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Assuming that the measurement and process noise covariances are known, the probability hypothesis density (PHD) filter is effective in real-time multi-target tracking; however, noise covariance is often unknown and time-varying for an actual scene. To solve this problem, a strong tracking PHD filter based on Variational Bayes (VB) approximation is proposed in this paper. The measurement noise covariance is described in the linear system by the inverse Wishart (IW) distribution. Then, the fading factor in the strong tracking principle uses the optimal measurement noise covariance at the previous moment to control the state prediction covariance in real-time. The Gaussian IW (GIW) joint distribution adopts the VB approximation to jointly return the measurement noise covariance and the target state covariance. The simulation results show that, compared with the traditional Gaussian mixture PHD (GM-PHD) and the VB-adaptive PHD, the proposed algorithm has higher tracking accuracy and stronger robustness in a more reasonable calculation time. [ABSTRACT FROM AUTHOR]

Chemical sensing for the sensitive and reliable detection of mercury(II) ions (Hg2+) is of great importance in environmental protection, food safety, and biomedical applications. Due to the bio-enrichment property of Hg2+ in organisms, it is particularly meaningful to develop an effective tool that can in situ and rapidly monitor the level of Hg2+ in living organisms. In this work, we report ligand functionalized gold-silver bimetallic nanoclusters with bright red fluorescence as intracellular probes for imaging Hg2+ in living cells and zebrafish. The bimetallic nanoclusters of DTT-GSH@Au/AgNCs (DG-Au/AgNCs) with strong fluorescence that benefited from the synergistic effect of Au and Ag atoms were obtained through a one-pot synthesis method, incorporating glutathione (GSH) and dithiothreitol (DTT) as the reducers and functionalized ligands. Attractively, the bright red fluorescence of DG-Au/AgNCs could be rapidly and selectively quenched by Hg2+ within 1 min with a very low detection limit of 1.01 nM. Additionally, DG-Au/AgNCs had a great advantage in the detection of Hg2+ in living cells and zebrafish owing to its notably strong red fluorescence at 665 nm, which could avoid effectively auto-fluorescence interference from the organism. Such easily prepared bimetallic fluorescent nanoclusters would be expected to provide a noninvasive and sensitive approach in the detection of heavy metals in situ for environmental protection. [ABSTRACT FROM AUTHOR]

Lymphatic metastasis is one of the important parameters used for predicting prognosis for endometrial cancer (EC). Analysis of miR-26a-5p expression in EC tissues from TCGA data (A, B) Analysis of miR-26a-5p expression in EC tumour tissues and paracancerous tissues from TCGA data, respectively. EC with LN-: endometrial cancer with lymph node negative; EC with LN+: endometrial cancer with lymph node positive. Loss of exosomal miR-26a-5p contributes to endometrial cancer lymphangiogenesis and lymphatic metastasis. [Extracted from the article]

With the increasing penetration level of wind turbine generators (WTGs) integrated into the power system, the WTGs are enforced to aid network and fulfill the low voltage ride through (LVRT) requirements during faults. To enhance LVRT capability of permanent magnet synchronous generator (PMSG)-based WTG connected to the grid, this paper presents a novel coordinated control scheme named overspeed-while-storing control for PMSG-based WTG. The proposed control scheme purely regulates the rotor speed to reduce the input power of the machine-side converter (MSC) during slight voltage sags. Contrarily, when the severe voltage sag occurs, the coordinated control scheme sets the rotor speed at the upper-limit to decrease the input power of the MSC at the greatest extent, while the surplus power is absorbed by the supercapacitor energy storage (SCES) so as to reduce its maximum capacity. Moreover, the specific capacity configuration scheme of SCES is detailed in this paper. The effectiveness of the overspeed-while-storing control in enhancing the LVRT capability is validated under different levels of voltage sags and different fault types in MATLAB/Simulink. [ABSTRACT FROM AUTHOR]

Understanding lysosome-related physiology needs specific lysosome probes to track the biological processes of lysosome in living cells. Here, we report an azacyclo-modified fluorescent probe that has a large Stokes shift, good photostability and negligible cytotoxicity for highly specific labeling of lysosome and autolysosome in living cells. The probes with different kinds of azacyclo groups on parent dye dansyl are screened to show that dansyl-cycleanine (DNS-C) with four nitrogen atoms possesses the best lysosome-localized ability. And DNS-C as a universal tracker exhibits excellent ability for lysosome labeling in different cell lines with high overlap coefficients (≥0.90). Different from a commercially available LysoTracker, the Stokes shift of DNS-C up to 240 nm (λ ex/em = 330/570 nm), is much larger than that of LysoTracker ~20 nm (λ ex/em = 573/595 nm). More importantly, the fluorescence of DNS-C keeps still high brightness after a time-lapsed imaging for 40 min in living cells, implying its remarkable photostability for long-term tracking. In addition, DNS-C can also clearly image the autolysosome, a critical subcellular compartment, forming by the fusion of lysosome with autophagosome in autophagy. These results suggest the promising utility of our probe as a powerful tool to real-time trace physiological processes of lysosomes. Image 1 • The azacyclo-localizing fluorescent probe DNS-C exhibits high specificity for lysosome and autolysosome labeling. • The large Stocks shift ~240 nm can efficiently avoid unwanted self-reabsorption and inner-filter effects. • The DNS-C can serve as a universal tracker for lysosome labeling in different kinds of cells. • The DNS-C exhibits excellent photostablility for long-term tracking the lysosome-related behaviors. [ABSTRACT FROM AUTHOR]

Studies on the third-generation of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) targeting EGFRL858R/T790M mutant remain hotspots, specifically for non-small cell lung cancer (NSCLC). In the current study, a new series of EGFR-TKIs with thieno[3,2- d pyrimidine derivatives(6a - 6r) bearing quinolin-2(1 H)-ones were designed and synthesized, through conformational constrained strategy from the third generation of EGFR-TKI olmutinib. In vitro structure-activity relationship (SAR) studies indicated that compounds 6a , 6l , 6m , 6n and 6o exhibited good selective inhibition to EGFRL858R/T790M (IC 50 ≤ 250 nM) over wild type EGFR (IC 50 > 10000 nM). The observed selectivity of compounds 6l and 6o was also proved by the computational molecular docking and the cellular thermal shift assay. These compounds had good growth inhibitory effect on the four tested cancer cell lines. Specifically, 6o could significantly inhibit the colony formation, wound healing and the expression of p-EGFR and its downstream p-ERK in EGFRL858R/T790M H1975 lung cancer cells. Our findings suggest that the thieno[3,2-d]pyrimidine compounds, especially 6l and 6o , can selectively target the mutant EGFRL858R/T790M in vitro and at cellular level and may serve as the lead compounds for generating new series of the third-generation EGFR-TKIs. The new thieno[3,2-d]pyrimidine compounds, especially 6l and 6o , can efficiently and selectively target the mutant EGFRL858R/T790M in vitro and at cellular level and may serve as the lead compounds for generating new series of the third-generation EGFR-TKIs. Image 1 • Half of thieno[3,2-d]pyrimidine derivatives showed potent selective inhibition on EGFRL858R/T790M in vitro. • Compounds 6l and 6o were specifically targeted to EGFRL858R/T790M. • 6o exhibited good and selective inhibition for H1975, bearing EGFRL858R/T790M than those in A549s, bearing EGFRWT. • 6o remarkably down-regulated the expression of p-EGFR and p-ERK in H1975 cells. [ABSTRACT FROM AUTHOR]

