Baseline oxygen consumption decreases with cortical depth.

The cerebral cortex is organized in cortical layers that differ in their cellular density, composition, and wiring. Cortical laminar architecture is also readily revealed by staining for cytochrome oxidase-the last enzyme in the respiratory electron transport chain located in the inner mitochondrial membrane. It has been hypothesized that a high-density band of cytochrome oxidase in cortical layer IV reflects higher oxygen consumption under baseline (unstimulated) conditions. Here, we tested the above hypothesis using direct measurements of the partial pressure of O2 (pO2) in cortical tissue by means of 2-photon phosphorescence lifetime microscopy (2PLM). We revisited our previously developed method for extraction of the cerebral metabolic rate of O2 (CMRO2) based on 2-photon pO2 measurements around diving arterioles and applied this method to estimate baseline CMRO2 in awake mice across cortical layers. To our surprise, our results revealed a decrease in baseline CMRO2 from layer I to layer IV. This decrease of CMRO2 with cortical depth was paralleled by an increase in tissue oxygenation. Higher baseline oxygenation and cytochrome density in layer IV may serve as an O2 reserve during surges of neuronal activity or certain metabolically active brain states rather than reflecting baseline energy needs. Our study provides to our knowledge the first quantification of microscopically resolved CMRO2 across cortical layers as a step towards better understanding of brain energy metabolism.

Ultrafast protein digestion using an immobilized enzyme reactor following high-resolution mass spectrometry analysis for rapid identification of abrin toxin.

Abrin toxin, highly dangerous with an estimated human lethal dose of 0.1-1 µg per kg body weight, has attracted much attention regarding criminal and terroristic misuse over the past decade. Therefore, developing a rapid detection method for abrin toxin is of great significance in the field of biosecurity. In this study, based on the specific dissociation method of an immobilized enzyme reactor, the trypsin immobilized reactor Fe3O4@CTS-GA-Try was prepared to replace free trypsin, and the immobilized enzyme digestion process was systematically investigated and optimized by using bovine serum albumin as the simulant of abrin. After 5 min one-step denaturation and reduction, a satisfactory peptide number and coverage were yielded with only 15 s assisted by an ultrasound probe to identify model proteins. Subsequently, abrin was rapidly digested using the established method, resulting in a stable and highly reproducible characteristic peptide number of 39, which can be analyzed by nanoelectrospray ionization coupled with high-resolution mass spectrometry. With the acquisition mode of full MS scan coupled with PRM, not only MS spectroscopy of total abrin peptides but also the corresponding MS/MS spectroscopy of specific abrin peptides can achieve the characteristic detection of abrin toxin and its different isoforms in less than 10 minutes, with high repeatability. This assay provides a universal platform and has great potential for the development of on-site detection and rapid mass spectrometric analysis techniques for macromolecular protein toxins and can further be applied to the integrated detection of chemical and biological agents.

Clinical Approach to Inconclusive Subscapularis Tear Diagnosis: a Meta-analysis.

To identify factors associated with subscapularis (SSC) tears and provide a theoretical basis for clinical diagnosis, we included studies related to subscapularis tears published before February 1, 2023. We screened for six predictors across previous studies for the meta-analysis. The predictors included age, sex, coracoid overlap (CO), coracohumeral distance (CHD), impairment of the long head of the biceps tendon (LHB), and dominant arm. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the studies. The risk ratios (RRs) and the weighted mean differences (WMDs) were used to evaluate the effect size of categorical variables and continuous variables, respectively. The Egger test was used to assess the publication bias of the studies. Ten studies were included from seven countries. A total of 2 126 patients were enrolled, of whom 1 041 had subscapularis tears and 1 085 did not. The study showed that age (WMD, 4.23 [95% CI, 2.32-6.15]; P<.00001), coracoid overlap (WMD, 1.98 [95% CI, 1.55-2.41]; P<.00001), coracohumeral distance(WMD, -1.03 [95% CI, -1.17- -0.88]; P<.00001), and an injury of the long head of the biceps tendon (RR, 4.98 [95% CI, 3.75-6.61]; P<.00001) were risk factors for subscapularis tears. These risk factors can help clinicians identify subscapularis tears early and select appropriate interventions. The level of evidence is 3.

