Hazard evaluation of goaf based on DBO algorithm coupled with BP neural network.

China is rich in mineral resources, and problems of goaf formed in the process of resource exploitation are serious obstacle to the development of China's economic, so it is of great significance for the assessment and management of goafs. This paper introduces emerging dung beetle optimizer (DBO) algorithm and establishes DBO-BP (back-propagation) model, at the same time, it is compared with a series of heuristic algorithms coupled with BP neural network models: PSO (particle swarm optimization) - BP model, WOA (whale optimization algorithm) - BP model, and SSA (sparrow search algorithm) - BP model. Then they are applied to evaluate the hazard of goafs, the result shows that the DBO-BP model gets the highest train set accuracy, which is at least 2.7 % higher than other models, while the DBO-BP model obtains the highest test set accuracy, meanwhile its effectiveness and stability have also been proven. Finally we apply the established DBO-BP model to evaluate the hazard of the tungsten mine goaf of Yaogangshan in Hunan Province, and its excellent practicability was confirmed. This paper may provide a reference for the solution of nonlinear engineering problems.

Development and verification of a rapid detection method for adalimumab biological activity based on U937-NF-κB-Luc cell line / 中国生物制品学杂志

@#Objective To develop and verify a rapid detection method for the biological activity of adalimumab based on U937-NF-κB-Luc cell line. Methods Using U937-NF-κB-Luc cell line as the detection cells,a method for detecting the biological activity of adalimumab was developed based on luciferase luminescence principle. The method was optimized for the concentration of tumor necrosis factor-α(TNF-α)(160 ng/mL as initial concentration,2 times serial dilution,10dilutions),the initial concentration of antibody(2 000 ng/mL,2 times serial dilution,20 dilutions),the dilution multiple of antibody(1. 5,2,3,4 times),the inoculation amount(8 × 103,2 × 104,4 × 104,6 × 104cells/well)and the incubation time(0. 5,1,2,3 h),and verified for the specificity,accuracy,precision and linear range. The relative potency of five batches of adalimumab was detected by using the optimized method and TNF-α neutralization activity method based on L929cells respectively. Results The dose-response curve of adalimumab international standard showed a typical S-type,and the data complied with the four-parameter equation y =(A-D)/[1 +(x/C)B]+ D,R2> 0. 99. The optimum concentration of TNF-α was 5 ng/mL,the initial concentration of antibody was 800 ng/mL,the dilution ratio for adalimumab was 1∶2,the inoculation amount was 2 × 104cells/well,and the induction time was 2 h. Three therapeutic monoclonal antibodies of TNF-α target,such as adalimumab,obtained good dose-response curves,while therapeutic monoclonal antibodies of other non-TNF-α targets did not show this curve. The linear regression equation of the logarithmic value of theoretical potency and the logarithmic value of the corresponding measured potency had a slope of 1. 037,and the relative bias was within the range of ± 12%. The geometric coefficient of variation(GCV)of the relative titer measured value of each sample was less than20%. The theoretical potency ranged from 64% to 156%,showing a good linear relationship with the measured values,and the fitting linear regression equation was y = 1. 037 4 x-0. 023 7,R2= 0. 998 4. There was no significant difference in the relative potency measured results of five batches of adalimumab by the two methods(t = 1. 198,P = 0. 265 1). Conclusion The developed detection method for adalimumab biological activity based on U937-NF-κB-Luc cell line has good specificity,accuracy and precision with short time consumption(3 h),which can be used as a rapid evaluation method for the biological activity of adalimumab.

Activated Tim-3/Galectin-9 participated in the development of multiple myeloma by negatively regulating CD4 T cells.

