Electrical impedance tomography (EIT), a noninvasive and radiation-free medical imaging technique, has been used for continuous real-time regional lung aeration. However, adhesive electrodes could ...cause discomfort and increase the risk of skin injury during prolonged measurement. Additionally, the conductive gel between the electrodes and skin could evaporate in long-term usage and deteriorate the signal quality. To address these issues, in this work, textile electrodes integrated with a clothing belt are proposed to achieve EIT lung imaging along with a custom portable EIT system. The simulation and experimental results have verified the validity of the proposed portable EIT system. Furthermore, the imaging results of using the proposed textile electrodes were compared with commercial electrocardiogram electrodes to evaluate their performance.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Arsenic (As) contamination in a paddy environment can cause phytotoxicity and elevated As accumulation in rice (Oryza sativa). The mechanism of As detoxification in rice is still poorly understood.
...We isolated an arsenate (As(V))-sensitive mutant of rice. Genomic resequencing and complementation identified OsCLT1, encoding a CRT-like transporter, as the causal gene for the mutant phenotype.
OsCLT1 is localized to the envelope membrane of plastids. The glutathione and γ-glutamylcysteine contents in roots of Osclt1 and RNA interference lines were decreased markedly compared with the wild-type (WT). The concentrations of phytochelatin PC2 in Osclt1 roots were only 32% and 12% of that in WT after As(V) and As(III) treatments, respectively. OsCLT1 mutation resulted in lower As accumulation in roots but higher As accumulation in shoots when exposed to As(V). Under As(III) treatment, Osclt1 accumulated a lower As concentration in roots but similar As concentration in shoots to WT. Further analysis showed that the reduction of As(V) to As(III) was decreased in Osclt1. Osclt1 was also hypersensitive to cadmium (Cd).
These results indicate that OsCLT1 plays an important role in glutathione homeostasis, probably by mediating the export of γ-glutamylcysteine and glutathione from plastids to the cytoplasm, which in turn affects As and Cd detoxification in rice.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract This work develops a composite system of reduced graphene oxide (rGO)–iron oxide nanoparticles (rGO–IONP) that can synergistically induce physical and chemical damage to ...methicillin-resistant Staphylococcus aureus (MRSA) that are present in subcutaneous abscesses. rGO–IONP was synthesized by the chemical deposition of Fe 2 + /Fe 3 + ions on nanosheets of rGO in aqueous ammonia. The antibacterial efficacy of the as-prepared rGO–IONP was evaluated in a mouse model with MRSA-infected subcutaneous abscesses. Upon exposure to a near-infrared laser in vitro , rGO–IONP synergistically generated localized heat and large amounts of hydroxyl radicals, which inactivated MRSA. The in vivo results reveal that combined treatment with localized heat and oxidative stress that is caused by hydroxyl radicals accelerated the healing of wounds associated with MRSA-infected abscesses. The above results demonstrate that an rGO–IONP nanocomposite system that can effectively inactivate multiple-drug-resistant bacteria in subcutaneous infections was successfully developed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Autophagy is an evolutionarily conserved pathway to degrade damaged proteins and organelles for subsequent recycling in cells during times of nutrient deprivation. This process plays an important ...role in tumor development and progression, allowing cancer cells to survive in nutrient-poor environments. The plant kingdom provides a powerful source for new drug development to treat cancer. Several plant extracts induce autophagy in cancer cells. However, little is known about the role of plant extracts in autophagy inhibition, particularly autophagy-related (ATG) proteins. In this study, we employed S-tagged gamma-aminobutyric acid receptor associated protein like 2 (GABARAPL2) as a reporter to screen 48 plant extracts for their effects on the activity of autophagy protease ATG4B. Xanthium strumarium and Tribulus terrestris fruit extracts were validated as potential ATG4B inhibitors by another reporter substrate MAP1LC3B-PLA
