Photocatalytic One-Pot Three-Component Reaction for the Regioselective Synthesis of Bromo-Substituted Pyrazoles.

A photocatalytic three-component cascade reaction of readily available enaminones, hydrazines, and CBr4 for the synthesis of bromo-substituted pyrazoles in one pot has been demonstrated. This strategy involves intermolecular C-N/C-Br bond formation and represents an efficient approach to the construction of 4-bromo-substituted pyrazoles with high regioselectivity, broad substrate scope, good functional group tolerance, convenient operation, and mild reaction conditions. Mechanistic investigations show that this reaction proceeds via intermolecular cyclization of enaminones with hydrazines, followed by a regioselective bromination of pyrazoles using CBr4 as a "Br" source.

Mesoscale eddy in situ observation and characterization via underwater glider and complex network theory.

Mesoscale eddies have attracted increased attention due to their central role in ocean energy and mass transport. The observations of their three-dimensional structure will facilitate the understanding of nonlinear eddy dynamics. In this paper, we propose a novel framework, the mesoscale eddy characterization from ordinal modalities recurrence networks method (MeC-OMRN), that utilizes a Petrel-II underwater glider for in situ observations and vertical structure characterization of a moving mesoscale eddy in the northern South China Sea. First, higher resolution continuous observation profile data collected throughout the traversal by the underwater glider are acquired and preprocessed. Subsequently, we analyze and compute these nonlinear data. To further amplify the hidden structural features of the mesoscale eddy, we construct ordinal modalities sequences rich in spatiotemporal characteristics based on the measured vertical density of the mesoscale eddy. Based on this, we employ ordinal modalities recurrence plots (OMRPs) to depict the vertical structure inside and outside the eddy, revealing significant differences in the OMRPs and the unevenness of density stratification within the eddy. To validate our intriguing findings from the perspective of complex network theory, we build the multivariate weighted ordinal modalities recurrence networks, through which network measures exhibit a more random distribution of vertical density stratification within the eddy, possibly due to more intense vertical convection and oscillations within the eddy's seawater micelles. These framework and intriguing findings are anticipated to be applied to more data-driven in situ observation tasks of oceanic phenomena.

Risk Factors of Postoperative Atrial Fibrillation After Isolated Coronary Artery Bypass Grafting Surgery in the Recent 10 Years: Clinical Analysis of 6229 Patients.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication after coronary artery bypass grafting (CABG) that prolongs hospitalization and increases expenses. HYPOTHESIS: Perioperative risk factors may predict POAF. METHODS: From March 2015 to January 2023, 6229 patients who underwent isolated CABG and were in sinus rhythm before CABG were included in this retrospective study. The preoperative and postoperative variants of patients were collected and analyzed by univariate analyses between the patients with and without POAF. Multivariate logistic regression analysis was then used to study the independent risk factors for POAF. RESULTS: The incidence of POAF in this group of patients was 30.94%. Univariate analyses demonstrated that age (p < 0.001), hypertension (p < 0.001), smoking (p < 0.05), cardiopulmonary bypass (CPB) time (p < 0.01), and ejection fraction (EF, p < 0.01) were the risk factors for POAF. Multivariate logistic regression analysis determined the independent risk factors associated with POAF were old age (odds ratio [OR] = 1.062, p = 0.000) and low EF (OR = 0.980; p = 0.008). CONCLUSIONS: In the current era, after isolated CABG surgery, there is still a quite high incidence of POAF (30.94% in this group of CABG patients). The main risk factors correlating to POAF include age, hypertension, smoking, CPB time, and EF. Among these factors, multivariate analysis identified old age and low EF as the independent risk factors associated with POAF. Particular care should be taken in the perioperative period for these patients in the prevention of POAF.

Ablative Treatments and Surgery for Early-Stage Hepatocellular Carcinoma: A Network Meta-Analysis.

