Steering Electron-Induced Surface Reaction via a Molecular Assembly Approach.

Electrons not only serve as a "reactant" in redox reactions but also play a role in "catalyzing" some chemical processes. Despite the significance and ubiquitousness of electron-induced chemistry, many related scientific issues still await further exploration, among which is the impact of molecular assembly. In this work, microscopic insights into the vital role of molecular assembly in tweaking the electron-induced surface chemistry are unfolded by combined scanning tunneling microscopy and density functional theory studies. It is shown that the selective dissociation of a C-Cl bond in 4,4″-dichloro-1,1':3',1''-terphenyl (DCTP) on Cu(111) can be efficiently triggered by an electron injection via the STM tip into the unoccupied molecular orbital. The DCTP molecules are embedded in different assembly structures, including its self-assembly and coassemblies with Br adatoms. The energy threshold for the C-Cl bond cleavage increases as more Br adatoms stay close to the molecule, indicative of the sensitive response of the electron-induced surface reactivity of the C-Cl bond to the subtle change in the molecular assembly. Such a phenomenon is rationalized by the energy shift of the involved unoccupied molecular orbital of DCTP that is embedded in different assemblies. These findings shed new light on the tuning effect of molecular assembly on electron-induced reactions and introduce an efficient approach to precisely steer surface chemistry.

Selective Cleavage of α-Olefins to Produce Acetylene and Hydrogen.

Acetylene production from mixed α-olefins emerges as a potentially green and energy-efficient approach with significant scientific value in the selective cleavage of C-C bonds. On the Pd(100) surface, it is experimentally revealed that C2 to C4 α-olefins undergo selective thermal cleavage to form surface acetylene and hydrogen. The high selectivity toward acetylene is attributed to the 4-fold hollow sites which are adept at severing the terminal double bonds in α-olefins to produce acetylene. A challenge arises, however, because acetylene tends to stay at the Pd(100) surface. By using the surface alloying methodology with alien Au, the surface Pd d-band center has been successfully shifted away from the Fermi level to release surface-generated acetylene from α-olefins as a gaseous product. Our study actually provides a technological strategy to economically produce acetylene and hydrogen from α-olefins.

Unraveling the relationship between soil carbon-degrading enzyme activity and carbon fraction under biogas slurry topdressing.

Biogas slurry, a by-product of the anaerobic digestion of biomass waste, predominantly consisting of livestock and poultry manure, is widely acclaimed as a sustainable organic fertilizer owing to its abundant reserves of essential nutrients. Its distinctive liquid composition, when tactfully integrated with a drip irrigation system, unveils immense potential, offering unparalleled convenience in application. In this study, we investigated the impact of biogas slurry topdressing as a replacement for chemical fertilizer (BSTR) on soil total organic carbon (TOC) fractions and carbon (C)-degrading enzyme activities across different soil depths (surface, sub-surface, and deep) during the tasseling (VT) and full maturity stage (R6) of maize. BSTR increased the TOC content within each soil layer during both VT and R6 periods, inducing alterations in the content and proportion of individual C component, particularly in the topsoil. Notably, the pure biogas slurry topdressing treatment (100%BS) compared with the pure chemical fertilizer topdressing treatment (CF), exhibited a 38.9% increase in the labile organic carbon of the topsoil during VT, and a 30.3% increase in the recalcitrant organic carbon during R6, facilitating microbial nutrient utilization and post-harvest C storage during the vigorous growth period of maize. Furthermore, BSTR treatment stimulated the activity of oxidative and hydrolytic C-degrading enzymes, with the 100%BS treatment showcasing the most significant enhancements, with its average geometric enzyme activity surpassing that of CF treatment by 27.9% and 27.4%, respectively. This enhancement facilitated ongoing and efficient degradation and transformation of C. Additionally, we screened for C components and C-degrading enzymes that are relatively sensitive to BSTR. The study highlight the advantages of employing pure biogas slurry topdressing, which enhances C component and C-degrading enzyme activity, thereby reducing the risk of soil degradation. This research lays a solid theoretical foundation for the rational recycling of biogas slurry.

