Efficient characterization of multiple binding sites of small molecule imaging ligands on amyloid-beta, tau and alpha-synuclein.

PURPOSE: There is an unmet need for compounds to detect fibrillar forms of alpha-synuclein (αSyn) and 4-repeat tau, which are critical in many neurodegenerative diseases. Here, we aim to develop an efficient surface plasmon resonance (SPR)-based assay to facilitate the characterization of small molecules that can bind these fibrils. METHODS: SPR measurements were conducted to characterize the binding properties of fluorescent ligands/compounds toward recombinant amyloid-beta (Aß)42, K18-tau, full-length 2N4R-tau and αSyn fibrils. In silico modeling was performed to examine the binding pockets of ligands on αSyn fibrils. Immunofluorescence staining of postmortem brain tissue slices from Parkinson's disease patients and mouse models was performed with fluorescence ligands and specific antibodies. RESULTS: We optimized the protocol for the immobilization of Aß42, K18-tau, full-length 2N4R-tau and αSyn fibrils in a controlled aggregation state on SPR-sensor chips and for assessing their binding to ligands. The SPR results from the analysis of binding kinetics suggested the presence of at least two binding sites for all fibrils, including luminescent conjugated oligothiophenes, benzothiazole derivatives, nonfluorescent methylene blue and lansoprazole. In silico modeling studies for αSyn (6H6B) revealed four binding sites with a preference for one site on the surface. Immunofluorescence staining validated the detection of pS129-αSyn positivity in the brains of Parkinson's disease patients and αSyn preformed-fibril injected mice, 6E10-positive Aß in arcAß mice, and AT-8/AT-100-positivity in pR5 mice. CONCLUSION: SPR measurements of small molecules binding to Aß42, K18/full-length 2N4R-tau and αSyn fibrils suggested the existence of multiple binding sites. This approach may provide efficient characterization of compounds for neurodegenerative disease-relevant proteinopathies.

Role of TRPC6 in apoptosis of skeletal muscle ischemia/reperfusion injury.

BACKGROUND: Skeletal muscle ischaemia-reperfusion injury (IRI) is a prevalent condition encountered in clinical practice, characterised by muscular dystrophy. Owing to limited treatment options and poor prognosis, it can lead to movement impairments, tissue damage, and disability. This study aimed to determine and verify the influence of transient receptor potential canonical 6 (TRPC6) on skeletal muscle IRI, and to explore the role of TRPC6 in the occurrence of skeletal muscle IRI and the signal transduction pathways activated by TRPC6 to provide novel insights for the treatment and intervention of skeletal muscle IRI. METHODS: In vivo ischaemia/reperfusion (I/R) and in vitro hypoxia/reoxygenation (H/R) models were established, and data were comprehensively analysed at histopathological, cellular, and molecular levels, along with the evaluation of the exercise capacity in mice. RESULTS: By comparing TRPC6 knockout mice with wild-type mice, we found that TRPC6 knockout of TRPC6 could reduced skeletal muscle injury after I/R or H/R, of skeletal muscle, so as therebyto restoringe some exercise capacity inof mice. TRPC6 knockdown can reduced Ca2+ overload in cells, therebyo reducinge apoptosis. In additionAdditionally, we also found that TRPC6 functionsis not only a key ion channel involved in skeletal muscle I/R injury, but also can affects Ca2+ levels and then phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signalling pathway. by knocking downTherefore, knockdown of TRPC6, so as to alleviated the injury inducedcaused by skeletal muscle I/R or and H/R. CONCLUSIONS: These findingsdata indicate that the presence of TRPC6 exacerbatescan aggravate the injury of skeletal muscle injury after I/Rischemia/reperfusion, leading towhich not only causes Ca2+ overload and apoptosis., Additionally, it impairsbut also reduces the self- repair ability of cells by inhibiting the expression of the PI3K/Akt/mTOR signalling pathway. ETo exploringe the function and role of TRPC6 in skeletal muscle maycan presentprovide a novelew approachidea for the treatment of skeletal muscle ischemia/reperfusion injury.

