Reactive Oxygen Species-Responsive Pillararene-Embedded Covalent Organic Frameworks with Amplified Antimicrobial Photodynamic Therapy for the Targeted Elimination of Periodontitis Pathogens.

Reactive oxygen species (ROS)-responsive drug delivery systems possess immense potential for targeted delivery and controlled release of therapeutics. However, the rapid responsiveness to ROS and sustained release of antibacterial drugs are often limited by the challenging microenvironment of periodontitis. Integrating ROS-responsive drug delivery systems with photocatalytic technologies presents a strategic approach to overcome these limitations. Herein, a pillararene-embedded covalent organic framework (PCOF) incorporating the antibacterial prodrug thioacetal (TA) has been developed to treat periodontitis. This drug-loaded nanoplatform, namely TA-loaded PCOF, utilizes the self-amplifying ROS property to enhance therapeutic efficacy. PCOFs demonstrate exceptional photosensitivity and ROS generation capabilities when employed as drug carriers. When exposed to ROS, TA within the nanoplatform was activated and cleaved into cinnamaldehyde (CA), a highly potent antibacterial compound. By leveraging visible light to activate the site-specific infection targeting, TA-loaded PCOF effectively alleviated periodontitis, thereby advancing the field of antibacterial drug delivery systems.

Fast Interfacial Defluorination Kinetics Enables Stable Cycling of Low-Temperature Lithium Metal Batteries.

The development of low-temperature lithium metal batteries (LMBs) encounters significant challenges because of severe dendritic lithium growth during the charging/discharging processes. To date, the precise origin of lithium dendrite formation still remains elusive due to the intricate interplay between the highly reactive lithium metal anode and organic electrolytes. Herein, we unveil the critical role of interfacial defluorination kinetics of localized high-concentration electrolytes (LHCEs) in regulating lithium dendrite formation, thereby determining the performance of low-temperature LMBs. We investigate the impact of solvation structures of LHCEs on low-temperature LMBs by employing tetrahydrofuran (THF) and 2-methyltetrahydrofuran (2-MeTHF) as comparative solvents. The combination of comprehensive characterizations and theoretical simulations reveals that the THF-based LHCE featured with a strong solvation strength exhibits fast interfacial defluorination reaction kinetics, thus leading to the formation of an amorphous and inorganic-rich solid-electrolyte interphase (SEI) that can effectively suppress the growth of lithium dendrites. As a result, the highly reversible Li metal anode achieves an exceptional Coulombic efficiency (CE) of up to ∼99.63% at a low temperature of -30 °C, thereby enabling stable cycling of low-temperature LMB full cells. These findings underscore the crucial role of electrolyte interfacial reaction kinetics in shaping SEI formation and provide valuable insights into the fundamental understanding of electrolyte chemistry in LMBs.

Identifying the optimal measurement timing and hemodynamic targets of portal pressure gradient after TIPS in patients with cirrhosis and variceal bleeding.

