Intranasal Delivery of Curcumin Nanoparticles Improves Neuroinflammation and Neurological Deficits in Mice with Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) represents one of the most severe subtypes of stroke. Due to the complexity of the brain injury mechanisms following ICH, there are currently no effective treatments to significantly improve patient functional outcomes. Curcumin, as a potential therapeutic agent for ICH, is limited by its poor water solubility and oral bioavailability. In this study, mPEG-PCL is used to encapsulate curcumin, forming curcumin nanoparticles, and utilized the intranasal administration route to directly deliver curcumin nanoparticles from the nasal cavity to the brain. By inhibiting pro-inflammatory neuroinflammation of microglia following ICH in mice, reprogramming pro-inflammatory microglia toward an anti-inflammatory function, and consequently reducing neuronal inflammatory death and hematoma volume, this approach improved blood-brain barrier damage in ICH mice and promoted the recovery of neurological function post-stroke. This study offers a promising therapeutic strategy for ICH to mediate neuroinflammatory microenvironments.

Illegal synthetic dyes in spices: a Singapore case study.

Some synthetic dyes are fraudulently added into spices to appeal visually to consumers. Food regulations in several countries, including the United States, Australia, Japan and the European Union, strictly prohibit the use of unauthorised synthetic dyes in food. Nevertheless, illegal practices persist, where spices contaminated with potentially carcinogenic dyes have been documented, posing potential health risks to consumers. In the present study, 14 synthetic dyes were investigated through liquid chromatography/tandem mass spectrometry in 252 commercially available spices in the Singapore market. In 18 out of these (7.1%) at least 1 illegal dye was detected at concentrations ranging from 0.010 to 114 mg/kg. Besides potential health risks, presence of these adulterants also reflects the economic motivations behind their fraudulent use. Findings in the present study further emphasise the need for increased public awareness, stricter enforcement, and continuous monitoring of illegal synthetic dyes in spices to ensure Singapore's food safety.

Determination of ethoxyquin by ultra-high performance liquid chromatography with tandem mass spectrometry and a Singapore survey of ethoxyquin residues in eggs, egg products and poultry.

In this study, an advanced ultra-high performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was developed for quantifying ethoxyquin (EQ). The approach employed a distinctive antioxidant added extraction step designed to prevent ethoxyquin decomposition and maintain analytical precision. This method effectively determines residue levels of EQ in eggs, processed egg products, poultry muscle, salmon, and liquid milk. The method was shown to have a limit of quantitation (LOQ) for eggs, milk, salmon, and chicken muscle of 1.5 µg/kg, 1.9 µg/kg, 2.1 µg/kg, and 1.2 µg/kg, respectively. The recoveries of EQ ranged from 79.2% to 107.6%, with a relative standard deviation (RSD) below 8.4%. A surveillance study for the presence of EQ in different types of eggs and poultry muscle available in Singapore was conducted and a total of 140 samples were tested. EQ residues in all samples were found to be below the U.S. Food and Drug Administration (FDA) MRLs of 500 µg/kg. Some samples of salted and preserved eggs from China were detected with higher concentration of EQ.

Grifola frondosa polysaccharides: A review on structure/activity, biosynthesis and engineering strategies.

Polysaccharides are the main polymers in edible fungi Grifola frondosa, playing a crucial role in the physiology and representing the healthy benefits for humans. Recent efforts have well elucidated the fine structures and biological functions of G. frondosa polysaccharides. The recently-rapid developments and increasing availability in fungal genomes also accelerated the better understanding of key genes and pathways involved in biosynthesis of G. frondosa polysaccharides. Herein, we provide a brief overview of G. frondosa polysaccharides and their activities, and comprehensively outline the complex process, genes and proteins corresponding to G. frondosa polysaccharide biosynthesis. The regulation strategies including strain improvement, process optimization and genetic engineering were also summarized for maximum production of G. frondosa polysaccharides. Some remaining unanswered questions in describing the fine synthesis machinery were also pointed out to open up new avenues for answering the structure-activity relationship and improving polysaccharide biosynthesis in G. frondosa. The review hopefully presents a reasonable full picture of activities, biosynthesis, and production regulation of polysaccharide in G. frondosa.

