The Exact Morphology of the Species Ephemera pieli Navás, 1934 from Eastern China (Ephemeroptera: Ephemeridae).

The original description and outline figure of the mayfly Ephemera pieli Navás, 1934, were based on male subimagoes, and its morphology and taxonomic status have not been confirmed since then. However, recently collected materials from eastern China, including all stages of this mayfly, reveal several unique characteristics that indicate E. pieli is a valid species in the subgenus Ephemera (Ephemera). These characteristics include forewings with numerous dark dots, hindwings or hind wingpads with one or two distinct median dots, penes covered mostly by the subgenital plate, and the apex of the penis bluntly extended. A neotype is designated.

Analysis of a Chinese pedigree affected with Hereditary coagulation factor Ⅻ deficiency due to compound heterozygous variants of F12 gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotypes and genetic variants of a Chinese pedigree affected with Hereditary coagulation factor Ⅻ (FⅫ) deficiency.@*METHODS@#A pedigree presented at the First Affiliated Hospital of Air Force Medical University on December 24,2021 was selected as the study subject. Activated partial thromboplastin time (APTT) and coagulation factor Ⅻ activity (FⅫ:C) were determine by a clotting method, and FⅫ antigen was detected with an ELISA assay. Following the extraction of genomic DNA, all exons and flanking regions of the F12 gene were subjected to Sanger sequencing. Clustalx-2.1-win, PROVEAN and Swiss-PDB Viewer software was used to analyze the conservation of amino acids at the variant sites, impact of of the variants on the amino acid substitutions and the protein structure.@*RESULTS@#The APTT of the proband has prolonged to 70.2 s. Her FⅫ:C and FⅫ:Ag have decreased to 12% and 13%, respectively. DNA sequencing revealed that the proband has harbored c.346G>A (p.Gly97Ser) and c.1583C>A (p.Ser509Tyr) heterozygous compound missense variants in exons 5 and 13 of the F12 gene, respectively. Her father and sister were heterozygous carriers for the c.346G>A (p.Gly97Ser) variant, whilst her mother and brother were heterozygous for the c.1583C>A (p.Ser509Tyr) variant.@*CONCLUSION@#The c.346G>A (p.Gly97Ser) and c.1583C>A (p.Ser509Tyr) compound heterozygous variants of the F12 gene probably underlay the pathogenesis of hereditary coagulation FⅫ deficiency in this pedigree.

Analysis of Structural Health Monitoring Data with Correlated Measurement Error by Bayesian System Identification: Theory and Application.

Measurement error is non-negligible and crucial in SHM data analysis. In many applications of SHM, measurement errors are statistically correlated in space and/or in time for data from sensor networks. Existing works solely consider spatial correlation for measurement error. When both spatial and temporal correlation are considered simultaneously, the existing works collapse, as they do not possess a suitable form describing spatially and temporally correlated measurement error. In order to tackle this burden, this paper generalizes the form of correlated measurement error from spatial correlation only or temporal correlation only to spatial-temporal correlation. A new form of spatial-temporal correlation and the corresponding likelihood function are proposed, and multiple candidate model classes for the measurement error are constructed, including no correlation, spatial correlation, temporal correlation, and the proposed spatial-temporal correlation. Bayesian system identification is conducted to achieve not only the posterior probability density function (PDF) for the model parameters, but also the posterior probability of each candidate model class for selecting the most suitable/plausible model class for the measurement error. Examples are presented with applications to model updating and modal frequency prediction under varying environmental conditions, ensuring the necessity of considering correlated measurement error and the capability of the proposed Bayesian system identification in the uncertainty quantification at the parameter and model levels.

