TRPV1 Dysfunction Impairs Gastric Nitrergic Neuromuscular Relaxation in High-Fat Diet-Induced Diabetic Gastroparesis Mice.

Diabetic gastroparesis (DGP) is characterized by delayed gastric emptying of solid food. Nitrergic neuron-mediated fundus relaxation and intragastric peristalsis are pivotal for gastric emptying and are impaired in DGP. Transient receptor potential vanilloid 1 (TRPV1) ion channels are expressed in gastrointestinal vagal afferent nerves and have a potential role in relevant gastrointestinal disorders. In this study, mice with high-fat diet (HFD)-induced type 2 diabetes mellitus (T2DM), associated with gastroparesis, were used to determine the role of TRPV1 in DGP. After feeding with HFD, mice exhibited obesity, hyperglycemia, insulin resistance, and delayed gastric emptying. Cholinergic- and nitrergic neuron-mediated neuromuscular contractions and relaxation were impaired. The antral tone of the DGP mice was attenuated. Interestingly, activating or suppressing TRPV1 facilitated or inhibited gastric fundus relaxation in normal mice. These effects were neutralized by using a nitric oxide synthase (NOS) inhibitor. Activation or suppression of TRPV1 also increased or reduced NO release. TRPV1 was specifically localized with neuronal NOS in the gastric fundus. These data suggest that TRPV1 activation facilitates gastric fundus relaxation by regulating neuronal NOS and promoting NO release. However, these effects and mechanisms disappeared in mice with DGP induced by HFD diet. TRPV1 expression was only marginally decreased in the fundus of DGP mice. TRPV1 dysfunction may be a potential mechanism underlying the dysfunction of DGP gastric nitrergic neuromuscular relaxation.

Roflumilast, a phosphodiesterase-4 inhibitor, improves hyperoxia-induced lung injury via anti-inflammation.

Roflumilast is an inhibitor of phosphodiesterase-4 (PDE4) and can suppress the hydrolysis of cAMP in inflammatory cells, conferring anti-inflammatory effects. This study aimed to investigate the protective effects of roflumilast on hyperoxia-induced acute lung injury (HALI) in a rat model. Male Sprague-Dawley rats were randomly assigned into: control group; HALI group; 2.5 mg/kg roflumilast group; and 5 mg/kg roflumilast group. Rats were pressurized to 250 kPa with pure oxygen to induce lung injury. In the roflumilast groups, rats were orally administered with roflumilast at 2.5 or 5 mg/kg once before hyperoxia exposure and once daily for two days after exposure. Rats were sacrificed 72 hours after hyperoxia exposure. The lung tissues were collected for the detection of lung water content, inflammatory cytokines and NF-κB/p-NF-κB protein expression, and the bronchoalveolar lavage fluid was harvested for the measurement of protein concentration and lactate dehydrogenase activity. Results showed roflumilast at different doses could significantly reduce lung edema, improve lung pathology and reduce the expression of inflammatory cytokines in the lung. The protective effects seemed to be related to the dose of roflumilast. Our study indicates roflumilast has the potential as a medication for the treatment of HALI.

Sensitive detection of polycyclic aromatic hydrocarbons with gold colloid coupled chloride ion SERS sensor.

A simple surface-enhanced Raman spectroscopy (SERS) sensor based on an undecorated gold-colloid substrate was developed for the rapid and effective detection of polycyclic aromatic hydrocarbons (PAH). The SERS enhancement of the bare Au nanoparticles for PAH was achieved by adjusting chemical reduction conditions and Cl- content. The strongest SERS response of this system was achieved with 2.0 mL of trisodium citrate (1%) and 80 µL of NaCl (1 M). With this simple SERS sensor, qualitative and quantitative determination of trace-level naphthalene (NaP), phenanthrene (PHE) and pyrene (PYR) were achieved using a portable Raman spectrometer at detection limits of 1.38 µg L-1, 0.23 µg L-1, and 0.45 µg L-1, respectively. Plots of SERS intensity vs. PAH concentrations were linear, with correlation coefficients (R2) ranging from 0.8729 to 0.9994. More importantly, the SERS sensor was able to accurately identify each PAH in complex mixtures. This SERS technique shows great promise for the rapid and direct detection of aromatic hydrocarbons organic pollutants in field.

