Extracellular vesicles in endometriosis: role and potential.

Endometriosis is a chronic inflammatory gynecological disease, which profoundly jeopardizes women's quality of life and places a significant medical burden on society. The pathogenesis of endometriosis remains unclear, posing major clinical challenges in diagnosis and treatment. There is an urgent demand for the development of innovative non-invasive diagnostic techniques and the identification of therapeutic targets. Extracellular vesicles, recognized for transporting a diverse array of signaling molecules, have garnered extensive attention as a novel mode of intercellular communication. A burgeoning body of research indicates that extracellular vesicles play a pivotal role in the pathogenesis of endometriosis, which may provide possibility and prospect for both diagnosis and treatment. In light of this context, this article focuses on the involvement of extracellular vesicles in the pathogenesis of endometriosis, which deliver information among endometrial stromal cells, macrophages, mesenchymal stem cells, and other cells, and explores their potential applications in the diagnosis and treatment, conducing to the emergence of new strategies for clinical diagnosis and treatment.

An Artificial Intelligence-Driven Approach for Automatic Evaluation of Right-to-Left Shunt Grades in Saline-Contrasted Transthoracic Echocardiography.

BACKGROUND: Intracardiac or pulmonary right-to-left shunt (RLS) is a common cardiac anomaly associated with an increased risk of neurological disorders, specifically cryptogenic stroke. Saline-contrasted transthoracic echocardiography (scTTE) is often used for RLS diagnosis. However, the identification of saline microbubbles in the left heart can be challenging for novice residents, potentially leading to a delay in diagnosis and treatment. In this study, we proposed an artificial intelligence (AI)-based algorithm designed to automatically detect microbubbles in scTTE images and evaluate right-to-left shunt grades. This tool aims to support residency training and decrease the workload of cardiologists. METHODS: A dataset of 23,665 scTTE images obtained from 174 individuals was included in this study. This dataset was partitioned into a training set (n = 20,475) and an internal validation set (n = 3,190) on a patient-level basis. An additional cohort of 33 patients diagnosed with cryptogenic ischemic stroke was enrolled as an external validation set. The proposed algorithm for right-to-left shunt degree classification employed the EfficientNet-b4 model, and the model's performance was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity, and compared to the performance of residents. RESULTS: Our AI model demonstrated robust performance with an accuracy of 0.926, sensitivity of 0.827, and specificity of 0.951 on the internal testing dataset. In the external validation set, our AI model exhibited diagnostic accuracy, sensitivity, and specificity of 0.864, 0.818, and 0.909, respectively. In comparison, residents achieved values of 0.727, 0.636, and 0.818, respectively. CONCLUSION: Our AI model provides a swift, precise, and easily deployable methodology for grading the degree of right-to-left shunt in scTTE, carrying substantial implications for routine clinical practice. Residents can benefit from our artificial intelligence-based algorithm, enhancing both the accuracy and efficiency of RLS diagnosis.

Understanding the decomposition process of the Pt1Ag24(SPhCl2)18 nanocluster at the atomic level.

We report the decomposition of the Pt1Ag24(SPhCl2)18 nanocluster into a crown-like Pt1Ag4(SR)8 (SR = 2,4-SPhCl2 and 4-SPhBr) complex. UV-vis spectra and single crystal X-ray diffraction were used to track the structure-conversion process. Based on the total structure, the differences in ligand exchange rates at different sites and the effects on the stability were mapped out. This work can not only help us understand the ligand exchange behavior of the clusters, but also provide experimental support for the design of stable metal clusters.

Polystyrene nanoplastics with different functional groups and charges have different impacts on type 2 diabetes.

