Image J as the quantification tool in endosonography strain elastography may be reflected in the disturbance of endocrine pancreatic dysfunction.

Objectives: Pancreatic fibrosis is one of the main pathological features of chronic pancreatitis (CP), suggesting a strong relationship between CP and pancreatic ductal cancer. There was no available data about pancreatic fibrosis and pancreatic dysfunction in the early CP (ECP) using endosonography (EUS). Methods: Asymptomatic patients with pancreatic enzyme abnormalities (AP-P; n = 56) and patients with ECP (n = 21) were determined by the absence of abnormal findings on upper gastrointestinal endoscopy, abdominal ultrasonography, and abdominal computed tomography. An Olympus EUS (GF-UCT 260; Olympus) was used to perform EUS. Open software "Image J", developed by NIH, was used to measure the surface area fraction of the designated elastic blue region. The maximum value among the pancreatic head, pancreatic body, and pancreatic tail was defined as the ELST-blue score. The exocrine and endocrine pancreatic functions were evaluated using the N-benzoyl-l-tyrosyl-p-aminobenzoic acid (BT-PABA) test and homeostasis model assessment of ß-cell function (HOMA-ß) value, respectively. Results: EUS score, lobularity, and hyperechoic foci/strands in patients with ECP were significantly (p < 0.001) higher than those in patients with AP-P. In addition, there were no significant differences in the BT-PABA test (73.1 ± 25.5, 68.5 ± 15.6) and HOMA-ß (93.1 ± 67.4, 73.5 ± 139.7) between patients with ECP and AP-P. The ELST-blue score measured by image J as the quantification tool in EUS strain elastography in patients with ECP was significantly higher (p = 0.002) than that in patients with AP-P. Interestingly, the ELST-blue score was significantly associated with HOMA-ß in patients with ECP. Conclusions: The ELST-blue score may be a useful tool for the evaluation of endocrine pancreatic dysfunction in the ECP.

The structure-function relationships and techno-functions of ß-conglycinin.

ß-conglycinin (ß-CG) is a prominent storage protein belonging to the globulin family in soybean (Glycine max) seeds. Along with other soybean proteins, it serves as an important source of essential amino acids and high-quality nutrition. However, the digestibility and nutritional value of ß-CG are key factors affecting the nutritional profile of soy-based foods. The heterotrimeric, secondary, and quaternary structures of ß-CG, particularly the spatial arrangement of its α, α', and ß subunits, influence its functional properties. Considering these aspects, ß-CG emerges as a significant protein with diverse applications in the food and health sectors. Therefore, this review explores ß-CG's composition, structure, function, health implications, and industrial uses. Salient discussions are presented on its molecular structure, nutrition, digestibility, allergenicity, and techno-functions including emulsification, solubility, gelling, and structure-function complexities. Overall, the multifaceted potential of ß-CG in the healthcare sector and the food industry is evident.

Comparison between Spectral-Domain and Swept-Source OCT Angiography for the Measurement of Persistent Hypertransmission Defects in Age-Related Macular Degeneration.

