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How do author perceptions match up to the outcomes of the peer-review process and perceptions of others? In a top-tier computer science conference (NeurIPS 2021) with more than 23,000 submitting authors and 9,000 submitted papers, we surveyed the authors on three questions: (i) their predicted probability of acceptance for each of their papers, (ii) their perceived ranking of their own papers based on scientific contribution, and (iii) the change in their perception about their own papers after seeing the reviews. The salient results are: (1) Authors had roughly a three-fold overestimate of the acceptance probability of their papers: The median prediction was 70% for an approximately 25% acceptance rate. (2) Female authors exhibited a marginally higher (statistically significant) miscalibration than male authors; predictions of authors invited to serve as meta-reviewers or reviewers were similarly calibrated, but better than authors who were not invited to review. (3) Authors' relative ranking of scientific contribution of two submissions they made generally agreed with their predicted acceptance probabilities (93% agreement), but there was a notable 7% responses where authors predicted a worse outcome for their better paper. (4) The author-provided rankings disagreed with the peer-review decisions about a third of the time; when co-authors ranked their jointly authored papers, co-authors disagreed at a similar rate-about a third of the time. (5) At least 30% of respondents of both accepted and rejected papers said that their perception of their own paper improved after the review process. The stakeholders in peer review should take these findings into account in setting their expectations from peer review., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rastogi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Long noncoding RNAs (lncRNAs) have emerged as key players in tumorigenesis and tumour progression. However, the biological functions and potential mechanisms of lncRNAs in colorectal cancer (CRC) are unclear., Methods: The novel lncRNA POU6F2-AS1 was identified through bioinformatics analysis, and its expression in CRC patients was verified via qRT-PCR and FISH. In vitro and in vivo experiments, such as BODIPY staining, Oil Red O staining, triglyceride (TAG) assays, and liquid chromatography mass spectrometry (LC-MS) were subsequently performed with CRC specimens and cells to determine the clinical significance, and functional roles of POU6F2-AS1. Biotinylated RNA pull-down, RIP, Me-RIP, ChIP, and patient-derived organoid (PDO) culture assays were performed to confirm the underlying mechanism of POU6F2-AS1., Results: The lncRNA POU6F2-AS1 is markedly upregulated in CRC and associated with adverse clinicopathological features and poor overall survival in CRC patients. Functionally, POU6F2-AS1 promotes the growth and lipogenesis of CRC cells both in vitro and in vivo. Mechanistically, METTL3-induced m 6 A modification is involved in the upregulation of POU6F2-AS1. Furthermore, upregulated POU6F2-AS1 could tether YBX1 to the FASN promoter to induce transcriptional activation, thus facilitating the growth and lipogenesis of CRC cells., Conclusions: Our data revealed that the upregulation of POU6F2-AS1 plays a critical role in CRC fatty acid metabolism and might provide a novel promising biomarker and therapeutic target for CRC., (© 2024. The Author(s).)

Purpose: Repeated exposure of infant rhesus macaques to sevoflurane induces neurotoxicity and is associated with neurocognitive impairment in later life. We aimed to investigate the effect of repeated sevoflurane exposure on the expression of proteins in the prefrontal cortex of infant rhesus macaques by proteomics., Methods: Rhesus macaques were exposed to sevoflurane three times, on postnatal days 7, 21 and 35. Quantitative proteomics employing LC-MS with isobaric labeling (TMT10plex), western blotting, and transmission electron microscopy (TEM) were utilized in the studies., Results: The results of a proteomics investigation of the brain revealed that the proteins that were differentially expressed in rhesus macaques after sevoflurane exposures were associated mainly with mitochondrial respiration. Following multiple sevoflurane exposures, the prefrontal cortices of rhesus macaques exhibited increases in NDUFA8 and COX IV protein levels, while no alterations in mitochondrial morphology were observed through TEM., Conclusion: Multiple exposures to sevoflurane increased the mitochondrial protein levels in rhesus macaques., (© 2023. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Strong evidence from human genetic studies associates the thousand and one amino acid kinase 1 (TAOK1) gene with autism spectrum disorder (ASD). In this work, we discovered a de novo frameshifting mutation in TAOK1 within a Chinese ASD cohort. We found that Taok1 haploinsufficiency induces autistic-like behaviors in mice. Importantly, we observed a significant enrichment of Taok1 in the dorsal raphe nucleus (DRN). The haploinsufficiency of Taok1 considerably restrained the activation of DRN neurons during social interactions, leading to the aberrant phosphorylation of numerous proteins. Intriguingly, the genetic deletion of Taok1 in VGlut3-positive neurons of DRN resulted in mice exhibiting autistic-like behaviors. Ultimately, reintroducing wild-type Taok1, but not its kinase-dead variant, into the DRN of adult mice effectively mitigated the autistic-like behaviors associated with Taok1 haploinsufficiency. This work suggests that Taok1, through its influence in the DRN, regulates social interaction behaviors, providing critical insights into the etiology of ASD., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Exosomes are nanoscale extracellular vesicles secreted by parent cells and they are present in most bodily fluids, are able to carry active substances through intercellular transport and mediate communication between different cells, in particular those active in cancer. Circular RNAs (circRNAs) are novel noncoding RNAs expressed in most eukaryotic cells and are involved in various physiological and pathological processes, particularly in the occurrence and progression of cancer. Numerous studies have indicated a close relationship between circRNAs and exosomes. Exosomal circRNAs (exo‑circRNAs) are a type of circRNA enriched in exosomes that may participate in the progression of cancer. Based on this, exo‑circRNAs may have an important role in malignant behavioral manifestations of cancer and hold great promise in the diagnosis and treatment of cancer. The present review gives an introduction to the origin and functions of exosomes and circRNAs and elaborates on the mechanisms of exo‑circRNAs in cancer progression. The biological functions of exo‑circRNAs in tumorigenesis, development and drug resistance, as well as their role as predictive biomarkers, were discussed.

