Protective effect of melatonin against metabolic disorders and neuropsychiatric injuries in type 2 diabetes mellitus mice.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by hyperglycemia and progressive cognitive dysfunction, and our clinical investigation revealed that the plasma concentration of melatonin (Mlt) decreased and was closely related to cognition in T2DM patients. However, although many studies have suggested that Mlt has a certain protective effect on glucose and lipid metabolism disorders and neuropsychiatric injury, the underlying mechanism of Mlt against T2DM-related metabolic and cognitive impairments remains unclear. PURPOSE: The aim of the present study was to investigate the therapeutic effect of Mlt on metabolic disorders and Alzheimer's disease (AD)-like neuropsychiatric injuries in T2DM mice and to explore the possible underlying molecular mechanism involved. METHODS: A T2DM mouse model was established by a combination of a high-fat diet (HFD) and streptozotocin (STZ, 100 mg/kg, i.p.), and Mlt (5, 10 or 20 mg/kg) was intragastrically administered for six consecutive weeks. The serum levels of glycolipid metabolism indicators were measured, behavioral performance was tested, and the protein expression of key molecules involved in the regulation of synaptic plasticity, circadian rhythms, and neuroinflammation in the hippocampus was detected. Moreover, the fluorescence intensities of glial fibrillary acidic protein (GFAP), ionized calcium binding adapter molecule 1 (IBA-1), amyloid ß-protein (Aß) and phosphorylated Tau (p-Tau) in the hippocampus were also observed. RESULTS: Treatment with Mlt not only improved T2DM-related metabolic disorders, as indicated by increased serum concentrations of fasting blood glucose (FBG), glycosylated hemoglobin (HbAlc), insulin (INS), total cholesterol (TC) and triglyceride (TG), improved glucose tolerance and liver and pancreas function but also alleviated AD-like neuropsychiatric injuries in a HFD/STZ-induced mouse model, as indicated by decreased immobility time in the tail suspension test (TST) and forced swimming test (FST), increased preference indices of novel objects or novel arms in the novel object recognition test (NOR) and Y-maze test (Y-maze), and improved platform positioning capability in the Morris water maze (MWM) test. Moreover, treatment with Mlt also improved the hyperactivation of astrocytes and microglia in the hippocampus of mice, accompanied by reduced expression of interleukin 1ß (IL-1ß), interleukin 6 (IL-6), tumor necrosis factor (TNF-α), Aß, and p-Tau and increased expression of brain-derived neurotrophic factor (BDNF), Synapsin I, Synaptotagmin I, melatonin receptor 1B (MT1B), brain muscle arnt-like protein 1 (Bmal1), circadian locomotor output cycles kaput (Clock), period 2 (Per2), and cryptochrome 2 (Cry2). CONCLUSION: Mlt alleviated T2DM-related metabolic disorders and AD-like neuropsychiatric injuries in a HFD/STZ-induced mouse model, possibly through a mechanism involving the regulation of glial activation and associated neuroinflammation and the balancing of synaptic plasticity and circadian rhythms in the hippocampus.

Dynamic Changes in Neuroglial Reaction and Tissue Repair after Photothrombotic Stroke in Neonatal Mouse.

Perinatal and neonatal ischemic stroke is a significant cause of cognitive and behavioral impairments. Further research is needed to support models of neonatal ischemic stroke and advance our understanding of the mechanisms of infarction formation following such strokes. We used two different levels of photothrombotic stroke (PTS) models to assess stroke outcomes in neonatal mice. We measured brain damage, dynamic changes in glial cells, and neuronal expression at various time points within two weeks following ischemic injury. Our results from 2,3,5-Triphenyltetrazolium chloride (TTC) staining and immunofluorescence staining showed that in the severe group, a dense border of astrocytes and microglia was observed within 3 days post infarct. This ultimately resulted in the formation of a permanent cortical cavity, accompanied by neuronal loss in the surrounding tissues. In the mild group, a relatively sparse arrangement of glial borders was observed 7 days post infarct. This was accompanied by intact cortical tissue and the restoration of viability in the brain tissue beyond the glial boundary. Additionally, neonatal ischemic injury leads to the altered expression of key molecules such as Aldh1L1 and Olig2 in immature astrocytes. In conclusion, we demonstrated the dynamic changes in glial cells and neuronal expression following different degrees of ischemic injury in a mouse model of PTS. These findings provide new insights for studying the cellular and molecular mechanisms underlying neuroprotection and neural regeneration after neonatal ischemic injury.