Purpose: Spectral-domain OCT angiography (SD-OCTA) scans were tested in an algorithm developed for use with swept-source OCT angiography (SS-OCTA) scans to determine if SD-OCTA scans yielded similar results for the detection and measurement of persistent choroidal hypertransmission defects (hyperTDs). Design: Retrospective study. Participants: Forty pairs of scans from 32 patients with late-stage nonexudative age-related macular degeneration (AMD). Methods: Patients underwent both SD-OCTA and SS-OCTA imaging at the same visit using the 6 × 6 mm OCTA scan patterns. Using a semiautomatic algorithm that helped with outlining the hyperTDs, 2 graders independently validated persistent hyperTDs, which are defined as having a greatest linear dimension ≥250 µm on the en face images generated using a slab extending from 64 to 400 µm beneath Bruch's membrane. The number of lesions and square root (sqrt) total area of the hyperTDs were obtained from the algorithm using each imaging method. Main Outcome Measures: The mean sqrt area measurements and the number of hyperTDs were compared. Results: The number of lesions and sqrt total area of the hyperTDs were highly concordant between the 2 instruments (rc = 0.969 and rc = 0.999, respectively). The mean number of hyperTDs was 4.3 ± 3.1 for SD-OCTA scans and 4.5 ± 3.3 for SS-OCTA scans (P = 0.06). The mean sqrt total area measurements were 1.16 ± 0.64 mm for the SD-OCTA scans and 1.17 ± 0.65 mm for the SS-OCTA scans (P < 0.001). Because of the small standard error of the differences, the mean difference between the scans was statistically significant but not clinically significant. Conclusions: Spectral-domain OCTA scans provide similar results to SS-OCTA scans when used to obtain the number and area measurements of persistent hyperTDs through a semiautomated algorithm previously developed for SS-OCTA. This facilitates the detection of atrophy with a more widely available scan pattern and the longitudinal study of early to late-stage AMD. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Quantification of Total Ketone Bodies in Biological Matrices Using Stable Isotope-Labeled Internal Standards and RP-UHPLC-MS/MS.

Acetoacetate (AcAc) and D-beta-hydroxybutyrate (D-ßOHB), the two major ketone bodies found in circulation, are linked to multiple physiological and pathophysiological states. Therefore, analytical methodologies surrounding the quantification of total ketone body (TKB) concentrations in biological matrices are paramount. Traditional methods to quantify TKBs relied on indirect spectrophotometric assays with narrow dynamic ranges, which have been significantly improved upon by modern mass spectrometry (MS)-based approaches. However, the lack of stable isotope-labeled internal standards (ISs) for AcAc and the need to distinguish D-ßOHB from its closely related structural and enantiomeric isomers pose significant obstacles. Here, we provide a protocol to synthesize and quantify a [13C] stable isotope-labeled IS for AcAc, which, in conjunction with a commercially available [2H] stable isotope-labeled IS for ßOHB, allows TKBs to be measured across multiple biological matrices. This rapid (7 min) analysis employs reverse phase ultra-high performance liquid chromatography (RP-UHPLC) coupled to tandem MS (MS/MS) to distinguish ßOHB from three structural isomers using parallel reaction monitoring (PRM), providing excellent specificity and selectivity. Finally, a method is provided that distinguishes D-ßOHB from L-ßOHB using a simple one-step derivatization to produce the corresponding diastereomers, which can be chromatographically resolved using the same rapid RP-UHPLC separation with new PRM transitions. In summary, this method provides a rigorous analytical pipeline for the analysis of TKBs in biological matrices via leveraging two authentic stable isotope-labeled ISs and RP-UHPLC-MS/MS.

Improved production of class I phosphatidylinositol 4,5-bisphosphate 3-kinase.

Phosphatidylinositol 4,5-bisphosphate 3-kinases (PI3K) are a family of kinases whose activity affects pathways needed for basic cell functions. As a result, PI3K is one of the most mutated genes in all human cancers and serves as an ideal therapeutic target for cancer treatment. Expanding on work done by other groups we improved protein yield to produce stable and pure protein using a variety of modifications including improved solubility tag, novel expression modalities, and optimized purification protocol and buffer. By these means, we achieved a 40-fold increase in yield for p110α/p85α and a 3-fold increase in p110α. We also used these protocols to produce comparable constructs of the ß and δ isoforms of PI3K. Increased yield enhanced the efficiency of our downstream high throughput drug discovery efforts on the PIK3 family of kinases.

Diosmetin-7-O-ß-D-glucopyranoside from Pogostemonis Herba alleviated SARS-CoV-2-induced pneumonia by reshaping macrophage polarization and limiting viral replication.

