T-antigen as a biomarker of progression-free survival in patients with glioblastoma.

OBJECTIVE: Glioblastoma (GBM) is one of the most aggressive brain tumors and often leads to poor outcomes. Studies have indicated that glycan levels are significantly correlated with the pathogenesis and development of cancers. However, whether glycan levels can serve as diagnostic or prognostic biomarkers in GBM remains unclear. METHODS: We obtained glycomic profiles in tissue and serum samples from 55 individuals with GBM using a well-established lectin biochip platform probing with 11 specific lectins. RESULTS: Our univariate analysis showed that 5 out of the 11 lectin-probed glycans (LPGs) were significantly higher in GBM tissues than in peri-tumoral tissues. After logistic regression analyses, only the Jacalin-probed T-antigen difference between the two groups remained significant (p = 0.037). Moreover, survival-related analyses showed that the level of Jacalin-probed T-antigen was significantly associated with the progression-free survival (p = 0.038) of patients. However, none of the LPG levels were correlated with the overall survival or the chemosensitivity to temozolomide therapy. The correlation coefficient analysis showed a moderate-to-strong correlation in the Jacalin-probed T-antigen levels between GBM tissues and serum samples, indicating its potential usefulness as a non-invasive GBM progression biomarker. INTERPRETATION: Glycomics analyses can be helpful in the prediction of GBM recurrences and may provide information useful for GBM glycan-based target therapies or vaccine development.

Deep brain stimulation of the subthalamic nucleus for a patient with drug resistant juvenile myoclonic epilepsy: 1 year follow-up.

BACKGROUND: Drug-resistant juvenile myoclonic epilepsy (DR-JME) remains a significant challenge in neurology. Traditional management strategies often fail to achieve satisfactory control, necessitating innovative treatments. OBJECTIVE: This case report aims to evaluate the efficacy and safety of deep brain stimulation (DBS) targeting the subthalamic nucleus (STN-DBS) in a patient with DR-JME. METHODS: We describe the treatment of a patient with DR-JME using STN-DBS. The patient underwent implantation and received high-frequency stimulation (HFS) at the STN. RESULTS: One year post-implantation, the patient demonstrated a substantial reduction in motor seizure frequency by 87.5%, with improvements in quality of life and seizure severity by 52.0% and 46.7%, respectively. No adverse events were reported during the follow-up period. CONCLUSIONS: This case represents the first report of favorable outcomes with STN-DBS in a patient with DR-JME, suggesting that long-term HFS of the STN may be a promising treatment option for patients suffering from this condition.

Synthesis and Properties of A Strained Triple Nanohoop.

A strained triple nanohoop with a shared central benzene unit is synthesized using a threefold intramolecular ring-closing approach. Among the five possible constitutional isomers, the isomer with the highest D3h symmetry is isolated, the structure of which contains three nanohoop blades and a central hexaphenylbenzene unit. The structure is elucidated using NMR spectroscopy and mass spectrometry. The optical and electrochemical properties are investigated, revealing a moderate fluorescence quantum yield of 40%. A water-soluble nanomaterial is prepared using a nanoparticle encapsulation method, and a fluorescence quantum yield of 10% is retained, which demonstrates the potential of the nanomaterial in biological systems.

Unveiling structure and performance of tea-derived cellulose nanocrystals.

In this study, cellulose was extracted from black tea residues to produce black tea cellulose nanocrystals (BT-CNCs) using an optimized acid hydrolysis method. The structure and performance of BT-CNCs were evaluated. The results showed that the optimal conditions for acidolysis of BT-CNCs included a sulfuric acid concentration of 64 %, a solid-liquid ratio of 1:18 (w/v), a hydrolysis temperature of 45 °C, and a hydrolysis time of 50 min. The optimization process resulted in a 44.8 % increase in the yield of BT-CNCs, which exhibited a crystallinity of 68.57 % and were characterized by the typical cellulose I structure. The diameters of the particles range from 5 to 45 nm, and they exhibit aggregation behavior. Notably, BT-CNCs demonstrated excellent storage stability, and the Tyndall effect occurred when exposed to a single beam of light. Although the thermal stability of BT-CNCs decreased, their primary thermal degradation temperature remained above 200 °C. The colloidal nature of BT-CNCs was identified as a non-Newtonian fluid with "shear thinning" behavior. This study introduces a novel method to convert tea waste into BT-CNCs, increasing the yield of BT-CNCs and enhancing waste utilization. BT-CNCs hold promise for application in reinforced composites, offering substantial industrial value.

