[Clinical trials and evaluation of Chinese patent medicine for influenza].

The clinical randomized controlled trial(RCT) of Chinese patent medicine in the treatment of influenza were reviewed and analyzed to provide basic information for clinical decision and related research. On the basis of the collection in the Traditional Chinese Medicine(TCM) Clinical Evidence Database System(EVDS), CNKI, Wanfang, VIP, SinoMed, EMbase, PubMed, and Cochrane Library were searched for RCTs of Chinese patent medicine for influenza published from database inception to July 25, 2021. The publication time, sample size, intervention and control measures, course of treatment, outcome indicators, and methodological quality of the trials were analyzed and evaluated. Ninety-two RCTs of Chinese patent medicine for influenza published between 2005 and 2021, were included, among which 17 RCTs(18.48%) had a sample size higher than 200 and the average sample size was about 145. Twenty-seven Chinese patent medicines were involved, including twenty-one oral medicines and six injections. The Chinese patent medicines in trials reported in more than five papers included Lianhua Qingwen Capsules/Gra-nules, Tanreqing Injection, and Reduning Injection. Fourteen intervention protocols were reported, of which Chinese patent medicine+western medicine+conventional treatment vs western medicine+conventional treatment(20.65%) was the most frequently employed. Additionally, 85.87% of the RCTs reported the course of treatment, and 80.43% of the RCTs determined 3-7 d as the intervention course. Forty-five outcome indicators were extracted, which were used 434 times, including symptoms/signs, physicochemical detection, safety events, TCM symptoms/syndromes, quality of life, long-term prognosis, and economic evaluation. Symptoms/signs(61.52%) exhibited the highest frequency. Methodological problems were prevalent in the included trials. The findings reveal that there are few clinical trials on influenza treatment by Chinese patent medicine, and the methodological problems are prominent, affec-ting the reliability and practicability of the trials. In the future research, the value characteristics of Chinese patent medicine should be highlighted and the quality control in the whole process should be strengthened based on the scientific and rigorous design.

[Analysis of outcome indexes in randomized controlled trials of traditional Chinese medicine for rheumatic heart disease].

The present study analyzed the efficacy evaluation indexes of the randomized controlled trials(RCTs) of Chinese medi-cine in the treatment of rheumatic heart disease to lay the foundation for the construction of the corresponding core outcome index set. Clinical RCTs with a definite diagnosis of rheumatic heart disease were retrieved from CNKI, Wanfang, VIP, Sino Med, Pub Med, EMbase, and Cochrane Library from January 1, 2010, to December 31, 2020. Thirty-five RCTs were included, involving 3 314 patients and 41 efficacy evaluation indexes, which covered seven domains [traditional Chinese medicine(TCM) symptoms/syndromes, symp-toms/signs, physical and chemical examination, quality of life, long-term prognosis, economic evaluation, and safety events]. Physi-cal and chemical examination(56. 91%) and symptoms/signs(29. 27%) were the more frequently applied. The number of indexes used in a single trial ranged from 1 to 15, with an average of 4. The measurement time points of the top five indexes in the frequency of use were as follows: total response rate was reported at five measurement time points, ranging from 14 days to 6 months; left ventri-cular ejection fraction was measured at eight time points ranging from 5 days to 6 months; left ventricular end systolic diameter was measured at six time points, ranging from 5 days to 6 months; interleukin-2(IL-2) and tumor necrosis factor-α(TNF-α) were repor-ted 28 days after treatment. At present, there are many problems in the efficacy outcome indexes of RCTs in the treatment of rheumatic heart disease with TCM, such as large difference in quantity, unclear primary and secondary indexes, unreasonable selection of " surro-gate indexes", insufficient attention to long-term prognostic indexes and safety event indexes, non-standard application of composite in-dexes, long measurement period, and lack of TCM characteristics. It is urgent to establish the core outcome set for TCM treatment of rheumatic heart disease.

