The role of the immune system in early-onset schizophrenia: identifying immune characteristic genes and cells from peripheral blood.

BACKGROUND: Early-onset schizophrenia (EOS) is a type of schizophrenia (SCZ) with an age of onset of < 18 years. An abnormal inflammatory immune system may be involved in the occurrence and development of SCZ. We aimed to identify the immune characteristic genes and cells involved in EOS and to further explore the pathogenesis of EOS from the perspective of immunology. METHODS: We obtained microarray data from a whole-genome mRNA expression in peripheral blood mononuclear cells (PBMCs); 19 patients with EOS (age range: 14.79 ± 1.90) and 18 healthy controls (HC) (age range: 15.67 ± 2.40) were involved. We screened for differentially expressed genes (DEGs) using the Limma software package and modular genes using weighted gene co-expression network analysis (WGCNA). In addition, to identify immune characteristic genes and cells, we performed enrichment analysis, immune infiltration analysis, and receiver operating characteristic (ROC) curve analysis; we also used a random forest (RF), a support vector machine (SVM), and the LASSO-Cox algorithm. RESULTS: We selected the following immune characteristic genes: CCL8, PSMD1, AVPR1B and SEMG1. We employed a RF, a SVM, and the LASSO-Cox algorithm. We identified the following immune characteristic cells: activated mast cells, CD4+ memory resting T cells, resting mast cells, neutrophils and CD4+ memory activated T cells. In addition, the AUC values of the immune characteristic genes and cells were all > 0.7. CONCLUSION: Our results indicate that immune system function is altered in SCZ. In addition, CCL8, PSMD1, AVPR1B and SEMG1 may regulate peripheral immune cells in EOS. Further, immune characteristic genes and cells are expected to be diagnostic markers and therapeutic targets of SCZ.

Plasma levels of hydrogen sulfide and homocysteine correlate with the efficacy of antidepressant agents and serve as potential diagnostic and therapeutic markers.

OBJECTIVE: Hydrogen sulfide (H2S) is associated with depressive-like behavior in rodents. We undertook cross-sectional and longitudinal analyses of plasma levels of H2S and its substrate homocysteine (Hcy) in depression and assessed the association of both parameters with psychopathology and cognitive function. METHODS: Forty-one patients suffering from depression (PSDs) and 48 healthy volunteers were recruited. PSDs were treated for 8 weeks. Analyzable data were collected from all participants for assessment of their psychopathology and cognitive function. Plasma was collected for determination of levels of H2S and Hcy, and data were correlated to determine their potential as plasma biomarkers. RESULTS: Cross-sectional analyses revealed PSDs to have a low plasma H2S level and high Hcy level. Longitudinal analyses revealed that 8 weeks of treatment reversed the changes in plasma levels of H2S and Hcy in PSDs. Plasma levels of H2S and Hcy were associated with psychopathology and cognitive function in depression. The area under the receiver operating characteristic curve (AUC) for a combination of plasma levels of H2S and Hcy and expression of the TNF gene (i.e., H2S-Hcy-TNF) was 0.848 for diagnosing depression and 0.977 for predicting the efficacy of antidepressant agents. CONCLUSION: Plasma levels of H2S and Hcy reflect changes in psychopathology and cognitive function in depression and H2S-Hcy-TNF has the potential to diagnose depression and predict the efficacy of antidepressant medications.

m6A facilitates hippocampus-dependent learning and memory through YTHDF1.

