Sensitive colorimetric detection of heparin using reverse modulation of peroxidase- and oxidase-mimetic activities in Fe3O4@PDA@MnO2 nanocomposites.

Heparin, a widely studied glycosaminoglycan, plays crucial roles in the regulation of various physiological and pathological processes. Therefore, it's important to develop highly selective and sensitive methods for convenient monitoring of heparin levels in biological systems. We report the design and synthesis of Fe3O4@PDA@MnO2 nanoparticles (FPM-NPs), which exhibit dual enzymatic activities, enabling quantitative detection of heparin. The FPM-NPs feature a unique tri-layer spherical shell structure, possessing both peroxidase-like and oxidase-like activities, and catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in the presence or absence of H2O2. Remarkably, upon co-incubated with heparin, the oxidase activity of FPM-NPs decreases, while the peroxidase activity increases. By leveraging these dual enzymatic properties of FPM-NPs, a highly sensitive and specific colorimetric detection of heparin is achieved, with a detection limit reaching 6.51 nM and a good linear response to quantify heparin ranging 10-800 nM. Additionally, the developed FPM-NPs are successfully applied to measure heparin in fetal bovine serum samples. We also extend this detection method to a paper-based chip, enabling portable detection of heparin through grayscale analysis of mobile phone photographs. The multi-nanozyme-based heparin detection approach provides a new perspective for future research on expanding the application of nanocomposite materials in biomedical detection and analysis.

Experimental Catalytic Amplification of Asymmetry.

The manipulation and transformation of quantum resources are key parts of quantum mechanics. Among them, asymmetry is one of the most useful operational resources, which is widely used in quantum clocks, quantum metrology, and other tasks. Recent studies have shown that the asymmetry of quantum states can be significantly amplified with the assistance of correlating catalysts that are finite-dimensional auxiliaries. In the experiment, we perform translationally invariant operations, ensuring that the asymmetric resources of the entire system remain nonincreasing, on a composite system composed of a catalytic system and a quantum system. The experimental results demonstrate an asymmetry amplification of 0.0172±0.0022 in the system following the catalytic process. Our Letter showcases the potential of quantum catalytic processes and is expected to inspire further research in the field of quantum resource theories.

Tea polyphenol nano-crosslinked dynamical hyaluronic acid-based hydrogel for diabetic wound healing.

Diabetic wound healing remains a significant clinical challenge for the complex wound microenvironment characterized by oxidative stress, inflammation, and bacterial infection. To address these challenges, we present a novel hydrogel incorporates tea polyphenol-stabilized silver nanoparticles (TP@Ag NPs) into a dynamic hyaluronic acid-phenylboronic acid network crosslinked via borate ester bonds. This design leverages the inherent biocompatibility and biodegradability of hyaluronic acid alongside the antioxidant, anti-inflammatory, and antibacterial properties of tea polyphenols and silver nanoparticles. The HP-TP@Ag hydrogel exhibited glucose-responsive degradation and TP@Ag NPs release, enabling targeted delivery within the diabetic wound microenvironment. In vitro assays demonstrated the hydrogel's potent antioxidant activity, effectively scavenging ROS and protecting both HaCaT and RAW264.7 cells from oxidative stress. Furthermore, the HP-TP@Ag hydrogel significantly suppressed the production of pro-inflammatory cytokines and exhibited robust antibacterial activity against both E. coli and S. aureus. In vivo studies using a diabetic mouse model revealed accelerated wound closure, reduced inflammation, enhanced collagen deposition, and promoted angiogenesis and tissue remodeling in HP-TP@Ag hydrogel-treated wounds. These findings highlight the promise of HP-TP@Ag hydrogel as an advanced wound dressing for effective diabetic wound management, offering a synergistic approach to overcome the multifaceted challenges associated with this complex condition.

Downregulation of the GhROD1 Gene Improves Cotton Fiber Fineness by Decreasing Acyl Pool Saturation, Stimulating Small Heat Shock Proteins (sHSPs), and Reducing H2O2 Production.

