The effect of fine grits and fine debris concentrations on the MLVSS/MLSS ratio of an activated sludge system.

This study embarks on an explorative investigation into the effects of typical concentrations and varying particle sizes of fine grits (FG, the involatile portion of suspended solids) and fine debris (FD, the volatile yet unbiodegradable fraction of suspended solids) within the influent on the mixed liquor volatile suspended solids (MLVSS)/mixed liquor suspended solids (MLSS) ratio of an activated sludge system. Through meticulous experimentation, it was discerned that the addition of FG or FD, the particle size of FG, and the concentration of FD bore no substantial impact on the pollutant removal efficiency (denoted by the removal rate of COD and ammonia nitrogen) under constant operational conditions. However, a notable decrease in the MLVSS/MLSS ratio was observed with a typical FG concentration of 20 mg/L, with smaller FG particle sizes exacerbating this reduction. Additionally, variations in FD concentrations influenced both MLSS and MLVSS/MLSS ratios; a higher FD concentration led to an increased MLSS and a reduced MLVSS/MLSS ratio, indicating FD accumulation in the system. A predictive model for MLVSS/MLSS was constructed based on quality balance calculations, offering a tool for foreseeing the MLVSS/MLSS ratio under stable long-term influent conditions of FG and FD. This model, validated using data from the BXH wastewater treatment plant (WWTP), showcased remarkable accuracy.

Single dose of intravenous miR199a-5p delivery targeting ischemic heart for long-term repair of myocardial infarction.

Long-term treatment of myocardial infarction is challenging despite medical advances. Tissue engineering shows promise for MI repair, but implantation complexity and uncertain outcomes pose obstacles. microRNAs regulate genes involved in apoptosis, angiogenesis, and myocardial contraction, making them valuable for long-term repair. In this study, we find downregulated miR-199a-5p expression in MI. Intramyocardial injection of miR-199a-5p into the infarcted region of male rats revealed its dual protective effects on the heart. Specifically, miR-199a-5p targets AGTR1, diminishing early oxidative damage post-myocardial infarction, and MARK4, which influences long-term myocardial contractility and enhances cardiac function. To deliver miR-199a-5p efficiently and specifically to ischemic myocardial tissue, we use CSTSMLKAC peptide to construct P-MSN/miR199a-5p nanoparticles. Intravenous administration of these nanoparticles reduces myocardial injury and protects cardiac function. Our findings demonstrate the effectiveness of P-MSN/miR199a-5p nanoparticles in repairing MI through enhanced contraction and anti-apoptosis. miR199a-5p holds significant therapeutic potential for long-term repair of myocardial infarction.

Predictors of outcome in large vessel occlusion stroke patients with intravenous tirofiban treatment: a post hoc analysis of the RESCUE BT clinical trial.

OBJECTIVE: The aim of this study was to investigate the factors influencing good outcomes in patients receiving only intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. METHODS: Post hoc exploratory analysis using the RESCUE BT trial identified consecutive patients who received intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke in 55 comprehensive stroke centers from October 2018 to January 2022 in China. RESULTS: A total of 521 patients received intravenous tirofiban, 253 of whom achieved a good 90-day outcome (modified Rankin Scale [mRS] 0-2). Younger age (adjusted odds ratio [aOR]: 0.965, 95% confidence interval [CI]: 0.947-0.982; p < 0.001), lower serum glucose (aOR: 0.865, 95%CI: 0.807-0.928; p < 0.001), lower baseline National Institutes of Health Stroke Scale (NIHSS) score (aOR: 0.907, 95%CI: 0.869-0.947; p < 0.001), fewer total passes (aOR: 0.791, 95%CI: 0.665-0.939; p = 0.008), shorter punctures to recanalization time (aOR: 0.995, 95%CI:0.991-0.999; p = 0.017), and modified Thrombolysis in Cerebral Infarction (mTICI) score 2b to 3 (aOR: 8.330, 95%CI: 2.705-25.653; p < 0.001) were independent predictors of good outcomes after intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. CONCLUSION: Younger age, lower serum glucose level, lower baseline NIHSS score, fewer total passes, shorter punctures to recanalization time, and mTICI scores of 2b to 3 were independent predictors of good outcomes after intravenous tirofiban with endovascular thrombectomy for large vessel occlusion stroke. CHINESE CLINICAL TRIAL REGISTRY IDENTIFIER: ChiCTR-IOR-17014167.

