[Effects of Biochar Application on the Structure and Function of Fungal Community in Continuous Cropping Watermelon Soil].

This study was conducted to clarify the long-term effects of biochar application on the structure and function of the fungal community in continuous cropping watermelon soil. Taking watermelon root soil as the research object, Illumina NovaSeq high-throughput sequencing and FUNGuild platform were used to analyze the differences in soil fungal community composition, diversity, and function after 3-year biochar additions of 7.5, 15.0, and 30.0 t·hm-2 and to explore the correlation between soil environmental factors and fungal community structure under the control of biochar. The results showed that compared to that in the absence of biochar (control), the soil pH, available phosphorus, available potassium, total nitrogen, organic matter, and cation exchange capacity increased, but available nitrogen decreased with biochar addition. High-throughput sequencing results showed that biochar amendment improved the fungal community structure in continuous cropping watermelon soil and increased the richness and diversity of soil fungi. A total of 922 OTU were obtained from all soil samples, and the species annotation results indicated that the dominant fungal groups were Ascomycota, Basidiomycota, Mortierellomycota, Chytridiomycota, and Glomeromycota, with these phyla accounting for 85.70 %-92.45 % of the total sequences.The relative abundance of Ascomycota and Basidiomycota decreased, whereas the abundance of Mortierellomycota and Glomeromycota increased with biochar addition.At the genus level, the application of biochar increased the relative abundance of Mortierella and Rhizophlyctis but decreased the abundance of Fusarium. The Mantel test showed that soil available potassium, available nitrogen, organic matter, and pH were the main environmental factors leading to the shift in the soil fungal community composition.The functional prediction with FUNGuild showed that the many nutrient types among the different treatments were saprotrophic, pathotrophic, and symbiotrophic. The relative abundance of pathotrophs significantly decreased, but the abundance of symbiotrophs significantly increased with the medium and high doses of biochar treatment. In conclusion, the application of biochar changed the soil physicochemical properties, promoted the development of soil fungal community structure and functional groups in a healthy and beneficial direction, and improved the quality of continuous cropping watermelon soil.

A systematic review and meta-analysis comparing intrawound vancomycin powder and povidone iodine lavage in the prevention of periprosthetic joint infection of hip and knee arthroplasties.

BACKGROUND: Focus on reviewing a vigorous research effort to improve the safety profile of vancomycin powder (VP) and its optimal dose in reducing periprosthetic joint infection (PJI) is the need of the hour. This systematic review and meta-analysis attempt to explore the ongoing use of VP and VP + povidone iodine (PI) lavage to prevent PJI of hip/knee arthroplasties and highlights its challenges among the orthopedic community about the existence of the major organism and its frequency in total joint arthroplasty (TJA) patients. METHODS: We searched PubMed/MEDLINE, EMBASE databases regarding the outcomes of vancomycin powder (VP) and VP + povidone iodine (PI) combination in preventing periprosthetic joint infection of hip and knee arthroplasties. RESULTS: In 5 of 7 studies, the combination of vancomycin powder (VP) and povidone iodine (PI) lavage have shown a lower risk of periprosthetic joint infection (PJI) in acute and high-risk hip and knee arthroplasties patients, with less or without serious adverse events and readmissions; while four of seven studies using VP-only found increasing rates of PJI in primary total knee arthroplasty and partial hip replacement in elderly patients with comorbidities, and significantly causes aseptic wound complications compared to the control group. CONCLUSIONS: Intra-articular vancomycin powder (VP) and povidone iodine (PI) lavage showed a significant reduction of periprosthetic joint infection in primary and revision total joint arthroplasty. Before its widespread use in clinical settings, prospective randomized studies and, most importantly, its long-term efficacy and safety are recommended.

Study on crack evolutional behavior of rocks in triaxial compression based on colony growth dynamics model.

