ZO-1 and IL-1RAP Phosphorylation: Potential Role in Mediated Brain-Gut Axis Dysregulation in Irritable Bowel Syndrome-like Stressed Mice.

Background and Objectives: Irritable Bowel Syndrome (IBS) is a common gastrointestinal disorder often exacerbated by stress, influencing the brain-gut axis (BGA). BGA dysregulation, disrupted intestinal barrier function, altered visceral sensitivity and immune imbalance defects underlying IBS pathogenesis have been emphasized in recent investigations. Phosphoproteomics reveals unique phosphorylation details resulting from environmental stress. Here, we employ phosphoproteomics to explore the molecular mechanisms underlying IBS-like symptoms, mainly focusing on the role of ZO-1 and IL-1RAP phosphorylation. Materials and Methods: Morris water maze (MWM) was used to evaluate memory function for single prolonged stress (SPS). To assess visceral hypersensitivity of IBS-like symptoms, use the Abdominal withdrawal reflex (AWR). Colonic bead expulsion and defecation were used to determine fecal characteristics of the IBS-like symptoms. Then, we applied a phosphoproteomic approach to BGA research to discover the molecular mechanisms underlying the process of visceral hypersensitivity in IBS-like mice following SPS. ZO-1, p-S179-ZO1, IL-1RAP, p-S566-IL-1RAP and GFAP levels in BGA were measured by western blotting, immunofluorescence staining, and enzyme-linked immunosorbent assay to validate phosphorylation quantification. Fluorescein isothiocyanate-dextran 4000 and electron-microscopy were performed to observe the structure and function of the intestinal epithelial barrier. Results: The SPS group showed changes in learning and memory ability. SPS exposure affects visceral hypersensitivity, increased fecal water content, and significant diarrheal symptoms. Phosphoproteomic analysis displayed that p-S179-ZO1 and p-S566-IL-1RAP were significantly differentially expressed following SPS. In addition, p-S179-ZO1 was reduced in mice's DRG, colon, small intestine, spinal and hippocampus and intestinal epithelial permeability was increased. GFAP, IL-1ß and p-S566-IL-1RAP were also increased at the same levels in the BGA. And IL-1ß showed no significant difference was observed in serum. Our findings reveal substantial alterations in ZO-1 and IL-1RAP phosphorylation, correlating with increased epithelial permeability and immune imbalance. Conclusions: Overall, decreased p-S179-ZO1 and increased p-S566-IL-1RAP on the BGA result in changes to tight junction structure, compromising the structure and function of the intestinal epithelial barrier and exacerbating immune imbalance in IBS-like stressed mice.

Carvedilol to prevent decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by liver stiffness: study protocol for a randomied, double-blind, placebo-controlled, multicentre trial in China.

INTRODUCTION: Patients with clinically significant portal hypertension (CSPH) are recommended to be treated with non-selective beta-blockers (ie, carvedilol) to prevent the first hepatic decompensation event by the renewing Baveno VII consensus. CSPH is defined by hepatic venous pressure gradient (HVPG)≥10 mm Hg; however, the HVPG measurement is not widely adopted due to its invasiveness. Liver stiffness (LS)≥25 kPa can be used as a surrogate of HVPG≥10 mm Hg to rule in CSPH with 90% of the positive predicting value in majority aetiologies of patients. A compelling argument is existing for using LS≥25 kPa to diagnose CSPH and then to initiate carvedilol in patients with compensated cirrhosis, and about 5%-6% of patients under this diagnosis criteria may not be benefited from carvedilol and are at risk of lower heart rate and mean arterial pressure. Randomised controlled trial on the use of carvedilol to prevent liver decompensation in CSPH diagnosed by LS remains to elucidate. Therefore, we aimed to investigate if compensated cirrhosis patients with LS≥25 kPa may benefit from carvedilol therapy. METHODS AND ANALYSIS: This study is a randomised, double-blind, placebo-controlled, multicentre trial. We will randomly assign 446 adult compensated cirrhosis patients with LS≥25 kPa and without any previous decompensated event and without high-risk gastro-oesophageal varices. Patients are randomly divided into two groups, with 223 subjects in group A and 223 subjects in group B. Group A is a carvedilol intervention group, while group B is a placebo group. All patients in both groups will receive aetiology therapies and are followed up at an interval of 6 months. The 3-year incidences of decompensated events of cirrhosis-related and liver-related death are the primary outcome. The secondary outcomes include development of each complication of portal hypertension individually (ascites, variceal bleeding or overt hepatic encephalopathy), development of spontaneous bacterial peritonitis and other bacterial infections, development of new varices, growth of small varices to large varices, delta changes in LS and spleen stiffness, change in hepatic dysfunction assessed by Child-Pugh and model for end-stage liver disease score, change in platelet count, development of hepatocellular carcinoma, development of portal vein thrombosis and adverse events with a 3-year follow-up. A predefined interim analysis will be performed to ensure that the calculation is reasonable. ETHICS AND DISSEMINATION: The study protocol has been approved by the ethics committees of the Sixth People's Hospital of Shenyang (2023-05-003-01) and independent ethics committee for clinical research of Zhongda Hospital, affiliated to Southeast University (2023ZDSYLL433-P01). The results from this trial will be submitted for publication in peer-reviewed journals and will be presented at international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300073864.

