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1.
Mol Psychiatry ; 28(1): 17-27, 2023 01.
Article in English | MEDLINE | ID: mdl-35790874

ABSTRACT

Individual differences in human brain structure, function, and behavior can be attributed to genetic variations, environmental exposures, and their interactions. Although genome-wide association studies have identified many genetic variants associated with brain imaging phenotypes, environmental exposures associated with these phenotypes remain largely unknown. Here, we propose that environmental neuroscience should pay more attention on exploring the associations between lifetime environmental exposures (exposome) and brain imaging phenotypes and identifying both cumulative environmental effects and their vulnerable age windows during the life course. Exposome-neuroimaging association studies face several challenges including the accurate measurement of the totality of environmental exposures varied in space and time, the highly correlated structure of the exposome, and the lack of standardized approaches for exposome-wide association studies. By agnostically scanning the effects of environmental exposures on brain imaging phenotypes and their interactions with genomic variations, exposome-neuroimaging association analyses will improve our understanding of causal factors associated with individual differences in brain structure and function as well as their relations with cognitive abilities and neuropsychiatric disorders.


Subject(s)
Exposome , Humans , Genome-Wide Association Study , Environmental Exposure/adverse effects , Brain , Cognition
2.
Mol Psychiatry ; 28(11): 4853-4866, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37737484

ABSTRACT

Exposure to preadult environmental exposures may have long-lasting effects on mental health by affecting the maturation of the brain and personality, two traits that interact throughout the developmental process. However, environment-brain-personality covariation patterns and their mediation relationships remain unclear. In 4297 healthy participants (aged 18-30 years), we combined sparse multiple canonical correlation analysis with independent component analysis to identify the three-way covariation patterns of 59 preadult environmental exposures, 760 adult brain imaging phenotypes, and five personality traits, and found two robust environment-brain-personality covariation models with sex specificity. One model linked greater stress and less support to weaker functional connectivity and activity in the default mode network, stronger activity in subcortical nuclei, greater thickness and volume in the occipital, parietal and temporal cortices, and lower agreeableness, consciousness and extraversion as well as higher neuroticism. The other model linked higher urbanicity and better socioeconomic status to stronger functional connectivity and activity in the sensorimotor network, smaller volume and surface area and weaker functional connectivity and activity in the medial prefrontal cortex, lower white matter integrity, and higher openness to experience. We also conducted mediation analyses to explore the potential bidirectional mediation relationships between adult brain imaging phenotypes and personality traits with the influence of preadult environmental exposures and found both environment-brain-personality and environment-personality-brain pathways. We finally performed moderated mediation analyses to test the potential interactions between macro- and microenvironmental exposures and found that one category of exposure moderated the mediation pathways of another category of exposure. These results improve our understanding of the effects of preadult environmental exposures on the adult brain and personality traits and may facilitate the design of targeted interventions to improve mental health by reducing the impact of adverse environmental exposures.


Subject(s)
Brain , Personality , Adult , Humans , Neuroticism , Brain Mapping , Environmental Exposure
3.
J Org Chem ; 89(4): 2375-2396, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38288704

ABSTRACT

A universal glycosylation strategy could significantly simplify glycoside synthesis. One approach to achieving this goal is through acyl group direction for the corresponding 1,2-, 1,3-, 1,4-, or 1,6-trans glycosylation; however, this approach has been challenging for glycosidic bonds that require distal equatorial-acyl group direction. We developed an approach in weakly nucleophilic environments for selective 1,4-trans glycosylation directed by the equatorial-4-O-acyl group. Here, we explored this condition in other distal acyl groups and found that, besides 1,n-trans direction, acyl groups also mediated hydrogen bonding between acyl groups and alcohols. The latter showed a diverse effect and classified the acyl group direction into axial and equatorial categories. Corresponding glycosylation conditions were distinguished as guidance for acyl group direction from either category. Hence, acyl group direction may serve as a general glycosylation strategy.

