Early Conversion of Intensive Insulin Therapy to IDegLira Demonstrates Higher Efficacy and Safety in Reducing Fasting Blood Glucose and HbA1c in T2DM Patients.

Background: A short-term insulin intensive therapy is an important method used in clinical practice to control blood glucose, and a scientific post-treatment plan is key to long-term blood glucose stability control. This study aimed to investigate efficacy and safety of early conversion of intensive insulin therapy to IDegLira in T2DM patients. Methods: This study was a prospective study, involving 80 T2DM patients finally. Patients were firstly treated with insulin for intensified therapy (Pre-IDegLira group), then switched to insulin degludec and liraglutide (IDegLira) for 3 months (IDegLira-3 months group). Data including HbA1c, fasting blood glucose, fasting C-peptide, weight, insulin dosage, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were analyzed. Correlations between fasting blood glucose and other parameters were evaluated with Pearson correlation analysis. Results: IDegLira early conversion significantly reduced fasting blood glucose (p<0.001), weight (p=0.015), and insulin dosage (p=0.001) of T2DM patients compared to those of Pre-IDegLira group. HbA1c level was remarkably lower in T2DM patients underwent IDegLira early conversion compared to that in Pre-IDegLira group (p<0.001), with HbA1c <7% proportion of 73.75% (59/80). IDegLira early conversion significantly downregulated levels of TC (p<0.001), TG (p<0.001), LDL-C (p<0.001), and upregulated HDL-C level (p=0.017) of T2DM patients, compared to those in Pre-IDegLira group. IDegLira early conversion markedly reduced ALT (p<0.001) and AST (p=0.002) levels of T2DM patients compared to those in Pre-IDegLira group. IDegLira early conversion demonstrated a positive correlation between fasting blood glucose and HbA1c (r=0.531, p<0.001) or TG level (r=0.336, p=0.002) in T2DM patients. Conclusion: Early conversion of intensive insulin therapy to IDegLira effectively reduced fasting blood glucose and HbA1c in T2DM patients with higher safety.

Cavity Floquet engineering.

Floquet engineering is a promising tool to manipulate quantum systems coherently. A well-known example is the optical Stark effect, which has been used for optical trapping of atoms and breaking time-reversal symmetry in solids. However, as a coherent nonlinear optical effect, Floquet engineering typically requires high field intensities obtained in ultrafast pulses, severely limiting its use. Here, we demonstrate using cavity engineering of the vacuum modes to achieve orders-of-magnitude enhancement of the effective Floquet field, enabling Floquet effects at an extremely low fluence of 450 photons/µm2. At higher fluences, the cavity-enhanced Floquet effects lead to 50 meV spin and valley splitting of WSe2 excitons, corresponding to an enormous time-reversal breaking, non-Maxwellian magnetic field of over 200 T. Utilizing such an optically controlled effective magnetic field, we demonstrate an ultrafast, picojoule chirality XOR gate. These results suggest that cavity-enhanced Floquet engineering may enable the creation of steady-state or quasi-equilibrium Floquet bands, strongly non-perturbative modifications of materials beyond the reach of other means, and application of Floquet engineering to a wide range of materials and applications.

Carrier-phonon decoupling in perovskite thermoelectrics via entropy engineering.

Thermoelectrics converting heat and electricity directly attract broad attentions. To enhance the thermoelectric figure of merit, zT, one of the key points is to decouple the carrier-phonon transport. Here, we propose an entropy engineering strategy to realize the carrier-phonon decoupling in the typical SrTiO3-based perovskite thermoelectrics. By high-entropy design, the lattice thermal conductivity could be reduced nearly to the amorphous limit, 1.25 W m-1 K-1. Simultaneously, entropy engineering can tune the Ti displacement, improving the weighted mobility to 65 cm2 V-1 s-1. Such carrier-phonon decoupling behaviors enable the greatly enhanced µW/κL of ~5.2 × 103 cm3 K J-1 V-1. The measured maximum zT of 0.24 at 488 K and the estimated zT of ~0.8 at 1173 K in (Sr0.2Ba0.2Ca0.2Pb0.2La0.2)TiO3 film are among the best of n-type thermoelectric oxides. These results reveal that the entropy engineering may be a promising strategy to decouple the carrier-phonon transport and achieve higher zT in thermoelectrics.

