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Background: Eukaryotic genes contain introns that are removed by the spliceosomal machinery during mRNA maturation. Introns impose a huge energetic burden on a cell; therefore, they must play an essential role in maintaining genome stability and/or regulating gene expression. Many genes (> 50%) in Plasmodium parasites contain predicted introns, including introns in 5′ and 3′ untranslated regions (UTR). However, the roles of UTR introns in the gene expression of malaria parasites remain unknown. Methods: In this study, an episomal dual-luciferase assay was developed to evaluate gene expression driven by promoters with or without a 5′UTR intron from four Plasmodium yoelii genes. To investigate the effect of the 5′UTR intron on endogenous gene expression, the pytctp gene was tagged with 3xHA at the N-terminal of the coding region, and parasites with or without the 5′UTR intron were generated using the CRISPR/Cas9 system. Results: We showed that promoters with 5′UTR introns had higher activities in driving gene expression than those without 5′UTR introns. The results were confirmed in recombinant parasites expressing an HA-tagged gene (pytctp) driven by promoter with or without 5′UTR intron. The enhancement of gene expression was intron size dependent, but not the DNA sequence, e.g. the longer the intron, the higher levels of expression. Similar results were observed when a promoter from one strain of P. yoelii was introduced into different parasite strains. Finally, the 5′UTR introns were alternatively spliced in different parasite development stages, suggesting an active mechanism employed by the parasites to regulate gene expression in various developmental stages. Conclusions: Plasmodium 5′UTR introns enhance gene expression in a size-dependent manner; the presence of alternatively spliced mRNAs in different parasite developmental stages suggests that alternative slicing of 5′UTR introns is one of the key mechanisms in regulating parasite gene expression and differentiation. [ABSTRACT FROM AUTHOR]

Mutations in a Plasmodium de-ubiquitinase UBP1 have been linked to antimalarial drug resistance. However, the UBP1-mediated drug-resistant mechanism remains unknown. Through drug selection, genetic mapping, allelic exchange, and functional characterization, here we show that simultaneous mutations of two amino acids (I1560N and P2874T) in the Plasmodium yoelii UBP1 can mediate high-level resistance to mefloquine, lumefantrine, and piperaquine. Mechanistically, the double mutations are shown to impair UBP1 cytoplasmic aggregation and de-ubiquitinating activity, leading to increased ubiquitination levels and altered protein localization, from the parasite digestive vacuole to the plasma membrane, of the P. yoelii multidrug resistance transporter 1 (MDR1). The MDR1 on the plasma membrane enhances the efflux of substrates/drugs out of the parasite cytoplasm to confer multidrug resistance, which can be reversed by inhibition of MDR1 transport. This study reveals a previously unknown drug-resistant mechanism mediated by UBP1 through altered MDR1 localization and substrate transport direction in a mouse model, providing a new malaria treatment strategy. Here, the authors show that two mutations in the Plasmodium de-ubiquitinase UBP1 alter the ubiquitination level, membrane localization, and ligand transport direction of multidrug resistance transporter 1 (MDR1), leading to multiple drug resistances. [ABSTRACT FROM AUTHOR]

As intrinsically stretchable materials for flexible electronics construction, liquid metal (LM) based composite conductors face challenges to achieve a high conductivity with minimum resistance increase due to the large dimensional change and poor wettability under a large tensile strain. To address this issue, a super-stretchable eutectic gallium indium (EGaIn) foamed elastomer composite is prepared with the assistance of a sugar template and O2 plasma treatment, and displays a marginal resistance change of only ∼31.3% under a large strain of 500% due to the reorientation and elongation of the conductive network. The EGaIn conductor exhibits superior properties of a high uptake of LM and conductivity enhancement from ∼2.38 × 104 (0% strain) to ∼2.97 × 105 S m−1 (500% strain) due to the strong capillary force during stretching. This work is a significant step toward high-performance stretchable conductors, demonstrating great potential in multifunctional device development including self-powered nanogenerators, electromagnetic interface (EMI) shielding, and thermal regulators. [ABSTRACT FROM AUTHOR]