Time-dependent functional, morphological, and molecular changes in diabetic bladder dysfunction in streptozotocin-induced diabetic mice.

AIM: Diabetic bladder dysfunction (DBD) is one of the most common and bothersome complications of diabetes mellitus (DM). This study aimed to investigate the functional, structural, and molecular changes of the bladder at 0, 3, 6, 9, and 12 weeks after DM induction by streptozotocin (STZ) in male C57BL/6 mice. METHODS: Male C57BL/6J mice were injected with STZ (130 mg/kg). Then, diabetic general characteristics, cystometry test, histomorphometry, and contractile responses to α, ß-methylene ATP, KCl, electrical-field stimulation, carbachol were performed at 0, 3, 6, 9, and 12 weeks after induction. Finally, protein and messenger RNA (mRNA) expressions of myosin Va and SLC17A9 were quantified. RESULTS: DM mice exhibited lower body weight, voiding efficiency and higher water intake, urine production, fasting blood glucose, oral glucose tolerance test, bladder wall thickness, maximum bladder capacity, residual volume, bladder compliance. In particular, nonvoiding contractions has increased more than five times at 6 weeks. And the amplitudes of spontaneous activity, contractile responses to all stimulus was about two times higher at 6 weeks but cut almost in half at 12 weeks. The protein and mRNA expressions of myosin Va and SLC17A9 were about two times higher at 6 weeks, but myosin Va was reverted nearly 40% while SLC17A9 is still higher at 12 weeks. CONCLUSIONS: DBD transitioned from a compensated state to a decompensated state in STZ-induced DM mice at 9 to 12 weeks after DM induction. Our molecular data suggest that the transition may be closely related to the alterations of myosin Va and SLC17A9 expression levels in the bladder with time.

Effects of Radix Linderae extracts on a mouse model of diabetic bladder dysfunction in later decompensated phase.

BACKGROUND: This study aimed to elucidate the effects and mechanisms of Radix Linderae (RL) extracts on a mouse model of diabetic bladder dysfunction (DBD), especially on later decompensated phase. METHODS: Male C57BL/6J mice were intraperitoneally injected with streptozotocin (STZ) after 4 weeks of high-fat diet (HFD) feeding. DBD mouse models (later decompensated phase) were developed by 12-weeks persistent hyperglycemia and then treated with RL extracts for 4 weeks. During administration, the fasting blood glucose (FBG) test was performed once a week. Four weeks later, oral glucose tolerance test (OGTT), voided stain on paper (VSOP), and urodynamic alteration were explored. We also performed haematoxylin and eosin (H&E) and Masson's trichrome staining to observe the histology of the bladder. Then, the contractile responses to α, ß-methylene ATP, capsaicin (CAP), KCl and carbachol were measured. Moreover, qPCR assay was performed to analyse the bladder gene expression levels of M3 receptors and TRPV1. RESULTS: The diabetic mice exhibited higher FBG, OGTT and urine production, and no substantial alteration was observed after RL treatment. Urodynamic test showed the maximum bladder capacity (MBC), residual volume (RV) and bladder compliance (BC), as well as the decrement of voided efficiency (VE) and micturition volume (MV), remarkably increased in the DBD mice. Furthermore, RL treatment significant improved urodynamic urination, with lower MBC, RV, and, BC, as well as higher VE and MV, as compared with the model groups. The wall thickness of the bladder and the ratio of smooth muscle/collagen remarkably increased, and RL could effectively attenuate the pathological change. The response of bladder strips to the stimulus was also reduced in the DBD mice, and RL treatment markedly increased the contraction. Furthermore, the gene expression levels of M3 receptors and TRPV1 were down-regulated in the bladders of the diabetic mice, whereas RL treatment retrieved those gene expression levels. CONCLUSIONS: RL extracts can improve the bladder voiding functions of the DBD model mice in later decompensated phase, and underlying mechanisms was associated with mediating the gene expression of M3 receptors and TRPV1 in the bladder instead of improving blood sugar levels.

Removal of polycyclic aromatic hydrocarbons from different soil fractions by persulfate oxidation.

