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Summary: Vascular smooth muscle cells (VSMCs) can transdifferentiate into macrophage-like cells in the context of sustained inflammatory injury, which drives vascular hyperplasia and atherosclerotic complications. Using single-cell RNA sequencing, we identify that macrophage-like VSMCs are the key cell population in mouse neointimal hyperplasia. Sex-determining region Y (SRY)-related HMG-box gene 10 (Sox10) upregulation is associated with macrophage-like VSMC accumulation and pyroptosis in vitro and in the neointimal hyperplasia of mice. Tumor necrosis factor α (TNF-α)-induced Sox10 lactylation in a phosphorylation-dependent manner by PI3K/AKT signaling drives transcriptional programs of VSMC transdifferentiation, contributing to pyroptosis. The regulator of G protein signaling 5 (RGS5) interacts with AKT and blocks PI3K/AKT signaling and Sox10 phosphorylation at S24. Sox10 silencing mitigates vascular inflammation and forestalls neointimal hyperplasia in RGS5 knockout mice. Collectively, this study shows that Sox10 is a regulator of vascular inflammation and a potential control point in inflammation-related vascular disease.

Vascular smooth muscle cell (VSMC) senescence is a major driver of neointimal formation. We have demonstrated that circ-Sirt1 derived from the SIRT1 gene suppressed VSMC inflammation and neointimal formation. However, the effect of circ-Sirt1 inhibiting inflammation on VSMC senescence during neointimal hyperplasia remains to be elucidated. Here, we showed that circ-Sirt1 was highly expressed in young and healthy arteries, which was decreased in aged arteries and neointima of humans and mice. Overexpression of circ-Sirt1 delayed Ang II-induced VSMC senescence in vitro and ameliorated neointimal hyperplasia in vivo. Mechanically, circ-Sirt1 inhibited p53 activity at the levels of transcription and post-translation modulation. In detail, circ-Sirt1, on the one hand, interacted with and held p53 to block its nuclear translocation, and on the other hand, promoted SIRT1-mediated p53 deacetylation and inactivation. In conclusion, our data suggest that circ-Sirt1 is a novel p53 repressor in response senescence-inducing stimuli, and targeting circ-Sirt1 may be a promising approach to ameliorating aging-related vascular disease.

The congenital intellectual disability (ID)-causing gene mutations remain largely unclear, although many genetic variations might relate to ID. We screened gene mutations in Chinese Han children suffering from severe ID and found a single-nucleotide polymorphism (SNP) in the 5′-untranslated region (5′-UTR) of fibroblast growth factor 13 (FGF13) mRNA (NM_001139500.1:c.-32c>G) shared by three male children. In both HEK293 cells and patient-derived induced pluripotent stem cells, this SNP reduced the translation of FGF13, which stabilizes microtubules in developing neurons. Mice carrying the homologous point mutation in 5′-UTR of Fgf13 showed delayed neuronal migration during cortical development, and weakened learning and memory. Furthermore, this SNP reduced the interaction between FGF13 5′-UTR and polypyrimidine-tract-binding protein 2 (PTBP2), which was required for FGF13 translation in cortical neurons. Thus, this 5′-UTR SNP of FGF13 interferes with the translational process of FGF13 and causes deficits in brain development and cognitive functions.

In order to clarify the relations between the different initial states and safety of pipeline shutdown during the forward and reverse transportation process. Analyze the flow state and innovatively divide forward and reverse transportation process into 4 phase: forward cold oil control phase, forward hot oil control phase, reverse cold oil control phase, reverse hot oil control phase. Then, based on the analysis of the characteristics of pipeline temperature drop in different above phase, the safety of different initial state of pipeline shutdown is qualitatively analyzed from the view of oil temperature changes. Finally, define a new parameter “Safe Shutdown Probability ϕ'' to describe and quantitatively analyze the safety of different initial phase of pipeline shutdown during forward and reverse transportation. The analysis results show that the shutdown safety is lowest when ϕ=±0 and highest when ϕ=±1.

To address the performance bottleneck in metal-based interconnects, hybrid optical network-on-chip (HONoC) has emerged as a new alternative. However, as the size of the HONoC grows, insertion loss and crosstalk noise increase, leading to excessive laser source output power and performance degradation. Therefore, we propose a low-power scalable HONoC architecture by incorporating semiconductor optical amplifiers (SOAs). An SOA placement algorithm is developed considering insertion loss and crosstalk noise. Furthermore, we establish a worst-case crosstalk noise model of SOA-enabled HONoC and induce optimized SOA gains with respect to power consumption and performance, respectively. Extensive simulations for worst-case signal-to-noise ratio (SNR) and power consumption are conducted under various traffic patterns and different network sizes. Simulation results show that the proposed SOA-enabled HONoC architecture and the associated algorithm help sustain the performance as network size increases without additional laser source power.