N6-methyladenosine (m6A), the most prevalent internal RNA modification on mammalian messenger RNAs, regulates the fates and functions of modified transcripts through m6A-specific binding proteins1-5. In the nervous system, m6A is abundant and modulates various neural functions6-11. Whereas m6A marks groups of mRNAs for coordinated degradation in various physiological processes12-15, the relevance of m6A for mRNA translation in vivo remains largely unknown. Here we show that, through its binding protein YTHDF1, m6A promotes protein translation of target transcripts in response to neuronal stimuli in the adult mouse hippocampus, thereby facilitating learning and memory. Mice with genetic deletion of Ythdf1 show learning and memory defects as well as impaired hippocampal synaptic transmission and long-term potentiation. Re-expression of YTHDF1 in the hippocampus of adult Ythdf1-knockout mice rescues the behavioural and synaptic defects, whereas hippocampus-specific acute knockdown of Ythdf1 or Mettl3, which encodes the catalytic component of the m6A methyltransferase complex, recapitulates the hippocampal deficiency. Transcriptome-wide mapping of YTHDF1-binding sites and m6A sites on hippocampal mRNAs identified key neuronal genes. Nascent protein labelling and tether reporter assays in hippocampal neurons showed that YTHDF1 enhances protein synthesis in a neuronal-stimulus-dependent manner. In summary, YTHDF1 facilitates translation of m6A-methylated neuronal mRNAs in response to neuronal stimulation, and this process contributes to learning and memory.

Factors affecting the readiness for hospital discharge of initially treated pulmonary tuberculosis patients in China: a phenomenological study.

BACKGROUND: Despite readiness for hospital discharge widespread popularity since readiness for hospital discharge introduction in 1979 and extensive study, readiness for hospital discharge among pulmonary tuberculosis (PTB) patients has not yet been investigated. Moreover, the factors influencing this process remain unclear. OBJECTIVE: The objective of this study was to investigate the factors influencing readiness for hospital discharge in initially treated PTB patients using the capability, opportunity, motivation-behavior (COM-B) model. METHODS: This phenomenological study was conducted from December 2023 to March 2024. Face-to-face individual interviews were conducted with 18 initially treated patients with PTB according to a semistructured interview guide developed on the basis of the COM-B model. The interview data were subjected to analysis using NVivo 14 software and Colaizzi's method. RESULTS: As a result, 6 themes and 14 subthemes were identified. Physical capability for readiness for hospital discharge (subthemes included poor health status, early acquisition of adequate knowledge about PTB, inadequate knowledge about readiness for hospital discharge), psychological capability for readiness for hospital discharge(subthemes included false perceptions about readiness for hospital discharge, high treatment adherence), physical opportunity for readiness for hospital discharge (subthemes included high continuity of transition healthcare, insufficient financial support, insufficient informational support), social opportunity for readiness for hospital discharge (subthemes included stigmatization, inadequate emotional support), reflective motivation for readiness for hospital discharge (subthemes included lack of reflection on coping with difficulties, intention to develop a readiness for hospital discharge plan), and automatic motivation for readiness for hospital discharge (subthemes included strong desire to be cured, negative emotions). CONCLUSION: We established factors related to readiness for hospital discharge in initially treated PTB patients in terms of capability, opportunity and motivation, which can inform the future development of readiness for hospital discharge plans. To improve patients' readiness for hospital discharge, patients need to be motivated to plan and desire readiness for hospital discharge, patients' knowledge and treatment adherence should be improved, and patients' transition healthcare continuity and emotional support should be focused on. Moreover, the quality of readiness for hospital discharge and discharge education should be assessed in a timely manner to identify impeding factors and provide interventions.

Modifying the Charge-Density of Tetrahedral Cobalt(II) Centers through Carbon-Layer Modulation Promotes C-H Activation in the Propane Dehydrogenation Reaction (PDH).

The electronic structure of active metal centers plays an indispensable role in regulating catalytic reactivity in heterogeneous catalysis, developing other metals as promoters to decorate electronic state is a common strategy, while non-metal component of carbon as electronic additives to regulate d-band center has rarely been studied in thermal-catalysis field. Herein, we report electron-deficient tetrahedral Co(II) (Td-cobalt(II)) centers through carbon-layer modulation for propane dehydrogenation (PDH). It is indicated that bifunctional sites of both Td-cobalt(II) and metallic-cobalt are designed, and the in situ generated carbon through the disproportionation of CO on metallic-cobalt can cover the inactive metallic-cobalt and tailor d-band of active Td-cobalt(II) simultaneously. More importantly, the pre-deposited carbon-layer is proposed to decrease electron density of Td-cobalt(II) and make d-band center closer to Fermi level, consequently promotes C-H activation in PDH reaction. This study provides new perspective for the utilization of inactive carbon as electronic promoters and unlocks new opportunity to fabricate efficient PDH and other heterogeneous catalysts.

