Inhibition of Dorsal Root Ganglia Transient Receptor Potential Ankyrin 1 Upregulation Contributes to the Protective Effect of Morphine Against Gastric Mucosal Damage Induced by Water-Immersion Restraint Stress.

The pathogenesis mechanism of acute gastric mucosal lesions (AGML) is still unclear; further exploration is urgently needed to find a new therapeutic target. This study aimed to investigate whether morphine might regulate the expression and function of transient receptor potential ankyrin 1 (TRPA1) through a cyclic adenosine monophosphate/protein kinase A (cAMP/PKA)-dependent pathway, thereby alleviating gastric mucosal lesions caused by water-immersion restraint stress (WIRS). Rats were administered with intrathecal morphine, TRPA1 antagonist (HC-030031), µ-opioid receptor antagonist, or protein kinase A inhibitor (H-89), respectively, before WIRS. After 6 hours of WIRS, microscopic lesions, hematoxylin and eosin staining, and transmission electron microscopy were applied to assess the damage of the gastric mucosa. Real-time polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay were conducted to detect the levels of TRPA1 and substance P (SP) in the dorsal root ganglia (DRG) and gastric tissues. In addition, immunofluorescence was used to explore the possible co-expression of TRPA1 and µ-opioid receptors in the DRG. The results indicated that WIRS upregulated TRPA1 and SP in gastric mucosa, and HC-030031 or H-89 could alleviate gastric mucosal lesions caused by WIRS (P < .0001). Morphine was found to suppress both WIRS-induced gastric mucosal lesions (P < .0001) and the upregulation of TRPA1 (P = .0086) and SP (P = .0013). Both TRPA1 and SP play important roles in the pathogenesis of WIRS-induced AGML. Exogenous gastroprotective strategies reduce elevated levels of TRPA1 via the cAMP/PKA-dependent pathway. Inhibition of TRPA1 upregulation in the DRG is critical for intrathecal morphine preconditioning-induced gastric protection.

Familiar observers attenuate surgery-induced neuroinflammation and cognitive dysfunction in mice.

AIMS: Postoperative cognitive dysfunction (POCD) is a common complication associated with poor outcome. Our previous study has shown that living with familiar observers in the same cage reduces anxiety of mice with surgery. Anxiety can impair learning and memory. Thus, this study was designed to determine whether living with familiar observers attenuated the dysfunction of learning and memory of mice with surgery. METHODS: Six- to eight-week-old CD-1 male mice or 18-month-old C57BL/6 male mice had left carotid artery exposure under isoflurane anesthesia. They lived with non-surgery male mice at 2 (number of surgery mice) to 3 (number of non-surgery mice) ratio or with other surgery mice. Mice were subjected to light and dark box test 3 days after surgery to measure their anxiety levels and novel object recognition and fear conditioning tests from 5 days after surgery to measure their learning and memory. Blood and brain were harvested for biochemical analysis. RESULTS: Living with familiar observers that lived with surgery mice for at least 2 weeks before the surgery and then after surgery reduced the anxiety and dysfunction of learning and memory in young adult male mice. Living with unfamiliar observers that lived with surgery mice after the surgery but not before the surgery did not have those effects on the mice with surgery. Living with familiar observers attenuated learning and memory dysfunction after surgery also in old male mice. Living with familiar observers attenuated inflammatory response in the blood and brain and the activation of the lateral habenula (LHb)-ventral tegmental area (VTA) neural circuitry, which has been shown to be important for POCD. Wound infiltration with bupivacaine attenuated the activation of LHb-VTA. CONCLUSION: These results suggest that living with familiar observers attenuates POCD and neuroinflammation, possibly via inhibiting the activation of the LHb-VTA neural circuitry.

Gas Dispersion Coefficient Test System and Dimensionless Inversion Method for Porous Media.

