Catalytically Active Carbon for Oxygen Reduction Reaction in Energy Conversion: Recent Advances and Future Perspectives.

The shortage and unevenness of fossil energy sources are affecting the development and progress of human civilization. The technology of efficiently converting material resources into energy for utilization and storage is attracting the attention of researchers. Environmentally friendly biomass materials are a treasure to drive the development of new-generation energy sources. Electrochemical theory is used to efficiently convert the chemical energy of chemical substances into electrical energy. In recent years, significant progress has been made in the development of green and economical electrocatalysts for oxygen reduction reaction (ORR). Although many reviews have been reported around the application of biomass-derived catalytically active carbon (CAC) catalysts in ORR, these reviews have only selected a single/partial topic (including synthesis and preparation of catalysts from different sources, structural optimization, or performance enhancement methods based on CAC catalysts, and application of biomass-derived CACs) for discussion. There is no review that systematically addresses the latest progress in the synthesis, performance enhancement, and applications related to biomass-derived CAC-based oxygen reduction electrocatalysts synchronously. This review fills the gap by providing a timely and comprehensive review and summary from the following sections: the exposition of the basic catalytic principles of ORR, the summary of the chemical composition and structural properties of various types of biomass, the analysis of traditional and the latest popular biomass-derived CAC synthesis methods and optimization strategies, and the summary of the practical applications of biomass-derived CAC-based oxidative reduction electrocatalysts. This review provides a comprehensive summary of the latest advances to provide research directions and design ideas for the development of catalyst synthesis/optimization and contributes to the industrialization of biomass-derived CAC electrocatalysis and electric energy storage.

Hemostatic and Ultrasound-Controlled Bactericidal Silk Fibroin Hydrogel via Integrating a Perfluorocarbon Nanoemulsion.

Excessive blood loss and infections are the prominent risks accounting for mortality and disability associated with acute wounds. Consequently, wound dressings should encompass adequate adhesive, hemostatic, and bactericidal attributes, yet their development remains challenging. This investigation presented the benefits of incorporating a perfluorocarbon nanoemulsion (PPP NE) into a silk-fibroin (SF)-based hydrogel. By stimulating the ß-sheet conformation of the SF chains, PPP NEs drastically shortened the gelation time while augmenting the elasticity, mechanical stability, and viscosity of the hydrogel. Furthermore, the integration of PPP NEs improved hemostatic competence by boosting the affinity between cells and biomacromolecules. It also endowed the hydrogel with ultrasound-controlled bactericidal ability through the inducement of inner cavitation by perfluorocarbon and reactive oxygen species (ROS) generated by the sonosensitizer protoporphyrin. Ultimately, we employed a laparotomy bleeding model and a Staphylococcus aureus-infected trauma wound to demonstrate the first-aid efficacy. Thus, our research suggested an emulsion-incorporating strategy for managing emergency wounds.

ADAMTS4 is a crucial proteolytic enzyme for versican cleavage in the amnion at parturition.

Hyalectan cleavage may play an important role in extracellular matrix remodeling. However, the proteolytic enzyme responsible for hyalectan degradation for fetal membrane rupture at parturition remains unknown. Here, we reveal that versican (VCAN) is the major hyalectan in the amnion, where its cleavage increases at parturition with spontaneous rupture of membrane. We further reveal that ADAMTS4 is a crucial proteolytic enzyme for VCAN cleavage in the amnion. Inflammatory factors may enhance VCAN cleavage by inducing ADAMTS4 expression and inhibiting ADAMTS4 endocytosis in amnion fibroblasts. In turn, versikine, the VCAN cleavage product, induces inflammatory factors in amnion fibroblasts, thereby forming a feedforward loop between inflammation and VCAN degradation. Mouse studies show that intra-amniotic injection of ADAMTS4 induces preterm birth along with increased VCAN degradation and proinflammatory factors abundance in the fetal membranes. Conclusively, there is enhanced VCAN cleavage by ADAMTS4 in the amnion at parturition, which can be reenforced by inflammation.

Ovarian ferroptosis induced by androgen is involved in pathogenesis of PCOS.

