Targeting JMJD1C to selectively disrupt tumor Treg cell fitness enhances antitumor immunity.

Regulatory T (Treg) cells are critical for immune tolerance but also form a barrier to antitumor immunity. As therapeutic strategies involving Treg cell depletion are limited by concurrent autoimmune disorders, identification of intratumoral Treg cell-specific regulatory mechanisms is needed for selective targeting. Epigenetic modulators can be targeted with small compounds, but intratumoral Treg cell-specific epigenetic regulators have been unexplored. Here, we show that JMJD1C, a histone demethylase upregulated by cytokines in the tumor microenvironment, is essential for tumor Treg cell fitness but dispensable for systemic immune homeostasis. JMJD1C deletion enhanced AKT signals in a manner dependent on histone H3 lysine 9 dimethylation (H3K9me2) demethylase and STAT3 signals independently of H3K9me2 demethylase, leading to robust interferon-γ production and tumor Treg cell fragility. We have also developed an oral JMJD1C inhibitor that suppresses tumor growth by targeting intratumoral Treg cells. Overall, this study identifies JMJD1C as an epigenetic hub that can integrate signals to establish tumor Treg cell fitness, and we present a specific JMJD1C inhibitor that can target tumor Treg cells without affecting systemic immune homeostasis.

Unlocking the potential: machine learning applications in electrocatalyst design for electrochemical hydrogen energy transformation.

Machine learning (ML) is rapidly emerging as a pivotal tool in the hydrogen energy industry for the creation and optimization of electrocatalysts, which enhance key electrochemical reactions like the hydrogen evolution reaction (HER), the oxygen evolution reaction (OER), the hydrogen oxidation reaction (HOR), and the oxygen reduction reaction (ORR). This comprehensive review demonstrates how cutting-edge ML techniques are being leveraged in electrocatalyst design to overcome the time-consuming limitations of traditional approaches. ML methods, using experimental data from high-throughput experiments and computational data from simulations such as density functional theory (DFT), readily identify complex correlations between electrocatalyst performance and key material descriptors. Leveraging its unparalleled speed and accuracy, ML has facilitated the discovery of novel candidates and the improvement of known products through its pattern recognition capabilities. This review aims to provide a tailored breakdown of ML applications in a format that is readily accessible to materials scientists. Hence, we comprehensively organize ML-driven research by commonly studied material types for different electrochemical reactions to illustrate how ML adeptly navigates the complex landscape of descriptors for these scenarios. We further highlight ML's critical role in the future discovery and development of electrocatalysts for hydrogen energy transformation. Potential challenges and gaps to fill within this focused domain are also discussed. As a practical guide, we hope this work will bridge the gap between communities and encourage novel paradigms in electrocatalysis research, aiming for more effective and sustainable energy solutions.

Evolution and Antigenic Differentiation of Avian Influenza A(H7N9) Virus, China.

We characterized the evolution and molecular characteristics of avian influenza A(H7N9) viruses isolated in China during 2021-2023. We systematically analyzed the 10-year evolution of the hemagglutinin gene to determine the evolutionary branch. Our results showed recent antigenic drift, providing crucial clues for updating the H7N9 vaccine and disease prevention and control.

Upregulation of hsa-miR-141-3p promotes uterine cervical carcinoma progression via targeting dual-specificity protein phosphatase 1.