BACKGROUND & AIMS: The optimal timing of measurement and hemodynamic targets of portacaval pressure gradient (PPG) after transjugular intrahepatic portosystemic shunt (TIPS) placement remain unclear. This study aimed to identify the ideal moment for hemodynamic measurements and the optimal target of PPG in patients undergoing covered TIPS for variceal bleeding. METHODS: Between May 2018 and December 2021, 466 consecutive patients with recurrent variceal bleeding treated with covered TIPS were prospectively included. Post-TIPS PPG was measured immediately (immediate PPG), 24-72 hours (early PPG), and again 1 month (late PPG) after TIPS placement. The agreement among PPGs measured at different time points was assessed by intra-class correlation coefficient (ICC) and Bland-Altman method. The unadjusted and confounder-adjusted effects of PPGs on clinical outcomes (portal hypertensive complications [PHCs], overt hepatic encephalopathy [OHE], further decompensation, and death) were assessed using Fine and Gray competing risk regression models. RESULTS: The agreement between early PPG and late PPG (ICC: 0.34) was better than that between immediate PPG and late PPG (ICC: 0.23, p <0.001). Early PPG revealed an excellent predictive value for PHCs (early PPG≥ vs. <12 mmHg: adjusted hazard ratio 2.17, 95% CI 1.33-3.55, p = 0.002) and OHE (0.40, 95% CI 0.17-0.91, p = 0.030), while immediate PPG did not. Late PPG showed a predictive value for PHC risk but not OHE. By targeting the lowest risk of further decompensation, we identified an optimal hemodynamic target with early PPG ranging from 11 to 14 mmHg that was associated with a decreased risk of OHE and effective prevention of PHC. CONCLUSIONS: PPG measured 24 to 72 hours after TIPS correlates with long-term PPG and clinical outcomes, and a hemodynamic target PPG of 11-14 mmHg is associated with reduced encephalopathy but not compromised clinical efficacy. IMPACT AND IMPLICATIONS: The optimal timing of measurement and hemodynamic targets of portacaval pressure gradient (PPG) after transjugular intrahepatic portosystemic shunt (TIPS) remain unclear. Here we show that post-TIPS PPG measured at least 24 hours but not immediately after the procedure correlated with long-term PPG and clinical events. Thus, PPG measurements taken at least 24 hours after TIPS should be used to guide decision making in order to improve clinical outcomes. Targeting a post-TIPS PPG of 11-14 mmHg or a 20%-50% relative reduction from pre-TIPS baseline measured 24-72 hours after the procedure was associated with reduced encephalopathy but not compromised clinical efficacy. Thus, these criteria could be used to guide TIPS creation and revision in patients with cirrhosis and variceal bleeding undergoing covered TIPS. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, ID: NCT03590288.

Alemtuzumab induction is associated with decreased hospitalization rates in pediatric kidney transplant: A UNOS data review for safety and outcomes with common induction regimens.

BACKGROUND: We hypothesized that alemtuzumab use is safe in pediatric kidney transplant recipients (KTRs) with equivalent long-term outcomes compared to other induction agents. METHODS: Using pediatric kidney transplant recipient data in the UNOS database between January 1, 2000, and June 30, 2022, multivariate logistic regression, multivariable Cox regression, and survival analyses were utilized to estimate the likelihoods of 1st-year and all-time hospitalizations, acute rejection, CMV infection, delayed graft function (DGF), graft loss, and patient mortality among recipients of three common induction regimens (ATG, alemtuzumab, and basiliximab). RESULTS: There were no differences in acute rejection or graft failure among induction or maintenance regimens. Basiliximab was associated with lower odds of DGF in deceased donor recipients (OR 0.77 [0.60-0.99], p = .04). Mortality was increased in patients treated with steroid-containing maintenance (HR 1.3 [1.005-1.7] p = .045). Alemtuzumab induction correlated with less risk of CMV infection than ATG (OR 0.76 [0.59-0.99], p = .039). Steroid-containing maintenance conferred lower rate of PTLD compared to steroid-free maintenance (HR 0.59 [0.4-0.8] p = .001). Alemtuzumab was associated with less risk of hospitalization within 1 year (OR 0.79 [0.67-0.95] p = .012) and 5 years (HR 0.54 [0.46-0.65] p < .001) of transplantation. Steroid maintenance also decreased 5 years hospitalization risk (HR 0.78 [0.69-0.89] p < .001). CONCLUSIONS: Pediatric KTRs may be safely treated with alemtuzumab induction without increased risk of acute rejection, DGF, graft loss, or patient mortality. The decreased risk of CMV infections and lower hospitalization rates compared to other agents make alemtuzumab an attractive choice for induction in pediatric KTRs, especially in those who cannot tolerate ATG.

Willow catkin template synthesis of NiS@NSC hollow tubes for highly sensitive dual-function electrochemical detection of acetaminophen and Cu2.

