Hypoxia and free radicals, such as reactive oxygen and nitrogen species, can alter the function and/or activity of the transcription factor hypoxia-inducible factor 1 (HIF1). Interplay between free ...radicals, hypoxia and HIF1 activity is complex and can influence the earliest stages of tumour development. The hypoxic environment of tumours is heterogeneous, both spatially and temporally, and can change in response to cytotoxic therapy. Free radicals created by hypoxia, hypoxia-reoxygenation cycling and immune cell infiltration after cytotoxic therapy strongly influence HIF1 activity. HIF1 can then promote endothelial and tumour cell survival. As discussed here, a constant theme emerges: inhibition of HIF1 activity will have therapeutic benefit.
•The numbers of fish species identified using eDNA metabarcoding (214) were 2.38 times those identified with bottom trawling (90).•eDNA metabarcoding can be applied to monitor the fish communities' ...spatial and temporal variability.•eDNA metabarcoding can reveal community-environmentrelationships in estuarine ecosystems.
Environmental DNA (eDNA) metabarcoding has been used to study fish diversity in various aquatic ecosystems. However, studies on fish community structure in estuarine ecosystems have not been well corroborated by eDNA metabarcoding, and comparisons with bottom trawling are lacking. We used eDNA sequencing of mitochondrial 12S rRNA gene to investigate the fish species composition and relative abundance, community temporal and spatial variations, and community-environment relationship of the Pearl River Estuary during spring and autumn. Then, we compared these results with those obtained by bottom trawling. Results showed that eDNA metabarcoding detected more species (214 vs 90), genera (148 vs 69), families (67 vs 38), and a significantly greater number of species at each station. Results of nonmetric multidimensional scaling and permutational multivariate analysis of variance based on the Bray-Curtis dissimilarity index indicated that eDNA metabarcoding detected significant differences in fish communities between spring and autumn, which was similar to the bottom trawling results. eDNA metabarcoding revealed that the fish community differences increased with spatial distance among stations. However, when we compared results of the two methods using principal coordinates analysis, we observed discordance in the fish community differences among sites. eDNA metabarcoding may provide new insights into and a more detailed and comprehensive understanding of estuarine ecosystems. Additionally, eDNA metabarcoding revealed that salinity and temperature were closely linked to fish community composition in spring, and salinity and dissolved oxygen were closely associated with fish community composition in autumn. In conclusion, eDNA metabarcoding may represent an important supplementary method, or even replace current methods, to monitor and assess temporalandspatialvariation of fish communities and infer the community-environment relationship, especially in estuarine ecosystems, which are difficult to sample using traditional methods.
Glioblastomas are lethal cancers characterized by florid angiogenesis promoted in part by glioma stem cells (GSCs). Because hypoxia regulates angiogenesis, we examined hypoxic responses in GSCs. We ...now demonstrate that hypoxia-inducible factor HIF2α and multiple HIF-regulated genes are preferentially expressed in GSCs in comparison to non-stem tumor cells and normal neural progenitors. In tumor specimens, HIF2α colocalizes with cancer stem cell markers. Targeting HIFs in GSCs inhibits self-renewal, proliferation, and survival in vitro, and attenuates tumor initiation potential of GSCs in vivo. Analysis of a molecular database reveals that
HIF2A expression correlates with poor glioma patient survival. Our results demonstrate that GSCs differentially respond to hypoxia with distinct HIF induction patterns, and HIF2α might represent a promising target for antiglioblastoma therapies.
miR-139-5p has a tumor suppressor effect in some cancers and negatively regulates CXCR4. To this end, we examined the expression and mechanism of of action of miR-139-5p and CXCR4 in oral squamous ...cell carcinoma (OSCC). miRNA-139-5p was down-regulated whereas CXCR4 was increased in tissues and cells of OSCC. Moreover, low expression of miR-139-5p was associated with a low survival. Overexpression of miR-139-5p in OSCC inhibited
and
cell proliferation and
mobility of OSCC and inhibited the expression of WNT responsive c-myc, cyclinD1, and Bcl-2, and such effects were all reversible by an inhibitor of miR-139-5p or over-expression of CXCR4. The inverse relation between expression of miR-139-5p and CXCR4 might be related to the fact that miR-139-5p negatively regulates CXCR4 expression by virtue of direct binding. These findings underscore the importance of miR-139-5p and CXCR4 in regulation of OSCC.
Numerous studies have found an association between autoimmune diseases of the nervous system (ADNS) and schizophrenia (SCZ), but the findings remain controversial. We conducted the first ...meta-analysis to summarize the current evidence from cohort studies that evaluated the association between ADNS and SCZ.
