Airborne transmission of human-isolated avian H3N8 influenza virus between ferrets.

H3N8 avian influenza viruses (AIVs) in China caused two confirmed human infections in 2022, followed by a fatal case reported in 2023. H3N8 viruses are widespread in chicken flocks; however, the zoonotic features of H3N8 viruses are poorly understood. Here, we demonstrate that H3N8 viruses were able to infect and replicate efficiently in organotypic normal human bronchial epithelial (NHBE) cells and lung epithelial (Calu-3) cells. Human isolates of H3N8 virus were more virulent and caused severe pathology in mice and ferrets, relative to chicken isolates. Importantly, H3N8 virus isolated from a patient with severe pneumonia was transmissible between ferrets through respiratory droplets; it had acquired human-receptor-binding preference and amino acid substitution PB2-E627K necessary for airborne transmission. Human populations, even when vaccinated against human H3N2 virus, appear immunologically naive to emerging mammalian-adapted H3N8 AIVs and could be vulnerable to infection at epidemic or pandemic proportion.

Protection of blood-brain barrier by endothelial DAPK1 deletion after stroke.

Death-associated protein kinase (DAPK) 1 is a critical mediator for neuronal cell death in cerebral ischemia, but its role in blood-brain barrier (BBB) disruption is incompletely understood. Here, we found that endothelial-specific deletion of Dapk1 using Tie2 Cre protected the brain of Dapk1fl/fl mice against middle cerebral artery occlusion (MCAO), characterized by mitigated Evans blue dye (EBD) extravasation, reduced infarct size and improved behavior. In vitro experiments also indicated that DAPK1 deletion inhibited oxygen-glucose deprivation (OGD)-induced tight junction alteration between cerebral endothelial cells (CECs). Mechanistically, we revealed that DAPK1-DAPK3 interaction activated cytosolic phospholipase A2 (cPLA2) in OGD-stimulated CECs. Our results thus suggest that inhibition of endothelial DAPK1 specifically prevents BBB damage after stroke.

Benzothiadiazole-Based Ordered Mesoporous Polymer as a Versatile, Metal-Free Heterogeneous Photocatalyst.

Visible-light active heterogeneous organophotocatalysts have recently gained considerable interest in organic synthetic community. Ordered mesoporous polymers (OMPs) are highly promising as heterogeneous alternative to traditional precious metal/organic dyes-based photocatalysts. Herein, we report the preparation of a benzothiadiazole functionalized OMPs (BT-MPs) through a "bottom-up" strategy. High ordered periodic porosity, large surface area, excellent stability and rational energy-band structures guarantee the high catalytic activity of BT-MPs. As a result, at least six conversions, e.g., the [3+2] cycloaddition of phenols with olefins, the selective oxidation of sulfides, the C-3 thiocyanation of indole and the aminothiocyanation of ß-keto ester, could be promoted smoothly by BT-MPs. In addition, BT-MPs was readily recovered with well maintaining its photocatalytic activity and could be reused for at least eight times. This study highlights the potential of exploiting photoactive OMPs as recyclable, robust and metal-free heterogeneous photocatalysts.

[Pathogenic mechanisms of impaired neuronal autophagy flux after ischemic stroke].

Autophagy is a metabolic process in which damaged organelles, obsolete proteins, excess cytoplasmic components, and even pathogens are presented to lysosomes for degradation via autophagosomes. It includes 4 processes: the initiation of autophagy, the formation of autophagosomes, the fusion of autophagosomes with lysosomes, and the degradation and removal of autophagic substrates within autophagic lysosomes. When these processes are continuous, it is called autophagy flux. Blockage of one or certain steps in the autophagy/lysosome signaling pathway can lead to impaired autophagy flux. Numerous studies have shown that impaired autophagy flux is an important cause of neuronal damage in the ischemic penumbra after stroke. This paper summarized research progress in the pathological mechanisms that cause impaired neuronal autophagy flux after ischemic stroke and discusses methods to improve neuronal autophagy flux, in order to provide a reference for an in-depth investigation of the pathological injury mechanisms after stroke.

H9N2 virus-derived M1 protein promotes H5N6 virus release in mammalian cells: Mechanism of avian influenza virus inter-species infection in humans.

