Grouting technique-combining transvenous Onyx and coils for the embolization of complex non-cavernous intracranial dural arteriovenous fistulas.

Objective: Incomplete occlusion of cerebral dural arteriovenous fistula (DAVF) may lead to fistula recurrence and rebleeding, which may necessitate several embolizations and lead to worse clinical outcomes. Herein, we describe a grouting technique for endovascular embolization and its outcomes in a series of patients with complex intracranial DAVF. Methods: A total of 20 patients with aggressive type or symptomatic intracranial non-cavernous DAVF underwent endovascular transvenous embolization combining detachable coils and Onyx. Two microcatheters were positioned either in the distal segment of the involved sinus or near the draining veins. To achieve tight occlusion of the involved sinus, coils were carefully delivered through the first microcatheter, starting from the distal segment and then to the proximal segment. Next, Onyx was injected through the second microcatheter to reinforce and fill (grout) the interspace of coil mass and gradually refluxed to the mural channels and para-sinus cortical veins until the fistula was completely occluded. Results: Successful embolization was achieved in all 20 patients. The initial angiographic results revealed the achievement of complete occlusion in 19 patients (95%). At the postembolization follow-up, complete obliteration of the fistula was achieved in all patients (100%). No symptom or angiographic recurrence was observed at the 2- to 5-year follow-ups. No patient required additional embolization or stereotactic radiosurgery. Conclusion: The proposed grouting technique combining detachable coils and Onyx appears to be promising for the elimination of complex intracranial non-cavernous DAVFs.

Flux synthesis of two-dimensional covalent organic frameworks.

Covalent organic frameworks (COFs) are crystalline porous polymers constructed from organic building blocks into ordered two- or three-dimensional networks through dynamic covalent bonds. Attributed to their high porosity, well-defined structure, tailored functionality and excellent chemical stability, COFs have been considered ideal sorbents for various separation applications. The synthesis of COFs mainly employs the solvothermal method, which usually requires organic solvents in sealed Pyrex tubes, resulting in unscalable powdery products and environmental pollution that seriously limits their practical applications. Herein, our protocol focuses on an emerging synthesis method for COFs based on organic flux synthesis without adding solvents. The generality of this synthesis protocol has been applied in preparing various types of COFs, including olefin-linked, imide-linked, Schiff-based COFs on both gram and kilogram scales. Furthermore, organic flux synthesis avoids the disadvantages of solvothermal synthesis and enhances the crystallization and porosity of COFs. Typically, COF synthesis takes 3-5 d to complete, and subsequent washing procedures leading to pure COFs need 1 d. The procedure for kilogram-scale production of COFs with commercially available monomers is also provided. The resulting COFs are suitable for separation applications, particularly as adsorbent materials for industrial gas separation and water treatment applications. The protocol is suited for users with prior expertise in the synthesis of inorganic materials and porous organic materials.

Three-dimensional inertial focusing based impedance cytometer enabling high-accuracy characterization of electrical properties of tumor cells.

The differences in the cross-sectional positions of cells in the detection area have a severe negative impact on achieving accurate characterization of the impedance spectra of cells. Herein, we proposed a three-dimensional (3D) inertial focusing based impedance cytometer integrating sheath fluid compression and inertial focusing for the high-accuracy electrical characterization and identification of tumor cells. First, we studied the effects of the particle initial position and the sheath fluid compression on particle focusing. Then, the relationship of the particle height and the signal-to-noise ratio (SNR) of the impedance signal was explored. The results showed that efficient single-line focusing of 7-20 µm particles close to the electrodes was achieved and impedance signals with a high SNR and a low coefficient of variation (CV) were obtained. Finally, the electrical properties of three types of tumor cells (A549, MDA-MB-231, and UM-UC-3 cells) were accurately characterized. Machine learning algorithms were implemented to accurately identify tumor cells based on the amplitude and phase opacities at multiple frequencies. Compared with traditional two-dimensional (2D) inertial focusing, the identification accuracy of A549, MDA-MB-231, and UM-UC-3 cells using our 3D inertial focusing increased by 57.5%, 36.4% and 36.6%, respectively. The impedance cytometer enables the detection of cells with a wide size range without causing clogging and obtains high SNR signals, improving applicability to different complex biological samples and cell identification accuracy.

