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Vehicle exhaust (VE) is the primary cause of urban air pollution, which adversely affects the respiratory system, exacerbates lung diseases, and results in high mortality rates. However, the underlying mechanism of the pathogenesis is largely unclear. Here, we developed a Drosophila model to systematically investigate the effects of VE on their health and physiology. We found that VE significantly impaired life span and locomotion in Drosophila. Interestingly, there was an increase in bacterial load in the guts upon VE exposure, suggesting VE is able to induce dysbiosis in the guts. Microbiota depletion can ameliorate the impairment of life span and locomotion. VE causes permeability of intestinal epithelial cells and increases proliferation of intestinal cells, suggesting VE disrupts intestinal homeostasis. We elucidate the underlying mechanism by which VE triggers Imd and DUOX gene expression. Taken together, this Drosophila model provides insight into the pathogenesis of Drosophila exposure to VE, enabling us to better understand the specific role of microbiota.

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BACKGROUND: Hypoxic pulmonary hypertension (HPH) is a common type of pulmonary hypertension and characterized by pulmonary vascular remodeling and constriction. Alveolar epithelial cells (AECs) primarily sense alveolar hypoxia, but the role of AECs in HPH remains unclear. In this study, we explored whether AECs are involved in pulmonary vascular remodeling and constriction. METHODS: In the constructed rat HPH model, hemodynamic and morphological characteristics were measured. By treating AECs with hypoxia, we further detected the levels of superoxide dismutase 2 (SOD2), catalase (CAT), reactive oxygen species (ROS) and hydrogen peroxide (H2O2), respectively. To detect the effects of AECs on pulmonary vascular remodeling and constriction, AECs and pulmonary artery smooth cells (PASMCs) were co-cultured under hypoxia, and PASMCs and isolated pulmonary artery (PA) were treated with AECs hypoxic culture medium. In addition, to explore the mechanism of AECs on pulmonary vascular remodeling and constriction, ROS inhibitor N-acetylcysteine (NAC) was used. RESULTS: Hypoxia caused pulmonary vascular remodeling and increased pulmonary artery pressure, but had little effect on non-pulmonary vessels in vivo. Meanwhile, in vitro, hypoxia promoted the imbalance of SOD2 and CAT in AECs, leading to increased ROS and hydrogen peroxide (H2O2) production in the AECs culture medium. In addition, AECs caused the proliferation of co-cultured PASMCs under hypoxia, and the hypoxic culture medium of AECs enhanced the constriction of isolated PA. However, treatment with ROS inhibitor NAC effectively alleviated the above effects. CONCLUSION: The findings of present study demonstrated that AECs were involved in pulmonary vascular remodeling and constriction under hypoxia by paracrine H2O2 into the pulmonary vascular microenvironment.

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BACKGROUND: The novel coronavirus disease 2019 (COVID-19) is an emerging worldwide threat to public health. While chest computed tomography (CT) plays an indispensable role in its diagnosis, the quantification and localization of lesions cannot be accurately assessed manually. We employed deep learning-based software to aid in detection, localization and quantification of COVID-19 pneumonia. METHODS: A total of 2460 RT-PCR tested SARS-CoV-2-positive patients (1250 men and 1210 women; mean age, 57.7 ± 14.0 years (age range, 11-93 years) were retrospectively identified from Huoshenshan Hospital in Wuhan from February 11 to March 16, 2020. Basic clinical characteristics were reviewed. The uAI Intelligent Assistant Analysis System was used to assess the CT scans. RESULTS: CT scans of 2215 patients (90%) showed multiple lesions of which 36 (1%) and 50 patients (2%) had left and right lung infections, respectively (> 50% of each affected lung's volume), while 27 (1%) had total lung infection (> 50% of the total volume of both lungs). Overall, 298 (12%), 778 (32%) and 1300 (53%) patients exhibited pure ground glass opacities (GGOs), GGOs with sub-solid lesions and GGOs with both sub-solid and solid lesions, respectively. Moreover, 2305 (94%) and 71 (3%) patients presented primarily with GGOs and sub-solid lesions, respectively. Elderly patients (≥ 60 years) were more likely to exhibit sub-solid lesions. The generalized linear mixed model showed that the dorsal segment of the right lower lobe was the favoured site of COVID-19 pneumonia. CONCLUSION: Chest CT combined with analysis by the uAI Intelligent Assistant Analysis System can accurately evaluate pneumonia in COVID-19 patients.