ETHNOPHARMACOLOGICAL RELEVANCE: Viral pneumonia is the leading cause of death after SARS-CoV-2 infection. Despite effective at early stage, long-term treatment with glucocorticoids can lead to a variety of adverse effects and limited benefits. The Chinese traditional herb Pogostemonis Herba is the aerial part of Pogostemon Cablin (Blanco) Benth., which has potent antiviral, antibacterial, anti-inflammatory, and anticancer effects. It was used widely for treating various throat and respiratory diseases, including COVID-19, viral infection, cough, allergic asthma, acute lung injury and lung cancer. AIM OF THE STUDY: To investigate the antiviral and anti-inflammatory effects of chemical compounds from Pogostemonis Herba in SARS-CoV-2-infected hACE2-overexpressing mouse macrophage RAW264.7 cells and hACE2 transgenic mice. MATERIALS AND METHODS: The hACE2-overexpressing RAW264.7 cells were exposed with SARS-CoV-2. The cell viability was detected by CCK8 assay and cell apoptotic rate was by flow cytometric assay. The expressions of macrophage M1 phenotype markers (TNF-α and IL-6) and M2 markers (IL-10 and Arg-1) as well as the viral loads were detected by qPCR. The mice were inoculated intranasally with SARS-CoV-2 omicron variant to induce viral pneumonia. The levels of macrophages, neutrophils, and T cells in the lung tissues of infected mice were analyzed by full spectrum flow cytometry. The expressions of key proteins were detected by Western blot assay. RESULTS: Diosmetin-7-O-ß-D-glucopyranoside (DG) presented the strongest anti-SARS-CoV-2 activity. Intervention with DG at the concentrations of 0.625-2.5 µM not only reduced the viral replication, cell apoptosis, and the productions of inflammatory cytokines (IL-6 and TNF-α) in SARS-CoV-2-infected RAW264.7 cells, but also reversed macrophage polarity from M1 to M2 phenotype. Furthermore, treatment with DG (25-100 mg/kg) alleviated acute lung injury, and reduced macrophage infiltration in SARS-COV-2-infected mice. Mechanistically, DG inhibited SARS-COV-2 gene expression and HK3 translation via targeting YTHDF1, resulting in the inactivation of glycolysis-mediated NF-κB pathway. CONCLUSIONS: DG exerted the potent antiviral and anti-inflammatory activities. It reduced pneumonia in SARS-COV-2-infected mice via inhibiting the viral replication and accelerating M2 macrophage polarization via targeting YTHDF1, indicating its potential for COVID-19 treatment.

Development of a reusable polymeric fluorescence sensor based on acryloyl ß-cyclodextrin for the determination of aflatoxin B1 in grain products.

AFB1 is a harmful substance that can be found in agricultural products and can seriously affect human health, even in trace amounts. Therefore, monitoring AFB1 levels to ensure food safety and protect public health is crucial. New, highly reliable, selective, and rapid detection methods are needed to achieve this goal. Our work involves the development of a polymeric membrane sensor using radical polymerization that can accurately detect AFB1. Various spectroscopic techniques (Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM)) were used to obtain information about the structural and morphological properties of the prepared sensor. The sensor displayed fluorescence selectively responsive to AFB1 at the excitation wavelength of 376 nm and emission wavelength of 423 nm. The polymeric fluorescence sensor showed good sensitivity and a wide linear range from 9.61 × 10-10 and 9.61 × 10-9 mol/L for AFB1quantification. The limit of detection (LOD) is as low as 3.84 × 10-10 mol/L for AFB1. Other mycotoxins, such as aflatoxin B2 and aflatoxin G1, did not interfere with the sensor's high selectivity towards AFB1. To test the sensor's effectiveness in detecting AFB1 in real samples, three different grain samples - peanuts, hazelnut butter, and peanuts with a sauce known to contain AFB1 - were utilized. The results were satisfactory and demonstrated that the sensor can be successfully employed in real samples, with an error range of 0.43 % to 12.10 %.

In Vitro and In Vivo Evaluation of Virus-Induced Innate Immunity in Mouse.

