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Temperature is an important factor affecting the changes in the amount of gas exchanged between eggs and the surrounding during storage. The effect of temperature changes on the release of carbon dioxide (CO2) from eggs was studied using eggs from the same breed. The experimental samples were divided into three groups, and placed in a storage box at 4, 25, or 35°C with 65% relative humidity for 20 days, and a breathalyser was used to measure the amount of CO2 released by the eggs. The FLUENT software was used to simulate the diffusion at different temperatures. The conclusion from the present work was that as the temperature decreased, the amount and speed of CO2 released by the eggs also decreased. The simulation results show that the diffusion of CO2 released by egg respiration can be divided into the following sequential stages: initial, descending, mixing, and turbulence. When the storage temperature was 4°C, the CO2 cloud of eggs was the lowest, followed by 35°C, and finally 25°C. The results show that the direction of gas diffusion was mainly affected by temperature, diffusion volume, and diffusion velocity, and that temperature mainly affected vertical gas diffusion. The present work thus provides a theoretical basis for egg respiration related research.

Animal medicine is a large category of Chinese medicinecommonly used in clinical practice and has important scientific and therapeutic value. Animal medicine isscarcer than herbal medicine. In recent years, with the vigorous development of traditional Chinese medicine(TCM),the contradiction between the increasing industrial demand andsupply of scarce and even endangered medicinal animals has become increasingly prominent. The continuous lack of medicinal animal resources affects the clinical demandandalso causes serious damage to the ecological environment. Only relying on artificial breeding is not enough to alleviate the current condition of depletion. In the face of this dilemma, it is a major challenge for the current industrial development to protect animal resources and meet clinical and industrial needs withquot;available medicinesquot;. The application of substitutes for animal medicines isthe key focus to alleviate this problem, and it is also the key scientific issue to be solved urgently in the modernization of TCM. This paper summarizedand reviewedthe history, current situation, strategies, and methods of animal medicinesubstitution and put forward the point of view ofquot;similar chemical characteristics, similar efficacy, and higher safetyquot; to provide references for scientific substitution and resource protection of rare animals.

Natural product bufotenine (5) which could be isolated from Venenum Bufonis, has been widely used as a tool in central nervous system (CNS) studies. We present here its quaternary ammonium salt (6) which was synthesized with high yields using 5-benzyloxyindole as raw materials, and we firstly discover its analgesic effects in vivo. The analgesic evaluation showed that compounds 5 and 6 had stronger effects on the behavior of formalin induced pain in mice. Moreover, the combination of compound 6 and morphine has a synergistic effect. We intended to explain the molecular mechanism of this effect. Therefore, 36 analgesic-related targets (including 15 G protein-coupled receptors, 6 enzymes, 13 ion channels, and 2 others) were systemically evaluated using reverse docking. The results indicate that bufotenine and its derivatives are closely related to acetyl cholinesterase (AChE) or α4β2 nicotinic acetylcholine receptor (nAChR). This study provides practitioners a new insight of analgesic effects.

To observe the effect of moxibustion on the regulation of nuclear factor-kappa B (NF-κB) and inflammatory factors by multiple microRNAs (miRNAs) in rats with diarrhea-predominant irritable bowel syndrome (IBS-D), and to explore the anti-inflammatory mechanism of moxibustion on IBS-D.Twelve of 52 newborn rats were randomly selected into a normal group. The remaining rats were made into IBS-D model. A total of 36 rats with successful model were randomly divided into a model group, a medication group and a moxibustion group, 12 rats in each group. The rats in the medication group were intraperitoneally injected with pyrrolidine dithiocarbamate (PDTC). The rats in the moxibustion group were treated with moxibustion at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) for 20 min each time. All the intervention was given once a day for 7 days. Before and after modeling as well as after intervention, the body mass, loose stool rate and the minimum volume threshold of abdominal withdrawal reflex (AWR) were measured. After intervention, the contents of serum tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-8 were detected by ELISA method; the morphology of colon tissues was observed by HE staining, and the expressions of miR-155, miR-125b, miR-29b, miR-31, miR-18a and NF-κB p65 mRNA in colon tissues were detected by real-time PCR. The expressions of NF-κB p65, TNF-α, IL-1β and IL-8 protein in colon tissues were detected by immunofluorescence.After modeling, the body mass and the minimum volume threshold of AWR in the model group were lower than those in the normal group (The anti-inflammatory mechanism of moxibustion at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) for IBS-D rats may be related to regulating multiple miRNAs to inhibit NF-κB signal pathway and reduce the expression of inflammatory factors.

Sulfur-driven autotrophic denitrification (SDAD), a process suited for the treatment of nitrogen and sulfur-polluted wastewater without extra supplement of organic carbon, is a promising biological nitrogen removal process. However, the SDAD process was affected by many factors such as various electron donors, organic carbon and exogenous substances (e.g., antibiotics and heavy metal), which prevent further application. Thus, we conducted a detailed review of previous studies on such influence factors and its current application. Besides, a comparative analysis was adopted to recognize the current challenges and future needs for feasible application, so as to ultimately perfect the SDAD process and extend its application scope.

