Relationship between the albumin-corrected anion gap and short-term prognosis among patients with cardiogenic shock: a retrospective analysis of the MIMIC-IV and eICU databases.

OBJECTIVES: We aimed to investigate the association between the albumin-corrected anion gap (ACAG) and the prognosis of cardiogenic shock (CS). DESIGN: A multicentre retrospective cohort study. SETTING: Data were collected from the Medical Information Mart for Intensive Care (MIMIC-IV) and eICU Collaborative Research Database (eICU-CRD) datasets. PARTICIPANTS: 808 and 700 individuals from the MIMIC-IV and eICU-CRD, respectively, who were diagnosed with CS. PRIMARY AND SECONDARY OUTCOMES: The primary endpoint was short-term all-cause mortality, including intensive care unit (ICU), in-hospital and 28-day mortality. The secondary endpoints were the 28-day free from the ICU duration and the length of ICU stay. RESULTS: CS patients were divided into two groups according to the admission ACAG value: the normal ACAG group (≤20 mmol/L) and the high ACAG group (> 20 mmol/L). CS patients with higher ACAG values exhibited increased short-term all-cause mortality rates, including ICU mortality (MIMIC-IV cohort: adjusted HR: 1.43, 95% CI=1.05-1.93, p=0.022; eICU-CRD cohort: adjusted HR: 1.38, 95% CI=1.02-1.86, p=0.036), in-hospital mortality (MIMIC-IV cohort: adjusted HR: 1.31, 95% CI=1.01-1.71, p=0.03; eICU-CRD cohort: adjusted HR: 1.47, 95% CI=1.12-1.94, p=0.006) and 28-day mortality (adjusted HR: 1.42, 95% CI: 1.11 to 1.83, p=0.007). A positive linear correlation was observed between the ACAG value and short-term mortality rates via restricted cubic splines. Compared with the AG, the ACAG presented a larger area under the curve for short-term mortality prediction. In addition, the duration of intensive care was longer, whereas the 28-day free from the ICU duration was shorter in patients with a higher ACAG value in both cohorts. CONCLUSION: The ACAG value was independently and strongly associated with the prognosis of patients with CS, indicating that the ACAG value is superior to the conventional AG value.

Unraveling the rapid progression of non-target lesions: risk factors and the therapeutic potential of PCSK9 inhibitors in post-PCI patients.

BACKGROUND: Rapid progression of non-target lesions (NTLs) leads to a high incidence of NTL related cardiac events post-PCI, which accounting half of the recurrent cardiac events. It is important to identify the risk factors and establish an accurate clinical prediction model for the rapid progression of NTLs post-PCI. PCSK9 inhibitors lower LDL-c levels significantly, also show the anti-inflammation effect, and may have the potential to reduce the rapid progression of NTLs post-PCI. We tried to test this hypothesis and explore the potential mechanisms. METHODS: This retrospective study included 1250 patients who underwent the first PCI and underwent repeat coronary angiography for recurrence of chest pain within 24 months. General characteristics, laboratory tests and inflammatory factors(IL-10, IL-6, IL-8, IL-1ß, sIL-2R, and TNF-α) were collected. Machine learning (LASSO regression) was mainly employed to select the important characteristic risk factors for the rapid progression of NTLs post-PCI and build prediction models. Finally, mediator analysis was employed to explore the potential mechanisms by which PCSK9 inhibitors reduce the rapid progression of NTLs post-PCI. RESULTS: There were more diabetes, less beta-blockers and PCSK9 inhibitors application, higher HbA1c, LDL-c, ApoB, TG, TC, uric acid, hs-CRP, TNF-α, IL-6, IL-8, and sIL-2R in NTL progressed group. LDL-c, hs-CRP, IL-8, and sIL-2R were characteristic risk factors for the rapid progression of NTLs post-PCI, combining LDL-c, hs-CRP, IL-8, and sIL-2R builds the optimal model for predicting the rapid progression of NTLs post-PCI (AUC = 0.632). LDL-c had a clear and incomplete mediating effect (95% CI, mediating effect: 51.56%) in the reduction of the progression of NTLs by PCSK9 inhibitors, and there was a possible mediating effect of IL-8 (90% CI), and sIL-2R (90% CI). CONCLUSIONS: LDL-c, hs-CRP, IL-8, and sIL-2R may be the key characteristic risk factors for the rapid progression of NTLs post-PCI, and combining these parameters might predict the rapid progression of NTLs post-PCI. The application of PCSK9 inhibitors had a negative correlation with the rapid progression of NTLs. In addition to the significant LDL-c-lowering, PCSK9 inhibitors may reduce the rapid progression of NTLs by reducing local inflammation of plaque. TRIAL REGISTRATION: ChiCTR2200058529; Date of registration: 2022-04-10.

