Systematic comparison of sequencing-based spatial transcriptomic methods.

Recent developments of sequencing-based spatial transcriptomics (sST) have catalyzed important advancements by facilitating transcriptome-scale spatial gene expression measurement. Despite this progress, efforts to comprehensively benchmark different platforms are currently lacking. The extant variability across technologies and datasets poses challenges in formulating standardized evaluation metrics. In this study, we established a collection of reference tissues and regions characterized by well-defined histological architectures, and used them to generate data to compare 11 sST methods. We highlighted molecular diffusion as a variable parameter across different methods and tissues, significantly affecting the effective resolutions. Furthermore, we observed that spatial transcriptomic data demonstrate unique attributes beyond merely adding a spatial axis to single-cell data, including an enhanced ability to capture patterned rare cell states along with specific markers, albeit being influenced by multiple factors including sequencing depth and resolution. Our study assists biologists in sST platform selection, and helps foster a consensus on evaluation standards and establish a framework for future benchmarking efforts that can be used as a gold standard for the development and benchmarking of computational tools for spatial transcriptomic analysis.

Establishment of diagnostic model and identification of diagnostic markers between liver cancer and cirrhosis based on multi-chip and machine learning.

OBJECTIVE: Most cases of hepatocellular carcinoma (HCC) arise as a consequence of cirrhosis. In this study, our objective is to construct a comprehensive diagnostic model that investigates the diagnostic markers distinguishing between cirrhosis and HCC. METHODS: Based on multiple GEO datasets containing cirrhosis and HCC samples, we used lasso regression, random forest (RF)-recursive feature elimination (RFE) and receiver operator characteristic analysis to screen for characteristic genes. Subsequently, we integrated these genes into a multivariable logistic regression model and validated the linear prediction scores in both training and validation cohorts. The ssGSEA algorithm was used to estimate the fraction of infiltrating immune cells in the samples. Finally, molecular typing for patients with cirrhosis was performed using the CCP algorithm. RESULTS: The study identified 137 differentially expressed genes (DEGs) and selected five significant genes (CXCL14, CAP2, FCN2, CCBE1 and UBE2C) to construct a diagnostic model. In both the training and validation cohorts, the model exhibited an area under the curve (AUC) greater than 0.9 and a kappa value of approximately 0.9. Additionally, the calibration curve demonstrated excellent concordance between observed and predicted incidence rates. Comparatively, HCC displayed overall downregulation of infiltrating immune cells compared to cirrhosis. Notably, CCBE1 showed strong correlations with the tumour immune microenvironment as well as genes associated with cell death and cellular ageing processes. Furthermore, cirrhosis subtypes with high linear predictive scores were enriched in multiple cancer-related pathways. CONCLUSION: In conclusion, we successfully identified diagnostic markers distinguishing between cirrhosis and hepatocellular carcinoma and developed a novel diagnostic model for discriminating the two conditions. CCBE1 might exert a pivotal role in regulating the tumour microenvironment, cell death and senescence.

Extracellular vesicles from apoptotic BMSCs ameliorate osteoporosis via transporting regenerative signals.

Rationale: Mesenchymal stromal cells (MSCs) are considered a promising resource for cell therapy, exhibiting efficacy in ameliorating diverse bone diseases. However, most MSCs undergo apoptosis shortly after transplantation and produce apoptotic extracellular vesicles (ApoEVs). This study aims to clarify the potential role of ApoEVs from apoptotic MSCs in ameliorating osteoporosis and molecular mechanism. Methods: In this study, Dio-labeled bone marrow mesenchymal stem cells (BMSCs) were injected into mice to track BMSCs apoptosis and ApoEVs production. ApoEVs were isolated from BMSCs after inducing apoptosis, the morphology, size distribution, marker proteins expression of ApoEVs were characterized. Protein mass spectrometry analysis revealed functional differences in proteins between ApoEVs and BMSCs. BMSCs were adopted to test the cellular response to ApoEVs. Ovariectomy mice were used to further compare the ability of ApoEVs in promoting bone formation. SiRNA and lentivirus were used for gain and loss-of-function assay. Results: The results showed that BMSCs underwent apoptosis within 2 days after being injected into mice and produce a substantial quantity of ApoEVs. Proteomic analysis revealed that ApoEVs carried a diverse functional array of proteins, and easily traversed the circulation to reach the bone. After being phagocytized by endogenous BMSCs, ApoEVs efficiently promoted the proliferation, migration, and osteogenic differentiation of BMSCs. In an osteoporosis mouse model, treatment of ApoEVs alleviated bone loss and promoted bone formation. Mechanistically, ApoEVs carried Ras protein and activated the Ras/Raf1/Mek/Erk pathway to promote osteogenesis and bone formation in vitro and in vivo. Conclusion: Given that BMSC-derived ApoEVs are high-yield and easily obtained, our data underscore the substantive role of ApoEVs from dying BMSCs to treat bone loss, presenting broad implications for cell-free therapeutic modalities.

