Regulatory loops between rice transcription factors OsNAC25 and OsNAC20/26 balance starch synthesis.

Several starch synthesis regulators have been identified, but these regulators are situated in the terminus of the regulatory network. Their upstream regulators and the complex regulatory network formed between these regulators remain largely unknown. A previous study demonstrated that NAM, ATAF, and CUC (NAC) transcription factors, OsNAC20 and OsNAC26 (OsNAC20/26), redundantly and positively regulate the accumulation of storage material in rice (Oryza sativa) endosperm. In this study, we detected OsNAC25 as an upstream regulator and interacting protein of OsNAC20/26. Both OsNAC25 mutation and OE resulted in a chalky seed phenotype, decreased starch content, and reduced expression of starch synthesis-related genes, but the mechanisms were different. In the osnac25 mutant, decreased expression of OsNAC20/26 resulted in reduced starch synthesis; however, in OsNAC25-overexpressing plants, the OsNAC25-OsNAC20/26 complex inhibited OsNAC20/26 binding to the promoter of starch synthesis-related genes. In addition, OsNAC20/26 positively regulated OsNAC25. Therefore, the mutual regulation between OsNAC25 and OsNAC20/26 forms a positive regulatory loop to stimulate the expression of starch synthesis-related genes and meet the great demand for starch accumulation in the grain filling stage. Simultaneously, a negative regulatory loop forms among the 3 proteins to avoid the excessive expression of starch synthesis-related genes. Collectively, our findings demonstrate that both promotion and inhibition mechanisms between OsNAC25 and OsNAC20/26 are essential for maintaining stable expression of starch synthesis-related genes and normal starch accumulation.

Ecological distribution and function of comammox Nitrospira in the environment.

Complete ammonia oxidizers (Comammox) are of great significance for studying nitrification and expanding the understanding of the nitrogen cycle. Moreover, Comammox bacteria are also crucial in natural and engineered environments due to their role in wastewater treatment and maintaining the flux of greenhouse gases to the atmosphere. However, only few studies are there regarding the Comammox bacteria and their role in ammonia and nitrite oxidation in the environment. This review mainly focuses on summarizing the genomes of Nitrospira in the NCBI database. Ecological distribution of Nitrospira was also reviewed and the influence of environmental parameters on genus Nitrospira in different environments has been summarized. Furthermore, the role of Nitrospira in carbon cycle, nitrogen cycle, and sulfur cycle were discussed, especially the comammox Nitrospira. In addition, the overviews of current research and development regarding comammox Nitrospira, were summarized along with the scope of future research. KEY POINTS: • Most of Comammox Nitrospira are widely distributed in both aquatic and terrestrial ecosystems, but it has been studied less frequently in the extreme environments. • Comammox Nitrospira can be involved in different nitrogen transformation process, but rarely involved in nitrogen fixation. • The stable isotope and transcriptome techniques are important methods to study the metabolic function of comammox Nitrospira.

NIR-II-absorbing diimmonium polymer agent achieves excellent photothermal therapy with induction of tumor immunogenic cell death.

Photothermal therapy has shown great promise for cancer treatment and second near-infrared (NIR-II) -absorbing particles could further improve its precision and applicability due to its superior penetration depth and new imaging ability. Herein, high NIR-II-absorbing polymer particles were prepared by using soluble isobutyl-substituted diammonium borates (P-IDI). The P-IDI showed stronger absorption at 1000-1100 nm, which exhibited excellent photostability, strong photoacoustic imaging ability and high photothermal conversion efficiency (34.7%). The investigations in vitro and in vivo demonstrated that the excellent photothermal effect facilitated complete tumor ablation and also triggered immunogenic cell death in activation of the immune response. The high solubility and excellent photothermal conversion ability demonstrated that polymer IDI particles were promising theranostic agents for treatment of tumors with minor side effects.

Evaluation of PCR primers for detecting the distribution of nitrifiers in mangrove sediments.

