Co-production of 1,3-propanediol and phage phiKpS2 from the glycerol fermentation by Klebsiella pneumoniae.

As an alternative to antibiotics in response to antimicrobial-resistant infections, bacteriophages (phages) are garnering renewed interest in recent years. However, the massive preparation of phage is restricted using traditional pathogens as host cells, which incurs additional costs and contamination. In this study, an opportunistic pathogen, Klebsiella pneumoniae used to convert glycerol to 1,3-propanediol (1,3-PDO), was reused to prepare phage after fermentation. The phage infection showed that the fed-batch fermentation broth containing 71.6 g/L 1,3-PDO can be directly used for preparation of phage with a titer of 1 × 108 pfu/mL. Then, the two-step salting-out extraction was adopted to remove most impurities, e.g. acetic acid (93.5%), ethanol (91.5%) and cells (99.4%) at the first step, and obtain 1,3-PDO (56.6%) in the top phase as well as phage (97.4%) in the middle phase at the second step. This integrated process provides a cheap and environment-friendly manner for coproduction of 1,3-PDO and phage.

Noncoding RNA Terc-53 and hyaluronan receptor Hmmr regulate ageing in mice.

One of the basic questions in the ageing field is whether there is fundamental difference between the ageing of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-ageing Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at early age was observed, indicating its involvement in normal ageing of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal ageing. AAV-delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan (Stern 2017). These findings demonstrate the complexity of ageing in mammals, and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.

Adipocyte-targeted delivery of rosiglitazone with localized photothermal therapy for the treatment of diet-induced obesity in mice.

Obesity represents a growing public health concern and is closely associated with metabolic complications such as diabetes and fatty liver disease. Anti-obesity medications currently available have limited efficacy in weight loss and are often accompanied by adverse effects. This study proposes a localized photothermal therapy (PTT) combined with adipocyte-targeted delivery of rosiglitazone (RSG) to address obesity. Specifically, cationic albumin nanoparticles (cNPs) were synthesized to deliver RSG precisely to white adipocytes, stimulating the browning process. An IR780-loaded thermosensitive hydrogel was injected and allowed to gel in situ to afford a subcutaneous reservoir that enables localized PTT and controlled release of RSG cNPs. Notably, cNPs significantly enhanced the internalization efficiency in adipocytes in vitro and prolonged the therapeutic retention in the adipose tissue in vivo. Co-administration of RSG cNPs and PTT substantially reduced fat content, induced browning in white adipose tissue in diet-induced obese mice, and mitigated complications such as insulin resistance, fatty liver, and hyperlipidemia. The increased expression of uncoupling protein 1 contributes to enhancing energy expenditure and facilitating adipose metabolism, thereby effectively combating obesity. This therapeutic approach integrates localized PTT with adipocyte-targeted delivery to combat the global obesity epidemic thus offering a promising solution with reduced systemic toxicity and enhanced efficacy. STATEMENT OF SIGNIFICANCE: Cationic albumin nanoparticles are capable of efficient internalization in adipocytes, which may enhance drug targeting to adipose tissue. The combination of rosiglitazone-loaded cationic albumin nanoparticles and local hyperthermia effectively reduces lipid accumulation in adipocytes and induces an upregulated expression of uncoupling protein 1. The combination therapy effectively inhibits fat accumulation, induces adipocyte browning, and regulates systemic metabolism in diet-induced obese mice.

Nitrogen-doped carbon-coated Cu0 activates molecular oxygen for norfloxacin degradation over a wide pH range.

The Fenton-like activated molecular oxygen technology demonstrates significant potential in the treatment of refractory organic pollutants in wastewater, offering promising development prospects. We prepared a N-doped C-coated copper-based catalyst Cu0/NC3-600 through the pyrolysis of Mel-modified Cu-based metal-organic framework (MOF). The results indicate that the degradation of 20 mg/L norfloxacin (NOR) was achieved using 1.0 g/L Cu0/NC3-600 across a wide pH range, with a removal rate exceeding 95 % and total organic carbon (TOC) removals approaching 70 % after 60 min at pH 5-11. The nitrogen doping enhances the electronic structure of the carbon material, facilitating the adsorption of molecular oxygen. Additionally, the formed carbon layer effectively prevent copper leaching,contributing to increased stability to a certain extent. Subsequently, we propose the catalytic reaction mechanism for the Cu0/NC/air system. Under acidic conditions, Cu0/NC3-600 activates molecular oxygen to produce the •O2-, which serves as the primary active species for NOR degradation. While in alkaline conditions, the high-valent copper species Cu3+ is generated in conjunction with •O2-, both working simultaneously for NOR degradation. Furthermore, based on the LC-MS results, we deduced four possible degradation pathways. This work offers a novel perspective on expanding the pH range of copper-based catalysts with excellent ability to activate molecular oxygen for environmental water treatment.

