Aberrant regulation of suprabasin (SBSN) is associated with the development of cancer and immune disorders. SBSN influences tumor cell migration, proliferation, angiogenesis, and immune resistance. ...In this study, we investigated the potential correlation between
expression and immune infiltration in thyroid cancer.
The expression of SBSN in 80 papillary thyroid carcinoma (PTC) specimens was determined using quantitative reverse-transcription polymerase chain reaction, western blotting, and immunohistochemical staining. The expression of SBSN in 9 cases of poorly differentiated thyroid carcinoma (PDTC) and 18 cases of anaplastic thyroid carcinoma (ATC) was evaluated by immunohistochemical staining. Comprehensive bioinformatics analysis of
expression was performed using The
Genome Atlas and Gene Expression Omnibus datasets, and the relationship of SBSN expression with M2 macrophages and T regulatory cells (Tregs) in ATC and PTC was verified by immunohistochemical staining.
Compared with those in adjacent normal tissues, the expression levels of SBSN mRNA and protein were significantly higher in PTC tissues. SBSN expression level was correlated with that of cervical lymph node metastasis in PTC patients. Immunohistochemical staining results showed statistically significant differences among high-positive expression rates of SBSN in PTC, PDTC, and ATC. Functional enrichment analysis showed that
expression was associated with pathways related to cancer, cell signaling, and immune response. Furthermore, analysis of the tumor microenvironment (using CIBERSORT-ABS and xCell algorithms) showed that
expression affected immune cell infiltration and the cancer immunity cycle, and immunohistochemistry confirmed a significant increase in M2 macrophage and Treg infiltration in tumor tissues with high-positive SBSN expression.
These findings reveal that SBSN may be involved in thyroid carcinogenesis, tumor dedifferentiation progression, and immunosuppression as an important regulator of tumor immune cell infiltration.
Plasmid conjugation plays an important role in the dissemination of antibiotic-resistance genes. The emergence of multidrug-resistant isolates of
poses grave challenges in treating infections caused ...by this notorious nosocomial pathogen. Yet, the composition, functionality, and regulation of conjugative machinery utilized by
remain poorly understood. Here, we found that conjugation of the major plasmid pAB3 of
is mediated by a type IVB secretion system similar to the Dot/Icm transporter of
. Furthermore, the expression of the structural genes of the Dot/Icm-like system is co-regulated with genes involved in central metabolism by the GacS/GacA two-component system in response to various metabolites, including intermediates of the tricarboxylic acid cycle. Loss of GacS/A also severely impaired bacterial virulence. These results establish that
coordinates metabolism with plasmid conjugation and virulence by sensing nutrient availability, which may be exploited to develop inhibitory agents for controlling the spread of drug-resistance genes and virulence factors. IMPORTANCE Plasmid conjugation is known to be an energy-expensive process, but our understanding of the molecular linkage between conjugation and metabolism is limited. Our finding reveals that
utilizes a two-component system to co-regulate metabolism, plasmid transfer, and virulence by sensing reaction intermediates of key metabolic pathways, which suggests that nutrient availability dictates not only bacterial proliferation but also horizontal gene transfer. The identification of Dot/Icm-like proteins as components of a conjugation system involved in the dissemination of antibiotic-resistance genes by
has provided important targets for the development of agents capable of inhibiting virulence and the spread of anti-microbial-resistance genes in bacterial communities.
The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) is a complex ecosystem that drives tumor progression; however, in-depth single cell characterization of the PDAC TME and ...its role in response to therapy is lacking. Here, we perform single-cell RNA sequencing on freshly collected human PDAC samples either before or after chemotherapy. Overall, we find a heterogeneous mixture of basal and classical cancer cell subtypes, along with distinct cancer-associated fibroblast and macrophage subpopulations. Strikingly, classical and basal-like cancer cells exhibit similar transcriptional responses to chemotherapy and do not demonstrate a shift towards a basal-like transcriptional program among treated samples. We observe decreased ligand-receptor interactions in treated samples, particularly between TIGIT on CD8 + T cells and its receptor on cancer cells, and identify TIGIT as the major inhibitory checkpoint molecule of CD8 + T cells. Our results suggest that chemotherapy profoundly impacts the PDAC TME and may promote resistance to immunotherapy.