STUDY QUESTION: Does ovarian ferroptosis play an active role in the development of polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Increased ovarian ferroptosis was present in PCOS ovaries and the inhibition of ferroptosis with ferrostatin-1 (Fer-1) ameliorated polycystic ovary morphology and anovulation. WHAT IS KNOWN ALREADY: Programmed cell death plays a fundamental role in ovarian follicle development. However, the types and mechanisms of cell death involved in the ovary are yet to be elucidated. Ferroptosis is a recently discovered iron-dependent programmed cell death. Impaired iron metabolism and cell death have been observed in women with PCOS, the main cause of anovulatory infertility. Additionally, previous studies reported that an abnormal expression of noncoding RNA may promote ferroptosis in immortalized ovarian granulosa cell lines. However, little is known about whether ovarian ferroptosis is increased in PCOS, and there is insufficient direct evidence for a role of ferroptosis in PCOS, and the underlying mechanism. Moreover, the effect of the inhibition of ferroptosis with Fer-1 in PCOS remains unclear. STUDY DESIGN SIZE DURATION: Ferroptosis was evaluated in human granulosa cells (hGCs) from non-PCOS (n = 6-16) and PCOS (n = 7-18) patients. The experimental study was completed in vitro using primary hGCs from women undergoing IVF. Improvements in PCOS indicators following ferroptosis inhibition with Fer-1 were investigated in a dehydroepiandrosterone (DHEA)-induced PCOS rat model (n = 8 per group). PARTICIPANTS/MATERIALS SETTING METHODS: Ovarian ferroptosis was evaluated in the following ways: by detecting iron concentrations via ELISA and fluorescent probes; measuring malondialdehyde (MDA) concentrations via ELISA; assessing ferroptosis-related protein abundance with western blotting; observing mitochondrial morphology with transmission electron microscopy; and determining cell viability. Primary hGCs were collected from women undergoing IVF. They were treated with dihydrotestosterone (DHT) for 24 h. The effect of DHT on ferroptosis was examined in the presence or absence of small interfering RNA-mediated knockdown of the putative receptor coregulator for signaling molecules. The role of ovarian ferroptosis in PCOS progression was explored in vivo in rats. The DHEA-induced PCOS rat model was treated with the ferroptosis inhibitor, Fer-1, and the oocytes and metaphase II oocytes were counted after ovarian stimulation. Additionally, rats were treated with the ferroptosis inducer, RSL3, to further explore the effect of ferroptosis. The concentrations of testosterone, FSH, and LH were assessed. MAIN RESULTS AND THE ROLE OF CHANCE: Increased ferroptosis was detected in the ovaries of patients with PCOS and in rats with DHEA-induced PCOS. Increased concentrations of Fe2+ (P < 0.05) and MDA (P < 0.05), and upregulated nuclear receptor coactivator 4 protein levels, and downregulated ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4) proteins were observed in the hGCs in patients with PCOS and ovaries of PCOS rats (P < 0.05 versus control). DHT was shown to induce ferroptosis via activation of NOCA4-dependent ferritinophagy. The inhibition of ferroptosis with Fer-1 in rats ameliorated a cluster of PCOS traits including impaired glucose tolerance, irregular estrous cycles, reproductive hormone dysfunction, hyperandrogenism, polycystic ovaries, anovulation, and oocyte quality (P < 0.05). Treating rats with RSL3 resulted in polycystic ovaries and hyperandrogenism (P < 0.05). LARGE-SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: Although ovarian-targeted ferroptosis inhibition may be a more targeted treatment for PCOS, the underlying mechanisms in the cycle between ferroptosis and hyperandrogenism require further exploration. Additionally, since PCOS shows high heterogeneity, it is important to investigate whether ferroptosis increases are present in all patients with PCOS. WIDER IMPLICATIONS OF THE FINDINGS: Androgen-induced ovarian ferroptosis appears to play a role in the pathogenesis of PCOS, which potentially makes it a promising treatment target in PCOS. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the National Key R&D Program of China (2023YFC2705500, 2023YFC2705505, 2019YFA0802604), National Natural Science Foundation of China (No. 82130046, 82320108009, 82101708, 82101747, and 82001517), Shanghai leading talent program, Innovative research team of high-level local universities in Shanghai (No. SHSMU-ZLCX20210201, No. SSMU-ZLCX20180401), Shanghai Jiaotong University School of Medicine, Affiliated Renji Hospital Clinical Research Innovation Cultivation Fund Program (RJPY-DZX-003) and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (No. 20161413), Shanghai's Top Priority Research Center Construction Project (2023ZZ02002), and Three-Year Action Plan for Strengthening the Construction of the Public Health System in Shanghai (GWVI-11.1-36). The authors report no competing interests.

