Explore the vast range of titles available.

Chemoresistance to platinum therapy is a major obstacle that needs to be overcome in the treatment of ovarian cancer patients. The high rates and patterns of therapeutic failure seen in patients are consistent with a steady accumulation of drug-resistant cancer stem cells (CSCs). This study demonstrates that the Notch signaling pathway and Notch3 in particular are critical for the regulation of CSCs and tumor resistance to platinum. We show that Notch3 overexpression in tumor cells results in expansion of CSCs and increased platinum chemoresistance. In contrast, γ-secretase inhibitor (GSI), a Notch pathway inhibitor, depletes CSCs and increases tumor sensitivity to platinum. Similarly, a Notch3 siRNA knockdown increases the response to platinum therapy, further demonstrating that modulation of tumor chemosensitivity by GSI is Notch specific. Most importantly, the cisplatin/GSI combination is the only treatment that effectively eliminates both CSCs and the bulk of tumor cells, indicating that a dual combination targeting both populations is needed for tumor eradication. In addition, we found that the cisplatin/GSI combination therapy has a synergistic cytotoxic effect in Notch-dependent tumor cells by enhancing the DNA-damage response, G ₂/M cell-cycle arrest, and apoptosis. Based on these results, we conclude that targeting the Notch pathway could significantly increase tumor sensitivity to platinum therapy. Our study suggests important clinical applications for targeting Notch as part of novel treatment strategies upon diagnosis of ovarian cancer and at recurrence. Both platinum-resistant and platinum-sensitive relapses may benefit from such an approach as clinical data suggest that all relapses after platinum therapy are increasingly platinum resistant.

The Target of Rapamycin complex 1 (TORC1) is a central regulator of eukaryotic cell growth that is inhibited by the drug rapamycin. In the budding yeast Saccharomyces cerevisiae, translational defects associated with TORC1 inactivation inhibit cell cycle progression at an early stage in G1, but little is known about the possible roles for TORC1 later in the cell cycle. We investigated the rapamycin-hypersensitivity phenotype of cells lacking the S phase cyclin Clb5 (clb5Δ) as a basis for uncovering novel connections between TORC1 and the cell cycle regulatory machinery. Dosage suppression experiments suggested that the clb5Δ rapamycin hypersensitivity reflects a unique Clb5-associated cyclin-dependent kinase (CDK) function that cannot be performed by mitotic cyclins and that also involves motor proteins, particularly the kinesin-like protein Kip3. Synchronized cell experiments revealed rapamycin-induced defects in pre-anaphase spindle assembly and S phase progression that were more severe in clb5Δ than in wild-type cells but no apparent activation of Rad53-dependent checkpoint pathways. Some rapamycin-treated cells had aberrant spindle morphologies, but rapamycin did not cause gross defects in the microtubule cytoskeleton. We propose a model in which TORC1 and Clb5/CDK act coordinately to promote both spindle assembly via a pathway involving Kip3 and S phase progression.

We studied sandfly (Diptera: Psychodidae) populations in six provinces of Vietnam. This work explores the diversity of sandfly species according to the province, as well as environment, and updated information on public health since leishmaniasis cases were reported in two provinces. Sandflies were collected using 428 CDC light traps from May 30 to October 13, 2016 and identified based on the morphology of the cibarium, pharynx and/or male genitalia or female spermathecae. A total of 2585 sandflies belonging to five genera and 13 identified species were collected. The main species were: the Sergentomyia barraudi group (12.53%), Se. sylvatica (9.63%) and Phlebotomus stantoni (3.95%). In all, 294 Sergentomyia specimens classified as Se. sp2 and Se. sp3 and a heterogeneous group, herein called Se. und_sp . , showed unknown morphological characteristics requiring further studies. We provide detailed comments about morphological description and taxonomical identification in order to help standardization of sandfly classification in Southeast Asia. We observed differentiation according to the provinces in terms of density and species richness, with Lang Son having the highest density and Ninh Binh having the highest species richness. The majority of specimens were collected in rock caves and outdoors, suggesting mainly cavernicolous and exophilic characters of sandfly species in Northern Vietnam. However, specimens were also collected in intra- and peri-domiciliary sites. It is worth noting that Ph. stantoni was the main species found in dog sheds and indoors, and in particular in a leishmaniasis patient’s house. Nous avons étudié les populations de phlébotomes (Diptera : Psychodidae) dans six provinces du Vietnam. Ce travail explore la diversité des espèces de phlébotomes selon les provinces, les environnements et les informations mises à jour sur la santé publique depuis que des cas de leishmanioses ont été signalés dans deux provinces. Des phlébotomes ont été collectés à l’aide de 428 pièges lumineux CDC du 30 mai au 13 octobre 2016 et identifiés sur la base de la morphologie du cibarium, du pharynx et/ou des organes génitaux des mâles ou des spermathèques des femelles. Au total, 2585 phlébotomes, appartenant à cinq genres et 13 espèces identifiées, ont été collectés. Les principales espèces étaient : le groupe Sergentomyia barraudi (12,53 %), Se. sylvatica (9,63 %) et Phlebotomus stantoni (3,95 %). 294 spécimens de Sergentomyia classés comme Se. sp2 et Se. sp3 et un groupe hétérogène ici appelé Se. und_sp. ont montré des caractéristiques morphologiques inconnues nécessitant des études complémentaires. Nous fournissons des commentaires détaillés sur la description morphologique et l’identification taxonomique afin d’aider à la normalisation de la classification des phlébotomes en Asie du Sud-Est. Nous avons observé une différenciation selon les provinces en termes de densité et de richesse en espèces, avec Lang Son ayant la plus forte densité et Ninh Binh ayant la plus grande richesse en espèces. La majorité des spécimens ont été collectés dans des grottes rocheuses et à l’extérieur, suggérant principalement des caractères cavernicoles et exophiles des espèces de phlébotomes du nord du Vietnam. Cependant, des spécimens ont également été collectés dans des sites intra et péri-domiciliaires. Il convient de noter que Ph. stantoni était la principale espèce trouvée dans les abris pour chiens et à l’intérieur, notamment dans la maison d’un patient atteint de leishmaniose.

