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Long non-coding RNAs (lncRNAs) play crucial roles in a variety of biological processes, including stress response. However, the number, characteristics and stress-related expression of lncRNAs in turbot are still largely unknown. In this study, a total of 12,999 lncRNAs were identified at the genome-wide level of turbot for the first time using 24 RNA-seq datasets. Sequence characteristic analyses of transcripts showed that lncRNA transcripts were shorter in average length, lower in average GC content and in average expression level as compared to the coding genes. Expression pattern analyses of lncRNAs in 12 distinct tissues showed that lncRNAs, especially lincRNA, exhibited stronger tissue-specific expression than coding genes. Moreover, 612, 1351, 1060, 875, 420 and 1689 differentially expressed (DE) lncRNAs under Vibrio anguillarum, Enteromyxum scophthalmi, and Megalocytivirus infection and heat, oxygen, and salinity stress conditions were identified, respectively. Among them, 151 and 62 lncRNAs showed differential expression under various abiotic and biotic stresses, respectively, and 11 lncRNAs differentially expressed under both abiotic and biotic stresses were selected as comprehensive stress-responsive lncRNA candidates. Furthermore, expression pattern analysis and qPCR validation both verified the comprehensive stress-responsive functions of these 11 lncRNAs. In addition, 497 significantly co-expressed target genes (correlation coefficient (R) > 0.7 and q-value < 0.05) for these 11 comprehensive stress-responsive lncRNA candidates were identified. Finally, GO and KEGG enrichment analyses indicated that these target genes were enriched mainly in molecular function, such as cytokine activity and active transmembrane transporter activity, in biological processes, such as response to stimulus and immune response, and in pathways, such as protein families: signaling and cellular processes, transporters and metabolism. These findings not only provide valuable reference resources for further research on the molecular basis and function of lncRNAs in turbot but also help to accelerate the progress of molecularly selective breeding of stress-resistant turbot strains or varieties. [ABSTRACT FROM AUTHOR]

DNA repair involves various intricate pathways that work together to maintain genome integrity. XPF (ERCC4) is a structural endonuclease that forms a heterodimer with ERCC1 that is critical in both single-strand break repair (SSBR) and double-strand break repair (DSBR). Although the mechanistic function of ERCC1/XPF has been established in nucleotide excision repair (NER), its role in long-patch base excision repair (BER) has recently been discovered through the 5′-Gap pathway. This study briefly explores the roles of XPF in different pathways to emphasize the importance of XPF in DNA repair. XPF deficiency manifests in various diseases, including cancer, neurodegeneration, and aging-related disorders; it is also associated with conditions such as Xeroderma pigmentosum and fertility issues. By examining the molecular mechanisms and pathological consequences linked to XPF dysfunction, this study aims to elucidate the crucial role of XPF in genomic stability as a repair protein in BER and provide perspectives regarding its potential as a therapeutic target in related diseases. [ABSTRACT FROM AUTHOR]

Biomimetic hydrogels have garnered increased interest due to their considerable potential for use in various fields, such as tissue engineering, 3D cell cultivation, and drug delivery. The primary challenge for applying hydrogels in tissue engineering is accurately evaluating their mechanical characteristics. In this context, we propose a method using scanning ion conductance microscopy (SICM) to determine the rigidity of living human breast cancer cells MCF-7 cells grown on a soft, self-assembled Fmoc-FF peptide hydrogel. Moreover, it is demonstrated that the map of Young's modulus distribution obtained by the SICM method allows for determining the core location. The Young's modules for MCF-7 cells decrease with the substrate stiffening, with values of 1050 Pa, 835 Pa, and 600 Pa measured on a Petri dish, Fmoc-FF hydrogel, and Fmoc-FF/chitosan hydrogel, respectively. A comparative analysis of the SICM results and the data obtained by atomic force microscopy was in good agreement, allowing for the use of a composite cell–substrate model (CoCS) to evaluate the 'soft substrate effect'. Using the CoCS model allowed us to conclude that the MCF-7 softening was due to the cells' mechanical properties variations due to cytoskeletal changes. This research provides immediate insights into changes in cell mechanical properties resulting from different soft scaffold substrates. [ABSTRACT FROM AUTHOR]

This study describes two siblings from consanguineous parents who exhibit intellectual disability, microcephaly, photosensitivity, bilateral sensorineural hearing loss, numerous freckles, and other clinical features that suggest a potential disruption of the nucleotide excision repair (NER) pathway. Whole exome sequencing (WES) identified a novel homozygous missense variant in the ERCC4 gene, which was predicted to be pathogenic. However, a subsequent peculiar audiometric finding prompted further investigation, revealing a homozygous deletion in the OTOA gene linked to neurosensorial hearing loss. Both variants were located within a run of homozygosity (ROH) on chromosome 16p13.12-p12.2, implicating a complex genetic basis for the observed phenotype. While this study reports a potentially novel ERCC4 variant, it underscores the importance of comprehensive analysis and deep phenotyping in WES data to improve diagnostic accuracy. Our findings advocate for an expanded approach in WES analysis, ensuring more precise diagnoses and improved genetic counseling, particularly when specialized tests for structural variant analysis are unavailable. [ABSTRACT FROM AUTHOR]

The progressive development of resistance in Neisseria gonorrhoeae to almost all available antibiotics has made it crucial to develop novel approaches to tackling multi-drug resistance (MDR). One of the primary causes of antibiotic resistance is the over-expression of the MtrCDE efflux pump protein, making this protein a vital target for fighting against antimicrobial resistance (AMR) in N. gonorrhoeae. This study was aimed at evaluating the potential MtrCDE efflux pump inhibitors (EPIs) and their stability in treating gonorrhoea infection. This is significant because finding novel EPIs would allow for the longer maintenance of antibiotics at therapeutic levels, thereby prolonging the susceptibility of currently available antibiotics. A virtual screening of the selected Helichrysum populifolium compounds (4,5-dicaffeoylquinic acid, apigeninin-7-glucoside, and carvacrol) was conducted to evaluate their potential EPI activity. An integrated computational framework consisting of molecular docking (MD), molecular mechanics generalized born, and surface area solvation (MMGBSA) analysis, molecular dynamics simulations (MDS), and absorption, distribution, metabolism, and excretion (ADME) properties calculations were conducted. Of the tested compounds, 4,5-dicaffeoylquinic acid revealed the highest molecular docking binding energies (−8.8 kcal/mol), equivalent MMGBSA binding free energy (−54.82 kcal/mol), indicative of consistent binding affinity with the MtrD protein, reduced deviations and flexibility (root mean square deviation (RMSD) of 5.65 Å) and, given by root mean square fluctuation (RMSF) of 1.877 Å. Carvacrol revealed a docking score of −6.0 kcal/mol and a MMGBSA computed BFE of −16.69 kcal/mol, demonstrating the lowest binding affinity to the MtrD efflux pump compared to the remaining test compounds. However, the average RMSD (4.45 Å) and RMSF (1.638 Å) of carvacrol-bound MtrD protein showed no significant difference from the unbound MtrD protein, except for the reference compounds, implying consistent MtrD conformation throughout simulations and indicates a desirable feature during drug design. Additionally, carvacrol obeyed the Lipinski rule of five which confirmed the compound's drug-likeness properties making it the most promising EPI candidate based on its combined attributes of a reasonable binding affinity, sustained stability during MDS, its obedience to the Lipinski rule of five and compliance with drug-likeness criteria. An in vitro validation of the potential EPI activities of H. populifolium compounds confirmed that 4,5-dicaffeoylquinic acid reduced the expulsion of the bis-benzimide dye by MtrCDE pump, while carvacrol showed low accumulation compared to other compounds. While 4,5-dicaffeoylquinic acid demonstrated the highest binding affinity in computational analysis and an EPI activity in vitro, it showed lower stability compared to the other compounds, as indicated in MDS. This leaves carvacrol, as a better EPI candidate for the management of gonorrhoea infection. [ABSTRACT FROM AUTHOR]