ECCT: Efficient Contrastive Clustering via Pseudo-Siamese Vision Transformer and Multi-view Augmentation.

Image clustering aims to divide a set of unlabeled images into multiple clusters. Recently, clustering methods based on contrastive learning have attracted much attention due to their ability to learn discriminative feature representations. Nevertheless, existing clustering algorithms face challenges in capturing global information and preserving semantic continuity. Additionally, these methods often exhibit relatively singular feature distributions, limiting the full potential of contrastive learning in clustering. These problems can have a negative impact on the performance of image clustering. To address the above problems, we propose a deep clustering framework termed Efficient Contrastive Clustering via Pseudo-Siamese Vision Transformer and Multi-view Augmentation (ECCT). The core idea is to introduce Vision Transformer (ViT) to provide the global view, and improve it with Hilbert Patch Embedding (HPE) module to construct a new ViT branch. Finally, we fuse the features extracted from the two ViT branches to obtain both global view and semantic coherence. In addition, we employ multi-view random aggressive augmentation to broaden the feature distribution, enabling the model to learn more comprehensive and richer contrastive features. Our results on five datasets demonstrate that ECCT outperforms previous clustering methods. In particular, the ARI metric of ECCT on the STL-10 (ImageNet-Dogs) dataset is 0.852 (0.424), which is 10.3% (4.8%) higher than the best baseline.

Structural basis of Frizzled 4 in recognition of Dishevelled 2 unveils mechanism of WNT signaling activation.

WNT signaling is fundamental in development and homeostasis, but how the Frizzled receptors (FZDs) propagate signaling remains enigmatic. Here, we present the cryo-EM structure of FZD4 engaged with the DEP domain of Dishevelled 2 (DVL2), a key WNT transducer. We uncover a distinct binding mode where the DEP finger-loop inserts into the FZD4 cavity to form a hydrophobic interface. FZD4 intracellular loop 2 (ICL2) additionally anchors the complex through polar contacts. Mutagenesis validates the structural observations. The DEP interface is highly conserved in FZDs, indicating a universal mechanism by which FZDs engage with DVLs. We further reveal that DEP mimics G-protein/ß-arrestin/GRK to recognize an active conformation of receptor, expanding current GPCR engagement models. Finally, we identify a distinct FZD4 dimerization interface. Our findings delineate the molecular determinants governing FZD/DVL assembly and propagation of WNT signaling, providing long-sought answers underlying WNT signal transduction.

Leptin protects chondrocytes by inhibiting autophagy via phosphoinositide 3 kinase/protein kinase B/mammalian target of rapamycin signaling pathway.

Leptin has been widely studied and found to have a significant impact on the development of osteoarthritis (OA). However, there are conflicting findings regarding the impact of leptin on chondrocytes. The study aimed to examine the impact of leptin on human chondrocytes and rats with OA. In the in vitro experiment, cartilage tissue obtained from patients hospitalized for knee replacement due to OA was collected for primary culture of chondrocytes. The proliferation and apoptosis of chondrocytes were assessed using cell counting kit-8 and flow cytometry. Autophagy levels were evaluated through monodansylcadaverine staining, mRFP-GFP-LC3 fluorescence, and transmission electron microscopy. Additionally, the expression of autophagy-related genes and proteins was analyzed using qRT-PCR and western blotting. In the in vivo experiment, an OA rat model was established. Following treatment with leptin and leptin antagonists, the cartilage tissues were examined using histology analysis (hematoxylin-eosin and Safranin O/fast green staining) and immunohistochemical. Mankin's score was utilized to assess the severity of OA, while qRT-PCR and western blotting were employed to detect the expression of autophagy-related genes and proteins in the cartilage. The ability of leptin to protect chondrocytes is achieved through the inhibition of autophagy via phosphoinositide 3 kinase/protein kinase B/mammalian target of rapamycin signaling pathway.

