Interaction Sites Research Articles

Endogenous oligomer formation underlies DVL2 condensates and promotes Wnt/β-catenin signaling

Activation of the Wnt/β-catenin pathway crucially depends on the polymerization of dishevelled 2 (DVL2) into biomolecular condensates. However, given the low affinity of known DVL2 self-interaction sites and its low cellular concentration, it is unclear how polymers can form. Here, we detect oligomeric DVL2 complexes at endogenous protein levels in human cell lines, using a biochemical ultracentrifugation assay. We identify a low-complexity region (LCR4) in the C-terminus whose deletion and fusion decreased and increased the complexes, respectively. Notably, LCR4-induced complexes correlated with the formation of microscopically visible multimeric condensates. Adjacent to LCR4, we mapped a conserved domain (CD2) promoting condensates only. Molecularly, LCR4 and CD2 mediated DVL2 self-interaction via aggregating residues and phenylalanine stickers, respectively. Point mutations inactivating these interaction sites impaired Wnt pathway activation by DVL2. Our study discovers DVL2 complexes with functional importance for Wnt/β-catenin signaling. Moreover, we provide evidence that DVL2 condensates form in two steps by pre-oligomerization via high-affinity interaction sites, such as LCR4, and subsequent condensation via low-affinity interaction sites, such as CD2.

Endogenous oligomer formation underlies DVL2 condensates and promotes Wnt/β-catenin signaling.

Activation of the Wnt/β-catenin pathway crucially depends on the polymerization of dishevelled 2 (DVL2) into biomolecular condensates. However, given the low affinity of known DVL2 self-interaction sites and its low cellular concentration, it is unclear how polymers can form. Here, we detect oligomeric DVL2 complexes at endogenous protein levels in human cell lines, using a biochemical ultracentrifugation assay. We identify a low-complexity region (LCR4) in the C-terminus whose deletion and fusion decreased and increased the complexes, respectively. Notably, LCR4-induced complexes correlated with the formation of microscopically visible multimeric condensates. Adjacent to LCR4, we mapped a conserved domain (CD2) promoting condensates only. Molecularly, LCR4 and CD2 mediated DVL2 self-interaction via aggregating residues and phenylalanine stickers, respectively. Point mutations inactivating these interaction sites impaired Wnt pathway activation by DVL2. Our study discovers DVL2 complexes with functional importance for Wnt/β-catenin signaling. Moreover, we provide evidence that DVL2 condensates form in two steps by pre-oligomerization via high-affinity interaction sites, such as LCR4, and subsequent condensation via low-affinity interaction sites, such as CD2.

Synthetic molecular cage receptors for carbohydrate recognition.

A captivating challenge in chemistry lies in achieving robust and precise binding of uncharged, hydrophilic carbohydrate entities. Although past decades have provided a variety of excellent molecular architectures tailored for carbohydrate recognition, including acyclic receptors, macrocycles and foldamers, recent advances have highlighted the potential of synthetic molecular cages. These structures are equipped with intricately designed cavities that contain bespoke noncovalent binding sites for carbohydrate interactions. Constructed with the principles of complementarity and preorganization, these cage receptors demonstrate high affinity and exquisite selectivity in carbohydrate recognition through noncovalent interactions, capitalizing on multivalency and cooperativity. This Review highlights recent advances in the design and application of molecular cages with diverse structures, interactions and binding capacities for carbohydrate recognition. In the concluding remarks, we discuss future avenues for further exploration.

Rationally Designed Binder with Polysulfide-Affinitive Moieties and Robust Network Structures for Improved Polysulfide Trapping and Structural Stability of Sulfur Cathode.

