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Current surveillance strategies for hepatocellular carcinoma (HCC) among patients with nonalcoholic fatty liver disease (NAFLD) are insufficient. This study aimed to investigate the diagnostic performance of alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-II (PIVKA-II), lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and their combinations in HCC underlying NAFLD patients.Serologic AFP, AFP-L3, and PIVKA-II levels in NAFLD patients with and without HCC were measured. By receiver operating characteristic (ROC) analyses, the area under the curve (AUC), sensitivity, and specificity were obtained to evaluate the diagnostic accuracy of each biomarker and their combinations.This study was conducted on 139 patients with NAFLD-HCC and 345 NAFLD controls. The elevation of these three biomarkers was observed in patients with NAFLD-HCC compared to those in NAFLD controls (all P0.001). When they were analyzed individually, PIVKA-II showed the best performance in diagnosing any-stage HCC with an AUC of 0.869, followed by AFP (0.763; vs. PIVKA-II, P0.001) and AFP-L3 (0.689; vs. PIVKA-II, P0.001). When they were analyzed in combination, AFP + PIVKA-II yielded the highest AUC (0.906), followed by AFP + PIVKA-II + AFP-L3 (0.904; vs. AFP + PIVKA-II, P = 0.086), PIVKA-II + AFP-L3 (0.881; vs. AFP + PIVKA-II, P0.001), and AFP + AFP-L3 (0.759; vs. AFP + PIVKA-II, P0.001). Similar findings were obtained in the subgroup with early-stage NAFLD-HCC, as well as the non-cirrhotic subgroup.These data validated the better diagnostic ability of PIVKA-II than AFP or AFP-L3 alone for diagnosing any-stage HCC among patients with NAFLD, and the combination of AFP + PIVKA-II significantly improved the diagnostic accuracy of NAFLD-HCC.

With rapid economic development, an increasing number of people suffer from mental health diseases, which are gradually receiving the attention of society. However, basic data from surveys of mental disorders are limited. Composite influent samples were collected from 26 wastewater treatment plants in 23 major cities in China. The concentrations of the psychoactive drugs diphenhydramine, fluoxetine, doxepin, imipramine, sulpiride, zolpidem, carbamazepine, and flunitrazepam in the wastewater were determined. The detection frequency of diphenhydramine, sulpiride, and carbamazepine was close to 100 %, whereas that of the compounds was lower than 35 %. Carbamazepine had the highest mean consumption (31.1 mg/d/1000 people), followed by diphenhydramine (10.4 mg/d/1000 people) and sulpiride (11.3 mg/d/1000 people). Wastewater-based epidemiology (WBE) estimates of the average use of the three drugs were lower than those from the drug statistics data. Consumption of diphenhydramine in northern China was higher than that in southern China. A correlation analysis of psychotropic and illicit drugs revealed a correlation between sulpiride and heroin use, which may be related to the adverse effects of sulpiride treatment after heroin withdrawal. Psychotropic drug use is associated with both economic and social factors. We found associations between the use of the three drugs and age, occupation, and obesity, which are risk factors for mental disorders. The results showed that the monitoring of psychotropic drug using WBE has a certain reference value for public health care and for improving the understanding of mental disorders.

This paper proposed a novel method for the production of biodiesel from soy sauce residue under supercritical carbon dioxide for the first time. The effect of several parameters, such as the size of raw material, reaction pressure, temperature, time, and methanol/oil molar ratio were carefully optimized by single-factor experiments. The results showed that the optimized parameters were particle size 60 meshes, reaction pressure 16 MPa, temperature 100 °C, time 180min and methanol/oil molar ratio 35:1. Under this optimal conditions, biodiesel yield is as high as 96.21%. Furthermore, in order to better understand the advantages of this process, the mechanism and result of this process were compared with existing technology. The findings of this paper demonstrated that the soy sauce residue which was commonly considered as a waste can be efficiently converted to biodiesel by this method.

Wound healing is a complex and long-term process consisting of hemostasis, inflammation, proliferation, and maturation/remodeling. These four stages overlap and influence each other; they affect wound healing in different ways, and if they do not function perfectly, they may cause scarring, proliferative scarring and keloid formation. A therapeutic target affecting wound healing in multiple ways will help the healing process proceed more effectively. DPP-4/CD26 is a multifunctional dimorphic glycoprotein widely distributed on the surface of a variety of cells, including fibroblasts and keratin-forming cells. It has been found to affect periwound inflammation, re-epithelialization, extracellular matrix secretion and skin fibrosis and is a potential target for promoting wound healing and inhibiting scar formation. After presenting a brief introduction of the wound healing process and DPP-4/CD26, this paper summarizes the effects of DPP-4/CD26 on cells involved in different stages of wound healing and discusses the feasibility of DPP-4/CD26 as a multifunctional target for the treatment of wound healing and inhibition of scar formation.

