Alkaline Modified Mesoporous Silica Supported Ruthenium Catalyst for Improved α-Amino Acid Synthesis.

Amino acids are a class of compounds with wide-ranging applications. The synthesis of amino acids from biomass-derived α-keto acids and ammonia is a sustainable way but the unstable primary imine intermediates (R-C=NH) easily form oligomers. Herein, targeting this problem, alkaline modified mesoporous silica was employed as a support for ruthenium (Ru/M-MCM-41), which could be used as a bifunctional catalyst in the reductive amination of α-keto acids to synthesize α-amino acids. The incorporation of Sr improved the dispersion of Ru nanoparticles and enhanced metal-support interactions via electron transfer from Sr to Ru, and the active Ru sites could efficiently hydrogenate primary imine intermediates to α-amino acids, thus prohibiting the formation of oligomers. Moreover, the Sr-dopant introduces base sites that could catalyze the hydrolysis of oligomers back to primary imine intermediates and finally hydrogenated to α-amino acids. As a result, >99% yield of glycine was achieved from glyoxylic acid over Ru/Sr-MCM-41, which is nearly three times that achieved over Ru/MCM-41 (32.2%).

Conditional reprogrammed human limbal epithelial cell model for anti-SARS-CoV-2 drug screening.

To minimize the global pandemic COVID-19 spread, understanding the possible transmission routes of SARS-CoV-2 and discovery of novel antiviral drugs are necessary. We describe here that the virus can infect ocular surface limbal epithelial, but not other regions. Limbal supports wild type and mutant SARS-CoV-2 entry and replication depending on ACE2, TMPRSS2 and possibly other receptors, resulting in slight CPE and arising IL-6 secretion, which symbolizes conjunctivitis in clinical symptoms. With this limbal model, we have screened two natural product libraries and discovered several unreported drugs. Our data reveal important commonalities between COVID-19 and ocular infection with SARS-CoV-2, and establish an ideal cell model for drug screening and mechanism research.

Photoacoustic Tomography with Temporal Encoding Reconstruction (PATTERN) for cross-modal individual analysis of the whole brain.

Cross-modal analysis of the same whole brain is an ideal strategy to uncover brain function and dysfunction. However, it remains challenging due to the slow speed and destructiveness of traditional whole-brain optical imaging techniques. Here we develop a new platform, termed Photoacoustic Tomography with Temporal Encoding Reconstruction (PATTERN), for non-destructive, high-speed, 3D imaging of ex vivo rodent, ferret, and non-human primate brains. Using an optimally designed image acquisition scheme and an accompanying machine-learning algorithm, PATTERN extracts signals of genetically-encoded probes from photobleaching-based temporal modulation and enables reliable visualization of neural projection in the whole central nervous system with 3D isotropic resolution. Without structural and biological perturbation to the sample, PATTERN can be combined with other whole-brain imaging modalities to acquire the whole-brain image with both high resolution and morphological fidelity. Furthermore, cross-modal transcriptome analysis of an individual brain is achieved by PATTERN imaging. Together, PATTERN provides a compatible and versatile strategy for brain-wide cross-modal analysis at the individual level.

High-efficient separation of deoxyribonucleic acid from pathogenic bacteria by hedgehog-inspired magnetic nanoparticles microextraction.

Efficient separation of deoxyribonucleic acid (DNA) through magnetic nanoparticles (MN) is a widely used biotechnology. Hedgehog-inspired MNs (HMN) possess a high-surface-area due to the distinct burr-like structure of hedgehog, but there is no report about the usage of HMN for DNA extraction. Herein, to improve the selection of MN and illustrate the performance of HMN for DNA separation, HMN and silica-coated Fe3O4 nanoparticles (Fe3O4@SiO2) were fabricated and compared for the high-efficient separation of pathogenic bacteria of DNA. Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) are typical Gram-negative and Gram-positive bacteria and are selected as model pathogenic bacteria. To enhance the extraction efficiency of two kinds of MNs, various parameters, including pretreatment, lysis, binding and elution conditions, have been optimized in detail. In most separation experiments, the DNA yield of HMN was higher than that of Fe3O4@SiO2. Therefore, a HMN-based magnetic solid-phase microextraction (MSPE) and quantitative real-time PCR (qPCR) were integrated and used to detect pathogenic bacteria in real samples. Interestingly, the HMN-based MSPE combined qPCR strategy exhibited high sensitivity with a limit of detection of 2.0 × 101 CFU mL-1 for E. coli and 4.0 × 101 CFU mL-1 for S. aureus in orange juice, and 2.8 × 102 CFU mL-1 for E. coli and 1.1 × 102 CFU mL-1 for S. aureus in milk, respectively. The performance of the proposed strategy was significantly better than that of commercial kit. This work could prove that the novel HMN could be applicable for the efficient separation of DNA from complex biological samples.