BACKGROUND: Increasing attention is being paid to the environmental and health impacts of nanoplastics (NPs) pollution. Exposure to nanoplastics (NPs) with different charges and functional groups may have different adverse effects after ingestion by organisms, yet the potential ramifications on mammalian blood glucose levels, and the risk of diabetes remain unexplored. RESULTS: Mice were exposed to PS-NPs/COOH/NH2 at a dose of 5 mg/kg/day for nine weeks, either alone or in a T2DM model. The findings demonstrated that exposure to PS-NPs modified by different functional groups caused a notable rise in fasting blood glucose (FBG) levels, glucose intolerance, and insulin resistance in a mouse model of T2DM. Exposure to PS-NPs-NH2 alone can also lead the above effects to a certain degree. PS-NPs exposure could induce glycogen accumulation and hepatocellular edema, as well as injury to the pancreas. Comparing the effect of different functional groups or charges on T2DM, the PS-NPs-NH2 group exhibited the most significant FBG elevation, glycogen accumulation, and insulin resistance. The phosphorylation of AKT and FoxO1 was found to be inhibited by PS-NPs exposure. Treatment with SC79, the selective AKT activator was shown to effectively rescue this process and attenuate T2DM like lesions. CONCLUSIONS: Exposure to PS-NPs with different functional groups (charges) induced T2DM-like lesions. Amino-modified PS-NPs cause more serious T2DM-like lesions than pristine PS-NPs or carboxyl functionalized PS-NPs. The underlying mechanisms involved the inhibition of P-AKT/P-FoxO1. This study highlights the potential risk of NPs pollution on T2DM, and provides a new perspective for evaluating the impact of plastics aging.

An Au5Ag12(SR)9(dppf)4 alloy nanocluster: structural determination and optical property and photothermal conversion investigation.

Photothermal conversion has garnered significant attention due to its potential for efficient energy conversion and application in targeted therapies. However, controlling photothermal properties at the atomic level remains a challenge in current materials synthesis. In this study, we report the synthesis and structural determination of a phosphine and mercaptan co-protected Au5Ag12(SR)9(dppf)4 (Au5Ag12) nanocluster with an extremely low quantum yield (∼0%). For comparative purposes, we synthesized three alloy nanoclusters of similar size. Notably, Au5Ag12 demonstrates a remarkably superior photothermal conversion performance, significantly outperforming the other clusters. We investigated this variance from both absorption and emission perspectives. This research not only opens new avenues for the application of clusters with extremely low quantum yields, but also provides experimental evidence for understanding the photothermal conversion properties of cluster materials at the atomic level.

Spacer Conformation Induced Multiple Hydrogen Bonds in 2D Perovskite toward Highly Efficient Optoelectronic Devices.

Two-dimensional (2D) Dion-Jacobson (DJ) perovskites typically outperform Ruddlesden-Popper (RP) analogs in terms of photodetection (PD). However, the mechanism behind this enhanced performance remains elusive. Theoretical calculations for elucidating interlayer spacer conformation-induced multiple hydrogen bonds in 2D perovskite are presented, along with the synthesis of DPAPbBr4 (DPB) single crystals (SCs) and their PD properties under X-ray/ultraviolet (UV) excitation. The high-quality DPB SC enhances PD with exceptional photoresponse attributes, including a high on/off ratio (4.89 × 104), high responsivity (2.44 A W⁻1), along with large dynamic linear range (154 dB) and low detection limit (7.1 nW cm⁻2), which are currently the best results among 2D perovskite SC detectors, respectively. Importantly, high-resolution images are obtained under UV illumination with weak light levels. The SC X-ray detector exhibits a high sensitivity of 663 µC Gyair⁻1 cm-2 at 10 V and a detection limit of 1.44 µGyair s⁻1. This study explores 2D DJ perovskites for efficient and innovative optoelectronic applications.

Gorilla optimization algorithm combining sine cosine and cauchy variations and its engineering applications.

To address the issues of lacking ability, loss of population diversity, and tendency to fall into the local extreme value in the later stage of optimization searching, resulting in slow convergence and lack of exploration ability of the artificial gorilla troops optimizer algorithm (AGTO), this paper proposes a gorilla search algorithm that integrates the positive cosine and Cauchy's variance (SCAGTO). Firstly, the population is initialized using the refractive reverse learning mechanism to increase species diversity. A positive cosine strategy and nonlinearly decreasing search and weight factors are introduced into the finder position update to coordinate the global and local optimization ability of the algorithm. The follower position is updated by introducing Cauchy variation to perturb the optimal solution, thereby improving the algorithm's ability to obtain the global optimal solution. The SCAGTO algorithm is evaluated using 30 classical test functions of Test Functions 2018 in terms of convergence speed, convergence accuracy, average absolute error, and other indexes, and two engineering design optimization problems, namely, the pressure vessel optimization design problem and the welded beam design problem, are introduced for verification. The experimental results demonstrate that the improved gorilla search algorithm significantly enhances convergence speed and optimization accuracy, and exhibits good robustness. The SCAGTO algorithm demonstrates certain solution advantages in optimizing the pressure vessel design problem and welded beam design problem, verifying the superior optimization ability and engineering practicality of the SCAGTO algorithm.