BACKGROUND: We compared overall survival (OS) and disease-free survival (DFS) for hepatocellular carcinoma (HCC) following radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, and liver resection (LR), with the aim of evaluating treatment plans for early-stage HCC. METHODS: Studies in PubMed, Web of Science, and Cochrane databases from April 1, 2004, to April 1, 2024, were searched. Articles were evaluated for quality using the randomized controlled trials tool. Two tool and the Newcastle-Ottawa Scale. Data obtained from the literature were netted using Stata 15.0 and r 4.2.3. The assessed primary outcomes were OS and DFS at 1 and 3 y. RESULTS: A total of 25 publications with 4548 patients were included, including 13 studies in mainland China and 12 in other regions. For 1-y DFS, the hazard ratio (HR) was 0.54 (95% credible interval (CrI): 0.38-0.76) for LR compared with RFA and 0.57 (95% CrI: 0.3--0.82) for LR compared with MWA. For 3-y DFS, the HR was 0.52 (95% CrI: 0.38-0.72) for LR compared with RFA and 0.53 (95% CrI: 0.37-0.76). In the Chinese mainland, LR may have a better 1- and 3-y DFS than MWA, but similar survival to RFA. In the other regions, LR had a better DFS than MWA and RFA patients. The rest of the comparisons were not statistically significant. CONCLUSIONS: For early-stage HCC, LR may be more effective in reducing tumor recurrence than ablative treatments. Cryoablation may be a potential treatment for HCC. The differences in treatment effectiveness in different regions are worth further study.

Association between serum pyridoxal 5'-phosphate levels and all-cause, cardiovascular mortality, and cardiovascular disease in adults: a population-based cohort study.

Background: The association between pyridoxal 5'-phosphate (PLP) and cardiovascular disease (CVD) remains a topic of discussion. Objectives: This study aimed to explore the relationship between serum PLP levels and the incidence of all-cause mortality, cardiovascular mortality, and the risk of CVD among the US population. Design: A population-based cohort study. Methods: This study analyzed data from the National Health and Nutrition Examination Survey. Adjusted hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were calculated using weighted Cox proportional hazards regression models to assess the risk associated with all-cause and cardiovascular mortality. Weighted binary logistic regression was utilized to assess the relationship between serum PLP levels and the risk of CVD. Nonlinear associations were evaluated using multivariable-adjusted restricted cubic splines. Results: There were 2546 cases of all-cause mortality and 867 cases of cardiovascular mortality over a mean follow-up of 11.36 years. In the fully adjusted model, the adjusted HRs with 95% CIs for all-cause mortality associated with increases in serum PLP levels corresponding to the interquartile ranges were 0.83 (0.74-0.93), 0.71 (0.63-0.80), and 0.64 (0.56-0.74), respectively. Similarly, cardiovascular mortality decreased by 0.78 (0.62-0.97), 0.63 (0.49-0.81), and 0.62 (0.50-0.77) with each quartile increase in serum PLP levels. Higher serum PLP levels confer protection against CVD risk (odds ratio: 0.87, 95% CI: 0.79-0.96). Serum PLP levels showed nonlinear relationships with risk of all-cause mortality, cardiovascular mortality, and CVD. Conclusion: The results of this study provide evidence that serum PLP serves as a protective factor against all-cause mortality, cardiovascular mortality, and CVD in US adults, with dose-response relationships.

Association between serum pyridoxal 5'-phosphate levels and all-cause, cardiovascular mortality, and cardiovascular disease in US adults Why was the study done? The association between pyridoxal 5'-phosphate (PLP) and cardiovascular disease (CVD) remains a topic of discussion. This study aimed to explore the relationship between serum PLP levels and the incidence of all-cause mortality, cardiovascular mortality, and the risk of CVD among the US population. What did the researchers do? This study used data from National Health and Nutrition Examination Survey (NHANES), applying statistical methods to see if there's a connection between the amount of PLP in the blood and health outcomes. What did the researchers find? The findings showed that over an average of 11 years, people with higher levels of PLP in their blood were less likely to die for any reason. They were also less likely to die from heart-related problems or to develop heart disease. The protection seemed to increase as PLP levels got higher. What do the findings mean? The results of this study provide evidence that serum PLP serves as a protective factor against all-cause mortality, cardiovascular mortality, and cardiovascular disease in US adults, with dose­response relationships.