PubMed, Web of Science, and Embase were comprehensively searched until May 30, 2022 for articles on the association between ADNS and SCZ. Every included study was reported effect size with 95% CIs for the association between ADNS and SCZ. Meta-regression and subgroup analysis were used to assess the heterogeneity.
A total of 8 cohort studies with 12 cohorts were included in the meta-analysis. We observed a significant association between ADNS and SCZ (RR = 1.42; 95%CI, 1.18–1.72). Subgroup analysis showed that the risk of SCZ was significantly increased when ADNS were used as exposure factors (RR = 1.48; 95%CI, 1.15–1.89), whereas with SCZ did not observe an increased risk of subsequent ADNS (RR = 1.33; 95%CI, 0.92–1.92); multiple sclerosis (MS) was positively associated with SCZ (RR = 1.36; 95%CI, 1.12–1.66), but no significant association was found between Guillain-Barre syndrome (GBS) and SCZ (RR = 1.90; 95%CI, 0.87–4.17). Meanwhile, we found location was the source of heterogeneity.
High heterogeneity was observed (I2 = 92.0%), and only English literature was included in the meta-analysis.
We found a positive association between ADNS and SCZ, and the association was different across the different types of ADNS. The results of the study are helpful for clinicians to carry out targeted preventive measures for ADNS and SCZ.
•Meta-analysis on the association between ADNS and SCZ from cohort studies was first conducted•A positive association between ADNS and SCZ was confirmed•The association was different across study outcomes and specific types of ADNS
Purpose: The present study was performed to compare the optical quality of the eyes of myopic children before and after treatment with atropine eye drops of different concentrations. Methods: In the ...study population of 71 patients (131 eyes), 34 patients (63 eyes) were given 0.01% atropine eye drops and 37 patients (68 eyes) were given 0.05% atropine eye drops. The modulation transfer function (MTF) cutoff frequency, Strehl ratio, objective scattering index (OSI), and predicted visual acuities (PVAs 100%, 20%, and 9%) under different lighting conditions were measured before and after two weeks of atropine treatment. Results: After using 0.05% atropine eye drops for two weeks, the Strehl ratio decreased from 0.27 ± 0.07 to 0.23 ± 0.07 (P = 0.0026), PVA 20% decreased from 1.15 ± 0.32 to 1.03 ± 0.36 (P = 0.0344), and PVA 9% decreased from 0.74 ± 0.23 to 0.64 ± 0.23 (P = 0.0073). The OSI was significantly higher after using 0.05% than 0.01% atropine eye drops (P = 0.0396), while both the Strehl ratio and PVA 20% were lower after using 0.05% than 0.01% atropine eye drops (P = 0.0087 and P = 0.0492, respectively). Conclusion: The children's optical quality did not change significantly after using 0.01% atropine eye drops, whereas it decreased after using 0.05% atropine eye drops.
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•Accurate subspecies identification of free-ranging whales can be achieved using noninvasive eDNA technology.•Various mtDNA markers in eDNA can be used for genetic identification of ...cetaceans and reconstruction of their phylogenies.•Eden’s whale might mainly fed on sardines and anchovies in Dapeng Bay, Guangdong Province, China.•eDNA technology is potentially useful as an early warning system for the presence of cetaceans.
Environmental DNA (eDNA) sampling of water is a powerful method for comprehensive and noninvasive monitoring of aquatic animal species. However, there have been few reports of its application to cetacean species. On June 29, 2021, a whale (nicknamed Xiaobu) appeared in Dapeng Bay off Guangdong Province, China. We used eDNA technology to obtain information related to this whale (e.g., species identification and food resources) and to trace its possible origin. Fragments of four whale mitochondrial sequences (12S rDNA, 16S rDNA, cytochrome c oxidase subunit 1, and control region) were obtained from amplicons of eDNA collected in Dapeng Bay; sequence barcoding showed that this was an Eden’s whale (Balaenoptera edeni edeni Anderson 1879). Analysis of potential prey species (PPS) suggested that this whale might enter Dapeng Bay while tracking prey, mainly sardines (Sardinella lemuru, Sardinella gibbosa and Sardinella jussieui) and anchovies (Thryssa dussumieri, Thryssa vitrirostris and Thryssa kammalensis). Retrieval of eDNA metabarcoding data from samples collected in waters adjacent to Dapeng Bay (i.e. Lingding Bay and Daya Bay) revealed that Eden’s whale had appeared outside Lingding Bay up to 2 months prior to the appearance of this whale in Dapeng Bay (early April 2021). Overall, this study showed that eDNA is a highly effective noninvasive survey method for the accurate identification of target cetacean species and prey composition; it can be used to monitor megafauna that are under strict legal protection or to monitor megafauna with unknown conditions.