H5N6 highly pathogenic avian influenza virus (HPAIV) clade 2.3.4.4 not only exhibits unprecedented intercontinental spread in poultry, but can also cause serious infection in humans, posing a public health threat. Phylogenetic analyses show that 40% (8/20) of H5N6 viruses that infected humans carried H9N2 virus-derived internal genes. However, the precise contribution of H9N2 virus-derived internal genes to H5N6 virus infection in humans is unclear. Here, we report on the functional contribution of the H9N2 virus-derived matrix protein 1 (M1) to enhanced H5N6 virus replication capacity in mammalian cells. Unlike H5N1 virus-derived M1 protein, H9N2 virus-derived M1 protein showed high binding affinity for H5N6 hemagglutinin (HA) protein and increased viral progeny particle release in different mammalian cell lines. Human host factor, G protein subunit beta 1 (GNB1), exhibited strong binding to H9N2 virus-derived M1 protein to facilitate M1 transport to budding sites at the cell membrane. GNB1 knockdown inhibited the interaction between H9N2 virus-derived M1 and HA protein, and reduced influenza virus-like particles (VLPs) release. Our findings indicate that H9N2 virus-derived M1 protein promotes avian H5N6 influenza virus release from mammalian, in particular human cells, which could be a major viral factor for H5N6 virus cross-species infection.

Antifouling Slippery Surface against Marine Biofouling.

Titanium and its alloys have become the most excellent structure materials for naval seawater pipelines due to their high strength and good corrosion resistance. However, marine biofouling poses a serious threat to titanium alloy piping systems because of their good biocompatibility. Recently, the biomimetic antifouling coating, a novel antifouling method, has received great attention. Here, based on this biomimetic idea, we develop a nontoxic antifouling slippery surface (AFSS) using silicone oil, silane coupling agent, nanosilica, nanoceramic coating, epoxy resin, and capsaicin. The developed AFSS has excellent slippery performance for various droplets, good durability, and a superior self-cleaning property. Additionally, the antifouling performance of the AFSS was significantly enhanced, as confirmed by the reduced adhesion of proteins (70.7%), bacteria (97.2%), and algae (97.7%) compared to the ordinary titanium alloy. With these excellent properties, the AFSS was expected to be a promising candidate for protecting titanium alloy piping systems from marine biofouling.

Antiadhesion Superhydrophobic Bipolar Electrocoagulation Tweezers with High Conductivity and Stability.

Irregularly shaped electrosurgical devices face significant challenges in electrosurgery due to serious blood and tissue adhesion. Superhydrophobic surfaces inspired by lotus leaves have attracted great attention for their promising antiadhesion properties. However, there are few methods for efficiently preparing superhydrophobic irregularly shaped bipolar electrocoagulation tweezers (BETs). Herein, we propose a simple and environmentally friendly method to fabricate antiadhesion superhydrophobic surfaces on BETs. The superhydrophobicity is obtained by combining laser texturing to form rough structures and low surface energy modification via stearic acid. The formation mechanism of superhydrophobicity is investigated through analyzing microstructures and chemical compositions by scanning electron microscopy, white-light interferometry, and X-ray photoelectron spectroscopy. The functionalized BET surfaces exhibit excellent water repellency with a contact angle of 159.6°, a roll-off angle of 1°, and a surface energy of 14.3 mJ/m2, possessing excellent antiadhesion properties against blood, chicken breast tissue, and pork tissue. Compared with ordinary BETs, the mass of blood, pork tissue, and chicken breast tissue adhered to the superhydrophobic BET is reduced by 97.70, 70.34, and 75.35%, respectively. Moreover, the superhydrophobic BETs have excellent conductivity and maintain good antiadhesion properties after low-temperature storage for 2 weeks, after being impacted by sand and blood and 30 cycles of tape peeling tests. With outstanding antiadhesion performance, the superhydrophobic BET may have promising application prospects in the electrosurgery field.

Visible-light induced C(sp3)-H arylation of glycine derivatives by cerium catalysis.

A Ce(III)-catalyzed, visible-light induced aerobic oxidative dehydrogenative coupling reaction between glycine derivatives and electron-rich arenes is disclosed. The protocol proceeds efficiently under mild conditions, providing an efficient method for the rapid synthesis of α-arylglycine derivatives without the need for an external photosensitizer and additional oxidant. Moreover, this protocol could be performed on a 5 mmol scale, without obvious reduction of the efficiency.