Study on the relationship between SLCO1B1 and ApoE gene polymorphisms and the risk of coronary heart disease in the Mongolian population.

Objective This study aimed to analyze the influence of SLCO1B1 and APOE gene polymorphisms on coronary heart disease in Mongolian population who living in Ordos area. Methods From January 2019 to June 2020, 200 Mongolian patients with coronary heart disease admitted to our hospital and other banner hospitals were selected as the case group. At the same time, 150 randomly selected healthy Mongolian people from medical examination centers comprised the control group. The polymorphisms of SLCO1B1 (388A>G, 521 T > C) and ApoE (388 T > C, 526 C > t) were detected by real-time polymerase chain reaction. Combined with environmental data, the effect of gene polymorphism on coronary heart disease was explored. Results Both SLCO1B1 and ApoE polymorphisms satisfied Hardy-Weinberg equilibrium. The SLCO1B1 genotype *1a/*1b showed the highest frequency in the case group, accounting for 35.0%, while The SLCO1B1 genotype *1b/*1b showed the highest frequency in the control group, accounting for 32.0%. Allele *1b was the most commonly seen allele in both the case group and control group (57.8% and 53.7%, respectively). Meanwhile, The difference in the distribution of SLCO1B1 *1a/*15 genotype between the two groups was statistically significant (P < .05). Conclusion The results showed that the SLCO1B *1a/*15 genotype, ApoE ε3 /ε3 genotype, and ε3 allele reduced the risk of coronary disease in the Mongolian population, making them protective genes against this disease, while the ApoE ε4 allele increased the risk of coronary disease, making it a coronary disease risk factor.

Coherent Control of Nitrogen-Vacancy Center Spins in Silicon Carbide at Room Temperature.

Solid-state color centers with manipulatable spin qubits and telecom-ranged fluorescence are ideal platforms for quantum communications and distributed quantum computations. In this work, we coherently control the nitrogen-vacancy (NV) center spins in silicon carbide at room temperature, in which telecom-wavelength emission is detected. We increase the NV concentration sixfold through optimization of implantation conditions. Hence, coherent control of NV center spins is achieved at room temperature, and the coherence time T_{2} can be reached to around 17.1 µs. Furthermore, an investigation of fluorescence properties of single NV centers shows that they are room-temperature photostable single-photon sources at telecom range. Taking advantage of technologically mature materials, the experiment demonstrates that the NV centers in silicon carbide are promising platforms for large-scale integrated quantum photonics and long-distance quantum networks.

Genomic identification and characterization of MYC family genes in wheat (Triticum aestivum L.).

BACKGROUND: MYC transcriptional factors are members of the bHLH (basic helix-loop-helix) superfamily, and play important roles in plant growth and development. Recent studies have revealed that some MYCs are involved in the crosstalk between Jasmonic acid regulatory pathway and light signaling in Arabidopsis, but such kinds of studies are rare in wheat, especially in photo-thermo-sensitive genic male sterile (PTGMS) wheat line. RESULTS: 27 non-redundant MYC gene copies, which belonged to 11 TaMYC genes, were identified in the whole genome of wheat (Chinese Spring). These gene copies were distributed on 13 different chromosomes, respectively. Based on the results of phylogenetic analysis, 27 TaMYC gene copies were clustered into group I, group III, and group IV. The identified TaMYC genes copies contained different numbers of light, stress, and hormone-responsive regulatory elements in their 1500 base pair promoter regions. Besides, we found that TaMYC3 was expressed highly in stem, TaMYC5 and TaMYC9 were expressed specially in glume, and the rest of TaMYC genes were expressed in all tissues (root, stem, leaf, pistil, stamen, and glume) of the PTGMS line BS366. Moreover, we found that TaMYC3, TaMYC7, TaMYC9, and TaMYC10 were highly sensitive to methyl jasmonate (MeJA), and other TaMYC genes responded at different levels. Furthermore, we confirmed the expression profiles of TaMYC family members under different light quality and plant hormone stimuli, and abiotic stresses. Finally, we predicted the wheat microRNAs that could interact with TaMYC family members, and built up a network to show their integrative relationships. CONCLUSIONS: This study analyzed the size and composition of the MYC gene family in wheat, and investigated stress-responsive and light quality induced expression profiles of each TaMYC gene in the PTGMS wheat line BS366. In conclusion, we obtained lots of important information of TaMYC family, and the results of this study was supposed to contribute novel insights and gene and microRNA resources for wheat breeding, especially for the improvement of PTGMS wheat lines.

