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Laser manipulation of nuclear decay has extremely promising applications. In this study, cutting-edge Gaussian lasers were combined with the latest data on α decay to thoroughly investigate the factors that impact the penetration probability in laser-assisted α decay of nuclei, while considering the deformation of the nucleus. Our calculations reveal that using state-of-the-art laser fields can marginally alter the half-life of α decay by affecting the penetration probability within a narrow range. Moreover, our findings demonstrate two key points: (1) By deriving an analytical formula for the rate of change of the α decay penetration probability in an ultra-intense laser field, we unveil the negative correlation between the α decay energy and the rate of change of the α decay penetration probability. (2) We attribute the wavelength as the determinant of the effect of the average rate of change of the penetration probability, which we explain by reconstructing the laser pulse width and wavelength. This research offers a rapid method to estimate the rate of change of the α-decay penetration probability and serves as a valuable reference for future experimental investigations of laser-nuclear interactions.

Abstract The kidney reabsorbs large amounts of glucose through Na+-glucose cotransporter 2 (SGLT2). P4-ATPase acts together with the β-subunit TMEM30A to mediate the asymmetric distribution of phosphatidylserine (PS), phosphatidylethanolamine (PE), and other amino phospholipids, promoting plasma membrane and internal vesicle fusion, and facilitating vesicle protein transport. We observed reduced TMEM30A expression in renal tubules of DKD and IgA patients, suggesting a potential role of TMEM30A in renal tubular cells. To investigate the role of TMEM30A in renal tubules, we constructed a TMEM30A knockdown cell model by transfecting mouse kidney tubular epithelium cells (TCMK-1) with TMEM30A shRNA. Knockdown of TMEM30A in TCMK-1 cells attenuated vesicle transporter protein synthesis, resulting in reduced transport and expression of SGLT2, which in turn reduced glucose absorption. These data suggested that TMEM30A plays a crucial role in renal tubules.

Land use in karst areas affects soil properties, impacting carbon sinks. Accurate estimation of carbon sink flux in karst areas through zoning and classification is crucial for understanding global carbon cycling and climate change. The peak cluster depression is the largest continuous karst landform region in southern China, with the depressions primarily covered by farmland and influenced by agricultural activities. This study focused on the Guancun Underground River Basin, a typical peak cluster depression basin, where sampling and analysis were conducted during the agricultural period of 2021–2022. Using hydrochemical analysis and isotopic methods, the results indicated that: (1) The primary hydrochemical type in the Guancun Underground River Basin is HCO3-Ca, with hydrochemical composition mainly controlled by carbonate rock weathering. (2) The primary sources of Cl−, SO42−, and NO3− are agricultural activities, with agriculture contributing 0.68 mmol/L to dissolved inorganic carbon (DIC), accounting for about 13.86%, as confirmed by ion concentration analysis and isotope verification. (3) The size of the depression area is proportional to the contribution of agricultural activities to DIC, while also being influenced by dilution effects. A comparison was made regarding the contribution of other land use types to DIC. The impact of land use on DIC in karst processes should not be overlooked, and zoning and classification assessments of carbon sink flux under different influencing factors contribute to carbon peaking and carbon neutrality goals.

Precise detection and localization are prerequisites for intelligent harvesting, while fruit size and weight estimation are key to intelligent orchard management. In commercial banana orchards, it is necessary to manage the growth and weight of banana bunches so that they can be harvested in time and prepared for transportation according to their different maturity levels. In this study, in order to reduce management costs and labor dependence, and obtain non-destructive weight estimation, we propose a method for localizing and estimating banana bunches using RGB-D images. First, the color image is detected through the YOLO-Banana neural network to obtain two-dimensional information about the banana bunches and stalks. Then, the three-dimensional coordinates of the central point of the banana stalk are calculated according to the depth information, and the banana bunch size is obtained based on the depth information of the central point. Finally, the effective pixel ratio of the banana bunch is presented, and the banana bunch weight estimation model is statistically analyzed. Thus, the weight estimation of the banana bunch is obtained through the bunch size and the effective pixel ratio. The R2 value between the estimated weight and the actual measured value is 0.8947, the RMSE is 1.4102 kg, and the average localization error of the central point of the banana stalk is 22.875 mm. The results show that the proposed method can provide bunch size and weight estimation for the intelligent management of banana orchards, along with localization information for banana-harvesting robots.

AbstractObjective The pathogenesis of renal osteopathy and cardiovascular disease suggests the disordered bone–vessel axis in chronic kidney disease–mineral bone disorder (CKD–MBD). However, the mechanism of the bone–vessel axis in CKD–MBD remains unclear.Methods We established a CKD–MBD rat model to observe the pathophysiological phenotype of the bone–vessel axis and performed RNA sequencing of aortas to identify novel targets of the bone–vessel axis in CKD–MBD.Results The microarchitecture of the femoral trabecular bone deteriorated and alveolar bone loss was aggravated in CKD–MBD rats. The intact parathyroid hormone and alkaline phosphatase levels increased, 1,25-dihydroxyvitamin D3 levels decreased, and intact fibroblast growth factor-23 levels did not increase in CKD–MBD rats at 16 weeks; other bone metabolic parameters in the serum demonstrated dynamic characteristics. With calcium deposition in the abdominal aortas of CKD–MBD rats, RNA sequencing of the aortas revealed a significant decrease in inositol 1,4,5-trisphosphate receptor type 2 (ITPR2) gene levels in CKD–MBD rats. A similar trend was observed in rat aortic smooth muscle cells. As a secretory protein, ITPR2 serum levels decreased at 4 weeks and slightly increased without statistical differences at 16 weeks in CKD–MBD rats. ITPR2 serum levels were significantly increased in patients with vascular calcification, negatively correlated with blood urea nitrogen levels, and positively correlated with serum tartrate-resistant acid phosphatase 5b levels.Conclusion These findings provide preliminary insights into the role of ITPR2 in the bone–vessel axis in CKD–MBD. Thus, ITPR2 may be a potential target of the bone–vessel axis in CKD–MBD.

Chronic kidney disease (CKD) has recently become a serious health and social concern. Vascular calcification, a common complication of CKD, is a risk factor that increases the incidence and mortality of cardiovascular events in patients with CKD. However, there are currently no effective therapeutic targets that can facilitate treatment with fewer side effects for vascular calcification in CKD. To identify potential therapeutic targets, we performed label-free quantification (LFQ) analyses of protein samples from rat aortic vascular smooth muscle cells (RASMCs) after high-phosphorus treatment by nano-UPLC–MS/MS. We determined that ubiquitin-specific protease 47 (USP47) may be associated with CKD vascular calcification by regulating the osteogenic transdifferentiation of the vascular smooth muscle cell (VSMC) phenotype, thus suggesting a novel and potentially effective therapeutic target for CKD vascular calcification. USP47 knockdown significantly reduced the expression of β-transducin repeat-containing protein (BTRC), serine/threonine-protein kinase akt-1 (AKT1), Klotho, fibroblast growth factor (FGF23), and matrix Gla protein (MGP) in RASMCs after high-phosphorus treatment. Consistent with the results of protein–protein interaction (PPI) analyses, USP47 may be involved in regulating osteogenic transdifferentiation markers, such as runt-related transcription factor 2 (RUNX2), Klotho, FGF23, and MGP through the BTRC/AKT1 pathway upon CKD vascular calcification. These data indicate that USP47 may be associated with vascular calcification in CKD by regulating osteogenic differentiation of VSMCs. USP47 may regulate osteogenic transdifferentiation in VSMCs upon CKD vascular calcification through a process involving the BTRC/AKT1 pathway. This study identified a novel potential therapeutic target for the treatment of vascular calcification in CKD.

