Clinical significance of downregulated NISCH expression in skin cutaneous melanoma: Modulation of tumor cell invasion, migration, and EMT via PAK1 inhibition.

OBJECTIVE: This study aimed to investigate the expression and functional role of NISCH in skin cutaneous melanoma (SKCM), exploring its association with clinical characteristics and its potential impact on human skin melanoma cell behavior. METHODS: The research assessed differential NISCH expression in SKCM tissues using the GEPIA (Gene Expression Profiling Interactive Analysis) database and validated these findings through immunohistochemical staining of 45 clinical samples. To affirm NISCH expression at the cellular level, three human skin melanoma cell lines (RPMI-7951, A375, MEL-5), and the human normal skin cell line HEMa underwent quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. Transwell experiments evaluated the migration and invasion capabilities of RPMI-7951 and A375 cells post-transduction with NISCH or PAK1 lentiviral activation particles. Additionally, qRT-PCR analysis of epithelial-mesenchymal transition (EMT)-related gene expression (Vimentin, E-cadherin, N-cadherin) was conducted in A375 and RPMI-7951 cells. RESULTS: SKCM tissues exhibited significantly reduced NISCH expression compared to normal tissues. Immunohistochemical analysis revealed predominant nuclear localization of NISCH in melanoma cells, with reduced expression significantly correlating with sex, advanced stage, and lymph node metastasis. Melanoma cell lines displayed lower NISCH expression levels compared to normal skin cells. Functional experiments showcased that NISCH overexpression suppressed p-PAK1/PAK1, while PAK1 upregulation notably increased melanoma cell migration, invasion, and induced EMT. Remarkably, NISCH overexpression counteracted PAK1-induced effects on EMT, migration, and invasion in melanoma cells. CONCLUSION: NISCH may significantly influence the aggressive behavior of SKCM cells via the PAK1 pathway, making it a potential therapeutic target for managing melanoma metastasis.

Inhibiting IL11RA to mitigate hepatic metastasis in skin cutaneous melanoma: Comprehensive insights from in vitro and in vivo investigations.

OBJECTIVE: This study aimed to investigate the role of Interleukin-11 receptor alpha (IL11RA) in skin cutaneous melanoma (SKCM) metastasis to the liver. METHODS: Human SKCM cell lines (A375, A375-MA2, SK-MEL-28, RPMI-7951) and primary dermal fibroblasts (HDFa) were utilized to assess IL11RA expression. IL11RA siRNA was transfected into RPMI-7951 and A375-MA2 cells for Wound healing and Transwell invasion assays. Il11ra knockout (KO) mice and wild-type (WT) mice were injected with B16-F10 cells into the spleen to evaluate hepatic melanoma metastasis. Correlation between IL11RA and MMP family genes was explored using online databases, including LinkedOmics, TIMER (Tumor Immune Estimation Resource), and GEPIA (Gene Expression Profiling Interactive Analysis). RT-qPCR and Western blotting were performed for expression analysis of Mmp2 and Mmp9 in liver tissues of mice. The impact of IL11RA on the STAT3 pathway was investigated in vitro and in vivo. RESULTS: Elevated expression of IL11RA was observed in SKCM cell lines compared to normal cells. IL11RA downregulation significantly inhibited migratory and invasive capabilities of A375-MA2 and RPMI-7951 in vitro. Il11ra gene knockout in mice demonstrated a substantial reduction in hepatic melanoma metastasis. Correlation analyses revealed associations between IL11RA and MMP2/MMP8. Il11ra gene knockout significantly decreased Mmp2 expression while increasing Mmp8 in liver tissues. IL11RA correlated positively with STAT3, and its inhibition led to a suppressed STAT3 pathway in SKCM cells and mouse liver tissue. CONCLUSION: IL11RA plays a crucial role in SKCM metastasis, affecting migratory and invasive abilities. Targeting IL11RA may offer a promising avenue for therapeutic interventions in cutaneous melanoma progression.