Polyacrylonitrile-Derived Sponge-Like Micro/Macroporous Carbon for Selective CO2 Separation.

CO2 capture under a dynamical flow situation requires adsorbents possessing balanced proportion of macropores as diffusion path and micropores as adsorption reservoir. However, the construction of interconnected micro-/macropores structure coupled with abundant nitrogen species into one carbon skeleton remains a challenge. Here, we report a new approach to prepare sponge-like carbon with a well-developed micro-/macroporous structure and enriched nitrogen species through aqueous phase polymerization of acrylonitrile in the presence of graphene oxide. The tension stress caused by the uniform thermal shrinkage of polyacrylonitrile during the pyrolysis together with the favorable flexibility of graphene oxide sheets are responsible for the formation of the sponge-like morphology. The synergistic effect of micro-/macroporous framework and rich CO2 -philic site enables such carbon to decrease resistance to mass transfer and show high CO2 dynamic selectivity over N2 (454) and CH4 (11), as well as good CO2 capacity at 298 K under low CO2 partial pressure (0.17 bar, a typical CO2 partial pressure in flue gas). The above attributes make this porous carbon a promising candidate for CO2 capture from flue gas, methane sources and other relevant applications.

Morphological and molecular divergence of Rhipicephalus turanicus tick from Albania and China.

Rhipicephalus turanicus is an important tick species potentially carrying tick-borne pathogens. Several tick species have obvious subspecies divergence. However few studies aimed to examine the existence of divergence within R. turanicus. Therefore, a detailed morphological and molecular analysis was conducted for comparing R. turanicus from the Mediterranean Basin (represented by Albania) and Central Asia (Northwestern China). Altogether 315 adult ticks of R. turanicus (103 from Albania and 212 from China) were morphologically and molecularly analysed. DNA samples were used for mitochondrial 16S rRNA and cox1 gene sequences analysis. In addition, as potentially genetic markers, three fragments including partial nad1-16S rRNA, nad2-cox1, cox1-tRNA-Lys, were designed and then phylogenetically analyzed. Based on detailed morphological observations, only basis capituli length:width ratio (females), the length, the width and the length:width ratio of the scutum (males) had differences between R. turanicus from China and Albania. Gene divergences of 16S rRNA, cox1, partial nad1-16S rRNA, nad2-cox1 and cox1-tRNA-Lys from China and Albania ticks were 3.53-4.84, 3.57-4.92, 3.57-4.07, 3.57-4.39 and 3.18-4.69%, respectively. The evaluated five genetic markers revealed two phylogenetic branches in R. turanicus. Obvious differences exist within R. turanicus based on morphological and genetic analysis. Three newly designed genetic markers (partial nad1-16S rRNA, nad2-cox1 and cox1-tRNA-Lys) in this study may be suitable genetic tools for identification and analysis in R. turanicus. Subspecies analysis of R. turanicus from other regions of the world should be initiated in the future.

[Huoxiang Zhengqi formulas for treatment of gastrointestinal type cold：a systematic review and Meta-analysis].

