Multi-site sulfonation of lignin for the synthesis of a high-performance dye dispersant.

Sulfonated lignin-based dye dispersants have intensively attracted attention due to their low cost, renewability and abundant sources. However, their utilization is limited by the low content of sulfonic groups and high content of hydroxyl groups in their complex lignin structure, which results in various problems such as high reducing rate of dye, severe staining of the fibers and uneven dyeing. Here, the multi-site sulfonated lignin-based dispersants were prepared with high sulfonic group content (2.20 mmol/g) and low hydroxyl content (2.43 mmol/g). When using it as the dispersant, the dye uptake rate was improved from 69.23 % to 98.55 %, the reducing rate was decreased from 20.82 % to 2.03 %, the K/S value was reduced from 0.69 to 0.02, and the particle sizes in dye system before and after high temperature treatment were stabilized below 0.5 µm. Besides, the dispersion effect was significantly improved because no obvious separation between dye and water was observed even if without the assistance of grinding process. In short, the multi-site sulfonation method proposed in this work could remarkably improve the performances of the lignin-based dye dispersants, which would facilitate the development of the dye dispersion and the high value utilization of lignin.

A functionalized glass fiber as the adsorbent for efficient analysis of endocrine disruptors in aqueous environments.

Estrogens and bisphenols are typical endocrine disruptors (EDs) that pose a potential hazard to the human body due to their widespread presence in aqueous environments. In this study, a ß-cyclodextrin porous crosslinked polymer (ß-CD-PCP) was prepared in-situ on a glass fiber surface by a nucleophilic substitution reaction. An effective and sensitive solid phase microextraction method using functionalized glass fiber with ß-CD-PCP coating as the adsorbent was established for the detection of 11 EDs in a water environment. The ß-CD-PCP was in-situ prepared on a glass fiber surface by a nucleophilic substitution reaction. The ß-CD-PCP successfully separated five estrogens (ESTs) and six bisphenols (BPs) through hydrophobic and π-π interactions. The conditions affecting extraction were optimized. Under the optimized conditions, the ESTs obtained a high enrichment effect (1795-2328), low limits of detection (0.047 µg L-1) and a good linearity range (0.2-15.0 µg L-1). Furthermore, the spiked recoveries of analyte ESTs in aqueous environments were between 82.9-115.7 %. The results indicated that the prepared functionalized glass fibers exhibited good adsorption properties, and the established analytical method was reliable for monitoring trace ESTs and BPs in aqueous environments.

Effects of beta-blockers use on mortality of patients with acute respiratory distress syndrome: a retrospective cohort study.

Introduction: Acute respiratory distress syndrome (ARDS) remains a challenging disease with limited prevention and treatment options. The usage of beta-blockers may have potential benefits in different critical illnesses. This study aimed to investigate the correlation between beta-blocker therapy and mortality in patients with ARDS. Materials and methods: This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care (MIMIC) IV database and focused on patients diagnosed with ARDS. The primary outcome of the study was 30-day mortality. To account for confounding factors, a multivariable analysis was performed. Propensity score matching (PSM) was carried out on a 1:1 ratio. Robust assessments were conducted using inverse probability weighting (IPTW), standardized mortality ratio weighting (SMRW), pairwise algorithms (PA), and overlap weights (OW). Results: A total of 1,104 patients with ARDS were included in the study. Univariate and multivariate Cox regression analyses found that the 30-day mortality for 489 patients (23.7%) who received beta-blockers was significantly lower than the mortality rate of 615 patients (35.9%) who did not receive beta-blockers. After adjusting for potential confounders through PSM and propensity score, as well as utilizing IPTW, SMRW, PA, and OW, the results remained robust, with the hazard ratios (HR) ranging from 0.42 to 0.58 and all p-values < 0.001. Evaluation of the E-values indicated the robustness of the results even in the presence of unmeasured confounding. Conclusion: The findings suggest a potential association between beta-blocker usage and reduced mortality in critically ill patients with ARDS. However, further validation of this observation is needed through randomized controlled trials.

Single-nucleus multi-omic profiling of human placental syncytiotrophoblasts identifies cellular trajectories during pregnancy.