Due to the complex porous media structure of the longwall gob area, it has been difficult to determine the gas dispersion coefficient of oxygen when studying spontaneous coal combustion in the gob area. In this work, we first designed an experimental device for testing the gas diffusion coefficient of porous media. Then, the distribution law of gas concentration in porous media under different particle size conditions was obtained by experiments. Subsequently, we established a dimensionless mathematical model of gas dispersion in porous media and developed a corresponding numerical simulator based on the finite volume method (FVM). The influence of the dimensionless gas dispersion coefficient on the gas concentration distribution was analyzed, and then a dimensionless inversion method of the gas dispersion coefficient was summarized and put forward. Finally, we obtained the values of the gas dispersion coefficient in the experimental device under different particle size conditions by inversion and discussed its effect on the gas dispersion behavior in porous media. The results show that (1) the distribution of gas concentration obtained from the experimental test and numerical simulation is consistent, which verifies the reliability of our work; (2) the dimensionless gas concentration is the highest near the injection point and gradually decreases along the depth and both sides of the test container; (3) with the increase of the dimensionless gas dispersion coefficient, the distance required for uniform gas mixing in the test container is gradually shortened and the gas dispersion coverage is wider; and (4) the larger pore space facilitates the dispersion behavior of the gas, and the gas dispersion coefficient shows a parabolic trend with the increase of porous medium particle size.

An empirical analysis of the factors driving customers' purchase intention of green smart home products.

With the improvement of consumers' environmental awareness and the popularity of the Internet of Things, green smart home products (GSHPs) are becoming the dominant trend of future home life. This shift not only makes tedious home life easier and more convenient but also helps families save energy and reduce carbon emissions. However, given the impact of the current technological level, the proportion of users who actually purchase GSHPs remains small. Thus, seeking ways to promote the consumption of GSHPs has become an urgent issue. Hence, this study seeks to fill the gap in the existing research on green consumption behavior and obtain a full understanding of the factors influencing the purchase intention of GSHPs. To do so, this work uses task-technology fit theory and considers the actual situation of green smart home consumption to add social-technology fit into the original theoretical basis. In particular, this research focuses on middle- and high-end Chinese consumers who have experience in purchasing GSHPs. Moreover, it aims for an in-depth exploration of the formation mechanism of Chinese consumers' purchase intention for GSHPs through structural equation modeling. Using survey data collected from 331 green smart home product users in China, the study empirically examines the relationships among autonomy, environmental agility, sense of belonging, and self-actualization, and both task-technology fit and social-technology fit, which are expected to shape the purchase intention of GSHP users. The empirical results provide broad support for our hypotheses. The results of this study offer important contributions to the increasing research on GSHPs consumption and shed light on the importance of both technology characteristics and the needs of users in achieving both task-technology fit and social-technology fit and, ultimately enhancing the users' intention to purchase GSHPs.

CD146 promotes malignant progression of breast phyllodes tumor through suppressing DCBLD2 degradation and activating the AKT pathway.

BACKGROUND: As a rapid-progressing tumor, breast malignant phyllodes tumors (PTs) are challenged by the lack of effective therapeutic strategies and suitable prognostic markers. This study aimed to clarify the role and mechanism of CD146 on promoting PTs malignant progression, and to identify a novel prognosis marker and treatment target of breast malignant PTs. METHODS: The expression and prognostic significance of CD146 in PTs was detected through single-cell RNA-sequencing (scRNA-seq), immunostaining, real-time PCR and other methodologies. Functional experiments including proliferation assay, colony formation assay, transwell assay, and collagen contraction assay were conducted to validate the role of CD146 in malignant progression of PTs. The efficacy of anti-CD146 monoclonal antibody AA98 against malignant PTs was corroborated by a malignant PT organoid model and a PT patient-derived xenograft (PDX) model. Transcriptome sequencing, proteomic analysis, co-immunoprecipitation, and pull-down assay was employed to identify the modulating pathway and additional molecular mechanism. RESULTS: In this study, the scRNA-seq analysis of PTs disclosed a CD146-positive characteristic in the α-SMA+ fibroblast subset. Furthermore, a progressive elevation in the level of CD146 was observed with the malignant progression of PTs. More importantly, CD146 was found to serve as an independent predictor for recurrence in PT patients. Furthermore, CD146 was found to augment the viability and invasion of PTs. Mechanistically, CD146 acted as a protective "shield" to prevent the degradation of Discoidin, CUB, and LCCL domain-containing protein 2 (DCBLD2), thereby activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and enhancing malignant behaviors of PT cells. In the malignant PT organoid and PDX model, a significant suppression of malignant PT growth was observed after the application of AA98. CONCLUSIONS: These findings suggested that CD146 served as an efficacious marker for predicting PT malignant progression and showed promise as a prognosis marker and treatment target of breast malignant PTs. The study further unveiled the essential role of the CD146-DCBLD2/PI3K/AKT axis in the malignant progression of PTs.

