Exposure to air pollution and an unhealthy built environment increase disease risk by impacting metabolic risk factors and inflammation, potentially via epigenetic modifications and effects on gene expression. We aimed to explore associations between fine particulate matter (PM2.5), black carbon, ozone, nitrogen dioxide, distance to nearest water body, normalized difference vegetation index, and impervious surface and gene expression profiles in adults. This study is a part of the LongITools project and includes cross-sectional data from the Rotterdam Study, a population-based cohort study, and NoMa, a randomized controlled trial. Environmental exposures were assigned using land-use regression (LUR) models and satellite data. Gene expression was assessed with whole blood RNA sequencing (Rotterdam Study, n = 758) and microarray analyses in peripheral blood mononuclear cells (NoMa, n = 100). We analysed transcriptomic profiles and enriched pathways associated with each of the environmental exposures. PM2.5 had the strongest gene expression associations, while only a few significant associations were observed for the other environmental exposures. In both populations, exposure to PM2.5 was associated with genes and pathways related to inflammation, oxidative stress, DNA metabolism, cell cycle regulation, histones, electron transport chain, oxidative phosphorylation, and neural signalling. This study is limited by different methods for RNA quantification, a cross-sectional design, and a small sample size. However, in both populations, exposure to PM2.5 resulted in the maximum number of associations with gene expression. In conclusion, PM2.5 is strongly associated with various gene expression profiles, which provide information about the underlying mechanisms of the detrimental health effects of exposure to PM2.5.

Minerals, vitamins, and trace elements are examples of micronutrients essential for psychological wellbeing and brain function. Severe disorders may result from their deficiency or, conversely, from an excess of them. Recent studies have indicated that the etiopathogenesis of certain neurological disorders may involve chronically elevated micronutrient levels. Physiological functions, such as energy metabolism, neurotransmitter synthesis, and antioxidant defence, are regulated by these vital nutrients and are essential for optimal neuronal activity. According to new research, micronutrient enrichment, whether through diet or supplements, can have a significant impact on cognitive function, neuroplasticity, and brain development. Cognitive decline, memory loss, and attention problems are linked to deficiencies in essential micronutrients, including vitamin B12, iron, zinc, and omega-3 fatty acids. Tailored micronutrient therapies have shown promise in reducing age-related cognitive decline and enhancing mental function in both healthy individuals and those at greater risk. This manuscript emphasizes the growing research linking micronutrient status to cognitive health. It also highlights the importance of maintaining a balanced diet and following appropriate supplementation practices to optimize brain function throughout life.

Periodontal ligament (PDL) consists mainly of collagen fiber bundles with specialized mechanoreceptors and free nerve endings that connect the cementum of the tooth root to alveolar bone and are vital for dental proprioceptive function. When a tooth is lost and replaced with a dental implant, osseointegration occurs without the intervening PDL, leading to a loss of proprioceptive function. Herein we report the placement, and healthy integration of an advanced dental implant in the socket of rat study models without facilitating the process of osseointegration, that could possibly impart proprioceptive features comparable to those noted in natural teeth. The experimental surgical procedure during dental implant installation in rat models involved various oral tissue structures surrounding the teeth as analogous to those in human subjects and therefore bears a significant clinical relevance. Additionally, the surgical procedure detailed here confers the advantages of its use to investigate not only dental implants but also could be explorative for a wide range of extra-oral implants for improved neural integration.

