Ratiometric fluorescence and smartphone-assisted sensing platform based on dual-emission carbon dots for brilliant blue detection.

In this study, an innovative ratiometric fluorescence and smartphone-assisted visual sensing platform based on blue-yellow dual-emission carbon dots (BY-CDs) was constructed for the first time to determine brilliant blue. The BY-CDs was synthesized via a facile one-step hydrothermal process involving propyl gallate and o-phenylenediamine. The synthesized BY-CDs exhibit favorable water solubility and exceptional fluorescence stability. Under excitation at 370 nm, BY-CDs show two distinguishable fluorescence emission bands (458 and 558 nm). Upon addition of brilliant blue, the fluorescence intensity at 558 nm exhibited a significant quenching effect attributed to fluorescence resonance energy transfer (FRET), while the fluorescence intensity at 458 nm was basically unchanged. The prepared BY-CDs can effectively serve as a ratiometric nanosensor for determining brilliant blue with the ratio of fluorescence intensities at 458 and 558 nm (F458/F558) as response signal. In addition, the developed ratiometric fluorescence sensor exhibits a noticeable alteration in color from yellow to green under UV light with a wavelength of 365 nm upon addition of varying concentrations of brilliant blue, which provides the possibility of visual detection of brilliant blue by a smartphone application. Finally, the BY-CDs based dual-mode sensing platform successfully detected brilliant blue in actual food samples and achieved a desirable recovery rate. This study highlights the merits of fast, convenient, economical, real-time, visual, high accuracy, excellent precision, good selectivity and high sensitivity for brilliant blue detection, and paves new paths for the monitoring of brilliant blue in real samples.

Aptamer-Modified Nb2C Multifunctional Nanomedicine for Targeted Photothermal/Chemotherapy Combined Therapy of Tumor.

The poor delivery efficiency of nanotherapeutic drugs and their potential off-target toxicity significantly limit their effectiveness and extensive application. An active targeting system with high efficiency and few side effects is a promising strategy for tumor therapy. Herein, a multifunctional nanomedicine Nb2C-PAA-DOX@Apt-M (NDA-M) was constructed for targeted photothermal/chemotherapy (PTT/CHT) combined tumor therapy. The specific targeting ability of aptamer could effectively enhance the absorption of nanomedicine by the MCF-7 cell. By employing Apt-M, the NDA-M nanosheets demonstrated targeted delivery to MCF-7 cells, resulting in enhanced intracellular drug concentration. Under 1060 nm laser irradiation, a rapid temperature increase of the NDA-M was observed within the tumor region to achieve PTT. Meanwhile, CHT was triggered when DOX release was induced by photothermal/acid stimulation. The experimental results demonstrated that aptamer-mediated targeting achieved enhanced PTT/CHT efficacy both in vitro and in vivo. Notably, NDA-M induced complete ablation of solid tumors without any adverse side effects in mice. This study demonstrated new and promising tactics for the development of nanomaterials for targeted tumor therapy.

The Preparation of N, P-Doped NiSe Nanorod Electrode Materials on Nickel Foam Using the Microwave Method for High-Performance Supercapacitors.

Transition metal selenides have the leading position in the field of energy storage and conversion due to their high theoretical capacity, good electrical conductivity, and cycling stability. Nickel is widely used for the construction of positive electrodes in devices due to its good conductivity, variable valence state, and ideal redox activity. NiSe materials have high internal resistance and are prone to volume change during charging and discharging, thus affecting the practical application of this electrode material, and the reported NiSe materials have not achieved a more desirable capacity value. Therefore, in this study, N, P-NiSe nanoelectrode materials were prepared using nickel foam as the nickel source and hexachlorocyclotriphonitrile as the nitrogen and phosphorus dopant using an efficient, energy-saving, and simple microwave method. It was also characterised by XRD and XPS to confirm the successful preparation of N, P-NiSe materials. In addition, the material yielded a high capacitance value (3184 F g-1) and good cycling stability (72% of the initial capacitance value was retained after 4000 cycles) in electrochemical tests. To demonstrate its excellent suitability for practical applications, an asymmetric supercapacitor was assembled using N, P-NiSe as the anode and activated carbon as the cathode. At an operating voltage of 1.6 V, the device achieved an energy density of 289.06 Wh kg-1 and a power density of 799.26 W kg-1 and retained 80% of its initial capacity after 20,000 cycles.

