Machine Learning Screening and Validation of PANoptosis-Related Gene Signatures in Sepsis.

Background: Sepsis is a syndrome marked by life-threatening organ dysfunction and a disrupted host immune response to infection. PANoptosis is a recent conceptual development, which emphasises the interconnectedness among multiple programmed cell deaths in various diseases. Nevertheless, the role of PANoptosis in sepsis is still unclear. Methods: We utilized the GSE65682 dataset to identify PANoptosis-related genes (PRGs) and associated immune characteristics in sepsis, classified sepsis samples based on PRGs using the ConsensusClusterPlus method and applied the Weighted Gene Co-Expression Network Analysis (WGCNA) algorithm to identify cluster-specific hub genes. Based on PANoptosis -specific DEGs, we compared results from machine learning models and the best-performing model was selected. Predictive efficiency was validated through external dataset, nomogram, survival analysis, quantitative real-time PCR, and western blot. Results: The expression levels of PRGs were generally dysregulated in sepsis patients compared with normal samples, and higher PRGs expression correlated with increased immune cell infiltration. In addition, two distinct PANoptosis-related clusters were defined, and functional analysis indicated that DEGs associated with these clusters were primarily linked to immune-related pathways. The SVM model was selected as best-performing model, with lower residuals and the highest area under the curve (AUC = 0.967), which was then validated in an external dataset (AUC = 0.989) and through in vivo experiments. Additional validation through nomogram and survival analysis further confirmed its substantial predictive efficacy. Conclusion: Our findings exposed the intricate association between PANoptosis and sepsis, offering important insights on sepsis diagnosis and potential therapeutic targets.

Correction: UHPLC-MS/MS combined with microdialysis for simultaneous determination of nicotine and neurotransmitter metabolites in the rat hippocampal brain region: application to pharmacokinetic and pharmacodynamic study.

Correction for 'UHPLC-MS/MS combined with microdialysis for simultaneous determination of nicotine and neurotransmitter metabolites in the rat hippocampal brain region: application to pharmacokinetic and pharmacodynamic study' by Mingyu Zhu et al., Anal. Methods, 2024, https://doi.org/10.1039/d4ay00522h.

UHPLC-MS/MS combined with microdialysis for simultaneous determination of nicotine and neurotransmitter metabolites in the rat hippocampal brain region: application to pharmacokinetic and pharmacodynamic study.

Nicotine crosses the blood-brain barrier and interacts with nicotinic acetylcholine receptors, initiating a cascade of neurotransmitter effects with potential therapeutic implications for neurodegenerative conditions such as Alzheimer's and Parkinson's disease. The hippocampus, pivotal for cognitive processes, plays a crucial role in nicotine-mediated cognitive enhancement due to its abundant expression of nicotinic acetylcholine receptors, particularly the α7 subtype, which is heavily implicated in hippocampus-related behavioral functions and dysfunctions. However, the intricate process of nicotine metabolism within the hippocampus remains poorly understood, impeding our comprehension of how nicotine and its metabolites modulate neurotransmitter dynamics. To address this gap, we have developed and validated a novel methodology combining microdialysis with UHPLC-MS/MS, enabling simultaneous detection of 12 neurotransmitters, nicotine, and its seven metabolites within the rat hippocampus. The linearity range of the targeted compounds is satisfactory (R2 > 0.9970), with intra-day and inter-day precision not exceeding 12.7%, and accuracy ranging from -12.4% to 13.7%. Our findings reveal differential pharmacokinetics of nicotine and its metabolites in the α7KO group compared to the control group, characterized by heightened nicotine absorption and slower elimination and distribution in the former. Notably, the pharmacokinetic parameters of cotinine exhibit similarity across both groups. Studies investigating the impact of nicotine on monoamine neurotransmitters have elucidated its capacity to augment the release of dopamine, serotonin, norepinephrine, glutamate, and acetylcholine in the rat hippocampus. This integrated approach facilitates a comprehensive analysis of neurotransmitter alterations within the hippocampal region following nicotine administration, thereby providing robust technical support and scientific rationale for understanding the neurochemical effects of nicotine and its metabolites. Further exploration into the pharmacokinetics and pharmacodynamics of nicotine holds promise for uncovering novel therapeutic avenues in the management of neurodegenerative diseases such as Alzheimer's.

Cuproptosis-related Gene Signatures and Immunological Characterization in Sepsis-associated Acute Lung Injury.

