[Behavioral treatment of functional anejaculation and factors influencing the therapeutic effect].

OBJECTIVE: To study the effect of a modified behavioral treatment (MBT) on functional anejaculation and analyze the factors influencing the therapeutic efficacy. METHODS: We enrolled in this study 59 men aged 24－45 years visiting the Andrology Clinic of Shanghai First Maternity and Infant Hospital from August 2019 to May 2021 and complaining of aejaculation in sexual intercourse but normally ejaculating during masturbation. Thirty-nine of the patients underwent conventional behavioral treatment (the CBT group) and the other 20 received MBT, namely, changing the masturbation method combined with audiovisual stimulation during sexual intercourse (the MBT group). We compared the therapeutic effects between the two groups of patients, and analyzed the correlation of the outcomes of MBT with age, abstinence duration, use of audiovisual stimulation, change of the sexual position, mean bilateral testis volume and sex hormone levels. RESULTS: After treatment, 22 (37.29%) of the patients achieved successful ejaculation at least once in sexual intercourse, 11 (55.00%) in the MBT group, and the other 11 (28.21) in the CBT group, with a significantly higher effectiveness rate in the former than in the latter (P<0.05). The effectiveness rate was significantly correlated to the method of standing-position masturbation plus sexual intercourse and reduction in the frequency of masturbation among various strategies of behavioral treatment (P<0.05). CONCLUSION: MBT has a certain effect on functional anejaculation, and targeting the previous events of the patient is the key to the therapeutic efficacy. Further exploration of more effective strategies of behavioral treatment will become the trend of development in the management of functional anejaculation.

Median Raphe Nonserotonergic Neurons Modulate Hippocampal Theta Oscillations.

Hippocampal theta oscillations (HTOs) during rapid eye movement (REM) sleep play an important role in mnemonic processes by coordinating hippocampal and cortical activities. However, it is not fully understood how HTOs are modulated by subcortical regions, including the median raphe nucleus (MnR). The MnR is thought to suppress HTO through its serotonergic outputs. Here, our study on male mice revealed a more complex framework indicating roles of nonserotonergic MnR outputs in regulating HTO. We found that nonselective optogenetic activation of MnR neurons at theta frequency increased HTO amplitude. Granger causality analysis indicated that MnR theta oscillations during REM sleep influence HTO. By using three transgenic mouse lines, we found that MnR serotonergic neurons exhibited little or no theta-correlated activity during HTO. Instead, most MnR GABAergic neurons and Vglut3 neurons respectively increased and decreased activities during HTO and exhibited hippocampal theta phase-locked activities. Although MnR GABAergic neurons do not directly project to the hippocampus, they could modulate HTO through local Vglut3 and serotonergic neurons as we found that MnR GABAergic neurons monosynaptically targeted Vglut3 and serotonergic neurons. Additionally, pontine wave recorded from the MnR during REM sleep accompanied nonserotonergic activity increase and HTO acceleration. These results suggest that MnR nonserotonergic neurons modulate hippocampal theta activity during REM sleep, which regulates memory processes.SIGNIFICANCE STATEMENT The MnR is the major source of serotonergic inputs to multiple brain regions including the hippocampus and medial septal area. It has long been thought that those serotonergic outputs suppress HTOs. However, our results revealed that MnR serotoninergic neurons displayed little firing changes during HTO. Instead, MnR Vglut3 neurons were largely silent during HTO associated with REM sleep. Additionally, many MnR GABAergic neurons fired rhythmically phase-locked to HTO. These results indicate an important role of MnR nonserotonergic neurons in modulating HTO.

Single coil endovascular embolization of very tiny (≤2 mm) intracranial aneurysms: one center's experience.

