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Pantetheinase is an enzyme that catalyzes the hydrolysis of pantetheine, releasing pantothenic acid (vitamin B5) and cysteamine as byproducts, which is associated with many physiological and pathological processes. In this work, a two-photon fluorescent probe PA-BAN for pantetheinase based on N-butyl-4-amino-1,8-naphthalimide fluorophore scaffold, was designed, synthesized, and developed for sensing the pantetheinase activity in various scenarios. In consideration of the catalytic characteristics and substrate preference of pantetheinase, we selected pantothenic acid (PA) as the recognition group and conjugated it to the fluorophore through amidation reaction. The fluorescence intensity of PA-BAN displayed an ideal linear correlation with the concentration of pantetheinase in vitro , with a detection limit of 0.18 ng/mL. PA-BAN also performed well for the visualizing of pantetheinase in live cells, zebrafish, and tissue slices. Moreover, given the pivotal role of pantetheinase in the host's resistance to malaria infection, PA-BAN was utilized to assess the serum pantetheinase activity of Plasmodium -infected mice. We observed a potential link between serum pantetheinase levels and infection severity, especially concerning cerebral malaria (CM) in the experiments of mice. Low serum pantetheinase levels potentially indicate high susceptibility to CM, making it serve as risk factor for individuals infected with malaria. Thus, the utility of PA-BAN in measuring serum pantetheinase levels could add to current diagnostic toolkit for malaria infection, contributing to a more comprehensive assessment of malaria infection. [Display omitted] • A two-photon fluorescent probe displaying notable sensitivity, selectivity, and ideal optical properties. • Fluorescence imaging capability in living cells, zebrafish, and deep tissue. • Addition to existing diagnostic toolkit for malaria infection, facilitating comprehensive assessment of the infection. • Potential association between serum pantetheinase levels and malaria infection severity, particularly cerebral malaria. [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]

• Plasmodium yoelii can repair CRISPR/Cas9-generated DNA breaks by microhomology-mediated end joining. • Size mutants of the central repeat in circumsporozoite surface protein (CSP) were successfully generated. • A minimum size of the CSP central repeat region is required for mosquito stage development. CRISPR/Cas9 is a powerful genome editing method that has greatly facilitated functional studies in many eukaryotic organisms including malaria parasites. Due to the lack of genes encoding enzymes necessary for the non-homologous end joining DNA repair pathway, genetic manipulation of malaria parasite genomes is generally accomplished through homologous recombination requiring the presence of DNA templates. Recently, an alternative double-strand break repair pathway, microhomology-mediated end joining, was found in the Plasmodium falciparum parasite. Taking advantage of the MMEJ pathway, we developed a MMEJ-based CRISPR/Cas9 (mCRISPR) strategy to efficiently generate multiple mutant parasites simultaneously in genes with repetitive sequences. As a proof of principle, we successfully produced various size mutants in the central repeat region of the Plasmodium yoelii circumsporozoite surface protein without the use of template DNA. Monitoring mixed parasite populations and individual parasites with different sizes of CSP-CRR showed that the CSP-CRR plays a role in the development of mosquito stages, with severe developmental defects in parasites with large deletions in the repeat region. However, the majority of the csp mutant parasite clones grew similarly to the wild type P. yoelii 17XL parasite in mice. This study develops a useful technique to efficiently generate mutant parasites with deletions or insertions, and shows that the CSP-CRR plays a role in parasite development in mosquito. [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]

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]

[Display omitted] • SLA 3D printing technology tailored the electrolyte interface to improve the cell performance. • Multi-physical field modeling was applied to explore the mechanism of the concavo-convex cell to increase the cell performance. • Mathematical model of the cell performance and parameters caused by the electrolyte structure was developed. • Structure design of electrolyte surface enhances the SOFC performance by both effective contact area and ion transfer path length. • Concavo-convex cell showed superior performance than planar cell. Patterned electrolyte surfaces are considered an effective strategy to enhance the cell performance of solid oxide fuel cells by increasing the contact area between the electrode and electrolyte, and subsequently reducing the area specific resistance. In this study, the patterning of an 8 mol% yttria stabilised zirconia (8YSZ) electrolyte surface tailored using the stereolithography (SLA) 3D printing technology and the effects of the electrolyte surface geometry on the cell performance were investigated using multi-physical field simulation and quantitative analysis. Defect-free densified planar and concavo–convex electrolytes were successfully prepared by applying SLA, and the concavo–convex cell yielded a maximum output power density of 288.9 mW cm−2 at 850 °C, which was 46.2 % higher than that of the planar cell. The simulation results revealed significant consumption of reactants and strong electrochemical reactions at the concave surface. Moreover, the hydrogen and oxygen consumptions at the edges were greater than those at the centre of both the concave and convex surfaces, whereas the edges of the concavo–convex structure were more conducive to the electrochemical reaction. Finally, the quantitative correlation between cell performance and the influencing factors was obtained by conducting stepwise linear regression analysis. Reducing the ion transfer path length and providing a sufficiently large effective contact area proved to be a productive strategy for improving cell output performance. [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]

