Allergen protease-activated stress granule assembly and gasdermin D fragmentation control interleukin-33 secretion.

Interleukin-33 (IL-33), an epithelial cell-derived cytokine that responds rapidly to environmental insult, has a critical role in initiating airway inflammatory diseases. However, the molecular mechanism underlying IL-33 secretion following allergen exposure is not clear. Here, we found that two cell events were fundamental for IL-33 secretion after exposure to allergens. First, stress granule assembly activated by allergens licensed the nuclear-cytoplasmic transport of IL-33, but not the secretion of IL-33. Second, a neo-form murine amino-terminal p40 fragment gasdermin D (Gsdmd), whose generation was independent of inflammatory caspase-1 and caspase-11, dominated cytosolic secretion of IL-33 by forming pores in the cell membrane. Either the blockade of stress granule assembly or the abolishment of p40 production through amino acid mutation of residues 309-313 (ELRQQ) could efficiently prevent the release of IL-33 in murine epithelial cells. Our findings indicated that targeting stress granule disassembly and Gsdmd fragmentation could reduce IL-33-dependent allergic airway inflammation.

Free-space dissemination of time and frequency with 10-19 instability over 113 km.

Networks of optical clocks find applications in precise navigation1,2, in efforts to redefine the fundamental unit of the 'second'3-6 and in gravitational tests7. As the frequency instability for state-of-the-art optical clocks has reached the 10-19 level8,9, the vision of a global-scale optical network that achieves comparable performances requires the dissemination of time and frequency over a long-distance free-space link with a similar instability of 10-19. However, previous attempts at free-space dissemination of time and frequency at high precision did not extend beyond dozens of kilometres10,11. Here we report time-frequency dissemination with an offset of 6.3 × 10-20 ± 3.4 × 10-19 and an instability of less than 4 × 10-19 at 10,000 s through a free-space link of 113 km. Key technologies essential to this achievement include the deployment of high-power frequency combs, high-stability and high-efficiency optical transceiver systems and efficient linear optical sampling. We observe that the stability we have reached is retained for channel losses up to 89 dB. The technique we report can not only be directly used in ground-based applications, but could also lay the groundwork for future satellite time-frequency dissemination.

Structural Regulation of Covalent Organic Frameworks for Catalysis.

ConspectusChemical reactions can be promoted at lower temperatures and pressures, thereby reducing the energy input, by introducing suitable catalysts. Despite its significance, the quest for efficient and stable catalysts remains a significant challenge. In this context, addressing the efficiency of catalysts stands out as a paramount concern. However, the challenges posed by the vague structure and limited tailorability of traditional catalysts would make it highly desirable to fabricate optimized catalysts based on the understanding of structure-activity relationships. Covalent organic frameworks (COFs), a subclass of fully designed crystalline materials formed by the polymerization of organic building blocks through covalent bonds have garnered widespread attention in catalysis. The precise and customizable structures of COFs, coupled with attributes such as high surface area and facile functional modification, make COFs attractive molecular platforms for catalytic applications. These inherent advantages position COFs as ideal catalysts, facilitating the elucidation of structure-performance relationships and thereby further improving the catalysis. Nevertheless, there is a lack of systematic emphasis on and summary of structural regulation at the atomic/molecular level for COF catalysis. Consequently, there is a growing need to summarize this research field and provide deep insights into COF-based catalysis to promote its further development.In this Account, we will summarize recent advances in structural regulation achieved in COF-based catalysts, placing an emphasis on the molecular design of the structures for enhanced catalysis. Considering the unique components and structural advantages of COFs, we present the fundamental principles for the rational design of structural regulation in COF-based catalysis. This Account starts by presenting an overview of catalysis and explaining why COFs are promising catalysts. Then, we introduce the molecular design principle for COF catalysis. Next, we present the following three aspects of the specific strategies for structural regulation of COF-based catalysts: (1) By designing different functional groups and integrating metal species into the organic unit, the activity and/or selectivity can be finely modulated. (2) Regulating the linkage facilitates charge transfer and/or modulates the electronic structure of catalytic metal sites, and accordingly, the intrinsic activity/selectivity can be further improved. (3) By means of pore wall/space engineering, the microenvironment surrounding catalytic metal sites can be modulated to optimize performance. Finally, the current challenges and future developments in the structural regulation of COF-based catalysts are discussed in detail. This Account provides insight into the structural regulation of COF-based catalysts at the atomic/molecular level toward improving their performance, which would provide significant inspiration for the design and structural regulation of other heterogeneous catalysts.

