Superoxide dismutase 1-modified dental pulp stem cells alleviate high-altitude pulmonary edema by inhibiting oxidative stress through the Nrf2/HO-1 pathway.

High-altitude pulmonary edema (HAPE) is a deadly form of altitude sickness, and there is no effective treatment for HAPE. Dental pulp stem cells (DPSCs) are a type of mesenchymal stem cell isolated from dental pulp tissues and possess various functions, such as anti-inflammatory and anti-oxidative stress. DPSCs have been used to treat a variety of diseases, but there are no studies on treating HAPE. In this study, Sprague-Dawley rats were exposed to acute low-pressure hypoxia to establish the HAPE model, and SOD1-modified DPSCs (DPSCsHiSOD1) were administered through the tail vein. Pulmonary arterial pressure, lung water content (LWC), total lung protein content of bronchoalveolar lavage fluid (BALF) and lung homogenates, oxidative stress, and inflammatory indicators were detected to evaluate the effects of DPSCsHiSOD1 on HAPE. Rat type II alveolar epithelial cells (RLE-6TN) were used to investigate the effects and mechanism of DPSCsHiSOD1 on hypoxia injury. We found that DPSCs could treat HAPE, and the effect was better than that of dexamethasone treatment. SOD1 modification could enhance the function of DPSCs in improving the structure of lung tissue, decreasing pulmonary arterial pressure and LWC, and reducing the total lung protein content of BALF and lung homogenates, through anti-oxidative stress and anti-inflammatory effects. Furthermore, we found that DPSCsHiSOD1 could protect RLE-6TN from hypoxic injury by reducing the accumulation of reactive oxygen species (ROS) and activating the Nrf2/HO-1 pathway. Our findings confirm that SOD1 modification could enhance the anti-oxidative stress ability of DPSCs through the Nrf2/HO-1 signalling pathway. DPSCs, especially DPSCsHiSOD1, could be a potential treatment for HAPE. Schematic diagram of the antioxidant stress mechanism of DPSCs in the treatment of high-altitude pulmonary edema. DPSCs can alleviate oxidative stress by releasing superoxide dismutase 1, thereby reducing ROS production and activating the Nrf2/HO-1 signalling pathway to ameliorate lung cell injury in HAPE.

A Preliminary Discussion on the Safety of Mild Therapeutic Hypothermia in Target Vessels after Endovascular Intervention in Acute Large Vessel Occlusion Cerebral Infarction.

INTRODUCTION: The aim of this study was to discuss the safety of rapid administration of 4°C hypothermic normal saline into the occluded vessels using an intra-arterial catheter to induce mild hypothermia following endovascular thrombectomy in patients with acute large vessel occlusion cerebral infarction. METHODS: We selected 78 patients with acute large vessel occlusion cerebral infarction who underwent endovascular thrombectomy in the Department of Neurology of our hospital from January 2020 to July 2022 and achieved TICI 2b recanalization. RESULT: Twenty-five patients were administered 500 mL of 4°C hypothermic normal saline in the occluded vessels at a rate of 25 mL/min to induce mild hypothermia. Twenty pairs of subjects conformed to strict matching and were finally included in the statistical analysis. The two groups of patients differed significantly in white blood cell count and percentage of neutrophils (p < 0.05); however, there were no significant differences in D-dimer, procalcitonin, and BNP levels. The two groups of patients did not differ significantly with respect to the incidence of the following indicators: upper gastrointestinal bleeding; pulmonary infection; venous thrombosis; vasospasms; seizures; and chills (p > 0.05). CONCLUSION: Mild therapeutic hypothermia in target vessels plus endovascular thrombectomy was shown to be safe in patients with acute large vessel occlusion cerebral infarction.

[Effect of high altitude hypoxia on fetal development during pregnancy and the reason analysis].

High altitude hypoxia is an important factor to affect fetal development during pregnancy. In the special environment, maternal physiological functions are regulated to maintain the maternal and fetal homeostasis, so that limited oxygen is to meet the needs of fetal growth and development. In this review, the literatures about the effects of hypoxic environment on fetal development during pregnancy in recent years were summarized, in which the fetal growth characteristics, maternal physiological regulation, genetic and placental influencing factors in high altitude areas were involved. This may be helpful for the reproductive healthcare of women in high altitude region, and also for the treatment and prevention of fetal growth retardation in the hypoxic environment.

Municipal sludge biochar skeletal sodium alginate beads for phosphate removal.

