ITIH4 reversed the effects of thrombin on VSMCs stiffness via JNK and ERK signaling pathway.

Vascular smooth muscle cell (VSMCs) is one of the important cell types in artery. VSMCs stiffening may regulate vascular stiffness and contribute to the development of vulnerable plaques. Thrombin, an enzyme in coagulation system, is involved in pathological processes of atherosclerosis. Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) plays an important role in regulating inflammation and may have cardiovascular protective effect. Therefore, the elucidation of the mechanisms underlying ITIH4-mediated VSMCs stiffening helps to provide new ideas and potential targets for the diagnosis and treatment of atherosclerosis. In this study, we used specific ITIH4 expression vector and siRNA methods to transfect VSMCs. Our results found that ITIH4 expression increased VSMCs stiffness, meanwhile, ITIH4 siRNA decreased VSMCs stiffness. ITIH4 increased acetylated α-tubulin and inhibited ERK1/2 and JNK, but not P38 MAPK. ERK inhibitor (PD98059) or JNK inhibitor (SP600125) treatment increased acetylated α-tubulin expression and cell stiffness in VSMCs. ITIH4 was downregulated by thrombin treatment, ITIH4 partly reversed the effect of thrombin on acetylated α-tubulin and VSMCs stiffness. These results indicated that ITIH4 regulated acetylated α-tubulin expression in VSMCs and was against the effects of thrombin on VSMCs stiffness. JNK and ERK signaling pathways were proved to participate in this process.

[Advantage analysis of modified day surgery procedure for concealed penis].

OBJECTIVE: The modified day surgery procedure was compared with traditional inpatient procedure and standard day surgery procedure of concealed penile surgery to investigate its advantages, as well as the feasibility of promoting it in our country. METHODS: Retrospective analyzing the clinical data between 135 cases of the concealed penis in children who underwent modified day surgery (day group) and 101 cases who underwent hospitalization surgery (hospitalization group) at the Second Hospital of Hebei Medical University and the results of follow-up.The modified day surgery procedure involves the establishment of dedicated day wards in each surgical department, where the patient's condition is monitored until 8 o'clock the following morning to assess their discharge eligibility.The children's clinical data was divided into two groups to compare clinical parameters, including age at surgery, bleeding volume, operation time, hospitalization expenses, day of hospitalization, and the occurrence of short-term complications before the initial dressing change after surgery.The satisfaction survey of the children was conducted among three distinct groups: the modified day group, the standard day group, and the hospitalization group enabling a comparison of satisfaction levels among these groups. RESULTS: The mean ages of the inpatient and day surgery groups were 8.92±4.42 years old and 11.85±4.43 years old, respectively. No significant differences were observed between these two groups regarding operation time, bleeding volume, and postoperative complications (P>0.05). Compared to the inpatient group, the mean inpatient time and the hospitalization cost of the day group decreased by 69% and 27%, respectively (P<0.05). The patients in the modified procedure group reported the highest satisfaction among the three groups. CONCLUSION: Modified day surgery procedure offers advantages over the standard day surgery procedure and traditional inpatient surgical procedures for the operative treatment of the concealed penis, which makes it suitable for large-scale popularization in China.

ITIH4 is a predictor for coronary thrombus in coronary arteriography patients.

Aim: To explore potential value of inter-alpha-trypsin inhibitor heavy chain-4 (ITIH4) for coronary artery disease (CAD) diagnosis. Patients & methods: We recruited the patients who received coronary arteriography (CAG) examination. The enzyme-linked immunosorbent assay was used to detect plasma ITIH4. Results: ITIH4 level was lower expression in CAD patients than that in patients of control group, and was negatively correlated with C-reactive protein (CRP). ITIH4 level is no differences between ST-elevated myocardial infarction (STEMI) and non-ST-elevated myocardial infarction (NSTEMI) patients. However, its expression was significantly correlated with D-Dimer and thrombin time, and the logistic analysis confirmed predictive value of ITIH4 for visible thrombus in coronary. Conclusion: ITIH4 may be a useful biomarker in CAD diagnosis, and to predict visible thrombus in coronary.

