Development of Glycan-masked SARS-CoV-2 RBD vaccines against SARS-related coronaviruses.

Emerging and recurrent infectious diseases caused by coronaviruses remain a significant public health concern. Here, we present a targeted approach to elicit antibodies capable of neutralizing SARS-CoV-2 variants and other SARS-related coronaviruses. By introducing amino acid mutations at mutation-prone sites, we engineered glycosylation modifications to the Receptor Binding Domain (RBD) of SARS-CoV-2, thereby exposing more conserved, yet less accessible epitopes. We developed both messenger RNA (mRNA) and recombination subunit vaccines using these engineered-RBDs (M1, M2) and the wild-type RBD as immunogens. The engineered-RBD vaccines elicited robust neutralizing responses against various SARS-CoV-2 variants as well as SARS-CoV and WIV1-CoV, and conferred protection in mice challenged with the XBB.1.16 strain. Furthermore, We highlighted that glycan masking is a decisive factor in antibody binding changes and RBD-conserved antibody response. Additionally, the glycan-engineered RBD mRNA vaccines stimulated stronger cell-mediated immune responses. Our glycan modification strategy significantly enhances broad-spectrum neutralizing efficacy and cellular immunity, providing valuable insights for the development of vaccines against a wide range of SARS-related coronaviruses.

A 3D hierarchical TiO2/CaIn2S4/C3N4arrays photoanode with dual-heterojunction for enhanced photoelectrochemical performance.

A novel 3D hierarchical TiO2/CaIn2S4/C3N4arrays with dual heterojunctions photoanode is constructed by stepwise deposition of CaIn2S4nanosheets and ultrathin C3N4onto the well-aligned TiO2nanorods arrays. Integrating the merit of the superior ability of CaIn2S4and C3N4to harvest visible light, dual type-Ⅱ heterojunction band structure and one-dimensional ordered nanostructures, the TiO2/CaIn2S4/C3N4photoanode exhibits simultaneous significant improvements in visible-light harvesting, charge separation and electron transfer capability. At 1.23 V (versus reversible hydrogen electrode) under AM 1.5 G irradiation, the TiO2/CaIn2S475/C3N4photoanode exhibits a photocurrent density of 4.5 mA cm-2, which is 5.2 and 51.1-fold higher than that of TiO2/CaIn2S475 and pristine TiO2photoanode, respectively. Moreover, the applied bias photo-to-current efficiency (ABPE) of the TiO2/CaIn2S475/C3N4photoanode reaches 3.5% at 0.36 V (versus reversible hydrogen electrode). These results are helpful for fabricating more efficient heterostructure photoelectrodes.

Ultrafast MUTC photodiodes over 200†GHz with high saturation power.

Novel back-illuminated modified uni-traveling-carrier photodiodes (MUTC-PDs) with wide bandwidth and high saturation power are demonstrated. The effect of cliff layer doping on the electric field distribution is investigated to achieve fast carrier transport. MUTC-PDs with miniaturized device diameter and low contact resistance are fabricated to improve the RC-limited bandwidth. Meanwhile, inductive peaking is implemented to further extend the bandwidth. PDs with 3-µm and 3.6-µm-diameter exhibit a ultrawide bandwidth of 230 GHz and 200 GHz, together with -4.94 dBm and -2.14 dBm saturation power at 220 GHz and 200 GHz, respectively.

Accurate Prediction of Soil Heavy Metal Pollution Using an Improved Machine Learning Method: A Case Study in the Pearl River Delta, China.

