Effective treatment of optic neuropathies by intraocular delivery of MSC-sEVs through augmenting the G-CSF-macrophage pathway.

Optic neuropathies, characterized by injury of retinal ganglion cell (RGC) axons of the optic nerve, cause incurable blindness worldwide. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) represent a promising "cell-free" therapy for regenerative medicine; however, the therapeutic effect on neural restoration fluctuates, and the underlying mechanism is poorly understood. Here, we illustrated that intraocular administration of MSC-sEVs promoted both RGC survival and axon regeneration in an optic nerve crush mouse model. Mechanistically, MSC-sEVs primarily targeted retinal mural cells to release high levels of colony-stimulating factor 3 (G-CSF) that recruited a neural restorative population of Ly6Clow monocytes/monocyte-derived macrophages (Mo/MΦ). Intravitreal administration of G-CSF, a clinically proven agent for treating neutropenia, or donor Ly6Clow Mo/MΦ markedly improved neurological outcomes in vivo. Together, our data define a unique mechanism of MSC-sEV-induced G-CSF-to-Ly6Clow Mo/MΦ signaling in repairing optic nerve injury and highlight local delivery of MSC-sEVs, G-CSF, and Ly6Clow Mo/MΦ as therapeutic paradigms for the treatment of optic neuropathies.

Upgrading Waste Polylactide via Catalyst-Controlled Tandem Hydrolysis-Oxidation.

As plastic waste pollution continues to pose significant challenges to our environment, it is crucial to develop eco-friendly processes that can transform plastic waste into valuable chemical products in line with the principles of green chemistry. One major challenge is breaking down plastic waste into economically valuable carbon resources. This however presents an opportunity for sustainable circular economies. In this regard, a flexible approach is presented that involves the use of supported-metal catalysts to selectively degrade polylactide waste using molecular oxygen. This protocol has several advantages, including its operation under organic solvent-free and mild conditions, simplicity of implementation, and high atom efficiency, resulting in minimal waste. This approach enables the chemical upcycling of polylactide waste into valuable chemicals such as pyruvic acid, acetic acid, or a mixture containing equimolar amounts of acetic acid and formaldehyde, providing a viable alternative for accessing key value-added feedstocks from waste and spent plastics.

Probing conformational kinetics of catalase with and without magnetic field by single-entity collision electrochemistry.

The conformational motions of enzymes are crucial for their catalytic activities, but these fluctuations are usually spontaneous and unsynchronized and thus difficult to obtain from ensemble-averaged measurements. Here, we employ label-free single-entity electrochemical measurements to monitor in real time the fluctuating enzymatic behavior of single catalase molecules toward the degradation of hydrogen peroxide. By probing the electrochemical signals of single catalase molecules at a carbon nanoelectrode, we were able to observe three distinct current traces that could be attributed to conformational changes on the sub-millisecond timescale. Whereas, nearly uniform single long peaks were observed for single catalase molecules under a moderate magnetic field due to the restricted conformational changes of catalase. By combining high-resolution current signals with a multiphysics simulation model, we studied the catalytic kinetics of catalase with and without a magnetic field, and further estimated the maximum catalytic rate and conformational transition rate. This work introduces a new complementary approach to existing single-molecule enzymology, giving further insight into the enzymatic reaction mechanism.

Directing (110) Oriented Lithium Deposition through High-flux Solid Electrolyte Interphase for Dendrite-free Lithium Metal Batteries.

Controlling lithium (Li) electrocrystallization with preferred orientation is a promising strategy to realize highly reversible Li metal batteries (LMBs) but lack of facile regulation methods. Herein, we report a high-flux solid electrolyte interphase (SEI) strategy to direct (110) preferred Li deposition even on (200)-orientated Li substrate. Bravais rule and Curie-Wulff principle are expanded in Li electrocrystallization process to decouple the relationship between SEI engineering and preferred crystal orientation. Multi-spectroscopic techniques combined with dynamics analysis reveal that the high-flux CF3 Si(CH3 )3 (F3 ) induced SEI (F3 -SEI) with high LiF and -Si(CH3 )3 contents can ingeniously accelerate Li+ transport dynamics and ensure the sufficient Li+ concentration below SEI to direct Li (110) orientation. The induced Li (110) can in turn further promote the surface migration of Li atoms to avoid tip aggregation, resulting in a planar, dendrite-free morphology of Li. As a result, our F3 -SEI enables ultra-long stability of Li||Li symmetrical cells for more than 336 days. Furthermore, F3 -SEI modified Li can significantly enhance the cycle life of Li||LiFePO4 and Li||NCM811 coin and pouch full cells in practical conditions. Our crystallographic strategy for Li dendrite suppression paves a path to achieve reliable LMBs and may provide guidance for the preferred orientation of other metal crystals.

