A low-frequency normal conducting cavity with higher-order mode damping for fourth-generation synchrotron radiation sources.

The utilization of a low-frequency (<200 MHz) RF system in storage facilitates the attainment of ultra-low emittances in synchrotron light sources through on-axis injection. This paper focuses on the development of a low-frequency normal conducting (NC) cavity with higher-order mode (HOM) damping for fourth-generation synchrotron light sources. We propose a novel approach to achieve efficient HOM damping in a NC cavity by optimizing the lowest frequency HOM and implementing a beam-line absorber. Notably, unlike conventional NC cavities, the presence of a large beam tube for the beam-line absorber does not compromise the accelerating performance in a coaxial resonant cavity, enabling effective HOM damping while maintaining a high shunt impedance. Through simulations, the prototype design of a 166.6 MHz HOM-damped cavity demonstrates a fundamental mode impedance of ∼8 MΩ, with longitudinal and transverse HOM impedances below 2.0 and 50 kΩ/m, respectively.

Effects of individual shock wave therapy vs celecoxib on hip pain caused by femoral head necrosis.

BACKGROUND: Celecoxib has been used to treat hip discomfort and functional difficulties associated with osteonecrosis of the femoral head (ONFH), although significant adverse reactions often follow long-term use. Extracorporeal shock wave therapy (ESWT) can delay the progression of ONFH, alleviate the pain and functional limitations it causes, and avoid the adverse effects of celecoxib. AIM: To investigate the effects of individual ESWT, a treatment alternative to the use of celecoxib, in alleviating pain and dysfunction caused by ONFH. METHODS: This was a randomized, controlled, double-blinded, non-inferiority trial. We examined 80 patients for eligibility in this study; 8 patients were excluded based on inclusion and exclusion criteria. A total of 72 subjects with ONFH were randomly assigned to group A (n = 36; celecoxib + alendronate + sham-placebo shock wave) or group B (n = 36; individual focused shock wave [ESWT based on magnetic resonance imaging three-dimensional (MRI-3D) reconstruction] + alendronate). The outcomes were assessed at baseline, at the end of treatment, and at an 8-wk follow-up. The primary outcome measure was treatment efficiency after 2 wk of intervention using the Harris hip score (HHS) (improvement of 10 points or more from the baseline was deemed sufficient). Secondary outcome measures were post-treatment HHS, visual analog scale (VAS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. RESULTS: After treatment, the pain treatment efficiency of group B was greater than that of group A (69% vs 51%; 95%CI: 4.56% to 40.56%), with non-inferiority thresholds of -4.56% and -10%, respectively. Furthermore, the HHS, WOMAC, and VAS scores in group B dramatically improved during the follow-up period as compared to those in group A (P < 0.001). After therapy, the VAS and WOMAC in group A were significantly improved from the 2nd to 8th wk (P < 0.001), although HHS was only significantly altered at the 2 wk point (P < 0.001). On the 1st d and 2nd wk after treatment, HHS and VAS scores were different between groups, with the difference in HHS lasting until week 4. Neither group had severe complications such as skin ulcer infection or lower limb motor-sensory disturbance. CONCLUSION: Individual shock wave therapy (ESWT) based on MRI-3D reconstruction was not inferior to celecoxib in managing hip pain and restrictions associated with ONFH.

Prenylated dihydroflavones from the root barks of Morus alba.

Three new prenylated dihydroflavones, moralbaflavones A-C (1-3), together with four known ones (4a/4b, 5, and 6) were isolated from the root barks of Morus alba L. Their structures including the absolute configurations were determined by the analysis of HRMS, NMR, and ECD data. The neuroprotective properties of these prenylated dihydroflavones were screened at the concentration of 10 µM in the sodium nitroprusside-induced rat pheochromocytoma PC-12 cells, and the results showed moralbaflavone C (3) possessed significant neuroprotective activity, being more potent than the positive control edaravone.

Mulberry Diels-Alder-type adducts: isolation, structure, bioactivity, and synthesis.