The human placenta has a vital role in ensuring a successful pregnancy. Despite the growing body of knowledge about its cellular compositions and functions, there has been limited research on the heterogeneity of the billions of nuclei within the syncytiotrophoblast (STB), a multinucleated entity primarily responsible for placental function. Here we conducted integrated single-nucleus RNA sequencing and single-nucleus ATAC sequencing analyses of human placentas from early and late pregnancy. Our findings demonstrate the dynamic heterogeneity and developmental trajectories of STB nuclei and their correspondence with human trophoblast stem cell (hTSC)-derived STB. Furthermore, we identified transcription factors associated with diverse STB nuclear lineages through their gene regulatory networks and experimentally confirmed their function in hTSC and trophoblast organoid-derived STBs. Together, our data provide insights into the heterogeneity of human STB and represent a valuable resource for interpreting associated pregnancy complications.

DNA N6-methyladenine methylase N6AMT1 controls neuropathic pain through epigenetically modifying Kcnj16 in dorsal horn neurons.

ABSTRACT: Nerve injury-induced aberrant changes in gene expression in spinal dorsal horn neurons are critical for the genesis of neuropathic pain. N6-methyladenine (m 6 A) modification of DNA represents an additional layer of gene regulation. Here, we report that peripheral nerve injury significantly decreased the level of m 6 A-specific DNA methyltransferase 1 ( N6amt1 ) in dorsal horn neurons. This decrease was attributed, at least partly, to a reduction in transcription factor Nr2f6 . Rescuing the decrease in N6amt1 reversed the loss of m 6 A at the promoter for inwardly rectifying potassium channel subfamily J member 16 ( Kcnj16 ), mitigating the nerve injury-induced upregulation of Kcnj16 expression in the dorsal horn and alleviating neuropathic pain hypersensitivities. Conversely, mimicking the downregulation of N6amt1 in naive mice erased DNA m 6 A at the Kcnj16 promoter, elevated Kcnj16 expression, and led to neuropathic pain-like behaviors. Therefore, decreased N6amt1 caused by NR2F6 is required for neuropathic pain, likely through its regulation of m 6 A-controlled KCNJ16 in dorsal horn neurons, suggesting that DNA m 6 A modification may be a potential new target for analgesic and treatment strategies.

Spinal-Specific Super Enhancer in Neuropathic Pain.

Dysfunctional gene expression in nociceptive pathways plays a critical role in the development and maintenance of neuropathic pain. Super enhancers (SEs), composed of a large cluster of transcriptional enhancers, are emerging as new players in the regulation of gene expression. However, whether SEs participate in nociceptive responses remains unknown. Here, we report a spinal-specific SE (SS-SE) that regulates chronic constriction injury (CCI)-induced neuropathic pain by driving Ntmt1 and Prrx2 transcription in dorsal horn neurons. Peripheral nerve injury significantly enhanced the activity of SS-SE and increased the expression of NTMT1 and PRRX2 in the dorsal horn of male mice in a bromodomain-containing protein 4 (BRD4)-dependent manner. Both intrathecal administration of a pharmacological BRD4 inhibitor JQ1 and CRISPR-Cas9-mediated SE deletion abolished the increased NTMT1 and PRRX2 in CCI mice and attenuated their nociceptive hypersensitivities. Furthermore, knocking down Ntmt1 or Prrx2 with siRNA suppressed the injury-induced elevation of phosphorylated extracellular-signal-regulated kinase (p-ERK) and glial fibrillary acidic protein (GFAP) expression in the dorsal horn and alleviated neuropathic pain behaviors. Mimicking the increase in spinal Ntmt1 or Prrx2 in naive mice increased p-ERK and GFAP expression and led to the genesis of neuropathic pain-like behavior. These results redefine our understanding of the regulation of pain-related genes and demonstrate that BRD4-driven increases in SS-SE activity is responsible for the genesis of neuropathic pain through the governance of NTMT1 and PRRX2 expression in dorsal horn neurons. Our findings highlight the therapeutic potential of BRD4 inhibitors for the treatment of neuropathic pain.SIGNIFICANCE STATEMENT SEs drive gene expression by recruiting master transcription factors, cofactors, and RNA polymerase, but their role in the development of neuropathic pain remains unknown. Here, we report that the activity of an SS-SE, located upstream of the genes Ntmt1 and Prrx2, was elevated in the dorsal horn of mice with neuropathic pain. SS-SE contributes to the genesis of neuropathic pain by driving expression of Ntmt1 and Prrx2 Both inhibition of SS-SE with a pharmacological BRD4 inhibitor and genetic deletion of SS-SE attenuated pain hypersensitivities. This study suggests an effective and novel therapeutic strategy for neuropathic pain.

