Genotypic and Phenotypic Spectrum of maple syrup urine disease in Zhejiang of China.

BACKGROUND: Maple Syrup Urine Disease (MSUD) is an autosomal recessive metabolic disorder originating from defects in the branched-chain α-ketoacid dehydrogenase (BCKDH) complex encoded by BCKDHA, BCKDHB, and DBT. This condition presents a spectrum of symptoms and potentially fatal outcomes. Although numerous mutations in the BCKDH complex genes associated with MSUD have been identified, the relationship between specific genotypes remains to be fully elucidated. AIM: Our objective was to predict the pathogenicity of these genetic mutations and establish potential links between genotypic alterations and the clinical phenotypes of MSUD. DESIGN: Retrospective population-based cohort. METHODS: We analyzed 20 MSUD patients from the Children's Hospital at Zhejiang University School of Medicine (Hangzhou, China), recorded from January 2010 to May 2023. Patients' blood samples were collected by heel-stick through neonatal screening, and amino acid profiles were measured by tandem mass spectrometry. In silico methods were employed to assess the pathogenicity, stability, and biophysical properties. Various computation tools were utilized for assessment, namely PredictSNP, MAGPIE, iStable, Align GVGD, ConSurf and SNP effect. RESULTS: We detected 25 distinct mutations, including 12 novel mutations. The BCKDHB gene was the most commonly affected (53.3%) compared to the BCKDHA gene (20.0%) and DBT gene (26.7%). In silico webservers predicted all novel mutations were disease-causing. CONCLUSIONS: This study highlights the genetic complexity of MSUD and underscores the importance of early detection and intervention. Integrating neonatal screening with advanced sequencing methodologies is pivotal in ensuring precise diagnosis and effective management of MSUD, thereby significantly improving the prognosis for individuals afflicted with this condition.

Daphne genkwa: Ethnopharmacology, phytochemistry and pharmacology of an important traditional Chinese medicine.

Daphne genkwa, as a traditional medicine, is widely distributed in China, Korea and Vietnam. In China, the dried flower buds of this plant are named "Yuanhua". It has the ability to effectively promote urination, eliminate phlegm and alleviate cough, eliminate parasites and cure of scabies, with a broad spectrum of pharmacological effects and considerable clinical efficacy. This paper provides a summary and classification of the main chemical constituents of D. genkwa based on a review of relevant domestic and foreign literature. It also outlines the current research status of traditional clinical usage, pharmacological effects, and toxicity of D. genkwa. The aim is to provide a theoretical basis for further study of D. genkwa and its potential new clinical applications.

Ruthenium Nanoclusters and Single Atoms on α-MoC/N-Doped Carbon Achieves Low-Input/Input-Free Hydrogen Evolution via Decoupled/Coupled Hydrazine Oxidation.

The hydrazine oxidation-assisted H2 evolution method promises low-input and input-free hydrogen production. However, developing high-performance catalysts for hydrazine oxidation (HzOR) and hydrogen evolution (HER) is challenging. Here, we introduce a bifunctional electrocatalyst α-MoC/N-C/RuNSA, merging ruthenium (Ru) nanoclusters (NCs) and single atoms (SA) into cubic α-MoC nanoparticles-decorated N-doped carbon (α-MoC/N-C) nanowires, through electrodeposition. The composite showcases exceptional activity for both HzOR and HER, requiring -80 mV and -9 mV respectively to reach 10 mA cm-2. Theoretical and experimental insights confirm the importance of two Ru species for bifunctionality: NCs enhance the conductivity, and its coexistence with SA balances the H ad/desorption for HER and facilitates the initial dehydrogenation during the HzOR. In the overall hydrazine splitting (OHzS) system, α-MoC/N-C/RuNSA excels as both anode and cathode materials, achieving 10 mA cm-2 at just 64 mV. The zinc hydrazine (Zn-Hz) battery assembled with α-MoC/N-C/RuNSA cathode and Zn foil anode can exhibit 97.3 % energy efficiency, as well as temporary separation of hydrogen gas during the discharge process. Therefore, integrating Zn-Hz with OHzS system enables self-powered H2 evolution, even in hydrazine sewage. Overall, the amalgamation of NCs with SA achieves diverse catalytic activities for yielding multifold hydrogen gas through advanced cell-integrated-electrolyzer system.