Synapse Neurotransmitter Channel-Inspired AlOx Memristor with "V" Type Oxygen Vacancy Distribution.

Memristor possesses great potential and advantages in neuromorphic computing, while consistency and power consumption issues have been hindering its commercialization. Low cost and accuracy are the advantages of human brain, so memristors can be used to construct brain-like synaptic devices to solve these problems. In this work, a five-layer AlOx device with a V-shaped oxygen distribution is used to simulate biological synapses. The device simulates synapse structurally. Further, under electrical stimulation, O2- moves to the Ti electrode and oxygen vacancy (Vo) moves to the Pt electrode, thus forming a conductive filament (CF), which simulates the Ca2+ flow and releases neurotransmitters to the postsynaptic membrane, thus realizing the transmission of information. By controlling applied voltage, the regulation of Ca2+ gated pathway is realized to control the Ca2+ internal flow and achieve different degrees of information transmission. Long-term Potentiation (LTP)/Long-term Depression (LTD), Spike Timing Dependent Plasticity (STDP), these basic synaptic performances can be simulated. The AlOx device realizes low power consumption (56.7 pJ/392 fJ), high switching speed (25 ns/60 ns), and by adjusting the window value, the nonlinearity is improved (0.133/0.084), a high recognition accuracy (98.18%) is obtained in neuromorphic simulation. It shows a great prospect in multi-value storage and neuromorphic computing.

Health Status of Nonemergency Patients in the Emergency Department Using the EQ-5D.

Background: Emergency department (ED) overcrowding is influenced by several factors including the hospital's capacity, staff, patient discharges, and community resources. The number of annual ED visits has increased, with patients' medical needs exceeding emergency capacity, resulting in a widespread concern about emergency room overcrowding. Nonemergency patients tend to use large amounts of emergency medical resources, which is one reason for ED overcrowding. Most patients consider their medical cases urgent, whereas medical professionals consider many cases to be nonemergency. Only a few studies have examined self-rated health among nonemergency patients. Methods: This cross-sectional study was conducted in the ED of a tertiary hospital in China using the European Quality of Life Five-Dimensional Questionnaire to investigate the health status of nonemergency patients. Results: Among the 545 respondents, 246 (45.14%) self-assessed their health as excellent, 186 (34.13%) as very good, 70 (12.84%) as good, 32 (5.87%) as average, and 11 (2.02%) as poor. Problems related to pain/discomfort were reported by 317 (58.17%) participants, 214 (39.27%) responded that they had problems related to daily activities, 212 (38.90%) responded that they felt anxious or depressed, 211 (38.35%) responded that they had problems related to self-care, and some or extreme problems related to mobility were stated by 193 people (35.41%). Conclusions: Nonemergency patients generally reported good health. Pain/discomfort was the most significant factor affecting the health of nonemergency patients, followed by limitation of daily activities. The duration of illness onset and self-rated health status were common factors influencing the health status of nonemergency patients. This trial is registered with ChiCTR1900023578.

Photochemical Transformation of Monochloramine Induced by Triplet State Dissolved Organic Matter.

The photoexcited dissolved organic matter (DOM) could produce reactive intermediates, affecting chemical oxidant transformation in UV based advanced oxidation processes (AOPs). This study confirmed the critical role of triplet state DOM (3DOM*), generated from DOM photoexcitation, in the transformation of monochloramine (NH2Cl), a commonly used chemical oxidant and disinfectant in water treatment. NH2Cl (42.25 µM, as Cl2) was decayed by 17.4-73.4 % within 60 min, primarily due to 3DOM* , in DOM (2-30 mgC L-1) solutions irradiated by 365 nm, where NH2Cl has no absorption. The second-order quenching rate constants of triplet state model photosensitizers by NH2Cl were determined to be 0.95(± 0.04)-4.49(± 0.04)× 108 M-1 s-1 by using laser flash photolysis. As a reductant, 3DOM* reacted with NH2Cl through one-transfer mechanism, leading to amino radical (NH2•) generation, which then transferred to ammonia (NH4+, pKa 9.25) through H-abstraction by the phenolic moieties in DOM. Additionally, the intermediate product of 3DOM* oxidized by NH2Cl or those triplet state quinones can hydrolyze to form phenolic moieties, elevating NH4+ yield to higher than 99% upon 365 nm irradiation. These findings suggest that the widespread DOM can be applied to convert NH2Cl via 3DOM* with minimal toxic risks.