A multicenter clinical AI system study for detection and diagnosis of focal liver lesions.

Early and accurate diagnosis of focal liver lesions is crucial for effective treatment and prognosis. We developed and validated a fully automated diagnostic system named Liver Artificial Intelligence Diagnosis System (LiAIDS) based on a diverse sample of 12,610 patients from 18 hospitals, both retrospectively and prospectively. In this study, LiAIDS achieved an F1-score of 0.940 for benign and 0.692 for malignant lesions, outperforming junior radiologists (benign: 0.830-0.890, malignant: 0.230-0.360) and being on par with senior radiologists (benign: 0.920-0.950, malignant: 0.550-0.650). Furthermore, with the assistance of LiAIDS, the diagnostic accuracy of all radiologists improved. For benign and malignant lesions, junior radiologists' F1-scores improved to 0.936-0.946 and 0.667-0.680 respectively, while seniors improved to 0.950-0.961 and 0.679-0.753. Additionally, in a triage study of 13,192 consecutive patients, LiAIDS automatically classified 76.46% of patients as low risk with a high NPV of 99.0%. The evidence suggests that LiAIDS can serve as a routine diagnostic tool and enhance the diagnostic capabilities of radiologists for liver lesions.

Comparing the effects and mechanisms of exposure to polystyrene nanoplastics with different functional groups on the male reproductive system.

After aging in the environment, some nanoplastics will carry different charges and functional groups, thereby altering their toxicological effects. To evaluate the potential impact of aging of nanoplastics on the mammalian reproductive system, we exposed C57BL/6 male mice to a dose of 5 mg/kg/d polystyrene nanoparticles (PS-NPs) with different functional groups (unmodified, carboxyl functionalized and amino functionalized) for 45 days for this study. The results suggest that PS-NPs with different functional groups triggered oxidative stress, a decreased in the testis index, disruption of the outer wall of the seminiferous tubules, reduction in the number of spermatogonia cells and sperm counts, and an increased in sperm malformations. We performed GO and KEGG enrichment analysis on the differentially expressed proteins, and found they were mainly enriched in protein transport, RNA splicing and mTOR signaling. We confirmed that the PI3K-AKT-mTOR pathway is over activated, which may lead to reduction of spermatogonia stem cells by over differentiation. Strikingly, PS-NPs with functional group modifications are more toxic than those of unmodified polystyrene, and that PS-NPs with positively charged amino modifications are the most toxic. This study provides a new understanding for correctly evaluating the toxicological effects of plastic aging, and of the mechanism responsible for the reproductive toxicity caused by nanoplastics.

ASPSCR1-TFE3 reprograms transcription by organizing enhancer loops around hexameric VCP/p97.

The t(X,17) chromosomal translocation, generating the ASPSCR1::TFE3 fusion oncoprotein, is the singular genetic driver of alveolar soft part sarcoma (ASPS) and some Xp11-rearranged renal cell carcinomas (RCCs), frustrating efforts to identify therapeutic targets for these rare cancers. Here, proteomic analysis identifies VCP/p97, an AAA+ ATPase with known segregase function, as strongly enriched in co-immunoprecipitated nuclear complexes with ASPSCR1::TFE3. We demonstrate that VCP is a likely obligate co-factor of ASPSCR1::TFE3, one of the only such fusion oncoprotein co-factors identified in cancer biology. Specifically, VCP co-distributes with ASPSCR1::TFE3 across chromatin in association with enhancers genome-wide. VCP presence, its hexameric assembly, and its enzymatic function orchestrate the oncogenic transcriptional signature of ASPSCR1::TFE3, by facilitating assembly of higher-order chromatin conformation structures demonstrated by HiChIP. Finally, ASPSCR1::TFE3 and VCP demonstrate co-dependence for cancer cell proliferation and tumorigenesis in vitro and in ASPS and RCC mouse models, underscoring VCP's potential as a novel therapeutic target.