A novel Fe/La decorative biochar filled in sodium alginate beads (SA-KBC-Fe/La) was prepared by a simple sol-gel method and applied to adsorb phosphate (P) efficiently from water in this study. The morphology, structure and chemical component of the hydrogel beads were characterized in detail. And the synthesized bead exhibited easy separation and high P uptake of 46.65 mg/g when the Fe: La was of 1: 2 at 298 K with initial P of 100 mg/L, which was much higher than SA gel bead. The adsorption showed that the optimal pH was 6, and the adsorption was met with pseudo-second-order kinetics and Langmuir isothermal models, indicating a chemical adsorption process. The adsorption capacity remained 82 % after 5 cycles of adsorption. The adsorption mechanism of P was mainly of ligand exchange and electrostatic attraction. Compared with other reported adsorbents, the modification of Fe/La could enhance the mechanical property of SA-KBC-Fe/La beads with increasing active sites. Additionally, the involved biochar could lead to excellent thermal stability and hierarchical porous structure of beads with larger specific surface area (54.22 m2/g). The study could provide new ideas for P removal and strategy for the final disposal of municipal sludge.

Risk and mediation analyses of hemoglobin glycation index and survival prognosis in patients with sepsis.

An increasing number of studies have reported the close relation of the hemoglobin glycation index (HGI) with metabolism, inflammation, and disease prognosis. However, the prognostic relationship between the HGI and patients with sepsis remains unclear. Thus, this study aimed to analyze the association between the HGI and all-cause mortality in patients with sepsis using data from the MIMIC-IV database. In this study, 2605 patients with sepsis were retrospectively analyzed. The linear regression equation was established by incorporating glycated hemoglobin (HbA1c) and fasting plasma glucose levels. Subsequently, the HGI was calculated based on the difference between the predicted and observed HbA1c levels. Furthermore, the HGI was divided into the following three groups using X-tile software: Q1 (HGI ≤ - 0.50%), Q2 (- 0.49% ≤ HGI ≤ 1.18%), and Q3 (HGI ≥ 1.19%). Kaplan-Meier survival curves were further plotted to analyze the differences in 28-day and 365-day mortality among patients with sepsis patients in these HGI groups. Multivariate corrected Cox proportional risk model and restricted cubic spline (RCS) were used. Lastly, mediation analysis was performed to assess the factors through which HGI affects sepsis prognosis. This study included 2605 patients with sepsis, and the 28-day and 365-day mortality rates were 19.7% and 38.9%, respectively. The Q3 group had the highest mortality risk at 28 days (HR = 2.55, 95% CI: 1.89-3.44, p < 0.001) and 365 days (HR = 1.59, 95% CI: 1.29-1.97, p < 0.001). In the fully adjusted multivariate Cox proportional hazards model, patients in the Q3 group still displayed the highest mortality rates at 28 days (HR = 2.02, 95% CI: 1.45-2.80, p < 0.001) and 365 days (HR = 1.28, 95% CI: 1.08-1.56, p < 0.001). The RCS analysis revealed that HGI was positively associated with adverse clinical outcomes. Finally, the mediation effect analysis demonstrated that the HGI might influence patient survival prognosis via multiple indicators related to the SOFA and SAPS II scores. There was a significant association between HGI and all-cause mortality in patients with sepsis, and patients with higher HGI values had a higher risk of death. Therefore, HGI can be used as a potential indicator to assess the prognostic risk of death in patients with sepsis.

Erythrocytes Display Metabolic Changes in High-Altitude Polycythemia.

Qile, Muge, Qiying Xu, Yi Ye, Huifang Liu, Drolma Gomchok, Juanli Liu, Tana Wuren, and Ri-Li Ge. Erythrocytes display metabolic changes in high-altitude polycythemia. High Alt Med Biol. 24:104-109, 2023. Background: Sphingosine-1-phosphate (S1P) levels are increased after acute exposure to high altitude; however, whether this effect is observed in chronic high-altitude hypoxia is unknown. Methods: We studied erythrocyte S1P levels in 13 subjects with high-altitude polycythemia (HAPC) and 13 control subjects and also used a mouse model of HAPC. HAPC subjects lived in Maduo (4,300 m altitude) for 10 years, whereas control subjects lived permanently in Xining (2,260 m). The mouse model of HAPC was established by stimulating an altitude of 5,000 m in a hypobaric chamber for 30 days. Hematology and S1P, CD73, 2,3-bisphosphoglycerate (2,3-BPG), and reticulocyte levels were measured. Results: The hemoglobin concentration and number of red blood cells were significantly elevated in human and mouse HAPC groups. Blood S1P levels in HAPC subjects and mice were higher than those in control groups (p < 0.05 and p < 0.001, respectively). 2,3-BPG and CD73 levels in HAPC subjects were significantly higher than those in control subjects (p < 0.05). No significant changes in reticulocyte levels were observed. Conclusions: The critical altitude-induced metabolic changes such as S1P retained high levels even after prolonged exposure, and it may inspire future research into therapeutic strategies for hypoxia-associated illnesses.

