Using firefly algorithm to optimally size a hybrid renewable energy system constrained by battery degradation and considering uncertainties of power sources and loads.

In this paper, the planning of a hybrid system of wind turbine units, photovoltaic panels, and battery storage is presented by taking into account the limitation of the storage degradation. The scheme minimizes the construction and maintenance cost of power sources and storage equipment. The constraints of the problem include the operating model of the mentioned elements, the limitation of the number of the mentioned elements, the limitation of the storage degradation, and the power balance in the hybrid system. This scheme is subject to uncertainties of the demand and output power generation of wind turbines and photovoltaics, which are modeled using a scenario-based stochastic optimization. The problem has a mixed-integer non-linear structure, and the paper adopts the firefly algorithm to solve the problem. The contributions of the paper include considering the degradation model of the battery, presenting a stochastic modelling for planning the islanded system, and taking into account the uncertainties of load and renewable power. Finally, based on the numerical results, a low planning cost is obtained for the hybrid system in the case of using renewable resources. Batteries are capable of providing flexibility for the hybrid system so that they can cover oscillations of renewable power with respect to the load. The firefly algorithm can find a reliable optimal solution. Stochastic modeling raises the planning cost of the islanded system in comparison to the deterministic model, but it yields a more reliable solution. The battery degradation model incurs no additional costs in system planning, although it offers a far more precise representation of the battery's behavior.

Predicting the Sauter Mean Diameter of Swirl Cup Airblast Fuel Injector Based on Backpropagation (BP) Neural Network Model.

This study was dedicated to introducing a new method for predicting the Sauter mean diameter (SMD) buildup in the swirl cup airblast fuel injector. There have been considerable difficulties with predicting SMD mainly because of complicated flow characteristics in a spray. Therefore, the backpropagation (BP) neural network-based machine learning was applied for the prediction of SMD as a function of geometry, condition parameters, and axial distance such as primary swirl number, secondary swirl number, venturi angle, mass flow rate of fuel, and relative air pressure. SMD was measured by a phase Doppler particle analyzer (PDPA). The results show that the prediction accuracy of the trained BP neural network was excellent with a coefficient of determination (R2) score of 0.9599, root mean square error (RMSE) score of 1.4613, and overall relative error within 20%. Through sensitivity analysis, the relative air pressure drop and primary swirl number were the largest and smallest factors affecting the value of SMD, respectively. Finally, the prediction accuracy of the BP neural network model is far greater than the current prediction correlations. Moreover, for the predicting target in the present study, the BP neural network shows the advantages of a simple structure and short running time compared with PSO-BP and GRNN. All these prove that the BP neural network is a novel and effective way to predict the SMD of droplets generated by a swirl cup airblast fuel injector.

BM-MSCs overexpressing the Numb enhance the therapeutic effect on cholestatic liver fibrosis by inhibiting the ductular reaction.

BACKGROUND: Cholestatic liver fibrosis (CLF) is caused by inflammatory destruction of the intrahepatic bile duct and abnormal proliferation of the small bile duct after cholestasis. Activation of the Notch signaling pathway is required for hepatic stem cells to differentiate into cholangiocytes during the pathogenesis of CLF. Our previous research found that the expression of the Numb protein, a negative regulator of Notch signaling, was significantly reduced in the livers of patients with primary biliary cholangitis and CLF rats. However, the relationship between the Numb gene and CLF is largely unclear. In this study, we investigated the role of the Numb gene in the treatment of bile duct ligation (BDL)-induced CLF. METHODS: In vivo, bone marrow-derived mesenchymal stem cells (BM-MSCs) with Numb gene overexpression or knockdown obtained using lentivirus transfection were transplanted into the livers of rats with BDL-induced CLF. The effects of the Numb gene on stem cell differentiation and CLF were evaluated by performing histology, tests of liver function, and measurements of liver hydroxyproline, cytokine gene and protein levels. In vitro, the Numb gene was overexpressed or knocked down in the WB-F344 cell line by lentivirus transfection, Then, cells were subjected immunofluorescence staining and the detection of mRNA levels of related factors, which provided further evidence supporting the results from in vivo experiments. RESULTS: BM-MSCs overexpressing the Numb gene differentiated into hepatocytes, thereby inhibiting CLF progression. Conversely, BM-MSCs with Numb knockdown differentiated into biliary epithelial cells (BECs), thereby promoting the ductular reaction (DR) and the progression of CLF. In addition, we confirmed that knockdown of Numb in sodium butyrate-treated WB-F344 cells aggravated WB-F344 cell differentiation into BECs, while overexpression of Numb inhibited this process. CONCLUSIONS: The transplantation of BM-MSCs overexpressing Numb may be a useful new treatment strategy for CLF.