4.
Cereb Cortex ; 33(12): 8035-8045, 2023 06 08.
Article in English | MEDLINE | ID: mdl-36935097

ABSTRACT

Evidence highlights that dopamine (DA) system dysregulation and prefrontal cortex (PFC) dysfunction may underlie the pathophysiology of schizophrenia. However, the associations among DA genes, PFC morphometry, and schizophrenia have not yet been fully clarified. Based on the brain gene expression dataset from Allen Human Brain Atlas and structural magnetic resonance imaging data (NDIS = 1727, NREP = 408), we first identified 10 out of 22 PFC subregions whose gray matter volume (GMV) covariance profiles were reliably associated with their DA genes coexpression profiles, then four out of the identified 10 PFC subregions demonstrated abnormally increased GMV covariance with the hippocampus, insula, and medial frontal areas in schizophrenia patients (NCASE = 100; NCONTROL = 102). Moreover, based on a schizophrenia postmortem expression dataset, we found that the DA genes coexpression of schizophrenia was significantly reduced between the middle frontal gyrus and hippocampus, in which 21 DA genes showed significantly unsynchronized expression changes, and the 21 genes' brain expression were enriched in brain activity invoked by working memory, reward, speech production, and episodic memory. Our findings indicate the DA genes selectively regulate the structural covariance of PFC subregions by their coexpression profiles, which may underlie the disrupted GMV covariance and impaired cognitive functions in schizophrenia.


Subject(s)
Dopamine , Gene Expression Regulation , Gray Matter , Prefrontal Cortex , Schizophrenia , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/metabolism , Schizophrenia/diagnostic imaging , Schizophrenia/genetics , Schizophrenia/metabolism , Dopamine/metabolism , Gray Matter/diagnostic imaging , Gray Matter/metabolism , Memory, Short-Term , Memory, Episodic , Reward , Speech , Humans , Male , Female , Adolescent , Young Adult , Adult , Datasets as Topic , Magnetic Resonance Imaging
5.
PLoS Genet ; 17(2): e1009363, 2021 02.
Article in English | MEDLINE | ID: mdl-33630843

ABSTRACT

Genome-wide association studies (GWASs) have identified multiple susceptibility loci for Alzheimer's disease (AD), which is characterized by early and progressive damage to the hippocampus. However, the association of hippocampal gene expression with AD and the underlying neurobiological pathways remain largely unknown. Based on the genomic and transcriptomic data of 111 hippocampal samples and the summary data of two large-scale meta-analyses of GWASs, a transcriptome-wide association study (TWAS) was performed to identify genes with significant associations between hippocampal expression and AD. We identified 54 significantly associated genes using an AD-GWAS meta-analysis of 455,258 individuals; 36 of the genes were confirmed in another AD-GWAS meta-analysis of 63,926 individuals. Fine-mapping models further prioritized 24 AD-related genes whose effects on AD were mediated by hippocampal expression, including APOE and two novel genes (PTPN9 and PCDHA4). These genes are functionally related to amyloid-beta formation, phosphorylation/dephosphorylation, neuronal apoptosis, neurogenesis and telomerase-related processes. By integrating the predicted hippocampal expression and neuroimaging data, we found that the hippocampal expression of QPCTL and ERCC2 showed significant difference between AD patients and cognitively normal elderly individuals as well as correlated with hippocampal volume. Mediation analysis further demonstrated that hippocampal volume mediated the effect of hippocampal gene expression (QPCTL and ERCC2) on AD. This study identifies two novel genes associated with AD by integrating hippocampal gene expression and genome-wide association data and reveals candidate hippocampus-mediated neurobiological pathways from gene expression to AD.


Subject(s)
Alzheimer Disease/genetics , Genetic Predisposition to Disease/genetics , Genome-Wide Association Study/methods , Hippocampus/metabolism , Polymorphism, Single Nucleotide , Transcriptome/genetics , Aged , Aged, 80 and over , Alzheimer Disease/diagnostic imaging , Female , Gene Regulatory Networks/genetics , Genomics/methods , Hippocampus/diagnostic imaging , Humans , Magnetic Resonance Imaging/methods , Male , Whole Genome Sequencing/methods
6.
Int J Mol Sci ; 25(2)2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38255774

