Unveiling the Selectivity of Ru(II)-Catalyzed C-H Activation for Defluorinative Cyclization of 2-Arylbenzimidazole and Trifluoromethyl Diazo: A DFT Study.

The synthesis of monofluorinated heterocyclic compounds by C-H activation combined with defluorination is useful. Studies on the reaction mechanism and selectivity have shown that these processes play a positive role in promoting the development of monofluorinated reactions. Density functional theory (DFT) calculations were performed to investigate the mechanism and selectivity of Ru(II)-catalyzed 2-arylbenzimidazole with trifluoromethyl diazo. DFT calculations showed that C-H activation occurs through a concerted metalation/deprotonation (CMD) mechanism. After that, deprotonation and defluorinative cyclization are assisted by acetate and trifluoroethanol (TFE). Further mechanistic insights through noncovalent interaction (NCI) analysis were also obtained to elucidate the origin of the selectivity in the defluorination process.

Multi-instance learning of graph neural networks for aqueous pKa prediction.

MOTIVATION: The acid dissociation constant (pKa) is a critical parameter to reflect the ionization ability of chemical compounds and is widely applied in a variety of industries. However, the experimental determination of pKa is intricate and time-consuming, especially for the exact determination of micro-pKa information at the atomic level. Hence, a fast and accurate prediction of pKa values of chemical compounds is of broad interest. RESULTS: Here, we compiled a large-scale pKa dataset containing 16 595 compounds with 17 489 pKa values. Based on this dataset, a novel pKa prediction model, named Graph-pKa, was established using graph neural networks. Graph-pKa performed well on the prediction of macro-pKa values, with a mean absolute error around 0.55 and a coefficient of determination around 0.92 on the test dataset. Furthermore, combining multi-instance learning, Graph-pKa was also able to automatically deconvolute the predicted macro-pKa into discrete micro-pKa values. AVAILABILITY AND IMPLEMENTATION: The Graph-pKa model is now freely accessible via a web-based interface (https://pka.simm.ac.cn/). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Eugenol restrains abdominal aortic aneurysm progression with down-regulations on NF-κB and COX-2.

Abdominal aortic aneurysm (AAA) is a lethal disease without available medicine for treatment. This study aimed to evaluate the efficiency of eugenol (4-allyl-2-methoxyphenol) against AAA and the underlying mechanism. Eugenol is the major bioactive component of clove. A mouse AAA model was established through porcine pancreatic elastase (PPE) incubation peri-adventitially and 1% 3-aminopropanonitrile (BAPN) diet. Continuous AAA progression from day 0 to day 15 was observed after PPE plus BAPN treatment, according to the AAA diameter and histopathological evaluation. Accompanying with AAA progression, sustained increased expressions of CD68, COX-2 and NF-κB were observed through immunofluorescence assay. After elucidation the efficiency of eugenol against AAA progression by AAA diameter, hematoxylin-eosin staining and orcein staining, the down-regulations of eugenol on COX-2 and NF-κB were further detected by immunohistochemistry and western blot. Eugenol not only blocked AAA expansion and protected the integrity of aortic structure in a dose-dependent manner, but also held high oral bioavailability. Excellent efficiency, high oral bioavailability and down-regulation on COX-2/NF-κB endowed eugenol great potential for future AAA therapy.

Treatment of status epilepticus in pediatrics: curriculum learning combined with in-situ simulations.

BACKGROUND: Appropriate and timely treatment of status epilepticus (SE) reduces morbidity and mortality. Therefore, skill-based identification and management are critical for emergency physicians. PURPOSE: To assess whether the ability of training physicians, residents, nurses, and others to respond to SE as a team could be improved by using curriculum learning [Strategies and Tools to Enhance Performance and Patient Safety of Team (TeamSTEPPS) course training] combined with in-situ simulations of emergency department (ED) staff. APPROACH: A pre-training-post-training design was used on SE skills and teamwork skills. Emergency training, residents, and N1 and N2 nurses completed the SE skill and teamwork assessments (pre-training) through in-situ simulation. Next, the participating physicians and nurses attended the SE course [Strategies and Tools to Enhance Performance and Patient Safety of Team (TeamSTEPPS) course training], followed by conscious skill practice, including in-situ simulation drills every 20 days (eight times total) and deliberate practice in the simulator. The participants completed the SE skill and teamwork assessments (post-training) again in an in-situ simulation. Pre-training-post-training simulated SE skills and teamwork performance were assessed. The simulation training evaluation showed that the training process was reasonable, and the training medical staff had different degrees of benefit in increasing subject interest, improving operational skills, theoretical knowledge, and work self-confidence. FINDINGS: Sixty doctors and nurses participated in the intervention. When comparing the SE skills of 10 regular training physicians pre-training and post-training, their performance improved from 40% (interquartile range (IQR): 0-1) before training to 100% (IQR: 80.00-100) after training (p < 0.001). The teamwork ability of the 10 teams improved from 2.43 ± 0.09 before training to 3.16 ± 0.08 after training (p < 0.001). CONCLUSION: SE curriculum learning combined with in-situ simulation training provides the learners with SE identification and management knowledge in children and teamwork skills.

