Distinct Processing of lncRNAs Contributes to Non-conserved Functions in Stem Cells.

Long noncoding RNAs (lncRNAs) evolve more rapidly than mRNAs. Whether conserved lncRNAs undergo conserved processing, localization, and function remains unexplored. We report differing subcellular localization of lncRNAs in human and mouse embryonic stem cells (ESCs). A significantly higher fraction of lncRNAs is localized in the cytoplasm of hESCs than in mESCs. This turns out to be important for hESC pluripotency. FAST is a positionally conserved lncRNA but is not conserved in its processing and localization. In hESCs, cytoplasm-localized hFAST binds to the WD40 domain of the E3 ubiquitin ligase ß-TrCP and blocks its interaction with phosphorylated ß-catenin to prevent degradation, leading to activated WNT signaling, required for pluripotency. In contrast, mFast is nuclear retained in mESCs, and its processing is suppressed by the splicing factor PPIE, which is highly expressed in mESCs but not hESCs. These findings reveal that lncRNA processing and localization are previously under-appreciated contributors to the rapid evolution of function.

Altered nucleocytoplasmic export of adenosine-rich circRNAs by PABPC1 contributes to neuronal function.

Circular RNAs (circRNAs) are upregulated during neurogenesis. Where and how circRNAs are localized and what roles they play during this process have remained elusive. Comparing the nuclear and cytoplasmic circRNAs between H9 cells and H9-derived forebrain (FB) neurons, we identify that a subset of adenosine (A)-rich circRNAs are restricted in H9 nuclei but exported to cytosols upon differentiation. Such a subcellular relocation of circRNAs is modulated by the poly(A)-binding protein PABPC1. In the H9 nucleus, newly produced (A)-rich circRNAs are bound by PABPC1 and trapped by the nuclear basket protein TPR to prevent their export. Modulating (A)-rich motifs in circRNAs alters their subcellular localization, and introducing (A)-rich circRNAs in H9 cytosols results in mRNA translation suppression. Moreover, decreased nuclear PABPC1 upon neuronal differentiation enables the export of (A)-rich circRNAs, including circRTN4(2,3), which is required for neurite outgrowth. These findings uncover subcellular localization features of circRNAs, linking their processing and function during neurogenesis.

RNA circles with minimized immunogenicity as potent PKR inhibitors.

Exon back-splicing-generated circular RNAs, as a group, can suppress double-stranded RNA (dsRNA)-activated protein kinase R (PKR) in cells. We have sought to synthesize immunogenicity-free, short dsRNA-containing RNA circles as PKR inhibitors. Here, we report that RNA circles synthesized by permuted self-splicing thymidylate synthase (td) introns from T4 bacteriophage or by Anabaena pre-tRNA group I intron could induce an immune response. Autocatalytic splicing introduces ∼74 nt td or ∼186 nt Anabaena extraneous fragments that can distort the folding status of original circular RNAs or form structures themselves to provoke innate immune responses. In contrast, synthesized RNA circles produced by T4 RNA ligase without extraneous fragments exhibit minimized immunogenicity. Importantly, directly ligated circular RNAs that form short dsRNA regions efficiently suppress PKR activation 103- to 106-fold higher than reported chemical compounds C16 and 2-AP, highlighting the future use of circular RNAs as potent inhibitors for diseases related to PKR overreaction.

Using sno-lncRNAs as potential markers for Prader-Willi syndrome diagnosis.

The genetic disorder Prader-Willi syndrome (PWS) is mainly caused by the loss of multiple paternally expressed genes in chromosome 15q11-q13 (the PWS region). Early diagnosis of PWS is essential for timely treatment, leading to effectively easing some clinical symptoms. Molecular approaches for PWS diagnosis at the DNA level are available, but the diagnosis of PWS at the RNA level has been limited. Here, we show that a cluster of paternally transcribed snoRNA-ended long noncoding RNAs (sno-lncRNAs, sno-lncRNA1-5) derived from the SNORD116 locus in the PWS region can serve as diagnostic markers. In particular, quantification analysis has revealed that 6,000 copies of sno-lncRNA3 are present in 1 µL whole blood samples from non-PWS individuals. sno-lncRNA3 is absent in all examined whole blood samples of 8 PWS individuals compared to 42 non-PWS individuals and dried blood samples of 35 PWS individuals compared to 24 non-PWS individuals. Further developing a new CRISPR-MhdCas13c system for RNA detection with a sensitivity of 10 molecules per µL has ensured sno-lncRNA3 detection in non-PWS, but not PWS individuals. Together, we suggest that the absence of sno-lncRNA3 represents a potential marker for PWS diagnosis that can be detected by both RT-qPCR and CRISPR-MhdCas13c systems with only microlitre amount of blood samples. Such an RNA-based sensitive and convenient approach may facilitate the early detection of PWS.

