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Vein thrombosis is one of the most serious types of cardiovascular disease. During the traditional treatment, due to the excessive blood flow rate, the drug utilization rate at the thrombus site is low and the thrombolysis efficiency is poor. In this study, bowl-shaped silica nanomotors driven by nitric oxide (NO) are designed to target the thrombus surface by modifying arginine-glycine-aspartic acid (RGD) polypeptide, and simultaneously loading l-arginine (LA) and thrombolytic drug urokinase (UK) in its mesopore structure. LA can react with excessive reactive oxygen species (ROS) in the thrombus microenvironment to produce NO, thus promoting the movement of nanomotors to improve the retention efficiency and utilization rate of drugs in the thrombus site, and at the same time achieve the effect of eliminating ROS and reducing the oxidative stress of inflammatory endothelial cells. The loaded UK can dissolve thrombus quickly. It is worth mentioning that NO can not only be used as a power source of nanomotors, but also can be used as a therapeutic agent to stimulate the growth of endothelial cells and reduce vascular injury. This therapeutic agent based on nanomotor technology is expected to provide support for future research on thrombus treatment.

Inducing autophagy of macrophages to improve abnormal lipid metabolism is an important way to treat atherosclerosis (AS). Yet, the current application of the mammalian target of rapamycin (mTOR)-dependent autophagy inducers is limited by the side effects and lack of targeting and low biological availability. Herein, a kind of nitric oxide (NO)-driven carrier-free nanomotor based on the reaction between trehalose (Tr, one of the mTOR-independent autophagy inducers)

Above 50% of deaths can be attributed to chronic inflammatory diseases; thus, the construction of drug delivery systems based on effective interaction of inflammatory factors with chemotactic nanoparticles is meaningful. Herein, a zwitterion-based artificial chemotactic nanomotor is proposed for universal precise targeting strategy in vivo, where the high level of reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) in inflammatory sites are used as a chemoattractant. Multidimensional static models, dynamic models, and in vivo models are established to evaluate chemotactic performance. The results show that the upregulated ROS and iNOS can induce the chemotaxis of nanomotors to diseased tissues in inflammation-related disease models. Further, mesoscale hydrodynamics simulations are performed to explain the chemotactic behavior of the nanomotors. Such a chemotactic delivery strategy is expected to improve delivery efficiency and may be applicable to a variety of inflammatory diseases.

The ability of nanomotors to promote the deep penetration of themselves and the loaded drugs in diseased tissues has been proposed and confirmed. However, whether such motion behavior of the nanomotors can also promote deep penetration of micrometer-sized immune cells in the diseased microenvironment, which is important for the immunotherapy of some diseases, has not been mentioned. Herein, we construct a nitric oxide (NO)-driven nanomotor that can move in the tumor microenvironment, focusing on its motion behavior and the role of NO, the beneficial product released during movement from this kind of nanomotor, in regulating the infiltration behavior and activity of immune cells. It can be found that the drug-loaded nanomotors with both NO-releasing ability and motility can promote the normalization of the tumor vasculature system and the degradation of the intrinsic extracellular matrix (ECM), which can significantly improve the tumor infiltration ability of T cells in vivo. The efficiency of T-cell infiltration in tumor tissue in vivo increased from 2.1 to 28.2%. Both subcutaneous and intraperitoneal implantation tumor models can validate the excellent antitumor effect of drug-loaded NO-driven nanomotors. This combination of motility of the power source from nanomotors and their physiological function offers a design idea for therapeutic agents for the future immunotherapy of many diseases.

One of the difficulties in atherosclerosis treatment is that the ablation of inflammatory macrophages, repair of vascular endothelial injury, and anti-tissue proliferation should be considered. However, there are few studies that can solve the abovementioned problems simultaneously. Herein, we present a kind of near-infrared (NIR) light-driven multifunctional mesoporous/macroporous tubular micromotor which can rapidly target the damaged blood vessels and release different drugs. Their motion effect can promote themselves to penetrate into the plaque site, and the generated heat effect caused by NIR irradiation can realize the photothermal ablation of inflammatory macrophages. Furthermore, these micromotors can rapidly release the vascular endothelial growth factor for endothelialization and slowly release paclitaxel for antiproliferation to achieve synergistic treatment of atherosclerosis. In vivo results demonstrated that the micromotors can achieve a good therapeutic effect for atherosclerosis. This kind of micro/nanomotor technology with a complex porous structure for drug loading will bring a more potential treatment platform for the disease.

Destruction of tumor metabolism symbiosis is an attractive cancer treatment method which targets tumor cells with little harm to normal cells. Yet, a single intervention strategy and poor penetration of the drug in tumor tissue result in limited effect. Herein, we propose a zero-waste zwitterion-based hydrogen sulfide (H 2 S)-driven nanomotor based on the basic principle of reaction in human body. When loaded with monocarboxylic acid transporter inhibitor α-cyano-4-hydroxycinnamic acid (α-CHCA), the nanomotor can move in tumor microenvironment and induce multiple acidosis of tumor cells and inhibit tumor growth through the synergistic effect of motion effect, driving force H 2 S and α-CHCA. Given the good biosafety of the substrate and driving gas of this kind of nanomotor, as well as the limited variety of nanomotors currently available to move in the tumor microenvironment, this kind of nanomotor may provide a competitive candidate for the active drug delivery system of cancer treatment.

Hypersampones A-C (

It is of great significance to find effective thrombolytic treatments due to the harm caused by thrombosis to human health. Based on the formation mechanism and complex microenvironment of a thrombus, polydopamine nanomotors (PDANMs) modified by the peptide of Arg-Gly-Asp (RGD) and loaded with urokinase (UK) were designed and prepared. A polydopamine (PDA) substrate has a good photothermal conversion effect. Under near-infrared (NIR) light irradiation, it can not only perform photothermal therapy (PTT) on thrombus, but also provide the driving force of PDANMs. Thrombolytic drug UK was loaded in the mesoporous structure of the PDA substrate and can be released at the thrombus site for drug therapy. The modified RGD can target the thrombus site, moreover, benefiting from the guanidine group of L-arginine in the peptide chain, and RGD can interact with reactive oxygen species (ROS) in the thrombus microenvironment to produce nitric oxide (NO). NO not only propelled the movement of nanomotors, but also promoted the growth of vascular endothelial cells to repair damaged blood vessels. The experimental results show that NIR and NO can provide dual driving sources for the nanosystem to achieve continuous and deep penetration of the drug-loaded nanomotors at the thrombus site, while realizing the photothermal and drug synergistic therapy to enhance the therapeutic effect and promote the growth of vascular endothelium cells. This kind of thrombus treatment strategy based on nanomotor drug delivery systems will provide good technical support for the clinical treatment of inferior vena cava thrombus.