Prevalence and risk factors of tuberculosis among people living with HIV/AIDS in China: a systematic review and meta-analysis.

OBJECTIVE: To estimate the prevalence and risk factors associated with tuberculosis (TB) among people living with human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) in China. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. After the literature was screened based on the inclusion and exclusion criteria, STATA® version 17.0 software was used for the meta-analysis. The heterogeneity among study data was assessed using I2 statistics. Subgroup analysis and meta-regressions were performed to further explore the source of heterogeneity. RESULTS: A total of 5241 studies were retrieved. Of these, 44 studies were found to be eligible. The pooled prevalence of HIV/TB co-infection was 6.0%. The risk factors for HIV/TB co-infection included a low CD4+ T cell count, smoking, intravenous drug use and several other sociodemographic and clinical factors. Bacillus Calmette-Guérin (BCG) vaccination history was a protective factor. CONCLUSION: A high prevalence of TB was observed among people living with HIV/AIDS in China. Low CD4+ T cell count, smoking, and intravenous drug use were the primary risk factors for HIV/TB co-infection, whereas BCG vaccination history was a protective factor. Checking for TB should be prioritized in HIV screening and healthcare access. SYSTEMATIC REVIEW REGISTRATION: Registered on PROSPERO, Identifier: CRD42022297754.

Krüppel-like factor 7 deficiency disrupts corpus callosum development and neuronal migration in the developing mouse cerebral cortex.

Krüppel-like Factor 7 (KLF7) is a zinc finger transcription factor that has a critical role in cellular differentiation, tumorigenesis, and regeneration. Mutations in Klf7 are associated with autism spectrum disorder, which is characterized by neurodevelopmental delay and intellectual disability. Here we show that KLF7 regulates neurogenesis and neuronal migration during mouse cortical development. Conditional depletion of KLF7 in neural progenitor cells resulted in agenesis of the corpus callosum, defects in neurogenesis, and impaired neuronal migration in the neocortex. Transcriptomic profiling analysis indicated that KLF7 regulates a cohort of genes involved in neuronal differentiation and migration, including p21 and Rac3. These findings provide insights into our understanding of the potential mechanisms underlying neurological defects associated with Klf7 mutations.

Role of Bmal1 in Type 2 Diabetes Mellitus-Related Glycolipid Metabolic Disorder and Neuropsychiatric Injury: Involved in the Regulation of Synaptic Plasticity and Circadian Rhythms.

Increasing data suggest a crucial role of circadian rhythm in regulating metabolic and neurological diseases, and Bmal1 is regarded as a key regulator of circadian transcription. The aim of this study is to investigate the role of Bmal1 in the disruption of circadian rhythm and neuropsychiatric injuries in type 2 diabetes mellitus (T2DM). A T2DM model was induced by the combination of high-fat-diet (HFD) and streptozotocin (STZ) in vivo or HT-22 cells challenged with palmitic-acid (PA) in vitro. The glucolipid metabolism indicators, behavioral performance, and expression of synaptic plasticity proteins and circadian rhythm-related proteins were detected. These changes were also observed after interference of Bmal1 expression via overexpressed plasmid or small interfering RNAs in vitro. The results showed that HFD/STZ could induce T2DM-like glycolipid metabolic turmoil and abnormal neuropsychiatric behaviors in mice, as indicated by the increased concentrations of fasting blood-glucose (FBG), HbA1c and lipids, the impaired glucose tolerance, and the decreased preference index of novel object or novel arm in the novel object recognition test (NOR) and Y-maze test (Y-maze). Consistently, the protein expression of synaptic plasticity proteins and circadian rhythm-related proteins and the positive fluorescence intensity of MT1B and Bmal1 were decreased in the hippocampus of HFD/STZ-induced mice or PA-challenged HT-22 cells. Furthermore, overexpression of Bmal1 could improve the PA-induced lipid metabolic dysfunction and increase the decreased expressions of synaptic plasticity proteins and circadian rhythm-related proteins, and vice versa. These results suggested a crucial role of Bmal1 in T2DM-related glycolipid metabolic disorder and neuropsychiatric injury, which mechanism might be involved in the regulation of synaptic plasticity and circadian rhythms.

