Ghrelin alleviates intestinal ischemia-reperfusion injury by activating the GHSR-1α/Sirt1/FOXO1 pathway.

Ischemia-reperfusion (IR) injury is primarily characterized by the restoration of blood flow perfusion and oxygen supply to ischemic tissue and organs, but it paradoxically leads to tissue injury aggravation. IR injury is a challenging pathophysiological process that is difficult to avoid clinically and frequently occurs during organ transplantation, surgery, shock resuscitation, and other processes. The major causes of IR injury include increased levels of free radicals, calcium overload, oxidative stress, and excessive inflammatory response. Ghrelin is a newly discovered brain-intestinal peptide with anti-inflammatory and antiapoptotic effects that improve blood supply. The role and mechanism of ghrelin in intestinal ischemia-reperfusion (IIR) injury remain unclear. We hypothesized that ghrelin could attenuate IIR-induced oxidative stress and apoptosis. To investigate this, we established IIR by using a non-invasive arterial clip to clamp the root of the superior mesenteric artery (SMA) in mice. Ghrelin was injected intraperitoneally at a dose of 50 µg/kg 20 min before IIR surgery, and [D-Lys3]-GHRP-6 was injected intraperitoneally at a dose of 12 nmol/kg 20 min before ghrelin injection. We mimicked the IIR process with hypoxia-reoxygenation (HR) in Caco-2 cells, which are similar to intestinal epithelial cells in structure and biochemistry. Our results showed that ghrelin inhibited IIR/HR-induced oxidative stress and apoptosis by activating GHSR-1α. Moreover, it was found that ghrelin activated the GHSR-1α/Sirt1/FOXO1 signaling pathway. We further inhibited Sirt1 and found that Sirt1 was critical for ghrelin-mediated mitigation of IIR/HR injury. Overall, our data suggest that pretreatment with ghrelin reduces oxidative stress and apoptosis to attenuate IIR/HR injury by binding with GHSR-1α to further activate Sirt1.

Spring irrigation with magnetized water affects soil water-salt distribution, emergence, growth, and photosynthetic characteristics of cotton seedlings in Southern Xinjiang, China.

BACKGROUND: Spring irrigation with freshwater is widely used to reduce soil salinity and increase the soil water content in arid areas. However, this approach requires a huge amount of freshwater, which is problematic given limited freshwater resources. Utilizing brackish water for spring irrigation in combination with magnetized water technology may be a promising alternative strategy. RESULTS: The objective of this study was to evaluate the effects of four spring irrigation methods (freshwater spring irrigation (FS), magnetized freshwater spring irrigation (MFS), brackish water spring irrigation (BS), and magnetized brackish water spring irrigation (MBS)) on soil water and salt distribution, emergence, growth, and photosynthetic characteristics of cotton seedlings. The results showed that for both freshwater and brackish water, magnetized water irrigation can increase the soil water content for improved desalination effect of irrigation water. Additionally, spring irrigation with magnetized water promoted cotton emergence and seedling growth. Compared with FS treatment, cotton finial emergence rate, emergence index, vigor index, plant height, stem diameter, and leaf area index of MFS treatment increased by 6.25, 7.19, 12.98, 15.60, 8.91, and 20.57%, respectively. Compared with BS treatment, cotton finial emergence rate, emergence index, vigor index, plant height, stem diameter, and leaf area index of MBS treatment increased by 27.78, 39.83, 74.79, 26.40, 14.01, and 57.22%, respectively. Interestingly, we found that spring irrigation with magnetized water can increase the chlorophyll content and net photosynthetic rate of cotton seedlings. The rectangular hyperbolic model (RHM), non-rectangular hyperbolic model (NRHM), exponential model (EM), and modified rectangular hyperbolic model (MRHM) were used to fit and compare the cotton light response curve, and MRHM was determined to be the optimal model to fit the data. This model was used to calculate the photosynthetic parameters of cotton. Compared with FS treatment, the net photosynthetic rate (Pnmax), dark respiration rate (Rd), light compensation point (Ic), light saturation point (Isat), and the range of available light intensity (ΔI) of MFS were increased by 5.18, 3.41, 3.18, 2.29 and 2.19%, respectively. Compared with BS treatment, the Pnmax, Rd, Ic, Isat and ΔI of MBS were increased by 26.44, 29.48, 30.05, 5.13, and 2.27%, respectively. CONCLUSION: The results show that spring irrigation with magnetized brackish water may be a feasible method to reduce soil salt and increase soil water content when freshwater resources are insufficient.

