QTY code designed antibodies for aggregation prevention: A structural bioinformatic and computational study.

Therapeutic monoclonal antibodies are the most rapidly growing class of molecular medicine, and they are beneficial to the treatment of a broad spectrum of human diseases. However, the aggregation of antibodies during the process of manufacture, distribution, and storage poses significant challenges, potentially compromising efficacy and inducing adverse immune responses. We previously conceived a QTY (glutamine, threonine, tyrosine) code, a simple tool for enhancing protein water-solubility by systematically pairwise replacing hydrophobic residues L (leucine), V (valine)/I (isoleucine), and F (phenylalanine). The QTY code offers a promising alternative to traditional methods of controlling aggregation in integral transmembrane proteins. In this study, we designed variants of four antibodies applying the QTY code, changing only the ß-sheets. Through the structure-based aggregation analysis, we found that these QTY antibody variants demonstrated significantly decreased aggregation propensity compared to their wild-type counter parts. Our results of molecular dynamics simulations showed that the design by QTY code is capable of maintaining the antigen-binding affinity and structural stability. Our structural informatic and computational study suggests that the QTY code offers a significant potential in mitigating antibody aggregation.

APETALA2/ethylene-responsive factors in higher plant and their roles in regulation of plant stress response.

Plants, anchored throughout their life cycles, face a unique set of challenges from fluctuating environments and pathogenic assaults. Central to their adaptative mechanisms are transcription factors (TFs), particularly the AP2/ERF superfamily-one of the most extensive TF families unique to plants. This family plays instrumental roles in orchestrating diverse biological processes ranging from growth and development to secondary metabolism, and notably, responses to both biotic and abiotic stresses. Distinguished by the presence of the signature AP2 domain or its responsiveness to ethylene signals, the AP2/ERF superfamily has become a nexus of research focus, with increasing literature elucidating its multifaceted roles. This review provides a synoptic overview of the latest research advancements on the AP2/ERF family, spanning its taxonomy, structural nuances, prevalence in higher plants, transcriptional and post-transcriptional dynamics, and the intricate interplay in DNA-binding and target gene regulation. Special attention is accorded to the ethylene response factor B3 subgroup protein Pti5 and its role in stress response, with speculative insights into its functionalities and interaction matrix in tomatoes. The overarching goal is to pave the way for harnessing these TFs in the realms of plant genetic enhancement and novel germplasm development.

Theoretical Analysis of Selectivity Differences in Ketoreductases toward Aldehyde and Ketone Carbonyl Groups.

Lactobacillus kefir alcohol dehydrogenase (LkADH) and ketoreductase from Chryseobacterium sp. CA49 (ChKRED12) exhibit different chemoselectivity and stereoselectivity toward a substrate with both keto and aldehyde carbonyl groups. LkADH selectively reduces the keto carbonyl group while retaining the aldehyde carbonyl group, producing optically pure R-alcohols. In contrast, ChKRED12 selectively reduces the aldehyde group and exhibits low reactivity toward ketone carbonyls. This study investigated the structural basis for these differences and the role of specific residues in the active site. Molecular dynamics (MD) simulations and quantum chemical calculations were used to investigate the interactions between the substrate and the enzymes and the essential cause of this phenomenon. The present study has revealed that LkADH and ChKRED12 exhibit significant differences in the structure of their respective active pockets, which is a crucial determinant of their distinct chemoselectivity toward the same substrate. Moreover, residues N89, N113, and E144 within LkADH as well as Q151 and D190 within ChKRED12 have been identified as key contributors to substrate stabilization within the active pocket through electrostatic interactions and van der Waals forces, followed by hydride transfer utilizing the coenzyme NADPH. Furthermore, the enantioselectivity mechanism of LkADH has been elucidated using quantum chemical methods. Overall, these findings not only provide fundamental insights into the underlying reasons for the observed differences in selectivity but also offer a detailed mechanistic understanding of the catalytic reaction.

Genome-Wide Identification of the WRKY Gene Family and Functional Characterization of CpWRKY5 in Cucurbita pepo.

