Macrophage biomimetic nanoparticle-targeted functional extracellular vesicle micro-RNAs revealed via multiomics analysis alleviate sepsis-induced acute lung injury.

Patients who suffer from sepsis typically experience acute lung injury (ALI). Extracellular vesicles (EVs) contain miRNAs, which are potentially involved in ALI. However, strategies to screen more effective EV-miRNAs as therapeutic targets are yet to be elucidated. In this study, functional EV-miRNAs were identified based on multiomics analysis of single-cell RNA sequencing of targeted organs and serum EV (sEV) miRNA profiles in patients with sepsis. The proportions of neutrophils and macrophages were increased significantly in the lungs of mice receiving sEVs from patients with sepsis compared with healthy controls. Macrophages released more EVs than neutrophils. MiR-125a-5p delivery by sEVs to lung macrophages inhibited Tnfaip3, while miR-221-3p delivery to lung neutrophils inhibited Fos. Macrophage membrane nanoparticles (MM NPs) loaded with an miR-125a-5p inhibitor or miR-221-3p mimic attenuated the response to lipopolysaccharide (LPS)-induced ALI. Transcriptome profiling revealed that EVs derived from LPS-stimulated bone marrow-derived macrophages (BMDMs) induced oxidative stress in neutrophils. Blocking toll-like receptor, CXCR2, or TNFα signaling in neutrophils attenuated the oxidative stress induced by LPS-stimulated BMDM-EVs. This study presents a novel method to screen functional EV-miRNAs and highlights the pivotal role of macrophage-derived EVs in ALI. MM NPs, as delivery systems of key sEV-miRNA mimics or inhibitors, alleviated cellular responses observed in sepsis-induced ALI. This strategy can be used to reduce septic organ damage, particularly lung damage, by targeting EVs.

Quantitative reconstruction of a single super rainstorm using daily resolved δ18O of land snail shells.

A "once-in-a-millennium" super rainstorm battered Zhengzhou, central China, from 07/17/2021 to 07/22/2021 (named "7.20" Zhengzhou rainstorm). It killed 398 people and caused billions of dollars in damage. A pressing question is whether rainstorms of this intensity can be effectively documented by geological archives to understand better their historical variabilities beyond the range of meteorological data. Here, four land snail shells were collected from Zhengzhou, and weekly to daily resolved snail shell δ18O records from June to September of 2021 were obtained by gas-source mass spectrometry and secondary ion mass spectrometry. The daily resolved records show a dramatic negative shift between 06/18/2021 and 09/18/2021, which has been attributed to the "7.20" Zhengzhou rainstorm. Moreover, the measured amplitude of this shift is consistent with the theoretical value estimated from the flux balance model and instrumental data for the "7.20" Zhengzhou rainstorm. Our results suggest that the ultra-high resolution δ18O of land snail shells have the potential to reconstruct local synoptic scale rainstorms quantitatively, and thus fossil snail shells in sedimentary strata can be valuable material for investigating the historical variability of local rainstorms under different climate backgrounds.

Utilization of Pickering emulsion stabilized by chitin nanofibers for improving water and oxygen resistance of gelatin films.

The hydrophilicity of gelatin films obviously limits their application. In this work, novel protonated chitin nanofiber was prepared with green methods, surficial deacetylation combined with acidic and mechanical treatment. Composite films with excellent water and oxygen barrier properties were successfully prepared by blending O/W Pickering emulsions stabilized by chitin nanofibers with gelatin substrates. The films were characterized by Fourier-transform infrared, X-ray diffraction, mechanical properties, water and oxygen permeability, moisture content, water solubility, water contact angle and optical properties. The results demonstrated that the amino groups of chitin nanofibers bound to the carboxyl groups of gelatin via electrostatic interactions, which contributing to the excellent mechanical and barrier properties of composite films. The elongation at break of composite film (the concentration of chitin nanofiber was 0.2 wt%) was 2.66 times of gelatin film. And the water vapor and oxygen permeability of composite films lowered to 65.9 % and 52.9 %, respectively. The introduction of O/W Pickering emulsion significantly enhanced the hydrophobicity of gelatin-based film and the chitin nanofibers played a positive role in stabilizing the gelatin chains to a certain extent. This study expands the application fields of gelatin-based films and provides valuable technical route for the preparation of barrier films.

