Immune persistence after different polio sequential immunization schedules in Chinese infants.

Trivalent oral poliovirus vaccine (tOPV) has been withdrawn and instead an inactivated poliovirus vaccine (IPV) and bivalent type 1 and type 3 OPV (bOPV) sequential immunization schedule has been implemented since 2016, but no immune persistence data are available for this polio vaccination strategy. This study aimed to assess immune persistence following different polio sequential immunization schedules. Venous blood was collected at 24, 36, and 48 months of age from participants who had completed sequential schedules of combined IPV and OPV in phase III clinical trials. The serum neutralizing antibody titers against poliovirus were determined, and the poliovirus-specific antibody-positive rates were evaluated. A total of 1104 participants were enrolled in this study. The positive rates of poliovirus type 1- and type 3-specific antibodies among the sequential immunization groups showed no significant difference at 24, 36, or 48 months of age. The positive rates of poliovirus type 2-specific antibody in the IPV-IPV-tOPV group at all time points were nearly 100%, which was significantly higher than the corresponding rates in other immunization groups (IPV-bOPV-bOPV and IPV-IPV-bOPV). Immunization schedules involving one or two doses of IPV followed by bOPV failed to maintain a high positive rate for poliovirus type 2-specific antibody.

The ubiquitin E3 ligase BFAR promotes degradation of PNPLA3.

A missense variant in patatin-like phospholipase domain-containing protein 3 [PNPLA3(I148M)] is the most impactful genetic risk factor for fatty liver disease (FLD). We previously showed that PNPLA3 is ubiquitylated and subsequently degraded by proteasomes and autophagosomes and that the PNPLA3(148M) variant interferes with this process. To define the machinery responsible for PNPLA3 turnover, we used small interfering (si)RNAs to inactivate components of the ubiquitin proteasome system. Inactivation of bifunctional apoptosis regulator (BFAR), a membrane-bound E3 ubiquitin ligase, reproducibly increased PNPLA3 levels in two lines of cultured hepatocytes. Conversely, overexpression of BFAR decreased levels of endogenous PNPLA3 in HuH7 cells. BFAR and PNPLA3 co-immunoprecipitated when co-expressed in cells. BFAR promoted ubiquitylation of PNPLA3 in vitro in a reconstitution assay using purified, epitope-tagged recombinant proteins. To confirm that BFAR targets PNPLA3, we inactivated Bfar in mice. Levels of PNPLA3 protein were increased twofold in hepatic lipid droplets of Bfar-/- mice with no associated increase in PNPLA3 mRNA levels. Taken together these data are consistent with a model in which BFAR plays a role in the post-translational degradation of PNPLA3. The identification of BFAR provides a potential target to enhance PNPLA3 turnover and prevent FLD.

The Protective Role of Dietary Polyphenols in Urolithiasis: Insights into Antioxidant Effects and Mechanisms of Action.

Urolithiasis is a common urological disease with increasing prevalence and high recurrence rates around the world. Numerous studies have indicated reactive oxygen species (ROS) and oxidative stress (OS) were crucial pathogenic factors in stone formation. Dietary polyphenols are a large group of natural antioxidant compounds widely distributed in plant-based foods and beverages. Their diverse health benefits have attracted growing scientific attention in recent decades. Many literatures have reported the effectiveness of dietary polyphenols against stone formation. The antiurolithiatic mechanisms of polyphenols have been explained by their antioxidant potential to scavenge free radicals and ROS, modulate the expression and the activity of endogenous antioxidant and prooxidant enzymes, regulate signaling pathways associated with OS, and maintain cell morphology and function. In this review, we first describe OS and its pathogenic effects in urolithiasis and summarize the classification and sources of dietary polyphenols. Then, we focus on the current evidence defining their antioxidant potential against stone formation and put forward challenges and future perspectives of dietary polyphenols. To conclude, dietary polyphenols offer potential applications in the treatment and prevention of urolithiasis.

Identification of Two Clusters in Renal Pelvis Urobiome of Unilateral Stone Formers Using 2bRAD-M.