Quantifying the phenotypic features of rare diseases such as inborn errors of immunity (IEI) helps clinicians make diagnoses, classify disorders, and objectify the disease severity at its first presentation as well as during therapy and follow-up. Furthermore, it may allow cross-sectional and cohort comparisons and support treatment decisions such as an evaluation for transplantation. On the basis of a literature review, we provide a descriptive comparison of ten selected scores and measures frequently used in IEI and divide these into three categories: (1) diagnostic tools (for Hyper-IgE syndrome, hemophagocytic lymphohistiocytosis, and Wiskott-Aldrich syndrome), (2) morbidity and disease activity measures (for common variable immune deficiency [CVID], profound combined immune deficiency, CTLA-4 haploinsufficiency, immune deficiency and dysregulation activity [IDDA], IPEX organ impairment, and the autoinflammatory disease activity index), and (3) treatment stratification scores (shown for hypogammaglobulinemia). The depth of preclinical and statistical validations varies among the presented tools, and disease-inherent and user-dependent factors complicate their broader application. To support a comparable, standardized evaluation for prospective monitoring of diseases with immune dysregulation, we propose the IDDA2.1 score (comprising 22 parameters on a 2–5-step scale) as a simple yet comprehensive and powerful tool. Originally developed for use in a retrospective study in LRBA deficiency, this new version may be applied to all IEI with immune dysregulation. Reviewing published aggregate cohort data from hundreds of patients, the IDDA kaleidoscope function is presented for 18 exemplary IEI as an instructive phenotype–pattern visualization tool, and an unsupervised, hierarchically clustered heatmap mathematically confirms similarities and differences in their phenotype expression profiles. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that the high incidence of type 2 diabetes in China is associated with low birth weight and excessive nutrition in adulthood, which occurred during the famine years of the 1950s and 1960s, though the specific molecular mechanisms are unclear. In this study, we proposed a severe maternal caloric restriction during late pregnancy, followed by a post weaning high-fat diet in mice. After weaning, normal and high-fat diets were provided to mice to simulate the dietary pattern of modern society. Methods: The pregnant mice were divided into two groups: normal birth weight (NBW) group and low birth weight (LBW) group. After 3 weeks for weaning, the male offspring mice in the NBW and LBW groups were then randomly divided into four subgroups: NC, NH, LC and LC groups. The offspring mice in the NC, NH, LC and LC groups were respectively fed with normal diet, normal diet, high-fat diet and high-fat diet for 18 weeks. After 18 weeks of dietary intervention, detailed analyses of mRNA and protein expression patterns, signaling pathway activities, and promoter methylation states were conducted for all relevant genes. Results: After dietary intervention for 18 weeks, the expressions of CD36, Fabp4, PPARγ, FAS, and ACC1 in the skeletal muscle tissue of the LH group were significantly increased compared with the LC and NH groups (P < 0.05). The level of p-AMPK/AMPK in the skeletal muscle tissue of the LH group was significantly decreased compared with the LC and NH groups (P < 0.05). CPT1 and PGC-1α protein expressions were up-regulated in the LH group (P < 0.05) compared to the LC group. Additionally, the DNA methylation levels of the PGC-1α and GLUT4 gene promoters in the skeletal muscle of the LH groups were higher than those of the LC and NH groups (P < 0.05). However, PPARγ DNA methylation level in the LH group was lower than those of the LC and NH groups (P < 0.05). Conclusions: LBW combined with high-fat diets may increase insulin resistance and diabetes through regulating the CD36-related Fabp4-PPARγ and AMPK/ACC signaling pathways. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we report a simple sonochemical method to synthesize PbWO4 dendrites without any templates. The obtained products were characterized by X-ray diffraction (XRD) and transmission electron microscopy (TEM). The effect of the pH value, precursor and reaction time on the formation of PbWO4 dendrites was investigated. It is found that the obtained PbWO4 dendrites were composed of clusters of nanorods. It is rational to expect that dendritic structures of other oxides may also be synthesized by this simple method. [Copyright &y& Elsevier]

A novel spiropyran-based colorimetric probe SP-DNP bearing a 2,4-dinitrophenyl group as a PhSH-responsive site was synthesized for the detection of thiophenol based on the ring open/closed isomerization process. Upon the addition of PhSH, the probe SP-DNP displayed a remarkable change in UV–vis spectra with a good linear relationship to concentration of PhSH, and result in apparent color change from purple to colorless that could be easily observed by the naked eye even in the presence of other interfering anions. Probe SP-DNP exhibited specific colorimetric response toward PhSH with very fast response (within 30 s) and high sensitivity (detection limit is 0.55 μM). In addition, the probe showed good selectivity and sensitivity toward PhSH through fluorescence quenching process. The sensing mechanism of the nucleophilic substitution-cyclization process was confirmed by 1H NMR and mass spectroscopic analysis. Moreover, probe SP-DNP could detect PhSH in real water samples. Image 1 • Probe SP-DNP was constructed on basis of thiophenol-induced transform merocyanine to spiropyran isomerization process. • The probe could colorimetric and fluorescent respond toward thiophenol with fast response and high sensitivity. • The probe has been successfully demonstrated in monitoring thiophenol in real water samples. [ABSTRACT FROM AUTHOR]

Dendrobium officinale polysaccharide (DOP) is the main active ingredient of Dendrobium officinale Kimura & Migo , which is a precious traditional Chinese medicine and often used in treatment of hepatitis, diabetes, obesity and rheumatoid arthritis. Aim of the study : DOP exhibits significant hypoglycemic activity, while its mechanism remains unclear. The present study aims to investigate the hypoglycemic mechanisms of DOP based on the glucagon-mediated signaling pathways and the liver glycogen structure, which catalyze hepatic glucose metabolism, and provide new knowledge about the antidiabetic mechanism of DOP and further evidence for its clinical use for diabetes. DOP were obtained from the dry stems of Dendrobium officinale by water extraction and alcohol precipitation method. T2DM mice model was established by high-fat diet combined with streptozotocin. Liver histopathological changes were observed by H&E and PAS straining. Pancreatic histology was studied by H&E staining and immunofluorescence analysis. The levels of glucagon and insulin were detected by Elisa Kit and the hepatic glycogen content was detected by GOPOD. The expressions of the hepatic glycogen-related metabolism enzymes, hepatic gluconeogenesis enzymes, and the related protein in cAMP-PKA and Akt/FoxO1 signaling pathways were detected by western blots. Liver glycogen was extracted from the liver tissues by sucrose density gradient centrifugation, and size exclusion chromatography (SEC) was used to analyze the structure of liver glycogen. DOP could significantly affect the glucagon-mediated signaling pathways, cAMP-PKA and Akt/FoxO1, to further promote hepatic glycogen synthesis, inhibit hepatic glycogen degradation and hepatic gluconeogenesis. Moreover, DOP could reverse the instability of the liver glycogen structure and thus probably suppressed glycogen degradation. Thus, DOP finally would ameliorate hepatic glucose metabolism via glucagon-mediated signaling pathways and modifying liver-glycogen structure in diabetic mice. The hypoglycemic mechanism of DOP might be associated with the regulation of glucagon-mediated hepatic glycogen metabolism and gluconeogenesis, and of liver glycogen structure, contributing to improved hepatic glucose metabolism in diabetic mice. DOP could regulate glucagon-mediated signaling pathways and reverse the instability of liver glycogen structure, contributing to improved hepatic glucose metabolism. Image 1 [ABSTRACT FROM AUTHOR]

A novel fluorescent probe 1 was synthesized for the detection of thiophenol on the basis of a unique thiophenol-mediated substitution-cyclization reaction. The probe 1 displayed 420-fold fluorescence intensity enhancement and highly selective and sensitive response for thiophenol over other competing sulfur species. This probe showed an excellent linear relationship in 10–140 μM and the low detection limit of 29 nM. The recognition mechanism of probe 1 toward PhSH was supported by the NMR spectrum and ESI-MS. Furthermore, the probe 1 was successfully applied for detection of thiophenol in living HepG2 cells. Image 1 • A novel fluorescent probe 1 for thiophenol was constructed on the basis of substitution-cyclization reaction. • Probe 1 features significant fluorescence enhancement up to 420-fold in response to thiophenol in aqueous solution. • This probe showed an excellent and wide linear relationship in 10–140 μM and with a low detection limit of 29 nM. • The probe could detect thiophenol in living cells. [ABSTRACT FROM AUTHOR]

