Schisandra chinensis lignans improve insulin resistance by targeting TLR4 and activating IRS-1/PI3K/AKT and NF-κB signaling pathways.

Schisandra chinensis, a traditional Chinese medicine, has been widely applied in China to treat diabetes and its complications. The aim of this study was to discover the active compounds and explain related molecular mechanism contributing to the anti-diabetic effect of Schisandra chinensis. Herein, the therapeutic effects of Schisandra chinensis extracts on type 2 diabetes mellitus (T2DM) were firstly confirmed in vivo. Subsequently, various lignans were isolated from Schisandra chinensis and tested for hypoglycemic activity in palmitic acid-induced insulin-resistant HepG2 (IR-HepG2) cells. Among these lignans, R-biar-(7S,8R)-6,7,8,9-tetrahydro-1,2,3,12,13,14-hexamethoxy-7,8-dimethyl-7-dibenzo [a, c] cyclooctenol (compound 2) and Gomisin A (compound 4) were identified significantly increased the glucose consumption in IR-HepG2 cells. Meanwhile, compounds 2 and 4 activated the insulin receptor substrate-1 (IRS-1)/phosphoinositide 3-kinase (PI3K)/Ak strain transforming (AKT) pathway, which regulates glucose transporter 2 (GLUT2) and glucose-6-phosphatase (G6Pase), essential for gluconeogenesis and glucose uptake. These compounds also inhibited the nuclear factor-κB (NF-κB) signaling pathway, reducing interleukin-6 (IL-6) levels. Importantly, the hypoglycemic effects of compounds 2 and 4 were diminished after Toll-like receptor 4 (TLR4) knockdown. Cellular thermal shift assays confirmed increased TLR4 protein stability upon treatment with these compounds, indicating direct binding to TLR4. Furthermore, TLR4 knockdown reversed the effects of compounds 2 and 4 on the NF-κB and IRS-1/PI3K/AKT pathways. Taken together, compounds 2 and 4 alleviate IR by targeting TLR4, thereby modulating the NF-κB and IRS-1/PI3K/AKT pathways. These findings suggest that compounds 2 and 4 could be developed as therapeutic agents for T2DM.

Cross-sectional comparison of the association between three different insulin resistance surrogates and frailty: NHANES 1999-2018.

Background: The correlation between various insulin resistance surrogates and frailty remains under investigation in the scientific community. Methods: Data from NHANES (1999-2018) were used. We utilized weighted binary logistic regression, trend tests, RCS analysis, and subgroup analysis to comprehensively assess the link between METS-IR, HOMA-IR, and TyG, and frailty risk. Results: The results revealed a significant positive association between high levels of METS-IR, HOMA-IR, and TyG with the risk of frailty in all models. Notably, in model 4, the highest quintile of METS-IR showed the strongest link (OR: 2.960, 95% CI: 2.219-3.949), with HOMA-IR (OR: 2.522, 95% CI: 1.927-3.301) following closely behind. Trend tests revealed a positive trend between METS-IR, HOMA-IR, and TyG with the risk of frailty (P for trend < 0.05). RCS analysis showed a linear relationship between METS-IR and the risk of frailty (P for nonlinearity > 0.05). In contrast, HOMA-IR and TyG exhibited a U-shaped nonlinear relationship (P for nonlinearity < 0.05). Conclusion: The research identified a linear association between METS-IR and frailty risk, whereas HOMA-IR and TyG displayed a U-shaped, nonlinear relationship pattern with the risk of frailty. Among the varying levels examined, the linkage between METS-IR and frailty was most pronounced in the top quintile.

Role of growth temperature on microstructural and electronic properties of rapid thermally grown MoTe2 thin film for IR detection.