Vascular calcification is prominent in patients with chronic kidney disease (CKD) and is a strong predictor of cardiovascular mortality in the CKD population. However, the mechanism underlying CKD-associated vascular calcification remains unclear. To identify potential therapeutic targets, a 5/6 nephrectomy rat model was established by feeding of a high-phosphorous diet as the CKD group and compared with sham group rats at 4 and 16 weeks. Sequencing analyses of the rat aorta revealed 643 upregulated and 1023 downregulated genes at 4 weeks, as well as 899 upregulated and 1185 downregulated genes at 16 weeks in the CKD group compared to the sham group. Bioinformatics analyses suggested that SOST (which encodes sclerostin) and Wnt signaling are involved in CKD-associated vascular calcification. Furthermore, protein-protein interactions analysis revealed interactions between SOST, WNT5A, and WNT5B, that involved runt-related transcription factor 2 (RUNX2) and transgelin (TAGLN). SOST was increased in CKD-associated vascular calcification following reduction of the Wnt signaling, including WNT5A and WNT5B, both in vivo and in vitro. TargetScan was used to predict the microRNAs (miRNAs) targeting WNT5A and WNT5B. The expression levels of miR-542-3p, miR-298-3p, miR-376b-5p, and miR-3568 were significantly reduced, whereas that of miR-742-3p was significantly increased in calcified rat aortic vascular smooth muscle cells (VSMCs). In CKD rat aortas, the expression of miR-542-3p, miR-298-3p, miR-376b-5p, miR-3568, miR-742-3p, and miR-22-5p were significantly reduced at both 4 and 16 weeks. Altogether, owing to several assessments, potentially diagnostic and prognostic biomarkers for improving common CKD diagnostic tools were identified in this study. Abbreviations: BUN: blood urea nitrogen; CKD: chronic kidney disease; CKD-MBD: chronic kidney disease-mineral bone disorder; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GO: the Gene Ontology; HE: hematoxylin-eosin; HRP: horseradish peroxidase; KEGG: Kyoto Encyclopedia of Genes and Genomes; MiRNAs: microRNAs; PAS: periodic acid-Schiff; RUNX2: runt-related transcription factor 2; SCr: serum creatinine; STRING: the Search Tool for the Retrieval of Interacting Genes/Proteins; TAGLN: transgelin; VSMC: vascular smooth muscle cell.

Abstract Abnormality of enhancer regulation has emerged as one of the critical features for cancer cells. KDM5C is a histone H3K4 demethylase and frequently mutated in several types of cancer. It is critical for H3K4me3 and activity of enhancers, but its regulatory mechanisms remain elusive. Here, we identify TRIM11 as one ubiquitin E3 ligase for KDM5C. TRIM11 interacts with KDM5C, catalyzes K48-linked ubiquitin chain on KDM5C, and promotes KDM5C degradation through proteasome. TRIM11 deficiency in an animal model represses the growth of breast tumor and stabilizes KDM5C. In breast cancer patient tissues, TRIM11 is highly expressed and KDM5C is lower expressed, and their expression is negatively correlated. Mechanistically, TRIM11 regulates the enhancer activity of genes involved in cell migration and immune response by targeting KDM5C. TRIM11 and KDM5C regulate MCAM expression and cell migration through targeting H3K4me3 on MCAM enhancer. Taken together, our study reveals novel mechanisms for enhancer regulation during breast cancer tumorigenesis and development.

Carbonate weathering is an important part of the global carbon cycle, acts as an atmospheric and soil CO2 sink. Driven by ecosystem factors and affected by global change, carbon sinks in karst areas have the characteristics of surface and underground carbon sinks.This work briefly introduces the relationship between the karst carbon cycle and global change, discusses the related scientific issues and main progress of karst carbon sinks, analyzes the potential of karst sink increases and land use changes, and further proposes a conceptual model of carbonate weathering processes based on the concept of karst critical zones.Carbon sink generated by weathering of carbonate rocks may contribute to the "missing sink" of the global carbon cycle and play a role in mitigating the release of soil CO2 to the atmosphere, thus becoming an important regulator of the item of "land use change" (ELUC) in the global carbon cycle model.The carbonate weathering process responds quickly to short-time scale environmental factors, which is the core driving mechanism that connects biological, hydrological, as well as geochemical processes in karst critical zones.The karst carbon cycle can be regarded as an extension or lateral component of the soil-ecosystem carbon cycle, which together constitute a complete terrestrial shallow surface carbon cycle system in karst areas.The negative feedback effect of carbonate weathering on the increase of atmospheric CO2 concentration and the continuous promotion of rock desertification control and ecological restoration contain huge potential for karst carbon sequestration and sink increase.The monitoring and research on seasonal and regional variations in soil CO2 should be strengthened, and an inverse model based on the correlation between soil CO2 and the watershed hydrochemistry index should be constructed to estimate the background of the regional carbon sink and evaluate the annual carbon sink increment and potential, thus providing a clearer and effective scheme and approach for karst sink increase.

Summary: We aimed to investigate the mechanisms of Brahma related gene 1 (BRG1) in promoting vascular calcification in chronic kidney disease (CKD). The expression of BRG1 was examined in high phosphorus stimulated rat aortic smooth muscle cells (RASMCs) and calcified artery tissues from rat models and hemodialysis patients. Autophagosome formation was measured in high phosphorus stimulated RASMCs with and without BRG1 knock-down. We also detected the coexistence of BGR1 and exosomes, and measured the circulatory levels of BRG1 in the hemodialysis patients. BRG1 promoted the osteogenic transdifferentiation of RASMCs. Silencing BRG1 prevented autophagy from being induced by high phosphorus stimulation in RASMCs. Increased expression of BRG1 was observed in calcified blood vessels. Serum BRG1 level increased in the hemodialysis patients. BRG1 was involved in the development of high phosphorus induced osteogenic phenotype in vitro and in vivo, and its underlying mechanism might be facilitating autophagy.

Revealing the multidimensional value of cultivated land resources, improving calculation methods, and exploring their spatial distribution characteristics and influencing factors are crucial for the enhancement of natural resource accounting systems and the protection of cultivated land resources. This study takes Guangxi, China, as an example and constructs a comprehensive multidimensional value evaluation system for cultivated land resources at the county scale. The income capitalization method, substitution market method, and value equivalent correction method were applied to calculate the economic, social, and ecological values of cultivated land resources in 111 counties in 2020. Furthermore, spatial autocorrelation analysis was employed to study their distribution characteristics and influencing factors. The results show that: (1) In 2020, the total value of cultivated land resources in Guangxi was USD 2859.3 billion, with the economic, social, and ecological values were USD 1674.2 billion, USD 417.7 billion and USD 767.3 billion USD, respectively. (2) The economic and social value of cultivated land per hectare at the county scale in Guangxi demonstrates similar spatial distribution patterns. High-value counties exhibit a strip-like distribution along the eastern edge, following a north–south orientation, while low-value counties form clusters in the central and western regions. (3) There is a significant spatial clustering effect of all values of cultivated land resources in local space, with “high-high” and “low-low” clustering. (4) The level of economic development in counties has a negative impact on the ecological value of cultivated land resources, while it has a positive impact on their social value. (5) Natural conditions, agricultural infrastructure conditions and agricultural development approaches are the key factors affecting the value of cultivated land resources.

It is recognized that karst processes are actively involved in the current global carbon cycle based on twenty years research, and the carbon sink occurred in karst processes is possibly an important part of “missing sink” in global carbon cycle. In this paper, an overview is given on karst carbon cycle research, and influence factors, formed carbon pools (background carbon sink) and sink increase potentials of current karst carbon cycle are analyzed. Carbonate weathering could contribute to the imbalance item (BIM) and land use change item (ELUC) in the global carbon cycle model, owing to its uptake of both atmospheric CO2 (carbon sink effect) and CO2 produced by soil respiration (carbon source reduction effect). Karst carbon sink includes inorganic carbon sink resulted from hydrogeochemical process and organic carbon sink generated by aquatic photosynthetic DIC conversion, forming relatively stable river (reservoir) water body or sediment carbon sink. The sizes of both sinks are controlled by terrestrial ecosystems and aquatic ecosystems, respectively. Desertification rehabilitation and carbon sequestration by aquatic plants are two effective ways to increase the carbon sink in karst area. It is estimated that the rate of carbon sink is at least 381 000 t CO2/a with vegetation restoration and afforestation in southwest China karst area, while the annual organic carbon sink generated by aquatic photosynthesis is about 84 200 t C in the Pearl River Basin. The development of a soil CO2 based model for assessment of regional dissolution intensity will help to improve the estimation accuracy of carbon sink increase and potential, thus provide a more clear and efficient karst sink increase scheme and pathway to achieve the goals of “double carbon”. With the deep investigation on karst carbon cycle, mechanism and carbon sink effect, and the improvement of watershed carbon sink measurement methods and regional sink increase evaluation approaches. Karst carbon sink is expected to be included in the list of atmospheric CO2 sources/sinks of the global carbon budget in the near future.