PCK1 attenuates tumor stemness via activating the Hippo signaling pathway in hepatocellular carcinoma.

Liver cancer stem cells were found to rely on glycolysis as the preferred metabolic program. Phosphoenolpyruvate carboxylase 1 (PCK1), a gluconeogenic metabolic enzyme, is down-regulated in hepatocellular carcinoma and is closely related to poor prognosis. The oncogenesis and progression of tumors are closely related to cancer stem cells. It is not completely clear whether the PCK1 deficiency increases the stemness of hepatoma cells and promotes the oncogenesis of hepatocellular carcinoma. Herein, the results showed that PCK1 inhibited the self-renewal property of hepatoma cells, reduced the mRNA level of cancer stem cell markers, and inhibited tumorigenesis. Moreover, PCK1 increased the sensitivity of hepatocellular carcinoma cells to sorafenib. Furthermore, we found that PCK1 activated the Hippo pathway by enhancing the phosphorylation of YAP and inhibiting its nuclear translocation. Verteporfin reduced the stemness of hepatoma cells and promoted the pro-apoptotic effect of sorafenib. Thus, combined treatment with verteporfin and sorafenib may be a potential anti-tumor strategy in hepatocellular carcinoma.

Neighbouring Synergy in High-Density Single Ir Atoms on CoGaOOH for Efficient Alkaline Electrocatalytic Oxygen Evolution.

The catalytic performance of single-atom catalysts was strictly limited by isolated single-atom sites. Fabricating high-density single atoms to realize the synergetic interaction in neighbouring single atoms could optimize the adsorption behaviors of reaction intermediates, which exhibited great potential to break performance limitations and deepen mechanistic understanding of electrocatalysis. However, the catalytic behavior governed by neighbouring single atoms is particularly elusive and has yet to be understood. Herein, we revealed that the synergetic interaction in neighbouring single atoms contributes to superior performance for oxygen evolution relative to isolated Ir single atoms. Neighbouring single atoms was achieved by fabricating high-density single atoms to narrow the distance between single atoms. Electrochemical measurements demonstrated that the Nei-Ir1/CoGaOOH with neighbouring Ir single atoms exhibited a low overpotential of 170 mV at a current density of 10 mA cm-2, and long-durable stability over 2000 h for oxygen evolution. Mechanistic studies revealed that neighbouring single atoms synergetic stabilized the *OOH intermediates via extra hydrogen bonding interactions, thus significantly reducing the reaction energy barriers, as compared to isolated Ir single atoms. The discovery of the synergetic interaction in neighbouring single atoms could offer guidance for the development of efficient electrocatalysts, thus accelerating the world's transition to sustainable energy.

Surgical outcomes for non-small cell lung cancer in younger adults: A population-based study.

BACKGROUND: The surgical outcomes for younger patients with non-small cell lung cancer (NSCLC) remain uncertain. The aim of this study was to investigate the clinical features long-term survival outcomes in younger individuals with NSCLC following surgery. METHODS: We queried the Surveillance, Epidemiology, and End Results database from 2010 to 2017, selecting all pathologically confirmed NSCLC cases that underwent cancer-directed surgery. Younger patients were defined as those aged 18-50 years, while older patients were 51-80 years. Propensity score matching (PSM) was implemented to mitigate selection bias. Overall survival (OS) and lung cancer-specific survival (LCSS) were compared using the Kaplan-Meier method. RESULTS: Among the 33 586 treated surgically patients, 2223 (6.6%) were young. Compared to the older group, younger patients had a higher frequency of female gender, non-white ethnicity, carcinoid tumors, stage IV disease, pneumonectomy, and postoperative adjuvant therapies. The 5-year OS rates were significantly higher for younger patients (79.3% vs. 62.0%; p < 0.001), as were the 5-year LCSS rates (82.4% vs. 71.8%; p < 0.001). Post-PSM, younger patients consistently demonstrated significantly better OS and LCSS. Further stage-specific analysis revealed significantly improved 5-year OS rates at each stage and superior 5-year LCSS for stages I-II among younger patients. However, there was no statistically significant difference in LCSS for stages III-IV. CONCLUSIONS: Overall, younger patients with NSCLC treated surgically exhibit superior OS and LCSS compared to their older counterparts, although no statistically significant difference in LCSS for stages III-IV was observed between the two age groups.

