Lactylated Apolipoprotein C-II Induces Immunotherapy Resistance by Promoting Extracellular Lipolysis.

Mortality rates due to lung cancer are high worldwide. Although PD-1 and PD-L1 immune checkpoint inhibitors boost the survival of patients with non-small-cell lung cancer (NSCLC), resistance often arises. The Warburg Effect, which causes lactate build-up and potential lysine-lactylation (Kla), links immune dysfunction to tumor metabolism. The role of non-histone Kla in tumor immune microenvironment and immunotherapy remains to be clarified. Here, global lactylome profiling and metabolomic analyses of samples from patients with NSCLC is conducted. By combining multi-omics analysis with in vitro and in vivo validation, that intracellular lactate promotes extracellular lipolysis through lactyl-APOC2 is revealed. Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis. Moreover, the anti-APOC2K70-lac antibody that sensitized anti-PD-1 therapy in vivo is developed. This findings highlight the potential of anti lactyl-APOC2-K70 approach as a new combination therapy for sensitizing immunotherapeutic responses.

The transcriptome of MHV-infected RAW264.7 cells offers an alternative model for macrophage innate immunity research.

BACKGROUND: Macrophages are the primary innate immune cells encountered by the invading coronaviruses, and their abilities to initiate inflammatory reactions, to maintain the immunity homeostasis by differential polarization, to train the innate immune system by epigenic modification have been reported in laboratory animal research. METHODS: In the current in vitro research, murine macrophage RAW 264.7 cell were infected by mouse hepatitis virus, a coronavirus existed in mouse. At 3-, 6-, 12-, 24-, and 48-h post infection (hpi.), the attached cells were washed with PBS and harvested in Trizol reagent. Then The harvest is subjected to transcriptome sequencing. RESULTS: The transcriptome analysis showed the immediate (3 hpi.) up regulation of DEGs related to inflammation, like Il1b and Il6. DEGs related to M2 differential polarization, like Irf4 showed up regulation at 24 hpi., the late term after viral infection. In addition, DEGs related to metabolism and histone modification, like Ezh2 were detected, which might correlate with the trained immunity of macrophages. CONCLUSIONS: The current in vitro viral infection study showed the key innated immunity character of macrophages, which suggested the replacement value of viral infection cells model, to reduce the animal usage in preclinical research.

Mechanism and therapeutic targets of the involvement of a novel lysosomal proton channel TMEM175 in Parkinson's disease.

Parkinson's disease (PD), recognized as the second most prevalent neurodegenerative disease in the aging population, presents a significant challenge due to the current lack of effective treatment methods to mitigate its progression. Many pathogenesis of PD are related to lysosomal dysfunction. Moreover, extensive genetic studies have shown a significant correlation between the lysosomal membrane protein TMEM175 and the risk of developing PD. Building on this discovery, TMEM175 has been identified as a novel potassium ion channel. Intriguingly, further investigations have found that potassium ion channels gradually close and transform into hydrion "excretion" channels in the microenvironment of lysosomes. This finding was further substantiated by studies on TMEM175 knockout mice, which exhibited pronounced motor dysfunction in pole climbing and suspension tests, alongside a notable reduction in dopamine neurons within the substantia nigra compacta. Despite these advancements, the current research landscape is not without its controversies. In light of this, the present review endeavors to methodically examine and consolidate a vast array of recent literature on TMEM175. This comprehensive analysis spans from the foundational research on the structure and function of TMEM175 to expansive population genetics studies and mechanism research utilizing cellular and animal models.A thorough understanding of the structure and function of TMEM175, coupled with insights into the intricate mechanisms underpinning lysosomal dysfunction in PD dopaminergic neurons, is imperative. Such knowledge is crucial for pinpointing precise intervention targets, thereby paving the way for novel therapeutic strategies that could potentially alter the neurodegenerative trajectory of PD.

Regional Functionalization Molecular Design Strategy: A Key to Enhancing the Efficiency of Multi-Resonance OLEDs.

