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Platinum-based chemotherapy, including cisplatin, carboplatin, and oxaliplatin, is prescribed to 10-20% of all cancer patients. Unfortunately, platinum resistance develops in a significant number of patients and is a determinant of clinical outcome. Extensive research has been conducted to understand and overcome platinum resistance, and mechanisms of resistance can be categorized into several broad biological processes, including (1) regulation of drug entry, exit, accumulation, sequestration, and detoxification, (2) enhanced repair and tolerance of platinum-induced DNA damage, (3) alterations in cell survival pathways, (4) alterations in pleiotropic processes and pathways, and (5) changes in the tumor microenvironment. As a resource to the cancer research community, we provide a comprehensive overview accompanied by a manually curated database of the >900 genes/proteins that have been associated with platinum resistance over the last 30 years of literature. The database is annotated with possible pathways through which the curated genes are related to platinum resistance, types of evidence, and hyperlinks to literature sources. The searchable, downloadable database is available online at http://ptrc-ddr.cptac-data-view.org .

The relationship between taxation and welfare regime in Taiwan has largely been unexplored to date. This study argues that since taxation capacity of the state decides the fate of new welfare programs such as the public provision of long-term care, it also affects the trajectory of the welfare regime. Through the analysis of Taiwan's tax revenue structure and tax base, this study reveals that Taiwan, unlike many new democracies, has shone away from relying on goods and services taxes but at the same time continues to provide preferential tax treatment for the corporate world. The result has been the erosion of tax base which makes introducing new welfare programs extremely difficult even when new policies allow for credit-claiming. Therefore, the familialistic welfare regime persists because of a weakened taxation capacity. Furthermore, the political determinants of the weakened taxation capacity can be found in identity-based party politics, an influential capital vs acquiescent labor and the limited bargaining power of civil society.

Traffic sign detection, as a critical branch of object detection, plays an essential role in both assisted driving and autonomous driving technologies. In this paper, we propose MASG-Net, a lightweight detection network designed to improve the accuracy and efficiency of traffic sign detection. First, we introduce a channel attention mechanism into MobileNetV3 to create a novel E-block structure and design E-mobilenet, a lightweight backbone network, to replace the backbone in YOLOv4-tiny, significantly enhancing feature extraction while reducing parameters. Second, we propose a multi-scale dilated convolution spatial pyramid pooling (MDSPP) module to expand the receptive field of feature maps, enabling the network to capture multi-scale contextual information effectively. Finally, a semantic information guidance (SIG) module is introduced to leverage deep semantic information to guide shallow feature layers, improving the detection of small traffic signs and enhancing robustness against cluttered backgrounds. Experimental results on the CCTSDB, GTSDB and TT100K datasets demonstrate that MASG-Net achieves superior detection performance, particularly for small and challenging traffic signs, while maintaining high efficiency with an inference speed of 203.6 FPS. These results highlight MASG-Net’s potential for real-time traffic sign detection in practical applications.

FLT3 mutations are prevalent in AML patients and confer poor prognosis. Crenolanib, a potent type I pan-FLT3 inhibitor, is effective against both internal tandem duplications and resistance-conferring tyrosine kinase domain mutations. While crenolanib monotherapy has demonstrated clinical benefit in heavily pretreated relapsed/refractory AML patients, responses are transient and relapse eventually occurs. Here, to investigate the mechanisms of crenolanib resistance, we perform whole exome sequencing of AML patient samples before and after crenolanib treatment. Unlike other FLT3 inhibitors, crenolanib does not induce FLT3 secondary mutations, and mutations of the FLT3 gatekeeper residue are infrequent. Instead, mutations of NRAS and IDH2 arise, mostly as FLT3 -independent subclones, while TET2 and IDH1 predominantly co-occur with FLT3 -mutant clones and are enriched in crenolanib poor-responders. The remaining patients exhibit post-crenolanib expansion of mutations associated with epigenetic regulators, transcription factors, and cohesion factors, suggesting diverse genetic/epigenetic mechanisms of crenolanib resistance. Drug combinations in experimental models restore crenolanib sensitivity. FLT3 is commonly mutated in acute myeloid leukaemia and treatment with FLT3 inhibitors often ends with relapse. Here, the authors perform exome sequencing of samples from patients treated with the FLT3 inhibitor, crenolanib, to show that resistance occurs due to diverse molecular mechanisms, not primarily due to secondary FLT3 mutations.

