Dampening of ISGylation of RIG-I by ADAP regulates type I interferon response of macrophages to RNA virus infection.

While macrophage is one of the major type I interferon (IFN-I) producers in multiple tissues during viral infections, it also serves as an important target cell for many RNA viruses. However, the regulatory mechanism for the IFN-I response of macrophages to respond to a viral challenge is not fully understood. Here we report ADAP, an immune adaptor protein, is indispensable for the induction of the IFN-I response of macrophages to RNA virus infections via an inhibition of the conjugation of ubiquitin-like ISG15 (ISGylation) to RIG-I. Loss of ADAP increases RNA virus replication in macrophages, accompanied with a decrease in LPS-induced IFN-ß and ISG15 mRNA expression and an impairment in the RNA virus-induced phosphorylation of IRF3 and TBK1. Moreover, using Adap-/- mice, we show ADAP deficiency strongly increases the susceptibility of macrophages to RNA-virus infection in vivo. Mechanically, ADAP selectively interacts and functionally cooperates with RIG-I but not MDA5 in the activation of IFN-ß transcription. Loss of ADAP results in an enhancement of ISGylation of RIG-I, whereas overexpression of ADAP exhibits the opposite effect in vitro, indicating ADAP is detrimental to the RNA virus-induced ISGylation of RIG-I. Together, our data demonstrate a novel antagonistic activity of ADAP in the cell-intrinsic control of RIG-I ISGylation, which is indispensable for initiating and sustaining the IFN-I response of macrophages to RNA virus infections and replication.

Layered nanocomposites by shear-flow-induced alignment of nanosheets.

Biological materials, such as bones, teeth and mollusc shells, are well known for their excellent strength, modulus and toughness1-3. Such properties are attributed to the elaborate layered microstructure of inorganic reinforcing nanofillers, especially two-dimensional nanosheets or nanoplatelets, within a ductile organic matrix4-6. Inspired by these biological structures, several assembly strategies-including layer-by-layer4,7,8, casting9,10, vacuum filtration11-13 and use of magnetic fields14,15-have been used to develop layered nanocomposites. However, how to produce ultrastrong layered nanocomposites in a universal, viable and scalable manner remains an open issue. Here we present a strategy to produce nanocomposites with highly ordered layered structures using shear-flow-induced alignment of two-dimensional nanosheets at an immiscible hydrogel/oil interface. For example, nanocomposites based on nanosheets of graphene oxide and clay exhibit a tensile strength of up to 1,215 ± 80 megapascals and a Young's modulus of 198.8 ± 6.5 gigapascals, which are 9.0 and 2.8 times higher, respectively, than those of natural nacre (mother of pearl). When nanosheets of clay are used, the toughness of the resulting nanocomposite can reach 36.7 ± 3.0 megajoules per cubic metre, which is 20.4 times higher than that of natural nacre; meanwhile, the tensile strength is 1,195 ± 60 megapascals. Quantitative analysis indicates that the well aligned nanosheets form a critical interphase, and this results in the observed mechanical properties. We consider that our strategy, which could be readily extended to align a variety of two-dimensional nanofillers, could be applied to a wide range of structural composites and lead to the development of high-performance composites.

Author Correction: Layered nanocomposites by shear-flow-induced alignment of nanosheets.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Hydroxide and Hydronium Ions Modulate the Dynamic Evolution of Nitrogen Nanobubbles in Water.

