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Background: Anxiety and depression can influence adherence to Pre-exposure Prophylaxis (PrEP). However, there is limited research on the temporal dynamics of anxiety and depression among men who have sex with men (MSM) using PrEP. Methods: From December 2018 to November 2020, we administered the Hospital Anxiety and Depression Scale (HADS) to participants in the China Real-World Oral Intake of PrEP (CROPrEP) to measure their anxiety and depression levels. The group-based trajectory model (GBTM) depicted the dynamic changes of anxiety and depression scores over time. Results: A total of 1023 MSM were included, with 4523 follow-up assessments. The GBTM categorized the trajectories into three distinct patterns: consistently low (54.8% for anxiety, 60.7% for depression), consistently moderate (39.3% for anxiety, 31.4% for depression), and high but bell-shaped (5.9% for anxiety, 7.9% for depression). Higher anxiety levels were associated with being aged 18–30 years old, earning less than US$619 per month, female-identifying, adopting the bottom sexual role with men, and having two or more anal sex partners in the past three months; similarly, higher depression levels correlated with a monthly income under US$619, female-identifying, sexual behavior as bottom and a positive syphilis at baseline. PrEP adherence was notably lower in the high but bell-shaped anxiety and depression group compared to the other groups, particularly at the 12th-month follow-up. Conclusions: Close monitoring of anxiety and depression levels in MSM on PrEP is crucial. Provision of targeted mental health support is essential to enhance PrEP effectiveness. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) cause more than 100,000 deaths each year, which need efficient and non-resistant antibacterial agents. SAR analysis of 162 flavonoids from the plant in this paper suggested that lipophilic group at C-3 was crucial, and then 63 novel flavonoid derivatives were designed and total synthesized. Among them, the most promising K15 displayed potent bactericidal activity against clinically isolated MRSA and VRE (MICs = 0.25–1.00 μg/mL) with low toxicity and high membrane selectivity. Moreover, mechanism insights revealed that K15 avoided resistance by disrupting biofilm and targeting the membrane, while vancomycin caused 256 times resistance against MRSA, and ampicillin caused 16 times resistance against VRE by the same 20 generations inducing. K15 eliminated residual bacteria in mice skin MRSA-infected model (>99 %) and abdominal VRE-infected model (>92 %), which was superior to vancomycin and ampicillin. [Display omitted] • Guided synthesis of flavonoid derivatives from 162 natural flavonoids. • Amphiphilic flavonoid derivatives displayed broad-spectrum antibacterial activity. • K15 avoided resistance by damaging biofilm and targeting cell membranes. • K15 exhibited excellent therapeutic effect in vivo , superior to vancomycin and ampicillin. [ABSTRACT FROM AUTHOR]

[Display omitted] • Morusin killed MRSA quickly by the dual mechanism with H 2 S inhibition and membrane damage. • Morusin broken the homeostasis of MRSA between H 2 S and ROS by inhibiting the production of H 2 S and accumulating ROS. • Morusin could be developed as an antibacterial agent to overcome MDR-MRSA without drug resistance. It's urgent to discover new antibiotics along with the increasing emergence and dissemination of multidrug resistant (MDR) bacterial pathogens. In the present investigation, morusin exhibited rapid bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) by targeting the phospholipid of bacterial inner membrane, increasing membrane rigidity and disrupting bacterial homeostasis together with the membrane permeability, which caused fundamental metabolic disorders. Furthermore, morusin can also accumulate ROS, suppress H 2 S production, and aggravate oxidative damage in bacteria. Importantly, morusin also inhibited the spread of wounds and reduced the bacterial burden in the mouse model of skin infection caused by MRSA. It's a chance to meet the challenge of existing antibiotic resistance and avoid the development of bacterial resistance, given the multiple targets of morusin. [ABSTRACT FROM AUTHOR]

Abstract The prior β grain structure is recognized to be an important factor governing the mechanical properties of laser additive manufacturing (LAM) titanium alloys (ti-alloys) components. Five kinds of ti-alloys plates were fabricated by LAM process aiming to investigate the solidification behavior and grain morphology. Full columnar grains, full equiaxed grains and a special mixed grains structure were observed in LAM TC4, TB6 and TC11 plates, respectively, indicating that the formation tendency and volume fraction of equiaxed grains in LAM ti-alloys plates increase gradually with the increasing alloying content. It was proposed the formation of equiaxed grains is a multifactor functioning result of the constitutional supercooling and the remaining powders in the local melting pool. Graphical abstract Image 1 Highlights • Grain morphologies of five LAM ti-alloys are examined. • LAM TC4 and TB6 present full columnar and equiaxed grains respectively. • With the increasing Q of ti-alloys, the fraction of columnar grains decreases. • The equiaxed grains is a combined result of CS and remaining powders. [ABSTRACT FROM AUTHOR]

We present a weak blind signature scheme based on a genuinely entangled six qubits state. Different from classical blind signature schemes and current quantum signature schemes, our quantum weak blind signature scheme could guarantee not only the unconditionally security but also the anonymity of the message owner. To achieve that, quantum key distribution and one-time pad are adopted in our scheme. Our scheme has the characteristics of classical security and quantum security. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by social communication disability and stereotypic behavior. This study aims to investigate the impact of prenatal exposure to 1‐nitropyrene (1‐NP), a key component of motor vehicle exhaust, on autism‐like behaviors in a mouse model. Three‐chamber test finds that prenatal 1‐NP exposure causes autism‐like behaviors during the weaning period. Patch clamp shows that inhibitory synaptic transmission is reduced in medial prefrontal cortex of 1‐NP‐exposed weaning pups. Immunofluorescence finds that prenatal 1‐NP exposure reduces the number of prefrontal glutamate decarboxylase 67 (GAD67) positive interneurons in fetuses and weaning pups. Moreover, prenatal 1‐NP exposure retards tangential migration of GAD67‐positive interneurons and downregulates interneuron migration‐related genes, such as Nrg1, Erbb4, and Sema3F, in fetal forebrain. Mechanistically, prenatal 1‐NP exposure reduces hydroxymethylation of interneuron migration‐related genes through inhibiting ten‐eleven translocation (TET) activity in fetal forebrain. Supplement with alpha‐ketoglutarate (α‐KG), a cofactor of TET enzyme, reverses 1‐NP‐induced hypohydroxymethylation at specific sites of interneuron migration‐related genes. Moreover, α‐KG supplement alleviates 1‐NP‐induced migration retardation of interneurons in fetal forebrain. Finally, maternal α‐KG supplement improves 1‐NP‐induced autism‐like behaviors in weaning offspring. In conclusion, prenatal 1‐NP exposure causes autism‐like behavior partially by altering DNA hydroxymethylation of interneuron migration‐related genes in developing brain. [ABSTRACT FROM AUTHOR]