The interaction between Tim-3 on T cells and its ligand Galectin-9 negatively regulates the cellular immune response. However, the regulation of Tim-3/Galectin-9 on CD4 T cell subsets in multiple myeloma (MM) remains unclear. The aim of this study was to investigate the relationship between the regulation of CD4 T cell subsets by the Tim-3/Galectin-9 pathway and clinical prognostic indicators in MM. Tim-3/Galectin-9 were detected by flow cytometry, PCR and ELISA in 60 MM patients and 40 healthy controls, and its correlation with clinical prognostic parameters was analyzed. The expressions of Tim-3 on CD4 T cells, Galectin-9 mRNA in PBMC and level of Galectin-9 protein in serum were significantly elevated in MM patients, especially those with poor prognostic indicators. In MM patients, Tim-3 was highly expressed on the surfaces of Th1, Th2, and Th17 cells, but lowly expressed on Treg. Moreover, level of cytokine IFN-γ in serum was negatively correlated with Tim-3+Th1 cell and Galectin-9mRNA, Galectin-9 protein level. In addition, cell culture experiments showed that the anti-tumor effect and the ability to secrete IFN-γ were restored by blocking the Tim-3/Galectin-9 pathway. In MM patients, Tim-3/Galectin-9 is elevated and associated with disease progression, by inhibiting the cytotoxic function of Th1, and also promoting Th2 and Th17 to be involved in immune escape of MM. Therefore, Tim-3/Galectin-9 may serve as a new immunotherapeutic target for MM patients.

Foliar application of strigolactones improves the desiccation tolerance, grain yield and water use efficiency in dryland wheat through modulation of non-hydraulic root signals and antioxidant defense.

Non-hydraulic root signals (nHRS) are affirmed as a unique positive response to soil drying, and play a crucial role in regulating water use efficiency and yield formation in dryland wheat production. Strigolactones (SLs) can enhance plant drought adaptability. However, the question of whether strigolactones enhance grain yield and water use efficiency by regulating nHRS and antioxidant defense systems in dryland wheat remains unanswered. In this study, pot experiments were conducted to investigate the effects of strigolactones on nHRS, antioxidant defense system, and grain yield and water use efficiency in dryland wheat. The results showed that external application of SLs increased drought-induced abscisic acid (ABA) accumulation and activated an earlier trigger of nHRS at 73.4% field capacity (FC), compared to 68.5% FC in the control group (CK). This phenomenon was mechanically associated with the physiological mediation of SLs. The application of SLs significantly enhanced the activities of leaf antioxidant enzymes, reduced ROS production, and mitigated oxidative damage to lipid membrane. Additionally, root biomass, root length density, and root to shoot ratio were increased under strigolactone treatment. Furthermore, exogenous application of SLs significantly increased grain yield by 34.9% under moderate drought stress. Water use efficiency was also increased by 21.5% and 33.3% under moderate and severe drought conditions respectively, compared to the control group (CK). The results suggested that the application of strigolactones triggered earlier drought-sensing mechanism and improved the antioxidant defense ability, thus enhancing grain yield and water use efficiency in dryland wheat production.

[Expression and Clinical Significance of Helper T Cells 9 and Its Sytokines Interleukin 9 in Chronic Lymphocytic Leukemia].

OBJECTIVE: To investigate the expression and clinical significance of T helper cell 9 (Th9) and its cytokine interleukin 9(IL-9) in peripheral blood of patients with chronic lymphocytic leukemia(CLL). METHODS: A total of 43 newly diagnosed patients with chronic lymphocytic leukemia in the First Affiliated Hospital of Xinjiang Medical University from June 2021 to June 2022 were selected as the case group. The patients were divided into Binet A group (13 cases), Binet B group (20 cases) and Binet C group (10 cases) by Binet staging system, and 20 healthy volunteers who underwent physical examinationin in our hospital in the same period served as control group. The proportion of Th9 cells in peripheral blood was detected by flow cytometry, the expression level of Th9 specific transcription factors PU.1 and IRF4 was detected by Western blot, and the expression level of serum cytokine IL-9 was detected by ELISA. The proportion of Th9, the expression of PU.1, IRF4 and IL-9 in each group were compared, and the correlation between the proportion of Th9, IL-9 and clinicopathological indexes of CLL patients was analyzed. RESULTS: The proportion of Th9, the expression of PU.1, IRF4 and IL-9 in CLL group were significantly higher than those in control group (P<0.05), the proportion of Th9 and the expression of IL-9 in Binet B and C group were higher than those in Binet A group (P<0.05), but there was no significant difference in the proportion of Th9 cells between Binet B group and C group (P>0.05). The expression of IL-9 in Binet C group was significantly higher than that in Binet B group (P<0.05) . The proportion of Th9 cells and IL-9 were highly expression in patients with ß2 microglobulin abnormality, IGHV unmutation, P53 abnormality and hepatosplenic lymph node enlargement(P<0.05), but not related to age and sex (P>0.05). The results of Spearman correlation analysis showed that the proportion of Th9 in patients with CLL was negatively correlated with the lymphocytic account and lymphocyte proportion(rs=-0.32，rs=-0.34). The proportion of Th9 and IL-9 were positively correlated with Binet stage, Rai stage and CLL-IPI Scoring (rs=0.79，rs=0.54，rs=0.58； rs=0.72，rs=0.63，rs=0.45), but not with WBC, CD4+ T cells and CD8+T cells (P>0.05). The proportion of Th9 was positively correlated with IL-9 (rs=0.53). CONCLUSION: Th9 cells and IL-9 are abnormally highly expressed in CLL, which is related to the poor prognosis of CLL.