Reinforcing thermostability and pH robustness of exo-inulinase facilitated by ReverseTag/ReverseCatcher tagging system.

Enhancing protein stability is pivotal in the field of protein engineering. Protein self-cyclization using peptide a tagging system has emerged as an effective strategy for augmenting the thermostability of target proteins. In this study, we utilized a novel peptide tagging system, ReverseTag/ReverseCatcher, which leverages intramolecular ester bond formation. Initially, we employed GFP as a model to validate the feasibility of cyclization mediated by ReverseTag/ReverseCatcher in improving the protein thermostability. Cyclized GFP (cGFP) retained 30 % of its relative fluorescence after a 30-min incubation at 100 °C, while both GFP and linear GFP (lGFP) completely lost their fluorescence within 5 min. Additionally, we applied this method to exo-inulinase (EXINU), resulting in a variant named cyclized EXINU (cEXINU). The T50 and t1/2 values of cEXINU exhibited significant enhancements of 10 °C and 10 min, respectively, compared to EXINU. Furthermore, post-cyclization, EXINU demonstrated a broad operational pH range from 5 to 10 with sustained catalytic activity, and cEXINU maintained a half-life of 960 min at pH 5 and 9. Molecular dynamics simulations were conducted to elucidate the mechanisms underlying the enhanced thermostability and pH robustness of EXINU following cyclization. This study highlights that cyclization substanitially enhances the stability of both highly stable protein GFP and low-stable protein EXINU, mediated by the ReverseTag/ReverseCatcher tagging system. The ReverseTag/ReverseCatcher tagging system proves to be a potent conjugation method, with potential applications in improving thermostability, pH robustness, and other areas of protein engineering.

Electron Transporting Polymeric Materials with Partial Quaternization for High-Performance Organic Solar Cells.

Efficient cathode interfacial layers (CILs) have become a crucial component of organic solar cells (OSCs). Charge extraction barriers, interfacial trap states, and significant transport resistance may be induced due to the unfavorable cathode interlayer, limiting the device performance. In this study, poly(4-vinylpyridine) is used as the CIL for OSCs, and a new type of CIL named P4VP-I is synthesized through the quaternization strategy. Compared to P4VP, P4VP-I CIL exhibits enhanced conductivity and optimized work function. OSCs employing the P4VP-I ETL demonstrate prolonged carrier lifetime, suppressed charge recombination, and achieve higher power conversion efficiencies (PCE) than the commonly used ETLs such as PFN-Br and Phen-NaDPO.

Short-chain fatty acid butyrate against TMAO activating endoplasmic-reticulum stress and PERK/IRE1-axis with reducing atrial arrhythmia.