Neothalfine is a natural bisbenzylisoquinoline alkaloid with the abundant resource in medicinal plants and has not been reported its anti-tumor efficacy. In the present study, the anti-tumor efficacy was investigated and it showed broad-spectrum activity against several cancer cell lines, especially metastatic colorectal cancer (HCT116, SW620, T84) with the IC 50 values of 7.2, 5.9, 8.2 nM, respectively, roughly equal to well-known anti-tumor agent docetaxel (4.0, 4.7, 2.7 nM) and nearly 1000 folds than CPT-11 (4.4, 5.1, 6.9 μM). Furthermore, neothalfine inhibited colorectal cell proliferation by resulting in cell cycle arrest at the G2/M phase and induced apoptosis through the dysfunction of mitochondria to trigger intrinsic apoptotic pathway by untargeted metabolomic method, mitochondrial membrane potential, and caspase-3/7 activity assay. Moreover, neothalfine damaged colorectal cancer clonal spheres expansion significantly at the concentration of 3.5 nM with nearly 1000 folds efficacy than CPT-11 (3.0 µM). The results supported that neothalfine might be an anti-tumor lead for further investigation. [ABSTRACT FROM AUTHOR]

Ultrathin high-k dielectric ErAlO films were deposited on Si (100) substrates by using radio-frequency magnetron sputtering. The very flat surface of the annealed film with a rms roughness less than 0.25nm was observed by using an atomic force microscope. The film shows good thermal stability when annealing at 900°C for 30 s in the O2 ambient. The effective dielectric constant of the film is around 15.2, and a low leakage current of 8.4×10-5 A/cm2 at an electric field of 1MV/cm was achieved for the film with the equivalent oxide thickness of 2.0nm after annealing [ABSTRACT FROM AUTHOR]

As a traditional folk medicine, Acorus tatarinowii Schott was used to treat digestive diseases, such as diarrhea, which may be related to Candida albicans infection; however according to literature surveys, there have been few studies of A. tatarinowii focusing on its antimicrobial activity, and almost all describe investigations using crude extracts or fractions. The aims of the current study were to isolate and identify antifungal fractions of A. tatarinowii based on their antifungal activity, explore the preliminary mechanism of 60% ethanol elution (AT60) by metabonomics, and evaluate the antifungal activity of AT60 in vivo and in vitro , to provide natural resources against fungal infections. As a pilot evaluation of activity, A. tatarinowii fractions and compounds with antifungal bioactivity were isolated by bioactive-guided column chromatography, and identified by LC-QTOF-MS/MS and NMR spectroscopy. The antifungal effects of the active ingredients against resistant C. albicans were evaluated by in vivo and in vitro colony forming unit assays. The mechanism underlying the activity of AT60 against C. albicans was explored using an LC-QTOF-based metabonomics approach and fluorescence microscopy imaging. AT60 showed better activity against C. albicans than the same dose of the first line antifungal drugs, fluconazole and itraconazole (positive control drugs). Subsequent phytochemical investigation of AT60 identified twenty-five known compounds, six of which were isolated: asaraldehyde (7), 1-(2,4,5-trimethoxyphenyl)-1,2-propanediol (12), α-asarone (14), β-asarone (15), γ-asarone (18), acotatarone C (19). Further, the compounds α-asarone (14) and acotatarone C (19) may be responsible for the antifungal activity, and exhibit synergistic effects. Metabonomics analysis indicated that AT60 can inhibit biofilm formation by regulating the C. albicans protein kinase C pathway. Our results show that A. tatarinowii has potent bioactivity against C. albicans in vitro and in vivo, and can be considered an antifungal botanic agent. Image 1 [ABSTRACT FROM AUTHOR]

Sirtuin 6 (SIRT6) is an NAD+-dependent deacetylase with a significant role in 20% of all cancers, such as colon cancers and rectal adenocarcinoma. However, there is currently no effective drug for cancers related to SIRT6. To explore potential inhibitors of SIRT6, it is essential to reveal details of the interaction mechanisms between inhibitors and SIRT6 at the atomic level. The nature of small molecules from herbs have many advantages as inhibitors. Based on the conformational characteristics of the inhibitor Compound 9 (Asinex ID: BAS13555470), we explored the natural molecule Scutellarin, one compound of Huang Qin, which is an effective herb for curing cancer that has been described in the Traditional Chinese Medicine (TCMS) library. We investigated the interactions between SIRT6 and the inhibitors using molecular dynamics (MD) simulations. We illustrated that the structurally similar inhibitors have a similar binding mode to SIRT6 with residues—Leu9, Phe64, Val115, His133 and Trp188. Hydrophobic and π-stacking interactions play important roles in the interactions between SIRT6 and inhibitors. In summary, our results reveal the interactive mechanism of SIRT6 and the inhibitors and we also provide Scutellarin as a new potential inhibitor of SIRT6. Our study provides a new potential way to explore potential inhibitors from TCMS. [ABSTRACT FROM AUTHOR]

Monoterpene indole alkaloids exhibit structural diversity in herbal resources and have been developed as promising drugs owing to their significant biological activities. Confidential identification and quantification of monoterpene indole alkaloids is the key to quality control of target plants in industrial production but has rarely been reported. In this study, quantitative performance of three data acquisition modes of ultra‐high‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry including full scan, auto‐MS2 and target‐MS2, was evaluated and compared for specificity, sensitivity, linearity, precision, accuracy, and matrix effect using five monoterpene indole alkaloids (scholaricine, 19‐epi‐scholaricine, vallesamine, picrinine, and picralinal). Method validations indicated that target‐MS2 mode showed predominant performance for simultaneous annotation and quantification of analytes, and was then applied to determine monoterpene indole alkaloids in Alstonia scholaris (leaves, barks) after extraction procedures optimization using Box‐Behnken design of response surface methodology. The variations of A. scholaris monoterpene indole alkaloids in different plant parts, harvest periods, and post‐handling processes, were subsequently investigated. The results indicated that target‐MS2 mode could improve the quantitative capability of ultra‐high‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry for structure‐complex monoterpene indole alkaloids in herbal matrices. Alstonia scholaris, monoterpene indole alkaloids, quadrupole time of flight mass spectrometry, qualitative and quantitative analysis, ultra‐high‐performance liquid chromatography [ABSTRACT FROM AUTHOR]