Screening of large and diverse libraries is the 'bread and butter' in the first phase of the discovery of novel drugs. However, maintenance and periodic renewal of high-quality large compound collections pose considerable logistic, environmental and monetary problems. Here, we exercise an alternative, the 'on-the-fly' synthesis of large and diverse libraries on a nanoscale in a highly automated fashion. For the first time, we show the feasibility of the synthesis of a large library based on 16 different chemistries in parallel on several 384-well plates using the acoustic dispensing ejection (ADE) technology platform. In contrast to combinatorial chemistry, we produced 16 scaffolds at the same time and in a sparse matrix fashion, and each compound was produced by a random combination of diverse large building blocks. The synthesis, analytics, resynthesis of selected compounds, and chemoinformatic analysis of the library are described. The advantages of the herein described automated nanoscale synthesis approach include great library diversity, absence of library storage logistics, superior economics, speed of synthesis by automation, increased safety, and hence sustainable chemistry. [ABSTRACT FROM AUTHOR]

The muscle contractions in human epidermis carry abundant information for medical diagnostics and health monitoring. Traditional crack‐based strain sensors possess high mechanosensitivity, but have limited stretchability for human epidermis monitoring. Herein, by coupling the complementary effects of two parallel connected cracked gold (Au) film electrodes and an engineered ordered layer of Ag nanowire micromeshes (Ag NMs), a strain sensor with enhanced extensibility as well as high sensitivity is provided. The Au and Ag NMs sensory layers separated by poly(dimethylsiloxane) (PDMS) matrix can be equal to two resistors in parallel, and the Ag NMs would provide stable alternative current pathways to ensure the efficient electronic transport even at high strains when Au layer totally ruptures. The resultant sensor possesses wide detection range of up to ≈22%, great sensitivity (a gauge factor of 2658.9 within 16% strain, and 11026.7 with strain of 16–20%), quick response and relaxation time (≈180 ms/≈200 ms), and excellent durability (≈1000 stretching–releasing cycles). Various human epidermal signals can be recognized by the sensor, which demonstrate great potential applications in wearable healthcare monitors, electronic skins, and intelligent devices. [ABSTRACT FROM AUTHOR]

To realize high performance flexible transparent electronics with extreme environmental adaptivity, Ag nanowires (Ag NWs) electrodes should simultaneously meet the requirements of high-temperature tolerance, chemical and mechanical robustness. Herein, a scalable Ag NWs bundle micro-meshes embedded in polyimide (Ag BMs/ePI) conducting film via a facile spray coating and transfer method is reported. Due to the synergistic effect of bundle micromesh and embedded architecture, the Ag BMs/ePI electrode exhibits high thermal stability (370 °C and 400 °C under ambient and nitrogen atmosphere conditions, respectively), low sheet resistance variation (<4%), good corrosion and deformation resistance. As an electrical heater, the Ag BMs/ePI can achieve ~204 °C with the fast thermal response time of ~8 s at 8 V, and exhibits good heating stability under bent condition. This work offers a promising platform for the emerging flexible transparent electronics to adapt extreme environments, especially for those devices which require high-temperature processing. [ABSTRACT FROM AUTHOR]

Designing a flexible transparent electronic device with biological functions is of great interest for the future wearable integrated artificial intelligence equipment. Nociceptor is a vitally important receptor of sensory neuron, which is responsible for providing a warning signal by recognizing noxious stimuli to reduce potential physical injury. Here, a flexible transparent artificial nociceptor device is demonstrated to simulate the biological nociceptor functions based on the indium tin oxide (ITO) memristor, which exhibits forming-free and reproducible threshold resistive switching behaviors. This structurally simple memristor can imitate the key features of biological nociceptor, including "threshold," "relaxation," and "no adaptation" behaviors and sensitization phenomena of hyperalgesia and allodynia upon external stimuli. Finally, an alarm system is built to demonstrate the simplicity and feasibility of this artificial nociceptor for future neuromorphic systems. These results indicate a potential application of the ITO memristor in the future flexible invisible neuromorphic cognitive platform. [ABSTRACT FROM AUTHOR]