Discovery of novel 1,3,5-triazine derivatives as potent inhibitor of cervical cancer via dual inhibition of PI3K/mTOR.

This study describes the synthesis of novel 1,3,5-triazine derivatives as potent inhibitors of cervical cancer. The compounds were initially tested for inhibition of PI3K/mTOR, where they showed significant inhibitory activity. The top-ranking molecule (compound 6 h) was further tested against class I PI3K isoforms, such as PI3Kα, PI3Kß, PI3Kγ and PI3Kδ, where it showed the most significant activity against PI3Kα. Compound 6 h was then tested for anti-cancer activity against triple-negative breast cancer cells (MDA-MB321), human breast cancer cells (MCF-7), human cervical cancer cells (HeLa) and human liver cancer cells (HepG2), and it showed the greatest potency against HeLa cells. The effects of compound 6 h were further evaluated against the HeLa cells, where it showed significant attenuation of cell viability by inducing cell cycle arrest in the G1 phase. Compound 6 h induced apoptosis and reduced migration and invasion of HeLa cells. Western blotting analysis showed that 6 h inhibited PI3K and mTOR with positive modulation of Bcl-2 and Bax levels in HeLa cells. The effects of compound 6 h were also investigated in a tumour xenograft mouse model, where it showed reduction of tumour volume and weight. It also inhibited the PI3K/Akt/mTOR signalling cascade in xenograft tumour tissues, as evidenced by western blotting analysis. The results of the present study suggest the possible utility of the designed 1,3,5-triazine derivative as a potent inhibitor of cervical cancer.

LncRNA WEE2-AS1 promotes proliferation and inhibits apoptosis in triple negative breast cancer cells via regulating miR-32-5p/TOB1 axis.

Triple negative breast cancer (TNBC) is a malignant breast cancer subtype with poor prognosis. Recent studies have revealed the critical roles of dysregulated long non-coding RNAs (lncRNAs) in many cancer types, including TNBC. LncRNA WEE2 antisense RNA 1 (WEE2-AS1) has been reported to be able to promote the progression of hepatocellular carcinoma, but the function of WEE2-AS1 in TNBC is still unknown. Therefore, in this study, we specifically researched the role of WEE2-AS1 and probed its molecular mechanism in TNBC cells. Our results showed that WEE2-AS1 was up-regulated in TNBC cell lines, and WEE2-AS1 knockdown could inhibit TNBC cell proliferation, promote apoptosis, and suppress migration and invasion. Further, we found that miR-32-5p was down-regulated in TNBC cells and could be sponged by WEE2-AS1. Moreover, miR-32-5p could target its downstream gene transducer of ERBB2, 1 (TOB1), which was highly expressed and could play the oncogenic role in TNBC cells. Through rescue assays, we proved that WEE2-AS1/miR-32-5p/TOB1 axis could modulate cancer progression in TNBC cells. In conclusion, our results demonstrated the oncogenic function of lncRNA WEE2-AS1 in TNBC cells, providing a novel insight into TNBC therapy.

Inhibition of myeloperoxidase oxidant production by N-acetyl lysyltyrosylcysteine amide reduces brain damage in a murine model of stroke.

