Therapeutic value of lymph node dissection for Siewert type II and III adenocarcinoma: meta-analysis.

BACKGROUND: Adenocarcinoma of the oesophagogastric junction presents an increasing incidence. Surgical resection with lymphadenectomy is the only curative treatment modality at the present time, but the optimal extent of lymphadenectomy is debatable. The aim of the present meta-analysis was to estimate the therapeutic value of each nodal station. METHODS: Studies reporting the therapeutic value index of each nodal station in Siewert types II/III oesophagogastric junction (EGJ) were searched in PubMed, Web of Science and Embase up to October 2022. This index was calculated by multiplication of metastatic incidence and 5-year overall survival rate at each nodal station. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Prevalence Studies. Pooled metastatic incidence and therapeutic value index were calculated using RevMan 5.4. RESULTS: Twelve studies involving 3513 patients were included. Nodes No. 3, 1, 7 and 2 were routinely dissected and achieved a high (≥10) or moderate (5-10) therapeutic value index in decreasing order, due to their high metastatic incidence and favourable survival rate. The index was relatively low (2-5) in suprapancreatic nodes No. 9, 11p and 8a. The index for nodes No. 4d and 10 was relatively low in Siewert type Ⅲ EGJ but very low (<2) in type Ⅱ. The index was very low for nodes No. 5, 6, 11d and 12a, due to their low metastatic incidence and poor survival if positive. Para-aortic, parahiatal and mediastinal nodes were dissected only in highly selected cases. Dissection of the lower mediastinal nodes, especially No. 110, could improve survival rates in type Ⅱ EGJ. CONCLUSION: These data could help assess the optimal extent of lymphadenectomy for EGJ. Nodes No. 1, 2, 3, 7, 8a, 9 and 11p need routine dissection in both Siewert types Ⅱ/Ⅲ EGJ; nodes around the lower oesophagus (especially No. 110) in Siewert type Ⅱ EGJ and nodes No. 4d and 10 in Siewert type Ⅲ EGJ might be considered for dissection.

Detecting the steerability through an optimized steering criterion in two-photon systems.

The steerability of a quantum state can be detected by steering inequalities. The linear steering inequalities show that more steerable states can be discovered with the increase of measurements. In order to detect more steerable states in two-photon systems, we first theoretically derive an optimized steering criterion based on infinity measurements for an arbitrary two-qubit state. The steering criterion is only determined by the spin correlation matrix of the state, and do not require infinity measurements. Then, we prepared the Werner-like states in two-photon systems, and measure their spin correlation matrices. Finally, we apply three steering criteria, which include our steering criterion, the three-measurement steering criterion and the geometric Bell-like inequality, to distinguish the steerability of these states. The results show that our steering criterion can detect the most steerable states under the same experimental conditions. Thus, our work provides a valuable reference for detecting the steerability of quantum states.

Flame-retardant effect of tannic acid-based intumescent fire-retardant applied on flammable natural rubber.

Tannic acid (TA) is a natural phenolic compound abundant in plants. Its characteristics of low combustion and good absorption make it useful in the flame retardant field. On this basis, a new expansive flame retardant system (ACT) composed of ammonium polyphosphate (APP)/TA functional clay (CT) was used to study the synergistic flame retardancy and smoke suppression of natural rubber (NR). Because of their unique flame retardancy and better mechanical properties compared with the traditional expansive flame retardant system (IFR), new flame retardants have attracted much attention in various fields. The results of the cone calorimeter showed that the ACT system can significantly influence the decomposition behavior of NR and form a highly graphitized and phosphorous carbon layer to protect the composite material, thus a synergistic effect is produced on the flame retardancy and smoke suppression performance of the composite material. In addition, within the effective additive quality range of the ACT system, TC can give the NR composite excellent mechanical properties.

A Ferroptosis-Related Gene Signature for Predicting Survival and Immunotherapy Effect in Renal Cancer.

