Rationalization design, soluble expression and PEG modification of highly active recombinant human-porcine uricase mutant protein.

Uric acid is the end product of purine metabolism in humans due to inactivation of the uricase determined by the mutated uricase gene. Uricase catalyzes the conversion of uric acid into water-soluble allantoin that is easily excreted by the kidneys. Hyperuricemia occurs when the serum concentration of uric acid exceeds its solubility (7 mg/dL). However, modifications to improve the uricase activity is under development for treating the hyperuricemia. Here we designed 7 types of human-porcine chimeric uricase by multiple sequence comparisons and targeted mutagenesis. An optimal human-porcine chimeric uricase mutant (uricase-10) with both high activity (6.33 U/mg) and high homology (91.45 %) was determined by enzyme activity measurement. The engineering uricase was further modified with PEGylation to improve the stability of recombinant protein drugs and reduce immunogenicity, uricase-10 could be more suitable for the treatment of gout and hyperuricemia theoretically.

Vertical distribution of arsenic and bacterial communities in calcareous farmland amending by organic fertilizer and iron-oxidizing bacteria: Field experiment on concomitant remediation.

The migration and transformation mechanisms of arsenic (As) in soil environments necessitate an understanding of its influencing processes. Here, we investigate the subsurface biogeochemical transformation of As and iron (Fe) through amended in the top 20 cm with iron oxidizing bacteria (FeOB) and organic fertilizer (OF). Our comprehensive 400-day field study, conducted in a calcareous soil profile sectioned into 20 cm increments, involved analysis by sequential extraction and assessment of microbial properties. The results reveal that the introduction of additional OF increased the release ratio of As/Fe from the non-specific adsorption fraction (136.47 %) at the subsoil depth (40-60 cm), underscoring the importance of sampling at various depths and time points to accurately elucidate the form, instability, and migration of As within the profile. Examination of bacterial interaction networks indicated a disrupted initial niche in the bottom layer, resulting in a novel cooperative symbiosis. While the addition of FeOB did not lead to the dominance of specific bacterial species, it did enhance the relative abundance of As-tolerant Acidobacteria and Gemmatimonadetes in both surface (39.2 % and 38.76 %) and deeper soils (44.29 % and 23.73 %) compared to the control. Consequently, the amendment of FeOB in conjunction with OF facilitated the formation of poorly amorphous Fe (hydr)oxides in the soil, achieved through abiotic and biotic sequestration processes. Throughout the long-term remediation process, the migration coefficient of bioavailable As within the soil profile decreased, indicating that these practices did not exacerbate As mobilization. This study carries significant implications for enhancing biogeochemical cycling in As-contaminated Sierozem soils and exploring potential bioremediation strategies. ENVIRONMENTAL IMPLICATION: The long-term exposure of sewage irrigation has potential adverse effects on the local ecosystem, causing serious environmental problems. Microorganisms play a vital role in the migration and transformation of arsenic in calcareous soil in arid areas, which highlights the necessity of understanding its dynamics. The vertical distribution, microbial community and fate of arsenic in calcareous farmland soil profile in northwest China were studied through field experiments. The results of this work have certain significance for the remediation of arsenic-contaminated soil in arid areas, and provide new insights for the migration, transformation and remediation of arsenic in this kind of soil.

Borneol serves as an adjuvant agent to promote the cellular uptake of curcumin for enhancing its photodynamic fungicidal efficacy against Candida albicans.