Study on pharmacokinetics and tissue distribution of deoxypodophyllotoxin and its metabolites in tumour-bearing mice.

To study the pharmacokinetics of deoxypodophyllotoxin and its metabolites in non-small cell lung cancer (NSCLC) bearing mice.Using the established LC-MS/MS method for simultaneous determination of deoxypodophyllotoxin and its three main metabolites (M1, M2 and M7) in biological samples, the concentrations of deoxypodophyllotoxin and its metabolites in plasma, tumour and major tissues of tumour-bearing mice were investigated after 6.25 and 25 mg/kg intravenous administration of deoxypodophyllotoxin.The exposure results of drug concentration showed that after intravenous injection of 6.25 and 25 mg/kg of DPT into tumour-bearing mice, the AUC ratio of DPT in tumour tissue to DPT in plasma was 4.23 and 3.80, respectively. While, the AUC ratio of metabolite M2 in tumour tissue to M2 in plasma was 0.82 and 0.76, respectively.Deoxypodophyllotoxin had higher affinity with tumour tissues than plasma, while its metabolite M2 had less affinity with tumour tissues than deoxypodophyllotoxin, but the exposure level of M2 in plasma was higher than that of deoxypodophyllotoxin. Deoxypodophyllotoxin was widely distributed in tumour-bearing mice. After intravenous injection of 25 mg/kg deoxypodophyllotoxin, the concentration of deoxypodophyllotoxin in other tissues except liver and muscle was relatively high, especially in lung, fat and reproductive organs.

Systemic oxidative stress levels during the course of pregnancy: Associations with exposure to air pollutants.

Increased systemic oxidative stress, implicated in adverse pregnancy outcomes for both mothers and fetuses, has been associated with gestational exposure to air pollutants such as polycyclic aromatic hydrocarbons (PAHs), fine particulate matter (PM2.5), and nitrogen dioxide (NO2). However, it is unclear whether exposure to pollutants at levels below the current air quality standards can increase oxidative stress in pregnant women. In a cohort of 305 pregnant persons residing in western New York, we examined the association between exposure to PM2.5, NO2, and PAHs (measured as urinary 1-hydroxypyrene) and urinary biomarkers of oxidative stress (malondialdehyde [MDA] and 8-hydroxy-2'-deoxyguanosine [8-OHdG]) measured in each trimester. After controlling for gestational stage, maternal age, lifestyles, and socioeconomic factors, each interquartile range (IQR) increase in 1-hydroxypyrene concentration (65.8 pg/ml) was associated with a 7.73% (95%CI: 3.18%,12.3%) higher in MDA levels throughout the pregnancy and in the first and second trimester. An IQR increase in PM2.5 concentration (3.20 µg/m3) was associated with increased MDA levels in the first trimester (8.19%, 95%CI: 0.28%,16.1%), but not the 2nd (-7.99%, 95% CI: 13.8%, -2.23%) or 3rd trimester (-2.81%, 95% CI: 10.0%, 4.38%). The average cumulative PM2.5 exposures in the 3-7 days before urine collection were associated with increased 8-OHdG levels during the second trimester, with the largest difference (22.6%; 95% CI: 3.46%, 41.7%) observed in relation to a one IQR increase in PM2.5 concentration in the previous 7 days. In contrast, neither oxidative stress biomarker was associated with NO2 exposure. Observed in pregnant women exposed to low-level air pollution, these findings expanded previously reported associations between systemic oxidative stress and high-level PM2.5 and PAH concentrations. Further, the first and second trimesters may be a susceptible window during pregnancy for oxidative stress responses to air pollution exposure.