Facile construction of lignin-based network composite hydrogel for efficient adsorption of methylene blue from wastewater.

Adsorption method is an effective approach to treat wastewater containing methylene blue. Herein, a cost-effective and eco-friendly lignin-based network composite hydrogel adsorbent (PAA@SML) was constructed by using polyacrylic acid (PAA) to crosslink with sulfomethylated lignin (SML) via free radical polymerization for adsorption of methylene blue (MB) from wastewater. The constructed PAA@SML-0.2 exhibited remarkable adsorption performance towards removal of MB, with a maximum theoretical adsorption capacity of 777.1 mg·g-1. The improved efficiency can be attributed to the well-established network structure and abundant hydrophilic functional groups present in the adsorbent, promoting the interaction between methylene blue (MB) molecules and the adsorption sites of the adsorbent. The adsorption process of the adsorbent for MB followed the pseudo-second-order kinetic and the Langmuir isotherm models, which illustrated the adsorption process attributed to monolayer chemisorption. Mechanism investigation confirmed that the adsorption of MB by PAA@SML-0.2 primarily relied on hydrogen bonding and electrostatic interactions. Moreover, the recyclability test demonstrated excellent regeneration usability and stability of PAA@SML-0.2, and the adsorption capacity maintained above 74.0 % after five cycles. This constructed lignin-based network composite hydrogel is considered to have great potential in the treatment of organic dye in wastewater.

Renewable galactomannan-based biogums with structure regulation to protect zinc metal anodes via blocking and confinement effect.

Galactomannan-based biogums were derived from fenugreek, guar, tara, and carob and consisted of mannose and galactose with different ratios, as well as the implementation of high-value utilization was very significant for sustainable development. In this work, renewable and low-cost galactomannan-based biogums were designed and developed as functional coatings protected on the Zn metal anodes. The molecule structure of galactomannan-based biogums were explored on the effect of anticorrosion ability and uniform deposition behavior through the introduction of fenugreek gum, guar gum, tara gum, and carob gum with different ratios of mannose to galactose as 1.2:1, 2:1, 3:1, and 4:1. The existence of biogum protective layers can reduce the contact area between Zn anodes and aqueous electrolyte to enhance the anticorrosion ability of Zn anodes. Rich oxygen-containing groups in galactomannan-based biogums can coordinate with Zn2+ and Zn atoms to form ion conductivity gel layer and adsorb closely on the surface of Zn metal, which can induce uniform deposition of Zn2+ to avoid dendrite growth. Zn electrodes protected by biogums can cycle impressively for 1980 h with 2 mA cm-2 and 2 mAh cm-2. This work can provide a novel strategy to enhance Zn metal anodes' electrochemical performance, as well as implement the high-value application of biomass-based biogums as functional coatings.

Unraveling the Lignin Structural Variation in Different Bamboo Species.

The structure of cellulolytic enzyme lignin (CEL) prepared from three bamboo species (Neosinocalamus affinis, Bambusa lapidea, and Dendrocalamus brandisii) has been characterized by different analytical methods. The chemical composition analysis revealed a higher lignin content, up to 32.6% of B. lapidea as compared to that of N. affinis (20.7%) and D. brandisii (23.8%). The results indicated that bamboo lignin was a p-hydroxyphenyl-guaiacyl-syringyl (H-G-S) lignin associated with p-coumarates and ferulates. Advanced NMR analyses displayed that the isolated CELs were extensively acylated at the γ-carbon of the lignin side chain (with either acetate and/or p-coumarate groups). Moreover, a predominance of S over G lignin moieties was found in CELs of N. affinis and B. lapidea, with the lowest S/G ratio observed in D. brandisii lignin. Catalytic hydrogenolysis of lignin demonstrated that 4-propyl-substituted syringol/guaiacol and propanol guaiacol/syringol derived from ß-O-4' moieties, and methyl coumarate/ferulate derived from hydroxycinnamic units were identified as the six major monomeric products. We anticipate that the insights of this work could shed light on the sufficient understanding of lignin, which could open a new avenue to facilitate the efficient utilization of bamboo.