Background: To investigate the safety and efficacy of endovascular embolization of very tiny (≤2 mm) intracranial aneurysms with single coil and summarize experience. Methods: A retrospective analysis was performed for 15 consecutive patients with very tiny aneurysms treated by coil embolization alone or stent-assisted coil embolization between January 2017 and January 2020. 15 patients with six unruptured aneurysms and nine ruptured aneurysms were included in this study. There were eight males and seven females with a mean age of 50.0 ± 5.2 years (range 41 to 57 years old). Intraoperative complications, imaging outcomes, clinical outcomes and follow-up data were analyzed. Results: All aneurysms were embolized with a single coil. Lvis stents were used in all coil assisted embolizations. The embolization success rate was 100%. The average volume embolization ratio (VER) of aneurysm embolization was 53.7 ± 25.5%. An intraoperative aneurysm re-rupture complication occurred in one patient (6.7%). 11 patients (73.3%) had immediate complete occlusion after embolization. After a mean follow-up period of 6.7 ± 1.4 months, 13 patients (86.7%) had complete occlusion. No patients had aneurysm re-rupture, an ischemic event or recurrence during follow-up. All patients achieved favorable clinical outcomes with a modified rankin scale (MRS) of 0-2. Conclusions: This study demonstrates that endovascular embolization of very tiny intracranial aneurysms with a single coil is safe and effective. However, the follow-up period was not long enough and studies with larger numbers of patients are required. The summary of experience reported here is expected to provide significant patient benefits.

Neurons in rat orbitofrontal cortex and medial prefrontal cortex exhibit distinct responses in reward and strategy-update in a risk-based decision-making task.

The orbitofrontal cortex (OFC) and the medial prefrontal cortex (mPFC) are known to participate in risk-based decision-making. However, whether neuronal activities of these two brain regions play similar or differential roles during different stages of risk-based decision-making process remains unknown. Here we conducted multi-channel in vivo recordings in the OFC and mPFC simultaneously when rats were performing a gambling task. Rats were trained to update strategy as the task was shifted in two stages. Behavioral testing suggests that rats exhibited different risk preferences and response latencies to food rewards during stage-1 and stage-2. Indeed, the firing patterns and numbers of non-specific neurons and nosepoking-predicting neurons were similar in OFC and mPFC. However, there were no reward-expecting neurons and significantly more reward-excitatory neurons (fired as rats received rewards) in the mPFC. Further analyses suggested that nosepoking-predicting neurons may encode the overall value of reward and strategy, whereas reward-expecting neurons show more intensive firing to a big food reward in the OFC. Nosepoking-predicting neurons in mPFC showed no correlation with decision-making strategy updating, whereas the response of reward-excitatory neurons in mPFC, which were barely observed in OFC, were inhibited during nosepoking, but were enhanced in the post-nosepoking period. These findings indicate that neurons in the OFC and mPFC exhibit distinct responses in decision-making process during reward consumption and strategy updating. Specifically, OFC encodes the overall value of a choice and is thus important for learning and strategy updating, whereas mPFC plays a key role in monitoring and execution of a strategy.

On the Interfacial Adhesion between TiO2 Nanotube Array Layer and Ti Substrate.

Anodic titania nanotube arrays (TNTAs) with higher aspect ratio are observed to be liable to spontaneous curling or delamination from the underlying titanium (Ti) metal once dried because of the poor interfacial adhesion of the TNTA layer to the underlying Ti, especially when a thin Ti sheet is used. The interfacial adhesion strength was shown to decrease with increasing thickness of the TNTA layer. In this work, although the preparation of TNTAs in a frequently used fluoride-containing solution was completed, different anodization processes were further performed at lower current densities or at lower voltages for a short time in the same electrolyte to increase the adhesion. The mechanical test demonstrated that better adhesion properties have been achieved by applying these anodization posttreatment processes. It is believed that during the fabrication of TNTAs, a large residual stress at the interface of the nanotube layer and the underlying Ti is created. It is the residual stress that leads to the weak interfacial adhesion. The anodization posttreatment processes can reduce or eliminate the residual stress, thereby improving the interfacial adhesion. Further, these processes can also boost the performances of TNTAs for supercapacitors. When the anodization posttreatment processes are implemented at 1 mA cm-2 or at 10 V for 5 min, considerable improvements in the interfacial adhesion are observed. Particularly, both posttreatment processes are also applicable to the very thin Ti sheet (∼18 µm). The realization of robust and adherent TNTAs grown on very thin Ti sheets can not only significantly improve the volumetric capacitances of TNTAs but also make TNTAs an attractive material in flexible supercapacitor applications.