Background: Most recently, no efficient prognostic indictor is present for kidney cancer. Thus, we aimed to build and validate a new prognostic gene signature for renal cancer patients using the Cancer Genomic Atlas (TCGA). Methods: A "time-dependent receiver operating characteristic (tROC)" curve was generated, and a log-rank test was performed to assess the performance of the biomarker in training and validation. A "ferroptosis-related gene signature" was developed. In different training and validations sets, tROC and log-rank test were used to validate the biomarker's performance. Results: In the training set with a P value less than 0.01 and the validation set, the "gene signature" was significantly correlated with survival. Eventually, it was found that the ferroptosis-related gene signature was directly correlated with immune score and the score of tumor mutation, suggesting its role in predicting response to immunotherapy. Conclusion: We developed and validated a "ferroptosis-related gene signature" that can be sued for patients with kidney cancer. It can also assist in facilitating the plan for treatment and risk stratification.

Glucocorticoid Receptor-Dependent Astrocytes Mediate Stress Vulnerability.

BACKGROUND: Major depressive disorder is a devastating psychiatric illness that affects approximately 17% of the population worldwide. Astrocyte dysfunction has been implicated in its pathophysiology. Traumatic experiences and stress contribute to the onset of major depressive disorder, but how astrocytes respond to stress is poorly understood. METHODS: Using Western blotting analysis, we identified that stress vulnerability was associated with reduced astrocytic glucocorticoid receptor (GR) expression in mouse models of depression. We further investigated the functions of astrocytic GRs in regulating depression and the underlying mechanisms by using a combination of behavioral studies, fiber photometry, biochemical experiments, and RNA sequencing methods. RESULTS: GRs in astrocytes were more sensitive to stress than those in neurons. GR absence in astrocytes induced depressive-like behaviors, whereas restoring astrocytic GR expression in the medial prefrontal cortex prevented the depressive-like phenotype. Furthermore, we found that GRs in the medial prefrontal cortex affected astrocytic Ca2+ activity and dynamic ATP (adenosine 5'-triphosphate) release in response to stress. RNA sequencing of astrocytes isolated from GR deletion mice identified the PI3K-Akt (phosphoinositide 3-kinase-Akt) signaling pathway, which was required for astrocytic GR-mediated ATP release. CONCLUSIONS: These findings reveal that astrocytic GRs play an important role in stress response and that reduced astrocytic GR expression in the stressed subject decreases ATP release to mediate stress vulnerability.

Dynamic observation on collateral circulation construction of patient with vertebral artery restenosis after stenting: case report.

Purpose/aim of the study: Posterior circulation stroke (PCS) accounts for 20% of ischemic stroke, and vertebrobasilar stenosis is an important cause of PCS. Notably, not all patients with artery stenosis progress to ischemic stroke, and one of the important reason is that collateral circulation construction plays important protection role in this process.Clinical presentation: Here, we present the case of a 71-year-old male who presented with lightheadedness and three episodes of loss of consciousness after bilateral subclavian artery stenting. Digital subtraction angiography (DSA) demonstrated severe stenosis of the left vertebral artery, and the bilateral subclavian artery was kept open. The patient was then given the left vertebral artery stenting in an effort to resolve the vascular stenosis. As expected, he achieved a complete remission after stenting. However, 6 months later the patient suffered from loss of consciousness again. Repeat DSA confirmed restenosis of the left vertebral artery, and revealed a collateral flow to the left vertebral artery which fed by external carotid collateral branches. Then DSA was performed after 12 months, and another collateral circulation involving thyrocervical trunk was also found supplying flow to the left vertebral artery. In this process, the frequency of loss of consciousness gradually decreased as the collateral circulation construction. Conclusion: Through this case, we observe the whole process of the collateral circulation construction. Moreover, this case serves as a testament to the variability and complexity of vertebrobasilar arteriopathies, suggesting promotion of collateral flow offers the opportunity for outcome improvement.

Estimating quantum steering and Bell nonlocality through quantum entanglement in two-photon systems.