Identification and validation of key genes in gastric cancer: insights from in silico analysis, clinical samples, and functional assays.

INTRODUCTION: The underlying mechanisms of gastric cancer (GC) remain unknown. Therefore, in this study, we employed a comprehensive approach, combining computational and experimental methods, to identify potential key genes and unveil the underlying pathogenesis and prognosis of GC. METHODS: Gene expression profiles from GEO databases (GSE118916, GSE79973, and GSE29272) were analyzed to identify DEGs between GC and normal tissues. A PPI network was constructed using STRING and Cytoscape, followed by hub gene identification with CytoHubba. Investigations included expression and promoter methylation analysis, survival modeling, mutational and miRNA analysis, gene enrichment, drug prediction, and in vitro assays for cellular behaviors. RESULTS: A total of 83 DEGs were identified in the three datasets, comprising 41 up-regulated genes and 42 down-regulated genes. Utilizing the degree and MCC methods, we identified four hub genes that were hypomethylated and up-regulated: COL1A1, COL1A2, COL3A1, and FN1. Subsequent validation of their expression and promoter methylation on clinical GC samples through targeted bisulfite sequencing and RT-qPCR analysis further confirmed the hypomethylation and overexpression of these genes in local GC patients. Furthermore, it was observed that these hub genes regulate tumor proliferation and metastasis in in vivo and exhibited mutations in GC patients. CONCLUSION: We found four potential diagnostic and prognostic biomarkers, including COL1A1, COL1A2, COL3A1, and FN1 that may be involved in the occurrence and progression of GC.

Long-term kidney outcomes in patients with permanent hypoparathyroidism after total thyroidectomy for benign disease: A population-based study.

BACKGROUND: Permanent hypoparathyroidism is a significant complication after total thyroidectomy. This study aimed to evaluate the long-term impact of postoperative permanent hypoparathyroidism on kidney outcomes. METHODS: Data of patients undergoing total thyroidectomy from 1999 to 2014 were retrieved. The estimated glomerular filtration rate was determined from serum creatinine results. Permanent hypoparathyroidism was defined as requiring oral calcium and vitamin D supplements postoperatively for at least 6 months. The primary outcome was a sustained decline in the estimated glomerular filtration rate from baseline by ≥50%. Secondary outcomes were end-stage kidney disease (a composite of sustained estimated glomerular filtration rate <15 mL/min/1.73 m2, need for dialysis, and kidney transplantation) and rate of estimated glomerular filtration rate decline. Patients with and without permanent hypoparathyroidism were compared. Multivariable Cox regression analysis was performed to identify independent risk factors for sustained estimated glomerular filtration rate decline by ≥50%. RESULTS: In total, 3,245 patients were eligible for analysis; 418 patients (12.9%) had permanent hypoparathyroidism. Upon median follow-up of 11.6 years, more patients with permanent hypoparathyroidism had a sustained decline in estimated glomerular filtration rate from baseline by ≥50% compared to those without (15.6% vs 6.9%, P < .001). Similar findings were obtained on Kaplan-Meier analysis (P < .001). Permanent hypoparathyroidism was an independent risk factor for sustained estimated glomerular filtration rate decline by ≥50% (adjusted hazard ratio 2.77, P < .001). Other risk factors included age, preoperative estimated glomerular filtration rate <60 mL/min/1.73m2, and diabetes mellitus. Patients with permanent hypoparathyroidism had a more rapid estimated glomerular filtration rate decline (-1.60 vs -0.70 mL/min/1.73 m2/year, difference -0.91 mL/min/1.73m2/year, P < .001). CONCLUSION: Patients with postsurgical permanent hypoparathyroidism were at greater risk of renal impairment. Further research is warranted to improve the identification and preservation of parathyroid glands during thyroidectomy to minimize patient morbidity.