Bone regeneration continues to be a major clinical challenge, requiring the creation of multifunctional biomaterials that integrate osteogenic and antibacterial properties to reduce the risk of post-surgical infections. This study investigates the fabrication and characterization of composite coatings comprising zinc oxide nanoparticles (ZnO-NPs) incorporated into a SiO2-CaO-P2O5-B2O3-Na2O bioactive glass matrix with ethylcellulose as a binder on AISI 316 L stainless steel substrates. The coatings were deposited via electrophoretic deposition in isopropanol suspension at 80 V for 5 min, with ZnO-NP concentrations of 1 g/L (Z1) and 2 g/L (Z2). Comprehensive analyses of microstructure, phase composition, and surface roughness were conducted for the coatings. Physicochemical characterization confirmed the successful integration of ZnO-NPs within the bioactive glass (BG) matrix. Corrosion resistance studies in phosphate-buffered saline over 14 days demonstrated superior performance of the Z1 coating. Surface roughness measurements revealed a texture conducive to cell growth (similar to 2.1 mu m). Cytocompatibility assessments using human placental mesenchymal stem cells showed enhanced cellular viability, attachment, and proliferation on the coated samples. Antibacterial efficacy against Escherichia coli and Staphylococcus aureus was evaluated, with the ZnO-loaded coatings exhibiting acceptable inhibitory effects. The combination of improved corrosion resistance, favorable surface properties, adequate cytocompatibility, and enhanced antibacterial activity suggests that these composite coatings hold promise for advanced bone regeneration applications. This study provides insights into the development of multifunctional coatings that address the dual challenges of promoting osteogenesis and preventing bacterial infection in orthopedic implants.

The pseudo-binary phases in the In2Se3-Ga2Se3 system have drawn attention due to their interesting structural features and exciting non-linear optical (NLO) properties. Although the phases have been known since 1977, detailed structural characterization has not been carried out in previous studies. In this research program, the pseudo-binary In2-xGaxSe3 (x = 0.6-1.4) (hexagonal, P65/P61) has been prepared using high-temperature synthesis and characterized using X-ray diffraction techniques and DFT calculations. For x ≤ 1, the structure is similar to the parent γ-In2Se3 and adopts the layered defect wurtzite type (γ1), where gallium preferentially substitutes the tetrahedrally coordinated indium site without affecting the indium in the trigonal bipyramidal (TBP) environment. At x = 1, the ordered γ1-GaInSe3 is formed. In the compositional range 1.2 < x ≤ 1.4, an ideal defect wurtzite structure (γ2) is observed, where both cationic sites are tetrahedrally coordinated by selenium. Ga occupies one of the two tetrahedrally coordinated cationic sites in this region, while the other site is statistically occupied by Ga and In. Interestingly, at x = 1.2, the structure is heavily disordered and can be interpreted as an incoherent intergrowth of γ1- and γ2-phases. A detailed theoretical calculation is performed on various compounds in the III2-VI3 family (e.g., α-Al2S3, α-Ga2S3, γ-In2Se3, and InGaSe3) to reveal the preference of Ga for tetrahedral co-ordination in the pseudo-binary In2-xGaxSe3.

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer, and despite low incidence rates, it remains the sixth leading cause of cancer related deaths worldwide. Immunotherapy, which aims to enhance the immune system’s ability to recognize and eliminate cancer cells, has emerged as a promising approach in the battle against PDAC. PARP7, a mono-ADP-ribosyltransferase, is a negative regulator of the type I interferon (IFN-I) pathway and has been reported to reduce anti-tumour immunity.MethodsWe used murine pancreatic cancer cells, CR705, CRISPR/Cas9, in vivo tumour models and spectral flow cytometry to determine the role of PARP7 in pancreatic tumour growth.ResultsLoss of Parp7 elevated the levels of interferon stimulated gene factor 3 (ISGF3) and its downstream target genes, even in the absence of STING. Cancer cells knocked out for Parp7 (CR705Parp7KO) produced smaller tumours than control cells (CR705Cas9) when injected into immunocompetent mice. Transcriptomic analyses revealed that CR705Parp7KO tumours had increased expression of genes involved in immunoregulatory interactions and interferon signalling pathways. Characterization of tumour infiltrating leukocyte (TIL) populations showed that CR705Parp7KO tumours had higher proportions of natural killer cells, CD8+ T cells and a lower proportion of anti-inflammatory macrophages (M2). The overall TIL profile of CR705Parp7KO tumours was suggestive of a less suppressive microenvironment.ConclusionsOur data show that loss of Parp7 reduces PDAC tumour growth by increasing the infiltration of immune cells and enhancing anti-tumour immunity. These findings provide support to pursue PARP7 as a therapeutic target for cancer treatment.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease which remains poorly understood. Increasing evidence suggests that the aryl hydrocarbon receptor (AHR) plays a role in the pathogenesis of several cancers; however, its role in PDAC is unclear because AHR exhibits both pro- and anti-tumor activities. Here we evaluated the role of AHR in CR705 and K8484 murine PDAC cells in vitro and CR705 cells in vivo. Loss of Ahr did not affect cell proliferation compared with Cas9 control cells and no differences in tumor development between CR705Cas9 and CR705AhrKO cells were observed in immunocompromised mice. Conversely, tumors from CR705AhrKO cells grew more slowly than tumors from CR705Cas9 cells in immune competent mice. RNA sequencing identified 1279 genes upregulated and 586 genes downregulated in CR705AhrKO tumors compared with CR705Cas9 tumors. Pathway analysis identified immunoregulatory interactions, interferon signaling, and chemokine signaling among the top upregulated pathways. Increased infiltration of CD45+ cells and higher numbers of CD8+ T cells and F4/80+ cells were observed in CR705AhrKO tumors. Ahr deficiency in macrophages (LysMCre) or lymphocytes (RorcCre) did not alter tumor development of CR705Cas9 cells compared with Ahrfl/fl mice. CR705AhrKO tumors in RorcCre mice, but not in LysMCre mice had significantly lower tumor weights normalized to body weights compared with CR705AhrKO tumors in WT mice. These findings show that Ahr loss in CR705 pancreatic cancer cells is sufficient to induce proinflammatory gene responses that contribute to increased immune cell infiltration and reduced tumor growth.

