AimsThis study aimed to illuminate the neuropathological landscape of attention deficit hyperactivity disorder (ADHD) by a multiscale macro–micro‐molecular perspective from in vivo neuroimaging data.MethodsThe “ADHD‐200 initiative” repository provided multi‐site high‐quality resting‐state functional connectivity (rsfc‐) neuroimaging for ADHD children and matched typically developing (TD) cohort. Diffusion mapping embedding model to derive the functional connectome gradient detecting biologically plausible neural pattern was built, and the multivariate partial least square method to uncover the enrichment of neurotransmitomic, cellular and chromosomal gradient‐transcriptional signatures of AHBA enrichment and meta‐analytic decoding.ResultsCompared to TD, ADHD children presented connectopic cortical gradient perturbations in almost all the cognition‐involved brain macroscale networks (all pBH <0.001), but not in the brain global topology. As an intermediate phenotypic variant, such gradient perturbation was spatially enriched into distributions of GABAA/BZ and 5‐HT2A receptors (all pBH <0.01) and co‐varied with genetic transcriptional expressions (e.g. DYDC2, ATOH7, all pBH <0.01), associated with phenotypic variants in episodic memory and emotional regulations. Enrichment models demonstrated such gradient‐transcriptional variants indicated the risk of both cell‐specific and chromosome‐ dysfunctions, especially in enriched expression of oligodendrocyte precursors and endothelial cells (all pperm <0.05) as well enrichment into chromosome 18, 19 and X (pperm <0.05).ConclusionsOur findings bridged brain macroscale neuropathological patterns to microscale/cellular biological architectures for ADHD children, demonstrating the neurobiologically pathological mechanism of ADHD into the genetic and molecular variants in GABA and 5‐HT systems as well brain‐derived enrichment of specific cellular/chromosomal expressions.

Aims: When entering a mountain plateau, people are at risk of developing acute mountain sickness (AMS), for which there are limited prophylactic medicines available. This study aimed at exploring the effectiveness of ibuprofen, acetazolamide, and methazolamide in preventing AMS and at providing valuable insights for the future development of related drugs.Methods: A total of 137 mountaineers were recruited for this study and divided into six groups: a control group, an ibuprofen group, an acetazolamide group, a methazolamide group, an ibuprofen/methazolamide combination group, and a high‐dose ibuprofen/methazolamide combination group. After the assigned drug was taken for three days at a lower elevation (300 m), the participants ascended to a plateau environment at 5050 m. The Lake Louise AMS Score (LLS) system was used to diagnose and evaluate the AMS rates of the mountaineers in each group, and the results were compared through statistical analysis.Results: The results show that all the medications tested herein were effective in preventing AMS, but their level of effectiveness varied. The prevalence of AMS was 50.00% in the control group, 14.29% in the ibuprofen group, 5.56% in the acetazolamide group, 27.27% in the methazolamide group, 44.8% in the ibuprofen and methazolamide group, and 22.50% in the high‐dose ibuprofen and methazolamide group. Acetazolamide demonstrated a significant prophylactic effect on symptoms related to AMS diagnosis, and ibuprofen showed the best efficacy for preventing headache.Conclusion: Acetazolamide remains an effective medicine for preventing AMS. Ibuprofen combined with methazolamide is less effective than ibuprofen alone to prevent AMS.Trial Registration: ClinicalTrials.gov identifier: ChiCTR-TRC-12002219

Beauveria bassiana, a well-known filamentous biocontrol fungus, is the main pathogen of numerous field and forest pests. To explore the potential factors involved in the fungal pathogenicity, Bbhox2, an important and conserved functional transcription factor containing homeodomain was carried out by functional analysis. Homologous recombination was used to disrupt the Bbhox2 gene in B.bassiana. The conidia yield of the deletant fungal strain was significantly reduced. The conidial germination was faster, and stress tolerance to Congo red and high osmotic agents were decreased compared with that in the wildtype. Additionally, ΔBbhox2 showed a dramatic reduction in virulence no matter in topical inoculations or in intra-hemolymph injections against Galleria mellonella larvae, which is likely due to the failure of appressorium formation and the defect in producing hyphal body. These results indicate that the Bbhox2 gene markedly contributes to conidiation and pathogenicity in B. bassiana.

