The diagnostic role of resting myocardial blood flow in STEMI patients after revascularization.

Background: The value of semiquantitative resting myocardial perfusion imaging (MPI) in coronary artery disease (CAD) is limited. At present, quantitative MPI can be performed by a new cadmium zinc tellurium single-photon emission computed tomography (CZT-SPECT) scan. The quantitative index of resting myocardial blood flow (MBF) has received little attention, and its manifestations and clinical value in the presence of unstable coronary blood flow have not been clarified. Purpose: In patients with ST-segment elevation myocardial infarction (STEMI), whether resting MBF can provide additional value of blood flow than semi-quantitative resting MPI is not sure. We also explored the influencing factors of resting MBF. Methods: This was a retrospective clinical study. We included 75 patients with STEMI in the subacute phase who underwent resting MPI and dynamic scans after reperfusion therapy. General patient information, STEMI-related data, MPI, gated MPI (G-MPI), and resting MBF data were collected and recorded. According to the clinically provided culprit vessels, the resting MBF was divided into ischemic MBF and non-ischemic MBF. The paired Wilcoxon signed-rank test was used for resting MBF. The receiver operating characteristic (ROC) curves were used to determine the optimal threshold for ischemia, and multiple linear regression analysis was used to analyze the influencing factors of resting MBF. Results: There was a statistically significant difference between the ischemic MBF and non-ischemic MBF [0.59 (0.47-0.72) vs. 0.76 (0.64-0.93), p < 0.0001]. The ROC curve analysis revealed that resting MBF could identify ischemia to a certain extent, with a cutoff value of 0.5975, area under the curve (AUC) = 0.666, sensitivity = 55.8%, and specificity = 68.7%. Male sex and summed rest score (SRS) were influencing factors for resting MBF. Conclusion: To a certain extent, resting MBF can suggest residual ischemia after reperfusion therapy in patients with STEMI. There was a negative correlation between male sex, SRS, and ischemic MBF. A lower resting MBF may be associated with more severe myocardial ischemia.

Machine learning predictor PSPire screens for phase-separating proteins lacking intrinsically disordered regions.

The burgeoning comprehension of protein phase separation (PS) has ushered in a wealth of bioinformatics tools for the prediction of phase-separating proteins (PSPs). These tools often skew towards PSPs with a high content of intrinsically disordered regions (IDRs), thus frequently undervaluing potential PSPs without IDRs. Nonetheless, PS is not only steered by IDRs but also by the structured modular domains and interactions that aren't necessarily reflected in amino acid sequences. In this work, we introduce PSPire, a machine learning predictor that incorporates both residue-level and structure-level features for the precise prediction of PSPs. Compared to current PSP predictors, PSPire shows a notable improvement in identifying PSPs without IDRs, which underscores the crucial role of non-IDR, structure-based characteristics in multivalent interactions throughout the PS process. Additionally, our biological validation experiments substantiate the predictive capacity of PSPire, with 9 out of 11 chosen candidate PSPs confirmed to form condensates within cells.

Tungsten-Iron-Ruthenium Ternary Alloy Immobilized into the Inner Nickel Foam for High-Current-Density Water Oxidation.

The pursuit of highly-active and stable catalysts in anodic oxygen evolution reaction (OER) is desirable for high-current-density water electrolysis toward industrial hydrogen production. Herein, a straightforward yet feasible method to prepare WFeRu ternary alloying catalyst on nickel foam is demonstrated, whereby the foreign W, Fe, and Ru metal atoms diffuse into the Ni foam resulting in the formation of inner immobilized ternary alloy. Thanks to the synergistic impact of foreign metal atoms and structural robustness of inner immobilized alloying catalyst, the well-designed WFeRu@NF self-standing anode exhibits superior OER activities. It only requires overpotentials of 245 and 346 mV to attain current densities of 20 and 500 mA cm-2 , respectively. Moreover, the as-prepared ternary alloying catalyst also exhibits a long-term stability at a high-current-density of 500 mA cm-2 for over 45 h, evidencing the inner-immobilization strategy is promising for the development of highly active and stable metal-based catalysts for high-density-current water oxidation process.