Hepatic fibrosis is characterized by hepatic stellate cell (HSC) activation and transdifferentiation-mediated extracellular matrix (ECM) deposition, which both contribute to cirrhosis. However, no antifibrotic regimen is available in the clinic. microRNA-23b/27b/24-1 cluster inhibition of transforming growth factor-β (TGF-β) signaling during hepatic development prompted us to explore whether this cluster inhibits HSC activation and hepatic fibrosis.Experimental fibrosis was studied in carbon tetrachloride (CClIn this study, we showed that increasing the miR-23b/27b/24-1 level through intravenous delivery of miR-23b/27b/24-1 lentivirus ameliorated mouse hepatic fibrosis. Mechanistically, the miR-23b/27b/24-1 cluster directly targeted messenger RNAs, which reduced the protein expression of 5 secretory profibrotic genes (TGF-β2, Gremlin1, LOX, Itgα2, and Itgα5) in HSCs. Suppression of the TGF-β signaling pathway by down-regulation of TGF-β2, Itgα2, and Itgα5, and activation of the bone morphogenetic protein signaling pathway by inhibition of Gremlin1, decreased extracellular matrix secretion of HSCs. Furthermore, down-regulation of LOX expression softened the ECM. Moreover, a reduction in tissue inhibitors of metalloproteinase 1 expression owing to weakened TGF-β signaling increased ECM degradation.Hepatic overexpression of the miR-23b/27b/24-1 cluster blocked hepatic fibrosis and may be a novel therapeutic regimen for patients with hepatic fibrosis.

E proteins are transcriptional regulators that regulate many developmental processes in animals and lymphocytosis and leukemia in Homo sapiens. In particular, E2A, a member of the E protein family, plays a major role in the transcriptional regulatory network that promotes the differentiation and development of B and T lymphocytes. E2A-mediated transcriptional regulation usually requires the formation of E2A dimers, which then bind to coregulators. In this review, we summarize the mechanisms by which E2A participates in transcriptional regulation from a structural perspective. More specifically, the C-terminal helix-loop-helix (HLH) region of the basic HLH (bHLH) domain first dimerizes, and then the activation domains of E2A bind to different coactivators or corepressors in different cell contexts, resulting in histone acetylation or deacetylation, respectively. Then, the N-terminal basic region (b) of the bHLH domain binds to or dissociates from a specific DNA motif (E-box sequence). Last, trans-activation or trans-repression occurs. We also summarize the properties of these E2A domains and their interactions with the domains of other proteins. The feasibility of developing drugs based on these domains is discussed.

Aim: This study aimed to develop anthracycline-loaded bacterial magnetosomes (BMs) with enhanced anticancer efficiency and elucidate their endocytosis mechanism. Methods: Drug-loaded BMs (DBMs) were successfully prepared and characterized. DBMs endocytosis was investigated within HepG2 cells. The anticancer effect of DBMs was studied both in vitro and in vivo. Results: Doxorubicin–BMs and daunorubicin–BMs showed enhanced growth inhibitory effect in vitro and in vivo with no notable toxicity to normal tissues. The DBMs were internalized into cells through caveolae-mediated endocytosis and macropinocytosis. The loaded drugs were released from DBMs in cytoplasm and entered the nucleus to exert their activity. Conclusion: Our findings offer promising candidates for improved cancer therapy with a clear mechanism of DBMs endocytosis and working principle.

Objective: To explore the efficacy of implantable collamer lense (ICL) combined with laser keratectomy via corneal epithelium Trans-PRK in the treatment of patients with high myopia and its effect on corneal endothelial cell density. Methods: A prospective analysis was performed on patients with ultra-high myopia admitted to the department of ophthalmology of our hospital from March 2014 to March 2017. Six months after ICL implantation, the patients still had myopia and received Trans PRK treatment again. The number of cases was 30 and 52 eyes. Patients were followed up postoperatively. Uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA), dioptre (D), intraocular pressure, ICL arch height, anterior chamber volume, anterior chamber depth, and changes in corneal endothelial cell counts were observed preoperatively, 6 months after ICL implantation and 6 months after Trans PRK so as to assess the effectiveness and safety of the surgery. Results: UCVA and BCVA of the eyes were significantly higher 6 months after ICL implantation and 6 months after Trans-PRK than those before the surgery, and UCVA of the eyes 6 months after Trans-PRK was significantly higher than that 6 months after ICL implantation. There was no increase in intraocular pressure in all patients after surgery. There was no significant difference in intraocular pressure preoperatively, 6 months after ICL implantation and 6 months after Trans PRK. The ICL arch height of the eyes 6 months after Trans-PRK was slightly lower than that 6 months after ICL implantation, but the difference was not statistically significant. Both anterior chamber volume and anterior chamber depth were significantly lower 6 months after ICL implantation and 6 months after Trans PRK than whose before the surgery, and anterior chamber depth 6 months after Trans PRK was significantly lower than that 6 months after ICL implantation. The number of corneal endothelial cells 6 months after ICL implantation was slightly less than that before surgery, but it was not statistically significant. The number of corneal endothelial cells 6 months after Trans PRK was higher than that 6 months after ICL implantation and close to the preoperative level. Conclusion: Trans PRK can effectively improve the eye diopter of patients with high myopia and residual myopia after ICL implantation. It has little effect on the density of corneal endothelial cells, can significantly improve visual acuity, and achieve the expected operation effect with safe operation, which is worthy of clinical promotion.