BACKGROUND: Oxidative stress plays an important and causal role in the mechanisms by which ischemia/reperfusion (I/R) injury increases brain damage after stroke. Accordingly, reducing oxidative stress has been proposed as a therapeutic strategy for limiting damage in the brain after stroke. Myeloperoxidase (MPO) is a highly potent oxidative enzyme that is capable of inducing both oxidative and nitrosative stress in vivo. METHODS: To determine if and the extent to which MPO-generated oxidants contribute to brain I/R injury, we treated mice subjected to middle cerebral artery occlusion (MCAO) with N-acetyl lysyltyrosylcysteine amide (KYC), a novel, specific and non-toxic inhibitor of MPO. Behavioral testing, ischemic damage, blood-brain-barrier disruption, apoptosis, neutrophils infiltration, microglia/macrophage activation, and MPO oxidation were analyzed within a 7-day period after MCAO. RESULTS: Our studies show that KYC treatment significantly reduces neurological severity scores, infarct size, IgG extravasation, neutrophil infiltration, loss of neurons, apoptosis, and microglia/macrophage activation in the brains of MCAO mice. Immunofluorescence studies show that KYC treatment reduces the formation of chlorotyrosine (ClTyr), a fingerprint biomarker of MPO oxidation, nitrotyrosine (NO2Tyr), and 4-hydroxynonenal (4HNE) in MCAO mice. All oxidative products colocalized with MPO in the infarcted brains, suggesting that MPO-generated oxidants are involved in forming the oxidative products. CONCLUSIONS: MPO-generated oxidants play detrimental roles in causing brain damage after stroke which is effectively reduced by KYC.

Cortactin and Exo70 mediated invasion of hepatoma carcinoma cells by MMP-9 secretion.

This study was aimed to evaluate the regulation mechanism of cortactin (CTTN) on matrix metalloproteinases 9 (MMP-9) and its relations with Exo70 in invasion of hepatoma carcinoma (HCC) cells. The expression levels of CTTN, Exo70 and MMP-9 were detected in normal hepatocytes and various HCC cells by real-time PCR. Then the migration and invasion ability of these cells was revealed by scratch and invasion assay. The effects of CTTN on MMP-9 and the ability of migration and invasion were evaluated by silence and overexpress CTTN. During this process, the expression of CTTN was detected by Western blot, the activity and concentration of MMP-9 in supernatant of culture medium was detected by zymography and ELISA assay. Besides, Exo70 was also inhibited to reveal its effects on MMP-9 and the migration and invasion ability of LM3. Increased expression of CTTN, MMP-9, Exo70, reduced scratch area and increased puncture cell numbers were found in HCC cells (p < 0.05). The expression of CTTN was significantly correlated with Exo70 and the migration and invasion ability of HCC (p < 0.05). In addition, the activity and concentration of MMP-9 were significantly affected by the expression level of CTTN, while the expression of MMP-9 was not influenced. Besides, Exo70-si also exhibited significantly inhibition effects on the activity and concentration of MMP-9 and puncture cell numbers (p < 0.05). A synergistic reaction may exhibited on CTTN and Exo70, which could mediate the secretion of MMPs thereby regulate tumor invasion.

GSTM1 polymorphism and lung cancer risk among East Asian populations: a meta-analysis.

GSTM1 gene encodes a key enzyme involved in the metabolism of xenobiotics, and its polymorphisms have been related to individual susceptibility to several malignancies. Many molecular epidemiological studies were performed to investigate the association between the GSTM1 null polymorphism and lung cancer susceptibility in East Asia. However, the results were inconsistent. In order to derive a more precise estimation, we conducted this meta-analysis involving 5,909 lung cancer cases and 7,067 controls from 35 studies. We used crude odds ratios (ORs) with 95 % confidence intervals (CIs) to assess the association between GSTM1 null genotype and the risk of lung cancer. Our study found that the GSTM1 null genotype appeared to be a significant risk factor for lung cancer in East Asia population (OR = 1.30, 95 % CI = 1.17-1.45, P heterogeneity < 0.0001, and I (2) = 54.0 %).

Decoy receptor 3 suppresses TLR2-mediated B cell activation by targeting NF-κB.

