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Surface-enhanced Raman scattering (SERS) is a powerful, highly efficient analytical technique capable of providing label-free, non-invasive, rapid, and ultrasensitive molecular detection down to the single-molecule level. Despite its advantages, SERS remains largely confined to laboratory settings due to the complexities of substrate fabrication and challenges in analyzing real-world samples. Developing flexible SERS substrates that achieve both high fabrication efficiency and high sensing performance, while being practical for field applications, is critical for advancing SERS toward broader, real-world use. In this study, we present a novel paper-based Ag dendritic SERS chip, fabricated via a simple chemical reduction process that directly forms Ag dendritic nanostructures on cellulose fibers. This chip substrate demonstrates exceptional sensitivity for the detection of thiram pesticide, with a detection limit as low as 7.76 × 10 -11 M. The chip substrate also exhibits outstanding reliability, with reproducibility and repeatability both less than 5%. Furthermore, the flexible nature of the paper substrate enables it to conform to curved surfaces and be in direct contact with analytes, exemplified by its ability to adhere to and retrieve thiram from pear skin using a novel "paste-and-peel-off" technique. The substrate shows remarkable performance for thiram detection on pear skin, with sharp recovery rates ranging from 90% to 105%. With its facile fabrication, excellent sensitivity, high reliability, and practical applicability in non-invasive sampling, the paper-based Ag dendritic SERS substrate offers significant potential as an advanced substrate to bring SERS out of the laboratory and closer to real-world applications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

The calcium release activated calcium (CRAC) channel is highly expressed in T lymphocytes and plays a critical role in regulating T cell proliferation and functions including activation of the transcription factor nuclear factor of activated T cells (NFAT), cytokine production and cytotoxicity. The CRAC channel consists of the Orai pore subunit and STIM (stromal interacting molecule) endoplasmic reticulum calcium sensor. Loss of CRAC channel mediated calcium signaling has been identified as an underlying cause of severe combined immunodeficiency (SCID), leading to drastically weakened immunity against infections. Gain-of-function mutations in Orai and STIM have been associated with tubular aggregated myopathy (TAM), a skeletal muscle disease. While a number of small molecules have shown activity in inhibiting the CRAC signaling pathway, the usefulness of those tool compounds is limited by their off-target activity against TRPM4 and TRPM7 ion channels, high lipophilicity, and a lack of understanding of their mechanism of action. We report structure-activity relationship (SAR) studies that resulted in the characterization of compound 4k [1-(cyclopropylmethyl)-N-(3-fluoropyridin-4-yl)-1H-indazole-3-carboxamie] as a fast onset, reversible, and selective CRAC channel blocker. 4k fully blocked the CRAC current (IC 50 : 4.9 μM) and the nuclear translocation of NFAT at 30 and 10 μM, respectively, without affecting the electrophysiological function of TRPM4 and TRPM7 channels. Computational modeling appears to support its direction binding to Orai proteins that form the transmembrane CRACchannel., Competing Interests: Declaration of competing interest All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

In this work, ZnO nanoparticles (NPs) are synthesized using avocado seed extract and annealed at different annealing temperatures from 400 to 800 °C. The morphology of the nanoparticles changes from poly shapes at 400 °C to spherical ones at 800 °C, and particle sizes increase from ∼42 nm to ∼128 nm. The Ag/ZnO@400/FTO memory device exhibits stable resistive switching over 100 cycles and a resistance window of approximately 150. Also, the performance characteristics of ZnO@600 and ZnO@800-based devices are degraded gradually over operating cycles. The concentration of oxygen interstitials (O i ) in ZnO nanoparticles, which may originate from organic residues, decreases as the annealing temperature increases. These O i ions reduced the energy barrier at the interfaces, facilitating electron transport under an external electric field. This study has demonstrated the close correlation between resistive switching characteristics and organic residuals in green synthesized nanoparticles., Competing Interests: The authors have no conflicts to disclose. The XRD, FTIR, Raman, XPS and EDX data of the ZnO@400 sample were reprinted with permission from ref. 40., (This journal is © The Royal Society of Chemistry.)

A flexible, ultrasensitive, and practical SERS chip is presented based on a paper/f-TiO 2 /Ag structure. The chip enhances the self-assembly of Ag nanoparticles on a cellulose fiber matrix, facilitated by smart functionalized TiO 2 nanomaterials (f-TiO 2 ). This design enables superior detection of the hazardous pesticide tricyclazole (TCZ) on crops using an advanced, simple, and efficient analytical method. Despite its straightforward fabrication process via a solvent immersion method, the intrinsic smart surface properties of the TiO 2 bridging material - both hydrophilic and hydrophobic - enable the uniform and dense self-assembly of hydrophilic Ag nanoparticles (NPs) on the cellulose fiber paper substrate. This innovative design provides superior sensing efficiency for TCZ molecules with a detection limit reaching 2.1 × 10 -9  M, a remarkable improvement compared to Paper/Ag substrates lacking f-TiO 2 nanomaterials, which register at 10 -5  M. This flexible SERS substrate also exhibits very high reliability as indicated by its excellent reproducibility and repeatability with relative standard deviations (RSD) of only 5.93% and 4.73%, respectively. Characterized by flexibility and a water-attractive yet non-soluble surface, the flexible Paper/f-TiO 2 /Ag chips offer the convenience of direct immersion into the analytical sample, facilitating seamless target molecule collection while circumventing interference signals. Termed the "dip and dry" technique, its advantages in field analysis are indisputable, boasting in situ deployment, simplicity, and high efficiency, while minimizing interference signals to negligible levels. Through the application of this advanced technique, we have successfully detected TCZ in two high-value crops, ST25 rice and dragon fruit, achieving excellent recovery values ranging from 90 to 128%. This underscores its immense potential in ensuring food quality and safety. As a proof of concept, flexible Paper/f-TiO 2 /Ag SERS chips, with a simple fabrication process, advanced analytical technique, and superior sensing efficiency, bring SERS one step closer to field applications beyond the laboratory., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

