Temporally resolved proteomics identifies nidogen-2 as a cotarget in pancreatic cancer that modulates fibrosis and therapy response.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by increasing fibrosis, which can enhance tumor progression and spread. Here, we undertook an unbiased temporal assessment of the matrisome of the highly metastatic KPC (Pdx1-Cre, LSL-KrasG12D/+, LSL-Trp53R172H/+) and poorly metastatic KPflC (Pdx1-Cre, LSL-KrasG12D/+, Trp53fl/+) genetically engineered mouse models of pancreatic cancer using mass spectrometry proteomics. Our assessment at early-, mid-, and late-stage disease reveals an increased abundance of nidogen-2 (NID2) in the KPC model compared to KPflC, with further validation showing that NID2 is primarily expressed by cancer-associated fibroblasts (CAFs). Using biomechanical assessments, second harmonic generation imaging, and birefringence analysis, we show that NID2 reduction by CRISPR interference (CRISPRi) in CAFs reduces stiffness and matrix remodeling in three-dimensional models, leading to impaired cancer cell invasion. Intravital imaging revealed improved vascular patency in live NID2-depleted tumors, with enhanced response to gemcitabine/Abraxane. In orthotopic models, NID2 CRISPRi tumors had less liver metastasis and increased survival, highlighting NID2 as a potential PDAC cotarget.

Microplastic emissions from household washing machines: preliminary findings from Greater Kuala Lumpur (Malaysia).

Microplastics have been recognized as emerging pollutants with potential ecotoxicological impact. The contribution of washing machine use to microplastics emission at the household level is still not completely understood. This study aims to characterize microplastic emissions in laundry water from household washing machines from Greater Kuala Lumpur (Malaysia). Microplastics were found between 6.9E-3 and 0.183 g/m3 in laundry water at household level. Microplastic shapes of fiber and fragment consist of polyester, nylon, and acrylic with average length of 2258.59 µm and were also identified in these laundry water samples. Questionnaire survey findings demonstrated fabric properties and washing parameters both likely contribute to microplastic emissions in laundry water and, ultimately, wastewater treatment plant influent. The impact of fabric properties and washing parameter factors on microplastic emission in laundry water at the household level merits further investigation. The findings of this study demonstrated the potential of laundry water as a microplastic source at the household level within a developing country.

Health care equity and access for marginalised young people: a longitudinal qualitative study exploring health system navigation in Australia.

BACKGROUND: Young people have unique social, emotional and developmental needs that require a welcoming and responsive health system, and policies that support their access to health care. Those who are socially or culturally marginalised may face additional challenges in navigating health care, contributing to health inequity. The aim of this study was to understand health system navigation, including the role of technology, for young people belonging to one or more marginalised groups, in order to inform youth health policy in New South Wales, Australia. METHODS: This qualitative longitudinal study involved 2-4 interviews each over 6 to 12 months with marginalised young people aged 12-24 years living in NSW. The analysis used Nvivo software and grounded theory. RESULTS: We interviewed 41 young people at baseline who were living in rural or remote areas, sexuality and/or gender diverse, refugee, homeless, and/or Aboriginal. A retention rate of over 85% was achieved. Nineteen belonged to more than one marginalised group allowing an exploration of intersectionality. General practitioners (family physicians) were the most commonly accessed service throughout the study period. Participants were ambivalent about their healthcare journeys. Qualitative analysis identified five themes: 1. Technology brings opportunities to understand, connect and engage with services 2. Healthcare journeys are shaped by decisions weighing up convenience, engagement, effectiveness and affordability. 3. Marginalised young people perceive and experience multiple forms of discrimination leading to forgone care. 4. Multiple marginalisation makes health system navigation more challenging 5. The impact of health system complexity and fragmentation may be mitigated by system knowledge and navigation support CONCLUSIONS: The compounding effects of multiple discrimination and access barriers were experienced more strongly for young people belonging to mutiple marginalised groups. We identify several areas for improving clinical practice and policy. Integrating technology and social media into processes that facilitate access and navigation, providing respectful and welcoming services that recognise diversity, improving health literacy and involving professionals in advocacy and navigation support may help to address these issues.

Changes in physicochemical properties of corn starch upon modifications by atmospheric pressure plasma jet.

The influences of atmospheric pressure plasma jet on different physicochemical properties of corn starch were evaluated after treated with the plasma jet (30 min) at different strengths (400 W-800 W). Our results demonstrated that residual aging effects of plasma on starch could be eliminated by washing the treated samples with distilled water at a ratio of 1:30, w/v. After plasma and washing treatments, significant (p < 0.05) reductions in pasting properties including peak viscosity, final viscosity, and setback of starch samples (up to -87.1%, -92.0%, and -93.3%, respectively) were observed with increasing plasma intensity. Apparently, plasma jet could increase the solubility and paste clarity of starch sample. Surface morphological characterization illustrated that plasma etching resulted in some physical changes on starch granules. Modifications in these physicochemical properties of corn starch by employing the plasma jet treatment might be useful in food applications requiring starch ingredients of low viscosity and high paste clarity.

Investigation of the relationship between prostate cancer and MSMB and NCOA4 genetic variants and protein expression.

Two genome-wide association studies (GWAS) identified the ß-microseminoprotein (MSMB) promoter SNP, rs10993994:C>T, as significantly associated with prostate cancer (PC) risk. Follow-up studies demonstrate that the variant allele directly affects expression of the MSMB-encoded protein, PSP94, and also suggest that it affects mRNA expression levels of an adjacent gene, NCOA4, which is involved in androgen receptor transactivation. In a population-based study of 1,323 cases and 1,268 age-matched controls, we found the NCOA4 SNP, rs7350420:T>C, was associated with a 15% reduction in PC risk, but the association was not significant after adjustment for the rs10993994:C>T genotype. Tumor tissue microarrays of 519 radical prostatectomy patients were used to measure PSP94 and NCOA4 protein expression. Taken together, these data confirm that the rs10993994:C>T variant allele is associated with decreased PSP94 expression, and the association is stronger in tumor compared to normal prostate tissue. No association was observed between rs10993994:C>T and NCOA4 expression, and only moderate associations were seen between two NCOA4 SNPs, rs10761618:T>C and rs7085433:G>A, and NCOA4 protein expression. These data indicate that the increase in PC risk associated with rs10993994:C>T is likely mediated by the variant's effect on PSP94 expression; however, this effect does not extend to NCOA4 in the data presented here.