Clustering-Evolved Frontier Orbital for Low-Temperature CO2 Dissociation.

In this study, single Ni2 clusters (two Ni atoms bridged by a lattice oxygen) are successfully synthesized on monolayered CuO. They exhibit a remarkable activity toward low-temperature CO2 thermal dissociation, in contrast to cationic Ni atoms that nondissociatively adsorb CO2 and metallic Ni ones that are chemically inert for CO2 adsorption. Density functional theory calculations reveal that the Ni2 clusters can significantly alter the spatial symmetry of their unoccupied frontier orbitals to match the occupied counterpart of the CO2 molecule and enable its low-temperature dissociation. This study may help advance single-cluster catalysis and exploit the unexcavated mechanism for low-temperature CO2 activation.

Versatile modulators for laser-based FEL seeding at SwissFEL.

The Paul Scherrer Institute is implementing laser-based seeding in the soft X-ray beamline (Athos) of its free-electron laser, SwissFEL, to enhance the temporal and spectral properties of the delivered photon pulses. This technique requires, among other components, two identical modulators for coupling the electron beam with an external laser with a wavelength range between 260 and 1600 nm. The design, magnetic measurements results, alignment, operation and also details of the novel and exotic magnetic configuration of the prototype are described.

Disentangling the impact of biogas slurry topdressing as a replacement for chemical fertilizers on soil bacterial and fungal community composition, functional characteristics, and co-occurrence networks.

The application of biogas slurry topdressing with drip irrigation systems can compensate for the limitation of traditional solid organic fertilizer, which can only be applied at the bottom. Based on this, we attempted to define the response of soil bacterial and fungal communities of maize during the tasseling and full maturity stages, by using a no-topdressing control and different ratios of biogas slurry nitrogen in place of chemical fertilizer topdressing. The application of biogas slurry resulted in the emergence of new bacterial phyla led by Synergistota. Compared with pure urea chemical topdressing, the pure biogas slurry topdressing treatment significantly enriched Firmicutes and Basidiomycota communities during the tasseling stage, in addition to affecting the separation of bacterial and fungal α-diversity indices between the tasseling and full maturity stages. Based on the prediction of community composition and function, the changes in bacterial and fungal communities caused by biogas slurry treatment stimulated the ability of microorganisms to decompose refractory organic components, which was conducive to turnover in the soil carbon cycle, and improved multi-element (such as sulfur) cycles; however it may also bring potential risks of heavy metal and pathogenic microbial contamination. Notably, the biogas slurry treatment reduced the correlation and aggregation of bacterial and fungal symbiotic networks, and had a dual effect on ecological randomness. These findings contribute to a deeper comprehension of the alterations occurring in soil microbial communities when substituting chemical fertilizers treated with biogas slurry topdressing, and promote the efficient and sustainable utilization of biogas slurry resources.

Biogas slurry topdressing as replacement of chemical fertilizers reduces leaf senescence of maize by up-regulating tolerance mechanisms.