Multi-elemental and multi-dimensional data are more and more important in the development of data-driven research, as is the case in modern paleontology, in which, in an examination by experts, or some day artificial intelligence, every fossil specimen plays a fundamental role. We here release a dataset of 1550 graptolite specimens representing 113 Ordovician to Silurian graptolite species or subspecies that are significant in global stratigraphic correlation and shale gas exploration. The dataset contains 2951 high-resolution images and a data table of each specimen's scientific information, including the taxonomic, geologic, and geographic information, comments, and references. Our dataset provides images for specialists or laypeople worldwide, is supported by the tool FSIDvis (Fossil Specimen Image Dataset Visualizer), which we developed to facilitate the interactive exploration of the rich-attribution image dataset, and includes a nonlinear-dimension reduction technique, t-SNE (t -distributed stochastic neighbor embedding), to project image data into a two-dimensional space to visualize and explore the similarities. Our dataset potentially contributes to virtual examinations of specimens, global bio-stratigraphic correlation, and improvement of the shale gas exploration efficiency. All data, images and the spreadsheet are available at 10.5281/zenodo.6688670 (Xu, 2022). [ABSTRACT FROM AUTHOR]

Two unique windmill-like aziridine-containing indole alkaloids, possessing an unprecedented 6/5/5/6/6/5/3 rigid ring system and an unusual azabicyclo[3.1.0]hexane core, were isolated from Alstonia scholaris. Their structures were established by spectroscopy, X-ray diffraction, and electronic circular dichroism calculations. The novel compounds exhibited significant anti-inflammatory bioactivity in vitro and alleviated LPS-induced acute lung injury in mice. [ABSTRACT FROM AUTHOR]

Depression is a common mental disorder with an increasing incidence. Several studies have demonstrated that cortical DNA hypomethylation is associated with depression-like behaviors. This study aims to investigate whether maternal vitamin D deficiency (VDD) induces depression-like behaviors and to explore the effects of folic acid supplement on VDD-induced cortical DNA hypomethylation in adult offspring. Female mice were fed with a VDD diet, beginning at 5 weeks of age and throughout pregnancy. Depression-like behaviors were evaluated, and cortical 5-methylcytosine (5mC) content was detected in adult offspring. Results showed that depression-like behaviors were observed in adult offspring of the VDD group. Cortical Ache and Oxtr mRNAs were upregulated in female offspring of the VDD group. Cortical Cpt1a and Htr1b mRNAs were increased in male offspring of the VDD group. Moreover, cortical 5mC content was reduced in offspring of VDD-fed dams. The additional experiment showed that serum folate and cortical S-adenosylmethionine (SAM) contents were decreased in the offspring of the VDD group. Folic acid supplement attenuated VDD-induced SAM depletion and reversed cortical DNA methylation. Moreover, folic acid supplement attenuated VDD-induced upregulation of depression-related genes. In addition, folic acid supplement alleviated maternal VDD-induced depression-like behaviors in adult offspring. These results suggest that maternal VDD induces depression-like behavior in adult offspring by reducing cortical DNA methylation. The gestational folic acid supplement prevents VDD-induced depression-like behavior by reversing cortical DNA hypomethylation in adult offspring. • Gestational vitamin D deficiency induces depression-like behavior in offspring. • Gestational VDD induces cortical DNA hypomethylation of depression-related genes. • Gestational folic acid supplement prevents VDD-induced depression-like behavior. [ABSTRACT FROM AUTHOR]

Veratrazine A (1), a steroidal alkaloid with a unique 6/5/5 triheterocyclic scaffold as the side chain, was isolated from Veratrum stenophyllum, and its structure was established via spectroscopic analyses and X-ray diffraction. A plausible biosynthetic pathway for 1 is proposed. Bioassy exhibits moderate anti-inflammatory activities in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Sarcococca hookeriana var. digyna Franch. has been widely utilized in folk medicine by the Miao people in the southwestern region of China for treating skin sores which may be associated with microbial infection. To investigate the antifungal bioactivity of S. hookeriana var. digyna against fluconazole-resistant Candida albicans in vitro and in vivo , as well as its underlying mechanism and the key bioactive component. The antifungal bioactivity of 80% ethanol extract of S. hookeriana var. digyna (SHE80) was investigated in vitro using the broth microdilution method, time-growth curve, and time-kill assay. Its key functional component and antifungal mechanism were explored with combined approaches including UPLC-Q-TOF-MS, network pharmacology and metabolomics. The antifungal pathway was further supported via microscopic observation of fungal cell morphology and examination of its effects on fungal biofilm and cell membranes using fluorescent staining reagents. In vivo assessment of antifungal bioactivity was conducted using a mouse model infected with C. albicans on the skin. S. hookeriana var. digyna suppressed fluconazole-resistant C. albicans efficiently (MIC = 16 μg/mL, MFC = 64 μg/mL). It removed fungal biofilm, increased cell membrane permeability, induced protein leakage, reduced membrane fluidity, disrupted mitochondrial membrane potential, induced the release of reactive oxygen species, promoted cell apoptosis, and inhibited the transformation of fungi from the yeast state to the hyphal state significantly. In terms of mechanism, it affected sphingolipid metabolism and signaling pathway. Moreover, the predicted bioactive component, sarcovagine D, was supported by antifungal bioactivity evaluation in vitro (MIC = 4 μg/mL, MFC = 16 μg/mL). Furthermore, S. hookeriana var. digyna promoted wound healing, reduced the number of colony-forming units, and reduced inflammation effectively in vivo. The traditional use of S. hookeriana var. digyna for fungal skin infections was supported by antifungal bioactivity investigated in vitro and in vivo. Its mechanism and bioactive component were predicted and confirmed by experiments, which also provided a new antifungal agent for future research. [Display omitted] • S. hookeriana var. digyna eradicated biofilm, induced cell membrane damage, inhibited fungal morphological transformation. • Sphingolipid metabolism and signaling inhibition identified as key antifungal pathways. • Sarcovagine D, a component of S. hookeriana var. digyna , demonstrated potent antifungal bioactivity for the first time. • The folk use of this plant for detoxifying and healing ulcers was validated by animal experiment. [ABSTRACT FROM AUTHOR]