Epidemiological change of influenza virus in hospitalized children with acute respiratory tract infection during 2014-2022 in Hubei Province, China.

PURPOSE: Influenza virus (IFV) causes acute respiratory tract infection (ARTI) and leads to high morbidity and mortality annually. This study explored the epidemiological change of IFV after the implementation of the universal two-child policy and evaluated the impact of coronavirus disease 2019 (COVID-19) pandemic on the detection of IFV. METHODS: Hospitalized children under 18 years with ARTI were recruited from Hubei Maternal and Child Healthcare Hospital of Hubei Province from January 2014 to June 2022. The positive rates of IFV were compared among different periods by the implementation of the universal two-child policy and public health measures against COVID-19 pandemic. RESULTS: Among 75,128 hospitalized children with ARTI, the positive rate of IFV was 1.98% (1486/75128, 95% CI 1.88-2.01). Children aged 6-17 years had the highest positive rate of IFV (166/5504, 3.02%, 95% CI 2.58-3.50). The positive rate of IFV dropped to the lowest in 2015, then increased constantly and peaked in 2019. After the universal two-child policy implementation, the positive rate of IFV among all the hospitalized children increased from 0.40% during 2014-2015 to 2.70% during 2017-2019 (RR 6.72, 95% CI 4.94-9.13, P < 0.001), particularly children under one year shown a violent increasing trend from 0.20 to 2.01% (RR 10.26, 95% CI 5.47-19.23, P < 0.001). During the initial outbreak of COVID-19, the positive rate of IFV decreased sharply compared to that before COVID-19 (0.35% vs. 3.37%, RR 0.10, 95% CI 0.04-0.28, P < 0.001), and then rebounded to 0.91%, lower than the level before COVID-19 (RR 0.26, 95% CI 0.20-0.36, P < 0.001). CONCLUSION: IFV epidemiological pattern has changed after the implementation of the universal two-child policy. More attention should be emphasized to comprehend the health benefits generated by COVID-19 restrictions on IFV transmission in future.

The transcription factor NAC102 confers cadmium tolerance by regulating WAKL11 expression and cell wall pectin metabolism in Arabidopsis.

Cadmium (Cd) toxicity severely limits plant growth and development. Moreover, Cd accumulation in vegetables, fruits, and food crops poses health risks to animals and humans. Although the root cell wall has been implicated in Cd stress in plants, whether Cd binding by cell wall polysaccharides contributes to tolerance remains controversial, and the mechanism underlying transcriptional regulation of cell wall polysaccharide biosynthesis in response to Cd stress is unknown. Here, we functionally characterized an Arabidopsis thaliana NAC-type transcription factor, NAC102, revealing its role in Cd stress responses. Cd stress rapidly induced accumulation of NAC102.1, the major transcript encoding functional NAC102, especially in the root apex. Compared to wild type (WT) plants, a nac102 mutant exhibited enhanced Cd sensitivity, whereas NAC102.1-overexpressing plants displayed the opposite phenotype. Furthermore, NAC102 localizes to the nucleus, binds directly to the promoter of WALL-ASSOCIATED KINASE-LIKE PROTEIN11 (WAKL11), and induces transcription, thereby facilitating pectin degradation and decreasing Cd binding by pectin. Moreover, WAKL11 overexpression restored Cd tolerance in nac102 mutants to the WT levels, which was correlated with a lower pectin content and lower levels of pectin-bound Cd. Taken together, our work shows that the NAC102-WAKL11 module regulates cell wall pectin metabolism and Cd binding, thus conferring Cd tolerance in Arabidopsis.