A Dual-Recognition Fluorescence Enzyme-Linked Immunosorbent Assay for Specific Detection of Intact Lipid Nanoparticles via a Localized Scaffolding Autocatalytic DNA Circuit Amplifier.

Lipid nanoparticles (LNPs) are emerging as one of the most promising drug delivery systems. The long-circulating effect of intact LNPs (i-LNPs) is the key to efficacy and toxicity in vivo. However, the significant challenge is specific and sensitive detection of i-LNPs. Herein, a dual-recognition fluorescence enzyme-linked immunosorbent assay (DR-FELISA) was developed to directly isolate and detect i-LNPs by combining dual-recognition separation with a one-step signal amplification strategy. The microplates captured and enriched i-LNPs through antibody-antigen reaction. Dual-chol probes were spontaneously introduced into the lipid bilayer of captured i-LNPs, converting the detection of i-LNPs into the detection of double-cholesterol probes. Finally, the end of the dual-chol probes initiated the localized scaffolding autocatalytic DNA circuits (SADC) system for further signal amplification. The SADC system provides a sensitive and efficient amplifier through localized network structures and self-assembled triggers. Simultaneous recognition of i-LNPs surface PEG-lipid and lipid bilayer structures significantly eliminates interference from biological samples. i-LNPs were detected with high selectivity, ranging from 0.2 to 1.25 mg/mL with a limit of detection of 0.1 mg/mL. Moreover, this method allows the isolation and quantitative analysis of different formulations of i-LNPs in serum samples with a satisfactory recovery rate ranging from 94.8 to 116.3%. Thus, the DR-FELISA method provides an advanced platform for the exclusive and sensitive detection of i-LNPs, providing new insights for the study of the quality and intracorporal process of complex formulations.

Integrating hydrogels manipulate ECM deposition after spinal cord injury for specific neural reconnections via neuronal relays.

A bioinspired hydrogel composed of hyaluronic acid-graft-dopamine (HADA) and a designer peptide HGF-(RADA)4-DGDRGDS (HRR) was presented to enhance tissue integration following spinal cord injury (SCI). The HADA/HRR hydrogel manipulated the infiltration of PDGFRß+ cells in a parallel pattern, transforming dense scars into an aligned fibrous substrate that guided axonal regrowth. Further incorporation of NT3 and curcumin promoted axonal regrowth and survival of interneurons at lesion borders, which served as relays for establishing heterogeneous axon connections in a target-specific manner. Notable improvements in motor, sensory, and bladder functions resulted in rats with complete spinal cord transection. The HADA/HRR + NT3/Cur hydrogel promoted V2a neuron accumulation in ventral spinal cord, facilitating the recovery of locomotor function. Meanwhile, the establishment of heterogeneous neural connections across the hemisected lesion of canines was documented in a target-specific manner via neuronal relays, significantly improving motor functions. Therefore, biomaterials can inspire beneficial biological activities for SCI repair.

Application of dezocine patient-controlled epidural analgesia in postoperative analgesia in patients with total myomectomy.

BACKGROUND: Uterine fibroids are common benign gynecological conditions. Patients who experience excessive menstruation, anemia, and pressure symptoms should be administered medication, and severe cases require a total hysterectomy. This procedure is invasive and causes severe postoperative pain, which can affect the patient's postoperative sleep quality and, thus, the recovery process. AIM: To evaluate use of dezocine in patient-controlled epidural analgesia (PCEA) for postoperative pain management in patients undergoing total myomectomy. METHODS: We selected 100 patients undergoing total abdominal hysterectomy for uterine fibroids and randomized them into two groups: A control group receiving 0.2% ropivacaine plus 0.06 mg/mL of morphine and an observation group receiving 0.2% ropivacaine plus 0.3 mg/mL of diazoxide in their PCEA. Outcomes assessed included pain levels, sedation, recovery indices, PCEA usage, stress factors, and sleep quality. RESULTS: The observation group showed lower visual analog scale scores, shorter postoperative recovery indices, fewer mean PCEA compressions, lower cortisol and blood glucose levels, and better polysomnographic parameters compared to the control group (P < 0.05). The cumulative incidence of adverse reactions was lower in the observation group than in the control group (P < 0.05). CONCLUSION: Dezocine PCEA can effectively control the pain associated with total myomectomy, reduce the negative impact of stress factors, and have less impact on patients' sleep, consequently resulting in fewer adverse effects.