Recently, much work has been put into improving species distribution models, especially for systematic conservation planning for important ecosystems. Understanding fish spawning sites requires a thorough examination of ichthyoplankton. These examinations usually produce sparse counts contaminated by inaccurate detection, making it impossible to directly infer the abundance or occurrence from observational data, which could lead to inaccurate model predictions. A flexible modeling framework for estimating and inference about the abundance of eggs with ensemble models that include the presence/absence and abundance components is described in this study. The generalized linear model, generalized additive model, integrated nested Laplace approximations, and random forest habitat modeling approaches were compared within this framework to those currently being used for fish conservation planning at regional scales. Additionally, the distribution of suitable habitats for small yellow croaker (Larimichthys polyactis) spawning stocks were mapped based on the ensemble model. Furthermore, the promotion ability of ensemble models with different weighting methods was evaluated. The outcomes demonstrated that machine learning algorithms performed better than statistical models, and the geometric weighted ensemble model further increased prediction accuracy. However, there was no significant difference compared to the optimal individual model (p > 0.05). The predicted distributions of the four models can be divided into two groups. The central sea of Jiangsu was recognized as the most suitable area by the GAM with a fixed effect for each year and INLA models, while the GLM was similar to the RF with spatial effect (RF-LL) and demonstrated Haizhou Bay as the most suitable area. The ensemble model discovered several areas of highly suitable habitat that dominated areas in the two groups of models and revealed many finer-scale patterns in the egg distribution. According to the ensemble model, although 5.37% of the area could be suitable habitat, only 0.12% was highly suitable. It is suggested that examining small yellow croaker spawning aggregation areas would benefit from using an ensemble modeling approach to identify and prioritize conservation areas. • Using a multi-models and ensemble algorithm for sparse egg data. • Random forest model outperformed individual base models. • Identify abiotic factors contributed to spawning sites selection. • Proposed the locations and areas for priority protected areas. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that the high incidence of type 2 diabetes in China is associated with low birth weight and excessive nutrition in adulthood, which occurred during the famine years of the 1950s and 1960s, though the specific molecular mechanisms are unclear. In this study, we proposed a severe maternal caloric restriction during late pregnancy, followed by a post weaning high-fat diet in mice. After weaning, normal and high-fat diets were provided to mice to simulate the dietary pattern of modern society. Methods: The pregnant mice were divided into two groups: normal birth weight (NBW) group and low birth weight (LBW) group. After 3 weeks for weaning, the male offspring mice in the NBW and LBW groups were then randomly divided into four subgroups: NC, NH, LC and LC groups. The offspring mice in the NC, NH, LC and LC groups were respectively fed with normal diet, normal diet, high-fat diet and high-fat diet for 18 weeks. After 18 weeks of dietary intervention, detailed analyses of mRNA and protein expression patterns, signaling pathway activities, and promoter methylation states were conducted for all relevant genes. Results: After dietary intervention for 18 weeks, the expressions of CD36, Fabp4, PPARγ, FAS, and ACC1 in the skeletal muscle tissue of the LH group were significantly increased compared with the LC and NH groups (P < 0.05). The level of p-AMPK/AMPK in the skeletal muscle tissue of the LH group was significantly decreased compared with the LC and NH groups (P < 0.05). CPT1 and PGC-1α protein expressions were up-regulated in the LH group (P < 0.05) compared to the LC group. Additionally, the DNA methylation levels of the PGC-1α and GLUT4 gene promoters in the skeletal muscle of the LH groups were higher than those of the LC and NH groups (P < 0.05). However, PPARγ DNA methylation level in the LH group was lower than those of the LC and NH groups (P < 0.05). Conclusions: LBW combined with high-fat diets may increase insulin resistance and diabetes through regulating the CD36-related Fabp4-PPARγ and AMPK/ACC signaling pathways. [ABSTRACT FROM AUTHOR]

A new variational Bayesian‐based adaptive distributed fusion unscented Kalman filter (ADFUKF‐VB) algorithm is proposed for the problem of state estimation in a distributed fusion target tracking system with unknown sensor measurement losses. First, the Bernoulli random variables are introduced as the judgement factors of the measurement losses in each local unscented Kalman filter (UKF) of the distributed fusion target tracking system, and the probability density function (PDF) of the measurement loss probability is modelled as a Beta distribution. Then, the variational Bayesian (VB) approach is used to infer the estimated variables in each local UKF. The measurement losses are judged according to the expectations of the Bernoulli random variables, and three ways are adopted to estimate the state vector based on the obtained judgement results. Finally, the covariance intersection (CI) fusion strategy is used to achieve the fusion of all local state estimates. The simulation results show that the proposed ADFUKF‐VB algorithm can accurately judge whether the measurement is lost and estimate the unknown measurement loss probability, moreover, effectively improve the accuracy of state estimation compared with the existing filtering algorithms with unknown measurement losses. [ABSTRACT FROM AUTHOR]

To improve the accuracy of multiple target tracking in the clutter environment, a new joint probabilistic data association (JPDA) algorithm based on variational Bayesian adaptive moment estimation is proposed. First, considering the existence of measurements, the posterior distribution of the target state in JPDA is composed of two parts of probability weighting, that is, the posterior distribution of the target state that the real measurement exists in the association gate and the posterior distribution of the target state that the real measurement does not exist in the association gate. By combining the conjugate properties of the prior and posterior distributions, the prior distributions of the target state in the two cases are classified to provide more accurate a priori information to filter, so as to improve the accuracy of data association. Second, considering the coupling effect between state estimation and data association process, combined with variational Bayesian inference, the problem of minimizing Kullback–Leibler divergence is transformed into the problem of maximizing the evidence lower bound, thereby effectively measuring the distance between the posterior distribution of target state estimation and the real posterior distribution, so as to improve the accuracy of data association again from the perspective of optimizing nonlinear filter. Finally, the adaptive momentum estimation strategy is introduced to iteratively solve the variable distribution that meets the maximization of the evidence lower bound, and the optimization of the posterior distribution of the target state is completed. Theoretical derivation and simulation experiments are conducted to verify the feasibility and effectiveness of the algorithm. [ABSTRACT FROM AUTHOR]

