Psychosocial and psychological interventions for schizophrenia relapse prevention: A bibliometric analysis.

Various psychosocial and psychological interventions have been developed to reduce schizophrenia relapse prevention. A better understanding of these active interventions is important for clinical practice and for meaningful allocation of resources. However, no bibliometric analysis of this area has been conducted. Studies were retrieved from the Web of Science Core Collection database. The publication outputs and cooperation of institutions were visualized with Origin 2021. Global cooperation was visualized using ArcGIS Pro3.0. VOSviewer was used to generate visualizations of network of authors and keywords. The number of annual publications generally showed a fluctuating upward trend over the past 20 years. Germany published the most relevant articles (361, 26.76%). The Technical University of Munich was the most productive institution (70, 9.86%). Leucht Stefan published the most articles (46, 6.48%) and had the highest number of citations (4,375 citations). Schizophrenia Research published the most studies (39, 5.49%). Keywords were roughly classified into three clusters: cognitive behavioral therapy (CBT), family interventions and family psychoeducation and other factors related to interventions. The findings provided the current status of research on psychosocial and psychological interventions for schizophrenia relapse prevention from a bibliometric perspective. Recent research has mainly focused on CBT, family interventions and family psychoeducation.

A Multifunctional CaII-EuIII Heterometallic Organic Framework with Sensing and Selective Adsorption in Water.

With increasing global industrialization, it is urgent and challenging to develop multifunctional species for detection and adsorption in the environment. For this purpose, a novel anionic heterometallic organic framework, [(CH3)2NH2][CaEu(CAM)2(H2O)2]·4H2O·4DMF (CaEuCAM), is hydrothermally synthesized based on chelidamic acid (H3CAM). Single crystal analysis shows that CaEuCAM features two different oxygen-rich channels along the c-axis in which one CAM3- bridges two sextuple-coordinated Ca2+ and two octuple-coordinated Eu3+ with a µ4-η1: η1: η1: η1: η1: η1 new chelating and bridging mode. The characteristic bright red emission and superior hydrostability of CaEuCAM under harsh acidic and basic conditions benefit it by acting as a highly sensitive sensor for Fe3+ and 3-nitrophenol (3-NP) with extremely low LODs through remarkable quenching. The combination of experiments and theoretical calculations for sensing mechanisms shows that the competitive absorption and interaction are responsible for Fe3+-induced selective emission quenching, while that for 3-NP is the result of the synergism of host-guest chemistry and the inner filter effect. Meanwhile, the assimilation of negative charge plus channels renders CaEuCAM a highly selective adsorbent for methylene blue (MB) due to a synergy of electrostatic affinity, ion-dipole interaction, and size matching. Of note is the reusability of CaEuCAM toward Fe3+/3-NP sensing and MB adsorption besides its fast response. These findings could be very useful in guiding the development of multifunctional Ln-MOFs for sensing and adsorption applications in water media.

PagPXYs improve drought tolerance by regulating reactive oxygen species homeostasis in the cambium of Populus alba × P. glandulosa.

PXY (Phloem intercalated with xylem) is a receptor kinase required for directional cell division during the development of plant vascular tissue. Drought stress usually affects plant stem cell division and differentiation thereby limiting plant growth. However, the role of PXY in cambial activities of woody plants under drought stress is unclear. In this study, we analyzed the biological functions of two PXY genes (PagPXYa and PagPXYb) in poplar growth and development and in response to drought stress in a hybrid poplar (Populus alba × P. glandulosa, '84K'). Expression analysis indicated that PagPXYs, similar to their orthologs PtrPXYs in Populus trichocarpa, are mainly expressed in the stem vascular system, and related to drought. Interestingly, overexpression of PagPXYa and PagPXYb in poplar did not have a significant impact on the growth status of transgenic plants under normal condition. However, when treated with 8 % PEG6000 or 100 mM H2O2, PagPXYa and PagPXYb overexpressing lines consistently exhibited more cambium cell layers, fewer xylem cell layers, and enhanced drought tolerance compared to the non-transgenic control '84K'. In addition, PagPXYs can alleviate the damage caused by H2O2 to the cambium under drought stress, thereby maintaining the cambial division activity of poplar under drought stress, indicating that PagPXYs play an important role in plant resistance to drought stress. This study provides a new insight for further research on the balance of growth and drought tolerance in forest trees.

