[Clinical manifestation and imaging diagnostic analysis of fat embolism syndrome].

OBJECTIVE: To explore characteristics of clinical and imaging findings in patients with fat embolism syndrome. METHODS: From January 2021 to October 2022,clinical manifestations of 13 patients with fat embolism due to fracture or orthopaedic surgery were retrospectively analyzed,including 11 males and 2 females,aged from 17 to 60 years old. Mental and respiratory abnormalities and changes in vital signs occurred after admission or after surgery,and patient's chest and brain imaging results were abnormal. The patient's mental and respiratory abnormalities,vital signs,chest and brain imaging results were continuously monitored. RESULTS: The main clinical manifestations of fat embolism syndrome were abnormal pulmonary respiration in 13 patients,abnormal central nervous function in 7 patients,and spotted rash in 2 patients. Chest CT showed diffuse distribution of ground glass shadows in 13 patients,and severe symptoms were "snowstorm". Nine patients with ground glass fusion consolidation,5 patients with multiple nodules and 4 patients accompanied by bilateral pleural effusion. Head CT findings of 5 patients were negative,and head MRI findings of 1 patient showed multiple T1WI low signal,T2WI high signal shadow,DWI high signal shadow,and "starry sky sign" in basal ganglia,radiative crown,hemioval center,thalamus,frontal parietal cortex and subcortex. CONCLUSION: Fat embolism syndrome has a high mortality rate. Clinical manifestations of respiratory system and nervous system are not specific,and the skin spot rash has a characteristic manifestation. The "blizzard" sign is the specific manifestation of chest X-ray and CT examination of fat embolism,and the "starry sky" sign is the typical manifestation of diffusion-weighted sequence of brain MRI examination of fat embolism.

A Green Asymmetric Bicyclic Co-Solvent Molecule for High-Voltage Aqueous Lithium-Ion Batteries.

Hybridizing aqueous electrolytes with organic co-solvents can effectively expand the voltage window of aqueous electrolytes while reducing salt usage, but most reported co-solvents are usually flammable and toxic, hardly achieving compatibility between safety and electrochemical performance. Here, a new non-flammable and non-toxic low-salt-concentration (1.85 m) aqueous electrolyte is reported using the green co-solvent isosorbide dimethyl ether (IDE). Owing to its unique 3D molecular structure, IDE can form a five-membered ring structure by binding the Li ion. The steric hindrance effect from IDE weakens its solvation ability, generating anion-participated solvation structures that produce a robust and uniform LiF-rich solid electrolyte interphase layer while containing elastic IDE-derived organics. Moreover, the multiple O atoms in IDE can effectively regulate the intermolecular hydrogen bonding networks, reducing H2O molecule activity and expanding the electrochemical window. Such unique solvation structures and optimized hydrogen bonding networks enabled by IDE effectively suppress electrode/electrolyte interfacial side reactions, achieving a 4.3 V voltage window. The as-developed Li4Ti5O12(LTO)||LiMn2O4(LMO) full cell delivers outstanding cycling performance over 450 cycles at 2 C. The proposed green hybrid aqueous electrolyte provides a new pathway for developing high-voltage aqueous lithium batteries.

Abnormal expression of PRKAG2-AS results in dysfunction of cardiomyocytes through regulating PRKAG2 transcription by interacting with PPARG.

