Knockdown of ribosome RNA processing protein 15 suppresses migration of hepatocellular carcinoma through inhibiting PATZ1-associated LAMC2/FAK pathway.

BACKGROUND: Ribosomal RNA processing protein 15 (RRP15) has been found to regulate the progression of hepatocellular carcinoma (HCC). Nevertheless, the extent to which it contributes to the spread of HCC cells remains uncertain. Thus, the objective of this research was to assess the biological function of RRP15 in the migration of HCC. METHODS: The expression of RRP15 in HCC tissue microarray (TMA), tumor tissues and cell lines were determined. In vitro, the effects of RRP15 knockdown on the migration, invasion and adhesion ability of HCC cells were assessed by wound healing assay, transwell and adhesion assay, respectively. The effect of RRP15 knockdown on HCC migration was also evaluated in vivo in a mouse model. RESULTS: Bioinformatics analysis showed that high expression of RRP15 was significantly associated with low survival rate of HCC. The expression level of RRP15 was strikingly upregulated in HCC tissues and cell lines compared with the corresponding controls, and TMA data also indicated that RRP15 was a pivotal prognostic factor for HCC. RRP15 knockdown in HCC cells reduced epithelial-to-mesenchymal transition (EMT) and inhibited migration in vitro and in vivo, independent of P53 expression. Mechanistically, blockade of RRP15 reduced the protein level of the transcription factor POZ/BTB and AT hook containing zinc finger 1 (PATZ1), resulting in decreased expression of the downstream genes encoding laminin 5 subunits, LAMC2 and LAMB3, eventually suppressing the integrin ß4 (ITGB4)/focal adhesion kinase (FAK)/nuclear factor κB kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. CONCLUSIONS: RRP15 promotes HCC migration by activating the LAMC2/ITGB4/FAK pathway, providing a new target for future HCC treatment.

Swertiamarin ameliorates diet-induced obesity by promoting adipose tissue browning and oxidative metabolism in preexisting obese mice.

Obesity is a risk factor for many metabolic diseases. Efficient therapeutic strategies are urgently needed. Swertiamarin (STM) prevents obesity and the associated insulin resistance and inflammation. However, the therapeutic effects of STM on preexisting obesity remain unclear. Therefore, in this study we aim to investigate the effects of STM on energy expenditure and fat browning in mice with preexisting obesity. C57BL/6J mice are fed with a high-fat diet (HFD) for 8 weeks to induce obesity and then gavaged (or not) with STM for 10 weeks. The whole-body energy metabolism of mice is examined by indirect calorimetry. The results show that after 10 weeks of treatment, STM markedly prevents HFD-induced weight gain, chronic inflammation, insulin resistance, and hepatic steatosis. STM promotes oxygen consumption and energy expenditure. The level of uncoupling protein 1 is enhanced in the brown and white adipose tissues of STM-treated mice. STM increases the phosphorylation of AMP-activated protein kinase and the expressions of genes involved in fat oxidation, reducing fat deposition in skeletal muscles. Meanwhile, STM does not affect the intestinal microbiotic composition. Overall, STM supplementation may serve as a potential therapy for obesity.

Ligand-Controlled NiH-Catalyzed Regiodivergent Chain-Walking Hydroalkylation of Alkenes.

A NiH-catalyzed migratory hydroalkylation of alkenyl amines with predictable and switchable regioselectivity is reported. By utilizing a ligand-controlled, directing group-assisted strategy, various alkyl units are site-selectively installed at inert sp3 C-H sites far away from the original C=C bonds. A range of structurally diverse α- and ß-branched protected amines are conveniently synthesized via stabilization of 5- and 6-membered nickelacycles respectively. This method exhibits broad scope and high functional group tolerance, and can be applied to late-stage modification of medicinally relevant molecules.

The discovery of quinoline derivatives, as NF-κB inducing kinase (NIK) inhibitors with anti-inflammatory effects in vitro, low toxicities against T cell growth.