As 'chemical antibodies', aptamers have some advantages, such as lack of immunogenicity, rapid tissue penetration, cell internalization and so on. Consequently, more and more aptamers have been screened out by the systematic evolution of ligands through exponential enrichment for the desired cells or membrane receptors. On the basis of the result, researchers use aptamers to guide drug targeting to the desired cells and internalization in vivo.In this review, we explore the mechanisms of cargo- or aptamer-mediated internalization, and then briefly summarize five strategies for exploring the mechanism of aptamer internalization. Finally, we focus on four types of applications involving aptamer internalization: aptamers as drugs, aptamers as chemical drug-delivery systems, aptamer-based chimeras and aptamer-conjugated nanoparticles or block copolymer micelles.Two aptamer-internalization mechanisms are known, namely receptor-mediated endocytosis and macropinocytosis. The latter mechanism, which is has only been verified in the internalization of nucleolin aptamer shuttles between the nucleus and cytoplasm, may be important for nuclear internalization and cargo molecule escape from the endosomal compartment. Thus, it is feasible to use some strategies to further explore the macropinocytosis internalization mechanism and then to screen for aptamers similar to the nucleolin aptamer for use with the desired cell types as a targeted delivery tool.

Background: High mobility group box 1 (HMGB1), an important “late” inflammatory mediator, is a therapeutic target for bacterial sepsis. Ethyl pyruvate (EP) has anti-inflammatory effects, and prevents bacterial sepsis by decreasing HMGB1 levels. However, the role of HMGB1 in fungal sepsis is still unclear. Therefore, we investigated HMGB1 mRNA and protein levels in serum and tissue from patients and mice with invasive C. albicans infection. We explored the anti-HMGB1 effects of EP, which may be of benefit in the diagnosis and treatment of invasive C. albicans infections. Methods: We measured serum HMGB1 mRNA and protein levels in four different patient groups: 23 control subjects (group 1), 35 patients with sepsis without fungal infection (group 2), 35 patients with severe sepsis without fungal infection (group 3), and 23 patients with severe sepsis with C. albicans infection (group 4). We collected clinical indices to estimate correlations between HMGB1 levels and disease severity. Furthermore, we experimentally stimulated mice with C. albicans and C. albicans + EP, and examined HMGB1 mRNA and protein levels from serum and tissue. We determined liver and kidney functions, investigated pathological changes in tissues and assessed mortality. We also investigated serum levels of the proinflammatory cytokines, tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in these animals. Results: Serum HMGB1 mRNA and protein levels in patients with severe sepsis with C. albicans infection were elevated. Increased HMGB1 levels were correlated with procalcitonin (PCT), C-reactive protein (CRP), 1,3-β-D-Glucan (BDG) and C. albicans sepsis severity. HMGB1 mRNA and protein levels in serum and tissues were significantly increased within seven days after mice were infected with C. albicans. The administration of EP inhibited HMGB1 levels, decreased tissue damage, increased survival rates and inhibited the release of TNF-α and IL-6.Conclusions: Increased HMGB1 levels in patients with severe sepsis with C. albicans infection were positively correlated with PCT, CRP, BDG, and disease severity. EP prevented C. albicans lethality by decreasing HMGB1 expression and release. We suggest that HMGB1 plays a vital role in invasive C. albicans infections and may provide an effective diagnostic and therapeutic target for such infections in clinical settings.

The coronavirus disease 2019 (COVID-19) is an epidemic disease caused by the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) and spreading throughout the world rapidly. Here we evaluated the efficacy of the Lopinavir/Ritonavir (LPV/r) and its combination with other drugs in the treatment of COVID-19. We included 170 confirmed COVID-19 patients who had been cured and discharged. Their antiviral therapies were LPV/r alone or combinations with interferon (IFN), Novaferon and Arbidol. We evaluated the medication efficacy by comparing the time of the negative nucleic acid conversion and the length of hospitalization mainly. The LPV/r + Novaferon [6.00 (4.00-8.00) and 7.50 (5.00-10.00) days] had shorter time of the negative nucleic acid conversion (P = .0036) and shorter time of hospitalization (P

Purpose: Carbapenem-resistant organisms (CROs) pose great challenges for clinical treatment. Polymyxin B (PMB) is one of the “last resort” choices of CRO infections. We explored the possible factors affecting PMB efficacy. Methods: This retrospective study involved CRO infected patients treated with PMB for ≥72 h. The endpoint indicator was clinical efficacy. We compared the characteristics (demographics, pathogenic bacteria, PMB treatment) between patients who had “clinical success” (CS) and “clinical failure” (CF).Results: A total of 192 patients were enrolled: 110 in the CS group and 82 in the CF group. The total cumulative dose for the CS group was higher than the CF group [1100 (700–1443.75) vs. 800 (500–1112.5) mg; P = 0.001]. Treatment duration in the CS group was longer than the CF group [11 (8–14) vs. 8 (6–11) days; P < 0.000]. Multivariate logistic regression analysis showed mechanical ventilation, vasoactive agents, multiple-site infection, and total cumulative dose to be independently associated with clinical efficacy. Cox survival analysis for 30-day mortality also showed that the use of vasoactive agents and the total cumulative dose of PMB could influence survival time and mortality rate independently.Conclusion: PMB had good efficacy and a low prevalence of adverse reactions. The total cumulative dose，duration of PMB treatment, mechanical ventilation, vasoactive agents, and multiple-site infection were factors associated with the clinical efficacy of PMB.