It has been widely recognized that the pH environment influences the nanobubble dynamics and hydroxide ions adsorbed on the surface may be responsible for the long-term survival of the nanobubbles. However, understanding the distribution of hydronium and hydroxide ions in the vicinity of a bulk nanobubble surface at a microscopic scale and the consequent impact of these ions on the nanobubble behavior remains a challenging endeavor. In this study, we carried out deep potential molecular dynamics simulations to explore the behavior of a nitrogen nanobubble under neutral, acidic, and alkaline conditions and the inherent mechanism, and we also conducted a theoretical thermodynamic and dynamic analysis to address constraints related to simulation duration. Our simulations and theoretical analyses demonstrate a trend of nanobubble dissolution similar to that observed experimentally, emphasizing the limited dissolution of bulk nanobubbles in alkaline conditions, where hydroxide ions tend to reside slightly farther from the nanobubble surface than hydronium ions, forming more stable hydrogen bond networks that shield the nanobubble from dissolution. In acidic conditions, the hydronium ions preferentially accumulating at the nanobubble surface in an orderly manner drive nanobubble dissolution to increase the entropy of the system, and the dissolved nitrogen molecules further strengthen the hydrogen bond networks of systems by providing a hydrophobic environment for hydronium ions, suggesting both entropy and enthalpy effects contribute to the instability of nanobubbles under acidic conditions. These results offer fresh insights into the double-layer distribution of hydroxide and hydronium near the nitrogen-water interface that influences the dynamic behavior of bulk nanobubbles.

Nanoporous Aramid Nanofiber Separators with High Modulus and Thermal Stability for Safe Lithium-Ion Batteries.

Developing high-safety separators is a promising strategy to prevent thermal runaway in lithium-ion batteries (LIBs), which stems from the low melting temperatures and inadequate modulus of commercial polyolefin separators. However, achieving high modulus and thermal stability, along with uniform nanopores in these separators, poses significant challenges. Herein, the study presents ultrathin nanoporous aramid nanofiber (ANF) separators with high modulus and excellent thermal stability, enhancing the safety of LIBs. These separators are produced using a microfluidic-based continuous printing strategy, where the flow thickness can be meticulously controlled at the micrometer scale. This method allows for the continuous fabrication of nanoporous ANF separators with thicknesses ranging from 1.6 ± 0.1 µm to 2.7 ± 0.1 µm. Thanks to the double-side solvent diffusion, the separators exhibit controllably uniform pore sizes with a narrow distribution, spanning from 40 ± 5 nm to 105 ± 9 nm, and a high modulus of 3.3 ± 0.5 GPa. These nanoporous ANF separators effectively inhibit lithium dendrite formation, resulting in a high-capacity retention rate for the LIBs (80% after 240 cycles). Most notably, their robust structural and mechanical stability at elevated temperatures significantly enhances LIB safety under transient thermal abuse conditions, thus addressing critical safety concerns associated with LIBs.

Superspreading-Based Fabrication of Thermostable Nanoporous Polyimide Membranes for High Safety Separators of Lithium-Ion Batteries.

The development of thermally stable separators is a promising approach to address the safety issues of lithium-ion batteries (LIBs) owing to the serious shrinkage of commercial polyolefin separators at elevated temperatures. However, achieving controlled nanopores with a uniform size distribution in thermostable polymeric separators and high electrochemical performance is still a great challenge. In this study, nanoporous polyimide (PI) membranes with excellent thermal stability as high-safety separators is developed for LIBs using a superspreading strategy. The superspreading of polyamic acid solutions enables the generation of thin and uniform liquid layers, facilitating the formation of thin PI membranes with controllable and uniform nanopores with narrow size distribution ranging from 121 ± 5 nm to 86 ± 6 nm. Such nanoporous PI membranes display excellent structural stability at elevated temperatures up to 300 °C for at least 1 h. LIBs assembled with nanoporous PI membranes as separators show high specific capacity and Coulombic efficiency and can work normally after transient treatment at a high temperature (150 °C for 20 min) and high ambient temperature, indicating their promising application as high-safety separators for rechargeable batteries.

Intramolecular and Water Mediated Tautomerism of Solvated Glycine.

