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As one of the Analysis Centers (AC) of the International GNSS Service (IGS), Wuhan University (WHU) has been contributing to the IGS by providing ultra-rapid as well as rapid orbit and clock solutions for the established GPS and GLONASS since 2012. In the same year, the IGS initiated the Multi-GNSS Experiment (MGEX) to support the analysis of the emerging GNSS systems and prepare the IGS for Multi-GNSS, which includes GPS, GLONASS, the European Galileo system, the Chinese Beidou Navigation Satellite System (BDS), the Japanese Quasi-Zenith Satellite System (QZSS) and the Indian Regional Navigation Satellite System (IRNSS/NaVIC). The major products, i.e., orbits, Earth Orientation Parameters (EOPs), satellite clock as well as attitude have also been provided by WHU since 2012. More recently, WHU has engaged the third reprocessing of IGS for generating the highly accurate station coordinates as inputs for establishment of the International Terrestrial Reference Frame (ITRF) 2020 during 2019—2020. This article presents the recent major advancements of the IGS AC at Wuhan University, including precise products, real-time products, bias products, antenna phase center calibration, and the non-linear motion modeling for GNSS Reference Stations.

Quantifying the carbon budget in rice paddy ecosystems is fundamental to understanding the role of paddy fields as carbon sinks or sources and to mitigating global climate change. This study used a process‐based model of the denitrification‐decomposition (DNDC) model to estimate greenhouse gas (GHG) emissions and carbon sinks in the paddy ecosystem across China. The simulation results showed that the GHG emissions were 0.147 Pg C‐equivalent year−1 and that the carbon sequestration in rice plants and soils reached 0.253 Pg C year−1 in 2016, indicating high carbon sequestration potential of the Chinese paddy ecosystem. Land management had a great influence on carbon budgets, among which straw residue incorporation rate and nitrogen fertilizer applications had a stronger influence on carbon budgets, particularly for double cropping rice. These results indicate that appropriate tillage practices can reduce GHG emissions and increase carbon sequestration of rice ecosystems while ensuring rice yields. [ABSTRACT FROM AUTHOR]

Intracellular glutathione (GSH) is critical for cisplatin-resistant cancers by maintaining the redox balance. Amplifying the intracellular oxidative stress by disrupting the redox balance is an effective method for the treatment of cancers. Therefore, we design a mesoporous silica (MS) nanosystem coated by hyaluronic acid (HA) to codeliver l-buthionine sulfoximine (BSO) and cisplatin prodrug (DSCP) (defined as Pt/BSO-MS-HA). The intracellular GSH could react with DSCP in Pt/BSO-MS-HA, which could release free cisplatin for chemotherapy, and the BSO block the synthesis of GSH, leading to GSH depletion and disrupting the redox balance. Moreover, HA provides homotypic binding capacities and superior immune evasion, which significantly enhance the cell uptake of Pt/BSO-MS-HA and tumor accumulation. In in vivo studies, Pt/BSO-MS-HA could efficiently inhibit tumor growth and showed no obvious side effects. Our study provides an effective strategy to develop biocompatible drug delivery nanosystem by disrupting the redox balance in cancer cells, which significantly increase the therapeutic efficiency of cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Objective: BAT1706 is a proposed biosimilar of bevacizumab (BEV). The objective of this phase I clinical trial was to establish pairwise similarity between BAT1706, US-sourced BEV (US-BEV), and EU-sourced BEV (EU-BEV) after a single intravenous (IV) infusion in healthy male subjects. Methods: This phase I clinical trial was a randomized, double-blinded, three-arm study in 128 healthy adult male subjects. Every subject received a single IV infusion of 1 mg/kg of study drug and was subsequently monitored for 14 weeks. Pharmacokinetic, safety, and immunogenicity data were collected from each patient. The primary pharmacokinetic endpoint of this clinical study was area under the concentration curve from time zero to infinity (AUC0–inf). Biosimilarity of the study drugs was confirmed if the two-sided 90% confidence interval (CI) ratios of the geometric means for the three pairwise comparisons were contained within the range 80–125%. Other pharmacokinetic parameters including area under the concentration curve to time t (AUC0–t), maximum concentration of drug in plasma (Cmax), half-life (t½), and time to Cmax (tmax) were also measured. Results: The pharmacokinetic parameters were comparable for the three drug products evaluated. The 90% CI for the AUC0–inf was 99–112% for BAT1706 versus EU-BEV, 97–110% for BAT1706 vs US-BEV and 92–104% for EU-BEV versus US-BEV comparisons, respectively, demonstrating biosimilarity. There were no significant adverse events attributable to BAT1706, as compared to EU-BEV and US-BEV. BAT1706 demonstrated a similar safety profile to EU-BEV and US-BEV. In addition, no anti-drug antibody positive result was reported for any subject included in the study. Conclusion: In this study, BAT1706, a proposed biosimilar of BEV, was shown to be highly similar to EU-BEV and US-BEV in terms of pharmacokinetic equivalence, safety, and immunogenicity in healthy subjects after a single IV infusion. Trial Registration: NCT03030430. [ABSTRACT FROM AUTHOR]

