Prognostic and therapeutic model based on disulfidptosis-related genes for patients with clear cell renal cell carcinoma.

Disulfidptosis, a newly discovered mode of cell death caused by excessive accumulation of intracellular disulfide compounds, is closely associated with tumor development. This study focused on the relationship between disulfidptosis and clear cell renal cell carcinoma (ccRCC). Firstly, the characterizations of disulfidptosis-related genes (DRGs) in ccRCC were showed, which included number variation (CNV), single nucleotide variation (SNV), DNA methylation, mRNA expression and gene mutation. Then, the ccRCC samples were classified into three clusters through unsupervised clustering based on DRGs. Survival and pathway enrichment differences were evaluated among the three clusters. Subsequently, the differentially expressed genes (DEGs) among the three clusters were screened by univariate Cox, LASSO, and multivariate Cox analysis, and five key DEGs were obtained. Based on the five key DEGs, the ccRCC samples were reclassified into two geneclusters and the survival differences and immune cell infiltration between two geneclusters was investigated. In next step, ccRCC samples were divided into two groups according to PCA scores of five key DEGs, namely high PCA score group (HPSG) and low PCA score group (LPSG). On this basis, differences in survival prognosis, immune cell infiltration and correlation with immune checkpoint, as well as differences in sensitivity to targeted drugs were compared between HPSG and LPSG. The expression levels of four immune checkpoints were higher in HPSG than in LPSG, whereas the LPSG was more sensitive to targeted drug therapy than the HPSG. Finally, validation experiments on HDAC4 indicated that HDAC4 could increase the proliferation and colony formation ability of ccRCC cells.

Cd(II)-based complex loaded with drug doxorubicin hydrogels against leukemia and reinforcement learning.

A new 3D metal-organic frameworks [Cd6(L)4(bipy)3(H2O)2·H2O] (1) was gained by employing Cd(II) and organic ligand [H3L = 4,4',4''-(benzene-1,3,5-triyltris(oxy))tribenzoic acid)benzene acid; bipy = 4,4'-bipyridine] in the solvothermal condition, which has been fully examined via single-X ray diffraction, FTIR and elemental analysis and so on. Using natural polysaccharides hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) as raw materials, we successfully prepared HA/CMCS hydrogels and observed their internal micromorphology by scanning electron microscopy. Using doxorubicin (Dox) as a drug model, we synthesized a novel metal gel particle loaded with doxorubicin, and their encapsulation and release effects were studied using fluorescence spectroscopy, followed by further investigation of their components through thermogravimetric analysis. Based on this, the therapeutic effect on leukemia was evaluated. Finally, an enhanced learning method for automatically designing new ligand structures from host ligands was proposed. Through generative modeling and molecular docking simulations, the biological behavior of the host and predicted cadmium complexes was extensively studied.

The collective dynamics of frustrated biological neuron networks.

To maintain normal functionality, it is necessary for a multicellular organism to generate robust responses to external temporal signals. However, the underlying mechanisms to coordinate the collective dynamics of cells remain poorly understood. Here we study the calcium activity of micropatterned biological neuron networks excited by periodic ATP stimuli. Combining quantitative experiments, physical and biological manipulation of cells, as well as mathematical modeling, we show that isolated cells in a network become more synchronized at longer period of stimuli through noise cancellation. However, slowly varying external signal also increases gap junction coupling between connected nodes in the network; and gap junction mediated communication may destroy network synchronization due to special nonlinear bifurcations exhibited by the excitable dynamics of neuronal cells. Based on our results, we propose that a biological neuron network supported by gap junctional communication encodes external temporal signals in its network dynamics. A sparely connected network approaches synchronization as input signal slows down, whereas a highly connected network enters dynamic frustration in the same situation.

Optimal diagnostic approach for using CT-derived quantitative flow ratio in patients with stenosis on coronary computed tomography angiography.

