Unveiling the hidden role of extracellular vesicles in brain metastases: a comprehensive review.

Background: Extracellular vesicles (EVs) are small, transparent vesicles that can be found in various biological fluids and are derived from the amplification of cell membranes. Recent studies have increasingly demonstrated that EVs play a crucial regulatory role in tumorigenesis and development, including the progression of metastatic tumors in distant organs. Brain metastases (BMs) are highly prevalent in patients with lung cancer, breast cancer, and melanoma, and patients often experience serious complications and are often associated with a poor prognosis. The immune microenvironment of brain metastases was different from that of the primary tumor. Nevertheless, the existing review on the role and therapeutic potential of EVs in immune microenvironment of BMs is relatively limited. Main body: This review provides a comprehensive analysis of the published research literature, summarizing the vital role of EVs in BMs. Studies have demonstrated that EVs participate in the regulation of the BMs immune microenvironment, exemplified by their ability to modify the permeability of the blood-brain barrier, change immune cell infiltration, and activate associated cells for promoting tumor cell survival and proliferation. Furthermore, EVs have the potential to serve as biomarkers for disease surveillance and prediction of BMs. Conclusion: Overall, EVs play a key role in the regulation of the immune microenvironment of brain metastasis and are expected to make advances in immunotherapy and disease diagnosis. Future studies will help reveal the specific mechanisms of EVs in brain metastases and use them as new therapeutic strategies.

Performance on adsorption of toluene by ionic liquid-modified AC in high-humidity exhaust gas.

Volatile organic compounds (VOCs) frequently pose a threat to the biosphere, impacting ecosystems, flora, fauna, and the surrounding environment. Industrial emissions of VOCs often include the presence of water vapor, which, in turn, diminishes the adsorption capacity and efficacy of adsorbents. This occurs due to the competitive adsorption of water vapor, which competes with target pollutants for adsorption sites on the adsorbent material. In this study, hydrophobic activated carbons (BMIMPF6-AC (L), BMIMPF6-AC (g), and BMIMPF6-AC-H) were successfully prepared using 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6) to adsorb toluene under humidity environment. The adsorption performance and mechanism of the resulting ionic liquid-modified activated carbon for toluene in a high-humidity environment were evaluated to explore the potential application of ionic liquids as hydrophobic modifiers. The results indicated that BMIMPF6-AC-H exhibited superior hydrophobicity. The toluene adsorption capacity of BMIMPF6-AC-H was 1.53 times higher than that of original activated carbon, while the adsorption capacity for water vapor was only 37.30% of it at 27 °C and 77% RH. The Y-N model well-fitted the dynamic adsorption experiments. To elucidate the microscopic mechanism of hydrophobic modification, the Independent Gradient Model (IGM) method was employed to characterize the intermolecular interactions between BMIMPF6 and toluene. Overall, this study introduces a new modifier for hydrophobic modification of activated carbon, which could enhance the efficiency of activated carbon in treating industrial VOCs.

Interplay between mesenchymal stem cells and macrophages: Promoting bone tissue repair.

The repair of bone tissue damage is a complex process that is well-orchestrated in time and space, a focus and difficulty in orthopedic treatment. In recent years, the success of mesenchymal stem cells (MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine. MSCs are closely related to macrophages. On one hand, MSCs regulate the immune regulatory function by influencing macrophages proliferation, infiltration, and phenotype polarization, while also affecting the osteoclasts differentiation of macrophages. On the other hand, macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment. The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration. Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair, and will also provide a reference for further application of MSCs in other diseases.

Association of Biological Age Acceleration with Cardiac Morphology, Function, and Incident Heart Failure: Insights from UK Biobank Participants.