Quantitative structure-toxicity relationships of halobenzoquinone isomers on DNA reactivity and genotoxicity.

Halobenzoquinones (HBQs) are an emerging class of drinking water disinfection byproducts that have been predicted as bladder carcinogens. However, data on the genotoxicity of HBQs are still scarce. This study performed a quantitative structure-toxicity relationship (QSTR) analysis of HBQ isomers on DNA reactivity and genotoxicity. The interaction of HBQs with calf thymus DNA (ct-DNA) was studied using multi-spectroscopic and molecular docking techniques. UV-Vis absorption spectra observed a significant hyperchromic effect with the increase of HBQ concentration. The fluorescence intensity of both probe-ct-DNA decreased with the increasing concentration of HBQs, indicating that the interaction mode between each HBQs and DNA was quite complicated, and there were both minor groove binding and intercalation binding. Molecular docking showed that HBQs interacted with DNA predominantly via hydrogen bond at guanine-rich areas in the minor groove of DNA. The genotoxicity of HBQs on human hepatocytes (L-02) was evaluated by micronucleus test, and the results showed that HBQs could cause significant chromosomal damage. The rank order of HBQ isomers on DNA reactivity and genotoxicity was 2,5-HBQs > their corresponding 2,6-HBQs. QSTR analysis found that dipole moment is the key structural descriptor influencing both DNA reactivity and genotoxicity of HBQ isomers. This study suggested that HBQs have caused genotoxicity which was influenced by their isomeric effects, warranting a comprehensive understanding of the genotoxic and carcinogenic risks associated with HBQs exposure.

Identification of a miRNA-mRNA Regulatory Networks in Placental Tissue Associated With Tibetan High Altitude Adaptation.

The Tibetan population has lived and successfully reproduced at high altitude for many generations. Studies have shown that Tibetans have various mechanisms for protection against high-altitude hypoxia, which are probably due, at least in part, to placental adaptation. However, comprehensive in silico analyses of placentas in Tibetans are lacking. We performed a microarray-based comparative transcriptome analysis of 10 Tibetan women from Yushu, Qinghai, CHN (∼3,780 m) and 10 European women living in Leadville, CO, United States (∼3,100 m) for less than three generations. Expression of HIF-1α, STAT3, EGFR, HSP5A, XBP1, and ATF6A mRNA was less in the Tibetan placentas as compared with European placentas. A total of 38 miRNAs were involved in regulating these genes. Differentially expressed genes were enriched for HIF1α signaling pathways, protein processing in the endoplasmic reticulum, PI3K-AKT signaling pathways, and MAPK signaling pathways. Based on the transcriptome profiles, the Tibetan population was distinct from the European population; placental tissues from the Tibetan population are lacking hypoxic responses, and "passivation" occurs in response to hypoxic stress. These results provide insights into the molecular signature of adaptation to high altitudes in these two populations.

Synthesis and electrochemical properties of various dimensional poly(1,5-diaminoanthraquinone) nanostructures: Nanoparticles, nanotubes and nanoribbons.

Nanostructured conducting polymers show their promising potential as electrode materials for supercapacitors. Here, chemical oxidation polymerization of 1,5-diaminoanthraquinone (DAA) was conducted with HClO4 as initiator and (NH4)2S2O8 as oxidant in different solvent systems. Due to the different solubilities of its oligomers, different poly(1,5-diaminoanthraquinone) (PDAA) nanostructures were obtained, such as nanoparticles, nanotubes and nanoribbons. As electrode materials, the PDAA nanotubes synthesized in 1:1 CH3CN/DMF mixture possessed the highest specific capacitance of 353 F/g at 1 A/g and the best rate capability with the capacitance retention of 52% even at 20 A/g in 1 M H2SO4 electrolyte, while the PDAA nanoparticles synthesized in DMF showed the best cycling stability of 111% of its initial capacitance after 10,000 CV cycles at 100 mV/s, despite the same chemical structure with different morphologies.

Well-defined poly(1,5-diaminoanthraquinone)/reduced graphene oxide hybrids with superior electrochemical property for high performance electrochemical capacitors.