In this article, isogeometric analysis (IGA) based on the modified nonlocal couple stress theory (MNCST) is introduced to study bending and free vibration characteristics of functionally graded (FG) nanoplates placed on an elastic foundation (EF). The MNCST is a combination of nonlocal elasticity theory and modified couple stress theory to capture the small-size effects most accurately, hence this theory considers both softening and stiffening effects on responses of FG nanoplates. A higher order refined plate theory is adapted, because it satisfies parabolic distributions of transverse shear stresses across the nanoplate thickness and equals zero at the top and bottom surfaces without requiring shear correction factors. The governing equations are obtained using Hamilton's principle from which deduce the equations determining the natural frequency and displacement of the FG nanoplates. Several comparison studies are conducted to verify the proposed model with other results in the literature. Furthermore, the influence of nonlocal parameters, material length parameters, boundary conditions, material volume exponent on the bending, and free vibration response of FG nanoplates are fully studied.

Ehrlichia canis ( E. canis ) is a tick‐borne, obligate intracellular bacterium that causes canine monocytic ehrlichiosis (CME), a widely distributed infectious disease in dogs with variable clinical severity. While the 16S rRNA gene has been commonly used for detection, limited data are available on the genetic diversity of the immunogenic p28 outer membrane protein gene, particularly in Southeast Asia. Eighty‐three canine blood samples were collected from various districts in Ho Chi Minh City, Vietnam, and screened using polymerase chain reaction (PCR) assays targeting the 16S rRNA and p28 genes. Ten representative p28‐positive samples were selected for Sanger sequencing. Phylogenetic relationships were inferred using the maximum likelihood method. Genetic variability was assessed through nucleotide and amino acid entropy analysis. Of the 83 samples, 40 (48.19%) were positive for both 16S rRNA and p28 genes. Phylogenetic analysis of p28 sequences revealed three major clades, with all Vietnamese strains clustering within clade 3 and showing a 97%–100% nucleotide identity with global references. Entropy analysis identified 50 high‐variability nucleotide sites H ( x ): 0.206–1.013 and 20 amino acid positions H ( x ): 0.206–1.264, including a prominent substitution at position 145 (S ⟶ D/T), suggesting a potential immunogenic variability. This study provides the first detailed molecular characterization of the p28 gene in E. canis from Vietnam, demonstrating both high genetic conservation and localized variation within clade 3. These findings enhance the understanding of regional strain diversity and may inform future diagnostic or vaccine development efforts targeting the p28 protein.

Guava (Psidium guajava L.) is a well-known plant containing high levels of natural antioxidants, the phenolic compounds, which have been employed in numerous cosmetic products. However, these molecules are unstable to oxidants, light, temperature, pH, water, and enzymatic activities. Therefore, to enhance their stability and preserve their antioxidant activity, this study investigated the silk fibroin nanoparticles (SFNs) ability to encapsulate, deliver, and heat-protect the phenolic compounds of the guava leaves ethanolic extract. Firstly, the guava ethanolic extract was produced by maceration, which possessed a total phenolic content of 312.6 mg GAE/g DPW and a high antioxidant activity (IC 50 = 5.397 ± 0.618 µg/mL). Then, the extract loaded SFNs were manufactured by desolvation method, and the particles demonstrated appropriate sizes of 200-700 nm with narrow size distribution, spherical shape, silk-II crystalline structure, high drug entrapment efficiency of > 70% (dependent on the fibroin content), and a two-phase sustained drug release for at least 210 min. Using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, the antioxidant activity of the guava extract was well-preserved in the extract loaded SFNs. Finally, after being treated with high temperature of 70 °C for 24 h, the guava extract almost loses all of its antioxidant property (5 times decrement), whereas the extract loaded SFNs could retain the extract activity. Conclusively, the SFNs proved much potential to deliver and heat-protect the guava extract phenolic compounds, and preserve their antioxidant activity. Confirmed by this case, SFNs could be further explored in protecting other natural compounds from environmental factors.