[Correlation between IVF outcomes and Ureaplasma urealyticum infection in male reproductive tract].

OBJECTIVE: To investigate the influence of Ureaplasma urealyticum (Uu) infection in the male reproductive tract on the outcomes of IVF and the clinical significance of preoperative Uu test by analyzing the correlation between the results of Uu culture before IVF-ET and the outcomes of IVF-ET. METHODS: Among 1,059 couples undergoing IVF-ET, we selected 973 after excluding genetic factors and divided them into a Uu negative and a Uu positive group according to the results of culture of Uu in the semen of the males. We compared the rates of IVF fertilization, oocyte cleavage, clinical pregnancy and abortion between the two groups, and analyzed the influence of Uu infection on IVF outcomes. RESULTS: Among the 973 selected subjects, 836 were Uu negative (group A) and 137 Uu positive (group B), and of the latter, 130 were restored to Uu negative after treatment (group B1) and the other 7 remained unchanged (group B2). No significant differences were found between groups A and B in the rates of IVF fertilization (81.6% vs 79.8%, P = 0.13), abnormal fertilization (11.8% vs 12.4%, P = 0.58) and oocyte cleavage (92.0% vs 92.1%, P = 0.94), nor between groups A and B2 (81.6% vs 89.8%, P = 0.10; 11.8% vs 13.2%, P = 0.75; 92.0% vs 92.5%, P = 0.10). Totally, 747 of the patients underwent embryo transfer, including 643 in group A and 104 in group B. There were no significant differences between groups A and B in the rates of clinical pregnancy (38.6% vs 34.7%, P = 0.44) and abortion (16.5% vs 22.2%, P = 0.39), nor between groups A and B2 (38.6% vs 33.3%, P = 0.79; 16.5% vs 0, P = 0.53). CONCLUSION: Uu infection in the male reproductive tract does not significantly affect the rates of IVF fertilization, oocyte cleavage, clinical pregnancy and abortion. However, more investigations with larger sample sizes of the cases restored from Uu positive to Uu negative are needed to lend further support to our findings.

The effects and mechanisms of AM1241 in alleviating cerebral ischemia-reperfusion injury.

OBJECTIVE: Research has shown that cerebral ischemia-reperfusion injury (CIRI) involves a series of physiological and pathological mechanisms, including inflammation, oxidative stress, and cell apoptosis. The cannabinoid receptor 2 agonist AM1241 has been found to have anti-inflammatory and anti-oxidative stress effects. However, it is unclear whether AM1241 has a protective effect against brain ischemia-reperfusion injury, and its underlying mechanisms are not yet known. METHODS: In this study, we investigated the anti-inflammatory, anti-oxidative stress, and anti-apoptotic effects of AM1241 and its mechanisms in BV2 cells stimulated with H2O2 and in a C57BL/6 mouse model of CIRI in vitro and in vivo, respectively. RESULTS: In vitro, AM1241 significantly inhibited the release of pro-inflammatory cytokines TNF-α and IL-6, reactive oxygen species (ROS), and the increase in Toll-like receptor 4/myeloid differentiation protein 2 (MD2/TLR4) complex induced by H2O2. Under H2O2 stimulation, MD2 overexpression resulted in increased levels of MD2/TLR4 complex, TNF-α, IL-6, NOX2, BAX, and Cleaved-Caspase3 (C-Caspase3), as well as the activation of the MAPK pathway and NF-κB, which were reversed by AM1241. In addition, molecular docking experiments showed that AM1241 directly interacted with MD2. Surface Plasmon Resonance (SPR) experiments further confirmed the binding of AM1241 to MD2. In vivo, AM1241 significantly attenuated neurofunctional impairment, brain edema, increased infarct volume, oxidative stress levels, and neuronal apoptosis in CIRI mice overexpressing MD2. CONCLUSION: Our study demonstrates for the first time that AM1241 alleviates mouse CIRI by inhibiting the MD2/TLR4 complex, exerting anti-inflammatory, anti-oxidative stress and anti-apoptotic effects.