Conflict or Collaboration-The Impact of Knowledge Endowment Heterogeneity on Remix in Open Collaborative Communities.

With the emergence of online open platforms and communities, remix has drawn much attention as an essential source of innovation whereby the knowledge endowment of online community users plays a crucial role. This study constructs a structural equation model to explore the impact of user knowledge endowment heterogeneity on remix through the mediating effect of their collaborative psychology. In this empirical study, we collected 25,032 pieces of data from Thingiverse (a 3D printing community) users and their published designs. The findings are as follows. Explicit knowledge endowment heterogeneity has a positive impact on the quantity of remix but a negative impact on its quality. Likewise, the implicit knowledge endowment heterogeneity positively affects the quantity of remix but has no significant effect on its quality. Users' conflicting psychology plays a mediating role between knowledge endowment heterogeneity and remix, while their collaborative psychology negatively mediates merely between explicit knowledge endowment heterogeneity and remix quality. By unraveling the relationship between user knowledge endowment heterogeneity, collaborative psychology, and remix, this study is significant in understanding users' remix process in open collaborative communities and illuminating their psychological mechanism in this process.

Resveratrol ameliorates learning and memory impairments induced by bilateral hippocampal injection of streptozotocin in mice.

Resveratrol (RES) is a polyphenol with diverse beneficial pharmacological activities, and our previous results have demonstrated its neuroprotective potential. The purpose of this study was to investigate the therapeutic effect of RES in Alzheimer's disease (AD)-like behavioral dysfunction induced by streptozotocin (STZ) and explore it's potential mechanism of action. STZ was microinjected bilaterally into the dorsal hippocampus of C57BL/6J mice at a dose of 3 mg/kg, and RES was administered intragastrically at a dose of 25 mg/kg for 5 weeks. Neurobehavioral performance was observed, and serum concentrations of insulin and Nesfatin-1 were measured. Moreover, the protein expression of amyloid beta 1-42 (Aß1-42), Tau, phosphorylated Tau (p-Tau) (Ser396), synaptic ras GTPase activation protein (SynGAP), postsynaptic density protein 95 (PSD95), synapsin-1, synaptogomin-1, and key molecules of the Wnt/ß-catenin signaling pathway in the hippocampus and prefrontal cortex (PFC) were assessed. Finally, pathological damage to hippocampal tissue was examined by Nissl and immunofluorescence staining. The results showed that compared with the controls, bilateral hippocampal microinjections of STZ induced task-specific learning and memory impairments, as indicated by the disadvantaged performances in the novel object recognition test (NOR) and Morris water maze (MWM), but not the contextual fear conditioning test (CFC). Treatment with RES could improve these behavioral disadvantages. The serum concentrations of insulin and Nesfatin-1 in the model group were remarkably higher than those of the control group. In addition, protein expression of Aß1-42, Tau, and p-Tau (Ser396) was increased but expression of SynGAP, PSD95, brain-derived neurotrophic factor (BDNF), and p-GSK-3ß/GSK-3ß were decreased in the hippocampus. Although the protein expression of BDNF and SynGAP was also markedly decreased in the PFC of the model mice, there was no significant difference among groups in the protein expression of PSD95, BDNF, synapsin-1, synaptogomin-1, and p-GSK-3ß/GSK-3ß. RES (25 mg/kg) reversed the enhanced insulin level, the abnormal protein expression of Aß1-42, Tau, and p-Tau (Ser396) in the hippocampus and PFC, and the hippocampal protein expression of SynGAP, PSD95 and BDNF. In addition, RES reversed the STZ-induced decrease in the number of Nissl bodies and the increase in fluorescence intensity of IBA1 in the hippocampal CA1 region. These findings indicate that RES could ameliorate STZ-induced AD-like neuropathological injuries, the mechanism of which could be partly related to its regulation of BDNF expression and synaptic plasticity-associated proteins in the hippocampus.

