Bulk aluminum nitride (AlN) crystals with different polarities were grown by physical vapor transport (PVT). The structural, surface, and optical properties of m-plane and c-plane AlN crystals were ...comparatively studied by using high-resolution X-ray diffraction (HR-XRD), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. Temperature-dependent Raman measurements showed that the Raman shift and the full width at half maximum (FWHM) of the E
(high) phonon mode of the m-plane AlN crystal were larger than those of the c-plane AlN crystal, which would be correlated with the residual stress and defects in the AlN samples, respectively. Moreover, the phonon lifetime of the Raman-active modes largely decayed and its line width gradually broadened with the increase in temperature. The phonon lifetime of the Raman TO-phonon mode was changed less than that of the LO-phonon mode with temperature in the two crystals. It should be noted that the influence of inhomogeneous impurity phonon scattering on the phonon lifetime and the contribution to the Raman shift came from thermal expansion at a higher temperature. In addition, the trend of stress with increasing 1000/temperature was similar for the two AlN samples. As the temperature increased from 80 K to ~870 K, there was a temperature at which the biaxial stress of the samples transformed from compressive to tensile stress, while their certain temperature was different.
The global battle against the COVID-19 pandemic relies strongly on the human defense of antibody, which is assumed to bind the antigen’s receptor binding domain (RBD) with its hypervariable region ...(HVR). Due to the similarity to other viruses such as SARS, however, our understanding of the antibody-virus interaction has been largely limited to the genomic sequencing, which poses serious challenges to containment and rapid serum testing. Based on the physical/chemical nature of the interaction, infrared spectroscopy was employed to reveal the binding disparity, the real cause of the antibody-virus specificity at the molecular level, which is inconceivable to be investigated otherwise. Temperature dependence was discovered in the absorption value from the 1550 cm−1 absorption band, attributed to the hydrogen bonds by carboxyl/amino groups, binding the SARS-CoV-2 spike protein and closely resembled SARS-CoV-2 or SARS-CoV-1 antibodies. The infrared absorption intensity, associated with the number of hydrogen bonds, was found to increase sharply between 27 °C and 31 °C, with the relative absorbance matching the hydrogen bonding numbers of the two antibody types (19 vs. 12) at 37 °C. Meanwhile, the ratio of bonds at 27 °C, calculated by thermodynamic exponentials, produces at least 5% inaccuracy. Beyond genomic sequencing, the temperature dependence, as well as the bond number match at 37 °C between relative absorbance and the hydrogen bonding numbers of the two antibody types, is not only of clinical significance in particular but also as a sample for the physical/chemical understanding of vaccine–antibody interactions in general.
Aristolochic acid nephropathy (AAN) is a rapidly progressive interstitial nephropathy caused by Aristolochic acid (AA). AAN is associated with the development of nephropathy and urothelial carcinoma. ...It is estimated that more than 100 million people worldwide are at risk of developing AAN. However, the underlying mechanisms driving renal deterioration in AAN remain poorly understood, and the treatment options are limited.
We obtained GSE27168 and GSE136276 series matrix data from the Gene Expression Omnibus (GEO) related to AAN. Using the R Studio environment, we applied the limma package and WGCNA package to identify co-differently expressed genes (co-DEGs). By GO/KEGG/GSVA analysis, we revealed common biological pathways. Subsequently, co-DEGs were subjected to the String database to construct a protein-protein interaction (PPI) network. The MCC algorithms implemented in the Cytohubba plugin were employed to identify hub genes. The hub genes were cross-referenced with the transcription factor (TF) database to identify hub TFs. Immune infiltration analysis was performed to identify key immune cell groups by utilizing CIBERSORT. The expressions of AAN-associated hub TFs were verified in vivo and in vitro. Finally, siRNA intervention was performed on the two TFs to verify their regulatory effect in AAN.
Our analysis identified 88 co-DEGs through the "limma" and "WGCNA" R packages. A PPI network comprising 53 nodes and 34 edges was constructed with a confidence level >0.4. ATF3 and c-JUN were identified as hub TFs potentially linked to AAN. Additionally, expressions of ATF3 and c-JUN positively correlated with monocytes, basophils, and vessels, and negatively correlated with eosinophils and endothelial cells. We observed a significant increase in protein and mRNA levels of these two hub TFs. Furthermore, it was found that siRNA intervention targeting ATF3, but not c-JUN, alleviated cell damage induced by AA. The knockdown of ATF3 protects against oxidative stress and inflammation in the AAN cell model.