The WRKY gene family is crucial for regulating plant growth and development. However, the WRKY gene is rarely studied in naked kernel formation in hull-less Cucurbita pepo L. (HLCP), a natural mutant that lacks the seed coat. In this research, 76 WRKY genes were identified through bioinformatics-based methods in C. pepo, and their phylogenetics, conserved motifs, synteny, collinearity, and temporal expression during seed coat development were analyzed. The results showed that 76 CpWRKYs were identified and categorized into three main groups (I-III), with Group II further divided into five subgroups (IIa-IIe). Moreover, 31 segmental duplication events were identified in 49 CpWRKY genes. A synteny analysis revealed that C. pepo shared more collinear regions with cucumber than with melon. Furthermore, quantitative RT-PCR (qRT-PCR) results indicated the differential expression of CpWRKYs across different varieties, with notable variations in seed coat development between HLCP and CP being attributed to differences in CpWRKY5 expression. To investigate this further, CpWRKY5-overexpression tobacco plants were generated, resulting in increased lignin content and an upregulation of related genes, as confirmed by qRT-PCR. This study offers valuable insights for future functional investigations of CpWRKY genes and presents novel information for understanding the regulation mechanism of lignin synthesis.

Dynamic Interplay between Microbiota Shifts and Differential Metabolites during Dairy Processing and Storage.

Due to the intricate complexity of the original microbiota, residual heat-resistant enzymes, and chemical components, identifying the essential factors that affect dairy quality using traditional methods is challenging. In this study, raw milk, pasteurized milk, and ultra-heat-treated (UHT) milk samples were collectively analyzed using metagenomic next-generation sequencing (mNGS), high-throughput liquid chromatography-mass spectrometry (LC-MS), and gas chromatography-mass spectrometry (GC-MS). The results revealed that raw milk and its corresponding heated dairy products exhibited different trends in terms of microbiota shifts and metabolite changes during storage. Via the analysis of differences in microbiota and correlation analysis of the microorganisms present in differential metabolites in refrigerated pasteurized milk, the top three differential microorganisms with increased abundance, Microbacterium (p < 0.01), unclassified Actinomycetia class (p < 0.05), and Micrococcus (p < 0.01), were detected; these were highly correlated with certain metabolites in pasteurized milk (r > 0.8). This indicated that these genera were the main proliferating microorganisms and were the primary genera involved in the metabolism of pasteurized milk during refrigeration-based storage. Microorganisms with decreased abundance were classified into two categories based on correlation analysis with certain metabolites. It was speculated that the heat-resistant enzyme system of a group of microorganisms with high correlation (r > 0.8), such as Pseudomonas and Acinetobacter, was the main factor causing milk spoilage and that the group with lower correlation (r < 0.3) had a lower impact on the storage process of pasteurized dairy products. By comparing the metabolic pathway results based on metagenomic and metabolite annotation, it was proposed that protein degradation may be associated with microbial growth, whereas lipid degradation may be linked to raw milk's initial heat-resistant enzymes. By leveraging the synergy of metagenomics and metabolomics, the interacting factors determining the quality evolution of dairy products were systematically investigated, providing a novel perspective for controlling dairy processing and storage effectively.

pH-Responsive Protein Conformation Transistor.

Analogous to electronic transistors, transistor-like responsive materials undergo sharp structural transitions in response to a very narrow range of microenvironment signals. This kind of material is typically limited to synthetic polymer-derived nanoscale assembly or disassembly and has profound implications for modern high-tech applications. Herein, we evolve this system from synthetic polymers to biopolymers and extend the corresponding assembly scale from the nanoscale to meso/macro-scale. We develop unique protein nanocrystals with core-shell structures through a two-step nucleation process. The protein nanocrystals exhibit exceptional transistor-like pH-responsive mesoscale assembly through the formation of inter-particle ß-sheet linkers. This allows ultrasensitive cross-linking behavior, such as self-coacervation at a water/water interface, ultrafast gelation in seconds, and ultrasensitive swelling for detection of basic vapors at extremely low concentrations. This breakthrough has great promise for broader applications such as drug encapsulation and delivery, biosensing, cytomimetic materials, and microfluidic chemistry.