Candida albicans (C. albicans), a major opportunistic pathogenic fungus, is known to cause superficial skin infections. Unfortunately, the misuse of antibiotics has led to the emergence of drug resistance in fungi. Antimicrobial photodynamic therapy (aPDT), a non-antibiotic alternative, has shown potential in treating drug-resistant fungal infections. Curcumin is a photodynamically active phytochemical whose photodynamic fungicidal efficacy is largely dependent on its intracellular accumulation. However, curcumin faces challenges in penetrating the cytoplasm due to its poor water solubility and the fungal cell wall. Borneol, another monoterpenoid phytochemical, is known for its ability to enhance drug absorption. In this study, we showed that borneol improved the cellular uptake of curcumin, thereby enhancing its photodynamic fungicidal efficacy against C. albicans. This effect was attributed to borneol's ability to increase cell permeability. Transcriptomic analysis further confirmed that borneol disrupted the normal structure and function of the C. albicans cell wall and membrane, resulting in dysregulated mRNA expression of related genes and ultimately increased cell permeability. As a result, the excessive accumulation of curcumin in C. albicans triggered the overproduction of intracellular ROS upon exposure to blue light. These excessive intracellular ROS disrupted various cellular structures, interfered with essential cellular processes, inhibited biofilm formation and reduced virulence. Remarkably, borneol was also found to enhance curcumin uptake by C. albicans within biofilms, further enhancing the anti-biofilm efficacy of curcumin-mediated aPDT (Cur-aPDT). In conclusion, the results of this study strongly support the potential of borneol as an adjuvant agent to Cur-aPDT in treating superficial cutaneous fungal infections.

Catalytic Mechanism and Heterologous Biosynthesis Application of Sesquiterpene Synthases.

Sesquiterpenes comprise a diverse group of natural products with a wide range of applications in cosmetics, food, medicine, agriculture, and biofuels. Heterologous biosynthesis is increasingly employed for sesquiterpene production, aiming to overcome the limitations associated with chemical synthesis and natural extraction. Sesquiterpene synthases (STSs) play a crucial role in the heterologous biosynthesis of sesquiterpene. Under the catalysis of STSs, over 300 skeletons are produced through various cyclization processes (C1-C10 closure, C1-C11 closure, C1-C6 closure, and C1-C7 closure), which are responsible for the diversity of sesquiterpenes. According to the cyclization types, we gave an overview of advances in understanding the mechanism of STSs cyclization from the aspects of protein crystal structures and site-directed mutagenesis. We also summarized the applications of engineering STSs in the heterologous biosynthesis of sesquiterpene. Finally, the bottlenecks and potential research directions related to the STSs cyclization mechanism and application of modified STSs were presented.

Research on Classification of Grassland Degeneration Indicator Objects Based on UAV Hyperspectral Remote Sensing and 3D_RNet-O Model.

Real-time and high-precision land cover classification is the foundation for efficient and quantitative research on grassland degradation using remote sensing techniques. In view of the shortcomings of manual surveying and satellite remote sensing, this study focuses on the identification and classification of grass species indicating grassland degradation. We constructed a UAV-based hyperspectral remote sensing system and collected field data in grassland areas. By applying artificial intelligence technology, we developed a 3D_RNet-O model based on convolutional neural networks, effectively addressing technical challenges in hyperspectral remote sensing identification and classification of grassland degradation indicators, such as low reflectance of vegetation, flat spectral curves, and sparse distribution. The results showed that the model achieved a classification accuracy of 99.05% by optimizing hyperparameter combinations based on improving residual block structures. The establishment of the UAV-based hyperspectral remote sensing system and the proposed 3D_RNet-O classification model provide possibilities for further research on low-altitude hyperspectral remote sensing in grassland ecology.

Arsenic and cadmium simultaneous immobilization in arid calcareous soil amended with iron-oxidizing bacteria and organic fertilizer.

Immobilization stands as the most widely adopted remediation technology for addressing heavy metal(loid) contamination in soil. However, it is crucial to acknowledge that this process does not eliminate pollutants; instead, it confines them, potentially leaving room for future mobilization. Presently, our comprehension of the temporal variations in the efficacy of immobilization, particularly in the context of its applicability to arid farmland, remains severely limited. To address this knowledge gap, our research delves deep into the roles of iron-oxidizing bacteria (FeOB) and organic fertilizer (OF) in the simultaneous immobilization of arsenic (As) and cadmium (Cd) in soils. We conducted laboratory incubation and field experiments to investigate these phenomena. When OF was combined with FeOB, a noteworthy transformation of available As and Cd into stable species, such as the residual state and combinations with Fe-Mn/Al oxides, was observed. This transformation coincided with changes in soil properties, including pH, Eh, soluble Fe, and dissolved organic carbon (DOC). Furthermore, we observed synergistic effects between available As and Cd when treated with bacteria and OF individually. The stabilization efficiency of As and Cd, as determined by the Toxicity Characteristic Leaching Procedure, reached its highest values at 33.39 % and 24.67 %, respectively, after 120 days. Nevertheless, the formation of iron­calcium complexes was disrupted due to pH fluctuations. Hence, long-term monitoring and model development are essential to enhance our understanding of the remediation process. The application of organic fertilizer and the use of FeOB in calcareous soil hold promise for the restoration of polluted soil and the maintenance of soil health by mitigating the instability of heavy metals(loid).