Worldwide physiological research has aimed to decelerate the aging of crop leaves by optimizing fertilization measures to improve crop or biomass yield. Solid organic fertilizers can be combined with chemical fertilizers to delay the aging of crop leaves. Biogas slurry is a liquid organic fertilizer produced by the anaerobic fermentation of livestock and poultry manure and other resources, and it can partially replace chemical fertilizers in field application via drip irrigation systems. However, the impact of biogas slurry topdressing on leaf aging remains unclear. This study investigated treatments with no topdressing (control, CK) and five topdressing patterns of biogas slurry replacing chemical fertilizer (nitrogen) at 100%, 75%, 50%, 25%, and 0% (100%BS, 75%BS, 50%BS, 25%BS, CF). The effects of different proportions of biogas slurry on leaf senescence rate, photosynthetic pigments, osmotic adjustment substances, antioxidant defense enzymes, and nitrogen metabolism related enzyme activities of maize were analyzed. Subsequently, the mechanisms of biogas slurry topdressing on the leaf senescence rate of maize were explored. The results showed that the mean decreasing rate of relative green leaf area (Vm) treated with biogas slurry decreased by 3.7%-17.1% and the duration of leaf area duration (LAD) increased by 3.7%-17.1% compared with the results for CK. The maximum senescence rate of 100%BS was delayed by 4.4 and 5.6 d compared to the results for CF and CK, respectively. During the senescence of maize leaves, the use of biogas slurry topdressing increased the content of chlorophyll, decreased the water loss and the accumulation rate of malondialdehyde and proline in leaves, and increased the activities of catalase, peroxidase, and superoxide dismutase in the later growth and development periods of maize. In addition, biogas slurry topdressing improved the nitrogen transport efficiency of the leaves and ensured continuous and efficient ammonium assimilation. Furthermore, there was a strong correlation between leaf senescence and the investigated physiological indices. Cluster analysis showed that the 100%BS treatment exhibited the most prominent effect on leaf senescence. Biogas slurry topdressing as a substitute for chemical fertilizer can be potentially used as an anti-aging regulation measure for crops to decrease the damage induced by senescence.

Synergistic Lysosomal Impairment and ER Stress Activation for Boosted Autophagy Dysfunction Based on Te Double-Headed Nano-Bullets.

To overcome the autophagy compromised mechanism of protective cellular processes by "eating"/"digesting" damaged organelles or potentially toxic materials with autolysosomes in tumor cells, lysosomal impairment can be utilized as a traditional autophagy dysfunction route for tumor therapy; however, this conventional one-way autophagy dysfunction approach is always limited by the therapeutic efficacy. Herein, an innovative pharmacological strategy that can excessively provoke autophagy via endoplasmic reticulum (ER) stress is implemented along with lysosomal impairment to enhance autophagy dysfunction. In this work, the prepared tellurium double-headed nanobullets (TeDNBs) with controllable morphology are modified with human serum albumin (HSA) which facilitates internalization by tumor cells. On the one hand, ER stress can be stimulated by upregulating the phosphorylation eukaryotic translation initiation factor 2 (P-eIF2α) owing to the production of tellurite (TeO32- ) in the specifical hydrogen peroxide-rich tumor environment; thus, autophagy overstimulation occurs. On the other hand, OME can deacidify and impair lysosomes by downregulating lysosomal-associated membrane protein 1 (LAMP1), therefore blocking autolysosome formation. Both in vitro and in vivo results demonstrate that the synthesized TeDNBs-HSA/OME (TeDNBs-HO) exhibit excellent therapeutic efficacy by autophagy dysfunction through ER stress induction and lysosomal damnification. Thus, TeDNBs-HO is verified to be a promising theranostic nanoagent for effective tumor therapy.

A Deafness- and Diabetes-associated tRNA Mutation Causes Deficient Pseudouridinylation at Position 55 in tRNAGlu and Mitochondrial Dysfunction.

Several mitochondrial tRNA mutations have been associated with maternally inherited diabetes and deafness. However, the pathophysiology of these tRNA mutations remains poorly understood. In this report, we identified the novel homoplasmic 14692A→G mutation in the mitochondrial tRNAGlu gene among three Han Chinese families with maternally inherited diabetes and deafness. The m.14692A→G mutation affected a highly conserved uridine at position 55 of the TΨC loop of tRNAGlu The uridine is modified to pseudouridine (Ψ55), which plays an important role in the structure and function of this tRNA. Using lymphoblastoid cell lines derived from a Chinese family, we demonstrated that the m.14692A→G mutation caused loss of Ψ55 modification and increased angiogenin-mediated endonucleolytic cleavage in mutant tRNAGlu The destabilization of base-pairing (18A-Ψ55) caused by the m.14692A→G mutation perturbed the conformation and stability of tRNAGlu An approximately 65% decrease in the steady-state level of tRNAGlu was observed in mutant cells compared with control cells. A failure in tRNAGlu metabolism impaired mitochondrial translation, especially for polypeptides with a high proportion of glutamic acid codons such as ND1, ND6, and CO2 in mutant cells. An impairment of mitochondrial translation caused defective respiratory capacity, especially reducing the activities of complexes I and IV. Furthermore, marked decreases in the levels of mitochondrial ATP and membrane potential were observed in mutant cells. These mitochondrial dysfunctions caused an increasing production of reactive oxygen species in the mutant cells. Our findings may provide new insights into the pathophysiology of maternally inherited diabetes and deafness, which is primarily manifested by the deficient nucleotide modification of mitochondrial tRNAGlu.