In traditional soil heavy metal (HM) pollution assessment, spatial interpolation analysis is often carried out on the limited sampling points in the study area to get the overall status of heavy metal pollution. Unfortunately, in many machine learning spatial information enhancement algorithms, the additional spatial information introduced fails to reflect the hierarchical heterogeneity of the study area. Therefore, we designed hierarchical regionalization labels based on three interpolation techniques (inverse distance weight, ordinary kriging, and trend surface interpolation) as new spatial covariates for a machine learning (ML) model. It was demonstrated that regional spatial information improved the prediction performance of the model (R2 > 0.7). On the basis of the prediction results, the status of HM pollution in the Pearl River Delta (PRD) region was evaluated: cadmium (Cd) and copper (Cu) were the most serious pollutants in the PRD (the point overstandard rates are 18.77% and 12.95%, respectively). The analysis of index importance and bivariate local indicators of spatial association (LISA) shows that the key factors affecting the spatial distribution of heavy metals are geographical and climatic conditions [namely, altitude, humidity index, and normalized vegetation difference index (NDVI)] and some industrial activities (such as metal processing, printing and dyeing, and electronics industry). This study develops a novel approach to improve existing spatial interpolation techniques, which will enable more precise and scientific soil environmental management.

Digital mapping of soil organic carbon density in China using an ensemble model.

The soil organic carbon stock (SOCS) is considered as one of the largest carbon reservoirs in terrestrial ecosystems, and small changes in soil can cause significant changes in atmospheric CO2 concentration. Understanding organic carbon accumulation in soils is crucial if China is to meet its dual carbon target. In this study, the soil organic carbon density (SOCD) in China was digitally mapped using an ensemble machine learning (ML) model. First, based on SOCD data obtained at depths of 0-20 cm from 4356 sampling points (15 environmental covariates), we compared the performance of four ML models, namely random forest (RF), extreme gradient boosting (XGBoost), support vector machine (SVM), and artificial neural network (ANN) models, in terms of coefficient of determination (R2), mean absolute error (MAE), and root mean square error (RMSE) values. Then, we ensembled four models using Voting Regressor and the principle of stacking. The results showed that ensemble model (EM) accuracy was high (RMSE = 1.29, R2 = 0.85, MAE = 0.81), so that it could be a good choice for future research. Finally, the EM was used to predict the spatial distribution of SOCD in China, which ranged from 0.63 to 13.79 kg C/m2 (average = 4.09 (±1.90) kg C/m2). The SOC storage amount in surface soil (0-20 cm) was 39.40 Pg C. This study developed a novel, ensemble ML model for SOC prediction, and improved our understanding of the spatial distribution of SOC in China.

Screening of Genes Co-Associated with Sudden Infant Death Syndrome and Infectious Sudden Death in Infancy and Bioinformatics Analysis of Their Regulatory Networks.

OBJECTIVES: The common differentially expressed mRNAs in brain, heart and liver tissues of deceased sudden infant death syndrome (SIDS) and infectious sudden death in infancy (ISDI) confirmed by autopsy was screened by bioinformatics to explore the common molecular markers and pathogenesis of SIDS and ISDI. METHODS: The datasets of GSE70422 and GSE136992 were downloaded, the limma of R software was used to screen differentially expressed mRNA in different tissue samples of SIDS and ISDI decedents for overlapping analysis. The clusterProfiler of R software was used to conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The protein-protein interaction (PPI) network was constructed by STRING database, while the hub gene was screened by cytoHubba plug-in. RESULTS: Compared with the control group, there were 19 significant differentially expressed genes in the tissue samples of SIDS and ISDI decedents, among which 16 in the heart tissue and 3 in the liver tissue, and the astrotactin 1 (ASTN1) gene expression difference in the heart tissue was most significant. The PPI network identified Ras homolog family member A (RHOA), integrin subunit alpha 1 (ITGA1), and H2B clustered histone 5 (H2BC5) were hub genes. The analysis of GO and KEGG showed that differentially expressed genes were enriched in the molecular pathways of actin cytoskeleton regulation, focal adhesion and response to mycophenolic acid. CONCLUSIONS: ASTN1, RHOA and ITGA1 may participate in the development of SIDS and ISDI. The enrichment of differentially expressed genes in immune and inflammatory pathways suggests a common molecular regulatory mechanism between SIDS and ISDI. These findings are expected to provide new biomarkers for molecular anatomy and forensic identification of SIDS and ISDI.

Eugenol alleviated nonalcoholic fatty liver disease in rat via a gut-brain-liver axis involving glucagon-like Peptide-1.

