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Abstract Background Emerging evidence suggested the association between gut dysbiosis and Alzheimer’s disease (AD) progression. However, it remained unclear how the gut microbiome and neuroinflammation in the brain mutually interact or how these interactions affect brain functioning and cognition. Here we hypothesized that “gut-brain” axis mediated by microbial derived metabolites was expected to novel breakthroughs in the fields of AD research and development. Methods Multiple technologies, such as immunofluorescence, 16s rDNA sequencing, mass spectrometry-based metabolomics (LC-QQQ-MS and GC-MS), were used to reveal potential link between gut microbiota and the metabolism and cognition of the host. Results Microbial depletion induced by the antibiotics mix (ABX) verified that “gut-brain” can transmit information bidirectionally. Short-chain fatty acid-producing (SCFAs-producing) bacteria and amino acid-producing bacteria fluctuated greatly in 5×FAD mice, especially the reduction sharply of the Bifidobacteriaceae and the increase of the Lachnospiraceae family. Concentrations of several Tryptophan-kynurenine intermediates, lactic acid, CD4+ cell, and CD8+ cells were higher in serum of 5×FAD mice, whilst TCA cycle intermediates and Th1/Th2 were lower. In addition, the levels of iso-butyric acid (IBA) in feces, serum, and brain of 5×FAD mice were increased compared with WT-M mice, especially in serum. And IBA in the brain was positively correlated with Aβ and proinflammatory factors. Conclusion Together, our finding highlighted that the alternation in gut microbiota affected the effective communication between the “gut-brain” axis in 5×FAD mice by regulating the immune system, carbohydrate, and energy metabolism.

Abstract Background Gastric cancer is one of the most common malignant tumors worldwide, with high incidence and mortality rates, and it has a complex etiology and complex pathological features. Depending on the tumor type, gastric cancer can be classified as intestinal-type and diffuse-type gastric cancer, each with distinct pathogenic mechanisms and clinical presentations. In recent years, machine learning techniques have been widely applied in the medical field, offering new perspectives for the diagnosis, treatment, and prognosis of gastric cancer patients. Methods This study recruited 2158 gastric cancer patients and constructed prognostic prediction models for both intestinal-type and diffuse-type gastric cancer. Clinical pathological data were collected from patients, and machine learning algorithms were used for feature selection and model construction. The performance of the models was validated with training and testing datasets. The Shapley additive explanations (SHAP) values were used to interpret the model predictions and identify the main factors that influence patient survival. Results In the prognostic model for intestinal-type gastric cancer, the gradient boosting decision tree (GBDT) model demonstrated the best performance, with key features including pTNM, CA125, tumor size, CA199, and PALB. Similarly, in the prognostic model for diffuse-type gastric cancer, the GBDT model was utilized, with key features comprising pTNM, Borrmann type IV disease, lymphocyte (LYM), lactate dehydrogenase (LDH), potassium (K), perineural invasion (PNI), tumor size, and whole stomach location. Risk stratification analysis revealed that the prognosis of high-risk patients was significantly worse than that of low-risk patients. Conclusion Machine learning shows great potential in predicting survival outcomes of gastric cancer patients, providing strong support for the development of personalized treatment plans.

The Daqinghe River Basin is located in the North China Plain. In recent years, however, climate warming, drying, and intense human activities have led to declining ecosystem functions and shrinking wetlands in the region. Understanding streamflow changes in the upstream mountainous areas of the Daqinghe River Basin in this changing environment and identifying the driving factors can provide a scientific basis for water resources management and optimization in these areas. This study focuses on the Beihedian River watershed, the Xidayang Reservoir watershed, and the Wangkuai Reservoir watershed in the upstream mountainous areas of the Daqinghe River. It is based on hydro-meteorological data collected between 1963 and 2019. The methods used in the study include the linear tendency estimation method, the non-parametric Mann-Kendall trend test, the elasticity coefficient method, and hydrological simulation methods. The results of this study suggest that the streamflow, precipitation, and potential evapotranspiration (PET) in the three watersheds showed an overall decreasing trend. The minimum precipitation decrease rate ranged from −1.09 to −0.55 mm/a, and the minimum streamflow decreasing rate at the Beihedian Hydrological Station was −1.32 mm/a, with a minimum range of 0–176.03 mm. Change-point analysis revealed that the streamflow in the Beihedian River and Xidayang Reservoir watersheds experienced a significant change point around 1999, with a significant level of α=0.05. As for the Wangkuai Reservoir watershed, a significant change point was observed around 1980, which is likely attributable to land system reforms and protective forest projects. The attribution analysis which combined both climate change and human activities using the elasticity coefficient method and hydrological simulation methods indicated that climate change contributed an average of 32.93%, 34.50%, and 35.12% to the reduction in streamflow in the three watersheds, respectively. Human activities accounted for an average contribution of 67.07%, 65.50%, and 64.88%, respectively. Water conservancy projects, afforestation, and other human activities were identified as the primary factors contributing to streamflow decreases.

Abstract Purpose To investigate the balance between post-treatment effect and continued nature growth after maxillary protraction treatment in patients with skeletal class III malocclusion. Methods 31 patients aged 8.79 ± 1.65 years with skeletal Class III malocclusion had been treated with maxillary protraction and the treatment lasted an average of 1.16 years. The average observation duration after treatment in the maxillary protraction group was 2.05 ± 0.39 years. In the control groups, a sample of 22 patients (9.64 ± 2.53 years) with untreated skeletal class III malocclusion and 24 patients (9.28 ± 0.96 years) with skeletal class I malocclusion were matched to the treatment group according to age, sex and observation period. The mean observation interval of the control groups was 2.39 ± 1.29 years in the class III group and 1.97 ± 0.49 years in the class I group. Results The active orthopedic treatment effect showed a opposite trend to the natural craniomaxillofacial growth effect after treatment in many aspects. In the observation duration of treatment group, decrease in ANB, Wits appraisal and BAr-AAr were statistically significant compared to class I control group (p 0.05), and overjet decreased significantly relative to both of the two control groups (P

The Multidrug and Toxic Compound Extrusion (MATE) proteins serve as pivotal transporters responsible for the extrusion of metabolites, thereby playing a significant role in both plant development and the detoxification of toxins. The MATE gene family within the Brachypodium distachyon, which is an important model organism of the Poaceae family, remains largely unexplored. Here, a comprehensive identification and analysis of MATE genes that complement B. distachyon were conducted. The BdMATE genes were systematically categorized into five distinct groups, predicated on an assessment of their phylogenetic affinities and protein structure. Furthermore, our investigation revealed that dispersed duplication has significantly contributed to the expansion of the BdMATE genes, with tandem and segmental duplications showing important roles, suggesting that the MATE genes in Poaceae species have embarked on divergent evolutionary trajectories. Examination of ω values demonstrated that BdMATE genes underwent purifying selection throughout the evolutionary process. Furthermore, collinearity analysis has confirmed a high conservation of MATE genes between B. distachyon and rice. The cis-regulatory elements analysis within BdMATEs promoters, coupled with expression patterns, suggests that BdMATEs play important roles during plant development and in response to phytohormones. Collectively, the findings presented establish a foundational basis for the subsequent detailed characterization of the MATE gene family members in B. distachyon.

