A hub gene signature as a therapeutic target and biomarker for sepsis and geriatric sepsis-induced ARDS concomitant with COVID-19 infection

BackgroundCOVID-19 and sepsis represent formidable public health challenges, characterized by incompletely elucidated molecular mechanisms. Elucidating the interplay between COVID-19 and sepsis, particularly in geriatric patients suffering from sepsis-induced acute respiratory distress syndrome (ARDS), is of paramount importance for identifying potential therapeutic interventions to mitigate hospitalization and mortality risks.MethodsWe employed bioinformatics and systems biology approaches to identify hub genes, shared pathways, molecular biomarkers, and candidate therapeutics for managing sepsis and sepsis-induced ARDS in the context of COVID-19 infection, as well as co-existing or sequentially occurring infections. We corroborated these hub genes utilizing murine sepsis-ARDS models and blood samples derived from geriatric patients afflicted by sepsis-induced ARDS.ResultsOur investigation revealed 189 differentially expressed genes (DEGs) shared among COVID-19 and sepsis datasets. We constructed a protein-protein interaction network, unearthing pivotal hub genes and modules. Notably, nine hub genes displayed significant alterations and correlations with critical inflammatory mediators of pulmonary injury in murine septic lungs. Simultaneously, 12 displayed significant changes and correlations with a neutrophil-recruiting chemokine in geriatric patients with sepsis-induced ARDS. Of these, six hub genes (CD247, CD2, CD40LG, KLRB1, LCN2, RETN) showed significant alterations across COVID-19, sepsis, and geriatric sepsis-induced ARDS. Our single-cell RNA sequencing analysis of hub genes across diverse immune cell types furnished insights into disease pathogenesis. Functional analysis underscored the interconnection between sepsis/sepsis-ARDS and COVID-19, enabling us to pinpoint potential therapeutic targets, transcription factor-gene interactions, DEG-microRNA co-regulatory networks, and prospective drug and chemical compound interactions involving hub genes.ConclusionOur investigation offers potential therapeutic targets/biomarkers, sheds light on the immune response in geriatric patients with sepsis-induced ARDS, emphasizes the association between sepsis/sepsis-ARDS and COVID-19, and proposes prospective alternative pathways for targeted therapeutic interventions

Investigation of the Properties of TixCr1-xN Coatings Prepared by Cathodic Arc Deposition

AbstractThe structure, composition and mechanical properties of TixCr1-xN coatings have been investigated. Processing by cathodic arc evaporation using cathodes with different arc currents was performed to obtain coatings with compositions x=0.52, x=0.59, x=0.68, x=0.72 and x=0.81, The TixCr1-xN hard coatings were characterized by nanoindentation, scanning electron microscopy and X-ray diffraction. The results showed the coatings consisted of B1-NaCl type cubic structure, the Cr content promoted a (200) preferred crystallographic orientation and has a dramatic influence on the hardness of TixCr1-xN coatings, which indicted the alloy-strengthening of the Cr element on TiN-based coatings

Multi-Cell-to-Multi-Cell Battery Equalization in Series Battery Packs Based on Variable Duty Cycle

Batteries are widely used in our lives, but the inevitable inconsistencies in series-connected battery packs will seriously impact their energy utilization, cycle life and even jeopardize their safety in use. This paper proposes a balancing topology structure combining Buck-Boost circuit and switch array to reduce this inconsistency. This structure can realize multi-cell-to-multi-cell (MC2MC) battery balancing by controlling the switch array and having a fast balancing speed, easy expansion and few magnetic components. Then, the operation principle of the proposed balancing topology is analyzed, and the simulation model is verified. In addition, the effects of switching frequency and voltage difference on the equalization effect are further analyzed. The results show that the higher the switching frequency, the lower the time efficiency, but the higher the energy efficiency. The voltage difference significantly impacts the duty cycle, so it is absolutely necessary to introduce a variable duty cycle in the multi-cell-to-multi-cell equalization. Finally, eight series batteries are selected for simulation verification. The simulation results show that, compared with any-cell-to-any-cell (AC2AC) equalization, the time efficiency of multi-cell-to-multi-cell equalization is improved considerably, the energy efficiency is improved slightly, and the variance of the completed equalization is reduced, demonstrating the excellent performance of multi-cell-to-multi-cell equalization

Gestational weight gain and adverse pregnancy outcomes: a prospective cohort study