Numerical simulation and investigation of methane gas distribution and extraction in goaf with U-type ventilation of working face.

The accumulated methane in goaf during coal mining may leak into the working face under the airflow influence, which is possibly causing disasters such as methane gas excessive at the working face and seriously threatening the mine safety. This paper first established a three-dimensional numerical model of the mining area under U-shaped ventilation, introducing the gas state equation, continuity equation, momentum equation, porosity evolution equation, and permeability evolution equation to simulate the airflow field and gas concentration field in the mining area under the natural state. The reliability of the numerical simulations is then verified by the measured air volumes at the working face. The areas in the mining area where gas is likely to accumulate are also delineated. Subsequently, the gas concentration field in goaf under the gas extraction state was theoretically simulated for different locations of large-diameter borehole. The maximum gas concentration in goaf and the gas concentration trend in the upper corner were analyzed in detail, and the critical borehole location (17.8 m from the working face) was determined as the optimum location for gas extraction from the upper corner. Finally, a gas extraction test was carried out on-site to evaluate the application effect. The results show that the measured airflow rate has a small error with the simulated results. The gas concentration in the area without gas extraction is high, with the gas concentration in the upper corner being over 1.2%, which is greater than the critical value of 0.5%. The maximum reduction in gas concentration was 43.9%, effectively reducing the gas concentration in the extraction area after employing a large borehole to extract methane gas. The gas concentration in the upper corner and the distance of the borehole from the working face are expressed as a positive exponential function. The field engineering results show that the implementation of the large borehole at a distance of less than 17.8 m from the working face can control the gas in the upper corner to less than 0.5%, effectively reducing the risk of gas in the upper corner. The numerical simulation work in this paper can provide some basic support for the design of an on-site borehole to extract gas from the mining void and reduce the gas hazard in coal mines.

Microglial IL-1RA ameliorates brain injury after ischemic stroke by inhibiting astrocytic CXCL1-mediated neutrophil recruitment and microvessel occlusion.

Acute ischemic stroke (AIS), one of the leading causes of mortality worldwide, is characterized by a rapid inflammatory cascade resulting in exacerbation of ischemic brain injury. Microglia are the first immune responders. However, the role of postischemic microglial activity in ischemic brain injury remains far from being fully understood. Here, using the transgenic mouse line CX3 CR1creER :R26iDTR to genetically ablate microglia, we showed that microglial deletion exaggerated ischemic brain injury. Associated with this worse outcome, there were increased neutrophil recruitment, microvessel blockade and blood flow stagnation in the acute phase, accompanied by transcriptional upregulation of chemokine (C-X-C motif) ligand 1 (CXCL1). Our study showed that microglial interleukin-1 receptor antagonist (IL-1RA) suppressed astrocytic CXCL1 expression induced by oxygen and glucose deprivation and inhibited neutrophil migration. Furthermore, neutralizing antibody therapy against CXCL1 or the administration of recombinant IL-1RA protein reduced brain infarct volume and improved motor coordination performance of mice after ischemic stroke. Our study suggests that microglia protect against acute ischemic brain injury by secreting IL-1RA to inhibit astrocytic CXCL1 expression, which reduces neutrophil recruitment and neutrophil-derived microvessel occlusion.

