Development of prognostic models for predicting 90-day neurological function and mortality after cardiac arrest.

BACKGROUND: The survivors of cardiac arrest experienced vary extent of hypoxic ischemic brain injury causing mortality and long-term neurologic disability. However, there is still a need to develop robust and reliable prognostic models that can accurately predict these outcomes. OBJECTIVES: To establish reliable models for predicting 90-day neurological function and mortality in adult ICU patients recovering from cardiac arrest. METHODS: We enrolled patients who had recovered from cardiac arrest at Binhaiwan Central Hospital of Dongguan, from January 2018 to July 2021. The study's primary outcome was 90-day neurological function, assessed and divided into two categories using the Cerebral Performance Category (CPC) scale: either good (CPC 1-2) or poor (CPC 3-5). The secondary outcome was 90-day mortality. We analyzed the relationships between risk factors and outcomes individually. A total of four models were developed: two multivariable logistic regression models (models 1 and 2) for predicting neurological function, and two Cox regression models (models 3 and 4) for predicting mortality. Models 2 and 4 included new neurological biomarkers as predictor variables, while models 1 and 3 excluded. We evaluated calibration, discrimination, clinical utility, and relative performance to establish superiority between the models. RESULTS: Model 1 incorporates variables such as gender, site of cardiopulmonary resuscitation (CPR), total CPR time, and acute physiology and chronic health evaluation II (APACHE II) score, while model 2 includes gender, site of CPR, APACHE II score, and serum level of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1). Model 2 outperforms model 1, showcasing a superior area under the receiver operating characteristic curve (AUC) of 0.97 compared to 0.83. Additionally, model 2 exhibits improved accuracy, sensitivity, and specificity. The decision curve analysis confirms the net benefit of model 2. Similarly, models 3 and 4 are designed to predict 90-day mortality. Model 3 incorporates the variables such as site of CPR, total CPR time, and APACHE II score, while model 4 includes APACHE II score, total CPR time, and serum level of UCH-L1. Model 4 outperforms model 3, showcasing an AUC of 0.926 and a C-index of 0.830. The clinical decision curve analysis also confirms the net benefit of model 4. CONCLUSIONS: By integrating new neurological biomarkers, we have successfully developed enhanced models that can predict 90-day neurological function and mortality outcomes more accurately.

Biotic communities inspired proteinosome-based aggregation for enhancing utilization rate of enzyme.

Compared with the individuals, the collective behavior of biotic communities could show certain superior characteristics. Inspired by this idea and based on the conjugation between phenylboronic acid-grafted mesoporous silica nanoparticles and the polysaccharide functionalized membrane of proteinosomes, a type of proteinosomes-based aggregations was constructed. We demonstrated the emergent characteristics of proteinosomes aggregations including accelerated settling velocity and population surviving by sacrificing outside members for the inside. Moreover, this kind of "hand in hand" architecture provided the proteinosomes aggregations with the characteristic of resistance to the negative pressure phagocytosis of micropipette, as well as enhancing utilization rate of the encapsulated enzymes. Overall, it is anticipated that the construction and application of proteinosomes aggregations could contribute to advance the functionality of life-like assembled biomaterial in another way.

A Class of Biocompatible Dye-Protein Complex Optical Nanoprobes.