This systematic review aims to evaluate the efficacy and safety of Huoxiang Zhengqi formulas in treating gastrointestinal type cold. Seven electronic databases,including CNKI, WanFang Data, Vip, SinoMed, PubMed, Cochrane Library, Embase will be searched from the inception of the study until March 2017.All randomized controlled trials that evaluate the treatment of Huoxiang Zhengqi formulas for gastrointestinal type cold will be eligible. The methodological quality will be assessed using the Cochrane risk of bias tool for randomized clinical trials and Review Manager 5.3 software is used for analyzing the data.The results are： eight RCTs and 680 patients are included .Meta-analysis are performed according to the stratification of the treatment strategy. Eight studies report clinical efficacy, among them four studies show Huoxiang Zhengqi formulas are better than western medicine(RR and 95%,1.2[1.08, 1.33]), another four studies showHuoxiang Zhengqi formulas in conjunction with conventional treatment are better than conventional treatment(RR and 95%, 1.32[1.20,1.46]).About symptom remission rate, one study shows the treatment group effect is better than the control group from the following clinical symptoms：chills,fever,bowel diarrhea,the effect of treating sore throat itchy is same with western medicine treatment.No adverse reactions are found about Huoxiang Zhengqi formulas in this study.Current evidence shows that Huoxiangzhengqi formulas are better than Western medicine group and western medicine routine treatment group from clinical efficacy. Limited by the quantity and quality of studies, more large-scale and rigorously designed randomised controlled trials with large sample size are warranted to clarify the conclusions.

Ultrastable Polymolybdate-Based Metal-Organic Frameworks as Highly Active Electrocatalysts for Hydrogen Generation from Water.

Two novel polyoxometalate (POM)-based metal-organic frameworks (MOFs), [TBA]3[ε-PMo(V)8Mo(VI)4O36(OH)4Zn4][BTB]4/3·xGuest (NENU-500, BTB = benzene tribenzoate, TBA(+) = tetrabutylammonium ion) and [TBA]3[ε-PMo(V)8Mo(VI)4O37(OH)3Zn4][BPT] (NENU-501, BPT = [1,1'-biphenyl]-3,4',5-tricarboxylate), were isolated. In these compounds, the POM fragments serving as nodes were directly connected with organic ligands giving rise to three-dimensional (3D) open frameworks. The two anionic frameworks were balanced by TBA(+) ions residing inside the open channels. They exhibit not only good stability in air but also tolerance to acidic and basic media. Furthermore, they were employed as electrocatalysts for the hydrogen evolution reaction (HER) owing to the combination of the redox activity of a POM unit and the porosity of a MOF. Meanwhile, the HER activities of ε(trim)(4/3), NENU-5, and HKUST-1 were also studied for comparison. Remarkably, as a 3D hydrogen-evolving cathode operating in acidic electrolytes, NENU-500 exhibits the highest activity among all MOF materials. It shows an onset overpotential of 180 mV and a Tafel slope of 96 mV·dec(-1), and the catalytic current density can approach 10 mA·cm(-2) at an overpotential of 237 mV. Moreover, NENU-500 and NENU-501 maintain their electrocatalytic activities after 2000 cycles.

Protective effects of Arctium lappa L. roots against hydrogen peroxide-induced cell injury and potential mechanisms in SH-SY5Y cells.

Accumulated evidence has shown that excessive reactive oxygen species (ROS) have been implicated in neuronal cell death related with various chronic neurodegenerative disorders. This study was designed to explore neuroprotective effects of ethyl acetate extract of Arctium lappa L. roots (EAL) on hydrogen peroxide (H2O2)-induced cell injury in human SH-SY5Y neuroblastoma cells. The cell viability was significantly decreased after exposure to 200 µM H2O2, whereas pretreatment with different concentrations of EAL attenuated the H2O2-induced cytotoxicity. Hoechst 33342 staining indicated that EAL reversed nuclear condensation in H2O2-treated cells. Meanwhile, TUNEL assay with DAPI staining showed that EAL attenuated apoptosis was induced by H2O2. Pretreatment with EAL also markedly elevated activities of antioxidant enzyme (GSH-Px and SOD), reduced lipid peroxidation (MDA) production, prevented ROS formation, and the decrease of mitochondrial membrane potential. In addition, EAL showed strong radical scavenging ability in 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) assays. Furthermore, EAL inhibited H2O2-induced apoptosis by increases in the Bcl-2/Bax ratio, decreases in cytochrome c release, and attenuation of caspase-3, caspase-9 activities, and expressions. These findings suggest that EAL may be regarded as a potential antioxidant agent and possess potent neuroprotective activity against H2O2-induced injury.