Incidence of constipation and associated factors in the period of lockdown during COVID-19 pandemic: protocol for a systematic review and meta-analysis.

INTRODUCTION: The lifestyle and habit changes that have emerged as a result of quarantine measures may have had a negative impact on defecation habits. However, there is a lack of data on combined estimates of its occurrence and prevalence. METHODS AND ANALYSIS: We will conduct a systematic search for observational studies on PubMed/MEDLINE, Web of Science, Cochrane Library, EMBASE, CNKI, SinoMed, VIP China Science and Technology Journal database, Chinese Biomedical Databases and Wanfang Data. The search will include literature published from the inception of the databases to September 2022. Two authors will independently screen articles and extract data based on predefined inclusion and exclusion criteria. The risk of bias in the included studies will be evaluated using the Newcastle-Ottawa Scale for observational studies. Statistical analysis will be performed using Review Manager software V.5.4 and STATA V.16.0 software. Heterogeneity among studies will be assessed using the Q statistical test and I2 statistical tests. In case of significant heterogeneity, subgroup analysis and sensitivity analysis will be conducted to explore the source of heterogeneity. Sensitivity analyses will also be performed to assess the reliability of the study findings. If feasible, a meta-analysis will be conducted. Otherwise, a descriptive synthesis will be performed using a best-evidence synthesis approach. The primary outcome of interest will be the prevalence of constipation. The secondary outcomes will involve examining the association of risk factors. To evaluate potential publication bias, we will use both the Begg funnel plot and Egger's weighted regression statistics. Furthermore, to accurately assess the quality of evidence for our primary outcome, we will employ the Grading of Recommendations Assessment, Development and Evaluation system. ETHICS AND DISSEMINATION: This systematic review protocol will only consider published studies available in databases and will not include individual patient data. Therefore, ethical approval is not required, and the findings will be published in a peer-reviewed journal. PROSPER REGISTRATION NUMBER: CRD42022366176.

Establishing a novel and sensitive assay for bioactivity determination of anti-CD25 antibodies.

Anti-CD25 antibodies have been approved for renal transplantation and has been used prior to and during transplantation by the Food and Drug Administration (FDA). However, no reported bioassays have been reflected the mechanism of action (MOA) of anti-CD25 antibodies. Here, we describe the development and validation of a reporter gene assay (RGA) based on the engineered C8166-STAT5RE-Luc cells expressing endogenous IL-2 receptors and a STAT5-inducible element-driven firefly luciferase in C8166 cell lines. The RGA was fully validated according to the International Conference on the Harmonization of Technical Requirements for the Registration of Pharmaceuticals for the Human Use-Q2 (ICH-Q2). After optimization, the assay showed excellent specificity, linearity, accuracy, precision, and robustness. Due to the MOA relatedness and the excellent assay performance, the RGA is suitable for exploring the critical quality attributes (CQAs), release inspection, comparability and stability of anti-CD25 mAbs.

Melatonin effects on sleep quality of COVID-19 patients: a protocol for systematic review and meta-analysis of randomised controlled trials with trial sequential analysis.