BACKGROUND: Coronary computed tomography angiography (CCTA)-derived quantitative flow ratio (CT-QFR) is an on-site non-invasive technique estimating invasive fractional flow reserve (FFR). This study assesses the diagnostic performance of using most distal CT-QFR versus lesion-specific CT-QFR approach for identifying hemodynamically obstructive coronary artery disease (CAD). METHODS: Prospectively enrolled de novo chest pain patients (n â€‹= â€‹445) with ≥50 â€‹% visual diameter stenosis on CCTA were referred for invasive evaluation. On-site CT-QFR was analyzed post-hoc blinded to angiographic data and obtained as both most distal (MD-QFR) and lesion-specific CT-QFR (LS-QFR). Abnormal CT-QFR was defined as ≤0.80. Hemodynamically obstructive CAD was defined as invasive FFR ≤0.80 or ≥70 â€‹% diameter stenosis by 3D-quantitative coronary angiography. RESULTS: In total 404/445 patients had paired CT-QFR and invasive analyses of whom 149/404 (37 â€‹%) had hemodynamically obstructive CAD. MD-QFR and LS-QFR classified 188 (47 â€‹%) and 165 (41 â€‹%) patients as abnormal, respectively. Areas under the receiver-operating characteristic curve for MD-QFR was 0.83 vs. 0.85 for LS-QFR, p â€‹= â€‹0.01. Sensitivities for MD-QFR and LS-QFR were 80 â€‹% (95%CI: 73-86) vs. 77 â€‹% (95%CI: 69-83), p â€‹= â€‹0.03, respectively, and specificities were 73 â€‹% (95%CI: 67-78) vs. 80 â€‹% (95%CI: 75-85), p â€‹< â€‹0.01, respectively. Positive predictive values for MD-QFR and LS-QFR were 63 â€‹% vs. 69 â€‹%, p â€‹< â€‹0.01, respectively, and negative predictive values for MD-QFR and LS-QFR were 86 â€‹% vs. 85 â€‹%, p â€‹= â€‹0.39, respectively). CONCLUSION: Using a lesion-specific CT-QFR approach has superior discrimination of hemodynamically obstructive CAD compared to a most distal CT-QFR approach. CT-QFR identified most cases of hemodynamically obstructive CAD while a normal CT-QFR excluded hemodynamically obstructive CAD in the majority of patients.

The value of shear wave elasticity and shear wave dispersion imaging to evaluate the viscoelasticity of renal parenchyma in children with glomerular diseases.

BACKGROUND: To study the value of shear wave elasticity and shear wave dispersion imaging to evaluate the viscoelasticity of renal parenchyma in children with glomerular diseases. METHODS: Forty-three children with glomerular diseases were prospectively evaluated by shear wave elasticity (SWE) and shear wave dispersion imaging (SWD); 43 healthy volunteers served as the control group. The shear wave velocities (SWV) and the dispersion slopes were measured at the upper, middle, and lower poles of both kidneys. The analysis of mean SWV and mean dispersion slope in control and patient groups was used to further evaluate the value of SWE and SWD in the viscoelasticity of renal parenchyma in children with glomerular disease. RESULTS: The mean SWV in children with glomerular disease was higher than that in the healthy control group (1.61 ± 0.09 m/s vs. 1.43 ± 0.07 m/s, p < 0.001). Compared with healthy group, the mean dispersion slope in children with glomerular disease was significantly increased (13.5 ± 1.39 (m/s)/kHz vs. 12.4 ± 1.40 (m/s)/kHz, p < 0.001). Correlation analysis showed absence of correlation between the SWV and dispersion slope of occult blood, serum creatinine, 24-h urine protein, blood albumin, BMI and ROI box depth of children with glomerular disease. CONCLUSIONS: The present study shows that it is feasible to use SWE and SWD to evaluate the difference of viscoelasticity of the renal parenchyma between healthy children and those with glomerular disease.

Synergy Effect between Fruity Esters and Potential Odorants on the Aroma of Hutai-8 Rose Wine Revealed by Threshold, S-Curve, and σ-τ Plot Methods.

