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The increasing concentration of nitrate in groundwater and surface water exerts negative effects on the aquatic environment and the safety of drinking water supplies. Efficient water decontaminatio...

Black pepper (Piper nigrum L.) has been commonly utilized in food preparation and traditional medicine in several countries. Seven new amide alkaloids, pipernigramides A-G (3, 10, 38, and 41-44), a new piperic ester, pipernigrester A (48), along with 47 known compounds were isolated from the EtOH extract of P. nigrum. The inhibitory effects on nitric oxide (NO) of all compounds were then evaluated. Among the tested compounds, three of them (42-44) significantly inhibited inducible nitric oxide synthase (iNOS)-mediated NO (IC50 = 4.74 ± 0.18, 4.08 ± 0.19, and 3.71 ± 0.32 μM, respectively), and IL-1β, IL-6, TNF-α, and PGE2 release in RAW 264.7 cells stimulated by lipopolysaccharide. Moreover, 42-44 suppressed IκB degradation and further inhibited the cytosol-nucleus translocation of the p65 subunit by targeting IKK-β. In the carrageenan-induced paw edema test, 42-44 demonstrated anti-inflammatory effects as well. These results indicate that all three compounds from P.nigrum have the potential anti-inflammatory effects.

We aimed to investigate the effectiveness of endovascular therapy (EVT) versus intravenous thrombolysis (IVT) in patients with basilar artery occlusion (BAO), based on the information of advanced imaging.We analyzed data of stroke patients with radiologically confirmed BAO within 24 hours. BAO subjects were categorized into "top-of-the-basilar" syndrome (TOBS) and other types. An initial infarct size of70ml and a ratio of ischemic tissue to infarct volume of ≥1.8 was defined as "target mismatch." The primary outcome was a good outcome, defined as a modified Rankin Scale score of 0 to 3 at 3 months. Propensity score adjustment and inverse probability of treatment weighting (IPTW) propensity score methods were used.Among 474 BAO patients, 93 (19.6%) were treated with IVT prior to EVT, 91 (19.2%) were treated with IVT alone, 95 (20.0%) were treated with EVT alone, and 195 (41.1%) were treated with antithrombotic therapy. In IPTW analyses, we found no benefit of EVT over IVT for good outcome in either TOBS patients (odds ratio = 1.08, 95% confidence interval [CI] = 0.88-1.31) or those with other types (odds ratio = 1.13, 95% CI = 0.94-1.36). However, in patients with other types, if there existed a target mismatch, EVT was independently related to good outcome (odds ratio = 1.46, 95% CI = 1.17-1.81).The "target mismatch profile" seems to be a possible candidate selection standard of EVT for those with other types of BAO. Future studies should separate TOBS from other types of BAO, and try to use advanced imaging. ANN NEUROL 2022;92:97-106.

With reference to the production process documented in Chinese Pharmacopoeia, this paper prepared the calibrator samples of Xiaochaihu Granules from multiple batches and established a method for fingerprint analysis and content determination that could be used to evaluate Xiaochaihu Granules available in market. Multiple batches of Chinese herbal pieces contained in Xiaochaihu Granules were collected for preparing the calibrator samples according to the process in Chinese Pharmacopoeia. Following the establishment of fingerprints for calibrator samples by UHPLC, the method for determining the contents of saikosaponin B2, saikosaponin B1, baicalin, wogonoside, baicalein, liquiritin, glycyrrhizin G2 and glycyrrhizic acid in Xiaochaihu Granules was established. The experimental results showed that the fingerprints of calibrator samples had 26 common peaks, covering the chemical compounds of main herbs Bupleuri Radix, Scutellariae Radix, Changii Radix, Glycyrrhizae Radix et Rhizoma, and Rhizoma Zingiberis Recens. The similarity of fingerprints for 47 batches of Xiaochaihu Granules from 31 companies with the calibrator sample fingerprint ranged from 0.74 to 0.99, indicating good applicability of the established fingerprint. The contents of main components baicalin, saikosaponin B2, and glycyrrhizic acid in Xiaochaihu Granules were within the ranges of 22.917-49.108 mg per bag(RSD 19%), 0.28-2.19 mg per bag(RSD 62%), and 0.897-6.541 mg per bag(RSD 41%), respectively. The quality difference in saikosaponin B2, and glycyrrhizic acid among different manufacturers was significant. The fingerprint analysis and content determination method for calibrator samples of Xiaochaihu Granules prepared according to the production process in Chinese Pharmacopoeia has been proved suitable for evaluating the quality of Xiaochaihu Granules from different manufacturers. Saikosaponin B2, glycyrrhizic acid, and liquiritin should be added as content control indicators for Xiaochaihu Granules, aiming to further improve the product quality.