Knowledge graph construction based on granulosa cells transcriptome from polycystic ovary syndrome with normoandrogen and hyperandrogen.

PCOS is a widespread disease that primarily caused in-pregnancy in pregnant-age women. Normoandrogen (NA) and Hyperandrogen (HA) PCOS are distinct subtypes of PCOS, while bio-markers and expression patterns for NA PCOS and HA PCOS have not been disclosed. We performed microarray analysis on granusola cells from NA PCOS, HA PCOS and normal tissue from 12 individuals. Afterwards, microarray data were processed and specific genes for NA PCOS and HA PCOS were identified. Further functional analysis selected IL6R and CD274 as new NA PCOS functional markers, and meanwhile selected CASR as new HA PCOS functional marker. IL6R, CD274 and CASR were afterwards experimentally validated on mRNA and protein level. Subsequent causal relationship analysis based on Apriori Rules Algorithm and co-occurrence methods identified classification markers for NA PCOS and HA PCOS. According to classification markers, downloaded transcriptome datasets were merged with our microarray data. Based on merged data, causal knowledge graph was constructed for NA PCOS or HA PCOS and female infertility on NA PCOS and HA PCOS. Gene-drug interaction analysis was then performed and drugs for HA PCOS and NA PCOS were predicted. Our work was among the first to indicate the NA PCOS and HA PCOS functional and classification markers and using markers to construct knowledge graphs and afterwards predict drugs for NA PCOS and HA PCOS based on transcriptome data. Thus, our study possessed biological and clinical value on further understanding the inner mechanism on the difference between NA PCOS and HA PCOS.

Evaluation of heavy metal speciation distribution in soil and the accumulation characteristics in wild plants: A study on naturally aged abandoned farmland adjacent to tailings.

Heavy metal composite pollution is widespread in the surrounding environment of tailings ponds in arid and semi-arid regions, leading to the abandonment of substantial agricultural land. This study investigates the speciation distribution and plant accumulation characteristics of heavy metals in abandoned farmland with different durations of natural aging. The aim is to comprehend the local heavy metal behavior pattern in the soil-plant system and offer insights for environmental remediation. Our findings reveal that Cd stands out as the primary heavy metal pollutant in this area. The mobility ranking of heavy metals is Cd > Pb > Zn > Cu, with Cd and Pb mobility decreasing along the basin. Notably, active Pb exhibits a higher affinity for soil binding compared to other metals. The predominant plant species in the region are primarily small shrubs, herbaceous plants, and semi-shrubs that demonstrate tolerance to drought and salt. Most plant samples showed elevated levels of Cd, Pb, and Zn, surpassing the maximum tolerance levels for dietary minerals in livestock. This elevated metal content poses potential threats to the health of local livestock and wildlife, yet it is also considered a potential for phytoremediation. Selected dominant plant species from the current study include Kalidium foliatum & gracile which shows potential as a Cd accumulator and indicator. Neotrinia splendens and Reaumuria songarica demonstrate potential as Cd excluders, with the latter exhibiting higher tolerance to Cd (62.9 mg/kg). Additionally, our observations indicate that different plant parts exhibit distinct responses to heavy metals, and Zn synergistically influences the aerial part accumulation of Cd. This study holds significant importance in understanding the complex behavior patterns of multi-metal pollutants in the natural environment. The identification of native plants with remediation potential is valuable for phytoremediation of environment pollution in mining area.

A Comprehensively Prognostic and Immunological Analysis of PARP11 in Pan-cancer.

