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Background: This paper aims to analyse the active components of Semen cuscutae (SC) by network pharmacology and screen the most stable compounds with tumour necrosis factor-alpha (TNF-α) by molecular docking to explore the mechanisms of SC treatment of recurrent spontaneous abortion (RSA) and provide a theoretical basis for drug development.Methods: The active compounds of SC and the potential inflammatory targets of RSA were obtained from the Traditional Chinese Medicine Systems Pharmacology database and GeneCards, respectively. The RSA-SC target gene interaction network was obtained and visualized using the STRING database and Cytoscape software. GO and KEGG pathway enrichment analyses were obtained from DAVID to further explore the RSA mechanism and therapeutic effects of SC. Interactions between TNF-α and drugs were analysed by molecular docking. Treatment of human trophoblast cells with sesamin and TNF-α was carried out to detect their proliferative and apoptotic abilities, and WB assay was carried out to detect EGFR, PTGS2, and CASP3 protein expression.Results: Ten compounds and 128 target genes were screened from SC, of which 79 overlapped with RSA target inflammatory genes, which were considered potential therapeutic targets. Network pharmacological analysis showed that sesamin, matrine, matrol, and other SC compounds had a good correlation with the inflammatory target genes of RSA. Related genes included PGR, PTGS1, PTGS2, TGFB1, and CHRNA7. Several signalling pathways are involved in the pathogenesis of RSA, such as the TNF-α signalling pathway, HIF-1 signalling pathway, oestrogen signalling pathway, proteoglycans in cancer cells, and FoxO signalling pathway. Molecular docking results suggested that sesamin was the most suitable natural tumour necrosis factor inhibitor (TNFi). Sesamin can promote proliferation and inhibit apoptosis in human trophoblasts by downregulating EGFR and CASP3 expression and upregulating PTGS2 expression.Conclusion: Our findings play an important role and basis for further research into the molecular mechanism of SC treatment of RSA and drug development of TNFi.

Abstract Objective This study aims to identify the effect of miR-146a-5p on trophoblast cell invasion as well as the mechanism in preeclampsia (PE). Methods Expression levels of miR-146a-5p and Wnt2 in preeclamptic and normal placentae were quantified. Trophoblast cells (HTR-8) were separately transfected with miR-146a-5p mimic, miR-146a-5p inhibitor, pcDNA3.1-Wnt2 or sh-Wnt2, and then the expression levels of miR-146a-5p, Wnt2, and epithelial-mesenchymal transition (EMT)-related proteins (Vimentin, N-cadherin and E-cadherin) were measured. Moreover, the proliferative, migratory and invasive capacities of trophoblast cells were detected, respectively. Dual luciferase reporter assay determined the binding of miR-146a-5p and Wnt2. Results Compared with normal placental tissues, the placentae from PE patients showed higher miR-146a-5p expression and lower Wnt2 expression. Transfection of miR-146a-5p inhibitor or pcDNA3.1-Wnt2 exerted pro-migratory and pro-invasive effects on HTR-8 cells and encouraged EMT in HTR-8 cells; transfection with miR-146a-5p mimic or sh-Wnt2 weakened the proliferative, migratory and invasive capacities as well as reduced EMT process of HTR-8 cells. Moreover, Wnt2 overexpression could partially counteract the suppressive effects of miR-146a-5p overexpression on the progression and EMT of HTR-8 cells. Conclusion miR-146a-5p mediates trophoblast cell proliferation and invasion through regulating Wnt2 expression.

Abstract Background Peutz–Jeghers syndrome (PJS), a rare dominantly inherited disease, is primarily characterized by hamartomatous polyps and melanotic macules as well as by an increased risk of cancer. The current study aimed to identify the pathogenic gene and pathogenic mechanism of a proband with PJS, thereby offering precise prevention and treatment strategies for PJS. Methods A detailed clinical examination was performed of the proband diagnosed with PJS and her family members. In addition, peripheral venous blood was collected from the family members to extract genomic DNA. The pathogenic genes of the proband were identified using whole-exome sequencing, and the candidate pathogenic variants were verified via Sanger sequencing. Meanwhile, co-segregation tests were performed among six family members. Finally, reverse transcription-polymerase chain reaction (RT-PCR) was performed to assess transcript variants in the peripheral blood cells of patients and non-related healthy controls. Results Genetic testing revealed a rare splicing variant c.921-1G > C in STK11 in the proband and in her sister and nephew, and the variant co-segregated among the affected family members and nonrelated healthy controls. The proband phenotypically presented with a rare gastric-type adenocarcinoma of the cervix. RT-PCR revealed that the STK11 c.921-1G > C variant could produce two transcripts. Of note, 40 base pairs were deleted in the aberrant transcript between exons 3 and 4, resulting in a frameshift variant and premature termination of the amino acid in exon 6 and ultimately leading to the loss of its functional domain in the STK11 protein. Finally, RT-PCR showed that compared with healthy controls, STK11 mRNA expression level was C in intron 7 of STK11 may be a pathogenic variant in patients with PJS. However, this variant (in intron 7) may not produce abnormal transcripts (deletion of 40 base pairs between exons 3 and 4), and PJS may be attributed to the decrease in STK11 expression. Therefore, this study emphasized the importance of genetic counseling, pre-symptomatic monitoring, and early complication management in PJS.