Amygdalin Ameliorates Liver Fibrosis through Inhibiting Activation of TGF-ß/Smad Signaling.

OBJECTIVE: To observe the effect of amygdalin on liver fibrosis in a liver fibrosis mouse model, and the underlying mechanisms were partly dissected in vivo and in vitro. METHODS: Thirty-two male mice were randomly divided into 4 groups, including control, model, low- and high-dose amygdalin-treated groups, 8 mice in each group. Except the control group, mice in the other groups were injected intraperitoneally with 10% carbon tetrachloride (CCl4)-olive oil solution 3 times a week for 6 weeks to induce liver fibrosis. At the first 3 weeks, amygdalin (1.35 and 2.7 mg/kg body weight) were administered by gavage once a day. Mice in the control group received equal quantities of subcutaneous olive oil and intragastric water from the fourth week. At the end of 6 weeks, liver tissue samples were harvested to detect the content of hydroxyproline (Hyp). Hematoxylin and eosin and Sirius red staining were used to observe the inflammation and fibrosis of liver tissue. The expressions of collagen I (Col-I), alpha-smooth muscle actin (α-SMA), CD31 and transforming growth factor ß (TGF-ß)/Smad signaling pathway were observed by immunohistochemistry, quantitative real-time polymerase chain reaction and Western blot, respectively. The activation models of hepatic stellate cells, JS-1 and LX-2 cells induced by TGF-ß1 were used in vitro with or without different concentrations of amygdalin (0.1, 1, 10 µmol/L). LSECs. The effect of different concentrations of amygdalin on the expressions of liver sinusoidal endothelial cells (LSECs) dedifferentiation markers CD31 and CD44 were observed. RESULTS: High-dose of amygdalin significantly reduced the Hyp content and percentage of collagen positive area, and decreased the mRNA and protein expressions of Col-I, α-SMA, CD31 and p-Smad2/3 in liver tissues of mice compared to the model group (P<0.01). Amygdalin down-regulated the expressions of Col-I and α-SMA in JS-1 and LX-2 cells, and TGFß R1, TGFß R2 and p-Smad2/3 in LX-2 cells compared to the model group (P<0.05 or P<0.01). Moreover, 1 and 10 µmol/L amygdalin inhibited the mRNA and protein expressions of CD31 in LSECs and increased CD44 expression compared to the model group (P<0.05 or P<0.01). CONCLUSIONS: Amygdalin can dramatically alleviate liver fibrosis induced by CCl4 in mice and inhibit TGF-ß/Smad signaling pathway, consequently suppressing HSCs activation and LSECs dedifferentiation to improve angiogenesis.

SNS-032 attenuates liver fibrosis by anti-active hepatic stellate cells via inhibition of cyclin dependent kinase 9.