Stability and 3D-printing performance of high-internal-phase emulsions based on ultrafine soybean meal particles.

There are numerous studies on the application of soybean whey protein in three-dimensional (3D) printing. In this study, the effects of soybean meal particles (5%, 6%, 7%, 8%, 9%, and 10%) and oil-phase concentrations (70%, 72%, 74%, 76%, and 78%) on the stability and 3D-printing performance of a soybean-meal-based high-internal-phase emulsion were investigated. The results showed that the particle size of the emulsion decreased with increasing soybean meal particle concentration, and that increasing the concentration of the oil phase improved the viscoelasticity of the emulsion. Rheological tests further showed that the higher storage modulus of the emulsion indicated better support and stability. The emulsion with 8% soybean meal-particles and 76% oil-phase concentration exhibited the best printing effect. This study provides an effective solution for the preparation of stabilized high-internal-phase emulsions of soybean meal particles suitable for 3D printing.

Stability and Bioaccessibility of Quercetin-Enriched Pickering Emulsion Gels Stabilized by Cellulose Nanocrystals Extracted from Rice Bran.

To investigate the optimal delivery system of quercetin, in this paper, cellulose nanocrystals (CNCs) extracted from rice bran were used to stabilize the Pickering emulsion and Pickering emulsion gels (PEGs) with quercetin. To compare the emulsion properties, stability, antioxidation activity, encapsulation rate, and bioaccessibility of the quercetin, four emulsions of CNC Pickering emulsion (C), CNC Pickering emulsion with quercetin (CQ), CNC Pickering gel emulsion (CG), and CNC Pickering gel emulsions with quercetin (CQG) were prepared. All four emulsions exhibited elastic gel network structure and good stability. The quercetin significantly reduced the particle size, increased the stability, and improved the antioxidant capacity of CQ and CQG. Compared to C and CG, the ABTS+ radical scavenging capacities of CQ and CQG were respectively enhanced by 46.92% and 3.59%. In addition, CQG had a higher encapsulation rate at 94.57% and higher bioaccessibility (16.17) compared to CQ. This study not only indicated that CNC from rice bran could be exploited as an excellent stabilization particle for Pickering emulsions, but also provided a highly stable and bioaccessible delivery system for water-insoluble functional active factors.

Distribution and Drug Resistance of Common Pathogens Causing Lower Respiratory Tract Infection in Xinjiang Region.

Objective: This study aims to analyze the composition and distribution of pathogenic bacteria in lower respiratory tract infections (LRTI) and their antimicrobial resistance patterns in a hospital in Xinjiang, to guide more effective antibiotic selection and inform clinical management. Methods: We retrospectively analyzed 545 strains isolated from various clinical specimens like sputum and blood, collected between June 2020 and June 2023, using the LIST system. The strains were subjected to drug resistance testing, and statistical analyses included t tests and Chi-square tests. Results: Among gram-negative bacilli, Acinetobacter baumannii dominated, accounting for 32.11%, followed by Pseudomonas aeruginosa, accounting for 18.35%. Among gram-positive bacteria, thrombin-negative staphylococcus was at the top of the list, followed by Staphylococcus aureus. Among Acinetobacter baumannii (AB), carbapenem-resistant Acinetobacter baumannii plays a dominant role. The sensitivity rate of these strains to tigecycline and amikacin could reach more than 80%. The sensitivity of Pseudomonas aeruginosa (PA) to piperacillin, gentamicin, imipenem, meropenem, ciprofloxacin and levofloxacin ranged from 50% to 80%. It is worth mentioning that the sensitivity rate of PA to amikacin, cefoperazone, and tobramycin exceeded 80%. Amikacin was more than 60% sensitive to carbapenem, ß-lactam inhibitors, tigecycline, quinolones, and aminoglycosides of ESBL producing Klebsiella pneumoniae. Among gram-positive coccus, methicillin-resistant coagulase-negative staphylococcus was 100% sensitive to duration, e, tigecycline, and vancomycin. In addition, the susceptibility rate of these strains to rifampicin and linezolid was greater than 70%. Conclusions: In patients with lower respiratory tract infection (LRTI) in a hospital in Xinjiang, the most common pathogenic bacteria are gram-negative bacilli, mainly Acinetobacter baumannii and Pseudomonas aeruginosa. Both resistant and non-resistant strains showed sensitivity to amikacin and tigecycline. Additionally, staphylococcus accounted for half of the total number of gram-positive bacteria, among which methicillin-resistant strains were more sensitive to vancomycin and linezolid.