Small RNA GadY in Escherichia coli enhances conjugation system of IncP-1 by targeting SdiA.

Plasmid-mediated conjugation is a common mechanism for most bacteria to transfer antibiotic resistance genes (ARGs). The conjugative transfer of ARGs is emerging as a major threat to human beings. Although several transfer-related factors are known to regulate this process, small RNAs (sRNAs)-based regulatory roles remain to be clarified. Here, the Hfq-binding sRNA GadY in donor strain Escherichia coli (E. coli) SM10λπ was identified as a new regulator for bacterial conjugation. Two conjugation models established in our previous studies were used, which SM10λπ carrying a chromosomally integrated IncP-1α plasmid RP4 and a mobilizable plasmid pUCP24T served as donor cells, and P. aeruginosa PAO1 or E. coli EC600 as the recipients. GadY was found to promote SM10λπ-PAO1 conjugation by base-pairing with its target mRNA SdiA, an orphan LuxR-type receptor that responds to exogenous N-acylated homoserine lactones (AHLs). However, SM10λπ-EC600 conjugation was not affected due to EC600 lacking AHLs synthase. It indicates that the effects of GadY on conjugation depended on AHLs-SdiA signalling. Further study found GadY bound SdiA to negatively regulate the global RP4 repressors KorA and KorB. When under ciprofloxacin or levofloxacin treatment, GadY expression in donor strain was enhanced, and it positively regulated quinolone-induced SM10λπ-PAO1 conjugation. Thus, our study provides a novel role for sRNA GadY in regulating plasmid-mediated conjugation, which helps us better understand bacterial conjugation to counter antibiotic resistance.

High-Performance Sheet-Type Sulfide All-Solid-State Batteries Enabled by Dual-Function Li4.4Si Alloy-Modified Nano Silicon Anodes.

The silicon-based anodes are one of the promising anodes to achieve the high energy density of all-solid-state batteries (ASSBs). Nano silicon (nSi) is considered as a suitable anode material for assembling sheet-type sulfide ASSBs using thin free-standing Li6PS5Cl (LPSC) membrane without causing short circuit. However, nSi anodes face a significant challenge in terms of rapid capacity degradation during cycling. To address this issue, dual-function Li4.4Si modified nSi anode sheets are developed, in which Li4.4Si serves a dual role by not only providing additional Li+ but also stabilizing the anode structure with its low Young's modulus upon cycling. Sheet-type ASSBs equipped with the Li4.4Si modified nSi anode, thin LPSC membrane, and LiNi0.83Co0.11Mn0.06O2 (NCM811) cathode demonstrate exceptional cycle stability, with a capacity retention of 96.16% at 0.5 C (1.18 mA cm-2) after 100 cycles and maintain stability for 400 cycles. Furthermore, a remarkable cell-level energy density of 303.9 Wh kg-1 is achieved at a high loading of 5.22 mAh cm-2, representing a leading level of sulfide ASSBs using electrolyte membranes at room temperature. Consequently, the chemically stable slurry process implemented in the fabrication of Li4.4Si-modified nSi anode sheet paves the way for scalable applications of high-performance sulfide ASSBs.

Leidenfrost Effect-Induced Chaotic Vortex Flow for Efficient Mixing of Highly Viscous Droplets.

Efficiently mixing highly viscous liquids in microfluidic systems is appealing for green chemistry such as chemical synthesis and catalysis, but it is a long-standing challenge owing to the unfavorable diffusion kinetics. In this work, a new strategy is explored for mixing viscous droplets by harnessing a peculiar Leidenfrost state, where the substrate temperature is above the boiling point of the liquid without apparent liquid evaporation. Compared to the control experiment where the droplet stays at a similar temperature but in the contact boiling regime, the mixing time can be reduced significantly. Moreover, it is demonstrated that the liquid mixing originates from the chaotic convection flow in the Leidenfrost droplet, characterized by the internal vortex motion evidenced by the microscale visualization. A correlation between mixing time and droplet volume is also proposed, showing a good agreement with experimental results. It is further shown that Leidenfrost droplets can be used to synthesize nanoparticles of the desired morphology, and it is anticipated that this simple and scalable fabrication approach will find applications in the biological, pharmaceutical, and chemical industries.