CrMP-Sol database: classification, bioinformatic analyses and comparison of cancer-related membrane proteins and their water-soluble variant designs.

Membrane proteins are critical mediators for tumor progression and present enormous therapeutic potentials. Although gene profiling can identify their cancer-specific signatures, systematic correlations between protein functions and tumor-related mechanisms are still unclear. We present here the CrMP-Sol database ( https://bio-gateway.aigene.org.cn/g/CrMP ), which aims to breach the gap between the two. Machine learning was used to extract key functional descriptions for protein visualization in the 3D-space, where spatial distributions provide function-based predictive connections between proteins and cancer types. CrMP-Sol also presents QTY-enabled water-soluble designs to facilitate native membrane protein studies despite natural hydrophobicity. Five examples with varying transmembrane helices in different categories were used to demonstrate the feasibility. Native and redesigned proteins exhibited highly similar characteristics, predicted structures and binding pockets, and slightly different docking poses against known ligands, although task-specific designs are still required for proteins more susceptible to internal hydrogen bond formations. The database can accelerate therapeutic developments and biotechnological applications of cancer-related membrane proteins.

Dynamic Dimerization of Chemokine Receptors and Potential Inhibitory Role of Their Truncated Isoforms Revealed through Combinatorial Prediction.

Chemokine receptors play crucial roles in fundamental biological processes. Their malfunction may result in many diseases, including cancer, autoimmune diseases, and HIV. The oligomerization of chemokine receptors holds significant functional implications that directly affect their signaling patterns and pharmacological responses. However, the oligomerization patterns of many chemokine receptors remain poorly understood. Furthermore, several chemokine receptors have highly truncated isoforms whose functional role is not yet clear. Here, we computationally show homo- and heterodimerization patterns of four human chemokine receptors, namely CXCR2, CXCR7, CCR2, and CCR7, along with their interaction patterns with their respective truncated isoforms. By combining the neural network-based AlphaFold2 and physics-based protein-protein docking tool ClusPro, we predicted 15 groups of complex structures and assessed the binding affinities in the context of atomistic molecular dynamics simulations. Our results are in agreement with previous experimental observations and support the dynamic and diverse nature of chemokine receptor dimerization, suggesting possible patterns of higher-order oligomerization. Additionally, we uncover the strong potential of truncated isoforms to block homo- and heterodimerization of chemokine receptors, also in a dynamic manner. Our study provides insights into the dimerization patterns of chemokine receptors and the functional significance of their truncated isoforms.

Unique regulator SrpR mediates crosstalk between efflux pumps TtgABC and SrpABC in Pseudomonas putida B6-2 (DSM 28064).

The coexistence of multiple homologous resistance-nodulation-division (RND) efflux pumps in bacteria is frequently described with overlapping substrate profiles. However, it is unclear how bacteria balance their transcription in response to the changing environment. Here, we characterized a repressor, SrpR, in Pseudomonas putida B6-2 (DSM 28064), whose coding gene is adjacent to srpS that encodes the local repressor of the RND-type efflux pump SrpABC gene cluster. SrpR was demonstrated as a specific repressor of another RND efflux pump gene cluster ttgABC that is locally repressed by TtgR. SrpR was found to be capable of binding to the ttgABC operator with a higher affinity (KD , 138.0 nM) compared to TtgR (KD , 15.4 µM). EMSA and ß-galactosidase assays were performed to survey possible effectors of SrpR with 35 available chemicals being tested. Only 2,3,4-trichlorophenol was identified as an effector of SrpR. A regulation model was then proposed, representing a novel strategy for balancing the efflux systems with partially overlapping substrate profiles. This study highlights sophisticated interactions among the RND efflux pumps in a Pseudomonas strain, which may endow bacteria with certain advantages in a fluctuant environment.

