Aspirin is associated with improved outcomes in patients with sepsis-induced myocardial injury: An analysis of the MIMIC-IV database.

BACKGROUND: The effectiveness of aspirin treatment in septic patients remains a subject of debates. OBJECTIVE: To explore the association between aspirin usage and the prognosis of patients with sepsis-induced myocardial injury (SIMI), as well as the timing of aspirin administration. METHODS: Patients with SIMI were screened in the MIMIC-IV database and categorized into aspirin and non-aspirin groups based on their medications during intensive care unit (ICU) stay, and propensity matching analysis (PSM) was subsequently performed to reduce bias at baseline between the groups. The primary outcome was 28-day all-cause mortality. Cox multivariate regression analysis was conducted to evaluate the impact of aspirin on the prognosis of patients with SIMI. RESULTS: The pre-PSM and post-PSM cohorts included 1170 and 1055 patients, respectively. In the pre-PSM cohort, the aspirin group is older, has a higher proportion of chronic comorbidities, and lower SOFA and SAPS II scores when compared to the non-aspirin group. In the PSM analysis, most of the baseline characterization biases were corrected, and aspirin use was also associated with lower 28-day mortality (hazard ratio [HR] = 0.51, 95 % confidence interval [CI]: 0.42-0.63, P < 0.001), 90-day mortality (HR = 0.58, 95 % CI: 0.49-0.69, P < 0.001) and 1-year mortality (HR = 0.65, 95 % CI: 0.56-0.76, P < 0.001), irrespective of aspirin administration timing. A sensitivity analysis based on the original cohort confirmed the robustness of the findings. Additionally, subsequent subgroup analysis revealed that the use of vasopressin have a significant interaction with aspirin's efficacy. CONCLUSION: Aspirin was associated with decreased mortality in SIMI patients, and this beneficial effect persisted regardless of pre-ICU treatment.

Paper-based colorimetric sensor using a single-atom nanozyme for the ultrasensitive detection of Cr(VI) in short-necked clams.

Single-atom nanozymes (SAzymes) as a class of highly active nanozymes with the advantages of high atom utilization, high catalytic activity and stability have attracted great attention. In this work, Fe-N-C SAzymes with exceptional oxidase (OXD)-like activity were achieved utilizing polyvinylpyrrolidone (PVP) as a template. The Fe-N-C SAzymes with remarkable OXD-like activity could oxidize TMB to blue oxTMB, but 8-hydroxyquinoline (8-HQ) as a metal chelator is capable of discoloring oxTMB. Thus, the addition of 8-HQ decolorized the solution. However, upon the introduction of Cr(VI) ions, 8-HQ preferentially chelated with the Cr(VI) ions, reversing the inhibition of the color reaction and restoring the blue color. Based on this phenomenon, we constructed a novel paper-based analytical device (PAD) that exhibited a linear range of 5-1000 µM and an LOD of 1.2 µM. Importantly, the PAD used in this study shows the merits of simplicity, low preparation costs, and rapid reaction times. When combined with smartphone RGB analysis, it enables the simultaneous analysis of eight different Cr(VI) concentrations without the need for large-scale instrumentation. Moreover, the proposed PAD displays high selectivity, accuracy and utility in testing actual short-necked clam samples. This work not only provides a simple and cost-effective method to detect Cr(VI) but also makes a contribution to rapid food testing.

Tonsillectomy Versus Tonsillotomy in Pediatric Sleep-Disordered Breathing: A Systematic Review and Multi-subgroup Meta-analysis.