Liver fibrosis is a common pathological process of all chronic liver diseases. Hepatic stellate cells (HSCs) play a central role in the development of liver fibrosis. Cyclin-dependent kinase 9 (CDK9) is a cell cycle kinase that regulates mRNA transcription and elongation. A CDK9 inhibitor SNS-032 has been reported to have good effects in anti-tumor. However, the role of SNS-032 in the development of liver fibrosis is unclear. In this study, SNS-032 was found to alleviate hepatic fibrosis by inhibiting the activation and inducing the apoptosis of active HSCs in carbon tetrachloride-induced model mice. In vitro, SNS-032 inhibited the activation and proliferation of active HSCs and induced the apoptosis of active HSCs by downregulating the expression of CDK9 and its downstream signal transductors, such phosphorylated RNA polymerase II and Bcl-2. CDK9 short hairpin RNA was transfected into active HSCs to further elucidate the mechanism of the above effects. Similar results were observed in active HSCs after CDK9 knockdown. In active HSCs with CDK9 knockdown, the expression levels of CDK9, phosphorylated RNA polymerase II, XIAP, Bcl-2, Mcl-1, and ɑ-SMA significantly decreased, whereas those of cleaved-PARP1 and Bax decreased prominently. These results indicated that SNS-032 is a potential drug and CDK9 might be a new prospective target for the treatment of liver fibrosis.

Research Progress in Chinese Medicine Preparations for Promoting Blood Circulation and Removing Blood Stasis for Cirrhotic Patients with Portal Vein Thrombosis Following Splenectomy.

This article presented an overview of the therapeutic effects of Chinese medicine (CM) preparations for promoting blood circulation and removing blood stasis for patients with portal vein thrombosis (PVT) after splenectomy. Based on published clinical researches of CM preparations for PVT after splenectomy in patients with cirrhotic portal hypertension (CPH), this paper evaluated the incidence of PVT, and explored potential active components and mechanisms of CM preparations. Safflower Yellow Injection, Danshen Injection () Danhong Injection (), and Compound Danshen Dropping Pill () achieved good curative effect alone or combined with anticoagulant therapy. In addition, Compound Biejia Ruangan Tablet () and Anluo Huaxian Pill () can also significantly improve the hemodynamic disorders of portal vein system in patients with cirrhosis. Considering the role of CM preparations in ameliorating the incidence of PVT after splenectomy in patients with CPH, we suggested that future research should provide more attention to CM alone or CM combined with anticoagulant for cirrhosis with PVT.

Exploring sustainable solutions for the water environment in Chinese and Southeast Asian cities.

Water is essential for human activities and economic development, and the water environment significantly influences ecological balance and global climate. China and Southeast Asia are the most populous areas in the world, and their water resources are deteriorating day by day. We focus on five representative cities such as, Beijing, Jakarta, Hanoi, Kathmandu and Manila to investigate water-environmental problems with the ultimate goal of providing recommendations for sustainable urban water management. The study found that (1) the water environment of all cities has been polluted to varying levels, while the pollution has improved in Beijing and Jakarta, and the situation in other regions is severe. (2) The aquatic biodiversity has reduced, and its pollution is mainly caused by organic pollutants and decreasing river flow. In addition, numerous people live in megacities without access to clean surface water or piped drinking water, which greatly increases the use of groundwater. Further, frequent floods in the world leads to serious damage to urban infrastructure and further deterioration of water environment quality. To address these problems, countries and organizations have begun to construct wastewater treatment plants and develop water-saving technology to ensure healthy and sustainable development of water environment. The results and practical recommendations of this study can provide scientific insights for future research and management strategies to address water quality challenges during ongoing policy debates and decision-making processes.

SCO6992, a Protein with ß-Glucuronidase Activity, Complements a Mutation at the absR Locus and Promotes Antibiotic Biosynthesis in Streptomyces coelicolor.