Mulberry Diels-Alder-type adducts (MDAAs) are unique phenolic natural products biosynthetically derived from the intermolecular [4 + 2]-cycloaddition of dienophiles (mainly chalcones) and dehydroprenylphenol dienes, which are exclusively distributed in moraceous plants. A total of 166 MDAAs with diverse skeletons have been isolated and identified since 1980. Structurally, the classic MDAAs characterized by the chalcone-skeleton dienophiles can be divided into eight groups (Types A - H), while others with non-chalcone dienophiles or some variations of classic MDAAs are non-classic MDAAs (Type I). These compounds have attracted significant attention of natural products and synthetic chemists due to their complex architectures, remarkable biological activities, and synthetic challenges. The present review provides a comprehensive summary of the structural properties, bioactivities, and syntheses of MDAAs. Cited references were collected between 1980 and 2021 from the SciFinder, Web of Science, and China National Knowledge Internet (CNKI).

Machine Learning-Devised Immune-Related lncRNA Signature Panel Predicts the Prognosis and Immune Landscape in Breast Cancer Novel IRLP Signature in BRCA.

Long noncoding RNAs (lncRNAs) actively participate in breast cancer (BRCA) tumorigenesis via epigenetic mechanisms. Our study identified immune-related lncRNA (irlncRNA) pairs and compiled them into a set of noncoding gene signatures able to stratify subtypes of BRCA associated with variable degrees of survival and immune cell infiltration. A 40 immune-related lncRNA pair (IRLP) signature including 43 irlncRNAs was built, with high sensitivity and specificity for the prediction of survival in different molecular subtypes of BRCA. Results demonstrated that the low-risk group showed a significantly longer survival rate, and this novel IRLP signature was highly associated with survival status, T stage, metastatic disease, and overall stage in BRCA. Immune infiltrating analyses found that the low-risk group has a lower expression level of macrophage M2 and a higher expression level of immunosuppressed biomarkers than the high-risk group. DEirlncRNAs were further proven to be significantly related to the MAPK signaling, Jak-STAT signaling, and ErbB signaling pathways in BRCA. In conclusion, the 40 IRLP signature showed a promising clinical prediction value in the prognosis of different molecular subtypes and immunotherapy response in BRCA, and the underlying mechanism for these IRLPs warrants further investigations.

[Emission of Nitrous Oxide (N2O) from Lake Taihu and the Corresponding Potential Driving Factors].

Nitrous oxide (N2O) is one of the six greenhouse gases stipulated in the Kyoto Protocol. Its greenhouse potential over the past century was 298 times that of CO2, and the concentration of atmospheric N2O has been continuously and rapidly increasing during the past hundred years. Shallow lakes are an important source of atmospheric N2O. In order to explore the temporal and spatial changes and potential driving factors of N2O emissions from eutrophic water, we conducted field observations in February (winter) and August (summer) in Lake Taihu. We used the coefficient of diffusion-headspace bottle method to trace the variability in the N2O concentration[c(N2O)] and efflux[F(N2O)] from surface water bodies and explored the potential driving factors of N2O emissions. The optical measurements of dissolved organic matter (DOM) are an effective approach for tracing the source and composition of dissolved organic carbon (DOC) and dissolved organic nitrogen (DON). The migration and transformation processes of DOM also release a large amount of inorganic nitrogen, which changes the redox potential of the water column and thereby affects N2O emissions. Our results showed that the variability in c(N2O) and F(N2O) in the surface waters of Lake Taihu were strongly affected by water temperature and nutrient levels. The average c(N2O) of the surface waters was (19.7±2.7) nmol·L-1, corresponding to a mean F(N2O) of (41.1±1.8) µmol·(m2·d)-1, and the means of both c(N2O) and F(N2O) were higher in summer than those in winter (t-test, P<0.01). The input and accumulation of DOM could increase the production and emission potential of N2O in water bodies, as supported by both c(N2O) and F(N2O) significantly increasing with increasing level of terrestrial humic-like C1. The integration ratio of peak C to peak T IC:IT of DOM and the spectral slope S275-295 results indicated that there were high inputs of terrestrial DOM in the northwestern inflowing river mouths, concurring with the high production and emission of N2O found there. This suggested that the accumulation and degradation of terrestrial DOM potentially fueled the emission of N2O. Our results showed that water temperature, DOM composition, and nutrient level were all important factors affecting N2O emission from Lake Taihu. Long-term continuous observation can be applied to better evaluate the impact of various environmental factors on the production and emission of N2O in water bodies and to help with providing scientific emission reduction plans.