The core prescriptions and formulation characteristics in the treatment of edema by traditional Chinese medicine(TCM) masters were analyzed through data mining and their mechanisms were explored by network pharmacology. We collected journal reports on the treatment of edema by TCM masters in three sessions from China National Knowledge Infrastructure(CNKI) and constructed a database by Traditional Chinese Medicine Inheritance Support System 3.0. The prescriptions in the case studies were analyzed by association rules and k-means clustering. The chemical components and targets of Chinese medicines in core prescriptions were collected through TCMSP and TCMID. Edema-related targets were collected from DrugBank and GeneCards. The protein-protein interaction(PPI) network was constructed by STRING and the core targets were screened out. FunRich 3.1.3 was used to enrich the expression sites of core prescriptions. Metascape was used to perform Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis of intersection targets. Cytoscape 3.6.0 was used to visualize thequot;Chinese medicine-active ingredient-core target-pathwayquot; network. The results showed that 315 pieces of medical records in the treatment of edema by TCM masters were obtained and five core prescriptions were analyzed by association rules and k-means clustering. Core prescription 1 contained Poria, Atractylodis Macrocephalae Rhizoma, Astragali Radix, Alismatis Rhizoma, Glycyrrhizae Radix et Rhizoma, and Codonopsis Radix, involving 166 chemical components and 1 125 targets. Core prescription 2 contained Astragali Radix, Salviae Miltiorrhizae Radix et Rhizoma, Poria, Chuanxiong Rhizoma, Paeoniae Radix Rubra, and Angelicae Sinensis Radix, involving 138 chemical components and 1 112 targets. Core prescription 3 contained Poria, Salviae Miltiorrhizae Radix et Rhizoma, Astragali Radix, Atractylodis Macrocephalae Rhizoma, Alismatis Rhizoma, and Coicis Semen, involving 126 chemical components and 1 121 targets. Core prescription 4 contained Poria, Forsythiae Fructus, Atractylodis Macrocephalae Rhizoma, Imperatae Rhizoma, Cicadae Periostracum, and Coicis Semen, involving 58 chemical components and 820 targets. Core prescription 5 contained Poria, Atractylodis Macrocephalae Rhizoma, Astragali Radix, Alismatis Rhizoma, Trionycis Carapax, and Dioscoreae Rhizoma, involving 68 chemical components and 919 targets. The core targets of core prescriptions included AKT1, ALB, CASP3, MAPK3, EGFR, SRC, MAPK1, and TNF. The potential targets of core prescriptions in the treatment were highly expressed in the stomach, bladder, lung, and kidney. KEGG pathways were enriched in inflammation and cell cycle pathways, especially the inflammation-relation pathways. The therapeutic effect of core prescriptions on edema is presumedly achieved by tonifying the spleen, draining water, activating blood, and benefiting Qi to resist inflammation and regulate the immune system. This study is expected to provide references for the summary of TCM masters' experience and new drug development.

Huan Tang, Yizhuo Xie, Ming Zhu, Juan Jia, Rui Liu, Yujia Shen, Yucui Zheng, Xin Guo, Dongfanghui Miao, Jin Pei Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Jin Pei, Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, 1163 Xinmin Street, Changchun, 130021, People’s Republic of China, Tel +86 431 85619725, Email peijin@jlu.edu.cnPurpose: Ovarian cancer is the most lethal gynecologic malignancy. The combination of paclitaxel (PTX) and carboplatin (CBP) is the first-line remedy for clinical ovarian cancer. However, due to the limitations of adverse reaction and lacking of targeting ability, the chemotherapy of ovarian cancer is still poorly effective. Here, a novel estrone (ES)-conjugated PEGylated liposome co-loaded PTX and CBP (ES-PEG-Lip-PTX/CBP) was designed for overcoming the above disadvantages.Methods: ES-PEG-Lip-PTX/CBP was prepared by film hydration method and could recognize estrogen receptor (ER) over-expressing on the surface of SKOV-3 cells. The characterizations, stability and in vitro release of ES-PEG-Lip-PTX/CBP were studied. In vitro cellular uptake and its mechanism were observed by fluorescence microscope. In vivo targeting effect in tumor-bearing mice was determined. Pharmacokinetics and biodistribution were studied in ICR mice. In vitro cytotoxicity and in vivo anti-tumor efficacy were evaluated on SKOV-3 cells and tumor-bearing mice, respectively. Finally, the acute toxicity in ICR mice was explored for assessing the preliminary safety of ES-PEG-Lip-PTX/CBP.Results: Our results showed that ES-PEG-Lip-PTX/CBP was spherical shape without aggregation. ES-PEG-Lip-PTX/CBP exhibited the optimum targeting effect on uptake in vitro and in vivo. The pharmacokinetics demonstrated ES-PEG-Lip-PTX/CBP had improved the pharmacokinetic behavior. In vitro cytotoxicity showed that ES-PEG-Lip-PTX/CBP maximally inhibited SKOV-3 cell proliferation and its IC50 values was 1.6 times lower than that of non-ES conjugated liposomes at 72 h. The in vivo anti-tumor efficacy study demonstrated that ES-PEG-Lip-PTX/CBP could lead strong SKOV-3 tumor growth suppression with a tumor volume inhibitory rate of 81.8%. Meanwhile, acute toxicity studies confirmed that ES-PEG-Lip-PTX/CBP significantly reduced the toxicity of the chemo drugs.Conclusion: ES-PEG-Lip-PTX/CBP was successfully prepared with an optimal physicochemical and ER targeting property. The data of pharmacokinetics, anti-tumor efficacy and safety study indicated that ES-PEG-Lip-PTX/CBP could become a promising therapeutic formulation for human ovarian cancer in the future clinic.Graphical Abstract: Keywords: ovarian cancer, combination therapy, drug delivery system, liposome, estrogen receptor