[Childhood trauma and adolescent game addiction: the mediating effects of self-control]. / å„¿ç«¥æœŸåˆ›ä¼¤ä¸Žé’å°‘å¹´æ¸¸æˆæˆç˜¾çš„å ³ç³»ï¼šè‡ªæˆ‘æŽ§åˆ¶çš„ä¸­ä»‹ä½œç”¨.

OBJECTIVES: To investigate the association between childhood trauma and game addiction in adolescents, as well as the mediating effect of self-control. METHODS: A cross-sectional study was conducted using cluster random sampling. The participants were 2 664 adolescents from a senior high school in Henan Province. The research tools included a demographic data questionnaire, Childhood Trauma Questionnaire-Short Form, Self-Control Scale, and Game Addiction Scale for Adolescents. The Bootstrap method was used to test the parallel mediating effect, with the five dimensions of self-control as mediators. RESULTS: The prevalence of game addiction among the adolescents was 17.68% (471/2 664). There was a positive correlation between childhood trauma and game addiction scores (P<0.01), and a negative correlation between childhood trauma scores and each dimension of self-control (P<0.01). Moreover, all five dimensions of self-control were negatively correlated with game addiction scores (P<0.01) and acted as parallel mediators between childhood trauma and game addiction. The mediating effects of restraint from entertainment (accounting for 15.6% of the total effect) and resistance to temptation (accounting for 10.6% of the total effect) were stronger. CONCLUSIONS: Childhood trauma may increase the risk of game addiction by impairing adolescents' self-control abilities. The reduction of childhood trauma can cultivate self-control in adolescents and prevent the occurrence of game addiction.

[Association between maternal job burnout and adolescent depression: the chain mediating effect of maternal depression and parenting style]. / æ¯äº²èŒä¸šå€¦æ€ å’Œé’å°‘å¹´æŠ‘éƒçš„å ³ç³»ï¼šæ¯äº²æŠ‘éƒå’Œæ•™å »æ–¹å¼çš„é“¾å¼ä¸­ä»‹ä½œç”¨.

OBJECTIVES: To investigate the association between maternal job burnout and adolescent depression and the mediating effect of maternal depression and parenting style. METHODS: A cross-sectional study was conducted. The cluster random sampling method was used to select 2 572 adolescents from 7 middle schools in Shanghai, China, from April to May, 2021. A survey was performed for these adolescents and their mothers. The research tools included a general information questionnaire, Maslach Burnout Inventory-General Survey, Center for Epidemiologic Studies Depression Scale, short-form of Egna Minnen av Barndoms Uppfostran, and Children's Depression Inventory. A structural equation model was established, and the Bootstrap method was used to investigate the mediating effect. RESULTS: The detection rate of depressive symptoms was 12.71% (327/2 572) among the adolescents. The scores of maternal job burnout, maternal depression, and negative parenting style were positively correlated with the score of adolescent depression (P<0.05), and the score of positive parenting style was negatively correlated with the score of adolescent depression (P<0.05). Maternal depression and parenting style played a mediating role between maternal job burnout and adolescent depression, including the individual mediating effect of maternal depression, the individual mediating effect of positive parenting style, and the chain mediating effect of maternal depression-negative/positive parenting style. CONCLUSIONS: Maternal job burnout may affect adolescent depression through the mediating effect of depression, parenting style, and depression-parenting style, suggesting that the symptoms of adolescent depression can be reduced by alleviating maternal job burnout, improving maternal depression, increasing positive parenting behaviors, and reducing negative parenting behaviors.

[The influence of family structure on depression and anxiety symptoms in adolescents: the mediating role of emotional neglect]. / å®¶åº­ç»“æž„å¯¹é’å°‘å¹´æŠ‘éƒå’Œç„¦è™‘ç—‡çŠ¶çš„å½±å“ï¼šæƒ æ„Ÿå¿½è§†çš„ä¸­ä»‹ä½œç”¨.