Urolithiasis is a common urological disease with increasing incidence and a high recurrence rate, whose etiology is not fully understood. The application of sequencing and culturomics has revealed that urolithiasis is closely related to the urinary microbiome (urobiome), shedding new light on the pathogenesis of stone formation. In this study, we recruited 30 patients with unilateral stones and collected their renal pelvis urine from both sides. Then, we performed 2bRAD-M, a novel sequencing technique that provides precise microbial identification at the species level, to characterize the renal pelvis urobiome of unilateral stone formers in the both sides. We first found that the urobiome in the stone side could be divided into two clusters (Stone1 and Stone2) based on distance algorithms. Stone2 harbored higher microbial richness and diversity compared to Stone1. The genera Cupriavidus and Sphingomonas were overrepresented in Stone1, whereas Acinetobacter and Pseudomonas were overrepresented in Stone2. Meanwhile, differential species were identified between Stone1 and Stone2. We further constructed a random forest model to discriminate two clusters which achieved a powerful diagnostic potential. Moreover, the urobiome of the non-stone side (Control1/2) was compared with that of the stone side (Stone1/2). Stone1 and Control1 showed different microbial community distributions, while Stone2 was similar to Control2 based on diversity analysis. We also identified differentially abundant species among all groups. We assumed that there might be different mechanisms of how microbiota contribute to stone formation in two clusters. Our findings might assist in the selection of suitable medical treatments for urolithiasis.

Retraction Notice to: lncRNA ILF3-AS1 promotes proliferation and metastasis of colorectal cancer cells by recruiting histone methylase EZH2.

[This retracts the article DOI: 10.1016/j.omtn.2021.04.007.].

Inhibition of AT1R/IP3/IP3R-mediated Ca2+ release protects against calcium oxalate crystals-induced renal oxidative stress.

Calcium oxalate (CaOx) stones are the most prevalent type of kidney stones. CaOx crystals can stimulate reactive oxygen species (ROS) generation and induce renal oxidative stress to promote stone formation. Intracellular Ca2+ is an important signaling molecule, and an elevation of cytoplasmic Ca2+ levels could trigger oxidative stress. Our previous study has revealed that upregulation of Ang II/AT1R promoted renal oxidative stress during CaOx exposure. IP3/IP3R/Ca2+ signaling pathway activated via Ang II/AT1R is involved in several diseases, but its role in stone formation has not been reported. Herein, we focus on the role of AT1R/IP3/IP3R-mediated Ca2+ release in CaOx crystals-induced oxidative stress and explore whether inhibition of this pathway could alleviate renal oxidative stress. NRK-52E cells were exposed to CaOx crystals pretreated with AT1R inhibitor losartan or IP3R inhibitor 2-APB, and glyoxylic acid monohydrate-induced CaOx stone-forming rats were treated with losartan or 2-APB. The intracellular Ca2+ levels, ROS levels, oxidative stress indexes, and the gene expression of this pathway were detected. Our results showed that CaOx crystals activated AT1R to promote IP3/IP3R-mediated Ca2+ release, leading to increased cytoplasmic Ca2+ levels. The Ca2+ elevation was able to stimulate NOX2 and NOX4 to generate ROS, induce oxidative stress, and upregulate the expression of stone-related proteins. 2-APB and losartan reversed the referred effects, reduced CaOx crystals deposition and alleviated tissue injury in the rat kidneys. In summary, our results indicated that CaOx crystals promoted renal oxidative stress by activating the AT1R/IP3/IP3R/Ca2+ pathway. Inhibition of AT1R/IP3/IP3R-mediated Ca2+ release protected against CaOx crystals-induced renal oxidative stress. 2-APB and losartan might be promising preventive and therapeutic agents for the treatment of kidney stone disease.

Sharp angular and unidirectional filter based on accidental degeneracy between two twisted Weyl semimetal-based defect modes in a one-dimensional photonic crystal.

To address the challenges associated with the realization of optical non-reciprocity and enhance the efficiency of GaAs solar cells, among other systems, in this study, we investigated defect-mode interactions in a one-dimensional photonic crystal containing two Weyl semimetal-based defect layers. Moreover, two non-reciprocal defect modes were observed, namely, when defects are identical and nearby. Increasing the defect distance weakened the defect-mode interactions, thus causing the modes to gradually move closer and then degenerate into one mode. It should be noted that by changing the optical thickness of one of the defect layers, the mode was found to degrade to two non-reciprocal dots with different frequencies and angles. This phenomenon can be attributed to an accidental degeneracy of two defect modes with dispersion curves that intersect in the forward and backward directions, respectively. Moreover, by twisting Weyl semimetal layers, the accidental degeneracy occurred only in the backward direction, thus resulting in a sharp angular and unidirectional filter.