Next-to-Next-to-Leading-Order QCD Corrections to Pion Electromagnetic Form Factors.

We calculate the next-to-next-to-leading-order (NNLO) QCD radiative correction to the pion electromagnetic form factor with large momentum transfer. We explicitly verify the validity of the collinear factorization to two-loop order for this observable and obtain the respective IR-finite two-loop hard-scattering kernel in the closed form. The NNLO QCD correction turns out to be positive and significant. Incorporating this new ingredient of correction, we then make a comprehensive comparison between the finest theoretical predictions and numerous data for both space- and timelike pion form factors. Our phenomenological analysis provides a strong constraint on the second Gegenbauer moment of the pion light-cone distribution amplitude obtained from recent lattice QCD studies.

One-pot hydrothermal synthesis of silicon, nitrogen co-doped carbon dots for enhancing enzyme activity of acid phosphatase (ACP) to dopamine and for cell imaging.

Developing water-soluble nanomaterials with high photoluminescence emission and high yield for biological analysis and imaging is urgently needed. Herein, water-soluble blue emitting silicon and nitrogen co-doped carbon dots (abbreviated as Si-CDs) of a high photoluminescence quantum yield of 80 % were effectively prepared with high yield rate (59.1 %) via one-step hydrothermal treatment of N-[3-(trimethoxysilyl)propyl]ethylenediamine (DAMO) and trans-aconitic acid. Furthermore, the Si-CDs demonstrate environmental robustness, photo-stability and biocompatibility. Given the importance of the potentially abnormal levels of acid phosphatase (ACP) in cancer diagnosis, developing a reliable and sensitive ACP measurement method is of significance for clinical research. The Si-CDs unexpectedly promote the catalytic oxidation of ACP on dopamine (DA) to polydopamine under acidic conditions through the produced reactive oxygen species (ROS). Correspondingly, a fluorescence response strategy using Si-CDs as the dual functions of probes and promoting enzyme activity of ACP on catalyzing DA was constructed to sensitively determine ACP. The quantitative analysis of ACP displayed a linear range of 0.1-60 U/L with a detection limit of 0.056 U/L. The accurate detection of ACP was successfully achieved in human serum through recovery tests. As a satisfactory fluorescent probe, Si-CDs were successfully applied to fluorescent imaging of A549 cells in cytoplasmic with long-term and safe staining. The Si-CDs have the dual properties of outstanding fluorescent probes and auxiliary oxidase activity, indicating their great potential in multifunctional applications.

A Cysteinyl-tRNA Synthetase Mutation Causes Novel Autosomal-Dominant Inheritance of a Parkinsonism/Spinocerebellar-Ataxia Complex.

This study aimed to identify possible pathogenic genes in a 90-member family with a rare combination of multiple neurodegenerative disease phenotypes, which has not been depicted by the known neurodegenerative disease. We performed physical and neurological examinations with International Rating Scales to assess signs of ataxia, Parkinsonism, and cognitive function, as well as brain magnetic resonance imaging scans with seven sequences. We searched for co-segregations of abnormal repeat-expansion loci, pathogenic variants in known spinocerebellar ataxia-related genes, and novel rare mutations via whole-genome sequencing and linkage analysis. A rare co-segregating missense mutation in the CARS gene was validated by Sanger sequencing and the aminoacylation activity of mutant CARS was measured by spectrophotometric assay. This pedigree presented novel late-onset core characteristics including cerebellar ataxia, Parkinsonism, and pyramidal signs in all nine affected members. Brain magnetic resonance imaging showed cerebellar/pons atrophy, pontine-midline linear hyperintensity, decreased rCBF in the bilateral basal ganglia and cerebellar dentate nucleus, and hypo-intensities of the cerebellar dentate nuclei, basal ganglia, mesencephalic red nuclei, and substantia nigra, all of which suggested neurodegeneration. Whole-genome sequencing identified a novel pathogenic heterozygous mutation (E795V) in the CARS gene, meanwhile, exhibited none of the known repeat-expansions or point mutations in pathogenic genes. Remarkably, this CARS mutation causes a 20% decrease in aminoacylation activity to charge tRNACys with L-cysteine in protein synthesis compared with that of the wild type. All family members carrying a heterozygous mutation CARS (E795V) had the same clinical manifestations and neuropathological changes of Parkinsonism and spinocerebellar-ataxia. These findings identify novel pathogenesis of Parkinsonism-spinocerebellar ataxia and provide insights into its genetic architecture.