Prevalent Eurasian avian-like H1N1 swine influenza virus with 2009 pandemic viral genes facilitating human infection.

Pigs are considered as important hosts or "mixing vessels" for the generation of pandemic influenza viruses. Systematic surveillance of influenza viruses in pigs is essential for early warning and preparedness for the next potential pandemic. Here, we report on an influenza virus surveillance of pigs from 2011 to 2018 in China, and identify a recently emerged genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 virus, which bears 2009 pandemic (pdm/09) and triple-reassortant (TR)-derived internal genes and has been predominant in swine populations since 2016. Similar to pdm/09 virus, G4 viruses bind to human-type receptors, produce much higher progeny virus in human airway epithelial cells, and show efficient infectivity and aerosol transmission in ferrets. Moreover, low antigenic cross-reactivity of human influenza vaccine strains with G4 reassortant EA H1N1 virus indicates that preexisting population immunity does not provide protection against G4 viruses. Further serological surveillance among occupational exposure population showed that 10.4% (35/338) of swine workers were positive for G4 EA H1N1 virus, especially for participants 18 y to 35 y old, who had 20.5% (9/44) seropositive rates, indicating that the predominant G4 EA H1N1 virus has acquired increased human infectivity. Such infectivity greatly enhances the opportunity for virus adaptation in humans and raises concerns for the possible generation of pandemic viruses.

Reassortment with dominant chicken H9N2 influenza virus contributed to the fifth H7N9 virus human epidemic.

H9N2 Avian influenza virus (AIV) is regarded as a principal donor of viral genes through reassortment to co-circulating influenza viruses that can result in zoonotic reassortants. Whether H9N2 virus can maintain sustained evolutionary impact on such reassortants is unclear. Since 2013, avian H7N9 virus had caused five sequential human epidemics in China; the fifth wave in 2016-2017 was by far the largest but the mechanistic explanation behind the scale of infection is not clear. Here, we found that, just prior to the fifth H7N9 virus epidemic, H9N2 viruses had phylogenetically mutated into new sub-clades, changed antigenicity and increased its prevalence in chickens vaccinated with existing H9N2 vaccines. In turn, the new H9N2 virus sub-clades of PB2 and PA genes, housing mammalian adaptive mutations, were reassorted into co-circulating H7N9 virus to create a novel dominant H7N9 virus genotype that was responsible for the fifth H7N9 virus epidemic. H9N2-derived PB2 and PA genes in H7N9 virus conferred enhanced polymerase activity in human cells at 33°C and 37°C, and increased viral replication in the upper and lower respiratory tracts of infected mice which could account for the sharp increase in human cases of H7N9 virus infection in the 2016-2017 epidemic. The role of H9N2 virus in the continual mutation of H7N9 virus highlights the public health significance of H9N2 virus in the generation of variant reassortants of increasing zoonotic potential.IMPORTANCEAvian H9N2 influenza virus, although primarily restricted to chicken populations, is a major threat to human public health by acting as a donor of variant viral genes through reassortment to co-circulating influenza viruses. We established that the high prevalence of evolving H9N2 virus in vaccinated flocks played a key role, as donor of new sub-clade PB2 and PA genes in the generation of a dominant H7N9 virus genotype (G72) with enhanced infectivity in humans during the 2016-2017 N7N9 virus epidemic. Our findings emphasize that the ongoing evolution of prevalent H9N2 virus in chickens is an important source, via reassortment, of mammalian adaptive genes for other influenza virus subtypes. Thus, close monitoring of prevalence and variants of H9N2 virus in chicken flocks is necessary in the detection of zoonotic mutations.

IL-37 blocks gouty inflammation by shaping macrophages into a non-inflammatory phagocytic phenotype.