The innate immune system is the first line of host defense against infection by pathogenic microorganisms, among which macrophages are important innate immune cells. Macrophages are widely distributed throughout the body and recognize and eliminate viruses through pattern recognition receptors (PRRs) to sense pathogen-associated molecular patterns (PAMPs). In the present chapter, we provide detailed protocols for vesicular stomatitis virus (VSV) amplification, VSV titer detection, isolation of mouse primary peritoneal macrophages, in vitro and in vivo VSV infection, detection of interferon-beta (IFN-ß) expression, and lung injury. These protocols provide efficient and typical methods to evaluate virus-induced innate immunity in vitro and in vivo.

Effects of isoprene on the ozonolysis of Δ3-carene and ß-caryophyllene: Mechanisms of secondary organic aerosol formation and cross-dimerization.

Elucidating the mutual effects between the different volatile organic compounds (VOCs) is crucial for comprehending the formation mechanism of atmospheric secondary organic aerosols (SOA). Here, the mixed VOCs experiments of isoprene and Δ3-carene/ß-caryophyllene were carried out in the presence of O3 using an indoor smog chamber. The suppression effect of isoprene was recognized by the scanning mobility particle sizer spectrometer, online vacuum ultraviolet free electron laser (VUV-FEL) photoionization aerosol mass spectrometry, and quantum chemical calculations. The results indicate that the suppression effect of isoprene on the ozonolysis of Δ3-carene and ß-caryophyllene shows fluctuating and monotonous trends, respectively. The carbon content of the precursor could be the main factor for regulating the strength of the suppression effect. Plausible structures and formation mechanisms of several new products generated from the single VOC precursor and VOC-cross-reaction are proposed, which enrich the category of VOC oxidation products. Meanwhile, a new dimerization mechanism of the RO2 + R'O2 reaction is suggested, which offers an intriguing perspective on the gas phase formation process of particle phase accretion products. The present findings provide valuable insights into clarifying the pivotal roles played by isoprene in the interplay between different VOCs and understanding of SOA formation mechanisms of VOC mixtures, especially nearby the emission origins.

SULF1 expression is increased and promotes fibrosis through the TGF-ß1/SMAD pathway in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive interstitial lung disease of unknown etiology. Despite the increasing global incidence and poor prognosis, the exact pathogenic mechanisms remain elusive. Currently, effective therapeutic targets and treatment methods for this disease are still lacking. This study tried to explore the pathogenic mechanisms of IPF. We found elevated expression of SULF1 in lung tissues of IPF patients compared to normal control lung tissues. SULF1 is an enzyme that modifies heparan sulfate chains of heparan sulfate proteoglycans, playing a critical role in biological regulation. However, the effect of SULF1 in pulmonary fibrosis remains incompletely understood. Our study aimed to investigate the impact and mechanisms of SULF1 in fibrosis. METHODS: We collected lung specimens from IPF patients for transcriptome sequencing. Validation of SULF1 expression in IPF patients was performed using Western blotting and RT-qPCR on lung tissues. ELISA experiments were employed to detect SULF1 concentrations in IPF patient plasma and TGF-ß1 levels in cell culture supernatants. We used lentiviral delivery of SULF1 shRNA to knock down SULF1 in HFL1 cells, evaluating its effects on fibroblast secretion, activation, proliferation, migration, and invasion capabilities. Furthermore, we employed Co-Immunoprecipitation (Co-IP) to investigate the regulatory mechanisms involved. RESULTS: Through bioinformatic analysis of IPF transcriptomic sequencing data (HTIPF) and datasets GSE24206, and GSE53845, we identified SULF1 may potentially play a crucial role in IPF. Subsequently, we verified that SULF1 was upregulated in IPF and predominantly increased in fibroblasts. Furthermore, SULF1 expression was induced in HFL1 cells following exposure to TGF-ß1. Knockdown of SULF1 suppressed fibroblast secretion, activation, proliferation, migration, and invasion under both TGF-ß1-driven and non-TGF-ß1-driven conditions. We found that SULF1 catalyzes the release of TGF-ß1 bound to TGFßRIII, thereby activating the TGF-ß1/SMAD pathway to promote fibrosis. Additionally, TGF-ß1 induces SULF1 expression through the TGF-ß1/SMAD pathway, suggesting a potential positive feedback loop between SULF1 and the TGF-ß1/SMAD pathway. CONCLUSIONS: Our findings reveal that SULF1 promotes fibrosis through the TGF-ß1/SMAD pathway in pulmonary fibrosis. Targeting SULF1 may offer a promising therapeutic strategy against IPF.