Heterosis of growth traits in economic fish has benefited the production of aquaculture for many years, yet its genetic and molecular basis has remained obscure. Nowadays, a new germplasm of hybrid Jinhu grouper (Epinephelus fuscoguttatus ♀ × E. tukula ♂), abbreviated as EFT, exhibiting paternal-biased growth heterosis, has provided an excellent model for investigating the potential regulatory mechanisms of heterosis. We integrated transcriptome and methylome to unravel the changes of gene expression, epigenetic modification, and subgenome dominance in EFT compared with maternal E. fuscoguttatus. Integration analyses showed that the heterotic hybrids showed lower genomic DNA methylation levels than the purebred parent, and the up-regulated genes were mostly DNA hypomethylation. Furthermore, allele-specific expression (ASE) detected paternal subgenome dominance-regulated paternal-biased heterosis, and paternal bias differentially expressed genes (DEGs) were wholly up-regulated in the muscle. Multi-omics results highlighted the role of lipid metabolism, particularly “Fatty acid synthesis”, “EPA biosynthesis”, and “Signaling lipids”, in EFT heterosis formation. Coherently, our studies have proved that the eicosapentaenoic acid (EPA) of EFT was greater than that of maternal E. fuscoguttatus (8.46% vs. 7.46%). Finally, we constructed a potential regulatory network for control of the heterosis formation in EFT. Among them, fasn, pparg, dgat1, igf1, pomca, fgf8a, and fgfr4 were identified as key genes. Our results provide new and valuable clues for understanding paternal-biased growth heterosis in EFT, taking a significant step towards the molecular basis of heterosis.

BackgroundNon-suicidal self-injury (NSSI) has become a significant public health issue, especially prevalent among adolescents. The complexity and multifactorial nature of NSSI necessitate a comprehensive understanding of its underlying causal factors. This research leverages the causal discovery methodology to explore these causal associations in children.MethodsAn observational dataset was scrutinized using the causal discovery method, particularly employing the constraint-based approach. By integrating machine learning and causal inference techniques, the study aimed to determine direct causal relationships associated with NSSI. The robustness of the causal relationships was evaluated using three methods to construct and validate it: the PC (Peter and Clark) method, Fast Causal Inference (FCI) method, and the GAE (Graphical Autoencoder) method.ResultsAnalysis identified nine nodes with direct causal relationships to NSSI, including life satisfaction, depression, family dysfunction, sugary beverage consumption, PYD (positive youth development), internet addiction, COVID-19 related PTSD, academic anxiety, and sleep duration. Four principal causal pathways were identified, highlighting the roles of lockdown-induced lifestyle changes, screen time, positive adolescent development, and family dynamics in influencing NSSI risk.ConclusionsAn in-depth analysis of the factors leading to Non-Suicidal Self-Injury (NSSI), highlighting the intricate connections among individual, family, and pandemic-related influences. The results, derived from computational causal analysis, underscore the critical need for targeted interventions that tackle these diverse causative factors.

To study the influence of parameter uncertainty in small pressurized water reactor (SPWR) once-through steam generator (OTSG), the nonlinear mathematical model of the SPWR is firstly established. Including the reactor core model, the OTSG model and the pressurizer model. Secondly, a control strategy that both the reactor core coolant average temperature and the secondary-side outlet pressure of the OTSG are constant is adopted. Then, the uncertainty quantification method is established based on Latin hypercube sampling and statistical method. On this basis, the quantitative platform for parameter uncertainty of the OTSG is developed. Finally, taking the uncertainty in primary-side flowrate of the OTSG as an example, the platform application work is carried out under the variable load in SPWR and step disturbance of secondary-side flowrate of the OTSG. The results show that the maximum uncertainty in the critical output parameters is acceptable for SPWR.

NASH is a highly prevalent metabolic syndrome that has no specific approved agents up to now. BBBP, which mainly contains bile acids, possess various pharmacological properties and some bile acids are available for NASH treatment. Herein, the therapeutic effects and underlying mechanisms of BBBP against NASH were systemically evaluated. In this study, mice received an HFHS diet over a 20-week period to induce NASH with or without BBBP intervention were used to evaluate the effect and underlying mechanisms of BBBP against NASH. Our results demonstrated that BBBP attenuated hepatic steatosis, reduced body weight gain and lipid concentrations, and improved sensitivity to insulin and tolerance to glucose in mice fed an HFHS diet. Metabolomics and transcriptomic analysis revealed that BBBP suppressed the arginine biosynthesis by up-regulating NOS3 expression and the PI3K-Akt signaling pathway was also regulated by BBBP, as indicated by 55 DEGs. Bioinformatic analysis predicted the regulatory effect of the FXR/PXR-PI3K-AKT-NOS3 axis on arginine biosynthesis-related metabolites. These results were further confirmed by the significantly increased mRNA and protein levels of NOS3, PI3K (Pik3r2), and AKT1. And the increased levels of arginine biosynthesis related-metabolites, such as urea, aspartic acid, glutamic acid, citrulline, arginine, and ornithine, were confirmed accurately based on targeted metabolomics analysis. Together, our study uncoded the complicated mechanisms of anti-NASH activities of BBBP, and provided critical evidence inspiring the discovery of innovative therapies based on BBBP in the treatment of NASH.

