A novel alternavirus with three dsRNA segments from Fusarium pseudograminearum, the pathogen of Fusarium crown rot in wheat.

Three dsRNA segments were detected in Fusarium pseudograminearum strain CF14029, a pathogen causing Fusarium crown rot in China. Characterization and sequence analysis confirmed that these dsRNA sequences originated from the same virus. The viral genome consists of three dsRNA segments: dsRNA1 (3,560 nt in length), encoding an RNA-dependent RNA polymerase (RdRp), dsRNA2 (2,544 nt in length), encoding a hypothetical protein, and dsRNA3 (2,478 nt in length), encoding a putative coat protein (CP). Phylogenetic analysis based on the RdRp and CP amino acid sequences revealed a high degree of similarity of this virus to members of the genus Alternavirus, family Alternaviridae, isolated from other Fusarium fungi. As a novel member of the genus Alternavirus, this virus was provisionally named "Fusarium pseudograminearum alternavirus 1" (FpgAV1). Like other alternaviruses found in Fusarium species, the positive-sense strand of each genomic dsRNA of FpgAV1 possesses a poly(A) tail and a distinctive 5'-terminal octamer sequence (5'-GCT GTG TG-3'). This is the first report of the genomic sequence of an alternavirus identified in F. pseudograminearum.

Study on the effect of protein lysine lactylation modification in macrophages on inhibiting periodontitis in rats.

BACKGROUND: Protein lysine lactylation (Kla) has been proved to be closely related to inflammatory diseases, but its role in periodontitis (PD) is unclear. Therefore, this study aimed to establish the global profiling of Kla in PD models in rats. METHODS: Clinical periodontal samples were collected, the inflammatory state of tissues was verified by H&E staining, and lactate content was detected by a lactic acid kit. Kla levels were detected by immunohistochemistry (IHC) and Western blot. Subsequently, the rat model of PD was developed and its reliability verified by micro-CT and H&E staining. Mass spectrometry analysis was conducted to explore the expression profile of proteins and Kla in periodontal tissues. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed, and a protein-protein interaction (PPI) network was constructed. The lactylation in RAW264.7 cells was confirmed by IHC, immunofluorescence and Western blot. The relative expression levels of inflammatory factors IL-1ß, IL-6, TNF-α, macrophage polarization-related factors CD86, iNOS, Arg1, and CD206 in RAW264.7 cells were detected by real time-quantitative polymerase chain reaction (RT-qPCR). RESULTS: We observed substantial inflammatory cell infiltration in the PD tissues, and the lactate content and lactylation levels were significantly increased. The expression profiles of protein and Kla were obtained by mass spectrometry based on the established rat model of PD. Kla was confirmed in vitro and in vivo. After inhibiting the "writer" of lactylation P300 in RAW264.7 cells, the lactylation levels decreased, and the expression of inflammatory factors IL-1ß, IL-6, and TNF-α increased. Meanwhile, the levels of CD86 and iNOS increased, and Arg1 and CD206 decreased. CONCLUSIONS: Kla may play an important role in PD, regulating the release of inflammatory factors and polarization of macrophages.

Fabrication and characterization of ZnGa1.01Te2.13/g-C3N4 heterojunction with enhanced photocatalytic activity.

The extensive consumption of fossil fuels increases CO2 concentration in the atmosphere, resulting in serious global warming problems. Meanwhile, the problem of water contamination by organic substances is another significant global challenge. We have successfully synthesized ZnGa1.01Te2.13/g-C3N4 (ZGT/GCN) composites for the first time as effective photocatalysts for both pollutant degradation and CO2 reduction. ZGT/GCN composites were synthesized by a simple hydrothermal method. The prepared photocatalysts were characterized by XRD, SEM, TEM-EDS, DRS, BET, PL, and XPS. The ZGT/GCN heterojunction exhibited considerably enhanced photocatalytic activity in the degradation of crystal violet (CV) as well as in the photoreduction of CO2 when compared to pure ZGT and GCN semiconductors. The optimal rate constant for CV degradation was obtained with the ZGT-80%GCN composite (0.0442 h-1), which is higher than the constants obtained with individual ZGT and GCN by 7.75 and 1.63 times, respectively. Moreover, the CO2 reduction yields into CH4 by ZGT-80%GCN was 1.013 µmol/g in 72 h, which is 1.21 and 1.08 times larger than the yields obtained with ZGT and GCN. Scavenger and ESR tests were used to propose the photocatalytic mechanism of the ZGT/GCN composite as well as the active species in the CV degradation.