We aimed to explore the aberrant expression status of hsa-miR-141-3p and dual-specificity protein phosphatase 1 (DUSP1) and their relative mechanisms in uterine cervical carcinoma (UCC).Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was conducted to detect the expression of hsa-miR-141-3p. Immunohistochemical (IHC) staining was performed to examine the expression of DUSP1 in UCC. Gene chips and RNA-seq datasets were also obtained to assess the expression level. Integrated standardized mean difference (SMD) was calculated to evaluate the expression status of hsa-miR-141-3p in UCC tissues comprehensively. DUSP1-overexpression and hsa-miR-141-3p-inhibition HeLa cells were established, and CCK-8, transwell, wound healing, cell cycle, and apoptosis assays were implemented. The targets of hsa-miR-141-3p were obtained with online tools, and the combination of hsa-miR-141-3p and DUSP1 was validated via dual-luciferase reporter assay. Single-cell RNA-seq data were analyzed to explore hsa-miR-141-3p and DUSP1 in different cells. An integrated SMD of 1.41 (95% CI[0.45, 2.38], p = 0.0041) with 558 samples revealed the overexpression of hsa-miR-141-3p in UCC tissues. And the pooled SMD of -1.06 (95% CI[-1.45, -0.66], p < 0.0001) with 1,268 samples indicated the downregulation of DUSP1. Inhibition of hsa-miR-141-3p could upregulate DUSP1 expression and suppress invasiveness and metastasis of HeLa cells. Overexpression of DUSP1 could hamper proliferation, invasion, and migration and boost apoptosis and distribution of G1 phase. The dual-luciferase reporter assay validated the combination of hsa-miR-141-3p and DUSP1. Moreover, the targets of hsa-miR-141-3p were mainly enriched in the MAPK signaling pathway and activated in fibroblasts and endothelial cells. The current study illustrated the upregulation of hsa-miR-141-3p and the downregulation of DUSP1 in UCC tissues. Hsa-miR-141-3p could promote UCC progression by targeting DUSP1.

Deep Learning Assisted Classification of T1ρ-MR Based Intervertebral Disc Degeneration Phases.

BACKGROUND: According to the T1ρ value of nucleus pulposus, our previous study has found that intervertebral disc degeneration (IDD) can be divided into three phases based on T1ρ-MR, which is helpful for the selection of biomaterial treatment timing. However, the routine MR sequences for patients with IDD are T1- and T2-MR, T1ρ-MR is not commonly used due to long scanning time and extra expenses, which limits the application of T1ρ-MR based IDD phases. PURPOSE: To build a deep learning model to achieve the classification of T1ρ-MR based IDD phases from routine T1-MR images. STUDY TYPE: Retrospective. POPULATION: Sixty (M/F: 35/25) patients with low back pain or lower limb radiculopathy are randomly divided into training (N = 50) and test (N = 10) sets. FIELD STRENGTH/SEQUENCES: 1.5 T MR scanner; T1-, T2-, and T1ρ-MR sequence (spin echo). ASSESSMENT: The T1ρ values of the nucleus pulposus in intervertebral discs (IVDs) were measured. IVDs were divided into three phases based on the mean T1ρ value: pre-degeneration phase (mean T1ρ value >110 msec), rapid degeneration phase (mean T1ρ value: 80-110 msec), and late degeneration phase (mean T1ρ value <80 msec). After measurement, the T1ρ values, phases, and levels of IVDs were input into the model as labels. STATISTICAL TESTS: Intraclass correlation coefficient, area under the receiver operating characteristic curve (AUC), F1-score, accuracy, precision, and recall (P < 0.05 was considered significant). RESULTS: In the test dataset, the model achieved a mean average precision of 0.996 for detecting IVD levels. The diagnostic accuracy of the T1ρ-MR based IDD phases was 0.840 and the AUC was 0.871, the average AUC of 5-folds cross validation was 0.843. DATA CONCLUSION: The proposed deep learning model achieved the classification of T1ρ-MR based IDD phases from routine T1-MR images, which may provide a method to facilitate the application of T1ρ-MR in IDD. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Leflunomide alleviates obesity via activation of the TAK1-AMPK pathway and induction of lipophagy.