Controllable Synthesis and Properties of Sb2Se3 Nanorods Synthesized by Hot-Injection Method.

Antimony selenide (Sb2Se3) is an interesting p-type semiconductor with a proper bandgap for photovoltaic devices. In this work, Sb2Se3 nanorods with controllable length-width ratios were synthesized via hot-injection method, where selenium powder was used as selenium sources and oleylamine was selected as reducing agent and high-point solvent. X-ray diffraction (XRD) patterns and high resolution Transmission electron microscope (HRTEM) results demonstrate that nanorods are wellcrystallized single crystalline and grow along the [110] direction. The reaction temperatures were found to have a noticeable influence on the morphologies of Sb2Se3 nanorods. The growth mechanism of the nanorods was discussed based on scanning electron microscope (SEM) observations. Vis-NIR absorption spectra reveal that the bandgaps of nanorods were between 0.75 eV and 1.1 eV. Electrical conductivities in dark and light were also investigated.

[Progress in research on pathogenic genes and gene therapy for inherited retinal diseases].

Inherited retinal diseases (IRDs), including retinitis pigmentosa, Usher syndrome, Cone-Rod degenerations, inherited macular dystrophy, Leber's congenital amaurosis, Leber's hereditary optic neuropathy are the most common and severe types of hereditary ocular diseases. So far more than 200 pathogenic genes have been identified. With the growing knowledge of the genetics and mechanisms of IRDs, a number of gene therapeutic strategies have been developed in the laboratory or even entered clinical trials. Here the progress of IRD research on the pathogenic genes and therapeutic strategies, particularly gene therapy, are reviewed.

Characteristics and partitions of traditional and emerging organophosphate esters in soil and groundwater based on machine learning.

Organophosphate esters (OPEs) pose hazards to both humans and the environment. This study applied target screening to analyze the concentrations and detection frequencies of OPEs in the soil and groundwater of representative contaminated sites in the Pearl River Delta. The clusters and correlation characteristics of OPEs in soil and groundwater were calculated by self-organizing map (SOM). The risk assessment and partitions of OPEs in industrial park soil and groundwater were conducted. The results revealed that 14 out of 23 types of OPEs were detected. The total concentrations (Σ23OPEs) ranged from 1.931 to 743.571 ng/L in the groundwater, and 0.218 to 79.578 ng/g in the soil, the former showed highly soluble OPEs with high detection frequencies and concentrations, whereas the latter exhibited the opposite trend. SOM analysis revealed that the distribution of OPEs in the soil differed significantly from that in the groundwater. In the industrial park, OPEs posed acceptable risks in both the soil and groundwater. The soil could be categorized into Zone I and II, and the groundwater into Zone I, II, and III, with corresponding management recommendations. Applying SOM to analyze the characteristics and partitions of OPEs may provide references for other new pollutants and contaminated sites.

Comparison of amino acid metabolism in frozen-thawed and fresh early-stage human embryos.

AIMS: To compare the amino acid differences of changes of frozen-thawed early-stage human embryos and fresh cultured early-stage human embryos. MATERIAL AND METHODS: Discarded embryos and their in vitro culture medium of patients who underwent in vitro fertilization-embryo transfer (IVF-ET) at the Research Center for Reproductive Medicine, the Sixth Affiliated Hospital of Sun Yat-sen University, from September 2010 to April 2011 were collected. Amino acid levels were determined by high performance liquid chromatography. RESULTS: The amino acid differences of changes in the culture medium of fresh embryos (661.50 µmol/L) were significantly higher than in the medium of post-thawed embryos (232.00 µmol/L) at 0.5 h (P < 0.001). At 1 and 2 h, no significant difference of change was found in all amino acids. Differences in the concentration of amino acids between post-thawed embryos and blank control medium were already present beginning at 1 h. CONCLUSIONS: The level of amino acid metabolism of frozen-thawed early-stage human embryos has already recovered from the state of metabolic stagnation during cryopreservation at 1 h of incubation after thawing, and the amino acid metabolism level at that time approximates that in fresh embryos before freezing. This may be established as the optimal embryo transfer time in IVF-ET.

