Viral hepatitis is a global health concern mostly caused by hepatitis B virus (HBV) and hepatitis C virus (HCV). The late diagnosis and delayed treatment of HBV and HCV infections can cause ...irreversible liver damage and the occurrence of cirrhosis and hepatocellular carcinoma. Detecting the presence and activity of HBV and HCV is the cornerstone of the diagnosis and management of related diseases. However, the traditional method shows limitations. The utilization of nanomaterials has been of great significance in the advancement of virus detection technologies due to their unique mechanical, electrical, and optical properties. Here, we categorized and illustrated the novel approaches used for the diagnosis of HBV and HCV.
Empagliflozin has been reported to protect endothelial cell function, regardless of diabetes status. However, the role of empagliflozin in microvascular protection during myocardial ischemia ...reperfusion injury (I/R) has not been fully understood.
Electron microscopy, western blots, immunofluorescence, qPCR, mutant plasmid transfection, co-immunoprecipitation were employed to explore whether empagliflozin could alleviate microvascular damage and endothelial injury during cardiac I/R injury.
In mice, empagliflozin attenuated I/R injury-induced microvascular occlusion and microthrombus formation. In human coronary artery endothelial cells, I/R injury led to adhesive factor upregulation, endothelial nitric oxide synthase inactivation, focal adhesion kinase downregulation, barrier dysfunction, cytoskeletal degradation and cellular apoptosis; however, empagliflozin treatment diminished these effects. Empagliflozin improved mitochondrial oxidative stress, mitochondrial respiration and adenosine triphosphate metabolism in I/R-treated human coronary artery endothelial cells by preventing the phosphorylation of dynamin-related protein 1 (Drp1) and mitochondrial fission 1 protein (Fis1), thus repressing mitochondrial fission. The protective effects of empagliflozin on mitochondrial homeostasis and endothelial function were abrogated by the re-introduction of phosphorylated Fis1, but not phosphorylated Drp1, suggesting that Fis1 dephosphorylation is the predominant mechanism whereby empagliflozin inhibits mitochondrial fission during I/R injury. Besides, I/R injury induced Fis1 phosphorylation primarily by activating the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) pathway, while empagliflozin inactivated this pathway by exerting anti-oxidative effects.
These results demonstrated that empagliflozin can protect the microvasculature by inhibiting the DNA-PKcs/Fis1/mitochondrial fission pathway during myocardial I/R injury.
Diabetic kidney disease (DKD) is the most common complication of diabetes mellitus and a leading cause of kidney failure worldwide. Despite its prevalence, the mechanisms underlying early kidney ...damage in DKD remain poorly understood. In this study, we used single nucleus RNA-seq to construct gene regulatory networks (GRNs) in the kidney cortex of patients with early DKD. By comparing these networks with those of healthy controls, we identify cell type-specific changes in genetic regulation associated with diabetic status. The regulon activities of FXR (NR1H4) and CREB5 were found to be upregulated in kidney proximal convoluted tubule epithelial cells (PCTs), which were validated using immunofluorescence staining in kidney biopsies from DKD patients. In vitro experiments using cultured HK2 cells showed that FXR and CREB5 protected cells from apoptosis and epithelial-mesenchymal transition. Our findings suggest that FXR and CREB5 may be promising targets for early intervention in patients with DKD.
Atrial fibrillation (AF) is one of the most prevalent sustained arrhythmias, however, epidemiological data may understate its actual prevalence. Meanwhile, AF is considered to be a major cause of ...ischemic strokes due to irregular heart-rhythm, coexisting chronic vascular inflammation, and renal insufficiency, and blood stasis. We studied co-expressed genes to understand relationships between atrial fibrillation (AF) and stroke and reveal potential biomarkers and therapeutic targets of AF-related stroke.
AF-and stroke-related differentially expressed genes (DEGs) were identified via bioinformatic analysis Gene Expression Omnibus (GEO) datasets GSE79768 and GSE58294, respectively. Subsequently, extensive target prediction and network analyses methods were used to assess protein-protein interaction (PPI) networks, Gene Ontology (GO) terms and pathway enrichment for DEGs, and co-expressed DEGs coupled with corresponding predicted miRNAs involved in AF and stroke were assessed as well.