Bioinformatics analysis reveals the potential role of matrix metalloproteinases in immunity and urolithiasis.

Background: The pathogenesis of urolithiasis remains unclear, making the development of medications for treatment and prevention stagnant. Randall's plaques (RPs) begin as interstitial calcium phosphate crystal deposits, grow outward and breach the renal papillary surface, acting as attachment for CaOx stones. Since matrix metalloproteinases (MMPs) can degrade all components of extracellular matrix (ECM), they might participate in the breach of RPs. Besides, MMPs can modulate the immune response and inflammation, which were confirmed to be involved in urolithiasis. We aimed to investigate the role of MMPs in the development of RPs and stone formation. Methods: The public dataset GSE73680 was mined to identify differentially expressed MMPs (DEMMPs) between normal tissues and RPs. WGCNA and three machine learning algorithms were performed to screen the hub DEMMPs. In vitro experiments were conducted for validation. Afterwards, RPs samples were classified into clusters based on the hub DEMMPs expression. Differentially expressed genes (DEGs) between clusters were identified and functional enrichment analysis and GSEA were applied to explore the biological role of DEGs. Moreover, the immune infiltration levels between clusters were evaluated by CIBERSORT and ssGSEA. Results: Five DEMMPs, including MMP1, MMP3, MMP9, MMP10, and MMP12, were identified between normal tissues and RPs, and all of them were elevated in RPs. Based on WGCNA and three machine learning algorithms, all of five DEMMPs were regarded as hub DEMMPs. In vitro validation found the expression of hub DEMMPs also increased in renal tubular epithelial cells under lithogenic environment. RPs samples were divided into two clusters and cluster A exhibited higher expression of hub DEMMPs compared to cluster B. Functional enrichment analysis and GSEA found DEGs were enriched in immune-related functions and pathways. Moreover, increased infiltration of M1 macrophages and enhanced levels of inflammation were observed in cluster A by immune infiltration analysis. Conclusion: We assumed that MMPs might participate in RPs and stone formation through ECM degradation and macrophages-mediated immune response and inflammation. Our findings offer a novel perspective on the role of MMPs in immunity and urolithiasis for the first time, and provide potential biomarkers to develop targets for treatment and prevention.

Evaluation of the immunization effectiveness of bOPV booster immunization and IPV revaccination.

To provide a basis for further optimization of the polio sequential immunization schedule, this study evaluated the effectiveness of booster immunization with one dose of bivalent oral poliovirus vaccine (bOPV) at 48 months of age after different primary polio immunization schedules. At 48 months of age, one dose of bOPV was administered, and their poliovirus types 1-3 (PV1, PV2, and PV3, respectively)-specific neutralizing antibody levels were determined. Participants found to be negative for any type of PV-specific neutralizing antibody at 24, 36, or 48 months of age were re-vaccinated with inactivated polio vaccine (IPV). The 439 subjects who received a bOPV booster immunization at the age of 48 months had lower PV2-specific antibody levels compared with those who received IPV. One dose of IPV during basic polio immunization induced the lowest PV2-specific antibody levels. On the basis of our findings, to ensure that no less than 70% of the vaccinated have protection efficiency, we recommend the following: if basic immunization was conducted with 1IPV + 2bOPV (especially Sabin strain-based IPV), a booster immunization with IPV is recommended at 36 months of age, whereas if basic immunization was conducted with 2IPV + 1bOPV, a booster immunization with IPV is recommended at 48 months of age. A sequential immunization schedule of 2IPV + 1bOPV + 1IPV can not only maintain high levels of antibody against PV1 and PV3 but also increases immunity to PV2 and induces early intestinal mucosal immunity, with relatively good safety. Thus, this may be the best sequential immunization schedule for polio in countries or regions at high risk for polio.

Structural basis of phosphorylation-induced activation of the response regulator VbrR.