Synergistic effect on soil health from combined application of biogas slurry and biochar.

Biogas slurry and biochar, as typical by-products and derivatives of organic waste, have been applied in agricultural production to improve the soil carbon (C) pool. However, whether the combined application of biogas slurry and biochar produces synergistic effects on the soil C pool and soil health requires quantitative clarification. In this study, we performed a pot experiment to analyze the changes of soil organic carbon (SOC), potassium permanganate-oxidized carbon (POXC), mineralizable carbon (MC), soil ß-glucosidase (S-ß-GC), and soil protein (SP) in different treatments at the flowering and fruit-setting stages, and full fruit stage of tomato by establishing two base fertilizer modes (base fertilizer N and base biogas slurry N), three topdressing modes (topdressing chemical fertilizer N, topdressing 50% biogas slurry N + 50% chemical fertilizer N, and topdressing biogas slurry N), and two biochar levels (no addition and 3% biochar addition). During the full fruit period, the SOC content of bottom applications of biogas slurry and topdressings of biogas slurry significantly increased by 9.92-15.52% and 13.02-18.26%, respectively (P < 0.05), when compared to chemical fertilizer bottom applications and topdressings of chemical fertilizer. When compared to non-biochar treatment, the SOC content of the biochar considerably increased by 52.56-58.94% (P < 0.05). Moreover, biogas slurry treatment increased the MC, steady-state C, and C pool index, and decreased the S-ß-GC, C pool efficiency, C pool activity, and C pool activity index. Application of biogas slurry initially reduced POXC, SP, the C pool management index, and the soil quality index; nonetheless, these indicators eventually recovered or even exceeded the result of single application chemical fertilizer. Overall, the combined application of biogas slurry and biochar strongly increases the soil C pool, improves soil health, and reduces the short-term negative effects of using only biogas slurry.

Iron-based and BRD4-downregulated strategy for amplified ferroptosis based on pH-sensitive/NIR-II-boosted nano-matchbox.

Ferroptosis (FPT), a novel form of programmed cell death, is characterized by overwhelming iron/reactive oxygen species (ROS)-dependent accumulation of lipid peroxidation (LPO). However, the insufficiency of endogenous iron and ROS level limited the FPT therapeutic efficacy to a large extent. To overcome this obstacle, the bromodomain-containing protein 4 (BRD4)-inhibitor (+)-JQ1 (JQ1) and iron-supplement ferric ammonium citrate (FAC)-loaded gold nanorods (GNRs) are encapsulated into the zeolitic imidazolate framework-8 (ZIF-8) to form matchbox-like GNRs@JF/ZIF-8 for the amplified FPT therapy. The existence of matchbox (ZIF-8) is stable in physiologically neutral conditions but degradable in acidic environment, which could prevent the loaded agents from prematurely reacting. Moreover, GNRs as the drug-carriers induce the photothermal therapy (PTT) effect under the irradiation of near-infrared II (NIR-II) light owing to the absorption by localized surface plasmon resonance (LSPR), while the hyperthermia also boosts the JQ1 and FAC releasing in the tumor microenvironment (TME). On one hand, the FAC-induced Fenton/Fenton-like reactions in TME can simultaneously generate iron (Fe3+/Fe2+) and ROS to initiate the FPT treatment by LPO elevation. On the other hand, JQ1 as a small molecule inhibitor of BRD4 protein can amplify FPT through downregulating the expression of glutathione peroxidase 4 (GPX4), thus inhibiting the ROS elimination and leading to the LPO accumulation. Both in vitro and in vivo studies reveal that this pH-sensitive nano-matchbox achieves obvious suppression of tumor growth with good biosafety and biocompatibility. As a result, our study points out a PTT combined iron-based/BRD4-downregulated strategy for amplified ferrotherapy which also opens the door of future exploitation of ferrotherapy systems.