Objectives: Salivary adenoid cystic carcinoma (SACC) is one of the most common malignant salivary gland tumors. Our study aims to investigate whether hypoxia‐induced autophagy was up‐regulated in the progression of SACC. Materials and methods: We performed differentially expressed gene analysis and pathway enrichment analysis and then calculated the correlation analysis on GSE59701 and GSE28996 datasets. The expression of HIF‐1ɑ and MAP1LC3B was analyzed in the paraffin‐embedded specimens by immunohistochemical method and in the hypoxic SACC‐LM cells by immunofluorescence. TEM microscopy was also performed to observe the formation of autophagosomes in SACC tissue and the hypoxic SACC‐LM cells. Results: The autophagy pathway was up‐regulated in SACC datasets, and five genes including MAP1LC3B were positively correlated with HIF‐1ɑ. Immunohistochemistry results showed that autophagy was activated and the expression of HIF‐1ɑ and MAP1LC3B was positively correlated in SACC specimens. In hypoxic SACC‐LM cells, we also identified the up‐regulation of autophagy and the close correlation between HIF‐1ɑ and MAP1LC3B expression. Autophagosomes were observed both in the tissue and the hypoxic SACC‐LM cells by TEM microscopy. Conclusions: Our study showed that autophagy is up‐regulated in dataset, SACC tissue, and hypoxic cell line; hypoxia‐induced autophagy in SACC might play a vital role in the development of SACC. [ABSTRACT FROM AUTHOR]

Objectives: Fibrous dysplasia (FD) is a focal bone lesion composed primarily of immature bone marrow stromal cells along with spicules of immature woven bone. However, cellular differentiation and proliferation in mutant human bone marrow stromal cells (hBMSCs) of FD have not been fully elucidated. Therefore, the aim of this study was to investigate the occurrence of Gsα mutation at the Arg201 codon in hBMSCs and human trabecular bone cells (hTBCs, osteoblast-like cells). In addition, we evaluated the gene expression and protein secretion of amphiregulin from hBMSCs and hTBCs and assessed the biologic activity and possible mechanism of amphiregulin in our system. Study design: Mutant hBMSCs from FD patients and hTBCs from disease-free bone specimens of the same patient were successfully cultured. We studied the Gsα mutations at the Arg201 codon by means of polymerase chain reaction (PCR)–restriction fragment length polymorphism. Gene expression and protein secretion of amphiregulin in hBMSCs and hTBCs was confirmed by reverse-transcription (RT) PCR and Western blotting analysis. The modulation proliferation and possible mechanism of the exogenous addition of amphiregulin and epidermal growth factor receptor tyrosine kinase inhibitor (AG-1478) were assessed by using Wst-1 assays. Results: The Gsα mutations in clonal adherent mutant hBMSCs and hTBCs were successfully identified. We identified amphiregulin to be highly expressed in hBMSCs compared with hTBCs. The growth of hBMSCs was stimulated by the exogenous addition of amphiregulin and inhibited by AG-1478. Conclusions: The Gsα-mutant hBMSCs were successfully identified, and amphiregulin may play a significant role in the proliferation of hBMSCs. [Copyright &y& Elsevier]