Persistent Mayer Dirac.

Topological data analysis (TDA) has made significant progress in developing a new class of fundamental operators known as the Dirac operator, particularly in topological signals and molecular representations. However, the current approaches being used are based on the classical case of chain complexes. The present study establishes Mayer Dirac operators based on N-chain complexes. These operators interconnect an alternating sequence of Mayer Laplacian operators, providing a generalization of the classical result D 2 = L . Furthermore, the research presents an explicit formulation of the Laplacian for N-chain complexes induced by vertex sequences on a finite set. Weighted versions of Mayer Laplacian and Dirac operators are introduced to expand the scope and improve applicability, showcasing their effectiveness in capturing physical attributes in various practical scenarios. The study presents a generalized version for factorizing Laplacian operators as an operator's product and its 'adjoint'. Additionally, the proposed persistent Mayer Dirac operators and extensions are applied to biological and chemical domains, particularly in the analysis of molecular structures. The study also highlights the potential applications of persistent Mayer Dirac operators in data science.

KIF15 promotes human glioblastoma progression under the synergistic transactivation of REST and P300.

Glioblastoma (GBM) is highly invasive and lethal. The failure to cure GBM highlights the necessity of developing more effective targeted therapeutic strategies. KIF15 is a motor protein to be involved in cell mitosis promotion, cell structure assembly and cell signal transduction. The precise biological function and the potential upstream regulatory mechanisms of KIF15 in GBM remain elusive. Here, we demonstrated that KIF15 was abnormally up-regulated in GBM and predicted poor prognosis of GBM patients. KIF15 promotes GBM cell proliferation, metastasis and cell cycle progression. REST could bind to KIF15 promoter and transactivate KIF15. Furthermore, REST interacts with P300 and depends on its histone acetyltransferase (HAT) activity to co-regulate KIF15 expression. Both REST and P300 were highly expressed in GBM and predicted poor prognosis of GBM patients alone or in combination with KIF15. The tumorigenic function of KIF15 in GBM was regulated by REST in vitro and in vivo and the combinational treatment of cell cycle inhibitor Palbociclib with P300 HAT inhibitor inhibited GBM xenografts survival more significantly. Our findings indicate that KIF15 promotes GBM progression under the synergistic transactivation of REST and P300. P300/REST/KIF15 signaling axis is expected to be served as a cascade of candidate therapeutic targets in anti-GBM.

IL-1 receptor-associated kinase 3 (IRAK3) in lung adenocarcinoma predicts prognosis and immunotherapy resistance: involvement of multiple inflammation-related pathways.

Background: Lung cancer is a globally prevailing malignancy, and the predominant histological subtype is lung adenocarcinoma (LUAD). IL-1 receptor-associated kinase 3 (IRAK3) has been identified in connection with innate immune and inflammatory response. The aim of this study is to investigate the impact of IRAK3 on prognosis and immunotherapy efficacy in LUAD, which remains incompletely elucidated. Methods: Our study delved into multiple online databases to find out expression, methylation and prognostic potentials of IRAK3 in LUAD and other malignancies. We employed tissue microarrays to assess IRAK3 protein levels in our LUAD cohort [National Cancer Center (NCC), China] and explore prognostic values. The correlations between IRAK3 and immune infiltration based on The Cancer Genome Atlas (TCGA) data were analyzed by corresponding algorithms. The contribution of IRAK3 to immunotherapy response was explored through the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. Both LinkedOmics database and gene set enrichment analysis (GSEA) were applied to investigate how IRAK3 influences the tumor immune microenvironment and regulates immunotherapy response. We applied single-cell RNA sequencing datasets for the investigation of IRAK3 expression across diverse immune cells. Moreover, we employed genomics of drug sensitivity in cancer (GDSC) databases to examine how IRKA3 expression correlates with different drug responses. Results: Compared with normal tissues, various tumor tissues had lower IRAK3 expression which could be regulated by its high methylation level. Reduced IRAK3 protein level was observed to correlate with advanced tumor stages and unfavorable prognosis among patients with LUAD, especially individuals with lymph node metastasis. Gene set enrichment analysis (GSEA) and tumor infiltration analysis proved that IRAK3 provoked immune infiltration. Macrophages/monocytes, CD4+ T cells, CD8+ T cells and neutrophils correlated significantly with IRAK3 expression. With TIDE algorithm, IRAK3 was verified to be related to poor immune checkpoint blockade (ICB) response. IRAK3 demonstrated positive associations with T-cell dysfunction score and immune checkpoint markers. Conversely, it exhibited negative correlations with microsatellite instability (MSI) and tumor mutation burden (TMB). High IRAK3 expression exacerbated cytotoxic T lymphocyte (CTL) dysfunction and predicted immunotherapy resistance by involvement of multiple inflammation-related pathways including IL-6/JAK/STAT3 signaling, inflammatory response and interferon-gamma (IFN-γ) response pathways. Additionally, elevated IRAK3 expression was predicted to be related with better responses to chemotherapeutic and molecular targeted drugs. Conclusions: Our findings indicated that IRAK3 could function as an independent prognostic predictor and an immunotherapeutic indicator in LUAD through involvement of multiple inflammation-related pathways.