Recent insights into glucans biosynthesis and engineering strategies in edible fungi.

Fungal α/ß-glucans have significant importance in cellular functions including cell wall structure, host-pathogen interactions and energy storage, and wide application in high-profile fields, including food, nutrition, and pharmaceuticals. Fungal species and their growth/developmental stages result in a diversity of glucan contents, structures and bioactivities. Substantial progresses have been made to elucidate the fine structures and functions, and reveal the potential molecular synthesis pathway of fungal α/ß-glucans. Herein, we review the current knowledge about the biosynthetic machineries, including: precursor UDP-glucose synthesis, initiation, elongation/termination and remodeling of α/ß-glucan chains, and molecular regulation to maximally produce glucans in edible fungi. This review would provide future perspectives to biosynthesize the targeted glucans and reveal the catalytic mechanism of enzymes associated with glucan synthesis, including: UDP-glucose pyrophosphate phosphorylases (UGP), glucan synthases, and glucanosyltransferases in edible fungi.

Biochemical and structural characterization of a glucan synthase GFGLS2 from edible fungus Grifola frondosa to synthesize ß-1, 3-glucan.

BACKGROUND: Grifola frondosa is a Basidiomycete fungus belonging to the family of Grifolaceae and the order of Polyporales. ß-Glucans are the main polymers in G. frondosa, playing a crucial role in the physiology and representing the healthy benefits for humans. The membrane-integrated ß-1, 3-glucan synthase (GLS) is responsible for glucan synthesis, cell wall assembly, differentiation and growth of the edible fungi. However, the structural/catalytic characteristics and mechanisms of ß-1, 3-glucan synthases in G. frondosa are still unknown due to their extremely complex structures with multi-transmembranes and large molecular masses. RESULTS: Herein, a ß-1, 3-glucan synthase (GFGLS2) was purified and identified from the cultured mycelia with a specific activity of 60.01 pmol min-1 µg-1 for the first time. The GFGLS2 showed a strict specificity to UDP-glucose with a Vmax value of 1.29 ± 0.04 µM min-1 at pH 7.0 and synthesized ß-1, 3-glucan with a maximum degree of polymerization (DP) of 62. Sequence Similarity Network (SSN) analysis revealed that GFGLS2 has a close relationship with others in Ganoderma sinense, Trametes coccinea, Polyporus brumalis, and Trametes pubescens. With the assistance of 3D structure modelling by AlphaFold 2, molecular docking and molecular dynamics simulations, the central hydrophilic domain (Class III) in GFGLS2 was the main active sites through binding the substrate UDP-glucose to 11 amino acid residues via hydrogen bonds, π-stacking and salt bridges. CONCLUSIONS: The biochemical, 3D structural characterization and potential catalytic mechanism of a membrane-bound ß-1, 3-glucan synthase GFGLS2 from cultured mycelia of G. frondosa were well investigated and would provide a reasonable full picture of ß-1, 3-glucan synthesis in fungi.

Case Report: Successful Use of BRAF/MEK Inhibitors in Aggressive BRAF-mutant Craniopharyngioma.

BACKGROUND: Although a benign intracranial tumor, craniopharyngioma treatment has always been considered a challenging clinical problem. Recently, BRAF V600E mutation in the pathogenesis of papillary craniopharyngioma (PCP) has been further revealed. Thus, BRAF inhibitors (BRAFi) serve as an applicable treatment for patients with PCP. METHODS: Two patients with recurrent PCP were treated with combined BRAFi dabrafenib (150 mg, orally twice daily) and MEK inhibitors (MEKi) trametinib (2 mg, orally twice daily). A follow-up exceeding 2 years was conducted. We meticulously scrutinized the treatment's safety and efficacy profiles by delving into existing literature. RESULTS: One patient harboring a solid tumor achieved a complete tumor response devoid of any adverse events and encountered no recurrence over 2 years subsequent to discontinuation. Moreover, within a mere month of commencing targeted therapy, the tumor demonstrated observable shrinkage. This finding substantiates the considerable potential inherent in targeted therapy for PCP cases marked by the somatic BRAF V600E mutation. CONCLUSIONS: Under specific conditions, individuals diagnosed with PCP can attain a complete tumor response following combined treatment with BRAFi/MEKi.