Decoy receptor 3 (DcR3) is a soluble protein in the TNFR superfamily. Its known ligands include Fas ligand, homologous to lymphotoxin, showing inducible expression, and competing with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes, TNF-like molecule 1A, and heparan sulfate proteoglycans. DcR3 has been reported to modulate the functions of T cells, dendritic cells, and macrophages; however, its role in regulating B cell activation is largely unknown. In this study, we found that the DcR3.Fc fusion protein bound to human and mouse B cells and suppressed the activation of B cells. DcR3.Fc attenuated Staphylococcus aureus, IgM-, Pam(3)CSK(4)-, and LPS-mediated B cell proliferation but did not affect cytokine-induced B cell growth. In the presence of these mitogens, DcR3.Fc did not induce B cell apoptosis, suggesting that DcR3 may inhibit the signal(s) important for B cell activation. Because the combination of Fas.Fc, LT-ßR.Fc (homologous to lymphotoxin, showing inducible expression, and competing with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes receptor), and DR3.Fc (TNF-like molecule 1A receptor) did not suppress B cell proliferation and because the biological effect of DcR3.Fc on B cells was not blocked by heparin, we hypothesize that a novel ligand(s) of DcR3 mediates its inhibitory activity on B cells. Moreover, we found that TLR2-stimulated NF-κB p65 activation and NF-κB-driven luciferase activity were attenuated by DcR3.Fc. The TLR2-induced cytokine production by B cells was consistently reduced by DcR3. These results imply that DcR3 may regulate B cell activation by suppressing the activation of NF-κB.

Potential synergistic anti-tumor activity between lenalidomide and sorafenib in hepatocellular carcinoma.

BACKGROUND AND AIM: The immune modulatory drug lenalidomide has shown promising anti-tumor activity in a clinical trial of patients with advanced hepatocellular carcinoma (HCC). The present study explored whether lenalidomide can enhance the anti-tumor activity of sorafenib, the standard molecular targeted therapy for HCC. METHODS: The anti-tumor efficacy of single-agent or combination treatment was measured by change in tumor volume and animal survival using an orthotopic liver cancer model. Distribution of T-cell subpopulations in tumor-infiltrating lymphocytes (TILs) and splenocytes derived from tumor-implanted mice was measured by flow cytometry. Depletion of relevant T-cell subpopulations or cytokines was done by co-administration of relevant antibodies with study drug treatment. Tumor cell apoptosis and tumor angiogenesis were measured by transferase deoxytidyl uridine end labeling assay and immunohistochemical study, respectively. RESULTS: Combination of sorafenib and lenalidomide produced significant synergistic anti-tumor efficacy in terms of tumor growth delay and animal survival. This synergistic effect was associated with a significant increase in interferon-γ expressing CD8(+) lymphocytes in TILs and a significantly higher number of granzyme- or perforin-expressing CD8(+) T cells, compared with vehicle- or single-agent treatment groups. Combination treatment significantly increased apoptotic tumor cells and vascular normalization in tumor tissue. The synergistic anti-tumor effect was abolished after CD8 depletion. CONCLUSIONS: Lenalidomide can enhance the anti-tumor effects of sorafenib in HCC through its immune modulatory effects, and CD8(+) TILs play an important role in the anti-tumor synergism.

Genome analysis of Salinimicrobium sp. 3283s, a deep-sea bacterium isolated from the sediments of South China Sea, China.

Salinimicrobium sp. 3283s is an aerobic, golden-yellow pigment-producing, Flavobacteriaceae bacterium isolated from the sediments at the depth of 1751 m in the South China Sea. In this study, we present the complete genome sequence of strain 3283s, which only have a single circular chromosome comprising 3,702,683 bp with 41.41% G + C content and no circular plasmid. In total, 3257 protein coding genes, 45 tRNA, 9 rRNA, and 13 sRNA genes were obtained. In terms of the function of gene annotation, strain 3283s was more different from Salinimicrobium oceani J15B91, which was isolated from the South China Sea at a similar depth, and more similar to a Mariana Trench-derived strain Salinimicrobium profundisediminis MT39, which was closer in phylogenetic taxonomic status, suggesting that strain 3283s possesses a stronger potential to adapt to the deep-sea environment. Furthermore, the high- pressure simulations also confirmed that strain 3283s can grow in both 30 MPa and 60 MPa hydrostatic pressure environments, and that it grows better in 30 MPa hydrostatic pressure environments than in 60 MPa hydrostatic pressure environments. In addition, we found a large number of genes in strain 3283s that can promote better adaptation of the bacteria to the low oxygen and high hydrostatic pressure (HHP) environment of the deep sea, such as biosynthetic enzymes of antioxidant pigments, genes encoding cytochromes with enhanced affinity for oxygen, proteins for adaptation to HHP, and genes encoding TonB-dependent transporters in the absence of flagella.