Homo/Hetero-Dimers of Aromatic Bisabolane Sesquiterpenoids with Neuroprotective Activity from the Fungus Aspergillus versicolor A18 from South China Sea

Chromatographic fractionation of the EtOH extracts of the marine-derived fungus Aspergillus versicolor A18 has led to the isolation of 11 homo/hetero-dimers of aromatic bisabolane sesquiterpenoids including eight diphenyl ether-coupled aromatic bisabolanes (1a/1b and 5−10) and three homodimers (2−4), together with their monomers including three aromatic bisabolanes (11−13) and two diphenyl ethers (14 and 15). Their structures and absolute configurations were elucidated by extensive spectroscopic analysis including HRESIMS, 1D/2D NMR, calculated ECD, and the optical rotatory data. Among the four new compounds, (+/−)-asperbisabol A (1a/1b), asperbisabol B (2), and asperbisabol C (3), the enantiomers 1a and 1b represent an unprecedented skeleton of diphenyl ether-coupled aromatic bisabolane sesquiterpenoids with a spiroketal core moiety. The neuroprotective effects of selected compounds against sodium nitroprusside (SNP)-induced injury were evaluated in PC12 cells by the MTT assay. Five compounds (1a, 6, and 8−10) showed remarkable neuroprotective activities at 10 µM, being more active than the positive control edaravone.

[Emission of Methane from a Key Lake in the Eastern Route of the South-to-North Water Transfer Project and the Corresponding Driving Factors].

Lakes play an important role in the biogeochemical cycling of dissolved organic matter (DOM) and the emission of methane (CH4). We investigated the concentration and effluxes of CH4 and then analyzed the corresponding driving factors in Lake Luoma, a key lake along the South-to-North Water Transfer Project. Our results indicated that Lake Luoma was a hotspot of CH4 emissions with an annual mean concentration and efflux of (0.12±0.09) µmol·L-1 and (21.0±18.5) mmol·(m2·d)-1, respectively. We found higher mean CH4 levels in the wet season than those in the dry season and further higher levels than those in the wet-to-dry transition season. Spatially, the CH4 efflux was higher in the northwest inflowing regions and lower in the southeast outflow regions. The variability in annual CH4 efflux was affected by a combination of water temperature and hydrological conditions. Terrestrial input of dissolved organic carbon (DOC) and chromophoric DOM (CDOM) had fueled the production of CH4 by providing necessary carbon substrates, and four PARAFAC DOM components were identified including a microbial humic-like C1, a tryptophan-like C2, a terrestrial humic-like C3, and a tyrosine-like C4. The CH4 efflux from the lake was significantly promoted by the input and accumulation of terrestrial humic-like components, and Chl-a had no correlation with CH4 efflux, suggesting that algal degradation was not directly fueling the emission of CH4. Lake Luoma had been significantly disturbed by human activities, and terrestrial input of nutrient loading (TN and TP) into the lake not only improved the productivity and trophic level of the water body but also enhanced the production and release of CH4 from the surface water. We concluded that the CH4 emissions in Lake Luoma can be influenced by the combination of environmental factors, CDOM composition, and nutrient level. Long-term observation is needed for better evaluation of the driving factors in fueling the emission of CH4 so as to effectively reduce the emissions of CH4 and other greenhouse gases by taking corresponding countermeasures.

[Source and Optical Dynamics of Chromophoric Dissolved Organic Matter in the Watershed of Lake Qinghai].