OBJECTIVES: To evaluate the potential of tonsillotomy (TT) as an alternative to tonsillectomy (TE) for treating children with obstructive sleep-disordered breathing (oSDB). DATA SOURCES: Two independent reviewers searched PubMed, the Cochrane Library, Embase, and additional sources to identify controlled studies comparing TT versus TE in pediatric patients with oSDB. REVIEW METHODS: We evaluated post-surgery symptom relief, and short- and long-term postoperative benefits for children. Fixed-effect meta-analysis, sensitivity analysis, and subgroup analysis were conducted. RESULTS: In our analysis of 32 studies with 9,430 children, the analysis revealed TT group had a similar therapeutic effect on improvement of OSA-18 as TE group (MD = 5.20, 95% CI: -32.67 to 43.07, p = 0.96). In terms of short-term outcome, the days to return to normal diet for TT group were shorter than that for TE group (MD = -2.49, 95%CI: -3.57 to -1.28; p < 0.001), less analgesics use (MD = -3.19, 95% CI = -3.44 to -2.93, p < 0.001), and lower postoperative secondary bleeding (RR = 0.33; 95%CI: 0.23 to 0.47; p < 0.001). But the risk of reoperation (OR = 8.28; 95%CI: 2.66 to 12.64; p < 0.001), oSDB recurrence (OR = 2.16; 95%CI: 1.20-3.86; p = 0.01), and postoperative infection (OR = 1.82; 95%CI: 1.34 to 2.47; p < 0.001) in TT group was significantly higher than that in TE group. CONCLUSIONS: Tonsillotomy reduces postoperative pain and bleeding, speeding up recovery for children with oSDB, and improving their quality of life. Yet, the risk of recurrent infections from residual tonsil tissue, which may require reoperation, calls for a careful evaluation of the procedure's short-term gains against its long-term risks. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Smartphone-assisted colorimetric sensor arrays based on nanozymes for high throughput identification of heavy metal ions in salmon.

The rapid, precise, and high-throughput identification of multiple heavy metals ions holds immense importance in ensuring food safety and promoting public health. This study presents a novel smartphone-assisted colorimetric sensor array for the rapid and precise detection of multiple heavy metals ions. The sensor array is based on three signal recognition elements (AuPt@Fe-N-C, AuPt@N-C, and Fe-N-C) and the presence of different heavy metal ions affects the nanozymes-chromogenic substrate (TMB) catalytic color production, enabling the differentiation and quantification of various heavy metal ions. Combined with a smartphone-based RGB mode, the colorimetric sensor array can successfully identify five different heavy metal ions (Hg2+, Pb2+, Co2+, Cr6+, and Fe3+) as low as 0.5 µM and different ratios of binary and ternary mixed heavy metal ions in just 5 min. The sensor array successfully tested seawater and salmon samples with a total heavy metal content of 10 µM in the South China Sea (Haikou and Wenchang). Overall, this study highlights the potential of smartphone-assisted colorimetric sensor arrays for the rapid and precise detection of multiple heavy metal ions, which could significantly contribute to food safety and public health monitoring.

UBE3C restricts EV-A71 replication by ubiquitination-dependent degradation of 2C.

Ubiquitin modification of viral proteins to degrade or regulate their function is one of the strategies of the host to resist viral infection. Here, we report that ubiquitin protein ligase E3C (UBE3C), an E3 ubiquitin ligase, displayed inhibitory effects on EV-A71 replication. UBE3C knockdown resulted in increased viral protein levels and virus titers, whereas overexpression of UBE3C reduced EV-A71 replication. To explore the mechanism by which UBE3C affected EV-A71 infection, we found that the C-terminal of UBE3C bound to 2C protein and facilitated K33/K48-linked ubiquitination degradation of 2C K268. Moreover, UBE3C lost its ability to degrade 2C K268R and had a diminished inhibitory impact against the replication of recombinant EV-A71-FY-2C K268R. In addition, UBE3C also promoted ubiquitination degradation of the 2C protein of CVB3 and CVA16 and inhibited viral replication. Thus, our findings reveal a novel mechanism that UBE3C acts as an enterovirus host restriction factor, including EV-A71, by targeting the 2C protein. IMPORTANCE: The highly conserved 2C protein of EV-A71 is a multifunctional protein and plays a key role in the replication cycle. In this study, we demonstrated for the first time that UBE3C promoted the degradation of 2C K268 via K33/K48-linked ubiquitination, thereby inhibiting viral proliferation. Our findings advance the knowledge related to the roles of 2C in EV-A71 virulence and the ubiquitination pathway in the host restriction of EV-A71 infection.

Prediction models of intravenous glucocorticoids therapy response in thyroid eye disease.