Exploring Protein Bioconjugation: A Redox-Based Strategy for Tryptophan Targeting.

Amino acid bioconjugation technology has emerged as a pivotal tool for linking small-molecule fragments with proteins, antibodies, and even cells. The study in Nature by Chang and Toste introduces a redox-based strategy for tryptophan bioconjugation, employing N-sulfonyloxaziridines as oxidative cyclization reagents, demonstrating high efficiency comparable to traditional click reactions. Meanwhile, this tool provides feasible methods for investigating the mechanisms underlying functional tryptophan-related biochemical processes, paving the way for protein function exploration, activity-based proteomics for functional amino acid identification and characterization, and even the design of covalent inhibitors.

Quenching and enhancement mechanisms of a novel Cd-based coordination polymer as a multiresponsive fluorescent sensor for nitrobenzene and aniline.

BACKGROUND: Nitroaromatic compounds are inherently hazardous and explosive, so convenient and rapid detection strategies are needed for the sake of human health and the environment. There is an urgent demand for chemical sensing materials that offer high sensitivity, operational simplicity, and recognizability to effectively monitor nitroaromatic residues in industrial wastewater. Despite its importance, the mechanisms underlying fluorescence quenching or enhancement in fluorescent sensing materials have not been extensively researched. The design and synthesis of multiresponsive fluorescent sensing materials have been a great challenge until now. RESULTS: In this study, a one-dimensional Cd-based fluorescent porous coordination polymer (Cd-CIP-1) was synthesized using 5-(4-cyanobenzyl)isophthalic acid (5-H2CIP) and 4,4'-bis(1-imidazolyl)biphenyl (4,4'-bimp) and used for the selective detection of nitrobenzene in aqueous solution by fluorescence quenching, with a limit of detection of 1.38 × 10-8 mol L-1. The presence of aniline in the Cd-CIP-1 solution leads to the enhancement of fluorescence property. Density functional theory and time-dependent density functional theory calculations were carried out to elucidate the mechanisms of the fluorescence changes. This study revealed that the specific pore size of Cd-CIP-1 facilitates analyte screening and enhances host-guest electron coupling. Furthermore, π-π interactions and hydrogen bond between Cd-CIP-1 and the analytes result in intermolecular orbital overlap and thereby boosting electron transfer efficiency. The different electron flow directions in NB@Cd-CIP-1 and ANI@Cd-CIP-1 lead to fluorescence quenching and enhancement. SIGNIFICANCE AND NOVELTY: The multiresponsive coordination polymer (Cd-CIP-1) can selectively detect nitrobenzene and recognize aniline in aqueous solutions. The mechanism of fluorescence quenching and enhancement has been thoroughly elucidated through a combination of density functional theory and experimental approaches. This study presents a promising strategy for the practical implementation of a multiresponsive fluorescent chemical sensor.

Fast and nondestructive discrimination of coal types based on spectral feature parameters.

