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Abstract Background Renal medullary carcinoma (RMC) is a highly aggressive cancer in need of new therapeutic strategies. The neddylation pathway can protect cells from DNA damage induced by the platinum‐based chemotherapy used in RMC. We investigated if neddylation inhibition with pevonedistat will synergistically enhance antitumour effects of platinum‐based chemotherapy in RMC. Methods We evaluated the IC50 concentrations of the neddylation‐activating enzyme inhibitor pevonedistat in vitro in RMC cell lines. Bliss synergy scores were calculated using growth inhibition assays following treatment with varying concentrations of pevonedistat and carboplatin. Protein expression was assessed by western blot and immunofluorescence assays. The efficacy of pevonedistat alone or in combination with platinum‐based chemotherapy was evaluated in vivo in platinum‐naïve and platinum‐experienced patient‐derived xenograft (PDX) models of RMC. Results The RMC cell lines demonstrated IC50 concentrations of pevonedistat below the maximum tolerated dose in humans. When combined with carboplatin, pevonedistat demonstrated a significant in vitro synergistic effect. Treatment with carboplatin alone increased nuclear ERCC1 levels used to repair the interstrand crosslinks induced by platinum salts. Conversely, the addition of pevonedistat to carboplatin led to p53 upregulation resulting in FANCD2 suppression and reduced nuclear ERCC1 levels. The addition of pevonedistat to platinum‐based chemotherapy significantly inhibited tumour growth in both platinum‐naïve and platinum‐experienced PDX models of RMC (p

Introduction: The management of refractory immune thrombocytopenia (ITP) is challenging and difficult. The treatment was mainly comprised of cytotoxic and immunosuppressed drugs that rarely lead to long-term remission but potentially cause severe and dangerous side effects. Our current study is a retrospective clinical analysis of refractory ITP patients who underwent phytotherapy as nutritional supplements. Methods: A retrospective clinical analysis of 15 refractory immune thrombocytopenia (ITP) patients aged 12–64 with ITP history for more than 24 months before the enrollments. All patients presented with low platelet count (< 30 × 109/L) and moderate to severe bleeding symptoms such as extensive petechiae, bruising, epistaxis, prolonged menses, rectal bleeding, and hematuria. The patients underwent supportive phytotherapy as nutritional supplements using herbal extracts with hemostatic, immunomodulating, and platelet function augmenting functions Results: The 6-month retrospective clinical evaluation indicated that phytotherapy might offer an effective and safe solution for controlling bleeding symptoms and improving platelet counts for refractory ITP patients. Moreover, phytotherapy also significantly improved patients' red cell count, hemoglobulin, and liver enzyme levels compared to baseline data. Conclusions: In individual cases and economically disadvantaged regions, investigating and applying an appropriate combination of phytotherapy based on scientific knowledge and traditional folk medical experiences might offer an effective, inexpensive, and safe solution for refractory ITP and other bleeding disorders.

A key barrier to the consistent use of condoms is their negative effect on sexual pleasure. Although sexual pleasure is a primary motivation for engaging in sex and is an integral part of overall sexual health, most programs to improve sexual health operate within a pregnancy and disease-prevention paradigm. A new condom, CSD500 (Futura Medical Developments; Surrey, UK), containing an erectogenic drug was developed for use among healthy couples to improve sexual pleasure by increasing penile firmness, size and erection duration. We conducted a randomized controlled trial to test whether promoting the novel condom CSD500 for improved sexual pleasure is effective in reducing condomless sex compared to the provision of standard condoms with counseling for pregnancy and disease prevention. We randomized 500 adult, heterosexual, monogamous couples in Thanh Hoa province, Vietnam to receive either CSD500 (n = 248) or standard condoms (n = 252). At enrollment and after 2, 4, and 6 months, we interviewed women and sampled vaginal fluid to test for the presence of prostate-specific antigen (PSA), an objective, biological marker of recent semen exposure. We registered the protocol before trial initiation at ClinicalTrials.gov (identifier: NCT02934620). Overall, 11.0% of women were PSA positive at enrollment. The proportion of follow-up visits with PSA-positivity did not differ between the intervention (6.8%) and control arms (6.7%; relative risk, 1.01; 95% confidence interval, 0.66–1.54). Thus, we found no evidence that promoting an erectogenic condom to women in a monogamous, heterosexual relationship in Vietnam reduced their exposure to their partner’s semen. These findings might not hold for other populations, especially those with a higher frequency of condomless sex.