Cell-type-specific effects of age and sex on human cortical neurons.

Altered transcriptional and epigenetic regulation of brain cell types may contribute to cognitive changes with advanced age. Using single-nucleus multi-omic DNA methylation and transcriptome sequencing (snmCT-seq) in frontal cortex from young adult and aged donors, we found widespread age- and sex-related variation in specific neuron types. The proportion of inhibitory SST- and VIP-expressing neurons was reduced in aged donors. Excitatory neurons had more profound age-related changes in their gene expression and DNA methylation than inhibitory cells. Hundreds of genes involved in synaptic activity, including EGR1, were less expressed in aged adults. Genes located in subtelomeric regions increased their expression with age and correlated with reduced telomere length. We further mapped cell-type-specific sex differences in gene expression and X-inactivation escape genes. Multi-omic single-nucleus epigenomes and transcriptomes provide new insight into the effects of age and sex on human neurons.

Identification and Application of CLE Peptides for Drought Resistance in Solanaceae Crops.

The CLE (CLAVATA3/Embryo Surrounding Region-related) family, a group of peptides with hormone-like features, plays a pivotal role in plant growth, development, and adaptation to stress. Through homology-based blast analysis of 32 Arabidopsis thaliana CLE peptide sequences, we have identified 5, 14, and 10 CLE family members in Nicotiana tabacum, Capsicum annuum, and Solanum melongena, respectively. Chemical synthesis and functional assays of the peptides led to the discovery that NtCLE3 substantially enhances the drought resistance of these three Solanaceae crops. Our transcriptome, RT-qPCR, and antioxidant enzyme activity data showed that NtCLE3 increased antioxidant capacity and ABA synthesis in tobacco. Moreover, the recombinant protein RPNtCLE3, composed of 6*NtCLE3, preserved the capacity to foster drought resilience and proved to be a promising drought resistance regulator, which presents a more favorable alternative for field applications compared to ABA which degrades rapidly under sunlight exposure. This research unveils the prospective utility of NtCLE3 in enhancing drought tolerance in Solanaceae crops and provides new ideas for the development of novel bioregulators aimed at mitigating drought stress.

Intelligent nanovesicle for remodeling tumor microenvironment and circulating tumor chemoimmunotherapy amplification.

Imperceptible examination and unideal treatment effect are still intractable difficulties for the clinical treatment of pancreatic ductal adenocarcinoma (PDAC). At present, despite 5-fluorouracil (5-FU), as a clinical first-line FOLFIRINOX chemo-drug, has achieved significant therapeutic effects. Nevertheless, these unavoidable factors such as low solubility, lack of biological specificity and easy to induce immunosuppressive surroundings formation, severely limit their treatment in PDAC. As an important source of energy for many tumor cells, tryptophan (Trp), is easily degraded to kynurenine (Kyn) by indolamine 2,3- dioxygenase 1 (IDO1), which activates the axis of Kyn-AHR to form special suppressive immune microenvironment that promotes tumor growth and metastasis. However, our research findings that 5-FU can induce effectively immunogenic cell death (ICD) to further treat tumor by activating immune systems, while the secretion of interferon-γ (IFN-γ) re-induce the Kyn-AHR axis activation, leading to poor treatment efficiency. Therefore, a metal matrix protease-2 (MMP-2) and endogenous GSH dual-responsive liposomal-based nanovesicle, co-loading with 5-FU (anti-cancer drug) and NLG919 (IDO1 inhibitor), was constructed (named as ENP919@5-FU). The multifunctional ENP919@5-FU can effectively reshape the tumor immunosuppression microenvironment to enhance the effect of chemoimmunotherapy, thereby effectively inhibiting cancer growth. Mechanistically, PDAC with high expression of MMP-2 will propel the as-prepared nanovesicle to dwell in tumor region via shedding PEG on the nanovesicle surface, effectively enhancing tumor uptake. Subsequently, the S-S bond containing nanovesicle was cut via high endogenous GSH, leading to the continued release of 5-FU and NLG919, thereby enabling circulating chemoimmunotherapy to effectively cause tumor ablation. Moreover, the combination of ENP919@5-FU and PD-L1 antibody (αPD-L1) showed a synergistic anti-tumor effect on the PDAC model with abdominal cavity metastasis. Collectively, ENP919@5-FU nanovesicle, as a PDAC treatment strategy, showed excellent antitumor efficacy by remodeling tumor microenvironment to circulate tumor chemoimmunotherapy amplification, which has promising potential in a precision medicine approach.