PdRabG3f interfered with gibberellin-mediated internode elongation and xylem developing in poplar.

As a member of the small GTPases family, Rab GTPases play a key role in specifying transport pathways in the intracellular membrane trafficking system and are involved in plant growth and development. By quantitative trait locus (QTL) mapping, PdRabG3f was identified as a candidate gene associated with shoot height in a hybrid offspring of Populus deltoides 'Danhong' × Populus simonii 'Tongliao1'. PdRabG3f localized to the nucleus, endoplasmic reticulum and tonoplast and was primarily expressed in the xylem and cambium. Overexpression of PdRabG3f in Populus alba × Populus glandulosa (84 K poplar) had inhibitory effects on vertical and radical growth. In the transgenic lines, there were evident changes in the levels of 15 gibberellin (GA) derivatives, and the application of exogenous GA3 partially restored the phenotypes mediated by GAs deficiency. The interaction between PdRabG3f and RIC4, which was the GA-responsive factor, provided additional explanation for PdRabG3f's inhibitory effect on poplar growth. RNA-seq analysis revealed differentially expressed genes (DEGs) associated with cell wall, xylem, and gibberellin response. PdRabG3f interfering endogenous GAs levels in poplar might involve the participation of MYBs and ultimately affected internode elongation and xylem development. This study provides a potential mechanism for gibberellin-mediated regulation of plant growth through Rab GTPases.

Growth-regulating factor 15-mediated vascular cambium differentiation positively regulates wood formation in hybrid poplar (Populus alba × P. glandulosa).

Introduction: Hybrid poplars are industrial trees in China. An understanding of the molecular mechanism underlying wood formation in hybrid poplars is necessary for molecular breeding. Although the division and differentiation of vascular cambial cells is important for secondary growth and wood formation, the regulation of this process is largely unclear. Methods: In this study, mPagGRF15 OE and PagGRF15-SRDX transgenic poplars were generated to investigate the function of PagGRF15. RNA-seq and qRT-PCR were conducted to analyze genome-wide gene expression, while ChIP‒seq and ChIP-PCR were used to identified the downstream genes regulated by PagGRF15. Results and discussion: We report that PagGRF15 from hybrid poplar (Populus alba × P. glandulosa), a growth-regulating factor, plays a critical role in the regulation of vascular cambium activity. PagGRF15 was expressed predominantly in the cambial zone of vascular tissue. Overexpression of mPagGRF15 (the mutated version of GRF15 in the miR396 target sequence) in Populus led to decreased plant height and internode number. Further stem cross sections showed that the mPagGRF15 OE plants exhibited significant changes in vascular pattern with an increase in xylem and a reduction in phloem. In addition, cambium cell files were decreased in the mPagGRF15 OE plants. However, dominant suppression of the downstream genes of PagGRF15 using PagGRF15-SRDX showed an opposite phenotype. Based on the RNA-seq and ChIP-seq results, combining qRT-PCR and ChIP-PCR analysis, candidate genes, such as WOX4b, PXY and GID1.3, were obtained and found to be mainly involved in cambial activity and xylem differentiation. Accordingly, we speculated that PagGRF15 functions as a positive regulator mediating xylem differentiation by repressing the expression of the WOX4a and PXY genes to set the pace of cambial activity. In contrast, PagGRF15 mediated the GA signaling pathway by upregulating GID1.3 expression to stimulate xylem differentiation. This study provides valuable information for further studies on vascular cambium differentiation mechanisms and genetic improvement of the specific gravity of wood in hybrid poplars.

Identifying frequency-dependent imaging genetic associations via hypergraph-structured multi-task sparse canonical correlation analysis.