A tetraphenyl ethylene-based zinc complex with strong fluorescence properties and good water stability has been elaborately designed and synthesized. The complex is very sensitive to Fe3+ and Al3+ ions in water with detection limits of 0.31 μM and 0.913 μM, respectively. • A tetraphenyl ethylene-based zinc complex was designed and synthesized. • The complex can be used as an excellent fluorescence probe to detect Fe3+ and Al3+. • Compared with other reported complexes, this probe has a lower detection limit. The application of metal complexes as fluorescent sensor materials has attracted great attention. In this work, we designed and synthesized a tetraphenyl ethylene-based zinc complex {[ZnLCl]·H 2 O} n (1), which not only has excellent water stability, but also shows good photoluminescence behavior. These properties endow 1 a good fluorescence detection ability to metal ions. The experimental results also confirm that the fluorescence behavior of 1 can be quenched by Fe3+ or Al3+ rapidly and sensitively. When other metal ions coexist with Fe3+ or Al3+, 1 can still effectively recognize Fe3+ or Al3+. It means that 1 is a potential fluorescent sensor material with super anti-interference ability to detect Fe3+ or Al3+. The reason is that there are weak interactions between Fe3+/Al3+ and oxygen atoms in 1. Since there's the competitive absorption between Fe3+ and 1 , the quenching effect coefficient of Fe3+ is larger than that of Al3+ and the quenching effect is better than that of Al3+. [ABSTRACT FROM AUTHOR]

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]

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]

3D printing has revolutionized solid oxide fuel cell (SOFC) by introducing complicated structure and new functionalities that cannot be realized using traditional preparation process. This work provides guide and insights into the application of direct-writing 3D printing to fabricate the patterned electrolyte|electrode interface for the anode-supported SOFC using 3 mol % yttria-stabilized zirconia-nickel oxide (3YSZ-NiO) as the anode substrate material. The parameters that affected the shaping and performance of SOFC including the rheological properties of 3YSZ-NiO anode paste, the printing parameters, and the heat treatment process of the pre-sintered anode substrate were evaluated. The prepared 3YSZ-NiO paste exhibited a typical shear-thinning characteristic, "yielding" solid-like behavior, and time- and temperature-independent stability performance, which ensured the paste suitable for extrusion while allowing the shape of the printed body to be maintained after extrusion during the direct-writing printing process. The as-prepared anode paste, combined with the obtained values of 0.1 MPa, 100 mm s−1, 100 rpm, and 0.3 mm for printing parameters of the extrusion pressure, the printing speed, the screw speed, and the nozzle diameter, respectively, as well as the devised heat treatment program for the pre-sintered 3YSZ-NiO anode substrate, successfully produced defect-free corrugated anode substrates. The cell made from the as-mentioned anode substrate showed an open circuit voltage of 1.02 V and a maximum power density of 619.44 mW cm−2 at 850 °C, which was comparable to the other identical cells fabricated by traditional and other 3D printing processes. Using the 3D printing process shown here, the preparation time of patterned anode substrate can be reduced and simplified. [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]

Panic disorder (PD), major depressive disorder (MDD), and the comorbidity (PD&MDD) in college students have caused a heavy disease burden for individuals and families. However, little was known for the comorbidity, especially the impact of parental rearing style on the incidence of the PD&MDD comorbidity. A cohort study was conducted among 6652 Chinese college students. Composite International Diagnostic Interview (CIDI-3.0) was used for disease diagnosis. The parental rearing styles were measured by the Egna Minnen Beträffande Uppfostran (EMBU) scale and factor analysis was used to reduce the dimension of the EMBU scale. Multinomial logistic regression models were used to determine the relationships between parenting styles and disease incidence. SPSS version 26.0 was used for all statistical analyses. The 1-year incidence of PD, MDD, and PD&MDD comorbidity was 0.27 %, 2.04 %, and 0.21 %, respectively. Emotional warmth mode (OR = 0.753, 95%CI: 0.631–0.899, P < 0.01) were only negatively correlated with major depressive disorder. However, punishment denial mode (OR = 1.857, 95%CI: 1.316–2.620, P < 0.01) and over-participation mode (OR = 1.862, 95%CI: 1.176–2.949, P < 0.01) were positively correlated with the comorbidity of panic disorder and major depressive disorder. The limited follow-up period was only 1 year in this study which had impacted the collection of new onset cases. Parental rearing style has a long-term influence on the psychiatric status of college students. Parenting style interventions working as the second level of mental disorder prevention will play an important role in MDD, PD and comorbidity prevention. • The 1-year incidence of PD, MDD, and PD&MDD comorbidity in college students was 0.27 %, 2.04 %, and 0.21 %, respectively. • Punishment denial (OR = 1.857) and over-participation (OR = 1.862) modes were positively correlated with PD&MDD comorbidity. • Emotional warmth mode (OR = 0.753) were only negatively correlated with major depressive disorder. [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]

