Up-regulating GABA transporter-3 in the zona incerta prevents surgery-induced memory impairment in mice.

Clinical surgery can lead to severe neuroinflammation and cognitive dysfunctions. It has been reported that astrocytes mediate memory formation and postoperative cognitive dysfunction (POCD), however, the thalamic mechanism of astrocytes in mediating POCD remains unknown. Here, we report that reactive astrocytes in zona incerta (ZI) mediate surgery-induced recognition memory impairment in male mice. Immunostaining results showed that astrocytes are activated with GABA transporter-3 (GAT-3) being down-expressed, and neurons were suppressed in the ZI. Besides, our work revealed that reactive astrocytes caused increased tonic current in ZI neurons. Up-regulating the expression of GAT-3 in astrocytes ameliorates surgery-induced recognition memory impairment. Together, our work demonstrates that the reactive astrocytes in the ZI play a crucial role in surgery-induced memory impairment, which provides a new target for the treatment of surgery-induced neural dysfunctions.

Glutamatergic Projection from the Ventral Tegmental Area to the Zona Incerta Regulates Fear Response.

Innate defensive behavior is important for animal survival. The Vglut2+ neurons in the ventral tegmental area (VTA) have been demonstrated to play important roles in innate defensive behaviors, but the neural circuit mechanism is still unclear. Here, we find that VTA - zona incerta (ZI) glutamatergic projection is involved in regulating innate fear responses. Combining calcium signal recording and chemogentics, we find that VTA-Vglut2+ neurons respond to foot shock stimulus. Inhibition of VTA-Vglut2+ neurons reduces foot shock-evoked freezing, while chemogentic activation of these neurons results in an enhanced fear response. Using viral tracing and immunofluorescence, we show that VTA - Vglut2+ neurons send direct excitatory outputs to the ZI. Moreover, we find that the activity of VTAVglut2 - ZI projection is pivotal in modulating fear response. Together, our study reveals a new VTA - ZI glutamatergic circuit in mediating innate fear response and provides a potential target for treating post-traumatic stress disorder.

The purified extract of steamed Panax ginseng protects cardiomyocyte from ischemic injury via caveolin-1 phosphorylation-mediating calcium influx.

Background: Caveolin-1, the scaffolding protein of cholesterol-rich invaginations, plays an important role in store-operated Ca2+ influx and its phosphorylation at Tyr14 (p-caveolin-1) is vital to mobilize protection against myocardial ischemia (MI) injury. SOCE, comprising STIM1, ORAI1 and TRPC1, contributes to intracellular Ca2+ ([Ca2+]i) accumulation in cardiomyocytes. The purified extract of steamed Panax ginseng (EPG) attenuated [Ca2+]i overload against MI injury. Thus, the aim of this study was to investigate the possibility of EPG affecting p-caveolin-1 to further mediate SOCE/[Ca2+]i against MI injury in neonatal rat cardiomyocytes and a rat model. Methods: PP2, an inhibitor of p-caveolin-1, was used. Cell viability, [Ca2+]i concentration were analyzed in cardiomyocytes. In rats, myocardial infarct size, pathological damages, apoptosis and cardiac fibrosis were evaluated, p-caveolin-1 and STIM1 were detected by immunofluorescence, and the levels of caveolin-1, STIM1, ORAI1 and TRPC1 were determined by RT-PCR and Western blot. And, release of LDH, cTnI and BNP was measured. Results: EPG, ginsenosides accounting for 57.96%, suppressed release of LDH, cTnI and BNP, and protected cardiomyocytes by inhibiting Ca2+ influx. And, EPG significantly relieved myocardial infarct size, cardiac apoptosis, fibrosis, and ultrastructure abnormality. Moreover, EPG negatively regulated SOCE via increasing p-caveolin-1 protein, decreasing ORAI1 mRNA and protein levels of ORAI1, TRPC1 and STIM1. More importantly, inhibition of the p-caveolin-1 significantly suppressed all of the above cardioprotection of EPG. Conclusions: Caveolin-1 phosphorylation is involved in the protective effects of EPG against MI injury via increasing p-caveolin-1 to negatively regulate SOCE/[Ca2+]i.

Two parallel medial prefrontal cortex-amygdala pathways mediate memory deficits via glutamatergic projection in surgery mice.

The neural circuit mechanisms underlying postoperative cognitive dysfunction (POCD) remain elusive. We hypothesized that projections from the medial prefrontal cortex (mPFC) to the amygdala are involved in POCD. A mouse model of POCD in which isoflurane (1.5%) combined with laparotomy was used. Virally assisted tracing techniques were used to label the relevant pathways. Fear conditioning, immunofluorescence, whole-cell patch-clamp recordings, and chemogenetic and optogenetic techniques were applied to investigate the role of mPFC-amygdala projections in POCD. We find that surgery impairs memory consolidation but not retrieval of consolidated memories. In POCD mice, the glutamatergic pathway from the prelimbic cortex to the basolateral amygdala (PL-BLA) shows reduced activity, whereas the glutamatergic pathway from the infralimbic cortex to the basomedial amygdala (IL-BMA) shows enhanced activity. Our study indicates that the hypoactivity in the PL-BLA pathway interrupts memory consolidation, whereas the hyperactivity in the IL-BMA promotes memory extinction, in POCD mice.