Frequency-encoded eye tracking smart contact lens for human-machine interaction.

Eye tracking techniques enable high-efficient, natural, and effortless human-machine interaction by detecting users' eye movements and decoding their attention and intentions. Here, a miniature, imperceptible, and biocompatible smart contact lens is proposed for in situ eye tracking and wireless eye-machine interaction. Employing the frequency encoding strategy, the chip-free and battery-free lens successes in detecting eye movement and closure. Using a time-sequential eye tracking algorithm, the lens has a great angular accuracy of <0.5°, which is even less than the vision range of central fovea. Multiple eye-machine interaction applications, such as eye-drawing, Gluttonous Snake game, web interaction, pan-tilt-zoom camera control, and robot vehicle control, are demonstrated on the eye movement model and in vivo rabbit. Furthermore, comprehensive biocompatibility tests are implemented, demonstrating low cytotoxicity and low eye irritation. Thus, the contact lens is expected to enrich approaches of eye tracking techniques and promote the development of human-machine interaction technology.

A rapid multi-parametric quantitative MR imaging method to assess Parkinson's disease: a feasibility study.

BACKGROUND: MULTIPLEX is a single-scan three-dimensional multi-parametric MRI technique that provides 1 mm isotropic T1-, T2*-, proton density- and susceptibility-weighted images and the corresponding quantitative maps. This study aimed to investigate its feasibility of clinical application in Parkinson's disease (PD). METHODS: 27 PD patients and 23 healthy control (HC) were recruited and underwent a MULTIPLEX scanning. All image reconstruction and processing were automatically performed with in-house C + + programs on the Automatic Differentiation using Expression Template platform. According to the HybraPD atlas consisting of 12 human brain subcortical nuclei, the region-of-interest (ROI) based analysis was conducted to extract quantitative parameters, then identify PD-related abnormalities from the T1, T2* and proton density maps and quantitative susceptibility mapping (QSM), by comparing patients and HCs. RESULTS: The ROI-based analysis revealed significantly decreased mean T1 values in substantia nigra pars compacta and habenular nuclei, mean T2* value in subthalamic nucleus and increased mean QSM value in subthalamic nucleus in PD patients, compared to HCs (all p values < 0.05 after FDR correction). The receiver operating characteristic analysis showed all these four quantitative parameters significantly contributed to PD diagnosis (all p values < 0.01 after FDR correction). Furthermore, the two quantitative parameters in subthalamic nucleus showed hemicerebral differences in regard to the clinically dominant side among PD patients. CONCLUSIONS: MULTIPLEX might be feasible for clinical application to assist in PD diagnosis and provide possible pathological information of PD patients' subcortical nucleus and dopaminergic midbrain regions.

Motor symptoms of Parkinson's disease are affected by temperature: A controlled pilot study.