Enantioselective vinylogous aldol/lactonization cascade reaction between ß,γ-unsaturated amides and trifluoromethyl ketones: facile access to chiral trifluoromethyl dihydropyranones.

An efficient asymmetric vinylogous aldol/lactonization cascade reaction between ß,γ-unsaturated amides and trifluoromethyl ketones has been developed. Using a chiral cyclohexanediamine-based tertiary amine-thiourea catalyst, optically active trifluoromethyl dihydropyranones have been constructed in moderate-to-excellent yields (up to 99%) with excellent stereoselectivities (96-> 99.5% ee).

Knockdown of miR-660 protects nucleus pulposus cells from TNF-a-induced apoptosis by targeting serum amyloid A1.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a well-known cause of lower back pain, which is induced by multiple factors including increased apoptosis and decreased survival of nucleus pulposus cells. In this study, we evaluate the effect and potential mechanism of miR-660 on the nucleus pulposus cells apoptosis induced by TNF-α. METHODS: First, we collected tissue of nucleus pulposus from IVDD and healthy controls. General characteristic of the IVDD and healthy control was also collected. And, we also collected nucleus pulposus cells that stimulated by TNF-α or control. miRNA microarray was performed to identify the differentially expressed miRNAs. Apoptosis rate and miR-660 relative expression was measured after stimulated with different concentration of TNF-α to identify the optimal concentration of TNF-α. Second, we successfully constructed antigomiR-660 to block the miR-660 expression in nucleus pulposus cells and then stimulated with TNF-α (100 ng/ml, 12 h). The apoptosis rates and relative protein expression were then measured again. The target association between miR-660 and SAA1 was confirmed by dual-luciferase reporter. RESULTS: There was no significant difference between the age (IVDD: 39 ± 10 years, healthy controls: 36 ± 7 years), BMI and sex between IVDD and healthy controls. Microarray analysis found that miR-660 was significantly up-regulated in IVDD and TNF-α treated groups, which was further identified by PCR. We found that the rate of apoptosis and miR-660 expression increased with TNF-α concentration increased. Finally, TNF-a with 100 ng/ml was used for further experiment. Compared with TNF-α group, TNF-α + antigomiR-660 could significantly down-regulated the apoptosis rate and relative protein (c-Caspase3 and c-Caspase7). Dual-luciferase reporter revealed that miR-660 could directly binding to the SAA1 at 80-87 sites. Compared with TNF-α alone group, TNF-α + antigomiR-660 significantly up-regulated the SAA1 expression (P < 0.05). CONCLUSION: These results indicated that knockdown of miR-660 protected the nucleus pulposus from apoptosis that induced TNF-α via up-regulation of SAA1. Further studies should focus on the role of miR-660 in protecting IVDD in vivo.

Regioselective and Enantioselective Cu(II)-Catalyzed 1,4-Conjugate Addition of Diethylzinc Reagent to Nitrodienes.

The regioselective and enantioselective Cu(II)-catalyzed 1,4-conjugate addition of diethylzinc reagent to nitrodienes is described. With 0.25 mol % of Cu(OAc)2 and chiral amidophosphine ligand L3, the 1,4-addition products were produced with a complete regioselectivity, high yields (81-98%), and excellent enantioselectivities (87-97% ee) in a short reaction time.

Identifying and assessing human activity impacts on groundwater quality through hydrogeochemical anomalies and NO3-, NH4+, and COD contamination: a case study of the Liujiang River Basin, Hebei Province, P.R. China.

In the face of rapid economic development and increasing human activity, the deterioration of groundwater quality has seriously affected the safety of the groundwater supply in eastern China. Identifying and assessing the impact of human activities is key to finding solutions to this problem. This study is an effort to scientifically and systematically identify and assess the influence of human activities on groundwater based on irregularities in hydrochemical properties and water contamination, which are considered to directly result from anthropogenic activity. The combination of the hydrochemical anomaly identification (HAI) and the contaminant identification (CI) was proposed to identify the influence of human activities on groundwater quality. And the degree of abnormality was quantified by the background threshold value. The principal component analysis (PCA) and land use map were used to verify the reliability of the identification result. The final result show that the strong influence areas mainly distributed in the south of the basin and the affected indicators contained the major elements and NO3-, NH4+, COD. Impacts from anthropogenic activities can be divided into two types: mine drainage that disrupts natural water-rock interaction processes, agricultural cultivation, and sewage emissions that contribute to nitrate pollution.

