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BackgroundSevere autoimmune haemolytic anaemia (AIHA) in systemic lupus erythematosus (SLE) patients could be life-threatening and formidable, especially in those nonresponsive to glucocorticoids (GCs) and immunosuppressants (ISAs). Whole-blood exchange transfusion (WBE), with plasma exchange and pathogenic cell removal as well as healthy red blood cell transfusion, could be beneficial. The objective of this study was to investigate the efficacy and safety of WBE in combination with GCs/ISAs.MethodsIn this retrospective study, the clinical data of 22 refractory severe SLE-AIHA inpatients between February 2016 and February 2021 were collected and analysed, among whom 14 patients had received WBE and were compared with those treated with typical second-line therapy of intravenous immunoglobulin and/or rituximab (IVIG/RTX).ResultsAmong the 22 severe refractory SLE-AIHA patients, eight patients received IVIG and/or RTX without WBE (group 1, IVIG/RTX, n = 8), seven patients were given WBE without IVIG/RTX (group 2, WBE alone, n = 7), and seven patients who failed initial IVIG/RTX therapy were given sequential WBE therapy (group 3 IVIG/RTX→WBE, n = 7). Fourteen patients had accepted WBE treatment regardless of prior IVIG/RTX usage (group 2 + 3, WBE ± IVIG/RTX, n = 14). On days 1, 3, 5, and 7 after corresponding therapies, patients of groups 2, 3, and 2 + 3 showed significantly higher levels of haemoglobin (Hb) than patients of group 1. Compared with patients of group 1, patients of groups 2, 3, and 2 + 3 took less time to reach and maintain Hb ≥60 g/L from baseline. Groups 2 and 2 + 3 consumed a lower dose of GCs than group 1 to reach and maintain Hb ≥60 g/L from baseline. Group 1 experienced longer hospital stays than group 2, and group 3’s cost of hospitalisation is more than groups 1 and 2. Hbmin

With the development of manufacturing industry, more and more torque tools are used in various industrial fields, such as torque wrench, torque multiplier, hydraulic torque wrench, electric torque wrench, various torque sensors, etc. The calibration of these tools is related to the quality of manufacturing products. National institute of metrology of China has established several torque standard devices and carried out calibration of various torque tools. This paper introduces the related work.

Abstract Despite the broad potential applications of C-glycosides, facile synthetic methods remain scarce. Transforming glycosyltransferases with promiscuous or natural O-specific chemoselectivity to C-glycosyltransferases is challenging. Here, we employ rational directed evolution of the glycosyltransferase MiCGT to generate MiCGT-QDP and MiCGT-ATD mutants which either enhance C-glycosylation or switch to O-glycosylation, respectively. Structural analysis and computational simulations reveal that substrate binding mode govern C-/O-glycosylation selectivity. Notably, directed evolution and mechanism analysis pinpoint the crucial residues dictating the binding mode, enabling the rational design of four enzymes with superior non-inherent chemoselectivity, despite limited sequence homology. Moreover, our best mutants undergo testing with 34 substrates, demonstrating superb chemoselectivities, regioselectivities, and activities. Remarkably, three C-glycosides and an O-glycoside are produced on a gram scale, demonstrating practical utility. This work establishes a highly selective platform for diverse glycosides, and offers a practical strategy for creating various types of glycosylation platforms to access pharmaceutically and medicinally interesting products.