Recycling of SLC38A1 to the plasma membrane by DSCR3 promotes acquired temozolomide resistance in glioblastoma.

PURPOSE: Glioblastoma multiforme (GBM) is a primary brain tumor with devastating prognosis. Although the O6-methylguanine-DNA methyltransferase (MGMT) leads to inherent temozolomide (TMZ) resistance, approximately half of GBMs were sufficient to confer acquired TMZ resistance, which express low levels of MGMT. The purpose of this study was to investigate the underlying mechanisms of the acquired TMZ resistance in MGMT-deficient GBM. METHODS: The function of Down syndrome critical region protein 3 (DSCR3) on MGMT-deficient GBM was investigated in vitro and in an orthotopic brain tumor model in mice. Purification of plasma membrane proteins by membrane-cytoplasmic separation and subsequent label free-based quantitative proteomics were used to identified potential protein partners for DSCR3. Immunofluorescence was performed to show the reverse transport of solute carrier family 38 member 1 (SLC38A1) mediated by DSCR3. RESULTS: DSCR3 is upregulated in MGMT-deficient GBM cells during TMZ treatment. Both DSCR3 and SLC38A1 were highly expressed in recurrent GBM patients. Silencing DSCR3 or SLC38A1 expression can increase TMZ sensitivity in MGMT-deficient GBM cells. Combination of proteomics and in vitro experiments show that DSCR3 directly binds internalized SLC38A1 to mediate its sorting into recycling pathway, which maintains the abundance on plasma membrane and enhances uptake of glutamine in MGMT-deficient GBM cells. CONCLUSIONS: DSCR3 is a crucial regulator of acquired TMZ resistance in MGMT-deficient GBM. The DSCR3-dependent recycling of SLC38A1 maintains its abundance on plasma membrane, leading to tumor progression and acquired TMZ resistance in MGMT-deficient GBM.

Individualized combination therapies based on whole-exome sequencing displayed significant clinical benefits in a glioblastoma patient with secondary osteosarcoma: case report and genetic characterization.

BACKGROUND: The incidence of osteosarcoma as a secondary neoplasm in glioblastoma patient is extremely rare. The genetic characteristic still remains unclear until now. CASE DESCRIPTION: We reported a 47-year-old female patient with multiple intracranial disseminations and infiltrations (splenium of the corpus callosum and lateral ventricular wall) of a rapid progressive glioblastoma underwent occipital craniotomy and total resection of all the enhancing lesions. Whole-exome sequencing and pathological examination revealed glioblastoma, IDH1 wild type, PTEN deficient, TERT mutated, NF1mutated, MGMT unmethylated. After surgery, the patient received combined therapeutic regimen of TTFields (tumor-treating fields) plus pembrolizumab plus temozolomide and TTFields plus everolimus, which displayed significant clinical benefits. During the combined therapeutic course, an extremely rare secondary malignant neoplasm occurred, femur MR and pathological detection of biopsy tissue demonstrated osteosarcoma. The result of whole-exome sequencing revealed 7 germline mutated genes (EPAS1, SETD2, MSH3, BMPR1A, ERCC4, CDH1, AR). Bioinformatic analysis showed the two germline mutations (MSH3 and ERCC4) induced deficiency in the DNA repair machinery, which resulting in the accumulation of mutations and may generate neoantigens contributing to the development of a secondary osteosarcoma in this case. CONCLUSION: Individualized combination therapies based on whole-exome sequencing displayed significant clinical benefits in this case. Germline MSH3 and ERCC4 mutation may induce a secondary osteosarcoma in glioblastoma patients.