In the field of electronic and optoelectronic applications, two-dimensional materials are found to be the promising candidates for futuristic devices. For the detection of infrared light, MoTe2 possesses an appropriate bandgap for which p-MoTe2/n-Si heterojunctions are suits well for photodetectors. In this study, rapid thermal technique is used to grow MoTe2 thin films on silicon (Si) substrates. Molybdenum (Mo) thin films were deposited using sputtering system on Si substrate and Tellurium (Te) film was deposited on Mo film by thermal evaporation technique. The substrates with Mo/Te thin films are kept in a face-to-face manner inside the RTP furnace. The growth was carried out at a base pressure of 2 torr with the flow of 160 sccm argon gas at different temperatures ranging from 400 °C to 700 °C. The XRD peaks appeared around 2θ = 12.8°, 25.5°, 39.2°, 53.2° corresponding to (002), (004), (006) and (008) orientation of hexagonal 2H-MoTe2 structure. The characteristic Raman peaks of MoTe2,observed at ~119 cm-1 and ~172 cm-1,corresponds to in-plane E1g and out-of-plane A1g mode of MoTe2, whereas the prominent peaks of the in-plane E12g mode at ∼234 cm-1, and the out-of-plane B12g mode at ∼289 cm-1 are also observed. RMS roughness is found to be increasing with increasing growth temperature. The bandgap of MoTe2 is calculated using Tauc plot and found to be 0.91 eV. Electrical characterizations are carried out using current-voltage and current-time measurement, where the maximum responsivity and detectivity are found to be 127.37 mA/W and 85.21 × 107 Jones for growth temperature of 600 °C and IR wavelength illumination of 1060 nm. .

Folic Acid as a Potential Vitamin in Glycemic Control: A Systematic Review.

PURPOSE: This systematic review aims to examine the relationship between serum folate level and folic acid supplements with glycemic control parameters (fasting blood glucose (FBG), insulin level, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and Hemoglobin A1C (HbA1c)) in adult individuals with current studies. METHODS: In this study, which was designed as a systematic review, the searches were performed on Web of Science, Science Direct, Medline, Wiley, and Cochrane Library databases between April 10, 2023, and May 10, 2023, and the searches were updated between October 16, 2023, and November 14, 2023. Of the 1855 studies obtained from the screening, 17 met the criteria and were included in the systematic review. The PROSPERO system registered the study protocol (ID: CRD42023472434). RECENT FINDINGS: Although no significant correlation was found between serum folate levels and glycemic control parameters in most of the cross-sectional studies included in this systematic review, most of the randomized controlled trials showed that glycemic control parameters (FBG, insulin, HOMA-IR) decreased significantly in the intervention group receiving folic acid supplementation compared to the control group. However, study durations were short, and HbA1c needed to be evaluated in most studies. This makes it difficult to get information about the long-term effects of folic acid supplementation. More comprehensive studies should be conducted to draw more precise conclusions about the relationship between folic acid levels and folic acid supplementation with glycemic control parameters.

Mixed reality-supported near-infrared photoimmunotherapy for oropharyngeal cancer: a case report.

Introduction and importance: Near-infrared photoimmunotherapy (NIR-PIT, Alluminox) uses an antibody-photoabsorber conjugate and light excitation, requiring precise illumination. Mixed reality (MR) technology can enhance medical procedures through advanced visualization and planning. Case presentation: An 86-year-old man with recurrent oropharyngeal cancer and right cervical metastasis received NIR-PIT. Three-dimensional models from computed tomography (CT) and FDG-PET/CT images were used as holograms on a head-mounted display (HMD) for precise light targeting. Clinical discussion: HMD-MR technology was utilized for preoperative simulation and guided ideal light direction during surgery. This improved the effectiveness of NIR-PIT. Conclusion: Three months post-treatment, no residual lesion was observed, demonstrating the utility of HMD-MR technology in optimizing NIR-PIT outcomes.

Key subdomains of mesencephalic astrocyte-derived neurotrophic factor attenuate myocardial ischemia/reperfusion injury by JAK1/STAT1/NF-κB signaling pathway.

BACKGROUND: Myocardial ischemia/reperfusion (I/R) injury is a common pathological process in clinical practice. Developing effective therapeutic strategies to reduce or prevent this injury is crucial. The article aimed to investigate the role and mechanism of mesencephalic astrocyte-derived neurotrophic factor (MANF) and its key subdomains in modulating myocardial I/R-induced cardiomyocyte apoptosis. METHODS: MANF stable knockout cell line and MANF mutant overexpression plasmids were constructed. The effects of MANF and mutants on apoptosis and endoplasmic reticulum (ER) stress related proteins were evaluated in hypoxia/reoxygenation-induced HL-1 cardiomyocytes by western blot, immunofluorescence, Tunel and flow cytometry. Echocardiography, ELISA, TTC and Masson were used to observe the effects of recombinant MANF protein (rMANF) on cardiac function in myocardial I/R mice. RESULTS: This study observed increased expression of MANF in both myocardial infarction patients and I/R mice. MANF overexpression in cardiomyocytes decreased ER stress-induced apoptosis, while MANF knockout exacerbated it. rMANF improved cardiac function in I/R mice by reducing injury and inflammation. This study specifically demonstrates that mutations in the α-helix of MANF were more effective in reducing ER stress and cardiomyocyte apoptosis. Mechanistically, MANF and the α-helix mutant attenuated I/R injury by inhibiting the JAK1/STAT1/NF-κB signaling pathway in addition to reducing ER stress-induced apoptosis. CONCLUSION: These findings highlight MANF and its subdomains as critical regulators of myocardial I/R injury, offering promising therapeutic targets with significant clinical implications for I/R-related diseases.