Development and clinical application of 3D visualization-guided patient positioning system for radiotherapy / 中华放射医学与防护杂志

Objective:To develop a 3D visualization technology-assisted patient positioning system for radiotherapy and compare it with traditional patient positioning method for breast and pelvic radiotherapy.Methods:A total of 40 patients receiving radiotherapy in Changzhou No.2 People′s Hospital from June 2020 to April 2021 were selected for this study, including 20 patients with breast cancer and 20 patients with pelvic cancer.3D visualization reconstruction was carried out using the CT data of the patients for positioning. Then the 3D visualization models were integrated with the real treatment environment and were then shifted to the isocentral positions of accelerators through interactive operations. Based on this, the patients were actually positioned. Every week, all of the patients were firstly treated with traditional positioning, followed by 3D visualization-guided positioning. As a result, 240 times of positioning data of all patients were collected in three weeks. They were compared with the data of cone-beam CT(CBCT)-guided positioning, which served as the gold standard.Results:The absolute positioning errors of 3D visualization-guided positioning along x, y and z axes were (1.92±1.23), (2.04±1.16), and (1.77±1.37)mm, respectively for patients with breast cancer and were (2.07±1.08), (1.33±0.88), and (1.99±1.25)mm, respectively for patients with pelvic cancer. Compared with traditional positioning method , the accuracy of 3D visualization-guided positioning along x、 y, and z axes was increased by 38.83%, 52.40% and 33%, respectively for patients with breast cancer and was improved by 36.84%, 54.04% and 52.58% for patients with pelvic cancer, with all differences being statistically significant along y and z axes ( t=2.956-5.734, P< 0.05). Meanwhile, the error distribution of the two positioning method was statistically significant along in y axis for patients with breast cancer( χ2=7.481, P<0.05) and was statistically significant along each axis for patients with pelvic cancer( χ2=5.900, 6.415, 7.200, P<0.05). Conclusions:The positioning method guided by 3D visualization technology can effectively improve the positioning accuracy of patients with breast cancer and patients with pelvic cancer and is of value in potential clinical application.

Study of volume resolution of prostate motion target by four-dimensional ultrasound / 中华放射肿瘤学杂志

Objective:To explore the volume resolution of prostate motion target by four-dimensional (4D) ultrasound.Methods:The prostate ultrasound model was selected, and the group comparison study was conducted using 4D ultrasound to outline the prostate target under different motion amplitudes (A) and motion period (T). The simulated A value was set as 0.5 mm, 1 mm, 2 mm, 3 mm, 4 mm, and 5 mm, respectively. The T value was set as 1 s, 2 s, 3 s, and 4 s, respectively. The volume of the target of the model prostate was calculated, and the static ultrasound image of the target was used as the control group to analyze the difference between two groups.Results:When the model was still, the size of the target of ultrasound was consistent with that of CT scan ( P>0.05). When the A values were 0.5 mm and 1 mm, there was no statistical difference between the volume in period 1-4 s and the volume in the target at rest (all P>0.05). When the A values were 2 mm and 3 mm, and the T values were 1 s, 2 s and 3 s there was statistical difference between the volume of target and that of of static ultrasonic target (all P<0.05). When the A value was 2 mm and the T value was 4 s, there was no statistical difference between the target volume and the static target volume ( P=0.710). The range within the group was 6.7 cm 3, and the standard deviation was 1.15 cm 3. When the A value was 3 mm and the T value was 4 s, the volume repeatability of the target was poor, and the range within the group was 14.4 cm 3; when the A values were 4 mm and 5 mm, and the T values were 1-4 s, the range within the group was 3.27-17.63 cm 3 and 6.51-21.02 cm 3, respectively. The volume repeatability of the target under each period was extremely poor, which could not meet the clinical requirements. Conclusion:4D ultrasound can provide reliable reference data for patients′ target delineation within 1-4 s of motion cycle and within 1 mm of motion amplitude, which exerts on effect upon the original position of probe.

Copula-Based Uncertainty Quantification (Copula-UQ) for Multi-Sensor Data in Structural Health Monitoring.