Modeling and analysis of a tourism supply chain considering service level and advertising in the context of regular epidemic prevention and control under COVID-19.

In the context of regular epidemic prevention and control, this paper considers a two-stage tourism supply chain consisting of a scenic spot that attracts tourists through advertising and a travel agency that invests in service improvement and epidemic prevention. By establishing theoretical game models of a tourism supply chain, we investigate how the service level and advertising level can affect the retail price, product service level, and profits of the supply chain. The results show that the service level of travel agencies could improve consumers' preferences, expand the market demand for tourism products, and improve the efficiency of the supply chain to achieve a win-win situation and increase the profits of the scenic spot and the travel agency. The retailer price, service level, promotion level, and supply chain profit all increase as the service coefficient and advertising coefficient increase, and the speed of the increase is higher for the centralized model than for other models. Some valuable information could be provided for supply chain enterprises to develop collaborative strategies and promote tourism supply chain management practices.

Genetic Associations of Primary Angle-Closure Disease: A Systematic Review and Meta-Analysis.

Importance: Effects of genetic variants on primary angle-closure disease remained uncertain. Objective: To systematically review the associations of common single-nucleotide variants (SNVs) and rare coding variants with primary angle-closure disease, its subtypes (including primary angle-closure glaucoma, primary angle-closure suspect, and primary angle-closure) and progression. Data Sources: Eligible studies from PubMed, Embase, and Web of Science were retrieved up to April 3, 2023. SNV information was extracted from eligible reports and 2 genome-wide association studies summary statistics, UK BioBank and FinnGen. Study Selection: Studies providing analyzable genotype or allele data in a case-control design for primary angle-closure disease association and longitudinal case-only design for primary angle-closure disease progression. Data Extraction and Synthesis: PRISMA guidelines were used for literature screening and the Newcastle Ottawa Scale for data quality assessment. Pooled effect size with 95% CIs of SNV associations were calculated using fixed- or random-effect models according to I2 statistics. Main Outcomes and Measures: SNVs reported in 2 or more studies were meta-analyzed to generate pooled odds ratios and P values. Common and rare coding variants from single reports were summarized. Results: Sixty-nine citations were eligible for meta-analysis on overall primary angle-closure disease, involving 206 SNVs in 64 genes or loci. Seventeen SNVs in 15 genes or loci showed associations with primary angle-closure disease, and 15 SNVs in 13 genes or loci showed associations with primary angle-closure glaucoma. Two SNVs, ABCA1 rs2422493 and ZNRF3 rs3178915, were associated only with primary angle-closure disease. Two SNVs, PCMTD1-ST18 rs1015213 and COL11A1 rs3753841, were associated with primary angle-closure suspect, and 1 SNV, MMP9 rs3918249, was associated with primary angle-closure. This systematic review and meta-analysis newly confirmed 7 genes or loci associated with primary angle-closure glaucoma: ATOH7, CALCRL, FBN1, IL6, LOXL1, MMP19, and VAV3. Common and rare coding variants in 16 genes or loci that have been associated with primary angle-closure disease were cataloged. Stratification analysis revealed different primary angle-closure disease-associated genes in different ethnic populations. Only 1 study regarding the genetic association of primary angle-closure glaucoma progression was identified. Conclusions and Relevance: This study revealed the genetic complexity of primary angle-closure disease, involving common SNVs and rare coding variants in more than 30 genes or loci, with ethnic and phenotypic diversities. Further replication, genotype-phenotype correlation, and pathway analyses are warranted.

Assessment of progression of pulmonary fibrosis based on metabonomics and analysis of intestinal microbiota.