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BACKGROUND: During the bronchoscopy process, successful passage of the tracheoscope through the glottis can affect the following procedure of bronchoscopy. Therefore, safer, more effective and less painful anesthesia methods are particularly important for the bronchoscopy success rate. OBJECTIVE: This study aimed to evaluate the efficacy of 1% tetracaine hydrochloride injection pure solution aerosol inhalation combined with oral administration of dyclonine hydrochloride mucilage during bronchoscopy. METHODS: Patients who need bronchoscopy or bronchoscope treatment were randomly assigned to two groups; group A received pure tetracaine hydrochloride injection solution (3 mL of 1% tetracaine hydrochloride) aerosol inhalation combined with oral 5 mL of dyclonine hydrochloride mucilage and group B received diluted tetracaine hydrochloride injection (3 mL of 1% tetracaine hydrochloride injection + 3 mL of sterile water for injection) aerosol inhalation combined with oral 5 mL of dyclonine hydrochloride mucilage. The anesthetic effect and adverse reactions of these groups were observed and compared. RESULT: A total of 523 patients were randomized. The results showed that patient's tolerance, cough response, glottis opening during the bronchoscope into the glottis and the time required to the tracheoscope pass through the glottis were obviously significantly better in group A than in group B. Vital signs including blood pressure, heart rate and pulse oxygen saturation were more stable in group A than in group B. CONCLUSION: The 1% tetracaine hydrochloride injection pure liquid aerosol inhalation combined with oral administration of dyclonine hydrochloride mucilage as upper airway anesthesia is effective and safe for bronchoscopy. This method of local anesthesia is worthy of clinical application.

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Substantial evidence has demonstrated that prenatal stress (PS) impairs spatial learning and memory in offspring. The neuron-specific protein kinase C gamma (PKCγ) has been proposed to be unique in spatial learning and memory. The present study proposes to determine whether hippocampal PKCγ is involved in the detrimental effects of PS on spatial learning and memory in offspring, and to further explore the effects of PS-induced PKCγ-dependent growth-associated protein 43 (GAP-43) and neurogranin (Ng) phosphorylation alteration on calcium/calmodulin-dependent protein kinase II (CaMKII) activation. Prenatal restraint stress models were established, and lentivirus-mediated overexpression of PKCγ in the hippocampal CA1 area was applied. The results demonstrated that PS impaired spatial learning acquisition and memory retrieval on the Morris Water Maze test, especially in juvenile female rats. Hippocampal PKCγ membrane translocation and cytosolic PKCγ levels were decreased in PS females. The expression of phosphorylated GAP-43 (p-GAP-43) and phosphorylated Ng (p-Ng), as well as phosphorylated CaMKII (p-CaMKII), was significantly reduced in the hippocampus of PS females. Overexpression of PKCγ in the hippocampal CA1 area recovered the ability of spatial learning and memory in PS female offspring. Furthermore, enhancing PKCγ reversed PS-induced membrane and cytosolic PKCγ reduction, and restored levels of GAP-43 and Ng phosphorylation, and CaMKII activation in the hippocampus. In conclusion, PS possibly decreases hippocampal PKCγ activity, resulting in a reduction of p-GAP-43 and p-Ng, which underlies insufficient CaMKII activation, thereby impairing spatial learning and memory.