Lake Qinghai is the largest lake in China and is of great significance to maintain the ecological security of the Qinghai-Tibet Plateau. Few studies have been carried out to investigate the optical composition and source of chromophoric dissolved organic matter (CDOM) in large lakes on the Qinghai-Tibet Plateau. It is of great significance to study the source and optical dynamics of CDOM in Lake Qinghai watershed for water quality protection and filling in the gaps in the knowledge of CDOM variability in a remote area. Two sampling campaigns in the Lake Qinghai watershed were carried out, and excitation-emission matrices coupled with parallel factor analysis (EEMs-PARAFAC) were used to unravel the optical composition and the sources of CDOM. Our results indicated that the mean dissolved organic carbon (DOC) concentration, a250:a365, and the spectral slope of CDOM absorption S275-295 in the lake were significantly higher than that in the inflow river (P<0.0001, t-test), whereas the mean absorption coefficient of CDOM a350, humification index (HIX), fluorescence peak integration ratio IC:IT, and specific ultraviolet absorbance at 254 nm SUVA254 of CDOM were shown to be lower in the lake than in the inflow river (P<0.0001), indicating that compared with the lake itself, CDOM in the inflow was humic-rich and highly aromatic. Four fluorescent components were obtained using PARAFAC, including a terrestrial human-like component C1, a microbial human-like component C2, a tyrosine-like C3, and a tryptophan-like C4. The mean DOC concentration, S275-295, and a250:a365in the headwater streams of the Lake Qinghai watershed were lower than those in the downstream estuary, indicating that the CDOM abundance increased, and the molecular weight decreased, from the headwaters to the downstream river mouths. The mean of SUVA254, C1, and the first axis of principal component analysis were positively related to terrestrial input (i.e., the PC1 values were significantly higher in rivers than in lakes (P<0.001)), indicating that the aromaticity of CDOM in rivers was higher than that in lakes. Particularly, the contribution of terrestrial humic-like C1 was higher in the Quanji River, Shaliu River, and Khargai River compared with that in other tributaries due to an intensified cultivated land use at the downstream estuary of these rivers.

[Influences of Hydrological Scenarios on the Bioavailability, Fate, and Balance of Chromophoric Dissolved Organic Matter in Lake Poyang].

Lake Poyang has significant differences in hydrological characteristics between the flood and dry seasons. Unraveling the optical composition, bioavailability, fate, and balance of chromophoric dissolved organic matter (CDOM) and organic carbon fluxes in Lake Poyang under different hydrological conditions can help provide advanced schemes on carbon cycling, the transfer and transformation of organic matter, and water resource management of the lake. Three fluorescent components, including a humic-like (C1), a tryptophan-like (C2), and a tyrosine-like (C3) component, were obtained using three-dimensional fluorescence spectroscopy coupled with parallel factor analysis. Prior to and after 28 days of laboratory biodegradation, the means of a254 and the terrestrial humic-like (C1) component in the flood season were both significantly higher than that in the dry season (t-test, P<0.01), indicating that the terrestrial humic-like (C1) component contributed importantly to the CDOM pool. The contribution percentages of protein-like components in the dry season were 81.7% of the summed fluorescent components of CDOM, indicating that there might be discharge of domestic wastewater from areas surrounding the lake in the dry season. The bioavailabilities of the humic-like (C1) component and DOC were 14.0% and 43.2%, respectively, in the dry season. This can be explained by a declined-dilution effect in the lake during the dry rather than in the flood season. We observed no significant difference in the bioavailability of protein-like components under different hydrological conditions. The bioavailability of C1 (i.e.,%ΔC1) showed a decreasing trend from the southern inflowing river mouths to the downstream northern outlet at Hukou in both the flood and dry seasons, indicating that the bioavailability of the C1 decreased following the migration of CDOM in the lake. In the dry season and flood season, Lake Poyang was the source of DOC with fluxes of 14.0×103 t·mon-1 and 1.4×103 t·mon-1, respectively, whereas CDOM fluxes in corresponding periods were the source and weak sink with corresponding fluxes of 9.3×1010 m3·(m·mon)-1 and 1.1×1010 m3·(m·mon)-1, respectively. Therefore, the lake released substantial organic matter to the downstream receiving waters during the dry season, whereas in the flood season, the higher water level in the Yangtze River resulted in a prolonged water residence time of the lake, and a fraction of CDOM was bio-degraded into inorganic nutrients, favoring the metabolisms and the eutrophication process of the lake ecosystem.