Impervious surfaces are key indicators for urbanization monitoring and watershed degradation assessment over space and time. However, most empirical studies only extracted impervious surface from spatial, temporal or spectral perspectives, paying less attention to integrating multiple dimensions in acquiring continuous changes in impervious surfaces. In this study, we proposed a neighborhood-based spatio-temporal filter (NSTF) to obtain the continuous change information of impervious surfaces from multi-temporal Landsat images in the Qinhuai River Basin (QRB), Jiangsu, China from 1988–2017, based on the results from semi-automatic decision tree classification. Moreover, we used the expansion intensity index (EII) and the landscape extension index (LEI) to further characterize the spatio-temporal characteristics of impervious surfaces on different spatial scales. The preliminary results showed that the overall accuracies of the final classification were about 95%, with the kappa coefficients ranging between 0.9 and 0.96. The QRB underwent rapid urbanization with the percentage of the impervious surfaces increasing from 2.72% in 1988 to 25.6% in 2017. Since 2006, the center of urbanization expansion was shaped from the urban built-up areas of Nanjing and Jiangning to non-urban built-up areas of the Jiangning, Lishui, and Jurong districts. The edge expansion occupied 73% on average among the different landscape expansion types, greatly beyond outlying (12%) and infilling (15%). The window size in the NSTF has a direct impact on the subsequent analysis. Our research could provide decision-making references for future urban planning and development in the similar basins. [ABSTRACT FROM AUTHOR]

In this paper, Thiele–Newton's blending expansion of a bivariate function is firstly suggested by means of combining Thiele's continued fraction in one variable with Taylor's polynomial expansion in another variable. Then, the Viscovatov-like algorithm is given for the computations of the coefficients of this rational expansion. Finally, a numerical experiment is presented to illustrate the practicability of the suggested algorithm. Henceforth, the Viscovatov-like algorithm has been considered as the imperative generalization to find out the coefficients of Thiele–Newton's blending expansion of a bivariate function. [ABSTRACT FROM AUTHOR]

In this paper, we expound on the hypergeometric series solutions for the second-order non-homogeneous k-hypergeometric differential equation with the polynomial term. The general solutions of this equation are obtained in the form of k-hypergeometric series based on the Frobenius method. Lastly, we employ the result of the theorem to find the solutions of several non-homogeneous k-hypergeometric differential equations. [ABSTRACT FROM AUTHOR]

In this paper, a few single-step iterative methods, including classical Newton's method and Halley's method, are suggested by applying [ 1 , n ] -order Padé approximation of function for finding the roots of nonlinear equations at first. In order to avoid the operation of high-order derivatives of function, we modify the presented methods with fourth-order convergence by using the approximants of the second derivative and third derivative, respectively. Thus, several modified two-step iterative methods are obtained for solving nonlinear equations, and the convergence of the variants is then analyzed that they are of the fourth-order convergence. Finally, numerical experiments are given to illustrate the practicability of the suggested variants. Henceforth, the variants with fourth-order convergence have been considered as the imperative improvements to find the roots of nonlinear equations. [ABSTRACT FROM AUTHOR]

In this paper, we present firstly several one-step iterative methods including classical Newton's method and Halley's method for root-finding problem based on Thiele's continued fraction. Secondly, by using approximants of the second derivative and the third derivative, we obtain an improved iterative method, which is not only two-step iterative method but also avoids calculating the higher derivatives of the function. Analysis of its convergence shows that the order of convergence of the modified iterative method is four for a simple root of the equation. Finally, to illustrate the efficiency and performance of the proposed method, we give some numerical experiments and comparison. [ABSTRACT FROM AUTHOR]