Correlation between IL3 signaling pathway-related genes and immune checkpoint inhibitor efficacy in patients with renal cell carcinoma.

BACKGROUND: There is a lack of effective biomarkers that predict immunotherapy efficacy in clear cell renal cell carcinoma(KIRC). OBJECTIVE: We aimed to identify biomarkers that would predict the efficacy of KIRC treatment with immune checkpoint inhibitors (ICIs). METHODS: Cohort data of KIRC patients with somatic mutations, mRNA expression and survival data from The Cancer Genome Atlas (TCGA) database and immunotherapy cohort and Genomics of Drug Sensitivity in Cancer (GDSC) database were analyzed and divided into interleukin 3 (IL3) pathway-related genes high expression (IL3-High) and IL3 pathway-related genes low expression (IL3-Low) groups according to pathway expression status to assess the relationship between the IL3 pathway-related genes activation status and the prognosis of KIRC patients treated with ICIs. The data were validated by immunohistochemistry experiments, and possible mechanisms of action were explored at the level of gene mutation landscape, immune microenvironment characteristics, transcriptome and copy number variation(CNV) characteristicsRESULTS: The IL3 pathway-related genes was an independent predictor of the efficacy of ICIs in KIRC patients, and the IL3-High group had a longer overall survival (OS); KIRC patients in the IL3-High group had increased levels of chemokines, cytolysis, immune checkpoint gene expression and abundant immunity. The IL3-Low group had poor immune cell infiltration and significant downregulation of complement activation, cytophagy, B-cell activation, and humoral immune response pathways. The high group was more sensitive to targeted drugs of some signaling pathways, and its efficacy in combining these drugs with immunity has been predicted in the published literature. CONCLUSION: The IL3 pathway-related genes can be used as a predictor of the efficacy of ICIs in KIRC. The IL3 pathway-related genes may affect the therapeutic efficacy of ICIs by affecting the expression of immune-related molecules, immune cell infiltration, and the level of immune response pathways.

Comprehensive Analysis Identifies PKP3 Overexpression in Pancreatic Cancer Related to Unfavorable Prognosis.

Plakophilin 3 (PKP3) affects cell signal transduction and cell adhesion and performs a crucial function in tumorigenesis. The current investigation evaluated the predictive significance and underlying processes of PKP3 within pancreatic cancer (PC) tissues. The assessment of differences in PKP3 expression was conducted through an analysis of RNA-seq data acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Additionally, clinical samples were collected to validate the findings. The predictive significance of PKP3 was investigated by analyzing survival data derived from TCGA and clinical specimens. PKP3's biological function was assessed via phenotypic experiments after the suppression of PKP3 expression within PC cells. Functional enrichment analysis, encompassing KEGG, GO, and GSEA, was employed to assess the underlying mechanism of PKP3. Immune infiltration analysis was conducted in the present investigation to determine the association between PKP3 and tumor-infiltrating immune cells (TICs). In PC tissues, PKP3 expression was abnormally upregulated and correlated with a negative prognosis in individuals with PC. PKP3 can promote the progression, migration, and invasive capacity of PC cells and is relevant to the regulation of the PI3K-Akt and MAPK signaling pathways. Immune infiltration analysis demonstrated that PKP3 impeded CD8+ T-cell infiltration and immune cytokine expression within the tumor microenvironment. The PKP3 protein was identified as a prospective independent predictive indicator and represents a viable approach for immunotherapy in the context of PC. PKP3 may impact prognosis by broadly inhibiting immune cell infiltration and promoting the activation of tumor-associated signaling pathways.

Metallic W/WO2 solid-acid catalyst boosts hydrogen evolution reaction in alkaline electrolyte.