Sevoflurane has become one of the most widely used volatile anesthetics in pediatric surgery. However, sevoflurane exposure may interfere with dendritic development and synaptogenesis, resulting in brain function impairment. The PI3K/AKT/mTOR pathway plays an important role in dendritic development and synaptic plasticity. Here we investigated whether sevoflurane exposure would affect the morphological proportions of dendritic spines in developing mouse and explored the role of the change of plasticity of dendritic spines in sevoflurane-induced neurodevelopmental toxicity. The related signaling pathway was also examined. C57BL/6 mice at postnatal day (PND) 7 were exposed to 2% sevoflurane for 3 h. The PI3k/AKT/mTOR agonist IGF-1 or the mTOR phosphorylation inhibitor KU0063794 was intraperitoneally injected 30 min before sevoflurane or O 2 exposure at PND7. Hippocampi were harvested 6 h after sevoflurane exposure. Western blotting was applied to measure the protein expression of PI3K/AKT/mTOR pathway phosphorylation. At PND14, brains from all groups were harvested for Golgi staining, and the morphology of dendritic spines of hippocampal neurons was observed by an oil immersion lens. When the mice grew to adolescence (PND48), fine motor function was measured by the Beam walking test. Here we showed that exposure to 2% sevoflurane for 3 h decreased the proportion of thin dendritic spines and increased the proportion of mushroom dendritic spines, but not changed the density of the dendritic spines. Sevoflurane exposure also suppressed the phosphorylation of the PI3K/AKT/mTOR pathway in immature mice hippocampi, and eventually led to long-term fine motor dysfunction. Meanwhile, IGF-1 pretreatment could rescue and KU0063794 pretreatment could aggravate the impairment induced by sevoflurane. In conclusion, sevoflurane exposure may cause a change of proportions of the types of dendritic spines through impacting the phosphorylation expression of the PI3K/AKT/mTOR pathway, and eventually led to long-term fine motor dysfunction in developing mouse., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhong, Ma, Niu, Zhang, Xue, Yan and Jiang.)

Colon adenocarcinoma (COAD) is a prevalent malignant tumor that severely threatens human health across the globe. Immunotherapy is an essential need for patients with COAD. N7-methylguanosine (m7G) has been associated with human diseases, and non-coding RNAs (lncRNAs) regulate various tumor-related biological processes. Nonetheless, the m7G-related lncRNAs involved in COAD regulation are limited. This study aims to construct the clustering features and prognostic model of m7G-related lncRNAs in COAD. First, The Cancer Genome Atlas (TCGA) database was used to identify m7G-related differentially expressed lncRNAs (DELs), based on which COAD cases could be classified into two subtypes. Subsequently, univariate Cox analysis was used to identify 9 prognostic m7G-related lncRNAs. Further, Five candidates were screened by LASSO-Cox regression to develop new models. The patients were divided into high-risk and low-risk groups based on the median risk score. Consequently, the Kaplan-Meier survival curve demonstrated a statistically significant overall survival (OS) between the high- and low-risk groups (P<0.001). Multivariate Cox regression analysis revealed that risk score is an independent prognostic factor in COAD patients (P<0.001). This confirms the clinical applicability of the model. Additionally, we performed Gene Set Enrichment Analysis (GSEA), which uncovered the biological and functional differences between risk subgroups, i.e., enrichment of immune-related diseases in the high-risk group and enrichment of metabolic-related pathways in the low-risk group. In a drug sensitivity analysis, high-risk group were more sensitive to some chemotherapeutics and targeted drugs than low-risk group. Eventually, the stability of the model was confirmed by qRT-PCR. Our study unraveled the features of different immune states of COAD and established a prognostic model, including five m7G-related lncRNAs for COAD patients. These results will bolster clinical treatment and survival prediction of COAD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cheng, Wang, Xu, Jiang, Xue, Li, Zhao, Song and Song.)