INTRODUCTION: Sleep disturbance is one of the common complaints of patients with COVID-19 infection. Melatonin is a physiological indoleamine involved in circadian rhythm regulation and it is currently used for secondary sleep disorders caused by various diseases. Some clinical randomised controlled trials (RCTs) have obtained a small amount of evidence and controversial results in support of their therapeutic effect on sleep disorders, but no studies have summarised and evaluated RCTs in all current databases to obtain conclusive results. Therefore, the aim of this systematic review and meta-analysis was to determine the efficacy and safety of melatonin in the treatment of sleep disturbances in patients with COVID-19. METHODS AND ANALYSIS: We will search for RCT-type studies of melatonin in the treatment of sleep disturbances in patients with COVID-19. From inception to October 2022 will be available on PubMed/MEDLINE, Web of Science, Embase, CINAHL, PsycINFO, LILACS, SCOPUS, Cochrane Central Register of Controlled Trials, ICTRP, Wanfang Data, VIP database and CNKI, VIP database, China Biomedical Literature Database to search for eligible studies. There are no language and geographical restrictions. Two authors will independently screen and select eligible studies, assess methodological quality and perform data extraction. Two additional authors will independently extract data from each study. Then, meta-analysis will then be carried out using a fixed-effects or random-effects model, using the mean difference for continuous outcomes and the relative risk for dichotomous outcomes. Risk of bias assessment will be assessed using the Cochrane risk-of-bias tool. Heterogeneity between studies was assessed by Cochrane Q-test and I2. The quality of evidence for each outcome will be assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Funnel plots, Begg's test and Egger's test will be used to assess the risk of publication bias. Subgroup analysis, data synthesis, meta-analysis and overall incidence of adverse events will be performed using Review Manager V.5.4 software and Stata software. Trial sequential analysis will be performed if appropriate. ETHICS AND DISSEMINATION: This study is an extraction review of data from existing studies, and thus it is unnecessary to obtain ethical approval. The results of this systematic review will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022359221.

Glyceroglycolipids in marine algae: A review of their pharmacological activity.

Glyceroglycolipids are major metabolites of marine algae and have a wide range of applications in medicine, cosmetics, and chemistry research fields. They are located on the cell surface membranes. Together with glycoproteins and glycosaminoglycans, known as the glycocalyx, they play critical roles in multiple cellular functions and signal transduction and have several biological properties such as anti-oxidant and anti-inflammatory properties, anti-viral activity, and anti-tumor immunity. This article focused on the sources and pharmacological effects of glyceroglycolipids, which are naturally present in various marine algae, including planktonic algae and benthic algae, with the aim to highlight the promising potential of glyceroglycolipids in clinical treatment.

Salvianolic acid B from Salvia miltiorrhiza bunge: A potential antitumor agent.

Salvia miltiorrhiza Bunge (Lamiaceae) is a perennial herb widely found in China since ancient times with a high economic and medicinal value. Salvianolic acid B (Sal-B) is an important natural product derived from Salvia miltiorrhiza and this review summarizes the anticancer activity of Sal-B. Sal-B inhibits tumor growth and metastasis by targeting multiple cell signaling pathways. This review aims to review experimental studies to describe the possible anticancer mechanisms of Sal-B and confirm its potential as a therapeutic drug.

Ameliorating effects of electroacupuncture on the low-grade intestinal inflammation in rat model of diarrhea-predominant irritable bowel syndrome.

BACKGROUND AND AIM: We aim to investigate the effects and mechanisms of electroacupuncture (EA) at ST25 and ST37 on the intestinal low-grade inflammation (LGI) in rat model of Diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS: IBS-D model rats were established by acetic acid enema combined with restraint and tail clamping. Before EA intervention, they were divided into three groups: blank 1 group, blank 2 group, and IBS-D model group. Diarrhea symptoms and visceral pain sensitivity were evaluated. After constructed the model successfully, the remaining IBS-D model group rats were randomly divided into model group and EA group. Local intestinal inflammation (HE staining), changes of intestinal mucosa (occludin protein and microvascular diameter) were evaluated. Differences between two groups were compared using t-test or Mann-Whitney U-test. Differences among more than two groups were compared using one-way ANOVA or Kruskal-Wallis test. RESULTS: After modeling, the results of HE staining in intestinal tract of IBS-D model rats showed LGI. Compared with the model group, 4 h fecal moisture content (diarrhea index) and the AWR score were decreased in the EA group. The results of HE in EA group showed that the infiltration of intestinal inflammatory cells were alleviated. Additionally, EA significantly upregulated the expression of occludin protein and partially dilated the intestinal microvascular diameter. Pearson correlation analysis showed that the symptoms of IBS-D rats were correlated with the changes of intestinal mucosa. CONCLUSION: EA may treat intestinal LGI in IBS-D rats by upregulating the expression of occludin protein and dilating the intestinal microvascular diameter.