Inspired by the reported crystal structure of compound 1, we aimed to synthesize and determine the structure of compound 2, where two imidazolium (H2im+) ions serve as diamagnetic countercations. Here, we report the thermal stabilities, FT–IR, visible, and RSE spectra, as well as the magnetic properties of both compounds. In these structures, µ-EDTA acts as a pentadentate chelator for both terminal Cu centers within the centrosymmetric linear trinuclear anion. The Cu(µ-EDTA) chelates bind to the central Cu(Him)4 unit in subtly different ways: in compound 1, µ-EDTA has a free acetate arm and binds the central Cu(II) center through a syn,anti-carboxylate group. In contrast, in compound 2, the non-chelating acetate arm serves as a monodentate O-donor to the central Cu(II) atom, increasing the Cu(terminal)···Cu(central) distance from 6.08 Å in 1 to 6.80 Å in 2. Additionally, pairs of H2im+ ions in compound 2 display antiparallel π-stacking interactions. We conclude that the H2im+ counterions in compound 2 enable the magnetic isolation of the nearly identical trinuclear anion present in both compounds. DFT calculations further support the role of different interactions in stabilizing each crystal structure. In compound 2, dominant contributions from N–H···O hydrogen bonds and π-stacking interactions are accompanied by other, less conventional interactions, such as multiple C–H···O contacts and an O···CO(π-hole) interaction within the trinuclear anion. [ABSTRACT FROM AUTHOR]

The RNA-binding S1 domain is a β-barrel with a highly conserved RNA-binding site on its surface. This domain is an important part of the structures of different bacterial, archaeal, and eukaryotic proteins. A distinctive feature of the S1 domain is multiple presences (structural repeats) in proteins and protein complexes. Here, we have analyzed all available protein sequences in the UniProt database to obtain data on the distribution of bacterial, eukaryotic and archaeal proteins containing the S1 domain. Mainly, the S1 domain is found in bacterial proteins with the number of domains varying from one to eight. Eukaryotic proteins contain from one to fifteen S1 domains, while in archaeal proteins, only one S1 domain is identified. Analysis of eukaryotic proteins containing S1 domains revealed a group of chloroplast S1 ribosomal proteins (ChRpS1) with characteristic properties of bacterial S1 ribosomal proteins (RpS1) from the Cyanobacteria. Also, in a separate group, chloroplast and mitochondrial elongation factor Ts containing two S1 structural domains were assigned. For mitochondrial elongation factor Ts, the features of S1 in comparison with the RpS1 from Cyanobacteria phylum and the Alphaproteobacteria class were revealed. The data obtained allow us to consider the S1 domain as one of the evolutionary markers of the symbiogenesis of bacterial and eukaryotic organisms. [ABSTRACT FROM AUTHOR]

Stress granules (SGs) are membrane-less aggregates that form in response to various cellular stimuli through a process called liquid–liquid phase separation (LLPS). Stimuli such as heat shock, osmotic stress, oxidative stress, and infections can induce the formation of SGs, which play crucial roles in regulating gene expression to help cells adapt to stress conditions. Various mRNAs and proteins are aggregated into SGs, particularly those associated with the protein translation machinery, which are frequently found in SGs. When induced by infections, SGs modulate immune cell activity, supporting the cellular response against infection. The roles of SGs differ in viral versus microbial infections, and depending on the type of immune cell involved, SGs function differently in response to infection. In this review, we summarize our current understanding of the implication of SGs in immunity and cellular organelles in the context of infectious diseases. Importantly, we explore insights into the regulatory functions of SGs in the context of host cells under infection. [ABSTRACT FROM AUTHOR]

Sophora japonica is an important native tree species in northern China, with high ornamental, medicinal, and ecological value. In order to elucidate the genetic resources of ancient S. japonica, 16 simple sequence repeat (SSR) markers were used to evaluate its genetic diversity and population structure and build a core collection of 416 germplasms from the Shandong, Shanxi, and Hebei provinces. A total of 160 alleles were detected, the mean major allele frequency (MAF)was 0.39, and the mean effective number of alleles (Ne) was 4.08. Shannon's information index (I), the observed heterozygosity (Ho), the expected heterozygosity (He), and the polymorphism information content (PIC) were 1.58, 0.64, 0.74, and 0.70, respectively, indicating relatively high genetic diversity in ancient S. japonica germplasms. Low genetic differentiation coefficient (Fst = 0.04) and frequent gene flow (Nm = 9.74) were found in the tested S. japonica populations, and an analysis of molecular variance (AMOVA) indicated that the genetic variation mainly came from within individuals (84%). A genetic structure and cluster analysis indicated that 416 ancient S. japonica germplasms could be divided into five subgroups, and there were obvious genetic exchanges among different subgroups. A core collection consisting of 104 (25% of the original collection) germplasms was constructed using the R language package Genetic Subsetter version 0.8 based on the stepwise regression method. The retention rates of the number of alleles (Na), Ne, I, He, and PIC were 87.50%, 106.24%, 103.02%, 102.50%, and 102.74%, respectively. The t-test analysis suggested that there were no significant differences between the core collection and the original collection. The principal coordinate analysis (PCoA) showed that the core collection was uniformly distributed within the initial collection and was able to fully represent the genetic diversity of the original collection. These results provide a scientific basis for the conservation and utilization of ancient S. japonica germplasms. [ABSTRACT FROM AUTHOR]

This study evaluated the salinity tolerance of five populations of Salvia subg. Perovskia (S. abrotanoides and S. yadngii). The aims of the study were to assess essential oil components, as well as growth and physiological parameters of two Salvia species in response to salt stress. Four different levels of salinity (0, 60, 90, and 120 mM NaCl) were applied. The effects of various concentrations of NaCl on essential oil content, composition, growth, water relation, proline, lipid peroxidation (MDA), hydrogen peroxide content, and antioxidant enzyme activity, as well as Na and K contents in leaves and the roots were evaluated. The results revealed that root dry weight loss was higher than that of shoots, indicating root vulnerability due to direct exposure to the salt stress. The lowest and highest oil content was obtained in PATKH (0.6%) at 60 mM and PABAD (0.6%) in 90 mM to 2.16% in PABSM population under 120 mM NaCl. Based on GC-MS analysis, 1,8-cineol (11.64 to 22.02%), camphor (2.67 to 27.14%), bornyl acetate (2.12 to 11.07%), borneol (2.38 to 24.37%), β-caryophyllene (3.24 to 7.58%), α-humulene (2.97 to 7.92%), and δ-3-carene (5.31 to 26.65%) were the most abundant compounds. Based on the principal component analysis (PCA), the most salinity-tolerant populations belonged to P. abrotanoides species. These populations are characterized by high root stress tolerance index (STI), root elements, and relative water content (RWC) with elevated levels of salinity stress. Finally, the findings might be useful in unraveling the salinity tolerance mechanisms for integrating stress tolerance with medicinal qualities in future studies. [ABSTRACT FROM AUTHOR]

Due to population growth and global technological development, energy consumption has increased exponentially. The global energy crisis opens up many hotly debated topics regarding energy generation and consumption. Not only is energy production in short supply due to limited energy resources but efficient and sustainable storage has become a very important goal. Currently, there are energy storage devices such as batteries, capacitors, and super-capacitors. Supercapacitors or electrochemical capacitors can be very advantageous replacements for batteries and capacitors because they can achieve higher power density and energy density characteristics. The evolution and progress of society demand the use of innovative and composite nanostructured metal oxide materials, which fulfill the requirements of high-performance technologies. This review mainly addresses the synthesis techniques and properties of 2D and 3D metal oxide nanostructured materials, especially based on Ti, Fe, Ga, and Sn ions, electrochemical methods used for the characterization and application of 2D, and 3D nanostructured metal oxide structures in electrochemical storage systems of energy. [ABSTRACT FROM AUTHOR]