Construction of Ni/In2O3 Integrated Nanocatalysts Based on MIL-68(In) Precursors for Efficient CO2 Hydrogenation to Methanol.

The efficient and economic conversion of CO2 and renewable H2 into methanol has received intensive attention due to growing concern for anthropogenic CO2 emissions, particularly from fossil fuel combustion. Herein, we have developed a novel method for preparing Ni/In2O3 nanocatalysts by using porous MIL-68(In) and nickel(II) acetylacetonate (Ni(acac)2) as the dual precursors of In2O3 and Ni components, respectively. Combined with in-depth characterization analysis, it was revealed that the utilization of MIL-68(In) as precursors favored the good distribution of Ni nanoparticles (∼6.2 nm) on the porous In2O3 support and inhibited the metal sintering at high temperatures. The varied catalyst fabrication parameters were explored, indicating that the designed Ni/In2O3 catalyst (Ni content of 5 wt %) exhibited better catalytic performance than the compared catalyst prepared using In(OH)3 as a precursor of In2O3. The obtained Ni/In2O3 catalyst also showed excellent durability in long-term tests (120 h). However, a high Ni loading (31 wt %) would result in the formation of the Ni-In alloy phase during the CO2 hydrogenation which favored CO formation with selectivity as high as 69%. This phenomenon is more obvious if Ni and In2O3 had a strong interaction, depending on the catalyst fabrication methods. In addition, with the aid of in situ diffuse reflectance infrared Fourier transform spectroscopy and density functional theory (DFT) calculations, the Ni/In2O3 catalyst predominantly follows the formate pathway in the CO2 hydrogenation to methanol, with HCOO* and *H3CO as the major intermediates, while the small size of Ni particles is beneficial to the formation of formate species based on DFT calculation. This study suggests that the Ni/In2O3 nanocatalyst fabricated using metal-organic frameworks as precursors can effectively promote CO2 thermal hydrogenation to methanol.

Fe, N-Inducing Interfacial Electron Redistribution in NiCo Spinel on Biomass-Derived Carbon for Bi-functional Oxygen Conversion.

Herein, an interfacial electron redistribution is proposed to boost the activity of carbon-supported spinel NiCo2O4 catalyst toward oxygen conversion via Fe, N-doping strategy. Fe-doping into octahedron induces a redistribution of electrons between Co and Ni atoms on NiCo1.8Fe0.2O4@N-carbon. The increased electron density of Co promotes the coordination of water to Co sites and further dissociation. The generation of proton from water improves the overall activity for the oxygen reduction reaction (ORR). The increased electron density of Ni facilitates the generation of oxygen vacancies. The Ni-VO-Fe structure accelerates the deprotonation of *OOH to improve the activity toward oxygen evolution reaction (OER). N-doping modulates the electron density of carbon to form active sites for the adsorption and protonation of oxygen species. Fir wood-derived carbon endows catalyst with an integral structure to enable outstanding electrocatalytic performance. The NiCo1.8Fe0.2O4@N-carbon express high half-wave potential up to 0.86 V in ORR and low overpotential of 270 mV at 10 mA cm-2 in OER. The zinc-air batteries (ZABs) assembled with the as-prepared catalyst achieve long-term cycle stability (over 2000 cycles) with peak power density (180 mWcm-2). Fe, N-doping strategy drives the catalysis of biomass-derived carbon-based catalysts to the highest level for the oxygen conversion in ZABs.

ALYREF-JunD-SLC7A5 axis promotes pancreatic ductal adenocarcinoma progression through epitranscriptome-metabolism reprogramming and immune evasion.