Investigation on the Preparation and Performances of Epoxy-Modified Asphalt Binder and Its Mixtures.

Epoxy-modified asphalt binder has been widely used in steel deck pavement due to its excellent properties and it is a potential candidate for long life pavements. However, its short reserve time limits its widespread application in pavement engineering. Therefore, this work developed a novel epoxy-modified asphalt binder composed of a laboratory-made curing agent as a solution. Firstly, optimization of preparation temperature of this new material was studied to balance the requirements of enough construction time and the material strength and elongation. The epoxy-modified asphalt binder, prepared at the optimal temperature of 140 °C, had a reserve time exceeding 120 min, whereas the tensile strength and the elongation at failure were 2.22 MPa and 216%, respectively, which satisfied the standard requirements of paving epoxy material well. Secondly, the asphalt mixture property tests demonstrate excellent high-temperature rutting resistance, water stability and low-temperature anti-cracking ability. Additionally, the compatibility and colloidal stability of this epoxy-modified asphalt binder were analyzed in terms of microphase structure. The uniform microphase distribution of this binder showed by the laser confocal microscope observation in both short-term aging case and long-term aging case, indicates the great compatibility between asphalt and epoxy resin during paving process and service life. Furthermore, fatigue tests were conducted to evaluate the long-term durability. The fatigue life of epoxy-modified asphalt mixtures increased by 435%, 427%, 342%, and 276% under the stress ratios of 0.3, 0.4, 0.5, and 0.6, respectively, compared to those of SBS-modified asphalt mixtures. All these results indicate that the new epoxy-modified asphalt material is promising for applications in pavement engineering, especially suitable for long-life road pavement.

Survey of Advanced Nonlinear Control Strategies for UAVs: Integration of Sensors and Hybrid Techniques.

This survey paper explores advanced nonlinear control strategies for Unmanned Aerial Vehicles (UAVs), including systems such as the Twin Rotor MIMO system (TRMS) and quadrotors. UAVs, with their high nonlinearity and significant coupling effects, serve as crucial benchmarks for testing control algorithms. Integration of sophisticated sensors enhances UAV versatility, making traditional linear control techniques less effective. Advanced nonlinear strategies, including sensor-based adaptive controls and AI, are increasingly essential. Recent years have seen the development of diverse sliding surface-based, sensor-driven, and hybrid control strategies for UAVs, offering superior performance over linear methods. This paper reviews the significance of these strategies, emphasizing their role in addressing UAV complexities and outlining future research directions.

Release of perfluoroalkyl acids from sediments under the effects of the discharge ratio and flow flux at a Y-shaped confluence.

The sediments in riverine environments contain notably high concentrations of perfluoroalkyl acids (PFAAs), which may be released into the water body under different hydrodynamic forces, such as those occurring at Y-shaped confluences. The release of PFAAs may pose a significant risk to the surrounding aquatic ecosystems. However, our understanding of the release and transport of PFAAs from sediments at Y-shaped confluences remains unclear. Thus, in this study, we performed a series of flume experiments to explore the effects of discharge ratio and total flow flux on the release and redistribution of PFAAs. The results indicated that these two parameters significantly affected the hydrodynamic features of confluences and the water physicochemical parameters. PFAA concentrations in the dissolved phase and suspended particulate matter (SPM) rose significantly as the discharge ratio and total flow flux increased. The dissolved phase was the predominant loading form of PFAAs, with short-chain PFAAs being the main kind, while long-chain PFAAs were dominant in the SPM. The spatial distribution pattern of PFAAs in sediments at the confluence exhibited a high degree of correspondence with hydrodynamic zones. The separation zone and maximum velocity zone were consistent with sediment regions with low and high capacities to release PFAAs, respectively. The patterns of variation in PFAA distribution were comparable to those observed in hydrodynamic zones as the discharge ratio and total flow flux varied. Furthermore, these two parameters altered the partitioning behaviors of PFAAs; specifically, the PFAAs in sediments tended to be released into the pore-water, while the liberated PFAAs tended to attach to SPM. Linear regression and correlation analyses suggested that the stream-wise and vertical flow velocity components near the sediment-water interface were the primary contributors to sediment suspension and PFAA exchange between the water column and pore-water. These findings will help us to understand the patterns of PFAA release in sediments at Y-shaped confluences and assist in the management of PFAA-contaminated sediments at these locations.