Photosystem I in most organisms contains long-wavelength or "Red" chlorophylls (Chls) absorbing light beyond 700 nm. At cryogenic temperatures, the Red Chls become quasi-traps for excitations as uphill energy transfer is blocked. One pathway for de-excitation of the Red Chls is via transfer to the oxidized RC (P700+), which has broad absorption in the near-infrared region. This study investigates the excitation dynamics of Red Chls in Photosystem I from the cyanobacterium Thermostichus vulcanus at cryogenic temperatures (77 K) and examines the role of the oxidized RC in modulating their fluorescence kinetics. Using time-resolved fluorescence spectroscopy, the kinetics of Red Chls were recorded for samples with open (neutral P700) and closed (P700+) RCs. We found that emission lifetimes in the range of 710–720 nm remained unaffected by the RC state, while more red-shifted emissions (>730 nm) decayed significantly faster when the RC was closed. A kinetic model describing the quenching by the oxidized RC was constructed based on simultaneous fitting to the recorded fluorescence emission in Photosystem I with open and closed RCs. The analysis resolved multiple Red Chl forms and variable quenching efficiencies correlated with their spectral properties. Only the most red-shifted Chls, with emission beyond 730 nm, are efficiently quenched by P700+, with rate constants of up to 6 ns−1. The modeling results support the notion that structural and energetic disorder in Photosystem I can have a comparable or larger effect on the excitation dynamics than the geometric arrangement of Chls. [ABSTRACT FROM AUTHOR]

CD155, also known as the poliovirus receptor (PVR), is a crucial molecule in the development and progression of cancer, as its overexpression favors immune evasion and resistance to immunotherapy. However, little is known about the mechanisms that regulate its overexpression. Proinflammatory factors produced by various cellular components of the tumor microenvironment (TME) have been associated with CD155 expression. We analyzed the effect of interleukin (IL)-6 on CD155 expression in lung adenocarcinoma. We found a positive relationship between mRNA and protein levels. This correlation was also observed in bioinformatics analysis and in biopsies and serum from patients with lung adenocarcinoma. Interestingly, lung adenocarcinoma cell lines expressing suppressor of cytokine signaling 1 (SOCS1) did not show increased CD155 levels upon IL-6 stimulation, and SOCS1 silencing reverted this effect. IL-6 and SOCS1 are critical regulators of CD155 expression in lung adenocarcinoma. Further basic and clinical studies are needed to define the role of these molecules during tumor development and to improve their clinical impact as biomarkers and targets for predicting the efficacy of immunotherapies. This study deepens the understanding of the intricate regulation of the immune checkpoints mediated by soluble factors and allows us to devise new ways to combine conventional treatments with the most innovative anticancer options. [ABSTRACT FROM AUTHOR]

The structure–tissue exposure/selectivity relationship (STR) aids in lead optimization to improve drug candidate selection and balance clinical dose, efficacy, and toxicity. In this work, butyrocholinesterase (BuChE)-targeted cannabidiol (CBD) carbamates were used to study the STR in correlation with observed efficacy/toxicity. CBD carbamates with similar structures and same molecular target showed similar/different pharmacokinetics. L2 and L4 had almost same plasma exposure, which was not correlated with their exposure in the brain, while tissue exposure/selectivity was correlated with efficacy/safety. Structural modifications of CBD carbamates not only changed drug plasma exposure, but also altered drug tissue exposure/selectivity. The secondary amine of carbamate can be metabolized into CBD, while the tertiary amine is more stable. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters can be used to predict STR. Therefore, STR can alter drug tissue exposure/selectivity in normal tissues, impacting efficacy/toxicity. The drug optimization process should balance the structure–activity relationship (SAR) and STR of drug candidates for improving clinical trials. [ABSTRACT FROM AUTHOR]

The prevalence of small multi-target drugs containing a fluorinated aromatic moiety among approved drugs in the market is due to the unique properties of this halogen atom. With the aim to develop potent antidiabetic agents, a series of phenylsulfonic esters based on the conjugation of the 5-substituted 2-hydroxy-3-nitroacetophenones 1a–d with phenylsulfonyl chloride derivatives substituted with a fluorine atom or fluorine-containing (-CF3 or -OCF3) group were prepared. Their structures were characterized using a combination of spectroscopic techniques complemented with a single-crystal X-ray diffraction (XRD) analysis on a representative example. The compounds were, in turn, assayed for inhibitory effect against α-glucosidase, α-amylase, protein tyrosine phosphatase 1 B (PTP1B) and the vascular endothelial growth factor receptor-2 (VEGFR-2) all of which are associated with the pathogenesis and progression of type 2 diabetes mellitus (T2DM). The antigrowth effect of selected compounds was evaluated on the human breast (MCF-7) and lung (A549) cancer cell lines. The compounds were also evaluated for cytotoxicity against the African Green Monkey kidney (Vero) cell line. The results of an in vitro enzymatic study were augmented by molecular docking (in silico) analysis. Their ADME (absorption, distribution, metabolism and excretion) properties have been evaluated on the most active compounds against α-glucosidase and/or α-amylase to predict their drug likeness. [ABSTRACT FROM AUTHOR]

Heterogeneous Mg-Fe oxide/biochar (MgFeO@BC) nanocomposites were synthesized by a co-precipitation method and used as biochar-based catalysts to activate peroxymonosulfate (PMS) for sulfamethoxazole (SMX) removal. The optimal conditions for SMX degradation were examined as follows: pH 7.0, MgFeO@BC of 0.4 g/L, PMS concentration of 0.6 mM and SMX concentration of 10.0 mg/L at 25 ℃. In the MgFeO@BC/PMS system, the removal efficiency of SMX was 99.0% in water within 40 min under optimal conditions. In the MgFeO@BC/PMS system, the removal efficiencies of tetracycline (TC), cephalexin (CEX), ciprofloxacin (CIP), 4-chloro-3-methyl phenol (CMP) and SMX within 40 min are 95.3%, 98.4%, 98.2%, 97.5% and 99.0%, respectively. The radical quenching experiments and electron spin resonance (ESR) analysis suggested that both non-radical pathway and radical pathway advanced SMX degradation. SMX was oxidized by sulfate radicals (SO4•−), hydroxyl radicals (•OH) and singlet oxygen (1O2), and SO4•− acted as the main active species. MgFeO@BC exhibits a higher current density, and therefore, a higher electron migration rate and redox capacity. Due to the large number of available binding sites on the surface of MgFeO@BC and the low amount of ion leaching during the catalytic reaction, the system has good anti-interference ability and stability. Finally, the intermediates of SMX were detected. [ABSTRACT FROM AUTHOR]

A novel hybrid compound—2-(4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-imine (5) was synthesized and converted into di-substituted sulfonamide derivatives 6a–o and phthalazine ring opening products—hydrazonomethylbenzonitriles 7a–m. The newly prepared compounds were characterized using elemental analyses, IR and NMR spectroscopy, as well as mass spectrometry. Single crystal X-ray diffraction data were collected for the representative compounds 5, 6c, 6e, 7g, and 7k. The antiproliferative activity of compound 5, sulfonyl derivatives 6a–o and benzonitriles 7a–m was evaluated on approximately sixty cell lines within nine tumor-type subpanels, including leukemia, lung, colon, CNS, melanoma, ovarian, renal, prostate, and breast. None of the tested compounds showed any activity against the cancer cell lines used. The antioxidant properties of all compounds were assessed using the DPPH, ABTS, and FRAP radical scavenging methods, as well as the β-carotene bleaching test. Antiradical tests revealed that among the investigated compounds, a moderate ABTS antiradical effect was observed for sulfonamide 6j (IC50 = 52.77 µg/mL). Benzonitrile 7i bearing two chlorine atoms on a phenyl ring system showed activity in a β-carotene bleaching test (IC50 = 86.21 µg/mL). Finally, the interaction AGE/RAGE in the presence of the selected phthalazinimines 6a, 6b, 6g, 6m, and hydrazonomethylbenzonitriles 7a, 7c–g, and 7i–k was determined by ELISA assay. A moderate inhibitory potency toward RAGE was found for hydrazonomethylbenzonitriles—7d with an electron-donating methoxy group (R = 3-CH3O-C6H4) and 7f, 7k with an electron-withdrawing substituent (7f, R = 2-Cl-C6H4; 7k, R = 4-NO2-C6H4). [ABSTRACT FROM AUTHOR]