Single-cell RNA sequencing highlights intratumor heterogeneity and intercellular network featured in adamantinomatous craniopharyngioma.

Despite improvements in microscopically neurosurgical techniques made in recent years, the prognosis of adamantinomatous craniopharyngioma (ACP) is still unsatisfactory. Little is known about cellular atlas and biological features of ACP. Here, we carried out integrative analysis of 44,038 single-cell transcriptome profiles to characterize the landscape of intratumoral heterogeneity and tumor microenvironment (TME) in ACP. Four major neoplastic cell states with distinctive expression signatures were defined, which further revealed the histopathological features and elucidated unknown cellular atlas of ACP. Pseudotime analyses suggested potential evolutionary trajectories between specific neoplastic cell states. Notably, a distinct oligodendrocyte lineage was identified in ACP, which was associated with immunological infiltration and neural damage. In addition, we described a tumor-centric regulatory network based on intercellular communication in TME. Together, our findings represent a unique resource for deciphering tumor heterogeneity of ACP, which will improve clinical diagnosis and treatment strategies.

MiR-144-5p/CCL12 Signaling Axis Modulates Ischemic Preconditioning-Mediated Cardio-protection by Reducing Cell Viability, Enhancing Cell Apoptosis, Fibrosis, and Pyroptosis.

Ischemic postconditioning (IPost) represents short periods of nonlethal ischemia-reperfusion performed at the onset of reperfusion. Studies have shown that IPost involves various biological processes such as cell proliferation, apoptosis, and pyroptosis and can activate complex signaling pathways. CCL12 is a critical mediator in the inflammatory process after tissue injury. In the present study, we examined the potential actions of CCL12-mediated signaling pathways in cardioprotection after IPost using a cardiomyocyte model. By applying the bioinformatics analysis, we found that CCL12 was upregulated in the rat heart tissues after I/R injury, and the expression level of CCL12 was restored in rats with IPost. The in vitro studies showed that CCL12 and CCR2 expression levels were upregulated in the hypoxia/reoxygenation (H/R)-induced H9C2 cells, which was attenuated in the H/R + hypoxia post-conditioning (PostC) group. The functional assays showed that H/R treatment reduced cell viability, increased cell apoptosis, and promoted fibrosis and pyroptosis of H9C2 cells, which was attenuated in the H/R + PostC group. Overexpression of CCL12 impaired the protective action of hypoxia post-conditioning in the H9C2 cells. Further mechanistic studies showed that miR-144-5p could directly target the 3' untranslated region of CCL12. Overexpression of miR-144-5p markedly repressed the expression levels of CCL12 and CCR2 in H9C2 cells, while miR-144-5p inhibition had the opposite effects. Furthermore, the inhibition of miR-144-5p reduced the cell viability, increased cell apoptosis, and enhanced fibrosis and pyroptosis of H9C2 cells after H/R or H/R + PostC treatment. In conclusion, CCL12 was downregulated in cardiomyocytes following ischemic postconditioning, and CCL12 overexpression impaired the cardioprotective actions of ischemic postconditioning by reducing cell viability, enhancing cell apoptosis, fibrosis, and pyroptosis. Further mechanistic evidence revealed that CCL12 was a direct target of miR-144-5p, and miR-144-5p/CCL12/CCR2 signaling may represent a critical pathway in mediating the cardioprotective effects of ischemic postconditioning.

Epileptic convulsions probably induced by desloratadine: a case report.

Desloratadine, a second generation H1-antihistamine, is generally considered to be safe. We found only one article reporting four children with a family or disease history of epilepsy who developed the condition after desloratadine treatment, with all four patients recovering well. Here we describe a healthy boy who developed left-arm convulsions on day 68 after taking desloratadine, at which point the desloratadine treatment was immediately stopped. Investigations were completed on day 83 and the patient was diagnosed with epilepsy. He was prescribed sodium valproate combined with oxcarbazepine, topiramate, lamotrigine and clonazepam for 15 months, which did not control the convulsions. During the following 3 months the patient received sodium valproate combined with lacosamide, and on day 615 the seizures stopped and no further convulsions occurred. At the follow-up, his father reported that the boy's memory was not as good as it had been previously. The convulsions continued after the withdrawal of desloratadine; therefore, the pathological mechanism of convulsion and the treatment plan need further research.

