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Abstract Asymmetric division is a fundamental process for generating cell diversity and maintaining the stem cell population. During asymmetric division, proteins, organelles, and even RNA are distributed unequally between the two daughter cells, determining their distinct cell fates. The mechanisms orchestrating this process are extremely complex. Dysregulation of asymmetric division can potentially trigger cancer progression. Cancer stem cells, in particular, undergo asymmetric division, leading to intra-tumoral heterogeneity, which contributes to treatment refractoriness. In this review, we delve into the cellular and molecular mechanisms that govern asymmetric division and explore its relevance to tumorigenesis.

Immunotherapy has emerged as the primary treatment modality for patients with advanced Hepatocellular carcinoma (HCC). However, its clinical efficacy remains limited, benefiting only a subset of patients, while most exhibit immune tolerance and face a grim prognosis. The infiltration of immune cells plays a pivotal role in tumor initiation and progression. In this study, we conducted an analysis of immune cell infiltration patterns in HCC patients and observed a substantial proportion of CD8+T cells. Leveraging the weighted gene co-expression network analysis (WGCNA), we identified 235 genes associated with CD8+T cell and constructed a risk prediction model. In this model, HCC patients were stratified into a high-risk and low-risk group. Patients in the high-risk group exhibited a lower survival rate, predominantly presented with intermediate to advanced stages of cancer, displayed compromised immune function, showed limited responsiveness to immunotherapy, and demonstrated elevated expression levels of the Notch signaling pathway. Further examination of clinical samples demonstrated an upregulation of the Notch1+CD8+T cell exhaustion phenotype accompanied by impaired cytotoxicity and cytokine secretion functions that worsened with increasing Notch activation levels. Our study not only presents a prognostic model but also highlights the crucial involvement of the Notch pathway in CD8+T cell exhaustion—a potential target for future immunotherapeutic interventions.

Abstract As the full‐bridge modular multilevel converter (FB‐MMC) enables direct three‐phase AC voltage to single‐phase AC voltage conversion with good power quality and high voltage level, it is suitable for the co‐phase traction power supply system. However, voltage deviation occurs between arms when the direct AC/AC FB‐MMC operates in equal or similar frequency conditions. To solve this problem, a voltage balancing control based on third harmonic injection of co‐phase power supply system using direct AC/AC FB‐MMC is proposed. With the third harmonic injection, voltage balancing between arms is ensured and the capacity of FB‐MMC is enhanced. The third harmonic voltage is directly obtained from existing signals and the third harmonic current reference is produced by simple proportional‐integral (PI) controller. The effect of the third harmonic currents under different voltage ratios and phase difference is quantitatively analyzed, optimized range of voltage ratio and phase difference are obtained to minimize arm currents increment and reduce overrating of converter currents. In addition, a comparison between the proposed and the conventional control scheme is studied, showing the superior of proposed method in cost and performance. Finally, the effectiveness of the proposed scheme is verified by simulations and experiments.

Abstract Background and aim Although antiviral treatments have been shown to affect the recurrence and long-term survival of patients with hepatocellular carcinoma (HCC) who have high viral loads, the effect of different responses to antiviral therapy on the clinical outcomes remains unclear. This study aimed to assess the effect of primary non-response (no-PR) to antiviral therapy on the survival or prognosis of patients with HCC with a high load of hepatitis B virus (HBV) DNA. Methods A total of 493 HBV-HCC patients hospitalized at Beijing Ditan Hospital of Capital Medical University were admitted to this retrospective study. Patients were divided into two groups based on viral response (no-PR and primary response). Kaplan–Meier (KM) curves were used to compare the overall survival of the two cohorts. Serum viral load comparison and subgroup analysis were performed. Additionally, risk factors were screened and the risk score chart was created. Results This study consisted of 101 patients with no-PR and 392 patients with primary response. In the different categories based on hepatitis B e antigen and HBV DNA, no-PR group had a poor 1-year overall survival (OS). In addition, in the alanine aminotransferase

