Optimizing echo state networks for continuous gesture recognition in mobile devices: A comparative study.

Continuous gesture recognition can be used to enhance human-computer interaction. This can be accomplished by capturing human movement with the use of the Inertial Measurement Units in smartphones and using machine learning algorithms to predict the intended gestures. Echo State Networks (ESNs) consist of a fixed internal reservoir that is able to generate rich and diverse nonlinear dynamics in response to input signals that capture temporal dependencies within the signal. This makes ESNs well-suited for time series prediction tasks, such as continuous gesture recognition. However, their application has not been rigorously explored, with regard to gesture recognition. In this study, we sought to enhance the efficacy of ESN models in continuous gesture recognition by exploring diverse model structures, fine-tuning hyperparameters, and experimenting with various training approaches. We used three different training schemes that used the Leave-one-out Cross-validation (LOOCV) protocol to investigate the performance in real-world scenarios with different levels of data availability: Leaving out data from one user to use for testing (F1-score: 0.89), leaving out a fraction of data from all users to use in testing (F1-score: 0.96), and training and testing using LOOCV on a single user (F1-score: 0.99). The obtained results outperformed the Long Short-Term Memory (LSTM) performance from past research (F1-score: 0.87) while maintaining a low training time of approximately 13 seconds compared to 63 seconds for the LSTM model. Additionally, we further explored the performance of the ESN models through behaviour space analysis using memory capacity, Kernel Rank, and Generalization Rank. Our results demonstrate that ESNs can be optimized to achieve high performance on gesture recognition in mobile devices on multiple levels of data availability. These findings highlight the practical ability of ESNs to enhance human-computer interaction.

Phase 1/2 multicenter trial of acalabrutinib in Chinese patients with relapsed/refractory mantle cell lymphoma.

Acalabrutinib studies have limited Asian participation. This phase 1/2 study (NCT03932331) assessed acalabrutinib in Chinese patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). Primary endpoint was blinded independent central review (BICR)-assessed overall response rate (ORR). Overall, 34 patients were enrolled. Most patients were men (88%); median age was 63 years and 59% had ≥3 prior treatments. Median treatment duration was 14 months (range, 1-24). Any-grade adverse events (AEs) and grade ≥3 AEs occurred in 85.3% and 44.1% of patients, respectively. AEs causing treatment discontinuation were aplastic anemia, thrombocytopenia, and gastrointestinal infection (n = 1 each). Fatal AEs occurred in 2 patients (aplastic anemia and multiple organ dysfunction syndrome [n = 1 each]). BICR-assessed ORR was 82.4% (95% confidence interval [CI]: 65.5, 93.2); 12 (35.3%) patients achieved complete response. Estimated 12-month OS was 84.5% (95% CI: 66.6, 93.3). Acalabrutinib yielded tolerable safety and high response rates in Chinese patients with R/R MCL.

Multidimensional Frailty Instruments Can Predict Acute Exacerbations Within One Year in Patients with Stable Chronic Obstructive Pulmonary Disease: A Retrospective Longitudinal Study.

Background: Chronic obstructive pulmonary disease (COPD) is closely associated with frailty, and prevention of acute exacerbations is important for disease management. Moreover, COPD patients with frailty experience a higher risk of acute exacerbations. However, the frailty instruments that can better predict acute exacerbations remain unclear. Purpose: (1) To explore the factors influencing frailty and acute exacerbations in stable COPD patients, and (2) quantify the ability of multidimensional frailty instruments to predict acute exacerbations within 1 year. Patients and methods: In this retrospective longitudinal study, stable COPD patients were recruited from the outpatient department of Sichuan Provincial People's Hospital from July 2022 to June 2023. COPD patients reviewed their frailty one year ago and their acute exacerbations within one year using face-to-face interviews with a self-developed frailty questionnaire. Frailty status was assessed using the Frailty Index (FI), frailty questionnaire (FRAIL), and Clinical Frailty Scale (CFS). One-way logistic regression was used to explore the factors influencing frailty and acute exacerbations. Multivariate logistic regression was used to establish a prediction model for acute exacerbations, and the accuracy of the three frailty instruments was compared by measuring the area under the receiver operating characteristic curve (AUC). Results: A total of 120 individuals were included. Frailty incidence estimates using FI, FRAIL, and CFS were 23.3%, 11.7%, and 15.8%, respectively. The three frailty instruments showed consistency in COPD assessments (P<0.05). After adjusting for covariates, frailty reflected by the FI and CFS score remained an independent risk factor for acute exacerbations. The CFS score was the best predictor of acute exacerbations (AUC, 0.764 (0.663-0.866); sensitivity, 57.9%; specificity, 80.0%). Moreover, the combination of CFS plus FRAIL scores was a better predictor of acute exacerbations (AUC, 0.792 (0.693-0.891); sensitivity, 86.3%; specificity, 60.0%). Conclusion: Multidimensional frailty assessments could improve the identification of COPD patients at high risk of acute exacerbations and facilitate targeted interventions to reduce acute exacerbations in these patients.