PURPOSE: The motor symptoms (MS) of Parkinson's disease (PD) have been affecting the quality of life in patients. In clinical practice, most patients with PD report that MS are more severe in winter than in summer, and hyperthermic baths (HTB) could temporarily improve MS. The study aimed to evaluate the effects of seasonal variation and aquatic thermal environment of HTB on the MS of PD. PATIENTS AND METHODS: A cross-sectional study of 203 Chinese Han patients was performed. Univariate and multivariate analyses were performed to analyze seasonal variation in MS relative to baseline data (sex, age at onset, duration, season of birth, Hoehn and Yahr stage, family history, levodopa equivalent dose, and the effect of HTB on MS). Ten subjects participated in the HTB study, and one patient dropped out. The paired Wilcoxon rank test was used to assess the differences in the Movement Disorder Society-United Parkinson's disease Rating Scale (MDS-UPDRS) part III motor examination total scores and the modified Webster Symptoms Score between non-HTB and before HTB and between non-HTB and after HTB. RESULTS: The improvement of MS after HTB was an independent risk factor for seasonal variation in MS (OR, 25.203; 95% CI, 10.951-58.006; p = .000). Patients with PD had significant improvements in the MDS-UPDRS part III motor examination total scores, especially in bradykinesia (p = .043), rigidity (p = .008), posture (p = .038), and rest tremor amplitude (p = .047). CONCLUSION: Seasonal variation in temperature and water temperature of HTB may affect MS in some patients with PD. Simple HTB could be recommended as physiotherapy for patients with PD who report temperature-sensitive MS.

Identification of a highly conserved neutralizing epitope within the RBD region of diverse SARS-CoV-2 variants.

The constant emergence of SARS-CoV-2 variants continues to impair the efficacy of existing neutralizing antibodies, especially XBB.1.5 and EG.5, which showed exceptional immune evasion properties. Here, we identify a highly conserved neutralizing epitope targeted by a broad-spectrum neutralizing antibody BA7535, which demonstrates high neutralization potency against not only previous variants, such as Alpha, Beta, Gamma, Delta and Omicron BA.1-BA.5, but also more recently emerged Omicron subvariants, including BF.7, CH.1.1, XBB.1, XBB.1.5, XBB.1.9.1, EG.5. Structural analysis of the Omicron Spike trimer with BA7535-Fab using cryo-EM indicates that BA7535 recognizes a highly conserved cryptic receptor-binding domain (RBD) epitope, avoiding most of the mutational hot spots in RBD. Furthermore, structural simulation based on the interaction of BA7535-Fab/RBD complexes dissects the broadly neutralizing effect of BA7535 against latest variants. Therapeutic and prophylactic treatment with BA7535 alone or in combination with BA7208 protected female mice from the circulating Omicron BA.5 and XBB.1 variant infection, suggesting the highly conserved neutralizing epitope serves as a potential target for developing highly potent therapeutic antibodies and vaccines.

Evolution of the gene regulatory network of body axis by enhancer hijacking in amphioxus.

A central goal of evolutionary developmental biology is to decipher the evolutionary pattern of gene regulatory networks (GRNs) that control embryonic development, and the mechanism underlying GRNs evolution. The Nodal signaling that governs the body axes of deuterostomes exhibits a conserved GRN orchestrated principally by Nodal, Gdf1/3, and Lefty. Here we show that this GRN has been rewired in cephalochordate amphioxus. We found that while the amphioxus Gdf1/3 ortholog exhibited nearly no embryonic expression, its duplicate Gdf1/3-like, linked to Lefty, was zygotically expressed in a similar pattern as Lefty. Consistent with this, while Gdf1/3-like mutants showed defects in axial development, Gdf1/3 mutants did not. Further transgenic analyses showed that the intergenic region between Gdf1/3-like and Lefty could drive reporter gene expression as that of the two genes. These results indicated that Gdf1/3-like has taken over the axial development role of Gdf1/3 in amphioxus, possibly through hijacking Lefty enhancers. We finally demonstrated that, to compensate for the loss of maternal Gdf1/3 expression, Nodal has become an indispensable maternal factor in amphioxus and its maternal mutants caused axial defects as Gdf1/3-like mutants. We therefore demonstrated a case that the evolution of GRNs could be triggered by enhancer hijacking events. This pivotal event has allowed the emergence of a new GRN in extant amphioxus, presumably through a stepwise process. In addition, the co-expression of Gdf1/3-like and Lefty achieved by a shared regulatory region may have provided robustness during body axis formation, which provides a selection-based hypothesis for the phenomena called developmental system drift.

