Induced Manipulation of Atomically Dispersed Cobalt through S Vacancy for Photocatalytic Water Splitting: Asymmetric Coordination and Dynamic Evolution.

It is still a challenge to construct single-atom level reduction and oxidation sites in single-component photocatalyst by manipulating coordination configuration for photocatalytic water splitting. Herein, the atomically dispersed asymmetric configuration of six-coordinated Co-S2O4 (two exposed S atoms, two OH groups, and two Co─O─Zn bonds) suspending on ZnIn2S4 nanosheets verified by combining experimental analysis with theoretical calculation, is applied into photocatalytic water splitting. The Co-S2O4 site immobilized by Vs acts as oxidation sites to guide electrons transferring to neighboring independent S atom, achieving efficient separation of reduction and oxidation sites. It is worth mentioning that stabilized Co-S2O4 configuration show dynamic structure evolution to highly active Co-S1O4 configuration (one exposed S atom, one OH group, and three Co─O─Zn bonds) in reaction, which lowers energy barrier of transition state for H2O activization. Ultimately, the optimized photocatalyst exhibits excellent photocatalytic activity for water splitting (H2: 80.13 µmol g-1 h-1, O2: 37.81 µmol g-1 h-1) and outstanding stability than that of multicomponent photocatalysts due to dynamic and reversible evolution between stable Co-S2O4 configuration and active Co-S1O4 configuration. This work demonstrates new cognitions on immobilized strategy through vacancy inducing, manipulating coordination configuration, and dynamic evolution mechanism of single-atom level catalytic site in photocatalytic water splitting.

Theoretical Insights into the Mechanism and Origin of Solvent-Dependent Selectivity in the Cyclization of Propargyl Alcohols for the Divergent Synthesis of N-Heterocycles.

This study elucidates the mechanisms and principles governing chemoselectivity in synthesizing two distinct N-heterocycles, benzimidazole thiazine and benzothiazole imidazole, through BF3•OEt2-catalyzed cyclization reactions of propargyl alcohols with benzimidazole thiols. Employing density functional theory calculations, we highlight the crucial role of fluorine source in influencing chemoselectivity. In DCM, BF3, as the catalytic center, coordinates with propargyl alcohol's hydroxyl group to form a precursor. Conversely, in DMF, [BF2•DMF]+, formed from DMF and BF3•OEt2, acts as the catalytic center, activating the propargyl alcohol's hydroxyl group. The mechanisms in both solvents involve sequential steps: B-O bond formation, C-O bond cleavage, S-C bond formation, hydrogen atom transfer (HAT), cyclization, and deprotonation. A notable difference is the HAT process: in DCM, it follows a 1,5-HAT process, while in DMF, BF4- formation from DMF and BF3•OEt2 provides a fluorine source and introduces steric hindrance, favoring a 1,6-HAT process and leading to unique chemoselectivity. This pioneering research showcases the impact of DMF on cyclization reactions, offering valuable insights for comprehending and designing reactions driven by fluorine sources. Crucially, our results propose an innovative reaction mechanism featuring lower potential energy surfaces, enhancing our understanding of the intricate interplay among reactants, catalysts, and solvents.

Decreased DTI-ALPS index in delirium: a preliminary MRI study.

PURPOSE: Delirium is linked to brain abnormalities, yet the role of the glymphatic system is not well understood. This study aims to examine alterations in brain physiology in delirium by using diffusion-tensor imaging (DTI) to assess water diffusion along the perivascular space (ALPS) and to explore its correlation with clinical symptoms. METHODS: We examined 15 patients with delirium and 15 healthy controls, measuring water diffusion metrics along the x-, y-, and z-axes in both projection and association fibers to determine the DTI-ALPS index. We used a general linear model, adjusted for age and sex, to compare the DTI-ALPS index between groups. We also investigated the relationship between the DTI-ALPS index and clinical symptoms using partial correlations. RESULTS: Patients with delirium exhibited significantly lower DTI-ALPS indices compared to healthy controls (1.25 ± 0.15 vs. 1.38 ± 0.10, t = 2.903, p = 0.007; 1.27 ± 0.16 vs. 1.39 ± 0.08, 1.22 ± 0.16 vs. 1.37 ± 0.14, t = 2.617, p = 0.014; t = 2.719, p = 0.011; respectively). However, there was no significant correlation between the DTI-ALPS index and clinical symptoms. CONCLUSION: Our findings indicate a decreased DTI-ALPS index in patients with delirium, suggesting potential alterations in brain physiology that may contribute to the pathophysiology of delirium. This study provides new insights into the mechanisms underlying delirium.