Poly (ADP ribose) polymerase family member 11(PARP11) has important immune regulatory functions in viral infection and tumor immune response. Particularly, PARP11 showed protumor activities in multiple preclinical murine models. However, no systematic pan-cancer analysis has been conducted to explore PARP11 function. In this study we used multiple databases to assess PARP11 expression, which associations with clinical outcomes, immune checkpoint factors, prognostic significance, genomic characteristics, and immunological aspects. The analysis revealed varying expression levels of PARP11 across different cancer types and a significant correlation between its expression and immune cell infiltration. Insights from the CellMiner database suggest a strong link between PARP11 expression and sensitivity to anticancer drugs, highlighting its potential as a therapeutic target. Moreover, PARP11 expression correlates with patient survival during anti-PD1 and anti-CTLA4 treatments, suggested that PARP11 would be a predictor of immune checkpoint inhibitor (ICI) treatment. In summary, PARP11 would be a potential immunoregulatory target and a diagnosis and prognosis marker for certain types of cancers. The detailed mechanisms of PARP11 in tumor immune responses need to be further investigated.

Association of SOX6 gene polymorphisms with Kashin-Beck disease risk in the Chinese Han population.

Kashin-Beck disease (KBD) is an endemic osteochondropathy. A specific gene called SRY-box transcription factor 6 (SOX6) is important for forming cartilage. This study aims to explore the potential correlation between SOX6 single nucleotide polymorphisms (SNPs) and KBD risk for the first time. In the case-control study, 735 unrelated Chinese Han individuals were enrolled. The four mutation sites of the SOX6 gene (rs4539287 G/A, rs3203295 C/A, rs7928675 C/A, and rs10832681 A/G) were screened and genotyped on the Agena MassARRAY platform. The correlation between SOX6 SNPs and KBD risk was explored based on logistic regression analysis. The interaction between SNP and SNP was analyzed based on the multi-factor dimensionality reduction (MDR) method. Overall analysis revealed a remarkable correlation between rs7928675 and rs10832681 and the reduction of KBD risk (p < 0.05). Subgroup analyses further indicated that these two SNPs have a significant protective effect on KBD risk among participants aged ≤65 years, males, and non-smokers (p < 0.05). MDR displayed a marked interaction between rs3203295 and rs10832681. Our study revealed that SOX6 rs7928675 and rs10832681 are markedly correlated with a reduced risk of KBD in the Chinese Han population, providing a new direction for the prevention, diagnosis, and treatment of KBD.

Combined Filtering Method for Offshore Oil and Gas Platform Point Cloud Data Based on KNN_PCF and Hy_WHF and Its Application in 3D Reconstruction.

With the increasing scale of deep-sea oil exploration and drilling platforms, the assessment, maintenance, and optimization of marine structures have become crucial. Traditional detection and manual measurement methods are inadequate for meeting these demands, but three-dimensional laser scanning technology offers a promising solution. However, the complexity of the marine environment, including waves and wind, often leads to problematic point cloud data characterized by noise points and redundancy. To address this challenge, this paper proposes a method that combines K-Nearest-Neighborhood filtering with a hyperbolic function-based weighted hybrid filtering. The experimental results demonstrate the exceptional performance of the algorithm in processing point cloud data from offshore oil and gas platforms. The method improves noise point filtering efficiency by approximately 11% and decreases the total error by 0.6 percentage points compared to existing technologies. Not only does this method accurately process anomalies in high-density areas-it also removes noise while preserving important details. Furthermore, the research method presented in this paper is particularly suited for processing large point cloud data in complex marine environments. It enhances data accuracy and optimizes the three-dimensional reconstruction of offshore oil and gas platforms, providing reliable dimensional information for land-based prefabrication of these platforms.

MYSM1 acts as a novel co-activator of ERα to confer antiestrogen resistance in breast cancer.