Carbon-chain length determines the binding affinity and inhibitory strength of per- and polyfluoroalkyl substances on human and rat steroid 5α-reductase 1 activity.

Per- and polyfluoroalkyl substances (PFAS) are widely used synthetic chemicals that persist in the environment and bioaccumulate in animals and humans. There is growing evidence that PFAS exposure adversely impacts neurodevelopment and neurological health. Steroid 5α-reductase 1 (SRD5A1) plays a key role in neurosteroidogenesis by catalyzing the conversion of testosterone or pregnenolone to neuroactive steroids, which influence neural development, cognition, mood, and behavior. This study investigated the inhibitory strength and binding interactions of 18 PFAS on human and rat SRD5A1 activity using enzyme assays, molecular docking, and structure-activity relationship analysis. Results revealed that C9-C14 PFAS carboxylic acid at 100 µM significantly inhibited human SRD5A1, with IC50 values ranged from 10.99 µM (C11) to 105.01 µM (C14), and only one PFAS sulfonic acid (C8S) significantly inhibited human SRD5A1 activity, with IC50 value of 8.15 µM. For rat SRD5A1, C9-C14 PFAS inhibited rat SRD5A1, showing the similar trend, depending on carbon number of the carbon chain. PFAS inhibit human and rat SRD5A1 in a carbon chain length-dependent manner, with optimal inhibition around C11. Kinetic studies indicated PFAS acted through mixed inhibition. Molecular docking revealed PFAS bind to the domain between NADPH and testosterone binding site of both SRD5A1 enzymes. Inhibitory potency correlated with physicochemical properties like carbon number of the carbon chain. These findings suggest PFAS may disrupt neurosteroid synthesis and provide insight into structure-based inhibition of SRD5A1.

S-Shaped Helical Singlet Diradicaloid and Its Transformation to Circumchrysene via a Two-Stage Cyclization.

Polycyclic hydrocarbons with diradical and polyradical characters usually display unique reactivities in ring-cyclization reactions. However, such reactions are rarely used to construct π-extended polycyclic aromatic hydrocarbons. Here, we describe the synthesis of an S-shaped doubly helical singlet diradicaloid compound and its facile transformation into an unprecedented circumchrysene via a two-stage ring cyclization, which includes: (1) an eletrocylization from diradicaloid precursor and (2) a Scholl reaction. The reaction mechanism was investigated through in situ spectroscopic studies, assisted by theoretical calculations. This reaction sequence yields an optically resolved π-extended [5]helicene derivative with a fluorescence quantum yield up to 85% and a circularly polarized luminescence brightness up to 6.05 M-1 cm-1 in the far-red to near-infrared regions. This sequence also yielded a highly delocalized circumchrysene molecule, exhibiting large electron delocalization, moderate fluorescence quantum yield, and multistage redox properties.

Decreased Electrically and Increased Ionically Conducting Scaffolds for Long-Life, High-Rate and Deep-Capacity Lithium-Metal Anodes.

Lithium (Li) metal batteries are deemed as promising next-generation power solutions but are hindered by the uncontrolled dendrite growth and infinite volume change of Li anodes. The extensively studied 3D scaffolds as solutions generally lead to undesired "top-growth" of Li due to their high electrical conductivity and the lack of ion-transporting pathways. Here, by reducing electrical conductivity and increasing the ionic conductivity of the scaffold, the deposition spot of Li to the bottom of the scaffold can be regulated, thus resulting in a safe bottom-up plating mode of the Li and dendrite-free Li deposition. The resulting symmetrical cells with these scaffolds, despite with a limited pre-plated Li capacity of 5 mAh cm-2, exhibit ultra-stable Li plating/stripping for over 1 year (11 000 h) at a high current density of 3 mA cm-2 and a high areal capacity of 3 mAh cm-2. Moreover, the full cells with these scaffolds further demonstrate high cycling stability under challenging conditions, including high cathode loading of 21.6 mg cm-2, low negative-to-positive ratio of 1.6, and limited electrolyte-to-capacity ratio of 4.2 g Ah-1.