A lung disease diagnosis algorithm based on 2D spectral features of ultrasound RF signals.

Lung diseases are commonly diagnosed based on clinical pathological indications criteria and radiological imaging tools (e.g., X-rays and CT). During a pandemic like COVID-19, the use of ultrasound imaging devices has broadened for emergency examinations by taking their unique advantages such as portability, real-time detection, easy operation and no radiation. This provides a rapid, safe, and cost-effective imaging modality for screening lung diseases. However, the current pulmonary ultrasound diagnosis mainly relies on the subjective assessments of sonographers, which has high requirements for the operator's professional ability and clinical experience. In this study, we proposed an objective and quantifiable algorithm for the diagnosis of lung diseases that utilizes two-dimensional (2D) spectral features of ultrasound radiofrequency (RF) signals. The ultrasound data samples consisted of a set of RF signal frames, which were collected by professional sonographers. In each case, a region of interest of uniform size was delineated along the pleural line. The standard deviation curve of the 2D spatial spectrum was calculated and smoothed. A linear fit was applied to the high-frequency segment of the processed data curve, and the slope of the fitted line was defined as the frequency spectrum standard deviation slope (FSSDS). Based on the current data, the method exhibited a superior diagnostic sensitivity of 98% and an accuracy of 91% for the identification of lung diseases. The area under the curve obtained by the current method exceeded the results obtained that interpreted by professional sonographers, which indicated that the current method could provide strong support for the clinical ultrasound diagnosis of lung diseases.

Causes and global, regional, and national burdens of traumatic brain injury from 1990 to 2019.

PURPOSE: Traumatic brain injury (TBI), currently a major global public health problem, imposes a significant economic burden on society and families. We aimed to quantify and predict the incidence and severity of TBI by analyzing its incidence, prevalence, and years lived with disability (YLDs). The epidemiological changes in TBI from 1990 to 2019 were described and updated to provide a reference for developing prevention, treatment, and incidence-reducing measures for TBI. METHODS: A secondary analysis was performed on the incidence, prevalence, and YLDs of TBI by sex, age group, and region (n = 21,204 countries and territories) between 1990 and 2019 using the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Proportions in the age-standardized incidence rate due to underlying causes of TBI and proportions of minor and moderate or severe TBI were also reported. RESULTS: In 2019, there were 27.16 million (95% uncertainty intervals (UI): 23.36 - 31.42) new cases of TBI worldwide, with age-standardized incidence and prevalence rates of 346 per 100,000 population (95% UI: 298-401) and 599 per 100,000 population (95% UI: 573-627), respectively. From 1990 to 2019, there were no significant trends in global age-standardized incidence (estimated annual percentage changes: -0.11%, 95% UI: -0.18% - -0.04%) or prevalence (estimated annual percentage changes: 0.01%, 95% UI: -0.04% - 0.06%). TBI caused 7.08 million (95% UI: 5.00 - 9.59) YLDs in 2019, with age-standardized rates of 86.5 per 100,000 population (95% UI: 61.1 - 117.2). In 2019, the countries with higher incidence rates were mainly distributed in Central Europe, Eastern Europe, and Australia. The 2019 global age-standardized incidence rate was higher in males than in females. The 2019 global incidence of moderate and severe TBI was 182.7 per 100,000 population, accounting for 52.8% of all TBI, with falls and road traffic injuries being the main causes in most regions. CONCLUSIONS: The incidence of moderate and severe TBI was slightly higher in 2019, and TBI still accounts for a significant portion of the global injury burden. The likelihood of moderate to severe TBI and the trend of major injury under each injury cause from 1990 to 2019 and the characteristics of injury mechanisms in each age group are presented, providing a basis for further research on injury causes in each age group and the future establishment of corresponding policies and protective measures.

Synergetic approaches of fucoidan and trabectedin complex coated PLGA nanoparticles effectively suppresses proliferation and induce apoptosis for the treatment on non-small cell lung cancer.