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In contemporary power electronics, Insulated Gate Bipolar Transistors (IGBTs) are extremely important for various reasons.IGBTs serve as vital components in microgrid inverters, providing the switching capabilities required to transform DC electricity from renewable sources into high-quality AC power for microgrid (MG) applications.A bidirectional inverter (BDI) is an essential component of a microgrid, allowing for the smooth integration of distributed energy resources (DERs) and supporting both gridconnected and islanded operations.In a bidirectional DC/AC inverter (BDAI), IGBTs play an important role in managing the flow of electricity in both directions.The consequences of bidirectional inverter's IGBT failures on a microgrid might vary from small power quality concerns to more serious interruptions in stability and system performance.Therefore, IGBT should operate without failure.This paper illustrates a method for identifying an early IGBT switch failure (ISF) in a bidirectional microgrid inverter that is linked to a photovoltaic (PV) and battery energy storage system (BESS).An analysis of the inverter output current signal using the Fast Fourier Transform (FFT) has been undertaken to discover faults.Afterwards, the impacts on the DC, fundamental current component, and harmonic distortions have been investigated for various levels of fault.A successful detection of the ISF has been attempted, based on the best-fit features.An ISF detection algorithm also has been proposed.

Adiponectin is an antidiabetic endogenous adipokine that plays a protective role against the unfavorable metabolic sequelae of obesity. Recent evidence suggests a sinister link between hypoadiponectinemia and development of insulin resistance/type 2 diabetes (T2D). Adiponectin's insulin-sensitizing property is mediated through the specific adiponectin receptors R1 and R2, which activate the AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor (PPAR) α pathways. AdipoAI is a novel synthetic analogue of endogenous adiponectin with possibly similar pharmacological effects. Thus, there is a need of orally active small molecules that activate Adipoq subunits, and their downstream signaling, which could ameliorate obesity related type 2 diabetes. In the study we aim to investigate the effects of AdipoAI on obesity and T2D. Through in-vitro and in-vivo analyses, we investigated the antidiabetic potentials of AdipoAI and compared it with AdipoRON, another orally active adiponectin receptors agonist. Our results showed that in-vitro treatment of AdipoAI (0-5 µM) increased adiponectin receptor subunits AdipoR1/R2 with increase in AMPK and APPL1 protein expression in C2C12 myotubes. Similarly, in-vivo, oral administration of AdipoAI (25 mg/kg) observed similar effects as that of AdipoRON (50 mg/kg) with improved control of blood glucose and insulin sensitivity in diet-induced obesity (DIO) mice models. Further, AdipoAI significantly reduced epididymal fat content with decrease in inflammatory markers and increase in PPAR-α and AMPK levels and exhibited hepatoprotective effects in liver. Further, AdipoAI and AdipoRON also observed similar results in adipose tissue. Thus, our results suggest that low doses of orally active small molecule agonist of adiponectin AdipoAI can be a promising therapeutic target for obesity and T2D.