BACKGROUND: Advanced age is associated with an increased risk of adverse cardiovascular events. The relationship between biological age acceleration (BAA), cardiac size, cardiac function, and heart failure (HF) is not well-defined. METHODS: Utilizing the UK Biobank cohort, we assessed biological age using the Klemera-Doubal and PhenoAge method. BAA was quantified by residual analysis compared to chronological age. Cardiovascular magnetic resonance (CMR) imaging provided detailed insights into cardiac structure and function. We employed multivariate regression to examine links between BAA and CMR-derived cardiac phenotypes. Cox proportional hazard regression models analyses was applied to explore the causative relationship between BAA and HF. Additionally, Mendelian randomization was used to investigate the genetic underpinnings of these associations. RESULTS: A significant correlation was found between increased BAA and deleterious changes in cardiac structure, such as diminished left ventricular mass, lower overall ventricular volume, and reduced stroke volumes across ventricles and atria. Throughout a median follow-up of 13.8 years, participants with greater biological aging showed a heightened risk of HF (26% per standard deviation [SD] increase in KDM-BA acceleration, 95% confidence intervals [CI]: 23%-28%; 33% per SD increase in PhenoAge acceleration, 95% CI: 32%-35%). Mendelian randomization analysis suggests a likely causal link between BAA, vital cardiac metrics, and HF risk. CONCLUSIONS: In this cohort, accelerated biological aging may serve as a risk indicator for altered cardiac dimensions, functionality, and the onset of heart failure among middle-aged and elderly adults. It holds promise as a focal point for evaluating risk and developing targeted interventions.

Carbothermal synthesis of sulfurized nano zero-valent iron from sulfate-reducing bacteria biomass for mercury removal: The first application of biomass sulfur source.

The development of low-cost, highly efficient adsorbent materials is of significant importance for environmental remediation. In this study, a novel material, sulfurized nano zero-valent iron loaded biomass carbon (S-nZVI/BC), was successfully synthesized by a simple manufacturing process. The preparation of S-nZVI/BC does not require the use of expensive and hazardous chemicals. Instead, residual sludge, a solid waste product, is used as feedstock. The sludge is rich in Sulfate-Reducing Bacteria (SRB), which can provide carbon and sulfur sources for the synthesis of S-nZVI/BC. It was observed that S-nZVI particles formed in situ were dispersed within BC and covered by it. Additionally, S-nZVI/BC inherited the large specific surface area and porosity of BC. The adsorption capacity of S-nZVI/BC can reach 857.55 mg g-1 Hg (II) during the remediation of mercury-polluted water. This research offers new perspectives for developing composites in terms of the low cost and harmlessness of raw materials.

Correlation between serum leptin level and sleep monitoring indexes in patients with obstructive sleep apnea hypopnea syndrome and its predictive value: a cross-sectional analysis.

Objective: To investigate the association between serum leptin (LP) level and polysomnography (PSG) parameters in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: A cross-sectional study was conducted. The data of subjects who underwent PSG at hospital between January 2021 and December 2022 were collected retrospectively, 220 participants were included. The subjects were categorized into simple snoring group (n = 45), mild OSAHS group (n = 63), moderate OSAHS group (n = 52), and severe OSAHS group (n = 60). The general characteristics, PSG indices, and serological indices were collected retrospectively. Pearson correlation analysis was used to observe the correlation between serum LP level and PSG parameters. The value of serum LP level in predicting OSAHS was analyzed by receiver operating characteristic curve. Results: The serum LP level was positively correlated with micro-arousal count, micro-arousal index (MAI), high apnea hypopnea index, times of blood oxygen decreased by≥3% and time in saturation lower 90%, and negatively correlated with lowest nocturnal oxygen saturation and mean oxygen saturation (p < 0.05). The area under the curve (AUC) of serum LP level in predicting the occurrence of OSAHS was 0.8276 (95% CI: 0.7713-0.8839), and when the Youden index was 0.587, the sensitivity was 72.00%, and the specificity was 86.67% (p < 0.0001). In the population with high MAI, the AUC of serum LP level in predicting the occurrence of OSAHS was 0.8825 (95% CI: 0.7833-0.9817), and when the Youden index was 0.690, the sensitivity was 79.00% and the specificity was 90.00% (p < 0.0001). Conclusion: Serum LP level is associated with the severity of OSAHS. Serum LP level demonstrates a strong predictive value for the occurrence of OSAHS, particularly in population with high MAI.