Eugenol, an active ingredient of many medicinal aromatic plants, has been proved to have the hypolipidemic effect, but its potential mechanism of action is still unknown. This study aimed to investigate whether eugenol regulates liver lipid accumulation in high-fat diet (HFD) induced nonalcoholic fatty liver disease (NAFLD) rats via the gut-brain-liver axis involving glucagon-like peptide-1 (GLP-1). Hepatic vagotomy was performed in NAFLD rats to determine the role of eugenol in regulating hepatic lipid accumulation via vagus nerve. The results showed that after eight weeks of eugenol administration in NAFLD rats, serum total cholesterol (TC), triglyceride (TG) and hepatic TG decreased. However, eugenol showed no significant effect on the increased food intakes and weight gain caused by the HFD. Eugenol promoted the secretion of GLP-1 into the blood, increased GLP-1 receptor (GLP-1R) expression in the duodenum, liver, arcuate nucleus (ARC) and paraventricular nucleus (PVN), increased c-fos expression in the nucleus tractus solitarii (NTS), and promoted ZO-1 and occludin expression in duodenum. Furthermore, steatosis and lipid accumulation were significantly alleviated. Hepatic vagotomy partially attenuated the improvement of eugenol in hepatic lipid accumulation in NAFLD rats. In conclusion, eugenol regulates hepatic lipid metabolism via a gut-brain-liver axis involving in GLP-1, providing a new strategy for the treatment of NAFLD.

Insulin-like signaling promotes limb regeneration in the Chinese mitten crab (Eriocheir sinensis).

In the pond culture of Chinese mitten crabs, limb autotomy seriously affects the feeding efficiency, immunity and survival. Therefore, it is crucial to understand the mechanism of limb regeneration of mitten crabs, so that culture strategies could be developed to reduce the limb impairment rate. The insulin-like signaling (ILS) pathway is evolutionarily conserved, and plays key roles in the growth and immunity of various species. In this study, a full-length cDNA of insulin-like receptor (EsInR) was identified from Eriocheir sinensis, and its mRNA expression patterns during limb regeneration was evaluated. The cDNA of EsInR includes a 4326 bp ORF encoding a protein of 1441 amino acids, with conserved α-and ß-subunits. The EsInR and genes related to ILS were found to be upregulated during limb regeneration, which indicated that ILS plays a key role in limb regeneration of E. sinensis. Our experiment revealed that inhibition of ILS through injection of the InR inhibitor GSK1838705A at the blastema formation stage significantly reduced the limb regeneration rate compared to control group. In addition, injection of GSK1838705A also reduced the size of newly formed limbs after the molting cycle. Furthermore, we found that genes related to myogenesis were downregulated following injection of InR inhibitor both before and after molting. The results also indicated that cyclins and CDK1 were downregulated, while CKIs were upregulated following treatment with the InR inhibitor. These results suggest that ILS regulates limb regeneration in E. sinensis by promoting muscle growth and regeneration in response to autotomy stress. Thus, we identified a conserved insulin-like receptor in E. sinensis, and provide new evidence for the involvement of ILS in the regulation of limb autotomy and regeneration in crustaceans.

Characters and environmental driving factors of bacterial community in soil of Beijing urban parks.

In an era of unprecedented human influence, different human activities have different degrees of impact on specific bacteria, resulting in the regional biological homogenization of soil bacteria. However, the contribution of the impact that a large number of anthropogenic activities on bacteria remains unknown. Here, by high-throughput amplicon sequencing, we characterized the composition, diversity and influencing factors of soil microbes in Beijing urban parks at geographic space and park management aspect. It is the first time to quantify and compare the importance of the impact of up to 15 human activities on soil bacterial communities. The results show that the dominant bacterial phyla in Beijing urban parks were Actinobacteria, Proteobacteria, Acidobacteria and Chloroflexi. The environmental management of different park types, as well as the land use history and development conditions of different regions, had significant differences in soil bacterial community structure. Soil bacteria in urban parks were disturbed by direct human interference far more than natural causes. The most important factors were related to the number of tourists and residents, industrial production and land use patterns. These factors may also be related to the abundance of unknown bacteria in urban parks. This also directly shows that human activities have a non-negligible impact on soil bacteria. The ways in which different human activities brought by global urbanization and their impacting mechanisms are used should be the starting point of future research.