Obese elderly patients with hip fractures may have better survival outcomes after surgery.

BACKGROUND: In recent years, there has been an increasing amount of research on the "obesity paradox". So our primary objective was to explore whether this phenomenon exists in our study, and secondary objective was to determine the effect of body mass index (BMI) on major complications, and the incidence of acute kidney injury (AKI) after hip fracture surgery after controlling for confounding factors. METHODS: We included patients over 70 years old with hip fracture who were admitted to the Department of Orthopedics, Peking University First Hospital between 2015 and 2021. Patients were classified as underweight (UW, < 18.5 kg/m2), normal weight (NW, 18.5-24.9 kg/m2), overweight (OW, 25.0-29.9 kg/m2) and obese (OB, ≥ 30.0 kg/m2). We analyzed demographic characteristics, operation information and postoperative outcomes. Using multivariate regression with normal-weight patients as the reference, we determined the odds of 1-year mortality, major complications, and AKI by BMI category. RESULTS: A total of 644 patients were included. Nine percent of patients died after 1 year, 18% had major postoperative complications, and 12% had AKI. There was a U-shaped relationship between BMI and the rates of major complications or AKI. However, there was a linear decreasing relationship between 1-year mortality and BMI. After controlling for confounding factors, multivariate regression analysis showed that the risk of 1-year mortality after surgery was 2.24 times higher in underweight patients than in normal-weight patients (P < 0.05, OR: 2.24, 95% CI 1.14-4.42). Compared with normal-weight patients, underweight patients had a 2.07 times increased risk of major complications (P < 0.05, OR 2.07, 95% CI 1.21-3.55), and the risk of major complications in obese patients was 2.57 times higher than that in normal-weight patients (P < 0.05, OR 2.57, 95% CI 1.09-6.09). Compared with normal-weight, underweight patients had a 2.18 times increased risk of AKI (P < 0.05, OR 2.18, 95% CI 1.17-4.05). CONCLUSIONS: The 1-year mortality risk of patients with higher BMI was significantly reduced. Besides, compared with normal-weight patients, underweight patients and obese patients have a higher risk of major complications; low-weight and obese patients are at higher risk for AKI.

Strong Electron Coupling of Ru and Vacancy-Rich Carbon Dots for Synergistically Enhanced Hydrogen Evolution Reaction.

The exploitation of ingenious strategies to improve the activity and stability of ruthenium (Ru) is crucial for the advancement of Ru-based electrocatalysts. Vacancy engineering is a typical strategy for modulating the catalytic activity of electrocatalysts. However, creating vacancies directly into pure metallic Ru is difficult because of the extremely stringent conditions required and will result in instability because the integrity of the crystal structure is destroyed. In response, a compromise tactic by introducing vacancies in a Ru composite structure is proposed, and vacancy-rich carbon dots coupled with Ru (Ru@CDs) are elaborately constructed. Specifically, the vacancy-rich carbon dots (CDs) serve as an excellent platform for anchoring and trapping Ru nanoparticles, thus restraining their agglomeration and growth. As expected, Ru@CDs exhibited excellent catalytic performance with a low overpotential of 30 mV at 10 mA cm-2 in 1 m KOH, a small Tafel slope of 22 mV decade-1 , and robust stability even after 10 000 cycles. The low overpotential is comparable to those of most previously reported Ru-based electrocatalysts. Additionally, spectroscopic characterizations and theoretical calculations demonstrate that the rich vacancies and the electron interactions between Ru and CDs synergistically lower the intermediate energy barrier and thereby maximize the activity of the Ru@CDs electrocatalyst.

Rapid detection of sulfur mustard hydrolysis products based on microextraction by packed sorbent combined with nano-electrospray ionization mass spectrometry.