Nano-Selenium inhibited antibiotic resistance genes and virulence factors by suppressing bacterial selenocompound metabolism and chemotaxis pathways in animal manure.

Numerous antibiotic resistance genes (ARGs) and virulence factors (VFs) found in animal manure pose significant risks to human health. However, the effects of graphene sodium selenite (GSSe), a novel chemical nano-Selenium, and biological nano-Selenium (BNSSe), a new bioaugmentation nano-Se, on bacterial Se metabolism, chemotaxis, ARGs, and VFs in animal manure remain unknown. In this study, we investigated the effects of GSSe and BNSSe on ARGs and VFs expression in broiler manure using high-throughput sequencing. Results showed that BNSSe reduced Se pressure during anaerobic fermentation by inhibiting bacterial selenocompound metabolism pathways, thereby lowering manure Selenium pollution. Additionally, the expression levels of ARGs and VFs were lower in the BNSSe group compared to the Sodium Selenite and GSSe groups, as BNSSe inhibited bacterial chemotaxis pathways. Co-occurrence network analysis identified ARGs and VFs within the following phyla Bacteroidetes (genera Butyricimonas, Odoribacter, Paraprevotella, and Rikenella), Firmicutes (genera Lactobacillus, Candidatus_Borkfalkia, Merdimonas, Oscillibacter, Intestinimonas, and Megamonas), and Proteobacteria (genera Desulfovibrio). The expression and abundance of ARGs and VFs genes were found to be associated with ARGs-VFs coexistence. Moreover, BNSSe disruption of bacterial selenocompound metabolism and chemotaxis pathways resulted in less frequent transfer of ARGs and VFs. These findings indicate that BNSSe can reduce ARGs and VFs expression in animal manure by suppressing bacterial selenocompound metabolism and chemotaxis pathways.

Gene Profiling of the Ascorbate Oxidase Family Genes under Osmotic and Cold Stress Reveals the Role of AnAO5 in Cold Adaptation in Ammopiptanthus nanus.

The uplift of the Qinghai Tibet Plateau has led to a drastic change in the climate in Central Asia, from warm and rainy, to dry and less rainfall. Ammopiptanthus nanus, a rare evergreen broad-leaved shrub distributed in the temperate desert region of Central Asia, has survived the drastic climate change in Central Asia caused by the uplift of the Qinghai-Tibet Plateau. Ascorbate oxidase (AO) regulates the redox status of the apoplast by catalyzing the oxidation of ascorbate acid to dehydroascorbic acid, and plays a key role in the adaptation of plants to environmental changes. Analyzing the evolution, environmental response, and biological functions of the AO family of A. nanus is helpful for understanding how plant genome evolution responds to climate change in Central Asia. A total of 16 AOs were identified in A. nanus, all of which contained the ascorbate oxidase domain, most of which contained transmembrane domain, and many were predicted to be localized in the apoplast. Segmental duplication and tandem duplication are the main factors driving the gene amplification of the AO gene family in A. nanus. Gene expression analysis based on transcriptome data and fluorescence quantitative PCR, as well as enzyme activity measurements, showed that the expression levels of AO genes and total enzyme activity decreased under short-term osmotic stress and low-temperature stress, but the expression of some AO genes (AnAO5, AnAO13, and AnAO16) and total enzyme activity increased under 7 days of cold stress. AnAO5 and AnAO11 are targeted by miR4415. Further functional studies on AnAO5 showed that AnAO5 protein was localized in the apoplast. The expression of AnAO5 in yeast cells and the transient expression in tobacco enhanced the tolerance of yeast and tobacco to low-temperature stress, and the overexpression of AnAO5 enhanced the tolerance of Arabidopsis seedlings to cold stress. Our research provides important data for understanding the role of AOs in plant adaptation to environmental change.