In the paper, we tackle the least squares estimators of the Vasicek-type model driven by sub-fractional Brownian motion: d X t = (μ + θ X t) d t + d S t H , t ≥ 0 with X 0 = 0 , where S H is a sub-fractional Brownian motion whose Hurst index H is greater than 1 2 , and μ ∈ R , θ ∈ R + are two unknown parameters. Based on the so-called continuous observations, we suggest the least square estimators of μ and θ and discuss the consistency and asymptotic distributions of the two estimators. [ABSTRACT FROM AUTHOR]

• NMR spectra infer the position of intermolecular hydrogen bonds in the selected DES. • The DES-UAE method was investigated to evaluate the quality of Herba Epimedii. • This method could effectively reduce solvent consumption and extraction time. • The optimal conditions were optimized by the orthogonal experimental design (OED). Deep eutectic solvent (DES) combined with ultrasound-assisted extraction (UAE) was successfully developed and fully validated to simultaneously determine Icarrin, IcarisidⅡ, Epimcdin A, Epimcdin B and Epimcdin C for the quality evaluation of Herba Epimedii. Twelve kinds of DESs were initially screened, and then the effective extraction was achieved by the tailor-made DES consisting of the mixture of l -proline and ethylene glycol with the molar ratio of 1:4 in this study. The optimal conditions were further optimized by the orthogonal experimental design (OED). 0.2 g sample powder was ultrasonic extracted by using 4.00 mL of aqueous solution containing 70 % (v/v) the above DES for 45 min, resulting to the optimum extraction efficiency. The FT-IR and NMR spectra showed the chemical structural characteristic correlation between l -proline and ethylene glycol, and could infer the formation of hydrogen bonds between the hydroxyl group of ethylene glycol and the nitrogen atom of l -proline. The hierarchical cluster analysis (HCA) was further processed for the quality evaluation of Herba Epimedii. Finally, DES could be used to distinguish different origins and different kinds of Herba Epimedii , and to evaluate the quality of Herba Epimedii. This method provided good linearity, precision and accuracy. The recoveries of the five main bioactive flavonoids in Herba Epimedii were within the range of 88.5–107.7 % (RSD less than 3.4 %). Compared to the traditional extraction method of Icarin in the Chinese Pharmacopoeia (2015 edition), the solvent consumption was decreased by 80 % and the extraction time was shortened by 25 %, leading to more efficient and more convenient of this DES-UAE method. This work indicated that DES would be a promising high effective solvent for the analytical sample preparations of plant herbs, and it might have a broad application in the quality control of traditional Chinese medicines. [ABSTRACT FROM AUTHOR]

In the post-COVID-19 era, the co-circulation of respiratory viruses, including influenza, SARS-CoV-2, and respiratory syncytial virus (RSV), continues to have significant health impacts and presents ongoing public health challenges. Vaccination remains the most effective measure for preventing viral infections. To address the concurrent circulation of these respiratory viruses, extensive efforts have been dedicated to the development of combined vaccines. These vaccines utilize a range of platforms, including mRNA-based vaccines, viral vector vaccines, and subunit vaccines, providing opportunities in addressing multiple pathogens at once. This review delves into the major advancements in the field of combined vaccine research, underscoring the strategic use of various platforms to tackle the simultaneous circulation of respiratory viruses effectively., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Wei, Liu, Li, Pan, Dai and Yang.)