UBAP2L ensures homeostasis of nuclear pore complexes at the intact nuclear envelope.

Assembly of macromolecular complexes at correct cellular sites is crucial for cell function. Nuclear pore complexes (NPCs) are large cylindrical assemblies with eightfold rotational symmetry, built through hierarchical binding of nucleoporins (Nups) forming distinct subcomplexes. Here, we uncover a role of ubiquitin-associated protein 2-like (UBAP2L) in the assembly and stability of properly organized and functional NPCs at the intact nuclear envelope (NE) in human cells. UBAP2L localizes to the nuclear pores and facilitates the formation of the Y-complex, an essential scaffold component of the NPC, and its localization to the NE. UBAP2L promotes the interaction of the Y-complex with POM121 and Nup153, the critical upstream factors in a well-defined sequential order of Nups assembly onto NE during interphase. Timely localization of the cytoplasmic Nup transport factor fragile X-related protein 1 (FXR1) to the NE and its interaction with the Y-complex are likewise dependent on UBAP2L. Thus, this NPC biogenesis mechanism integrates the cytoplasmic and the nuclear NPC assembly signals and ensures efficient nuclear transport, adaptation to nutrient stress, and cellular proliferative capacity, highlighting the importance of NPC homeostasis at the intact NE.

Biodegradation of various grades of polyethylene microplastics by Tenebrio molitor and Tenebrio obscurus larvae: Effects on their physiology.

Polyethylene (PE) is the most productive plastic product and includes three major polymers including high-density polyethylene (HDPE), linear low-density polyethylene (LLDPE) and low-density polyethylene (LDPE) variation in the PE depends on the branching of the polymer chain and its crystallinity. Tenebrio obscurus and Tenebrio molitor larvae biodegrade PE. We subsequently tested larval physiology, gut microbiome, oxidative stress, and PE degradation capability and degradation products under high-purity HDPE, LLDPE, and LDPE powders (<300 µm) diets for 21 days at 65 ± 5% humidity and 25 ± 0.5 °C. Our results demonstrated the specific PE consumption rates by T. molitor was 8.04-8.73 mg PE ∙ 100 larvae-1⋅day-1 and by T. obscurus was 7.68-9.31 for LDPE, LLDPE and HDPE, respectively. The larvae digested nearly 40% of the ingested three PE and showed similar survival rates and weight changes but their fat content decreased by 30-50% over 21-day period. All the PE-fed groups exhibited adverse effects, such as increased benzoquinone concentrations, intestinal tissue damage and elevated oxidative stress indicators, compared with bran-fed control. In the current study, the digestive tract or gut microbiome exhibited a high level of adaptability to PE exposure, altering the width of the gut microbial ecological niche and community diversity, revealing notable correlations between Tenebrio species and the physical and chemical properties (PCPs) of PE-MPs, with the gut microbiome and molecular weight change due to biodegradation. An ecotoxicological simulation by T.E.S.T. confirmed that PE degradation products were little ecotoxic to Daphnia magna and Rattus norvegicus providing important novel insights for future investigations into the environmentally-friendly approach of insect-mediated biodegradation of persistent plastics.

Anti-osteosarcoma trimodal synergistic therapy using NiFe-LDH and MXene nanocomposite for enhanced biocompatibility and efficacy.

Osteosarcoma is usually resistant to immunotherapy and, thus primarily relies on surgical resection and high-dosage chemotherapy. Unfortunately, less invasive or toxic therapies such as photothermal therapy (PTT) and chemodynamic therapy (CDT) generally failed to show satisfactory outcomes. Adequate multimodal therapies with proper safety profiles may provide better solutions for osteosarcoma. Herein, a simple nanocomposite that synergistically combines CDT, PTT, and chemotherapy for osteosarcoma treatment was fabricated. In this composite, small 2D NiFe-LDH flakes were processed into 3D hollow nanospheres via template methods to encapsulate 5-Fluorouracil (5-FU) with high loading capacity. The nanospheres were then adsorbed onto larger 2D Ti3C2 MXene monolayers and finally shielded by bovine serum albumin (BSA) to form 5-FU@NiFe-LDH/Ti3C2/BSA nanoplatforms (5NiTiB). Both in vitro and in vivo data demonstrated that the 5-FU induced chemotherapy, NiFe-LDH driven chemodynamic effects, and MXene-based photothermal killing collectively exhibited a synergistic "all-in-one" anti-tumor effect. 5NiTiB improved tumor suppression rate from <5% by 5-FU alone to ∼80.1%. This nanotherapeutic platform achieved higher therapeutic efficacy with a lower agent dose, thereby minimizing side effects. Moreover, the composite is simple to produce, enabling the fine-tuning of dosages to suit different requirements. Thus, the platform is versatile and efficient, with potential for further development.