Herein, we propose a regional functionalization molecular design strategy that enables independent control of distinct pivotal parameters through distinct segments of the molecule. Three novel blue emitters A-BN, DA-BN, and A-DBN, have been successfully synthesized by integrating highly rigid and three-dimensional adamantane-containing spirofluorene units into the MR framework. These molecules form two distinctive functional parts: part 1 comprises a boron-nitrogen (BN)-MR framework with adjacent benzene and fluorene units forming a central luminescent core characterized by an exceptionally rigid planar geometry, allowing for narrow FWHM values; part 2 includes peripheral mesitylene, benzene, and adamantyl groups, creating a unique three-dimensional "umbrella-like" conformation to mitigate intermolecular interactions and suppress exciton annihilation. The resulting A-BN, DA-BN, and A-DBN exhibit remarkably narrow FWHM values ranging from 18 to 14 nm and near-unity photoluminescence quantum yields. Particularly, OLEDs based on DA-BN and A-DBN demonstrate outstanding efficiencies of 35.0% and 34.3%, with FWHM values as low as 22 nm and 25 nm, respectively, effectively accomplishing the integration of high color purity and high device performance.

Transcriptome study reveals tick immune genes restrict Babesia microti infection.

A systems biology approach was employed to gain insight into tick biology and interactions between vectors and pathogens. Haemaphysalis longicornis serves as one of the primary vectors of Babesia microti, significantly impacting human and animal health. Obtaining more information about their relationship is crucial for a comprehensive understanding of tick and pathogen biology, pathogen transmission dynamics, and potential control strategies. RNA sequencing of uninfected and B. microti-infected ticks resulted in the identification of 15 056 unigenes. Among these, 1 051 were found to be differentially expressed, with 796 being upregulated and 255 downregulated (P < 0.05). Integrated transcriptomics datasets revealed the pivotal role of immune-related pathways, including the Toll, Janus kinase/signal transducer and activator of transcription (JAK-STAT), immunodeficiency, and RNA interference (RNAi) pathways, in response to infection. Consequently, 3 genes encoding critical transcriptional factor Dorsal, Relish, and STAT were selected for RNAi experiments. The knockdown of Dorsal, Relish, and STAT resulted in a substantial increase in Babesia infection levels compared to the respective controls. These findings significantly advanced our understanding of tick-Babesia molecular interactions and proposed novel tick antigens as potential vaccine targets against tick infestations and pathogen transmission.

Optimizing the energy level alignment for achieving record-breaking efficiency in hot exciton deep red OLEDs.

To effectively compete with the quenching process in long-wavelength regions like deep red (DR) and near-infrared (NIR), rapid radiative decay is urgently needed to address the challenges posed by the "energy gap law". Herein, we confirmed that it is crucial for hot exciton emitters to attain a narrow energy gap (ΔES1-T2) between the lowest singlet excited (S1) state and second triplet excited (T2) state, while ensuring that T2 slightly exceeds S1 in the energy level. Two proofs-of-concept of hot exciton DR emitters, namely αT-IPD and ßT-IPD, were successfully designed and synthesized by coupling electron-acceptors N,N-diphenylnaphthalen-2-amine (αTPA) and N,N-diphenylnaphthalen-1-amine (ßTPA) with an electron-withdrawing unit 5-(4-(tert-butyl) phenyl)-5H-pyrazino[2,3-b]indole-2,3-dicarbonitrile (IPD). Both emitters exhibited a narrow ΔES1-T2, with T2 being slightly higher than S1. Additionally, both emitters showed significantly large ΔET2-T1. Moreover, due to their aggregation-induced emission characteristics, J-aggregated packing modes, moderate strength intermolecular CN⋯H-C and C-H⋯π interactions, and unique, comparatively large center-to-center distances among trimers in the crystalline state, both αT-IPD and ßT-IPD emitters exhibited remarkable photoluminescence quantum yields of 68.5% and 73.5%, respectively, in non-doped films. Remarkably, the corresponding non-doped DR-OLED based on ßT-IPD achieved a maximum external quantum efficiency of 15.5% at an emission peak wavelength of 667 nm, representing the highest reported value for hot exciton DR-OLEDs.

Bletilla striata polysaccharide-coated andrographolide nanomicelles for targeted drug delivery to enhance anti-colon cancer efficacy.