The problem of uncertainty quantification (UQ) for multi-sensor data is one of the main concerns in structural health monitoring (SHM). One important task is multivariate joint probability density function (PDF) modelling. Copula-based statistical inference has attracted significant attention due to the fact that it decouples inferences on the univariate marginal PDF of each random variable and the statistical dependence structure (called copula) among the random variables. This paper proposes the Copula-UQ, composing multivariate joint PDF modelling, inference on model class selection and parameter identification, and probabilistic prediction using incomplete information, for multi-sensor data measured from a SHM system. Multivariate joint PDF is modeled based on the univariate marginal PDFs and the copula. Inference is made by combing the idea of the inference functions for margins and the maximum likelihood estimate. Prediction on the PDF of the target variable, using the complete (from normal sensors) or incomplete information (due to missing data caused by sensor fault issue) of the predictor variable, are made based on the multivariate joint PDF. One example using simulated data and one example using temperature data of a multi-sensor of a monitored bridge are presented to illustrate the capability of the Copula-UQ in joint PDF modelling and target variable prediction.

[Expression Level and Target Gene Prediction of miR-181b in Patients with Chronic Lymphocytic Leukemia].

OBJECTIVE: To investigate the expression level of miR-181b in CD19+ B lymphocytes of patients with chronic lymphocytic leukemia (CLL), to analyze the relationship between its expression and the prognosis of CLL patients, and to predict the potential target gene of miR-181b in CLL by using bioinformatics. METHODS: Eight-four patients with CLL treated in People's Hospital of Xinjiang Uygur Autonomous Region from June 2013 to June 2018 were selected. and 20 healthy people were selected as control group. RNA was extracted from CD19+B lymphocytes of peripheral blood by magnetic bead sorting, the expression level of miR-181b was detected, and it's expression differences in different IPI groups were analyzed. The correlation between the expression level of miR-181b and PFS of CLL patients also was analyzed. miR-181b target genes were predicted by online database and literatures, and gene annotation analysis and relevant signal pathway analysis were performed for candidate target genes. RESULTS: The expression level of miR-181b in CLL patients was significantly lower than that in control group (P＜0.01); The expression level of miR-181b in the low-risk group was higher than that in high-risk group and extremely high-risk group (P＜0.05), but there was no statistical difference between low-risk group and medium-risk group (P=1.00). The expression level of miR-181b in medium-risk group was higher than that in high-risk group and extremely high-risk group (P＜0.05), but there was no difference between high-risk group and extremely high-risk group (P=1.00). ROC curve results showed that the area under the curve (AUC) was 0.792 (P＜0.01).When the expression level of miR-181b was at the threshold value of 0.279, it showed a better sensitivity (62.9%) and specificity (91.8%). Survival analysis results suggested that compared with the high expression group, the miR-181b low expression group had poor PFS (log rank: P=0.047). Prediction of miR-181b by using the starBase, targetscan and picTar database and its combination with literature reports indicated that CARD11, ZFP36L1, RUNX1, NR4A3, ATP1B1, PUM1 and PLAG1 related with blood diseases, and up-regulated CARD11 and ZFP36L1 participated in lymphoid tumor formation by promoting cell proliferation and inhibiting cell aging. CONCLUSION: The expression level of miR-181b in CLL group are significantly lower than that in the controls group, and the low expression of miR-181b relates with poor prognosis of CLL patients. Through bioinformatics prediction and combined with literature reports, it is speculated that CARD11 and ZFP36L1 as target genes of miR-181b may be participated in the occurrence and development of CLL. Further experiments are needed to verify this result.

[Application of CpG Oligodeoxynucleotide Immunostimulation in Chromosome Study of Chronic Lymphoblastic Leukemia].