Abstract Background Nonalcoholic steatohepatitis (NASH) is a prevalent chronic liver condition. However, the potential therapeutic benefits and underlying mechanism of nicotinate-curcumin (NC) in the treatment of NASH remain uncertain. Methods A rat model of NASH induced by a high-fat and high-fructose diet was treated with nicotinate-curcumin (NC, 20, 40 mg·kg− 1), curcumin (Cur, 40 mg·kg− 1) and metformin (Met, 50 mg·kg− 1) for a duration of 4 weeks. The interaction between NASH, Cur and Aldo-Keto reductase family 1 member B10 (AKR1B10) was filter and analyzed using network pharmacology. The interaction of Cur, NC and AKR1B10 was analyzed using molecular docking techniques, and the binding energy of Cur and NC with AKR1B10 was compared. HepG2 cells were induced by Ox-LDL (25 µg·ml− 1, 24 h) in high glucose medium. NC (20µM, 40µM), Cur (40µM) Met (150µM) and epalrestat (Epa, 75µM) were administered individually. The activities of ALT, AST, ALP and the levels of LDL, HDL, TG, TC and FFA in serum were quantified using a chemiluminescence assay. Based on the changes in the above indicators, score according to NAS standards. The activities of Acetyl-CoA and Malonyl-CoA were measured using an ELISA assay. And the expression and cellular localization of AKR1B10 and Acetyl-CoA carboxylase (ACCα) in HepG2 cells were detected by Western blotting and immunofluorescence. Results The results of the animal experiments demonstrated that NASH rat model induced by a high-fat and high-fructose diet exhibited pronounced dysfunction in liver function and lipid metabolism. Additionally, there was a significant increase in serum levels of FFA and TG, as well as elevated expression of AKR1B10 and ACCα, and heightened activity of Acetyl-CoA and Malonyl-CoA in liver tissue. The administration of NC showed to enhance liver function in rats with NASH, leading to reductions in ALT, AST and ALP levels, and decrease in blood lipid and significant inhibition of FFA and TG synthesis in the liver. Network pharmacological analysis identified AKR1B10 and ACCα as potential targets for NASH treatment. Molecular docking studies revealed that both Cur and NC are capable of binding to AKR1B10, with NC exhibiting a stronger binding energy to AKR1B10. Western blot analysis demonstrated an upregulation in the expression of AKR1B10 and ACCα in the liver tissue of NASH rats, accompanied by elevated Acetyl-CoA and Malonyl-CoA activity, and increased levels of FFA and TG. The results of the HepG2 cell experiments induced by Ox-LDL suggest that NC significantly inhibited the expression and co-localization of AKR1B10 and ACCα, while also reduced levels of TC and LDL-C and increased level of HDL-C. These effects are accompanied by a decrease in the activities of ACCα and Malonyl-CoA, and levels of FFA and TG. Furthermore, the impact of NC appears to be more pronounced compared to Cur. Conclusion NC could effectively treat NASH and improve liver function and lipid metabolism disorder. The mechanism of NC is related to the inhibition of AKR1B10/ACCα pathway and FFA/TG synthesis of liver.

Abstract DNA methylation at the fifth position of cytosine (5-methylcytosine, 5mC) is a crucial epigenetic modification for regulating gene expression, but little is known about how it regulates gene expression in insects. Here, we pursue the detailed molecular mechanism by which DNMT1-mediated 5mC maintenance regulates female reproduction in the German cockroach, Blattella germanica. Our results show that Dnmt1 knockdown decreases the level of 5mC in the ovary, upregulating numerous genes during choriogenesis, especially the transcription factor ftz-f1. The hypomethylation at the ftz-f1 promoter region increases and prolongs ftz-f1 expression in ovarian follicle cells during choriogenesis, which consequently causes aberrantly high levels of 20-hydroxyecdysone and excessively upregulates the extracellular matrix remodeling gene Mmp1. These changes further impair choriogenesis and disrupt fertilization by causing anoikis of the follicle cells, a shortage of chorion proteins, and malformation of the sponge-like bodies. This study significantly advances our understanding of how DNA 5mC modification regulates female reproduction in insects.