Background: Vitamin E, which is also known as tocopherol, is a compound with a polyphenol structure. Its esterified derivative, Vitamin E succinate (VES), exhibits unique anticancer and healthcare functions as well as immunomodulatory effects. Natural polysaccharides are proved to be a promising material for nano-drug delivery systems, which show excellent biodegradability and biocompatibility. In this study, we employed a novel bletilla striata polysaccharide-vitamin E succinate polymer (BSP-VES) micelles to enhance the tumor targeting and anti-colon cancer effect of andrographolide (AG). Methods: BSP-VES polymer was synthesized through esterification and its structure was confirmed using 1H NMR. AG@BSP-VES was prepared via the dialysis method and the drug loading, entrapment efficiency, stability, and safety were assessed. Furthermore, the tumor targeting ability of AG@BSP-VES was evaluated through targeted cell uptake and in vivo imaging. The antitumor activity of AG@BSP-VES was measured in vitro using MTT assay, Live&Dead cell staining, and cell scratch test. Results: In this study, we successfully loaded AG into BSP-VES micelles (AG@BSP-VES), which exhibited good stability, biosafety and sustained release effect. In addition, AG@BSP-VES also showed excellent internalization capability into CT26 cells compared with NCM460 cells in vitro. Meanwhile, the specific delivery of AG@BSP-VES micelles into subcutaneous and in-situ colon tumors was observed compared with normal colon tissues in vivo during the whole experiment process (1-24 h). What's more, AG@BSP-VES micelles exhibited significant antitumor activities than BSP-VES micelles and free AG. Conclusion: The study provides a meaningful new idea and method for application in drug delivery system and targeted treatment of colon cancer based on natural polysaccharides.

Reshaping the root endophytic microbiota in plants to combat mercury-induced stress.

Emerging evidence suggests that plants experiencing abiotic stress actively seek help from soil microbes. However, the empirical evidence supporting this strategy is limited, especially in response to heavy metal stress. We used integrated microbial community profiling and culture-based methods to investigate the interaction between mercury (Hg) stress, the entophytic root microbiome, and maize seedlings. The results of the pot experiment showed that soil Hg (20 mg/kg) strongly inhibited maize growth, indicating its strong phytotoxicity. Furthermore, Hg stress significantly altered the structure of the bacterial and fungal communities and enriched the potentially pathogenic Fusarium sp., suggesting that soil Hg stress may enhance the bio-stress induced by Fusarium species in maize. Additionally, soil Hg also led to the enrichment of beneficial bacterial members of Streptomyces, Lysobacter, and Sphingomonas (defined as differential species), which were also identified as keystone species in the Hg treatment by the analysis of co-occurrence networks. Therefore, it can be postulated that the members of Streptomyces, Lysobacter, and Sphingomonas function as stress-alleviating microbes. We successfully isolated the representatives of these stress-alleviating microbes. As expected, these strains mitigated the detrimental effects of Hg stess for the maize seedlings, suggesting that plants recruit the stress-alleviated microbiota to combat Hg stress. This study provides insights into the potential of manipulating the root microbiome to enhance plant growth in polluted environments.

A Hydrogen-Bonded Organic Framework-Based Mitochondrion-Targeting Bioorthogonal Platform for the Modulation of Mitochondrial Epigenetics.

Bioorthogonal chemistry represents a powerful tool in chemical biology, which shows great potential in epigenetic modulation. As a proof of concept, the epigenetic modulation model of mitochondrial DNA (mtDNA) is selected because mtDNA establishes a relative hypermethylation stage under oxidative stress, which impairs the mitochondrion-based therapeutic effect during cancer therapy. Herein, we design a new biocompatible hydrogen-bonded organic framework (HOF) for a HOF-based mitochondrion-targeting bioorthogonal platform TPP@P@PHOF-2. PHOF-2 can activate a prodrug (pro-procainamide) in situ, which can specifically inhibit DNA methyltransferase 1 (DNMT1) activity and remodel the epigenetic modification of mtDNA, making it more susceptible to ROS damage. In addition, PHOF-2 can also catalyze artemisinin to produce large amounts of ROS, effectively damaging mtDNA and achieving better chemodynamic therapy demonstrated by both in vitro and in vivo studies. This work provides new insights into developing advanced bioorthogonal therapy and expands the applications of HOF and bioorthogonal catalysis.