Pancreatic ductal adenocarcinoma (PDAC) is a kind of tumor lacking nutrients due to its poor vascularity and desmoplasia. Recent studies have shown that cancer cells might achieve growth advantage through epitranscriptome reprogramming. However, the role of m5C in PDAC was not fully understood. We found that Aly/REF export factor (ALYREF), a reader of m5C modification, was overexpressed in PDAC, and associated with bad prognosis. In addition, the ALYREF expression was negatively related to CD8+ T cells infiltration in clinical samples. ALYREF knockdown decreased tumor growth in vivo partly dependent of immunity. ALYREF silencing decreased SLC7A5 expression and subsequently inactivated mTORC1 pathway, resulting in decreased tumor proliferation. Mechanically, ALYREF specifically recognized m5C sites in JunD mRNA, maintained the stabilization of JunD mRNA and subsequently upregulated transcription of SLC7A5. Since SLC7A5 was a key transporter of large neutral amino acids (LNAAs), overexpression of SLC7A5 on tumor cells depleted amino acid in microenvironment and restricted CD8+ T cells function. Moreover, ALYREF-JunD-SLC7A5 axis was overexpressed and negatively related with survival through TMA assays. In conclusion, this research revealed the relationship between m5C modification, amino acid transportation and immune microenvironment. ALYREF might be a novel target for PDAC metabolic vulnerability and immune surveillance.

Biomass-Derived Catalytically Active Carbon Materials for the Air Electrode of Zn-air Batteries.

Given the growing environmental and energy problems, developing clean, renewable electrochemical energy storage devices is of great interest. Zn-air batteries (ZABs) have broad prospects in energy storage because of their high specific capacity and environmental friendliness. The unavailability of cheap air electrode materials and effective and stable oxygen electrocatalysts to catalyze air electrodes are main barriers to large-scale implementation of ZABs. Due to the abundant biomass resources, self-doped heteroatoms, and unique pore structure, biomass-derived catalytically active carbon materials (CACs) have great potential to prepare carbon-based catalysts and porous electrodes with excellent performance for ZABs. This paper reviews the research progress of biomass-derived CACs applied to ZABs air electrodes. Specifically, the principle of ZABs and the source and preparation method of biomass-derived CACs are introduced. To prepare efficient biomass-based oxygen electrocatalysts, heteroatom doping and metal modification were introduced to improve the efficiency and stability of carbon materials. Finally, the effects of electron transfer number and H2 O2 yield in ORR on the performance of ZABs were evaluated. This review aims to deepen the understanding of the advantages and challenges of biomass-derived CACs in the air electrodes of ZABs, promote more comprehensive research on biomass resources, and accelerate the commercial application of ZABs.

An Oxidoreductase-like Protein is Required for Verticillium dahliae Infection and Participates in the Metabolism of Host Plant Defensive Compounds.

Verticillium dahliae, a notorious phytopathogenic fungus, is responsible for vascular wilt diseases in numerous crops. Uncovering the molecular mechanisms underlying pathogenicity is crucial for controlling V. dahliae. Herein, we characterized a putative oxidoreductase-like protein (VdOrlp) from V. dahliae that contains a functional signal peptide. While the expression of VdOrlp was low in artificial media, it significantly increased during host infection. Deletion of VdOrlp had minimal effects on the growth and development of V. dahliae but severely impaired its pathogenicity. Metabolomic analysis revealed significant changes in organic heterocyclic compounds and phenylpropane compounds in cotton plants infected with ΔVdOrlp and V991. Furthermore, VdOrlp expression was induced by lignin, and its deletion affected the metabolism of host lignin and phenolic acids. In conclusion, our results demonstrated that VdOrlp plays an important role in the metabolism of plant phenylpropyl lignin and organic heterocyclic compounds and is required for fungal pathogenicity in V. dahliae.

Attenuation of palmitic acid-induced lysyl oxidase overexpression in the ovary contributes to the improvement of ovulation in obesity by metformin.