Lipophagy is a subset of selective autophagy that specifically degrades lipid droplets and plays an important role in obesity. Leflunomide treatment in rheumatoid arthritis (RA) patients has been associated with weight loss and decreased blood glucose levels, which cannot be attributed to its known side effects. Our prior studies showed that A77 1726, the active metabolite of leflunomide, acts as an inhibitor of S6K1 to sensitize the insulin receptor and control hyperglycemia. Whether the anti-obesity effect of leflunomide is mediated by targeting S6K1 and its underlying mechanisms remain unclear. Here, we report that A77 1726 induced LC3 lipidation and increased the formation of autophagosomes and lipoautolysosomes in 3T3-L1 adipocytes by activating TGF-ß-activated kinase 1 (TAK1), AMP-activated kinase (AMPK), and Unc-51 like autophagy-activated kinase 1 (ULK1). A77 1726 reduced the content of lipid droplets in 3T3-L1 adipocytes, which was blocked by bafilomycin or by beclin-1 knockdown. Similar observations were made in murine adipocytes differentiated from S6K1-/- embryonic fibroblasts (MEFs). Leflunomide treatment restricted bodyweight gains in ob/ob mice and reduced the visceral fat deposit and the size of adipocytes. Leflunomide treatment induced autophagy in adipose and liver tissues and reduced hepatic lipid contents. Consistently, S6K1 knockout increased the levels of LC3 lipidation in the liver, muscle, and fat of S6K-/- mice. Leflunomide treatment and S6K1 deficiency both induced TAK1, AMPK, and ULK1 phosphorylation in these tissues. These observations collectively suggest that leflunomide controls obesity in part by activating AMPK and inducing lipophagy. Our study provides insights into the mechanisms of leflunomide-mediated anti-obesity activity.

Insect herbivory on woody broadleaf seedlings along a subtropical elevational gradient supports the resource concentration hypothesis.

PREMISE: Theories of plant-herbivore interactions hold that seedlings are more vulnerable to herbivory in warmer and more stable climates at lower elevations. Hypotheses of plant apparency, resource concentration, and resource availability have been proposed to explain variability in leaf herbivory. However, seasonal differences in the effects of these hypotheses on leaf herbivory on seedlings remain unclear. METHODS: We evaluated the three herbivory hypotheses by comparing the percentage and frequency of leaf herbivory in understory broadleaf seedlings in a subtropical forest in May (spring) and October (autumn) along an elevational gradient (290-1370 m a.s.l.). In total, we measured 2890 leaves across 696 seedlings belonging to 95 species and used beta regressions to test the effects of plant apparency (e.g., leaf area, seedling height), resource concentration (e.g., plant species diversity), and resource availability (e.g., canopy openness, soil available N and P) on leaf herbivory. RESULTS: Seedlings exhibited unimodal patterns of leaf herbivory along elevation, with drivers of leaf herbivory varying by the month. Variation in the frequency of leaf herbivory was best explained by the resource concentration hypothesis (e.g., plant species diversity) in both months, and herbivory was lower on seedlings in sites with higher plant diversity. Plant apparency hypothesis (e.g., leaf area, seedling height) was weakly supported only in spring, and the evidence for resource availability hypothesis (e.g., canopy openness, soil nutrients) was mixed. CONCLUSIONS: This study supports the resource concentration hypothesis and reveals the importance of seasonal difference on understanding leaf herbivory patterns and the drivers of plant diversity in subtropical forests.

In Situ Electrochemical Construction of CuN3@CuCl Hybrids for Controllable Energy Release and Self-Passivation Ability.

Advanced energetic materials (EMs) play a crucial role in the advancement of microenergetic systems as actuation parts, igniters, propulsion units, and power. The sustainable electrosynthesis of EMs has gained momentum and achieved substantial improvements in the past decade. This study presents the facile synthesis of a new type of high-performance CuN3@CuCl hybrids via a co-electrodeposition methodology utilizing porous Cu as the sacrificial template. The composition, morphology, and energetic characteristics of the CuN3@CuCl hybrids can be easily tuned by adjusting the deposition times. The resulting hybrids demonstrate remarkable energy output (1120 J·g-1) and good laser-induced initiating ability. As compared with porous CuN3, the uniform doping of inert CuCl enhances the electrostatic safety of the hybridized material without compromising its overall energetic characteristics. Notably, the special oxidizing behavior of CuCl gradually lowers the susceptibility of the hybrid material to laser and electrostatic stimulation. This has significant implications for the passivation or self-destruction of highly sensitive EMs. Overall, this study pioneers a new path for the development of MEMS-compatible EMs, facilitating further microenergetic applications.