Bilateral intracerebroventricular injection of streptozotocin induces AD-like behavioral impairments and neuropathological features in mice: Involved with the fundamental role of neuroinflammation.

OBJECTIVE: To establish an Alzheimer's disease (AD) mouse model, investigate the behavioral performance changes and intracerebral molecular changes induced by bilateral intracerebroventricular injection of streptozotocin (STZ/I.C.V), and explore the potential pathogenesis of AD. METHODS: An AD mouse model was established by STZ/I.C.V. The behavioral performance was observed via the open field test (OFT), novel object recognition test (NOR), and tail suspension test (TST). The mRNA and protein expressions of interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α) in the hippocampus were measured via qPCR and Western blot. The expression of ß-amyloid 1-42 (Aß1-42), phosphorylated Tau protein (p-Tau (Ser396)), Tau5, ß-site amyloid precursor protein (APP) cleaving enzyme (BACE), insulin receptor substrate 1 (IRS1), brain-derived neurotrophic factor (BDNF), Copine6, synaptotagmin-1 (Syt-1), synapsin-1, phosphoinositol 3 kinase (PI3K), serine/threonine kinase (Akt), phosphorylated serine/threonine kinase (p-Akt (Ser473)), triggering receptor expressed on myeloid cells-1/2 (TREM1/2) were detected using Western blot, and the expression of glial fibrillary acidic protein (GFAP), ionized calcium binding adapter molecule 1 (IBA1), Aß1-42, p-Tau(Ser396), Syt-1, BDNF were measured via immunofluorescence staining. RESULTS: STZ/I.C.V induced AD-like neuropsychiatric behaviors in mice, as indicated by the impairment of learning and memory, together with the reduced spontaneous movement and exploratory behavior. The expression of BACE, Aß1-42, p-Tau(Ser396), and TREM2 were significantly increased in the hippocampus of model mice, while the expression of IRS1, BDNF, Copine6, Syt-1, synapsin-1, PI3K, p-Akt(Ser473), and TREM1 were decreased as compared with that of the controls. Furthermore, the model mice presented a hyperactivation of astrocytes and microglia in the hippocampus, accompanied by the increased mRNA and protein expressions of IL-1ß, IL-6 and TNF-α. CONCLUSION: STZ/I.C.V is an effective way to induce AD mice model, with not only AD-like neuropsychiatric behaviors, but also typic AD-like neuropathological features including neurofibrillary tangles, deposit of ß-amyloid (Aß), neuroinflammation, and imbalanced synaptic plasticity.

MicroRNAs in Alzheimer's disease: Potential diagnostic markers and therapeutic targets.

Alzheimer's disease (AD) is the most common neurodegenerative disease, with cognitive decline as the primary clinical feature. According to epidemiological statistics, 50 million people worldwide are currently affected by Alzheimer's disease. Although new drugs such as aducanumab have been approved for use in the treatment of AD, none of them have reversed the progression of AD. MicroRNAs (miRNAs) are small molecule RNAs that exert their biological functions by regulating the expression of intracellular proteins, and differential abundance and varieties are found between the central and peripheral tissues of AD patients and healthy controls. This article will summarise the changes of miRNAs in the AD process, and the potential role of diagnostic markers and therapeutic targets in AD will be explored.

