Neurometabolite levels in the brains of patients with autism spectrum disorders: A meta-analysis of proton magnetic resonance spectroscopy studies (N = 1501).

Evidence suggests that neurometabolite alterations may be involved in the pathophysiology of autism spectrum disorders (ASDs). We performed a meta-analysis of proton magnetic resonance spectroscopy (1H-MRS) studies to examine the neurometabolite levels in the brains of patients with ASD. A systematic search of PubMed and Web of Science identified 54 studies for the meta-analysis. A random-effects meta-analysis demonstrated that compared with the healthy controls, patients with ASD had lower N-acetyl-aspartate-containing compound (NAA) and choline-containing compound (Cho) levels and NAA/(creatine-containing compound) Cr ratios in the gray matter and lower NAA and glutamate + glutamine (Glx) levels in the white matter. Furthermore, NAA and gamma-aminobutyric acid (GABA) levels, NAA/Cr ratios, and GABA/Cr ratios were significantly decreased in the frontal cortex of patients with ASD, whereas glutamate (Glu) levels were increased in the prefrontal cortex. Additionally, low NAA levels and GABA/Cr ratios in the temporal cortex, low NAA levels and NAA/Cr ratios in the parietal and dorsolateral prefrontal cortices, and low NAA levels in the cerebellum and occipital cortex were observed in patients with ASD. Meta-regression analysis revealed that age was positively associated with effect size in studies analyzing the levels of gray matter NAA and white matter Glx. Taken together, these results provide strong clinical evidence that neurometabolite alterations in specific brain regions are associated with ASD and age is a confounding factor for certain neurometabolite levels in patients with ASD.

Polymorphisms of the Vitamin D Receptor Gene and Sex-Differential Associations with Lipid Profiles in Chinese Han Adults / 生物医学与环境科学（英文）

OBJECTIVE@#To explore the association of single nucleotide polymorphisms (SNPs) of the vitamin D receptor gene ( VDR) with circulating lipids considering gender differences.@*METHODS@#Of the Han Chinese adults recruited from a health examination center for inclusion in the study, the circulating lipids, 25-hydroxyvitamin D (25OHD), and other parameters were measured. The VDR SNPs of Cdx2 (rs11568820), Fok1 (rs2228570), Apa1 (rs7975232), and Taq1 (rs731236) were genotyped with a qPCR test using blood DNA samples, and their associations with lipids were analyzed using logistic regression.@*RESULTS@#In the female participants ( n = 236 with dyslipidemia and 888 without dyslipidemia), multiple genotype models of Fok1 indicated a positive correlation of B (not A) alleles with LDLC level ( P < 0.05). In the male participants ( n = 299 with dyslipidemia and 564 without dyslipidemia), the recessive model of Cdx2 and the additive and recessive models of Fok1 differed ( P < 0.05) between the HDLC-classified subgroups, respectively, and Fok1 BB and Cdx2 TT presented interactions with 25OHD in the negative associations with HDLC ( P < 0.05).@*CONCLUSION@#In the Chinese Han adults included in the study, the Fok1 B-allele of VDR was associated with higher LDLC in females, and the Fok1 B-allele and the Cdx2 T-allele of VDR were associated with lower HDLC in males. The interaction of VD and Fok1 BB or Cdx2 TT in males synergistically decreased HDLC levels.

Interaction of olfaction and feeding behavior and its neural mechanism / 生理学报

Olfaction and food intake are interrelated and regulated. In the process of feeding, the metabolic signals in the body and the feeding signals produced by food stimulation are first sensed by the arcuate nucleus of hypothalamus and the nucleus tractus solitarius of brain stem, and then these neurons project to the paraventricular nucleus of hypothalamus. The paraventricular nucleus transmits the signals to other brain regions related to feeding and regulates feeding behavior. In this process, olfactory signals can be transmitted to hypothalamus through olfactory bulb and olfactory cortex to regulate feeding behavior. At the same time, gastrointestinal hormones (ghrelin, insulin, leptin, etc.) and some neurotransmitters (acetylcholine, norepinephrine, serotonin, endocannabinoid, etc.) produced in the process of feeding act on the olfactory system to regulate olfactory function, which in turn affects the feeding itself. This review summaries the research progress of the interaction between olfaction and food intake and its internal mechanism from the aspects of neuronal and hormonal regulation.