Lithium-sulfur batteries (LSBs) have emerged as a promising next-generation energy storage application owing to their high specific capacity and energy density. However, inherent insulating property of sulfur, along with its significant volume expansion during cycling, and shuttling behavior of lithium-polysulfides (LiPSs), hinder their practical application. To overcome these issues, a crosslinked cationic waterborne polyurethane (CCWPU) is rationally designed as a binder for LSBs. The mechanical robustness of CCWPU enables it to withstand the high stress derived from volume expansion of sulfur, facilitating charge-transferring through conserved charge-transfer pathway and promoting interconversion of LiPSs. Additionally, polar urethane groups offer favorable interaction sites with LiPSs, mitigating shuttling behavior of LiPSs via polar-polar interaction. Density functional theory investigations further elucidate that the incorporation of cationic moieties enhances LiPSs immobilization by confining Sn x- (x = 1 or 2) in LiPSs, thereby improving sulfur utilization. Benefiting from these, the cell with CCWPU demonstrates reduced polarization, superior LiPSs conversion rates, and stable cycling performance. Moreover, water-processable nature of CCWPU aligns with environmental consciousness. These diverse functionalities of CCWPU provide valuable insights for the development of advanced binder for LSBs, ultimately improving the electrochemical performances of LSBs.

Synthesis, Biological Evaluation, and Computational Studies of Schiff's Base Derivatives of 4-(4-Amino-5-Mercapto-4H-1,2,4-Triazol-3-Yl)Benzenesulfonamide as Cathepsin B Inhibitors.

A library of benzenesulfonamide incorporated Schiff's base derivatives of 4-amino-5-mercapto-1,2,4-triazoles 1a-f, 2a-e, and 3a-e has been synthesized and evaluated in-vitro for their inhibition potential against cathepsin B enzyme. All the tested compounds possessed good to excellent anti-cathepsin B activity (40.62%-74.36%) at 10-7m concentrations in comparison with the curcumin (51.20%) taken as reference. Among all, compound 3c has shown the highest activity exhibiting 74.36% inhibition followed by 3e and 3b (69.99% and 68.36% inhibition, respectively). Molecular docking was performed for the most active compound 3c and the reference compound, curcumin, to know their interactions in the active site of the target enzyme and the results obtained were in agreement with the experimental values. Additionally, DFT calculations were also performed to determine the values of electronic parameters including energies of highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), HOMO-LUMO energy gap, chemical hardness, chemical softness, chemical potential, electronegativity, and electrophilicity index.

Protein-Variant-Phenotype Study of NBAS Using AlphaFold in the Aspect of SOPH Syndrome.

NBAS gene variants cause phenotypically distinct and nonoverlapping conditions, SOPH syndrome and ILFS2. NBAS is a so-called "moonlighting" protein responsible for retrograde membrane trafficking and nonsense-mediated decay. However, its three-dimensional model and the nature of its possible interactions with other proteins have remained elusive. Here, we used AlphaFold to predict protein-protein interaction (PPI) sites and mapped them to NBAS pathogenic variants. We repeated in silico milestone studies of the NBAS protein to explain the multisystem phenotype of its variants, with particular emphasis on the SOPH variant (p.R1914H). We revealed the putative binding sites for the main interaction partners of NBAS and assessed the implications of these binding sites for the subdomain architecture of the NBAS protein. Using AlphaFold, we disclosed the far-reaching impact of NBAS variants on the development of each phenotypic trait in patients with NBAS-related pathologies.

Constructing Predictive Implicit Solvent Models: Insights from Exploring Potential Parameter Space and Property Predictions.

Implicit solvent (IS) models enhance the efficiency of simulating liquid systems, but those based on the potential of mean force calculations using explicit solvent (ES) models often fail to capture the solute structure and assembly dynamics under various conditions. This study examines the relationships between the parameter space of IS models and their predictive capabilities regarding solute structure and assembly dynamics, focusing on NaCl solutions and protein-bound silica colloidal nanoparticles. For NaCl solutions, models developed using concentration-dependent dielectric constants generally lack efficacy, and their effectiveness in predicting high-concentration liquid structures varies based on the ES model used. Adjusting the dielectric constant value or the shape of the short-range potentials can improve the accuracy of these models in predicting liquid structures. For protein-bound silica colloidal nanoparticles, we find that interaction site size and model resolution significantly influence the prediction of nanoparticle assembly dynamics, with different resolutions producing aggregates with distinct structures and connection modes. This study elucidates the complex relationship between parameter space in IS models and liquid structure and assembly kinetics, providing crucial insights for developing more accurate and predictive models.