To analyze the contribution of fruity esters on wine aroma perception, the interaction levels between 12 esters and key odorants of Hutai-8 rose wine were investigated using threshold, S-curve, and σ-τ plot methods, and the aroma enhancement performance of esters was verified by using addition experiments. Results indicated that esters enhance the sweet, floral, and fruity traits of citronellol, ß-damascenone, and nerolidol, especially at subthreshold levels. Meanwhile, esters increased the floral and fruity characteristics of key fermentative odorants mainly by additive effects, with acetate esters possessing a better synergy ability. In contrast, the synergy levels between binary esters were less influenced by the concentration but more by the compound structure and aroma. Additionally, moderately subjoining the type and content of esters in wine proved that their synergy effects improved the sweet trait and decreased the sour fruit trait. This finding characterized that the contribution of esters to the wine aroma was obtained by the combined synergy of odorants at a suitable concentration.

Does Accountability Aggravate the Risk of Teacher Burnout? Evidence from the Chinese Education System.

External and internal accountabilities and emotional labor are possible factors triggering teacher burnout, but the relationships between the constructs have not been fully addressed. Thus, this study aimed to construct and test a chain mediation model to demonstrate the relationships between external accountability and burnout, mediated by internal accountability and emotional labor sequentially. By surveying 814 teachers (years of teaching: M = 13.42, SD = 10.97) from 10 provinces in China, it shows: (1) external and internal accountabilities are both negatively related to burnout; (2) internal accountability, deep acting, and expression of naturally felt emotions mediate the relationship between external accountability and burnout; (3) internal accountability and surface acting sequentially play a chain mediating role between external accountability and burnout; and (4) internal accountability and expression of naturally felt emotions sequentially play a chain mediating role between external accountability and teacher burnout.

First Report of Diaporthe pseudophoenicicola causing Leaf Blight on Pecan in China.

Pecan (Carya illinoinensis) is one of the important economic forest crops widely cultivated in Jiangsu Provinces, China. From August to September in both 2021 and 2022, a foliar blight was observed in 7-ha and 6-ha pecan orchards in Changzhou (31°58'9.6″ N, 119°48'33.84″ E), and Jurong (31°52'15.46″ N, 119°9'24.62″ E), Jiangsu Province. The disease severity was about 32% with 8% incidence on 120 surveyed trees of the two orchards. Typical symptoms were lesions with a dark-brown color, which later became brown. We collected eighteen pecan leaves with typical symptoms in the surveyed pecan orchards and took them back to the laboratory for identification. Small fragments (approximately 9 mm2) from the necrotic borders of infected leaves were surfaced sterilized, plated on potato dextrose agar (PDA) and then incubated in darkness at 25°C. Pure cultures were obtained by single-spore culture. Thirty-three isolates with similar characteristics were obtained from the infected leaves (isolation frequency 85%), and the colonies surface on PDA was ochreous with patchs of olivaceous-yellow and sparse aerial mycelium. Observing from the back of the plate, the colonies were cream-yellow. Two types of single-cell conidia were produced on PDA. Alpha-conidia were 7.4 (range, 5.9 to 8.8) × 2.1 (range, 1.6 to 2.8) µm (n = 100), aseptate, smooth, fusiform, straight and tapering towards both ends. Beta-conidia were 25.1 (range, 19.1 to 36.2) × 1.3 (range, 1.0 to 2) µm (n = 100), filiform, hyaline, aseptate and curved at one end. The morphological features of these isolates agreed with those of Diaporthe sp. (Gomes et al. 2013; Gao et al. 2017). To further identify the isolates, the regions of internal transcribed spacer (ITS, OR214967 to OR214969), calmodulin (CAL, OR228558 to OR228560), translation elongation factor 1-α (EF1a, OR228561 to OR228563), histone H3 (HIS, OR228564 to OR228566), and beta-tubulin 2 (TUB2, OR228567 to OR228569) were amplified and sequenced from genomic DNA for the three representative isolates (LSM1, LSM2 and LSM3), respectively (Gomes et al. 2013). Multilocus phylogenetic analysis revealed that the three isolates and D. pseudophoenicicola were clustered in the same clade. Based on the results of morphological and molecular analysis, these isolates were identified as D. pseudophoenicicola. The pathogenicity of three isolates were tested on leaves of pecan seedlings. The conidial suspension (1 × 105 conidia/ml) of each isolate was sprayed evenly on the surface of leaves of three healthy seedlings. Sterilized distilled water was used for negative controls. Finally, all inoculated plants were kept in a greenhouse at 28°C under 100% relative humidity. Two weeks after inoculation, the inoculated plants developed symptoms similar to those of the original diseased plants, while controls remained asymptomatic. D. pseudophoenicicola were re-isolated from from inoculated plants. The pathogenicity experiment was repeated three times. Previously, D. pseudophoenicicola has been reported to cause stem-end browning disease in ripe mango (Takushi et al. 2016; Xu et al 2022). To our knowledge, this is the first report of D. pseudophoenicicola causing leaf blight on pecan . This study provides important information for developing effective pecan disease management practices.