NIK is a critical regulatory protein of the non-classical NF-kB pathway, and its dysregulated activation has been proved to be one of the pathogenic factors in a variety of autoimmune diseases and inflammatory diseases. Nevertheless, its corresponding development of inhibitors faces many obstacles, including the lack of structure types of known inhibitors, immature activity evaluation methods of compounds in vitro. In this study, a series of quinoline derivatives were obtained through rational design and chemical synthesis. Among them, the representative compounds 17c and 24c have excellent inhibitory activities on LPS-induced macrophage (J774) nitric oxide release and anti-Con A-stimulated primary T cell proliferation. This evaluation method has good universality and overcomes the obstacles mentioned above, which are faced by the current inhibitor research to a certain extent. Besides, the compound's toxicity against the growth of T cells under non-stress conditions was evaluated, for the first time, as an indicator for the investigation to avoid potential safety risks. Pharmacokinetic properties evaluation of the less toxic compound 24c confirmed its good metabolic behavior (especially oral properties, F% = 21.7%), and subsequent development value.

Micaryolanes A and B, Two New Caryolane-Type Sesquiterpenoids from Marine Streptomyces sp. AH25.

Caryolanes, known as ß-caryophyllene alcohols, are widely occurring sesquiterpenes in plants. From the cultures of marine Streptomyces sp. AH25, two new caryolane sesquiterpenes, micaryolanes A and B (1 and 2), together with caryolan-1,9ß-diol (3) were isolated. Their structures were elucidated by extensive analyses of HR-MS and NMR spectroscopic data. The absolute configurations were assigned via the CD data of the in situ formed [Rh2 (OCOCF3 )4 ] complex and supported by comparison of experimental and calculated specific rotation values. Compounds 1-3 exhibited no activities against Hep3B or MG-63 cell lines or against Gram-positive and Gram-negative bacteria. The results not only enriched the caryolane family, but also proved bacteria as a productive source of terpene metabolites.

ZnGaNO Photocatalyst Particles Prepared from Methane-Based Nitridation Using Zn/Ga/CO3 LDH as Precursor.

Methane-based nitridation was employed to produce wurtzite zinc-gallium oxynitride (ZnGaNO) photocatalyst particles using Zn/Ga/CO3 layered double hydroxides (LDHs) as precursor. Introduction of methane to nitridation would promote the formation of Zn-O bonding and suppress shallow acceptor complexes such as V(Zn)-Ga(Zn) and Ga-Oi in ZnGaNO particles. On the other hand, high flow rate of methane would induce breaking of Ga-N bonding and enhance surface deposition of metallic Ga atoms. After loading with Rh and RuO2, ZnGaNO particles had free electron density in an order of S50 > S20 > S90 > S0, which correlated well with their photocatalytic performance upon visible-light irradiation. The best performance of the loaded S50 was ascribed to the relatively flat surface band bending of the particle. Methane-based nitridation of Zn/Ga/CO3 LDHs would provide a new route to tune the surface chemistry of ZnGaNO and enhance the photocatalytic performance to its full potential.

Rhodium(iii)-catalyzed ortho-alkenylation using a cyclic N-phosphoryl ketimine as the directing group.

A novel cyclic N-phosphoryl ketimine structure can efficiently react with olefins as useful directing groups to construct a myriad of phosphate scaffolds via rhodium(iii)-catalyzed ortho-alkenylation. This method provides a probability that the coupling products could be used as a building block to access more complex organic phosphorus compounds.

One-Pot Synthesis of Polysubstituted Spirofluorene-Indene via Ru(II)-Catalyzed [3 + 2] Annulation and Intramolecular Friedel-Crafts Cyclization.

Ru(II)-catalyzed one-pot synthesis of polysubstituted spirofluorene-indenes via [3 + 2] annulation and then intramolecular Friedel-Crafts alkylation has been achieved. The simple method provides a broad scope of aryl ketones and internal alkynes, achieving PAHs skeletons in moderate to good yields.