Micro/nanomotors bring new possibilities for the detection and therapy of diseases related to the blood environment with their unique motion effect. This work reviews the research progress of using micro/nanomotors in the detection and therapy of diseases related to the blood environment. First, we outline the advantages of using micro/nanomotors in blood-related disease detection. To be specific, the motion capability of micro/nanomotors can increase plasma or blood fluid convection and accelerate the interaction between the sample and the capture probe. This allows the effective reduction of the amount of reagents and treatment steps. Therefore, the application of micro/nanomotors significantly improves the analytical performance. Second, we discuss the key challenges and future prospects of micro/nanomotors in the treatment of blood-environment related diseases. It is very important to design a unique treatment plan according to the etiology and specific microenvironment of the disease. The next generation of micro/nanomotors is expected to bring exciting progress to the detection and therapy of blood-environment related diseases.

Current exosome engineering methods usually lead to the damage of exosome morphology and membrane, which cannot meet the complex needs of disease treatment. Herein, the concept of an "independent module/cascading function" is proposed to construct an engineered exosome nanotherapy platform including an independent artificial module and a natural module. The artificial module with movement/chemotaxis function is first synthesized, and then it is controllably combined with the natural exosome module with "one by one" mode through a "differentiated" modification method. The whole process can not only maintain the activity of the natural exosome module, but also endows it with motion ability, so as to realize the purpose of "cascading function" in the process of disease treatment. The above engineered exosomes are used in the treatment of Parkinson's disease (PD). Moreover, the multistep targeting strategy of "disease microenvironment-damaged cells-diseased mitochondria" and the multistage intervention concept of "inhibiting deterioration and promoting repair" are proposed, so as to break through the bottleneck of the existing treatment of PD.

Although a large number of endometrial cancer patients are cured with surgery alone, there are significant numbers of patients with more aggressive variants of endometrial carcinoma for whom the prognosis remains poor. We investigated the effects of prevalence, histotypes, and immunohistochemical profiles on prognostic value in a hospital-based population.A retrospective study of surgically resected primary endometrial carcinoma was included. Immunohistochemical stains were performed on formalin-fixed paraffin-embedded tissue microarray sections for β-Catenin, estrogen receptor (ER), progesterone receptor (PR), HER-2, MLH1, MSH2, MSH6, PMS2, and p53.Loss of mismatch repair expression was detected in 25.4% of samples (29/114, mean age 57 years) of the tumors. The following loss of expression was observed in patients: MLH1/PMS2 in 16.6% of patients, MSH6 in 7.0% of patients, MLH1 in 0.9% of patients, and MSH6/PMS2/MLH1 in 0.9% of patients. Immunohistochemistry of p53 was analyzed for 111 patients. A total of 13 patients (11.7%, mean age 64 years) had p53-abnormal expression (absent, cytoplasmic or diffuse strong positive patterns), and more than half (9/13, 69.2%) had endometrioid histotype. Abnormalities in p53 were significantly associated with histotype (p = 0.001), advanced tumor stage (p = 0.038), death of disease (p = 0.002), PR percentage (p = 0.002), and HER-2 expression (p = 0.018). Immunohistochemical nuclear localization of β-Catenin was detected in 7.1% of the cohort. The combination of p53 and nuclear β-Catenin expressions was not significantly predictive of disease-free or overall survival.The results of this study are useful for management of endometrial cancer in patients with DNA mismatch repair, abnormal p53 expression, or nuclear localization of β-Catenin.

Nanomaterials have been widely used in cancer treatment and have achieved remarkable results. However, the specificity of the tumor microenvironment and a series of biological barriers (such as blood flow, cell membrane, dense tissue, etc.) have caused many obstacles faced by nanomaterials after entering the human body, which makes traditional drug delivery vehicles have insurmountable difficulties, such as low delivery efficiency, poor permeability, etc. The micro/nanomotors with autonomous movement capabilities provide the possibility to solve the above problems. Therefore, this review summarizes the current researches of micro/nanomotors strategies to overcome the different biological barriers of nanomaterials in cancer treatment. The advantages and disadvantages of three typical micro/nanomotors (biological, physical and chemical micro/nanomotors) in cancer treatment are summarized separately, and the future design of micro/nanomotors more suitable for tumor environment was discussed.

Zhibai Dihuang pill (ZBDH), a Chinese herbal formula, has been widely used as an adjunctive therapy to help reduce the patient's steroid dose and maintain low disease activity in systemic lupus erythematosus (SLE).This systematic review evaluates the therapeutic effect of modified ZBDH in reducing steroid use in patients with SLE.A systematic literature search was carried out using seven databases, including PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, Chinese VIP Information and Wanfang Database, from their inception to June 1st, 2019. The search terms included "systemic lupus erythematosus," "Chinese medicine" and "clinical trial," and their synonyms. Subject headings matching the above terms were also used.This meta-analysis included randomized controlled trials that evaluated the reduction of steroid dose in patients with SLE. Traditional Chinese medicine (TCM) formulas in experimental group should be prescribed based on ZBDH and used as adjunctive therapy and the comparator should contain steroids.Two authors independently conducted database search, study selection, data extraction and quality assessment. The extracted information contained study design, sample size, recruitment mode, diagnostic criteria, inclusion and exclusion criteria, participant characteristics, TCM patterns, TCM formulas and treatment outcomes. The primary outcome was the change of steroid dose. Secondary outcomes included SLE Disease Activity Index (SLEDAI), biomarkers of disease activity and clinical response rate. STATA 15.0 was used to analyze the pooled effects reported as weighted mean difference (WMD) or odds ratio, with a 95% confidence interval (CI).In total, 20 trials involving 1470 SLE patients were included. The pooled result showed that modified ZBDH taken in combination with standard care led to a larger reduction in steroid dose, compared to standard care alone (WMD: 3.79; 95% CI: 2.58-5.01; P 0.001). Favorable outcomes were also seen in secondary outcome criteria, such as SLEDAI and complement 3. The modified ZBDH treatments were well tolerated without increasing adverse effects.The systematic review provided preliminary evidence supporting the use of ZBDH as a co-therapy to aid steroid dose reduction in patients with SLE. However, more rigorous studies should be conducted to validate these findings, and explore the mechanisms of ZBDH's relevant bioactive constituents.

The goal of this study is to develop and validate a novel semi-automatic detection method (SADM) under nasopharyngoscopy based on the image processing technique, which can assist the evaluation of the velar closure ratio (VCR). After the development of the SADM, 72 patients were enrolled. The reliability of SADM was evaluated by repeated measurements. Velar closure ratio are given by conventional nasopharyngoscopy method and SADM were compared. Velar closure ratios given by SADM were further translated into a trichotomous classification for velopharyngeal function diagnosis, that is, velopharyngeal closure (VPC), marginal VPC (MVPC), and velopharyngeal incomplete. The 2 VCR-thresholds used for the translation were explored and validated. As results shown, SADM was proved to be reliable with an intraclass correlation coefficient of 0.996 (95% confidence interval: 0.993-0.997, P 0.001). Intraclass correlation coefficient between conventional nasopharyngoscopy method and SADM was 0.954 (95% confidence interval: 0.927- 0.971, P 0.001). Velar closure ratio-thresholds were set at 0.82 and 0.92 according to the ROC curve. Diagnostic sensitivity and specificity for velopharyngeal incomplete were 1.00 and 1.00. MVPC had 0.58 sensitivity and 0.96 specificities while VPC had 0.92 and 0.79, respectively. No statistically significant difference was found between the diagnosis of SADM and speech pathologists (P 0.1). In conclusion, this study successfully developed an accurate and reliable semi-automatic method to evaluate VCR, which could help improve the efficacy of VCR evaluation and velopharyngeal function diagnosis.

