High-fat diet consumption promotes adolescent neurobehavioral abnormalities and hippocampal structural alterations via microglial overactivation accompanied by an elevated serum free fatty acid concentration.

Mounting evidence suggests that high-fat diet (HFD) consumption increases the risk for depression, but the neurophysiological mechanisms involved remain to be elucidated. Here, we demonstrated that HFD feeding of C57BL/6J mice during the adolescent period (from 4 to 8 weeks of age) resulted in increased depression- and anxiety-like behaviors concurrent with changes in neuronal and myelin structure in the hippocampus. Additionally, we showed that hippocampal microglia in HFD-fed mice assumed a hyperactive state concomitant with increased PSD95-positive and myelin basic protein (MBP)-positive inclusions, implicating microglia in hippocampal structural alterations induced by HFD consumption. Along with increased levels of serum free fatty acids (FFAs), abnormal deposition of lipid droplets and increased levels of HIF-1α protein (a transcription factor that has been reported to facilitate cellular lipid accumulation) within hippocampal microglia were observed in HFD-fed mice. The use of minocycline, a pharmacological suppressor of microglial overactivation, effectively attenuated neurobehavioral abnormalities and hippocampal structural alterations but barely altered lipid droplet accumulation in the hippocampal microglia of HFD-fed mice. Coadministration of triacsin C abolished the increases in lipid droplet formation, phagocytic activity, and ROS levels in primary microglia treated with serum from HFD-fed mice. In conclusion, our studies demonstrate that the adverse influence of early-life HFD consumption on behavior and hippocampal structure is attributed at least in part to microglial overactivation that is accompanied by an elevated serum FFA concentration and microglial aberrations represent a potential preventive and therapeutic target for HFD-related emotional disorders.

Deep Reinforcement Learning for Solving Vehicle Routing Problems With Backhauls.

The vehicle routing problem with backhauls (VRPBs) is a challenging problem commonly studied in computer science and operations research. Featured by linehaul (or delivery) and backhaul (or pickup) customers, the VRPB has broad applications in real-world logistics. In this article, we propose a neural heuristic based on deep reinforcement learning (DRL) to solve the traditional and improved VRPB variants, with an encoder-decoder structured policy network trained to sequentially construct the routes for vehicles. Specifically, we first describe the VRPB based on a graph and cast the solution construction as a Markov decision process (MDP). Then, to identify the relationship among the nodes (i.e., linehaul and backhaul customers, and the depot), we design a two-stage attention-based encoder, including a self-attention and a heterogeneous attention for each stage, which could yield more informative representations of the nodes so as to deliver high-quality solutions. The evaluation on the two VRPB variants reveals that, our neural heuristic performs favorably against both the conventional and neural heuristic baselines on randomly generated instances and benchmark instances. Moreover, the trained policy network exhibits a desirable capability of generalization to various problem sizes and distributions.

Recent Advances in Graphene-Based Materials for Zinc-Ion Batteries.

Zinc-ion batteries (ZIBs) are a promising alternative for large-scale energy storage due to their advantages of environmental protection, low cost, and intrinsic safety. However, the utilization of their full potential is still hindered by the sluggish electrode reaction kinetics, poor structural stability, severe Zn dendrite growth, and narrow electrochemical stability window of the whole battery. Graphene-based materials with excellent physicochemical properties hold great promise for addressing the above challenges foe ZIBs. In this review, the energy storage mechanisms and challenges faced by ZIBs are first discussed. Key issues and recent progress in design strategies for graphene-based materials in optimizing the electrochemical performance of ZIBs (anode, cathode, electrolyte, separator and current collector) are then discussed. Finally, some potential challenges and future research directions of graphene-based materials in high-performance ZIBs are proposed for practical applications.

Recent development of manganese dioxide-based materials as zinc-ion battery cathode.