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Particulate matter 2.5 (PM2.5) exposures during pregnancy could lead to declined birth weight, intrauterine developmental restriction, and premature delivery, however, the underlying mechanisms are still not elucidated. There are few studies concerning the effects of PM2.5 exposure on maternal and child health in Xi'an (one of the cities with severe air pollution of PM2.5 in North China). Then, this study aimed to investigate the effect of PM2.5 exposure in Xi'an on the offspring birth weights and the possibly associated epigenetic mechanisms. We found the Low and High groups: the offspring with declined birth weights; the decreased mRNA and protein expression of the estrogen receptor (ERs) and eNOs in the uterus; the decreased endometria vascular diameter maximum (EVDM); the increased mRNA and protein expressions of the DNMT1 and 3b in the uterus; the elevated methylation levels of the CpG sites in the CpG island of ERα promoter region in the uterus. However, no differences were observed in the mRNA or protein expressions of ERß and DNMT3a between the Clean and PM2.5 exposure groups, as well as endometriavascular density (EVD). Additionally, PM2.5 level was negatively correlated with the ERα protein expression, EVDM and offspring birth weight, as well as the methylation level of the CpG sites in the CpG island of ERα promoter region and the ERα protein expression in the uterus; whereas the ERα protein expression was positively correlated with the offspring birth weight, as well as PM2.5 level and the methylation level of the CpG sites in the CpG island of ERα promoter region in the uterus. Taken together, elevated methylation level of the CpG sites in the CpG island of ERα promoter region reduces ERα expression in the uterus, which could be one of the epigenetic mechanisms that pregnant PM2.5 exposure reduces the offspring birth weights.

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An increasing number of epidemiological investigations and animal models research suggest that prenatal stress (PS) could cause depression-like behavior in the offspring, which is sex specific. However, the underlying mechanisms remain to be elucidated. This study is to investigate the promoter methylation of metabotropic glutamate receptor 1 (mGluR1) and metabotropic Glutamate Receptor 5 (mGluR5) gene modification on PS induced depression-like behavior in offspring rats (OR). PS models were established, with or without 5-aza-2′-deoxycytidine (5-azaD, decitabine) treatment. Animal behavior was assessed by the sucrose preference test (SPT), forced swimming test (FST), and open field test (OFT). The mRNA and protein expression levels of mGluR1 and mGluR5 in the hippocampus of offspring were detected with quantitative real-time PCR and Western blot analysis, respectively. The promoter methylation in the hippocampus of mGluR1 and mGluR5 OR were also analyzed. SPT showed significantly reduced sucrose preference in PS induced OR. FST showed significantly prolonged immobility time in PS induced OR. OFT showed significantly reduced central residence time in PS induced OR and no significantly influence in rearing as well as in frequency of micturition. Moreover, the mRNA, protein expression levels, and gene promoter methylation level of mGluR1 and mGluR5 in the hippocampus were significantly increased in the PS induced male OR, while no significantly influence in the PS induced female OR. Furthermore, the PS induced effects in male OR could be reversed by the microinjection of 5-azaD. In conclusion, our results showed that the promoter methylation of mGluR1 and mGluR5 gene modification is only involved in PS induced depression-like behavior in male OR in a sex-specific manner. These findings might contribute to the understanding of the disease pathogenesis and clinical treatment in future.

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BACKGROUND: Newborn irritability could be an unique and special status and/or adverse neurobehavioral outcomes which was independent of serious disease. To determine whether maternal perinatal anxiety symptoms was associated with newborn irritability, and whether the alteration of serum prolactin in newborns were involved in newborn irritability. METHODS: 205 pregnant women were recruited: normal group (n = 100), and anxiety group (n = 105), which was randomly divided to Newborn Behavioral Observations (NBO)+anxiety group(n = 65) and control+anxiety group(n = 40). Newborn Irritability was assessed by Neonatal Behavioral Assessment Scale(NBAS). Serum prolactin, cortisol and 5-HT in mothers and infants were measured. RESULTS: 1. The scores of irritability items in the newborns of anxiety group were higher than that of the normal group (p < 0.05). 2. Lower serum PRL, 5-HT and higher serum cortisol were found in the newborns of anxiety group compared with that of the control group both postpartum 2d and 15 (p < 0.05). 3. The level of serum PRL in newborn infants were significantly and negatively correlated to the scores of irritability items (p < 0.05). 4. After 7 rounds of NBO interventions, the anxiety scores of mothers and the scores of irritability items of newborns in the NBO intervention group were all lower than those of the control group (p < 0.05) . LIMITATIONS: In future experiments, we should explore the effect of PRL in the breast milk on newborn infant serum PRL. CONCLUSIONS: Prolactin could be a potential mediator in newborn irritability following maternal perinatal anxiety symptoms.