INTRODUCTION: The accumulation of microbiota-derived trimethylamine N-oxide (TMAO) in the atrium is linked to the development and progression of atrial arrhythmia. Butyrate, a major short-chain fatty acid, plays a crucial role in sustaining intestinal homeostasis and alleviating systemic inflammation, which may reduce atrial arrhythmogenesis. OBJECTIVES: This study explored the roles of butyrate in regulating TMAO-mediated atrial remodeling and arrhythmia. METHODS: Whole-cell patch clamp experiments, Western blotting, and immunocytochemistry were used to analyze electrical activity and signaling, respectively, in TMAO-treated HL-1 atrial myocytes with or without sodium butyrate (SB) administration. Telemetry electrocardiographic recording and echocardiography and Masson's trichrome staining and immunohistochemistry were employed to examine atrial function and histopathology, respectively, in mice treated with TMAO with and without SB administration. RESULTS: Compared with control cells, TMAO-treated HL-1 myocytes exhibited reduced action potential duration (APD), elevated sarcoplasmic reticulum (SR) calcium content, larger L-type calcium current (ICa-L), increased Na+/Ca2+ exchanger (NCX) current, and increased potassium current. However, the combination of SB and TMAO resulted in similar APD, SR calcium content, ICa-L, transient outward potassium current (Ito), and ultrarapid delayed rectifier potassium current (IKur) compared with controls. Additionally, TMAO-treated HL-1 myocytes exhibited increased activation of endoplasmic reticulum (ER) stress signaling, along with increased PKR-like ER stress kinase (PERK)/IRE1α axis activation and expression of phospho-IP3R, NCX, and Kv1.5, compared with controls or HL-1 cells treated with the combination of TMAO and SB. TMAO-treated mice exhibited atrial ectopic beats, impaired atrial function, increased atrial fibrosis, and greater activation of ER stress signaling with PERK/IRE1α axis activation compared with controls and mice treated with TMAO combined with SB. CONCLUSION: TMAO administration led to PERK/IRE1α axis activation, which may increase atrial remodeling and arrhythmogenesis. SB treatment mitigated TMAO-elicited ER stress. This finding suggests that SB administration is a valuable strategy for treating TMAO-induced atrial arrhythmia.

Isolation of Homogeneous Sub-populations of Spermatocytes from Mouse Testis.

Mammalian meiosis is a highly specialized cell division process, resulting in the production of genetically unique haploid cells. However, the molecular mechanisms governing meiosis remain largely unknown, primarily due to the difficulty in isolating pure sub-populations of spermatocytes. Definitive molecular, biochemical, and functional investigations of the meiosis process require the isolation of these individual homogeneous sub-populations of spermatocytes. Here, we present an approach that enables the purification of homogeneous spermatocytes from mouse testis at desired sub-stages. This approach consists of two strategic steps. The first is to synchronize spermatogenesis, aiming to minimize the diversity and complexity of testicular germ cells. The second involves utilizing mouse models with germ cell-specific fluorescent markers to differentiate the desired subtype from other cells in the testis. By employing fluorescence-activated cell sorting (FACS), this approach yields highly pure populations of spermatocytes at each sub-stage. When combined with other massively parallel sequencing techniques and in vitro cell culture methods, this approach will enhance our comprehension of the molecular mechanisms underlying mammalian meiosis and promote in vitro gametogenesis.

A worldwide study of white matter microstructural alterations in people living with Parkinson's disease.

The progression of Parkinson's disease (PD) is associated with microstructural alterations in neural pathways, contributing to both motor and cognitive decline. However, conflicting findings have emerged due to the use of heterogeneous methods in small studies. Here we performed a large diffusion MRI study in PD, integrating data from 17 cohorts worldwide, to identify stage-specific profiles of white matter differences. Diffusion-weighted MRI data from 1654 participants diagnosed with PD (age: 20-89 years; 33% female) and 885 controls (age: 19-84 years; 47% female) were analyzed using the ENIGMA-DTI protocol to evaluate white matter microstructure. Skeletonized maps of fractional anisotropy (FA) and mean diffusivity (MD) were compared across Hoehn and Yahr (HY) disease groups and controls to reveal the profile of white matter alterations at different stages. We found an enhanced, more widespread pattern of microstructural alterations with each stage of PD, with eventually lower FA and higher MD in almost all regions of interest: Cohen's d effect sizes reached d = -1.01 for FA differences in the fornix at PD HY Stage 4/5. The early PD signature in HY stage 1 included higher FA and lower MD across the entire white matter skeleton, in a direction opposite to that typical of other neurodegenerative diseases. FA and MD were associated with motor and non-motor clinical dysfunction. While overridden by degenerative changes in the later stages of PD, early PD is associated with paradoxically higher FA and lower MD in PD, consistent with early compensatory changes associated with the disorder.

Coupling Nanoscale Precision with Multiscale Imaging: A Multifunctional Near-Infrared Dye for the Brain.