A land fallow system (LFS) designed to adjust the winter-wheat  summer-maize cropping system to fallow  summer-maize was introduced in Hebei Province to alleviate groundwater depletion in the region. However, some of the water saved was lost through evaporation from bare soil and transpiration by weeds. So far, no measurement has been done in the region to address this non-productive water loss, thereby limiting the water-saving potential of the introduced LFS. Furthermore, the reduction in crop production under the summer-maize – fallow system threatens food security. The objective of this study was to determine which practice is effective to keep soil water during fallow and the exact water-saving potential of different cropping system in the region. Firstly, field experiments were conducted under various soil surface management systems — including plastic mulching (PM), straw mulching (SM), shallow tillage (ST) and weed control (WC). The effects of saving water, controlling weeds and managing nutrients were analyzed under the various surface soil management methods. The results showed that compared with the control (no soil surface management, CK), 177, 64.7, 71.0 and 25.0 mm of water was saved respectively under PM, SM, WC and ST surface soil management methods in 2019–2020. The effect of weed control decreased in the order of PM > WC > SM > ST. While PM significantly increased soil nutrient in all the treatments, the others showed slight but insignificant increases. Secondly, the precise water-use of each of the cropping systems was determined using large lysimeters. The analysis showed that compared with the wheat-maize system, 60–100 mm of water was saved under alternating wheat-soybean, wheat-millet, mung bean – fresh edible maize, spring sweet potato cropping systems. The results were key for technical guide in developing future cultivation adjustment policies.

Tricin, a natural nontoxic flavonoid distributed in grasses and euphorbia plants, has been reported to scavenge free radicals, possess anti-inflammatory and antioxidative effects. However, its autophagic effect on Parkinson's disease (PD) has not been elucidated. By adopting cellular and C. elegans models of PD, the autophagic effect of tricin was identified based on the level of autophagy markers (LC3-II and p62). Besides, the pharmacological effects on neurotransmitters (dopamine), inflammatory cytokines (IFN γ, TNFα, MCP-1, IL-10, IL-6 and IL-17A), histology (hematoxylin & eosin and Nissl staining) and behavioural pathology (open-field test, hindlimb clasping, Y-maze, Morris water-maze and nest building test) were also confirmed in the A53T-α-synuclein transgenic PD mouse model. Further experiments demonstrated that tricin induced autophagic flux and lowered the level of α-synuclein through AMPK-p70s6K- and ATG7-dependent mechanism. Compared to the existing clinical PD drugs, tricin mitigated pathogenesis and symptoms of PD with no observable side effects. In summary, tricin is proposed as a potential adjuvant remedy or nutraceutical for the prevention and treatment of PD.

Abstract Background Dual inhibition of PD-1/PD-L1 and TGF-β pathways is a rational therapeutic strategy for malignancies. SHR-1701 is a new bifunctional fusion protein composed of a monoclonal antibody against PD-L1 fused with the extracellular domain of TGF-β receptor II. This first-in-human trial aimed to assess SHR-1701 in pretreated advanced solid tumors and find the population who could benefit from SHR-1701. Methods This was a dose-escalation, dose-expansion, and clinical-expansion phase 1 study. Dose escalation was initiated by accelerated titration (1 mg/kg q3w; intravenous infusion) and then switched to a 3+3 scheme (3, 10, 20, and 30 mg/kg q3w and 30 mg/kg q2w), followed by dose expansion at 10, 20, and 30 mg/kg q3w and 30 mg/kg q2w. The primary endpoints of the dose-escalation and dose-expansion parts were the maximum tolerated dose and recommended phase 2 dose. In the clinical-expansion part, selected tumors were enrolled to receive SHR-1701 at the recommended dose, with a primary endpoint of confirmed objective response rate (ORR). Results In total, 171 patients were enrolled (dose-escalation: n=17; dose-expansion, n=33; clinical-expansion, n=121). In the dose-escalation part, no dose-limiting toxicity was observed, and the maximum tolerated dose was not reached. SHR-1701 showed a linear dose-exposure relationship and the highest ORR at 30 mg/kg every 3 weeks, without obviously aggravated toxicities across doses in the dose-escalation and dose-expansion parts. Combined, 30 mg/kg every 3 weeks was determined as the recommended phase 2 dose. In the clinical-expansion part, SHR-1701 showed the most favorable efficacy in the gastric cancer cohort, with an ORR of 20.0% (7/35; 95% CI, 8.4–36.9) and a 12-month overall survival rate of 54.5% (95% CI, 29.5–73.9). Grade ≥3 treatment-related adverse events occurred in 37 of 171 patients (22%), mainly including increased gamma-glutamyltransferase (4%), increased aspartate aminotransferase (3%), anemia (3%), hyponatremia (3%), and rash (2%). Generally, patients with PD-L1 CPS ≥1 or pSMAD2 histochemical score ≥235 had numerically higher ORR. Conclusions SHR-1701 showed an acceptable safety profile and encouraging antitumor activity in pretreated advanced solid tumors, especially in gastric cancer, establishing the foundation for further exploration. Trial registration ClinicalTrials.gov , NCT03710265

IntroductionThe mechanism of the immediate adverse drug reactions (ADRs) induced by ShenMai injection (SMI) has not been completely elucidated. Within 30 minutes, the ears and lungs of mice injected with SMI for the first time showed edema and exudation reactions. These reactions were different from the IV hypersensitivity. The theory of pharmacological interaction with immune receptor (p-i) offered a new insight into the mechanisms of immediate ADRs induced by SMI.MethodsIn this study, we determined that the ADRs were mediated by thymus-derived T cells through the different reactions of BALB/c mice (thymus-derived T cell normal) and BALB/c nude mice (thymus-derived T cell deficient) after injecting SMI. The flow cytometric analysis, cytokine bead array (CBA) assay and untargeted metabolomics were used to explain the mechanisms of the immediate ADRs. Moreover, the activation of the RhoA/ROCK signaling pathway was detected by western blot analysis.ResultsIn BALB/c mice, the vascular leakage and histopathology results showed the occurrence of the immediate ADRs induced by SMI. The flow cytometric analysis revealed that CD4+ T cell subsets (Th1/Th2, Th17/Treg) were imbalanced. And the levels of cytokines such as IL-2, IL-4, IL12P70 and INF-γ increased significantly. However, in BALB/c nude mice, all the indicators mentioned above have not changed significantly. The metabolic profile of both BALB/c mice and BALB/c nude mice was significantly changed after injecting SMI, and the notable increase in lysolecithin level might have a greater association with the immediate ADRs induced by SMI. The Spearman correlation analysis revealed that LysoPC (18:3(6Z,9Z,12Z)/0:0) showed a significant positive correlation with cytokines. After injecting SMI, the levels of RhoA/ROCK signaling pathway-related protein increased significantly in BALB/c mice. Protein-protein interaction (PPI) showed that the increased lysolecithin levels might be related to the activation of the RhoA/ROCK signaling pathway.DiscussionTogether, the results of our study revealed that the immediate ADRs induced by SMI were mediated by thymus-derived T cells, and elucidated the mechanisms of such ADRs. This study provided new insights into the underlying mechanism of immediate ADRs induced by SMI.

