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A mathematical framework of HIV and TB co-infection dynamics
Younger Dryas drought and IPO climate modulation during the Antarctic Cold Reversal in New Zealand
Linking sequence restoration capability of shuffled coronary angiography to coronary artery disease diagnosis
Comparative single-nucleus RNA-seq analysis revealed localized and cell type-specific pathways governing root-microbiome interactions
Abstract Roots can recognize and differentially respond to beneficial and pathogenic microbes, which are fundamental for maintaining root microbiome homeostasis, plasticity, and plant fitness. Meanwhile, roots are highly heterogeneous tissues with complex cell-type compositions and spatially distinct developmental stages. We found that beneficial microbe specifically induces the expression of translation-related genes in the proximal meristem cells, and diverse ribosome proteins and translation regulators are necessary for beneficial microbe-mediated growth promotion. Notably, the root maturation zone can still mount localized immune responses to root pathogens, including genes related to camalexin and triterpene biosynthesis. A triterpene biosynthesis mutant blocked the microbiome reshaping process upon GMI1000 infection. Our results indicate roots may have specialized immune responses in the maturation zone, and provide important insights and vital resources for further elucidating regulators of root-microbe interactions and microbiome reshaping.
The interaction between ΔNp63α and TAp63α, mediated by miR-205-5p, inhibits the migration of lung adenocarcinoma cells
Abstract Lung cancer is a highly lethal disease worldwide, resulting from a combination of genetic, epigenetic, and environmental factors. The amplification of specific chromosomal regions is a hallmark of cancer progression; for instance, the 3q region of chromosome 3 is notably amplified in lung cancer, contributing to early tumor development. TP63, a member of the p53 family, is located in the 3q region. The presence of two distinct sets of TP63 isoforms (ΔNp63 and TAp63) complicates its functional role. Furthermore, miR-205-5p, a crucial player in cancer progression, has a predicted target site in the 5’-untranslated region (5’-UTR) of TAp63 transcripts. To investigate a potential correlation between miR-205-5p and the ΔNp63 and TAp63 isoforms, we conducted an in silico study followed by experimental validations on clinical tissue samples. We found a significant positive correlation between the expression of miR-205-5p and both isoforms of TP63 in lung adenocarcinoma (LUAD) datasets. The correlation between ΔNp63 and miR-205-5p was further confirmed in tissue samples from LUAD patients. Subsequently, we overexpressed ΔNp63α in lung adenocarcinoma cell lines and observed an upregulation of miR-205-5p, TAp63α, and DICER in the A549 cell line. Overexpression of ΔNp63α also inhibited the migration of A549 cells by reducing epithelial-mesenchymal transition (EMT) markers and increasing mesenchymal-epithelial transition (MET) markers. We conducted a luciferase assay to investigate the direct interaction between miR-205-5p and the 5’-UTR of TAp63 and observed a positive association. Overexpression of miR-205-5p in the A549 cell line led to the upregulation of TAp63α and DICER. Additionally, we found a reduction in migration following miR-205-5p transfection. Based on these results, it appears that there is a ΔNp63α/miR-205-5p/TAp63α/DICER axis involved in the regulation of migration in lung adenocarcinoma, which is cell-specific.
Designer cannabinoids could be the key to pain relief without adverse effects
Emergence of an oceanic CO2 uptake hole under global warming
Evolution of airblast induced by roof collapse based on LBM-DEM
Abstract Airblast is a common safety hazard in block caving. It occurs when the roof of a goaf collapses suddenly over a large area, causing rapid compression and release of air, resulting in high-speed airflow that can cause injury and equipment damage. To effectively assess and prevent airblast hazards, it is necessary to study the catastrophic behavior of airblast parameters. The air gap, caving scale, and muckpile height are airblast key parameters. This research employs the LBM-DEM (Coupled Lattice Boltzmann Method and Discrete Element Method) to model the airblast formation process. Combined simulation experiments were conducted to examine the effects of air gap, muckpile height, and caving scale, with sensitivity analysis performed to determine airblast response. We propose a multivariate regression model that, using three arguments, expresses the maximum airblast velocity at the drawpoints. Results show that maximum air velocity during roof collapse is positively correlated with air gap and caving scale, and negatively correlated with muckpile height. At a caving scale of 103 m3, the air gap is the most critical parameter affecting maximum air velocity. Moreover, the interactions among these parameters exhibit distinct coupling characteristics. The findings provide a theoretical basis and reference for assessing and preventing airblast hazards.