Preparation of high-resolution micro/nano dot array by electrohydrodynamic jet printing with enhanced uniformity.

The high-resolution array is the basic structure of most kinds of microelectronics. Electrohydrodynamic jet (E-Jet) printing technology is widely applied in manufacturing array structures with high resolution, high material compatibility and multi-modal printing. It is still challenging to acquire high uniformity of printed array with micro-nanometer resolution, which greatly influences the performance and lifetime of the microelectronics. In this paper, to improve the uniformity of the printed array, the influence of each parameter on the uniformity of the E-jet printed dot array is studied on the cobuilt NEJ-E/P200 experimental platform, finding the applied voltage plays the most important role in maintaining the uniformity of the printed array. By appropriately adjusting the printing parameters, the dot arrays with different resolutions from 500 pixels per inch (PPI) to 17,000 PPI are successfully printed. For arrays below and over 10,000 PPI, the deviations of the uniformity are within 5% and 10% respectively. In this work, the dot array over 15,000 PPI is first implemented using E-jet printing. The conclusions acquired by experimental analysis of dot array printing process are of great importance in high resolution array printing as it provides practical guidance for parameters adjustment.

Intracellular Protein Adsorption Behavior and Biological Effects of Polystyrene Nanoplastics in THP-1 Cells.

Micro(nano)plastics (MNPs) are emerging pollutants that can adsorb pollutants in the environment and biological molecules and ultimately affect human health. However, the aspects of adsorption of intracellular proteins onto MNPs and its biological effects in cells have not been investigated to date. The present study revealed that 100 nm polystyrene nanoplastics (NPs) could be internalized by THP-1 cells and specifically adsorbed intracellular proteins. In total, 773 proteins adsorbed onto NPs with high reliability were identified using the proteomics approach and analyzed via bioinformatics to predict the route and distribution of NPs following cellular internalization. The representative proteins identified via the Kyoto Encyclopedia of Genes and Genomes pathway analysis were further investigated to characterize protein adsorption onto NPs and its biological effects. The analysis revealed that NPs affect glycolysis through pyruvate kinase M (PKM) adsorption, trigger the unfolded protein response through the adsorption of ribophorin 1 (RPN1) and heat shock 70 protein 8 (HSPA8), and are chiefly internalized into cells through clathrin-mediated endocytosis with concomitant clathrin heavy chain (CLTC) adsorption. Therefore, this work provides new insights and research strategies for the study of the biological effects caused by NPs.

Reconstruction of ENSO variability using the standardized growth index of a Tridacna shell from Yongshu Reef, South China Sea.

El Niño-Southern Oscillation (ENSO) is the strongest signal of global interannual climate anomaly and reconstructing past ENSO variations using high-resolution paleoclimate archives can improve our understanding of ENSO variability, as well as improve our ability to predict future climate changes. Here, a daily resolution standardized growth index (SGI) was established using a giant clam (Tridacna spp.) shell specimen MD2 (life span: 1994-2013 CE), collected from the Yongshu Reef, southern South China Sea (SCS). The cross-spectral and correlation analysis indicated that the SGI variation of MD2 was strongly influenced by ENSO variability on an interannual timescale. Tridacna spp. is in symbiosis with zooxanthellae, and its growth index is usually modulated by the photosynthetic efficiency of zooxanthellae. During the El Niño (La Niña) period, the convective anomalies stimulated in western Pacific would increase (decrease) the effective solar radiation on Yongshu Reef, and in turn influence the photosynthesis rate of zooxanthellae and enzyme activity for the calcification site and thus the SGI of giant clam MD2. The SGI can explain 54.7 % of ENSO variance, demonstrating the potential for Tridacna SGI in ENSO reconstruction. Compared with conventional ENSO reconstruction using high-resolution geochemical proxies, the method of giant clam SGI is rapid and economical.