1-Nitropyrene (1-NP) is a neurodevelopmental toxicant. This study was to evaluate the impact of exposure to 1-NP after weaning on anxiety-like behavior. Five-week-old mice were administered with 1-NP (0.1 or 1 mg/kg) daily for 4 weeks. Anxiety-like behaviour was measured using elevated-plus maze (EPM) and open field test (OFT). In EPM test, time spending in open arm and times entering open arm were reduced in 1-NP-treated mice. In OFT test, time spent in the center region and times entering the center region were diminished in 1-NP-treated mice. Prefrontal dendritic length and number of dendrite branches were decreased in 1-NP-treated mice. Prefrontal PSD95, an excitatory postsynaptic membrane protein, and gephyrin, an inhibitory postsynaptic membrane protein, were downregulated in 1-NP-treated mice. Further analysis showed that peripheral steroid hormones, including serum testosterone (T) and estradiol (E 2), testicular T, and ovarian E 2 , were decreased in 1-NP-treated mice. Interestingly, T and E 2 were diminished in 1-NP-treated prefrontal cortex. Prefrontal T and E 2 synthases were diminished in 1-NP-treated mice. Mechanistically, GCN2-eIF2α, a critical pathway that regulates ribosomal protein translation, was activated in 1-NP-treated prefrontal cortex. These results indicate that exposure to 1-NP after weaning induces anxiety-like behaviour partially by inhibiting steroid hormone synthesis in prefrontal cortex. [Display omitted] • Adolescent exposure to 1-nitropyrene (1-NP) induces anxiety-like behavior. • 1-NP reduces dendritic length and synaptic proteins in prefrontal cortex. • 1-NP reduces steroid hormone synthases and steroid hormones in prefrontal cortex. • GCN2-eIF2α signal mediates 1-NP-evoked reduction of steroid hormone synthases. • Prefrontal steroid hormone reduction mediates 1-NP-evoked anxiety-like behavior. [ABSTRACT FROM AUTHOR]

Three new steroidal alkaloids, veratrasines A − C (1 – 3) , along with ten known analogues (4 – 13) were isolated from the roots of Veratrum stenophyllum. Their structures were elucidated by NMR and HRESIMS data and comparison with the reported data in the literatures. A plausible biosynthetic pathway for 1 and 2 were proposed. Compounds 1 , 3 , and 8 showed moderate cytotoxic activity against MHCC97H and H1299 cell lines. Three new steroidal alkaloids, veratrasines A − C (1 – 3) , along with ten known analogues (4 – 13) were isolated from the roots of Veratrum stenophyllum. Their structures were elucidated via spectroscopic analyses and comparison with the reported data. Compounds 1 , 3 , and 8 showed moderate cytotoxic activity against MHCC97H and H1299 cell lines. [Display omitted] [ABSTRACT FROM AUTHOR]

The abuse of antibiotics leads to the rapid spread of bacterial resistance, which seriously threatens human life and health. Now, 8 resorcylic acid derivatives, including 4 new compounds (1 – 4) were isolated from Lysimachia tengyuehensis by bio-guided isolation, and they inhibited both methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) (MIC = 4–8 μg/mL). Notably, 1 and 2 rapidly killed MRSA and VRE within 40 min without drug resistance in 20 days. Mechanically, they potently disrupted biofilm and cell membrane by interfering with bacterial metabolic imbalance. The structure-activity relationship (SAR) revealed that the lipophilic long carbon chains (C-5/C-6) and hydrophilic hydroxyl/carboxyl groups were essential for the anti-MRSA and VRE bioactivity. Additionally, they effectively recovered MRSA-infected skin wounds and VRE-infected peritoneal in vivo. Resorcylic acid derivatives showed significant anti-MRSA and VRE bioactivity in vitro and in vivo with potential application for the first time. [Display omitted] • Resorcylic acid derivatives from Lysimachia tengyuehensis as major bioactivity rapidly killed MRSA and VRE within 40 min. • Resorcylic acid derivatives disrupted bacterial biofilm and cell membrane homeostasis by interfering with bacterial metabolic imbalance. • Resorcylic acid derivatives might be bactericides with potent applications in treating skin and peritoneal infections. [ABSTRACT FROM AUTHOR]

We present a user-friendly software for photonic analog quantum computing with a graphical user interface (GUI) that allows for convenient operation without requiring programming skills. Hamiltonians can be flexibly set by either importing the waveguide position files or manually plotting the configuration on the interactive board of the GUI. Our software provides a powerful approach to theoretical studies of two-dimensional quantum walks, quantum stochastic walks, multiparticle quantum walks, and boson sampling, which may all be feasibly implemented in the physical experimental system on photonic chips, and it will inspire a rich diversity of applications for photonic quantum computing and quantum simulation. We have improved algorithms to ensure the efficiency of permanent calculation and provided case studies on educational uses, which bring users easier access to the studies of photonic quantum simulation. [ABSTRACT FROM AUTHOR]

Abstract: The compositional variation and the microstructural evolution in laser additive manufactured Ti/Ti–6Al–2Zr–1Mo–1V graded structural material were investigated. An anomalous compositional variation and its good correlation with hardness were found. Although, during the forming process, the ratio of Ti–6Al–2Zr–1Mo–1V in feeded powders abruptly changes from 0% to 100%, all the elements exhibit a gradual variation, which is preferred to a graded material because such gradient change can decrease the discontinuity of its microstructures and properties and can remarkably reduce the costs due to the simplified manufacturing process and the rational distribution of materials. [Copyright &y& Elsevier]