Live imaging of primary neural cells is crucial for monitoring neuronal activity, especially multiscale and multifunctional imaging that offers excellent biocompatibility. Multiscale imaging can provide insights into cellular structure and function from the nanoscale to the millimeter scale. Multifunctional imaging can monitor different activities in the brain. However, this remains a challenge because of the lack of dyes with a high signal-to-background ratio, water solubility, and multiscale and multifunctional imaging capabilities. In this study, we present a neural dye with near-infrared (NIR) emissions (>700 nm) that enables ultrafast staining (in less than 1 min) for the imaging of primary neurons. This dye not only enables multiscale neural live-cell imaging from vesicles in neurites, neural membranes, and single neurons to the whole brain but also facilitates multifunctional imaging, such as the monitoring and quantifying of synaptic vesicles and the changes in membrane potential. We also explore the potential of this NIR neural dye for staining brain slices and live brains. The NIR neural dye exhibits superior binding with neural membranes compared to commercial dyes, thereby achieving multiscale and multifunctional brain neuroimaging. In conclusion, our findings introduce a significant breakthrough in neuroimaging dyes by developing a category of small molecular dyes.

Huanglian Jiedu decoction alleviates ischemia-induced cerebral injury in rats by mitigating NET formation and activiting GABAergic synapses.

Huanglian Jiedu decoction (HLJD) has been used to treat ischemic stroke in clinic. However, the detailed protective mechanisms of HLJD on ischemic stroke have yet to be elucidated. The aim of this study is to elucidate the underlying pharmacological mechanisms of HLJD based on the inhibition of neuroinflammation and the amelioration of nerve cell damage. A middle cerebral artery occlusion reperfusion (MCAO/R) model was established in rats and received HLJD treatment. Effects of HLJD on neurological function was assessed based on Bederson's score, postural reflex test and asymmetry score. 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining, Hematein and eosin (HE) and Nissl staining were used to observe the pathological changes in brain. Then, transcriptomics was used to screen the differential genes in brain tissue in MCAO/R model rats following HLJD intervention. Subsequently, the effects of HLJD on neutrophil extracellular trap (NET) formation-related neuroinflammation, gamma-aminobutyric acid (GABA)ergic synapse activation, nerve cell damage and proliferation were validated using immunofluorescence, western blot and enzyme-linked immunosorbent assay (ELISA). Our results showed that HLJD intervention reduced the Bederson's score, postural reflex test score and asymmetry score in MCAO/R model rats. Pathological staining indicated that HLJD treatment decreased the cerebral infarction area, mitigated neuronal damage and increased the numbers of Nissl bodies. Transcriptomics suggested that HLJD affected 435 genes in MCAO/R rats. Among them, several genes involving in NET formation and GABAergic synapses pathways were dysregulated. Subsequent experimental validation showed that HLJD reduced the MPO+CitH3+ positive expression area, reduced the protein expression of PAD4, p-P38/P38, p-ERK/ERK and decreased the levels of IL-1ß, IL-6 and TNF-α, reversed the increase of Iba1+TLR4+, Iba1+p65+ and Iba1+NLRP3+ positive expression area in brain. Moreover, HLJD increased GABA levels, elevated the protein expression of GABRG1 and GAT3, decreased the TUNEL positive expression area and increased the Ki67 positive expression area in brain. HLJD intervention exerts a multifaceted positive impact on ischemia-induced cerebral injury in MCAO/R rats. This intervention effectively inhibits neuroinflammation by mitigating NET formation, and concurrently improves nerve cell damage and fosters nerve cell proliferation through activating GABAergic synapses.

Identifying prognostic predictors for postoperative pituitary neuroendocrine tumour recurrence: an integrated clinical, radiological, and immunohistochemistry assessment.