Identification of FTY720 and COH29 as novel topoisomerase I catalytic inhibitors by experimental and computational studies.

The development of novel topoisomerase I (TOP1) inhibitors is crucial for overcoming the drawbacks and limitations of current TOP1 poisons. Here, we identified two potential TOP1 inhibitors, namely, FTY720 (a sphingosine 1-phosphate antagonist) and COH29 (a ribonucleotide reductase inhibitor), through experimental screening of known active compounds. Biological experiments verified that FTY720 and COH29 were nonintercalative TOP1 catalytic inhibitors that did not induce the formation of DNA-TOP1 covalent complexes. Molecular docking revealed that FTY720 and COH29 interacted favorably with TOP1. Molecular dynamics simulations revealed that FTY720 and COH29 could affect the catalytic domain of TOP1, thus resulting in altered DNA-binding cavity size. The alanine scanning and interaction entropy identified Arg536 as a hotspot residue. In addition, the bioinformatics analysis predicted that FTY720 and COH29 could be effective in treating malignant breast tumors. Biological experiments verified their antitumor activities using MCF-7 breast cancer cells. Their combinatory effects with TOP1 poisons were also investigated. Further, FTY720 and COH29 were found to cause less DNA damage compared with TOP1 poisons. The findings provide reliable lead compounds for the development of novel TOP1 catalytic inhibitors and offer new insights into the potential clinical applications of FTY720 and COH29 in targeting TOP1.

Low-Symmetry 2D t-InTe for Polarization-Sensitive UV-Vis-NIR Photodetection.

Polarization-sensitive photodetection grounded on low-symmetry 2D materials has immense potential in improving detection accuracy, realizing intelligent detection, and enabling multidimensional visual perception, which has promising application prospects in bio-identification, optical communications, near-infrared imaging, radar, military, and security. However, the majority of the reported polarized photodetection are limited by UV-vis response range and low anisotropic photoresponsivity factor, limiting the achievement of high-performance anisotropic photodetection. Herein, 2D t-InTe crystal is introduced into anisotropic systems and developed to realize broadband-response and high-anisotropy-ratio polarized photodetection. Stemming from its narrow band gap and intrinsic low-symmetry lattice characteristic, 2D t-InTe-based photodetector exhibits a UV-vis-NIR broadband photoresponse and significant photoresponsivity anisotropy behavior, with an exceptional in-plane anisotropic factor of 1.81@808 nm laser, surpassing the performance of most reported 2D counterparts. This work expounds the anisotropic structure-activity relationship of 2D t-InTe crystal, and identifies 2D t-InTe as a prospective candidate for high-performance polarization-sensitive optoelectronics, laying the foundation for future multifunctional device applications.

Primary leiomyosarcoma of the thyroid gland: A rare case report and literature review.