Human cytomegalovirus UL23 exploits PD-L1 inhibitory signaling pathway to evade T cell-mediated cytotoxicity.

Human cytomegalovirus (HCMV), a widely prevalent human beta-herpesvirus, establishes lifelong persistence in the host following primary infection. In healthy individuals, the virus is effectively controlled by HCMV-specific T cells and typically exhibits asymptomatic. The T cell immune response plays a pivotal role in combating HCMV infection, while HCMV employs various strategies to counteract it within the host. Previously, we reported that UL23, a tegument protein of HCMV, facilitates viral immune evasion from interferon-gamma (IFN-γ) responses, and it is well known that IFN-γ is mainly derived from T cells. However, the involvement of UL23 in viral immune evasion from T cell-mediated immunity remains unclear. Herein, we present compelling evidence that UL23 significantly enhances viral resistance against T cell-mediated cytotoxicity during HCMV infection from the co-culture assays of HCMV-infected cells with T cells. We found that IFN-γ plays a major role in regulating T cell cytotoxicity mediated by UL23. More interestingly, we demonstrated that UL23 not only regulates the IFN-γ downstream responses but also modulates the IFN-γ secretion by regulating T cell activities. Further experiments indicate that UL23 upregulates the expression and signaling of programmed death ligand 1 (PD-L1), which is responsible for inhibiting multiple aspects of T cell activities, including activation, apoptosis, and IFN-γ secretion, as determined through RNA-seq analysis and inhibitor-blocking experiments, ultimately facilitating viral replication and spread. Our findings highlight the potential role of UL23 as an alternative antagonist in suppressing T cell cytotoxicity and unveil a novel strategy for HCMV to evade T cell immunity. IMPORTANCE: T cell immunity is pivotal in controlling primary human cytomegalovirus (HCMV) infection, restricting periodic reactivation, and preventing HCMV-associated diseases. Despite inducing a robust T cell immune response, HCMV has developed sophisticated immune evasion mechanisms that specifically target T cell responses. Although numerous studies have been conducted on HCMV-specific T cells, the primary focus has been on the impact of HCMV on T cell recognition via major histocompatibility complex molecules. Our studies show for the first time that HCMV exploits the programmed death ligand 1 (PD-L1) inhibitory signaling pathway to evade T cell immunity by modulating the activities of T cells and thereby blocking the secretion of IFN-γ, which is directly mediated by HCMV-encoded tegument protein UL23. While PD-L1 has been extensively studied in the context of tumors and viruses, its involvement in HCMV infection and viral immune evasion is rarely reported. We observed an upregulation of PD-L1 in normal cells during HCMV infection and provided strong evidence supporting its critical role in UL23-induced inhibition of T cell-mediated cytotoxicity. The novel strategy employed by HCMV to manipulate the inhibitory signaling pathway of T cell immune activation for viral evasion through its encoded protein offers valuable insights for the understanding of HCMV-mediated T cell immunomodulation and developing innovative antiviral treatment strategies.

Knockdown of LAMB3 suppressed radioresistance in nasopharyngeal carcinoma via deactivating NRF2 signaling pathway.

Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia and Southern China. Laminin subunit beta-3 (LAMB3) has been validated to participate in diverse cancers. Nevertheless, the role and mechanism of LAMB3 in NPC remain unclear. In this study, LAMB3 expression is upregulated in NPC cells and tissues. Interestingly, knockdown of LAMB3 promoted apoptosis and reduced the radioresistance of NPC cells. Besides, shLAMB3 enhanced X-ray-induced reactive oxygen species (ROS) accumulation. Mechanically, knockdown of LAMB3 deactivated nuclear factor erythroid-2-related factor 2 (NRF2) signaling pathway via enhancing forkhead box 3 (FOXO3) expression. In rescue experiments, suppression of NRF2 signaling pathway abrogated shLAMB3-induced NPC cell apoptosis and ROS accumulation under X-ray treatment. Similarly, LAMB3 knockdown restrains NPC tumor growth and reduces radioresistance in vivo. Thus, these findings concluded that knockdown of LAMB3 enhanced apoptosis and ROS accumulation, and suppressed radioresistance in NPC via enhancing FOXO3 expression and deactivating NRF2 signaling pathway, facilitating the development of novel strategies for NPC radioresistance.

Classification and Pathological Diagnosis of Idiopathic Interstitial Pneumonia.

Idiopathic interstitial pneumonia (IIP) is a group of progressive lower respiratory tract diseases of unknown origin characterized by diffuse alveolitis and alveolar structural disorders leading to pulmonary fibrillation and hypertension, pulmonary heart disease, and right heart failure due to pulmonary fibrosis, and more than half of them die from respiratory failure. To address these problems of overly complex prediction methods and large data sets involved in the prediction process of interstitial pneumonia, this paper proposes a prediction model for interstitial pneumonia which is based on the Gaussian Parsimonious Bayes algorithm. Three usual tests of pneumonia, specifically from various patients, were collected as the sample set. These samples are divided into training and testing sets. Additionally, a cross-validation strategy was used to avoid the overfitting problem. The results showed that the prediction model based on the Gaussian Parsimonious Bayes algorithm predicted 92% accuracy on the test set, and the Parsimonious Bayes method could directly predict the final detection of interstitial pneumonia based on the usual pneumonia test pneumonia. In addition, it was found that the closer the data distribution of the sample set was to a normal distribution, the higher the prediction accuracy was, and then, after excluding pneumonia from the test below 60 points, the prediction accuracy reached 96%.

Anticipatory threat responses mediate the relationship between mindfulness and anxiety: A cross-sectional study.

Increasing research has shown that mindfulness-based interventions can effectively alleviate anxiety; however, the underlying neural mechanism has not yet been elucidated. Recent studies suggest that abnormal and excessive anticipatory responses to unpredictable threats play an important role in anxiety symptoms. Mindfulness refers to the non-judgmental awareness of the present moment's real experience, which is antithetical to the future-oriented thinking processes involved in anxiety-oriented cognition and its corresponding emotion regulation tactics. Thus, mitigating anticipatory threat responses may be a potential mechanism by which mindfulness alleviates anxiety. This study aimed to detect the possible mediating effects of anticipatory threat responses on the relationship between mindfulness and anxiety. A total of 35 trait-anxious (TA) individuals and 36 low-anxious (LA) individuals were recruited to participate in the predictable and unpredictable threat test. Self-reported intolerance of uncertainty (IU) and electroencephalographic responses to uncertainty were recorded. TA individuals reported more IU and less mindfulness, and exhibited significantly higher late positive potential (LPP) and longer reaction time (RT) than LA individuals in the unpredictable negative threat condition. In addition, there were significant mediating effects of the LPP amplitude and RT in the uncertain threats on the relationship between mindfulness and anxiety. The data from this study verified that mitigating anticipatory threat responses (including self-reported IU, behavioral RT, and LPP amplitude) might be the potential mechanism by which mindfulness alleviates anxiety. These findings may have practical implications for the development and optimization of mindfulness treatments for anxiety.

Effect of HAc on the Metastable Pitting Corrosion of 304 SS in NaCl Solution.