Cotton fiber is one of the most important natural fiber sources in the world, and lipid metabolism plays a critical role in its development. However, the specific role of lipid molecules in fiber development and the impact of fatty acid alterations on fiber quality remain largely unknown. In this study, we demonstrate that the downregulation of GhROD1, a gene encoding phosphatidylcholine diacylglycerol cholinephosphotransferase (PDCT), results in an improvement of fiber fineness. We found that GhROD1 downregulation significantly increases the proportion of linoleic acid (18:2) in cotton fibers, which subsequently upregulates genes encoding small heat shock proteins (sHSPs). This, in turn, reduces H2O2 production, thus delaying secondary wall deposition and leading to finer fibers. Our findings reveal how alterations in linoleic acid influence cellulose synthesis and suggest a potential strategy to improve cotton fiber quality by regulating lipid metabolism pathways.

Tolvaptan and the role of kidney aquaporin-2 abundance in managing volume overload in patients with CKD.

Objective: This retrospective study evaluated tolvaptan's efficacy, safety, and predictive indicators in managing volume overload in chronic kidney disease (CKD) patients. Methods: CKD patients with volume overload, treated with loop diuretics alone or with tolvaptan at Zhongda Hospital, Southeast University, from 1 March 2022 to 31 December 2023, were included. Patients were divided into loop diuretic (Group C) and loop diuretic combined with tolvaptan (Group T) cohorts. Primary outcomes included volume control, changes in weight, urine output, and laboratory parameters within 1 week post-medication. Adverse events such as hypernatremia and hyperkalemia, etc., were recorded. We further conducted immunohistochemical staining of renal biopsy tissues to investigate the roles of aquaporin-2 (AQP2) in the collecting duct and plasma albumin in predicting the efficacy of tolvaptan. Results: Of 174 CKD patients with volume overload, 108 (67.07%) were male. Group C and Group T each comprised 87 patients. At baseline, no significant differences in urine output and weight were noted. By day 3, Group T exhibited a greater increase in urine output (P < .001) and weight reduction (P < .001). At day 7, Group T maintained more significant diuretic effects (P < .001). More Group C patients required ultrafiltration therapy (P = .040). Adverse event rates did not significantly differ. Notably, AQP2 expression in the collecting duct may predict tolvaptan responsiveness, while plasma albumin did not affect efficacy. Conclusion: Tolvaptan showed efficacy and safety in managing volume overload in CKD patients. The expression of AQP2 in the collecting duct could predict tolvaptan's efficacy.This study protocol was approved by the Ethics Committee of Zhongda Hospital Affiliated to Southeast University (Approval No. 2023ZDSYLL180-P01, Clinical Trial Registration No. ChiCTR2300075274, Trial Registration Link: https://www.chictr.org.cn/guide.html).

Nonlocal photonic quantum gates over 7.0 km.

Quantum networks provide a prospective paradigm to connect separated quantum nodes, which relies on the distribution of long-distance entanglement and active feedforward control of qubits between remote nodes. Such approaches can be utilized to construct nonlocal quantum gates, forming building blocks for distributed quantum computing and other novel quantum applications. However, these gates have only been realized within single nodes or between nodes separated by a few tens of meters, limiting the ability to harness computing resources in large-scale quantum networks. Here, we demonstrate nonlocal photonic quantum gates between two nodes spatially separated by 7.0 km using stationary qubits based on multiplexed quantum memories, flying qubits at telecom wavelengths, and active feedforward control based on field-deployed fibers. Furthermore, we illustrate quantum parallelism by implementing the Deutsch-Jozsa algorithm and the quantum phase estimation algorithm between the two remote nodes. These results represent a proof-of-principle demonstration of quantum gates over metropolitan-scale distances and lay the foundation for the construction of large-scale distributed quantum networks relying on existing fiber channels.

Rapid parallel blood typing on centrifugal microfluidic platform by microcolumn gel immunoassay.