The lack of available protons severely lowers the activity of alkaline hydrogen evolution reaction process than that in acids, which can be efficiently accelerated by tuning the coverage and chemical environment of protons on catalyst surface. However, the cycling of active sites by proton transfer is largely dependent on the utilization of noble metal catalysts because of the appealing electronic interaction between noble metal atoms and protons. Herein, an all-non-noble W/WO2 metallic heterostructure serving as an efficient solid-acid catalyst exhibits remarkable hydrogen evolution reaction performance with an ultra-low overpotential of -35 mV at -10 mA/cm2 and a small Tafel slope (-34 mV/dec), as well as long-term durability of hydrogen production (>50 h) at current densities of -10 and -50 mA/cm2 in alkaline electrolyte. Multiple in situ and ex situ spectroscopy characterizations combining with first-principle density functional theory calculations discover that a dynamic proton-concentrated surface can be constructed on W/WO2 solid-acid catalyst under ultra-low overpotentials, which enables W/WO2 catalyzing alkaline hydrogen production to follow a kinetically fast Volmer-Tafel pathway with two neighboring protons recombining into a hydrogen molecule. Our strategy of solid-acid catalyst and utilization of multiple spectroscopy characterizations may provide an interesting route for designing advanced all-non-noble catalytic system towards boosting hydrogen evolution reaction performance in alkaline electrolyte.

CACNA1C mutation as a prognosis predictor of immune checkpoint inhibitor in skin cutaneous melanoma.

Aims: There is an urgent need for appropriate biomarkers that can precisely and reliably predict immunotherapy efficacy, as immunotherapy responses can differ in skin cutaneous melanoma (SKCM) patients. Methods: In this study, univariate regression models and survival analysis were used to examine the link between calcium voltage-gated channel subunit alpha 1C (CACNA1C) mutation status and immunotherapy outcome in SKCM patients receiving immunotherapy. Mutational landscape, immunogenicity, tumor microenvironment and pathway-enrichment analyses were also performed. Results: The CACNA1C mutation group had a better prognosis, higher immunogenicity, lower endothelial cell infiltration, significant enrichment of antitumor immune response pathways and significant downregulation of protumor pathways. Conclusion: CACNA1C mutation status is anticipated to be a biomarker for predicting melanoma immunotherapy effectiveness.

Aims: The treatment to make the immune system work better is also used to treat a skin cancer called skin cutaneous melanoma (SKCM). We need new ways to predict if the treatment will work. Methods: We looked at two groups of people getting the treatment to make the immune system work better. One group had a special change in their bodies, and the other group did not. We looked at how this change affected the patients. We also looked at how to make their immune system stronger. Results: We found that people with mutations tend to have better chances of getting better from their sickness. Conclusion: We think that this might be a good way to tell if immunotherapy will work well for this type of SKCM.

Assessing community assembly controls over community-scale nutrient resorption responses to nitrogen deposition.

Nutrient resorption is a fundamental physiological process in plants, with important ecological controls over numerous ecosystem functions. However, the role of community assembly in driving responses of nutrient resorption to perturbation remains largely unknown. Following the Price equation framework and the Community Assembly and Ecosystem Function framework, we quantified the contribution of species loss, species gain, and shared species to the reduction of community-level nutrient resorption efficiency in response to multi-level nitrogen (N) addition in a temperate steppe, after continuous N addition for seven years. Reductions of both N and phosphorus (P) resorption efficiency (NRE and PRE, respectively) were positively correlated with N addition levels. The dissimilarities in species composition between N-enriched and control communities increased with N addition levels, and N-enriched plots showed substantial species losses and gains. Interestingly, the reduction of community-scale NRE and PRE mostly resulted from N-induced decreases in resorption efficiency for the shared species in the control and N-enriched communities. There were negative correlations between the contributions of species richness effect and species identity effect and between the number and identity of species gained for the changes in both NRE and PRE following N enrichment. By simultaneously considering N-induced changes in species composition and in species-level resorption, our work presents a more complete picture of how different community assembly processes contribute to N-induced changes in community-level resorption.

Neuroplastin 65 deficiency reduces amyloid plaque formation and cognitive deficits in an Alzheimer's disease mouse model.