Background: Malignant melanoma is an aggressive skin cancer and a tumor of melanocytic origin. Recent studies have suggested that long non-coding RNAs (lncRNAs) play crucial regulatory roles in multiple malignancies, including melanoma. Testis expressed 41 (TEX41) is a relatively new lncRNA whose mechanism in melanoma remains vague.Aims: This study aimed to explore the role and specific mechanism of TEX41 in melanoma.Methods: The expression of genes involved in this study was determined by qRT-PCR. Functional assays were conducted to analyze the role of relevant genes in melanoma cells. The interaction between TEX41 promoter and IRF4 as well as the relationship among TEX41, miR-103a-3p and C1QB was verified by mechanism assays.Results: IRF4 up-regulated TEX41 at the transcriptional level in melanoma cells. TEX41 knockdown hindered melanoma cell proliferation, migration and invasion while promoting cell apoptosis. TEX41 bound to miR-103a-3p and regulated C1QB. The suppressive impact of TEX41 depletion on melanoma cell malignant behaviors could be counteracted by miR-103a-3p inhibition or C1QB overexpression. Moreover, IRF4 could facilitate melanoma cell growth via up-regulating C1QB.Conclusions: IRF4-activated TEX41 sequestered miR-103a-3p and modulated C1QB to promote melanoma cell malignant behaviors, for which TEX41 might be regarded as a potential therapeutic target for melanoma. [ABSTRACT FROM AUTHOR]

Quantitative myocardial contrast echocardiography (MCE) has been proved to be valuable in detecting myocardial ischemia. During quantitative MCE analysis, myocardial segmentation is a critical step in determining accurate region of interests (ROIs). However, traditional myocardial segmentation mainly relies on manual tracing of myocardial contours, which is time-consuming and laborious. To solve this problem, we propose a fully automatic myocardial segmentation framework that can segment myocardial regions in MCE accurately without human intervention. A total of 100 patients' MCE sequences were divided into a training set and a test set according to a 7: 3 proportion for analysis. We proposed a bi-directional training schema, which incorporated temporal information of forward and backward direction among frames in MCE sequences to ensure temporal consistency by combining convolutional neural network with recurrent neural network. Experiment results demonstrated that compared with a traditional segmentation model (U-net) and the model considering only forward temporal information (U-net + forward), our framework achieved the highest segmentation precision in Dice coefficient (U-net vs U-net + forward vs our framework: 0.78 ± 0.07 vs 0.79 ± 0.07 vs 0.81 ± 0.07, p < 0.01), Intersection over Union (0.65 ± 0.09 vs 0.66 ± 0.09 vs 0.68 ± 0.09, p < 0.01), and lowest Hausdorff Distance (32.68 ± 14.6 vs 28.69 ± 13.18 vs 27.59 ± 12.82 pixel point, p < 0.01). In the visual grading study, the performance of our framework was the best among these three models (52.47 ± 4.29 vs 54.53 ± 5.10 vs 57.30 ± 4.73, p < 0.01). A case report on a randomly selected subject for perfusion analysis showed that the perfusion parameters generated by using myocardial segmentation of our proposed framework were similar to that of the expert annotation. The proposed framework could generate more precise myocardial segmentation when compared with traditional methods. The perfusion parameters generated by these myocardial segmentations have a good similarity to that of manual annotation, suggesting that it has the potential to be utilized in routine clinical practice. [ABSTRACT FROM AUTHOR]

A 3D Co‐based metal–organic framework (Co‐MOF) with two kinds of large pores filled by free Co2+ ions and ligands was synthesized and characterized. To expand the MOF structure and conductivity, the free Co2+ ions and ligands were exchanged by conductive ionic liquid EtpyBr and photosensitive AgNO3 through single crystal‐to‐single crystal transformation, which produced structure‐changed 3D MOFs Co‐MOF‐Br and Co‐Ag‐MOF, which were characterized by single‐crystal X‐ray diffraction. Incorporating small quantities of doped polyaniline (PANI) with redox activity into the pores could further tune the stability and conductivity of the three MOFs. The PANI/MOFs all show outstanding electrical conductivity (≈10−2 S cm−1), and PANI/Co‐MOF‐Br has the largest p‐type Seebeck coefficient of 66.6 μV K−1. PANI/Co‐MOF‐Br and PANI/Co‐Ag‐MOF have 4 and 15 times higher photocurrent density compared with PANI/Co‐MOF, respectively. This work sheds light on the design of advanced electrically conductive 3D MOFs. [ABSTRACT FROM AUTHOR]

Transparent nonvolatile memory fabricated on flexible substrates is expected to meet the requirement of integrated flexible transparent circuits. Here, a simple route to prepare flexible transparent memristors is presented. Flexible transparent conducting Ag grids with low sheet resistance are self‐assembled on polyethylene terephthalate (PET) substrate, and the WO3 dielectric layer is selectively deposited on the Ag grids via a low‐cost cathodic electrodeposition method under ambient condition. Finally, the Au/WO3/Ag grids/PET device exhibits fair good optical transmittance in the visible region, low operating voltages, fast switching speed, and long retention time against electric and mechanical stimulus. Therefore, a universal approach is demonstrated for flexible transparent memristors application by combining Ag grids electrode with cathodic electrodeposition technology. [ABSTRACT FROM AUTHOR]