Plasma exosomes lncRNA-miRNA-mRNA network construction and its diagnostic efficacy identification in first-episode schizophrenia.

BACKGROUND: The exosomal lncRNA-miRNA-mRNA networks in first episode schizophrenia (FOS) have not reported yet. This study examined the lncRNA, miRNA and mRNA expression level in exosome derived from first episode schizophrenia (FOS) patients, and explored the the potential of exosomes as biomarkers for schizophrenia. METHODS: We recruited 10 FOS patients and healthy controls (HCs) respectively, examined the lncRNA, miRNA and mRNA expression level of plasma exosome by high throughput sequencing, constructed lncRNA-miRNA-mRNA network, and performed correlation analysis, GO and KEGG pathway analysis, PPI network construction and ROC analysis. RESULTS: There were 746 differently expressed lncRNA, 22 differently expressed miRNA, and 2637 differently expressed mRNA in plasma exosome in FOS compared with HCs. Then we constructed ceRNA network consisting of 8 down-regulated lncRNA, 7 up-regulated miRNA and 65 down-regulated mRNA, and 1 up-regulated lncRNA, 1 down-regulated miRNA and 4 up-regulated mRNA. The expression level of 1 lncRNA and 7 mRNA in exosomal network were correlated with PANSS score. GO and KEGG pathway analysis showed that 4 up-regulated mRNAs were enriched in neuropsychiatric system function. Down-regulated mRNA EZH2 and SIRT1 were identified as hub gene. Finally, we detected the ROC curve of ENSG00000251562, miR-26a-5p, EZH2, miR-22-3p, SIRT1, ENSG00000251562-miR-26a-5p-EZH2, ENSG00000251562-miR-22-3p-SIRT1, and found that the AUC of ceRNA network was higher than lncRNA, miRNA and mRNA alone. CONCLUSION: We constructed the lncRNA-miRNA-mRNA network in exosome derived from FOS plasma, and found that lncRNA-miRNA-mRNA network has potential as biomarkers for FOS.

The development of processing second-order spatial relations of faces in Chinese preschoolers.

Second-order relational information processing is the perception of the relative distance between facial features. Previous studies ignored the effect of different spatial manipulations on second-order sensitivity in face processing, and little is known about its developmental trajectory in East Asian populations, who have stronger holistic face processing than Western populations. We addressed these gaps in the literature through an experiment with four groups of Chinese preschool children (aged 3-6 years; n = 157) and a group of adults (n = 25). The participants were presented with face pairs displaying features with various spatial distance manipulations (Change 1: changes in the spacing between eyes; Change 2: nose-mouth spacing changes; Change 3: a combination of Changes 1 and 2) using a simultaneous two-alternative forced-choice task. Second-order sensitivity was already present in 3-year-old children across all manipulations and became more pronounced in 4-year-old children. Second-order sensitivity to the spatial distance between the eyes (i.e., Changes 1 and 3) among 4-year-olds was higher than that of 3-year-olds and was similar to that of adults, suggesting a key increase of this sensitivity from 3 to 4 years of age. Regarding the Change 2 condition, preschoolers aged 5 and 6 years had higher sensitivity than 3-year-olds; however, all preschoolers' sensitivity was inferior to that of adults. These findings show that the development of Chinese preschoolers' sensitivity for detecting spatial relations between the eyes might be faster than that for detecting nose-mouth spacing, supporting the importance of eyes in face processing.

Porous organic polymers as a platform for sensing applications.