Ligand-controlled exposure of active sites on the Pd1Ag14 nanocluster surface to boost electrocatalytic CO2 reduction.

Advancing catalyst design requires meticulous control of nanocatalyst selectivity at the atomic level. Here, we synthesized two Pd1Ag14 nanoclusters: Pd1Ag14(PPh3)8(SPh(CF3)2)6 and Pd1Ag14(P(Ph-p-OMe)3)7(SPh)6, each with well-defined structures. Notably, in Pd1Ag14(P(Ph-p-OMe)3)7(SPh)6, the detachment of a phosphine ligand from the top silver atom facilitates the exposure of singular active sites. This exposure significantly enhances its selectivity for the electrocatalytic reduction of CO2 to CO, achieving a Faraday efficiency of 83.3% at -1.3 V, markedly surpassing the 28.1% performance at -1.2 V of Pd1Ag14(PPh3)8(SPh(CF3)2)6. This work underscores the impact of atomic-level structural manipulation on enhancing nanocatalyst performance.

A novel miniature flexible robotic system for endoscopic mucosal dissection: an animal experimental study.

Endoscopic submucosal dissection (ESD) is a standard treatment for early gastrointestinal cancer due to its higher rate of en-bloc resection and lower recurrence rate. However, the technical challenges lead to long learning curve and high risks of adverse events. A gastrointestinal flexible robotic-tool system (GIFTS) was proposed to reduce the difficulty and shorten the learning curve of novices. This is an animal study to evaluate the feasibility of GIFTS in ESD. The GIFTS provides a total of 13 degrees of freedom within 10 mm in diameter and variable stiffness function to achieve endoscopic intervention and submucosal dissection with the cooperation of two flexible robotic instruments. One esophageal and four colorectal ESDs in five porcine models were performed. In all five ESD procedures, the GIFTS was successfully intubated and submucosal dissection was completed without perforation or significant bleeding, and there was no system fault. The mean operative time was 99 min, and the mean size of the specimen was 151 mm2. The fifth experiment showed significantly better results than the first one. In vivo animal experiments confirmed the feasibility of GIFTS in performing ESD. The control of GIFTS is friendly to inexperienced beginners, which will help reduce the technical challenges of ESD and shorten the learning curve of endoscopists.

Research trends and frontier hotspots of TRPV1 based on bibliometric and visualization analyses.

Background: Transient receptor potential vanilloid type1 (TRPV1) is a non-selective cation channel with multiple activation mechanisms, which has received increasing attention since it was first cloned in 1997. Methods: We used bibliometric and visualization analyses to evaluate the theme trends and knowledge structure of TRPV1 research-papers on TRPV1 from 2002 to 2022 obtained from the Web of Science Core Collection. VOSviewer and CiteSpace were used to analyze authors, institutions, countries, co-cited references, and keywords. Results: A total of 7413 papers were included. The main research area of TRPV1 was neuroscience; the most published country was the United States, and the University of California, San Francisco, had the highest centrality. Two major collaborative sub-networks were formed between the authors. The distribution of keywords shows that TRPV1 was initially studied extensively, and the recent studies focused on TRPV1 structure and diseases. "Oxidative stress," "TRPV1 structure," "cancer," and "model" have been the research hotspots in recent years. Conclusions: This research provides valuable information for the study of TRPV1. Disease research was focused on pain, cancer, and neurodegenerative diseases. Both agonists and antagonists of TRPV1 are gradually being used in clinical practice, and acupuncture was effective in treating TRPV1-mediated inflammatory pain. TRPV1 is involved in classical endogenous cannabis system signaling, and new signaling pathways continue to be revealed.

Regulating Crystal Orientation via Ligand Anchoring Enables Efficient Wide-Bandgap Perovskite Solar Cells and Tandems.