Understanding Correlation between Magnetism and Electrocatalytic Hydrogen Evolution Based on Intrinsic Properties of Single MoS2 Entity.

Few-layered molybdenum chalcogenide (MoS2) has attracted considerable attention due to its defect-rich structure and active edge sites, triggering distinctive electrocatalysis and magnetism properties. Quantifying the intrinsic properties of a single entity is of paramount importance for clarifying the structure-activity correlation. Here, the intrinsic activities of single MoS2 flakes toward the hydrogen evolution reaction (HER) were investigated by single nanoparticle collision electrochemical measurements with and without a moderate magnetic field. Our results demonstrate that single bilayer MoS2 flakes show the highest HER performance and the greatest magnetic enhancement among bilayer-, trilayer-, and multilayer-MoS2 flakes. This is because bilayer MoS2 flakes possess abundantly exposed edge sites and sulfur vacancies, which simultaneously accelerate the reaction kinetics of HER and increase the ferromagnetism properties. This work gives new insight into providing specific guidance for the magnetic modulation of few-layered MoS2 and the design of highly effective MoS2-based electrocatalysts.

Confined Electrochemical Behaviors of Single Platinum Nanoparticles Revealing Ultrahigh Density of Gas Molecules inside a Nanobubble.

Understanding the basic physicochemical properties of gas molecules confined within nanobubbles is of fundamental importance for chemical and biological processes. Here, we successfully monitored the nanobubble-confined electrochemical behaviors of single platinum nanoparticles (PtNPs) at a carbon fiber ultramicroelectrode in HClO4 and H2O2 solution. Due to the catalytic decomposition of H2O2, a single oxygen nanobubble was formed on individual PtNPs to block the active surface of particles for proton reduction and to suppress their stochastic motion, resulting in significantly distinguished current traces. Furthermore, the combination of theoretical calculations and high-resolution electrochemical measurements allowed the nanobubble size and the oxygen gas density inside a single nanobubble to be quantified. Moreover, the ultrahigh oxygen density inside (1046 kg/m3) was revealed, indicating that gas molecules in a nanosized space existed with a high state of aggregation. Our approach sheds light on the gas aggregation behaviors of nanoscale bubbles using single-entity electrochemical measurements.

Selective Valorization of Glycerol to Formic Acid on a BiVO4 Photoanode through NiFe Phenolic Networks.

The integration of the glycerol oxidation reaction (GOR) with the hydrogen evolution reaction in photoelectrochemical (PEC) cells is a desirable alternative to PEC water splitting since a large quantity of glycerol is easily accessible as the byproduct from the biodiesel industry. However, the PEC valorization of glycerol to the value-added products suffers from low Faradaic efficiency and selectivity, especially in acidic conditions, which is beneficial for hydrogen production. Herein, by loading bismuth vanadate (BVO) with a robust catalyst composed of phenolic ligands (tannic acid) coordinated with Ni and Fe ions (TANF), we demonstrate a modified BVO/TANF photoanode for the GOR with a remarkable Faradaic efficiency of over 94% to value-added molecules in a 0.1 M Na2SO4/H2SO4 (pH = 2) electrolyte. The BVO/TANF photoanode achieved a high photocurrent of 5.26 mA·cm-2 at 1.23 V versus reversible hydrogen electrode under 100 mW/cm2 white light irradiation for formic acid production with 85% selectivity, equivalent to 573 mmol/(m2·h). Transient photocurrent and transient photovoltage techniques and electrochemical impedance spectroscopy along with intensity-modulated photocurrent spectroscopy indicated that the TANF catalyst could accelerate hole transfer kinetics and suppress charge recombination. Comprehensive mechanistic investigations reveal that the GOR is initiated by the photogenerated holes of BVO, while the high selectivity to formic acid is attributed to the selective adsorption of primary hydroxyl groups in glycerol on TANF. This study provides a promising avenue for highly efficient and selective formic acid generation from biomass in acid media via PEC cells.

Nitrogen-Neighbored Single-Cobalt Sites Enable Heterogeneous Oxidase-Type Catalysis.