Traditional methods of treating lung cancer have not been very effective, contributing to the disease's high incidence and death rate. As a result, Fn/Tn-PLGA NPs, a novel directed fucoidan and trabectedin complex loaded PLGA nanoparticle, were produced to investigate the role of developing therapeutic strategies for NSCLC and A549 cell lines. Quantitative real-time polymerase chain reaction was used to examine protein expression and mRNA expression, respectively. Protein activity was knocked down using specific inhibitors and short disrupting RNA transfection. Lastly, cancer cell lines H1299 and A549 were subjected to an in vitro cytotoxicity experiment. Commercial assays were used to assess the levels of cell viability, ROS and proliferation found that Fn/Tn-PLGA NPs effectively killed lung cancer cells. To examine cell death, annexin flow cytometry was employed. In addition, a scratch-wound assay was conducted to assess the migration effects of Fn/Tn-PLGA NPs in a laboratory setting. Finally, PLGA NPs covered with a mix of fucoidan and trabectedin could be a good vehicle for targeting cancerous tissues with chemotherapeutic drugs.

Adsorption Behavior and Kinetics of 1,4-Dioxane by Carbon Aerogel.

1,4-dioxane is a potential carcinogen in water and is difficult to deal with due to its robust cycloether bond and complete miscibility with water. To remove 1,4-dioxane in an economically viable and environmentally friendly way, a series of carbon aerogels were synthesized as adsorbents for 1,4-dioxane. The experiment results showed that adsorption performances were closely related to the preparation conditions of carbon aerogels, such as the molar ratio, heating rate, pyrolysis temperature and residence time, which were carefully controlled. Scanning electron microscope analysis revealed the presence of a three-dimensional porous network structure in carbon aerogels. Brunauer-Emmett-Teller analysis results demonstrated an increase in specific surface area (673.89 m2/g) and total pore volume after carbonization, with an increase in mesoporous porosity and a decrease in microporosity. When considering each variable individually, the highest specific surface area of prepared carbon aerogels was achieved at a pyrolysis temperature of 800 °C, a holding time of 1 h, and a heating rate of 2 °C/min. Under optimal experimental conditions, the adsorption removal of 1,4-dioxane by carbon aerogels exceeded 95%, following quasi-second-order kinetics and Langmuir isothermal adsorption isotherms, indicating that monolayer adsorption on the surface of carbon aerogels occurred. The maximum adsorption capacity obtained was 67.28 mg/g at a temperature of 318 K, which was attributed to the presence of a large proportion of mesopores and abundant micropores simultaneously in carbon aerogels. Furthermore, with the interference of chlorinated solvents such as trichloroethylene (TCE), the removal efficiency of 1,4-dioxane had no obvious inhibition effect. Regeneration experiments showed that after five continuous cycles, the carbon aerogels still kept a comparable adsorption capacity, which illustrates its potential application in 1,4-dioxane-polluted water purification.

The global, regional, and national burden of foreign bodies from 1990 to 2019: a systematic analysis of the global burden of disease study 2019.

BACKGROUND: Foreign bodies (FBs) are a common emergency in medical institutions, that can occur in any area and among people of any age, which are common public health problems. Understanding the epidemiological characteristics of FBs is crucial for their prevention and control. The purpose of this study was to analyze the epidemiological characteristics of FBs worldwide through the data from the Global Burden of Disease Study 2019 (GBD 2019). METHODS: We obtained data from the GBD 2019, which is an important public database to understand the disease burden of FBs. Joinpoint was used to analyze temporal trends in the incidence and death trends of FBs, which is widely used to study the long-term temporal trend of the burden of diseases. SaTScan was used to detect spatial-temporal clusters of pulmonary aspiration and foreign body in the airway (PAFBA), which is based on a Poisson model, scanning the number of people and diseases in the study area to obtain the spatial-temporal clusters of diseases. RESULTS: Globally, the age-standardized incidence rate (ASIR) and the age-standardized death rate (ASDR) of FBs in 2019 were 869.23/100,000 (679.92/100,000-1120.69/100,000) and 1.55/100,000 (1.41/100,000-1.67/100,000), respectively. The ASIR and ASDR showed downtrends with average annual percent changes (AAPCs) of -0.31% and - 1.47% from 1990 to 2019. Of note, the ASIR showed an uptrend during 2010-2019, especially in high, high-middle, and middle SDI regions. Stratified analysis by age group showed that ASIR increased in each age group in recent years. From 1990 to 2019, the ASDR in the over-70 age group showed an uptrend worldwide, especially in high and high-middle SDI regions. In different types of FBs, the ASDR of PAFBA was the highest. The death burden of PAFBA was mainly clustered in 82 countries during 1993-2007, such as Canada, Cuba, and Mexico. CONCLUSION: The most important goal is to improve public awareness and emergency knowledge of FBs through publicity methods, such as the internet or offline activities, and to improve laws and regulations. Additionally, different age groups need different targeted measures, such as strengthening the care of children, caring for elderly individuals, improving necessary monitoring programs and reporting systems, conducting effective hazard assessments, and publicity and education activities.