The development of advanced cathode materials for zinc-ion batteries (ZIBs) is a critical step in building large-scale green energy conversion and storage systems in the future. Manganese dioxide is one of the most well-studied cathode materials for zinc-ion batteries due to its wide range of crystal forms, cost-effectiveness, and well-established synthesis processes. This review describes the recent research progress of manganese dioxide-based ZIBs, and the reaction mechanism, electrochemical performance, and challenges of manganese dioxide-based ZIBs materials are systematically introduced. Optimization strategies for high-performance manganese dioxide-based materials for ZIBs with different crystal forms, nanostructures, morphologies, and compositions are discussed. Finally, the current challenges and future research directions of manganese dioxide-based cathodes in ZIBs are envisaged.

Water/Light Multiregulated Supramolecular Polypseudorotaxane Gel with Switchable Room-Temperature Phosphorescence.

Water/light regulated room-temperature phosphorescence (RTP) of polypseudorotaxane supramolecular gel is constructed by threading the poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (PEG-PPG-PEG) chain with the bromoaromatic aldehyde into mono-(6-ethylenediamine-6-deoxygenated)-ß-cyclodextrin (ECD) cavities and further assembling with negatively charged Laponite XLG (CNS) and diarylethene derivative (DAE) through electrostatic interaction. This hydrogel exhibits significant blue fluorescence emission; instead, after lyophilization to xerogel, the system exhibits both blue fluorescence and yellow RTP based on the rigid network structure of the xerogel, which restricts the vibration of the phosphor and suppresses the nonradiative relaxation process. Interestingly, the addition of excess ECDs to the gel system can enhance the RTP emission. Furthermore, the reversible luminescence behavior can be adjusted by the photoresponsive isomerism of DAE and humidity. This polypseudorotaxane supramolecular gel system provides a novel strategy for constructing tunable RTP materials.

Rapid Detection of SARS-CoV-2 in Clinical and Environmental Samples via a Resonant Cavity SERS Platform within 20 min.

The coronavirus disease 2019 (COVID-19) epidemic has given a warning that it is important to explore the rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in clinical specimens or environmental samples for public health strategies and future variants. The surface-enhanced Raman spectroscopy (SERS) technique was demonstrated to achieve this goal. However, the consistency of signals originating from the poor compatibility of virions with SERS hotspots remains a key scientific challenge for the practical applications of SERS. Herein, we develop a SERS platform for the ultrasensitive and rapid detection of SARS-CoV-2 antigen within 20 min by the combination of a highly consistent SERS substrate and a supervised deep learning algorithm. A V-shaped resonant cavity array (VRC) substrate was fabricated to trap SARS-CoV-2 virions in the periodic V cavity array and stimulate the integral SERS signal of the virus via a resonance coupling effect. Benefiting from the unique architecture of the VRC substrate, we were able to directly detect the SARS-CoV-2 virus with high sensitivity and high consistency. These excellent performances enabled us to identify five different kinds of SARS-CoV-2 variants and detect SARS-CoV-2 from clinical and environmental samples with high accuracies.

[Analysis of a Chinese pedigree affected with Meckel syndrome due to variants of TMEM67 gene].

OBJECTIVE: To explore the genetic etiology for a Chinese pedigree affected with Meckel syndrome. METHODS: A pedigree with a history of three consecutive adverse pregnancies which presented at the First Affiliated Hospital of Zhengzhou University on August 31, 2017 was selected as the study subject. Clinical data of the pedigree were collected. High-throughput sequencing was carried out to screen for variants of ciliopathy-related genes in the third fetus following induced abortion, and candidate variant was verified by Sanger sequencing. RESULTS: The first pregnancy of the couple had ended as spontaneous abortion, whilst the fetus of the second pregnancy was suspected for having ciliopathy, though no genetic testing was carried out following elected abortion. The fetus of the third pregnancy was suspected for having ciliopathy, and high-throughput sequencing and Sanger sequencing had shown that the fetus had harbored compound heterozygous variants of the TMEM67 gene, including c.978+1G>A from the father and c.1288G>C (p.D430H) from the mother. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.978+1G>A was classified as a pathogenic variant (PVS1+PM2_Supporting+PP5), whilst the newly discovered c.1288G>C (p.D430H) was classified as a likely pathogenic variant (PM2_Supporting+PM3+PM5+PP3). CONCLUSION: The c.978+1G>A and c.1288G>C (p.D430H) compound heterozygous variants of the TMEM67 gene probably underlay the three consecutive adverse pregnancies suspected for ciliopathy in this pedigree. The discovery of c.1288G>C (p.D430H) has also expanded the mutational spectrum of the TMEM67 gene.