Detection of Reactive Oxygen Species in Plant Root Immunity.

Reactive oxygen species (ROS) production is a key early defense mechanism in plants when exposed to biotic stress. Upon recognition of conserved microbe-associated molecular patterns (MAMPs) from pathogens by plant receptors, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases in the plasma membrane are activated to produce hydrogen peroxide (H2O2). This, in turn, regulates multiple signaling pathways to trigger immunity and suppress pathogen infection. Monitoring the ROS burst in plant leaves can be done within minutes of MAMPs treatment. However, there is limited research on the quantification of ROS production in plant root tissues during the activation of plant immunity. In this study, we introduce a rapid, accessible, and straightforward technique for measuring MAMPs-triggered ROS bursts in the roots of the model legume Medicago truncatula. This method will facilitate the investigation of plant root responses to biotic and abiotic stresses.

The molecular signature and prognosis of glioma with preoperative intratumoral hemorrhage: a retrospective cohort analysis.

BACKGROUND: Intratumoral hemorrhage, though less common, could be the first clinical manifestation of glioma and is detectable via MRI; however, its exact impacts on patient outcomes remain unclear and controversial. The 2021 WHO CNS 5 classification emphasised genetic and molecular features, initiating the necessity to establish the correlation between hemorrhage and molecular alterations. This study aims to determine the prevalence of intratumoral hemorrhage in glioma subtypes and identify associated molecular and clinical characteristics to improve patient management. METHODS: Integrated clinical data and imaging studies of patients who underwent surgery at the Department of Neurosurgery at Peking Union Medical College Hospital from January 2011 to January 2022 with pathological confirmation of glioma were retrospectively reviewed. Patients were divided into hemorrhage and non-hemorrhage groups based on preoperative magnetic resonance imaging. A comparison and survival analysis were conducted with the two groups. In terms of subgroup analysis, we classified patients into astrocytoma, IDH-mutant; oligodendroglioma, IDH-mutant, 1p/19q-codeleted; glioblastoma, IDH-wildtype; pediatric-type gliomas; or circumscribed glioma using integrated histological and molecular characteristics, according to WHO CNS 5 classifications. RESULTS: 457 patients were enrolled in the analysis, including 67 (14.7%) patients with intratumoral hemorrhage. The hemorrhage group was significantly older and had worse preoperative Karnofsky performance scores. The hemorrhage group had a higher occurrence of neurological impairment and a higher Ki-67 index. Molecular analysis indicated that CDKN2B, KMT5B, and PIK3CA alteration occurred more in the hemorrhage group (CDKN2B, 84.4% vs. 62.2%, p = 0.029; KMT5B, 25.0% vs. 8.9%, p = 0.029; and PIK3CA, 81.3% vs. 58.5%, p = 0.029). Survival analysis showed significantly worse prognoses for the hemorrhage group (hemorrhage 18.4 months vs. non-hemorrhage 39.1 months, p = 0.01). In subgroup analysis, the multivariate analysis showed that intra-tumoral hemorrhage is an independent risk factor only in glioblastoma, IDH-wildtype (162 cases of 457 overall, HR = 1.72, p = 0.026), but not in other types of gliomas. The molecular alteration of CDK6 (hemorrhage group p = 0.004, non-hemorrhage group p < 0.001), EGFR (hemorrhage group p = 0.003, non-hemorrhage group p = 0.001), and FGFR2 (hemorrhage group p = 0.007, non-hemorrhage group p = 0.001) was associated with shorter overall survival time in both hemorrhage and non-hemorrhage groups. CONCLUSIONS: Glioma patients with preoperative intratumoral hemorrhage had unfavorable prognoses compared to their nonhemorrhage counterparts. CDKN2B, KMT5B, and PIK3CA alterations were associated with an increased occurrence of intratumoral hemorrhage, which might be future targets for further investigation of intratumoral hemorrhage.