Two-component systems typically consist of a paired histidine kinase and response regulator and couple environmental changes to adaptive responses. The response regulator VbrR from Vibrio parahaemolyticus, a member of the OmpR/PhoB family, regulates virulence and antibiotic resistance genes. The activation mechanism of VbrR remains unclear. Here, we report the crystal structures of full-length VbrR in complex with DNA in the active conformation and the N-terminal receiver domain (RD) and the C-terminal DNA-binding domain (DBD) in both active and inactive conformations. Structural and biochemical analyses suggest that unphosphorylated VbrR adopts mainly as inactive dimers through the DBD at the autoinhibitory state. The RD undergoes a monomer-to-dimer transition upon phosphorylation, which further induces the transition of DBD from an autoinhibitory dimer to an active dimer and enables its binding with target DNA. Our study suggests a new model for phosphorylation-induced activation of response regulators and sheds light on the pathogenesis of V. parahaemolyticus.

Adaptive tracking control for stochastic nonlinear systems with time-varying delays using multi-dimensional Taylor network.

For stochastic nonlinear systems (SNSs) perturbed by compound uncertainties, the conventional model-based control approaches assume that the evolution behavior of uncertain variables is known. Unfortunately, such approaches are often conservative for most practical scenarios with the slow convergence speed and unsatisfactory anti-interference performance. For this sake, an adaptive control scheme based on deep deterministic policy gradient (DDPG) and multi-dimensional Taylor network (MTN) is proposed here to address the tracking problem for a category of SNSs subject to fast time-varying uncertainties, stochastic disturbance and unknown time-varying delays. The effect of time delay is embedded in the reproducing kernel Hilbert space through the error coordinate transformation. In the framework of DDPG, the MTN-based surrogate is utilized to construct the online network and target network via the temporal-difference method, which promises more desirable real-time performance due to its concise structure than conventional NN-based surrogates. In order to enhance the robustness of the system under fast time-varying uncertainties, a novel persistent excitation (PE) mechanism is designed to ensure that the control policy is appropriately rewarded or punished. Based on the PE condition, weights of MTNs converge exponentially and animate the system to evolve towards the target persistently. The tracking error and closed-loop state signals are proved theoretically to be uniformly ultimately bounded (UUB) via Lyapunov-Krasovskii functional. A numerical simulation from the process industry verifies the effectiveness of the proposed method.

The role of microbiome: a novel insight into urolithiasis.

Urolithiasis, referred to as the formation of stones in the urinary tract, is a common disease with growing prevalence and high recurrence rate worldwide. Although researchers have endeavoured to explore the mechanism of urinary stone formation for novel effective therapeutic and preventative measures, the exact aetiology and pathogenesis remain unclear. Propelled by sequencing technologies and culturomics, great advances have been made in understanding the pivotal contribution of the human microbiome to urolithiasis. Indeed, there are diverse and abundant microbes interacting with the host in the urinary tract, overturning the dogma that urinary system, and urine are sterile. The urinary microbiome of stone formers was clearly distinct from healthy individuals. Besides, dysbiosis of the intestinal microbiome appears to be involved in stone formation through the gut-kidney axis. Thus, the human microbiome has potential significant implications for the aetiology of urolithiasis, providing a novel insight into diagnostic, therapeutic, and prognostic strategies. Herein, we review and summarize the landmark microbiome studies in urolithiasis and identify therapeutic implications, challenges, and future perspectives in this rapidly evolving field. To conclude, a new front has opened with the evidence for a microbial role in stone formation, offering potential applications in the prevention, and treatment of urolithiasis.

Association between tricuspid annular systolic velocity and poor short-term prognosis in patients with acute decompensated heart failure.

BACKGROUND: There is scant data on the association of the Pulsed wave-Doppler tissue imaging (PW-DTI)-derived tricuspid lateral annular peak systolic velocity (S') and poor short-term prognosis of patients with acute decompensated heart failure (ADHF). PATIENTS AND METHODS: A total number of 732 participants from the Heb-ADHF registry in China were divided into three groups according to the corresponding status of tricuspid S'. Demographic characteristics, comorbidities, physical examinations, lab tests, and medications were compared among the different groups. Different logistic regression models were utilized to gauge the relationship between S' and the risk of a composite of short-term all-cause mortality or 30-day heart failure (HF)-related rehospitalization. RESULTS: The number of composite outcome events identified in the study population was 85, with the short-term all-cause death coupled with 30-day HF readmission events reaching 23 and 62, respectively. As per the multivariable adjusted analysis, S' was inversely related to the risk of a composite outcome [<10 cm/s odds ratios (OR) 2.90, 95% confidence interval (CI):1.33-6.31; 10-11 cm/s OR 2.18, 95% CI: 1.10-4.33; p for trend = 0.006] in comparison with S' at >11 cm/s. When S' was analysed as a continuous variable, per 1 cm/s increase, the OR (95% CI) for a composite outcome was [0.87 (0.77-0.99), p = 0.028]. Area under curve (AUC) of S' for predicting outcome of ADHF was 0.631 (95%CI: 0.573-0.690, p < 0.01). Significant inverse association was also observed in left ventricular ejection fraction (LVEF) ≥40% subgroup. CONCLUSIONS: Inspite of the potential confounders, a more impaired tricuspid annular peak systolic velocity is associated with a poorer short-term prognosis of patients with ADHF.