Introduction: Alzheimer's disease (AD) is characterized by increasing cognitive dysfunction, progressive cerebral amyloid beta (Aß) deposition, and neurofibrillary tangle aggregation. However, the molecular mechanisms of AD pathologies have not been completely understood. As synaptic glycoprotein neuroplastin 65 (NP65) is related with synaptic plasticity and complex molecular events underlying learning and memory, we hypothesized that NP65 would be involved in cognitive dysfunction and Aß plaque formation of AD. For this purpose, we examined the role of NP65 in the transgenic amyloid precursor protein (APP)/presenilin 1 (PS1) mouse model of AD. Methods: Neuroplastin 65-knockout (NP65-/-) mice crossed with APP/PS1 mice to get the NP65-deficient APP/PS1 mice. In the present study, a separate cohort of NP65-deficient APP/PS1 mice were used. First, the cognitive behaviors of NP65-deficient APP/PS1 mice were assessed. Then, Aß plaque burden and Aß levels in NP65-deficient APP/PS1 mice were measured by immunostaining and western blot as well as ELISA. Thirdly, immunostaining and western blot were used to evaluate the glial response and neuroinflammation. Finally, protein levels of 5-hydroxytryptamin (serotonin) receptor 3A and synaptic proteins and neurons were measured. Results: We found that loss of NP65 alleviated the cognitive deficits of APP/PS1 mice. In addition, Aß plaque burden and Aß levels were significantly reduced in NP65-deficient APP/PS1 mice compared with control animals. NP65-loss in APP/PS1 mice resulted in a decrease in glial activation and the levels of pro- and anti-inflammatory cytokines (IL-1ß, TNF-α, and IL-4) as well as protective matrix YM-1 and Arg-1, but had no effect on microglial phenotype. Moreover, NP65 deficiency significantly reversed the increase in 5-hydroxytryptamine (serotonin) receptor 3A (Htr3A) expression levels in the hippocampus of APP/PS1 mice. Discussion: These findings identify a previously unrecognized role of NP65 in cognitive deficits and Aß formation of APP/PS1 mice, and suggest that NP65 may serve as a potential therapeutic target for AD.

Trends in care quality in China from 2011 to 2017: An analysis based on the National Specific (Single) Disease Monitoring System.

Background: The Ministry of Health of China conducted a study targeting in single-disease quality control in 2009, aimed to strengthen quality management and improve health care services. This study retrospectively investigated the trends of quality indicators for six monitored diseases 2011-2017 to evaluate the improvement of care quality for the first batch of single-disease. Methods: We extracted data from the National Specific (Single) Disease Monitoring System for 2011-2017. We focused on six conditions: acute myocardial infarction, heart failure, community-acquired pneumonia, coronary artery bypass graft, hip / knee replacement, and acute ischemic stroke. A total of 56 quality indicators (QIs) were adopted to monitor the quality change and determine the trends in care quality. We also calculated the hospital process composite performance (HPCP) using a denominator-based weighting method for each hospital per year. The estimated annual percentage changes (EAPC) 2011-2017 were calculated at national and regional levels. Results: The results showed that use of four QIs had significant downward trends, whereas 25 QIs (including reversed indicators) showed significant upward trends from 2011 to 2017. The greatest improvement was observed in CAP-4 (antibiotic treatment within four hours after admission to the hospital for critical pneumonia) in the central region (EAPC = 48.36, 95% CI = 15.92-89.87); while the largest decrease appeared in AIS-1 (thrombolytic therapy within 4.5 hours of symptom onset) in the western region (EAPC = -13.44, 95% CI = -24.98,-0.11). An increased HPCP was observed in four diseases nationwide, but not for acute myocardial infarction and heart failure. However, there were significant differences across regions in the process of care and outcomes, with the performance of Eastern and Western regions showing remarkable advantages compared with the Central region. Conclusions: We provide evidence for major advancement in care quality in China nationwide. However, the improvement of care in China was unbalanced geographically and should be carefully considered. Future challenges include expanding the coverage of quality monitoring, greater delivery efficiency, and region-balanced health care.

Ga2O3 Quantum Dots with N-Doped Amorphous Carbon Fixed for Efficient Storage and Transfer of Lithium Ions by Introduction of Dopamine Hydrochloride.