The rising roles of exosomes in the tumor microenvironment reprogramming and cancer immunotherapy.

Exosomes are indispensable for intercellular communications. Tumor microenvironment (TME) is the living environment of tumor cells, which is composed of various components, including immune cells. Based on TME, immunotherapy has been recently developed for eradicating cancer cells by reactivating antitumor effect of immune cells. The communications between tumor cells and TME are crucial for tumor development, metastasis, and drug resistance. Exosomes play an important role in mediating these communications and regulating the reprogramming of TME, which affects the sensitivity of immunotherapy. Therefore, it is imperative to investigate the role of exosomes in TME reprogramming and the impact of exosomes on immunotherapy. Here, we review the communication role of exosomes in regulating TME remodeling and the efficacy of immunotherapy, as well as summarize the underlying mechanisms. Furthermore, we also introduce the potential application of the artificially modified exosomes as the delivery systems of antitumor drugs. Further efforts in this field will provide new insights on the roles of exosomes in intercellular communications of TME and cancer progression, thus helping us to uncover effective strategies for cancer treatment.

The AGAMOUS-LIKE 16-GENERAL REGULATORY FACTOR 1 module regulates axillary bud outgrowth via catabolism of abscisic acid in cucumber.

Lateral branches are important components of shoot architecture and directly affect crop yield and production cost. Although sporadic studies have implicated abscisic acid (ABA) biosynthesis in axillary bud outgrowth, the function of ABA catabolism and its upstream regulators in shoot branching remain elusive. Here, we showed that the MADS-box transcription factor AGAMOUS-LIKE 16 (CsAGL16) is a positive regulator of axillary bud outgrowth in cucumber (Cucumis sativus). Functional disruption of CsAGL16 led to reduced bud outgrowth, whereas overexpression of CsAGL16 resulted in enhanced branching. CsAGL16 directly binds to the promoter of the ABA 8'-hydroxylase gene CsCYP707A4 and promotes its expression. Loss of CsCYP707A4 function inhibited axillary bud outgrowth and increased ABA levels. Elevated expression of CsCYP707A4 or treatment with an ABA biosynthesis inhibitor largely rescued the Csagl16 mutant phenotype. Moreover, cucumber General Regulatory Factor 1 (CsGRF1) interacts with CsAGL16 and antagonizes CsAGL16-mediated CsCYP707A4 activation. Disruption of CsGRF1 resulted in elongated branches and decreased ABA levels in the axillary buds. The Csagl16 Csgrf1 double mutant exhibited a branching phenotype resembling that of the Csagl16 single mutant. Therefore, our data suggest that the CsAGL16-CsGRF1 module regulates axillary bud outgrowth via CsCYP707A4-mediated ABA catabolism in cucumber. Our findings provide a strategy to manipulate ABA levels in axillary buds during crop breeding to produce desirable branching phenotypes.

Dynamic multicolor emissions of multimodal phosphors by Mn2+ trace doping in self-activated CaGa4O7.

The manipulation of excitation modes and resultant emission colors in luminescent materials holds pivotal importance for encrypting information in anti-counterfeiting applications. Despite considerable achievements in multimodal and multicolor luminescent materials, existing options generally suffer from static monocolor emission under fixed external stimulation, rendering them vulnerability to replication. Achieving dynamic multimodal luminescence within a single material presents a promising yet challenging solution. Here, we report the development of a phosphor exhibiting dynamic multicolor photoluminescence (PL) and photo-thermo-mechanically responsive multimodal emissions through the incorporation of trace Mn2+ ions into a self-activated CaGa4O7 host. The resulting phosphor offers adjustable emission-color changing rates, controllable via re-excitation intervals and photoexcitation powers. Additionally, it demonstrates temperature-induced color reversal and anti-thermal-quenched emission, alongside reproducible elastic mechanoluminescence (ML) characterized by high mechanical durability. Theoretical calculations elucidate electron transfer pathways dominated by intrinsic interstitial defects and vacancies for dynamic multicolor emission. Mn2+ dopants serve a dual role in stabilizing nearby defects and introducing additional defect levels, enabling flexible multi-responsive luminescence. This developed phosphor facilitates evolutionary color/pattern displays in both temporal and spatial dimensions using readily available tools, offering significant promise for dynamic anticounterfeiting displays and multimode sensing applications.