The crack propagation behavior of rock during compression involves complex mechanisms. Describing the growth behavior of a large number of cracks with conventional mechanical models is a major challenge. Therefore, in this work, we propose a new method to describe crack growth behavior by considering crack bodies as free voxels that can expand and coalesce within a rock sample according to certain rules. Specifically, we first propose a crack growth model that quantitatively describes the crack growth ratio and crack growth rate, which are integrally related to the loading rate, internal friction angle, cohesion, initial porosity, and confining stress. Second, to avoid the complex analytical process of the traditional mechanical model in solving the propagation directions of multiple cracks, we introduce a method for determining the crack growth directions of shearing failure based on the colony growth assumption. This method defines the crack propagation direction as a synthetic vector of the inertial direction, the attractive direction, the Coulomb direction, and the edge direction. Moreover, a new mathematical description method of fracture energy and plastic energy is proposed to calculate the crack growth at each time step. The simulation results show that our crack growth model for shearing failure agrees well with the experimental results and explains the fracture behavior and transformation law of cracks to some extent.

Construction and validation of a m6A RNA methylation and ferroptosis-related prognostic model for pancreatic cancer by integrated bioinformatics analysis.

Background: Both N6-methyladenosine (m6A) ribonucleic acid (RNA) methylation and ferroptosis regulators are demonstrated to have significant effects on the malignant clinicopathological characteristics of pancreatic adenocarcinoma (PAAD) patients. However, the currently available clinical indexes are not sufficient to predict precise prognostic outcomes pf PAAD patients accurately. This study aims to examine the clinicopathologic features of m6A RNA methylation and ferroptosis regulators in predicting the outcomes of different types of cancer. Methods: As the foundation for this research, the differentially expressed genes (DEGs) between PAAD tissues and adjacent normal tissues were first identified. Next, dimensional reduction analysis (DCA) based on m6A RNA methylation regulators and ferroptosis regulators were performed and DEGs between good/poor prognosis PAAD patient clusters were identified. DEGs were then screened by Cox analysis, and finally a risk signature was established by least absolute shrinkage and selection operator (LASSO) analyses. The prediction model based on risk score was further evaluated by a validation set from Gene Expression Omnibus (GEO) database. Results: In total, 4 m6A RNA methylation regulator genes and 29 ferroptosis regulator genes were found to have close causal relationships with the prognosis of PAAD, and a risk score with 3 m6A methylation regulators (i.e., IGF2BP2, IGF2BP3, and METTL16) and 4 ferroptosis regulators (i.e., ENPP2, ATP6V1G2, ITGB4, and PROM2) was constructed and showed to be highly involved in PAAD progression and could serve as effective markers for prognosis with AUC value equaled 0.753 in training set and 0.803 in validation set. Conclusions: The combined prediction model, composed of seven regulators of m6A methylation and ferroptosis, in this study more effectively reflects the progression and prognosis of PAAD than previous single genome or epigenetic analysis. Our study provides a broader perspective for the subsequent establishment of prognostic models and the patients may benefit from more precision management.

[Effect of Family Function on Suicide-Related Behaviors of Junior Middle School Students: The Mediating Effect of Depression].

Objective: To examine the prevalence of suicide-related behaviors among junior middle school students, and to explore the mediating role of depression in the relationship between suicide-related behaviors and family function. Methods: A total of 2572 junior middle school students from three middle schools in Chengdu were interviewed face-to-face by using suicide-related items from Youth Risk Behavior Surveillance System (YRBSS), Chinese Family Assessment Instrument (C-FAI), and Center for Epidemiologic Studies Depression Scale for Children (CES-DC). The mediating role of depression was analyzed with structural equation model. Results: The prevalence of suicide-related behaviors was 26.01% among the respondents. The prevalence of suicide ideation, suicide plan and suicide attempt were 24.38%, 13.49% and 10.77%, respectively. Depression played a partial mediating role in how family function impacted on suicide-related behaviors, presenting a direct effect value of 0.170 (95% CI: 0.117-0.218, P<0.001) and an indirect effect value of 0.205 (95% CI: 0.176-0.234, P<0.001), with the mediating effect accounting for 54.67% of the total effect. Conclusion: Poor family function may increase the risk of suicide-related behaviors, and this effect is produced mostly through the impact on children's mental health. Improving family function will not only improve children's psychological status, but also reduce suicide-related behaviors.

Lateral epicondyle osteotomy approach vs. olecranon osteotomy approach: an anatomic study of cadavers.

