Circ_0090231 knockdown protects vascular smooth muscle cells from ox-LDL-induced proliferation, migration and invasion via miR-942-5p/PPM1B axis during atherosclerosis.

Atherosclerosis (AS) is a dominant pathological basis of cardiovascular disease. Circular RNAs (circRNAs) have been proposed to have crucial functions in regulating pathological progressions of AS. Hence, the aim of this study was to investigate the potential function of circ_0090231 in AS progression. Oxidized low densitylipoprotein (ox-LDL)-challenged vascular smooth muscle cells (VSMCs) were used for in vitro functional analysis. Levels of genes and proteins were measured by qRT-PCR and Western blot. The proliferation, migration and invasion were assessed using cell counting kit-8, 5-ethynyl-2'-deoxyuridine, and transwell assays. The interaction between miR-942-5p and circ_0090231 or PPM1B (Protein Phosphatase, Mg2+/Mn2+ Dependent 1B) was evaluated by dual-luciferase reporter and pull-down assays. Circ_0090231 is a stable circRNA, and was increased in the serum of AS patients and ox-LDL-challenged VSMCs. Functionally, silencing of circ_0090231 could reverse ox-LDL-induced proliferation, migration and invasion in VSMCs. Mechanistically, circ_0090231 directly targeted miR-942-5p, and PPM1B was a target of miR-942-5p. Besides, circ_0090231 sequestered miR-942-5p to release PPM1B expression, suggesting the circ_0090231/miR-942-5p/PPM1B axis. Further rescue experiments showed that miR-942-5p inhibition or ectopic overexpression of PPM1B dramatically attenuated the suppressing influences of circ_0090231 knockdown on VSMC proliferative, migratory and invasive abilities under ox-LDL treatment. Silencing of circ_0090231 could reverse ox-LDL-induced proliferation, migration and invasion in VSMCs via miR-942-5p/PPM1B axis, providing a theoretical basis for elucidating the mechanism of AS process.

Facilitation of axonal transcriptome analysis with quantitative microfluidic devices.

Microfluidic chambers are powerful tools for studying axonal mRNA localization and translation in neurons. In addition to specific manipulation and measurements of axons, microfluidic chambers are used for collecting axonal materials to perform axonal transcriptome analysis. However, traditional bipartite and tripartite chambers have limitations either in purity or quantity of collected axons. Here, we improved the design of traditional chambers. Moreover, we developed two new quantitative chambers, multi-compartmental quantitative bipartite chamber (MQBC) and long quantitative tripartite chamber (LQTC). Compared with the traditional chambers, MQBC and LQTC could dramatically increase the efficiency in collecting axonal RNA. Finally, we applied these chambers to do comparative axon transcriptome analysis of different types of neurons. Thus, our newly designed quantitative chambers significantly improve axon collection efficiency and facilitate axonal transcriptome analysis.

YTHDF2 in dentate gyrus is the m6A reader mediating m6A modification in hippocampus-dependent learning and memory.

N6-methyladenosine (m6A) has been demonstrated to regulate learning and memory in mice. To investigate the mechanism by which m6A modification exerts its function through its reader proteins in the hippocampus, as well as to unveil the specific subregions of the hippocampus that are crucial for memory formation, we generated dentate gyrus (DG)-, CA3-, and CA1-specific Ythdf1 and Ythdf2 conditional knockout (cKO) mice, respectively. Surprisingly, we found that only the DG-specific Ythdf2 cKO mice displayed impaired memory formation, which is inconsistent with the previous report showing that YTHDF1 was involved in this process. YTHDF2 controls the stability of its target transcripts which encode proteins that regulate the elongation of mossy fibers (MF), the axons of DG granule cells. DG-specific Ythdf2 ablation caused MF overgrowth and impairment of the MF-CA3 excitatory synapse development and transmission in the stratum lucidum. Thus, this study identifies the m6A reader YTHDF2 in dentate gyrus as the only regulator that mediates m6A modification in hippocampus-dependent learning and memory.

Superb Microvascular Imaging for the Differentiation of Benign and Malignant Breast Lesions: A System Review and Meta-Analysis.

OBJECTIVE: To evaluate the diagnostic performance of SMI in the diagnosis of benign and malignant breast lesions. METHODS: A systematic search of PubMed, EMBASE, Cochrane, OVID, SCI, and SCOPUS was performed to find relevant studies which applied SMI to differentiate benign and malignant breast lesions. All the studies were published before October 10, 2022. Only studies published in English were collected. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was applied to assess the quality of the included studies. Summary receiver operating characteristic (SROC) modeling was also performed to the diagnostic performance of SMI in the diagnosis of benign and malignant breast lesions. Subgroup analyses and meta-regression were performed to find out the heterogeneity. RESULTS: Twenty studies which include a total of 2873 lesions (1748 benign and 1125 malignant) in 2740 patients were evaluated in this meta-analysis. The summary sensitivity and specificity were 0.82 (95% confidence interval [CI]: 0.76-0.86), 0.70 (95% CI: 0.64-0.76) for SMI vascular degree, 0.77 (95% CI: 0.67-0.84), 0.79 (95% CI: 0.75-0.83) for SMI vascular distribution, 0.78 (95% CI: 0.70-0.84), 0.75 (95% CI: 0.69-0.80) for SMI vascular morphology, 0.81 (95% CI: 0.72-0.87), 0.80 (95% CI: 0.75-0.85) SMI penetration vessel. For SMI overall vascular features, the summary sensitivity and summary specificity were 0.74 (95% CI: 0.61-0.84) and 0.80 (95% CI: 0.76-0.84). The result of subgroup analysis and meta-analysis showed malignant rate and country might be the cause of heterogeneity of diagnostic accuracy of vascular grade and morphology. CONCLUSION: SMI vascular features have high sensitivity and specificity in the differentiation of benign and malignant lesions. Future international multicenter studies in various regions with large sample size are required to confirm these findings.