Objective: In the lipid-rich brain, lipids performed signaling processes associated with the control system of the cell cycle, stress, and inflammatory reactions, as well as maintained brain and cellular homeostasis. The effects of general anesthesia on brain impairment in the elderly were controversial and complex. The study sought to evaluate the effect of lipid metabolism in the brain of aged marmosets and mice under long-term exposure to sevoflurane., Methods: A total of 6 marmosets over 8-year-old and 10 mice aged 18 months were divided into the sevoflurane anesthesia and control groups, respectively. Marmosets in the sevoflurane anesthesia group were exposed to 1.5-2.5% sevoflurane and 100% O 2 for 6 h. Mice anesthetized with sevoflurane were exposed to 3% sevoflurane and 60% O 2 for 6 h. All prefrontal cortex tissues of marmosets and mice were harvested for the analysis of lipidomics., Results: Compared to the control group, we found that phosphatidylethanolamine (PE) (18:0/22:5), PE (16:0/22:5), PE (18:2/22:5), PE (14:0/22:5), and PE (18:1/22:5) increased in the prefrontal cortex of marmosets in the sevoflurane group, while triglyceride (TAG)56:5-fatty acid (FA) 20:4, TAG58:10-FA22:6, and TAG60:10-FA22:6 decreased. For aged mice, we indicated that lipid components phosphatidic acid (PA) (18:1/20:2) and TAG52:5-FA20:4 in the sevoflurane group increased, but PE (14:0/22:4), diglyceride (DAG) (16:1/18:2), and lysophosphatidylcholine (LPC) (16:1) + AcO decreased. More deeply, sevoflurane anesthesia resulted in the presence of 70 specific lipids in mice and marmosets. The enriched lipid subclasses were mainly monoacylglycerophosphoethanolamines and five other subclasses., Conclusion: Sevoflurane caused slight changes in lipid metabolism both in the aged brain of marmosets and mice. However, the pathways of lipid metabolism were not affected. The effects of sevoflurane on lipid metabolism in aged brains may differ among species., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mao, Zhu, Cheng, Shi, Chen, Zhou, Xue, Liu, Qiu and Jiang.)

Background: Surgery under general anesthesia leads to neural injury, especially in older patients. Sevoflurane anesthesia without surgery for 2 h does not induce neural injury, however, whether prolonger sevoflurane anesthesia without surgery has the same consequence is still unknown., Methods: In the present study, aged marmosets were exposed to a clinical concentration of sevoflurane (1.5-2%) for 6 h to access the effects of prolonged sevoflurane anesthesia on the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), Caspase3 activity and myelin formation in the brain., Results: Sevoflurane anesthesia did not alter the expression of IL-6 (120.1 ± 2.21 vs. 120.8 ± 2.25, p = 0.74), TNF-α (189.3 ± 31.35 vs. 218.7 ± 21.47, p = 0.25) and Caspase3 (57.35 ± 1.54 vs. 58.67 ± 1.19, p = 0.53) in the prefrontal cortex (PFC) of aged marmosets. The amount of MBP expression (60.99 ± 6.21 vs. 58.91 ± 2.71, p = 0.77) did not change following sevoflurane exposure., Conclusion: Sevoflurane anesthesia did not increase the levels of IL-6 and TNF-α, activated the the expression of Caspase3, and induced myelination deficits in the PFC of aged marmosets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cheng, Shi, Mao, Xue, Liu, Qiu, Zhang and Jiang.)

