The regulation of microRNAs on chemoresistance in triple-negative breast cancer: a recent update.

Triple-negative breast cancer (TNBC) has negative expressions of ER, PR and HER2. Due to the insensitivity to both endocrine therapy and HER2-targeted therapy, the main treatment method for TNBC is cytotoxic chemotherapy. However, the curative effect of chemotherapy is limited because of the existence of acquired or intrinsic multidrug resistance. MicroRNAs (miRNAs) are frequently dysregulated in malignant tumors and involved in tumor occurrence and progression. Interestingly, growing studies show that miRNAs are involved in chemoresistance in TNBC. Thus, targeting dysregulated miRNAs could be a plausible way for better treatment of TNBC. Here, we present the updated knowledge of miRNAs associated with chemoresistance in TNBC, which may be helpful for the early diagnosis, prognosis and treatment of this life-threatening disease.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer, which is characterized by high rates of invasion, recurrence and distant metastasis. At present, chemotherapy is still the main treatment option for TNBC. However, after some time, the sensitivity of tumor cells to chemotherapeutic drugs gradually decreases, which makes tumor cells develop chemoresistance. MicroRNAs (miRNAs) are a class of small RNA molecules with length of 19­25 nucleotides that do not encode proteins. The expression level of miRNAs in cancer is usually abnormal. More and more studies have shown that miRNAs are involved in cancer development and associated with drug resistance. Therefore, this review summarizes the miRNAs associated with chemoresistance in TNBC.

Protective Effect of Silibinin on Lipopolysaccharide-Induced Endotoxemia by Inhibiting Caspase-11-Dependent Cell Pyroptosis.

OBJECTIVE: To explore the protective effect and the underlying mechanism of silibinin (SIB), one of the active compounds from Silybum marianum (L.) Gaertn in endotoxemia. METHODS: Mouse peritoneal macrophage were isolated via intraperitoneally injection of BALB/c mice with thioglycolate medium. Cell viability was assessed using the cell counting kit-8, while cytotoxicity was determined through lactate dehydrogenase cytotoxicity assay. The protein expressions of interleukin (IL)-1 α, IL-1 ß, and IL-18 were determined by enzyme-linked immunosorbent assay. Intracellular lipopolysaccharide (LPS) levels were measured by employing both the limulus amoebocyte lysate assay and flow cytometry. Additionally, proximity ligation assay was employed for the LPS and caspase-11 interaction. Mice were divided into 4 groups: the control, LPS, high-dose-SIB (100 mg/kg), and low-dose-SIB (100 mg/kg) groups (n=8). Zebrafish were divided into 4 groups: the control, LPS, high-dose-SIB (200 εmol/L), and low-dose-SIB (100 εmol/L) groups (n=30 for survival experiment and n=10 for gene expression analysis). The expression of caspase-11, gasdermin D (GSDMD), and N-GSDMD was determined by Western blot and the expressions of caspy2, gsdmeb, and IL-1 ß were detected using quantitative real-time PCR. Histopathological observation was performed through hematoxylineosin staining, and protein levels in bronchoalveolar lavage fluid were quantified using the bicinchoninicacid protein assay. RESULTS: SIB noticeably decreased caspase-11 and GSDMD-mediated pyroptosis and suppressed the secretion of IL-1 α, IL-1 ß, and IL-18 induced by LPS (P<0.05). Moreover, SIB inhibited the translocation of LPS into the cytoplasm and the binding of caspase-11 and intracellular LPS (P<0.05). SIB also attenuated the expression of caspase-11 and N-terminal fragments of GSDMD, inhibited the relative cytokines, prolonged the survival time, and up-regulated the survival rate in the endotoxemia models (P<0.05). CONCLUSIONS: SIB can inhibit pyroptosis in the LPS-mediated endotoxemia model, at least in part, by inhibiting the caspase-11-mediated cleavage of GSDMD. Additionally, SIB inhibits the interaction of LPS and caspase-11 and inhibits the LPS-mediated up-regulation of caspase-11 expression, which relieves caspase-11-dependent cell pyroptosis and consequently attenuates LPS-mediated lethality.

Nitrate Quantification in Fresh Vegetables in Shanghai: Its Dietary Risks and Preventive Measures.