Combining Fourier-transform infrared spectroscopy and multivariate analysis for chemotyping of cell wall composition in Mungbean (Vigna radiata (L.) Wizcek).

BACKGROUND: Dissection of complex plant cell wall structures demands a sensitive and quantitative method. FTIR is used regularly as a screening method to identify specific linkages in cell walls. However, quantification and assigning spectral bands to particular cell wall components is still a major challenge, specifically in crop species. In this study, we addressed these challenges using ATR-FTIR spectroscopy as it is a high throughput, cost-effective and non-destructive approach to understand the plant cell wall composition. This method was validated by analysing different varieties of mungbean which is one of the most important legume crops grown widely in Asia. RESULTS: Using standards and extraction of a specific component of cell wall components, we assigned 1050-1060 cm-1 and 1390-1420 cm-1 wavenumbers that can be widely used to quantify cellulose and lignin, respectively, in Arabidopsis, Populus, rice and mungbean. Also, using KBr as a diluent, we established a method that can relatively quantify the cellulose and lignin composition among different tissue types of the above species. We further used this method to quantify cellulose and lignin in field-grown mungbean genotypes. The ATR-FTIR-based study revealed the cellulose content variation ranges from 27.9% to 52.3%, and the lignin content variation ranges from 13.7% to 31.6% in mungbean genotypes. CONCLUSION: Multivariate analysis of FT-IR data revealed differences in total cell wall (600-2000 cm-1), cellulose (1000-1100 cm-1) and lignin (1390-1420 cm-1) among leaf and stem of four plant species. Overall, our data suggested that ATR-FTIR can be used for the relative quantification of lignin and cellulose in different plant species. This method was successfully applied for rapid screening of cell wall composition in mungbean stem, and similarly, it can be used for screening other crops or tree species.

Leveraging Supervised Machine Learning Algorithms for System Suitability Testing of Mass Spectrometry Imaging Platforms.

Quality control and system suitability testing are vital protocols implemented to ensure the repeatability and reproducibility of data in mass spectrometry investigations. However, mass spectrometry imaging (MSI) analyses present added complexity since both chemical and spatial information are measured. Herein, we employ various machine learning algorithms and a novel quality control mixture to classify the working conditions of an MSI platform. Each algorithm was evaluated in terms of its performance on unseen data, validated with negative control data sets to rule out confounding variables or chance agreement, and utilized to determine the necessary sample size to achieve a high level of accurate classifications. In this work, a robust machine learning workflow was established where models could accurately classify the instrument condition as clean or compromised based on data metrics extracted from the analyzed quality control sample. This work highlights the power of machine learning to recognize complex patterns in MSI data and use those relationships to perform a system suitability test for MSI platforms.

Naringin Affects Caspase-3, IL-1ß, and HIF-1α Levels in Experimental Kidney Ischemia-reperfusion in Rats.