High-performance fibre battery with polymer gel electrolyte.

Replacement of liquid electrolytes with polymer gel electrolytes is recognized as a general and effective way of solving safety problems and achieving high flexibility in wearable batteries1-6. However, the poor interface between polymer gel electrolyte and electrode, caused by insufficient wetting, produces much poorer electrochemical properties, especially during the deformation of the battery7-9. Here we report a strategy for designing channel structures in electrodes to incorporate polymer gel electrolytes and to form intimate and stable interfaces for high-performance wearable batteries. As a demonstration, multiple electrode fibres were rotated together to form aligned channels, while the surface of each electrode fibre was designed with networked channels. The monomer solution was effectively infiltrated first along the aligned channels and then into the networked channels. The monomers were then polymerized to produce a gel electrolyte and form intimate and stable interfaces with the electrodes. The resulting fibre lithium-ion battery (FLB) showed high electrochemical performances (for example, an energy density of about 128 Wh kg-1). This strategy also enabled the production of FLBs with a high rate of 3,600 m h-1 per winding unit. The continuous FLBs were woven into a 50 cm × 30 cm textile to provide an output capacity of 2,975 mAh. The FLB textiles worked safely under extreme conditions, such as temperatures of -40 °C and 80 °C and a vacuum of -0.08 MPa. The FLBs show promise for applications in firefighting and space exploration.

Discovery of a Novel Orally Bioavailable FLT3-PROTAC Degrader for Efficient Treatment of Acute Myeloid Leukemia and Overcoming Resistance of FLT3 Inhibitors.

Fms-like tyrosine receptor kinase 3 (FLT3) proteolysis-targeting chimeras (PROTACs) represent a promising approach to eliminate the resistance of FLT3 inhibitors. However, due to the poor druggability of PROTACs, the development of orally bioavailable FLT3-PROTACs faces great challenges. Herein, a novel orally bioavailable FLT3-ITD degrader A20 with excellent pharmacokinetic properties was discovered through reasonable design. A20 selectively inhibited the proliferation of FLT3-ITD mutant acute myeloid leukemia (AML) cells and potently induced FLT3-ITD degradation through the ubiquitin-proteasome system. Notably, oral administration of A20 resulted in complete tumor regression on subcutaneous AML xenograft models. Furthermore, on systemic AML xenograft models, A20 could completely eliminate the CD45+CD33+ human leukemic cells in murine and significantly prolonged the survival time of mice. Most importantly, A20 exerted significantly improved antiproliferative activity against drug-resistant AML cells compared to existing FLT3 inhibitors. These findings suggested that A20 could serve as a promising drug candidate for relapsed or refractory AML.

Matrix metallopeptidase 9 contributes to the beginning of plaque and is a potential biomarker for the early identification of atherosclerosis in asymptomatic patients with diabetes.

Aims: To determine the roles of matrix metallopeptidase-9 (MMP9) on human coronary artery smooth muscle cells (HCASMCs) in vitro, early beginning of atherosclerosis in vivo in diabetic mice, and drug naïve patients with diabetes. Methods: Active human MMP9 (act-hMMP9) was added to HCASMCs and the expressions of MCP-1, ICAM-1, and VCAM-1 were measured. Act-hMMP9 (n=16) or placebo (n=15) was administered to diabetic KK.Cg-Ay/J (KK) mice. Carotid artery inflammation and atherosclerosis measurements were made at 2 and 10 weeks after treatment. An observational study of newly diagnosed drug naïve patients with type 2 diabetes mellitus (T2DM n=234) and healthy matched controls (n=41) was performed and patients had ultrasound of carotid arteries and some had coronary computed tomography angiogram for the assessment of atherosclerosis. Serum MMP9 was measured and its correlation with carotid artery or coronary artery plaques was determined. Results: In vitro, act-hMMP9 increased gene and protein expressions of MCP-1, ICAM-1, VCAM-1, and enhanced macrophage adhesion. Exogenous act-hMMP9 increased inflammation and initiated atherosclerosis in KK mice at 2 and 10 weeks: increased vessel wall thickness, lipid accumulation, and Galectin-3+ macrophage infiltration into the carotid arteries. In newly diagnosed T2DM patients, serum MMP9 correlated with carotid artery plaque size with a possible threshold cutoff point. In addition, serum MMP9 correlated with number of mixed plaques and grade of lumen stenosis in coronary arteries of patients with drug naïve T2DM. Conclusion: MMP9 may contribute to the initiation of atherosclerosis and may be a potential biomarker for the early identification of atherosclerosis in patients with diabetes. Clinical trial registration: https://clinicaltrials.gov, identifier NCT04424706.