Molecular organic dyes are classic fluorescent nanoprobes finding tremendous uses in biological and life sciences. Yet, they suffer from low brightness, poor photostability, and lack of functional groups for bioconjugation. Here, we describe a class of biocompatible dye-protein optical nanoprobes, which show long-time photostability, superbrightness, and enriched functional groups. These nanoprobes utilize apoferritin (an intracellular protein for iron stores and release) to encase appropriate molecular organic dyes to produce on-demand fluorescence in aqueous solution. A pH-driven dissociation-reconstitution process of apoferritin subunits allows substantial incorporation of hydrophilic (aggregation caused quenching, ACQ) or hydrophobic (aggregation induced enhancement, AIE) dye molecules into the protein nanocavity (8 nm), producing monodispersed dye-apoferritin nanoparticles (apo-dye-NPs, ∼12 nm). As compared with single dye monomer, single apo-dye-NPs possess hundreds of times larger molar extinction coefficient and 2 orders of magnitude higher absolute luminescence quantum yield (up to 45-fold), multiplying fluorescence brightness up to 2778-fold. We show that varying the type of incorporated dyes entails a precise control over nanoprobe emission profile tunable in a broad spectral range of 370-1300 nm. Mechanical investigations indicate that the diversified microstructures of nanocavity inner surface are able to conform ACQ dyes at reasonable space interval while providing protein-guided-stacking for AIE dyes, thus enhancing fluorescence quantum yield through confining intermolecular quenching and intramolecular rotation. Moreover, apo-dye-NPs are able to emit stable fluorescence (over 13 min) without quenching in confocal imaging of HepG2 cancer cell under ultrahigh laser irradiance (1.3 × 106 W/cm2). These superb properties make them suitable, as demonstrated in this work, for long-term super-resolved structured illumination microscopic cell imaging (spatial resolution, 117 nm) over 48 h, near-infrared (NIR) fluorescence angiography imaging of whole-body blood vessels (spatial resolution, 380 µm), and NIR photoacoustic imaging of liver in vivo.

Construction of Hybrid Bi-microcompartments with Exocytosis-Inspired Behavior toward Fast Temperature-Modulated Transportation of Living Organisms.

Inspired by the unique characteristics of living cells, the creation of life-inspired functional ensembles is a rapidly expanding research topic, enabling transformative applications in various disciplines. Herein, we report a facile method for the fabrication of phospholipid and block copolymer hybrid bi-microcompartments via spontaneous asymmetric assembly at the water/tributyrin interface, whereby the temperature-mediated dewetting of the inner microcompartments allowed for exocytosis to occur in the constructed system. The exocytosis location and commencement time could be controlled by the buoyancy of the inner microcompartment and temperature, respectively. Furthermore, the constructed bi-microcompartments showed excellent biocompatibility and a universal loading capacity toward cargoes of widely ranging sizes; thus, the proliferation and temperature-programmed transportation of living organisms was achieved. Our results highlight opportunities for the development of complex mesoscale dynamic ensembles with life-inspired behaviors and provide a novel platform for on-demand transport of various living organisms.

Fusion-Induced Structural and Functional Evolution in Binary Emulsion Communities.

The biomimetic dynamic behaviours of emulsions are receiving increasing attention from the broad scientific community; however, the spatiotemporal control and functionalization of emulsions based on simple fusion-induced method is rarely mentioned. A design for protein-stabilized oil-in-water droplets and phospholipid-stabilized oil-in-water droplets is described and a substance-diffusion-mediated fusion mechanism proposed within these two different emulsion communities. Significantly, a range of fusion-induced high-order behaviours were successfully demonstrated including competitive fusion, fusion-induced evolution in membrane complexity, and diversified structures with the formation of Janus or various patchy morphologies, fusion-induced membrane maturation, as well as fusion-induced multifunctionalization with a directional motility behaviour. These results highlight the fusion-induced diverse dynamic behaviours in complex emulsions communities and provide a platform for advancing versatile applications of emulsions.

Dynamic Behaviour in Microcompartments.

Compartmentalisation is recognised to be a primary step for the assembly of non-living matter towards the construction of life-like microensembles. To date, a host of hollow microcompartments with various functionalities have been widely developed. Within this respect, given that dynamic behaviour is one of the fundamental features to distinguish living ensembles from those that are non-living, the design and construction of microcompartments with various dynamic behaviours are attracting considerable interest from a wide range of research communities. Significantly, the created dynamic microcompartments could also be widely used as chassis for further bottom-up design towards building protocell models by integrating and booting up necessary biological information. Herein, strategies to install the various motility behaviours into microcompartments, including haptotaxis, chemotaxis and gravitaxis, are summarized in the anticipation of inspiring more designs towards creating various advanced active microcompartments, and contributing new techniques to the ultimate goal of constructing a basic living unit entirely from non-living components.