The Ga2O3 anode has great potential due to its self-healing and high theoretical capacity in lithium-ion batteries. Like anodes with other transition metal oxides, the Ga2O3 anode has the problems of structural change and low electrical conductivity. The electrochemical performance of the Ga2O3 anode still needs to be improved. In this work, we synthesized a Ga2O3 quantum dots@N-doped carbon (Ga2O3-QD@NC) composite by hydrothermal reaction with a carbon source of dopamine hydrochloride, in which Ga2O3 quantum dots were dispersed in the interior of the amorphous carbon. Such a special structure is conducive to the high-speed migration of lithium ions and electrons and effectively inhibits volume expansion and agglomeration. Smaller and more uniform quantum dots facilitate efficient repair of the structure. Due to these advantages, the Ga2O3-QD@NC electrode has great electrochemical performance. The Ga2O3-QD@NC electrode has an initial discharge capacity of 1580 mAh g-1 with a high first Coulombic efficiency of 62.8% and a cycling capacity of 953 mAh g-1 under 0.1 A g-1. It even has a capacity of 460 mAh g-1 at 1 A g-1 after 300 cycles. This strategy can provide a new direction for the Ga2O3 anode in lithium-ion batteries with high capacity.

A Novel Cuproptosis-Associated Gene Signature to Predict Prognosis in Patients with Pancreatic Cancer.

Background: Pancreatic cancer (PAAD) is a malignant tumor with a poor prognosis and lacks sensitive biomarkers for diagnosis and targeted therapy. Cuproptosis, a recently proposed form of cell death based on cellular copper ion concentration, plays a key role in cancer biology. This study is aimed at constructing a risk model for predicting the prognosis of PAAD patients based on cuproptosis-related genes. Methods: Pancreatic-related data from UCSC-TCGA and UCSC-GTEx databases were extracted for analysis, and TCGA-PAAD samples were randomly divided into the training and validation groups. Pearson correlation analysis was used to obtain cuproptosis-related genes coexpressed with 19 copper death genes. Univariate Cox and Lasso regression analyses were used to obtain cuproptosis-related prognostic genes. Multivariate Cox regression analysis was used to construct the final prognostic risk model. The risk score curve, Kaplan-Meier survival curves, and ROC curve were used to evaluate the predictive ability of the Cox risk model. Finally, the functional annotation of the risk model was obtained through enrichment analysis. Results: The Cox risk model has an eight prognostic cuproptosis-related gene signature. Kaplan-Meier survival curves demonstrated that the high-risk group had a shorter survival time. The ROC curve of the risk score was well created to predict one-, three-, and five-year survival rates, and AUC of the risk score was higher than other clinical characteristics. Cox regression analysis revealed that the risk score has an independent prognostic value for PAAD. GSEA reveals specific tumor pathways associated with the risk model (Myc targets v1, mTORC1 signaling, and E2F targets). Conclusions: We constructed a prognostic model containing eight cuproptosis-related genes (AKR1B10, KLHL29, PROM2, PIP5K1C, KIF18B, AMIGO2, MRPL3, and PI4KB) that can accurately predict the prognosis of PAAD patients. The results will provide new perspectives for individualized outcome prediction and new therapy development for PAAD patients.

The quality disparity of stroke care over time: An analysis based on the national dataset from 2011 to 2017.

BACKGROUND: Adherence to evidence-based hospital stroke care is variable and may change over time. It is important to determine which process measures are associated with variation in outcome. In a large dataset, we analyzed the association between process and outcome and the fluctuations of indicators over time, and identified quality indicators (QIs) that should be prioritized for improving the quality of stroke care. METHODS: We analyzed data from 123,259 patients diagnosed with acute ischemic stroke (AIS) who were treated at 109 large tertiary hospitals in China between January 2011 and May 2017. In total, 12 stroke treatment indicators were selected to calculate the hospital process composite performance (HPCP). Hospitals were divided into subgroups according to the time trend of HPCP estimated by the Group-Based Model. We analyzed the influence of hospital subgroups on the patient outcomes using a multi-level model and explored the QIs that led to variation. RESULTS: The HPCP trends for stroke indicators of 109 hospitals over 7 years were divided into two groups (Group 1, low-HPCP; Group 2, high-HPCP). After adjusting for patient age, medical insurance, comorbidities, patterns of admission, and NIHSS-scores, patients in the high-HPCP group presented higher rate of independence and longer length of stay compared to the low-HPCP group. The multi-level model showed that there was a statistically significant difference in the utilization rate between the two groups, with most marked differences seen in emergency assessment and function evaluation indicators. CONCLUSION: Variation in the quality of stroke care exists across hospitals, and better adherence to guideline-based care is associated with improved outcomes. We found that QIs related to emergency examination and functional assessment were the main factors differing between good and poor adherers to stroke indicators, suggesting that quality improvement in stroke care could prioritize these QIs.