An ultra-sensitive platinized nanocavity electrode for analysis of cytosolic catecholamines in one living cell.

The catecholamines, mainly dopamine (DA), are present in the cellular cytosol with low abundance, while, play key roles in various neurodegenerative disorders. Here, platinized nanocavity carbon electrodes are employed to analyze cytosolic catecholamines in a single living PC12 cell, which is not easily quantified using the classic electrodes. The confined structure and excellent conductivity in the platinized nanocavity accelerate the electron transfer of the DA, resulting in a low detection limit down to 50 nM. The sensitivity of DA detection is improved to be 10.73 pA mM-1 nm-1 in the response range of 50 nM-100 µM, which guarantees quantitative analysis of cytosolic catecholamines with low abundance. Eventually, the platinized nanocavity electrode is employed to detect cytosolic catecholamines in a single PC12 cell without an obvious interruption of cellular catecholamine level. The cytosolic catecholamines in a single PC12 cell is measured in situ to be 0.1 µM, which is achieved for the first time at the single cell level using the electrochemical method. The results demonstrate that the nanocavity electrode with a high sensitivity could offer a promising means to dynamically track catecholamines in a single cell.

Identification of heel bone mineral density as a risk factor of Alzheimer's disease by analyzing large-scale genome-wide association studies datasets.

Introduction: Both low bone mineral density (BMD) and Alzheimer's disease (AD) commonly co_occur in the older adult. Until now, the association between AD and BMD has been widely reported by observational studies. However, Mendelian randomization (MR) studies did not support the causal association between BMD and AD. We think that the lack of significant causal association between AD and BMD identified by recent MR studies may be caused by small number of potential instrumental variables. Methods: We conduct a MR study to evaluate the causal effect of heel BMD on the risk of AD using 1,362 genome-wide significant and independent (p < 5.00E-08) heel BMD genetic variants as the potential instrumental variables, which are identified by a large-scale genome wide association study (GWAS) of heel BMD in 394,929 UK Biobank individuals. Using these 1,362 genome-wide significant and independent heel BMD genetic variants, we extracted their corresponding AD GWAS summary results in IGAP AD GWAS dataset (n = 63,926) and FinnGen AD GWAS dataset (n = 377,277). Five methods including inverse-variance weighted meta-analysis (IVW), weighted median, MR-Egger, MR-PRESSO, and MRlap were selected to perform the MR analysis. 951 of these 1,362 genetic variants are available in AD GWAS dataset. Results: We observed statistically significant causal effect of heel BMD on the risk of AD using IVW in IGAP AD GWAS dataset (OR = 1.048, 95%CI: 1.002-1.095, p = 0.04) and FinnGen AD GWAS dataset (OR = 1.053, 95% CI:1.011-1.098, p = 0.011). Importantly, meta-analysis of IVW estimates from IGAP and FinnGen further supported the causal effect of heel BMD on the risk of AD (OR = 1.051, 95% CI: 1.02-1.083, p = 0.0013). Discussion: Collectively, our current MR study supports heel BMD to be a risk factor of AD by analyzing the large-scale heel BMD and AD GWAS datasets. The potential mechanisms underlying the association between heel BMD and AD should be further evaluated in future.

Amorphization-Induced Cation Exchange in Indium Oxide Nanosheets for CO2-to-Ethanol Conversion.