Septic acute kidney injury (AKI) is commonly associated with renal dysfunction and high mortality in patients. Owing to the rapid and violent occurrence of septic AKI with inflammation, there are no effective therapies to clinically treat it. Embelin, a natural product, has a potential regulatory role in immunocytes. However, the role and mechanism of embelin in septic AKI remains unknown. This study aimed to elucidate the role of embelin in macrophage regulation in lipopolysaccharide (LPS)-induced septic AKI. Embelin was intraperitoneally administered to mice after LPS injection. And bone marrow-derived macrophages (BMDMs) were subsequently isolated from the mice to explore the immunomodulatory role of embelin in macrophages. We found that embelin attenuated renal dysfunction and pathological renal damage in the LPS-induced sepsis mouse model. Molecular docking predicted that embelin could bind to phosphorylated NF-κB p65 at the ser536 site. Embelin inhibited the translocation of NF-κB p65 via phosphorylation at ser536 in LPS-induced AKI. It also reduced the secretion of IL-1β and IL-6 and increased the secretion of IL-10 and Arg-1 of BMDMs and mice after LPS stimulation, indicating that embelin suppressed macrophage M1 activation in LPS-induced AKI. Therefore, embelin attenuated LPS-induced septic AKI by suppressing NF-κB p65 at ser536 in activated macrophages. This study preclinically suggests a therapeutic role of embelin in septic AKI.

Background: The pharmacological activity of dimethyl fumarate (DMF) in treating psoriasis and multiple sclerosis (MS) is not fully understood. DMF is hydrolysed to monomethyl fumarate (MMF) in vivo, which is believed to account for the therapeutic effects of DMF. However, previous studies have provided evidence that DMF also enters the circulation. Given that DMF is short-lived in the blood, whether DMF has a therapeutic impact is still unclear.Methods: Lipopolysaccharide (LPS)-mediated RAW264.7 cell activation was used as a model of inflammation to explore the anti-inflammatory effects of short-term DMF exposure in vitro. Whole blood LPS stimulation assay was applied to compare the anti-inflammatory effects of DMF and MMF in vivo. Griess assay was performed to examined nitrite release. The expression of pro-inflammatory cytokines and transcription factors were measured by quantitative PCR (qPCR), ELISA and Western blot. Depletion of intracellular glutathione (GSH) was evaluated by Ellman’s assay. Luciferase reporter assays were performed to evaluate DMF effects on Nrf2-ARE pathway activation, promoter activity of Nfkbiz and mRNA stability of Nfkbiz. Binding of STAT3 to the IκBζ promoter were examined using Chromatin immunoprecipitation (ChIP) assay.Results: Short-term exposure to DMF significantly inhibited the inflammatory response of RAW264.7 cells and suppressed LPS-induced IκBζ expression. Importantly, oral DMF but not oral MMF administration significantly inhibited IκBζ transcription in murine peripheral blood cells. We demonstrated that the expression of IκBζ is affected by the availability of intracellular GSH and regulated by the transcription factor Nrf2 and STAT3. DMF with strong electrophilicity can rapidly deplete intracellular GSH, activate the Nrf2-ARE pathway, and inhibit the binding of STAT3 to the IκBζ promoter, thereby suppressing IκBζ expression in macrophages.Conclusion: These results demonstrate the rapid anti-inflammatory effects of DMF in macrophages, providing evidence to support the direct anti-inflammatory activity of DMF.

Abstract The selection of native greening plants to improve rural greening technology is crucial for enriching methods of building rural plant landscapes. However, there are few studies from the perspective of visual preference using quantitative methods. By using eye-tracking technology, this study studies students in the Central South University of Forestry and Technology and villagers in Changkou Village, Fujian Province, employing pictures of plant organs—leaves, flowers, and fruits—as stimulating materials to analyze five indicators: the total duration of fixations, the number of fixations, average duration of fixations, average pupil size and average amplitude of saccades. A number of findings came from this research First, people visually prefer leaves, followed by flowers and fruits. In terms of species, Photinia × fraseri, Metasequoia glyptostroboides, Photinia serratifolia, Cunninghamia lanceolata and Koelreuteria bipinnata have higher overall preference. Families such as Malvaceae, Fabaceae, Araliaceae, Myricaceae and Cupressaceae have stronger visual attraction than others. Second, there are distinct differences in the preference of shapes and textures of leaves: aciculiform, strip, cordiform, sector and jacket-shape are more attractive; leather-like leaves have a higher visual preference than paper-like leaves; different colors and whether leaves are cracked or not have little effect on leaf observation. Third, the preference for flowers with different inflorescence and colors is significant. Capitulum, cymes and panicles are more attractive; purple is the most preferred color, followed by white, yellow and red. Finally, there are significant differences in preferences for fruit characteristics, with medium-sized fruits and black fruits preferred, while kidney-shaped and spoon-shaped fruits are considered more attractive. Pomes, pods, samaras, and berries have received relatively more attention.

In order to improve the understanding of the global carbon cycle and the stability of karst carbon sinks, it is necessary to better understand the source, distribution and transformation characteristics of organic matter (OM) in aquatic ecosystems. Here, stable isotope ratios (δ13C and δ15N), elemental analysis (C/N ratios), and lipid biomarkers were analyzed for dissolved organic matter (DOM) (0.7 μm) of water, and organic matter from sediment cores (SCOM) to identify the sources, distribution, and transformation of OM in a subtropical karst reservoir. The results showed that short-chain (C14–20) n-alkyl lipids were more abundant than long-chain (C21–34) n-alkyl lipids in both the DOM and SCOM samples, indicating that bacteria were the primary sources of these lipids, while terrestrial organic matter (OM) made only a minor contribution to the n-alkyl lipid pool, and aquatic plants (macrophytes) OM contributed major contribution to the n-alkyl lipid pool in POM. Microbial activity and lipid degradation were more pronounced in the DOM. Furthermore, terrigenous and macrophyte-derived lipids were found to be more abundant in POM than in DOM and SCOM, suggesting that they are relatively resistant to degradation compared with phytoplankton-derived OM.

Accurate estimate of carbonate weathering and the related carbon sink flux induced by anthropogenic H2SO4 is of great significance for improving understanding of the hydrogeochemical evolution and the global carbon cycle. Here, to quantitatively evaluate the influence of anthropogenic H2SO4 on different lithological carbonate weathering and the related carbon sink budget, karst spring water in the typical limestone and mixed limestone–dolomite catchments in Yaji and Beidiping affected by acid precipitation in southwest China were sampled monthly for the analysis of hydrochemical and δ13CDIC characteristics. Results show for the period of sampling (August 2013 to December 2014) that the average contribution rates of atmospheric inputs and carbonate weathering to total dissolved cations are 2.24% and 97.8%, and 3.09% and 96.9% in Yaji and Beidiping, respectively. The δ13CDIC values (−17.0% to −14.7‰) and the [Ca2+ + Mg2+]/[HCO3−] (0.98 to 1.25) and [Ca2+ + Mg2+]/[HCO3− + SO42−] (approximately 1) equivalent ratios of samples prove that H2CO3 and H2SO4 simultaneously participate in carbonate weathering. The contribution rates of H2SO4 to [Ca2+ + Mg2+] and [HCO3−] produced by carbonate weathering in Yaji and Beidiping are 0–30% and 0–18%, and 0–37% and 0–23%, with average values of 14% and 7%, and 19% and 11%, respectively, suggesting that the influence of H2SO4 on different lithological carbonate weathering is different. H2SO4 precipitation participating in carbonate weathering increases the weathering rate by 14–19%, whereas it decreases the flux of karst carbon sink by 7–11% in Southwest China. Therefore, anthropogenic acids have influenced the global carbon cycle and climate change by carbonate weathering due to the large karst areas in the world, and their influences on different lithological carbonate weathering should not be ignored in the regional and global carbon cycles in future studies.