BACKGROUND: Exposure of the articular surface is the key to successful open reduction and internal fixation treatment for coronal shear fractures of the distal humerus. The olecranon osteotomy approach has previously been described as one of the most effective exposure approaches. Nevertheless, this approach cannot expose the anterior trochlea, and it is impossible to reduce and fix the capitellum under direct vision. The purpose of this study was to compare the exposure of the articular surface of the distal humerus between the lateral epicondyle osteotomy approach (group L) and the olecranon osteotomy approach (group O). METHODS: Each approach was performed on 8 freshly frozen upper limbs of adult cadavers. After each approach was completed, a 0.5-mm Kirschner wire is inserted along the edge to mark the visible part of the articular surface. Then, the soft tissue of each elbow is removed, and a surface-scanning system is used to create a digital 3-dimensional model. The visible part of the articular surface obtained by each surgical approach was mapped and quantified using markers created by Kirschner wires. RESULTS: The lateral epicondyle osteotomy approach and the olecranon osteotomy approach exposed 0.8 ± 0.0 and 0.6 ± 0.0 of the distal humeral articular surface (P < .001), 1.0 ± 0.0 and 0.3 ± 0.1 of the capitellum (P < .001), 0.6 ± 0.0 and 0.7 ± 0.0 of the trochlea (P < .001), 0.7 ± 0.0 and 0.5 ± 0.1 of the anterior trochlea (P < .001), and 0.5 ± 0.0 and 1.0 ± 0.0 of the posterior trochlea, respectively (P < .001). CONCLUSION: Compared with the olecranon osteotomy approach, the lateral epicondyle osteotomy approach could more fully expose the total articular surface of the distal humerus, capitellum, and anterior trochlea, but the olecranon osteotomy approach could more fully expose the trochlea and posterior trochlea.

Respiratory tract infections in children with allergic asthma on allergen immunotherapy during influenza season.

To describle how respiratory tract infections (RTIs) that occurred in children with allergic asthma (AA) on allergen immunotherapy (AIT) during an influenza season. Data including clinical symptoms and treatment history of children (those with AA on AIT and their siblings under 14 years old), who suffered from RTIs during an influenza season (Dec 1st, 2019-Dec 31st, 2019), were collected (by face to face interview and medical records) and analyzed. Children on AIT were divided into 2 groups: stage 1 (dose increasing stage) and stage 2 (dose maintenance stage). Their siblings were enrolled as control. During the study period, 49 children with AA on AIT (33 patients in stage 1 and 16 patients in stage 2) as well as 49 children without AA ( their siblings ) were included. There were no significant differences in occurrences of RTIs among the three groups (p > 0.05). Compared with children in the other two groups, patients with RTIs in stage 2 had less duration of coughing and needed less medicine. Children on AIT with maintenance doses had fewer symptoms and recovered quickly when they were attacked by RTIs, which suggested that AIT with dose maintenance may enhance disease resistance of the body.

Esophageal Scab Mimicking a Parasite: A Case Report.

BACKGROUND Parasitic helminths in the esophagus are rare. Here, we report a case of esophageal scab mimicking a parasite. CASE REPORT A 65-year-old man was admitted to our hospital because after choking on food. Gastroscopy showed 2 foreign bodies adherent to the esophagus wall 28 and 34 cm from the incisor, which appeared to be a fluke. Two fluke-like foreign bodies (1.5 and 1.8 cm in length) were removed from the esophageal ulcer with forceps. After fixation with alcohol, the suspected fluke-like foreign bodies were noted to be brown and woody. Under a light microscope, the structure of the foreign body was not apparent, and no typical flatworm tegument structure was demonstrated on pathologic sections, but it had a blood clot-like structure. Administration of albendazole did not expel any helminths. A stool examination showed no eggs of the putative flukes. The genomic DNA of the suspected flukes was extracted and a 700 bp fragment was amplified by universal barcoding primers. The sequencing showed that the homology with human cytochrome c oxidase subunit I gene was 98.8%. CONCLUSIONS The scab formed by the esophageal ulcer was identified based on clinical manifestations, anti-helminth and stool examinations, parasite morphology, and molecular biology. Our experience with this case suggests that the universal barcoding technique can be used for identification of foreign bodies suspected to be parasites.

Salidroside and FG-4592 ameliorate high glucose-induced glomerular endothelial cells injury via HIF upregulation.