Coal type identification is the basic work of coal quality inspection, which is of great significance to the normal operation of power generation, metallurgy, and other industries. The traditional coal-type identification method is complicated and requires comprehensive determination of various chemical parameters to obtain more accurate analysis results. Hyperspectral detection and analysis technology has the advantages of being simple, fast, nondestructive, and safe, and is widely used in a variety of fields. In this study, typical spectral feature parameters of coal samples were extracted based on hyperspectral data, and the parameters' sensitivity to coal types was explored using one-way ANOVA. The results showed that the coal spectral feature parameters of DI1-2µm and AD2.2µm significantly differed with coal species, indicating that the two parameters were class-sensitive features. When DI1-2µm and AD2.2µm were used to construct the Fisher discriminant model, the coal types could be discriminated with high accuracy. At the same time, the correlation between the extracted spectral feature parameters and the physicochemical parameters of bituminous coal and anthracite was analyzed. The results showed that there was a certain basis for using the extracted spectral feature parameters as the sensitive spectral characteristics of the model, and the application potential of the spectral characteristics of coal in the nondestructive prediction analysis of coal parameters was further discussed.

CALCR exacerbates renal cell carcinoma progression via stabilizing CD44.

The calcitonin receptor (CALCR) is an essential protein for maintaining calcium homeostasis and has been reported to be upregulated in numerous cancers. However, the molecular role of CALCR in renal cell carcinoma (RCC) is not well understood. In this study, we identified the overexpression of CALCR in RCC using human tissue chip by immunohistochemical (IHC) staining, which was associated with a poor prognosis. Functionally, CALCR depletion inhibited RCC cell proliferation and migration, and induced cell apoptosis and cycle arrest. CALCR is also essential for in vivo tumor formation. Mechanistically, we demonstrated that CALCR could directly bind to CD44, preventing CD44 protein degradation and thereby upregulating CD44 expression. Moreover, a deficiency in CD44 significantly attenuated the promoting role of CALCR on RCC cell proliferation, migration and anti-apoptosis capacities. Collectively, CALCR exacerbates RCC progression via stabilizing CD44, offering a fundamental basis for considering CALCR as a potential therapeutic target for RCC patients.

Seawater quality criteria derivation and ecological risk assessment for dichlorvos in China.

Dichlorvos (DDVP) is a widely used organophosphorus pesticide (OPP) that has been frequently detected in the marine environment of China. Water quality criteria (WQC) is however not available for this emergent pollutant in the marine environment, which hinders its ecological risk assessment. This study, therefore, screened toxicity values of DDVP and conducted toxicity tests on six marine species to supplement toxicity data. The WQC for DDVP was derived with the species sensitivity distribution (SSD) methodology, based on which the ecological risk of DDVP in the seawater of China was assessed. The results showed that the recommended short-term (SWQC) and long-term water quality criteria (LWQC) for DDVP were 1.47 and 0.0521 µg/L, respectively. Most marine waters of China showed low or negligible risk (HQ < 1, ORP < 2 %), whereas some estuarine waters warrant further concern due to higher risk. This study provides the scientific basis for seawater quality standard formulation and ecological risk management for DDVP.

Alpha 1,3 N-Acetylgalactosaminyl Transferase (GTA) Impairs Invasion Potential of Trophoblast Cells in Preeclampsia.

Preeclampsia (PE) is a pregnancy-specific disorder associated with shallow invasion of the trophoblast cells and insufficient remodeling of the uterine spiral artery. Protein glycosylation plays an important role in trophoblast cell invasion. However, the glycobiological mechanism of PE has not been fully elucidated. In the current study, employing the Lectin array, we found that soybean agglutinin (SBA), which recognizes the terminal N-acetylgalactosamine α1,3-galactose (GalNAc α1,3 Gal) glycotype, was significantly increased in placental trophoblast cells from PE patients compared with third-trimester pregnant controls. Upregulating the expression of the key enzyme α1,3 N-acetylgalactosaminyl transferase (GTA) promoted the biosynthesis of terminal GalNAc α1,3 Gal and inhibited the migration/invasion of HTR8/SVneo trophoblast cells. Moreover, the methylation status of GTA promoter in placental tissues from PE patients was lower than that in the third trimester by methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) analysis. Elevated GTA expression in combination with the DNA methylation inhibitor 5-azacytidine (5-AzaC) treatment increased the glycotype biosynthesis and impaired the invasion potential of trophoblast cells, leading to preeclampsia. This study suggests that elevated terminal GalNAc α1,3 Gal biosynthesis and GTA expression may be applied as the new markers for evaluating placental function and the auxiliary diagnosis of preeclampsia.

