Chloride-Ion-Enriched Solid Electrolyte Interphase with Rapid Na+ Migration toward High-Performance Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) have emerged as potential alternatives to lithium-ion batteries (LIBs), particularly for large-scale applications. Alloy-type anode materials for sodium-ion batteries are esteemed as prospective candidate materials for sodium-ion anodes, owing to their elevated theoretical capacity, heightened utilization efficiency, and minimal production of insulating byproducts. However, the severe volume changes and sluggish ion diffusion kinetics can lead to irreversible particle fragmentation and reaggregation phenomena, ultimately resulting in electrode degradation. Additionally, repetitive volume changes can cause an unstable solid electrolyte interphase (SEI). This study presents the synthesis of chloride-ion-modulated bimetallic SnSb/C nanoparticle anode materials, highlighting the following advantages: (i) Designing a bimetallic SnSb alloy structure serves to buffer the structural stresses generated during sodium insertion/extraction processes, effectively mitigating particle fracture phenomena induced by electrode material expansion/contraction. (ii) Nanostructuring both alloy materials enables the full utilization of active materials and shortens diffusion pathways, thereby significantly enhancing the diffusion rate of sodium ions. (iii) Introducing a carbonaceous matrix serves to alleviate self-agglomeration phenomena of the material during charge/discharge cycles, enhancing the material's conductivity and structural stability. (iv) Utilizing chloride-ion interface modification to achieve a chloride-rich solid-electrolyte interphase (SEI) enhances battery performance.

Association between gestational hypnotic benzodiazepine receptor agonists exposure and adverse pregnancy outcomes: a systematic review and meta-analysis.

OBJECTIVE: Hypnotic benzodiazepine receptor agonists (HBRA) are frequently prescribed in pregnancy but little is known about their effects on pregnancy outcomes. Herein, we systematically reviewed the evidence on the effects of HBRA exposure during pregnancy and risk of preterm birth (PTB), small for gestational age (SGA), birth defects, and low birth weight (LBW). METHODS: We reviewed the databases of PubMed, CENTRAL, Embase, Scopus, and Web of Science from the earliest possible date to 17th May 2024 and included all studies examining adverse pregnancy outcomes with gestational exposure to HBRA. RESULTS: Nine studies were included. Meta-analysis showed that HBRA exposure led to a significant increase in the risk of PTB (OR: 1.28 95% CI: 1.05, 1.56 I2 = 73%), SGA (OR: 1.24 95% CI: 1.18, 1.30 I2 = 0%), and LBW (OR: 1.51 95% CI: 1.27, 1.78 I2 = 26%). We noted no significant association between HBRA exposure in pregnancy and subsequent birth defects (OR: 0.90 95% CI: 0.63, 1.28 I2 = 56%). Subgroup analysis based on exposure time, type of HBRA, method of assessment of exposure, control of psychiatric diagnosis, and psychotropic drugs altered the results of PTB and SGA but not for birth defects. CONCLUSION: HBRA exposure during pregnancy may lead to a small but significant increase in the risk of PTB, SGA, and LBW. HBRA is not associated with an increased risk of birth defects. There are several limitations of current evidence especially with regards to adjustment for psychiatric illness and co-mediations which need to be overcome by future studies.

Oxaliplatin activates P53/miR-34a/survivin axis in inhibiting the progression of gastric cancer cells.

INTRODUCTION: The purpose of this research was to determine how the P53/microRNA-34a (miR-34a)/survivin pathway contributes to oxaliplatin-induced (L-OHP) cell inhibition in gastric cancer. METHODS: The BGC-823 gastric cancer cells were selected, and we examined their viability following treatment with L-OHP at different concentrations and time periods. The expression levels of miR-34a, P53, and survivin in the cells were determined. RESULTS: In the 12- and 24-h groups, drug concentration of 15 µg/cm² (p < .005 in both) significantly lowered cell viability. In comparison to the control group, miR-34a mRNA expression, P53 mRNA expression, and protein expression were all significantly greater in the 24-h group (p = .0324, p = .0069, p = .0260, respectively), but survivin mRNA and protein expressions were significantly lower than those in the control group (p = .0338, p = .0032, respectively). There was a significant decrease in gastric cancer cells in the miR-34a overexpression group (p = .0020), a significant increase in P53 mRNA and protein expression compared to the control group (p = .0080, p = .0121, respectively), and a significant decrease in survivin mRNA and protein expression compared to the control group. (p = .0213, p = .0069, respectively). CONCLUSION: Oxaliplatin inhibits tumor growth, invasion, and metastasis by upregulating miR-34a, activating the expression of the upstream P53 gene, and driving the downregulation of survivin (P53/miR-34a/survivin axis) in BGC-823 gastric cancer cells.