Streptomyces coelicolor is a filamentous soil bacterium producing several kinds of antibiotics. S. coelicolor abs8752 is an abs (antibiotic synthesis deficient)-type mutation at the absR locus; it is characterized by an incapacity to produce any of the four antibiotics synthesized by its parental strain J1501. A chromosomal DNA fragment from S. coelicolor J1501, capable of complementing the abs- phenotype of the abs8752 mutant, was cloned and analyzed. DNA sequencing revealed that two complete ORFs (SCO6992 and SCO6993) were present in opposite directions in the clone. Introduction of SCO6992 in the mutant strain resulted in a remarkable increase in the production of two pigmented antibiotics, actinorhodin and undecylprodigiosin, in S. coelicolor J1501 and abs8752. However, introduction of SCO6993 did not show any significant difference compared to the control, suggesting that SCO6992 is primarily involved in stimulating the biosynthesis of antibiotics in S. coelicolor. In silico analysis of SCO6992 (359 aa, 39.5 kDa) revealed that sequences homologous to SCO6992 were all annotated as hypothetical proteins. Although a metalloprotease domain with a conserved metal-binding motif was found in SCO6992, the recombinant rSCO6992 did not show any protease activity. Instead, it showed very strong ß-glucuronidase activity in an API ZYM assay and toward two artificial substrates, p-nitrophenyl-ß-D-glucuronide and AS-BI-ß-D-glucuronide. The binding between rSCO6992 and Zn2+ was confirmed by circular dichroism spectroscopy. We report for the first time that SCO6992 is a novel protein with ß-glucuronidase activity, that has a distinct primary structure and physiological role from those of previously reported ß-glucuronidases.

Thymosin ß4 increases cardiac cell proliferation, cell engraftment, and the reparative potency of human induced-pluripotent stem cell-derived cardiomyocytes in a porcine model of acute myocardial infarction.

Rationale: Previous studies have shown that human embryonic stem cell-derived cardiomyocytes improved myocardial recovery when administered to infarcted pig and non-human primate hearts. However, the engraftment of intramyocardially delivered cells is poor and the effectiveness of clinically relevant doses of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in large animal models of myocardial injury remains unknown. Here, we determined whether thymosin ß4 (Tb4) could improve the engraftment and reparative potency of transplanted hiPSC-CMs in a porcine model of myocardial infarction (MI). Methods: Tb4 was delivered from injected gelatin microspheres, which extended the duration of Tb4 administration for up to two weeks in vitro. After MI induction, pigs were randomly distributed into 4 treatment groups: the MI Group was injected with basal medium; the Tb4 Group received gelatin microspheres carrying Tb4; the CM Group was treated with 1.2 × 108 hiPSC-CMs; and the Tb4+CM Group received both the Tb4 microspheres and hiPSC-CMs. Myocardial recovery was assessed by cardiac magnetic resonance imaging (MRI), arrhythmogenesis was monitored with implanted loop recorders, and tumorigenesis was evaluated via whole-body MRI. Results: In vitro, 600 ng/mL of Tb4 protected cultured hiPSC-CMs from hypoxic damage by upregulating AKT activity and BcL-XL and promoted hiPSC-CM and hiPSC-EC proliferation. In infarcted pig hearts, hiPSC-CM transplantation alone had a minimal effect on myocardial recovery, but co-treatment with Tb4 significantly enhanced hiPSC-CM engraftment, induced vasculogenesis and the proliferation of cardiomyocytes and endothelial cells, improved left ventricular systolic function, and reduced infarct size. hiPSC-CM implantation did not increase incidence of ventricular arrhythmia and did not induce tumorigenesis in the immunosuppressed pigs. Conclusions: Co-treatment with Tb4-microspheres and hiPSC-CMs was safe and enhanced the reparative potency of hiPSC-CMs for myocardial repair in a large-animal model of MI.

Fasudil prevents liver fibrosis via activating natural killer cells and suppressing hepatic stellate cells.