[Sources and Optical Dynamics of Chromophoric Dissolved Organic Matter in Different Types of Urban Water Bodies].

In the past few decades, China's rapid industrial activities and urbanization processes have greatly impacted the urban surface water ecosystem. The changes in the quality of urban surface water directly affect the supply and carbon cycling of urban waters. We collected 50 water samples from urban rivers, lakes, and reservoirs in the city of Changchun in June 2020. Three-dimensional fluorescence spectroscopy coupled with parallel factor analysis (EEMs-PARAFAC) was used to unravel the optical characteristics, composition, and sources of chromophoric dissolved organic matter (CDOM). Our results indicated that the mean concentration of DOC is significantly higher in urban rivers than in reservoirs (t-test, P<0.05), and the mean UV absorption coefficient of CDOM a254 of urban rivers is significantly larger than that of park lakes and reservoirs (t-test, P<0.05), indicating that urban rivers have the highest concentration of CDOM. The spectral slope of CDOM absorption S275-295 and the spectral slope ratio SR were shown to be higher in park lakes than in reservoirs, and even higher than in urban rivers (t-test, P<0.001). Three fluorescent components were obtained using PARAFAC, namely terrestrial human-like (C1), microbial human-like (C2) and tryptophan-like (C3) components. The mean fluorescence intensity of C1-C3 was significantly higher in urban rivers than in both the park lakes and reservoirs (t-test, P<0.005), and the mean fluorescence intensity of C1 in the reservoir water body was significantly higher than that of C2 and C3 (t-test, P<0.005), indicating that the discharge of municipal wastewater likely contributes significantly to the CDOM pool of urban rivers in Changchun, and the contribution percentages of highly bio-labile protein-like components to the CDOM pool in these waters are high. Urban wastewater treatment should be strengthened to effectively protect water quality, as well as the economic, environmental, and ecological functions of urban waters in Changchun City.

Knockout of cytochrome P450 1A1 enhances lipopolysaccharide-induced acute lung injury in mice by targeting NF-κB activation.

Acute lung injury (ALI) is accompanied by overactivation of multiple pro-inflammatory factors. Cytochrome P450 1A1 (CYP1A1) has been shown to aggravate lung injury in response to hyperoxia. However, the relationship between CYP1A1 and lipopolysaccharide (LPS)-induced ALI is unknown. In this study, CYP1A1 was shown to be upregulated in mouse lung in response to LPS. Using CYP1A1-deficient (CYP1A1-/-) mice, we found that CYP1A1 knockout enhanced LPS-induced ALI, as evidenced by increased TNF-α, IL-1ß, IL-6, and nitric oxide in lung; these effects were mediated by overactivation of NF-κB and iNOS. Furthermore, we found that aspartate aminotransferase, lactate dehydrogenase, creatine kinase, and creatinine levels were elevated in serum of LPS-induced CYP1A1-/- mice. Altogether, these data provide novel insights into the involvement of CYP1A1 in LPS-induced lung injury.

Cytochrome P450 1A1 enhances inflammatory responses and impedes phagocytosis of bacteria in macrophages during sepsis.

The hydroxylase cytochrome P450 1A1 (CYP1A1) is regulated by the inflammation-limiting aryl hydrocarbon receptor (AhR), but CYP1A1 immune functions remain unclear. We observed CYP1A1 overexpression in peritoneal macrophages (PMs) isolated from mice following LPS or heat-killed Escherichia. coli (E. coli) challenge. CYP1A1 overexpression augmented TNF-α and IL-6 production in RAW264.7 cells (RAW) by enhancing JNK/AP-1 signalling. CYP1A1 overexpression also promoted 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HETE) production in activated RAW, while a 12(S)-HETE antibody attenuated and 12(S)-HETE alone induced inflammatory responses. Macrophages harbouring hydroxylase-deficient CYP1A1 demonstrated reduced 12(S)-HETE generation and LPS-induced TNF-α/IL-6 secretion. CYP1A1 overexpression also impaired phagocytosis of bacteria via decreasing the expression of scavenger receptor A (SR-A) in PMs. Mice injected with CYP1A1-overexpressing PMs were more susceptible to CLP- or E. coli-induced mortality and bacteria invading, while Rhapontigenin, a selective CYP1A1 inhibitor, improved survival and bacteria clearance of mice in sepsis. CYP1A1 and 12(S)-HETE were also elevated in monocytes and plasma of septic patients and positively correlated with SOFA scores. Macrophage CYP1A1 disruption could be a promising strategy for treating sepsis. Video abstract.