Quantum entanglement, quantum steering and Bell nonlocality, as significant quantum resources in the field of quantum information science, can achieve variously valuable quantum information tasks. Among of them, quantum entanglement and Bell nonlocality are the weakest and strongest nonlocal correlations, respectively. One can capture the quantum steering and Bell nonlocality via violating steering inequality and Bell inequality, respectively. In general, the detections of quantum steering and Bell nonlocality are strictly harder than entanglement detection. Here, based on steering inequality test and quantum state tomography, we attain various nonlocal correlations and experimentally demonstrate that the estimations of quantum steering and Bell nonlocality can be realized according to the quantum entanglement of the prepared two-photon test states. The estimated efficiency of quantum steering is stronger than the one of Bell nonlocality in this scenario, i.e., more steerable two-photon test states can be verified through quantum entanglement. In addition, quantum steering and Bell nonlocality are bounded by the corresponding upper and lower bounds, and these bounds cannot be punctured by all prepared two-photon states in experiment. These results are conducive to understand the relations among these nonlocal correlations.

[Stability of Soil Aggregates at Different Altitudes in Qinling Mountains and Its Coupling Relationship with Soil Enzyme Activities].

To explore changes in soil aggregate stability along an elevation gradient, and its regulating factors, soil samples were taken from the 0-10 cm surface layer at 3 different elevations on Taibai Mountain. We measured and analyzed the distribution of soil aggregates, physical and chemical properties, microbial biomass, and extracellular enzymes. The results showed that: ① the soil aggregates from the 3 elevations had mean weight diameters (MWD) of 2.17 mm, 1.83 mm, and 1.82 mm (increasing elevation), and geometric mean diameters (GMD) of 1.66 mm, 1.39 mm, and 1.32 mm, respectively. ② The change in soil aggregate stability along an elevation gradient was regulated by extracellular enzymes in the soil, in particular, the LAP in soil meso-aggregate and the BG in soil micro-aggregate. ③ Microorganisms can alleviate the N limitation at high elevations by adjusting the relative production of extracellular enzymes and altering nutrient utilization efficiency, which also changes soil aggregate stability along an elevation gradient. The results of this study have important scientific significance for soil quality evaluation and ecological environment protection in Taibai Mountain.

Recessive/dominant model: Alternative choice in case-control-based genome-wide association studies.

An additive genetic model is usually employed in case-control-based genome-wide association studies. The model usually encodes "AA", "Aa" and "aa" ("a" represents the minor allele) as three different numbers, implying the contribution of genotype "Aa" to the phenotype is different from "AA" and "aa". From the perspective of biological phenomena, the coding is reasonable since the phenotypes of lives are not "black and white". A case-control based study, however, has only two phenotypes, case and control, which means that the phenotypes are "black and white". It suggests that a recessive/dominant model may be an alternative to the additive model. In order to investigate whether the alternative is feasible, we conducted comparative experiments on several models used in those studies through chi-square test and logistic regression. Our simulation experiments demonstrate that a recessive model is better than the additive model. The area under the curve of the former has increased by 5% compared with the latter, the discrimination of identifying risk single nucleotide polymorphisms has been improved by 61%, and the precision has also reached 1.10 times that of the latter. Furthermore, the real data experiments show that the precision and area under the curve of the former are 16% and 20% higher than the latter respectively, and the area under the curve of dominant model of the former is 13% higher than the latter. The results indicate a recessive/dominant model may be an alternative to the additive model and suggest a new route for case-control-based studies.

Impaired calcium signaling in astrocytes modulates autism spectrum disorder-like behaviors in mice.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder. The mechanisms underlying ASD are unclear. Astrocyte alterations are noted in ASD patients and animal models. However, whether astrocyte dysfunction is causal or consequential to ASD-like phenotypes in mice is unresolved. Type 2 inositol 1,4,5-trisphosphate 6 receptors (IP3R2)-mediated Ca2+ release from intracellular Ca2+ stores results in the activation of astrocytes. Mutations of the IP3R2 gene are associated with ASD. Here, we show that both IP3R2-null mutant mice and astrocyte-specific IP3R2 conditional knockout mice display ASD-like behaviors, such as atypical social interaction and repetitive behavior. Furthermore, we show that astrocyte-derived ATP modulates ASD-like behavior through the P2X2 receptors in the prefrontal cortex and possibly through GABAergic synaptic transmission. These findings identify astrocyte-derived ATP as a potential molecular player in the pathophysiology of ASD.