Carbon nanotube-encapsulated Co/Co3Fe7 heterojunctions as a highly-efficient bifunctional electrocatalyst for rechargeable zinc-air batteries.

In oxygen electrocatalysis, how to rationally design low-cost catalysts with reasonable structure and long-term stability is a crucial issue. Here, an in-situ growth strategy is used to construct a shaped structure encapsulating a uniformly-dispersed Co/Co3Fe7 heterojunction in nitrogen-doped carbon nanotubes (Co/Co3Fe7@NCNTs). Hollow CoFe layered-double-hydroxide prisms act as sacrifices for in-situ growth of Co/Co3Fe7 nanoparticles, which also catalyze the growth of bamboo-like NCNTs. Tubular structure not only accelerates the charge transfer through the interactions between Co and Co3Fe7, but also limits the aggregation of the particles, thereby promoting the 4e- oxygen reduction/evolution reactions (ORR/OER) kinetics and stabilizing the bifunctional activity. Co/Co3Fe7@NCNTs-800 (pyrolyzed at 800 °C) shows exceptional ORR activity (half-wave potential of 0.89 V) and methanol tolerance. Meanwhile, Co/Co3Fe7@NCNTs-800 shows a small OER overpotential of 280 mV, which increases by only 9 mV after 1000 cyclic voltammetry (CV) cycles. The outstanding bifunctionality (potential gap of 0.62 V) is ascribed to the electronic structure modulation at the Co/Co3Fe7 heterointerface. Notably, it also has a high performance as an air-cathode for rechargeable zinc-air battery, showing high power density (165 mW cm-2) and specific capacity (770.5 m Ah kg-1). This work provides a new reference for promoting the development of alloy catalysts with heterogeneous interfaces.

Boosted Second Harmonic Generation and Cascaded Sum Frequency Generation from a Surface Crystallized Glass Ceramic Microcavity.

The development of novel materials and structures for efficient second-order nonlinear micro/nano devices remains a significant challenge. In this study, the remarkable enhancement of second-harmonic generation (SHG) and cascaded sum frequency generation in whispering gallery mode microspheres made of surface-crystallized glass with a 6-µm Ba2TiSi2O8 crystal layer are demonstrated. Attributed to the core-shell design, the Ba2TiSi2O8 located on the surface can be efficiently coupled with whispering gallery modes, resulting in a highly efficient micron-scale cavity-enhanced second-order optical nonlinearity. Greatly enhanced SHG of the microcavity is observed, which is up to 80 times stronger than that of a non-resonant sample. Furthermore, owing to the wavelength non-selectivity of random quasi-phase matching, ultra-wideband SHG with a strong response ranging from 860 to 1600 nm and high-contrast polarization characteristics is demonstrated. The glass-ceramic-based microsphere cavity also boosts the cascading optical nonlinearity, manifested by a two-magnitude enhancement of cascaded sum frequency generation. This work delineates an efficient strategy for boosting nonlinear optical response in glass ceramics, which will open up new opportunities for applications in photonics and optical communications.

Two-Dimensional Os2Se3 Nanosheet: A Ferroelectric Metal with Room-Temperature Ferromagnetism.

Two-dimensional (2D) ferroelectric metals (FEMs) possess intriguing characteristics, such as unconventional superconductivity and the nonlinear anomalous Hall effect. However, their occurrence is exceedingly rare due to mutual repulsion between ferroelectricity and metallicity. In addition, further incorporating other features like ferromagnetism into FEMs to enhance their functionalities poses a significantly greater challenge. Here, via first-principles calculations, we demonstrate a case of an FEM that features a coexistence of room-temperature ferromagnetism, ferroelectricity, and metallicity in a thermodynamically stable 2D Os2Se3. It presents a vertical electric polarization of 3.00 pC/m that exceeds those of most FEMs and a moderate polarization switching barrier of 0.22 eV per formula unit. Moreover, 2D Os2Se3 exhibits robust ferromagnetism (Curie temperature TC ≈ 527 K) and a sizable magnetic anisotropy energy (-30.87 meV per formula unit). Furthermore, highly magnetization-dependent electrical conductivity is revealed, indicative of strong magnetoelectric coupling. Berry curvature calculation suggests that the FEM might exhibit nontrivial band topology.