Abstract Background Neoadjuvant therapy can lead to different tumor regression grades (TRG) in rectal cancer after neoadjuvant therapy. The purposes of this study are to investigate the relationships among TRG, pathologic complete response (pCR) and long-term survival, on the basis of reconstructed individual patient data (IPD). Methods The PubMed, Embase, Ovid and Cochrane CENTRAL databases were searched. The primary endpoint was to evaluate the survival landscape of different TRGs after neoadjuvant therapy and the secondary endpoint was to evaluate the associations between pCR and survival. IPD were reconstructed with Kaplan–Meier curves. Results The 10-year overall survival (OS) and 5-year disease-free survival (DFS) were clearly higher in the pCR group than in the non-pCR (npCR) group (80.5% vs. 48.3, 90.1% vs. 69.8%). Furthermore, the OS and DFS increased with improvement in tumor regression after neoadjuvant therapy. According to the IPD, the pCR group had longer OS (HR = 0.240, 95% CI = 0.177–0.325, p

Numerous compounds present in the ocean are contributing to the development of the biomedical field. Agarose, a polysaccharide derived from marine red algae, plays a vital role in biomedical applications because of its reversible temperature-sensitive gelling behavior, excellent mechanical properties, and high biological activity. Natural agarose hydrogel has a single structural composition that prevents it from adapting to complex biological environments. Therefore, agarose can be developed into different forms through physical, biological, and chemical modifications, enabling it to perform optimally in different environments. Agarose biomaterials are being increasingly used for isolation, purification, drug delivery, and tissue engineering, but most are still far from clinical approval. This review classifies and discusses the preparation, modification, and biomedical applications of agarose, focusing on its applications in isolation and purification, wound dressings, drug delivery, tissue engineering, and 3D printing. In addition, it attempts to address the opportunities and challenges associated with the future development of agarose-based biomaterials in the biomedical field. It should help to rationalize the selection of the most suitable functionalized agarose hydrogels for specific applications in the biomedical industry.

Abstract MLL3 is a histone H3K4 methyltransferase that is frequently mutated in cancer, but the underlying molecular mechanisms remain elusive. Here, we found that MLL3 depletion by CRISPR/sgRNA significantly enhanced cell migration, but did not elevate the proliferation rate of cancer cells. Through RNA-Seq and ChIP-Seq approaches, we identified TNS3 as the potential target gene for MLL3. MLL3 depletion caused downregulation of H3K4me1 and H3K27ac on an enhancer ~ 7 kb ahead of TNS3. 3C assay indicated the identified enhancer interacts with TNS3 promoter and repression of enhancer activity by dCas9-KRAB system impaired TNS3 expression. Exogenous expression of TNS3 in MLL3 deficient cells completely blocked the enhanced cell migration phenotype. Taken together, our study revealed a novel mechanism for MLL3 in suppressing cancer, which may provide novel targets for diagnosis or drug development.

Abstract Background tRNA-derived fragments (tRFs) are 14–40-nucleotide-long, small non-coding RNAs derived from specific tRNA cleavage events with key regulatory functions in many biological processes. Many studies have shown that tRFs are associated with Argonaute (AGO) complexes and inhibit gene expression in the same manner as miRNAs. However, there are currently no tools for accurately predicting tRF target genes. Methods We used tRF-mRNA pairs identified by crosslinking, ligation, and sequencing of hybrids (CLASH) and covalent ligation of endogenous AGO-bound RNAs (CLEAR)-CLIP to assess features that may participate in tRF targeting, including the sequence context of each site and tRF-mRNA interactions. We applied genetic algorithm (GA) to select key features and support vector machine (SVM) to construct tRF prediction models. Results We first identified features that globally influenced tRF targeting. Among these features, the most significant were the minimum free folding energy (MFE), position 8 match, number of bases paired in the tRF-mRNA duplex, and length of the tRF, which were consistent with previous findings. Our constructed model yielded an area under the receiver operating characteristic (ROC) curve (AUC) = 0.980 (0.977–0.983) in the training process and an AUC = 0.847 (0.83–0.861) in the test process. The model was applied to all the sites with perfect Watson–Crick complementarity to the seed in the 3′ untranslated region (3′-UTR) of the human genome. Seven of nine target/nontarget genes of tRFs confirmed by reporter assay were predicted. We also validated the predictions via quantitative real-time PCR (qRT-PCR). Thirteen potential target genes from the top of the predictions were significantly down-regulated at the mRNA levels by overexpression of the tRFs (tRF-3001a, tRF-3003a or tRF-3009a). Conclusions Predictions can be obtained online, tRFTars, freely available at http://trftars.cmuzhenninglab.org:3838/tar/ , which is the first tool to predict targets of tRFs in humans with a user-friendly interface.

Background Characterized by macrophage infiltration, renal inflammation during septic acute kidney injury (AKI) reveals a ubiquitous human health problem. Unfortunately, effective therapies with limited side effects are still lacking. This study is aiming to elucidate the role of Dimethyl fumarate (DMF) in macrophages against oxidative stress of septic AKI. Methods Balb/c mice were gavaged by 50 mg/kg DMF then injected with 10 mg/kg LPS by i.p. We examined LPS-induced renal dysfunction and histological features in murine kidneys. Raw264.7 macrophage cells were also treated with DMF and then induced by LPS. The mitotracker staining was used to follow mitochondria integrity by confocal microscopy. Flow cytometry measured the production of ROS by DCF-HDA and the expression of iNOS. Western blot detected the expression of Nrf-2 and Sirt1. Co-IP measured the interaction between Sirt1 and Nrf-2. Confocal microscopy observed the colocalization of Sirt1 and Nrf-2 in LPS-treated Raw264.7 macrophage cells. Results DMF ameliorated murine LPS nephritis with reduced blood urea nitrogen and serum creatinine, as well as decreased the histological alterations compared to the normal control. DMF significantly inhibited the expression of iNOS and reduced the production of nitrite in Raw264.7 cells following LPS treatment. Our study also revealed the role of DMF in protecting against intracellular ROS accumulation and mitochondria dysfunction in LPS-induced nephritis. DMF facilitated colocalization and interaction between Sirt1 and Nrf-2 in LPS-treated cells. Conclusions This study showed that DMF alleviated LPS-induced nephritis, indicating protective effects of DMF on macrophage against oxidative stress induced by LPS potentially involving Nrf-2-mediated pathway.

Defined differently from apoptosis, necrosis, and autophagy, ferroptosis has been implicated in acute kidney injury (AKI) such as ischemia-reperfusion injury induced AKI, folic acid caused AKI and cisplatin induced AKI. However, whether ferroptosis is involved in LPS induced AKI could be remaining unclear and there is still a lack of therapies associated with ferroptosis in LPS induced AKI without side effects. This study aimed to elucidate the role of isoliquiritigenin (ISL) in ferroptosis of LPS-induced AKI. We used LPS to induce renal tubular injury, followed by treatment with ISL both in vitro and in vivo. Human renal tubular HK2 cells were pretreated with 50 μM or 100 μM ISL for 5 h before stimulation with 2 μg/mL LPS. Mice were administered a single dose of either 50 mg/kg ISL orally or 5 mg/kg ferroptosis inhibitor ferrostatin-1 intraperitoneally before 10 mg/kg LPS injection. We found that LPS could induce mitochondria injury of renal tubular presented as the shape of mitochondria appeared smaller than normal with increased membrane density and are faction or destruction of mitochondrial crista through scanning electron microscope. Ferrostatin-1 significantly protected mice against renal dysfunction and renal tubular damage in LPS-induced AKI. ISL inhibited Fe2+ and lipid peroxidation accumulation in LPS-stimulated HK2 cells. It also increased the expression of GPX4 and xCT, reduced the expression of HMGB1 and NCOA4 then attenuated mitochondria injury in renal tubular following LPS stimulation. These results indicated the potential role of ISL against ferritinophagy-mediated ferroptosis in renal tubular following LPS stimulation.