Total Infectomes Characterization of Respiratory Infections in pre-COVID-19 Wuhan, China

At the end of 2019 Wuhan witnessed an outbreak of "atypical pneumonia" that later developed into a global pandemic. Metagenomic sequencing rapidly revealed the causative agent of this outbreak to be a novel coronavirus - SARS-CoV-2. Herein, to provide a snapshot of the pathogens in pneumonia-associated respiratory samples from Wuhan prior to the emergence of SARS-CoV-2, we collected bronchoalveolar lavage fluid samples from 408 patients presenting with pneumonia and acute respiratory infections at the Central Hospital of Wuhan between 2016 and 2017. Unbiased total RNA sequencing was performed to reveal their "total infectome", including viruses, bacteria and fungi. Consequently, we identified 37 pathogen species, comprising 15 RNA viruses, 3 DNA viruses, 16 bacteria and 3 fungi, often at high abundance and including multiple co-infections (12.8%). However, SARS-CoV-2 was not present. These data depict a stable core infectome comprising common respiratory pathogens such as rhinoviruses and influenza viruses, an atypical respiratory virus (EV-D68), and a single case of a sporadic zoonotic pathogen - Chlamydia psittaci. Samples from patients experiencing respiratory disease on average had higher pathogen abundance than healthy controls. Phylogenetic analyses of individual pathogens revealed multiple origins and global transmission histories, highlighting the connectedness of the Wuhan population. This study provides a comprehensive overview of the pathogens associated with acute respiratory infections and pneumonia, which were more diverse and complex than obtained using targeted PCR or qPCR approaches. These data also suggest that SARS-CoV-2 or closely related viruses were absent from Wuhan in 2016-2017.

COVID-19 severity is associated with immunopathology and multi-organ damage

COVID-19 is characterised by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand how host responses contribute to COVID-19 pathophysiology, we used a multi-omics approach to identify molecular markers in peripheral blood and plasma samples that distinguish COVID-19 patients experiencing a range of disease severities. A large number of expressed genes, proteins, metabolites and extracellular RNAs (exRNAs) were identified that exhibited strong associations with various clinical parameters. Multiple sets of tissue-specific proteins and exRNAs varied significantly in both mild and severe patients, indicative of multi-organ damage. The continuous activation of IFN-I signalling and neutrophils, as well as a high level of inflammatory cytokines, were observed in severe disease patients. In contrast, COVID-19 in mild patients was characterised by robust T cell responses. Finally, we show that some of expressed genes, proteins and exRNAs can be used as biomarkers to predict the clinical outcomes of SARS-CoV-2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID-19 and will help guide future studies in this area.

Complete genome characterisation of a novel coronavirus associated with severe human respiratory disease in Wuhan, China

Emerging and re-emerging infectious diseases, such as SARS, MERS, Zika and highly pathogenic influenza present a major threat to public health1-3. Despite intense research effort, how, when and where novel diseases appear are still the source of considerable uncertainly. A severe respiratory disease was recently reported in the city of Wuhan, Hubei province, China. At the time of writing, at least 62 suspected cases have been reported since the first patient was hospitalized on December 12nd 2019. Epidemiological investigation by the local Center for Disease Control and Prevention (CDC) suggested that the outbreak was associated with a sea food market in Wuhan. We studied seven patients who were workers at the market, and collected bronchoalveolar lavage fluid (BALF) from one patient who exhibited a severe respiratory syndrome including fever, dizziness and cough, and who was admitted to Wuhan Central Hospital on December 26th 2019. Next generation metagenomic RNA sequencing4 identified a novel RNA virus from the family Coronaviridae designed WH-Human-1 coronavirus (WHCV). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that WHCV was most closely related (89.1% nucleotide similarity similarity) to a group of Severe Acute Respiratory Syndrome (SARS)-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) previously sampled from bats in China and that have a history of genomic recombination. This outbreak highlights the ongoing capacity of viral spill-over from animals to cause severe disease in humans.

11-watt single-frequency 1342-nm laser based on multi-segmented Nd:YVO4 crystal.

