Diesel Particulate Matter Permeation into Normal Human Skin and Intervention Using a Topical Ceramide Formulation.

INTRODUCTION: Diesel particulate matter (DPM) emitted from diesel engines is a major source of air pollutants. DPM is composed of elemental carbon, which adsorbs organic compounds including toxic polycyclic aromatic hydrocarbons (PAHs). The skin, as well as airways, is directly exposed to DPM, and association of atopic dermatitis, psoriasis flares, and premature skin aging with air pollutant levels has been documented. In skin, the permeation of DPM and DPM-adsorbed compounds is primarily blocked by the epidermal permeability barrier deployed in the stratum corneum. Depending upon the integrity of this barrier, certain amounts of DPM and DPM-adsorbed compounds can permeate into the skin. However, this permeation into human skin has not been completely elucidated. METHODS: We assessed the permeation of PAHs (adsorbed to DPM) into skin using ex vivo normal (barrier-competent) organ-cultured human skin after application of DPM. Two major PAHs, 2-methylnaphthalene and triphenylene, and a carcinogenic PAH, benzo(a)pyrene, all found in DPM, were measured in the epidermis and dermis using liquid chromatography electrospray ionization tandem mass spectrometry. In addition, we investigated whether a topical formulation can attenuate the permeation of DPM into skin. RESULTS: 2-Methylnaphthalene, triphenylene, and benzo(a)pyrene were recovered from the epidermis. Although these PAHs were also detected in the dermis after DPM application, these PAH levels were significantly lower than those found in the epidermis. We also demonstrated that a topical formulation that has the ability to form more uniform membrane structures can significantly suppress the permeation of PAHs adsorbed to DPM into the skin. CONCLUSION: Toxic compounds adsorbed by DPM can permeate even barrier-competent skin. Hence, barrier-compromised skin, such as in atopic dermatitis, psoriasis, and xerosis, is even more vulnerable to air pollutants. A properly formulated topical mixture that forms certain membrane structures on the skin surface can effectively prevent permeation of exogenous substances, including DPM, into skin.

Nanowatt-Level Photoactivated Gas Sensor Based on Fully-Integrated Visible MicroLED and Plasmonic Nanomaterials.

Photoactivated gas sensors that are fully integrated with micro light-emitting diodes (µLED) have shown great potential to substitute conventional micro/nano-electromechanical (M/NEMS) gas sensors owing to their low power consumption, high mechanical stability, and mass-producibility. Previous photoactivated gas sensors mostly have utilized ultra-violet (UV) light (250-400 nm) for activating high-bandgap metal oxides, although energy conversion efficiencies of gallium nitride (GaN) LEDs are maximized in the blue range (430-470 nm). This study presents a more advanced monolithic photoactivated gas sensor based on a nanowatt-level, ultra-low-power blue (λpeak  = 435 nm) µLED platform (µLP). To promote the blue light absorbance of the sensing material, plasmonic silver (Ag) nanoparticles (NPs) are uniformly coated on porous indium oxide (In2 O3 ) thin films. By the plasmonic effect, Ag NPs absorb the blue light and spontaneously transfer excited hot electrons to the surface of In2 O3 . Consequently, high external quantum efficiency (EQE, ≈17.3%) and sensor response (ΔR/R0 (%) = 1319%) to 1 ppm NO2 gas can be achieved with a small power consumption of 63 nW. Therefore, it is highly expected to realize various practical applications of mobile gas sensors such as personal environmental monitoring devices, smart factories, farms, and home appliances.

The Epidermal Environment's Influence on the Dermal Environment in Response to External Stress.