Effectiveness and safety of a novel modified homemade snare in retrograde percutaneous coronary intervention for chronic total occlusion lesions: a retrospective cohort study.

Background: The use of a commercial snare for retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is time-consuming and expensive. This study aimed to evaluate the benefits and complications of a novel modified homemade snare (MHS) for retrograde CTO-PCI. Methods: This retrospective cohort study included patients with CTO who underwent retrograde PCI with guidewire snaring between January 2017 and June 2022 at Beijing Anzhen Hospital. The patients were divided into the MHS and gooseneck snare (GS) groups according to the devices used for externalization. Clinical, procedural, and angiographic data were collected. Results: Ninety patients (46 with MHS and 44 with GS) were included. There was no significant difference in the location of the CTO vessel between the MHS and GS groups, and the target CTO vessel was mainly located in the right coronary artery (RCA) in both groups (73.9% and 68.2% respectively). There were no significant differences in the J-CTO (Multicenter CTO Registry in Japan) and PROGRESS-CTO (Prospective Global Registry for the Study of Chronic Total Occlusion Intervention) scores between the two groups. More patients in the MHS group had lesions with ambiguous proximal caps compared with the GS group (54.3% vs. 31.8%, P=0.04). Retrograde wire crossing technique was used more in the GS group (54.5% vs. 41.3%, P=0.04), while reverse-controlled antegrade and retrograde subintimal tracking (CART) technique was used more in the MHS group (58.7% vs. 45.5%, P=0.037). The mean guidewire capture time was shorter in the MHS group than in the GS group (2.7±0.6 vs. 3.4±0.7 min, P<0.001). One case of delayed pericardial tamponade was observed in the MHS group. No other complications occurred. Conclusions: MHS appears to facilitate externalization in retrograde PCI for complex CTO lesions.

Serine protease Rv2569c facilitates transmission of Mycobacterium tuberculosis via disrupting the epithelial barrier by cleaving E-cadherin.

Epithelial cells function as the primary line of defense against invading pathogens. However, bacterial pathogens possess the ability to compromise this barrier and facilitate the transmigration of bacteria. Nonetheless, the specific molecular mechanism employed by Mycobacterium tuberculosis (M.tb) in this process is not fully understood. Here, we investigated the role of Rv2569c in M.tb translocation by assessing its ability to cleave E-cadherin, a crucial component of cell-cell adhesion junctions that are disrupted during bacterial invasion. By utilizing recombinant Rv2569c expressed in Escherichia coli and subsequently purified through affinity chromatography, we demonstrated that Rv2569c exhibited cell wall-associated serine protease activity. Furthermore, Rv2569c was capable of degrading a range of protein substrates, including casein, fibrinogen, fibronectin, and E-cadherin. We also determined that the optimal conditions for the protease activity of Rv2569c occurred at a temperature of 37°C and a pH of 9.0, in the presence of MgCl2. To investigate the function of Rv2569c in M.tb, a deletion mutant of Rv2569c and its complemented strains were generated and used to infect A549 cells and mice. The results of the A549-cell infection experiments revealed that Rv2569c had the ability to cleave E-cadherin and facilitate the transmigration of M.tb through polarized A549 epithelial cell layers. Furthermore, in vivo infection assays demonstrated that Rv2569c could disrupt E-cadherin, enhance the colonization of M.tb, and induce pathological damage in the lungs of C57BL/6 mice. Collectively, these results strongly suggest that M.tb employs the serine protease Rv2569c to disrupt epithelial defenses and facilitate its systemic dissemination by crossing the epithelial barrier.

Multi-component Copolymerized Donors enable Frozen Nano-morphology and Superior Ductility for Efficient Binary Organic Solar Cells.