Gadolinium‐based complex contrast agents (GBCAs), frequently applied in magnetic resonance imaging (MRI), are associated with severe acute anaphylactic shock and incurable nephrogenic systemic fibrosis. Besides, the repeated use of GBCAs may result in the accumulation in various tissues. Given these potential adverse effects, GBCAs have not been well used during pregnancy. Herein, a novel metal‐free T2‐weighted MRI nanoprobe, designated fluorinated small‐sized graphene oxide with optimized fluorine content (LF‐sGO), is developed via graphene oxide materials. By introducing specific polar C─F bonds onto the small‐sized graphene oxide (sGO) skeleton, the prepared nanoprobe exhibits excellent water solubility, as well as superior MRI capabilities, thereby furnishing high‐resolution MRI anatomical information. Furthermore, the free radicals on LF‐sGO stabilized by C─F bonds confer LF‐sGO enrichment in the tumor region, enabling comprehensive imaging capability. The cytotoxicity study in vitro indicates that LF‐sGO has the potential to serve as a biocompatible imaging probe. Moreover, detailed in vivo studies on pregnant mice and zebrafish adequately demonstrate that microinjection of LF‐sGO does not induce dysontogensis and teratogenesis. This study successfully showcases a metal‐free nanoprobe that exhibits exceptional MRI capabilities for the purpose of tumor diagnosis. Notably, this nanoprobe holds promise for safe and effective tumor diagnosis during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Platinum-etoposide chemotherapy combined with immune checkpoint inhibitors (ICIs) has been recommended as the first-line standard treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, the effect of thoracic radiotherapy (TRT) on these patients is still unknown. This study aimed to evaluate the efficacy and safety of TRT for ES-SCLC patients who responded to first-line ICIs and chemotherapy (CHT). Methods: Patients who received 4 to 6 cycles of ICIs and CHT as first-line therapy at three hospitals between 2018 and 2022 were included in the analysis. All patients were divided into two groups based on whether they received TRT as first-line treatment, and propensity score matching (PSM) was performed to ensure that the characteristics of two groups were well-balanced. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoint was toxic effects. Results: A total of 276 patients were included, and the median follow-up time was 22.3 (range, 4.0-53.73) months. After PSM, 197 patients were further analysed, and 99 of whom received TRT. The baseline characteristics were well-balanced between patients in the TRT and non-TRT groups. There were significant differences in PFS between the TRT and non-TRT groups, with the median PFS of 10.76 and 7.63 months, respectively (P = 0.014). Significantly improved OS was observed in the TRT group (21.67 vs. 16.6 months, P = 0.009). In addition, the use of TRT was an independent prognostic factor for PFS and OS of ES-SCLC patients receiving ICIs plus CHT. In terms of safety, no significant increase of any grades adverse event (AE) (P = 0.874) and G3-4 AE (P = 0.909) was observed for patients receiving TRT. Radiation esophagitis, gastrointestinal and hematologic toxicities were the most common AEs in TRT group, which were tolerable. And high-dose radiotherapy was associated with higher incidence of pneumonitis. Conclusion: Addition of TRT showed significant survival benefits and well tolerability in ES-SCLC patients receiving platinum-etoposide CHT and ICIs, which could be a feasible first-line treatment strategy for ES-SCLC patients. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have been recommended as the standard treatment for advanced NSCLC patients without driver‐gene mutations. However, there are different genetic characteristics and biological traits of tumors between non‐East Asian (nEA) and East Asian (EA) patients with NSCLC, which may contribute to differences in the efficacy of ICIs in different ethnic populations. Previous findings regarding differences in the efficacy of ICIs among ethnic groups have been inconsistent. Therefore, we performed a meta‐analysis by collecting published data to investigate the clinical outcomes of ICIs for EA NSCLC patients compared to nEA patients. Methods: Overall survival (OS) and progression‐free survival (PFS) were used to access the difference in survival outcomes between the two populations. Subgroup analyses were performed based on the line of ICIs, the use of ICIs alone or in combination, and the type of ICIs. Results: A total of 9826 NSCLC patients from 21 randomized controlled trials (RCTs) with 4064 EAs were included, which involved PD‐1, PD‐L1, and CTLA‐4 inhibitors. EA NSCLC patients who received ICIs‐based therapy were associated with significantly improved survival benefits in OS (p = 0.02) compared with nEA patients. Subgroup analysis indicated that EA patients receiving first‐line ICIs showed significantly superior OS compared with nEA patients (p = 0.007). Chemo‐ICIs treatment showed significant advantages in terms of OS (p = 0.002) and PFS (p = 0.02) among EA patients compared to nEA patients. In addition, PD‐1 inhibitors were associated with improved OS among both EA patients and nEA patients compared with PD‐L1 inhibitors. Conclusion: EA NSCLC patients who received ICIs‐based therapy were associated with significantly improved survival benefits compared with nEA NSCLC patients. Earlier intervention with ICIs and combination treatment was more recommended for EA NSCLC patients. Moreover, PD‐1 inhibitors are associated with prolonged survival among both EA and nEA patients. [ABSTRACT FROM AUTHOR]

Herpesvirus infection is an orderly, regulated process. Among these viruses, the encapsidation of viral DNA is a noteworthy link; the entire process requires a powered motor that binds to viral DNA and carries it into the preformed capsid. Studies have shown that this power motor is a complex composed of a large subunit, a small subunit, and a third subunit, which are collectively known as terminase. The terminase large subunit is highly conserved in herpesvirus. It mainly includes two domains: the C-terminal nuclease domain, which cuts the viral concatemeric DNA into a monomeric genome, and the N-terminal ATPase domain, which hydrolyzes ATP to provide energy for the genome cutting and transfer activities. Because this process is not present in eukaryotic cells, it provides a reliable theoretical basis for the development of safe and effective anti-herpesvirus drugs. This article reviews the genetic characteristics, protein structure, and function of the herpesvirus terminase large subunit, as well as the antiviral drugs that target the terminase large subunit. We hope to provide a theoretical basis for the prevention and treatment of herpesvirus. [ABSTRACT FROM AUTHOR]

Saprolegnia ferax (S. ferax) is one of the most highly pathogenic oomycetes species in freshwater aquatic environments causing serious saprolegniosis. Linalool is a kind of natural alternative of antibiotics existing in various plants essential oils. In this study, the in vitro and in vivo anti-oomycetes activity and mode of action of linalool against S. ferax CQT1 were investigated. For in vitro test, linalool exhibited mycelium growth and zoospore production inhibition at 0.1% (v /v, 0.862 mg/ml) and 0.025% (v/v, 0.216 mg/ml), respectively. The mycelium was wrinkled, deformed, and shrunken after treatment with linalool. Linalool altered membrane permeability, caused permanent damage, or membrane breakdown. Further, the transcriptomic analysis showed that: (1) Linalool affected the oxidation and metabolism of fatty acids, leading to mitochondrial dysfunction and the inhibition of energy supply. (2) The increase in glycerophospholipid metabolism is probably the cell response to deal with cellular damage. (3) The degradation of branched chain amino acids may inhibit amino acid metabolism and result in the dysfunction of protein synthesis. (4) ABC transporters contribute to metabolic resistance to linalool and efflux of linalool outside of cells. For in vivo test, the cumulative survival rate of grass carp treated with linalool was significantly higher than those untreated with linalool, moreover, microscopic histopathology analysis results showed that there was robust mucus cell density in fish skin, the dermis and epidermis were relatively intact after linalool treatment. In all, our findings would provide foundations for the potential use of linalool to prevent and control S. ferax infection in the aquaculture industry. • Linalool, a kind of antibiotic alternative, has good potential to prevent and control S. ferax infection. • Linalool altered the membrane permeability, causing permanent damage, or membrane breakdown of mycelium. • Linalool treatment impacted energy metabolism, ABC transporters, and protein synthesis. • Linalool significantly improved the survival rate and relieved symptoms of grass carp infected with saprolegniosis. [ABSTRACT FROM AUTHOR]

Venetoclax (VEN)-based regimens are the standard of care for elderly or unfit patients with newly diagnosed (ND) acute myeloid leukemia (AML). Some single-arm studies have implied that hypomethylating agents (HMAs) plus priming regimens may potentially provide an alternative therapeutic approach, owing to encouraging efficacy seen. However, no comparative data exists yet regarding these two treatment approaches. In this retrospective multi-center cohort study, we enrolled 294 ND AML patients, allocating 167 to the HMA + priming group and 127 to the VEN-based group. Treatment response and overall survival (OS) were compared between groups. Molecular subgroup analyses were also conducted. With a median of two cycles for HMA + priming group, the overall response (ORR) was 65.3%, including 55.1% complete remission (CR), 9.6% CR with incomplete hematologic recovery (CRi) and 0.6% morphologic leukemia-free state (MLFS). With a median of two cycles for VEN-based group, the ORR was 70.9%, including 46.5% CR, 18.9% CRi, and 5.5% MLFS. Response differences (ORR or CR/CRi) between groups were not significant (p > 0.05). With a median follow-up of 10.1 months, median OSs were similar between groups (20.9 vs 16.3 months, p = 0.41). However, VEN regimens demonstrated superior CR/CRi for patients with mutations in FLT3, IDH1/2, and NPM1 compared to HMA + priming (80.0% vs 35.0%, p = 0.01; 90.9% vs 65.5%, p = 0.02; 90.9% and 65.5%, p = 0.02, respectively). In conclusion, HMAs plus modified priming regimens might be a potential alternative therapeutic approach for patients with ND AML, but VEN-based regimens presented predominance in specific molecular subgroups. Molecular characteristics contribute to guiding choice of treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: The swordtip squid (Uroteuthis edulis) is both of commercial and ecological importance and vital in the coastal China ecosystem. However, the limited ecological research requires further investigations into its habitat preferences. To address this, we studied how the habitat of U. edulis varies and what environmental factors drive its movements across different seasons in the East China Sea (ECS) and southern Yellow Sea. The study found that U. edulis predominantly inhabited the central and southern regions of the ECS, with a slight shift in the geometric center of its habitat across seasons. The preferences for sea surface temperature, sea surface height, and depth were the primary factors affecting its distribution. During summer and autumn, the suitable habitats of U. edulis were larger and expanded northwards towards the coastline, but in spring and winter, they retreated southwards to waters near the edge of the ECS continental shelf. These patterns are likely influenced by the changing mixture of ocean currents and varying environmental conditions throughout the year. This study provides valuable insight into how U. edulis is distributed in response to the changing environment, which can help to better manage and protect their populations. Accurately modeling the distribution of keystone species is of utmost importance to gain a comprehensive understanding of their complex ecological dynamics and to develop effective strategies for sustainable scientific management. In the coastal China ecosystem, the swordtip squid (Uroteuthis edulis) stands out as a keystone species with significant commercial and ecological value. Despite its importance, research on the ecological dynamics of this species remains limited and requires further investigation. To investigate the spatial and temporal variability in the distribution of U. edulis and identify the key environmental drivers in the East China Sea (ECS) and southern Yellow Sea across different seasons, we generated ensemble models using oceanographic variables and fishery-independent scientific survey data collected from 2016 to 2018. Our results revealed that U. edulis predominantly inhabited the central and southern regions of the ECS throughout the year. The primary environmental variables driving its distribution varied by season, with the sea surface temperature being the most important in spring, sea surface height in summer and autumn, and depth in winter. During summer and autumn, the suitable habitats of U. edulis were found to be largest and extended northwards towards the coastline. However, they migrated southwards to the waters near the edge of the ECS continental shelf with smaller suitable areas in the spring and winter. These results suggested that U. edulis exhibited season-specific habitat preferences and responded to changing environmental conditions throughout the year. The observed seasonal distribution patterns were likely influenced by the fluctuating mixture of waters (ocean currents) from different sources, with varying physical and chemical characteristics throughout the year. Our study provides baseline data for comprehending the population dynamics of U. edulis and highlights the significance of considering species' habitat preferences in a dynamic environment. [ABSTRACT FROM AUTHOR]