ABSTRACT

Variability in food availability leads to condition-dependent investments in reproduction. This study is aimed at understanding the metabolic response and regulatory mechanism of female Scylla paramamosain in response to starvation in a temporal- and tissue-specific manner. The mud crabs were starved for 7 (control), 14, 28, and 40 days for histological and biochemical analysis in the hepatopancreas, ovary, and serum, as well as for RNA sequencing on the hepatopancreas and ovary. We further highlighted candidate gene modules highly linked to physiological traits. Collectively, our observations suggested that starvation triggered endogenous ovarian maturation at the expense of hepatopancreas mass, with both metabolic adjustments to optimize energy and fatty acid supply from hepatopancreas to ovary in the early phase, followed by the activation of autophagy-related pathways in both organs over prolonged starvation. These specific adaptive responses might be considered efficient strategies to stimulate ovarian maturation of Scylla paramamosain under fasting stress, which improves the nutritional value of female mud crabs and other economically important crustaceans.


Subject(s)
Brachyura , Starvation , Female , Animals , Brachyura/genetics , Transcriptome , Starvation/genetics , Fasting , Autophagy
7.
J Perianesth Nurs ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980239

ABSTRACT

PURPOSE: To study the analgesic effects and side effects of a transdermal lappaconitine (TLA) patch, ibuprofen suspension (IS), and TLA combined with IS (TLACIS) after adenoidectomy and tonsillectomy. DESIGN: Prospective, randomized clinical trial. METHODS: The patients were randomized into three groups defined by different analgesic drug regimens: the TLA group, the IS group, and the TLACIS group. Pain scores at 2, 12, and 24 hours after surgery and adverse-event reports within the first postoperative week were collected. RESULTS: Ultimately, this study included 102 cases in the TLA group, 101 cases in the IS group, and 101 cases in the TLACIS group. At 2 hours after surgery, the pain scores of the TLA and the TLACIS groups were both significantly lower than that of the IS group (all P < .05). At 12 and 24 hours after surgery, the pain score of the TLACIS group was significantly lower than those of the TLA and IS groups (all P < .05); furthermore, the pain score of the IS group was significantly lower than that of the TLA group (P < .05). Within 1 week after the operation, there was no significant difference in the incidence of adverse events. CONCLUSIONS: The addition of a TLA patch can speed the onset of analgesia. In terms of analgesic effects, IS alone is more advantageous than TLA alone, while the combination of TLA and IS has the best analgesic effect. No significant differences were found in the incidence of adverse events among the three regimens.

8.
J Cell Physiol ; 238(3): 659-669, 2023 03.
Article in English | MEDLINE | ID: mdl-36780378

ABSTRACT

Hepatic ischemia-reperfusion (I/R) injury commonly occurs during liver surgery. Exosomes from adipose-derived stem cells (ADSCs-exo) induce a hepatoprotective effect during hepatic I/R injury. This study aimed to investigate the possible mechanism by which ADSCs-exo attenuates hepatic I/R injury in rats. Rats were randomly divided into four groups: Sham, I30R + PH, ADSCs, and ADSCs-exo groups. Liver tissues were collected immediately after 24 h of reperfusion for further analyses. The content of inflammatory factors in liver tissue was detected using enzyme-linked immunosorbent assay. The pathological changes in liver tissue were analyzed using HE staining. Transmission electron microscopy was used to visualize the ultrastructural changes of hepatocytes. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were used to detect the expression of endoplasmic reticulum stress (ERS)-related genes and proteins. Liver histomorphology and hepatocyte ultrastructure changes improved after ADSCs-exo treatment. Moreover, ADSCs-exo treatment significantly downregulated tumor necrosis factor-α, interleukin-1ß (IL-1ß), and IL-6 levels while upregulating IL-10 levels. Western blot analysis suggested that the protein expressions of GRP78, p-PERK, p-eIF2α, p-IRE1α, XBP1s, ATF-6, ATF-4, CHOP, p-JNK, cleaved-Caspase-3, cleaved Caspase-9, and cleaved Caspase-12 significantly decreased after ADSCs-exo treatment. RT-qPCR results demonstrated that mRNA expression of GRP78, IRE1α, XBP1, ATF-6, ATF-4, CHOP, JNK, Caspase-3, Caspase-9, and Caspase-12 markedly reduced after ADSCs-exo treatment. In conclusion, ADSCs-exo protects against hepatic I/R injury after hepatectomy by inhibiting ERS and inflammation. Therefore, ADSCs-exo can be considered as a viable option for the treatment of hepatic I/R injury.


