators on nucleocapsid assembly and disassembly will facilitate the discovery of novel core protein-targeting antiviral agents that can more efficiently suppress cccDNA synthesis and cure chronic hepatitis B.

Hepatitis B virus (HBV) replicates its DNA genome through reverse transcription of a viral RNA pregenome. We report herein that the interferon (IFN) stimulated exoribonuclease gene of 20 KD (ISG20) inhibits HBV replication through degradation of HBV RNA. ISG20 expression was observed at basal level and was highly upregulated upon IFN treatment in hepatocytes, and knock down of ISG20 resulted in elevation of HBV replication and attenuation of IFN-mediated antiviral effect. The sequence element conferring the susceptibility of HBV RNA to ISG20-mediated RNA degradation was mapped at the HBV RNA terminal redundant region containing epsilon (ε) stem-loop. Furthermore, ISG20-induced HBV RNA degradation relies on its ribonuclease activity, as the enzymatic inactive form ISG20D94G was unable to promote HBV RNA decay. Interestingly, ISG20D94G retained antiviral activity against HBV DNA replication by preventing pgRNA encapsidation, resulting from a consequence of ISG20-ε interaction. This interaction was further characterized by in vitro electrophoretic mobility shift assay (EMSA) and ISG20 was able to bind HBV ε directly in absence of any other cellular proteins, indicating a direct ε RNA binding capability of ISG20; however, cofactor(s) may be required for ISG20 to efficiently degrade ε. In addition, the lower stem portion of ε is the major ISG20 binding site, and the removal of 4 base pairs from the bottom portion of ε abrogated the sensitivity of HBV RNA to ISG20, suggesting that the specificity of ISG20-ε interaction relies on both RNA structure and sequence. Furthermore, the C-terminal Exonuclease III (ExoIII) domain of ISG20 was determined to be responsible for interacting with ε, as the deletion of ExoIII abolished in vitro ISG20-ε binding and intracellular HBV RNA degradation. Taken together, our study sheds light on the underlying mechanisms of IFN-mediated HBV inhibition and the antiviral mechanism of ISG20 in general.

Regulatory T cell (Treg)-mediated immunosuppression represents one of the crucial tumor immune evasion mechanisms and is a main obstacle for successful tumor immunotherapy. Hypoxia, a common feature of solid tumors, has been associated with potentiated immunosuppression, decreased therapeutic response, malignant progression and local invasion. Unfortunately, the link between hypoxia and Treg-mediated immune tolerance in gastric cancer remains poorly understood. In our study, Tregs and hypoxia inducible factor-1α were found to be positively correlated with each other and were increased with the tumor progression. A subsequent in vitro study indicated that supernatants derived from gastric cancer cells under hypoxic condition, could induce the expression of Foxp3 via TGF-β1. These findings confirmed the crucial role of Tregs as a therapeutic target in gastric cancer therapy and provided helpful thoughts for the design of immunotherapy for gastric cancer in the future.

The zinc finger antiviral protein (ZAP) is a mammalian host restriction factor that inhibits the replication of a variety of RNA viruses, including retroviruses, alphaviruses and filoviruses, through interaction with the ZAP-responsive elements (ZRE) in viral RNA, and recruiting the exosome to degrade RNA substrate. Hepatitis B virus (HBV) is a pararetrovirus that replicates its genomic DNA via reverse transcription of a viral pregenomic (pg) RNA precursor. Here, we demonstrate that the two isoforms of human ZAP (hZAP-L and -S) inhibit HBV replication in human hepatocyte-derived cells through posttranscriptional down-regulation of viral pgRNA. Mechanistically, the zinc finger motif-containing N-terminus of hZAP is responsible for the reduction of HBV RNA, and the integrity of the four zinc finger motifs is essential for ZAP to bind to HBV RNA and fulfill its antiviral function. The ZRE sequences conferring the susceptibility of viral RNA to ZAP-mediated RNA decay were mapped to the terminal redundant region (nt 1820-1918) of HBV pgRNA. In agreement with its role as a host restriction factor and as an innate immune mediator for HBV infection, ZAP was upregulated in cultured primary human hepatocytes and hepatocyte-derived cells upon IFN-α treatment or IPS-1 activation, and in the livers of hepatitis B patients during immune active phase. Knock down of ZAP expression increased the level of HBV RNA and partially attenuated the antiviral effect elicited by IPS-1 in cell cultures. In summary, we demonstrated that ZAP is an intrinsic host antiviral factor with activity against HBV through down-regulation of viral RNA, and that ZAP plays a role in the innate control of HBV replication. Our findings thus shed light on virus-host interaction, viral pathogenesis, and antiviral approaches.

Insertions and deletions (Indels) represent one of the major variation types in the human genome and have been implicated in diseases including cancer. To study the features of somatic indels in different cancer genomes, we investigated the indels from two large samples of cancer types: invasive breast carcinoma (BRCA) and lung adenocarcinoma (LUAD). Besides mapping somatic indels in both coding and untranslated regions (UTRs) from the cancer whole exome sequences, we investigated the overlap between these indels and transcription factor binding sites (TFBSs), the key elements for regulation of gene expression that have been found in both coding and non-coding sequences. Compared to the germline indels in healthy genomes, somatic indels contain more coding indels with higher than expected frame-shift (FS) indels in cancer genomes. LUAD has a higher ratio of deletions and higher coding and FS indel rates than BRCA. More importantly, these somatic indels in cancer genomes tend to locate in sequences with important functions, which can affect the core secondary structures of proteins and have a bigger overlap with predicted TFBSs in coding regions than the germline indels. The somatic CDS indels are also enriched in highly conserved nucleotides when compared with germline CDS indels.