Ammonia-oxidizing archaea and ammonia-oxidizing bacteria (AOA and AOB), complete ammonia oxidizers (Comammox), and nitrite-oxidizing bacteria (NOB) play a crucial role in the nitrification process during the nitrogen cycle. However, their occurrence and diversity in mangrove ecosystems are still not fully understood. Here, a total of 11 pairs of PCR primers were evaluated to study the distribution and abundances of these nitrifiers in rhizosphere and non-rhizosphere sediments of a mangrove ecosystem. The amplification efficiency of these 11 pairs of primers was first evaluated and their performances were found to vary considerably. The CamoA-19F/CamoA-616R primer pair was suitable for the amplification of AOA in mangrove sediments, especially on the surface of rhizosphere sediments. Primer pair amoA1F/amoA2R was better for the characterization of novel AOB in the bacterial community of non-rhizosphere sediments of mangroves. In contrast, primer nxrB169F/nxrB638R showed a low abundance of NOB in mangrove sediments (except for R1). Comammox bacteria were abundant and diverse in mangrove sediments, as indicated by both the amoB gene for Comammox clade A and the amoA gene for Comammox Nitrospira clade B. However, the amoA gene for Comammox Nitrospira clade A was not successful in detecting them in the mangrove sediments. Furthermore, 568 operational taxonomic units (OTUs) were obtained by generating a clone library and a high abundance of OTUs was correlated with ammonium, pH, NO2-, and NO3-. Comammox and Comammox Nitrospira were identified by phylogenetic tree analysis, indicating that mangrove sediments harbor newly discovered nitrifiers. Additionally, many AOA and NOB were mainly distributed in the surface layer of the rhizosphere, whereas AOB and Comammox Nitrospira were in the subsurface of non-rhizosphere, as determined by qPCR analysis. Collectively, our findings highlight the limitations of some primers for the identification of specific nitrifying bacteria. Therefore, primers must be carefully selected to gain accurate insights into the ecological distribution of nitrifiers in mangroves. KEY POINTS: • Several sets of PCR primers perform well for the detection of nitrifiers in mangroves. • Mangroves are an important source of newly discovered nitrifiers. • Ammonium, pH, NO2-, and NO3- are important shapers of nitrifier communities in mangroves.

Transformation of HBCDs by Rhodococcus sp. stu-38.

1,2,5,6,9,10-Hexabromocyclododecanes (HBCDs) are brominated flame retardants causing serious environmental pollution. HBCDs in the environment could be transformed to various products. Identification of transformation products has been performed using various mass-spectrometric techniques. However, bacterial transformation of HBCDs yielding low-level products was not well studied. In this paper, a Rhodococcus strain stu-38 which could stereoselectively transform HBCDs in mineral salt medium, seawater, and growth medium was isolated. Seven potential biotransformation products of HBCDs were identified by using GC-MS. These products, including brominated alkenes, dibromocyclododecadiene and bromocyclododecatriene; brominated alkenols, bromocyclododecadienol and bromocyclododecatrienol; fully debrominated compounds, cyclododecadiendiol, 1,2-epoxy-5,9-cyclododecadiene, and cyclododecadienol, were presented in rather low level which could lead to false negative results. The low-level transformation products should not be ignored because their toxicity was less assessment. This research highlighted identification of the low-level transformation products to reveal the complicated stereoselective biotransformation of HBCDs.

Addition of terlipressin to norepinephrine in septic shock and effect of renal perfusion: a pilot study.