Summary: Molecular mechanisms underlying quantitative variations of pathogenicity remain elusive. Here, we identified the Xanthomonas campestris XopJ6 effector that triggers disease resistance in cauliflower and Arabidopsis thaliana. XopJ6 is a close homolog of the Ralstonia pseudosolanacearum PopP2 YopJ family acetyltransferase. XopJ6 is recognized by the RRS1-R/RPS4 NLR pair that integrates a WRKY decoy domain mimicking effector targets. We identified a XopJ6 natural variant carrying a single residue substitution in XopJ6 WRKY-binding site that disrupts interaction with WRKY proteins. This mutation allows XopJ6 to evade immune perception while retaining some XopJ6 virulence functions. Interestingly, xopJ6 resides in a Tn3-family transposon likely contributing to xopJ6 copy number variation (CNV). Using synthetic biology, we demonstrate that xopJ6 CNV tunes pathogen virulence on Arabidopsis through gene dosage-mediated modulation of xopJ6 expression. Together, our findings highlight how sequence and structural genetic variations restricted at a particular effector gene contribute to bacterial host adaptation.

Abstract Tea is known for having a high catechin content, with the main component being (−)-epigallocatechin gallate (EGCG), which has significant bioactivities, including potential anti-cancer and anti-inflammatory activity. The poor intestinal stability and permeability of EGCG, however, undermine these health-improving benefits. O-methylated EGCG derivatives, found in a few tea cultivars in low levels, have attracted considerable interest due to their increased bioavailability. Here, we identify two O-methyltransferases from tea plant: CsFAOMT1 that has a specific O-methyltransferase activity on the 3ʹʹ-position of EGCG to generate EGCG3′′Me, and CsFAOMT2 that predominantly catalyzes the formation of EGCG4″Me. In different tea tissues and germplasms, the transcript levels of CsFAOMT1 and CsFAOMT2 are strongly correlated with the amounts of EGCG3ʹʹMe and EGCG4ʹʹMe, respectively. Furthermore, the crystal structures of CsFAOMT1 and CsFAOMT2 reveal the key residues necessary for 3ʹʹ- and 4ʹʹ-O-methylation. These findings may provide guidance for the future development of tea cultivars with high O-methylated catechin content.

The effects of different preheating treatments on the microstructure and mechanical properties of extruded Mg–13Gd–4Y–2Zn–0.5Zr (wt.%) alloys were investigated by using high-throughput experiments in this paper. The results showed that the solid solution and aging prior to extrusion (SAE) samples with heterogeneous microstructure had the best strength-plasticity synergy with ultimate tensile strength (UTS), yield strength (TYS) and elongation (EL) reaching 446.35 ± 3.1 MPa, 382.5 ± 2.5 MPa and 6.5 ± 0.8%, respectively. The formation of heterogeneous microstructures was mainly attributed to the weakening of the particle stimulation nucleation (PSN) effect by the dissolution of the primary Mg5RE phase during the solid solution process and the strong Zener pinning effect of the dynamic Mg5RE phase precipitation during the extrusion process, which inhibited grain boundary migration and grain growth. Optimum strength-plasticity synergy was due to fine grain strengthening, second phase strengthening, texture strengthening and heterogeneous deformation induced (HDI) strengthening. Strain gradients between deformed grains and dynamic recrystallized (DRXed) grains were generated during deformation process, in order to coordinate the deformation and generate more geometrically necessary dislocations (GNDs) within the deformed grains, resulting in a strong HDI effect. The increase in plasticity was mainly attributed to the change in texture type due to the rotation of the lattice, which promoted the activation of non-basal slip systems. This study provided an efficient and rapid method for probing optimal heat treatment parameters, aiming to reduce the influence of uncontrollable factors on experimental results and increase the rigor of the experiment.

Inflammatory bowel disease （IBD） is a group of chronic nonspecific intestinal inflammatory diseases with unknown etiology. It has been found that approximately 10%-20% of IBD occurs in old age. At present， the prevalence and quantity of elderly-onset IBD are increasing. The treatment strategy of elderly-onset IBD becomes complicated by physical function， presence of comorbidities and multi-drug interactions， which simultaneously affect the selection of IBD-related drugs. In this article， literature search at home and abroad was conducted from 2017 to 2023， aiming to illustrate the characteristics of elderly-onset IBD from two aspects of treatment and malignant tumor surveillance， and provide reference for clinical practice.