INTRODUCTION: The outermost layer of the skin, the epidermis, is directly exposed to external stress (e.g., irradiation, allergens, and chemicals). Changes in epidermal conditions/environment in response to this stress could also influence conditions of the dermis, located directly beneath the epidermis. Yet, whether/how any epidermal environment changes in response to external stress affect dermal functions has not been completely clarified. METHODS: We employed ultraviolet irradiation B (UVB) (which hardly reaches the dermis) as a model of external stress. Human keratinocytes and human dermal fibroblasts were treated with UVB and conditioned medium of keratinocytes exposed to UVB (UVB-keratinocyte-M), respectively. We assessed (1) inflammatory cytokines and lipid mediators in keratinocytes; (2) matrix metalloprotease (MMP) levels and collagen degradation in fibroblasts; (3) ex vivo organ-cultured human skin was treated with UVB. MMP levels and collagen degradation were examined; (4) test whether the mixture of agent (agent cocktail) consisting of dihydroceramide, niacin amide, resveratrol, glucosyl hesperidin, and phytosterol ester that has been shown to improve skin barrier integrity can mitigate influence of UVB in skin; and (5) a pilot one-arm human clinical test to assess efficacy of formulation containing agent cocktail on stratum corneum hydration, skin elasticity, and wrinkle index. RESULTS: Inflammatory-cytokine and -lipid mediator production were increased in cultured keratinocytes treated with UVB, while matrix MMP-1, -3, and -9 production and collagen degradation were increased in fibroblasts incubated with UVB-keratinocyte-M. mRNA expression of COL1A1 (that codes type 1 collagen) levels was decreased in fibroblasts incubated with UVB-keratinocyte-M. The study using ex vivo organ-cultured human skin showed both MMP-1 and MMP-9 expression were increased in both epidermis and dermis and increased dermal collagen degradation following UVB irradiation. Increased MMP production and collagen degradation were attenuated by application of an agent cocktail. Finally, a pilot clinical study demonstrated that the formulation containing our agent cocktail likely has the ability to improve skin hydration, increase skin elasticity, and reduce the appearance of wrinkles. CONCLUSION: Epidermal changes in epidermal environment and conditions in response to external stress affect dermal conditions, and these negative effects of external stress on various skin layers can be pharmacologically mitigated.

Precisely Localized Bone Regeneration Mediated by Marine-Derived Microdroplets with Superior BMP-2 Binding Affinity.

Prompt and robust bone regeneration has been clinically achieved using supraphysiological doses of bone morphogenetic protein-2 (BMP-2) to overcome the short half-life and rapid clearance. However, uncontrolled burst release of exogenous BMP-2 causes severe complications such as heterotopic ossification and soft tissue inflammation. Therefore, numerous researches have focused on developing a new BMP-2 delivery system for a sustained release profile by immobilizing BMP-2 in various polymeric vehicles. Herein, to avoid denaturation of BMP-2 and enhance therapeutic action via localized delivery, a complex coacervate consisting of fucoidan, a marine-derived glycosaminoglycan, and poly-l-lysine (PLL) is fabricated. Superior BMP-2 binding ability and electrostatic interaction-driven engulfment enable facile and highly efficient microencapsulation of BMP-2. The microencapsulation ability of the coacervate significantly improves BMP-2 bioactivity and provides protection against antagonist and proteolysis, while allowing prolonged release. Moreover, BMP-2 containing coacervate is coated on conventional collagen sponges. The bioactivity and localized bone regenerating ability are confirmed through in vitro (human-derived stem cells), and in vivo (calvarial bone defect model) evaluations.

Integration of Bioinspired Fibrous Strands with 3D Spheroids for Environmental Hazard Monitoring.

Numerous methods have been introduced to produce 3D cell cultures that can reduce the need for animal experimentation. This study presents a unique 3D culture platform that features bioinspired strands of electrospun nanofibers (BSeNs) and aquatic cell lines to compensate for shortcomings in the current cell spheroid generation techniques. The use of BSeNs in 3D zebrafish liver cell cultures is found to improve liver and reproductive functions through spheroid-based in vitro assays such as whole transcriptome sequencing and reproductive toxicity testing, with optimized properties exhibiting results similar to those obtained for fish embryo acute toxicity (FET, OECD TG 236) following exposure to environmental endocrine-disrupting chemicals (17ß-Estradiol (E2), 4-hydroxytamoxifen (4-HT), and bisphenol compounds (bisphenol A (BPA) and 9,9-Bis(4-hydroxyphenyl)fluorene (BPFL)). These findings indicate that the beneficial effects of bioinspired materials that closely mimic ECM environments can yield efficient zebrafish cells with intrinsic functions and xenobiotic metabolism similar to those of zebrafish embryos. As a closer analog for the in vivo conditions that are associated with exposure to potentially hazardous chemicals, the straightforward culture model introduced in this study shows promise as an alternative tool that can be used to further eco-environmental assessment.