Advancements in enzymatic reaction-mediated microbial transformation.

Enzymatic reaction-mediated microbial transformation has emerged as a promising technology with significant potential in various industries. These technologies offer the ability to produce enzymes on a large scale, optimize their functionality, and enable sustainable production processes. By utilizing microbial hosts and manipulating their genetic makeup, enzymes can be synthesized efficiently and tailored to meet specific industrial requirements. This leads to enhanced enzyme performance and selectivity, facilitating the development of novel processes and the production of valuable compounds. Moreover, microbial transformation and biosynthesis offer sustainable alternatives to traditional chemical methods, reducing environmental impact and promoting greener production practices. Microbial transformations enrich drug candidate diversity and enhance active ingredient potency, benefiting the pharmaceutical industry. Continued advancements in genetic engineering and bioprocess optimization drive further innovation and application development in Enzymatic reaction-mediated microbial transformation. The integration of AI for predicting enzymatic reactions and optimizing pathways marks a promising direction for future research. In summary, these technologies have the potential to revolutionize several industries by providing cost-effective, sustainable solutions.

RAB18 regulates extrahepatic siRNA-mediated gene silencing efficacy.

Small interfering RNAs (siRNAs) hold considerable therapeutic potential to selectively silence previously "undruggable" disease-associated targets, offering new opportunities to fight human diseases. This therapeutic strategy, however, is limited by the inability of naked siRNAs to passively diffuse across cellular membranes due to their large molecular size and negative charge. Delivery of siRNAs to liver through conjugation of siRNA to N-acetylgalactosamine (GalNAc) has been a success, providing robust and durable gene knockdown, specifically in hepatocytes. However, the poor delivery and silencing efficacy of siRNAs in other cell types has hindered their applications outside the liver. We previously reported that a genome-wide pooled knockout screen identified RAB18 as a major modulator of GalNAc-siRNA conjugates. Herein, we demonstrate RAB18 knockout/knockdown efficaciously enhances siRNA-mediated gene silencing in hepatic and extrahepatic cell lines and in vivo. Our results reveal a mechanism by which retrograde Golgi-endoplasmic reticulum (ER) transport and the intracellular lipid droplets (LDs) positively regulate siRNA-mediated gene silencing.

Cross-attention mechanism-based spectrum sensing in generalized Gaussian noise.