Background: Thyroid eye disease (TED) is an autoimmune orbital disease, with intravenous glucocorticoid (IVGC) therapy as the first-line treatment. Due to uncertain response rates and possible side effects, various prediction models have been developed to predict IVGC therapy outcomes. Methods: A thorough search was conducted in PubMed, Embase, and Web of Science databases. Data extraction included publication details, prediction model content, and performance. Statistical analysis was performed using R software, including heterogeneity evaluation, publication bias, subgroup analysis, and sensitivity analysis. Forest plots were utilized for result visualization. Results: Of the 12 eligible studies, 47 prediction models were extracted. All included studies exhibited a low-to-moderate risk of bias. The pooled area under the receiver operating characteristic curve (AUC) and the combined sensitivity and specificity for the models were 0.81, 0.75, and 0.79, respectively. In view of heterogeneity, multiple meta-regression and subgroup analysis were conducted, which showed that marker and modeling types may be the possible causes of heterogeneity (P < 0.001). Notably, imaging metrics alone (AUC = 0.81) or clinical characteristics combined with other markers (AUC = 0.87), incorporating with multivariate regression (AUC = 0.84) or radiomics analysis (AUC = 0.91), yielded robust and reliable prediction outcomes. Conclusion: This meta-analysis comprehensively reviews the predictive models for IVGC therapy response in TED. It underscores that integrating clinical characteristics with laboratory or imaging indicators and employing advanced techniques like multivariate regression or radiomics analysis significantly enhance the efficacy of prediction. Our research findings offer valuable insights that can guide future studies on prediction models for IVGC therapy in TED.

Clinical evolution of bladder carcinosarcoma: A case report and literature review.

RATIONALE: Bladder carcinosarcoma (BC) is a malignant tumor composed of a mixture of malignant epithelial and stromal components. Carcinosarcoma mostly occurs in the upper respiratory tract and upper gastrointestinal tract and is less common in the urinary system. The incidence of malignant tumors of the urinary system is <3%. It rarely occurs in the bladder and accounts for approximately 0.31% of all malignant bladder tumors. A literature review and this report will help to further improve our understanding, diagnosis, and treatment of bladder carcinosarcoma (BC). PATIENT CONCERN: We describe the case of an 80-year-old female patient who was admitted to the hospital with a history of intermittent hematuria for 3 years. Furthermore, total cystectomy was refused when a BC was diagnosed. Palliative resection surgery was necessary because of the recurrent hematuria and abdominal pain. DIAGNOSES: Pathologically confirmed BC after surgery. INTERVENTIONS: The patient's first transurethral resection of bladder tumor (TURBT) was diagnosed as BC. However, the patient refused a total cystectomy. Two months after intravesical treatment with epirubicin, bladder tumor recurrence was observed during follow-up cystoscopy. The patient underwent a second TURBT for hemostatic treatment due to persistent hematuria. Due to hematuria and abdominal pain, a third TURBT was performed to reduce tumor size and stop bleeding. Finally, tumor recurrence resulted in bilateral hydronephrosis, and the patient underwent bilateral renal catheter drainage guided by B-ultrasound. OUTCOMES: Bladder carcinosarcoma caused uremia, electrolyte imbalance, and sepsis. Approximately 19 months after the discovery of the tumor, the patient died. LESSONS: Radical bladder resection is recommended once a BC is diagnosed. By reporting the cases and reviewing the literature in the database, we will summarize the epidemiology, origin, etiology, clinical features, existing treatments, and prognostic factors of BC, and propose new prospects for BC therapy.

Evaluating the therapeutic effect of LIPUS in the early stage of traumatic brain injury using FA and T2* in rats.

To evaluate the protective effect of LIPUS at the early stage of brain trauma in rats, 45 rats were randomly divided into 3 groups: sham (n = 15), TBI (n = 15) and LIPUS treatment groups (n = 15). Ipsilateral and contralateral cortical and thalamic parameters obtained by diffusion tensor imaging (DTI) and fast low-angle shot magnetic resonance imaging (FLASH-MRI) were measured at different times after trauma. For fractional anisotropy (FA) and T2* values, two-way repeated measures ANOVA with Tukey's post hoc was used for intergroup comparisons. With observation time prolonged, the FA values of the ipsilateral cortex in the TBI group gradually increased and were significantly higher than those in the LIPUS treatment group on Day 7 (adjusted P = 0.0067). FA values in the contralateral cortex decreased at this time and were significantly lower than those in the LIPUS treatment group (adjusted P = 0.0192). Meanwhile, compared with LIPUS group, FA values were significantly higher in the injured thalamus (adjusted P = 0.0025). Combined with correlation analysis, FA values were positively correlated with neuronal damage (P = 0.0148, r2 = 0.895). At 7 days after trauma, T2* values in the ipsilateral cortex of the TBI group were significantly lower. After analysis of ferritin content and correlation, we found that T2* values were negatively correlated with ferritin (P = 0.0259, r2 = -0.849). By measuring post-traumatic changes in FA and T2* values, it is possible to demonstrate a neuronal protective effect of LIPUS in the early phase of TBI rats and promote brain rehabilitation.