Pt on Atomic-Layered WO3 Islands: Electronic Tuning of Platinum-Tungsten Heterostructures for Highly Efficient Low-Temperature VOC Combustion.

Adjusting the electronic state of noble metal catalysts on a nanoscale is crucial for optimizing the performance of nanocatalysts in many important environmental catalytic reactions, particularly in volatile organic compound (VOC) combustion. This study reports a novel strategy for optimizing Pt catalysts by modifying their electronic structure to enhance the electron density of Pt. The research illustrates the optimal 0.2Pt-0.3W/Fe2O3 heterostructure with atomic-thick WO3 layers as a bulking block to electronically modify supported Pt nanoparticles. Methods such as electron microscopy, X-ray photoelectron spectroscopy, and in situ Fourier transform infrared spectroscopy confirm Pt's electron-enriched state resulting from electron transfer from atomic-thick WO3. Testing for benzene oxidation revealed enhanced low-temperature activity with moderate tungsten incorporation. Kinetic and mechanistic analyses provide insights into how the enriched electron density benefits the activation of oxygen and the adsorption of benzene on Pt sites, thereby facilitating the oxidation reaction. This pioneering work on modifying the electronic structure of supported Pt nanocatalysts establishes an innovative catalyst design approach. The electronic structure-performance-dependent relationships presented in this study assist in the rational design of efficient VOC abatement catalysts, contributing to clean energy and environmental solutions.

LncRNA JPX targets SERCA2a to mitigate myocardial ischemia/reperfusion injury by binding to EZH2.

Long non-coding RNAs (lncRNAs) are pivotal regulators in heart disease, including myocardial ischemia/reperfusion (I/R) injury. LncRNA just proximal to XIST (JPX) is a molecular switch for X-chromosome inactivation. Enhancer of zeste homolog 2 (EZH2) is a core catalytic subunit of the polycomb repressive complex 2 (PRC2), which is involved in chromatin compaction and gene repression. This study aims to explore the mechanism of JPX regulating the expression of Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) by binding to EZH2 and preventing cardiomyocyte I/R damage in vivo and in vitro. First, we constructed mouse myocardial I/R and HL1 cell hypoxia/reoxygenation models, and found that JPX was low expressed in both models. JPX overexpression alleviated cardiomyocyte apoptosis in vivo and in vitro, reduced the I/R-induced infarct size in mouse hearts, lowered the serum cTnI concentration, and promoted mouse cardiac systolic function. The evidence implies that JPX can alleviate I/R-induced acute cardiac damage. Mechanistically, the FISH and RIP assays showed that JPX could bind to EZH2. The ChIP assay revealed EZH2 enrichment at the promoter region of SERCA2a. Both the EZH2 and H3K27me3 levels at the promoter region of SERCA2a were reduced in the JPX overexpression group compared to those in the Ad-EGFP group (P < 0.01). In summary, our results suggested that LncRNA JPX directly bound to EZH2 and reduced the EZH2-mediated H3K27me3 in the SERCA2a promoter region, protecting the heart from acute myocardial I/R injury. Therefore, JPX might be a potential therapeutic target for I/R injury.

The inverted internal limiting membrane flap technique is not recommended for the treatment of large macular holes smaller than 650 µm.