This is the first comprehensive evaluation of tricuspid annular systolic velocity among patients with ADHF.Tricuspid annular systolic velocity could be a predictor of poor short-term prognosis in ADHF.Tricuspid annular systolic velocity should be considered in patients with ADHF at admission.

Characterization of the Lipid Metabolism in Bladder Cancer to Guide Clinical Therapy.

Background: Bladder cancer is one of the most common malignancies of the urinary system with an unfavorable prognosis. More and more studies have suggested that lipid metabolism could influence the progression and treatment of tumors. However, there are few studies exploring the relationship between lipid metabolism and bladder cancer. This study aimed to explore the roles that lipid metabolism-related genes play in patients with bladder cancer. Methods: TCGA_BLCA cohort and GSE13507 cohort were included in this study, and transcriptional and somatic mutation profiles of 309 lipid metabolism-related genes were analyzed to discover the critical lipid metabolism-related genes in the incurrence and progression of bladder cancer. Furthermore, the TCGA_BLCA cohort was randomly divided into training set and validation set, and the GSE13507 cohort was served as an external independent validation set. We performed the LASSO regression and multivariate Cox regression in training set to develop a prognostic signature and further verified this signature in TCGA_BLCA validation set and GSE13507 external validation set. Finally, we systematically investigated the association between this signature and tumor microenvironment, drug response, and potential functions and then verified the differential expression status of signature genes in the protein level by immunohistochemistry. Results: A novel 6-lipidmetabolism-related gene signature was identified and validated, and this risk score model could predict the prognosis of patients with bladder cancer. In addition, the prognostic model was tightly related to immune cell infiltration and tumor mutation burden. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) showed that mTOR signaling pathway, G2M checkpoint, fatty acid metabolism, and hypoxia were enriched in patients in the high-risk score groups. Furthermore, 3 therapies specific for bladder cancer patients in different risk scores were identified. Conclusion: s. In conclusion, we investigated the lipid metabolism-related genes in bladder cancer through comprehensive bioinformatic analysis. A novel 6-gene signature associated with lipid metabolism for predicting the outcomes of patients with bladder cancer was conducted and validated. Furthermore, the risk score model could be utilized to indicate the choice of therapy in bladder cancer.

The renal pelvis urobiome in the unilateral kidney stone patients revealed by 2bRAD-M.

BACKGROUND: The pathogenesis of kidney stone disease (KSD) is not fully understood, and potential contributing factors remain to be explored. Several studies have revealed that the urinary microbiome (urobiome) of stone formers was distinct from that of healthy individuals using 16S rRNA gene sequencing, most of which only provided microbial identification at the genus level. 2bRAD sequencing for Microbiome (2bRAD-M) is a novel sequencing technique that enables accurate characterization of the low-biomass microbiome at the species resolution. We aimed to apply 2bRAD-M to profile the renal pelvis urobiome of unilateral kidney stone patients and compared the urobiome with and without stone(s). METHOD: A total of 30 patients with unilateral stones were recruited, and their renal pelvis urine from both sides was collected. A ureteroscope was inserted into the renal pelvis with stone(s) and a ureteral catheter was placed into the ureteroscope to collect renal pelvis urine. This procedure was repeated again with new devices to collect the urine of the other side. 2bRAD-M was performed to characterize the renal pelvis urobiome of unilateral stone formers to explore whether microbial differences existed between the stone side and the non-stone side. RESULTS: The microbial community composition of the stone side was similar to that of the non-stone side. Paired comparison showed that Corynebacterium was increased and Prevotella and Lactobacillus were decreased in the stone side. Four species (Prevotella bivia, Lactobacillus iners, Corynebacterium aurimucosum, and Pseudomonas sp_286) were overrepresented in the non-stone side. 24 differential taxa were also identified between two groups by linear discriminant analysis effect size (LEfSe). Extensive and close connections among genera and species were observed in the correlation analysis. Moreover, a random forest classifier was constructed using specific enriched species, which can distinguish the stone side from the non-stone side with an accuracy of 71.2%. CONCLUSION: This first 2bRAD-M microbiome survey gave an important hint towards the potential role of urinary dysbiosis in KSD and provided a better understanding of mechanism of stone formation.