Historical Bird Atlas and Contemporary Citizen Science Data Reveal Long‐Term Changes in Geographic Range of Kenyan Birds

ABSTRACTAimHistorical bird atlases provide comprehensive datasets for investigating long‐term changes in species' distribution. In the context of accelerating biodiversity loss, these datasets can lend critical insights into the state of bird distributions across broad spatio‐temporal scales and provide much‐needed information for impactful conservation. In Africa, the potential of atlas data to understand changes in avian populations remains largely untapped.LocationThis study mapped changes in national distribution patterns of 1088 bird species found in Kenya.MethodsTapping into one of the earliest atlas databases, this study compared Kenyan bird atlas data collected between 1970 and 1984 with recent citizen science data sourced from the Kenya Bird Map project and eBird to determine changes in ranges across 50 years. We produced maps displaying, for every 27 × 27 km square of the country, whether a species appeared, was present throughout both periods, or disappeared. We account for the change in data collection effort between the two periods by quantifying the confidence of the change for each square.ResultsThe maps produced for each species are publicly accessible through an interactive website: https://kenyabirdtrends.co.ke/. We found that related species tended to experience similar changes in their distribution ranges. The ranges of Palearctic migrants and scavengers declined drastically, while introduced birds experienced a significant range increase over the past 50 years.Main ConclusionsThis study demonstrates the potential of integrating recent citizen science data with historical atlas data to draw out the changes in range for all species at national level. The range contraction of Palearctic migrants and scavengers echoed corresponding drops in abundance at local, regional and global scales. These findings lend additional weight to the need for an increased conservation focus on migratory and scavenging birds in Kenya.

Research and Modeling of Commercial Location Selection Based on Geographic Big Data and Mobile Signaling Data—A Case Study of the Central Urban Area of Beijing

The layout and site selection strategy of commercial facilities are crucial for both enterprise performance and market image, while also significantly impacting the overall planning of urban commercial environments. However, conventional methods of choosing sites sometimes depend on outdated management information systems or static statistical models, which may not take into account all relevant factors and have poor data quality. By utilizing geographical big data and geographical artificial intelligence, this study improves the viability of commercial layout and site selection methods. This study utilizes mobile phone signaling data from Beijing combined with point-of-interest (POI) data from within the Sixth Ring Road of Beijing to identify user behaviors using algorithms. Through a combination of BiLSTM-RF and reinforcement learning algorithms, a population location prediction algorithm is constructed to address the issues of inaccurate and outdated population flow data in commercial site selection. The forecast distribution has a high level of accuracy, with a prediction accuracy rate of 73.2%. Additionally, based on geographical big data, the urban landscape is reconstructed to create a 3D model of Beijing. An immersive interactive commercial site selection system is implemented using the Unreal Engine.

Combinatorial Targeting of Common Docking and ATP Binding Sites on Mps1 MAPK for Management of Pathogenic Fungi.

Resistance in pathogenic fungi necessitates the development of fungicides with new mechanisms of action. The Mps1 MAPK of Magnaporthe oryzae, the pathogen of rice blast disease, has been shown to be a molecular target for fungicide research. Here, we present compound TAK-733 that interacts with the common docking (CD) site of Mps1 and can be used in combination with ATP-competitive inhibitors. We initially identified compounds PLX-4720 and TAK-733 that interact with Mps1. Subsequent assays show that PLX-4720 is an ATP-competitive inhibitor, whereas TAK-733 binds to the CD site of Mps1─an interaction site for its MAPKK─but not to the ATP-binding pocket as it does in the kinase MEK1. In vivo assays demonstrated that TAK-733 exhibits combinational effects with ATP-competitive inhibitors PLX-4720 and A378-0. Collectively, we present TAK-733 as having a new mechanism of action suitable for combinational application with ATP-competitive inhibitors in the management of pathogenic fungi.