Wide-bandgap (WBG) perovskite solar cells have attracted considerable interest for their potential applications in tandem solar cells. However, the predominant obstacles impeding their widespread adoption are substantial open-circuit voltage (VOC ) deficit and severe photo-induced halide segregation. To tackle these challenges, a crystal orientation regulation strategy by introducing dodecyl-benzene-sulfonic-acid as an additive in perovskite precursors is proposed. This method significantly promotes the desired crystal orientation, passivates defects, and mitigates photo-induced halide phase segregation in perovskite films, leading to substantially reduced nonradiative recombination, minimized VOC deficits, and enhanced operational stability of the devices. The resulting 1.66 eV bandgap methylamine-free perovskite solar cells achieve a remarkable power conversion efficiency (PCE) of 22.40% (certified at 21.97%), with the smallest VOC deficit recorded at 0.39 V. Furthermore, the fabricated semitransparent WBG devices exhibit a competitive PCE of 20.13%. Consequently, four-terminal tandem cells comprising WBG perovskite top cells and 1.25 eV bandgap perovskite bottom cells showcase an impressive PCE of 28.06% (stabilized 27.92%), demonstrating great potential for efficient multijunction tandem solar cell applications.

Mesenchymal stem cell-derived exosomes in myocardial infarction: Therapeutic potential and application.

Myocardial infarction refers to the irreversible impairment of cardiac function resulting from the permanent loss of numerous cardiomyocytes and the formation of scar tissue. This condition is caused by acute and persistent inadequate blood supply to the heart's arteries. In the treatment of myocardial infarction, Mesenchymal stem cells (MSCs) play a crucial role because of their powerful therapeutic effects. These effects primarily stem from the paracrine secretion of multiple factors by MSCs, with exosome-carried microRNAs being the most effective component in promoting cardiac function recovery after infarction. Exosome therapy has emerged as a promising cell-free treatment for myocardial infarction as a result of its relatively simple composition, low immunogenicity and controlled transplantation dose. Despite these advantages, maintaining the stability of exosomes after transplantation and enhancing their targeting effect remain significant challenges in clinical applications. In recent developments, several approaches have been designed to optimize exosome therapy. These include enhancing exosome retention, improving their ability to target specific effects, pretreating MSC-derived exosomes and employing transgenic MSC-derived exosomes. This review primarily focuses on describing the biological characteristics of exosomes, their therapeutic potential and their application in treating myocardial infarction.

A Novel Extensible Continuum Robot with Growing Motion Capability Inspired by Plant Growth for Path-Following in Transoral Laryngeal Surgery.

This article presents a novel extensible continuum robot (ECR) with growing motion capability for improved flexible access in transoral laryngeal procedures. The robot uses an extensible continuum joint with a staggered V-shaped notched structure as the backbone, driven by the pushing and pulling of superelastic Nitinol rods. The notched structure is optimized to achieve a wide range of extension/contraction and bending motion for the continuum joint. The successive and uniform deflection of the notches provides the continuum joint with excellent constant curvature bending characteristics. The bidirectional rod-driven approach expands the robot's extension capabilities with both pushing and pulling operations, and the superelasticity of the driving rods preserves the robot's bending performance. The ECR significantly increases motion dexterity and reachability through its variable length, which facilitates collision-free access to deep lesions by following the anatomy. To further exploit the advantages of the ECR in path-following for flexible access, a growing motion approach inspired by the plant growth process has been proposed to minimize the path deviation error. Characterization experiments are conducted to verify the performances of the proposed ECR. The extension ratio achieves up to 225.92%, and the average distal positioning error and hysteresis error values are 2.87% and 0.51% within the ±120° bending range. Compared with the typical continuum robot with a fixed length, the path-following deviation of this robot is reduced by more than 58.30%, effectively reducing the risk of collision during access. Phantom experiments validate the feasibility of the proposed concept in flexible access procedures.

Clinical Characteristics and Prognosis of Biliary Atresia with Low Serum Matrix Metalloproteinase-7 Levels.