RATIONALE: Sulfur mustard is a blister agent prohibited by the Chemical Weapons Convention, and the detection of its hydrolysis product, thiodiglycol (TDG), is an important indicator of blister agent contamination. Due to the poor volatility and low extraction efficiency of TDG, derivatization gas chromatography or liquid chromatography is required for conventional methods, and the detection process is cumbersome and time-consuming. METHODS: A microextraction by packed sorbent (MEPS) device and a nano-electrospray ionization (nano-ESI) device were used. The central composite design (CCD) model of Response Surface Methodology was used to optimize the elution procedure; the variance analysis under equal repeated trials with multiple factors was used to quantitatively analyze the significance of the impact of related factors on the nano-ESI efficiency. The MEPS-nano-ESI-MS experimental conditions were optimized. RESULTS: A new detection method of sulfur mustard hydrolysis products in water based on MEPS-nano-ESI-MS was established; the detection limit was 1 ng/mL and was linear between 5 ng/mL and 100 ng/mL (R2 = 0.9911) with a precision of ≤7.2%, and the recovery rate was 107.89% when the sample concentration was 40 ng/mL. CONCLUSIONS: The experimental results showed that the proposed method could quickly detect the contaminated water samples without chromatographic separation and derivatization, thereby verifying the contamination of sulfur mustard on site.

Comparison of azithromycin and erythromycin in the treatment of mycoplasma pneumonia in children.

OBJECTIVE: To study and compare the clinical effects of azithromycin and erythromycin on children with mycoplasma pneumonia. METHODS: Total 132 children with mycoplasma pneumonia who were admitted to our hospital between November 2017 and September 2018 were selected as the research subjects. All the children were divided into an observation group and a control group according to random number table, 66 each. The observation group was treated with azithromycin, while the control group was treated with erythromycin. The therapeutic effect, incidence of adverse reactions and disappearance time of clinical symptoms were compared between the two groups. RESULTS: The total efficacy of the observation group was 98.04%, and that of the control group was 74.51%; there was a significant difference (X2=7.184, P=0.007). The incidence of adverse reactions in the observation group was 15.69%, significantly lower than that in the control group (41.18%) (X2=6.376, P=0.002). The disappearance of fever, cough, rale and X ray shadow of the observation group was significantly earlier than that of the control group, and the difference was statistically significant (P<0.05). CONCLUSION: Compared with erythromycin, azithromycin is more effective in the treatment of mycoplasma pneumonia in children. Azithromycin can further shorten the improvement time of clinical symptoms and signs and has few adverse reactions and high safety. It is worth clinical application.

Designed Formation of Hybrid Nanobox Composed of Carbon Sheathed CoSe2 Anchored on Nitrogen-Doped Carbon Skeleton as Ultrastable Anode for Sodium-Ion Batteries.

Research on sodium-ion batteries (SIBs) has recently been revitalized due to the unique features of much lower costs and comparable energy/power density to lithium-ion batteries (LIBs), which holds great potential for grid-level energy storage systems. Transition metal dichalcogenides (TMDCs) are considered as promising anode candidates for SIBs with high theoretical capacity, while their intrinsic low electrical conductivity and large volume expansion upon Na+ intercalation raise the challenging issues of poor cycle stability and inferior rate performance. Herein, the designed formation of hybrid nanoboxes composed of carbon-protected CoSe2 nanoparticles anchored on nitrogen-doped carbon hollow skeletons (denoted as CoSe2 @C∩NC) via a template-assisted refluxing process followed by conventional selenization treatment is reported, which exhibits tremendously enhanced electrochemical performance when applied as the anode for SIBs. Specifically, it can deliver a high reversible specific capacity of 324 mAh g-1 at current density of 0.1 A g-1 after 200 cycles and exhibit outstanding high rate cycling stability at the rate of 5 A g-1 over 2000 cycles. This work provides a rational strategy for the design of advanced hybrid nanostructures as anode candidates for SIBs, which could push forward the development of high energy and low cost energy storage devices.

Tough Magnetic Chitosan Hydrogel Nanocomposites for Remotely Stimulated Drug Release.

As one of important biomaterials for localized drug delivery system, chitosan hydrogel still suffer several challenges, including poor mechanical properties, passive drug release behavior and lack of remote stimuli response. To address these challenges, a facile in situ hybridization method was reported for fabricate tough magnetic chitosan hydrogel (MCH), which remotely switched drug release from passive release to pulsatile release under a low frequency alternating magnetic field (LAMF). The in situ hybridization method avoided the aggregation of magnetic nanoparticles (MNPs) in hydrogel, which simultaneously brings 416% and 265% increase in strength and elastic modulus, respectively. The mechanical property enhancement was contributed by the physical crosslinking of in situ synthesized MNPs. When a LAMF with 15 min ON-15 min OFF cycles was applied to MCH, the fraction release showed zigzag shape and pulsatile release behavior with quick response. The cumulative release and fraction release of drug from MCH were improved by 67.2% and 31.9%, respectively. MTT results and cell morphology indicated that the MCH have excellent biocompatibility and no acute adverse effect on MG-63 cells. The developed tough MCH system holds great potential for applications in smart drug release system with noninvasive characteristics and magnetic field stimulated drug release behavior.