Suitable flow field designs significantly affect the performance of high temperature proton exchange membrane (HT-PEM) fuel cells. Previous designs both in terms of shape and size optimisation are still inadequate in the category of experiential design method, depend on the experience of designers and lack of explainable theories, leading to uncertainties in the design process. To address this issue, a novel flow field design method for innovative flow fields using combined topology and surrogate models is proposed, in which a topology model is built to optimise to obtain the basic shape of flow field, then a numerical model is established to train a surrogate model for the optimum design. Finally, a radial basis function (RBF) model is built to determine the optimum channel parameters. With this method, a 25 cm2 leaf-like flow field with a diagonal inlet outlet is designed and investigated which outperforms the initial serpentine design with a 7.95% increase in current density, a 8.47% increase in actual power, and a 97.8% reduction in pressure drop at 0.50 V. This novel flow field design method combines the advantages of the topology and surrogate models in shape and size optimisation, respectively. It significantly reduces the design threshold and can be widely used in innovative flow field design in energy and other engineering fields. • A nature-inspired leaf-like flow field is designed for HT-PEM fuel cells. • Topology and surrogate models are combined for shape and geometry optimisation. • Novel leaf-like flow field achieves improved performance over traditional serpentine design. • Current density and real power are improved by 7.95% and 8.47%, respectively, at 0.5 V. • Pressure drop is reduced by 97.8% in comparison with serpentine flow field. [ABSTRACT FROM AUTHOR]

Simple Summary: The red-crowned crane Grus japonensis in the National Yancheng Rare Birds Nature Reserve needs large quantities of high-protein food sources, including juvenile fishes, to fuel their migratory journeys. Some fish species use the tide to complete inshore migration, and they gradually migrate from the open sea to the surf area to find a more suitable habitat. In this paper, we used a fixed station to assess how the number of characteristics and developmental stages of fish larvae vary with the tide and how these values are related to environmental variables. We found that the number of species and larval individuals were highest and lowest, respectively, at the highest and lowest tidal height, and they obviously increased and decreased with the rising and ebb tide, respectively. We detected a tendency for Cynoglossus joyneri, Larimichthys polyactis, and Liza haematocheila to be present at higher density during the rising tide compared with the ebb tide, indicating that they were moving to the near shore from the open sea. Our findings indicate that the variation in numbers of the larvae and juveniles depends on species and developmental stage. These results provide a better understanding of the habitat of prey species of the wild bird population. The National Yancheng Rare Birds Nature Reserve is a vitally important staging habitat for the wild population of red-crowned cranes (Grus japonensis) in China. The population relies on local high-protein food sources, such as fish juveniles, to fuel their migratory journeys. However, little is known about the ecology of the fish larvae and juveniles that migrate to the inshore area via tidal rhythm in Subei Shoal, which is adjacent to the reserve. Therefore, we used a fixed study station (32°55′1.2″ N, 121°19′58.8″ E) to conduct a continuous 15-day ichthyoplankton survey at 2 h intervals beginning at 05:00 on 25 April and ending at 03:00 on 10 May 2019. We identified the tidal variations in the number of fish larvae and juveniles and the number at various developmental stages and assessed how they were related to environmental variables such as sea surface temperature, salinity, turbidity, and tidal height in the Dafeng Sea area of Subei Shoal. We found that the number of species and larval individuals were highest and lowest, respectively, at the highest and lowest tidal height, and they obviously increased and decreased with the rising and ebb tide, respectively. Our findings indicate that the variation in numbers of the larvae and juveniles depends on species and developmental stage. The species Acanthogobius ommaturus, Pholis fangi, Cynoglossus joyneri, Liza haematocheila, and Lateolabrax japonicus and the total number of larvae were most influenced by tidal height. These results provide a better understanding of the habitat of prey species of the red-crowned crane wild population as well as scientific data that can be applied to manage the wild population in the reserve sustainably. [ABSTRACT FROM AUTHOR]

We present here an iron‐catalyzed oxidative Csp3−Csp3 bond cleavage of unstrained tertiary alkyl aromatics to provide a range of synthetically useful arylketones even with H2O2 as the oxidant. This method is operationally simple, scalable, and eco‐friendly, as well as suitable for the late‐stage oxidation of complex molecules bearing hydroxy groups, making it a valuable tool in organic synthesis. [ABSTRACT FROM AUTHOR]

Plakophilin 1 (PKP1) is an important plaque component of desmosomes, major intercellular adhesive junctions that act as anchorage points for intermediate filaments. Abnormal expression of PKP1 was observed in various types of cancer, however so far its function in lung cancer has not yet been elucidated. The expression of PKP1 was analyzed by RT-PCR and western blotting in lung cancer cell lines. The protein expression of PKP1 was evaluated by immunohistochemistry in tissue microarray. The epigenetic mechanism of PKP1 was explored by demethylation test, bisulfite sequencing and Methylation-Specific-PCR. The function of PKP1 was investigated by stable transfection with an expression vector. We found that PKP1 was downregulated in 6 out of 8 lung cancer cell lines, and downregulation of PKP1 was associated with DNA hypermethylation. In advanced primary lung tumor samples, higher expression of PKP1 was significantly associated with favorable clinical outcome (p =.003). Ectopic expression of PKP1 inhibited cell proliferation, colony formation, migration/invasion and enhanced apoptosis. These phenomena are accompanied by increased caspase 3/7 activities and cleaved PARP-1 as well as decreased extracellular signal–regulated kinase (ERK) activity. Taken together, our data suggest that PKP1 is a novel tumor suppressor and its protein expression might be a potential prognostic marker for patients with advanced lung cancer. [ABSTRACT FROM AUTHOR]