The main purpose of this study was to explore the changes of biomarkers in different developmental stages of bleomycin-induced pulmonary fibrosis (PF) in rats via comprehensive pathophysiology, UPLC-QTOF/MS metabonomic technology, and 16S rRNA gene sequencing of intestinal microbiota. The rats were randomly divided into normal control and 1-, 2- and 4-week model group. The rat model of PF was established by one-time intratracheal instillation of bleomycin. The levels of inflammatory and fibrosis-related factors such as hydroxyproline (HYP), type III procollagen (COL-III), type IV collagen (COL-IV), hyaluronidase (HA), laminin (LN), interleukin (IL)-1ß, IL-6, malondialdehyde (MDA) increased and superoxide dismutase (SOD) decreased as the PF cycle progressed. In the 1-, 2- and 4-week model group, 2, 19 and 18 potential metabolic biomarkers and 3, 16 and 12 potential microbial biomarkers were detected, respectively, which were significantly correlated. Glycerophospholipid metabolism pathway was observed to be an important pathway affecting PF at 1, 2 and 4 weeks; arginine and proline metabolism pathways significantly affected PF at 2 weeks. Linoleic acid metabolism pathway exhibited clear metabolic abnormalities at 2 and 4 weeks of PF, and alpha-linolenic acid metabolism pathway significantly affected PF at 4 weeks.

In this study, metabolomics technology and intestinal microbiota 16S rRNA gene sequencing were used to search for biomarkers with significant differences in each stage of pulmonary fibrosis. Finally, the variation characteristics of each stage of the disease were discussed. The hope is to provide new insights into the development of diagnostic biomarkers and potential therapeutic targets at all stages.

What kind of children do kindergarten teachers prefer? -Typology of the preferred types of children.

The teacher's pets are a common occurrence in the field of education. To investigate the preferences teachers exhibit toward certain children, the study focused on kindergarten teachers and employed a mixed research methodology. Initially, qualitative interviews were conducted with 15 kindergarten teachers to identify specific criteria influencing teacher preferences. Subsequently, A comprehensive model of teacher's pets was developed through a questionnaire survey involving 463 participants. This model encapsulated 32 distinct indicators, categorized into 7 types: children with good appearance (GA), exceptional abilities (OA), commendable conduct (GC), proactive and enthusiastic demeanor (PE), compliant and carefree nature (OC), children from vulnerable groups (VC), and those influenced by their parents (PI). The resulting model demonstrated a sound structure. Not only did it validate existing findings, but it also expanded upon the identified types of teacher's pets. An analysis based on game theory revealed the weighted combinations, highlighting the top three types of teacher's pets: children influenced by parental factors (24.3%), proactive and enthusiastic individuals (15.7%), and obedient, carefree children (14.8%), respectively. Conversely, the representation of vulnerable-concerned children (11.1%) was the lowest among the identified types.

Correction: Solution-processed white OLEDs with power efficiency over 90 lm W-1 by triplet exciton management with a high triplet energy level interfacial exciplex host and a high reverse intersystem crossing rate blue TADF emitter.

Correction for 'Solution-processed white OLEDs with power efficiency over 90 lm W-1 by triplet exciton management with a high triplet energy level interfacial exciplex host and a high reverse intersystem crossing rate blue TADF emitter' by Liang Chen et al., Mater. Horiz., 2022, 9, 1299-1308, https://doi.org/10.1039/D1MH02060A.

BRG1 mediates epigenetic regulation of TNFα-induced CCL2 expression in oral tongue squamous cell carcinoma cells.

Strong evidence has indicated that upregulation of chemokine (CC motif) ligand-2 (CCL2) expression and the presence of an inflammatory tumor microenvironment significantly contribute to the migratory and invasive properties of oral squamous cell carcinoma, specifically oral tongue squamous cell carcinoma (OTSCC). However, the precise epigenetic mechanism responsible for enhanced CCL2 expression in response to the inflammatory mediator tumor necrosis factor alpha (TNF-α) in OTSCC remains inadequately elucidated. We have demonstrated that the production of CCL2 can be induced by TNF-α, and this induction is mediated by the chromatin remodel protein BRG1. Through the use of a chromatin immunoprecipitation (ChIP) assay, we have found that BRG1 was involved in the recruitment of acetylated histones H3 and H4 at the CCL2 promoter, thereby activating TNF-α-induced CCL2 transcription. Furthermore, we have observed that recruitment of NF-κB p65 to the CCL2 promoter was increased following BRG1 overexpression and decreased after BRG1 knockdown in OTSCC cells. Our Re-ChIP assay has shown that BRG1 knockdown completely inhibits the recruitment of both acetylated histone H3 or H4 and NF-κB to the CCL2 promoter. In summary, the findings of our study demonstrate that BRG1 plays a significant role in mediating the production of CCL2 in OTSCC cells in response to TNF-α stimulation. This process involves the cooperative action of acetylated histone and NF-κB recruitment to the CCL2 promoter site. Our data suggest that BRG1 serves as a critical epigenetic mediator in the regulation of TNF-α-induced CCL2 transcription in OTSCC cells.