Anthocyanins are flavonoid-derived metabolites that contribute to plant and human health. At present, few studies have studied the biosynthesis and accumulation mechanism of anthocyanins in pepper leaves. The role of CaMYBA–CaMYC–CaTTG1 complex in anthocyanin biosynthesis in pepper leaves was studied. Yeast two-hybrid and dual-luciferase experiments showed that CaMYBA, CaMYC, and CaTTG1 could form an MYB–bHLH–WD40 (MBW) complex. They also have transcriptional activation on the anthocyanin synthesis structural genes CaCHS , CaCHI , CaF3H , CaF3′5′H , CaANS , CaDFR , and CaUFGT . Silencing CaMYBA or CaMYC could decrease the content of anthocyanin in pepper leaves. Transient overexpression of CaMYBA in tobacco indicated that CaMYBA determines the function of an MBW complex. Further analysis showed that CaMYBA could activate the expression of CaMYC by binding to its promoter. Overall, our study expands the understanding of the regulatory mechanism of anthocyanin synthesis in pepper leaves and has important significance for creating more pepper plants with different color patterns by gene editing engineering.

Group B Streptococcus (GBS) rectovaginally colonizes up to 20% of women worldwide and is a leading cause of invasive infections during pregnancy, contributing annually to a significant proportion of preterm births, neonatal infections, and stillbirths. Despite its reputation as a perinatal pathogen, GBS infection rates in non-pregnant adults are also increasing. While much progress has been made to understand transcriptional regulation of virulence by two-component systems, many aspects of GBS virulence regulation remain understudied. Although many bacterial pathogens utilize high temperature response A (HtrA) family serine proteases to regulate virulence and stress responses through varied mechanisms, the function of HtrA in GBS was unknown. Here, we demonstrate that HtrA is localized to the GBS membrane and regulates the abundance of endogenous surface and secreted proteins, including a subset of virulence factors. Although deletion of htrA (Δ htrA ) increased dissemination to placentas and fetuses, this strain caused significantly fewer adverse pregnancy outcomes compared to isogenic wild-type (WT). Placentas from Δ htrA -infected dams contained more chemokines, pro-inflammatory IL-1β, and neutrophil myeloperoxidase than isogenic WT-infected placentas, suggesting that Δ htrA GBS induces potent neutrophil chemotaxis. However, immunosuppressive IL-10 was present at increased concentration, which may in part explain the attenuation of adverse pregnancy outcomes during Δ htrA infection. Finally, we note that recombinant GBS HtrA directly cleaves human fibronectin in vitro , highlighting that this protease may also target host substrates during infection. Together, these findings support a role for HtrA as a post-translational regulator of GBS virulence and suggest that inhibiting HtrA activity may hold therapeutic promise against GBS induced adverse pregnancy outcomes.

Prioritizing candidate biomarkers for verification remains a formidable obstacle to the translation of protein diagnostics to clinical applications. Whiteaker et al . assemble a multistage, targeted proteomics pipeline to relieve this bottleneck and use a mouse cancer model to demonstrate its analytical performance. High-throughput technologies can now identify hundreds of candidate protein biomarkers for any disease with relative ease. However, because there are no assays for the majority of proteins and de novo immunoassay development is prohibitively expensive, few candidate biomarkers are tested in clinical studies. We tested whether the analytical performance of a biomarker identification pipeline based on targeted mass spectrometry would be sufficient for data-dependent prioritization of candidate biomarkers, de novo development of assays and multiplexed biomarker verification. We used a data-dependent triage process to prioritize a subset of putative plasma biomarkers from >1,000 candidates previously identified using a mouse model of breast cancer. Eighty-eight novel quantitative assays based on selected reaction monitoring mass spectrometry were developed, multiplexed and evaluated in 80 plasma samples. Thirty-six proteins were verified as being elevated in the plasma of tumor-bearing animals. The analytical performance of this pipeline suggests that it should support the use of an analogous approach with human samples.

