Exercise accelerates recruitment of CD8+ T cell to promotes anti-tumor immunity in lung cancer via epinephrine.

BACKGROUND AND PURPOSE: In recent years, there has been extensive research on the role of exercise as an adjunctive therapy for cancer. However, the potential mechanisms underlying the anti-tumor therapy of exercise in lung cancer remain to be fully elucidated. As such, our study aims to confirm whether exercise-induced elevation of epinephrine can accelerate CD8+ T cell recruitment through modulation of chemokines and thus ultimately inhibit tumor progression. METHOD: C57BL/6 mice were subcutaneously inoculated with Lewis lung cancer cells (LLCs) to establish a subcutaneous tumor model. The tumor mice were randomly divided into different groups to performed a moderate-intensity exercise program on a treadmill for 5 consecutive days a week, 45 min a day. The blood samples and tumor tissues were collected after exercise for IHC, RT-qPCR, ELISA and Western blot. In addition, another group of mice received daily epinephrine treatment for two weeks (0.05 mg/mL, 200 µL i.p.) (EPI, n = 8) to replicate the effects of exercise on tumors in vivo. Lewis lung cancer cells were treated with different concentrations of epinephrine (0, 5, 10, 20 µM) to detect the effect of epinephrine on chemokine levels via ELISA and RT-qPCR. RESULTS: This study reveals that both pre- and post-cancer exercise effectively impede the tumor progression. Exercise led to an increase in EPI levels and the infiltration of CD8+ T cell into the lung tumor. Exercise-induced elevation of EPI is involved in the regulation of Ccl5 and Cxcl10 levels further leading to enhanced CD8+ T cell infiltration and ultimately inhibiting tumor progression. CONCLUSION: Exercise training enhance the anti-tumor immunity of lung cancer individuals. These findings will provide valuable insights for the future application of exercise therapy in clinical practice.

[Characteristics of Microorganisms and Antibiotic Resistance Genes of the Riparian Soil in the Lanzhou Section of the Yellow River].

Riparian soil is a critical area of watersheds. The characteristics of biological contaminants in riparian soil affect the pollution control of the watershed water environment. Thus, the microbial community structure, antibiotic resistance genes (ARGs), and mobile genetic elements (MGEs) in the riparian soil of the Lanzhou section of the Yellow River were investigated by analyzing the characteristics of soil samples collected from farmland, mountains, and industrial land. The results showed that the Proteobacteria, Bacteroidetes, and Actinobacteria were the dominant phyla in the riparian soil of Lanzhou section of the Yellow River. The microbial structure in the riparian soil was significantly correlated with the land use type (P < 0.05). The α diversity index of bacterial communities in land types was in the order of farmland > mountain > industry. Sulfonamide-typed ARGs were the most dominant genes in the soil of the Lanzhou section of the Yellow River Basin, among which the sul1 gene had the highest abundance, 20-36 000 times that of other detected ARGs. Moreover, the total absolute abundance of ARGs in industrial soil was the highest. Principal coordinate analysis (PCoA) displayed that the ARGs characteristics had a significant correlation with land types (P < 0.05), and intl1 and tnpA-04 drove the diffuseness of sulfonamide and tetracycline ARGs, respectively. Redundancy analysis (RDA) demonstrated that the content of inorganic salt ions and total phosphorus in the soil of the riparian zone of the Yellow River Lanzhou section were the main environmental factors, modifying the distribution of the microbial structure. Halobacterota and Acidobacteriota were the main microflora that drove the structural change in ARGs.

Predicting ischemic stroke patients' prognosis changes using machine learning in a nationwide stroke registry.