We must address active matter in the context of soft boundaries in order to bridge the gap between our understanding of active matter and the dynamics of the biological systems (that the active matter represent) under natural conditions. However, the physics of such active drops (matter) in contact with a soft and deformable surface has remained elusive. In this letter, we attempt to fill this gap and develop a theory for soft, active wetting. Our theory, which accounts for the various free energies for passive substrate and active drops as well as the active stresses, provides an equilibrium description of (active) particle orientation inside the drop and an equilibrium shape of the drop-soft-solid system. We obtain the equation relating the activity to the internal pressure of an active drop. The equilibrium calculation yields an ordered state of the polarization field inside the drop. The presence of the extensile (contractile) activity is found to make the drop press into the soft surface (come out of the soft surface), while increasing (decreasing) the wetting radius as compared to non-active drops. Finally, the three-phase contact line undergoes a rotation that depends on the strength of activity. These findings shed new light on the manner in which the active stresses interact with surface tension and elasticity at the fundamental level.

The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor which in certain cancer types drives pro-survival processes that facilitate tumorigenesis, malignant cell migration, invasion, and metastasis. Much of AHR’s pro-tumorigenic action is due to its activation by the oncometabolite, kynurenine. Because of this AHR antagonists are being actively investigated as new anti-tumor therapy. In this study we compared the effects of treatment with the AHR antagonists, BAY2416964 and GNF351, to that of AHR knockout in PyMT murine mammary cancer cells. BAY2416964 and GNF351 effectively inhibited kynurenine-dependent increases in Cyp1a1 and Cyp1b1 mRNA levels. CRISPR/Cas9-generated PyMT AhrKO cells exhibited reduced cell proliferation compared with controls, but treatment with 1 μM BAY2416964 for 96 h had no effect on the proliferation of wildtype cells. To further examine the differences between AHR knockout and short term BAY2416964, we generated long-term BAY2416964 (LT-BAY) cells by exposing wildtype cells to 1 μM BAY2416964 for at least 6 weeks. Similar to AhrKO cells, LT-BAY cells exhibited reduced cell proliferation and migration compared with wildtype cells. No differentially expressed genes (DEGs) were identified in wildtype cells exposed to 1 μM BAY2416964 for 24 h; however, 46.4% of DEGs overlapped between AhrKO and LT-BAY cells including gene regulated cell proliferation. Our data reveal long-term pharmacological inhibition of AHR by BAY2416964 closely resembles AHR loss in a mouse model of breast cancer.

[This corrects the article DOI: 10.3389/fonc.2024.1466658.].

Environmental exposures, including air pollutants and lack of natural spaces, are associated with suboptimal health outcomes in children. We aimed to study the associations between environmental exposures and gene expression in children. Associations of exposure to particulate matter (PM) with diameter <2.5 (PM2.5) and < 10 (PM10) micrometers, nitrogen dioxide, green spaces, and blue space, with whole-blood gene expression were explored in children from the Dutch Generation R Study (n = 172). Analyses were adjusted for age, sex, batch, maternal education, and area socioeconomic status. Follow-up analysis was carried out using lymphoblastoid cell line gene expression in children from the ALSPAC Study (n = 946). Gene set enrichment analysis (GSEA) using hallmark and immune gene sets from the molecular signature database was carried out to identify significantly over-represented gene sets for insights into biological mechanisms Exposure to PM2.5 was associated with expression of 86 genes in discovery analyses in the Generation R Study [false discovery rate (FDR)-adjusted P-value < .25]. Of these, PM2.5 was also associated with GNG11 expression in the same direction in follow-up analysis (FDR-adjusted P-value < .05). The remaining exposures showed much fewer associations in the discovery analyses. GSEA using PM2.5 association results for both cohorts indicated suppression of gene sets related to interferon response and response to bacterial and viral exposure. In conclusion, gene expression analysis performed in two independent cohorts suggests that PM2.5 exposure in children may be involved in interferon and microbial infection responses.

