Search Results (200)

L-type Ca²⁺ channels, particularly Ca_V1.2, play a crucial role in cardiac excitation-contraction coupling and are known to exhibit mechanosensitivity. However, the mechanisms regulating their response to mechanical stress remain poorly understood. To investigate the mechanosensitivity and nitric oxide (NO)-dependent regulation of L-type Ca²⁺ channels in rat ventricular cardiomyocytes, we used RNA sequencing to assess isoform expression and whole-cell patch-clamp recordings to measure L-type Ca²⁺ current (I_Ca,L) under controlled mechanical and pharmacological conditions. RNA sequencing revealed predominant expression of Ca_V1.2 (TPM: 0.1170 ± 0.0075) compared to Ca_V1.3 (0.0021 ± 0.0002) and Ca_V1.1 (0.0002 ± 0.0002). Local axial stretch (6–10 μm) consistently reduced I_Ca,L in proportion to stretch magnitude. The NO donor SNAP (200 μM) had variable effects on basal I_Ca,L in unstretched cells (stimulatory, inhibitory, or biphasic) but consistently restored stretch-reduced I_Ca,L to control levels. Ascorbic acid (10 μM), which reduces S-nitrosylation, increased basal I_Ca,L and partially restored the reduction caused by stretch, implicating S-nitrosylation in channel regulation. The sGC inhibitor ODQ (5 μM) decreased I_Ca,L in both stretched and unstretched cells, indicating involvement of the NO–cGMP pathway. Mechanical stress modulates L-type Ca²⁺ channels through a complex interplay between S-nitrosylation and NO–cGMP signaling, with S-nitrosylation playing a predominant role in stretch-induced effects. This mechanism may represent a key component of cardiac mechanotransduction and could be relevant for therapeutic targeting in cardiac pathologies involving mechanically induced dysfunction. Full article

Anoplophora glabripennis, is one of the most devastating wood borers of many broad leaf trees. Our previous results indicated that antennae of A. glabripennis showed electroantennogram (EAG) responses to several host plant volatiles. However, the quantities of active compounds necessary to trigger an EAG response remains unclear. To relate EAG responses with quantities of active molecules, we quantified the level of molecular triggering in the EAG response of A. glabripennis by a series of procedures. First, we used the EAG apparatus to measure EAG responses of A. glabripennis to five concentrations of eight chemicals and obtained dose–response curves. Second, volatiles released after blowing air over filter paper loaded with volatiles for different numbers of times (purging) were collected by solid-phase microextraction (SPME) and quantified by gas chromatography (GC), so we obtained the quantity of chemical released from each purge; the minimum number of molecules in each purge in the EAG was calculated by the molar mass for different compounds. For instance, the number of molecules of (Z)-3-hexenol reaching the female antennal segment in EAG was 8.68 × 10⁸ at 0.01 ng/μL concentration, and 1.39 × 10⁵ at 0.01 mV potential value. Finally, by comparing sensilla numbers on tested antennal segments with the entire antennae, the minimum number of molecules, or molecular flow, of tested compounds required to elicit an electrophysiological response from two antennae of ALB could be estimated either at a minimum concentration (2.49 × 10⁸ at 0.01 ng/μL concentration of (Z)-3-Hexenol, for female) or at a minimum potentiometric response value (3.99 × 10⁴ at 0.01 mV potential value). Full article

According to our research, the flowers from Citrus grandis ‘Tomentosa’ contain rich biologically active essential oil components, but the chemical components and relative pharmacological properties have not been systematically studied. Therefore, the study aimed to identify the essential oil components by GC-MS/MS and explore the pharmacological activity and mechanism of these essential oil components by a network pharmacology approach. Finally, GC-MS/MS analysis identified 43 essential oil components, which corresponded to 739 potential targets. GO analysis results showed that 12, 18, and 12 entries were related to biological processes, cellular components, and molecular functions, respectively. A total of 120 pathways were obtained based on KEGG analysis, of which the most important was the adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway. The “active component–target–disease” network further demonstrated these essential oil components’ potential efficacy against pain, tumors, neuropsychiatric diseases, eye diseases, and respiratory diseases, which were highly related to PPARA, GABRA1, PTGS2, and SLC6A2. Experimental validation confirmed that β-caryophyllene, a major constituent, dose-dependently inhibited the proliferation of HT29 and MCF-7 cells (0–320 μM). This study provides a reliable basis for elucidating the pharmacological activity of the essential oil components and related mechanisms, which is beneficial to the comprehensive utilization and development of Citrus grandis ‘Tomentosa’. Full article