Purpose: Recent studies have reported important roles of dopamine receptors in the early development and progression of glioblastoma (GBM). Here, we tested the antitumor activity of a Dopamine receptor D1 (DRD1) agonist, either alone or in combination with temozolomide (TMZ) on GBM cells. Methods: Immunofluorescence, immunohistochemistry and Western blotting were used to detect dopamine receptor expression in primary human GBM tissues. In addition, clinical data of GBM patients downloaded from The Cancer Genome Atlas (TCGA) were analyzed. Image-based tracking analysis of LC3 using a mCherry-eGFP-LC3 plasmid was utilized to monitor autophagic flux. Transmission electron microscopy (TEM) was used to visualize aggregation of autophagosomes/autolysosomes. Finally, DRD1 agonist (SKF83959)-induced inhibition of GBM growth was assessed in vitro and in vivo. Results: Positive DRD1 expression was observed in human GBM tissues and found to be related with a good clinical outcome. DRD1 activation specifically inhibited GBM cell growth and significantly disrupted autophagic flux, which led to tumor cell death. Moreover, we found that DRD1 agonist treatment inhibited auto-lysosomal degradation in GBM cells and that this process was calcium overload dependent and related to inhibition of mammalian target of rapamycin (mTOR). Finally, we found that DRD1 agonist and TMZ co-treatment yielded a synergistic therapeutic effect both in vivo and in vitro. Conclusions: From our data we conclude that DRD1 activation inhibits GBM cell growth and may serve as an alternative avenue for the design of future GBM therapies. [ABSTRACT FROM AUTHOR]

The Zusman equation has been widely used to study the effect of solvent dynamics on electron transfer reactions. However, application of this equation is limited by the classical treatment of the nuclear degrees of freedom. In this paper, we revisit the Zusman equation in the framework of the exact hierarchical equations of motion formalism, and show that a high temperature approximation of the hierarchical theory is equivalent to the Zusman equation in describing electron transfer dynamics. Thus the exact hierarchical formalism naturally extends the Zusman equation to include quantum nuclear dynamics at low temperatures. This new finding has also inspired us to rescale the original hierarchical equations and incorporate a filtering algorithm to efficiently propagate the hierarchical equations. Numerical exact results are also presented for the electron transfer reaction dynamics and rate constant calculations. [ABSTRACT FROM AUTHOR]

The theory of optimal control together with that of transient probe absorption spectroscopy are applied for control and detection of molecular wave packet dynamics in the weak response regime. We obtain a globally optimal pump-dump control field which drives the initial state to the predefined target, focused at the inner-turning point region of the electronic ground state potential. As for the detection, we calculate both the integrated and the dispersed transient pump-dumpprobe absorption signals and adopt the difference detection schemes to reveal the optimally controlled molecular dynamics. [ABSTRACT FROM AUTHOR]

A quantum dissipation theory is constructed with the system-bath interaction being treated rigorously at the second-order cumulant level for both reduced dynamics and initial canonical boundary condition. The theory is valid for arbitrary bath correlation functions and time-dependent external driving fields, and satisfies correlated detailed-balance relation at any temperatures. The general formulation assumes a particularly simple form in driven Brownian oscillator systems in which the correlated driving-dissipation effects can be accounted for exactly in terms of local-field correction. Remarks on a class of widely used phenomenological quantum master equations that neglects the bath dispersion-induced dissipation are also made in contact with the present theory. [ABSTRACT FROM AUTHOR]