m6A regulation of cortical and retinal neurogenesis is mediated by the redundant m6A readers YTHDFs.

m6A modification plays an important role in regulating mammalian neurogenesis. However, whether and how the major cytoplasmic m6A readers, YTHDF1, YTHDF2, and YTHDF3 mediate this process is still not clear. Here, we demonstrate that Ythdf1 and Ythdf2 double deletion but not individual knockout recapitulates the phenotype of Mettl14 knockout in cortex. In addition, we find that Mettl14 knockout in retina causes protracted proliferation of retinal progenitors, decreased numbers of retinal neurons, and disturbed laminar structure. This phenotype is only reproduced when Ythdf1, Ythdf2, and Ythdf3 are knocked out simultaneously in retina. Analysis of YTHDF target mRNAs in mouse cortex and retina reveals abundant overlapping mRNAs related to neurogenesis that are recognized and regulated by both YTHDF1 and YTHDF2. Together our results demonstrate that the functionally redundant YTHDFs mediate m6A regulation of cortical and retinal neurogenesis.

Recycling of spent mushroom substrate: Utilization as feed material for the larvae of the yellow mealworm Tenebrio molitor (Coleoptera: Tenebrionidae).

Spent mushroom substrate is made from the waste remaining after the harvest of mushrooms. Here, we evaluated the potential of five spent edible fungi (Auricularia cornea, Lentinus edodes, Pleurotus eryngii, P. citrinopileatus and P. ostreatus) substrates as feed sources for Tenebrio molitor larvae. Young larvae did not survive on any substrate except the spent L. edodes substrate (36.7%). The survival rates in young larvae were similar among the different diets in which wheat bran or rice bran was replaced with 0, 20, 30, 40, 50, or 60% spent L. edodes substrate. The weights of the surviving larvae were decreased only when 70% of wheat bran and > 40% of rice bran was replaced with spent L. edodes substrate. In addition, the middle-aged larvae fed wheat bran only were significantly larger than those fed diets with 30~60% spent L. edodes substrate in dry feed, but the larvae of all treatments failed to pupate. Whereas the green feed was added in dry feed, there were no significant differences in pupal weight, pupation rate, pupal duration, adult emergence, or deformed adults among the three treatments in middle-aged larvae that were fed on diets containing 0, 30, or 40% spent L. edodes substrate. Collectively, these results suggest that spent L. edodes substrate has considerable potential to be used as a partial replacement (< 40%) of conventional feed for T. molitor, and spent mushroom substrate waste may be recycled as feed material for resource insects.

Optimized pupal age of Tenebrio molitor L. (Coleoptera: Tenebrionidae) enhanced mass rearing efficiency of Chouioia cunea Yang (Hymenoptera: Eulophidae).

Chouioia cunea Yang (Hymenoptera: Eulophidae) has been widely used for biological control of the fall webworm, Hyphantria cunea (Drury) (Lepidoptera: Arctiidae), in China. The yellow mealworm, Tenebrio molitor L. (Coleoptera: Tenebrionidae), an important resource insect species distributed worldwide, is considered to be a potential alternative host for mass rearing of C. cunea to the Chinese oak silkworm, Antheraea pernyi (Guerin-Meneville) (Lepidoptera: Saturniidae), which is currently used. In this study, we investigated the effects of host age on C. cunea mass rearing by measuring parasitism, development and adult fertility of C. cunea on T. molitor pupae of different ages. The results showed no significant differences in the percentage of parasitized hosts and developmental time of C. cunea in pupae of different ages. However, the number of C. cunea adults (137.2-154.7 adults per host) that emerged from 0, 1, and 2-day-old pupae was significantly higher than that from 4-day-old pupae. The lowest percentages of unemerged adults were found in 2-day-old (1.2%) and 3-day-old (1.4%) pupae, which were significantly lower than that of 4-day-old pupae (10.3%). The emergence of adult females from 0 to 2-day-old pupae (120.2-142.3 per pupa) was significantly higher than that from 4-day-old hosts (64.6). Adult females emerging from 2-day-old pupae carried significantly more eggs (258.2 eggs/female) than those from 0 and 1-day-old pupae (178.4-178.9 eggs/female). Our findings indicated that 2-day-old pupae of T. molitor were most suitable to rear C. cunea. Overall, this research provided valuable information to optimize pupae for the mass rearing of C. cunea on host T. molitor.