A HER2 target antibody drug conjugate combined with anti-PD-(L)1 treatment eliminates hHER2+ tumors in hPD-1 transgenic mouse model and contributes immune memory formation.

PURPOSE: Disitamab vedotin (RC48) is an HER2-directed antibody-drug conjugate, emerging as an effective strategy for cancer therapy, which not only enhances antitumor immunity in previous animal models but also improves clinical outcomes for patients such as with gastric cancer, urothelium carcinoma, and HER2 low-expressing breast cancer. Here, we explore the combination therapeutic efficacy of this novel HER2-targeting ADC with immune checkpoint inhibitors in a human HER2-expressing syngeneic breast cancer model. METHODS: The human HER2+ cancer cell line is constructed by stable transfection and individual clones were isolated by single-cell sorting. Flow cytometry was performed to determine its binding activity. Cytotoxic effect was determined using an MTT assay with the supplement of RC48. Human PD-1 transgenic mice were used to analyze the in vivo antitumor effects of the ADC and its combination therapy with PD-1/PD-L1 antibody. RESULTS: The combination of RC48 and PD-1/PD-L1 immune checkpoint inhibition significantly enhanced tumor suppression and antitumor immunity. Tumor rejection in the synergistic groups was accompanied by massive T cell infiltration and immune marker activation. Furthermore, the combination therapy promoted immunological memory formation in the tumor eradication animals, protecting them from tumor rechallenge. CONCLUSION: A novel HER2-targeting ADC combined with immune checkpoint inhibitors can achieve remarkable effects in mice and elicit long-lasting immune protection in a hHER2+ murine breast cancer model. This study provides insights into the efficacy of RC48 therapeutic activity and a rationale for potential therapeutic combination strategies with immunotherapy.

Controlling the Structure and Function of Protein Thin Films through Amyloid-like Aggregation.

Protein thin films (PTFs) with tunable structure and function can offer multiple opportunities in various fields such as surface modification, biomaterials, packaging, optics, electronics, separation, energy, and environmental science. Although nature may offer a variety of examples of high-level control of structure and function, e.g., the S layer of cells, synthetic alternatives for large-area protein-based thin films with fine control over both biological function and material structure are a key challenge, especially when aiming for facile, low-cost, green, and large-scale preparation as well as a further extension of function, such as the encapsulation and release of functional building blocks.Therefore, regarding the structure and function of PTFs, we will first briefly comment on the problems associated with PTF fabrication, and then, regarding the basis of our long-term research on protein-based thin films, we will summarize the new strategies that we have developed in recent years to explore and control the structure and function of PTFs for frontier research and practical applications.Inspired by naturally occurring protein amyloid fibrillization, we proposed the amyloid-like protein aggregation strategy to assemble proteins into supramolecular 2D films with extremely large sizes and enduring interfacial adhesion stability. This approach opened a new window for PTF fabrication in which the spontaneous interfacial 2D aggregation of protein oligomers instead of traditional 1D protofibril elongation directs the assembly of proteins. As a result, the film morphology, thickness, porosity, and function can be tailored by simply tuning the interfacial aggregation pathways.We further modified amyloid-like protein aggregation to develop chemoselective reaction-induced protein aggregation (CRIPA). It is well known that chemoselective reactions have been employed for protein modification. However, the application of such reactions in PTF fabrication has been overlooked. We initiated this new strategy by employing thiol-disulfide exchange reactions. These reactions are chemoselective toward proteins containing specific disulfide bonds with high redox potentials, resulting in amyloid-like aggregation and thin film formation. Functional proteins with immunity to such reactions can be encapsulated in thin films and released on demand without a loss of activity, opening a new avenue for the development of functional PTFs and coatings.Finally, the resultant amyloid-inspired PTFs, as a new type of biomimetic materials, provide a good platform for integration with various biomedical functions. Here, the creation of bioactive surfaces on virtually arbitrary substrates by amyloid-like PTFs will be discussed, highlighting antimicrobial, antifouling, molecular separation, and interfacial biomineralization activities that exceed those of their native protein precursors and synthetic alternatives.