Human embryonic stem cells can be differentiated in vitro into primordial germ cell-like cells (PGCLCs) that resemble early primordial germ cells (PGCs). Here the authors transplant PGCLCs generated from rhesus macaque iPSCs into mouse and rhesus macaque seminiferous tubules, which matures these into late PGCs and spermatogonia-like cells.

Organocatalysis has emerged as a powerful synthetic tool in organic chemistry in the last few decades. Among various classes of organocatalysis, chiral diol-based scaffolds, such as BINOLs, VANOLs, and tartaric acid derivatives, have been widely used to induce enantioselectivity due to the ability of the hydroxyls to coordinate with the Lewis acidic sites of reagents or substrates and create a chiral environment for the transformation. In this review, we will discuss the applications of these diol-based catalysts in different types of reactions, including the scopes of reactions and the modes of catalyst activation. In general, the axially chiral aryl diol BINOL and VANOL derivatives serve as the most competent catalyst for most examples, but examples of exclusive success using other scaffolds, herein, suggests that they should not be overlooked. Lastly, the examples, to date, are mainly from tartrate and biaryl diol catalysts, suggesting that innovation may be available from new diol scaffolds.

After its emergence in Wuhan, China, in late November or early December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus rapidly spread globally. Genome sequencing of SARS-CoV-2 allows the reconstruction of its transmission history, although this is contingent on sampling. We analyzed 453 SARS-CoV-2 genomes collected between 20 February and 15 March 2020 from infected patients in Washington state in the United States. We find that most SARS-CoV-2 infections sampled during this time derive from a single introduction in late January or early February 2020, which subsequently spread locally before active community surveillance was implemented.

A variety of genetic techniques have been devised to determine cell lineage relationships during tissue development. Some of these systems monitor cell lineages spatially and/or temporally without regard to gene expression by the cells, whereas others correlate gene expression with the lineage under study. The GAL4 Technique for Real-time and Clonal Expression (G-TRACE) system allows for rapid, fluorescent protein-based visualization of both current and past GAL4 expression patterns and is therefore amenable to genome-wide expression-based lineage screens. Here we describe the results from such a screen, performed by undergraduate students of the University of California, Los Angeles (UCLA) Undergraduate Research Consortium for Functional Genomics (URCFG) and high school summer scholars as part of a discovery-based education program. The results of the screen, which reveal novel expression-based lineage patterns within the brain, the imaginal disc epithelia, and the hematopoietic lymph gland, have been compiled into the G-TRACE Expression Database (GED), an online resource for use by the Drosophila research community. The impact of this discovery-based research experience on student learning gains was assessed independently and shown to be greater than that of similar programs conducted elsewhere. Furthermore, students participating in the URCFG showed considerably higher STEM retention rates than UCLA STEM students that did not participate in the URCFG, as well as STEM students nationwide.

A major challenge in stem cell differentiation is the availability of bioassays to prove cell types generated in vitro are equivalent to cells in vivo. In the mouse, differentiation of primordial germ cell-like cells (PGCLCs) from pluripotent cells was validated by transplantation, leading to the generation of spermatogenesis and to the birth of offspring. Here we report the use of xenotransplantation (monkey to mouse) and homologous transplantation (monkey to monkey) to validate our in vitro protocol for differentiating male rhesus (r) macaque PGCLCs (rPGCLCs) from induced pluripotent stem cells (riPSCs). Specifically, transplantation of aggregates containing rPGCLCs into mouse and nonhuman primate testicles overcomes a major bottleneck in rPGCLC differentiation. These findings suggest that immature rPGCLCs once transplanted into an adult gonadal niche commit to differentiate towards late rPGCs that initiate epigenetic reprogramming but do not complete the conversion into ENO2-positive spermatogonia.