OBJECTIVE: To explore the value of CpG-oligonucleotide(CpG-ODN) immunostimulatory method in chromosome culture of chronic lymphocytic leukemia (CLL) cells and to compare the differences between related studies at home and abroad, so as to improve the success rate of CLL karyotype culture and the detection rate of abnormal karyo-types. METHODS: Bone marrow samples from 82 CLL patients were collected and cultured with phytohemagglutinin (PHA), CpG-oligonucleotide plus interleukin-2 (CpG-ODN DSP30+IL-2) for 72 hours. Chromosomes were prepared and analyzed by conventional cytogenetics (CC). Meanwhile, D13S25, Rb1, ATM, p53 and CSP12 probes were used for interphase fluorescence in situ hybridization (iFISH) test. The differences of chromosome culture and iFISH test results between two cell stimulants were compared. RESULTS: The success rate of karyotype culture in PHA and CpG-ODN DSP30+IL-2 immunostimuli (analyzable mitotic t >20) was 90.2% (74 cases), 68.3% (56 cases) respectively, and the detection rate of abnormal karyotype was 13.5% (10 cases) and 46.4% (26 cases), respectively. The success rate of karyotype culture in PHA group was significantly higher than that in CpG-ODN DSP30+IL-2 group (P=0.01). The detection rate of abnormal karyotypes in CpG-ODN DSP30+IL-2 group was significantly higher than that in PHA group, and the difference was statistically significant (P=0.003). The detection rate of abnormal karyotypes in iFISH group was 74.4% (61 cases), which was significantly higher than that in CpG-ODN DSP30+IL-2 group (P=0.000). iFISH detection could verify the abnormalities detected by CC analysis. CONCLUSION: Application of CpG-ODN DSP30+IL-2 immunostimulation method in culture of CLL cells can enhance the detection rate of abnormal karyotypes, especially the detection of various translocations suggesting poor prognosis.

Inhibition of autophagic flux by cyclometalated iridium(iii) complexes through anion transportation.

Synthetic anion transporters that can interfere with the intracellular pH homeostasis are gaining increasing attention for tumor therapy, however, the biological mechanism of anion transporters remains to be explored. In this work, two phosphorescent cyclometalated Ir(iii) complexes containing 2-phenylpyridine (ppy) as the cyclometalated ligand, and 2,2'-biimidazole (H2biim, Ir1) or 2-(1H-imidazol-2-yl)pyridine (Hpyim, Ir2) as the ancillary ligands have been synthesized and characterized. Due to the protonation and deprotonation process of the N-H groups on H2biim and Hpyim, Ir1 and Ir2 display pH-dependent phosphorescence and can specifically image lysosomes. Both Ir1 and Ir2 can act as anion transporters mainly through the anion exchange mechanism with higher potency observed for Ir1. Mechanism investigation shows that Ir1 and Ir2 can induce caspase-independent cell death through reactive oxygen species (ROS) elevation. As Ir1 and Ir2 can alkalinize lysosomes through anion disturbance, they can inhibit autophagic flux. Our work provides a novel anticancer mechanism of metal complexes, which gives insights into the innovative structure-based design of new metallo-anticancer agents.

Anticancer Cyclometalated Iridium(III) Complexes with Planar Ligands: Mitochondrial DNA Damage and Metabolism Disturbance.

Emerging studies have shown that mitochondrial DNA (mtDNA) is a potential target for cancer therapy. Herein, six cyclometalated Ir(III) complexes Ir1-Ir6 containing a series of extended planar diimine ligands have been designed and assessed for their efficacy as anticancer agents. Ir1-Ir6 show much higher cytotoxicity than cisplatin and they can effectively localize to mitochondria. Among them, complexes Ir3 and Ir4 with dipyrido[3,2- a:2',3'- c]phenazine (dppz) ligands can bind to DNA tightly in vitro, intercalate to mtDNA in situ, and induce mtDNA damage. Ir3- and Ir4-impaired mitochondria exhibit decline of mitochondrial membrane potential, disability of adenosine triphosphate generation, disruption of mitochondrial energetic and metabolic status, which subsequently cause protective mitophagy, G0/G1 phase cell cycle arrest, and apoptosis. In vivo antitumor evaluations also show that Ir4 can inhibit tumor xenograft growth effectively. Overall, our work proves that targeting the mitochondrial genome may present an effective strategy to develop metal-based anticancer agents to overcome cisplatin resistance.

