An association study of NRAMP1, VDR, MBL and their interaction with the susceptibility to tuberculosis in a Chinese population

SummaryObjectivesTo investigate natural-resistance-associated macrophage protein 1 (NRAMP1), mannose-binding lectin (MBL), vitamin D receptor (VDR) gene polymorphisms and their interaction with susceptibility to pulmonary tuberculosis (PTB) in a Chinese population.MethodsA case-control study was conducted in PTB (n=151), age- and sex- matched healthy controls (HCs) (n=453). Genetic polymorphisms of NRAMP1 (INT4, D543NA and 3′UTR), MBL (HL, PQ, XY and AB) and VDR (FokI and Taq) were analyzed by using PCR-restriction fragment length polymorphism (RFLP) and PCR- single- strand conformation polymorphism (SSCP) techniques. Multifactor dimensionality reduction (MDR) analysis was carried out to assess the effects of the interaction between SNPs.ResultsThe distribution of NRAMP1- 3′UTR (TGTG/del), MBL- HL (H/L) and FokI (F/f) were significantly different between PTB patients and HCs (p<0.05). HPYA (OR: 1.88; 95% CI: 1.22-2.91), LPXA (OR: 3.17; 95% CI: 1.69- 5.96), LQYA (OR: 3.52; 95%CI: 1.50-8.23) and LPYB (OR: 12.37; 95%CI: 3.75- 40.85) of MBL were risk haplotypes for PTB. The TGTG- H- f (OR: 1.70; 95%CI: 1.10-2.62) and del- H-f (OR: 3.48; 95% CI: 1.45-8.37) of 3′UTR- HL- FokI were also high-risk haplotypes associated with tuberculosis.ConclusionsOur study suggests that genotypes of many polymorphic genes are associated with TB, it is necessary to further explore the mechanism of genotypes and gene-gene interaction in susceptibility to tuberculosis

Live-cell vibrational imaging of choline metabolites by stimulated Raman scattering coupled with isotope-based metabolic labeling

Choline is a small molecule that occupies a key position in the biochemistry of all living organisms. Recent studies have strongly implicated choline metabolites in cancer, atherosclerosis and nervous system development. To detect choline and its metabolites, existing physical methods such as magnetic resonance spectroscopy and positron emission tomography are often limited by the poor spatial resolution and substantial radiation dose. Fluorescence imaging, although with submicrometer resolution, requires introduction of bulky fluorophores and thus is difficult in labeling the small choline molecule. By combining the emerging bond-selective stimulated Raman scattering microscopy with metabolic incorporation of deuterated choline, herein we have achieved high resolution imaging of choline-containing metabolites in living mammalian cell lines, primary hippocampal neurons and the multicellular organism C. elegans. Different subcellular distributions of choline metabolites are observed between cancer cells and non-cancer cells, which may reveal a functional difference in the choline metabolism and lipid-mediated signaling events. In neurons, choline incorporation is visualized within both soma and neurites, where choline metabolites are more evenly distributed compared to proteins. Furthermore, choline localization is also observed in the pharynx region of C. elegans larvae, consistent with its organogenesis mechanism. These applications demonstrate the potential of isotope-based stimulated Raman scattering microscopy for future choline-related disease detection and development monitoring in vivo

Study on Ultrasonic Enzyme-Assisted Extraction Process and Antioxidant Activity of Flavonoids from Sedum spectabile boreau flowers

Using Sedum spectabile boreau flowers as raw material, single factor and Box-Behnken response surface test were used to optimize the extraction conditions of Sedum spectabile boreau flavone assisted by ultrasonic enzymatic method, and the antioxidant activity of Sedum spectabile boreau flavone was analyzed in vitro. The results showed that the optimal extraction conditions of total Sedum spectabile boreau flavonoids were ultrasonic action time of 60 min, ethanol concentration of 35%, liquid-solid ratio (ml /g) was 20:1, and the amount of enzyme (cellulase: pectinase =1:1) was 3.2g.The study on the antioxidant activity of total flavonoids of Sedum spectabile boreau flower showed that its antioxidant capacity was gradually enhanced with the increase of the mass concentration of the test, which had a certain dose-effect relationship

A Subsolid Nodules Imaging Reporting System (SSN-IRS) for Classifying 3 Subtypes of Pulmonary Adenocarcinoma