It is of great significance to develop micro/nanomotors with good biosafety and high efficiency for biomedical detection. In order to enhance the contact chances between the biosensors and the analytes in the complex blood sample, we report a near-infrared light (NIR)-driven fluorescent nanomotor, which can safely and efficiently capture and detect circulating tumor cells (CTCs) in the whole blood environment without pretreating procedures. Firstly, the structure of the fluorescent nanomotor was characterized and its motion behavior in different environments was analyzed. Subsequently, CTCs detection conditions were optimized to explore the effect of nanoscale autonomous mixing provided by nanomotor's motion behavior on the efficiency of CTCs capture. The results showed that the NIR-driven fluorescent nanomotor can keep moving in the complex biological medium so as to increase their contact chances with CTCs and improve the binding efficiency with the target analyte (the capture efficiency increased from 67.5% - 85% (no NIR irradiation) to 93.75-98.75% (under NIR irradiation)). Finally, due to the excellent fluorescence properties of the nanomotors, they can be applied to the visual detection of the whole blood samples obtained from clinical cancer patients. The NIR-driven nanomotor designed in this paper can detect CTCs in whole blood environment, which is a beneficial extension of the existing cell detection system of most micro/nanomotors in water phase environment.

Life does not sustain without water. For water, there is a natural abundance of stable isotope hydrogen and oxygen. Water molecules get across cell membranes through a plasma membrane protein, named aquaporin. Moreover, the kidney is the main organ to maintain water homeostasis. Here, we study the stable isotopic ratios of hydrogen and oxygen in human blood plasma and erythrocyte corresponding to kidney functions. We extract waters from human plasma and erythrocyte, collected from 110 participants, including 51 clinically stable outpatients with end-stage renal disease (ESRD) and 59 subjects with normal renal function (NRF). We observed that (i) both extracellular (blood plasma) and intracellular (erythrocyte) biology waters are isotopic differences between the ESRD and NRF participants, (ii) the natural abundance of isotopic waters of ESRD is hypo-isotopic, and (iii) the isotopic enrichment of water between erythrocyte and blood plasma are distinct. In addition, we introduce an empirical formula using entropy transformation to describe isotopic water enrichment for biology. Accordingly, the natural abundance of stable isotope water of blood plasma and erythrocyte may be possibly put in practice a new sign for assessments of kidney dysfunctions.

Limited tumor permeability of therapeutic agents is a great challenge faced by current cancer therapy methods. Herein, a kind of near infrared light (NIR)-driven nanomotor with autonomous movement, targeted ability, hierarchical porous structure, multi-drugs for cancer chemo/photothermal therapy is designed, prepared and characterized. Further, we establish a method to study the interaction between nanomotors and cells, along with their tumor permeability mechanism, including 2D cellular models, 3D multicellular tumor spheroids and in vivo models. In vivo tumor elimination results verify that the movement behaviour of the nanomotors can greatly facilitate them to eliminate tumor through multiple therapeutic methods. This work tries to establish systematic research and evaluation models, providing strategies to understand the relationship between motion behaviour and tumor permeation efficiency of nanomotors in depth.

Background Fournier's gangrene (FG), a urological emergency with high mortality, is an infectious necrotizing fasciitis of the perineal and genital regions. The majority of FG is caused by polymicrobial organisms involving mixed aerobes and anaerobes but rarely reveals Actinomyces species. Case presentation We report a healthy 67-year-old Asian male who presented with rapidly progressive painful swelling of the scrotum. Clinically diagnosed with FG, the patient underwent an emergency radical debridement, followed by broad-spectrum antibiotics and negative pressure wound therapy. The identification of the causative microorganisms showed Actinomyces turicensis and the antibiotic treatment was adjusted accordingly. After wound bed preparation, we took split-thickness skin grafts to cover the scrotal wound. Active management to minimize faecal contamination was applied throughout the whole course of treatment and repair. The patient was satisfied with the outcome. This was an extremely rare case of A. turicensis as the main causative pathogen of FG. Conclusions FG due to Actinomyces species is rarely reported, but we should still consider this pathogenic microorganism that has long been neglected.

Three new aglain derivatives (1-3), one known aglain derivative (4), two known rocaglamide derivatives (5 and 6), four known triterpenoids (7-10), and three steroids (11-13) were isolated from Aglaia odorata Lour. Their structures were established through the analysis of detailed spectroscopic data and electronic circular dichroism calculations. Five compounds (1 and 4-7) exhibited cytotoxic activities on human leukemia cells (HEL) and human breast cancer cells with IC

BackgroundThe association between sex and the survival of patients with esophageal cancer (EC) remains controversial. We sought to systematically investigate sex-based disparities in EC survival using the Surveillance, Epidemiology, and End Results (SEER) registry data from the United States.MethodsPatients with EC diagnosed from 2004 to 2015 registered in the SEER database were selected. The association between sex and cancer-specific survival (CSS) was evaluated using survival analysis. The Inverse Probability Weighting (IPW) approach was applied to reduce the observed bias between males and females. Subgroup analyses were used to investigate the robustness of the sex-based disparity and to explore potential interaction effects with other variables.ResultsOverall, 29,312 eligible EC patients were analyzed, of whom 5,781 were females, and 23,531 were males. Females had higher crude CSS compared to males (10-year CSS: 24.5 vs. 21.3%; P < 0.001). Similar results were obtained after adjusting for selection bias using the IPW approach and multivariate regression. Subgroup analyses confirmed the relative robustness of sex as a prognostic factor. However, significant interactions were observed between sex and other variables, such as age, race, tumor grade, histology, and treatment modality. In particular, there was no survival advantage for premenopausal females compared to their male counterparts, but the association between sex and EC survival was prominent in 46–55-year-old patients.ConclusionsFemale EC patients had better long-term survival than males. The association between sex and EC survival vary according to age, race, tumor grade, histology, and treatment modality. Sex-based disparity in EC-specific survival was age-related in the United States population.