Deciphering the mechanisms of the IL-6/CXCL1 and NOD-like receptor signaling pathways in otitis media with effusion in rodents.

BACKGROUND: Otitis media with effusion (OME) often leads to pediatric hearing loss and is influenced by innate and adaptive immune responses. Innate immunity serves as the non-specific first line of defense against OME. METHODS: We induced OME in rats using ovalbumin. We administered IL-6 monoclonal antibodies intranasally to inhibit IL-6, and we injected an NF-κB inhibitor intraperitoneally to explore the role of IL-6 in innate immunity and its interaction with the NOD-like receptor signaling pathway. We analyzed RNA-sequencing data with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways to assess signaling pathways involved in OME. We also utilized Western blot, quantitative real-time PCR, and immunohistochemistry on middle ear samples and used microscopy to identify immune cells in ear wash fluids. RESULTS: Our study suggests a pivotal role for IL-6 in the immune pathways of rats with OME via the regulation of CXCL1-mediated pathways. Increased levels of IL-6 and CXCL1 were observed in the middle ear tissues, and activation of the NLRP3 inflammasome in OME rats led to an immune response via NF-κB, thus promoting IL-6 and CXCL1 production, which was reduced by IL-6 antibody treatment. CONCLUSIONS: Our findings confirm that IL-6 and CXCL1 play significant roles in the innate immune response in OME in rodents, predominantly via the NOD-like receptor signaling pathway and NLRP3 inflammasome activation. This research sheds light on OME pathogenesis and its immune-related mechanisms.

Jasmonic acid plays an important role in mediating retrograde signaling under mitochondrial translational stress to balance plant growth and defense.

Proper mitochondrial function is crucial to plant growth and development. Inhibition of mitochondrial translation leads to mitochondrial proteotoxic stress, which triggers a protective transcriptional response that regulates nuclear gene expression, commonly referred to as the mitochondrial unfolded protein response (UPRmt). Although UPRmt has been extensively studied in yeast and mammals, very little is known about UPRmt in plants. Here, we show that mitochondrial translational stress inhibits plant growth and development by inducing jasmonic acid (JA) biosynthesis and signaling. The inhibitory effect of mitochondrial translational stress on plant growth was alleviated in JA signaling defective mutants coi1-2, myc2, and myc234. Genetic analysis indicates that Arabidopsis mitochondrial ribosomal protein L1 (MRPL1), a key factor in UPRmt, regulates plant growth in a CORONATINE-INSENSITIVE1 (COI1)-dependent manner. Moreover, under mitochondrial translational stress, MYC2 showed direct binding to G-boxes in the ETHYLENE RESPONSE FACTOR 109 (ERF109) promoter. The induction of ERF109 expression enhances hydrogen peroxide (H2O2) production, which acts as a feedback loop to inhibit root growth. In addition, mutation of MRPL1 increases JA accumulation, reduces plant growth, and enhances biotic stress resistance. Overall, our findings reveal that JA plays an important role in mediating retrograde signaling under mitochondrial translational stress to balance plant growth and defense.

Machine learning-based risk prediction of acute kidney disease and hospital mortality in older patients.

Introduction: Acute kidney injury (AKI) is a prevalent complication in older people, elevating the risks of acute kidney disease (AKD) and mortality. AKD reflects the adverse events developing after AKI. We aimed to develop and validate machine learning models for predicting the occurrence of AKD, AKI and mortality in older patients. Methods: We retrospectively reviewed the medical records of older patients (aged 65 years and above). To explore the trajectory of kidney dysfunction, patients were categorized into four groups: no kidney disease, AKI recovery, AKD without AKI, or AKD with AKI. We developed eight machine learning models to predict AKD, AKI, and mortality. The best-performing model was identified based on the area under the receiver operating characteristic curve (AUC) and interpreted using the Shapley additive explanations (SHAP) method. Results: A total of 22,005 patients were finally included in our study. Among them, 4,434 patients (20.15%) developed AKD, 4,000 (18.18%) occurred AKI, and 866 (3.94%) patients deceased. Light gradient boosting machine (LGBM) outperformed in predicting AKD, AKI, and mortality, and the final lite models with 15 features had AUC values of 0.760, 0.767, and 0.927, respectively. The SHAP method revealed that AKI stage, albumin, lactate dehydrogenase, aspirin and coronary heart disease were the top 5 predictors of AKD. An online prediction website for AKD and mortality was developed based on the final models. Discussion: The LGBM models provide a valuable tool for early prediction of AKD, AKI, and mortality in older patients, facilitating timely interventions. This study highlights the potential of machine learning in improving older adult care, with the developed online tool offering practical utility for healthcare professionals. Further research should aim at external validation and integration of these models into clinical practice.