Expression and clinical significance of VISTA, B7-H3, and PD-L1 in glioma.

Immune checkpoint (IC) therapy has led to a breakthrough in cancer treatment. However, the interaction of ICs is controversial in glioma. We detected features of ICs using transcriptome data and a multicolor immunofluorescence assay. We discovered that B7-H3 increased with grade and age and predicted worse overall survival (OS) at the transcriptional and proteomic levels. VISTA and PD-L1 were associated with OS and grade at the RNA level. At the protein level, VISTA was primarily expressed in tumor cells and TAMs. B7-H3 and VISTA were positively correlated with PD-L1. There was a strong correlation between PD-L1 and CD3 and between VISTA and IBA-1. PD-L1 was coexpressed with T cells. VISTA was coexpressed with TAMs. In T cells, we found a strong correlation in ICs, which worsened in TAMs and tumor cells. In conclusion, B7-H3 is a vital prognostic target for immunotherapy. We provided a potential mechanism for the immunosuppressive microenvironment in glioma.

Enhanced anti-glioma efficacy of doxorubicin with BRD4 PROTAC degrader using targeted nanoparticles.

Current treatment of glioma is hampered due to the physical blood-brain barrier (BBB) and the resistance to traditional chemotherapeutic agents. Herein, we proposed a combined treatment strategy based on Cyclo (Arg-Gly-Asp-d-Phe-Lys) (cRGDfk) peptides-modified nanoparticle named cRGD-P in a self-assembly method for the co-delivery of doxorubicin (DOX) and BRD4 PROTAC degrader ARV-825 (ARV). Molecular dynamics simulations showed that cRGD-P could change its conformation to provide interaction sites for perfectly co-loading DOX and ARV. The cRGD-P/ARV-DOX exhibited an average size of 39.95 â€‹nm and a zeta potential of -0.25 â€‹mV. Increased expression of BRD4 in glioma cells was observed after being stimulated by cRGD-P/DOX, confirming one of the possible mechanisms of DOX resistance and the synergistic tumor inhibition effect of BRD4 degrading ARV combined with DOX. In the study, the combination of DOX and ARV in the cRGD-P nanoparticle system exhibited synergistic suppression of tumor growth in glioma cells on account of cell cycle arrest in the G2/M phase and the activation of tumor cells apoptosis-related pathways including triggering caspase cascade and downregulating Bcl-2 as well as upregulating Bax. The cRGD-P/ARV-DOX system could effectively suppress the heterotopic and orthotopic growth of glioma by increasing tumor apoptosis, inhibiting tumor proliferation, and decreasing tumor angiogenesis in vivo. Therefore, the cRGD-modified nanoparticle to co-deliver DOX and ARV provides a potential platform for exploiting a more effective and safer combination therapy for glioma.

Benign optic nerve gliomas in an adult: A case report.

RATIONALE: Benign optic nerve gliomas were rarely found in adults, and total resection of these lesions seems impossible. We aimed to share a rare clinical case with an unusual and instructive treatment process. PATIENT CONCERNS: A 52-year-old woman complained of a 4-month history of visual disturbance. Automated perimetry revealed visual field defect in her both eyes. DIAGNOSIS: This patient was diagnosed with optic nerve glioma. We found its pathological features consistent with the pilocytic astrocytomas (WHO grade I). INTERVENTIONS: A total resection of the tumor was smoothly performed. OUTCOMES: Repeat MRI 3 months after the surgery demonstrated no recurrence of the lesion. Two years of postoperative telephone follow-up showed a stable status of improved vision. LESSONS: We reported this interesting case to show a rare kind of condition regarding optic nerve gliomas in adults, which might help neurosurgeons like us to diagnose and treat these "invisible" tumors.