A novel model based on disulfidptosis-related genes to predict prognosis and therapy of bladder urothelial carcinoma.

PURPOSE: Disulfidptosis is a novel type of cell death induced by disulphide stress that depends on the accumulation of cystine disulphide, causing cytotoxicity and triggering cell death. However, the direct prognostic effect and regulatory mechanism of disulfidptosis-related genes in bladder urothelial carcinoma (BLCA) remain unclear. METHODS: To explore the role of 10 disulfidptosis-related genes, the multiomic data of 10 genes were comprehensively analysed. Next, based on seven disulfidptosis-related differentially expressed genes, a novel disulfidptosis-related gene score was developed to help predict the prognosis of BLCA. Immunohistochemistry, EDU, Real-time PCR and western blot were used to verify the model. RESULTS: Significant functional differences were found between the high- and low-risk score groups, and samples with a higher risk score were more malignant. Furthermore, the tumour exclusion and Tumour Immune Dysfunction and Exclusion scores of the high-risk score group were higher than those of the low-risk score group. The risk score was positively correlated with the expression of immune checkpoints. Drug sensitivity analyses revealed that the low-risk score group had a higher sensitivity to cisplatin, doxorubicin, docetaxel and gemcitabine than the high-risk score group. Moreover, the expression of the TM4SF1 was positively correlated with the malignancy degree of BLCA, and the proliferation ability of BLCA cells was reduced after knockdown TM4SF1. CONCLUSION: The present study results suggest that disulfidptosis-related genes influence the prognosis of BLCA through their involvement in immune cell infiltration. Thus, these findings indicate the role of disulfidptosis in BLCA and its potential regulatory mechanisms.

Bidirectional Trust-Enhanced Collaborative Filtering for Point-of-Interest Recommendation.

A personalized point-of-interest (POI) recommender system is of great significance to facilitate the daily life of users. However, it suffers from some challenges, such as trustworthiness and data sparsity problems. Existing models only consider the trust user influence and ignore the role of the trust location. Furthermore, they fail to refine the influence of context factors and fusion between the user preference and context models. To address the trustworthiness problem, we propose a novel bidirectional trust-enhanced collaborative filtering model, which investigates the trust filtering from the views of users and locations. To tackle the data sparsity problem, we introduce temporal factor into the trust filtering of users as well as geographical and textual content factors into the trust filtering of locations. To further alleviate the sparsity of user-POI rating matrices, we employ a weighted matrix factorization fused with the POI category factor to learn the user preference. To integrate the trust filtering models and the user preference model, we develop a fused framework with two kinds of integrating methods in relation to the different impacts of factors on the POIs that users have visited and the POIs that users have not visited. Finally, we conduct extensive experiments on Gowalla and Foursquare datasets to evaluate our proposed POI recommendation model, and the results show that our proposed model improves by 13.87% at precision@5 and 10.36% at recall@5 over the state-of-the-art model, which demonstrates that our proposed model outperforms the state-of-the-art method.