Removal of polycyclic aromatic hydrocarbons (PAHs) from different soil fractions of contaminated soil was investigated by using activated persulfate oxidation remediation in our research. The results showed that the light fraction, which accounted for only 10% of the soil, contained 30% of the PAHs at a concentration of 4352 mg/kg. The heavy fraction contained more high-molecular-weight PAHs, and the total PAH concentration was 625 mg/kg. After being oxidized, the removal rate of PAHs was 39% in the light fraction and nearly 90% in the heavy fraction. Among the different fractions of the heavy fraction, humic acid contained the highest concentration of PAHs, and consequently, the highest removal efficiency of PAHs was also in humic acid. Compared with the light fraction, the heavy fraction has more aromatic compounds and those compounds were broken down during the oxidation process, which may be the removal mechanism involved in the oxidation of high-ring PAHs. Similarly, the enhancement of C=C bonds after oxidation can also explain the poor removal of high-ring PAHs in the light fraction. These results imply that different fractions of soil vary in composition and structure, leading to differences in the distribution and oxidation efficiencies of PAHs.

Key Anti-Fibrosis Associated Long Noncoding RNAs Identified in Human Hepatic Stellate Cell via Transcriptome Sequencing Analysis.

Hepatic fibrosis is the main pathological basis for chronic cirrhosis, and activated hepatic stellate cells (HSCs) are the primary cells involved in liver fibrosis. Our study analyzed anti-fibrosis long noncoding RNAs (lncRNAs) in activated human HSCs (hHSCs). We performed RNA sequencing (RNA-seq) and bioinformatics analysis to determine whether lncRNA expression profile changes between hHSCs activation and quiescence. Eight differentially expressed (DE) lncRNAs and three pairs of co-expression lncRNAs-mRNAs were verified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). A total of 34146 DE lncRNAs were identified in this study. Via gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, we found several DE lncRNAs regulated hHSC activation by participating in DNA bending/packaging complex, growth factor binding and the Hippo signaling pathway (p < 0.05). With lncRNA-mRNA co-expression analysis, three lncRNAs were identified to be associated with connective tissue growth factor (CTGF), fibroblast growth factor 2 (FGF2) and netrin-4 (NTN4). The quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) results of the eight DE lncRNAs and three pairs of co-expression lncRNAs-mRNAs were consistent with the RNA-seq data and previous reports. Several lncRNAs may serve as potential targets to reverse the progression of liver fibrosis. This study provides a first insight into lncRNA expression profile changes associated with activated human HSCs.

Effect of the serum of rats treated with Suo Quan pill on embryonic stem cells.

Suo Quan pill(SQP), a well-known and classical traditional Chinese medicine compound, consists of three traditional Chinese medicine: Alpinia oxyphylla Miq., Lindera aggregata (Sims) Kosterm., Dioscorea opposite. Its effect was summarized as supplementing kidney-yang and shrinkaging urination. This study evaluated the effects of the serum of rats treated with Suo Quan pill on embryonic stem cells(ES cells). Cell proliferation was detected by MTT assay. Cell cycle and apoptosis of ES cells were evaluated with flow cytometry. Nanog mRNA expression was verified by fluorescence quantitative PCR and Nanog protein in ES cells was determined by Western blot. The serum of SQP-treated rats not only promoted ES cells proliferation and Nanog expression in ES cells, but also inhibited H202 stimulated cell apoptosis. Furthermore, the serum of rats containing SQP affected the cell cycle distribution of ES cells, reducing the percentage of cells in G0/G1phase and increasing the percentage of cells in G2/M phase, increasing the proliferation index of ES cells. These results illustrate that the enhanced effect of SQP on ES cells proliferation is in part due to the increased expression of Nanog in ES cells, the accelerated cell cycle period and the inhibited apoptosis of ES cells.

[Mechanism of anti-Helicobacter pylori urease activity of patchouli alcohol].

To investigate the effect of patchouli alcohol on inhibiting Helicobater pylori urease activity, and its effect on expression levels of related genes, and lay the foundation for further research on the effect of patchouli alcohol on H. pylori colonization and infection. H. pyloriwas cultured and identified by gram staining, rapid urease test (RUT) and PCR method. Then agar dilution method was used to detect the bacterial survival after 1 h intervention by different concentrations of patchouli alcoholin the acidic (pH 5.3) and neutral (pH 7.0) conditions; berthelot method was used to detect urease activity and RT-qPCR method was used to detect the expression changes of ureA, ureB, ureE, ureH, ureI, and nixA related urease genes. The results showed that the survival rate of H. pyloriwas not significantly changed but the urease activity was obviously decreased after intervention by different concentrations of patchouli alcohol; meanwhile, the expression levels of ureA, ureB, ureE, ureH, ureI, and nixA were decreased to different degrees. Therefore, patchouli alcohol could inhibit H. pylori urease activity in both acidic and neutral conditions, and the mechanism may be related to down-regulation of urease gene expression.