In this study, surface-enhanced Raman scattering substrates were investigated by the electrodeposition method to detect low concentrations of pesticides via the electrodeposition method with different agents from silver and gold precursors on APTES-modified ITO glass. A dual-potential method supplied three electrodes and was performed with a nucleation potential of 0.7 V for 2 s and a growth potential of -0.2 V for 500 s. The Ag film produced by the electrodeposition approach has great surface uniformity and good SERS signal amplification for the thiram insecticide at low concentrations. Interestingly, the ITO/APTES/Ag substrate extensively increased the sensitivity than the other investigated ones, thanks to the adequate assistance of amino groups of APTES in the denser and hierarchical deposition of Ag NPs. These observations were additionally elucidated via finite-difference time-domain (FDTD) calculation. For thiram, the detection was set at 10 -8 M with an enhancement factor of up to 3.6 × 10 7 times. Comparing the SERS spectra of thiram at concentrations of 10 -3 , 10 -4 , and 10 -5 M with a relative standard deviation (RSD) of less than 7.0% demonstrates excellent reproducibility of the ITO/APTES/Ag substrate. In addition, the special selectivity of the ITO/APTES/Ag substrate for thiram demonstrates that these nanostructures can identify pesticides with extreme sensitivity.

Introduction and Importance: Primary gastrointestinal stromal tumors of the liver are exceedingly rare entities, presenting diagnostic and therapeutic challenges. The authors present a case of a 64-year-old male with a primary gastrointestinal stromal tumor (GIST) of the liver, emphasizing the importance of comprehensive diagnostic evaluation and multidisciplinary management in such uncommon cases., Case Presentation: The patient presented with persistent hypochondriac pain, leading to the discovery of a hepatic mass. Diagnostic work-ups, including imaging studies and biopsy, confirmed the diagnosis of primary GIST in the liver. Following thorough multidisciplinary consultation, the patient underwent right anterior segmentectomy of the liver, performed by our experienced surgeon. Postoperative pathology confirmed the diagnosis of GIST, and the patient was advised to use adjuvant imatinib., Clinical Discussion: Primary GISTs of the liver pose diagnostic challenges due to their rarity and varied clinical presentations. Imaging modalities, immunohistochemistry, and molecular genotyping are crucial in accurate diagnosis and treatment planning. Surgical resection remains the cornerstone of treatment for localized GISTs, with adjuvant therapy considered based on recurrence risk factors and molecular characteristics., Conclusion: This case highlights the need for multidisciplinary consultation in managing primary GISTs of the liver. Accurate diagnosis, surgical expertise, and personalized adjuvant therapy are crucial for better patient outcomes. Further research is necessary to enhance our understanding of prognostic factors and treatment strategies for these rare tumors., Competing Interests: The author declares no conflicts of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Google Classroom is a virtual education platform created by Google that allows both instructors and learners to actively participate in educational environments inside and outside of the classroom in an innovative way. This research aims to determine how university students perceived the adoption of Google Classroom in writing classes. This research was a convergent parallel mix-methods approach in which data were gathered through a 5-point Likert scale questionnaire and semi-structured interviews. The participants of this study included 130 university students in Vietnam. The results revealed that students expressed their approval of using Google Classroom in writing classes and that they had a positive view since it benefited them greatly in their learning writing process. This study suggests practical implications for language educators to use Google Classroom in writing classes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Aim: Sleep disorders are common in cancer patients and have negative consequences for patient well-being and treatment outcomes. This study aimed to investigate sleep quality and related factors in Vietnamese middle-aged cancer patients., Methods: A cross-sectional study was conducted on 246 middle-aged in-patient cancer patients at Vietnam National Cancer Hospital (VNCH) from 1/2021 to 7/2021. Sleep was measured by the Pittsburgh Sleep Quality Index (PSQI), with a cutoff of 5., Results: The results showed a male/female ratio of 0.85 with an average age of 52. The five most prevalent cancer types were breast, colorectal, lung, and esophagus-stomach cancer, primarily in the late stage and treated with chemotherapy. The prevalence of sleep disturbances was 58.5%. The mean PSQI score was 7.5, with sleep duration and latency of 5.4 h and 1 h, respectively. Approximately 44% of participants reported poor sleep quality, nearly 9% had daytime dysfunction, and 10.6% used sleep medication. The multivariate logistic regression results indicate that people with depression were 8.89 times more likely to have poor sleep than those without depression (95% CI:2.63-28.27, p < .001)., Conclusion: Sleep problems are common among middle-aged people with cancer in Vietnam, especially individuals with depression. It is necessary to have more effective approaches to sleep management for cancer patients with limited resources., (© 2024 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