The interaction of MPs and aromatic hydrocarbons in seawater and pure water was examined using experimental measurements, molecular dynamics (MD) simulations, and density functional theory (DFT) calculations in light of the potential health risks posed by microplastic (MPs)-associated aromatic hydrocarbon pollutants. Isothermal studies and MD simulations suggested that MPs have a stronger affinity for aromatic hydrocarbons in seawater. To uncover the mechanism, MPs' surface characteristics and their intermolecular interactions with aromatic hydrocarbons were examined. According to the research, MPs in seawater have less compact structure, bigger pores, and a higher specific surface area, all of which contribute to more sorption sites. Analysis of the intermolecular interaction indicated that MPs have a greater ability for molecular interactions in seawater and the interaction energy between MPs and aromatic hydrocarbons in seawater is higher. Additionally, seawater cations may act as bridges, which also accelerate sorption in seawater. In summary, this study provides a molecular-level understanding of MPs-aromatic hydrocarbons interaction and demonstrates that the interaction is stronger in seawater.

Cancer organoids generated from 3D in vitro cell cultures have contributed to the study of drug resistance. Maintenance of genomic and transcriptomic similarity between organoids and parental cancer allows organoids to have the ability of accurate prediction in drug resistance testing. Protocols of establishing therapy-sensitive and therapy-resistant organoids are concluded in two aspects, which are generated directly from respective patients' cancer and by induction of anti-cancer drug. Genomic and transcriptomic analyses and gene editing have been applied to organoid studies to identify key targets in drug resistance and FGFR3, KHDRBS3, lnc-RP11-536 K7.3 and FBN1 were found to be key targets. Furthermore, mechanisms contributing to resistance have been identified, including metabolic adaptation, activation of DNA damage response, defects in apoptosis, reduced cellular senescence, cellular plasticity, subpopulation interactions and gene fusions. Additionally, cancer stem cells (CSCs) have been verified to be involved in drug resistance utilizing organoid technology. Reversal of drug resistance can be achieved by targeting key genes and CSCs in cancer organoids. In this review, we summarize applications of organoids to cancer drug resistance research, indicating prospects and limitations.

Huan Tang, Wenjuan Di, Hanmei Qi, Juan Liu, Jing Yu, Jinmei Cai, Bing Lai, Guoxian Ding, Peng Cheng Department of Gerontology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Peng Cheng, Department of Gerontology, The First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing, 210029, Jiangsu, People’s Republic of China, Tel +86-25-68305171, Fax +86-25-83724440, Email cphh@sohu.comPurpose: This study was designed to explore age-related changes in trabecular bone score (TBS) and bone mineral density (BMD) in Chinese men through cross-sectional and longitudinal studies.Patients and Methods: We included adult men who had at least twice TBS and BMD examinations in our hospital between January 2013 and December 2020. All men were divided into an age subgroup per 10 years, comparing differences in baseline lumbar spine (LS) TBS and BMD at various parts between each age group and analyzing age-related changes in TBS and BMD during follow-up.Results: Baseline data showed that in men aged 36 to 85 years, BMD in the hip region showed a decreasing trend with age (P for trend < 0.01). However, TBS reached a high value around the age of 50, after which it decreased with age (P for trend = 0.03). During a mean follow-up of 3 years, the average annual change rate at TBS was − 0.17% in men aged 36 to 85 years, with the fastest decrease rate − 1.08% at 66 to 75 years (P < 0.05). The mean annual rate of change in LS BMD in different age subgroups increased with age (P for trend = 0.001). There was no significant decrease in mean annual change in BMD in hip regions.Conclusion: In men aged 36∼ 85 years, the trend of TBS was inconsistent with BMD. Men experience a high value of LS TBS around age 50, later than the commonly believed age of peak BMD, which may reflect developmental differences between bone microstructure and bone minerals. The TBS may be used as a better indicator of changes in bone strength than BMD in adult men at short-term follow-up. The rapid loss of TBS at age 66 to 75 may have implications for the prevention and medication of osteoporosis in men.Keywords: age-related, bone loss, bone mineral density, men, osteoporosis, trabecular bone score