Efficacy and safety of acupuncture combined with Chinese herbal medicine traditional Chinese medicine for poststroke cognitive impairment: A protocol for a systematic review and meta-analysis.

BACKGROUND: Poststroke cognitive impairment (PSCI) is often secondary to poststroke, which is common in stroke patients, induced difficulty in rehabilitation and seriously affects their quality of life. Currently, effective treatments are still limited. Researches show that acupuncture combined with traditional Chinese medicine (TCM) has a good effect on PSCI. However, there is no consistent conclusion at present. Therefore, THE purpose of this study is to assess the effectiveness and safety of acupuncture combined with TCM in the treatment of PSCI. METHODS: We will search the following databases from inception to January, 2022: the Cochrane Library, PubMed, Embase, Medline, Web of Science, China National Knowledge Infrastructure, China Biology Medicine, Wan Fang data, and the Chinese Science and Technology Periodical Database. All randomized controlled trials eligible for acupuncture combined with TCM for PSCI will be included in this study. Study selection, data extraction, and quality assessment will be performed by 2 reviewers independently. Bias risk assessment and data synthesis will be performed using the Review Manager software (RevMan, version 5.3) and R (version 3.6.1) software. RESULTS: We will synthesize the current studies to evaluate the effectiveness and safety of acupuncture combined with TCM in the treatment of PSCI. CONCLUSION: The systematic review will provide a new paradigm for acupuncture combined with TCM in the intervention of PSCI, and further provide scientific evidence for the efficacy and safety of acupuncture combined with TCM in the treatment of PSCI. TRIAL REGISTRATION NUMBER: INPLASY202220062.

Finger printing human norovirus-like particles by capillary isoelectric focusing with whole column imaging detection.

Owing to the limitation of in vitro culture of human noroviruses (HuNoVs), the development of HuNoV vaccines has to depend on the self-assembling virus-like particles (VLPs) with capsid protein expression. The heterogeneity of artificial VLPs exert an impact on the immunogenicity, and should be considered as one of the factors in vaccine evaluation. In this study, we biochemically finger print the HuNoV VLPs with different genogroups, genotypes and sub-genotypes which constitute for a candidate vaccine, by using capillary isoelectric focusing with whole column imaging detection (cIEF-WCID). The electropherograms of GI.1, GII.3, GII.4 and GII.17 VLPs in fluorescence signal were described in the monomer VP1 forms after degenerated by 8 M urea. The four HuNoV VLPs showed different properties in electropherogram finger prints. The finger prints were also reproducible within a certain concentration range (approx. 150 ∼ 20 ug/ml). This method can also tell the changes of pI finger-print patterns when the expired HoNoV VLPs were tested. In conclusion, cIEF-WCID shows great promise for evaluating the production consistency of HuNoV VLP vaccine.

Bottom-up redistribution of biomass optimizes energy allocation, water use and yield formation in dryland wheat improvement.

BACKGROUND: Modern wheat cultivars have been developed having distinct advantages in many aspects under drought stress, such as plasticity in biomass allocation and root system architecture. A better understanding of the biomass allocation mechanisms that enable modern wheat to achieve higher yields and yield-based water use efficiency (WUEg ) is essential for implementing best management strategies and identifying phenotypic traits for cultivar improvement. We systematically investigated the biomass allocation, morphological and physiological characteristics of three ploidy wheat genotypes under 80% and 50% field water-holding capacity (FC) conditions. Some crucial traits were also assessed in a complementary field experiment. RESULTS: The diploid and tetraploid genotypes were found to allocate more biomass to the root system, especially roots in the topsoil under drought stress. Our data illustrated that lower WUEg and yield of these old genotypes were due to excessive investment in the root system, which was associated with severely restricted canopy development. Modern hexaploid genotypes were found to allocate smaller biomass to roots and larger biomass to shoots. This not only ensured the necessary water uptake, but also allowed the plant to distribute more assimilates and limited water to the shoots. Therefore, the hexaploid genotypes have evolved a stable plant canopy structure to optimize WUEg and grain yield. CONCLUSION: This study demonstrated that the biomass shift from below ground to above ground or a more balanced root:shoot ratio tended to optimize water use and yield of the modern cultivars. This discovery provides potential guidance for future dryland wheat breeding and sustainable management strategies. © 2021 Her Majesty the Queen in Right of Canada Journal of The Science of Food and Agriculture © 2021 Society of Chemical Industry. Reproduced with the permission of the Minister of Agriculture and Agri-Food Canada.