Concurrent silencing of TBCE and drug delivery to overcome platinum-based resistance in liver cancer.

Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.

Bioactive lipid-nanoparticles with inherent self-therapeutic and anti-angiogenic properties for cancer therapy.

Angiogenesis inhibition has become a promising therapeutical strategy for cancer treatment. Current clinical anti-angiogenesis treatment includes antibodies against vascular endothelial growth factor (VEGF) or VEGF receptor, fusion proteins with high affinity to VEGF receptor, and tyrosine kinase inhibitors of VEGF receptor. However, current treatments are prone to systemic toxicity or acquiring drug resistance. A natural bioactive lipid 1,2-dipalmitoyl-sn­glycero-3-phosphate (dipalmitoyl phosphatidic acid, DPPA) was reported to exhibit anti-angiogenic and anti-tumoral activity. However, the hydrophobic property of DPPA largely restricted its clinical use, while systemic infusion of free DPPA could result in undesirable side effects. Herein, we successfully developed DPPA-based lipid-nanoparticles (DPPA-LNPs) which turns the "therapeutic payload into nanocarrier". This strategy could improve on DPPA's hydrophiliciy, thereby facilitating its systemic administration. . DPPA-LNPs not only retained the therapeutic anti-angiogenic and anti-tumoral bioactivity of parental DPPA, but also greatly improved its tumor targeting ability via enhanced permeability and retention (EPR) effect. This strategy not only eliminates the limitation of drug encapsulation rate, toxicity of the delivery vehicle; but also enhances DPPA bioacvtity in vitro and in vivo. Systemic administration of DPPA-LNPs significantly suppressed the blood vessel formation and tumor growth of triple negative breast cancer and liver cancer growth on both xenograft tumor models. STATEMENT OF SIGNIFICANCE: This is the first-in-kind self-therapeutic inherent lipid to be made into a nanocarrier, with inherent anti-angiogenic and anti-tumor properties. DPPA nanocarrier is fully natural, fully compatible with minimal systemic toxicity. DPPA nanocarrier can accumulate at high concentration at tumor via EPR effect, exerting both anti-angiogenic and anti-tumor effects in vivo. DPPA nanocarrier could be used to encapsulate biologics or small molecules for synergistic anti-cancer therapy.

Fully Natural Lecithin Encapsulated Nano-Resveratrol for Anti-Cancer Therapy.

Introduction: Chemotherapeutics are known to have undesirable side effects (i.e. nausea, weight loss, hair loss, weakened immune system, etc.) due to the non-specificity of the drugs. Encapsulation of these chemotherapeutics inside nanoparticles significantly improves the bioavailability and half-life of drugs, while increasing their tumor penetration and localization. However, most, if not all, nanoparticles in clinics or research are synthetic, with no long-term studies on the effect of these nanoparticles in vivo. Herein, we developed a synergistic resveratrol nanoparticle system by using lecithin encapsulation. Lecithin, being a fully natural phospholipid derived from soybean, possesses inherent anti-tumor activity. Methods: Lec(RSV) was successfully prepared using the nanoprecipitation method, and characterized by particle size and zeta potential analysis, and transmission electron microscopy (TEM). The in vitro cellular uptake and cytotoxic effects of Lec(RSV) were investigated in human breast cancer cell line BT474. Finally, the in vivo tumoral uptake of Lec(RSV) was carried out in the BT474 orthotopic model. Results: Lec(RSV) showed a uniform distribution of ~120 nm, with prolonged stability. Lec(RSV) showed high cellular uptake and anti-cancer properties in vitro. Time-dependent uptake in the BT474 xenograft model indicated an increased tumoral uptake and apoptosis rate at 4 hours after tail vein injection of Lec(RSV). Conclusion: Taken together, we successfully developed a fully natural Lec(RSV) that possesses potent anti-cancer activity in vitro, with good tumoral uptake in vivo. We hypothesize that Lec(RSV) could be a safe anti-cancer therapeutic that could be easily translated into clinical application.