Background: The coronavirus disease 2019 (COVID-19) is threatening the lives and health of people all over the world since its outbreak in Wuhan, Hubei province, China. Up to now, thousands of clinical trials have been registered, but there are still no effective and specific drugs for COVID-19 treatment. Large randomized controlled clinical trials face many challenges and the quality of COVID-19 clinical trials is also worrying. Methods: We searched all the COVID-19 clinical trials registered on the Chinese Clinical Trials Registry and ClinicalTrials.gov on June 29, 2020. Then we extracted the basic information of these COVID-19 clinical trials and analyzed the current dilemma of clinical trials of COVID-19. Results: A total of 3021 studies were retrieved, including 665 trials from the Chinese Clinical Trial Registry and 2356 trials from ClinicalTrials.gov. Among these clinical trials, 293 and 1314 intervention studies were registered in the Chinese Clinical Trial Registry and ClinicalTrials.gov, respectively. Up to now, only 4.48% of these intervention trials have completed their recruitment, and there were still 11.60% of studies registered in the Chinese Clinical Trials Registry have not yet been approved by the ethics committee. Phase II and phase III studies that could prove the safety and effectiveness of drugs accounted for 42.25%. The median and interquartile range (IQR) of sample size was 100 (60, 200) and 384 (50, 120) in the Chinese Clinical Trial Registry and ClinicalTrials.gov, respectively. The number of randomized controlled trials (RCTs) were rare, and 50.71% of these studies were open-label. Conclusions: The quality of COVID-19 clinical trials that have been registered was low, and no reliable results have been published due to the design deficiency. Well-designed and cooperative trials are urgently needed to defeat the COVID-19 epidemic.

The effectiveness of acupuncture in the treatment of dry eye has been confirmed, but the association between acupoint selection and therapeutic effect has remained to be elucidated. In the present study, a systematic review and meta-analysis were performed to evaluate the effect of periocular acupoints and periocular acupoints plus body acupoints compared with AT for the treatment of dry eye disease (DED). The PubMed, Cochrane Library, Embase, Ovid, China National Knowledge Infrastructure and Chonqing VIP Information, Co., Ltd. databases were searched with entries until 10 July 2018 considered. Only randomized controlled trials (RCTs) were included. Meta-analyses were performed to compare the effects of acupuncture with those of conventional treatment (including AT or other non-acupuncture therapies). The primary outcomes, including tear break-up time (BUT), Schirmer's I test (SIT) result and Symptom scores were analyzed. Subgroup analysis was performed for periocular acupoints only and periocular acupoints plus body acupoints. A total of 12 studies comprising 900 participants were included. In the primary meta-analysis, a significant improvement in the BUT [n=1,209, weighted mean difference (WMD)=1.01, 95% CI: 0.56-1.84, P

Fruit ripening is a progress involving many physiological changes regulated by various plant hormones such as indole-3-acetic acid (IAA) and salicylic acid (SA). The levels of these hormones in fruit with the spatial-temporal resolution can provide detailed information for the study and evaluation of the fruit ripening. Herein paper-based analytical devices and the microsampling technique were coupled for the analysis of IAA and SA in different locations of the tomato fruit during ripening. Because of its excellent electric conductivity, the ITO glass was used as the substrate of the disposable working electrodes and modified with conductive carbon cement. The ITO modified electrodes in the paper-based analytical devices were utilized for analysis of IAA and SA in tiny tomato samples obtained with the technique of microsampling. Our results showed that the amounts of IAA and SA in the locular tissue of tomato fruit decreased via time in the process of ripening. More importantly, the spatial profiling of IAA and SA in immature and mature tomatoes could be directly differentiated at the molecular level. This study suggested that low-cost paper-based electroanalytical devices could become an effective platform for rapid evaluation of the fruit ripening.

Sulfur-driven autotrophic denitrification (SDAD) is feasible for the treatment of low-C/N-ratio and sulfur-laden wastewaters. The nitrite accumulated in SDAD will affect the performance and stability of the system but can be a potential electron acceptor. Thus, single- and multiple-electron acceptor-mediated SDAD systems were investigated. Batch assays revealed that nitrite and nitrate were the preferential options in the SDAD system with single and multiple electron acceptors, respectively. Synchronous nitrogen and sulfur removal was successfully achieved in continuous flow experiments with multiple electron acceptors, and the system could adapt well to high concentrations of sulfide, nitrate and nitrite (i.e., 720, 108 and 64.8 mg L-1, respectively), with the predominant genera shifting from Thiobacillus (48.88%) at the initial stage to unclassified_p_Firmicute (34.24%) and Syner-01 (12.31%) at the last stage. This work provides a fundamental basis for applying and regulating SDAD with multiple electron acceptors for the remediation of nitrogen- and sulfide- laden wastewaters.