Prostatic arterial embolization for the treatment of lower urinary tract symptoms due to large (>80 mL) benign prostatic hyperplasia: results of midterm follow-up from Chinese population.

BACKGROUND: Currently, large prostate size (>80 mL) of benign prostatic hyperplasia (BPH) still pose technical challenges for surgical treatment. This prospective study was designed to explore the safety and efficacy of prostatic arterial embolization (PAE) as an alternative treatment for patients with lower urinary tract symptoms (LUTS) due to largeBPH. METHODS: A total of 117 patients with prostates >80 mL were included in the study; all were failure of medical treatment and unsuited for surgery. PAE was performed using combination of 50-µm and 100-µm particles in size, under local anaesthesia by a unilateral femoral approach. Clinical follow-up was performed using the international prostate symptoms score (IPSS), quality of life (QoL), peak urinary flow (Qmax), post-void residual volume (PVR), international index of erectile function short form (IIEF-5), prostatic specific antigen (PSA) and prostatic volume (PV) measured by magnetic resonance (MR) imaging, at 1, 3, 6 and every 6 months thereafter. RESULTS: The prostatic artery origins in this study population were different from previously published results. PAE was technically successful in 109 of 117 patients (93.2%). Follow-up data were available for the 105 patients with a mean follow-up of 24 months. The clinical improvements in IPSS, QoL, Qmax, PVR, and PV at 1, 3, 6, 12, and 24 months was 94.3%, 94.3%, 93.3%, 92.6%, and 91.7%, respectively. The mean IPSS (pre-PAE vs post-PAE 26.0 vs 9.0; P < .0.01), the mean QoL (5.0 vs 3.0; P < 0.01), the mean Qmax (8.5 vs 14.5; P < 0.01), the mean PVR (125.0 vs 40.0; P < 0.01), and PV (118.0 vs 69.0, with a mean reduction of 41.5%; P < 0.01 ) at 24-month after PAE were significantly different with respect to baseline. The mean IIEF-5 was not statistically different from baseline. No major complications were noted. CONCLUSIONS: PAE is a safe and effective treatment method for patients with LUTS due to large volume BPH. PAE may play an important role in patients in whom medical therapy has failed, who are not candidates for open surgery or TURP or refuse any surgical treatment.

[Systematic economic assessment and quality evaluation for traditional Chinese medicines].

To learn about the economic studies on traditional Chinese medicines in domestic literatures, in order to analyze the current economic assessment of traditional Chinese medicines and explore the existing problems. Efforts were made to search CNKI, VIP, Wanfang database and CBM by computer and include all literatures about economic assessment of traditional Chinese medicines published on professional domestic journals in the systematic assessment and quality evaluation. Finally, 50 articles were included in the study, and the systematic assessment and quality evaluation were made for them in terms of titles, year, authors' identity, expense source, disease type, study perspective, study design type, study target, study target source, time limit, cost calculation, effect indicator, analytical technique and sensitivity analysis. The finally quality score was 0.74, which is very low. The results of the study showed insufficient studies on economics of traditional Chinese medicines, short study duration and simple evaluation methods, which will be solved through unremitting efforts in the future.

[Simultaneous Determination of Five Astragalosides in Astragali Radix and Jinqi Jiangtang Tablet by HPLC-ELSD].