Optimization of Preparation Conditions for Quercetin Nanoliposomes Using Response Surface Methodology and Evaluation of Their Stability.

Quercetin is a flavonol compound with excellent biological activities. However, quercetin exhibits poor stability and solubility in water, which limits its application. In this study, quercetin nanoliposomes (QUE-NL-1) were prepared using an ultrasonic thin-film dispersion method, and the preparation conditions were optimized using response surface methodology. The optimal conditions for preparing QUE-NL-1 were as follows: an evaporation temperature of 35 °C, a drug concentration of 0.20 mg/mL, and a lipid bile ratio of 4:1. The encapsulation rate of QUE-NL-1 is (63.73 ± 2.09)%, the average particle size is 134.11 nm, and the average absolute value of the zeta potential is 37.50 and PDI = 0.24. By analyzing the storage temperature, storage time, and leakage rate of QUE-NL-1 in simulated gastrointestinal fluid, it was found that quercetin exhibits good stability after embedding and can achieve sustained release in intestinal juice. In addition, the cytotoxicity of QUE-NL-1 was not significant, and the survival rate of Caco-2 cells was >90% when the concentration range of QUE-NL-1 was 0.1-0.4 mg/mL. This study provides an efficient method for preparing QUE-NL-1 with small particle sizes, good stability, and high safety, which is of great significance for expanding the application range of quercetin.

A Dual-mode platform for the rapid detection of Escherichia coli O157:H7 based on CRISPR/Cas12a and RPA.

Escherichia coli O157:H7 (E. coli O157:H7) is a foodborne pathogenic microorganism that is commonly found in the environment and poses a significant threat to human health, public safety, and economic stability worldwide. Thus, early detection is essential for E. coli O157:H7 control. In recent years, a series of E. coli O157:H7 detection methods have been developed, but the sensitivity and portability of the methods still need improvement. Therefore, in this study, a rapid and efficient testing platform based on the CRISPR/Cas12a cleavage reaction was constructed. Through the integration of recombinant polymerase amplification and lateral flow chromatography, we established a dual-interpretation-mode detection platform based on CRISPR/Cas12a-derived fluorescence and lateral flow chromatography for the detection of E. coli O157:H7. For the fluorescence detection method, the limits of detection (LODs) of genomic DNA and E. coli O157:H7 were 1.8 fg/µL and 2.4 CFU/mL, respectively, within 40 min. Conversely, for the lateral flow detection method, LODs of 1.8 fg/µL and 2.4 × 102 CFU/mL were achieved for genomic DNA and E. coli O157:H7, respectively, within 45 min. This detection strategy offered higher sensitivity and lower equipment requirements than industry standards. In conclusion, the established platform showed excellent specificity and strong universality. Modifying the target gene and its primers can broaden the platform's applicability to detect various other foodborne pathogens.

Discovery of two predictable (3,18)-connected topologies based on Wells-Dawson type cages for the design of porous metal phosphonocarboxylate frameworks.

Highly connected molecular building blocks (MBBs) have been demonstrated to play a crucial role in reticular chemistry, particularly in predicting the topologies of metal-organic frameworks. Metal phosphonate clusters exhibit considerable advantages in constructing high-connectivity MBBs, owing to the multiple coordination modes offered by phosphonic ligands. Herein, four metal (M = CoII, MnII) phosphonocarboxylate frameworks (CoPCF-1,2 and MnPCF-1,2) were successfully prepared under solvothermal conditions by utilizing the phosphonocarboxylic ligand, 4'-phosphonobiphenyl-3,5-dicarboxylic acid (H4pbpdc), and their structural characterization was performed using single-crystal X-ray diffraction (SCXRD). The structures feature a duodenary nuclear M12(µ3-OH)2(CO2)12(PO3)6(DMF)6/(CH3COO)4.5 cluster, bearing resemblance to the well-known Wells-Dawson ion from polyoxometallate chemistry. It is the first time a Wells-Dawson type cage has served as an 18-connected molecular building block, forming two kinds of porous metal phosphonocarboxylate frameworks with novel (3,18)-connected gez and gea topologies. Their permanent porosities were confirmed through N2 adsorption studies. Notably, the MBB Co12 cluster-based CoPCF-1 shows a loss and recovery process of µ3-OH through single-crystal-to-single-crystal (SCSC) transformation. The magnetic properties of the four compounds exhibit antiferromagnetic behavior.