Microcolumn gel immunoassay (MGIA) has the ability to meet the requirements of clinical diagnosis due to its reliable sensitivity and accuracy. However, traditional MGIA exhibits limitations including inadequate portability, low throughput, and extended analysis time. To address these challenges, we combined MGIA with microfluidic technology, demonstrating a centrifugal microfluidic-based microcolumn gel immunoassay (µMGIA) platform for blood typing of clinical samples. Experimental results indicate that the µMGIA platform can simultaneously detect six blood group antigens in five clinical blood samples within 2 min. Notably, it offers comprehensive detection of ABO blood group antigens and Rh blood group antigens with 100 % accuracy, outperforming the traditional slide method. The integration of microfluidic technology with MGIA circumvents the constraints of traditional methods, providing a new avenue for blood typing and immunoanalysis of clinical samples.

Drip-Dry Strategy Assisted Blu-Ray Disc Biosensor for Fast Point of Care Testing.

Discs and numerous other consumer products have been developed for point of care testing (POCT) to replace traditional large and expensive biochemical devices in certain scenarios. Herein, we propose a drip-dry strategy (2D strategy) assisted Blu-ray disc (BD) biosensor, termed BDB, for rapid and portable POCT within 30 min with the cost of a single test < $1. The platform utilizes the covered area formed by the deposition of the substance to be measured on the activated BD surface after the evaporation of water and realizes the quantitative detection of the target through the error readout of free disc quality diagnosis software. As a proof of concept, we first demonstrated the feasibility of direct quantitative detection of substances in solution in a single system through the detection of pure proteins avoiding colorimetric reagent used in traditional optical detection. For the complex mixed systems, we then innovatively utilize the principle that soluble targets promote/inhibit the dissolution of insoluble precipitates to achieve specific detection of targets and successfully apply BDB to the indirect quantitative detection of glutathione (GSH) with LOD of 0.447 mM in the range of 2-16 mM and organophosphorus pesticides (OPs) with LOD of 2.122 × 10-7 M in the range of 1.289 × 10-7-1.289 × 10-4 M. The BDB is widely applicable, easy to operate, and less time-consuming, which is anticipated to provide an alternative method for early, on-site detection or screening.

The multifaceted effects of mitochondria in kidney diseases.

Mitochondria serve as the primary site for aerobic respiration within cells, playing a crucial role in maintaining cellular homeostasis. To maintain homeostasis and meet the diverse demands of the cells, mitochondria have evolved intricate systems of quality control, mainly including mitochondrial dynamics, mitochondrial autophagy (mitophagy) and mitochondrial biogenesis. The kidney, characterized by its high energy requirements, is particularly abundant in mitochondria. Interestingly, the mitochondria display complex behaviors and functions. When the kidney is suffered from obstructive, ischemic, hypoxic, oxidative, or metabolic insults, the dysfunctional mitochondrial derived from the defects in the mitochondrial quality control system contribute to cellular inflammation, cellular senescence, and cell death, posing a threat to the kidney. However, in addition to causing injury to the kidney in several cases, mitochondria also exhibit protective effect on the kidney. In recent years, accumulating evidence indicated that mitochondria play a crucial role in adaptive repair following kidney diseases caused by various etiologies. In this article, we comprehensively reviewed the current understanding about the multifaceted effects of mitochondria on kidney diseases and their therapeutic potential.

Renal tubular epithelial cells response to injury in acute kidney injury.

Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid and significant decrease in renal function that can arise from various etiologies, and is associated with high morbidity and mortality. The renal tubular epithelial cells (TECs) represent the central cell type affected by AKI, and their notable regenerative capacity is critical for the recovery of renal function in afflicted patients. The adaptive repair process initiated by surviving TECs following mild AKI facilitates full renal recovery. Conversely, when injury is severe or persistent, it allows the TECs to undergo pathological responses, abnormal adaptive repair and phenotypic transformation, which will lead to the development of renal fibrosis. Given the implications of TECs fate after injury in renal outcomes, a deeper understanding of these mechanisms is necessary to identify promising therapeutic targets and biomarkers of the repair process in the human kidney.