OBJECTIVE: To develop an HPLC-ELSD method for simultaneous determination of Astragaloside IV Astragaloside I, Astragaloside II, Astragaloside III and Isostragaloside II in Astragali Radix and Jinqi Jiangtang tablet. METHODS: The chromatographic conditions were as follows: Grace Apollo C18 column (250 mm x 4. 6 mm, 5 µm), acetonitrile (A) and water(B) as mobile phases for gradient elution, and the flow rate being 1. 0 mL/min. RESULTS: Five components showed good linearity. The average recoveries were between 95% - 105%. Five Astragalosides were determined in twelve batches of Astragali Radix and ten batches of Jinqi Jiangtang tablet. CONCLUSION: This is a specific, sensitive and simple method for simultaneous determination of Astragaloside IV, Astragaloside I Astragaloside II, Astragaloside III and Isostragaloside II in Astragali Radix and Jinqi Jiangtang tablet.

Macrophage inhibitory factor 1 acts as a potential biomarker in patients with esophageal squamous cell carcinoma and is a target for antibody-based therapy.

Macrophage inhibitory factor 1 (MIC1) is frequently altered in various cancers. The aim of this study was to investigate the clinical significance of MIC1 for esophageal squamous cell carcinoma (ESCC). Serum MIC1 of 286 ESCC and 250 healthy subjects was detected, the diagnostic performance was assessed and compared with SCC, CEA, CA199 and CA724, and the value as a prognostic indicator was also evaluated. The expression of MIC1 in ESCC cell lines, tissues were detected, and the inhibition of MIC1 antibody on ESCC was carried out in vitro and in vivo. The results showed that the serum MIC1 of ESCC was significantly higher than normal groups (P < 0.001), and was positively associated with tumor invasion (P = 0.030) as well as lymph node metastasis (P = 0.007). The sensitivity of MIC1 was significantly better than SCC, CEA, CA199 and CA724, especially for stage I ESCC. Patients with higher serum MIC1 also had a poorer prognosis in relapse-free (P = 0.050) and tumor-specific survival (P = 0.005). In vitro studies showed that the expression of MIC1 was upregulated in 37.5% (3/8) ESCC cell lines and 45% (18/40) tissues, and the transcription of MIC1 in tumor tissues was significantly higher than paired adjacent normal tissues (P = 0.001). The antibody of MIC1 inhibited the tumor growth (P < 0.001), and showing preference for tumor tissues in xenograft model. The decreased formation of neovascularization lumen may be involved in the mechanism. We conclude that MIC1 plays an important role in the progression of ESCC and can serve as a potential biomarker and therapeutic target for ESCC.

Generation and characterization of a new mammalian cell line continuously expressing virus-like particles of Japanese encephalitis virus for a subunit vaccine candidate.

BACKGROUND: Japanese encephalitis virus (JEV) is the most important cause of epidemic encephalitis in most Asian regions. There is no specific treatment available for Japanese encephalitis, and vaccination is the only effective way to prevent JEV infection in humans and domestic animals. The purpose of this study is to establish a new mammalian cell line stably and efficiently expressing virus-like particle of JEV for potential use of JEV subunit vaccine. RESULTS: We generated a new cell clone (BJ-ME cells) that stably produces a secreted form of Japanese encephalitis virus (JEV) virus-like particle (VLP). The BJ-ME cells were engineered by transfecting BHK-21 cells with a code-optimized cDNA encoding JEV prM and E protein expression plasmid. Cell line BJ-ME can stably produces a secreted form of Japanese encephalitis virus virus-like particle (JEV-VLP) which contains the JEV envelope glycoprotein (E) and membrane protein (M). The amount of JEV-VLP antigen released into the culture fluid of BJ-ME cells was as high as 15-20 µg/ml. JEV-VLP production was stable after multiple cell passages and 100% cell expression was maintained without detectable cell fusion or apoptosis. Cell culture fluid containing the JEV-VLP antigen could be harvested five to seven times continuously at intervals of 4-6 days while maintaining the culture. Mice immunized with the JEV-VLP antigen with or without adjuvant developed high titers of neutralizing antibodies and 100% protection against lethal JEV challenge. CONCLUSION: These results suggest that the recombinant JEV-VLP antigen produced by the BJ-ME cell line is an effective, safe and affordable subunit Japanese encephalitis vaccine candidate, especially for domestic animals such as pig and horse.