Clinical characteristics and prognostic nomogram for patients with insular thyroid carcinoma: a population-based analysis.

BACKGROUND: Insular thyroid carcinoma (ITC) is an uncommon poorly differentiated thyroid malignancy. Due to its rarity, its demographic and clinicopathological features and survival remains unclear. The present study aimed to describe the features and survival of ITC, determine its prognostic factors, and establish a prognostic nomogram. METHODS: Patients with ITC were identified in the Surveillance, Epidemiology, and End Results database from 2004 to 2019. The features and survival of patients with ITC and other thyroid carcinomas were compared after balancing the baseline characteristics using propensity score matching (PSM). Univariate and multivariate Cox analyses were used to identify the prognostic factors for ITC. Moreover, overall survival (OS)- or cancer-specific survival (CSS)-specific nomograms were established to predict ITC prognosis. RESULTS: A total of 206 patients with ITCs were identified. The 1-, 2-, 5-, and 10-year OS rates of 206 patients with ITC were 90.3%, 82.0%, 62.2%, and 42.5%, respectively. The median OS was 93 months (95% CI, 73.0-140.0), while the median CSS was 141 months (95% CI, 93.0-173.0). After PSM analysis, the survival analysis of the matched cohort revealed that ITC had a worse clinical outcome than papillary thyroid cancer and follicular thyroid cancer, and better survival than anaplastic thyroid carcinoma. Multivariate Cox regression analysis demonstrated that age, N stage, M stage, and surgery were independent prognostic factors for both OS and CSS in ITC patients. The C-indices for the OS- and CSS-specific nomograms were 0.778 (95% CI, 0.724-0.832) and 0.808 (95% CI, 0.754-0.862), respectively. The calibration curve and ROC analysis indicated that the nomogram models exhibited a good discriminative ability. Decision curve analysis suggested that the nomogram models had a significant positive net benefit and were better than the traditional TNM staging system at predicting survival. CONCLUSION: ITC has distinct clinicopathological characteristics and survival compared to other thyroid carcinomas, and the established nomogram could predict the survival probability of patients with ITC accurately with a higher net benefit.

Evaluation of poly(N-isopropylacrylamide)/tetraphenylethylene/amphotericin B-based visualized antimicrobial nanofiber wound dressing for whole skin wound healing in rats.

The aim of this work is to develop a novel nanofiber wound dressing with multiple functional properties that combines suitable mechanical properties, slow and controlled drug release, antifungal activity, and visual drug monitoring to accelerate wound healing while reducing systemic circulation of the drug, achieving reduced dose and side effects, and achieving patient satisfaction and compliance. In this paper, visualized nanofiber films were prepared using electrostatic spinning technology. This nanofiber wound dressing has soft tissue-like mechanical and antifungal properties and is biocompatible. In particular, the poly(N-isopropylacrylamide) (PNIPAAm)/tetraphenylethylene (TPE)/amphotericin B (AMB) nanofiber films showed good performance in terms of antifungal activity and cytocompatibility compared with medical gauze, and significantly accelerated the wound healing process in a mouse total wound defect model with PCL+PVP+TPE+AMB+PNIPAAm. The wound healing rate of nanofibrous membrane group was 100% at 14 days. In addition, histological analysis, collagen deposition and immunohistochemistry showed, for example, fewer inflammatory cells, more fibroblasts around the damaged area, increased wound epithelial atrophy, reduced granulation tissue, connective tissue reconstruction, epithelial tissue formation, and abundant small angiogenesis in the dermis near the epidermis; a higher level of collagen deposition fraction of 49.97%; and a simultaneous reduction in HIF-1α production and upregulated the expression of CD31. In conclusion, this antifungal nanofiber film showed promising applications throughout the skin wound healing process.

A Selective Fluorescent l-Lactate Biosensor Based on an l-Lactate-Specific Transcription Regulator and Förster Resonance Energy Transfer.