An enantioselective arylative dearomatization reaction of β-naphthols with quinone monoimides has been developed for the first time using a chiral phosphoric acid as the catalyst, the desired enantioenriched cyclohexadienones were prepared with excellent yields and enantioselectivities by a domino Michael addition and aromatization process (up to 99 % yield, up to 98 % ee). This process is operationally simple and readily scaled up, as well as a broad substrate scope which includes 1-substituted-2-naphthols with/without 3-substituents. Furthermore, this organocatalytic procedure allows the lowering of catalyst loading to 0.5 mol % without considerable loss in reactivity and enantioselectivity.

The aim of this study was to clarify the microRNA (miRNA) expression profiles of RAW264.7 macrophages infected by Candida albicans to elucidate the roles of differentially expressed miRNAs and to further explore the mechanisms underlying the immune response to C. albicans infection.High-throughput miRNA microarray analysis was performed to detect differentially expressed miRNAs in control and C. albicans-infected RAW264.7 cells. Quantitative real-time PCR analysis was used to verify the microarray results. Target genes of differentially expressed miRNAs were predicted with bioinformatics software. The cell biological processes and signaling pathways of these miRNA-targeted genes involved in C. albicans infection were predicted by gene ontology (GO) enrichment and pathway analyses.Significant upregulation of eight miRNAs (mmu-miR-140-5p, mmu-miR-96-5p, mmu-miR-8109, mmu-miR-466i-3p, mmu-miR-222-5p, mmu-miR-301b-3p, mmu-miR-466g, and mmu-miR-7235-5p) and downregulation of eight miRNAs (mmu-miR-3154, mmu-miR-223-3p, mmu-miR-494-3p, mmu-miR-6908-5p, mmu-miR-188-5p, mmu-miR-6769b-5p, mmu-miR-7002-5p, and mmu-miR-1224-5p) were observed, as compared with the control (fold change ≥2.0 and P 0.05). GO analysis revealed that both mmu-miR-140-5p and mmu-miR-223-3p participated in immune responses, inflammatory reactions, and cell apoptosis in C. albicans infection. Also, the MAPK signaling pathway was found to play an important role in the immune response against C. albicans infection.This study revealed comprehensive expression and functional profiles of differentially expressed miRNAs in macrophage RAW264.7 cells infected by C. albicans. These findings should help to further elucidate the mechanisms underlying the immune response to C. albicans infection.

The aim of this study was to observe the effect of baicalin on the growth state of attention deficit hyperactivity disorder animal model and its regulation on Ca MKⅡand ERK1/2.In the present study,a total of 40 SHR rats were randomly divided into model group,methylphenidate hydrochloride group,and low,medium,and high dose baicalin groups,with 8 rats in each group.Eight WKYrats were selected as a normal control group.The methylphenidate hydrochloride group(0.07 g·L~(-1))and the low(3.33 g·L~(-1)),medium(6.67 g·L~(-1)),and high dose(10 g·L~(-1))baicalin groups received corresponding drugs by gavage administration according to the body weight(0.015 m L·g~(-1)),while the normal group and the model group received the same volume of normal saline by gavage.Thegavage administration lasted for 4 weeks,twice a day.The body weight of the rats and the amount of remaining feed were weighed daily,and the growth state of the rats was statistically evaluated weekly.Percoll density gradient centrifugation was used to prepare brain synaptosomes and an electron microscope was used to observe their structures.The Ca MKⅡand ERK1/2 protein and mRNA expression levels were detected with Western blot and Real-time PCR methods,respectively.RESULTS: showed that baicalin did not affect the normal eating and weight gain of rats,and the weight gain of rats was even more significant than that in the normal group(P0.05).In the study of its effects on Ca MKⅡand ERK1/2 protein expression in rat synaptosomes,the expression of both proteins in each drug-administered group was higher than that in the model group(P0.05);besides,the expression levels of Ca MKⅡand ERK1/2 protein were significantly increased in both baicalin high dose group and the methylphenidate hydrochloride group(P0.05).The relative expression of Ca MKⅡand ERK1/2 mRNA in synaptosome was detected by PCR.The results showed that medium and high doses of baicalin and methylphenidate hydrochloride significantly increased the relative expression of Ca MKⅡand ERK1/2 mRNA in synaptosomes of SHR rats(P0.05).In conclusion,baicalin does not affect the normal growth and development of SHR rats,so it is safe for administration.Both baicalin and methylphenidate hydrochloride could up-regulate the relative expression of Ca MKⅡand ERK1/2 in mRNA and protein,and the pharmacodynamic stability of baicalin is in a dose-dependent manner to certain extent.