Engineered platelets (PLT) can bring new possibilities for diseases treatment due to the specific response for a variety of physiological disease environments. However, the deep penetration of engineered PLT in diseased tissues such as tumor is still an important challenge that restricts the therapeutic effect. Herein, the engineered PLT micromotor (PLT@PDA-DOX) is constructed by a universal self-polymerization modification method of dopamine, and the chemotherapeutic drug doxorubicin (DOX) is loaded by both π-π stacking interaction with polydopamine (PDA) and cellular endocytosis of PLT. The experimental results prove that PLT@PDA-DOX can target to tumor site by the specific binding of PLT with cancer cells, and then the secondary PLT-derived microparticles (PMP@PDA-DOX) are released with the activation of PLT@PDA-DOX by tumor microenvironment (TME). Besides, benefiting from the photothermal conversion capability of PDA, PLT@PDA-DOX micromotors and PMP@PDA-DOX nanomotors are driven by near-infrared light to realize deep penetration. And the PLT-based micro/nanomotors with propulsion capability possess good performance for tumor ablating in vitro and in vivo. In consideration of the operability, mildness, universality of this modification method and the good biocompatibility of PDA, this work may provide a general paradigm for the construction of engineered cells in disease treatment.

The microneedle (MN) provides a promising strategy for transdermal delivery of exosomes (EXO), in which the therapeutic effects and clinical applications are greatly reduced by the fact that EXO can only partially reach the injury site by passive diffusion. Here, we designed a detachable MN array to deliver EXO modified by a nitric oxide nanomotor (EXO/MBA) for Achilles tendinopathy (AT) healing. With the releasing of EXO/MBA, l-arginine was converted to nitric oxide by NOS or ROS as the driving force. Benefiting from the motion ability and the property of MPC tending to lower pH, EXO could accumulate at the injury site more efficiently. This work demonstrated that EXO/MBA-loaded MN notably suppressed the inflammation of AT, facilitated the proliferation of tendon cells, increased the expression of Col1a, and prevented extracellular matrix degradation, indicating its potential value in enthesiopathy healing and other related biomedical fields.

Hydrogen sulfide (H

Background Takayasu arteritis (TAK) is a rare large vessel vasculitis, and epidemiological data on TAK are lacking in China. Thus, we designed this study to estimate the TAK prevalence and incidence in residential Shanghai, China. Methods Data on diagnosed TAK cases aged over 16 years were retrieved from 22 tertiary hospitals in Shanghai through hospital electronic medical record systems between January 1, 2015 and December 31, 2017 to estimate the prevalence and incidence. A systematic literature review based on searches in PubMed, Ovid-Medline, Excerpta Medica Database (EMBASE), Web of Science, and China National Knowledge Infrastructure (CNKI) was performed to summarize TAK distribution across the world. Results In total 102 TAK patients, with 64% female, were identified. The point prevalence (2015-2017) was 7.01 (95% CI 5.65-8.37) cases per million, and the mean annual incidence was 2.33 (1.97-3.21) cases per million. The average age of TAK patients was 44 ± 16 years, with the highest prevalence (11.59 [9.23-19.50] cases per million) and incidence (3.55 [0.72 3.74] cases per million) in the 16 to 34 years population. Seventeen reports were included in the system review, showing that the epidemiology of TAK varied greatly across the world. The incidence and prevalence were both relatively higher in Asian countries, with the prevalence ranging 3.3-40 cases per million and annual incidence ranging 0.34-2.4 cases per million. Conclusions The prevalence and incidence of TAK in Shanghai was at moderate to high levels among the previous reports. The disease burden varied globally among racial populations.

Bioresorbable vascular scaffolds are expected to replace the traditional metal stent, avoiding the long-term complications of metal stents. However, it is hard for the traditional scaffold manufacturing process to meet the requirements of individualized treatment for vascular lesions, which requires different morphologies. Here, we used a new method of scaffold manufacturing, three-dimensional printing technology, to prepare bioresorbable vascular scaffolds. The fabricated scaffold was loaded with sirolimus mixed with scaffold preparation material for slow drug release. The engineered, drug- loaded, bioresorbable vascular scaffold (BVS) was analyzed and tested in vivo. The scaffolds produced by three-dimensional printing technology exhibited good mechanical properties and in vitro degradation performance. The results also suggested that these scaffolds could maintain effective radial strength after long-term degradation and sustained release of the drug. As a new scaffold preparation method, it may provide a promising idea for developing bioresorbable vascular scaffold technology.

The mixture of GX (guttiferone E and xanthochymol), an inseparable polycyclic polyprenylated acylphloroglucinol (PPAP), showed moderate cytotoxic activities. The chemical transformation of GX yielded three different types of PPAPs (1, 2, and 3/4). A series of analogs were prepared, and the structures of the 40 newly synthesized compounds were elucidated by 1D and 2D NMR and HR-ESI-MS. The derivatives were screened in vitro for antiproliferative activity against five human cancer cell lines: human leukemic cell lines (HEL and K562), cervical cancer cell line (Hela), human breast adenocarcinoma cell line (MCF-7), and human non-small cell lung cancer cell line (A549), using the MTT assay, and most of the derivatives showed good cytotoxic activities. Noticeably, compound 2, a novel tautomer with a hemiketal, exhibited selective cytotoxic activities against HEL (IC50 = 4.79 ± 0.23 μM) and K562 (IC50 = 7.69 ± 0.34 μM) leukemia cells. The mechanism studies indicated that compound 2 induced apoptosis and arrested the cell cycle at the G0/G1 phase in the HEL cell line. Furthermore, compound 2 activated the intrinsic pathway by reducing the expression of anti-apoptotic protein Bcl-2 and cell cycle-specific cyclin D1 and by enhancing the pro-apoptotic protein Bax. Moreover, the caspase-3 and PPRP1 levels were also upregulated. Our present results suggest that compound 2 is a potential candidate for developing novel anti-leukemia agents in the future.

Based on the concept of the active drug delivery of micro- and nanomotors and the longer cycle time in the blood for drug-loaded tubular particles, it is important to develop novel tubular micromotors that could increase drug loading and achieve more effective treatments in the biomedical field. Here, a novel kind of mesoporous tubular micromotor used to load heparin (Hep) and formed via template-assisted electrochemical deposition is presented. Firstly, the mesoporous tubular micromotors were composed of poly(3,4-ethylenedioxythiophene) (PEDOT), mesoporous silica (MS) and manganese dioxide (MnO2), and were simply fabricated via template-assisted electrochemical growth. Then, the drug Hep was loaded into PEDOT/MS/MnO2via a simple soaking process. Finally, the release process, cytotoxicity, and blood compatibility tests and motion study for these mesoporous tubular micromotors of PEDOT/MS/MnO2-Hep were performed. Results indicated that the micromotors we prepared showed good controlled release of Hep, anticoagulant effects, non-cytotoxicity and autonomous motion ability. The new drug carrier and motion mode will give rise to more potential applications of Hep in the biomedical field.