Nicotine restores olfactory function by activation of prok2R/Akt/FoxO3a axis in Parkinson's disease.

BACKGROUND: Olfactory dysfunction occurs frequently in Parkinson's disease (PD). In this study, we aimed to explore the potential biomarkers and underlying molecular pathways of nicotine for the treatment of olfactory dysfunction in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. METHODS: MPTP was introduced into C57BL/6 male mice to generate a PD model. Regarding in vivo experiments, we performed behavioral tests to estimate the protective effects of nicotine in MPTP-induced PD mice. RNA sequencing and traditional molecular methods were used to identify molecules, pathways, and biological processes in the olfactory bulb of PD mouse models. Then, in vitro experiments were conducted to evaluate whether nicotine can activate the prok2R/Akt/FoxO3a signaling pathway in both HEK293T cell lines and primary olfactory neurons treated with 1-methyl-4-phenylpyridinium (MPP+). Next, prok2R overexpression (prok2R+) and knockdown (prok2R-) were introduced with lentivirus, and the Akt/FoxO3a signaling pathway was further explored. Finally, the damaging effects of MPP+ were evaluated in prok2R overexpression (prok2R+) HEK293T cell lines. RESULTS: Nicotine intervention significantly alleviated olfactory and motor dysfunctions in mice with PD. The prok2R/Akt/FoxO3a signaling pathway was activated after nicotine treatment. Consequently, apoptosis of olfactory sensory neurons was significantly reduced. Furthermore, prok2R+ and prok2R- HEK293T cell lines exhibited upregulation and downregulation of the Akt/FoxO3a signaling pathway, respectively. Additionally, prok2R+ HEK293T cells were resistant to MPP+-induced apoptosis. CONCLUSIONS: This study showed the effectiveness and underlying mechanisms of nicotine in improving hyposmia in PD mice. These improvements were correlated with reduced apoptosis of olfactory sensory neurons via activated prok2R/Akt/FoxO3a axis. These results explained the potential protective functions of nicotine in PD patients.

Deoxynivalenol Inhibits Progenitor Leydig Cell Development by Stimulating Mitochondrial Fission in Rats.

Deoxynivalenol (DON) is a common food contaminant that can impair male reproductive function. This study investigated the effects and mechanisms of DON exposure on progenitor Leydig cell (PLC) development in prepubertal male rats. Rats were orally administrated DON (0-4 mg/kg) from postnatal days 21-28. DON increased PLC proliferation but inhibited PLC maturation and function, including reducing testosterone levels and downregulating biomarkers like HSD11B1 and INSL3 at ≥2 mg/kg. DON also stimulated mitochondrial fission via upregulating DRP1 and FIS1 protein levels and increased oxidative stress by reducing antioxidant capacity (including NRF2, SOD1, SOD2, and CAT) in PLCs in vivo. In vitro, DON (2-4 µM) inhibited PLC androgen biosynthesis, increased reactive oxygen species production and protein levels of DRP1, FIS1, MFF, and pAMPK, decreased mitochondrial membrane potential and MFN1 protein levels, and caused mitochondrial fragmentation. The mitochondrial fission inhibitor mdivi-1 attenuated DON-induced impairments in PLCs. DON inhibited PLC steroidogenesis, increased oxidative stress, perturbed mitochondrial homeostasis, and impaired maturation. In conclusion, DON disrupts PLC development in prepubertal rats by stimulating mitochondrial fission.