In this study, a series of (Z)- and (E)-2-substituted-3-ferrocene-acrylonitrile derivatives were synthesized, characterized, and evaluated in vitro for their anticancer and anti-migration properties. The compounds were synthesized via the Knoevenagel condensation of the appropriate benzyl cyanide or benzoyl acetonitrile with ferrocenecarboxaldehyde 1, producing isolated yields of 99 to 23%. The structures of the compounds were analyzed using IR, ¹H NMR, ¹³C{¹H} NMR, GC-MS, and UV/Vis spectroscopic methods. Single-crystal X-ray diffraction analysis of representative compounds 21, 27, and 29 demonstrated that the geometry of the double bond was that of the (Z)-isomer. For representative compound 33, the geometry of the double bond was that of the (E)-isomer. Additionally, the electrochemistry of the compounds was investigated using cyclic voltammetry. The cytotoxic and anti-migratory effects of these compounds were evaluated in the MCF-7 and MDA-MB-231 breast cancer cell lines, providing insight into the structure–activity relationships. Preliminary investigations of their anticancer activity revealed that several compounds exhibit moderate antiproliferative effects on cancer cell lines, with GI₅₀ values ranging from 23 to 44 μM for the MCF-7 cell line and from 9 to 41 μM for the MDA-MB-231 cell line. Moreover, compound (Z)-25 inhibited 13% of the migration activity of the metastatic MDA-MB-231 cell line. Full article

Background: Osteoporosis is a systemic disease characterized by a progressive decrease in bone density and deterioration of the tissue’s microarchitecture. This results in greater structural fragility and a higher risk of fractures. Osteopenia represents the beginning of the process of decreasing bone density and, if left untreated, can lead to osteoporosis. The objective of this study was to validate an experimental model for establishing cases of decreased bone density that allows for the creation of different levels of severity of mineral loss and changes in bone microstructure. Materials and Methods: Twenty female Wistar rats, 12 weeks old and with a body weight ranging from 300 to 400 g, were used in this study. The animals were randomly distributed into five groups (n = 5 per group): a control group (CG), where the animals were not ovariectomized (OVX), and four experimental groups, where the animals were OVX and euthanized at different times: 30 days (G30), 40 days (G40), 60 days (G60), and 80 days (G80). The animals in the experimental groups underwent bilateral ovariectomy to induce mineral loss. The femurs were collected after the periods established for each group and analyzed using microcomputed tomography (μCT) to determine bone density and count the number of trabeculae. Furthermore, the T-score was calculated for each group. Results: There were significant differences in bone density when comparing all groups, with GC > G30 > G40 > G60 > G80. For the number of trabeculae, GC presented more trabeculae than all other groups. More trabeculae were also observed in G30 when compared to G40, G60, and G80; however, there were no differences between G40, G60, and G80. Regarding the calculation of the T-score by group, osteopenia was observed in G30 (T-score: −2.42) and osteoporosis was observed in G40, G60, and G80 (T-scores: −4.38, −6.34, and −7.71, respectively). Conclusions: The results demonstrate that ovariectomy induces progressive changes in bone structure, with the onset of osteopenia 30 days after ovariectomy and osteoporosis after 40 days in this experimental model. These results may aid future investigations that seek to focus on the specific treatment of osteopenia and/or osteoporosis. Full article