The study aimed to investigate the potential of traditional Chinese medicine (TCM) in reducing the risk of macrovascular invasion (MVI) in Chinese patients with hepatocellular carcinoma (HCC). This retrospective analysis involved 2,267 HCC patients treated at our hospital. Propensity score (PS) matching was used to compare TCM users (n = 485) with non-users (n = 485) in terms of age, Barcelona Clinic Liver Cancer (BCLC) staging, type of treatment, and AFP. The impact of TCM on the hazard ratio (HR) of MVI was evaluated using a Cox multivariate regression model. The efficacy of TCM therapy on MVI was further examined using the log-rank test. The analysis revealed that TCM medication was a significant protective factor for MVI in HCC patients, as evidenced by the Cox analysis (adjusted HR = 0.496, 95% CI: 0.387–0.635, p < 0.001). After PS matching, the Kaplan-Meier curve demonstrated a lower occurrence rate of MVI in TCM users compared to non-users. The study findings suggest that TCM treatment has the potential to decrease the incidence of MVI in HCC patients, irrespective of etiology, BCLC staging, liver function, or treatment type. Notably, as the use of TCM increased, the percentage of MVI in patients showed a gradual decrease, indicating the potential of TCM therapy as a successful strategy for preventing MVI.

Abstract Objective To identify the key drugs of Yangyin Fuzheng Jiedu prescription (YFJP) and investigate their therapeutic effects against hepatocellular carcinoma (HCC) and the potential mechanism using network pharmacology. Methods The H22 tumor‐bearing mouse model was established. Thirty male BALB/c mice were divided randomly into five groups. The mice were orally treated with either disassembled prescriptions of YFJP or saline solution continuously for 14 days. The mice were weighed every 2 days during treatment and the appearance of tumors was observed by photographing. The tumor inhibition rate and the spleen and thymus indexes were calculated. Hematoxylin and eosin and immunohistochemical staining were performed to observe the histological changes and tumor‐infiltrating lymphocytes. Cell apoptosis was determined by terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling staining. The proportion of CD8+ T cells and the expression of programmed cell death protein 1 (PD‐1), T cell immunoglobulin domain and mucin domain‐3 (Tim‐3), and T cell immunoreceptor with Ig and ITIM domains (TIGIT) were analyzed using flow cytometry. The production of serum cytokines was detected using the Milliplex® MAP mouse high sensitivity T cell panel kit. The active components of the key drugs and HCC‐related target proteins were obtained from the corresponding databases. The putative targets for HCC treatment were screened by target mapping, and potential active components were screened by constructing a component‐target network. The interactive targets of putative targets were obtained from the STRING database to construct the protein–protein interaction network. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes pathway enrichment analyses were performed based on potential targets. The gene–gene inner and component‐target‐pathway networks were constructed and analyzed to screen the key targets. Western blotting was used to evaluate the protein expression of the key targets in the tumor‐bearing mouse model. The binding activity of the key targets and compounds was verified by molecular docking. Results Among the three disassembled prescriptions of YFJP, the Fuzheng prescription (FZP) showed significant antitumor effects and inhibited weight loss during the treatment of H22 tumor‐bearing mice. FZP increased the immune organ index and the levels of CD8+ and CD3+ T cells in the spleen and peripheral blood of H22 tumor‐bearing mice. FZP also reduced the expression of PD‐1, TIGIT, and TIM3 in CD8+ T cells and the production of IL‐10, IL‐4, IL‐6, and IL‐1β. Network pharmacology and experimental validation showed that the key targets of FZP in the treatment of HCC were PIK3CA, TP53, MAPK1, MAPK3, and EGFR. The therapeutic effect on HCC was evaluated based on HCC‐related signaling pathways, including the PIK3‐Akt signaling pathway, PD‐L1 expression, and PD‐1 checkpoint pathway in cancer. GO enrichment analysis indicated that FZP positively regulated the molecular functions of transferases and kinases on the cell surface through membrane raft, membrane microarea, and other cell components to inhibit cell death and programmed cell death. Conclusion FZP was found to be the key disassembled prescription of YFJP that exerted antitumor and immunoregulatory effects against HCC. FZP alleviated T cell exhaustion and improved the immunosuppressive microenvironment via HCC‐related targets, pathways, and biological processes.