STUDY QUESTION: Does palmitic acid (PA), the most common saturated free fatty acid (FFA) in individuals with obesity, contribute to anovulation through upregulation of the collagen-crosslinking enzyme lysyl oxidase (LOX) in the ovary? SUMMARY ANSWER: Increased PA in individuals with obesity can cause LOX upregulation via the activation of hypoxia-inducible factor-1α (HIF-1α), resulting in abnormal collagen deposition in the ovary and anovulation, which can be ameliorated by metformin therapy. WHAT IS KNOWN ALREADY: The underlying cause of anovulation in individuals with obesity is poorly defined, and accumulating evidence indicates that hormonal disturbance, insulin resistance, and inflammation may all play a role in the development of ovulation disorders in individuals with obesity. However, it remains to be determined whether PA plays a role in the regulation of LOX expression, thus disrupting ovarian extracellular matrix (ECM) remodelling in the ovary and resulting in impaired ovulation in individuals with obesity. STUDY DESIGN SIZE DURATION: PA concentration and LOX protein abundance and activity in follicular fluid and ovarian tissue were compared between control (n = 21) subjects, patients with obesity with ovulation (n = 22), and patients with obesity with anovulation (n = 16). The effect of PA on LOX protein expression, and the underlying mechanism, was examined in primary human granulosa cells in vitro. The improvements in obesity conditions induced by LOX inhibition combined with metformin were investigated in a high-fat diet-induced obese rat model. PARTICIPANTS/MATERIALS SETTING METHODS: The abundance of PA concentration and LOX activity was measured via a LOX activity assay and ELISA, respectively. The effect of PA on LOX protein expression was examined in the presence or absence of inhibitors of signalling molecules and siRNA-mediated knockdown of the putative transcription factor. Chromatin immunoprecipitation assays were subsequently conducted to further identify the responsible transcription factor. The role of metformin in the treatment of anovulation by LOX inhibition was investigated in a high-fat diet (HFD)-induced obese rat model. The numbers of retrieved total oocytes and metaphase II oocytes were recorded upon ovarian stimulation. Masson's trichrome staining was used to measure the total collagen content, and immunohistochemical staining and western blotting were used to measure LOX, HIF-1α, and collagen I and IV in the ovary. MAIN RESULTS AND THE ROLE OF CHANCE: Significantly increased FFA, LOX, and collagen abundance were observed in the ovaries of obese women with anovulation, compared to healthy controls or obese women with ovulation. In a HFD-induced obese rat model, metformin corrected the distortion of ovarian morphology by decreasing LOX and collagen protein abundance in the ovary and improving oestrous cyclicity and ovulation. PA increased LOX expression via the activation of HIF-1α in human granulosa cells, which was attenuated by metformin. LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: Several other saturated and polyunsaturated FFAs, such as stearic acid and arachidonic acid, are also increased in the blood of individuals with obesity, and increased levels of other FFAs may also contribute to the development of anovulation in individuals with obesity, which needs to be further verified in the future. WIDER IMPLICATIONS OF THE FINDINGS: Elevated PA in individuals with obesity can cause LOX dysregulation via activation of HIF-1α, resulting in abnormal collagen deposition in the ovary and anovulation. This dysregulation can be ameliorated by metformin therapy through its local effect on ECM remodelling in the ovary, which is independent of its systemic effect on insulin sensitivity and chronic inflammation. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Natural Science Foundation of China (grant numbers 82101730, 82130046, and 31900598) and Innovative Research Team of High-level local Universities in Shanghai (SHSMU-ZLCX20210201). All the authors declare no conflicts of interest in relation to this work.

Boron difluoride modified zinc metal-organic framework-based "off-on" fluorescence sensor for tetracycline and Al3+ detection.

A novel fluorescence "off-on" probe was developed using a boron difluoride-modified zinc metal-organic framework (Zn-MOF3) for sensitive determination of tetracycline (TC) and Al3+. The Zn-MOF3 has excellent optical property and good applicability in aqueous phase. The fluorescence recorded at 436 nm was quenched at the excitation wavelength of 336 nm. Signal-off detection of tetracycline via fluorescence quenching of Zn-MOF3 is based on the inner filter effect. Fluorescence on-off-on detection of Al3+ occurs via the specific binding between tetracycline and Al3+. The limits of detection for TC and Al3+ were 28.4 nM and 106.7 nM, respectively. This probe exhibited high selectivity which was used for the determination of TC and Al3+ with satisfied recoveries (89.8 to 105.6% for TC, 90.0 to 110.4% for Al3+) and good precision (< 5%) in milk. The developed sensor represents the first "off-on" system for fluorescence detection of TC and Al3+ based on Zn-MOF3 with a better aspect of the innovation.