Multi-component copolymerized donors (MCDs) have gained significant interest and have been rapidly developed in flexible organic solar cells (f-OSCs) in recent years. However, ensuring the power conversion efficiency (PCE) of f-OSCs while retaining ideal mechanical properties remains an enormous challenge. The fracture strain (FS) value of typical high-efficiency blend films is generally less than 8 %, which is far from the application standards of wearable photovoltaic devices. Therefore, we developed a series of novel MCDs after meticulous molecular design. Among them, the consistent MCD backbone and end-capped functional group formed a highly conjugated molecular plane, and the solubilization and mechanical properties were effectively optimized by modifying the proportion of solubilized alkyl chains. Consequently, due to the formation of entangled structures with a frozen blend film morphology considerably improved the high ductility of the active layer, P10.8/P20.2-TCl exhibited efficient PCE in rigid (18.53 %) and flexible (17.03 %) OSCs, along with excellent FS values (16.59 %) in pristine films, meanwhile, the outstanding FS values of 25.18 % and 12.3 % were achieved by P10.6/P20.4-TCl -based pristine and blend films, respectively, which were one of the highest records achieved by end-capped MCD-based binary OSCs, demonstrating promising application to synchronize the realization of high-efficiency and mechanically ductile flexible OSCs.

Corrigendum: Expression profiling of ALOG family genes during inflorescence development and abiotic stress responses in rice (Oryza sativa L.).

[This corrects the article DOI: 10.3389/fgene.2024.1381690.].

Metabolomics reveals ascorbic acid inhibits ferroptosis in hepatocytes and boosts the effectiveness of anti-PD1 immunotherapy in hepatocellular carcinoma.

BACKGROUND: Immunotherapy combined with molecular targeted therapy is increasingly popular in patients with advanced hepatocellular carcinoma (HCC). However, immune-related adverse events(irAEs) brought on by immunotherapy increase the likelihood of side effects, thus it is important to look into ways to address this issue. METHODS: Different metabolite patterns were established by analyzing metabolomics data in liver tissue samples from 10 patients(divided into severe and mild liver injury) before and after immuno-targeted therapy. After establishing a subcutaneous tumor model of HCC, the mice were divided into PBS group, ascorbic acid(AA) group, and anti-PD1 + tyrosine kinase inhibitor (TKI) group, anti-PD1 + TKI + AA group. Liver tissue were stained with hematoxylin-eosin staining(HE) and the content of aspartate transaminase (AST) and alanine transaminase(ALT) in blood were determined. The mechanism was confirmed by western blotting, mass cytometry, and other techniques. RESULTS: Through metabolomics analysis, AA was significantly reduced in the sample of patients with severe liver injury caused by immuno-targeted therapy compared to patients with mild liver injury. The addition of AA in vivo experiments demonstrated a reduction in liver injury in mice. In the liver tissues of the anti-PD1 + TKI + AA group, the protein expressions of SLC7A11,GPX4 and the level of glutathione(GSH) were found to be higher compared to the anti-PD1 + TKI group. Mass cytometry analysis revealed a significant increase in the CD11b+CD44+ PD-L1+ cell population in the AA group when compared to the PBS group. CONCLUSIONS: AA could reduce liver injury by preventing hepatocyte SLC7A11/GPX4 ferroptosis and improve the immunotherapy effect of anti-PD1 by boosting CD11b+CD44+PD-L1+cell population in HCC.

Simultaneous Enhancement of the Thermostability and Catalytic Activity of D-Allulose 3-Epimerase from Clostridium bolteae ATTC BAA-613 Based on the "Back to Consensus Mutations" Hypothesis.

D-Allulose is a high value rare sugar with multiple physiological functions and commercial potential that can be enzymatically synthesized from D-fructose by D-allulose 3-epimerase (DAEase). Poor catalytic activity and thermostability of DAEase prevent the industrial production of D-allulose. In this work, rational design was applied to a previously identified DAEase from Clostridium bolteae ATCC BAA-613 based on the "back to consensus mutations" hypothesis, and the catalytic activity of the Cb-I265 V variant was enhanced 2.5-fold. Furthermore, the Cb-I265 V/E268D double-site variant displayed 2.0-fold higher specific catalytic activity and 1.4-fold higher thermostability than the wild-type enzyme. Molecular docking and kinetic simulation results indicated increased hydrogen bonds between the active pocket and substrate, possibly contributing to the improved thermal stability and catalytic activity of the double-site mutant. The findings outlined a feasible approach for the rational design of multiple preset functions of target enzymes simultaneously.

