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Angiopoietin‐like protein (ANGPTL) 4 is a key factor in the regulation of lipid and glucose metabolism in metabolic diseases. ANGPTL4 is highly expressed in various cancers, but the regulation of energy metabolism in tumours remains to be determined. This study explored the role of ANGPTL4 in aerobic glycolysis, glutamine consumption and fatty acid oxidation in nonsmall cell lung cancer (NSCLC) cells. Two NSCLC cell lines (A549 and H1299) were used to investigate the role of ANGPTL4 in energy metabolism by tracer techniques and with Seahorse XF technology in ANGPTLs4 knockdown cells. RNA microarrays and specific inhibitors were used to identify targets in ANGPTLs4‐overexpressing cells. The results showed that knockdown of ANGPTLs4 could inhibit energy metabolism and proliferation in NSCLC. ANGPTLs4 had no significant effect on glycolysis but affected glutamine consumption and fatty acid oxidation. Knockdown of ANGPTLs4 also significantly inhibited tumour metastasis and energy metabolism in mice and had a weak effect on glycolysis. RNA microarray analysis showed that ANGPTLs4 significantly affected glutaminase (GLS) and carnitine palmitoyl transferase 1 (CPT1). ANGPTLs4‐overexpressing cells were exposed to a glutamine deprivation environment, and cell proliferation and energy metabolism were significantly decreased but still differed from normal NSCLC cells. Treatment of ANGPTLs4‐overexpressing cells with GLS and CPT1 inhibitors simultaneously prevented the regulatory effects on cell proliferation and energy metabolism. ANGPTLs4 could promote glutamine consumption and fatty acid oxidation but not glycolysis or accelerate energy metabolism in NSCLC.

Aims Efforts to concurrently test for enemy release of both above- and belowground enemies for invasive plants in non-native range are limited. Moreover, direct evidence for the causal link between enemy release and performance is rare for invasive plants. Thus, we sought to investigate if above- and/or belowground enemies are involved in the enemy release mechanisms at various life stages of a temperate invader and their consequences on plant community properties. Methods We conducted field surveys of enemy damage and plant performance, and plant-soil feedback experiments in the glasshouses using Ambrosia trifida in both its non-native and native ranges across the seed, seedling, and adult life stages. Results Field surveys showed that seeds of A. trifida were more severely damaged by aboveground enemies in the native relative to the non-native range, while the difference in leaf damage between ranges was small. Plant-soil feedback experiments showed that release from belowground enemies was also important, as seed germination and plant growth were significantly reduced in soils from the native range compared with soils from the non-native range. Consistent with the above results, A. trifida was larger, produced more seeds, had higher density, and exerted stronger impacts on co-occurring native plants in the non-native relative to the native range. Conclusion Our results demonstrated that release from both above- and belowground enemies at various life stages contributed to the invasion success of A. trifida in its non-native range and highlighted the importance of considering both above- and belowground enemy release when studying plant invasions.

Atmospheric nitrogen (N) deposition has often been considered as a driver of exotic plant invasions. However, most related studies focused on the effects of soil N levels, and few on those of N forms, and few related studies were conducted in the fields. In this study, we grew , a notorious invader in arid/semi-arid and barren habitats, and two coexisting native plants and in mono- and mixed cultures in the fields in Baicheng, northeast China, and investigated the effects of N levels and forms on the invasiveness of . Compared with the two native plants, had higher aboveground and total biomass in both mono- and mixed monocultures under all N treatments, and higher competitive ability under almost all N treatments. N addition enhanced the growth and competitive advantage of the invader under most conditions, and facilitated invasion success of . The growth and competitive ability of the invader were higher under low nitrate relative to low ammonium treatment. The advantages of the invader were associated with its higher total leaf area and lower root to shoot ratio compared with the two native plants. The invader also had a higher light-saturated photosynthetic rate than the two native plants in mixed culture (not significant under high nitrate condition), but not in monoculture. Our results indicated that N (especially nitrate) deposition may also promote invasion of exotic plants in arid/semi-arid and barren habitats, and the effects of N forms and interspecific competition need to be taken into consideration when studying the effects of N deposition on invasion of exotic plants.