Six rocaglaol derivatives were isolated from Dysoxylum gotadhora, and those compounds showed good cytotoxic activity with IC50 values ranging from 10 to 350 ng/mL against five different cancer cells. Obviously, further total synthesis of rocaglaol derivatives for medical chemistry study is of great significance. Then, twenty six rocaglaol derivatives including 25 new compounds were designed, synthesized, and evaluated for their cytotoxic activities against three human cancer cell lines: human colon cancer cells (HCT116), colorectal cancer stem cells (P6C), and human red leukocyte leukemia cells (HEL), using MTT assay. Most of derivatives showed good cytotoxic activities, with the lowest IC50 being 3.2 nM for HEL cells, which was 169 times stronger than that of the positive control (doxorubicin). Further mechanism study indicated that 11k could significantly suppress MAPK pathway in HCT116 cells, which may responsible for induction of apoptosis and cell cycle arrest.

Aminopeptidase N (APN/CD13) plays an important role in the growth and metastasis, of tumor, and is a potential biomarker for the post-treatment surveillance of cancer reoccurrence and progression of various malignancies. Thus, we have designed and prepared a convenient and ultrasensitive APN-targeting activity-based ratiometric electrochemical molecular substrate (Ala-AFC) for direct real-time monitoring of APN activity in biosamples. The APN in our experiment was used to hydrolyze the alanine moiety of the Ala-AFC probe and, as a result of this hydrolysis, realize concomitantly a cascade reaction to unmask the electrochemical reporter N-alkylated amino ferrocene (AAF). The Ala-AFC probe exhibited high sensitivity with a wide detection range of 0.05-110 ng mL

Accelerated growth in urban populations has become a powerful force for human development, particularly in developed countries. Metropolitan cities are centers for technical and economic advancement, but air pollution, overflowing of water, and other climate effects still pose significant problems related to nature, climate, and the environment. Cities are vulnerable to increasingly dense, diverse, and interdependent urban systems. A single extreme occurrence can contribute to a systemic break-up of a city's infrastructure, often like dominoes. In this paper, a dynamic integration-assisted population management solution (DI-PMS) has been proposed. DI-PMS recognizes that the latest facilities' optimal usage of knowledge and technologies is needed to increase urbanization. They are one of the critical priorities of the weather community. Such integrated urban weather, environmental, and climate services will help cities address dangers including storms, floods, heatwaves, and air pollution, especially in climate change. The goal is to create urban facilities that satisfy communities' unique needs by high-resolution forecasting and pollution reduction climate services, which allow the construction of durable, robust, and thriving cities that support the Sustainable Development Goals. Several recent international surveys to explore these topics have been undertaken. DI-PMS gives a brief description of urban hydrometeorological, climate and air pollution activities, outlines the new urban integrated weather and environmental services concept, and emphasizes the need for science to be implemented.

Hypsampsone A (1) and hyperhexanone F (2), two novel seco-polycyclic polyprenylated acylphloroglucinols, were isolated from Hypericum sampsonii. Hypsampsone A (1) features the first spirocyclic system fused with 5/6/5/5 tetracyclic skeleton. Hyperhexanone F (2) represents the second novel 1,2-seco-bicyclo[3.3.1]-PPAP skeleton. Their structures were established by extensive spectroscopic analysis, computer-assisted structure elucidation software, and calculated electronic circular dichroism spectra. A plausible biogenetic pathway of 1 was also proposed. Compounds 1 and 2 showed moderate multidrug resistance reversal activity to adriamycin (ADR) resistant cancer cell lines, HepG2/ADR and MCF-7/ADR, with the fold-reversals ranging from 16 to 38 at noncytotoxic concentration of 10 μM.

Due to their unique ability to actively move, micro/nanomotors offer the possibility of breaking through the limitations of traditional passive drug delivery systems for the treatment of many diseases, and have attracted the increasing attention of researchers. However, at present, the realization of many advantages of micro/nanomotors in disease treatment in vivo is still in its infancy, because of the complexity and particularity of diseases in different parts of human body. In this Minireview, we first focus on the biosafety and functionality of micro/nanomotors as a biomedical treatment system. Then, we address the treatment difficulties of various diseases in vivo (such as ophthalmic disease, orthopedic disease, gastrointestinal disease, cardiovascular disease, and cancer), and then review the research progress of biomedical micro/nanomotors in the past 20 years, Finally, we propose the challenges in this field and possible future development directions.

The study investigated the effects of the modified conventional glass ionomer cement (GIC) incorporated with casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on biofilm composition of dental caries. Shear bond strength, durability tests, adhesive remnant index (ARI) and scanning electron microscope were used to measure the physical properties. Microhardness and ions release were determined to evaluate anti-demineralization effects; growth of the biofilm and its composition were assessed using MTT assay and Q-PCR assay. All experimental groups exhibited a significant stimulation of ions release, and reduced attenuation of microhardness. Nearly 39% reduction in the bacterial biofilm was observed with 5% CPP-ACP group. The regulation ability is mainly manifested in the inhibition of S. mutans and promotion of S. gordonii. The modified GICs by exhibiting anti-demineralization effects potentially lead to a reduction in the cariogenicity of plaque and can serve as a putative promising remineralization system with both enhanced antimicrobial and remineralization properties.

Two novel polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperfols A (

Formaldehyde is a reactive carbonyl species (RCS) that is produced naturally in the human body via metabolic and epigenetic biochemical processes, yet in high concentrations is highly toxic to the environment as well as to living organisms. Therefore, we designed two ratiometric electrochemical molecular redox probes, Formaldehyde oxidative latent probe (FOLP) and dihydroxy-formaldehyde oxidative latent probe (HFOLP), for the selective profiling of endogenous formaldehyde. FOLP and HFOLP each underwent the aza-Cope reaction with formaldehyde followed by hydrolysis to eliminate unmask redox reporter N-alkylated aminoferrocene (AAF) to monitor their response current. The FOLP and HFOLP sensors showed broad dynamic ranges of 0.12–1000 μM and 0.09–3 mM for formaldehyde with detection limits of 48.2 nM and 31.6 μM, respectively. Also, since formaldehyde is the byproduct of biochemical reactions for detecting creatinine and creatinine is an important biomarker for chronic kidney disease (CKD), we tested the FOLP probe for its ability to monitor creatinine. It successfully did so, and this ability was used to develop an electrochemical platform for the quantification of creatinine; it showed a dynamic range of 3.25–200 μM and a limit of detection (1.3 μM). In addition, the FOLP-based assay platform delivered a reliable analytical performance for the quantification of formaldehyde in human whole blood and of creatinine in saliva, and also for the real-time monitoring of endogenous formaldehyde secretion in HeLa cells. Moreover, the concentrations determined using our method were found to be consistent with those determined using formaldehyde and creatinine fluorometric assay kits.