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles.

We describe herein a facile method to access 2,3-epoxyesters with fluorine-containing substituents at their 3-position starting from the corresponding enoates by utilization of the low-costed and easy-to-handle reagent, NaOCl·5H2O. Because very little has been disclosed about the reactivity of such 2,3-epoxyesters, their epoxy ring opening by a variety of nucleophiles was carried out and we succeeded in clarifying these chemo- as well as regioselective processes proceeding via the SN2 mechanism to mainly afford 2-substituted 3-hydroxyesters usually in a highly anti selective manner.

Metallo-ß-lactamase-producing Pseudomonas aeruginosa Isolates from Two Tertiary Care Centres in a District of Nepal: A Descriptive Cross-sectional Study.

INTRODUCTION: Pseudomonas aeruginosa isolates producing metallo-ß-lactamase have caused nosocomial outbreaks, severe infections, and ineffective carbapenem therapy worldwide since 1991. Due to their prevalence, hospital infection control techniques are difficult. This study aimed to find out the prevalence of metallo-ß-lactamase among P. aeruginosa isolates from two tertiary care hospitals in Kathmandu. METHODS: A descriptive cross-sectional study was conducted at the Department of Microbiology and Department of Pathology of two tertiary care centres in Kathmandu from 7 December 2021 to 6 April 2023, after receiving ethical approval from the Ethical Review Board. Isolated strains were identified and tested for antibiotic susceptibility by modified Kirby-Bauer Methods. Metallo-ß-lactamase presence was confirmed using an imipenem-imipenem/ ethylenediaminetetraacetic acid disc. A convenience sampling method was used. The point estimate was calculated at 95% Confidence Interval. RESULTS: Among 255, Pseudomanas aeruginosa isolates, the distribution of metallo-ß-lactamase-producing Pseudomanas aeruginosa was 103 (40.39%) (34.32-46.69 at 95% Confidence Interval). Multidrug resistance categories included multidrug resistance 74 (71.80%), extensively drug resistance 32 (31.10%), P. aeruginosa difficult-to-treat 16 (15.53%) and carbapenem-resistant P. aeruginosa was determined to be 82 (79.60%). CONCLUSIONS: The study found a high prevalence of metallo-ß-lactamase-producing Pseudomanas aeruginosa isolates, requiring early identification, infection control measures, and an all-inclusive antimicrobial therapy protocol to reduce their spread in medical settings.

Engineered 3D human neurovascular model of Alzheimer's disease to study vascular dysfunction.

The blood-brain barrier (BBB) serves as a selective filter that prevents harmful substances from entering the healthy brain. Dysfunction of this barrier is implicated in several neurological diseases. In the context of Alzheimer's disease (AD), BBB breakdown plays a significant role in both the initiation and progression of the disease. This study introduces a three-dimensional (3D) self-assembled in vitro model of the human neurovascular unit to recapitulate some of the complex interactions between the BBB and AD pathologies. It incorporates primary human brain endothelial cells, pericytes and astrocytes, and stem cell-derived neurons and astrocytes harboring Familial AD (FAD) mutations. Over an extended co-culture period, the model demonstrates increased BBB permeability, dysregulation of key endothelial and pericyte markers, and morphological alterations mirroring AD pathologies. The model enables visualization of amyloid-beta (Aß) accumulation in both neuronal and vascular compartments. This model may serve as a versatile tool for neuroscience research and drug development to provide insights into the dynamic relationship between vascular dysfunction and AD pathogenesis.