Rapid iPSC inclusionopathy models shed light on formation, consequence, and molecular subtype of α-synuclein inclusions.

The heterogeneity of protein-rich inclusions and its significance in neurodegeneration is poorly understood. Standard patient-derived iPSC models develop inclusions neither reproducibly nor in a reasonable time frame. Here, we developed screenable iPSC "inclusionopathy" models utilizing piggyBac or targeted transgenes to rapidly induce CNS cells that express aggregation-prone proteins at brain-like levels. Inclusions and their effects on cell survival were trackable at single-inclusion resolution. Exemplar cortical neuron α-synuclein inclusionopathy models were engineered through transgenic expression of α-synuclein mutant forms or exogenous seeding with fibrils. We identified multiple inclusion classes, including neuroprotective p62-positive inclusions versus dynamic and neurotoxic lipid-rich inclusions, both identified in patient brains. Fusion events between these inclusion subtypes altered neuronal survival. Proteome-scale α-synuclein genetic- and physical-interaction screens pinpointed candidate RNA-processing and actin-cytoskeleton-modulator proteins like RhoA whose sequestration into inclusions could enhance toxicity. These tractable CNS models should prove useful in functional genomic analysis and drug development for proteinopathies.

Biomimetic Trypsin-Responsive Structure-Bridged Mesoporous Organosilica Nanomedicine for Precise Treatment of Acute Pancreatitis.

Developing strategies to target injured pancreatic acinar cells (PACs) in conjunction with primary pathophysiology-specific pharmacological therapy presents a challenge in the management of acute pancreatitis (AP). We designed and synthesized a trypsin-cleavable organosilica precursor bridged by arginine-based amide bonds, leveraging trypsin's ability to selectively identify guanidino groups on arginine via Asp189 at the active S1 pocket and cleave the carboxy-terminal (C-terminal) amide bond via catalytic triads. The precursors were incorporated into the framework of mesoporous silica nanoparticles (MSNs) for encapsulating the membrane-permeable Ca2+ chelator BAPTA-AM with a high loading content (∼43.9%). Mesenchymal stem cell membrane coating and surface modification with PAC-targeting ligands endow MSNs with inflammation recruitment and precise PAC-targeting abilities, resulting in the highest distribution at 3 h in the pancreas with 4.7-fold more accumulation than that of naked MSNs. The outcomes transpired as follows: After bioinspired MSNs' skeleton biodegradation by prematurely and massively activated trypsin, BAPTA-AM was on-demand released in injured PACs, thereby effectively eliminating intracellular calcium overload (reduced Ca2+ level by 81.3%), restoring cellular redox status, blocking inflammatory cascades, and inhibiting cell necrosis by impeding the IκBα/NF-κB/TNF-α/IL-6 and CaMK-II/p-RIP3/p-MLKL/caspase-8,9 signaling pathways. In AP mice, a single dose of the formulation significantly restored pancreatic function (lipase and amylase reduced more by 60%) and improved the survival rate from 50 to 91.6%. The formulation offers a potentially effective strategy for clinical translation in AP treatment.

Self-Sulfhydrated, Nitro-Fixed Albumin Nanoparticles as a Potent Therapeutic Agent for the Treatment of Acute Liver Injury.