Metal-organic frameworks for organic transformations by photocatalysis and photothermal catalysis.

Organic transformation by light-driven catalysis, especially, photocatalysis and photothermal catalysis, denoted as photo(thermal) catalysis, is an efficient, green, and economical route to produce value-added compounds. In recent years, owing to their diverse structure types, tunable pore sizes, and abundant active sites, metal-organic framework (MOF)-based photo(thermal) catalysis has attracted broad interest in organic transformations. In this review, we provide a comprehensive and systematic overview of MOF-based photo(thermal) catalysis for organic transformations. First, the general mechanisms, unique advantages, and strategies to improve the performance of MOFs in photo(thermal) catalysis are discussed. Then, outstanding examples of organic transformations over MOF-based photo(thermal) catalysis are introduced according to the reaction type. In addition, several representative advanced characterization techniques used for revealing the charge reaction kinetics and reaction intermediates of MOF-based organic transformations by photo(thermal) catalysis are presented. Finally, the prospects and challenges in this field are proposed. This review aims to inspire the rational design and development of MOF-based materials with improved performance in organic transformations by photocatalysis and photothermal catalysis.

Modulating the Primary and Secondary Coordination Spheres of Single Ni(II) Sites in Metal-Organic Frameworks for Boosting Photocatalysis.

Though the coordination environment of single metal sites has been recognized to be of great importance in promoting catalysis, the influence of simultaneous precise modulation of primary and secondary coordination spheres on catalysis remains largely unknown. Herein, a series of single Ni(II) sites with altered primary and secondary coordination spheres have been installed onto metal-organic frameworks (MOFs) with UiO-67 skeleton, affording UiO-Ni-X-Y (X = S, O; Y = H, Cl, CF3) with X and Y on the primary and secondary coordination spheres, respectively. Upon deposition with CdS nanoparticles, the resulting composites present high photocatalytic H2 production rates, in which the optimized CdS/UiO-Ni-S-CF3 exhibits an excellent activity of 13.44 mmol g-1, ∼500 folds of the pristine catalyst (29.6 µmol g-1 for CdS/UiO), in 8 h, highlighting the key role of microenvironment modulation around Ni sites. Charge kinetic analysis and theoretical calculation results demonstrate that the charge transfer dynamics and reaction energy barrier are closely correlated with their coordination spheres. This work manifests the advantages of MOFs in the fabrication of structurally precise catalysts and the elucidation of particular influences of microenvironment modulation around single metal sites on the catalytic performance.

Bottom-Up Construction of Metal-Organic Framework Loricae on Metal Nanoclusters with Consecutive Single Nonmetal Atom Tuning for Tailored Catalysis.

The introduction of single or multiple heterometal atoms into metal nanoparticles is a well-known strategy for altering their structures (compositions) and properties. However, surface single nonmetal atom doping is challenging and rarely reported. For the first time, we have developed synthetic methods, realizing "surgery"-like, successive surface single nonmetal atom doping, replacement, and addition for ultrasmall metal nanoparticles (metal nanoclusters, NCs), and successfully synthesized and characterized three novel bcc metal NCs Au38I(S-Adm)19, Au38S(S-Adm)20, and Au38IS(S-Adm)19 (S-Adm: 1-adamantanethiolate). The influences of single nonmetal atom replacement and addition on the NC structure and optical properties (including absorption and photoluminescence) were carefully investigated, providing insights into the structure (composition)-property correlation. Furthermore, a bottom-up method was employed to construct a metal-organic framework (MOF) on the NC surface, which did not essentially alter the metal NC structure but led to the partial release of surface ligands and stimulated metal NC activity for catalyzing p-nitrophenol reduction. Furthermore, surface MOF construction enhanced NC stability and water solubility, providing another dimension for tunning NC catalytic activity by modifying MOF functional groups.

Manipulating the Spin State of Co Sites in Metal-Organic Frameworks for Boosting CO2 Photoreduction.