Sensing analysis is significantly important for human health and environmental safety, and has gained increasing concern. As a promising material, porous organic polymers (POPs) have drawn widespread attention due to the availability of plentiful building blocks and their tunable structures, porosity and functions. Moreover, the permanent porous nature could provide a micro-environment to interact with guest molecules, rendering POPs attractive for application in the sensing field. In this review, we give a comprehensive overview of POPs as a platform for sensing applications. POP-based sensors are mainly divided into five categories, including fluorescence turn-on sensors, fluorescence turn-off sensors, ratiometric fluorescent sensors, colorimetric sensors and chemiresistive sensors, and their various sensing applications in detecting explosives, metal ions, anions, small molecules, biological molecules, pH changes, enantiomers, latent fingerprints and thermosensation are summarized. The different structure-based POPs and their corresponding synthetic strategies as well as the related sensing mechanisms mainly including energy transfer, donor-acceptor electron transfer, absorption competition quenching and inner filter effect are also involved in the discussion. Finally, the future outlook and perspective are addressed briefly.

H3K36 methylation promotes longevity by enhancing transcriptional fidelity.

Epigenetic mechanisms, including histone post-translational modifications, control longevity in diverse organisms. Relatedly, loss of proper transcriptional regulation on a global scale is an emerging phenomenon of shortened life span, but the specific mechanisms linking these observations remain to be uncovered. Here, we describe a life span screen in Saccharomyces cerevisiae that is designed to identify amino acid residues of histones that regulate yeast replicative aging. Our results reveal that lack of sustained histone H3K36 methylation is commensurate with increased cryptic transcription in a subset of genes in old cells and with shorter life span. In contrast, deletion of the K36me2/3 demethylase Rph1 increases H3K36me3 within these genes, suppresses cryptic transcript initiation, and extends life span. We show that this aging phenomenon is conserved, as cryptic transcription also increases in old worms. We propose that epigenetic misregulation in aging cells leads to loss of transcriptional precision that is detrimental to life span, and, importantly, this acceleration in aging can be reversed by restoring transcriptional fidelity.

Construction of Single-Atom Catalysts for N, O Synergistic Coordination and Application to Electrocatalytic O2 Reduction.

Replacing expensive platinum oxygen reduction reaction (ORR) catalysts with atomically dispersed single-atom catalysts is an effective way to improve the energy conversion efficiency of fuel cells. Herein, a series of single-atom catalysts, TM-N2O2Cx (TM=Sc-Zn) with TM-N2O2 active units, were designed, and their catalytic performance for electrocatalytic O2 reduction was investigated based on density functional theory. The results show that TM-N2O2Cx exhibits excellent catalytic activity and stability in acidic media. The eight catalysts (TM=Sc, Ti, V, Cr, Mn, Fe, Co, and Ni) are all 4e- reaction paths, among which Sc-N2O2Cx, Ti-N2O2Cx, and V-N2O2Cx follow dissociative mechanisms and the rest are consistent with associative mechanisms. In particular, Co-N2O2Cx and Ni-N2O2Cx enable a smooth reduction in O2 at small overpotentials (0.44 V and 0.49 V, respectively). Furthermore, a linear relationship between the adsorption free energies of the ORR oxygen-containing intermediates was evident, leading to the development of a volcano plot for the purpose of screening exceptional catalysts for ORR. This research will offer a novel strategy for the design and fabrication of exceptionally efficient non-precious metal catalysts on an atomic scale.

The role of Class â ¡ KNOX family in controlling compound leaf patterning in Medicago truncatula.

Compound leaf development requires the coordination of genetic factors, hormones, and other signals. In this study, we explored the functions of Class Ⅱ KNOTTED-like homeobox (KNOXII) genes in the model leguminous plant Medicago truncatula. Phenotypic and genetic analyses suggest that MtKNOX4, 5 are able to repress leaflet formation, while MtKNOX3, 9, 10 are not involved in this developmental process. Further investigations have shown that MtKNOX4 represses the CK signal transduction, which is downstream of MtKNOXⅠ-mediated CK biosynthesis. Additionally, two boundary genes, FUSED COMPOUND LEAF1 (orthologue of Arabidopsis Class M KNOX) and NO APICAL MERISTEM (orthologue of Arabidopsis CUP-SHAPED COTYLEDON), are necessary for MtKNOX4-mediated compound leaf formation. These findings suggest, that among the members of MtKNOXⅡ, MtKNOX4 plays a crucial role in integrating the CK pathway and boundary regulators, providing new insights into the roles of MtKNOXⅡ in regulating the elaboration of compound leaves in M. truncatula.