By using a rather simple algebraic approach, we revisit and further bridge between two most commonly used quantum dissipation theories, the Bloch-Redfield theory and a class of Fokker-Planck equations. The nature of the common approximation scheme involving in these two theories is analyzed in detail. While the Bloch-Redfield theory satisfies the detailed-balance relation, we also construct a class of Fokker-Planck equations that satisfy the detailed-balance relation up to the second moments in phase-space. Developed is also a generalized Fokker-Planck equation that preserves the general positivity of the reduced density operator. Both T[sub 1]-relaxation and pure-T[sub 2] dephasing are considered, and their temperature dependence is shown to be very different. Provided is also an analogy between the quantum pure-T[sub 2] dephasing and the classical heat transport. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Automated, miniaturized and accelerated synthesis for efficient property optimization is a formidable challenge in chemistry in the 21st century as it helps to reduce resources and waste and can deliver products in shorter time frames. Here, we used for the first time acoustic droplet ejection (ADE) technology and fast quality control to screen the efficiency of synthetic reactions on a nanomole scale in an automated and miniaturized fashion. The interrupted Fischer indole combined with Ugi-type reactions yielded several attractive drug-like scaffolds. In 384-well plates, a diverse set of interrupted Fischer indole intermediates were produced and reacted with the tricyclic hydantoin backbone in a 2-step sequence. Similarly, preformed Fischer indole intermediates were used to produce diverse sets of Ugi products and the efficiency was compared with that of the in situ method. Multiple reactions were performed again on a preparative millimole scale, showing scalability from nano to mg and thus synthetic utility. An unprecedented large number of building blocks were used for fast scope and limitation studies (68 isocyanides, 72 carboxylic acids). Miniaturization and analysis of the generated big synthesis data enabled deeper exploration of the chemical space and permitted the gain of knowledge that was previously impractical or impossible, such as the rapid survey of reactions, and building block and functional group compatibility. [ABSTRACT FROM AUTHOR]

We review how the hyperspectral dark field analysis gives us quantitative insights into the manner that different nanoscale materials interact with their environment and how this relationship is directly expressed in an optical readout. We engage classification tools to identify dominant spectral signatures within a scene or to qualitatively characterize nanoparticles individually or in populations based on their composition and morphology. Moreover, we follow up the morphological evolution of nanoparticles over time and in different biological environments to better understand and establish a link between the observed nanoparticles’ changes and cellular behaviors. [ABSTRACT FROM AUTHOR]

A series of thiazole-based inhibitors selectively targeting DNA-binding domain of the androgen receptor (AR) were synthesized and evaluated, and the SAR data were summarized. We identified a novel compound SKLB-C2807 that effectively inhibited the human prostate cancer cell line LNCaP/AR with the IC50 value of 0.38 μ m without significant antiproliferative effects on other cell lines PC-3 (AR-negative), SW620, MCF-7 (ER-positive), and L-O2 (non-cancerous). This compound also considerably decreased the expression of prostate-specific antigen. Its binding mode to the AR-DBD was studied. These efforts lay the foundation for developing the next generation of anti-androgens. [ABSTRACT FROM AUTHOR]

Correction for "Chemistry at the speed of sound': automated 1536-well nanoscale synthesis of 16 scaffolds in parallel' by Li Gao et al., Green Chem., 2023, 25, 1380–1394, https://doi.org/10.1039/D2GC04312B. [ABSTRACT FROM AUTHOR]

Leucocytozoon parasites infect many species of avian hosts, including domestic chicken, and can inflict heavy economic loss on the poultry industry. Two major species of Leucocytozoon parasites have been reported in China, L. sabrazesi and L. caulleryi, although L. sabrazesi appears to be more widespread than L. caulleryi in southern China. The traditional method for detecting Leucocytozoon infection is microscopic examination of blood smears for the presence of mature gametocytes in circulation, which may miss infections with low parasitemia (gametocytemia) or immature gametocytes. Here we developed a PCR-based method to monitor L. sabrazesi infections at seven sites in four provinces of China after testing two PCR primer pairs based on parasite mitochondrial cytochrome b (cytb) and cytochrome c oxidase III (coxIII) genes. We compared the results of PCR detection with those of microscopic observation. As expected, the PCR assays were more sensitive than microscope examination in detecting L. sabrazesi infection and were able to detect parasite DNA after gametocytes disappeared in the blood stream. Using these methods, we investigated monthly dynamics of L. sabrazesi in chickens from a free-range farm in Xiamen, Fujian province of China, over one year. Our results showed that chickens were infected with L. sabrazesi year-round in southern China. Finally, we tested several compounds for potential treatment of Leucocytozoon infections, including primaquine, ketotifen, clomipramine hydrochloride, desipramine hydrochloride, sulfaquinoxaline, and pyrimethamine. Only primaquine had activity against L. sabrazesi gametocytes. Our results provide important information for controlling parasite transmission in southern China and disease management. [ABSTRACT FROM AUTHOR]