Fintech development is generally considered as an effective mechanism to promote the consumption of renewable energy sources. The relationship between fintech development and renewable energy consumption have been examined in previous studies. However, the moderating effect of income inequality on this relationship has largely been ignored in the existing literature. As such, this study is conducted to shed light on this moderating effect. Two estimation techniques, including the two-step system generalized method of moments (GMM) and the method of moments quantile regression (MMQR), were used on a sample of 65 countries from 2013 to 2019. Our findings reveal that fintech development plays a vital role in promoting the consumption of renewable energy sources. However, it is crucial to recognize that rising income inequality may hinder the potential positive effects of fintech development on renewable energy consumption. A threshold of income inequality should be maintained to ensure that the positive effect of fintech development on increased renewable energy consumption is not compromised. Policy implications have emerged based on the findings from this study regarding promoting fintech development towards green economic growth and sustainable development., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Vo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In this study, the features of resistive random access memory (RRAM) employing a straightforward Cr/MAPbI 3 /FTO three-layer structure have been examined and clarified. The device displays various resistance switching (RS) behavior at various sweep voltages between 0.5 and 5 V. The RS effect has a conversion in the direction of the SET and RESET processes during sweeping for a number of cycles at a specific voltage. The directional change of the RS processes corresponds to the dominant transition between the generation/recombination of iodide ion and vacancy in the MAPbI 3 perovskite layer and the electrochemical metallization of the Cr electrode under the influence of an electric field, which results in the conductive filament (CF) formation/rupture. At each stage, these processes are controlled by specific charge conduction mechanisms, including Ohmic conduction, space-charge-limited conduction (SCLC), and variable-range hopping (VRH). By identifying the biased voltage and the quantity of voltage sweep cycles, one can take a new approach to control or modulate the pathways for effective charge transport. This new approach is made possible by an understanding of the RS characteristics and the corresponding mechanisms causing the variation of RS behavior in the structure., (© 2023 Wiley-VCH GmbH.)

Flexible surface-enhanced Raman scattering (SERS) sensors have gained significant attention for their practical applications in detecting chemical and biological molecules. However, the fabrication of flexible SERS chips is often complex and requires advanced techniques. In this study, we present a simple and rapid method to design a flexible SERS chip based on polyvinyl alcohol (PVA), cellulose, and silver nanoparticles (AgNPs) using mechanical stirring and drying methods. Benefiting from the abundant hydroxide groups on cellulose, AgNPs easily adhere and distribute evenly on the cellulose surface. The combination of PVA and cellulose forms a bendable film-like SERS chip. This chip allows convenient immersion in liquid analyte samples. We demonstrate its effectiveness by using it to detect the thiram pesticide in apple juice using the "dip and dry" method, achieving an outstanding detection limit of 1.01 × 10 -8  M. The Raman signals on the SERS chips exhibit high repeatability and reproducibility, with relative standard deviation values below 10%. These findings show that the flexible PVA/cellulose/Ag SERS chips is a strong candidate for real-world analysis., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Anh-Tuan Le reports administrative support and equipment, drugs, or supplies were provided by Phenikaa University., (© 2023 The Authors.)

In this work, a series of unsaturated polyester resin (UPRs)/electrochemically exfoliated graphene oxide (e-GO) polymer nanocomposites with different ratios of e-GO (0.05, 0.1, 0.15, and 0.2 wt%) were prepared via an in situ polymerization method. The surface morphology and structural and chemical properties of the original UPR and UPR/e-GO nanocomposites were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), and fourier transform infrared spectroscopy (FTIR). The positive influence of e-GO nanosheets on the mechanical properties, thermal stability, and anti-UV aging performance of UPR/e-GO nanocomposites was demonstrated by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and dynamic mechanical analysis (DMA). The obtained results showed that the incorporation of e-GO nanosheets within the UPR matrix, despite the addition of e-GO at as low as 0.2 wt% comprehensively improves the advanced functional properties of UPR/e-GO nanocomposites as compared to the original UPR. In addition, artificial weathering testing of quartz-based artificial stone using UPR/e-GO 0.2 wt% showed excellent UV-resistant efficiency, supporting the use of e-GO nanosheets as an additive in manufacturing the industrial-scale UPRs-based artificial quartz stone samples for real outdoor applications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Income inequality is a vexing developmental challenge for governments and policymakers as it impedes social transformation and economic growth and development. Meanwhile, promoting financial development is generally regarded as an effective way to achieve inclusive and sustainable growth. This study examines the long-run effects of financial development, economic growth, and their combined effects on income inequality for 12 Asia-Pacific countries from 1990 to 2021. This paper employs various econometric techniques and different financial development proxies to ensure the findings' robustness. The paper also constructs a financial development index using the principal component analysis to fully capture the comprehensive effect of financial development on income inequality. Empirical results reveal that the impact of financial development on income inequality follows the inverted U-shaped relationship - financial development widens income inequality and only reduces income when surpassing its turning point. Findings further reveal that the nonlinear effect of financial development on income inequality is contingent upon the level of per capita income. Thus, policies promoting financial development to reduce income inequality should consider the existing level of per capita income., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Developing highly efficient and durable hydrogen evolution reaction (HER) electrocatalysts is crucial for addressing the energy and environmental challenges. Among the 2D-layered chalcogenides, MoSe 2 possesses superior features for HER catalysis. The van der Waals attractions and high surface energy, however, stack the MoSe 2 layers, resulting in a loss of edge active catalytic sites. In addition, MoSe 2 suffers from low intrinsic conductivity and weak electrical contact with active sites. To overcome the issues, this work presents a novel approach, wherein the in situ incorporated diethylene glycol solvent into the interlayers of MoSe 2 during synthesis when treated thermally in an inert atmosphere at 600 °C transformed into graphene (Gr). This widened the interlayer spacing of MoSe 2 , thereby exposing more HER active edge sites with high conductivity offered by the incorporated Gr. The resulting MoSe 2 -Gr composite exhibited a significantly enhanced HER catalytic activity compared to the pristine MoSe 2 in an acidic medium and demonstrated a superior HER catalytic activity compared to the state-of-the-art Pt/C catalyst, particularly at a high current density beyond ca. 55 mA cm -2 . Additionally, the MoSe 2 -Gr catalyst demonstrated long-term electrochemical stability during HER. This work, thus, presents a facile and novel approach for obtaining an efficient MoSe 2 electrocatalyst applicable in green hydrogen production.