Subject(s)
Adipose Tissue , Endoplasmic Reticulum Stress , Exosomes , Hepatectomy , Inflammation , Liver , Reperfusion Injury , Stem Cells , Animals , Rats , Inflammation/pathology , Inflammation/prevention & control , Liver/metabolism , Liver/pathology , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Exosomes/metabolism , Stem Cells/metabolism , Adipose Tissue/cytology , Caspases/metabolism , Interleukins/metabolism
9.
Mol Psychiatry ; 27(11): 4432-4445, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36195640

ABSTRACT

Human hippocampal volume has been separately associated with single nucleotide polymorphisms (SNPs), DNA methylation and gene expression, but their causal relationships remain largely unknown. Here, we aimed at identifying the causal relationships of SNPs, DNA methylation, and gene expression that are associated with hippocampal volume by integrating cross-omics analyses with genome editing, overexpression and causality inference. Based on structural neuroimaging data and blood-derived genome, transcriptome and methylome data, we prioritized a possibly causal association across multiple molecular phenotypes: rs1053218 mutation leads to cg26741686 hypermethylation, thus leads to overactivation of the associated ANKRD37 gene expression in blood, a gene involving hypoxia, which may result in the reduction of human hippocampal volume. The possibly causal relationships from rs1053218 to cg26741686 methylation to ANKRD37 expression obtained from peripheral blood were replicated in human hippocampal tissue. To confirm causality, we performed CRISPR-based genome and epigenome-editing of rs1053218 homologous alleles and cg26741686 methylation in mouse neural stem cell differentiation models, and overexpressed ANKRD37 in mouse hippocampus. These in-vitro and in-vivo experiments confirmed that rs1053218 mutation caused cg26741686 hypermethylation and ANKRD37 overexpression, and cg26741686 hypermethylation favored ANKRD37 overexpression, and ANKRD37 overexpression reduced hippocampal volume. The pairwise relationships of rs1053218 with hippocampal volume, rs1053218 with cg26741686 methylation, cg26741686 methylation with ANKRD37 expression, and ANKRD37 expression with hippocampal volume could be replicated in an independent healthy young (n = 443) dataset and observed in elderly people (n = 194), and were more significant in patients with late-onset Alzheimer's disease (n = 76). This study revealed a novel causal molecular association mechanism of ANKRD37 with human hippocampal volume, which may facilitate the design of prevention and treatment strategies for hippocampal impairment.


Subject(s)
DNA Methylation , Hippocampus , Aged , Animals , Humans , Mice , Alleles , Alzheimer Disease/genetics , DNA Methylation/genetics , Epigenome , Hippocampus/metabolism , Polymorphism, Single Nucleotide/genetics
10.
Crit Rev Food Sci Nutr ; 62(25): 6887-6907, 2022.
Article in English | MEDLINE | ID: mdl-33830835

ABSTRACT

With the gradually increasing prevalence of food allergy in recent years, food allergy has become a major public health problem worldwide. The clinical symptoms caused by food allergy seriously affect people's quality of life; there are unknown allergen components in novel food and hidden allergens caused by cross contamination in food processing, which pose a serious risk to allergy sufferers. Thus, rapid and multiplex detection methods are required to achieve on-site detection or examination of allergic components, so as to identify the risk of allergy in time. This paper reviews the progress of high-efficiency detection of food allergens, including enhanced traditional detection techniques and emerging detection techniques with the ability high-throughput detection or screening potential food allergen, such as xMAP, biosensors, biochips, etc. focusing on their sensitivity, applicability of each method in food, along with their pretreatment, advantages, limitation in the application of food analysis. This paper also introduces the challenges faced by these high-efficiency detection technologies, as well as the potential of customized allergen screening methods and rapid on-site detection technology as future research directions.