Dexmedetomidine Ameliorates Postoperative Cognitive Dysfunction in Aged Mice.

Neuroinflammation and oxidative stress coexist and interact in the progression of postoperative cognitive dysfunction (POCD) and other neurodegenerative disease. Mounting studies reveal that Dexmedetomidine (Dex) possesses anti-inflammatory and antioxidant properties. Nevertheless, whether Dex exerts neuroprotective effect on the cognitive sequelae of oxidative stress and inflammatory process remains unclear. A mouse model of abdominal exploratory laparotomy-induced cognitive dysfunction was employed to explore the underlying mechanism of neuroprotective effects exerted by Dex in POCD. Aged mice were treated with Dex (20 µg/kg) 20 min prior to surgery. Open field test (OFT) and Morris water maze (MWM) were employed to examine the cognitive function on postoperative day 3 (POD 3) or POD 7. In the present study, mice underwent surgery exhibited cognitive impairment without altering spontaneous locomotor activity, while the surgery-induced cognitive impairment could be alleviated by Dex pretreatment. Dex inhibited surgery-induced pro-inflammatory cytokines accumulation and microglial activation in the hippocampi of mice. Furthermore, Dex decreased MDA levels, enhanced SOD activity, modulated CDK5 activity and increased BDNF expression in the hippocampus. In addition, Dex remarkably reduced the surgery-induced increased ratio of Bax/Bcl-2 and apoptotic neurons in the hippocampi of aged mice. Collectively, our study provides evidence that Dex may exert neuroprotective effects against surgery-induced cognitive impairment through mechanisms involving its anti-inflammatory and antioxidant properties, as well as the suppression on the mitochondrial permeability transition pore and apoptosis-related pathway.

Galectin-1 ameliorates perioperative neurocognitive disorders in aged mice.

INTRODUCTION: The incidence of perioperative neurocognitive disorders (PND) is higher in the elderly patients undergoing surgery. Microglia activation-mediated neuroinflammation is one of the hallmarks of PND. Galectin-1 has been identified as a pivotal modulator in the central nervous system (CNS), while the role of galectin-1 in PND induced by microglia-mediated neuroinflammation is still undetermined. METHODS: An exploratory laparotomy model anesthetized with isoflurane was employed to investigate the role of galectin-1 on PND in aged mice. Open field test and Morris water maze were used to test the cognitive function 3- or 7-days post-surgery. The activation of microglia in the hippocampus of aged mice was tested by immunohistochemistry. Western blot, enzyme-linked immunosorbent assay (ELISA), and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to elucidate the underlying mechanisms. RESULTS: Galectin-1 attenuated the cognitive dysfunction induced by surgery in aged mice and inhibited microglial activity. Moreover, galectin-1 decreased the expression level of inflammatory proteins (interleukin-1ß, interleukin-6, and tumor necrosis factor-α), and prevented neuronal loss in the hippocampus. Galectin-1 inhibited the inflammation of BV2 microglial cells induced by lipopolysaccharide via decreasing the translocation of NF-κB p65 and c-Jun, while this kind of inhibition was rescued when overexpressing IRAK1. CONCLUSION: Our findings provide evidence that galectin-1 may inhibit IRAK1 expression, thus suppressing inflammatory response, inhibiting neuroinflammation, and improving ensuing cognitive dysfunction. Collectively, these findings unveil that galectin-1 may elicit protective effects on surgery-induced neuroinflammation and neurocognitive disorders.

BDNF Participates in Chronic Constriction Injury-Induced Neuropathic Pain via Transcriptionally Activating P2X7 in Primary Sensory Neurons.