Conducting polymers and their hybrids have attracted significant attention in electrochemical capacitors due to their unique electrochemical properties. However, the poorer cycle life and lower rate capability have greatly restricted their practical applications. Herein, well-defined poly(1,5-diaminoanthraquinone)/reduced graphene oxide hybrids (PDAA/rGO) with excellent electrochemical performance were successfully prepared via in-situ chemical oxidation polymerization of 1,5-diaminoanthraquinone (DAA) using HClO4 as initiator and (NH4)2S2O8 as oxidant in organic solvent mixture at room 25 °C. The electrochemical tests showed that the optimized one, PDAA/rGO S-2 with PDAA nanoparticles of 50 nm uniformly immobilized, possessed the specific capacitance of 617F g-1 at the current density of 1 A g-1 in 1.0 mol L-1 H2SO4 electrolyte and outstanding rate capability with the capacitance retention of 70% even at a high current density of 20 A g-1. Moreover, superior cycle life was achieved to about 124% of its initial capacitance at 100 mV s-1 after 15,000 cycles without attenuation, and the symmetric solid-state supercapacitor (SSC) based on the PDAA/rGO S-2 electrodes remained 79% of its initial specific capacitance after 15,000 CV cycles.

Poly(1,5-diaminoanthraquinone) coated carbon cloth composites as flexible electrode with extraordinary cycling stability for symmetric solid-state supercapacitors.

Poly(1,5-diaminoanthraquinone) (PDAA) coated carbon cloth (ROCC@PDAA) composites were fabricated as flexible electrode by in-situ chemical oxidation polymerization of 1,5-diaminoanthraquinone (DAA) on the surface of oxidized carbon cloth (OCC) using ammonium persulfate (APS) as oxidant in the mixture of N,N-dimethylformamide/acetonitrile by refluxing with HClO4 as initiator, followed by reducing the OCC with hydrazine. The optimized flexible composites possessed high areal capacitance of 1.3 F cm-2 (specific capacitance of 81.9 F g-1) at the current density of 1 mA cm-2 with excellent rate properties (61% at 20 mA cm-2) and extraordinary cycling stability (159% after 20,000 cycles). The flexible symmetric solid-state supercapacitor (SSC) constructed with the optimized ROCC@PDAA composite could light up a red light emitting diode, also exhibited excellent electrochemical performance with remarkable mechanical and flexible properties. All the results demonstrated the potential application of the proposed ROCC@PDAA composites for flexible energy storage devices.

A novel Biochar modified by Chitosan-Fe/S for tetracycline adsorption and studies on site energy distribution.

A novel wasted sludge-based Biochar modified by Chitosan and Fe/S (BCFe/S) was prepared for tetracycline (TC) removal from water. To investigate the similarities and differences in adsorption behaviors between Biochar and BCFe/S, characterization, kinetics, isotherms and thermodynamics were discussed. The studies on site energy distribution (SED) were also presented. The results showed that the maximum TC adsorption amount was 51.78 mg/g for Biochar, while it was 183.01 mg/g for BCFe/S-4. Meanwhile, electrostatic attraction, π-π stacking, pore filling, silicate bonding and hydrogen bonding were the main adsorption mechanisms for TC removal by Biochar. Besides above mechanisms, chelating and ion exchange were also accounted for adsorption mechanisms for TC uptake by BCFe/S-4. Moreover, SED results revealed that the surface of Biochar was more homogeneous while the surface of BCFe/S-4 was more heterogeneous at higher temperature. Findings of this work could offer valuable information in designing adsorbents and investigating adsorption mechanisms.

Identification and Characterization of a Cis Antisense RNA of the rpoH Gene of Salmonella enterica Serovar Typhi.

Antisense RNAs from complementary strands of protein coding genes regulate the expression of genes involved in many cellular processes. Using deep sequencing analysis of the Salmonella enterica serovar Typhi (S. Typhi) transcriptome, a novel antisense RNA encoded on the strand complementary to the rpoH gene was revealed. In this study, the molecular features of this antisense RNA were assessed using northern blotting and rapid amplification of cDNA ends. The 3,508 nt sequence of RNA was identified as the antisense RNA of the rpoH gene and was named ArpH. ArpH was found to attenuate the invasion of HeLa cells by S. Typhi by regulating the expression of SPI-1 genes. In an rpoH mutant strain, the invasive capacity of S. Typhi was increased, whereas overexpression of ArpH positively regulates rpoH mRNA levels. Results of this study suggest that the cis-encoded antisense RNA ArpH is likely to affect the invasive capacity of S. Typhi by regulating the expression of rpoH.