The Role and Therapeutic Potential of Pyroptosis in Colorectal Cancer: A Review.

Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. The unlimited proliferation of tumor cells is one of the key features resulting in the malignant development and progression of CRC. Consequently, understanding the potential proliferation and growth molecular mechanisms and developing effective therapeutic strategies have become key in CRC treatment. Pyroptosis is an emerging type of regulated cell death (RCD) that has a significant role in cells proliferation and growth. For the last few years, numerous studies have indicated a close correlation between pyroptosis and the occurrence, progression, and treatment of many malignancies, including CRC. The development of effective therapeutic strategies to inhibit tumor growth and proliferation has become a key area in CRC treatment. Thus, this review mainly summarized the different pyroptosis pathways and mechanisms, the anti-tumor (tumor suppressor) and protective roles of pyroptosis in CRC, and the clinical and prognostic value of pyroptosis in CRC, which may contribute to exploring new therapeutic strategies for CRC.

Deciphering the interplay between wastewater compositions and oxytetracycline in recovered struvite: Unveiling mechanisms and introducing control strategies.

Struvite recovery from wastewater offers a sustainable phosphorus and nitrogen source, yet it harbors the challenge of variable antibiotic residues, notably oxytetracycline (OTC), increasing the ecological risk during subsequent use. Despite the need, mechanisms behind these residues and regulatory solutions remain obscure. We characterized OTC in recovered struvite and showed that increased dissolved organic matter (DOM) enhanced OTC accumulation, while PO43- suppressed it. NH4+ modulated OTC levels through the saturation index (SI), with a rise in SI significantly reducing OTC content. Additionally, excess Mg2+ formed complexes with OTC and DOM (humic acid, HA), leading to increased residue levels. Complexation was stronger at higher pH, whereas electrostatic interactions dominated at lower pH. The primary binding sites for antibiotics and DOM were Mg-OH and P-OH groups in struvite. OTC's dimethylamino, amide, and phenolic diketone groups primarily bound to struvite and DOM, with the carboxyl group of DOM serving as the main binding site. Mg2+ complexation was the primary pathway for OTC transportation, whereas electrostatic attraction of PO43- dominated during growth. Controlling magnesium (Mg) dosage and adjusting pH were effective for reducing OTC in recovered products. Our findings provided insights into the intricate interactions between struvite and antibiotics, laying the groundwork for further minimizing antibiotic residues in recovered phosphorus products.

Phosphorus recovery and tetracycline Mitigation: The role of Bacillus cereus LB-9 in struvite biomineralization from wastewater.