Phthalate acid ester hydrolases are of promise for the microbial degradation of phthalate acid ester plasticizers, however, only a small number of PAE hydrolases have been characterized. Here, the authors report the structural and functional characterization of MehpH, a monoalkyl phthalate (MBP) hydrolase that degrades MBP to phthalic acid and butanol.

Antimicrobial toxins are secreted by bacteria to kill rival species. Here the authors report the mechanism of inhibition of EsaD, a toxin secreted by some S. aureus strains to kill competitors that lack the antitoxin EsaG, showing marked mechanistic differences to other Type II toxin-antitoxin systems.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the gradual loss of midbrain dopaminergic neurons in association with aggregation of α-synuclein. Oxidative damage has been widely implicated in this disease, though the mechanisms involved remain elusive. Here, we demonstrated that preferential accumulation of peroxidized phospholipids and loss of the antioxidant enzyme glutathione peroxidase 4 (GPX4) were responsible for vulnerability of midbrain dopaminergic neurons and progressive motor dysfunctions in a mouse model of PD. We also established a mechanism wherein iron-induced dopamine oxidation modified GPX4, thereby rendering it amenable to degradation via the ubiquitin-proteasome pathway. In conclusion, this study unraveled what we believe to be a novel pathway for dopaminergic neuron degeneration during PD pathogenesis, driven by dopamine-induced loss of antioxidant GPX4 activity.

The Yersinia outer protein J (YopJ) family of effectors, which are present in many plant and animal pathogens are non-canonical acetyltransferases that are activated by the eukaryote-specific cofactor inositol hexaphosphate (InsP6). Here, the authors combine X-ray crystallography, biochemical and functional analyses to characterise the structure and activation mechanism of the YopJ family effector PopP2 from the plant pathogen Ralstonia solanacearum and observe that InsP6 binding induces major conformational changes in PopP2 with a helix-to-strand fold-switching in its catalytic core.

The continued warming of the Arctic atmosphere and ocean has led to a record retreat of sea ice in the last decades. This retreat has increased the probability of the opening of the Arctic Passages in the near future. The Northwest Passage (NWP) is the most direct shipping route between the Atlantic and Pacific Oceans, producing notable economic benefits. Decadal variations of sea ice and its influencing factors from a high-resolution unstructured-grid finite-volume community ocean model were investigated along the NWP in 1988–2016, and the accessibility of the NWP was assessed under shared socioeconomic pathways (SSP245 and 585) and two vessel classes with the Arctic transportation accessibility model in 2021–2050. Sea ice thickness has decreased with increasing seawater temperature and salinity, especially within the Canadian Arctic Archipelago (CAA) in 1988–2016, which has facilitated the opening of the NWP. Complete ship navigation is projected to be possible for polar class 6 ships in August–December in 2021–2025, after when it may extends to July under SSP585 in 2026–2030, while open water ships will not be able to pass through the NWP until September in mid-21st century. The navigability of the NWP is mainly affected by the ice within the CAA. For the accessibility of the Parry Channel, the west part is worse than that of the eastern part, especially in the Viscount-Melville Sound.

Background Hypoxia is considered a major leading cause of pulmonary hypertension (PH). In this study, the roles and molecular mechanism of circ_0016070 in PH were studied. Methods and Results The expression of circ_0016070 in serum samples, human pulmonary artery smooth muscle cells and hypoxia/monocrotaline‐treated rats was determined by real‐time quantitative polymerase chain reaction. Cell viability, migration, and apoptosis were analyzed by Cell Counting Kit‐8, wound healing, flow cytometry, and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays, respectively. The molecular interactions were validated using RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase reporter assays. The levels of phenotype switch‐related proteins were evaluated by Western blot and immunohistochemistry. The pathological characteristics were assessed using hematoxylin and eosin staining. circ_0016070 was highly expressed in the serum samples, hypoxia‐induced pulmonary artery smooth muscle cells and pulmonary arterial tissues of PH rats. Downregulation of circ_0016070 ameliorated the excessive proliferation, migration, vascular remodeling, and phenotypic transformation but enhanced cell apoptosis in the PH rat model. In addition, micro (miR)‐340‐5p was verified as a direct target of circ_0016070 and negatively regulated TCF4 (transcription factor 4) expression. TCF4 formed a transcriptional complex with β‐catenin to activate TWIST1 (Twist family bHLH transcription factor 1) expression. Functional rescue experiments showed that neither miR‐340‐5p inhibition nor TWIST1 or TCF4 upregulation significantly impeded the biological roles of circ_0010670 silencing in PH. Conclusions These results uncovered a novel mechanism by which circ_0016070 play as a competing endogenouse RNA of miR‐340‐5p to aggravate PH progression by promoting TCF4/β‐catenin/TWIST1 complex, which may provide potential therapeutic targets for PH.