Understanding tautomerism and characterizing solvent effects on the dynamic processes pose significant challenges. Using enhanced-sampling molecular dynamics based on state-of-the-art deep learning potentials, we investigated the tautomeric equilibria of glycine in water. We observed that the tautomerism between neutral and zwitterionic glycine can occur through both intramolecular and intermolecular proton transfers. The latter proceeds involving a contact anionic-glycine-hydronium ion pair or separate cationic-glycine-hydroxide ion pair. These pathways with comparable barriers contribute almost equally to the reaction flux.

The efficacy of Tai Chi for essential hypertension: A systematic review and meta-analysis.

AIM: We aimed to assess the impact of Tai Chi interventions on individuals with essential hypertension and to compare the effects of Tai Chi versus control in this population. BACKGROUND: Tai Chi has been extensively utilized in the prevention of essential hypertension. Nevertheless, there is a lack of consensus regarding its benefits for treating essential hypertension. DESIGN: A systematic review and meta-analysis was conducted. DATA SOURCES: We conducted a systematic literature search of the Medline, Scholar, Elsevier, Wiley Online Library, Chinese Academic Journal (CNKI) and Wanfang databases from January 2003 to August 2023. REVIEW METHODS: Using the methods of the Cochrane Collaboration Handbook, a meta-analysis was conducted to assess the collective impact of Tai Chi exercise in controlling hypertension. The primary outcomes measured included blood pressure and nitric oxide levels. RESULTS: The participants consisted of adults with an average age of 57.1 years who had hypertension (mean ± standard deviation systolic blood pressure at 148.2 ± 12.1 mmHg and diastolic blood pressure at 89.2 ± 8.3 mmHg). Individuals who practiced Tai Chi experienced reductions in systolic blood pressure of 10.6 mmHg, diastolic blood pressure of 4.7 mmHg and an increase in nitric oxide levels. CONCLUSIONS: Tai Chi can be a viable lifestyle intervention for managing hypertension. Greater promotion of Tai Chi by medical professionals could extend these benefits to a larger patient population.

Wettability-Regulated Synthesis of Metal-Organic Framework Array with Subnanochannels Enables Efficient Separation of Mono-/Multivalent Metal Ions.

Achieving efficient separation of mono-/multivalent metal ions is essential in various fields, yet it remains a significant challenge. In this work, a metal-organic framework (MOF) array with subnanochannels that exhibit high selectivity and ion permeability in the sieving of mono-/multivalent metal ion was developed. Specifically, we used confined interfacial reaction at room temperature to synthesis the MOF array inside the micrometer through-pores of a polyethylene terephthalate (PET) membrane. The location of the oil/water interface was regulated by adjusting the surface wettability of the PET membrane. By taking advantage of size sieving effect of the subnanochannels of MOF crystals, we were able to effectively separate monovalent metal ions from multivalent metal ions with selectivity reaching up to 3930±373 (e.g., Li+ /Zr4+ ). The fluxes of Li+ ions were observed to be as high as 1.97 mol h-1 m-2 . The MOF array-based membrane with subnanochannels that we have developed exhibits great promise for applications in wastewater treatment, lithium extraction from salt-lake brines, and other related fields.

C, F co-doping Ag/TiO2 with visible light photocatalytic performance toward degrading Rhodamine B.

The organic pollutants in industrial wastewater continuously endanger human health. Therefore, effective treatment of organic pollutants is very urgent. Photocatalytic degradation technology is an excellent solution to remove it. TiO2 photocatalysts are easy to prepare and have high catalytic activity, unfortunately, TiO2 only absorbs ultraviolet light limiting its utilization of visible light. In this study, a facile environmentally friendly synthesis of Ag-coated on micro-wrinkled TiO2-based catalysts in order to extend the absorption of Visible light. Firstly, a fluorinated titanium dioxide precursor was prepared by a one-step solvothermal method, and the precursor was calcined at high temperature in a nitrogen atmosphere to form a carbon dopant, and then a surface silver-deposited carbon/fluorine co-doped TiO2 photocatalyst C/F-Ag-TiO2 was prepared by a hydrothermal method The results showed that the Ag was coated on the wrinkled TiO2 layer and C/F-Ag-TiO2 photocatalyst was synthetized successfully. Benefit from the synergistic effect of doped carbon and fluorine atoms in combination with the quantum size effect of the surface silver nanoparticles, the band gap energy of C/F-Ag-TiO2 (2.56 eV) is obviously lower than anatase (3.2eV). The photocatalyst achieved an impressive degradation rate of 84.2% for Rhodamine B in 4 h, with a degradation rate constant of 0.367 h-1, which was 17 times higher than that of P25 under visible light. Therefore, the C/F-Ag-TiO2 composite is a promising candidate as a highly efficient photocatalyst for environmental remediation.