GBP2 upregulated in LPS-stimulated macrophages-derived exosomes accelerates septic lung injury by activating epithelial cell NLRP3 signaling.

Macrophages infiltration is a crucial factor causing Sepsis-associated acute lung injury (ALI). Accumulating evidence suggests macrophages-alveolar epithelial cells communication is proven to be critical in ALI. However, little is known regarding how activated macrophages regulated sepsis-associated ALI. To explore the role of macrophages-alveolar epithelial cells communication in the ALI process, our data revealed that Lipopolysaccharides-induced macrophages-derived exosomes (L-Exo) induced sepsis-associated ALI and caused alveolar epithelial cells damage. Moreover, Guanylate-binding protein 2 (GBP2) was significantly upregulated in L-Exo, and NLRP3 inflammasomes was the direct target of GBP2. Further experimentation showed that GBP2 inhibition in vitro and in vivo reserves L-Exo effects, while GBP2 overexpression in vitro and in vivo promotes L-Exo effects. These results demonstrated that L-Exo contains excessive GBP2 and promotes inflammation through targeting NLRP3 inflammasomes, which induced alveolar epithelial cells dysfunction and pyroptosis. These findings demonstrate that L-Exo exerted a deleterious effect on ALI by regulating the GBP2/NLRP3 axis, which might provide new insight on ALI prevention and treatment.

Transcriptomic Analysis of THP-1 Cells Exposed by Monosodium Urate Reveals Key Genes Involved in Gout.

BACKGROUND: Gout is a common inflammatory arthritis, which is mainly caused by the deposition of monosodium urate (MSU) in tissues. Transcriptomics was used to explore the pathogenesis and treatment of gout in our work. OBJECTIVE: The objective of the study was to analyze and validate potential therapeutic targets and biomarkers in THP-1 cells that were exposed to MSU. METHODS: THP-1 cells were exposed to MSU. The inflammatory effect was characterized, and RNA-Seq analysis was then carried out. The differential genes obtained by RNA-Seq were analyzed with gene expression omnibus (GEO) series 160170 (GSE160170) gout-related clinical samples in the GEO database and gout-related genes in the GeneCards database. From the three analysis approaches, the genes with significant differences were verified by the differential genes' transcription levels. The interaction relationship of long non-coding RNA (lncRNA) was proposed by ceRNA network analysis. RESULTS: MSU significantly promoted the release of IL-1ß and IL-18 in THP-1 cells, which aggravated their inflammatory effect. Through RNA-Seq, 698 differential genes were obtained, including 606 differential mRNA and 92 differential `LncRNA. Cross-analysis of the RNA-Seq differential genes, the GSE160170 differential genes, and the gout-related genes in GeneCards revealed a total of 17 genes coexisting in the tripartite data. Furthermore, seven differential genes-C-X-C motif chemokine ligand 8 (CXCL8), C-X-C motif chemokine ligand 2 (CXCL2), tumor necrosis factor (TNF), C-C motif chemokine ligand 3 (CCL3), suppressor of cytokine signaling 3 (SOCS3), oncostatin M (OSM), and MIR22 host gene (MIR22HG)-were verified as key genes that analyzed the weight of genes in pathways, the enrichment of inflammationrelated pathways, and protein-protein interaction (PPI)nodes combined with the expression of genes in RNA-Seq and GSE160170. It is suggested that MIR22HG may regulate OSM and SOCS3 through microRNA 4271 (miR-4271), OSM, and SOCS3m; CCL3 through microRNA 149-3p (miR-149-3p); and CXCL2 through microRNA 4652-3p (miR-4652-3p). CONCLUSION: The potential of CXCL8, CXCL2, TNF, CCL3, SOCS3, and OSM as gout biomarkers and MIR22HG as a therapeutic target for gout are proposed, which provide new insights into the mechanisms of gout biomarkers and therapeutic methods.

Structure and surface properties of ozone-conjugated octenyl succinic anhydride modified waxy rice starch: Towards high-stable Pickering emulsion.