Different studies on the effects of high-fat diet (HFD) on Alzheimer’s disease (AD) pathology have reported conflicting findings. Our previous studies showed HFD could moderate neuroinflammation and had no significant effect on amyloid-β levels or contextual memory on AD mice. To gain more insights into the involvement of HFD, we performed the whole-transcriptome sequencing and ribosome footprints profiling. Combined with competitive endogenous RNA analysis, the transcriptional regulation mechanism of HFD on AD mice was systematically revealed from RNA level. Mmu-miR-450b-3p and mmu-miR-6540-3p might be involved in regulating the expression of Th and Ddc expression. MiR-551b-5p regulated the expression of a variety of genes including Slc18a2 and Igfbp3. The upregulation of Pcsk9 expression in HFD intervention on AD mice might be closely related to the increase of cholesterol in brain tissues, while Huanglian Jiedu Decoction significantly downregulated the expression of Pcsk9. Our data showed the close connection between the alterations of transcriptome and translatome under the effect of HFD, which emphasized the roles of translational and transcriptional regulation were relatively independent. The profiled molecular responses in current study might be valuable resources for advanced understanding of the mechanisms underlying the effect of HFD on AD.

The global industrialization accelerates the use of fossil fuels and hence the excessive emissions of greenhouse gasses, especially carbon dioxide (CO2), which poses a serious threat to the ecological environment. CO2 capture is considered as a potential strategy to reduce the amount of CO2 released into the atmosphere. The development of adsorption materials that are both economically feasible and effective is the most critical issue. Biochar is a promising candidate for CO2 capture among the capture materials. It offers a diverse range of raw materials and a lower environmental impact than other adsorbent materials. Even though pristine biochar could be employed directly to CO2 capture, it generally exhibits a poor adsorption performance. Therefore, biochar needs to be modified in practical applications to improve physicochemical properties such as specific surface area, pore structure, and surface functional groups. This paper summaries recent research advances in biochar-based adsorbents for CO2 adsorption. Pre-combustion capture technology and post-combustion capture technology are investigated. The production of biochar and the influence of raw materials and process conditions on the adsorption capacity of CO2 are described in detail. The mechanism of CO2 adsorption on biochar is also discussed, which summarized physical and chemical adsorption, respectively, as well as the corresponding presentation of some current methods of physical/chemical modification of biochar. Finally, the future prospects are proposed in order to provide a guideline for the adsorption of CO2 by biochar. Despite the progress made in the production of biochar for CO2 adsorption, more efforts are needed to produce biochar with higher adsorption capacity and long-term stability for large-scale CO2 capture.

Introduction: In a multicenter, open-label, parallel-group, randomized, phase 2 study for pretreated advanced hepatocellular carcinoma (HCC), camrelizumab showed potent antitumor activity and acceptable safety profile. The aim of this report was to provide long-term data and evaluate potential benefit of treatment with camrelizumab beyond progression. Methods: From November 15, 2016, to November 16, 2017, 217 patients received camrelizumab 3 mg/kg intravenously every 2 or 3 weeks. Treatment beyond first Response Evaluation Criteria in Solid Tumors (RECIST)-defined progression (TBP) with camrelizumab was allowed. Results: At data cutoff of December 16, 2019 (>2 years after the last patient enrollment; median duration of follow-up, 13.2 months [IQR 5.7–25.8]), 14 (43.8%) of the 32 responses per blinded independent central review were ongoing. The median duration of response was not reached (range 2.5–30.5 + months). The ongoing response rates at 12, 18, and 24 months were 68.3% (95% confidence interval [CI] 47.7–82.2), 59.8% (95% CI 38.8–75.6), and 53.1% (95% CI 31.0–71.0), respectively. The median overall survival (OS) was 14.2 months (95% CI 11.5–16.3). The 18- and 24-month OS rates were 41.3% (95% CI 34.6–47.9) and 33.7% (95% CI 27.3–40.2), respectively. Of the 172 patients who experienced RECIST-defined progression per investigator, 102 received TBP, while 70 did not (non-TBP). The median OS was 16.9 months (95% CI 13.3–22.6) in the TBP group versus 9.4 months (95% CI 5.8–14.8) in the non-TBP group, and the 18- and 24-month OS rates were 47.5% (95% CI 37.3–56.9) versus 33.1% (95% CI 22.3–44.3) and 38.8% (95% CI 29.2–48.4) versus 23.2% (95% CI 13.8–34.1), respectively. No new safety signals of camrelizumab were observed. Conclusions: With prolonged follow-up, camrelizumab continues to demonstrate the durable response and long survival in pretreated advanced HCC patients with manageable toxicities, especially in those who continued the treatment beyond first RECIST-defined progression.

Background: Although unplanned hospital readmission is an important indicator for monitoring the perioperative quality of hospital care, few published studies of hospital readmission have focused on surgical patient populations, especially in the elderly. We aimed to investigate if machine learning approaches can be used to predict postoperative unplanned 30-day hospital readmission in old surgical patients.Methods: We extracted demographic, comorbidity, laboratory, surgical, and medication data of elderly patients older than 65 who underwent surgeries under general anesthesia in West China Hospital, Sichuan University from July 2019 to February 2021. Different machine learning approaches were performed to evaluate whether unplanned 30-day hospital readmission can be predicted. Model performance was assessed using the following metrics: AUC, accuracy, precision, recall, and F1 score. Calibration of predictions was performed using Brier Score. A feature ablation analysis was performed, and the change in AUC with the removal of each feature was then assessed to determine feature importance.Results: A total of 10,535 unique surgeries and 10,358 unique surgical elderly patients were included. The overall 30-day unplanned readmission rate was 3.36%. The AUCs of the six machine learning algorithms predicting postoperative 30-day unplanned readmission ranged from 0.6865 to 0.8654. The RF + XGBoost algorithm overall performed the best with an AUC of 0.8654 (95% CI, 0.8484–0.8824), accuracy of 0.9868 (95% CI, 0.9834–0.9902), precision of 0.3960 (95% CI, 0.3854–0.4066), recall of 0.3184 (95% CI, 0.259–0.3778), and F1 score of 0.4909 (95% CI, 0.3907–0.5911). The Brier scores of the six machine learning algorithms predicting postoperative 30-day unplanned readmission ranged from 0.3721 to 0.0464, with RF + XGBoost showing the best calibration capability. The most five important features of RF + XGBoost were operation duration, white blood cell count, BMI, total bilirubin concentration, and blood glucose concentration.Conclusion: Machine learning algorithms can accurately predict postoperative unplanned 30-day readmission in elderly surgical patients.