It is essential to identify the subsolid nodules subtype preoperatively to select the optimal treatment algorithm. We developed and validated an imaging reporting system using a classification and regression tree model that based on computed tomography imaging characteristics (291 cases in training group, 146 cases in testing group). The model showed high sensitivity and accuracy of classification. Our model can help clinicians to make follow-up recommendations or decisions for surgery for clinical patients with a subsolid nodule

Quantifying Inactive Lithium in Lithium Metal Batteries

Inactive lithium (Li) formation is the immediate cause of capacity loss and catastrophic failure of Li metal batteries. However, the chemical component and the atomic level structure of inactive Li have rarely been studied due to the lack of effective diagnosis tools to accurately differentiate and quantify Li+ in solid electrolyte interphase (SEI) components and the electrically isolated unreacted metallic Li0, which together comprise the inactive Li. Here, by introducing a new analytical method, Titration Gas Chromatography (TGC), we can accurately quantify the contribution from metallic Li0 to the total amount of inactive Li. We uncover that the Li0, rather than the electrochemically formed SEI, dominates the inactive Li and capacity loss. Using cryogenic electron microscopies to further study the microstructure and nanostructure of inactive Li, we find that the Li0 is surrounded by insulating SEI, losing the electronic conductive pathway to the bulk electrode. Coupling the measurements of the Li0 global content to observations of its local atomic structure, we reveal the formation mechanism of inactive Li in different types of electrolytes, and identify the true underlying cause of low Coulombic efficiency in Li metal deposition and stripping. We ultimately propose strategies to enable the highly efficient Li deposition and stripping to enable Li metal anode for next generation high energy batteries

Astragaloside IV improves slow transit constipation by regulating gut microbiota and enterochromaffin cells

Purpose: Slow transit constipation (STC) is a common gastrointestinal disorder characterized by altered gut microbiota and reduced number of enterochromaffin cells (ECs). Astragaloside IV (AS-IV), a low drug permeability saponin, has showed beneficial effects on patients with STC. However, the specific mechanism by which AS-IV regulates STC remains unclear. In this study, we aimed to investigate the effect of AS-IV on STC and its associated mechanisms involving gut microbiota.Methods: The effect of AS-IV on STC was evaluated on STC mice induced with loperamide. We measured defecation frequency, intestinal mobility, ECs loss, and colonic lesions in STC mice treated with AS-IV. We also analyzed the changes in gut microbiota and metabolites after AS-IV treatment. Moreover, we investigated the relationship between specific gut microbes and altered fecal metabolites, such as 3-bromotyrosine (3-BrY). We also conducted in vitro experiments to investigate the effect of 3-BrY on caspase-dependent apoptosis of ECs and the activation of the p38 MAPK and ERK signaling pathways induced by loperamide.Results: AS-IV treatment promoted defecation, improved intestinal mobility, suppressed ECs loss, and alleviated colonic lesions in STC mice. AS-IV treatment also affected gut microbiota and metabolites, with a significant correlation between specific gut microbes and altered fecal metabolites such as 3-BrY. Furthermore, 3-BrY may potentially reduce caspase-dependent apoptosis of ECs and protect cell survival by inhibiting the activation of the p38 MAPK and ERK signaling pathways induced by loperamide.Conclusion: Our findings suggest that changes in gut microbiota and ECs mediated the therapeutic effect of STC by AS-IV. These results provide a basis for the use of AS-IV as a prebiotic agent for treating STC. The specific mechanism by which AS-IV regulates gut microbiota and ECs warrants further investigation

Single-cell RNA sequencing reveals cellular dynamics and therapeutic effects of astragaloside IV in slow transit constipation

The cellular characteristics of intestinal cells involved in the therapeutic effects of astragaloside IV (AS-IV) for treating slow transit constipation (STC) remain unclear. This study aimed to determine the dynamics of colon tissue cells in the STC model and investigate the effects of AS-IV treatment by single-cell RNA sequencing (scRNA-seq). STC mouse models were developed using loperamide, with subsequent treatment using AS-IV. Colon tissues and feces were collected for scRNA-seq and targeted short-chain fatty acid quantification. We integrated scRNA-seq data with network pharmacology to analyze the effect of AS-IV on constipation. AS-IV showed improvement in defecation for STC mice induced by loperamide. Notably, in STC mice, epithelial cells, T cells, B cells, and fibroblasts demonstrated alterations in cell proportions and aberrant functions, which AS-IV partially rectified. AS-IV has the potential to modulate the metabolic pathway of epithelial cells through its interaction with peroxisome proliferator-activated receptor gamma (PPARγ). AS-IV reinstated fecal butyrate levels and improved energy metabolism in epithelial cells. The proportion of naïve CD4+T cells is elevated in STC, and the differentiation of these cells into regulatory T cells (Treg) is regulated by B cells and fibroblasts through the interaction of ligand-receptor pairs. AS-IV treatment can partially alleviate this trend. The status of fibroblasts in STC undergoes alterations, and the FB_C4_Adamdec1 subset, associated with angiogenesis and the Wingless-related integration (Wnt) pathway, emerges. Our comprehensive analysis identifies perturbations of epithelial cells and tissue microenvironment cells in STC and elucidates mechanisms underlying the therapeutic efficacy of AS-IV