In the present work, a dual-modified waxy rice starch (OOWRS) fabricated with OSA and ozone was successfully used to stabilize the O/W Pickering emulsion. The molecular structure, surface properties, and underlying stabilizing mechanism were systematically investigated. The results showed that oxidation occurring on the surface of OSA-modified waxy rice starch (OSAWRS) resulted in the presence of indentations and cracks. The relative crystallinity of starch was generally decreased with increasing degree of oxidation. Due to the introduction of carbonyl and the variation in surface structure, the hydrophobicity and acidity of OSAWRS were significantly enhanced after the ozone treatment. Remarkably, OOWRS stabilized Pickering emulsion exhibited a feature of typical O/W emulsion, and the 0.5 h and 1 h OOWRS emulsion exhibited a more uniform droplet size as well as a higher surface potential. We also noted that a weak-gel network was formed within the OOWRS emulsion system as the hydrophilic starch chains played a bridging role. Two reasons for the improved stability of the emulsion were the special gel structure and the enhanced electrical repulsion among the droplets. This research provides that ozone-conjugated OSA modification is a promising strategy for improving the emulsion ability of starch-based Pickering emulsions.

An ecological assessment of the potential pandemic threat of Dengue Virus in Zhejiang province of China.

BACKGROUND AND AIM: Dengue fever, transmitted by Aedes mosquitoes, is a significant public health concern in tropical and subtropical regions. With the end of the COVID-19 pandemic and the reopening of the borders, dengue fever remains a threat to mainland China, Zhejiang province of China is facing a huge risk of importing the dengue virus. This study aims to analyze and predict the current and future potential risk regions for Aedes vectors distribution and dengue prevalence in Zhejiang province of China. METHOD: We collected occurrence records of DENV and DENV vectors globally from 2010 to 2022, along with historical and future climate data and human population density data. In order to predict the probability of DENV distribution in Zhejiang province of China under future conditions, the ecological niche of Ae. aegypti and Ae. albopictus was first performed with historical climate data based on MaxEnt. Then, predicted results along with a set of bioclimatic variables, elevation and human population density were included in MaxEnt model to analyze the risk region of DENV in Zhejiang province. Finally, the established model was utilized to predict the spatial pattern of DENV risk in the current and future scenarios in Zhejiang province of China. RESULTS: Our findings indicated that approximately 89.2% (90,805.6 KM2) of Zhejiang province of China is under risk, within about 8.0% (8,144 KM2) classified as high risk area for DENV prevalence. Ae. albopictus were identified as the primary factor influencing the distribution of DENV. Future predictions suggest that sustainable and "green" development pathways may increase the risk of DENV prevalence in Zhejiang province of China. Conversely, Fossil-fueled development pathways may reduce the risk due to the unsuitable environment for vectors. CONCLUSIONS: The implications of this research highlight the need for effective vector control measures, community engagement, health education, and environmental initiatives to mitigate the potential spread of dengue fever in high-risk regions of Zhejiang province of China.

Preparation of magnetically separable and low-cost MC-FePd3NPs with enhanced catalytic activity in the reduction of p-nitrophenol.

To obtain a magnetically separable, low-cost and highly efficient reduction catalyst, microbial carbon-loaded bimetallic palladium/iron nanoparticles (MC-FePd3NPs) were synthesized in this study by using waste yeast residue doped with iron during the preparation process of microbial carbon-loaded monometallic palladium nanoparticles (MC-Pd NPs). The morphology, crystal structure, magnetic properties and catalytic performance of MC-FePd3NPs for the reduction ofp-nitrophenol (p-NP) were investigated by various characterization techniques, such as SEM-EDS, TEM, XRD, PPMS-9 and UV-vis spectroscopy. The catalytic experiments showed that the MC-FePd3NPs prepared under pyrolysis conditions at 700 °C had an apparent rate constant of 1.85 × 10-1s-1which is better than the rate constants of MC-Pd NPs and other palladium-based nanocatalytic materials reported so far. The amount of palladium used in the synthesis of MC-FePd3NPs was half that of MC-Pd NPs. The catalyst exhibited soft magnetic ordering behavior and still showed a catalytic efficiency of 97.4% after five consecutive reaction cycles. Furthermore, employing MC-FePd3NPs reduces the costs of catalyst preparation and use in production. MC-FePd3NPs with efficient catalytic properties, facile magnetic separation and recyclability, and low costs of preparation and use have considerable potential for industrial applications.