This study provides novel insights into the role of ATF3 in AAN. The comprehensive analysis sheds light on the molecular mechanisms and identifies potential biomarkers and drug targets for AAN treatment.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is considered a new biomarker for atherosclerosis, but its ability to predict cardiovascular outcomes has been controversial. This study aimed to ...address the lack of data on PCSK9, coronary heart disease (CHD) severity, and major cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM).
A total of 2984 T2DM patients underwent selective coronary angiography, and their serum PCSK9 levels were measured using enzyme-linked immunosorbent assay. Correlation and logistic regression analyses were performed to investigate the association between PCSK9 expression and CHD severity. This study used Cox regression analysis to assess the association between circulating PCSK9 levels and the risk of MACEs.
Circulating PCSK9 levels were significantly higher in the CHD group than in the non-CHD group 554.62 (265.11) ng/mL vs. 496.86 (129.05) ng/mL, p < 0.001. Circulating PCSK9 levels positively correlated with CHD severity (diseased vessels: r = 0.35, p < 0.001; Gensini score: r = 0.46, p < 0.001). Elevated PCSK9 levels are an independent risk factor for CHD risk and severity (CHD group vs. non-CHD group: OR = 2.829, 95% CI: 1.771-4.520, p < 0.001; three vessel disease group vs. one vessel disease group: OR = 4.800, 95% CI: 2.387-9.652, p < 0.001; high GS group vs. low GS group: OR = 5.534, 95% CI: 2.733-11.208, p < 0.001). Through a six-year follow-up and multivariate Cox regression analysis, elevated circulating PCSK9 levels were found to be independently associated with MACEs in all participants (HR: 3.416, 5% CI: 2.485-4.697, p < 0.001; adjusted HR: 2.780, 95% CI: 1.930-4.004, p < 0.001).
Serum PCSK9 levels were positively correlated with multi-vessel CHD and Gensini score. Elevated circulating PCSK9 levels are an independent risk factor for CHD and increased incidence of MACEs in T2DM.
Elevated lipoprotein(a) Lp(a) is a risk factor for coronary heart disease (CHD), but there are few studies on the prediction of future cardiovascular events by Lp(a) and its LPA single nucleotide ...polymorphisms (SNPs). The aim of this study was to investigate whether elevated Lp(a) and its SNPs can predict cardiovascular events. We evaluated whether Lp(a) and LPA SNPs rs6415084 and rs12194138 were associated with the incidence rate and severity of CHD. All participants were followed up for 5 years. Elevated Lp(a) is an independent risk factor for the risk and severity of CHD (CHD group vs. control group: OR = 1.793, 95% CI: 1.053-2.882, p = 0.043; multiple-vessel disease group vs. single-vessel disease group: OR = 1.941, 95% CI: 1.113-3.242, p = 0.027; high GS group vs. low GS group: OR = 2.641, 95% CI: 1.102-7.436, p = 0.040). Both LPA SNPs were risk factors for CHD, and were positively associated with the severity of CHD (LPA SNPs rs6415084: CHD group vs. control group: OR = 1.577, 95% CI: 1.105-1.989, p = 0.004; multiple-vessel disease group vs. single-vessel disease group: OR = 1.613, 95% CI: 1.076-2.641, p = 0.030; high GS group vs. low GS group: OR = 1.580, 95% CI: 1.088-2.429, p = 0.024; LPA SNPs rs12194138: CHD group vs. control group: OR = 1.475, 95% CI: 1.040-3.002, p = 0.035; multiple-vessel disease group vs. single-vessel disease group: OR = 2.274, 95% CI: 1.060-5.148, p = 0.038; high GS group vs. low GS group: OR = 2.067, 95% CI: 1.101-4.647, p = 0.021). After 5 years of follow-up, elevated Lp(a) and LPA SNPs rs6415084 and rs12194138 can independently predict cardiovascular events. The increase of serum Lp(a) and LPA SNPs rs6415084 and rs12194138 are associated with increased prevalence and severity of CHD, and can independently predict cardiovascular events.