Role of Th2, Th17 and Treg Cells and relevant cytokines in pathogenesis of allergic rhinitis.

OBJECTIVE: To explore the role of different cells and molecules in the pathogenesis of allergic rhinitis (AR) with positive Artemisia allergen by detecting their expression levels. METHODS: From January 2021 to December 2022,200 AR patients diagnosed in the Otolaryngology Clinic of Ordos Central Hospital were selected as the AR group, and 50 healthy people who underwent physical examination in the hospital during the same period were randomly selected as the healthy control (HC) group. The levels of GATA-3mRNA, RORγtmRNA and FoxP3mRNA in peripheral blood mononuclear cells were detected by real-time fluorescence quantitative PCR (qRT-PCR). The proportions of Th2, Th17 and Treg cells were detected by flow cytometry. The concentrations of IL-4, IL-5, IL-17 and IL-10 in serum were detected by enzyme-linked immunosorbent assay. The differences of transcription gene level, immune cell ratio and cytokine concentration between the two groups were analyzed. RESULTS: There was no difference in age and gender between the two groups. The levels of GATA-3mRNA and RORγtmRNA transcription genes in peripheral blood mononuclear cells, the percentage of Th2, Th17 and Treg immune cells, the levels of eosinophils and basophils in peripheral blood, the concentrations of IL-4, IL-5, IL-17, IL-10 cytokines and IgE in serum of AR patients were significantly higher than those in HC group (P < 0.05). IL-4 and IL-17 were positively correlated with total IgE level. CONCLUSION: The secretion of immune cells and cytokines in peripheral blood of AR patients is abnormal. Th2, Th17, Treg specific transcription factors and related cells and cytokines are involved in the occurrence and development of allergic rhinitis.

Repair of dysfunctional bone marrow endothelial cells alleviates aplastic anemia.

Aplastic anemia (AA) is a life-threatening disease characterized by bone marrow (BM) failure and pancytopenia. As an important component of the BM microenvironment, endothelial cells (ECs) play a crucial role in supporting hematopoiesis and regulating immunity. However, whether impaired BM ECs are involved in the occurrence of AA and whether repairing BM ECs could improve hematopoiesis and immune status in AA remain unknown. In this study, a classical AA mouse model and VE-cadherin blocking antibody that could antagonize the function of ECs were used to validate the role of BM ECs in the occurrence of AA. N-acetyl-L-cysteine (NAC, a reactive oxygen species scavenger) or exogenous EC infusion was administered to AA mice. Furthermore, the frequency and functions of BM ECs from AA patients and healthy donors were evaluated. BM ECs from AA patients were treated with NAC in vitro, and then the functions of BM ECs were evaluated. We found that BM ECs were significantly decreased and damaged in AA mice. Hematopoietic failure and immune imbalance became more severe when the function of BM ECs was antagonized, whereas NAC or EC infusion improved hematopoietic and immunological status by repairing BM ECs in AA mice. Consistently, BM ECs in AA patients were decreased and dysfunctional. Furthermore, dysfunctional BM ECs in AA patients led to their impaired ability to support hematopoiesis and dysregulate T cell differentiation toward proinflammatory phenotypes, which could be repaired by NAC in vitro. The reactive oxygen species pathway was activated, and hematopoiesis- and immune-related signaling pathways were enriched in BM ECs of AA patients. In conclusion, our data indicate that dysfunctional BM ECs with impaired hematopoiesis-supporting and immunomodulatory abilities are involved in the occurrence of AA, suggesting that repairing dysfunctional BM ECs may be a potential therapeutic approach for AA patients.