Comparison of bicarbonate Ringer's solution with lactated Ringer's solution among postoperative outcomes in patients with laparoscopic right hemihepatectomy: a single-centre randomised controlled trial.

The study was aimed to investigate the positive impact of bicarbonate Ringer's solution on postoperative outcomes in patients who underwent laparoscopic right hemihepatectomy. Patients in the two groups were infused with lactated Ringer's solution (LRS, n = 38) and the bicarbonate Ringer's solution (BRS, n = 38) at a rate of 5 ml·kg-1·h-1. The stroke volume was monitored and 200 ml of hydroxyethyl starch with 130/0.4 sodium chloride injection (Hes) of a bolus was given in the first 5-10 min. The main outcome was to test lactic acid (LAC) concentration before and after surgery. The concentrations of LAC in the LRS group were higher than in the BRS group at 2 h after operation began, at the end of the operation and 2 h after the operation. Overall, the parameters including pH, base excess (BE), HCO3-, aspartate transaminase (AST) and alanine transaminase (ALT) were improved. The values of bilirubin in the LRS group were higher and albumin were lower than in the BRS group at post-operation 1st and 2nd day (P<0.05). The time of prothrombin time (PT) and activated partial thromboplastin time (APTT) in the LRS group were longer than that in the BRS group at post-operation 1st and 2nd day (P<0.05). Likewise, the concentrations of Mg2+, Na+ and K+ also varied significantly. The length of hospital was reduced, and the incidence of premature ventricular contractions (P = 0.042) and total complications (P = 0.016) were lower in group BRS. TRIAL REGISTRATION: The study was registered at clinicalTrials.gov with the number ChiCTR2000038077 on 09/09/2020.

[Hemicellulose modification and cell wall genetic improvement in plants].

Hemicellulose, as a primary component of plant cell walls, constitutes approximately one third of cell wall dry matter and ranks as the second abundant renewable biomass resource in the nature after cellulose. Hemicellulose is tightly cross-linked with cellulose, lignin and other components in the plant cell wall, leading to lignocellulose recalcitrance. However, precise genetic modifications of plant cell walls can significantly improve the saccharification efficiency of lignocellulose while ensuring normal plant growth and development. We comprehensively review the research progress in the structural distribution of hemicellulose in plant cell walls, the cross-linking between hemicellulose and other components of the cell wall, and the impact of hemicellulose modification on the saccharification efficiency of the cell wall, proving a reference for the genetic improvement of energy crops.

Perioperative outcomes and long-term survival of cryosurgery on unresectable pancreatic cancer: a systematic review and meta-analysis.

BACKGROUND: Pancreatic cancer (PC) continues to rank as one of the deadliest forms of cancer, with the majority of patients being diagnosed with unresectable disease. The implementation of cryoablation-based comprehensive treatment is expected to lead to a reduction in tumor size and potentially achieve complete resection. However, the availability of systematic and evidence-based treatment guidelines for cryoablation in pancreatic cancer is currently limited. MATERIALS AND METHODS: A computerized search was conducted in the Medline, Embase, Cochrane Library databases, and Clinicaltrials to retrieve studies published from August 1987 to June 2023. The perioperative outcomes and long-term survival of patients with locally advanced pancreatic cancer (LAPC) or metastatic pancreatic cancer (mPC) who underwent cryosurgery were systematically collected. Heterogeneity was assessed using the Cochran's Q test, and a funnel plot was implemented to evaluate publication bias. Data were pooled and analyzed using Stata 14.0 software. The Newcastle-Ottawa Quality Assessment Form tool was employed for quality evaluation. RESULTS: 9 studies including 368 patients were identified. The pooled overall incidence rate was 4% (95%CI: 0-14%; I²=54.06%) for acute pancreatitis, 0% (95%CI: 0-0%; I²=0.0%) for delayed gastric emptying, 0% (95%CI: 0-1%; I²=0.0%) for postoperative pancreatic fistula (POPF) or bile leakage, 2% (95%CI:0-5%; I²=0.0%) for bleeding, and 4% (95%CI: 0-12%; I²=70.46%) for fever. Our subgroup analysis revealed that the percutaneous treatment group had a lower incidence of complications compared to laparotomy, but had higher incidences of POPF, bleeding, and pancreatitis than the intraoperative group. Median overall survival (OS) varied from 5 to 16.2 months. The median survival rates at 6, 12, 24, and 36 months for patients who underwent cryosurgery were as follows: 94.9%, 64.8% (range: 4.8%-63.1%), 22.80%, and 9.5%, respectively. CONCLUSION: With the advancements in cryoablation and anti-tumor therapy, cryoablation emerges as a promising treatment modality for patients with unresectable pancreatic cancer. According to existing literature, the combination of cryoablation with radioactive particle implantation or immunotherapy has demonstrated considerable efficacy and safety. However, while the majority of included data is derived from retrospective studies, it is imperative to conduct larger sample sizes or prospective trials for further validation.