Plants play a very important role in landscape construction. In order to explore whether different living environment will affect people's preference for the structural features of plant organs, this study examined 26 villagers and 33 college students as the participants, and pictures of leaves, flowers and fruits of plants as the stimulus to conduct eye-tracking and EEG detection experiments. We found that eye movement indicators can explain people's visual preferences, but they are unable to find differences in preferences between groups. EEG indicators can make up for this deficiency, which further reveals the difference in psychological and physiological responses between the two groups when viewing stimuli. The final results show that the villagers and the students liked leaves best, preferring aciculiform and leathery leaves; solitary, purple and capitulum flowers; and medium-sized, spathulate, black and pear fruits. In addition, it was found that the overall attention of the villagers when watching stimuli was far lower than that of the students, but the degree of meditation was higher. With regard to eye movement and EEG, the total duration of fixations is highly positively correlated with the number of fixations, and the average pupil size has a weak negative correlation with attention. On the contrary, the average duration of fixations has a weak positive correlation with meditation. Generally speaking, we believe that Photinia×fraseri, Metasequoia glyptostroboides, Photinia serratifolia, Koelreuteria bipinnata and Cunninghamia lanceolata are superior landscape building plants in rural areas and on campuses; Pinus thunbergii, Myrica rubra, Camellia japonica and other plants with obvious features and bright colours are also the first choice in rural landscapes; and Yulania biondii, Cercis chinensis, Hibiscus mutabilis and other plants with simple structures are the first choice in campus landscapes. This study is of great significance for selecting plants for landscape construction and management according to different environments and local conditions.

FTY720 and IMMH002, prodrugs for sphingosine-1-phosphate receptor 1 (S1P1) agonists, show inadequate and inconsistent levels of phosphorylation in humans compared to that in rats. In this study, FTY720 or IMMH002 analogues (21–24) were designed and synthesized with modified head pieces to improve the biotransformation of the prodrugs to the active phosphorylated forms. Target compounds were synthesized via a convergent route using the key and optically pure building block 9, which was first synthesized via asymmetrically catalyzed amination. The phosphorylation rates of these analogues in rat or human blood were compared. The new methyl-substituted analogue compound 21 showed higher phosphorylation rates in both rats and humans than the parent compound, whereas compound 23 showed improvements in rats, but not in humans. In pharmacokinetics studies of rats, compounds 21 and 23 both had higher levels of phosphorylation than FTY720 and IMMH002. Thus, our study not only yielded new compounds with therapeutic potential, but also showed species differences between rats and humans in response to the structural modifications, which might be useful for predicting the biotransformation behavior and efficacy of this class of prodrugs in the clinic.

ABSTRACT It is critical to identify patients with stage II and III colorectal cancer (CRC) who will benefit from adjuvant chemotherapy (ACT) after curative surgery, while the only use of clinical factors is insufficient to predict this beneficial effect. In this study, we performed genetic algorithm (GA) to select ACT candidate genes, and built a predictive model of support vector machine (SVM) using gene expression profiles from the Gene Expression Omnibus database. The model contained four ACT candidate genes (EDEM1, MVD, SEMA5B, and WWP2) and TNM stage (stage II or III). After using Subpopulation Treatment Effect Pattern Plot to determine the optimal cutoff value of predictive scores, the validated patients from The Cancer Genome Atlas database can be divided into the predictive ACT‐benefit/‐futile groups. Patients in the predictive ACT‐benefit group with 5‐fluorouracil (5‐Fu)–based ACT had significantly longer relapse‐free survival (RFS) compared to those without ACT (P = .015); However, the difference in RFS in the predictive ACT‐futile group was insignificant (P = .596). The multivariable analysis found that the predictive groups were significantly associated with the effect of ACT (Pinteraction = .011). Consequently, we developed a predictive model based on the SVM and GA algorithm which was further validated to define patients who benefit from ACT on recurrence.

Psoriasis is characterized by abnormal proliferation of keratinocytes, as well as infiltration of immune cells into the dermis and epidermis, causing itchy, scaly and erythematous plaques of skin. The understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations currently. Here, we showed that IMMH002, a novel orally active S1P1 modulator, desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and thymus. Using different psoriasis animal models, we demonstrated that IMMH002 could significantly relieve skin damage as revealed by PASI score and pathological injure evaluation. Mechanistically, IMMH002 regulated CD3+ T lymphocytes re-distribution by inducing lymphocytes’ homing, thus decreased T lymphocytes allocation in the peripheral blood and skin but increased in the thymus. Our results suggest that the novel S1P1 agonist, IMMH002, exert extraordinary capacity to rapidly modulate T lymphocytes distribution, representing a promising drug candidate for psoriasis treatment. Keywords: S1P1, S1P1 agonist, IMMH002, Lymphocyte, Psoriasis

Abstract In eukaryote cells, core components of chromatin, such as histones and DNA, are packaged in nucleus. Leakage of nuclear materials into cytosol will induce pathological effects. However, the underlying mechanisms remain elusive. Here, cytoplasmic localization of nuclear materials induced by chromatin dysregulation (CLIC) in mammalian cells is reported. H3K9me3 inhibition by small chemicals, HP1α knockdown, or knockout of H3K9 methylase SETDB1, induces formation of cytoplasmic puncta containing histones H3.1, H4 and cytosolic DNA, which in turn activates inflammatory genes and autophagic degradation. Autophagy deficiency rescues H3 degradation, and enhances the activation of inflammatory genes. MRE11, a subunit of MRN complex, enters cytoplasm after heterochromatin dysregulation. Deficiency of MRE11 or NBS1, but not RAD50, inhibits CLIC puncta in cytosol. MRE11 depletion represses tumor growth enhanced by HP1α deficiency, suggesting a connection between CLIC and tumorigenesis. This study reveals a novel pathway that heterochromatin dysregulation induces translocation of nuclear materials into cytoplasm, which is important for inflammatory diseases and cancer.

κ-carrageenases are members of the glycoside hydrolase family 16 (GH16) that hydrolyze sulfated galactans in red algae, known as κ-carrageenans. In this study, a novel κ-carrageenase gene from the marine bacterium Rhodopirellula sallentina SM41 (RsCgk) was discovered via the genome mining approach. There are currently no reports on κ-carrageenase from the Rhodopirellula genus, and RsCgk shares a low identity (less than 65%) with κ- carrageenase from other genera. The RsCgk was heterologously overexpressed in Escherichia coli BL21 and characterized for its enzymatic properties. RsCgk exhibited maximum activity at pH 7.0 and 40 °C, and 50% of its initial activity was retained after incubating at 30 °C for 2 h. More than 70% of its activity was maintained after incubation at pH 6.0–8.0 and 4 °C for 24 h. As a marine derived enzyme, RsCgk showed excellent salt tolerance, retaining full activity in 1.2 M NaCl, and the addition of NaCl greatly enhanced its thermal stability. Mass spectrometry analysis of the RsCgk hydrolysis products revealed that the enzyme had high degradation specificity and mainly produced κ-carrageenan disaccharide. Comparative molecular dynamics simulations revealed that the conformational changes of tunnel-forming loops under salt environments may cause the deactivation or stabilization of RsCgk. Our results demonstrated that RsCgk could be utilized as a potential tool enzyme for efficient production of κ-carrageenan oligosaccharides under high salt conditions.