BACKGROUND: Microvascular dysfunction develops in tissues after Ischemia-Reperfusion (I/R). The current study aimed to determine the effect of naringin supplementation on kidney caspase-3, IL-1ß, and HIF-1α levels and kidney histology in rats undergoing unilateral nephrectomy and kidney-ischemia reperfusion. METHODS: The study was conducted on 8-12 weeks old 40 Wistar-type male rats. Experimental renal ischemia- reperfusion and unilateral nephrectomy were performed under general anesthesia in rats. Experimental groups were formed as follows: 1-Control group, 2-Sham control + Vehicle group, 3- Renal ischemia-reperfusion (Renal I+R) + Vehicle group, 4-Renal I+R + Naringin (50 mg/kg/day) group (3 days application) group, 5-Renal I+R + Naringin (100 mg/kg/day) group (3 days supplementation). Nephrectomy in the left kidneys and the ischemia for 45 minutes and reperfusion in the right kidneys followed by 72 hours of reperfusion. Naringin was administered intraperitoneally at the beginning of the reperfusion, 24 hours and 48 hours later. At the end of the experiments, blood was first taken from the heart in animals under general anesthesia. Then, the animals were killed by cervical dislocation, and kidney tissue samples were taken. Tissues were evaluated for caspase-3, IL-1ß, and HIF-1α as well as histologically. RESULTS: As a result of ischemia in kidney tissues, HIF-1α decreased, while caspase-3 and IL-1ß increased. I/R also caused damage to the kidney tissue. However, naringin supplementation corrected the deterioration to a certain extent. CONCLUSION: The results of the study showed that naringin may have protective effects on kidney damage due to anti-inflammatory and antiapoptosis mechanisms caused by unilateral nephrectomy and I/R in rats.

Gold(III) complexes with chloride and cyanopyridines: Facilitated hydrolysis of nitrile ligand to amide and antibacterial activity.

A range of novel simple gold(III) compounds has been synthesized in their monocrystalline form, including two previously unknown chloro-complexes of Au3+ with 2-cyanopyridine or 3-cyanopyridine, respectively. Our investigations have revealed the intricate nature of the reaction between 2-cyanopyridine and tetrachloroauric acid, yielding at least three distinct products. The main product, obtained in high yield, is a salt featuring a tetrachloroauric anion and a pyridinium cation stabilized by a hydrogen bond to a further 2-cyanopyridine molecule. Moreover, we observed the in-situ formation of a 2-cyanopyridine-AuCl3 complex, which undergoes hydrolysis of the nitrile bond to yield a picolinamide-Au(III) complex. The complexes were characterized by IR and Raman spectroscopies, NMR spectroscopy, and single-crystal XRD studies. Additional computational studies were conducted to explain unusual spectral features, the observed disparities in the complexation reactions of the three isomeric cyanopyridine ligands and the distinct reactivity of the complex with 2-cyanopyridine. Based on these studies, we propose a mechanism for the catalyzed hydrolysis of the nitrile bond within the Au(III) complex. Finally, we assessed the antimicrobial efficacy of the synthesized gold(III) complexes against a spectrum of bacteria and fungi.

Nanoscale Structural Characterization of Amyloid ß 1-42 Oligomers and Fibrils Grown in the Presence of Fatty Acids.

Mono- and polyunsaturated fatty acids (FAs) are broadly used as food supplements. However, their effect on the aggregation of amyloidogenic proteins remains unclear. In this study, we investigated the effect of a large number of mono- and polyunsaturated, as well as fully saturated FAs on the aggregation of amyloid ß1-42 (Aß1-42) peptide. A progressive aggregation of this peptide is the expected molecular cause of Alzheimer's disease (AD), one of the most common neurodegenerative pathologies in the world. We found that arachidonic and stearic acids delayed the aggregation of Aß1-42. Using Nano-Infrared spectroscopy, we found that FAs caused very little if any changes in the secondary structure of Aß1-42 oligomers and fibrils formed at different stages of protein aggregation. However, the analyzed mono- and polyunsaturated, as well as fully saturated FAs uniquely altered the toxicity of Aß1-42 fibrils. We found a direct relationship between the degree of FAs unsaturation and toxicity of Aß1-42 fibrils formed in their presence. Specifically, with an increase in the degree of unsaturation, the toxicity Aß1-42/FA fibrils increased. These results indicate that fully saturated or monounsaturated FAs could be used to decrease the toxicity of amyloid aggregates and, consequently, decelerate the development of AD.

Investigation of Neighboring Group Participation in 3,4-Diacetylated Glycosyl Donors in the Gas Phase.