PURPOSE: Terlipressin improves renal function in patients with septic shock. However, the mechanism remains unclear. Here, we aimed to evaluate the effects of terlipressin on renal perfusion in patients with septic shock. MATERIALS AND METHODS: This pilot study enrolled patients with septic shock in the intensive care unit of the tertiary hospital from September 2019 to May 2020. We randomly assigned patients to terlipressin and usual care groups using a 1:1 ratio. Terlipressin was intravenously pumped at a rate of 1.3 µg/kg/hour for 24 h. We monitored renal perfusion using renal contrast-enhanced ultrasound (CEUS). The primary outcome was peak sonographic signal intensity (a renal perfusion parameter monitored by CEUS) at 24 h after enrollment. RESULTS: 22 patients were enrolled in this study with 10 in the terlipressin group and 12 in the usual care group. The baseline characteristics of patients between the two groups were comparable. The peak sonographic signal intensity at 24 h after enrollment in the terlipressin group (60.5 ± 8.6 dB) was significantly higher than that in the usual care group (52.4 ± 7.0 dB; mean difference, 7.1 dB; 95% CI, 0.4-13.9; adjusted p = .04). Patients in the terlipressin group had a lower time to peak, heart rates, norepinephrine dose, and a higher stroke volume at 24 h after enrollment. No significant difference in the urine output within 24 h and incidence of acute kidney injury within 28 days was found between the two groups. CONCLUSIONS: Terlipressin improves renal perfusion, increases stroke volume, and decreases norepinephrine dose and heart rates in patients with septic shock.

The NAC Transcription Factors OsNAC20 and OsNAC26 Regulate Starch and Storage Protein Synthesis.

Starch and storage proteins determine the weight and quality of cereal grains. Synthesis of these two grain components has been comprehensively investigated, but the transcription factors responsible for their regulation remain largely unknown. In this study, we investigated the roles of NAM, ATAF, and CUC (NAC) transcription factors, OsNAC20, and OsNAC26 in starch and storage protein synthesis in rice (Oryza sativa) endosperm. OsNAC20 and OsNAC26 showed high levels of amino acid sequence similarity. Both were localized in the aleurone layer, starchy endosperm, and embryo. Mutation of OsNAC20 or OsNAC26 alone had no effect on the grain, while the osnac20/26 double mutant had significantly decreased starch and storage protein content. OsNAC20 and OsNAC26 alone could directly transactivate the expression of starch synthaseI (SSI), pullulanase (Pul), glutelin A1 (GluA1), glutelin B4/5 (GluB4/5), α-globulin, and 16 kD prolamin and indirectly influenced plastidial disproportionating enzyme1 (DPE1) expression to regulate starch and storage protein synthesis. Although they could also bind to the promoters of ADP-Glc pyrophosphorylase small subunit 2b (AGPS2b), ADP-Glc pyrophosphorylase large subunit 2 (AGPL2), and starch branching enzymeI (SBEI), and the expression of the three genes was largely decreased in the osnac20/26 mutant, ADP-Glc pyrophosphorylase and starch branching enzyme activities were unchanged in this double mutant. In addition, OsNAC20 and OsNAC26 are main regulators of Pul, GluB4, α-globulin, and 16 kD prolamin In conclusion, OsNAC20 and OsNAC26 play an essential and redundant role in the regulation of starch and storage protein synthesis.

Real-time ultrasound-guided internal jugular vein cannulation by oblique-axis in-plane: Practice at the Fourth Hospital of Hebei Medical University.

OBJECTIVE: We aimed to evaluate oblique-axis in-plane (OA-IP) techniques for real-time ultrasound-guided internal jugular vein (IJV) cannulation. METHODS: We retrospectively analysed 1065 patients who underwent ultrasound (US)-guided IJV cannulation. We recorded demographic characteristics of patients, success rate, access time, cannulation time, number of attempts and the incidence of acute complications. RESULTS: The overall success rate of the procedure was 100% (n = 1605). In total, 1594 cases (99.3%) were successful at the first attempt, and 11 (0.7%) were successful at the second attempt; no patient required three or more attempts. The mean access time was 18.7 ± 19.3 seconds. The mean cannulation time was 349.0 ± 103.8 seconds. There were 54 (3.4%) acute complications out of the total 1605 cannulations: 23 cases of puncture site bleeding (1.4%), 20 cases allergic to dressing (1.3%), 10 cases of local cervical hematomas (0.6%), and one catheter misplacement (0.1%). There were no major complications 12 hours following the procedure. CONCLUSIONS: The results of our study suggest that OA-IP techniques can improve ultrasound-guided IJV cannulation with a high success rate and safety in clinical practice. Clinicians should consider adopting these methods.