Abstract Background The number of young patients with hepatocellular carcinoma (HCC) is increasing, but whether patients of different ages have a survival advantage is unclear. This study was conducted to investigate whether age differences in the Barcelona Clinic Liver Cancer (BCLC) classification system contribute to the long-term survival outcomes of patients with HCC. Methods A total of 1602 patients with HCC admitted to the Beijing Ditan Hospital was included in this study. Patients were divided into younger (≤45 years) and older (> 45 years) groups. Factors determining overall survival and progression-free survival were analyzed using univariate and multivariate analyses with the Kaplan-Meier method and Cox proportional hazard regression model. We calculated the cumulative incidence function using the Fine-Gray model. The effect of mortality on age was also estimated using a restricted cubic spline. Results After matching, overall survival and progression-free survival were significantly better in younger patients than in older patients with BCLC stage 0-B (p = 0.015 and p = 0.017, respectively). In BCLC stage 0-B, all-cause mortality increased with age and increased rapidly around the age of 40 years (non-linear, p

Hepatocellular carcinoma (HCC) is a severe cancer endangering human health. We constructed a novel glycometabolism-related risk score to predict prognosis and immunotherapy strategies in HCC patients. The HCC data sets were obtained from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, and the glycometabolism-related gene sets were obtained from the Molecular Signature Database. The least absolute contraction and selection operator (LASSO) regression model was used to construct a risk score based on glycometabolism-related genes. A simple visual nomogram model with clinical indicators was constructed and its effectiveness in calibration, accuracy, and clinical value was evaluated. We also explored the correlation between glycometabolism-related risk scores and molecular pathways, immune cells, and functions. Patients in the low-risk group responded better to anti-CTLA-4 immune checkpoint treatment and benefited from immune checkpoint inhibitor (ICI) therapy. The study found that glycometabolism-related risk score can effectively distinguish the prognosis, molecular and immune-related characteristics of HCC patients, and may provide a new strategy for individualized treatment.

Abstract Background Alpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) (

Introduction: Among all immune cells, natural killer (NK) cells play an important role as the first line of defense against tumor. The purpose of our study is to observe whether the NK cell counts can predict the overall survival of patients with hepatocellular carcinoma (HCC). Methods: To develop a novel model, from January 2010 to June 2015, HCC patients enrolled in Beijing Ditan hospital were divided into training and validation cohort. Cox multiple regression analysis was used to analyze the independent risk factors for 1-year, 3-year and 5-year overall survival (OS) of patients with HCC, and the nomogram was used to establish the prediction model. In addition, the decision tree was established to verify the contribution of NK cell counts to the survival of patients with HCC. Results: The model used in predicting overall survival of HCC included six variables (namely, NK cell counts, albumin (ALB) level, alpha-fetoprotein (AFP) level, portal vein tumor thrombus (PVTT), tumor number and treatment). The C-index of nomogram model in HCC patients predicting 1-year, 3-year and 5-year overall survival was 0.858, 0.788 and 0.782 respectively, which was higher than tumor–lymph node–metastasis (TNM) staging system, Okuda, model for end-stage liver disease (MELD), MELD-Na, the Chinese University Prognostic Index (CUPI) and Japan Integrated Staging (JIS) scores (p < 0.001). The decision tree showed the specific 5-year OS probability of HCC patients under different risk factors, and found that NK cell counts were the third in the column contribution. Conclusions: Our study emphasizes the utility of NK cell counts for exploring interactions between long-term survival of HCC patients and predictor variables.

Abstract As an essential component of paraspeckles, nuclear paraspeckle assembly transcript 1 (NEAT1) localizes in the nucleus, promoting progression of various malignant solid tumors. Herein, an adverse effect of NEAT1 is reported, showing that the short isoform, NEAT1_1 suppresses acute myeloid leukemia (AML) development. NEAT1_1 is downregulated in leukemia stem cells (LSCs) and its decreased expression correlates with recurrence in AML patients. It is demonstrated that NEAT1_1 suppresses leukemogenesis and LSC function but is dispensable for normal hematopoiesis. Mechanistically, NEAT1_1 is released from the nucleus into the cytoplasm of AML cells, regulated by transcription factor C/EBPβ and nuclear protein NAP1L1. Cytoplasmic NEAT1_1 interacts with Wnt component DVL2 and E3 ubiquitin ligase Trim56, facilitates Trim56‐mediated DVL2 degradation, and thus suppresses Wnt signaling. Collectively, the findings show NEAT1_1 is translocated from the nucleus to the cytoplasm and acts as a tumor suppressor in AML.