In this work, CoFe2O4/MnFe2O4 core/shell nanostructures were fabricated using the thermal decomposition method. CoFe2O4 (CFO) nanoparticles with an average size of about 10 nm were used as seeds for the growth of MnFe2O4 particles. X-ray diffraction (XRD) analysis results showed that the fabricated core/shell samples have a single-phase face-centered cubic spinel structure similar to the CoFe2O4 sample but with a larger crystal size. Moreover, transmission electron microscopy (TEM) observations showed that the size of nanoparticles of the core/shell samples increased by 1.0–3.5 nm with respect to that of the CoFe2O4 sample, indicating the formation of the MnFe2O4 shell layer. The magnetic measurement results showed that a thin MnFe2O4 shell existed in the core/shell samples resulting in an increased saturation magnetization (Ms) and a slight decrease in coercivity (Hc) compared to the CFO core sample. In contrast, a thicker shell layer resulted in decreased Ms and Hc values compared to the CFO core sample. The magnetic hysteresis curve measured at a low temperature and high magnetic field showed the difference between the reference mixed sample and the core/shell nanostructured sample. Dynamic light scattering (DLS) analysis showed that the liquid samples had uniform particle sizes and high stability. The liquid samples were tested for toxicity on Hep-G2 cancer cell lines and showed no toxicity on this cell line. The core/shell structured samples exhibited higher specific absorption rate (SAR) values than the individual core sample. Notably, the sample with the thickest shell achieved a SAR of 246.62 W/g, while the relaxation rate (r2) of the sample with the thinnest shell was 43.71 (mM s)−1. These initial results suggest our fabricated CoFe2O4/MnFe2O4 core/shell nanostructures exhibit potential biomedical applications, especially in magnetic hyperthermia treatment and magnetic resonance imaging (MRI) contrast enhancement. [ABSTRACT FROM AUTHOR]

The rise in global temperatures, driven by carbon dioxide emissions, has spurred the construction industry to seek carbon reduction strategies. This study evaluates the environmental benefits of using wood materials in construction by redesigning an existing reinforced concrete (RC) residential building in New Taipei City, Taiwan. Four structural combinations were developed, replacing concrete with timber and steel. Numerical simulations confirmed the feasibility of these systems, and comparisons of embodied carbon, costs, and construction periods were conducted. The proposed hybrid models, which extensively replace concrete with timber and steel for the core, reduced initial embodied carbon by 25.6% compared to the original RC building, though costs increased by 3.9 times. These findings underscore the potential of hybrid timber systems as a sustainable alternative in construction, offering significant carbon reduction benefits for Taiwan while aligning with environmental goals. [ABSTRACT FROM AUTHOR]

Eupatorium odoratum L. (Asteraceae), also known as Siam weed, is widely used to stop bleeding and treat diarrhea. However, studies on the chemical composition and biological properties of essential oil from individuals of this species collected in Dak Lak, Vietnam have not been investigated. The chemical composition of E. odoratum essential oil was analyzed using gas chromatography-mass spectrometry (GC-MS), while the antioxidant and antibacterial capacity of E. odoratum essential oil were evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the agar disc diffusion methods, respectively. Molecular docking was used to study the binding energy between major constituents of the essential oil and Escherichia coli DNA (deoxyribonucleic) gyrase subunit B (GyrB). An essential oil yield of 0.61% was obtained, with 51 compounds identified. Among them, the major constituents were germacrene D (20.59%), caryophyllene oxide (12.10%), estragole (11.01%), caryophyllene (9.52%), geijerene (8.21%), cadinene (5.96%), guaia-6,9-diene (4.49%), 3-ethenylcyclopentene (3.54%), and copaen (3.08%). The antioxidant efficiency of the essential oil was determined, with an IC50 of 5.8 ± 0.3 µg/mL. In the antibacterial test, E. odoratum essential oil demonstrated strong antibacterial activity against E. coli (ATCC 25922), with an inhibition zone of 16.4 ± 0.4 mm and a lowest minimum inhibitory concentration (MIC) value of 4.2 ± 0.5 mg/mL. Molecular docking studies revealed binding energy between the essential oil's major constituents and GyrB ranges of 5.0 to 6.5 kcal/mol, predominantly involving hydrophobic interactions with active site residues. These findings indicate that E. odoratum collected in Dak Lak, Vietnam, possesses a high natural potential for pharmaceutical applications. [ABSTRACT FROM AUTHOR]