Budesonide Nebulization in the Treatment of Neonatal Ventilator Associated Pneumonia.

OBJECTIVE: To investigate the clinical effect of budesonide nebulization in the treatment of ventilator associated pneumonia of newborns and its safety. METHODS: Forty-five newborns who had ventilator associated pneumonia and were admitted into the Binzhou People's Hospital between May 2014 and May 2015 were selected and included as an observation group. Moreover, another forty-five newborns who had ventilator associated pneumonia but did not undergo budesonide treatment in 2014 were randomly selected and included as a control group. Patients in the observation group were given budesonide suspension nebulization in addition to the conventional treatment. The evaluation indicators for therapeutic effect were compared between the two groups. The changes of head circumference, height and weight and death rate were observed by follow up after treatment. RESULTS: The mechanical ventilation time, time for recovering from chest X-ray scan and hospitalization time of patients in the observation group were shorter than that of the control group, and the difference had statistical significance (P<0.05). The oxygen index of the patients in the observation group was significantly improved compared to that of the control group, and the difference had statistical significance (P<0.05). Patients in the two groups were followed up for six months after discharge. The head circumference, height and weight of the patients in the observation group in the 3rd and 6th month were compared to those of the control group, suggesting no significant differences (P>0.05). The cumulative death rate of the observation group in the 6th month after treatment was significantly lower than that of the control group, and the difference had statistical significance (P<0.05). CONCLUSION: Treating ventilator associated pneumonia of newborns with budesonide nebulization can effectively shorten mechanical ventilation time, time for recovering from chest X-ray scan and hospitalization time, improve pulmonary diffusion function and reduce the death rate, without affecting the growth and development of patients in the future.

A novel asymmetrical arc-shaped electrode ion trap for improving the performance of a miniature mass spectrometer.

RATIONALE: The pivotal challenge associated with miniature mass analyzers is their proper design and construction without sacrificing performance. In order to analyze and improve the performance of a miniature linear ion trap with odd and even multipole fields, we designed a novel asymmetrical arc-shaped electrode ion trap (AAEIT), and tested the properties of AAEITs with different dimensions. METHODS: A series of asymmetrical ion traps using arc-shaped electrodes were designed to optimize the properties (resolutions and intensity) of the coupling effects between odd and even multipole fields. Using arginine and reserpine, we evaluated the performance of mass resolution, ion intensity ratio and deduced the collision-induced dissociation (CID) efficiency using a self-constructed electrospray ionization mass spectrometry (ESI-MS) platform. RESULTS: An AAEIT with field radius dimensions of 5 mm × 5.75 mm exhibits a good performance: its maximum resolution of 833 (FWHM) at m/z 175 was achieved for the side of small electrode. With this AAEIT, a tandem mass (MS/MS) capability with 91.0% CID efficiency was obtained with reserpine (m/z 609). CONCLUSIONS: The results indicated that the AAEIT, comprising both odd and even multipole fields, could act as a qualified linear ion trap mass analyzer with compact structure, high resolution, and high tandem mass analysis efficiency. It has a great potential in miniature mass spectrometry.

Osseointegration of bioactive microarc oxidized amorphous phase/TiO2 nanocrystals composited coatings on titanium after implantation into rabbit tibia.

The amorphous phase/TiO2 nanocrystals (APTN) composited coatings were prepared on Ti implants for biomedical applications. The Ti implants without and with the APTN composited coatings both do not cause any adverse effects after implantation into the rabbit tibia. The osseointegration of Ti implants after covering the APTN coatings is improved pronouncedly, greatly increasing the interface bonding strength between the implants and newly formed bones. In addition, it is interesting that the newly formed bone tissues appear in the micro-pores of the APTN coatings, promoting the interface bonding between the implants and new bones by the mechanical interlock. Moreover, the Ti implant with the APTN coatings formed at higher applied voltage exhibit higher shear strength and displacement during the pushing out experiment probably due to its better osseointegration.