Stainless steels (SSs) easily suffer localized corrosion damage, such as pitting corrosion, in mixed solutions of acetic acid and sodium chloride. Currently, few works have been focused on the early stages of the pitting corrosion (metastable pitting corrosion) process of SSs in a chloride-HAc mixture solution. In this work, the effects of acetic acid (HAc) and its concentration on metastable pitting corrosion and the uniform corrosion of 304 SS in 0.6 mol/L NaCl solution were investigated by a slow-scanning potentiodynamic polarization test, scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). The results show that the uniform corrosion rate of 304 SS increases after HAc addition but, with an increase in HAc concentration, the corrosion rate decreases. In the presence of HAc, the metastable pitting potential (Em) and stable pitting potential (Eb) move negatively, but the number of metastable pits notably decreases. HAc has a promoting action on the growth rate of the metastable pits and facilitates the transition from metastable pits to stable pits. The influence of HAc is related to a decrease in solution pH and the chemical adsorption of HAc.

Increased FOXA1 levels induce apoptosis and inhibit proliferation in FOXA1-low expressing basal breast cancer cells.

The transcription factor FOXA1, which is a member of the forkhead class of DNA-binding proteins, interacts with Estrogen Receptor (ER) to mediate breast cancer progression. However, its role in basal breast cancer cells remains unclear. Although the overall levels of FOXA1 are decreased in the basal subtype of clinical TCGA breast cancer samples, the high levels of FOXA1 improve the survival of the patients from this subtype. This clinical phenomenon is consistent with that of FOXA1 stimulating apoptosis in FOXA1-low expressing basal breast cancer cells, such as MDA-MB-231, and MDA-MB-468 cells. In this study, we have constructed an inducible expression system of FOXA1 and demonstrated the induced expression of FOXA1 resulting in apoptosis and cell cycle arrest in MDA-MB-231 cells, as confirmed by transcriptomic analysis and in vivo tumor-grafted models. Furthermore, the low levels of Estrogen Receptor-1 (ESR1) are critical for FOXA1 in terms of its repressive roles in the cells, as evidenced by clinical data analysis indicating that the high levels of FOXA1 improve the survival of ESR1Low patients, but worsen the survival of ESR1High patients of breast cancer. When introduced into MDA-MB-231 cells, ESR1 counteracts the tumor suppressor roles of FOXA1 by altering the FOXA1-regulated gene transcription and the two proteins together maintain the tumor progression in vivo. Our cumulative results suggest that FOXA1 suppresses the basal breast cancer cells with FOXA1-low expressing status independent of ESR1 by inducing apoptosis and inhibiting cell proliferation, thereby implicating its potential therapeutic role in this group of breast cancer.

The Reactive Astrocytes After Surgical Brain Injury Potentiates the Migration, Invasion, and Angiogenesis of C6 Glioma.

BACKGROUND: Surgical resection is a key method for glioma treatment. This inherently invasive procedure alters the tumor microenvironment of glioma cells that cannot be removed by surgery. However, few studies have focused on the impact of this microenvironment change on the growth of glioma cells. METHODS: The authors preconstructed a surgical brain injury model, and then C6 glioma cells were transplanted. HE staining was used to observe the general morphology of tumor cells, and immunohistochemistry of MMP-2, MMP-9, GFAP, and CD31 was used to evaluate the invasiveness of glioma cells and activation of astrocytes and calculate microvessel density. In vitro, primary rat astrocytes were exposed to different temperature gradients. The supernatant was made into conditioned medium for culturing C6 glioma cells. The scratch test and transwell test were used to evaluate the migration and invasion of tumor cells. RESULTS: GFAP expression was stronger in surgical brain injury rats, C6 cells implanted in these rats showed stronger expression of MMP-2 and MMP-9, and CD31 was expressed in more microvessels. Astrocytes exposed to high temperatures of 40°C and 43°C expressed stronger GFAP, and C6 cells cultured in their supernatants had stronger scratch healing ability and the ability to cross transwell chambers. CONCLUSIONS: The microenvironment changes caused by surgical brain injury will enhance the migration and invasion of glioma cells and increase the microvessel density in the tumor. This effect may be related to the activation of astrocytes caused by the thermal injury of bipolar coagulation during surgery.

Sensory Description and Consumer Hedonic Perception of Ultra-High Temperature (UHT) Milk.