Export priority technique for Uni-portal thoracoscopic left upper lobectomy.

BACKGROUND: Further explore the safety and feasibility of Uni-portal video assisted thoracoscopic (UVATS) left upper lobectomy by optimizing the treatment of incisions and blood vessels. METHODS: We conducted a retrospective analysis of data from 32 patients who underwent UVATS left upper lobectomy and systematic mediastinal lymph node dissection utilizing the Export priority technique between January 2021 and December 2022. We documented perioperative indicators, including surgical time, intraoperative blood loss, the number of lymph nodes dissected, and postoperative pathological staging. RESULTS: All surgeries were conducted utilizing the Export priority technique in UVATS. The mean surgical duration was (98.93 ± 14.98) minutes, with an average intraoperative blood loss of (79.53 ± 37.96) ml. The mean count of dissected lymph nodes was (13.96 ± 2.69). The length of hospital Stay averaged (5.62 ± 1.81) days. On the first postoperative day, the thoracic drainage volume was (101.87 ± 49.46) ml. The mean duration of postoperative thoracic tube insertion was (3.1 ± 1.84) days. No occurrences of postoperative hoarseness, pulmonary infection, or complications such as bronchopleural fistula were observed. CONCLUSION: The application of the Export priority technique improves the safety and feasibility of UVATS left upper lobectomy.

SERPINB3/B4 is Increased in Psoriasis and Rosacea Lesions and has Pro-inflammatory Effects in Mouse Models of these Diseases.

Psoriasis and rosacea are both chronic inflammatory skin disorders resulted from aberrant keratinocyte-immune cell crosstalk, but the common molecular foundations for these two conditions are poorly understood. Here, we reveal that both psoriasis and rosacea patients, as well as their mice models, have significantly elevated expressions of SERPINB3/B4 (members of serine protease inhibitor) in the lesional skin. Skin inflammation in mice that resembles both psoriasis and rosacea is prevented by SERPINB3/B4 deficiency. Mechanistically, we demonstrate that SERPINB3/B4 positively induces NF-κB signaling activation, thereby stimulating disease-characteristic inflammatory chemokines and cytokines production in keratinocytes, and promoting the chemotaxis of CD4+ T cells. Our results suggest that, in keratinocytes, SERPINB3/B4 may be involved in the pathogenesis of both psoriasis and rosacea by stimulating NF-κB signaling, and they indicate a possible treatment overlap between these two diseases.

IL-15/IL-15Rα-Fc fusion protein XmAb24306 potentiates activity of CD3 bispecific antibodies through enhancing T cell expansion.

Insufficient quantity of functional T cells is a likely factor limiting clinical activity of T cell bispecific antibodies, especially in solid tumor indications. We hypothesized that XmAb24306 (efbalropendekin alfa), a lymphoproliferative interleukin (IL)-15/IL-15 receptor α (IL-15Rα) Fc-fusion protein, may potentiate the activity of T cell dependent (TDB) antibodies. Activation of human peripheral T cells by cevostamab, an anti-FcRH5/CD3 TDB, or anti-HER2/CD3 TDB resulted in upregulation of IL-2/15Rß (CD122) receptor subunit in nearly all CD8+ and majority of CD4+ T cells, suggesting that TDB treatment may sensitize T cells to the IL-15. XmAb24306 enhanced T cell bispecific antibody induced CD8+ and CD4+ T cell proliferation and expansion. In vitro combination of XmAb24306 with cevostamab or anti-HER2/CD3 TDB resulted in significant enhancement of tumor cell killing, which was reversed when T cell numbers were normalized, suggesting that T cell expansion is the main mechanism for the observed benefit. Pre-treatment of immune competent mice with a mouse-reactive surrogate of XmAb24306 (mIL-15-Fc) resulted in significant increase of T cells in blood, spleen and in tumors and converted transient anti-HER2/CD3 TDB responses to complete durable responses. In summary, our results support the hypothesis where the number of tumor infiltrating T cells is rate limiting for the activity of solid tumor targeting TDBs. Upregulation of CD122 by TDB treatment and the observed synergy with XmAb24306 and T cell bispecific antibodies supports clinical evaluation of this novel immunotherapy combination.