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Increasing evidence has shown that prenatal stress (PS) could cause depression-like behavior in the offspring, which is sex-specific. However, the underlying mechanisms remain to be elucidated. This study is to investigate the involvement of tryptophan hydroxylase 2 (Tph2) H3K9 acetylation (H3K9ac) modification on PS-induced depression-like behavior in juvenile offspring rats (JOR). PS models were established, with or without trichostatin A (TSA) treatment. Animal behavior was assessed by the sucrose preference test (SPT) and forced swimming test (FST). The mRNA and protein expression levels of TPH2 in the dorsal raphenucleus (DRN), hippocampus, and prefrontal cortex were detected with quantitative real-time PCR and Western blot analysis, respectively. The Tph2 H3K9ac levels in the hippocampus were also analyzed. SPT and FST showed significantly reduced sucrose preference and significantly prolonged immobility in PS-induced male juvenile offspring rats (MJOR). Moreover, the mRNA and protein expression levels of TPH2 in the DRN and hippocampus were significantly declined, while the hippocampal Tph2 H3K9ac levels were significantly declined in the PS-induced MJOR. Furthermore, the PS-induced effects in MJOR could be reversed by the microinjection of TSA. However, no significant effects were observed for the female juvenile offspring rats (FJORs). In conclusion, our results showed that the Tph2 H3K9ac modification is only involved in PS-induced depression-like behavior in MJOR, in a sex-specific manner. These findings might contribute to the understanding of the disease pathogenesis and clinical treatment in future.

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Ghrelin is a peptide hormone that plays an important role in promoting appetite, regulating distribution and rate of use of energy, cognition, and mood disorders, but the relevant neural mechanisms of these function are still not clear. In this study, we examined the effect of ghrelin on voltage-dependent potassium (K+) currents in hippocampal cells of 1-3 days SD rats by whole-cell patch-clamp technique, and discussed whether NO was involved in this process. The results showed that ghrelin significantly inhibited the voltage-dependent K+ currents in hippocampal cells, and the inhibitory effect was more significant when l-arginine was co-administered. In contrast, N-nitro- l-arginine methyl ester increased the ghrelin inhibited K+ currents and attenuated the inhibitory effect of ghrelin. While d-arginine (D-AA) showed no significant impact on the ghrelin-induced decrease in K+ current. These results show that ghrelin may play a physiological role by inhibiting hippocampal voltage dependent K+ currents, and the NO pathway may be involved in this process.

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This study is to determine the role and mechanism of hippocampal acetylation in prenatal stress (PS) induced depression-like behavior of male offspring rats. PS-induced depression rat model was established. Sucrose preference and forced swim test were used to observe the behavior changes of male offspring rats. Hippocampal acetylation was induced by Trichostatin A injection. Quantitative real-time PCR and Western blot were used to determine the changes of AMPARs in acetylated hippocampus. The behavioral tests proved that AMPA was involved in the PS-induced depression-like behavior in offspring rats. Hippocampal acetylation significantly increased the preference to sucrose of PS-induced offspring rats and reduced the immobile time in forced swimming test, suggesting that acetylation could improve PS-induced depression-like behaviors. In addition, PS inhibited the expression levels of GluA1-3 subunits of AMPARs in the offspring hippocampus, while Hippocampal acetylation could reverse this effect by increasing GluA1-3 expression. PS-induced reduction of GluA1-3 subunits of AMPARs may be an important potential mechanism of offspring depression. Hippocampal acetylation may improve PS-induced offspring depression-like behavior through the enhanced expression of AMPARs (GluA1-3 subunits).