Summary: CD146 is an adhesion molecule that plays important roles in angiogenesis, cancer metastasis, and immune response. It exists as a monomer or dimer on the cell surface. AA98 is a monoclonal antibody that binds to CD146, which abrogates the activation of CD146-mediated signaling pathways and shows inhibitory effects on tumor growth. However, how AA98 inhibits the function of CD146 remains unclear. Here, we describe a crystal structure of the CD146/AA98 Fab complex at a resolution of 2.8 Å. Monomeric CD146 is stabilized by AA98 Fab binding to the junction region of CD146 domains 4 and 5. A higher-affinity AA98 variant (here named HA98) was thus rationally designed. Better binding to CD146 and prominent inhibition on cell migration were achieved with HA98. Further experiments on xenografted melanoma in mice with HA98 revealed superior inhibitory effects on tumor growth to those of AA98, which suggested future applications of this antibody in cancer therapy.

Abstract VEGF-C is essential for lymphangiogenesis during development and tumor progression. VEGFR-3 is the well-known cognate receptor of VEGF-C to regulate lymphatic migration and proliferation, but the receptor of VEGF-C in regulating lymphatic sprouting, the initiating step of lymphangiogenesis, still remains elusive. Here we use both in vitro and in vivo methods to demonstrate CD146 as a receptor of VEGF-C to regulate lymphangiogenesis, especially at the sprouting step. Mechanistically, CD146 selectively activates the downstream p38 kinase, upon VEGF-C stimulation, to regulate lymphatic sprouting. Moreover, CD146 can also activate ERK to mediate VEGF-C regulation of the subsequent proliferation and migration of lymphatic endothelial cells. In zebrafish embryos, knockdown or dysfunction of CD146 results in similar developmental defects in lymphatic sprouting, capillary network, parachordal lymphangioblast (PL), and thoracic duct (TD) similar to down-regulation of VEGF-C. Altogether, our data reveals a critical role of CD146 to mediate VEGF-C signaling pathway in lymphangiogenesis.

Inflammation often induces regeneration to repair the tissue damage. However, chronic inflammation can transform temporary hyperplasia into a fertile ground for tumorigenesis. Here, we demonstrate that the microRNA miR-34a acts as a central safeguard to protect the inflammatory stem cell niche and reparative regeneration. Although playing little role in regular homeostasis, miR-34a deficiency leads to colon tumorigenesis after Citrobacter rodentium infection. miR-34a targets both immune and epithelial cells to restrain inflammation-induced stem cell proliferation. miR-34a targets Interleukin six receptor (IL-6R) and Interleukin 23 receptor (IL-23R) to suppress T helper 17 (Th17) cell differentiation and expansion, targets chemokine CCL22 to hinder Th17 cell recruitment to the colon epithelium, and targets an orphan receptor Interleukin 17 receptor D (IL-17RD) to inhibit IL-17-induced stem cell proliferation. Our study highlights the importance of microRNAs in protecting the stem cell niche during inflammation despite their lack of function in regular tissue homeostasis.

In this paper, we consider the singular $p$-Laplacian type equation $$displaylines{ -hbox{div}(|x|^{-eta} a(x, abla u)) =lambda f(x,u),quad hbox{in }Omega,cr u=0,quad hbox{on }partialOmega, }$$ where $0leqeta

