Homeostatic functions of monocytes and interstitial lung macrophages are regulated via collagen domain-binding receptor LAIR1.

Myeloid cells encounter stromal cells and their matrix determinants on a continual basis during their residence in any given organ. Here, we examined the impact of the collagen receptor LAIR1 on myeloid cell homeostasis and function. LAIR1 was highly expressed in the myeloid lineage and enriched in non-classical monocytes. Proteomic definition of the LAIR1 interactome identified stromal factor Colec12 as a high-affinity LAIR1 ligand. Proteomic profiling of LAIR1 signaling triggered by Collagen1 and Colec12 highlighted pathways associated with survival, proliferation, and differentiation. Lair1-/- mice had reduced frequencies of Ly6C- monocytes, which were associated with altered proliferation and apoptosis of non-classical monocytes from bone marrow and altered heterogeneity of interstitial macrophages in lung. Myeloid-specific LAIR1 deficiency promoted metastatic growth in a melanoma model and LAIR1 expression associated with improved clinical outcomes in human metastatic melanoma. Thus, monocytes and macrophages rely on LAIR1 sensing of stromal determinants for fitness and function, with relevance in homeostasis and disease.

The innate immune sensor NLRC3 attenuates Toll-like receptor signaling via modification of the signaling adaptor TRAF6 and transcription factor NF-κB.

Several members of the NLR family of sensors activate innate immunity. In contrast, we found here that NLRC3 inhibited Toll-like receptor (TLR)-dependent activation of the transcription factor NF-κB by interacting with the TLR signaling adaptor TRAF6 to attenuate Lys63 (K63)-linked ubiquitination of TRAF6 and activation of NF-κB. We used bioinformatics to predict interactions between NLR and TRAF proteins, including interactions of TRAF with NLRC3. In vivo, macrophage expression of Nlrc3 mRNA was diminished by the administration of lipopolysaccharide (LPS) but was restored when cellular activation subsided. To assess biologic relevance, we generated Nlrc3(-/-) mice. LPS-treated Nlrc3(-/-) macrophages had more K63-ubiquitinated TRAF6, nuclear NF-κB and proinflammatory cytokines. Finally, LPS-treated Nlrc3(-/-) mice had more signs of inflammation. Thus, signaling via NLRC3 and TLR constitutes a negative feedback loop. Furthermore, prevalent NLR-TRAF interactions suggest the formation of a 'TRAFasome' complex.

Insight into Eu3+-Doped Phase-Change K3Lu(PO4)2 Phosphate toward Data Encryption.

Adjusting the local coordination environment of lanthanide luminescent ions can modulate their crystal-field splittings and broaden their applications in the relevant optical fields. Here, we introduced Eu3+ ions into the phase-change K3Lu(PO4)2 phosphate and found that the temperature-induced reversible phase transitions of K3Lu(PO4)2 (phase I ⇆ phase II and phase II ⇆ phase III, below room temperature) give rise to an obvious photoluminescence (PL) difference of Eu3+ ions. The Eu3+ emission mainly focused on the 5D0 → 7F1 transition in phase III but manifested comparable 5D0 → 7F1,2 transitions in the two low-temperature phases. On this basis, the change of Eu3+-doped concentration led to the phase evolution in Eu3+:K3Lu(PO4)2, which could stabilize two types of low-temperature polymorphs to the specific temperature by controlling the doping content. Finally, we proposed a feasible information encryption strategy based on the PL modulation of Eu3+:K3Lu(PO4)2 phosphors, which was caused by the temperature hysteresis of the relevant phase transition, exhibiting good stability and reproducibility. Our findings pave an avenue for exploring the optical application of lanthanide-based luminescent materials by introducing phase-change hosts.

"Human and Mouse Cross-Reactive" Albumin-Binding Helix-Loop-Helix Peptide Tag for Prolonged Bioactivity of Therapeutic Proteins.