Aerobic and Anaerobic Bacterial and Fungal Degradation of Pyrene: Mechanism Pathway Including Biochemical Reaction and Catabolic Genes.

Microbial biodegradation is one of the acceptable technologies to remediate and control the pollution by polycyclic aromatic hydrocarbon (PAH). Several bacteria, fungi, and cyanobacteria strains have been isolated and used for bioremediation purpose. This review paper is intended to provide key information on the various steps and actors involved in the bacterial and fungal aerobic and anaerobic degradation of pyrene, a high molecular weight PAH, including catabolic genes and enzymes, in order to expand our understanding on pyrene degradation. The aerobic degradation pathway by Mycobacterium vanbaalenii PRY-1 and Mycobactetrium sp. KMS and the anaerobic one, by the facultative bacteria anaerobe Pseudomonas sp. JP1 and Klebsiella sp. LZ6 are reviewed and presented, to describe the complete and integrated degradation mechanism pathway of pyrene. The different microbial strains with the ability to degrade pyrene are listed, and the degradation of pyrene by consortium is also discussed. The future studies on the anaerobic degradation of pyrene would be a great initiative to understand and address the degradation mechanism pathway, since, although some strains are identified to degrade pyrene in reduced or total absence of oxygen, the degradation pathway of more than 90% remains unclear and incomplete. Additionally, the present review recommends the use of the combination of various strains of anaerobic fungi and a fungi consortium and anaerobic bacteria to achieve maximum efficiency of the pyrene biodegradation mechanism.

Diagnostic value of serum soluble triggering expressed receptor on myeloid cells 1 (sTREM-1) in suspected sepsis: a meta-analysis.

BACKGROUND: We aim to synthesize the up-to-date studies to investigate the diagnostic value of serum soluble triggering expressed receptor on myeloid cells 1 (sTREM-1) in suspected sepsis. RESULTS: A total of 19 studies with 2418 patients were finally enrolled in the meta-analysis. The pooled sensitivity was 0.82 (95% CI 0.73 to 0.89), specificity 0.81 (95% CI 0.75 to 0.86), positive likelihood ratio 4.3 (95% CI 3.02 to 6.12), negative likelihood ratio 0.22 (95% CI 0.24 to 0.35), diagnostic odds ratio 20 (95% CI 9 to 41) and AuROC 0.88 (95% CI 0.85 to 0.91). The meta-regression analysis revealed that the sample size, reference standard description, prevalence of sepsis in the trials and consecution of patient recruitment might be the source of heterogeneity. CONCLUSIONS: The serum sTREM-1 had a moderate ability in diagnosis in suspected sepsis based on the current studies. However, more large-scale studies were needed to further evaluate the diagnostic accuracy of sTREM-1.

Mesenchymal stem cells activate Notch signaling to induce regulatory dendritic cells in LPS-induced acute lung injury.