Mechanistic Interrogation on Wound Healing and Scar Removing by the Mo4/3B2-x Nanoscaffold Revealed Regulated Amino Acid and Purine Metabolism.

Wound rehabilitation is invariably time-consuming, scar formation further weakens therapeutic efficacy, and detailed mechanisms at the molecular level remain unclear. In this work, a Mo4/3B2-x nanoscaffold was fabricated and utilized for wound healing and scar removing in a mice model, while metabolomics was used to study the metabolic reprogramming of metabolome during therapy at the molecular level. The results showed that transition metal borides, called Mo4/3B2-x nanoscaffolds, could mimic superoxide dismutase and glutathione peroxidase to eliminate excess reactive oxygen species (ROS) in the wound microenvironment. During the therapeutic process, the Mo4/3B2-x nanoscaffold could facilitate the regeneration of wounds and removal of scars by regulating the biosynthesis of collagen, fibers, and blood vessels at the pathological, imaging, and molecular levels. Subsequent metabolomics study revealed that the Mo4/3B2-x nanoscaffold effectively ameliorated metabolic disorders in both wound and scar microenvironments through regulating ROS-related pathways including the amino acid metabolic process (including glycine and serine metabolism and glutamate metabolism) and the purine metabolic process. This study is anticipated to illuminate the potential clinical application of the Mo4/3B2-x nanoscaffold as an effective therapeutic agent in traumatic diseases and provide insights into the development of analytical methodology for interrogating wound healing and scar removal-related metabolic mechanisms.

Conservation and specialization of the Ycf2-FtsHi chloroplast protein import motor in green algae.

The protein import motor in chloroplasts plays a pivotal role in their biogenesis and homeostasis by driving the translocation of preproteins into chloroplasts. While the Ycf2-FtsHi complex serves as the import motor in land plants, its evolutionary conservation, specialization, and mechanisms across photosynthetic organisms are largely unexplored. Here, we isolated and determined the cryogenic electron microscopy (cryo-EM) structures of the native Ycf2-FtsHi complex from Chlamydomonas reinhardtii, uncovering a complex composed of up to 19 subunits, including multiple green-algae-specific components. The heterohexameric AAA+ ATPase motor module is tilted, potentially facilitating preprotein handover from the translocon at the inner chloroplast membrane (TIC) complex. Preprotein interacts with Ycf2-FtsHi and enhances its ATPase activity in vitro. Integrating Ycf2-FtsHi and translocon at the outer chloroplast membrane (TOC)-TIC supercomplex structures reveals insights into their physical and functional interplay during preprotein translocation. By comparing these findings with those from land plants, our study establishes a structural foundation for understanding the assembly, function, evolutionary conservation, and diversity of chloroplast protein import motors.

Association of molar incisor hypomineralization with hypomineralized second primary molars: an updated systematic review with a meta-analysis and trial sequential analysis.

INTRODUCTION: There is a correlation between molar incisor hypomineralization (MIH) and hypomineralized second primary molars (HSPM), but this relationship has not been definitively confirmed. The purpose of this systematic review and meta-analysis was to reevaluate whether children with HSPM are more affected by MIH than non-HSPM children. METHODS: A systematic search was conducted in four databases (PubMed, Embase, Web of Science and the Cochrane Library) for literature, published up to December 2022. Two independent reviewers conducted the study search and screening, quality assessment, and data extraction according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. The risk of bias assessment of all included cohort studies and case-control studies were assessed by the Newcastle-Ottawa Scale (NOS), and cross-sectional studies were assessed using the Agency for Healthcare Research Quality (AHRQ) scale. RevMan 5.4 software was used for all data analyses, with odds ratios (ORs) and 95% confidence intervals (CIs) as the effect measures. Sensitivity and subgroup analyses were conducted to identify the potential sources of heterogeneity among the studies. Publication bias was tested and corrected by funnel plots and Egger's test. Trial sequential analysis (TSA) was performed using TSA 0.9.5.10 Beta software to control for type-1 and type-2 errors. RESULTS: A total of 12 studies involving 8,944 children were included in this meta-analysis. Compared with the non-HSPM group, the HSPM group had an increased likelihood of MIH (OR = 10.90, 95% CI = 4.59-25.89, P <0.05). All the included studies were of moderate-to-high quality. TSA and sensitivity analyses suggested the robustness of this outcome. CONCLUSION: This systematic review demonstrated a certain correlation between HSPM and MIH, suggesting that HSPM can play a predictive role in the occurrence of MIH. Further high-quality, multicenter and large-sample longitudinal studies are highly recommended.