Cation exchange (CE) in metal oxides under mild conditions remains an imperative yet challenging goal to tailor their composition and enable practical applications. Herein, we first develop an amorphization-induced strategy to achieve room-temperature CE for universally synthesizing single-atom doped In2O3 nanosheets (NSs). Density functional theory (DFT) calculations elucidate that the abundant coordination-unsaturated sites present in a-In2O3 NSs are instrumental in surmounting the energy barriers of CE reactions. Empirically, a-In2O3 NSs as the host materials successfully undergo exchange with unary cations (Cu2+, Co2+, Mn2+, Ni2+), binary cations (Co2+Mn2+, Co2+Ni2+, Mn2+Ni2+), and ternary cations (Co2+Mn2+Ni2+). Impressively, high-loading single-atom doped (over 10 atom %) In2O3 NSs were obtained. Additionally, Cu/a-In2O3 NSs exhibit an excellent ethanol yield (798.7 µmol g-1 h-1) with a high selectivity of 99.5% for the CO2 photoreduction. This work offers a new approach to induce CE reactions in metal oxides under mild conditions and constructs scalable single-atom doped catalysts for critical applications.

Click-Chemistry-Enabled Nanopipettes for the Capture and Dynamic Analysis of a Single Mitochondrion inside One Living Cell.

The in-depth study of single cells requires the dynamically molecular information in one particular nanometer-sized organelle in a living cell, which is difficult to achieve using current methods. Due to high efficiency of click chemistry, a new nanoelectrode-based pipette architecture with dibenzocyclooctyne at the tip is designed to realize fast conjugation with azide group-containing triphenylphosphine, which targets mitochondrial membranes. The covalent binding of one mitochondrion at the tip of the nanopipette allows a small region of the membrane to be isolated on the Pt surface inside the nanopipette. Therefore, the release of reactive oxygen species (ROS) from the mitochondrion is monitored, which is not interfered by the species present in the cytosol. The dynamic tracking of ROS release from one mitochondrion reveals the distinctive "ROS-induced ROS release" within the mitochondria. Further study of RSL3-induced ferroptosis using nanopipettes provides direct evidence for supporting the noninvolvement of glutathione peroxidase 4 in the mitochondria during RSL3-induced ROS generation, which has not previously been observed at the single-mitochondrion level. Eventually, this established strategy should overcome the existing challenge of the dynamic measurement of one special organelle in the complicated intracellular environment, which opens a new direction for electroanalysis in subcellular analysis.

Magnolol as STAT3 inhibitor for treating multiple sclerosis by restricting Th17 cells.

OBJECTIVE: Multiple sclerosis (MS) is an immune disease in the central nervous system (CNS) associated with Th17 cells. Moreover, STAT3 initiates Th17 cell differentiation and IL-17A expression through facilitating RORγt in MS. Here, we reported that magnolol, isolated from Magnolia officinalis Rehd. Et Wils, was regarded as a candidate for MS treatment verified by both in vitro and in vivo studies. METHODS: In vivo, experimental autoimmune encephalomyelitis (EAE) model in mice was employed to evaluate the alleviation of magnolol on myeloencephalitis. In vitro, FACS assay was employed to evaluate the effect of magnolol on Th17 and Treg cell differentiation and IL-17A expression; network pharmacology-based study was applied to probe the involved mechanisms; western blotting, immunocytochemistry, and luciferase reporter assay was used to further confirm the regulation of magnolol on JAK/STATs signaling pathway; surface plasmon resonance (SPR) assay and molecular docking were applied to manifest affinity with STAT3 and binding sites; overexpression of STAT3 was employed to verify whether magnolol attenuates IL-17A through STAT3 signaling pathway. RESULTS: In vivo, magnolol alleviated loss of body weight and severity of EAE mice; magnolol improved lesions in spinal cords and attenuated CD45 infiltration, and serum cytokines levels; correspondingly, magnolol focused on inhibiting Th17 differentiation and IL-17A expression in splenocyte of EAE mice; moreover, magnolol selectively inhibited p-STAT3(Y705) and p-STAT4(Y693) of both CD4+ and CD8+ T cells in splenocyte of EAE mice. In vitro, magnolol selectively inhibited Th17 differentiation and IL-17A expression without impact on Treg cells; network pharmacology-based study revealed that magnolol perhaps diminished Th17 cell differentiation through regulating STAT family members; western blotting further confirmed that magnolol inhibited p-JAK2(Y1007) and selectively antagonized p-STAT3(Y705) and slightly decreased p-STAT4(Y693); magnolol antagonized both STAT3 nucleus location and transcription activity; magnolol had a high affinity with STAT3 and the specific binding site perhaps to be at SH2 domain; overexpression of STAT3 resulted in failed inhibition of magnolol on IL-17A. CONCLUSION: Magnolol selectively inhibited Th17 differentiation and cytokine expression through selectively blocking of STAT3 resulting in decreased the ratio of Th17/Treg cells for treating MS, suggesting that the potential of magnolol for treating MS as novel STAT3 inhibitor.