Sensory characteristics of products play an essential role on the consumer' s acceptability, preference and consuming behavior choice. The sensory profiles and consumer hedonic perception for 14 UHT milk products using sensory quantitatively descriptive analysis and a 9-point hedonic scale were investigated in this study. There were significant differences in the sensory attributes intensity and liking scores among the organic whole milk, ordinary whole milk, low-fat milk, and skimmed milk (p < 0.05). Skimmed milk samples had lowest intensity scores of typical milk aroma, taste flavor and texture attributes, as well as had the lowest overall liking scores. Whole milk samples had higher sensory intensity scores than low-fat milk samples, even though no significant differences of overall liking scores were observed between whole milk and low-fat milk. Furthermore, the relationship between the sensory attribute and overall liking was demonstrated according to correlation analysis and partial least squares regression (PLSR) analysis. Overall liking increased significantly with the increasing of sweet, after milk aroma, protein-like, mellow and thick, while decreased significantly with the enhancement of cowy, cooked and whey (p < 0.05). These findings presented a potential strategy for identifying the key sensory attributes responsible for liking score differences among different kinds of UHT milk products.

Preparation of gastrodin-modified dendrimer-entrapped gold nanoparticles as a drug delivery system for cerebral ischemia-reperfusion injury.

OBJECTIVE: This study sought to evaluate the feasibility of multifunctional gastrodin (GAS)-containing nano-drug carrier system against cerebral ischemia-reperfusion injury (CIRI). METHODS: The drug-loaded nanocomposite (Au-G5.NHAc-PS/GAS) with certain encapsulation efficiency (EE) was prepared by physical adsorption method using different proportions of GAS and drug-carrying system (Au-G5.NHAc-PS). High-performance liquid chromatography was used to determine the drug loading and EE. Cultured rat astrocytes and hypothalamic neurons were assigned into four groups: PBS, Au-G5.NHAc-PS, Au-G5.NHAc-PS/GAS, and GAS. CCK-8 assay, flow cytometry, and quantitative real-time PCR were performed to examine the cell viability, apoptosis, and the expression of tumor necrosis factor-α (TNF-α), IL-1ß, and IL-6 in the astrocytes and hypothalamic neurons, respectively. Cellular uptake of GAS and Au-G5.NHAc-PS/GAS was analyzed by using Hoechst 33342 staining. The animal model with focal cerebral ischemia was generated by middle cerebral artery occlusion (MCAO) in healthy male Sprague Dawley (SD) rats, and pathological changes of brain tissue and major organs in the rats were identified by hematoxylin and eosin (HE) staining. Apoptosis in rat astrocytes and hypothalamic neurons was detected by TUNEL staining and flow cytometry. RESULTS: Au-G5.NHAc-PS had a spherical shape with a uniform size of 157.3 nm. Among the nanoparticles, Au-G5.NHAc-PS/GAS with an EE of 70.3% displayed the best release delay effect. Moreover, we observed that in vitro cytotoxicity and cellular uptake of Au-G5.NHAc-PS/GAS were higher than those of GAS, whereas the expression of TNF-α, IL-1ß, and IL-6 was significantly downregulated in Au-G5.NHAc-PS/GAS group as compared to G5.NHAc-PS group. Notably, HE staining revealed that although Au-G5.NHAc-PS/GAS had no toxic and side effects on the main organs of rats, it alleviated the damage of brain tissue in the MCAO rats. Besides, Au-G5.NHAc/GAS markedly reduced MCAO-induced apoptosis. CONCLUSION: Au-G5.NHAc-PS showed favorable surface morphology, sustained drug release ability, no measurable toxicity, and good biocompatibility, indicating that GAS exerts anti-inflammatory and antiapoptotic effects on CIRI.

Impact of short-term exposure to extreme temperatures on diabetes mellitus morbidity and mortality? A systematic review and meta-analysis.

