Strong Covalent Coupling in Vertically Layered SnSe2/PTAA Heterojunctions Enabled High Performance Inorganic-Organic Hybrid Photodetectors.

Controllable large-scale integration of two-dimensional (2D) materials with organic semiconductors and the realization of strong coupling between them still remain challenging. Herein, we demonstrate a wafer-scale, vertically layered SnSe2/PTAA heterojunction array with high light-trapping ability via a low-temperature molecular beam epitaxy method and a facile spin-coating process. Conductive probe atomic force microscopy (CP-AFM) measurements reveal strong rectification and photoresponse behavior in the individual SnSe2 nanosheet/PTAA heterojunction. Theoretical analysis demonstrates that vertically layered SnSe2/PTAA heterojunctions exhibit stronger C-Se covalent coupling than that of the conventional tiled type, which could facilitate more efficient charge transfer. Benefiting from these advantages, the SnSe2/PTAA heterojunction photodetectors with an optimized PTAA concentration show high performance, including a responsivity of 41.02 A/W, an external quantum efficiency of 1.31 × 104%, and high uniformity. The proposed approach for constructing large-scale 2D inorganic-organic heterostructures represents an effective route to fabricate high-performance broadband photodetectors for integrated optoelectronic systems.

Fully Conjugated Covalent Organic Framework Nanosheets for Visible-Light-Driven Organic Synthesis in Water.

Covalent organic framework (COF) nanosheets have recently garnered great attention as a new class of functional materials. As one of the sustainable processes, however, the photocatalytic organic synthesis in water has not been investigated using COF nanosheets as a photocatalyst to date. Herein, we reported the synthesis of a fully conjugated COF nanosheets with carboxyl functional group through a cooperative strategy of chemical exfoliation and group transformation. The new COF nanosheets was found to be an efficient heterogeneous photocatalyst for a wide range of organic synthesis including selective oxidation of sulfides and oxidative coupling of benzylamines in water under visible-light illumination. This work contributes a new roadmap for the design and synthesis of functional COF-based nanosheets, but also further extends the application boundary of the ultrathin COF nanosheets.

2-Pyran-4-Ylidene Malononitrile Based Conjugated Microporous Polymers as Metal-Free Heterogeneous Photocatalysts for Organic Synthesis.

Photoactive conjugated microporous polymers (CMPs) as heterogeneous photocatalysts provide a sustainable alternative to classical metal-based semiconductor photosensitizers. However, previously reported CMPs are typically synthesized through metal catalyzed coupling reactions, which bears product separation, but also increases the price of materials. Herein, a new type of sp2 carbon linked DCM-CMPs are successfully designed and synthesized by organic base catalyzed Knoevenagel reaction using 2,6-Dimethyl-4H-pyran-4-ylidene-malononitrile and aromatic polyaldehydes as monomers. The new polymers feature inherent porosity, excellent stability, and fully π-conjugated skeleton with broad visible-light absorption. They effectively induce the synthesis of benzimidazole compounds under light irradiation, and exhibit wide substrate adaptability with outstanding recyclability.

Type-II IFN inhibits SARS-CoV-2 replication in human lung epithelial cells and ex vivo human lung tissues through indoleamine 2,3-dioxygenase-mediated pathways.

Interferons (IFNs) are critical for immune defense against pathogens. While type-I and -III IFNs have been reported to inhibit SARS-CoV-2 replication, the antiviral effect and mechanism of type-II IFN against SARS-CoV-2 remain largely unknown. Here, we evaluate the antiviral activity of type-II IFN (IFNγ) using human lung epithelial cells (Calu3) and ex vivo human lung tissues. In this study, we found that IFNγ suppresses SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues. Moreover, IFNγ treatment does not significantly modulate the expression of SARS-CoV-2 entry-related factors and induces a similar level of pro-inflammatory response in human lung tissues when compared with IFNß treatment. Mechanistically, we show that overexpression of indoleamine 2,3-dioxygenase 1 (IDO1), which is most profoundly induced by IFNγ, substantially restricts the replication of ancestral SARS-CoV-2 and the Alpha and Delta variants. Meanwhile, loss-of-function study reveals that IDO1 knockdown restores SARS-CoV-2 replication restricted by IFNγ in Calu3 cells. We further found that the treatment of l-tryptophan, a substrate of IDO1, partially rescues the IFNγ-mediated inhibitory effect on SARS-CoV-2 replication in both Calu3 cells and ex vivo human lung tissues. Collectively, these results suggest that type-II IFN potently inhibits SARS-CoV-2 replication through IDO1-mediated antiviral response.