BACKGROUND: Mesenchymal stem cells (MSCs) have been shown to alleviate acute lung injury (ALI) and induce the production of regulatory dendritic cells (DCregs), but the potential link between these two cell types remains unclear. The goal of this study was to investigate the effect and mechanism of MSC-induced regulatory dendritic cells in ALI mice. MATERIAL/METHODS: In vivo experiments, C57BL/6 wild-type male mice were sacrificed at different times after intratracheal injection of LPS to observe changes in lung DC maturation and pathological damage. MSCs, DCregs or/and carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled DCs were administered to the mice by tail vein, and flow cytometry was performed to measure the phenotype of lung DCs and T cells. Lung injury was estimated by the lung wet weight/body weight ratio and histopathological analysis. In vitro, Western blotting or flow cytometry was used to detect the expression of Notch ligand or receptor in MSCs or DCs after coculture or LPS stimulation. Finally, in vivo and in vitro, we used the Notch signaling inhibitor DAPT to verify the effect of the Notch pathway on MSC-induced DCregs and their pulmonary protection. RESULTS: We showed significant accumulation and maturation of lung DCs 2 h after intratracheal injection of LPS, which were positively correlated with the lung pathological injury score. MSC treatment alleviated ALI lung injury, accompanied by a decrease in the number and maturity of classical DCs in the lungs. CFSE-labeled DCs migrated to the lungs of ALI mice more than those of the normal group, and the elimination of CFSE-labeled DCs in the blood was slower. MSCs inhibited the migration of CFSE-labeled DCs to the lung and promoted their elimination in the blood. DCregs, which are obtained by contact coculture of mDCs with MSCs, expressed reduced levels of MHCII, CD86, CD40 and increased levels of PD-L1, and had a reduced ability to stimulate lymphocyte proliferation and activation (expression of CD44 and CD69). mDCs expressing Notch2 significantly increased after coculture with MSCs or rhJagged1, and MSCs expressed more Jagged1 after LPS stimulation. After stimulation of mDCs with recombinant Jagged1, DCs with low expression of MHCII, CD86 and CD40 were also induced, and the effects of both rhJagged1 and MSCs on DCs were blocked by the Notch inhibitor DAPT. Intra-airway DAPT reversed the inhibitory effect of mesenchymal stem cells on DC recruitment to the lungs and its maturation. CONCLUSIONS: Our results suggested that the recruitment and maturation of lung DCs is an important process in early ALI, MSCs attenuate LPS-induced ALI by inducing the production of DCregs by activating Notch signaling.

Plasma Midkine Is Associated With 28-Day Mortality and Organ Function in Sepsis.

BACKGROUND: Midkine has been reported to play a crucial role in inflammatory, hypoxia, and tissue injury processes. We aimed to investigate plasma midkine in septic patients and its association with 28-day mortality and organ function. METHODS: Septic patients admitted to the Department of Critical Care Medicine, Zhongda Hospital, a tertiary hospital, from November 2017 to March 2018 were enrolled in the study. The baseline characteristics of the septic patients were recorded at admission. A peripheral blood sample was obtained at admission, and plasma midkine levels were evaluated with an immunoassay. All patients were followed up with for 28 days, with all-cause mortality being recorded. RESULTS: A total of 26 septic patients were enrolled, which included 18 survivors and 8 nonsurvivors at day 28. Plasma midkine levels were significantly elevated in the nonsurvivor group compared with the survivors (ng/L, 763.6 [404.7-1305], 268.5 [147.8-511.4]; P = .0387]. Plasma midkine levels were elevated in septic patients with moderate/severe acute respiratory distress syndrome (ARDS) compared with patients with non/mild ARDS (ng/L, 522.3 [336.6-960.1] vs 243.8 [110.3-478.9]; P = .0135) and in those with acute kidney injury compared with those without (ng/L, 489.8 [259.2-1058] vs 427.9 [129.6-510.3]; P = .0973). Changes in plasma midkine levels were also associated with extravascular lung water index (P = .063) and pulmonary vascular permeability index (P = .049). CONCLUSIONS: Plasma midkine was associated with 28-day mortality, as well as pulmonary and kidney injury, in septic patients.