Application progress on metabolomics in nephrotoxicity of Chinese materia medica / 中草药

The nephrotoxicity of Chinese materia medica (CMM) can’t be ignored so that it needs effective monitor and prevention. Recently, the determination of biochemistry and pathology indexes is the most important means of research with low sensitivity and trauma. In recent years, metabolomics has shown broad prospects in CMM nephrotoxicity studies due to its systematic advantages, and also achieved remarkable success. However, large clinical sample studies are still needed to realize the clinical transformation of research results. Thus, the application of metabolomics in the toxicology, assessment biomarkers and mechanism of CMM nephrotoxicity are reviewed in this paper, in order to provide references for further research.

miR-93-5p Transferred by Exosomes Promotes the Proliferation of Esophageal Cancer Cells via Intercellular Communication by Targeting PTEN.

OBJECTIVE: To investigate the relationship between plasma miR-93-5p and the risk of esophageal cancer, as well as the influence of miR-93-5p on the biological function of esophageal cancer cells, exerted through exosomes. METHODS: The expression of plasma miR-93-5p in esophageal cancer patients and healthy controls was analysed by real-time quantitative PCR. The influence of miR-93-5p on the risk and prognosis of esophageal carcinoma was analyzed by conditional logistic regression and survival analysis. The effect of miR-93-5p on the biological function of recipient cells was investigated by establishing an in vitro donor cell co-culture model. The target gene of miR-93-5p was validated by luciferase reporter assay and Western Blotting. RESULTS: Upregulation of plasma miR-93-5p expression significantly increases the risk of esophageal cancer and is associated with poor prognosis. miR-93-5p transferred by exosomes promotes the proliferation of recipient esophageal cancer cells and affects the expression of PTEN and its downstream proteins p21 and cyclin D1. CONCLUSION: Our study provides a reference for the identification of biomarkers for the diagnosis and prognosis of esophageal cancer.

miR-93-5p Transferred by Exosomes Promotes the Proliferation of Esophageal Cancer Cells via Intercellular Communication by Targeting PTEN / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the relationship between plasma miR-93-5p and the risk of esophageal cancer, as well as the influence of miR-93-5p on the biological function of esophageal cancer cells, exerted through exosomes.</p><p><b>METHODS</b>The expression of plasma miR-93-5p in esophageal cancer patients and healthy controls was analysed by real-time quantitative PCR. The influence of miR-93-5p on the risk and prognosis of esophageal carcinoma was analyzed by conditional logistic regression and survival analysis. The effect of miR-93-5p on the biological function of recipient cells was investigated by establishing an in vitro donor cell co-culture model. The target gene of miR-93-5p was validated by luciferase reporter assay and Western Blotting.</p><p><b>RESULTS</b>Upregulation of plasma miR-93-5p expression significantly increases the risk of esophageal cancer and is associated with poor prognosis. miR-93-5p transferred by exosomes promotes the proliferation of recipient esophageal cancer cells and affects the expression of PTEN and its downstream proteins p21 and cyclin D1.</p><p><b>CONCLUSION</b>Our study provides a reference for the identification of biomarkers for the diagnosis and prognosis of esophageal cancer.</p>

Dual Functions of Cyclometalated Iridium(III) Complexes: Anti-Metastasis and Lysosome-Damaged Photodynamic Therapy.