OX40 (CD134), a member of the TNF receptor superfamily, is a widely studied costimulatory immune checkpoint. Several OX40 agonistic antibodies are in the clinical stage for cancer treatment, among which PF-04518600 is the leader and currently in phase II trial. It has been recognized that one potential mode of action for anti-OX40 antibodies is the deletion of intratumoral Tregs. Thus, a novel human anti-OX40 antibody, BAT6026, was generated with enhanced antibody dependent cellular cytotoxicity (ADCC) via fucose deletion to strengthen its Treg depletion activity. This characteristic of BAT6026 differentiates it from other previously reported anti-OX40 antibodies in the field of tumor therapy. The affinity of BT6026 to OX40 was 0.28nM, approximately 8 times stronger than that of PF-04518600. BAT6026 effectively competed for the binding of ligand OX40L to OX40, whereas PF-04518600 only partially competed. Moreover, compared to PF-04518600, BAT6026 activated T cells more effectively when clustered by FcγRs engagement and stimulated SEB-pretreated PBMCs to secrete IL-2 cytokines in vitro . In addition, BAT6026 demonstrated stronger anti-tumor activity than PF-04518600 in an OX40-humanized mouse MC38 tumor model. BAT6026 also showed a significantly synergistic effect on tumor inhibition when combined treatment with PD-1 antibody. Analysis of tumor-infiltrating T cells revealed that BAT6026 treatment significantly reduced Treg cells and increased CD8+ T cells in tumor. Preclinical safety assessment in non-human primates demonstrated a good safety profile for BAT6026. Together these data warrant further development of BAT6026 into clinical trials for patients with cancer., Competing Interests: All authors are employees of Bio-Thera Solutions Guangzhou, China. The authors declare that this study received funding from Bio-Thera Solutions. The funder had the following involvement in the study: study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication., (Copyright © 2023 Liang, Zheng, Liu, Mei, Zhou, Xiao, Qin, Yue, Lin, Liu, Li and Yu.)

Background : To compare the pharmacokinetic (PK) profile, safety, and immunogenicity between golimumab and the biosimilar BAT2506 in healthy Chinese male subjects. Research design and methods : A total of 180 healthy male subjects were recruited for this randomized, double-blinded, single-dose, parallel study. They received 50 mg BAT2506 or golimumab (1:1 ratio) by single subcutaneous injection. The evaluation index included maximum plasma concentration (C max ), area under the plasma concentration-time curve (AUC 0-t , AUC 0-∞ ), safety, and immunogenicity. Results : The results showed that the 90% confidence interval (CI) of the geometric mean ratio ( GMR ) of BAT2506 to reference drug (golimumab) for C max , AUC 0-∞ and AUC 0-t were 99.26% (90.59-108.76%), 102.06% (93.31%-111.64%), and 102.05% (93.51-111.38%), respectively. All 90% CIs were within the range of 80-125% range, which is the limitation of the equivalence margin. Furthermore, similarity of treatment-emergent adverse events was also found between the two drugs. A total of 14 subjects (7.8%) developed anti-drug antibody after administration. Conclusions : Our study confirmed the PK similarity between BAT2506 and golimumab, and showed good tolerance of BAT2506 in healthy subjects. There were no differences in safety and immunogenicity between the two drugs. Therefore, BAT2506 meets the criteria for biosimilarity to golimumab. Trial registration : The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04152759).

Objectives: Salivary adenoid cystic carcinoma (SACC) is one of the most common malignant salivary gland tumors. Our study aims to investigate whether hypoxia-induced autophagy was up-regulated in the progression of SACC., Materials and Methods: We performed differentially expressed gene analysis and pathway enrichment analysis and then calculated the correlation analysis on GSE59701 and GSE28996 datasets. The expression of HIF-1ɑ and MAP1LC3B was analyzed in the paraffin-embedded specimens by immunohistochemical method and in the hypoxic SACC-LM cells by immunofluorescence. TEM microscopy was also performed to observe the formation of autophagosomes in SACC tissue and the hypoxic SACC-LM cells., Results: The autophagy pathway was up-regulated in SACC datasets, and five genes including MAP1LC3B were positively correlated with HIF-1ɑ. Immunohistochemistry results showed that autophagy was activated and the expression of HIF-1ɑ and MAP1LC3B was positively correlated in SACC specimens. In hypoxic SACC-LM cells, we also identified the up-regulation of autophagy and the close correlation between HIF-1ɑ and MAP1LC3B expression. Autophagosomes were observed both in the tissue and the hypoxic SACC-LM cells by TEM microscopy., Conclusions: Our study showed that autophagy is up-regulated in dataset, SACC tissue, and hypoxic cell line; hypoxia-induced autophagy in SACC might play a vital role in the development of SACC., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)