Theoretical study on the insertion reaction of the stannylenoid H2SnLiF with X-H bonds (X = N, O, F).

The insertion reactions of p-complex (RP) and three-membered ring configuration (RS) of stannylenoid H2SnLiF with NH3, H2O and HF have been studied theoretically by quantum chemical calculation. The structures of reactants, precursors, transition states, intermediates and products have been fully optimized at the M06-2X/def2-TZVP level. The single point energy of all fixed points were calculated using the QCISD method. The calculation results show that the three-membered ring configuration is easier to conduct the insertion reaction. Comparing the reaction energy barriers of RP, RS to NH3, H2O and HF, we found that the difficulty of the insertion reaction is NH3 > H2O > HF. The solvent corrected calculation results show that in THF, the reaction energy barrier of RP is lower than that in vacuum, while the reaction energy barrier of RS is higher. This work provides theoretical support for the reaction properties of stannylenoid.

Comparison of immediate vs. delayed guided tissue regeneration in Infrabony defect of second molars after adjacent third molar extraction: a retrospective study.

BACKGROUND: The distal aspect of the second molar (d-M2) often exhibits infrabony defects due to the adjacent third molar. Although the defects can be treated by guided tissue regeneration (GTR) after removing the third molar, the optimal timing remains uncertain following third molar removal in clinical decision-making. This study aimed to compare delayed and immediate GTR treatments to assist in clinical decision-making. METHODS: D-M2 infrabony defects with a minimum 1-year follow-up were collected and divided into three groups: Immediate GTR group, which underwent third molar extraction and received GTR simultaneously; Delayed GTR group, which underwent delayed GTR at least 3 months after third molar extraction; and Control group, which underwent only scaling and root planing during third molar extraction. The clinical and radiographic parameters related to the infrabony defect before GTR and post-surgery were evaluated using the Kruskal-Wallis test or one-way ANOVA, followed by post-hoc Dunn's test or the Bonferroni test for pairwise comparisons. RESULTS: A total of 109 d-M2 infrabony defects were assessed. No significant differences were found between the two GTR groups, although both of them showed significant reductions in infrabony defect depth: the immediate GTR group (2.77 ± 1.97 mm vs. 0.68 ± 1.03 mm, p < 0.001) and the delayed GTR group (2.98 ± 1.08 mm vs. 0.68 ± 1.03 mm, p < 0.001) compared to the control group. CONCLUSION: GTR can effectively improve d-M2 infrabony defects when the third molar is removed, whether simultaneously or delayed. Patients may experience less discomfort with immediate GTR treatment as it requires only one surgery.

Plasma metabolomics reveals the shared and distinct metabolic disturbances associated with cardiovascular events in coronary artery disease.

Risk prediction for subsequent cardiovascular events remains an unmet clinical issue in patients with coronary artery disease. We aimed to investigate prognostic metabolic biomarkers by considering both shared and distinct metabolic disturbance associated with the composite and individual cardiovascular events. Here, we conducted an untargeted metabolomics analysis for 333 incident cardiovascular events and 333 matched controls. The cardiovascular events were designated as cardiovascular death, myocardial infarction/stroke and heart failure. A total of 23 shared differential metabolites were associated with the composite of cardiovascular events. The majority were middle and long chain acylcarnitines. Distinct metabolic patterns for individual events were revealed, and glycerophospholipids alteration was specific to heart failure. Notably, the addition of metabolites to clinical markers significantly improved heart failure risk prediction. This study highlights the potential significance of plasma metabolites on tailed risk assessment of cardiovascular events, and strengthens the understanding of the heterogenic mechanisms across different events.