High expression of SULF1 is associated with adverse prognosis in breast cancer brain metastasis.

BACKGROUND: Breast cancer is the most common cancer in women, and in advanced stages, it often metastasizes to the brain. However, research on the biological mechanisms of breast cancer brain metastasis and potential therapeutic targets are limited. METHODS: Differential gene expression analysis (DEGs) for the datasets GSE43837 and GSE125989 from the GEO database was performed using online analysis tools such as GEO2R and Sangerbox. Further investigation related to SULF1 was conducted using online databases such as Kaplan-Meier Plotter and cBioPortal. Thus, expression levels, variations, associations with HER2, biological processes, and pathways involving SULF1 could be analyzed using UALCAN, cBioPortal, GEPIA2, and LinkedOmics databases. Moreover, the sensitivity of SULF1 to existing drugs was explored using drug databases such as RNAactDrug and CADSP. RESULTS: High expression of SULF1 was associated with poor prognosis in advanced breast cancer brain metastasis and was positively correlated with the expression of HER2. In the metastatic breast cancer population, SULF1 ranked top among the 16 DEGs with the highest mutation rate, reaching 11%, primarily due to amplification. KEGG and GSEA analyses revealed that the genes co-expressed with SULF1 were positively enriched in the 'ECM-receptor interaction' gene set and negatively enriched in the 'Ribosome' gene set. Currently, docetaxel and vinorelbine can act as treatment options if the expression of SULF1 is high. CONCLUSIONS: This study, through bioinformatics analysis, unveiled SULF1 as a potential target for treating breast cancer brain metastasis (BM).

The ldp1 Mutation Affects the Expression of Auxin-Related Genes and Enhances SAM Size in Rice.

Panicle type is one of the important factors affecting rice (Oryza sativa L.) yield, and the identification of regulatory genes in panicle development can provide significant insights into the molecular network involved. This study identified a large and dense panicle 1 (ldp1) mutant produced from the Wuyunjing 7 (WYJ7) genotype, which displayed significant relative increases in panicle length, number of primary and secondary branches, number of grains per panicle, grain width, and grain yield per plant. Scanning electron microscopy results showed that the shoot apical meristem (SAM) of ldp1 was relatively larger at the bract stage (BM), with a significantly increased number of primary (PBM) and secondary branch (SBM) meristematic centers, indicating that the ldp1 mutation affects early stages in SAM development Comparative RNA-Seq analysis of meristem tissues from WYJ7 and ldp1 at the BM, PBM, and SBM developmental stages indicated that the number of differentially expressed genes (DEGs) were highest (1407) during the BM stage. Weighted gene coexpression network analysis (WGCNA) revealed that genes in one module (turquoise) are associated with the ldp1 phenotype and highly expressed during the BM stage, suggesting their roles in the identity transition and branch differentiation stages of rice inflorescences. Hub genes involved in auxin synthesis and transport pathways, such as OsAUX1, OsAUX4, and OsSAUR25, were identified. Moreover, GO and KEGG analysis of the DEGs in the turquoise module and the 1407 DEGs in the BM stage revealed that a majority of genes involved in tryptophan metabolism and auxin signaling pathway were differentially expressed between WYJ and ldp1. The genetic analysis indicated that the ldp1 phenotype is controlled by a recessive monogene (LDP1), which was mapped to a region between 16.9 and 18.1 Mb on chromosome seven. This study suggests that the ldp1 mutation may affect the expression of key genes in auxin synthesis and signal transduction, enhance the size of SAM, and thus affect panicle development. This study provides insights into the molecular regulatory network underlying rice panicle morphogenesis and lays an important foundation for further understanding the function and molecular mechanism of LDP1 during panicle development.

Energy band modulation of Li2O-rGO core-shell as cathode sacrificial additive enables capacity enhancement of hard carbon anode in Li-ion batteries.