PURPOSE: To compare the anatomical and functional outcomes of the inverted flap technique versus conventional internal limited membrane (ILM) peeling in large idiopathic full-thickness macular holes (FTMHs) smaller than 650 µm. METHODS: Retrospective comparative study. Patients with large idiopathic MHs smaller than 650 µm who underwent either the inverted flap technique (IFT) or ILM peeling were investigated. The main outcomes included the MH closure rate, recovery rates of the external limiting membrane (ELM) and ellipsoid zone (EZ) and best-corrected visual acuity (BCVA) at 1, 3, and 6 months postoperatively. RESULTS: Sixty-nine eyes of 69 patients who underwent the IFT (n = 32, group A) or ILM peeling (n = 37, group B) were included. In both groups, a significant BCVA improvement was acquired throughout the follow-up period. The mean BCVA increased at each follow-up visit in both groups (P<.001). However, the IFT group showed poorer visual results than the ILM peeling group at all time points (P=0.039, 0.005, 0.006). The ELM recovery rate in the ILM peeling group (78.3%, 29/37 eyes) was higher than that in the IFT group (53.1%, 17/32 eyes) at six months after surgery (p = 0.079). CONCLUSION: The IFT resulted in poorer ELM and visual recovery than ILM peeling, suggesting that the IFT is not a suitable option for repairing large MHs < 650 µm.

Association between triglyceride glucose index-related indices with gallstone disease among US adults.

BACKGROUND: Triglyceride glucose (TyG) index combined with obesity-related indicators [triglyceride glucose-body mass index (TyG-BMI), triglyceride glucose-waist to height ratio (TyG-WHtR), triglyceride glucose-waist circumference (TyG-WC)], represents emerging methodologies for assessing insulin resistance. The objective of this investigation was to explore the correlation between TyG-related indices and gallstone disease. METHODS: The study included 3740 adults from the 2017-2020 period of the National Health and Nutrition Examination Survey. TyG-BMI, TyG-WC, and TyG-WHtR were integrated as both continuous and categorical variables within the multivariate logistic model, respectively to evaluate the connection between various TyG-related indices and gallstone disease. Additionally, restriction cubic splines and subgroup analysis were employed to deepen our understanding of this relationship. RESULTS: When analyzed as continuous variables, positive correlations were observed between TyG-BMI, TyG-WC, TyG-WHtR and gallstone disease. The OR(95%CI) were 1.063(1.045,1.082) for TyG-BMI (per 10-unit), 1.026(1.018,1.034) for TyG-WC (per 10-unit) and 1.483(1.314,1.676) for TyG-WHtR (per 1-unit), respectively. When categorized into quartiles, these three TyG-related indices still show statistically significant associations with gallstone disease. Descending in order, the diagnostic capability for gallstone disease is demonstrated as follows: TyG-WHtR (AUC = 0.667), TyG-BMI (AUC = 0.647), and TyG-WC (AUC = 0.640). CONCLUSION: There were significantly positive associations between TyG-related indices, including TyG-BMI, TyG-WC, and TyG-WHtR, and gallstone disease. Of these indices, TyG-WHtR demonstrated the most favorable performance in identifying the risk of gallstone disease.

Risk and Protective Factors for Parental Involvement and Early Indicators of School Achievement in Alaska.

OBJECTIVES: Parental involvement can affect child school readiness, which in turn influences subsequent child learning outcomes. While social support, stress, caregiver psychological distress, and drinking could affect parental involvement, it is unknown whether and how these factors influence downstream child learning outcomes through parental involvement and child school readiness. This study tests those associations. METHODS: Using de-identified data provided by the Alaska Longitudinal Child Abuse and Neglect Linkage project (N = 683), we use Structural Equation Modeling to assess direct and indirect effects of paths embedded in the proposed model. RESULTS: This study found statistically significant indirect effects: (1) path linking stress faced by caregivers to child reading proficiency through caregiver psychological distress, parental involvement, and child school readiness, (2) path linking stress faced by caregivers to child reading proficiency through caregiver drinking, parental involvement, and child school readiness, and (3) path linking social support for caregivers to child reading proficiency through caregiver psychological distress, parental involvement, and child school readiness. Post-estimation showed that the sum of the magnitude of total effects of stress and the magnitude of total effects of support is significantly larger than either alone. CONCLUSIONS FOR PRACTICE: Findings suggest that reducing caregiver stress and offering social support could not only benefit caregivers but learning outcomes of their children as well. For child learning outcomes, simultaneously reducing stress and offering social support for caregivers, rather than just one of them alone, is suggested. These results are important for children, particularly for those raised by caregivers experiencing psychological distress or drinking issues.