Transcriptome analysis identifies the differentially expressed genes related to the stemness of limbal stem cells in mice.

Limbal stem cells (LSCs) reside in the basal layer of limbal epithelial cells (LECs). They are crucial for maintenance of corneal epithelium homeostasis and corneal wound healing. Their stemness is determined by their gene expression pattern. Despite of several positive identifiers have been reported, the unique biomarker for LSCs still remain elusive. Differentially expressed genes (DEGs) between stem cells and differentiated cells affect the fate of stem cells via specific signaling pathway. In order to understand the DEGs in the LSCs, RNA-seq was firstly conducted using a mouse model. A total of 1907 up-regulated DEGs and 395 down-regulated DEGs were identified in the limbus (L) compared to central cornea (CC) and conjunctiva (Cj). Reliability of the expression of genes from RNA-seq analysis was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence staining. The expression pattern of putative biomarkers was considered to be age-related. In up-regulated DEGs GO analysis, 570 gene ontology (GO) terms were significantly enriched. Five groups of genes related with biological processes from these significantly enriched GO terms comprised ionic transport, regulation of tissue development, muscle contraction, visual perception, and cell adhesion, which were clustered as a weighted similar network. Whereas, in down-regulated DEGs GO analysis, 61 GO terms were significantly enriched and only one group of ATP biosynthesis and metabolic process were clustered. Furthermore, we identified 55 signaling pathways by the Kyoto Encyclopedia of Genes and Genomes (KEGG) database based on up-regulated genes and 14 KEGG pathways based on down-regulated genes. In this study, we provide a landscape of the expression of putative LSCs biomarkers and stemness-related signaling pathways in a mouse model. Our findings could aid in the identification of LSC niche factors that may be related to the stemness of the LSCs.

Improved NLMS-based adaptive denoising method for ECG signals.

BACKGROUND: Traditional least mean square algorithm (LMS) tends to converge faster and thus the larger the steady-state error of the algorithm. OBJECTIVE: In order to solve this issue, an improved adaptive normalized least mean square (NLMS) ECG signal denoising algorithm is proposed through utilizing the NLMS and the least mean square algorithm with added momentum term (MLMS). METHODS: The algorithm firstly performs LMS adaptive filtering on the original ECG signal. Then, the algorithm uses the relative error of the prior error signal and the posterior error signal before and after filtering to adaptively determine the iteration step factor. Finally, the expected error is set to determine whether the denoising meets the expected requirements. This method is applied to the MIT-BIH ECG database established by the Massachusetts Institute of Technology. RESULTS: Experimental results have shown that the proposed algorithm can achieve good denoising for the target signal, and the average signal to noise ratio (SNR) of the proposed method is 17.6016, the RMSE is only 0.0334, and the average smoothness index R is only 0.0325. CONCLUSION: The proposed algorithm effectively removes the original ECG signal noise, and improves the smoothness of the signal the denoising efficiency.

Glycyrrhizin mediated liver-targeted alginate nanogels delivers quercetin to relieve acute liver failure.

Acute liver failure is an uncommon and dramatic clinical syndrome with a high risk of mortality. Previous treatments existed some limitations of poor bioavailability and targeting the efficiency of drugs. In this study, a novel glycyrrhizin mediated liver-targeted alginate nanogels, which can deliver the antioxidant quercetin to the liver for the treatment of acute liver injury. In vitro radical scavenging results showed that the antioxidant activity of quercetin was increased 81-fold. The tissue distribution results indicated that glycyrrhizin-mediated nanogels showed stronger fluorescence intensity in the liver, which improved liver targeting and therapeutic efficacy. Quercetin-glycyrrhizin nanogels were more effective at restoring liver injury as indicated on serum markers, including alanine transaminase, aspartate aminotransferase, and total bilirubin. The histopathology result showed that quercetin-glycyrrhizin nanogels reversed liver damage. Oxidative parameters of malondialdehyde and glutathione s-transferase were decreased, which provided supporting evidence of antioxidation. Moreover, quercetin-glycyrrhizin nanogels were more effective in down-regulating the inflammation-related gene expression of tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase and monocyte chemotactic protein-1. In conclusion, the novel glycyrrhizin mediated liver-targeted alginate nanogels might be a promising treatment for acute liver failure.

coPLINK: A complementary tool to PLINK.