Background and Objectives: The prognostic immune and nutritional index (PINI) was reported to be clinically relevant for colorectal cancer prognosis. Herein, the utility of PINI as a prognostic factor for the survival of patients with gastric cancer (GC) was investigated. Materials and Methods: We retrospectively analyzed 492 patients with stage I–III GC, predominantly of Asian descent, who underwent curative-intent gastrectomy. Multivariate Cox regression analysis identified independent predictors of overall survival (OS). Model performance was evaluated using the concordance index (C-index), integrated area under the curve (iAUC), time-dependent AUC, integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI). Results: The PINI score—calculated as [albumin (g/dL) × 0.9] − [absolute monocyte count (/μL) × 0.0007]—was found to be independently associated with OS (p < 0.001). Additional independent prognostic factors included age, body mass index, 5-factor modified frailty index, tumor–node–metastasis (TMN) stage, gastrectomy type, and anemia. The full model that included all significant covariates outperformed the baseline TNM model, showing significantly higher C-index and iAUC values (both p < 0.001). Compared with an intermediate model, which excluded PINI, the full model demonstrated a superior C-index and iAUC (both p = 0.004). Although the observed improvements in AUC, IDI, and cNRI at 3 years were not statistically significant, the full model achieved significant gains in all three metrics at 5 years, underscoring the added long-term prognostic value of the PINI. Conclusions: PINI is a significant independent predictor of survival in patients with GC who underwent curative-intent surgery. Its inclusion in prognostic models enhances the long-term predictive accuracy for survival, supporting its potential role in guiding personalized postoperative management. External validation in larger multi-ethnic prospective cohorts is essential to confirm its generalizability and to establish its role in routine clinical practice. Full article

This study aims to develop a simultaneous analytical method for detecting 19 pesticides, including 4,4′-DDD, in fishery products using gas chromatography with micro-electron capture detection (GC-μECD) and gas chromatography–tandem mass spectrometry (GC-MS/MS). A new analytical method was developed to measure pesticide residues in fishery products based on the modified Association of Official Analytical Chemists protocol combining quick, easy, cheap, effective, rugged, and safe (QuEChERS) and the Pesticide Analytical Manual for extraction and purification. Extraction was performed using acetonitrile containing 0.1% acetic acid, and purification was conducted with Florisil cartridges. The Florisil cartridges were more effective than QuEChERS in removing impurities and pigments during purification and also resulted in a reduced matrix effect. The validation followed Codex guidelines (CAC/GL 40). The limit of detection ranged from 2 to 3 ng/g, and the limit of quantification (LOQ) from 7 to 10 ng/g. Matrix-matched calibration curves exhibited linearity with coefficients of determination exceeding 0.99 for all target analytes. Accuracy was assessed based on recovery rates, while precision was evaluated using relative standard deviations (RSD) at three spiking levels (LOQ, 10×LOQ, and 50×LOQ). The recovery rates ranged from 62.6 to 119.1%, with RSDs of 0.4 to 19.5%, conforming to Codex guidelines. Full article

g-C₃N₄, a biocompatible material, has prominent applications in biology and is ideal for nano-enzyme studies. Though reported as a peroxidase mimic, its activity remains low. This group combined N,S-doped carbon quantum dots (NS-CQDs) with g-C₃N₄ (7NSC-g), verifying its peroxidase-like activity. Based on this, a ternary composite of Co₃O₄ in different forms and 7NSC-g was developed to enhance peroxidase activity, to design a g-C₃N₄-based composite enzyme. Characterizations determined the composition and morphology. Colorimetry evaluated peroxidase activity, where the simulated enzyme catalyzes blue product formation from the TMB substrate in the presence of H₂O₂. UV-Vis spectrophotometry measured absorbance changes to determine target concentrations. The results show Co₃O₄ doping improves catalytic activity, with larger specific surface area providing more activation sites. The highest activity of g-C₃N₄/NS-CQDs/Co₃O₄ was at 5% floral Co₃O₄, being efficient due to Co₃O₄’s electron-transfer acceleration and hydroxyl-radical mechanism. Under optimal conditions, the composite detected H₂O₂ (10.0–230.0 μM, detection limit of 0.031 μM) and glucose (10.0–650.0 μM, detection limit of 1.024 μM). Full article