Accurately predicting the prognosis of ischemic stroke patients after discharge is crucial for physicians to plan for long-term health care. Although previous studies have demonstrated that machine learning (ML) shows reasonably accurate stroke outcome predictions with limited datasets, to identify specific clinical features associated with prognosis changes after stroke that could aid physicians and patients in devising improved recovery care plans have been challenging. This study aimed to overcome these gaps by utilizing a large national stroke registry database to assess various prediction models that estimate how patients' prognosis changes over time with associated clinical factors. To properly evaluate the best predictive approaches currently available and avoid prejudice, this study employed three different prognosis prediction models including a statistical logistic regression model, commonly used clinical-based scores, and a latest high-performance ML-based XGBoost model. The study revealed that the XGBoost model outperformed other two traditional models, achieving an AUROC of 0.929 in predicting the prognosis changes of stroke patients followed for 3 months. In addition, the XGBoost model maintained remarkably high precision even when using only selected 20 most relevant clinical features compared to full clinical datasets used in the study. These selected features closely correlated with significant changes in clinical outcomes for stroke patients and showed to be effective for predicting prognosis changes after discharge, allowing physicians to make optimal decisions regarding their patients' recovery.

Using U-Net convolutional neural network to model pixel-based electrostatic potential distributions in GaN power MIS-HEMTs.

This study demonstrates a novel use of the U-Net convolutional neural network (CNN) for modeling pixel-based electrostatic potential distributions in GaN metal-insulator-semiconductor high-electron mobility transistors (MIS-HEMTs) with various gate and source field plate designs and drain voltages. The pixel-based images of the potential distribution are successfully modeled from the developed U-Net CNN with an error of less than 1% error relative to a TCAD simulated reference of a 500-V electrostatic potential distribution in the AlGaN/GaN interface. Furthermore, the modeling time of potential distributions by U-Net takes about 80 ms. Therefore, the U-Net CNN is a promising approach to efficiently model the pixel-based distributions characteristics in GaN power devices.

Associations of urinary fetuin-A with histopathology and kidney events in biopsy-proven kidney disease.

Background: Fetuin-A is implicated in the pathogenesis of vascular calcification in chronic kidney disease (CKD); however, the relationship between fetuin-A, histopathologic lesions and long-term kidney outcomes in patients with various types of kidney disease remains unclear. Methods: We measured urinary fetuin-A levels in 335 individuals undergoing clinically indicated native kidney biopsy. The expressions of fetuin-A mRNA and protein in the kidney were assessed using RNA sequencing and immunohistochemistry. The association of urinary fetuin-A with histopathologic lesions and major adverse kidney events (MAKE), defined as a decline in estimated glomerular filtration rate (eGFR) of at least 40%, kidney failure or death, was analyzed. Results: Urinary fetuin-A levels showed a positive correlation with albuminuria (rs = 0.67, P < .001) and a negative correlation with eGFR (rs = -0.46, P < .001). After multivariate adjustment, higher urinary fetuin-A levels were associated with glomerular inflammation, mesangial expansion, interstitial fibrosis and tubular atrophy, and arteriolar sclerosis. Using a 1 transcript per million gene expression cutoff, we found kidney fetuin-A mRNA levels below the threshold in both individuals with normal kidney function and those with CKD. Additionally, immunohistochemistry revealed reduced fetuin-A staining in tubular cells of CKD patients compared with normal controls. During a median 21-month follow-up, 115 patients experienced MAKE, and Cox regression analysis confirmed a significant association between elevated urinary fetuin-A and MAKE. This association remained significant after adjusting for potential confounding factors. Conclusion: Urinary fetuin-A is associated with chronic histological damage and adverse clinical outcomes across a spectrum of biopsy-proven kidney diseases.

Palladium-Catalyzed Asymmetric Decarboxylation of 5-Vinyloxazolidine-2,4-Diones Triggering the Dearomatization of Electron-Deficient Indoles for the Synthesis of Chiral Highly Functionalized Pyrroloindolines.

A catalyst system consisting of a chiral phosphoramidite ligand and Pd2(dba)3·CHCl3 causes the decarboxylation of 5-vinyloxazolidine-2,4-diones to generate amide-containing aza-π-allylpalladium 1,3-dipole intermediates, which are capable of triggering the dearomatization of 3-nitroindoles for diastereo- and enantioselective [3+2] cycloaddition, leading to the formation of a series of highly functionalized pyrroloindolines containing three contiguous stereogenic centers with excellent results (up to 99% yield, 88:12 dr, and 96% ee).