A key challenge in oligosaccharide synthesis is the stereoselective installation of glycosidic bonds. Each glycosidic linkage has one of two possible stereo-chemical geometries, α/ß or 1,2-cis/trans. An established approach to install 1,2-trans glycosidic bonds is neighboring group participation (NGP), mediated by a 2-O-acyl group. Extension of this intramolecular stabilization to nucleophilic groups located at more remote positions has also been suggested, but remains poorly understood. Previously, we employed infrared ion spectroscopy to characterize the molecular ions of monoacetylated sugar donors and showed how the strength of the stabilizing effect depends on the position of the participating ester group on the glycosyl donor ring as well as on its relative stereochemistry. In this work, we investigated glycosyl donors carrying two acyl groups. Using isotope labelling and isomer population analysis we were able to resolving spectra of isomeric mixtures and establish the relative contribution of individual species. We conclude that 3,4-diacetyl mannosyl donors exclusively form a dioxanium ion as a result of C-3 acyl stabilization. In contrast, the glucosyl and galactosyl cations form mixtures of C-3 and C-4 acyl participation products. Hence, the combination of isotope labeling and population analysis allows for the study of increasingly complex glycosyl cations.

A nondestructive technique for the sex identification of third instar Cochliomyia macellaria larvae.

Forensic entomology plays an important role in medicolegal investigations by using insects, primarily flies, to estimate the time of colonization. This estimation relies on the development of the flies found at the (death) scene and can be affected (and sometimes corrected) by external factors, such as temperature and humidity, and internal factors, such as species and sex. This study leverages infrared (IR) spectroscopy combined with machine learning models-Partial Least Squares Discriminant Analysis (PLS-DA) and eXtreme Gradient Boosting trees Discriminant Analysis (XGBDA)-to differentiate between male and female Cochliomyia macellaria larvae, commonly found on human remains. Significant vibrational differences were detected in the infrared spectra of third instar C. macellaria larvae, with distinct peaks showing variations in relative absorbance between sexes, suggesting differences in biochemical compositions such as cuticular proteins and lipids. The application of PLS-DA and XGBDA yielded high classification accuracies of about 94% and 96%, respectively, with female spectra consistently having higher sensitivity than males. This non-destructive approach offers the potential to refine supplemental post-mortem interval estimations significantly, enhancing the accuracy of forensic analyses.

Molecular Probe with Potential for Combined Boron Neutron Capture and Photothermal Antitumor Therapy.

Both boron neutron capture therapy (BNCT) and photothermal therapy (PTT) have been applied to tumor treatment in clinical. However, their therapeutic efficacy is limited. For BNCT, the agents not only exhibit poor targeting ability but also permit only a single irradiation session within a course due to significant radiation risks. In the context of PTT, despite enhanced selectivity, the limited photothermal effect fails to meet clinical demands. Hence, the imperative arises to combine these two therapies to enhance tumor-killing capabilities and improve the targeting of BNCT agents by leveraging the advantages of PTT agents. In this study, we synthesized a potential responsive agent by linking 4-mercaptophenylboronic acid (MPBA) and IR-780 dye that served as the agents for BNCT and PTT, respectively, which possesses the dual capabilities of photothermal effects and thermal neutron capture. Results from both in vitro and in vivo research demonstrated that IR780-MPBA effectively inhibits tumor growth through its photothermal effect with no significant toxicity. Furthermore, IR780-MPBA exhibited substantial accumulation in tumor tissues and superior tumor-targeting capabilities compared with MPBA, which demonstrated that IR780-MPBA possesses significant potential as a combined antitumor therapy of PTT and BNCT, presenting a promising approach for antitumor treatments.

Functional characterization and biotechnological applications of exopolysaccharides produced by newly isolated Enterococcus hirae MLG3-25-1.

This study investigated the potential applications of Enterococcus hirae MLG3-25-1 exopolysaccharides (EPS), with a focus on their isolation, identification, production, and functional characteristics. After the bacterial strain was cultured in De Man-Rogosa-Sharpe (MRS) medium containing 1% glucose at 37 °C, the EPS was refined, and the highest yield of 0.85 mg/mL was achieved at the 24-h incubation period. Enterococcus hirae MLG3-25-1 was found to be able to produce EPS. The study explored the microstructure of the EPS, which resembles polysaccharide sheets with smooth surfaces, through scanning electron microscope (SEM) analysis. Through Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) analysis, the chemical composition, aligning with glycosidic bond characteristics, has been deciphered. Furthermore, the antimicrobial and antibiofilm activities against pathogenic bacteria, particularly Bacillus sp., demonstrated potential applications in combating antibiotic resistance. The EPS exhibited notable antioxidant activity (89.36% DPPH scavenging), along with high water-holding capacity (575%), emulsifying activity, and flocculation activity, suggesting its potential as a stabilizing agent in the food industry. Overall, this study provides a comprehensive characterization of Enterococcus hirae MLG3-25-1 EPS, emphasizing its diverse applications in antimicrobial, antioxidant, and food-related industries. These findings lay the groundwork for further exploration and utilization of this EPS in various sectors.