Rhodium(III)-catalyzed three-component reaction of imines, alkynes, and aldehydes through C-H activation.

An efficient rhodium(III)-catalyzed tandem three-component reaction of imines, alkynes and aldehydes through CH activation has been developed. High stereo- and regioselectivity, as well as good yields were obtained in most cases. The simple and atom-economical approach offers a broad scope of substrates, providing polycyclic skeletons with potential biological properties.

Highly efficient selective hydrogenation of adiponitrile to hexamethylene diamine over barium and melamine formaldehyde resin-modified nickel-cobalt-based zeolitic imidazolate framework-derived catalyst.

In the present study, the catalyst modified with alkaline oxide can enhance the selectivity to primary amines. However, the addition of alkaline oxide inevitably reduces catalytic activity. In this study, NiCo-NC@BaO-MFC catalyst derived from zeolitic imidazolate framework-67, Ba(CH3COO)2, and melamine formaldehyde (MF) resin was prepared and used for the hydrogenation of adiponitrile (ADN) to hexamethylene diamine (HDMA). The carbon layer obtained from the MF resin effectively prevents the interaction between barium (Ba) and the active center, thus improving target product selectivity without decreasing catalytic activity. The results of the density functional theory (DFT) calculation and characterization indicated that the effect of synergy between nickel (Ni) and cobalt (Co) bimetals induces an electron density growth on the Ni surface, bringing the d-band center toward the Fermi surface. Meanwhile, the high electron density of the active center compensates for the electron-deficient state of the carbon atom in -CN, thus improving the catalytic activity. Furthermore, it was found that the introduction of Ba promotes the formation of nucleophilic hydrogen anions, which facilitates the hydrogenation of 6-aminohexylimine (AHIM) to HDMA and inhibits the intramolecular condensation of AHIM, hence improving the selectivity to HDMA. The NiCo-NC@BaO-MFC catalyst gives 98.6 % ADN conversion and 97.2 % selectivity to HDMA in an alkali-free system.

Cenicriviroc Suppresses and Reverses Steatohepatitis by Regulating Macrophage Infiltration and M2 Polarization in Mice.

The inhibition of hepatic macrophage and Kupfer cell recruitment and activation is a potential strategy for treating insulin resistance and nonalcoholic steatohepatitis (NASH). Cenicriviroc (CVC), a dual C-C chemokine receptor 2 (CCR2) and CCR5 antagonist, has shown antifibrotic activity in murine models of NASH and has been evaluated in clinical trials on patients with NASH. This study investigated the effects of CVC on macrophage infiltration and polarization in a lipotoxic model of NASH. C57BL/6 mice were fed a high-cholesterol, high-fat (CL) diet or a CL diet containing 0.015% CVC (CL + CVC) for 12 weeks. Macrophage recruitment and activation were assayed by immunohistochemistry and flow cytometry. CVC supplementation attenuated excessive hepatic lipid accumulation and peroxidation and alleviated glucose intolerance and hyperinsulinemia in the mice that were fed the CL diet. Flow cytometry analysis revealed that compared with the CL group, mice fed the CL + CVC diet had fewer M1-like macrophages, more M2-like macrophages, and fewer T cell counts, indicating that CVC caused an M2-dominant shift of macrophages in the liver. Similarly, CVC decreased lipopolysaccharide-stimulated M1-like macrophage activation, whereas it increased interleukin-4-induced M2-type macrophage polarization in vitro. In addition, CVC attenuated hepatic fibrosis by repressing hepatic stellate cell activation. Lastly, CVC reversed insulin resistance as well as steatosis, inflammation, and fibrosis of the liver in mice with pre-existing NASH. In conclusion, CVC prevented and reversed hepatic steatosis, insulin resistance, inflammation, and fibrogenesis in the liver of NASH mice via M2 macrophage polarization.

High Urine Albumin-to-Creatinine Ratio is Associated with Increased Arterial Stiffness in Diabetes: A Chinese Cross-Sectional Study.