Abstract Background The idiosyncratic hepatotoxicity of Polygonum multiflorum (PM) has attracted considerable interest, but the idiosyncratically hepatotoxic components and endogenous metabolite changes resulting from idiosyncratic hepatotoxicity of PM are not well understood. The aim of this study was to identify the idiosyncratically hepatotoxic components and potential endogenous metabolic biomarkers for PM-induced liver injury. Methods Serum biochemical indicators and hematoxylin and eosin (H&E) staining were evaluated to identify pathological changes. Gas chromatography/mass spectrometry (GC-MS) was performed to identify changes in metabolic biomarkers. Orthogonal projection to latent structures discriminant analysis (OPLS-DA) was applied to determine group clustering trends and differential metabolites. Results The results for the liver index, the liver function index and liver pathology showed that Polygonum multiflorum ethanol extract (PME), 50% ethanol elution fractions and tetrahydroxystilbene glucoside (TSG) from PME can induce idiosyncratic hepatotoxicity. TSG was the main idiosyncratically hepatotoxic component. Forty endogenous metabolites were identified in the rat liver. Six biomarkers, including lower levels of L-valine and higher levels of 3-hydroxybutyric acid, hexadecanoic acid, ribose, phosphoric acid and oxalic acid, were related to PM-induced liver injury. These differential biomarkers led to disruptions in amino acid, fatty acid, oxalate, energy and glucose metabolism. A total of 32 types of endogenous metabolites were identified in rat serum. Ten biomarkers were related to the liver injury induced by TSG, including lower levels of L-valine and L-proline and higher levels of urea, caproic acid, DL-malic acid, D-mannose, 3-hydroxybutyric acid, D-galactose, octadecane and hexadecanoic acid. These differential biomarkers led to disruptions in amino acid, glucose and fat metabolism. The mechanism of idiosyncratic hepatotoxicity in PM involves TSG-induced disruptions in amino acid metabolism, lipid metabolism, energy metabolism and glucose metabolism. Conclusions These findings reflect the material basis and metabolic mechanism of idiosyncratic PM hepatotoxicity.

Artificial intelligence (AI), especially the rapid development of deep learning, has a profound impact on various industries and has continuously changed the traditional production methods and lifestyles. From passive learning with computing power to autonomous learning and enhanced learning, the development of machine intelligence is largely due to the innovation of the AI theory and practice. AI has also had a far-reaching impact on the military field, as it has provided modern warfare with new features such as intelligence, interconnectedness, and destructiveness. Winning in a military confrontation requires not only machine intelligence but also human wisdom. Therefore, human-machine collaboration would combine the strengths and complement the weaknesses of human and machine, which is the key to victory in the increasingly complex war environment. How to achieve a high degree of hybrid human–artificial intelligence to obtain a good result of “1+1>2” is also a problem that needs to be further explored in military confrontation. This paper reviewed the application of AI in military confrontation as the starting point and highlighted the important measures and achievements of representative countries in the use of AI technology in the military development process. Moreover, we analyzed the development status from the two perspectives of confrontation strategy and the three-tier architecture of the Internet of Things, revealed the shortcomings of using AI in the current military field, and analyzed the development trend of hybrid human–artificial intelligence in military confrontation. We also presented three possible technical schemes and detailed explanations and finally proposed future research directions. We believe that the future development trend of intelligent military may be based on the hybrid human–artificial intelligence, which will further improve the adaptability of machines to the combat environment and reveal the merits of the integration of human wisdom and machine intelligence; this integration may be the next step of AI research in military confrontation.