There are hereditary mutations that predispose individuals to cancer development, such as pathogenic variants in the germ line of the tumor protein 53 (TP53) suppressor gene. This leads to a rare condition known as Li–Fraumeni syndrome (LFS), characterized by a high risk of developing multiple cancers throughout life by the precancerous niche that promotes the tumor microenvironment. LFS presents a significant challenge due to its limited therapeutic and chemoprophylactic options. Recently, protocols involving metformin as a prophylactic medication have been developed to target precancerous niches. However, this approach is still in the clinical phase, and no established therapeutic regimen is available. Therefore, new alternatives are needed to impact this disease effectively. Novel studies suggest that Sechium extract, rich in polyphenols, exhibits chemoprophylactic, antineoplastic, anti-inflammatory, and antioxidant activities, all involved in the tumor microenvironment of LFS. However, the specific role of Sechium extract in preventing recurrent neoplastic development in LFS remains unclear. We conducted this research through a case report of an LFS-diagnosed patient who has experienced multiple malignancies and cutaneous neoformations. This patient received a chemoprophylactic supplementation based on Sechium H387 07 extract over 11 years without reporting new primary malignancy events or recurrences, as evidenced by laboratory and positron emission tomography/computed tomography (PET/CT) studies. An extensive literature review on the disease, precancerous niche, tumor microenvironment, and potential mechanisms of Sechium H387 07 extract components was conducted to explain cancer absence in LFS. This review promotes the research and use of polyphenols as powerful chemoprophylactic agents to prevent and treat proliferative diseases like LFS. [ABSTRACT FROM AUTHOR]

The identification of natural products (NPs) has played a pivotal role in drug discovery and shaped the evolution of synthetic compounds (SCs). However, the extent to which NPs have historically influenced the structural characteristics of SCs remains unclear. In this study, we conducted a comprehensive, time-dependent chemoinformatic analysis to investigate the impact of NPs on the structural evolution of SCs. The physicochemical properties, molecular fragments, biological relevance, and chemical space of the molecules from the Dictionary of Natural Products were compared in a time series fashion with a synthetic compound collection sourced from 12 databases. Our findings reveal that NPs have become larger, more complex, and more hydrophobic over time, exhibiting increased structural diversity and uniqueness. Conversely, SCs exhibit a continuous shift in physicochemical properties, yet these changes are constrained within a defined range governed by drug-like constraints. SCs possess a broader range of synthetic pathways and structural diversity, albeit with a decline in biological relevance. The chemical space of NPs has become less concentrated compared to that of SCs. In conclusion, our study suggests that the structural evolution of SCs is influenced by NPs to some extent; however, SCs have not fully evolved in the direction of NPs. [ABSTRACT FROM AUTHOR]

Abiotic stress affects the growth and development of maize (Zea mays). The regulator of chromosome condensation 1 (RCC1)-containing proteins (RCPs) plays crucial roles in plant growth and development and response to abiotic stresses. However, a comprehensive analysis of the maize RCP family has not been reported in detail. This study presents a systematic bioinformatics analysis of the ZmRCP family, identifying a total of 30 members distributed across nine chromosomes. The physicochemical properties and cis-acting elements in the promoters of ZmRCP members are predicted. The results of subcellular localization showed that ZmRCP3 and ZmRCP10 are targeted to mitochondria and ZmRCP2 is localized in the nucleus. A heatmap of expression levels among family members under abiotic stress conditions revealed varying degrees of induced expression, and the expression levels of 10 ZmRCP members were quantified using RT-qPCR under abiotic stress and plant hormone treatments. The results showed that ZmRCP members exhibit induced or inhibited responses to these abiotic stresses and plant hormones. These results contribute to a better understanding of the evolutionary history and potential role of the ZmRCP family in mediating responses to abiotic stress in maize. [ABSTRACT FROM AUTHOR]

This study investigates the degradation of six different types of absorbable surgical threads commonly used in clinical practice, focusing on their response to exposure to physiological fluids. The threads were subjected to hydrolytic and enzymatic degradation in physiological saline, bile, and pancreatic juice. Our findings demonstrate that bile and pancreatic juice, particularly when contaminated with bacterial strains such as Escherichia coli, Klebsiella spp., and Enterococcus faecalis, significantly accelerate the degradation process. Using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and tensile strength testing, we observed distinct differences in the chemical structure and mechanical integrity of the sutures. Principal component analysis (PCA) of the FTIR spectra revealed that PDS threads exhibited the highest resistance to degradation, maintaining their mechanical properties for a longer duration compared with Monocryl and Vicryl. These results highlight the critical role of thread selection in gastrointestinal surgeries, where prolonged exposure to bile and pancreatic juice can compromise the suture integrity and lead to postoperative complications. The insights gained from this study will contribute to improving the selection and application of absorbable threads in clinical settings. [ABSTRACT FROM AUTHOR]

Growing evidence has demonstrated the role of mutations of tumor biomarkers in diagnosing and treating epithelial ovarian cancer. This review aims to analyze recent literature on the correlation between tumor biomarkers and chemotherapy in nonmucinous ovarian cancer, providing suggestions for personalized treatment approaches. An extensive literature search was conducted to identify relevant studies and trials. BRCA1/2 mutations are central in homologous recombination repair deficiency (HRD) in ovarian cancer, but several other genetic mutations also contribute to varying cancer risks. While the role of MMR testing in ovarian cancer is debated, it is more commonly linked to non-serous ovarian cancer, often associated with Lynch syndrome. A significant proportion of ovarian cancer patients have HRD, affecting treatment decisions in both first-line (especially in advanced stages) and second-line therapy due to HRD's connection with platinum-based therapy and PARP inhibitors' response. However, validated genetic tests to identify HRD have not yet been universally implemented. There is no definitive therapeutic algorithm for advanced ovarian cancer, despite ongoing efforts and multiple proposed tools. Future research should focus on expanding the utility of biomarkers, reducing resistance, and increasing the actionable biomarker pool. [ABSTRACT FROM AUTHOR]

Double metal cyanide (DMC) complexes represent a unique family of materials with an open framework structure. The main current application of these complexes in chemical industry is their use as catalysts (DMCCs) of the ring-opening polymerization of propylene oxide (PO), yielding branched polyols, highly demanded in production of polyurethanes and surfactants. The actual problem of chemical fixing carbon dioxide from the atmosphere gave new impetus to the development of DMCCs, which turned out to be effective in oxirane/CO2 copolymerization. In recent years, new types and formulations of DMCCs were created, so that greater understanding of the reaction mechanisms was achieved and new fields of catalytic applications were found. In the present review, we summarized background and actual information about the synthesis, structure, and mechanisms of the action of DMCCs, as well as their application in the development of new materials and fine chemicals. [ABSTRACT FROM AUTHOR]

The synthetic peptide TAT-I24 (GRKKRRQRRRPPQCLAFYACFC) exerts antiviral activity against several double-stranded (ds) DNA viruses, including herpes simplex viruses, cytomegalovirus, some adenoviruses, vaccinia virus and SV40 polyomavirus. In the present study, in vitro profiling of this peptide was performed with the aim of characterizing and improving its properties for further development. As TAT-I24 contains three free cysteine residues, a potential disadvantageous feature, peptide variants with replacements or deletions of specific residues were generated and tested in various cell systems and by biochemical analyses. Some cysteine replacements had no impact on the antiviral activity, such as the deletion of cysteine 14, which also showed improved biochemical properties, while the cyclization of cysteines 14 and 20 had the most detrimental effect on antiviral activity. At concentrations below 20 µM, TAT-I24 and selected variants did not induce hemolysis in red blood cells (RBCs) nor modulated lipopolysaccharide (LPS)-induced release of cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), in human peripheral blood mononuclear cells (PBMCs). These data indicate that TAT-I24 or its peptide variants are not expected to cause unwanted effects on blood cells. [ABSTRACT FROM AUTHOR]