Process-specified emission factors and characteristics of VOCs from the auto-repair painting industry.

Daily use of passenger vehicles leads to considerable emission of volatile organic compounds (VOCs), which are key precursors to the ground-level ozone pollution. While evaporative and tailpipe emission of VOCs from the passenger vehicles can be eliminated largely, or even completely, by electrification, VOCs emission from the use of coatings in auto-repair is unavoidable and has long been ignored. Here, we present for the first time, to the best of our knowledge, a comprehensive investigation on the emission factors and process-specified characteristics of VOCs from auto-repair painting, based on field measurements over 15 representative auto-repair workshops in the Pearl-River-Delta area, China. Replacement of solvent-borne coatings with water-borne counterparts, which was only achieved partially in the Basecoat step but not in the Putty, Primer and Clearcoat steps, could reduce the per automobile VOCs emission from 756.5 to 489.6 g and the per automobile ozone formation potential (OFP) from 2776.5 to 1666.4 g. Implementation of exhaust after-treatment led to a further reduction of the per automobile VOCs emission to 340.9 g, which is still ca. 42% higher than that from the state-of-art painting processes for the manufacture of passenger vehicles. According to the analysis of VOCs compositions, the Putty process was dominated by the emission of styrene, while Primer, Basecoat (solvent-borne) and Clearcoat steps were all characterized by the emission of n-butyl acetate and xylenes. By contrast, water-borne Basecoat step showed a prominent emission of n-amyl alcohol. Notably, for the full painting process to repair an automobile, n-butyl acetate emerged as the most abundant species in the VOCs emission, whereas xylenes contributed most significantly to the OFP. Scenario analysis suggested that reducing VOCs contents in the coatings, as well as improving the after-treatment efficiency, were highly potential solutions for effective reduction of VOCs emission from auto-repair. Our study contributes to an update of industrial inventories of VOCs emission, and may provide valuable insights for reducing VOCs emission and OFPs from the auto-repair industry.

Ecological Risk and Pollution Assessment of Heavy Metals in Farmland Soil Profile with Consideration of Atmosphere Deposition in Central China.

Heavy metals (HMs) in agricultural land have caused serious environmental problems, resulting in severe contamination of the food chain and posing potential health threats. This study aims to investigate the pollution levels and potential ecological risks of HMs in farmland soils in central China, taking into account atmospheric deposition. Several indices were used to assess the status of HMs and compare surface soil with deeper soil. Descriptive statistics, Pearson correlation, and UMAP clustering methods were utilized to identify the characteristics of HMs. Additionally, stepwise linear regression models were employed to quantify the contributions of different variables to the potential ecological risks of HMs. The results showed that the average content of Zn in surface soil (289.41 ± 87.72 mg/kg) was higher than in the deeper soil (207.62 ± 37.81 mg/kg), and similar differences were observed in the mean values of related Igeo (1.622 ± 0.453 in surface soil and 1.183 ± 0.259 in deeper soil) and PEI (0.965 ± 0.292 in surface soil and 0.692 ± 0.126 in deeper soil) indices. This indicates that surface soil is more heavily polluted. The UMAP results confirmed the high variability of HMs in the surface soil, while PCA results suggested the importance of pollution and ecological risk indices. The stepwise linear model revealed that different variable structures contribute differently to the risk. In conclusion, Cr and Zn were found to be the major contaminants in the local farmland soil, with higher concentrations in the surface soil. The geoaccumulation and total potential ecological risk were classified as low risk. High variability of HMs was observed in the surface soil. Therefore, HM-related pollution indices and ecological risk indices are important for assessing the contamination status of local HMs. The local potential ecological risk can be attributed to specific heavy metals, each of which can have different effects on the local ecological risk.