Abstract Background Association of immune-related adverse events with tumor response has been reported. Reactive cutaneous capillary endothelial proliferation (RCCEP) is the most common adverse event related to camrelizumab, an immune checkpoint inhibitor, but lack of comprehensive analyses. In this study, we conducted comprehensive analyses on RCCEP in advanced hepatocellular carcinoma (HCC) patients treated with camrelizumab monotherapy. Methods Data were derived from a Chinese nationwide, multicenter phase 2 trial of camrelizumab in pre-treated advanced HCC. The occurrence, clinicopathological characteristics, and prognostic value of RCCEP were analyzed. Results With a median follow-up of 12.5 months, 145 of the 217 camrelizumab-treated patients (66.8%) experienced RCCEP (all grade 1 or 2). RCCEP occurred on the skin surface, mainly on the skin surface of head, face, and trunk. RCCEP could be divided into 5 types including “red-nevus-like,” “pearl-like,” “mulberry-like,” “patch-like,” and “tumor-like,” according to the morphological features. RCCEP biopsy and pathology showed capillary endothelial hyperplasia and capillary hyperplasia in dermis. Significant association between RCCEP occurrence with higher objective response rate was observed (19.3% vs. 5.6%; one-sided p = 0.0044). Compared with those without RCCEP, patients with RCCEP had prolonged progression-free survival (median PFS; 3.2 months vs. 1.9 months; one-sided p < 0.0001) and overall survival (median OS; 17.0 months vs. 5.8 months; one-sided p < 0.0001). In multivariable analyses, the development of RCCEP was significantly associated with prolonged PFS and OS after adjusting for baseline covariates. In addition, the landmark analyses of PFS and OS were consistent with the unadjusted analysis. Conclusions RCCEP occurred on the skin surface and was an immune response of skin capillary endothelial cells. RCCEP occurrence positively associated with outcomes of camrelizumab in advanced HCC.

New media is a scientific and technological product under the background of the new era, and now new media technology has been widely used in all aspects of social development, and it has spawned the arrival of the new media era. In the new media environment, the survival and development environment faced by enterprises have undergone earth-shaking changes; if you still follow the traditional marketing methods, it will not only reduce the effectiveness of marketing but also because of the deviation from the development requirements of the times be eliminated, bringing threats to the survival and development of enterprises. The development of new media, represented by the Internet and mobile phones, has brought great changes to various industries in the world including tourism. The market size of the travel network is expanding, and online sales are soaring. At the same time, all kinds of tourism organizations often have blind optimism in the construction of tourism networks and lack of reasonable application means, so that tourism network marketing is far from exerting its potential in reality; on the one hand, it cannot provide transaction services that satisfy both supply and demand; on the other hand, it also affects the economic benefits of tourism organizations. Compared with the rapid development of the tourism media industry, the theoretical research related to the actual situation lags significantly. Although the number of related studies at home and abroad is increasing, most of them stay at the level of explanation and introduction, and the analysis of the tourism industry chain is not enough. The breadth and depth of the study are sorely lacking. The future letter needs to summarize the successes and failures of the development of the tourism media industry from a theoretical height and carry out theoretical improvement to guide practice, and it also needs to strengthen forward-looking research, summarize the laws and models, and put forward practical implementation plans to improve the overall development level of the tourism and media industry. Aiming at the problem of new media marketing strategy in shopping tourism scenic spots, this paper applies descriptive research, questionnaire survey, statistical processing, mathematical model, and other research methods to analyze the characteristics of new media such as prominence of personalization, increased audience selectivity, and diversified forms of expression presented by new media compared with traditional media, as well as the differences between the two in terms of communication status, dominant state, and audience state. 4I Marketing theory is applied to new media marketing, the changes in the marketing environment and marketing needs under the background of new media, and the extensive impact of these changes on the marketing mix strategy; the basic strategies and expected effects of new media marketing of tourism enterprises are studied from the aspects of product, price, channel, and promotion; the IPA model is constructed, and the empirical analysis of the shopping tourist attractions of Changshu Garment City in China is carried out. Through the research of this paper, in theory, the understanding of new media marketing is enriched, and in fact, it provides guidance for optimizing the new media marketing strategy of tourist attractions.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. Bu-Shen-Tong-Du prescription (BSP) has traditionally been used in to treat RA but its underlying mechanisms remain unclear. In this study, we explored the potential mechanisms of BSP in collagen-induced arthritis (CIA) rats, a classic animal model of RA. We employed an integrated pharmacology approach in combination with network pharmacology, 1H-nuclear magnetic resonance (NMR) metabolomics, and biochemical analyses to determine the mechanisms of BSP for treating RA. We found that BSP can regulate immunity and inflammation by decreasing the spleen index; inhibiting hyperplasia of the white pulp; reducing the levels of IL-1β, IL-6, IL-17A, and IFN-γ; and increasing the levels of IL-10 in the serum. Network pharmacology was utilized to predict related signal transduction pathways of BSP in RA treatment. 1H NMR metabolomics of the serum confirmed that BSP regulated energy metabolism and amino acid metabolism. Finally, we validated the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway using immunohistochemical methods, which demonstrated that BSP controlled RA-induced inflammation by inhibiting the TLR4/NF-κB signaling pathway. These results confirm the therapeutic effect of BSP in a CIA rat model, which is exerted via the inhibition of the inflammation and the improvement of the immune function, balancing energy metabolism and amino acid metabolism, and inhibiting the TLR4/NF-κB signaling pathway. This study provides an experimental basis for using BSP as a combinatorial drug to inhibit inflammation and regulate immunity in the treatment of RA.