. The inhibitory effects of the extracts on cellular ATG4B and autophagic flux were further confirmed. Moreover, the plant extracts significantly reduced colorectal cancer cell viability and sensitized cancer cells to starvation conditions. The fruit extract of X. strumarium consistently diminished cancer cell migration and invasion. Taken together, the results showed that the fruit of X. strumarium may have an active ingredient to inhibit ATG4B and suppress the proliferation and metastatic characteristics of colorectal cancer cells.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Triple-negative breast cancer (TNBC) remains an unmet medical challenge. We investigated metabolic dysregulation in TNBCs by using our multi-omics database (n = 465, the largest to date). TNBC ...samples were classified into three heterogeneous metabolic-pathway-based subtypes (MPSs) with distinct metabolic features: MPS1, the lipogenic subtype with upregulated lipid metabolism; MPS2, the glycolytic subtype with upregulated carbohydrate and nucleotide metabolism; and MPS3, the mixed subtype with partial pathway dysregulation. These subtypes were validated by metabolomic profiling of 72 samples. These three subtypes had distinct prognoses, molecular subtype distributions, and genomic alterations. Moreover, MPS1 TNBCs were more sensitive to metabolic inhibitors targeting fatty acid synthesis, whereas MPS2 TNBCs showed higher sensitivity to inhibitors targeting glycolysis. Importantly, inhibition of lactate dehydrogenase could enhance tumor response to anti-PD-1 immunotherapy in MPS2 TNBCs. Collectively, our analysis demonstrated the metabolic heterogeneity of TNBCs and enabled the development of personalized therapies targeting unique tumor metabolic profiles.
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•The metabolic reprogramming and heterogeneity of TNBC is systematically characterized•TNBCs are classified into three subtypes on the basis of metabolic pathways•Three subtypes show distinct sensitivities to various metabolic inhibitors•Inhibition of LDH enhances tumor response to anti-PD-1 immunotherapy in MPS2 TNBCs
Gong et al. reveal the metabolic heterogeneity of triple-negative breast cancer and identify three metabolic-pathway-based subtypes with distinct molecular features and sensitivities to various metabolic inhibitors. They find that inhibition of lactate dehydrogenase could enhance the anti-PD-1 immunotherapy response in a certain subtype of triple-negative breast cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Calvarial bone healing remains difficult but may be improved by stimulating chondrogenesis of implanted stem cells. To simultaneously promote chondrogenesis and repress adipogenesis of stem cells, we ...built a CRISPRai system that comprised inactive Cas9 (dCas9), two fusion proteins as activation/repression complexes and two single guide RNA (sgRNA) as scaffolds for recruiting activator (sgRNAa) or inhibitor (sgRNAi). By plasmid transfection and co-expression in CHO cells, we validated that dCas9 coordinated with sgRNAa to recruit the activator for mCherry activation and also orchestrated with sgRNAi to recruit the repressor for d2EGFP inhibition, without cross interference. After changing the sgRNA sequence to target endogenous Sox9/PPAR-γ, we packaged the entire CRISPRai system into an all-in-one baculovirus for efficient delivery into rat bone marrow-derived mesenchymal stem cells (rBMSC) and verified simultaneous Sox9 activation and PPAR-γ repression. The activation/inhibition effects were further enhanced/prolonged by using the Cre/loxP-based hybrid baculovirus. The CRISPRai system delivered by the hybrid baculovirus stimulated chondrogenesis and repressed adipogenesis of rBMSC in 2D culture and promoted the formation of engineered cartilage in 3D culture. Importantly, implantation of the rBMSC engineered by the CRISPRai improved calvarial bone healing. This study paves a new avenue to translate the CRISPRai technology to regenerative medicine.