[Effect of Biochar on Adsorption Behavior of Nonylphenol onto Loess Soil in Northwest China].

In the present study, nonylphenol (NP) was selected as the target pollutant to investigate the effect of biochar produced from wheat residue at different temperatures on loess soil based on the batch experiments. The research basically included adsorption kinetic, thermodynamic and some influencing factors such as biochar with different pyrolysis temperature, particle size and pH value. The results showed that the adsorption reaction of NP onto loess soil without biochar was 10 h during fast reaction, and after the addition of biochar into loess soil, the fast reaction time of NP adsorption was shortened. Meanwhile, in the fast stage the adsorption reaction of NP onto loess soil with biochar was significantly higher than loess soil without biochar, while the difference of adsorption capacity was small at different carbonization temperatures. The adsorption reaction of NP onto loess soil by adding biochar could be well described by the pseudo-second-order kinetics model and reached equilibrium in 16 h. The kinetic data showed that the adsorption of NP accorded well with the Freundlich isotherm model. The saturated adsorption capacity was improved as temperature increased with or without biochar. Thermodynamic parameter analysis indicated Gibbs free energy ΔGθ<0, entropy ΔHθ>0 and enthalpy ΔSθ>0, demonstrating it was a spontaneous, endothermic and chaos-increasing adsorption process. At the same temperature, the adsorption capacity of NP in loess soils increased dramatically with the increase of carbonization temperature. The smaller particle size of the loess with the addition of biochar, the better the adsorption of NP. When the pH value was 4 to 7, the adsorption capacity of NP onto loess soil by adding biochar showed an increasing trend; in the pH range of 7 to 10, the adsorption saturation capacity decreased with the increase of pH value. Therefore, the adsorption of NP on loess with the addition of biochar had the best adsorption effect in the neutral range. Acid and alkalinity were not conducive to the adsorption of NP.

[Adsorption Behavior of p-hydroxy Biphenyl onto Sediment of the Yellow River in Lanzhou].

In order to study the adsorption behavior of organic pollutants in sediment of the Yellow River in Lanzhou, p-hydroxy biphenyl (PHB) was selected as the typical organic pollutants to understand the adsorption kinetics and thermodynamics of PHB onto sediment of the Yellow River in Lanzhou based on the batch experiments. Meanwhile, the effects of systemic temperature, such as the particle size, the initial concentration of PHB, pH value, and the ionic strength, were also investigated for the adsorption of PHB onto sediment of the Yellow River. The results indicated that the adsorption kinetics of PHB onto sediment of the Yellow River could be better described by Pseudo-second-order model, and the boundary layer and intraparticle diffusion were both involved in the adsorption kinetic process. The adsorption thermodynamics of PHB onto sediment of the Yellow River were fitted well with the Langmuir model(R2>0.974), which was a single molecular layer adsorption process. The average adsorption free energy E ranged from 0.913 to 1.00 kJ·mol-1 when the systemic temperatures increased from 25℃ to 45℃, suggesting a physical adsorption. Thermodynamic parameter analysis indicated that Gibbs free energy (ΔGθ) and Entropy (ΔHθ) were less than zero, but Enthalpy (ΔSθ) was more than zero in the adsorption process, which tended to prove the spontaneous nature of the adsorption process, the endothermic nature of the adsorption process and the increased randomness at the sediment surface. Furthermore, the smaller the particle size, the greater the adsorption capacity of the PHB. The adsorption capacity was increased with the increase of the initial concentration of PHB. When the pH value in a range of 4.23 to 7.00, the adsorption capacity of PHB showed a slow decreasing trend, while the decreasing was sharp when pH value was greater than 7.00, and the adsorption capacity was almost zero when pH value was about 10.3. With the increase of ionic strength, the adsorption amount of PHB was also increased, but when the ionic strength increased to a certain value, due to the competitive adsorption, the adsorption of PHB onto sediments would be inhibited, resulting in decreased amount of adsorption.