Purpose: Elevated urine albumin-to-creatinine ratio (UACR) is an established risk factor for microvascular disease in the general population. However, it is unclear whether UACR is associated with arterial stiffness in diabetes. We aimed to assess the relationship between UACR levels and the risk of arterial stiffness in patients with diabetes. Methods: From July 2021 to February 2023, a total of 1039 participants were assessed for the risk of arterial stiffness, which was evaluated by brachial-ankle pulse wave velocity (baPWV). The value of UACR≥30 mg/g was defined as high UACR. The UACR level had an abnormal distribution and was log2-transformed for analyses to reduce skewness and volatility. High baPWV was evaluated as categorical variables divided by the highest quartile of the values by sex. The relationship between UACR and arterial stiffness was analyzed by linear curve fitting analyses. Multiple logistic regression models were used to analyze the crude and adjusted odds ratio (OR) of UACR for high baPWV with 95% confidence interval (CI). In addition to applying non-adjusted and multivariate-adjusted models, interaction and stratified analyses were also carried out. Results: The baPWV level was significantly higher in the high UACR group compared with that in the normal UACR group (1861.84 ± 439.12 cm/s vs 1723.13 ± 399.63 cm/s, p<0.001). Adjusted smoothed plots suggested that there are linear relationships between log2-transformed UACR and high baPWV, and Spearman correlation coefficient was 0.226 (0.176-0.276, p<0.001). The OR (95% CI) between log2-transformed UACR and high baPWV were 1.26 (1.19-1.33, p<0.001), and 1.16 (1.08-1.25, p<0.001) respectively in diabetic patients before and after adjusting for potential confounders. Conclusion: The elevated UACR was associated with arterial stiffness in Chinese patients with diabetes.

1. The mean baPWV level was significantly higher in the high UACR group compared with that in the normal UACR group.2. The sex-specific hierarchical analysis revealed that baPWV levels and the incidence of high baPWV were significantly elevated with increased UACR.3. Curvilinear relationships between log2-transformed UACR and the risk of high baPWV.4. Positive association between UACR and high baPWV in patients with diabetes.

N-(Pyrazin-2-yl)-1,8-naphthyridin-2-amine.

There are two independent mol-ecules in the asymmetric unit of the title compound, C12H9N5, in which the C-N(amine)-C angles differ slightly [129.63 (11) and 132.02 (11)°]. In each independent mol-ecule, an intra-molecular C-H⋯N hydrogen bond stabilizes the mol-ecular structure, forming an S(6) ring motif. The independent mol-ecules are linked via an N-H⋯N hydrogen bond. Further N-H⋯N and C-H⋯N hydrogen bonds connect the mol-ecules into chains along c axis. Pairs of C-H⋯π inter-actions between the chains lead to sheets parallel to the b axis. These are linked by π-π inter-actions between the naphthyridine and pyrazine rings [centroid-centroid separations of 3.553 (8) Å] into a three-dimensional supra-molecular network.

Case report: 177Lu DOTA-TATE: a new scheme for the treatment of prostate neuroendocrine cancer.

Background: Most instances of small cell carcinoma originate from the lungs, while the gastrointestinal tract serves as a secondary site. Only a minuscule proportion of cases manifest within the urogenital system. Prostate small cell carcinoma (SCCP) represents an exceedingly uncommon pathological subtype within the realm of prostate cancer, displaying significant rarity in clinical settings. This scarcity has resulted in a paucity of adequate foundational and clinical research for SCCP treatment. While investigations have unveiled a certain therapeutic efficacy of radiotherapy and chemotherapy for SCCP, clinical practice has revealed suboptimal treatment outcomes. We hereby present a case report detailing the utilization of 177Lu-DOTA-TATE in the treatment of SCCP, aiming to investigate the therapeutic efficacy of 177Lu-DOTA-TATE for SCCP. Case presentation: A male patient in his 80s presented with elevated prostate-specific antigen (PSA) levels and underwent a biopsy that revealed prostate adenocarcinoma. The patient received CAB (bicalutamide + goserelin) therapy. One year later, disease progression was detected, and a second biopsy confirmed the presence of prostate small cell carcinoma. Following the diagnosis of prostate small cell carcinoma, the patient underwent two cycles of 177Lu-DOTA-TATE treatment. Subsequent to the treatment, the original lesions showed shrinkage, metastatic lesions disappeared, and there was significant improvement, approaching complete remission. Conclusion: SCCP exhibits a high degree of malignancy and aggressive invasiveness, currently lacking effective therapeutic modalities. The treatment course of this patient serves as compelling evidence for the efficacy of 177Lu-DOTA-TATE in managing SCCP, thereby opening new avenues for future SCCP treatments.