Investigating genetic diversity and population phylogeny of five Chongqing local chicken populations autosomal using microsatellites.

The genetic diversity and population structures of five Chongqing local chicken populations were investigated using by 24 microsatellite markers. Results revealed that the mean number of alleles (NA) ranged from 7.08 (Daninghe chicken, DN) to 8.46 (Nanchuan chicken, NC). The highest observed heterozygosity (HO) and expected heterozygosity (HE) were observed in DN (HO = 0.7252; HE = 0.7409) and the lowest HO and HE were observed in XS (Xiushan native chicken [XS], HO = 0.5910 and HE = 0.6697). The inbreeding coefficient (FIS) within population ranged from 0.022 (DN) to 0.119 (XS). Among the 24 microsatellite markers, four loci (MCW0111, MCW0016, ADL0278, and MCW0104) deviated from the Hardy-Weinberg equilibrium in all the studied populations. The results of population polygenetic analysis based on Nei's genetic distance and STRUCTURE software showed that the clustering of the five populations was incomplete consistent with geographical distribution. Moreover, a large number of gene flows were widespread among different populations, suggesting that genetic material exchanges occurred due to human activities and migration which was also verified by PCoA. In summary, this study preliminarily showed that Chongqing local chicken populations had rich genetic diversity and remarkable genetic divergence, but still high risk in conversion. These findings would be useful to the management of conservation strategies and the utilization of local chicken populations in further.

Regulation of fast and slow light characteristics of the add-drop ring-resonator employing an assisted ring.

We demonstrate theoretically and experimentally that the fast and slow light characteristics of the add-drop ring-resonator (ADRR) can be regulated by introducing an assisted ring. This novel geometry is named ring-assisted add-drop ring-resonator (RA-ADRR). When the assisted ring is under-coupled, the fast and slow light characteristics of through and drop ports of the RA-ADRR will be reversed, which is different from the coupled resonator induced transparency (CRIT) studied previously. With the decrease of loss, the dispersion peak (dip) of the two ports will grow up towards the opposite directions and finally the inversion occurs. Meanwhile, we find that by increasing the circumference of the assisted ring, the dispersion of the two ports could be improved proportionally. The experimental results show that the maximum group delays of the through and drop ports are 115 ns and -485 ns, respectively. This novel phenomenon could greatly enhance the sensitivity of slow light interferometers and also has potential applications in optical communication, network, filtering and switching.

A novel rat model of interbody fusion based on anterior lumbar corpectomy and fusion (ALCF).

BACKGROUND: Rats have been widely used as experimental animals when performing fundamental research because they are economical, rapidly reproducing, and heal quickly. While the rat interbody fusion model has been applied in basic studies, existing rat models generally have shortcomings, such as insufficiently simulating clinical surgery. The purpose of this study was to develop a novel rat model of interbody fusion which more closely represents clinical surgery. METHODS: The internal fixation was designed based on physical measurements of the rats' lumbar spine. Then, ten rats divided into two groups (A and B) underwent anterior lumbar corpectomy and fusion of the L5 vertebrae. Groups A and B were sacrificed four and 8 weeks post-surgery, respectively. Micro-CT and histological examination were used to evaluate the model. Fusion rate, bone volume fraction (BV/TV), trabecular bone number (Tb.N), trabecular bone thickness (Tb.Th), and the area ratio of newly formed bone (NB) were calculated for quantitative analysis. RESULTS: Based on the L5 body dimensions of individual rats, 3D-printed titanium cage of the appropriate size were printed. The operations were successfully completed in all ten rats, and X-ray confirmed that internal fixation was good without migration. Micro-CT suggested that fusion rates in group B (100%) were greater than group A (40%, P < 0.05). The BV/TV (B: 42.20 ± 10.50 vs. A: 29.02 ± 3.25, P < 0.05) and Tb.N (B: 4.66 ± 1.23 vs. A: 1.97 ± 0.40, P < 0.05) were greater in group B than A, and the Tb.Th in group B was lower than group A (B: 0.10 ± 0.04 vs. A: 0.15 ± 0.02, P < 0.05). Histomorphometry results demonstrated that the area ratio of NB in group B were greater than group A (B: 35.72 ± 12.80 vs. A: 12.36 ± 16.93, P < 0.05). CONCLUSION: A rat interbody fusion model based on anterior lumbar corpectomy and fusion has successfully been constructed and verified. It could provide a new choice for fundamental research using animal models of spinal fusion.