Immunotherapy has emerged as the primary treatment modality for patients with advanced Hepatocellular carcinoma (HCC). However, its clinical efficacy remains limited, benefiting only a subset of patients, while most exhibit immune tolerance and face a grim prognosis. The infiltration of immune cells plays a pivotal role in tumor initiation and progression. In this study, we conducted an analysis of immune cell infiltration patterns in HCC patients and observed a substantial proportion of CD8+T cells. Leveraging the weighted gene co-expression network analysis (WGCNA), we identified 235 genes associated with CD8+T cell and constructed a risk prediction model. In this model, HCC patients were stratified into a high-risk and low-risk group. Patients in the high-risk group exhibited a lower survival rate, predominantly presented with intermediate to advanced stages of cancer, displayed compromised immune function, showed limited responsiveness to immunotherapy, and demonstrated elevated expression levels of the Notch signaling pathway. Further examination of clinical samples demonstrated an upregulation of the Notch1+CD8+T cell exhaustion phenotype accompanied by impaired cytotoxicity and cytokine secretion functions that worsened with increasing Notch activation levels. Our study not only presents a prognostic model but also highlights the crucial involvement of the Notch pathway in CD8+T cell exhaustion--a potential target for future immunotherapeutic interventions. [ABSTRACT FROM AUTHOR]

Abstract Background Lumbar spondylolysis is a bone defect in the pars interarticularis of the lumbar vertebral, which is a common cause of low back pain in youth. Although non-surgical treatment is a mainstream option, surgery is necessary for patients with persistent symptoms. Buck technique is widely used as a classical direct repair technique, but it cannot achieve reduction of low-grade spondylolisthesis and reconstruction of lumbosacral sagittal balance. We have described a novel surgical procedure based on Buck technique with temporary intersegmental pedicle screw fixation, and report a series of clinical outcomes in 5 patients to provide a reference for the clinical treatment of young lumbar spondylolysis. Methods Five young patients with symptomatic lumbar spondylolysis with a mean age of 19.20 ± 5.41 years underwent surgical treatment after an average of 7.60 ± 1.52 months of failure to respond to conservative treatment, using a new surgical procedure based on Buck technique combined with temporary intersegmental pedicle screw fixation. Results Five patients were successfully operated without serious complications such as nerve and vascular injury. The average operation time was 109.00 ± 7.42 min, the interpretative average blood loss was 148.00 ± 31.14 ml, and the average fusion time was 11.20 ± 1.64 months. All patients were followed up for 2 years after surgery, and the visual analogue score (VAS) of low back pain and Oswestry disability index (ODI) scores were significantly improved compared with those before surgery, and the Henderson’s evaluation were rated excellent or good. After the removal of the internal fixation, it was observed that temporary intersegmental fixation could repair the isthmus, reduce lumbar spondylolisthesis, and reconstruct the sagittal balance of the lumbosacral vertebrae while preserving lumbar motion and preventing intervertebral disc degeneration. Postoperative MRI indicated the Pfirrmann classification of the affected discs: 1 case from grade III to grade II, 3 cases from grade II to grade I, and 1 case remained grade II. Conclusions Buck technique supplemented by temporary intersegmental pedicle screw fixation is a highly applicable and effective method for the treatment of adolescent lumbar spondylolysis. The isthmic fusion is accurate, and temporary intersegmental fixation can effectively prevent disc degeneration and reconstruct the sagittal balance of lumbosacral vertebra.

Background: Broussonetia papyrifera (L.) L′Hér. ex Vent (B. papyrifera) is a deciduous tree widely distributed in Asia. Previous studies have revealed that leaves of B. papyrifera ameliorated atopic dermatitis (AD)-like symptoms and inflammatory response. However, the impact and underlying mechanism of other parts of B. papyrifera on AD remain elusive. Methods: The AD mice induced by 1-Chloro-2,4-dinitrochlorobenzene were used to observe the histopathological alterations in the skin tissues using hematoxylin-eosin staining and toluidine blue staining techniques. Serum levels of inflammatory factors were quantified utilizing ELISA. Pyroptosis was analyzed by lactate dehydrogenase release and flow cytometry in human keratinocytes. The activation of Nod-like receptor protein 3 (NLRP3) inflammasome was analyzed by western blots. Furthermore, the mechanism underlying the inhibition of NLRP3 inflammasome by N-butanol extracts of B. papyrifera root bark (NE-BPRB) was investigated using cellular thermal shift assay and surface plasmon resonance techniques. Results: Treatment with NE-BPRB significantly ameliorated symptoms of AD mice and reduced serum levels of pro-inflammatory factors. NE-BPRB intervention exhibited inhibitory effects on NLRP3 inflammasome activation and pyroptosis in vitro and in vivo. NE-BPRB and its primary bioactive constituent chlorogenic acid (CA) promote the K48-linked ubiquitination of NLRP3, leading to its proteasomal degradation by binding WW domain containing E3 ubiquitin protein ligase 1 (WWP1). Conclusions: The NE-BPRB and its primary bioactive constituent, CA, effectively inhibit the formation of the NLRP3 inflammasome and impede cell pyroptosis by promoting K48-linked ubiquitin-dependent proteasomal degradation of NLRP3 through binding to the E3 ubiquitin ligase WWP1, thereby resulting in improved AD.