HPV18 E6 inhibits α-ketoglutarate-induced pyroptosis of esophageal squamous cell carcinoma cells via the P53/MDH1/ROS/GSDMC pathway.

Oncogene E6 plays a critical role in the development and progression of esophageal cancer caused by human papillomavirus (HPV) infection. Alpha-ketoglutarate (AKG) is a key metabolite in the tricarboxylic acid cycle and has been widely used as a dietary and anti-ageing supplement. In this study, we found that treating esophageal squamous carcinoma cells with a high dose of AKG can induce cell pyroptosis. Furthermore, our research confirms that HPV18 E6 inhibits AKG-induced pyroptosis of esophageal squamous carcinoma cells by lowering P53 expression. P53 downregulates malate dehydrogenase 1 (MDH1) expression; however, MDH1 downregulates L-2-hydroxyglutarate (L-2HG) expression, which inhibits a rise in reactive oxygen species (ROS) levels-as L-2HG is responsible for excessive ROS. This study reveals the actuating mechanism behind cell pyroptosis of esophageal squamous carcinoma cells induced by high concentrations of AKG, and we posit the molecular pathway via which the HPV E6 oncoprotein inhibits cell pyroptosis.

Biofunctionalization of HMX with Peptides via Polydopamine Crosslinking for Assembling an HMX@Al@CuO Nanoenergetic Composite.

Biological approaches for the synthesis of a hybrid explosive-nanothermite energetic composite have attracted greater scientific attention because of their advantages, including their moderate reactions and the absence of secondary pollution. In this study, a simple technique was developed to fabricate a hybrid explosive-nanothermite energetic composite based on a peptide and a mussel-inspired surface modification. Polydopamine (PDA) was easily imprinted onto the HMX, where it maintained its reactivity and was capable of reacting with a specific peptide used to introduce Al and CuO NPs to the surface of the HMX via specific recognition. The hybrid explosive-nanothermite energetic composites were characterized using differential scanning calorimetry (TG-DSC), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy(XPS), and a fluorescence microscope. A thermal analysis was utilized to investigate the energy-release properties of the materials. The HMX@Al@CuO, which benefitted from an enhanced interfacial contact in comparison with the physically mixed sample (HMX-Al-CuO), demonstrated a 41% lower HMX activation energy.

Bioinformatics Analysis and Verification of Metabolic Abnormalities in Esophageal Squamous Carcinoma.

BACKGROUND: Although esophageal carcinoma (EC) is one of the most common cancers in the world, details of its pathogenesis remain unclear. Metabolic reprogramming is a main feature of EC. Mitochondrial dysfunction, especially the decrease in mitochondrial complex I (MTCI), plays an important role in the occurrence and development of EC. OBJECTIVE: The objective of the study was to analyze and validate the metabolic abnormalities and the role of MTCI in esophageal squamous cell carcinoma. METHODS: In this work, we collected transcriptomic data from 160 esophageal squamous carcinoma samples and 11 normal tissue samples from The Cancer Genome Atlas (TCGA). The OmicsBean and GEPIA2 were used to conduct an analysis of differential gene expression and survival in clinical samples. Rotenone was used to inhibit the MTCI activity. Subsequently, we detected lactate production, glucose uptake, and ATP production. RESULTS: A total of 1710 genes were identified as being significantly differentially expressed. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis suggested that these differentially expressed genes (DEGs) were significantly enriched in various pathways related to carcinoma tumorigenesis and progression. Moreover, we further identified abnormalities in metabolic pathways, in particular, the significantly low expression of multiple subunits of MTCI genes (ND1, ND2, ND3, ND4, ND4L, ND5, and ND6). Rotenone was used to inhibit the MTCI activity of EC109 cells, and it was found that the decrease in MTCI activity promoted HIF1A expression, glucose consumption, lactate production, ATP production, and cell migration. CONCLUSION: Our results indicated the occurrence of abnormal metabolism involving decreased mitochondrial complex I activity and increased glycolysis in esophageal squamous cell carcinoma (ESCC), which might be related to its development and degree of malignancy.

ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes.