BACKGROUND: Fasudil, as a Ras homology family member A (RhoA) kinase inhibitor, is used to improve brain microcirculation and promote nerve regeneration clinically. Increasing evidence shows that Rho-kinase inhibition could improve liver fibrosis. AIM: To evaluate the anti-fibrotic effects of Fasudil in a mouse model of liver fibrosis induced by thioacetamide (TAA). METHODS: C57BL/6 mice were administered TAA once every 3 d for 12 times. At 1 wk after induction with TAA, Fasudil was intraperitoneally injected once a day for 3 wk, followed by hematoxylin and eosin staining, sirius red staining, western blotting, and quantitative polymerase chain reaction (qPCR), and immune cell activation was assayed by fluorescence-activated cell sorting. Furthermore, the effects of Fasudil on hepatic stellate cells and natural killer (NK) cells were assayed in vitro. RESULTS: First, we found that TAA-induced liver injury was protected, and the positive area of sirius red staining and type I collagen deposition were significantly decreased by Fasudil treatment. Furthermore, western blot and qPCR assays showed that the levels of alpha smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP-2), MMP-9, and transforming growth factor beta 1 (TGF-ß1) were inhibited by Fasudil. Moreover, flow cytometry analysis revealed that NK cells were activated by Fasudil treatment in vivo and in vitro. Furthermore, Fasudil directly promoted the apoptosis and inhibited the proliferation of hepatic stellate cells by decreasing α-SMA and TGF-ß1. CONCLUSION: Fasudil inhibits liver fibrosis by activating NK cells and blocking hepatic stellate cell activation, thereby providing a feasible solution for the clinical treatment of liver fibrosis.

Continental transmission of emerging COVID-19 on the 38° north latitude.

BACKGROUND: As COVID-19 has become a pandemic emerging infectious disease it is important to examine whether there was a spatiotemporal clustering phenomenon in the globe during the rapid spread after the first outbreak reported from southern China. MATERIALS AND METHODS: The open data on the number of COVID-19 cases reported at daily basis form the globe were used to assess the evolution of outbreaks with international air link on the same latitude and also including Taiwan. The dynamic Susceptible-Infected-Recovered model was used to evaluate continental transmission from December 2019 to March 2020 before the declaration of COVID-19 pandemic with basic reproductive number and effective reproductive number before and after containment measurements. RESULTS: For the initial COVID-19 outbreak in China, the estimated reproductive number was reduced from 2.84 during the overwhelming outbreaks in early January to 0.43 after the strict lockdown policy. It is very surprising to find there were three countries (including South Korea, Iran, and Italy) and the Washington state of the USA on the 38° North Latitude involved with large-scale community-acquired outbreaks since the first imported COVID-19 cases from China. The propagation of continental transmission was augmented from hotspot to hotspot with higher reproductive number immediately before the declaration of pandemic. By contrast, there was not any large community-acquired outbreak in Taiwan. CONCLUSION: The propagated spatiotemporal transmission from China to other hotspots may explain the emerging pandemic that can only be exempted by timely border control and preparedness of containment measurements according to Taiwan experience.

Integrated proteomics and metabolomics analysis of tea leaves fermented by Aspergillus niger, Aspergillus tamarii and Aspergillus fumigatus.

Post-fermented Pu-erh tea (PFPT) is a microbially-fermented tea with distinct sensory qualities and multiple health benefits. Aspergillus are the dominant fungi in the fermentation and the main contributors to the characteristics of PFPT, so their underlying functions warrant detailed study. Here, tea leaves were fermented by Aspergillus niger, Aspergillus tamarii and Aspergillus fumigatus, and resulting samples (designated as Asn, Ast and Asf, respectively) were analyzed by proteomic and metabolomic methods. Changes to the composition of flavonoids, glycerophospholipids, organo-oxygen compounds and fatty acids resulting from Aspergillus fermentation were observed. Carbohydrate-active enzymes, e.g., endoglucanases and cellulases, for degradation of cellulose, starch, lignin, pectin, xylan and xyloglucan were identified. Glycoside hydrolase, glycosyltransferases, tannase, laccases, vanillyl-alcohol oxidases and benzoquinone reductase were identified and hypothesized to catalyze hydrolysis, oxidation, polymerization and degradation of phenolic compounds. Together, functions of Aspergillius were demonstrated as production of enzymes to change concentrations and compositions of metabolites in tea leaves.