Synthetic acid stress-tolerance modules improve growth robustness and lysine productivity of industrial Escherichia coli in fermentation at low pH.

BACKGROUND: During fermentation, industrial microorganisms encounter multiple stresses that inhibit cell growth and decrease fermentation yields, in particular acid stress, which is due to the accumulation of acidic metabolites in the fermentation medium. Although the addition of a base to the medium can counteract the effect of acid accumulation, the engineering of acid-tolerant strains is considered a more intelligent and cost-effective solution. While synthetic biology theoretically provides a novel approach for devising such tolerance modules, in practice it is difficult to assemble stress-tolerance modules from hundreds of stress-related genes. RESULTS: In this study, we designed a set of synthetic acid-tolerance modules for fine-tuning the expression of multi-component gene blocks comprising a member of the proton-consuming acid resistance system (gadE), a periplasmic chaperone (hdeB), and reactive oxygen species (ROS) scavengers (sodB and katE). Directed evolution was used to construct an acid-responsive asr promoter library, from which four variants were selected and used in the synthetic modules. The module variants were screened in a stepwise manner under mild acidic conditions (pH 5-6), first by cell growth using the laboratory Escherichia coli strain MG1655 cultured in microplates, and then by lysine production performance using the industrial lysine-producing E. coli strain MG1655 SCEcL3 cultured first in multiple 10-mL micro-bioreactors, and then in 1.3-L parallel bioreactors. The procedure resulted in the identification of a best strain with lysine titer and yield at pH 6.0 comparable to the parent strain at pH 6.8. CONCLUSION: Our results demonstrate a promising synthetic-biology strategy to enhance the growth robustness and productivity of E. coli upon the mildly acidic conditions, in both a general lab strain MG1655 and an industrial lysine-producing strain SCEcL3, by using the stress-responsive synthetic acid-tolerance modules comprising a limited number of genes. This study provides a reliable and efficient method for achieving synthetic modules of interest, particularly in improving the robustness and productivity of industrial strains.

Marker-Independent Food Identification Enabled by Combing Machine Learning Algorithms with Comprehensive GC × GC/TOF-MS.

Reliable methods are always greatly desired for the practice of food inspection. Currently, most food inspection techniques are mainly dependent on the identification of special components, which neglect the combination effects of different components and often lead to biased results. By using Chinese liquors as an example, we developed a new food identification method based on the combination of machine learning with GC × GC/TOF-MS. The sample preparation methods SPME and LLE were compared and optimized for producing repeatable and high-quality data. Then, two machine learning algorithms were tried, and the support vector machine (SVM) algorithm was finally chosen for its better performance. It is shown that the method performs well in identifying both the geographical origins and flavor types of Chinese liquors, with high accuracies of 91.86% and 97.67%, respectively. It is also reasonable to propose that combining machine learning with advanced chromatography could be used for other foods with complex components.

Repurposing fish waste into gelatin as a potential alternative for mammalian sources: A review.

Mammalian gelatin is extensively utilized in the food industry because of its physicochemical properties. However, its usage is restricted and essentially prohibited for religious people. Fish gelatin is a promising alternative with no religious and social restrictions. The desirable properties of fish gelatin can be significantly improved by various methods, such as the addition of active compounds, enzymes, and natural crosslinking agents (e.g., plant phenolics and genipin), and nonthermal physical treatments (e.g., ionizing radiation and high pressure). The aim of this study was to explore whether the properties of fish gelatin (gel strength, melting or gelling temperature, odor, viscosity, sensory properties, film-forming ability, etc.) could be improved to make it comparable to mammalian gelatin. The structure and properties of gelatins obtained from mammalian and fish sources are summarized. Moreover, the modification methods used to ameliorate the properties of fish gelatin, including rheological (gelling temperature from 13-19°C to 23-25°C), physicochemical (gel strengths from ∼200 to 250 g), and thermal properties (melting points from ∼25 to 30°C), are comprehensively discussed. The relevant literature reviewed and the technological advancements in the industry can propel the development of fish gelatin as a potential alternative to mammalian gelatin, thereby expanding its competitive market share with increasing utility.