The RNA m6A demethylase ALKBH5 drives emergency granulopoiesis and neutrophil mobilization by upregulating G-CSFR expression.

Emergency granulopoiesis and neutrophil mobilization that can be triggered by granulocyte colony-stimulating factor (G-CSF) through its receptor G-CSFR are essential for antibacterial innate defense. However, the epigenetic modifiers crucial for intrinsically regulating G-CSFR expression and the antibacterial response of neutrophils remain largely unclear. N6-methyladenosine (m6A) RNA modification and the related demethylase alkB homolog 5 (ALKBH5) are key epigenetic regulators of immunity and inflammation, but their roles in neutrophil production and mobilization are still unknown. We used cecal ligation and puncture (CLP)-induced polymicrobial sepsis to model systemic bacterial infection, and we report that ALKBH5 is required for emergency granulopoiesis and neutrophil mobilization. ALKBH5 depletion significantly impaired the production of immature neutrophils in the bone marrow of septic mice. In addition, Alkbh5-deficient septic mice exhibited higher retention of mature neutrophils in the bone marrow and defective neutrophil release into the circulation, which led to fewer neutrophils at the infection site than in their wild-type littermates. During bacterial infection, ALKBH5 imprinted production- and mobilization-promoting transcriptome signatures in both mouse and human neutrophils. Mechanistically, ALKBH5 erased m6A methylation on the CSF3R mRNA to increase the mRNA stability and protein expression of G-CSFR, consequently upregulating cell surface G-CSFR expression and downstream STAT3 signaling in neutrophils. The RIP-qPCR results confirmed the direct binding of ALKBH5 to the CSF3R mRNA, and the binding strength declined upon bacterial infection, accounting for the decrease in G-CSFR expression on bacteria-infected neutrophils. Considering these results collectively, we define a new role of ALKBH5 in intrinsically driving neutrophil production and mobilization through m6A demethylation-dependent posttranscriptional regulation, indicating that m6A RNA modification in neutrophils is a potential target for treating bacterial infections and neutropenia.

Ir/Zn-cocatalyzed chemo- and atroposelective [2+2+2] cycloaddition for construction of C─N axially chiral indoles and pyrroles.

Here, an Ir/Zn-cocatalyzed atroposelective [2+2+2] cycloaddition of 1,6-diynes and ynamines was developed, forging various functionalized C─N axially chiral indoles and pyrroles in generally good to excellent yields (up to 99%), excellent chemoselectivities, and high enantioselectivities (up to 98% enantiomeric excess) with wide substrate scope. This cocatalyzed strategy not only provided an alternative promising and reliable way for asymmetric alkyne [2+2+2] cyclotrimerization in an easy handle but also settled the issues of previous [Rh(COD)2]BF4-catalyzed system on the construction of C─N axial chirality such as complex operations, limited substrate scope, and low efficiency. In addition, control experiments and theoretical calculations disclosed that Zn(OTf)2 markedly reduced the barrier of migration insertion to significantly increase reaction efficiency, which was distinctly different from previous work on the Lewis acid for improving reaction yield through accelerating oxidative addition and reductive elimination.

Porphyrin Supramolecular Nanoassembly/C3N4 Nanosheet S-Scheme Heterojunctions for Selective Photocatalytic CO2 Reduction toward CO.