OBJECTIVE: Interleukin (IL)-37 is a natural suppressor of inflammation. Macrophages play an important role in acute gout flare by dominating the inflammation and spontaneous relief. We have reported that IL-37 could limit runaway inflammation in gout. Here we focus on whether IL-37 inhibits gouty inflammation by altering macrophage functions, and how it does so. METHODS: Macrophage functions were evaluated in terms of phagocytosis, pyroptosis, polarization and metabolism. Phagocytosis and polarization of macrophages were detected by side scattering and double-labelling induced nitrogen monoxide synthase (iNOS)/arginase-1 (Arg-1) using flow cytometry, respectively. Transcription of pyroptosis-related molecules was detected by qPCR. Metabolomics was performed by liquid chromatograph mass spectrometer. Human IL-37 knock-in mice and a model with point mutation (S9A) at mouse Gsk3b locus were created by CRISPR/Cas-mediated genome engineering. MSU was injected into the paws and peritoneal cavity to model acute gout. Vernier calliper was used to measure the thickness of the paws. The mice paws and human synovium tissues or tophi were collected for pathological staining. Peritoneal fluid of mice was used to enrich macrophages to detect polarization. RESULTS: IL-37 promoted non-inflammatory phagocytic activity of macrophages by enhancing phagocytosis of MSU, reducing transcription of pyroptosis-related proteins and release of inflammatory cytokines, protecting mitochondrial function, and mediating metabolic reprogramming in MSU-treated THP-1 cells. These multifaceted roles of IL-37 were partly depended on the mediation of glycogen synthase kinase-3ß (GSK-3ß). CONCLUSIONS: Our study revealed that IL-37 could shape macrophages into a 'silent' non-inflammatory phagocytic fashion. IL-37 may become a potentially valuable treatment option for patients of chronic gout, especially for those with tophi.

Sound focusing by a broadband acoustic Luneburg lens.

The high-performance and aberration-free broadband acoustic lens holds promise for extensive applications, yet remains challenged. In this work, a scheme is proposed, and the experimental demonstration of a planar acoustic Luneburg lens capable of focusing broadband sound ranging from 1 to 3 kHz (relative bandwidth approaching to 100%) in an aberration-free manner is presented. Concretely, plane sound within the frequency range incident from one side can be concentrated on a same point on the opposite edge of the Luneburg lens. The demanded refractive indexes of the lens are obtained from the component space coil acoustic metamaterials, which can easily manipulate the refractive index by adjusting a structural parameter. The prototype of the proposed Luneburg lens is fabricated by three-dimensional printing technology and experimentally characterized in a two-dimensional acoustic measuring platform. The measured results are consistently in good agreement with those from the numerical simulations. Finally, the proposed Luneburg lens is employed to construct a wide-angle acoustic reflector, which can produce a strong echo propagating in the direction exactly opposite to the incident wave. These results facilitate potential possibilities for developing more acoustic functional devices capable of manipulating broadband sound.

A deep residual learning network for predicting lung adenocarcinoma manifesting as ground-glass nodule on CT images.

OBJECTIVE: To develop a deep learning-based artificial intelligence (AI) scheme for predicting the likelihood of the ground-glass nodule (GGN) detected on CT images being invasive adenocarcinoma (IA) and also compare the accuracy of this AI scheme with that of two radiologists. METHODS: First, we retrospectively collected 828 histopathologically confirmed GGNs of 644 patients from two centers. Among them, 209 GGNs are confirmed IA and 619 are non-IA, including 409 adenocarcinomas in situ and 210 minimally invasive adenocarcinomas. Second, we applied a series of pre-preprocessing techniques, such as image resampling, rescaling and cropping, and data augmentation, to process original CT images and generate new training and testing images. Third, we built an AI scheme based on a deep convolutional neural network by using a residual learning architecture and batch normalization technique. Finally, we conducted an observer study and compared the prediction performance of the AI scheme with that of two radiologists using an independent dataset with 102 GGNs. RESULTS: The new AI scheme yielded an area under the receiver operating characteristic curve (AUC) of 0.92 ± 0.03 in classifying between IA and non-IA GGNs, which is equivalent to the senior radiologist's performance (AUC 0.92 ± 0.03) and higher than the score of the junior radiologist (AUC 0.90 ± 0.03). The Kappa value of two sets of subjective prediction scores generated by two radiologists is 0.6. CONCLUSIONS: The study result demonstrates using an AI scheme to improve the performance in predicting IA, which can help improve the development of a more effective personalized cancer treatment paradigm. KEY POINTS: • The feasibility of using a deep learning method to predict the likelihood of the ground-glass nodule being invasive adenocarcinoma. • Residual learning-based CNN model improves the performance in classifying between IA and non-IA nodules. • Artificial intelligence (AI) scheme yields higher performance than radiologists in predicting invasive adenocarcinoma.