Voluntary wheel exercise ameliorates cognitive impairment, hippocampal neurodegeneration and microglial abnormalities preceded by demyelination in a male mouse model of noise-induced hearing loss.

Acquired peripheral hearing loss (APHL) in midlife has been identified as the greatest modifiable risk factor for dementia; however, the pathophysiological neural mechanisms linking APHL with an increased risk of dementia remain to be elucidated. Here, in an adult male mouse model of noise-induced hearing loss (NIHL), one of the most common forms of APHL, we demonstrated accelerated age-related cognitive decline and hippocampal neurodegeneration during a 6-month follow-up period, accompanied by progressive hippocampal microglial aberrations preceded by immediate-onset transient elevation in serum glucocorticoids and delayed-onset sustained myelin disruption in the hippocampus. Pretreatment with the glucocorticoid receptor antagonist RU486 before stressful noise exposure partially mitigated the early activation of hippocampal microglia, which were present at 7 days post noise exposure (7DPN), but had no impact on later microglial aberrations, hippocampal neurodegeneration, or cognitive decline exhibited at 1 month post noise exposure (1MPN). One month of voluntary wheel exercise following noise exposure barely affected either the hearing threshold shift or hippocampal myelin changes but effectively countered cognitive impairment and the decline in hippocampal neurogenesis in NIHL mice at 1MPN, paralleled by the normalization of microglial morphology, which coincided with a reduction in microglial myelin inclusions and a restoration of microglial hypoxia-inducible factor-1α (HIF1α) expression. Our results indicated that accelerated cognitive deterioration and hippocampal neuroplastic decline following NIHL are most likely driven by the maladaptive response of hippocampal microglia to myelin damage secondary to hearing loss, and we also demonstrated the potential of voluntary physical exercise as a promising and cost-effective strategy to alleviate the detrimental impact of APHL on cognitive function and thus curtail the high and continuously increasing global burden of dementia. Furthermore, the findings of the present study highlight the contribution of myelin debris overload to microglial malfunction and identify the microglial HIF1α-related pathway as an attractive candidate for future comprehensive investigation to obtain a more definitive picture of the underlying mechanisms linking APHL and dementia.

Photocontrolled Reversibly Chiral-Ordered Assembly Based on Cucurbituril.

Chirality transfer and regulation, accompanied by morphology transformation, arouse widespread interest for application in materials and biological science. Here, a photocontrolled supramolecular chiral switch is fabricated from chiral diphenylalanine (l-Phe-l-Phe, FF) modified with naphthalene (2), achiral dithienylethene (DTE) photoswitch (1), and cucurbit[8]uril (CB[8]). Chirality transfer from the chiral FF moiety of 2 to a charge-transfer (CT) heterodimer consisting of achiral guest 1 and achiral naphthalene (NP) in 2 has been unprecedented achieved via the encapsulation of CB[8]. On the contrary, chirality transfer from chiral FF to NP cannot be conducted in only guest 2. Crucially, induced circular dichroism of the heterodimer can be further modulated by distinct light, attributing to reversible photoisomerization of the DTE. Meanwhile, topological nanostructures are changed from one-dimensional (1D) nanofibers to two-dimensional (2D) nanosheets in the orderly assembling process of the heterodimer, which further achieved reversible interconversion between 2D nanosheets and 1D nanorods with tunable-induced chirality stimulated by diverse light.

Effect of light intensity on negative air ion under phytotron control.