The tomato russet mite (TRM), Aculops lycopersici, is a destructive pest of tomato crops worldwide. It poses a significant challenge to growers in both greenhouse and open-field conditions. Traditional chemical control methods are often ineffective, promote resistance, and have negative environmental impacts. This has prompted the search for alternative strategies, such as biological control and eco-friendly botanical pesticides. In this study, we evaluated the acaricidal effects of essential oils (EOs) extracted from three officinal plants, Origanum vulgare L., Salvia rosmarinus Spenn., and Salvia officinalis L., cultivated using precision aromatic crop (PAC) techniques. Their efficacy was evaluated against A. lycopersici under laboratory conditions. The chemical composition of the EOs was determined by solid-phase microextraction (SPME) coupled with gas chromatography–mass spectrometry (GC-MS). The dominant component of O. vulgare EO was carvacrol (83.42%), followed by ρ-cymene (3.06%), and γ-terpinene (2.93%). In S. rosmarinus, α-pinene (28.0%), 1,8-cineole (11.00%), and borneol (7.72%) were the major components. S. officinalis EO was characterized by high levels of 1,8-cineole (27.67%), camphor (21.91%), and crisantenone (12.87%). We tested multiple concentrations (320–5000 μL L−¹) and exposure times (1–4 days) to assess mite mortality. The results revealed both dose- and time-dependent toxic activity, with significant differences among EOs. O. vulgare EO was the most toxic, causing 90% mortality at 0.5% (w/v) concentration after 4 days. S. rosmatinus and S. officinalis EOs had more limited effects, with 46% and 42% mortality, respectively. Lethal concentration (LC₅₀) values were 2.23 mL L−¹ (95% CI: 1.74–3.05) for O. vulgare, 5.84 mL L−¹ (95% CI: 3.28–22.29) for S. rosmarinus, and 6.01 mL L−¹ (95% CI: 2.63–261.60) for S. officinalis. These results indicate that O. vulgare EO shows efficacy comparable to commercially available botanical pesticides. Our findings support the potential of O. vulgare EO as a viable alternative for the control of A. lycopersici, contributing to integrated pest management (IPM) strategies. Full article

Camellia ptilophylla Chang (C. ptilophylla), a unique low-caffeine tea species, is valued for its bioactive properties, especially antioxidant and anticancer activities, due to its distinct phytochemical profile. However, its precise constituents and mechanisms remain poorly understood. This study employs an integrated approach combining chromatographic separation, bioinformatic analysis, and cellular assays to systematically investigate the antioxidant and anticancer properties of C. ptilophylla and elucidate its underlying molecular mechanisms. Quantitative analysis revealed that in addition to trans-catechins, the unique polyphenolic compounds, gallocatechin-3,5-di-O-gallate (GC-3,5-diGA) and 1,2,4,6-tetra-O-galloyl-β-D-glucopyranose (1,2,4,6-GA-glc), constituted significant proportions of C. ptilophylla extracts, with concentrations of 10.25 ± 0.29% and 6.60 ± 0.14%, respectively. Monomeric activity assessment demonstrated that both GC-3,5-diGA and 1,2,4,6-GA-glc exhibited pronounced antiproliferative effects against three cancer cell lines including the Lymph Node Carcinoma of the Prostate cell, human colon cancer cell, and human breast cancer cell. Notably, these compounds demonstrated potent antioxidant capacity, with 62.5 μM of GC-3,5-diGA and 15.63 μM of 1,2,4,6-GA-glc protecting against tBHP-induced oxidative stress in NIH3T3 cells comparable to 125 μM of epigallocatechin gallate and gallocatechin gallate in half-maximal inhibitory concentration. Mechanistic studies revealed that these polyphenols modulated antioxidant defenses and reactive oxygen species homeostasis via targets like fibroblast growth factor 2, telomerase reverse transcriptase, matrix metalloproteinase 9, and ATP-binding cassette subfamily G member 2, inducing oxidative stress and mitochondrial apoptosis to inhibit carcinogenesis. These findings enhance our understanding of the bioactive components responsible for the anticancer and antioxidant properties of C. ptilophylla and provide a scientific basis for the development of this dual-purpose plant for food and medicinal applications. Full article