Tumor-Targeting Ability of Novel Anti-Prostate-Specific Membrane Antigen Antibodies.

Patients with prostate-specific membrane antigen (PSMA)-positive tumors can benefit from PSMA-targeted therapy; thus, we have constructed a phage-displayed synthetic antibody library for the production of novel PSMA antibodies with superior PSMA-targeting ability, favoring clinical management. The binding affinities of anti-PSMA antibodies were verified by an enzyme-linked immunosorbent assay (ELISA). Several in vitro and in vivo experiments, including cellular uptake, internalization, and cytotoxicity studies, micro single photon emission computed tomography (microSPECT)/CT, and biodistribution studies, were performed to select the most promising antibody among six different antibodies. The results showed the target affinities of our antibodies in the ELISA assays (7A, 8C, 8E, and 11A) were comparable to the existing antibodies (J591). The half-maximal effective concentrations of 7A, 8C, 8E, 11A, and J591 were 2.95, 6.64, 5.50, 2.08, and 4.79, respectively. The radiochemical yield of 111In-labeled antibodies ranged from 30% to 50% with high radiochemical purity (>90%). In the cellular uptake studies, the accumulated radioactivity of 111In-J591, 111In-7A, and 111In-11A increased over time. The internalized percentage of 111In-11A was the highest (32.14% ± 2.06%) at 48 h after incubation, whereas that of 111In-J591 peaked at 22.43% ± 4.38% at 24 h and dropped to 13.52% ± 3.03% at 48 h postincubation. Twenty-four hours after injection, radioactivity accumulation appeared in the LNCaP xenografts of the mice injected with 111In-11A, 111In-8E, 111In-7A, and 111In-J591 but not in the xenografts of the 111In-8C-injected group. Marked liver uptake was noticed in all groups except the 111In-11A-injected group. Moreover, the killing effect of 177Lu-11A was superior to that of 177Lu-J591 at low concentrations. In conclusion, we successfully demonstrated that 11A IgG owned the most optimal biological characteristics among several new anti-PSMA antibodies and it can be an excellent PSMA-targeting component for the clinical use.

Validation and derivation of short-term prognostic risk score in acute decompensated heart failure in China.

BACKGROUND: Few prognostic risk scores (PRSs) have been routinely used in acute decompensated heart failure (ADHF). We, therefore, externally validated three published PRSs (3A3B, AHEAD, and OPTIME-CHF) and derived a new PRS to predict the short-term prognosis in ADHF. METHODS: A total of 4550 patients from the Heb-ADHF registry in China were randomly divided into the derivation and validation cohorts (3:2). Discrimination of each PRS was assessed by the area under the receiver operating characteristic curve (AUROC). Logistic regression was exploited to select the predictors and create the new PRS. The Hosmer-Lemeshow goodness-of-fit test was used to assess the calibration of the new PRS. RESULTS: The AUROCs of the 3A3B, AHEAD, and OPTIME-CHF score in the derivation cohort were 0.55 (95% CI 0.53-0.57), 0.54 (95% CI 0.53-0.56), and 0.56 (95% CI 0.54-0.57), respectively. After logistic regression analysis, the new PRS computed as 1 × (diastolic blood pressure < 80 mmHg) + 2 × (lymphocyte > 1.11 × 109/L) + 1 × (creatinine > 80 µmol/L) + 2 × (blood urea nitrogen > 21 mg/dL) + 1 × [BNP 500 to < 1500 pg/mL (NT-proBNP 2500 to < 7500 pg/mL)] or 3 × [BNP ≥ 1500 (NT-proBNP ≥ 7500) pg/mL] + 3 × (QRS fraction of electrocardiogram < 55%) + 4 × (ACEI/ARB not used) + 1 × (rhBNP used), with a better AUROC of 0.67 (95% CI 0.64-0.70) and a good calibration (Hosmer-Lemeshow χ2 = 3.366, P = 0.186). The results in validation cohort verified these findings. CONCLUSIONS: The short-term prognostic values of 3A3B, AHEAD, and OPTIME-CHF score in ADHF patients were all poor, while the new PRS exhibited potential predictive ability. We demonstrated the QRS fraction of electrocardiogram as a novel predictor for the short-term outcomes of ADHF for the first time. Our findings might help to recognize high-risk ADHF patients.