[Spatiotemporal dynamics of soil salinity in the Yellow River Delta under the impacts of hydrology and climate.] / 水文气候影响下黄河三角洲土壤盐分时空动态.

In recent years, soil salinization in the Yellow River Delta under the effects of hydrology, climate and human activities have become increasingly prominent. Based on the 20 Landsat series images of Hekou, Kenli, Dongying districts and Lijin County of Dongying City selected from 1985 to 2018, numerical regression correction method was used to perform image spectral consistency conversion. The partial least squares regression method was used to construct quantitative inversion models of soil salt content. The soil salt content of the study area were retrieved by the best salt prediction model. The temporal and spatial characteristics of soil salt changes in the Yellow River Delta were analyzed. The results showed that the soil salt inversion model constructed with 10 sensitive spectral indices performed higher prediction accuracy, with coefficient of determination R2=0.769 and RMSE=1.125 for calibration, R2=0.752 and RMSE=1.203 for validation, and relative prediction deviation (RPD)=2.08. Using the measured soil salt data in 2016 to verify the inversion accuracy of the model, the correlation between the measured value and the inverted value was 0.7279. The model was used to map the soil salinity of the Yellow River Delta based on 20 images from 1985 to 2018. The abnormal soil salinity retrieval values was all less than 10%. During the study period, the soil salinity showed an overall trend of rising first and then falling which was lowest in 1985 (3.14 g·kg-1) and highest in 1995 (5.86 g·kg-1). Spatially, the area of heavily saline soil and saline soil in the study area decreased, and that of mildly and moderately saline soil significantly increased (66.6%). The total area of saline soil showed an increasing trend. The effects of hydrological and climatic conditions on soil salinity exhibited hysteresis. The increases of temperature promoted soil salinity, with the relationship between the soil salinity and the average temperatures in the past six months and one year being significantly correlated (R=0.507 and 0.538). Soil salinity did not correlate with regional precipitation, and was most affected by the Yellow River streamflow in the previous season (R=-0.543).

Effects of Hyaluronic Acid on Stability of Bleomycin Foam.

BACKGROUND: Bleomycin (BLM) foam sclerotherapy is effective in the treatment of venous malformations (VMs). Foam stability is influenced by factors such as sclerosant concentration, viscosity, and liquid-gas ratio. OBJECTIVE: To investigate whether hyaluronic acid (HA) could increase the stability of BLM foam and to evaluate the safety and efficacy of HA-BLM foam. MATERIALS AND METHODS: Experiment: BLM 6.0 IU + human serum albumin (HSA, 2, 1.95, 1.90, and 1.85 mL, respectively) + 1% HA (0, 0.05, 0.10, and 0.15 mL, respectively) + air 6 mL to create foam using the Tessari method. The foam half-life (FHL) was used to evaluate foam stability. Clinical study: Twenty-eight patients with head and neck VMs were enrolled between June 2018 and August 2019 treated by HA-BLM foam to evaluate the safety and efficacy. RESULTS: The FHL of the BLM foam was 8.46, 8.95, 10.45, and 14.51 minutes, respectively. All patients achieved significant efficacy, and no obvious side effects were observed. CONCLUSION: Addition of HA could improve the stability of BLM foam.

HDAC2 hyperexpression alters hippocampal neuronal transcription and microglial activity in neuroinflammation-induced cognitive dysfunction.

BACKGROUND: Inflammation can induce cognitive dysfunction in patients who undergo surgery. Previous studies have demonstrated that both acute peripheral inflammation and anaesthetic insults, especially isoflurane (ISO), are risk factors for memory impairment. Few studies are currently investigating the role of ISO under acute peri-inflammatory conditions, and it is difficult to predict whether ISO can aggravate inflammation-induced cognitive deficits. HDACs, which are essential for learning, participate in the deacetylation of lysine residues and the regulation of gene transcription. However, the cell-specific mechanism of HDACs in inflammation-induced cognitive impairment remains unknown. METHODS: Three-month-old C57BL/6 mice were treated with single versus combined exposure to LPS injected intraperitoneally (i.p.) to simulate acute abdominal inflammation and isoflurane to investigate the role of anaesthesia and acute peripheral inflammation in cognitive impairment. Behavioural tests, Western blotting, ELISA, immunofluorescence, qRT-PCR, and ChIP assays were performed to detect memory, the expressions of inflammatory cytokines, HDAC2, BDNF, c-Fos, acetyl-H3, microglial activity, Bdnf mRNA, c-fos mRNA, and Bdnf and c-fos transcription in the hippocampus. RESULTS: LPS, but not isoflurane, induced neuroinflammation-induced memory impairment and reduced histone acetylation by upregulating histone deacetylase 2 (HDAC2) in dorsal hippocampal CaMKII+ neurons. The hyperexpression of HDAC2 in neurons was mediated by the activation of microglia. The decreased level of histone acetylation suppressed the transcription of Bdnf and c-fos and the expressions of BDNF and c-Fos, which subsequently impaired memory. The adeno-associated virus ShHdac2, which suppresses Hdac2 after injection into the dorsal hippocampus, reversed microglial activation, hippocampal glutamatergic BDNF and c-Fos expressions, and memory deficits. CONCLUSIONS: Reversing HDAC2 in hippocampal CaMKII+ neurons exert a neuroprotective effect against neuroinflammation-induced memory deficits.