What is this summary about? ITIH4 is present in human plasma and related to several diseases. Coronary artery disease (CAD) is one of the most popular diseases in the world. We test the diagnosis value of ITIH4 in CAD patients.What were the results? ITIH4 level was lower in CAD patients than that in control patients. ITIH4 was correlated with C-reactive protein. ITIH4 may play a role in clotting system. ITIH4 was also correlated with D-Dimer and thrombin time. ITIH4 level in thrombus patients was lower than that in without thrombus patients. ITIH4 could be used to predict coronary visible thrombus.What do the results mean? ITIH4 may be a useful diagnosis biomarker in CAD patients.

Effect of static pressure on ultrasonic liquid phase exfoliation of few-layer graphene.

Ultrasonic Liquid Phase Exfoliation (LPE) has gathered attention from both scientific and industrial communities for its accessibility and cost-effectiveness in producing graphene. However, this technique has faced challenges such as low yield and long production time. In this study, we developed a cyclic ultrasonication system to exfoliate expanded graphite (EG) by applying static pressure to a flow chamber to address these challenges. Using deionized water (DIW) as solvent and polyvinylpyrrolidone (PVP) as dispersion, we obtained graphene slurries with an average lateral size of 7 µm and averaged number of layers of 3.5 layers, after 40 min of ultrasonication. After centrifugation, the yield of single and bilayer graphene was approximately 16 %. The findings showed that regulating hydrostatic pressure can effectively affect the lateral size and number of layers of few-layer graphene. The proposed method is of good potential for scaled-up production of few-layer graphene.

Design and Effect of Resonant Ultrasonic Vibration-Assisted Laser Cladding (R-UVALC) on AlCrFeMnNi High-Entropy Alloy.

The design of the resonant ultrasonic vibration-assisted laser cladding (R-UVALC) setup involved employing finite element analysis (FEA) to simulate the ultrasonic transducer, horn, and workpiece in a resonance state. The impact of R-UVALC on AlCrFeMnNi high-entropy alloys was assessed using various ultrasonic vibration amplitudes of 0, 5, 10, and 15 µm, with a constant frequency of 20 kHz. Ultrasonic vibrations reduced pores and cracks and increased the clad breadth, melt pool wetting angle, and laser-clad layer consistency. The columnar elongated grains in proximity to the substrate surface underwent a size reduction and transformed into grains with a more equiaxed shape with the utilization of ultrasonic vibrations at an amplitude of 5 µm. Laser cladding performed without ultrasonic vibrations yields two phases: face-centered cubic (FCC) and body-centered cubic (BCC). However, when the coating is exposed to ultrasonic vibrations with an amplitude of 5 µm, it forms a solitary body-centered cubic (BCC) phase. The microhardness tripled compared to the substrate, and the most significant microhardness value was achieved at 5 µm of ultrasonic vibration. The friction coefficient was assessed at an ambient temperature, revealing that an ultrasonic amplitude yields the lowest friction coefficient, demonstrating the excellent wear resistance properties of the coating. The analysis of the 3D surface profile of the wear indicates that the use of ultrasonic aid with a 5 µm amplitude leads to reduced depth of scars, and the primary wear mechanism observed is abrasive and oxidative wear with fewer grooves and debris. In addition, XPS analysis revealed the presence of metal components in an oxidized condition, suggesting that the wear process is oxidative in nature. Integrating the R-UVALC setup into a resonance state can significantly enhance the efficiency of the laser cladding process in the laser cladding field.

Binder assisted graphene derivatives as lubricants in copper: Improved tribological performance for industrial application.

Originally derived from graphite, high-quality single-layer graphene is an excellent anti-wear and -friction additive in metal matrix. Here, the tribological performance of 3 different commercialized graphene derivatives (e.g., graphene oxide [GO], reduced graphene oxide [RGO], and graphene nanoplatelet [GNP]) as additives in a Cu matrix, were investigated from an industrial perspective. To increase the interaction of graphene derivatives with Cu particles, and addressing the aggregation problem of the graphene derivatives, different binders (polyvinyl alcohol [PVA] and cellulose nanocrystals [CNC]) were introduced into the system. Benefiting from such a strategy, a uniform distribution of the graphene derivatives in Cu matrix was achieved with graphene loading up to 5 wt %. After high-temperature sintering, the graphene is preserved and well distributed in the Cu matrix. It was found that the GNP-containing sample shows the most stable friction coefficient behavior. However, GO and RGO also improve the tribological performance of Cu under different circumstances.