MicroRNA-9 overexpression suppresses vulnerable atherosclerotic plaque and enhances vascular remodeling through negative regulation of the p38MAPK pathway via OLR1 in acute coronary syndrome.

Acute coronary syndrome (ACS) is characterized by atherosclerotic plaque rupture with a high incidence of recurrent ischemic events. Several microRNAs are found to be aberrantly expressed in atherosclerotic plaques. This study aims to investigate the effects of microRNA-9 (miR-9) on vulnerable atherosclerotic plaque and vascular remodeling in ACS and underlying mechanisms. Microarray-based gene expression profiling was used to identify differentially expressed genes related to ACS and regulatory miRNAs. Oxidized low-density lipoprotein (lectin-like) receptor 1 (OLR1) was identified to be aberrantly activated in ACS and regulated by miR-9. OLR1 was verified as a target gene of miR-9 by bioinformatics prediction and dual luciferase reporter gene assay. The atherosclerotic models were induced in ApoE-/- mice, in which the agomir or antagomir of miR-9, or small interfering RNA (siRNA) against OLR1 were separately introduced. Serum lipid levels and expression of vascular remodeling and inflammatory response-related factors were determined, respectively. On the basis of the obtained results, in the atherosclerosis mice treated with the agomir of miR-9 and siRNA against OLR1, the p38-mitogen-activated protein kinase (p38MAPK) pathway was inhibited; levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, tumor necrosis factor-α, interleukin-6, and vascular endothelial growth factor were reduced, but the high-density lipoprotein cholesterol level was increased, along with decreased vulnerable atherosclerotic plaque area and enhanced vascular remodeling. Taken together, these findings suggested an inhibitory role miR-9 acts in the formation of vulnerable atherosclerotic plaques in ACS mice, along with a promoted vascular remodeling, via a negative feedback regulation of OLR1-mediated p38MAPK pathway.

Autler-Townes splitting and induced transparency windows in a multimode microfiber knot.

In this Letter, Autler-Townes splitting and induced transparency windows are observed in a multimode microfiber knot. The microfiber knot is fabricated using tapered single-mode fiber, with the knot position located at the transition area of the tapered fiber. The spectrum, in analogy to Autler-Townes splitting, derives from the mode splitting of two high-order excited modes, which is theoretically explained by the multimode transfer matrix method. Moreover, without adding resonators, two induced transparency windows are realized with the tunable coupling coefficients and phase difference of excited knot modes. The tunable, easily fabricated, compact, and robust microfiber knot has potential applications in optical sensing, filters, slow light, and optical switching.

Total Syntheses of (-)-Deoxoapodine, (-)-Kopsifoline D, and (-)-Beninine.

The total syntheses of Aspidosperma and Kopsia alkaloids (-)-deoxoapodine, (-)-kopsifoline D, and (-)-beninine are described through a domino deprotection-Michael addition-nucleophilic substitution protocol to assemble the core framework in efficient steps. Corey-Bakshi-Shibata reduction was employed to afford the enantioenriched intermediate for the total syntheses of the aforementioned alkaloids. The chirality was shown to completely transfer to the backbone using Johnson-Claisen rearrangement. The enantioselective total syntheses of (-)-kopsifoline D and (-)-beninine were accomplished for the first time. Our strategy opens up practical avenues for the total synthesis of structurally similar alkaloids.

Acquired temozolomide resistance in MGMT-deficient glioblastoma cells is associated with regulation of DNA repair by DHC2.