INTRODUCTION: Primary thyroid leiomyosarcoma is an extremely rare soft tissue sarcoma, characterized by high malignancy and poor prognosis. Currently, only 13 cases of primary thyroid leiomyosarcoma have been described in the medical literature (limited to English). CASE PRESENTATION: A 76-year-old female presented with a giant neck mass. Physical examination revealed a large, firm mass in the left thyroid gland. No symptoms such as hoarseness or dysphagia were noted at the time of presentation. The patient underwent unilateral thyroidectomy and cervical lymph node dissection. CLINICAL DISCUSSION: Pathologic findings revealed a low-grade sarcoma with spindle-shaped tumor cells in an interwoven, sheet-like distribution. Immunohistochemistry showed positivity for desmin, SMMHC, STAT6, CK19, and Galectin3, but negativity for S-100, MyoD1, CD34, CK (AE1/AE3), CD117, and CD56. The findings were consistent with thyroid leiomyosarcoma. CONCLUSION: The treatment of primary thyroid LMS presents challenges due to its atypical symptoms and high malignance, highlighting the imperative for further exploration of therapeutic strategies to improve the outcomes.

Hericenone C attenuates the second phase of formalin-induced nociceptive behavior by suppressing the accumulation of CD11c-positive cells in the paw epidermis via phosphorylated P65.

Hericenone C is one of the most abundant secondary metabolites derived from Hericium erinaceus, under investigation for medicinal properties. Here, we report that Hericenone C inhibits the second phase of formalin-induced nociceptive behavior in mice. As the second phase is involved in inflammation, in a mechanistic analysis on cultured cells targeting NF-κB response element (NRE): luciferase (Luc)-expressing cells, lipopolysaccharide (LPS)-induced NRE::Luc luciferase activity was found to be significantly inhibited by Hericenone C. Phosphorylation of p65, which is involved in the inflammatory responses of the NF-κB signaling pathway, was also induced by LPS and significantly reduced by Hericenone C. Additionally, in mice, the number of CD11c-positive cells increased in the paw during the peak of the second phase of the formalin test, which decreased upon Hericenone C intake. Our findings confirm the possibility of Hericenone C as a novel therapeutic target for pain-associated inflammation.

Exploring the Interactions between two Ligands, UCB-J and UCB-F, and Synaptic Vesicle Glycoprotein 2 Isoforms.

In silico modeling was applied to study the efficiency of two ligands, namely, UCB-J and UCB-F, to bind to isoforms of the synaptic vesicle glycoprotein 2 (SV2) that are involved in the regulation of synaptic function in the nerve terminals, with the ultimate goal to understand the selectivity of the interaction between UCB-J and UCB-F to different isoforms of SV2. Docking and large-scale molecular dynamics simulations were carried out to unravel various binding patterns, types of interactions, and binding free energies, covering hydrogen bonding and nonspecific hydrophobic interactions, water bridge, π-π, and cation-π interactions. The overall preference for bonding types of UCB-J and UCB-F with particular residues in the protein pockets can be disclosed in detail. A unique interaction fingerprint, namely, hydrogen bonding with additional cation-π interaction with the pyridine moiety of UCB-J, could be established as an explanation for its high selectivity over the SV2 isoform A (SV2A). Other molecular details, primarily referring to the presence of π-π interactions and hydrogen bonding, could also be analyzed as sources of selectivity of the UCB-F tracer for the three isoforms. The simulations provide atomic details to support future development of new selective tracers targeting synaptic vesicle glycoproteins and their associated diseases.

Dynamic effective connectivity in the cerebellar dorsal dentate nucleus and the cerebrum, cognitive impairment, and clinical correlates in patients with schizophrenia.

BACKGROUND: Schizophrenia (SZ) is characterized by disconnected cerebral networks. Recent studies have shown that functional connectivity between the cerebellar dorsal dentate nucleus (dDN) and cerebrum is correlated with psychotic symptoms, and processing speed in SZ patients. Dynamic effective connectivity (dEC) is a reliable indicator of brain functional status. However, the dEC between the dDN and cerebrum in patients with SZ remains largely unknown. METHODS: Resting-state functional MRI data, symptom severity, and cognitive performance were collected from 74 SZ patients and 53 healthy controls (HC). Granger causality analysis and sliding time window methods were used to calculate dDN-based dEC maps for all subjects, and k-means clustering was performed to obtain several dEC states. Finally, between-group differences in dynamic effective connectivity variability (dECV) and clinical correlations were obtained using two-sample t-tests and correlation analysis. RESULTS: We detected four dEC states from the cerebrum to the right dDN (IN states) and three dEC states from the right dDN to the cerebrum (OUT states), with SZ group having fewer transitions in the OUT states. SZ group had increased dECV from the right dDN to the right middle frontal gyrus (MFG) and left lingual gyrus (LG). Correlations were found between the dECV from the right dDN to the right MFG and symptom severity and between the dECV from the right dDN to the left LG and working memory performance. CONCLUSIONS: This study reveals a dynamic causal relationship between cerebellar dDN and the cerebrum in SZ and provides new evidence for the involvement of cerebellar neural circuits in neurocognitive functions in SZ.