Association of both iron/hepcidin and apolipoprotein E (ApoE) with development of Alzheimer disease (AD) and atherosclerosis led us to hypothesize that ApoE might be required for body iron homeostasis. Here, we demonstrated that ApoE knock-out (KO) induced a progressive accumulation of iron with age in the liver and spleen of mice. Subsequent investigations showed that the increased iron in the liver and spleen was due to phosphorylated extracellular regulated protein kinases (pERK) mediated up-regulation of transferrin receptor 1 (TfR1), and nuclear factor erythroid 2-related factor-2 (Nrf2)-dependent down-regulation of ferroportin 1. Furthermore, replenishment of ApoE could partially reverse the iron-related phenotype in ApoE KO mice. The findings imply that ApoE may be essential for body iron homeostasis and also suggest that clinical late-onset diseases with unexplained iron abnormality may partly be related to deficiency or reduced expression of ApoE., Graphical abstract Image 1, Highlights • Apolipoprotein E deficiency induces a progressive increase in tissue iron contents with age in mice. • ApoE−/− induced a progressive accumulation of iron with age in the liver and spleen of mice. • The increased iron was due to upregulation of TfR1 and downregulation of Fpn1. • Replenishment of ApoE could partially reverse the iron-related phenotype in ApoE KO mice. • ApoE may be essential for body iron homeostasis.

Semi-solid alloy slurries with different temperature distributions have diverse flow patterns of the slurries during die casting filling process. This different flow patterns can lead to various degrees of front separation of the slurry metal from the die cavity during die filling process. This separation can result in air entrapment, which is one of the origins for gas porosities and blisters occurred during followed heat treatment. Therefore, in this paper, the effects of slurry temperature distribution on filling patterns during die casting process were investigated. Based on partial filling experiments, positive and negative gradient temperature distribution, together with two homogeneous conditions 575°C, 579°C were compared by computer simulation. The results indicate that the positive gradient temperature condition of 357.0 slurry is more suitable for the semi-solid die casting of the connector, and 7 °C temperature gradient in slurry is appropriate for good filling.

A crucial problem concerned with the semi-solid forming process is the liquid segregation phenomena during shape formation, especially for rheo-casting process. Liquid segregation occurs due to the separation phenomena of the solid grain and the liquid phase. In this work, using commercial finite element software, the liquid segregation during rheo-casting process was numerically investigated by Eulerian-granular multiphase model based on the comparable results of single phase model, Eulerian-granular two-phase and three-phase model, along with Eulerian-granular DDPM three-phase model. In the study, solid grains and liquid phases were regarded as rigid material and non-Newtonian fluid at microscale, separately. This validation was experimentally proved and also compared to the proposed relationship of power law, Herschel-Bulkley model with yield stress at macroscale.

A novel two-stage reheating process with new alloy design has been developed to improve the microstructure morphology of semisolid Al-Si casting aluminum alloy for thixoforming. The process consists of first reheating the material to the liquidus temperature, holding for 5 min, and then lowering to the predetermined two-stage reheating temperature between 843–863 K and holding for 10 min. The experimentally-obtained grain diameter, roundness, and the amount of liquid trapped within the solid phase were characterized, along with the microstructure obtained using the traditional feedstock reheating process. The Wilcox test (with α = 0.05) was then applied to statistically analyze the measured differences in the microstructures obtained using the two different processing routes. It was found that a refined near-spherical structure with uniform globule size, higher sphericity, lower coarsening rate constant, and less entrapped liquid was obtained via the new two-stage reheating process in comparison with the microstructure obtained using the traditional feedstock reheating process.

Baicalin is a flavonoid purified from Scutellaria baicalensis Georgi. It possesses a variety of pharmacological properties, such as anti-inflammatory, antioxidant, antiapoptotic, and neuro-protective properties, and provides protection against cerebral hemorrhage. However, it is seldom considered a therapeutic in mental disorders. Recent studies showed that baicalin protects cerebral functions against ischemia and has sedative and anxiolytic-like effects. Animal experiments showed that it protects dopaminergic neurons in the striatum, hippocampus and substantia nigra. It also has effects such as anti-depressive and anti-epileptic and offers resistance to Parkinson's disease. Attention deficit hyperactivity disorder (ADHD) pathogenesis is closely related to dopamine deficiency. However, the therapeutic effect of baicalin in ADHD has not been studied. We hypothesize that baicalin may protect dopaminergic neurons and increase brain dopamine levels, thus serving as an effective novel treatment for ADHD.

An enantioselective sulfenylation of β-naphthols has been developed for the first time using a newly synthesized cinchona-derived thiourea as the catalyst and N-(arylthio) succinimide (or phthalimide) as an electrophilic sulfur source. Various enantioenriched naphthalenones with an S-containing all-substituted stereocenter were prepared via a dearomatization strategy under mild reaction conditions.