Background: The outbreak of the coronavirus disease 2019 (COVID-19) in China has been basically controlled However, the worldwide COVID-19 cases are increasing

Background: The outbreak of coronavirus disease 2019 (COVID-19) initially appeared and has most rapidly spread in Wuhan, China. The case fatality rate is the most direct indicator to assess the hazards of an infectious disease. We aimed to estimate the instant fatality rate and cure rate of COVID-19 in Wuhan City and its affiliated Hubei Province. Methods: We collected the daily case notification data of COVID-19 from Dec 8, 2019 to Feb 29, 2020 in Wuhan City and Hubei Province officially announced by the Chinese authority. The numbers of daily confirmed/deaths/cured cases and the numbers of daily cumulative confirmed/deaths/cured cases were obtained. The death time and cure time of COVID-19 patients were calculated based on the dates of diagnosis, death and discharge of individual cases. Then the estimated diagnosis dates of deaths and cured cases were obtained on the basis of the median death or medium cure time, respectively. Finally, the instant fatality rate of COVID-19 was calculated according to the numbers of deaths and cured cases on the same estimated diagnosis dates. Findings: From Jan 1, 2020 to Feb 13, 2020 in Wuhan City, the instant fatality rate of COVID-19 was 3.4%～19.5% and the instant cured rate was 80.0%～96.6%. The average fatality rate reached 12.3% while the average cure rate was 87.7%. During the same period in Hubei Province, the instant fatality rate of confirmed cases was 3.8%～16.6% and the instant cured rate was 83.4%～96.6%. The average fatality rate and the average cure rate were 10.0% and 90.0%, respectively. Interpretation: The fatality rate and cure rate of COVID-19 in Wuhan City and Hubei Province were underestimated. Wuhan showed higher fatality rate and cure rate than the whole Hubei Province did. Funding Statement: None. Declaration of Interests: The authors declare no competing interests.

Overproduction of inflammatory mediators contributes to uncontrolled inflammation during endotoxin shock. Cystathionine-γ-lyase (CSE), an enzyme involved in hydrogen sulfide (H2S) biosynthesis, has potential anti-inflammatory activity in a variety of inflammatory diseases. Jumonji domain-containing protein 3 (JMJD3), a histone 3 Lys27 (H3K27) demethylase, has been implicated in macrophage activation, but its function in CSE-mediated anti-inflammatory activities remains unknown. In the present study CSE was found to be upregulated in macrophages and mouse lipopolysaccharide (LPS) challenge models. LPS stimulation also enhanced the activation of JMJD3 and decreased H3K27me3 levels. JMJD3 knockdown upregulated H3K27me3 levels and attenuated the LPS-mediated inflammatory response. CSE knockout amplified the inflammatory cascade by increasing JMJD3 expression in septic mice. Similarly, enhanced production of inflammatory mediators by macrophages was mitigated by CSE overexpression via inhibition of JMJD3 expression. This is the first report indicating that inflammation enhanced CSE/H2S system biosynthesis, that in turn attenuated the LPS-triggered inflammatory response by regulating JMJD3 expression. Thus, the CSE/H2S system represents an epigenetic-based modification mechanism to prevent uncontrolled inflammation.

Water loss is a key factor in pericarp browning during storage and transportation of litchi and longan fruit. However, whether this water loss is of biological significance is unclear. The loss of water in different tissues during browning of the two fruit, and the relationship between water loss and seed vigor were investigated. The pericarp of both fruit lost 60% of water after 4 days at 20 °C without packaging, in contrast, water loss in the aril and seed was insignificant. Water loss led to browning, a denser and thinner pericarp, correlating with a decrease in permeability to water of the pericarp. The seeds maintained 40% water content and 80% of them germinated when kept in the intact fruit after 12 days. In contrast, bare seeds stored without package retained 20% water content and germinated less than 10%. Germination was negatively correlated with fruit decay index. Phenols extracted from the pericarp after browning inhibited the growth of Peronophythora litchii more than those extracted before browning. Pericarp browning triggered by water loss of the tissue after harvest maintains seed vigor by preventing of dehydration and infection of the seeds.