OBJECTIVE: Pituitary neuroendocrine tumours (PitNETs) are the second most common type of intracranial tumour. Several studies have explored the prognostic factors for PitNETs. However, prognostic factors for postoperative PitNET recurrence remain not fully understood. This study aimed to explore potential prognostic factors for PitNET recurrence, such as surrounding tissue invasion and the extent of surgical resection in patients with postoperative PitNETs. METHODS: We included 106 patients who underwent PitNET surgery between 2013 and 2018, dividing them into two groups: those with recurrence and those without recurrence. Tumours were classified based on demographics, neuroradiological, and immunohistological characteristics. Univariate and multivariate analyses were used to determine factors predicting recurrence. Kaplan-Meier plots and log-rank tests were used to analyse each independent factor based on the cumulative 5-year recurrence rate. RESULTS: During the 5-year follow-up period, 29.2% of the patients (n = 31) had disease recurrence. Univariate analysis showed that predictors of recurrence included cavernous and sphenoid sinus invasions, optic chiasm compression, larger tumour volume, giant adenoma >4 cm, and gross total resection (GTR). Multivariate analysis showed that lactotroph tumour type, sphenoid sinus invasion, and GTR were independent predictors. Kaplan-Meier analysis revealed significant differences in the 5-year recurrence rate among the three independent predictors, with significantly lower recurrence rate in patients with lactotroph tumours and GTR, and a significantly higher recurrence risk in patients with sphenoid sinus invasion. CONCLUSIONS: Lactotroph tumour type, sphenoid sinus invasion, and GTR are independent predictors of postoperative PitNET recurrence. This study provides insights into the factors affecting postoperative PitNET recurrence.

PitNETs are the second most common intracranial tumour typePrognostic factors for postoperative PitNET recurrence remain not fully understoodWe explored potential prognostic factors in patients with postoperative PitNETsProlactin secretion and GTR failure were independent recurrence predictorsProliferative factors did not correlate with recurrence.

Common ground on immune infiltration landscape and diagnostic biomarkers in diabetes-complicated atherosclerosis: an integrated bioinformatics analysis.

Introduction: Type 2 diabetes mellitus (T2DM) is a major cause of atherosclerosis (AS). However, definitive evidence regarding the common molecular mechanisms underlying these two diseases are lacking. This study aimed to investigate the mechanisms underlying the association between T2DM and AS. Methods: The gene expression profiles of T2DM (GSE159984) and AS (GSE100927) were obtained from the Gene Expression Omnibus, after which overlapping differentially expressed gene identification, bioinformatics enrichment analyses, protein-protein interaction network construction, and core genes identification were performed. We confirmed the discriminatory capacity of core genes using receiver operating curve analysis. We further identified transcription factors using TRRUST database to build a transcription factor-mRNA regulatory network. Finally, the immune infiltration and the correlation between core genes and differential infiltrating immune cells were analyzed. Results: A total of 27 overlapping differentially expressed genes were identified under the two-stress conditions. Functional analyses revealed that immune responses and transcriptional regulation may be involved in the potential pathogenesis. After protein-protein interaction network deconstruction, external datasets, and qRT-PCR experimental validation, four core genes (IL1B, C1QA, CCR5, and MSR1) were identified. ROC analysis further showed the reliable value of these core genes. Four common differential infiltrating immune cells (B cells, CD4+ T cells, regulatory T cells, and M2 macrophages) between T2DM and AS datasets were selected based on immune cell infiltration. A significant correlation between core genes and common differential immune cells. Additionally, five transcription factors (RELA, NFκB1, JUN, YY1, and SPI1) regulating the transcription of core genes were mined using upstream gene regulator analysis. Discussion: In this study, common target genes and co-immune infiltration landscapes were identified between T2DM and AS. The relationship among five transcription factors, four core genes, and four immune cells profiles may be crucial to understanding T2DM complicated with AS pathogenesis and therapeutic direction.

Liquid Biopsy Instrument for Ultra-Fast and Label-Free Detection of Circulating Tumor Cells.