Exogenous polysulfhydryls (R-SH) supplementation and nitric oxide (NO) gas molecules delivery provide essential antioxidant buffering pool components and anti-inflammatory species in cellular defense against injury, respectively. Herein, the intermolecular disulfide bonds in bovine serum albumin (BSA) molecules were reductively cleaved under native and mild conditions to expose multiple sulfhydryl groups (BSA-SH), then sulfhydryl-nitrosylated (R-SNO), and nanoprecipitated to form injectable self-sulfhydrated, nitro-fixed albumin nanoparticles (BSA-SNO NPs), allowing albumin to act as a NO donor reservoir and multiple sulfhydryl group transporter while also preventing unfavorable oxidation and self-cross-linking of polysulfhydryl groups. In two mouse models of ischemia/reperfusion-induced and endotoxin-induced acute liver injury (ALI), a single low dosage of BSA-SNO NPs (S-nitrosothiols: 4 µmol·kg-1) effectively attenuated oxidative stress and systemic inflammation cascades in the upstream pathophysiology of disease progression, thus rescuing dying hepatocytes, regulating host defense, repairing microcirculation, and restoring liver function. By mechanistically upregulating the antioxidative signaling pathway (Nrf-2/HO-1/NOQ1) and inhibiting the inflammatory cytokine storm (NF-κB/p-IκBα/TNF-α/IL-ß), BSA-SNO NPs blocked the initiation of the mitochondrial apoptotic signaling pathway (Cyto C/Bcl-2 family/caspase-3) and downregulated the cell pyroptosis pathway (NLRP3/ASC/IL-1ß), resulting in an increased survival rate from 26.7 to 73.3%. This self-sulfhydrated, nitro-fixed functionalized BSA nanoformulation proposes a potential drug-free treatment strategy for ALI.

Overexpression of LAG-3: a potential indicator of low immune function in tuberculosis.

Background: Tuberculosis (TB) persists as a global health challenge, with its treatment hampered by the side effects of long-term combination drug therapies and the growing issue of drug resistance. Therefore, the development of novel therapeutic strategies is critical. This study focuses on the role of immune checkpoint molecules (ICs) and functions of CD8+ T cells in the search for new potential targets against TB. Methods: We conducted differential expression genes analysis and CD8+ T cell functional gene analysis on 92 TB samples and 61 healthy individual (HI) samples from TB database GSE83456, which contains data on 34,603 genes. The GSE54992 dataset was used to validated the findings. Additionally, a cluster analysis on single-cell data from primates infected with mycobacterium tuberculosis and those vaccinated with BCG was performed. Results: The overexpression of LAG-3 gene was found as a potentially important characteristic of both pulmonary TB (PTB) and extrapulmonary TB (EPTB). Further correlation analysis showed that LAG-3 gene was correlated with GZMB, perforin, IL-2 and IL-12. A significant temporal and spatial variation in LAG-3 expression was observed in T cells and macrophages during TB infection and after BCG vaccination. Conclusion: LAG-3 was overexpressed in TB samples. Targeting LAG-3 may represent a potential therapeutic target for tuberculosis.

Design of multi-epitope vaccine against porcine rotavirus using computational biology and molecular dynamics simulation approaches.

Porcine Rotavirus (PoRV) is a significant pathogen affecting swine-rearing regions globally, presenting a substantial threat to the economic development of the livestock sector. At present, no specific pharmaceuticals are available for this disease, and treatment options remain exceedingly limited. This study seeks to design a multi-epitope peptide vaccine for PoRV employing bioinformatics approaches to robustly activate T-cell and B-cell immune responses. Two antigenic proteins, VP7 and VP8*, were selected from PoRV, and potential immunogenic T-cell and B-cell epitopes were predicted using immunoinformatic tools. These epitopes were further screened according to non-toxicity, antigenicity, non-allergenicity, and immunogenicity criteria. The selected epitopes were linked with linkers to form a novel multi-epitope vaccine construct, with the PADRE sequence (AKFVAAWTLKAAA) and RS09 peptide attached at the N-terminus of the designed peptide chain to enhance the vaccine's antigenicity. Protein-protein docking of the vaccine constructs with toll-like receptors (TLR3 and TLR4) was conducted using computational methods, with the lowest energy docking results selected as the optimal predictive model. Subsequently, molecular dynamics (MD) simulation methods were employed to assess the stability of the protein vaccine constructs and TLR3 and TLR4 receptors. The results indicated that the vaccine-TLR3 and vaccine-TLR4 docking models remained stable throughout the simulation period. Additionally, the C-IMMSIM tool was utilized to determine the immunogenic triggering capability of the vaccine protein, demonstrating that the constructed vaccine protein could induce both cell-mediated and humoral immune responses, thereby playing a role in eliciting host immune responses. In conclusion, this study successfully constructed a multi-epitope vaccine against PoRV and validated the stability and efficacy of the vaccine through computational analysis. However, as the study is purely computational, experimental evaluation is required to validate the safety and immunogenicity of the newly constructed vaccine protein.