The acquisition of temozolomide resistance is a major clinical challenge for glioblastoma treatment. Chemoresistance in glioblastoma is largely attributed to repair of temozolomide-induced DNA lesions by O6-methylguanine-DNA methyltransferase (MGMT). However, some MGMT-deficient glioblastomas are still resistant to temozolomide, and the underlying molecular mechanisms remain unclear. We found that DYNC2H1 (DHC2) was expressed more in MGMT-deficient recurrent glioblastoma specimens and its expression strongly correlated to poor progression-free survival in MGMT promotor methylated glioblastoma patients. Furthermore, silencing DHC2, both in vitro and in vivo, enhanced temozolomide-induced DNA damage and significantly improved the efficiency of temozolomide treatment in MGMT-deficient glioblastoma. Using a combination of subcellular proteomics and in vitro analyses, we showed that DHC2 was involved in nuclear localization of the DNA repair proteins, namely XPC and CBX5, and knockdown of either XPC or CBX5 resulted in increased temozolomide-induced DNA damage. In summary, we identified the nuclear transportation of DNA repair proteins by DHC2 as a critical regulator of acquired temozolomide resistance in MGMT-deficient glioblastoma. Our study offers novel insights for improving therapeutic management of MGMT-deficient glioblastoma.

Quantitative Proteomics Analysis Reveals Nuclear Perturbation in Human Glioma U87 Cells treated with Temozolomide.

Glioblastoma (GBM) is the most malignant and aggressive glioma, which has a very poor prognosis. Temozolomide (TMZ) is still a first-line treatment, but resistance is inevitable even in MGMT-deficient glioblastoma cells. The aims of this study were to comprehend the effect of TMZ on nucleus and the underlying mechanism of acquired TMZ resistance in MGMT-deficient GBM. We show the changes of nuclear proteome in the MGMT-deficient GBM U87 cells treated with TMZ for 1 week. Label-free-based quantitative proteomics were used to investigate nuclear protein abundance change. Subsequently, gene ontology function annotation, KEGG pathway analysis, protein-protein interaction (PPI) network construction analysis of DAPs, and immunofluorescence were applied to validate the quality of proteomics. In total, 457 (455 gene products) significant DAPs were identified, of which 327 were up-regulated and 128 were down-regulated. Bioinformatics analysis uncovered RAD50, MRE11, UBR5, MSH2, MSH6, DDB1, DDB2, RPA1, RBX1, CUL4A, and CUL4B mainly enriched in DNA damage repair related pathway and constituted a protein-protein interaction network. Ribosomal proteins were down-regulated. Cells were in a stress-responsive state, while the entire metabolic level was lowered. SIGNIFICANCE OF THE STUDY: In U87 cell treated with TMZ for 1 week, which resulted in DNA damage, we found various proteins dysregulated in the nucleus. Some proteins related to the DNA damage repair pathway were up-regulated, and there was a strong interaction. We believe this is the potential clues of chemotherapy resistance in tumour cells. These proteins can be used as indicators of tumour resistance screening in the future.

Progress on genome-wide CRISPR/Cas9 screening for functional genes and regulatory elements.

The CRISPR/Cas9 system is a powerful tool which has been extensively used for genome editing in the past few years. Nuclease-dead Cas9 (CRISPR/dCas9), a Cas9 protein mutant without splicing ability, along with loss-of- function (LOF), gain-of-function (GOF), or non-coding genes scanning approaches can reveal genome-scale functional determinants. CRISPR/Cas9 has been widely adopted to decipher disease mechanisms and pinpoint drug targets in the life science field, and also provide novel insights into animal genetics and breeding. In this review, we summarize the research progress in high-throughput CRISPR/Cas9 screening for revealing the functional genes and regulatory elements in the whole genome. We also highlight the applications of CRISPR/Cas9 system in the animal cells, providing a reference for gene editing and other related research in related fields.