To investigate nitrate and nitrite content in fresh vegetables, 264 samples were randomly collected in the farmers' markets in Shanghai, Southeast China. The results indicate that 25.0% of the fresh vegetables were critically or more contaminated by nitrate [>1440 mg/kg FW (Fresh weight)]. Generally, leafy vegetables were more highly enriched in nitrate than root-tuber and fruit vegetables. About 22.6% of the leafy vegetables had a nitrate content exceeding the limit for edible permission (>3000 mg/kg FW). Nitrite content in the fresh vegetables was all within the safe level (<1 mg/kg FW). It was estimated that the daily nitrate intake through eating vegetables in Shanghai exceeded the WHO/FAO allowable limit. The field experiment indicated that the hyper-accumulation of nitrate and nitrite in the vegetables was mainly attributed to the excessive application of chemical fertilizers. The maxima of nitrate and nitrite in the vegetables were attained one week after applying chemical fertilizer, and thus they cannot be picked for dietary use. Applying organic manure can effectively lower the risk of nitrate and nitrite contamination in vegetables. The old leaves and leaf petioles were more easily enriched in nitrate due to their weaker metabolic activity. Vegetables with high nitrate content had a high risk of nitrite toxicity during storage due to the biological conversion of nitrate into nitrite, which is easily triggered by suitable temperature and mechanical damage processing. Therefore, fresh vegetables should be stored by rapid cooling and in undamaged forms to prevent nitrite accumulation.

J-shaped association between the visceral adiposity index and all-cause mortality in patients with chronic kidney disease.

OBJECTIVE: Visceral obesity, assessed using the visceral adiposity index (VAI), is related to mortality, but studies of populations with chronic kidney disease (CKD) are scarce. The aim of this study was to evaluate the relationship between VAI and all-cause mortality among individuals with CKD. METHODS: We retrospectively explored the relationship between VAI and risk for all-cause death by analyzing the data of 4145 patients with CKD who participated in the National Health and Nutrition Examination Survey (NHANES) 2001-2006. Patients were followed until December 31, 2015. RESULTS: After an average follow-up of 134.14 mo, 1034 (24.95%) deaths were recorded. Comparison of VAI quartiles with the reference showed an unstable association of VAI with all-cause mortality after adjusting for a wide range of potential confounders in Cox regression analysis. The correlation between VAI and mortality was J-shaped after applying the penalized spline method. Before the inflection point (VAI = 68.23), higher VAI had a protective effect against mortality (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.28-0.77). However, the risk for all-cause mortality gradually increased with the VAI (HR, 1.13; 95% CI, 1.05-1.21). CONCLUSION: Visceral obesity may influence the rate of all-cause mortality in a nonlinear manner in populations with CKD. Risk for death was higher with visceral fat deficiency than with excessive visceral fat deposition.

Higher dietary inflammatory index is associated with increased all-cause mortality in adults with chronic kidney disease.

Background: Diet property grounded on inflammatory potential, evaluated by the dietary inflammatory index (DII), has been proven to be connected with mortality, while studies of adults with chronic kidney disease (CKD) are scarce. Objective: The purpose of this research was to evaluate the interrelationships between DII and all-cause mortality among adults with CKD. Methods: In the National Health and Nutrition Examination Survey (NHANES) 2001-2006, we identified and evaluated data of 4,554 adults with CKD. DII scores were calculated from 24 h of dietary consumption at baseline. Vital status was followed through 31 December 2015. The association of all-cause mortality with DII score was assessed using the Kaplan-Meier curve and the Cox regression analysis. Results: After an average follow-up of 132.103 months, a total of 1,246 (27.36%) deaths were recorded. The death rates in the DII tertile categories were 24.04, 26.81, and 31.23%, respectively. The Kaplan-Meier curve showed increased death risks for the high DII tertile as compared with the low DII tertile. After we adjusted for a broad range of possible confounders, the estimation between extreme tertiles of DII scores presented a positive and significant association with all-cause mortality [hazard ratio (HR): 1.21, 95% CI: 1.05-1.39]. Conclusion: Our results confirm the hypothesis that proinflammatory diets contribute to the increased all-cause mortality in adults with CKD.