Rational Design of Nitride Phosphor-In-Glass with Robust Stability and Photoluminescence Performance.

Phosphor-in-glass represents a promising avenue for merging the luminous efficiency of high-quality phosphor and the thermal stability of a glass matrix. Undoubtedly, the glass matrix system and its preparation are pivotal factors in achieving high stability and preserving the original performance of embedded phosphor particles. In contrast to the well-established commercial Y3Al5O12:Ce3+ oxide phosphor, red nitride phosphor, which plays a critical role in high-quality lighting, exhibits greater structural instability during the high-temperature synthesis of inorganic glasses. A telluride glass with a refractive index (RI = 2.15@615 nm) akin to that of nitride phosphor (∼2.19) has been devised, demonstrating high efficiency in photon utilization. The lower glass-transition temperature plays a crucial role in safeguarding phosphor particles against erosion resulting from exposure to high-temperature melts. Phosphor-in-glass retains 93% of the quantum efficiency observed for pure phosphor. The assembled white light-emitting diodes module has precise color tuning capabilities, achieving an optimal color rendering index of 93.7, a luminous efficacy of 80.4 lm/W, and a correlated color temperature of 5850 K. These outcomes hold potential for advancing the realm of inorganic package and high-quality white light illumination.

Quercetin attenuates inflammation in rosacea by directly targeting p65 and ICAM-1.

AIMS: Rosacea is an inflammatory skin disease with immune and vascular dysfunction. Although there are multiple treatment strategies for rosacea, the clinical outcomes are unsatisfactory. MAIN METHODS: Combining transcriptome data and the Connectivity Map database quercetin was identified as a novel candidate for rosacea. Next, the therapeutic efficacy of quercetin was substantiated through proteomic analyses, in vivo experiments, and in vitro assays. Additionally, the utilization of DARTS, molecular docking and experimental verification revealed the therapeutic mechanisms of quercetin. KEY FINDINGS: Treatment with quercetin resulted in the following effects: (i) it effectively ameliorated rosacea-like features by reducing immune infiltration and angiogenesis; (ii) it suppressed the expression of inflammatory mediators in HaCaT cells and HDMECs; (iii) it interacted with p65 and ICAM-1 directly, and this interaction resulted in the repression of NF-κB signal and ICAM-1 expression in rosacea. SIGNIFICANCE: We show for the first time that quercetin interacted with p65 and ICAM-1 directly to alleviated inflammatory and vascular dysfunction, suggesting quercetin is a novel, promising therapeutic candidate for rosacea.

Clonal expansion of shared T cell receptors reveals the existence of immune commonality among different lesions of synchronous multiple primary lung cancer.

The increase in the detection rate of synchronous multiple primary lung cancer (MPLC) has posed remarkable clinical challenges due to the limited understanding of its pathogenesis and molecular features. Here, comprehensive comparisons of genomic and immunologic features between MPLC and solitary lung cancer nodule (SN), as well as different lesions of the same patient, were performed. Compared with SN, MPLC displayed a lower rate of EGFR mutation but higher rates of BRAF, MAP2K1, and MTOR mutation, which function exactly in the upstream and downstream of the same signaling pathway. Considerable heterogeneity in T cell receptor (TCR) repertoire exists among not only different patients but also among different lesions of the same patient. Invasive lesions of MPLC exhibited significantly higher TCR diversity and lower TCR expansion than those of SN. Intriguingly, different lesions of the same patient always shared a certain proportion of TCR clonotypes. Significant clonal expansion could be observed in shared TCR clonotypes, particularly in those existing in all lesions of the same patient. In conclusion, this study provided evidences of the distinctive mutational landscape, activation of oncogenic signaling pathways, and TCR repertoire in MPLC as compared with SN. The significant clonal expansion of shared TCR clonotypes demonstrated the existence of immune commonality among different lesions of the same patient and shed new light on the individually tailored precision therapy for MPLC.