Correction to: Cytochrome P450 1A1 enhances inflammatory responses and impedes phagocytosis of bacteria in macrophages during sepsis.

An amendment to this paper has been published and can be accessed via the original article.

Cytochrome P450 1A1 enhances Arginase-1 expression, which reduces LPS-induced mouse peritonitis by targeting JAK1/STAT6.

The polarization of macrophages is critical to inflammation and tissue repair, with unbalanced macrophage polarization associated with critical dysfunctions of the immune system. Cytochrome P450 1A1 (CYP1A1) is a hydroxylase mainly controlled by the inflammation-limiting aryl hydrocarbon receptor (AhR), which plays a critical role in mycoplasma infection, oxidative stress injury, and cancer. Arginase-1 (Arg-1) is a surrogate for polarized alternative macrophages and is important to the production of nitric oxide (NO) by the modulation of arginine. In the present study, we found CYP1A1 to be upregulated in IL-4-stimulated mouse peritoneal macrophages (PMs) and human peripheral blood monocytes. Using CYP1A1-overexpressing RAW264.7 cells (CYP1A1/RAW) we found that CYP1A1 augmented Arg-1 expression by strengthening the activation of the JAK1/STAT6 signaling pathway in macrophages treated with IL-4. 15(S)-HETE, a metabolite of CYP1A1 hydroxylase, was elevated in IL-4-induced CYP1A1/RAW cells. Further, in macrophages, the loss-of-CYP1A1-hydroxylase activity was associated with reduced IL-4-induced Arg-1 expression due to impaired 15(S)-HETE generation. Of importance, CYP1A1 overexpressing macrophages reduced the inflammation associated with LPS-induced peritonitis. Taken together, these findings identified a novel signaling axis, CYP1A1-15(S)-HETE-JAK1-STAT6, that may be a promising target for the proper maintenance of macrophage polarization and may also be a means by which to treat immune-related disease due to macrophage dysfunction.

[Exogenous agmatine inhibits lipopolysaccharide-induced activation and dysfunction of human umbilical vein endothelial cells].

OBJECTIVE: To investigate whether exogenous agmatine inhibits lipopolysaccharide (LPS)-induced activation and dysfunction of human umbilical vein endothelial cells (HUVECs) by modulating nuclear factor-κB (NF-κB) and MAPK signal pathways and the production of reactive oxygen species (ROS). METHODS: Cultured HUVECs were treated with agmatine at the optimized concentration of 1.0 mmolγL, LPS (10 µgγmL), and LPS + agmatine, with or without pretreatment with the inhibitors of NF-κB (PDTC), p38 (SB203580), and ERK (PD98059) for 1 h. The levels of soluble vascular cell adhesion molecule 1 (VCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin and monocyte chemoattractant protein 1 (MCP-1) in the supernatant were determined using ELISA, and their mRNA expressions, along with heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO-1), were assessed using real-time PCR. ROS production in the cells was determined using 2, 7-dichlorofluoresce in diacetate (DCFH-DA) as the fluorescence probe. The protein expressions of VCAM-1, ICAM-1, p65, phospho-p65 (p-p65), IκBα, p-IκBα, ERK, p-ERK, p38, p-p38, JNK, and p-JNK were detected using Western blotting. RESULTS: LPS stimulation for 6 and 24 h significantly increased the levels of sVCAM-1, sICAM-1, sE-selectin and MCP-1 in the supernatant, intracellular ROS production, and the mRNA expressions of these molecules (P<0.05). Intervention with 1 mmolγL agmatine, similar with pretreatment with p38, ERK and NF-κB inhibitors, obviously inhibited such effects of LPS in HUVECs (P<0.05). Agmatine significantly up-regulated the mRNA expression of HO-1 (P<0.05), inhibited LPS-induced phosphorylation of p38, ERK, nuclear p65 and cytoplasmic IκBα, and up-regulated the protein expression of cytoplasmic IκBα. CONCLUSION: Agmatine inhibits LPS-induced activation and dysfunction of HUVECs by modulating NF-κB and MAPK signal pathways to down-regulate the expressions of adhesion molecules and chemokines and by up-regulating the expression of HO-1 to reduce ROS production.