Earthen dams with greater fines are more susceptible to failure from the piping. This study employed the coupled computational fluid dynamics (CFD)-discrete element method (DEM) to investigate the impact of the piping erosion process. Results displayed that increasing the fine contents would reduce the particle velocity and drag force for enhancing the erosion resistance. Piping would reduce the stability of the structure at different positions of the sample with various fine contents. The representative volume elements (RVE) were selected to observe the local geometry and material behavior as the erosion progressed. Severe water flows significantly reduced the peak shear strength of the eroded soils for the interactive-underfilled soil, particularly for the downstream side. However, the interactive-overfilled specimen reduced the peak shear strength on the upstream side. Results indicated that the proposed weighted clustering coefficient is a better index to capture the shear strength of the eroded soil matrix, with a high magnitude corresponding to a high peak shear strength. Different local material behavior may lead to differential settlements and associated catastrophic consequences during the piping erosion process, which should draw special attention.

An eco-friendly method for ι-carrageenan extraction from seaweed Eucheuma denticulatum through boiling and using a low concentration of Ca(OH)2 is reported. Compared to the traditional method of ι-carrageenan extraction using NaOH, the reported method using Ca(OH)2 had the advantages of using 93.3% less alkali and 86.8% less water, having a 25.0% shorter total extraction time, a 17.6% higher yield, and a 43.3% higher gel strength of the product. In addition, we evaluated the gel properties and structures of ι-carrageenan products extracted by Ca(OH)2 (Ca-IC) and NaOH (Na-IC). The Fourier transform infrared spectroscopy results showed that the structures of Ca-IC and Na-IC did not change remarkably. The results of the thermogravimetric analysis and differential scanning calorimetry showed that Ca-IC had the same thermal stability as Na-IC. The results of the textural analysis showed that Ca-IC had a higher hardness and better chewiness compared to Na-IC. Rheological results indicated that Ca-IC and Na-IC exhibited shear-thinning and non-Newtonian fluid properties, whereas the viscosity of Ca-IC was less than that of Na-IC. In conclusion, this new method of ι-carrageenan extraction using Ca-IC is markedly better and yields higher quality carrageenan than the conventional method of using Na-IC.

Objective This study compared the impact of gradual oculomotor training (GOT) in blow-out orbital fracture (BOF) reconstruction recovery with the impact of high-intensity trainings. Methods In total, 120 patients with BOF requiring orbital reconstruction surgery were randomly divided into four groups; all groups performed postoperative oculomotor training four times per day. Patients in Groups 1, 2, 3, and 4 performed 10, 20, 30, and 50 sets of all-direction movement per training on the first 3 days, respectively; they performed 10 additional sets per training on the following 4 days. Patients in all groups performed 50 sets per training from 8 days to 3 months postoperatively. Incision healing, pain, and satisfaction rate, as well as degree of diplopia, were recorded during follow-up. Results At 7 days postoperatively, more patients in Group 1 had no/mild swelling and no/mild pain, compared with patients in Group 4. Patients in Groups 1 and 2 had higher satisfaction rates than patients in Group 4. The degree of diplopia did not significantly differ among the groups. Conclusions For patients with BOF, GOT after reconstruction surgery was more beneficial for wound healing, pain relief, and satisfaction; the degree of diplopia did not significantly differ, compared with high-intensity trainings.

As an important enzyme involved in the marine carbon cycle, alginate lyase has received extensive attention because of its excellent degradation ability on brown algae, which is widely utilized for alginate oligosaccharide preparation or bioethanol production. In comparison with endo-type alginate lyases (PL-5, PL-7, and PL-18 families), limited studies have focused on PL-17 family alginate lyases, especially for those with special characteristics. In this study, a novel PL-17 family alginate lyase, Aly23, was identified and cloned from the marine bacterium Pseudoalteromonas carrageenovora ASY5. Aly23 exhibited maximum activity at 35 °C and retained 48.93% of its highest activity at 4 °C, representing an excellent cold-adaptation property. Comparative molecular dynamics analysis was implemented to explore the structural basis for the cold-adaptation property of Aly23. Aly23 had a high substrate preference for poly β-D-mannuronate and exhibited both endolytic and exolytic activities; its hydrolysis reaction mainly produced monosaccharides, disaccharides, and trisaccharides. Furthermore, the enzymatic hydrolyzed oligosaccharides displayed good antioxidant activities to reduce ferric and scavenge radicals, such as hydroxyl, ABTS+, and DPPH. Our work demonstrated that Aly23 is a promising cold-adapted biocatalyst for the preparation of natural antioxidants from brown algae.

Objective This study aimed to determine the effect of parathyroid hormone-related protein (PTHrP) on proliferation of cardiac fibroblasts (CFs) in primary cultures of neonatal Wistar rats. Methods Different PTHrP concentrations were added to CFs of neonatal Wistar rats and the cells were grouped according to the concentrations added. A verapamil (VPL) group and a calcitriol (CAL) group were also established. Changes in cell proliferation and in cyclic adenosine monophosphate and calcium ion levels were identified and recorded. Results We found that as the concentration of PTHrP increased, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT, a tetrazolium salt) colorimetric absorbance values (A values) decreased. These values in the PTHrP groups were significantly lower than those in the control group. MTT colorimetric A values and 3 H-thymidine deoxyribose intake were lower in the VPL group, low-dose CAL group, and the PTHrP 10 −7 mol/L group compared with the control group. However, MTT colorimetric A values and 3 H-thymidine deoxyribose intake were higher in the high-dose CAL group than in the PTHrP 10 −7 mol/L group. As PTHrP concentrations increased, intracellular cyclic adenosine monophosphate concentrations also increased. Conclusion PTHrp, VPL, and low-dose CAL inhibit proliferation of CFs, while high-dose CAL promotes proliferation of CFs.

Background: The prognostic factors for efficacy of poly(ADP-ribose) polymerase (PARP) inhibitors in ovarian cancer remain unknown. The purpose of this study is to evaluate the efficacy of PARP inhibitors and to explore their prognostic factors in ovarian cancer.Methods: PubMed, Embase, and conference databases were searched for relevant prospective clinical trials. The primary outcomes included overall survival (OS), progression-free survival (PFS), and their prognostic factors. Secondary outcomes included PFS2, time to first subsequent therapy (TFST), time to second subsequent therapy (TSST), chemotherapy-free interval (CFI), and their prognostic factors. Hazard ratio (HR) with a 95% confidence interval (CI) was used as an effect measure.Results: PARP inhibitors significantly prolonged PFS in patients with ovarian cancer regardless of their BRCA and HRD status (HR = 0.44, 95% CI = 0.36–0.55). BRCA mutation, HRD-positive status, and sensitivity to platinum represented effective prognostic factors for PFS (Pinteraction < 0.01 and within-trial interaction HR < 1). Other clinicopathological factors did not predict the benefit of PFS (Pinteraction > 0.10). Moreover, PARP inhibitors significantly increased PFS2, TFST, TSST, and CFI, with significant BRCA-related differences. However, HRD-related differences could not be evaluated due to the lack of eligible studies. Furthermore, PARP inhibitors did not translate into prolonged OS, although there was a benefit associated with OS (HR = 0.84, 95% CI = 0.70–1.02). PARP inhibitors used as maintenance therapy after first or subsequent line therapy improved OS (HR = 0.77, 95% CI = 0.63–0.93).Conclusions: PARP inhibitors can significantly prolong PFS, PFS2, TFST, TSST, and CFI in ovarian cancer patients. BRCA mutation, HRD-positive status, and sensitivity to platinum are effective prognostic factors for the efficacy of PARP inhibitors. However, despite the PFS improvement, this does not translate into prolonged OS for patients.