Lithium oxides (Li2O) possess a considerable theoretical capacity, rendering them highly promising as cathodic pre-lithiation additives. However, its decomposition voltage exceeds the charging cut-off voltage of most cathode materials, hindering its direct use as a cathode sacrificial additive. Herein, we design a facile and safe method to reduce the decomposition energy of Li2O at room temperature to offset the irreversible capacity loss by using a core-shell structured Li2O-reduced graphene oxide (rGO)-polyethylene glycol (PEG) composite (denoted as Li2O-rGO-PEG). The graphene oxide (GO) was heat-treated to remove oxygen functional groups to synthesize rGO, and then reacted with Li2O to form a Li2O-rGO composite. According to the DFT calculations, the density of states at the Fermi level of Li2O-rGO becomes continuous and features a metallic nature, which significantly improves the electrical conductivity of Li2O and facilitates electron conduction that modify the delithiation potential of Li2O. PEG was used to enhance the cohesive force between rGO and Li2O and to protect Li2O from atmospheric contamination. Moreover, in order to demonstrate the excellent pre-lithiation ability of Li2O-rGO-PEG composite, hard carbon (HC) with low initial coulombic efficiency (ICE) was used as the anode. In the application of LFP (Li2O)/HC full cell, Li2O was decomposed to Li+ to effectively improve the initial charge capacity from 149.7 to 200 mAh/g and discharge capacity from 104.2 to 147.5 mAh/g, which are 33.6 % and 41.6 % higher than those of the pristine LFP/HC full cell, respectively. The cathode pre-lithiation method proposed in this work is simple and environmentally friendly. The successful utilization of Li2O as a pre-lithiation additive effectively addressed the issue of low initial coulombic efficiency of the HC, indicating excellent prospects for practical applications.

Proteomic study of vitreous in proliferative diabetic retinopathy patients after treatment with aflibercept: a quantitative analysis based on 4D label-free technique.

AIM: To identify different metabolites, proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy (PDR) and resistance to anti-vascular endothelial growth factor (VEGF) drugs, and to provide biomarkers for the diagnosis and treatment of PDR. METHODS: Vitreous specimens from patients with diabetic retinopathy were collected and analyzed by Liquid Chromatography-Mass Spectrometry (LC-MS/MS) analyses based on 4D label-free technology. Statistically differentially expressed proteins (DEPs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway representation and protein interactions were analyzed. RESULTS: A total of 12 samples were analyzed. The proteomics results showed that a total of 58 proteins were identified as DEPs, of which 47 proteins were up-regulated and 11 proteins were down-regulated. We found that C1q and tumor necrosis factor related protein 5 (C1QTNF5), Clusterin (CLU), tissue inhibitor of metal protease 1 (TIMP1) and signal regulatory protein alpha (SIRPα) can all be specifically regulated after aflibercept treatment. GO functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by PDR. In addition, protein-protein interaction (PPI) network evaluation revealed that TIMP1 plays a central role in neural regulation. In addition, CD47/SIRPα may become a key target to resolve anti-VEGF drug resistance in PDR. CONCLUSION: Proteomic analysis is an approach of choice to explore the molecular mechanisms of PDR. Our data show that multiple proteins are differentially changed in PDR patients after intravitreal injection of aflibercept, among which C1QTNF5, CLU, TIMP1 and SIRPα may become targets for future treatment of PDR and resolution of anti-VEGF resistance.

A Sequentially Activated Probe for Imaging of Superoxide Anion and Peroxynitrite in PC12 Cells under Oxidative Stress.

Superoxide anion (O2·-) and peroxynitrite (ONOO-), two important oxidants under oxidative stress, coexist in complex cell and organism systems, playing crucial roles in various physiological and pathological processes, particularly in neurodegenerative diseases. Despite the absence of robust molecular tools capable of simultaneously visualizing O2·- and ONOO- in biosystems, the relationship between these two species remains understudied. Herein, we present sequentially activated fluorescent probe, DHX-SP, which exhibits exceptional selectivity and sensitivity toward O2·- and ONOO-. This probe enables precise imaging of these species in living PC12 cells under oxidative stress conditions using distinct fluorescence signal combinations. Furthermore, the probe DHX-SP has the ability to visualize changes in O2·- and ONOO- levels during ferroptosis of PC12 cells and in the Parkinson's disease model. These findings establish a connection between the crosstalk of the phosphorus group of O2·- and ONOO- in PC12 cells under oxidative stress.