Human health risk-based soil environmental criteria (SEC) for park soil in Beijing, China.

Urban parks are important places that allow urban residents to experience nature but are also associated with the risk of exposure to contaminated soil. Therefore, it is necessary to establish appropriate soil environment criteria (SEC) to manage park soil quality. Studies on the demographic characteristics and behavioral patterns of urban park visitors are helpful for the selection of sensitive receptors and the determination of parameters in the establishment of SEC. This study explored the park visitors' demographic characteristics and behavioral patterns, and applied the results to derive SEC. Eighty-six parks in Beijing were selected, and mobile phone data were obtained to analysis the demographic characteristics and residence time of the visitors. Kruskal-Wallis test, kernel density estimation and random forest model were used for data analysis. The CLEA model was used to derive SEC. The results showed that the demographic characteristics and behavioral patterns of visitors in different types of parks were quite different. Parks were mostly used by males and visitors aged 31-45. Most visitors stayed in the park for 1-2 h, and the distance from a given visitor's home to the park was the most important factor affecting stay time. Then, several parameters such as the parameters related to the receptors and occupation period were optimized, and the SEC of sensitive parks and non-sensitive parks were derived. Exposure frequency may be the main reason for the difference of SEC between the two types of parks. The SECs of sensitive parks were higher than the soil screening values (SSVs) for class 1 land in GB36600-2018, indicating that the current SSVs for some parks may be too conservative. This study provides a reference for the formulation and revision of soil environmental standards for park land, and suggests strengthening research on human behavioral patterns.

Dynamic Variation of Amino Acid Contents and Identification of Sterols in Xinyang Mao Jian Green Tea.

As important biomolecules in Camellia sinensis L., amino acids (AAs) are considered to contribute to the overall green tea sensory quality and undergo dynamic changes during growth. However, limited by analytical capacity, detailed AAs composition in different growth stages remains unclear. To address this question, we analyzed the dynamic changes of 23 AAs during leaf growth in Xinyang Mao Jian (XYMJ) green tea. Using amino acid analyzer, we demonstrated that most AAs are abundant on Pure Brightness Day and Grain Rain Day. After Grain Rain, 23 AAs decreased significantly. Further analysis shows that theanine has a high level on the day before Spring Equinox and Grain Rain, accounting for 44-61% of the total free AAs content in tea leaves. Glu, Pro, and Asp are the second most abundant AAs. Additionally, spinasterol and 22,23-dihydrospinasterol are first purified and identified in ethanol extract of XYMJ by silica gel column chromatography method. This study reveals the relationship between plucking days and the dynamic changes of AAs during the growth stage and proves the rationality of the traditional plucking days of XYMJ green tea.

Development, Characterization, and Investigation of In Vivo Targeted Delivery Efficacy of Luteolin-Loaded, Eudragit S100-Coated mPEG-PLGA Nanoparticles.

Luteolin (Lu) is a kind of flavonoid that has been proved to treat non-alcoholic fatty liver disease by alleviating intestinal microbiota disorder. In this study, luteolin was coated with methoxy poly(ethylene glycol)-poly(dl-lactide-co-glycolic acid) (mPEG-PLGA) using an emulsion solvent evaporation method, and the optimum preparation process was determined by a single-factor experiment combined with response surface methodology (RSM). Methacrylic acid-methyl methacrylate (1:2) copolymer (Eudragit S100) was then used to coat the surface of Lu/mPEG-PLGA nanoparticles. The physical parameters of Eudragit S100-coated Lu/mPEG-PLGA nanoparticles (Lu-NPs), such as appearance, particle size, potential, particle size distribution and drug release, and stability in vitro, were evaluated. In addition, its cytotoxicity in vitro, pharmacokinetics, tissue distribution, and toxicity in vivo were also studied. The results showed that the prepared Lu-NPs had uniform particle size distribution, high encapsulation efficiency, and good stability. Normal colonic epithelial cells showed good tolerance to Lu-NPs. After oral administration, the blood concentration of luteolin peaked at 8 h, and the main tissue distribution was within the colon, confirming its colon-targeted profile. Safety assessments also indicated that no significant changes were observed in main organs after administration of Lu-NPs. The use of Eudragit S100-coated Lu/mPEG-PLGA nanoparticles is a new strategy for colon-targeted delivery of luteolin that encourages luteolin to fulfill its role in the colon.