Objective To assess the associations of gestational weight gain (GWG) in early and late pregnancy with subsequent risks of adverse pregnancy outcomes in Chinese women.Design Prospective cohort study.Setting Shanghai, China.Participants We studied 2630 nulliparous singleton pregnant women with complete data on weight gain in early (≤17 weeks of gestation) and late (>17 weeks) pregnancy in the Shanghai Birth Cohort.Methods GWG was standardised into z-scores by gestational age and categorised as low (z-score <−1), normal (−1 to +1) and high (>1). The adjusted relative risks (aRRs) and 95%CIs were estimated through log-binomial regression models. Interaction effects between GWG and some other adjustment factors were tested, further stratified analyses were performed separately where interaction terms were significant.Outcome measures Adverse maternal and neonatal outcomes.Results Independent from GWG in late pregnancy, higher GWG in early pregnancy was associated with higher risks of gestational diabetes mellitus (aRR: 1.66; 95% CI: 1.11 to 2.48), caesarean section (aRR: 1.21; 95% CI: 1.05 to 1.39) and prolonged hospitalisation (aRR: 1.56; 95% CI: 1.03 to 2.38). Higher GWG in late pregnancy was independently associated with higher risks of caesarean section (aRR: 1.24; 95% CI: 1.09 to 1.41), large for gestational age (aRR: 2.01; 95% CI: 1.50 to 2.7) and macrosomia (aRR: 1.90; 95% CI: 1.30 to 2.78). In addition, the risk of gestational hypertension increased significantly with increased total GWG (aRR: 1.78; 95% CI: 1.14 to 2.76). The effects of GWG in late pregnancy on maternal and neonatal outcomes were significantly different between the women bearing a female and the women bearing male fetus.Conclusion The GWG associations with adverse pregnancy outcomes differ at early and late pregnancy, and there may be effect modification by fetal sex in the association of GWG in late pregnancy with some pregnancy outcomes

Adapt to Environment Sudden Changes by Learning a Context Sensitive Policy

Dealing with real-world reinforcement learning (RL) tasks, we shall be aware that the environment may have sudden changes. We expect that a robust policy is able to handle such changes and adapt to the new environment rapidly. Context-based meta reinforcement learning aims at learning environment adaptable policies. These methods adopt a context encoder to perceive the environment on-the-fly, following which a contextual policy makes environment adaptive decisions according to the context. However, previous methods show lagged and unstable context extraction, which are hard to handle sudden changes well. This paper proposes an environment sensitive contextual policy learning (ESCP) approach, in order to improve both the sensitivity and the robustness of context encoding. ESCP is composed of three key components: variance minimization that forces a rapid and stable encoding of the environment context, relational matrix determinant maximization that avoids trivial solutions, and a history-truncated recurrent neural network model that avoids old memory interference. We use a grid-world task and 5 locomotion controlling tasks with changing parameters to empirically assess our algorithm. Experiment results show that in environments with both in-distribution and out-of-distribution parameter changes, ESCP can not only better recover the environment encoding, but also adapt more rapidly to the post-change environment (10x faster in the grid-world) while the return performance is kept or improved, compared with state-of-the-art meta RL methods

LCST phase behavior of benzo-21-crown-7 with different alkyl chains

The introduction of hydrophobic units into crown ethers can dramatically decrease the critical transition temperature of LCST and realize macroscopic phase separation at low to moderate temperature and concentration. Minor modifications in the chemical structure of crown ethers (benzo-21-crown-7, B21C7s) can effectively control the thermo-responsive properties

Stress–Strain Model for Freezing Silty Clay under Frost Heave Based on Modified Takashi’s Equation

In analyzing frost heave, researchers often simplify the compressive modulus of freezing soil by considering it as a constant or only as a function of temperature. However, it is a critical parameter characterizing the stress–strain behavior of soil and a variable that is influenced by many other parameters. Hence, herein several one-dimensional freezing experiments are conducted on silty clay in an open system subjected to multistage freezing by considering the compressive modulus as a variable. First, freezing soil under multistage freezing is divided into several layers according to the frozen fringe theory. Then, the correlation between the freezing rate and temperature gradient within each freezing soil layer is investigated. Takashi’s equation for frost heave analysis is modified to extend its application conditions by replacing its freezing rate term with a temperature gradient term. A mechanical model for the stress–strain behavior of freezing soil under the action of frost heave is derived within the theoretical framework of nonlinear elasticity, in which a method for determining the compressive modulus of freezing soil with temperature gradient, overburden pressure, and cooling temperature variables is proposed. This study further enhances our understanding of the typical mechanical behavior of saturated freezing silty clay under frost heave action

Drivers of carbon emissions in China’s tourism industry

This manuscript examines the driving forces of carbon emissions in China’s tourism industry. Tourism carbon emissions are estimated by constructing China’s Economic-Environmental Accounts (EEA). Analysis is divided into five-time intervals and specifically examines intensity, scale, structure, and technology. Following index and structural decomposition methods, changes in tourism carbon emissions were segmented into sixteen economy-wide and tourism-specific driving forces. Results demonstrate that direct and total tourism carbon emissions compose 0.7% and 2.7% of total carbon emissions in China. Analysis revealed the positive driver of tourism emissions was domestic tourists, representing 140.4% increase in direct and 263.4% increase in total tourism carbon emissions. Modelling identified energy intensity as the main negative driver in total and direct tourism carbon emissions, especially for national economic sectors (−208.6%) and non-transport tourism sectors (−33.8%). Future research should focus on the measurement and implementation of mitigation policies for domestic tourism emissions.</p

compositionandoriginoflipidbiomarkersinthesurfacesedimentsfromthesouthernchallengerdeepmarianatrench