Abstract Palladium films hold signicance due to their remarkable affinity for hydrogen diffusion, rendering them valauble for the seperation and purification of hydrogen in membrane reactors. However, palladium is expensive, and its films can become brittle after only a few cycles of hydrogen separation. Alloying with silver has been shown to overcome the problem of palladium embrittlement. Palladium‐silver films have been produced via several methods but all have drawbacks, such as difficulties controlling the alloy composition. This study explores two promising jet printing methods: Inkjet and Aerosoljet. Both methods offer potential advantages such as direct patterning, which reduces waste, enables thin film production, and allows for the control of alloy composition. For the first time, palladium‐silver alloys have been produced via inkjet printing using a palladium‐silver metal organic decomposition (MOD) ink, which alloys at a temperature of 300 °C with nitrogen. Similarly, this study also demonstrates a pioneering approach for Aerosol Jet printing, showing the potential of a novel room‐temperature method, for the deposition of palladium‐silver MOD inks. This low temperature approach is considered an important development as palladium‐silver MOD inks are originally designed for deposition on heated substrates.

Metabolic reprograming is a hallmark of cancer, and the polyamine metabolic network is dysregulated in many cancers. Ornithine decarboxylase (ODC) is a rate-limiting enzyme for polyamine synthesis in the polyamine metabolic network. In many cancer cells, ODC is over-expressed, so this enzyme has been an attracting anti-cancer drug target. In the catalysis axis (pathway), ODC converts ornithine to putrescine. Meanwhile, ODC's activity is regulated by protein-protein interactions (PPIs), including the ODC-OAZ1-AZIN1 PPI axis and its monomer-dimer equilibrium. Previous studies showed that when ODC's activity is inhibited, the PPIs might counteract the inhibition efficiency. Therefore, we proposed that multipurpose inhibitors that can simultaneously inhibit ODC's activity and perturb the PPIs would be very valuable as drug candidates and molecular tools. To discover multipurpose ODC inhibitors, we established a computational pipeline by combining positive screening and negative screening. We used this pipeline for the forward screening of multipurpose ligands that might inhibit ODC's activity, block ODC-OAZ1 interaction and enhance ODC non-functional dimerization. With a combination of different experimental assays, we identified three multipurpose ODC inhibitors. At last, we showed that one of these inhibitors is a promising drug candidate. This work demonstrated that our computational pipeline is useful for discovering multipurpose ODC inhibitors, and multipurpose inhibitors would be very valuable. Similar with ODC, there are a lot of proteins in human proteome that act as both enzymes and PPI components. Therefore, this work is not only presenting new molecular tools for polyamine study, but also providing potential insights and protocols for discovering multipurpose inhibitors to target more important protein targets. [ABSTRACT FROM AUTHOR]

Chemical imaging (CI) is the spatial identification of molecular chemical composition and is critical to characterising the (in-) homogeneity of functional material surfaces. Nanoscale CI on bulk functional material surfaces is a longstanding challenge in materials science and is addressed here.We demonstrate the feasibility of surface sensitive CI in the scanning electron microscope (SEM) using colour enriched secondary electron hyperspectral imaging (CSEHI). CSEHI is a new concept in the SEM, where secondary electron emissions in up to three energy ranges are assigned to RGB (red, green, blue) image colour channels. The energy ranges are applied to a hyperspectral image volume which is collected in as little as 50 s. The energy ranges can be defined manually or automatically.Manual application requires additional information from the user as first explained and demonstrated for a lithium metal anode (LMA) material, followed by manual CSEHI for a range of materials from art history to zoology.We introduce automated CSEHI, eliminating the need for additional user information, by finding energy ranges using a non-negative matrix factorization (NNMF) based method. Automated CSEHI is evaluated threefold: (1) benchmarking to manual CSEHI on LMA; (2) tracking controlled changes to LMA surfaces; (3) comparing automated CSEHI and manual CI results published in the past to reveal nanostructures in peacock feather and spider silk. Based on the evaluation, CSEHI is well placed to differentiate/track several lithium compounds formed through a solution reaction mechanism on a LMA surface (eg. lithium carbonate, lithium hydroxide and lithium nitride). CSEHI was used to provide insights into the surface chemical distribution on the surface of samples from art history (mineral phases) to zoology (di-sulphide bridge localisation) that are hidden from existing surface analysis techniques. Hence, the CSEHI approach has the potential to impact the way materials are analysed for scientific and industrial purposes.

With the rapid development of social economy, people’s living environment has undergone tremendous changes. At the same time as social development, it will also be accompanied by many problems, such as environmental degradation, air quality decline, and frequent diseases. Studies have found that due to the destruction of the ozone layer, the ultraviolet rays in the atmosphere cannot be effectively absorbed, which hinders the reduction, and the risk of skin cancer increases year by year. Environmental pollution is becoming more and more serious, bacteria multiply, and textiles are also polluted. Every year, a large number of textiles are discarded due to pollution, so people have new demands on the functionality of textiles. In recent years, with the breakthrough development of nanomaterials research enterprises, nanomaterials are increasingly used in textiles to meet people’s new needs for textiles. Nano-TiO2 has high antiultraviolet performance and self-cleaning performance and also has excellent performance in antibacterial and bacteriostatic issues. Toxicological experiments were carried out on nano-TiO2 materials. The results showed that the cytotoxicity of different cells in different concentrations of nano-TiO2 was very small, the cell viability was not less than 80%, and there was a certain concentration effect.