Polarization-Switchable Electrochemistry of 2D Layered Bi2O2Se Bifunctional Microreactors by Ferroelectric Modulation.

Ferroelectric catalysts are known for altering surface catalytic activities by changing the direction of their electric polarizations. This study demonstrates polarization-switchable electrochemistry using layered bismuth oxyselenide (L-Bi2O2Se) bifunctional microreactors through ferroelectric modulation. A selective-area ionic liquid gating is developed with precise control over the spatial distribution of the dipole orientation of L-Bi2O2Se. On-chip microreactors with upward polarization favor the oxygen evolution reaction, whereas those with downward polarization prefer the hydrogen evolution reaction. The microscopic origin behind polarization-switchable electrochemistry primarily stems from enhanced surface adsorption and reduced energy barriers for reactions, as examined by nanoscale scanning electrochemical cell microscopy. Integrating a pair of L-Bi2O2Se microreactors consisting of upward or downward polarizations demonstrates overall water splitting in a full-cell configuration based on a bifunctional catalyst. The ability to modulate surface polarizations on a single catalyst via ferroelectric polarization switching offers a pathway for designing catalysts for water splitting.

Reduced insulin clearance in paediatric metabolic (dysfunction)-associated fatty liver disease and its dual role in beta-cell offload and diabetes risk.

AIM: Diminished hepatic insulin clearance (HIC) is observed in obese adults and is presumed to be mediated by fatty liver. However, few reports have examined HIC in Chinese children with metabolic (dysfunction)-associated fatty liver disease (MAFLD). This study aimed to investigate the correlation between HIC, insulin sensitivity and ß-cell function in obese Chinese children with MAFLD. METHODS: In total, 204 obese children (74 MAFLD) aged 4-17 years were enrolled into this study. HIC, insulin sensitivity and ß-cell function were calculated using the oral glucose tolerance test (1.75 g/kg body weight). Correlation analyses between the HIC and clinical variables were performed using Pearson's product-moment correlation coefficients. HIC and glucose homeostasis were assessed in a high-fat diet mouse model, and liver samples were collected for molecular analysis. RESULTS: Obese children with MAFLD exhibited significantly lower HIC (AUCC-peptide/insulin ratio, p = 0.0019), higher insulin resistance (homeostatic model assessment of insulin resistance, p = 0.002), and increased compensatory ß-cell function (homeostatic model assessment-ß, p = 0.046) than obese children without liver involvement. Notably, HIC was negatively correlated with insulin sensitivity (r = -0.5035, p < 0.0001) and ß-cell function (r = -0.4576, p < 0.0001). However, pancreatic ß-cell dysfunction (p = 0.046) was accompanied by future reduced HIC (p = 0.034) in children with MAFLD in prediabetes. In a high-fat diet mouse model, MAFLD mice showed a 50% reduction in insulin-degrading enzyme expression, consistent with the observed decrease in HIC. CONCLUSIONS: A lower HIC may offload pancreatic ß-cells at an early stage. However, obese children with MAFLD are at risk of developing diabetes, and preventive efforts should be prioritized.

The KEAP1/PGAM5/AIFM1-Mediated oxeiptosis pathway in Alzheimer's disease.