Deep Reinforcement Learning for Traffic Signal Control Model and Adaptation Study.

Deep reinforcement learning provides a new approach to solving complex signal optimization problems at intersections. Earlier studies were limited to traditional traffic detection techniques, and the obtained traffic information was not accurate. With the advanced in technology, we can obtain highly accurate information on the traffic states by advanced detector technology. This provides an accurate source of data for deep reinforcement learning. There are many intersections in the urban network. To successfully apply deep reinforcement learning in a situation closer to reality, we need to consider the problem of extending the knowledge gained from the training to new scenarios. This study used advanced sensor technology as a data source to explore the variation pattern of state space under different traffic scenarios. It analyzes the relationship between the traffic demand and the actual traffic states. The model learned more from a more comprehensive state space of traffic. This model was successful applied to new traffic scenarios without additional training. Compared our proposed model with the popular SAC signal control model, the result shows that the average delay of the DQN model is 5.13 s and the SAC model is 6.52 s. Therefore, our model exhibits better control performance.

Molecular characterization of a novel botourmiavirus with inverted complementary termini from the rice blast fungus Magnaporthe oryzae isolate HF04.

A novel positive-sense single-stranded RNA mycovirus, designated as "Magnaporthe oryzae botourmiavirus 10" (MoBV10), was identified in the rice blast fungus Magnaporthe oryzae isolate HF04. MoBV10 has a single genomic RNA segment consisting of 2,448 nucleotides, which contains a single open reading frame encoding an RNA-dependent RNA polymerase. Genome comparison and phylogenetic analysis indicated that MoBV10 is a new member of the genus Betascleroulivirus in the family Botourmiaviridae. The 5'- and 3'-terminal sequences of the genomic RNA of MoBV10 have inverted complementarity and potentially form a panhandle structure, which is very rare in RNA viruses.

Photoreduction of carbon dioxide and photodegradation of organic pollutants using alkali cobalt oxides MCoO2 (M = Li or Na) as catalysts.

The recycling of lithium batteries should be prioritized, and the use of discarded alkali metal battery electrode materials as photocatalysts merits research attention. This study synthesized alkali metal cobalt oxide (MCoO2, M = Li or Na) as a photocatalyst for the photoreduction of CO2 and degradation of toxic organic substances. The optimized NaCoO2 and LiCoO2 photocatalysts increased the photocatalytic CO2-CH4 conversion rate to 21.0 and 13.4 µmol g-1 h-1 under ultraviolet light irradiation and to 16.2 and 5.3 µmol g-1 h-1 under visible light irradiation, which is 17 times higher than that achieved by TiO2 P25. The rate constants of the optimized reactions of crystal violet (CV) with LiCoO2 and NaCoO2 were 2.29 × 10-2 and 4.35 × 10-2 h-1, respectively. The quenching effect of the scavengers and electron paramagnetic resonance in CV degradation indicated that active O2•-, 1O2, and h+ play the main role, whereas •OH plays a minor role for LiCoO2. The hyperfine splitting of the DMPO-•OH and DMPO-•CH3 adducts was aN = 1.508 mT, aHß = 1.478 mT and aN = 1.558 mT, aHß = 2.267 mT, respectively, whereas the hyperfine splitting of DMPO+• was aN = 1.475 mT. The quenching effect also indicated that active O2•- and h+ play the main role and that •OH and 1O2 play a minor role for NaCoO2. The hyperfine splitting of the DMPO-•OH and DMPO+• adducts was aN = 1.517 mT, aHß = 1.489 mT and aN = 1.496 mT, respectively. Discarded alkali metal battery electrode materials can be reused as photocatalysts to address environmental pollution.

Controlled hydrothermal synthesis of BiOxCly/BiOmBrn/g-C3N4 composites exhibiting visible-light photocatalytic activity.