Endocrine resistance is a crucial challenge in estrogen receptor alpha (ERα)-positive breast cancer (BCa). Aberrant alteration in modulation of E2/ERα signaling pathway has emerged as the putative contributor for endocrine resistance in BCa. Herein, we demonstrate that MYSM1 as a deubiquitinase participates in modulating ERα action via histone and non-histone deubiquitination. MYSM1 is involved in maintenance of ERα stability via ERα deubiquitination. MYSM1 regulates relevant histone modifications on cis regulatory elements of ERα-regulated genes, facilitating chromatin decondensation. MYSM1 is highly expressed in clinical BCa samples. MYSM1 depletion attenuates BCa-derived cell growth in xenograft models and increases the sensitivity of antiestrogen agents in BCa cells. A virtual screen shows that the small molecule Imatinib could potentially interact with catalytic MPN domain of MYSM1 to inhibit BCa cell growth via MYSM1-ERα axis. These findings clarify the molecular mechanism of MYSM1 as an epigenetic modifier in regulation of ERα action and provide a potential therapeutic target for endocrine resistance in BCa.

BAP18 acting as a novel peroxisome proliferator-activated receptor α co-regulator contributes to hepatocellular carcinoma progression.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide with a poor prognosis. The therapeutic outcomes of HCC patients are urgently needed to be improved, and predictive biomarkers for the optimal treatment selection remains to be further defined. In the present study, our results showed that BPTF-associated protein of 18 KDa (BAP18) was highly expressed in HCC tissues. In cultured HCC cells, BAP18 regulated a subset of down-stream genes involved in different functions, particularly including peroxisome proliferator-activated receptor (PPAR) pathway and lipid metabolism. Furthermore, BAP18 co-activated PPARα-mediated transactivation and facilitated the recruitment of nucleosome acetyltransferase of H4 (NuA4)/tat interacting protein 60 (TIP60) complex, thereby increasing histone H4 acetylation on stearoyl-CoA desaturase 1 (SCD1) loci. In addition, BAP18 promoted HCC cell proliferation, increased intracellular lipid levels and enhanced cell survival under the metabolic stress conditions, such as glucose limitation or tyrosine kinase inhibitors (TKIs) treatment. Importantly, higher BAP18 expression was positively correlated with the postoperative recurrence and the poor disease-free survival in clinical patients receiving sorafenib treatment. Altogether, we discovered that BAP18 plays an oncogenic role in the survival and proliferation of HCC cells, and BAP18 may serve as a predictive biomarker for adjunct TKIs treatment in patients with HCC, and further facilitate the precise treatment.

Assessment and machine learning prediction of heavy metals fate in mining farmland assisted by Positive Matrix Factorization.

The accurate pollutant prediction by Machine Learning (ML) is significant to efficient environmental monitoring and risk assessment. However, application of ML in soil is under studied. In this study, a Positive Matrix Factorization (PMF) assisted prediction method was developed with Support Vector Machine (SVM) and Random Forest (RF) for heavy metals (HMs) prediction in mining farmland. Principal Component Analysis (PCA) and Redundancy Analysis (RDA) were selected to pretreat data. Experiment results illustrated Cd was the main pollutant with heavy risks in the study area and Pb was easy to migrate. The method effects of HMs total concentration predicting were PMF > Simple > PCA > PCA - PMF, and RF predicted better than SVM. Data pretreatment by RDA prior inspection improved the model results. Characteristic HMs Tessier fractions prediction received good effects with average R value as 0.86. Risk classification prediction performed good in Cd, Cu, Ni and Zn, however, Pb showed weak effect by simple model. The best classifier method for Pb was PMF - RF method with relatively good effect (Area under ROC Curve = 0.896). Overall, our study suggested the combination between PMF and ML can assist the prediction of HMs in soil. Spatial weighted attribute of HMs can be provided by PMF.

Response of trace elements in urban deposition to emissions in a northwestern river valley type city: 2010-2021.