Remodeling of the liver fibrosis microenvironment based on nilotinib-loaded multicatalytic nanozymes with boosted antifibrogenic activity.

Liver fibrosis is a reversible pathological process caused by chronic liver damage and a major risk factor for hepatocellular carcinoma (HCC). Hepatic stellate cell (HSC) activation is considered the main target for liver fibrosis therapy. However, the efficiency of this strategy is limited due to the complex microenvironment of liver fibrosis, including excessive extracellular matrix (ECM) deposition and hypoxia-induced imbalanced ECM metabolism. Herein, nilotinib (NIL)-loaded hyaluronic acid (HA)-coated Ag@Pt nanotriangular nanozymes (APNH NTs) were developed to inhibit HSCs activation and remodel the microenvironment of liver fibrosis. APNH NTs efficiently eliminated intrahepatic reactive oxygen species (ROS) due to their inherent superoxide dismutase (SOD) and catalase (CAT) activities, thereby downregulating the expression of NADPH oxidase-4 (NOX-4) and inhibiting HSCs activation. Simultaneously, the oxygen produced by the APNH NTs further alleviated the hypoxic microenvironment. Importantly, the released NIL promoted collagen depletion by suppressing the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), thus synergistically remodeling the microenvironment of liver fibrosis. Notably, an in vivo study in CCl4-induced mice revealed that APNH NTs exhibited significant antifibrogenic effects without obvious long-term toxicity. Taken together, the data from this work suggest that treatment with the synthesized APNH NTs provides an enlightening strategy for remodeling the microenvironment of liver fibrosis with boosted antifibrogenic activity.

Supramolecular Hydrogel Based on Pseudopolyrotaxane Aggregation for Bacterial Microenvironment-Responsive Antibiotic Delivery.

Due to the extensive use of antibiotics, the variety and number of drug-resistant pathogens have increased dramatically and have become a major global health problem. This imposes significant demands on the rational and effective use of antibiotics. To this end, a supramolecular hydrogel based on pseudopolyrotaxanes aggregation is proposed for antibiotic delivery. Supramolecular cross-linking strategies allow hydrogels to be obtained under mild conditions that facilitate the encapsulation of antibiotics. The presence of pH-sensitive imine bonds allows for the reversible detachment of PEG residues from the PEGylated hyaluronic acid backbone in an acidic environment, which leads to reversible changes in hydrogel crosslink density and thus controls antibiotic release behavior. Antimicrobial assessments indicated that the hydrogel exhibited good antimicrobial efficiency against both Gram-positive and negative bacteria, while responding to the bacterial microenvironment and enabling a burst release of antibiotics in severe infections. The proposed hydrogel also has excellent biocompatibility and thus possesses great potential for biomedical applications.

Sequential delivery for hepatic fibrosis treatment based on carvedilol loaded star-like nanozyme.

Hepatic fibrosis, characterized by excessive reactive oxygen species (ROS) generation, hepatic stellate cells (HSCs) activation, and enormous extracellular matrix (ECM) production, can further cause liver cirrhosis, liver failure and liver cancer. However, the combination of limited solubility, low targeting, uncontrolled release and the sophisticated physiological barriers are tremendous challenges for therapeutic effect. In this study, we engineered a sequential delivery strategy based on autophagy inhibitor carvedilol (CAR) loaded and hyaluronic acid (HA) modified star-like Au nanozyme (Au NS@CAR-HA) for targeted HSCs suppression. In hepatic fibrosis acidic environment, CAR-HA can be firstly detached from Au NS@CAR-HA. Then, CAR would be released from CAR-HA conjugation by chemical bond breakage which triggered by intracellular acid potential, thus could suppressing autolysosome generation by up-regulation of autosome and lysosome pH value to inhibit HSCs activation. Meanwhile, Au NS exhibited enhanced ROS scavenging efficiency of hydrogen peroxides and superoxide, which was helpful to restrain the activity of peroxisome proliferators-activated receptors ß (PPARß) and c-Jun N-terminal kinase (JNK), thereby reducing HSCs proliferation to enhance HSCs inactivation efficacy. In conclusion, Au NS@CAR-HA can attenuate hepatic fibrosis via regulating the proliferation and activation of hepatic stellate cells, which provides a new strategy for hepatic fibrosis treatment.