Clinical surgical practices have found that children who undergo multiple anesthesia may have an increased risk of deficiencies in cognition and fine motor control. Here, we report that YT521-B homology domain family 1 (YTHDF1), a critical reader protein for N6-methyladenosine-modified mRNA, was significantly downregulated in the prefrontal cortex of young mice after multiple sevoflurane anesthesia exposures. Importantly, sevoflurane led to a decrease in protein synthesis in mouse cortical neurons that was fully rescued by YTHDF1, suggesting that anesthesia may affect early brain development by affecting m6A-dependent mRNA translation. Transcriptome-wide experiments showed that numerous mRNA targets related to synaptic functions in the prefrontal mouse cortex were associated with m6A methylation and YTHDF1. In particular, we found that synaptophysin, a critical presynaptic protein, was specifically modified by m6A methylation and associated with YTHDF1, and m6A methylation of synaptophysin decreased with multiple sevoflurane exposures. Importantly, we showed that fine motor control skills and cognitive functions were impaired in mice with multiple anesthesia exposures, and these effects were fully reversed by reintroducing YTHDF1 through a blood-brain barrier (BBB)-crossing viral delivery system. Finally, we found that the fine motor skills in children who underwent prolonged anesthesia were compromised 6 months after surgery. Our findings indicated that impairment in the translational regulation of mRNA via N6-methyladenosine methylation is a potential mechanism underlying the effects of anesthesia on neural development in the young brain. 1. N6-methyladenosine (m6A) modifications were involved in anesthesia-induced neurotoxicity. 2. Sevoflurane impairs m6A-mediated mRNA translation and leads to fine motor deficits in young mice. 3. YTHDF1, a m6A reader protein, rescued sevoflurane-induced protein synthesis inhibition and fine motor deficits in young mice., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Clinical investigations to date have proposed the possibility that exposure to anesthetics is associated with neurodevelopmental deficits. Sevoflurane is the most commonly used general anesthetic in pediatric patients. Animal studies have demonstrated that multiple exposures to sevoflurane during the postnatal period resulted in neuropathological brain changes and long-term cognitive deficits. However, the underlying mechanisms remain to be clarified. In this study, methylated RNA immunoprecipitation sequencing (MeRIP-Seq) was performed to acquire genome-wide profiling of RNA N6-methyladenosine (m 6 A) in the prefrontal cortex of infant rhesus macaques. The macaques in the sevoflurane group had more m 6 A peaks than the macaques in the control group (p ≤ 0.05). After sevoflurane treatment, the mRNA levels of YT521-B homology domain family 1 (YTHDF1) and YT521-B homology domain family 3 (YTHDF3) were decreased, and sevoflurane anesthesia dynamically regulated RNA m 6 A methylation. Gene ontology (GO) analysis revealed that after sevoflurane exposure, genes with increased methylation of m 6 A sites were enriched in some physiological processes relevant to neurodevelopment, mainly focused on synaptic plasticity. The female macaques had 18 hypermethylated genes. The males had 35 hypermethylated genes, and some physiological processes related to the regulation of synaptic structure were enriched. Rhesus macaques are genetically closer to human beings. Our findings can help in the study of the mechanism of sevoflurane-relevant neurodevelopmental deficits at the posttranscriptional level and can provide new insights into potential clinical preventions and interventions for the neurotoxicity of neonatal anesthesia exposure., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Conflict of interest The authors declare that they have no conflict of interest.

Background: The anesthetics inhibit neural differentiation, induce neuron loss and cognitive impairment in young animals. However, the underlying mechanisms of anesthesia on neural differentiation are unknown. Methods: Embryonic stem cells (ESCs) and mice received sevoflurane anesthesia. RNA sequencing; gene expression of mRNAs, LncRNAs and miRNAs; over-expression and RNA interference of genes; flow cytometry; real-time quantity PCR and Western blot were used in the studies. RNA pull-down assay and PCR were employed to detect any miRNA that attached to Rik-203. The binding of miRNA with mRNA of BDNF was presented by the luciferase assay. Results: Here we found that LncRNA Riken-203(Rik-203) was highly expressed in mice brain and was upregulated during neural differentiation. Sevoflurane decreased the amount of Rik-203 in mice brain. Knockdown of Rik-203 repressed the neural differentiation derived from mouse embryonic stem cell and downregulated the neural progenitor cells markers Sox1 and Nestin. RNA pull-down showed that miR-466l-3p was highly bound to Rik-203. Inhibition of miR-466l-3p restored the neural differentiation repressed by Rik-203 knockdown. Brain derived neurotrophic factor (BDNF), which was downregulated by sevoflurane, was also directly targeted by miR-466l-3p. Overexpression of BDNF restored the neural differentiation repressed by miR-466l-3p and Rik-203 knockdown. Conclusion: Our study suggested that sevoflurane related LncRNARik-203 facilitates neural differentiation by inhibiting miR-466l-3p's ability to reduce BDNF levels., (Copyright © 2020 Zhang, Xue, Yan and Jiang.)