The gut microbiota-derived metabolite indole-3-propionic acid enhances leptin sensitivity by targeting STAT3 against diet-induced obesity.

Obesity is associated with the gut microbiome. Here, we report that gut commensal Clostridia bacteria regulate host energy balance through the tryptophan-derived metabolite indole-3-propionic acid (IPA). IPA acts as an endogenous leptin sensitiser to counteract obesity. Mechanistically, IPA is secreted from the gut into the circulation, and then targets to the STAT3 in the hypothalamic appetite regulation centre, promoting its phosphorylation and nuclear translocation, which enhances the body's response to leptin, and regulates the balance between appetite and energy metabolism. The in vitro pull-down assays involving site-directed mutagenesis demonstrate that Trp623 in the SH2 domain is the key binding site for STAT3-IPA interaction. High-fat diet (HFD), rather than genetic factors, induces excessive secretion of antimicrobial peptides by Paneth cells, inhibiting the growth of Clostridia in the gut and resulting in decreased production of the beneficial metabolite IPA. IPA or Clostridium sporogenes supplement effectively controls weight gain, improves glucose metabolism, and reduces inflammation in DIO mice. IPA fails to achieve such effects in ob/ob mice, while exogenous leptin administration restores the therapeutic effect of IPA. Our study suggests that the IPA-based gut-brain axis regulates host metabolism, and supplementation with microbiome-derived IPA could be a promising intervention strategy for treating obesity.

The mechanism of DEHP-induced lipid accumulation in liver of female zebrafish

Diethylhexyl phthalate (DEHP) is a typical environmental pollutant and poses a potential threat to organisms by disrupting the lipid metabolism. This study found that DEHP at environmental concentrations, led to lipid accumulation in female zebrafish, as indicated by significant increases in the content of total cholesterol, triglycerides and the lipid droplets, in a concentration-dependent manner. However, how DEHP induces the lipid accumulation remains poorly understood. Our results demonstrated that DEHP up-regulated the expression of fat synthesis related-genes fas, acc, acs, elvol6, scd and dgat1, and increased the enzymatic activity of fatty acid synthase and acetyl-CoA carboxylase. Furthermore, the expression of several key transcription factors that regulate fat synthesis was detected, among which active sterol regulatory element-binding protein-1 (SREBP-1) was significantly increased. When active SREBP-1 was inhibited with specific inhibitor or knocked down by transient transfection, the expression of lipid synthesis-related genes was significantly decreased in DEHP group, indicating that DEHP disrupted the lipid synthesis via SREBP-1 pathway. Additionally, molecular docking revealed direct interaction sites between DEHP and SREBP-1. Our findings revealed that DEHP could directly activate SREBP-1-mediated lipid synthesis, providing theoretical basis for DEHP threatening biological health.

GACT-PPIS: Prediction of protein-protein interaction sites based on graph structure and transformer network

The prediction of protein-protein interaction sites (PPIS) is currently crucial for regulating many biological activities in cells and developing drugs for various diseases. Deep learning-based methods have been proposed for predicting PPIS, significantly reducing the manpower and time costs associated with traditional experimental methods such as yeast two-hybrid, mass spectrometry, and affinity purification. However, the predictive accuracy of these deep learning methods has not yet reached the expected level. Therefore, we introduce a model called GACT-PPIS.The design of the GACT-PPIS algorithm aims to utilize combined information from protein sequences and structures as input to predict protein-protein interaction sites. The core of GACT-PPIS utilizes an Enhanced Graph Attention Network (EGAT) with initial residual and identity mappings, along with a deep Transformer network as the basic units, supplemented by Graph Convolutional Networks (GCN), effectively aggregating information from neighboring nodes for each node. After multiple network layers, the information of the entire protein is also fused into the nodes, and the Transformer network further enhances the model's performance.Experimental results show that GACT-PPIS outperforms the most representative models in terms of Recall, F1-measure, MCC, AUROC, and AUPRC on the benchmark test set (Test-60). Additionally, on other independent test sets (UBTest-31-6), GACT-PPIS leads in terms of Accuracy, Precision, Recall, F1-measure, MCC, AUROC, and AUPRC compared to the most representative models. It is worth noting that GACT-PPIS demonstrates excellent generalization and versatility across different test sets, showcasing good performance on multiple test sets for the same trained GACT-PPIS model.