Identification of a Novel ECM Remodeling Macrophage Subset in AKI to CKD Transition by Integrative Spatial and Single-Cell Analysis.

The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) is a critical clinical issue. Although previous studies have suggested macrophages as a key player in promoting inflammation and fibrosis during this transition, the heterogeneity and dynamic characterization of macrophages are still poorly understood. Here, we used integrated single-cell RNA sequencing and spatial transcriptomic to characterize the spatiotemporal heterogeneity of macrophages in murine AKI-to-CKD model of unilateral ischemia-reperfusion injury. A marked increase in macrophage infiltration at day 1 was followed by a second peak at day 14 post AKI. Spatiotemporal profiling revealed that injured tubules and macrophages co-localized early after AKI, whereas in late chronic stages had spatial proximity to fibroblasts. Further pseudotime analysis revealed two distinct lineages of macrophages in this transition: renal resident macrophages differentiated into the pro-repair subsets, whereas infiltrating monocyte-derived macrophages contributed to chronic inflammation and fibrosis. A novel macrophage subset, extracellular matrix remodeling-associated macrophages (EAMs) originating from monocytes, linked to renal fibrogenesis and communicated with fibroblasts via insulin-like growth factors (IGF) signalling. In sum, our study identified the spatiotemporal dynamics of macrophage heterogeneity with a unique subset of EAMs in AKI-to-CKD transition, which could be a potential therapeutic target for preventing CKD development.

Electro-optically tunable optical delay on a lithium niobate photonic chip.

An approach for continuous tuning of on-chip optical delay with a microring resonator is proposed and demonstrated. By introducing an electro-optically tunable waveguide coupler, the bus waveguide to the resonance coupling can be effectively tuned from the under-coupling regime to the over-coupling regime. The optical delay is experimentally characterized by measuring the relative phase shift between lasers and shows a large dynamic range of delay from -600 to 600 ps and an efficient tuning of delay from -430 to -180 ps and from 40 to 240 ps by only a 5 V voltage.

Macrophage-derived exosomes promote telomere fragility and senescence in tubular epithelial cells by delivering miR-155.

BACKGROUND: Chronic kidney disease (CKD) is highly prevalent worldwide, and its global burden is substantial and growing. CKD displays a number of features of accelerated senescence. Tubular cell senescence is a common biological process that contributes to CKD progression. Tubulointerstitial inflammation is a driver of tubular cell senescence and a common characteristic of CKD. However, the mechanism by which the interstitial inflammation drives tubular cell senescence remains unclear. This paper aims to explore the role of exosomal miRNAs derived from macrophages in the development of tubular cell senescence. METHODS: Among the identified inflammation-related miRNAs, miR-155 is considered to be one of the most important miRNAs involved in the inflammatory response. Macrophages, the primary immune cells that mediate inflammatory processes, contain a high abundance of miR-155 in their released exosomes. We assessed the potential role of miR-155 in tubular cell senescence and renal fibrosis. We subjected miR-155-/- mice and wild-type controls, as well as tubular epithelial cells (TECs), to angiotensin II (AngII)-induced kidney injury. We assessed kidney function and injury using standard techniques. TECs were evaluated for cell senescence and telomere dysfunction in vivo and in vitro. Telomeres were measured by the fluorescence in situ hybridization. RESULTS: Compared with normal controls, miR-155 was up-regulated in proximal renal tubule cells in CKD patients and mouse models of CKD. Moreover, the expression of miR-155 was positively correlated with the extent of renal fibrosis, eGFR decline and p16INK4A expression. The overexpression of miR-155 exacerbated tubular senescence, evidenced by increased detection of p16INK4A/p21expression and senescence-associated ß-galactosidase activity. Notably, miR-155 knockout attenuates renal fibrosis and tubule cell senescence in vivo. Interestingly, once released, macrophages-derived exosomal miR-155 was internalized by TECs, leading to telomere shortening and dysfunction through targeting TRF1. A dual-luciferase reporter assay confirmed that TRF1 was the direct target of miR-155. Thus, our study clearly demonstrates that exosomal miR-155 may mediate communication between macrophages and TECs, subsequently inducing telomere dysfunction and senescence in TECs. CONCLUSIONS: Our work suggests a new mechanism by which macrophage exosomes are involved in the development of tubule senescence and renal fibrosis, in part by delivering miR-155 to target TRF1 to promote telomere dysfunction. Our study may provide novel strategies for the treatment of AngII-induced kidney injury.