In our antioxidant screening of some Vietnamese plant extracts, the CHCl3-soluble fraction from Calotropis gigantea (L.) W.T.Aiton flowers showed moderate DPPH free radical scavenging activity with an IC50 value of 55.8 μg/mL. Thus, a further phytochemical study was carried out to obtain five alkaloids, including a new β-carboline-type alkaloid, caloside H (1). These known compounds were identified as 5-hydroxy-(2-methoxymethyl)pyridine (2), nicotinic acid (3), p-(acetylamino)phenol (4), and thymine (5). These structures were determined based on the NMR spectroscopic analysis. In antioxidant assay, caloside H at concentration of 100 μM showed DPPH radical scavenging capacity with a percentage of inhibition of 40.2%. In addition, a plausible biosynthetic pathway for the formation of caloside H was proposed based on the Schiff base formation and Mannich-like reaction. [ABSTRACT FROM AUTHOR]

The White-lipped Treefrog Zhangixalus pachyproctus Yu, Hui, Hou, Wu, Rao & Yang, 2019 was previously confused with Zhangixalus smaragdinus (Blyth, 1852). Records of Zhangixalus smaragdinus from Yunnan (China), Vietnam and Thailand were recognised as a misidentification and this taxon was subsequently described as a new species, based on morphological and molecular evidence. This species is currently known from southern China, Thailand, Laos and Vietnam. However, knowledge about its natural history and feeding ecology is virtually lacking.We herein report a newly-discovered population of Zhangixalus pachyproctus from Lang Son Province, northern Vietnam. In addition, we provide novel data about the diet of Z. pachyproctus, based on stomach content analyses of 38 individuals (37 males and one female). A total of 26 prey categories with 681 items were found in the stomachs of Z. pachyproctus. The dominant prey items of the species were Orthoptera (Acrididae, Tettigoniidae), Coleoptera (Languriida, Leiodidae, larvae, other Coleoptera), Mantodea (Mantidae) and Blattodea (Blaberidae, Blattidae, other Blattodea). Coleoptera (Coccinellidae, Cupedidae, Elateridae, Languriidae Leiodidae, Tenebrionidae, larvae and other Coleoptera) was the category with the highest frequency of prey items, found in 24 stomachs. The most important (IRI) groups amongst the prey of Z. pachyproctus were Coleoptera (24.52%) and followed by Orthoptera (24.43%), Blattodea (9.12%), Mantidae (8.14%) and Hemiptera (4.05%).

Smart ports, utilizing advanced and hybrid technologies, are gaining increasing attention for application in the maritime industry, with driver assistance and autonomous driving being pivotal in container-terminal operations. This study introduces a novel approach for enhancing object detection and distance estimation, focusing principally on decision support for reach stacker container handlers in port terminals by integrating generative and deep learning models. The EfficientDet model, enriched with integrated k-means clustering, is developed to detect and classify objects using a practical dataset of labeled images based on visual features. Moreover, generative models, specifically the diffusion model and generative adversarial network, are utilized to generate depth scenes for estimating object distances. Experimental results indicate that the proposed approach yields superior object detection and distance estimation outcomes in port terminal operations, characterized by high accuracy and reduced computational cost. The proposed method exhibits potential for application across various industries, including transportation, logistics, and security, where precise object detection and distance estimation are vital for efficient and secure operations.