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Background The pharmacokinetics, safety, and clinical activity of antibodies targeting CD22 have been evaluated in systemic lupus erythematosus (SLE) and non-Hodgkin lymphoma (NHL) patients, however, there have been no reports for the rheumatoid arthritis (RA) population. SM03 is a novel chimeric IgG1 monoclonal antibody which targets the B-cell-restricted antigen CD22. This is the first study of the anti-CD22 antibody in RA patients. Objectives This study was designed to preliminarily evaluate the pharmacokinetics, pharmacodynamics, safety, and clinical activity profiles of the anti-CD22 monoclonal antibody SM03 in Chinese patients with active RA. Materials and methods This study was an open phase I study in 8 RA patients. Eligible patients received two 600 mg doses of SM03 administered through intravenous infusions given 2 weeks apart and were monitored over an 84-day observation period for pharmacokinetics, pharmacodynamics, immunogenicity, safety, and clinical responses. Results After multiple doses of SM03, the maximum serum concentration of SM03 was reached within 2 - 4 hours. Mean elimination half-life was 16 days (range: 13 - 22 days). Half of the patients responded according to ACR and DAS28 assessments, and CD19+ B lymphocyte counts decreased. Upper respiratory tract infections and headaches were the most common adverse events (AEs). No drug-related serious AEs were reported. Conclusion This study is the first to report on the preliminary pharmacokinetics, pharmacodynamics, clinical activity, and safety of SM03 in RA patients. All AEs were mild or moderate in severity. SM03 showed potential efficacy in RA patients.

To explore the effect of meticulous nursing on postoperative recovery and adverse reactions of patients with benign prostatic hyperplasia (BPH) surgery. From February 2018 to February 2019, 104 patients with BPH who were diagnosed and treated in our hospital were selected. Forty-eight patients with BPH who received routine nursing were included in the routine nursing group (RNG). A total of 56 patients undergoing BPH surgery were included in the meticulous nursing group (MNG), who received meticulous nursing intervention on the basis of routine nursing. The scores of self-rating depression scale (BDI), self-rating anxiety scale (BAI), Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD), quality of life, complications and nursing satisfaction were compared between the two groups after nursing. After nursing, the levels of BDI, BAI, HAMA and HAMD in both groups were obviously lower than those before nursing, and the differences were statistically significant (P

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COVID-19 is still spreading around the world, and the pandemic has awakened the public’s attention to environmental cleanliness. This article used an online survey for people living in Taiwan, and a total of 1206 valid questionnaires were collected in October 2021. According to the survey results of Taiwanese people’s awareness of and needs for epidemic prevention and IAQ, 94.4% of the respondents agreed that maintaining IAQ during the COVID-19 pandemic is very important for prevention. In addition, 95.4% of them also pointed out that the “Clean and Safe” mark certification should be promoted in public places. Finally, this article also uses hierarchical regression to analyze public perceptions of seven indoor places, including elevators, restaurants, dwellings, offices, gyms, kindergartens, and long-term care centers. The results found that: (1) from the perspective of epidemic prevention, improving IAQ through ventilation strategies could prevent the spread of the COVID-19 pandemic, and (2) from the perspective of promotion certification, the elevators, restaurants and offices could establish strengthened IAQ, dwellings, gyms and long-term care centers should emphasize the display of IAQ information in entrances and exits, and kindergartens should focus on increasing safety and reducing infection.

African swine fever (ASF), a fatal disease outbroken in China in August 2018, has widely attracted social concern especially in the information era. The occurrence of ASF led to an imbalance between supply and demand in pork and other meat markets. As a result, meat prices fluctuated greatly during the past year in 2019. To measure ASF quantitatively, the internet public concern index about ASF was created using web crawler methods. The relationships between ASF and meat prices were analyzed based on time-varying parameter vector auto-regressive (TVP-VAR) model. The results showed that there were some differences in the impact size, direction and duration of ASF on the prices of pork, chicken, beef and mutton, and the characteristics of time variability and heterogeneity were obvious. At the same time, the impact of ASF on meat prices is not consistent with the trend and degree of ASF. The impulse intensity is strongly correlated with the strength and duration of ASF, and it is generally weak in the early stage and much stronger in the middle and late periods. The results indicate that macro regulations, monitoring and early-warning system, standardizing production and circulation, and the public opinion monitoring and guidance about ASF should be given more attention in future to stabilize the market expectations and to promote a smooth functioning of the livestock markets.