Development of Organic/Inorganic Hybrid Materials for Fully Degradable Reactive Oxygen Species-Releasing Stents for Antirestenosis.

Despite innovative advances in stent technology, restenosis remains a crucial issue for the clinical implantation of stents. Reactive oxygen species (ROS) are known to potentially accelerate re-endothelialization and lower the risk of restenosis by selectively controlling endothelial cells and smooth muscle cells. Recently, several studies have been conducted to develop biodegradable polymeric stents. As biodegradable polymers are not electrically conductive, double metallic layers are required to constitute a galvanic couple for ROS generation. Here, we report a new biodegradable hybrid material composed of a biodegradable polymer substrate and double anodic/cathodic metallic layers for enhancing re-endothelialization and suppressing restenosis. Pure Zn and Mg films (3 µm thick) were deposited onto poly-l-lactic acid (PLLA) substrates by DC magnetron sputtering, and a long-term immersion test using biodegradable hybrid materials was performed in phosphate-buffered solution (PBS) for 2 weeks. The concentrations of superoxide anions and hydrogen peroxide generated by the corrosion of biodegradable metallic films were monitored every 1 or 2 days. Both superoxide anions and hydrogen peroxide were seamlessly generated even after the complete consumption of the anodic Mg layer. It was confirmed that the superoxide anions and hydrogen peroxide were formed not only by the galvanic corrosion between the anode and cathode layers but also by the corrosion of a single Mg or Zn layer. The corrosion products of the Mg and Zn films in PBS were phosphate, oxide, or chloride of the biodegradable metals. Thus, it is concluded that ROS generation by the corrosion of PLLA-based hybrid materials can be sustained until the exhaustion of the cathode metal layer.

Mechanical characteristics of metal nanoparticle thin film on flexible substrate exposed to saline solution.

The robust and reliable mechanical characteristics of metal nanoparticle (NP) thin films on flexible substrates are important because they operate under tensile, bending, and twisting loads. Furthermore, in wearable printed electronics applications, salty solutions such as sweat and seawater can affect the mechanical reliabilities of devices. In this paper, we investigated the effect of sodium chloride (NaCl) solutions on silver (Ag) NP thin films on flexible polymer substrate. After exposure to NaCl solution of Ag NP thin film, we observed the aggregation behavior between Ag NPs and formation of larger pores in the film due to the removal of organic capping layer from the surface of Ag NPs. The average porosity and 5% deviation strains of Ag NP thin films on the polyimide substrate were dramatically increased and decreased from 2.99% to 9.64% and from 3.94% to 0.87%, respectively, after exposure to NaCl solution for 1 h. Also, we verified a drastic deterioration of the surface adhesion of the Ag NP thin film to the substrate by exposure to NaCl solution. We could observe crack propagation and delamination by in-situ scanning electron microscope imaging. In addition, passivation effect by a parylene layer for preventing the permeation of the saline solution was investigated.

Discovery of Orphan Olfactory Receptor 6M1 as a New Anticancer Target in MCF-7 Cells by a Combination of Surface Plasmon Resonance-Based and Cell-Based Systems.

Olfactory receptors (ORs) account for 49% of all G protein-coupled receptors (GPCRs), which are important targets for drug discovery, and hence ORs may also be potential drug targets. Various ORs are expressed in breast cancer cells; however, most of them are orphan receptors, and thus, their functions are unknown. Herein, we present an experimental strategy using a surface plasmon resonance (SPR) system and a cell-based assay that allowed the identification of orphan OR6M1 as a new anticancer target in the MCF-7 breast cancer cell line. After the construction of stable OR6M1-expressing cells, the SPR-based screening of 108 chemicals for ligand activity was performed against OR6M1-expressing whole cells (primary screening) or membrane fragments (secondary screening). As a result, anthraquinone (AQ) and rutin were discovered to be new OR6M1 ligands. Based on calcium imaging in OR6M1-expressing Hana3A cells, AQ and rutin were classified as an OR6M1 agonist and antagonist, respectively. Cell viability and live/dead assays showed that AQ induced the death of MCF-7 cells, which was inhibited by rutin. Therefore, OR6M1 may be considered an anticancer target, and AQ may be considered a chemotherapeutic agent. This combined method can be widely used to discover the ligands and functions of other orphan GPCRs.