Promoting agricultural waste-driven denitrification and nitrogen sequestration with nano-enabled strategy.

Nanotechnology and biotechnology offer promising avenues for bolstering food security through the facilitation of soil nitrogen (N) sequestration and the reduction of nitrate leaching. Nonetheless, a comprehensive and mechanistic evaluation of their effectiveness and safety remains unclear. In this study, a soil remediation strategy employing nano-Fe3O4 and straw in N-contaminated soil was developed to elucidate N retention mechanisms via diverse metagenomics techniques. The findings revealed that subsoil amended with straw, particularly in conjunction with nano-Fe3O4, significantly increased subsoil N content (53.2%) and decreased nitrate concentration (74.6%) in leachate. Furthermore, the enrichment of functional genes associated with N-cycling, sulfate, nitrate, and iron uptake, along with chemotaxis, and responses to environmental stimuli or microbial collaboration, effectively mitigates nitrate leaching while enhancing soil N sequestration. This study introduces a pioneering approach utilizing nanomaterials in soil remediation, thereby offering the potential for the cultivation of safe vegetables in high N input greenhouse agriculture.

In-Depth Insight into Corrosion Inhibition Performance of Sweet Potato Leaf Extract as a Green and Efficient Inhibitor for 6N01 Al Alloy in the Seawater: Experimental and Theoretical Perspectives.

Corrosion protection of metal has become an important and urgent topic, which requires the development of an inexpensive, environmentally friendly, and highly efficient corrosion inhibitor. Herein, a sweet potato leaf extract (SPL) was obtained by a simple water-based extraction method and then as a green corrosion inhibitor for 6N01 Al alloy in the seawater was well investigated by the weight loss method and various electrochemical tests. Fourier transform infrared (FT-IR) and ultraviolet-visible (UV-vis) spectroscopies were carried out to investigate the compositions of SPL. The findings from the potentiodynamic polarization (PDP) curves suggest that SPL functions as a typical mixed-type corrosion inhibitor. Notably, the maximum corrosion inhibition efficiency reaches 94.6% following a 36 h immersion period at 25 °C. The adsorption behavior of SPL on the Al alloy surface belongs to the Langmuir adsorption isotherm. The Gibbs free energy value illustrates that the adsorption of SPL contains both physisorption and chemisorption. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) indicate that SPL is firmly attached to the Al alloy surface by making a protective layer, which can effectively inhibit the corrosion of the Al alloy in the seawater. Furthermore, quantum chemical calculations were applied to validate the chemical adsorption and elucidate the relationship between the electronic structure of the active components in SPL and their effectiveness in corrosion inhibition.

Efficacy and Safety of Endoscopic Resection for Gastric Gastrointestinal Stromal Tumors Originating from the Muscularis Propria.

BACKGROUND: The role of endoscopic resection (ER) in gastric gastrointestinal stromal tumors (GISTs) has not been fully elucidated. AIMS: The purpose of this work was to evaluate the clinical effectiveness and safety of ER in patients with GISTs originating from the muscularis propria (MP). METHODS: A total of 233 consecutive patients with gastric GISTs originating from the MP layer, who underwent ER between February 2012 and May 2023, were included in this study. Clinical characteristics, tumor features, and outcomes were recorded and compared between patients who underwent en bloc resection and piecemeal resection. RESULTS: Among the 233 patients, the median size of GISTs was 12 mm (range 5-60 mm). Risk assessment categorized 190 patients as very low risk, 26 as low risk, 10 as moderate risk, and 7 as high risk. The procedures performed included endoscopic submucosal excavation (127 cases), endoscopic full-thickness resection (103 cases), and submucosal tunneling endoscopic resection (3 cases). The complete and R0 resection rate was 93.1%. Complications occurred in 4.7% of cases (perioperative perforations 1.7%, perioperative bleeding 1.3%, both 0.9%), resulting in conversion to surgery in 1.3% of cases. Risk factors associated with piecemeal resection were tumor size [odds ratio (OR) 0.402, 95% confidence interval (CI) 0.207-0.783; P = 0.007] and shape (OR 0.045, 95% CI 0.009-0.235; P < 0.001). CONCLUSIONS: ER is proven to be an effective and reasonably safe approach for gastric GISTs originating from the MP. Notably, larger tumor size and irregular shape are identified as risk factors for piecemeal resection during ER procedures.