Kawasaki disease is an acute, self-limiting vasculitis in children. Early treatment is necessary to prevent cardiovascular complications. The acute phase of Kawasaki disease may present with hemodynamic instability. An association between viral respiratory infections and Kawasaki disease has been reported. Studies have shown that Kawasaki and Kawasaki-like disease may be associated with and have symptoms overlapping COVID-19. Children with COVID-19 may present as Kawasaki-like disease with pediatric inflammatory multisystem syndrome, or macrophage activation syndrome. Clinicians need to be aware of the early diagnosis and management of Kawasaki disease to prevent the development of coronary artery aneurysms. The symptoms overlap of multisystem inflammatory disease seen in COVID-19 adds to the difficulties in timely diagnosis and treatment. Children with Kawasaki disease require regular follow-up plans for coronary artery aneurysms. This adds to the difficulties during the changed environment of COVID-19 for control and prevention. Missed diagnosis and early treatment of Kawasaki disease with immunoglobulin and aspirin results in the development of coronary artery aneurysm in up to 25% of cases, with grave consequences. Here, we briefly review the management of typical and atypical Kawasaki disease which has symptoms overlapping with the multisystem inflammatory disease as seen in COVID-19.

Background Emerging clinical data suggest that an immune checkpoint inhibitor in combination with an antiangiogenic agent is a reasonable strategy for multiple malignancies. We assessed the combination of camrelizumab with apatinib in pretreated advanced primary liver cancer (PLC, cohort A) from a multicohort phase Ib/II trial.Methods Patients with PLC after prior systemic treatment(s) were administered camrelizumab (3 mg/kg, once every 2 weeks) plus apatinib (125, 250, 375, or 500 mg; once per day) in a 3+3 dose-escalation stage and subsequent expansion stage. The primary endpoints were tolerability and safety of study treatment.Results From April 2017 to July 2019, 28 patients (21 with hepatocellular carcinoma and 7 with intrahepatic cholangiocarcinoma) received camrelizumab plus apatinib. Two dose-limiting toxicities (both grade 3 diarrhea) were reported in the 500 mg cohort. Therefore, the 375 mg cohort was expanded. Of the 19 patients in the 375 mg cohort, dose reduction to 250 mg occurred in 8 patients within 2 months after treatment initiation. Of the 28 patients with PLC, 26 had grade ≥3 treatment-related adverse events, with hypertension being the most common (9/28). One treatment-related death occurred. The objective response rate was 10.7% (95% CI 2.3% to 28.2%). Median progression-free survival and overall survival were 3.7 months (95% CI 2.0 to 5.8) and 13.2 months (95% CI 8.9 to not reached), respectively.Conclusion The combination of camrelizumab with apatinib had a manageable toxicity and promising antitumor activity in patients with advanced PLC. Apatinib at a dose of 250 mg is recommended as a combination therapy for further studies of advanced PLC treatment.Trial registration numbers NCT03092895.

Currently, anti-obesity drugs are limited by their high costs and numerous adverse effects. In this study, collagen peptide (CP), with molecular weights ranging from 500 to 5000, was enzymatically hydrolyzed using Walleye pollock skin. We further demonstrated the effective anti-obesity effects of CP in a High-Fat Diet-Fed Mice. The microbial analysis showed that CP treatment could regulate the overall composition of the gut microbiota. Specifically, CP intervention increased the relative abundance of Lactobacillus, Akkermansia, Parabacteroides, and Odoribacter spp. CP intervention decreased the abundance of intestinal inflammation bacteria, such as Erysipelatoclostridium and Alistipes. To the best of our knowledge, this study was the first of its kind to provide evidence that CP could restore the composition of the gut microbiota destroyed in the HFD mouse model. These results indicate that CP from Walleye pollock skin is a potential agent for further development as an adjuvant treatment for obesity and related metabolic diseases.

Oligoalginate lyases catalyze the degradation of alginate polymers and oligomers into monomers, a prerequisite for biotechnological utilizing alginate. In this study, we report the cloning, expression and biochemical characterization of a new polysaccharide lyase (PL) family 17 oligoalginate lyase, OalV17, from the marine bacterium Vibrio sp. SY01. The recombinant OalV17 showed metal ion independent and detergent resistant properties. Furthermore, OalV17 is an exo-type enzyme that yields alginate monomers as the main product and recognizes alginate disaccharides as the minimal substrate. Site-directed mutagenesis followed by kinetic analysis indicates that the residue Arg231 plays a key role in substrate specificity. Furthermore, a rapid and efficient alginate monomer-producing method was developed directly from Laminaria japonica. These results suggest that OalV17 is a potential candidate for saccharification of alginate.

Here we isolated and characterized the complete mitochondrial genome of the hybrid grouper (Cromileptes altivelis♀ × Epinephelus tukula♂). It is 16,503 bp long and contains 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and a control region. The nucleotide composition is 29.08% of A, 29.03% of C, 15.66% of G and 26.23% of T, with 55.31% A + T. The phylogenetic analysis by neighbor-joining (NJ) method reveals that the hybrid offspring has a closer relationship to C. altivelis.

Many studies widely used SiO2@Ag composite nanospheres for surface enhanced Raman scattering (SERS), which mainly contributes to electromagnetic enhancement. In addition to experiments, previous simulations mostly adopted a two-dimensional model in SERS research, resulting in the three-dimensional information being folded and masked. In this paper, we adopted the three-dimensional model to simulate the electric field distribution of SiO2@Ag composite nanospheres. It is found that when the Ag nanoparticles are distributed densely on the surface of SiO2 nanospheres, light cannot pass through the upper hemisphere due to the local surface plasmon resonance (LSPR) of the Ag nanoparticles, resulting in the upper hemisphere shielding effect; and if there are no Ag nanoparticles distributed densely on the surface of SiO2 nanospheres, the strong LSPR cannot be formed, so the incident light will be guided downward through the whispering gallery mode of the spherical structure. At the same time, we designed relevant experiments to synthesize SiO2@Ag composite nanosphere as SERS substrate and used Rhodamine 6G as a probe molecule to study its SERS performance. This design achieved a significant SERS effect, and is very consistent with our simulation results.