[Serotype distribution of non-polio enterovirus in patients with acute flaccid paralysis during 2011-2012 in Hebei Province, China].

This study aims to investigate the serotype distribution of non-polio enterovirus (NPEV) isolated from patients with acute flaccid paralysis (AFP) during 2011-2012 in Hebei Province, China and to analyze the relationship between these viruses and AFP. NPEV strains were isolated from the stool specimens from AFP cases in Hebei using human rhabdomyosarcoma cells (RD) and the mouse cell line expressing the gene for the human cellular receptor for poliovirus (L20B) according to the WHO requirements. The nucleotide sequence of VP1 region was determined, and the serotypes of NPEV were identified by molecular typing. The results showed that among the 82 strains of NPEV isolated from the AFP cases during 2011-2012, 42 isolates (55.3%) were identified as human enterovirus A (HEV-A), which were classified into 4 serotypes, 34 (44.7%) as human enterovirus B (HEV-B), which were classified into 13 serotypes, 2 as adenovirus, and 4 were untyped; human enteroviruses C and D were not found in these cases. Enterovirus A71 (EV-A71) was the main type of HEV-A, accounting for 85.7% of all HEV-A strains. HEV-A, especially EV-A71, was predominant among the NPEV strains isolated from AFP patients during 2011-2012 in Hebei Province.

Germinable soil seed banks and the restoration potential of abandoned cropland on the Chinese hilly-gullied loess plateau.

Poor vegetation cover is generally considered to be a major factor causing soil erosion on the Loess Plateau in China. It has been argued that tree planting restoration is ineffective, and natural re-vegetation is an alternative ecological solution for restoring abandoned cropland and controlling soil erosion. The aims of this study were to investigate the characteristics of soil seed banks and to assess the natural restoration potential of abandoned cropland in the hilly-gullied Loess Plateau. The soil seed bank was identified by the germination method with the soil samples, which were collected at four sampling times (April, August, and October 2005 and August 2006) from 12 plots abandoned 3-30 years prior to sampling. The seed bank densities of all of the samples in the 0-10 cm soil layer varied from 1,067 ± 225 to 14,967 ± 1,606 seeds m(-2). Fifty-one species (24 annual and 27 perennial species) belonging to 18 families were identified, and 39% of these species belonged to the families Compositae and Gramineae. The pioneer species Artemisia scoparia dominated the seed bank, with an average seed density of 3,722 seeds m(-2), and accounted for 74.4% of the seeds in the bank. The local dominant species (such as Lespedeza davurica, Artemisia gmelinii, Bothriochloa ischaemun and Stipa bungeana) of the later succession stages also existed at densities varying from 17 to 1, 383 seeds m(-2). The combination of soil seed bank characteristics, reproductive traits of the species, the specific landscape conditions indicates that the potential to restoring the abandoned croplands in the hilly-gullied Loess Plateau via natural re-vegetation could be substantial.

Chiral resolutions of (9-anthryl)methoxyacetic acid and (9-anthryl)hydroxyacetic acid by capillary electrophoresis.

The resolutions of (9-anthryl)methoxyacetic acid (9AMAA) and (9-anthryl)hydroxyacetic acid (9AHAA) were performed by capillary electrophoresis using hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as a chiral selector. Various factors affecting migration time and resolutions of these compounds were investigated with a run voltage of 20 kV, column temperature 20 degrees C and 20 mM Tris-H(3)PO(4) buffer (pH 6.5) containing 5 mM HP-beta-CD for 9AMAA, or 10 mM HP-beta-CD for 9AHAA, (+/-)-9AMAA and (+/-)-9AHAA were successfully separated at Rs 3.27 and 1.92, respectively.