Community responses of arbuscular mycorrhiza fungi to hydrological gradients in a riparian Phragmites australis wetland.

The hydrological regime is considered to be the major factor that affects the distribution of arbuscular mycorrhiza (AM) fungi in wetlands. We aimed to investigate the responses of AM fungal community to different hydrological gradients. Illumina Miseq sequencing technology was used to study the AM fungal community structure in roots and rhizosphere soils of Phragmites australis in different moisture areas (dry area, alternating wet and dry area, and flooded area) in Mengjin Yellow River wetland. The rhizosphere soils and roots hosted different AM fungal communities. In roots, the AM fungal colonization and Chao1 richness in dry area were significantly higher than that in alternating wet and dry area and flooded area, but the community composition did not vary clearly under different water conditions. In rhizosphere soils, the Chao1 richness of AM fungi in flooded area was significantly higher than that in alternating wet and dry area and dry area, and the AM fungal community structure obviously differed across different areas. The redundancy analyses indicated that changes in the AM fungal community in soils were associated with altered soil properties, and the abundance of the dominant genus Glomus was mostly positively correlated with alkali-hydrolyzable nitrogen in soils. This study helps us to understand the responses of AM fungal community to hydrological gradients in wetlands.

Effective synthesis of circRNA via a thermostable T7 RNA polymerase variant as the catalyst.

Introduction: Circular RNAs (circRNAs) are endogenous noncoding RNAs (ncRNAs) with transcriptional lengths ranging from hundreds to thousands. circRNAs have attracted attention owing to their stable structure and ability to treat complicated diseases. Our objective was to create a one-step reaction for circRNA synthesis using wild-type T7 RNA polymerase as the catalyst. However, T7 RNA polymerase is thermally unstable, and we streamlined circRNA synthesis via consensus and folding free energy calculations for hotspot selection. Because of the thermal instability, the permuted intron and exon (PIE) method for circRNA synthesis is conducted via tandem catalysis with a transcription reaction at a low temperature and linear RNA precursor cyclization at a high temperature. Methods: To streamline the process, a multisite mutant T7 RNA polymerase (S430P, N433T, S633P, F849I, F880Y, and G788A) with significantly improved thermostability was constructed, and G788A was used. Results: The resulting mutant exhibited stable activity at 45°C for over an hour, enabling the implementation of a one-pot transcription and cyclization reaction. The simplified circRNA production process demonstrated an efficiency comparable to that of the conventional two-step reaction, with a cyclization rate exceeding 95% and reduced production of immunostimulatory dsRNA byproducts.

Boosting the Faradaic Efficiency of Br--Mediated Photoelectrochemical Epoxidation by Local Acidity on α-Fe2O3.

The redox mediated photoelectrochemical (PEC) or electrochemical (EC) alkene oxidation process is a promising method to produce high value-added epoxides. However, due to the competitive reaction of water oxidation and overoxidation of the mediator, the utilization of the electricity is far below the ideal value, where the loss of epoxidation's faradaic efficiency (FE) is ≈50%. In this study, a Br-/HOBr-mediated method is developed to achieve a near-quantitative selectivity and ≈100% FE of styrene oxide on α-Fe2O3, in which low concentration of Br- as mediator and locally generated acidic micro-environment work together to produce the higher active HOBr species. A variety of styrene derivatives are investigated with satisfied epoxidation performance. Based on the analysis of local pH-dependent epoxidation FE and products distribution, the study further verified that HOBr serves as the true active mediator to generate the bromohydrin intermediate. It is believed that this strategy can greatly overcome the limitation of epoxidation FE to enable future industrial applications.