The photocatalytic reduction of CO2 with H2O into valuable chemicals is a sustainable carbon-neutral technology for renewable energy; however, the photocatalytic activity and product selectivity remain challenging. Herein, an S-scheme heterojunction photocatalyst with superior CO2 photoreduction performance─porous C3N4 (CN) nanosheets anchored with zinc(II) tetra(4-cyanophenyl)porphyrin (ZnTP) nanoassemblies (denoted as ZnTP/CN)─was designed and prepared via a simple self-assembly process. The constructed ZnTP/CN heterojunction had rich accessible active sites, improved CO2 absorption capacity, and high charge carrier separation efficiency caused by the S-scheme heterojunction. As a result, the obtained ZnTP/CN catalyst exhibited considerable activity for photocatalytic CO2 reduction, yielding CO with a generation rate of 19.4 µmol g-1·h-1 and a high selectivity of 95.8%, which is much higher than that of pristine CN nanosheets (4.53 µmol g-1·h-1, 57.4%). In addition, theoretical calculations and in situ Fourier transform infrared spectra demonstrated that the Zn sites in the porphyrin unit favor CO2 activation and *COOH formation as well as CO desorption, thereby affording a high CO selectivity. This work provides insight into the design and fabrication of efficient S-scheme heterostructure photocatalysts for solar energy storage.

Glycolytic metabolite phosphoenolpyruvate protects host from viral infection through promoting AATK expression.

Viral infections can result in metabolism rewiring of host cells, which in turn affects the viral lifecycle. Phosphoenolpyruvate (PEP), a metabolic intermediate in the glycolytic pathway, plays important roles in several biological processes including anti-tumor T cell immunity. However, whether PEP might participate in modulating viral infection remains largely unknown. Here, we demonstrate that PEP generally inhibits viral replication via upregulation of apoptosis-associated tyrosine kinase (AATK) expression. Targeted metabolomic analyses have shown that the intracellular level of PEP was increased upon viral infection. PEP treatment significantly restricted viral infection and hence declined subsequent inflammatory response both in vitro and in vivo. Besides, PEP took inhibitory effect on the stage of viral replication and also decreased the mortality of mice with viral infection. Mechanistically, PEP significantly promoted the expression of AATK. Knockdown of AATK led to enhanced viral replication and consequent increased levels of cytokines. Moreover, AATK deficiency disabled the antiviral effect of PEP. Together, our study reveals a previously unknown role of PEP in broadly inhibiting viral replication by promoting AATK expression, highlighting the potential application of activation or upregulation of the PEP-AATK axis in controlling viral infections.

Activation of glucagon-like peptide-1 receptor in microglia exerts protective effects against sepsis-induced encephalopathy via attenuating endoplasmic reticulum stress-associated inflammation and apoptosis in a mouse model of sepsis.

Sepsis-induced encephalopathy (SAE) is a detrimental complication in patients with severe sepsis, while there is still no effective treatment. Previous studies have elucidated the neuroprotective effects of glucagon-like peptide-1 receptor (GLP-1R) agonists. However, the role of GLP-1R agonists in the pathological process of SAE is unclear. Here, we found that GLP-1R was up-regulated in the microglia of septic mice. The activation of GLP-1R with Liraglutide could inhibit endoplasmic reticulum stress (ER stress) and associated inflammatory response as well as apoptosis triggered by LPS or tunicamycin (TM) in BV2 cells. In vivo experiments confirmed the benefits of Liraglutide in the regulation of microglial activation, ER stress, inflammation, and apoptosis in the hippocampus of septic mice. Additionally, the survival rate and cognitive dysfunction of septic mice were also improved after Liraglutide administration. Mechanically, cAMP/PKA/CREB signaling is involved in the protection of ER stress-induced inflammation and apoptosis in cultured microglial cells under LPS or TM stimulations. In conclusion, we speculated that GLP-1/GLP-1R activation in microglia might be a potential therapeutic target for the treatment of SAE.

Piezo-Activated Atomic-Thin Molybdenum Disulfide/MXene Nanoenzyme for Integrated and Efficient Tumor Therapy via Ultrasound-Triggered Schottky Electric Field.

Monolayer molybdenum disulfide (MoS2 ) nanoenzymes exhibit a piezoelectric polarization, which generates reactive oxygen species to inactivate tumors under ultrasonic strain. However, its therapeutic efficiency is far away from satisfactory, due to stackable MoS2 , quenching of piezo-generated charges, and monotherapy. Herein, chitosan-exfoliated monolayer MoS2 (Ch-MS) is composited with atomic-thin MXene, Ti3 C2 (TC), to self-assemble a multimodal nanoplatform, Ti3 C2 -Chitosan-MoS2 (TC@Ch-MS), for tumor inactivation. TC@Ch-MS not only inherits piezoelectricity from monolayer MoS2 , but also maintains remarkable stability. Intrinsic metallic MXene combines with MoS2 to construct an interfacial Schottky heterojunction, facilitating the separation of electron-hole pairs and endowing TC@Ch-MS increase-sensitivity magnetic resonance imaging responding. Schottky interface also leads to peroxidase mimetics with excellent catalytic performance toward H2 O2 in the tumor microenvironment under mechanical vibration. TC@Ch-MS possesses the superior photothermal conversion efficiency than pristine TC under near-infrared ray illumination, attributed to its enhanced interlaminar conductivity. Meanwhile, TC@Ch-MS realizes optimized efficiency on tumor apoptosis with immunotherapy. Therefore, TC@Ch-MS achieves an integrated diagnosis and multimodal treatment nanoplatform, whereas the toxicity to normal tissue cells is negligible. This work may shed fresh light on optimizing the piezoelectric materials in biological applications, and also give prominence to the significance of intrinsic metallicity in MXene.