Characterization of the complete plastid genome of Scutellaria microviolacea (Lamiaceae), a species endemic to Yunnan Province of China.

The complete plastid genome of Scutellaria microviolacea C. Y. Wu was firstly reported. The full length of the plastid genome was 152,092 bp and comprised of a large single-copy (LSC) region of 84,090 bp, a small single-copy (SSC) region of 17,534 bp, and two inverted repeat regions (IRs) of 25,234 bp. A total of 131 genes were encoded, including 87 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. The overall GC content of the S. microviolacea plastid genome was 38.3%. Further phylogenetic analysis based on 18 accessions inferred that the genus Scutellaria can be divided into two clades, and S. microviolacea is evolutionarily close to Scutellaria tsinyunensis. Our study provided essential genetic resources for further studies on the evolution and genetic diversity of the genus Scutellaria and its related taxa.

NPM2 in malignant peritoneal mesothelioma: from basic tumor biology to clinical medicine.

BACKGROUND: This review systematically summarizes gene biology features and protein structure of nucleoplasmin2 (NPM2) and the relationship between NPM2 and malignant peritoneal mesothelioma (MPM), in order to explore the molecular pathological mechanism of MPM and explore new therapeutic targets. METHODS: NCBI PubMed database was used for the literature search. NCBI Gene and Protein databases, Ensembl Genome Browser, UniProt, and RCSB PDB database were used for gene and protein review. Three online tools (Consurf, DoGSiteScorer, and ZdockServer), the GEPIA database, and the Cancer Genome Atlas were used to analyze bioinformatics characteristics for NPM2 protein. RESULTS: The main structural domains of NPM2 protein include the N-terminal core region, acidic region, and motif and disordered region. The N-terminal core region, involved in histone binding, is the most conserved domain in the nucleoplasmin (NPM) family. NPM2 with a large acidic tract in its C-terminal tail (NPM2-A2) is able to bind histones and form large complexes. Bioinformatics results indicated that NPM2 expression was correlated with the pathology of multiple tumors. Among mesothelioma patients, 5-year survival of patients with low-NPM2-expression was significantly higher than that of the high-NPM2-expression patients. NPM2 can facilitate the formation of histone deacetylation. NPM2 may promote histone deacetylation and inhibit the related-gene transcription, thus leading to abnormal proliferation, invasion, and metastasis of MPM. CONCLUSION: NPM2 may play a key role in the development and progression of MPM.

Emodin Protects Against Lipopolysaccharide-Induced Acute Lung Injury via the JNK/Nur77/c-Jun Signaling Pathway.

Background: Acute lung injury (ALI) is a serious inflammatory disease with clinical manifestations of hypoxemia and respiratory failure. Presently, there is no effective treatment of ALI. Although emodin from Rheum palmatum L. exerts anti-ALI properties, the underlying mechanisms have not been fully explored. Purpose: This study aimed to investigate the therapeutic effect and mechanism of emodin on LPS-induced ALI in mice. Methods: RAW264.7 cells and zebrafish larvae were stimulated by LPS to establish inflammatory models. The anti-inflammatory effect of emodin was assessed by ELISA, flow cytometric analysis, and survival analysis. In vitro mechanisms were explored by using Western blotting, luciferase assay, electrophoretic mobility shift assay (EMSA), and small interfering RNA (siRNA) approach. The acute lung injury model in mice was established by the intratracheal administration of LPS, and the underlying mechanisms were assessed by detecting changes in histopathological and inflammatory markers and Western blotting in lung tissues. Results: Emodin inhibited the inflammatory factor production and oxidative stress in RAW264.7 cells, and prolonged the survival of zebrafish larvae after LPS stimulation. Emodin suppressed the expression levels of phosphorylated JNK at Thr183/tyr182 and phosphorylated Nur77 at Ser351 and c-Jun, and increased the expression level of Nur77 in LPS-stimulated RAW264.7 cells, while these regulatory effects of emodin on Nur77/c-Jun were counteracted by JNK activators. The overexpression of JNK dampened the emodin-mediated increase in Nur77 luciferase activity and Nur77 expression. Moreover, the inhibitory effect of emodin on c-Jun can be attenuated by Nur77 siRNA. Furthermore, emodin alleviated LPS-induced ALI in mice through the regulation of the JNK/Nur77/c-Jun pathway. Conclusions: Emodin protects against LPS-induced ALI through regulation on JNK/Nur77/c-Jun signaling. Our results indicate the potential of emodin in the treatment of ALI.