FGF4 ameliorates the liver inflammation by reducing M1 macrophage polarization in experimental autoimmune hepatitis.

BACKGROUND: The global prevalence of autoimmune hepatitis (AIH) is increasing due in part to the lack of effective pharmacotherapies. Growing evidence suggests that fibroblast growth factor 4 (FGF4) is crucial for diverse aspects of liver pathophysiology. However, its role in AIH remains unknown. Therefore, we investigated whether FGF4 can regulate M1 macrophage and thereby help treat liver inflammation in AIH. METHODS: We obtained transcriptome-sequencing and clinical data for patients with AIH. Mice were injected with concanavalin A to induce experimental autoimmune hepatitis (EAH). The mechanism of action of FGF4 was examined using macrophage cell lines and bone marrow-derived macrophages. RESULTS: We observed higher expression of markers associated with M1 and M2 macrophages in patients with AIH than that in individuals without AIH. EAH mice showed greater M1-macrophage polarization than control mice. The expression of M1-macrophage markers correlated positively with FGF4 expression. The loss of hepatic Fgf4 aggravated hepatic inflammation by increasing the abundance of M1 macrophages. In contrast, the pharmacological administration of FGF4 mitigated hepatic inflammation by reducing M1-macrophage levels. The efficacy of FGF4 treatment was compromised following the in vivo clearance of macrophage populations. Mechanistically, FGF4 treatment activated the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-signal pathway in macrophages, which led to reduced M1 macrophages and hepatic inflammation. CONCLUSION: We identified FGF4 as a novel M1/M2 macrophage-phenotype regulator that acts through the PI3K-AKT-signaling pathway, suggesting that FGF4 may represent a novel target for treating inflammation in patients with AIH.

Nanoplastic at environmentally relevant concentrations induces toxicity across multiple generations associated with inhibition in germline G protein-coupled receptor CED-1 in Caenorhabditis elegans.

Nanoplastics at environmentally relevant concentrations (ERCs) could cause transgenerational toxicity on organisms. Caenorhabditis elegans is an important model for the study of transgenerational toxicology of pollutants. Nevertheless, the underlying mechanisms for the control of transgenerational nanoplastic toxicity by germline signals remain largely unclear. In C. elegans, exposure to 1-100 µg/L polystyrene nanoparticle (PS-NP) decreased expression of germline ced-1 encoding a G protein-coupled receptor at parental generation (P0-G). After PS-NP exposure at P0-G, transgenerational decrease in germline ced-1 expression could be detected. Meanwhile, the susceptibility to transgenerational PS-NP toxicity was observed in ced-1(RNAi) animals. After PS-NP exposure at P0-G, germline RNAi of ced-1 increased expressions of met-2 and set-6 encoding histone methylation transferases. The susceptibility of ced-1(RNAi) to transgenerational PS-NP toxicity could be inhibited by RNAi of met-2 and set-6. Moreover, in PS-NP exposed met-2(RNAi) and set-6(RNAi) nematodes, expressions of ins-39, wrt-3, and/or efn-3 encoding secreted ligands were decreased. Therefore, our results demonstrated that inhibition in germline CED-1 mediated the toxicity induction of nanoplastics at ERCs across multiple generations in nematodes.

A systematic evaluation of computational methods for cell segmentation.