Quality comparability assessment of a SARS-CoV-2-neutralizing antibody across transient, mini-pool-derived and single-clone CHO cells.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a serious public health crisis worldwide, and considering the novelty of the disease, preventative and therapeutic measures alike are urgently needed. To accelerate such efforts, the development of JS016, a neutralizing monoclonal antibody directed against the SARS-CoV-2 spike protein, was expedited from a typical 12- to 18-month period to a 4-month period. During this process, transient Chinese hamster ovary cell lines are used to support preclinical, investigational new drug-enabling toxicology research, and early Chemistry, Manufacturing and Controls development; mini-pool materials to supply Phase 1 clinical trials; and a single-clone working cell bank for late-stage and pivotal clinical trials were successively adopted. Moreover, key process performance and product quality investigations using a series of orthogonal and state-of-the-art techniques were conducted to demonstrate the comparability of products manufactured using these three processes, and the results indicated that, despite observed variations in process performance, the primary and high-order structures, purity and impurity profiles, biological and immunological functions, and degradation behaviors under stress conditions were largely comparable. The study suggests that, in particular situations, this strategy can be adopted to accelerate the development of therapeutic biopharmaceuticals and their access to patients.

Subvisible Particle Analysis of 17 Monoclonal Antibodies Approved in China Using Flow Imaging and Light Obscuration.

In the study, subvisible particles in 205 samples from 17 commercial mAb drug products approved in China were analyzed using light obscuration (LO) and flow imaging microscopy (FIM) methods. For each method, a total 633 tests (runs) were performed. In the tests, samples in state of lyophilized powder or syringe package had significantly higher particle concentrations. It was confirmed by analyzing the 205 drug product samples that FIM particle counts are generally higher than LO counts. The cause of the higher counts of FIM method than LO counts was examined by looking into the contribution of proteinaceous, translucent particles in the samples. The data of the study showed that the number of proteinaceous, translucent particles was a factor in the elevated counts of FIM method compared to LO method.

Regulation of Mild Moxibustion on Uterine Vascular and Prostaglandin Contents in Primary Dysmenorrhea Rat Model.

OBJECTIVE: Primary dysmenorrhea (PD) is a common and high incidence disease in gynecology, which seriously affects the quality of life in young women. Our previous study found that mild moxibustion could treat abdominal pain of PD patients, but the mechanism is still unclear. Therefore, this study aims to partly investigate the treatment mechanism of moxibustion for PD, especially on uterine microcirculation. METHODS: Forty 3-month-old Sprague Dawley female rats were randomly divided into four groups, including group A (saline control group, n = 10), group B (control plus moxibustion group, n = 10), group C (PD model group, n = 10), group D (PD. model plus moxibustion group, n = 10). The PD rat model was established by injecting estradiol benzoate and oxytocin. Mild moxibustion on Sanyinjiao (SP6) and Guanyuan (CV4) acupoints was once a day, 20 minutes per time, for 10 consecutive days. A vaginal smear was used to test the estrous cycle of rats. Uterine microvascular thickness was observed by stereomicroscope. And we detected the content of prostaglandin F2α (PGF2α ) and prostaglandin E2 (PGE2) in uterine tissue by enzyme-linked immunosorbent assay. RESULTS: Mild moxibustion can enlarge the microvessels, improve the microcirculation disturbance, and relieve the swelling of the uterus in PD rats. During the mild moxibustion intervention, the contents of PGF2α and PGE2 in uterus issues were synchronous increases or decreases and the changes of PGE2 were more obvious, but the changes of uterine microvasculature and morphology caused by the decrease of PGF2α were greater than PGE2. CONCLUSION: Mild moxibustion at SP6 and CV4 acupoints may relax uterine microvascular obstacle by reducing the content of PGF2α in uterine tissue, improve the microcirculation disorder, and then alleviate the PD rat's uterine swelling.

Z-Shaped Transfer Functions for Binary Particle Swarm Optimization Algorithm.