Forecast daily tourist volumes during the epidemic period using COVID-19 data, search engine data and weather data.

The COVID-19 epidemic has brought a devastating blow to the tourism industry. Affected by the epidemic situation, the change of tourism volume of scenic spots is very unstable. Therefore, forecasting tourist volume in the context of COVID-19 epidemic is a new and challenging problem. In response, a novel multivariate time series forecasting framework based on variational mode decomposition (VMD) and gated recurrent unit network (GRU), i.e., VMD-GRU, is proposed to forecast daily tourist volumes during the epidemic. It takes the lead in using COVID-19 data, search traffic data and weather data. Through sufficient experiments and comparisons, the superiority of the approach is illustrated, and the predictive power of the above three types of data, especially the COVID-19 data, is revealed. Accurate forecast results from the method can help relevant government officials and tourism practitioners to better adjust tourism resources, cooperate with anti-epidemic work and reduce operational risks.

Semi-Supervised Cross-Subject Emotion Recognition Based on Stacked Denoising Autoencoder Architecture Using a Fusion of Multi-Modal Physiological Signals.

In recent decades, emotion recognition has received considerable attention. As more enthusiasm has shifted to the physiological pattern, a wide range of elaborate physiological emotion data features come up and are combined with various classifying models to detect one's emotional states. To circumvent the labor of artificially designing features, we propose to acquire affective and robust representations automatically through the Stacked Denoising Autoencoder (SDA) architecture with unsupervised pre-training, followed by supervised fine-tuning. In this paper, we compare the performances of different features and models through three binary classification tasks based on the Valence-Arousal-Dominance (VAD) affection model. Decision fusion and feature fusion of electroencephalogram (EEG) and peripheral signals are performed on hand-engineered features; data-level fusion is performed on deep-learning methods. It turns out that the fusion data perform better than the two modalities. To take advantage of deep-learning algorithms, we augment the original data and feed it directly into our training model. We use two deep architectures and another generative stacked semi-supervised architecture as references for comparison to test the method's practical effects. The results reveal that our scheme slightly outperforms the other three deep feature extractors and surpasses the state-of-the-art of hand-engineered features.

Transcriptomic Analysis Reveals an Altered Hcy Metabolism in the Stria Vascularis of the Pendred Syndrome Mouse Model.

Purpose: Slc26a4-/- mice exhibit severer defects in the development of the cochlea and develop deafness, while the underlying mechanisms responsible for these effects remain unclear. Our study was to investigate the potential mechanism linking SLC26A4 deficiency to hearing loss. Materials and Methods: RNA sequencing was applied to analyze the differential gene expression of the stria vascularis (SV) from wildtype and Slc26a4-/- mice. GO and KEGG pathway analysis were performed. Quantitative RT-PCR was applied to validate the expression of candidate genes affected by Slc26a4. ELISA and immunofluorescence technique were used to detect the homocysteine (Hcy) level in serum, brain, and SV, respectively. Results: 183 upregulated genes and 63 downregulated genes were identified in the SV associated with Slc26a4 depletion. Transcriptomic profiling revealed that Slc26a4 deficiency significantly affected the expression of genes associated with cell adhesion, transmembrane transport, and the biogenesis of multicellular organisms. The SV from Slc26a4-/- mice exhibited a higher expression of Bhmt mRNAs, as well as altered homocysteine (Hcy) metabolism. Conclusions: The altered expression of Bhmt results in a dramatic change in multiple biochemical reactions and a disruption of nutrient homeostasis in the endolymph which may contribute to hearing loss of Slc26a4 knockout mouse.

