Noninvasive ultrasound deep brain stimulation of nucleus accumbens induces behavioral avoidance

Ultrasound stimulation is an emerging noninvasive option in treating neuropsychiatric disorders. The present study investigates the behavioral alterations resulting from ultrasound stimulation on the nucleus accumbens(NAc) in freely moving mice. Our results show that an acute ultrasound stimulation on the NAc, rather than the visual cortex or auditory cortex, led to a pronounced avoidance behavior, while repeated NAc ultrasound stimulation resulted in an obvious conditioned place aversion with changes in synaptic protein(Glu A1/2 subunit) expression. Notably, NAc ultrasound stimulation suppressed the morphine-induced conditioned place preference. The results provide evidence that NAc ultrasound stimulation can be applied as a potential noninvasive therapeutic option in treating psychiatric disorders.     

Long-term changes in Noctiluca scintillans blooms along the Chinese coast from 1933 to 2020

Noctiluca scintillans is one of the most common harmful algal species and widely known due to its bioluminescence. In this study, the spatial distribution, seasonal variations, and long-term trends of N. scintillans blooms in China and the related drivers were analyzed and discussed. From 1933 to 2020, a total of 265 events of N. scintillans blooms were recorded in Chinese coastal waters, with a total duration of 1052 days. The first N. scintillans bloom occurred in Zhejiang in 1933, and only three events were recorded before 1980. From 1981 to 2020, N. scintillans caused harmful algal blooms (HABs) almost every year, both the average duration and the proportion of multiphase HABs showed an increasing trend. 1986–1992, 2002–2004, and 2009–2016 were the three peak periods with a frequency of no less than five events of N. scintillans blooms per year. In terms of spatial distribution, N. scintillans blooms spread from the Southeast China Sea to the Bohai Sea after 2000, Guangdong, Fujian, and Hebei were the three provinces with the highest numbers of recorded events of N. scintillans blooms. Moreover, 86.8% of the events of N. scintillans blooms occurred in spring (March, April, and May) and summer (June, July, and August). Among environmental factors, the dissolved inorganic phosphate, dissolved silicate and chemical oxygen demand were significantly correlated with the cell density of N. scintillans during N. scintillans blooms, and most of N. scintillans blooms were recorded in the temperature range of 18.0–25.0°C. Precipitation, hydrodynamics, water temperature, and food availability might be the main factors affecting the spatial–temporal distribution of N. scintillans blooms along the Chinese coast.     

Metagenomic insights into the alteration of soil N-cycling-related microbiome and functions under long-term conversion of cropland to Miscanthus

Miscanthus spp. show excellent application prospects due to its bioenergy potential and multiple ecological services. Annual N export with biomass harvest from Miscanthus, even without fertilizer supplement, do not reduce soil N levels. The question arises regarding how Miscanthus can maintain stable soil N levels. Metagenomic strategies were used to reveal soil N-cycling-related microbiome and their functional contributions to processes of soil N-cycling based on the comparison among the bare land, cropland, 10-year Miscanthus × giganteus, and 15-year Miscanthus sacchariflorus fields. The results showed that, after long-term cropland-to-Miscanthus conversion (LCMC), 16 of 21 bacterial phyla and all the archaeal phyla exhibited significant changes. Soil microbial denitrification and nitrification functions were significantly weakened, and N fixation (NF) was significantly enhanced. The biosynthesis of amino acids, especially alanine, aspartate, and glutamate metabolism, in soil N-cycling-related microbiome was dramatically promoted. The genus Anaeromyxobacter contributed largely to the NF process after LCMC. Variations in the soil available potassium, available N, organic C, and total N contents drove a functional shift of soil microbiome from cropland to Miscanthus pattern. We conclude that Miscanthus can recruit Anaeromyxobacter communities to enhance NF benefiting its biomass sustainability and soil N balance.     

MiR‐16, as a potential NF‐κB‐related miRNA,exerts anti‐inflammatory effects on LPS‐induced myocarditis via mediating CD40 expression: A preliminary study

The purpose of this study was to investigate the biological effect of miR‐16 on myocarditis and the underlying molecular mechanism. H9c2 cells were treated with 10 µg/mL lipopolysaccharide (LPS) for 12 hours to form a myocarditis injury model. We observed that LPS treatment distinctly decreased the level of miR‐16 in H9c2 cells. Upregulation of miR‐16 increased cell proliferation and reduced cell apoptosis. Then, CD40 was predicted and verified as a target gene of miR‐16 by TargetScan and luciferase reporter assay, respectively. Furthermore, the messenger RNA and protein expression of CD40 are negatively regulated by miR‐16. The relative expression of inflammatory factors was dramatically decreased by the miR‐16 mimic. Cells cotransfected with miR‐16 mimic and si‐CD40 could significantly abolish the injury of cardiomyocytes caused by myocarditis. Our study illustrated that the upregulation of miR‐16 has a protective effect on LPS‐damaged H9c2 cells, which may be achieved by regulating CD40 and the nuclear factor kappa B pathway.     