De Novo Assembled Transcriptome Analysis and Identification of Genic SSR Markers in Red-Flowered Strawberry.

Red-flowered strawberry is a new ornamental flower derived from intergeneric hybridization (Fragaria × Potentilla). To date, few molecular markers have been reported for this plant. RNA sequencing provides a relatively fast and low-cost approach for large-scale detection of simple sequence repeats (SSRs). In the present study, we profiled the transcriptome of red-flowered strawberry by Illumina HiSeq 2500 to identify SSRs related to petal color. Based on 2 million clean reads of red and white flowers from red-flowered strawberry hybrids, we assembled 91,835 unigenes with an average length of 717 bp. After functional annotation and prediction, there were 47,058 unigenes; of these, 26,861 had a gene ontology annotation, with 14,264 SSR loci. Mononucleotide SSRs were the predominant repeat type (47.20%, n = 6724), followed by di- (32.50%, n = 4641), tri- (19.10%, n = 2729), tetra- (0.90%, n = 132), hexa- (0.2%, n = 21), and penta- (0.10%, n = 16) nucleotide repeats. The most frequent di-, tri-, and tetra-nucleotide repeats were AG/CT, AAG/CTT, and AAAG/CTTT, respectively. PCR amplification with 105 SSR primer pairs yielded four bands specific to red flowers, namely UgRFsr57622, UgRFsr94149, UgRFsr40142, and UgRFsr54608; corresponding 4 trait-specific markers were found to co-segregate with white and red flower color in hybrid population, demonstrating that the genic SSR marker is useful to discriminate between white and red flowers in strawberry. Markers to discriminate flower color in red-flowered strawberry will be useful for early selection of progeny and for breeding management.

Expression and immunohistochemical localization of Cdc2 and P70S6K in different stages of mouse germ cells.

In order to determine the function and possible relationship between Cdc2 and P(70)S6K, Western blot analysis and immunohistochemistry analysis were used to study the expression and kinase activity of Cdc2 and P(70)S6K in male mouse germ cells. With the maturation of germ cells in the testis, the expression of Cdc2 and P(70)S6K was relatively constant. However, the kinase activity of P(70)S6K was increased and the phosphorylation of Tyr15 residue of Cdc2 was enhanced, which suggests that the kinase activity of Cdc2 is decreasing. Immunohistochemistry analysis also showed that there was a P(70)S6K transfer from nucleus to cytoplasm during spermatogenesis. During spermatogenesis, cell division of the germ cell in male mouse is decelerated; nevertheless, cell growth is enhanced. Cdc2 and P(70)S6K are involved in these two processes. It could be an alternative mechanism to prepare for future fertilization that Cdc2 is able to maintain a subtle balance between the production and growth of male germ cells by regulating P(70)S6K.

[Chromosomal localization and inhibitory effect on TPK activition of a human novel gene hbrp].

The purpose of present study is to determine the location of the novel gene hbrp which is related to bovine seminal plasma (BSP) proteins in the human chromosome by the FISH (fluorescent in situ hybridization) technique, and to investigate the relation of HBRP to TPK( tyrosine protein kinase)by genetic engineering. The result is that the novel gene hbrp was successfully localized on human chromosome 19q1.3; HBRP protein obviously inhibited the activity of PKC. It is concluded that the structure of BSP contained two tandemly arranged fibronectin type II(Fn2)--domains which were related to the function of binding protein BSP. Amino acid sequence of HBRP protein with four tandemly arranged Fn2-domains showed that the protein might be binding protein functionly relating to BSP protein. We have concluded that HBRP protein obviously inhibited the activity of TPK. The location of the novel gene on human chromosome 19q1.3 is very important to study the other biological functions of the protein encoded by gene hbrp.

Effect of aging on expression of nitric oxide synthase I and activity of nitric oxide synthase in rat penis.

AIM: To investigate the effect of aging on the expression of nitric oxide synthase I (NOS I) and the activity of NOS in rat penis. METHODS: Sixty male rats from 3 age groups (adult, old and senescent) were investigated. The expression of NOS I protein and mRNA in rat penis were detected by Western blot and RT-PCR respectively and the NOS activity, with ultraviolet spectrophotometry. RESULTS: In the old and senescent group, NOS I protein expression was significantly decreased as compared with the adult. NOS I mRNA expression was well correlated with the protein expression. NOS activity was not statistically different between the adult and old groups, but it was significantly reduced in the senescent compared with the adult group (P<0.01). CONCLUSION: The aging-induced decreases in NOS I expression and NOS activity may be one of the main mechanisms leading to erectile dysfunction in the senescent rats.