Boosted Inner Surface Charge Transfer in Perovskite Nanodots@Mesoporous Titania Frameworks for Efficient and Selective Photocatalytic CO2 Reduction to Methane.

Exploring high-efficiency and stable halide perovskite-based photocatalysts for the selective reduction of CO2 to methane is a challenge because of the intrinsic photo- and chemical instability of halide perovskites. In this study, halide perovskites (Cs3 Bi2 Br9 and Cs2 AgBiBr6 ) were grown in situ in mesoporous TiO2 frameworks for an efficient CO2 reduction. Benchmarked CH4 production rates of 32.9 and 24.2 µmol g-1 h-1 with selectivities of 88.7 % and 84.2 %, were achieved, respectively, which are better than most reported halide perovskite photocatalysts. Focused ion-beam sliced-imaging techniques were used to directly image the hyperdispersed perovskite nanodots confined in mesopores with tunable sizes ranging from 3.8 to 9.9 nm. In situ X-ray photoelectronic spectroscopy and Kelvin probe force microscopy showed that the built-in electric field between the perovskite nanodots and mesoporous titania channels efficiently promoted photo-induced charge transfer. Density functional theory calculations indicate that the high methane selectivity was attributed to the Bi-adsorption-mediated hydrogenation of *CO to *HCO that dominates CO desorption.

Genetic mapping of highly versatile and solvent-tolerant Pseudomonas putida B6-2 (ATCC BAA-2545) as a 'superstar' for mineralization of PAHs and dioxin-like compounds.

Polycyclic aromatic hydrocarbons (PAHs) and dioxin-like compounds, including sulfur, nitrogen and oxygen heterocycles, are widespread and toxic environmental pollutants. A wide variety of microorganisms capable of growing with aromatic polycyclic compounds are essential for bioremediation of the contaminated sites and the Earth's carbon cycle. Here, cells of Pseudomonas putida B6-2 (ATCC BAA-2545) grown in the presence of biphenyl (BP) are able to simultaneously degrade PAHs and their derivatives, even when they are present as mixtures, and tolerate high concentrations of extremely toxic solvents. Genetic analysis of the 6.37 Mb genome of strain B6-2 reveals coexistence of gene clusters responsible for central catabolic systems of aromatic compounds and for solvent tolerance. We used functional transcriptomics and proteomics to identify the candidate genes associated with catabolism of BP and a mixture of BP, dibenzofuran, dibenzothiophene and carbazole. Moreover, we observed dynamic changes in transcriptional levels with BP, including in metabolic pathways of aromatic compounds, chemotaxis, efflux pumps and transporters potentially involved in adaptation to PAHs. This study on the highly versatile activities of strain B6-2 suggests it to be a potentially useful model for bioremediation of polluted sites and for investigation of biochemical, genetic and evolutionary aspects of Pseudomonas.

NBS-LRR Gene TaRPS2 is Positively Associated with the High-Temperature Seedling Plant Resistance of Wheat Against Puccinia striiformis f. sp. tritici.