Absent in melanoma 2 enhances anti‐tumour effects of CAIX promotor controlled conditionally replicative adenovirus in renal cancer

Conditionally replicative adenoviruses (CRAds) were promising approach for solid tumour treatment, but its oncolytic efficiency and toxicity are still not satisfactory for further clinical application. Here, we developed the CAIX promotor (CAIX^promotor)‐controlled CRAd armed with a tumour suppressor absent in melanoma 2 (AIM2) to enhance its oncolytic potency. The CAIX^promotor‐AIM2 adenoviruses (Ad‐CAIX^promotor‐AIM2) could efficiently express E1A and AIM2 in renal cancer cells. Compared with Ad‐CAIX^promotor, Ad‐CAIX^promotor‐AIM2 significantly inhibited cell proliferation and enhanced cell apoptosis and cell killing, thus resulting in the oncolytic efficiency in 786‐O cells or OSRC‐2 cells. To explore the therapeutic effect, various Ads were intratumourally injected into OSRC‐2‐xenograft mice. The tumour growth was remarkably inhibited in Ad‐CAIX^promotor‐AIM2‐treated group as demonstrated by reduced tumour volume and weight with a low toxicity. The inflammasome inhibitor YVAD‐CMK resulted in the reduction of anti‐tumour activity by Ad‐CAIX^promotor‐AIM2 in vitro or in vivo, suggesting that inflammasome activation response was required for the enhanced therapeutic efficiency. Furthermore, lung metastasis of renal cancer mice was also suppressed by Ad‐CAIX^promotor‐AIM2 treatment accompanied by the decreased tumour fossil in lung tissues. These results indicated that the tumour‐specific Ad‐CAIX^promotor‐AIM2 could be applied for human renal cancer therapy. The therapeutic strategy of AIM2‐based CRAds could be a potential and promising approach for the therapy of primary solid or metastasis tumours.     

Nitric oxide and hydrogen peroxide are important signals mediating the allelopathic response of Arabidopsis to p‐hydroxybenzoic acid

Both nitric oxide (NO) and hydrogen peroxide (H₂O₂) are important signals that mediate plant response to environmental stimulation. Their role in plants' allelopathic interactions has also been reported, but the underlying mechanism remains little understood. p‐Hydroxybenzoic acid (pHBA) has been proposed to be an allelopathic chemical. Here, we found that pHBA at 0.4 mM efficiently suppressed Arabidopsis growth. Meanwhile, pHBA rapidly induced the accumulation of NO and H₂O₂, where such effect could be reversed by NO or H₂O₂ metabolism inhibitors or scavengers. Also, pHBA‐induced NO and H₂O₂ could be compromised in NO synthesis mutants noa1, nia1 and nia2, or H₂O₂ metabolism mutant rbohD/F, but suppressing NO accumulation with a NO synthesis inhibitor or using NO synthesis‐related mutants did not reduce pHBA‐induced H₂O₂ accumulation. Furthermore, we found that the effect of pHBA on allelopathic inhibition of growth was aggravated in NO/H₂O₂ metabolism‐related mutants or reducing NO/H₂O₂ by different inhibitors, whereas the addition of an NO/H₂O₂ donor could partly relieve the inhibitory effect of pHBA on the growth of wild type. However, adding only an NO donor, but not low concentration of H₂O₂ as the donor, could relieve the inhibitory effect of pHBA on root growth in NO metabolism mutants. On the basis of these results, we propose that both NO and H₂O₂ are important signals that mediate Arabidopsis response to the allelopathic chemical pHBA, where during this process H₂O₂ may work upstream of the NO signal.     

Neuroligin Trafficking Deficiencies Arising from Mutations in the α/β-Hydrolase Fold Protein Family

Despite great functional diversity, characterization of the α/β-hydrolase fold proteins that encompass a superfamily of hydrolases, heterophilic adhesion proteins, and chaperone domains reveals a common structural motif. By incorporating the R451C mutation found in neuroligin (NLGN) and associated with autism and the thyroglobulin G2320R (G221R in NLGN) mutation responsible for congenital hypothyroidism into NLGN3, we show that mutations in the α/β-hydrolase fold domain influence folding and biosynthetic processing of neuroligin3 as determined by in vitro susceptibility to proteases, glycosylation processing, turnover, and processing rates. We also show altered interactions of the mutant proteins with chaperones in the endoplasmic reticulum and arrest of transport along the secretory pathway with diversion to the proteasome. Time-controlled expression of a fluorescently tagged neuroligin in hippocampal neurons shows that these mutations compromise neuronal trafficking of the protein, with the R451C mutation reducing and the G221R mutation virtually abolishing the export of NLGN3 from the soma to the dendritic spines. Although the R451C mutation causes a local folding defect, the G221R mutation appears responsible for more global misfolding of the protein, reflecting their sequence positions in the structure of the protein. Our results suggest that disease-related mutations in the α/β-hydrolase fold domain share common trafficking deficiencies yet lead to discrete congenital disorders of differing severity in the endocrine and nervous systems.