The role of PRKAG2 in the maintenance of heart function is well established, but little is known about how PRKAG2 is regulated in cardiomyocytes. In this study, we investigated the role of the lncRNA PRKAG2-AS, which is present at the PRKAG2 promoter, in the regulation of PRKAG2 expression. PRKAG2-AS expression was predominantly nuclear, as determined by RNA nucleoplasmic separation and fluorescence in situ hybridization. Knockdown of PRKAG2-AS in the nucleus, but not the cytoplasm, significantly decreased the expression of PRKAG2b and PRKAG2d. Interestingly, we found that PRKAG2-AS and its target genes, PRKAG2b and PRKAG2d, were reduced in the hearts of patients with ischemic cardiomyopathy, suggesting a potential role for PRKAG2-AS in myocardial ischemia. Indeed, knockdown of PRKAG2-AS in the nucleus resulted in apoptosis of cardiomyocytes. We further elucidated the mechanism by which PRKAG2-AS regulates PRKAG2 transcription by identifying 58 PRKAG2-AS interacting proteins. Among them, PPARG was selected for further investigation based on its correlation and potential interaction with PRKAG2-AS in regulating transcription. Overexpression of PPARG, or its activation with rosiglitazone, led to a significant increase in the expression of PRKAG2b and PRKAG2d in cardiomyocytes, which could be attenuated by PRKAG2-AS knockdown. This finding suggests that PRKAG2-AS mediates, at least partially, the protective effects of rosiglitazone on hypoxia-induced apoptosis. However, given the risk of rosiglitazone in heart failure, we also examined the involvement of PRKAG2-AS in this condition and found that PRKAG2-AS, as well as PRKAG2b and PRKAG2d, was elevated in hearts with dilated cardiomyopathy (DCM) and that overexpression of PRKAG2-AS led to a significant increase in PRKAG2b and PRKAG2d expression, indicating that up-regulation of PRKAG2-AS may contribute to the mechanism of heart failure by promoting transcription of PRKAG2. Consequently, proper expression of PRKAG2-AS is essential for maintaining cardiomyocyte function, and aberrant PRKAG2-AS expression induced by hypoxia or other stimuli may cause cardiac dysfunction.

Rapid and sensitive screening of multiple polycyclic aromatic hydrocarbons by a reusable fluorescent sensor array.

Simple and rapid sensing of polycyclic aromatic hydrocarbons (PAHs) remains a great technical challenge due to their chemical stability and structural similarity. Here, a simple, sensitive and cost-effective sensing strategy is proposed to detect multiple PAHs by utilizing the inner filter effect (IFE) and a reusable fluorescent sensor array consisting of four polyvinyl alcohol (PVA) composite carbon quantum dots (CDs) film sensors. The CDs/PVA films have a wide and tunable excitation range, which provide sufficient spectral overlap with PAHs and ensure the efficient occurrence of IFE. Under different excitations, the diverse UV absorption capacities of PAHs resulted in diverse spectral responses, enabling a unique chemical fingerprint for each PAH. Upon multivariate pattern recognition analysis, the array rendered high-throughput discrimination and sensitive quantification of 16 priority PAHs with 100% classification accuracy and detection limit as low as 57 nM. Moreover, the rapid and accurate screening of multiple environmental samples were also realized with the results consistent with high-performance liquid chromatography. This IFE-based reusable array is readily prepared, green and feasible, which exhibits great potential in environmental analysis and brings an advanced strategy to high-throughput sensing of more pollutants with similar structures and lack of recognition sites.

Carbon Nanotube Supported Molybdenum Carbide as Robust Electrocatalyst for Efficient Hydrogen Evolution Reaction.

Molybdenum carbide is considered to be one of the most competitive catalysts for hydrogen evolution reaction (HER) regarding its high catalytic activity and superior corrosion resistance. But the low electrical conductivity and poor interfacial contact with the current collector greatly inhibit its practical application capability. Herein, carbon nanotube (CNT) supported molybdenum carbide was assembled via electrostatic adsorption combined with complex bonding. The N-doped molybdenum carbide nanocrystals were uniformly anchored on the surfaces of amino CNTs, which depressed the agglomeration of nanoparticles while strengthening the migration of electrons. The optimized catalyst (250-800-2h) showed exceptional electrocatalytic performance towards HER under both acidic and alkaline conditions. Especially in 0.5 M H2SO4 solution, the 250-800-2h catalyst exhibited a low overpotential of 136 mV at a current density of 10 mA/cm2 (η10) with the Tafel slope of 49.9 mV dec-1, and the overpotential only increased 8 mV after 20,000 cycles of stability test. The active corrosive experiment revealed that more exposure to high-activity γ-Mo2N promoted the specific mass activity of Mo, thus, maintaining the catalytic durability of the catalyst.

A Reconfigurable Differential-to-Single-Ended Autonomous Current Adaptation Buffer Amplifier Suitable for Biomedical Applications.