Atherosclerosis can lead to thrombosis, blood supply disorders, and even serious consequences such as lumen occlusion or wall rupture and bleeding, so it is urgent to develop an effective comprehensive therapy. Here, a novel kind of drug-coated balloon, where drug-loaded porous nanomotors with autonomous motion ability are used as the coating of the balloon, is reported. The drug-loaded porous nanomotors based on Janus aminated mesoporous silica (JAMS) that was obtained by asymmetric modification of platinum (Pt) nanoparticles are prepared and characterized. The platelet membrane is used to wrap the nanomotors to reduce the leakage of drugs before reaching the plaque. The motion ability of the nanomotor under the irradiation of near-infrared light, the sustained release behavior and effect of the loaded drugs (anti-proliferative drug paclitaxel and the anti-vascular cell adhesion molecule-1 antibody) are investigated in detail. The biomimetic effect and encapsulation effect on drug loading of the platelet membrane, and the elimination of inflammatory macrophages under the photothermal effect produced by Pt are also characterized. The results indicate that the drug-loaded porous nanomotors proposed for drug balloon coating in this work can penetrate into the plaque and enhance the drug retention efficiency, realizing short-term photothermal elimination of inflammatory macrophages and long-term anti-proliferation effect of the drug, providing a possible choice for drug balloon coating with high efficiency in the treatment of atherosclerosis.

Two new abietane diterpenoids, (3S,5R,10S)-3-hydroxy-12-O-demethyl-11-deoxy-19(4→3)-abeo-cryptojaponol, 12,19-dihydroxyabieta-8,11,13-trien-7-one, were isolated from Selaginella moellendorffii Hieron., together with one known abietane diterpenoid and four known tetracyclic triterpenoids. Their structures were characterized by their 1D- and 2D-NMR, ECD and mass spectral studies. All compounds were tested for their inhibitory effects on proliferation of three human cancer cells (human non-small-cell lung carcinoma cell lines A549 and human breast adenocarcinoma cell lines MDA-MB-231 and MCF-7) in vitro. Among them, three compounds displayed modest cytotoxic activities against the above three human cancer cell lines with IC50 values ranging from 16.28 to 40.67 μM.

This research aims to collect speech samples from patients with cleft palate, establish a mandarin-based database of cleft palate speech after sample analysis and classification, and provide a reference for the diagnosis of hypernasal or cleft palate, clinical education, and standard training for professional speech therapists and related research.A total of 768 speech samples were collected from patients and volunteers from the Speech Therapy Center, West China Hospital of Stomatology, between May 2016 and March 2018. These samples were edited and categoried before being saved into the cleft lip and palate biologic information database.A mandarin-based database of cleft palate speech was established from 768 subjects, including 456 children (male 227, female 229), 312 adults (male 178, female 134), 369 normal speech voices, 155 low-level hypernasal samples, 102 moderate-level hypernasal samples, 142 high-level hypernasal samples, and 64 512 words, 24 576 phonemes, and 7 680 numbers.This study first established a mandarin-based database of cleft palate speech, which has enormous value for the education of speech pathology of cleft palate in mandarin and further research.目的 收集腭裂患者语音样本，统一进行归类标注、分级、整理后建立汉语普通话腭裂语音数据库，对于高鼻音乃至腭裂语音的诊断、临床教学、腭裂专业语音师的规范培训以及腭裂语音相关的科研工作建立基础。方法 收集2016年5月—2018年3月四川大学华西口腔医院语音治疗中心的患者与志愿者共768人，按照汉语普通话标准评估材料，收集语音样本，对所有的语音样本进行切分和按照高鼻音等级分类，整理后放入四川大学华西口腔医院唇腭裂生物信息数据库平台。结果 数据库纳入被采集者共768人，其中儿童456人（男227，女229），成人312人（其中男178，女134），正常共鸣369人，轻度高鼻音155人，中度高鼻音102人，重度高鼻音142人。包括64 512个词语、24 576个音素、7 680个数字，完成汉语普通话语音高鼻音数据库的搭建。结论 本研究首次建立了针对汉语普通话腭裂高鼻音数据库，已经为多项语音信号研究提供了源数据，并投入临床教学，未来对于汉语普通话腭裂患者的诊断教学以及相关科研活动有着重要的帮助和指导作用。.

Abundant evidence has illustrated that long non-coding RNA (lncRNA) plays a vital role in the regulation of tumor development and progression. Ectopic expression of a novel lncRNA, termedA total of 159 paired colorectal cancer specimens and adjacent tissues was applied to detect the expression ofWe found that the expression of

Most of the current non-pharmacological treatment strategies for atherosclerosis (AS) suffer from poor penetration into the plaque and only aim at a certain factor in its formation process, resulting in limited therapeutic effect. Herein, a kind of nanomotor with dual-mode propulsion is constructed, which is sensitive to higher reactive oxygen species (ROS) at the AS site and near-infrared (NIR) laser by the covalent binding and self-assembly of β-cyclodextrin (β-CD) and L-arginine (LA) with immobilization of Au nanoparticles. NIR laser irradiation can be used as a driving force and to ablate inflammatory macrophages through the photothermal effect. The nitric oxide (NO) released by the nanomotors can be used as another driving force and a therapeutic agent to promote endothelial repair in the plaque site. LA can eliminate ROS in the inflammatory site, and β-CD can promote the removal of cholesterol from foam cells. In particular, the two driving modes of nanomotors synergistically promote their aggregation and penetration in the plaque. This kind of nanomotor can regulate the microenvironment of AS in multiple ways, including combination therapy for endothelial repair, lipid clearance, and reducing ROS, which is expected to become a potential non-pharmacological strategy in the treatment of AS.

The severe acute respiratory syndrome coronavirus 2 has caused a worldwide pandemic. Control measures differ among countries and have a varying degree of effectiveness, which requires assessment. To evaluate the effectiveness of public health interventions of the coronavirus disease 2019 (COVID-19) in Guangzhou by 3 periods according to interventions: January 7 to 22 (no intervention), January 23 to February 23 (implemented intensive interventions), and February 24 to May 17 (the normalization mode of COVID-19 prevention and control).We collected the information of 745 COVID-19 patients and their close contacts as well as control measures in Guangzhou from January 7 to May 17, 2020. We estimated the epidemiological characteristics, disease spectrum of COVID-19 cases, key time-to-event intervals, and effective reproduction number over the 3 periods. The basic reproduction number of severe acute respiratory syndrome coronavirus 2 was also calculated over period 1.Approximately 45.8%, 49.8%, and 4.4% of cases from close contacts were asymptomatic, symptomatic, and severe, respectively. The median incubation period was 5.3 days (the percentiles of 2.5-97.5, 1.5-18.4 days) and the median serial interval fitted with gamma distribution was 5.1 days (the percentiles of 2.5-97.5, 0.8-15.9 days). The estimated median of onset-to-quarantined time in Period 1 to 3 were 7.5, 3.4, and 2.9 days (the percentiles of 2.5-97.5, 2.1-14.2, 3.9-14.7, and 6.0-20.0 days) respectively and the median of onset-to-confirmation time in period 1 to 3 were 8.9, 4.9 and 2.4 days (the percentiles of 2.5-97.5, 2.6-16.6, 0.9-14.6, and 0.5-11.8 days). In period 1, the reproduction number was 0.9 (95% confidence interval, 0.5-1.4) and fluctuated below 1.0 before January 22 except for January 14. The effective reproduction number gradually decreased in the period 2 with the lowest point of 0.1 on February 20, then increased again since March 27 and reach a spike of 1.8 on April 12. The number decreased to below 1.0 after April 17 and decreased further to0.2 after May 7 in the period 3.Under prospective dynamic observation, close contacts turned into infected cases could provide a spectrum of COVID-19 cases from real-world settings. The lockdown of Wuhan and closed-loop management of people arriving Guangzhou were effective in halting the spread of the COVID-19 cases to Guangzhou. The spread of COVID-19 was successfully controlled in Guangzhou by social distancing, wearing a face mask, handwashing, disinfection in key places, mass testing, extensive contact tracing, and strict quarantine of close contacts.