Synthesis and biological evaluation of deuterated sofosbuvir analogs as HCV NS5B inhibitors with enhanced pharmacokinetic properties.

A series of deuterated sofosbuvir analogs were designed and prepared with the aim of improving their pharmacokinetic properties. The devised synthetic routes allow for site-selective deuterium incorporation with high levels of isotopic purity. As expected, the deuterated analogs (37-44) are as efficacious as sofosbuvir when tested in vitro inhibition of viral replication (replicon) assays. Compared with sofosbuvir, deuterated analog 40 displays improved in vivo pharmacokinetics profiles in rats and dogs in terms of the metabolite and the prodrug. The Cmax and area under the curve (AUC) of 40 in dogs were increased by 3.4- and 2.7-fold, respectively. Due to the enhanced pharmacokinetic properties and the great synthetic advantage of an inexpensive deuterium source (D2 O) for 40, it was chosen for further investigation.

Heat stress combined with lipopolysaccharide alter the activity and superficial molecules of peripheral monocytes.

The purpose of this study was to focus on the underlying relationship between the hyperactivity for the peripheral monocytes and heat stroke by investigating the inflammatory oxidative activity of and the expression of superficial molecules. Peripheral blood samples were collected from 10 healthy adult volunteers. Human blood monocytes were isolated by density gradient centrifugation and sequent adherent culture. The objectives were divided into four groups: 43°C heat stress combined with lipopolysaccharide (LPS) group, 43°C heat stress group, LPS group, and control group. There were 10 cases in each group. An enzyme-linked immunosorbent assay (ELISA) test was used to measure the concentrations of supernatant inflammatory mediators (tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß) and interleukin-10 (IL-10)). After loaded by 2,7-Dichlorodi-hydrofluorescein-diacetate (DCFHDA) fluorescent probe, intracellular reactive oxygen species (ROS) levels were determined by a flow cytometry. After fluorescent microspheres incubation, the phagocytosis of monocytes was observed under a fluorescent microscope. Respectively, the flow cytometry and Western blot were used to evaluate the level of triggering receptor expressed on myeloid cells-1 (TREM-1) and Toll-like receptor-4 (TLR-4) on the monocytes. Furthermore, the mRNA expression of TREM-1 and TLR-4 was detected by real-time polymerase chain reaction (RT-PCR). The heat stress combined with LPS stimulation promoted the peripheral monocytes to produce inflammatory mediators (TNF-α, IL-1ß, and IL-10) and release ROS. Otherwise, such complex strike significantly suppressed the phagocytic activity of monocytes in peripheral blood. Moreover, the expression of TREM-1, TLR-4 and CD86 was measured by the flow cytometry on peripheral monocytes which were respectively promoted by the union of heat stress and LPS. The results of Western blot and RT-PCR demonstrated the similar kinetics on these superficial molecules (TREM-1, TLR-4, and CD86) stimulated by the combination of heat stress and LPS. The underlying mechanism of the dysfunction for the peripheral monocytes may be related to the abnormal expression of superficial molecules TREM-1, TLR-4, and CD86 on the monocytes induced by heat stress and LPS.

Autonomic Behaviors in Lipase-Active Oil Droplets.

Developing self-fueled micro-reactor droplets with programmable autonomic behaviors provides a step towards smart liquid dispersions comprising motile microscale objects. Herein, we prepare aqueous suspensions of lipase-coated oil globules comprising a mixture of a triglyceride substrate (tributyrin, 1,2,3-tributylglycerol) and a low-density oil (polydimethylsiloxane, PDMS) and describe a range of active behaviors based on controlled enzyme-mediated consumption of individual droplets under non-equilibrium conditions. Encapsulation of the lipase-coated lipid/PDMS droplets into a model protocell as energy-rich sub-compartments is demonstrated as an internalized mechanism for activating protocell buoyancy. Taken together, our results highlight opportunities for the regulation of autonomic behavior in enzyme-powered oil droplets and provide a new platform for increasing the functionality and energization of synthetic protocells.