This Analysis reports the development and assessment of 645 multiple reaction monitoring (MRM) mass spectrometry assays to quantify 319 targeted human breast cancer proteins. The results of this pilot project coordinated among three individual groups suggest that an organized international effort to generate MRM assays to the human proteome will be possible. Multiple reaction monitoring (MRM) mass spectrometry has been successfully applied to monitor targeted proteins in biological specimens, raising the possibility that assays could be configured to measure all human proteins. We report the results of a pilot study designed to test the feasibility of a large-scale, international effort for MRM assay generation. We have configured, validated across three laboratories and made publicly available as a resource to the community 645 novel MRM assays representing 319 proteins expressed in human breast cancer. Assays were multiplexed in groups of >150 peptides and deployed to quantify endogenous analytes in a panel of breast cancer–related cell lines. The median assay precision was 5.4%, with high interlaboratory correlation ( R 2 > 0.96). Peptide measurements in breast cancer cell lines were able to discriminate among molecular subtypes and identify genome-driven changes in the cancer proteome. These results establish the feasibility of a large-scale effort to develop an MRM assay resource.

Background Alzheimer's disease (AD) and other forms of dementia are the seventh leading cause of death. Studies discern the inclusion of air pollution among modifiable risk factors for dementia, while limited studies are for China. This study aims to examine the short-term association between airborne particulate matter (PM) and the hospitalizations of AD, including the economic costs in China. Methods A total of 4975 cases of AD patients hospitalized from 2017 to 2019, were collected from nine city and 411 medical institutions in Sichuan Province, China. Data on air pollutants such as PM 2.5 , PM 10 , and NO 2 were obtained from 183 air quality monitoring stations in Sichuan Province. A time series-generalized additive model was used to estimate the association between short-term exposure to PM (lag1–lag7 and moving average lag01–lag07) and AD hospital admissions (HAs), stratified by gender, age, and season. Results Positive short-term exposure to airborne PM was found for the HAs of AD. The greatest effect on the number of AD inpatients was on single-day lag1 (PM 2.5 :1.034 (95% confidence interval (CI) 1.011, 1.058)). The association was also significant in the two-pollutant model. In the study period, 16.48% of AD HAs were attributed to the effect of PM. The total economic costs of AD attributable to PM exposure were US$ 2.56 million, including US$ 2.25 million of direct medical costs and US$ 0.31 million of indirect economic costs. Conclusions This study suggests that short-term exposure to airborne PM may increase the risk of AD HAs in Sichuan Province and result in associated economic costs.

Pseudomonas aeruginosa is found in 48%–52% of chronic wound biofilms, where its resistance to antimicrobials and host immunity presents a major clinical challenge. Although hypochlorous acid (HOCl) is known to be an effective antimicrobial, its mechanism of action remains unclear because standard experimental conditions often produce a mixture of HOCl and hypochlorite (OCl⁻), making it difficult to isolate the effects of HOCl. Here, we use proteomic profiling to investigate the effects of a pure, stable HOCl gel on P. aeruginosa biofilms in a physiologically relevant chronic wound model. We applied HOCl gel (5.7 mM, pH 6) to mature P. aeruginosa biofilms established in a wound‐mimicking flow model. Proteins were analyzed using tandem mass tag (TMT)‐based quantitative proteomics, identifying 1,878 proteins. HOCl treatment significantly reduced biofilm viability and altered the abundance of 330 proteins. We observed substantial depletion of proteins involved in biosynthesis, virulence, antibiotic resistance, and biofilm formation, alongside enrichment of stress response proteins. These findings indicate a shift toward survival phenotypes and weakened pathogenicity. Our data reveal that HOCl disrupts multiple pathways essential for P. aeruginosa survival and virulence. Crucially, our experimental design eliminates confounding factors that can lead to unintentional testing of mixed HOCl and OCl⁻ species, allowing us to assess the specific effects of HOCl. These findings call for a re‐evaluation of HOCl research methodologies and reiterate the importance of realistic infection models in antimicrobial testing. Impact statement: We tested a gel containing a pure, stable form of hypochlorous acid (HOCl) against P. aeruginosa. To ensure our results reflect the true effects of HOCl we used a host‐relevant biofilm model. The HOCl gel disrupted bacterial metabolism, impacted proteins associated with virulence, and changed the abundance antibiotic resistance proteins. These findings suggest the gel could improve healing in chronic wound infections and reduce antibiotic use.