Lung Resident Memory T Cells Activated by Oral Vaccination Afford Comprehensive Protection against Pneumonic Yersinia pestis Infection.

A growing body of evidence has shown that resident memory T (TRM) cells formed in tissue after mucosal infection or vaccination are crucial for counteracting reinfection by pathogens. However, whether lung TRM cells activated by oral immunization with Yptb1(pYA5199) play a protective role against pneumonic plague remains unclear. In this study, we demonstrated that lung CD4+ and CD8+ TRM cells significantly accumulated in the lungs of orally Yptb1(pYA5199)-vaccinated mice and dramatically expanded with elevated IL-17A, IFN-γ, and/or TNF-α production after pulmonary Yersinia pestis infection and afforded significant protection. Short-term or long-term treatment of immunized mice with FTY720 did not affect lung TRM cell formation and expansion or protection against pneumonic plague. Moreover, the intratracheal transfer of both lung CD4+ and CD8+ TRM cells conferred comprehensive protection against pneumonic plague in naive recipient mice. Lung TRM cell-mediated protection was dramatically abolished by the neutralization of both IFN-γ and IL-17A. Our findings reveal that lung TRM cells can be activated via oral Yptb1(pYA5199) vaccination, and that IL-17A and IFN-γ production play an essential role in adaptive immunity against pulmonary Y. pestis infection. This study highlights an important new target for developing an effective pneumonic plague vaccine.

Agglutination of Borreliella burgdorferi by Transmission-Blocking OspA Monoclonal Antibodies and Monovalent Fab Fragments.

Lyme disease vaccines based on recombinant Outer surface protein A (OspA) elicit protective antibodies that interfere with tick-to-host transmission of the disease-causing spirochete Borreliella burgdorferi. Another hallmark of OspA antisera and certain OspA monoclonal antibodies (MAbs) is their capacity to induce B. burgdorferi agglutination in vitro, a phenomenon first reported more than 30 years ago but never studied in molecular detail. In this report, we demonstrate that transmission-blocking OspA MAbs, individually and in combination, promote dose-dependent and epitope-specific agglutination of B. burgdorferi. Agglutination occurred within minutes and persisted for hours. Spirochetes in the core of the aggregates exhibited evidence of outer membrane (OM) stress, revealed by propidium iodide uptake. The most potent agglutinator was the mouse MAb LA-2, which targets the OspA C terminus (ß-strands 18 to 20). Human MAb 319-44, which also targets the OspA C terminus (ß-strand 20), and 857-2, which targets the OspA central ß-sheet (strands 8 to 10), were less potent agglutinators, while MAb 221-7, which targets ß-strands 10 to 11, had little to no measurable agglutinating activity, even though its affinity for OspA exceeded that of LA-2. Remarkably, monovalent Fab fragments derived from LA-2, and to a lesser degree 319-44, retained the capacity to induce B. burgdorferi aggregation and OM stress, a particularly intriguing observation considering that "LA-2-like" Fabs have been shown to experimentally entrap B. burgdorferi within infected ticks and prevent transmission during feeding to a mammalian host. It is therefore tempting to speculate that B. burgdorferi aggregation triggered by OspA-specific antibodies in vitro may in fact reflect an important biological activity in vivo.

Optimized acoustic streaming generated at oblique incident angles to improve ultrasound thrombolysis effect.