Subject(s)
Food Hypersensitivity , Quality of Life , Allergens/analysis , Food , Food Analysis , Food Hypersensitivity/diagnosis , Food Hypersensitivity/etiology , Humans
11.
Cereb Cortex ; 31(2): 746-756, 2021 01 05.
Article in English | MEDLINE | ID: mdl-32710107

ABSTRACT

Much evidence indicates the influence of the oxytocin receptor (OXTR) gene on autism spectrum disorders (ASDs), a set of disorders characterized by a range of deficits in prosocial behaviors, which are closely related to the personality trait of reward dependence (RD). However, we do not know the effect of the OXTR polygenic risk score for ASDs (OXTR-PRSASDs) on RD and its underlying neuroanatomical substrate. Here, we aimed to investigate associations among the OXTR-PRSASDs, gray matter volume (GMV), and RD in two independent datasets of healthy young adults (n = 450 and 540). We found that the individuals with higher OXTR-PRSASDs had lower RD and significantly smaller GMV in the right posterior insula and putamen. The GMV of this region showed a positive correlation with RD and a mediation effect on the association between OXTR-PRSASDs and RD. Moreover, the correlation map between OXTR-PRSASDs and GMV showed spatial correlation with OXTR gene expression. All results were highly consistent between the two datasets. These findings highlight a possible neural pathway by which the common variants in the OXTR gene associated with ASDs may jointly impact the GMV of the right posterior insula and putamen and further affect the personality trait of RD.


Subject(s)
Autism Spectrum Disorder/genetics , Cerebral Cortex/physiopathology , Putamen/physiopathology , Receptors, Oxytocin/genetics , Reward , Adolescent , Adult , Brain Mapping , Female , Gene Frequency , Genetic Variation , Genotype , Gray Matter/diagnostic imaging , Humans , Male , Multifactorial Inheritance , Neural Pathways/physiopathology , Polymorphism, Single Nucleotide , Young Adult
12.
Cereb Cortex ; 31(4): 2268-2277, 2021 03 05.
Article in English | MEDLINE | ID: mdl-33270830

ABSTRACT

Although both the granular layer of the prefrontal cortex (PFC) and schizophrenia are unique in primates, especially humans, their linkage is unclear. Here, we tested whether schizophrenia is associated with expression profiles of the granule cell (GC)-related genes in the human PFC. We identified 14 candidate GC-related genes with gradually increased expression levels along the gradient of the agranular, dysgranular, light-granular, and granular prefrontal regions based on the densely sampled gene expression data of 6 postmortem human brains, and with more than 10-fold expression in neurons than other cell types based on the single-cell RNA-sequencing data of the human PFC. These GC-related genes were functionally associated with synaptic transmission and cell development and differentiation. The identified 14 GC-related genes were significantly enriched for schizophrenia, but not for depression and bipolar disorder. The expression levels of the 4 stable schizophrenia- and GC-related genes were spatially correlated with gray matter volume differences in the PFC between patients with schizophrenia and healthy controls. This study provides a set of candidate genes for the human prefrontal GCs and links expression profiles of the GC-related genes to the prefrontal structural impairments in schizophrenia.


Subject(s)
Databases, Genetic , Genetic Association Studies/methods , Prefrontal Cortex/diagnostic imaging , Schizophrenia/diagnostic imaging , Schizophrenia/genetics , Gene Expression Regulation , Humans , Magnetic Resonance Imaging/methods , Prefrontal Cortex/pathology , Schizophrenia/pathology
13.
Ecotoxicol Environ Saf ; 236: 113466, 2022 May 01.
Article in English | MEDLINE | ID: mdl-35390688

ABSTRACT

Zearalenone (ZEN), one of the most contaminated Fusarium toxins worldwide, is very common in contaminating wheat, corn oil and other foods. People are more vulnerable to ZEN exposure with more daily caloric intake, yet little is known about the combined effect of different dietary patterns with mycotoxins. This study aimed to compare the effects of long-term ZEN exposure on the overall biochemical landscape of the "gut-blood-liver axis" under normal diet and high-fat diet (HFD) using a combined multi-omics approach. The results indicated that ZEN exposure, possibly via the phenylalanine metabolic pathway, led to dysbiosis of mouse flora, suppression of short-chain fatty acids (SCFAS) metabolism, systemic inflammatory responses, and disturbances in serum and liver metabolism, which were exacerbated in synergy with HFD and ultimately led to a more severe state of lipid metabolism in the liver. We further found that ZEN exposure attenuated the indole-3-propionic acid (IPA) metabolic pathway, enhanced 2-hydroxybutyric acid metabolism in serum, and attenuated ß-alanine metabolism in liver which was positively correlated with the abundance of Prevotellaceae UCG-004, Prevotellaceae UCG-001, and Prevotellaceae NK3B31 groups. The results highlighted the damaging effects of ZEN on the gut-blood-liver axis under different dietary patterns, which might serve as a reference for future studies exploring the combined effects of fungal toxins and multiple dietary patterns.