The effectiveness of protein and peptide pharmaceuticals depends essentially on their intrinsic pharmacokinetics. Small-sized pharmaceuticals in particular often suffer from short serum half-lives due to rapid renal clearance. To improve the pharmacokinetics by association with serum albumin (SA) in vivo, we generated an SA-binding tag of a helix-loop-helix (HLH) peptide to be linked with protein pharmaceuticals. For use in future preclinical studies, screening of yeast-displayed HLH peptide libraries against human SA (HSA) and mouse SA (MSA) was alternately repeated to give the SA-binding peptide AY-VE, which exhibited cross-binding activities to HSA and MSA with KD of 65 and 20 nM, respectively. As a proof of concept, we site-specifically conjugated peptide AY-VE with insulin to examine its bioactivity in vivo. In mouse bioassay monitoring the blood glucose level, the AY-VE conjugate was found to have a prolonged hypoglycemic effect for 12 h. The HLH peptide tag is a general platform for extending the bioactivity of therapeutic peptides or proteins.

Using a peptide-based mass spectrometry approach to quantitate proteolysis of an intact heterogeneous procollagen substrate by BMP1 for antagonistic antibody screening.

Proteases are critical proteins involved in cleaving substrates that may impact biological pathways, cellular processes, or disease progression. In the biopharmaceutical industry, modulating the levels of protease activity is an important strategy for mitigating many types of diseases. While a variety of analytical tools exist for characterizing substrate cleavages, in vitro functional screening for antibody inhibitors of protease activity using physiologically relevant intact protein substrates remains challenging. In addition, detecting such large protein substrates with high heterogeneity using high-throughput mass spectrometry screening has rarely been reported in the literature with concerns for assay robustness and sensitivity. In this study, we established a peptide-based in vitro functional screening assay for antibody inhibitors of mouse bone morphogenic protein 1 (mBMP1) metalloprotease using a heterogeneous recombinant 66-kDa mouse Procollagen I alpha 1 chain (mProcollagen) substrate. We compared several analytical tools including capillary gel electrophoresis Western blot (CE-Western blot), as well as both intact protein and peptide-based mass spectrometry (MS) to quantitate the mBMP1 proteolytic activity and its inhibition by antibodies using this heterogeneous mProcollagen substrate. We concluded that the peptide-based mass spectrometry screening assay was the most suitable approach in terms of throughput, sensitivity, and assay robustness. We then optimized our mBMP1 proteolysis reaction after characterizing the enzyme kinetics using the peptide-based MS assay. This assay resulted in Z' values ranging from 0.6 to 0.8 from the screening campaign. Among over 1200 antibodies screened, IC50 characterization was performed on the top candidate hits, which showed partial or complete inhibitory activities against mBMP1.

Identification and Characterization of a Novel Endo-ß-1,4-Xylanase from Streptomyces sp. T7 and Its Application in Xylo-Oligosaccharide Production.

A xylanase-producing strain, identified as Streptomyces sp. T7, was isolated from soil by our lab. The endo-ß-1,4-xylanase (xynST7) gene was found in the genome sequence of strain T7, which was cloned and expressed in Escherichia coli. XynST7 belonged to the glycoside hydrolase family 10, with a molecular mass of approximately 47 kDa. The optimum pH and temperature of XynST7 were pH 6.0 and 60 °C, respectively, and it showed wide pH and temperature adaptability and stability, retaining more than half of its enzyme activity between pH 5.0 and 11.0 below 80 °C. XynST7 showed only endo-ß-1,4-xylanase activity without cellulase- or ß-xylosidase activity, and it showed maximal hydrolysis for corncob xylan in all the test substrates. Then, XynST7 was used for the production of xylo-oligosaccharides (XOSs) by hydrolyzing xylan extracted from raw corncobs. The maximum yield of the XOS was 8.61 ± 0.13 mg/mL using 15 U/mL of XynST7 and 1.5% corncob xylan after 10 h of incubation at 60 °C. The resulting hydrolysate products mainly consisted of xylobiose and xylotriose. These data indicated that XynST7 might by a promising tool for various industrial applications.