[Mechanism of Platycarya strobilacea Sieb. et Zucc extract-induced methuosis in human nasopharyngeal carcinoma CNE1 and CNE2 cells].

OBJECTIVE: To study the effect of Platycarya strobilacea Sieb. et Zucc (PSZ) extract on methuosis of human nasopharyngeal carcinoma CNE1 and CNE2 cells and explore the underlying mechanism. METHODS: CNE1 and CNE2 cells were treated with 1 mg/mL PSZ extract and the expressions of Rac1 mRNA and Rac1 protein were detected using RT-qPCR and Western blotting, respectively. Results CNE1 and CNE2 cells showed obvious morphological changes typical of methuosis following treatment with PSZ extract characterized by cell merging, accumulation of large cytoplasmic vacuoles, and membrane rupture without obvious changes in the nuclei. PSZ treatment resulted in up-regulated Rac1 mRNA and Rac1 protein expressions in the cells. Application of EHT 1864 obviously blocked the effect of PSZ extract in inducing methuosis in CNE1 and CNE2 cells. CONCLUSION: PSZ extract can induce methuosis in CNE1 and CNE2 cells by inducing the overexpression of Rac1.

Evodiamine Inhibits Zymosan-Induced Inflammation In Vitro and In Vivo: Inactivation of NF-κB by Inhibiting IκBα Phosphorylation.

Evodiamine (EVO), an important alkaloidal component extracted from the fruit of Evodiae fructus, has been known to possess anti-tumor, anti-inflammatory, anti-oxidative, and other therapeutic capabilities. In the present study, the effects of EVO on zymosan-induced inflammation and its underlying mechanism were investigated both in vitro and in vivo. Our results showed that EVO effectively suppressed both protein and mRNA expression of interleukin-1ß, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in vitro. Zymosan-induced DNA-binding activity of nuclear factor-kappa B (NF-κB) was attenuated by EVO, which was achieved through inhibitory effects on the phosphorylation of inhibitory κB α and p65 nuclear translocation, but there was very little association with mitogen-activated protein kinase activation. In vivo, treatment with EVO markedly decreased TNF-α and IL-6 levels in plasma. EVO also repressed inflammatory cytokine expression and ameliorated the abnormal state in both lung and intestine tissues by inactivation of NF-κB. Furthermore, EVO significantly reduced the mortality caused by zymosan. In summary, these results suggested that EVO could effectively suppress inflammatory responses in vitro and in vivo, and may be a potential therapeutic agent against inflammatory disorders.

[Clinical Efficacy of Sorafenib Combined with Low Dose Cytarabine for Treating Patients with FLT3+ Relapsed and Refractory Acute Myeloid Leukemia].

OBJECTIVE: To study the efficacy and safety of sorafenib combined with low dose cytarabine for treating patients with FLT3(+) relapsed and refractory acute myeloid leukemia (FLT3(+) RR-AML). METHODS: Seven patients with FLT3(+) RR-AML were treated with sorafenib and low dose cytarabine. The curative rate and adverse effects were observed in these patients. RESULTS: Out of 7 RR-AML patients after treatment, 5 patients achieved complete remission (CR), 2 patients achieved partial remission (PR), and the overall response rate (ORR) after one course of therapy was 100%. No severe bleeding, nausea, vomiting and other side effects were found in these patients. CONCLUSION: Sorafenib combined with low dose cytarabine can effectively induce the remission of FLT3(+) RR-AML patients, and is worth for further clinical trails to verify its safty and efficiency.