Profiling of Urine Carbonyl Metabolic Fingerprints in Bladder Cancer Based on Ambient Ionization Mass Spectrometry.

The diagnosis of bladder cancer (BC) is currently based on cystoscopy, which is invasive and expensive. Here, we describe a noninvasive profiling method for carbonyl metabolic fingerprints in BC, which is based on a desorption, separation, and ionization mass spectrometry (DSI-MS) platform with N,N-dimethylethylenediamine (DMED) as a differential labeling reagent. The DSI-MS platform avoids the interferences from intra- and/or intersamples. Additionally, the DMED derivatization increases detection sensitivity and distinguishes carboxyl, aldehyde, and ketone groups in untreated urine samples. Carbonyl metabolic fingerprints of urine from 41 BC patients and 41 controls were portrayed and 9 potential biomarkers were identified. The mechanisms of the regulations of these biomarkers have been tentatively discussed. A logistic regression (LR) machine learning algorithm was applied to discriminate BC from controls, and an accuracy of 85% was achieved. We believe that the method proposed here may pave the way toward the point-of-care diagnosis of BC in a patient-friendly manner.

Laser Desorption/Ionization Mass Spectrometry Imaging: A New Tool to See through Nanoscale Particles in Biological Systems.

Understanding the fate of nanoscale particles (NPs) in biological systems is significant with the increasing risk for human exposure. Recent research endeavors in laser desorption/ionization mass spectrometry imaging (LDI-MSI) have enriched the toolbox for evaluation of NPs' behavior in biological tissues, especially in aspects including sub-organ bio-distribution, clearance, quantification and surface chemistry variation analysis. In recognition of the potential for advancement in LDI MSI, this concept provides a brief overview of recent research works in LDI MSI for NPs, illustrates new applications that demonstrate the superiority of this technique, and highlights a series of perspectives and directions to move the field forward.

Unraveling the Synergistic Reaction and the Deactivation Mechanism for the Catalytic Degradation of Double Components of Sulfur-Containing VOCs over ZSM-5-Based Materials.

The competitive adsorption behavior, the synergistic catalytic reaction, and deactivation mechanisms under double components of sulfur-containing volatile organic compounds (VOCs) are a bridge to solve their actual pollution problems. However, they are still unknown. Herein, simultaneous catalytic decomposition of methyl mercaptan (CH3SH) and ethyl mercaptan (C2H5SH) is investigated over lanthanum (La)-modified ZSM-5, and kinetic and thermodynamic results confirm a great difference in the adsorption property and catalytic transformation behavior. Meanwhile, the new synergistic reaction and deactivation mechanisms are revealed at the molecular level by combining with in situ diffuse reflectance infrared spectroscopy (in situ DRIFTS) and density functional theory (DFT) calculations. The CH3CH2* and SH* groups are presented in decomposing C2H5SH, while the new species of CH2*, active H* and S*, instead of CH3* and SH*, are proved as the key elementary groups in decomposing CH3SH. The competitive recombining of SH* in C2H5SH with highly active H* in dimethyl sulfide (CH3SCH3), an intermediate in decomposing CH3SH, would aggravate the deposition of carbon and sulfur. La/ZSM-5 exhibits potential environmental application due to the excellent stability of 200 h and water resistance. This work gives an understanding of the adsorption, catalysis, reaction, and deactivation mechanisms for decomposing double components of sulfur-containing VOCs.

Design, semi-synthesis and bioactivity evaluation of novel podophyllotoxin derivatives as potent anti-tumor agents.