Macrophage interleukin-1ß mediates atrial fibrillation risk in diabetic mice.

Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF). The mechanisms underlying DM-associated AF are unclear. AF and DM are both related to inflammation. We investigated whether DM-associated inflammation contributed to AF risk. Mice were fed with high fat diet to induce type II DM and were subjected to IL-1ß antibodies, macrophage depletion by Clodronate liposomes, a mitochondrial antioxidant (mitoTEMPO), or a cardiac ryanodine receptor (RyR2) stabilizer (S107). All tests were performed at 36-38 weeks of age. DM mice presented with increased AF inducibility, enhanced mitochondrial reactive oxygen species (mitoROS) generation, and activated innate immunity in the atria as evidenced by enhanced monocyte chemoattractant protein-1 (MCP-1) expression, macrophage infiltration, and IL-1ß levels. Signs of aberrant RyR2 Ca2+ leak were observed in the atria of DM mice. IL-1ß neutralization, macrophage depletion, mitoTEMPO, and S107 significantly ameliorated the AF vulnerability in DM mice. Atrial overexpression of MCP-1 increased AF occurrence in normal mice through the same mechanistic signaling cascade as observed in DM mice. In conclusion, macrophage-mediated IL-1ß contributed to DM-associated AF risk through mitoROS modulation of RyR2 Ca2+ leak.

Non-invasive prediction of preeclampsia using the maternal plasma cell-free DNA profile and clinical risk factors.

Background: Preeclampsia (PE) is a pregnancy complication defined by new onset hypertension and proteinuria or other maternal organ damage after 20 weeks of gestation. Although non-invasive prenatal testing (NIPT) has been widely used to detect fetal chromosomal abnormalities during pregnancy, its performance in combination with maternal risk factors to screen for PE has not been extensively validated. Our aim was to develop and validate classifiers that predict early- or late-onset PE using the maternal plasma cell-free DNA (cfDNA) profile and clinical risk factors. Methods: We retrospectively collected and analyzed NIPT data of 2,727 pregnant women aged 24-45 years from four hospitals in China, which had previously been used to screen for fetal aneuploidy at 12 + 0 ~ 22 + 6 weeks of gestation. According to the diagnostic criteria for PE and the time of diagnosis (34 weeks of gestation), a total of 143 early-, 580 late-onset PE samples and 2,004 healthy controls were included. The wilcoxon rank sum test was used to identify the cfDNA profile for PE prediction. The Fisher's exact test and Mann-Whitney U-test were used to compare categorical and continuous variables of clinical risk factors between PE samples and healthy controls, respectively. Machine learning methods were performed to develop and validate PE classifiers based on the cfDNA profile and clinical risk factors. Results: By using NIPT data to analyze cfDNA coverages in promoter regions, we found the cfDNA profile, which was differential cfDNA coverages in gene promoter regions between PE and healthy controls, could be used to predict early- and late-onset PE. Maternal age, body mass index, parity, past medical histories and method of conception were significantly differential between PE and healthy pregnant women. With a false positive rate of 10%, the classifiers based on the combination of the cfDNA profile and clinical risk factors predicted early- and late-onset PE in four datasets with an average accuracy of 89 and 80% and an average sensitivity of 63 and 48%, respectively. Conclusion: Incorporating cfDNA profiles in classifiers might reduce performance variations in PE models based only on clinical risk factors, potentially expanding the application of NIPT in PE screening in the future.

Molecular Mechanism of Sevoflurane Affecting Fetal Nervous System's Development Through the GABAAR/Sirt 1 Pathway.