Abstract Background The flowers and dried fruit spikes of Prunella vulgaris L. (P. vulgaris L.) have been widely used in traditional Chinese medicine and food. P. vulgaris L. is regarded as a good option for treating uterine myoma (UM). However, scientific evidence of anti-UM activity of the extract of P. vulgaris L. (PVE) is lacking. The present study aimed to characterize the chemical composition of PVE and evaluate the pharmacodynamics and mechanism of PVE against UM. Methods The chemical composition of PVE was analyzed by GC-MS. MTT was used to screen and evaluate cell proliferation and toxicity. Double fluorescence flow cytometry method were used to determine the apoptosis and cell cycle progression of UM cells under PVE treatment. The anti-UM activity of PVE was investigated by using a specific-pathogen-free (SPF) rat model of UM. TUNEL staining was used to detect the apoptosis of UM cells. The concentrations of estrogen and progesterone in the serum of SPF rats were detected by ELISA. The expression levels of PCNA, estrogen receptor alpha, estrogen receptor beta, progesterone receptor, survivin, caspase-3, Bax and Bcl-2 in the uterus of SPF rats was detected by immunohistochemistry (IHC). Results The extraction rate of PVE was 8.1%. The main components were squalene (28.3%), linoleic acid (9.96%), linolenic acid (9.95%), stearic acid (6.26%) and oleic acid (5.51%). In vitro, PVE had significant anti-human UM cell activity, exhibited no drug toxicity, promoted the apoptosis of human UM cells, and inhibited the transition of UM cells from the G0/G1 stage into the G2 stage, in which DNA replication occurs. In vivo, PVE had significant anti-UM activity. PVE decreased the concentrations of estrogen and progesterone and downregulated the expression levels of the estrogen and progesterone receptors through the estrogen signaling pathway. PVE also promoted the apoptosis of UM cells by downregulating the expression levels of the survivin and Bcl-2 proteins and upregulating the expression levels of caspase-3 and Bax through the mitochondria-mediated apoptotic pathway. Conclusion PVE has marked anti-UM activity. PVE can be used as an ideal candidate drug to treat UM.

Context Acute myocardial infarction (AMI) is defined as myocardial necrosis. Clinicians use the traditional Chinese patent medicine Yangxinkang Tablet (YXK) to treat chronic heart failure. Objective To explore the effects of YXK on heart injury following AMI and the underlying mechanisms. Materials and methods The AMI model was produced in Wistar rats by permanent ligation of the left anterior descending coronary artery. Rats were divided into the following five groups: Sham (n = 6), MI (Model, n = 10), AICAR (AMPK agonist, 50 mg/kg/d, i.p., n = 10), Compound C (AMPK inhibitor, 10 mg/kg/d, i.p., n = 10), and YXK (0.72 g/kg/d, gavage, n = 10) groups. Cardiac function, cardiac fibrosis, apoptosis, and expression of p-AMPK, p-mTOR, and autophagy-related proteins was measured after 4 weeks of treatment after the successful modelling of the AMI. Results Compared to MI group, both YXK and AMPK inhibitor improved cardiac dysfunction and reduced cardiac fibrosis (15.6 ± 2.3; 22.6 ± 4.6 vs. 34.6 ± 4.3%) and myocardial cell apoptosis (12 ± 3.67; 25.6 ± 6.8 vs. 54 ± 4.8%). Futhermore, YXK and AMPK inhibitor significantly decreased p-AMPK expression by 11.05% and 14.64%, LC3II/I by 25.08% and 35.28% and Beclin-1 by 66.71% and 33.85%, increased p-mTOR by 22.14% and 47.46% and p62 by 70.83% and 18.58%. Conclusions The underlying mechanism appears to include suppression of autophagy via inhibiting AMPK/mTOR signalling, suggesting that YXK may serve as a potentially effective Chinese herbal compound for suppressing cardiac fibrosis in heart injury.