Pseudohalogen regulation of benzimidazole small molecule acceptor to optimize molecular crystallinity in Q-PHJ organic solar cells

The cyano group is a pseudohalogen with chemical properties similar to halogens. It has the ability to regulate the stacking and energy levels of molecules in organic solar small molecule non-fullerene acceptor materials. In this study, we introduce two novel alkylated derivatives, BMIC-CN-Me and BMIC-CN-iPr, featuring a cyano-modified benzimidazole core. This central nucleus design is reported for the first time, offering a unique approach to molecular engineering in organic photovoltaics. BMIC-CN-Me, in particular, enhances device performance by meticulously managing molecular stacking through steric hindrance. Analysis via single-crystal X-ray diffraction reveals five distinct stacking modes, with an average intermolecular distance of approximately 3.31 Å, optimizing the efficiency of charge transfer. This precise molecular arrangement elevates the photoconversion efficiency (PCE) of the non-fullerene acceptor, based on the benzimidazole core, to an impressive 17.6 %. Moreover, the material demonstrates exceptional stability, retaining over 80 % of its initial efficiency after 1200 h in a glove box and maintaining more than 80 % of its original efficiency after 500 h of continuous simulated solar irradiation. Compared to the 2-methylimidazole-derived molecules acceptor, devices prepared using BMIC-CN-Me demonstrate superior performance due to their better-matched energy levels and UV–Vis absorption spectrum. Furthermore, when contrasted with BMIC-CN-iPr, BMIC-CN-Me exhibits a more tightly packed molecular arrangement. These factors contribute to more effective exciton dissociation, accelerated charge transport, and the suppression of recombination, leading to an enhanced fill factor and overall photoelectric conversion efficiency. The quasi-planar heterojunction architecture further bolsters device stability. The cyano-modified benzimidazole structure provides additional non-covalent interaction sites, which augment the material’s stability. Our findings indicate that the cyano substitution of the benzimidazole core not only enhances material stability and molecular aggregation but also significantly improves the performance of organic solar cells. This innovative approach to molecular design holds promise for the development of high-performing and durable organic photovoltaic materials.

Evaluation of aspartame as a co-former in the preparation of co-amorphous formulations of dipyridamole using spray drying

Co-amorphous systems (CAMs) have shown promise in addressing the challenges associated with poorly water-soluble drugs. However, the limited selection of co-formers and the use of lab-scale techniques for their preparation present challenges in fully utilizing the advantages of CAMs. In this study, we used aspartame (a methyl ester of the aspartic acid/phenylalanine) as a model dipeptide with the BCS class II drug dipyridamole, to prepare co-amorphous systems using spray drying. The feed solutions were prepared by dissolving the drug and co-former into methanol–water mixtures. The spray drying process was evaluated and solid-state properties were compared with those of the individual amino acids, amino acid mixtures and aspartame as co-formers. Co-amorphous systems prepared with aspartame (AspPhe) exhibited better solid-state properties, including a higher glass transition temperature (Tg), compared to the individual amino acids and the mixture of amino acids. Additionally, this formulation showed improved physical stability when stored at 25 °C/60 % RH conditions. Hirshfeld Surface (HS) analysis was employed to visualize and analyse the molecular interaction sites within the crystal structures of dipyridamole and aspartame. The observed interactions were then correlated with the molecular interactions identified through FT-IR spectroscopic analysis within the CAMs. The spectroscopic analysis revealed molecular interactions between the sites found at the shortest distances in the HS analysis. The dominant hydrogen bond interactions identified in the co-amorphous DPM-AspPhe system was found to contribute significantly to its improve stability. X-ray powder diffraction in non-ambient mode reveals that both temperature and humidity play a role in the crystallization of the co-amorphous DPM-AspPhe. Crystallization rates increased notably at high temperature and humidity. To predict stability under accelerated conditions, the crystallization rates from DPM-AspPhe were fitted to a modified Arrhenius equation. However, the predictive accuracy of the resulting model was limited to a specific range of conditions.