Non-immune functions of B7-H3: bridging tumor cells and the tumor vasculature.

B7-H3 (CD276), an immune checkpoint molecule, is overexpressed in various types of cancer and their tumor vasculature, demonstrating significant associations with adverse clinical outcomes. In addition to its well-known immune functions, B7-H3 exhibits dual co-stimulatory/co-inhibitory roles in normal physiology and the tumor microenvironment. The non-immune functions of B7-H3 in tumor cells and the tumor vasculature, including promoting tumor cell anti-apoptosis, proliferation, invasion, migration, drug resistance, radioresistance, as well as affecting cellular metabolism and angiogenesis, have increasingly gained attention from researchers. Particularly, the co-expression of B7-H3 in both tumor cells and tumor endothelial cells highlights the higher potential and clinical utility of therapeutic strategies targeting B7-H3. This review aims to summarize the recent advances in understanding the non-immune functions of B7-H3 in tumors and provide insights into therapeutic approaches targeting B7-H3, focusing on its co-expression in tumor cells and endothelial cells. The aim is to establish a theoretical foundation and practical reference for the development and optimization of B7-H3-targeted therapies.

ATG10S promotes IFNL1 expression and autophagic degradation of multiple viral proteins mediated by IFNL1.

ATG10S is a newly discovered subtype of the autophagy protein ATG10. It promotes complete macroautophagy/autophagy, degrades multiple viral proteins, and increases the expression of type III interferons. Here, we aimed to investigate the mechanism of ATG10S cooperation with IFNL1 to degrade viral proteins from different viruses. Using western blot, immunoprecipitation (IP), tandem sensor RFP-GFP-LC3B and in situ proximity ligation assays, we showed that exogenous recombinant ATG10S protein (rHsATG10S) could enter into cells through clathrin, and ATG10S combined with ATG7 with IFNL1 assistance to facilitate ATG12-ATG5 conjugation, thereby contributing to the autophagosome formation in multiple cell lines containing different virions or viral proteins. The results of DNA IP and luciferase assays also showed that ATG10S was able to directly bind to a core motif (CAAGGG) within a binding site of transcription factor ZNF460 on the IFNL1 promoter, by which IFNL1 transcription was activated. These results clarified that ATG10S promoted autophagosome formation with the assistance of IFNL1 to ensure autophagy flux and autophagic degradation of multiple viral proteins and that ATG10S could also act as a novel transcription factor to promote IFNL1 gene expression. Importantly, this study further explored the antiviral mechanism of ATG10S interaction with type III interferon and provided a theoretical basis for the development of ATG10S into a new broad-spectrum antiviral protein drug.Abbreviation: ATG: autophagy related; ATG10S: the shorter isoform of autophagy-related 10; CC50: half cytotoxicity concentration; CCV: clathrin-coated transport vesicle; CLTC: clathrin heavy chain; CM: core motif; co-IP: co-immunoprecipitation; CPZ: chlorpromazine; ER: endoplasmic reticulum; HCV: hepatitis C virus; HBV: hepatitis B virus; HsCoV-OC43: Human coronavirus OC43; IFN: interferon; PLA: proximity ligation assay; rHsATG10S: recombinant human ATG10S protein; RLU: relative light unit; SQSTM1: sequestosome 1; ZNF: zinc finger protein.

Photochemical Synthesis of Thioesters from Aryl Halides and Carboxylic Acids.

Thioesters are important in synthesis, materials science, and biology, and their preparation traditionally relies on the use of disagreeable thiols. Here, we report a thiol-free protocol that stitches together widespread carboxylic acids and aryl halides, producing a diverse array of thioesters. Crucial to this strategy is the discovery that tetramethylthiourea can serve as both a sulfur source and, upon direct excitation by purple light, as a strong reductant, suitable for activating aryl halides via single-electron transfer. Coupling of the resulting aryl radicals provides an isothiouronium ion intermediate, which can be attacked by carboxylic acids via a polar pathway, affording the thioester products under mild conditions.

Elevated hepatitis B virus RNA levels in HBeAg-positive patients with low-level viraemia or previous low-level viraemia.