Increasing research indicates that hyperglycemia plays a crucial role in the progression of diabetic nephropathy (DN); however, effective treatment for preventing or slowing DN progression are seriously lacking. Although salidroside (SAL) has been demonstrated to have a positive anti-diabetic effect, the cellular mechanisms remain unclear. FG-4592, a novel prolyl hydroxylase inhibitor, was used to regulate HIF-1α and HIF-2α expression. The present study aimed to explore the underlying mechanisms of SAL and FG-4592 on high glucose (HG)-induced rat glomerular endothelial cells (rGECs) injury. HG-cultured rGECs were used to induce a diabetic environment. An MTT assay, RT-qPCR, Western blot, flow cytometry, and immunofluorescent staining were performed to investigate the effects of SAL on HG-induced rGECs injury. FG-4592 and SAL protected rGECs against HG-induced injury by increasing cellular viability and reducing the cell apoptosis rate. SAL and FG-4592 downregulated PHD-2 expression and upregulated HIF-1α and HIF-2α expression. In conclusion, our findings suggest that SAL and FG-4592 ameliorate HG-induced rGEC injury by upregulating HIF expression, indicating that SAL and FG-4592 might be favorable for further DN-treatment.

Alkyl Carbagermatranes Enable Practical Palladium-Catalyzed sp2-sp3 Cross-Coupling.

Pd-catalyzed cross-coupling reactions have achieved tremendous accomplishments in the past decades. However, C(sp3)-hybridized nucleophiles generally remain as challenging coupling partners due to their sluggish transmetalation compared to the C(sp2)-hybridized counterparts. While a single-electron-transfer-based strategy using C(sp3)-hybridized nucleophiles had made significant progress recently, fewer breakthroughs have been made concerning the traditional two-electron mechanism involving C(sp3)-hybridized nucleophiles. In this report, we present a series of unique alkyl carbagermatranes that were proven to be highly reactive in cross-coupling reactions with our newly developed electron-deficient phosphine ligands. Generally, secondary alkyl carbagermatranes show slightly lower, yet comparable activity to its Sn analogue. Meanwhile, primary alkyl carbagermatranes exhibit high activity, and they were also proved stable enough to be compatible with various reactions. Chiral secondary benzyl carbagermatrane gave the coupling product under base/additive-free conditions with its configuration fully inversed, suggesting that transmetalation was carried out in an "SE2(open) Inv" pathway, which is consistent with Hiyama's previous observation. Notably, the cross-coupling of primary alkyl carbagermatranes could be performed under base/additive-free conditions with excellent functional group tolerance and therefore may have potentially important applications such as stapled peptide synthesis.

Different techniques for harvesting grafts for living donor liver transplantation: A systematic review and meta-analysis.

AIM: To perform a systematic review and meta-analysis on minimally vs conventional invasive techniques for harvesting grafts for living donor liver transplantation. METHODS: PubMed, Web of Science, EMBASE, and the Cochrane Library were searched comprehensively for studies comparing MILDH with conventional living donor hepatectomy (CLDH). Intraoperative and postoperative outcomes (operative time, estimated blood loss, postoperative liver function, length of hospital stay, analgesia use, complications, and survival rate) were analyzed in donors and recipients. Articles were included if they: (1) compared the outcomes of MILDH and CLDH; and (2) reported at least some of the above outcomes. RESULTS: Of 937 articles identified, 13, containing 1592 patients, met our inclusion criteria and were included in the meta-analysis. For donors, operative time [weighted mean difference (WMD) = 20.68, 95%CI: -6.25-47.60, P = 0.13] and blood loss (WMD = -32.61, 95%CI: -80.44-5.21, P = 0.18) were comparable in the two groups. In contrast, analgesia use (WMD = -7.79, 95%CI: -14.06-1.87, P = 0.01), postoperative complications [odds ratio (OR) = 0.62, 95%CI: 0.44-0.89, P = 0.009], and length of hospital stay (WMD): -1.25, 95%CI: -2.35-0.14, P = 0.03) significantly favored MILDH. No differences were observed in recipient outcomes, including postoperative complications (OR = 0.93, 95%CI: 0.66-1.31, P = 0.68) and survival rate (HR = 0.96, 95%CI: 0.27-3.47, P = 0.95). Funnel plot and statistical methods showed a low probability of publication bias. CONCLUSION: MILDH is safe, effective, and feasible for living donor liver resection with fewer donor postoperative complications, reduced length of hospital stay and analgesia requirement than CLDH.