BACKGROUND: Alzheimer's Disease (AD) is a neurodegenerative disease with mitochondrial dysfunction and oxidative stress. Oxeiptosis is a cell death pathway sensitive to reactive oxygen species (ROS). This study investigates the role of oxeiptosis pathway and mitochondrial damage in AD. METHODS: An AD model was developed in C57BL/6 mice by injecting Aß1-42 oligomers into the brain. Cognitive function was tested using the Morris water maze. Exposure of HT22 mouse hippocampal neurons to H2O2 induces oxidative stress. Protein levels of KEAP1, PGAM5 and AIFM1 were analyzed by western blot, and mitochondrial damage was observed with electron microscopy. Cell survival rates were using the CCK8 assay and flow cytometry after knocking down KEAP1, PGAM5 and AIFM1. RESULTS: The protein concentrations of KEAP1, PGAM5 and AIFM1 were found to be elevated in the hippocampal tissues of AD mice compared to control group, accompanied by mitochondrial damage in the hippocampal neurons of the AD group. Similarly, in the HT22 oxidative stress model, there was an increase in the protein levels of KEAP1, PGAM5 and AIFM1, along with observed mitochondrial damage. Following individual and combined knockdown of KEAP1, PGAM5 and AIFM1, cell survival rates under oxidative stress conditions were higher compared to H2O2 group, with no significant difference in cell survival rates among the knockdown groups. CONCLUSION: This research underscores the critical role of the KEAP1/PGAM5/AIFM1-mediated oxeiptosis pathway in neuronal cell death, offering insights into potential therapeutic targets for mitigating neurodegeneration in AD.

Damage-programmable design of metamaterials achieving crack-resisting mechanisms seen in nature.

The fracture behaviour of artificial metamaterials often leads to catastrophic failures with limited resistance to crack propagation. In contrast, natural materials such as bones and ceramics possess microstructures that give rise to spatially controllable crack path and toughened material resistance to crack advances. This study presents an approach that is inspired by nature's strengthening mechanisms to develop a systematic design method enabling damage-programmable metamaterials with engineerable microfibers in the cells that can spatially program the micro-scale crack behaviour. Machine learning is applied to provide an effective design engine that accelerate the generation of damage-programmable cells that offer advanced toughening functionality such as crack bowing, crack deflection, and shielding seen in natural materials; and are optimised for a given programming of crack path. This paper shows that such toughening features effectively enable crack-resisting mechanisms on the basis of the crack tip interactions, crack shielding, crack bridging and synergistic combinations of these mechanisms, increasing up to 1,235% absorbed fracture energy in comparison to conventional metamaterials. The proposed approach can have broad implications in the design of damage-tolerant materials, and lightweight engineering systems where significant fracture resistances or highly programmable damages for high performances are sought after.

Differentiating Definite and Probable Ménière Disease: A Comprehensive Evaluation of Audio-Vestibular Function Testing Combined with Inner Ear MRI.

OBJECTIVES: To evaluate the differences between audio-vestibular function testing and inner ear gadolinium magnetic resonance imaging (MRI) in distinguishing definite Ménière disease (DMD) and probable Ménière disease (PMD), and to provide a reference for early clinical diagnosis and intervention. METHODS: A total of 116 patients diagnosed with DMD (n = 80) and PMD (n = 36) were enrolled. The differences in the results of pure tone audiometry, caloric test, and tympanic injection of gadolinium for contrast-enhanced MRI between the two groups were compared and analyzed. Parameters that could differentiate between the two conditions were identified, and the sensitivity and specificity and the area under the curve (AUC) of individual and combined indices in the differential diagnosis of DMD and PMD were evaluated. RESULTS: The hearing threshold and hearing asymmetry rate of the DMD group were significantly higher than those of the PMD group (p < 0.001), 98.8% and 30.6%, respectively. The abnormal rates of canal paresis (CP) and severity of endolymphatic hydrops in the DMD group were higher than those in the PMD group (p < 0.05). When combined with high-frequency hearing thresholds, hearing asymmetry, hearing curve type, endolymphatic hydrops, and abnormal CP, the diagnostic accuracy of DMD was improved compared to using high-frequency alone (p < 0.05). CONCLUSION: This study showed that PMD and DMD may represent two different stages in the development of MD disease. The comprehensive assessment of audio-vestibular function testing and inner ear MRI proves beneficial for early diagnosis, potentially contributing to the preservation of inner ear function.