Type II collagen scaffolds repair critical-sized osteochondral defects under induced conditions of osteoarthritis in rat knee joints via inhibiting TGF-ß-Smad1/5/8 signaling pathway.

The bidirectional relationship between osteochondral defects (OCD) and osteoarthritis (OA), with each condition exacerbating the other, makes OCD regeneration in the presence of OA challenging. Type II collagen (Col2) is important in OCD regeneration and the management of OA, but its potential applications in cartilage tissue engineering are significantly limited. This study investigated the regeneration capacity of Col2 scaffolds in critical-sized OCDs under surgically induced OA conditions and explored the underlying mechanisms that promoted OCD regeneration. Furthermore, the repair potential of Col2 scaffolds was validated in over critical-sized OCD models. After 90 days or 150 days since scaffold implantation, complete healing was observed histologically in critical-sized OCD, evidenced by the excellent integration with surrounding native tissues. The newly formed tissue biochemically resembled adjacent natural tissue and exhibited comparable biomechanical properties. The regenerated OA tissue demonstrated lower expression of genes associated with cartilage degradation than native OA tissue but comparable expression of genes related to osteochondral anabolism compared with normal tissue. Additionally, transcriptome and proteome analysis revealed the hindrance of TGF-ß-Smad1/5/8 in regenerated OA tissue. In conclusion, the engrafting of Col2 scaffolds led to the successful regeneration of critical-sized OCDs under surgically induced OA conditions by inhibiting the TGF-ß-Smad1/5/8 signaling pathway.

Investigating the anti-atherosclerotic effects and potential mechanism of Dalbergia odorifera in ApoE-deficient mice using network pharmacology combined with metabolomics.

Dalbergia odorifera (DO) is a precious rosewood species in Southern Asia, and its heartwood is used in China as an official plant for invigorating blood circulation and eliminating stasis. This study aims to evaluate the efficacy of DO on atherosclerosis (AS), and further explore its active components and potential mechanisms. The apolipoprotein-E (ApoE)-deficient mice fed a high-fat diet were used as model animals, and the pathological changes in mice with or without DO treatment were compared to evaluate the pharmacodynamics of DO on AS. The mechanisms were preliminarily expounded by combining with metabolomics and network pharmacology. Moreover, the bioactive components and targets were assessed by cell experiments and molecular docking, respectively. Our findings suggested that DO significantly modulated blood lipid levels and alleviated intimal hyperplasia in atherosclerotic-lesioned mice, and the mechanisms may involve the regulation of 18 metabolites that changed during the progression of AS, thus affecting 3 major metabolic pathways and 3 major signaling pathways. Moreover, the interactions between 16 compounds with anti-proliferative effect and hub targets in the 3 signaling pathways were verified using molecular docking. Collectively, our findings preliminarily support the therapeutic effect of DO in atherosclerosis, meanwhile explore the active constituents and potential pharmacological mechanisms, which is conducive to its reasonable exploitation and utilization.

Targeting cancer-associated fibroblast autophagy renders pancreatic cancer eradicable with immunochemotherapy by inhibiting adaptive immune resistance.

Accumulating evidence suggests that cancer-associated fibroblast (CAF) macroautophagy/autophagy is crucial in tumor development and may be a therapeutic target for pancreatic ductal adenocarcinoma (PDAC). However, the role of CAF autophagy during immune surveillance and cancer immunotherapy is unclear. The present study revealed that the inhibition of CAF autophagy suppresses in vivo tumor development in immune-deficient xenografts. This deletion compromises anti-tumor immunity and anti-tumor efficacy both in vitro and in vivo by upregulating CD274/PDL1 levels in an immune-competent mouse model. A block in CAF autophagy reduced the production of IL6 (interleukin 6), disrupting high desmoplastic TME and decreasing USP14 expression at the transcription level in pancreatic cancer cells. We further identify USP14 as the post-translational factor responsible for downregulating CD274 expression by removing K63 linked-ubiquitination at the K280 residue. Finally, chloroquine diphosphate-loaded mesenchymal stem cell (MSC)-liposomes, by accurately targeting CAFs, inhibited CAF autophagy, improving the efficacy of immunochemotherapy to combat pancreatic cancer.Abbreviation: AIR: adaptive immune resistance; ATRA: all-trans-retinoicacid; CAF: cancer-associated fibroblast; CD274/PDL1: CD274 molecule; CM: conditioned medium; CQ: chloroquine diphosphate; CyTOF: Mass cytometry; FGF2/bFGF: fibroblast growth factor 2; ICB: immune checkpoint blockade; IF: immunofluorescence; IHC: immunohistochemistry; IP: immunoprecipitation; MS: mass spectrometer; MSC: mesenchymal stem cell; PDAC: pancreatic ductal adenocarcinoma; TEM: transmission electron microscopy; TILs: tumor infiltrating lymphocytes; TME: tumor microenvironment; USP14: ubiquitin specific peptidase 14.