To minimize environmental risks and the phytotoxic influence of organic materials on crop growth, it is necessary to test their phytotoxicity and maturity when they were used in farmland. However, the stress response of seed germination to chicken manure and cornstalks is not clear. This study used multi-omics analysis to investigate the inhibition mechanism of seed germination by chicken manure and cornstalk. Chicken manure caused destructive inhibition of seed germination with higher phytotoxicity (GI = 0). Cornstalk also had a low GI (8.81 %), while it mainly inhibited radicle growth (RL = 9.39 %) rather than seed germination (GR = 93.33 %). The response of radish seed germination to chicken manure and cornstalk phytotoxic stresses was accompanied by metabolic adjustments of storage substance accumulation, antioxidant enzyme activity change, phytohormone induction, and expression of specific proteins and gene regulation. Combined transcriptomic and proteomic analysis revealed that differential expression of 13,090 (5944 upregulated/7146 downregulated) and 3850 (2389 upregulated/1461 downregulated) genes (DEGs), and 1041 (82 upregulated/932 downregulated) and 575 (111 upregulated/464 downregulated) proteins (DEPs) at chicken manure and cornstalk treatment, respectively. Most down-regulated genes and proteins were involved in phenylpropanoid biosynthesis under chicken manure stress, which caused irreversible inhibition of seed germination. Down-regulation of phytohormone signal transduction-related genes under cornstalk stress resulted in inhibition of radicle growth, but the inhibitory stress was restorable. These findings provide new insight into the phytotoxicity of livestock manure and cornstalk on seed germination.

Aristolochic acid (AA), mainly derived from herbal

The molecular process of biological aging might be accompanied by significant metabolic derangement, especially in the central nervous system (CNS), since the brain has an enormous energy demand. However, the metabolic signature of the aging process in cerebrospinal fluid (CSF) has not been thoroughly investigated, especially in the Asian population. In this prospective cohort study on CSF metabolomics using proton nuclear magnetic resonance (NMR) spectroscopy, fasting CSF samples from 75 cognitively unimpaired patients aged 20-92 years without diabetes or obesity, undergoing spinal anesthesia for elective surgery were analyzed. Several metabolites in CSF samples were identified as having a significant association with the aging process in cerebral circulation; among the metabolites, the levels of alanine, citrate, creatinine, lactate, leucine, tyrosine, and valine significantly increased in old patients compared to those in young patients. The combined CSF metabolite alterations in citrate, lactate, leucine, tyrosine, and valine had a superior correlation with the aging process in all age groups. In conclusion, our pilot study of aging CSF metabolomics in the Taiwanese population presents significantly altered CSF metabolites with potential relevance to the aging process. These metabolic alterations in CSF samples might imply increasing anaerobic glycolysis, mitochondrial dysfunction, and decreasing glucose utilization in cerebral circulation in aged patients.

Purpose:The study aimed to investigate left ventricular (LV) motion pattern in patients with LBBB patterns including patients with pacemaker rhythm (PM), type B Wolff-Parkinson-White syndrome (B-WPW), premature ventricular complexes originating from the right ventricular outflow tract (RVOT-PVC), and complete left bundle branch block (CLBBB).Methods: Two-dimensional speckle tracking was used to evaluate peak value and time to peak value of the LV twist, LV apex rotation, and LV base rotation in patients with PM, B-WPW, RVOT-PVC, and CLBBB with normal LV ejection fraction, and in age-matched control subjects.Results: The LV motion patterns were altered in all patients compared to the control groups. Patients with PM and CLBBB had a similar LV motion pattern with a reduced peak value of LV apex rotation and LV twist. Patients with B-WPW demonstrated the opposite trend in the reduction of LV rotation peak value, which was more dominant in the basal layer. The most impairment in the LV twist/rotation peak value was identified in patients with RVOT-PVC. Compared to the control group, the apical-basal rotation delay was prolonged in patients with CLBBB, followed by those with B-WPW, RVAP, and RVOT-PVC.Conclusion: The LV motion patterns were different among patients with different patterns of LBBB. CLBBB and PM demonstrated a reduction in LV twist/rotation that was pronounced in the apical layer, B-WPW showed a reduction in the basal layer, and RVOT-PVC in both layers. CLBBB had the most pronounced LV apical-basal rotation dyssynchrony.