Objective: To investigate the molecular mechanism of sevoflurane affecting the development of the offspring's nervous system through the GABAAR/Sirt 1 pathway. Methods: Pregnant rats were obtained by mating females and males, and were randomly divided into 3 h sevoflurane (2.3% sevoflurane anesthesia for 3 h), 6 h sevoflurane (2.3% sevoflurane anesthesia for 6 h), Sirt-1 activator-SRT1720 (10 mg/kg SRT1720), 6 h sevoflurane+SRT1720 (10 mg/kg SRT1720) and control groups) group and control group, 31-day-old littermates were taken out and their learning and memory functions were examined by the water maze experiment; the heads were severed to remove the brains, and the kits were used to detect the levels of 5-HT and Ach in the brain tissue; the hippocampal tissues of the littermates were isolated, and neuronal damage in the hippocampal tissues was assessed by Nissen staining; neuronal apoptosis in the hippocampal tissues was detected by TUNEL staining; and GABAAR in the hippocampal tissues was detected by Western blot. GABAAR, Sirt-1, and apoptosis-related proteins (Caspase-3, BCL-2, BAX) in hippocampal tissue. Results: Compared with the control group, the 3 h sevoflurane group and the 6 h sevoflurane group neurons were arranged sparsely, the cells appeared to be swollen, the evasion latency, the apoptosis rate of neurons, the expression of Caspase-3, and BAX increased significantly, and the number of crossing the plateau, the level of 5-HT and Ach in the brain tissues, and the expression of GABAAR, Sirt-1, and BCL-2 were decreased significantly, and the differences existed between the groups (P < .5); compared with the 6 h sevoflurane group, neuronal morphological changes in the hippocampal tissue of the 6 h sevoflurane+SRT1720 group were improved, with a significant decrease in the evasion latency, neuronal apoptosis rate, expression of Caspase-3 and BAX, and a significant increase in the number of traversing platforms, brain tissue 5-HT, Ach level, GABAAR, Sirt-1, and BCL-2 expression (P < .5); compared with the SRT1720 group, the neurons in the 6 h sevoflurane + SRT1720 group were sparsely arranged, with a significant increase in evasion latency, neuronal apoptosis rate, caspase-3, BAX expression, and a significant decrease in the number of traversing platforms, brain tissue 5-HT, Ach level, GABAAR, Sirt-1, and BCL-2 expression (P < .5 ). Conclusion: Sevoflurane can affect the neurological development of rat offspring, which may be related to the inhibition of Sirt-1 expression.

Phase 1 study of safety and preliminary efficacy of intranasal transplantation of human neural stem cells (ANGE-S003) in Parkinson's disease.

BACKGROUND: Intranasal transplantation of ANGE-S003 human neural stem cells showed therapeutic effects and were safe in preclinical models of Parkinson's disease (PD). We investigated the safety and tolerability of this treatment in patients with PD and whether these effects would be apparent in a clinical trial. METHODS: This was a 12-month, single-centre, open-label, dose-escalation phase 1 study of 18 patients with advanced PD assigned to four-time intranasal transplantation of 1 of 3 doses: 1.5 million, 5 million or 15 million of ANGE-S003 human neural stem cells to evaluate their safety and efficacy. RESULTS: 7 patients experienced a total of 14 adverse events in the 12 months of follow-up after treatment. There were no serious adverse events related to ANGE-S003. Safety testing disclosed no safety concerns. Brain MRI revealed no mass formation. In 16 patients who had 12-month Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) data, significant improvement of MDS-UPDRS total score was observed at all time points (p<0.001), starting with month 3 and sustained till month 12. The most substantial improvement was seen at month 6 with a mean reduction of 19.9 points (95% CI, 9.6 to 30.3; p<0.001). There was no association between improvement in clinical outcome measures and cell dose levels. CONCLUSIONS: Treatment with ANGE-S003 is feasible, generally safe and well tolerated, associated with functional improvement in clinical outcomes with peak efficacy achieved at month 6. Intranasal transplantation of neural stem cells represents a new avenue for the treatment of PD, and a larger, longer-term, randomised, controlled phase 2 trial is warranted for further investigation.

Pyrolysis mechanism and pyrolysis kinetics of yellow wine lees.

Yellow wine lees, a by-product produced while brewing yellow wine, can be a helpful biomass resource through pyrolysis. However, there have been very few studies on the pyrolysis of yellow wine lees. The kinetics and mechanism of pyrolysis in yellow wine lees were explored through an extensive study of their chemical and elemental composition. The pyrolysis mechanism of yellow wine lees was further studied using thermogravimetric analysis (TGA) from 30 °C to 900 °C. The TG/DTG analysis showed that yellow wine lees thermally decomposed mainly between 121 °C and 500 °C. The maximum decomposition was observed between 218 °C and 326 °C, with a clear peak at 298 °C. Upon analyzing the 3D-FTIR results, the gas phase products at this stage primarily included inorganic molecules like CO2, H2O, and CH4, along with organic compounds such as esters, alcohols, phenols, amines, ethers, aldehydes, ketones, and acids. The Maillard reaction and ketosis decarboxylation primarily occurred in proteins (amino acids) and carbohydrates. The pyrolysis kinetics of yellow wine lees were analyzed utilizing the distributed activation energy model (DAEM). The results of DAEM were simultaneously verified using the Flynn-Wall-Ozawa (FWO) method. The findings indicated that the pyrolysis of yellow wine lees conforms to the assumptions of infinite parallel reactions and activation energy distribution. As the conversion rate increased during pyrolysis, the activation energy of yellow wine lees initially increased to 210-220 kJ mol-1, then stabilized at 190-200 kJ mol-1 and rapidly decreased to approximately 100 kJ mol-1. This study offers a theoretical basis for the application of yellow wine lees using pyrolysis.