In vitro ß-hydroxybutyrate stability evaluation in femoral blood and vitreous humor for integration into forensic toxicology practices.

Thanatological biochemistry has gained prominence in determining causes of death, especially when suspected fatal pathologies do not exhibit clear postmortem macroscopic and/or microscopic features, such as in cases of ketoacidosis. Indeed, in these cases, the measurement of ß-hydroxybutyrate (BHB) in femoral blood and/or vitreous humor is of particular importance. However, data on its in vitro stability remain scarce, especially in vitreous humor. In this context, the study reported here aims to assess the in vitro stability of BHB. BHB quantification was performed using a liquid chromatography coupled with tandem mass spectrometry method. To investigate BHB stability, two different postmortem matrices were considered: femoral blood and vitreous humor. These matrices were pooled, aliquoted and spiked with BHB at three different concentrations (50 mg/L, 100 mg/L, and 200 mg/L; n = 3). Initial BHB concentrations were established on day 1. Each sample was then divided into two aliquots for storage under two conditions: 20 °C and 4 °C. Analyses were performed on Day 3, 7, 14, and 28. The study revealed no significant degradation of BHB in femoral blood or vitreous humor over time (days 1-28), confirming the robustness and reliability of BHB measurement in these matrices as a postmortem biomarker of ketoacidosis under the tested temperature conditions (+4 °C or -20 °C). These results support a systematic integration of BHB measurement into the routine workflow of forensic toxicology laboratories.

Unveiling the interplay of MAPK/NF-κB/MLKL axis in brain health: Omega-3 as a promising candidates against copper neurotoxicity.

Excessive intake of copper (Cu) may lead to increased inflammatory responses in brain, which can cause damage to neurons and glial cells, thereby affecting normal brain function. Omega-3 (ω-3) is a common dietary supplement, particularly rich in DHA in the brain, known for its anti-inflammatory properties and its role in lipid balance regulation and structural maintenance. Here, ω-3 is supplemented to Cu-exposed chickens to assess its neuroprotection in vivo and in vitro. Pathologically, ω-3 significantly alleviated structural and functional abnormalities in brain under excess Cu, including barrier disruption, neuronal shrinkage necroptosis and increased release of inflammatory factors such as IL-1ß. The molecular docking analyses unveiled high enrichment values of inflammation and MAPK pathway, with IL-1ß gene enrichment the highest value. Mechanistically, DHA stabilized the active site of IL-1ß, thereby reducing the activation of NF-κB signal and phosphorylation of MAPK/MLKL cascades, ultimately mitigating Cu-induced inflammatory effects. These mechanisms elucidate the action mode of Cu neurotoxicity from aspect of MAPK/NF-κB/MLKL axis and the promising neuroprotection of ω-3.

Pharmacological upregulation of macrophage-derived itaconic acid by pubescenoside C attenuated myocardial ischemia-reperfusion injury.