In Situ Spatial Analysis of Metabolic Heterogeneity in Single Living Tumor Spheroids Using Nanocapillary-Based Electrospray Ionization Mass Spectroscopy.

Spatial metabolomic analysis of individual tumor spheroids can help investigate metabolic rearrangements in different cellular regions of a spheroid. In this work, a nanocapillary-based electrospray ionization mass spectroscopy (ESI-MS) method is established that could realize the spatial sampling of cellular components in different regions of a single living tumor spheroid and the subsequent MS analysis for a metabolic study. During the penetration of the nanocapillary into the spheroid for sampling, this "wound surface" at the outer layer of the spheroid takes only 0.1% of the whole area that maximally maintains the cellular activity inside the spheroid for the metabolic analysis. Using the ESI-MS analysis, different metabolic activities in the inner and outer (upper and lower) layers of a single spheroid are revealed, giving a full investigation of the metabolic heterogeneity inside one living tumor spheroid for the first time. In addition, the metabolic activities between the outer layer of the spheroid and two-dimensional (2D)-cultured cells show obvious differences, which suggests more frequent cell-cell and cell-extracellular environment interactions during the culture of the spheroid. This observation not only establishes a powerful tool for the in situ spatial analysis of the metabolic heterogeneity in single living tumor spheroids but also provides molecular information to elucidate the metabolic heterogeneity in this three-dimensional (3D)-cultured cell model.

MicroRNA-146a Promotes Embryonic Stem Cell Differentiation towards Vascular Smooth Muscle Cells through Regulation of Kruppel-like Factor 4.

OBJECTIVE: Vascular smooth muscle cell (VSMC) differentiation from stem cells is one source of the increasing number of VSMCs that are involved in vascular remodeling-related diseases such as hypertension, atherosclerosis, and restenosis. MicroRNA-146a (miR-146a) has been proven to be involved in cell proliferation, migration, and tumor metabolism. However, little is known about the functional role of miR-146a in VSMC differentiation from embryonic stem cells (ESCs). This study aimed to determine the role of miR-146a in VSMC differentiation from ESCs. METHODS: Mouse ESCs were differentiated into VSMCs, and the cell extracts were analyzed by Western blotting and RT-qPCR. In addition, luciferase reporter assays using ESCs transfected with miR-146a/mimic and plasmids were performed. Finally, C57BL/6J female mice were injected with mimic or miR-146a-overexpressing ESCs, and immunohistochemistry, Western blotting, and RT-qPCR assays were carried out on tissue samples from these mice. RESULTS: miR-146a was significantly upregulated during VSMC differentiation, accompanied with the VSMC-specific marker genes smooth muscle-alpha-actin (SMαA), smooth muscle 22 (SM22), smooth muscle myosin heavy chain (SMMHC), and h1-calponin. Furthermore, overexpression of miR-146a enhanced the differentiation process in vitro and in vivo. Concurrently, the expression of Kruppel-like factor 4 (KLF4), predicted as one of the top targets of miR-146a, was sharply decreased in miR-146a-overexpressing ESCs. Importantly, inhibiting KLF4 expression enhanced the VSMC-specific gene expression induced by miR-146a overexpression in differentiating ESCs. In addition, miR-146a upregulated the mRNA expression levels and transcriptional activity of VSMC differentiation-related transcription factors, including serum response factor (SRF) and myocyte enhancer factor 2c (MEF-2c). CONCLUSION: Our data support that miR-146a promotes ESC-VSMC differentiation through regulating KLF4 and modulating the transcription factor activity of VSMCs.