PURPOSE: Serum matrix metalloproteinase-7 (MMP-7) levels can precisely differentiate biliary atresia (BA) from non-BA cholestasis. However, serum MMP-7 levels of some BA patients were within normal range or slightly elevated. This study aimed to investigate the clinical characteristics and prognosis of biliary atresia with low serum MMP-7 levels. METHOD: This is a retrospective cohort study. Cases of BA from July 2020 to December 2022 were consecutively enrolled. They were divided into low-MMP-7 group (MMP-7 ≤ 25 ng/ml) and high-MMP-7 group (MMP-7 > 25 ng/ml) according to serum MMP-7 levels preoperatively. The perioperative clinical characteristics, the 3-month and 6-month jaundice clearance rate post-Kasai procedure, and the native liver survival were compared between the two groups. RESULTS: A total of 329 cases were included in this study, 40 of which were divided into the low-MMP-7 group. Preoperative GGT and direct bilirubin levels in the low-MMP-7 group were significantly lower than those in the high-MMP-7 group (258.6 U/L, interquartile range [IQR]: 160.4411.6 vs. 406.8 IU/L, IQR: 215,655.0, P = 0.0076; 103.8 µmol/L, IQR: 79.0,121.4 vs. 115.3 µmol/L, IQR: 94,138.8, P = 0.0071), while the gender, the day at surgery and preoperative ALT, AST, TBA, total bilirubin levels showed no significant differences (P > 0.05). The 3-month and 6-month jaundice clearance rate post-Kasai procedure in the low-MMP-7 group were lower than those in the high-MMP-7 group (29.73% vs. 53.09%, P = 0.049; 32.14% vs. 54.73%, P = 0.023). The 1-year native liver survival rate was 29.63% for the low-MMP-7 group and 53.02% for the high-MMP-7 group (P = 0.022). CONCLUSION: Preoperative clinical characteristics were similar between low-MMP-7 group and high-MMP-7 group, while patients with low serum MMP-7 levels showed worse prognosis, indicating that this might be listed as a new clinical subtype of BA which could contribute to designing new treatment strategies for BA in the future. STUDY TYPE: Cohort Study. LEVEL OF EVIDENCE: Level II.

Surface Microstructure Engineering in MAPbBr3 Microsheets for Performance-Enhanced Photodetectors.

Metal halide-perovskite-based photodetectors have recently emerged as a class of promising optoelectronic devices in various fields. Meanwhile, nano/microstructuring perovskite-based photodetectors are a facile integration with complementary metal-oxide semiconductors for miniaturized imaging systems. However, there are still challenges to be overcome in reducing the losses caused by light reflection on the surface of microstructural perovskites. In this work, surface microstructure engineering is employed in MAPbBr3 microsheets for reducing light reflection and improving light absorption, resulting in high-performance perovskite photodetectors. MAPbBr3 microsheets, which possess different surface morphologies of flat, upright hemisphere arrays and inverted hemisphere arrays (IHAs), are fabricated by a simple microstructure template-assisted space confinement process. The light absorption capacity of IHA MAPbBr3 is significantly higher than that of the other two structures. Hence, IHA photodetectors with excellent figures of merit, including low dark current, decent responsivity, and fast speed, are achieved. Furthermore, the noise of the IHA photodetectors is only ∼10-13 A/Hz, which results in the superior sensitivity for weak light detection with a specific detectivity up to 1011 Jones. Our results demonstrate that surface engineering is a simple, low-cost, yet effective approach to improve the performance of nano-/micro-optoelectronic devices.

Constructing perfect cubic Ag-Cu alloyed nanoclusters through selective elimination of phosphine ligands.

The aspiration of chemists has always been to design and achieve control over nanoparticle morphology at the atomic level. Here, we report a synthesis strategy and crystal structure of a perfect cubic Ag-Cu alloyed nanocluster, [Ag55Cu8I12(S-C6H32,4(CH3)2)24][(PPh4)] (Ag55Cu8I12 for short). The structure of this cluster was determined by single-crystal X-ray diffraction (SCXRD) and further validated by X-ray photoelectron spectroscopy (XPS), inductively coupled plasma (ICP), Energy-dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), and 1H and 31P nuclear magnetic resonance (NMR). The surface deviation of the cube was measured to be 0.291 Å, making it the flattest known cube to date.