Accurate Detection of G-Series Agent Simulants by Pseudo-Multiple Reaction Monitoring on Miniature LIT-MS.

Rapid and accurate on-site detection of chemical warfare agents (CWAs) could defend military and civilian populations against current and emerging chemical weapons. With the development of ambient ionization and linear ion trap technology, the rapid and accurate quantitative determination method of CWAs based on direct ionization and multistage mass spectrometry has attracted widespread attention. In this study, a microliter electrospray ionization-miniature linear ion trap mass spectrometry (LIT-MS) instrument was designed and constructed, and the effects of quadrupole enhanced dipole resonance excitation on the resolution and sensitivity were investigated; consequently, the parameters of CWAs detection were optimized. Based on the broad time-frequency ion excitation technology, accurate multiple reaction monitoring (MRM) quantitative analysis of DMMP (G-series agent simulants, m/z 125 → m/z 93) was obtained. The linear correlation coefficient in the concentration range of 1 to 20 µg/mL could reach 99.02%, and the relative standard deviations (RSD) of continuous repeatability, interday repeatability, and intraday repeatability were all less than 10%. The results showed that the accurate pseudo-MRM detection method based on miniature linear ion trap mass spectrometry for CWAs detection was feasible.

Precycling Strategy in Suitable Voltage to Improve the Stability of Interfacial Film and Suppress the Decline of LiNi0.6Mn0.2Co0.2O2 Cathode at Elevated Temperatures.

Layered ternary oxide LiNixMnyCo1-x-yO2 is a promising cathode candidate for high-energy lithium-ion batteries (LIBs). However, the capacity of LIBs is significantly restricted by several factors, including the repeated dissolution-regeneration of the interfacial film at high temperatures, the dissolution of transition metals, and the increase of impedance. Herein, a new precycling strategy in suitable voltage scope at room temperature is proposed to construct a uniform, thermally stable, and insoluble cathode-electrolyte interface (CEI), which helps to maintain stable cycling performances at high temperatures. Specifically, after 5 precycles in the range of 3.85-4.3 V at room temperature, a CEI layer containing numerous inorganic components and oligomers is formed on the surface of LiNi0.6Mn0.2Co0.2O2. Subsequently, the harmful side reactions are effectively suppressed, endowing the cell with an excellent capacity retention of 84.67% after 50 cycles at 0.5C and 55 °C, much higher than that of 65.61% under the conventional film-forming process conditions. This work emphasizes the crucial role of the precycling strategy in regulating the characteristics of CEI layer on the surface of cathode electrode, opening up a new avenue for the high-temperature application of positive electrodes of LIBs.

Insights into the effects of coating and single crystallization on the rate performance and cycle life of LiNi0.9Mn0.1O2 cathode.

Coating and single crystal are two common strategies for cobalt-free nickel-rich layered oxides to solve its poor rate performance and cycle stability. However, the action mechanism of different modification protocols to suppress the attenuation are unclear yet. Herein, the Li2MoO4 layer-coated polycrystalline LiNi0.9Mn0.1O2 (1.0 %-Mo + NM91) and single crystal LiNi0.9Mn0.1O2 (SC-NM91) are prepared to investigate this difference, respectively. By focusing on the interior of particles, the relationship between structure evolution and electrochemical behavior is systematically studied, and the intrinsic mechanism of coating/single-crystallization modifications on suppressing the attenuation is clarified. The results show that microcracks in LiNi0.9Mn0.1O2 (NM91) are the main culprit leading to the rate capability decay, and the coating can effectively prevent the radial diffusion of microcracks from the center to surface, inhibiting the generation of surface side reactions. Therefore, the coating has a more advantage in improving the rate performance at 5.0C, the discharge capacity of 1.0 %-Mo + NM91 (130.6 mAh/g) is 7.9 % higher than that of SC-NM91 (121.0 mAh/g). In contrast, the single-crystallization can effectively prevent the formation of intergranular cracks arising from the anisotropic stress in NM91, which causes the severe cycle degradation. Correspondingly, the grain boundary-free SC-NM91 shows superior cyclability. The capacity retention rate of SC-NM91 (80.8 %) at 0.2C after 100cycles is 6.3 % higher than that of 1.0 %-Mo + NM91 (74.5 %). This work concludes the effect difference of different modification methods on enhancing the electrochemical performance, which provides theoretical and technical guidance for the optimized and targeted modification design in the cobalt-free high nickel cathode materials.