Rapid diagnosis and real-time monitoring are of great important in the fight against cancer. However, most available diagnostic technologies are time-consuming and labor-intensive and are commonly invasive. Here, we describe CytoExam, an automatic liquid biopsy instrument designed based on inertial microfluidics and impedance cytometry, which uses a deep learning algorithm for the analysis of circulating tumor cells (CTCs). In silico and in vitro experiments demonstrated that CytoExam could achieve label-free detection of CTCs in the peripheral blood of cancer patients within 15 min. The clinical applicability of CytoExam was also verified using peripheral blood samples from 10 healthy donors and >50 patients with breast, colorectal, or lung cancer. Significant differences in the number of collected cells and predicted CTCs were observed between the 2 groups, with variations in the dielectric properties of the collected cells from cancer patients also being observed. The ultra-fast and minimally invasive features of CytoExam may pave the way for new paths for cancer diagnosis and scientific research.

Morroniside attenuates podocytes lipid deposition in diabetic nephropathy: A network pharmacology, molecular docking and experimental validation study.

BACKGROUND: Dysregulation of lipid metabolism is a key factor influencing the progression of diabetic nephropathy (DN). Morroniside (MOR) is a major active compound isolated from the traditional Chinese herb Cornus officinalis, our previous research found that it can improve the lipid deposition of renal tubular epithelial cells. The purpose of this study is to explore whether MOR can improve podocyte lipid deposition and its mechanism of reducing DN. METHODS: Initially, we used network pharmacology and bioinformatics techniques to predict the relationship between renal lipid metabolism of MOR and DN. Subsequently, the binding activity of MOR with lipid-related proteins was studied by molecular docking to determine how MOR acts through these proteins. After determining the target of MOR, animal experiments and cell tests were carried out to verify it. RESULTS: Using network pharmacology, bioinformatics, and molecular docking, target proteins for MOR treatment of DN were predicted and screened, including PGC-1α, LXRs, ABCA1, PPARY, CD36, and nephrin. It is particularly noted that MOR effectively binds to PGC-1α, while LXRs, ABCA1, PPARY and CD36 are downstream molecules of PGC-1α. Silencing the PGC-1α gene significantly reduced the therapeutic effects of MOR. Conversely, in groups without PGC-1α knockdown, MOR was able to increase the expression levels of PGC-1α and influence the expression of downstream proteins. Furthermore, through in vivo and in vitro experiments, utilizing techniques such as lipid droplet staining, PAS, MASSON staining, immunofluorescence, and Western blot, we found that MOR effectively elevated the expression levels of the podocyte protein nephrin and lipid metabolism-regulating proteins PGC-1α, PPARY, and ABCA1, while significantly inhibiting the expression of the lipid accumulation promoter CD36. CONCLUSION: MOR can regulate the cholesterol efflux in podocytes via the PGC-1α/LXRs/ABCA1 signaling pathway, and control cholesterol intake via the PGC-1α/PPARY/CD36 signaling pathway, thereby ameliorating lipid deposition in DN.

Aptamer-functionalized triptolide with release controllability as a promising targeted therapy against triple-negative breast cancer.

Targeted delivery and precise release of toxins is a prospective strategy for the treatment of triple-negative breast cancer (TNBC), yet the flexibility to incorporate both properties simultaneously remains tremendously challenging in the X-drug conjugate fields. As critical components in conjugates, linkers could flourish in achieving optimal functionalities. Here, we pioneered a pH-hypersensitive tumor-targeting aptamer AS1411-triptolide conjugate (AS-TP) to achieve smart release of the toxin and targeted therapy against TNBC. The multifunctional acetal ester linker in the AS-TP site-specifically blocked triptolide toxicity, quantitatively sustained aptamer targeting, and ensured the circulating stability. Furthermore, the aptamer modification endowed triptolide with favorable water solubility and bioavailability and facilitated endocytosis of conjugated triptolide by TNBC cells in a nucleolin-dependent manner. The integrated superiorities of AS-TP promoted the preferential intra-tumor triptolide accumulation in xenografted TNBC mice and triggered the in-situ triptolide release in the weakly acidic tumor microenvironment, manifesting striking anti-TNBC efficacy and virtually eliminated toxic effects beyond clinical drugs. This study illustrated the therapeutic potential of AS-TP against TNBC and proposed a promising concept for the development of nucleic acid-based targeted anticancer drugs.