Genome-Wide Identification of the WRKY Gene Family and Functional Characterization of CpWRKY5 in Cucurbita pepo.

The WRKY gene family is crucial for regulating plant growth and development. However, the WRKY gene is rarely studied in naked kernel formation in hull-less Cucurbita pepo L. (HLCP), a natural mutant that lacks the seed coat. In this research, 76 WRKY genes were identified through bioinformatics-based methods in C. pepo, and their phylogenetics, conserved motifs, synteny, collinearity, and temporal expression during seed coat development were analyzed. The results showed that 76 CpWRKYs were identified and categorized into three main groups (I-III), with Group II further divided into five subgroups (IIa-IIe). Moreover, 31 segmental duplication events were identified in 49 CpWRKY genes. A synteny analysis revealed that C. pepo shared more collinear regions with cucumber than with melon. Furthermore, quantitative RT-PCR (qRT-PCR) results indicated the differential expression of CpWRKYs across different varieties, with notable variations in seed coat development between HLCP and CP being attributed to differences in CpWRKY5 expression. To investigate this further, CpWRKY5-overexpression tobacco plants were generated, resulting in increased lignin content and an upregulation of related genes, as confirmed by qRT-PCR. This study offers valuable insights for future functional investigations of CpWRKY genes and presents novel information for understanding the regulation mechanism of lignin synthesis.

B-Type Natriuretic Peptide Inhibits the Expression and Function of SERCA2a in Heart Failure.

B-type natriuretic peptide (BNP) possesses protective cardiovascular properties; however, there has not been sufficient serious consideration of the side effects of BNP. As for sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a), it was once considered a new target for the treatment of heart failure (HF). Nevertheless, clinical trials of SERCA2a gene therapy in HF have finally become unsuccessful. Research has found that elevated BNP levels and decreased SERCA2a expression are two important HF characteristics, which are always negatively correlated. We hypothesize that BNP inhibits SERCA2a expression and, therefore, exerts negative effects on SERCA2a expression and function.The effects of BNP on endogenous SERCA2a expression and function were tested in mice with HF induced by transverse aortic constriction and neonatal rat cardiomyocytes (NRCM). Furthermore, to verify the effects of BNP on exogenous SERCA2a gene transduction efficacy, BNP was added to the myocardium and cardiomyocytes infected with an adenovirus overexpressing SERCA2a.In vivo, BNP levels were increased, SERCA2a expression was reduced in both the BNP intervention and HF groups, and BNP reduced the overexpressed exogenous SERCA2a protein in the myocardium. Our in vitro data showed that BNP dose-dependently inhibited the total and exogenous SERCA2a expression in NRCM by activating the cGMP-dependent protein kinase G. BNP also inhibited the effects of SERCA2a overexpression on Ca2+ transience in NRCM.The expression and function of endogenous and exogenous SERCA2a are inhibited by BNP. The opposite relationship between BNP and SERCA2a should be given serious attention in the treatment of HF via BNP or SERCA2a gene therapy.

China special issue on gastrointestinal tumors-Radiological features of pathological complete response in mismatch repair deficient colorectal cancer after neoadjuvant PD-1 blockade: A post hoc analysis of the PICC phase II trial.