Anthropogenic activities release significant quantities of trace elements into the atmosphere, which can infiltrate ecosystems through both wet and dry deposition, resulting in ecological harm. Although the current study focuses on the emission inventory and deposition of trace elements, their complex interactions remain insufficiently explored. In this study, we employ emission inventories and deposition data for eight TEs (Cr, Mn, Ni, Cu, Zn, As, Cd, Pb) in Lanzhou City to unveil the relationship between these two aspects. Emissions in Lanzhou can be roughly divided into two periods centered around 2017. Preceding 2017, industrial production constituted the primary source of TEs emissions except for As; coal combustion was the primary contributor to Cr, Mn, and As emissions; waste incineration played a significant role in As, Zn, and Cd emissions; biomass combustion influenced Cr and Cd emissions; and transportation sources were the predominant contributors to Pb and Cu emissions. With the establishment of waste-to-energy plants and the implementation of ultra-low emission retrofits, emissions from these sources decreased substantially after 2017. Consequently, emissions from industrial production emerged as the main source of TEs. The deposition concentrations of Cr, Mn, Ni, Cu, and Pb followed a similar trend to the emissions. However, Cd and As exhibited lower emissions and a less pronounced response relationship. Moreover, Zn concentrations fluctuated within a narrow range and showed a weaker response to emissions. The consistent changes in emissions and TEs deposition concentrations signify a shift in deposition pollution in Lanzhou city from Coal-fired pollution to that driven by transportation and industrial activities. Within this transition, the industrial production process offers significant potential for emission reduction. This insight provides a crucial foundation for managing TEs pollution and implementing strategies to prevent ecological risks.

Molecular and Functional Analyses of Characterized Sesquiterpene Synthases in Mushroom-Forming Fungi.

Sesquiterpenes are a type of abundant natural product with widespread applications in several industries. They are biosynthesized by sesquiterpene synthases (STSs). As valuable and abundant biological resources, mushroom-forming fungi are rich in new sesquiterpenes and STSs, which remain largely unexploited. In the present study, we collected information on 172 STSs from mushroom-forming fungi with experimentally characterized products from the literature and sorted them to develop a dataset. Furthermore, we analyzed and discussed the phylogenetic tree, catalytic products, and conserved motifs of STSs. Phylogenetic analysis revealed that the STSs were clustered into four clades. Furthermore, their cyclization reaction mechanism was divided into four corresponding categories. This database was used to predict 12 putative STS genes from the edible fungi Flammulina velutipes. Finally, three FvSTSs were selected to experimentally characterize their functions. FvSTS03 predominantly produced Δ-cadinol and FvSTS08 synthesized ß-barbatene as the main product; these findings were consistent with those of the functional prediction analysis. A product titer of 78.8 mg/L ß-barbatene was achieved in Saccharomyces cerevisiae via metabolic engineering. Our study findings will help screen or design STSs from fungi with specific product profiles as functional elements for applications in synthetic biology.

A Novel Cone Model Filtering Method for Outlier Rejection of Multibeam Bathymetric Point Cloud: Principles and Applications.

The utilization of multibeam sonar systems has significantly facilitated the acquisition of underwater bathymetric data. However, efficiently processing vast amounts of multibeam point cloud data remains a challenge, particularly in terms of rejecting massive outliers. This paper proposes a novel solution by implementing a cone model filtering method for multibeam bathymetric point cloud data filtering. Initially, statistical analysis is employed to remove large-scale outliers from the raw point cloud data in order to enhance its resistance to variance for subsequent processing. Subsequently, virtual grids and voxel down-sampling are introduced to determine the angles and vertices of the model within each grid. Finally, the point cloud data was inverted, and the custom parameters were redefined to facilitate bi-directional data filtering. Experimental results demonstrate that compared to the commonly used filtering method the proposed method in this paper effectively removes outliers while minimizing excessive filtering, with minimal differences in standard deviations from human-computer interactive filtering. Furthermore, it yields a 3.57% improvement in accuracy compared to the Combined Uncertainty and Bathymetry Estimator method. These findings suggest that the newly proposed method is comparatively more effective and stable, exhibiting great potential for mitigating excessive filtering in areas with complex terrain.

Enzyme and Metabolic Engineering Strategies for Biosynthesis of α-Farnesene in Saccharomyces cerevisiae.