Radical Deoxygenative Three-Component Reaction of Alcohols, Aryl Alkenes, and Cyanopyridines.

We report herein a deoxygenative radical multicomponent reaction involving alcohols, aryl alkenes, and cyanopyridine under photoredox conditions. This method is photoredox-neutral, suitable for late-stage modification, and compatible with a wide array of alcohols as alkyl radical sources, including primary, secondary, and tertiary alcohols. This reaction comprises a radical relay mechanism encompassing the Giese addition of aryl alkenes by alkyl radicals, followed by the decyanative pyridination of benzyl radicals.

A 2D nanoflower-like ordered mesoporous Bi12ZnO20 catalyst with excellent photocatalytic antibacterial properties.

The ordered mesoporous ZnO was successfully synthesized using the template method in this article, and Bi ions were etched into ZnO to form two-dimensional nanoflower structures of Bi12ZnO20 with NA3SSA as a guiding agent. The crystal structure, morphology, and optical properties of the photocatalyst were characterized by X-ray diffractometer (XRD), scanning electron microscope (SEM), energy-dispersive spectrometer(EDS), and ultraviolet-visible diffuse reflectance spectrum (UV-vis DRS). Under illumination conditions, the obtained materials exhibited excellent bactericidal ability against both gram-positive and gram-negative bacteria, as well as effective inhibition against fungi. Among them, the bactericidal effect of Pseudomonas aeruginosa was found to be the most rapid, achieving a sterilization rate of 100% within 30 min of light irradiation. Even after three cycles of antibacterial activity testing, the Bi12ZnO20 material still demonstrated good photocatalytic performance. The nanoflower-shaped materials provide an enhanced fluid adsorption capacity and more active centers for photocatalytic reactions while also improving light absorption capacity, photogenerated electron-hole separation efficiency, and electron transport efficiency. The cytotoxicity assessment of Bi12ZnO20 revealed no significant toxic effects. Therefore, this study presents a nanoflower-shaped material with highly efficient photocatalytic antibacterial properties for applications in production and daily life; it holds significant importance in eliminating harmful bacteria and plays a crucial role in environmental protection. IMPORTANCE: The flower-shaped photocatalytic material Bi12ZnO20, consisting of nanoparticles, was successfully synthesized in this study. Rigorous antibacterial experiments were conducted on various fungi using the material, yielding excellent results. Furthermore, the application of this material for antibacterial treatment of livestock and poultry manure sewage in real-life scenarios demonstrated remarkable efficacy.

[Clinical treatment and prognosis of adrenocortical carcinoma with venous tumor thrombus].