Advances in Diagnosis, Therapy, and Prognosis of Coronary Artery Disease Powered by Deep Learning Algorithms.

Percutaneous coronary intervention has been a standard treatment strategy for patients with coronary artery disease with continuous ebullient progress in technology and techniques. The application of artificial intelligence and deep learning in particular is currently boosting the development of interventional solutions, improving the efficiency and objectivity of diagnosis and treatment. The ever-growing amount of data and computing power together with cutting-edge algorithms pave the way for the integration of deep learning into clinical practice, which has revolutionized the interventional workflow in imaging processing, interpretation, and navigation. This review discusses the development of deep learning algorithms and their corresponding evaluation metrics together with their clinical applications. Advanced deep learning algorithms create new opportunities for precise diagnosis and tailored treatment with a high degree of automation, reduced radiation, and enhanced risk stratification. Generalization, interpretability, and regulatory issues are remaining challenges that need to be addressed through joint efforts from multidisciplinary community.

ANGPTL4 promotes nephrotic syndrome by downregulating podocyte expression of ACTN4 and podocin.

BACKGROUND: lipopolysaccharide (LPS) can induce nephrotic syndrome-like features such as massive proteinuria, hyperlipidemia, and fusion of glomerular podocytes with foot processes (FPs) in mice. Angiopoietin-like protein 4 (ANGPTL4) neutralized the negative charge of glomerular basement membrane charge and aggravated renal injury. The mechanism of ANGPTL4 aggravating podocyte injury has not been well clarified. In this study, we aimed to investigate the potential role of ANGPTL4 on podocyte FPs fusion and podocyte signal molecules. METHODS: We built angptl4 gene knocked out in C57BL6 mice using CRISPR/Cas9 technique. Nephrotic model was built by LPS in wild type and angptl4-/- mice. Expression of ACTN4, podocin and TRPC6 in the glomerulus were determined by immunohistochemistry. RESULTS: In physical condition, the wild type and angptl4-/- mice showed no significant differences in biochemical indicators and kidney pathology. But in nephrotic condition, compared with wild type mice hyperlipidemia and proteinuria with the angptl4-/- mice was significantly relieved. Moreover, the degree of FPs fusion was notably improved in the nephrotic mice knocked out angptl4 gene. Expression of ACTN4 and podocin decreased drastically in the glomerulus of wild-type nephrotic mice. Different from wild-type, the ACTN4 and podocin expression showed slight weakening in angptl4-/- nephrotic mice. As transient receptor potential cation channel subfamily member, TRPC6 expression had no visible change in glomerulus of each group. CONCLUSIONS: ANGPTL4 induces hyperlipidemia and podocyte injury in nephrotic mice, thereby promoting the formation of proteinuria. Its molecular mechanism may be related to ANGPTL4 down-regulating actin cytoskeletal regulatory signals ACTN4 and podocin.

EAGS: An extracting auxiliary knowledge graph model in multi-turn dialogue generation.

Multi-turn dialogue generation is an essential and challenging subtask of text generation in the question answering system. Existing methods focused on extracting latent topic-level relevance or utilizing relevant external background knowledge. However, they are prone to ignore the fact that relying too much on latent aspects will lose subjective key information. Furthermore, there is not so much relevant external knowledge that can be used for referencing or a graph that has complete entity links. Dependency tree is a special structure that can be extracted from sentences, it covers the explicit key information of sentences. Therefore, in this paper, we proposed the EAGS model, which combines the subjective pivotal information from the explicit dependency tree with sentence implicit semantic information. The EAGS model is a knowledge graph enabled multi-turn dialogue generation model, and it doesn't need extra external knowledge, it can not only extract and build a dependency knowledge graph from existing sentences, but also prompt the node representation, which is shared with Bi-GRU each time step word embedding in node semantic level. We store the specific domain subgraphs built by the EAGS, which can be retrieved as external knowledge graph in the future multi-turn dialogue generation task. We design a multi-task training approach to enhance semantics and structure local feature extraction, and balance with the global features. Finally, we conduct experiments on Ubuntu large-scale English multi-turn dialogue community dataset and English Daily dialogue dataset. Experiment results show that our EAGS model performs well on both automatic evaluation and human evaluation compared with the existing baseline models.