Energy conversion based on superhydrophobic surfaces.

Covering about 70% of the earth's surface, water contains considerable energy that remains unexploited. Superhydrophobic surfaces (SHSs) possess excellent water repellency, and energy conversion based on SHSs has opened up a new avenue for efficient collection and utilization of water energy. Therefore, it is of great significance to efficiently prepare SHSs and apply them for energy conversion in different fields. In this review, we first summarize the fabrication methods of SHSs, and then provide an overview of the energy conversion forms based on SHSs. Finally, the related applications corresponding to the energy conversion forms are introduced, including renewable energy collection and utilization, wearable device design, use of liquid sensors, surface cooling and heat dissipation, self-propelled devices, droplet manipulation and lab-on-a-chip devices; and their challenges and future perspectives are highlighted.

Prevailing I292V PB2 mutation in avian influenza H9N2 virus increases viral polymerase function and attenuates IFN-ß induction in human cells.

Adaptation of PB2 protein is important for the establishment of avian influenza viruses in mammalian hosts. Here, we identify I292V as the prevalent mutation in PB2 of circulating avian H9N2 and pandemic H1N1 viruses. The same dominant PB2 mutation is also found in most human isolates of emergent avian H7N9 and H10N8 viruses. In human cells, PB2-292V in H9N2 virus has the combined ability of conferring higher viral polymerase activity and stronger attenuation of IFN-ß induction than that of its predecessor PB2-292I. IFN-ß attenuation is accompanied by higher binding affinity of PB2-292V for host mitochondrial antiviral signalling protein, an important intermediary protein in the induction of IFN-ß. In the mouse in vivo model, PB2-292V mutation increases H9N2 virus replication with ensuing increase in disease severity. Collectively, PB2-292V is a new mammalian adaptive marker that promotes H9N2 virus replication in mammalian hosts with the potential to improve transmission from birds to humans.

Droplet Mechanical Hand Based on Anisotropic Water Adhesion of Hydrophobic-Superhydrophobic Patterned Surfaces.

Superhydrophobic copper surfaces patterned with non-round hydrophobic areas were fabricated by a combination of through-mask chemical oxidation and fluorocarbon film deposition techniques. The anisotropic sliding resistance of droplets on typical non-round hydrophobic patterns such as semicircle, V-shape, and line segment hydrophobic patterns was observed. The dependence of sliding anisotropy on the pattern shape and dimensions was investigated. Results showed that the experimental sliding resistance was in good agreement with the calculated data using a classical drag-resistance model (Furmidge equation). By taking advantage of the anisotropic sliding resistance, these patterned surfaces can be used as droplet mechanical hands to capture, transfer, mix, and release in situ micro droplets by simply moving the surfaces in different directions. A droplet pinned on a non-round hydrophobic pattern can be captured by lifting a surface with another non-round hydrophobic pattern in a large-sliding-resistance direction after touching it, while the captured droplet can be released in situ with nearly no mass loss by horizontally moving the surface in the low-sliding-resistance direction. The lossless droplet manipulations using hydrophobic/superhydrophobic patterned surfaces have advantages of being low in cost and easy to operate and may have great promising applications to high throughput drug screening, molecular detection, and other lab-on-chip devices.

3Cpro of foot-and-mouth disease virus antagonizes the interferon signaling pathway by blocking STAT1/STAT2 nuclear translocation.