The curved photonic nanojet (CPNJ) produced due to the interaction between a dielectric circular cylinder rotating at a stable angular velocity and a plane wave is investigated. Based on this model, the optical Magnus effect of a dielectric circular cylinder is verified. And the analytical expression of both internal and external electric field are given based on the instantaneous rest-frame theory and the partial-wave series expansion method in cylindrical coordinates. The influence of the size parameter, the relative refractive index, and the rotating dimensionless parameter on the CPNJ are analyzed and discussed in numerical results. The "photonic nanojet curved" effect is highlighted, which can be used to generate the off-axis photonic nanojet (PNJ) controlling particles by adjusting the angular velocity of the dielectric cylinder. The results of this manuscript have promising application prospects in optical tweezers, particle manipulation, and optical trapping. Moreover, it also provides theoretical support for the particle spinning and generation of the off-axis CPNJ.

Asian Gelsemium elegans (G. elegans) has a wide range of pharmacological activities. However, its strong toxicity limits its potential development and application. Interestingly, there are significant gender differences in G. elegans toxicity in rats. This work aimed to elucidate the overall absorption, distribution, metabolism, and excretion (ADME) of whole G. elegans crude extract in female and male rats using high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC/QqTOF-MS), which facilitates determining the reasons for the gender differences in toxicity. A total of 25 absorbed bioactive components and 3 related produced metabolites were tentatively identified in female rats, while only 17 absorbed bioactive components and 3 related produced metabolites were identified in male rats. By comparison of peak intensities, most compounds were found to be more active in absorption, distribution and excretion in female rats than in male rats, which showed that female rats were more sensitive to G. elegans. This study was the first to investigate the multicomponent in vivo process of G. elegans in rats and compare the differences between sexes. It was hypothesized that differences in the absorption of gelsedine-type alkaloids were one of the main reasons for the sex differences in G. elegans toxicity.

Given the possible ecological dangers of graphene oxide (GO), a thorough understanding of its aggregation behavior is essential. During industrial applications, GOs may be used as multi-layered, and there is some possibility that GOs are released into the water environment in the aggregated state. Thus, elucidating the fate of aggregated GO is valuable for evaluating their environmental fate. In this work, the effect of pH on the fate of aggregated graphene oxide (GO) was explored using experimental measurements and molecular dynamic simulations and promoted aggregation of GO upon the increase of pH was observed. Additional investigations show that the presence of oxidation debris (ODs) on GO served as the primary driver of the unanticipated trend in aggregation behavior. GO consists of lightly oxidized functionalized graphene sheets and highly oxidized ODs. Upon the increase of pH and the deprotonation of functional groups, ODs are stripped from GO due to electrostatic repulsions and steric hindrance of water molecules. The stripping of ODs decreased the zeta potential and increased the hydrophobicity of GO, thus accelerating the aggregation. Additionally, the stripped ODs may recombine to GO edges and bridged GOs, which also contribute to further aggregation. Functional group deprotonation, ODs stripping, OD bridging, double layer compression, and charge neutralization all worked together to promote aggregation, resulting in the formation of FG-water-OD aggregates. Overall, the presence of ODs complicates the structures and properties of GO and should be considered during the development of GO-related nanomaterials and the evaluation of their environmental impact.

Sepsis is a systemic inflammatory response syndrome with high mortality and morbidity worldwide. In this study, we demonstrate that capsaicin not only suppresses inflammation in lipopolysaccharide (LPS)-induced macrophages, but also effectively inhibits endotoxemia or sepsis-related inflammation in vivo. We have designed and synthesized a series of capsaicin-based probes, which permit the profiling of the target proteins of capsaicin using activity-based protein profiling (ABPP). Among the identified protein targets, we discover that capsaicin directly binds to and inhibits PKM2 and LDHA, and further suppresses the Warburg effect in inflammatory macrophages. Moreover, capsaicin targets COX-2 and downregulates its expression in vivo and in vitro. Taken together, the present findings indicate that capsaicin alleviates the inflammation response and the Warburg effect in a TRPV1-independent manner by targeting PKM2-LDHA and COX-2 in sepsis. Thus, capsaicin may function as a novel agent for sepsis and inflammation treatment.