Temporal signals drive the emergence of multicellular information networks.

Coordinated responses to environmental stimuli are critical for multicellular organisms. To overcome the obstacles of cell-to-cell heterogeneity and noisy signaling dynamics within individual cells, cells must effectively exchange information with peers. However, the dynamics and mechanisms of collective information transfer driven by external signals are poorly understood. Here we investigate the calcium dynamics of neuronal cells that form confluent monolayers and respond to cyclic ATP stimuli in microfluidic devices. Using Granger inference to reconstruct the underlying causal relations between the cells, we find that the cells self-organize into spatially decentralized and temporally stationary networks to support information transfer via gap junction channels. The connectivity of the causal networks depends on the temporal profile of the external stimuli, where short periods, or long periods with small duty fractions, lead to reduced connectivity and fractured network topology. We build a theoretical model based on communicating excitable units that reproduces our observations. The model further predicts that connectivity of the causal network is maximal at an optimal communication strength, which is confirmed by the experiments. Together, our results show that information transfer between neuronal cells is externally regulated by the temporal profile of the stimuli and internally regulated by cell-cell communication.

ANGPTL3 is involved in kidney injury in high-fat diet-fed mice by suppressing ACTN4 expression.

OBJECTIVE: We wanted to explore how angiopoietin-like 3 (ANGPTL3) impact hyperlipidemia-induced renal injury. METHODS: ANGPTL3 knockout mice and wild-type C57 mice were set up in four groups (N = 5) depending on a normal or 60% high-fat diet: wild-type with normal diet (WT), angptl3-/- with normal diet (KO), wild-type + high-fat diet (WT + HF) and angptl3-/- + high-fat diet (KO + HF). The detection time points were the 9th, 13th, 17th and 21st weeks after modeling. Serum lipid and urinary protein levels of mice in each group were detected, and pathological changes in the kidney were analyzed. Moreover, the expression of ANGPTL3, α-actinin-4 (ACTN4), CD2-associated protein (CD2AP) and podocin was tested in the glomerulus by immunohistochemistry (IHC). RESULTS: In the WT + HF group, hyperlipidemia and proteinuria could be observed at the 9th week and were gradually aggravated with time. Compared with WT + HF mice, the levels of serum lipids and proteinuria in KO + HF mice were significantly reduced, and the width of podocyte foot processes (FPs) fusion was also markedly improved. The IHC results suggested that in WT + HF mice, the expression of ANGPTL3 was significantly enhanced. After modeling, ACTN4 expression was markedly weakened in the glomeruli of WT + HF mice. Different to WT mice, ACTN4 expression was not observed obviously change in KO + HF mice. Compared with the normal diet group, the expression of podocin showed a decline in WT mice treated with high-fat diet and showed a significant difference from the 17th week. In addition, podocin expression in KO + HF glomeruli was also found to be weak but not significantly different from that in WT + HF glomeruli at the four time points. The expression of CD2AP showed similar results among the four groups. CONCLUSION: ANGPTL3 could play a role in the mechanism of hyperlipidemia-associated podocyte injury via ACTN4.

Emergence of synchronized multicellular mechanosensing from spatiotemporal integration of heterogeneous single-cell information transfer.