Ribosomal protein s15a (RPS15A), a highly conserved cytoplasmic protein, promotes mRNA/ribosome interaction in translation. Recent evidence showed that RPS15A is essential for tumor growth. RPS15A expression level was measured in glioblastoma tissue samples and normal brain (NB) tissue samples. RPS15A RNAi stable cell line U87 and U251 was generated by the pLVTHM-GFP lentiviral RNAi expression system. The knockdown efficiency was confirmed by quantitative real-time PCR and western blot. Molecular mechanisms and the effect of RPS15A on cell growth and migration were investigated by using western blot, MTT assay, wound healing assay, transwell migration assay, and tumorigenesis in nude mice. Here, we report that RPS15A is overexpressed in human glioblastoma tumor tissues. RPS15A knockdown inhibits proliferation and migration of glioblastoma cells in vitro. Knocking down RPS15A leads to the level of p-Akt decrease and cell cycle arrested in G0/G1 phase in U87 and U251 cells. Furthermore, the growth of glioblastoma cell-transplanted tumors in nude mice is inhibited by transduction with Lv-shRPS15A. Our findings indicate that RPS15A promotes cell proliferation and migration in glioblastoma for the first time. RPS15A might play a distinct role in glioblastoma and serve as a potential target for therapy. [ABSTRACT FROM AUTHOR]

Key message: A dominantly inherited major-effect QTL for powdery mildew resistance in cucumber was fine mapped. Two tandemly arrayed cysteine-rich receptor-like protein kinase genes were identified as the most possible candidates. Abstract: Powdery mildew (PM) is one of the most severe fungal diseases of cucumber ( Cucumis sativus L.) and other cucurbit crops, but the molecular genetic mechanisms of powdery mildew resistance in cucurbits are still poorly understood. In this study, through marker-assisted backcrossing with an elite cucumber inbred line, D8 (PM susceptible), we developed a single-segment substitution line, SSSL0.7, carrying 95 kb fragment from PM resistance donor, Jin5-508, that was defined by two microsatellite markers, SSR16472 and SSR16881. A segregating population with 3600 F plants was developed from the SSSL0.7 × D8 mating; segregation analysis confirmed a dominantly inherited major-effect QTL, Pm1.1 in cucumber chromosome 1 underlying PM resistance in SSSL0.7. New molecular markers were developed through exploring the next generation resequenced genomes of Jin5-508 and D8. Linkage analysis and QTL mapping in a subset of the F plants delimited the Pm1.1 locus into a 41.1 kb region, in which eight genes were predicted. Comparative gene expression analysis revealed that two concatenated genes, Csa1M064780 and Csa1M064790 encoding the same function of a cysteine-rich receptor-like protein kinase, were the most likely candidate genes. GFP fusion protein-aided subcellular localization indicated that both candidate genes were located in the plasma membrane, but Csa1M064780 was also found in the nucleus. This is the first report of dominantly inherited PM resistance in cucumber. Results of this study will provide new insights into understanding the phenotypic and genetic mechanisms of PM resistance in cucumber. This work should also facilitate marker-assisted selection in cucumber breeding for PM resistance. [ABSTRACT FROM AUTHOR]

Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and member of the Picornaviridae family. An effective live-attenuated poliovirus vaccine strain (Sabin 1) has been developed and has protected humans from polio. However, a few cases of vaccine virulence reversion have been documented in several countries. For instance, circulating type 1 vaccine-derived poliovirus is a highly pathogenic poliovirus that evolved from an avirulent strain, but the mechanism by which vaccine strains undergo reversion remains unclear. In this study, vaccine strains exhibited A to G/U to C and G to A/C to U hypermutations in the reversed evolution of Sabin 1. Furthermore, the mutation ratios of U to C and C to U were higher than those of other mutation types. Dinucleotide editing context was then analyzed. Results showed that A to G and U to C mutations exhibited preferences similar to adenosine deaminases acting on RNA (ADAR). Hence, ADARs may participate in poliovirus vaccine evolution. [ABSTRACT FROM AUTHOR]