In vivo SPECT imaging of Tc-99 m radiolabeled exosomes from human umbilical-cord derived mesenchymal stem cells in small animals.

Extracellular vesicles derived from human umbilical cord-derived mesenchymal stem cells (UCMSC-EVs) have been postulated to have therapeutic potential for various diseases. However, the biodistribution and pharmacokinetics of these vesicles are still unclear. For a better understanding of the in vivo properties of UCMSC-EVs, in the present study, these vesicles were first radiolabeled with Technetium-99 m (99mTc-UCMSC-EVs) and evaluated using in vivo single photon emission computed tomography (SPECT) imaging and biodistribution experiments. SPECT images demonstrated that the liver and spleen tissues mainly took up the 99mTc-UCMSC-EVs. The biodistribution study observed slight uptake in the thyroid and stomach, indicating that 99mTc-UCMSC-EVs was stable at 24 h in vivo. The pharmacokinetic analyses of the blood half-life demonstrated the quick distribution phase (0.85 ±â€¯0.28 min) and elimination phase (25.22 ±â€¯20.76 min) in mice. This study provides a convenient and efficient method for 99mTc-UCMSC-EVs preparation without disturbing their properties. In conclusion, the biodistribution, quick elimination, and suitable stability in vivo of 99mTc-UCMSC-EVs were quantified by the noninvasive imaging and pharmacokinetic analyses, which provides useful information for indication selection, dosage protocol design, and toxicity assessment in future applications.

A New Dy(III) Complex: Fluorescence Performances, Loading with Resveratrol-Hydrogels Against Skin Aging and Molecular Docking.

In the present research, novel lanthanide coordination compounds [DyL(PhCOO)(CH3OH)](ClO4)2·(CH3OH)2 (1) were characterized by the compression of 2,6-diformyl-4-methyl-phenol (dmp) and 1,3-diamino-2-propanol using benzoate as the secondary ligand, where L indicates the deprotonated macrocyclic ligand. Through the high structural rigidity driven by the coordination of the macrocyclic ligand formed by condensation in methanol solution and sodium benzoate with Dy(ClO4)3·6H2O, compound 1 exhibits outstanding cyan-emitting fluorescence performance and potential applications as a fluorescent material. Additionally, hyaluronic acid (HA)/ carboxymethyl chitosan (CMCS) hydrogels were prepared with loaded resveratrol metal-organic complexes according to the synthetic chemical approach. In biological study, we evaluated the effect of hydrogels on oxidative stress on human dermal fibroblasts. Examined by molecular docking simulation, the results showed that the binding interactions were from the phenol group, the carboxyl group and also the "-N=" group, indicating Dy metal complex has excellent biological capability.

Can small bowel obstruction during pregnancy be treated with conservative management? A review.

BACKGROUND: Small bowel obstruction can occur during pregnancy, which, if missed, can lead to dire consequences for both the mother and foetus. Management of this condition usually requires surgical intervention. However, only a small number of patients are treated conservatively. OBJECTIVE: The objective was to review the literature to determine the feasibility of conservative management for small bowel obstruction. METHODS: A systematic search of the PubMed and Embase databases was performed using the keywords [small bowel obstruction AND pregnancy]. All original articles were then reviewed and included in this review if deemed suitable. CONCLUSION: Conservative management of small bowel obstruction in pregnant women is feasible if the patient is clinically stable and after ruling out bowel ischaemia and closed-loop obstruction.

Development and evaluation of a deep learning-based model for simultaneous detection and localization of rib and clavicle fractures in trauma patients' chest radiographs.