Early enteral feeding after intestinal anastomosis in children: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Delayed enteral feeding (DEF) contributes to postoperative complications among children undergoing intestinal surgery. Various recent studies indicate the benefits of early enteral nutrition after intestinal surgery in adults. This systematic review and meta-analysis evaluates whether early enteral feeding (EEF) is beneficial in children who underwent intestinal anastomosis. METHODS: MEDLINE, PubMed, the Cochrane Library, and Web of Science databases were searched for RCTs that addressed the effect of EEF in children (younger than 18 years old) undergoing intestinal anastomosis. EEF was defined as starting enteral feeding before the 3rd postoperative day. Studies were selected based on predetermined inclusion and exclusion criteria. A meta-analysis was performed using RevMan 5.3 to estimate odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: Four RCT studies met the inclusion criteria, comprising 97 cases with EEF and 89 cases with DEF. Enteral feeding started significantly earlier in the EEF group compared to the DEF group (MD = - 2.80; 95% CI - 3.11 to - 2.49; p < 0.00001). Postoperative anastomotic leak rate was unchanged between EEF and DEF groups (OR = 0.86; 95% CI 0.17-4.46; p = 0.86). The EEF group had a shorter length of hospital stay (MD = - 3.38; 95% CI - 4.29 to - 2.48; p < 0.00001), earlier time to bowel movement return (MD = - 0.57; 95% CI - 0.79 to - 0.35; p < 0.00001), lower incidence of surgical infection (OR = 0.27; 95% CI 0.08-0.90; p = 0.03), and faster tolerance of full enteral feeding (MD = - 2.00; 95% CI - 3.01 to - 2.79; p < 0.00001). Incidence of fever (OR = 0.37; 95% CI 0.10-1.31; p = 0.12), emesis, and abdominal distention (OR = 0.63; 95% CI 0.13-3.16; p = 0.58) were not different between the two groups. CONCLUSIONS: Early enteral feeding after intestinal anastomosis in children does not increase the risk of postoperative anastomotic leak, fever, emesis, and abdominal distention. However, early enteral feeding is beneficial as it promotes the return of bowel function, reduces the length of hospital stay and the incidence of surgical infection in comparison to delayed enteral feeding.

A full-length transcriptome and gene expression analysis reveal genes and molecular elements expressed during seed development in Gnetum luofuense.

BACKGROUND: Gnetum is an economically important tropical and subtropical gymnosperm genus with various dietary, industrial and medicinal uses. Many carbohydrates, proteins and fibers accumulate during the ripening of Gnetum seeds. However, the molecular mechanisms related to this process remain unknown. RESULTS: We therefore assembled a full-length transcriptome from immature and mature G. luofuense seeds using PacBio sequencing reads. We identified a total of 5726 novel genes, 9061 alternative splicing events, 3551 lncRNAs, 2160 transcription factors, and we found that 8512 genes possessed at least one poly(A) site. In addition, gene expression comparisons of six transcriptomes generated by Illumina sequencing showed that 14,323 genes were differentially expressed from an immature stage to a mature stage with 7891 genes upregulated and 6432 genes downregulated. The expression of 14 differentially expressed transcription factors from the MADS-box, Aux/IAA and bHLH families was validated by qRT-PCR, suggesting that they may have important roles in seed ripening of G. luofuense. CONCLUSIONS: These findings provide a valuable molecular resource for understanding seed development of gymnosperms.

Nicotinamide phosphoribosyltransferase secreted from microglia via exosome during ischemic injury.