The first systematic synthesis of bismuth oxychloride/bismuth oxybromide/graphitic carbon nitride (BiOxCly/BiOmBrn/g-C3N4) nano-composites used a controlled hydrothermal method. The structure, morphology and characteristic of BiOxCly/BiOmBrn/g-C3N4 photocatalyst were measured by XRD, UV-vis-DRS, FT-IR, FE-TEM, FE-SEM-EDS, PL, BET, HR-XPS and EPR. Under visible light irradiation, the photodegradation activity was evaluated for the decolorization of crystal violet (CV) and 2-hydroxybenzoic acid (2-HBA) in aqueous solution. The catalytic performance showed that, when using sample BB2C1-4-250-30 wt% g-C3N4 composite as a photocatalyst, the best reaction-rate-constant (k) was 0.071 h-1. It was 1.5 times higher than the k value of BB2C1-4-250 as a photocatalyst. From the scavenging effect of various scavengers, the results of EPR showed that reactive OH was the main scavenger, while O2-, h+ and 1O2 were the second scavenger in CV degradation. In this study, a possible photodegradation mechanism was proposed and discussed. In this work, our method of BiOxCly/BiOmBrn/g-C3N4 preparation could be used for future mass production and the BiOxCly/BiOmBrn/g-C3N4 composite materials could be applied to the environmental pollution control in future.

Visible-light-driven photocatalysis of carbon dioxide and organic pollutants by MFeO2 (M = Li, Na, or K).

In recent years, lithium-containing ceramic materials have attracted considerable research attention as high-temperature adsorbents of carbon dioxide. The recycling of electrode materials from spent lithium-ion batteries for use as photocatalysts in recovering CO2 and degrading organic pollutants is worthy of exploration. Solid, magnetic ferrite-containing photocatalysts are easily separated from reaction solutions by using magnetic devices. Solid catalysts (e.g., LiFeO2, LiFe5O8, NaFeO2, and K2Fe2O4) were prepared through the calcination of Fe2O3 and M2CO3. CO2 was photoreduced and crystal violet (CV) and 2-hydroxybenzoic acid (2-HBA) were photodegraded under visible light irradiation. The optimized K2Fe2O4 photocatalyst increased the rate of photocatalytic conversion from CO2 to methane at 20.9 µmol g-1 h-1. The catalytic efficiency indicated that the optimized reaction rate constants of CV with LiFeO2, NaFeO2, and K2Fe2O4 were 2.98 × 10-1, 5.32 × 10-1, and 4.36 × 10-1 h-1, respectively. The quenching effect achieved through the use of various scavengers and the electron paramagnetic resonance in CV degradation revealed the substantial contribution of the reactive superoxide anion radical O2- and the minor roles of h+ and the OH radical. Its usefulness in the synthesis of solid-base catalyst MFeO2 is promising for environmental control and relevant applications, particularly in solar energy manufacturing.

Temperature-Responded Biological Fitness of Carbendazim-Resistance Fusarium graminearum Mutants Conferring the F167Y, E198K, and E198L Substitutions.

Understanding the effects of temperature on Fusarium graminearum infection can provide theoretical guidance for chemical control of Fusarium head blight (FHB). Here, we evaluated the effects of various temperatures on biological fitness development of wild-type sensitive strain 2021 and carbendazim-resistance mutants conferring ß2-tubulin substitutions F167Y, E198K, and E198L. The results showed that mycelial growth and conidiation of four strains increased with the increase in temperature between 10 and 25°C. Conidia of F167Y displayed strong adaptability to low temperature. The virulence of the four strains was largely similar at the same temperature, showing an upward trend between 10 and 25°C. At 10°C, the hyphal growth of all strains was significantly inhibited, metabolism was slowed down, and the accumulation of secondary metabolites decreased. Subsequently, the production of deoxynivalenol (DON) and its intermediates pyruvate and aurofusarin decreased at low temperature, and the expression of DON biosynthesis-related genes Tri5, FgPK, and AUR decreased accordingly. At the same temperature, the aurofusarin production of the strains F167Y and E198K was higher than that of strains 2021 and E198L. The contents of DON and pyruvic acid in carbendazim-resistance mutants were higher than those in the wild-type strain 2021. The sensitivity of four strains to different fungicides changed at various temperatures. The sensitivity to most fungicides increased with decreasing temperature. The carbendazim-resistance mutants showed positive cross-resistance with other benzimidazoles. However, there was no cross-resistance to pyraclostrobin and azoles. These results would direct us to use fungicides preventing the infection of F. graminearum with changeable atmospheric temperature at the wheat flower stage.