In this study, a series of potential candidate molecules with excellent antitumor activity targeting tubulin and PTEN/PI3K/Akt signaling pathway was synthesized by modifying the molecule structure of podophyllotoxin (PPT) at the C-4 position via a structure-guided drug design approach. MTT assay results indicated that compound 12c had stronger anti-proliferative activities against HGC-27, MCF-7 and H460 cell lines than etoposide (VP-16), especially for HGC-27 (12c: IC50 = 0.89 ± 0.023 µM; PPT: IC50 = 6.54 ± 0.69 µM, VP-16: IC50 = 2.66 ± 0.28 µM) with lower affect in healthy human cells (293 T and GES-1). Further pharmacological analysis exhibited that 12c could bind the tubulin at the colchicine site and disrupt the dynamic equilibrium of microtubules. Moreover, 12c also suppressed the expressions/activities of matrix metalloprotease (MMP)-2, vimentin and up-regulation E-cadherin suggesting that 12c could block the epithelial-mesenchymal transition (EMT). The increased cell survival and invasion/migration were associated with the inactivation of PTEN/PI3K/Akt, 12c could regulate this pathway and cascade influence on the mitochondrial pathway, eventually, leading to the cell apoptosis. Thus, 12c may have the potential to become a candidate molecule in gastric cancer clinical treatment.

Trial of Contralateral Seventh Cervical Nerve Transfer for Spastic Arm Paralysis.

BACKGROUND: Spastic limb paralysis due to injury to a cerebral hemisphere can cause long-term disability. We investigated the effect of grafting the contralateral C7 nerve from the nonparalyzed side to the paralyzed side in patients with spastic arm paralysis due to chronic cerebral injury. METHODS: We randomly assigned 36 patients who had had unilateral arm paralysis for more than 5 years to undergo C7 nerve transfer plus rehabilitation (18 patients) or to undergo rehabilitation alone (18 patients). The primary outcome was the change from baseline to month 12 in the total score on the Fugl-Meyer upper-extremity scale (scores range from 0 to 66, with higher scores indicating better function). Results The mean increase in Fugl-Meyer score in the paralyzed arm was 17.7 in the surgery group and 2.6 in the control group (difference, 15.1; 95% confidence interval, 12.2 to 17.9; P<0.001). With regard to improvements in spasticity as measured on the Modified Ashworth Scale (an assessment of five joints, each scored from 0 to 5, with higher scores indicating more spasticity), the smallest between-group difference was in the thumb, with 6, 9, and 3 patients in the surgery group having a 2-unit improvement, a 1-unit improvement, or no change, respectively, as compared with 1, 6, and 7 patients in the control group (P=0.02). Transcranial magnetic stimulation and functional imaging showed connectivity between the ipsilateral hemisphere and the paralyzed arm. There were no significant differences from baseline to month 12 in power, tactile threshold, or two-point discrimination in the hand on the side of the donor graft. RESULTS: The mean increase in Fugl-Meyer score in the paralyzed arm was 17.7 in the surgery group and 2.6 in the control group (difference, 15.1; 95% confidence interval, 12.2 to 17.9; P<0.001). With regard to improvements in spasticity as measured on the Modified Ashworth Scale (an assessment of five joints, each scored from 0 to 5, with higher scores indicating more spasticity), the smallest between-group difference was in the thumb, with 6, 9, and 3 patients in the surgery group having a 2-unit improvement, a 1-unit improvement, or no change, respectively, as compared with 1, 6, and 7 patients in the control group (P=0.02). Transcranial magnetic stimulation and functional imaging showed connectivity between the ipsilateral hemisphere and the paralyzed arm. There were no significant differences from baseline to month 12 in power, tactile threshold, or two-point discrimination in the hand on the side of the donor graft. CONCLUSIONS: In this single-center trial involving patients who had had unilateral arm paralysis due to chronic cerebral injury for more than 5 years, transfer of the C7 nerve from the nonparalyzed side to the side of the arm that was paralyzed was associated with a greater improvement in function and reduction of spasticity than rehabilitation alone over a period of 12 months. Physiological connectivity developed between the ipsilateral cerebral hemisphere and the paralyzed hand. (Funded by the National Natural Science Foundation of China and others; Chinese Clinical Trial Registry number, 13004466 .).

State Estimation of Axisymmetric Target Based on Beacon Linear Features and View Relation.