Radioactive 85Kr is a major gaseous fission product emitted into the air by the nuclear fuel reprocessing industry. Measuring atmospheric 85Kr has applications in environmental monitoring, atmospheric transport model validation and dating of environmental water samples, including groundwater, sea water and glacier ice. We present an ultra-sensitive method for fast analysis of atmospheric 85Kr at 10−5 parts per trillion level. This method is based on laser cooling and trapping and is capable of counting individual 85Kr atoms. Measurements at the 3% precision level can be made on krypton extracted from 1L STP of air with a turnaround time of 1.5 h. Moreover, we have realized a system for continuous air sampling over days to weeks. Based on this atom-counting technology and a portable air sample integrator we have realized atmospheric 85Kr baseline monitoring in Hefei, China, for over 20 months. The technological advances presented in this work lay the ground for a global atmospheric 85Kr monitoring network.

Background: Hypertrophic scar (HS) is characterized by the increased proliferation and decreased apoptosis of myofibroblasts. Myofibroblasts, the main effector cells for dermal fibrosis, develop from normal fibroblasts. Thus, the stimulation of myofibroblast apoptosis is a possible treatment for HS. We aimed to explore that whether over-activated myofibroblasts can be targeted for apoptosis by anticancer drug elesclomol. Methods: 4’,6-diamidino-2-phenylindole staining, flow cytometry, western blotting, collagen gel contraction and immunofluorescence assays were applied to demonstrate the proapoptotic effect of elesclomol in scar derived myofibroblasts and TGF-β1 induced myofibroblasts. The therapeutic potential of elesclomol was investigated by establishing rabbit ear hypertrophic scar models. Findings: Both 4′,6-diamidino-2-phenylindole staining and flow cytometry indicated that elesclomol targets myofibroblasts in vitro. Collagen gel contraction assay showed that elesclomol inhibited myofibroblast contractility. Flow cytometry and western blot analysis revealed that elesclomol resulted in excessive intracellular levels of reactive oxygen species(ROS), and caspase-3 and cytochrome c proteins. Moreover, compared with the control group, the elesclomol group had a significantly lower scar elevation index in vivo. Immunofluorescence assays for TUNEL and α-smooth muscle actin indicated that elesclomol treatment increased the number of apoptotic myofibroblasts. Interpretation: The above results indicate that elesclomol exerted a significant inhibitory effect on HS formation via targeted myofibroblast apoptosis associated with increased oxidative stress. Thus, elesclomol is a promising candidate drug for the treatment of myofibroblast-related diseases such as HS. Funding Statement: Funding for this study was provided by the Natural Science Foundation of China (81770876), Natural Science Foundation of Jiangsu Province (Grant BK20191141). Declaration of Interests: The authors declare no competing interests with relevance to this study. Ethics Approval Statement: The study protocols were approved by the ethics committee of the Affiliated Hospital of Jiangnan University. The study purpose and the procedures involved were explained to the patients, who all consented in writing to the use of their resected tissue specimens in this study. The animal experiments were approved by the Experimental Animal Committee of Jiangnan University.

Monitoring the consumption of pharmaceuticals and licit drugs is important for assessing the needs of public health owing to the impact on individuals as well as society. The present work applied wastewater-based epidemiology to profile the spatial patterns of metformin, nicotine, and caffeine use and their correlations. Influent wastewater samples were collected from 27 wastewater treatment plants in 22 typical Chinese cities that covered all geographic regions of the country. The consumption of metformin ranged from 0.02 g/d/1000 inh to 8.92 g/d/1000 inh, whereas caffeine and nicotine consumption ranged from 4.33 g/d/1000 inh to 394 g/d/1000 inh and 0.17 g/d/1000 inh to 1.88 g/d/1000 inh, respectively. There were significant regional differences in the consumption of caffeine, with the highest consumption in East China and the lowest consumption in Northeast China. The consumption and concentration of caffeine were related to the gross domestic product and per capita disposable income of urban residents, respectively. There was a correlation between the concentrations of caffeine and cotinine (a nicotine metabolite), thereby indicating that individuals that use one of these substances are likely to use the other substance. A significant relationship was found between the concentration of metformin and cotinine, thereby implying that the use of tobacco may be correlated with type 2 diabetes. Co-analysis of these substances in wastewater may provide a more accurate picture of substance use situations within different communities and provide more information on human health, human behavior, and the economy. This report describes the newest study related to the consumption of metformin among the general population in China.