Addition of Chelators Increased the Stability of Black Rice Anthocyanins against the Metallic Ions in Tap Water and Improved the Coloration of Steamed Cold Noodles.

The anthocyanins in black rice extract (BRA) are sensitive to metallic ions, which restrict its application in the coloration of steamed cold noodles in China that uses tap water as the solvent. Food-grade chelators were added to check if they could increase the stability of BRA. The results indicated that the color decay of BRA in tap water was mainly caused by Fe3+, Cu2+, and Fe2+, and the addition of chelators could effectively antagonize this effect. Coloration with the BRA solution containing the optimized chelator formulation of 0.01% ethylenediaminetetraacetic acid disodium, 0.08% sodium hexametaphosphate, and 0.064% sodium tartrate conferred comparable appearance and chromatic attributes with those of the noodle colored by deionized water-dissolved BRA. The steamed cold noodles colored by the chelators-containing BRA exhibited increased springiness and decreased starch retrogradation, and possessed potential health functions due to its slightly increased resistant starch content and markedly enhanced antioxidant capacity. Hence, the addition of chelators is a feasible way to increase the color stability of BRA in tap water, and the chelators-supplemented BRA could be used to produce steamed cold noodles with attractive color and health benefits.

Fabrication of lipase-loaded particles by coacervation with chitosan.

Coacervation of the lipase from Aspergillus oryzae (AOL) with chitosan was a feasible way to fabricate lipase-loaded particles and the optimum conditions were phase separation pH 5.5, chitosan to AOL mass ratio 1:5, and temperature 25 °C in the absence of NaCl, which conferred an AOL loading efficiency of up to 95.48% and activity recovery of 69.60%. The AOL-chitosan coacervates were highly porous and more susceptible to weight loss upon heating. Coacervation with chitosan increased the activity of AOL and shifted its optimum pH from 7.0 to 6.0, but exerted no effect on its optimum temperature (45 °C). Thermal deactivation kinetics analysis revealed that the coacervated AOL was more thermal stable, while the Michaelis-Menten kinetics analysis indicated that coacervation with chitosan increased the Vmax of AOL by 2.4 folds, but decreased its substrate affinity by 3.6 folds. Hence, the AOL-chitosan coacervates are potential in the construction of Pickering emulsion-based lipase catalysis systems.

Population pharmacokinetic analysis for dabigatran etexilate in Chinese patients with non-valvular atrial fibrillation.

We aimed to develop a pharmacokinetic (PK) and pharmacodynamic (PD) model from healthy Chinese subjects and real-world non-valvular atrial fibrillation (NVAF) patients. We also investigated meaningful intrinsic and extrinsic factors and related biomarkers for bleeding events. We characterized the integrated PK/PD models based on rich PK/PD data [dabigatran concentration, activated partial thromboplastin time (APTT), prothrombin time (PT), and anti-factor IIa (anti-FIIa) activity] from 118 healthy volunteers and sparse PD data [APTT, PT, and anti-FIIa] from 167 patients with NVAF after verifying the model extrapolation performance. We also documented the correlations between PD biomarkers and clinically relevant bleeding events over one year. Next, we used the final integrated PK/PD model (a two-compartment, linear model with first-order absorption) to evaluate the influence of dosage and individual covariates on PD parameters. The age, high-density liptein cholesterol (HDL-C), and creatinine clearance (CrCL) improved the PK model fit. The linear direct-effects PD model described the correlation between APTT, PT, and anti-FIIa and plasma concentration. CrCL improved the PD model fit. Anti-FIIa was more sensitive to the increase in dabigatran exposure than APTT and PT in the PD model. Therefore, fixed dabigatran doses could be prescribed for patients with NVAF without adjusting for age and HDL-C. We observed an elevated bleeding tendency with higher peak and trough values of APTT, PT, and anti-FIIa. Randomized studies should be performed to evaluate the efficacy and safety of low-dose dabigatran in Chinese patients with NVAF.