In order to realize state estimation for axisymmetric targets and improve the accuracy and robustness of state estimation, a state estimation method for axisymmetric targets based on beacon linear features and view relation is proposed in this paper. The depth camera is used to collect the image and depth information of the object, and the features of the beacon line are extracted by the thinning process and Hough transform. Then, the rotation matrix model based on view relation is constructed to solve the target state. Finally, an axisymmetric shore power plug is taken as the experimental object and the L-V (linear features and view relation) state estimation method is compared with the C-H and C-IPPE state estimation methods. The experimental results show that the L-V state estimation method has higher accuracy and robustness.

Hydroxysafflor Yellow A Confers Neuroprotection from Focal Cerebral Ischemia by Modulating the Crosstalk Between JAK2/STAT3 and SOCS3 Signaling Pathways.

Natural bioactive compounds have increasingly proved to be promising in evidence- or target-directed treatment or modification of a spectrum of diseases including cerebral ischemic stroke. Hydroxysafflor yellow A (HSYA), a major active component of the safflower plant, has drawn more interests in recent year for its multiple pharmacological actions in the treatment of cerebrovascular and cardiovascular diseases. Although the Janus kinase signaling, such as JAK2/STAT3 pathway, has been implicated in the modulation of the disease, the inhibition or activation of the pathway that contributed to the neuronal prevention from ischemic damages remains controversial. In this study, a series of experiments were performed to examine the dose- and therapeutic time window-related pharmacological efficacies of HSYA with emphasis on the HSYA-modulated interaction of JAK2/STAT3 and SOCS3 signaling in the MCAO rats. We found that HSYA treatment significantly rescued the neurological and functional deficits in a dose-dependent manner in the MCAO rats within 3 h after ischemia. HSYA treatment with a dosage of 8 mg/kg or higher markedly downregulated the expression of the JAK2-mediated signaling that was activated in response to ischemic insult, while it also promoted the expression of SOCS3 coordinately. In the subsequent experiments with the use of the JAK2 inhibitor WP1066, we found that the treatment of WP1066 alone or combination of WP1066/HSYA all exhibited inhibitory effects on JAK2-mediated signaling, while there was no influence on the SOCS3 activity of corresponding efficacious data in the MCAO rats, suggesting that excessive activation of JAK2/STAT3 might be necessary for HSYA to provoke SOCS3-negative feedback signaling. Taking together, our study demonstrates that HSYA might modulate the crosstalk between JAK2/STAT3 and SOCS3 signaling pathways that eventually contributed to its therapeutic roles against cerebral ischemic stroke.

Regioselective Functionalization of Stable BN-Modified Luminescent Tetraphenes for High-Resolution Fingerprint Imaging.

A series of novel BN tetraphene derivatives have been prepared successfully for the first time via a post-functionalization strategy. The optical and electronic properties of these derivatives could be tuned systematically by the incorporation of different substituents on the main skeleton. The functionalized BN-containing luminogens have been explored for the detection of latent fingerprints (LFPs) on different substrates, including glass, aluminum foil, plastic, and ironware. This strategy provides great versatility in LFP imaging and good potential in elucidating the chemical information within LFPs, making the strategy valuable in forensic investigations.

The 5-Hydroxymethylcytosine (5hmC) Reader UHRF2 Is Required for Normal Levels of 5hmC in Mouse Adult Brain and Spatial Learning and Memory.

UHRF2 has been implicated as a novel regulator for both DNA methylation (5mC) and hydroxymethylation (5hmC), but its physiological function and role in DNA methylation/hydroxymethylation are unknown. Here we show that in mice, UHRF2 is more abundantly expressed in the brain and a few other tissues. Uhrf2 knock-out mice are viable and fertile and exhibit no gross defect. Although there is no significant change of DNA methylation, the Uhrf2 null mice exhibit a reduction of 5hmC in the brain, including the cortex and hippocampus. Furthermore, the Uhrf2 null mice exhibit a partial impairment in spatial memory acquisition and retention. Consistent with the phenotype, gene expression profiling uncovers a role for UHRF2 in regulating neuron-related gene expression. Finally, we provide evidence that UHRF2 binds 5hmC in cells but does not appear to affect the TET1 enzymatic activity. Together, our study supports UHRF2 as a bona fide 5hmC reader and further demonstrates a role for 5hmC in neuronal function.