In genome-wide association studies (GWAS), a wide variety of analysis tools have been designed, leading to various formats of GWAS data. How to convert a dataset in non-PLINK format into PLINK format to use its powerful analysis performance, or to convert a dataset in PLINK format into the format of other analysis tools, is a problem that needs to be faced and solved. To address this issue, we developed a tool called coPLINK, a complementary tool to PLINK, to cooperate with PLINK to implement the conversions of GWAS data formats and to provide some additional functions, such as data files comparison. The tool can implement mutual conversions not only between an existing data format and PLINK PED/BED, but also between a user-defined data format and PLINK PED. The usage and performance of the tool are similar to PLINK. The characteristics of the conversions of existing data formats and user-defined formats make it be a good assistant to PLINK or other tools and, have good potential for GWAS studies or other works.

Incidence of lymph node metastasis at each station in Siewert types â ¡/â ¢ adenocarcinoma of the esophagogastric junction: A systematic review and meta-analysis.

The optimal extent of lymphadenectomy for adenocarcinoma of the esophagogastric junction (AEG) has been continuously debatable. The study aimed to determine the incidence of lymph node metastasis at each station in Siewert types Ⅱ/Ⅲ AEG. PubMed was searched and publications reporting metastasis at each nodal station were eligible. Meta-analysis was performed using RevMan 5.3. Twenty-one studies involving 4662 patients were included. The incidence of lymph node metastasis was high (≥20%) in stations No. 3, 1, 2 and 7 in decreasing order, and moderate (10-20%) in stations No. 9, 19 and 110. The incidence did not exceed 10% in stations No. 10, 11p, 20, 8a, 4sa, 4 s b and 4d, was less than 5% in stations No. 5, 6, 11d, 12a, and even close to 0 in stations No. 107, 111 and 112. Compared with type Ⅲ tumors, type Ⅱ tumors had significantly lower incidence in some abdominal stations including No. 3, 4sa, 4 s b, 6, 8a and 10, while significantly higher in the lower mediastinal stations. The present analysis established a map of lymph node metastasis in Siewert types Ⅱ/Ⅲ AEG, which may serve as a valuable reference for the extent of lymphadenectomy.

[Responses of soil respiration to temperature under different mulching modes in a dryland corn field]. / 不同覆盖方式下旱作玉米田土壤呼吸对温度变化的响应.

Based on a 9-year field experiment, soil samples under straw mulching (SM), plastic film mulching (FM) and no mulching (CK) were incubated at 15, 25 and 35 ℃ for 60 d to investigate the responses of soil respiration to warming and its temperature sensitivity. The results showed that during the whole incubation period, soil respiration rate exhibited a unimodal distribution, while the cumulative soil respiration increased with an "S" curve. The cumulative soil respiration during the first 30 d accounted for about 75%-85% of total during the whole incubation period. The cumulative SM increased by 19.4% compared with CK, whereas no difference was detected between CK and FM. At 25 ℃ and 35 ℃, the mean soil respiration rate increased by 17.0% and 36.8%, and the cumulative CO2 release of soil respiration increased by 13.1% and 33.6%, respectively, compared with 15 ℃. No interaction was detected between mulching method and temperature. 97.7%-99.9% of variation in soil respiration could be explained by temperature change, with soil respiration being positively correlated with organic carbon and total nitrogen content. Compared with no mulching and plastic film mulching, straw mulching could significantly promote soil respiration by increasing the input of organic matter in the soil, but reduced the temperature sensitivity of soil respiration. Straw mulching rather than plastic film mulching would be more efficient at reducing CO2 emission in the Loess Plateau dryland farming area under the context of global warming.