Functional screening of the Arabidopsis 2C protein phosphatases family identifies PP2C15 as a negative regulator of plant immunity by targeting BRI1-associated receptor kinase 1.

Genetic engineering using negative regulators of plant immunity has the potential to provide a huge impetus in agricultural biotechnology to achieve a higher degree of disease resistance without reducing yield. Type 2C protein phosphatases (PP2Cs) represent the largest group of protein phosphatases in plants, with a high potential for negative regulatory functions by blocking the transmission of defence signals through dephosphorylation. Here, we established a PP2C functional protoplast screen using pFRK1::luciferase as a reporter and found that 14 of 56 PP2Cs significantly inhibited the immune response induced by flg22. To verify the reliability of the system, a previously reported MAPK3/4/6-interacting protein phosphatase, PP2C5, was used; it was confirmed to be a negative regulator of PAMP-triggered immunity (PTI). We further identified PP2C15 as an interacting partner of BRI1-associated receptor kinase 1 (BAK1), which is the most well-known co-receptor of plasma membrane-localized pattern recognition receptors (PRRs), and a central component of PTI. PP2C15 dephosphorylates BAK1 and negatively regulates BAK1-mediated PTI responses such as MAPK3/4/6 activation, defence gene expression, reactive oxygen species bursts, stomatal immunity, callose deposition, and pathogen resistance. Although plant growth and 1000-seed weight of pp2c15 mutants were reduced compared to those of wild-type plants, pp2c5 mutants did not show any adverse effects. Thus, our findings strengthen the understanding of the mechanism by which PP2C family members negatively regulate plant immunity at multiple levels and indicate a possible approach to enhance plant resistance by eliminating specific PP2Cs without affecting plant growth and yield.

Preparation and Properties of Low-Dielectric Polyimide Films Containing Tert-Butyl.

The design of high-performance polyimide (PI) films and understanding the relationship of the structure-dielectric property are of great significance in the field of the microelectronics industry, but are challenging. Herein, we describe the first work to construct a series of novel tert-butyl PI films (denoted as PI-1, PI-2, PI-3, and PI-4) based on a low-temperature polymerization strategy, which employed tetracarboxylic dianhydride (pyromellitic anhydride, 3,3',4,4'-biphenyl tetracarboxylic anhydride, 4,4'-diphenyl ether dianhydride, and 3,3',4,4'-benzophenone tetracarboxylic anhydride) and 4,4'-diamino-3,5-ditert butyl biphenyl ether as monomers. The results indicate that introducing tert-butyl branches in the main chain of PIs can enhance the free volume of the molecular chain and reduce the interaction between molecular chains of PI, resulting in a low dielectric constant. Particularly, the optimized PI-4 exhibits an excellent comprehensive performance with a high (5) wt% loss temperature (454 °C), tensile strength (117.40 MPa), and maximum hydrophobic angle (80.16°), and a low dielectric constant (2.90), which outperforms most of the results reported to date.

Rapid low-temperature densification of Ag2Se bulk material: mass transfer through the dissociative adsorption reaction of Ag protrusions and Se saturated vapor.