BACKGROUND: Sepsis is a frequent cause of acute lung injury (ALI), characterized by immune dysregulation and a high mortality rate. The role of cuproptosis, a recently discovered cell death mechanism, in sepsis-associated ALI is still unclear. The study aimed to investigate the regulatory mechanisms and immune characteristics associated with cuproptosis in sepsisassociated ALI, with implications for novel diagnostic and therapeutic approaches. METHODS: Data from the GEO database was utilized to conduct a comprehensive analysis of the cuproptosis-related genes (CRGs) in sepsis-associated ALI. Gene enrichment analysis, WGCNA, CIBERSORT algorithm, and consensus clustering were employed to investigate the associations between CRGs and immune cells. A predictive model for sepsis-associated ALI was developed based on key CRGs, and its diagnostic accuracy was assessed. Finally, qPCR was employed to validate alterations in the expression of CRGs in the sepsis-associated ALI cellular model. RESULTS: A total of 14 CRGs were identified in sepsis-associated ALI. Strong correlations between the CRGs and immune cells were observed, and two different CRG subtypes were identified. The expression of immune-related factors in both the CRG and gene clusters exhibited similarities, suggesting a connection between the subgroups and immune cells. The prediction model effectively forecasted the incidence of sepsis-associated ALI based on the expression of CRGs. Finally, qPCR analysis confirmed that the expressions of CRGs in the sepsis-associated ALI cell model closely matched those identified through bioinformatic analyses. CONCLUSION: The study comprehensively evaluated the complex relationship between cuproptosis and sepsis-associated ALI. CRGs were found to be significantly associated with the occurrence, immune characteristics, and biological processes of sepsis-associated ALI. These findings provide valuable new insights into the mechanisms underlying sepsis-associated ALI.

Antitumor immunity and prognosis value elicited by FAT3 and LRP1B co-mutation in endometrial cancer.

OBJECTIVE: FAT3 and LRP1B are two tumor suppressor genes with high mutation frequency in multiple cancer types, we sought to investigate the prognostic and immunological significance of these two genes in EC. METHODS: Based on a cohort of 502 EC samples, we conducted a comprehensive analysis of its multidimensional data types including genomic, transcriptomic, and clinical information, the potential impact of FAT3 and LRP1B co-mutation on antitumor immune response and prognosis were systematically discussed. RESULTS: We observed that FAT3 and LRP1B co-mutation was not only defined a dataset with prominently increased TMB, decreased tumor aneuploidy, and specially enriched in MSI-H subtype, but also manifested increased expression of immune-related markers, especially exclusive upregulation of PD-L1 levels and higher PD-L1+/CD8A+ proportion. Further analysis focused on lymphocyte infiltration and pathway enrichment explored the immune cell composition of the microenvironment and underlying molecular mechanisms affecting tumor development. Furthermore, EC patients with FAT3 and LRP1B co-mutation possessed significantly prolonged PFS and OS, and the co-mutation status was proved to be an independent prognostic factor. And a nomogram with high predictive performance was constructed by incorporating co-mutation with clinical features. More strikingly, the prognosis of MSI-H patients in EC with co-mutation was significantly improved, and their survival reached a level consistent with the POLE subtype. CONCLUSIONS: In endometrial cancer, co-mutation of FAT3 and LRP1B not only leads to activation of the immune state, but also represents a subgroup with an improved prognosis, particularly in the MSI-H subtype.

[Investigation on the recommended dose of prebiotic in health food in China in 1996-2022].

OBJECTIVE: To understand the recommended dose distribution of prebiotic-containing health food in China. METHODS: The overall recommended dose of prebiotic health food was available from the label information of approved prebiotic health food from 1996 to 2022; the recommended dose distribution of prebiotic-containing health food was analyzed from different healthy functions and different ways of addition. RESULTS: There were 174 prebiotic-containing health food products with clear dose information, respectively, involving 5 prebiotics including Fructooligosaccharides, Galactooligosaccharides, Isomaltooligosaccharides, Xylo-oligosaccharides and Polydextrose, and the majority of prebiotics were added in combination, with 159 products. The recommended dose range of prebiotic-containing health food products was wide, and in general, the dose of prebiotic-containing health food products used alone was higher than the dose used in combination. The recommended daily intake range of health food containing Fructooligosaccharides was 5.28-17 500 mg/d, the recommended daily intake range of health food containing Isomaltooligosaccharides was 220-28 000 mg/d, the dose range of health food containing Xylo-oligosaccharides was 8.4-2 800 mg/d, the dose range of health food containing Polydextrose was 4-12 120 mg/d, the number of Galacto-Oligosaccharides products Only two kinds of products were included, with doses of 259.8 mg/d and 3500 mg/d, respectively. The claimed functions of prebiotic health food products were focused on laxative function, immunity enhancement, and regulation of intestinal flora. The application dose of prebiotic health food with different functional compounding additions was close to the overall dose. CONCLUSION: The recommended dosage range of prebiotics in health food containing prebiotics in China is large, and prebiotics in products are mainly added by compounding.