Pomegranate flowers (PFs) were reported to possess various biological activities such as antidiabetic, anti-inflammatory and hepatoprotective activities, and using to treat diabetes. Although chemical constituents and pharmacological activities of PFs have been studied, unfortunately, there was no report on the pharmacokinetic profile of PFs in vivo. In this study, a selective high-performance liquid chromatography triple quadrupole tandem mass spectrometry (HPLC–QQQ–MS/MS) method was developed and validated for simultaneous quantification of four compounds (corilagin, ellagic acid, gallic acid and brevifolincarboxylic acid) in rat plasma after oral administration of PFs. The good linearity concentration ranges for the four analytes were from 2.5 to 3000 ng/mL with coefficient value R2 > 0.99 in calibration curves. The intra- and inter-day accuracy of the four analytes was in the range of 85.33–102.50%, with relative standard deviation (RSD) of

Iron-based alloy coatings were deposited on grey cast iron through plasma transfer arc welding. Results showed that the iron-based alloy coatings are composed of pearlite, martensite, austenite, an...

Fatty acid biosynthesis is essential for bacterial survival. Of these promising targets, β-ketoacyl-acyl carrier protein (ACP) synthase III (FabH) is the most attractive target. FabH would trigger the initiation of fatty acid biosynthesis and it is highly conserved among Gram-positive and -negative bacteria. A series of novel amide derivatives bearing dioxygenated rings were synthesized and developed as potent inhibitors of FabH. These compounds were determined by

This qualitative study examines how intergenerational learning contributed to academic motivation among students of different ages in the Florida College System, the state’s community college syste...

Lithium-sulfur (Li-S) batteries have been regarded as an important candidate for next-generation energy storage devices due to their low cost and high theoretical energy density. However, several f...

Three undescribed sesquineolignans, Ziziphusmps A-C (1-3) were isolated from the seeds of Ziziphus jujuba. their gross structure was identified by comprehensive spectroscopic analyses. The part relative configurations were determined by the NOESY correlation and coupling constant. All isolates were tested for their cytotoxicity against the hepatocellular carcinoma Hep3B and HepG2 cells. The results indicated that none of them exhibited obvious cytotoxicity against two hepatocellular carcinoma cell lines.

Objective: To use high-frequency ultrasound to evaluate the efficacy of α-lipoic acid combined with traditional Chinese medicine in the treatment of diabetic peripheral neuropathy (DPN), so as to provide a basis for clinical medication and evaluation of therapeutic effect. Methods: From December 2018 to December 2019, 110 patients with DPN who met the inclusion and exclusion criteria were divided into observation group and control group according to different treatment plans. The control group was treated with α-lipoic acid, and the observation group was treated with α-lipoic acid combined with traditional Chinese medicine encapsulation treatment, and used high-frequency ultrasound, nerve conduction velocity and serological examination to comprehensively evaluate the effectiveness of the two treatment methods. Results: The mean amplitude of glycemic excursions (MAGE) value of the observation group and the control group after treatment was significantly lower than before treatment (P

Pan-sharpening is an effective method to obtain high-resolution multispectral images by fusing panchromatic (PAN) images with fine spatial structure and low-resolution multispectral images with rich spectral information. In this article, a multiscale pan-sharpening method based on dynamic convolutional neural network is proposed. The filters in dynamic convolution are generated dynamically and locally by the filter generation network which is different from the standard convolution and strengthens the adaptivity of the network. The dynamic filters are adaptively changed according to the input images. The proposed multiscale dynamic convolutions extract detail feature of PAN image at different scales. Multiscale network structure is beneficial to obtain effective detail features. The weights obtained by the weight generation network are used to adjust the relationship among the detail features in each scale. The GeoEye-1, QuickBird, and WorldView-3 data are used to evaluate the performance of the proposed method. Compared with the widely used state-of-the-art pan-sharpening approaches, the experimental results demonstrate the superiority of the proposed method in terms of both objective quality indexes and visual performance.