Effect of SQW on the bladder function of mice lacking TRPV1.

BACKGROUND: Suo Quan Wan (SQW) is an effective traditional Chinese prescription on treated lower urinary tract symptoms (LUTS), and has been proved have modulation effect on the expression of transient receptor potential vanilloid 1 (TRPV1) in accordance with the recovery of bladder function of overactive bladder rat. This study further investigated the mechanism of SQW modulated TRPV1 signaling and bladder function using TRPV1 knockout (KO) mice. METHODS: Study was conducted using wild type and TRPV1 KO mice. The KO animals were grouped into KO group and SQW treated group. We applied in vivo cystometrogram recording techniques to analyze voiding control of the urinary bladder, as well as in vitro organ bath to study bladder distension response to various compounds, which subsequently elicited normal smooth muscle excitation. Real-time polymerase chain reaction and western blot analysis were performed to quantify the expression of TRPV1 and P2X3 in the bladder. ATP released from bladder strips was measured using the luciferin-luciferase ATP bioluminescence assay kit. RESULTS: KO preparation inhibited decrease micturition times, while micturition interval and volume were increased. Results of urodynamic record of the TRPV1-/- mice during NS infusion showed reduced bladder pressure and contraction which exhibited decreased response to α, ß-me ATP, KCl, and carbachol and no response to CAP. The ATP released by the TRPV1-/- mice from strips of bladder smooth muscles was significantly reduced, along with no TRPV1 expression and reduced expression level of P2X3 in the bladder. SQW could increase ATP release in some degree, while had no effect on TRPV1 and P2X3 expression. SQW could improve bladder pressure slightly, while make no significantly effects on the force response to α,ß-meATP, CAP, carbachol in gradient concentration, and KCl, as well as MBC and voiding activities. CONCLUSIONS: TRPV1 plays an important role in urinary bladder mechanosensitivity. The effective SQW is hard to play its proper role on bladder function of mice without TRPV1.

Effect of the Chinese traditional prescription Suo Quan Wan on TRPV1 expression in the bladder of rats with bladder outlet obstruction.

BACKGROUND: Suo Quan Wan (SQW) is a Chinese traditional prescription that has been used in clinical treatment of lower urinary tract symptoms for centuries. However, scientific basis of SQW efficacy and mechanism is still needed. This study investigated the effect of SQW on bladder function and transient receptor potential vanilloid 1 (TRPV1) expression in the bladder of rats with bladder outlet obstruction (BOO). The induced changes in bladder function in overactive bladder (OAB) rat model were observed following different periods of outlet obstruction to obtain an appropriate rat model. METHODS: This study was carried out in two parts. In the first part, female Sprague-Dawley rats received sham operations or partial BOO operations. Two, four, and six weeks later, the OAB model groups and control were subjected to urodynamic tests to measure differences in bladder functions. Once the appropriate rat model was obtained, the second part of the experiment was performed. The rat model was recreated and treated with SQW. Urodynamic assessment was conducted, and the bladders of the rats were then removed. Immunofluorescence staining, real-time PCR, and Western blot were performed to localize and quantify the expression of TRPV1 in the bladder. RESULTS: Results of the first part indicated that at 2 and 4 weeks, the OAB model group exhibited significant differences in urodynamic parameters, including bladder pressure, maximum voiding pressure, and maximum bladder capacity, compared with the sham group. At 4 and 6 weeks, the OAB model group exhibited significant differences in residual volume (RV) and non-voiding contraction frequency. Six-week OAB model group showed much more RV but less voiding efficiency when compared with 6-week sham group or 2-and 4-week OAB model group. Rats that underwent BOO exhibited similarities with the compensated state before four weeks and may have entered decompensated state at six weeks. Studies conducted with 4-week OAB model were appropriate. In part two of the experiment, unstable bladder in the OAB model group recovered bladder stability after SQW treatment, accompanied by improved bladder hypertrophy, as well as corrected urodynamic parameters. Expression of TRPV1 mRNA and proteins in the bladder was significantly greater in the OAB model group than that in the control group, which subsequently decreased significantly with SQW treatment in BOO-induced rats. CONCLUSIONS: SQW can modulate the expression of TRPV1 in accordance with the recovery of bladder function.

