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Natural deep eutectic solvents (NADES) are a type of ionic liquid (IL) or deep eutectic solvent (DES), the ingredients of which are exclusively natural products (non-toxic and environmentally friendly). Here, we explore the potential of NADES as an alternative to conventional organic solvents (e.g., aqueous methanol or ethanol) for the extraction of flavonoids from Scutellaria baicalensis stem bark to investigate their extractability depending on structural variation. Four NADES, each containing citric acid in combination with β-alanine, glucose, xylitol, or proline (at a molar ratio of 1:1), and a variable amount of water, were used to extract the flavonoid aglycones: baicalein (1), scutellarein (3), wogonin (5), and oroxylin A (7), and their glycosides, baicalin (2), scutellarin (4), wogonoside (6) and oroxyloside (8) from the powdered bark of S. baicalensis. The chemical profile and yield of the extracts were determined using HPTLC and HPLC. The extractability of individual flavonoids was found to be influenced by the concentration of water (20–60%, w/w) in the NADES. Among the tested flavonoids, the extraction yield of baicalein (1), scutellarein (3), wogonin (5), oroxylin A (7) with NADES was 2 to 6 times that of aqueous methanol. However, the amount of their corresponding glycosides (baicalin (2), wogonoside (6) and oroxyloside (8)) extracted with NADES was only 1.5–1.8 times higher than with aqueous methanol. Interestingly, the more hydrophilic glycosides were less extracted than their corresponding aglycones despite the high hydrophilicity of the NADES. These results prove that NADES may be used for extraction of compounds with a wide range of hydrophilicity.

Immune evasion is now recognized as a key feature of cancer progression. In animal models, the activity of cytotoxic lymphocytes is suppressed in the tumour microenvironment by the immunosuppressive cytokine, Transforming Growth Factor (TGF)-β. Release from TGF-β-mediated inhibition restores anti-tumour immunity, suggesting a therapeutic strategy for human cancer. We demonstrate that human natural killer (NK) cells are inhibited in a TGF-β dependent manner following chronic contact-dependent interactions with tumour cells in vitro. In vivo, NK cell inhibition was localised to the human tumour microenvironment and primary ovarian tumours conferred TGF-β dependent inhibition upon autologous NK cells ex vivo. TGF-β antagonized the interleukin (IL)-15 induced proliferation and gene expression associated with NK cell activation, inhibiting the expression of both NK cell activation receptor molecules and components of the cytotoxic apparatus. Interleukin-15 also promotes NK cell survival and IL-15 excluded the pro-apoptotic transcription factor FOXO3 from the nucleus. However, this IL-15 mediated pathway was unaffected by TGF-β treatment, allowing NK cell survival. This suggested that NK cells in the tumour microenvironment might have their activity restored by TGF-β blockade and both anti-TGF-β antibodies and a small molecule inhibitor of TGF-β signalling restored the effector function of NK cells inhibited by autologous tumour cells. Thus, TGF-β blunts NK cell activation within the human tumour microenvironment but this evasion mechanism can be therapeutically targeted, boosting anti-tumour immunity.

International postgraduate students enrich higher education institutions and host societies, contributing economically, socially, and culturally. However, much less is known about how to improve their academic outcomes compared with their undergraduate counterparts. This study explores the impact of a non-traditional form of learning, a six-week immersive block model underpinned by guided, active learning pedagogy, on the academic success, satisfaction, and experiences of international postgraduate students at an Australian university. A convergent mix-methods design was used. Chi square tests and generalised estimating equations were used to compare the students’ success rates (N = 14,340) and unit satisfaction (N = 4903) in traditional semester and immersive block learning over five years. Qualitative insights were gathered via student focus groups (N = 9). Significant positive changes in success were observed after controlling for gender, age, discipline, and home region, with particularly strong positive effects for male and information technology students. Despite some challenges with depth of learning and placement organisation, focus group participants valued the clear timelines and flexible delivery, reporting that this supported effective time management and study-work–life-balance. Immersive block learning appears to be an effective strategy for transforming the experiences and outcomes of international postgraduate students in higher education.

Significance As well as having potent cytotoxic activity, natural killer (NK) cells have a regulatory role and interactions between NK cells and dendritic cells (DCs) aid DC maturation and adaptive immunity. However, the mechanisms underpinning NK–DC cross-talk are poorly defined. We show that tumor cells induce rapid production of the cytokine TNF superfamily member 14 (TNFSF14) in human NK cells and that these NK cells induce DC maturation in a TNFSF14-dependent manner. The synergistic activity of NK cell activation receptors in licensed NK cells couples the release of cytotoxic granules to TNFSF14 production. Thus, NK cell activation by tumor cells is linked to the initiation of adaptive immunity via TNFSF14-mediated NK–DC cross-talk. Interactions between natural killer (NK) cells and dendritic cells (DCs) aid DC maturation and promote T-cell responses. Here, we have analyzed the response of human NK cells to tumor cells, and we identify a pathway by which NK–DC interactions occur. Gene expression profiling of tumor-responsive NK cells identified the very rapid induction of TNF superfamily member 14 [TNFSF14; also known as homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes (LIGHT)], a cytokine implicated in the enhancement of antitumor responses. TNFSF14 protein expression was induced by three primary mechanisms of NK cell activation, namely, via the engagement of CD16, by the synergistic activity of multiple target cell-sensing NK-cell activation receptors, and by the cytokines IL-2 and IL-15. For antitumor responses, TNFSF14 was preferentially produced by the licensed NK-cell population, defined by the expression of inhibitory receptors specific for self-MHC class I molecules. In contrast, IL-2 and IL-15 treatment induced TNFSF14 production by both licensed and unlicensed NK cells, reflecting the ability of proinflammatory conditions to override the licensing mechanism. Importantly, both tumor- and cytokine-activated NK cells induced DC maturation in a TNFSF14-dependent manner. The coupling of TNFSF14 production to tumor-sensing NK-cell activation receptors links the tumor immune surveillance function of NK cells to DC maturation and adaptive immunity. Furthermore, regulation by NK cell licensing helps to safeguard against TNFSF14 production in response to healthy tissues.