The gene therapy of cancer, due to the limit of its efficiency and safety, has not been widely used in clinical. Recently, bacterial magnetic particles (BMPs), which are membrane-bound nanocrystals found in magnetotactic bacteria, have been exploited as a new gene delivery system. However, its application on gene therapy remains to be explored. In our previous study, we found that a combination of cecropin B (ABPs) and apoptin (VP3) could serve as an effective gene therapeutic agent. Thus, in this study, we used BMPs to deliver the co-expression plasmid of these two gene, namely pVAX1-VA, and evaluated its therapeutic effect on human hepatocellular carcinoma (HepG2). Our results showed that BMPs significantly improved the efficiency of gene transfection (almost 3-fold than Lipofectamine 2000 at 48 h, P .001), which led to stronger apoptosis (in a peak almost 2-fold than Lipofectamine 2000-pVAX1-VA, P .01) and growth inhibition of HepG2 cells. More importantly, compared with Lipofectamine 2000-pVAX1-VA group, BMP-pVAX1-VA strikingly inhibited tumor growth (0.60 ± 0.09 g vs. 0.88 ± 0.11 g, P .05) in nude mouse tumor models and increased the tumor-infiltrating lymphocytes considerably without apparent cytotoxicity. These findings suggest that BMPs could be an attractive gene delivery system for gene therapy and provide a potential available treatment for human hepatocellular carcinoma and maybe some other kinds of tumors.

Objective To explore whether there are stem cells in the endosalpinx, and to compare the biological properties between the mucosal stem cells (MuSCs) and mesenchymal stem cells (MeSCs) obtained from the fallopian tube for the purpose of providing experimental basis for clinical application. Methods In this study, we isolated, cultured and amplified human MuSCs and MeSCs in vitro, and compared the cell morphology, cell phenotype, colony forming efficiency, proliferation and differentiation capacities of MuSCs and MeSCs. Results Both MeSCs and MuSCs showed a similar elongated morphology, but the arrangement of MuSCs were more uniform than that of MeSCs. MuSCs showed a significantly higher proliferation capacity compared with MeSCs. Colony forming unit-fibroblast analysis further showed that more colonies formed with MuSCs than that of MeSCs, with a significant statistical difference. However, FTMSC and FMSC showed similar immunophenotypes. In vitro assays revealed that both types of cells showed the potential of adipogenic, osteogenic, and chondrogenic differentiation. Conclusions Stem cells were found in the fallopian tube mucosa, and MuSCs have stronger proliferation capacity than MeSCs, thus they possess a higher value for clinical application. DOI: 10.11855/j.issn.0577-7402.2015.04.08

Thermal simulation compression tests were performed on semi-solid billet in order to observe and investigate the behavior of 6061 aluminum alloys while varying the processing parameters such as apparent viscosity, the shear rate and the temperature. Specimens of 6061 aluminum alloys were characterized with their semi-solid behavior during partial melting and holding in the semi-solid state. Furthermore, the constitutive equation of semi-solid 6061 aluminum alloys was investigated. Moreover, the tests allow the apparent viscosity and shear rate of the alloys to be determined as a function of the solid volume fraction and strain rate together with the geometry behavior of the specimen. Utilizing these parameters, semi-solid die casting process of 6061 aluminum alloys could be simulated by the change of the solid volume fractions.

Here, we report a fiber-optic point-based sensor to measure temperature and weight based on correlated specklegrams induced by spatial multimode interference. The device is realized simply by splicing a multimode fiber (MMF) to a single-mode fiber (SMF) with a core offset. A series of experiments demonstrates the approximately linear relation between the correlation coefficient and variation. Furthermore, we show the potential applications of the refractive index sensing of our device by disconnecting the splicing point of MMF and SMF. A modification of the algorithm in order to improve the sensitivity of the sensor is also discussed at the end of the paper.

OBJECTIVE: To investigate the effect of baicalin on the behavioral characteristics of rats with attention deficit hyperactivity disorder (ADHD), and to provide a basis for further research on baicalin in the treatment of ADHD. METHODS: A total of 40 SHR rats were randomly divided into model group, methylphenidate hydrochloride (MPH) group, and low-, medium-, and high-dose baicalin groups, with 8 rats in each group. Eight WKY rats were selected as normal control group. The rats in the MPH group (0.07 mg/mL) and the low-(3.33 mg/mL), medium-(6.67 mg/mL), and high-dose (10 mg/mL) baicalin groups were given the corresponding drugs (1.5 mL/100 g) by gavage twice a day, and those in the normal control group and the model group were given an equal volume of normal saline by gavage twice a day. The course of treatment was 4 weeks for all groups. The open field test was performed to observe total moving distance and average moving speed on day 0 of experiment and at 7, 14, 21, and 28 days after gavage and to evaluate the control effects of drugs on hyperactivity and impulsive behavior. The Morris water maze test was used to observe the latency, time spent in the target quadrant, and number of platform crossings and to evaluate the effects of drugs on attention. RESULTS: The open field test showed that the model group and the drug treatment groups had a significantly longer total moving distance and a significantly higher average moving speed than the normal control group on day 0 (P < 0.05). On day 7, the MPH group had significant reductions in total moving distance and average moving speed compared with the model group (P < 0.05). On day 14, the MPH group and the high-dose baicalin group had significant reductions in total moving distance and average moving speed compared with the model group (P < 0.05). The data on days 21 and 28 showed that compared with the model group, the low-, medium-, and high-dose baicalin groups had gradual reductions in total moving distance and average moving speed (P < 0.05). The water maze test showed that compared with the model group, the MPH group and the medium-and high-dose baicalin groups had a significantly longer time spent in the target quadrant (P < 0.05), and the MPH group and the high-dose baicalin group had a significantly higher proportion of the moving distance in the target quadrant in total moving distance (P < 0.05). The high-dose baicalin group had the highest number of platform crossings among all groups (P < 0.05). CONCLUSIONS: Both baicalin and MPH can regulate the motor ability and learning and memory abilities of SHR rats with ADHD and thus control the core symptoms of ADHD, i.e., hyperactivity, impulsive behavior, and inattention. Baicalin exerts its effect in a dose-dependent manner, and high-dose baicalin has the most significant effect, but compared with MPH, it needs a longer time to play its therapeutic effect.