Objective: To compare the ability of the Chinese AMS Score (CAS) to detect acute mountain sickness (AMS) using the 2018 version of the Lake Louise Score (LLS) as reference. Methods: After flying from Chengdu (altitude: 500 m) to Lhasa (3,658 m), 2,486 young men completed a questionnaire. The questionnaire contained LLS and CAS items. An LLS >= 3 and/or a CAS >= cutoff were used as the criteria for AMS. Hierarchical cluster analysis and two-step cluster analysis were used to investigate relationships between the symptoms. Results: AMS incidence rates were 33.8% (n = 840) with the LLS and 59.3% (n = 1,473) with the CAS (chi(2) = 872.5, p < 0.001). The LLS and CAS had a linear relationship (orthogonal regression, Pearson r = 0.91, p < 0.001). With the LLS as the standard, the CAS had high diagnostic accuracy (area under the curve = 0.95, 95% confidence interval: 0.94-0.96). However, with the CAS, 25.5% (n = 633) more participants were labeled as having AMS than with the LLS (false positives). Two clusters were identified: one with headache only (419 participants, 66.2%) and one without headache but with other symptoms (214 participants, 33.8%). Reducing the weight of headache in the CAS allowed to align CAS and LLS. Conclusion: In comparison to the LLS, the CAS has a sensitivity close to 100% but lacks specificity given the high rate of false positives. The different weight of headaches may be the main reason for the discrepancy.

Objective To explore the role and mechanism of DNase 2α on hypoxia-induced proliferation of rat pulmonary artery smooth muscle cells (RPASMCs). Methods Primary RPASMCs were cultured with 3%O2 to establish a hypoxia-induced cell proliferation model. Small interference RNA (siRNA) was used to decrease the expression of Dnase2a, and corresponding plasmids were employed to up-regulate the expression of Dnase2a and Hif1a. Cell proliferation was induced by exogenous mitochondrial DNA (mtDNA). Proline hydroxylase inhibitor ROXA was adopted to enhance the expression of HIF-1α. The proliferation of cells in each group was detected by MTS assay, the mRNA level of Dnase2a was detected by qPCR, and the protein levels of DNase 2α, proliferating cell nuclear antigen (PCNA) and cell cycle protein D1 (Cyclin D1) were detected by Western blotting. Results Hypoxia induced the proliferation of RPASMCs and up-regulated the expression of DNase 2α. siRNA significantly decreased the expression of Dnase2a (P < 0.05) and promoted the hypoxia-induced proliferation of RPASMCs (P < 0.05), and the protein expression of PCNA and Cyclin D1 was up-regulated (P < 0.05). Overexpression of Dnase2a up-regulated the expression of Dnase2a (P < 0.05) and inhibited the proliferation of RPASMCs induced by hypoxia (P < 0.05). Exogenous mtDNA also promoted the proliferation of RPASMCs, while, overexpression of DNase 2α inhibited the above proliferation (P < 0.05). Overexpression of Hif1a or proline hydroxylase inhibitor ROXA could significantly up-regulate the protein expression of HIF-1α and DNase 2α (P < 0.05). Conclusion DNase 2α inhibits the proliferation of RPASMCs induced by hypoxia or mtDNA, whose expression induced by hypoxia is associated with HIF-1α.

INTRODUCTION:Inadequate oxygen availability may lead to impairment of neurocognitive functions. The aim of the present study was to investigate the effect of acute high-altitude exposure on the cerebral hemodynamic response and working memory.METHODS:The same subjects performed working memory exercises with forward and backward digit span tasks both under normal oxygen conditions and in large simulated hypobaric hypoxia chambers, and a series of physiological parameters were evaluated. Functional near-infrared spectroscopy was used to measure cerebral blood flow changes in the dorsolateral prefrontal cortex (DLPFC) during the tasks.RESULTS:Compared with normoxic conditions, under hypoxic conditions, the heart rate and blood pressure increased, blood oxygen saturation decreased significantly, and the forward task had similar accuracy and response time, while the backward task had lower accuracy and longer response time. Neuroimaging analysis showed increased activation in the DLPFC during the forward task and deactivation during the backward task under hypobaric hypoxia conditions.CONCLUSION:Acute high-altitude exposure leads to physiological adaptations. The abnormal hemodynamic responses of the DLPFC to hypoxia at low pressure reveal the disruption of neurocognitive function by acute high-altitude exposure, which compromises complex cognitive functions, and provides a promising application for functional near infrared spectroscopy in the exploration of neural mechanisms in the brain during high-altitude exposure.

Beauveria bassiana is an important entomopathogenic fungus used to control a variety of insect pests. Conidia are the infective propagules of the fungus. However, some important factors that influence conidiation are still to be investigated. In this study, a mutant with decreased conidial production and hyphal growth was identified from a random T-DNA insertional library of B. bassiana. The corresponding gene (Bbthi) for this mutation encodes a putative thiazole synthase. Thiazole and pyrimidine are structural components of thiamine (vitamin B1), which is an essential nutrient for all forms of life. Disruption of Bbthi, Bbpyr, a putative pyrimidine synthetic gene, or both in B. bassiana results in a significant decrease of thiamine content. Loss of Bbthi and Bbpyr function significantly decreased the conidial production and hyphal growth, as well as disrupted the integrity of conidial cell wall. However, the defect of Bbpyr and Bbthi does not decrease the virulence of B. bassiana. Our results indicate the importance of thiamine biosynthesis in conidiation of B. bassiana, and provide useful information to produce conidia of entomopathogenic fungi for biocontrol of insect pests.