A reconfigurable differential-to-single-ended autonomous current adaptation buffer amplifier (ACABA) is proposed. The ACABA, based on floating-gate technologies, is a capacitive circuit, of which output DC level and bandwidth can be adjusted by programming charges on floating nodes. The gain is variable by switching different amounts of capacitors without altering the output DC level. Without extra sensing and control circuitries, the current consumption of the proposed ACABA increases spontaneously when the input signal is fast or large, achieving a high slew rate. The supply current dwindles back to the low quiescent level autonomously when the output voltage reaches equilibrium. Therefore, the proposed ACABA is power-efficient and suitable for processing physiological signals. A prototype ACABA has been designed and fabricated in a [Formula: see text] CMOS process occupying an area of [Formula: see text]. When loaded by a [Formula: see text] capacitor, it consumes [Formula: see text] to achieve a unity-gain bandwidth of [Formula: see text] with a measured IIP2 value of [Formula: see text] and a slew rate of [Formula: see text].

Evaluation of Risk Scores to Predict Pediatric Severe Asthma Exacerbations.

BACKGROUND: Asthma exacerbations commonly lead to unplanned health care utilization and are costly. Early identification of children at increased risk of asthma exacerbations would allow a proactive management approach. OBJECTIVE: We evaluated common asthma risk factors to predict the probability of exacerbation for individual children aged 0-21 years using data from the electronic medical record (EMR). METHODS: We analyzed longitudinal EMR data for over 3000 participants with asthma seen at Cincinnati Children's Hospital Medical Center over a 7-year period. The study population was divided into 3 age groups: 0-4, 5-11, and 12-21 years. Each age group was divided into a derivation cohort and a validation cohort, which were used to build a risk score model. We predicted risk of exacerbation in the next 12 months, validated the scores by risk stratum, and developed a clinical tool to determine the risk level based on this model. RESULTS: Risk model results were confirmed with validation cohorts by calendar year and age groups. Race, allergic sensitization, and smoke exposure were each important risk factors in the 0-4 age group. Abnormal spirometry and obesity were more sensitive predictors of exacerbation in children >12 years. For each age group, a higher expanded score was associated with a higher predicted probability of an asthma exacerbation in the subsequent year. CONCLUSION: This asthma exacerbation prediction model, and the associated clinical tool, may assist clinicians in identifying children at high risk for exacerbation that may benefit from more aggressive management and targeted risk mitigation.

Crystal structure of RahU, an aegerolysin protein from the human pathogen Pseudomonas aeruginosa, and its interaction with membrane ceramide phosphorylethanolamine.

Aegerolysins are proteins produced by bacteria, fungi, plants and protozoa. The most studied fungal aegerolysins share a common property of interacting with membranes enriched with cholesterol in combination with either sphingomyelin or ceramide phosphorylethanolamine (CPE), major sphingolipids in the cell membranes of vertebrates and invertebrates, respectively. However, genome analyses show a particularly high frequency of aegerolysin genes in bacteria, including the pathogenic genera Pseudomonas and Vibrio; these are human pathogens of high clinical relevance and can thrive in a variety of other species. The knowledge on bacterial aegerolysin-lipid interactions is scarce. We show that Pseudomonas aeruginosa aegerolysin RahU interacts with CPE, but not with sphingomyelin-enriched artificial membranes, and that RahU interacts with the insect cell line producing CPE. We report crystal structures of RahU alone and in complex with tris(hydroxymethyl)aminomethane (Tris), which, like the phosphorylethanolamine head group of CPE, contains a primary amine. The RahU structures reveal that the two loops proximal to the amino terminus form a cavity that accommodates Tris, and that the flexibility of these two loops is important for this interaction. We show that Tris interferes with CPE-enriched membranes for binding to RahU, implying on the importance of the ligand cavity between the loops and its proximity in RahU membrane interaction. We further support this by studying the interaction of single amino acid substitution mutants of RahU with the CPE-enriched membranes. Our results thus represent a starting point for a better understanding of the role of P. aeruginosa RahU, and possibly other bacterial aegerolysins, in bacterial interactions with other organisms.

Effects of different straw biochars on soil organic carbon, nitrogen, available phosphorus, and enzyme activity in paddy soil.