Exosomes derived from bone-marrow mesenchymal stem cells alleviate cognitive decline in AD-like mice by improving BDNF-related neuropathology.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive decline in cognitive ability. Exosomes derived from bone-marrow mesenchymal stem cells (BMSC-exos) are extracellular vesicles that can execute the function of bone-marrow mesenchymal stem cells (BMSCs). Given the versatile therapeutic potential of BMSC and BMSC-exos, especially their neuroprotective effect, the aim of this study was to investigate the potential effect of BMSC-exos on AD-like behavioral dysfunction in mice and explore the possible molecular mechanism. METHODS: BMSC-exos were extracted from the supernatant of cultured mouse BMSCs, which were isolated from the femur and tibia of adult C57BL/6 mice, purified and sorted via flow cytometry, and cultured in vitro. BMSC-exos were identified via transmission electron microscopy, and typical marker proteins of exosomes were also detected via Western blot. A sporadic AD mouse model was established by intracerebroventricular injection of streptozotocin (STZ). Six weeks later, BMSC-exos were administered via lateral ventricle injection or caudal vein injection lasting five consecutive days, and the control mice were intracerebroventricularly administered an equal volume of solvent. Behavioral performance was observed via the open field test (OFT), elevated plus maze test (EPM), novel object recognition test (NOR), Y maze test (Y-maze), and tail suspension test (TST). The mRNA and protein expression levels of IL-1ß, IL-6, and TNF-α in the hippocampus were measured via quantitative polymerase chain reaction (qPCR) and Western blot, respectively. Moreover, the protein expression of Aß1-42, BACE, IL-1ß, IL-6, TNF-α, GFAP, p-Tau (Ser396), Tau5, synaptotagmin-1 (Syt-1), synapsin-1, and brain-derived neurotrophic factor (BDNF) in the hippocampus was detected using Western blot, and the expression of GFAP, IBA1, Aß1-42 and DCX in the hippocampus was measured via immunofluorescence staining. RESULTS: Lateral ventricle administration, but not caudal vein injection of BMSC-exos improved AD-like behaviors in the STZ-injected mouse model, as indicated by the increased number of rearing, increased frequency to the central area, and increased duration and distance traveled in the central area in the OFT, and improved preference index of the novel object in the NOR. Moreover, the hyperactivation of microglia and astrocytes in the hippocampus of the model mice was inhibited after treatment with BMSC-exos via lateral ventricle administration, accompanied by the reduced expression of IL-1ß, IL-6, TNF-α, Aß1-42, and p-Tau and upregulated protein expression of synapse-related proteins and BDNF. Furthermore, the results of the Pearson test showed that the preference index of the novel object in the NOR was positively correlated with the hippocampal expression of BDNF, but negatively correlated with the expression of GFAP, IBA1, and IL-1ß. Apart from a positive correlation between the hippocampal expression of BDNF and Syt-1, BDNF abundance was found to be negatively correlated with markers of glial activation and the expression of the inflammatory cytokines, Aß1-42, and p-Tau, which are characteristic neuropathological features of AD. CONCLUSIONS: Lateral ventricle administration, but not caudal vein injection of BMSC-exos, can improve AD-like behavioral performance in STZ-injected mice, the mechanism of which might be involved in the regulation of glial activation and its associated neuroinflammation and BDNF-related neuropathological changes in the hippocampus.

Impaired Learning and Memory Ability Induced by a Bilaterally Hippocampal Injection of Streptozotocin in Mice: Involved With the Adaptive Changes of Synaptic Plasticity.

Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive decline, psychiatric symptoms and behavioral disorders, resulting in disability, and loss of self-sufficiency. Objective: To establish an AD-like mice model, investigate the behavioral performance, and explore the potential mechanism. Methods: Streptozotocin (STZ, 3 mg/kg) was microinjected bilaterally into the dorsal hippocampus of C57BL/6 mice, and the behavioral performance was observed. The serum concentrations of insulin and nesfatin-1 were measured by ELISA, and the activation of hippocampal microglia and astrocytes was assessed by immunohistochemistry. The protein expression of several molecular associated with the regulation of synaptic plasticity in the hippocampus and the pre-frontal cortex (PFC) was detected via western blotting. Results: The STZ-microinjected model mice showed a slower bodyweight gain and higher serum concentration of insulin and nesfatin-1. Although there was no significant difference between groups with regard to the ability of balance and motor coordination, the model mice presented a decline of spontaneous movement and exploratory behavior, together with an impairment of learning and memory ability. Increased activated microglia was aggregated in the hippocampal dentate gyrus of model mice, together with an increase abundance of Aß1-42 and Tau in the hippocampus and PFC. Moreover, the protein expression of NMDAR2A, NMDAR2B, SynGAP, PSD95, BDNF, and p-ß-catenin/ß-catenin were remarkably decreased in the hippocampus and the PFC of model mice, and the expression of p-GSK-3ß (ser9)/GSK-3ß were reduced in the hippocampus. Conclusion: A bilateral hippocampal microinjection of STZ could induce not only AD-like behavioral performance in mice, but also adaptive changes of synaptic plasticity against neuroinflammatory and endocrinal injuries. The underlying mechanisms might be associated with the imbalanced expression of the key proteins of Wnt signaling pathway in the hippocampus and the PFC.