Background
The bacterial communities of the root surface and rhizosphere play a crucial role in the decomposition and transformation of soil nitrogen (N) and are also affected by soil N levels and ...distribution, especially the composition and diversity, which are sensitive to changes in the environment with high spatial and temporal heterogeneity of ammonium N (NH
4
+
-N) and nitrate N (NO
3
-
-N).
Methods
One-year-old seedlings of
Cunninghamia lanceolata
and
Schima superba
were subjected to N stress (0.5 mmol L
-1
) and normal N supply (2 mmol L
-1
), and five different N form ratios (NH
4
+
-N to NO
3
-
-N ratio of 10:0, 0:10, 8:2, 2:8, and 5:5) were created. We analyze the changes in composition and diversity of bacteria in the root surface and rhizosphere of two tree species by high-throughput sequencing.
Results
Differences in the composition of the major bacteria in the root surface and rhizosphere of
C.lanceolata
and
S. superba
under N stress and N form ratios were not significant. The dominant bacterial phyla shared by two tree species included Proteobacteria and Bacteroidota. Compared to normal N supply, the patterns of diversity in the root surface and rhizosphere of two tree species under N stress were distinct for each at five N form ratios. Under N stress, the bacterial diversity in the root surface was highest at NH
4
+
-N to NO
3
-
-N ratio of 10:0 of
C. lanceolata
, whereas in the root surface, it was highest at the NH
4
+
-N to NO
3
-
-N ratio of 0:10 of
S. superba
. The NH
4
+
-N to NO
3
-
-N ratio of 5:5 reduced the bacterial diversity in the rhizosphere of two tree species, and the stability of the bacterial community in the rhizosphere was decreased in
C. lanceolata
. In addition, the bacterial diversity in the root surface was higher than in the rhizosphere under the N stress of two tree species.
Conclusion
The bacterial compositions were relatively conserved, but abundance and diversity changed in the root surface and rhizosphere of
C. lanceolata
and
S. superba
under N stress and different N form ratios. The heterogeneity of ammonium and nitrate N addition should be considered for N-stressed environments to improve bacterial diversity in the rhizosphere of two tree species.
Background/Aims: Pterostilbene (Pts), a natural dimethylated analog of resveratrol from blueberries, exerts antioxidative and anti-apoptotic effects in various diseases. This study aims to ...investigate the protective effects and mechanism of Pts against acetaminophen (APAP)-induced hepatotoxicity in vivo. Methods: C57BL/6 mice were treated with APAP or APAP+Pts. HepG2 cells were used to further explore the underlying mechanisms in vitro. The effects of Pts on hepatotoxicity were measured by commercial kits, Hematoxylin and Eosin (H&E) straining, TUNEL assay, Western blot analysis, and Flow cytometry assay. Results: In vivo, Pts treatment effectively protected against APAP-induced severe liver injury by decreasing the lethality rate, the serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, liver histological injury, liver malondialdehyde (MDA) formation and myeloperoxidase (MPO) levels and by increasing liver glutathione (GSH) and superoxide dismutase (SOD) levels. Moreover, in Pts-treated mice, the nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway was activated; however, APAP-induced c-Jun NH2-terminal kinase (JNK) activation, mitochondrial Bcl-2 Associated X Protein (Bax) translocation, apoptosis-inducing factor (AIF) levels and cytochrome c release were attenuated. In vitro, Pts was found to reverse hydrogen peroxide (H2O2) -induced cytotoxicity, reactive oxygen species (ROS) production and apoptosis that depended on Nrf2 activation. Moreover, Pts induced a dose-dependent increase in the phosphorylation of AMP-activated protein kinase (AMPK), serine/threonine kinase (Akt), and glycogen synthase kinase 3β (GSK3β) in HepG2 cells. Moreover, Pts protect against APAP or H2O2-induced toxicity were effectively attenuated or abolished in HepG2 Nrf2-/- cells and Nrf2-/- mice. Conclusion: Our data suggest that Pts protects against APAP-induced toxicity by activating Nrf2 via the AMPK/Akt/GSK3β pathway.