We identified 489, 265, 518, and 592 DEGs in left atrial specimens and cardioembolic stroke blood samples at < 3, 5, and 24 h, respectively. LRRK2, CALM1, CXCR4, TLR4, CTNNB1, and CXCR2 may be implicated in AF and the hub-genes of CD19, FGF9, SOX9, GNGT1, and NOG may be associated with stroke. Finally, co-expressed DEGs of ZNF566, PDZK1IP1, ZFHX3, and PITX2 coupled with corresponding predicted miRNAs, especially miR-27a-3p, miR-27b-3p, and miR-494-3p may be significantly associated with AF-related stroke.
AF and stroke are related and ZNF566, PDZK1IP1, ZFHX3, and PITX2 genes are significantly associated with novel biomarkers involved in AF-related stroke.
Chronic hepatitis B virus (HBV) infection is a worldwide public health threat that results in huge morbidity and mortality. Late diagnosis and delayed treatment of HBV infections can cause ...irreversible liver damages and occurrence of cirrhosis and hepatocellular carcinoma (HCC). Detection of the presence and activity of HBV are the cornerstones of diagnosis and management in HBV related disease. Moreover, comprehensive knowledge of the mechanisms regulating HBV immunobiology is pivotal for managing diseases related with HBV. Here we tried to categorize and illustrate the classical and novel approaches used for diagnosis of HBV. Also, we reviewed our current knowledge on the immunobiology of HBV related HCC.
With rapid increases in incidence, diverse subtypes, and complicated etiologies, kidney disease remains a global public health problem. Iron, as an essential trace element, has pleiotropic effects on ...renal function and the progression of kidney diseases. A two-sample Mendelian randomization (MR) analysis was implemented to determine the potential causal effects between systemic iron status on different kidney diseases. Systemic iron status was represented by four iron-related biomarkers: serum iron, ferritin, transferrin saturation (TfSat), and total iron binding capacity (TIBC). For systemic iron status, 163,511, 246,139, 131,471, and 135,430 individuals were included in the genome-wide association study (GWAS) of serum iron, ferritin, TfSat, and TIBC, respectively. For kidney diseases, 653,143 individuals (15,658 cases and 637,485 controls), 657,076 individuals (8160 cases and 648,916 controls), and 659,320 individuals (10,404 cases and 648,916 controls) were included for immunoglobulin A nephropathy (IgAN), acute kidney disease (AKD), and chronic kidney disease (CKD), respectively. Our MR results showed that increased serum iron odds ratio (OR): 1.10; 95% confidence interval (95% CI): 1.04, 1.16; p < 0.0042, ferritin (OR: 1.30; 95% CI: 1.14, 1.48; p < 0.0042), and TfSat (OR: 1.07; 95% CI: 1.04, 1.11; p < 0.0042) and decreased TIBC (OR: 0.92; 95% CI: 0.88, 0.97; p < 0.0042) were associated with elevated IgAN risk. However, no significant associations were found between systemic iron status and AKD or CKD. In our MR study, the genetic evidence supports elevated systemic iron status as a causal effect on IgAN, which suggests a potential protective effect of iron chelation on IgAN patients.
Accurate temperature distribution measurement during high-intensity focused ultrasound (HIFU) treatment is crucial for avoiding damage to sensitive tissues and organ systems. To surpass the ...constraints of conventional thermocouple temperature measurement approaches, near-infrared temperature measurement, as a non-invasive imaging method, is proposed. Using infrared glass as a temperature observation window allows for studying the temperature distribution on the surface of biological tissues under ultrasound exposure. The temperature rise in the tissues near the infrared glass under ultrasound exposure was investigated through numerical simulations. Moreover, the effects of the shear waves and thermal viscosity induced by the infrared glass were also analyzed. The results indicate that the shear wave in the glass weakens the intensity of the ultrasound pressure in the focal region while enhancing the efficiency of the acoustic thermal conversion. Thermal viscosity increases the acoustic pressure and temperature in the focal zone. Furthermore, oblique incidence facilitates the transformation of the acoustic thermal effect, caused by shear waves and thermal viscosity, resulting in an expanded temperature rise range on the tissue surface. The non-linear effects in the ultrasound field further enhance the acoustic thermal effect. Significant errors occur in the near-infrared method when utilizing infrared glass for temperature measurement, with the shear waves exerting the most substantial impact on the temperature distribution. These research findings carry substantial implications for optimizing treatment plans, enhancing treatment safety and efficacy, and offering potential application value for temperature control in HIFU treatment.