Nicotinamide phosphoribosyltransferase (NAMPT) is the key enzyme of the salvage pathway of nicotinamide adenine dinucleotide synthesis. NAMPT can also be secreted and functions as a cytokine. We have previously shown that in the brain, NAMPT expression and secretion can be induced in microglia upon neuroinflammation and injury. Yet the mechanism for NAMPT secretion remains unclear. Here we show that NAMPT can be actively secreted from microglia upon the treatment of ischemia-like injury - oxygen-glucose deprivation and recovery (OGD/R). We confirmed that classical ER-Golgi pathway is not involved in NAMPT secretion. NAMPT secretion was further enhanced by ATP, and the secretion was mediated by P2X7 receptor and by intracellular Ca2+ . Importantly, we found that phospholipase D inhibitor, n-butanol, phospholipase D siRNA, and wortmannin significantly decreased OGD/R-induced and ATP-enhanced release of NAMPT in microglia. After excluding the mechanisms of involving secretory autophagy, endosomes, and secretory lysosome, we have concluded that microglial NAMPT is secreted mainly via exosome. Immune-electron microscopy identifies NAMPT in extracellular vesicles with the size and morphology characteristic of exosome. With the vesicles harvested by ultra-centrifugation, exosomal NAMPT is further confirmed by Western blotting analysis. Intriguingly, the amount of NAMPT relative to exosomal protein markers remains unchanged upon the treatment of OGD/R, suggesting a constant load of exosomal NAMPT in microglia. Taken together, we have identified NAMPT is actively secreted via exosome from microglia during neuroinflammation of ischemic injury.

Reduced expression of synapsin II in a chronic phencyclidine preclinical rat model of schizophrenia.

Schizophrenia is a mental disorder characterized by positive symptoms, negative symptoms, and cognitive dysfunction. Phencyclidine (PCP)-a N-methyl-D-aspartate (NMDA) receptor antagonist-induces symptoms indistinguishable from those of schizophrenia. A reduction of the phosphoprotein synapsin II has also been implicated in schizophrenia and has a well-known role in the maintenance of the presynaptic reserve pool and vesicle mobilization. This study assessed the behavioral and biochemical outcomes of chronic NMDA receptor antagonism in rodents and its implications for the pathophysiology of schizophrenia. Sprague Dawley rats received saline or chronic PCP (5 mg/kg/day) for 14 days via surgically implanted Alzet® osmotic mini-pumps. Following the treatment period, rats were tested with a series of behavioral paradigms, including locomotor activity, social interaction, and sensorimotor gating. Following behavioral assessment, the medial prefrontal cortex (mPFC) of all rats was isolated for synapsin II protein analysis. Chronic PCP treatment yielded a hyper-locomotive state (p = 0.0256), reduced social interaction (p = 0.0005), and reduced pre-pulse inhibition (p < 0.0001) in comparison to saline-treated controls. Synapsin IIa (p < 0.0001) and IIb (p < 0.0071) levels in the mPFC of chronically treated PCP rats were reduced in comparison to the saline group. Study results confirm that rats subject to chronic PCP treatment display behavioral phenotypes similar to established preclinical animal models of schizophrenia. Reduction of synapsin II expression in this context implicates the role of this protein in the pathophysiology of schizophrenia and sheds light on the longer-term consequences of NMDA receptor antagonism facilitated by chronic PCP treatment.

Single-Molecule Long-Read Sequencing Reveals the Diversity of Full-Length Transcripts in Leaves of Gnetum (Gnetales).

The limitations of RNA sequencing make it difficult to accurately predict alternative splicing (AS) and alternative polyadenylation (APA) events and long non-coding RNAs (lncRNAs), all of which reveal transcriptomic diversity and the complexity of gene regulation. Gnetum, a genus with ambiguous phylogenetic placement in seed plants, has a distinct stomatal structure and photosynthetic characteristics. In this study, a full-length transcriptome of Gnetum luofuense leaves at different developmental stages was sequenced with the latest PacBio Sequel platform. After correction by short reads generated by Illumina RNA-Seq, 80,496 full-length transcripts were obtained, of which 5269 reads were identified as isoforms of novel genes. Additionally, 1660 lncRNAs and 12,998 AS events were detected. In total, 5647 genes in the G. luofuense leaves had APA featured by at least one poly(A) site. Moreover, 67 and 30 genes from the bHLH gene family, which play an important role in stomatal development and photosynthesis, were identified from the G. luofuense genome and leaf transcripts, respectively. This leaf transcriptome supplements the reference genome of G. luofuense, and the AS events and lncRNAs detected provide valuable resources for future studies of investigating low photosynthetic capacity of Gnetum.