Magnetic-field tuning whispering gallery mode based on hollow microbubble resonator with Terfenol-D-fixed.

We propose a method of magnetic-field tuning whispering gallery modes (WGMs) based on a hollow microbubble resonator (HMBR) with Terfenol-D-fixed. WGMs are excited by the evanescent field from a tapered fiber coupling with an HMBR. Both ends of the HMBR are fixed with Terfenol-D and vary with different lengths of the Terfenol-D. The length of the Terfenol-D varies with the external magnetic field for the high magnetostriction coefficient of Terfenol-D. The magnetic field sensitivity of 0.081 pm/mT in the magnetic field range of 0.14 mT-21.8 mT is achieved. The $Q$Q-factor of the HMBR can be regulated up to ${2.07} \times {{10}^4}$2.07×104 with physical stretching HMBR. This work provides a novel tuning whispering gallery mode scheme and a broad application prospect in the fields of optical measurement and precise optical clocks in the future.

Interleukin-33 Predicts Poor Prognosis and Promotes Renal Cell Carcinoma Cell Growth Through its Receptor ST2 and the JNK Signaling Pathway.

BACKGROUND/AIMS: Renal cell carcinoma (RCC) is currently the ninth most common cancer in men. Interleukin (IL)-33 expression has previously been associated with a number of cancers; however, its biological role in RCC is poorly understood. In this study, we sought to elucidate the role of IL-33 in RCC. METHODS: Serum IL-33 levels were measured by ELISA. IL-33 expression in clinical RCC samples was examined by immunocytochemistry. The proliferation and apoptosis rate of RCC were determined by CCK8 and flow cytometry. Mcl1 and Bcl-2 expression were measured by quantitative real-time PCR and western blotting. JNK expression were measured by western blotting and flow cytometry. The in vivo role of IL-33 in RCC tumorigenesis was examined by animal models. RESULTS: We found that increased expression of IL-33 in RCC was associated with tumor-lymph node-metastasis (TNM) stage and inversely correlated with prognosis. IL-33 enhances RCC cell growth in vivo and stimulates RCC cell proliferation and prevents chemotherapy-induced tumor apoptosis in vitro. Furthermore, we demonstrated that IL-33 promotes RCC cell proliferation and chemotherapy resistance via its receptor ST2 and the JNK signaling activation in tumor cells. CONCLUSION: Our findings suggest that targeting IL-33/ST2 and JNK signaling may have potential value in the treatment of RCC.

[Effect of Electroacupuncture on ATP-sensitive Potassium Channel and Protein Kinase mRNA Ex- pression in Myocardial Ischemia Model Rats].

Objective To observe the effect of electroacupuncture (EA) at different acupoints on mRNA expressions of ATP-sensitive potassium channel (Kir6. 1, Kir6. 2) and conjugated protein (SUR2A, SUR2B) and protein kinases (PKA, PKG and PKC132) in myocardial ischemia model rats. Methods Myocardial ischemia model was established in healthy male SD rats via subcutaneously injec- ting ISO (85 mg/kg) multipointedly (medial root of limbs and the back). Then they were randomly divided into 4 groups, i.e., the model group, Neiguan (PC6) group, Lieque (LU7) group, non-acupoint group, 10 in each group. Besides, another 10 healthy rats were recruited as the control group. Corresponding EA was performed at respective acupoints to rats in Neiguan (PC6) group, Lieque (LU7) group, non-acu- point group, with dense-sparse wave, 2 -3 mA, 2 -20 Hz, needle retaining time of 20 min, once per day for 7 successive days. mRNA expression levels of Kir6. 1 and Kir6. 2, SUR2A, SUR2B, PKA, PKG, and PKCß2 in left ventricular myocardium were analyzed by Real-time PCR. Results Compared with the con- trol group, mRNA expressions of each index increased in the model group (P <0. 01). Compared with the model group, mRNA expressions of each index significantly decreased in Neiguan (PC6) group and Lieque (LU7) group (P<0. 01). Compared with Neiguan (PC6) group, mRNA expressions of each index significantly increased in Lieque (LU7) group and non-acupoint group (P <0. 01). Compared with Lieque (LU7) group, mRNA expressions of each index significantly increased in non-acupoint group (P <0. 05). Conclusion EA at Neiguan (PC6) could reverse mRNA expression changes of ATP-sensitive potassium channel (Kir6. 1 and Kir6. 2)and conjugated proteins (SUR2A and SUR2B) and protein kinases (PKA, PKG, and PKCß2).