C-DONN: compact diffractive optical neural network with deep learning regression.

A new method to improve the integration level of an on-chip diffractive optical neural network (DONN) is proposed based on a standard silicon-on-insulator (SOI) platform. The metaline, which represents a hidden layer in the integrated on-chip DONN, is composed of subwavelength silica slots, providing a large computation capacity. However, the physical propagation process of light in the subwavelength metalinses generally requires an approximate characterization using slot groups and extra length between adjacent layers, which limits further improvements of the integration of on-chip DONN. In this work, a deep mapping regression model (DMRM) is proposed to characterize the process of light propagation in the metalines. This method improves the integration level of on-chip DONN to over 60,000 and elimnates the need for approximate conditions. Based on this theory, a compact-DONN (C-DONN) is exploited and benchmarked on the Iris plants dataset to verify the performance, yielding a testing accuracy of 93.3%. This method provides a potential solution for future large-scale on-chip integration.

Identifying a dynamic transcriptomic landscape of the cynomolgus macaque placenta during pregnancy at single-cell resolution.

Supporting healthy pregnancy outcomes requires a comprehensive understanding of the cellular hierarchy and underlying molecular mechanisms in the primate placenta during gestation. Here, we present a single-cell transcriptome-wide view of the cynomolgus macaque placenta throughout gestation. Bioinformatics analyses and multiple validation experiments suggested that placental trophoblast cells exhibited stage-specific differences across gestation. Interactions between trophoblast cells and decidual cells also showed gestational stage-dependent differences. The trajectories of the villous core cells indicated that placental mesenchymal cells were derived from extraembryonic mesoderm (ExE.Meso) 1, whereas placental Hofbauer cells, erythrocytes, and endothelial cells were derived from ExE.Meso2. Comparative analyses of human and macaque placentas uncovered conserved features of placentation across species, and the discrepancies of extravillous trophoblast cells (EVTs) between human and macaque correlated to their differences in invasion patterns and maternal-fetal interactions. Our study provides a groundwork for elucidating the cellular basis of primate placentation.

Surface Control Behavior toward Crystal Regulation and Anticorrosion Capacity for Zinc Metal Anodes.

The commercial application of high-safety aqueous zinc (Zn) secondary batteries is hindered by the poor cycling life of Zn metal anodes. Here we propose a dendrite growth and hydrogen evolution corrosion reaction mechanism from the binding energy of the deposited crystal plane on the Zn surface and the adsorption energy of H2O molecules on different crystal planes as well as the binding energy of H2O molecules with Zn2+ ions. The biomass-based alkyl polyglucoside (APG) surfactant is adopted as an electrolyte additive of 0.15% to regulate the preferential growth of a parallel Zn(002) plane and enhance the anticorrosion ability of Zn metal anodes. The robust binding and adsorption energies of APG with Zn2+ ions in the aqueous electrolyte and the Zn(002) plane on Zn surface generate a synergistic effect to increase the concentration of Zn2+ ions on the APG-adsorbed Zn(002) plane, endowing the continuous growth of the preferential parallel Zn(002) plane and the excellent anticorrosion capacity. Accordingly, the long-term cycle stability of 4000 h can be achieved for Zn anodes with APG additives, which is better than that with pure ZnSO4 electrolyte. With the addition of APG in the anolyte electrolyte, Zn-I2 full cells display excellent cycling performance (70 mAh g-1 after 20000 cycles) as compared with that without APG additives.

Lignin-based composites with enhanced mechanical properties by acetone fractionation and epoxidation modification.

Epoxy resin is widely used in various fields of the national economy due to its excellent chemical and mechanical properties. Lignin is mainly derived from lignocelluloses as one of the most abundant renewable bioresources. Due to the diversity of lignin sources and the complexity as well as heterogeneity of its structure, the value of lignin has not been fully realized. Herein, we report the utilization of industrial alkali lignin for the preparation of low-carbon and environmentally friendly bio-based epoxy thermosetting materials. Specifically, epoxidized lignin with substituted petroleum-based chemical bisphenol A diglycidyl ether (BADGE) in various proportions was cross-linked to fabricate thermosetting epoxies. The cured thermosetting resin revealed enhanced tensile strength (4.6 MPa) and elongation (315.5%) in comparison with the common BADGE polymers. Overall, this work provides a practicable approach for lignin valorization toward tailored sustainable bioplastics in the context of a circular bioeconomy.