Preparation and Performance Evaluation of a New Type of Polyethylene-vinyl Acetate/Polystyrene Microsphere Composite Pour Point Depressant for Waxy Crude Oil.

Polymer/inorganic nanocomposite pour point depressant (PPD) is a research hotspot in the field of waxy crude oil pipelining. However, the inorganic nanoparticles need to be organically modified to improve their organic compatibility, and the inorganic nanoparticles are harmful to crude oil refining. In this work, organic PSMS with an average size of 1.4 µm was first synthesized by dispersion polymerization. Then, a new type of EVA/PSMS composite PPD was prepared by melt blending. The effects of the PSMS, EVA PPD, and composite PPD on the pour point, rheological properties, and wax precipitating properties of a specific waxy crude oil were investigated. It was found that adding 50-200 ppm of PSMS alone slightly improves the crude oil rheology through a spatial hindrance effect, while adding 20 ppm of EVA PPD greatly improves the crude oil rheology by modifying the wax crystal morphology. Compared with EVA PPD, adding 20 ppm composite PPD improves the crude oil rheology further, and the rheological improving ability first enhances and then weakens with increasing the PSMS content in the composite PPD (0-10 wt %). At the PSMS content in the composite PPD 5 wt %, the EVA/PSMS 5% composite PPD makes the wax crystal aggregates more compact, thus showing the strongest rheological improving ability. The EVA molecules could adsorb on the PSMS and form the composite particles, which further regulate the wax crystal morphology and then improve the crude oil rheology further.

Research on different compound combinations of Realgar-Indigo naturalis formula to reverse acute promyelocytic leukemia arsenic resistance by regulating autophagy through mTOR pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: In China, the Chinese patent drug Realgar-Indigo naturalis Formula (RIF) is utilized for the therapy of acute promyelocytic leukemia (APL). Comprising four traditional Chinese herb-Realgar, Indigo naturalis, Salvia miltiorrhiza, and Pseudostellaria heterophylla-it notably includes tetra-arsenic tetra-sulfide, indirubin, tanshinone IIa, and total saponins of Radix Pseudostellariae as its primary active components. Due to its arsenic content, RIF distinctly contributes to the therapy for APL. However, the challenge of arsenic resistance in APL patients complicates the clinical use of arsenic agents. Interestingly, RIF demonstrates a high remission rate in APL patients, suggesting that its efficacy is not significantly compromised by arsenic resistance. Yet, the current state of research on RIF's ability to reverse arsenic resistance remains unclear. AIM OF THE STUDY: To investigate the mechanism of different combinations of the compound of RIF in reversing arsenic resistance in APL. MATERIALS AND METHODS: The present study utilized the arsenic-resistant HL60-PMLA216V-RARα cell line to investigate the effects of various RIF compounds, namely tetra-arsenic tetra-sulfide (A), indirubin (I), tanshinone IIa (T), and total saponins of Radix Pseudostellariae (S). The assessment of cell viability, observation of cell morphology, and evaluation of cell apoptosis were performed. Furthermore, the mitochondrial membrane potential, changes in the levels of PMLA216V-RARα, apoptosis-related factors, and the PI3K/AKT/mTOR pathway were examined, along with autophagy in all experimental groups. Meanwhile, we observed the changes about autophagy after blocking the PI3K or mTOR pathway. RESULTS: Tanshinone IIa, indirubin and total saponins of Radix Pseudostellariae could enhance the effect of tetra-arsenic tetra-sulfide down-regulating PMLA216V-RARα, and the mechanism was suggested to be related to inhibiting mTOR pathway to activate autophagy. CONCLUSIONS: We illustrated that the synergistic effect of different compound combinations of RIF can regulate autophagy through the mTOR pathway, enhance cell apoptosis, and degrade arsenic-resistant PMLA216V-RARα.

Fine-tuning large language models for chemical text mining.