A high-dose of ursodeoxycholic acid treatment alleviates liver inflammation by remodeling gut microbiota and bile acid profile in a mouse model of non-alcoholic steatohepatitis.

Ursodeoxycholic acid (UDCA) is a hydrophilic bile acid commonly used for treating cholestatic liver disease. However, its efficacy on non-alcoholic steatohepatitis (NASH) was controversial. This study aimed to investigate the impact of a high dosage of UDCA on a mouse model of NASH. Forty 6-week-old mice were fed a high-fat high-cholesterol (HFHC) diet for 12 weeks to establish a mouse model of NASH, and then divided into four groups: two groups transitioned to a normal diet, and the other two groups maintained the HFHC diet. Each group was administered a daily dosage of 300 mg/kg of UDCA or saline for a period of 8 weeks. The 16 s ribosomal RNA genes extracted from mice fecal pellets were sequenced using next-generation sequencing techniques. Serum bile acid profiles were quantified using liquid chromatography electrospray ionization tandem mass spectrometry method. The results showed that UDCA treatment ameliorated liver inflammation, without affecting liver fibrosis. UDCA treatment reduced the relative abundance of the genera Bacteroides, Parabacteroides, and Intestinimonas, whereas increased the relative abundance of the genera norank_f_Muribaculaceae and Parasutterella in the HFHC-maintaining groups. The serum levels of total bile acids and total primary bile acids increased, whereas those of endogenous primary bile acids decreased after UDCA treatment. Correlation analysis showed that primary bile acids were negatively correlated with the genera norank_f_Christensenellaceae and unclassified_f_Ruminococcaceae. In conclusion, a high dosage of UDCA can alleviate liver inflammation, probably by modifying the composition of gut microbiota and serum bile acid profiles in NASH mice.

Characterization of the gut microbiota and fecal and blood metabolomes under various factors in urban children from Northwest China.

Introduction: Children have regional dynamics in the gut microbiota development trajectory. Hitherto, the features and influencing factors of the gut microbiota and fecal and plasma metabolites in children from Northwest China remain unclear. Methods: Shotgun metagenomic sequencing and untargeted metabolomics were performed on 100 healthy volunteers aged 2-12 years. Results: Age, body mass index (BMI), regular physical exercise (RPE), and delivery mode (DM) significantly affect gut microbiota and metabolites. Lactobacillus, Butyricimonas, Prevotella, Alistipes, and predicted pathway propanoate production were significantly increased with age while Bifidobacterium breve, B. animalis, B. pseudocatenulatum, Streptococcus infantis, and carbohydrate degradation were decreased. Fecal metabolome revealed that the metabolism of caffeine, amino acids, and lipid significantly increased with age while galactose metabolism decreased. Noticeably, BMI was positively associated with pathogens including Erysipelatoclostridium ramosum, Parabacteroides distasonis, Ruminococcus gnavus, and amino acid metabolism but negatively associated with beneficial Akkermansia muciniphila, Alistipes finegoldii, Eubacterium ramulus, and caffeine metabolism. RPE has increased probiotic Faecalibacterium prausnitzii and Anaerostipes hadrus, acetate and lactate production, and major nutrient metabolism in gut and plasma, but decreased pathobiont Bilophila wadsworthia, taurine degradation, and pentose phosphate pathway. Interestingly, DM affects the gut microbiota and metabolites throughout the whole childhood. Bifidobacterium animalis, Lactobacillus mucosae, L. ruminis, primary bile acid, and neomycin biosynthesis were enriched in eutocia, while anti-inflammatory Anaerofustis stercorihominis, Agathobaculum butyriciproducens, Collinsella intestinalis, and pathogenic Streptococcus salivarius, Catabacter hongkongensis, and amino acid metabolism were enriched in Cesarean section children. Discussion: Our results provided theoretical and data foundation for the gut microbiota and metabolites in preadolescent children's growth and development in Northwest China.