Negative air ion (NAI) is an important index for measuring air quality and has been widely recognized to be influenced by photosynthesis processes. However, vegetation type and light intensity are also known to impact NAI, contributing to significant uncertainties in the relationship between light and NAI. In this paper, we selected Pinus bungeana, Platycladus orientalis and Buxus sinica as research subjects and obtained their NAI, light intensity, and meteorological data through synchronous observation under the relatively stable condition of the phytotron. We analyzed the change characteristics of NAI and the difference of NAI production ability in needle and broadleaf vegetation under different light intensities. Finally, we determined the relationship and underlying mechanism governing light intensity and NAI using diverse tree species. The results showed that the influence of light on NAI was significant. In the environment without vegetation, the influence of different light intensities on NAI was not significant, and the mean NAI concentration was 310 ions·cm-3. Conversely, in the presence of vegetation, NAI showed a "single-peak" trend with increasing light intensity. The NAI concentration of the three tree species was significantly higher than under different light intensities when vegetation was not present. The NAI promoting ability of P. bungeana was the highest (675 ions·cm-3), followed by P. orientalis (478 ions·cm-3) and B. sinica (430 ions·cm-3), which increased by 117.5%, 53.9% and 38.6% compared to the environment without vegetation. The NAI growth rate was significantly different between needle and broadleaf vegetation based on the specific tridimensional green biomass. Additionally, the NAI growth rates of P. bungeana and P. orientalis were 647 and 295 ions·cm-3·m-3, respectively, which were 3.06 and 1.39 times that of B. sinica (211 ions·cm-3·m-3). The piecewise equation fitting effect of NAI and light intensity was better for different tree species, the determination coefficients (R2) of P. bungeana, P. orientalis and B. sinica were 0.926, 0.916 and 0.880, and the root mean square errors (RMSE) were 7.157, 6.008 and 5.389 ion·cm-3, respectively. Altogether, our study provides a theoretical basis as well as technical support for the construction of healthy vegetation stands, the selection of preferred tree species, and the optimization of vegetation models, and promotes air quality and the provision of ecosystem functions and services.

High-Fat Diet Consumption Induces Neurobehavioral Abnormalities and Neuronal Morphological Alterations Accompanied by Excessive Microglial Activation in the Medial Prefrontal Cortex in Adolescent Mice.

The association between a high-fat diet (HFD) consumption and emotional/cognitive disorders is widely documented. One distinctive feature of the prefrontal cortex (PFC), a kernel emotion- and cognition-related brain region, is its protracted adolescent maturation, which makes it highly vulnerable to the detrimental effects of environmental factors during adolescence. Disruption of the PFC structure and function is linked to emotional/cognitive disorders, especially those that emerge in late adolescence. A HFD consumption is common among adolescents, yet its potential effects on PFC-related neurobehavior in late adolescence and any related underlying mechanisms are yet to be established. In the present study, adolescent (postnatal days 28-56) male C57BL/6J mice were fed a control diet (CD) or a HFD and underwent behavioral tests in addition to Golgi staining and immunofluorescence targeting of the medial PFC (mPFC). The HFD-fed adolescent mice exhibited anxiety- and depression-like behavior and abnormal mPFC pyramidal neuronal morphology accompanied by alterations in microglial morphology indicative of a heightened state of activation and increased microglial PSD95+ inclusions signifying excessive phagocytosis of the synaptic material in the mPFC. These findings offer novel insights into the neurobehavioral effects due to adolescent HFD consumption and suggest a contributing role in microglial dysfunction and prefrontal neuroplasticity deficits for HFD-associated mood disorders in adolescents.

Discovery of Pyxinol Amide Derivatives Bearing Amino Acid Residues as Nonsubstrate Allosteric Inhibitors of P-Glycoprotein-Mediated Multidrug Resistance.

Nonsubstrate allosteric inhibitors of P-glycoprotein (Pgp), which are considered promising modulators for overcoming multidrug resistance (MDR), are relatively unknown. Herein, we designed and synthesized amino acids bearing amide derivatives of pyxinol, the main ginsenoside metabolite produced by the human liver, and examined their MDR reversal abilities. A potential nonsubstrate inhibitor (7a) was identified to undergo high-affinity binding to the putative allosteric site of Pgp at the nucleotide-binding domains. Subsequent assays confirmed that 7a (25 µM) was able to suppress both basal and verapamil-stimulated Pgp-ATPase activities (inhibition rates of 87 and 60%, respectively) and could not be pumped out by Pgp, indicating that it was a rare nonsubstrate allosteric inhibitor. Moreover, 7a interfered with Pgp-mediated Rhodamine123 efflux while exhibiting high selectivity for Pgp. Notably, 7a also markedly enhanced the therapeutic efficacy of paclitaxel, with a tumor inhibition ratio of 58.1%, when used to treat nude mice bearing KBV xenograft tumors.