OBJECTIVES: To study the influence of family structure on depression and anxiety symptoms in adolescents and its mechanism. METHODS: The cluster sampling method was used to select the students from seven middle schools in Shanghai, China. An online questionnaire survey was conducted using a self-made general status questionnaire, Childhood Trauma Questionnaire, Children's Depression Inventory, and Screen for Child Anxiety Related Emotional Disorders. The methods including one-way analysis of variance, chi-square test, binary logistic regression analysis, and mediating effect analysis were used to evaluate depression and anxiety symptoms in adolescents and the difference in childhood trauma and its mediating effect. RESULTS: Compared with the adolescents from nuclear families, the adolescents from three-generation lineal families had a lower risk of depression symptoms (OR=0.794, 95%CI: 0.649-0.972, P<0.05), while those from host families had a higher risk of depression symptoms (OR=4.548, 95%CI: 1.113-18.580, P<0.05). The adolescents from inter-generational families and host families had a significantly higher score on the Childhood Trauma Questionnaire subscale of emotional neglect (P<0.05). Emotional neglect played a mediating role in the influence of inter-generational families and host families on depression symptoms in adolescents. CONCLUSIONS: Parents and grandparents have a certain positive effect in family structures. Separation from parents may make adolescents perceive more emotional neglect, which may increase the occurrence of depression symptoms.

Pioglitazone Metformin Complex Improves Polycystic Ovary Syndrome Comorbid Psychological Distress via Inhibiting NLRP3 Inflammasome Activation: A Prospective Clinical Study.

OBJECTIVE: This study aimed at investigating the therapeutic effect and mechanism of pioglitazone metformin complex preparation (PM) in polycystic ovary syndrome (PCOS) comorbid psychological distress. METHODS: Seventy-five patients with PCOS comorbid psychological distress were randomly allocated into the PM, metformin, and placebo groups. The primary efficacy measure was the change from baseline to week 12 on the Symptom Checklist 90-R (SCL-90-R) scores. NLRP3 inflammasome, IL-1ß, IL-6, TNF-α, and biochemical parameters were determined at baseline and at week 12. The participants were required to meet the criteria for PCOS (Rotterdam, NIH) and psychological distress (any factor scores of SCL - 90 - R > 2). RESULTS: The participants had significantly high scores on the SCL-90-R scales of anxiety and depression. PM significantly decreased anxiety and depression symptom severity (from 2.31 ± 0.75 to 1.65 ± 0.38, p < 0.001, and from 2.08 ± 0.74 to 1.61 ± 0.46, p = 0.010, at week 12, respectively). PM significantly decreased the expression of NRPL3 and caspase-1. Patients in the PM group experienced a significant reduction in IL-1ß (from 98.42 ± 14.38 to 71.76 ± 13.66, p = 0.02), IL-6 (from 87.51 ± 8.74 to 71.98 ± 15.87, p = 0.02), and TNF-α (from 395.33 ± 88.55 to 281.98 ± 85.69, p = 0.04). PM was superior to metformin in reducing total testosterone (2.24 ± 0.74 versus 3.06 ± 0.83, p = 0.024, at week 12). CONCLUSIONS: This study is the first to reveal that PM alleviates psychological distress via inhibiting NLRP3 inflammasome and improves several markers, including total testosterone.

[Association of suicidal ideation with family environment and psychological resilience in adolescents].

OBJECTIVE: To study the association of suicidal ideation with family environment and psychological resilience in adolescents. METHODS: Cluster sampling was used to perform an investigation among 3 230 junior and senior high school students in Xinxiang of Henan Province, China December 2014. A general social information questionnaire, 11-Item Kutcher Adolescent Depression Scale(KADS-11), Family Environment Scale-Chinese Version (FES-CV) and Connor-Davidson Resilience Scale (CD-RISC; Chinese version ) were used for evaluation. A multivariate logistic regression analysis and a case-control study were used to investigate the association of suicidal ideation with family environment and psychological resilience in adolescents. RESULTS: A total of 2 960 usable questionnaires were received. Among the 2 960 adolescents, 247 (8.50%) had suicidal ideation (98 boys and 149 girls). The multivariate logistic regression analysis showed that after adjustment for age and sex, single-parent/remarried family was associated with an increased risk of suicidal ideation (OR=2.655). Suicidal ideation in boys was negatively correlated with family cohesion (OR=0.750, P<0.001) and organization (OR=0.855, P=0.036) and was positively correlated with family conflict (OR=1.159, P=0.017). Suicidal ideation in girls were negatively correlated with family cohesion (OR=0.771, P<0.001), emotional expression (OR=0.815, P=0.001) and intellectual-cultural orientation (OR=0.915, P=0.037). The adolescents with suicidal ideation had a significantly lower total score of psychological resilience than those without suicidal ideation (P<0.05). Compared with those without suicidal ideation, the adolescents with suicidal ideation had significantly lower scores on 4 factors of the CD-RISC (ability, tolerance of negative emotions, acceptance of changes and control) (P<0.05). CONCLUSIONS: Family cohesion is a protective factor against suicidal ideation in adolescents. Family organization in boys and family emotional expression in girls are associated with a decreased risk of suicidal ideation. Enhanced psychological resilience may help to reduce the incidence of suicide ideation in adolescents.