BACKGROUND: Combined with thrombolytic drugs and/or microbubbles, ultrasound (US) has been regarded as a useful tool for thrombolysis treatment by taking its advantages of noninvasive, non-ionization, low cost, and accurate targeting of tissues deep in body. Recently, low-intensity pulsed US, which can cause fewer complications by stable cavitation and acoustic streaming other than more violent effects, has attracted broad attention. PURPOSE: However, the thrombolysis effect in practice might not achieve expectation because there is not an ideal parallel multilayered structure between the skin and the targeted vessel. Therefore, the current work aims to better elucidate the influence of US incident angle on the generation of acoustic streaming and thrombolysis effect. METHODS: Systemic numerical and experimental studies, namely, finite element modeling (FEM), particle image velocimetry (PIV), and in vitro thrombolysis measurements, were performed to estimate the acoustical/streaming field pattern, maximum flow velocity, and shear stress on the surface of thrombus, as well as the lysis rate generated at different conditions. These methods aim at verifying the hypothesis that streaming-induced vortices can further accelerate the dissolution of the thrombus and optimized thrombolysis effected can be achieved by adjusting US incident angles. RESULTS: The pool data results showed that the variation trends of the flow velocity and shear stress obtained from FEM simulation and PIV experiments are qualitatively consistent with each other. There exists an optimal incident angle that can maximize the flow velocity and shear stress on the surface of thrombus, so that superior stirring and mixing effect can be generated. Furthermore, as the flow velocity and shear stress on thrombus surface are both highly correlated with the thrombolysis effect (the correlation coefficient R1 = 0.988, R2 = 0.958, respectively), the peak value of lysis rate (increase by at least 5.02%) also occurred at 10°. CONCLUSIONS: The current results demonstrated that, with appropriately determined incident angle, higher thrombolysis rate could be achieved without increasing the driving pressure. It may shed the light on future US thrombolysis planning strategy that, if combined with other advanced technologies (e.g., machine-learning-based image analysis and image-guided adaptive US emission modulation), more efficient thrombolytic effect could be realized while minimizing undesired side-effects caused by excessively high pressure.

m6A demethylase ALKBH5 is required for antibacterial innate defense by intrinsic motivation of neutrophil migration.

Neutrophil migration into the site of infection is necessary for antibacterial innate defense, whereas impaired neutrophil migration may result in excessive inflammation and even sepsis. The neutrophil migration directed by extracellular signals such as chemokines has been extensively studied, yet the intrinsic mechanism for determining neutrophil ability to migrate needs further investigation. N6-methyladenosine (m6A) RNA modification is important in immunity and inflammation, and our preliminary data indicate downregulation of RNA m6A demethylase alkB homolog 5 (ALKBH5) in neutrophils during bacterial infection. Whether m6A modification and ALKBH5 might intrinsically modulate neutrophil innate response remain unknown. Here we report that ALKBH5 is required for antibacterial innate defense by enhancing intrinsic ability of neutrophil migration. We found that deficiency of ALKBH5 increased mortality of mice with polymicrobial sepsis induced by cecal ligation and puncture (CLP), and Alkbh5-deficient CLP mice exhibited higher bacterial burden and massive proinflammatory cytokine production in the peritoneal cavity and blood because of less neutrophil migration. Alkbh5-deficient neutrophils had lower CXCR2 expression, thus exhibiting impaired migration toward chemokine CXCL2. Mechanistically, ALKBH5-mediated m6A demethylation empowered neutrophils with high migration capability through altering the RNA decay, consequently regulating protein expression of its targets, neutrophil migration-related molecules, including increased expression of neutrophil migration-promoting CXCR2 and NLRP12, but decreased expression of neutrophil migration-suppressive PTGER4, TNC, and WNK1. Our findings reveal a previously unknown role of ALKBH5 in imprinting migration-promoting transcriptome signatures in neutrophils and intrinsically promoting neutrophil migration for antibacterial defense, highlighting the potential application of targeting neutrophil m6A modification in controlling bacterial infections.

Diagnostic Value of Aortic Dissection Risk Score, Coagulation Function, and Laboratory Indexes in Acute Aortic Dissection.