Biochar is widely used as a soil amendment. Enzyme activity is an important factor that reflects soil metabolic activity, and is involved in biochemical processes such as organic matter decomposition and nutrient cycling in soils. However, the effects of biochar prepared for different straw materials on soil enzyme activity and soil nutrients are rarely studied. Through pot experiments, the effects of different straw (wheat, rice, maize) biochars (obtained by pyrolysis at 500 °C) on soil organic carbon, nitrogen, available phosphorus, and enzyme activity were studied in paddy soil. The results showed that the addition of biochar increased the soil organic carbon content, which gradually decreased with the extension of the rice growth period. The soil ammonium nitrogen content gradually decreased as the rice growth period continued; however, the soil nitrate nitrogen content first decreased and then increased over the rice growth period. Soil invertase, phosphatase, and urease activity first increased and then decreased, and the enzyme activity was the highest at the heading stage of rice. At this time, there were also significant correlations between enzyme activity and carbon, nitrogen, and phosphorus levels, except in the case of soil urease activity. The geometric mean of the investigated enzyme activities was the highest after amendment with rice straw biochar. These results indicate that the response of enzyme activity to biochar depends on the biochar feedstock and the rice growth stage.

Platelets Endocytose Viral Particles and Are Activated via TLR (Toll-Like Receptor) Signaling.

OBJECTIVE: Thrombocytopenia is associated with many viral infections suggesting virions interact with and affect platelets. Consistently, viral particles are seen inside platelets, and platelet activation markers are detected in viremic patients. In this article, we sought mechanistic insights into these virion/platelet interactions by examining how platelets endocytose, traffic, and are activated by a model virion. Approach and Results: Using fluorescently tagged HIV-1 pseudovirions, 3-dimensional structured illumination microscopy, and transgenic mouse models, we probed the interactions between platelets and virions. Mouse platelets used known endocytic machinery, that is, dynamin, VAMP (vesicle-associated membrane protein)-3, and Arf6 (ADP-ribosylation factor 6), to take up and traffic HIV-1 pseudovirions. Endocytosed HIV-1 pseudovirions trafficked through early (Rab4+) and late endosomes (Rab7+), and then to an LC3+ (microtubule-associated protein 1A/1B-light chain 3) compartment. Incubation with virions induced IRAK4 (interleukin 1 receptor-associated kinase 4), Akt (protein kinase B), and IKK (IκB kinase) activation, granule secretion, and platelet-leukocyte aggregate formation. This activation required TLRs (Toll-like receptors) and MyD88 (myeloid differentiation primary response protein 88) but was less extensive and slower than activation with thrombin. In vivo, HIV-1 pseudovirions injection led to virion uptake and platelet activation, as measured by IKK activation, platelet-leukocyte aggregate formation, and mild thrombocytopenia. All were decreased in VAMP-3-/- and, megakaryocyte/platelet-specific, Arf6-/- mice. Similar platelet activation profiles (increased platelet-leukocyte aggregates, plasma platelet factor 4, and phospho-IκBα) were detected in newly diagnosed and antiretroviral therapy-controlled HIV-1+ patients. CONCLUSIONS: Collectively, our data provide mechanistic insights into the cell biology of how platelets endocytose and process virions. We propose a mechanism by which platelets sample the circulation and respond to potential pathogens that they take up.

Effects of modification and magnetization of rice straw derived biochar on adsorption of tetracycline from water.

Rice straw derived biochar shows low-cost superiority as a potential adsorbent in tetracycline (TC) removal, but limited by its poor adsorption capacity and N, P leaking risk. Herein, an alkali-acid combined and magnetization method was proposed for its modification. The sorption kinetic and isotherm data showed modification enhanced the performance for tetracycline removal with adsorption capacity up to 98.33 mg·g-1. The strong adsorption mechanisms were dominated by hydrogen bonding and pore-filling effect due to the increase of specific surface area and pore volume. Furthermore, the effect of pH was insignificant over a pH range from 3 to 10. The strong competition between ionic and TC was identified, where Ca2+ and PO43- markedly inhibited the sorption. The enhanced TC adsorption, strong N and P removal, easy magnetic recovery, and good reusability in water samples entrusted it with good potential for wastewater treatment and rice straw resource disposal.