Author Correction: Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys.

Following the publication of our paper (Zhang et al., 2020), it has come to our attention that we erroneously listed two funding sources unrelated to this study in the "ACKNOWLEDGEMENTS" section. Hereby, we wish to update the "ACKNOWLEDGEMENTS" section as a correction.

Neuroprotectants attenuate hypobaric hypoxia-induced brain injuries in cynomolgus monkeys.

Hypobaric hypoxia (HH) exposure can cause serious brain injury as well as life-threatening cerebral edema in severe cases. Previous studies on the mechanisms of HH-induced brain injury have been conducted primarily using non-primate animal models that are genetically distant to humans, thus hindering the development of disease treatment. Here, we report that cynomolgus monkeys ( Macacafascicularis) exposed to acute HH developed human-like HH syndrome involving severe brain injury and abnormal behavior. Transcriptome profiling of white blood cells and brain tissue from monkeys exposed to increasing altitude revealed the central role of the HIF-1 and other novel signaling pathways, such as the vitamin D receptor (VDR) signaling pathway, in co-regulating HH-induced inflammation processes. We also observed profound transcriptomic alterations in brains after exposure to acute HH, including the activation of angiogenesis and impairment of aerobic respiration and protein folding processes, which likely underlie the pathological effects of HH-induced brain injury. Administration of progesterone (PROG) and steroid neuroprotectant 5α-androst-3ß,5,6ß-triol (TRIOL) significantly attenuated brain injuries and rescued the transcriptomic changes induced by acute HH. Functional investigation of the affected genes suggested that these two neuroprotectants protect the brain by targeting different pathways, with PROG enhancing erythropoiesis and TRIOL suppressing glutamate-induced excitotoxicity. Thus, this study advances our understanding of the pathology induced by acute HH and provides potential compounds for the development of neuroprotectant drugs for therapeutic treatment.

Lead bismuth oxybromide/graphene oxide: Synthesis, characterization, and photocatalytic activity for removal of carbon dioxide, crystal violet dye, and 2-hydroxybenzoic acid.

A novel lead bismuth oxybromide/graphene oxide (PbBiO2Br/GO) composite photocatalyst were prepared using a controlled and nontemplate hydrothermal technique with PbBiO2Br and GO as the starting material. The heterojunction photocatalysts were characterized through XRD, FE-SEM-EDS, HR-TEM, XPS, DR-UV-vis, BET, PL, EPR, and UPS. Under the optimal synthesis conditions, the photocatalytic activity of PbBiO2Br/GO composites was much higher than that of PbBiO2Br. Under 25 °C, 1 atm, and 432-nm visible light irradiation at, the optimized PbBiO2Br/GO increased the rate (at 1.913 µmol g-1 h-1) of photocatalytic conversion from carbon dioxide (CO2) to methane (CH4). This conversion rate was higher than that of the original PbBiO2Br material (0.957 µmol g-1 h-1). Therefore, PbBiO2Br/GO is superior for CH4 production and has great potential as CO2 photoreduction catalysts. In addition, such catalytic performance (when using 0.05 wt%-GO/PbBiO2Br composite as a photocatalyst) indicates that the optimal reaction rate constants of crystal violet (CV) and 2-hydroxybenzoic acid (2-HBA) are 0.1278 and 0.0093 h-1, respectively, which are 1.82 and 1.24 times the reaction rate constant of PbBiO2Br as a photocatalyst, respectively. Our findings are useful for PbBiO2Br/GO synthesis and in its future environmental applications, particularly in solar fuel manufacture.

Magnesium protects mouse hippocampal HT22 cells against hypoxia-induced injury by upregulation of miR-221.