Extracting knowledge from complex and diverse chemical texts is a pivotal task for both experimental and computational chemists. The task is still considered to be extremely challenging due to the complexity of the chemical language and scientific literature. This study explored the power of fine-tuned large language models (LLMs) on five intricate chemical text mining tasks: compound entity recognition, reaction role labelling, metal-organic framework (MOF) synthesis information extraction, nuclear magnetic resonance spectroscopy (NMR) data extraction, and the conversion of reaction paragraphs to action sequences. The fine-tuned LLMs demonstrated impressive performance, significantly reducing the need for repetitive and extensive prompt engineering experiments. For comparison, we guided ChatGPT (GPT-3.5-turbo) and GPT-4 with prompt engineering and fine-tuned GPT-3.5-turbo as well as other open-source LLMs such as Mistral, Llama3, Llama2, T5, and BART. The results showed that the fine-tuned ChatGPT models excelled in all tasks. They achieved exact accuracy levels ranging from 69% to 95% on these tasks with minimal annotated data. They even outperformed those task-adaptive pre-training and fine-tuning models that were based on a significantly larger amount of in-domain data. Notably, fine-tuned Mistral and Llama3 show competitive abilities. Given their versatility, robustness, and low-code capability, leveraging fine-tuned LLMs as flexible and effective toolkits for automated data acquisition could revolutionize chemical knowledge extraction.

Chinese guidelines for integrated diagnosis and treatment of intestinal microecology technologies in tumor application (2024 Edition).

ABSTRACT: Intestinal microecology (IM) is the largest and most important microecological system of the human body. Furthermore, it is the key factor for activating and maintaining the physiological functions of the intestine. Numerous studies have investigated the effects of the gut microbiota on the different tissues and organs of the human body as well as their association with various diseases, and the findings are gradually being translated into clinical practice. The gut microbiota affects the occurrence, progression, treatment response, and toxic side effects of tumors. The deepening of research related to IM and tumors has opened a new chapter in IM research driven by methods and technologies such as second-generation sequencing and bioinformatics. The IM maintains the function of the host immune system and plays a pivotal role in tumor-control drug therapy. Increasing evidence has proven that the efficacy of tumor-control drugs largely depends on the IM balance, and strategies based on the IM technology show promising application prospects in the diagnosis and treatment of tumor. The Tumor and Microecology Professional Committee of the Chinese Anti-cancer Association gathered relevant experts to discuss and propose the "Chinese guidelines for integrated diagnosis and treatment of IM technologies in tumor application (2024 Edition)," which was established based on the research progress of the application of the IM technology in tumor to provide a basis for the standardization of the diagnosis and treatment of the IM technology in the tumor.

Cortactin is a sensitive biomarker relative to the poor prognosis of human hepatocellular carcinoma.

BACKGROUND: Cortactin is an important regulator involved in invasion and migration of hepatocellular carcinoma (HCC). The aim of this study was to elucidate the forecasting role of cortactin in resectable HCCs. METHODS: We compared the invasiveness and motility among liver epithelial cell line and HCC cell lines by using Transwell assay and wound healing assay. We further investigated the CTTN mRNA expression by real-time PCR. Next, 91 HCC and 20 normal liver tissue samples were detected by IHC and real-time PCR. Finally, we analyzed the clinicopathologic features and survival time of the HCC cases. RESULTS: We identified that HepG2, LM3, and SK-Hep-1 had more invasiveness and motility (P <0.05). Compared with liver epithelial cell line, CTTN expression was higher in LM3, HepG2, and MHCC97-L (P <0.01) and lower in SK-Hep-1 (P <0.05). IHC examination showed cortactin expression was closely relative to TNM stage (AJCC/UICC), cancer embolus, and metastasis (P <0.01). Cortactin overexpression indicated a longer survival time of 52 ± 8.62 months and low expression of a shorter survival time of 20 ± 4.95 months (P <0.01). Cortactin examination has more predictive power in patients with Child-Pugh grade A and BCLC stage 0-B. CONCLUSIONS: Overexpression of cortactin is closely associated with poor human HCCs prognosis that caused by cancer embolus and metastasis. Cortactin and CTTN should be used for differentiating varieties of survival for patients after HCC resection.

Preparation and Performance of Multilayer Si-B-C-N/Diamond-like Carbon Gradient Films.