Extracellular BMP1 is the major proteinase for COOH-terminal proteolysis of type I procollagen in lung fibroblasts.

Proteolytic processing of procollagens is a central step during collagen fibril formation. Bone morphogenic protein 1 (BMP1) is a metalloprotease that plays an important role in the cleavage of carboxy-terminal (COOH-terminal) propeptides from procollagens. Although the removal of propeptides is required to generate mature collagen fibrils, the contribution of BMP1 to this proteolytic process and its action site remain to be fully determined. In this study, using postnatal lung fibroblasts as a model system, we showed that genetic ablation of Bmp1 in primary murine lung fibroblasts abrogated COOH-terminal cleavage from type I procollagen as measured by COOH-terminal propeptide of type I procollagen (CICP) production. We also showed that inhibition of BMP1 by siRNA-mediated knockdown or small-molecule inhibitor reduced the vast majority of CICP production and collagen deposition in primary human lung fibroblasts. Furthermore, we discovered and characterized two antibody inhibitors for BMP1. In both postnatal lung fibroblast and organoid cultures, BMP1 blockade prevented CICP production. Together, these findings reveal a nonredundant role of extracellular BMP1 to process CICP in lung fibroblasts and suggest that development of antibody inhibitors is a viable pharmacological approach to target BMP1 proteinase activity in fibrotic diseases.

Robust Anode-Supported Cells with Fast Oxygen Release Channels for Efficient and Stable CO2 Electrolysis at Ultrahigh Current Densities.

High-temperature electrolysis using solid oxide electrolysis cells (SOECs) provides a promising way for the storage of renewable energy into chemical fuels. During the past, nickel-based cathode-supported thin-film electrolyte configuration was widely adopted. However, such cells suffer from the serious challenge of anode delamination at high electrolysis currents due to enormous gaseous oxygen formation at the anode-electrolyte interface with insufficient adhesion caused by low sintering temperatures for ensuring high anode porosity and cathode pulverization because of potential nickel redox reaction. Here, the authors propose, fabricate, and test asymmetric thick anode-supported SOECs with firm anode-electrolyte interface and graded anode gas diffusion channel for realizing efficient and stable electrolysis at ultrahigh currents. Such a specially structured anode allows the co-sintering of anode support and electrolyte at high temperatures to form strong interface adhesion while suppressing anode sintering. The mixed oxygen-ion and electron conducting anode with graded channel structure provides a fast oxygen release pathway, large anode surface for oxygen evolution reaction, and excellent support for depositing nanocatalysts, to further improve oxygen evolution activity. As a result, the as-prepared cells demonstrate both high performance, comparable or even higher than state-of-the-art cathode-supported SOECs, and outstanding stability at a record current density of 2.5 A cm-2 .

Enhancing the Photoluminescence Property of Pr3+ Ions by Understanding the Polymorphous Influence of the K3Lu(PO4)2 Host.

Adjusting the local coordination environment of lanthanide luminescent ions is a useful method to manipulate the relevant photoluminescence (PL) property. K3Lu(PO4)2 is a phase-change material, and according to the stable temperature range from low to high, the related polymorphs are phase I [P21/m, coordination number (CN) of Lu3+ = 7], phase II (P21/m, CN = 6), and phase III (P3̅, CN = 6), respectively. Based on the temperature-dependent PL analysis of K3Lu(PO4)2:Pr3+, we find that Pr3+ ions occupy the noninversion sites (Cs) in the two low-temperature phases but preferentially enter into the inversion ones (C3i) in phase III. Compared to Pr3+-doped phase I (78 K), Pr3+ ions in phase III (300 K) manifest a weaker fluorescence intensity (170-fold lower). To enhance the room-temperature PL property of K3Lu(PO4)2:Pr3+, a polymorphous adjustment strategy was proposed by the use of the ion-doping method. By introducing the Gd3+ ions into the lattice, Pr3+-doped phase I is successfully stabilized to room temperature, manifesting a 27-fold fluorescence increase in comparison to K3Lu(PO4)2:Pr3+ (0.1 at. %). The finding discussed in this study highlights the significance of site engineering for luminescent ions and also presents the application value of phase-change hosts in the development of high-performance luminescent materials.