Roxadustat on Renal Anemia with Macroinflammation: A Retrospective Cohort Study.

Introduction: Roxadustat, the first-in-class drug for the treatment of renal anemia, has demonstrated efficacy in renal anemia with microinflammation. Additional data are needed regarding the efficacy of roxadustat on renal anemia with systemic macroinflammation. Methods: Three cohorts of renal anemia based on the basic level of high-sensitivity CRP were included. Patients with hsCRP ≤2 mg/L were selected as non-inflammation (NI) group; 2< hsCRP ≤10 mg/L as microinflammation (MI) group; hsCRP≥10 mg/L as macroinflammation (MA) group. Patients received oral roxadustat three times per week for 52 weeks. The primary end point was the hemoglobin level over weeks 12-52. The second end point was the cumulative proportion of patients achieving hemoglobin response by the end of week 12. Results: A total of 107 patients with chronic kidney diseases (CKDs) were enrolled. Overall, the baseline hemoglobin level of patients was 79.99 ± 11.20 g/L. Roxadustat could significantly increase the hemoglobin level in all of the three groups and did not show any significant difference (p > 0.05, respectively). Meanwhile, compared with that of the NI group, there was no significant difference in hemoglobin response rate in the MA group both at week 12 (p = 0.06; 95% confidence interval [CI], 0.9531-13.75) and week 52 (p = 0.37; 95% CI, 0.5080-7.937). Moreover, the hemoglobin response was independent of baseline hsCRP level (p = 0.72, 95% CI, -0.1139 to 0.0794). More importantly, roxadustat significantly reduced ferritin and serum iron levels and increased total iron-binding capacity in the three groups, which showed no significant differences among the three groups (p > 0.05, respectively). Conclusion: Roxadustat significantly improves anemia in CKD patients with systemic macroinflammation.

Fully Integrated and High-Throughput Microfluidic System for Multiplexed Point-Of-Care Testing.

For every epidemic outbreak, the prevention and treatments in resource-limited areas are always out of reach. Critical to this is that high accuracy, stability, and more comprehensive analytical techniques always rely on expensive and bulky instruments and large laboratories. Here, a fully integrated and high-throughput microfluidic system is proposed for ultra-multiple point-of-care immunoassay, termed Dac system. Specifically, the Dac system only requires a handheld portable device to automatically recycle repetitive multi-step reactions including on-demand liquid releasing, dispensing, metering, collecting, oscillatory mixing, and discharging. The Dac system performs high-precision enzyme-linked immunosorbent assays for up to 17 samples or targets simultaneously on a single chip. Furthermore, reagent consumption is only 2% compared to conventional ELISA, and microbubble-accelerated reactions shorten the assay time by more than half. As a proof of concept, the multiplexed detections are achieved by detecting at least four infection targets for two samples simultaneously on a singular chip. Furthermore, the barcode-based multi-target results can rapidly distinguish between five similar cases, allowing for accurate therapeutic interventions. Compared to bulky clinical instruments, the accuracy of clinical inflammation classification is 92.38% (n = 105), with a quantitative correlation coefficient of R2 = 0.9838, while the clinical specificity is 100% and the sensitivity is 98.93%.

A Chinese Multi-Specialty Delphi Consensus to Optimize RAASi Usage and Hyperkalaemia Management in Patients with Chronic Kidney Disease and Heart Failure.