Background: Litter size is an important factor that significantly affects the development of the sheep industry. Our previous TMT proteomics analysis found that three key proteins in the ovarian steroidogenesis pathway, STAR, HSD3B1, and CYP11A1, may affect the litter size trait of Small Tail Han sheep. Objective: The purpose of this study was to better understand the relationship between polymorphisms of these three genes and litter size. Material and Method: Sequenom MassARRAY detected genetic variance of the three genes in 768 sheep. Real‐time qPCR of the three genes was used to compare their expression in monotocous and polytocous sheep in relevant tissues. Finally, bioinformatics analysis predicted the protein sequences of the different SNP variants. Result: Association analysis showed that there was a significant difference in litter size among the genotypes at two loci of the CYP11A1 gene (p < 0.05), but no significant difference was observed in litter size among all genotypes at all loci of the STAR and HSD3B1 genes (p > 0.05). However, STAR expression was significantly different in polytocous and monotocous sheep in the pituitary (p < 0.01). Tissue‐specific expression in the ovary was observed for HSD3B1 (p < 0.05), but its expression was not different between polytocous and monotocous sheep. Bioinformatics analysis showed that the g.33217408C > T mutation of CYP11A1 resulted in major changes to the secondary and tertiary structures. In contrast, gene polymorphisms in STAR and HSD3B1 had minimal impacts on their protein structures. Discussion: This may explain why the CYP11A1 variant impacted litter size while the others did not. The single nucleotide polymorphism of the CYP11A1 gene would serve as a good molecular marker when breeding to increase litter size in sheep. Our study provides a basis for further revealing the function of the ovarian steroidogenesis pathway in sheep reproduction and sheep breeding. [ABSTRACT FROM AUTHOR]

Google PageRank is a prevalent algorithm for ranking the significance of nodes or websites in a network, and a recent quantum counterpart for PageRank algorithm has been raised to suggest a higher accuracy of ranking comparing to Google PageRank. The quantum PageRank algorithm is essentially based on quantum stochastic walks and can be expressed using Lindblad master equation, which, however, needs to solve the Kronecker products of an O( N 4 ) dimension and requires severely large memory and time when the number of nodes N in a network increases above 150. Here, we present an efficient solver for quantum PageRank by using the Runge-Kutta method to reduce the matrix dimension to O( N 2 ) and employing TensorFlow to conduct GPU parallel computing. We demonstrate its performance in solving quantum stochastic walks on Erdös-Rényi graphs using an RTX 2060 GPU. The test on the graph of 6000 nodes requires a memory of 5.5 GB and time of 223 s, and that on the graph of 1000 nodes requires 226 MB and 3.6 s. Compared with QSWalk , a currently prevalent Mathematica solver, our solver for the same graph of 1000 nodes reduces the required memory and time to only 0.2% and 0.05%. We apply the solver to quantum PageRank for the USA major airline network with up to 922 nodes, and to quantum stochastic walk on a glued tree of 2186 nodes. This efficient solver for large-scale quantum PageRank and quantum stochastic walks would greatly facilitate studies of quantum information in real-life applications. [ABSTRACT FROM AUTHOR]

The citrus herbs have proved their important medicinal and nutritional values as medicine–food dual‐purpose herbs, functional foods, or medical herbs in China. In this study, phytochemicals and antioxidant activity among ten typical citrus herbs (ethanol extracts) were investigated comprehensively. The major ingredients and their contents were analyzed by high‐resolution mass spectrometry, and the differences of typical fragment ions between flavanone‐7‐O‐rutinoside(s) and flavanone‐7‐O‐neohesperidoside(s) were discriminated properly in negative electrospray ionization mode. Total polyphenols, total flavonoids, 1,1‐diphenyl‐2‐picrylhydrazyl, 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulphonic acid), and ferric reducing antioxidant power tests were performed, which indicated their beneficial values and antioxidant effects. The medicine–food dual‐purpose herbs including Chenpi, Juluo, Daidaihua, Huajuhong, Xiangyuan, and Foshou exhibited antioxidant capacities significantly by decreasing intracellular reactive oxygen species intensity (P < 0.01), enhancing superoxide dismutase, catalase, and glutathione peroxidase activities (P < 0.01) in H2O2‐induced RIN‐m5F cells. Moreover, the functional foods Zhishi, Zhiqiao, and Qingpi showed moderate antioxidant bioactivity, while the medical herb Juhe showed weak antioxidant bioactivity, which were consistent with the multivariate analysis of their major flavonoids. The study provided a new sight for the chemical differentiation and practical application of citrus herbs as medicine–food dual‐purpose herbs, functional foods, or medical herbs. [ABSTRACT FROM AUTHOR]

Factor that binds to the inducer of short transcripts of the human immunodeficiency virus-1 (FBI-1) represents as a crucial gene regulator in colorectal cancer; however, the correlation between FBI-1 and preoperative radiotherapy (RT) in rectal cancer (RC) has not yet been reported. The aim was to detect FBI-1 expression in patients with RC with or without RT, by immunohistochemistry and quantitative polymerase chain reaction, and to analyze its association with clinicopathological features and response to RT. The results from immunohistochemistry analysis (n=139) and reverse transcription-quantitative polymerase chain reaction (n=55) demonstrated that FBI-1 was overexpressed in patients with RC, whether they had received preoperative RT or not. Subsequently, the association between FBI-1 expression, and the clinicopathological features and response to RT in patients with RC was analyzed. Cytoplasmic FBI-1 was upregulated in non-RT (n=77) and RT (n=62) groups (17.7 vs. 74.0%, P<0.001; 41.1 vs. 69.4%, P=0.002, respectively) of patients with RC compared with normal mucosa. However, nuclear FBI-1 was downregulated (75.8 vs. 22.1%, P<0.001; 83.9 vs. 35.5%, P<0.001, respectively) in both groups. RT had no significant effect on FBI-1 expression in RC tissues. Furthermore, nuclear FBI-1 was positively associated with tumor-node-metastasis stage and distant recurrence (P=0.003 and P=0.010, respectively). In patients with stage I, II or III RC, higher nuclear FBI-1 expression was associated with poorer disease-free survival [hazard ratio (HR)=1.934, 95% confidence interval (CI): 1.055–3.579, P=0.033] and overall survival (HR=2.174, 95% CI: 1.102–4.290, P=0.025), independently of sex, age, growth pattern, differentiation and RT. In addition, FBI-1 was positively correlated with numerous biological factors, including p73 [Spearman's correlation coefficient (rs)=0.332, P=0.007], lysyl oxidase (rs=0.234, P=0.043), Wrap53 (rs=−0.425, P=0.0002) and peroxisome proliferator-activated receptor δ (rs=−0.294, P=0.026). In conclusion, the present study demonstrated that nuclear FBI-1 was an independent prognostic factor in patients with RC and correlated with numerous biological factors, which indicated that it may have multiple roles in RC. [ABSTRACT FROM AUTHOR]