In recent years, chronic degenerative diseases such as certain types of cancers, are becoming an evident issue. DNA damage has been for long recognized as a causal factor for cancer development because mutations or chromosomal aberrations affect oncogenes and tumor suppressor genes leading cells to malignant transformation and to the subsequent cancerous growth. Medicinal plants are often used for the prevention or treatment of various diseases with great scientific interest. Among the medicinal plants distributed in the Mediterranean region, Fraxinus angustifolia Vahl. has been used in traditional medicine for its remarkable curative properties. However, in spite of this popularity, little works have been performed on the activity so that further studies should be performed to investigate in depth the antimutagenic, antigenotoxic and antiproliferative activities of the plant. Thus, the present study was aimed to the evaluation of the potential antimutagenic, antigenotoxic and antiproliferative properties of leaves and stem bark extracts of this well-known tree. Antimutagenic activity was evaluated by Salmonella mutagenicity assay in Salmonella typhimurium TA98 and TA100 strains. The antigenotoxic potential was assessed by umu test in the strain of S. typhimurium TA1535/pSK1002. Antiproliferative activity was studied on human hepatoblastoma (HepG-2) and on breast adenocarcinoma (MCF-7) cell lines by MTT assay. Furthermore, the antiproliferative activity observed on cancer cells was compared with that on the human normal-like fibroblasts (TelCOFS02MA) and the selectivity index was calculated to understand if extracts were able to exert selective toxicity towards cancer cells. Moreover, phenolic compounds are plant substances with a large spectrum of biochemical activities with antioxidant, antimutagenic and anticarcinogenic effects. Based on the strong evidence of biological activities of phenolic compounds, the study was focused on the determination of total phenolics and flavonoids contents, and the phytochemical composition of the extracts assessed by LC/MS. The ethanol extracts of both leaves and stem barks showed significant from moderate to strong antimutagenic and antigenotoxic effects. In addition, selective cytotoxicity towards cancer cells was shown by ethanolic leaves extract and aqueous/chloroform leaves and stem bark extracts. The latter showed high levels of total phenolic contents among all the other extracts. Identified phenylethanoids (calceolariosides, verbascoside) and secoiridoids (oleuropein and ligstroside) could be responsible for the demonstrated broad spectrum of healthy properties.

COVID-19 vaccine breakthrough infection surveillance helps monitor trends in disease incidence and severe outcomes in fully vaccinated persons, including the impact of the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19. Reported COVID-19 cases, hospitalizations, and deaths occurring among persons aged ≥18 years during April 4-July 17, 2021, were analyzed by vaccination status across 13 U.S. jurisdictions that routinely linked case surveillance and immunization registry data. Averaged weekly, age-standardized incidence rate ratios (IRRs) for cases among persons who were not fully vaccinated compared with those among fully vaccinated persons decreased from 11.1 (95% confidence interval [CI] = 7.8-15.8) to 4.6 (95% CI = 2.5-8.5) between two periods when prevalence of the Delta variant was lower (<50% of sequenced isolates; April 4-June 19) and higher (≥50%; June 20-July 17), and IRRs for hospitalizations and deaths decreased between the same two periods, from 13.3 (95% CI = 11.3-15.6) to 10.4 (95% CI = 8.1-13.3) and from 16.6 (95% CI = 13.5-20.4) to 11.3 (95% CI = 9.1-13.9). Findings were consistent with a potential decline in vaccine protection against confirmed SARS-CoV-2 infection and continued strong protection against COVID-19-associated hospitalization and death. Getting vaccinated protects against severe illness from COVID-19, including the Delta variant, and monitoring COVID-19 incidence by vaccination status might provide early signals of changes in vaccine-related protection that can be confirmed through well-controlled vaccine effectiveness (VE) studies.COVID-19 vaccine breakthrough infection surveillance helps monitor trends in disease incidence and severe outcomes in fully vaccinated persons, including the impact of the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19. Reported COVID-19 cases, hospitalizations, and deaths occurring among persons aged ≥18 years during April 4-July 17, 2021, were analyzed by vaccination status across 13 U.S. jurisdictions that routinely linked case surveillance and immunization registry data. Averaged weekly, age-standardized incidence rate ratios (IRRs) for cases among persons who were not fully vaccinated compared with those among fully vaccinated persons decreased from 11.1 (95% confidence interval [CI] = 7.8-15.8) to 4.6 (95% CI = 2.5-8.5) between two periods when prevalence of the Delta variant was lower (<50% of sequenced isolates; April 4-June 19) and higher (≥50%; June 20-July 17), and IRRs for hospitalizations and deaths decreased between the same two periods, from 13.3 (95% CI = 11.3-15.6) to 10.4 (95% CI = 8.1-13.3) and from 16.6 (95% CI = 13.5-20.4) to 11.3 (95% CI = 9.1-13.9). Findings were consistent with a potential decline in vaccine protection against confirmed SARS-CoV-2 infection and continued strong protection against COVID-19-associated hospitalization and death. Getting vaccinated protects against severe illness from COVID-19, including the Delta variant, and monitoring COVID-19 incidence by vaccination status might provide early signals of changes in vaccine-related protection that can be confirmed through well-controlled vaccine effectiveness (VE) studies.