Changes are occurred frequently during continuous integration. Existing testing methods often suffer from weak specificity or insufficiency when applied to continuous integration. To solve this problem, we implement a fuzzing tool called CIDFuzz for continuous integration. First, difference analysis is performed to locate the change points, and the distances between basic blocks and the change points are calculated. Then, the distances are instrumented into the program under test. During fuzz testing, testing resources are allocated according to the coverage of seeds to test the change points effectively.

Radiotherapy is a crucial treatment for head and neck malignancies, but it can sometimes cause sensorineural hearing loss (SNHL). Changes in the immune microenvironment and sensory neuroepithelium of the inner ear after radiation exposure remain poorly understood. This study investigated cochlear morphology and macrophages in the inner ear after high-dose irradiation. The heads of heterozygous 8-week-old Cx3cr1GFP/+ male mice were irradiated with 30Gy of X-rays and biological samples were collected on days 1, 7, and 10 after irradiation. Auditory brainstem responses were used to assess auditory function in the mice. Changes in basilar membrane hair cells, spiral ganglion neurons (SGN), and inner ear macrophages were observed using hematoxylin-eosin (HE) staining and immunofluorescence staining. The expression of inflammatory mediators in the inner ear was detected by quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) in cochlear tissue. The results showed no significant hair cell loss after a single high dose of radiation. However, the mice developed pantonal hearing loss on day 10 when HE staining revealed SGN atrophy and immunofluorescence showed decreased neurofilament expression. The number of macrophages in the inner ear reduced over time. RT-qPCR showed that cochlear inflammatory factors and chemokines were briefly upregulated on day 1st after irradiation and then decreased over time. In conclusion, high-dose irradiation causes acute SNHL that is not associated with hair cell loss and may be related to SGN changes. Radiation-induced SNHL is associated with a reduction in cochlear macrophages and changes in the immune microenvironment, but the relationship between the two remains to be investigated.

Objective: This systematic review investigates the long-term effect of cochlear implantation (CI) on clinical outcomes in tinnitus patients with sensorineural hearing loss (SNHL). Database Sources: PubMed, Embase, and the Cochrane Library were searched from inception to 30 April 2024. Manual searches of reference lists supplemented these searches when necessary. Review Methods: Original studies included in the meta-analysis had to contain comparative pre- and postoperative data for SNHL patients who underwent CI. Outcomes measured were the Tinnitus Handicap Inventory (THI), Visual Analog Scale (VAS), and Tinnitus Questionnaire (TQ). Results: A total of 28 studies comprising 853 patients showed significant tinnitus improvement after CI: THI mean difference (MD) −14.02 [95%CI −15.29 to −12.76, p < 0.001], TQ MD −15.85 [95%CI −18.97 to −12.74, p < 0.05], and VAS MD −3.12 [95%CI −3.49 to −2.76, p < 0.05]. Subgroup analysis indicated a significant difference between follow-up periods in THI (p < 0.0001) and VAS loudness (p = 0.02). Conclusions: Cochlear implantation substantially improves tinnitus in patients with hearing loss, though the effect may diminish over time. Further research is needed to confirm these findings.