[Efficiency of Trichoderma longibrachiatum T6 in the control of Meloidogyne incognita and its rhizosphere colonization in cucumber].

Efficiency of different concentrations of Trichoderma longibrachiatum T6 against Meloidogyne incognita and its rhizosphere colonization in cucumber were determined in greenhouse experiments. The results of rhizosphere colonization experiments showed that the number of colonies in cucumber soil and root increased significantly ten weeks after inoculation with the second stage juveniles of M. incognita and different concentrations of T. longibrachiatum T6, and there was significant difference in different concentrations of T. longibrachiatum T6, e.g., the maximum numbers of colonies in soil and root were 7.8 x 107 and 6.3 x 105 CFU · mL⁻¹ respectively after treated with the spore suspension of 1.5 x 107 CFU · mL⁻¹. Greenhouse experiments results showed that different concentrations of T. longibrachiatum T6 had significant control effect on different life stages of M. incognita, and the control effect increased with the concentration of T. longibrachiatum T6. T. longibrachiatum T6 significantly increased plant height, root length, above-ground and root fresh mass o cucumber inoculated by M. incognita. T. longibrachiatum T6 could colonize in cucumber rhizosphere, had control effect on M. incognita, and significantly improved the growth of cucumber.

[Effects of selenite addition on selenium absorption, root morphology and physiological characteristics of rape seedlings].

Abstract: The rape (Brassica napus L. cv. Xiangnongyou 571) was chosen as the experimental material to undergo solution cultivation at seedling stage to investigate the effects of selenite addition on the selenium (Se) absorption and distribution, root morphology and physiological characteristics of rape seedlings. The results showed that the bioaccumulation ability of Se decreased significantly with increasing the Se application rate, but the Se distribution coefficient remained around 0.9 with no significant influence. The application of 10 µmol . L-1 selenite stimulated the growth of rape seedlings through improving the root physiological characteristics and root morphology significantly, including significantly increasing the production of superoxide radical (O2∙-) rate and the activities of superoxide dismutase (SOD), peroxidase (POD) and fungal catalase (CAT) in the root system, which resulted in a reduction of the lipids peroxidation (MDA) content as much as 26.0%, consequently increasing the root activity as much as 17.4%. The promoting degrees of selenite on root morphological parameters were from strong to weak in such a tendency: root volume > total surface area > number of root forks > total root length > number of root tips > average diameter. However, such positive effects had no significant difference with those in treatment with 1 µmol . L-1 selenite, indicating that small amounts (≤ 10 Lmol . L-1) of selenite were able to increase the activity of antioxidant enzymes and reduce the content of MDA in root system, which could increase root activity and improve root morphology, hence increased the biomass of rape seedlings.

The role of quality of care and attitude towards disability in the relationship between severity of disability and quality of life: findings from a cross-sectional survey among people with physical disability in China.

BACKGROUND: People with physical disability (PWPD) is the largest subgroup of people with disability (PWD) in China, but few studies have been conducted among this vulnerable population. The objective of this study was to investigate the level of quality of life (QoL), self-perceived quality of care and support (QOCS), severity of disability and personal attitude towards disability among people with physical disability in China, as well as to identify how QoL can be affected by severity of disability through QOCS and personal attitude towards disability among PWPD. METHODS: A cross-sectional study was conducted among 1,853 PWPD in Guangzhou, China. Data were collected on participants' QoL, QOCS, personal attitude towards disability and severity of disability. Structural equation modeling was used to examine the effects of the other variables on QoL. RESULTS: Even with a mild disability (mean score:1.72), relatively low levels of QoL (mean score: 2.65- 3.22) and QOCS (mean score: 2.95 to 3.28), as well as unfavorable personal attitude towards disability (mean score: 2.75 to 3.36) were identified among PWPD. According to SEM, we found that the influence of severity of physical disability on QoL is not only exerted directly, but is also indirectly through QOCS and their personal attitudes towards disability, with QOCS playing a more important mediating role than PWPD's attitudes towards their own disability. CONCLUSIONS: Unfavorable health status was identified among PWPD in China. Focusing on improvement of assistance and care services has the potential to substantially improve PWPD's QoL. Further research should focus on understanding the needs and their current state of health care of PWPD in China thus being able to develop better interventions for them.

miR-335 and miR-363 regulation of neuroblastoma tumorigenesis and metastasis.