Photocatalytic CO2 reduction holds great potential for alleviating global energy and environmental issues, where the electronic structure of the catalytic center plays a crucial role. However, the spin state, a key descriptor of electronic properties, is largely overlooked. Herein, we present a simple strategy to regulate the spin states of catalytic Co centers by changing their coordination environment by exchanging the Co species into a stable Zn-based metal-organic framework (MOF) to afford Co-OAc, Co-Br, and Co-CN for CO2 photoreduction. Experimental and DFT calculation results suggest that the distinct spin states of the Co sites give rise to different charge separation abilities and energy barriers for CO2 adsorption/activation in photocatalysis. Consequently, the optimized Co-OAc with the highest spin-state Co sites presents an excellent photocatalytic CO2 activity of 2325.7 µmol·g-1·h-1 and selectivity of 99.1% to CO, which are among the best in all reported MOF photocatalysts, in the absence of a noble metal and additional photosensitizer. This work underlines the potential of MOFs as an ideal platform for spin-state manipulation toward improved photocatalysis.

Introducing Hydrogen-Bonding Microenvironment in Close Proximity to Single-Atom Sites for Boosting Photocatalytic Hydrogen Production.

Inspired by enzymatic catalysis, it is crucial to construct hydrogen-bonding-rich microenvironment around catalytic sites; unfortunately, its precise construction and understanding how the distance between such microenvironment and catalytic sites affects the catalysis remain significantly challenging. In this work, a series of metal-organic framework (MOF)-based single-atom Ru1 catalysts, namely, Ru1/UiO-67-X (X = -H, -m-(NH2)2, -o-(NH2)2), have been synthesized, where the distance between the hydrogen-bonding microenvironment and Ru1 sites is modulated by altering the location of amino groups. The -NH2 group can form hydrogen bonds with H2O, constituting a unique microenvironment that causes an increased water concentration around the Ru1 sites. Remarkably, Ru1/UiO-67-o-(NH2)2 displays a superior photocatalytic hydrogen production rate, ∼4.6 and ∼146.6 times of Ru1/UiO-67-m-(NH2)2 and Ru1/UiO-67, respectively. Both experimental and computational results suggest that the close proximity of amino groups to the Ru1 sites in Ru1/UiO-67-o-(NH2)2 improves charge transfer and H2O dissociation, accounting for the promoted photocatalytic hydrogen production.

SMYD4 monomethylates PRMT5 and forms a positive feedback loop to promote hepatocellular carcinoma progression.

Both lysine and arginine methyltransferases are thought to be promising therapeutic targets for malignant tumors, yet how these methyltransferases function in malignant tumors, especially hepatocellular carcinoma (HCC), has not been fully elucidated. Here, we reported that SMYD4, a lysine methyltransferase, acts as an oncogene in HCC. SMYD4 was highly upregulated in HCC and promoted HCC cell proliferation and metastasis. Mechanistically, PRMT5, a well-known arginine methyltransferase, was identified as a SMYD4-binding protein. SMYD4 monomethylated PRMT5 and enhanced the interaction between PRMT5 and MEP50, thereby promoting the symmetrical dimethylation of H3R2 and H4R3 on the PRMT5 target gene promoter and subsequently activating DVL3 expression and inhibiting expression of E-cadherin, RBL2, and miR-29b-1-5p. Moreover, miR-29b-1-5p was found to inversely regulate SMYD4 expression in HCC cells, thus forming a positive feedback loop. Furthermore, we found that the oncogenic effect of SMYD4 could be effectively suppressed by PRMT5 inhibitor in vitro and in vivo. Clinically, high coexpression of SMYD4 and PRMT5 was associated with poor prognosis of HCC patients. In summary, our study provides a model of crosstalk between lysine and arginine methyltransferases in HCC and highlights the SMYD4-PRMT5 axis as a potential therapeutic target for the treatment of HCC.

Expected Eight-Week Prenatal Versus Twelve-Week Perinatal Tenofovir Alafenamide Prophylaxis to Prevent Mother-To-Child Transmission of Hepatitis B Virus: A Multicenter, Prospective, Open-label, Randomized Controlled Trial.