Purpose: To develop a rib and clavicle fracture detection model for chest radiographs in trauma patients using a deep learning (DL) algorithm. Materials and methods: We retrospectively collected 56 145 chest X-rays (CXRs) from trauma patients in a trauma center between August 2008 and December 2016. A rib/clavicle fracture detection DL algorithm was trained using this data set with 991 (1.8%) images labeled by experts with fracture site locations. The algorithm was tested on independently collected 300 CXRs in 2017. An external test set was also collected from hospitalized trauma patients in a regional hospital for evaluation. The receiver operating characteristic curve with area under the curve (AUC), accuracy, sensitivity, specificity, precision, and negative predictive value of the model on each test set was evaluated. The prediction probability on the images was visualized as heatmaps. Results: The trained DL model achieved an AUC of 0.912 (95% CI 87.8 to 94.7) on the independent test set. The accuracy, sensitivity, and specificity on the given cut-off value are 83.7, 86.8, and 80.4, respectively. On the external test set, the model had a sensitivity of 88.0 and an accuracy of 72.5. While the model exhibited a slight decrease in accuracy on the external test set, it maintained its sensitivity in detecting fractures. Conclusion: The algorithm detects rib and clavicle fractures concomitantly in the CXR of trauma patients with high accuracy in locating lesions through heatmap visualization.

Research progress on insect visual electrophysiological techniques.

Insect visual electrophysiological techniques are important to study the electrical characteristics of photoreceptor cells and visual neurons in insects, including electroretinography (ERG) and microelectrode intracellular recording (MIR). ERG records the changes of voltage or electric current in the retina of insects in response to different light stimuli, which occurs outside the cell. MIR records the changes in individual photoreceptor cells or visual neurons of an insect exposed to different lights, which occurs inside the cell. Insect visual electrophysiological techniques can explore the mechanism of electrophysiological response of insects' vision to light and reveal their sensitive light spectra and photoreceptor types. This review introduced the basic structure and the principle of ERG and MIR, and summarized their applications in insect researches in the past 20 years, which would provide references for elucidating the mechanism of light perception in insects and the use of insect phototropism to control pests.

Liver regeneration of living donor after liver donation for transplantation: Disparity in the left and right remnant liver.

Donor safety is crucial for living donor liver transplantation (LDLT), and sufficient liver regeneration significantly affects outcomes of living donors. This study aimed to investigate clinical factors associated with liver regeneration in living donors. The study retrospectively reviewed 380 living donors who underwent liver donation at Chang Gung Memorial Hospital in Linkou. The clinical characteristics and medical parameters of donors were analyzed and compared according to liver donation graft type. There were 355 donors (93.4%) with right hemi-liver donations and 25 donors (6.6%) with left hemi-liver donations. Left hemi-liver donors had a higher body mass index (BMI) and a larger ratio of remnant liver volume (RLV) to total liver volume (TLV). However, the 2 groups showed no significant difference in the liver regeneration ratio. The type of remnant liver (P < .001), RLV/body weight (P = .027), RLV/TLV (P < .001), serum albumin on postoperative day 7 and total bilirubin levels on postoperative day 30 were the most significant factors affecting liver regeneration in living donors. In conclusion, adequate liver regeneration is essential for donor outcome after liver donation. The remnant liver could eventually regenerate to an adequate volume similar to the initial TLV before liver donation. However, the remnant left hemi-liver had a faster growth rate than the remnant right hemi-liver in donors.

Synthesis of Benzofuro[3,2-b]indol-3-one Derivatives via Dearomative (3 + 2) Cycloaddition of 2-Nitrobenzofurans and para-Quinamines.

An efficient dearomative (3 + 2) cycloaddition of para-quinamines and 2-nitrobenzofurans has been developed. This reaction proceeds smoothly under mild conditions and affords a series of benzofuro[3,2-b]indol-3-one derivatives in good to excellent yields (up to 98%) with perfect diastereoselectivities (all cases > 20:1 dr). The scale-up synthesis and versatile derivatizations demonstrate the potential synthetic application of the protocol. A plausible reaction mechanism is also proposed to account for the observed reaction process. This work represents the first instance of the N-triggered dearomative (3 + 2) cycloaddition of 2-nitrobenzofurans.

Epidermal Growth Factor-Like Repeats and Discoidin I-Like Domains 3 Deficiency Attenuates Dilated Cardiomyopathy by Inhibiting Ubiquitin Specific Peptidase 10 Dependent Smad4 Deubiquitination.