Public health and environmental well-being have become increasingly threatened by the contamination of pharmaceuticals and heavy metal ions. This study focuses on addressing this critical issue by developing a novel electrochemical sensor for the dual-functional detection of acetaminophen (AP) and Cu2+. Utilizing willow catkins as a biomass template, a hollow tubular NiS@NSC composite was prepared by simple nickel salt impregnation combined with calcination and sulfurization. A highly sensitive dual-functional electrochemical sensor was thus constructed that can detect both acetaminophen (AP) and Cu2+. By examining its electrochemical properties, the sensor achieves an impressive detection limit of 1.33 pM for AP, with a linear range of 4.00 pM ~ 0.15 mM. The sensor can also detect Cu2+, with a detection limit of 1.04 µM, and a linear range of 3.13 µM ~ 0.66 mM. The sensor also exhibits strong resistance to interference, and good repeatability and stability. In addition, the sensor has demonstrated good performance in actual sample analysis, including the detection of AP in serum and Cu2+ in wastewater. This excellent electrochemical sensing performance is mainly attributed to the synergistic effect of its unique tubular structure and highly conductive N, S co-doped carbon. This results in the sensor exhibiting minimal charge transfer resistance, an extensive electrochemically active surface area, and a high density of active sites.

Macrocycle-Strutted Coordination Microparticles for Fluorescence-Monitored Photosensitization and Substrate-Selective Photocatalytic Degradation.

The prosperous advancement of supramolecular chemistry has motivated us to construct supramolecular hybrid materials with integrated functionalities. Herein, we report an innovative type of macrocycle-strutted coordination microparticle (MSCM) using pillararenes as the struts and "pockets", which performs unique activities of fluorescence-monitored photosensitization and substrate-selective photocatalytic degradation. Prepared via a convenient one-step solvothermal method, MSCM showcases the incorporation of supramolecular hybridization and macrocycles, endowed with well-ordered spherical architectures, superior photophysical properties, and photosensitizing capacity, where a self-reporting fluorescence response is exhibited upon photoinduced generation of multiple reactive oxygen species. Importantly, photocatalytic behaviors of MSCM show marked divergence toward three different substrates and reveal pronounced substrate-selective catalytic mechanisms, attributing to the variety in the affinity of substrates toward MSCM surfaces and pillararene cavities. This study brings new insight into the design of supramolecular hybrid systems with integrated properties and further exploration of functional macrocycle-based materials.

Cu-Doped Iron Oxide for the Efficient Electrocatalytic Nitrate Reduction Reaction.

The electrochemical nitrate reduction reaction (NO3RR) is a promising alternative synthetic route for sustainable ammonia (NH3) production, because it not only eliminates nitrate (NO3-) from water but also produces NH3 under mild operating conditions. However, owing to the complicated eight-electron reaction and the competition from the hydrogen evolution reaction, developing catalysts with high activities and Faradaic efficiencies (FEs) is highly imperative to improve the reaction performance. In this study, Cu-doped Fe3O4 flakes are fabricated and demonstrated to be excellent catalysts for electrochemical conversion of NO3- to NH3, with a maximum FE of ∼100% and an NH3 yield of 179.55 ± 16.37 mg h-1 mgcat-1 at -0.6 V vs RHE. Theoretical calculations reveal that doping the catalyst surface with Cu results in a more thermodynamically facile reaction. These results highlight the feasibility of promoting the NO3RR activity using heteroatom doping strategies.

Sub-3 nm Pt@Ru toward Outstanding Hydrogen Oxidation Reaction Performance in Alkaline Media.