Objective: This study was aimed at studying the diagnostic value of aortic dissection (AD) risk score, coagulation function, and laboratory indicators in acute aortic dissection (AAD). Methods: In this retrospective study, 57 patients with AAD and 57 with an acute coronary syndrome (ACS). During the same period, 50 healthy subjects were selected as the control group admitted to our institution which were assessed for eligibility and recruited. They were assigned to an AD group (AAD patients) and an ACS group (ACS patients). The AD risk scores, coagulation function indexes, and laboratory indexes of the two groups were compared. With digital subtraction angiography- (DSA-) based diagnosis result as the gold standard, the receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of various indexes for AD, and the sensitivity, specificity, and optimal diagnostic value (Youden index) of the diagnostic indexes were calculated. Additionally, the overall blood clot formation strength (MA), clotting factor function (R), platelet function (MAp), and functional fibrinogen (MAf) levels were evaluated. Results: AAD risk, AD screening, early diagnosis of AAD, fibrinogen degradation products (FDP), fibrinogen (Fib), prothrombin time (PT), activated partial thromboplastin time (APTT), tenascin C (TN-C), D-dimer (D-D), and N-terminal B-type natriuretic peptide precursor (NT-proBNP) in the three groups were statistically different (P < 0.05). Further pairwise comparisons showed that the AD patients got higher scores of AAD risk, AD screening, and early diagnosis of AAD versus ACS patients (P < 0.05). AD was associated with lower levels of fibrinogen degradation products (FDP) and fibrinogen (Fib), shorter prothrombin time (PT), and activated partial thromboplastin time (APTT) versus ACS (P < 0.05). AD also resulted in higher levels of tenascin C (TN-C), D-dimer (D-D), and N-terminal B-type natriuretic peptide precursor (NT-proBNP) versus ACS (P < 0.05). The three risk scores, various laboratory indicators, and various coagulation function indicators were of high diagnostic values for the diagnosis of AAD (AUC > 0.9, P < 0.05). The sensitivity of the AD screening scale and TN-C expression level to the diagnosis of AAD was up to 100%, and the specificity of TN-C expression level was up to 98.25%. The influencing factors of AAD included Fib, FDP, PT, APTT, D-D, TN-C, and NT-proBNP. MA, MAf, and MAp displayed the same trend and reached the lowest point at T2. R was the opposite and reached the highest point at T2. At T4, a higher Map and a lower MAf were found than before surgery, and R and MA returned to preoperative levels. The positive detection rate of ACS by CT scan was positively correlated with the degree of stenosis (r = 0.814, P < 0.05). Conclusion: AD screening scale, TN-C, and FDP are of the highest diagnostic value in the risk score of AD, laboratory indicators, and coagulation function. It has implications for the diagnosis of ADD.

A mouse model of exertional heatstroke-related acute kidney injury.

Background: Acute kidney injury (AKI) is a common complication of exertional heat stroke (EHS) with a complex pathogenesis. We established a stable mouse model of EHS-related AKI (EHS-AKI). Methods: C57BL/6 male mice were divided into 6 groups: Saline Control group, Glycerol Control group, Saline + Sham heat exercise (SHE) group, Saline + Heat exercise (HE) group, Glycerol + SHE group, and Glycerol + HE group. Samples from the Saline Control group and the Glycerol Control group were taken 6 h after the intramuscular injection of saline (4 mL/kg) or glycerol (4 mL/kg) to provide a baseline for comparisons with the other 4 groups. The other 4 groups of mice started exercise 6 h after the intramuscular injection of saline or glycerol, and were sacrificed to collect samples after exercise. Finally, serum and the pathology of kidney and muscle tissues were quantified. Results: There were no differences in the creatinine (Cr), blood urea nitrogen (BUN), creatine kinase (CK), and myoglobin (MYO) levels, but the interleukin 6 (IL-6) level was more increased (P<0.05) in the Glycerol Control group than the Saline Control group at the baseline. The IL-6 levels of the Glycerol + HE group were also higher than those of the Saline + HE groups at 6 and 12 h (P<0.05). The Cr levels at 12 h and 1 day, the BUN levels at 6 h, 12 h, 1 day, and 2 days in the Glycerol+ HE group were higher than the baseline levels (P<0.05). And the renal pathological scores at 6 h, 12 h, 1 day, 2 days, or 3 days were 0.79, 1.29, 1.58, 0.85, and 0.77. However, there was only slight renal pathological injury in the Saline + HE group at 12 h, and 1 day, and the scores were 0.13, and 0.41. The CK level in each group all peaked at 6 h after exercise and higher than the baseline (P<0.05). However, there was no difference in the MYO levels of each group compared to the baseline. Conclusions: We established a stable mouse model of EHS-AKI by conducting a heat exercise after the intramuscular injection of glycerol. Our findings lay the foundation for follow-up clinical and basic research.