Four phosphorescent cyclometalated iridium(III) complexes containing benzimidazole moiety have been designed and synthesized. These Ir(III) complexes can effectively inhibit several cancerous processes, including cell migration, invasion, colony formation, and angiogenesis. Interestingly, they show a much higher singlet oxygen quantum yield in an acidic solution than in a neutral solution. Upon irradiation at 425 nm with low energy (1.2 J cm-2), they can induce apoptosis through lysosomal damage, evaluation of reactive oxygen species level, and activation of caspase-3/7. The highest phototoxicity index is >476, with almost no dark cytotoxicity observed for Ir4. Ir4 can also inhibit tumor growth effectively in nude mice in vivo after photodynamic therapy. An in vitro assay against 70 kinases indicates that maternal embryonic leucine zipper kinase (MELK), PIK3CA, and AMPK are the possible molecular targets. The half maximal inhibitory concentration of Ir4 toward MELK is 1.27 µM. Our study demonstrates that these Ir(III) complexes are promising anticancer agents with dual functions, including metastasis inhibition and lysosome-damaged photodynamic therapy.

Effects of phenol on physicochemical properties and treatment performances of partial nitrifying granules in sequencing batch reactors.

This study attempts to investigate the effect of phenol on physicochemical properties and treatment performances of partial nitrifying granules (PNGs). Two sequencing batch reactors (SBRs) fed with synthetic ammonium wastewaters were operated in absence (R1) or presence (R2) of phenol. The PNGs in R1 maintained excellent partial nitrification performance and relatively stable physicochemical properties, and exhibited compact and regular shaped structure with a cocci-dominant surface. However, as phenol concentration was stepwise increased from 0 to 300 mg/L in R2, filamentous bacteria appeared and gradually dominated within granules, which in turn resulted in settleability deterioration. Most notably, granules in R2 got easier to agglomerate in the reactor walls and then been washed out with effluent, leading to significant biomass loss, frequent outflow pipe blockage, and eventual system failure. The extracellular polymeric substances (EPS) contents including proteins and polysaccharides in R2 reached 1.8 and 1.7 times of that in R1, respectively, indicating that the presence of phenol played an important role on EPS production. Removal efficiency of ammonium and phenol remained high, but dropped sharply when phenol concentration reached 300 mg/L. Moreover, the failed maintenance of partial nitrification was observed due to the revival of nitrite oxidizing bacteria (NOB) within granules after phenol exposure, which was confirmed by quantitative fluorescence in situ hybridization (FISH) analysis. Overall this study demonstrates that phenol had negative effects on PNGs, and pretreatment to eliminate phenolic substances is recommended when using PNGs for wastewater treatment.

Light-Up Mitophagy in Live Cells with Dual-Functional Theranostic Phosphorescent Iridium(III) Complexes.

Phosphorescent Ir(III) complexes are expected to be new multifunctional theranostic platforms that enable the integration of imaging capabilities and anticancer properties. Mitophagy is an important selective autophagic process that degrades dysfunctional mitochondria. Until now, the regulation of mitophagy is still poorly understood. Herein, we present two phosphorescent cyclometalated iridium(III) complexes (Ir1 and Ir2) that can accumulate in mitochondria and induce mitophagy. Because of their intrinsic phosphorescence, they can specially image mitochondria and track mitochondrial morphological alterations. Mechanism studies show that Ir1 and Ir2 induce mitophagy by depolarization of mitochondrial membrane potential, depletion of cellular ATP, perturbation in mitochondrial metabolic status, and induction of oxidative stress. Moreover, no sign of apoptosis is observed in Ir1- and Ir2-treated cells under the same conditions that an obvious mitophagic response is initiated. We demonstrate that Ir1 is a promising theranostic agent that can induce mitophagy and visualize changes in mitochondrial morphology simultaneously.

Tumor-targeted supramolecular nanoparticles self-assembled from a ruthenium-ß-cyclodextrin complex and an adamantane-functionalized peptide.

We report here a supramolecular strategy to assemble a cyclodextrin-functionalized anticancer Ru(ii) complex with an adamantane-appended tumor-targeting peptide into discrete and stable phosphorescent nanostructures that can induce cell death in integrin αvß3-rich tumor cells with high selectivity. This strategy presents new opportunities for the construction of tumor-targeting metallo-anticancer therapeutics.

Targeting cancer cell metabolism with mitochondria-immobilized phosphorescent cyclometalated iridium(iii) complexes.