Inhibition of ion diffusion/migration in perovskite p-n homojunction by polyetheramine insert layer to enhance stability of perovskite solar cells with p-n homojunction structure.

Perovskite p-n homojunctions (PHJ) have been confirmed to play a crucial role in facilitating carrier separation/extraction in the perovskite absorption layer and provide an additional built-in potential, which benefits the inhibition of carrier recombination in perovskite solar cells (PSCs) and ultimately improves device performance. However, the diffusion and migration of ions between n-type and p-type perovskite films, particularly under operational and heating conditions, lead to the degradation of PHJ structures and limit the long-term stability of PSCs with PHJ structure (denoted as PHJ-PSCs). In this study, we propose an insert layer strategy by directly introducing an ultra-thin polyetheramine (PEA) layer between the n-type and p-type perovskite films to address those challenges arising from ion movements. Femtosecond transient absorption (fs-TAS) and photoluminescence (PL) measurements demonstrate that the PHJ (without and with the insert layer) enhances carrier separation/extraction compared to the single n-type perovskite film. Monitoring the evolution of bromine element distribution reveals that the insert layer can efficiently suppress ion diffusion between perovskite films, even under long-term illumination and heating conditions. Consequently, an efficiency of 23.53% with excellent long-term operational stability is achieved in the optimized PHJ-PSC with the insert layer.

Zein-Based Triple-Drug Nanoparticles to Promote Anti-Inflammatory Responses for Nerve Regeneration after Spinal Cord Injury.

Defects in autophagy contribute to neurological deficits and motor dysfunction after spinal cord injury. Here a nanosystem is developed to deliver autophagy-promoting, anti-inflammatory drugs to nerve cells in the injured spinal cord. Celastrol, metformin, and everolimus as the mTOR inhibitor are combined into the zein-based nanoparticles, aiming to solubilize the drugs and prolong their circulation. The nanoparticles are internalized by BV2 microglia and SH-SY5Y neuron-like cells in culture; they inhibit the secretion of inflammatory factors by BV2 cells after insult with lipopolysaccharide, and they protect SH-SY5Y cells from the toxicity of H2O2. In a rat model of spinal cord injury, the nanoparticles mitigate inflammation and promote spinal cord repair. In the in vitro and in vivo experiments, the complete nanoparticles function better than the free drugs or nanoparticles containing only one or two drugs. These results suggest that the triple-drug nanoparticles show promise for treating spinal cord injury.

Injectable Hydrogel To Deliver Bone Mesenchymal Stem Cells Preloaded with Azithromycin To Promote Spinal Cord Repair.

Spinal cord injury is a disease that causes severe damage to the central nervous system. Currently, there is no cure for spinal cord injury. Azithromycin is commonly used as an antibiotic, but it can also exert anti-inflammatory effects by down-regulating M1-type macrophage genes and up-regulating M2-type macrophage genes, which may make it effective for treating spinal cord injury. Bone mesenchymal stem cells possess tissue regenerative capabilities that may help promote the repair of the injured spinal cord. In this study, our objective was to explore the potential of promoting repair in the injured spinal cord by delivering bone mesenchymal stem cells that had internalized nanoparticles preloaded with azithromycin. To achieve this objective, we formulated azithromycin into nanoparticles along with a trans-activating transcriptional activator, which should enhance nanoparticle uptake by bone mesenchymal stem cells. These stem cells were then incorporated into an injectable hydrogel. The therapeutic effects of this formulation were analyzed in vitro using a mouse microglial cell line and a human neuroblastoma cell line, as well as in vivo using a rat model of spinal cord injury. The results showed that the formulation exhibited anti-inflammatory and neuroprotective effects in vitro as well as therapeutic effects in vivo. These results highlight the potential of a hydrogel containing bone mesenchymal stem cells preloaded with azithromycin and trans-activating transcriptional activator to mitigate spinal cord injury and promote tissue repair.