1-Nitropyrene (1-NP), a typical nitro-polycyclic aromatic hydrocarbon, is a developmental toxicant. This study was to evaluate gestational 1-NP-induced anxiety-like behavior in male adult offspring. Pregnant mice were orally administered to 1-NP daily throughout pregnancy. Anxiety-like behaviors, as determined by Elevated Plus-Maze (EPM) and Open-Field Test (OFT), were showed in male adult offspring whose mothers were exposed to 1-NP. Gestational 1-NP exposure reduced dendritic arborization, dendritic length and dendritic spine density in ventral hippocampus of male adult offspring. Additional experiments showed that gephyrin, an inhibitory synaptic marker, was reduced in fetal forebrain and hippocampus in male adult offspring. Nrg1 and Erbb4, two gephyrin-related genes, were reduced in 1-NP-exposed fetuses. Accordingly, 5hmC contents in two CpG sites (32008909 and 32009239) of Nrg1 gene and three CpG sites (69107743, 69107866 and 69107899) of Erbb4 gene were decreased in 1-NP-exposed fetuses. Mechanistically, ten-eleven translocation (TET) activity and alpha-ketoglutarate (α-KG) content were decreased in 1-NP-exposed fetal forebrain. Supplementation with α-KG alleviated 1-NP-induced downregulation of gephyrin-related genes, prevented hippocampal synaptic damage, and improved anxiety-like behavior in male adult offspring. These results indicate that early-life 1-NP exposure causes anxiety-like behavior in male adulthood partially by altering hippocampal epigenetic reprogramming of synaptic plasticity. [Display omitted] • Gestational 1-NP exposure induces anxiety-like behavior in male adult offspring. • 1-NP impairs hippocampal synaptic plasticity. • 1-NP reduces 5hmC of inhibitory synaptic related genes by inhibiting TET activity. • α-KG reverses epigenetic reprogramming of hippocampal synaptic plasticity. • α-KG alleviates 1-NP-induced anxiety-like behavior in male adult offspring. [ABSTRACT FROM AUTHOR]

Allium chinense G. Don is a popular medicinal and aromatic plant, known as "Ganoderma of vegetables" in history for treating blood stasis syndrome that reduces red blood cell oxygen-carrying capacity and often causes severe brain damage. However, the effect of A. chinense on cerebral anoxia remains obscure. Here, the anti-hypoxic effect of A. chinense was investigated for the first time through the cerebral anoxia model of mice. Subsequent a bio-guided investigation brought about the isolation of 16 compounds, including 9 phenolic derivatives (2 new compounds (compound 1, 8) and one new natural product (compound 2), 4 steroidal saponins and 3 fatty acid monoglycerides, among which, 6 compounds (1–4 , 7 , 16) exhibited significant anoxia-tolerant activity in vitro. Moreover, the release of reactive oxygen species (ROS) was decreased significantly, and glutathione (GSH) and lactate dehydrogenase (LDH) were regulated by the 6 bioactive compounds in oxygen‑glucose deprivation/ reoxygenation (OGD/R)-induced BV-2 cells damage. Besides that, protein expressions of HIF-1 α , NLRP3, COX-2, NF- κ B p65 and IL-18 were suppressed effectively. The investigation provided a new nutritional strategy for A. chinense against cerebral anoxia and altitude illness, which might be partially mediated by downregulating NLRP3/NF- κ B. [Display omitted] • The anoxia-tolerant activity of A. chinense was studied for the first time. • Bio-guided investigation led to the isolation of 16 compounds, including three new compounds. • Bioactive compounds improved anoxia-tolerant ability may be associated to regulating NLRP3/NF- κ B. • It may be a source for sustainable foods, dietary supplements and pharmaceutical use. [ABSTRACT FROM AUTHOR]

Aims To investigate the antitumor effects of 7- O -geranylquercetin (GQ), a novel O -alkylated derivative of quercetin, against non-small cell lung cancer (NSCLC) cell lines A549 and NCI-H1975 and the corresponding mechanisms. Main methods Cell viability was assessed using MTT assay. The expression of proteins involved in apoptosis and autophagy was measured using western blotting. Besides, apoptosis was determined with DAPI staining, Annexin V-PI staining and transmission electron microscopy (TEM) assay, and autophagy was observed with TEM assay. Cell cycle and reactive oxygen species (ROS) level were detected using flow cytometry. Key findings GQ inhibited viability of A549 and NCI-H1975 cells in a dose- and time-dependent manner without apparent cytotoxicity to normal human lung fibroblast cells. GQ down-regulated the expression of apoptosis-related proteins pro-caspase 3 and Bcl-2, and up-regulated the expression of cleaved-PARP and Bax in A549 and NCI-H1975 cells. Meanwhile, GQ-induced cell apoptosis could be attenuated by caspase inhibitor Z-VAD-FMK. Besides, GQ induced autophagosome formation in A549 and NCI-H1975 cells, promoted the expression of autophagy-related proteins LC3-II and Beclin 1, and suppressed the expression of p62. Autophagy inhibition with chloroquine or Beclin 1 siRNA could effectively inhibit GQ-induced apoptosis. Furthermore, GQ treatment increased the generation of ROS, and ROS inhibitor N -acetylcysteine could reverse GQ-induced autophagy and apoptosis. Taken together, GQ could induce apoptosis and autophagy via ROS generation in A549 and NCI-H1975 cells, and GQ-induced autophagy contributed to apoptosis. Significance Our findings highlight that GQ is a promising anticancer agent for the treatment of lung cancer. [ABSTRACT FROM AUTHOR]