Discovery of 4-benzylpiperazinequinoline BChE inhibitor that suppresses neuroinflammation for the treatment of Alzheimer's disease.

Butyrylcholinesterase (BChE) has attracted wide interest as a promising target in Alzheimer's disease (AD) investigation. BChE is considered to play a compensable role of hydrolyzing acetylcholine (ACh), and its positive correlation with ß-amyloid (Aß) deposition also promotes disease progression. Herein, we uncovered a selective potent BChE inhibitor S21-1011 (eqBChE IC50 = 0.059 ± 0.006 µM, hBChE IC50 = 0.162 ± 0.069 µM), which presented satisfactory druggability and therapeutic efficacy in AD models. In pharmacokinetics (PK) studies, S21-1011 showed excellent blood-brain barrier (BBB) permeability, metabolism stability and high oral-bioavailability. In pharmacodynamic (PD) studies, it protected neural cells from toxicity and inflammation stimulation in vitro. Besides, it also exerted anti-inflammatory effect and alleviated cognitive impairment in mice models induced by lipopolysaccharides (LPS) and Aß. Generally, this compound has been confirmed to function as a neuroprotector and cognition improver in various AD pathology-like models. Therefore, S21-1011, a novel potent BChE inhibitor, could be considered as a potential anti-AD candidate worthy of more profound investigation.

Exploring cerebral structural and functional abnormalities in a mouse model of post-traumatic headache induced by mild traumatic brain injury.

Mild traumatic brain injury (mTBI)-induced post-traumatic headache (PTH) is a pressing public health concern and leading cause of disability worldwide. Although PTH is often accompanied by neurological disorders, the exact underlying mechanism remains largely unknown. Identifying potential biomarkers may prompt the diagnosis and development of effective treatments for mTBI-induced PTH. In this study, a mouse model of mTBI-induced PTH was established to investigate its effects on cerebral structure and function during short-term recovery. Results indicated that mice with mTBI-induced PTH exhibited balance deficits during the early post-injury stage. Metabolic kinetics revealed that variations in neurotransmitters were most prominent in the cerebellum, temporal lobe/cortex, and hippocampal regions during the early stages of PTH. Additionally, variations in brain functional activities and connectivity were further detected in the early stage of PTH, particularly in the cerebellum and temporal cortex, suggesting that these regions play central roles in the mechanism underlying PTH. Moreover, our results suggested that GABA and glutamate may serve as potential diagnostic or prognostic biomarkers for PTH. Future studies should explore the specific neural circuits involved in the regulation of PTH by the cerebellum and temporal cortex, with these two regions potentially utilized as targets for non-invasive stimulation in future clinical treatment.

Identification and optimization of nitrophenolic analogues as dopamine metabolic enzyme inhibitors for the treatment of Parkinson's disease.

Progressive loss of dopaminergic neurons leads to the depletion of the striatal neurotransmitter dopamine, which is the main cause of Parkinson's disease (PD) motor symptoms. Simultaneous inhibition of the two key dopamine metabolic enzymes, catechol-O-methyltransferase (COMT) and monoamine oxidase B (MAO-B), could potentially be a breakthrough in achieving clinical efficacy. Representative compound C12 exhibits good COMT inhibitory activity (IC50 = 0.37 µM), metal chelation ability, and BBB permeability. Furthermore, results from in vivo biological activity evaluations indicate that C12 can improve dopamine levels and ameliorate MPTP-induced PD symptoms in mice. Preliminary in vivo and in vitro study results highlight the potential of compound C12 in PD treatment.