The Effect of High-Flow Nasal Oxygen Therapy on Postoperative Pulmonary Complications and Hospital Length of Stay in Postoperative Patients: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the effect of high-flow nasal cannula oxygen (HFNO) therapy on hospital length of stay (LOS) and postoperative pulmonary complications (PPCs) in adult postoperative patients. DATA SOURCES: PubMed, Embase, the Cochrane Library, Web of Science of Studies, China National Knowledge Index, and Wan Fang databases were searched until July 2018. STUDY SELECTION: Randomized controlled trials (RCTs) comparing HFNO with conventional oxygen therapy or noninvasive mechanical ventilation in adult postoperative patients were included. The primary outcomes were hospital LOS and PPCs; short-term mortality (defined as intensive care unit, hospital, or 28-day mortality) and intubation rate were the secondary outcomes. DATA EXTRACTION: Demographic variables, high-flow oxygen therapy application, effects, and side effects were retrieved. Data were analyzed by the methods recommended by the Cochrane Collaboration. The strength of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation. Random errors were evaluated with trial sequential analysis. DATA SYNTHESIS: Fourteen studies (2568 patients) met the inclusion criteria and were included. Compared to the control group, the pooled effect showed that HFNO was significantly associated with a shorter hospital stay (mean difference: -0.81; 95% confidence interval [CI]: -1.34 to -0.29, P = .002), but not mortality (risk ratio [RR]: 1.0, 95% CI: 0.63 to 1.59, P = 1.0). Weak evidence of a reduction in reintubation rate (RR: 0.76, 95% CI: 0.57-1.01, P = .06) and PPC rate (RR: 0.89, 95% CI: 0.75-1.06, P = .18) with HFNO versus control group was recorded. CONCLUSIONS: The available RCTs suggest that, among the adult postoperative patients, HFNO therapy compared to the control group significantly reduces hospital LOS.

mTOR/STAT-3 pathway mediates mesenchymal stem cell-secreted hepatocyte growth factor protective effects against lipopolysaccharide-induced vascular endothelial barrier dysfunction and apoptosis.

Mesenchymal stem cells (MSCs) protect the endothelial barrier complex and survival, implicated in the pathogenesis of acute lung injury (ALI) via paracrine hepatocyte growth factor (HGF). However, the mechanism of HGF in endothelial regulation remains unclear. Here, we introduced a coculture protocol of pulmonary microvascular endothelial cells (PMVECs) and overexpression of the HGF gene of MSCs (MSC-HGF). Immunofluorescence and endothelial permeability analysis revealed that MSC-HGF protected endothelial tight junction protein occludin expression and attenuated cellular permeability as well as endothelial apoptosis. To investigate the novel mechanism mammalian TOR (mTOR)/ signal transducer and activator of transcription 3 (STAT-3) signaling in HGF protective effects against endothelial barrier and apoptosis, we used recombinant mouse HGF in endothelial cells. In addition, we used mTOR inhibitor rapamycin to inhibit the mTOR pathway. Our study demonstrated that rapamycin decreased the protective effects of HGF on the endothelium by decreasing tight junction protein occludin expression and cell proliferation, and raising lipopolysaccharide (LPS)-induced endothelial permeability, endothelial cell injury factors ET-1 and vWF. Similarly, the protective effects of HGF on reducing endothelial barrier and apoptosis were weakened when PMVECs were treated with the STAT-3 inhibitor S3I-201. Moreover, mTOR/STAT-3 were activated by HGF demonstrated as raising mTOR (Ser2448) and STAT3 (Ser727) phosphorylation proteins, leading to endothelial barrier improvement and survival. Reversely, rapamycin or S3I-201 inhibited mTOR/STAT-3 activation. Taken together, our findings highlight that the activation of the mTOR/STAT-3 pathway provides novel mechanistic insights into MSC-secreted HGF protection against LPS-induced vascular endothelial permeability dysfunction and apoptosis, which contributes to decreasing microvascular loss and lung injury.

Effect of surfactant administration on outcomes of adult patients in acute respiratory distress syndrome: a meta-analysis of randomized controlled trials.