Neuropathic pain, resulting from the pathological changes of the somatosensory nervous system, remains a severe public health problem worldwide. The effect of treatment targeting neuropathic pain is very limited, as the underlying mechanism of neuropathic pain is largely unknown. In this study, we demonstrated that the expression level of brain-derived neurotrophic factor (BDNF) was remarkably and time-dependently increased in dorsal root ganglion (DRG) neurons. DRG microinjection of BDNF siRNA in DRG ameliorated chronic constriction injury (CCI) induced mechanical, thermal, and cold nociceptive hypersensitivities. Overexpressing BDNF through microinjection of the AAV5-BDNF in DRG caused enhanced responses to basal mechanical, thermal, and cold stimuli in mice exposed to CCI. Mechanically, the P2X7 promoter activity was enhanced by CCI-induced increase of DRG BDNF protein and was involved in the CCI-induced upregulation of DRG P2X7 protein. The overexpression of BDNF also increased P2X7 expression in DRG neurons, which was validated in in vivo and in vitro experiments. BDNF may exert crucial effect via transcriptionally activating the P2X7 gene in primary sensory neurons, since P2X7 acts as a role of endogenous agitator in neuropathic pain and BDNF largely co-expresses with P2X7 in DRG neurons. Therefore, our data provide evidence that BDNF may be a promising therapeutic target for neuropathic pain.

Gut Microbiome Features of Chinese Patients Newly Diagnosed with Alzheimer's Disease or Mild Cognitive Impairment.

BACKGROUND: Patients with Alzheimer's disease (AD) have gut microbiome alterations compared with healthy controls. However, previous studies often assess AD patients who have been on medications or other interventions for the disease. Also, simultaneous determination of gut microbiome in patients with mild cognitive impairment (MCI) or AD in a study is rare. OBJECTIVE: To determine whether there was a gut microbiome alteration in patients newly diagnosed with AD or MCI and whether the degree of gut microbiome alteration was more severe in patients with AD than patients with MCI. METHODS: Fecal samples of 18 patients with AD, 20 patients with MCI, and 18 age-matched healthy controls were collected in the morning for 16S ribosomal RNA sequencing. No patient had medications or interventions for AD or MCI before the samples were collected. RESULTS: Although there was no difference in the microbial α-diversity among the three groups, patients with AD or MCI had increased ß-diversity compared with healthy controls. Patients with AD had decreased Bacteroides, Lachnospira, and Ruminiclostridium_9 and increased Prevotella at the genus level compared with healthy controls. The changing direction of these genera in patients with MCI was the same as patients with AD. However, Lachnospira was the only genus whose abundance in patients with MCI was statistically significantly lower than healthy controls. Bacteroides, Lachnospira, and Ruminiclostridium_9 were positively associated with better cognitive functions whereas Prevotella was on the contrary when subjects of all three groups were considered. The negative correlation of Prevotella with cognitive functions remained among patients with MCI. CONCLUSION: Patients newly diagnosed with AD or MCI have gut dysbiosis that includes the decrease of potentially protective microbiome, such as Bacteroides, and the increase of microbiome that can promote inflammation, such as Prevotella. Our results support a novel idea that the degree of gut dysbiosis is worsened with the disease stage from MCI to AD.

Transforming Tea Catechins into Potent Anticancer Compound: Analysis of Three Boronated-PEG Delivery System.