[Effects of Suoquan Wan and Shenqi Wan on Urethra Function and ß-AR Function of Detrusor in Natural Aged Rats].

OBJECTIVE: To investigate the effect of Suoquan Wan(SQW) and Jinkui Shenqi Wan(JKSQW) on urethra function and ß6-AR function of detrusor in natural aged rats. METHODS: young rats(3 months) and Aged rats(15 months) were chosen. Young rats were chosen as control, aged rats were randomly divided into three groups: model, JKSQW and SQW groups, 12 rats in each group. JKSQW and SQW were given the appropriate concentration once a day for six weeks. The effects of SQW and JKSQW on relaxation function of bladder detrusor was investigated, and their effects on bladder induced by ß3-AR agonist and ß3-AR agonist were further studied. Then, their effects on pressure of urethra were observed. RESULTS: Compared with the young group, detrusor compliance of natural aged model rats was increased, Emax and IA of agonist of ß3-AR including BRL37344 and ISO were decreased(P <0. 01), while PA2 of antagonist of ß3-AR were increased(P <0. 05). Compared with model group, SQW and JKSQW decreased the bladder compliance(P <0. 05), and increased Emax, IA and PD2 due to sensitivity of detrusor to agonist of ß3-AR and ß3-AR including BRL37344 and ISO(P <0. 05 or P < 0. 01) ,while decreased PA2 of antagonist of ß3-AR(P <0. 05). MUCP, MUP and FUL of aged rats were lower than those of normal rats. But SQW and JKSQW increased MUCP and MUP, and JKSQW increased FUL of aged rats(P <0. 05 or P <0. 01). CONCLUSION: SQW and JKSQW can remarkably adjust ß3-AR function on the detrusor and improve the closure ability of bladder detrusor of the natural aged rats.

Corrigendum: Patchouli alcohol improved diarrhea-predominant irritable bowel syndrome by regulating excitatory neurotransmission in the myenteric plexus of rats.

[This corrects the article DOI: 10.3389/fphar.2022.943119.].

Properties and inflammatory effects of various size fractions of ambient particulate matter from Beijing on A549 and J774A.1 cells.

Particulate matter (PM) is a major ambient air pollutant causing millions of premature deaths each year in China. The toxicity of PM is property and size dependent. In this study, ambient PM samples collected in Beijing were divided into five size fractions with nominal aerodynamic ranges of <0.40, 0.40-1.1, 1.1-3.3, 3.3-5.8, and 5.8-10 µm. Individual size fractions were characterized for a number of properties including particle size distribution, specific surface area, zeta potential, dithiothreitol (DTT)-based redox ability, and contents of water-soluble organic carbon (WSOC), polycyclic aromatic hydrocarbons (PAHs), selected metals, and endotoxin. Human adenocarcinomic alveolar epithelial cell line A549 and small mouse monocyte-macrophage cell line J774A.1 were tested for their relative viabilities and inflammatory effects (interleukine-8 for A549 and tumor necrosis factor-α for J774A.1) after exposure to PM of various sizes. It was found that PM specific area was positively correlated with WSOC, high molecular weight PAHs, DTT-based redox ability, negatively correlated with surface zeta potential and lithophile metals. Several trace metals from combustion sources were enriched in intermediate size fractions. For both endotoxin concentrations of the PM and PM induced inflammatory cytokine expressions by the two cell lines, there were general increasing trends as PM size increased with an exception of the finest fraction, which induced the highest inflammatory effects. It seems that the size dependence of cytokine expression was associated with a number of properties including endotoxin content, zeta potential, settling velocity, metal content, and DTT-based redox ability.

[Study on efficacy and mechanism of weiyangning pills against experimental gastric ulcer].