Leucocytozoon parasites infect a large number of avian hosts, including domestic chicken, and cause significant economical loss to the poultry industry. Although the transmission stages of the parasites were observed in avian blood cells more than a century ago, the specific host cell type(s) that the gametocytes infect remain uncertain. Because all the avian blood cells, including red blood cells (RBCs), are nucleated, and the developing parasites dramatically change the morphology of the infected host cells, it has been difficult to identify Leucocytozoon infected host cell(s). Here we use cell-type specific antibodies to investigate the identities of the host cells infected by Leucocytozoon sabrazesi gametocytes. Anti-RBC antibodies stained RBCs membrane strongly, but not the parasite-infected cells, ruling out the possibility of RBCs being the infected host cells. Antibodies recognizing various leukocytes including heterophils, monocytes, lymphocytes, and macrophages did not stain the infected cells either. Antisera raised against a peptide of the parasite cytochrome B (CYTB) stained parasite-infected cells and some leukocytes, particularly cells with a single round nucleus as well as clear/pale cytoplasm suggestive of thrombocytes. Finally, a monoclonal antibody known to specifically bind chicken thrombocytes also stained the infected cells, confirming that L. sabrazesi gametocytes develop within chicken thrombocytes. The identification of L. sabrazesi infected host cell solves a long unresolved puzzle and provides important information for studying parasite invasion of host cells and for developing reagents to interrupt parasite transmission. [ABSTRACT FROM AUTHOR]

Nintedanib is a novel triple angiokinase inhibitor that inhibits three growth factors simultaneously. Deuterated derivatives of nintedanib at certain metabolically active sites were prepared and evaluated in vitro and in vivo. In particular, deuterated compound SKLB-C2202 had significantly improved pharmacokinetic properties compared with nintedanib. These efforts lay the foundation for further investigating the druggability of SKLB-C2202. [ABSTRACT FROM AUTHOR]

A highly effective and operationally simple method for the deuteration of phenols using NaOH as a catalyst and D2O as the deuterium source is presented. A high regioselectivity for the ortho and/or para hydrogens relative to the oxygen atom was achieved, as well as a high degree of deuterium incorporation. The method also has a high functional-group tolerance, and allowed the deuteration of complex pharmaceutically interesting substrates. [ABSTRACT FROM AUTHOR]

Highlights: [•] Isolation of two double bond reductase (DBR) genes from liverworts. [•] These two DBRs showed different substrate preference and catalytic efficiency. [•] A single amino acid enhances the catalytic efficiency of DBR2 versus DBR1. [ABSTRACT FROM AUTHOR]

A magnetic nanocomposite, consisting of Fe3O4 nanoparticles embedded into a Mg/Al layered double hydroxide (LDH) matrix, was developed for cancer multimodal therapy, based on the combination of local magnetic hyperthermia and thermally induced drug delivery. The synthesis procedure involves the sequential hydrolysis of iron salts (Fe2+, Fe3+) and Mg2+/Al3+ nitrates in a carbonate-rich mild alkaline environment followed by the loading of 5-fluorouracil, an anionic anticancer drug, in the interlayer LDH space. Magnetite nanoparticles with a diameter around 30 nm, dispersed in water, constitute the hyperthermia-active phase able to generate a specific loss of power of around 500 W/g-Fe in an alternating current (AC) magnetic field of 24 kA/m and 300 kHz as determined by AC magnetometry and calorimetric measurements. Heat transfer was found to trigger a very rapid release of drug which reached 80% of the loaded mass within 10 min exposure to the applied field. The potential of the Fe3O4/LDH nanocomposites as cancer treatment agents with minimum side-effects, owing to the exclusive presence of inorganic phases, was validated by cell internalization and toxicity assays. [ABSTRACT FROM AUTHOR]

Cutaneous dirt‐adherent disease (CDAD) is a rare psychogenic dermatosis mainly occurring in young Japanese and Chinese women. It mainly occurs on cheeks, forehead, nipple, mammary areola and around mammary areola. To our knowledge, this is the first case of CDAD with the skin lesion of psoriasis rupioides to be reported. In our case, the patient, a 43‐year‐old Chinese man presented with thick, yellowish‐brown adherent crusts on his face with severe painful 6‐days duration. Histopathologic image: Parakeratosis, the epidermis demonstrates regular acanthosis with some thinning of the suprapapillary plates, neutrophils exocytosis are noted. As for the histopathologic diagnosis in his right crus, combined with the clinical manifestation of rupioides‐shaped crusts, film phenomenon and Auspitz's sign, we considered Psoriasis rupioide. [ABSTRACT FROM AUTHOR]