Lactate dehydrogenase predicting mortality in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Lactate dehydrogenase (LDH) has been reported to be associated with outcomes after surgery in patients with aneurysmal subarachnoid hemorrhage (aSAH), but it is unclear if this is independent from other biomarkers and across all aSAH treatments. This study aims to assess whether LDH is an independent predictor of mortality in patients with aSAH and test whether the inclusion of LDH in a well-established prediction model can improve discrimination and reclassification. METHODS: This was a retrospective observational study at a tertiary academic medical center. This study measured baseline LDH levels taken at admission and longitudinal LDH levels (up to a month postadmission) to assess median, max, and trajectory LDH levels. The primary outcome was mortality at 90 days. Multivariable regression analyses were used to evaluate associations between LDH and outcomes. The full original Subarachnoid Hemorrhage International Trialists' (SAHIT) model was used as the reference model. RESULTS: In total, 3524 patients with aSAH were included. LDH at admission was independently associated with mortality at 90 days (quartile 4 vs. 1: odds ratio 1.60; 95% CI 1.08-2.37) and mortality at the longest follow-up (quartile 4 vs. 1: hazard ratio1.72; 95% CI 1.34-2.20). Compared with the SAHIT model, the addition of three LDH (admission, max, and median) levels to the SAHIT model significantly improved the area under the curve and categorical net reclassification improvement for prediction mortality. INTERPRETATION: In patients with aSAH, LDH level is an independent predictor of all-cause mortality. The incorporation of LDH into a well-established prediction model improved the ability to predict the risk of death in patients with aSAH.

Functional Characterization and Structural Basis of the ß-1,3-Glucan Synthase CMGLS from Mushroom Cordyceps militaris.

ß-1,3-Glucan synthases play key roles in glucan synthesis, cell wall assembly, and growth of fungi. However, their multi-transmembrane domains (over 14 TMHs) and large molecular masses (over 100 kDa) significantly hamper understanding of their catalytic characteristics and mechanisms. In the present study, the 5841-bp gene CMGLS encoding the 221.7 kDa membrane-bound ß-1,3-glucan synthase CMGLS in Cordyceps militaris was cloned, identified, and structurally analyzed. CMGLS was partially purified with a specific activity of 87.72 pmol/min/µg, a purification fold of 121, and a yield of 10.16% using a product-entrapment purification method. CMGLS showed a strict specificity to UDP-glucose with a Km value of 84.28 µM at pH 7.0 and synthesized ß-1,3-glucan with a maximum degree of polymerization (DP) of 70. With the assistance of AlphaFold and molecular docking, the 3D structure of CMGLS and its binding features with substrate UDP-glucose were proposed for the first time to our knowledge. UDP-glucose potentially bound to at least 11 residues via hydrogen bonds, π-stacking ,and salt bridges, and Arg 1436 was predicted as a key residue directly interacting with the moieties of glucose, phosphate, and the ribose ring on UDP-glucose. These findings would open an avenue to recognize and understand the glucan synthesis process and catalytic mechanism of ß-1,3-glucan synthases in mushrooms.

[Advances in Intraoperative Neurophysiological Monitoring Techniques in Transnasal Endoscopic Skull Base Surgery].

Transnasal endoscopic skull base surgery has been increasing in volume in recent years and its indications are constantly expanding. The potential occurrence of intraoperative and postoperative neurovascular complications deserves special attention from neurosurgeons. Multimodal intraoperative neurophysiological monitoring technology allows neurosurgeons to monitor cerebral perfusion and the functional status of the associated cranial nerves in real time, thereby enabling surgeons to make prompt adjustments in surgical procedures and strategies and reduce the risks of postoperative neurological complications in patients. Based on available literature, we reviewed how appropriate monitoring strategies were optimized for different key components of transnasal endoscopic skull base procedures, intending to provide reference for clinicians.

The Research of Chinese Martial Arts Cross-Media Communication System Based on Deep Neural Network.