Thermoelectric Performance of Tetrahedrite (Cu12Sb4S13) Thin Films: The Influence of the Substrate and Interlayer.

In the present work, tetrahedrite Cu12Sb4S13 thin films were deposited on various substrates via aerosol-assisted chemical vapor deposition (AACVD) using diethyldithiocarbamate complexes as precursors. A buffer layer of Sb2O3 with a small lattice mismatch to Cu12Sb4S13 was applied to one of the glass substrates to improve the quality of the deposited thin film. The buffer layer increased the coverage of the Cu12Sb4S13 thin film, resulting in improved electrical transport properties. The growth of the Cu12Sb4S13 thin films on the other substrates, including ITO-coated glass, a SiO2-coated Si wafer, and mica, was also investigated. Compared to the films grown on the other substrates, the Cu12Sb4S13 thin film deposited on the SiO2-coated Si wafer showed a dense and compact microstructure and a larger grain size (qualities that are beneficial for carrier transport), yielding a champion power factor (PF) of ∼362 µW cm-1 K-2 at 625 K. The choice of substrate strongly influenced the composition, microstructure, and electrical transport properties of the deposited Cu12Sb4S13 thin film. At 460 K, the highest zT value that was obtained for the thin films was ∼0.18. This is comparable to values reported for Cu-Sb-S bulk materials at the same temperature. Cu12Sb4S13 thin films deposited using AACVD are promising for thermoelectric applications. To the best of our knowledge, the first full thermoelectric characterization of the Cu12Sb4S13 thin film is performed in this work.

Laser-induced shock wave two-dimensional extraction technology based on a beam deflection method.

This paper introduces a method for analyzing the spatiotemporal progression of laser-induced shock waves using the beam deflection technique. This method allows for the accurate measurement of the shock wave evolution and can replace high-speed cameras. The results demonstrate the detection signals at various distances and energies, as well as the extraction and reconstruction of the shock wave velocities and propagation trajectories. The characteristic velocities of the shock waves propagating in air from various metals and energetic materials were measured and compared with the results obtained from high-speed cameras. The study also predicts the macroscopic detonation velocity of energetic materials based on the characteristic velocity. Overall, this approach offers a reliable and cost-effective method for studying the shock waves and has potential applications in various fields.

Molecular ferroelectric with low-magnetic-field magnetoelectricity at room temperature.

Magnetoelectric materials, which encompass coupled magnetic and electric polarizabilities within a single phase, hold great promises for magnetic controlled electronic components or electric-field controlled spintronics. However, the realization of ideal magnetoelectric materials remains tough due to the inborn competion between ferroelectricity and magnetism in both levels of symmetry and electronic structure. Herein, we introduce a methodology for constructing single phase paramagnetic ferroelectric molecule [TMCM][FeCl4], which shows low-magnetic-field magnetoelectricity at room temperature. By applying a low magnetic field (≤1 kOe), the halogen Cl‧‧‧Cl distance and the volume of [FeCl4]- anions could be manipulated. This structural change causes a characteristic magnetostriction hysteresis, resulting in a substantial deformation of ~10-4 along the a-axis under an in-plane magnetic field of 2 kOe. The magnetostrictive effect is further qualitatively simulated by density functional theory calculations. Furthermore, this mechanical deformation significantly dampens the ferroelectric polarization by directly influencing the overall dipole configuration. As a result, it induces a remarkable α31 component (~89 mV Oe-1 cm-1) of the magnetoelectric tensor. And the magnetoelectric coupling, characterized by the change of polarization, reaches ~12% under 40 kOe magnetic field. Our results exemplify a design methodology that enables the creation of room-temperature magnetoelectrics by leveraging the potent effects of magnetostriction.