Effective prognostic risk model with cuproptosis-related genes in laryngeal cancer.

OBJECTIVE: Laryngeal cancer, characterized by high recurrence rates and a lack of effective biomarkers, has been associated with cuproptosis, a regulated cell death process linked to cancer progression. In this study, we aimed to explore the roles of cuproptosis-related genes in laryngeal cancer and their potential as prognostic markers and therapeutic targets. METHODS: We collected comprehensive data from The Cancer Genome Atlas and Gene Expression Omnibus databases, including gene expression profiles and clinical data of laryngeal cancer patients. Using clustering and gene analysis, we identified cuproptosis-related genes with prognostic significance. A risk model was constructed based on these genes, categorizing patients into high- and low-risk groups for outcome comparison. Univariate and multivariate analyses were conducted to identify independent prognostic factors, which were then incorporated into a nomogram. Gene Set Enrichment Analysis was employed to explore pathways distinguishing high- and low-risk groups. RESULTS: Our risk model, based on four genes, including transmembrane 2, dishevelled binding antagonist of ß-catenin 1, stathmin 2, and G protein-coupled receptor 173, revealed significant differences in patient outcomes between high- and low-risk groups. Independent prognostic factors were identified and integrated into a nomogram, providing a valuable tool for prognostic prediction. Gene Set Enrichment Analysis uncovered up-regulated pathways specifically associated with high-risk patient samples. CONCLUSION: This study highlights the potential of cuproptosis-related genes as valuable prognostic markers and promising therapeutic targets in the context of laryngeal cancer. This research sheds light on new avenues for understanding and managing this challenging disease. LEVEL OF EVIDENCE: Level 4.

How variable progenitor clones construct a largely invariant neocortex.

The neocortex contains a vast collection of diverse neurons organized into distinct layers. While nearly all neocortical neurons are generated by radial glial progenitors (RGPs), it remains largely unclear how a complex yet organized neocortex is constructed reliably and robustly. Here, we show that the division behavior and neuronal output of RGPs are highly constrained with patterned variabilities to support the reliable and robust construction of the mouse neocortex. The neurogenic process of RGPs can be well-approximated by a consistent Poisson-like process unfolding over time, producing deep to superficial layer neurons progressively. The exact neuronal outputs regarding layer occupation are variable; yet, this variability is constrained systematically to support all layer formation, largely reflecting the variable intermediate progenitor generation and RGP neurogenic entry and exit timing differences. Together, these results define the fundamental features of neocortical neurogenesis with a balanced reliability and variability for the construction of the complex neocortex.

High Contrast Bioimaging of Tumor and Inflammation with a Bicyclic Dioxetane Chemiluminescent Probe.

The link between inflammation and the evolution of cancer is well established. Visualizing and tracking both tumor proliferation and the associated inflammatory response within a living organism are vital for dissecting the nexus between these two processes and for crafting precise treatment modalities. We report the creation and synthesis of an advanced NIR chemiluminescence probe that stands out for its exceptional selectivity, extraordinary sensitivity at nanomolar concentrations, swift detection capabilities, and broad application prospects. Crucially, this probe has been successfully utilized to image endogenous ONOO- across different inflammation models, including abdominal inflammation triggered by LPS, subcutaneous inflammatory conditions, and tumors grafted onto mice. These findings highlight the significant promise of chemiluminescence imaging in enhancing our grasp of the intricate interplay between cancer and inflammation and in steering the development of potent, targeted therapeutic strategies.

[Spatiotemporal Evolution and Quantitative Attribution Analysis of Vegetation NDVI in Greater Khingan Mountains Forest-Steppe Ecotone].