Therapeutic application of circular RNA aptamers in a mouse model of psoriasis.

Efforts to advance RNA aptamers as a new therapeutic modality have been limited by their susceptibility to degradation and immunogenicity. In a previous study, we demonstrated synthesized short double-stranded region-containing circular RNAs (ds-cRNAs) with minimal immunogenicity targeted to dsRNA-activated protein kinase R (PKR). Here we test the therapeutic potential of ds-cRNAs in a mouse model of imiquimod-induced psoriasis. We find that genetic supplementation of ds-cRNAs leads to inhibition of PKR, resulting in alleviation of downstream interferon-α and dsRNA signals and attenuation of psoriasis phenotypes. Delivery of ds-cRNAs by lipid nanoparticles to the spleen attenuates PKR activity in examined splenocytes, resulting in reduced epidermal thickness. These findings suggest that ds-cRNAs represent a promising approach to mitigate excessive PKR activation for therapeutic purposes.

Bone marrow-derived mesenchymal stem cell-conditioned medium ameliorates diabetic foot ulcers in rats.

OBJECTIVES: This study aimed to explore the effects of bone marrow-derived Mesenchymal Stem Cell-Conditioned Medium (MSC-CM) treating diabetic foot ulcers in rats. METHODS: Models of T2DM rats were induced by a high-fat diet and intraperitoneal injection of STZ in SD rats. Models of Diabetic Foot Ulcers (DFUs) were made by operation on hind limbs in diabetic rats. Rats were divided into four groups (n = 6 for each group), i.e., Normal Control group (NC), Diabetes Control group (DM-C), MSC-CM group and Mesenchymal Stem Cells group (MSCs). MSC-CM group was treated with an injection of conditioned medium derived from preconditioned rats' bone marrow MSCs around ulcers. MSCs group were treated with an injection of rats' bone marrow MSCs. The other two groups were treated with an injection of PBS. After the treatment, wound closure, re-epithelialization (thickness of the stratum granulosums of the skin, by H&E staining), cell proliferation (Ki67, by IHC), angiogenesis (CD31, by IFC), autophagy (LC3B, by IFC and WB; autolysosome, by EM) and pyroptosis (IL-1ß, NLRP3, Caspase-1, GSDMD and GSDMD-N, by WB) in ulcers were evaluated. RESULTS: After the treatment wound area rate, IL-1ß by ELISA, and IL-1ß, Caspase-1, GSDMD and GSDMD-N by WB of MSC-CM group were less than those of DM group. The thickness of the stratum granulosums of the skin, proliferation index of Ki67, mean optic density of CD31 and LC3B by IFC, and LC3B by WB of MSC-CM group were more than those of DM group. The present analysis demonstrated that the injection of MSC-CM into rats with DFUs enhanced the wound-healing process by accelerating wound closure, promoting cell proliferation and angiogenesis, enhancing cell autophagy, and reducing cell pyroptosis in ulcers. CONCLUSIONS: Studies conducted indicate that MSC-CM administration could be a novel cell-free therapeutic approach to treat DFUs accelerating the wound healing process and avoiding the risk of living cells therapy.

[Preliminary study on variations and neural generators of error-related negativity in first episode schizophrenics].