Objective Variations are present in common clinical practices regarding best practice in managing hyperkalaemia (HK), there is therefore a need to establish a multi-specialty approach to optimal renin-angiotension-aldosterone system inhibitors (RAASi) usage and HK management in patients with chronic kidney disease (CKD) & heart failure (HF).This study aimed to establish a multi-speciality approach to the optimal use of RAASi and the management of HK in patients with CKD and HF. Methods A steering expert group of cardiology and nephrology experts across China were convened to discuss challenges to HK management through a nominal group technique. The group then created a list of 41 statements for a consensus questionnaire, which was distributed for a further survey in extended panel group of cardiologists and nephrologists across China. Consensus was assessed using a modified Delphi technique, with agreement defined as "strong" (≥75% and <90%) and "very strong" (≥90%). The steering group, data collection, and analysis were aided by an independent facilitator. Results A total of 150 responses from 21 provinces across China were recruited in the survey. Respondents were comprised of an even split (n=75, 50%) between cardiologists and nephrologists. All 41 statements achieved the 75% consensus agreement threshold, of which 27 statements attained very strong consensus (≥90% agreement) and 14 attained strong consensus (agreement between 75% and 90%). Conclusion Based on the agreement levels from respondents, the steering group agreed a set of recommendations intended to improve patient outcomes in the use of RAASi therapy and HK management in China.

CD8 T cells induce the peritubular capillary rarefaction during AKI to CKD transition.

Acute kidney injury (AKI) transformed to chronic kidney disease (CKD) is a critical clinical issue characterized by tubulointerstitial inflammation (TII) and fibrosis. However, the exact mechanism remains largely unclear. In this study, we used single-cell RNA sequencing (scRNA-seq) to obtain a high-resolution profile of T cells in AKI to CKD transition with a mice model of unilateral ischemia-reperfusion injury (uIRI). We found that T cells accumulated increasingly with the progression of AKI to CKD, which was categorized into 9 clusters. A notably increased proportion of CD8 T cells via self-proliferation occurred in the early stage of AKI was identified. Further study revealed that the CD8 T cells were recruited through CXCL16-CXCR6 pathway mediated by macrophages. Notably, CD8 T cells induced endothelial cell apoptosis via Fas ligand-Fas signaling. Consistently, increased CD8 T cell infiltration accompanied with peritubular capillaries (PTCs) rarefaction was observed in uIRI mice. More impressively, the loss of PTCs and renal fibrosis was remarkably ameliorated after the elimination of CD8 T cells. In summary, our study provides a novel insight into the role of CD8 T cells in the transition from AKI to CKD via induction of PTCs rarefaction, which could suggest a promising therapeutic target for AKI.

Erratum: Exosomal miR-125b-5p deriving from mesenchymal stem cells promotes tubular repair by suppression of p53 in ischemic acute kidney injury: Erratum.

[This corrects the article DOI: 10.7150/thno.54550.].

Observation of Diverse Asymmetric Structures in High-Dimensional Einstein-Podolsky-Rosen Steering.

Einstein-Podolsky-Rosen (EPR) steering, a distinctive quantum correlation, reveals a unique and inherent asymmetry. This research delves into the multifaceted asymmetry of EPR steering within high-dimensional quantum systems, exploring both theoretical frameworks and experimental validations. We introduce the concept of genuine high-dimensional one-way steering, wherein a high Schmidt number of bipartite quantum states is demonstrable in one steering direction but not reciprocally. Additionally, we explore two criteria to certify the lower and upper bounds of the Schmidt number within a one-sided device-independent context. These criteria serve as tools for identifying potential asymmetric dimensionality of EPR steering in both directions. By preparing two-qutrit mixed states with high fidelity, we experimentally observe asymmetric structures of EPR steering in the C^{3}⊗C^{3} Hilbert space. Our Letter offers new perspectives to understand the asymmetric EPR steering beyond qubits and has potential applications in asymmetric high-dimensional quantum information tasks.