Divergent trajectory of replication and intrinsic pathogenicity of SARS-CoV-2 Omicron post-BA.2/5 subvariants in the upper and lower respiratory tract.

BACKGROUND: Earlier Omicron subvariants including BA.1, BA.2, and BA.5 emerged in waves, with a subvariant replacing the previous one every few months. More recently, the post-BA.2/5 subvariants have acquired convergent substitutions in spike that facilitated their escape from humoral immunity and gained ACE2 binding capacity. However, the intrinsic pathogenicity and replication fitness of the evaluated post-BA.2/5 subvariants are not fully understood. METHODS: We systemically investigated the replication fitness and intrinsic pathogenicity of representative post-BA.2/5 subvariants (BL.1, BQ.1, BQ.1.1, XBB.1, CH.1.1, and XBB.1.5) in weanling (3-4 weeks), adult (8-10 weeks), and aged (10-12 months) mice. In addition, to better model Omicron replication in the human nasal epithelium, we further investigated the replication capacity of the post-BA.2/5 subvariants in human primary nasal epithelial cells. FINDINGS: We found that the evaluated post-BA.2/5 subvariants are consistently attenuated in mouse lungs but not in nasal turbinates when compared with their ancestral subvariants BA.2/5. Further investigations in primary human nasal epithelial cells revealed a gained replication fitness of XBB.1 and XBB.1.5 when compared to BA.2 and BA.5.2. INTERPRETATION: Our study revealed that the post-BA.2/5 subvariants are attenuated in lungs while increased in replication fitness in the nasal epithelium, indicating rapid adaptation of the circulating Omicron subvariants in the human populations. FUNDING: The full list of funding can be found at the Acknowledgements section.

Correction: Nie et al. Endoplasmic Reticulum Stress Mediated NLRP3 Inflammasome Activation and Pyroptosis in THP-1 Macrophages Infected with Bacillus Calmette-Guérin. Int. J. Mol. Sci. 2023, 24, 11692.

Lei Liu was not included as an author in the original publication [...].

GSK2656157, a PERK Inhibitor, Alleviates Pyroptosis of Macrophages Induced by Mycobacterium Bacillus Calmette-Guerin Infection.

Tuberculosis (TB) is the leading cause of human death worldwide due to Mycobacterium tuberculosis (Mtb) infection. Mtb infection can cause macrophage pyroptosis. PERK, as a signaling pathway protein on the endoplasmic reticulum, plays an important role in infectious diseases. It is not clear whether PERK is involved in the regulation of pyroptosis of macrophages during Mtb infection. In this study, Bacillus Calmette-Guerin (BCG) infection resulted in high expression of pro-caspase-1, caspase-1 p20, GSDMD-N, and p-PERK in the THP-1 macrophage, being downregulated with the pre-treatment of GSK2656157, a PERK inhibitor. In addition, GSK2656157 inhibited the secretion of IL-1ß and IL-18, cell content release, and cell membrane rupture, as well as the decline in cell viability induced by BCG infection. Similarly, GSK2656157 treatment downregulated the expressions of pro-caspase-1, caspase-1 p20, caspase-11, IL-1ß p17, IL-18 p22, GSDMD, GSDMD-N, and p-PERK, as well as reducing fibrous tissue hyperplasia, inflammatory infiltration, and the bacterial load in the lung tissue of C57BL/6J mice infected with BCG. In conclusion, the inhibition of PERK alleviated pyroptosis induced by BCG infection, which has an effect of resisting infection.

Capping layer enabled controlled fragmentation of two-dimensional materials by cold drawing.