Spectrum sensing (SS) technology is essential for cognitive radio (CR) networks to effectively identify and utilize idle spectrum resources. Due to the influence of noise characteristics in the channel, providing accurate sensing results is challenging. In order to improve the performance of SS under non-Gaussian noise and overcome the limitations of existing methods that are mostly based on a single feature, we propose a novel time-frequency cross fusion network (TFCFN). Specifically, we utilize gated recurrent units (GRU) to capture long-term dependencies in the time domain on the original signals, meanwhile, we perform a fast Fourier transform (FFT) on the original signals to obtain the frequency domain information, and subsequently use convolutional neural networks (CNN) to extract the local spatial features in the frequency domain. Ultimately, these time-domain and frequency-domain features are dynamically fused through a cross-attention mechanism to construct more comprehensive and robust features for signal classification. We use generalized Gaussian distribution (GGD) as the noise model and reconstruct the RadioML2016.10a dataset to explore the performance under various noise conditions. The experimental results show that compared with the baseline methods, TFCFN exhibits better detection ability and maintains lower complexity in both Gaussian and non-Gaussian noise environments. Notably, when the shape parameter of GGD is set to 0.5 and the signal-to-noise ratio (SNR) of the received signal is -16dB, it can maintain the probability of false alarm ( P f ) of 10% while still ensuring the probability of detection ( P d ) of over 90%.

RNA surveillance by the RNA helicase MTR4 determines volume of mouse oocytes.

Oocytes are the largest cell type in multicellular animals. Here, we show that mRNA transporter 4 (MTR4) is indispensable for oocyte growth and functions as part of the RNA surveillance mechanism, which is responsible for nuclear waste RNA clearance. MTR4 ensures the normal post-transcriptional processing of maternal RNAs, their nuclear export to the cytoplasm, and the accumulation of properly processed transcripts. Oocytes with Mtr4 knockout fail to accumulate sufficient and normal transcripts in the cytoplasm and cannot grow to normal sizes. MTR4-dependent RNA surveillance has a previously unrecognized function in maintaining a stable nuclear environment for the establishment of non-canonical histone H3 lysine-4 trimethylation and chromatin reorganization, which is necessary to form a nucleolus-like structure in oocytes. In conclusion, MTR4-dependent RNA surveillance activity is a checkpoint that allows oocytes to grow to a normal size, undergo nuclear and cytoplasmic maturation, and acquire developmental competence.

Corrigendum: Risk of SARS-CoV-2 infection among people living with HIV in Wuhan, China.

[This corrects the article DOI: 10.3389/fpubh.2022.833783.].

Chiral Co-assembly Based on a Stimuli-Responsive Polymer towards Amplified Full-Color Circularly Polarized Luminescence.

Stimuli-responsive circularly polarized luminescence (CPL) materials have been attaching wide attention in the field of optical information storage and encryption, while still facing the challenge of the realization of high luminescence dissymmetry factors (glum). This work presents a pair of stimuli-responsive chiral co-assemblies P7R3 and P7S3 by combining polymer PFIQ containing iso-quinoline units with chiral inducers. The obtained chiral co-assemblies can reversibly undergo significant modification in CPL behavior under trifluoroacetic acid (TFA) fumigation and annealing treatment, with the |glum| values exhibiting a reversible shift between 0.2 and 0.3. Moreover, the chiral co-assemblies before TFA fumigating can effectively induce achiral emitters to generate intense full-color CPL signals through CPL energy transfer (CPL-ET), with the corresponding |glum| values larger than 0.2. Moreover, information encryption and decryption as well as a multi-level logic gates application are achieved by leveraging the reversible stimuli-responsive CPL activity of the chiral co-assembly. This work provides a new perspective for the construction of stimuli-responsive chiral luminescent materials with large |glum| values and the activation of CPL behavior in achiral emitters.

CHATGPT FOR COMPUTATIONAL TOPOLOGY.

ChatGPT represents a significant milestone in the field of artificial intelligence (AI), finding widespread applications across diverse domains. However, its effectiveness in mathematical contexts has been somewhat constrained by its susceptibility to conceptual errors. Concurrently, topological data analysis (TDA), a relatively new discipline, has garnered substantial interest in recent years. Nonetheless, the advancement of TDA is impeded by the limited understanding of computational algorithms and coding proficiency among theoreticians. This work endeavors to bridge the gap between theoretical topological concepts and their practical implementation in computational topology through the utilization of ChatGPT. We showcase how a pure theoretician, devoid of computational experience and coding skills, can effectively transform mathematical formulations and concepts into functional codes for computational topology with the assistance of ChatGPT. Our strategy outlines a productive process wherein a mathematician trains ChatGPT on pure mathematical concepts, steers ChatGPT towards generating computational topology codes, and subsequently validates the generated codes using established examples. Our specific case studies encompass the computation of Betti numbers, Laplacian matrices, and Dirac matrices for simplicial complexes, as well as the persistence of various homologies and Laplacians. Furthermore, we explore the application of ChatGPT in computing recently developed topological theories for hypergraphs and digraphs, as well as the persistent harmonic space, which has not been computed in the literature, to the best of our knowledge. This work serves as an initial step towards effectively transforming pure mathematical theories into practical computational tools, with the ultimate goal of enabling real applications across diverse fields.