Enhancement of angucycline production by combined UV mutagenesis and ribosome engineering and fermentation optimization in Streptomyces dengpaensis XZHG99T.

Strain improvement of Streptomyces dengpaensis XZHG99T was performed by combined UV mutagenesis and ribosome engineering, as well as fermentation optimization for enhanced angucycline production (rabelomycin and saquayamycin B1). First, four streptomycin-resistant mutants were obtained after screening of UV mutagenesis and ribosome engineering. Then a rpsL mutant (HTT7) with higher productivity of rabelomycin and saquayamycin B1 was selected according to genetic screening and HPLC/LC-MS analyses, whose maximum titers of rabelomycin and saquayamycin B1 were 3.6 ± 0.02 mg/L and 7.5 ± 0.04 mg/L, respectively, about fourfold higher than those produced by XZHG99T. Next, fermentation optimization of HTT7 was successively carried out by single-factor experiments in shake flasks. The titers of rabelomycin and saquayamycin B1 were increased to 11.2 ± 0.04 mg/L and 20.5 ± 0.02 mg/L after optimization of shake flask fermentation conditions, respectively, which was increased about sixfold compared with those produced by XZHG99T. Finally, the titers of rabelomycin and saquayamycin B1 reached 15.7 ± 0.05 mg/L and 39.9 ± 0.05 mg/L after the scaled-up fermentation, which was 7.8-fold and 11.4-fold higher than those produced by XZHG99T, respectively. These data demonstrate that the combined empirical strain-breeding approaches are still an effective and convenient pathway to improve strain production ability.

Streptomyces tibetensis sp. nov., an actinomycete isolated from the Tibetan Plateau.

A novel actinomycete, designated strain XZ 46T, was isolated from acid sandy soil collected from the Tibetan Plateau, China. Its taxonomic position was determined using a polyphasic approach. Strain XZ 46T shows the typical morphological and chemotaxonomic features of members of the genus Streptomyces: slightly yellow to brown substrate mycelia and grayish white to slightly yellow aerial hyphae forming cylindrical and spiny spores; meso-diaminopimelic acid in the cell wall peptidoglycan; MK-9(H8), MK-9(H4) and MK-9(H2) as predominant menaquinones; diphosphatidylglycerol, phospatidylethanolamine, phosphatidylglycerol and phosphatidylinositol as main polar lipids; and iso-C15:0, iso-C16:0 and anteiso-C15:0 as major cellular fatty acids. The G+C content of the draft genome sequence, consisting of 8,995,813 bp, is 71.23%. The16S rRNA gene sequence analysis indicated that strain XZ 46T shows high sequence similarity to Streptomyces luteogriseus NBRC 13402T as well as forming an independent lineage clade with it in phylogenetic trees. Multilocus sequence analysis (MLSA) of five housekeeping genes (atpD, gyrB, recA, rpoB and trpB) illustrated that Streptomyces hawaiiensis is also a very closely related taxon. However, DNA-DNA hybridization, MLSA evolutionary distance and phenotypic properties demonstrate that strain XZ 46T can be distinguished from these phylogenetically related Streptomyces species. Therefore, it is concluded that strain XZ 46T represents a novel species of the genus Streptomyces, for which the name Streptomyces tibetensis is sp. nov. proposed. The type strain is XZ 46T (= CGMCC 4.7579T = KCTC 49221T).

Preparation of a γ-Fe2 O3 /Ag nanowire coaxial nanocable for high-performance lithium-ion batteries.