There are rarely new therapeutic breakthroughs present for neurodegenerative diseases in the last decades. Thus, new effective drugs are urgently needed for millions of patients with neurodegenerative diseases. Celastrol, a pentacyclic triterpenoid compound, is one of the main active ingredients isolated from

Background Chemotherapy is still the main first-line treatment for advanced metastatic gastric cancer, but it has the limitations of serious side effects and drug resistance. Conventional liposome has been substantially used as drug carriers, but they lack targeting character with lower drug bioavailability in tumor tissues. Based on the above problems, a novel estrogen-targeted PEGylated liposome loaded with oxaliplatin (ES-SSL-OXA) was prepared to further improve the metabolic behavior, the safety profile, and the anti-tumor efficacy of oxaliplatin. Methods Four kinds of oxaliplatin (OXA) liposomes were prepared by film hydration method. The obtained formulations were characterized in terms of entrapment efficiency (EE), particle size, and so on by HPLC and DLS (dynamic light scanning). The morphology of ES-SSL-OXA was detected by transmission electron microscope (TEM). The in vitro and in vivo targeting effect of ES-SSL-OXA was verified by fluorescence microscopy and in vivo imaging system in gastric cancer cells (SGC-7901) and tumor-bearing athymic mice. The in vitro and in vivo antitumor efficacies of ES-SSL-OXA were investigated on SGC-7901 cells and athymic tumor-bearing mice. Pharmacokinetic, biodistribution, and acute toxicity tests of ES-SSL-OXA were performed on ICR mice. Results The ES-SSL-OXA exhibited an average particle size of about 153.37 nm with an encapsulation efficiency of 46.20% and low leakage rates at 4°C and 25°C. In vivo and in vitro targeting study confirmed that ES-SSL-OXA could effectively target the tumor site. The antitumor activity demonstrated the strongest inhibition in tumor growth of ES-SSL-OXA. Pharmacokinetics and acute toxicity study showed that ES-SSL-OXA could significantly improve the metabolic behavior and toxicity profile of oxaliplatin. Conclusion In this study, a novel estrogen-targeted long-acting liposomal formulation of OXA was successfully prepared. ES fragment effectively targeted the delivery system to tumor tissues which highly express estrogen receptor, providing a promising therapeutic method for gastric cancer in clinic., Graphical Abstract

Canine babesiosis is a serious disease among tick-borne haemoprotozoan diseases that threaten dog health. To find out the prevalence of canine babesiosis and its main pathogenic species in Shaanxi Province, the study was centered on the infection of babesiosis in dogs in different regions of the Province. First, a total of 367 blood samples were collected in Shaanxi Province, and 53 Babesia nucleic-acid-positive samples were found by polymerase chain reaction (PCR) identification, with a positive rate of 14.44%, and Babesia gibsoni was found by sequencing analysis. Further analysis showed that the prevalence of canine babesiosis was significantly different in 5 regions. There was no significant difference in infection rates between age groups, with the lowest prevalence in young dogs (10.81%) and the highest in adult dogs (17.29%). The infection rate in male dogs was higher than in female dogs. The morbidity of canine Babesia spp. was significantly different between different seasons, with the highest infection rate in autumn (27.78%) and the lowest in winter (6.10%). In conclusion, the epidemicity of canine Babesia spp. in dogs was mainly affected by region and season, and B. gibsoni was the most common canine Babesia spp. within Shaanxi Province in our study. These results provide basic data for the prevention and control of canine babesiosis in this region.

Information asymmetries are known in theory to lead to inefficiently low credit provision, yet empirical estimates of the resulting welfare losses are scarce. This paper leverages a randomized experiment conducted by a large fintech lender to estimate welfare losses arising from asymmetric information in the market for online consumer credit. Building on methods from the insurance literature, we show how exogenous variation in interest rates can be used to estimate borrower demand and lender cost curves and recover implied welfare losses. While asymmetric information generates large equilibrium price distortions, we find only small overall welfare losses, particularly for high-credit-score borrowers. Institutional subscribers to the NBER working paper series, and residents of developing countries may download this paper without additional charge at www.nber.org.