MicroRNAs and Calcium Signaling in Heart Disease.

In hearts, calcium (Ca2+) signaling is a crucial regulatory mechanism of muscle contraction and electrical signals that determine heart rhythm and control cell growth. Ca2+ signals must be tightly controlled for a healthy heart, and the impairment of Ca2+ handling proteins is a key hallmark of heart disease. The discovery of microRNA (miRNAs) as a new class of gene regulators has greatly expanded our understanding of the controlling module of cardiac Ca2+ cycling. Furthermore, many studies have explored the involvement of miRNAs in heart diseases. In this review, we aim to summarize cardiac Ca2+ signaling and Ca2+-related miRNAs in pathological conditions, including cardiac hypertrophy, heart failure, myocardial infarction, and atrial fibrillation. We also discuss the therapeutic potential of Ca2+-related miRNAs as a new target for the treatment of heart diseases.

Expression of human olfactory receptor 10J5 in heart aorta, coronary artery, and endothelial cells and its functional role in angiogenesis.

ORs are ectopically expressed in non-chemosensory tissues including muscle, kidney, and keratinocytes; however, their physiological roles are largely unknown. We found that human olfactory receptor 10J5 (OR10J5) is expressed in the human aorta, coronary artery, and umbilical vein endothelial cells (HUVEC). Lyral induces Ca(2+) and phosphorylation of AKT in HUVEC. A knockdown study showed the inhibition of the lyral-induced Ca(2+) and the phosphorylation AKT and implied that these processes are mediated by OR10J5. In addition, lyral enhanced migration of HUVEC, which were also inhibited by RNAi in a migration assay. In addition, matrigel plug assay showed that lyral enhanced angiogenesis in vivo. Together these data demonstrate the physiological role of OR10J5 in angiogenesis and represent roles of ORs in HUVEC cells.

Limonin, a Component of Dictamni Radicis Cortex, Inhibits Eugenol-Induced Calcium and cAMP Levels and PKA/CREB Signaling Pathway in Non-Neuronal 3T3-L1 Cells.

Limonin, one of the major components in dictamni radicis cortex (DRC), has been shown to play various biological roles in cancer, inflammation, and obesity in many different cell types and tissues. Recently, the odorant-induced signal transduction pathway (OST) has gained attention not only because of its function in the perception of smell but also because of its numerous physiological functions in non-neuronal cells. However, little is known about the effects of limonin and DRC on the OST pathway in non-neuronal cells. We investigated odorant-stimulated increases in Ca(2+) and cAMP, major second messengers in the OST pathway, in non-neuronal 3T3-L1 cells pretreated with limonin and ethanol extracts of DRC. Limonin and the extracts significantly decreased eugenol-induced Ca(2+) and cAMP levels and upregulated phosphorylation of CREB and PKA. Our results demonstrated that limonin and DRC extract inhibit the OST pathway in non-neuronal cells by modulating Ca(2+) and cAMP levels and phosphorylation of CREB.

A Review of Recent Advancements in Sensor-Integrated Medical Tools.

A medical tool is a general instrument intended for use in the prevention, diagnosis, and treatment of diseases in humans or other animals. Nowadays, sensors are widely employed in medical tools to analyze or quantify disease-related parameters for the diagnosis and monitoring of patients' diseases. Recent explosive advancements in sensor technologies have extended the integration and application of sensors in medical tools by providing more versatile in vivo sensing capabilities. These unique sensing capabilities, especially for medical tools for surgery or medical treatment, are getting more attention owing to the rapid growth of minimally invasive surgery. In this review, recent advancements in sensor-integrated medical tools are presented, and their necessity, use, and examples are comprehensively introduced. Specifically, medical tools often utilized for medical surgery or treatment, for example, medical needles, catheters, robotic surgery, sutures, endoscopes, and tubes, are covered, and in-depth discussions about the working mechanism used for each sensor-integrated medical tool are provided.