Dysregulation of Circulatory Levels of lncRNAs in Parkinson's Disease.

Emerging evidence suggested that long non-coding RNAs (lncRNAs) were involved in Parkinson's disease (PD) pathogenesis. Herein, we used gene expression profiles from GEO database to construct a PD-specific ceRNA network. Functional enrichment analysis suggested that ceRNA network might participate in the development of PD. PPI networks were constructed, and the ceRNA subnetwork based on five hub genes was set up. In a cohort of 32 PD patients and 31 healthy controls, the expression of 10 DElncRNAs (TTC3-AS1, LINC01259, ZMYND10-AS1, CHRM3-AS1, MYO16-AS1, AGBL5-IT1, HOTAIRM1, RABGAP1L-IT1, HLCS-IT1, and LINC00393) were further verified. Consistent with the microarray data, LINC01259 expression was significantly lower in PD patients compared with controls (P = 0.008). Intriguingly, such a difference was only observed among male patients and male controls when dividing study participants based on their gender (P = 0.016). However, the expression of other lncRNAs did not differ significantly between the two groups. Receiver operating characteristic (ROC) curve analysis revealed that the diagnostic power of LINC01259 was 0.694 for PD and 0.677 for early-stage PD. GSEA enrichment analysis revealed that LINC01259 was mainly enriched in biological processes associated with immune function and inflammatory response. Moreover, LINC01259 expression was not correlated with age of patients, disease duration, disease stage, MDS-UPDRS score, MDS-UPDRS III score, MMSE score, and MOCA score. The current study provides further evidence for the dysregulation of lncRNAs in circulating leukocytes of PD patients, revealing that LINC01259 has clinical potential as a novel immune and inflammatory biomarker for PD and early-stage PD diagnosis.

Ultralong Lifetime of Plasmon-Excited Electrons Realized in Nonepitaxial/Epitaxial Au@CdS/CsPbBr3 Triple-Heteronanocrystals.

Combination of the strong light-absorbing power of plasmonic metals with the superior charge carrier dynamics of halide perovskites is appealing for bio-inspired solar-energy conversion due to the potential to acquire long-lived plasmon-induced hot electrons. However, the direct coupling of these two materials, with Au/CsPbBr3 heteronanocrystals (HNCs) as a prototype, results in severe suppression of plasmon resonances. The present work shows that interfacial engineering is a key knob for overcoming this impediment, based on the creation of a CdS mediate layer between Au and CsPbBr3 forming atomically organized Au-CdS and CdS-CsPbBr3 interfaces by nonepitaxial/epitaxial combined strategy. Transient spectroscopy studies demonstrate that the resulting Au@CdS/CsPbBr3 HNCs generate remarkably long-lived plasmon-induced charge carriers with lifetime up to nanosecond timescale, which is several orders of magnitude longer than those reported for colloidal plasmonic metal-semiconductor systems. Such long-lived carriers extracted from plasmonic antennas enable to drive CO2 photoreduction with efficiency outperforming previously reported CsPbBr3 -based photocatalysts. The findings disclose a new paradigm for achieving much elongated time windows to harness the substantial energy of transient plasmons through realization of synergistic coupling of plasmonic metals and halide perovskites.

Electrochemical Molecule Trap-Based Sensing of Low-Abundance Enzymes in One Living Cell.