The plasma level changes of VEGF and soluble VEGF receptor-1 are associated with high-altitude pulmonary edema.

Hypoxia-induced plasma levels of VEGF and sFlt-1 are responsible for increased vascular permeability occurred in both brain and pulmonary edema. Currently, it remains unclear the exact roles of VEGF and sFlt-1 in High Altitude Pulmonary Edema (HAPE) pathogenesis. In this study, plasma levels of VEGF and sFlt-1 from 10 HAPE and 10 non-HAPE subjects were measured and compared. The results showed that plasma levels of both VEGF and sFlt-1 in HAPE patients were significantly increased as compared to the non-HAPE group. Interestingly, increased plasma levels of these two protein factors were markedly reduced after treatments. As compared to VEGF, sFlt-1 was much more affected by hypoxia and treatments, suggesting this factor was a key factor contributed to HAPE pathogenesis. Importantly, the ratio of sFlt-1 and VEGF in group of either non-HAPE or HAPE after recovery was significantly lower than the ratio in HAPE patients prior to treatments. Our findings suggested that sFlt-1 was a key factor that involved in HAPE pathogenesis and the sFlt-1/VEGF ratio could be used as a sensitive diagnostic marker for HAPE. J. Med. Invest. 65:64-68, February, 2018.

Photoredox catalysis enabled alkylation of alkenyl carboxylic acids with N-(acyloxy)phthalimide via dual decarboxylation.

A ruthenium based photoredox catalyst in combination with a substoichiometric amount of 1,4-diazabicyclo[2.2.2]octane (DABCO) efficiently catalyzed dual decarboxylative couplings between alkenyl carboxylic acids and N-(acyloxy)phthalimides derived from aliphatic carboxylic acids, delivering alkylated styrene derivatives in a high regio- and stereo-selective manner under mild reaction conditions. Various types of secondary, tertiary, and quaternary aliphatic carboxylic acids as well as α-amino acids can be used as suitable substrates. Mechanistic analysis suggested that the reaction proceeds through a radical mechanism mediated by a Ru(i)/Ru(ii) catalytic cycle with DABCO acting both as the base and the co-catalyst for single electron transfer.

An Ir-photoredox-catalyzed decarboxylative Michael addition of glyoxylic acid acetal as a formyl equivalent.

We reported herein an iridium-photoredox-catalyzed decarboxylative conjugated addition of glyoxylic acid acetals with various Michael acceptors, including unsaturated amide, ester, aldehyde, ketone, and nitrile under irradiation. Vinyl pyridine and α-aryl styrene are also suitable substrates. The reaction offers various types of acetal products, which are of synthetic significance as protected aldehydes.

[Startup, stable operation and process failure of EBPR system under the low temperature and low dissolved oxygen condition].

A sequencing batch reactor (SBR) was started up and operated with alternating anaerobic/oxic (An/O) to perform enhanced biological phosphorus removal (EBPR) under the condition of 13-16 degrees C. The results showed that under the condition of low temperature, the EBPR system was successfully started up in a short time (<6 d). The reactor achieved a high and stable phosphorus removal performance with an influent phosphate concentration of 20 mg x L(-1) and the dissolved oxygen (DO) concentration of 2 mg x L(-1). The effluent phosphate concentration was lower than 0.5 mg x L(-1). It was found that decreasing DO had an influence on the steady operation of EBPR system. As DO concentration of aerobic phase decreased from 2 mg x L(-1) to 1 mg x L(-1), the system could still perform EBPR and the phosphorus removal efficiency was greater than 97.4%. However, the amount of phosphate released during anaerobic phase was observed to decrease slightly compared with that of 2 mg x L(-1) DO condition. Moreover, the phosphorus removal performance of the system deteriorated immediately and the effluent phosphate concentration couldn't meet the national integrated wastewater discharge standard when DO concentration was further lowered to 0.5 mg x L(-1). The experiments of increasing DO to recover phosphorus removal performance of the EBPR suggested the process failure resulted from low DO was not reversible in the short-term. It was also found that the batch tests of anoxic phosphorus uptake using nitrite and nitrate as electron acceptors had an impact on the stable operation of EBPR system, whereas the resulting negative influence could be recovered within 6 cycles. In addition, the mixed liquid suspended solids (MLSS) of the EBPR system remained stable and the sludge volume index (SVI) decreased to a certain extend in a long run, implying long-term low temperature and low DO condition favored the sludge sedimentation.