In this paper, a hot processing map that takes into the strengthening effect into account is optimized for the Al–10.0Zn–3.0Mg–2.8Cu alloy, mainly considering the crushing and dissolving behavior of the insoluble phase. The hot deformation experiments were performed by compression testing with strain rates ranging from 0.001 to 1 s−1 and the temperature ranging from 380 to 460 °C. The hot processing map was established at the strain of 0.9. It exhibits that the appropriate hot processing region is located at the temperature from 431 to 456 °C and its strain rate is within 0.004–0.108 s−1. The recrystallization mechanisms and insoluble phase evolution were demonstrated using the real-time EBSD-EDS detection technology for this alloy. It is verified that the work hardening can also be consumed by the coarse insoluble phase refinement with the strain rate increasing from 0.001 to 0.1 s−1, besides the traditional recovery and recrystallization, but the effect of the insoluble phase crushing was weakened when strain rate increased over 0.1 s−1. Better refinement of the insoluble phase was around strain rate in 0.1 s−1, which exhibits adequate dissolving during the solid solution treatment, leading to excellent aging strengthen effects. Finally, the hot processing region was further optimized, so that the strain rate approaches 0.1 s−1 instead of 0.004–0.108 s−1. This will provide a theoretical support for the subsequent deformation of the Al–10.0Zn–3.0Mg–2.8Cu alloy and its’ engineering application in aerospace, defense and military fields.

This paper employs empirical data in three major Asian real estate markets - Hong Kong, Japan, and Singapore, from 2001 to 2021, to study the leverage strategies of two related types of real estate companies – real estate investment trusts (REITs) and real estate operating companies (REOCs). The business model of the former must adhere to a real-estate-focused investment strategy while the latter undertakes a whole range of real estate development activities including land acquisition, financial feasibility analysis, construction, investment and asset management to redevelopment and disposal, and are not subject to the REIT rules with respect to tax transparency, earning distribution, real estate holding and leverage limit. We find that REOCs use 18.96% more debt than REITs after controlling for the agency and market risks, dividend yields, and property sector, country, and year fixed effects of firms; dividend payout has no effect on the leverage strategies; and high tax ratio increases the debt usage of REOCs relative to REITs. We also analyze the liquidation costs and business uniqueness effects. We find real estate value to total firm value ratio, as a proxy of liquidation cost, has negative effects on debt ratios for both real estate firms. Due to their uniqueness, REOCs with a high concentration of rental revenue stream are more vulnerable to liquidation risks, and thus more likely to have lower debt ratio. REITs however tend to have higher debt usage as rental incomes enhance cash-flow liquidity. [ABSTRACT FROM AUTHOR]

ABSTRACT: Objective Hedyotis corymbosa (Shui Xian Cao, 水线草, HC) is the main antitumor medicine in China and other southeast Asian countries. A comprehensive quality control system of HC was established in this study, as the current system was ineffective.Methods Microscopy was used to observe the characteristics of the powder and cross-sectional tissue. Thin layer chromatography (TLC) was employed to separate HC from Hedyotis diffusa (Bai Hua She She Cao, 白花蛇舌草, HD). Simultaneously, high-performance liquid chromatography (HPLC) was used to establish the characteristic spectrum of HC and determine the concentrations of hedyotiscone A. Regarding the issue of systematicness, concentrations of water, total ash, acid-insoluble ash, heavy metals (including lead, arsenic, mercury, cadmium and copper) and pesticide residue were measured by the methods described in the 2015 edition of Chinese Pharmacopoeia.Results Calcium oxalate needle crystal bundles and oil drops were observed in the cross-sectional tissue. Three characteristic blue fluorescent spots were observed in the HC samples by TLC. There were five distinct characteristic peaks in HC but not in HD, and hedyotiscone A was the sharpest characteristic peak. The generated linear equation of hedyotiscone A was Y = 3.15 × 108X + 312.04 (r2 = 1.000) between 0.00005270 and 0.002108 mg/mL, and the average recovery was 100.42%. Precision [relative standard deviation (RSD) 0.92%], repeatability (RSD 0.14%), and recovery (RSD 0.85%) met the requirements for quantitative analysis. Hedyotiscone A concentrations ranged from 0.00017%∼0.00113% across different habitats. Concentrations of water, ash and acid-insoluble ash were 8.80%∼11.2%, 7.00%∼15.3% and 0.440%∼7.70%, respectively. Concentrations of Pb, As, Hg, Cd and Cu were 1.60∼4.60, 0.650∼1.60, 0.0300∼0.100, 0.240∼0.690 and 10.1∼16.6 µg/g, respectively. Pesticide residues were less than 0.00100 ppm.Conclusion The quality control system can effectively distinguish HC from HD, so as to comprehensively control the quality of HC, to provide references for the clinical use of HC. Keywords: Hedyotis corymbosa, Hedyotis diffusa, Hedyotiscone A, TLC, HPLC, Quality standard