Identifying complex associations between genetic variations and imaging phenotypes is a challenging task in the research of brain imaging genetics. The previous study has proved that neuronal oscillations within distinct frequency bands are derived from frequency-dependent genetic modulation. Thus it is meaningful to explore frequency-dependent imaging genetic associations, which may give important insights into the pathogenesis of brain disorders. In this work, the hypergraph-structured multi-task sparse canonical correlation analysis (HS-MTSCCA) was developed to explore the associations between multi-frequency imaging phenotypes and single-nucleotide polymorphisms (SNPs). Specifically, we first created a hypergraph for the imaging phenotypes of each frequency and the SNPs, respectively. Then, a new hypergraph-structured constraint was proposed to learn high-order relationships among features in each hypergraph, which can introduce biologically meaningful information into the model. The frequency-shared and frequency-specific imaging phenotypes and SNPs could be identified using the multi-task learning framework. We also proposed a useful strategy to tackle this algorithm and then demonstrated its convergence. The proposed method was evaluated on four simulation datasets and a real schizophrenia dataset. The experimental results on synthetic data showed that HS-MTSCCA outperforms the other competing methods according to canonical correlation coefficients, canonical weights, and cosine similarity. And the results on real data showed that HS-MTSCCA could obtain superior canonical coefficients and canonical weights. Furthermore, the identified frequency-shared and frequency-specific biomarkers could provide more interesting and meaningful information, demonstrating that HS-MTSCCA is a powerful method for brain imaging genetics.

Gut microbial diversity moderates polygenic risk of schizophrenia.

Background: Schizophrenia (SCZ) is a heritable disorder with a polygenic architecture, and the gut microbiota seems to be involved in its development and outcome. In this study, we investigate the interplay between genetic risk and gut microbial markers. Methods: We included 159 first-episode, drug-naïve SCZ patients and 86 healthy controls. The microbial composition of feces was characterized using the 16S rRNA sequencing platform, and five microbial α-diversity indices were estimated [Shannon, Simpson, Chao1, the Abundance-based Eoverage Estimator (ACE), and a phylogenetic diversity-based estimate (PD)]. Polygenic risk scores (PRS) for SCZ were constructed using data from large-scale genome-wide association studies. Effects of microbial α-diversity, microbial abundance, and PRS on SCZ were evaluated via generalized linear models. Results: We confirmed that PRS was associated with SCZ (OR = 2.08, p = 1.22×10-5) and that scores on the Shannon (OR = 0.29, p = 1.15×10-8) and Simpson (OR = 0.29, p = 1.25×10-8) indices were inversely associated with SCZ risk. We found significant interactions (p < 0.05) between PRS and α-diversity indices (Shannon, Simpson, and PD), with the effects of PRS being larger in those exhibiting higher diversity compared to those with lower diversity. Moreover, the PRS effects were larger in individuals with a high abundance of the genera Romboutsia, Streptococcus, and Anaerostipes than in those with low abundance (p < 0.05). All three of these genera showed protective effects against SCZ. Conclusion: The current findings suggest an interplay between the gut microbiota and polygenic risk of SCZ that warrants replication in independent samples. Experimental studies are needed to determine the underpinning mechanisms.

Multiomics Analyses Reveal Microbiome-Gut-Brain Crosstalk Centered on Aberrant Gamma-Aminobutyric Acid and Tryptophan Metabolism in Drug-Naïve Patients with First-Episode Schizophrenia.

BACKGROUND AND HYPOTHESIS: Schizophrenia (SCZ) is associated with complex crosstalk between the gut microbiota and host metabolism, but the underlying mechanism remains elusive. Investigating the aberrant neurotransmitter processes reflected by alterations identified using multiomics analysis is valuable to fully explain the pathogenesis of SCZ. STUDY DESIGN: We conducted an integrative analysis of multiomics data, including the serum metabolome, fecal metagenome, single nucleotide polymorphism data, and neuroimaging data obtained from a cohort of 127 drug-naïve, first-episode SCZ patients and 92 healthy controls to characterize the microbiome-gut-brain axis in SCZ patients. We used pathway-based polygenic risk score (PRS) analyses to determine the biological pathways contributing to genetic risk and mediation effect analyses to determine the important neuroimaging features. Additionally, a random forest model was generated for effective SCZ diagnosis. STUDY RESULTS: We found that the altered metabolome and dysregulated microbiome were associated with neuroactive metabolites, including gamma-aminobutyric acid (GABA), tryptophan, and short-chain fatty acids. Further structural and functional magnetic resonance imaging analyses highlighted that gray matter volume and functional connectivity disturbances mediate the relationships between Ruminococcus_torgues and Collinsella_aerofaciens and symptom severity and the relationships between species Lactobacillus_ruminis and differential metabolites l-2,4-diaminobutyric acid and N-acetylserotonin and cognitive function. Moreover, analyses of the Polygenic Risk Score (PRS) support that alterations in GABA and tryptophan neurotransmitter pathways are associated with SCZ risk, and GABA might be a more dominant contributor. CONCLUSIONS: This study provides new insights into systematic relationships among genes, metabolism, and the gut microbiota that affect brain functional connectivity, thereby affecting SCZ pathogenesis.