Anion-exchange membrane fuel cells (AEMFCs) are promising alternative hydrogen conversion devices. However, the sluggish kinetics of the hydrogen oxidation reaction in alkaline media hinders further development of AEMFCs. As a synthesis method commonly used to prepare disordered PtRu alloys, the impregnation process is ingeniously designed herein to synthesize sub-3 nm Pt@Ru core-shell nanoparticles by sequentially reducing Pt and Ru at different annealing temperatures. This method avoids complex procedures and synthesis conditions for organic synthesis systems, and the atomic structure evolution of the synthesized core-shell nanoparticles can be tracked. The synthesized Pt@Ru electrocatalyst shows an ultrasmall average size of ∼2.5 nm and thereby a large electrochemical surface area (ECSA) of 166.66 m2 gPt+Ru-1. Exchange current densities (j0) normalized to the mass (Pt + Ru) and ECSA of this electrocatalyst are 8.0 and 5.8 times as high as those of commercial Pt/C, respectively. To the best of our knowledge, the achieved mass-normalized j0 measured by rotating disk electrodes is the highest reported so far. The membrane electrode assembly test of the Pt@Ru electrocatalyst shows a peak power density of 1.78 W cm-2 (0.152 mgPt+Ru cmanode-2), which is higher than that of commercial PtRu/C (1.62 W cm-2, 0.211 mgPt+Ru cmanode-2). The improvement of the intrinsic activity can be attributed to the electron transfer from the Ru shell to the Pt core, and the ultrafine particles further enhance the mass activity. This work reveals the feasibility of using simple impregnation to synthesize fine core-shell nanocatalysts and the importance of investigating the atomic structure of PtRu nanoparticles and other disordered alloys.

Revealing Structural Insights of Solid Electrolyte Interphase in High-Concentrated Non-Flammable Electrolyte for Li Metal Batteries by Cryo-TEM.

High-concentrated non-flammable electrolytes (HCNFE) in lithium metal batteries prevent thermal runaway accidents, but the microstructure of their solid electrolyte interphase (SEI) remains largely unexplored, due to the lack of direct imaging tools. Herein, cryo-HRTEM is applied to directly visualize the native state of SEI at the atomic scale. In HCNFE, SEI has a uniform laminated crystalline-amorphous structure that can prevent further reaction between the electrolyte and lithium. The inorganic SEI component, Li2 S2 O7 , is precisely identified by cryo-HRTEM. Density functional theory (DFT) calculations demonstrate that the final Li2 S2 O7 phase has suitable natural transmission channels for Li-ion diffusion and excellent ionic conductivity of 1.2 × 10-5 S cm-1 .

Dark2Light: multi-stage progressive learning model for low-light image enhancement.

Due to severe noise and extremely low illuminance, restoring from low-light images to normal-light images remains challenging. Unpredictable noise can tangle the weak signals, making it difficult for models to learn signals from low-light images, while simply restoring the illumination can lead to noise amplification. To address this dilemma, we propose a multi-stage model that can progressively restore normal-light images from low-light images, namely Dark2Light. Within each stage, We divide the low-light image enhancement (LLIE) into two main problems: (1) illumination enhancement and (2) noise removal. Firstly, we convert the image space from sRGB to linear RGB to ensure that illumination enhancement is approximately linear, and design a contextual transformer block to conduct illumination enhancement in a coarse-to-fine manner. Secondly, a U-Net shaped denoising block is adopted for noise removal. Lastly, we design a dual-supervised attention block to facilitate progressive restoration and feature transfer. Extensive experimental results demonstrate that the proposed Dark2Light outperforms the state-of-the-art LLIE methods both quantitatively and qualitatively.

Na-K Alloy Anode for High-Performance Solid-State Sodium Metal Batteries.

Rechargeable solid-state Na metal batteries (SSNMB) can offer high operational safety and energy density. However, poor solid-solid contact between the electrodes and the electrolyte can dramatically increase interfacial resistance and Na dendrite formation, even at low current rates. Therefore, we developed a carbon-fiber-supported liquid Na-K alloy anode that ensures close anode-electrolyte contact, enabling superior cycle stability and rate capability. We then demonstrated the first cryogenic transmission electron microscopy (cryo-TEM) characterization of an SSNMB, capturing the evolution of solid-electrolyte interphase (SEI) and revealing both crystalline and amorphous phases, which could facilitate ion transport and prevent continuous side reactions. By enhancing contact between the Na-K alloy and solid-state electrolyte, these symmetric cells are capable of cycling for over 800 h without notable increased polarization and enable an unprecedented critical current density (CCD) at 40 mA cm-2. Our liquid Na-K alloy approach offers a promising strategic avenue toward commercial SSNMBs.