Unveiling diverse coordination-defined electronic structures of reconstructed anatase TiO2(001)-(1 × 4) surface.

Transition metal oxides (TMOs) exhibit fascinating physicochemical properties, which originate from the diverse coordination structures between the transition metal and oxygen atoms. Accurate determination of such structure-property relationships of TMOs requires to correlate structural and electronic properties by capturing the global parameters with high resolution in energy, real, and momentum spaces, but it is still challenging. Herein, we report the determination of characteristic electronic structures from diverse coordination environments on the prototypical anatase-TiO2(001) with (1 × 4) reconstruction, using high-resolution angle-resolved photoemission spectroscopy and scanning tunneling microscopy/atomic force microscopy, in combination with density functional theory calculation. We unveil that the shifted positions of O 2s and 2p levels and the gap-state Ti 3p levels can sensitively characterize the O and Ti coordination environments in the (1 × 4) reconstructed surface, which show distinguishable features from those in bulk. Our findings provide a paradigm to interrogate the intricate reconstruction-relevant properties in many other TMO surfaces.

Development and Validation of a Deep-Learning Network for Detecting Congenital Heart Disease from Multi-View Multi-Modal Transthoracic Echocardiograms.

Early detection and treatment of congenital heart disease (CHD) can significantly improve the prognosis of children. However, inexperienced sonographers often face difficulties in recognizing CHD through transthoracic echocardiogram (TTE) images. In this study, 2-dimensional (2D) and Doppler TTEs of children collected from 2 clinical groups from Beijing Children's Hospital between 2018 and 2022 were analyzed, including views of apical 4 chamber, subxiphoid long-axis view of 2 atria, parasternal long-axis view of the left ventricle, parasternal short-axis view of aorta, and suprasternal long-axis view. A deep learning (DL) framework was developed to identify cardiac views, integrate information from various views and modalities, visualize the high-risk region, and predict the probability of the subject being normal or having an atrial septal defect (ASD) or a ventricular septaldefect (VSD). A total of 1,932 children (1,255 healthy controls, 292 ASDs, and 385 VSDs) were collected from 2 clinical groups. For view classification, the DL model reached a mean [SD] accuracy of 0.989 [0.001]. For CHD screening, the model using both 2D and Doppler TTEs with 5 views achieved a mean [SD] area under the receiver operating characteristic curve (AUC) of 0.996 [0.000] and an accuracy of 0.994 [0.002] for within-center evaluation while reaching a mean [SD] AUC of 0.990 [0.003] and an accuracy of 0.993 [0.001] for cross-center test set. For the classification of healthy, ASD, and VSD, the model reached the mean [SD] accuracy of 0.991 [0.002] and 0.986 [0.001] for within- and cross-center evaluation, respectively. The DL models aggregating TTEs with more modalities and scanning views attained superior performance to approximate that of experienced sonographers. The incorporation of multiple views and modalities of TTEs in the model enables accurate identification of children with CHD in a noninvasive manner, suggesting the potential to enhance CHD detection performance and simplify the screening process.

Superoxide dismutase alterations in COVID-19: implications for disease severity and mortality prediction in the context of omicron variant infection.