Subject(s)
Mycotoxins , Trichothecenes , Zearalenone , Animals , Diet , Humans , Liver , Mice , Mycotoxins/metabolism , Zearalenone/toxicity
14.
J Cell Mol Med ; 25(21): 10152-10163, 2021 11.
Article in English | MEDLINE | ID: mdl-34609057

ABSTRACT

Hepatic ischaemia reperfusion injury (HIRI) is a major factor leading to liver dysfunction after liver resection and liver transplantation. Adipose-derived mesenchymal stem cells (ADSCs) have potential therapeutic effects on HIRI. Exosomes derived from ADSCs (ADSCs-exo) have been widely studied as an alternative of ADSCs therapy. Thus, the aim of this study was to evaluate the potential protective effect and related mechanism of ADSCs-exo on HIRI subsequent to hepatectomy. Rats were randomly divided into four groups: Sham, I30R+PH, ADSCs and ADSCs-exo group. After 24 h of reperfusion, liver and serum of the rats were immediately collected. ADSCs-exo improved liver function, inhibited oxidative stress and reduced apoptosis of hepatocytes in HIRI subsequent to hepatectomy in rats. ADSCs-exo significantly promoted the recovery of mitochondrial function, markedly increased the content of ATP in the liver tissue, and improved the ultrastructure of mitochondria in hepatocytes. Moreover, ADSCs-exo significantly increased the expression of OPA-1, MFN-1 and MFN-2 proteins related to mitochondrial fusion, while DRP-1 and Fis-1 mRNA and protein expression associated with mitochondrial fission were significantly decreased after the treatment with ADSCs-exo. In addition, ADSCs-exo significantly increased the expression of PGC-1α, NRF-1 and TFAM genes and proteins related to mitochondrial biogenesis. ADSCs-exo improves liver function induced by HIRI subsequent to hepatectomy in rats and maintains mitochondrial homeostasis by inhibiting mitochondrial fission, promoting mitochondrial fusion and promoting mitochondrial biogenesis. Therefore, ADSCs-exo may be considered as a potential promising alternative to ADSCs in the treatment of HIRI subsequent to hepatectomy.


Subject(s)
Exosomes/metabolism , Liver/blood supply , Liver/metabolism , Mesenchymal Stem Cells/metabolism , Mitochondrial Dynamics , Reperfusion Injury/etiology , Reperfusion Injury/metabolism , Adenosine Triphosphate/metabolism , Adipose Tissue/cytology , Animals , Apoptosis , Biomarkers , Hepatectomy , Hepatocytes/metabolism , Immunophenotyping , Liver/pathology , Liver Function Tests , Oxidative Stress , Rats , Reperfusion Injury/pathology
15.
Hum Brain Mapp ; 42(11): 3470-3480, 2021 08 01.
Article in English | MEDLINE | ID: mdl-33939221

ABSTRACT

Working memory is a basic human cognitive function. However, the genetic signatures and their biological pathway remain poorly understood. In the present study, we tried to clarify this issue by exploring the potential associations and pathways among genetic variants, brain morphometry and working memory performance. We first carried out association analyses between 2-back accuracy and 212 image-derived phenotypes from 1141 Human Connectome Project (HCP) subjects using a linear mixed model (LMM). We found a significantly positive correlation between the left cuneus volume and 2-back accuracy (T = 3.615, p = 3.150e-4, Cohen's d = 0.226, corrected using family-wise error [FWE] method). Based on the LMM-based genome-wide association study (GWAS) on the HCP dataset and UK Biobank 33 k GWAS summary statistics, we identified eight independent single nucleotide polymorphisms (SNPs) that were reliably associated with left cuneus volume in both UKB and HCP dataset. Within the eight SNPs, we found a negative correlation between the rs76119478 polymorphism and 2-back accuracy accuracy (T = -2.045, p = .041, Cohen's d = -0.129). Finally, an LMM-based mediation analysis elucidated a significant effect of left cuneus volume in mediating rs76119478 polymorphism on the 2-back accuracy (indirect effect = -0.007, 95% BCa CI = [-0.045, -0.003]). These results were also replicated in a subgroup of Caucasians in the HCP population. Further fine mapping demonstrated that rs76119478 maps on intergene CTD-2315A10.2 adjacent to protein-encoding gene DAAM1, and is significantly associated with L3HYPDH mRNA expression. Our study suggested this new variant rs76119478 may regulate the working memory through exerting influence on the left cuneus volume.