In materials science, the impact of density on a material's capabilities is profound. Conventional sintering requires high temperatures and is energy-demanding, propelling the pursuit of less intensive, low-temperature densification methods. Electric field-assisted sintering has recently gained attention for its simplicity and effectiveness, offering a new frontier in low-temperature densification. In this study, dense bulk materials were produced by subjecting monophasic Ag2Se powders to electric field-assisted sintering, where a direct current with an average value of 4 A was applied, achieving a peak temperature of 344 K. The novel low-temperature densification mechanism unfolds thus: nanoscale silver protrusions, stimulated by electrical current, engage in a dissociative adsorption reaction with the ambient saturated selenium vapor. This process swiftly engenders the formation of fresh silver selenide (Ag2Se) compounds, initiating nucleation and subsequent growth. Consecutively, these compounds seamlessly occupy and expand, perpetually bridging the interstices amidst the powders. In a scant 8 s, the density swiftly surpassed 99%, yielding a bulk material that exhibited aZTvalue of 1.07 at 390 K. This investigation not only attains an unparalleled density at low temperatures but also charts a pioneering course for material densification in such conditions.

Dual-Cation CuAgSe-Based Material: Rapid Mass Transfer in Synthesis and High Thermoelectric Performance Realization.

Understanding mass transfer mechanisms is vital for developing new material synthesis and densification technologies. Ion transport, serving both mass and charge transfer, is essential for the rapid preparation of high-performance fast ionic conductor thermoelectric materials like Zn4Sb3 and Cu2Q (Q = S, Se). In the case of dual-cation fast ion conductor materials like CuAgSe, exploring the relationship between cation transport becomes pertinent. In this study, copper (Cu) and selenium (Se) undergo a reaction in the presence of an electric field (∼15 A), resulting in the formation of the CuSe compound. Subsequent to this initial reaction, a subsequent thermal environment facilitates the interaction among Cu, CuSe, and Ag2Se, culminating in the rapid formation and densification of CuAgSe (with a relative density exceeding 99%) in just 30 s. Evidently, the diffusion of copper ions substantiates a pivotal role in facilitating mass transfer. As a result, CuAg1+xSe samples with different silver contents (x = 0.01, 0.02, 0.03, 0.04 and 0.05) can effectively inhibit cation vacancy, and introduce highly ordered Ag nanotwins to enhance the electrical transport performance. For CuAg1.04Se, a peak ZT value of 1.0 can be achieved at 673 K, which is comparable to the literatures. This work will guide the future electric field-assisted rapid mass transfer of materials.

The Failure Mechanism of Micro Thermoelectric Devices under the Action of the Temperature Field.

The micro thermoelectric device (m-TED) boasts features such as adjustable volume, straightforward structure, and precise, rapid temperature control, positioning it as the only current solution for managing the temperature of microelectronic systems. It is extensively utilized in 5G optical modules, laser lidars, and infrared detection. Nevertheless, as the size of the m-TED diminishes, the growing proportion of interface damages the device's operational reliability, constraining the advancement of the m-TED. In this study, we used commercially available bismuth telluride materials to construct the m-TED. The device's reliability was tested under various temperatures: -40, 85, 125, and 150 °C. By deconstructing and analyzing the devices that failed during the tests, we discovered that the primary cause of device failure was the degradation of the solder layer. Moreover, we demonstrated that encapsulating the device with polydimethylsiloxane (PDMS) could effectively delay the deterioration of its performance. This study sparks new insights into the service reliability of m-TEDs and paves the way for further optimizing device interface design and enhancing the device manufacturing process.

Dependence of Interlayer or Sulfur Host on Hollow Framework of Lithium-Sulfur Battery.