Research progress of acupuncture and moxibustion for the enhanced synergism of chemotherapy. / é’ˆç¸ååŒåŒ–ç–—å®žçŽ°å¢žæ•ˆçš„ç ”ç©¶è¿›å±•.

The application of acupuncture and moxibustion in alleviating the adverse effects of chemotherapy drugs has been widely recognized at home and abroad, but the studies have been rarely summarized for the enhanced anti-tumor effect and its mechanism of acupuncture and moxibustion to synergize the chemotherapy drugs. This paper reviewed the clinical and basic studies on the synergism of chemotherapy with acupuncture and moxibustion in recent years. It was found that chemotherapy synergized with acupuncture and moxibustion can suppress cancer to a certain extent and improve the quality of life in patients. The effect mechanism of acupuncture and moxibustion combined with chemotherapy drugs is related to promoting tumor cell apoptosis, improving the immune and vascular microenvironment, and advancing chemotherapy drug enrichment on the affected area. It provides the evidences and ideas for enhancing the effect of chemotherapy by delivering acupuncture and moxibustion as an adjuvant therapy.

Synergistic antitumor activity of baicalein combined with almonertinib in almonertinib-resistant non-small cell lung cancer cells through the reactive oxygen species-mediated PI3K/Akt pathway.

Introduction: Almonertinib is an important third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) exhibiting high selectivity to EGFR-sensitizing and T790M-resistant mutations. Almonertinib resistance is a major obstacle in clinical use. Baicalein possesses antitumor properties, but its mechanism of antitumor action against almonertinib-resistant non-small cell lung cancer (NSCLC) remains unelucidated. Methods: CCK-8 assay was used to examine the survival rate of H1975/AR and HCC827/AR cells following treatment for 24 h with different concentrations of baicalein, almonertinib or their combination. The changes in colony formation ability, apoptosis, and intracellular reactive oxygen species (ROS) levels of the treated cells were analyzed using colony formation assay and flow cytometry. Western blotting was performed to detect the changes in protein expressions in the cells. The effects of pre-treatment with NAC on proliferation, apoptosis, and PI3K/Akt signaling pathway were observed in baicalein- and/or almonertinib-treated cells. A nude mouse model bearing subcutaneous HCC827/AR cell xenograft were treated with baicalein (20 mg/kg) or almonertinib (15 mg/kg), and the tumor volume and body mass changes was measured. Results: Both baicalein and almonertinib represses the viability of HCC827/AR and H1975/AR cells in a concentration-dependent manner. Compared with baicalein or almonertinib alone, the combined application of the two drugs dramatically attenuates cell proliferation; triggers apoptosis; causes cleavage of Caspase-3, PARP, and Caspase-9; downregulates the protein expressions of p-PI3K and p-Akt; and significantly inhibits tumor growth in nude mice. Furthermore, baicalein combined with almonertinib results in massive accumulation of reactive oxygen species (ROS) and preincubation with N-acetyl-L-cysteine (ROS remover) prevents proliferation as well as inhibits apoptosis induction, with partial recovery of the decline of p-PI3K and p-Akt. Discussion: The combination of baicalein and almonertinib can improve the antitumor activity in almonertinib-resistant NSCLC through the ROS-mediated PI3K/Akt pathway.

A novel tissue-engineered corneal epithelium based on ultra-thin amniotic membrane and mesenchymal stem cells.

Currently, in vitro cultured corneal epithelial transplantation is effective in treating limbal stem cell dysfunction (LSCD). Selecting carriers is crucial for constructing the corneal epithelium through tissue engineering. In this study, the traditional amniotic membrane (AM) was modified, and mesenchymal stem cells (MSCs) were inoculated into the ultra-thin amniotic membrane (UAM) stroma to construct a novel UAM-MSC tissue-engineered corneal epithelial carrier, that could effectively simulate the limbal stem cells (LSCs) microenvironment. The structure of different carriers cultured tissue-engineered corneal epithelium and the managed rabbit LSCD model corneas were observed through hematoxylin-eosin staining. Cell phenotypes were evaluated through fluorescence staining, Western blotting, and RT-qPCR. Additionally, cell junction genes and expression markers related to anti-neovascularization were evaluated using RT-qPCR. Corneal epithelium cell junctions were observed via an electron microscope. The tissue-engineered corneal epithelium culture medium was analyzed through mass spectrometry. Tissue-engineered corneal epithelial cells expanded by LSCs on UAM-MSCs had good transparency. Simultaneously, progenitor cell (K14, PNCA, p63) and corneal epithelial (PAX6) gene expression in tissue-engineered corneal epithelium constructed using UAM-MSCs was higher than that in corneal epithelial cells amplified by UAM and de-epithelialized amniotic membrane. Electron microscopy revealed that corneal epithelial cells grafted with UAM-MSCs were closely connected. In conclusion, the UAM-MSCs vector we constructed could better simulate the limbal microenvironment; the cultured tissue-engineered corneal epithelium had better transparency, anti-neovascularization properties, closer intercellular connections, and closer resemblance to the natural corneal epithelial tissue phenotype.