Engrailed 2 serves as a master regulator of the super-enhancer in the TNC gene locus in non-small cell lung cancer.

Engrailed 2 (EN2) is a homeodomain-containing protein that is dysregulated in many types of cancer. However, the role of EN2 in non-small cell lung cancer (NSCLC) and the mechanism underlying its biological function are largely unclear. Here, we showed that EN2 played an oncogenic function in NSCLC and greatly enhanced the malignant phenotype of NSCLC cells. Meanwhile, EN2 was able to boost the expression of a well-studied oncogenic Tenascin-C (TNC) gene, which in turn activated the AKT signaling pathway. Interestingly, we found that EN2 directly bound to the super-enhancer (SE) region in the TNC locus. The histone marker H3K27ac was also enriched in the region, indicating the activation of the SE. Treatment of the cells with JQ1, an inhibitor of SE activity, abrogated the effect of EN2 on the expression of TNC and phosphorylation of AKT-Ser473. Collectively, our work unveils a novel mode of EN2 function, in which EN2 governs the SE in the TNC locus, consequently activating the oncogenic TNC-AKT axis in NSCLC.

Correlation between cognitive impairment and metabolic imbalance of gut microbiota in patients with schizophrenia.

BACKGROUND: The gut microbiome interacts with the central nervous system through the gut-brain axis, and this interaction involves neuronal, endocrine, and immune mechanisms, among others, which allow the microbiota to influence and respond to a variety of behavioral and mental conditions. AIM: To explore the correlation between cognitive impairment and gut microbiota imbalance in patients with schizophrenia. METHODS: A total of 498 untreated patients with schizophrenia admitted to our hospital from July 2020 to July 2022 were selected as the case group, while 498 healthy volunteers who underwent physical examinations at our hospital during the same period were selected as a control group. Fluorescence in situ hybridization was employed to determine the total number of bacteria in the feces of the two groups. The cognitive function test package was used to assess the score of cognitive function in each dimension. Then, the relationship between gut microbiota and cognitive function was analyzed. RESULTS: There were statistically significant differences in the relative abundance of gut microbiota at both phylum and class levels between the case group and the control group. In addition, the scores of cognitive function, such as atten-tion/alertness and learning ability, were significantly lower in the case group than in the control group (all P < 0.05). The cognitive function was positively correlated with Actinomycetota, Bacteroidota, Euryarchaeota, Fusobacteria, Pseudomonadota, and Saccharibacteria, while negatively correlated with Bacillota, Tenericutes, and Verrucomicrobia at the phylum level. While at the class level, the cognitive function was positively correlated with Class Actinobacteria, Bacteroidia, Betaproteobacteria, Proteobacteria, Blastomycetes, and Gammaproteobacteria, while negatively correlated with Bacilli, Clostridia, Coriobacteriia, and Verrucomicrobiae. CONCLUSION: There is a relationship between the metabolic results of gut microbiota and cognitive function in patients with schizophrenia. When imbalances occur in the gut microbiota of patients, it leads to more severe cognitive impairment.

Multi-loss Disentangled Generative-Discriminative Learning for Multimodal Representation in Schizophrenia.