Early Warning of Enterprise Financial Risk Based on Decision Tree Algorithm.

To improve enterprise financial early warning, we propose an algorithm based on a decision tree. According to the shortcomings and defects of the classical algorithm and the traditional decision tree algorithm, in the ordinary decision tree improved algorithm based on PCA, there is a problem that the representativeness of the data after dimensionality reduction processing are not high, resulting in the fact that the accuracy of the algorithm can be improved slightly after multiple data runs. Based on the classical algorithm, attribute eigenvalues before classification are extracted twice, and the amount of data to be classified is calculated. That is, the most important attributes of the original data are selected. After the subtree is established, the dimension reduction and merging selection of the data are performed, and the improved algorithm is verified by using three data sets in the UCI database. The results show that the average accuracy in the three datasets is 94.6%, which is improved by 1.6% and 0.6% for the traditional classical algorithm and the ordinary PCA decision tree optimization algorithm, respectively. PCA-based decision tree algorithms can improve the accuracy of the results to some extent, which is of practical importance. In the future, a classic algorithm improved for secondary modeling will be used to obtain a more efficient decision tree model. The decision tree algorithm has been proven to recognize an early warning of an enterprise's financial risks, which enhances the effectiveness of an enterprise's early financial warning.

MYC-Induced Upregulation of Lncrna ELFN1-AS1 Contributes to Tumor Growth in Colorectal Cancer via Epigenetically Silencing TPM1.

Recently, long noncoding RNAs (lncRNA) have been reported as tumor suppressors or oncogenes in colorectal cancer. This study aims to discover functional role of a novel lncRNA in colorectal cancer tumorigenesis. Expression profile of fibronectin type III domain containing 1 antisense RNA 1 (ELFN1-AS1) in colorectal cancer samples was displayed on TCGA database. Expression level of ELFN1-AS1 was tested in colorectal cancer tissues and cell lines via qRT-PCR. Functional role of ELFN1-AS1 was assessed by loss-of-function assays. Mechanism experiments, such as chromatin immunoprecipitation (ChIP) assay and luciferase reporter assay, were done to analyze the molecular mechanism of ELFN1-AS1 in colorectal cancer. ELFN1-AS1 knockdown inhibited colorectal cancer tumor growth through restricting cell proliferation and facilitating cell apoptosis. ELFN1-AS1 was transcriptionally activated by MYC. Moreover, ELFN1-AS1 led to transcriptional silencing of tropomyosin 1 (TPM1) via recruiting enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) and forkhead box P1 (FOXP1). Collectively, MYC-upregulated ELFN1-AS1 recruited EZH2 and FOXP1 to restrain TPM1 expression, thereby promoting colorectal cancer tumor growth. IMPLICATIONS: This study revealed a novel molecular pathway in colorectal cancer progression, which may provide new method for early diagnosis and treatment of colorectal cancer.

Application Value of Machine Learning Method in Measuring Gray Matter Volume of AIDS Patients.

Background: To investigate the role of gray matter (GM) volume in the identification of HIV-positive patients with HIV-associated neurocognitive impairment (HAND) using a machine learning approach from normal healthy controls. Methods: Twenty-seven HIV-infected patients and 14 healthy controls were enrolled in our study. Each set of BRAVO images was postprocessed using DPARSF3.1 to coregister all brains on the MNI template, and volume extraction of 90 brain regions was performed using custom-designed code. The machine learning method was performed using PRoNTo2.1.1 toolbox. The differences in brain volume between the HAND and non-HAND groups were analyzed. Results: GM volume effectively distinguished HIV-positive patients from healthy subjects with an AUC equals to 0.73. The sensitivity, specificity, and accuracy of the established classification were 85.19%, 42.86%, and 70.73%, respectively. GM volume value of the top ten brain regions was related to digit symbols, trail making test, digit span, vocabulary fluency, stroop C time, stroop CW time, CD4, and neuropsychological group. Conclusions: A machine learning approach facilitates early diagnosis of HAND in HIV patients by MRI-based GM volume measurement.