Value of interventional radiology and their contributions to modern medical systems.

Interventional radiology (IR) is a unique specialty that incorporates a diverse set of skills ranging from imaging, procedures, consultation, and patient management. Understanding how IR generates value to the healthcare system is important to review from various perspectives. IR specialists need to understand how to meet demands from various stakeholders to expand their practice improving patient care. Thus, this review discusses the domains of value contributed to medical systems and outlines the parameters of success. IR benefits five distinct parties: patients, practitioners, payers, employers, and innovators. Value to patients and providers is delivered through a wide set of diagnostic and therapeutic interventions. Payers and hospital systems financially benefit from the reduced cost in medical management secondary to fast patient recovery, outpatient procedures, fewer complications, and the prestige of offering diverse expertise for complex patients. Lastly, IR is a field of rapid innovation implementing new procedural technology and techniques. Overall, IR must actively advocate for further growth and influence in the medical field as their value continues to expand in multiple domains. Despite being a nascent specialty, IR has become indispensable to modern medical practice.

Exploration of Sargassum wightii: Extraction, Phytochemical Analysis, and Antioxidant Potential of Polyphenol.

Background The marine environment, with its rich biodiversity and nutrient-dense ecosystems, offers immense potential for discovering novel pharmaceutical products. Sargassum wightii is a type of brown seaweed that is particularly abundant in sulfated polysaccharides and polyphenolic compounds. These compounds are renowned for their wide range of biological activities. The exploration of such marine resources is crucial for identifying new compounds that can be harnessed for pharmaceutical and nutraceutical applications. Aims and objectives The primary aim of this study is to explore the bioactive compounds present in S. wightii, with a specific focus on its polyphenolic content. Additionally, the study seeks to evaluate the antioxidant properties of the compound. By doing so, the research aims to contribute to the growing body of knowledge on marine bioresources and their potential health benefits. Methods S. wightii samples were collected from the Mandapam coastal region in Rameshwaram, India. The cleaned seaweed was transported to the laboratory, where it was further washed, shade-dried, and ground into a fine powder. The powdered seaweed was then subjected to extraction using four different solvents: n-hexane, dichloromethane, ethyl acetate, and methanol. Phytochemical analyses were conducted on these extracts to identify the presence of various bioactive compounds. The total phenolic content of the extracts was determined, and antioxidant activity was assessed using the phosphomolybdenum method. Functional groups present in the extracts were identified using Fourier Transform Infrared (FT-IR) spectroscopy. Results Among the solvents used, the methanol extract yielded the highest amount of crude extract. Phytochemical analysis revealed a variety of bioactive compounds, with the methanol extract showing a notable presence of polyphenols. The total phenolic content was measured at 1.25 ± 0.6 mg gallic acid equivalence (GAE)/g of extract. The antioxidant activity, assessed through the phosphomolybdenum method, demonstrated significant free radical scavenging capabilities with an IC50 (half maximal inhibitory concentration) value of 68.23 ± 3.5 µg/mL. FT-IR spectroscopy confirmed the presence of functional groups characteristic of polyphenols and other bioactive compounds. Conclusion The study highlights the significant potential of S. wightii as a source of bioactive compounds with substantial antioxidant properties. These findings emphasize the importance of marine algae in the development of pharmaceutical and nutraceutical products, showcasing S. wightii's promising role in health-related applications.

Insights on early response to acute heat shock of bovine mammary epithelial cells through a multimethod approach.