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]

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]

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]

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]

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]

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]

A non-Markovian theory of dissipative many-electron systems in the presence of arbitrary coherent fields is presented. The new formulation is constructed via the second-quantization of a complete second-order quantum dissipation theory followed by the random phase or time-dependent Hartree–Fock approximation for electron–electron correlation. The theory is shown to be of the Fermi–Dirac thermal equilibrium statistics limit if electron–electron correlation is neglected. The key quantity is the reduced single-electron density matrix instead of the reduced density matrix of the system, which leads to the drastic reduction of numerical simulation time. The validity of the dynamic mean-field approximation is tested in a model two-electron spin-conversed system with Ohmic dissipation in the presence of excitation field. [Copyright &y& Elsevier]

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]

Duck Tembusu virus disease, caused by duck Tembusu virus (DTMUV), brings great harm to duck industry. Early diagnosis is of great significance for the prevention and control of this disease. In order to develop a specific and sensitive method for rapid diagnosis of DTMUV, reverse-transcriptase recombinase aided amplification combined with lateral flow dipstick (RT-RAA-LFD) method for detection of DTMUV was established. Firstly, downstream primer was labeled with biotin and probe was labeled with FAM, and primer concentration, reaction time, and reaction temperature were optimized. Then, the specificity and sensitivity of this method was investigated. The results of specificity test showed that it had no cross reaction with other common pathogens such as low pathogenic avian influenza virus (AIV), Newcastle disease virus (NDV), duck hepatitis A virus (DHV), and duck Reovirus. The results of sensitivity test showed that the minimum detection limit of this method was 10 copies/μL, which was 1000 times than conventional RT-PCR (104 copies/μL), and equivalent to that of fluorescent quantitative PCR. Furthermore, this RT-RAA-LFD method demonstrated excellent intragroup and intergroup consistency. Finally, the RT-RAA-LFD assay and real-time PCR were both utilized to examine 58 clinical samples concurrently. The results showed that the RT-RAA-LFD method (5/58) was more sensitive than the fluorescence quantitative PCR method (4/58). In summary, RT-RAA-LFD method established in this study had a strong specificity and high sensitivity, which provided technical support for clinical detection of DTMUV. • A RT-RAA-LFD method for detection of DTMUV was established. • The RT-RAA-LFD is an ideal assay for clinical detection of DTMUV. • The RT-RAA-LFD method is characterized by its straightforward implementation, high accuracy and sensitivity. [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]

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]

Persistent or excess activation of NF-κB leads to cancer, autoimmune and inflammatory diseases. Therefore, activated NF-κB needs to be terminated after induction, which highlights the physiological significance of NF-κB-negative regulators. However, the molecular mechanisms that negatively regulate NF-κB are not well understood. Here, we report that Ring Finger Protein 8 (RNF8), an E3 ubiquitin ligase, inhibits TNFα-mediated NF-κB activation by targeting IκB kinase (IKK). Upon TNFα stimulation, RNF8 binds to the catalytic subunits of IKK complex, resulting in inhibition of IKKα/β phosphorylation and subsequent NF-κB activation. RNF8 targets the IKK complex in a manner independent of its RING domain. We further provide evidence that the silencing of RNF8 results in enhanced TNFα-induced IKK activation, and an increase expression of NF-κB-induced inflammatory cytokine IL-8. Our study identifies a previously unrecognized role for RNF8 in the negative regulation of NF-κB activation by targeting and deactivating the IKK complex. [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]

A highly effective and operationally practical method for the regioselective deuteration of N -alkyl-substituted anilines employing Ru 3 (CO) 12 (⩽1 mol %) as catalyst and D 2 O as deuterium source was described. A variety of N -alkyl-substituted anilines were efficiently deuterated (up to 98%) at the ortho and/or para position with respect to the nitrogen at neutral conditions. Under the present conditions, deuterated anilines can be easily obtained with simple extraction and evaporation. Substituents with aromatic methoxy groups would not influence the selectivity compared to previous method. [ABSTRACT FROM AUTHOR]

Highlights: [•] In this study, we prepared the subunit vaccines of liposome containing gp85 protein of ALV-J. [•] Liposomal vaccines were able to stimulate chickens to produce high level of serum antibody and reduce the presence of viremia effectively. [•] Liposome can enhance immune response of gp85 protein more than Freund's adjuvant. [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]