The applications of specklegram analysis techniques have been developed recently. In this paper, we represent a fiber-optic method to measure the temperature through the analysis of output specklegrams. The proposed all-fiber device excites higher-order modes through splicing a multimode fiber (MMF) to a single-mode fiber (SMF) with a core offset. The basic principle of the sensor is based on determining the change occurring to a speckle pattern when the fiber is heated under different temperature. This change in the speckle pattern is computed by comparing it with a reference speckle pattern recorded at a known temperature and therefore can be related to the temperature change. The experiments manifest the approximately linear relation between correlation coefficient and temperature. Furthermore, we also demonstrate the effects of other related parameters to the sensor.

OBJECTIVE: To study the effect of baicalin on synaptosomal adenosine triphosphatase (ATPase) and lactate dehydrogenase (LDH) and its regulatory effect on the adenylate cyclase (AC) /cyclic adenosine monophosphate (cAMP) /protein kinase A (PKA) signaling pathway in rats with attention deficit hyperactivity disorder (ADHD). METHODS: A total of 40 SHR rats were randomly divided into five groups:ADHD model, methylphenidate hydrochloride treatment (0.07 mg/mL), and low-dose (3.33 mg/mL), medium-dose (6.67 mg/mL), and high-dose (10 mg/mL) baicalin treatment (n=8 each). Eight WKY rats were selected as normal control group. Percoll density gradient centrifugation was used to prepare brain synaptosomes and an electron microscope was used to observe their structure. Colorimetry was used to measure the activities of ATPase and LDH in synaptosomes. ELISA was used to measure the content of AC, cAMP, and PKA. RESULTS: Compared with the normal control group, the ADHD model group had a significant reduction in the ATPase activity, a significant increase in the LDH activity, and significant reductions in the content of AC, cAMP, and PKA (P < 0.05). Compared with the ADHD model group, the methylphenidate hydrochloride group and the medium-and high-dose baicalin groups had a significant increase in the ATPase activity (P < 0.05), a significant reduction in the LDH activity (P < 0.05), and significant increases in the content of AC, cAMP, and PKA (P < 0.05). Compared with the methylphenidate hydrochloride group, the high-dose baicalin group had significantly greater changes in these indices (P < 0.05). Compared with the low-dose baicalin group, the high-dose baicalin group had a significant increase in the ATPase activity (P < 0.05); the medium-and high-dose baicalin groups had a significant reduction in the LDH activity (P < 0.05) and significant increases in the content of AC, cAMP, and PKA (P < 0.05). Compared with the medium-dose baicalin group, the high-dose baicalin group had a significant increase in the ATPase activity (P < 0.05). CONCLUSIONS: Both methylphenidate hydrochloride and baicalin can improve synaptosomal ATPase and LDH activities in rats with ADHD. The effect of baicalin is dose-dependent, and high-dose baicalin has a significantly greater effect than methylphenidate hydrochloride. Baicalin exerts its therapeutic effect possibly by upregulating the AC/cAMP/PKA signaling pathway.

In the present study, the short- and long-term effects of Zn(II) on the anaerobic ammonium oxidation (anammox) performance and sludge characteristics were evaluated. The anammox activity decreased with increasing Zn(II) concentration and pre-exposure time in short-term tests. The half maximal inhibitory concentration (IC50) of Zn(II) was found to be 25.0 mg L(-1). The 24 and 48-h pre-exposure time was a restricted factor impacting the anammox activity, and washing the inhibited sludge with buffer solution only worked under 0 and 24-h pre-exposure time. The anammox sludge could tolerate 5 mg L(-1) Zn(II) but was suppressed at 8 mg L(-1). The inhibited performance could be remitted, as the combination strategies were applied, and after the short term of recovery period, the inhibited sludge characteristics were remitted to the normal.

In order to improve the automation level for the control system of liquid fermentation of a company in Hubei province, and combine with the requirements of the company, a distributed control system of liquid fermentation is designed. The control system is composed of host computer based on WinCC, and the slave computer is S7-300 PLC of SIEMENS. The fermentation parameters, including rotation speed, temperature, pH, DO, O2, CO2, can be real-time online collected, and realize the frequency control of motor and precise control of temperature. The experiment result shows that the system runs stably and credibly, the parameters can be collected accurately and the temperature control accuracy has been achieved to be ±0.1°C.