Si-B-C-N/diamond-like carbon (DLC) gradient films with different layers were prepared on a glass substrate by radio frequency magnetron sputtering, and the structure and surface morphology of the resulting films were analyzed by scanning electron microscopy, Raman spectrometry, and X-ray photoelectron spectroscopy. The mechanical and optical properties of the films were studied using a multifunctional material mechanical testing system, UV-Vis spectrophotometer, and micro-Vickers hardness tester. The gradient structure promotes the formation of sp3 bonds and improves the hardness and optical transmittance of the resulting films. Among the prepared films, the single-layer Si-B-C-N/DLC gradient film shows the highest optical transmittance (97%). Film-substrate adherence is strengthened by the introduction of the gradient structure. The best adhesion was obtained with a double-layer Si-B-C-N/DLC gradient film. Suitable anti-wear properties were exhibited in both dry (0.18) and wet (0.07) conditions. In this paper, evaluation of the microstructural, optical, and mechanical properties of the films could provide new insights into improvements in the bonding force of glass-based DLC films and enrich the experimental data of DLC multilayer film systems.

[4D bioprinting technology and its application in cardiovascular tissue engineering].

3D bioprinting technology is a rapidly developing technique that employs bioinks containing biological materials and living cells to construct biomedical products. However, 3D-printed tissues are static, while human tissues are in real-time dynamic states that can change in morphology and performance. To improve the compatibility between in vitro and in vivo environments, an in vitro tissue engineering technique that simulates this dynamic process is required. The concept of 4D printing, which combines "3D printing + time" provides a new approach to achieving this complex technique. 4D printing involves applying one or more smart materials that respond to stimuli, enabling them to change their shape, performance, and function under the corresponding stimulus to meet various needs. This article focuses on the latest research progress and potential application areas of 4D printing technology in the cardiovascular system, providing a theoretical and practical reference for the development of this technology.

Research on the mechanism of prednisone in the treatment of ITP via VIP/PACAP-mediated intestinal immune dysfunction.

RATIONALE: Immune thrombocytopenia (ITP) is thought to be a result of immune dysfunction, which is treated by glucocorticoids such as prednisone. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) have immunomodulatory properties, but their role in intestinal immune control is unclear. The major goal of this study was to look at the effects of prednisone on platelet, VIP, and PACAP levels in ITP mice, as well as the regulatory system that controls intestinal immunity. METHODS: Eighteen BALB/c mice were randomly divided into three groups: blank control group, model control group, and prednisone group, with six mice in each group. The ITP animal model control group and the prednisone group were injected with anti-platelet serum (APS) to replicate the ITP animal model. The prednisone group began prednisone intervention on the 8th day. Platelet count was dynamically measured before APS injection, on the 4th day of injection, on the 1st day of administration, on the 4th day of administration, and at the end of the experiment. After the experiment, the expression of p53 protein in mouse mesenteric lymph node lymphocytes was detected by immunohistochemistry. The changes in lymphocyte apoptosis rate in mouse mesenteric lymph nodes were detected by in situ terminal transferase labeling (TUNEL). The contents of VIP and PACAP in the mouse brain, colon, and serum were detected by enzyme-linked immunosorbent assay (ELISA). The contents of IFN-γ, IL-4, IL-10, IL-17A in the mouse spleen were detected by ELISA. RESULTS: ①Changes of peripheral platelet count: there was no significant difference in platelet count among the three groups before modeling; on the 4th day, the platelet count decreased in the model control group and prednisone group; on the 8th day, the number of platelets in model control group and prednisone group was at the lowest level; on the 12th day, the platelet count in prednisone group recovered significantly; on the 15th day, the platelet count in prednisone group continued to rise. ②Changes of VIP, PACAP: compared with the blank control group, VIP and PACAP in the model control group decreased significantly in the brain, colon, and serum. Compared with the model control group, the levels of VIP and PACAP in the brain, colon, and serum in the prednisone group were increased except for serum PACAP. ③Changes of mesenteric lymphocytes: the expression of p53 protein in the mesenteric lymph nodes of model control group mice was significantly higher than that of blank control group mice. After prednisone intervention, the expression of p53 protein decreased significantly.④Changes of cytokines in spleen: compared with blank control group, IFN- γ, IL-17A increased and IL-4 and IL-10 decreased in model control group. After prednisone intervention, IFN- γ, IL-17A was down-regulated and IL-4 and IL-10 were upregulated. CONCLUSIONS: Prednisone-upregulated VIP and PACAP levels decreased P53 protein expression and apoptosis rate in mesenteric lymph node lymphocytes and affected cytokine expression in ITP model mice. Therefore, we speculate that the regulation of intestinal immune function may be a potential mechanism of prednisone in treating ITP.