Schizophrenia (SCZ) is a multifactorial mental illness, thus it will be beneficial for exploring this disease using multimodal data, including functional magnetic resonance imaging (fMRI), genes, and the gut microbiome. Previous studies reported combining multimodal data can offer complementary information for better depicting the abnormalities of SCZ. However, the existing multimodal-based methods have multiple limitations. First, most approaches cannot fully use the relationships among different modalities for the downstream tasks. Second, representing multimodal data by the modality-common and modality-specific components can improve the performance of multimodal analysis but often be ignored. Third, most methods conduct the model for classification or regression, thus a unified model is needed for finishing these tasks simultaneously. To this end, a multi-loss disentangled generative-discriminative learning (MDGDL) model was developed to tackle these issues. Specifically, using disentangled learning method, the genes and gut microbial biomarkers were represented and separated into two modality-specific vectors and one modality-common vector. Then, a generative-discriminative framework was introduced to uncover the relationships between fMRI features and these three latent vectors, further producing the attentive vectors, which can help fMRI features for the downstream tasks. To validate the performance of MDGDL, an SCZ classification task and a cognitive score regression task were conducted. Results showed the MDGDL achieved superior performance and identified the most important multimodal biomarkers for the SCZ. Our proposed model could be a supplementary approach for multimodal data analysis. Based on this method, we could analyze the SCZ by combining multimodal data, and further obtain some interesting findings.

A lanthanide luminescent sensor for the detection of 4-nitrophenol in aqueous media.

The development of facile luminescent sensors for detecting nitrophenols in aqueous media is of great necessity for the safety of the environment and human health, as they are a class of widespread toxic organic pollutants that cause serious adverse effects upon consumption. Based on a new multidentate asymmetric ligand (H2L) in which salicylamide and 4-nitryl-salicylaldimine are spaced by 1,2-bis(2-ethoxy)ethyl, a new hydrostable lanthanide intercycle, [Tb2L2(NO3)2]·CH3CN (Tb-[2]c), was prepared to act as a new luminescent sensor for 4-NP in water media. Structural analysis indicated that two fully deprotonated L2- ligands in cis-configuration and µ2-L-κ2O1:κO2:κO4:κN2:κO5 coordination mode were interlocked by two TbIII ions to render the emitted TbIII encapsulated by L2- for lessening non-radiative transitions. The excellent sensitizing capability of the ligand L2- to TbIII was ascertained by both experimental methods and theoretical calculations. The sensing exploration indicated that Tb-[2]c exhibited highly sensitive and selective recognition of 4-NP against other nitroaromatics in aqueous media. The recognition mechanism could be attributed to the internal filtration effect (IFE) mechanism when DFT calculations and accumulating experimental evidence were combined.

Engrailed 2 triggers the activation of multiple phosphorylation-induced signaling pathways in both transcription-dependent and -independent manners.

Homeodomain (HD)-containing proteins are typically recognized as transcription factors. Engrailed 2 (EN2) is an HD-containing protein that is highly expressed in various types of cancers, however, the mechanism underlying the biological function of EN2 is not fully understood. Here, we report a transcription-independent function of EN2 in addition to its role as a transcription factor. EN2 expression leads to the activation of multiple signaling pathways mediated by phosphorylation cascades. A phosphoproteomic analysis revealed that the phosphorylation status of numerous protein sites was altered after EN2 is expressed. Notably, EN2 was shown to interact with a myriad of proteins implicated in phosphorylation signaling cascades, as determined by immunoprecipitation-mass spectrometry (IP-MS). We validated the interaction between EN2 and B55α, the regulatory subunit of the PP2A-B55α complex, and confirmed that the phosphatase activity of the complex was suppressed by EN2 binding. To target EN2-induced malignancy, two kinds of small molecules were utilized to inhibit the EN2-activated NF-κB and AKT signaling pathways. A clear synergistic effect was observed when the activation of the two pathways was simultaneously blocked. Collectively, the data show that EN2 functions in a transcription-independent manner in addition to its role as a transcription factor. This finding may have therapeutic implications in treating esophageal squamous cell carcinoma (ESCC).

Microglia and cognitive impairment in schizophrenia: translating scientific progress into novel therapeutic interventions.