Electrical Responsive Coating with a Multilayered TiO2-SnO2-RuO2 Heterostructure on Ti for Controlling Antibacterial Ability and Improving Osseointegration.

The bacterial infection and poor osseointegration of Ti implants could significantly compromise their applications in bone repair and replacement. Based on the carrier separation ability of the heterojunction and the redox reaction of pseudocapacitive metal oxides, we report an electrically responsive TiO2-SnO2-RuO2 coating with a multilayered heterostructure on a Ti implant. Owing to the band gap structure of the TiO2-SnO2-RuO2 coating, electron carriers are easily enriched at the coating surface, enabling a response to the endogenous electrical stimulation of the bone. With the formation of SnO2-RuO2 pseudocapacitance on the modified surface, the postcharging mode can significantly change the surface chemical state of the coating due to the redox reaction, enhancing the antibacterial ability and osteogenesis-related gene expression of the human bone marrow mesenchymal stem cells. Owing to the attraction for Ca2+, only the negatively postcharged SnO2@RuO2 can promote apatite deposition. The in vivo experiment reveals that the S-SnO2@RuO2-NP could effectively kill the bacteria colonized on the surface and promote osseointegration with the synostosis bonding interface. Thus, negatively charging the electrically responsive coating of TiO2-SnO2-RuO2 is a good strategy to endow modified Ti implants with excellent antibacterial ability and osseointegration.

Discovery of FeP/Carbon Dots Nanozymes for Enhanced Peroxidase-Like Catalytic and Antibacterial Activity.

Iron phosphide/carbon (FeP/C) serving as electrocatalysts exhibit excellent activity in oxygen reduction reaction (ORR) process. H2O2 catalyzed by peroxidase (POD) is similar to the formation of new electron transfer channels and the optimization of adsorption of oxygen-containing intermediates or desorption of products in ORR process. However, it is still a challenge to discover FeP/C with enhanced POD-like catalytic activity in the electrocatalytic database for biocatalysis. The discovery of FeP/carbon dots (FeP/CDs) nanozymes driven by electrocatalytic activity for enhanced POD-like ability is demonstrated. FeP/CDs derived from CDs-Fe3+ chelates show enhanced POD-like catalytic and antibacterial activity. FeP/CDs exhibit enhanced POD-like activities with a specific activity of 31.1 U mg-1 that is double higher than that of FeP. The antibacterial ability of FeP/CDs nanozymes with enhanced POD-like activity is 98.1%. The antibacterial rate of FeP/CDs nanozymes (250 µg mL-1) increased by 5%, 15%, and 36% compared with FeP, Fe2O3/CDs, and Cu3P/CDs nanozymes, respectively. FeP/CDs nanozymes will attract more efforts to discover or screen transition metal phosphide/C nanozymes with enhanced POD-like catalytic activity for biocatalysis in the electrocatalytic database.

Rapamycin functionalized carbon Dots: Target-oriented synthesis and suppression of vascular cell senescence.

Suppression of vascular cell senescence is of great significance in preventing cardiovascular diseases such as hypertension and atherosclerosis. The oxidative stress damage caused by reactive oxygen species (ROS) can lead to cellular senescence. Rapamycin (Rapa) is well known to suppress cell senescence via mammalian target of rapamycin (mTOR) pathway. However, poor water solubility and lack of ROS scavenging ability limit the further development of Rapa. To improve the solubility of Rapa and endow with ROS scavenging ability, Rapa functionalized carbon dots (Rapa-CDs) are target-oriented synthesized via free radical polymerization combination with hydrothermal carbonization. Rapa-CDs improve the solubility of Rapa and show ROS scavenging abilities. The solubility of Rapa-CDs with 9.41 g is improved 3.6 × 104 times higher than that of Rapa (2.6 × 10-4 g). The half maximal inhibitory concentration (IC50) of Rapa-CDs toward hydroxyl radical (•OH) and 2,2-Diphenyl-1-picrylhydrazyl free radical (DPPH•) are 0.18 and 0.17 mg/mL, respectively. Rapa-CDs show anti-oxidative stress effect in HEVECs (Human Umbilical Vein Endothelial Cells) via reducing ROS levels by 87 %. Rapa-CDs alleviate HUVECs senescence by suppressing mTOR overactivation, attenuate the expression of P53, P21 and P16. The study demonstrates the target-oriented synthesis of drugs functionalized CDs with anti-senescence via dual-pathway of anti-oxidative stress and mTOR.