It is of great significance to explore the dynamic variations in vegetation cover and to identify its driving factors for the restoration and sustainable development of the regional ecological environment. Based on MODIS NDVI data from 2000 to 2020 and contemporaneous meteorological, DEM, land use type, and other data, the spatiotemporal variation characteristics of vegetation in the Greater Khingan Mountains forest-steppe ecotone were deeply analyzed, and its future evolution pattern was predicted by using the methods of Sen+Mann-Kendall trend analysis and Hurst index. At the same time, the influence degree and mechanism of each detection factor and its interaction on vegetation spatial differentiation at the scale of the whole area and different physical geographic divisions were quantitatively revealed by introducing the GeoDetector model. The results showed that:① In terms of spatiotemporal variation, the spatiotemporal heterogeneity of NDVI in the Greater Khingan Mountains forest-steppe ecotone was obvious from 2000 to 2020. Temporally, NDVI fluctuated growth at a rate of 0.002 a-1 (P < 0.05) and underwent an upward mutation in 2011. Spatially, NDVI showed a distribution pattern of "increasing from southwest to northeast," and the NDVI grade transfer was mainly "medium vegetation cover→medium-high vegetation cover" during the 21 years, and the area of vegetation improvement was much larger than that of degradation. ② In terms of trend prediction, the future variation trend of NDVI in the Greater Khingan Mountains forest-steppe ecotone was mainly continuous improvement, accounting for 37%, but was mostly weakly sustained. ③ In terms of driving mechanism, the wind speed, evaporation, and relative humidity had the most significant influence on the spatial differentiation of NDVI over the whole area. The influence of natural factors has been decreasing over the past 21 years, whereas the influence of human factors has been increasing, and the main driving factors of NDVI spatial differentiation were quite different in different vegetation, climate, soil, and geomorphic zones. The synergistic effect between each factor at different spatial scales all showed two-factor or non-linear enhancement relationships, which was significantly enhanced compared with the single-factor effect. This study contributes to clarifying the causes of ecological fragility in the forest-steppe ecotone in the northern cold region and provides scientific support for formulating differentiated protection and management plans for vegetation resources under different environmental conditions.

Metal-Free Activation of Molecular Oxygen by 9-Fluorenone-Based Porous Organic Polymers for Selective Aerobic Oxidation.

Oxygen activation is a critical step in heterogeneous oxidative processes, particularly in catalytic, electrolytic, and pharmaceutical applications. Among the various catalysts available for photocatalytic O2 activation, homogeneous aryl ketones are at the forefront. To avoid the degradation and deactivation of aryl ketones, 9-fluorenone-based porous organic polymers were designed and regulated by doping them with co-monomers. The obtained heterogeneous photocatalyst showed good performance in O2 activation, and its performance was better than that of homogeneous 9-fluorenone. The obtained heterogeneous photocatalyst showed good reusability. We believe that the presented method and findings represent an important step toward designing catalysts tailored for specific tasks.

Hydrogenation of levulinic acid to γ-valerolactone over hydrophobic Ru@HCP catalysts.

This study introduces an efficient strategy for promoting the synthesis of γ-valerolactone (GVL) via levulinic acid (LA) hydrogenation. A series of hyper-crosslinked porous polymer (HCP) supported Ru catalysts with different monomers were prepared. The wettabilities were controlled by the surface functional groups. The hydrophobic catalysts showed much higher activity than the hydrophilic ones in the hydrogenation of LA to GVL, highly possible due to the substrate enrichment. Further insight showed that the reaction proceeded through the 4-HVA route. These results illustrated the importance of surface wettability in bio-based molecule upgrading, which is beneficial for catalyst design.

Clinical features, surgical treatment, and long-term outcomes of moyamoya disease in a single institution of Fujian, Southeast China: A retrospective study.

At present, detailed demographic and clinical data of moyamoya disease (MMD) in the population of Southeast China are lacking. Therefore, this study aimed to evaluate the epidemiological and clinical features of MMD in Southeast China. Our cohort included 170 patients diagnosed with MMD over the preceding 5 years. Clinical characteristics were obtained through a retrospective chart review, while follow-up information and outcomes were obtained through clinical visits and imaging. The median age at symptom onset was 49 years (range 4-73), with a peak in the age distribution observed at 41 to 60 years. The female-to-male ratio was 1.125 (90/80), and the ratio of the ischemic type to the hemorrhagic type was 2.33 (119/50). The most common initial symptom was an ischemic event. The 5-year Kaplan-Meier risk of stroke was 4.9% for all patients treated with surgical revascularization. Of all patients, 83.9% were able to live independently with no significant disability, and 89.8% showed improved cerebral hemodynamics. Our study provided detailed demographic and clinical data on Southeastern Chinese patients with MMD, which was consistent with findings in other parts of China. Raising clinical awareness of MMD in primary hospitals is important to facilitate early diagnosis and timely treatment of MMD patients.

Cordycepin improves sensitivity to temozolomide in glioblastoma cells by down-regulating MYC.