Struvite biomineralization is an ecologically sound technology, adept at the efficient recovery and recycling of phosphorus from wastewater. However, the biomineralization process is often perturbed by the presence of antibiotics, notably tetracycline (TC), the impact of which on the biomineralization system has not been elucidated. This study examines the efficacy of Bacillus cereus LB-9 in struvite biomineralization, focusing on the precipitates' composition, morphology, and TC content. LB-9 facilitate an alkaline environment that effectively recovering nitrogen and phosphorus. These findings indicate that TC retards the initial formation of struvite and the concurrent recovery of nitrogen and phosphorus. However, at concentrations below 10 mg/L TC concentrations, TC enhanced struvite production (0.38g) by stimulating LB-9's growth and metabolic activity. Conversely, at a concentration of 10 mg/L TC, the strain's activity was markedly suppressed within the initial four days. This data suggests that TC promotes the strain's proliferation and metabolism, potentially through cellular secretions, thereby augmenting phosphorus recovery from wastewater. Notably, the recovered struvite doesn't contain TC, aligning with regulatory standards for agricultural application. In summary, LB-9-mediated struvite recovery is an effective strategy for producing phosphorus-enriched fertilizers and mitigating TC contamination, offering significant implications for wastewater treatment and industrial process development, particularly in the context of prevalent TC in wastewater.

Analysis of the Fungal Community Composition in Endemic Orchids with Terrestrial Habitat in Subtropical Regions.

Habenaria and Liparis are well-known orchid genera that grow in terrestrial habitats in the tropics, subtropics or temperate zones. Three species have been found in subtropical regions of China, inhabiting terrestrial to epiphytic habitats. This study focuses on three species, H. dentata (distributed in Asia), H. yachangensis, and L. gigantea. For H. yachangensis and L. gigantea, there is no information about the mycorrhizal community in these species. This study aims to conduct the fungal community screening of Chinese ground orchids from subtropical regions. We performed a comparative analysis of the fungal community among H. dentata, H. yachangensis, and L. gigantea, determining their ITS regions using NGS paired-end sequences. The results clarified the diversity and the predominance of fungal genera. Ascomycota was abundant compared to Basidiomycota or other fungi groups in all communities, with a high dominance in all populations, especially for L. gigantea. At different root spatial locations, the fungal community diversity and richness were higher in the soil than in the rhizosphere or inner root. However, the results suggest that L. gigantea has a different fungal community compared to Habenaria species. In this order, the subtropical terrestrial orchids have a different fungal network compared to the northern terrestrial orchids. Also, there is a high probability of co-existence and co-evolution of endophytic fungi in these terrestrial orchids, indicating the potential role of host plants in selecting an endophytic fungal community. Furthermore, our results highlight the need to elucidate the microbe interactions of these unique orchids for long-term purposes, such as isolating indigenous fungi for suitable inoculants for further orchid propagation, restoration, and conservation.

Palladium-Catalyzed Carbonylative Sonogashira Coupling of Aryl Thianthrenium Salts with Arylalkynes.

Alkynones are valuable compounds with applications in various areas. In this work, we developed an efficient carbonylation procedure for the carbonylative cross-coupling of aryl thianthrenium salts with aromatic alkynes. Various useful alkynones were produced in moderate to excellent yields under mild conditions. Notably, among the various tolerated functional groups, the bromide group can be maintained, which is ready for further coupling reactions.

Variation of Chemical Microenvironment of Pores in Hydrazone-Linked Covalent Organic Frameworks for Photosynthesis of H2O2.

Photocatalytic synthesis of H2O2 is an advantageous and ecologically sustainable alternative to the conventional anthraquinone process. However, achieving high conversion efficiency without sacrificial agents remains a challenge. In this study, two covalent organic frameworks (COF-O and COF-C) were prepared with identical skeletal structures but with their pore walls anchored to different alkyl chains. They were used to investigate the effect of the chemical microenvironment of pores on photocatalytic H2O2 production. Experimental results reveal a change of hydrophilicity in COF-O, leading to suppressed charge recombination, diminished charge transfer resistance, and accelerated interfacial electron transfer. An apparent quantum yield as high as 10.3% (λ = 420 nm) can be achieved with H2O and O2 through oxygen reduction reaction. This is among the highest ever reported for polymer photocatalysts. This study may provide a novel avenue for optimizing photocatalytic activity and selectivity in H2O2 generation.