Target-Oriented Synthesis of Triphenylphosphine Functionalized Carbon Dots with Negative Charge for ROS Scavenging and Mitochondrial Targeting.

Triphenylphosphine functionalized carbon dots (TPP-CDs) showcase robust mitochondria targeting capacity owing to their positive electrical properties. However, TPP-CDs typically involve complicated synthesis steps and time-consuming postmodification procedures. Especially, the one-step target-oriented synthesis of TPP-CDs and the regulation of TPP linkage modes remain challenges. Herein, we propose a free-radical-initiated random copolymerization in combination with hydrothermal carbonation to regulate the TPP backbone linkage for target-oriented synthesis of triphenylphosphine copolymerization carbon dots (TPPcopoly-CDs). The linkage mechanism of random copolymerization reactions is directional, straightforward, and controllable. The TPP content and IC50 of hydroxyl radicals scavenging ability of TPPcopoly-CDs are 53 wt % and 0.52 mg/mL, respectively. TPP serves as a charge control agent to elevate the negatively charged CDs by 20 mV. TPPcopoly-CDs with negative charge can target mitochondria, and in the corresponding mechanism the TPP moiety plays a crucial role in targeting mitochondria. This discovery provides a new perspective on the controlled synthesis, TPP linkage modes, and mitochondrial targeting design of TPP-CDs.

Chitosan-Rapamycin Carbon Dots Alleviate Glaucomatous Retinal Injury by Inducing Autophagy to Promote M2 Microglial Polarization.

Introduction: Glaucoma is a prevalent cause of irreversible vision impairment, characterized by progressive retinal ganglion cells (RGCs) loss, with no currently available effective treatment. Rapamycin (RAPA), an autophagy inducer, has been reported to treat glaucoma in rodent models by promoting RGC survival, but its limited water solubility, systemic toxicity, and pre-treatment requirements hinder its potential clinical applications. Methods: Chitosan (CS)-RAPA carbon dot (CRCD) was synthesized via hydrothermal carbonization of CS and RAPA and characterized by transmission electron microscopy, Fourier transform infrared spectra, and proton nuclear magnetic resonance. In vitro assays on human umbilical cord vein endothelial and rat retinal cell line examined its biocompatibility and anti-oxidative capabilities, while lipopolysaccharide-stimulated murine microglia (BV2) assays measured its effects on microglial polarization. In vivo, using a mouse retinal ischemia/reperfusion (I/R) model by acute intraocular pressure elevation, the effects of CRCD on visual function, RGC apoptosis, oxidative stress, and M2 microglial polarization were examined. Results: CRCD exhibited good water solubility and anti-oxidative capabilities, in the form of free radical scavenging. In vitro, CRCD was bio-compatible and lowered oxidative stress, which was also found in vivo in the retinal I/R model. Additionally, both in vitro with lipopolysaccharide-stimulated BV2 cells and in vivo with the I/R model, CRCD was able to promote M2 microglial polarization by activating autophagy, which, in turn, down-regulated pro-inflammatory cytokines, such as IL-1ß and TNF-α, as well as up-regulated anti-inflammatory cytokines, such as IL-4 and TGF-ß. All these anti-oxidative and anti-inflammatory effects ultimately aided in preserving RGCs, and subsequently, improved visual function. Discussion: CRCD could serve as a potential novel treatment strategy for glaucoma, via incorporating RAPA into CDs, in turn not only mitigating its toxic side effects but also enhancing its therapeutic efficacy.