OBJECTIVE: To explore the variations and their activated brain areas of error-related negativity (ERN) in first episode schizophrenics. METHODS: ERN was tested by an ERP device and their activated brain areas were compared in 58 first episode schizophrenics (FES) and 62 normal controls (NC) from March 2010 to February 2011. RESULTS: (1) The ERN latencies in the FES group were significantly longer on Cz (58 ± 14 ms), Fz (60 ± 11 ms), C3 (57 ± 17 ms) and C4 (60 ± 13 ms) electrodes compared with those in the NC group (49 ± 13 ms, 47 ± 13 ms, 50 ± 14 ms, 51 ± 12 ms). And the ERN amplitudes were significantly lower than those in the controls in Cz (5.0 ± 2.8 µV; 7.5 ± 3.1 µV, P < 0.01), C3 (5.5 ± 4.0 µV; 8.0 ± 3.7 µV, P < 0.01), Fz (5.0 ± 3.1 µV; 7.7 ± 3.8 µV, P < 0.01) and Pz (4.5 ± 3.3 µV: 7.5 ± 3.0 µV, P < 0.01) electrodes.(2) The variations of ERN latencies and amplitudes showed an insignificant correlation with the positive symptom scores and total scores of PANSS. (3) The activation levels of insula, superior temporal gyrus, middle temporal gyrus and inferior parietal lobule were obviously lower in the FES group than those in the NC group. CONCLUSION: The anomalies of ERN latencies and amplitudes in first episode schizophrenics may reflect the deficient error-monitoring functions. Further studies are warranted. And such brain areas as insular may contribute pathogenically to the dysfunctions of error-monitoring in schizophrenics.

Network pharmacology-based exploration of therapeutic mechanism of Liu-Yu-Tang in atypical antipsychotic drug-induced metabolic syndrome.

BACKGROUND: Metabolic syndrome (MetS) is prevalent in patients receiving atypical antipsychotic drugs (AADs), but there are few effective interventions. The Traditional Chinese herbal decoction Liu-Yu-Tang (LYT) has achieved clinical improvement for AAD-induced MetS, but its pharmacological mechanism remains unclear. METHOD: A network pharmacology-based method was utilized in this study. First, the TCMSP and SwissTargetPrediction database were used to acquire plasma-absorbed components and putative targets of LYT, respectively. Second, an interaction network between shared targets of LYT and MetS was constructed using STRING online tool. Topological analyses were performed to extract hub gene targets. Finally, we did a pathway analysis of gene targets using the Kyoto Encyclopedia of Genes and Genomes (KEGG) to find biological pathways of LYT. RESULTS: We obtained 655 putative targets of LYT, 434 known targets of AADs, and 1577 MetS-related gene targets. There are 232 shared targets between LYT and MetS. Interaction network construction and topological analysis yielded 60 hub targets, of which 18 were major hub targets, among which IL-6, IL-8, TNF, PI3K, MAPK, and NF-κB (RELA) are the most important in LYT's treatment of AAD-induced MetS. Pathway enrichment analysis revealed a statistically high significance of the AGE-RAGE signaling pathway in diabetic complications, lipid and atherosclerosis and the insulin resistance pathway. CONCLUSIONS: LYT may control activities of the pro-inflammatory cytokines IL-6, IL-8, TNF and the important signal transduction molecules PI3K, MAPKs, and NF-κB (RELA), regulating metabolic disturbance-related pathways like the AGE-RAGE signaling pathway in diabetic complications, lipid and atherosclerosis, and the insulin resistance pathway, generating therapeutic effects for AAD-induced MetS.

SNX29, a new susceptibility gene shared with major mental disorders in Han Chinese population.

OBJECTIVES: Environmental and genetic factors play important roles in the development of schizophrenia (SCZ), bipolar disorder (BPD) or major depressive disorder (MDD). Some risk loci are identified with shared genetic effects on major psychiatric disorders. To investigate whether SNX29 gene played a significant role in these psychiatric disorders in the Han Chinese population. METHODS: We focussed on 11 single-nucleotide polymorphisms (SNPs) harbouring SNX29 gene and carried out case-control studies in patients with SCZ (n = 1248), BPD (n = 1344), or MDD (n = 1056), and 1248 healthy controls (HC) recruited from the Han Chinese population. We constructed weighted gene co-expression network analysis (WGCNA) and extracted significant modules by R package. RESULTS: We found that rs3743592 was significantly associated with MDD and rs6498263 with BPD in both allele and genotype distributions. Before correction, rs3743592 showed allelic and genotypic significance with SCZ, rs6498263 showed allelic significance with SCZ. WGCNA identified top 10 modules of co-expressed genes. Gene Ontology (GO) and pathway analysis were used to examine the functions of SNX29, which revealed that SNX29 was involved in the regulation of a number of biological processes, such as TGF-beta, ErbB, and Wnt signalling pathway, etc. CONCLUSIONS: Our results supported common risk factors in SNX29 might share among these three mental disorders in the Han Chinese population.