Subject(s)
Genome-Wide Association Study , Memory, Short-Term/physiology , Occipital Lobe/anatomy & histology , Adult , Datasets as Topic , Female , Gene Expression Regulation , Humans , Magnetic Resonance Imaging , Male , Occipital Lobe/diagnostic imaging , Polymorphism, Single Nucleotide , Young Adult
16.
J Org Chem ; 86(19): 13350-13359, 2021 Oct 01.
Article in English | MEDLINE | ID: mdl-34516112

ABSTRACT

A practical and scalable ortho-selective deuteration of aromatic aldehydes was accomplished by Pd-catalyzed hydrogen isotope exchange with deuterium oxide as an inexpensive deuterium source. The use of tert-leucine as a transient directing group facilitates the exchange, affording a wide range of ortho-deuterated aromatic aldehydes with deuterium incorporation up to 97%. The control experiments suggest that the addition of silver trifluoroacetate resists the unexpected reduction of Pd(II), while the theoretical study indicates a rapid reversible concerted metalation-deprotonation process.

17.
Eur Arch Otorhinolaryngol ; 278(4): 925-932, 2021 Apr.
Article in English | MEDLINE | ID: mdl-32648030

ABSTRACT

OBJECTIVE: This meta-analysis is aimed to review and analyze all available data of intraoperative and postoperative results of endoscopic and microscopic stapes surgery. METHODS: According to the PRISMA statements checklist, this systematic review and meta-analysis were designed. Data were extracted from public databases, such as PubMed, Cochrane, Web of Science, and more. The quality of studies was evaluated using the MINORS scale. Odds ratios (ORs) and 95% CIs were estimated for binary outcome data, while the mean differences and 95% CIs were estimated for continuous data. I2 and χ2 tests were used to quantify statistical heterogeneity. If more than ten studies were included in each analysis, funnel plot would be performed to analysis publication bias. RESULTS: Twelve studies with 620 patients were included in this meta-analysis. Primary outcomes collected in this meta-analysis included average postoperative auditory gain (APAG), postoperative air-bone gap (ABG), the rate of chorda tympani handling and bone curettage, which all showed a statistically significant difference in favor of endoscopy. While only secondary outcomes about postoperative pain and dysgeusia demonstrated a significantly reduced incidence. Furthermore, there was not any statistically significant difference on postoperative dizziness and average operative time between endoscopy and microscopy. CONCLUSION: Although there is a need for high-quality pooled data in the future, a consistently superior effect of the endoscopic group was still shown in terms of total effectiveness, when compared to the microscopic group. We have reasons to support the application of endoscopy in stapes surgery. The future of ESS, we believe, is blazing bright.


Subject(s)
Otosclerosis , Stapes Surgery , Endoscopy , Humans , Microscopy , Operative Time , Otosclerosis/surgery , Reference Standards , Retrospective Studies , Stapes , Treatment Outcome
18.
Neuroimage ; 222: 117283, 2020 11 15.
Article in English | MEDLINE | ID: mdl-32828928