Bismuth Ferrite as an Electrocatalyst for the Electrochemical Nitrate Reduction.

Electrochemical nitrate reduction has become an appealing "waste-to-wealth" approach for sustainable NH3 synthesis owing to its mild operating conditions. However, developing catalysts with high activities and Faradaic efficiencies for this complicated eight-electron reaction is a great challenge. Herein, bismuth ferrite (BiFeO3) flakes, with a distorted perovskite-type structure, are demonstrated to be excellent catalysts for electrochemical NH3 synthesis via nitrate reduction, with a maximum Faradaic efficiency of 96.85%, NH3 yield of 90.45 mg h-1 mgcat-1, at -0.6 V vs. reversible hydrogen electrode. During the nitrate reduction reaction, the crystalline BiFeO3 rapidly converts into an amorphous phase, which is stable in the long term reaction. These results open a new window for rational design of more active and durable electrocatalysts.

Enabling Ultrastable Alkali Metal Anodes by Artificial Solid Electrolyte Interphase Fluorination.

The high specific capacity of alkalic metal (Li, Na, and K) anodes has drawn widespread interest; however, the practical applications of alkalic metal anodes have been hampered by dendrite growth and interfacial instability, resulting in performance deterioration and even safety issues. Here, we describe a simple method for building tunable fluoride-based artificial solid-electrolyte interphase (SEI) from the fluorination reaction of alkali metals with a mild organic fluorinating reagent. Comprehensive characterization by advanced electron microscopes shows that the LiF-based artificial SEI adopts a crystal-glass structure, which enables efficient Li ion transport and improves structural integrity against the volume changes that occur during Li plating/stripping. Compared with bare Li anode, the ones with artificial SEI exhibit decreased voltage hysteresis, enhanced rate capability, and prolonged cycle life. This method is also applied to generate fluoride-based artificial SEI on Na and K metal anodes that brings significant improvement in battery performance.

Demographic inequities exist and influence transplant outcomes in liver transplantation for acute alcohol-associated hepatitis.

BACKGROUND: Liver transplantation has inherent disparities but data is scarce in liver transplant (LT) candidates with acute alcohol-associated hepatitis (AAH). We aimed to investigate demographic inequities and its impact on survival outcomes among AAH LT candidates. METHODS: A retrospective analysis using the United Network of Organ Sharing database was conducted between 2000 and 2021. 25 981 LT recipients with alcohol-associated liver cirrhosis and 662 recipients with AAH were included. Waitlisted candidates were also evaluated. RESULTS: In comparison with alcohol-associated liver cirrhosis, AAH LT recipients were more likely Asian or "other" race and younger. Hispanics demonstrated better graft and patient survival (p < 0.05) but were less likely to be waitlisted and transplanted for AAH than for liver cirrhosis. Women with AAH were more likely to be waitlisted and transplanted. Pre-existing diabetes and male sex were associated with higher graft failure (25% and 8% respectively). Increasing recipient age were 2% more likely to experience negative outcomes. Chronicity of liver disease did not impact graft (p = 0.137) or patient survival (p = 0.145). CONCLUSION: Our results revealed demographic factors have a significant impact on transplant listing, organ allocation and survival outcomes. Further investigations are imperative to minimize disparities in LT evaluation and provide equity in healthcare.

Superstructure-Induced Hierarchical Assemblies for Nanoconfined Photocatalysis.