In order to explore the optimum extraction process of polysaccharide and antioxidant activity in vitro in black corn kernel. In this study, black corn kernel was used as raw material, ultrasonic-assisted extraction was applied to extract polysaccharides from black corn kernel. To explore the effects of ultrasonic power, solid-liquid ratio, extraction time, temperature and frequency on the yield of polysaccharide. The extraction process of polysaccharide from black corn kernel was optimized by response surface methodology. Besides, the antioxidant activity of the polysaccharide was investigated by measuring its scavenging ability on DPPH·, ABTS+·, and ·OH. The results showed that the extraction yield of polysaccharide from black corn kernel could reach up to 41.09%±0.59%, in these conditions: The solid-liquid ratio was 1:20 g/mL, the extraction temperature was 74 ℃, the extraction time was 60 min and the extraction frequency was 3 times. The IC50 values of scavenging rates on DPPH·, ABTS+· and ·OH were 1.959, 1.529 and 0.3554 mg/mL, respectively. Moreover, the scavenging rates showed a certain dose-effect relationship with the sample concentration, indicating that the polysaccharide had a strong antioxidant activity, thus providing a theoretical basis for further research and utilization.

In this study, single factor experiments were employed to determine the effects of various factors on yields of total flavonoids and polyphenols from Broussonetia papyrifera root bark. Then Box-Behnken design and response surface methodology were used to optimize the ethanol reflux extraction process using the Design-Expert 11 software. Moreover, the antioxidant activity of the ethanol extract of Broussonetia papyrifera root bark was evaluated by determining the scavenging capacity of DPPH·, ABTS+·, and the hydroxyl free radical, as well as the total reducing power. Results showed that the optimal conditions were as follows: Extraction temperature 75 ℃, extraction time 117 min, solid-liquid ratio 1:16 g/mL, and ethanol concentration 70%. Under these conditions, the experimental extraction yield values of total flavonoids and polyphenols from Broussonetia papyrifera root bark were 23.93±0.30 mg/g and 14.69±0.56 mg/g, respectively, which was not significantly different in comparison to predicted values. The IC50 values of scavenging rates on DPPH·, ABTS+·, and the hydroxyl free radical were 5.256 μg/mL, 0.259 mg/mL, and 0.310 mg/mL, respectively, and the scavenging rates showed a certain dose-effect relationship with the sample concentration. In addition, the total reducing power of 1.0 mg/mL ethanol extract of the root bark was 1.484±0.062. These results indicated that this optimization test was effective and feasible, and the ethanol extract of Broussonetia papyrifera root bark had good antioxidant activity in vitro. The present study provides supplement information for the comprehensive utilization of Broussonetia papyrifera in food and medicine ingredients.

Abstract As agile software development and extreme programing have become increasingly popular, continuous integration (CI) has become a widely used collaborative work method. However, it is common to make changes frequently to a project during CI. If existing testing methods are applied to CI directly, it will be difficult to make testing resources focus on changes generated by CI, which results in insufficient testing for changes. To solve this problem, we propose a fuzz testing method for CI. First, differential analysis is performed to determine the change points generated during CI, change points are added to the taint source set, and static analysis is conducted to calculate the distances between each basic block and the taint sources. Then, the project under test is instrumented according to the distances. During fuzz testing, testing resources are allocated based on seed coverage to test the change points effectively. Using the proposed methods, we implement CIDFuzz as a prototype tool, and experiments are conducted on four open‐source projects that use CI. Experimental results show that, compared with AFL and AFLGo, CIDFuzz can reduce the time costs of covering change points up to 39.59% and 41.64%, respectively. Also, CIDFuzz can reduce the time costs of reproducing vulnerabilities up to 34.78% and 25.55%.

Cementing is a critical link in oil and gas exploitation, in which slurry density control is particularly important. In this study, we examined a slurry mixing control system in order to solve the problem of time delays in the mixing system. The model of a slurry mixing system was built in accordance with the system’s structure. A Smith fuzzy PID (proportion integration differentiation) composite control solution is proposed herein, and the simulation results show that the adjustment time and overshoot are lower than those of the conventional PID control and Smith predictive compensation control. A genetic algorithm is utilized to optimize the quantization factor and scale factor of the Smith fuzzy PID controller. Following optimization, the rise time of the controller was found to be 0.45 s, which represents a decrease of 35.9%, the overshoot was reduced by 0.4%, and the stabilization time was reduced by 36.6%. Afterward, we built a cementing slurry mixing simulation experimental platform, and experiments were used to verify the feasibility and superiority of the Smith fuzzy PID controller optimized by the genetic algorithm in comparison with the conventional controllers. The study results thus provide a scientific basis for the engineering application of the autonomous control technology of the slurry mixing system in cementing units.