Bisphenol A (BPA) is a common synthetic chemical compound classified as an endocrine disruptor. It affects multiple physiological systems in the body, including the female reproductive system, particularly granulosa cells (GCs) in the ovaries, where steroidogenesis occurs. This study investigated the impact of various BPA concentrations (environmentally relevant concentrations of 0.001 µM and 0.1 µM and toxicological concentration of 100 µM) and exposure times (24 and 72 h) on cell viability and counts and in vitro production of estradiol and progesterone in human GCs collected from waste follicular fluid of IVF patients. Gene expression analysis of 182 genes associated with steroidogenesis and apoptosis was performed in GCs using PCR arrays, followed by protein expression analysis by Western blot. Our results demonstrate that after longer BPA exposure (72 h), a higher concentration of BPA (100 µM) negatively affects the cellular viability and counts and significantly alters steroid hormone biosynthesis in vitro, leading to reduced concentrations of estradiol and progesterone in the culture medium. We found that all BPA concentrations altered the expression of different steroidogenesis- and apoptosis-related genes in GCs. At 0.001 μM, BPA exposure decreased the expression of TRIM25, UGT2B15, CASP3, and RPS6KA3 genes and increased the expression of NR6A1 and PPID genes. At 0.1 μM, BPA increased the expression of AR, HSD3B1, BID, IKBKG, and PPID genes while reducing the expression of TRIM25 and CASP3 genes. At the highest concentration of 100 μM, BPA upregulated the expression of AR, GPER30, BID, IKBKG, and PPID genes and downregulated the expression of FOXO1 and UGT2B15 genes. These results highlight BPA’s concentration-specific effects on steroidogenesis and apoptosis and show its potential to compromise GC function, with possible negative implications for female fertility and ovarian health, even at environmentally relevant concentrations. Full article

This study focuses on investigating the stability of modern and contemporary paints based on manganese violet pigment PV16 (NH₄MnP₂O₇) when exposed to atmospheric pollutants, specifically sulfur dioxide (SO₂) in the presence of high relative humidity. In particular, this study aims to investigate the role of PV16 in increasing the degradation processes of various modern binders. Therefore, the objectives of this research can be divided into (i) evaluating the chemical modifications involving PV16, (ii) investigating the degradation processes that occur in different organic matrices (i.e., drying oil, alkyd resin, and acrylic and styrene–acrylic emulsions), and (iii) comparing the chemical stability of model and commercial paints. The paints were analyzed by 3D Optical Microscopy, Attenuated total Reflection–Fourier-Transform Infrared spectroscopy (ATR-FTIR) and μ-Raman Spectroscopy, Scanning Electron Microscope coupled with Energy Dispersive X-Ray spectroscopy (SEM-EDX), X-Ray Powder Diffraction (XRPD), Fiber Optic Reflectance Spectroscopy (FORS), Pyrolysis–Gas Chromatography–Mass Spectrometry (Py-GC/MS), and Thermally assisted Hydrolysis and Methylation (THM) of Py-GC/MS (THM-Py-GC/MS). The results show that when exposed to high relative humidity and SO₂, PV16 presents a colorimetric change from violet to grey; several compounds crystallize on the surface; and, depending on the binder, various degradation reactions occur. This study highlights the susceptibility of manganese violet pigment PV16 under certain environmental conditions, which may be considered to define adequate conservation strategies for works of art containing this specific pigment. Additionally, the results obtained within this investigation point out the need to expand the chemical knowledge of this material for engineering, sensing, and industrial applications. Full article