Leukemia is responsible for a reason of death, globally. Even though there are several treatment regimens available in the clinics against this disease, a perfect chemotherapeutic agent for the same is still under investigation. Natural plant-derived secondary metabolites are used in clinics to treat leukemia for better benefits with reduced side-effects. Likely, several bioactive compounds from Callistemon sp. were reported for their bioactive benefits. Furthermore, acylphloroglucinol derivatives from Callistemon salignus, showed both antimicrobial and cytotoxic activities in various adherent human cancer cell lines. Thus, in the present study, a natural acylphloroglucinol (2,6-dihydroxy-4-methoxyisobutyrophenone, L72) was tested for its antiproliferative efficacy in HEL cells. The MTT and the cell cycle analysis study revealed that L72 treatment can offer antiproliferative effects, both time and dose-dependent manner, causing G2/M cell cycle arrest. The western blot analysis revealed that L72 treatment triggered intrinsic apoptotic machinery and activated p21. Likewise, L72 could downregulate the gene expressions of XIAP, FLT3, IDH2, and SOD2, which was demonstrated by qPCR analysis, thus promoting its antiproliferative action. The L72 could impede STAT3 expression, which was evidenced by insilico autodock analysis and western blot analysis using STAT3 inhibitor, Pimozide. The treatment of transgenic (Flk-1+/egfr+) zebrafish embryos resulted in the STAT3 gene inhibition, proving its anti-angiogenic effect, as well. Thus, the study revealed that L72 could act as an antiproliferative agent, by triggering caspase-dependent intrinsic apoptosis, reducing cell proliferation by attenuating STAT3, and activating an anti-angiogenic pathway via Flk-1inhibition.

Superoxide anion (O2•-), one of the most active reactive oxygen species (ROS) in micro-environment of the human body, is involved in some diseases if there is excess O2•- associated with oxidative stress. Accurate detection of its concentration has important medical diagnostic significance. In this work, a new electrochemical sensor was designed and fabricated for sensitive detection based on Mn-superoxide dismutase (MnSOD) that decorated onto the surface of magnetic polymeric nanotubes by surface self-assembly processes. The composite nanotubes were characterized by transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FTIR), Zeta potential analyzer, energy dispersive spectroscopy (EDS) and vibrating sample magnetometer(VSM), and the biosensor exhibited excellent analytical performance, for example, the interference could be eliminated with high selectivity, the linear range from 0.15 to 3.0μM with a detection limit of 0.0136μM (S/N=3)，Cyclic voltammogram (CV) curves of the biosensor for 30 overlapping cycles showed the biosensor had a good cycle stability. Results indicated that the magnetic polymeric nanotubes that decorated by Mn3(PO4)2 nanoparticles could effectively catalyze the dismutation of O2•- that attributed to its high surface areas and a large number of active sites of self-assembled Mn3(PO4)2 nanoparticles. This method combining nanotechnology and self-assembly technique provided a new appropriate platform to design and fabricate electrochemical sensor with high performance.

Accurate values of tumor markers in blood play an especially important role in the diagnosis of illness. Here, based on the combination of three techniques include anticoagulant technology, nanotechnology and biosensing technology, a sensitive label-free immunosensor with anti-biofouling electrode for detection α-Fetoprotein (AFP) in whole blood was developed by anticoagulating magnetic nanoparticles. The obtained products of Fe3O4-ɛ-PL-Hep nanoparticles were characterized by fourier transform infrared (FT-IR) spectra, transmission electron microscopy (TEM), ζ-potential and vibrating sample magnetometry (VSM). Moreover, the blood compatibility of anticoagulating magnetic nanoparticles was characterized by in vitro coagulation tests, hemolysis assay and whole blood adhesion tests. Combining the anticoagulant property of heparin (Hep) and the good magnetism of Fe3O4, the Fe3O4-ɛ-PL-Hep nanoparticles could improve not only the anti-biofouling property of the electrode surface when they contact with whole blood, but also the stability and reproducibility of the proposed immunosensor. Thus, the prepared anticoagulating magnetic nanoparticles modified immunosensor for the detection of AFP showed excellent electrochemical properties with a wide concentration range from 0.1 to 100ng/mL and a low detection limit of 0.072ng/mL. Furthermore, five blood samples were assayed using the developed immunosensor. The results showed satisfactory accuracy with low relative errors. It indicated that our developed immunoassay was competitive and could be potentially used for the detection of whole blood samples directly.

A novel label-free immunosensor based on hyperbranched polyester nanoparticles with nitrite groups (HBPE-NO2), which were synthesized through a simple one-step chemical reaction, was first developed for specific detection of α-fetoprotein (AFP), the tumor marker for liver cancer. The obtained HBPE-NO2 nanoparticles (NPs) were characterized by the proton nuclear magnetic resonance spectroscopy (1H NMR), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). And the fabricated process of immunosensor was investigated by attenuated total reflection Fourier-transform infrared spectra (ATR-FTIR), static water contact angles, scanning electron microscope (SEM), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The electrochemical performances of the AFP immunosensor were studied. Results indicated the prepared HBPE-NO2-modified immunosensor showed excellent electrochemical properties and satisfactory accuracy for the detection of AFP of the real clinical samples that attributed to the properties of the HBPE-NO2 NPs, which had nanosized structure to increase the specific surface area and unique chemical reactivity for loading capacity of protein molecules. Construction of biosensors using the structure and properties of hyperbranched molecules will offer ideal electrode substrates, which provided more possibilities for the design of biosensor.