The coupling of light absorbers to cocatalysts with well-designed optical and catalytic properties is of fundamental importance for the development of efficient photoelectrocatalytic devices for ...solar-driven water splitting. We achieved an effective loading of visible-light-active porous hybrid photoanodes for water photooxidation with ultrasmall (∼1–2 nm), highly disordered CoO(OH) x nanoparticles using a two-step impregnation method. Under visible light (λ > 420 nm) irradiation, the resulting photoanodes significantly outperformed photoanodes loaded with conventional cobalt-based cocatalyst (Co-Pi) comprising larger nanoparticles (∼5 nm) in terms of both Faradaic efficiency of oxygen evolution (by the factor of 2) and performance stability under long-term irradiation. A combination of STEM, XAS, cyclic voltammetry, and photoelectrochemical techniques was used to elucidate the advantages of using ultrasmall CoO(OH) x nanoparticles as cocatalysts. Specifically, due to the high transparency of ultrasmall CoO(OH) x nanoparticles in the visible range, higher loading of porous photoanodes with cobalt catalytic sites can be achieved, while the photocurrent losses due to parasitic light absorption by the cocatalyst are minimized. Notably, a significant enhancement in stability of ultrasmall CoO(OH) x nanoparticles in borate electrolytes as compared to phosphate electrolytes has been observed. EXAFS data recorded before and after photoelectrocatalysis indicated that the effect of the electrolyte on the stability can be explained by the difference in structural ordering dictated by different interaction of the electrolyte anions with cobalt ions, as corroborated by DFT calculations. This study highlights the strong impact of structural and optical properties of cocatalysts as well as the strong influence of the electrolyte composition on the activity and stability of photoelectrocatalytic systems comprising transition metal oxide electrocatalysts.
Big Data Analytics in Healthcare Systems Wang, Lidong; Alexander, Cheryl Ann
International journal of mathematical, engineering and management sciences,
02/2019, Letnik:
4, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Big Data analytics can improve patient outcomes, advance and personalize care, improve provider relationships with patients, and reduce medical spending. This paper introduces healthcare data, big ...data in healthcare systems, and applications and advantages of Big Data analytics in healthcare. We also present the technological progress of big data in healthcare, such as cloud computing and stream processing. Challenges of Big Data analytics in healthcare systems are also discussed.
Ubiquitination is a posttranslational modification of proteins that significantly affects protein stability and function. The specificity of substrate recognition is determined by ubiquitin E3 ligase ...during ubiquitination. Human Deltex (DTX) protein family, which functions as ubiquitin E3 ligases, comprises five members, namely, DTX1, DTX2, DTX3, DTX3L, and DTX4. The characteristics and functional diversity of the DTX family proteins have attracted significant attention over the last decade. DTX proteins have several physiological and pathological roles and are closely associated with cell signal transduction, growth, differentiation, and apoptosis, as well as the occurrence and development of various tumors. Although they have been extensively studied in various species, data on structural features, biological functions, and potential mechanisms of action of the DTX family proteins remain limited. In this review, recent research progress on each member of the DTX family is summarized, providing insights into future research directions and potential strategies in disease diagnosis and therapy.
The Mongolian gazelle (Procapra gutturosa) population has shown a considerable range of contractions and local extinctions over the last century, owing to habitat fragmentation and poaching. A ...thorough understanding of the genetic diversity and structure of Mongolian gazelle populations in fragmented habitats is critical for planning effective conservation strategies. In this study, we used eight microsatellite loci and mitochondrial cytochrome b (Cytb) to compare the levels of genetic diversity and genetic structure of Mongolian gazelle populations in the Hulun Lake National Nature Reserve (HLH) with those in the China-Mongolia border area (BJ). The results showed that the nucleotide diversity and observed heterozygosity of the HLH population were lower than those of the BJ population. Moreover, the HLH and BJ populations showed genetic differentiation. We concluded that the HLH population had lower genetic diversity and a distinct genetic structure compared with the BJ population. The genetic diversity of fragmented Mongolian gazelle populations, can be improved by protecting these populations while reinforcing their gene exchange with other populations. For example, attempts can be made to introduce new individuals with higher genetic diversity from other populations to reduce inbreeding.
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