The surface sediments collected from the southern Mariana Trench at water depths between ca. 4900m and 7068m were studied using lipid biomarker analyses to reveal the origin and distribution of organic matters. For all samples, an unresolved complex mixture (UCM) was present in the hydrocarbon fractions, wherein resistant component tricyclic terpanes were detected but C 27 –C 29 regular steranes and hopanes indicative of a higher molecular weight range of petroleum were almost absent. This biomarker distribution patterns suggested that the UCM and tricyclic terpanes may be introduced by contamination of diesel fuels or shipping activities and oil seepage elsewhere. The well-developed faults and strike-slip faults in the Mariana subduction zone may serve as passages for the petroleum hydrocarbons. In addition, the relative high contents of even n -alkanes and low Carbon Preference Indices indicated that the n -alkanes were mainly derived from bacteria or algae. For GDGTs, the predominance of GDGT-0 and crenarchaeol, together with low GDGT-0 n -alkanes C 19 –C 22 and the n -fatty acids C 20:0 –C 22:0 were depleted in 13 C by 3‰ compared to n -alkanes C 16 –C 18 and the n -fatty acids C 14:0 –C 18:0 , respectively, which was interpreted to result from the preferential reaction of fatty acid fragments with carbon “lighter” terminal carboxyl groups during carbon chain elongation from the precursors to products. The abundance of total alkanes, carboxylic acids, alcohols and total lipids were generally increased along the down-going seaward plate, suggesting the lateral organic matter inputs play an important role in organic matter accumulation in hadal trenches. The extremely high contents of biomarkers in sample BC11 were most likely related to trench topography and current dynamics, since the lower steepness caused by graben texture and proximity to the trench axis may result in higher sedimentation rate. This paper, for the first time, showed the biomarker patterns in surface sediments of the Mariana Trench and shed light on biogeochemistry of the hardly reached trench environment

Composition and origin of lipid biomarkers in the surface sediments from the southern Challenger Deep, Mariana Trench

The surface sediments collected from the southern Mariana Trench at water depths between ca. 4900 m and 7068 m were studied using lipid biomarker analyses to reveal the origin and distribution of organic matters. For all samples, an unresolved complex mixture (UCM) was present in the hydrocarbon fractions, wherein resistant component tricyclic terpanes were detected but C27–C29 regular steranes and hopanes indicative of a higher molecular weight range of petroleum were almost absent. This biomarker distribution patterns suggested that the UCM and tricyclic terpanes may be introduced by contamination of diesel fuels or shipping activities and oil seepage elsewhere. The well-developed faults and strike-slip faults in the Mariana subduction zone may serve as passages for the petroleum hydrocarbons. In addition, the relative high contents of even n-alkanes and low Carbon Preference Indices indicated that the n-alkanes were mainly derived from bacteria or algae. For GDGTs, the predominance of GDGT-0 and crenarchaeol, together with low GDGT-0/Crenarchaeol ratios (ranging from 0.86 to 1.64), suggests that the GDGTs in samples from the southern Mariana Trench were mainly derived from planktic Thaumarchaeota. However, the high GDGT-0/crenarchaeol ratio (10.5) in sample BC07 suggests that the GDGTs probably were introduced by methanogens in a more anoxic environment. Furthermore, the n-alkanes C19–C22 and the n-fatty acids C20:0–C22:0 were depleted in 13C by 3‰ compared to n-alkanes C16–C18 and the n-fatty acids C14:0–C18:0, respectively, which was interpreted to result from the preferential reaction of fatty acid fragments with carbon “lighter” terminal carboxyl groups during carbon chain elongation from the precursors to products. The abundance of total alkanes, carboxylic acids, alcohols and total lipids were generally increased along the down-going seaward plate, suggesting the lateral organic matter inputs play an important role in organic matter accumulation in hadal trenches. The extremely high contents of biomarkers in sample BC11 were most likely related to trench topography and current dynamics, since the lower steepness caused by graben texture and proximity to the trench axis may result in higher sedimentation rate. This paper, for the first time, showed the biomarker patterns in surface sediments of the Mariana Trench and shed light on biogeochemistry of the hardly reached trench environment. Keywords: Mariana Trench, Lipid biomarkers, Organic matter, Topography, Hydrodynamic