The variations of single event transient (SET) pulse width of high-LET heavy ion irradiation in 16-nm-thick bulk silicon fin field-effect transistor (FinFET) inverter chains with different driven strengths are measured at different temperatures. Three-dimensional (3D) technology computer-aided design simulations are carried out to study the SET pulse width and saturation current varying with temperature. Experimental and simulation results indicate that the increase in temperature will enhance the parasitic bipolar effect of bulk FinFET technology, resulting in the increase of SET pulse width. On the other hand, the increase of inverter driven strength will change the layout topology, which has a complex influence on the SET temperature effects of FinFET inverter chains. The experimental and simulation results show that the device with the strongest driven strength has the least dependence on temperature.

Polysaccharides from the species of Boletaceae (Boletales, Agaricomycetes, Basidiomycota) are economically significant to both functional foods and medicinal industries. The crude polysaccharide from Butyriboletus pseudospeciosus (BPP) was prepared, and its physicochemical properties were characterized through the use of consecutive experimental apparatus, and its impact on the gut microbiota of Kunming mice was evaluated. Analyses of the structure characteristics revealed that BPP was mainly composed of Man, Glc, and Gal, possessing the pyranose ring and β/α-glycosidic linkages. TG analysis exhibited that BPP had great heat stability. The SEM observation performed demonstrated that BPP appeared with a rough, dense, and porous shape. Through the BPP intervention, the serum and fecal biochemical index in mice can be improved obviously (p < 0.05). The abundance of beneficial microbiota in the BPP-treated group was significantly increased, while the abundance of harmful microbiota was significantly decreased (p < 0.05). Based on the Tax4Fun, we also revealed the relationship between the species of gut microbiota and showed that the high dose of BPP has significantly changed the functional diversities compared with those in other groups (p < 0.05). The results suggest that B. pseudospeciosus could serve as potential functional food or medicine.

Immune checkpoint inhibition is an important strategy in cancer therapy. Blockade of CTLA-4 and PD-1/PD-L1 is well developed in clinical practice. In the last few years, LAG-3 has received much interest as an emerging novel target in immunotherapy. It was recently reported that FGL1 is a major ligand of LAG-3, which is normally secreted by the liver but is upregulated in several human cancers. FGL1 is a crucial biomarker and target for cancer immunotherapy. As the efficacy of immunotherapy is limited to specific types of patients, the subset of patients needs to be selected appropriately to receive precise treatment according to different biomarkers. To date, there is no test to accurately assess FGL1 expression levels. Nanobodies have some outstanding features, such as high stability, solubility and affinity for diagnostic and therapeutic applications. Here, we report the development and validation of a rapid, sensitive, and cost-effective nanobody-based immunoassay for the detection of FGL1 in human serum. In this study, human FGL1 recombinant protein was expressed and purified for the first time as an immunized antigen. Then, we constructed a nanobody phage display library and screened several nanobodies that bind FGL1 with high affinity. We selected two nanobodies targeting different epitopes of FGL1, one as a capture and the other conjugated with HRP as a probe. The double nanobody-based sandwich ELISA to detect the concentration of FGL1 showed a good response relationship in the range of 15.625–2000 ng/mL, and the recoveries from the spiked sample were in the range of 78% and 100%. This assay could be used as a potential approach for evaluating FGL1 expression for patient stratification and for predicting the therapeutic efficacy of targeting the LAG3/FGL1 axis.

In mobile wireless sensor networks, localization accuracy and cost are the key issues to be considered. This paper is committed to solving the localization problem of mobile sensor networks. We propose an improved Black Hole (BH) algorithm based on compact strategy and elitist learning strategy. An improved Monte Carlo localization (IMCL) algorithm based on multi-hop combines the novel algorithm to deal with the localization problem of mobile sensor networks. The performance of the novel algorithm is verified on 28 test functions of CEC 2013 and compared with other standard optimization algorithms. The results reveal that the novel algorithm has first-class performance. In the simulation experiment, the novel algorithm and several optimization algorithms are applied to IMCL. The comparison results show that the new heuristic algorithm combined with IMCL can provide more competitive results in mobile node localization.