Density distribution of gene expression profiles and evaluation of using maximal information coefficient to identify differentially expressed genes.

The hypothesis of data probability density distributions has many effects on the design of a new statistical method. Based on the analysis of a group of real gene expression profiles, this study reveal that the primary density distributions of the real profiles are normal/log-normal and t distributions, accounting for 80% and 19% respectively. According to these distributions, we generated a series of simulation data to make a more comprehensive assessment for a novel statistical method, maximal information coefficient (MIC). The results show that MIC is not only in the top tier in the overall performance of identifying differentially expressed genes, but also exhibits a better adaptability and an excellent noise immunity in comparison with the existing methods.

Acetoacetate extract of pleione bulbocodioides (franch. ) rolfe induces apoptosis of human leukemia thp-1cells through a mitochondria-regulated intrinsic apoptotic pathway / Extrato de acetoacetato de Pleione bulbocodioides (Franch. ) Rolfe induz a apoptose de células THP-1 de leucemia humana através de uma via apoptótica intrínseca regulada por mitocôndrias

The tubers of three orchidaceous plants, includingPleione bulbocodioides (Franch.) Rolfe, have been used as 'Shan-Ci-Gu' in traditional Chinese medicine for the treatment of bacterial infections and cancers for thousands of years. In this study, the effects of an acetoacetate (EtOAc) extract of P. bulbocodioides on the cell viability and apoptosis of THP-1 (human acute monocytic leukemia cell line) cells and its interaction with possible apoptotic pathways were investigated. THP-1 cells were treated with the EtOAc extract of P. bulbocodioides at different concentrations. The results showed that THP-1 cell viability was significantly inhibited by the EtOAc extract ofP. bulbocodioides with an IC50 of 51.37±2.68 µ g/ mL at 24 h. The examination of cytotoxic effects on healthy cells showed that the EtOAc extract of P. bulbocodioidesdid not show any effect on healthy Vero cells. Selectivity indexes were greater than 15.57, suggesting that the EtOAc extract of P. bulbocodioides had selective toxicity against THP-1 cells. The results of annexin V-FITC/PI and DAPI staining showed that the EtOAc extract of P. bulbocodioides induced cell apoptosis in a dose-dependent manner. The apoptotic rate was increased in the treatment groups compared with that in the control group (P<0.05). The distribution of cells in the G2 phase of the cell cycle increased along with typical cell apoptosis-induced morphological changes. The levels of the pro-apoptotic proteins Bax, cleaved PARP and cleaved caspase-3 increased with increasing concentration of acetoacetate extract of P. bulbocodioides, while the anti-apoptosis protein Bcl-2 was downregulated. Cyt c and AIF, which are characteristic proteins of the mitochondria-regulated intrinsic apoptosis pathway, also increased in the cytosol with increasing concentrations of the EtOAc extract of P. bulbocodioides. These results showed that the EtOAc extract of P. bulbocodioidessignificantly inhibits cell viability and induces cell apoptosis in the human leukemia cell line THP-1 through a mitochondria-regulated intrinsic apoptotic pathway