Zanthoxylum species have long been utilized in traditional medicine; among their various properties, they provide an analgesic effect. Central to this medicinal application are alkamides, a class of alkaloids characterized by their unsaturated fatty acid chains. These compounds are particularly noted for their distinctive alleviation of tingling and numbing effects, which are beneficial in dental pain management and local anesthesia. This review synthesizes the existing phytochemical research on alkamides derived from 11 Z. species, focusing on their chemical properties, pharmacodynamics and clinical implications. The analysis includes an examination of the structure–activity relationships (SARs), pharmacokinetics and mechanisms by which these compounds modulate sensations such as pungency and numbness, contributing to their analgesic and local anesthetic efficacy. This systemic review identifies significant research gaps, including the need for comprehensive evaluations of alkamide efficacy, detailed explorations of their pharmacological mechanisms and expanded clinical applications. These areas represent key opportunities for future investigations to enhance the understanding and utilization of alkamides in medical treatments. [ABSTRACT FROM AUTHOR]

In order to accurately predict the change of mine wireless network flow, ensure the safe and stable operation of underground wireless network and ensure the safety of mine production. Based on the analysis of the traffic characteristics of wireless network, this paper proposes a kind of CL-FCCNet, which is a traffic prediction model based on residual network （ＲｅｓＮｅｔｓ） and circular neural network（ＲＮＮ）. The prediction model can forecast traffic for complex wireless network working environment, model the temporal and spatial characteristics of traffic data, and help to realize the abnormal automatic alarm of traffic monitoring. The experimental results show that the prediction effect of the model is improved compared with the existing prediction methods.

This study investigated the effects of cilostazol on motor dysfunction, spinal motor neuron abnormalities, and schwannopathy in rats with diabetes. Diabetes mellitus (DM) was induced in rats via femoral intravenous streptozotocin (STZ) injection (60 mg/kg). After successful DM induction, cilostazol was administered on day 15 via oral gavage (100 mg/kg/day) for 6 weeks until sacrifice. Behavioral assays, including motor function, were performed weekly. The sciatic nerve, L5 spinal cord, and spinal ventral root were collected to evaluate the expression of the glial fibrillary acidic protein (GFAP), myelin protein zero (P0), and choline acetyltransferase (ChAT) by immunofluorescence and Western blotting. DM rats displayed decreased running speeds, running distances, and toe spread but increased foot pressure. In addition, loss of non-myelinating Schwann cells and myelin sheaths was observed in the sciatic nerve and L5 spinal ventral root. Reduced numbers of motor neurons were also found in the L5 spinal ventral horn. Cilostazol administration significantly potentiated running speed and distance; increased hind paw toe spread; and decreased foot pressure. In the sciatic nerve and L5 spinal ventral root, cilostazol treatment significantly improved non-myelinated Schwann cells and increased myelin mass. ChAT expression in motor neurons in the spinal ventral horn was improved, but not significantly. Cilostazol administration may protect sensorimotor function in diabetic rats. [ABSTRACT FROM AUTHOR]

Background: Upper tract urothelial carcinoma (UTUC) is a rare tumor with extraordinarily different features between Eastern and Western countries. Vascular endothelial growth factor‐A (VEGFA) was originally identified as a secreted signaling protein and regulator of vascular development and cancer progression. In this study, we aimed to elucidate the molecular mechanisms underlying the regulation of VEGFA by microRNA in UTUC. Methods: VEGFA expression was evaluated by immunohistochemistry in 140 human UTUC tissue samples. Next, we assessed the regulatory relationship between VEGFA and miR‐299‐3p by real‐time PCR, western blotting, ELISA and dual‐luciferase reporter assays using two UTUC cell lines. The role of miR‐299‐3p/VEGFA in cell proliferation, motility, invasion, and tube formation was analyzed in vitro. Results: High VEGFA expression was significantly associated with tumor stage, grade, distant metastasis and cancer‐related death and correlated with poor progression‐free and cancer‐specific survival. VEGFA knockdown repressed proliferation, migration, invasion and angiogenesis in UTUC cell lines. miR‐299‐3p significantly reduced VEGFA protein expression and miR‐299‐3p overexpression inhibited VEGFA mRNA and protein expression by directly targeting its 3′‐UTR. Functional studies indicated that VEGFA overexpression reversed the miR‐299‐3p‐mediated suppression of tumor cell proliferation, migration, invasion and angiogenesis. In addition, miR‐299‐3p/VEGFA suppressed cellular functions in UTUC by modulating the expression of P18 and cyclin E2. Conclusions: Our findings suggest that miR‐299‐3p possibly suppresses UTUC cell proliferation, motility, invasion and angiogenesis via VEGFA. VEGFA may act as a prognostic predictor, and both VEGFA and miR‐299‐3p could be potential therapeutic targets for UTUC. [ABSTRACT FROM AUTHOR]