Intense Turbulent Bursts Promote the Release of Perfluoroalkyl Acids from Sediments at High Flow Velocity.

Despite frequent detection of high levels of perfluoroalkyl acids (PFAAs) in sediments, research on the environmental fate of PFAAs in sediments, particularly under hydrodynamic conditions, is rather limited, challenging effective management of PFAA loadings. Therefore, this study investigated the release and transport of 15 PFAAs in sediments under environmentally relevant flow velocities using recirculating flumes and revealed the underlying release mechanisms by identifying related momentum transfer. An increased velocity enhanced the release magnitude of total PFAAs by a factor of 3.09. The release capacity of short-chain PFAAs was notably higher than that of long-chain PFAAs, and this pattern was further amplified by flow velocity. Pore-water drainage was the major pathway for PFAA release, with the release amount predominantly determined by flow velocity-induced release intensity and depth, as well as affected by the perfluorocarbon chain length and sediment size. The weak anion exchanger-diffusion gradients in the thin-film technique confirmed that the release depth of PFAAs increased with flow velocity. Quadrant analysis revealed that the rise in the frequency and intensity of turbulent bursts driven by sweeps and ejections at high flow velocity was the underlying cause of the increased release magnitude and depth of PFAAs.

Citric Acid: A Nexus Between Cellular Mechanisms and Biomaterial Innovations.

Citrate-based biodegradable polymers have emerged as a distinctive biomaterial platform with tremendous potential for diverse medical applications. By harnessing their versatile chemistry, these polymers exhibit a wide range of material and bioactive properties, enabling them to regulate cell metabolism and stem cell differentiation through energy metabolism, metabonegenesis, angiogenesis, and immunomodulation. Moreover, the recent US Food and Drug Administration (FDA) clearance of the biodegradable poly(octamethylene citrate) (POC)/hydroxyapatite-based orthopedic fixation devices represents a translational research milestone for biomaterial science. POC joins a short list of biodegradable synthetic polymers that have ever been authorized by the FDA for use in humans. The clinical success of POC has sparked enthusiasm and accelerated the development of next-generation citrate-based biomaterials. This review presents a comprehensive, forward-thinking discussion on the pivotal role of citrate chemistry and metabolism in various tissue regeneration and on the development of functional citrate-based metabotissugenic biomaterials for regenerative engineering applications.

Research on the influencing factors of Chinese agricultural brand competitiveness based on DEMATEL-ISM.

Agricultural products are pivotal to the national economy, and a comprehensive analysis of brand competitiveness significantly contributes to the support of agricultural structural adjustment and modernization. Focusing on the Yangtze River Delta region of China, this study develops an evaluation index system encompassing four dimensions: core brand competitiveness, brand management, market competitiveness, and innovation in branding. Utilizing a DEMATEL-ISM model, this research elucidates the intrinsic relationships among factors that influence brand competitiveness, resulting in a four-tier hierarchical model. The analysis delineates key factors at superficial, intermediate, and profound levels that influence brand competitiveness. Notably, regional production bases, along with innovations in brand technology and systems, emerge as profound influencers. Drawing on these findings, the study recommends strategies to enhance production foundations, accurately define development trajectories, spearhead technological innovation to foster collective reform efforts, and advocate for institutional advancements to bolster healthy brand growth.

Targeting gut microbiota for immunotherapy of diseases.

With advances in next-generation sequencing technology, there is growing evidence that the gut microbiome plays a key role in the host's innate and adaptive immune system. Gut microbes and their metabolites directly or indirectly regulate host immune cells. Crucially, dysregulation of the gut microbiota is often associated with many immune system diseases. In turn, microbes modulate disease immunotherapy. Data from preclinical to clinical studies suggest that the gut microbiota may influence the effectiveness of tumor immunotherapy, particularly immune checkpoint inhibitors (ICIs). In addition, the most critical issue now is a COVID-19 vaccine that generates strong and durable immunity. A growing number of clinical studies confirm the potential of gut microbes to enhance the efficacy of COVID-19 vaccines. However, it is still unclear how gut bacteria interact with immune cells and what treatments are based on gut microbes. Here, we outline recent advances in the effects and mechanisms of the gut microbiota and its metabolites (tryptophan metabolites, bile acids, short-chain fatty acids, and inosine) on different immune cells (dendritic cells, CD4+T cells, and macrophages). It also highlights innovative intervention strategies and clinical trials of microbiota-based checkpoint blocking therapies for tumor immunity, and ongoing efforts to maintain the long-term immunogenicity of COVID-19 vaccines. Finally, the challenges to be overcome in this area are discussed. These provide an important basis for further research and clinical translation of gut microbiota.