[Association of cyclic adenosine monophosphate response element-binding protein gene and major depressive disorder].

OBJECTIVE: To investigate the association between single nucleotide polymorphisms (SNPs) in cyclic adenosine monophosphate response element-binding protein(CREB1) gene and major depressive disorder (MDD). METHODS: We recruited 105 parent-offspring trios of Chinese descent, extracted whole blood genomic DNA, and genotyped the SNPs in rs10932201 and rs6740584 loci. Single-marker transmission disequilibrium test (TDT), pairwise SNP linkage disequilibrium(LD) and haplotype-based TDT were performed. RESULTS: No significant association with MDD was observed for SNPs rs10932201 and rs6740584 (P=0.1004 and P=0.4986). However, there was strong positive association between the rs10932201-rs6740584 haplotype and MDD (P=0.00003241), and both haplotypes of A-C and A-T were significantly associated with MDD (P=0.020 and P=0.00022). CONCLUSION: The rs10932201-rs6740584 haplotype of the CREB1 gene may play an important role in the pathogenesis of MDD.

[N400 changes elicited by Chinese sentences in first episode schizophrenia].

OBJECTIVE: To explore N400 changes elicited by Chinese sentences ending with matching (congruent) or mismatching (incongruent) words in first episode schizophrenia. METHODS: ERP (event-related potentials) component N400 were recorded by an ERP device in 56 first episode schizophrenia (FES) and 62 normal controls (NC) according to a paradigm of Chinese sentences ending with matching or mismatching words. RESULTS: (1) Latencies: compared with NC, FES showed prolonged N400 latencies in five areas at pre-treatment: in Cz. The latencies were (358 ms ± 32 ms vs 394 ms ± 45 ms, P < 0.01) in congruent and (410 ms ± 29 ms vs 446 ms ± 35 ms, P < 0.01) in incongruent situation. And so did in Fz, Pz, C3 and C4; (2) amplitudes: compared with NC, FES also showed smaller N400 amplitudes in five areas at pre-treatment. The amplitudes were (8.6 µV ± 5.1 µV vs 5.2 µV ± 4.6 µV, P < 0.01) in congruent and (13.4 µV ± 6.7 µV vs 8.5 µV ± 5.9 µV, P < 0.01) in incongruent situation. And so did in Fz, Pz, C3 and C4; (3) the prolonged N400 latencies and decreased amplitudes were negatively correlated with the patients' positive scale and total scale of PANSS. CONCLUSION: With clear priming effect in first episode schizophrenia, Chinese sentences are suitable stimuli in N400 experiment. They may be used for further study of neural mechanism and early diagnosis of schizophrenia.

[Functional improvement of patients with progressive muscular dystrophy by bone marrow and umbilical cord blood mesenchymal stem cell transplantations].

OBJECTIVE: To investigate the feasibility of employing double transplantations of autologous bone marrow mesenchymal stem cells (BMSC) and umbilical cord mesenchymal stem cells (UMSC) in the treatment of progressive muscular dystrophy (PMD). METHODS: A total of 82 cases were treated by the double transplantations of BMSC and CB-MSC. They were diagnosed by clinical manifestations, CK, LDH, genetic analysis, electromyography, MRI and pathologic examination of biopsied muscle specimens from July 2007 to July 2008. Control group was self-made at before and after treatment and cases were followed up for 3 - 12 months. treatment method: Eighty-two patients underwent the double transplantations of bone mesenchymal stem cell (BMSC) and human umbilical cord blood MSC (CB-MSC). (1) BMSC: 80 - 150 ml bone marrow sample was collected through a puncture at bilateral posterior superior iliac spine. Ficoll density gradient centrifuge was employed to separate individual monocyte for induced differentiation. (2) CB-MSC: 80 - 160 ml umbilical cord blood was harvested and processed likewise as above. (3) Stem cell transplantation: Both BMSC and CB-MSC were collected and prepared into 1 x 10(8)/ml and 1 x 10(7)/ml cell suspension respectively. They were transplanted in divided does into the extremity muscle and vein. The clinical and laboratory parameters were monitored at 3, 6, 9 and 12 months. RESULTS: It was found that 31 cases (37.8%) obtained a remarkable efficacy, 37 cases (45.1%) were effective and 14 cases (17.1%) had no change. Total effective rate was 82.9%. Seventy patients (85.4%) felt limbs warmly, appetite improved, gained weight, had better appetite and action were nimble. Activity of daily living scale (ADL) in 72 patients (87.8%) increased as compared with pre-treatment (P < 0.01). LDH decreased at post-treatment [(475 +/- 223) u/L vs (410 +/- 216) u/L, P < 0.05, t = 6.650]. Creatine kinase [(2952 +/- 2259) u/L vs (2841 +/- 2092) u/L, P = 0.223, t = 1.094] and creatine [(26 +/- 12) micromol/L vs (25 +/- 11) micromol/L, P = 0.306, t = 1.029] decreased slightly. Adherence to therapy among Children and no adverse reaction was reported during the course of treatment. CONCLUSION: The double transplantation of BMSC and CB-MSC is convenient, safe and effective in the treatment of progressive muscular dystrophy and can be considered as a new therapy of PMD. MSC represents a possible tool of cellular therapeutics for PMD.