We performed a meta-analysis of the safety and efficacy of anticoagulation treatment for atrial fibrillation (AF) in relation to renal function. We also examined the change in estimated glomerular ...filtration rate (eGFR) from baseline and compared the outcomes for patients with stable and worsening renal function.
We selected studies that used randomized controlled trials in which outcomes for direct oral anticoagulants (DOACs) (dabigatran, rivaroxaban, apixaban, or edoxaban) were compared with those for warfarin in AF patients with normal, mild or moderate renal function, except the severe one (creatinine clearance<30).
We assessed five clinical trials, involving 72,608 patients. Pooled analysis indicated that the risk of stroke was lower for DOACs than for warfarin among patients with mild renal impairment (Risk ratio, 0.79; 95% confidence interval, 0.68–0.91) and moderate renal impairment (0.80, 0.69–0.92). No major differences were found in patients with normal renal function. Additionally, DOACs were associated with fewer major bleeds among patients with normal (0.77, 0.70–0.84), mild (0.86, 0.77–0.95), and moderate renal impairment (0.73, 0.65–0.82). Among those treated with DOACs, a lower dosage was associated with lower risk of major bleeding (0.75, 0.68–0.83) and higher risk of stroke or systemic embolism (1.28, 1.12–1.47). Further, DOACs tended to be associated with a lower estimated glomerular filtration rate (eGFR) than warfarin even after 30months. Finally, we found significant differences in the risk of stroke (2.09, 1.64–2.68) and major bleeding (2.01, 1.66–2.42) between patients with stable and worsening renal function.
DOACs have a greater clinical benefit than warfarin with respect to renal function. They are associated with a comparatively lower risk of stroke and major bleeding, as well lower eGFR. This suggests these agents are a better choice in patients with renal disease.
•DOACs have a greater clinical benefit than warfarin with respect to renal function.•Higher dosage DOAC might be associated with a lower risk of stroke or systemic embolism and a higher risk of major bleeding than lower dose DOACs with respect to renal dysfunction.•DOACs have a favorable risk in patients with renal function deteriorated.
To achieve efficient and environmental reuse of waste ribbons, artworks reconstructed from waste ribbons for decorative occasions were inspired by the dedicated and determined people working against ...coronavirus disease 2019 (COVID-19) and developed through a handmade and delicate strategy. With the theme of ‘Ordinary * Extraordinary,’ the artworks aim to convey endless positive energy and hope to people suffering from COVID-19. To fulfill the art reconstruction, the design idea, composition design and color design were comprehensively considered and carefully described. The artworks were applied for decoration in hospital wards and the home environment. Their composition and color gave medical workers, patients and ordinary people suffering from COVID-19 a sense of comfort and warmth. All positive energy from our artworks accompanied people and encouraged them never to give up and overcome COVID-19. The art reconstruction of waste ribbons proposed in this study may provide an excellent way for the reuse of waste ribbons. More importantly, it improves the added value of products and strengthens people's determination to overcome COVID-19.
Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colon, characterized by continuous mucosal inflammation. Recently, some studies have considered it as part of an ...inflammatory bowel disease-based global network. Herein, with the aim of identifying the underlying potential genetic mechanisms involved in the development of UC, multiple algorithms for weighted correlation network analysis (WGCNA), principal component analysis (PCA), and linear models for microarray data algorithm (LIMMA) were used to identify the hub genes. The map of platelet activation, ligand-receptor interaction, calcium signaling pathway, and cAMP signaling pathway showed significant links with UC development, and the hub genes
,
,
,
,
, and
, which are associated with immune dysregulation and tumorigenesis in biological function, were found by multiple powerful bioinformatics methods. Analysis of The Cancer Genome Atlas (TCGA) also showed that the low expression of
,
,
, and
may be correlated with a poor prognosis of overall survival (OS) in colorectal cancer (CRC) patients (all
< 0.05), while no significance detected in both of
and
. In addition, low expression of
,
,
,
, and
may be associated with a poor prognosis in recurrence free survival (RFS) time (all
< 0.05), but no significant difference was identified in
. Moreover, the
,
, and
with the highest enrichment score were detected as the master regulators of hub genes. In summary, these results indicated the central role of the hub genes of
,
,
,
,
, and
, in response to UC progression, as well as the development of UC to CRC, thus shedding light on the molecular mechanisms involved and assisting with drug target validation.