INTRODUCTION: The course of maternal antiviral prophylaxis to prevent mother-to-child transmission of hepatitis B virus (HBV-MTCT) varies greatly, and it has not been demonstrated in a randomized controlled study. METHODS: In this multicenter, open-label, randomized controlled trial, eligible pregnant women with HBV DNA of 5.3-9.0 log10 IU/mL who received tenofovir alafenamide fumarate (TAF) from the first day of 33 gestational weeks to delivery (expected eight-week) or to four-week postpartum (expected twelve-week) were randomly enrolled at a 1:1 ratio and followed until six-month postpartum. All infants received standard immunoprophylaxis (hepatitis B immunoglobulin and vaccine). The primary endpoint was the safety of mothers and infants. The secondary endpoint was infants' HBV-MTCT rate at seven months of age. RESULTS: Among 119 and 120 intention-to-treat pregnant women, 115 and 116 women were followed until delivery, and 110 and 112 per-protocol mother-infant dyads in two groups completed the study. Overall, TAF was well tolerated, no one discontinued therapy due to adverse events (0/239, 0%, 95% confidence interval [CI] 0%-1.6%), and no infant had congenital defects or malformations at delivery (0/231, 0%, 95% CI 0%-1.6%). The infants' physical development at birth (n=231) and at seven months (n=222) were normal. Furthermore, 97.0% (224/231, 95% CI 93.9%-98.5%) of women achieved HBV DNA <5.3 log10 IU/mL at delivery. The intention-to-treat and per-protocol infants' HBV-MTCT rates were 7.1% (17/239, 95% CI 4.5%-11.1%) and 0% (0/222, 95% CI 0%-1.7%) at seven months of age. Comparatively, 15.1% (18/119, 95% CI 9.8%-22.7%) versus 18.3% (22/120, 95% CI 12.4%-26.2%) of women in the two groups had mildly elevated alanine aminotransferase levels at three-month and six-month postpartum, respectively (P=0.507); notably, no one experienced alanine aminotransferase flare (0% [0/119, 95% CI 0%-3.1%] versus 0% [0/120, 0%-3.1%]). DISCUSSION: Maternal TAF prophylaxis to prevent HBV-MTCT is generally safe and effective, and expected eight-week prenatal duration is feasible. ClinicalTrials.gov, NCT04850950.

Identification of a novel LFNG variant in a Chinese fetus with spondylocostal dysostosis and a systematic review.

Spondylocostal dysostosis (SCDO) encompasses a group of skeletal disorders characterized by multiple segmentation defects in the vertebrae and ribs. SCDO has a complex genetic etiology. This study aimed to analyze and identify pathogenic variants in a fetus with SCDO. Copy number variant sequencing and whole exome sequencing were performed on a Chinese fetus with SCDO, followed by bioinformatics analyses, in vitro functional assays and a systematic review on the reported SCDO cases with LFNG pathogenic variants. Ultrasound examinations in utero exhibited that the fetus had vertebral malformation, scoliosis and tethered cord, but rib malformation was not evident. We found a novel homozygous variant (c.1078 C > T, p.R360C) within the last exon of LFNG. The variant was predicted to cause loss of function of LFNG by in silico prediction tools, which was confirmed by an in vitro assay of LFNG enzyme activity. The systematic review listed a total of 20 variants of LFNG in SCDO. The mutational spectrum spans across all exons of LFNG except the last one. This study reported the first Chinese case of LFNG-related SCDO, revealing the prenatal phenotypes and expanding the mutational spectrum of the disorder.

Non-Line-of-Sight Imaging and Vibrometry Using a Comb-Calibrated Coherent Sensor.

Non-line-of-sight (NLOS) imaging has the ability to reconstruct hidden objects, allowing a wide range of applications. Existing NLOS systems rely on pulsed lasers and time-resolved single-photon detectors to capture the information encoded in the time of flight of scattered photons. Despite remarkable advances, the pulsed time-of-flight LIDAR approach has limited temporal resolution and struggles to detect the frequency-associated information directly. Here, we propose and demonstrate the coherent scheme-frequency-modulated continuous wave calibrated by optical frequency comb-for high-resolution NLOS imaging, velocimetry, and vibrometry. Our comb-calibrated coherent sensor presents a system temporal resolution at subpicosecond and its superior signal-to-noise ratio permits NLOS imaging of complex scenes under strong ambient light. We show the capability of NLOS localization and 3D imaging at submillimeter scale and demonstrate NLOS vibrometry sensing at an accuracy of dozen Hertz. Our approach unlocks the coherent LIDAR techniques for widespread use in imaging science and optical sensing.

A hsa_circ_001726 axis regulated by E2F6 contributes to metastasis of hepatocellular carcinoma.