CEACAM1 increased the lymphangiogenesis through miR-423-5p and NF- kB in Non-Small Cell Lung Cancer.

Background: Lung cancer causes significant mortality, with invasion and metastasis being the main features that cause most cancer deaths. Lymph node metastasis is the primary metastatic route in non-small cell carcinoma (NSCLC) and influences the staging and prognosis of NSCLC. Cumulative studies have reported that Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is involved in the progression of various cancers. However, few studies have discussed the function of CEACAM1 in lymphangiogenesis in NSCLC. Here, we examined how CEACAM1 influences lymphangiogenesis in NSCLC. Methods: A total of 30 primary squamous cell carcinoma (LUSC) patients diagnosed with LN metastasis were prospectively selected. LUSC tumor tissues, para-cancerous tissues, and positive lymph node tissues were harvested. The expression and subcellular location of CEACAM1, CD31, and LVYE1 in clinical samples were detected by immunohistochemistry. Next, the CEACAM1 and hsa-miR-423-5p expressions were detected by qPCR. The protein expression of lymphangiogenesis-associated proteins and critical cytokines of the NF-κB pathway in HDLECs was detected by Western blot. A tube formation assay was performed to detect the lymphangiogenesis in different groups. The interaction between CEACAM1 and hsa-miR-423-5p was verified using a dual luciferase assay. Results: CEACAM1 was found to be a potential gene associated with lung cancer prognosis. It was positively correlated with angiogenesis and lymphangiogenesis. Then, we detected the function of CEACAM1 in lymphangiogenesis and found that CEACAM1 promoted lymphangiogenesis. hsa-miR-423-5p overexpression inhibited lymphangiogenesis via targeting CEACAM1. Finally, we observed that CEACAM1 can activate the NF-κB pathway and, therefore, promote lymphangiogenesis. Conclusion: We found that CEACAM1 enhanced lymphangiogenesis in NSCLC via NF-kB activation and was repressed by miR-423-5p. This suggests the value of CEACAM1 as a new therapeutic marker in NSCLC.

Prospects and challenges of neoantigen applications in oncology.

Neoantigen, unique peptides resulting from tumor-specific mutations, represent a promising frontier in oncology for personalized cancer immunotherapy. Their unique features allow for the development of highly specific and effective cancer treatments, which can potentially overcome the limitations of conventional therapies. This paper explores the current prospects and challenges associated with the application of neoantigens in oncology. We examine the latest advances in neoantigen identification, vaccine development, and adoptive T cell therapy. Additionally, we discuss the obstacles related to neoantigen heterogeneity, immunogenicity prediction, and the tumor microenvironment. Through a comprehensive analysis of current research and clinical trials, this paper aims to provide a detailed overview of how neoantigens could revolutionize cancer treatment and the hurdles that must be overcome to realize their full potential.

Boosting the Strength and Toughness of Polymer Blends via Ligand-Modulated MOFs.