Charge Redistribution in High-Entropy Perovskite Oxide Porous Nanotubes Boosts Nitrate Electroreduction to Ammonia.

High-entropy perovskite oxides are promising materials in the field of electrocatalysis due to their advantages such as large spatial composition regulation, entropy effects, and tunable material properties. However, the preparation of high-entropy perovskite oxides with stable and controllable structures still remains challenging. Herein, we fabricated a series of high-entropy perovskite oxide porous nanotubes (PNTs) by electrospinning as efficient electrocatalysts for the nitrate reduction reaction (NO3RR). We further revealed that the different diffusion and decomposition behaviors of metal ions and polymers during the calcination process are the key to the formation of high-entropy perovskite oxide PNTs. Especially, LaSrNiCoMnFeCuO3 PNTs show excellent performance of the NO3RR, achieving the maximum NH3 Faradaic efficiency of almost 100%, yield rate of 1657.5 µg h-1 mgcat.-1, and durable stability after successive cycling, being one of the best electrocatalysts for the NO3RR. The mechanism studies show that the charge redistribution induced by the multisite synergistic effect and abundant unsaturated sites in the high-entropy perovskite oxide PNTs favors the adsorption of NO3- and key intermediates and reduces the catalytic energy barrier, thus further achieving high NO3- conversion efficiency.

Simultaneous biodegradation of polycyclic aromatic hydrocarbons and phthalates by bacterial consortium and its bioremediation for complex polluted soil and sewage sludge.

Simultaneous biodegradation of multiple micropollutantslike polycyclic aromatic hydrocarbons (PAHs) and phthalates (PAEs) by microbial consortia remain unclear. Here, four distinct bacterial consortia capable of degrading PAHs and PAEs were domesticated from sludge and its composts. PAH-degrading consortium HS and PAE-degrading consortium EC2 displayed the highest degradation efficiencies for PAHs (37 %-99 %) and PAEs (98 %-99 %), respectively, being significantly higher than those of individual member strains. Consortia HS and EC2 could simultaneously degrade both PAHs and PAEs. Remarkably, a synthetic consortium Syn by co-culturing consortia HS and EC2 demonstrated proficient simultaneous biodegradation for both PAHs (65 %-98 %) and PAEs (91 %-97 %). These consortia changed their community structure with enriching pollutant-degrading genera and extracellular polymeric substance contents to promote simultaneous biodegradation of multiple pollutants. Moreover, consortium Syn significantly enhanced degradation of both PAHs and PAEs in soil and sludge. This study provides strong candidates for simultaneous bioremediation of complex polluted environments by PAHs and PAEs.

A retrospective study on the impact of radiotherapy on the survival outcomes of small cell lung cancer patients based on the SEER database.