Background: High circulating neutrophil-lymphocyte ratio (NLR) appears to be prognostic in metastatic colorectal cancer (mCRC). We investigated the relationship of NLR with circulating cytokines and molecular alterations. Methods: We performed retrospective analyses on multiple cohorts of CRC patients (metastatic untreated ( n =166), refractory metastatic ( n =161), hepatectomy ( n =198), stage 2/3 ( n =274), and molecularly screened ( n =342)). High NLR (ratio of absolute neutrophil-to-lymphocyte counts in peripheral blood) was defined as NLR>5. Plasma cytokines were evaluated using multiplex-bead assays. Kaplan–Meier estimates, non-parametric correlation analysis, and hierarchical cluster analyses were used. Results: High NLR was associated with poor prognosis in mCRC (hazard ratio (HR) 1.73; 95% confidence interval (CI):1.03–2.89; P =0.039) independent of known prognostic factors and molecular alterations (KRAS/NRAS/BRAF/PIK3CA/CIMP). High NLR correlated with increased expression of interleukin 6 (IL-6), IL-8, IL-2R α , hepatocyte growth factor, macrophage-colony stimulating factor, and vascular epidermal growth factor in exploratory ( n =39) and validation ( n =166) cohorts. Fourteen additional cytokines correlated with high NLR in the validation cohort. All 20 cytokines fell into three major clusters: inflammatory cytokines, angiogenic cytokines, and epidermal growth factor ligands. In mCRC, composite stratification based on NLR-cytokine score provided enhanced prognostic information (HR 2.09; 95% CI: 1.59–2.76; P <0.001) over and above NLR. Conclusions: High NLR is an independent poor prognostic marker in CRC and correlates with a distinct cytokine profile related to key biological processes involved in carcinogenesis. A composite NLR-cytokine stratification has enhanced prognostic value in mCRC.

In this paper, the synthesis of nickel ferrite and its use for voltammetric determination of uric acid (UA) are presented. Nickel ferrite was synthesized via a hydrothermal process using spherical carbons as hard template followed by calcination at 500 °C. It was found that iron and nickel compositions in nickel ferrite can be controlled by the initial Fe/Ni molar ratio. The stoichiometric nickel ferrite (NiFe2O4) with hollow spherical morphology was obtained from a reaction mixture with Fe/Ni molar ratio of around 1.2–1.5. Glassy carbon electrode modified with nickel ferrite was employed to quantitatively determine UA by different pulse voltammetric method. Under the optimum conditions, the anodic peak current was linearly proportional to UA concentration in the range of 0.398 to 6.761 μM. The detection limit (3σ) was found to be 0.15 μM. The proposed method has been employed to determine UA in human urine samples with acceptable recoveries of 95.15–104.8%. On the other hand, the results obtained from this method were also compared with that from standard HPLC method, showing no statistical difference.

The study aims to make an update on the distribution and ecology of sand flies in the Quang Ninh province, Northern Vietnam, where Leishmania cases were reported in 2001. Seventeen sites were chosen in three districts of the province: Ha Long, Cam Pha, and Hoanh Bo. Phlebotomine sand flies were collected using 68 CDC light traps from May 30 to 3 June 2016. Captured specimens were transferred individually into Eppendorf tubes with 90% ethanol.The sand fly heads and genitalia were removed and were mounted in Euparal after successive different baths. Specimen identification was determined based on the morphology of the cibarium, pharynx, and/or male genitalia or female spermathecae. A total of 416 sand flies (125 females, 283 males) belonging to four genera were collected and 10 sand fly species were identified: Sergentomyia silvatica, Se. barraudi, Se. hivernus, Se. bailyi, Phlebotomus mascomai, Ph. stantoni, Ph. yunshengensis, Ph. betisi, Chinius junlianensis, Idiophlebotomus longiforceps.The Sergentomyia genus prevailed (79.7% of the collected sand flies), followed by the Phlebotomus genus (13.7%), the Chinius genus (6.1%), and the Idiophlebotomus genus (0.8%). Besides these well-defined taxa, five specimens, named sp1, showed unknown morphological characteristics, requiring further study.The majority of sand flies were collected in rock caves suggesting the cavernicolous character of the species in the Quang Ninh province. However, specimens were also collected in intra and peridomiciliary sites in which Ph. stantoni and Se. hivernus were found as the main species. It is worth noting that two Ph. stantoni were found in the house of a patient affected by Leishmania.