Background: Childhood leukemia is one of the most common cancers in children. As a potential treatment for leukemia, immunotherapy has become a new research hotspot. This research aimed at exploring the status and trends of current researches on immunotherapy for childhood leukemia through bibliometric analysis.Methods: The Institute for Scientific Information Web of Science core collection database was searched for articles on immunotherapy and childhood leukemia using a computer. Time period for retrieval was from the beginning of the database to June 15, 2019. The top 100 highly cited articles were selected to extract their information on publication year, authors, title, publication journal, number of citations, author’s affiliations, country, and so on. These general information and bibliometric data were collected for analysis. VOSviewer software was used to generate a figure for keywords’ co-occurrence network and a figure for researcher’s coauthorship network that visualized reference and cooperation patterns for different terms in the 100 articles.Results: The number of citations in the top 100 articles ranged from 17 to 471. These articles were published in 52 different publications. The top four journals in terms of the number of our selected articles were Leukemia (11 articles), Blood (10 articles), Bone Marrow Transplantation (6 articles), and Clinical Cancer Research. The most frequently nominated author was T. Klingebiel from Goethe University Frankfurt, and of the top 100 articles, 12 listed his name. These top 100 articles were published after the year 2000. Most of these articles were original (67%). The United States and Germany were the major countries researching immunotherapy for childhood leukemia and made significant contributions to the combat against the disease. Adoptive immunotherapy and stem cell transplantation appeared more frequently in keywords.Conclusions: This study analyzed the top 100 highly cited articles on immunotherapy for childhood leukemia and provided insights into the features and research hotspots of the articles on this issue.

A simple experimental equipment and test scheme is designed to estimate the swelling deformation under the lateral unconfined condition with coupling effect of uniaxial load and water-rock interaction. This paper carried out the swelling test under the lateral unconfined condition and analyzed the qualities of lateral unconfined swelling of weak swelling rock by applying simple self-designed saturated equipment to the swelling test on the platform of microcomputer-controlled rock shear rheological tester RYL-600. As a result of this study, the following conclusions were derived: (1) considering the coupling effect of load and water, the stress level is considerably lower than the mudstone-saturated uniaxial compressive strength, and it is discovered that the coupling effect is striking. (2) The swelling reveals the demonstrable time effect, which increases rapidly at the beginning of the swelling deformation, and after that, the deformation tends to maintain a certain value. (3) Both the rate and the scale of swelling deformation are restrained by the axial load.

A new electronic system to realize time reversal (TR) of electromagnetic waves is proposed in this paper. By utilizing the dispersion compensation approach, the system mainly contains a chirped pulse generator, a wideband multiplier, and a chirped delay line (CDL). The TR transformation is achieved by dispersing the modulated chirped pulse through a single microwave CDL. The chirped electromagnetic band gap structure with a reflected group delay slope is fabricated and used to be the CDL. It has been demonstrated by experiments that TR of triangular-wave signals in the microwave regime can be obtained through the proposed system.