Measuring the activity of low-abundance enzymes, down to a few molecules in one living cell, is important but challenging to elucidate their biological function. Here, an electrochemical molecule trap is established at the tip of a nanopipette with an electrochemical detector, in which the diffusion of the molecules away from the electrochemical detector is prevented by electro-osmotic flow (EOF). Accordingly, a limited amount of enzymes is trapped to continuously catalyze the conversion of the substrate to generate a sufficient amount of the byproduct hydrogen peroxide for electrochemical measurements. The resistive pulse sensing of the enzymes in single liposomes validates the detection sensitivity down to 15 molecules. Using this ultrasensitive electrochemical strategy, the activity of 60 sphingomyelinase molecules inside single unstimulated living J774 cells is measured, which was hardly detected by previous methods. The established electrochemical molecule trap-based sensing approach opens the door toward single-molecule electrochemical detection in one living cell. This success will solve the long-standing problem regarding the study of the activity of low-abundance proteins in cells in their native physiological state and greatly enhance the understanding of the roles of proteins in cellular behavior.

Spatial Analysis of Reactive Oxygen Species in a 3D Cell Model Using a Sensitive Nanocavity Electrode.

The analysis of biomolecules in a 3D cell model is crucial for the collection of spatial information close to the actual organ. In this work, a highly sensitive platinized open carbon nanocavity electrode is fabricated to investigate reactive oxygen species (ROS) in three regions (proliferating zone, quiescent zone, and necrotic core) of a 3D CT26 cell model. The presence of a nanocavity permits more frequent collisions of ROS on the Pt surface, accelerating electron transfer, and thus pushes the detection limit down to 1 nM. This improved detection sensitivity guarantees the spatial investigation of the ROS distribution in a 3D cell sphere, including a high concentration in the outer proliferating layer even without any external stimulus, a low concentration in the quiescent layer, and almost no ROS at the center. The observation of ROS in the cell sphere without the stimulus reveals the presence of oxygen stress in the 3D cancer cell model, which is obviously different from the previous observation in living cultured 2D cells. This discovery provides direct evidence about the discrepancy about the metabolism in 2D and 3D cells, which could also direct a new study in cell electroanalysis to achieve more actual molecular information in life study.

Glucose to Platelet Ratio: A Potential Predictor of Hemorrhagic Transformation in Patients with Acute Ischemic Stroke.

Glucose and platelet are two easily obtained clinical indicators; the present research aimed to demonstrate their association with hemorrhagic transformation (HT) in acute ischemic stroke (AIS) patients without thrombolytic or thrombectomy therapy. This was a single-center retrospective study. Patients who were diagnosed with HT after AIS were included in the HT group. Meanwhile, using the propensity score matching (PSM) approach, with a ratio of 1:2, matched patients without HT were included in the non-HT group. Serum G/P levels were measured on the first morning after admission (at least eight hours after the last meal). Characteristics were compared between the two groups. Multivariate logistic regression was used to determine the independent relationship between G/P and HT after AIS, with G/P being divided into quartiles. From January 2013 to March 2022, we consecutively included 643 AIS patients with HT (426/643 [66.25%] with HI and 217/643 [33.75%] with PH), and 1282 AIS patients without HT, at the First Affiliated Hospital of Wenzhou Medical University. The HT group had higher G/P levels than the non-HT group (0.04 ± 0.02 vs. 0.03 ± 0.02, p < 0.001). However, there was no difference in G/P levels between HI and PH subgroups (0.04 ± 0.02 vs. 0.04 ± 0.02, p > 0.05). Moreover, the G/P levels were divided into quartiles (Q1 ≤ 0.022; Q2 = 0.023−0.028; Q3 = 0.029−0.039; Q4 ≥ 0.040), with Q1 being settled as the reference layer. After controlling the confounders, multivariate regression analyses showed that the Q4 layer (Q4: G/P ≥ 0.040) was independently associated with elevated HT risk (odds ratio [OR] = 1.85, 95% CI = 1.31−2.63, p < 0.001). G/P levels on admission were independently associated with HT risk in AIS patients. In clinical practice, adequate attention should be paid to AIS patients with elevated G/P levels (G/P ≥ 0.040).