Construction of portable hydrogel kits with self-ratio optical bimodal detection and smartphone imaging for on-site nitrite screening.

Accurate on-site detection of nitrite in complex matrices remains a significant challenge. Herin, we construct a self-ratio optical bimodal portable kit via co-assembling NaErF4:0.5%Tm@NaYF4@NaYbF4:0.5%Tm@NaYF4 (Er:Tm@Yb:Tm) and nitrogen-doped carbon platinum nanomaterials (Pt/CN) in sodium alginate (SA) hydrogel. Pt/CN nanomaterials are synthesized by high-temperature sintering using a zinc-based zeolite imidazolium framework as a sacrificial template. The Pt/CN nanozyme possesses excellent oxidase-like activity to produce the oxidation state 3,3',5,5'-tetramethylbenzidine (oxTMB). Nitrite mediates diazotization of oxTMB to trigger the change of absorption signals, accompanying the ratio fluorescence response of the Er:Tm@Yb:Tm. Crucially, Er:Tm@Yb:Tm and Pt/CN are embedded in SA hydrogel to fabricate a portable kit with efficient and sensitive performance. An image processing algorithm is used to analyze the nitrite-induced signal change of the portable hydrogel kit, resulting in detection limits of 0.63 µM. This method has great potential for point-of-care applications due to its reliability, long-term stability, accuracy, sensitivity, and portability.

Bruton's tyrosine kinase inhibition ameliorated neuroinflammation during chronic white matter ischemia.

Chronic cerebral hypoperfusion (CCH), a disease afflicting numerous individuals worldwide, is a primary cause of cognitive deficits, the pathogenesis of which remains poorly understood. Bruton's tyrosine kinase inhibition (BTKi) is considered a promising strategy to regulate inflammatory responses within the brain, a crucial process that is assumed to drive ischemic demyelination progression. However, the potential role of BTKi in CCH has not been investigated so far. In the present study, we elucidated potential therapeutic roles of BTK in both in vitro hypoxia and in vivo ischemic demyelination model. We found that cerebral hypoperfusion induced white matter injury, cognitive impairments, microglial BTK activation, along with a series of microglia responses associated with inflammation, oxidative stress, mitochondrial dysfunction, and ferroptosis. Tolebrutinib treatment suppressed both the activation of microglia and microglial BTK expression. Meanwhile, microglia-related inflammation and ferroptosis processes were attenuated evidently, contributing to lower levels of disease severity. Taken together, BTKi ameliorated white matter injury and cognitive impairments induced by CCH, possibly via skewing microglia polarization towards anti-inflammatory and homeostatic phenotypes, as well as decreasing microglial oxidative stress damage and ferroptosis, which exhibits promising therapeutic potential in chronic cerebral hypoperfusion-induced demyelination.

Upconversion-based chiral nanoprobe for highly selective dual-mode sensing and bioimaging of hydrogen sulfide in vitro and in vivo.

Chiral assemblies have become one of the most active research areas due to their versatility, playing an increasingly important role in bio-detection, imaging and therapy. In this work, chiral UCNPs/CuxOS@ZIF nanoprobes are prepared by encapsulating upconversion nanoparticles (UCNPs) and CuxOS nanoparticles (NPs) into zeolitic imidazolate framework-8 (ZIF-8). The novel excited-state energy distribution-modulated upconversion nanostructure (NaYbF4@NaYF4: Yb, Er) is selected as the fluorescence source and energy donor for highly efficient fluorescence resonance energy transfer (FRET). CuxOS NP is employed as chiral source and energy acceptor to quench upconversion luminescence (UCL) and provide circular dichroism (CD) signal. Utilizing the natural adsorption and sorting advantages of ZIF-8, the designed nanoprobe can isolate the influence of other common disruptors, thus achieve ultra-sensitive and highly selective UCL/CD dual-mode quantification of H2S in aqueous solution and in living cells. Notably, the nanoprobe is also capable of in vivo intra-tumoral H2S tracking. Our work highlights the multifunctional properties of chiral nanocomposites in sensing and opens a new vision and idea for the preparation and application of chiral nanomaterials in biomedical and biological analysis.