Abstract Phenelzine was first employed to design new aryl hydrazine-based LSD1 inhibitors based on the experience-based discovery (EBD) strategy. Among these compounds, D8 potently inhibited LSD1 (IC 50 = 882.30 nM) in a reversible manner. Compound D8 was selective to LSD1 over MAO-A/B and showed H3K4me2 competitive binding to LSD1. The interaction between H3K4me2 and LSD1 was also confirmed by the Co-IP assay. In LSD1 overexpressed A549 cells, compound D8 dose-dependently induced accumulation of LSD1 substrates H3K4me1/2 and H3K9me1/2, showed cellular target engagement to LSD1 and significantly inhibited cell migration of A549 cells. Docking studies suggested that compound D8 occupied the peptide binding region and therefore blocked the access of the peptide substrate to the FAD, finally leading to the demethylase activity inhibition of LSD1. The findings indicate that aryl hydrazines are new scaffolds for the design of LSD1 inhibitors, the identification of D8 provides further evidence for our previously proposed general principle that fused heterocycles with an amine group are potentially active toward LSD1 by competitive binding to LSD1 with H3 peptide substrates. Graphical abstract Image 1 Highlights • Phenelzine was first employed to design new aryl hydrazine-based LSD1 inhibitors. • D8 reversibly inhibited LSD1 (IC 50 = 882.30 nM) and showed H3K4me2 competitive binding to LSD1. • In A549 cells, D8 induced accumulation of H3K4me1/2 and H3K9me1/2. • D8 was cellularly engaged to LSD1 and inhibited migration of A549 cells. • The aryl hydrazines are new scaffolds for the design of LSD1 inhibitors. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Nontoxic ABCB1 modulator WS-10 was identified from our in-house molecular library. • WS-10 selectively modulates ABCB1-mediated multidrug resistance. • WS-10 enhanced the intracellular accumulation of paclitaxel in SW620/Ad300 cells. • The CETSA assay showed that WS-10 could bind to ABCB1 protein. Abstract Multidrug resistance (MDR) has been shown to reduce the effectiveness of chemotherapy. Strategies to overcoming MDR have been widely explored in the last decades, leading to a generation of numerous small molecules targeting ABC and MRP transporters. Among the ABC family, ABCB1 plays key roles in the development of drug resistance and is the most well studied. In this work, we report the discovery of non-toxic [1,2,4]triazolo[1,5- a ]pyrimidin-7-one (WS-10) from our structurally diverse in-house compound collection that selectively modulates ABCB1-mediated multidrug resistance. WS-10 enhanced the intracellular accumulation of paclitaxel in SW620/Ad300 cells, but did not affect the expression of ABCB1 Protein and ABCB1 localization. The cellular thermal shift assay (CETSA) showed that WS-10 was able to bind to ABCB1, which could be responsible for the reversal effect of WS-10 toward paclitaxel and doxorubicin in SW620/Ad300 cells. Docking simulations were performed to show the possible binding modes of WS-10 within ABCB1 transporter. To conclude, WS-10 could be used as a template for designing new ABCB1 modulators to overcome ABCB1-mediated multidrug resistance. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights •The nontoxic ABCB1 modulator WS-10 was identified from our in-house molecular library. • WS-10 selectively modulated ABCB1-mediated multidrug resistance. • WS-10 enhanced the intracellular accumulation of Paclitaxel in SW620/Ad300 cells. • The CETSA assay showed that WS-10 could bind to ABCB1 protein. Abstract Multidrug resistance (MDR) has been shown to reduce the effectiveness of chemotherapy. Strategies to overcoming MDR have been widely explored in the last decades, leading to a generation of numerous small molecules targeting ABC and MRP transporters. Among the ABC family, ABCB1 plays key roles in the development of drug resistance and is the most well studied. In this work, we report the discovery of a non-toxic [1,2,4]triazolo[1,5- a ]pyrimidin-7-one (WS-10) from our structurally diverse in-house compound collection that selectively modulates ABCB1-mediated multidrug resistance. WS-10 enhanced the intracellular accumulation of paclitaxel in SW620/Ad300 cells, but did not affect the expression of ABCB1 Protein and ABCB1 localization. The cellular thermal shift assay (CETSA) showed that WS-10 was able to bind to ABCB1, which could be responsible for the reversal effect of WS-10 toward paclitaxel and doxorubicin in SW620/Ad300 cells. Docking simulations were performed to show the possible binding modes of WS-10 within ABCB1 transporter. To conclude, WS-10 could be used as a template for designing new ABCB1 modulators to overcome ABCB1-mediated multidrug resistance. [ABSTRACT FROM AUTHOR]

Keywords: palladium catalysis; carbonylation; aryl iodides; alkenylboronic acids; chalcones; enones EN palladium catalysis carbonylation aryl iodides alkenylboronic acids chalcones enones 1280 1284 5 06/19/23 20230704 NES 230704 , -Unsaturated ketones are prevalent structural motifs in natural products that display a wide spectrum of biological activities. In summary, we have developed an operationally simple, efficient, and ligand-free palladium-catalyzed carbonylation of aryl iodides with alkenylboronic acids for the selective synthesis of bioactive chalcones and -branched enones. Palladium catalysis, aryl iodides, carbonylation, chalcones, enones, alkenylboronic acids. [Extracted from the article]

The distribution of the early life stages of Larimichthys polyactis indicates the availability of suitable spawning and nursing grounds and enables a better understanding of the distribution of its geographic subpopulations and isolation. Large‐scale quantitative ichthyoplankton surveys of L. polyactis were performed from March to July 2018, and a numerical hydrodynamic model was applied to explore the spatiotemporal distribution and habitats of L. polyactis early life stages adjacent to the Changjiang River Estuary. Two distinct early life stage distribution patterns were found. One occurred during March and April in the deep waters seaward of the Changjiang River bottom plume front, to the east and southeast of the Changjiang River Estuary. The other occurred in May and June throughout the entire water column in coastal waters to the east and north of the Changjiang River Estuary. Rising seasonal temperatures, and the local dynamic processes such as the Changjiang River plume, determined the transitions between the two distribution patterns. A potential fish larval migration route from the southern deep shelf waters to the northern coastal waters within the motor‐trawl prohibition line was suggested. This study contributes to our understanding of the mixture of habitats used by the two L. polyactis subpopulations in the southern Yellow Sea and the East China Sea. [ABSTRACT FROM AUTHOR]

Farnesyl (Far) and palmitoyl (Pal) anchors play important roles in the traffic of many lipidated proteins. Herein, we show the distinctive interactions and influences of the two lipid modifications on lipid rafts (LRs) and non-raft-like membranes using molecular dynamics simulations. Palmitoyl anchors behave in a more ordered fashion, pack tighter with the lipids of LRs and diffuse at a slower rate than farnesyl anchors in LRs. When interacting with non-raft-like membranes these two types of anchors become less ordered, pack more loosely with lipids, and diffuse at a higher rate. By calculating both the number of contacts per chain and the number of contact atoms per carbon of the two anchors with the lipid components, we found that the palmitoyl chains preferred to associate with the saturated chains of lipids and cholesterol molecules in LRs, while farnesyl chains favored association with saturated chains and unsaturated chains. For non-raft-like membranes, these two lipid anchors had roughly the same preference for the three types of contact lipid chains. Additionally, palmitoyl anchors caused cholesterol to orient more perpendicular to the membrane surface, surrounding lipids to become more ordered, and lipid lateral fluidity to reduce significantly, compared to farnesyl anchors in LRs. By contrast, the POPE and DSPC became much less ordered, cholesterol became more tilted, and lipids became more fluid, when the two types lipid anchors were inserted in non-raft-like membranes. These findings are useful for understanding the traffic mechanisms of lipidated proteins with farnesyl and palmitoyl modifications in cell membranes. [ABSTRACT FROM AUTHOR]

Human action recognition is an important yet challenging task. This paper presents a low-cost descriptor called 3D histograms of texture (3DHoTs) to extract discriminant features from a sequence of depth maps. 3DHoTs are derived from projecting depth frames onto three orthogonal Cartesian planes, i.e., the frontal, side, and top planes, and thus compactly characterize the salient information of a specific action, on which texture features are calculated to represent the action. Besides this fast feature descriptor, a new multi-class boosting classifier (MBC) is also proposed to efficiently exploit different kinds of features in a unified framework for action classification. Compared with the existing boosting frameworks, we add a new multi-class constraint into the objective function, which helps to maintain a better margin distribution by maximizing the mean of margin, whereas still minimizing the variance of margin. Experiments on the MSRAction3D, MSRGesture3D, MSRActivity3D, and UTD-MHAD data sets demonstrate that the proposed system combining 3DHoTs and MBC is superior to the state of the art. [ABSTRACT FROM PUBLISHER]

The nanocrystals of title are prepared at different pH values by hydrothermal reaction of Na2WO4 and either MnCl2, MnCO3, or Mn(OH)2 as Mn source (autoclave, 150 °C, 3 h). [ABSTRACT FROM AUTHOR]