Selective detection of l-lactate levels in foods, clinical, and bacterial fermentation samples has drawn intensive attention. Many fluorescent biosensors based on non-stereoselective recognition elements have been developed for lactate detection. Herein, the allosteric transcription factor STLldR from Salmonella enterica serovar Typhimurium LT2 was identified to be stereo-selectively respond to l-lactate. Then, STLldR was combined with Förster resonance energy transfer (FRET) to construct a fluorescent l-lactate biosensor FILLac. FILLac was further optimized by truncating the N- and C-terminal amino acids of STLldR between cyan and yellow fluorescent proteins. The optimized biosensor FILLac10N0C exhibited a maximum emission ratio change (ΔRmax) of 33.47 ± 1.91%, an apparent dissociation constant (Kd) of 6.33 ± 0.79 µM, and a limit of detection of 0.68 µM. FILLac10N0C was applied in 96-well microplates to detect l-lactate in bacterial fermentation samples and commercial foods such as Jiaosu and yogurt. The quantitation results of FILLac10N0C exhibited good agreement with that of a commercial l-lactate biosensor SBA-40D bioanalyzer. Thus, the biosensor FILLac10N0C compatible with high-throughput detection may be a potential choice for quantitation of l-lactate in different biological samples.

The role of Kimmelstiel-Wilson nodule in the kidney outcome in patients with diabetic kidney disease: A two-center retrospective cohort study.

AIMS: In the current study, we aimed to investigate the predictive value of the Kimmelstiel-Wilson (K-W) nodule for the risk of ESKD in patients with type 2 diabetes mellitus (T2DM). METHODS: In the two-center retrospective study, clinical and pathological parameters were compared between DKD patients with and without K-W nodules. Furthermore, we used Cox regression analysis to explore the predictive value of the K-W nodule for the risk of ESKD. RESULTS: Compared with DKD patients without K-W nodules, patients with K-W nodules had a significantly higher level of proteinuria [5.1(3.1, 8.0) g/24 hr vs. 2.4(1.1, 4.4) g/24 hr, p < 0.001]. Patients with K-W nodules had significantly higher interstitial fibrosis and tubular atrophy (IFTA) and arteriosclerosis scores than those without (p = 0.001 and p = 0.006). Kaplan-Meier analysis showed that the probability of developing ESKD was significantly higher in patients with K-W nodules than in those without (log-rank test, p < 0.001). However, after adjusting closer variables, the K-W nodule was not an independent predictor for the risk of ESKD (p > 0.05). CONCLUSIONS: In T2DM patients with DKD, the K-W nodule was associated with a more severe phenotype, and to some extent, associated with poorer renal outcome, but might not be an independent risk factor for the progression of ESKD.

Epithelial-Mesenchymal Transition-Based Gene Signature and Distinct Molecular Subtypes for Predicting Clinical Outcomes in Breast Cancer.

Purpose: Regulation of inducers and transcription factor families influence epithelial-mesenchymal transition (EMT), a contributing factor to breast cancer invasion and progression. Methods: Molecular subtypes were classified based on EMT-related mRNAs using ConsensusClusterPlus package. Differences in tumor immune microenvironment and prognosis were assessed among subtypes. Based on EMT genes, a gene signature for prognosis was built using TCGA training set by performing multivariate and univariate Cox regression analyses. Prediction accuracy of the signature was validated by receiver operating characteristic (ROC) curves and overall survival analysis on internal and external datasets. By conducting univariate and multivariate Cox regression analyses, the risk signature as an independent prognostic indicator was assessed. A nomogram was constructed and validated by calibration analysis and decision curve analysis (DCA). Results: Five molecular subtypes were characterized based on EMT genes. Patients in Cluster 2 exhibited an activated immune state and a better prognosis. An 11-EMT gene-signature was built to predict breast cancer prognosis. After validation, the signature showed independence and robustness in predicting clinical outcomes of patients. A nomogram combining the RiskScore and pTNM_stage accurately predicted 1-, 2-, 3-, and 5-year survival chance. In comparison with published model, the current model showed a higher area under the curve (AUC). Conclusion: We characterized five breast cancer subtypes with distinct clinical outcomes and immune status. The study developed an 11-EMT gene-signature as an independent prognostic factor for predicting clinical outcomes of breast cancer.