INTRODUCTION: Myocardial ischemia-reperfusion injury (MIRI) remains a prevalent clinical challenge globally, lacking an ideal therapeutic strategy. Macrophages play a pivotal role in MIRI pathophysiology, exhibiting dynamic inflammatory and resolutive functions. Macrophage polarization and metabolism are intricately linked to MIRI, presenting potential therapeutic targets. Pubescenoside C (PBC) from Ilex pubescens showed significantly anti-inflammatory effects, however, the effect of PBC on MIRI is unknown. OBJECTIVES: This study aimed to assess the cardioprotective effects of PBC against MIRI and elucidate the underlying mechanisms. METHODS: Sprague-Dawley rats, H9c2 and RAW264.7 macrophages were used to establish the in vitro and in vivo models of MIRI. TTC/Evans blue staining, immunohistochemical staining, metabonomics analysis, chemical probe, surface plasmon resonance (SPR), co-immunoprecipitation (CO-IP) assays were used for pharmacodynamic and mechanism study. RESULTS: PBC administration effectively reduced myocardial infarct size, decreased ST-segment elevation, and lowered CK-MB levels, concurrently promoting macrophage M2 polarization in MIRI. Furthermore, PBC-treated macrophages and their conditioned culture medium attenuated the apoptosis of H9c2 cells induced by oxygen-glucose deprivation/reoxygenation (OGD/R). Metabonomics analysis revealed that PBC increased the production of itaconic acid (ITA) and malic acid (MA) in macrophages, which conferred protection against OGD/R injury in H9c2 cells. Mechanistic investigations indicated that ITA exerted its effects by covalently modifying pyruvate kinase M2 (PKM2) at Cys474, Cys424, and Lys151, thereby facilitating PKM2's mitochondrial translocation and enhancing the PKM2/Bcl2 interaction, subsequently leading to decreased degradation of Bcl2. SPR assays further revealed that PBC bound to HSP90, facilitating the interaction between HSP90 and GSK3ß and resulting in the inactivation of GSK3ß activity and upregulation of key metabolic enzymes for ITA and MA production (Acod1 and Mdh2). CONCLUSION: PBC alleviates MIRI-induced cardiomyocyte apoptosis by modulating the HSP90/ITA/PKM2 axis. Furthermore, pharmacological upregulation of ITA emerges as a promising therapeutic approach for MIRI, hinting at PBC's potential as a candidate drug for MIRI therapy.

In isolated brown adipose tissue mitochondria UCP1 is not essential for nor involved in the uncoupling effects of the classical uncouplers FCCP and DNP.

Recent patch-clamp studies of mitoplasts have challenged the traditional view that classical chemical uncoupling (by e.g. FCCP or DNP) is due to the protonophoric property of these substances themselves. These studies instead suggest that in brown-fat mitochondria, FCCP- and DNP-induced uncoupling is mediated through activation of UCP1 (and in other tissues by activation of the adenine nucleotide transporter). These studies thus advocate an entirely new paradigm for the interpretation of standard bioenergetic experiments. To examine whether these patch-clamp results obtained in brown-fat mitoplasts are directly transferable to classical isolated brown-fat mitochondria studies, we investigated the effects of FCCP and DNP in brown-fat mitochondria from wildtype and UCP1 KO mice, comparing the FCCP and DNP effects with those of a fatty acid (oleate), a bona fide activator of UCP1. Whereas the sensitivity of brown-fat mitochondria to oleate was much higher in UCP1-containing than in UCP1 KO mitochondria, there was no difference in sensitivity to FCCP and DNP between these mitochondria, neither in oxygen consumption rate nor in membrane potential studies. Correspondingly, the UCP1-dependent ability of GDP to competitively inhibit activation by oleate was not seen with FCCP and DNP. It would thus be premature to abandon the established bioenergetic interpretation of chemical uncoupler effects in classical isolated brown-fat mitochondria-and probably also generally in this type of mitochondrial study. Understanding the molecular and structural reasons for the different outcomes of mitoplast and mitochondrial studies is a challenging task in bioenergetics.

Anti-inflammatory and Restorative effects of milk exosomes and Dexamethasone-Loaded exosomes in a corneal alkali burn model.