The relationship between diabetes mellitus and short-term exposure to extreme temperatures remains controversial. A systematic review and meta-analysis were performed to assess the association between extreme temperatures and diabetes mellitus morbidity and mortality. PubMed, Embase, the Cochrane Library, Web of Science, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched since inception to January 1, 2019, and updated on November 17, 2020. The results were combined using random effects model and reported as relative risk (RR) with 95% confidence interval (CI). In total, 32 studies met the inclusion criteria. (1) Both heat and cold exposures have impact on diabetes. (2) For heat exposure, the subgroup analysis revealed that the effect on diabetes mortality (RR=1.139, 95% CI: 1.089-1.192) was higher than morbidity (RR=1.012, 95% CI: 1.004-1.019). (3) With the increase of definition threshold, the impact of heat exposure on diabetes rose. (4) A stronger association between heat exposure and diabetes was observed in the elderly (≥ 60 years old) (RR=1.040, 95% CI: 1.017-1.064). In conclusion, short-term exposure to both heat and cold temperatures has impact on diabetes. The elderly is the vulnerable population of diabetes exposure to heat temperature. Developing definitions of heatwaves at the regional level are suggested.

Genetic evolution of equine influenza viruses isolated in China.

China experienced an outbreak of equine influenza during 2007-2008. Meanwhile, its neighbor countries, such as Mongolia, India and Japan, have also been affected by various influenza virus strains in each country. Phylogenetic analysis showed that the newly emerging Chinese strains belong to Florida sublineage clade 2, as well as the Indian strain Jammu-Katra/6/08 and the Mongolian strain Mongolia/1/08. All of these strains were derived from European strains of this clade, such as the Newmarket/1/07 and Cheshire/1/07 strains, but these were not related to Japanese strains isolated around the same time (Florida sublineage clade 1) or to Chinese strains isolated in the 1990s (European lineage). Some unique amino acid changes were found in the antigenic sites in Asian strains of Florida sublineage clade 2. Moreover, the loss of a glycosylation site was found in the Liaoning/9/08 strain. From these studies, we have determined that equine influenza viruses in China have evolved with some new characteristics during recent years, and this emphasizes the importance of continued equine influenza virus surveillance in China.

Hippocampal Ripple Coordinates Retrosplenial Inhibitory Neurons during Slow-Wave Sleep.

The hippocampus and retrosplenial cortex (RSC) play indispensable roles in memory formation, and importantly, a hippocampal oscillation known as ripple is key to consolidation of new memories. However, it remains unclear how the hippocampus and RSC communicate and the role of ripple oscillation in coordinating the activity between these two brain regions. Here, we record from the dorsal hippocampus and RSC simultaneously in freely behaving mice during sleep and reveal that the RSC displays a pre-ripple activation associated with slow and fast oscillations. Immediately after ripples, a subpopulation of RSC putative inhibitory neurons increases firing activity, while most RSC putative excitatory neurons decrease activity. Consistently, optogenetic stimulation of this hippocampus-RSC pathway activates and suppresses RSC putative inhibitory and excitatory neurons, respectively. These results suggest that the dorsal hippocampus mainly inhibits RSC activity via its direct innervation of RSC inhibitory neurons, which overshadows the RSC in supporting learning and memory functions.

[Distribution of ABO blood group in Tibetan population and their genetic relationship].

OBJECTIVE: To explore the distribution of ABO blood group in Tibetans population and their genetic relationship. METHODS: Data of ABO blood group of 28 Tibetan populations were collected from China and India. The gene frequencies were processed by Phylip3.68 and MEGA4.1 genetic analysis software pack, and the Nei's genetic distance was imported and the genetic relationship was analyzed. RESULTS: The distribution of ABO blood group among Gansu, Qianghai, Sichuan, Yunnan, Tibet, and India was O>A>B>AB. The nation index and genetic distance were 0.63-0.98 and 0-0.0072, respectively. CONCLUSION: There is probable historical relationship among the ancestors of these Tibetan populations, but the differentiation incident of Tibetan population living in different area in history was different, so that their distribution of gene frequencies is diversified.