In this study, we report the design and synthesis of a silver nanowire-γ-Fe2 O3 coaxial nanocable architecture (Ag NWs@γ-Fe2 O3 nanocable) through mild oxidation of [Fe(CO)5 ] on the surface of silver nanowires followed by a calcination process. After optimization of the structural design, the Ag NWs@γ-Fe2 O3 nanocable could deliver superior lithium storage performance in terms of high reversible capacity, good rate performance, and excellent stability, such as a high reversible capacity of about 890 mA h g(-1) after 60 cycles at a current rate of 0.1 C (1.0 C=1005 mA g(-1) ). The reversible capacity remains as high as about 550 mA h g(-1) even at a high current rate of 2.0 C. This dramatic performance is mainly attributed to the smart coaxial design, which can not only alleviate the large volume change and prevent the aggregation of γ-Fe2 O3 nanoparticles, but also enables good conductivity and thus enhances fast charge transfer. The unique structural features of the Ag NWs@γ-Fe2 O3 nanocable represent a promising anode material in lithium-ion battery applications.

[Isolation and Study on the Aflatoxin Genes of Aflatoxin-producing Fungi in Paprika Samples in Chengdu].

OBJECTIVE: To isolate aflatoxin-producing strains from paprika samples and to do a preliminarily study on the relationship between aflatoxin-producing ability and the genes aflR, omt-1 and ver-1. METHODS: Fungi were isolated by traditional culture method. Potential aflatoxin-producing strains were screened by phenotypic traits and multiplex PCR. After these potential aflatoxin-producing strains cultured in the toxigenic culture medium, the levels of aflatoxin B, (AFB1) of the cultures were tested with ELISA method. The phylogenetic tree of aflR, omt-1 and ver-1 was constructed to explore the relationship between these genes and the AFB1-producing capacity. RESULTS: 17 potential aflatoxin-producing fungi were isolated. The ratio of positive toxigenic strains is 64. 71%. 11 isolates were positive in AFB1 detection while existing high sequence homology with AS 3. 4408, 6 isolates were negative in AFB1 detection while existing high sequence homology with Aspergillus oryzae. CONCLUSION: Aspergillus flavus are potential candidates for aflatoxin control. Not all Aspergillus flavus have AFB1-producing capacity, aflR gene had a direct relation to AFB1-producing capacity, while ver-1 and omt-1 were related to the level of AFB1 producing.

NLRX1 is a regulator of mitochondrial antiviral immunity.

The RIG-like helicase (RLH) family of intracellular receptors detect viral nucleic acid and signal through the mitochondrial antiviral signalling adaptor MAVS (also known as Cardif, VISA and IPS-1) during a viral infection. MAVS activation leads to the rapid production of antiviral cytokines, including type 1 interferons. Although MAVS is vital to antiviral immunity, its regulation from within the mitochondria remains unknown. Here we describe human NLRX1, a highly conserved nucleotide-binding domain (NBD)- and leucine-rich-repeat (LRR)-containing family member (known as NLR) that localizes to the mitochondrial outer membrane and interacts with MAVS. Expression of NLRX1 results in the potent inhibition of RLH- and MAVS-mediated interferon-beta promoter activity and in the disruption of virus-induced RLH-MAVS interactions. Depletion of NLRX1 with small interference RNA promotes virus-induced type I interferon production and decreases viral replication. This work identifies NLRX1 as a check against mitochondrial antiviral responses and represents an intersection of three ancient cellular processes: NLR signalling, intracellular virus detection and the use of mitochondria as a platform for anti-pathogen signalling. This represents a conceptual advance, in that NLRX1 is a modulator of pathogen-associated molecular pattern receptors rather than a receptor, and identifies a key therapeutic target for enhancing antiviral responses.

Antiviral activity of curcumin and its analogs selected by an artificial intelligence-supported activity prediction system in SARS-CoV-2-infected VeroE6 cells.