Risk of Dementia and Alzheimer's Disease Associated With Antidiabetics: A Bayesian Network Meta-Analysis.

INTRODUCTION: Dementia risk is substantially elevated in patients with diabetes. However, evidence on dementia risk associated with various antidiabetic regimens is still limited. This study aims to comprehensively investigate the risk of dementia and Alzheimer's disease (AD) associated with various antidiabetic classes. METHODS: Cochrane Central Register of Controlled Trials, Embase, MEDLINE (PubMed), and Scopus were searched from inception to March 2024 (PROSPERO CRD 42022365927). Observational studies investigating dementia and AD incidences after antidiabetic initiation were identified. Bayesian network meta-analysis was performed to determine dementia and AD risks associated with antidiabetics. Preferred Reporting Items for Systematic Reviews-Network Meta-Analyses (PRISMA-NMA) guidelines were followed. Statistical analysis was performed and updated in November 2023 and March 2024, respectively. RESULTS: A total of 1,565,245 patients from 16 studies were included. Dementia and AD risks were significantly lower with metformin and sodium glucose co-transporter-2 inhibitors (SGLT2i). Metformin displayed the lowest risk of dementia across diverse antidiabetics, whereas α-glucosidase inhibitors demonstrated the highest risk. SGLT2i exhibited the lowest dementia risk across second-line antidiabetics. Dementia risk was significantly higher with dipeptidyl peptidase-4 inhibitor (DPP4i), metformin, sulfonylureas, and thiazolidinediones (TZD) compared to SGLT2i in the elderly (≥75 years). Dementia risk associated with metformin was substantially lower, regardless of diabetic complication status or baseline A1C. DISCUSSION: Metformin and SGLT2i demonstrated lower dementia risk than other antidiabetic classes. Patient-specific factors may affect this relationship and cautious interpretation is warranted as metformin is typically initiated at an earlier stage with fewer complications. Hence, further large-scaled clinical trials are required.

Schisandrin A in Schisandra chinensis Upregulates the LDL Receptor by Inhibiting PCSK9 Protein Stabilization in Steatotic Model.

Schisandra chinensis extract (SCE) protects against hypocholesterolemia by inhibiting proprotein convertase subtilisin/kexin 9 (PCSK9) protein stabilization. We hypothesized that the hypocholesterolemic activity of SCE can be attributable to upregulation of the PCSK9 inhibition-associated low-density lipoprotein receptor (LDLR). Male mice were fed a low-fat diet or a Western diet (WD) containing SCE at 1% for 12 weeks. WD increased final body weight and blood LDL cholesterol levels as well as alanine transaminase and aspartate aminotransferase expression. However, SCE supplementation significantly attenuated the increase in blood markers caused by WD. SCE also attenuated WD-mediated increases in hepatic LDLR protein expression in the obese mice. In addition, SCE increased LDLR protein expression and attenuated cellular PCSK9 levels in HepG2 cells supplemented with delipidated serum (DLPS). Non-toxic concentrations of schisandrin A (SA), one of the active components of SCE, significantly increased LDLR expression and tended to decrease PCSK9 protein levels in DLPS-treated HepG2 cells. High levels of SA-mediated PCSK9 attenuation was not attributable to reduced PCSK9 gene expression, but was associated with free PCSK9 protein degradation in this cell model. Our findings show that PCSK9 secretion can be significantly reduced by SA treatment, contributing to reductions in free cholesterol levels.

Mechanical Activation of Graphite for Na-Ion Battery Anodes: Unexpected Reversible Reaction on Solid Electrolyte Interphase via X-Ray Analysis.