Abstract Background While the demand for the health service keeps escalating at the grass root or rural areas of China, a substantial portion of healthcare resources remains stagnant in the more developed cities and this has entrenched health inequity in many parts of China. At its conception, the Deepening Health Care Reform in 2012 China was intended to flush out these discrepancies and promote a more equitable and efficient distribution of health resources. Nearly half a decade of this reform, there are uncertainties as to whether the attainment of the objectives of the reform is in sight. Methods We divided Jiangsu Province into 3 zones according to the level of economic and social development i.e. developed, developing, and undeveloped areas. Using a hybrid of Panel data analysis and an augmented Data Envelopment Analysis (DEA), we model human resources, capital inputs of Community Health Centers to comprehensively determine the technical and scale efficiency of community health resources in 3 zones in Jiangsu Province. Results We sampled data and analysed efficiency and productivity growth of 75 Community Health Centers in 13 cities of Jiangsu Province from 2011 to 2015, which shows that a significant productive growth among Community Health Centers between 2011 and 2015. Mirroring the behavior of Community Health Centers, technological progress was the underlying force for the growth and the deterioration in efficiency change was found. This can be credited partly to the Deepening Health Care Reform measures aimed at improving technology availability in health centers in sub-urban areas. The regional summary of the DEA result shows that the stage of economic development and the efficiency performance of hospital did not necessarily go hand in hand among the 3 zones of Jiangsu. Conclusions The government of China in general and Jiangsu province in particular could improve the efficiency of health resources allocation by improving the community health service system, rationalizing the allocation of health personnel, optimizing the allocation of material resources and enhancing the level of health of financial resources allocation.

The complete mitochondrial genome of hybrid grouper from Epinephelus awoara (♀) ×E. tukula (♂) was obtained by PCR amplification. The circular genome was 16,801 bp in length, consisting of 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and a control region (D-loop region). The overall base composition was as follows: A: 28.46%, T: 27.27%, C: 27.27%, G: 16.49%. The new results may provide valuable data for the genetic and taxonomic research on artificial hybrid grouper.

Battery lifetime prediction is a promising direction for the development of next-generation smart energy storage systems. However, complicated degradation mechanisms, different assembly processes, and various operation conditions of the batteries bring tremendous challenges to battery life prediction. In this work, charge/discharge data of 12 solid-state lithium polymer batteries were collected with cycle lives ranging from 71 to 213 cycles. The remaining useful life of these batteries was predicted by using a machine learning algorithm, called symbolic regression. After populations of breed, mutation, and evolution training, the test accuracy of the quantitative prediction of cycle life reached 87.9%. This study shows the great prospect of a data-driven machine learning algorithm in the prediction of solid-state battery lifetimes, and it provides a new approach for the batch classification, echelon utilization, and recycling of batteries.

Multidrug and Toxic Compound Extrusion (MATE) proteins are essential transporters that extrude metabolites and participate in plant development and the detoxification of toxins. Little is known about the MATE gene family in the Solanaceae, which includes species that produce a broad range of specialized metabolites. Here, we identified and analyzed the complement of MATE genes in pepper (Capsicum annuum) and potato (Solanum tuberosum). We classified all MATE genes into five groups based on their phylogenetic relationships and their gene and protein structures. Moreover, we discovered that tandem duplication contributed significantly to the expansion of the pepper MATE family, while both tandem and segmental duplications contributed to the expansion of the potato MATE family, indicating that MATEs took distinct evolutionary paths in these two Solanaceous species. Analysis of ω values showed that all potato and pepper MATE genes experienced purifying selection during evolution. In addition, collinearity analysis showed that MATE genes were highly conserved between pepper and potato. Analysis of cis-elements in MATE promoters and MATE expression patterns revealed that MATE proteins likely function in many stages of plant development, especially during fruit ripening, and when exposed to multiple stresses, consistent with the existence of functional differentiation between duplicated MATE genes. Together, our results lay the foundation for further characterization of pepper and potato MATE gene family members.

Membrane Attack Complex and Perforin (MACPF) proteins play crucial roles in plant development and plant responses to environmental stresses. To date, only four MACPF genes have been identified in Arabidopsis thaliana, and the functions of the MACPF gene family members in other plants, especially in important crop plants, such as the Poaceae family, remain largely unknown. In this study, we identified and analyzed 42 MACPF genes from six completely sequenced and well annotated species representing the major Poaceae clades. A phylogenetic analysis of MACPF genes resolved four groups, characterized by shared motif organizations and gene structures within each group. MACPF genes were unevenly distributed along the Poaceae chromosomes. Moreover, segmental duplications and dispersed duplication events may have played significant roles during MACPF gene family expansion and functional diversification in the Poaceae. In addition, phylogenomic synteny analysis revealed a high degree of conservation among the Poaceae MACPF genes. In particular, Group I, II, and III MACPF genes were exposed to strong purifying selection with different evolutionary rates. Temporal and spatial expression analyses suggested that Group III MACPF genes were highly expressed relative to the other groups. In addition, most MACPF genes were highly expressed in vegetative tissues and up-regulated by several biotic and abiotic stresses. Taken together, these findings provide valuable information for further functional characterization and phenotypic validation of the Poaceae MACPF gene family.

In practical decision-making, we prefer to characterize the uncertain problems with the hybrid data, which consists of various types of data, e.g., categorical data, numerical dada, interval-valued data and set-valued data. The extended rough sets can deal with single type of data based on specific binary relation, including the equivalence relation, neighborhood relation, partial order relation, tolerance relation, etc. However, the fusion of these relations is a significant challenge task in such composite information table. To tackle this issue, this paper proposes the intersection and union composite relation, and further introduces a quantitative composite decision-theoretic rough set model. Subsequently, we present a novel matrix-based approach to compute the upper and lower approximations in proposed model. Moreover, we propose the incremental updating mechanisms and algorithms under the addition and deletion of attributes. Finally, experimental valuations are conducted to illustrate the efficiency of proposed method and algorithms.

The hybrid offspring Epinephelus fuscoguttatus ♀ × E. tukula ♂ showed heterosis in terms of growth and disease resistance. The mitochondrial genome is 16,629 bp in length and consists of 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes, and a control region. The difference of total length is mainly caused by the difference of length in non-coding region. The nucleotide base composition is A = 29.15%, G = 15.62%, T = 26.91%, C = 28.32%, A + T = 56.06%, and C + G = 43.94%. The phylogenetic analysis using neighbour-joining (NJ) method showed that the hybrid offspring has a closer relationship to E. fuscoguttatus × E. lanceolatus.

Epinephelus akaara ♀ × Epinephelus tukula ♂ is an economically important fish. The mitochondrial genome of the hybrid grouper had a double-stranded DNA molecule with the length of 16,928 bp and consists of 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and a control region. The gene composition of the hybrid grouper mitochondrial genome was similar to that of most other vertebrates. Furthermore, phylogenetic analysis by maximum-likelihood (ML) method, based on the nucleotide sequences of 13 protein-coding genes, showed that the hybrid grouper has the closer relationship to Epinephelus akaara and confirmed that the mitochondrial genome is maternally inherited.