Most attempts to synthesize supramolecular nanosystems are limited to a single mechanism, often resulting in the formation of nanomaterials that lack diversity in properties. Herein, hierarchical assemblies with appropriate variety are fabricated in bulk via a superstructure-induced organic-inorganic hybrid strategy. The dynamic balance between substructures and superstructures is managed using covalent organic frameworks (COFs) and metal-organic frameworks (MOFs) as dual building blocks to regulate the performances of hierarchical assemblies. Significantly, the superstructures resulting from the controlled cascade between COFs and MOFs create highly active photocatalytic systems through multiple topologies. Our designed tandem photocatalysis can precisely and efficiently regulate the conversion rates of bioactive molecules (benzo[d]imidazoles) through competing redox pathways. Furthermore, benzo[d]imidazoles catalyzed by such supramolecular nanosystems can be isolated in yields ranging from 70 % to 93 % within tens of minutes. The multilayered structural states within the supramolecular systems demonstrate the importance of hierarchical assemblies in facilitating photocatalytic propagation and expanding the structural repertoire of supramolecular hybrids.

Restoration of Cullin3 gene expression enhances the improved effects of sonic hedgehog signaling activation for hypertension and attenuates the dysfunction of vascular smooth muscle cells.

BACKGROUND: Hypertension is known as a major factor for global mortality. We aimed to investigate the role of Cullin3 (CUL3) in the regulation of hypertension. MATERIAL AND METHODS: Human vascular smooth muscle cells (VSMCs) were treated with Angiotensin II (Ang II) to establish a hypertension in vitro model. Cell viability was detected by a cell counting kit-8 (CCK-8) assay. The content of reactive oxygen species (ROS) was evaluated by kit. Transwell assay and TUNEL staining were, respectively, used to assess cell migration and apoptosis. Additionally, the expression of sonic hedgehog (SHH) signaling-related proteins (SHH, smoothened homolog (Smo) and glioblastoma (Gli)) and CUL3 was tested with western blotting. Following treatment with Cyclopamine (Cycl), an inhibitor of SHH signaling, in Ang II-induced VSMCs, cell viability, migration, apoptosis and ROS content were determined again. Then, VSMCs were transfected with CUL3 plasmid or/and treated with sonic hedgehog signaling agonist (SAG) to explore the impacts on Ang II-induced VSMCs damage. In vivo, a hypertensive mouse model was established. Systolic blood pressure and diastolic blood pressure were determined. The histopathologic changes of abdominal aortic tissues were examined using H&E staining. The expression of SHH, Smo, Gli and CUL3 was tested with western blotting. RESULTS: Significantly increased proliferation, migration and apoptosis of VSMCs were observed after Ang II exposure. Moreover, Ang II induced upregulated SHH, Smo and Gli expression, whereas limited increase in CUL3 expression was observed. The content of ROS in Ang II-stimulated VSMCs presented the same results. Following Cycl treatment, the high levels of proliferation and migration in Ang II-treated VSMCs were notably remedied while the apoptosis and ROS concentration were further increased. Moreover, Cycl downregulated SHH, Smo, Gli and CUL3 expression. Above-mentioned changes caused by Ang II were reversed following SAG addition. Indeed, SAG treatment combined with restoration of CUL3 expression inhibited proliferation, migration, apoptosis and ROS level in Ang II-stimulated VSMCs. In vivo, SAG aggravated the histopathological changes of the aorta and with a worse tendency after both SAG intervention and CUL3 silencing. By contrast, SAG treatment and rebound in CUL3 expression alleviated the vascular damage. CONCLUSIONS: Collectively, restoration of CUL3 gene expression protected against hypertension through enhancing the effects of SHH activation in inhibition of apoptosis and oxidative stress for hypertension and alleviating the dysfunction of VSMCs.

A Water-Soluble Leggero Pillar[5]arene.

The study of aqueous-phase molecular recognition of artificial receptors is one of the frontiers in supramolecular chemistry since most biochemical processes and reactions take place in an aqueous medium and heavily rely on it. In this work, a water-soluble version of leggero pillar[5]arene bearing eight positively charged pyridinium moieties (CWP[5]L) was designed and synthesized, which exhibited good binding affinities with certain aliphatic sulfonate species in aqueous solutions. Significantly, control experiments demonstrate that the guest binding performance of CWP[5]L is superior to its counterpart water-soluble macrocyclic receptor in traditional pillararenes.

Modulating Supramolecular Charge-Transfer Interactions in the Solid State using Compressible Macrocyclic Hosts.