Identification of HK3 as a promising immunomodulatory and prognostic target in sepsis-induced acute lung injury.

BACKGROUND: Sepsis is a life-threatening global disease with a significant impact on human health. Acute lung injury (ALI) has been identified as one of the primary causes of mortality in septic patients. This study aimed to identify candidate genes involved in sepsis-induced ALI through a comprehensive approach combining bioinformatics analysis and experimental validation. METHODS: The datasets GSE65682 and GSE32707 obtained from the Gene Expression Omnibus database were merged to screen for sepsis-induced ALI related differentially expressed genes (DEGs). Functional enrichment and immune infiltration analyses were conducted on DGEs, with the construction of protein-protein interaction (PPI) networks to identify hub genes. In vitro and in vivo models of sepsis-induced ALI were used to study the expression and function of hexokinase 3 (HK3) using various techniques including Western blot, real-time PCR, immunohistochemistry, immunofluorescence, Cell Counting Kit-8, Enzyme-linked immunosorbent assay, and flow cytometry. RESULTS: The results of bioinformatics analysis have identified HK3, MMP9, and S100A8 as hub genes with diagnostic and prognostic significance for sepsis-induced ALI. The HK3 has profound effects on sepsis-induced ALI and exhibits a correlation with immune regulation. Experimental results showed increased HK3 expression in lung tissue of septic mice, particularly in bronchial and alveolar epithelial cells. In vitro studies demonstrated upregulation of HK3 in lipopolysaccharide (LPS)-stimulated lung epithelial cells, with cytoplasmic localization around the nucleus. Interestingly, following the knockdown of HK3 expression, lung epithelial cells exhibited a significant decrease in proliferation activity and glycolytic flux, accompanied by an increase in cellular inflammatory response, oxidative stress, and cell apoptosis. CONCLUSIONS: It was observed for the first time that HK3 plays a crucial role in the progression of sepsis-induced ALI and may be a valuable target for immunomodulation and therapy.Bioinformatics analysis identified HK3, MMP9, and S100A8 as hub genes with diagnostic and prognostic relevance in sepsis-induced ALI. Experimental findings showed increased HK3 expression in the lung tissue of septic mice, particularly in bronchial and alveolar epithelial cells. In vitro experiments demonstrated increased HK3 levels in lung epithelial cells stimulated with LPS, with cytoplasmic localization near the nucleus. Knockdown of HK3 expression resulted in decreased proliferation activity and glycolytic flux, increased inflammatory response, oxidative stress, and cell apoptosis in lung epithelial cells.

Utilizing a novel model of PANoptosis-related genes for enhanced prognosis and immune status prediction in kidney renal clear cell carcinoma.

Kidney renal clear cell carcinoma (KIRC) is the most common histopathologic type of renal cell carcinoma. PANoptosis, a cell death pathway that involves an interplay between pyroptosis, apoptosis and necroptosis, is associated with cancer immunity and development. However, the prognostic significance of PANoptosis in KIRC remains unclear. RNA-sequencing expression and mutational profiles from 532 KIRC samples and 72 normal samples with sufficient clinical data were retrieved from the Cancer Genome Atlas (TCGA) database. A prognostic model was constructed using differentially expressed genes (DEGs) related to PANoptosis in the TCGA cohort and was validated in a Gene Expression Omnibus (GEO) cohorts. Incorporating various clinical features, the risk model remained an independent prognostic factor in multivariate analysis, and it demonstrated superior performance compared to unsupervised clustering of the 21 PANoptosis-related genes alone. Further mutational analysis showed fewer VHL and more BAP1 alterations in the high-risk group, with alterations in both genes also associated with patient prognosis. The high-risk group was characterized by an unfavorable immune microenvironment, marked by reduced levels of CD4 + T cells and natural killer cells, but increased M2 macrophages and regulatory T cells. Finally, the risk model was predictive of response to immune checkpoint blockade, as well as sensitivity to sunitinib and paclitaxel. The PANoptosis-related risk model developed in this study enables accurate prognostic prediction in KIRC patients. Its associations with the tumor immune microenvironment and drug efficacy may offer potential therapeutic targets and inform clinical decisions.