The spread of Chinese martial arts is crucial for the world to understand Chinese culture. If only relying on one transmission method, it will lead to the difference of transmission and its lack of certain real time. This will lead to differences in the understanding of Chinese martial arts, which is also not conducive to the spread of Chinese glorious culture. Cross-media communication technology can solve this communication difference problem very well. The deep neural network method was used to fuse relevant features of Chinese martial arts, and it also analyzes the feasibility of neural network technology in cross-media communication. At the same time, this study uses deep neural network to study the timeliness of Chinese martial arts in the process of cross-media communication. The research results show that the convolutional neural network can effectively extract the characteristics of Chinese martial arts and carry out effective dissemination. However, the hybrid convolutional neural network with temporal features has higher accuracy in extracting Chinese martial arts features. This hybrid convolutional neural network is more conducive to the dissemination of Chinese martial arts through cross-media technology, which can ensure its timeliness. The maximum error of deep neural network technology in predicting Chinese martial arts culture is only 2.67%. This part of the error comes from the action characteristics of Chinese martial arts culture, which shows that neural network technology has good feasibility.

Pigmented villonodular synovitis of the temporomandibular joint with skull base extension: a retrospective case series.

Most studies on pigmented villonodular synovitis (PVNS) of the temporomandibular joint (TMJ) with skull base extension mostly are case report. Here, we summarize the clinical features, treatments, and outcomes of PVNS of the TMJ with skull base extension in a large case series. We reviewed the clinical information relating to patients diagnosed with PVNS of the TMJ with skull base extension information of patients in our center between 2011 and 2020. We reviewed 10 patients (4 males and 6 females). All cases had presented with a unilateral lesion extending the middle skull base. PVNS of the TMJ with skull base extension occurred on the left side in 6 patients (60%) and on the right side in 4 patients (40%). Of the 10 patients, pain and mass were the most prevalent symptoms. All patients received surgery and no recurrence was seen after 35.90 ± 25.35 months follow-up. Despite destructive biological behavior, surgery can achieve an excellent outcome for patients with PVNS of the TMJ with skull base extension. An en bloc resection may prevent recurrence and provide long-term relief. Radiotherapy may be reserved for subtotal excision and recurrent lesions but require further investigation.

Correction: Pentacyclic spermidine alkaloids with radioprotective and anti-inflammatory activities from Orychophragmus violaceus.

Correction for 'Pentacyclic spermidine alkaloids with radioprotective and anti-inflammatory activities from Orychophragmus violaceus' by Zan-Xin Xu et al., Org. Biomol. Chem., 2021, 19, 9844-9848, DOI: 10.1039/D1OB01973B.

Risk factors for linezolid-induced thrombocytopenia in adult inpatients.

Background Previous reports about risk factors for linezolid-induced thrombocytopenia have been insufficient, often due to the variability in study design and population, and some factors have not yet been studied. Aim The aims of this study are to determine potential risk factors for linezolid-induced thrombocytopenia, and to analyze the influencing factors of different thrombocytopenia definitions. Method This retrospective study involved patients who were administered intravenous linezolid for ≥ 1 day between January 1, 2015 and January 1, 2021. Their demographic and clinical data were extracted from electronic medical records. Thrombocytopenia was defined as: ①thrombocytopenia with platelet count < 100 × 109/L and a decrease in 25% or more from baseline of the platelet count (criterion 1); ②thrombocytopenia due to a platelet count drop decrease of 25% or more from baseline (criterion 2). Risk factors were determined via binary logistic regression analysis. Results This study included 320 patients. Binary logistic regression analysis indicated that baseline platelet count (p < 0.001), linezolid therapy duration (p = 0.001) and shock (patients require vasoactive medications) (p = 0.019) were independent risk factors for criterion-1thrombocytopenia, while linezolid therapy duration (p < 0.001) and shock (p = 0.015) were independent risk factors for criterion-2 thrombocytopenia. There was also a significant correlation between shock and early-onset thrombocytopenia (p = 0.005 and 0.019 for criterion 1 and criterion 2, respectively). Conclusion Linezolid therapy duration and shock were common causes of different thrombocytopenia definitions; shock was correlated with early-onset thrombocytopenia. Platelet count should be monitored during linezolid therapy especially during long-duration therapy and in shock patients.