High power continuous-wave (CW) single-frequency 1342 nm lasers are of interest for fundamental research, particularly, for laser cooling of lithium atoms. Using the popular Nd:YVO4 laser crystal requires careful heat management, because strong thermal effects in the gain medium are the most severe limitations of output power. Here, we present a multi-segmented Nd:YVO4 crystal design that consists of three segments with successive doping concentrations, optimized using a theoretical model. In order to quantify the optimization, we measured the thermal lens power of conventional crystal designs and compare them to our multi-segmented design. The optimized design displays a two times lower thermal lens dioptric power for the same amount of absorbed pump power in the non-lasing case. Using the optimized design, we demonstrate a high power all-solid-state laser emitting 10.0 W single-frequency radiation at 1342 nm when operating the laser crystal at room temperature. Further integration of the laser allows us to operate the laser crystal below room temperature for improving output power up to 11.4 W at 8°C. This is explained by the reduction of energy-transfer upconversion and excited-state absorption effects. Stable free-running operation at the low temperature of 8 °C is achieved with the power stability of ± 0.42 % by peak-to-peak fluctuation and frequency peak-to-peak fluctuation of ± 72 MHz in three hours.

High-power 671 nm laser by second-harmonic generation with 93% efficiency in an external ring cavity.

Second-harmonic generation (SHG) is useful for obtaining single-frequency continuous-wave laser sources at various wavelengths for applications ranging from biology to fundamental physics. Using an external power-enhancement cavity is an effective approach to improve the frequency conversion efficiency. However, thermal effects limit the efficiency, particularly, in high-power operation. Therefore, reducing thermal effects is important when designing a cavity. This Letter reports the use of an external ring cavity for SHG, yielding a 5.2 W, 671 nm laser light with a conversion efficiency of 93.8±0.8% which, to the best of our knowledge, is a new record of conversion efficiency for an external ring cavity. It is achieved using a 10 mm length periodically poled potassium titanyl phosphate crystal and a 65 µm radius beam waist in the cavity so as to minimize thermal dephasing and thermal lensing. Furthermore, a method is developed to determine a conversion efficiency more accurately based on measuring the pump depletion using a photodiode detector and a maximum pump depletion up to 97% is recorded. In this method, the uncertainty is much less than that achieved in a common method by direct measuring with a power meter.

The effect of AHR small interference on hepatoma HCCLM3 cell proliferation in vitro and tumor growth in vivo / 肿瘤

Objective: To investigate the effect of aryl hydrocarbon receptor (AHR) RNA interference on hepatoma HCCLM3 cell proliferation and migration and to explore its possible mechanism. Methods: After HCCLM3 cells transfection with specific AHR-small interference RNA (siRNA), the expression level of AHR mRNA was detected by real-time fluorescence quantitative-PCR, and the expression levels of AHR, stress-activated protein kinases (SAPK)/c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK 1/2) and c-Jun phosphorylation were detected by Western blotting. Then the proliferation and migration of HCCLM3 cells after transfection with AHR-siRNA were detected by cell counting kit-8 (CCK-8) and Transwell assay, respectively. Synthesize AHR gene-specific small hairpin RNA (shRNA) to construct recombinant virus vector pMKO.1/puro-shAHR which stable knockdown AHR, and the recombinant vector was infected into HCCLM3 cells and then implanted into nude mice to construct subcutaneous tumor model. The growth of xenografted tumor in nude mice was examined. The expression levels of AHR protein in HCCLM3 cells and xenografted tumor tissues after infection with pMKO.1/puro-shAHR were detected by Western blotting. Results: The expression levels of AHR mRNA and protein were significantly reduced in HCCLM3 cells transfected with AHR-siRNA (P < 0.01), and the proliferation and migration of HCCLM3 cells were inhibited (P < 0.01). The expression levels of SAPK/JNK, ERK 1/2 and c-Jun phosphorylation were depressed (P < 0.01). The volume and weight of HCCLM3 cells xenografted tumor in nude mice after infection with pMKO.1/puro-shAHR were lower than those of the control group (HCCLM3 cells were infected with pMKO.1/puro-shNC) (P < 0.01). The expression levels of AHR protein in HCCLM3 cells and xenografted tissues after infection with pMKO.1/puro-shAHR were decreased (P < 0.01). Conclusion: AHR may promote HCCLM3 cell proliferation and migration in vitro by up-regulating the phosphorylation levels of ERK1/2, SAPK/JNK and c-Jun. Copyright © 2014 by TUMOR.