Background HL-085 is a selective, orally administered MEK1/2 inhibitor. We aimed to evaluate the safety and efficacy of HL-085 in patients with advanced melanoma harboring NRAS mutations. Methods This was a multicenter phase 1 study. HL-085 was administered twice daily in a standard 3 + 3 dose-escalation design (10 dose cohorts; 0.5–18 mg twice daily), followed by dose expansion at the recommended phase II dose (RP2D). The primary endpoints included tolerability, dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and RP2D. Results Between September 13, 2017, and January 18, 2021, 42 patients were enrolled (dose escalation phase: n = 30; dose expansion phase: n = 12). No DLT was reported during dose escalation and MTD was not reached with HL-085 doses up to 18 mg twice daily. The RP2D was 12 mg twice daily. The most common all-grade drug-related adverse events (AEs) across all dose levels were rash (61.9%), increased creatine phosphokinase (CK, 59.5%), face edema (50.0%), increased aspartate aminotransferase (47.6%), peripheral edema (40.5%), diarrhea (33.3%), alanine aminotransferase (33.3%), and paronychia (19.0%), most of which were grade 1 and 2. Most frequency of grade ≥ 3 AEs were CK (14.2%), asthenia (7.1%), peripheral edema (4.8%), and acneiform dermatitis (4.8%). In the cohort of 12 mg twice daily dose (15 patients), confirmed objective response rate was 26.7%; disease control rate was 86.7%; median duration of response was 2.9 months; median progression-free survival was 3.6 months. Conclusions The HL-085 showed acceptable tolerability and substantial clinical activity in patients with advanced melanoma harboring NRAS mutations. Trial registration Trial registration ClinicalTrials.gov number: NCT03973151.

Surface-enhanced Raman spectroscopy (SERS) is a powerful tool to monitor various interfacial behaviors providing molecular level information with high spatial and temporal resolutions. However, it is a challenge to obtain SERS spectra with high quality for analytes having a weak binding affinity with plasmonic nanostructures due to the short dwell time of the analyte on the surface. Here, we employed dynamic SERS, an acquisition method consisting of the rapid acquisition of a series of consecutive SERS spectra, to study the adsorption/desorption behavior of R6G on Ag surfaces. We demonstrated that the signal-noise ratio of SERS spectra of mobile molecules can be improved by dynamic SERS even when the acquisition time cannot catch up with the diffusion time of the molecule. More interestingly, we captured the neutral R6G0 state (spectroscopically different from the dominated positive R6G+ state) of R6G at the single-molecule level, which is a rare molecule event hardly detectable by traditional SERS. Dynamic SERS provides near real-time molecular vibrational information with an improved signal-noise ratio, which opens a new avenue to capture metastable or rare molecule events for the comprehensive understanding of interfacial processes related to catalysis and life science.

Aim: Dihydroartemisinin (DHA) was also found therapeutic potential for the treatment of systemic lupus erythematosus (SLE). To assess the pharmacokinetic profile of DHA, the concentration of DHA in plasma of SLE patients needed be accurately determined based on a rapid and reliable analytical method. Experimental method & results: Developed method utilizes stable isotope-labeled internal standards and SPE method for sample preparation, applied XBridge C18 column (2.1 × 50 mm, 3.5 μm) for chromatography separation. Detection of the analytes was achieved by an AB Sciex 4000 mass spectrometer under positive electrospray ionization mode. The method was validated in accordance with international guidelines on bioanalytical methods validations. Conclusion: DHA concentrations in human plasma of Chinese SLE patients were quantified by developed LC–MS/MS (no. 2016L02562).