Natural hybridization among three Rhododendron species (Ericaceae) revealed by morphological and genomic evidence.

BACKGROUND: Natural hybridization can influence the adaptive response to selection and accelerate species diversification. Understanding the composition and structure of hybrid zones may elucidate patterns of hybridization processes that are important to the formation and maintenance of species, especially for taxa that have experienced rapidly adaptive radiation. Here, we used morphological traits, ddRAD-seq and plastid DNA sequence data to investigate the structure of a Rhododendron hybrid zone and uncover the hybridization patterns among three sympatric and closely related species. RESULTS: Our results show that the hybrid zone is complex, where bi-directional hybridization takes place among the three sympatric parental species: R. spinuliferum, R. scabrifolium, and R. spiciferum. Hybrids between R. spinuliferum and R. spiciferum (R. ×duclouxii) comprise multiple hybrid classes and a high proportion of F1 generation hybrids, while a novel hybrid taxon between R. spinuliferum and R. scabrifolium dominated the F2 generation, but no backcross individuals were detected. The hybrid zone showed basically coincident patterns of population structure between genomic and morphological data. CONCLUSIONS: Natural hybridization exists among the three Rhododendron species in the hybrid zone, although patterns of hybrid formation vary between hybrid taxa, which may result in different evolutionary outcomes. This study represents a unique opportunity to dissect the ecological and evolutionary mechanisms associated with adaptive radiation of Rhododendron species in a biodiversity hotspot.

Serum Folate and All-Cause Mortality is of Non-Linear Relationship Among Population with Chronic Kidney Disease: A Retrospective Cohort Study.

AIM: A transition toward high serum folate concentrations has been noticed following the mandatory folate fortification. To explore this further, we studied the relationship between folate and health outcomes in population with chronic kidney disease (CKD). METHODS: We retrospectively explored the relationships between serum folate and risk of all-cause death in this population. We analyzed data of 2142 subjects with CKD who participated in the National Health and Nutrition Examination Survey (NHANES) 1999-2006. Vital status was followed through December 31, 2006. RESULTS: Cox regression was used to estimate hazard ratios (HRs) of mortality for individuals with serum folate in rest quintiles compared with individuals with the fourth quintile. After an average follow-up of 57.4 months with 157 deaths recorded, a reversed J-shaped association was revealed after conducting multivariable adjustment. The mortality rate in population with lower and higher folate levels were 8.29% and 12.67%, respectively, and the corresponding adjusted HRs were 2.41 (95% confidence interval, CI=1.32-4.40) and 2.10 (1.20-3.70). Kaplan-Meier curve showed survival benefits for the fourth quintile of serum folate as compared to the first and fifth quintile. CONCLUSION: Serum folate concentrations may influence all-cause mortality in a non-linear pattern in the CKD population. It is reasonable to recommend periodic surveillance in the CKD population to maintain the serum folate concentration in an appropriate level.

The complete plastid genome of Aletris megalantha (Nartheciaceae), an endemic species from Yunnan Province of China.

Aletris megalantha F. T. Wang & Tang is an herbal plant species endemic to Yunnan Province of China. Its complete plastid genome sequence was 154,704 bp in length, with a large single-copy (LSC) region of 83,265 bp, a small single-copy (SSC) region of 18,127 bp, and a pair of inverted repeat regions (IRs) of 26,656 bp. The whole plastid genome encoded 132 genes, including 85 protein-coding genes, 38 tRNA genes, and eight rRNA genes. The overall GC content of A. megalantha plastid genome was 37.4%. Maximum likelihood phylogenetic analysis based on 14 taxa indicated that A. megalantha is evolutionarily close to A. spicata.

Sauchinone inhibits hypoxia-induced epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma cells through the Wnt/ß-catenin pathway.