High fat diet induced hyperlipidemia hamster model was used to explore the anti-hyperlipidemia effect of water extract of Moringa oleifera leaves( WEMOL). On this basis,the possible action mechanism was predicted by network pharmacology. Golden hamsters were randomly divided into normal diet group( NFD),high-fat diet group( HFD),simvastatin group,high dose group of WEMOL( HIWEMOL) and low dose group of WEMOL( LOWEMOL). The model was administered simultaneously for 66 days,during which the body weight changes of hamsters were recorded. At the end of the experiment,serum lipid level and serum transaminase level of golden hamsters in each group were detected,and the pathological changes of liver were observed by hematoxylin-eosin( HE) staining. The results showed that WEMOL could significantly decrease the serum total cholesterol( TC),total triglyceride( TG),low density lipoprotein cholesterol( LDL-c) levels,and reduce the lipid deposition in liver tissue,thus improving the hyperlipidemia of golden hamsters. According to the prediction of network pharmacology,219 targets of potential active components of M.oleifera leaves and 185 targets of water-soluble potential active components of M. oleifera leaves for the treatment of hyperlipidemia were obtained separately. The MCODE analysis was performed on the PPI network of 219 targets and 185 targets obtained above and got five and four clusters respectively. The signaling pathway analysis of clusters showed that among the common pathways,nonalcoholic fatty liver,insulin resistance,MAPK signaling pathway,estrogen signaling pathway,cell apoptosis and HIF-1 signaling pathway were associated with hyperlipidemia. In addition,the potential active components of M. oleifera leaves could also inhibit the metabolic inflammation of hyperlipidemia by modulating complement and coagulation cascades signaling pathway,and GSK3 B,F2,AKT1,RELA,SERPINE1 might be the key targets. The water-soluble potential active components of M. oliefera leaves could modulate lipid metabolism by modulating AMPK signaling pathway and JAK-STAT signaling pathway,with PIK3 CB,PIK3 CA,CASP3,AKT1 and BCL2 as the key targets. These results suggested that WEMOL had anti hyperlipidemia effect,and its mechanism might be related to the protein expression regulation of lipid metabolism,nonalcoholic fatty liver disease and atherosclerosis related signaling pathways.

In this work, the aggregation mode of graphene oxide (GO) was identified. Atomic force microscopy (AFM) characterization indicated that protonation at lower pH was more efficient in accelerating the stacking of GO than binding with metal ions, and molecular dynamics (MD) simulations revealed that this should be attributed to the different favorable aggregation modes under different aqueous chemistries. GO tended to aggregate in the face-to-face or partial face-to-face mode at lower pH, and in the partial face-to-face, edge-to-edge, or point-to-point mode at higher pH with the presence of metal ions. To elucidate the mechanisms where pH and metal ions can exert distinct effects on the aggregation mode of GO, density functional theory calculations were performed. The results demonstrated that the favorable face-to-face and partial face-to-face aggregation at lower pH was mainly guided by the stronger π–π interaction and suppressed water-mediated steric hindrance; however, hydrogen bond and vdW interactions were not important in determining the aggregation mode. Overall, the distinct aggregation mode of GO under different aqueous chemistries will shed light on predicting the toxicity and environmental applications of GO.

Background Breast cancer is the leading cause of cancer death in women. Chemotherapy to inhibit the proliferation of cancer cells is considered to be the most important therapeutic strategy. The development of long-circulating PEG and targeting liposomes is a major advance in drug delivery. However, the techniques used in liposome preparation mainly involve conventional liposomes, which have a short half-life, high concentrations in the liver and spleen reticuloendothelial system, and no active targeting.

In this paper, a low-cost hardware architecture of the bilateral filter for real-time image processing is proposed. Based on the techniques of distance-oriented grouping and hardware resource sharing, the usage of multipliers can decrease 48% as compared to the previous approach. Besides, an efficient quantization method is applied to reduce the size of required look up tables. The experimental results show that the proposed architecture is cost efficient while maintaining the same image quality, frame rate and working clock frequency.

Purpose. Lung cancer has been the top-ranking cause of cancer deaths in Taiwan for decades. Limited data were available in global cancer surveillance regarding lung cancer epidemiology in Taiwan, and previous reports are outdated. Patients and Methods. This population-based cohort study extracted data of patients with lung cancer from the Taiwan National Health Insurance database and determined the lung cancer incidence and prevalence during 2002–2014. Histological subtypes were retrieved from the Taiwan Cancer Registry database; survival rates were gathered from the National Death Registry. Average annual percentage changes (APCs) of prevalence, incidence, and overall survival were estimated by joinpoint regression analysis. Results. Age-standardized incidence of lung cancer increased from 45.04 per 100,000 person-years in 2002 to 49.86 per 100,000 person-years in 2014, with an average APC of 0.7 (95% CI = 0.3–1.1; 0.2 in males, 2.0 in females). Lung cancer was more prevalent in male patients, but this increase gradually slowed down. Socioeconomic analysis showed that lung cancer has higher prevalence in patients with higher income level and urban residency. Adenocarcinoma was the most abundant histological subtype in Taiwan (adenocarcinoma-to-squamous cell carcinoma ratio = 4.16 in 2014), with a 2.4-fold increase of incident cases during 2002–2014 (from 43.47% to 64.89% of all lung cancer cases). The 5-year survival rate of lung cancer patients in 2010 was 17.34% (12.60% in male, 25.40% in female), with an average APC of 9.3 (6.3 in male, 11.8 in female) during 2002–2010. Conclusion. Average APCs of prevalence and incidence of lung cancer were 3.1 and 0.7, respectively, during 2002–2014 in Taiwan. The number of female patients and number of patients with adenocarcinoma have increased the most, with incident cases doubling in these years. Facing this fatal malignancy, it is imperative to improve risk stratification, encourage early surveillance, and develop effective therapeutics for lung cancer patients in Taiwan.