OBJECTIVE: To analyze the clinicopathological features, prognostic value and surgical treatment experience in patients with adrenocortical carcinoma with venous tumor thrombus. METHODS: We collected relevant data of the patients with adrenocortical carcinoma who had undergone surgery in Peking University Third Hospital from 2018 to 2023. The patients were divided into venous tumor thrombus group and non-tumor thrombus group. The Wilcoxon rank sum test was used to compare the quantitative variables. The chi-squared test and Fisher's exact test were used to compare the categorical variables. The Kaplan-Meier method was used to estimate the survival rate. RESULTS: A total of 27 patients with adrenocortical carcinoma were included, of whom 11 cases (40.7%) had venous tumor thrombus. In the patients with venous tumor thrombus, 8 patients were female and 3 were male. The median age was 49 (36, 58) years. The median body mass index was 26.0 (24.1, 30.4) kg/m2. Seven patients presented with symptoms at their initial visit. Six patients had a history of hypertension. Elevated levels of cortisol were observed in 2 cases. Three tumors were found on the left side, while 8 were found on the right side. Median tumor diameter was 9.4 (6.5, 12.5) cm. On the left, there was a case of tumor thrombus limited to the central vein of the left adrenal gland without invasion into the left renal vein, and two cases of tumor thrombus growth extending into the inferior vena cava below the liver. One case of tumor thrombus on the right adrenal central vein did not invade the inferior vena cava. Four cases of tumor thrombus invaded the inferior vena cava below the liver and three cases extended to the posterior of the liver. Ten patients were in European Network for the Study of Adrenal Tumors (ENSAT) stage Ⅲ and one was in ENSAT stage Ⅳ. Open surgery was performed in 6 cases, laparoscopic surgery alone in 4 cases and robot-assisted laparoscopic surgery in 1 case. Two patients underwent ipsilateral kidney resection. Median operative time was 332 (261, 440) min. Median intraoperative bleeding was 900 (700, 2 200) mL. Median hospital stay was 9 (5, 10) days. Median survival time for the patients with tumor thrombus was 24.0 months and median time to recurrence was 7.0 months. The median survival and recurrence time of 16 patients without tumor thrombus were not reached. The patients with tumor thrombus had worse 3-year overall survival (OS) rate (40.9% vs. 71.4%; Log-rank, P=0.038) and 2-year recurrence-free survival (RFS) (9.1% vs.53.7%; Log-rank, P=0.015) rates compared with the patients with non-tumor thrombus. CONCLUSION: Patients with adrenocortical carcinoma with venous tumor thrombus have poor prognosis. Different adrenal tumor resections and venous tumor thrombus removal procedures based on different tumor thrombus locations are safe and effective in treating this disease.

Machine learning for high-precision simulation of dissolved organic matter in sewer: Overcoming data restrictions with generative adversarial networks.

Understanding the transformation process of dissolved organic matter (DOM) in the sewer is imperative for comprehending material circulation and energy flow within the sewer. The machine learning (ML) model provides a feasible way to comprehend and simulate the DOM transformation process in the sewer. In contrast, the model accuracy is limited by data restriction. In this study, a novel framework by integrating generative adversarial network algorithm-machine learning models (GAN-ML) was established to overcome the drawbacks caused by the data restriction in the simulation of the DOM transformation process, and humification index (HIX) was selected as the output variable to evaluate the model performance. Results indicate that the GAN algorithm's virtual dataset could generally enhance the simulation performance of regression models, deep learning models, and ensemble models for the DOM transformation process. The highest prediction accuracy on HIX (R2 of 0.5389 and RMSE of 0.0273) was achieved by the adaptive boosting model which belongs to ensemble models trained by the virtual dataset of 1000 samples. Interpretability analysis revealed that dissolved oxygen (DO) and pH emerge as critical factors warranting attention for the future development of management strategies to regulate the DOM transformation process in sewers. The integrated framework proposed a potential approach for the comprehensive understanding and high-precision simulation of the DOM transformation process, paving the way for advancing sewer management strategy under data restriction.

Reformulating lipid nanoparticles for organ-targeted mRNA accumulation and translation.

Fully targeted mRNA therapeutics necessitate simultaneous organ-specific accumulation and effective translation. Despite some progress, delivery systems are still unable to fully achieve this. Here, we reformulate lipid nanoparticles (LNPs) through adjustments in lipid material structures and compositions to systematically achieve the pulmonary and hepatic (respectively) targeted mRNA distribution and expression. A combinatorial library of degradable-core based ionizable cationic lipids is designed, following by optimisation of LNP compositions. Contrary to current LNP paradigms, our findings demonstrate that cholesterol and phospholipid are dispensable for LNP functionality. Specifically, cholesterol-removal addresses the persistent challenge of preventing nanoparticle accumulation in hepatic tissues. By modulating and simplifying intrinsic LNP components, concurrent mRNA accumulation and translation is achieved in the lung and liver, respectively. This targeting strategy is applicable to existing LNP systems with potential to expand the progress of precise mRNA therapy for diverse diseases.