Seasonal Diet Composition of Goitered Gazelle (Gazella subgutturosa) in an Arid and Semi-Arid Region of Western China.

Global climate change, habitat fragmentation, and human interference have resulted in a significant, ongoing decline in the population of goitered gazelles. Effective conservation strategies require an understanding of resource requirements of threatened species, such as dietary needs. Therefore, we aimed to elucidate the food composition and seasonal dietary changes of goitered gazelles through microhistological analyses of fresh feces. Fabaceae (11.5%), Gramineae (9.4%), Chenopodiaceae (20.2%), Asteraceae (10.1%), and Rosaceae (19.5%) formed the primary dietary components of goitered gazelle. Additionally, Krascheninnikovia arborescens (13.4%) and Prunus sibirica (16.3%) were identified as the key forage plants. Forbs (50.4%) were the predominant plants for grazing throughout the year, particularly in the spring (72.9%). The proportion of trees in the diet was highest in the autumn (36.7%) and comparatively lower in other seasons. Furthermore, the proportions of shrubs (22.0%) and graminoids (14.8%) both reached their peaks in the winter. Our findings indicate that goitered gazelles strategically forage seasonally to cope with resource bottlenecks, enhancing their adaptability to arid and semi-arid habitats. Our study provides essential ecological information for the conservation of goitered gazelles and emphasizes the importance of dietary studies of species of ecological significance in environmentally sensitive areas.

Immunostimulatory gene therapy combined with checkpoint blockade reshapes tumor microenvironment and enhances ovarian cancer immunotherapy.

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

Nuclear phylogenomics of Asteraceae with increased sampling provides new insights into convergent morphological and molecular evolution.

Convergent morphological evolution is widespread in flowering plants, and understanding this phenomenon relies on well-resolved phylogenies. Nuclear phylogenetic reconstruction using transcriptome datasets has been successful in various angiosperm groups, but it is limited to taxa with available fresh materials. Asteraceae, which are one of the two largest angiosperm families and are important for both ecosystems and human livelihood, show multiple examples of convergent evolution. Nuclear Asteraceae phylogenies have resolved relationships among most subfamilies and many tribes, but many phylogenetic and evolutionary questions regarding subtribes and genera remain, owing to limited sampling. Here, we increased the sampling for Asteraceae phylogenetic reconstruction using transcriptomes and genome-skimming datasets and produced nuclear phylogenetic trees with 706 species representing two-thirds of recognized subtribes. Ancestral character reconstruction supports multiple convergent evolutionary events in Asteraceae, with gains and losses of bilateral floral symmetry correlated with diversification of some subfamilies and smaller groups, respectively. Presence of the calyx-related pappus may have been especially important for the success of some subtribes and genera. Molecular evolutionary analyses support the likely contribution of duplications of MADS-box and TCP floral regulatory genes to innovations in floral morphology, including capitulum inflorescences and bilaterally symmetric flowers, potentially promoting the diversification of Asteraceae. Subsequent divergences and reductions in CYC2 gene expression are related to the gain and loss of zygomorphic flowers. This phylogenomic work with greater taxon sampling through inclusion of genome-skimming datasets reveals the feasibility of expanded evolutionary analyses using DNA samples for understanding convergent evolution.

An in situ forming gel co-loaded with pirarubicin and celecoxib inhibits postoperative recurrence and metastasis of breast cancer.

Surgical removal combined with postoperative chemotherapy is still the mainstay of treatment for most solid tumors. Although chemotherapy reduces the risk of recurrence and metastasis after surgery, it may produce serious adverse effects and impair patient compliance. In situ drug delivery systems are promising tools for postoperative cancer treatment, improving drug delivery efficiency and reducing side effects. Herein, an injectable phospholipid-based in situ forming gel (IPG) was prepared for the co-delivery of antitumor agent pirarubicin (THP) and cyclooxygenase-2 (COX-2) inhibitor celecoxib (CXB) in the surgical incision, and the latter are used extensively in adjuvant chemotherapy for cancer. After injection, the IPG co-loaded with THP and CXB (THP-CXB-IPG) underwent spontaneous phase transition and formed a drug reservoir that fitted the irregular surgical incisions perfectly. In vitro drug release studies and in vivo pharmacokinetic analysis had demonstrated the sustained release behaviors of THP-CXB-IPG. The in vivo therapeutic efficacy was evaluated in mice that had undergone surgical resection of breast cancer, and the THP-CXB-IPG showed considerable inhibition of residual tumor growth after surgery and reduced the incidence of pulmonary metastasis. Moreover, it reduced the systemic toxicity of chemotherapeutic agents. Therefore, THP-CXB-IPG can be a promising candidate for preventing postoperative recurrence and metastasis.