BACKGROUND: CircRNAs participate in the development of hepatocellular carcinoma (HCC). This work aims to explore the key tumor promoting circRNA as a gene therapy target. METHODS: The differentially expressed gene circRNAs in HCC tumor tissues was identified by mining GSE121714 dataset. EdU staining, wound healing, transwell invasion assay, TUNEL staining and western blotting examined proliferation, migration, invasion, apoptosis and epithelial mesenchymal transition (EMT). Xenograft mouse model and orthotopic transplantation tumor mouse model were constructed to verify the role of hsa_circ_001726 in growth and metastasis of HCC. The relationship among CCT2, E2F6, hsa_circ_001726, miR-671-5p and PRMT9 was identified by RNA-fluorescence in situ hybridization, luciferase reporter assay and RNA Immunoprecipitation. RESULTS: Eleven differentially expressed circRNAs were found in HCC tumors. Among them, hsa_circ_001726 was highly expressed in HCC tumors and cells, which was transcribed from CCT2. As a transcription factor of CCT2, E2F6 knockdown inactivated CCT2 promoter and reduced hsa_circ_001726 expression. Moreover, hsa_circ_001726 elevated PRMT9 expression by sponging miR-671-5p, and then activated Notch signaling pathway. Additionally, hsa_circ_001726 deficiency repressed malignant phenotypes of HCC cells, including proliferation, migration, invasion, EMT and apoptosis. In vivo, hsa_circ_001726 deficiency reduced tumor growth and lung metastasis of HCC in xenograft mouse models and orthotopic transplantation tumor mouse models. CONCLUSION: Hsa_circ_001726 functioned as an oncogene in HCC, which was derived from CCT2 and regulated by E2F6. Hsa_circ_001726 elevated PRMT9 expression by sponging miR-671-5p, and then activated Notch signaling pathway, thereby accelerating malignant phenotypes of HCC. Therefore, targeting hsa_circ_001726 may be a new avenue for HCC treatment.

Nesfatin-1 enhances vascular smooth muscle calcification through facilitating BMP-2 osteogenic signaling.

Vascular calcification (VC) arises from the accumulation of calcium salts in the intimal or tunica media layer of the aorta, contributing to higher risk of cardiovascular events and mortality. Despite this, the mechanisms driving VC remain incompletely understood. We previously described that nesfatin-1 functioned as a switch for vascular smooth muscle cells (VSMCs) plasticity in hypertension and neointimal hyperplasia. In this study, we sought to investigate the role and mechanism of nesfatin-1 in VC. The expression of nesfatin-1 was measured in calcified VSMCs and aortas, as well as in patients. Loss- and gain-of-function experiments were evaluated the roles of nesfatin-1 in VC pathogenesis. The transcription activation of nesfatin-1 was detected using a mass spectrometry. We found higher levels of nesfatin-1 in both calcified VSMCs and aortas, as well as in patients with coronary calcification. Loss-of-function and gain-of-function experiments revealed that nesfatin-1 was a key regulator of VC by facilitating the osteogenic transformation of VSMCs. Mechanistically, nesfatin-1 promoted the de-ubiquitination and stability of BMP-2 via inhibiting the E3 ligase SYTL4, and the interaction of nesfatin-1 with BMP-2 potentiated BMP-2 signaling and induced phosphorylation of Smad, followed by HDAC4 phosphorylation and nuclear exclusion. The dissociation of HDAC4 from RUNX2 elicited RUNX2 acetylation and subsequent nuclear translocation, leading to the transcription upregulation of OPN, a critical player in VC. From a small library of natural compounds, we identified that Curculigoside and Chebulagic acid reduced VC development via binding to and inhibiting nesfatin-1. Eventually, we designed a mass spectrometry-based DNA-protein interaction screening to identify that STAT3 mediated the transcription activation of nesfatin-1 in the context of VC. Overall, our study demonstrates that nesfatin-1 enhances BMP-2 signaling by inhibiting the E3 ligase SYTL4, thereby stabilizing BMP-2 and facilitating the downstream phosphorylation of SMAD1/5/9 and HDAC4. This signaling cascade leads to RUNX2 activation and the transcriptional upregulation of MSX2, driving VC. These insights position nesfatin-1 as a potential therapeutic target for preventing or treating VC, advancing our understanding of the molecular mechanisms underlying this critical cardiovascular condition.