International audience; Placobranchus ocellatus, regarded as a “solar-powered” sacoglossan mollusk, is well known to produce diverse and complex γ-pyrone polypropionates. Unexpectedly, in this study, the chemical investigation of P. ocellatus from the South China Sea led to the discovery of ocellatusones AD, a series of racemic non-γ-pyrone polyketides with novel skeletons, characterized by a bicyclo[3.2.1]octane (1, 2), a bicyclo[3.3.1]nonane (3) or a mesitylene-substituted dimethylfuran-3(2H)-one core (4). Extensive spectroscopic analysis, quantum chemical computation, chemical synthesis, and/or X-ray diffraction analysis were used to determine the structure and absolute configuration of the new compounds, including each enantiomer of racemic compounds 14 after chiral HPLC resolution. An important array of new and diversity-generating rearrangements is proposed to explain the biosynthesis of these unusual compounds based on careful structural analysis and comparison with six known co-occurring γ-pyrones (510). Furthermore, the successful biomimetic synthesis of ocellatusone A (1) from its γ-pyrone precursor (5) confirmed the biosynthetic relationship of these two compounds and the proposed rearrangement through an unprecedented acid promoted cascade reaction. Besides, an initially untargeted semisynthetic product, polycyclic lactone 11 with another novel carbocyclic skeleton was proved to be naturally occurring in the mollusk by comparative LC-MS/MS analysis, which provides a strategy to fish a vast number of novel trace components in Nature.

Aim: FLZ, a novel promising dopamine neuroprotective agent, is designed to treat Parkinson's disease. F7G and F21G are FLZ major active Phase II metabolites whose exposure are nearly 100-times higher than FLZ, may chiefly produce effectiveness in human. Measurement of F7G and F21G in plasma samples is critical for investigating its pharmacokinetics in clinical studies. Methodology & results: Plasma samples were extracted by SPE method and then analyzed by a newly established ultra-UHPLC–MS/MS method. Conclusion: For the first time, a reliable and robust bioanalytical method for F7G and F21G detection was successfully applied in a first-in-human study.

Various error sources exist in the specified relative permeability (kr) curves for numerical modeling of CO2/water core flooding process, including model selection, parameter estimation, and heterogeneity setting. In this study, we quantitatively investigate their effects on model predictions by a numerical sensitivity analysis. Numerical simulation results indicate: (1) The errors in residual gas saturation (Sgr) and residual liquid saturation (Slr) could significantly influence the estimation of the total volume (TPV) of injected CO2 when CO2/water displacement reaches a steady state. A change of Sgr or Slr by 0.1 can induce deviation in TPV up to 0.5 pore volume. (2) The change in Sgr could cause a bigger predictive deviation in local CO2 saturation (SCO2) than that in Slr. In the case of the same degree of change, the deviation of the former is almost twice as much as that of the latter. (3) The model predictions remain fairly consistent when utilizing either Corey's curve or Brooks–Corey curve, but become significantly different if changing to van Genuchten curve. In this case, the difference in TPV is greater than that caused by the errors in Sgr or Slr. The maximum deviation in the predicted local SCO2 exceeds 0.3, influencing the analysis of CO2 local trapping behavior. Comparatively, the local SCO2 buildup is only slight if van Genuchten curve is used, but obvious using Corey's curve. (4) kr heterogeneity only presents a small effect on the local SCO2 and could be reasonably ignored compared to the effects of the heterogeneity in capillary pressure and permeability. © 2020 Society of Chemical Industry and John Wiley & Sons, Ltd.

This paper proposes a novel hybrid algorithm named Adaptive Cat Swarm Optimization (ACSO). It combines the benefits of two swarm intelligence algorithms, CSO and APSO, and presents better search results. Firstly, some strategies are implemented to improve the performance of the proposed hybrid algorithm. The tracing radius of the cat group is limited, and the random number parameter r is adaptive adjusted. In addition, a scaling factor update method, called a memory factor y, is introduced into the proposed algorithm. They can be learnt very well so as to jump out of local optimums and speed up the global convergence. Secondly, by comparing the proposed algorithm with PSO, APSO, and CSO, 23 benchmark functions are verified by simulation experiments, which consists of unimodal, multimodal, and fixed-dimension multimodal. The results show the effectiveness and efficiency of the innovative hybrid algorithm. Lastly, the proposed ACSO is utilized to solve the Vehicle Routing Problem (VRP). Experimental findings also reveal the practicability of the ACSO through a comparison with certain existing methods.