Salinity-induced variations in bacterial composition and co-occurrence patterns within Salicornia-based constructed wetlands in mariculture.

Constructed wetlands use vegetation and microorganisms to remove contaminants like nitrogen and phosphorus from water. For mariculture, the impact of salinity on the efficiency of wastewater treatment of wetlands is unneglectable. However, little is known about their impact on the microbiome in constructed wetlands. Here, we set four salinity levels (15, 22, 29, and 36) in Salicornia constructed wetlands, and the experiment was conducted for a period of 72 days. The 15 group exhibited the highest removal rates of nitrogen compounds and phosphate, compared to the other salinity groups, the nosZ gene exhibited significantly higher expression in the 22 group (p < 0.05), indicated that microorganisms in 22 salinity have higher denitrification abilities. The three dominant phyla identified within the microbiomes were Proteobacteria, known for their diverse metabolic capabilities; Cyanobacteria, important for photosynthesis and nitrogen fixation; and Firmicutes, which include many fermenters. The ecological network analysis revealed a 'small world' model, characterized by high interconnectivity and short path lengths between microbial species, and had higher co-occurrence (45.13%) observed in this study comparing to the Erdös-Réyni random one (32.35%). The genus Microbulbifer emerged as the sole connector taxon, pivotal for integrating different microbial communities involved in nitrogen removal. A negative correlation was observed between salinity levels and network complexity, as assessed by the number of connections and diversity of interactions within the microbial community. Collectively, these findings underscore the critical role of microbial community interactions in optimizing nitrogen removal in constructed wetlands, with potential applications in the design and management of such systems for improved wastewater treatment in mariculture.

Additive manufacturing of degradable metallic scaffolds for material-structure-driven diabetic maxillofacial bone regeneration.

The regeneration of maxillofacial bone defects associated with diabetes mellitus remains challenging due to the occlusal loading and hyperglycemia microenvironment. Herein, we propose a material-structure-driven strategy through the additive manufacturing of degradable Zn-Mg-Cu gradient scaffolds. The in situ alloying of Mg and Cu endows Zn alloy with admirable compressive strength for mechanical support and uniform degradation mode for preventing localized rupture. The scaffolds manifest favorable antibacterial, angiogenic, and osteogenic modulation capacity in mimicked hyperglycemic microenvironment, and Mg and Cu promote osteogenic differentiation in the early and late stages, respectively. In addition, the scaffolds expedite diabetic maxillofacial bone ingrowth and regeneration by combining the metabolic regulation effect of divalent metal cations and the hyperboloid and suitable permeability of the gradient structure. RNA sequencing further reveals that RAC1 might be involved in bone formation by regulating the transport and uptake of glucose related to GLUT1 in osteoblasts, contributing to cell function recovery. Inspired by bone healing and structural cues, this study offers an essential understanding of the designation and underlying mechanisms of the material-structure-driven strategy for diabetic maxillofacial bone regeneration.

Habitat selection drives diatom community assembly and network complexity in sediment-laden riverine environments.

Microbial communities assemble stochastically and deterministically, but how different assembly processes shape diatom community structure across riverine habitats is unclear, especially in sediment-laden environments. In this study, we deciphered the mechanisms of riverine diatom community assembly in the water column and riverbed substrate with varying sediment concentrations. Water and sediment samples were collected from 44 sampling sites along the Yellow River mainstream during two seasons. Diatom communities were characterized based on high-throughput sequencing of the 18S ribosomal RNA genes coupled with multivariate statistical analyses. A total of 198 diatom species were taxonomically assigned, including 182 free-living and particle-attached species and 184 surface-sediment species. Planktonic communities were structurally different from benthic communities, with Cyclotella being dominant mainly in the middle and lower reaches of the river with higher sediment concentrations. Both stochastic and deterministic processes affected diatom community assembly in different habitats. Species dispersal was more important in the water than in the substrate, and this process was strengthened by increased sediment concentration across habitats. Diatom communities exhibited lower network complexity and enhanced antagonistic or competitive interactions between species in response to higher sediment concentrations compared with lower sediment concentrations mainly in the source region of the river. Differences in the species composition and community diversity of planktonic diatoms were closely correlated with the proportion of bare land area, nitrogen nutrients, precipitation, and sediment concentration. In particular, particle-attached diatoms responded sensitively to environmental factors. These findings provide strong evidence for sediment-mediated assembly and interactions of riverine diatom communities.