Magnesium (Mg2+ ) has been shown to exert neuroprotective effects against hypoxia. However, it still remains elusive whether Mg2+ protected mouse hippocampal HT22 cells against hypoxia-evoked damages. Therefore, we aimed to investigate the function of Mg2+ and mechanisms associated with microRNA-221 (miR-221). HT22 cells were exposed to 3% O2 for 24 hours to induce hypoxic damages with 21% as a normoxic culture condition. The damages were monitored by viability, migration, and apoptosis of HT22 cells with or without Mg2+ pretreatment. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was applied to examine the alteration of miR-221, miR-210, and miR-17-5p. Transduction was carried out to artificially alter the expression of miR-221 and nerve growth factor (NGF), which was confirmed by qRT-PCR or Western blot assays. To blunt phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and nuclear factor κB (NF-κB), LY294002 (10 µM) and BAY 11-7082 (10 µM) were used. We observed Mg2+ protected HT22 cells against hypoxia-induced damages by upregulating miR-221. Further, miR-221 positively regulated NGF expression. Overexpression of NGF alleviated cell injury, while suppression of NGF aggravated cell injury. Moreover, miR-221 elevated NGF by inducing phosphorylation of regulators in PI3K/AKT and NF-κB transduction cascades and then alleviated cell injury. In conclusion, Mg2+ protected HT22 cells against hypoxia-induced damages by upregulation of miR-221 and NGF. These findings provided insights into the development of improved strategies for clinical application.

Bismuth oxyfluoride/bismuth oxyiodide nanocomposites enhance visible-light-driven photocatalytic activity.

This is the first paper to report a series of bismuth oxyfluoride/bismuth oxyiodide (BiOpFq/BiOxIy) nanocomposites with different F/I molar ratios, pH values, and reaction temperatures that were synthesized through a template-free and controlled hydrothermal method. These nanocomposites were characterized through scanning electron microscope energy dispersive microscopy (SEM-EDS), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier-transform infrared (FT-IR), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller (BET), and diffuse reflectance spectroscopy (DRS). Under visible-light irradiation, the BiOpFq/BiOxIy composites exhibited excellent photocatalytic activities in the degradation of crystal violet (CV) and 2-hydroxybenzoic acid (HBA). The order of rate constants was BiOF/BiOI > BiOI ≫ BiOF. The photocatalytic activity of BiOF/BiOI composites reached a maximum rate constant of 0.2305 h-1, 1.2 times higher than that of BiOI and 100 times higher than that of BiOF. Thus, the derived BiOF/BiOI is crucial for photocatalytic activity enhancement. After the removal of CV in the third cycle, no apparent deficits in photocatalytic activity were observed, and the observed deficit was 8.2% during the fifth run. Overall, the catalytic activity and stability observed for the proposed composites were determined to be adequate under visible-light irradiation. For various scavengers, the noted quenching effects demonstrated that reactive O2- has a notable role in the degradation of the applied CV.

[Nitrogen Removal Effect and Conversion Characteristics of Nitrous Oxide in Single-stage and Multi-stage A/O Processes].

The single-stage A/O and multi-stage A/O processes were simulated by sequencing batch reactors (SBRs) with alternate stirring and aeration. The removal efficiency of nitrogen and the release mechanism of N2O were studied under the identical conditions of influent quality, hydraulic retention time (HRT), sludge retention time(SRT), temperature and anoxic/oxic (A/O) retention time ratio. Experimental results showed that COD or ammonia-nitrogen removal had no significant difference between the single-stage and the multi-stage A/O processes for the influent quality equivalent to municipal wastewater. However, TN removal efficiency of the former was better than the later with 72.1% and 52.2%, respectively. In the conversion of total nitrogen, during the typical cycle in the single-stage A/O and multi-stage A/O processes, the yields of N2O were 16.95 mg and 3.95 mg, respectively. The conversion rate, which is the ratio of N2O yield and TN removal, was respectively 11.47% and 4.11%. N2O production and emission occurred mainly in aerobic (nitrification) phase while there was little N2O emission in anoxic (denitrification) phase. Although the dominant species of AOB was both Nitrosomonas in the single-stage A/O and the multi-stage A/O processes under the same operating conditions, it was more conducive to the growth of nitrifying bacteria (AOB, NOB) in the single-stage A/O process with the greater abundance of Nitrosomonas. Meanwhile, the type and abundance of NOB in the single-stage A/O process were significantly more than in the multi-stage A/O process too. Therefore, it is more competitive to deal with the high-strengthening ammonia-nitrogen wastewater in the single-stage A/O process. In the actual operation of wastewater treatment, using appropriate partitions of A/O or oxygen-supplying modes can not only result in better nitrogen removal but also decrease the secondary pollution caused by N2O to the atmosphere.