Blood microbial signatures associated with mortality in patients with sepsis: A pilot study.

Sepsis is a life-threatening illness caused by the dysregulated host response to infection. Nevertheless, our current knowledge of the microbial landscape in the blood of septic patients is still limited. Next-generation sequencing (NGS) is a sensitive method to quantitatively characterize microbiomes at various sites of the human body. In this study, we analyzed the blood microbial DNA of 22 adult patients with sepsis and 3 healthy subjects. The presence of non-human DNA was identified in both healthy and septic subjects. Septic patients had a markedly altered microbial DNA profile compared to healthy subjects over α- and ß-diversity. Unexpectedly, the patients could be further divided into two subgroups (C1 and C2) based on ß-diversity analysis. C1 patients showed much higher bacteria, viruses, fungi, and archaea abundance, and a higher level of α-diversity (Chao1, Observed and Shannon index) than both C2 patients and healthy subjects. The most striking difference was seen in the case of Streptomyces violaceusniger, Phenylobacterium sp. HYN0004, Caulobacter flavus, Streptomyces sp. 11-1-2, and Phenylobacterium zucineum, the abundance of which was the highest in the C1 group. Notably, C1 patients had a significantly poorer outcome than C2 patients. Moreover, by analyzing the patterns of microbe-microbe interactions in healthy and septic subjects, we revealed that C1 and C2 patients exhibited distinct co-occurrence and co-exclusion relationships. Together, our study uncovered two distinct microbial signatures in the blood of septic patients. Compositional and ecological analysis of blood microbial DNA may thus be useful in predicting mortality of septic patients.

Peroxiredoxin II exerts neuroprotective effects by inhibiting endoplasmic reticulum stress and oxidative stress-induced neuronal pyroptosis.

BACKGROUND: Intracerebral hemorrhage (ICH) is a critical neurological condition with few treatment options, where secondary immune responses and specific cell death forms, like pyroptosis, worsen brain damage. Pyroptosis involves gasdermin-mediated membrane pores, increasing inflammation and neural harm, with the NLRP3/Caspase-1/GSDMD pathway being central to this process. Peroxiredoxin II (Prx II), recognized for its mitochondrial protection and reactive oxygen species (ROS) scavenging abilities, appears as a promising neuronal pyroptosis modulator. However, its exact role and action mechanisms need clearer definition. This research aims to explore Prx II impact on neuronal pyroptosis and elucidate its mechanisms, especially regarding endoplasmic reticulum (ER) stress and oxidative stress-induced neuronal damage modulation. METHODS AND RESULTS: Utilizing MTT assays, Microscopy, Hoechst/PI staining, Western blotting, and immunofluorescence, we found Prx II effectively reduces LPS/ATP-induced pyroptosis and neuroinflammation in HT22 hippocampal neuronal cells. Our results indicate Prx II's neuroprotective actions are mediated through PI3K/AKT activation and ER stress pathway inhibition, diminishing mitochondrial dysfunction and decreasing neuronal pyroptosis through the ROS/MAPK/NF-κB pathway. These findings highlight Prx II potential therapeutic value in improving intracerebral hemorrhage outcomes by lessening secondary brain injury via critical signaling pathway modulation involved in neuronal pyroptosis. CONCLUSIONS: Our study not only underlines Prx II importance in neuroprotection but also opens new therapeutic intervention avenues in intracerebral hemorrhage, stressing the complex interplay between redox regulation, ER stress, and mitochondrial dynamics in neuroinflammation and cell death management.