The hypoxic microenvironment is commonly found in various solid tumors including pancreatic ductal adenocarcinoma (PDAC). Saururus chinensis is a medicinal Chinese herb widely used because of documented anti-inflammatory and anti-angiogenic properties. Sauchinone is special active lignin extracted from S. chinensis and its biological functions have been extensively explored. Recent studies have found that sauchinone could affect tumor initiation, metastasis and progression of some cancers. However, the specific role of sauchinone in PDAC remains to be elucidated. The main aim of this study was to elucidate the involvement of sauchinone in the progression of PDAC under the hypoxic condition. The human PDAC cell lines PANC-1 and BxPC-3 were exposed to hypoxia and various concentrations of sauchinone. The CCK-8 assay was performed to detect cytotoxic effects of sauchinone on PDAC cells. The levels of vascular endothelial growth factor, hypoxia-inducible factor-1α, E-cadherin, N-cadherin, Wnt3a and ß-catenin were examined by the western blot analysis. Wound healing and transwell assays were used to assess cell migration and invasion. The results showed that the migratory and invasive abilities of PDAC cells were enhanced after exposure to hypoxia and the expression of epithelial-mesenchymal transition markers was also significantly regulated by hypoxia. All these effects induced under the hypoxic condition were terminated by sauchinone treatment. In addition, sauchinone suppressed hypoxia-induced activation of the Wnt/ß-catenin signaling pathway. Our study provided important insight into understanding the mechanisms of the anti-cancer effect of sauchinone. Taken together, we suggested that sauchinone may be considered a new therapeutic agent for PDAC treatment.

ABCB1 (C1236T) Polymorphism Affects P-Glycoprotein-Mediated Transport of Methotrexate, Doxorubicin, Actinomycin D, and Etoposide.

P-glycoprotein (P-gp), encoded by the ABCB1 (ATP-binding cassette transporter superfamily B member 1) gene, is a transport protein involved in the efflux and distribution of the osteosarcoma drugs methotrexate, doxorubicin, actinomycin D, and etoposide. In vivo studies indicate a close relationship between the ABCB1 (C1236T) single-nucleotide polymorphism (SNP) and the efficacy of these drugs. The purpose of this research was to elucidate the effect of ABCB1 (C1236T) polymorphism on P-gp-mediated efflux of osteosarcoma drugs. Two stable recombinant Caco-2 cell lines were generated by transfection with either the wild-type ABCB11236C allele or the ABCB11236T variant allele. The two cell lines were compared in terms of drug resistance, intracellular accumulation, and efflux of methotrexate, doxorubicin, actinomycin D, and etoposide. Accumulation of methotrexate, doxorubicin, actinomycin D, and etoposide was significantly lower in cells overexpressing wild-type P-gp than in untransfected control cells, indicating that these drugs are substrates of P-gp. Actinomycin D accumulated to similar extents in cells overexpressing wild-type or variant P-gp. Methotrexate and etoposide were transported to a greater extent by variant P-gp than wild-type protein. Conversely, doxorubicin was transported to a greater extent by wild-type P-gp. The ABCB1 (C1236T) polymorphism affects P-gp-mediated transport of osteosarcoma drugs in a drug-specific way. These studies support the importance of the ABCB1 (C1236T) SNP for P-gp activity and its potential to explain the alterations in drug response.

Incomplete reproductive isolation between Rhododendron taxa enables hybrid formation and persistence.

The evolutionary consequences of hybridization ultimately depend on the magnitude of reproductive isolation between hybrids and their parents. We evaluated the relative contributions of pre- and post-zygotic barriers to reproduction for hybrid formation, hybrid persistence and potential for reproductive isolation of hybrids formed between two Rhododendron species, R. spiciferum and R. spinuliferum. Our study established that incomplete reproductive isolation promotes hybrid formation and persistence and delays hybrid speciation. All pre-zygotic barriers to reproduction leading to hybrid formation are incomplete: parental species have overlapping flowering; they share the same pollinators; reciprocal assessments of pollen tube germination and growth do not differ among parents. The absence of post-zygotic barriers between parental taxa indicates that the persistence of hybrids is likely. Reproductive isolation was incomplete between hybrids and parents in all cases studied, although asymmetric differences in reproductive fitness were prevalent and possibly explain the genetic structure of natural hybrid swarms where hybridization is known to be bidirectional but asymmetric. Introgression, rather than speciation, is a probable evolutionary outcome of hybridization between the two Rhododendron taxa. Our study provides insights into understanding the evolutionary implications of natural hybridization in woody plants.