(E)-2-[(2-Amino-phen-yl)imino-meth-yl]-4,6-di-tert-butyl-phenol.

In the title compound, C(21)H(28)N(2)O, the dihedral angle between the rings is 35.2 (2)°. A weak intra-molecular O-H⋯N hydrogen bond is observed between the O-H H atom and the imine N atom. In the crystal, mol-ecules are linked by additional inter-molecular N-H⋯O hydrogen bonding, resulting in a wave-like chain along the b-axis direction.

Construction of Digital Economy Trade Security Evaluation System Based on Computational Intelligence.

The upgrading of the digital economy (DE) is crucial to building an intelligent society. The rapid development of computational intelligence in recent years has also brought vitality to the development of the DE. However, with the deepening of international trade, the issue of trade security has become more and more prominent. Therefore, this study aimed to construct a DE trade security evaluation system. For computational intelligence, this study proposes a support vector machine based on improved particle swarm optimization. Such an algorithm can play a key role in the construction of an evaluation system. It is built for the evaluation system. This study selects five indicators of market competitiveness, trade control, trade dependence, market concentration, and trade legal system evaluation. The experimental results of this study prove that the evaluation system proposed in this study is effective. In its test for some countries in the world, the UK trade security index was the highest at 0.582, while China was relatively low at 0.492.

The Propulsion Path of Synergy and Linkage Based on Artificial Intelligence and Digital Economy.

From conception to birth, artificial intelligence inherited the power of human reproduction, such as creativity, self-improvement and language use, etc. These abilities cannot be exercised in other places. The purpose of this paper is to explore the path of collaborative promotion based on artificial intelligence and digital economy. First, it outlines the scattered use of data by individuals at the two application levels of the digital economy and the systematic use of data by enterprises on large organizations. In this study, artificial intelligence and digital economy are introduced into the ability of project information sharing in the field of the enterprise project, and then their important role in improving the performance of enterprise project management is analyzed. Secondly, try to use interviews, scale analysis and logical subtraction to formulate the measurement standards of the digital environment and project information publishing ability, and provide basic data for follow-up research. The experimental results show that 54% of middle-level personnel said that the synergy between enterprise artificial intelligence and digital economy is very good, and they have a positive attitude toward exploring new ways to promote digital economy integration in the field of artificial intelligence.

Effects of Incontro, Alleanza, Responsabilita, Autonomia Intervention Model Combined with Orem Self-Care Model and the Use of Smart Wearable Devices on Perceived Stress and Self-Efficacy in Patients after Total Hip Arthroplasty.

Objective: To explore the effects of Incontro, Alleanza, Responsabilita, Autonomia (IARA) combined with Orem self-care model and the use of smart wearable devices on perceived stress and self-efficacy in patients after total hip arthroplasty (THA). Methods: A total of 60 patients after THA in our hospital were enrolled. Patients were randomly divided into control group (IARA intervention model combined with Orem self-care model) and study group (intelligent wearable device combined conference-IARA and Orem self-care model). Harris hip function score, Western Ontario and McMaster Universities Arthritis Index (WOMAC) score, functional independence measure (FIM) score, social support level, perceived stress, and self-efficacy were compared between the two groups. Results: Harris hip function score, WOMAC score, FIM score, and the level of social support of the study group were higher compared with the control group after operation (P < 0.05). Additionally, the perceptual pressure in the study group was lower compared with the control group after intervention (P < 0.05). The self-efficacy of the two groups was compared, and the self-efficacy of the study group was higher than that of the control group at 4, 6, 8, and 12 weeks after the intervention, and the difference was statistically significant (P < 0.05). Conclusion: Patients after THA utilize an intelligent wearable device combined with IARA model and Orem self-care model, which can effectively reduce awareness pressure, improve self-efficacy, and facilitate the improvement of the hip fracture.