ABSTRACT

Converging evidence from both human and animal studies has highlighted the pervasive role of the neuropeptide arginine vasopressin (AVP), which is mediated by arginine vasopressin receptor 1A (AVPR1A), in both social and nonsocial learning and memory. However, the effect of genetic variants in AVPR1A on verbal learning and memory is unknown. The hippocampus is a heterogeneous structure that consists of several anatomically and functionally distinct subfields, and it is the principal target structure for the memory-enhancing effect of AVP. We tested the hypothesis that genetic variants in the RS3 and RS1 repeat polymorphisms may influence verbal learning and memory performance evaluated by the California Verbal Learning Test-II (CVLT-II) by modulating the gray matter volume (GMV) and resting-state functional connectivity (rsFC) of whole hippocampus and its subfields in a large cohort of young healthy subjects (n = 1001). Using a short/long classification scheme for the repeat length of RS3 and RS1, we found that the individuals carrying more short alleles of RS3-RS1 haplotypes had poorer learning and memory performance compared to that of those carrying more long alleles. We also revealed that individuals carrying more short alleles exhibited a significantly smaller GMV in the left cornu ammonis (CA)2/3 and weaker rsFC of the left CA2/3-bilateral thalamic (primarily in medial prefrontal subfields) compared to those carrying more long alleles. Furthermore, multiple mediation analysis confirmed that these two hippocampal imaging measures jointly and fully mediated the relationship between the genetic variants in AVPR1A RS3-RS1 haplotypes and the individual differences in verbal learning and memory performance. Our results suggest that genetic variants in AVPR1A RS3-RS1 haplotypes may affect verbal learning and memory performance in part by modulating the left hippocampal CA2/3 structure and its rsFC with the thalamus.


Subject(s)
Learning/physiology , Memory/physiology , Receptors, Vasopressin/genetics , Adolescent , Adult , Female , Genotype , Hippocampus/physiology , Humans , Male , Polymorphism, Genetic/genetics , Promoter Regions, Genetic/genetics , Verbal Learning/physiology , Young Adult
19.
Am J Otolaryngol ; 41(6): 102571, 2020.
Article in English | MEDLINE | ID: mdl-32590256

ABSTRACT

Endoscope is an innovative method for otologists in middle ear surgery. Many previous studies have confirmed the safety and efficiency of the endoscopic technique, as a reliable therapeutic option with very low complication rates, clearly supporting the use of endoscopy in ear surgery. Auricular suppurative perichondritis secondary to exclusive endoscopic ear surgery for tympanoplasty is an extremely rare type of those without any previously reported cases. In this report, we describe the course of auricular suppurative perichondritis of a 55-year-old woman. The patient was ultimately healed through surgical debridement and postoperative dressing with no evidence of recurrence at two months follow-up. There were no auricle deformity or external auditory canal stenosis with six months following-up.


Subject(s)
Cartilage Diseases/etiology , Ear Cartilage , Endoscopy/adverse effects , Endoscopy/methods , Otologic Surgical Procedures/adverse effects , Otologic Surgical Procedures/methods , Periapical Abscess/etiology , Postoperative Complications/etiology , Tympanoplasty/adverse effects , Tympanoplasty/methods , Bandages , Cartilage Diseases/therapy , Debridement/methods , Female , Humans , Middle Aged , Periapical Abscess/therapy , Postoperative Complications/therapy , Treatment Outcome
20.
J Org Chem ; 84(7): 4473-4477, 2019 04 05.
Article in English | MEDLINE | ID: mdl-30882223

ABSTRACT

Heliaquanoid A (1), the first exo-2,4-linked Diels-Alder adduct between a pseudoguaianolide dienophile and a guaianolide diene, and heliaquanoids B-E (2-5), four new 2,4-linked Diels-Alder adducts between a xanthanolide dienophile and a guaianolide diene, were isolated from stems and leaves of Inula helianthus-aquatica. Their structures were determined by NMR spectroscopy, a modified Mosher's method, electronic circular dichroism, and X-ray diffraction analysis. Compounds 2 and 3 exhibited moderate cytotoxic activities against HL-60 cells with IC50 values of 7.5 and 4.9 µM, respectively.


Subject(s)
Inula/chemistry , Sesquiterpenes/chemistry , A549 Cells , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Crystallography, X-Ray , Dimerization , Drug Screening Assays, Antitumor , HL-60 Cells , Helianthus/chemistry , Humans , MCF-7 Cells , Models, Molecular , Nuclear Magnetic Resonance, Biomolecular , Sesquiterpenes/isolation & purification , Sesquiterpenes/pharmacology
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