Scaffolds play a crucial role in bone tissue engineering to support the defect area through bone regeneration and defect reconstruction. Promising tissue regeneration without negative repercussions and avoidance of the lifelong presence inside the body make bioresorbable metals prosper in the field of regenerative medicine. Recently, Zn and its alloys have emerged as promising biodegradable materials for their moderate degradation rate and satisfactory biocompatibility. Nevertheless, it is very challenging for cells to adhere and grow over the Zn surface alone, which influences the tissue-implant integration. In this study, an attempt has been made to systematically investigate the bioactivity responses in terms of in vitro hemocompatibility, cytotoxicity, antibacterial activity, and in vivo biocompatibility of newly developed Zn-2Cu-0.5Mn/Mg alloy scaffolds with different surface roughness. The rough surface of Zn-2Cu-0.5Mg shows the highest degradation rate of 0.16 mm/yr. The rough surface exhibits a prominent role in the adsorption of protein, further enhancing cell adhesion. Concentration-dependent alloy extract shows the highest cell proliferation for 12.5% of the extract with a maximum cell viability of 101% in Zn-2Cu-0.5Mn and 108% in Zn-2Cu-0.5Mg after 3 d. Acceptable hemolysis percentages (less than 5%) with promising anticoagulation properties are observed for all of the conditions. Enhanced antibacterial (Staphylococcus aureus and Escherichia coli) activity due to a significant effect of ions illustrates the maximum killing effect on the bacterial colony for the rough Zn-2Cu-0.5Mg alloy. In addition, it is observed that for rough Zn-2Cu-0.5Mn/Mg alloys, the inflammatory response is minimal after subcutaneous implantation, and neo-bone tissue forms in the defect areas of the rat femur with satisfactory biosafety response. The osseointegration property of the Zn-2Cu-0.5Mg alloy is comparable to that of the Zn-2Cu-0.5Mn alloy. Therefore, the rough surface of the Zn-2Cu-0.5Mg alloy has the potential to enhance biocompatibility and promote better osseointegration activity with host tissues for various biomedical applications.

To understand the reliability and repairablityof electronics printed using the AJP process, through experimental and computational modeling, to take full advantage of this technology and realize its industrial potential. This work is sponsored by the members of the CALCE at the University of Maryland, College Park and Laboratory for Physical Science.

OBJECTIVES:The objective was to report and compare the complications and recurrence rates of urethral prolapse in dogs when treated with urethropexy, resection and anastomosis or a combined surgical technique.STUDY DESIGN:Retrospective study.MATERIALS AND METHODS:A total of 86 dogs were identified from the medical records of 10 veterinary referral hospitals from February 2012 and October 2022. Dogs were included if they underwent surgery for a urethral prolapse at first presentation. Complications were classified as minor or major based on the necessity of further surgical intervention. Complications leading to death were also considered major complications.RESULTS:Seventy-nine dogs were included, urethropexy (n=44), resection and anastomosis (n=27) and a combined surgical technique (n=8). Minor complications were identified in 41 of 79 dogs (51.9%): urethropexy 19 of 44 (43.2%), resection and anastomosis 18 of 27 (66.6%) and a combined surgical technique four of eight (50%). Major complications occurred in 23 dogs (29.1%), of which 21 were recurrence (26.6%). Recurrence occurred in 17 of 44 dogs following a urethropexy (38.6%), three of 27 dogs following resection and anastomosis (11.1%) and one of eight dogs treated with a combined surgical technique (12.5%). Recurrence of a urethral prolapse was significantly more likely following urethropexy in comparison to resection and anastomosis.CLINICAL SIGNIFICANCE:Resection and anastomosis was associated with a lower recurrence rate in comparison to urethropexy for the surgical treatment of urethral prolapse. Based on these results, we concluded that resection and anastomosis may be preferable to urethropexy for treatment of urethral prolapse at first presentation. Urethropexy, and resection and anastomosis combined surgical technique was associated with low recurrence rate; however, further studies will be needed to clarify if it provides any benefit over resection and anastomosis.