Xiaoyan6 (XY6) is a wheat (Triticum aestivum) cultivar possessing nonrace-specific high-temperature seedling plant (HTSP) resistance against stripe rust, caused by Puccinia striiformis f. sp. tritici. Previously, we identified one particular gene, TaRPS2, for its involvement in the HTSP resistance. To elucidate the role of TaRPS2 in the HTSP resistance, we cloned the full length of TaRPS2 from XY6. The transcriptional expression of TaRPS2 was rapidly upregulated (19.11-fold) under the normal-high-normal temperature treatment that induces the HTSP resistance. The expression level of TaRPS2 in leaves was higher than that in the stems and roots. Quantification of the endogenous hormones in wheat leaves after P. striiformis f. sp. tritici inoculation showed that 1-aminocyclopropane-1-carboxylic acid, salicylic acid (SA), and jasmonic acid were involved in the HTSP resistance. In addition, detection of hydrogen peroxide (H2O2) accumulation indicated that reactive oxygen species burst was also associated with the HTSP resistance. Two hours after exogenous H2O2 treatment or 0.5 h after SA treatment, the expression level of TaRPS2 was increased by 2.66 and 2.35 times, respectively. The subcellular localization of enhanced green fluorescent protein-TaRPS2 fusion protein was in the nuclei and plasma membranes. Virus-induced gene silencing of TaRPS2 reduced the level of HTSP resistance in XY6. Compared with the nonsilenced leaves, the TaRPS2-silenced leaves had the reduction of necrotic cells but a greater number of uredinia. These results indicated that TaRPS2 positively regulates the HTSP resistance of XY6 against P. striiformis f. sp. tritici and is related to the SA and H2O2 signaling pathways.

QTY code enables design of detergent-free chemokine receptors that retain ligand-binding activities.

Structure and function studies of membrane proteins, particularly G protein-coupled receptors and multipass transmembrane proteins, require detergents. We have devised a simple tool, the QTY code (glutamine, threonine, and tyrosine), for designing hydrophobic domains to become water soluble without detergents. Here we report using the QTY code to systematically replace the hydrophobic amino acids leucine, valine, isoleucine, and phenylalanine in the seven transmembrane α-helices of CCR5, CXCR4, CCR10, and CXCR7. We show that QTY code-designed chemokine receptor variants retain their thermostabilities, α-helical structures, and ligand-binding activities in buffer and 50% human serum. CCR5QTY, CXCR4QTY, and CXCR7QTY also bind to HIV coat protein gp41-120. Despite substantial transmembrane domain changes, the detergent-free QTY variants maintain stable structures and retain their ligand-binding activities. We believe the QTY code will be useful for designing water-soluble variants of membrane proteins and other water-insoluble aggregated proteins.

Novel Bradykinin Receptor Inhibitors Inhibit Proliferation and Promote the Apoptosis of Hepatocellular Carcinoma Cells by Inhibiting the ERK Pathway.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Studies have shown that bradykinin (BK) is highly expressed in liver cancer. We designed the novel BK receptor inhibitors J051-71 and J051-105, which reduced the viability of liver cancer cells and inhibited the formation of cancer cell colonies. J051-71 and J051-105 reduced cell proliferation and induced apoptosis in HepG2 and BEL-7402 cells, which may be due to the inhibition of the extracellular regulated protein kinase (ERK) signaling pathway. In addition, these BK receptor inhibitors reversed the cell proliferation induced by BK in HepG2 and BEL-7402 cells by downregulating B1 receptor expression. Inhibiting B1 receptor expression decreased the protein levels of p-ERK and reduced the malignant progression of HCC, providing a potential target for HCC therapy.

Integration model of POSP measurement spatial response function.

The particulate observing scanning polarimeter (POSP) measurement spatial response function (SRF) relates to the weighted contribution of each location within the measurement footprint, which is determined by the percentage of the dwell time of each location on the Earth surface to the overall sampling integration time. The SRF resulting from a combination of the equally weighted instantaneous field of view (IFOV) during integration is required for an accurate modeling. Simply using a mean value SRF assuming an equivalent weight at each sampling position instead of the actual SRF will inevitably introduce errors. Considering the data fusion between POSP and high spatial resolution sensors, a discrete integration method that takes the effect of actual weights into account is proposed in this paper. The simulation results of the integral model and the mean value model show that the larger the intensity change in the sampling area covered by the IFOV of the POSP during a single sampling, the more significant the difference between the two results. Meanwhile, the integration SRF is validated by resampling the simultaneous imaging polarization camera (SIPC) data, which is compared with POSP data acquired at the same time in an aerial experiment. The results show that the integration SRF model is more accurate to characterize the details of POSP measurement than the mean value SRF model. The proposed SRF reduces the root mean square error (RMSE) of convolved results and measurements by 5∼30% with different radiance contrast scene.