Receptor-interacting serine/threonine kinase 2 (RIPK2) is a vital immunomodulator that plays critical roles in nucleotide-binding oligomerization domain 1 (NOD1), NOD2, and Toll-like receptors (TLRs) signaling. Stimulated NOD1 and NOD2 interact with RIPK2 and lead to the activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPK), followed by the production of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-12/23. Defects in NOD/RIPK2 signaling are associated with numerous inflammatory diseases, including asthma, sarcoidosis, inflammatory bowel disease (Crohn's disease and ulcerative colitis), multiple sclerosis, and Blau syndrome. As RIPK2 is a crucial element of innate immunity, small molecules regulating RIPK2 functions are attractive to establish novel immunotherapies. The increased interest in developing RIPK2 inhibitors has led to the clinical investigations of novel drug candidates. In this review, we attempt to summarize recent advances in the development of RIPK2 inhibitors and degraders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pham, Ghilardi and Sun.)

This study investigated CuO and ZnO nanoparticles and CuO/ZnO nanocomposites in a friendly environment with a low-cost and renewable biosynthesis method. This approach involved using Boehmeria nivea leaf extract to facilitate the growth and formation of nanocomposites with performance-enhancing phytochemicals released during the co-precipitation process. All nanoparticles/nanocomposites explored the microstructure, morphology, and point defects using FTIR, XRD, SEM, and PL characterization techniques. The synthesized CuO and ZnO nanoparticles and CuO/ZnO nanocomposites were evaluated for their antibacterial ability against both bacteria Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Combining different copper and zinc salt ratios creates different arrangements and morphologies between the CuO sheets and the spherical ZnO nanoparticles. The heterojunction of CuO/ZnO samples enhances the antibacterial effects of nanocomposites compared to pure CuO and ZnO nanoparticles. The maximum antibacterial performance was achieved at 250 ppm against E. coli and 500 ppm against S. aureus in CuO50/ZnO50 nanocomposites. This study shows that a green synthesis of CuO/ZnO nanocomposites promises great potential for environmental treatment and biochemical applications., (2022 Published under an exclusive license by the AVS.)

Whole-genome sequencing and genome mining are recently considered an efficient approach to shine more light on the underlying secondary metabolites of Streptomyces . The present study unearths the biosynthetic potential of endophytic SX6 as a promising source of biologically active substances and plant-derived compounds for the first time. Out of 38 isolates associated with Aegiceras corniculatum (L.) Blanco, Streptomyces parvulus SX6 was highly active against Pseudomonas aeruginosa ATCC® 9027™ and methicillin-resistant Staphylococcus epidermidis (MRSE) ATCC® 35984™. Additionally, S. parvulus SX6 culture extract showed strong cytotoxicity against Hep3B, MCF-7, and A549 cell lines at a concentration of 30 μg/ml, but not in non-cancerous HEK-293 cells. The genome contained 7.69 Mb in size with an average G + C content of 72.8% and consisted of 6,779 protein-coding genes. AntiSMASH analysis resulted in the identification of 29 biosynthetic gene clusters (BGCs) for secondary metabolites. Among them, 4 BGCs showed low similarity (28-67% of genes show similarity) to actinomycin, streptovaricin, and polyoxypeptin gene clusters, possibly attributed to antibacterial and anticancer activities observed. In addition, the complete biosynthetic pathways of plant-derived compounds, including daidzein and genistein were identified using genome mining and HPLC-DAD-MS analysis. These findings portray an exciting avenue for future characterization of promising secondary metabolites from mangrove endophytic S. parvulus ., (© 2022 Ngoc Tung Quach et al., published by Sciendo.)