Pharmacological Effects of Salvianolic Acid B Against Oxidative Damage.

Salvianolic acid B (Sal B) is one of the main active ingredients of Salvia miltiorrhiza, with strong antioxidant effects. Recent findings have shown that Sal B has anti-inflammatory, anti-apoptotic, anti-fibrotic effects and can promote stem cell proliferation and differentiation, and has a beneficial effect on cardiovascular and cerebrovascular diseases, aging, and liver fibrosis. Reactive oxygen species (ROS) include oxygen free radicals and oxygen-containing non-free radicals. ROS can regulate cell proliferation, survival, death and differentiation to regulate inflammation, and immunity, while Sal B can scavenge oxygen free radicals by providing hydrogen atoms and reduce the production of oxygen free radicals and oxygen-containing non-radicals by regulating the expression of antioxidant enzymes. The many pharmacological effects of Sal B may be closely related to its elimination and inhibition of ROS generation, and Nuclear factor E2-related factor 2/Kelch-like ECH-related protein 1 may be the core link in its regulation of the expression of antioxidant enzyme to exert its antioxidant effect. What is confusing and interesting is that Sal B exhibits the opposite mechanisms in tumors. To clarify the specific target of Sal B and the correlation between its regulation of oxidative stress and energy metabolism homeostasis will help to further understand its role in different pathological conditions, and provide a scientific basis for its further clinical application and new drug development. Although Sal B has broad prospects in clinical application due to its extensive pharmacological effects, the low bioavailability is a serious obstacle to further improving its efficacy in vivo and promoting clinical application. Therefore, how to improve the availability of Sal B in vivo requires the joint efforts of many interdisciplinary subjects.

Hepatic stem cell Numb gene is a potential target of Huang Qi Decoction against cholestatic liver fibrosis.

Numb is a negative regulator of Notch signal pathway. Previous study has demonstrated that Notch signal pathway activation is required for hepatic progenitor cell (HPC) differentiating into cholangiocytes in cholestatic liver fibrosis (CLF), and Huang Qi Decoction (HQD) could prevent CLF through inhibition of the Notch signal pathway. However, the role of Numb in HQD against CLF is yet unclear. Thus, CLF rats transplanted into rat bone marrow-derived mesenchymal stem cells with knocked down Numb gene (BMSCNumb-KD) were treated with HQD. Simultaneously, Numb gene knockdown was also performed in WB-F344 cell line and then treated with refined HQD in vitro. In vivo study revealed that liver fibrosis was inhibited by HQD plus BMSCNumb-KD treatment, while Hyp content in liver tissue, the gene and protein expression of α-SMA, gene expression of Col I, TNF-α, and TGF-ß1 were increased compared to that in HQD group. Furthermore, Notch signal pathway was inhibited by HQD plus BMSCNumb-KD, while the protein expression of Numb was decreased and RBP-Jκ and Hes1 was increased compared to that in HQD group. In vitro, HQD reduced the differentiation of WB-F344 cells into cholangiocyte phenotype, while this effect was attenuated after Numb-knockdown. This study highlights that the absence of hepatic stem cell Numb gene decreases effect of HQD against CLF, which give rise the conclusion that Numb might be a potential target for HQD against CLF.

Light-Induced Caspase-3-Responsive Chimeric Peptide for Effective PDT/Chemo Combination Therapy with Good Compatibility.