Background Epidermal growth factor receptor (EGFR) is an effective molecular target for cancer treatment. Boehmenan, a lignan from the dried stems of Clematis armandii , exhibited the potent cytotoxic effects against many cancer cell lines in previous studies. However, the effects and underlying mechanism of boehmenan on non-small cell lung cancer (NSCLC) remains unclear. Purpose The present study was designed to determine the in vitro anti-cancer properties and underlying molecular mechanisms of boehmenan on A549 NSCLC cells. Study design/methods Cellular viability and chemoattractive properties of macrophages were investigated by using MTT and transwell migration assay, respectively. Mitochondrial membrane potential (Δ Ψ m ), apoptotic ratio, and cell cycle were measured by flow cytometry. Protein expression was visualized by Western blot using specific antibodies. Results Boehmenan concentration-dependently suppressed proliferation and induced G 1 phase arrest in A549 NSCLC cells, which were accompanied by reduction of migration, colony formation and increase of apoptosis in A549 cells. In addition, boehmenan treatment markedly modulated apoptosis-related protein (p53, p21, cleaved caspase 3, and cleaved PARP) and cyclin D1 expression and induced Δ Ψ m collapse in a concentration dependent manner. Furthermore, boehmenan concentration-dependently inhibited EGF-induced activation of EGFR and its downstream signaling molecules, including MEK, Akt, ERK1/2, and STAT3. Conclusion Taken together, our results suggested that boehmenan-mediated anti-tumor property was mediated by modulation of mitochondria and EGFR signaling pathway in A549 NSCLC cells.

Background (7R, 8S)-9-Acetyl-dehydrodiconiferyl alcohol (ADDA), a novel lignan compound isolated from Clematis armandii Franch (Ranunculaceae) stems, has been found to exert potential anti-inflammatory activities in vitro. Purpose To investigate the pharmacological effects and molecular mechanisms of ADDA on lipopolysaccharide (LPS)-induced activation and migration of macrophages. Study design/methods Macrophages were stimulated with LPS in the presence or absence of ADDA. Expression of inflammatory mediators, including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nitric oxide (NO) were measured by Western blot and commercial NO detection kit. Cellular viability and chemotactic properties of macrophages were investigated using MTT and transwell migration assays. The activation and expression of mitogen activated protein kinases, nuclear factor-κB (NF-κB), protein kinase B (Akt), Src, and focal adhesion kinase (FAK) were analyzed by Western blot. Results Non-toxic concentrations (12.5–50 µM) of ADDA concentration-dependently inhibited expression/release of inflammatory mediators (COX-2, iNOS, and NO), suppressed Akt and c-jun N-terminal kinase 1/2 (JNK) phosphorylation, and NF-κB activation in LPS-stimulated macrophages. In addition, ADDA blocked LPS-mediated macrophage migration and this was associated with inhibition of LPS-induced Src and FAK phosphorylation as well as Src expression in a concentration dependent manner. Notably, the inhibitory effects of ADDA on iNOS, NO, and Src could be mimicked by a Src inhibitor PP2 or an iNOS inhibitor l -NMMA. Conclusion Our results suggested that ADDA attenuated LPS-induced inflammatory responses in macrophages and cell migration, at least in part, through inhibition of NF-κB activation and modulation of iNOS/Src/FAK axis.

Three kinds of turbines (Vestas V-47:660 kW, Enercon E−40:600 kW, Vestas V-66:1.75 MW) were installed on three selected sites (Mailiao, Jhongtun, Chunfong) as wind power plants for electricity generation on an island. However, such power plants including turbines in establishment and operation during entire life cycle are bound to consume energy and produce carbon emission, causing environmental problems. Therefore, the purpose of the present study is to evaluate the effects of three wind power plants on the environment during their entire life cycle. This paper made the calculations of carbon emissions of three wind power plants, and compared and discussed the occupied shares of each primary energy input in manufacture, construction, operation and disposal phases using the methods of mathematics and materials input-output life cycle assessment. The results show that the CO2 emission factor of three systems was on average 3.9 g/kWh for the whole life cycle. The average CO2 emission intensity of all raw materials was 1.35 kg/kg. The occupied share of CO2 emissions in manufacturing, construction, and decommissioning phases was 44%, 16%, and 40% respectively. The primary energy input intensity was on average 0.0625 MJ/kWh of three systems for whole life cycle. The average energy input intensity of three systems was 21.48 MJ/kg. The combined CO2 emission intensity of all steel materials was 1.98 kg/kg. The demands for materials and energy inputs, and carbon emissions are positively related to the rated power value of a wind turbine. Wind power has a priority to produce clean energy, and can significantly decrease CO2 emissions.