Defect-Rich Metastable MoS2 Promotes Macrophage Reprogramming in Breast Cancer: A Clinical Perspective.

Tumor-associated macrophages (TAMs) play a crucial function in solid tumor antigen clearance and immune suppression. Notably, 2D transitional metal dichalcogenides (i.e., molybdenum disulfide (MoS2) nanozymes) with enzyme-like activity are demonstrated in animal models for cancer immunotherapy. However, in situ engineering of TAMs polarization through sufficient accumulation of free radical reactive oxygen species for immunotherapy in clinical samples remains a significant challenge. In this study, defect-rich metastable MoS2 nanozymes, i.e., 1T2H-MoS2, are designed via reduction and phase transformation in molten sodium as a guided treatment for human breast cancer. The as-prepared 1T2H-MoS2 exhibited enhanced peroxidase-like activity (≈12-fold enhancement) than that of commercial MoS2, which is attributed to the charge redistribution and electronic state induced by the abundance of S vacancies. The 1T2H-MoS2 nanozyme can function as an extracellular hydroxyl radical generator, efficiently repolarizing TAMs into the M1-like phenotype and directly killing cancer cells. Moreover, the clinical feasibility of 1T2H-MoS2 is demonstrated via ex vivo therapeutic responses in human breast cancer samples. The apoptosis rate of cancer cells is 3.4 times greater than that of cells treated with chemotherapeutic drugs (i.e., doxorubicin).

The regulatory mechanism of rapid lignification for timely anther dehiscence.

Anther dehiscence is a crucial event in plant reproduction, tightly regulated and dependent on the lignification of the anther endothecium. In this study, we investigated the rapid lignification process that ensures timely anther dehiscence in Arabidopsis. Our findings reveal that endothecium lignification can be divided into two distinct phases. During Phase I, lignin precursors are synthesized without polymerization, while Phase II involves simultaneous synthesis of lignin precursors and polymerization. The transcription factors MYB26, NST1/2, and ARF17 specifically regulate the pathway responsible for the synthesis and polymerization of lignin monomers in Phase II. MYB26-NST1/2 is the key regulatory pathway responsible for endothecium lignification, while ARF17 facilitates this process by interacting with MYB26. Interestingly, our results demonstrate that the lignification of the endothecium, which occurs within approximately 26 h, is much faster than that of the vascular tissue. These findings provide valuable insights into the regulation mechanism of rapid lignification in the endothecium, which enables timely anther dehiscence and successful pollen release during plant reproduction.

Context-Enhanced Network with Spatial-Aware Graph for Smartphone Screen Defect Detection.

Interactive devices such as touch screens have gained widespread usage in daily life; this has directed the attention of researchers to the quality of screen glass. Consequently, defect detection in screen glass is essential for improving the quality of smartphone screens. In recent years, defect detection methods based on deep learning have played a crucial role in improving detection accuracy and robustness. However, challenges have arisen in achieving high-performance detection due to the small size, irregular shapes and low contrast of defects. To address these challenges, this paper proposes CE-SGNet, a Context-Enhanced Network with a Spatial-aware Graph, for smartphone screen defect detection. It consists of two novel components: the Adaptive Receptive Field Attention Module (ARFAM) and the Spatial-aware Graph Reasoning Module (SGRM). The ARFAM enhances defect features by adaptively extracting contextual information to capture the most relevant contextual region of defect features. The SGRM constructs a region-to-region graph and encodes region features with spatial relationships. The connections among defect regions are enhanced during the propagation process through a graph attention network. By enriching the feature representations of defect regions, the CE-SGNet can accurately identify and locate defects of various shapes and scales. Experimental results demonstrate that the CE-SGNet achieves outstanding performance on two public datasets.

Synthesis of Multisubstituted 2,3-Allenamides via Palladium-Catalyzed Carbonylation of Propargylic Esters.