Background. The poor prognosis of the highly malignant tumor osteosarcoma stems from its drug resistance and therefore exploring its resistance mechanisms will help us identify more effective treatment options. However, the effects of miR-125b-5p on drug resistance in osteosarcoma cells are still unclear. Methods. To study the effects of miR-125b-5p on drug resistance in osteosarcoma cells. Osteosarcoma-resistant miR-125b-5p was obtained from the databases GeneCards and g:Profiler. CCK8, western blot, and transwell were applied for the detection of the miR-125b-5p effects on proliferation, migration, invasion, apoptosis, and drug resistance in osteosarcoma. Bioinformatics is aimed at demonstrating the targeting factor miR-125b-5p, performing protein interaction enrichment analysis by Metascape, and finally validating by binding sites. Results. Upregulation of miR-125b-5p restrains proliferation, migration, and invasion of osteosarcoma and promotes apoptosis. In addition, miR-125b-5p can restore drug sensitivity in drug-resistant osteosarcoma. miR-125-5p restrains the signal transducer and inhibits the transcription 3 (STAT3) expression activator via targeting its 3 ′ -UTR. STAT3 affects drug-resistant osteosarcoma to regulate the ABC transporter. Conclusion. miR-125b-5p/STAT3 axis mediates the drug resistance of osteosarcoma by acting on ABC transporter. [ABSTRACT FROM AUTHOR]

Polydopamine fluorescent organic nanomaterials present unique physicochemical and biological properties, which have great potential application in bio-imaging and chemical sensors. Here, folic acid (FA) adjustive polydopamine (PDA) fluorescent organic nanoparticles (FA-PDA FONs) were prepared by a facile one-pot self-polymerization strategy using dopamine (DA) and FA as precursors under mild conditions. The as-prepared FA-PDA FONs had an average size of 1.9 ± 0.3 nm in diameter with great aqueous dispersibility, and the FA-PDA FONs solution exhibit intense blue fluorescence under 365 nm UV lamp, and the quantum yield is ~8.27%. The FA-PDA FONs could be stable in a relatively wide pH range and high ionic strength salt solution, and the fluorescence intensities are constant. More importantly, here we developed a method for rapidly selective and sensitive detection of mercury ions (Hg2+) within 10 s using FA-PDA FONs based probe, the fluorescence intensities of FA-PDA FONs presented a great linear relationship to Hg2+ concentration, the linear range and limit of detection (LOD) were 0–18 µM and 0.18 µM, respectively. Furthermore, the feasibility of the developed Hg2+ sensor was verified by determination of Hg2+ in mineral water and tap water samples with satisfactory results. [ABSTRACT FROM AUTHOR]

PbWO4 dendrites are prepared by irradiation of an aqueous solution of K2C2O4, Na2WO4, and Pb(NO3)2 with a high-intensity ultrasonic horn under ambient air. [ABSTRACT FROM AUTHOR]

A correction to the article "Mechanistic Studies of the Spore Photoproduct Lyase via a Single Cysteine Mutation" that was published in the November 27, 2012 issue is presented.

Abstract: In this paper, we report a simple hydrothermal method to synthesize barium strontium titanate (Ba1−x Sr x TiO3, x =0–1) dendrites without any templates. The obtained products were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), electron diffraction (ED), and energy-dispersive X-ray spectroscopy (EDX), respectively. All the samples were identified as cubic perovskite phase by XRD and the obtained Ba1−x Sr x TiO3 (x =0–1) dendrites were single-crystal. The formation process of Ba1−x Sr x TiO3 dendritic structures was also investigated. It is rational to expect that dendritic structures of other perovskite oxides may also be synthesized by this simple method. [Copyright &y& Elsevier]

Bacterial fruit blotch (BFB) is a disease of cucurbit plants caused by Acidovorax citrulli. Although A. citrulli has great destructive potential, the molecular mechanisms of pathogenicity of A. citrulli are not clear, particularly with regard to its type III secreted effectors. In this study, we characterized the type III secreted effector protein, AopV, from A. citrulli strain Aac5. We show that AopV significantly inhibits reactive oxygen species and the expression of PTI marker genes, and helps the growth of Pseudomonas syringae D36E in Nicotiana benthamiana. In addition, we found that the aromatic dehydratase ADT6 from watermelon was a target of AopV. AopV interacts with ADT6 in vivo and in vitro. Subcellular localization indicated ADT6 and AopV were co-located at the cell membrane. Together, our results reveal that AopV suppresses plant immunity and targets ADT6 in the cell membrane. These findings provide an new characterization of the molecular interaction of A. citrulli effector protein AopV with host cells. [ABSTRACT FROM AUTHOR]

Bacterial fruit blotch (BFB) caused by Acidovorax citrulli (Ac) is a devastating watermelon disease that severely impacts the global watermelon industry. Like other Gram-negative bacteria, the type three secretion system (T3SS) is the main pathogenicity factor of A. citrulli. The T3SS apparatus gene hrpE codes for the Hrp pilus and serves as a conduit to secret effector proteins into host cells. In this study, we found that the deletion of hrpE in A. citrulli results in the loss of pathogenicity on hosts and the hypersensitive response on non-hosts. In addition, the A. citrulli hrpE mutant showed a reduction in in vitro growth, in planta colonization, swimming and twitching motility, and displayed increases in biofilm formation ability compared to the wild type. However, when HrpE was transiently expressed in hosts, the defense responses, including reactive oxygen species bursts, callose deposition, and expression of defense-related genes, were activated. Thus, the A. Citrulli growth in HrpE-pretreated hosts was suppressed. These results indicated that HrpE is essential for A. citrulli virulence but can also be used by hosts to help resist A. citrulli. Our findings provide a better understanding of the T3SS pathogenesis in A. citrulli, thus providing a molecular basis for biopesticide development, and facilitating the effective control of BFB. [ABSTRACT FROM AUTHOR]

The reduction of fishmeal in aquafeeds has been the concern of researchers. Replacing fishmeal with plant proteins affects intestinal function and inflammation, but the interaction between the intestinal responses and gut microbiota remains unclear. In this study, juvenile channel catfish (Ictalurus punctatus) was fed with four diets in which enzymatic rice protein (RP) replaced fishmeal at levels of 0 (FM), 2.5% (RP2.5), 5.0% (RP5.0), and 7.5% (RP7.5) for 8 weeks to solve the problem mentioned above. Quantification of intestinal morphology showed that 2.5% or 5.0% RP significantly increased villus length and goblet cell number, accompanied by higher activities of intestinal trypsin, alkaline phosphatase (AKP), and Na+/K+-ATPase (NKA) in RP2.5 group (P < 0.05). In contrast, 7.5% RP slightly damaged the intestinal mucosa and significantly reduced the activities of amylase, AKP, and NKA, as well as decreased serum complement 4 (C4) and immunoglobulin M (IgM). Noteworthy, RT-qPCR showed that 2.5% RP significantly down-regulated intestinal mRNA expression level of il8 , while up-regulated mif , tlr4 , tlr7 , tgfβ3 , and cldn2. In contrast, 7.5% RP up-regulated the mRNA expression levels of il1β , il8 , and mif , while down-regulated cldn3d. Analysis of gut microbiota showed that 2.5% RP increased the relative abundance of Bacteroidetes and significantly activated potential functions of gut microbiota involved in carbohydrate metabolism. The 7.5% RP increased the diversity of the gut microbiota, accompanied by a significant increase in the relative abundance of conditionally pathogenic bacteria such as Vibrio , Serratia , and Aeromonas (classified as Proteobacteria). Notably, Vibrio was the biomarker species with the greatest difference between the FM and RP7.5 groups (genus level). Correlation analysis indicated that Vibrio may affect immunity through the C4 pathway and further lead to gut inflammation and digestive impairment. Taken above, these results indicated that RP could affect intestinal morphology, digestion, and inflammation, and interact with the composition and potential function of gut microbiota. The low RP supplement (2.5%) improved intestinal morphology and digestion, while high supplement (7.5%) disrupted gut microbiota homeostasis, resulting in damage to intestinal mucosa and inflammatory response. • Replacing 2.5% of fishmeal with RP improved gut morphology and digestion. • The 7.5% RP supplement resulted in damaged intestinal mucosa, decreased digestion, and inflammatory responses. • The 7.5% RP induced gut inflammation by affecting the abundance and predicted function ofpathogenic bacteria. [ABSTRACT FROM AUTHOR]