Enrichment behavior of contemporary PAHs and legacy PCBs at the sea-surface microlayer in harbor water.

Polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) in the sea-surface microlayer (SML) and sub-surface water (SSW) were analyzed in and around Kaohsiung Harbor. The results confirm SML enrichments for PAHs, but PCBs less significantly, since PAHs are still produced while PCBs had banned years ago. However, PCBs still leak to the environment from contaminated sites. The results showed the sources and transport of PAHs and PCBs were different, but both are enriched in the SML. Total particulate PAHs at most sites are below the toxicity thresholds, with a few individual PAHs between the effects range-low and effect range-median even higher than the effect range-median. Total particulate PCBs might cause occasionally adverse effects in sensitive species and pose a risk to the organisms. The particulate phase in the SML poses a higher risk to the marine ecosystem than in the SSW although not all organisms will make direct use of the microlayer. Principal component analysis (PCA) of PAHs indicated the important contribution of traffic engine emission in the particulate samples of the SML and SSW and revealed that probably the petroleum pollutants are a predominant source for the dissolved phase. Cluster analysis revealed that PAH-PCB patterns in the river and anchorage channels were different to those in the wetlands and open harbor. However, PCA of PCBs showed differences in the congener profiles for the two phases, with highly chlorinated PCBs more abundant in particles, while less chlorinated PCBs were more abundant in dissolved.

Patient-derived pancreas-on-a-chip to model cystic fibrosis-related disorders.

Cystic fibrosis (CF) is a genetic disorder caused by defective CF Transmembrane Conductance Regulator (CFTR) function. Insulin producing pancreatic islets are located in close proximity to the pancreatic duct and there is a possibility of impaired cell-cell signaling between pancreatic ductal epithelial cells (PDECs) and islet cells as causative in CF. To study this possibility, we present an in vitro co-culturing system, pancreas-on-a-chip. Furthermore, we present an efficient method to micro dissect patient-derived human pancreatic ducts from pancreatic remnant cell pellets, followed by the isolation of PDECs. Here we show that defective CFTR function in PDECs directly reduced insulin secretion in islet cells significantly. This uniquely developed pancreatic function monitoring tool will help to study CF-related disorders in vitro, as a system to monitor cell-cell functional interaction of PDECs and pancreatic islets, characterize appropriate therapeutic measures and further our understanding of pancreatic function.

Targeting DNAJB9, a novel ER luminal co-chaperone, to rescue ΔF508-CFTR.

The molecular mechanism of Endoplasmic Reticulum-associated degradation (ERAD) of Cystic fibrosis transmembrane-conductance regulator (CFTR) is largely unknown. Particularly, it is unknown what ER luminal factor(s) are involved in ERAD. Herein, we used ProtoArray to identify an ER luminal co-chaperone, DNAJB9, which can directly interact with CFTR. For both WT- and ΔF508 (deletion of phenylalanine at position 508, the most common CF-causing mutant)-CFTR, knockdown of DNAJB9 by siRNA increased their expression levels on the cell surface and, consequently, upregulated their function. Furthermore, genetic ablation of DNAJB9 in WT mice increased CFTR expression and enhanced CFTR-dependent fluid secretion in enteroids. Importantly, DNAJB9 deficiency upregulated enteroids' fluid secretion in CF mice (homozygous for ΔF508), and silencing one allele of DNAJB9 is sufficient to rescue ΔF508-CFTR in vitro and in vivo, suggesting that DNAJB9 may be a rate-limiting factor in CFTR ERAD pathway. Our studies identified the first ER luminal co-chaperone involved in CFTR ERAD, and DNAJB9 could be a novel therapeutic target for CF.

Autophagy in Platelets.

Anucleate platelets are produced by fragmentation of megakaryocytes. Platelets circulate in the bloodstream for a finite period: upon vessel injury, they are activated to participate in hemostasis; upon senescence, unused platelets are cleared. Platelet hypofunction leads to bleeding. Conversely, pathogenic platelet activation leads to occlusive events that precipitate strokes and heart attacks. Recently, we and others have shown that autophagy occurs in platelets and is important for platelet production and normal functions including hemostasis and thrombosis. Due to the unique properties of platelets, such as their lack of nuclei and their propensity for activation, methods for studying platelet autophagy must be specifically tailored. Here, we describe useful methods for examining autophagy in both human and mouse platelets.