2,3-Allenamides are an important class of unsaturated group-substituted carbonyl compounds. A palladium-catalyzed aminocarbonylation of propargyl acetates with amines for the synthesized tri-/tetrasubstituted 2,3-allenamides has been developed. A broad range of tri-/tetrasubstituted 2,3-allenamides have been prepared from propargyl acetates in good to excellent yields. The reaction featured mild reaction conditions and good functional group tolerance. The applicability of this methodology was further highlighted by the late-stage modification of several natural products and pharmaceuticals.

Manipulating the Spin State of Spinel Octahedral Sites via a π-π Type Orbital Coupling to Boost Water Oxidation.

Spin state is often regarded as the crucial valve to release the reactivity of energy-related catalysts, yet it is also challenging to precisely manipulate, especially for the active center ions occupied at the specific geometric sites. Herein, a π-π type orbital coupling of 3d (Co)-2p (O)-4f (Ce) was employed to regulate the spin state of octahedral cobalt sites (CoOh) in the composite of Co3O4/CeO2. More specifically, the equivalent high-spin ratio of CoOh can reach to 54.7% via tuning the CeO2 content, thereby triggering the average eg filling (1.094) close to the theoretical optimum value. The corresponding catalyst exhibits a superior water oxidation performance with an overpotential of 251 mV at 10 mA cm-2, rivaling most cobalt-based oxides state-of-the-art. The π-π type coupling corroborated by the matched energy levels between Ce t1u/t2u-O and CoOh t2g-O π type bond in the calculated crystal orbital Hamilton population and partial density of states profiles, stimulates a π-donation between O 2p and π-symmetric Ce 4fyz2 orbital, consequently facilitating the electrons hopping from t2g to eg orbital of CoOh. This work offers an in-depth insight into understanding the 4f and 3d orbital coupling for spin state optimization in composite oxides.

The development of catalysts and auxiliaries for the synthesis of covalent organic frameworks.

Covalent organic frameworks (COFs) have recently seen significant advancements. Large quantities of structurally & functionally oriented COFs with a wide range of applications, such as gas adsorption, catalysis, separation, and drug delivery, have been explored. Recent achievements in this field are primarily focused on advancing synthetic methodologies, with catalysts playing a crucial role in achieving highly crystalline COF materials, particularly those featuring novel linkages and chemistry. A series of reviews have already been published over the last decade, covering the fundamentals, synthesis, and applications of COFs. However, despite the pivotal role that catalysts and auxiliaries play in forming COF materials and adjusting their properties (e.g., crystallinity, porosity, stability, and morphology), limited attention has been devoted to these essential components. In this Critical Review, we mainly focus on the state-of-the-art progress of catalysts and auxiliaries applied to the synthesis of COFs. The catalysts include four categories: acid catalysts, base catalysts, transition-metal catalysts, and other catalysts. The auxiliaries, such as modulators, oxygen, and surfactants, are discussed as well. This is then followed by the description of several specific applications derived from the utilization of catalysts and auxiliaries. Lastly, a perspective on the major challenges and opportunities associated with catalysts and auxiliaries is provided.

The proliferation/migration ability mediated by CD151/PI3K/AKT pathway determines the therapeutic effect of hUC-MSCs transplantation on rheumatoid arthritis.

OBJECTIVE: To elucidate the underlying mechanism by which the proliferation and migration abilities of human umbilical cord mesenchymal stem cells (hUC-MSCs) determine their therapeutic efficacy in rheumatoid arthritis treatment. METHODS: The DBA/1J mice were utilized to establish a collagen-induced RA (CIA) mouse model and to validate the therapeutic efficacy of hUC-MSCs transfected with CD151 siRNA. RNA-seq, QT-PCR and western blotting were utilized to evaluate the mRNA and protein levels of the PI3K/AKT pathway, respectively. RESULTS: IFN-γ significantly enhanced the proliferation and migration abilities of hUC-MSCs, up-regulating the expression of CD151, a gene related to cell proliferation and migration. Effective inhibition of this effect was achieved through CD151 siRNA treatment. However, IFN-γ did not affect hUC-MSCs differentiation or changes in cell surface markers. Additionally, transplantation of CD151-interfered hUC-MSCs (siRNA-CD151-hUC-MSCs) resulted in decreased colonization in the toes of CIA mice and worse therapeutic effects compared to empty vector treatment (siRNA-NC-hUC-MSCs). CONCLUSION: IFN-γ facilitates the proliferation and migration of hUC-MSCs through the CD151/PI3K/AKT pathway. The therapeutic efficacy of siRNA-CD151-hUC-MSCs was found to be inferior to that of siRNA-NC-hUC-MSCs.