Performance of a deep learning-based lung nodule detection system as an alternative reader in a Chinese lung cancer screening program

Objective: To evaluate the performance of a deep learning-based computer-aided detection (DL-CAD) system in a Chinese low-dose CT (LDCT) lung cancer screening program. Materials and methods: One-hundred-and-eighty individuals with a lung nodule on their baseline LDCT lung cancer screening scan were randomly mixed with screenees without nodules in a 1:1 ratio (total: 360 individuals). All scans were assessed by double reading and subsequently processed by an academic DL-CAD system. The findings of double reading and the DL-CAD system were then evaluated by two senior radiologists to derive the reference standard. The detection performance was evaluated by the Free Response Operating Characteristic curve, sensitivity and false-positive (FP) rate. The senior radiologists categorized nodules according to nodule diameter, type (solid, part-solid, non-solid) and Lung-RADS. Results: The reference standard consisted of 262 nodules ≥ 4 mm in 196 individuals; 359 findings were considered false positives. The DL-CAD system achieved a sensitivity of 90.1% with 1.0 FP/scan for detection of lung nodules regardless of size or type, whereas double reading had a sensitivity of 76.0% with 0.04 FP/scan (P = 0.001). The sensitivity for detection of nodules ≥ 4 - ≤ 6 mm was significantly higher with DL-CAD than with double reading (86.3% vs. 58.9% respectively; P = 0.001). Sixty-three nodules were only identified by the DL-CAD system, and 27 nodules only found by double reading. The DL-CAD system reached similar performance compared to double reading in Lung-RADS 3 (94.3% vs. 90.0%, P = 0.549) and Lung-RADS 4 nodules (100.0% vs. 97.0%, P = 1.000), but showed a higher sensitivity in Lung-RADS 2 (86.2% vs. 65.4%, P < 0.001). Conclusions: The DL-CAD system can accurately detect pulmonary nodules on LDCT, with an acceptable false-positive rate of 1 nodule per scan and has higher detection performance than double reading. This DL-CAD system may assist radiologists in nodule detection in LDCT lung cancer screening

Validation of the Oxford classification of IgA nephropathy for pediatric patients from China

BACKGROUND: The Oxford classification of IgA nephropathy (IgAN) provides a useful tool for prediction of renal prognosis. However, the application of this classification in children with IgAN needs validation in different patient populations. METHODS: A total of 218 children with IgAN from 7 renal centers in China were enrolled. The inclusion criteria was similar to the original Oxford study. RESULTS: There were 98 patients (45%) with mesangial proliferation (M1), 51 patients (23%) with endocapillary proliferation (E1), 136 patients (62%) with segmental sclerosis/adhesion lesion (S1), 13 patients (6%) with moderate tubulointerstitial fibrosis (T1 26-50% of cortex scarred), and only 2 patients (1%) with severe tubulointerstitial fibrosis (T2, >50% of cortex scarred). During a median follow-up duration of 56 months, 24 children (12.4%) developed ESRD or 50% decline in renal function. In univariate COX analysis, we found that tubular atrophy/interstitial fibrosis (HR 4.3, 95%CI 1.8-10.5, P < 0.001) and segmental glomerulosclerosis (HR 9.2 1.2-68.6, P = 0.03) were significant predictors of renal outcome. However, mesangial hypercellularity, endocapillary proliferation, crescents, and necrosis were not associated with renal prognosis. In the multivariate COX regression model, none of these pathologic lesions were shown to be independent risk factors of unfavorable renal outcome except for tubular atrophy/interstitial fibrosis (HR 2.9, 95%CI 1.0-7.9 P = 0.04). CONCLUSIONS: We confirmed tubular atrophy/interstitial fibrosis was the only feature independently associated with renal outcomes in Chinese children with IgAN