Exploring the interplay between triple-negative breast cancer stem cells and tumor microenvironment for effective therapeutic strategies.

Triple-negative breast cancer (TNBC) is a highly aggressive and metastatic malignancy with poor treatment outcomes. The interaction between the tumor microenvironment (TME) and breast cancer stem cells (BCSCs) plays an important role in the development of TNBC. Owing to their ability of self-renewal and multidirectional differentiation, BCSCs maintain tumor growth, drive metastatic colonization, and facilitate the development of drug resistance. TME is the main factor regulating the phenotype and metastasis of BCSCs. Immune cells, cancer-related fibroblasts (CAFs), cytokines, mesenchymal cells, endothelial cells, and extracellular matrix within the TME form a complex communication network, exert highly selective pressure on the tumor, and provide a conducive environment for the formation of BCSC niches. Tumor growth and metastasis can be controlled by targeting the TME to eliminate BCSC niches or targeting BCSCs to modify the TME. These approaches may improve the treatment outcomes and possess great application potential in clinical settings. In this review, we summarized the relationship between BCSCs and the progression and drug resistance of TNBC, especially focusing on the interaction between BCSCs and TME. In addition, we discussed therapeutic strategies that target the TME to inhibit or eliminate BCSCs, providing valuable insights into the clinical treatment of TNBC.

Nkx1.2 deletion decreases fat production in zebrafish.

OBJECTIVE: This study aimed to investigate the role of Nkx1-2, a transcription factor with the NK homeobox domain, in the regulation of fat production. METHODS: Gene expression was analyzed using quantitative real-time polymerase chain reaction or transcriptome sequencing. CRISPR/Cas9 technology was employed to generate nkx1.2 knockout zebrafish and nkx1.2-deleted 3T3-L1 cells. Lipid droplet production in zebrafish larvae was visually quantified using Nile red staining, whereas lipid droplets in 3T3-L1 cells were stained with Oil red O. The binding of Nkx1-2 to the promoter was verified through an electrophoretic mobility shift assay experiment. RESULTS: Nkx1-2 plays crucial roles in the regulation of fat production in zebrafish. Knockout of nkx1.2 in zebrafish leads to weight loss, accompanied by significantly reduced lipid droplet production and decreased visceral and liver fat content. Furthermore, genes related to lipid biosynthesis are significantly downregulated. In 3T3-L1 preadipocytes, Nkx1-2 induces differentiation into mature adipocytes by binding to the cebpa promoter, thereby activating its transcription. Additionally, the expression of nkx1.2 is regulated by the p38 MAPK, JNK, or Smad2/3 signaling pathways in 3T3-L1 cells. CONCLUSIONS: Our findings suggest that Nkx1-2 functions as a positive regulator of fat production, playing a critical role in adipocyte differentiation and lipid biosynthesis.

Emodin improves renal fibrosis in chronic kidney disease by regulating mitochondrial homeostasis through the mediation of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α).

Chronic kidney disease (CKD) is a leading public health issue associated with high morbidity worldwide. However, there are only a few effective therapeutic strategies for CKD. Emodin, an anthraquinone compound from rhubarb, can inhibit fibrosis in tissues and cells. Our study aims to investigate the antifibrotic effect of emodin and the underlying molecular mechanism. A unilateral ureteral obstruction (UUO)-induced rat model was established to evaluate the effect of emodin on renal fibrosis development. Hematoxylin and eosin staining, Masson's trichrome staining, and immunohistochemistry staining were performed to analyze histopathological changes and fibrotic features after emodin treatment. Subsequently, a transforming growth factor-beta 1 (TGF-ß1)-induced cell model was used to assess the inhibition of emodin on cell fibrosis in vitro. Furthermore, Western blot analysis and real-time quantitative reverse transcription-polymerase chain reaction were performed to validate the regulatory mechanism of emodin on renal fibrosis progression. As a result, emodin significantly improved histopathological abnormalities in rats with UUO. The expression of fibrosis biomarkers and mitochondrial biogenesis-related proteins also decreased after emodin treatment. Moreover, emodin blocked TGF-ß1-induced fibrotic phenotype, lipid accumulation, and mitochondrial homeostasis in NRK-52E cells. Conversely, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) silencing significantly reversed these features in emodin-treated cells. Collectively, emodin plays an important role in regulating PGC-1α-mediated mitochondria function and energy homeostasis. This indicates that emodin exhibits great inhibition against renal fibrosis and acts as a promising inhibitor of CKD.