BACKGROUND: microRNA (miRNA) functions broadly as post-transcriptional regulators of gene expression, and disproportionate miRNAs can result in dysregulation of oncogenes in cancer cells. We have previously shown that gastrin-releasing peptide receptor (GRP-R) signaling regulates tumorigenicity of neuroblastoma cells. Herein, we sought to characterize miRNA profile in GRP-R silenced neuroblastoma cells, and to determine the role of miRNAs on tumorigenicity and metastatic potential. METHODS: Human neuroblastoma cell lines, BE(2)-C and SK-N-SH, were used for our study. Stably transfected GRP-R silenced cells were assessed for miRNA profiles. Cells were transfected with miR-335, miR-363, or miR-CON, a nontargeting control, and in vitro assays were performed. In vivo functions of miR-335 and miR-363 were also assessed in a spleen-liver metastasis murine model. RESULTS: GRP-R silencing significantly increased expression of miR-335 and miR-363 in BE(2)-C cells. Overexpression of miR-335 and miR-363 decreased tumorigenicity as measured by clonogenicity, anchorage-independent growth, and metastasis determined by cell invasion assay and liver metastasis in vivo. CONCLUSION: We report, for the first time, that GRP-R-mediated tumorigenicity and increased metastatic potential in neuroblastoma are regulated, in part, by miR-335 and miR-363. A better understanding of the anti-tumor functions of miRNAs could provide valuable insights to discerning molecular mechanisms responsible for neuroblastoma metastasis.

Differential regulation of cyclin-dependent kinase inhibitors in neuroblastoma cells.

Gastrin-releasing peptide (GRP) and its receptor (GRP-R) are highly expressed in undifferentiated neuroblastoma, and they play critical roles in oncogenesis. We previously reported that GRP activates the PI3K/AKT signaling pathway to promote DNA synthesis and cell cycle progression in neuroblastoma cells. Conversely, GRP-R silencing induces cell cycle arrest. Here, we speculated that GRP/GRP-R signaling induces neuroblastoma cell proliferation via regulation of cyclin-dependent kinase (CDK) inhibitors. Surprisingly, we found that GRP/GRP-R differentially induced expressions of p21 and p27. Silencing GRP/GRP-R decreased p21, but it increased p27 expressions in neuroblastoma cells. Furthermore, we found that the intracellular localization of p21 and p27 in the nuclear and cytoplasmic compartments, respectively. In addition, we found that GRP/GRP-R silencing increased the expression and accumulation of PTEN in the cytoplasm of neuroblastoma cells where it co-localized with p27, thus suggesting that p27 promotes the function of PTEN as a tumor suppressor by stabilizing PTEN in the cytoplasm. GRP/GRP-R regulation of CDK inhibitors and tumor suppressor PTEN may be critical for tumoriogenesis of neuroblastoma.

Akt2 regulates metastatic potential in neuroblastoma.

Activation of PI3K/AKT pathway correlates with poor prognosis in patients with neuroblastoma. Our previous studies have demonstrated that PI3K/AKT signaling is critical for the oncogenic transformations induced by gastrin-releasing peptide (GRP) and its receptor, GRP-R, in neuroblastoma. Moreover, PI3K/AKT-dependent oncogenic transformations require N-myc, an extensively studied oncogene in neuroblastoma. Whether AKT directly regulates the expression of N-myc oncogene is yet to be determined. Here, we report a novel finding that of the three AKT isoforms, AKT2 specifically regulated N-myc expression in neuroblastoma cells. We also confirmed that GRP-R is upstream of AKT2 and in turn, regulated N-myc expression via AKT2 in neuroblastoma cells. Functional assays demonstrated that attenuation of AKT2 impaired cell proliferation and anchorage-independent cell growth, and decreased the secretion of angiogenic factor VEGF in vitro. Furthermore, silencing AKT2 inhibited migration and invasion of neuroblastoma cells in vitro. Xenografts established by injecting AKT2 silenced human neuroblastoma cells into murine spleen expressed decreased levels of AKT2 and resulted in fewer liver metastases compared to controls in vivo. Hence, our study highlights the potential molecular mechanism(s) mediating the oncogenic role of GRP/GRP-R and demonstrates a novel role for AKT2 in neuroblastoma tumorigenesis, indicating that targeting the GRP/GRP-R/AKT2 axis may be important for developing novel therapeutics in the treatment of clinically aggressive neuroblastoma.