Designed synthesis of multifunctional lignin-based adsorbent for efficient heavy metal ions removal and electromagnetic wave absorption.

Multifunctional lignin-based adsorbents, which have shown great application prospect, have attracted widespread attention. Herein, a series of multifunctional lignin-based magnetic recyclable adsorbents were prepared from carboxymethylated lignin (CL), which was rich in carboxyl group (-COOH). After optimizing the mass ratio of CL to Fe3O4, the prepared CL/Fe3O4 (3:1) adsorbent showed efficient adsorption capacities for heavy metal ions. The kinetic and isotherm nonlinear fitting studies revealed that the adsorption process followed the second-order kinetic and Langmuir models, and the maximum adsorption capacities (Qmax) of CL/Fe3O4 (3:1) magnetic recyclable adsorbent for Pb2+, Cu2+ and Ni2+ ions reached 189.85, 124.43 and 106.97 mg/g, respectively. Meanwhile, after 6 cycles, the adsorption capacities of CL/Fe3O4 (3:1) for Pb2+, Cu2+ and Ni2+ ions could keep at 87.4 %, 83.4 % and 82.3 %, respectively. In addition, CL/Fe3O4 (3:1) also exhibited excellent electromagnetic wave absorption (EMWA) performance with a reflection loss (RL) of -28.65 dB at 6.96 GHz under the thickness of 4.5 mm, and its effective absorption bandwidth (EAB) achieved 2.24 GHz (6.08-8.32 GHz). In short, the prepared multifunctional CL/Fe3O4 (3:1) magnetic recyclable adsorbent with outstanding adsorption capacity for heavy metal ions and superior EMWA capability opens a new avenue for the diversified utilization of lignin and lignin-based adsorbent.

Valorization of lignin through reductive catalytic fractionation of fermented corn stover residues.

The fermented corn stover residues are abundant renewable lignin-rich bioresources that show great potential to produce aromatic phenols. However, selective catalytic hydrogenolysis of this residual material still remains challenge to obtain high yields. Herein, a novel strategy to produce monophenolic compounds from the fermented stover over a commercial Pd/C catalyst was proposed. Taking the reaction temperature as the key variable, the highest monomer yield was 28.5 wt% at 220 °C in compaction with that of the pristine corn stover (22.8 wt%). The enhanced monophenol yield was due to the higher contents of lignin and less recalcitrance in the fermented stover. Moreover, the van Krevelen diagram revealed a slight selective CO bond scission of lignin macromolecular during fermentation as well as the dehydration and deoxygenation in hydrogenolysis reaction. Overall, this work opens a new avenue for the valorization of lignin through reductive catalytic fractionation of agricultural wastes.

Effect of Guizhi Fuling Capsule on Apoptosis of Myeloma Cells Through Mitochondrial Apoptosis Pathway.