Manipulating the Spin State of Co Sites in Metal-Organic Frameworks for Boosting CO2 Photoreduction.

Photocatalytic CO2 reduction holds great potential for alleviating global energy and environmental issues, where the electronic structure of the catalytic center plays a crucial role. However, the spin state, a key descriptor of electronic properties, is largely overlooked. Herein, we present a simple strategy to regulate the spin states of catalytic Co centers by changing their coordination environment by exchanging the Co species into a stable Zn-based metal-organic framework (MOF) to afford Co-OAc, Co-Br, and Co-CN for CO2 photoreduction. Experimental and DFT calculation results suggest that the distinct spin states of the Co sites give rise to different charge separation abilities and energy barriers for CO2 adsorption/activation in photocatalysis. Consequently, the optimized Co-OAc with the highest spin-state Co sites presents an excellent photocatalytic CO2 activity of 2325.7 µmol·g-1·h-1 and selectivity of 99.1% to CO, which are among the best in all reported MOF photocatalysts, in the absence of a noble metal and additional photosensitizer. This work underlines the potential of MOFs as an ideal platform for spin-state manipulation toward improved photocatalysis.

Infiltrating Perfluorocarbon Nanoemulsion and Sensitizing Ultrasound Cavitation to Eradicate Biofilms.

Developing strategies for the treatment of bacterial biofilms is challenging due to their complex and resilient structure, low permeability to therapeutics, and ability to protect resident pathogens. Herein, we demonstrate that a polylysine-stabilized perfluorocarbon nanoemulsion is favored for penetrating biofilms and sensitizing the cavitation effect of low-intensity ultrasound, resulting in the dispersal of extracellular polymeric substances and killing of the protected cells. Through experiments, we observed a complete penetration of the nanoemulsion in a 40 µm Pseudomonas aeruginosa biofilm and demonstrated that it was induced by the fluidic perfluorocarbon, possibly attributing to its low surface tension. Furthermore, we presented an almost complete antibiofilm effect with a low-intensity ultrasound (1 MHz, 0.75 W/cm2, 5 min) in diverse cases, including cultured biofilms, colonized urinary catheters, and chronic wounds. During the treatment process, the perfluorocarbon phase enhanced the number and imploding energy of ultrasound cavities, thoroughly divided the biofilm structure, prevented biofilm self-healing, and sterilized the resident pathogens. Thus, the penetration and sensitization of the nanoemulsion might serve as a facile and potent strategy for eradicating biofilms in various applications.

Precise Design and Modification Engineering of Single-Atom Catalytic Materials for Oxygen Reduction.

Due to their unique electronic and structural properties, single-atom catalytic materials (SACMs) hold great promise for the oxygen reduction reaction (ORR). Coordinating environmental and engineering strategies is the key to improving the ORR performance of SACMs. This review summarizes the latest research progress and breakthroughs of SACMs in the field of ORR catalysis. First, the research progress on the catalytic mechanism of SACMs acting on ORR is reviewed, including the latest research results on the origin of SACMs activity and the analysis of pre-adsorption mechanism. The study of the pre-adsorption mechanism is an important breakthrough direction to explore the origin of the high activity of SACMs and the practical and theoretical understanding of the catalytic process. Precise coordination environment modification, including in-plane, axial, and adjacent site modifications, can enhance the intrinsic catalytic activity of SACMs and promote the ORR process. Additionally, several engineering strategies are discussed, including multiple SACMs, high loading, and atomic site confinement. Multiple SACMs synergistically enhance catalytic activity and selectivity, while high loading can provide more active sites for catalytic reactions. Overall, this review provides important insights into the design of advanced catalysts for ORR.