Although sodium-ion batteries (SIBs) offer promising low-cost alternatives to lithium-ion batteries (LIBs), several challenges need to be overcome for their widespread adoption. A primary concern is the optimization of carbon anodes. Graphite, vital to the commercial viability of LIBs, has a limited capacity for sodium ions. Numerous alternatives to graphite are explored, particularly focusing on disordered carbons, including hard carbon. However, compared with graphite, most of these materials underperform in LIBs. Furthermore, the reaction mechanism between carbon and sodium ions remains ambiguous owing to the structural diversity of disordered carbon. A straightforward mechanical approach is introduced to enhance the sodium ion storage capacity of graphite, supported by comprehensive analytical techniques. Mechanically activated graphite delivers a notable reversible capacity of 290.5 mAh·g-1 at a current density of 10 mA·g-1. Moreover, it maintains a capacity of 157.7 mAh·g-1 even at a current density of 1 A·g-1, benefiting from the defect-rich structure achieved by mechanical activation. Soft X-ray analysis revealed that this defect-rich carbon employs a sodium-ion storage mechanism distinct from that of hard carbon. This leads to an unexpected reversible reaction on the solid electrolyte surface. These insights pave the way for innovative design approaches for carbon electrodes in SIB anodes.

Barrier Abnormalities in Type 1 Diabetes Mellitus: The Roles of Inflammation and Ceramide Metabolism.

Xerosis is a common sign of both type 1 and type 2 diabetes mellitus (DM), and patients with DM and mouse models for DM show a compromised epidermal permeability barrier. Barrier defects then allow the entry of foreign substances into the skin, triggering inflammation, infection, and worsening skin symptoms. Characterizing how barrier abnormalities develop in DM could suggest treatments for xerosis and other skin disease traits. Because the proper ratio, as well as proper bulk amounts, of heterogeneous ceramide species are keys to forming a competent barrier, we investigated how ceramide metabolism is affected in type 1 DM using a mouse model (induced by streptozotocin). Chronic inflammation, evident in the skin of mice with DM, leads to (i) decreased de novo ceramide production through serine racemase activation-mediated attenuation of serine palmitoyl transferase activity by D-serine; (ii) changes in ceramide synthase activities and expression that modify the ratio of ceramide molecular species; and (iii) increased ceramide-1-phosphate, a proinflammatory lipid mediator, that stimulates inflammatory cytokine expression (TNFα and IFN-γ). Together, chronic inflammation affects ceramide metabolism, which attenuates epidermal permeability barrier formation, and ceramide-1-phosphate could amplify this inflammation. Alleviation of chronic inflammation is a credible approach for normalizing barrier function and ameliorating diverse skin abnormalities in DM.

Approaching pancreatic duct through pancreaticojejunostomy site with double ballon enteroscope in patients with Roux-en-Y anatomy.

BACKGROUND/AIMS: Double balloon enteroscopy (DBE)-assisted endoscopic retrograde cholangiopancreatography (ERCP) is frequently performed in patients with surgically altered intestinal anatomy. Moreover, it is also utilized in some cases with pancreatic indications, particularly patients with Roux-en-Y anatomy following Whipple's procedure or pylorus-preserving pancreaticoduodenectomy. Here, we present our experiences using DBE-assisted ERCP in patients with Roux-en-Y anatomy, with a focus on pancreatic indications. METHODOLOGY: Peroral DBE was attempted in 10 patients with Roux-en-Y anatomy. Conventional ERCP had previously been unsuccessful in all 10 patients. We retrospectively analyzed the relevant data of these patients. RESULTS: Four patients were male (40%) and the median age of the patients was 68 years. A complete evaluation of the afferent loops was possible in eight cases (80%) and selective cannulation was successful in six cases (60%). Therapeutic interventions were tried in four patients, and were successful in all of them. We tried to approach pancreatic duct through pancreaticojejunal anastomosis and performed therapeutic intervention successfully such as removal of pancreaticoliths or dilation of stricture of pancreaticojejunostomy site in two of three patients. CONCLUSIONS: DBE-assisted ERCP appears to be a useful tool for the diagnosis and treatment of pancreatobiliary lesions in patients with a Roux-en-Y reconstruction, especially those with pancreatic indications.

Epigenetic Profiling of Type 2 Diabetes Mellitus: An Epigenome-Wide Association Study of DNA Methylation in the Korean Genome and Epidemiology Study.