Photoactivated Gas-Generating Nanocontrast Agents for Long-Term Ultrasonic Imaging-Guided Combined Therapy of Tumors.

To date, long-term and continuous ultrasonic imaging for guiding the puncture biopsy remains a challenge. In order to address this issue, a multimodality imaging and therapeutic method was developed in the present study to facilitate long-term ultrasonic and fluorescence imaging-guided precision diagnosis and combined therapy of tumors. In this regard, certain types of photoactivated gas-generating nanocontrast agents (PGNAs), capable of exhibiting both ultrasonic and fluorescence imaging ability along with photothermal and sonodynamic function, were designed and fabricated. The advantages of these fabricated PGNAs were then utilized against tumors in vivo, and high therapeutic efficacy was achieved through long-term ultrasonic imaging-guided treatment. In particular, the as-prepared multifunctional PGNAs were applied successfully for the fluorescence-based determination of patient tumor samples collected through puncture biopsy in clinics, and superior performance was observed compared to the clinically used SonoVue contrast agents that are incapable of specifically distinguishing the tumor in ex vivo tissues.

Whole-Cell Bioconversion Systems for Efficient Synthesis of Monolignols from L-Tyrosine in Escherichia coli.

Monolignols and their derivatives exhibit various pharmaceutical and physiological characteristics, such as antioxidant and anti-inflammatory properties. However, they remain difficult to synthesize. In this study, we engineered several whole-cell bioconversion systems with carboxylate reductase (CAR)-mediated pathways for efficient synthesis of p-coumaryl, caffeyl, and coniferyl alcohols from l-tyrosine in Escherichia coli BL21 (DE3). By overexpressing the l-tyrosine ammonia lyase from Flavobacterium johnsoniae (FjTAL), carboxylate reductase from Segniliparus rugosus (SruCAR), alcohol dehydrogenase YqhD and hydroxylase HpaBC from E. coli, and caffeate 3-O-methyltransferase (COMT) from Arabidopsis thaliana, three enzyme cascades FjTAL-SruCAR-YqhD, FjTAL-SruCAR-YqhD-HpaBC, and FjTAL-SruCAR-YqhD-HpaBC-COMT were constructed to produce 1028.5 mg/L p-coumaryl alcohol, 1015.3 mg/L caffeyl alcohol, and 411.4 mg/L coniferyl alcohol from 1500, 1500, and 1000 mg/L l-tyrosine, with productivities of 257.1, 203.1, and 82.3 mg/L/h, respectively. This work provides an efficient strategy for the biosynthesis of p-coumaryl, caffeyl, and coniferyl alcohols from l-tyrosine.

WTAP/YTHDF1-mediated m6A modification amplifies IFN-γ-induced immunosuppressive properties of human MSCs.