Photoacoustic Imaging Endometriosis Lesions with Nanoparticulate Polydopamine as a Contrast Agent.

Endometriosis (EM) is a prevalent and debilitating gynecological disorder primarily affecting women of reproductive age. The diagnosis of EM is historically hampered by delays, owing to the absence of reliable diagnostic and monitoring techniques. Herein, it is reported that photoacoustic imaging can be a noninvasive modality for deep-seated EM by employing a hyaluronic-acid-modified polydopamine (PDA@HA) nanoparticle as the contrast agent. The PDA@HA nanoparticles exhibit inherent absorption and photothermal effects when exposed to near-infrared light, proficiently converting thermal energy into sound waves. Leveraging the targeting properties of HA, distinct photoacoustic signals emanating from the periphery of orthotopic EM lesions are observed. These findings are corroborated through anatomical observations and in vivo experiments involving mice with green fluorescent protein-labeled EM lesions. Moreover, the changes in photoacoustic intensity over a 24 h period reflect the dynamic evolution of PDA@HA nanoparticle biodistribution. Through the utilization of a photoacoustic ultrasound modality, in vivo assessments of EM lesion volumes are conducted. This innovative approach not only facilitates real-time monitoring of the therapeutic kinetics of candidate drugs but also obviates the need for the sacrifice of experimental mice. As such, this study presents a promising avenue for enhancing the diagnosis and drug-screening processes of EM.

Point-of-care ultrasound as a diagnostic tool in respiratory assessment in awake paediatric patients: a comparative study.

BACKGROUND: Chest X-ray (CXR) has typically been the main investigation in children with suspected respiratory pathology. Recent advances in lung point-of-care ultrasound (POCUS) have shown the potential for it to be comparative, if not better, than CXR. The objective of this study was to compare CXR with lung POCUS in children with respiratory illness in a ward-based setting at a paediatric teaching hospital. METHODS: Any child <18 years of age presenting to Southampton Children's Hospital requiring a CXR for clinical reasons also had lung POCUS performed. CXR was reported by a consultant paediatric radiologist and lung POCUS was reviewed retrospectively by a blinded POCUS clinician, with only the clinical information provided on the CXR request. Comparisons were made between the CXR and lung POCUS findings. RESULTS: 100 paired lung POCUS and CXR were included in the study. 30% of lung POCUS were normal with 97% of these having a normal CXR. 70% of cases had POCUS abnormalities with 96% of POCUS cases identifying comparative lung pathology. Lung POCUS therefore had a sensitivity of 98.51% and a specificity of 87.9% with a diagnostic accuracy of 95% when compared with the CXR report. CONCLUSIONS: Lung POCUS has excellent diagnostic accuracy. The diagnosis of normal lung on POCUS when performed by a trained practitioner can reliably reduce the need for a CXR, thus reducing CXR use and radiation exposure in children. An abnormal lung POCUS could then either give the diagnosis or lead to a CXR with the expectation of clinically relevant findings.

Nano-Emulsified Perfluorooctyl Bromide Can Infiltrate Gram-Negative Bacteria and Sensitize Them to Ultrasound.

Gram-negative (G-) bacterial infections remain one of the most urgent global health threats, because the distinctive envelope structure hinders the penetration of therapeutics. Here, we showed that a perfluorooctyl bromide nanoemulsion (PFOB NE) uniquely interacts with G- bacteria. After cell envelope attachment, the PFOB can infiltrate the cell and was diffused throughout. In this process, it impaired the membranes by disintegrating phospholipid molecules, enhancing the consequent ultrasonic cavitation to break the envelope. We identified through ultrasound that the NE had remarkable bactericidal effects against various antibiotic-resistant pathogens. Using in situ sterilization, this approach accelerated the recovery of bacteria-infected murine skin wounds. Thus, combining PFOB and ultrasound might be an alternative tool for conquering the growing threat of G- pathogens.