Thiol-mediated uptake is emerging as a powerful method to penetrate cells. Cyclic oligochalcogenides (COCs) have been identified as privileged scaffolds to enable and inhibit thiol-mediated uptake because they can act as dynamic covalent cascade exchangers, i.e., every exchange produces a new, covalently tethered exchanger. In this study, our focus is on the essentially unexplored COCs of higher oxidation levels. Quantitative characterization of the underlying dynamic covalent exchange cascades reveals that the initial ring opening of cyclic thiosulfonates (CTOs) proceeds at a high speed even at a low pH. The released sulfinates exchange with disulfides in aprotic but much less in protic environments. Hydrophobic domains were thus introduced to direct CTOs into hydrophobic pockets to enhance their reactivity. Equipped with such directing groups, fluorescently labeled CTOs entered the cytosol of living cells more efficiently than the popular asparagusic acid. Added as competitive agents, CTOs inhibit the uptake of various COC transporters and SARS-CoV-2 lentivectors. Orthogonal trends found with different transporters support the existence of multiple cellular partners to account for the diverse expressions of thiol-mediated uptake. Dominant self-inhibition and high activity of dimers imply selective and synergistic exchange in hydrophobic pockets as distinguishing characteristics of thiol-mediated uptake with CTOs. The best CTO dimers with hydrophobic directing groups inhibit the cellular entry of SARS-CoV-2 lentivectors with an IC 50 significantly lower than the previous best CTO, below the 10 μM threshold and better than ebselen. Taken together, these results identify CTOs as an intriguing motif for use in cytosolic delivery, as inhibitors of lentivector entry, and for the evolution of dynamic covalent networks in the broadest sense, with reactivity-based selectivity of cascade exchange emerging as a distinguishing characteristic that deserves further attention., Competing Interests: The authors declare the following competing financial interest(s): A U.S. Patent Application has been filed covering the antiviral activities of 3, 4, 11, 15, 33, 35 (No. 63/073,863)., (© 2022 The Authors. Published by American Chemical Society.)

Objectives: Though menstrual and reproductive factors have been associated with the risk of breast cancer in many populations, very few studies have been conducted among Vietnamese women. This study aimed to assess the association between menstrual and reproductive factors and the risk of breast cancer in Vietnamese women., Methods: A retrospective case-control study of 490 breast cancer cases and 468 controls was conducted in Northern Vietnam. Unconditional logistic regression models adjusting for confounders were used to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) for the associations of menstrual and reproductive factors with the risk of breast cancer; overall and by cancer subtype., Results: Among breast cancer patients, the luminal B subtype was the most frequent (48.6%), followed by HER2-overexpressing (24.5%), luminal A (16.7%), and triple-negative breast cancer (TNBC; 10.2%). Among menopausal women, menopausal age at 50 years or older (OR = 1.71, 95% CI: 1.15-2.57 vs. <50 y) was associated with an increased risk of breast cancer. Earlier age at menarche (<13 y) was associated with a significantly increased risk of breast cancer (OR = 2.66, 95% CI: 1.08-7.51) among premenopausal women only and the luminal A subtype of breast cancer (OR = 3.06, 95% CI: 1.04-8.16). Having more than two children was associated with a reduced risk of premenopausal (OR = .42, 95%CI: .21-.83), luminal B (OR = .43, 95% CI: .24-.79), and TNBC (OR = .34, 95% CI: .14-.89). Later menopause was positively associated with the risk of breast cancer with HER2 overexpression (OR = 2.19, 95% CI: 1.14-4.23)., Conclusion: Associations of menstrual and reproductive factors with breast cancer among Vietnamese women, particularly for among premenopausal women and for the luminal A subtype, are generally consistent with those reported from other countries. These findings suggest that changes in menstrual and reproductive patterns among young Vietnamese women may contribute to the recent rising incidence of breast cancer in Vietnam.

This Perspective focuses on thiol-mediated uptake, that is, the entry of substrates into cells enabled by oligochalcogenides or mimics, often disulfides, and inhibited by thiol-reactive agents. A short chronology from the initial observations in 1990 until today is followed by a summary of cell-penetrating poly(disulfide)s (CPDs) and cyclic oligochalcogenides (COCs) as privileged scaffolds in thiol-mediated uptake and inhibitors of thiol-mediated uptake as potential antivirals. In the spirit of a Perspective, the main part brings together topics that possibly could help to explain how thiol-mediated uptake really works. Extreme sulfur chemistry mostly related to COCs and their mimics, cyclic disulfides, thiosulfinates/-onates, diselenolanes, benzopolysulfanes, but also arsenics and Michael acceptors, is viewed in the context of acidity, ring tension, exchange cascades, adaptive networks, exchange affinity columns, molecular walkers, ring-opening polymerizations, and templated polymerizations. Micellar pores (or lipid ion channels) are considered, from cell-penetrating peptides and natural antibiotics to voltage sensors, and a concise gallery of membrane proteins, as possible targets of thiol-mediated uptake, is provided, including CLIC1, a thiol-reactive chloride channel; TMEM16F, a Ca-activated scramblase; EGFR, the epithelial growth factor receptor; and protein-disulfide isomerase, known from HIV entry or the transferrin receptor, a top hit in proteomics and recently identified in the cellular entry of SARS-CoV-2., Competing Interests: The authors declare the following competing financial interest(s): A U.S. Patent Application has been filed covering the antiviral activity of cyclic thiosulfonates (No. 63/073,863)., (© 2021 The Authors. Published by American Chemical Society.)