INTRODUCTION: The immunosuppressive capacity of mesenchymal stem cells (MSCs) is dependent on the "license" of several pro-inflammatory factors to express immunosuppressive molecular profiles, which determines the therapeutic efficacy of MSCs in immune-mediated inflammatory diseases. Of those, interferon-γ (IFN-γ) is a key inducer for the expression of immunosuppressive molecular profiles; however, the mechanism underlying this effect is unknown. OBJECTIVES: To elucidate the regulation mechanism and biological functions of N6-methyladenosine (m6A) modification in the immunosuppressive functions by the IFN-γ-licensing MSCs. METHODS: Epitranscriptomic microarray analysis and MeRIP-qPCR assay were performed to identify the regulatory effect of WTAP in the IFN-γ-licensing MSCs. RIP-qPCR, western blot, qRT-PCR and RNA stability assays were used to determine the regulation of WTAP/m6A/YTHDF1 signaling axis in the expression of immunosuppressive molecules. Further, functional capacity of T cells was tested using flow cytometry, and both DSS-induced colitis mice and CIA mice were constructed to clarify the effect of WTAP and YTHDF1 in MSC-mediated immunosuppression. RESULTS: We identified that IFN-γ increased the m6A methylation levels of immunosuppressive molecules, while WTAP deficiency abolished the IFN-γ-induced promotion of m6A modification. IFN-γ activated ERK signaling, which induced WTAP phosphorylation. Additionally, the stabilization of WTAP post-transcriptionally increased the mRNA expression of immunosuppressive molecules (IDO1, PD-L1, ICAM1, and VCAM1) in an m6A-YTHDF1-dependent manner; this effect further impacted the immunosuppressive capacity of IFN-γ licensing MSCs on activated T cells. Notably, WTAP/YTHDF1 overexpression enhanced the therapeutic efficacy of IFN-γ licensing MSCs and restructures the ecology of inflammation in both colitis and arthritis models. CONCLUSION: Our results showed that m6A modification of IDO1, PD-L1, ICAM1, and VCAM1 mRNA mediated by WTAP-YTHDF1 is involved in the regulation of IFN-γ licensing MSCs immunosuppressive abilities, and shed a light to enhance the clinical therapeutic potential of IFN-γ-licensing MSCs.

Phosphorylated FOXQ1, a novel substrate of JNK1, inhibits sorafenib-induced ferroptosis by activating ETHE1 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a highly heterogeneous and malignant cancer with poor overall survival. The application of sorafenib is a major breakthrough in the treatment of HCC. In our study, FOXQ1 was significantly overexpressed in sorafenib-resistant HCC cells and suppressed sorafenib-induced ferroptosis. We found that phosphorylation of FOXQ1 at serine 248 is critical for the suppression of sorafenib-induced ferroptosis. Furthermore, as the upstream phosphorylation kinase of FOXQ1, JNK1, which is activated by sorafenib, can directly phosphorylate the serine 248 site of FOXQ1. Then, the phosphorylated FOXQ1 got a high affinity for the promoter of ETHE1 and activates its transcription. Further flow cytometry results showed that ETHE1 reduced intracellular lipid peroxidation and iron levels. Collectively, our study implicated the JNK1-FOXQ1-ETHE1 axis in HCC ferroptosis induced by sorafenib, providing mechanistic insight into sensitivity to sorafenib therapy of HCC.

Multiple uniform lithium-ion transport channels in Li6.4La3Zr1.4Ta0.6O12/Ce(OH)3 modified polypropylene composite separator for high-performance lithium metal batteries.

Lithium (Li) metal anodes (LMAs) are regarded as leading technology for advanced-generation batteries due to their high theoretical capacity and favorable redox potential. However, the practical integration of LMAs into high-energy rechargeable batteries is hindered by the challenge of Li dendrite growth. In this work, nanoparticles of Li6.4La3Zr1.4Ta0.6O12 (LLZTO) loaded with Ce(OH)3 (LLZTCO) were designed and synthesized by a hydrothermal method. A functional composite separator was crafted by coating one side of a polypropylene (PP) separator with a composite electrolyte comprised of polyvinylidene fluoride (PVDF) and LLZTCO. The synergistic interactions between PVDF and LLZTCO provide numerous rapid lithium-ion (Li+) channels, facilitating the efficient redistribution of disparate Li+ flux originating from the insulated PP separator. The composite separator demonstrated an ionic conductivity (σ) of 3.68 × 10-3 S cm-1, substantial Li+ transference number (t+) of 0.73, and a high electrochemical window of 4.8 V at 25℃. Furthermore, the Li/LLZTCO@PP/Li symmetric cells demonstrated stable cycling for over 2000 h without significant dendrite formation. The Li/LiFePO4 (LFP) cells assembled with LLZTCO@PP separators exhibited a capacity retention of 91.6 % after 400 cycles at 1C. This study offers a practical approach to fabricating composite separators with enhanced safety and superior electrochemical performance.