Curcumin has been reported to exert its anti-SARS-CoV-2 activity by inhibiting the binding of spike receptor-binding domain (RBD) to angiotensin-converting enzyme-2 (ACE2). To identify more potent compounds, we evaluated the antiviral activities of curcumin and its analogs in SARS-CoV-2-infected cells. An artificial intelligence-supported activity prediction system was used to select the compounds, and 116 of the 334 curcumin analogs were proposed to have spike RBD-ACE2 binding inhibitory activity. These compounds were narrowed down to eight compounds for confirmatory studies. Six out of the eight compounds showed antiviral activity with EC50 values of less than 30 µM and binding inhibitory activity with IC20 values of less than 30 µM. Structure-activity relationship analyses revealed that the double bonds in the carbon chain connecting the two phenolic groups were essential for both activities. X-ray co-crystallography studies are needed to clarify the true binding pose and design more potent derivatives.

Flexible Composite Electrolyte Membranes with Fast Ion Transport Channels for Solid-State Lithium Batteries.

Numerous endeavors have been dedicated to the development of composite polymer electrolyte (CPE) membranes for all-solid-state batteries (SSBs). However, insufficient ionic conductivity and mechanical properties still pose great challenges in practical applications. In this study, a flexible composite electrolyte membrane (FCPE) with fast ion transport channels was prepared using a phase conversion process combined with in situ polymerization. The polyvinylidene fluoride-hexafluoro propylene (PVDF-HFP) polymer matrix incorporated with lithium lanthanum zirconate (LLZTO) formed a 3D net-like structure, and the in situ polymerized polyvinyl ethylene carbonate (PVEC) enhanced the interface connection. This 3D network, with multiple rapid pathways for Li+ that effectively control Li+ flux, led to uniform lithium deposition. Moreover, the symmetrical lithium cells that used FCPE exhibited high stability after 1200 h of cycling at 0.1 mA cm-2. Specifically, all-solid-state lithium batteries coupled with LiFePO4 cathodes can stably cycle for over 100 cycles at room temperature with high Coulombic efficiencies. Furthermore, after 100 cycles, the infrared spectrum shows that the structure of FCPE remains stable. This work demonstrates a novel insight for designing a flexible composite electrolyte for highly safe SSBs.

Structure- and machine learning-guided engineering demonstrate that a non-canonical disulfide in an anti-PD-1 rabbit antibody does not impede antibody developability.

Rabbits produce robust antibody responses and have unique features in their antibody repertoire that make them an attractive alternative to rodents for in vivo discovery. However, the frequent occurrence of a non-canonical disulfide bond between complementarity-determining region (CDR) H1 (C35a) and CDRH2 (C50) is often seen as a liability for therapeutic antibody development, despite limited reports of its effect on antibody binding, function, and stability. Here, we describe the discovery and humanization of a human-mouse cross-reactive anti-programmed cell death 1 (PD-1) monoclonal rabbit antibody, termed h1340.CC, which possesses this non-canonical disulfide bond. Initial removal of the non-canonical disulfide resulted in a loss of PD-1 affinity and cross-reactivity, which led us to explore protein engineering approaches to recover these. First, guided by the sequence of a related clone and the crystal structure of h1340.CC in complex with PD-1, we generated variant h1340.SA.LV with a potency and cross-reactivity similar to h1340.CC, but only partially recovered affinity. Side-by-side developability assessment of both h1340.CC and h1340.SA.LV indicate that they possess similar, favorable properties. Next, and prompted by recent developments in machine learning (ML)-guided protein engineering, we used an unbiased ML- and structure-guided approach to rapidly and efficiently generate a different variant with recovered affinity. Our case study thus indicates that, while the non-canonical inter-CDR disulfide bond found in rabbit antibodies does not necessarily constitute an obstacle to therapeutic antibody development, combining structure- and ML-guided approaches can provide a fast and efficient way to improve antibody properties and remove potential liabilities.

Nonclinical immunogenicity risk assessment for knobs-into-holes bispecific IgG1 antibodies.