INTRODUCTION: Surfactant is usually deficiency in adult acute respiratory distress syndrome(ARDS) patients and surfactant administration may be a useful therapy. The aim of this study was to perform a meta-analysis of the effect of surfactant administration on outcomes of adult patients with acute respiratory distress syndrome. METHODS: PubMed, EMBASE, Medline, Cochrane database, Elsevier, Web of Science and http://clinicaltrials.gov were searched and investigated until December 2017. Randomized controlled trials(RCTs) comparing surfactant administration with general therapy in adult patients with ARDS were enrolled. The primary outcome was mortality (7-10-day, 28-30-day and 90-180-day). Secondary outcome included oxygenation (PaO2/FiO2 ratio). Demographic variables, surfactant administration, and outcomes were retrieved. Sensitivity analyses were used to evaluate the impact of study quality issues on the overall effect. Funnel plot inspection, Egger's and Begger's test were applied to investigate the publication bias. Internal validity was assessed with the risk of bias tool. Random errors were evaluated with trial sequential analysis(TSA). Quality levels were assessed by Grading of Recommendations Assessment, Development, and Evaluation methodology(GRADE). RESULTS: Eleven RCTs with 3038 patients were identified. Surfactant administration could not improve mortality of adult patients [Risk ratio (RR) (95%CI)) = 1.02(0.93-1.12), p = 0.65]. Subgroup analysis revealed no difference of 7-10-day mortality [RR(95%CI)) = 0.89(0.54-1.49), p = 0.66], 28-30-day mortality[RR(95%CI) = 1.00(0.89-1.12), p = 0.98] and 90-180-day mortality [RR(95%CI) = 1.11(0.94-1.32), p = 0.22] between surfactant group and control group. The change of the PaO2/FiO2 ratio in adult ARDS patients had no difference [MD(95%CI) = 0.06(- 0.12-0.24), p = 0.5] after surfactant administration. Finally, TSA and GRADE indicated lack of firm evidence for a beneficial effect. CONCLUSIONS: Surfactant administration has not been shown to improve mortality and improve oxygenation for adult ARDS patients. Large rigorous randomized trials are needed to explore the effect of surfactant to adult ARDS patients.

Cognitive and neuroimaging changes in healthy immigrants upon relocation to a high altitude: A panel study.

BACKGROUND: Cognitive and neuroimaging changes under chronic high-altitude exposure have never been followed up and dynamically assessed. OBJECTIVES: To investigate the cognitive and brain structural/functional alterations associated with chronic high-altitude exposure. METHODS: Sixty-nine college freshmen that were immigrating to Tibet were enrolled and followed up for two years. Neuropsychological tests, including verbal/visual memory and simple/recognition reaction time, were utilized to determine whether the subjects' cognitive function had changed in response to chronic high-altitude exposure. Structural magnetic resonance imaging (MRI) and resting-state functional MRI (rs-fMRI) were used to quantify brain gray matter (GM) volumes, regional homogeneity (ReHo) and functional connectivity (FC) alterations before and after exposure. Areas with changes in both GM and ReHo were used as seeds in the inter-regional FC analysis. RESULTS: The subjects showed significantly lower accuracy in memory tests and longer reaction times after exposure, and neuroimaging analysis showed markedly decreased GM volumes and ReHo in the left putamen. FC analysis seeding of the left putamen showed significantly weakened FC with the superior temporal gyrus, anterior/middle cingulate gyrus and other brain regions. In addition, decreased ReHo was found in the superior temporal gyrus, superior parietal lobule, anterior cingulate gyrus and medial frontal gyrus, while increased ReHo was found in the hippocampus. Differences in ReHo/FC before and after high-altitude exposure in multiple regions were significantly correlated with the cognitive changes. CONCLUSION: Cognitive functions such as working memory and psychomotor function are impaired during chronic high-altitude exposure. The putamen may play an important role in chronic hypoxia-induced cognitive impairment. Hum Brain Mapp 38:3865-3877, 2017. © 2017 Wiley Periodicals, Inc.

Comparative analysis of the transcriptome of the overwintering desert beetle Microdera punctipennis.