Cold drawing, a well-established processing technique in the polymer industry, was recently revisited and discovered as an efficient material structuring method to create ordered patterns in composites consisting of both cold-drawable polymers and brittle target materials. Such a high-yield and low-cost manufacturing technique enables the large-scale fabrication of micro-ribbon structures for a wide range of functional materials, including two-dimensional (2D) layered materials. Compared to the abundant phenomenological results from experiments, however, the underlying mechanisms of this technique are not fully explored. Here, supported by experimental investigation, finite element calculations, and theoretical modeling, we systematically study the effect of a capping layer on the controlled fragmentation of 2D materials deposited on polymer substrates during the cold drawing. The capping layer is found to prevent the premature fracture of the 2D thin films during elastic deformation of the substrate, when a specific requirement proposed by the theoretical model is satisfied. Controlled fragmentation is enabled in the necking stage due to the protective effect of the capping layer, which also influences the size of the resulting fragments. Flexible and stretchable electrodes based on 2D material ribbons are fabricated to demonstrate the effectiveness of the proposed roadmap. This study gives an accurate understanding of interactions between 2D materials, polymer substrates, and capping layers during cold drawing, and offers guidance for potential applications such as flexible electronics.

Recent progress of molybdenum carbide based electrocatalysts for electrocatalytic hydrogen evolution reaction.

Electrocatalytic hydrogen evolution reaction (HER) is one of the most promising and clean strategies to prepare hydrogen on a large scale. Nevertheless, the efficiency of HER is greatly restricted by the large overpotential at the anode, and it is necessary to develop low cost electrocatalysts with excellent performance and stability. Molybdenum carbide has shown great potential in the field of HER due to its unique electronic structure and physical and chemical properties. In this paper, the current progress of molybdenum carbide-based catalysts for HER is summarized. The influence of phase structure, nanostructure, heterostructure and heteroatoms doping on its catalytic performance is discussed in detail. Especially, the catalytic mechanisms are analyzed according to structural characterization and theoretical calculation results. Finally, the challenges and prospects for the further development of molybdenum carbide-based catalysts for HER are put forward to guide the progress of this field.

S100A4 Promotes BCG-Induced Pyroptosis of Macrophages by Activating the NF-κB/NLRP3 Inflammasome Signaling Pathway.

Pyroptosis is a host immune strategy to defend against Mycobacterium tuberculosis (Mtb) infection. S100A4, a calcium-binding protein that plays an important role in promoting cancer progression as well as the pathophysiological development of various non-tumor diseases, has not been explored in Mtb-infected hosts. In this study, transcriptome analysis of the peripheral blood of patients with pulmonary tuberculosis (PTB) revealed that S100A4 and GSDMD were significantly up-regulated in PTB patients' peripheral blood. Furthermore, there was a positive correlation between the expression of GSDMD and S100A4. KEGG pathway enrichment analysis showed that differentially expressed genes between PTB patients and healthy controls were significantly related to inflammation, such as the NOD-like receptor signaling pathway and NF-κB signaling pathway. To investigate the regulatory effects of S100A4 on macrophage pyroptosis, THP-1 macrophages infected with Bacillus Calmette-Guérin (BCG) were pre-treated with exogenous S100A4, S100A4 inhibitor or si-S100A4. This research study has shown that S100A4 promotes the pyroptosis of THP-1 macrophages caused by BCG infection and activates NLRP3 inflammasome and NF-κB signaling pathways, which can be inhibited by knockdown or inhibition of S100A4. In addition, inhibition of NF-κB or NLRP3 blocks the promotion effect of S100A4 on BCG-induced pyroptosis of THP-1 macrophages. In conclusion, S100A4 activates the NF-κB/NLRP3 inflammasome signaling pathway to promote macrophage pyroptosis induced by Mtb infection. These data provide new insights into how S100A4 affects Mtb-induced macrophage pyroptosis.

The viral fitness and intrinsic pathogenicity of dominant SARS-CoV-2 Omicron sublineages BA.1, BA.2, and BA.5.