Cognitive impairment is a core clinical feature of schizophrenia, exerting profound adverse effects on social functioning and quality of life in a large proportion of patients with schizophrenia. However, the mechanisms underlying the pathogenesis of schizophrenia-related cognitive impairment are not well understood. Microglia, the primary resident macrophages in the brain, have been shown to play important roles in psychiatric disorders, including schizophrenia. Increasing evidence has revealed excessive microglial activation in cognitive deficits related to a broad range of diseases and medical conditions. Relative to that about age-related cognitive deficits, current knowledge about the roles of microglia in cognitive impairment in neuropsychiatric disorders, such as schizophrenia, is limited, and such research is in its infancy. Thus, we conducted this review of the scientific literature with a focus on the role of microglia in schizophrenia-associated cognitive impairment, aiming to gain insight into the roles of microglial activation in the onset and progression of such impairment and to consider how scientific advances could be translated to preventive and therapeutic interventions. Research has demonstrated that microglia, especially those in the gray matter of the brain, are activated in schizophrenia. Upon activation, microglia release key proinflammatory cytokines and free radicals, which are well-recognized neurotoxic factors contributing to cognitive decline. Thus, we propose that the inhibition of microglial activation holds potential for the prevention and treatment of cognitive deficits in patients with schizophrenia. This review identifies potential targets for the development of new treatment strategies and eventually the improvement of care for these patients. It might also help psychologists and clinical investigators in planning future research.

Comprehensive analysis of m6A regulators characterized by the immune microenvironment in Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked, incurable, degenerative neuromuscular disease that is exacerbated by secondary inflammation. N6-methyladenosine (m6A), the most common base modification of RNA, has pleiotropic immunomodulatory effects in many diseases. However, the role of m6A modification in the immune microenvironment of DMD remains elusive. METHODS: Our study retrospectively analyzed the expression data of 56 muscle tissues from DMD patients and 26 from non-muscular dystrophy individuals. Based on single sample gene set enrichment analysis, immune cells infiltration was identified and the result was validated by flow cytometry analysis and immunohistochemical staining. Then, we described the features of genetic variation in 26 m6A regulators and explored their relationship with the immune mircoenvironment of DMD patients through a series of bioinformatical analysis. At last, we determined subtypes of DMD patients by unsupervised clustering analysis and characterized the molecular and immune characteristics in different subgroups. RESULTS: DMD patients have a sophisticated immune microenvironment that is significantly different from non-DMD controls. Numerous m6A regulators were aberrantly expressed in the muscle tissues of DMD and inversely related to most muscle-infiltrating immune cell types and immune response-related signaling pathways. A diagnostic model involving seven m6A regulators was established using LASSO. Furthermore, we determined three m6A modification patterns (cluster A/B/C) with distinct immune microenvironmental characteristics. CONCLUSION: In summary, our study demonstrated that m6A regulators are intimately linked to the immune microenvironment of muscle tissues in DMD. These findings may facilitate a better understanding of the immunomodulatory mechanisms in DMD and provide novel strategies for the treatment.

Early non-response as a predictor of later non-response to antipsychotics in schizophrenia: a randomized trial.

BACKGROUND: It remains a challenge to predict the long-term response to antipsychotics in patients with schizophrenia who do not respond at an early stage. This study aimed to investigate the optimal predictive cut-off value for early non-response that would better predict later non-response to antipsychotics in patients with schizophrenia. METHODS: This multicenter, 8-week, open-label, randomized trial was conducted at 19 psychiatric centers throughout China. All enrolled participants were assigned to olanzapine, risperidone, amisulpride, or aripiprazole monotherapy for 8 weeks. The positive and negative syndrome scale (PANSS) was evaluated at baseline, week 2, week 4, and week 8. The main outcome was the prediction of nonresponse. Nonresponse is defined as a < 20% reduction in the total scores of PANSS from baseline to endpoint. Severity ratings of mild, moderate, and severe illness corresponded to baseline PANSS total scores of 58, 75, and 95, respectively. RESULTS: At week 2, a reduction of < 5% in the PANSS total score showed the highest total accuracy in the severe and mild schizophrenia patients (total accuracy, 75.0% and 80.8%, respectively), and patients who were treated with the risperidone and amisulpride groups (total accuracy, 82.4%, and 78.2%, respectively). A 10% decrease exhibited the best overall accuracy in the moderate schizophrenia patients (total accuracy, 84.0%), olanzapine (total accuracy, 79.2%), and aripiprazole group (total accuracy, 77.4%). At week 4, the best predictive cut-off value was < 20%, regardless of the antipsychotic or severity of illness (total accuracy ranging from 89.8 to 92.1%). CONCLUSIONS: Symptom reduction at week 2 has acceptable discrimination in predicting later non-response to antipsychotics in schizophrenia, and a more accurate predictive cut-off value should be determined according to the medication regimen and baseline illness severity. The response to treatment during the next 2 weeks after week 2 could be further assessed to determine whether there is a need to change antipsychotic medication during the first four weeks. TRIAL REGISTRATION: This study was registered on Clinicaltrials.gov (NCT03451734).