Objectives: Long non-coding RNAs (LncRNAs) play important roles in epigenetic regulatory function during the development processes. In this study, we found that through alternative splicing, LncRNA C130071C03Riken variants Riken-201 (Riken-201) and Riken-203 (Riken-203) are both expressed highly in brain, and increase gradually during neural differentiation. However, the function of Rik-201 and Rik-203 is unknown., Materials and Methods: Embryonic stem cells (ESCs); RNA sequencing; gene expression of mRNAs, LncRNAs and miRNAs; over-expression and RNA interference of genes; flow cytometry; real-time quantity PCR; and Western blot were used in the studies. RNA pull-down assay and PCR were employed to detect any miRNA that attached to Rik-201 and Rik-203. The binding of miRNA with mRNA of Sox6 was presented by the luciferase assay., Results: Repression of Rik-201 and Rik-203 inhibited neural differentiation from mouse embryonic stem cells. Moreover, Rik-201 and Rik-203 functioned as the competing endogenous RNA (ceRNA) to repress the function of miR-96 and miR-467a-3p, respectively, and modulate the expression of Sox6 to further regulate neural differentiation. Knockout of the Rik-203 and Rik-201 induced high ratio of brain developmental retardation. Further we found that C/EBPβ might potentially activated the transcription of Rik-201 and Rik-203., Conclusions: These findings identify the functional role of Rik-201 and Rik-203 in facilitating neural differentiation and further brain development, and elucidate the underlying miRNAs-Sox6-associated molecular mechanisms., (© 2019 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.)

Background: Exposure to anesthetics during early life may impair cognitive functions. However, the underlying mechanisms remain largely unknown. We set out to determine effects of sevoflurane anesthesia on folate metabolism and myelination in young non-human primates, mice and children., Methods: Young rhesus macaque and mice received 2.5 to 3% sevoflurane daily for three days. DNA and RNA sequencing and immunohistochemistry among others were used in the studies. We performed unbiased transcriptome profiling in prefrontal cortex of rhesus macaques and mice after the sevoflurane anesthesia. We constructed a brain blood barrier-crossing AAV-PHP.EB vector to harbor ERMN expression in rescue studies. We measured blood folate levels in children after anesthesia and surgery., Findings: We found that thymidylate synthase (TYMS) gene was downregulated after the sevoflurane anesthesia in both rhesus macaque and mice. There was a reduction in blood folate levels in children after the anesthesia and surgery. Combined with transcriptome and genome-wide DNA methylation analysis, we identified that ERMN was the primary target of the disrupted folate metabolism. Myelination was compromised by the anesthesia in the young mice, which was rescued by systematic administration of folic acid or expression of ERMN in the brain through brain-specific delivery of the adeno-associated virus. Moreover, folic acid and expression of ERMN alleviated the cognitive impairment caused by the sevoflurane anesthesia in the mice., Interpretation: General anesthesia leads to disrupted folate metabolism and subsequently defects in myelination in the developmental brain, and ERMN is the important target affected by the anesthesia via epigenetic mechanisms., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Targeting Bcl-2 with ABT-199 (Venetoclax) shows limited single-agent activity against many cancers in both preclinical and clinical investigations. Combination therapies have attracted great attention. The principal purpose of this study was to investigate the mechanism of synergism between ABT-199 and paclitaxel. Moreover, we analyzed the biomarker to identify tumors which are most likely to respond to this combination. We evaluated the effect of this combination in a panel of nine cancer cell lines including cervical cancer, lung cancer, ovarian cancer, lymphoma, leukemia and breast cancer. Combination index (CI) assay showed that four of nine call lines exhibited synergistic respond to ABT-199/paclitaxel combination due to enhanced intrinsic apoptosis. However, paclitaxel-induced Bcl-2 phosphorylation impaired the synergistic effect by impeding the freeing of Bax and Bim by ABT-199 because ABT-199 cannot hit phosphorylated Bcl-2 (pBcl-2). By means of a correlation analysis of JNK level with CI value in combination with overexpressing or silencing JNK protein in cancer cells, we identified basal JNK1 level as a potential biomarker for predicting the level of pBcl-2 upon paclitaxel treatment, and thus for predicting a synergistic response. A cut-off value of 0.37 for relative JNK1 expression level was determined using receiver operating characteristic (ROC) analysis to distinguish between synergistic and non-synergistic response cancers. A more accurate and valid cut-off value for JNK1 will be gained based on a large-scale clinical samples analysis., (Copyright © 2018 Elsevier Inc. All rights reserved.)