TiO2 nanocrystals with the {001} and {101} facets co-exposed with MIL-100(Fe): an egg-like composite nanomaterial for efficient visible light-driven photocatalysis.

The exposure of a specific crystal face to a specific composition or a suitable carrier composition with synergistic effects can effectively improve the photocatalytic activity of the material and enhance its practical value. For choosing an ideal carrier, the primary factor is a large specific surface area. Herein, by using MIL-100(Fe) as the carrier, an egg-like TiO2/MIL-100(Fe) composite was successfully prepared, for the first time, via a facile two-pot hydrothermal method. XRD, SEM, TEM and other characterization methods showed that when the molar ratio of Ti : Fe was 0.3 : 1, the morphology of the TiO2/MIL-100(Fe) composite was completely egg-like. The TEM results showed that the {001} and {101} facets of TiO2 in the TiO2/MIL-100(Fe) composite were co-exposed. The BET results showed that the TiO2/MIL-100(Fe) composite had a large specific surface area and pore size. The larger pore size provided an effective channel for the photocatalytic degradation of MB and the interfacial effect of TiO2 and MIL-100(Fe). The separation efficiency of the photogenerated electron-hole pairs was effectively improved. The efficiency of 30% TiO2/MIL-100(Fe) in the photocatalytic degradation of MB reached 99.02% in 30 min under visible light. All these findings showed that the composite of the effectively charge-separated photocatalytic semiconductor and the porous MOF with a high specific surface area had a high potential application value for the photocatalytic degradation of organic pollutants.

Network pharmacology-based identification for therapeutic mechanism of Ling-Gui-Zhu-Gan decoction in the metabolic syndrome induced by antipsychotic drugs.

BACKGROUND: The metabolic syndrome (MetS) is a common side effect of second-generation antipsychotic drugs (SGAs), leading to poor prognosis in patients with mental illness. The traditional Chinese herbal formula Ling-Gui-Zhu-Gan decoction (LGZGD) is a clinically validated remedy for SGAs-induced MetS, but its underlying mechanism remains unclear. METHODS: A network pharmacology-based analysis was performed to explore predicted plasma-absorbed components, putative therapeutic targets, and main pathways involved in LGZGD bioactivity. We constructed a target interaction network between the predicted targets of LGZGD and the known targets of MetS, after which we extracted major hubs using topological analysis. Thereafter, the maximum value of "edge betweenness" of all interactions was defined as a bottleneck, which suggested its importance in connecting all targets in the network. Finally, a pathway enrichment analysis of major hubs was used to reveal the biological functions of LGZGD. RESULTS: This approach identified 120 compounds and 361 candidate targets of LGZGD. According to the data generated in this study, the interaction between JUN and APOA1 plays a vital role in the treatment of SGAs-induced MetS using LGZGD. Interestingly, JUN was a putative target of LGZGD and APOA1 is one of the known targets of both MetS and SGAs (olanzapine and clozapine). LGZGD was significantly associated with several pathways including PI3K-Akt signaling, insulin resistance, and MAPK signaling pathway. CONCLUSIONS: LGZGD might inhibit JUN and thereby increases the expression of APOA1 to maintain metabolic homeostasis via some vital pathways.