Mediator Med23 Regulates Adult Hippocampal Neurogenesis.

Mammalian Mediator (Med) is a key regulator of gene expression by linking transcription factors to RNA polymerase II (Pol II) transcription machineries. The Mediator subunit 23 (Med23) is a member of the conserved Med protein complex and plays essential roles in diverse biological processes including adipogenesis, carcinogenesis, osteoblast differentiation, and T-cell activation. However, its potential functions in the nervous system remain unknown. We report here that Med23 is required for adult hippocampal neurogenesis in mouse. Deletion of Med23 in adult hippocampal neural stem cells (NSCs) was achieved in Nestin-CreER:Med23flox/flox mice by oral administration of tamoxifen. We found an increased number of proliferating NSCs shown by pulse BrdU-labeling and immunostaining of MCM2 and Ki67, which is possibly due to a reduction in cell cycle length, with unchanged GFAP+/Sox2+ NSCs and Tbr2+ progenitors. On the other hand, neuroblasts and immature neurons indicated by NeuroD and DCX were decreased in number in the dentate gyrus (DG) of Med23-deficient mice. In addition, these mice also displayed defective dendritic morphogenesis, as well as a deficiency in spatial and contextual fear memory. Gene ontology (GO) analysis of hippocampal NSCs revealed an enrichment in genes involved in cell proliferation, Pol II-associated transcription, Notch signaling pathway and apoptosis. These results demonstrate that Med23 plays roles in regulating adult brain neurogenesis and functions.

All-trans Retinoic Acid-induced Abnormal Hippocampal Expression of Synaptic Genes SynDIG1 and DLG2 is Correlated with Anxiety or Depression-Like Behavior in Mice.

Clinical reports suggest a potential link between excess retinoids and development of depression. Although it has been shown that all-trans retinoic acid (ATRA) administration induces behavioral changes, further insight into how ATRA is involved is lacking. The hippocampus seems to be a major target of retinoids, and abnormal synaptic plasticity of the hippocampus is involved in depression. We examined two genes associated with synaptic function, discs large homolog 2 (DLG2), and synapse differentiation-inducing gene protein 1 (SynDIG1) in terms of hippocampal expression and correlation with behavior. Three different doses of ATRA were injected into young mice and 10 mg/kg ATRA was found to induce depression-like behavior. In the hippocampus, DLG2 mRNA was significantly decreased by ATRA. mRNA levels were positively correlated with central area duration and distance in the open-field test. Increased SynDIG1 mRNA levels were observed. There was a negative correlation between SynDIG1 mRNA levels and mobility time in the forced swimming test. Retinoic acid receptor γ mRNA was significantly positively correlated with DLG2 and negatively correlated with SynDIG1. To summarize, ATRA administration induced anxiety- and depression-like behavior accompanied by a decreased expression of DLG2 and an increased expression of SynDIG1. Moreover, DLG2 was correlated with anxiety-like behavior and SynDIG1 was correlated with depression-like behavior. These results might constitute a novel target underlying ATRA-induced anxiety- and depression-like behavior.

Life cycle assessment of rare earths recovery from waste fluorescent powders - A case study in China.