Objective(s):MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression. They have important roles in kidney development, homeostasis and disease, and participate in the onset and progression of tubulointerstitial sclerosis and end-stage glomerular lesions that occur in various forms of chronic kidney disease (CKD). In the present study, we elucidated the role of microRNA 205 (miR-205) in cisplatin-induced renal cell apoptosis and explored the molecular mechanisms. Materials and Methods:The chronic interstitial nephropathy rat model was induced, and the miRNA expression profile in the kidney cells from rats with CKD was screened. Cisplatin-induced apoptosis in normal renal HK-2 cells was evaluated using flow cytometry, and regulation of miR-205 on target gene was validated using luciferase assay, western blot and real time PCR assays. Results: We found that miR-205 expression was significantly decreased in the cells from kidney of CKD rat (P

Obesity and its related complications have become one of the leading problems affecting human health. However, current anti-obesity treatments are limited by high cost and numerous adverse effects. In this study, we investigated the use of a non-toxic green food additive, known as unsaturated alginate oligosaccharides (UAOS) from the enzymatic degradation of Laminaria japonicais, which showed effective anti-obesity effects in a high-fat diet (HFD) mouse model. Compared with acid hydrolyzed saturated alginate oligosaccharides (SAOS), UAOS significantly reduced body weight, serum lipid, including triacylglycerol (TG), total cholesterol (TC) and free fatty acids (FFA), liver weight, liver TG and TC, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels, adipose mass, reactive oxygen species (ROS) formation, and accumulation induced in HFD mice. Moreover, the structural differences in β-d-mannuronate (M) and its C5 epimer α-l-guluronate (G) did not cause significant functional differences. Meanwhile, UAOS significantly increased both AMP-activated protein kinase α (AMPKα) and acetyl-CoA carboxylase (ACC) phosphorylation in adipocytes, which indicated that UAOS had an anti-obesity effect mainly through AMPK signaling. Our results indicate that UAOS has the potential for further development as an adjuvant treatment for many metabolic diseases such as fatty liver, hypertriglyceridemia, and possibly diabetes.

Chitooligosaccharides (CHOS) have gained increasing attention because of their important biological activities. Enhancing the efficiency of CHOS production essentially requires screening of novel chitosanase with unique characteristics. Therefore, a rapid and efficient one-step affinity purification procedure plays important roles in screening native chitosanases. In this study, we report the design and synthesis of affinity resin for efficient purification of native chitosanases without any tags, using chitodisaccharides (CHDS) as an affinity ligand, to couple with Sepharose 6B via a spacer, cyanuric chloride. Based on the CHDS-modified affinity resin, a one-step affinity purification method was developed and optimized, and then applied to purify three typical glycoside hydrolase (GH) families: 46, 75, and 80 chitosanase. The three purified chitosanases were homogeneous with purities of greater than 95% and bioactivity recovery of more than 40%. Moreover, we also developed a rapid and efficient affinity purification procedure, in which tag-free chitosanase could be directly purified from supernatant of bacterial culture. The purified chitosanases samples using such a procedure had apparent homogeneity, with more than 90% purity and 10⁻50% yield. The novel purification methods established in this work can be applied to purify native chitosanases in various scales, such as laboratory and industrial scales.

The inflammatory response mediated by microglia plays a critical role in the progression of ischemic stroke. Phosphoinositide 3-kinase gamma (PI3Kγ) has been implicated in multiple inflammatory and autoimmune diseases, making it a promising target for therapeutic intervention. The aim of this study was to evaluate the efficacy of 8e, a hydrogen sulfide (H2S) releasing derivative of 3-n-butylphthalide (NBP), on brain damage and PI3Kγ signaling following cerebral ischemia injury. 8e significantly reduced sensorimotor deficits, focal infarction, brain edema and neural apoptosis at 72 h after transient middle cerebral artery occlusion (tMCAO). The NOX2 isoform of the NADPH oxidase family is considered a major enzymatic source of superoxide. We found that the release of superoxide, together with the expression of NOX2 subunits p47phox, p-p47phox, and the upstream PI3Kγ/AKT signaling were all down-regulated by 8e, both in the penumbral region of the rat brain and in the primary cultured microglia subjected to oxygen-glucose deprivation (OGD). With the use of siRNA and pharmacological inhibitors, we further demonstrated that 8e regulates the formation of superoxide in activated microglia through the PI3Kγ/AKT/NOX2 signaling pathway and subsequently prevents neuronal death in neighboring neurons. Our experimental data indicate that 8e is a potential candidate for the treatment of ischemic stroke and PI3Kγ-mediated neuroinflammation.

Metalloproteases are emerging as useful agents in the treatment of many diseases including arthritis, cancer, cardiovascular diseases, and fibrosis. Studies that could shed light on the metalloprotease pharmaceutical applications require the pure enzyme. Here, we reported the structure-based design and synthesis of the affinity medium for the efficient purification of metalloprotease using the 4-aminophenylboronic acid (4-APBA) as affinity ligand, which was coupled with Sepharose 6B via cyanuric chloride as spacer. The molecular docking analysis showed that the boron atom was interacting with the hydroxyl group of Ser176 residue, whereas the hydroxyl group of the boronic moiety is oriented toward Leu175 and His177 residues. In addition to the covalent bond between the boron atom and hydroxyl group of Ser176, the spacer between boronic acid derivatives and medium beads contributes to the formation of an enzyme-medium complex. With this synthesized medium, we developed and optimized a one-step purification procedure and applied it for the affinity purification of metalloproteases from three commercial enzyme products. The native metalloproteases were purified to high homogeneity with more than 95% purity. The novel purification method developed in this work provides new opportunities for scientific, industrial and pharmaceutical projects.

Unsaturated alginate disaccharides (UADs), enzymatically derived from the degradation of alginate polymers, are considered powerful antioxidants. In this study, a new high UAD-producing alginate lyase, AlySY08, has been purified from the marine bacterium Vibrio sp. SY08. AlySY08, with a molecular weight of about 33 kDa and a specific activity of 1070.2 U/mg, showed the highest activity at 40 °C in phosphate buffer at pH 7.6. The enzyme was stable over a broad pH range (6.0–9.0) and retained about 75% activity after incubation at 40 °C for 2 h. Moreover, the enzyme was active in the absence of salt ions and its activity was enhanced by the addition of NaCl and KCl. AlySY08 resulted in an endo-type alginate lyase that degrades both polyM and polyG blocks, yielding UADs as the main product (81.4% of total products). All these features made AlySY08 a promising candidate for industrial applications in the production of antioxidants from alginate polysaccharides.