Abstract:Methamphetamine is the most widely abused drug in China recent years with more registered people in methamphetamine than that in heroin, and the situation is getting more and more worse. The emotional dysfunction is one of the most important factors to induce relapse in methamphetamine addiction, which caused by the deficit on the structure and function of prefrontal-mesolimbic circuits innervated by monoamine and amino acid neurotransmitters. The present review summarizes the advances in identifying the characteristics of emotional dysfunction manifested in three dimensions: decreased emotional awareness and positive emotion experience, increased negative emotional experience and impaired emotion regulation, and the neural mechanism focused on the prefrontal-limbic circuits underlying the emotional dysfunction. It is found that the irritability and intense anger are the most prominent features of abnormal emotion in methamphetamine addicts even in protracted abstinence periods, which will cause aggressive behaviors and induce relapse. The future studies should pay more attention to identifying the unique features of emotional dysfunction in methamphetamine addiction. Intervention and treatment targeted to emotional dysfunction are also summarized in the present review, which includes pharmaceutical drugs, neuromodulation technology and cognitive and behavioral therapy, etc. With the advances in brain science and computer sciences, future clinical researches will employ neuromodulation methods interfaced on the virtual reality technology integrated multiple sensory emotional information to treat the emotional dysfunction in methamphetamine addiction.

Abstract:Non-obstructive azoospermia (NOA) with meiotic arrest is largely unknown in the majority of male infertility, which affecting about 0.6% of men from the general population and 10% of infertile men. NOA is a complicated disease caused by multiple factors which featured high genetic and phenotype heterogeneity. This condition is related to known genetic disorders, including chromosomal abnormality, Y-chromosome microdeletions, single-gene mutation and epigenetic modification. Currently, the diagnosis and treatment of patients with NOA was limited to routine epididymal puncture biopsy, karyotype analysis and Y-chromosome microdeletion detection in the clinical. Effective diagnosis and treatment strategies were deficiency for NOA with complicated etiology. Therefore, a more comprehensive exploration of the molecular mechanism of NOA will be helpful to clarify the genetic causes of non-obstructive azoospermia, the clinical diagnosis and treatment of male infertility. In this paper, we comprehensively reviewed the several aspect of NOA, including the genetic basis of NOA, the pathological features of NOA, the clinical diagnosis and treatment of NOA.

Abstract:As newly found cellular stress response, the mitochondrial unfolded protein response (UPR^mt) is associated with the pathological process of aging, cancer and neurodegenerative diseases. To maintain mitochondrial protein homeostasis, cell will inspire UPR^mt program by activating the transcription of mitochondrial chaperones and proteases encoded by nuclear DNA. Exploring the mechanisms of UPRmt is essential for understanding the pathological process of aging and mitochondria-related diseases. In this review, we focus on various inducers of UPR^mt, the different mechanisms of UPR^mt, the regulatory factors, and relationship with aging, immunity and other diseases in C. elegans and mammalian cells to provide new theoretical basis and therapeutic target for these diseases.

Abstract:Dysmetabolism of endogenous formaldehyde is regarded as one of the risk factors for the onset and progression of Alzheimer’s disease. Excess extracellular and intracellular formaldehyde induce neuron death, involving the impairment of cognitive ability. As previously reported, lysosome dysfunction plays an important role in neurodegenerative diseases and intracellular formaldehyde locates in the lysosome. Utilizing formaldehyde fluorescent probe, abnormally increase of the lysosomal formaldehyde was detected in the blood endothelial cell line (bEnd.3) and neuroblastoma N2a cells (N2a) from mouse brain under oxidative stress. Brain formaldehyde was significantly (P < 0.01) elevated in the chronic cerebral hypoperfusion rats compared with those with SHAM. LeuLeuOMe was used to induce the permeabilization of lysosome membrane in bEnd.3. After LeuLeuOMe tretment, higher intracellular and lower extracellular formaldehyde were measured by microplate reader and high performance liquid chromatography (HPLC) respectively. In other words, lysosome not only accommodates endogenous formaldehyde, but also transports the compound out of cells. Abnormal lysosome function causes dysmetabolism of formaldehyde, which is correlated with age-related cognitive impairment.

Abstract:Heat shock is a common stress for life, while algae develops high efficient adaptation ability to heat shock during longtime evolution. Up to date, the researches about the mechanism of heat shock adaptation in algae focus just on physiological regulation and related coding genes, while there are few reports about non-coding genes on it. In the previous study, we found that Cre-miR914 were down-regulated significantly under multiple stresses (heat shock, UV-B and salinity) in Chlamydomonas reinhardtii through Q-PCR screening experiments, and bioinformatics analysis showed that the target gene of Cre-miR914 may be RPL18. But the functions of Cre-miR914 and its target gene in heat shock adaptation are unclear, this study addressed these issues through multiple experiments. In this study, we identified the target of Cre-miR914 through bioinformatics and degradome sequencing, and validated expression of Cre-miR914 and RPL18 under heat shock through Q-PCR. Then we constructed cell lines of Cre-miR914 overexpression and RPL18 overexpression for further study. And finally we performed stress adaptation experiments under heat shock stress to check the function of microRNA and its target in stress adaptation, which includes cell growth assay, cell vitality counting, reactive oxygen species (ROS) production and lipid peroxidation (MDA) measurements. Bioinformatics and degradome sequencing indicated the target of Cre-miR914 is RPL18/i>; Q-PCR results showed that Cre-miR914 expression reduced under heat shock, but RPL18 expression increased, which confirmed our previous results of screening experiment. Then we got more than 3 cell lines with overexpressing of Cre-miR914 and RPL18. Further growth experiment under heat shock indicated that Cre-miR914 overexpression lines had a lower growth than the wild-type line (cw15), while RPL18 overexpression lines had a higher growth than the wild-type line (cw15). Cells vitality (photosynthesis activity) experiment under stress also demonstrated that Cre-miR914 overexpression lines had a lower vitality than the wild-type line (cw15), while RPL18 overexpression lines had a higher vitality. The cell damage (ROS production and MDA content) experiments showed that there were more cell damages (ROS production and MDA content) in Cre-miR914 overexpression lines than the wild-type line (cw15), while that of RPL18 overexpression lines were lower than the wild-type line (cw15). These results illustrated that overexpression of Cre-miR914 reduced heat shock resistance ability in algae, while overexpression of RPL18 increased heat shock resistance ability. We maybe discovered a new regulation mechanism of heat shock adaptation in algae, in which Cre-miR914 and its target gene RPL18 are engaged in adaptation regulation to heat shock in Chlamydomonas reinhardtii.