Os tubérculos de três plantas orquidáceas, incluindo Pleione bulbocodioides (Franch.) Rolfe, têm sido usados como "Shan-Ci-Gu" na medicina tradicional chinesa para o tratamento de infecções bacterianas e cânceres por milhares de anos. Neste estudo, os efeitos de um extrato de acetoacetato (EtOAc) de P. bulbocodioides na viabilidade celular e apoptose de células THP-1 (linhagem celular de leucemia monocítica aguda humana) e sua interação com possíveis vias apoptóticas foram investigados. As células THP-1 foram tratadas com o extrato EtOAc de P. bulbocodioides em diferentes concentrações. Os resultados mostraram que a viabilidade das células THP-1 foi significativamente inibida pelo extrato EtOAc de P. bulbocodioides com IC50 de 51,37 ± 2,68 µ g/mL às 24 h. O exame dos efeitos citotóxicos em células saudáveis mostrou que oextrato de EtOAc de P. bulbocodioides não mostrou nenhum efeito sobre células Vero saudáveis. Os índices de seletividade foram maiores que 15,57, sugerindo que o extrato de EtOAc de P. bulbocodioides teve toxicidade seletiva contra as células THP-1. Os resultados da coloração da anexina V-FITC/PI e DAPI mostraram que o extrato de EtOAc de P. bulbocodioides induziu a apoptose celular de maneira dose-dependente. A taxa de apoptose foi aumentada nos grupos de tratamento em comparação com o grupo controle (P <0,05). A distribuição de células na fase G2 do ciclo celular aumentou juntamente com alterações morfológicas típicas induzidas pela apoptose celular. Os níveis das proteínas pró-apoptóticas Bax, PARP clivada e caspase-3 clivada aumentaram com o aumento da concentração do extrato acetoacetato de P. bulbocodioides, enquanto a proteína anti-apoptose Bcl-2 foi regulada negativamente. Cyt c e AIF, que são proteínas características da via de apoptose intrínseca regulada por mitocôndrias, também aumentaram no citosol com concentrações crescentes do extrato de EtOAc de P. bulbocodioides. Estes resultados mostraram que o extrato de EtOAc de P. bulbocodioides inibe significativamente a viabilidade celular e induz a apoptose na linha celular de leucemia humana THP-1 através de uma via apoptótica intrínseca regulada por mitocôndrias.

Mn-Induced Neurocytes Injury and Autophagy Dysfunction in Alpha-Synuclein Wild-Type and Knock-Out Mice: Highlighting the Role of Alpha-Synuclein.

Overexposure to manganese (Mn) is an important environmental risk factor for Parkinsonian-like symptoms referred to as manganism. Alpha-synuclein (α-Syn) oligomerization is a major cause in Mn-induced neurotoxicity. Autophagy, as an adjust response to control intracellular protein homeostasis, is involved in the degradation of α-Syn monomers or oligomers. Furthermore, autophagy dysregulation is also related to development of neurodegenerative disorders. Hence, we speculated that there was an interaction effect between α-Syn oligomerization and autophagy upon Mn exposure. In this study, we applied α-Syn gene knockout mice (α-Syn-/-) and wild-type mice (α-Syn+/+) treated with three different concentrations of MnCl2 (50, 100, and 200 µmol/kg) to elucidate the physiological role of α-Syn in Mn-induced autophagy dysregulation and neurocytes injury. We found that activation of chaperone-mediated autophagy (CMA) pathway by Mn was independent of α-Syn. Additionally, α-Syn could ameliorate excessive autophagy induced by high dose Mn (200 µmol/kg). Next, we used 5 mg/kg Rapamycin (Rap) or 3-methyladenine (3-MA) to regulate autophagy. The study revealed that autophagy is involved in Mn-induced α-Syn oligomerization and neurocytes injury. Taken together, these findings indicated that α-Syn oligomerization might be the major responsible for the Mn-induced autophagy dysregulation and neurocytes injury.

Cloning, expression prolife, and immune characterization of a novel stat family member (stat5bl) in Chinese tongue sole (Cynoglossus semilaevis).

STAT plays important roles in innate immunity during JAK/STAT signaling pathway, and STAT5 is particularly focused due to the existence of duplicated forms in fish and mammal. In Chinese tongue sole, stat5bl was suggested to be a candidate related to Vibrio harveyi resistance based on previous QTL screening. In this study, the full length of stat5bl cDNA was cloned and its expression patterns were analyzed. stat5bl was predominantly expressed in immune tissues, where the highest level was observed in liver, followed by skin and gill. Time course expression patterns were examined in six tissues (liver, skin, gill, kidney, intestine, spleen) after V. harveyi infection. stat5bl could be up-regulated by V. harveyi infection in all tissues except liver, despite the timepoints of peak were different. In contrast, stat5bl was significantly downregulated in liver. To elucidate the role of stat5bl in liver, in vitro RNAi were performed using primary liver cell culture. Knockdown of stat5bl could regulate the expression of genes closely related to JAK/STAT pathway. This study would enlarge our understanding of stat5bl in fish immunity.