A method for analyzing programmed cell death in xylem development by flow cytometry.

Programmed cell death (PCD) is a genetically regulated developmental process leading to the death of specific types of plant cells, which plays important roles in plant development and growth such as wood formation. However, an efficient method needs to be established to study PCD in woody plants. Flow cytometry is widely utilized to evaluate apoptosis in mammalian cells, while it is rarely used to detect PCD in plants, especially in woody plants. Here, we reported that the xylem cell protoplasts from poplar stem were stained with a combination of fluorescein annexin V-FITC and propidium iodide (PI) and then sorted by flow cytometry. As expected, living cells (annexin V-FITC negative/PI negative), early PCD cells (annexin V-FITC positive/PI negative), and late PCD cells (annexin V-FITC positive/PI positive) could be finely distinguished through this method and then subjected for quantitative analysis. The expression of cell-type- and developmental stages-specific marker genes was consistent with the cell morphological observation. Therefore, the newly developed fluorescence-activated cell sorting (FACS) method can be used to study PCD in woody plants, which will be beneficial for studying the molecular mechanisms of wood formation.

Impaired large-scale cortico-hippocampal network connectivity, including the anterior temporal and posterior medial systems, and its associations with cognition in patients with first-episode schizophrenia.

Background and objective: The cortico-hippocampal network is an emerging neural framework with striking evidence that it supports cognition in humans, especially memory; this network includes the anterior temporal (AT) system, the posterior medial (PM) system, the anterior hippocampus (aHIPPO), and the posterior hippocampus (pHIPPO). This study aimed to detect aberrant patterns of functional connectivity within and between large-scale cortico-hippocampal networks in first-episode schizophrenia patients compared with a healthy control group via resting-state functional magnetic resonance imaging (rs-fMRI) and to explore the correlations of these aberrant patterns with cognition. Methods: A total of 86 first-episode, drug-naïve schizophrenia patients and 102 healthy controls (HC) were recruited to undergo rs-fMRI examinations and clinical evaluations. We conducted large-scale edge-based network analysis to characterize the functional architecture of the cortico-hippocampus network and investigate between-group differences in within/between-network functional connectivity. Additionally, we explored the associations of functional connectivity (FC) abnormalities with clinical characteristics, including scores on the Positive and Negative Syndrome Scale (PANSS) and cognitive scores. Results: Compared with the HC group, schizophrenia patients exhibited widespread alterations to within-network FC of the cortico-hippocampal network, with decreases in FC involving the precuneus (PREC), amygdala (AMYG), parahippocampal cortex (PHC), orbitofrontal cortex (OFC), perirhinal cortex (PRC), retrosplenial cortex (RSC), posterior cingulate cortex (PCC), angular gyrus (ANG), aHIPPO, and pHIPPO. Schizophrenia patients also showed abnormalities in large-scale between-network FC of the cortico-hippocampal network, in the form of significantly decreased FC between the AT and the PM, the AT and the aHIPPO, the PM and the aHIPPO, and the aHIPPO and the pHIPPO. A number of these signatures of aberrant FC were correlated with PANSS score (positive, negative, and total score) and with scores on cognitive test battery items, including attention/vigilance (AV), working memory (WM), verbal learning and memory (Verb_Lrng), visual learning and memory (Vis_Lrng), reasoning and problem-solving (RPS), and social cognition (SC). Conclusion: Schizophrenia patients show distinct patterns of functional integration and separation both within and between large-scale cortico-hippocampal networks, reflecting a network imbalance of the hippocampal long axis with the AT and PM systems, which regulate cognitive domains (mainly Vis_Lrng, Verb_Lrng, WM, and RPS), and particularly involving alterations to FC of the AT system and the aHIPPO. These findings provide new insights into the neurofunctional markers of schizophrenia.