To assess the feasibility and clinical utility of artificial intelligence (AI)-based screening for diabetic retinopathy (DR) and macular edema (ME) by combining fundus photos and optical coherence ...tomography (OCT) images in a community hospital. Fundus photos and OCT images were taken for 600 diabetic patients in a community hospital. Ophthalmologists graded these fundus photos according to the International Clinical Diabetic Retinopathy (ICDR) Severity Scale as the ground truth. Two existing trained AI models were used to automatically classify the fundus images into DR grades according to ICDR, and to detect concomitant ME from OCT images, respectively. The criteria for referral were DR grades 2-4 and/or the presence of ME. The sensitivity and specificity of AI grading were evaluated. The number of referable DR cases confirmed by ophthalmologists and AI was calculated, respectively. DR was detected in 81 (13.5%) participants by ophthalmologists and in 94 (15.6%) by AI, and 45 (7.5%) and 53 (8.8%) participants were diagnosed with referable DR by ophthalmologists and by AI, respectively. The sensitivity, specificity and area under the curve (AUC) of AI for detecting DR were 91.67%, 96.92% and 0.944, respectively. For detecting referable DR, the sensitivity, specificity and AUC of AI were 97.78%, 98.38% and 0.981, respectively. ME was detected from OCT images in 49 (8.2%) participants by ophthalmologists and in 57 (9.5%) by AI, and the sensitivity, specificity and AUC of AI were 91.30%, 97.46% and 0.944, respectively. When combining fundus photos and OCT images, the number of referrals identified by ophthalmologists increased from 45 to 75 and from 53 to 85 by AI. AI-based DR screening has high sensitivity and specificity and may feasibly improve the referral rate of community DR.
Previous studies have demonstrated an association between anxiety and metabolic syndrome (MetS). However, the association is still controversial. This updated meta-analysis aimed to reanalyze the ...association between anxiety and MetS.
We comprehensively searched PubMed, Embase and Web of Science for all related studies published before January 23, 2023. Observational studies that informed effect size with 95% confidence interval (CI) for the association between anxiety and MetS were included. According to heterogeneity between studies, fixed or random effects models were applied to calculate the pooled effect size. Publication bias was examined by funnel plots.
The research included 24 cross-sectional studies: 20 studies used MetS as the dependent variable with a pooled OR of 1.07 (95% CI: 1.01-1.13) and four studies used anxiety as the dependent variable with a pooled OR of 1.14 (95% CI: 1.07-1.23). Three cohort studies were found: two studies detected the association of baseline anxiety with the risk of MetS, one of the studies demonstrated a significant association, but a similar result was not found in another study; one study showed no significant association between baseline MetS and the risk of anxiety.
Cross-sectional studies indicated an association between anxiety and MetS. The results from cohort studies are still inconsistent and limited. More large-scale prospective studies are needed to further reveal the causal relationship of anxiety with MetS.
Glioblastomas are the most common and most lethal primary brain tumor. Recent studies implicate an important role for a restricted population of neoplastic cells (glioma stem cells (GSCs)) in glioma ...maintenance and recurrence. We now demonstrate that GSCs preferentially express two interleukin 6 (IL6) receptors: IL6 receptor alpha (IL6Rα) and glycoprotein 130 (gp130). Targeting IL6Rα or IL6 ligand expression in GSCs with the use of short hairpin RNAs (shRNAs) significantly reduces growth and neurosphere formation capacity while increasing apoptosis. Perturbation of IL6 signaling in GSCs attenuates signal transducers and activators of transcription three (STAT3) activation, and small molecule inhibitors of STAT3 potently induce GSC apoptosis. These data indicate that STAT3 is a downstream mediator of prosurvival IL6 signals in GSCs. Targeting of IL6Rα or IL6 expression in GSCs increases the survival of mice bearing intracranial human glioma xenografts. IL6 is clinically significant because elevated IL6 ligand and receptor expression are associated with poor glioma patient survival. The potential utility of anti‐IL6 therapies is demonstrated by decreased growth of subcutaneous human GSC‐derived xenografts treated with IL6 antibody. Together, our data indicate that IL6 signaling contributes to glioma malignancy through the promotion of GSC growth and survival, and that targeting IL6 may offer benefit for glioma patients. STEM CELLS 2009;27:2393–2404
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