Neoadjuvant programmed cell death protein 1 (PD-1) blockade exhibits promising efficacy in patients with mismatch repair deficient (dMMR) colorectal cancer (CRC). However, discrepancies between radiological and histological findings have been reported in the PICC phase II trial (NCT03926338). Therefore, we strived to discern radiological features associated with pathological complete response (pCR) based on computed tomography (CT) images. Data were obtained from the PICC trial that included 36 tumors from 34 locally advanced dMMR CRC patients, who received neoadjuvant PD-1 blockade for 3 months. Among the 36 tumors, 28 (77.8%) tumors achieved pCR. There were no statistically significant differences in tumor longitudinal diameter, the percentage change in tumor longitudinal diameter from baseline, primary tumor sidedness, clinical stage, extramural venous invasion status, intratumoral calcification, peritumoral fat infiltration, intestinal fistula and tumor necrosis between the pCR and non-pCR tumors. Otherwise, tumors with pCR had smaller posttreatment tumor maximum thickness (median: 10 mm vs 13 mm, P = .004) and higher percentage decrease in tumor maximum thickness from baseline (52.9% vs 21.6%, P = .005) compared to non-pCR tumors. Additionally, a higher proportion of the absence of vascular sign (P = .003, odds ratio [OR] = 25.870 [95% CI, 1.357-493.110]), nodular sign (P < .001, OR = 189.000 [95% CI, 10.464-3413.803]) and extramural enhancement sign (P = .003, OR = 21.667 [2.848-164.830]) was observed in tumors with pCR. In conclusion, these CT-defined radiological features may have the potential to serve as valuable tools for clinicians in identifying patients who have achieved pCR after neoadjuvant PD-1 blockade, particularly in individuals who are willing to adopt a watch-and-wait strategy.

CT-based deep learning model for the prediction of DNA mismatch repair deficient colorectal cancer: a diagnostic study.

BACKGROUND: Stratification of DNA mismatch repair (MMR) status in patients with colorectal cancer (CRC) enables individual clinical treatment decision making. The present study aimed to develop and validate a deep learning (DL) model based on the pre-treatment CT images for predicting MMR status in CRC. METHODS: 1812 eligible participants (training cohort: n = 1124; internal validation cohort: n = 482; external validation cohort: n = 206) with CRC were enrolled from two institutions. All pretherapeutic CT images from three dimensions were trained by the ResNet101, then integrated by Gaussian process regression (GPR) to develop a full-automatic DL model for MMR status prediction. The predictive performance of the DL model was evaluated using the area under the receiver operating characteristic curve (AUC) and then tested in the internal and external validation cohorts. Additionally, the participants from institution 1 were sub-grouped by various clinical factors for subgroup analysis, then the predictive performance of the DL model for identifying MMR status between participants in different groups were compared. RESULTS: The full-automatic DL model was established in the training cohort to stratify the MMR status, which presented promising discriminative ability with the AUCs of 0.986 (95% CI 0.971-1.000) in the internal validation cohort and 0.915 (95% CI 0.870-0.960) in the external validation cohort. In addition, the subgroup analysis based on the thickness of CT images, clinical T and N stages, gender, the longest diameter, and the location of tumors revealed that the DL model showed similar satisfying prediction performance. CONCLUSIONS: The DL model may potentially serve as a noninvasive tool to facilitate the pre-treatment individualized prediction of MMR status in patients with CRC, which could promote the personalized clinical-making decision.

Molecular interactions in short-chain perfluoroalkyl carboxylic acids and aqueous solutions.

The presence of short-chain per- and polyfluoroalkyl substances in water poses a major health and environmental challenge. Here, we have performed high-energy small- and wide-angle X-ray scattering measurements on CF3[CF2]nCOOH (where n = 1, 2, 3 represents the chain length) and their aqueous solutions at 10% mole concentrations to characterize their molecular interactions at the atomic and nanometer length scales. The experimental wide-angle structure factors have been modelled using Empirical Potential Structural Refinement. The oxygen-oxygen partial X-ray pair distribution functions show that the coordination number between the hydroxyl oxygen on the acid and surrounding oxygen water molecules increases significantly with acid chain length, rising from 3.2 for n = 1 to 4.1 for n = 3. The small-angle scattering is dominated by a sharp, high-intensity peak at Q1 ∼ 0.2 Å-1 and a smaller peak at Q2 = 1.2 Å-1 for n = 3, both of which decrease with decreasing chain length. The Q2 peak is attributed to groups of adjacent non-bonded acid molecules, and Q1 has contributions from both correlations between acid molecules and water-water interactions. In all cases, the models show nanoscale aggregation occurs in the form of denser channels of winding hydrogen-bonded chains, approximately 20 water molecules in length, surrounding clusters of acid molecules. This article is part of the theme issue 'Exploring the length scales, timescales and chemistry of challenging materials (Part 2)'.