OBJECTIVE: To observe the effects of Guizhi Fuling Capsule (GZFLC) on myeloma cells and explore the mechanisms. METHODS: MM1S and RPMI 8226 cells were co-cultured with different concentrations of serum and the cell experiments were divided into negative (10%, 20% and 40%) groups, GZFLC (10%, 20%, and 40%) groups and a control group. Cell counting kit-8 (CCK-8) assays and flow cytometry were used to detect the viability and apoptosis levels of myeloma cells. The effects on mitochondria were examined by reactive oxygen specie (ROS) and tetrechloro-tetraethylbenzimidazol carbocyanine iodide (JC-1) assays. Western blot was used to detect the expression of B cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), cleaved caspase-3, -9, cytochrome C (Cytc) and apoptotic protease-activating factor 1 (Apaf-1). RPMI 8226 cells (2 × 107) were subcutaneously inoculated into 48 nude mice to study the in vivo antitumor effects of GZFLC. The mice were randomly divided into four groups using a completely randomized design, the high-, medium-, or low-dose GZFLC (840, 420, or 210 mg/kg per day, respectively) or an equal volume of distilled water, administered daily for 15 days. The tumor volume changes in and survival times of the mice in the GZFLC-administered groups and a control group were observed. Cytc and Apaf-1 expression levels were detected by immunohistochemistry. RESULTS: GZFLC drug serum decreased the viability and increased the apoptosis of myeloam cells (P<0.05). In addition, this drug increased the ROS levels and decreased the mitochondrial membrane potential (P<0.01). Western blot showed that the Bcl-2/Bax ratios were decreased in the GZFLC drug serum-treated groups, whereas the expression levels of cleaved caspase-3, -9, Cytc and Apaf-1 were increased (all P<0.01). Over time, the myeloma tumor volumes of the mice in the GZFLC-administered groups decreased, and survival time of the mice in the GZFLC-administered groups were longer than that of the mice in the control group. Immunohistochemical analysis of tumor tissues from the mice in the GZFLC-administered groups revealed that the Cytc and Apaf-1 expression levels were increased (P<0.05). CONCLUSION: GZFLC promoted apoptosis of myeloma cells through the mitochondrial apoptosis pathway and significantly reduced the tumor volumes in mice with myeloma, which prolonged the survival times of the mice.

[Platelet-rich plasma vs corticosteroid for treatment of rotator cuff tendinopathy:a Meta-analysis].

OBJECTIVE: To explore clinical effects regrarding functional recovery, pain relief, and range of motion of shoulder of platelet-rich plasma (PRP) injection and corticosteroid(CS) injection in treating rotator cuff tendinopathy. METHODS: Randomized controlled trials (RCT) of PRP injection and CS injection in Cochrane Library, EMBASE(Excerpta Medica Database), PebMed, China knowledge Network(CNKI) and Wanfang database were searched from building database to April 20, 2022. According to inclusion and exclusion criteria, literature screening, data extraction and quality evaluation were carried out between two independent researchers, and extracted data were statistically analyzed by Review Manager 5.4.1 software. Short-term (3-6 weeks), medium-term (8-12 weeks) and long-term (≥24 weeks) visual analogue score (VAS), American Shoulder and Elbow Surgeons (ASES) score, Xi'an Western Ontario Rotator Cuff Index (WORC) and shoulder range of motion (ROM) were compared between two groups. RESULTS: Totally 7 RCT were included with 379 patients, 188 patients in PRP group and 191 patients in CS group. Meta analysis results showed there were no significant difference in VAS, ASES and WORC between short-term group and medium-term group(P>0.05). During long-term follow-up, there were significant differences in ASES score[MD=7.1, 95%CI(2.06, 12.14), P=0.006] and VAS [MD=-1.55, 95%CI(-2.65, 0.55), P=0.002]. There was no significant difference in shoulder ROM between two groups(P>0.05). CONCLUSION: For patients with shoulder cuff tendon disease, there are no significant difference in pain relief and functional recovery during short and medium-term follow-up period. However, RPR injection showed advantages over corticosteroid injection in terms of functional recovery and pain relief during long-term follow-up. There is no significant difference in shoulder range of motion between two groups during the whole follow-up period.

The diversity of trophoblast cells and niches of placenta accreta spectrum disorders revealed by single-cell RNA sequencing.

Placenta accreta spectrum disorders (PAS) are severe pregnancy complications that occur when extravillous trophoblast cells (EVTs) invade beyond the uterine inner myometrium and are characterized by hypervascularity on prenatal ultrasound and catastrophic postpartum hemorrhage. The potential mechanisms remain incompletely understood. With single-cell RNA-sequencing analysis on the representative invasive parts and the normal part obtained from the same PAS placenta, we profiled the pathological landscape of invasive PAS placenta and deciphered an intensified differentiation pathway from progenitor cytotrophoblasts (CTBs) to EVTs via LAMB4 + and KRT6A + CTBs. In the absence of the decidua, the invasive trophoblasts of various differentiation states interacted with ADIRF + and DES + maternal stromal cells. The PAS-associated hypervascularity might be due to the enhanced crosstalk of trophoblasts, stromal cells and vascular endothelial cells. Finally, we presented an immune microenvironmental landscape of invasive PAS. The pathogenesis of PAS could be further explored with current resources for future targeted translational studies.