The human phosphatase and tensin homolog (PTEN) is a tumor suppressor. A slight deficiency in PTEN might cause cancer susceptibility and progression. Infection by the liver fluke Clonorchis sinensis could lead to persistent loss of PTEN in cholangiocarcinoma. However, the mechanism of PTEN loss and its malignant effect on cholangiocarcinoma have not yet been elucidated. Extracellular vesicles secreted by Clonorchis sinensis (CS-EVs) are rich in microRNAs (miRNAs) and can mediate communication between hosts and parasites. Herein, we delved into the miRNAs present in CS-EVs, specifically those that potentially target PTEN and modulate the progression of cholangiocarcinoma via ferroptosis mechanisms. CS-EVs were extracted by differential ultra-centrifugation for high-throughput sequencing of miRNA. Lentiviral vectors were used to construct stably transfected cell lines. Erastin was used to construct ferroptosis induction models. Finally, 36 miRNAs were identified from CS-EVs. Among them, csi-miR-96-5p inhibited PTEN expression according to the predictions and dual luciferase assay. The CCK-8 assay, xenograft tumor assays and transwell assay showed that csi-miR-96-5p overexpression and PTEN knockout significantly increased the proliferation and migration of cholangiocarcinoma cells and co-transfection of PTEN significantly reversed the effect. In the presence of erastin, the cell proliferation and migration ability of the negative transfection control group were significantly impaired, although they did not significantly change with transfection of csi-miR-96-5p and PTEN knockout, indicating that they obtained ferroptosis resistance. Mechanistically, csi-miR-96-5p and PTEN knockout significantly inhibited ferroptosis through a decrease in ferrous ion (Fe2+) and malondialdehyde (MDA), and an increase in glutathione reductase (GSH), Solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). In conclusion, loss of PTEN promoted the progression of cholangiocarcinoma via the ferroptosis pathway and csi-miR-96-5p delivered by CS-EVs may mediate this process. [ABSTRACT FROM AUTHOR]

This review contains data on a wide class of microporous materials with frameworks belonging to the sodalite topological type. Various methods for the synthesis of these materials, their structural and crystal chemical features, as well as physical and chemical properties are discussed. Specific properties of sodalite-related materials make it possible to consider they as thermally stable ionic conductors, catalysts and catalyst carriers, sorbents, ion exchangers for water purification, matrices for the immobilization of radionuclides and heavy metals, hydrogen and methane storage, and stabilization of chromophores and phosphors. It has been shown that the diversity of properties of sodalite-type materials is associated with the chemical diversity of their frameworks and extra-framework components, as well as with the high elasticity of the framework. [ABSTRACT FROM AUTHOR]

Much work has been dedicated to the quest to determine the structure–activity relationship in synthetic brassinosteroid (BR) analogs. Recently, it has been reported that analogs with phenyl or benzoate groups in the alkyl chain present activities comparable to those shown by natural BRs, depending on the nature of the substituent in the aromatic ring. However, as it is well known that the activity depends on the structure of the whole molecule, in this work, we have synthesized a series of compounds with the same substituted benzoate in the alkyl chain and a hydroxyl group at C3. The main goal was to compare the activities with analogs with -OH at C2 and C3. Additionally, a molecular-docking study and molecular dynamics simulations were performed to establish a correlation between the experimental and theoretical results. The synthesis of eight new BR analogs was described. All the analogs were fully characterized by spectroscopical methods. The bioactivity of these analogs was assessed using the rice lamina inclination test (RLIT) and the inhibition of the root and hypocotyl elongation of Arabidopsis thaliana. The results of the RLIT indicate that at the lowest tested concentration (1 × 10−8 M), in the BR analogs in which the aromatic ring was substituted at the para position with methoxy, the I and CN substituents were more active than brassinolide (50–72%) and 2–3 times more active than those analogs in which the substituent group was F, Cl or Br atoms. However, at the highest concentrations, brassinolide was the most active compound, and the structure–activity relationship changed. On the other hand, the results of the A. thaliana root sensitivity assay show that brassinolide and the analogs with I and CN as substituents on the benzoyl group were the most active compounds. These results are in line with those obtained via the RLIT. A comparison of these results with those obtained for similar analogs that had a hydroxyl group at C2 indicates the importance of considering the whole structure. The molecular-docking results indicate that all the analogs adopted a brassinolide-like orientation, while the stabilizing effect of the benzoate group on the interactions with the receptor complex provided energy binding values ranging between −10.17 and −13.17 kcal mol−1, where the analog with a nitrile group was the compound that achieved better contact with the amino acids present in the active site. [ABSTRACT FROM AUTHOR]

A preliminary in silico screening of 94 compounds, including colchicine, caffeine, gramine, and their derivatives, was conducted to identify potential herbicides, insecticides, and fungicides. Among the compounds tested, only gramine and its 13 derivatives exhibited potential activity. These compounds were further tested against eight species of insects, three species of weeds, and four species of fungi. All of the tested alkaloids were found to be ineffective as herbicides and insecticides, but they did exhibit some fungicidal activity. Four gramine derivatives showed some activity against Phytophthora infestans, Botrytis cinerea, Zymoseptoria tritici, and Fusarium culmorum. [ABSTRACT FROM AUTHOR]

Terpenes are plant secondary metabolites known for their anti-inflammatory and antioxidant activities. According to ethnobotanical knowledge, Rhododendron luteum Sweet was used in traditional medicine against inflammation. The present study was conducted to determine the triterpene profile and antioxidant and anti-inflammatory activity of supercritical CO2 (SC-CO2) extracts of Rhododendron luteum Sweet flower (RLF). An LC-APCI-MS/MS analysis showed the presence of eight pentacyclic triterpenes and one phytosterol in the extracts obtained with pure CO2 as well as CO2 with the addition of aqueous ethanol as a co-solvent. Among the compounds detected, oleanolic/ursolic acid, β-sitosterol and 3β-taraxerol were the most abundant. The extract obtained with pure SC-CO2 was additionally subjected to HS-SPME-GC-FID-MS, which revealed more than 100 volatiles, mainly eugenol, β-phenylethanol, dodecane, β-caryophyllene, estragole and (Z)- and (E)-cinnamyl alcohol, followed by δ-cadinene. The extracts demonstrated significant hyaluronidase inhibition and exhibited varying modes of lipoxygenase and xanthine oxidase inhibitory activities. The studies of RLF have shown that their SC-CO2 extracts can be a rich source of triterpenes with anti-inflammatory potential. [ABSTRACT FROM AUTHOR]

Over the last ten years, researchers' efforts have aimed to replace the classic linear economy model with the circular economy model, favoring green chemical and industrial processes. From this point of view, biologically active molecules, coming from plants, flowers and biomass, are gaining considerable value. In this study, firstly we focus on the development of a green protocol to obtain the purification of anthocyanins from the flower of Callistemon citrinus, based on simulation and on response surface optimization methodology. After that, we utilize them to manufacture and add new properties to bioplastics belonging to class 3, based on modified polyvinyl alcohol (PVA) with increasing amounts from 0.10 to 1.00%. The new polymers are analyzed to monitor morphological changes, optical properties, mechanical properties and antioxidant and antimicrobial activities. Fourier transform infrared spectroscopy (FTIR) spectra of the new materials show the characteristic bands of the PVA alone and a modification of the band at around 1138 cm−1 and 1083 cm−1, showing an influence of the anthocyanins' addition on the sequence with crystalline and amorphous structures of the starting materials, as also shown by the results of the mechanical tests. These last showed an increase in thickening (from 29.92 μm to approx. 37 μm) and hydrophobicity with the concomitant increase in the added anthocyanins (change in wettability with water from 14° to 31°), decreasing the poor water/moisture resistance of PVA that decreases its strength and limits its application in food packaging, which makes the new materials ideal candidates for biodegradable packaging to extend the shelf-life of food. The functionalization also determines an increase in the opacity, from 2.46 to 3.42 T%/mm, the acquisition of antioxidant activity against 2,2-diphenyl-1-picrylhdrazyl and 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) radicals and, in the ferric reducing power assay, the antimicrobial (bactericidal) activity against different Staphylococcus aureus strains at the maximum tested concentration (1.00% of anthocyanins). On the whole, functionalization with anthocyanins results in the acquisition of new properties, making it suitable for food packaging purposes, as highlighted by a food fresh-keeping test. [ABSTRACT FROM AUTHOR]