BACKGROUND: Among the Omicron sublineages that have emerged, BA.1, BA.2, BA.5, and their related sublineages have resulted in the largest number of infections. While recent studies demonstrated that all Omicron sublineages robustly escape neutralizing antibody response, it remains unclear on whether these Omicron sublineages share any pattern of evolutionary trajectory on their replication efficiency and intrinsic pathogenicity along the respiratory tract. METHODS: We compared the virological features, replication capacity of dominant Omicron sublineages BA.1, BA.2 and BA.5 in the human nasal epithelium, and characterized their pathogenicity in K18-hACE2, A129, young C57BL/6, and aged C57BL/6 mice. FINDINGS: We found that BA.5 replicated most robustly, followed by BA.2 and BA.1, in the differentiated human nasal epithelium. Consistently, BA.5 infection resulted in higher viral gene copies, infectious viral titres and more abundant viral antigen expression in the nasal turbinates of the infected K18-hACE2 transgenic mice. In contrast, the Omicron sublineages are continuously attenuated in lungs of infected K18-hACE2 and C57BL/6 mice, leading to decreased pathogenicity. Nevertheless, lung manifestations remain severe in Omicron sublineages-infected A129 and aged C57BL/6 mice. INTERPRETATION: Our results suggested that the Omicron sublineages might be gaining intrinsic replication fitness in the upper respiratory tract, therefore highlighting the importance of global surveillance of the emergence of hyper-transmissive Omicron sublineages. On the contrary, replication and intrinsic pathogenicity of Omicron is suggested to be further attenuated in the lower respiratory tract. Effective vaccination and other precautions should be in place to prevent severe infections in the immunocompromised populations at risk. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Endoplasmic Reticulum Stress Mediated NLRP3 Inflammasome Activation and Pyroptosis in THP-1 Macrophages Infected with Bacillus Calmette-Guérin.

Tuberculosis (TB) is a zoonotic infectious disease caused by Mycobacterium tuberculosis (Mtb). Mtb is a typical intracellular parasite, and macrophages are its main host cells. NLRP3 inflammasome-mediated pyroptosis is a form of programmed cell death implicated in the clearance of pathogenic infections. The bidirectional regulatory effect of endoplasmic reticulum stress (ERS) plays a crucial role in determining cell survival and death. Whether ERS is involved in macrophage pyroptosis with Mtb infection remains unclear. This article aims to explore the regulation of the NLRP3 inflammasome and pyroptosis by ERS in THP-1 macrophages infected with Mycobacterium bovis Bacillus Calmette-Guérin (BCG). The results showed that BCG infection induced THP-1 macrophage ERS, NLRP3 inflammasome activation and pyroptosis, which was inhibited by ERS inhibitor TUDCA. NLRP3 inhibitor MCC950 inhibited THP-1 macrophage NLRP3 inflammasome activation and pyroptosis caused by BCG infection. Compared with specific Caspase-1 inhibitor VX-765, pan-Caspase inhibitor Z-VAD-FMK showed a more significant inhibitory effect on BCG infection-induced pyroptosis of THP-1 macrophages. Taken together, this study demonstrates that ERS mediated NLRP3 inflammasome activation and pyroptosis after BCG infection of THP-1 macrophages, and that BCG infection of THP-1 macrophages induces pyroptosis through canonical and noncanonical pathways.

Determination of beef tenderness based on airflow pressure combined with structural light three-dimensional (3D) vision technology.

The main factor affecting beef quality, consumer satisfaction, and purchase decisions is beef tenderness. In this study, a rapid nondestructive testing method for beef tenderness based on airflow pressure combined with structural light 3D vision technology was proposed. The structural light 3D camera was used to scan the 3D point cloud deformation information of the beef surface after the airflow acted on it for 1.8 s. Six deformation characteristics and three point cloud characteristics of the beef surface depression region were obtained by using denoising, point cloud rotation, point cloud segmentation, point cloud descending sampling, alphaShape, and other algorithms. A total of nine characteristics were mainly concentrated in the first five principal components (PCs). Therefore, the first five PCs were put into three different models. The results showed that the Extreme Learning Machine (ELM) model had a comparatively higher prediction effect for the prediction of beef shear force, with a root mean square error of prediction (RMSEP) of 11.1389 and a correlation coefficient (R) of 0.8356. In addition, the correct classification accuracy of the ELM model for tender beef achieved 92.96%. The overall classification accuracy reached 93.33%. Consequently, the proposed methods and technology can be applied for beef tenderness detection.