Abstract
Many collective phenomena such as epidemic spreading and cascading failures in socioeconomic systems on networks are caused by perturbations of the dynamics. How perturbations propagate ...through networks, impact and disrupt their functions may depend on the network, the type and location of the perturbation as well as the spreading dynamics. Previous work has analyzed the retardation effects of the nodes along the propagation paths, suggesting a few transient propagation "scaling” regimes as a function of the nodes’ degree, but regardless of motifs such as triangles. Yet, empirical networks consist of motifs enabling the proper functioning of the system. Here, we show that basic motifs along the propagation path jointly determine the previously proposed scaling regimes of distance-limited propagation and degree-limited propagation, or even cease their existence. Our results suggest a radical departure from these scaling regimes and provide a deeper understanding of the interplay of self-dynamics, interaction dynamics, and topological properties.
Collagens are the most abundant proteins in extra cellular matrix and important components of tumor microenvironment. Recent studies have showed that aberrant expression of collagens can influence ...tumor cell behaviors. However, their roles in hepatocellular carcinoma (HCC) are poorly understood.
In this study, we screened all 44 collagen members in HCC using whole transcriptome sequencing data from the public datasets, and collagen type IV alpha1 chain (COL4A1) was identified as most significantly differential expressed gene. Expression of COL4A1 was detected in HCC samples by quantitative real-time polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry (IHC). Finally, functions and potential mechanisms of COL4A1 were explored in HCC progression.
COL4A1 is the most significantly overexpressed collagen gene in HCC. Upregulation of COL4A1 facilitates the proliferation, migration and invasion of HCC cells through FAK-Src signaling. Expression of COL4A1 is upregulated by RUNX1 in HCC. HCC cells with high COL4A1 expression are sensitive to the treatment with FAK or Src inhibitor.
COL4A1 facilitates growth and metastasis in HCC via activation of FAK-Src signaling. High level of COL4A1 may be a potential biomarker for diagnosis and treatment with FAK or Src inhibitor for HCC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Inflammatory bowel disease (IBD) is a global health concern with varying levels and trends across countries and regions. Understanding these differences is crucial for effective prevention and ...treatment strategies.
Using data from the 2019 Global Burden of Disease study, we examine IBD incidence, mortality, and disability-adjusted life years (DALYs) rates in 198 countries from 1990 to 2019. To assess changes in the burden of IBD, estimated annual percentage changes (EAPC) were calculated, and a Bayesian age-period-cohort model was used to predict the future 30-year trends of IBD.
In 2019, there were 405,000 new IBD cases globally (95% uncertainty interval (UI) 361,000 to 457,000), with 41,000 deaths (95% UI 35,000 to 45,000) and 1.62million DALYs (95% UI 1.36-1.92million). The global age-standardized incidence rate in 2019 was 4.97 per 100,000 person-years (95% UI 4.43 to 5.59), with a mortality rate of 0.54 (95% UI 0.46 to 0.59) and DALYs rate of 20.15 (95% UI 16.86 to 23.71). From 1990 to 2019, EAPC values for incidence, mortality, and DALYs rates were - 0.60 (95% UI - 0.73 to - 0.48), - 0.69 (95% UI - 0.81 to - 0.57), and - 1.04 (95% UI - 1.06 to - 1.01), respectively. Overall, the burden of IBD has shown a slow decline in recent years. In SDI stratification, regions with higher initial SDI (high-income North America and Central Europe) witnessed decreasing incidence and mortality rates with increasing SDI, while regions with lower initial SDI (South Asia, Oceania, and Latin America) experienced a rapid rise in incidence but a decrease in mortality with increasing SDI. Predictions using a Bayesian model showed lower new cases and deaths from 2020 to 2050 than reference values, while the slope of the predicted incidence-time curve closely paralleled that of the 2019 data.
Increasing cases, deaths, and DALYs highlight the sustained burden of IBD on public health. Developed countries have stabilized or declining incidence rates but face high prevalence and societal burden. Emerging and developing countries experience rising incidence. Understanding these changes aids policymakers in effectively addressing IBD challenges in different regions and economic contexts.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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