BACKGROUND: Dilated cardiomyopathy (DCM) is the leading cause of heart failure with a poor prognosis. Recent studies suggest that endothelial to mesenchymal transition (EndMT) may be involved in the pathogenesis and cardiac remodeling during DCM development. EDIL3 (epidermal growth factor-like repeats and discoidin I-like domains 3) is an extracellular matrix glycoprotein that has been reported to promote EndMT in various diseases. However, the roles of EDIL3 in DCM still remain unclear. METHODS AND RESULTS: A mouse model of DCM and human umbilical vein endothelial cells were used to explore the roles and mechanisms of EDIL3 in DCM. The results indicated that EndMT and EDIL3 were activated in DCM mice. EDIL3 deficiency attenuated cardiac dysfunction and remodeling in DCM mice. EDIL3 knockdown alleviated EndMT by inhibiting USP10 (ubiquitin specific peptidase 10) dependent Smad4 deubiquitination in vivo and in vitro. Recombinant human EDIL3 promoted EndMT via reinforcing deubiquitination of Smad4 in human umbilical vein endothelial cells treated with IL-1ß (interleukin 1ß) and TGF-ß (transforming growth factor beta). Inhibiting USP10 abolished EndMT exacerbated by EDIL3. In addition, recombinant EDIL3 also aggravates doxorubicin-induced EndMT by promoting Smad4 deubiquitination in HUVECs. CONCLUSIONS: Taken together, these results indicate that EDIL3 deficiency attenuated EndMT by inhibiting USP10 dependent Smad4 deubiquitination in DCM mice.

Bacteria-mediated resistance of neutrophil extracellular traps to enzymatic degradation drives the formation of dental calculi.

Dental calculi can cause gingival bleeding and periodontitis, yet the mechanism underlying the formation of such mineral build-ups, and in particular the role of the local microenvironment, are unclear. Here we show that the formation of dental calculi involves bacteria in local mature biofilms converting the DNA in neutrophil extracellular traps (NETs) from being degradable by the enzyme DNase I to being degradation resistant, promoting the nucleation and growth of apatite. DNase I inhibited NET-induced mineralization in vitro and ex vivo, yet plasma DNases were ineffective at inhibiting ectopic mineralization in the oral cavity in rodents. The topical application of the DNA-intercalating agent chloroquine in rodents fed with a dental calculogenic diet reverted NET DNA to its degradable form, inhibiting the formation of calculi. Our findings may motivate therapeutic strategies for the reduction of the prevalence of the deposition of bacteria-driven calculi in the oral cavity.

Comparison of continuous 24-hour and 14-day ECG monitoring for the detection of cardiac arrhythmias in patients with ischemic stroke or syncope.

BACKGROUND: Previous studies show that using 12-lead electrocardiogram (ECG) or 24-h ECG monitor for the detection of cardiac arrhythmia events in patients with stroke or syncope is ineffective. HYPOTHESIS: The 14-day continuous ECG patch has higher detection rates of arrhythmias compared with conventional 24-h ECG monitoring in patients with ischemic stroke or syncope. METHODS: This cross-sectional study of patients with newly diagnosed ischemic stroke or syncope received a 24-h ECG monitoring and 14-day continuous cardiac monitoring patch and the arrhythmia events were measured. RESULTS: This study enrolled 83 patients with ischemic stroke or syncope. The detection rate of composite cardiac arrhythmias was significantly higher for the 14-day ECG patch than 24-h Holter monitor (69.9% vs. 21.7%, p = .006). In patients with ischemic stroke, the detection rates of cardiac arrhythmias were 63.4% for supraventricular tachycardia (SVT), 7% for ventricular tachycardia (VT), 5.6% for atrial fibrillation (AF), 4.2% for atrioventricular block (AVB), and 1.4% for pause by 14-day ECG patch, respectively. The significant difference in arrhythmic detection rates were found for SVT (45.8%), AF (6%), pause (1.2%), AVB (2.4%), and VT (9.6%) by 14-day ECG patch but not by 24-h Holter monitor in patients with ischemic stroke or syncope. CONCLUSIONS: A 14-day ECG patch can be used on patients with ischemic stroke or syncope for the early detection of AF or other cardiac arrhythmia events. The patch can be helpful for physicians in planning medical or mechanical interventions of patients with ischemic stroke and occult AF.