In vitro and ex vivo development of novel therapeutic agents requires reliable and accurate analyses of the cell conditions they were preclinical tested for, such as apoptosis. The detection of apoptotic cells by annexin V (AV) coupled to fluorophores has often shown limitations in the choice of the dye due to interference with other fluorescent-labeled cell markers. The SNAP-tag technology is an easy, rapid and versatile method for functionalization of proteins and was therefore used for labeling AV with various fluorophores. We generated the fusion protein AV-SNAP and analyzed its capacity for the specific display of apoptotic cells in various assays with therapeutic agents. AV-SNAP showed an efficient coupling reaction with five different fluorescent dyes. Two selected fluorophores were tested with suspension, adherent and peripheral blood cells, treated by heat-shock or apoptosis-inducing therapeutic agents. Flow cytometry analysis of apoptotic cells revealed a strong visualization using AV-SNAP coupled to these two fluorophores exemplary, which was comparable to a commercial AV-Assay-kit. The combination of the apoptosis-specific binding protein AV with the SNAP-tag provides a novel solid method to facilitate protein labeling using several, easy to change, fluorescent dyes at once. It avoids high costs and allows an ordinary exchange of dyes and easier use of other fluorescent-labeled cell markers, which is of high interest for the preclinical testing of therapeutic agents in e.g. cancer research., Competing Interests: The authors have declared that no competing interests exist.

Ellman's reagent has caused substantial confusion and concern as a probe for thiol-mediated uptake because it is the only established inhibitor available but works neither efficiently nor reliably. Here we use fluorescent cyclic oligochalcogenides that enter cells by thiol-mediated uptake to systematically screen for more potent inhibitors, including epidithiodiketopiperazines, benzopolysulfanes, disulfide-bridged γ-turned peptides, heteroaromatic sulfones and cyclic thiosulfonates, thiosulfinates and disulfides. With nanomolar activity, the best inhibitors identified are more than 5000 times better than Ellman's reagent. Different activities found with different reporters reveal thiol-mediated uptake as a complex multitarget process. Preliminary results on the inhibition of the cellular uptake of pseudo-lentivectors expressing SARS-CoV-2 spike protein do not exclude potential of efficient inhibitors of thiol-mediated uptake for the development of new antivirals., Competing Interests: A U.S. Patent application has been filed (No. 63/073863)., (This journal is © The Royal Society of Chemistry.)

We report design, synthesis and evaluation of a series of naphthalenediimides (NDIs) that are bridged with short peptides. Reminiscent of peptide stapling technologies, the macrocycles are conveniently accessible by a chromogenic nucleophilic aromatic substitution of two bromides in the NDI core with two thiols from cysteine sidechains. The dimension of core-bridged NDIs matches that of one turn of an α helix. NDI-stapled peptides exist as two, often separable atropisomers. Introduction of tertiary amine bases in amino-acid sidechains above the π-acidic NDI surface affords operational anion-π catalysts. According to an enolate chemistry benchmark reaction, anion-π catalysis next to peptides occurs with record chemoselectivity but weak enantioselectivity. Catalytic activity drops with increasing distance of the amine base to the NDI surface, looser homocysteine bridges, mismatched, shortened and elongated α-helix turns, and acyclic peptide controls. Elongation of isolated turns into short α helices significantly increases activity. This increase is consistent with remote control of anion-π catalysis from the α-helix macrodipole., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The electrochemical behaviour of auramine O on the hanging mercury drop electrode has been investigated by cyclic and square wave voltammetry method. Reduction peak of auramine O was irreversible and adsorptive on the hanging mercury drop electrode. The optimal conditions were chosen to be Briton-Robinson buffer pH 9.0, accumulation potential -0.5 V vs. Ag/AgCl/KCl, accumulation time 60 s, pulse amplitude 250 mV·s -1 , and frequency 50 Hz. At the optimum experimental conditions, the peak of the target analyte was sharp and asymmetric. The linearity of the peak current depending on the concentration ranged from 4.0 × 10 -8 to 6.4 × 10 -7  mol L -1 . The limit of detection and limit of quantitation were 2.46 × 10 -8  mol L -1 and 8.21 × 10 -8  mol L -1 , respectively. The recovery and relative standard deviation were 94.9% and 2.0% ( n  = 5). The developed method was successfully applied to determine auramine O in chicken samples with an appropriate sample preparation.

Epoxide-opening ether cyclizations are shown to occur on π-acidic aromatic surfaces without the need of additional activating groups and with autocatalytic amplification. Increasing activity with the intrinsic π acidity of benzenes, naphthalenediimides (NDIs) and perylenediimides (PDIs) support that anion-π interactions account for function. Rate enhancements maximize at 270 for anion-π catalysis on fullerenes and at 5100 M -1 for autocatalysis. The occurrence of anion-π autocatalysis is confirmed with increasing initial rates in the presence of additional product. Computational studies on autocatalysis reveal transition state and product forming a hydrogen-bonded noncovalent macrocycle, like holding their hands and dancing on the active π surface, with epoxide opening and nucleophile being activated by anion-π interactions and hydrogen bonds to the product, respectively.

We demonstrate a high-performance photodetector with multilayer tin diselenide (SnSe2) exfoliated from a high-quality crystal which was synthesized by the temperature gradient growth method. This SnSe2 photodetector exhibits high photoresponsivity of 5.11 × 105 A W-1 and high specific detectivity of 2.79 × 1013 Jones under laser irradiation (λ = 450 nm). We also observed a reproducible and stable time-resolved photoresponse to the incident laser beam from this SnSe2 photodetector, which can be used as a promising material for future optoelectronic applications.