Life cycle assessment of recycling rare earths from waste fluorescent powders was conducted, including the uncertainty and sensitivity analyses. Three scenarios were set in this study, namely, recycling with/without final disposal and waste fluorescent powders landfill. Recycling with final disposal presented lower environmental burden than that without final disposal due to the significant reduction of direct emissions. The evident impacts from chemicals and energy production stages were considered the main contributors to the overall environmental burden of recycling with final disposal due to their relatively high emissions of particulates matter, sulfur dioxide, heavy metals, and carbon dioxide as well as the use of fossil fuel. Compared with landfills, rare-earth recycling shows the highest environmental benefits because of the substitution of primary rare earths. To relieve the high demand of rare earths and reduce the overall environmental burden, governments are highly recommended to increase recycle rate, create a complete management system, improve energy consumption and wastewater treatment efficiency, and build an adequate recycle standard.

Loss of transforming growth factor-ß1 in epithelium cells affects enamel formation in mice.

OBJECTIVES: In order to understand the specific in vivo function of transforming growth factor-beta1 (TGF-ß1), we successfully established aTGF-ß1 deficient mouse model using a conditional knockout method. In the present study, we aimed to further understand the potential role of TGF-ß1 in enamel formation. DESIGN: Transgenic mice withoutTGF-ß1 in epithelial cells were generated. Scanning electron microscopy and micro-computed tomography analysis were used to detect the dental appearance, enamel microstructure and tooth density. Histological analysis was used to examine the residual organic matrix of enamel. Quantitative real-time polymerase chain reaction was used to analyze the expressions of enamel matrix proteins at the mRNA level. RESULTS: The enamel of mandibular molars and incisors inTGF-ß1 conditional knockout mice displayed severe attrition and lower density compared with the wild-type littermates. A slender microstructure of enamel rod was observed, and enamel matrix proteins were retained in the enamel space at the maturation stage in conditional knockout mice. Moreover, the expressions of enamel matrix protein-encoding genes, such as amelogenin (Amelx), ameloblastin (Ambn), Enamelin (Enam) and matrix metalloproteinase-20 (Mmp-20), were increased in enamel organs of conditional knockout mice. On the other hand, the expressions of Amelotin (Amtn), kallikrein-related peptidase-4 (Klk4), C4orf26 and WD repeat-containing protein 72 (Wdr72) were dramatically decreased at the transition and maturation stages. CONCLUSIONS: TGF-ß1 played an important role in enamel mineralization through decreasing synthesis ofAmelx, Ambn and Enam and increasing synthesis of Klk4, Amtn, Corf26 and Wdr72.

Life cycle assessment and water footprint evaluation of crude steel production: A case study in China.

China, as the world's largest crude steel producer, is suffering from water scarcity and pollution. However, only a few systematic analyses on the environmental burdens and improvements of China's crude steel production have been conducted. Therefore, it is important for research to be done how China's steel industry can be improved in environment management. To help decision-makers understand this, a life cycle water footprint analysis including gray and blue water was performed based on the methodology prescribed in the ISO 14046 standard. A life cycle assessment was also conducted to improve the environmental performance of the steel industry. Results of these assessments revealed that gray water footprint, which is mainly derived from aquatic eutrophication, carcinogens, and non-carcinogens, is higher than blue water footprint. Optimizing indirect processes, including iron ore mining, magnesium oxide production, transportation, and electricity generation, played dominant roles in the reduction of gray water footprint. Furthermore, COD, Cr (VI), phosphate, BOD5, Hg, As, nitrogen oxides, particulates, and sulfur dioxide were the key substances for environmental improvements. The underestimation of direct water footprint showed the importance and urgency of implementing scientific and adequate monitoring indicators. Meanwhile, the environmental burden can be reduced by adopting a reasonable location of the steel industry on the basis of regional water resources and actual transportation status, improving the efficiency of raw material consumption, and optimizing the power structure.

Overexpression of EMMPRIN is associated with lymph node metastasis and advanced stage of non-small cell lung cancer: a retrospective study.