UNLABELLED: Foot-and-mouth disease virus (FMDV) causes a highly contagious, debilitating disease in cloven-hoofed animals with devastating economic consequences. To survive in the host, FMDV has evolved to antagonize the host type I interferon (IFN) response. Previous studies have reported that the leader proteinase (L(pro)) and 3C(pro) of FMDV are involved in the inhibition of type I IFN production. However, whether the proteins of FMDV can inhibit type I IFN signaling is less well understood. In this study, we first found that 3C(pro) of FMDV functioned to interfere with the JAK-STAT signaling pathway. Expression of 3C(pro) significantly reduced the transcript levels of IFN-stimulated genes (ISGs) and IFN-stimulated response element (ISRE) promoter activity. The protein level, tyrosine phosphorylation of STAT1 and STAT2, and their heterodimerization were not affected. However, the nuclear translocation of STAT1/STAT2 was blocked by the 3C(pro) protein. Further mechanistic studies demonstrated that 3C(pro) induced proteasome- and caspase-independent protein degradation of karyopherin α1 (KPNA1), the nuclear localization signal receptor for tyrosine-phosphorylated STAT1, but not karyopherin α2, α3, or α4. Finally, we showed that the protease activity of 3C(pro) contributed to the degradation of KPNA1 and thus blocked STAT1/STAT2 nuclear translocation. Taken together, results of our experiments describe for the first time a novel mechanism by which FMDV evolves to inhibit IFN signaling and counteract host innate antiviral responses. IMPORTANCE: We show that 3C(pro) of FMDV antagonizes the JAK-STAT signaling pathway by blocking STAT1/STAT2 nuclear translocation. Furthermore, 3C(pro) induces KPNA1 degradation, which is independent of proteasome and caspase pathways. The protease activity of 3C(pro) contributes to the degradation of KPNA1 and governs the ability of 3C(pro) to inhibit the JAK-STAT signaling pathway. This study uncovers a novel mechanism evolved by FMDV to antagonize host innate immune responses.

Influence of Fibre Orientation on the Slotting Quality of CFRP Composites Using the Multi-Tooth Mill.

Carbon fibre-reinforced plastic (CFRP) composites, prized for their exceptional properties, often encounter surface quality issues during slotting due to their inherent heterogeneity. This paper tackles CFRP slotting challenges by employing multi-tooth mills in experiments with various fibre orientations and tool feed rates. In-plane scratching tests are performed under linearly varying loads; then, slotting experiments are conducted at different parameters. The scratching test results indicate that the fibre orientation and cutting angles have significant influences on forces and fracture process. The slotting experiments demonstrate that cutting forces and surface roughness Sa of the bottom slotting surface are notably affected by the fibre orientation, with disparities between up-milling and down-milling sides. Reorganising Sa data by local fibre cutting angle θ highlights consistent Sa variations between up-milling and down-milling sides for 0° ≤ θ ≤ 90°, with lower Sa on the up-milling side. However, for 90° < θ ≤ 150°, Sa variations diverge, with lower Sa on the down-milling side. Unexpectedly, Sa on the down-milling side decreases with increasing θ in this range. Additionally, the tool feed rate exerts a more pronounced influence on Sa on the up-milling side.

Elastic Droplet-Based Magnetoelectric Generator for High-performance Energy Collection.

Conventional magnetoelectric generators are regarded as effective devices for harvesting concentrated hydraulic power but are ineffective for dispersed hydropower (e.g., raindrops) due to their bulkiness and immobility. Here, we propose a superhydrophobic magnetoelectric generator (MSMEG) based on an elastic magnetic film that can efficiently convert the energy of lightweight water droplets into electricity. The MSMEG consists of five parts: a superhydrophobic magnetic material-based film (SMMF), a coil, a NdFeB magnet, an acrylic housing, and an expandable polystyrene (EPS) base. The SMMF with coil can deform/recover when droplets impact/leave the MSMEG, resulting in a peak current, peak charge density, and peak power density of ∼13.02 mA, ∼1826.5 mC/m2, and ∼1413.0 mW/m2, respectively, with a load resistance of 47 Ω. Related working mechanism is analyzed through Maxwell numerical simulation, which is used for further guidance on increasing the electrical output of the MSMEG. Furthermore, the MSMEG can quickly charge a commercial capacitor with 2.7 V/1 F to 1.18 V within 200 s and power diverse electronic devices (e.g., light emitting diodes (LEDs), fans) with constant excitation by water droplets. We believe that such an MSMEG is expected to provide a promising strategy for efficiently harvesting dispersed raindrop energy.

Visible-light-induced Csp3-H functionalization of glycine derivatives by cerium catalysis.

A Ce(III)-catalyzed, visible-light-induced aerobic oxidative dehydrogenative coupling/aromatization reaction between glycine derivatives and alkenes has been developed, which provides an efficient approach for the synthesis of quinoline derivatives and post-modification of oligopeptides containing glycine residues under mild conditions without the need for external photosensitizers.