Intermittent Oxygen Inhalation with Proper Frequency Improves Overall Health Conditions and Alleviates Symptoms in a Population at High Risk of Chronic Mountain Sickness with Severe Symptoms.

BACKGROUND: Oxygen inhalation therapy is essential for the treatment of patients with chronic mountain sickness (CMS), but the efficacy of oxygen inhalation for populations at high risk of CMS remains unknown. This research investigated whether oxygen inhalation therapy benefits populations at high risk of CMS. METHODS: A total of 296 local residents living at an altitude of 3658 m were included; of which these were 25 diagnosed cases of CMS, 8 cases dropped out of the study, and 263 cases were included in the analysis. The subjects were divided into high-risk (180 ≤ hemoglobin (Hb) <210 g/L, n = 161) and low-risk (Hb <180 g/L, n = 102) groups, and the cases in each group were divided into severe symptom (CMS score ≥6) and mild symptom (CMS score 0-5) subgroups. Severe symptomatic population of either high- or low-risk CMS was randomly assigned to no oxygen intake group (A group) or oxygen intake 7 times/week group (D group); mild symptomatic population of either high- or low-risk CMS was randomly assigned to no oxygen intake group (A group), oxygen intake 2 times/week group (B group), and 4 times/week group (C group). The courses for oxygen intake were all 30 days. The CMS symptoms, sleep quality, physiological biomarkers, biochemical markers, etc., were recorded on the day before oxygen intake, on the 15th and 30th days of oxygen intake, and on the 15th day after terminating oxygen intake therapy. RESULTS: A total of 263 residents were finally included in the analysis. Among these high-altitude residents, CMS symptom scores decreased for oxygen inhalation methods B, C, and D at 15 and 30 days after oxygen intake and 15 days after termination, including dyspnea, palpitation, and headache index, compared to those before oxygen intake (B group: Z = 5.604, 5.092, 5.741; C group: Z = 4.155, 4.068, 4.809; D group: Z = 6.021, 6.196, 5.331, at the 3 time points respectively; all P < 0.05/3 vs. before intake). However, dyspnea/palpitation (A group: Z = 5.003, 5.428, 5.493, both P < 0.05/3 vs. before intake) and headache (A group: Z = 4.263, 3.890, 4.040, both P < 0.05/3 vs. before intake) index decreased significantly also for oxygen inhalation method A at all the 3 time points. Cyanosis index decreased significantly 30 days after oxygen intake only in the group of participants administered the D method (Z = 2.701, P = 0.007). Tinnitus index decreased significantly in group A and D at 15 days (A group: Z = 3.377, P = 0.001, D group: Z = 3.150, P = 0.002), 30 days after oxygen intake (A group: Z = 2.836, P = 0.005, D group: Z = 5.963, P < 0.0001) and 15 days after termination (A group: Z = 2.734, P = 0.006, D group: Z = 4.049, P = 0.0001), and decreased significantly in the group B and C at 15 days after termination (B group: Z = 2.611, P = 0.009; C group: Z = 3.302, P = 0.001). In the population at high risk of CMS with severe symptoms, oxygen intake 7 times/week significantly improved total symptom scores of severe symptoms at 15 days (4 [2, 5] vs. 5.5 [4, 7], Z = 2.890, P = 0.005) and 30 days (3 [1, 5] vs. 5.5 [2, 7], Z = 3.270, P = 0.001) after oxygen intake compared to no oxygen intake. In the population at high risk of CMS with mild symptoms, compared to no oxygen intake, oxygen intake 2 or 4 times/week did not improve the total symptom scores at 15 days (2 [1, 3], 3 [1, 4] vs. 3 [1.5, 5]; χ2 = 2.490, P = 0.288), and at 30 days (2 [0, 4], 2 [1, 4.5] vs. 3 [2, 5]; χ2 = 3.730, P = 0.155) after oxygen intake. In the population at low risk of CMS, oxygen intake did not significantly change the white cell count and red cell count compared to no oxygen intake, neither in the severe symptomatic population nor in the mild symptomatic population. CONCLUSIONS: Intermittent oxygen inhalation with proper frequency might alleviate symptoms in residents at high altitude by improving their overall health conditions. Administration of oxygen inhalation therapy 2-4 times/week might not benefit populations at high risk of CMS with mild CMS symptoms while administration of therapy 7 times/week might benefit those with severe symptoms. Oxygen inhalation therapy is not recommended for low-risk CMS populations.