The development of biomimetic catalytic systems that can imitate or even surpass natural enzymes remains an ongoing challenge, especially for bioinspired syntheses that can access non-natural reactions. Here, we show how an all-inorganic biomimetic system bearing robust nitrogen-neighbored single-cobalt site/pyridinic-N site (Co-N4/Py-N) pairs can act cooperatively as an oxidase mimic, which renders an engaged coupling of oxygen (O2) reduction with synthetically beneficial chemical transformations. By developing this broadly applicable platform, the scalable synthesis of greater than 100 industrially and pharmaceutically appealing O-silylated compounds including silanols, borasiloxanes, and silyl ethers via the unprecedented aerobic oxidation of hydrosilane under ambient conditions is demonstrated. Moreover, this heterogeneous oxidase mimic also offers the potential for expanding the catalytic scope of enzymatic synthesis. We anticipate that the strategy demonstrated here will pave a new avenue for understanding the underlying nature of redox enzymes and open up a new class of material systems for artificial biomimetics.

Rapid Screening of Bimetallic Electrocatalysts Using Single Nanoparticle Collision Electrochemistry.

The pace of nanomaterial discovery for high-performance electrocatalysts could be accelerated by the development of efficient screening methods. However, conventional electrochemical characterization via drop-casting is inherently inaccurate and time-consuming, as such ensemble measurements are serially performed through nanocatalyst synthesis, morphological characterization, and performance testing. Herein, we propose a rapid electrochemical screening method for bimetallic electrocatalysts that combines nanoparticle (NP) preparation and performance testing at the single NP level, thus avoiding any inhomogeneous averaging contribution. We employed single NP collision electrochemistry to realize in situ electrodeposition of a precisely tunable Pt shell onto individual parent NPs, followed by instantaneous electrocatalytic measurement of the newborn bimetallic core-shell NPs. We demonstrated the utility of this approach by screening bimetallic Au-Pt NPs and Ag-Pt NPs, thereby exhibiting promising electrocatalytic activity at optimal atomic ratios for methanol oxidation and oxygen reduction reactions, respectively. This work provides a new insight for the rapid screening of other bimetallic electrocatalysts.

The role of toll-like receptors (TLRs) in pan-cancer.

BACKGROUND: Toll-like receptors (TLRs) are important components of the innate and adaptive immune systems, and abnormal TLR expression has been linked to a variety of cancers. However, there was a lack of clarity on the association of TLR stimulation with the carcinogenesis of cancer. The study's goal was to analyse the clinical importance of TLRs expression at the mRNA level in pan-cancer datasets, as well as the link between TLR expression and carcinogenesis, progression, and clinical prognosis. METHODS: The expression profile of TLRs derived from UCSC pan-cancer data was analysed in multiple dimensions, including clinical analysis, immunological subtype analysis, tumour microenvironment (TME) analysis, tumour stem cell correlation analysis, and drug sensitivity analysis. Additionally, we analyse protein-protein interactions, functional enrichment, and chromatin accessibility, as well as TLR expression in single-cell sequencing data. RESULTS: Our multi-omics analysis results imply that TLRs may operate as a biological marker for carcinogenesis and progression, a potential target for anti-tumour therapy, and a prognostic biomarker, laying the theoretical groundwork for future translational medicine research. CONCLUSION: TLRs are involved in the formation of malignancies and can be explored in further detail as potential prognostic indicators. Key MessagesToll-like receptors (TLRs) are key factors in the process of the innate and adaptive immune response, and their aberrant expression of TLRs have been widely reported in various cancer. However, the association between TLRs stimulation and tumorigenesis of cancer has not been well clarified.In this study, in the pan-cancer data, integrated TLR family gene expression analysis, clinical correlation analysis, immune subtype correlation analysis, tumour microenvironment correlation analysis, tumour stem cell correlation analysis, and drug sensitivity correlation analysis were performed.TLRs play an important role in the development of tumours and can be studied in depth as potential prognostic markers.

Tandem catalytic methylation of naphthalene using CO2 and H2.

We report here the direct methylation of naphthalene using CO2 and H2, which is distinctly more effective than the counterpart methylation with methanol. Benefiting from well-balanced specific rates for CO2-to-methanol conversion over ZnZrOx and the subsequent methylation over H-Beta, significantly enhanced selectivity (93.7%) to monomethylnaphthalenes was achieved.

[Clinical Significance of Application of Comprehensive Management of Atrial Fibrillation].