Interleukin-6 (IL-6) expression and secretion, induced by inflammatory processes, stimulate the acute phase response cascade. The overexpression of IL-6 contributes to a variety of inflammatory diseases, e.g. rheumatoid arthritis, Castleman's disease, multiple myeloma, and prostate cancer. Screening for high amounts of IL-6 in the patients' blood serum can be crucial for an adequate treatment. In this study, five novel murine monoclonal antibodies (mAbs) reactive to human IL-6 were generated. The mAbs were characterized for potential diagnostic purposes and recombinant antibodies were derived thereof. Initial epitope mapping using a combination of blocking experiments and Hyper-IL-6, a fusion protein consisting of IL-6 and the soluble IL-6 receptor revealed distinct but overlapping binding sites. At least one of the mAbs was found to interact with the region of IL-6/ IL-R complex formation. Three mAbs were applied successfully in intracellular staining by flow cytometry, whereas one of the mAbs showed comparable binding as a reference reagent. Furthermore, the mAbs were tested for applications in various immunological assays such as ELISA, Western blot and surface plasmon resonance spectroscopy (SPR), using IL-6 from commercial sources as well as in-house produced protein (IL-6&#95;IME). The limit of detection was determined by sandwich ELISA (0.5 ng/mL, SD ±0.005). Our results also demonstrated that the recombinant IL-6 produced was functional and correctly folded. These findings support the use of the generated mAb clones as promising candidates for application in various immunological assays for diagnostic and scientific purposes.

Two β-galactosidases from Lactobacillus, including a heterodimeric LacLM type enzyme from Lactobacillus reuteri L103 and a homodimeric LacZ type β-galactosidase from Lactobacillus bulgaricus DSM 20081, were studied for immobilization on chitin using a carbohydrate-binding domain (chitin-binding domain, ChBD) from a chitinolytic enzyme. Three recombinant enzymes, namely, LacLM-ChBD, ChBD-LacLM, and LacZ-ChBD, were constructed and successfully expressed in Lactobacillus plantarum WCFS1. Depending on the structure of the enzymes, either homodimeric or heterodimeric, as well as the positioning of the chitin-binding domain in relation to the catalytic domains, that is, upstream or downstream of the main protein, the expression in the host strain and the immobilization on chitin beads were different. Most constructs showed a high specificity for the chitin in immobilization studies; thus, a one-step immobilizing procedure could be performed to achieve up to 100% yield of immobilization without the requirement of prior purification of the enzyme. The immobilized-on-chitin enzymes were shown to be more stable than the corresponding native enzymes; especially the immobilized LacZ from L. bulgaricus DSM20081 could retain 50% of its activity when incubated at 37 °C for 48 days. Furthermore, the immobilized enzymes could be recycled for conversion up to eight times with the converting ability maintained at 80%. These results show the high potential for application of these immobilized enzymes in lactose conversion on an industrial scale.

We investigated the effect of single and multidopants on the thermoelectrical properties of host ZnO films. Incorporation of the single dopant Ga in the ZnO films improved the conductivity and mobility but lowered the Seebeck coefficient. Dual Ga- and In-doped ZnO thin films show slightly decreased electrical conductivity but improved Seebeck coefficient. The variation of thermoelectric properties is discussed in terms of film crystallinity, which is subject to the dopants' radius. Small amounts of In dopants with a large radius may introduce localized regions in the host film, affecting the thermoelectric properties. Consequently, a 1.5 times increase in power factor, three times reduction in thermal conductivity, and 5-fold enhancement in the figure of merit ZT have been achieved at 110 °C. The results also indicate that the balanced control of both electron and lattice thermal conductivities through dopant selection are necessary to attain low total thermal conductivity.

Transparent conductive electrodes for applications in optoelectronic devices such as solar cells and light-emitting diodes are important components and require low sheet resistance and high transmittance. Herein, we report an enhancement of the electrical properties of silver (Ag) nanowire networks by coating with zinc oxide using the atomic layer deposition technique. A strong decrease in the sheet resistance of Ag nanowires, namely from 20-40 Ω/□ to 7-15 Ω/□, was observed after coating with ZnO. Ag nanowire electrodes coated with 200-cycle ZnO by atomic layer deposition show the best quality, with a sheet resistance of 11 Ω/□ and transmittance of 75%.

Chondroitin sulfate proteoglycan 4 (CSPG4) has been identified as a highly promising target antigen for immunotherapy of triple-negative breast cancer (TNBC). TNBC represents a highly aggressive heterogeneous group of tumors lacking expression of estrogen, progesterone and human epidermal growth factor receptor 2. TNBC is particularly prevalent among young premenopausal women. No suitable targeted therapies are currently available and therefore, novel agents for the targeted elimination of TNBC are urgently needed. Here, we present a novel cytolytic fusion protein (CFP), designated αCSPG4(scFv)-MAP, that consists of a high affinity CSPG4-specific single-chain antibody fragment (scFv) genetically fused to a functionally enhanced form of the human microtubule-associated protein (MAP) tau. Our data indicate that αCSPG4(scFv)-MAP efficiently targets CSPG4(+) TNBC-derived cell lines MDA-MB-231 and Hs 578T and potently inhibits their growth with IC50 values of ∼200 nM. Treatment with αCSPG(scFv)-MAP resulted in induction of the mitochondrial stress pathway by activation of caspase-9 as well as endonuclease G translocation to the nucleus, while induction of the caspase-3 apoptosis pathway was not detectable. Importantly, in vivo studies in mice bearing human breast cancer xenografts revealed efficient targeting to and accumulation of αCSPG4(scFv)-MAP at tumor sites resulting in prominent tumor regression. Taken together, this preclinical proof of concept study confirms the potential clinical value of αCSPG4(scFv)-MAP as a novel targeted approach for the elimination of CSPG4-positive TNBC., (© 2016 UICC.)