Bispecific antibodies, including bispecific IgG, are emerging as an important new class of antibody therapeutics. As a result, we, as well as others, have developed engineering strategies designed to facilitate the efficient production of bispecific IgG for clinical development. For example, we have extensively used knobs-into-holes (KIH) mutations to facilitate the heterodimerization of antibody heavy chains and more recently Fab mutations to promote cognate heavy/light chain pairing for efficient in vivo assembly of bispecific IgG in single host cells. A panel of related monospecific and bispecific IgG1 antibodies was constructed and assessed for immunogenicity risk by comparison with benchmark antibodies with known low (Avastin and Herceptin) or high (bococizumab and ATR-107) clinical incidence of anti-drug antibodies. Assay methods used include dendritic cell internalization, T cell proliferation, and T cell epitope identification by in silico prediction and MHC-associated peptide proteomics. Data from each method were considered independently and then together for an overall integrated immunogenicity risk assessment. In toto, these data suggest that the KIH mutations and in vitro assembly of half antibodies do not represent a major risk for immunogenicity of bispecific IgG1, nor do the Fab mutations used for efficient in vivo assembly of bispecifics in single host cells. Comparable or slightly higher immunogenicity risk assessment data were obtained for research-grade preparations of trastuzumab and bevacizumab versus Herceptin and Avastin, respectively. These data provide experimental support for the common practice of using research-grade preparations of IgG1 as surrogates for immunogenicity risk assessment of their corresponding pharmaceutical counterparts.

Identification of SARS-CoV-2 main protease inhibitors from FDA-approved drugs by artificial intelligence-supported activity prediction system.

Although a certain level of efficacy and safety of several vaccine products against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been established, unmet medical needs for orally active small molecule therapeutic drugs are still very high. As a key drug target molecule, SARS-CoV-2 main protease (Mpro) is focused and large number of in-silico screenings, a part of which were supported by artificial intelligence (AI), have been conducted to identify Mpro inhibitors both through drug repurposing and drug discovery approaches. In the many drug-repurposing studies, docking simulation-based technologies have been mainly employed and contributed to the identification of several Mpro binders. On the other hand, because AI-guided INTerprotein's Engine for New Drug Design (AI-guided INTENDD), an AI-supported activity prediction system for small molecules, enables to propose the potential binders by proprietary AI scores but not docking scores, it was expected to identify novel potential Mpro binders from FDA-approved drugs. As a result, we selected 20 potential Mpro binders using AI-guided INTENDD, of which 13 drugs showed Mpro-binding signal by surface plasmon resonance (SPR) method. Six (6) compounds among the 13 positive drugs were identified for the first time by the present study. Furthermore, it was verified that vorapaxar bound to Mpro with a Kd value of 27 µM by SPR method and inhibited virus replication in SARS-CoV-2 infected cells with an EC50 value of 11 µM. Communicated by Ramaswamy H. Sarma.

Modulating red mud for the fabrication of cementitious material by analyzing the thermal evolution of hydrogarnets.

This work aims to develop a modulation strategy for converting red mud (RM) into cementitious material based on elucidating the phase transformation of hydrogarnet. The results show that cementitious minerals 2CaO·SiO2 (C2S), 12CaO·7Al2O3 (C12A7), and 4CaO·Al2O3·Fe2O3 (C4AF), as well as the free iron minerals Fe and FeO, are formed by integrating calcification dealkalization and reduction roasting treatment of RM. During the reduction roasting process, CaO is preferentially combined with SiO2 and Al2O3 to form cementitious minerals, and the Fe(III) compounds in hydrogarnet and hematite can be directly reduced to free iron minerals without intermediate ferrites. By optimizing the reduction roasting parameters and eliminating the useless minerals 2CaO·Al2O3·SiO2 (C2AS), and FeO, the reduction roasting product is mainly composed of C2S, C12A7, C4AF, and Fe. Therefore, cementitious material is obtained after the magnetic separation of Fe, which possesses both early and late hydration properties. In addition, 75% Fe in RM can be recovered, and the reduced iron powder (RIP) is also useful in the cement clinker production or steel smelting process. The findings in this work lay the foundations for understanding the phase transformation of RM-derived hydrogarnet in the reduction roasting process and also provide a new reference for the modulation and utilization of RM in the cement and concrete field.