Arteriovenous Graft for Hemodialysis: Effect of Cryotherapy on Postoperative Pain and Edema.

BACKGROUND: Arteriovenous grafting offers an alternative for patients whose vessels are unsuitable for arteriovenous fistula. However, as a result of subcutaneous tunnel dissection, postoperative pain and edema of the operated limb present early after surgery. As a traditional therapeutic approach, cryotherapy has the ability to suppress postoperative pain and edema. AIMS: The purpose of the study was to investigate the feasibility of cryotherapy after arteriovenous graft surgery to decrease perioperative medication usage. DESIGN: This study was a randomized controlled trial. SETTING: A large integrated health care facility in South China. PARTICIPANTS/SUBJECTS: A total of 85 hemodialysis patients who received arteriovenous graft surgery from March 2011 to February 2017 were enrolled. METHODS: The participants were divided into an intervention group and a control group according to the postoperative management. Ice packs were applied covering the operative forearm for 120 minutes after wound closure in the intervention group. General information, pain score, analgesic consumption, wound inflammation, forearm edema, and participant satisfaction were compared between the two groups. RESULTS: Cryotherapy-treated patients required less analgesia (26.19% vs. 48.84%, p < .05), reported lower pain score from 30 minutes to 48 hours postoperative (p < .05), less wound inflammation (11.90% vs. 25.58%, p < .05), and higher participant satisfaction (8.92 ± 0.57 vs. 6.52 ± 0.63, p < .05), whereas the incidence of forearm edema was equivalent (p > .05). No adverse events were reported in either group. CONCLUSIONS: Cryotherapy is a preferable intervention for patients after arteriovenous graft implantation as a result of its favorable cost, convenience, and fewer side effects.

Cryotherapy Relieves Pain and Edema After Inguinal Hernioplasty in Males With End-Stage Renal Disease: A Prospective Randomized Study.

CONTEXT: Tension-free hernioplasty under local anesthetic infiltration is a reasonable choice for end-stage renal disease patients with hernia. OBJECTIVES: The purpose of the study was to investigate the feasibility of cryotherapy after hernioplasty surgery to relieve pain and scrotal edema. METHODS: This was a prospective, randomized, and controlled trial held in a large integrated health care facility in South China. One hundred sixty-nine male patients on hemodialysis and scheduled for hernioplasty were enrolled between March 2013 and February 2017. The participants were divided into an intervention group and a control group. In the intervention group, ice packs were applied after surgery. Demographic information, vital signs, pain score, opioid consumption, wound inflammation, scrotal edema, and patient satisfaction were compared between the two groups. The primary outcome was pain score. RESULTS: Cryotherapy-treated patients required less opioid consumption (5.95 vs. 15.29 mg; P < 0.05), reported lower pain scores from 30 minutes to 48 hours after operation (P < 0.05), less wound inflammation (11.90 vs. 32.94%; P < 0.05), lower incidence of scrotal edema in the first and second days (P < 0.05), and higher patient satisfaction (8.95 vs. 6.50 cm; P < 0.05), with stable vital signs throughout the monitoring period (P > 0.05). CONCLUSION: Owing to its favorable cost, convenience, and low frequency of adverse effects, cryotherapy is useful for end-stage renal disease populations after hernioplasty to relieve pain and scrotal edema.

Green synthesis of new pyrrolidine-fused spirooxindoles via three-component domino reaction in EtOH/H2O.

An efficient, green and sustainable approach for the synthesis of novel polycyclic pyrrolidine-fused spirooxindole compounds was developed. The synthesis included a one-pot, three-component, domino reaction of (E)-3-(2-nitrovinyl)-indoles, isatins and chiral polycyclic α-amino acids under catalyst-free conditions at room temperature in EtOH-H2O. The salient features of this methodology are eco-friendliness, high yields and the ease of obtaining target compounds without the involvement of toxic solvents and column chromatography. These novel polycyclic pyrrolidine-fused spirooxindoles provide a collection of structurally diverse compounds that show promise for future bioassays and medical treatments.