SNAP-tag technology allows recombinant proteins to be covalently labeled to O(6)-benzylguanine (BG)-modified substrates with 1:1 stoichiometry. By attaching according fluorophores, this method is ideally suited for in vitro and in vivo imaging, as well as protein interaction analyses. Fluorophores modified with BG react with the SNAP-tag, whereas those modified with O(2)-benzylcytosine (BC) conjugate to a more recent derivative known as the CLIP-tag. The orthogonal substrate specificity of the SNAP- and CLIP-tags extends the range of applications by allowing double labeling. We previously developed a monoclonal antibody (mAb) that recognizes both tags. In this study, we describe a new mAb, which is specific for the SNAP-tag alone. Therefore, this mAb allows discrimination between SNAP- and CLIP-tags within a broad range of immunological methods, including enzyme-linked immunosorbent assays, western blotting, flow cytometry, and immunohistochemistry.

Triple-negative breast cancer (TNBC) is associated with poor prognosis and high prevalence among young premenopausal women. Unlike in other breast cancer subtypes, no targeted therapy is currently available. Overexpression of epithelial cell adhesion molecule (EpCAM) in 60% of TNBC tumors correlates with poorer prognosis and is associated with cancer stem cell phenotype. Thus, selective elimination of EpCAM(+) TNBC tumor cells is of clinical importance. Therefore, we constructed a fully human targeted cytolytic fusion protein, designated GbR201K-αEpCAM(scFv), in which an EpCAM-selective single-chain antibody fragment (scFv) is genetically fused to a granzyme B (Gb) mutant with reduced sensitivity to its natural inhibitor serpin B9. In vitro studies confirmed its specific binding, internalization and cytotoxicity toward a panel of EpCAM-expressing TNBC cells. Biodistribution kinetics and tumor-targeting efficacy using MDA-MB-468 cells in a human TNBC xenograft model in mice revealed selective accumulation of GbR201K-αEpCAM(scFv) in the tumors after i.v. injection. Moreover, treatment of tumor-bearing mice demonstrated a prominent inhibition of tumor growth of up to 50 % in this proof-of-concept study. Taken together, our results indicate that GbR201K-αEpCAM(scFv) is a promising novel targeted therapeutic for the treatment of TNBC., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

In 2008, the Centers for Medicare and Medicaid Service adapted a list from the National Quality Forum consisting of 10 hospital-acquired conditions, also known as never events. Deeming such events as preventable in a safe-hospital setting, reimbursement is no longer provided for treatments arising secondary to these events. A retrospective chart review identified 90 panniculectomy and abdominoplasty patients. The hospital-acquired conditions examined include surgical-site infections (SSI), vascular-catheter associated infections, deep venous thrombosis/pulmonary embolism, retained foreign body, catheter-related urinary tract infection, manifestations of poor glycemic control, falls and trauma, air embolism, pressure ulcers (stages III and IV), and blood incompatibility. Information regarding age, American Society of Anesthesiologists (ASA) classification, body mass index, smoking, and chemotherapy were collected. Patients were divided into 2 groups, namely, those who developed never events and those with no events. Of the 90 patients, 14 (15.5%) developed never events because of SSI. No events occurred in the remaining 9 categories. Statistically significant risk factors included American Society of Anesthesiologists classification, age, and diabetes mellitus. The most common never event was SSI. In light of the obvious prevalence of the risk factors in patients who develop these events, the question of whether never events are truly unavoidable arises. Despite this, awareness of the impact on patient care, health care and hospital reimbursement is vital to understanding the new paradigm of the "one size fits all."

In normal epithelia, the epithelial cell adhesion molecule (EpCAM) expression is relatively low and only present at the basolateral cell surface. In contrast, EpCAM is aberrantly overexpressed in various human carcinomas. Therefore, EpCAM is considered to be a highly promising target for antibody-based cancer immunotherapy. Here, we present a new and fully human cytolytic fusion protein (CFP), designated "anti-EpCAM(scFv)-MAP," that is comprised of an EpCAM-specific antibody fragment (scFv) genetically fused to the microtubule-associated protein tau (MAP). Anti-EpCAM(scFv)-MAP shows potent EpCAM-restricted proapoptotic activity toward rapidly proliferating carcinoma cells. In vitro assays confirmed that treatment with anti-EpCAM(scFv)-MAP resulted in the colocalization and stabilization of microtubules, suggesting that this could be the potential mode of action. Dose-finding experiments indicated that anti-EpCAM(scFv)-MAP is well tolerated in mice. Using noninvasive far-red in vivo imaging in a tumor xenograft mouse model, we further demonstrated that anti-EpCAM(scFv)-MAP inhibited tumor growth in vivo. In conclusion, our data suggest that anti-EpCAM(scFv)-MAP may be of therapeutic value for the targeted elimination of EpCAM(+) carcinomas., (©2014 American Association for Cancer Research.)