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and potentially life-threatening hematologic disorder caused by a somatic mutation in a relevant portion of hematopoietic stem cells. Mutation of the phosphatidylinositol glycan biosynthesis class A (PIGA) gene prevents the expression of cell-surface proteins, including the complement regulatory proteins CD55 and CD59. With decreased or a lack of CD55 and CD59 expression on their membranes, PNH red blood cells become susceptible to complement-mediated hemolysis (symptoms of which include anemia, dysphagia, abdominal pain, and fatigue), leading to thrombosis. State-of-the-art PNH treatments act by inhibiting the dysregulated complement at distinct points in the activation pathway: late at the C5 level (C5 inhibitors, eculizumab, ravulizumab, and crovalimab), centrally at the C3 level (C3/C3b inhibitors and pegcetacoplan), and early at the initiation and amplification of the alternative pathway (factor B inhibitor, iptacopan; factor D inhibitor, danicopan). Through their differing mechanisms of action, these treatments elicit varying profiles of disease control and offer valuable insights into the molecular underpinnings of PNH. This narrative review provides an overview of the mechanisms of action of the six complement inhibitors currently approved for PNH, with a focus on the C3/C3b-targeted therapy, pegcetacoplan. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) represents a significant global health burden, with high incidence and mortality rates worldwide. Recent progress in research highlights the distinct clinical and molecular characteristics of colon versus rectal cancers, underscoring tumor location's importance in treatment approaches. This article provides a comprehensive review of our current understanding of CRC epidemiology, risk factors, molecular pathogenesis, and management strategies. We also present the intricate cellular architecture of colonic crypts and their roles in intestinal homeostasis. Colorectal carcinogenesis multistep processes are also described, covering the conventional adenoma–carcinoma sequence, alternative serrated pathways, and the influential Vogelstein model, which proposes sequential APC, KRAS, and TP53 alterations as drivers. The consensus molecular CRC subtypes (CMS1-CMS4) are examined, shedding light on disease heterogeneity and personalized therapy implications. [ABSTRACT FROM AUTHOR]

The rapid detection of contaminants in water resources is vital for safeguarding the environment, where the use of eco-friendly materials for water monitoring technologies has become increasingly prioritized. In this context, the role of biocomposites in the development of a SERS sensor is reported in this study. Grafted chitosan was employed as a matrix support for Ag nanoparticles (NPs) for the surface-enhanced Raman spectroscopy (SERS). Chitosan (CS) was decorated with thiol and carboxylic acid groups by incorporating S-acetyl mercaptosuccinic anhydride (SAMSA) to yield CS-SAMSA. Then, Ag NPs were immobilized onto the CS-SAMSA (Ag@CS-SAMSA) and characterized by spectral methods (IR, Raman, NIR, solid state 13C NMR with CP-MAS, XPS, and TEM). Ag@CS-SAMSA was evaluated as a substrate for SERS, where methylene blue (MB) was used as a model dye adsorbate. The Ag@CS-SAMSA sensor demonstrated a high sensitivity (with an enhancement factor ca. 108) and reusability over three cycles, with acceptable reproducibility and storage stability. The Raman imaging revealed a large SERS effect, whereas the MB detection varied from 1–100 μM. The limits of detection (LOD) and quantitation (LOQ) of the biocomposite sensor were characterized, revealing properties that rival current state-of-the-art systems. The dye adsorption profiles were studied via SERS by fitting the isotherm results with the Hill model to yield the ΔG°ads for the adsorption process. This research demonstrates a sustainable dual-function biocomposite with tailored adsorption and sensing properties suitable for potential utility in advanced water treatment technology and environmental monitoring applications. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is an infectious disease that seriously affects human life and health. Despite centuries of efforts to control it, in recent years, the emergence of multidrug-resistant bacterial pathogens of M. tuberculosis due to various factors has exacerbated the disease, posing a serious threat to global health. Therefore, a new method to control M. tuberculosis is urgently needed. Phages, viruses that specifically infect bacteria, have emerged as potential biocontrol agents for bacterial pathogens due to their host specificity. In this study, a mycobacterium phage, Henu3, was isolated from soil around a hospital. The particle morphology, biological characteristics, genomics and phylogeny of Henu3 were characterized. Additionally, to explore the balance between phage resistance and stress response, phage Henu3-resistant strains 0G10 and 2E1 were screened by sequence passage and bidirectional validation methods, which significantly improved the sensitivity of phage to antibiotics (cefotaxime and kanamycin). By whole-genome re-sequencing of strains 0G10 and 2E1, 12 genes involved in cell-wall synthesis, transporter-encoded genes, two-component regulatory proteins and transcriptional regulatory factor-encoded genes were found to have mutations. These results suggest that phage Henu3 has the potential to control M. tuberculosis pathogens, and phage Henu3 has the potential to be a new potential solution for the treatment of M. tuberculosis infection. [ABSTRACT FROM AUTHOR]

Skeletal disorders, including fractures, osteoporosis, osteoarthritis, rheumatoid arthritis, and spinal degenerative conditions, along with associated spinal cord injuries, significantly impair daily life and impose a substantial burden. Many of these conditions are notably linked to inflammation, with some classified as inflammatory diseases. Pyroptosis, a newly recognized form of inflammatory cell death, is primarily triggered by inflammasomes and executed by caspases, leading to inflammation and cell death through gasdermin proteins. Emerging research underscores the pivotal role of pyroptosis in skeletal disorders. This review explores the pyroptosis signaling pathways and their involvement in skeletal diseases, the modulation of pyroptosis by other signals in these conditions, and the current evidence supporting the therapeutic potential of targeting pyroptosis in treating skeletal disorders, aiming to offer novel insights for their management. [ABSTRACT FROM AUTHOR]

This document is an editorial from the International Journal of Molecular Sciences discussing recent advances in plant somatic embryogenesis. Somatic embryogenesis is a process in which somatic cells undergo changes to form structures called somatic embryos, which can develop into plants. The article explores the applications of somatic embryogenesis in clonal propagation, genetic modification, and plant genome editing. It also discusses the use of somatic embryos in cryopreservation and the study of molecular mechanisms in plant development. The editorial highlights various studies on the induction of somatic embryogenesis, the role of transcription factors, the influence of auxins, and the practical applications of somatic embryogenesis in forest management and breeding programs. The authors conclude that while somatic embryogenesis is a powerful tool in plant biotechnology, further interdisciplinary research is needed to address remaining challenges. [Extracted from the article]

Immune evasion is a key phenomenon in understanding tumor recurrence, metastasis, and other critical steps in tumor progression. The tumor microenvironment (TME) is in constant flux due to the tumor's ability to release signals that affect it, while immune cells within it can impact cancer cell behavior. Cancer cells undergo several changes, which can change the enrichment of different immune cells and modulate the activity of existing immune cells in the tumor microenvironment. Cancer cells can evade immune surveillance by downregulating antigen presentation or expressing immune checkpoint molecules. High levels of tumor-infiltrating lymphocytes (TILs) correlate with better outcomes, and robust immune responses can control tumor growth. On the contrary, increased enrichment of Tregs, myeloid-derived suppressor cells, and M2-like anti-inflammatory macrophages can hinder effective immune surveillance and predict poor prognosis. Overall, understanding these immune evasion mechanisms guides therapeutic strategies. Researchers aim to modulate the TME to enhance immune surveillance and improve patient outcomes. In this review article, we strive to summarize the composition of the tumor immune microenvironment, factors affecting the tumor immune microenvironment (TIME), and different therapeutic modalities targeting the immune cells. This review is a first-hand reference to understand the basics of immune surveillance and immune evasion. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are relatively recently discovered biological nanoparticles that mediate intercellular communication. The development of new methods for the isolation and characterization of EVs is crucial to support further studies on these small and structurally heterogenous vesicles. New scalable production methods are also needed to meet the needs of future therapeutic applications. A reliable inline detection method for the EV manufacturing process is needed to ensure reproducibility and to identify any possible variations in real time. Here, we demonstrate the use of an inline Raman detector in conjunction with anion exchange chromatography for the isolation of EVs from human platelets. Anion-exchange chromatography can be easily coupled with multiple inline detectors and provides an alternative to size-based methods for separating EVs from similar-sized impurities, such as lipoprotein particles. Raman spectroscopy enabled us to identify functional groups in EV samples and trace EVs and impurities in different stages of the process. Our results show a notable separation of impurities from the EVs during anion-exchange chromatography and demonstrate the power of inline Raman spectroscopy. Compared to conventional EV analysis methods, the inline Raman approach does not require hands-on work and can provide detailed, real-time information about the sample and the purification process. [ABSTRACT FROM AUTHOR]