RETRACTED: Long non-coding RNA NEAT1 plays an important role in sepsis-induced acute kidney injury by targeting miR-204 and modulating the NF-κB pathway.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of authors with the approval of the Editor-in-Chief. Panel 'LPS+sh-NEAT1' from Figure 2C appears similar to panel 'si-PVT1' from Figure 2A of the article published by Wei Huang, Xiuwen Lan, Xueting Li, Dawei Wang, Yinghao Sun, Qian Wang, Hong Gao and Kaijiang Yu in the International Immunopharmacology 47 (2017) 134-140 http://dx.doi.org/10.1016/j.intimp.2017.03.030 and panel 'Control' from Figure 1D of the article published by Xiaodi Liu, Chengying Hong, Shipin Wu, Shiling Song, Zhi Yang, Lin Cao, Tongwei Song and Ying Yang in the Journal of Cellular Biochemistry 120 (2019) 11331-11341 https://doi.org/10.1002/jcb.28409. Given the comments of Dr Elisabeth Bik https://scienceintegritydigest.com/2020/02/21/the-tadpole-paper-mill/ regarding this article, the journal requested the corresponding author to provide the raw data. However, the author was not able to fulfil this request.

Microcirculatory Disorders and Protective Role of Xuebijing in Severe Heat Stroke.

This study was conducted to explore underlying mechanism of microcirculation dysfunction and protectiverole of Xuebijing in heat stroke. Forty rats were divided into: control, vehicle + heat stress (HS), superoxide dismutase (SOD) + HS, and Xuebijing + HS groups. Rats in heat stress groups were subjected to continuous heat stress in infant incubator 1 h after tail vein injection of the tested compound and spinotrapezius preparation. Velocity of blood flow through micro-vessels and vascular diameter were detected in real time. Another 27 rats were divided into: vehicle, SOD, and Xuebijing groups, then further divided into three subgroups each: control, Tcore = 38 °C, Tcore = 41 °C. Rats were sacrificed, and spinotrapezius single-cell suspensions were prepared for detecting SOD and reactive oxygen species (ROS). The results showed that heat stress decreased SOD activity, increased ROS levels, and reduced the blood flow rate. Xuebijing increased SOD activity, decreased ROS levels and exhibited a protective effect in terms of blood flow rate but was less protective than SOD. The survival time in Xuebijing + HS group was longer than that in vehicle group but shorter than that in SOD + HS group. The results suggested Xuebijing could decrease ROS levels and have protective effects in severe heat stroke.

Impact of individual characteristics on sonographic IVC diameter and the IVC diameter/aorta diameter index.

BACKGROUND: The inferior vena cava (IVC) parameters, including its diameter and collapsibility index have been evaluated for fluid status for over 30 years, but little is known about the impacts of patient characteristics on IVC parameters. The purpose of this study was to explore the relationships between individual patient characteristics and IVC parameters in healthy Chinese adult volunteers. METHODS: From February 2012 to May 2012, 216 healthy volunteers older than the age of 18 years were consecutively enrolled in our study. The individual characteristics and presence or absence of hypertension of each participant were recorded. Sonographic measurements of IVC and abdominal aorta diameter (Ao) were performed (DP-6900; Mindray, Shenzhen, China). RESULTS: Volunteers ranged in age from 18 to 84 years (43.7 ± 7.8 years), and 50.5% were males. In univariate analyses, maximum IVC diameter (IVCmax) was negatively correlated with age (years) (r = -0.171, P = .012) and positively correlated with sex (men) (r = 0.174, P = .01), height (centimeters) (r = 0.281, P < .001), and body surface area (square meters) (r = 0.173, P = .011). The IVC/Ao index was negatively correlated with age (years) (r = -0.326, P < .001), waist circumference (centimeters) (r = -0.176, P = .01), body mass index (r = -0.173, P = .011), and hypertension (r = -0.186, P = .006). None of the patient characteristics were significantly correlated with percentage collapse of the IVC. Height (centimeters) was the sole significant predictor of IVCmax (R(2) = 0.079, P < .001). Age (years) and body mass index (kilogram/square meter) were independent predictors of the IVC/Ao index (R(2) = 0.123; P < .001 and P = .046, respectively). CONCLUSIONS: The percentage collapse of IVC and the IVCmax are not substantially influenced by patient characteristics. In contrast, the IVC/Ao index is more susceptible to patient characteristics than IVC.