Heat stress is a significant challenge in dairy cattle herds, affecting milk production and quality, and generating important changes at the cellular level. Most in vitro research on heat shock (HS) effects on dairy cow mammary cells was focused on medium-long-term effects. In recent years, Fourier transform-infrared (FT-IR) micro-spectroscopy has been increasingly used to study the effects of several external stresses on different cell lines, down to the level of single cellular components, such as DNA/RNA, lipids, and proteins. In this study, the possible changes at the biochemical and molecular level induced by acute (30 min-2 h) HS in bovine mammary epithelial (BME-UV1) cells were investigated. The cells were exposed to different temperatures, thermoneutral (TN, 37 °C) and HS (42 °C), and FT-IR spectra were acquired to analyse the effects of HS on biochemical characteristics of BME-UV1 cellular components (proteins, lipids, and DNA/RNA). Moreover, cell viability assay, reactive oxygen species production, and mRNA expression of heat shock proteins (HSPA1A, HSP90AA1, GRP78, GRP94) and antioxidant genes (SOD1, SOD2) by RT-qPCR were also analysed. The FT-IR results showed a change already at 30 min of HS exposure, in the content of long-chain fatty acids, which probably acted as a response to a modification of membrane fluidity in HS cells compared with TN cells. After 2 h of HS exposure, modification of DNA/RNA activity and accumulation of aggregated proteins was highlighted in HS cells. The gene expression analyses showed the overexpression of HSPA1A and HSP90AA1 starting from 30 min up to 2 h in HS cells compared with TN cells. At 2 h of HS exposure, also the overexpression of GRP94 was observed in HS cells. Acute HS did not affect cell viability, reactive oxygen species level, and SOD1 and SOD2 gene expression of BME-UV1 cells. According to the results obtained, cells initiate early defence mechanisms in case of acute HS and probably this efficient response capacity may be decisive for tolerance to heat stress of dairy cattle.

Therapeutic effect of F127-folate@PLGA/CHL/IR780 nanoparticles on folate receptor-expressing cancer cells.

Theragnostic platforms, which integrate therapeutic and diagnostic capabilities, have gained significant interest in drug research because of to their potential advantages. This study reports the development of a novel multifunctional nanoparticle carrier system based on poly(ᴅ,ʟ-lactic-co-glycolic acid) (PLGA) for the targeted delivery of the chemotherapeutic agent chlorambucil (CHL) and the imaging agent IR780. The approach in this study incorporates Pluronic F127-folate onto the PLGA nanoparticles, which enables targeted delivery to folate receptor-expressing cancer cells. The F127-folate@PLGA/CHL/IR780 nanoparticles were formulated using a nanoprecipitation technique, resulting in small size, high homogeneity, and negative surface charge. Importantly, the folate-targeted nanoparticles demonstrated enhanced uptake and cytotoxicity in folate receptor-positive cancer cell lines (MCF-7 and HepG-2) compared to folate receptor-negative cells (HEK 293). Additionally, the F127-folate@PLGA/CHL/IR780 nanoparticles exhibited a lower IC50 value against cancer cells than non-targeted F127@PLGA/CHL/IR780 nanoparticles. These findings suggest that the developed F127-folate@PLGA/CHL/IR780 nanoparticles hold promise as a theragnostic system for targeted cancer therapy and diagnosis, leveraging the advantages of PLGA, folate targeting, and the integration of therapeutic and imaging agents.

Pyrazine-bridged polymetallic copper-iridium clusters.

Single crystals of the mol-ecular compound, {Cu20Ir6Cl8(C21H24N2)6(C4H4N2)3]·3.18CH3OH or [({Cu10Ir3}Cl4(IMes)3(pyrazine))2(pyrazine)]·3.18CH3OH [where IMes is 1,3-bis-(2,4,6-trimethylphen-yl)imidazol-2-yl-idene], with a unique heterometallic cluster have been prepared and the structure revealed using single-crystal X-ray diffraction. The mol-ecule is centrosymmetric with two {Cu10Ir3} cores bridged by a pyrazine ligand. The polymetallic cluster contains three stabilizing N-heterocyclic carbenes, four Cl ligands, and a non-bridging pyrazine ligand. Notably, the Cu-Ir core is arranged in an unusual shape containing 13 vertices, 22 faces, and 32 sides. The atoms within the trideca-metallic cluster are arranged in four planes, with 2, 4, 4, 3 metals in each plane. Ir atoms are present in alternate planes with an Ir atom featuring in the peripheral bimetallic plane, and two Ir atoms featuring on opposite sides of the non-adjacent tetra-metallic plane. The crystal contains two disordered methanol solvent mol-ecules with an additional region of non-modelled electron density corrected for using the SQUEEZE routine in PLATON [Spek (2015 ▸). Acta Cryst. C71, 9-18]. The given chemical formula and other crystal data do not take into account the unmodelled methanol solvent mol-ecule(s).