Video snapshot compressive imaging using adaptive progressive coding for high-quality reconstruction under different illumination circumstances.

We consider capturing high-speed color video under different illumination conditions using a video snapshot compressive imaging system (video SCI). An adaptive progressive coding method is proposed, and we conduct an integrated design of the imaging system in terms of optics, mechanics, and control. Compared to previous video SCI systems, this adaptive progressive coding method mitigates the image stability issues in various illumination conditions, ensuring high-quality imaging while greatly improving the light throughput of the system. Based on the analysis of both simulation and real experimental results, we found that this imaging system can achieve color video shooting under an illumination range of 2 lux to 60 lux.

IL-4 and IL-13 induce equivalent expression of traditional M2 markers and modulation of reactive oxygen species in human macrophages.

In cardiovascular disease, pathological and protective roles are reported for the Th2 cytokines IL-4 and IL-13, respectively. We hypothesised that differential effects on macrophage function are responsible. Type I and II receptor subunit (IL-2Rγ, IL-4Rα and IL-13Rα1) and M2 marker (MRC-1, CCL18, CCL22) expression was assessed via RT-qPCR in IL-4- and IL-13-treated human primary macrophages. Downstream signalling was evaluated via STAT1, STAT3 and STAT6 inhibitors, and IL-4- and IL-13-induced reactive oxygen species (ROS) generation assessed. IL-4 and IL-13 exhibited equivalent potency and efficacy for M2 marker induction, which was attenuated by STAT3 inhibition. Both cytokines enhanced PDBu-stimulated superoxide generation however this effect was 17% greater with IL-4 treatment. Type I IL-4 receptor expression was increased on M1-like macrophages but did not lead to a differing ability of these cytokines to modulate M1-like macrophage superoxide production. Overall, this study did not identify major differences in the ability of IL-4 and IL-13 to modulate macrophage function, suggesting that the opposing roles of these cytokines in cardiovascular disease are likely to be via actions on other cell types. Future studies should directly compare IL-4 and IL-13 in vivo to more thoroughly investigate the therapeutic validity of selective targeting of these cytokines.

Multiomics Revealed the Multi-Dimensional Effects of Late Sleep on Gut Microbiota and Metabolites in Children in Northwest China.

Background Sleep plays a pivotal role in children's mental and physical development and has been linked to the gut microbiota in animals and adults. However, the characteristics of the gut microbiota and metabolites and the relationship to late bedtimes in children remain unclear. Methods In total, 88 eligible children, aged from 3 to 8 years, were recruited and divided into two groups according to the bedtime collected by designed questionnaires (early, before 22:00: n = 48; late, after 22:00, n = 40). Stools and plasma samples were collected to examine the characteristics of the gut microbiota and metabolites by shotgun metagenomics and metabolomics. Results The richness and diversity of the gut microbiota in children with early bedtime were significantly increased compared with the late ones. Coprococcus, Collinsella, Akkermansia muciniphila, and Bifidobacterium adolescentis were significantly more abundant in children with early bedtime, while Bacteroides and Clostridium sp. CAG-253 were obviously enriched in the late ones. A total of 106 metabolic pathways, including biosynthesis of ribonucleotide, peptidoglycan, and amino acids, and starch degradation were enriched in children with early bedtime, while 42 pathways were abundant in those with late bedtime. Notably, more gut microbial metabolites were observed in children with late bedtime, which included aldehyde, ketones, esters, amino acids and their metabolites, benzene and substituted derivatives, bile acids, heterocyclic compounds, nucleotide and metabolites, organic acid and derivatives, sugars and acyl carnitine. In plasma, fatty amides, lipids, amino acids, metabolites, hormones, and related compounds were enriched in children with early bedtime, while bile acids were higher in children with late bedtime. Association studies revealed that the different microbial species were correlated with metabolites from gut microbiota and plasma. Conclusions The results of our study revealed that the gut microbiota diversity and richness, and metabolic pathways were significantly extensive in children with early bedtime, whereas the gut microbial metabolites were significantly decreased, which might be related to gut microbial differences.

Factors associated with discordance in the assessment of fibrosis stage between transient elastography and liver biopsy in NAFLD patients.