Lithium-sulfur batteries are recognized as the next generation of high-specific energy secondary batteries owing to their satisfactory theoretical specific capacity and energy density. However, their commercial application is greatly limited by a series of problems, including disordered migration behavior, sluggish redox kinetics, and the serious shuttle effect of lithium polysulfides. One of the most efficient approaches to physically limit the shuttle effect is the rational design of a hollow framework as sulfur host. However, the influence of the hollow structure on the interlayers has not been clearly reported. In this study, the Mo2 C/C catalysts with hollow(H-Mo2 C/C) and solid(S-Mo2 C/C) frameworks are rationally designed to explore the dependence of the hollow structure on the interlayer or sulfur host. In contrast to the physical limitations of the hollow framework as host, the hollow structure of the interlayer inhibited lithium-ion diffusion, resulting in poor electrochemical properties at high current densities. Based on the superiority of the various frameworks, the H-Mo2 C/C@S | S-Mo2 C/C@PP | Li cells are assembled and displayed excellent electrochemical performance. This work re-examines the design requirements and principles of catalyst frameworks in different battery units.

Association between degree centrality and neurocognitive impairments in patients with Schizophrenia: A Longitudinal rs-fMRI Study.

BACKGROUND: Evidence indicates that patients with schizophrenia (SZ) experience significant changes in their functional connectivity during antipsychotic treatment. Despite previous reports of changes in brain network degree centrality (DC) in patients with schizophrenia, the relationship between brain DC changes and neurocognitive improvement in patients with SZ after antipsychotic treatment remains elusive. METHODS: A total of 74 patients with acute episodes of chronic SZ and 53 age- and sex-matched healthy controls were recruited. The Positive and Negative Syndrome Scale (PANSS), Symbol Digit Modalities Test, digital span test (DST), and verbal fluency test were used to evaluate the clinical symptoms and cognitive performance of the patients with SZ. Patients with SZ were treated with antipsychotics for six weeks starting at baseline and underwent MRI and clinical interviews at baseline and after six weeks, respectively. We then divided the patients with SZ into responding (RS) and non-responding (NRS) groups based on the PANSS scores (reduction rate of PANSS ≥50%). DC was calculated and analyzed to determine its correlation with clinical symptoms and cognitive performance. RESULTS: After antipsychotic treatment, the patients with SZ showed significant improvements in clinical symptoms, semantic fluency performance. Correlation analysis revealed that the degree of DC increase in the left anterior inferior parietal lobe (aIPL) after treatment was negatively correlated with changes in the excitement score (r = -0.256, p = 0.048, adjusted p = 0.080), but this correlation failed the multiple test correction. Patients with SZ showed a significant negative correlation between DC values in the left aIPL and DST scores after treatment, which was not observed at the baseline (r = -0.359, p = 0.005, adjusted p = 0.047). In addition, we did not find a significant difference in DC between the RS and NRS groups, neither at baseline nor after treatment. CONCLUSIONS: The results suggested that DC changes in patients with SZ after antipsychotic treatment are correlated with neurocognitive performance. Our findings provide new insights into the neuropathological mechanisms underlying antipsychotic treatment of SZ.

Hematopoietic Prostaglandin D Synthase Is Increased in Mast Cells and Pericytes in Autopsy Myocardial Specimens from Patients with Duchenne Muscular Dystrophy.

The leading cause of death for patients with Duchenne muscular dystrophy (DMD), a progressive muscle disease, is heart failure. Prostaglandin (PG) D2, a physiologically active fatty acid, is synthesized from the precursor PGH2 by hematopoietic prostaglandin D synthase (HPGDS). Using a DMD animal model (mdx mice), we previously found that HPGDS expression is increased not only in injured muscle but also in the heart. Moreover, HPGDS inhibitors can slow the progression of muscle injury and cardiomyopathy. However, the location of HPGDS in the heart is still unknown. Thus, this study investigated HPGDS expression in autopsy myocardial samples from DMD patients. We confirmed the presence of fibrosis, a characteristic phenotype of DMD, in the autopsy myocardial sections. Additionally, HPGDS was expressed in mast cells, pericytes, and myeloid cells of the myocardial specimens but not in the myocardium. Compared with the non-DMD group, the DMD group showed increased HPGDS expression in mast cells and pericytes. Our findings confirm the possibility of using HPGDS inhibitor therapy to suppress PGD2 production to treat skeletal muscle disorders and cardiomyopathy. It thus provides significant insights for developing therapeutic drugs for DMD.