Aim: The tumor staging of colorectal cancer (CRC) plays a significant role in both treatment and prognosis, impacting surgical planning and adjuvant therapy decisions. Currently, the staging of CRC is based on the TNM system developed by the American Joint Committee on Cancer. Prior studies have suggested that survival rates and recurrent rates of T4a tumors appear to be worse than that of T4b tumors, although there is currently no consensus. Therefore, we collected patient data from Taichung Veterans General Hospital over the past decade in order to conduct further research. Method: Between 2010 and 2018, a total of 5760 newly diagnosed CRC patients were seen at the hospital. To eliminate the influence of any local lymph node involvement or distant organ metastasis on the research results, we focused on patients with pathologic Stage IIc disease (T4a-bN0M0). Patients with rectal cancer who had received neoadjuvant concurrent chemoradiotherapy were excluded. Ultimately, 132 patients were included in this study. A multivariate Cox regression analysis was conducted to identify independent risk factors for both 10-year cancer-specific survival (CSS) and overall survival (OS). Results: A total of 132 patients were included in the study, with 90 classified as T4a and 42 as T4b. The 10-year CSS for pT4a and pT4b was 72.5% and 56.5%, respectively, with a p-value of 0.011. The 10-year OS for pT4a and pT4b was 48.4% and 42.5%, respectively, with a p-value of 0.086. There was no significant difference in the site of first recurrence between the pT4a and pT4b groups (p-value = 0.936). Overall, patients who received adjuvant chemotherapy therapy had a significantly better prognosis (p-value < 0.05). However, there was no significant difference in prognosis between oral 5-FU and FOLFOX. Conclusion: Based on our data, patients diagnosed with pathologic T4aN0M0 CRC appeared to experience a trend toward better 10-year OS when compared to those with T4bN0M0 disease, but this trend lacks statistical significance. Patients with locally advanced Stage II colon cancer clearly benefited from adjuvant chemotherapy therapy; therefore, FOLFOX may not necessarily be required.

Q fever is a zoonosis caused by infection with Coxiella burnetii, a gram-negative bacterium and obligate intracellular pathogen. The major animal reservoirs are goats, sheep, and cattle. Humans are infected [...]

Introduction Quinidine is categorized as a class IA antiarrhythmic drug because it slows the rapid upstroke of cardiac action potential by blocking the inward sodium current and by prolonged re-polarization [...], Purpose Multi-modality electrophysiological techniques were performed to assess the effects of quinidine on peripheral nerve conduction. Methods Twenty-seven rats were treated with 1, 3, and 5 µmol quinidine in 0.1 ml 5% glucose. The mixed-nerve somato-sensory evoked potential (M-SSEP), dermatomal-SSEP (D-SSEP), and compound muscle action potentials (CMAP) were evoked and recorded. After positioning Gelfoam strips saturated with quinidine and 5% glucose around the left and right sciatic nerves, potentials were measured at baseline, immediately after treatment, every 15 min for the 1st hour, and every 30 min for the next 3 h. After 2 weeks, the walking behaviors and potentials were again analyzed and myelinated fibers in the sciatic nerve were counted. Results Quinidine applied directly to sciatic nerves reduced the amplitude and prolonged the latency in SSEPs and CMAP, compared to baseline and the contralateral right limbs (controls). This persisted for at least 4 h. After 2 weeks, electrophysiological tests and walking behavior showed no significant difference between the controls and experimental limbs. There was also no difference in the number of myelinated fibers in the sciatic nerves. Conclusions Quinidine decreases amplitude and prolongs latency in the sciatic nerve in a dose-related manner without local neural toxicity. Keywords Quinidine * Sciatic nerve * Somato-sensory evoked potential * Compound muscle action potentials