OBJECTIVE: To study the efficacy and mechanism of Weiyangning pills against experimental gastric ulcer. METHOD: The gastric ulcer model were established by acetic acid, water-immersion stress, aspirin induction, pyloric ligation in rats, in order to observe the effect of Weiyangning pills against experimental gastric ulcer and study its effect on the content of nitric oxide (NO) and epidermal growth factor (EGF), gastric mucosal blood flow, the content of PGE2, gastric secretion, gastric acid content and the activity of pepsin. RESULT: Weiyangning pills markedly reduced index of gastric ulcers of various types, increased the content of NO, EGF, PGE2 and gastric mucosal blood flow, inhibited gastric secretion and gastric acid content, and decreased the activity of pepsin. CONCLUSION: Weiyangning pills has a significant effect against experimental gastric ulcer, which is related to the reduction of gastric mucosa damage factors (gastric acid and pepsin) and the increase in gastric mucosa's function as a barrier and its recovery effects, such as NO, EGF, PGE2 and gastric mucosal blood flow.

Three-dimensional distribution characteristics of multiple pollutants in the soil at a steelworks mega-site based on multi-source information.

Soil pollution at steelworks mega-sites has become a severe environmental issue worldwide. However, due to the complex production processes and hydrogeology, the soil pollution distribution at steelworks is still unclear. This study scientifically cognized the distribution characteristics of polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs), and heavy metals (HMs) at a steelworks mega-site based on multi-source information. Specifically, firstly, 3D distribution and spatial autocorrelation of pollutants were obtained by interpolation model and local indicators of spatial associations (LISA), respectively. Secondly, the characteristics of horizontal distribution, vertical distribution, and spatial autocorrelations of pollutants were identified by combining multi-source information such as production processes, soil layers, and properties of pollutants. Horizontal distribution showed that soil pollution in steelworks mainly occurred in the front end of the steel process chain. Over 47% of PAHs and VOCs pollution area were distributed in coking plants and over 69% of HMs in stockyards. Vertical distribution indicated that HMs, PAHs, and VOCs were enriched in the fill, silt, and clay layers, respectively. Spatial autocorrelation of pollutants was positively correlated with their mobility. This study clarified the soil pollution characteristics at steelworks mega-sites, which can support the investigation and remediation of steelworks mega-sites.

Excitatory purinergic and cholinergic expression changed in a partial bladder outlet obstruction-induced overactive bladder rat model.

Overactive bladder (OAB) is a common, long-term symptom complex with a high prevalence in women worldwide. OAB has caused a social burden, and effective treatments are urgently needed. However, the pathogenesis of OAB has yet to be elucidated. Model rats underwent bladder outlet obstruction surgery. In the 2nd, 3rd, and 4th weeks after surgery, metabolic cages were used to detect the 12 h urine volume of rats in the sham and model groups. The urodynamic parameters bladder leak point pressure (BPLL), maximum voiding pressure (MVP), residual volume (RV), maximum bladder capacity (MBC), bladder compliance (BC), voided efficiency (VE), and non-voiding contractions (NVCs) were also detected. Moreover, the contractile responses of isolated detrusor muscles to electrical and carbachol stimulation were examined at the abovementioned time points. At the 4th week after surgery, the bladders of both groups were obtained for hematoxylin-eosin (H&E) and Masson's trichrome staining. Real-time qPCR and Western blot were performed to quantify the expression of choline acetyltransferase (ChAT) and solute carrier family 17 member 9 (SLC17A9). At week 4, compared with the sham group, the 12 h urine volume of PBOO group increased significantly. The BLPP, MVP, VE, MBC, and NVCs increased significantly, and the VE was significantly reduced in 4-week PBOO group. The contractile responses of isolated detrusor muscles to electrical and carbachol stimulation significantly increased in 4-week PBOO group. In the 4-week PBOO group, the bladder wall and the ratio of bladder muscle to collagen within the bladder smooth muscle layer wall were significantly higher than those in the sham group. ChAT and SLC17A9 mRNA and protein expression in the OAB model rats significantly increased. At 4 weeks after PBOO, the OAB model was successfully established. The gene and protein expression levels of ChAT and SLC17A9 increased in the bladder of the OAB model, suggesting that OAB may be related to increased excitatory purinergic and cholinergic expression.

Variations of microbiota in three types of typical military contaminated sites: Diversities, structures, influence factors, and co-occurrence patterns.