FGL1: a novel biomarker and target for non-small cell lung cancer, promoting tumor progression and metastasis through KDM4A/STAT3 transcription mechanism.

Non-small cell lung cancer (NSCLC) is characterized by a high incidence rate and poor prognosis worldwide. A deeper insight into the pathogenesis of NSCLC and identification of novel therapeutic targets are essential to improve the prognosis of NSCLC. In this study, we revealed that fibrinogen-like protein 1 (FGL1) promotes proliferation, migration, and invasion of NSCLC cells. Mechanistically, we found that Stat3 acts as a transcription factor and can be recruited to the FGL1 promoter, enhancing FGL1 promoter activity. Lysine-specific demethylase 4A (KDM4A) interacts with Stat3 and facilitates the removal of methyl groups from H3K9me3, thereby enhancing Stat3-mediated transcription of FGL1. Furthermore, we observed that Stat3 and KDM4A promote NSCLC cell proliferation, migration, and invasion partly by upregulating FGL1 expression. Additionally, the expression of FGL1 was significantly higher in cancer tissues (n = 90) than in adjacent non-cancerous tissues (n = 90). Furthermore, patients with high FGL1 expression had a shorter overall survival (OS) compared to those with low FGL1 expression. We measured the expression levels of FGL1 on circulating tumor cells (CTCs) in 65 patients and found that patients with a dynamic decrease in FGL1 expression on CTCs exhibited a better therapeutic response. These findings suggest that the dynamic changes in FGL1 expression can serve as a potential biomarker for predicting treatment efficacy in NSCLC. Overall, this study revealed the significant role and regulatory mechanisms of FGL1 in the development of NSCLC, suggesting its potential as a therapeutic target for patients with NSCLC. Future studies should provide more personalized and effective treatment options for patients with NSCLC to improve clinical outcomes.

LncRNA-599554 sponges miR-15a-5p to contribute inductive ability of dermal papilla cells through positive regulation of the expression of Wnt3a in cashmere goat

BACKGROUND: Long non-coding RNAs (lncRNAs), as post-transcriptional regulators, were thought to function in the inductive property of dermal papilla cells (DPCs) in cashmere goat. Previously, lncRNA-599554 was identified in secondary hair follicle (SHF) of cashmere goat, but its functional significance is unknown. RESULTS: In the present investigation, we verified that lncRNA-599554 had significantly higher expression at the anagen dermal papilla of cashmere goat SHF than that at telogen. Based on overexpression and knockdown techniques, we found that lncRNA-599554 contributes the inductive property of DPCs of cashmere goat, which was assessed by detecting the changes in the expression of several typical indictor genes in DPCs including ET-1, SCF, Versican, ALP, Lef1 and Ptc-1. Based on RNA pull-down assay, we verified that lncRNA-599554 directly interacted with chi-miR-15a-5p. Also, we showed that lncRNA-599554 positively regulated the Wnt3a expression in DPCs but which did not appear to involve its modulating of promoter methylation. Based on the use of Dual-luciferase reporter assays, our data indicated that lncRNA-599554 regulated the Wnt3a expression through chi-miR-15a-5p-mediated post-transcriptional level. CONCLUSIONS: We showed that lncRNA-599554 contributes the inductive property of DPCs in cashmere goat which might be achieved through sponging chi-miR-15b-5p to promote the Wnt3a expression. The results from the present investigation provided a novel insight into the functional mechanism of lncRNA-599554 in the SHF regeneration of cashmere goat along with the formation and growth of cashmere fiber.