Low-dose lithium mono- and adjunctive therapies improve MK-801-induced cognitive impairment and schizophrenia-like behavior in mice - Evidence from altered prefrontal lobe Ca2+ activity.

BACKGROUND: Few studies have evaluated lithium either as monotherapy or in combination with anti-psychotic agents to improve cognition in murine models of schizophrenia. METHODS: Visualization of Ca2+ activity in the prefrontal cortex was used to characterize brain neural activity. Novel object recognition (NOR), Morris water maze (MWM), and fear conditioning (FCT) tests were used to characterize cognitive performance; while pre-pulse inhibition (PPI), elevated plus maze (EPM) and the open field test (OFT) were used to characterize schizophrenia-like behavior. RESULTS: A 28-day course of low-dose lithium (human equivalent dose of 250 mg/day) combined with moderate-dose quetiapine (human equivalent dose of 600 mg/day) improved Ca2+ ratio by 70.10 %, PPI by 69.28 %, NOR by 70.09 %, MWM by 71.28 %, FCT by 68.56 %, EPM by 70.95 % and OFT by 75.23 % compared to the results of positive controls. Unexpectedly, moderate-dose lithium (human equivalent dose of 500 mg/day) used either as monotherapy or as an adjunct with quetiapine worsened Ca2+ activity, PPI, MWM, FCT, EPM, and OPT. LIMITATIONS: Our study cannot explain the contrasting positive and negative effects of low-dose and moderate-dose lithium, respectively, when used either as monotherapies or as adjuncts. Further studies, especially Western blotting, may reveal molecular mechanisms of action. CONCLUSIONS: Low-dose lithium (human equivalent dose of 250 mg/day) combined with moderate-dose quetiapine (human equivalent dose of 600 mg/day) provided the best improvements. Furthermore, benefits persisted for 14 days post-treatment. Our data provide directions for further research of therapeutic alternatives to mitigate schizophrenia-related cognopathy.

Oxidative stress impairs cognitive function by affecting hippocampal fimbria volume in drug-naïve, first-episode schizophrenia.

Objective: The aim of the present study was to explore influencing factors of cognitive impairments and their interrelationships in drug-naïve, first-episode schizophrenia (SCZ). Methods: Patients with drug naïve, first episode SCZ and healthy controls (HCs) were enrolled. Cognitive function was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Serum levels of oxidative stress indices, including folate, superoxide dismutase (SOD), uric acid (UA) and homocysteine (Hcy), were determined after an overnight fast. Hippocampal subfield volumes were measured using FreeSurfer. Mediation models were conducted using the SPSS PROCESS v3.4 macro. A false discovery rate (FDR) correction was applied for multiple comparisons. Results: Sixty-seven patients with SCZ and 65 HCs were enrolled in our study. The patient group had significantly lower serum levels of folate and SOD and higher serum levels of HCY compared with the HCs (all p < 0.05). The patient group had a significantly smaller volume of the whole hippocampus than the HC group (p < 0.05). We also found significant volume differences between the two groups in the following subfields: CA1, molecular layer, GC-ML-DG and fimbria (all p < 0.05, uncorrected). The partial correlation analysis controlling for age and sex showed that the fimbria volume in the patient group was significantly positively associated with NAB scores (r = 0.382, pFDR = 0.024); serum levels of SOD in the patient group showed a significantly positive correlation with fimbria volume (r = 0.360, pFDR = 0.036). Mediation analyses controlling for age and sex showed that the serum levels of SOD in patients with SCZ had significant indirect effects on the NAB scores which were mediated by the fimbria volume [indirect effect = 0.0565, 95% CI from the bootstrap test excluding zero (0.0066 to 0.0891)]. Conclusion: Oxidative stress, a reduction in hippocampal subfield volumes and cognitive impairments occur in early SCZ. Oxidative stress impairs cognitive function by affecting hippocampal subfield volumes.