OBJECTIVE: To improve the accuracy of detection of arrhythmia in patients with atrial fibrillation (AF) and to enable the scientific management and assessment of AF, a comprehensive management tool for AF is proposed, which is helpful for medical staff to systematically evaluate and manage patients with AF. METHODS: A professional view of atrial fibrillation (AF View) was designed to unify the statistical information of AF event, and display the statistical distribution data of AF events and trend data of other physiological parameters or characteristics such as heart rate, blood pressure and ST value during the patient monitoring period in a centralized manner. A multi-dimensional summary information was obtained from AF View. In addition, the monitoring period and monitoring parameters or characteristics in the AF View can be adjusted so as to obtain the summary information under different periods and parameters or characteristics, and get the condition of AF of the patient. RESULTS: Accurate detection and comprehensive management of AF were achieved. CONCLUSIONS: The application of AF comprehensive management proposed in this study is helpful for medical staff to know the condition of AF patients in real time and adjust the treatment plan in time.

[Review of Physiological Parameters Monitoring Technology in the ICU].

Physiological parameters monitoring is essential to direct medical staff to evaluate, diagnose and treat critical patients quantitatively. ECG, blood pressure, SpO2, respiratory rate and body temperature are the basic vital signs of patients in the ICU. The measuring methods are relatively mature at present, and the trend is to be wireless and more accurate and comfortable. Hemodynamics, oxygen metabolism and microcirculation should be taken seriously during the treatment of acute critical patients. The related monitoring technology has made significant progress in recent years, the trend is to reduce the trauma and improve the accuracy and usability. With the development of machine vision and data fusion technology, the identification of patient behavior and deterioration has become hot topics. This review is focused on current parameters monitoring technologies, aims to provide reference for future related research.

Intercellular transport of Tau protein and ß-amyloid mediated by tunneling nanotubes.

Tunneling nanotubes (TNTs) are thin channel-like structures connecting distant cells, providing a route for intercellular communication. In this study, we investigated the physical properties, including the cytoskeletal components, length and diameter, of the TNTs formed by HEK293T, U87 MG, and U251 cell lines. We found that organelles such as lysosomes, mitochondria, and Golgi bodies can be transported through TNTs, indicating that TNTs can mediate material transport. Moreover, we investigated the transport of the Tau protein and ß-amyloid (Aß), which are both closely related to Alzheimer's disease (AD) pathology, through TNTs. The results showed that TNTs formed by various neuronal cell lines can mediate the transport of different forms of the Tau protein and fluorescently labeled Aß and that this transport is bidirectional, with different velocities in various cell lines. Our results confirmed the transport of the Tau protein and Aß between cells and provided a possible explanation for the cascade of cell death in specific brain regions during the progression of AD. Our findings suggest new possibilities for the treatment of AD.

[Research on Patient Monitoring Alarms in ICU and NICU].

OBJECTIVE: The patient monitors were used to explore the alarm actuality in a ICU and NICU to investigate the awareness and reaction of medical staff to alarms. METHODS: A series of surveys and interviews were taken to acquire clinicians' feelings and attitudes to monitoring alarms. The researchers were scheduled to track the alarms with annotations, and collect the alarm data of patient monitors using central monitoring system. RESULTS: A total of 235 387 and 67 783 alarms occurred in ICU and NICU respectively. The average alarm rate was about 142 alarms/patient-day in ICU and 96 alarms/patient-day in NICU. CONCLUSIONS: There remains alarm fatigue in ICU and NICU, the main reason is the large number of false alarms and clinically irrelevant alarms. In addition, patient monitor is still in the level of threshold alarms or combined alarms, the data integrity and intelligence level need to be improved in future.

5-HT6R null mutatrion induces synaptic and cognitive defects.

Serotonin 6 receptor (5-HT6R) is a promising target for a variety of human diseases, such as Alzheimer's disease (AD) and schizophrenia. However, the detailed mechanism underlying 5-HT6R activity in the central nervous system (CNS) is not fully understood. In the present study, 5-HT6R null mutant (5-HT6R-/- ) mice were found to exhibit cognitive deficiencies and abnormal anxiety levels. 5-HT6R is considered to be specifically localized on the primary cilia. We found that the loss of 5-HT6R affected the Sonic Hedgehog signaling pathway in the primary cilia. 5-HT6R-/- mice showed remarkable alterations in neuronal morphology, including dendrite complexity and axon initial segment morphology. Neurons lacking 5-HT6R exhibited increased neuronal excitability. Our findings highlight the complexity of 5-HT6R functions in the primary ciliary and neuronal physiology, supporting the theory that this receptor modulates neuronal morphology and transmission, and contributes to cognitive deficits in a variety of human diseases, such as AD, schizophrenia, and ciliopathies.