Systemic platelet inhibition with localized chemotherapy by an injectable ROS-scavenging gel against postsurgical breast cancer recurrence and metastasis.

Early solid tumors benefit from surgical resection, but residual stubborn microtumors, pro-inflammatory microenvironment and activated platelets at the postoperative wound site are prone to recurrence and metastasis, resulting in poor prognosis. Here, we developed a dual-pronged strategy consisting of (i) in-situ forming ROS-scavenging gels loaded with anticancer drugs at the postoperative wound site to improve the tumor microenvironment and inhibit the recurrence of residual microtumors after orthotopic surgery, and (ii) systemic administration of clopidegrol via albumin nanoparticles for inhibiting activated platelets in the circulation thus inhibiting tumor remote migration. In a mouse model of postoperative recurrence and metastasis of orthotopic 4T1 breast cancer, the dual-pronged strategy greatly inhibited postoperative orthotopic tumor recurrence and reduced lung metastasis. This work provides an effective strategy for the postoperative intervention and treatment of solid tumors to inhibit postoperative tumor recurrence and metastasis, which has the potential to improve the prognosis and survival of patients with postoperative solid tumors. STATEMENT OF SIGNIFICANCE: Early-stage solid tumors benefit from surgical resection. However, the presence of residual microtumors, pro-inflammatory tumor microenvironment, and activated platelets at the postoperative wound site lead to recurrence and metastasis, ultimately resulting in poor prognosis. Here, we have devised a dual-pronged approach that includes (i) in-situ forming ROS-scavenging gels loaded with anticancer drugs (TM@Gel) at the wound site after surgery to enhance the tumor microenvironment (TME) and hinder the reappearance of residual microtumors, and (ii) systemic administration of clopidegrol through albumin nanoparticles (HHP) for inhibiting activated platelets in the circulation thus impeding tumor distant migration. This work provides a viable option for postoperative intervention and treatment of solid tumors to suppress postoperative tumor recurrence and metastasis.

Distance effect of single atoms on stability of cobalt oxide catalysts for acidic oxygen evolution.

Developing efficient and economical electrocatalysts for acidic oxygen evolution reaction (OER) is essential for proton exchange membrane water electrolyzers (PEMWE). Cobalt oxides are considered promising non-precious OER catalysts due to their high activities. However, the severe dissolution of Co atoms in acid media leads to the collapse of crystal structure, which impedes their application in PEMWE. Here, we report that introducing acid-resistant Ir single atoms into the lattice of spinel cobalt oxides can significantly suppress the Co dissolution and keep them highly stable during the acidic OER process. Combining theoretical and experimental studies, we reveal that the stabilizing effect induced by Ir heteroatoms exhibits a strong dependence on the distance of adjacent Ir single atoms, where the OER stability of cobalt oxides continuously improves with decreasing the distance. When the distance reduces to about 0.6 nm, the spinel cobalt oxides present no obvious degradation over a 60-h stability test for acidic OER, suggesting potential for practical applications.

Dual-Targeting Macrophages and Hepatic Stellate Cells by Modified Albumin Nanoparticles for Liver Cirrhosis Treatment.

Hepatic cirrhosis has become a global public health concern with high mortality and currently lacks effective clinical treatment methods. Activation of hepatic stellate cells (HSCs) and the large number of macrophages infiltrating into the liver play a critical role in the development of liver cirrhosis. This study developed a novel modified nanoparticle system (SRF-CS-PSA NPs) in which Sorafenib (SRF) was encapsulated by palmitic acid-modified albumin (PSA) and further modified with chondroitin sulfate (CS). These modifications enabled the SRF-CS-PSA NPs to effectively target hepatic stellate cells (HSCs) and macrophages. SRF-CS-PSA NPs showed uniform particle size distribution of approximately 120 nm and high loading efficiency of up to 99.5% and can be taken up by HSCs and macrophages via CD44 and SR-A receptors, respectively. In a mouse model of liver cirrhosis, SRF-CS-PSA NPs demonstrated superior targeting and inhibition of HSCs and macrophages, effectively reversing the process of liver cirrhosis. Overall, our study demonstrates the potential of SRF-CS-PSA NPs as a targeted therapy for liver cirrhosis, with promising clinical applications.