Asymmetrical natural hybridization varies among hybrid swarms between two diploid Rhododendron species.

Background and Aims: The extent to which hybridization leads to gene flow between plant species depends on the structure of hybrid populations. However, if this varies between locations, species barriers might prove permeable in some locations but not in others. To assess possible variation in hybrid population structure, the magnitude and direction of natural hybridization between two Chinese endemic species, Rhododendron spiciferum and Rhododendron spinuliferum , were evaluated. Methods: Thirteen nuclear microsatellite markers were employed to characterize 566 individuals collected from 15 non-allopatric populations and nine allopatric parental populations. Chloroplast DNA (cpDNA) sequences were obtained from a subset of samples. Genetic structure and direction of gene flow was determined using a combination of STRUCTURE and NEWHYBRIDS analysis. Key Results: Nuclear analysis revealed that parental taxa formed two genetically distinct clusters and hybrids shared the genetic background of both parents and did not form a separate genetic lineage. Overall, hybrid swarms were dominated by early- and later-generation hybrids, with a significantly higher proportion of hybrids (59·6 %) possessing >50 % R. spiciferum-like nuclear germplasm. The cpDNA analysis further indicated that a significantly greater proportion of hybrids (61·1 %) possessed the R. spiciferum cpDNA haplotype. Conclusions: Gene flow between R. spiciferum and R. spinuliferum was found to be bidirectional in 14 of the 15 hybrid swarms and asymmetrical in six hybrid swarms. Asymmetrical gene flow was evident for only nuclear DNA (nDNA) in two populations, for only cpDNA in three populations, and for both nDNA and cpDNA in one population. Collectively, the variation in genetic structure found among the 15 hybrid swarms suggests that introgression rather than hybrid speciation is a more likely outcome of hybridization between these hybridizing taxa.

Research progress of hydroxychloroquine and autophagy inhibitors on cancer.

PURPOSE: Hydroxychloroquine (HCQ), the analog of chloroquine, augments the effect of chemotherapies and radiotherapy on various tumors identified in the current clinical trials. Meanwhile, the toxicity of HCQ retinopathy raises concern worldwide. Thus, the potent autophagy inhibitors are urgently needed. METHODS: A systematic review was related to 'hydroxychloroquine' or 'chloroquine' with 'clinical trials,' 'retinopathy' and 'new autophagy inhibitors.' This led to many cross-references involving HCQ, and these data have been incorporated into the following study. RESULTS: Many preclinical studies indicate that the combination of HCQ with chemotherapies or radiotherapies may enhance the effect of anticancer, providing base for launching cancer clinical trials involving HCQ. The new and more sensitive diagnostic techniques report a prevalence of HCQ retinopathy up to 7.5%. Lys05, SAR405, verteporfin, VATG-027, mefloquine and spautin-1 may be potent autophagy inhibitors. CONCLUSION: Additional mechanistic studies of HCQ in preclinical models are still required in order to answer these questions whether HCQ actually inhibits autophagy in non-selective tumors and whether the extent of inhibition would be sufficient to alter chemotherapy or radiotherapy sensitivity.

Application of Carbon-Microsphere-Modified Electrodes for Electrochemistry of Hemoglobin and Electrocatalytic Sensing of Trichloroacetic Acid.

By using the hydrothermal method, carbon microspheres (CMS) were fabricated and used for electrode modification. The characteristics of CMS were investigated using various techniques. The biocompatible sensing platform was built by immobilizing hemoglobin (Hb) on the micrometer-sized CMS-modified electrode with a layer of chitosan membrane. On the cyclic voltammogram, a couple of quasi-reversible cathodic and anodic peaks appeared, showing that direct electrochemistry of Hb with the working electrode was achieved. The catalytic reduction peak currents of the bioelectrode to trichloroacetic acid was established in the linear range of 2.0~70.0 mmol·L(-1) accompanied by a detection limit of 0.30 mmol·L(-1) (3σ). The modified electrode displayed favorable sensitivity, good reproducibility and stability, which suggests that CMS is promising for fabricating third-generation bioelectrochemical sensors.