Small cell lung cancer (SCLC) patients exhibit significant heterogeneity in tumor burden, physical condition, and responses to initial treatment. This diversity in treatment responses can result in varying treatment outcomes. The primary objective of this study was to explore the patient demographics associated with improved survival outcomes through radiotherapy. Based on the SEER database, we identified 42,824 SCLC patients enrolled between 2004 and 2015. These patients were stratified into radiotherapy (n = 20,360) and non-radiotherapy groups (n = 22,464). We controlled for confounding factors using propensity score matching (PSM) analysis. Subsequently, Kaplan-Meier (KM) analysis was employed to evaluate the impact of radiotherapy on patients' overall survival (OS) and cancer-specific survival (CSS). Cancer-specific mortality was further analyzed using competitive risk models. Cox analysis was also conducted to examine additional variables potentially affecting the survival of SCLC patients. We identified a total of 42,824 eligible patients, and following PSM, 13,329 patients were successfully matched in both the radiotherapy and non-radiotherapy groups. The KM analysis showed that the median OS was 9 months in the radiotherapy group and 6 months in the non-radiotherapy group. The median CSS was 10 months in the radiotherapy group and 7 months in the non-radiotherapy group. The 5-year OS and 10-year OS rates were 6.2% versus 1.6% in the radiotherapy group and 2.6% versus 0.8% in the non-radiotherapy group (P < 0.001). Competitive risk analysis showed that cancer-specific mortality was significantly higher in the non-radiotherapy group than in the radiotherapy group (P < 0.001). Multivariate Cox analysis showed that the radiotherapy group (relative non-radiotherapy group) showed a significant positive effect on survival outcomes (OS: HR 0.658 95% CI [0.642, 0.675] P < 0.001; CSS: HR 0.662 95% CI [0.645, 0.679], P < 0.001). In addition, age, gender, race, primary tumor site, T stage, N stage, M stage, chemotherapy, and surgery were also considered as important predictors of SCLC outcome. The results of the subgroup analysis showed that the radiotherapy group showed a significant survival advantage regardless of age, sex, race, primary tumor site, M stage, chemotherapy, and surgery (P < 0.001). Radiotherapy may improve both OS and CSS in SCLC patients. Patients with SCLC may benefit from radiotherapy regardless of age, sex, race, primary tumor site, M stage, chemotherapy, and surgery.

IGF-1 inhibits inflammation and accelerates angiogenesis via Ras/PI3K/IKK/NF-κB signaling pathways to promote wound healing.

Exogenous insulin-like growth factor-1 (IGF-1) has been reported to promote wound healing through regulation of vascular endothelial cells (VECs). Despite the existing studies of IGF-1 on VEC and its role in angiogenesis, the mechanisms regarding anti-inflammatory and angiogenetic effects of IGF-1 remain unclear. In this study, we investigated the wound-healing process and the related signaling pathway of IGF-1 using an inflammation model induced by IFN-γ. The results demonstrated that IGF-1 can increase cell proliferation, suppress inflammation in VECs, and promote angiogenesis. In vivo studies further confirmed that IGF-1 can reduce inflammation, enhance vascular regeneration, and improve re-epithelialization and collagen deposition in acute wounds. Importantly, the Ras/PI3K/IKK/NF-κB signaling pathways was identified as the mechanisms through which IGF-1 exerts its anti-inflammatory and pro-angiogenic effects. These findings contribute to the understanding of IGF-1's role in wound healing and may have implications for the development of new wound treatment approaches.

Chronic Partial Sleep Deprivation Increased the Incidence of Atrial Fibrillation by Promoting Pulmonary Vein and Atrial Arrhythmogenesis in a Rodent Model.

Sleep deprivation (SD) is a recognized risk factor for atrial fibrillation (AF), yet the precise molecular and electrophysiological mechanisms behind SD-induced AF are unclear. This study explores the electrical and structural changes that contribute to AF in chronic partial SD. We induced chronic partial SD in Wistar rats using a modified multiple-platform method. Echocardiography demonstrated impaired systolic and diastolic function in the left ventricle (LV) of the SD rats. The SD rats exhibited an elevated heart rate and a higher low-frequency to high-frequency ratio in a heart-rate variability analysis. Rapid transesophageal atrial pacing led to a higher incidence of AF and longer mean AF durations in the SD rats. Conventional microelectrode recordings showed accelerated pulmonary vein (PV) spontaneous activity in SD rats, along with a heightened occurrence of delayed after-depolarizations in the PV and left atrium (LA) induced by tachypacing and isoproterenol. A Western blot analysis showed reduced expression of G protein-coupled receptor kinase 2 (GRK2) in the LA of the SD rats. Chronic partial SD impairs LV function, promotes AF genesis, and increases PV and LA arrhythmogenesis, potentially attributed to sympathetic overactivity and reduced GRK2 expression. Targeting GRK2 signaling may offer promising therapeutic avenues for managing chronic partial SD-induced AF. Future investigations are mandatory to investigate the dose-response relationship between SD and AF genesis.