[Display omitted] • Ferrocene-functionalized NH 2 -Ni-MOF was fabricated by post-synthesis modification. • NH 2 -Ni-MOF nanoplates promote the adsorption and pre-concentration of target metal ions. • The bonded Fc moiety improves the conductivity of MOF and acts as an reference reporter. • Improved reproducibility is obtained via the ratiometric strategy. • Simultaneous electrochemical detection of multiple toxic heavy metal ions is realized. The development of selective electrochemical response materials and new detection strategies are the research focus in the field of heavy metal ion (HMI) electroanalysis. Herein, a Ni(II)-based metal-organic framework (NH 2 -Ni-MOF) was synthesized and functionalized by electrochemically active molecule of ferrocene (Fc) via post-synthesis modification. Based on the Fc-functionalized NH 2 -Ni-MOF (Fc-NH 2 -Ni-MOF), a novel electrochemical ratiometric sensing platform was developed and applied for the simultaneous determination of various HMIs. The prepared NH 2 -Ni-MOF exhibits nanoplate structure, which is conducive to increase accessible electrode area and expose more active sites, thus promoting the adsorption and pre-concentration of HMIs. The modification of Fc on MOF not only enhances the electrical conductivity of the MOF material, but also provides an internal reference signal for the ratiometric analysis. Due to the excellent characteristics of the Fc-NH 2 -Ni-MOF, the as-prepared ratiometric electrochemical sensing platform exhibits wide linear ranges (0.001 μM to 2.0 μM for lead ions (Pb2+), and 0.01 μM to 2.0 μM for copper ions (Cu2+) as well as cadmium ions (Cd2+)) and high sensitivity (the detection limit toward Cu2+, Pb2+ and Cd2+ is 6.3 nM, 0.2 nM and 7.1 nM, respectively). In addition, compared with the non-ratiometric strategy, the reproducibility of ratiometric analysis is significantly improved. The developed electrochemical method with high sensitivity, selectivity and reliability exhibits bright application prospects in the detection of real samples. Moreover, the electrochemical application of MOF materials has been effectively expanded. [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]

• Metabolically stable diphenylamine derivatives are developed. • 7d suppresses prostate cancer through AR and BET inhibition. • 7d disrupts AR mutants and reduces c-Myc expression. • 7d inhibits AR-V7-positive prostate cancer growth in vitro and in vivo. Androgen receptor (AR) is a crucial driver of prostate cancer (PC). AR-relevant resistance remains a major challenge in castration-resistant prostate cancer (CRPC). Bromodomain and extra-terminal domain (BET) family are critical AR coregulators. Here, we developed several diphenylamine derivatives and identified compound 7d that disrupted the functions of AR and BET family in prostate cancer and exhibited favorable metabolic stability in vitro and high drug exposure in vivo. We showed 7d not only bound to AR, suppressed transactivation of wild-type AR (wt-AR) and the mutant that mediates Enzalutamide resistance, but also reduced c-Myc protein expression through BET inhibition. In addition, 7d inhibited the proliferation of AR-positive PC cells with favorable selectivity and suppressed AR-V7-expressing VCaP and 22Rv1 xenografts growth in vivo. Collectively, these results indicate the potential of lead compound 7d as an orally available AR and BET inhibitor to treat CRPC and overcome antiandrogen resistance. [ABSTRACT FROM AUTHOR]

Androgen receptor (AR) has been a target of prostate cancer (PC) for nearly six decades. Recently, downregulating or degrading AR and the mutants especially the splice variant 7 (AR-V7) lacking ligand binding domain (LBD) emerged as an advantageous therapeutic approach to overcome drug resistance. Here, the structural modification of darolutamide resulted in the discovery of dual-action AR inhibitors and down-regulators. Unlike other traditional AR antagonists targeting the AR-LBD, compounds 4k and 4b not only inhibit the activities of wt-AR and AR-F876L mutant but also downregulate the protein expression of full-length (AR-full) and AR variant 7 (AR-V7) at mRNA level. In cell proliferation assays, compounds 4k and 4b exhibited better antiproliferative activities than darolutamide and enzalutamide against AR-V7-positive 22Rv1 cells and VCaP cells. In addition, 4k demonstrated better antitumor activity than clinically used enzalutamide in castration-resistant VCaP xenograft model. Collectively, combining the activities of AR inhibition and downregulation, compound 4k is proposed as an advantageous lead compound to disrupt AR signaling and overcome resistance. Image 1 • 36 compounds deriving from darolutamide were synthesized and evaluated. • Structural modification of darolutamide led to the discovery of dual-action AR inhibitors and down-regulators. • Inhibition of wt-AR and AR-F876L mutant. • Decrease the protein expression of full-length AR and AR-V7 from mRNA level. • Better antitumor activity against castration-resistant VCaP xenograft than enzalutamide. [ABSTRACT FROM AUTHOR]