α-Farnesene, a type of acyclic sesquiterpene, is an important raw material in agriculture, aircraft fuel, and the chemical industry. In this study, we constructed an efficient α-farnesene-producing yeast cell factory by combining enzyme and metabolic engineering strategies. First, we screened different plants for α-farnesene synthase (AFS) with the best activity and found that AFS from Camellia sinensis (CsAFS) exhibited the most efficient α-farnesene production in Saccharomyces cerevisiae 4741. Second, the metabolic flux of the mevalonate pathway was increased to improve the supply of the precursor farnesyl pyrophosphate. Third, inducing site-directed mutagenesis in CsAFS, the CsAFSW281C variant was obtained, which considerably increased α-farnesene production. Fourth, the N-terminal serine-lysine-isoleucine-lysine (SKIK) tag was introduced to construct the SKIK∼CsAFSW281C variant, which further increased α-farnesene production to 2.8 g/L in shake-flask cultures. Finally, the α-farnesene titer of 28.3 g/L in S. cerevisiae was obtained by fed-batch fermentation in a 5 L bioreactor.

Improved Production of Anti-FGF-2 Nanobody Using Pichia pastoris and Its Effect on Antiproliferation of Keratinocytes and Alleviation of Psoriasis.

Fibroblast growth factor 2 (FGF-2) is not only an angiogenic factor, but also a mitogen for epidermal keratinocytes. FGF-2 has been shown to be positively immunoreactive in the basal layer of psoriatic lesions. In previous work, we used the Escherichia coli (E. coli) expression system to biosynthesize a biologically active anti-FGF-2 nanobody (Nb) screened by phage display technology, but the low yield limited its clinical application. In this study, we aimed to increase the yield of anti-FGF-2 Nb, and evaluate its therapeutic potential for psoriasis by inhibiting FGF-2-mediated mitogenic signaling in psoriatic epidermal keratinocytes. We demonstrated a 16-fold improvement in the yield of anti-FGF-2 Nb produced in the Pichia pastoris (P. pastoris) compared to the  E. coli expression system. In vitro, the FGF-2-induced HaCaT cell model (FHCM) was established to mimic the key feature of keratinocyte overproliferation in psoriasis. Anti-FGF-2 Nb was able to effectively inhibit the proliferation and migration of FHCM. In vivo, anti-FGF-2 Nb attenuated the severity of imiquimod (IMQ)-induced psoriatic lesions in mice, and also improved the inflammatory microenvironment by inhibiting the secretion of inflammatory cytokines (IL-1ß, IL-6, IL-23, and TNF-α), chemokines (CXCL1 and CCL20), and neutrophil infiltration in skin lesions. These were mainly related to the suppression of FGF-2-mediated mitogenic signaling in psoriatic keratinocytes. In conclusion, we have improved the production of anti-FGF-2 Nb and demonstrated the modality of attenuating the abnormal proliferative behavior of psoriatic keratinocytes by inhibiting FGF-2-mediated mitogenic signaling, which offers the possibility of treating psoriasis.

Preparation and Properties of High-Temperature-Resistant, Lightweight, Flexible Polyimide Foams with Different Diamine Structures.

Polyimide foam (PIF) is a rising star in high-end applications such as aerospace thermal insulation and military sound absorption. However, the basic rule on molecular backbone design and uniform pore formation of PIF still need to be explored. In this work, polyester ammonium salt (PEAS) precursor powders are synthesized between alcoholysis ester of 3, 3', 4, 4'-benzophenone tetracarboxylic dianhydride (BTDE) and aromatic diamines with different chain flexibility and conformation symmetry. Then, a standard "stepwise heating" thermo-foaming approach is used to prepare PIF with comprehensive properties. A rational thermo-foaming program is designed based on in situ observation of pore formation during heating. The fabricated PIFs have uniform pore structure, and PIFBTDA-PDA shows the smallest size (147 µm) and narrow distribution. Interestingly, PIFBTDA-PDA also presents a balanced strain recovery rate (SR = 91%) and mechanical robustness (0.051 MPa at 25% strain) and its pore structure maintains regularity after 10 compression-recovery cycles, mainly due to high rigidity of the chains. Furthermore, all the PIFs possess lightweight feature (15-20 kg∙m-3), good heat resistance (Tg at 270-340 °C), thermal stability (T5% at 480-530 °C), thermal insulation properties (λ = 0.046-0.053 W∙m-1K-1 at 20 °C, λ = 0.078-0.089 W∙m-1K-1 at 200 °C), and excellent flame retardancy (LOI > 40%). The reported monomer-mediated pore-structure control strategy can provide guidelines for the preparation of high-performance PIF and its industrial applications.