LanCL1 protects developing neurons from long-term isoflurane anesthesia-induced neurotoxicity.

Research has revealed that prolonged or repeated exposure to isoflurane, a common general anesthetic, can lead to cognitive and behavioral deficiencies, particularly in early life. The brain contains a wealth of LanCL1, an antioxidant enzyme that is thought to mitigate oxidative stress. Nevertheless, its precise function in mammals remains uncertain. This study uncovered a decrease in the expression of LanCL1 due to prolonged isoflurane anesthesia, accompanied by anesthesia-induced neurotoxicity in vivo and in vitro. To better understand LanCL1's essential function, LanCL1 overexpressing adenoviruses were employed to increase LanCL1 levels. The outcomes were analyzed using western blot and immunofluorescence methods. According to the findings, extended exposure to isoflurane anesthesia may lead to developmental neurotoxicity in vivo and in vitro. The anesthesia-induced neurotoxicity was concomitant with a reduction in LanCL1 expression. Moreover, the study revealed that overexpression of LanCL1 can mitigate the neurotoxic effects of isoflurane anesthesia, resulting in improved synaptic growth, less reactive oxygen species enhanced cell viability and rescued memory deficits in the developing brain. In conclusion, prolonged anesthesia-induced LanCL1 deficiency could be responsible for neurotoxicity and subsequent cognitive impairments in the developing brain. Additional LanCL1 counteracts this neurotoxic effect and protects neurons from long-term isoflurane anesthesia.

Establishment and verification of a predictive model for bone metastasis in patients with non-small cell lung cancer based on peripheral blood CX3CL and CCL28.

To establish a predictive model of bone metastasis in patients with non-small cell lung cancer (NSCLC) using peripheral blood CX3CL and CCL28, and to verify its application value. We retrospectively gathered clinical data from 210 patients with NSCLC treated at our institution between April 2021 and December 2023. These patients were stratified into two groups based on the presence of bone metastases: a bone metastasis group (n = 49) and a non-bone metastasis group (n = 161). A logistic regression model was developed to predict bone metastasis and to evaluate the model's predictive performance. Multivariate logistic regression analysis identified age (OR = 6.689, P < 0.001), carcinoembryonic antigen (CEA, OR = 5.699, P < 0.001), CX3CL1 (OR = 5.418, P < 0.001), and CCL28 (OR = 7.692, P < 0.001) as independent predictors of bone metastasis in NSCLC patients. The receiver operating characteristic (ROC) curve analysis yielded an area under the curve (AUC) of 0.794 for both the modeling and validation cohorts. Decision curve analysis (DCA) indicated a superior net benefit of the model. Calibration curves confirmed close concordance between predicted and observed probabilities of bone metastasis. The Hosmer-Lemeshow test yielded a chi-square statistic of 4.743 with a P-value of 0.178, suggesting a good fit. The predictive model utilizing serum levels of CX3CL1 and CCL28 demonstrates robust predictive accuracy and efficacy for bone metastasis in patients with NSCLC.

Revealing oxygen effect on efficiency and stability of quantum dot photovoltaics.

Colloidal quantum dot solar cells (CQDSCs) have received great attention in the development of scalable and stable photovoltaic devices. Despite the high power-conversion-efficiency (PCE) reported, stability investigations are still limited and the exact degradation mechanisms of CQDSCs remain unclear under different atmosphere conditions. In this study, the atmospheric influence on the ZnO electron transport layer material (ETL), halide-passivated lead sulfide CQDs (PbS-PbI2) photoactive layer material and 1,2-ethanedithiol-PbS CQDs (PbS-EDT) hole transport material on device stability in PbS CQDSCs is investigated. It was found that O2 had negligible influence on PbS-PbI2, but it did induce the increase in work function of ZnO ETL and PbS-EDT layers. Notably, the increase of the ZnO work function (WFZnO) induces the formation of interface barrier between ZnO and PbS-PbI2, leading to a deterioration in device efficiency. By further replacing ZnO ETL with SnO2, a multi-interface collaborative CQDSC was constructed to realize the PCE with high stability. This study identifies the efficiency evolution that is inherent in CQDSCs under different atmospheric conditions.