Prolonged Early Exposure to a High-Fat Diet Augments the Adverse Effects on Neurobehavior and Hippocampal Neuroplasticity: Involvement of Microglial Insulin Signaling.

High-fat diet (HFD) consumption may contribute to the high prevalence of cognitive-emotional issues in modern society. Mice fed a HFD for a prolonged period develop more severe neurobehavioral disturbances when first exposed to a HFD in the juvenile period than in adulthood, suggesting an initial age-related difference in the detrimental effects of long-term HFD feeding. However, the mechanism underlying this difference remains unclear. Here, male C57BL/6J mice initially aged 4 (IA4W) or 8 (IA8W) weeks were fed a control diet (CD) or HFD for 6 months and then subjected to metabolic, neurobehavioral, and histomorphological examinations. Although the detrimental effects of long-term HFD feeding on metabolism and neurobehavior were observed in mice of both ages, IA4W-HFD mice showed significant cognitive inflexibility accompanied by significantly greater levels of anxiety-like behavior than age-matched controls. Hippocampal neuroplasticity and microglial phenotype were altered by HFD feeding, whereas significant morphological alterations were more frequently observed in IA4W-HFD mice than in IA8W-HFD mice. Additionally, significantly increased hippocampal microglial engulfment of postsynaptic proteins and elevated phospho-insulin-receptor levels were observed in IA4W-HFD, but not in IA8W-HFD, mice. These findings suggest that aberrant microglia-related histomorphological changes in the hippocampus underlie the exacerbated detrimental neurobehavioral effects of prolonged early HFD exposure and indicate that enhanced insulin signaling might drive microglial dysfunction after prolonged early HFD exposure.

Effects of lysate/tissue storage at -80°C on subsequently extracted EVs of epithelial ovarian cancer tissue origins.

Small extracellular vesicles (sEVs) and large extracellular vesicles (lEVs), play vital roles in intercellular communication. We optimized a method that extracts EVs from epithelial ovarian cancer (EOC) tissues for the purpose of investigating whether cryopreservation of EOC tissues affects the phenotypes, contents, and biological functions of extracted EVs. EV morphology, the number and size distribution of EVs, and EV-related markers were analyzed. Storage of lysates at -80°C decreased lEV yield and increased sEV yield, whereas storage of tissues at -80°C increased both sEV and lEV yields; neither changed the morphology or particle mass ratio of EVs. The two cryopreservation groups retained over 90% of proteins and 80% of miRNAs detected in the "fresh" group. EVs extracted following lysate/tissue storage at -80°C could also promote angiogenesis and invasive migration ability in human endothelial cells. Cryopreserved EOC tissue may benefit clinical applications for studies of tissue-derived EVs, especially EV proteins-related ones.

Recognizing schizophrenia using facial expressions based on convolutional neural network.

OBJECTIVE: Facial expressions have been served as clinical symptoms to convey mental conditions in psychiatry. This paper proposes to recognize patients with schizophrenia (SCZ) using their facial images based on deep learning algorithm, and to investigate objective differences in facial expressions between SCZ patients and healthy controls using deep learning algorithm and statistical analyses. METHODS: The study consists of two parts. The first part recruited 106 SCZ patients and 101 healthy controls, and videotaped their facial expressions through a fixed experimental paradigm. The video data were randomly divided into two sets, one for training a convolutional neural network (CNN) with the classification of "healthy control" or "SCZ patient" as output and the other for evaluating the classification result of the trained CNN. In the second part, all facial images of the recruited participants were put into another CNN separately, which was priorly trained with a facial expression database and will output the most likely facial expressions of the recruited participants. Statistical analyses were performed on the obtained facial expressions to find out the objective differences in facial expressions between the two recruited groups. RESULTS: The trained CNN achieved an overall accuracy of 95.18% for classifying "healthy control" or "SCZ patient." Statistical results on the obtained facial expressions demonstrated that the objective differences between the two recruited groups were statistically significant (p < .05). CONCLUSIONS: Facial expressions hold great promise as SCZ clues with the help of deep learning algorithm. The proposed approach would be potentially applied to mobile devices for autorecognizing SCZ in the context of clinical and daily life.