Multicellular synchronization is a ubiquitous phenomenon in living systems. However, how noisy and heterogeneous behaviors of individual cells are integrated across a population toward multicellular synchronization is unclear. Here, we study the process of multicellular calcium synchronization of the endothelial cell monolayer in response to mechanical stimuli. We applied information theory to quantify the asymmetric information transfer between pairs of cells and defined quantitative measures to how single cells receive or transmit information within a multicellular network. Our analysis revealed that multicellular synchronization was established by gradual enhancement of information spread from the single cell to the multicellular scale. Synchronization was associated with heterogeneity in the cells' communication properties, reinforcement of the cells' state, and information flow. Altogether, we suggest a phenomenological model where cells gradually learn their local environment, adjust, and reinforce their internal state to stabilize the multicellular network architecture to support information flow from local to global scales toward multicellular synchronization.

Comparison of coronary CT angiography-based and invasive coronary angiography-based quantitative flow ratio for functional assessment of coronary stenosis: A multicenter retrospective analysis.

BACKGROUND: The aim of this study was to evaluate the diagnostic performance of coronary CT angiography (CTA)-based quantitative flow ratio (QFR), namely CT-QFR, and compare it with invasive coronary angiography (ICA)-based Murray law QFR (µQFR), using fractional flow reserve (FFR) as the reference standard. METHODS: Patients who underwent coronary CTA, ICA and pressure wire-based FFR assessment within two months were retrospectively analyzed. CT-QFR and µQFR were computed in blinded fashion and compared with FFR, all applying the same cut-off value of ≤0.80 to identify hemodynamically significant stenosis. RESULTS: Paired comparison between CT-QFR and µQFR was performed in 191 vessels from 167 patients. Average FFR was 0.81 â€‹± â€‹0.10 and 42.4% vessels had an FFR ≤0.80. CT-QFR had a slightly lower correlation with FFR compared with µQFR, although statistically non-significant (r â€‹= â€‹0.87 versus 0.90, p â€‹= â€‹0.110). The vessel-level diagnostic performance of CT-QFR was slightly lower but without statistical significance than µQFR (AUC â€‹= â€‹0.94 versus 0.97, difference: -0.03 [95%CI: -0.00-0.06], p â€‹= â€‹0.095), and substantially higher than diameter stenosis by CTA (AUC difference: 0.17 [95%CI: -0.10-0.23], p â€‹< â€‹0.001). The patient-level diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio for CT-QFR to identify FFR value â€‹≤ â€‹0.80 was 88%, 90%, 86%, 86%, 91%, 6.59 and 0.12, respectively. The diagnostic accuracy of CT-QFR was 84% in extensively calcified lesions, while in vessels with no or less calcification, CT-QFR showed a comparable diagnostic accuracy with µQFR (91% versus 92%, p â€‹= â€‹0.595). Intra- and inter-observer variability in CT-QFR analysis was -0.00 â€‹± â€‹0.04 and 0.00 â€‹± â€‹0.04, respectively. CONCLUSIONS: Performance in diagnosis of hemodynamically significant coronary stenosis by CT-QFR was slightly lower but without statistical significance than µQFR, and substantially higher than CTA-derived diameter stenosis. Extensively calcified lesions reduced the diagnostic accuracy of CT-QFR.

Full-length gonad transcriptome analysis of Amur sturgeon Dmrt family genes: identification, characterization, and expression patterns during gonadal differentiation.

The regulatory mechanisms that govern sex differentiation in sturgeon are still poorly understood. The doublesex and Mab-3-related transcription factor (Dmrt) gene family is known for its extensive roles in sex determination and differentiation across vertebrates. This study aimed to identify new members of sturgeon Dmrt family genes and core actors in the gonadal differentiation of Amur sturgeon. A full-length gonad transcriptome database was exploited to identify Dmrt gene orthologs. Analyses of phylogenetic relationships and selection pressure were performed, and tissue expression profiles and spatiotemporal expression patterns in gonads were then analyzed using real-time PCR. In total, five Dmrt family genes were identified from the full-length gonad transcriptome, including Dmrt2, DmrtA1, DmrtA2, DmrtB1a, and DmrtB1b. Phylogenetic analysis showed that these genes were clustered into clades corresponding to the doublesex/Mav-3 (DM) genes of vertebrates. Furthermore, the analysis of evolutionary selective pressure indicated that DmrtB1a and DmrtB1b were subject to positive selection, suggesting the existence of adaptive evolution in sturgeon. The extensive tissue expression profiling of each Dmrt family gene revealed typical characteristics. Remarkably, according to a spatiotemporal expression pattern analysis, in later stages, DmrtB1b expression increased in testes and was significantly higher in testes than in ovaries at 24 months after hatching (M) and 36 M. This study provides a genetic resource of full-length Dmrt family genes and increases the understanding of Dmrt functions in sex differentiation in sturgeon.