The Bifidobacterium-dominated fecal microbiome in dairy calves shapes the characteristic growth phenotype of host.

The dominant bacteria in the hindgut of calves play an important role in their growth and health, which could even lead to lifelong consequences. However, the identification of core probiotics in the hindgut and its mechanism regulating host growth remain unclear. Here, a total of 1045 fecal samples were analyzed by 16S rRNA gene sequencing from the 408 Holstein dairy calves at the age of 0, 14, 28, 42, 56, and 70 days to characterize the dynamic changes of core taxa. Moreover, the mechanisms of nutrient metabolism of calf growth regulated by core bacteria were investigated using multi-omics analyses. Finally, fecal microbiota transplantation (FMT) in mice were conducted to illustrate the potential beneficial effects of core bacteria. Four calf enterotypes were identified and enterotypes dominated by Bifidobacterium and Oscillospiraceae_UCG-005 were representative. The frequency of enterotype conversion shifted from variable to stable. The close relationship observed between phenotype and enterotype, revealing a potential pro-growth effect of Bifidobacterium, might be implemented by promoting the use of carbohydrate, activating the synthesis of volatile fatty acids, amino acids and vitamin B6, and inhibiting methane production in the hindgut. The FMT results indicated the beneficial effect of Bifidobacterium on host growth and hindgut development. These results support the notion that the Bifidobacterium-dominated fecal microbiome would be an important driving force for promoting the host growth in the early life. Our findings provide new insights into the potential probiotic mining and application strategies to promote the growth of young animals or improve their growth retardation.

PI3Kgamma promotes neutrophil extracellular trap formation by noncanonical pyroptosis in abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is one of the most life-threatening cardiovascular diseases; however, effective drug treatments are still lacking. The formation of neutrophil extracellular traps (NETs) has been shown to be crucial trigger of AAA and identifying upstream regulatory targets is thus key to discovering therapeutic agents for AAA. We revealed that phosphoinositide 3-kinase gamma (PI3Kγ) acted as an upstream regulatory molecule, and that PI3Kγ inhibition reduced NET formation and aortic wall inflammation, thereby markedly ameliorating AAA. However, the mechanism of NET formation regulated by PI3Kγ remains unclear. In this study, we showed that PI3Kγ deficiency inactivated the noncanonical pyroptosis pathway, which suppressed downstream NET formation. In addition, PI3Kγ regulation of noncanonical pyroptosis was dependent on cAMP/protein kinase A (cAMP/PKA) signaling. These results clarify the molecular mechanism and crosstalk between PI3Kγ and NETosis in the development of AAA, potentially facilitating the discovery of therapeutic options for AAA.

High Q-factor Polymer Microring Resonators Realized by Versatile Damascene Soft Nanoimprinting Lithography.

High-quality-factor microring resonators are highly desirable in many applications. Fabricating a microring resonator typically requires delicate instruments to ensure a smooth side wall of waveguides and 100-nm critical feature size in the coupling region. In this work, we demonstrate a new method "damascene soft nanoimprinting lithography" that can create high-fidelity waveguide by simply backfill an imprinted cladding template with a high refractive index polymer core. This method can easily realize high Q-factor polymer microring resonators (e.g., ~5 x 105 around 770 nm wavelength) without the use of any expensive instruments and can be conducted in a normal lab environment. The high Q-factors can be attributed to the residual layer-free feature and controllable meniscus cross-section profile of the filled polymer core. Furthermore, the new method is compatible with different polymers, yields low fabrication defects, enables new functionalities, and allows flexible substrate. These benefits can broaden the applicability of the fabricated microring resonator.