Modulating intermolecular charge-transfer (ICT) interactions between specific donor and acceptor species in host-guest systems is a big challenge and full of research value in supramolecular chemistry and materials science. In this work, a strategy to modulate the supramolecular ICT interactions in the solid state is developed by compressing the binding cavity of a macrocyclic host named perethylated leaning pillar[6]arene (p-EtLP6). The solid-state ICT affinities of p-EtLP6 toward multi-types of electron-deficient planar guests could be significantly enhanced by transforming the macrocyclic backbone from the original para-bridged mode into a hybrid para- and meta-bridged isomeric form (m-EtLP6). X-ray single-crystal structural analyses incorporating theoretical calculation demonstrate that the improved ICT affinities are mainly attributed to the superior host-guest size fit arising from the compressed binding cavity in m-EtLP6 as compared with p-EtLP6.

Single Iridium Atom Doped Ni2P Catalyst for Optimal Oxygen Evolution.

Single-atom catalysts (SACs) with 100% active sites have excellent prospects for application in the oxygen evolution reaction (OER). However, further enhancement of the catalytic activity for OER is quite challenging, particularly for the development of stable SACs with overpotentials <180 mV. Here, we report an iridium single atom on Ni2P catalyst (IrSA-Ni2P) with a record low overpotential of 149 mV at a current density of 10 mA·cm-2 in 1.0 M KOH. The IrSA-Ni2P catalyst delivers a current density up to ∼28-fold higher than that of the widely used IrO2 at 1.53 V vs RHE. Both the experimental results and computational simulations indicate that Ir single atoms preferentially occupy Ni sites on the top surface. The reconstructed Ir-O-P/Ni-O-P bonding environment plays a vital role for optimal adsorption and desorption of the OER intermediate species, which leads to marked enhancement of the OER activity. Additionally, the dynamic "top-down" evolution of the specific structure of the Ni@Ir particles is responsible for the robust single-atom structure and, thus, the stability property. This IrSA-Ni2P catalyst offers novel prospects for simplifying decoration strategies and further enhancing OER performance.

Lck Inhibits Heat Shock Protein 65-Mediated Reverse Cholesterol Transport in T Cells.

Previously, we reported that heat shock protein (HSP)65 impairs the effects of high-density lipoprotein on macrophages. We also showed that immune response activation adversely affects reverse cholesterol transport (RCT). In this study, we investigated the effects of the Src family kinase lymphocyte-specific protein tyrosine kinase (Lck) and elucidated the mechanism underlying HSP65-regulated cholesterol efflux in T cells. We evaluated cell proliferation, Lck expression, and inflammatory cytokine production in Jurkat cells and CD4+ T cells. HSP65-mediated inhibition of RCT was assessed by evaluating ABCA1, ABCG1, SR-BI, PPAR-γ, and liver X receptor-α expression. A dose-dependent relationship was found between the levels of these proteins and the suppression of cholesterol efflux. Stimulation of Lck-silenced T cells with ionomycin resulted in a decrease in intracellular calcium levels. Treatment of Jurkat cells with PP2, an inhibitor of Src family kinase, inhibited calcium-induced, but not PMA-induced, ERK phosphorylation. NF-κB activation in response to PMA was minimally inhibited in cells stimulated with PP2. HSP65 failed to trigger downstream ERK or JNK phosphorylation or to activate NF-κB or protein kinase C-γ in Lck-silenced cells. Additionally, elevation of intracellular calcium was also impaired. However, HSP65 significantly enhanced cholesterol efflux and decreased cellular cholesterol content by inducing the expression of cholesterol transport proteins in Lck-silenced cells. The treatment of Jurkat cells with PP2 also inhibited cell proliferation and promoted RCT. In conclusion, Lck is a key molecule in the TCR signaling cascade that inhibits cholesterol efflux and upregulates intracellular cholesterol ester content in T cells. Our results demonstrate that the immune response plays a previously unrecognized role in RCT.