One-Pot Synthesis of C@BiOBr for Efficient Photocatalytic Degradation of Phenol.

This work describes the synthesis of C@BiOBr using glucose as the carbon precursor by a repeatable one-step hydrothermal method. Characterization studies indicate that the structure of BiOBr did not change after the carbon layer was encapsulated on the surface. The highest activity is achieved at 1.2-C@BiOBr, with 97% of phenol (50 mg·L-1) degrading within 90 min, and the degradation amount of phenol is determined to be 48.5 mg·g-1 with a speed of 0.54 mg·g-1·min-1. The useful species of phenol degradation are studied and assigned to •O2-, 1O2, and h+. The effect of coated carbon layer for photocatalytic degradation of phenol over BiOBr is studied by photoelectrochemical experiments, fluorescence spectra, and density functional theory (DFT) calculations. It is attributed to the good conductivity of carbon, enhanced separation of the photocarriers by carbon coating, and thermodynamically favorable reactive oxygen species (ROS) production on the surface of carbon. This work demonstrates that carbon coating is an effective strategy to improve the photocatalytic activity of BiOBr and reveals the detailed mechanism.

Resveratrol Promotes Diabetic Wound Healing by Inhibiting Notch Pathway.

INTRODUCTION: Diabetic foot ulcer (DFU) is a severe complication that threatens the daily lives of patients with diabetes and represents a serious challenge to the global health system. Considering that impaired wound healing is the leading cause of DFU, exploring the mechanism of diabetic wound healing is beneficial for improving DFU treatment. Resveratrol (RES) is a native polyphenol with various pharmacological characteristics, and recent studies have indicated an accelerated function of RES in diabetic wound healing. As human dermal fibroblasts (HDFs) play a significant role in diabetic wound healing, this study aimed to elucidate the regulatory mechanism of RES in HDFs. METHODS: To mimic diabetic wound healing in vitro, the HDFs were stimulated with high glucose (HG). Our findings revealed that RES reversed HG-induced suppression of HDF proliferation and migration caused by HG. RES inhibits the Notch signaling pathway. More importantly, we demonstrated that the activation of the Notch pathway abrogated the effects of RES on HG-induced HDFs. RESULTS: In vivo assays also illustrated that RES contributed to wound healing in diabetic mice by blocking the Notch pathway. CONCLUSIONS: In conclusion, RES improved diabetic wound healing by targeting the Notch pathway, which offers novel insights into DFU therapy.

Use of 3D Echocardiography Facilitates Analysis of Thrombolytic Efficacy in Patients With Persistent Atrial Fibrillation.

ABSTRACT: This study seeks to identify the anticoagulant efficacy of rivaroxaban treatment on thrombi detected using echocardiography of the left atrial appendage in 275 patients with persistent atrial fibrillation. During follow-up after 9-24 weeks of rivaroxaban treatment, patients were divided into "effective group" (n = 143) and "ineffective group" (n = 132) according to the thrombolytic effect of the drug. Left atrial diameter (LAD), left atrial ejection fraction (LAEF), left ventricular ejection fraction (LVEF), mean diameter of left atrial appendage (LAAD mean ), angle between left atrial appendage and left atrium (LAA-A), velocity of blood flow in left atrial appendage (LAA-v), and thrombus size were compared before and after drug administration. Following treatment, LAEF, LVEF, and LAA-v values were greater and LAD and LAAD mean values were lower in the effective ( P < 0.05). Logistic regression analysis showed significant correlations of LAD, LAEF, LVEF, LAA-A, and LAA-v with anticoagulant efficacy ( P < 0.05). The efficacy of rivaroxaban in treatment of left atrial auricular thrombosis in patients with persistent AF was correlated with LAD, LAEF, LVEF, LAA-A, and LAA-v. Multivariate logistic regression analysis further revealed LAEF [odds ratio (OR) 1.7, 95% confidence interval (CI), 0.45-16.9, P = 0.008], 3D-EF (OR 6.4, 95% CI, 1.06-16.9, P = 0.039) and left ventricular global longitudinal strain (OR 18.0, 95% CI, 1.38-35.68, P = 0.028) as factors related to left atrial appendage thrombus. Echocardiography with global longitudinal strain assessment could be effectively utilized to evaluate the functional parameters of LAA and thus aid in predicting the safety of rivaroxaban as an anticoagulation agent.