Exploring wide gap semiconductor characteristics in -pinene crystals: insights from density functional theory.

-Pinene, a bicyclic monoterpene found extensively in the essential oils of conifers, has shown potential in pharmacological applications. This study theoretically investigates the structural and electronic properties of the (1S)- - -pinene crystal, focusing on its potential for nanoelectronic applications due to the observed wide band gap. Structural analysis revealed that the crystal's unit cell contains 104 atoms with orthorhombic symmetry, and its lattice parameters show excellent agreement with experimental data. Electronic analysis indicated an indirect band gap of 3.58 eV for LDA-PZ and 4.32 eV for GGA-PBE, suggesting that (1S)- - -pinene behaves as a wide band-gap semiconductor. The electronic structure is primarily influenced by contributions from the orbitals of Carbon atoms and the s orbital of Hydrogen atoms, highlighting potential sites for chemical interaction. DFT calculations were performed using the Quantum Espresso software. They employed both the local density approximation (LDA-PZ) and the generalized gradient approximation (GGA-PBE), parameterized by the Perdew-Burke-Ernzerhof exchange-correlation functional. Norm-conserving pseudopotentials were applied to represent the core electrons accurately.

Understanding the Structural Modulations in Twisted Donor-Acceptor-Donor (D-A-D) Systems for Boosting Type I Photosensitizing Photocatalytic Activity.

Supramolecular assemblies based on the twisted donor-acceptor-donor (D-A-D) building block Qx-Ind have been developed, which interestingly, due to the balanced angle of twist (38.28°), high intermolecular charge transfer, and crystallization induced emission (CIE) characteristics, exhibit high molar absorptivity and a long-lived "lighted" excited state at the supramolecular level. The validity of the design concept was examined by preparing CIE active D-A-D system Qx-Indaz (weak donor, low angle of twist: 35.45°), in which, due to the insertion of an additional binding site for noncovalent interactions, a drastic change in the photophysical behavior is observed. The combined spectroscopic studies of all the compounds unveil the strong impact of modulation of the angle of twist and intermolecular charge transfer upon photophysical behavior in the aggregated state. Due to the favorable photophysical behavior, the supramolecular assemblies of Qx-Ind exhibit high type I photosensitizing activity in comparison to Qx-Indaz. The superior type I photosensitizing activity of Qx-Ind assemblies is manifested in their ability to efficiently catalyze the aerobic oxidative synthesis of quinazolin-4(3H)-ones (via type I ROS) from 2-aminobenzamide and aromatic aldehydes in the absence of additional additives (base/oxidant). Unlike photocatalytic nanoassemblies reported in the literature, due to the CIE characteristics, Qx-Ind does not require preliminary preparation and could be directly introduced in the solid state to reaction media. Thus, the present work demonstrates a simple strategy of upgrading type I photosensitizing activity by improving the ground/excited state behavior of a twisted D-A-D system through modulation of the angle of twist and charge transfer characteristics.