// Yu-Chieh Lee 1, 9 , Chia-Yu Su 2 , Yuan-Feng Lin 3 , Chun-Mao Lin 4 , Chih-Yeu Fang 7 , Yen-Kuang Lin 8 , Michael Hsiao 2, 10 , Chi-Long Chen 5, 6 1 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan 2 Genomics Research Center, Academia Sinica, Taipei, Taiwan 3 Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan 4 Department of Biochemistry, School of Medicine, Taipei Medical University, Taipei, Taiwan 5 Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan 6 Department of Pathology, Taipei Medical University Hospital, Taipei, Taiwan 7 Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan 8 Biostatistics Center, Taipei Medical University, Taipei, Taiwan 9 Division of Gastroenterology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan 10 Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Correspondence to: Chi-Long Chen, email: chencl@tmu.edu.tw Michael Hsiao, email: mhsiao@gate.sinica.edu.tw Keywords: colorectal carcinoma, lysosomal acid phosphatase 2, 5-FU, chemotherapy Received: July 05, 2016 Accepted: December 27, 2016 Published: January 06, 2017 ABSTRACT Colorectal cancer (CRC) is one of the leading cancers worldwide. Surgery is the main therapeutic modality for stage II CRC. However, the implementation of adjuvant chemotherapy remains controversial and is not universally applied so far. In this study, we found that the protein expression of lysosomal acid phosphatase 2 (ACP2) was increased in CRC and that stage II CRC patients with high ACP2 expression showed a poorer outcome than those with low ACP2 expression ( p = 0.004). To investigate this discrepancy, we analyzed the relation between ACP2 expression and several clinical cofactors. Among patients who received chemotherapy, those with an high expression of ACP2 showed better survival in both stage II and III CRC than those with low ACP2 expression. In stage II CRC patients, univariate analysis showed ACP2 expression and T stage to be cofactors significantly associated with overall survival (ACP2: p = 0.006; T stage: p = 0.034). Multivariate Cox proportion hazard model analysis also revealed ACP2 to be an independent prognostic factor for overall survival (ACP2: p = 0.006; T stage: p = 0.041). Furthermore, ACP2-knockdown CRC cells showed an increase in chemoresistance to 5-FU treatment and increased proliferation marker in the ACP2 knockdown clone. Taken together, our results suggested that ACP2 is an unfavorable prognostic factor for stage II CRC and may serve as a potential chemotherapy-sensitive marker to help identify a subset of stage II and III CRC patients for whom chemotherapy would improve survival. Highlights 1. To the best of our knowledge, the study is the first report to show ACP2 overexpression in human colorectal cancer (CRC) and its association with poor outcome in stage II CRC. 2. Patients with stage II and III CRCs with high expression of ACP2 were more sensitive to chemotherapy than those with a low expression. 3. ACP2 expression may serve as a marker for CRC patients receiving chemotherapy and help identify the subset of CRC patients who would benefit from chemotherapy.

Background MAPK/ERK kinases transmit signals from many growth factors/kinase receptors during normal cell growth/differentiation, and their dysregulation is a hallmark of diverse types of cancers. A plethora of drugs were developed to block this kinase pathway for clinical application. With the exception of a recently identified agent, EQW, most of these inhibitors target upstream factors but not ERK1/2; no activator of ERK1/2 is currently available. Method A library of compounds isolated from medicinal plants of China was screened for anti-cancer activities. Three limonoid compounds, termed A1541–43, originally isolated from the plant Melia azedarach, exhibiting strong anti-leukemic activity. The anti-neoplastic activity and the biological target of these compounds were explored using various methods, including western blotting, flow cytometry, molecular docking and animal model for leukemia. Results Compounds A1541–43, exhibiting potent anti-leukemic activity, was shown to induce ERK1/2 phosphorylation. In contrast, the natural product Cedrelone, which shares structural similarities with A1541–43, functions as a potent inhibitor of ERK1/2. We provided evidence that A1541–43 and Cedrelone specifically target ERK1/2, but not the upstream MAPK/ERK pathway. Computational docking analysis predicts that compounds A1541–43 bind a region in ERK1/2 that is distinct from that to which Cedrelone and EQW bind. Interestingly, both A1541–43, which act as ERK1/2 agonists, and Cedrelone, which inhibit these kinases, exerted strong anti-proliferative activity against multiple leukemic cell lines, and induced robust apoptosis as well as erythroid and megakaryocytic differentiation in erythroleukemic cell lines. These compounds also suppressed tumor progression in a mouse model of erythroleukemia. Conclusions This study identifies for the first time activators of ERK1/2 with therapeutic potential for the treatment of cancers driven by dysregulation of the MAPK/ERK pathway and possibly for other disorders. Electronic supplementary material The online version of this article (10.1186/s12885-019-5914-8) contains supplementary material, which is available to authorized users.

A series of novel parthenolide–thiazolidinedione hybrids have been synthesized via a click chemistry-mediated coupling between parthenolide and thiazolidinedione, and evaluated for their cytotoxic activities. The results indicated that all the hybrids showed moderate cytotoxic effects on human cancer cell lines, including human erythroleukemia cell line (HEL), prostate (PC3), and breast (MDA-MB-231) by MTT assay. In particular, compound VI-6 exhibited the best cytotoxic activities against the MDA-MB-231 cells with IC50 value of 2.07 µM, which was about eight times more active than that of the original compound (PTL). These interesting results might be used to develop novel lead scaffolds for potential anticancer agents.

Nine undescribed compounds, including five xanthone derivatives, two flavonoids, one 2-pyrone derivative, and one undescribed naturally occurring compound, along with 30 known phenolic compounds, were isolated from Hypericum japonicum. In addition, hyperjaponols A and B were identified as racemates. The structures and absolute configurations of the undescribed compounds were determined by comprehensive MS, NMR spectroscopy, and electronic circular dichroism (ECD) calculations. The cytotoxic effects of the isolated compounds on two human tumour cell lines (HEL and MDA-MB-231) were evaluated by the MTT assay. Eighteen compounds showed good inhibitory activities against the HEL cell line, with IC50 values of 3.53–18.7 μM, while nine compounds exhibited moderate cytotoxicity against the MDA-MB-231 cancer cell line, with IC50 values ranging from 4.92 to 10.75 μM. Their preliminary structure-activity relationship of the isolated compounds was also discussed.

Chronic kidney disease (CKD) is inflammation-related. Patients with chronic renal failure who undergo hemodialysis (HD) have some acute adverse effects caused by dialysis-induced oxidative stress, protein adsorption, platelet adhesion, and activation of coagulation and inflammation. Here, resonantly illuminated gold nanoparticles-modified artificial kidney (AuNPs@AK) for achieving high efficiency accompanying therapeutic strategy for CKD during HD is proposed. The efficiency in removing uremic toxins increased obviously, especially in the presence of protein (closer to the real blood). The excited AuNPs@AK expressed negatively charged surface reduced some acute adverse effects caused by dialysis-induced protein adsorption, platelet adhesion, and activation of coagulation, thus avoiding thrombosis during HD. Unlike to traditional HD which provides only one function of removing uremic toxins, the solution collected from the outlet of the sample channel of excited AuNPs@AK showed an efficient free radical scavenger that could decrease dialysis-induced oxidative stress. In the CKD mouse model, this antioxidative solution from excited AuNPs@AK further decreased fibronectin expression and attenuated renal fibrosis, suggesting a reduced inflammatory response. These successful in vitro and in vivo approaches suggest that resonantly illuminated AuNPs@AK in HD take multiadvantages in shortening treatment time and reducing risk of adverse effects, which promise trailblazing therapeutic strategies for CKD.