Metabolite Modulation in Human Plasma in the Early Phase of Acclimatization to Hypobaric Hypoxia.

The exposure of healthy subjects to high altitude represents a model to explore the pathophysiology of diseases related to tissue hypoxia. We explored a plasma metabolomics approach to detect alterations induced by the exposure of subjects to high altitude. Plasma samples were collected from 60 subjects both on plain and at high altitude (5300 m). Metabolite profiling was performed by gas chromatography-mass spectrometry (GC-MS) and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS) in conjunction with univariate and multivariate statistical analyses. ELISA assays were further employed to measure the levels of several relevant enzymes together with perturbed metabolic pathways. The results showed that hypobaric hypoxia caused significant and comprehensive metabolic changes, as represented by significant changes of 44 metabolites and 4 relevant enzymes. Using MetaboAnalyst 3.0, it was found that several key metabolic pathways were acutely perturbed. In addition, 5 differentially expressed metabolites in pre-exposure samples from the acute mountain sickness-susceptible (AMS-S) group compared with those from the AMS-resistant (AMS-R) group are identified, which warrant further validation as potential predictive biomarkers for AMS-S individuals. These results provide new insights for further understanding the pathophysiological mechanism of early acclimatization to hypobaric hypoxia and other diseases correlated to tissue hypoxia.

Interaction of CARD14, SENP1 and VEGFA polymorphisms on susceptibility to high altitude polycythemia in the Han Chinese population at the Qinghai-Tibetan Plateau.

High altitude polycythemia (HAPC) is a serious public health problem among Han Chinese immigrants to the Qinghai-Tibetan Plateau. This study aims to explore the genetic basis of HAPC in the Han Chinese population. 484 male subjects (234 patients and 250 controls) were enrolled in this study. Genotyping was performed for polymorphisms of I/D in ACE, C1772T and G1790A in exon 12 of HIF-1α, rs2567206 in CYP1B1, rs726354 in SENP1, rs3025033 in VEGFA, rs7251432 in HAMP, rs2075800 in HSPA1L and rs8065364 in CARD14. Gene-gene interaction was assessed by multifactor dimensionality reduction. A significant association was seen between CARD14 polymorphism rs8065364 and risk of HAPC development in male Han Chinese, and the C allele of rs8065364 was a risk factor (odds ratio (OR)=1.59, 95% confidence interval (95% CI)=1.21-2.08). Gene-gene interaction analysis indicated that a synergistic relationship existed between rs3025033 and rs8065364 (1.00%), rs3025033 and rs726354 (0.18%), and rs726354 and rs8065364 (0.17%). The combination of rs8065364 in CARD14, rs3025033 in VEGFA and rs726354 in SENP1 was the best model to predict HAPC development in this study (testing accuracy=0.6183, p=0.0010, cross-validated consistency=10/10). Genetic interactions of SNPs in CARD14, SENP1 and VEGFA might represent a functional mechanism in the pathogenesis of HAPC.