Cancer cell metabolism is reprogrammed to sustain the high metabolic demands of cell proliferation. Recently, emerging studies have shown that mitochondrial metabolism is a potential target for cancer therapy. Herein, four mitochondria-targeted phosphorescent cyclometalated iridium(iii) complexes have been designed and synthesized. Complexes 2 and 4, containing reactive chloromethyl groups for mitochondrial fixation, show much higher cytotoxicity than complexes 1 and 3 without mitochondria-immobilization properties against the cancer cells screened. Further studies show that complexes 2 and 4 induce caspase-dependent apoptosis through mitochondrial damage, cellular ATP depletion, mitochondrial respiration inhibition and reactive oxygen species (ROS) elevation. The phosphorescence of complexes 2 and 4 can be utilized to monitor the perinuclear clustering of mitochondria in real time, which provides a reliable and convenient method for in situ monitoring of the therapeutic effect and gives hints for the investigation of anticancer mechanisms. Genome-wide transcriptional analysis shows that complex 2 exerts its anticancer activity through metabolism repression and multiple cell death signalling pathways. Our work provides a strategy for the construction of highly effective anticancer agents targeting mitochondrial metabolism through rational modification of phosphorescent iridium complexes.

Modulation of mesenchymal stem cells on autophagy in hippocampus of rats with hypoxic-ischemic brain damage / 上海交通大学学报（医学版）

Objective·To investigate the effect of mesenchymal stem cells (MSCs) on autophagy in hippocampus of neonatal rats with hypoxic-ischemic brain damage (HIBD). Methods·Western blotting was used to detect the expression levels of autophagy associated proteins Beclin1, LC3 Ⅱ , and p62 in the hippocampus of HIBD rats following MSCs transplantation and oxygen glucose deprivation (OGD)-injured primary neurons following MSCs seperated coculture. The learning-memory function in the HIBD rats after MSCs transplantation was tested by Morris water maze test. Transmission electron microscopy was also used to observe the number of autophagic neurons in OGD damaged neurons after coculture with MSCs. Results·The levels of Beclin1 and LC3 Ⅱ protein expressions were significantly increased at 12-24 h in the rat hippocampus following HIBD injury. MSCs transplantation statistically downregulated the autophagy level in the hippocampus, and obviously improved the learning-memory function of HIBD rats. Meanwhile, the levels of Beclin1 and LC3 Ⅱ protein expressions in the primary neurons in vitro were also induced by OGD for 12 h. MSCs seperated coculture significantly downregulated the autophagy level of hippocampal neurons by OGD injury, decreased the number of autophagosome in the OGD-injured neurons. Conclusion·MSCs may inhibit the autophagy of hippocampal neurons by partly regulating the damaged microenvironment to improve the learning and memory function of HIBD rats.

Ester-Modified Cyclometalated Iridium(III) Complexes as Mitochondria-Targeting Anticancer Agents.

Organometallic iridium complexes are potent anticancer candidates which act through different mechanisms from cisplatin-based chemotherapy regimens. Here, ten phosphorescent cyclometalated iridium(III) complexes containing 2,2'-bipyridine-4,4'-dicarboxylic acid and its diester derivatives as ligands are designed and synthesized. The modification by ester group, which can be hydrolysed by esterase, facilitates the adjustment of drug-like properties. The quantum yields and emission lifetimes are influenced by variation of the ester substituents on the Ir(III) complexes. The cytotoxicity of these Ir(III) complexes is correlated with the length of their ester groups. Among them, 4a and 4b are found to be highly active against a panel of cancer cells screened, including cisplatin-resistant cancer cells. Mechanism studies in vitro indicate that they undergo hydrolysis of ester bonds, accumulate in mitochondria, and induce a series of cell-death related events mediated by mitochondria. Furthermore, 4a and 4b can induce pro-death autophagy and apoptosis simultaneously. Our study indicates that ester modification is a simple and feasible strategy to enhance the anticancer potency of Ir(III) complexes.