Suppression of obesity by melatonin through increasing energy expenditure and accelerating lipolysis in mice fed a high-fat diet.

BACKGROUNDS/OBJECTIVES: Melatonin promotes brown adipose tissue (BAT) activity, leading to body mass reduction and energy expenditure. However, the mechanisms governing these beneficial effects are not well-established. This study aimed to assess the effects of (1) melatonin on BAT and energy metabolism, and (2) fibroblast growth factor 21 (FGF21) in BAT-mediated thermogenesis. METHODS: Male C57BL/6 J mice received a high-fat diet (HFD) or normal chow, accompanied by intraperitoneal injection of 20 mg/kg melatonin for 12 weeks. FGF21-/- mice consumed an HFD with or without melatonin for 8 weeks. RESULTS: Melatonin attenuated weight gain, insulin resistance, adipocyte hypertrophy, inflammation, and hepatic steatosis induced by the HFD and increased energy expenditure. Furthermore, melatonin improved cold tolerance by increasing BAT uncoupling protein 1 (UCP1) expression and producing heat. Notably, melatonin resulted in a shift in energy metabolism favouring the utilization of fat, and it increased FGF21 in circulating and metabolic tissues and skeletal muscle phosphorylation of AMP-activated protein kinase. However, melatonin did not protect against obesity, insulin resistance, and energy expenditure in HFD-fed FGF21-/- mice. CONCLUSIONS: Melatonin suppressed obesity and insulin resistance resulting from the HFD by enhancing BAT activity and energy expenditure, and these effects were dependent on FGF21.

Patterns of multimorbidity in community health centres in Shanghai, China: a retrospective, cross-sectional study based on outpatient data from 2014 to 2018.

OBJECTIVE: Caring for patients with multimorbidity is an important part of primary care. It has become increasingly relevant that understanding the spectrum of multimorbidity will help general practitioners (GPs) acquire working knowledge and improve management skills. However, there was little research on characteristics of multimorbidity in primary care in China. This study aimed to identify the spectrum of frequency, proportion and ranking of multimorbidity patterns in adult patients seen at community health centres (CHCs) in Shanghai, China. DESIGN AND SETTING: This was an observational, retrospective, cross-sectional study analysis of outpatient data of 244 CHCs in Shanghai, China. PARTICIPANTS: Adult patients with chronic disease who visited Shanghai CHCs during 2014-2018 were selected from Shanghai CHC electronic medical records database using the International Classification of Diseases 10th Revision codes matched to the Second Version of International Classification of Primary Care codes. PRIMARY AND SECONDARY OUTCOME MEASURES: A number of adult patients with chronic disease were counted. Then frequency, proportion and rank of disease patterns of multimorbidity were analysed. RESULTS: Analysis of 301 651 158 electronic health records of 5 909 280 adult patients (54.2% females) found the multimorbidity proportion to be 81.2%. The prevalence of multimorbidity increased with age, which climbed from 43.7% among those aged 19-34 to 94.9% among those more than 80 years of age. The proportion of multimorbidity was higher in females (83.2%) than males (79.7%). Vascular and metabolic diseases were the most frequent diseases for patients over 45 years old. CONCLUSIONS: Multimorbidity has brought huge challenges to primary care practice in Shanghai. The Shanghai government should strengthen its support for the multitargeted prevention of chronic diseases and the improvement of GPs' management capabilities.