ANGPTL3 impacts proteinuria and hyperlipidemia in primary nephrotic syndrome.

BACKGROUND: It is unclear why primary nephrotic syndrome (PNS) patients often have dyslipidemia. Recent studies have shown that angiopoietin-like protein 3 (ANGPTL3) is an important regulator of lipid metabolism. In this study, we explored how ANGPTL3 impacts dyslipidemia during PNS development. METHODS: We measured the serum levels of ANGPTL3 in PNS patients (n=196). Furthermore, the degree of proteinuria and lipid metabolism were examined in angptl3-overexpressing transgenic (angptl3-tg) mice at different ages. Moreover, in this study, we used the clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) system to create angptl3-knockout (angptl3-/-) mice to investigate lipopolysaccharide (LPS)-induced nephrosis. RESULTS: Compared with that in the healthy group, the serum level of ANGPTL3 in the PNS group was significantly increased (32 (26.35-39.66) ng/ml vs. 70.44 (63.95-76.51) ng/ml, Z =-4.81, P < 0.001). There were significant correlations between the serum level of ANGPTL3 and the levels of cholesterol (r=0.34, P < 0.001), triglycerides (r= 0.25, P = 0.001) and low-density lipoprotein (r= 0.50, P < 0.001) in PNS patients. With increasing age, angptl3-tg mice exhibited increasingly severe hypertriglyceridemia and proteinuria. The pathological features of angptl3-tg mice included rich lipid droplet deposition in hepatocytes and diffuse podocyte effacement. Compared to wild-type mice, angptl3-/- mice showed significantly lower degrees of lipid dysfunction and proteinuria after stimulation with LPS. The effects of ANGPTL3 on nephrotic dyslipidemia were confirmed in cultured hepatocytes subjected to angptl3 knockdown or overexpression. Finally, significant alterations in lipoprotein lipase (LPL) levels were observed in liver tissues from Angptl3-/- and wild-type mice stimulated with LPS. CONCLUSIONS: ANGPTL3 could be involved in the development of dyslipidemia, as well as proteinuria, during PNS pathogenesis. Inhibition of LPL expression may the mechanism by which ANGPTL3 induces hyperlipidemia in PNS.

Responsibility optimization of a high-speed InP/InGaAs photodetector with a back reflector structure.

Top-illuminated PIN photodetectors (PDs) are widely utilized in telecommunication systems, and more efforts have been focused on optimizing the optical responsibility and bandwidth for high-speed and capacity applications. In this work, we develop an integrated top-illuminated InP/InGaAs PIN PD with a back reflector by using a microtransfer printing (µ-TP) process. An improved µ-TP process, where the tether of silicon nitride instead of photoresist, is selected to support an underetched III-V device on an InP substrate before transfer. According to theoretical simulations and experimental measurements, the seamless integration of the PD with a back reflector through µ-TP process makes full use of the 2nd or even multiple reflecting light in the absorption layer to optimize the maximum responsibility. The integrated device with a 5 µm square p-mesa possesses a high optical responsibility of 0.78 A/W and 3 dB bandwidth of 54 GHz using a 500 nm i-InGaAs absorption layer. The present approach for top-illuminated PIN PDs demonstrates an advanced route in which a thin intrinsic layer is available for application in high-performance systems.