BACKGROUND AND AIMS: Few studies focus on the concordance of fibrosis stage assessment between transient elastography (TE) and liver biopsy (LB) in non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the rate of discordance and factors associated with discordance in the fibrosis stage assessment between TE and LB. METHODS: LB-proven NAFLD patients were enrolled retrospectively. Liver fibrosis was assessed via TE and LB based on Steatosis-Activity-Fibrosis (SAF) criteria. Cohen's kappa was used to estimate the discordance between the fibrosis stage assessment by TE and LB. Logistic regression was utilized to determine the factors associated with discordance. RESULTS: A total of 172 eligible patients were included. The concordance of fibrosis staging between TE and LB was moderate (kappa = 0.446, p < 0.001). The overall rate of discordance was 52.90% (91/172) and highest in the F2 stage (66.28%) and F3 stage (60.42%), moderate in the F1 stage (23.81%), and lowest in the F4 stage (0.00%). The rate of overestimation and underestimation was 23.66% and 38.71% in patients detected by M-probe, while the rate of overestimation and underestimation was 33.87% and 19.35% in patients detected by XL-probe, respectively. BMI [OR=1.494, p = 0.017] and type 2 diabetes mellitus (T2DM) (OR=4.678, p = 0.008) were significantly associated with the overestimation in fibrosis stage assessment when the M-probe was applied. CONCLUSIONS: The discordance between TE and LB in fibrosis stage assessment was unexpectedly high and mainly observed in F1-F3 patients. BMI and T2DM were the factors associated with overestimation using the M-probe.

[Comparative study on the essential composition content of commercial follow-up formula for older infant with the requirements in the new national food safety standard in China from 2017 to 2022].

OBJECTIVE: To understand the distribution of the content range of essential ingredients in commercial follow-up formula for older infants in China, analyze the differences between the content of essential ingredients in commercial older infant formula milk powder in China and the requirements of the new national standard(GB 10766-2021). METHODS: The label information of 478 commercial follow-up formula for older infant registered and approved from January 2017 to June 2022 were collected and entered. The distribution of essential ingredients was statistically analyzed, which was compared with the requirements of the new national food safety standard. RESULTS: The new national standard has 31 essential components. Compared with the old national standard(GB 10767-2010), five indicators of carbohydrate, α-linolenic acid, choline, selenium and manganese were added. The new national standard has 28 essential component requirements revised, including 13 adjusted the lower limit, 7 adjusted the upper limit, and 16 essential components added the upper limit. Among the approved 478 older infant formula milk powders, the distribution of 11 essential ingredients were all in line with the new national standard, and 14 essential ingredients were less than the lower limit of the new national standard. The essential ingredients whose minimum value was less than the lower limit of the new national standard and the proportion exceeds 50% were vitamin D, iodine and choline. with the proportions(number of cases) of 98.33%(470 cases), 74.06%(354 cases) and 72.37%(275 cases), respectively. The maximum value of essential ingredients exceeded the maximum requirements stipulated in the new national standard, and the protein in 13.18%(63 cases) of the older infant formula milk powder was higher than the maximum requirements of the new national standard. CONCLUSION: The content of essential components in most commercial products in China meets the new national standard requirements. Some essential ingredients need to be adjusted.

Impact of heart failure on outcomes in patients with sepsis: A systematic review and meta-analysis.

BACKGROUND: Heart failure (HF) often affects the progress of sepsis patients, although its impact on outcomes is inconsistent and inconclusive. AIM: To conduct a systematic review and meta-analysis of the impact of HF on mortality in patients with sepsis. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library databases were searched to compare the outcomes of sepsis patients with HF. A random effect model was used to summarize the mortality data, and the odds ratio (OR) and 95% confidence interval (CI) were calculated as effect indicators. RESULTS: Among 18001 records retrieved in the literature search, 35712 patients from 10 separate studies were included. The results showed that sepsis patients with HF were associated with increased total mortality (OR = 1.80, 95%CI: 1.34-2.43; I2 = 92.1%), with high heterogeneity between studies. Significant subgroup differences according to age, geographical location, and HF patient sample were observed. HF did not increase the 1-year mortality of patients (OR = 1.11, 95%CI: 0.75-1.62; I2 = 93.2%), and the mortality of patients with isolated right ventricular dysfunction (OR=2.32, 95%CI: 1.29-4.14; I2 = 91.5%) increased significantly. CONCLUSION: In patients with sepsis, HF is often associated with adverse outcomes and mortality. Our results call for more high-quality research and strategies to improve outcomes for sepsis patients with HF.