Activated doxorubicin (DOX) often has severe systemic toxicity and side effects due to its inability to distinguish tumor cells from normal cells, which seriously affects the prognosis of patients. Here, we synthesized an inactivated a DOX prodrug that could be selectively activated by a light-induced caspase-3 enzyme in the tumor site. In the absence of light, this uniformly dispersed nanoparticle avoided the unnecessary toxicity under physiological conditions. Upon the laser irradiating to the tumor area of interest, the nanoparticles can produce a large amount of reactive oxygen species (ROS) to induce cell apoptosis and activate caspase-3 enzyme to release DOX selectively. Meanwhile, the produced ROS can also combine with activated DOX to cause more potent tumor damage. The experiments demonstrated that the light can effectively activate DOX drug through a series of cascade events and the subsequent synergistic therapy both in vitro and in vivo. This strategy achieved excellent therapeutic outcomes and minimal adverse effects, which should significantly improve the dilemma of traditional chemotherapy.

A simple method for in vitro preparation of natural killer cells from cord blood.

BACKGROUND: Cord Blood (CB) has been considered a promising source of natural killer (NK) cells for cellular immunotherapy. However, it is difficult to expand the large numbers of highly pure NK cells from CB without cell sorting and feeder cells/multiple cytokines. In this study, we try to develop a simple, safe and economical method for ex vivo expansion and purification of NK cells from CB without cell sorting and feeder cells/multiple cytokines. RESULTS: The large numbers (mean: 1.59 × 1010) of highly pure (≥90%) NK cells from CB could be obtained through interleukin-2, group A streptococcus and zoledronate stimulation of mononuclear cells using the 21-day culture approach. When compared to resting NK cells, expanded NK cells were a higher expression of activating receptors CD16, NKG2D, NKp30, NKp44, NKp46 and activating markers CD62L and CD69, while the inhibitory receptors, CD158a and CD158b remained largely unchanged. In addition, these cells showed a higher concentration of IFN-γ, TNF-α and GM-CSF secretion and cytotoxicity to K562 cells and acute myeloid leukemia targets than resting NK cells. CONCLUSION: We develop a simple, safe and economical method to obtain high yield, purity, and functionality NK cells from CB without cell sorting and feeder cells/multiple cytokines.

Prescription practices in the treatment of agitation in newly hospitalized Chinese schizophrenia patients: data from a non-interventional naturalistic study.

BACKGROUND: Data on the pharmacological management of acute agitation in schizophrenia are scarce. The aim of this study is to investigate the prescription practices in the treatment of agitation in Chinese patients with schizophrenia. METHODS: We conducted a large, multicenter, observational study in 14 psychiatry hospitals in China. Newly hospitalized schizophrenia patients with the PANSS-EC total score ≥ 14 and a value ≥4 on at least one of its five items were included in the study. Their drug treatments of the first 2 weeks in hospital were recorded by the researchers. RESULTS: Eight hundred and 53 patients enrolled in and 847 (99.30%) completed the study. All participants were prescribed antipsychotics, 40 (4.72%) were prescribed benzodiazepine in conjunction with antipsychotics and 81 were treated with modified electric convulsive therapy (MECT). Four hundred and 12 (48.64%) patients were prescribed only one antipsychotic, in the order of olanzapine (120 patients, 29.13%), followed by risperidone (101 patients, 24.51%) and clozapine (41 patients, 9.95%). About 435 (51.36%) participants received antipsychotic polypharmacy, mostly haloperidol + risperidone (23.45%), haloperidol+ olanzapine (17.01%), olanzapine+ ziprasidone (5.30%), haloperidol + clozapine (4.37%) and haloperidol + quetiapine (3.90%). Binary logistic regression analysis suggests that a high BARS score (OR 2.091, 95%CI 1.140-3.124), severe agitation (OR 1.846, 95%CL 1.266-2.693), unemployment or retirement (OR 1.614, 95%CL 1.189-2.190) and aggressiveness on baseline (OR 1.469, 95%CL 1.032-2.091) were related to an increased antipsychotic polypharmacy odds. Male sex (OR 0.592, 95%CL 0.436-0.803) and schizophrenia in older persons (age ≥ 55 years, OR 0.466, 95%CL 0.240-0.902) were less likely to be associated with antipsychotic polypharmacy. CONCLUSION: The present study demonstrates that monotherapy and polypharmacy display equally common patterns of antipsychotic usage in managing agitation associated with schizophrenia in China. The extent and behavioral activities of agitation and several other factors were associated with polypharmacy.