HPnet: Hybrid Parallel Network for Human Pose Estimation.

Hybrid models which combine the convolution and transformer model achieve impressive performance on human pose estimation. However, the existing hybrid models on human pose estimation, which typically stack self-attention modules after convolution, are prone to mutual conflict. The mutual conflict enforces one type of module to dominate over these hybrid sequential models. Consequently, the performance of higher-precision keypoints localization is not consistent with overall performance. To alleviate this mutual conflict, we developed a hybrid parallel network by parallelizing the self-attention modules and the convolution modules, which conduce to leverage the complementary capabilities effectively. The parallel network ensures that the self-attention branch tends to model the long-range dependency to enhance the semantic representation, whereas the local sensitivity of the convolution branch contributes to high-precision localization simultaneously. To further mitigate the conflict, we proposed a cross-branches attention module to gate the features generated by both branches along the channel dimension. The hybrid parallel network achieves 75.6% and 75.4%AP on COCO validation and test-dev sets and achieves consistent performance on both higher-precision localization and overall performance. The experiments show that our hybrid parallel network is on par with the state-of-the-art human pose estimation models.

A new generation Mpro inhibitor with potent activity against SARS-CoV-2 Omicron variants.

Emerging SARS-CoV-2 variants, particularly the Omicron variant and its sublineages, continually threaten the global public health. Small molecule antivirals are an effective treatment strategy to fight against the virus. However, the first-generation antivirals either show limited clinical efficacy and/or have some defects in pharmacokinetic (PK) properties. Moreover, with increased use of these drugs across the globe, they face great pressure of drug resistance. We herein present the discovery and characterization of a new generation antiviral drug candidate (SY110), which is a potent and selective inhibitor of SARS-CoV-2 main protease (Mpro). This compound displayed potent in vitro antiviral activity against not only the predominant SARS-CoV-2 Omicron sublineage BA.5, but also other highly pathogenic human coronaviruses including SARS-CoV-1 and MERS-CoV. In the Omicron-infected K18-hACE2 mouse model, oral treatment with SY110 significantly lowered the viral burdens in lung and alleviated the virus-induced pathology. Importantly, SY110 possesses favorable PK properties with high oral drug exposure and oral bioavailability, and also an outstanding safety profile. Furthermore, SY110 exhibited sensitivity to several drug-resistance Mpro mutations. Collectively, this investigation provides a promising new drug candidate against Omicron and other variants of SARS-CoV-2.

Altered host protease determinants for SARS-CoV-2 Omicron.

Successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requires proteolytic cleavage of the viral spike protein. While the role of the host transmembrane protease serine 2 in SARS-CoV-2 infection is widely recognized, the involvement of other proteases capable of facilitating SARS-CoV-2 entry remains incompletely explored. Here, we show that multiple members from the membrane-type matrix metalloproteinase (MT-MMP) and a disintegrin and metalloproteinase families can mediate SARS-CoV-2 entry. Inhibition of MT-MMPs significantly reduces SARS-CoV-2 replication in vitro and in vivo. Mechanistically, we show that MT-MMPs can cleave SARS-CoV-2 spike and angiotensin-converting enzyme 2 and facilitate spike-mediated fusion. We further demonstrate that Omicron BA.1 has an increased efficiency on MT-MMP usage, while an altered efficiency on transmembrane serine protease usage for virus entry compared with that of ancestral SARS-CoV-2. These results reveal additional protease determinants for SARS-CoV-2 infection and enhance our understanding on the biology of coronavirus entry.