The understanding of viral transcription and replication activity in HBeAg-positive chronic hepatitis B (CHB) patients with low-level viraemia (LLV) or previous low-level viraemia (pre-LLV) remains unclear. Our aim was to evaluate and compare circulating hepatitis B virus (HBV) RNA levels in these patient groups with those achieving maintained virological response (MVR). This cross-sectional study included 147 patients: 43 in the LLV group, 25 in the pre-LLV group and 79 in the MVR group. Serum HBV RNA levels were assessed using specific RNA target capture combined with simultaneous amplification and testing method. Propensity score matching (PSM) was used to balance baseline characteristics between groups. Median HBV RNA levels were 6.9 copies/mL in the LLV group, 6.1 copies/mL in the pre-LLV group and 3.8 copies/mL in the MVR group. After PSM, significantly higher HBV RNA levels were observed in the LLV group compared to the MVR group (p < .001), and the pre-LLV group also showed higher HBV RNA levels than the MVR group (p < .001). Both LLV and pre-LLV HBeAg-positive CHB patients exhibited elevated circulating HBV RNA levels compared to those achieving MVR.

Electric field control of spin-orbit torque in annealed Ta/CoFeB/HfOxheterostructures via interfacial oxidation modulation.

Electric field control of spin-orbit torque (SOT) exhibits promising potential in advanced spintronic devices through interfacial modulation. In this work, we investigate the influence of electric field and interfacial oxidation on SOT efficiency in annealed Ta/CoFeB/HfOxheterostructures. By varying annealing temperatures, the damping-like SOT efficiency reaches its peak at the annealing temperature of 320 °C, with an 80% field-free magnetization switching ratio induced by SOT having been demonstrated. This enhancement is ascribed to the annealing-induced modulation of oxygen ion migration at the CoFeB/HfOxinterface. By applying voltages across the Ta/CoFeB/HfOxheterostructures, which drives the O2‒migration across the interface, a reversible, bipolar, and non-volatile modulation of SOT efficiency was observed. The collective influence of annealing temperature and electric field effects on SOT carried out in this work provides an effective approach into facilitating the optimization and control of SOT in spintronic devices.

[Based on CT imaging, surgical approach selection for frontal and ethmoid sinus osteoma].

Objective:To investigate the criteria for selecting surgical approaches for frontal and ethmoid sinus osteomas of different locations and sizes on CT imaging. Methods:Using sagittal and coronal CT images, the following lines were delineated: the F-line（a horizontal line passing nasofrontal beak）, the M-line（a vertical line passing paries medialis orbitae）, and the P-line（a vertical line passing the center of the pupil）. Classification of frontal and ethmoid sinus osteomas was based on their relationship with these lines. Appropriate surgical approaches were selected, including pure endoscopic approaches, endoscopic combined with eyebrow incision approach, and endoscopic combined with coronal incision approach. This method was applied to a single center at the Third Affiliated Hospital of Sun Yat-sen University for endoscopic resection of frontal and ethmoid sinus osteoma. Case Data: Sixteen cases of ethmoid sinus osteomas were treated from January 2020 to September 2023. Among these cases, there were 9 males and 7 females, with ages ranging from 18 to 69 years, and a median age of 48 years. Results:Thirteen cases underwent pure endoscopic resection of the osteoma, while in three cases, a combined approach was utilized. Among the combined approach cases, two exceeded both the M-line and the F-line but did not cross the P-line; therefore, they underwent endoscopic combined with eyebrow incision approach. One case exceeded all three lines and thus underwent endoscopic combined with coronal incision. In all cases, complete resection of the osteoma was achieved as per preoperative planning, and none of the patients experienced significant postoperative complications. Conclusion:For frontal and ethmoid sinus osteomas, it is advisable to perform a thorough preoperative radiological assessment. Based on the size of the osteoma and its relationship to the three lines, an appropriate surgical approach should be chosen to optimize the diagnostic and treatment plan.

LARP7 overexpression alleviates aortic senescence and atherosclerosis.