Yiguanjian decoction enhances fetal liver stem/progenitor cell-mediated repair of liver cirrhosis through regulation of macrophage activation state.

AIM: To investigate whether Yiguanjian decoction (YGJ) has an anti-liver cirrhotic effect and whether it regulates hepatic stem cell differentiation. METHODS: A rat model of liver cirrhosis was established via subcutaneous injection of carbon tetrachloride (CCl4) for 8 wk. From the beginning of the ninth week, the rats received 2-acetylaminofluorene (2-AAF) by oral gavage and a DLK-1+ fetal liver stem/progenitor cell (FLSPC) transplant or an FLSPC transplant in combination with YGJ treatment for 4 wk. In vitro, lipopolysaccharide (LPS)-activated macrophages were co-cultured with WB-F344 cells, and the differentiation of WB-F344 cells was observed in the presence and absence of YGJ treatment. RESULTS: FLSPC transplantation improved liver function and histopathology, and inhibited the activation of the non-canonical Wnt signaling pathway, while activating the canonical Wnt signaling pathway. YGJ enhanced the therapeutic effects of FLSPCs and also promoted the liver regeneration differentiation of FLSPCs into hepatocytes. In vitro, LPS-activated macrophages promoted the differentiation of WB-F344 cells into myofibroblasts, and the canonical Wnt signaling was inhibited while the non-canonical Wnt signaling was activated in WB-F344 cells. YGJ suppressed the activation of macrophages and then inhibited non-canonical Wnt signaling and promoted canonical Wnt signaling. CONCLUSION: YGJ enhances FLSPC-mediated repair of liver cirrhosis through regulation of macrophage activation state, and YGJ in combination with stem cell transplantation may be a suitable treatment for end-stage liver cirrhosis.

Research progress on signaling pathways in cirrhotic portal hypertension.

Portal hypertension (PHT) is an important consequence of liver cirrhosis, which can lead to complications that adversely affect a patient's quality of life and survival, such as upper gastrointestinal bleeding, ascites, and portosystemic encephalopathy. In recent years, advances in molecular biology have led to major discoveries in the pathological processes of PHT, including the signaling pathways that may be involved: PI3K-AKT-mTOR, RhoA/Rho-kinase, JAK2/STAT3, and farnesoid X receptor. However, the pathogenesis of PHT is complex and there are numerous pathways involved. Therefore, the targeting of signaling pathways for medical management is lagging. This article summarizes the progress that has been made in understanding the signaling pathways in PHT, and provides ideas for treatment of the disorder.

Tumor-triggered transformation of chimeric peptide for dual-stage-amplified magnetic resonance imaging and precise photodynamic therapy.

Despite the great success in clinical magnetic resonance imaging (MRI), Gd3+-based contrast agents still suffer from low proton relaxation efficiency, rapid metabolic clearance as well as poor sensitivity. In this work, we designed a matrix metalloproteinase-2 (MMP-2) responsive chimeric peptide for dual-stage-amplified MRI and precise photodynamic therapy. Both in vitro and in vivo studies indicated that this chimeric peptide could self-assembly into spherical nanoparticles at physiological condition with r1 value of 28.17 mM-1s-1. Meanwhile, the spherical shape endowed chimeric peptide with efficient tumor accumulation via enhanced penetration and retention (EPR) effect. Importantly, the overexpressed MMP-2 in tumor region could specifically hydrolyze chimeric peptide, leading to sphere-to-fiber transformation. This transformation enhanced both the tumor accumulation and the relaxivity of contrast agent. Consequently, the r1 value was remarkably elevated to 51.52 mM-1s-1, which guided precise photodynamic therapy. This tumor microenvironment-triggered transformable strategy should show great potential for tumor-targeted imaging and phototherapy.