Cell segmentation is a fundamental task in analyzing biomedical images. Many computational methods have been developed for cell segmentation and instance segmentation, but their performances are not well understood in various scenarios. We systematically evaluated the performance of 18 segmentation methods to perform cell nuclei and whole cell segmentation using light microscopy and fluorescence staining images. We found that general-purpose methods incorporating the attention mechanism exhibit the best overall performance. We identified various factors influencing segmentation performances, including image channels, choice of training data, and cell morphology, and evaluated the generalizability of methods across image modalities. We also provide guidelines for choosing the optimal segmentation methods in various real application scenarios. We developed Seggal, an online resource for downloading segmentation models already pre-trained with various tissue and cell types, substantially reducing the time and effort for training cell segmentation models.

Configurational Isomerization-Induced Orientation Switching: Non-Fused Ring Dipodal Phosphonic Acids as Hole-Extraction Layers for Efficient Organic Solar Cells.

Phosphonic acid (PA) self-assembled molecules have recently emerged as efficient hole-extraction layers (HELs) for organic solar cells (OSCs). However, the structural effects of PAs on their self-assembly behaviors on indium tin oxide (ITO) and thus photovoltaic performance remain obscure. Herein, we present a novel class of PAs, namely "non-fused ring dipodal phosphonic acids" (NFR-DPAs), featuring simple and malleable non-fused ring backbones and dipodal phosphonic acid anchoring groups. The efficacy of configurational isomerism in modulating the photoelectronic properties and switching molecular orientation of PAs atop electrodes results in distinct substrate surface energy and electronic characteristics. The NFR-DPA with linear (C2h symmetry) and brominated backbone exhibits favorable face-on orientation and enhanced work function modification capability compared to its angular (C2v symmetry) and non-brominated counterparts. This makes it versatile HELs in mitigating interfacial resistance for energy barrier-free hole collection, and affording optimal active layer morphology, which results in an impressive efficiency of 19.11% with a low voltage loss of 0.52 V for binary OSC devices and an excellent efficiency of 19.66% for ternary OSC devices. This study presents a new dimension to design PA-based HELs for high-performance OSCs.

Thienyltriazine Triamides: Thickness Insensitive Interlayer Materials Featuring Fine-tuned Optoelectronic and Aggregation Characters for Efficient Organic Solar Cells.

A novel class of thienyltriazine triamides (TTTAs) was facile synthesized and firstly used as cathode interlayers (CILs) for organic solar cells (OSCs). By utilizing different aromatic arms and pendant polar groups, their optoelectronic properties and aggregation behaviors were effectively modulated. The combination of thienyltriazine (TT) core, naphthylamide arm and imidazole pendant group endows TT-N-M with suitable energy levels, intensified work function tunability, higher conductivity, and well-balanced crystallinity and film-forming ability, boosting both the performance and stability of OSCs significantly. Remarkably, the solar cell efficiency remains stable at around 90% of the optimal efficiency even as the interlayer thickness varied from 5 to 95 nm, demonstrating its insensitivity to thickness. Moreover, TT-N-M exhibits compatibility with various active layer systems, achieving a maximum efficiency of 19.60% for single-junction solar cell. Its exceptional tolerance to thickness fluctuations and performance establishes a new benchmark for multi-armed CIL-based OSCs, also positioning them among the most high-performing CIL materials documented thus far. This work not only broadens the scope of CIL materials for OSCs but also offers deep insights into design strategies and structure-properties relationships, being beneficial for the future development of more efficient CIL materials for organic optoelectronic applications.

A Comparison of Tranexamic Acid in Nasal Versus Sinus Surgeries: a Systematic Review and Meta-Analysis.