Particle swarm optimization (PSO) algorithm is a swarm intelligent searching algorithm based on population that simulates the social behavior of birds, bees, or fish groups. The discrete binary particle swarm optimization (BPSO) algorithm maps the continuous search space to a binary space through a new transfer function, and the update process is designed to switch the position of the particles between 0 and 1 in the binary search space. Aiming at the existed BPSO algorithms which are easy to fall into the local optimum, a new Z-shaped probability transfer function is proposed to map the continuous search space to a binary space. By adopting nine typical benchmark functions, the proposed Z-probability transfer function and the V-shaped and S-shaped transfer functions are used to carry out the performance simulation experiments. The results show that the proposed Z-shaped probability transfer function improves the convergence speed and optimization accuracy of the BPSO algorithm.

ZmCCA1a on Chromosome 10 of Maize Delays Flowering of Arabidopsis thaliana.

Maize (Zea mays) is a major cereal crop that originated at low latitudes, and thus photoperiod sensitivity is an important barrier to the use of tropical/subtropical germplasm in temperate regions. However, studies of the mechanisms underlying circadian regulation in maize are at an early stage. In this study we cloned ZmCCA1a on chromosome 10 of maize by map-based cloning. The gene is homologous to the Myb transcription factor genes AtCCA1/AtLHY in Arabidopsis thaliana; the deduced Myb domain of ZmCCA1a showed high similarity with that of AtCCA1/AtLHY and ZmCCA1b. Transiently or constitutively expressed ZmCCA1a-YFPs were localized to nuclei of Arabidopsis mesophyll protoplasts, agroinfiltrated tobacco leaves, and leaf and root cells of transgenic seedlings of Arabidopsis thaliana. Unlike AtCCA1/AtLHY, ZmCCA1a did not form homodimers nor interact with ZmCCA1b. Transcripts of ZmCCA1a showed circadian rhythm with peak expression around sunrise in maize inbred lines CML288 (photoperiod sensitive) and Huangzao 4 (HZ4; photoperiod insensitive). Under short days, transcription of ZmCCA1a in CML288 and HZ4 was repressed compared with that under long days, whereas the effect of photoperiod on ZmCCA1a expression was moderate in HZ4. In ZmCCA1a-overexpressing A. thaliana (ZmCCA1a-ox) lines, the circadian rhythm was disrupted under constant light and flowering was delayed under long days, but the hypocotyl length was not affected. In addition, expression of endogenous AtCCA1/AtLHY and the downstream genes AtGI, AtCO, and AtFt was repressed in ZmCCA1a-ox seedlings. The present results suggest that the function of ZmCCA1a is similar, at least in part, to that of AtCCA1/AtLHY and ZmCCA1b, implying that ZmCCA1a is likely to be an important component of the circadian clock pathway in maize.

A robust and stable reporter gene bioassay for anti-IgE antibodies.

Immunoglobin E (IgE)-related allergy constitutes a high proportion in allergic diseases. The production of specific IgE is key to evoking serial cascades and pathological reactions. Thus, targeting IgE is a different therapeutic approach from symptomatic treatments. Monoclonal antibodies (mAbs) against IgE were developed and a humanized antibody, omalizumab, was approved by five countries. It could inhibit the binding of IgE with epsilon receptor I of crystallizable fragment (FcεRI), thus preventing anaphylactic reactions. However, no bioactivity assay, which is the critical quality attribute and should thoroughly reflect the clinical mechanism, has been established to date. In commercial lot release, only the enzyme-linked immunosorbent assay (ELISA) method was applied, which only reflects the binding of omalizumab to IgE but not the subsequent reaction. In scientific research works, human FcεRI-transfected RBL-2H3 cells were used to indicate degranulation based on the detection of ß-hexosaminidase. Nevertheless, this method needs much work to stabilize the response and, hence, is not suitable for routine usage in commercial production and control of antibodies. To evaluate the bioactivity of anti-IgE antibodies including omalizumab using a simple assay that reflects the following mechanism of actions (MOA) after binding, we established an RBL-2H3 cell line transfected with both the α subunit of human FcεRI and nuclear factor-activated T cell (NFAT) response elements, the latter is conjugated with a luciferase gene, which could shed luminescence when substrates exist. The method was proven to possess good specificity, accuracy, linearity, and precision and may be utilized as a supplement to anti-IgE antibody bioactivity assays in terms of development, lot release, stability, and comparability studies. Graphical abstract The mechanism sketch of reporter gene assay for bioactivity determination of anti-IgE antibodies by RBL-2H3/FcεRIα/NFAT-Luc cells (left) and representative curves generated by the reporter gene assay (right).