Preventing transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), in institutes of higher education presents a unique set of challenges because of the presence of congregate living settings and difficulty limiting socialization and group gatherings. Before August 2020, minimal data were available regarding COVID-19 outbreaks in these settings. On August 3, 2020, university A in North Carolina broadly opened campus for the first time since transitioning to primarily remote learning in March. Consistent with CDC guidance at that time (1,2), steps were taken to prevent the spread of SARS-CoV-2 on campus. During August 3-25, 670 laboratory-confirmed cases of COVID-19 were identified; 96% were among patients aged <22 years. Eighteen clusters of five or more epidemiologically linked cases within 14 days of one another were reported; 30% of cases were linked to a cluster. Student gatherings and congregate living settings, both on and off campus, likely contributed to the rapid spread of COVID-19 within the university community. On August 19, all university A classes transitioned to online, and additional mitigation efforts were implemented. At this point, 334 university A-associated COVID-19 cases had been reported to the local health department. The rapid increase in cases within 2 weeks of opening campus suggests that robust measures are needed to reduce transmission at institutes of higher education, including efforts to increase consistent use of masks, reduce the density of on-campus housing, increase testing for SARS-CoV-2, and discourage student gatherings.

Numerous aquatic invertebrates survive harsh environments by displaying dormancy as encysted embryos. This study aimed at determining whether metabolomics could provide molecular insight to explain the “dormancy syndrome” by highlighting functional pathways and metabolites, hence offering a novel comprehensive molecular view of dormancy. We compared the metabolome of morphologically distinct dormant encysted embryos (resting eggs) and non-dormant embryos (amictic eggs) of a rotifer ( Brachionus plicatilis ). Metabolome profiling revealed ~5,000 features, 1,079 of which were annotated. Most of the features were represented at significantly higher levels in non-dormant than dormant embryos. A large number of features was assigned to putative functional pathways indicating novel differences between dormant and non-dormant states. These include features associated with glycolysis, the TCA and urea cycles, amino acid, purine and pyrimidine metabolism. Interestingly, ATP, nucleobases, cyclic nucleotides, thymidine and uracil, were not detected in dormant resting eggs, suggesting an impairment of response to environmental and internal cues, cessation of DNA synthesis, transcription and plausibly translation in the dormant embryos. The levels of trehalose or its analogues, with a role in survival under desiccation conditions, were higher in resting eggs. In conclusion, the current study highlights metabolomics as a major analytical tool to functionally compare dormancy across species.

Gating the ion-permeation pathway in K + channels requires conformational changes in activation and inactivation gates. Here we have investigated the structural alterations associated with pH-dependent inactivation gating of the KcsA-Kv1.3 K + channel using solid-state NMR spectroscopy in direct reference to electrophysiological and pharmacological experiments. Transition of the KcsA-Kv1.3 K + channel from a closed state at pH 7.5 to an inactivated state at pH 4.0 revealed distinct structural changes within the pore, correlated with activation-gate opening and inactivation-gate closing. In the inactivated K + channel, the selectivity filter adopts a nonconductive structure that was also induced by binding of a pore-blocking tetraphenylporphyrin derivative. The results establish a structural link between inactivation and block of a K + channel in a membrane setting.

Work-integrated learning (WIL) continues to be a central element of higher education and may provide students with opportunities for both personal and professional development. However, the personal development opportunities afforded by WIL are often overshadowed by the more typical focus of work readiness. Increasing attention to self-authorship, an important stage of personal development when students start to make use of their internal voice to guide their beliefs, identity and relationships, could address this imbalance in WIL programs. This article explores the extent to which WIL enables self-authorship development in tourism management students. An interpretive, longitudinal case study methodology guided the study. The findings indicate the significant potential of WIL to foster students' self-authorship development given the opportunities and challenges inherent in placements. The Work-Integrated Learning for Self- authorship Development (WILSAD) model is proposed as a conceptual framework to assist WIL program designers in fostering self-authorship development in their students. [Author abstract]