A Multi-Scale Recursive Attention Feature Fusion Network for Image Super-Resolution Reconstruction Algorithm.

In recent years, deep convolutional neural networks (CNNs) have made significant progress in single-image super-resolution (SISR) tasks. Despite their good performance, the single-image super-resolution task remains a challenging one due to problems with underutilization of feature information and loss of feature details. In this paper, a multi-scale recursive attention feature fusion network (MSRAFFN) is proposed for this purpose. The network consists of three parts: a shallow feature extraction module, a multi-scale recursive attention feature fusion module, and a reconstruction module. The shallow features of the image are first extracted by the shallow feature extraction module. Then, the feature information at different scales is extracted by the multi-scale recursive attention feature fusion network block (MSRAFFB) to enhance the channel features of the network through the attention mechanism and fully fuse the feature information at different scales in order to improve the network's performance. In addition, the image features at different levels are integrated through cross-layer connections using residual connections. Finally, in the reconstruction module, the upsampling capability of the deconvolution module is used to enlarge the image while extracting its high-frequency information in order to obtain a sharper high-resolution image and achieve a better visual effect. Through extensive experiments on a benchmark dataset, the proposed network model is shown to have better performance than other models in terms of both subjective visual effects and objective evaluation metrics.

Mixed Matrix Membrane with Penetrating Subnanochannels: A Versatile Nanofluidic Platform for Selective Metal Ion Conduction.

Biological ion channels penetrated through cell membrane form unique transport pathways for selective ionic conductance. Replicating the success of ion selectivity with mixed matrix membranes (MMMs) will enable new separation technologies but remains challenging. Herein, we report a soft substrate-assisted solution casting method to develop MMMs with penetrating subnanochannels for selective metal ion conduction. The MMMs are composed of penetrating Prussian white (PW) microcubes with subnanochannels in dense polyimide (PI) matrices, achieving selective monovalent metal ion conduction. The ion selectivity of K+ /Mg2+ is up to 14.0, and the ion conductance of K+ can reach 45.5 µS with the testing diameter of 5 mm, which can be further improved by increasing the testing area. Given the diversity of nanoporous materials and polymer matrices, we expect that the MMMs with penetrating subnanochannels could be developed into a versatile nanofluidic platform for various emerging applications.

Microfluidic Cell Trap Arrays for Single Hematopoietic Stem/Progenitor Cell Behavior Analysis.

Hematopoietic stem/progenitor cell (HSPC) mobilization from the bone marrow to the bloodstream is a required step for blood cell renewal, and HSPC motility is a clinically relevant standard for peripheral blood stem cell transplantation. Individual HSPCs exhibit considerable heterogeneity in motility behaviors, which are subject to complex intrinsic and extrinsic regulatory mechanisms. Motility-based cell sorting is then demanded to fulfill the study of such mechanism complexity. However, due to the HSPC heterogeneity and difficulty in monitoring cell motility, such a platform is still not available. With the recent development of microfluidics technology, motility-based monitoring, sorting, collecting, and analysis of HSPC behaviors are highly possible and achievable if fluid channels and structures are correctly engineered. Here, a new design of microfluidic arrays for single-cell trapping is presented, enabling high-throughput analysis of individual HSPC motility and behavior. Using these arrays, it is observed that HSPC motility is positively correlated with CD34 asymmetric inheritance and cell differentiation. Transcriptomic analysis of HSPCs sorted according to motility reveals changes in expression of genes associated with the regulation of stem-cell maintenance. Ultimately, this novel, physical cell-sorting system can facilitate the screening of HSPC mobilization compounds and the analysis of signals driving HSPC fate decisions.