Chemotherapy has led to many undesirable side effects, as these are toxic drugs that are unable to differentiate between cancer and normal cells. Polyphenols (tea catechins) are an ideal option as alternative chemotherapeutics owing to their inherent anticancer properties, antioxidant properties and being naturally occurring compounds, are deemed safe for consumption. However, without proper administration, the bioavailability of these compounds is low and inefficient. Therefore, proper delivery of these phenolic compounds is vital for cancer therapy. Herein, we analyzed three potential solutions to creating nanoparticle drugs using naturally occurring phenolic compounds (piceatannol (PIC), epigallocatechin gallate hydrophilic (EGCG) and l-epicatechin (EPI)). By using a simple pi-pi stacking mechanism, we utilized boronated PEG (PEG-Br) as an anchor to efficiently load EPI, PIC and EGCG, respectively, to produce three effective phenolic compound-based nanoparticles, which could be delivered safely in systemic circulation, yet detach from its cargo intracellularly to exert its anticancer effect for effective cancer therapy.

Sevoflurane increases intracellular calcium to induce mitochondrial injury and neuroapoptosis.

Sevoflurane is commonly used in clinical anesthesia. However, some reports indicated that Sevoflurane could induce mitochondrial injury and neuroapoptosis. Although the mechanism remains unclear, evidence points to the increase of intracellular calcium after administration of Sevoflurane. Herein, we sought whether the increment of intracellular Ca2+ caused by Sevoflurane administration could induce mitochondrial injury and apoptosis in primary neurons of the hippocampus. Fluo-4-acetoxymethyl ester Ca2+ probe was used for measuring intracellular Ca2+ concentrations. LDH assay, CCK-8 assay, and Western blotting were performed to confirm Sevoflurane-induced neuroapoptosis. ROS, mPTP, and ATP production were assayed to reveal mitochondrial injury. Our results indicated that Sevoflurane increased intracellular Ca2+ and neuronal death. Sevoflurane also elevated ROS and the opening of mPTP, and decreased ATP production in neurons. The expression of cytochrome c, cleaved caspase-9, cleaved caspase-3, and the ratio of Bax/Bcl-2 were also increased. By using calcium channel blocker Nimodipine, the increase of intracellular Ca2+ was attenuated, and the death rate of neurons, the ROS and opening of mPTP, decreased ATP production, the expressions of cytochrome c, cleaved caspase-9, cleaved caspase-3 and the ratio of Bax/Bcl-2 were alleviated. Our study suggested that Sevoflurane could increase intracellular Ca2+ to induce mitochondrial injury and mitochondria-mediated neuroapoptosis in neurons.

Spatial distribution, pollution, and health risk assessment of heavy metal in agricultural surface soil for the Guangzhou-Foshan urban zone, South China.

During the past decades, heavy metal pollution in agricultural soil and its impact on human health have been becoming one of the most important global environmental problems. In this research, heavy metal (Cu, Pb, Zn, Cr, Cd, Ni, As, Hg) concentrations were measured for four hundred and two soil samples collected from agricultural area within the Guangzhou-Foshan urban zone. Soil heavy metal pollution was evaluated used geoaccumulation index and potential ecological risk index. The dose response model proposed by the USEPA was used to estimate the potential health risk caused by heavy metals in agricultural soil. The results showed that: 1) Cd and Hg were the main heavy metal pollutants in agricultural soil of the study area. 89.1% and 93.3% of total soil samples suffered medium to heavy potential ecological risk caused by Cd and Hg, respectively. 2) The THI and TCR were respectively greater than 1.0 and 1.0×10-4, indicating that heavy metals in agricultural soil were likely to constitute non-carcinogenic and carcinogenic risks, both of which were mainly brought by product consumption, to the public in the study area. The non-carcinogenic risks were mainly caused by Cr and As, while the carcinogenic risks were mainly from Cr, Cd, and As.

Light grazing facilitates carbon accumulation in subsoil in Chinese grasslands: A meta-analysis.