Drought is one of the major abiotic stresses that negatively affects plant growth and development. Ammopiptanthus mongolicus is an ecologically important shrub in the mid-Asia desert region and used as a model for abiotic tolerance research in trees. Protein phosphorylation participates in the regulation of various biological processes, however, phosphorylation events associated with drought stress signaling and response in plants is still limited. Here, we conducted a quantitative phosphoproteomic analysis of the response of A. mongolicus roots to short-term drought stress. Data are available via the iProx database with project ID IPX0000971000. In total, 7841 phosphorylation sites were found from the 2019 identified phosphopeptides, corresponding to 1060 phosphoproteins. Drought stress results in significant changes in the abundance of 103 phosphopeptides, corresponding to 90 differentially-phosphorylated phosphoproteins (DPPs). Motif-x analysis identified two motifs, including [pSP] and [RXXpS], from these DPPs. Functional enrichment and protein-protein interaction analysis showed that the DPPs were mainly involved in signal transduction and transcriptional regulation, osmotic adjustment, stress response and defense, RNA splicing and transport, protein synthesis, folding and degradation, and epigenetic regulation. These drought-corresponsive phosphoproteins, and the related signaling and metabolic pathways probably play important roles in drought stress signaling and response in A. mongolicus roots. Our results provide new information for understanding the molecular mechanism of the abiotic stress response in plants at the posttranslational level. [ABSTRACT FROM AUTHOR]

Chemical residues in food pose health risks such as cancer and liver issues. This has driven the search for safer natural alternatives to synthetic fungicides and preservatives. The aim of this study was to characterize the chemical composition of the essential oils (EO), determine the polyphenolic contents, and evaluate the in vitro antioxidant and antifungal activities of methanol extracts (ME), essential oils (EO), and powders from Rosmarinus officinalis L. (rosemary) and Thymus ciliatus (Desf) Benth. (thyme) from the M'sila region, Algeria. The chemical composition of the EOs was determined by GC-MS. R. officinalis EO was composed of 31 components, mainly camphor (41.22%), camphene (18.14%), and α-pinene (17.49%); T. ciliatus EO was composed of 58 components, mainly, in percentage, α-pinene (22.18), myrcene (13.13), β-pinene (7.73), β-caryophyllene (10.21), and germacrene D (9.90). The total phenols and flavonoids were determined spectrophotometrically, and the rosemary ME was found to possess the highest polyphenolic content (127.1 ± 2.40 µg GAE/mg), while the thyme ME had the highest flavonoid content (48.01 ± 0.99 µg QE/mg). The antioxidant activity was assessed using three methods: rosemary ME was the most potent, followed by DPPH (IC50 = 13.43 ± 0.14 µg/mL), β-carotene/linoleic acid (IC50 = 39.01 ± 2.16 μg/mL), and reducing power (EC50 = 15.03 ± 1.43 µg/mL). Antifungal activity was assessed for 32 pathogenic and foodborne fungi. Four methods were applied to the solid medium. Incorporating the powdered plant into the culture medium (at 10%) reduced the fungal growth to greater than 50% in 21.88% and 6.25% of all fungal isolates, for R. officinalis and T. ciliatus, respectively. The ME, applied by the well diffusion method (0.1 g/mL), was less effective. Different concentrations of EO were tested. Incorporating the EO into the culture medium (1500 μL/L) inhibited 50% of the molds to levels of 50 and 75% for R. officinalis and T. ciliatus, respectively, with the complete inhibition of four fungi. Fumigated EO (15 μL) inhibited 65% of the molds to levels of 65 and 81.25% for R. officinalis and T. ciliatus, respectively, with the complete inhibition of five fungi. There was little to no sporulation in conjunction with the inhibition. Our results revealed some of the potential of the studied plants to fight foodborne molds and presented their promising characteristics as a source of alternatives to chemical pesticides and synthetic preservatives. Further studies are needed to find adequate application techniques in the food safety area. [ABSTRACT FROM AUTHOR]

Colon cancer, one of the most common and fatal cancers worldwide, is characterized by stepwise accumulation of specific genetic alterations in tumor suppressor genes or oncogenes, leading to tumor growth and metastasis. HIPK2 (homeodomain-interacting protein kinase 2) is a serine/threonine protein kinase and a "bona fide" oncosuppressor protein. Its activation inhibits tumor growth mainly by promoting apoptosis, while its inactivation increases tumorigenicity and resistance to therapies of many different cancer types, including colon cancer. HIPK2 interacts with many molecular pathways by means of its kinase activity or transcriptional co-repressor function modulating cell growth and apoptosis, invasion, angiogenesis, inflammation and hypoxia. HIPK2 has been shown to participate in several molecular pathways involved in colon cancer including p53, Wnt/β-catenin and the newly identified nuclear factor erythroid 2 (NF-E2) p45-related factor 2 (NRF2). HIPK2 also plays a role in tumor–host interaction in the tumor microenvironment (TME) by inducing angiogenesis and cancer-associated fibroblast (CAF) differentiation. The aim of this review is to assess the role of HIPK2 in colon cancer and the underlying molecular pathways for a better understanding of its involvement in colon cancer carcinogenesis and response to therapies, which will likely pave the way for novel colon cancer therapies. [ABSTRACT FROM AUTHOR]

There is increasing evidence that vitamin D (VitD) supplementation may reduce inflammation in individuals with multiple sclerosis (MS). The aim of this study was to evaluate the effect of different doses of VitD on selected markers of inflammation in patients with relapsing–remitting MS (RRMS). Participants were divided depending on the supplemented dose of VitD into a high-dose (2000 IU/d; HD) group and a low-dose (15,960 IU/month; LD) group (n = 23 and n = 29, respectively). The concentration of 25(OH)D and the levels of CXCL16, PTX3, ALCAM, IL-1RA, and OPG were measured initially and after six months of VitD supplementation in blood serum. A significant increase in the concentrations of CXCL16, PTX3, and OPG was observed during the study (p = 0.02, p = 0.01, and p < 0.01, respectively). Furthermore, a higher increase in PTX3 and OPG in the LD group was observed (p = 0.04 and p = 0.03, respectively). A significant positive correlation was observed between the 25(OH)D serum concentration and PTX3 (R = 0.28, p < 0.05) and OPG (R = 0.28, p < 0.05) only at the beginning of the study. In patients with RRMS, such doses of VitD might be too low to induce obvious beneficial effects on the pro-inflammatory and inflammatory balance. [ABSTRACT FROM AUTHOR]

In theory, two extreme forms of substances exist: the pure form and the single-molecule mixture form. The latter contains a mixture of molecules with molecularly different structures. Inspired by the "chemical space" concept, in this paper, I report a study of the single-molecule mixture state that combines model construction and mathematical analysis, obtaining some interesting results. These results provide theoretical evidence that the single-molecule mixture state may indeed exist in realistic synthetic or natural polymer systems. [ABSTRACT FROM AUTHOR]