Antioxidants from natural sources are essential for the development of new therapeutics to improve human health. The objects of study are the aerial flowering parts of Potentilla argentea, a plant species known in traditional medicine for the astringent, hemostatic, wound-healing, and anti-inflammatory effects of its rhizomes. A Potentillae argenteae herba ethanol dry tincture was chromatographically analyzed (GC/MS, HPLC) and its antioxidant (ABTS, DPPH, CUPRAC, FRAP assays) and DNA nicking protection potentials were evaluated. The eighteen volatiles were identified by GC/MS, where the predominant components were n-nonacosane (39.38 mg/g dt), squalene (28.88 mg/g dt), n-tricosane (18.36 mg/g dt), ethyl oleate (15.24 mg/g dt), and n-pentacosane (10.60 mg/g dt). A high content of total polyphenols was obtained (440.78 mg GAE/g dt), and HPLC analysis identified two flavonoids and three phenolic acids, of which rosmarinic acid and rutin were above 10 mg/g dt. The tincture exhibited strong antioxidant activity by all four methods, especially CUPRAC assay (8617.54 μM TE/g). DNA protective activity against oxidative damage and microscopic identification of P. argenteae herba powder were established for the first time. Therefore, the tincture could be incorporated into phytopreparations for the treatment of human diseases caused by reactive oxygen species. Full article

The study of the genetic diversity and adaptation mechanisms of the Kazakh apricot (Prunus armeniaca L.) is essential for breeding programs and the conservation of plant genetic resources in arid environments. Despite this species’ ecological and agricultural significance, its chloroplast genome remains poorly studied due to its complex repetitive structure and secondary metabolites that hinder high-molecular-weight DNA (HMW-DNA) extraction and long-read sequencing. To address this gap, our study aims to develop and optimise sequencing protocols for P. armeniaca under arid conditions using Oxford Nanopore’s MinION technology. We successfully extracted HMW-DNA with 50–100 ng/μL concentrations and purity (A260/A280) between 1.8 and 2.0, ensuring high sequencing quality. A total of 10 GB of sequencing data was generated, comprising 155,046 reads, of which 74,733 (48.2%) had a Q-score ≥ 8. The average read length was 1679 bp, with a maximum of 31,144 bp. Chloroplast genome assembly resulted in 33,000 contigs with a total length of 1.1 Gb and a BUSCO completeness score of 97.3%. Functional annotation revealed key genes (nalC, AcrE, and mecC-type BlaZ) associated with stress tolerance and a substantial proportion (≈40%) of hypothetical proteins requiring further investigation. GC content analysis (40.25%) and GC skew data suggest the presence of specific regulatory elements linked to environmental adaptation. This study demonstrates the feasibility of using third-generation sequencing technologies to analyse complex plant genomes and highlights the genetic resilience of P. armeniaca to extreme conditions. The findings provide a foundation for breeding programs to improve drought tolerance and conservation strategies to protect Kazakhstan’s unique arid ecosystems. Full article

This investigation evaluates the comparative efficacy of Cinnamomum burmannii leaf essential oil (YXYO) and its main active ingredients as a novel preservative to protect stored food commodities from fungal infestations, aflatoxin B₁ (AFB₁) contamination caused by Aspergillus flavus. Morphological observations utilizing SEM and TEM revealed significant alterations in treated samples, alongside a decrease in ergosterol content and a dose-dependent disruption of the antioxidant system and energy system. Transcriptomic analysis suggested that differentially expressed genes were predominantly associated with spore growth, the cell wall, the cell membrane, oxidative stress, energy metabolism, and aflatoxin biosynthesis. Solid-phase microextraction–gas chromatography–mass spectrometry (SPME-GC-MS) identified ten active ingredients in YXYO, including borneol, α-terpineol, terpinen-4-ol, etc. Moreover, an effective inhibition of A. flavus infection in peanuts was observed with the application of 30 μL/disc of YXYO and a blend of its active compounds. Full article