Hybrid Multi-Dimensional Attention U-Net for Hyperspectral Snapshot Compressive Imaging Reconstruction.

In order to capture the spatial-spectral (x,y,λ) information of the scene, various techniques have been proposed. Different from the widely used scanning-based methods, spectral snapshot compressive imaging (SCI) utilizes the idea of compressive sensing to compressively capture the 3D spatial-spectral data-cube in a single-shot 2D measurement and thus it is efficient, enjoying the advantages of high-speed and low bandwidth. However, the reconstruction process, i.e., to retrieve the 3D cube from the 2D measurement, is an ill-posed problem and it is challenging to reconstruct high quality images. Previous works usually use 2D convolutions and preliminary attention to address this challenge. However, these networks and attention do not exactly extract spectral features. On the other hand, 3D convolutions can extract more features in a 3D cube, but increase computational cost significantly. To balance this trade-off, in this paper, we propose a hybrid multi-dimensional attention U-Net (HMDAU-Net) to reconstruct hyperspectral images from the 2D measurement in an end-to-end manner. HMDAU-Net integrates 3D and 2D convolutions in an encoder-decoder structure to fully utilize the abundant spectral information of hyperspectral images with a trade-off between performance and computational cost. Furthermore, attention gates are employed to highlight salient features and suppress the noise carried by the skip connections. Our proposed HMDAU-Net achieves superior performance over previous state-of-the-art reconstruction algorithms.

Ionization induced by the ponderomotive force in intense and high-frequency laser fields.

Atomic stabilization is a universal phenomenon that occurs when atoms interact with intense and high-frequency laser fields. In this work, we systematically study the influence of the ponderomotive (PM) force, present around the laser focus, on atomic stabilization. We show that the PM force could induce tunneling and even over-barrier ionization to the otherwise stabilized atoms. Such effect may overweigh the typical multiphoton ionization under moderate laser intensities. Our work highlights the importance of an improved treatment of atomic stabilization that includes the influence of the PM force.

Inhibition of TANK-binding kinase1 attenuates the astrocyte-mediated neuroinflammatory response through YAP signaling after spinal cord injury.

AIMS: TANK-binding kinase 1 (TBK1) is involved in regulating the pathological process of a variety of inflammatory diseases in the central nervous system. However, its role and underlying molecular mechanisms in spinal cord injury (SCI) remain largely unknown. METHODS: We employed the TBK1 inhibitor amlexanox (ALX) to address this question. An in vivo clip-compressive SCI model and in vitro lipopolysaccharide (LPS)-induced astrocyte inflammation model were established to examine the effects of TBK1 inhibition on the expression of proinflammatory cytokines. RESULTS: In this study, we found that TBK1 and TBK1-medicated innate immune pathways, such as TBK1/IRF3 and noncanonical NF-κB signaling, were activated in astrocytes and neurons after SCI. Furthermore, inhibition of TBK1 by ALX alleviated neuroinflammation response, reduced the loss of motor neurons, and improved the functional recovery after SCI. Mechanistically, inhibition of TBK1 activity promoted the activation of the noncanonical NF-κB signaling pathway and inhibited p-IRF3 activity in LPS-induced astrocytes, and the TBK1 activity was required for astrocytic activation through yes-associated protein (YAP) signaling after SCI and in LPS-induced astrocytes inflammation model. CONCLUSION: TBK1-medicated innate immune pathway in astrocytes through YAP signaling plays an important role in the pathogenesis of SCI and inhibition of TBK1 may be a potential therapeutic drug for SCI.

Ultra-broadband dual-polarization and arbitrary ratio power splitters based on Bezier curve optimized multimode interference.

We propose and demonstrate two types of 1 × 2 power splitters based on multimode interference (MMI), which are ultra-compact, fabrication friendly, and low loss. The contours of MMI and output tapers are optimized with Bezier curves, which can implement arbitrary ratio power splitters (ARPSs) and ultra-broadband dual-polarization power splitters (UDPSs). For ARPSs, the experimental results show that arbitrary power splitting ratios can be obtained with an average excess loss (EL) of 0.17 dB at 1550 nm for fundamental TE polarization. For UDPSs, the experimental results show that the ELs for fundamental TE and TM polarization are less than 0.63 dB and 0.44 dB over a large bandwidth of 415 nm (1260-1675 nm). The footprints of the proposed devices are less than 10 µm × 2.5 µm (without input straight waveguide) with large fabrication tolerance.