Turning Hot into Cold: Immune Microenvironment Reshaping for Atherosclerosis Attenuation Based on pH-Responsive shSiglec-1 Delivery System.

Current atherosclerosis treatment is based on a combination of cholesterol-lowering medication and low-fat diets; however, the clinical effect is unsatisfactory. It has been shown that the level of immune cell infiltration and pro-inflammatory factors in the atherosclerotic immune microenvironment (AIM) play important roles in the development and progression of atherosclerosis. Therefore, we hypothesized that reshaping "hot AIM" into "cold AIM" could attenuate atherosclerosis. For this purpose, we designed a pH-responsive and charge-reversible nanosystem, referred to as Au-PEI/shSiglec-1/PEI-acetylsalicylic acid (ASPA NPs) to effectively deliver shSiglec-1, which blocked the interactions between macrophages with CD8+ T/NKT cells, thus inhibiting immune cell infiltration. Further, we demonstrated that acetylsalicylic acid (ASA), detached from the pH-responsive PEI-ASA polymer, and inhibited lipid accumulation in macrophage, thereby decreasing the lipid antigen presentation. Additionally, reduced macrophage-produced inflammatory factors by ASA and low CD8+ T/NKT cell infiltration levels synergistically inhibit Th17 cell differentiation, thus further dramatically attenuating inflammation in AIM by decreasing the IL-17A production. Eventually, ASPA NPs efficiently reshaped AIM by inhibiting immune cell infiltration, lipid antigen presentation, and pro-inflammation, which provided a feasible therapeutic strategy for atherosclerosis immunotherapy.

Triangular-shaped homologous heterostructure as photocatalytic H2S scavenger and macrophage modulator for rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) is a chronic arthropathy causing cartilage destruction, bone erosion, and even disability. Although some advances in RA treatment have been made based on inflammatory cytokine inhibition, long-term treatment and drug effect have been restrained by severe side effects. Herein, we developed a resveratrol (RSV)-loaded Ag/Ag2S triangular-shaped homologous heterostructure with polyethylene glycol/folic acid (PEG/FA) modification (Ag/Ag2S-PEG-FA/RSV NTs) to simultaneously suppress inflammatory cytokine over-expression through photocatalytic H2S scavenging and macrophage polarization stimulation. On one hand, the over-expressed H2S, which acted as a pro-inflammatory mediator to activate the MAPK/ICAM-1 pathway and exacerbate inflammation, was eliminated through photocatalysis. The homologous Ag and Ag2S of the heterostructure enhanced electron separation and transfer by acting as a charge acceptor and electron generator, respectively, which restrained electron/hole recombination and promoted photocatalysis efficiency. Additionally, the intrinsic superoxide dismutase (SOD) and catalase (CAT) activity of Ag decomposed the reactive oxygen species (ROS) over-expressed in the RA microenvironment, which supplied O2 for the photocatalytic H2S scavenging progress. On the other hand, RSV, a natural product with anti-inflammatory activity, could be delivered to the inflammatory joint by the targeting effect of PEG-FA, thus inhibiting the IκB/NF-κB pro-inflammatory pathway to induce macrophage interconversion balance from M1 to M2. As expected, the Ag/Ag2S-PEG-FA/RSV NTs exhibited H2S scavenging capacity and modulated macrophage polarization to reduce the inflammatory cytokine level and halt RA progression in vitro and in vivo. Overall, this study revealed a therapeutic strategy with high efficacy, which opens broad prospects for RA treatment.