Comparison of EUS-FNA and EUS-FNB for diagnosis of solid pancreatic mass lesions: a meta-analysis of prospective studies.

Objective: To quantitatively compare the diagnostic value of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) in solid pancreatic mass lesions using a systematic evaluation method.Methods: A systematic literature search was conducted on public databases to include studies comparing the diagnostic value of EUS-FNA and EUS-FNB in solid pancreatic mass lesions. The combined effect size was estimated using mean difference (MD) and risk difference (RD) respectively, and the corresponding 95% confidence interval (CI) was calculated.Results: The 12 articles (7 RCTs and 5 cohort studies) met the inclusion criteria of this study. The meta-analysis showed that compared with EUS-FNB, EUS-FNA had lower diagnostic accuracy (RD: -0.08, 95% CI: -0.15, -0.01) and specimen adequacy (RD: -0.08, 95% CI: -0.15, -0.02), while higher required number of needle passes (MD: 0.42, 95% CI: 0.12, 0.73). However, EUS-FNB and EUS-FNA presented similar overall complications (RD: 0.00, 95% CI: -0.01, 0.02) and technical failures (RD: -0.01, 95% CI: -0.02, 0.00), without statistically significant differences.Conclusions: Compared with EUS-FNA, EUS-FNB seems to be a better choice for diagnosing suspected pancreatic lesions.

MKK3 depletion attenuates intestinal injury after traumatic hemorrhagic shock by restoring mitochondrial function.

BACKGROUND: Traumatic hemorrhagic shock (THS) is a complex pathophysiological process resulting in multiple organ failure. Intestinal barrier dysfunction is one of the mechanisms implicated in multiple organ failure. The present study aimed to explore the regulatory role of mitogen-activated protein kinase kinase 3 (MKK3) in THS-induced intestinal injury and to elucidate its potential mechanism. METHODS: Rats were subjected to trauma and hemorrhage to establish a THS animal model. MKK3-targeted lentiviral vectors were injected via the tail vein 72 h before modeling. Twelve hours post-modeling, the mean arterial pressure (MAP) and heart rate (HR) were monitored, and histological injury to the intestine was assessed via H&E staining and transmission electron microscopy. Mitochondrial function and mitochondrial reactive oxygen species (ROS) were evaluated. IEC-6 cells were exposed to hypoxia to mimic intestinal injury following THS in vitro. RESULTS: MKK3 deficiency alleviated intestinal injury and restored mitochondrial function in intestinal tissues from THS-induced rats and hypoxia-treated IEC-6 cells. In addition, MKK3 deficiency promoted Sirt1/PGC-1α-mediated mitochondrial biogenesis and restricted Pink1/Parkin-mediated mitophagy in the injured intestine and IEC-6 cells. Furthermore, the protective effect of MKK3 knockdown against hypoxia-induced mitochondrial damage was strengthened upon simultaneous LC3B/Pink1/Parkin knockdown or weakened upon simultaneous Sirt1 knockdown. CONCLUSION: MKK3 deficiency protected against intestinal injury induced by THS by promoting mitochondrial biogenesis and restricting excessive mitophagy.

Antidepressant use and the risk of seizure: a meta-analysis of observational studies.

PURPOSE: The association between antidepressant use and the risk of seizures remains controversial. Therefore, this meta-analysis examined whether antidepressant use affects the risk of seizures. METHODS: To identify relevant observational studies, we conducted systematic searches in PubMed and Embase of studies published through May 2023. Random-effects models were used to estimate overall relative risk. RESULTS: Our meta-analysis included eight studies involving 1,709,878 individuals. Our results showed that selective serotonin reuptake inhibitors (SSRI) (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.32-1.66; P < 0.001) and selective noradrenalin reuptake inhibitors (SNRI) (OR 1.65, 95% CI 1.24-2.19; P = 0.001), but not tricyclic antidepressants (TCA) (OR 1.27, 95% CI 0.84-1.92; P = 0.249), were associated with an increased risk of seizures. Subgroup analyses revealed an OR of 2.35 (95% CI 1.7, 3.24; P < 0.001) among short-term (< 30 days) antidepressant users. CONCLUSIONS: The findings of this meta-analysis support an increased risk of seizures in new-generation antidepressant users, expanding previous knowledge by demonstrating a more pronounced risk in short-term users.