The risk of cardiovascular complications in diabetic patients is mainly associated with endothelial dysfunction. Reduced number of EPCs and impaired function of EPCs in diabetes result in imbalance of endothelial homeostasis and dysfunction of vessels. In patients with diabetes mellitus, plasma levels of asymmetric dimethylarginine (ADMA) were elevated, while the expression and activity of dimethylarginine dimethylaminohydrolase (DDAH) were reduced. In the present study, we investigated the role of the DDAH2/ADMA pathway in the senescence of EPCs in type 2 diabetic patients and cultured EPCs treated with high glucose. The results showed that the percentage of senescent EPCs increased while the expression of DDAH2 decreased concomitantly with an increase in the plasma levels of ADMA in patients with type 2 diabetes mellitus (T2DM). Similar results were seen in cultured EPCs treated with high glucose. Exogenous application of ADMA accelerated the senescence of EPCs in a dose-dependent manner, and overexpression of DDAH2 inhibited high glucose-induced EPCs senescence. In addition, it has also been reported that DDAH/ADMA pathway is regulated by silent information regulator 1 (SIRT1) in endothelial cell. In the present study, we found decreased expression of SIRT1 both in T2DM patients and EPCs pretreated with high glucose. And resveratrol (activating SIRT1) inhibited high glucose-induced EPCs senescence by upregulating the expression of DDAH2 and decreasing the levels of ADMA. Taken together, we concluded that DDAH2/ADMA is involved in the accelerated senescence of EPCs in diabetes, which is associated with the activation of SIRT1.

Our previous studies showed that rutaecarpine (Rut) protected against myocardial ischemia/reperfusion (I/R) injury, which was associated with activation of transient receptor potential vanilloid subtype 1 (TRPV1). Recently, TRPV1 activation was also reported to exert neuroprotective effects. The present study was to investigate the effect of Rut on hypoxia/reoxygenation (H/R)-induced apoptosis in primary rat hippocampal neurons. Three-hour hypoxia (1% O2) and consequent 24-h reoxygenation significantly increased the apoptotic death of hippocampal neurons as evidenced by increases in both TUNEL-positive cell number and caspase-3 activity. However, pretreatment with Rut (1–10 mM) or caspase-3 specific inhibitor DEVD-CHO could markedly attenuate H/R-induced apoptosis in neurons. Rut markedly induced the phosphorylation of Akt and PI3K inhibitor LY294002 prevented the survival effect of Rut on neurons. Intracellular oxidative stress was significantly induced after H/R, which was inhibited by Rut and LY294002 as well as antioxidant PDTC. TRPV1 antagonist capsazepine or intracellular Ca 2þ chelator BAPTA/AM could abolish these effects of Rut mentioned above. In summary, the present data suggest that Rut inhibits H/R-induced apoptosis of hippocampal neurons via TRPV1-[Ca 2þ ]i-dependent and PI3K/Akt signaling pathway, which is related to inhibiting oxidative stress and caspase-3 activation.

Tetrahydroacridine (THA), or Cognex, is currently awaiting FDA approval for the treatment of Alzheimer's disease. In addition to reports indicating that THA improves the symptoms of patients with Alzheimer's disease, we have found that THA possesses potent antiplatelet activity. THA produced dose-dependent inhibition of human platelet aggregation induced by collagen, ADP, A23187, and phorbol ester. THA, when added to activated platelets, dispersed the platelet aggregates. We have also examined the effects of THA on intracellular Ca++ mobilization, ATP release, and production of cyclic AMP.

Tetramethylpyrazine (TMPZ) is an active component that can be extracted from certain plants. In China, this herbal extract is used to treat ischemic vascular diseases. We have assessed the antithrombotic activity of TMPZ using arterial and venous thrombosis models in rats. Antithrombotic activity of TMPZ is at least partly due to its potent antiplatelet effect. We have shown that TMPZ inhibits platelet aggregation induced by ADP, collagen, thrombin, and A23187 but not by diacylglycerol (DAG). Platelets that were induced to produce maximal aggregation could be dispersed by the addition of TMPZ. Platelets could then be reaggregated by the addition of DAG. Studies monitoring intracellular ionized calcium suggest that TMPZ inhibits calcium mobilization from both the extracellular medium and from intracellular stores.