Background: In the few reports to date, the changes in superoxide dismutase (SOD), a key factor in cellular protection against superoxide, in COVID-19 have been very inconsistent and contradictory. There is also a lack of data on COVID-19 induced by Omicron variant. Further investigation is warranted to figure out SOD alterations in COVID-19, particularly within the context of ongoing Omicron variant infection, which may provide clues to its role within COVID-19 pathogenesis and open up new avenues for COVID-19 treatment. Methods: SOD activity in 109 COVID-19 patients (including 46 severe cases and 63 mild to moderate cases) and 30 matched healthy controls were quantified. Demographic data, blood cell counts, biochemical indicators, coagulation indicators, and inflammatory markers were also recorded. Results: SOD, an important key node, experienced a significant decrease in COVID-19, with the severe patients exhibiting lower activity compared to the mild to moderate patients and control healthy. Notably, severe patients who deceased had the lowest SOD activity. Correlation analysis revealed significant correlations between SOD and inflammatory markers, organ injury markers, coagulation dysfunction indicators, nutritional markers, and lymphocytes counts. The ROC curve also showed good performance for the differentiation of severe cases and the prediction of death. Conclusion: SOD activity was significantly decreased in COVID-19 infected with Omicron variant and significantly correlated with systemic changes, and could be used as a biomarker to assess disease severity and predict mortality in COVID-19 clinical pathway management. Additionally, this finding will contribute to exploring new potential direction for the treatment of severe COVID-19 patients.

How do sphingosine-1-phosphate affect immune cells to resolve inflammation?

Inflammation is an important immune response of the body. It is a physiological process of self-repair and defense against pathogens taken up by biological tissues when stimulated by damage factors such as trauma and infection. Inflammation is the main cause of high morbidity and mortality in most diseases and is the physiological basis of the disease. Targeted therapeutic strategies can achieve efficient toxicity clearance at the inflammatory site, reduce complications, and reduce mortality. Sphingosine-1-phosphate (S1P), a lipid signaling molecule, is involved in immune cell transport by binding to S1P receptors (S1PRs). It plays a key role in innate and adaptive immune responses and is closely related to inflammation. In homeostasis, lymphocytes follow an S1P concentration gradient from the tissues into circulation. One widely accepted mechanism is that during the inflammatory immune response, the S1P gradient is altered, and lymphocytes are blocked from entering the circulation and are, therefore, unable to reach the inflammatory site. However, the full mechanism of its involvement in inflammation is not fully understood. This review focuses on bacterial and viral infections, autoimmune diseases, and immunological aspects of the Sphks/S1P/S1PRs signaling pathway, highlighting their role in promoting intradial-adaptive immune interactions. How S1P signaling is regulated in inflammation and how S1P shapes immune responses through immune cells are explained in detail. We teased apart the immune cell composition of S1P signaling and the critical role of S1P pathway modulators in the host inflammatory immune system. By understanding the role of S1P in the pathogenesis of inflammatory diseases, we linked the genomic studies of S1P-targeted drugs in inflammatory diseases to provide a basis for targeted drug development.

Riboflavin protects against pancreatic cancer metastasis by targeting TGF-ß receptor 1.

The inhibition of transforming growth factor-ß1 (TGF-ß1) signaling by targeting TGF-ß receptor 1 (TßR1) has been considered as an ideal approach for the prevention of pancreatic cancer metastasis. Utilizing a pharmacophore model for TßR1 inhibitors, candidate compounds with the potential TßR1 binding ability were screened from the U.S. Food and Drug Administration (FDA) database, and riboflavin (RF) with a highest fit value was chosen to investigate its binding ability to TßR1 and effect on TGF-ß1 signaling in pancreatic cancer cells. Molecular docking and cellular thermal shift assay (CETSA) proved that RF at pharmacological concentrations could directly bind to TßR1. Further studies showed that pharmacological concentrations of RF in vitro could block TGF-ß1 signaling, suppress the migration and invasion, and prevent epithelial-mesenchymal transition (EMT) process of pancreatic cancer cells in the absence or presence of TGF-ß1 stimulation, indicating that RF presented anti-metastatic effect in pancreatic cancer cells. Knockdown of TßR1 could significantly attenuate the effects of RF on the migration and EMT process in pancreatic cancer cells, further confirming that the anti-metastatic effect of RF was achieved by blocking TGF-ß1 signaling after binding to TßR1. Moreover, in a mouse model of pancreatic cancer metastasis, it was certified that RF administration could block lung and liver metastases, TGF-ß1 signaling and EMT process of pancreatic cancer in vivo. In summary, our findings showed that RF could block TGF-ß1 signaling by directly binding to TßR1, thereby suppressing the metastasis of pancreatic cancer cells by inhibiting EMT process both in vitro and in vivo.