CoCrPt material is used for perpendicular magnetic recording media due to its high magneto-crystalline anisotropy that brings good thermal stability on the media. The addition of SiO2 between the CoCrPt grains offers benefits including lower noise and better thermal stability. It has been reported that the SiO2 content has strong effects on the media’s recording performance such as coercivity, anisotropy and noise. In this work, we focus on studying the effects of the SiO2 content on the nanomechanical properties of the media which are critical for the head-disk interface reliability. Variations of these properties with SiO2 content provide guidelines for optimum designs considering both recording and mechanical interface performance.

Media lubricants are critical to the reliability of hard disc drives (HDDs). Ideally, the lubricant should have high thermal stability and low monolayer (ML) thickness. Unfortunately, the state-of-...

In order to understand the significant differences in activities and effects between Asian ginseng (ASG) and American ginseng (AMG), it is important to study the correlation between chemical struct...

The adsorption characteristics and mechanisms of ionic organic compounds dependent on their dissociation species are still unclear, which hindered the understanding of their environmental behavior and risks. This study compared the sorption of four bisphenol compounds (BCs) on graphite adsorbents, with a specific emphasis on the roles of charge assisted hydrogen bond (CAHB). The negative correlations between the localized orbital locator integrated π over plane index and the single point adsorption coefficient Kd of the four BCs indicated that π–π interaction was an important mechanism for BCs adsorption on graphite adsorbents. Based on the speciation distribution calculation and the modeling of pH-dependent adsorption, the apparent adsorption coefficient of different species were obtained. Except for bisphenol S, the KdHA− of BC monovalent anions was 2.6 times to one order magnitude higher than that of the neutral species. According to the density functional theory (DFT) calculation, strong CAHB is expected between BC monovalent anions and graphite adsorbents, indicating that CAHB overcame the enhanced electrostatic repulsion and became the dominant adsorption mechanism. This study highlighted the importance of CAHB in the adsorption of ionic organic compounds on carbonaceous materials, which should be carefully taken into consideration for their environmental fate studies.

Graphical abstract, Highlights • Six new natural compounds were isolated from Millettia pachyloba Drake. • The cytotoxic activities of these new compounds were evaluated. • Ten (3–5, 9, 12, 17–19, 24, and 25) of 28 isolated compounds showed cytotoxicity. • The ten cytotoxic compounds induced autophagy in cancer cells. • Compound 9 induced apoptosis and autophagy, suggesting it could be a potential anticancer drug candidate., In this study, systematic separation and subsequent pharmacological activity studies were carried out to identify cytotoxic natural products from the dried stems of Millettia pachyloba Drake. Five previously undescribed isoflavones, pachyvones A–E; one previously undescribed xanthone, pachythone A; and twenty-two known compounds were obtained. The structures of these compounds were assigned on the basis of 1D/2D NMR data and high-resolution electrospray ionization mass spectroscopy analysis. Preliminary activity screening with HeLa and MCF-7 cells showed that ten compounds (3–5, 9, 12, 17–19, 24, and 25) had potential cytotoxicity. Further in-depth activity studies with five cancer cell lines (HeLa, HepG2, MCF-7, Hct116, and MDA-MB-231) and one normal cell line (HUVEC) revealed that these ten compounds showed specific cytotoxicity in cancer cells, with IC50 values ranging from 5 to 40 μM, while they had no effect on normal cell lines. To investigate whether the cytotoxicity of these ten compounds was associated with autophagy, their autophagic effects were evaluated in GFP-LC3-HeLa cells. The results demonstrated that compound 9 (durmillone) significantly induced autophagy in a concentration-dependent manner and had the best activity as an autophagy inducer among all of the compounds. Therefore, compound 9 was selected for further study. The PI/Annexin V double staining assay and Western blotting results revealed that compound 9 also induced obvious apoptosis in HeLa and MCF-7 cells, which suggests that it mediates cytotoxic activity through activation of both apoptosis and autophagy. Taken together, this study identified ten natural cytotoxic products from the dried stems of Millettia pachyloba Drake, of which compound 9 induced apoptosis and autophagy and could be an anticancer drug candidate.