Background: A new ι-carrageenase-producing strain was screened from mangroves and authenticated as Pseudoalteromonas carrageenovora ASY5 in our laboratory. The potential application of this new strain was evaluated. Results: Medium compositions and culturing conditions in shaking flask fermentation were firstly optimized by single-factor experiment. ι-Carrageenase activity increased from 0.34 U/mL to 1.08 U/mL after test optimization. Optimal fermentation conditions were 20°C, pH 7.0, incubation time of 40 h, 15 g/L NaCl, 1.5% (w/v) yeast extract as nitrogen source, and 0.9% (w/v) ι-carrageenan as carbon source. Then, the crude ι-carrageenase was characterized. The optimum temperature and pH of the ι-carrageenase were 40°C and 8.0, respectively. The enzymatic activity at 35–40°C for 45 min retained more than 40% of the maximum activity. Meanwhile, The ι-carrageenase was inhibited by the addition of 1 mmol/L Cd2+ and Fe3+ but increased by the addition of 1 mmol/L Ag+, Ba2+, Ca2+, Co2+, Mn2+, Zn2+, Fe2+, and Al3+. The structure of oligosaccharides derived from ι-carrageenan was detected using electrospray ionization mass spectrometry (ESI-MS). The ι-carrageenase degraded ι-carrageenan, yielding disaccharides and tetrasaccharides as main products. Conclusions: The discovery and study of new ι-carrageenases are beneficial not only for the production of ι-carrageenan oligosaccharides but also for the further utilization in industrial production. Keywords: Disaccharides, Electrospray ionization mass spectrometry (ESI-MS), Enzyme properties, Fermentation optimization, Galactans, Pseudoalteromonas carrageenovora, Sulfated linear polysaccharides, Tetrasaccharides, ι-Carrageenan oligosaccharides, ι-Carrageenan, ι-Carrageenase-producing strain

Optimizing the alkali treatment process alone without tracking the changes of algae and agar quality with each pretreatment process will not achieve the optimal agar yield and final quality. In this study, we monitored the changes of the morphology and weight of algae with each treatment process, and comprehensively analyzed the effects of each pretreatment process on the quality of agar by combining the changes of the physicochemical properties of agar. In conventional alkali-extraction technology, alkali treatment (7%, w/v) alone significantly reduced the weight of algae (52%), but hindered the dissolution of algae, resulting in a lower yield (4%). Acidification could solve the problem of algal hardening after alkali treatment to improve the yield (12%). In enzymatic extraction technology, agar with high purity cannot be obtained by enzyme treatment alone, but low gel strength (405 g/cm2) and high sulfate content (3.4%) can be obtained by subsequent acidification and bleaching. In enzyme-assisted extraction technology, enzyme damage to the surface fiber of algae promoted the penetration of low-concentration alkali (3%, w/v), which ensured a high desulfurization efficiency and a low gel degradation rate, thus improving yield (24.7%) and gel strength (706 g/cm2), which has the potential to replace the traditional alkali-extraction technology.

In this work, the physicochemical properties of maleic anhydride (MAH)-modified κ-carrageenan (κCar) (MC) were characterized and compared with those of native κ-carrageenan (NC). The Fourier transform infrared spectrum of MC exhibited that κCar was successfully modified. Thermogravimetric analysis indicated that the thermal stability of MC was decreased. When the degree of substitution was 0.032, MC exhibited a low gel strength (759 g/cm2), gelling temperature (33.3 °C), and dehydration rate (60.3%). Given the excellent film-forming ability of κCar, MC films were then prepared and were found to have better mechanical and barrier properties (UV and water) than NC films. With regard to optical properties, MC films could completely absorb UV light in the range of 200–236 nm. The water contact angle of MC films was higher than that of NC films. Moreover, the elongation at break increased from 26.9% to 163%. These physicochemical property changes imply that MC can be employed in polysaccharide-based films.

Some commonly used surfactants in cosmetic products raise concerns due to their skin-irritating effects and environmental contamination. Multifunctional, high-performance polymers are good alternatives to overcome these problems. In this study, agarose stearate (AS) with emulsifying, thickening, and gel properties was synthesized. Surfactant-free cosmetic formulations were successfully prepared from AS and carbomer940 (CBM940) mixed systems. The correlation of rheological parameter with skin feeling was determined to study the usability of the mixed systems in cosmetics. Based on rheological analysis, the surfactant-free cosmetic cream (SFC) stabilized by AS-carbomer940 showed shear-thinning behavior and strongly synergistic action. The SFC exhibited a gel-like behavior and had rheological properties similar to commercial cosmetic creams. Scanning electron microscope images proved that the AS-CBM940 network played an important role in SFC’s stability. Oil content could reinforce the elastic characteristics of the AS-CBM940 matrix. The SFCs showed a good appearance and sensation during and after rubbing into skin. The knowledge gained from this study may be useful for designing surfactant-free cosmetic cream with rheological properties that can be tailored for particular commercial cosmetic applications. They may also be useful for producing medicine products with highly viscous or gel-like textures, such as some ointments and wound dressings.

Agarose is a natural seaweed polysaccharide and widely used in the medicine, food, and biological fields because of its high gel strength, non-toxicity, and electrical neutrality. The sulfate group is one of the main charged groups that affect the performance of agarose. In the present study, a simple, eco-friendly, and efficient method was explored for agarose preparation. After desulfation with hydrogen peroxide (H2O2), the sulfate content of agar reached 0.21%. Together with gel strength, electroendosmosis, gelling and melting temperature, the indicators of desulfated agar met the standards of commercially available agarose. Notably, the desulfated agar can be used as an agarose gel electrophoresis medium to separate DNA molecules, and the separation effect is as good as that of commercially available agarose. Further, the H2O2 desulfation process was analyzed. The addition of a hydroxyl radical (HO•) scavenger remarkably decreased the H2O2 desulfation rate, indicating that HO• has a certain role in agar desulfation. Sulfate content detection indicated that sulfur was removed from agar molecules in the form of sulfate ions (SO42−) and metal sulfate. The band absence at 850 cm−1 indicated that the sulfate groups at C-4 of D-galactose in sulfated galactan were eliminated.

Background: Inferior Tieguanyin oolong tea leaves were treated with tannase. The content and bioactivity of catechins in extracts from the treated tea leaves were investigated to assess the improvement in the quality of inferior Tieguanyin oolong tea. Results: Analysis showed that after treatment, the esterified catechin content decreased by 23.5%, whereas non-galloylated catechin and gallic acid contents increased by 15.3% and 182%, respectively. The extracts from tannase-treated tea leaves showed reduced ability to bind to BSA and decreased tea cream levels. The extracts also exhibited increased antioxidant ability to scavenge OH and DPPH radicals, increased ferric reducing power, and decreased inhibitory effects on pancreatic α-amylase and lipase activities. Conclusions: These results suggested that tannase treatment could improve the quality of inferior Tieguanyin oolong tea leaves.

Background: A simple and efficient strategy for agarase immobilization was developed with carboxyl-functionalized magnetic nanoparticles (CMNPs) as support. The CMNPs and immobilized agarase (agarase-CMNPs) were characterized by transmission electron microscopy, dynamic light scattering, vibrating sample magnetometry, scanning electron microscopy, X-ray diffraction, thermogravimetric analysis, and zeta-potential analysis. The hydrolyzed products were separated and detected by ESI-TOF-MS. Results: The agarase-CMNPs exhibited a regular spherical shape with a mean diameter of 12 nm, whereas their average size in the aqueous solution was 43.7 nm as measured by dynamic light scattering. These results indicated that agarase-CMNPs had water swelling properties. Saturation magnetizations were 44 and 29 emu/g for the carriers and agarase-CMNPs, respectively. Thus, the particles had superparamagnetic characteristics, and agarase was successfully immobilized onto the supports. Agaro-oligosaccharides were prepared with agar as substrate using agarase-CMNPs as biocatalyst. The catalytic activity of agarase-CMNPs was unchanged after six reuses. The ESI-TOF mass spectrogram showed that the major products hydrolyzed by agarase-CMNPs after six recycle uses were neoagarotetraose, neoagarohexaose, and neoagarooctaose. Meanwhile, the end-products after 90 min of enzymatic treatment by agarase-CMNPs were neoagarobiose and neoagarotetraose. Conclusions: The enhanced agarase properties upon immobilization suggested that CMNPs can be effective carriers for agarase immobilization. Agarase-CMNPs can be remarkably used in developing systems for repeated batch production of agar-derived oligosaccharides.