ADE-CycleGAN: A Detail Enhanced Image Dehazing CycleGAN Network.

The preservation of image details in the defogging process is still one key challenge in the field of deep learning. The network uses the generation of confrontation loss and cyclic consistency loss to ensure that the generated defog image is similar to the original image, but it cannot retain the details of the image. To this end, we propose a detail enhanced image CycleGAN to retain the detail information during the process of defogging. Firstly, the algorithm uses the CycleGAN network as the basic framework and combines the U-Net network's idea with this framework to extract visual information features in different spaces of the image in multiple parallel branches, and it introduces Dep residual blocks to learn deeper feature information. Secondly, a multi-head attention mechanism is introduced in the generator to strengthen the expressive ability of features and balance the deviation produced by the same attention mechanism. Finally, experiments are carried out on the public data set D-Hazy. Compared with the CycleGAN network, the network structure of this paper improves the SSIM and PSNR of the image dehazing effect by 12.2% and 8.1% compared with the network and can retain image dehazing details.

Serosurvey for SARS-CoV-2 among blood donors in Wuhan, China from September to December 2019.

The emerging of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused COVID-19 pandemic. The first case of COVID-19 was reported at early December in 2019 in Wuhan City, China. To examine specific antibodies against SARS-CoV-2 in biological samples before December 2019 would give clues when the epidemic of SARS-CoV-2 might start to circulate in populations. We obtained all 88,517 plasmas from 76,844 blood donors in Wuhan between 1 September and 31 December 2019. We first evaluated the pan-immunoglobin (pan-Ig) against SARS-CoV-2 in 43,850 samples from 32,484 blood donors with suitable sample quality and enough volume. Two hundred and sixty-four samples from 213 donors were pan-Ig reactive, then further tested IgG and IgM, and validated by neutralizing antibodies against SARS-CoV-2. Two hundred and thirteen samples (from 175 donors) were only pan-Ig reactive, 8 (from 4 donors) were pan-Ig and IgG reactive, and 43 (from 34 donors) were pan-Ig and IgM reactive. Microneutralization assay showed all negative results. In addition, 213 screened reactive donors were analyzed and did not show obviously temporal or regional tendency, but the distribution of age showed a difference compared with all tested donors. Then we reviewed SARS-CoV-2 antibody results from these donors who donated several times from September 2019 to June 2020, partly tested in a previous published study, no one was found a significant increase in S/CO of antibodies against SARS-CoV-2. Our findings showed no SARS-CoV-2-specific antibodies existing among blood donors in Wuhan, China before 2020, indicating no evidence of transmission of COVID-19 before December 2019 in Wuhan, China.

Design, synthesis, and discovery of Eudistomin Y derivatives as lysosome-targeted antiproliferation agents.

Eudistomin Y is a novel class of ß-carbolines of marine origin with potential antiproliferation activity against MDA-MB-231 cells (triple-negative breast carcinoma). However, the subcellular target or the detailed mechanism against cancer cell proliferation has not yet been identified. In this study, based on its special structure, a novel series of Eudistomin Y fluorescent derivatives were designed and synthesized by enhancing the electron-donor effect of N-9 to endow it with fluorescent properties through N-alkylation. The structure-activity relationships against the proliferation of cancer cells were also analyzed. A quarter of Eudistomin Y derivatives showed much higher potency against cancer cell proliferation than the original Eudistomin Y1. Fluorescent derivative H1k with robust antiproliferative activity could arrest MDA-MB-231 cells in the G2-M phase. The subcellular localization studies of the probes, including H1k, and Eudistomin Y1 were performed in MDA-MB-231 cells, and the co-localization and competitive inhibition assays revealed their lysosome-specific localization. Moreover, H1k could dose-dependently increase the autophagy signal and downregulate the expression of cyclin-dependent kinase (CDK1) and cyclin B1 which principally regulated the G2-M transition. Furthermore, the specific autophagy inhibitor 3-methyladenine significantly inhibited the H1k-triggered antiproliferation of cancer cells and the downregulation of CDK1 and cyclin B1. Overall, the lysosome is identified as the subcellular target of Eudistomin Y for the first time, and derivative H1k showed robust antiproliferative activity against MDA-MB-231 cells by decreasing Cyclin B1-CDK1 complex via a lysosome-dependent pathway.