PURPOSE: Glioblastoma is one of the malignant tumors with poor prognosis and no effective treatment is available at present. METHODS: To study the effect of cordycepin combined with temozolomide on glioblastoma, we explored the effect of the combination based on network pharmacology and biological verification. RESULTS: It was found that the drug combination significantly inhibited the cell growth, proliferation, migration and invasion of LN-229 cells. Drug combination inhibited epithelial-mesenchymal transition (EMT) by up-regulating the expression of E-cadherin and suppressing the expression of N-cadherin, Zeb1 and Twist1. Through network pharmacology, we further explored the molecular mechanism of drug combination against glioblastoma, and 36 drug-disease common targets were screened. The GO biological process analysis included 44 items (P < 0.01), which mainly involved the regulation of apoptosis, cell proliferation, cell migration, etc. The enrichment analysis of KEGG pathways included 28 pathways (P < 0.05), and the first four pathways were "MicroRNA in cancer, Proteoglycans in cancer, Pathways in cancer and PI3K-AKT signaling pathway". We detected the expression of important genes in the pathways and PPI network, and the results showed that the drug combination down-regulated NFKB1, MYC, MMP-9, MCL1, CTNNB1, and up-regulated PDCD4. CONCLUSION: Cordycepin combined with temozolomide may down-regulate MYC through "MicroRNA in cancer, Proteoglycans in cancer, Pathways in cancer and PI3K-AKT signaling pathway", which in turn regulate the expression of MCL1, CTNNB1, MMP9, PDCD4, thus regulating cell proliferation, migration and apoptosis in glioblastoma.

Synthesis of micron-sized magnetic agarose beads chelated with nickel ions towards the affinity-based separation of histidine-tagged/rich proteins.

Developing high-performance magnetic particles for the effective separation and purification of target proteins has become an important topic in the area of biomedical research. In this work, a simple and novel strategy was proposed for fabricating magnetic Fe3O4@agarose-iminodiacetic acid-Ni microspheres (MAIN), which can efficiently and selectively isolate histidine-tagged/rich proteins (His-proteins). Based on the thermoreversible sol-gel transition of agarose, basic magnetic agarose microspheres were prepared through the inverse emulsion method, in which the emulsion contained agarose and amine-modified Fe3O4 nanoparticles. The size of the emulsion was controlled by the emulsification of a high-speed shear machine, which improved the specific surface area of MAIN. Subsequently, the amine-modified Fe3O4 nanoparticles were covalently crosslinked with agarose through epichlorohydrin, which could avoid leakage of the magnetic source during use and increase the stability of MAIN. The microsized MAIN exhibited a clearly visible spherical core-shell structure with a diameter range from 3.4 µm to 9.8 µm, and excellent suspension ability in aqueous solution. The maximum adsorption capacity of MAIN for histidine-rich bovine hemoglobin was 1069.2 mg g-1 at 35 °C, which was higher than those of commercialized and most reported magnetic agarose microspheres/nanoparticles. The MAIN showed excellent adsorption ability and selectivity toward His-proteins in a mixture of histidine-rich bovine serum albumin (BSA) and histidine-poor lysozyme (LYZ). When the amount of LYZ was 5-fold higher than that of BSA, the recovery of BSA reached 75.0%. To prove its practicability, MAIN was successfully employed for the enrichment of histidine-tagged RSV-F0 from the cell culture medium supernatant. According to the optimized conditions, MAIN could enrich approximately 0.1 mg of RSV-F0 from 1 mL of complex biological sample. Therefore, we believe that the novel MAIN could be applicable for efficient separation and purification of His-proteins from complex biological systems.

Direct blue 53, a biological dye, inhibits SARS-CoV-2 infection by blocking ACE2 and spike interaction in vitro and in vivo.

COVID-19 is a global health problem caused by SARS-CoV-2, which has led to over 600 million infections and 6 million deaths. Developing novel antiviral drugs is of pivotal importance to slow down the epidemic swiftly. In this study, we identified five azo compounds as effective antiviral drugs to SARS-CoV-2, and mechanism study revealed their targets for impeding viral particles' ability to bind to host receptors. Direct Blue 53, which displayed the strongest inhibitory impact, inhibited five mutant strains at micromole. In vitro, mechanism study demonstrated Direct Blue 53 inhibited viral infection through interaction with the spike of SARS-CoV-2. And 25 mg/kg/d compound treatment showed 50% or 60% survival protection against lethal Delta or Omicron BA.2 infection in vivo. Taken together, our results demonstrate that azo compounds with dimethyl-biphenyl-diyl-bis(azo)bis structure may be promising anti-SARS-CoV-2 drug candidates, which provide practicable therapies with the aid of structural optimizations and further research.