Silver-amplified fluorescence immunoassay via aggregation-induced emission for detection of disease biomarker.

Development of simple, robust, and reliable detection strategy of disease biomarkers holds tremendous promise for early clinical diagnosis and prognosis of diseases. In this work, through combining a silver nanoparticle (AgNP) linked immunoassay and aggregation induced emission (AIE)-based fluorogenic Ag+ probe, we developed a silver-amplified fluorescence immunoassay for the detection of disease biomarkers. This method overcame the intrinsic limitations of enzymes as the dissolution of AgNPs generated numerous Ag+, which could switch on the fluorogenic Ag+ probe driven by tetrazolate-Ag+ complexation. As a proof of concept, our method could be used for determining α-fetoprotein (AFP) with a linear relationship in concentrations ranging from 0.1 ng mL-1 to 5 µg mL-1 and a low limit of detection of 42 pg mL-1. Our method was successfully confirmed for the detection of AFP in real serum samples from hepatocellular carcinoma (HCC) patients, demonstrating the great potential for clinical diagnosis.

[Research of Methods to Reduce Alarm Fatigue of Monitoring System].

OBJECTIVE: In order to solve alarm fatigue, the algorithm optimization strategies were researched to reduce false and worthless alarms. METHODS: A four-lead arrhythmia analysis algorithm, a multiparameter fusion analysis algorithm, an intelligent threshold reminder, a refractory period delay technique were proposed and tested with collected 28 679 alarms in multi-center study. RESULTS: The sampling survey indicate that the 80.8% of arrhythmia false alarms were reduced by the four-lead analysis, the 55.9% of arrhythmia and pulse false alarms were reduced by the multi-parameter fusion analysis, the 28.0% and 29.8% of clinical worthless alarms were reduced by the intelligent threshold and refractory period delay techniques respectively. Finally, the total quantity of alarms decreased to 12 724. CONCLUSIONS: To increase the dimensionality of parametric analysis and control the alarm limits and delay time are conducive to reduce alarm fatigue in intensive care units.

The Role of Peroxisome Proliferator-Activated Receptors (PPARs) in Pan-Cancer.

Peroxisome proliferator-activated receptors (PPARs) are members of nuclear transcription factors. The functions of the PPAR family (PPARA, PPARD, and PPARG) and their coactivators (PPARGC1A and PPARGC1B) in maintenance of lipid and glucose homeostasis have been unveiled. However, the roles of PPARs in cancer development remain elusive. In this work, we made use of 11,057 samples across 33 TCGA tumor types to analyze the relationship between PPAR transcriptional expression and tumorigenesis as well as drug sensitivity. We performed multidimensional analyses on PPARA, PPARG, PPARD, PPARGC1A, and PPARGC1B, including differential expression analysis in pan-cancer, immune subtype analysis, clinical analysis, tumor purity analysis, stemness correlation analysis, and drug responses. PPARs and their coactivators expressed differently in different types of cancers, in different immune subtypes. This analysis reveals various expression patterns of the PPAR family at a level of pan-cancer and provides new clues for the therapeutic strategies of cancer.

Nitrogen-Doped Hierarchical Porous Carbon-Promoted Adsorption of Anthraquinone for Long-Life Organic Batteries.

Organic quinone molecules are attractive electrochemical energy storage devices because of their high abundance, multielectron reactions, and structural diversity compared with transition metal-oxide electrode materials. However, they have problems like poor cycle stability and low rate performance on account of the inherent low conductivity and high solubility in the electrolyte. Solving these two key problems at the same time can be challenging. Herein, we demonstrate that using a nitrogen-doped hierarchical porous carbon (NC) with mixed microporous/low-range mesoporous can greatly alleviate the shuttle effect caused by the dissolution of organic molecules in the electrolyte through physical binding and chemisorption, thereby improving the electrochemical performances. Lithium-ion batteries based on the anthraquinone (AQ) electrode exhibit dramatic capacity decay (5.7% capacity retention at 0.2 C after 1000 cycles) and poor rate performance (14.2 mA h g-1 at 2 C). However, the lithium-ion battery based on the NC@AQ cathode shows excellent cycle stability (60.5% capacity retention at 0.2 C after 1000 cycles, 82.8% capacity retention at 0.5 C after 1000 cycles), superior rate capability (152.9 mA h g-1 at 2 C), and outstanding energy efficiency (98% at 0.2 C). Our work offers a new approach to realize the next-generation organic batteries for long life and high rate performance.