The biotic resistance hypothesis proposes that species-rich communities are more resistant to biological invasions due to the less available resources for invaders. The variation in available soil resources may affect the invasion resistance of community, but there is little evidence. Using invasive Solanum rostratum Dunal, a noxious invader in infertile habitats, and six co-occurring non-invasive species, we conducted a field experiment by testing the relationship between relative growth performance of invasives and richness of resident non-invasives, and the effects of available soil water and nutrients on the relationship. We found that relative aboveground biomass (hereafter relative biomass), relative coverage, community-weighted means (CWM) of specific leaf area (SLA), and photosynthetic rate (Pmass) of S. rostratum decreased with increasing resident non-invasive species richness. In contrast, for the non-invasive species, the CWM of SLA and Pmass significantly increased with increasing resident species richness. However, the available soil water and nutrients exerted limited effects on the relative biomass and coverage of S. rostratum. The piecewise structural equation model showed that non-invasive species richness has not only direct negative effects, but also indirect negative effects through promoting non-invasive biomass on the relative biomass of S. rostratum. Our findings indicate that the higher resident species richness is fundamental to resist invasion of alien S. rostratum, which operates through increasing biomass and resource acquisitive traits of a non-invasive community. Additionally, soil available resources exert limited effects on the invasion resistance. This study suggests the importance of conservation of biodiversity in preventing biological invasions.

Due to heavy metals’ magnified pollution from their accumulation in the ecosystem, practical detection of ultra-low concentration of heavy metals in environmental sample is of great significance for environmental supervision and maintenance of people’s health. Herein, a practical and sensitive assay of heavy metal mercury was developed by visually observing (or spectrum detecting) the change of cationic gold nanoparticles (AuNPs), which is directly caused by mercury ion induced hybridization between non-canonical base pairs. In this assay, signal probe’s response was direct rather than the indirect salt induction, thus avoiding the defect of salt-induced indirect response. It makes the analysis more sensitive. The results showed that the response of 8.2 × 10−8 M Hg2+ could be observed with naked eye and the detection limit of Hg2+ in spectrometric determination was 4.9 × 10−11 M, which is more than one order of magnitude lower than that from indirect response pattern of signal probe. In addition, high specificity of the affinity chemistry for T–Hg–T renders the assay to be highly selective. Compared with the results of cold vapor atom adsorption spectroscopy (CVAAS), this analysis has good reliability for the detection of mercury. The results fully indicate that the developed assay is an ideal alternative for online detection of heavy metal mercury in environmental pollution samples.

BackgroundNumerous variants of uncertain significance (VUSs) have been identified by whole exome sequencing in clinical practice. However, VUSs are not currently considered medically actionable.ObjectiveTo assess the splicing patterns of 49 VUSs in 48 families identified clinically to improve genetic counselling and family planning.MethodsForty-nine participants with 49 VUSs were recruited from the Reproductive and Genetic Hospital of CITIC-Xiangya. Bioinformatic analysis was performed to preliminarily predict the splicing effects of these VUSs. RT-PCR and minigene analysis were used to assess the splicing patterns of the VUSs. According to the results obtained, couples opted for different methods of reproductive interventions to conceive a child, including prenatal diagnosis and preimplantation genetic testing (PGT).ResultsEleven variants were found to alter pre-mRNA splicing and one variant caused nonsense-mediated mRNA decay, which resulted in the reclassification of these VUSs as likely pathogenic. One couple chose to undergo in vitro fertilisation with PGT treatment; a healthy embryo was transferred and the pregnancy is ongoing. Three couples opted for natural pregnancy with prenatal diagnosis. One couple terminated the pregnancy because the fetus was affected by short-rib thoracic dysplasia and harboured the related variant. The infants of the other two couples were born and were healthy at their last recorded follow-up.ConclusionRNA splicing analysis is an important method to assess the impact of sequence variants on splicing in clinical practice and can contribute to the reclassification of a significant proportion of VUSs. RNA splicing analysis should be considered for genetic disease diagnostics.

Background High-intensity focused ultrasound cyclo-plasty (UCP) is a recently developed glaucoma surgery. This study collected and analysed the clinical data of patients who underwent UCP to observe the efficacy and safety of this surgery in Chinese glaucoma patients. Methods This was a retrospective study. The clinical data of all the patients who underwent UCP at Affiliated Foshan Hospital, Southern Medical University, were collected and analysed to evaluate the efficacy and safety of UCP. The main outcome measure was intraocular pressure, and the secondary outcome measures were best corrected visual acuity (logMAR) and complications. Results Fifty-eight patients (61 eyes) were recruited for this study. IOP was dramatically decreased during the 12 months after UCP ( p <0.05). The median IOP reduction during the 18 months post-procedure was more than 30%. The greatest reduction was at 1 month post-UCP (60.86%). The qualified success rate was more than 60% during the 18-month follow-up (Fig. 1). Poor follow up was found after 6-month post-UCP. The highest success rate was obtained at 7 days post-UCP (94.55%). No statistically significant decrease in BCVA in the vison group was observed at the follow-up visits, except for 1 day post-UCP. There was a statistically significant reduction in the use of IOP lowering medications during the 6 months post-UCP. No severe complications occurred. Conclusion UCP is a safe and effective procedure for primary and refractive glaucoma at least during the 6 months post-UCP procedure. Studies with longer follow-up time and better follow up are needed to further confirm the long-term efficacy and safety of UCP in Chinese glaucoma patients.