Revealing the Activity Distribution of a Single Nanocatalyst by Locating Single Nanobubbles with Super-Resolution Microscopy.

It is challenging to uncover the catalytic activity at different locations of a single nanocatalyst for gas-generating reactions in real time. This research uses super-resolution microscopy to localize the center of single nanobubbles and reveal the local activity distribution at several to tens of nanometers accuracy. The distances between the centers of the nanobubbles and the center of the nanoplate usually distribute in a certain range from 0 to 500 nm, with the maximum population exhibiting at ∼200 nm. This research also shows that more nanobubbles appear near the tips of the Pd-Ag nanoplate compared with the edges, which indicates higher activity at the tips. In addition, the relationship between the location, lifetime, and turnover rate of the nanobubbles was also carefully studied. This work presents an effective, high-resolution method to localize the activity distribution of nanocatalysts during gas-generating reactions, such as photocatalytic water splitting, dehydrogenation, and electro-oxidation.

Personalized medicine in CF: from modulator development to therapy for cystic fibrosis patients with rare CFTR mutations.

Cystic fibrosis (CF) is the most common life-shortening genetic disease affecting ~1 in 3,500 of the Caucasian population. CF is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. To date, more than 2,000 CFTR mutations have been identified, which produce a wide range of phenotypes. The CFTR protein, a chloride channel, is normally expressed on epithelial cells lining the lung, gut, and exocrine glands. Mutations in CFTR have led to pleiotropic effects in CF patients and have resulted in early morbidity and mortality. Research has focused on identifying small molecules, or modulators, that can restore CFTR function. In recent years, two modulators, ivacaftor (Kalydeco) and lumacaftor/ivacaftor (Orkambi), have been approved by the U.S. Food and Drug Administration to treat CF patients with certain CFTR mutations. The development of these modulators has served as proof-of-concept that targeting CFTR by modulators is a viable therapeutic option. Efforts to discover new modulators that could deliver a wider and greater clinical benefit are still ongoing. However, traditional randomized controlled trials (RCTs) require large numbers of patients and become impracticable to test the modulators' efficacy in CF patients with CFTR mutations at frequencies much lower than 1%, suggesting the need for personalized medicine in these CF patients.

Dynamic cycling of t-SNARE acylation regulates platelet exocytosis.

Platelets regulate vascular integrity by secreting a host of molecules that promote hemostasis and its sequelae. Given the importance of platelet exocytosis, it is critical to understand how it is controlled. The t-SNAREs, SNAP-23 and syntaxin-11, lack classical transmembrane domains (TMDs), yet both are associated with platelet membranes and redistributed into cholesterol-dependent lipid rafts when platelets are activated. Using metabolic labeling and hydroxylamine (HA)/HCl treatment, we showed that both contain thioester-linked acyl groups. Mass spectrometry mapping further showed that syntaxin-11 was modified on cysteine 275, 279, 280, 282, 283, and 285, and SNAP-23 was modified on cysteine 79, 80, 83, 85, and 87. Interestingly, metabolic labeling studies showed incorporation of [3H]palmitate into the t-SNAREs increased although the protein levels were unchanged, suggesting that acylation turns over on the two t-SNAREs in resting platelets. Exogenously added fatty acids did compete with [3H]palmitate for t-SNARE labeling. To determine the effects of acylation, we measured aggregation, ADP/ATP release, as well as P-selectin exposure in platelets treated with the acyltransferase inhibitor cerulenin or the thioesterase inhibitor palmostatin B. We found that cerulenin pretreatment inhibited t-SNARE acylation and platelet function in a dose- and time-dependent manner whereas palmostatin B had no detectable effect. Interestingly, pretreatment with palmostatin B blocked the inhibitory effects of cerulenin, suggesting that maintaining the acylation state is important for platelet function. Thus, our work shows that t-SNARE acylation is actively cycling in platelets and suggests that the enzymes regulating protein acylation could be potential targets to control platelet exocytosis in vivo.