In Silico Evaluation of Some Computer-Designed Fluoroquinolone–Glutamic Acid Hybrids as Potential Topoisomerase II Inhibitors with Anti-Cancer Effect

Background/Objectives: Fluoroquinolones (FQs) are topoisomerase II inhibitors with antibacterial activity, repositioned recently as anti-cancer agents. Glutamic acid (GLA) is an amino acid that affects human metabolism. Since an anti-cancer mechanism of FQs is human topoisomerase II inhibition, it is expected that FQ-GLA hybrids can act similarly. Methods: We designed 27 hypothetical hybrids of 6 FQs and GLA through amide bonds at the 3- and 7-position groups of FQs or via ethylenediamine/ethanolamine linkers at the carboxyl group of the FQ. Hydroxamic acid derivatives were also theoretically formulated. Computational methods were used to predict their physicochemical, pharmacokinetic, or toxicological properties and their anti-cancer activity. For comparison, etoposide was used as an anti-cancer agent inhibiting topoisomerase II. Molecular docking assessed whether the hybrids could interact with the human topoisomerase II beta in the same binding site and interaction sites as etoposide. Results: All the hybrids acted as potential topoisomerase II inhibitors, demonstrating possible anti-cancer activity on several cancer cell lines. Among all the proposed hybrids, MF-7-GLA would be the ideal candidate as a lead compound. The hybrid OF-3-EDA-GLA and the hydroxamic acid derivatives also stood out. Conclusions: Both FQs and GLA have advantageous structures for obtaining hybrids with favourable properties. Improvements in the hybrids’ structure could lead to promising results.

Consortium of ‘consistent amino acid substitutions’ on influenza A (H1N1) viral proteins emerged at specific stages of viral infection: a big data analysis

Influenza A (H1N1) virus has been one of the most common threats to humankind since 1918. The viral genome is frequently substituted, leading to new strains and recurrent pandemics. Despite knowing the effects of single amino acid substitutions on individual viral proteins, the effects of collective substitutions on viral infection remain elusive. Here, we addressed whether the ‘consistent amino acid substitutions’ occur in a consortium on functional domains and protein-protein interaction (PPI) sites, impacting overall viral infection and host immune responses. By definition, ‘consistent substitutions’ occur on ‘all’ the Influenza A (H1N1) viral strains isolated in a particular year. To address this question, big protein data (563370 sequences and 9824 PPI) were analysed using multiple sequence alignment, text mining, protein structure analyses etc. A total of one hundred and five ‘consistent substitutions’ were mapped on the ten viral proteins of influenza A(H1N1) pdm09 strain. Fifty of those emerged on viral protein functional domains and PPIs, engaged in the specific stages of the viral infection, namely, i) cell surface entry and exit, ii) nuclear import, vRNP assembly, and nuclear export, and iii) antagonizing immune responses. For the first time, the study showed that a consortium of ‘consistent substitutions’ emerged on protein functional domains and PPIs, impacting specific stages of viral infection rather than a single protein and presumably navigating viral escape from human immune response.

Achieving Uniform Deposition of Zn with Amide Additives for Metal Anodes Stabilization.

The practical applications of aqueous zinc-ion batteries (AZIBs) are hindered by detrimental effects such as dendrites formation at the Zn metal anode interface and parasitic side reactions induced by H2O. Hence, we propose adding amide additives to the Zn sulfate electrolyte (ZSO) to regulate the composition and properties of the electrolytes, thereby stabilizing the Zn anode interface. Different amide molecules containing formamide (FA), acetamide (AA), or trifluoroacetamide (TFA) are discussed. The polar C═O group shared by amide molecules can interact with Zn2+, forming their solvation shells. The molecules can also facilitate the transport of Zn2+ and increase the conductivity of the electrolytes. Additionally, amide molecules can interact with H2O through hydrogen bonds to limit the erosion of active H2O on the Zn anode. The unique -H, -CH3, and -CF3 groups of the molecules result in different polarities and varying numbers of interaction sites with H2O and Zn2+, leading to some differences in the protective effects of the Zn anode. The stability and lifespan of Zn||Zn batteries assembled with amide electrolytes have significantly improved, especially those with TFA. Moreover, the Zn||NH4V4O10 full cells demonstrate remarkable capacity retention, and the overall performance of the batteries has also been enhanced.