Phase transitions of cellular proteins and lipids play a key role in governing the organisation and coordination of intracellular biology. The frequent juxtaposition of proteinaceous biomolecular condensates to cellular membranes raises the intriguing prospect that phase transitions in proteins and lipids could be co-regulated. Here we investigate this possibility in the ribonucleoprotein (RNP) granule-ANXA11-lysosome ensemble, where ANXA11 tethers RNP granule condensates to lysosomal membranes to enable their co-trafficking. We show that changes to the protein phase state within this system, driven by the low complexity ANXA11 N-terminus, induce a coupled phase state change in the lipids of the underlying membrane. We identify the ANXA11 interacting proteins ALG2 and CALC as potent regulators of ANXA11-based phase coupling and demonstrate their influence on the nanomechanical properties of the ANXA11-lysosome ensemble and its capacity to engage RNP granules. The phenomenon of protein-lipid phase coupling we observe within this system offers an important template to understand the numerous other examples across the cell whereby biomolecular condensates closely juxtapose cell membranes.

Transcriptomic analysis of the effects of the HPV18 E6E7 gene on the cell death mode in esophageal squamous cell carcinoma.

Human papillomavirus (HPV) infection is one of the main causes of esophageal carcinoma (ESCA), and its carcinogenic mechanisms in ESCA require further investigation. E6 and E7 are HPV oncogenes, and their genomic integration is a crucial reason for the transformation of host cells into cancer cells. In order to reveal the role of oncogenes E6 and E7 in ESCA cells, the RNA-Seq raw data for HPV18-positive and -negative esophageal squamous cell carcinoma (ESCC) samples derived from the NCBI BioProject database were analyzed, and the differentially expressed genes were identified. Moreover, differentially expressed genes were enriched significantly in multiple cell death pathways, including apoptosis (cyclin-dependent kinase inhibitor 2A, plakophilin 1 and desmoglein 3), pyroptosis (gasdermin A, gasdermin C, NLR family pyrin domain containing 3, absent in melanoma 2, NLR family pyrin domain containing 1 and Toll like receptor 1) and autophagy (Unc-51 like autophagy activating kinase 1, adrenoceptor beta 2). Consequently, the effects of cisplatin-induced apoptosis and Hank's balanced salt solution-induced autophagy, and α-ketoglutarate-induced pyroptosis in the ESCC-expressing E6 and E7 cells were verified. Therefore, the expression of E6E7 may culminate in the inhibition of multiple cell death modes, which may also be one of the mechanisms of oncogene-induced carcinogenesis.

Sacubitril/valsartan alleviates sepsis-induced acute lung injury via inhibiting GSDMD-dependent macrophage pyroptosis in mice.

Sepsis-induced acute lung injury (ALI) is a life-threatening disorder with intricate pathogenesis. Macrophage pyroptosis reportedly plays a vital role in ALI. Although it has been established that angiotensin receptor blockers (ARBs) can reduce sepsis-induced organ injury, the efficacy of sacubitril/valsartan (SV) for sepsis has been largely understudied. Here, we aimed to investigate the role of SV in sepsis-induced ALI. Caecal ligation and puncture (CLP) were used to induce polymicrobial sepsis and related ALI. The therapeutic effects of SV in CLP mice were subsequently assessed. Gasdermin D (GSDMD)-/- mice were used to validate the signalling pathways affected by SV. In vitro, mouse bone marrow-derived macrophages (BMDMs) and Raw264.7 cells were treated with SV following exposure to lipopolysaccharide and adenosine triphosphate. Finally, the serum obtained from 42 septic patients was used for biochemical analysis. Compared to the other ARBs, SV yielded more pronounced anti-inflammatory effects on macrophages. In vivo, SV decreased mortality rates, significantly reduced lung damage and prevented the inflammatory response in CLP mice. In addition, SV suppressed GSDMD-mediated macrophage pyroptosis in mice. In BMDMs and Raw264.7 cells, the anti-inflammatory and anti-pyroptosis properties of SV were verified. SV treatment effectively inhibited NLRP3 inflammasome activation and prevented macrophage pyroptosis in a GSDMD-dependent manner. Furthermore, we found that septic individuals had considerably higher serum angiotensin II levels. Overall, we found that SV might prevent ALI in CLP mice by inhibiting GSDMD-mediated pyroptosis of macrophages. Thus, SV might be a viable drug for sepsis-induced ALI.