Contamination with energetic compounds (ECs) is common in military sites and poses a great risk to the environment and human health. However, its effects on the soil bacterial communities remain unclear. This study assessed the variations of bacterial communities, co-occurrence patterns, and their influence factors in three types of typical military-contaminated sites (artillery range, military-industrial site, and ammunition destruction site). The results showed that the most polluted sites were ammunition destruction sites, followed by military-industrial sites, whereas pollution in the artillery ranges was minimal. The average concentrations of ECs including 2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) in the study sites ranged 120-1.67 × 105, 20-7.20 × 104, and 180-2.38 × 105 µg/kg, respectively. Bacterial diversity and community structure in military-industrial and ammunition destruction sites were significantly changed, but not in artillery ranges. TNT, pH, and soil moisture are the critical factors affecting bacterial communities in contaminated military sites. Co-occurrence network analysis indicated that the pressure of ECs affected bacterial interactions and microbiota function. Our findings provide new insights into the variations in bacterial communities in EC-contaminated military sites and references for the bioremediation of ECs.

Effects of NBP on postoperative cognitive dysfunction in rats via Nrf 2/ARE pathway.

OBJECTIVE: Postoperative cognitive dysfunction (POCD) is a common postoperative disease that threatens patients' quality of life, especially elderly patients. With the popularity of anesthesia/surgery, POCD has received more attention worldwide. The objective of this research is to evaluate 3-n-Butylphthalide (NBP)'s protective effect on postoperative cognitive function in rats and its related mechanisms. METHODS: Tibial fracture models of senile rats of POCD were established and divided into blank control group, solvent group, NBP group, Nrf 2 agonist group, and Nrf 2 inhibitor group. The changes in the cognitive abilities of rats were systematically evaluated by the Morris water maze test. After hematoxylin-eosin (HE) staining of the hippocampus, the morphological and structural changes of hippocampal neurons were observed by light microscopy. The expressions of apoptosis-related proteins were analyzed by immunohistochemistry and Western blot was used to detect the expressions of Nrf 2,HO-1,Mfn1,Mfn2,Drp1 proteins. Moreover, the changes in the morphology of mitochondria were observed by transmission electron microscopy. RESULTS: Through the water maze test, we observed that the incidence of postoperative cognitive impairment in the NBP, agonist, and inhibitor groups was substantially lower as compared to the blank control group and solvent group (P < 0.05). The expressions of Nrf 2, HO-1, Mfn1, Mfn2, and Drp1 proteins in the NBP group were upregulated in comparison to the blank control group and the solvent group. The expressions of related proteins in the inhibitor group were substantially lower in comparison to the NBP group. CONCLUSIONS: NBP can affect the postoperative cognitive function of rats by activating the Nrf 2/ARE signaling pathway.

Spatial-vertical variations of energetic compounds and microbial community response in soils from an ammunition demolition site in China.

Ammunition-related activities have caused severe energetic compound (EC) contamination and pose serious risks to ecosystems. However, little is known regarding the spatial-vertical variations of ECs or their migration in soils at ammunition demolition sites. Although the toxic effect of some ECs to microorganisms have been reported through laboratory simulations, the responses of indigenous microbial communities to ammunition demolition activities are unclear. In this study, the spatial-vertical variations of ECs in 117 topsoil samples and three soil profiles from a typical ammunition demolition site in China were studied. Heavy contamination of ECs was concentrated in the top soils of the work platforms, and ECs were also detected in the surrounding area and nearby farmland. ECs showed different migration characteristics in the 0-100 cm soil layer of the different soil profiles. Demolition activities and surface runoff play critical roles in the spatial-vertical variations and migration of ECs. These findings suggest that ECs are able to migrate from the topsoil to the subsoil and from the core demolition area to further ecosystems. The work platforms exhibited lower microbial diversity and different microbiota compositions compared to the surrounding areas and farmlands. Using the random forest analysis, pH and 1,3,5-trinitrobenzene (TNB) were characterized as the most important factors affecting microbial diversity. Network analysis revealed that Desulfosporosinus was highly sensitive to ECs and may be a unique indicator of EC contamination. These findings provide key information in understanding EC migration characteristics in soils and the potential threats to indigenous soil microorganisms in ammunition demolition sites.