Mechanically robust and tough polymeric materials are in high demand for applications ranging from flexible electronics to aerospace. However, achieving both high toughness and strength in polymers remains a significant challenge due to their inherently contradictory nature. Here, a universal strategy for enhancing the toughness and strength of polymer blends using ligand-modulated metal-organic framework (MOF) nanoparticles is presented, which are engineered to have adjustable hydrophilicity and lipophilicity by varying the types and ratios of ligands. Molecular dynamics (MD) simulations demonstrate that these nanoparticles can effectively regulate the interfaces between chemically distinct polymers based on their amphiphilicity. Remarkably, a mere 0.1 wt.% of MOF nanoparticles with optimized amphiphilicity (ML-MOF(5:5)) delivered ≈3.4- and ≈34.1-fold increase in strength and toughness of poly (lactic acid) (PLA)/poly (butylene succinate) (PBS) blend, respectively. Moreover, these amphiphilicity-tailorable MOF nanoparticles universally enhance the mechanical properties of various polymer blends, such as polypropylene (PP)/polyethylene (PE), PP/polystyrene (PS), PLA/poly (butylene adipate-co-terephthalate) (PBAT), and PLA/polycaprolactone (PCL)/PBS. This simple universal method offers significant potential for strengthening and toughening various polymer blends.

The association between thyroid disease and hearing loss: a meta-analysis.

BACKGROUND: It has been shown that there is a link between thyroid-related diseases and hearing loss. OBJECTIVES: The purpose of this study is to investigate the relationship between thyroid-related diseases and hearing loss by conducting a meta-analysis. MATERIAL AND METHODS: A thorough search was carried out in the following electronic databases: PubMed, Cochrane Library, Embase, Web of Science, Google Scholar, Semantic Scholar, and ResearchRabbit. The chi-square test and the I2 index examined the research's heterogeneity. A funnel plot and the Eger test were used to examine publication-biased effects. RESULTS: A total of 48,507 individuals (6482 hypothyroid patients, 4162 hearing loss patients, and 37863 controls) were included in this meta-analysis of 18 research. Individuals with hypothyroidism had a 1.69-fold increased risk of hearing loss compared to those without the condition (OR: 1.69; 95% CI: 1.11-2.57, p < 0.001). among hypothyroidism, the prevalence of hearing loss was 24% (EC: 0.24; 95% CI: 0.11-0.39, p = 0.00), while among hearing-impaired individuals, the prevalence of hypothyroidism was 7% (EC: 0.21; 95% CI: 0.07-0.40). CONCLUSION: This study demonstrated how thyroid dysfunction can raise the chance of hearing loss. To completely comprehend the underlying mechanisms and create efficient treatments for this illness, more study is required.

Long-term transcranial ultrasound stimulation regulates neuroinflammation to ameliorate post-myocardial infarction cardiac arrhythmia and remodeling.

BACKGROUND: Sympathetic overactivation and neuroinflammation in the paraventricular nucleus (PVN) are crucial factors in post-myocardial infarction (MI) cardiac remodeling and ventricular arrhythmias (VAs). Prior study has indicated that low-intensity focused ultrasound stimulation could attenuate sympathetic neuroinflammation within the PVN to prevent the occurrence of VAs in acute MI model. Meanwhile, the cGAS-STING pathway has shown potential to ameliorate neuroinflammatory response. However, the effect and mechanisms of long-term transcranial ultrasound stimulation (LTUS) for modulating neuroinflammation in the chronic stage of MI remain unclear. OBJECTIVE: The current study aims to ascertain whether LTUS could mitigate post-MI neuroinflammation and improve cardiac arrhythmia and remodeling through the cGAS-STING pathway. METHODS: Thirty-six SD rats were equally randomized to the Sham group (pseudo-MI modeling), CMI group (MI modeling), and LTUS group (MI modeling and long-term ultrasound stimulation). Transcranial ultrasound stimulation (15 min/day) was conducted on the PVN for 4 consecutive weeks. After 4-week intervention, the echocardiography, electrophysiological experiment and histopathological staining were performed to assess the role of LTUS on post-MI neuroinflammation and cardiac remodeling. RESULTS: The results indicated that LTUS significantly facilitated microglial M1-to-M2 polarization via cGAS-STING signaling pathway within the PVN. Furthermore, LTUS inhibited MI-induced sympathetic neuroinflammation, thereby improving cardiac dysfunction, ameliorating cardiac remodeling, and reducing VA inducibility. CONCLUSION: Long-term ultrasound stimulation of the PVN was found to alleviate post-MI neuroinflammation and improve cardiac remodeling, which might inspire novel insights and clinical strategies for non-invasive neuromodulation and the treatment of post-MI VAs.