Diabetes is characterized by persistently high blood glucose levels and severe complications and affects millions of people worldwide. In this study, we explored the epigenetic landscape of diabetes using data from the Korean Genome and Epidemiology Study (KoGES), specifically the Ansung-Ansan (AS-AS) cohort. Using epigenome-wide association studies, we investigated DNA methylation patterns in patients with type 2 diabetes mellitus (T2DM) and those with normal glucose regulation. Differential methylation analysis revealed 106 differentially methylated probes (DMPs), with the 10 top DMPs prominently associated with TXNIP, PDK4, NBPF20, ARRDC4, UFM1, PFKFB2, C7orf50, and ABCG1, indicating significant changes in methylation. Correlation analysis highlighted the association between the leading DMPs (e.g., cg19693031 and cg26974062 for TXNIP and cg26823705 for NBPF20) and key glycemic markers (fasting plasma glucose and hemoglobin A1c), confirming their relevance in T2DM. Moreover, we identified 62 significantly differentially methylated regions (DMRs) spanning 61 genes. A DMR associated with PDE1C showed hypermethylation, whereas DMRs associated with DIP2C, FLJ90757, PRSS50, and TDRD9 showed hypomethylation. PDE1C and TDRD9 showed a strong positive correlation between the CpG sites included in each DMR, which have previously been implicated in T2DM-related processes. This study contributes to the understanding of epigenetic modifications in T2DM. These valuable insights can be utilized in identifying potential biomarkers and therapeutic targets for effective management and prevention of diabetes.

Low-Power, Multi-Transduction Nanosensor Array for Accurate Sensing of Flammable and Toxic Gases.

Toxic and flammable gases pose a major safety risk in industrial settings; thus, their portable sensing is desired, which requires sensors with fast response, low-power consumption, and accurate detection. Herein, a low-power, multi-transduction array is presented for the accurate sensing of flammable and toxic gases. Specifically, four different sensors are integrated on a micro-electro-mechanical-systems platform consisting of bridge-type microheaters. To produce distinct fingerprints for enhanced selectivity, the four sensors operate based on two different transduction mechanisms: chemiresistive and calorimetric sensing. Local, in situ synthesis routes are used to integrate nanostructured materials (ZnO, CuO, and Pt Black) for the sensors on the microheaters. The transient responses of the four sensors are fed to a convolutional neural network for real-time classification and regression of five different gases (H2 , NO2 , C2 H6 O, CO, and NH3 ). An overall classification accuracy of 97.95%, an average regression error of 14%, and a power consumption of 7 mW per device are obtained. The combination of a versatile low-power platform, local integration of nanomaterials, different transduction mechanisms, and a real-time machine learning strategy presented herein helps advance the constant need to simultaneously achieve fast, low-power, and selective gas sensing of flammable and toxic gases.

Patulin Ameliorates Hypertrophied Lipid Accumulation and Lipopolysaccharide-Induced Inflammatory Response by Modulating Mitochondrial Respiration.

Patulin (PAT) is a natural mycotoxin found in decaying pome fruits. Although some toxicological studies have been conducted on PAT, recent research has highlighted its anticancer and antifungal effects. However, studies have yet to examine the effects and molecular mechanisms of PAT in other metabolic diseases. Obesity is a chronic disease caused by excessive food intake and abnormal lifestyle, leading to low-grade inflammation. Therefore, this study aimed to elucidate the effect of PAT on obesity at the cellular level. PAT treatment reduced lipid accumulation, suppressed glucose and LDL uptake, inhibited lipid deposition and triglyceride synthesis, upregulated fatty acid oxidation-related genes (Pgc1α), and downregulated adipogenic/lipogenic genes (Pparγ and C/ebpα) in hypertrophied 3T3-L1 adipocytes. Additionally, PAT treatment enhanced mitochondrial respiration and mass in differentiated adipocytes and alleviated inflammatory response in activated RAW 264.7 macrophages. Moreover, PAT treatment downregulated pro-inflammatory genes (il-6, Tnf-α, Cox-2, and inos), suppressed lipopolysaccharide (LPS)-induced increase in inflammatory mediators (IL-6, TNF-α, and NO), and restored mitochondrial oxidative function in LPS-stimulated macrophages by improving oxygen consumption and mitochondrial integrity and suppressing ROS generation. Overall, these findings suggest a potential for PAT in the prevention of lipid accumulation and inflammation-related disorders.