Atherosclerosis, characterized by the accumulation of lipid plaques on the inner walls of arteries, is the leading cause of heart attack, stroke and severe ischemic injuries. Senescent cells have been found to accumulate within atherosclerotic lesions and contribute to the progression of atherosclerosis. In our previous study, we discovered that suppressing Larp7 accelerates senescence by inhibiting Sirt1 activity, resulting in increased atherosclerosis in high-fat diet (HFD) fed and ApoE deficient (ApoEKO) mice. However, there has been no direct evidence demonstrating Larp7 per se could attenuate atherosclerosis. To this end, we generated a tetO-controlled and Cre-activated Larp7 gain-of-function mouse. Through RT-PCR and western blotting, we confirmed Larp7 overexpression in the aortas of HFD-fed ApoEKO; Larp7tetO mice. Larp7 overexpression led to increased Sirt1 activity and decreased cellular senescence signals mediated by p53/p65 in the aortas. Additionally, Larp7 overexpression reduced the presence of p16-positive senescent cells in the aortic lesions. Furthermore, Larp7 overexpression resulted in a decrease in pro-inflammatory macrophages and SASP factors. Consequently, Larp7 overexpression led to a reduction in the area of atherosclerotic lesions in HFD-fed ApoEKO; Larp7tetO mice. In summary, our study provides evidence that Larp7 overexpression holds promise as an approach to inhibit cellular senescence and prevent atherosclerosis.

A urethral leiomyoma presenting with dysuria: A rare case report.

RATIONALE: Leiomyoma is a benign smooth muscle tumor which is rarely found in urethra. We hereby report a case of a 44-year-old female who presented with complaints of dysuria. PATIENT CONCERNS: A 44-year-old female patient presented to the urology outpatient clinic with symptoms of dysuria. The patient described the presence of a protrusion from the urethra during urination. DIAGNOSIS: Urethral leiomyoma. INTERVENTIONS: Physical examination confirmed a solid urethral mass. CT scan and USG reports indicated that the mass originated from the mid-urethra with vascularity at the base. We performed a complete resection of the urethral mass. The patient was discharged after 3 days of observation. OUTCOME: During a follow-up after 1 month, the patient reported improved urinary flow and no occurrence of hematuria. The patient recovered well after discharge. LESSON: Urethral leiomyoma is a rare benign tumor that is often misdiagnosed in clinical practice. Diagnosis requires careful clinical examination. Surgical removal usually works well. It is important to remember that in some cases of acute urinary retention, it can be caused by a complete obstruction of a mass in the urethra. Urologists should be more cautious and experienced in handling such cases.

Allele-Specific Suppression of Variant MHC With High-Precision RNA Nuclease CRISPR-Cas13d Prevents Hypertrophic Cardiomyopathy.

BACKGROUND: Familial hypertrophic cardiomyopathy has severe clinical complications of heart failure, arrhythmia, and sudden cardiac death. Heterozygous single nucleotide variants (SNVs) of sarcomere genes such as MYH7 are the leading cause of this type of disease. CRISPR-Cas13 (clustered regularly interspaced short palindromic repeats and their associated protein 13) is an emerging gene therapy approach for treating genetic disorders, but its therapeutic potential in genetic cardiomyopathy remains unexplored. METHODS: We developed a sensitive allelic point mutation reporter system to screen the mutagenic variants of Cas13d. On the basis of Cas13d homology structure, we rationally designed a series of Cas13d variants and obtained a high-precision Cas13d variant (hpCas13d) that specifically cleaves the MYH7 variant RNAs containing 1 allelic SNV. We validated the high precision and low collateral cleavage activity of hpCas13d through various in vitro assays. We generated 2 HCM mouse models bearing distinct MYH7 SNVs and used adenovirus-associated virus serotype 9 to deliver hpCas13d specifically to the cardiomyocytes. We performed a large-scale library screening to assess the potency of hpCas13d in resolving 45 human MYH7 allelic pathogenic SNVs. RESULTS: Wild-type Cas13d cannot distinguish and specifically cleave the heterozygous MYH7 allele with SNV. hpCas13d, with 3 amino acid substitutions, had minimized collateral RNase activity and was able to resolve various human MYH7 pathological sequence variations that cause hypertrophic cardiomyopathy. In vivo application of hpCas13d to 2 hypertrophic cardiomyopathy models caused by distinct human MYH7 analogous sequence variations specifically suppressed the altered allele and prevented cardiac hypertrophy. CONCLUSIONS: Our study unveils the great potential of CRISPR-Cas nucleases with high precision in treating inheritable cardiomyopathy and opens a new avenue for therapeutic management of inherited cardiac diseases.