A cubic DNA nanocage probe for in situ analysis of miRNA-10b in tumor-derived extracellular vesicles.

A cubic DNA nanocage probe is able to enter EVs derived from MDA-MB-231 cells and react with miRNA-10b. The probe-loaded EVs were employed to monitor the process of entry of miRNA-10b into MCF-10A cells, allowing visualization of EV-mediated intercellular communication of miRNA-10b between the cancer cells.

Metabolomic profiling reveals biomarkers for diverse flesh colors in jelly fungi (Auricularia cornea).

Auricularia cornea has garnered attention due to its nutrition, culinary applications, and promising commercial prospects. However, there is little information available regarding the metabolic profiling of various colors strains. In this study, 642 metabolites across 64 classes were identified by LC-MS/MS to understand the metabolic variations between white, pink and dark brown strains. Notably, prenol lipids, carboxylic acids and fatty acyls accounted for 46.8 % of the total. Comparative analysis revealed 17 shared differential metabolites (DMs) among them. ACP vs ACW exhibited 17 unique metabolites, including d-arginine and maleic acid, etc. ACP vs ACB showed 5 unique metabolites, with only PS(18:1(9Z)/0:0) demonstrating up-regulation. ACB vs ACW showed 8 unique metabolites, including 4-hydroxymandelic acid and 5'-methylthioadenosine, etc. KEGG enrichment analysis highlighted pathway variations, and MetPA analysis identified key-pathways influencing DMs accumulation in A. cornea. This pioneering metabolomics study offers insights into A. cornea metabolic profiling, potential applications, and guides further research.

Polydopamine functionalized dendritic fibrous silica nanoparticles as a generic platform for nucleic acid-based biosensing.

Accurate and rapid detection of nucleic acid sequences is of utmost importance in various fields, including disease monitoring, clinical treatment, gene analysis and drug discovery. In this study, we developed a "turn-on" fluorescence biosensor that enables simple and highly efficient detection of nucleic acid biomarkers. Our approach involves the utilization of 6-carboxyfluorescein modified single-stranded DNA (FAM-ssDNA) as molecular recognition element, along with polydopamine-functionalized dendritic fibrous nanosilica (DFNS). FAM-ssDNA serves as both specific molecular recognition element for the target analyte and reporter capable of transducing a detectable signal through Watson-Crick base pairing. The polydopamine-functionalized DFNS (DFNS@DA) exhibits strong binding to FAM-ssDNA via polyvalent metal mediated coordination leading to effective quenching by fluorescence resonance energy transfer. In the presence of a complementary target sequence, FAM-ssDNA forms hybridized structure and detaches from DFNS@DA, which causes an increased fluorescence emission. The analytical system based on FAM-ssDNA and DFNS@DA demonstrates exceptional sensitivity, selectivity, and rapid response for the detection of nucleic acid sequences, leveraging the high adsorption and quenching properties of DFNS@DA. For the first proof of concept, we demonstrated the successful detection of microRNA (miR-21) in cancer cells using the FAM-ssDNA/DFNS@DA system. Our results highlight the promising capabilities of DFNS@DA and nucleic acid-based biosensors, offering a generic and cost-effective solution for the detection of nucleic acid-related biomarkers.

Development of a self-reinforced starch-derived film with biocompatibility and mechanical properties.

The scraps produced while processing packaging materials will cause a waste of resources. In this study, starch-based self-reinforced film (SSRF) using thermoplastic starch (TPS, 45 wt%) and polypropylene (PP, 53 wt%) was developed. The effect of extrusion times (1-4 times) on the film structure and performance was explored. The results show as the number of extrusions increases, the color of SSRF deepens from gray-white to brown, and the crystallinity increases. The mechanical properties of the four types of SSRF first increase and then decrease. The 2-SSRF has the best performance, with tensile strength of 13.23 MPa, elongation at break of 61.35%, Young's modulus of 1128.99 MPa, and flexural strength of 33.19 MPa. Proper extrusion improves the compatibility of TPS and PP. However, repeated extrusion will cause PP degradation and TPS carbonization, reducing interfacial interaction. This study developed new starch-based self-reinforced film and provided theoretical guidance for reusing packaging material scraps.