Corneal alkali burn is a common and challenging ocular trauma, necessitating the use of dexamethasone (DXMS) as a therapeutic agent. However, prolonged and frequent administration of this drug can lead to undesirable side effects, limiting its clinical application. This study aimed to investigate the role and mechanism of action of exosomes as drug carriers in corneal alkali burn repair. We employed centrifugation to isolate milk exosomes (EXO) as nanocarriers. We observed that EXO enhanced the activity and migration of corneal epithelial cells, expediting the repair process following corneal injury. Additionally, a nano-drug delivery model (DXMS@EXO) was designed using ultrasound to load DXMS into exosomes, thus enabling targeted delivery to inflammatory cells and enhancing drug efficacy. DXMS@EXO inhibited the inflammatory processes in the corneal alkali burn model by modulating the classical Wnt signaling pathway, thereby promoting corneal re-epithelialization and wound healing and accelerating the repair process of corneal alkali burn. Neither EXO nor DXMS@EXO exhibited significant side effects during the course of treatment. This study highlighted the substantial potential of EXO and DXMS@EXO in improving drug efficacy and facilitating the repair of corneal alkali burn.

Biomimetic Aramid Nanofiber/ß-FeOOH Composite Coating for Polypropylene Separators in Lithium-Sulfur Batteries.

Aramid nanofibers (ANFs), with attractive mechanical and thermal properties, have attracted much attention as key building units for the design of high-performance composite materials. Although great progress has been made, the potential of ANFs as fibrous protein mimetics for controlling the growth of inorganic materials has not been fully revealed, which is critical for avoiding phase separation associated with typical solution blending. In this work, we show that ANFs could template the oriented growth of ß-FeOOH nanowhiskers, which enables the synthesis of ANFs/ß-FeOOH hybrids as composite coatings for polypropylene (PP) separators in Li-S batteries. The modified PP separator exhibits enhanced mechanical properties, heightened thermal performance, optimized electrolyte wettability, and improved ion conductivity, leading to superior electrochemical properties, including high initial specific capacity, better rate capability, and long cycling stability, which are superior to those of the commercial PP separators. Importantly, the addition of ß-FeOOH to ANFs could further contribute to the suppression of lithium polysulfide shuttling by chemical immobilization, inhibition of the growth of lithium dendrites because of the intrinsic high modulus and hardness, and promotion of reaction dynamics due to the catalytic effect. We believe that our work may provide a potent biomimetic pathway for the development of advanced battery separators based on ANFs.

Colchicine effect on biomarkers of cardiac remodelling and atherosclerosis in ST-elevation myocardial infarction: A randomized controlled trial.

AIMS: Owing to its underlying inflammatory nature, atherosclerotic cardiovascular disease remains the leading global cause of mortality, particularly post-ST-elevation myocardial infarction (STEMI), a condition with significant risk for further cardiovascular events and mortality. This study aimed to investigate colchicine's effect on inflammation, cardiac remodelling and atherosclerotic risk in STEMI patients. METHODS: We conducted a randomized controlled study on 88 STEMI patients undergoing percutaneous coronary intervention. Eligible patients were randomly assigned to 1 of 2 groups. The control group received the guideline-directed medical therapy for STEMI, and the test group received guideline-directed medical therapy and 0.5 mg colchicine twice daily for 3 months. The soluble suppressor of tumorigenicity (sST2), interleukin-1ß, lipid profile parameters, triglyceride (TG)/high-density lipoprotein (HDL-C) ratio levels and left ventricular ejection fraction were evaluated for patients at baseline and the end of the 3 months. RESULTS: No significant effects were reported for colchicine on sST2, interleukin-1ß levels or left ventricular ejection fraction. Colchicine significantly lowered TG levels vs. controls, 134 (46-353) vs. 176 (72-825) respectively, P = .02, as well as TG/HDL-C ratio levels, 4.16 (2.75-5.24) vs. 5.11 (3.51-8.33),` respectively, P = .024. sST2 levels of the studied cohort were positively correlated with their TG/HDL-C ratio levels (R = .459, P < .001) at the end of follow-up. CONCLUSION: Our study highlights a promising impact of colchicine on atherosclerosis and cardiac remodelling factors in STEMI patients. Colchicine significantly reduced TG levels and TG/HDL-C ratio and was safe and well tolerated. Larger long-term studies powered to assess clinical outcomes of remodelling are necessary to confirm its beneficial effects in STEMI. GOV REGISTRATION ID: NCT06054100.