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OBJECTIVE: The present study was performed to identify antidepressant-like activity of icariin in prenatally stressed male rats. METHODS: The effects of icariin on PRS-induced depression were examined using sucrose preference test (SPT) and forced swimming test (FST) in male offspring, and measuring protein and mRNA expressions of group I mGluRs receptors and EAAT2 via western blotting and quantitative real-time PCR assays. RESULTS: The results indicated that prenatal restraint stress (PRS) resulted in several behavioral anomalies. Treatment with icariin relieved the elevated protein and mRNA levels of group I mGluR receptors as well as the diminished protein and mRNA levels of EAAT2 in the PRS male offspring. CONCLUSIONS: Collectivity, the data support that icariin ameliorates PRS-induced depressive-like behavior via regulating expression of mGluR1, mGluR5 and EAAT2 in the hippocampus.

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BACKGROUND: The hormone prolactin (PRL) plays a crucial role for the initiation and maintenance of maternal behavior, and is also associated with the etiology of mood disorders in women, especially for depression. The present study aimed to determine whether maternal peripheral prolactin would be associated with newborn behavior disorders following maternal perinatal depressive symptoms, and further to explore the efficacy of the Newborn Behavioral Observations (NBO) in improving newborn social interactive behavior. METHODS: Interview and the 24-item Hamilton Rating Scale for Depression (HAMD) were used to assess the hospitalized pregnant women waiting for delivery at 37-42weeks of gestation. A total of 255 subjects were recruited, diagnosed with depression (n=135), and control group (n=120). Within 2 weeks postpartum, mothers were asked to fill with Maternal Attachment Inventory (MAI) to measure maternal care. Neonatal Behavioral Assessment Scale (NBAS) were used to evaluate newborn behavior. The depressed mother-newborns dyad was randomly assigned to NBO intervention and control group. Serum prolaction in mothers and cortisol in mothers and newborns were measured. RESULTS: The newborns of mothers exposed to maternal perinatal depressive symptoms displayed the reduced newborn social interactive behavior accompanied by decreased maternal serum PRL as well as increased maternal and neonatal serum cortisol. The NBO could be an effective intervention tool. LIMITATIONS: Our study could not be double-blind. The mothers knew which group their infant were in. CONCLUSIONS: Maternal peripheral PRL had the potential to be a mediator in reduced social interactive behavior in newborn infants following maternal perinatal depressive symptoms.

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Substantial evidence has shown that the oxidative damage to hippocampal neurons is associated with the cognitive impairment induced by adverse stimuli during gestation named prenatal stress (PS). Taurine, a conditionally essential amino acid, possesses multiple roles in the brain as a neuromodulator or antioxidant. In this study, to explore the roles of taurine in PS-induced learning and memory impairment, prenatal restraint stress was set up and Morris water maze (MWM) was employed for testing the cognitive function in the one-month-old rat offspring. The mitochondrial reactive oxygen species (ROS) level，mitochondrial membrane potential (MMP), ATP and cytochrome c oxidase (CcO) activity and apoptosis-related proteins in the hippocampus were detected. The activity of the Akt-cyclic AMP response element-binding protein (CREB)-peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) pathway in the hippocampus was measured. The results showed that high dosage of taurine administration in the early postnatal period attenuated impairment of spatial learning and memory induced by PS. Meanwhile, taurine administration diminished the increase in mitochondrial ROS, and recovered the reduction of MMP, ATP level and the activities of CcO, superoxide dismutase 2 (SOD2) and catalase induced by PS in the hippocampus. In addition, taurine administration recovered PS-suppressed SOD2 expression level. Taurine administration blocked PS-induced decrease in the ratio of Bcl-2/Bax and increase in the ratio of cleaved caspase-3/full-length caspase-3. Notably, taurine inhibited PS-decreased phosphorylation of Akt (pAkt) and phosphorylation of CREB (pCREB), which consequently enhanced the mRNA and protein levels of PGC1α. Taken together, these results suggest that high dosage of taurine administration during the early postnatal period can significantly improve the cognitive function in prenatally stressed juvenile rats via activating the Akt-CREB-PGC1α pathway. Therefore, taurine has therapeutic potential for prenatal stressed offspring rats in future.

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