The interactions between water molecules and aromatic rings are known to be common and important in physics, chemistry and life sciences. Benzene–water complexes are the main prototype systems for O–H…π and lone-pair (lp)…π interactions in theoretical research, however solid state examples are very rare. Here, the solid state example of water sandwiched by a pair of aromatic rings is observed in a silver-mellitate framework, where lp…π and O–H…π interactions coexist. The coexistence of these two interactions has been further verified by theoretical calculations. In addition, ammonium ions and water molecules as proton sources, and strongly H-bonded nets as the pathway of proton transport, make the reported MOFs (metal–organic frameworks) exhibit distinct proton conduction. [ABSTRACT FROM AUTHOR]

A phytochemical investigation of the whole plants of T. delavayi led to the isolation of five new dimeric benzylisoquinoline alkaloids, thalidelavines A–E (1 – 5), together with six known congeners (6 – 11). The structures and absolute configurations of new compounds were established based on analyses of spectroscopic data, ECD calculations, and single crystal X-ray crystallography. Thalidelavines A–E (1 – 5) were structurally complex bisbenzylisoquinoline alkaloids with various configurations. These isolated alkaloids were evaluated for their cytotoxic and immunosuppressive effects. Among them, both 9 and 10 displayed significant cytotoxicities against T98G cell lines with an IC 50 value of 2.1 μM, compared with the positive CPT-11 (IC 50 = 3.0 μM). In addition, 5 – 7 showed remarkable immunosuppressive effects. These findings not only enrich the structural diversity of bisbenzylisoquinoline alkaloids, but also provide potential candidates for the further development of the antitumor and immunosuppressive agents. [Display omitted] [ABSTRACT FROM AUTHOR]

We report here an ultrasensitive strategy based on the recognition-induced conformational alteration of aptamer and fluorescence turn-on abilities of guanine-rich (G-rich) DNA sequence in proximity to silver nanoclusters for adenosine triphosphate (ATP), adenosine (A) and thrombin (TB) detection. Herein, we designed two tailored DNA sequences noted as complementary DNA (abbreviated as c-DNA) and signal probe DNA (abbreviated as s-DNA), respectively. c-DNA is designed as a special structure consisting of a sequence complementary to aptamer at the 3′-end and a guanine-rich DNA sequence at the 5′-end; s-DNA contains a cytosine-rich sequence responsible for Ag NCs templated synthesis at the 3′-end and a link sequence (part of aptamer) complementary to partial of the c-DNA at the 5′-end. In the presence of target, the aptamer associated with the target, resulting in the formation of duplex DNA (dsDNA), the DNA–Ag NCs thereafter could close to the guanine-rich sequence, leading to enhanced fluorescence signal readout. The widespread application of the sensing system is achieved success in the detection of three biomolecules. ATP, adenosine and thrombin in the range of 0.5-8.0 μM, 0.5-7.0 μM and 50-900 nM could be linearly detected with the detection limits of 91.6 nM, 103.4 nM and 8.4 nM, respectively. This label-free and turn-on fluorescent sensing system employing the mechanism proposed here turns out to be sensitive, selective, and convenient for the detection of biomolecules without washing and separation steps. [ABSTRACT FROM AUTHOR]

Lysinespecific demethylase 1 (LSD1), the first identified histonedemethylase, plays an important role in epigenetic regulation of geneactivation and repression. The up-regulated LSD1’s expressionhas been reported in several malignant tumors. In the current study,we designed and synthesized five series of 1,2,3-triazole–dithiocarbamatehybrids and screened their inhibitory activity toward LSD1. We foundthat some of these compounds, especially compound 26,exhibited the most specific and robust inhibition of LSD1. Interestingly,compound 26also showed potent and selective cytotoxicityagainst LSD1 overexpressing gastric cancer cell lines MGC-803 andHGC-27, as well as marked inhibition of cell migration and invasion,compared to 2-PCPA. Furthermore, compound 26effectivelyreduced the tumor growth bared by human gastric cancer cells in vivowith no signs of adverse side effects. These findings suggested thatcompound 26deserves further investigation as a leadcompound in the treatment of LSD1 overexpressing gastric cancer. [ABSTRACT FROM AUTHOR]

A C3-symmetric Schiff-base example of the new simple, low cost, highly water soluble, and sensitive turn-on fluorescent Zn2+ chemosensor is described. The sensor was successfully applied to the detection of intracellular Zn2+. Moreover, the sensor could also serve as a potential recyclable component in sensing materials. Notably, the color change is so obvious that all of the recycling process can be seen clearly by the naked eye. [ABSTRACT FROM AUTHOR]

The root bark of Morus alba Linn. (M. alba), a traditional folk medicine, has been documented in the Chinese Pharmacopoeia, which has been widely used for asthma, fever, pneumonia, edema, vomit, colitis, bronchitis and keratitis diseases. Some of the diseases may be related to respiratory, digestive, urinary tract infections. Although Diels-Alder adducts (DAAs), flavonoids, 2-arylbenzofurans and stilbene compounds have been isolated from the root bark of M. alba , few compounds are reported for their antimicrobial efficacy in viv o and the mechanism. The aim of the study was to isolate and identify compounds of the root bark of M. alba in view of their anti-MRSA bioactivity, evaluate the anti-MRSA bioactivity of compounds and 60% ethanol elution (MA-6) in vitro and in vivo , and explore preliminary antibacterial mechanism in order to provide natural resources against MRSA infection. Systematic phytochemical investigations were carried out according to the thin layer chromatography (TLC) of the active fraction MA-6 to find more anti-MRSA ingredients. The compounds of the root bark of M. alba were separated by column chromatography and identified by LC-MS/MS and NMR spectroscopy. The anti-MRSA efficacy of the active ingredients were evaluated by broth microdilution method and a murine infection model. The mode of action of compounds was explored by time-kill curve and post-contact effect. The preliminary mechanism of compounds against MRSA was explored by drug efflux pumps and bacterial biofilms. Chemical isolation resulted in twenty-nine known compounds, most with one or more geranyl and prenyl units exhibited superior anti-MRSA bioactivity, with MIC values of 2–16 μg/mL. In addition, the mode of action indicated that compounds presented persistent antimicrobial effect, which also produced concentration-dependent and time-dependent killing activity or property. Preliminary mechanism showed that the compound kuwanon O (29) damaged the bacterial cell membranes, leading to the accumulation of antibiotics inside bacterial cells, moreover, MA-6 and kuwanon O (29) inhibited the efflux of drugs by combining with methicillin or ethidium bromide (EtBr), resulting in the MICs of EtBr and methicillin were obviously decreased three-fold. The anti-MRSA efficacy in vivo indicated that the active fraction MA-6 could reduce bacteria in spleen, liver, kidney and mortality of acutely infectious mice, which was better than the positive drug berberine chloride. Experimental investigation showed that the MA-6 and compound 29 have promising bioactivity against MRSA in vitro and in vivo , which might be used as a potential source of new antibacterial medicine or a potential efflux pump inhibitor against MRSA infection. [Display omitted] [ABSTRACT FROM AUTHOR]