Candida albicans ( C. albicans ) is a ubiquitous clinical fungal pathogen. In recent years, combination therapy, a potential treatment method to overcome C. albicans resistance, has gained traction. In this study, we synthesized a series of cyclometalated iridium(III) complexes with the formula [Ir(C-N) 2 (tpphz)](PF 6 ) (C-N = 2-phenylpyridine (ppy, in Ir1 ), 2-(2-thienyl)pyridine (thpy, in Ir2 ), 2-(2,4-difluorophenyl) pyridine (dfppy, in Ir3 ), tpphz = tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine) and polypyridyl ruthenium(II) complexes with the formula [Ru(N-N) 2 (tpphz)](PF 6 ) 2 (N-N = 2,2'-bipyridine (bpy, in Ru1 ), 1,10-phenanthroline (phen, in Ru2 ), 4,7-diphenyl-1,10-phenanthroline (DIP, in Ru3 )), and investigated their antifungal activities against drug-resistant C. albicans and their combination with fluconazole (FLC). Of which, the combination of the lead iridium(III) complex Ir2 and FLC showed strong antifungal activity against drug-resistant C. albicans. Mechanism studies have shown that they can inhibit the formation of hyphae and biofilm, damage mitochondrial function and accumulate intracellular ROS. Therefore, iridium(III) complexes combined with FLC can be used as a promising treatment to exert anti-drug-resistant C. albicans activity, in order to improve the treatment efficiency of fungal infection.

Background: Zuotai (mainly β-HgS)-containing 70 Wei-Zhen-Zhu-Wan (70W, Rannasangpei) is a famous Tibetan medicine for treating cardiovascular and gastrointestinal diseases.  We have shown that 70W protected against CCl 4 hepatotoxicity.  CCl 4 is metabolized via cytochrome P450 (CYP) to produce reactive metabolites. Whether 70W has any effect on CYPs is unknown and such effects should be compared with mercury compounds for safety evaluation.   Methods: Mice were given clinical doses of 70W (0.15-1.5 g/kg, po), Zuotai (30 mg/kg, po), and compared to HgCl 2 (33.6 mg/kg, po) and MeHg (3.1 mg/kg, po) for seven days. Liver RNA and protein were isolated for qPCR and Western-blot analysis. Results: 70W and Zuotai had no effects on hepatic mRNA expression of Cyp1a2, Cyp2b10, Cyp3a11, Cyp4a10 and Cyp7a1, and corresponding nuclear receptors [aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor-α (PPARα); farnesoid X receptor (FXR)]. In comparison, HgCl 2 and MeHg increased mRNA expression of Cyp1a2, Cyp2b10, Cyp4a10 and Cyp7a1 except for Cyp3a11, and corresponding nuclear receptors except for PXR. Western-blot confirmed mRNA results, showing increases in CYP1A2, CYP2B1, CYP2E1, CYP4A and CYP7A1 by HgCl 2 and MeHg only, and all treatments had no effects on CYP3A. Conclusions: Zuotai and Zuotai-containing 70W at clinical doses had minimal influence on hepatic CYPs and corresponding nuclear receptors, while HgCl 2 and MeHg produced significant effects.  Thus, the use of total Hg content to evaluate the safety of HgS-containing 70W is inappropriate.

Regenerative medicine holds the promise of replacing damaged tissues largely by stem cell activation. Hedgehog signaling through the plasma membrane receptor Smoothened (Smo) is an important process for regulating stem cell proliferation. The development of Hedgehog-related therapies has been impeded by a lack of US Food and Drug Administration (FDA)-approved Smo agonists. Using a high-content screen with cells expressing Smo receptors and a β-arrestin2-GFP reporter, we identified four FDA-approved drugs, halcinonide, fluticasone, clobetasol, and fluocinonide, as Smo agonists that activate Hedgehog signaling. These drugs demonstrated an ability to bind Smo, promote Smo internalization, activate Gli, and stimulate the proliferation of primary neuronal precursor cells alone and synergistically in the presence of Sonic Hedgehog protein. Halcinonide, fluticasone, clobetasol, and fluocinonide provide an unprecedented opportunity to develop unique clinical strategies to treat Hedgehog-dependent illnesses.