Microfluidics-Based Single-Cell Protrusion Analysis for Screening Drugs Targeting Subcellular Mitochondrial Trafficking in Cancer Progression.

Cancer cell migration is often guided by cell protrusions, whose formation and activity involve subcellular localization of mitochondria. However, the role of subcellular mitochondrial trafficking during cell protrusion generation is not well-understood amidst a lack of quantitative data. Here, we present a high-throughput microfluidic platform that enables the quantitative, single-cell precision analysis of cell protrusion formation during cell migration that is regulated by subcellular mitochondrial trafficking. Gene expression profiling of the isolated cell protrusions suggested that mitochondria were found in high numbers within cell protrusions, a finding validated by mitochondrial staining. Quantitative analysis revealed that the formation of cell protrusions could be effectively suppressed by inhibiting subcellular mitochondrial trafficking. We further demonstrated that rapid screening of mitochondria-specific therapeutic drugs to evaluate their effects on cell protrusion formation with single-cell precision could be achieved in the microfluidic platform, which could have clinical utility in the development of new anticancer agents.

CRISPR-Cas12a Coupled with Platinum Nanoreporter for Visual Quantification of SNVs on a Volumetric Bar-Chart Chip.

Methods that can detect and quantify single nucleotide variations (SNVs)/single nucleotide polymorphisms (SNPs) are greatly needed in the bioanalytical measurement of gene mutations and polymorphisms. Herein a visual and instrument-free SNV quantification platform is developed. Platinum nanoparticles tethered to magnetic beads by single-stranded DNAs are designed as quantitative readout reporters for a CRISPR-Cas12a nucleic acid detection system. The integration of platinum nanoreporter and CRISPR-Cas system with a volumetric bar-chart chip realizes the volumetric quantification of nucleic acids. This platform enables quantification of multiple cancer mutations in pure DNA samples and mock cell-free DNA samples in serum, with allelic fractions as low as 0.01%. This platform could have great potential in the quantification of SNVs/SNPs as well as other types of nucleic acid targets at the point of care.

High-Throughput Isolation of Cell Protrusions with Single-Cell Precision for Profiling Subcellular Gene Expression.

Invading cancer cells extend cell protrusions, which guide cancer-cell migration and invasion, eventually leading to metastasis. The formation and activity of cell protrusions involve the localization of molecules and organelles at the cell front; however, it is challenging to precisely isolate these subcellular structures at the single-cell level for molecular analysis. Here, we describe a newly developed microfluidic platform capable of high-throughput isolation of cell protrusions at single-cell precision for profiling subcellular gene expression. Using this microfluidic platform, we demonstrate the efficient generation of uniform cell-protrusion arrays (more than 5000 cells with protrusions) for a series of cell types. We show precise isolation of cell protrusions with high purity at single-cell precision for subsequent RNA-Seq analysis, which was further validated by RT-qPCR and RNA FISH. Our highly controlled protrusion isolation method opens a new avenue for the study of subcellular functional mechanisms and signaling pathways in metastasis.

Herpes Simplex Virus 1 UL41 Protein Suppresses the IRE1/XBP1 Signal Pathway of the Unfolded Protein Response via Its RNase Activity.