BACKGROUND: Previous studies show that overexpression of EMMPRIN involved in the malignant biological behavior of tumors. This investigation was to disclose the expression status of EMMPRIN in non-small cell lung cancer (NSCLC) and its clinical value for the diagnosis of NSCLC. METHODS: The expression of EMMPRIN was examined using immunohistochemistry and enzyme-linked immunosorbent assay. The clinical value of EMMPRIN was evaluated by drawing a receiver operating characteristic (ROC) curve. RESULTS: NSCLC tissues and serum exhibited higher expression levels of EMMPRIN than the normal control (p < 0.05), and the expression of the EMMPRIN was significantly associated with lymphatic invasion and advanced stage of NSCLC (p < 0.05). ROC curve suggested that the threshold level of serum EMMPRIN for distinguishing NSCLC from control group was 80.3 pg/mL, and displayed a sensitivity of 97.22% and a specificity of 95%. And higher EMMPRIN expression in serum and tissues appeared to be risk factors for NSCLC development (risk ratio =1.56 and 1.1). CONCLUSION: Overexpression of EMMPRIN was associated with lymphatic metastasis and advanced stage of NSCLC and test of serum EMMPRIN contributes to the NSCLC diagnosis.

Increased HSP27 correlates with malignant biological behavior of non-small cell lung cancer and predicts patient's survival.

Heat shock protein 27 (HSP27) has been found to be related to tumorigenesis. The aim of this study was to investigate the expression pattern and clinical significance of HSP27 in non-small-cell lung cancer (NSCLC). The expression of HSP27 in tissues was examined by immunohistochemistry and serum level of HSP27 mRNA was detected by real-time PCR. The survival analysis was performed by a Kaplan Meier method and the estimation of risk factors was determined by the multiple regression analysis. The expression of HSP27 was increased in lung cancer tissues (p < 0.001) and serum (p < 0.001) of NSCLC patients and higher HSP27 in lung cancer tissues and serum of NSCLC patients was associated with poorly differentiated cancer (p < 0.001; p = 0.035), lymphatic metastasis (p < 0.001; p < 0.001), advanced TNM stage (p < 0.001; p < 0.001). And the levels of HSP27 in tissues and serum of lung cancer patients had a certain positive correlation (p = 0.046). Moreover, increased HSP27 expression correlated with shorter survival of NSCLC patients (p < 0.001). The results suggest that HSP27 may serve as a potential biomarker for diagnosis and prognosis of NSCLC.

Upregulation of miR-3607 promotes lung adenocarcinoma proliferation by suppressing APC expression.

Lung cancer is the leading cause of worldwide cancer-related deaths, although many drugs and new therapeutic approaches have been used, the 5-years survival rate is still low for lung cancer patients. microRNAs have been shown to regulate lung cancer initiation and development, here we studied the role of miR-3607 in lung cancer cell proliferation. We found miR-3607 was upregulated in lung cancer tissues and cells, miR-3607 overexpression promoted lung cancer cell A549 proliferation determined by MTT assay, colony formation assay, anchorage-independent growth ability assay and bromodeoxyuridine incorporation assay, while the opposite phenotypes were shown when miR-3607 was knocked down. Predicted analysis suggested a Wnt signaling pathway regulator adenomatous polyposis coli (APC) was the target of miR-3607, miR-3607 could directly bind to the 3'UTR of APC, and promoted Cyclin D1 and c-Myc expression which can be suppressed by APC. Double knockdown of miR-3607 and APC copied the phenotypes of miR-3607 overexpression, suggesting miR-3607 promoted lung cancer cell A549 proliferation by targeting APC. In conclusion, our study suggested miR-3607 contributes to lung cancer cell proliferation by inhibiting APC.

Oxytocin is implicated in social memory deficits induced by early sensory deprivation in mice.

Early-life sensory input plays a crucial role in brain development. Although deprivation of orofacial sensory input at perinatal stages disrupts the establishment of the barrel cortex and relevant callosal connections, its long-term effect on adult behavior remains elusive. In this study, we investigated the behavioral phenotypes in adult mice with unilateral transection of the infraorbital nerve (ION) at postnatal day 3 (P3). Although ION-transected mice had normal locomotor activity, motor coordination, olfaction, anxiety-like behaviors, novel object memory, preference for social novelty and sociability, they presented deficits in social memory and spatial memory compared with control mice. In addition, the social memory deficit was associated with reduced oxytocin (OXT) levels in the hypothalamus and could be partially restored by intranasal administration of OXT. Thus, early sensory deprivation does result in behavioral alterations in mice, some of which may be associated with the disruption of oxytocin signaling.