PI3K/AKT and ERK regulate retinoic acid-induced neuroblastoma cellular differentiation.

Neuroblastoma, the most common extra-cranial solid tumor in infants and children, is characterized by a high rate of spontaneous remissions in infancy. Retinoic acid (RA) has been known to induce neuroblastoma differentiation; however, the molecular mechanisms and signaling pathways that are responsible for RA-mediated neuroblastoma cell differentiation remain unclear. Here, we sought to determine the cell signaling processes involved in RA-induced cellular differentiation. Upon RA administration, human neuroblastoma cell lines, SK-N-SH and BE(2)-C, demonstrated neurite extensions, which is an indicator of neuronal cell differentiation. Moreover, cell cycle arrest occurred in G1/G0 phase. The protein levels of cyclin-dependent kinase inhibitors, p21 and p27(Kip), which inhibit cell proliferation by blocking cell cycle progression at G1/S phase, increased after RA treatment. Interestingly, RA promoted cell survival during the differentiation process, hence suggesting a potential mechanism for neuroblastoma resistance to RA therapy. Importantly, we found that the PI3K/AKT pathway is required for RA-induced neuroblastoma cell differentiation. Our results elucidated the molecular mechanism of RA-induced neuroblastoma cellular differentiation, which may be important for developing novel therapeutic strategy against poorly differentiated neuroblastoma.

[Study on synthesis and fluorescence characterization of europium and terbium complexes of 1-(5-(2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl) ethanone].

Six solid complexes(TbL3 x 2H2O, TbL2 (phen) x H2O, TbL2 (TPPO), EuL3 x 2H2O, EuL2 (phen) x 2H2O and EuL2 (TPPO) x 2H2O) have been synthesized based on the pyrazole ligand(HL)(phen = 1,10-phenanthroline, TPPO = Tri-phenylphosphine oxide, HL=1-(5-(2-hydroxyphenyl)-3-methyl-4,5-dihydropyrazol-1-yl) ethanone). These complexes were characterized by elemental analysis, IR spectra, and fluorescence spectra. The IR spectra indicated that all complexes exhibited the characteristic peaks of asymmetric stretching vibration v (C=O) and symmetric stretching vibration v (C=N) peaks. The C=O stretching band at 1,644 cm(-1) of HL molecule shifted to lower band in the complexes. The O-H band at 3,072 of the HL ligand is also shifted to lower band. All these shifts indicated that carbonyl group, O-H and C=N take part in coordinating with the rare-earth ion in the form of bridging tridentate. The excitation and emission spectra of the six complexes were determined at room temperature and the results show that EuL2 (Phen) x 2H2O and TbL2 (Phen) X 2H2O display the strongest relative fluorescence intensity with the excited bands at 310 and 320 nm, respectively. Meanwhile, the emission intensities of Eu3+ and Tb3+ complexes were greatly sensitized by phen.

[Application of multilevel models in the evaluation of bioequivalence (II).].

The main purpose of this paper is to explore the applicability of multivariate multilevel models for bioequivalence evaluation. Using an example of a 4 x 4 cross-over test design in evaluating bioequivalence of homemade and imported rosiglitazone maleate tablets, this paper illustrated the multivariate-model-based method for partitioning total variances of ln(AUC) and ln(C(max)) in the framework of multilevel models. It examined the feasibility of multivariate multilevel models in directly evaluating average bioequivalence (ABE), population bioequivalence (PBE) and individual bioequivalence (IBE). Taking into account the correlation between ln(AUC) and ln(C(max)) of rosiglitazone maleate tablets, the proposed models suggested no statistical difference between the two effect measures in their ABE bioequivalence via joint tests, whilst a contradictive conclusion was derived based on univariate multilevel models. Furthermore, the PBE and IBE for both ln(AUC) and ln(C(max)) of the two types of tablets were assessed with no statistical difference based on estimates of variance components from the proposed models. Multivariate multilevel models could be used to analyze bioequivalence of multiple effect measures simultaneously and they provided a new way of statistical analysis to evaluate bioequivalence.