Microwavable plastic food containers (MPFCs) are extensively used for food storage, cooking, rapid heating and as take-out containers. There is an urgent need to investigate whether MPFCs pose potential health risks, as a result of the migration of chemicals into foods. Herein, 42 intentionally added substances (IAS) and > 100 non-IAS (NIAS) migrating from MPFCs were identified in food simulants according to Regulation (EU). The migration of major IAS and NIAS was higher in 95% ethanol compared to other simulants, and gradually decreased following repeated use. NIAS, including Cramer class III toxic compounds, such as PEG oligomers of N,N -bis(2-hydroxyethyl) alkyl(C8–C18)amines, isomers of hexadecanamide and oleamide, and Irgafos 168 OXO were detected and exceeded the recommended limits in some MPFCs. Furthermore, microplastics (MPs) were detected with high values of over one million particles/L in some MPFCs in a single test, and migration behaviors of MPs in different MPFCs were diverse. Surprisingly, this rigorous migration might result in an annual intake of IAS/NIAS up to 55.15 mg and 150 million MPs particles if take-out food was consumed once a day. Multi-safety evaluation studies on the migration of various chemicals from MPFCs to foodstuffs during food preparation should be assessed. [Display omitted] • IAS/NIAS and MP can migrate from MPFCs to food simulants. • 42 IAS and over 100 NIAS were identified and quantified in MPFCs. • MPs were detected over one million particles/L in some MPFCs. [ABSTRACT FROM AUTHOR]

Glioblastoma multiform (GBM) is the highly aggressive brain tumor with poor prognosis. Glioma stem cells (GSCs), small population of cancer cells that exist in GBM tissues, resistant to chemotherapy and radiotherapy and usually driving GBM recurrence, have been developed as effective therapeutic target. Steroidal saponins are one of important resources for anti-tumor agent and may be benefited to selectively clear GSCs. In this report, total of 97 natural steroidal saponins were investigated the relationship among structures/cytotoxicity/selectivity against GSCs, glioma cell lines and human untransformed cells, and revealed that tribulosaponin A was the most potent compound. Further investigation suggested that tribulosaponin A up-regulated the expression of NCF1 and NOX1 to accumulate ROS for triggering apoptosis in GSCs, but not in untransformed cells, and it was further supported by the assay that N -acetyl- l -cysteine (NAC) clearing ROS delayed GSCs apoptosis. Besides, tribulosaponin A damaged GSCs recapturing tumor spheres formation. Image 1 • Discovery the structures/cytotoxicity/selectivity relationship of steroidal saponins. • Hydrophilic substituents at C-7, 17, 22, 27 might influence cytotoxicity and selectivity. • Formation of sugar chain at C-3 might influence cytotoxicity and selectivity. • Tribulosaponin A was the most potent molecules selectively against GSCs. • ROS selective accumulation partly resulted in GSCs apoptosis. [ABSTRACT FROM AUTHOR]

Abstract: Hydrothermal reaction of Sr(II) salt with the promising multifunctional organic ligand, 2-(3,4-methylenedioxyphenyl)-1H-imidazole-4,5-dicarboxylic acid (MDPhH3IDC), leads to one new Sr(II) polymer, namely [Sr(MDPhH2IDC)2(H2O)3]n (1), which has been structurally characterized by elemental analysis, IR spectrum, and single crystal X-ray diffraction analysis. In polymer 1, the Sr(II) atoms are linked by water ligands to develop many 1-D chains. These chains are further joined by the MDPhH2IDC− ligands to build up a fascinating 3-D structure. Interestingly, the polymer contains many dinuclear Sr(II) clusters as secondary building blocks. The thermal and photoluminescence properties of the polymer have been investigated as well. [Copyright &y& Elsevier]

Abstract: Two-detector coincidence system and mono-energetic slow positron beam has been applied to measure the Doppler broadening spectra for single crystals of SiO2, SiO2 films with different thickness thermally grown on single crystal of Cz–Si, and single crystal of Si without oxide film. Oxygen is recognized as a peak at about 11.85×10−3 m 0 c on the ratio curves. The S parameters decrease with the increase of positron implantation energy for the single crystal of SiO2 and Si without oxide film. However, for the thermally grown SiO2–Si sample, the S parameters in near surface of the sample increase with positron implantation energy. It is due to the formation of silicon oxide at the surface, which lead to lower S value. S and W parameters vary with positron implantation depth indicate that the SiO2–Si system consist of a surface layer, a SiO2 layer, a SiO2–Si interface layer and a semi-infinite Si substrate. [Copyright &y& Elsevier]

In this paper, a wet-chemical based method was adopted to acquire the uniform dispersion of graphene nanosheets (GNSs) in a powder metallurgy nickel-based superalloy (FGH96) to fabricate a new GNSs reinforced FGH96 metal matrix composite. The surface of the FGH96 powder was modified using a hydrophilic surfactant named polyvinyl alcohol (PVA), which has good wettability and strong hydrogen bonding between the –OH groups of PVA and oxygen groups of GNSs such as –COOH, –CHO, and –OH. It was shown that the GNSs displayed much better dispersion uniformity on the PVA modified FGH96 powder than the unmodified one. The existence of PVA improved the adsorptive capacity of the GNSs attached on the powder surface and prevented the agglomeration in the following thermal preparation process. Consequently, the micro-hardness of PVA modified composite with 0.1 wt.% GNSs reached 497.9 HV, 3.4% higher than the unmodified FGH96 alloy. Therefore, this preparation process could act as the foundation of a common strategy for the fabrication of GNSs in metal matrix composites with good dispersion uniformity, which may have great potential application in aerospace applications. [ABSTRACT FROM AUTHOR]