Summary The Diels-Alder [4 + 2] cycloaddition reaction is one of the most powerful and elegant organic synthesis methods for forming 6-membered molecules and has been known for nearly a century. However, whether and how enzymes catalyze this type of reaction is still not completely clear. Here we focus on PyrI4, an enzyme found in the biosynthetic pathway of pyrroindomycins where it catalyzes the formation of a spiro-conjugate via an enzyme-dependent exo -selective [4 + 2] cycloaddition reaction. We report the crystal structures of PyrI4 alone and in complex with its product. Comparative analysis of these structures, combined with biochemical analysis, lead us to propose a unique trapping mechanism whereby the lid-like action of the N-terminal tail imposes conformational constraints on the β barrel catalytic core, which enhances the proximity and polarization effects of reactive groups (1,3-diene and alkene) to drive cyclization in a regio- and stereo-specific manner. This work represents an important step toward the wider application of enzyme-catalyzed [4 + 2] cyclization for synthetic purposes. [ABSTRACT FROM AUTHOR]

Icaritin (ICT) is a traditional Chinese medicinal herb proved to be neuroprotective and exerts promoting effects on cardiac differentiation. However, its role in cardioprotection against myocardial ischemia/reperfusion (MI/R) injury remains largely unknown. This study aimed to investigate the effects of ICT treatment on MI/R injury and the underlying mechanisms. Rats were subjected to 30 min of myocardial ischemic insult followed by 3 h of reperfusion. ICT (3, 10, and 30 mg/kg) was administered intraperitoneally 10 min before reperfusion. ICT treatment at the dose of 10 and 30 mg/kg improved cardiac function and limited infarct size following MI/R. Meanwhile, ICT reduced plasma creatine kinase (CK), lactate dehydrogenase (LDH) activities and cardiomyocyte apoptosis in I/R heart tissue. Moreover, ICT treatment not only inhibited the pro-inflammatory cytokine TNF-α production and increased the anti-inflammatory cytokine IL-10 level in myocardium but also reduced the increase in the generation of superoxide content and malondialdehyde (MDA) formation and simultaneously increased the anti-oxidant capability in I/R hearts. Furthermore, ICT treatment increased Akt phosphorylation and inhibited PTEN expression in I/R hearts. PI3K inhibitor wortmannin inhibited ICT-enhanced Akt phosphorylation, and blunted ICT-mediated anti-oxidative and anti-inflammatory effects and cardioprotection. Our study indicated for the first time that ICT reduces inflammation and oxidative stress and protects against MI/R injury in rats, which might be via a PI3K-Akt-dependent mechanism. [ABSTRACT FROM AUTHOR]

A novel electrochemical sensor based on Cu-MOF-199 [Cu-MOF-199 = Cu 3 (BTC) 2 (BTC = 1,3,5-benzenetricarboxylicacid)] and SWCNTs (single-walled carbon nanotubes) was fabricated for the simultaneous determination of hydroquinone (HQ) and catechol (CT). The modification procedure was carried out through casting SWCNTs on the bare glassy carbon electrode (GCE) and followed by the electrodeposition of Cu-MOF-199 on the SWCNTs modified electrode. Cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM) were performed to characterize the electrochemical performance and surface characteristics of the as-prepared sensor. The composite electrode exhibited an excellent electrocatalytic activity with increased electrochemical signals towards the oxidation of HQ and CT, owing to the synergistic effect of SWCNTs and Cu-MOF-199. Under the optimized condition, the linear response range were from 0.1 to 1453 μmol L −1 ( R HQ = 0.9999) for HQ and 0.1–1150 μmol L −1 ( R CT = 0.9990) for CT. The detection limits for HQ and CT were as low as 0.08 and 0.1 μmol L −1 , respectively. Moreover, the modified electrode presented the good reproducibility and the excellent anti-interference performance. The analytical performance of the developed sensor for the simultaneous detection of HQ and CT had been evaluated in practical samples with satisfying results. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel NIR fluorescent probe for detection of NO with large Stokes shift was developed. • Probe could target in Golgi and monitor NO fluctuation upon stimulation with Glu and LPS. • Probe could in vivo imaging NO concentration in brain of depression-like mice model via tail vein injection. Depression is a debilitating mental illness that poses a serious threat to human health. Nitric Oxide (NO), as an important gasotransmitter, is closely associated with the pathogenesis of depressive disorders. Effective monitoring of NO fluctuation is beneficial for the diagnosis of depression and therapy assessment of antidepressants. Currently, there is a lack of effective methods for rapidly and sensitively identifying NO and elucidating its relationship with depression diseases. Herein, we developed a NIR dye TJ730-based fluorescent probe TJ730-Golgi-NO incorporating benzenesulfonamide as a Golgi-targeted moiety and the thiosemicarbazide group for NO detection. The probe exhibited turn-on fluorescence ability and a large Stokes shift of 158 nm, which shows high sensitivity, selectivity, and rapid response (<1 min) for NO detection. TJ730-Golgi-NO could detect exogenous and endogenous NO in cells stimulated by Glu and LPS, and target Golgi apparatus. Moreover, we disclose a significant increase of NO in the depression model and a weak fluorescence evidenced in the fluoxetine-treated depression mice. This study provides a competent tool for studying the function of NO and helping improve the effective treatment of depression diseases. [ABSTRACT FROM AUTHOR]

Oncogenic RAS and RAF signaling has been implicated in contributing to radioresistance in pancreatic and thyroid cancers. In this study, we sought to better clarify molecular mechanisms contributing to this effect. We discovered that miRNA 296–3p (miR-296–3p) is significantly correlated with radiosensitivity in a panel of pancreatic cancer cells, and miR-296–3p is highly expressed in normal cells, but low in cancer cell lines. Elevated expression of miR-296–3p increases radiosensitization while decreasing the expression of the DNA repair enzyme RAD18 in both pancreatic and thyroid cancer cells. RAD18 is overexpressed in both pancreatic and thyroid tumors compared to matched normal controls, and high expression of RAD18 in tumors is associated with poor prognostic features. Modulating the expression of mutant KRAS in pancreatic cancer cells or mutant BRAF in thyroid cancer cells demonstrates a tight regulation of RAD18 expression in both cancer types. Depletion of RAD18 results in DNA damage and radiation-induced cell death. Importantly, RAD18 depletion in combination with radiotherapy results in marked and sustained tumor regression in KRAS mutant pancreatic cancer orthotopic tumors and BRAF mutant thyroid heterotopic tumors. Overall, our findings identify a novel coordinated RAS/RAF-miR-296-3p-RAD18 signaling network in pancreatic and thyroid cancer cells, which leads to enhanced radioresistance. • Oncogenic RAS and RAF signaling play a significant role in radioresistance in pancreatic and thyroid cancers. • miR-296–3p is associated with radiosensitivity and is highly expressed in normal cells but low in cancer cell lines. • miR-296–3p suppresses RAD18 expression in both cancer types, and RAD18 overexpression is associated with poor prognosis. • RAD18 depletion with radiotherapy induces significant tumor regression in KRAS pancreatic & BRAF thyroid cancers. • These findings shed light on a novel mechanism contributing to enhanced radioresistance in pancreatic and thyroid cancers. [ABSTRACT FROM AUTHOR]

A water-soluble fingerprint probe, GK-Ac, was designed and synthesized by using an unsymmetric structure of fluorescent groups. In the present contribution, incorporating a "rotor" structure to impede the rotation of rotational site groups, which can effectively enhance aggregation-induced emission and provide additional sites for modification. The results indicate that the fingerprint probe GK-Ac had faint fluorescence characteristics in aqueous solution, and the level 2 structure of latent fingerprints can be clearly observed at 450 nm fluorescence when soaked in lipid or sprayed with the GK-Ac aqueous solution. Moreover, the probe was also successfully applied to detect the level 3 structure of latent fingerprints with flat surfaces. The results can provide reliable theoretical guidance for the development of fingerprint fluorescence developer. [Display omitted] • An AIE-based water-soluble probe was designed and synthesized by using an unsymmetric structure. • The level 3 features of LFPs can be revealed by soaking or spraying with the GK-Ac. • GK-Ac only binds to lipids on LFPs and does not bind to other substances. [ABSTRACT FROM AUTHOR]