Cholangiocarcinoma PDHA1 succinylation suppresses macrophage antigen presentation via alpha-ketoglutaric acid accumulation
BcatrB mediates pyrimethanil resistance in Botrytis cinerea revealed by transcriptomics analysis
Author Correction: “Pink power”—the importance of coralline algal beds in the oceanic carbon cycle
A reduction in energy costs induces integrated states of brain dynamics
Author Correction: Marine biogenic humic substances control iron biogeochemistry across the Southern Ocean
The evolution of the 2022–2024 eruption at Home Reef, Tonga, analyzed from space shows vent migration due to erosion
Abstract On September 9, 2022, a new eruption period began at the submarine volcano Home Reef, part of the Tonga Volcanic Arc. We integrated multi-sensor/multi-platform satellite datasets, including very high spatial resolution TerraSAR-X radar and PlanetScope multispectral data, together with Sentinel-2 and Landsat-8/9 as well as MODIS and VIIRS thermal data to monitor and characterize this latest eruption at Home Reef over a two-year period. Here, we present the results from this multi-sensor approach, used to investigate eruption dynamics (thermal activity and relative intensity level) and delineate changes in the shape and area of the newly formed island. The eruption showed four distinct phases: During September–October 2022, lava flows formed a ~ 54,900 m² circular island. In the following three eruption phases, the island grew towards the south (September–November 2023) and east (January 2024 and June–September 2024), expanding the island’s area to over 122,000 m². During each subsequent phase, the eruptive vent migrated toward the side of the island where the most erosion had occurred since the previous phase. This has implications for volcanic and tsunami hazards from island-forming eruptions of this type.
‘Anxiety is palpable’: detention of researchers at US border spurs travel worries
A cryptic pocket in CB1 drives peripheral and functional selectivity
Intrapleural pressure-controlled piezo-catalytic nanozyme for the inhibition of malignant pleural effusion
Synergistic activity of tafasitamab and metronomic chemotherapy on diffuse large B-cell lymphoma through inhibition of the AKT/mTOR signaling pathway
Abstract Tafasitamab is a novel humanized anti-CD19 monoclonal antibody, designed for the treatment of B-cell malignancies. Our study aims to enhance the direct, non-immune-mediated, activity of tafasitamab (TAFA) with the combination of metronomic chemotherapy (mCHEMO), including vinorelbine (mVNR) and etoposide (mETO), in preclinical models of diffuse large B-cell lymphoma (DLBCL). In vitro, the 144 h exposure of thrice-weekly mVNR, daily mETO, and single-dose TAFA significantly inhibited the viability of human CD19+ DLBCL cell lines (i.e., Toledo, OCI-LY3, and SU-DHL10) in a concentration-dependent manner. In all cell lines, the concomitant treatment with TAFA and mVNR or mETO showed a marked synergism, except for TAFA + mETO on SU-DHL10 cells. The TAFA + mCHEMO treatments promoted apoptosis, and the TAFA + mVNR combination significantly inhibited, already after 24 h, the phosphorylation of GSK3α/β, mTOR, p70S6K, RPS6, and TSC2 proteins in DLBCL cells. TAFA significantly increased the VNR and ETO intracellular concentrations in all DLBCL cells after 24 h, except for ETO levels in SU-DHL10. The TAFA + mCHEMO treatment strongly reduced the ABCB1, ABCG2, and c-MYC gene expression in SU-DHL10 cells. In vivo, the TAFA + mVNR combination was well tolerated, significantly reduced the volumes of subcutaneous DLBCL masses, and increased the overall survival of mice affected by systemic DLBCL. We report additional mechanisms to enhance the direct activity of TAFA with mCHEMO synergistically in DLBCL cells in vitro and in vivo, suggesting the use of this combination schedule into future clinical trials.
Sulphostin-inspired N-phosphonopiperidones as selective covalent DPP8 and DPP9 inhibitors
Abstract Covalent chemical probes and drugs combine unique pharmacologic properties with the availability of straightforward compound profiling technologies via chemoproteomic platforms. These advantages have fostered the development of suitable electrophilic “warheads” for systematic covalent chemical probe discovery. Despite undisputable advances in the last years, the targeted development of proteome-wide selective covalent probes remains a challenge for dipeptidyl peptidase (DPP) 8 and 9 (DPP8/9), intracellular serine hydrolases of the pharmacologically relevant dipeptidyl peptidase 4 activity/structure homologues (DASH) family. Here, we show the exploration of the natural product Sulphostin, a DPP4 inhibitor, as a starting point for DPP8/9 inhibitor development. The generation of Sulphostin-inspired N-phosphonopiperidones leads to derivatives with improved DPP8/9 inhibitory potency, an enhanced proteome-wide selectivity and confirmed DPP8/9 engagement in cells, thereby representing that structural fine-tuning of the warhead’s leaving group may represent a straightforward strategy for achieving target selectivity in exoproteases such as DPPs.