Effects of Prolonged High-Fat Diet Consumption Starting at Different Ages on Behavioral Parameters and Hippocampal Neuroplasticity in Male Mice.

BACKGROUND: The overconsumption of a high-fat diet (HFD) has been repeatedly blamed as being a possible contributor to the global prevalence of emotional problems in modern society. Our group recently demonstrated the deleterious effect of a chronic HFD throughout adulthood on both emotional behavior and neuroplasticity markers in mice. As a heightened preference for palatable HFDs from the time of the juvenile period (when the brain is particularly vulnerable to environmental insults) is universal among populations around the world, a comparison of the consequences of chronic HFDs starting from juveniles or adults will assist in obtaining better knowledge of the impact that chronic HFDs have on mental health, thus potentially leading to the discovery of more effective strategies for reducing the incidence of psychiatric disorders. METHODS: In the present study, male C57BL/6J mice with an initial age of 4 weeks (IA-4 W) or 8 weeks (IA-8 W) were separately assigned to two subgroups and fed either a control diet (CD, 10 kJ% from fat) or HFD (60 kJ% from fat) for 9 months followed by an analysis focused on metabolic, emotional behavioral, and neuroplastic profiles. RESULTS: The results illustrated that, in addition to abnormal glucolipid metabolism and insulin sensitivity, mice on a chronic HFD exhibited increased levels of anxiety and depression-like behaviors and aberrant hippocampal neuroplasticity. When compared with IA-8 W mice, several changes indicating systemic metabolic disturbance and neurobehavioral disorder after chronic HFD consumption were aggravated in IA-4 W mice, accompanied by exaggerated impairments in hippocampal insulin sensitivity and neurogenesis. CONCLUSIONS: These results not only provide in vivo evidence that the juvenile stage is a critical period of vulnerability to detrimental effects of HFD consumption on metabolic and neuronal function but also suggest dampened hippocampal insulin signaling as a potential link between prolonged HFD consumption and negative neurobehavioral outcomes. Considering the substantial burden posed by psychiatric disorders and the high prevalence of HFD among youth, these observations are meaningful for raising awareness of the harmful effects of excessive dietary fat intake and developing strategy for preventing mental disorders.

[Genetic analysis of a pregnant woman with moderate intellectual disability due to variant of DLG4 gene].

OBJECTIVE: To carry out genetic testing and prenatal diagnosis for a woman featuring moderate intellectual disability (ID). METHODS: The patient had presented at the First Affiliated Hospital of Zhengzhou University on April 28, 2021. With informed consent, peripheral blood and amniotic fluid samples were collected for the extraction of genomic DNA. Pathogenic copy number variations (CNVs) were detected with CNV-seq, and single gene variants were detected by whole exome sequencing (WES) and Sanger sequencing. Candidate variant was verified by Sanger sequencing, and CNV-seq and multiplex ligation-dependent probe amplification (MLPA) were used to detect fetal CNVs. RESULTS: The 23-year-old woman had moderate ID, sideway walking, and unstable holding. Ultrasonography at 18+3 weeks' gestation had revealed no fetal abnormality. No pathogenic CNV was detected in the woman by CNV-Seq, while WES revealed that she has harbored a heterozygous c.1675C>T (p.Arg559*) variant of the DLG4 gene, which was verified by Sanger sequencing. Based on guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be likely pathogenic (PVS1+PM2_supporting). Sanger sequencing has confirmed that the fetus has inherited this variant, and CNV-Seq also revealed that that fetus has harbored a 0.1 Mb heterozygous deletion at Xp21.1, which has encompassed the DMD gene, and the result was verified by MLPA. CONCLUSION: The heterozygous c.1675C>T variant of the DLG4 gene probably underlay the mental retardation in this woman, and her fetus was found to harbor the same variant in addition with deletion of the DMD gene, which may predispose to ID type 62.