Application of a multiplex molecular pneumonia panel and real-world impact on antimicrobial stewardship among patients with hospital-acquired and ventilator-associated pneumonia in intensive care units.

BACKGROUND: The optimal timing for applying the BioFire FilmArray Pneumonia Panel (FAPP) in intensive care unit (ICU) patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) remains undefined, and there are limited data on its impact on antimicrobial stewardship. METHODS: This retrospective study was conducted at a referral hospital in Taiwan from November 2019 to October 2022. Adult ICU patients with HAP/VAP who underwent FAPP testing were enrolled. Patient data, FAPP results, conventional microbiological testing results, and the real-world impact of FAPP results on antimicrobial therapy adjustments were assessed. Logistic regression was used to determine the predictive factors for bacterial detection by FAPP. RESULTS: Among 592 respiratory specimens, including 564 (95.3%) endotracheal aspirate specimens, 19 (3.2%) expectorated sputum specimens and 9 (1.5%) bronchoalveolar lavage specimens, from 467 patients with HAP/VAP, FAPP testing yielded 368 (62.2%) positive results. Independent predictors for positive bacterial detection by FAPP included prolonged hospital stay (odds ratio [OR], 3.14), recent admissions (OR, 1.59), elevated C-reactive protein levels (OR, 1.85), Acute Physiology and Chronic Health Evaluation II scores (OR, 1.58), and septic shock (OR, 1.79). Approximately 50% of antimicrobial therapy for infections caused by Gram-negative bacteria and 58.4% for Gram-positive bacteria were adjusted or confirmed after obtaining FAPP results. CONCLUSIONS: This study identified several factors predicting bacterial detection by FAPP in critically ill patients with HAP/VAP. More than 50% real-world clinical practices were adjusted or confirmed based on the FAPP results. Clinical algorithms for the use of FAPP and antimicrobial stewardship guidelines may further enhance its benefits.

Plantar pressure gradient and pressure gradient angle are affected by inner pressure of air insole.

Clinically, air insoles may be applied to shoes to decrease plantar pressure gradient (PPG) and increase plantar gradient angle (PGA) to reduce foot ulcers. PPG and PGA may cause skin breakdown. The effects of different inner pressures of inflatable air insoles on dynamic PPG and PGA distributions are largely unknown in non-diabetics and people with diabetes. This study aimed to explore the impact of varying inner air insole pressures on PPG and PGA to establish early mitigation strategies for people at risk of foot ulcers. A repeated measures study design, including three air insoles (80 mmHg, 160 mmHg, and 240 mmHg) and two walking durations (10 and 20 min) for a total of six walking protocols, was tested on 13 healthy participants (height, 165.8 ± 8.4 cm; age, 27.0 ± 7.3 years; and weight, 56.0 ± 7.9 kg, BMI: 20.3 ± 1.7 kg/m^2) over three consecutive weeks. PPG, a measurement of the spatial variation in plantar pressure around the peak plantar pressure (PPP) and PGA, a variation in the gradient direction values at the three plantar regions, big toe (T1), first metatarsal head (M1), and second metatarsal head (M2), were calculated. This study indicated that PPG was lower at 80 mmHg air insoles after 20 min of walking in the M1 region (p = 0.010). The PGA in the M2 increased at an air insole of 80 mmHg compared to 240 mmHg (p = 0.015). Compared to 20 min, the 10 min walking duration at 240 mmHg of air insole had the lowest PPG in the M1 (p = 0.015) and M2 (p = 0.034) regions. The 80 mmHg air insole significantly lowered the PPG compared to a 160 mmHg and 240 mmHg air insole. Moreover, the 80 mmHg air insole significantly decreased PPP and increased PGA compared to the 160 mmHg and 240 mmHg air insole. A shorter walking period (10 min) significantly lowered PPG. The findings of this study suggest that people with a higher risk of foot ulcers should wear softer air insoles to have a lower PPG, as well as an increased PGA.