Grazing by livestock greatly affects the soil carbon (C) cycle in grassland ecosystems. However, the effects of grazing at different intensities and durations on the dynamics of soil C in its subsoil layers are not clearly understood. Here, we compiled data from 78 sites (in total 122 published studies) to examine the effects of varying grazing intensities and durations on soil C content at different depths for grasslands in China. Our meta-analysis revealed that grazing led to an overall decrease in soil C content and productivity of above-ground vegetation (e.g., above-ground biomass and litter) but an increase in below-ground biomass. Specifically, the effects of grazing on soil C content became less negative or even positive with increasing soil depths. An increase of soil C content was consequently found under light grazing (LG), although soil C content still decreased under moderate and heavy grazing. The increase in soil C content under LG could be largely attributed to the increase of soil C content in subsoil layers (>20 cm), despite that soil C content in surface soil layer (0-20 cm) decreased. Moreover, the magnitude of increase in soil C content under LG in subsoil layers increased with grazing duration. A possible reason of the increase in soil C content in the subsoil layers was due to the increases in below-ground biomass. Our study highlights that LG may modify the allocation of C input and promote its accumulation in subsoil layers, thus offsetting the negative impact of grazing on surface soil C content, a finding that has significant implications for C sequestration in grasslands.

Using sternal angle as anatomic landmark for right internal jugular vein catheterization in pediatrics.

BACKGROUND: Many formulas based on the patient's height, weight and/or age exist to determine central venous catheter (CVC) depth in children. However, this information is unavailable in some emergency conditions. Therefore, direct methods should be developed to guide catheter position in children. METHODS: Eighty patients aged 1-10 y were enrolled from July 2015 to August 2016 and seventy-five were completed; fifty were male, and twenty-five were female. The exclusion criteria were inability to identify the sternal angle or failure to use the right internal jugular vein approach. The catheter was inserted using the right internal jugular vein approach, the distance from the skin puncture point to the midpoint of the sternal angle plane was measured, and the catheter tip was positioned to this distance minus 1 cm. Chest radiography were performed for those children after catheter insertion. The relative position between the catheter tip and carina was confirmed and the longitudinal distance from the catheter tip to the carina was calculated on radiographic images, and related complications were recorded. RESULTS: All catheter tips were above the carina, and the average distance from the catheter tip to the carina was 9.8 mm. No patients experienced serious complications. CONCLUSION: The sternal angle is a useful and reliable anatomic landmark for guiding CVC position in children. Using this landmark, the catheter can be quickly and conveniently placed at a safety position in right internal jugular vein, especially in some emergency conditions.

Morphine Promotes the Angiogenesis of Postoperative Recurrent Tumors and Metastasis of Dormant Breast Cancer Cells.

BACKGROUND: Surgery plays a significant role in the comprehensive treatment of breast cancer, and opioids are often the first-choice analgesics in the perioperative period. However, recent studies showed that opioids may enhance the angiogenesis of breast cancer and the recurrence and metastasis of tumor cells. OBJECTIVES: We aim to investigate the influence of opioids on recurrence and metastasis of breast cancer in nude mice. METHODS: Forty female nude mice with breast tumor were randomly divided into 4 groups (n = 10). They were treated with (i) normal saline (10 mL/kg), (ii) morphine (10 mg/kg), (iii) morphine plus naloxone (10 + 4 mg/kg), and (iv) naloxone (4 mg/kg) for 2 weeks. Four groups of MDA-MB-231 cells were administered (i) Dulbecco's Modified Eagle's Medium, (ii) morphine (10 µmol/mL), (iii) morphine plus naloxone (10 + 10 µmol/mL), and (iv) naloxone (10 µmol/mL). The influence of morphine in each treated group was evaluated by immunocytochemistry and Western blotting. RESULTS: Mice in the morphine group had higher rates of Ki67-positive cells, lower rates of apoptotic index, and a significant increase in the microvessels density of the tumor as evidenced by CD31 staining (p < 0.05). Furthermore, the MDA-MB-231 cells in the morphine group showed an increase in p-Akt, c-Myc, and thrombosponin-1 expression. CONCLUSION: In the current study, we found that morphine promotes the angiogenesis of the recurrent postoperative tumors of nude mice with breast cancer and the proliferation of tumor cells and such promotion may be related to the PI3K-c-Myc signaling pathway.