Highlights • Stable drug binding in the channel pore inhibits the influenza A M2 channel. • Mutations in M2 perturb drug binding stability. • Structural biology and molecular simulations guide drug ...design for mutant M2 channels. • The M2 pore-binding site can bind to inhibitors of varying sizes.
Malignant tumor is a largely harmful disease worldwide. The cure rate of malignant tumors increases with the continuous discovery of anti-tumor drugs and the optimisation of chemotherapy options. ...However, drug resistance of tumor cells remains a massive obstacle in the treatment of anti-tumor drugs. The heterogeneity of malignant tumors makes studying it further difficult for us. In recent years, using single-cell sequencing technology to study and analyse circulating tumor cells can avoid the interference of tumor heterogeneity and provide a new perspective for us to understand tumor drug resistance.
Chemical synthesis is state-of-the-art, and, therefore, it is generally based on chemical intuition or experience of researchers. The upgraded paradigm that incorporates automation technology and ...machine learning (ML) algorithms has recently been merged into almost every subdiscipline of chemical science, from material discovery to catalyst/reaction design to synthetic route planning, which often takes the form of unmanned systems. The ML algorithms and their application scenarios in unmanned systems for chemical synthesis were presented. The prospects for strengthening the connection between reaction pathway exploration and the existing automatic reaction platform and solutions for improving autonomation through information extraction, robots, computer vision, and intelligent scheduling were proposed.
Rhododendron shanii W.P. Fang 1983 (Ericaceae) is woody plant naturally distributed in the southwest of Anhui, China. The complete chloroplast genome sequence of R. shanii was generated by ...whole-genome next-generation sequencing data and assembled based on three Rhododendron species chloroplast genome. The complete chloroplast genome sequence of R. shanii was 204,170 bp and divided into four distinct regions: small single-copy region (2615 bp), large single-copy region (107,189 bp), and a pair of inverted repeat regions (47,183 bp). The genome annotation displayed 150 genes, including 95 protein-coding genes, 47 tRNA genes, and eight rRNA genes. Phylogenetic analysis with the Ericaceae reported chloroplast genomes revealed that R. shanii is sister to the clade comprising R. delavayi, R. griersonianum and R. platypodum.
Robust activation of glial cells has been reported to occur particularly during the pathogenesis of bone cancer pain (BCP). Researchers from our group and others have shown that histone deacetylases ...(HDACs) play a significant role in modulating glia-mediated immune responses; however, it still remains unclear whether HDACs are involved in the activation of glial cells during the development of BCP.
BCP model was established by intra-tibia tumor cell inoculation (TCI). The expression levels and distribution sites of histone deacetylases (HDACs) in the spinal dorsal horn and dorsal root ganglia were evaluated by Western blot and immunofluorescent staining, respectively. Suberoylanilide hydroxamic acid (SAHA), a clinically used HDAC inhibitor, was then intraperitoneally and intrathecally injected to rescue the increased expression levels of HDAC1 and HDAC2. The analgesic effects of SAHA administration on BCP were then evaluated by measuring the paw withdrawal thresholds (PWTs). The effects of SAHA on activation of glial cells and expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) in the spinal dorsal horn and dorsal root ganglia of TCI rats were further evaluated by immunofluorescent staining and Western blot analysis. Subsequently, the effects of SAHA administration on tumor growth and cancer cell-induced bone destruction were analyzed by hematoxylin and eosin (HE) staining and micro-CT scanning.
TCI caused rapid and long-lasting increased expression of HDAC1/HDAC2 in glial cells of the spinal dorsal horn and dorsal root ganglia. Inhibiting HDACs by SAHA not only reversed TCI-induced upregulation of HDACs but also inhibited the activation of glial cells in the spinal dorsal horn and dorsal root ganglia, and relieved TCI-induced mechanical allodynia. Further, we found that SAHA administration could not prevent cancer infiltration or bone destruction in the tibia, which indicated that the analgesic effects of SAHA were not due to its anti-tumor effects. Moreover, we found that SAHA administration could inhibit GSK3β activity in the spinal dorsal horn and dorsal root ganglia, which might contributed to the relief of BCP.
Our findings suggest that HDAC1 and HDAC2 are involved in the glia-mediated neuroinflammation in the spinal dorsal horn and dorsal root ganglia underlying the pathogenesis of BCP, which indicated that inhibiting HDACs by SAHA might be a potential strategy for pain relief of BCP.
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