Unlocking the NIR-II AIEgen for High Brightness through Intramolecular Electrostatic Locking.

Fluorescent imaging and biosensing in the near-infrared-II (NIR-II) window holds great promise for non-invasive, radiation-free, and rapid-response clinical diagnosis. However, it's still challenging to develop bright NIR-II fluorophores. In this study, we report a new strategy to enhance the brightness of NIR-II aggregation-induced emission (AIE) fluorophores through intramolecular electrostatic locking. By introducing sulfur atoms into the side chains of the thiophene bridge in TSEH molecule, the molecular motion of the conjugated backbone can be locked through intramolecular interactions between the sulfur and nitrogen atoms. This leads to enhanced NIR-II fluorescent emission of TSEH in both solution and aggregation states. Notably, the encapsulated nanoparticles (NPs) of TSEH show enhanced brightness, which is 2.6-fold higher than TEH NPs with alkyl side chains. The in vivo experiments reveal the feasibility of TSEH NPs in vascular and tumor imaging with a high signal-to-background ratio and precise resection for tiny tumors. In addition, polystyrene nanospheres encapsulated with TSEH are utilized for antigen detection in lateral flow assays, showing a signal-to-noise ratio 1.9-fold higher than the TEH counterpart in detecting low-concentration antigens. This work highlights the potential for developing bright NIR-II fluorophores through intramolecular electrostatic locking and their potential applications in clinical diagnosis and biomedical research.

Integrating bulk and single-cell sequencing data to construct a Scissor+ dendritic cells prognostic model for predicting prognosis and immune responses in ESCC.

Esophageal squamous cell carcinoma (ESCC) is characterized by molecular heterogeneity with various immune cell infiltration patterns, which have been associated with therapeutic sensitivity and resistance. In particular, dendritic cells (DCs) are recently discovered to be associated with prognosis and survival in cancer. However, how DCs differ among ESCC patients has not been fully comprehended. Recently, the advance of single-cell RNA sequencing (scRNA-seq) enables us to profile the cell types, states, and lineages in the heterogeneous ESCC tissues. Here, we dissect the ESCC tumor microenvironment at high resolution by integrating 192,078 single cells from 60 patients, including 4379 DCs. We then used Scissor, a method that identifies cell subpopulations from single-cell data that are associated bulk samples with genomic and clinical information, to stratify DCs into Scissorhi and Scissorlow subtypes. We applied the Scissorhi gene signature to stratify ESCC scRNAseq patient, and we found that PD-L1, TIGIT, PVR and IL6 ligand-receptor-mediated cell interactions existed mainly in Scissorhi patients. Finally, based on the Scissor results, we successfully developed a validated prognostic risk model for ESCC and further validated the reliability of the risk prediction model by recruiting 40 ESCC clinical patients. This information highlights the importance of these genes in assessing patient prognosis and may help in the development of targeted or personalized therapies for ESCC.

Donor-Acceptor Modulating of Ionic AIE Photosensitizers for Enhanced ROS Generation and NIR-II Emission.

Photosensitizers (PSs) with aggregation-induced emission (AIE) characteristics are competitive candidates for bioimaging and therapeutic applications. However, their short emission wavelength and nonspecific organelle targeting hinder their therapeutic effectiveness. Herein, a donor-acceptor modulation approach is reported to construct a series of ionic AIE photosensitizers with enhanced photodynamic therapy (PDT) outcomes and fluorescent emission in the second near-infrared (NIR-II) window. By employing dithieno[3,2-b:2',3'-d]pyrrole (DTP) and indolium (In) as the strong donor and acceptor, respectively, the compound DTP-In exhibits a substantial redshift in absorption and fluorescent emission reach to NIR-II region. The reduced energy gap between singlet and triplet states in DTP-In also increases the reactive oxygen species (ROS) generation rate. Further, DTP-In can self-assemble in aqueous solutions, forming positively charged nanoaggregates, which are superior to conventional encapsulated nanoparticles in cellular uptake and mitochondrial targeting. Consequently, DTP-In aggregates show efficient photodynamic ablation of 4T1 cancer cells and outstanding tumor theranostic in vivo under 660 nm laser irradiation. This work highlights the potential of molecular engineering of donor-acceptor AIE PSs with multiple functionalities, thereby facilitating the development of more effective strategies for cancer therapy.