The cold tolerance mechanisms of insect have been studied extensively on the model species Drosophila and a few other species at the transcriptional level. However studies on insects that inherit strong cold tolerance are limited. Cold hardy Tenebrionid beetle Microdera punctipennis is endemic to Gurbantonggut Desert, northwest of China. However, its genomic information is lacking. To investigate the overwintering mechanisms of M. punctipennis adult, RNA-seq was performed on the winter adults and the control adults that were kept in laboratory at 30 °C. A total of 175,247 unigenes were acquired with an average length of 645 bp. By using DESeq package, we identified 3367 unigenes that were up-regulated and 7988 down-regulated in the winter adults compared with the controls. To further our understanding of these differentially expressed genes (DEGs), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Pathway analysis showed that the "ECM-receptor interaction", "PI3K-Akt signaling pathway", "Estrogen signaling pathway", "Tight junction", and "Regulation of actin cytoskeleton", etc. might play important roles in M. punctipennis overwintering. The DEGs results from the RNA-Seq were confirmed partially by qRT-PCR for 13 DEGs, which showed high consistence with a Pearson's correlation coefficient of 0.851. Overall, the sequence data will provide basic information for subsequent bioinformatical analysis and mining of the genes responsible for cold tolerance in M. punctipennis, as well as for understanding the molecular mechanisms of desert beetle overwintering.

Maternal allergic disease history affects childhood allergy development through impairment of neonatal regulatory T-cells.

BACKGROUND: Maternal allergic disease history and impaired regulatory T-cells (Tregs) are critical risk factors for allergy development in children. However, the mechanisms that underlie these risk factors remain poorly defined. Therefore, the aim of this study was to assess whether maternal allergies affect the Tregs of offspring and lead to allergy development in childhood. METHODS: A total of 332 mothers of healthy newborns (234 from no allergic mothers, 98 from allergic mothers) were recruited to this study. Detailed questionnaires were administered yearly to determine the allergy status of the mothers and the newborns from birth to 3 years of age. Cord blood samples obtained at the time of birth were analysed for Treg counts, as well Treg activity, based on their response to Toll-like receptor (TLR) stimuli such as lipid A (LPA) and peptidoglycans (PPG). Surface markers, associated genes, suppressive capacity, and cytokine levels of Tregs were also measured. Possible correlations between Treg activity and maternal or neonate allergies were assessed. In addition, environmental microbial content and other known risk factors for allergies were measured. RESULTS: Cord blood mononuclear cells (CBMCs) from offspring with allergic mothers showed fewer CD4(+)CD25(+)FOXP3(+) T cells, lower expression levels of associated genes, and reduced cytokine production of interleukin (IL)-10 and interferon-γ (P < 0.05), especially via the PPG-TLR2 pathway. Suppression of effector T cells by Tregs from children of mothers with allergies was impaired, especially IL-13 production by Type 2 T helper (Th2) cells (P = 0.026). Children who developed allergies in the first 3 years of life had lower numbers of CD4(+)CD25(+)FOXP3(+) T cells and reduced FOXP3 expression and IL-10 production as newborns (P < 0.05). Maternal allergic background was identified as a risk factor for allergy development in the children (Odds ratio (OR) = 2.46, 95 % CI = 1.05-5.79); while declining Treg numbers, IL-10 production, and FOXP3 expression in neonates (PPG and LPA stimulated) were identified as independent risk factors for allergic diseases in offspring at 3 years of age after adjusting for maternal allergic history and environmental factors (P < 0.05). CONCLUSION: Maternal allergy correlated with impaired Tregs in neonates, and this could enhance the susceptibility of offspring to allergic diseases in early childhood due to an imbalance of Th1 and Th2 cells.

Solvent-Induced Single Crystal-Single Crystal Transformation of an Interpenetrated Three-Dimensional Copper Triazole Catalytic Framework.

The 2-fold interpenetrated 3D framework 1 can be solvent-induced to noninterpenetrated framework 1' in a reversible single crystal-single crystal transformation fashion. In addition, 1' represents the first catalyst based on triazole to catalyze the aerobic homocoupling of various substituted arylboronic acids.