Nasal surgeries (e.g.: rhinoplasties, septoplasties) and sinus surgeries (e.g.: Functional Endoscopic Sinus Surgeries) are common procedures in Otorhinolaryngology. Tranexamic acid (TXA), an antifibrinolytic drug, has been increasingly utilized to reduce hemorrhage recently. While close in proximity anatomically, the bleeding nature of sinus and nasal surgeries may differ. We present the first meta-analysis that has reviewed both nasal and sinus surgery collectively and compares the two. Pubmed, Embase, Cochrane Library and WoS were searched until April 2023. Outcomes of interest include Boezart Scoring, clotting time, postoperative complications and surgical field quality. 27 Studies were assessed, of which 25 studies were evaluated quantitatively. Of the 27 studies, 15 studies involved Sinus surgery while 12 involved Nasal surgery. The use of tranexamic acid was notably beneficial in the evaluation of blood loss, reduction of operating time, surgical field quality and surgeon satisfaction. TXA has proven to be efficacious in both nasal and sinus surgeries to varying degrees. TXA has more effects in sinus surgeries compared to nasal surgeries in objective markers such as reducing blood loss and operating time, but the converse occurs for subjective markers such as surgeon satisfaction scores. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04579-x.

Development of an integrated online deposition and corrosion monitoring system in a full-scale solid waste CFB boiler.

Solid waste incineration is a clean and sustainable approach for solid waste management. However, ash deposition and corrosion remain a critical issue due to fuel's inherent enrichment of alkali chlorine. This study develops an integrated online deposition and corrosion monitoring system to enhance the operational safety and efficiency of solid waste incineration boilers. This system combines linear polarization resistance (LPR) for corrosion rate estimation with heat flux measurements for ash deposition analysis. It can offer a novel approach for real-time monitoring of heat exchangers' safety during solid waste combustion. It was deployed in a full-scale circulating fluidized bed (CFB) boiler that purely combust solid wastes. Key findings demonstrate the system's capability to deliver continuous, real-time data, crucial for the dynamic control of combustion processes and the maintenance of heat transfer surfaces. Its robust diagnostic capabilities were evident across various scenarios. Specially, initial corrosion rates sharply increase with deposition rates due to the enrichment of alkali chlorine on inner deposit layer, in which chlorine serves as a catalyst, facilitating the rapid penetration and aggravation of corrosion by other agents. As deposit further buildup, the corrosion rate steadily decreases along with surface temperature, highlighting a dynamic interaction. Moreover, measured corrosion rates can quickly response to temperature variations. Such multi-process online monitoring system provide more possibilities to investigate the inherent interaction between deposition and corrosion. Therefore, this work offers insights that could significantly influence operational strategies, maintenance protocols, and the overall reliability of waste-to-energy technologies.

Exposure to 6-PPD quinone enhances glycogen accumulation in Caenorhabditiselegans.

Glycogen metabolism is an important biological process for organisms. In Caenorhabditis elegans, effect of 6-PPD quinone (6-PPDQ) on glycogen accumulation and underlying mechanism were examined. Exposure to 6-PPDQ (1 and 10 µg/L) increased glycogen accumulation. Meanwhile, exposure to 6-PPDQ (1 and 10 µg/L) increased expression of gsy-1 encoding glycogen synthase and decreased expression of pygl-1 encoding glycogen phosphorylase. In 6-PPDQ exposed animals, glycogen content and glycogen accumulation were inhibited by RNAi of gsy-1 and enhanced by RNAi of pygl-1. RNAi of gsy-1 increased pygl-1 expression, and RNAi of pygl-1 increased gsy-1 expression after 6-PPDQ exposure. In 6-PPDQ exposed nematodes, daf-16 and aak-2 expressions were decreased and glycogen accumulation was suppressed by RNAi of daf-16 and aak-2, suggesting alteration in daf-16 and aak-2 expressions did not mediate glycogen accumulation. Moreover, resistance to 6-PPDQ toxicity on locomotion and brood size was observed in gsy-1(RNAi) animals, and susceptibility to 6-PPDQ toxicity was found in pygl-1(RNAi) animals. Therefore, glycogen accumulation could be enhanced by exposure to 6-PPDQ in nematodes. In addition, alteration in expressions of gsy-1 and pygl-1 governing this enhancement in glycogen accumulation mediated induction of 6-PPDQ toxicity.