Screening of antigenic epitopes related to the adhesion of the avian Escherichia coli Type 1 Fimbrial Agglutinin Domain.

BACKGROUND: Avian Escherichia coli (E.coli) type 1 fimbriae adhere to avian tracheal epithelial cells through the FimH protein. However, the adhesion-related antigen is still unknown. The purpose of this study was to analyze the antigenicity of the type 1 fimbrial FimH protein of wild-type avian E. coli, screen antigen epitopes, and prepare monoclonal antibodies (mAbs) that can block the adhesion of avian E. coli. RESULTS: In this study, the nucleic acid homologies of MG2 (O11), TS12 (O18), and YR5 (O78) with K12 were 97.7%, 99.6%, and 97.7%, respectively, and the amino acid sequence similarity reached 98.7%, 99.3%, and 98.0%, respectively. The epitopes and hydrophilicities of the FimH proteins of these three strains were similar. The more obvious lectin domain epitopes were located at FimH protein positions 111-124 and 154-162. The mAbs 7C2 and 7D8 against these two epitopes were prepared. An adhesion inhibition test showed that 7C2 and 7D8 blocked bacterial adhesion to avian tracheal epithelial cells. The mAb 7C2 against the 111-124 epitope inhibited O78 strain adhesion by 93%, and the mAb 7D8 against the 154-162 epitope inhibited O78 strain adhesion by 49%, indicating that these two epitopes are closely related to the adhesion of type 1 fimbriae. However, only the 111-124 epitope-recognizing mAb 7C2 inhibited bacterial agglutination of erythrocytes, indicating that host cell receptor binding and erythrocyte agglutination are not mediated by the same spatial locations within the FimH protein. CONCLUSIONS: The results demonstrate that the mAbs 7C2 and 7D8 against FimH protein positions 111-124 and 154-162 could inhibit the adhesion of E.coli to the chicken trachea.

The evaluation of coronary microvascular obstruction in patients with STEMI by cardiac magnetic resonance T2-STIR image and layer-specific analysis of 2-dimensional speckle tracking echocardiography combined with low-dose dobutamine stress echocardiography.

This study was designed to assess coronary microvascular obstruction (MVO) in patients with acute ST-segment elevation myocardial infarction (STEMI) by cardiac magnetic resonance T2-weighted short tau inversion recovery (T2-STIR) image and layer-specific analysis of 2-dimensional speckle tracking echocardiography combined with low-dose dobutamine stress echocardiography (LDDSE-LS2D-STE). 32 patients were enrolled to perform cardiac magnetic resonance and echocardiography 5-7 days after primary percutaneous coronary intervention. Infarcted myocardium was categorized into MVO+ group and MVO- group by late gadolinium enhancement as gold standard. At T2-weighted image, the area of hyper-intense region and hypo-intense core inside were marked as A1, A2 and A2/A1 > 0 represented MVO. Strain parameters were composed of longitudinal strain (LS), circumferential strain and radial strain at rest and dobutamine stress. There were 94 MVO+ segments, 136 MVO- segments according to gold standard. 96 segments had hypo-intense core at T2-STIR image. The sensitivity and specificity of T2-STIR in detecting MVO were 91.49 and 92.65%. Endocardial LS was superior to other parameters, and stress endocardial LS was higher than that of resting endocardial LS (sensitivity: 77.11% vs 72.29%, specificity: 93.28% vs 83.19%, AUC: 0.87 vs 0.82, P < 0.05). The combination of T2-STIR and stress endocardial LS in parallel test could improve sensitivity significantly (98.05% vs 91.49%). T2-STIR has higher diagnostic value in detecting MVO with some limitations. However, LDDSE-LS2D-STE with cost-effective and handling may be a good alternative to T2-STIR. It provides additional and reliable diagnostic tools to identify MVO in STEMI patients after reperfusion.