A rapid and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for the simultaneous determination of H002 and its phosphorylated metabolite, H002-P and hydroxylated metabolite H002-M, in rat blood. H001, an analogue of H002, was used as the internal standard. Blood samples were prepared by simple protein precipitation. The analytes and internal standard were separated on a Zorbax SB-C18 column with a gradient mobile phase consisting of methanol and water containing 0.1% formic acid at a flow rate of 0.2 mL/min with an operating temperature of 20 °C. The detection was performed on a triple quadrupole tandem mass spectrometer with positive electrospray ionization in multiple-reaction monitoring mode. Linear detection responses were obtained from 0.2–100 ng/mL for H002 and H002-M, while 0.5–100 ng/mL for H002-P. The intra- and inter-day precision (RSD%) was within 11.76%, with the accuracy (RE%) ranging from –9.84% to 9.12%. The analytes were shown to be stable during sample storage, preparation and analytic procedures. The method was applied to determine the pharmacokinetics of H002 in rats, and a preliminary study showed that the pharmacokinetics of H002 correlated with its biological effect on peripheral blood lymphocytes.

Sphingosine-1-phosphate receptor subtype 1 (S1P1) is essential for lymphocyte egress from lymphoid organs into systemic circulation and provides a well-defined drug target for autoimmune disorders. IMMH001, also called SYL930, is a specific S1P1/S1P4/S1P5 modulator. Here, we investigated the potential therapeutic effect of IMMH001 on rheumatoid arthritis (RA). IMMH001 rendered periphery blood lymphocytes insensitive to the egress signal from secondary lymphoid organs. Importantly, in both rat adjuvant-induced arthritis and collagen-induced arthritis models, IMMH001 treatment significantly inhibited the progression of RA and RA-associated histological changes in the joints of Sprague-Dawley rats, including hind paw swelling and arthritic index, and thus reduced the pathological score. Furthermore, IMMH001 markedly decreased proinflammatory cytokine and chemokine release from the damaged joints. These data demonstrated that IMMH001 is a promising drug candidate for RA treatment.

In this work, a non-toxic chitosan-based carrier was constructed via genipin activation and applied for the immobilization of tannase. The immobilization carriers and immobilized tannase were characterized using Fourier transform infrared spectroscopy and thermogravimetric analysis. Activation conditions (genipin concentration, activation temperature, activation pH and activation time) and immobilizations conditions (enzyme amount, immobilization time, immobilization temperature, immobilization pH, and shaking speed) were optimized. The activity and activity recovery rate of the immobilized tannase prepared using optimal activation and immobilization conditions reached 29.2 U/g and 53.6%, respectively. The immobilized tannase exhibited better environmental adaptability and stability. The immobilized tannase retained 20.1% of the initial activity after 12 cycles and retained 81.12% of residual activity after 30 days storage. The catechins composition analysis of tea extract indicated that the concentration of non-ester-type catechins, EGC and EC, were increased by 1758% and 807% after enzymatic treatment. Biological activity studies of tea extract revealed that tea extract treated with the immobilized tannase possessed higher antioxidant activity, higher inhibitory effect on α-amylase, and lower inhibitory effect on α-glucosidase. Our results demonstrate that chitosan activated with genipin could be an effective non-toxic carrier for tannase immobilization and enhancing biological activities of tea extract.

In geotechnical engineering, the seepage phenomena, especially regarding the hydraulic heave, is one of the most dangerous failure mechanisms related to infrastructural stability. Hence, a fundamental understanding of this occurrence is important for the design and construction of water-retaining structures. In this study, a computational fluid dynamics (CFD) solver was developed and coupled with discrete element method (DEM) software to simulate the seepage failure process for the three phases of soil, water, and air. Specimens were constructed with two layers of gap-graded particles to give different permeability properties in the vertical direction. More significant heave failure was observed for the sample with higher permeability in the upper layer. Special attention was drawn to the particle-scale observations of the internal structure and drag force to study the erosion mechanism. The soil filled with air bubbles produced a higher drag force in the region below the retaining wall and showed a larger loss of fine particles than the saturated soil, particularly in the initial stages. The results indicate that the impact of air bubbles would accelerate the development of the heave or boiling phenomenon and influence the stability of the system at an early stage.

Increases in seepage force reduce the effective stress of particles and result in the erosion of particles, producing heave failure and piping. Sheet piles/cutoff walls are often employed in dams to control the seepage. In this study, a computational fluid dynamics solver involving two fluid phases was developed and coupled with discrete element method software to simulate the piping process around a sheet pile/cutoff wall. Binary-sized particles were selected to study the impact of fine particles on the mechanisms of seepage. The seepage phenomenon mainly appeared among fine particles located in the downstream side, with the peak magnitudes of drag force and displacement occurring around the retaining wall. Based on the particle-scale observations, the impact of seepage produced a looser condition for the region concentrated around the retaining wall and resulted in an anisotropic condition in the soil skeleton. The results indicate that heave behavior occurs when the drag force located adjacent to the boundary on the downstream side is larger than the corresponding weight of the bulk soil.

Tannase is widely used in tea beverage processing because of its ability to catalyze the hydrolysis of hydrolysable tannins or gallic acid esters and effectively improve the quality of tea extracts through enzymatic extraction. A new thermophilic tannase was cloned from Aspergillus niger FJ0118 and characterized. The tannase exhibited an optimal reaction temperature of 80 °C and retained 89.6% of the initial activity after incubation at 60 °C for 2 h. The enzymatic extraction of green tea at high temperature (70 °C) for a short time (40 min) was devised on the basis of the superior thermal stability of tannase. The enzymatic reaction significantly increased the total polyphenol content of green tea extract from 137 g·kg−1 to 291 g·kg−1. The enzymatic reaction effectively degraded the ester catechins into non-ester catechins compared with the water extraction method. Results suggested that the thermally stable tannase exhibited potential applications in the enzymatic extraction of green tea beverage.

Nucleolar dominance is related to the expression of 45S rRNA genes inherited from one progenitor due to the silencing of the other progenitor’s rRNA genes. To investigate nucleolar dominance associated with tetraploidization, we analyzed the changes regarding the genetic traits and expression of 45S rRNA genes in tetraploidy hybrid lineage including F1 allotetraploids (4n = 148) and F2 autotetraploids (4n = 200) derived from the distant hybridization of Carassius auratus red var. (2n = 100) () ×Megalobrama amblycephala (2n = 48) (). Results showed that nucleolar dominance from the females was established in F1 hybrids and it was inherited in F2 hybrids, suggesting that tetraploidization can lead to rapid establishment of nucleolar dominance in the hybrid origin’s tetraploid lineage. These results extend the knowledge of nucleolar dominance in polyploidy hybrid animals, which are of significance for the evolution of hybrids in vertebrates.

We have revised the taxonomy of three camaenid and one bradybaenid species from China and described one new subspecies of the genus Bradybaena (Family Bradybaenidae) from Inner Mongolia, China. The genitalia of three Satsuma (Family Camaenidae) species S. mellea stenozona (Moellendorff, 1884), S. meridionalis (Moellendorff, 1884), comb. n. and S. uncopila (Heude, 1882), comb. n. assigned to the genus Bradybaena previously, lack a dart sac and mucous glands. Moreover, the molecular phylogeny has revealed close relationships between the three species and the genus Satsuma. Two species, S. stenozona (Moellendorff, 1884) from Fuzhou and Ganesella citrina Zilch, 1940 from Wuyi Mountain, are considered as synonymous and should be a subspecies of S. mellea mellea (Pfeiffer, 1866) because of the morphological and molecular similarities. Meanwhile, the other two are placed in the genus Satsuma: S. meridionalis (Moellendorff, 1884), comb. n. and S. uncopila (Heude, 1882), comb. n. G. virgo Pilsbry, 1927 differs from species of the genera Ganesella and Satsuma not only in its shell, but also in anatomical characters, such asa dart sac and mucous gland, and lacking a flagellum. Additionally, phylogenetic analyses highly support the sister relationship with other Bradybaena species. Thus, placement of G. virgo Pilsbry, 1927 in the genus Bradybaena is suggested.