Prediction of 30-day mortality in heart failure patients with hypoxic hepatitis: Development and external validation of an interpretable machine learning model.

Background: This study aimed to explore the impact of hypoxic hepatitis (HH) on survival in heart failure (HF) patients and to develop an effective machine learning model to predict 30-day mortality risk in HF patients with HH. Methods: In the Medical Information Mart for Intensive Care (MIMIC)-III and IV databases, clinical data and survival situations of HF patients admitted to the intensive care unit (ICU) were retrospectively collected. Propensity Score Matching (PSM) analysis was used to balance baseline differences between HF patients with and without HH. Kaplan Meier analysis and multivariate Cox analysis were used to determining the effect of HH on the survival of CF patients. For developing a model that can predict 30-day mortality in CF patients with HH, the feature recurrence elimination (RFE) method was applied to feature selection, and seven machine learning algorithms were employed to model construction. After training and hyper-parameter optimization (HPO) of the model through cross-validation in the training set, a performance comparison was performed through internal and external validation. To interpret the optimal model, Shapley Additive Explanations (SHAP) were used along with the Local Interpretable Model-agnostic Explanations (LIME) and the Partial Dependence Plot (PDP) techniques. Results: The incidence of HH was 6.5% in HF patients in the MIMIC cohort. HF patients with HH had a 30-day mortality rate of 33% and a 1-year mortality rate of 51%, and HH was an independent risk factor for increased short-term and long-term mortality risk in HF patients. After RFE, 21 key features (21/56) were selected to build the model. Internal validation and external validation suggested that Categorical Boosting (Catboost) had a higher discriminatory capability than the other models (internal validation: AUC, 0.832; 95% CI, 0.819-0.845; external validation: AUC, 0.757 95% CI, 0.739-0.776), and the simplified Catboost model (S-Catboost) also had good performance in both internal validation and external validation (internal validation: AUC, 0.801; 95% CI, 0.787-0.813; external validation: AUC, 0.729, 95% CI, 0.711-0.745). Conclusion: HH was associated with increased mortality in HF patients. Machine learning methods had good performance in identifying the 30-day mortality risk of HF with HH. With interpretability techniques, the transparency of machine learning models has been enhanced to facilitate user understanding of the prediction results.

Development and validation of a predictive model for in-hospital mortality in patients with sepsis-associated liver injury.

Background: Sepsis is often accompanied by organ dysfunction and acute organ failure, among which the liver is commonly involved. Sepsis patients suffering from liver injury have a greater risk of mortality than patients suffering from general sepsis. As of now, there are no tools that are specifically designed for assessing the prognosis of such patients. This study aimed to develop and validate a model to predict the risk of in-hospital mortality in patients with sepsis-associated liver injury (SALI). Methods: Data were obtained from the Medical Information Mart for Intensive Care (MIMIC)-IV database. In the analysis, all patients with SALI who met the inclusion and exclusion criteria were included. A primary outcome was in-hospital mortality, and clinical data were extracted for these patients. In a ratio of 8:2, the data were divided into training and validation groups at random. Least absolute shrinkage and selection operator (LASSO) regression was used for data dimension reduction and feature selection, and independent factors related to prognosis were identified through multi-factor logistics analysis. A nomogram was developed to visualize the model, and the performance of the model was evaluated by the area under the curve (AUC) as well as calibration and decision curve analysis (DCA) through internal verification. Results: A total of 616 and 154 patients with SALI were included in the training and validation cohorts, respectively. The LASSO regression and logistic multivariate analysis showed that nine factors were associated with in-hospital mortality in patients with SALI. Both the training and validation cohorts had higher AUCs than sequential organ failure assessment (SOFA) and simplified acute physiology score 2 (SAPS2): 0.753 (95% CI: 0.715-0.791) and 0.783 (95% CI: 0.749-0.817), respectively. Both the training and validation cohorts showed good calibration results for the prediction model. In terms of clinical practicability, DCA of the predictive model demonstrated greater net benefits than the SOFA and SAPS2 scores. Conclusions: We developed a predictive model that can effectively predict the in-hospital mortality of SALI patients, with satisfactory performance and clinical practicability. This model can assist clinicians in the early identification of high-risk patients and provide a reference for clinical treatment strategies.