Ecotoxicity of two organophosphate pesticides chlorpyrifos and dichlorvos on non-targeting cyanobacteria Microcystis wesenbergii.

Organophosphate pesticides (OPs), as a replacement for the organochlorine pesticides, are generally considered non-toxic to plants and algae. Chlorpyrifos and dichlorvos are two OPs used for pest control all over the world. In this study, the dose-response of cyanobacteria Microcystis wesenbergii on OPs exposure and the stimulating effect of OPs with and without phosphorus source were investigated. The results showed that high concentrations of chlorpyrifos and dichlorvos caused significant decrease of chlorophyll a content. The median inhibitory concentrations (EC50) of chlorpyrifos and dichlorvos at 96 h were 15.40 and 261.16 µmol L(-1), respectively. Growth of M. wesenbergii under low concentration of OPs (ranged from 1/10,000 to 1/20 EC50), was increased by 35.85 % (chlorpyrifos) and 41.83 % (dichlorvos) at 120 h, respectively. Correspondingly, the highest enhancement on the maximum quantum yield (F v/F m) was 4.20 % (24 h) and 9.70 % (48 h), respectively. Chlorophyll fluorescence kinetics, known as O-J-I-P transients, showed significant enhancements in the O-J, J-I, and I-P transients under low concentrations of dichlorvos at 144 h, while enhancements of chlorophyll fluorescence kinetics induced by low concentrations of chlorpyrifos were only observed in the J-I transient at 144 h. Significant decreases of chlorophyll content, F v/F m and O-J-I-P transients with OPs as sole phosphorus source were found when they were compared with inorganic phosphate treatments. The results demonstrated an evidently hormetic dose-response of M. wesenbergii to both chlorpyrifos and dichlorvos, where high dose (far beyond environmental concentrations) exposure caused growth inhibition and low dose exposure induced enhancement on physiological processes. The stimulating effect of two OPs on growth of M. wesenbergii was negligible under phosphate limitation.

Heavy metals in wild marine fish from South China Sea: levels, tissue- and species-specific accumulation and potential risk to humans.

Heavy metal pollution in marine fish has become an important worldwide concern, not only because of the threat to fish in general, but also due to human health risks associated with fish consumption. To investigate the occurrence of heavy metals in marine fish species from the South China Sea, 14 fish species were collected along the coastline of Hainan China during the spring of 2012 and examined for species- and tissue-specific accumulation. The median concentrations of Cd, Cr, Cu, Zn, Pb and As in muscle tissue of the examined fish species were not detectable (ND), 2.02, 0.24, 2.64, 0.025, and 1.13 mg kg(-1) wet weight, respectively. Levels of Cu, Zn, Cd and Cr were found to be higher in the liver and gills than in muscle, while Pb was preferentially accumulated in the gills. Differing from other heavy metals, As did not exhibit tissue-specific accumulation. Inter-species differences of heavy metal accumulation were attributed to the different habitat and diet characteristics of marine fish. Human dietary exposure assessment suggested that the amounts of both Cr and As in marine wild fish collected from the sites around Hainan, China were not compliant with the safety standard of less than 79.2 g d(-1) for wild marine fish set by the Joint FAO/WHO Expert Committee on Food Additives. Further research to identify the explicit sources of Cr and As in marine fish from South China Sea should be established.