[Pretreatment with Xuebijing injection alleviates systemic inflammatory response induced by severe heat-stroke via ameliorating intestinal injury in rats].

OBJECTIVE: To observe the effect of Xuebijing injection pretreatment on systemic inflammatory response induced by severe heat-stroke, and to investigate the mechanism of alleviation of intestinal injury in rats. METHODS: Thirty-six healthy adult male Wistar rats with grade SPF were randomly assigned into three groups with randomized number method, namely sham group, severe heat-stroke model group, and Xuebijing pretreatment group ( XBJ group ), with 12 rats in each group. The animals were placed in a pre-warm chamber [ temperature ( 40±2 ) centigrade, humidity ( 65±5 )% ] in order to induce typical heat-stroke. The duration of heat-stress was 60 minutes, while the animals in sham group were exposed to ambient temperature of 25 centigrade. Arterial blood samples were collected at the beginning and the end of heat-stress, the concentrations of tumor necrosis factor-α( TNF-α), interleukins ( IL-1ß, IL-6 ), and lipopolysaccharide ( LPS ) in peripheral blood were determined by enzyme linked immunosorbent assay ( ELISA ). The intestinal tissues were harvested after heat-stress, and the pathological changes in intestine tissues were observed after hematoxylin-eosin ( HE ) staining and under optical microscope. The pathological injury scores were calculated. Immunohistochemistry was performed to determine inducible nitric oxide synthase ( iNOS ) expression in intestinal tissue. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling ( TUNEL ) staining. Western Blot was used to measure the tight junction protein occludin expression. RESULTS: The concentrations of TNF-α, IL-1ß, IL-6 and LPS in blood of the rats after heat-stress in model group were significantly higher than those of sham group [ TNF-α ( µg/L ): 443.00±110.10 vs. 98.36±44.61, IL-1ß ( µg/L ): 436.37±163.64 vs.64.24±16.15, IL-6 ( µg/L ): 342.70±92.42 vs. 54.40±13.22, LPS ( µg/L ): 0.68±0.22 vs. 0.09±0.02, all P < 0.01 ], but the levels of these parameters in XBJ group were significantly lower than those of model group [ TNF-α ( µg/L ): 340.45±68.57 vs. 443.00±110.10, IL-1ß ( µg/L ): 191.33±82.78 vs. 436.37±163.64, IL-6 ( µg/L ): 192.21±37.89 vs. 342.70±92.42, LPS ( µg/L ): 0.43±0.17 vs. 0.68±0.22, all P < 0.01 ]. Infiltration of inflammatory cells, necrosis and hemorrhage in intestinal mucosa were found in the intestine of heat-stroke animals in model group. The pathological lesions in XBJ group were milder than those of model group, with a decreased pathological injury score compared with model group ( 2.10±1.15 vs. 3.20±0.67, P < 0.01 ). The expression of iNOS and apoptosis of cells in intestinal tissue in model group were increased compared with that of sham group, but they were significantly less marked in XBJ group compared with model group [ iNOS ( adjusted A value ): 0.32±0.15 vs. 0.74±0.17, apoptotic index: 0.23±0.08 vs. 0.56±0.07, both P < 0.01 ]. The order of expression for occludin protein from high to low was sham group, XBJ group and model group ( A value was 0.96±0.25, 0.62±0.20, 0.33±0.11, respectively ). Furthermore, there was significant difference in the expression of occludin protein between model group and both XBJ group and sham group ( both P < 0.01 ). CONCLUSIONS: Xuebijing injection alleviates inflammation and endotoxemia produced by severe heat-stroke in rats. The mechanism may be related to amelioration of oxidative injury, apoptosis, and dysfunction of tight junction protein occludin expression.