During viral infection, accumulation of viral proteins can cause stress in the endoplasmic reticulum (ER) and trigger the unfolded protein response (UPR) to restore ER homeostasis. The inositol-requiring enzyme 1 (IRE1)-dependent pathway is the most conserved of the three UPR signal pathways. Upon activation, IRE1 splices out an intron from the unspliced inactive form of X box binding protein 1 [XBP1(u)] mRNA and produces a transcriptionally potent spliced form [XBP1(s)]. Previous studies have reported that the IRE1/XBP1 pathway is inhibited upon herpes simplex virus 1 (HSV-1) infection; however, the underlying molecular mechanism is still elusive. Here, we uncovered a role of the HSV-1 UL41 protein in inhibiting the IRE1/XBP1 signal pathway. Ectopic expression of UL41 decreased the expression of XBP1 and blocked XBP1 splicing activation induced by the ER stress inducer thapsigargin. Wild-type (WT) HSV-1, but not the UL41-null mutant HSV-1 (R2621), decreased XBP1 mRNA induced by thapsigargin. Nevertheless, infection with both WT HSV-1 and R2621 without drug pretreatment could reduce the mRNA and protein levels of XBP1(s), and additional mechanisms might contribute to this inhibition of XBP1(s) during R2621 infection. Taking these findings together, our results reveal XBP1 as a novel target of UL41 and provide insights into the mechanism by which HSV-1 modulates the IRE1/XBP1 pathway. IMPORTANCE: During viral infection, viruses hijack the host translation apparatus to produce large amounts of viral proteins, which leads to ER stress. To restore ER homeostasis, cells initiate the UPR to alleviate the effects of ER stress. The IRE1/XBP1 pathway is the most conserved UPR branch, and it activates ER-associated protein degradation (ERAD) to reduce the ER load. The IRE1/XBP1 branch is repressed during HSV-1 infection, but little is known about the underlying molecular mechanism. Our results show for the first time that UL41 suppresses the IRE1/XBP1 signal pathway by reducing the accumulation of XBP1 mRNA, and characterization of the underlying molecular mechanism provides new insight into the modulation of UPR by HSV-1.

Designing Bioinspired Anti-Biofouling Surfaces based on a Superwettability Strategy.

Anti-biofouling surfaces are of high importance owing to their crucial roles in biosensors, biomedical devices, food processing, the marine industry, etc. However, traditional anti-biofouling surfaces based on either the release of biocidal compounds or surface chemical/physical design cannot satisfy the practical demands when meeting real-world complex conditions. The outstanding performances of natural anti-biofouling surfaces motivate the development of new bioinspired anti-biofouling surfaces. Herein, a novel strategy is proposed for rationally designing bioinspired anti-biofouling surfaces based on superwettability. By utilizing the trapped air cushions or liquid layers, Lotus leaf inspired superhydrophobic surfaces, fish scales inspired underwater superoleophobic surfaces, and Nepenthes pitcher plants inspired omniphobic slippery surfaces have been successfully designed as anti-biofouling surfaces to effectively resist proteins, bacteria, cells, and marine organisms. It is believed that these novel superwettability-based anti-biofouling surfaces will bring a new era to both biomedical technology and the marine industry, and will greatly benefit human health and daily life in the near future.

Correction: Recent progress of abrasion-resistant materials: learning from nature.

Correction for 'Recent progress of abrasion-resistant materials: learning from nature' by Jingxin Meng et al., Chem. Soc. Rev., 2015, DOI: .

Recent progress of abrasion-resistant materials: learning from nature.

Abrasion-resistant materials have attracted great attention for their broad applications in industry, biomedicine and military. However, the development of abrasion-resistant materials that have with unique features such as being lightweight and flexible remains a great challenge in order to satisfy unmet demands. The outstanding performance of natural abrasion-resistant materials motivates the development of new bio-inspired abrasion-resistant materials. This review summarizes the recent progress in the investigation of natural abrasion-resistant materials to explore their general design principles (i.e., the correlation between chemical components and structural features). Following natural design principles, several artificial abrasion-resistant materials have shown unique abrasion-resistant properties. The potential challenges in the future and possible solutions for designing bio-inspired abrasion-resistant materials are also briefly discussed.