Growth differentiation factor 15 (GDF-15) is a multifunctional cytokine that belongs to the transforming growth factor-beta (TGF-β) superfamily. GDF-15 is involved in immune tolerance and is elevated in several acute and chronic stress conditions, often correlating with disease severity and patient prognosis in cancer172 and metabolic and cardiovascular disorders. Despite these clinical associations, the molecular mechanisms orchestrating its effects remain to be elucidated. The effects of GDF-15 are pleiotropic but cell-specific and dependent on the microenvironment. While GDF-15 expression can be stimulated by inflammatory mediators, its predominant effects were reported as anti-inflammatory and pro-fibrotic. The role of GDF-15 in the macrophage system has been increasingly investigated in recent years. Macrophages produce high levels of GDF-15 during oxidative and lysosomal stress, which can lead to fibrogenesis and angiogenesis at the tissue level. At the same time, macrophages can respond to GDF-15 by switching their phenotype to a tolerogenic one. Several GDF-15-based therapies are under development, including GDF-15 analogs/mimetics and GDF-15-targeting monoclonal antibodies. In this review, we summarize the major physiological and pathological contexts in which GDF-15 interacts with macrophages. We also discuss the major challenges and future perspectives in the therapeutic translation of GDF-15. [ABSTRACT FROM AUTHOR]

The incidence of nonalcoholic fatty liver disease (NAFLD), or metabolic dysfunction-associated fatty liver disease (MAFLD), is increasing in adults and children. Unfortunately, effective pharmacological treatments remain unavailable. Single nucleotide polymorphisms (SNPs) in the patatin-like phospholipase domain-containing protein (PNPLA3 I148M) have the most significant genetic association with the disease at all stages of its progression. A roadblock to identifying potential treatments for PNPLA3-induced NAFLD is the lack of a human cell platform that recapitulates the PNPLA3 I148M-mediated onset of lipid accumulation. Hepatocyte-like cells were generated from PNPLA3−/− and PNPLA3I148M/M-induced pluripotent stem cells (iPSCs). Lipid levels were measured by staining with BODIPY 493/503 and were found to increase in PNPLA3 variant iPSC-derived hepatocytes. A small-molecule screen identified multiple compounds that target Src/PI3K/Akt signaling and could eradicate lipid accumulation in these cells. We found that drugs currently in clinical trials for cancer treatment that target the same pathways also reduced lipid accumulation in PNPLA3 variant cells. [ABSTRACT FROM AUTHOR]

Endometriosis is a chronic inflammatory disease characterized by the presence of endometrial-like tissue outside the uterine cavity, causing pain and infertility. Despite the rather unclear etiopathogenesis, recent studies suggest the involvement of the immune system in the development and progression of endometriosis. The role of the PD-1/PD-L1 axis in the modulation of the immune response in this disease seems to be particularly interesting. This preliminary study aimed to investigate the expression of PD-1 and PD-L1 on T and B lymphocytes in peripheral blood in patients with endometriosis to assess their potential impact on disease progression. Our study involved peripheral blood samples from 80 patients diagnosed with endometriosis and 20 healthy women as a control group were analyzed. Flow cytometry was used to assess the expression of PD-1 and PD-L1 on T and B lymphocytes, and enzyme-linked immunosorbent assays were used to assess their soluble forms in serum and peritoneal fluid.in our research we observe significantly higher expression of PD-1 and PD-L1 on T and B lymphocytes was found in patients with endometriosis compared to the control group. Higher expression of both tested molecules correlated with the stage of endometriosis. The results of our preliminary studies indicate a potential role of the PD-1/PD-L1 axis in the modulation of the immune response in endometriosis. Modified expression of these proteins may contribute to immune evasion by ectopic tissues, supporting their survival and proliferation. These findings suggest that targeting PD-1/PD-L1 could be explored as a therapeutic option for the treatment of endometriosis, though further research with larger sample sizes is necessary to confirm these results and clarify the role of PD-1/PD-L1 in the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Thyroid cancer diagnosis primarily relies on imaging techniques and cytological analyses. In cases where the diagnosis is uncertain, the quantification of molecular markers has been incorporated after cytological examination. This approach helps physicians to make surgical decisions, estimate cancer aggressiveness, and monitor the response to treatments. Despite the availability of commercial molecular tests, their widespread use has been hindered in our experience due to cost constraints and variability between them. Thus, numerous groups are currently evaluating new molecular markers that ultimately will lead to improved diagnostic certainty, as well as better classification of prognosis and recurrence. In this review, we start reviewing the current preoperative testing methodologies, followed by a comprehensive review of emerging molecular markers. We focus on micro RNAs, long non-coding RNAs, and mitochondrial (mt) signatures, including mtDNA genes and circulating cell-free mtDNA. We envision that a robust set of molecular markers will complement the national and international clinical guides for proper assessment of the disease. [ABSTRACT FROM AUTHOR]

Different developmental genes shape frequent dynamic inter-chromosomal contacts with rDNA units in human and Drosophila cells. In the course of differentiation, changes in these contacts occur, coupled with changes in the expression of hundreds of rDNA-contacting genes. The data suggest a possible role of nucleoli in the global regulation of gene expression. However, the mechanism behind the specificity of these inter-chromosomal contacts, which are rebuilt in every cell cycle, is not yet known. Here, we describe the strong association of rDNA-contacting genes with numerous long intergenic non-coding RNAs (lincRNAs) in HEK293T cells and in initial and differentiated K562 cells. We observed that up to 600 different lincRNAs were preferentially co-expressed with multiple overlapping sets of rDNA-contacting developmental genes, and there was a strong correlation between the genomic positions of rDNA-contacting genes and lincRNA mappings. These two findings suggest that lincRNAs might guide the corresponding developmental genes toward rDNA clusters. We conclude that the inter-chromosomal interactions of rDNA-contacting genes with nucleoli might be guided by lincRNAs, which might physically link particular genomic regions with rDNA clusters. [ABSTRACT FROM AUTHOR]

In this narrative review, we attempt to provide an overview of the evidence regarding the role of estrogen (receptors) in cutaneous melanoma (CM). We reviewed 68 studies and 4 systematic reviews and meta-analyses published from 2002 up to and including 2022. The prevailing presence of estrogen receptor β (ERβ) instead of estrogen receptor α (ERα) in CM is notable, with ERβ potentially playing a protective role and being less frequently detected in progressive cases. While men with CM generally experience a less favorable prognosis, this distinction may become negligible with advancing age. The role of oral contraceptives (OC) and hormone replacement therapy (HRT) in CM remains controversial. However, recent studies tend to associate the use of these exogenous hormones with a heightened risk of CM, mostly only when using estrogen therapy and not in combination with progesterone. On the contrary, the majority of studies find no substantial influence of in vitro fertilization (IVF) treatment on CM risk. Reproductive factors, including younger age at first childbirth, higher parity, and shorter reproductive life, show conflicting evidence, with some studies suggesting a lower CM risk. We suggest an important role for estrogens in CM. More research is needed, but the integration of estrogens and targeting the estrogen receptors in melanoma therapy holds promise for future developments in the field. [ABSTRACT FROM AUTHOR]

The early detection of gynecological cancers, which is critical for improving patient survival rates, is challenging because of the vague early symptoms and the diagnostic limitations of current approaches. This comprehensive review delves into the game-changing potential of infrared (IR) spectroscopy, a noninvasive technology used to transform the landscape of cancer diagnosis in gynecology. By collecting the distinctive vibrational frequencies of chemical bonds inside tissue samples, Fourier-transform infrared (FTIR) spectroscopy provides a 'molecular fingerprint' that outperforms existing diagnostic approaches. We highlight significant advances in this field, particularly the identification of discrete biomarker bands in the mid- and near-IR spectra. Proteins, lipids, carbohydrates, and nucleic acids exhibited different absorption patterns. These spectral signatures not only serve to distinguish between malignant and benign diseases, but also provide additional information regarding the cellular changes associated with cancer. To underscore the practical consequences of these findings, we examined studies in which IR spectroscopy demonstrated exceptional diagnostic accuracy. This review supports the use of IR spectroscopy in normal clinical practice, emphasizing its capacity to detect and comprehend the intricate molecular underpinnings of gynecological cancers. [ABSTRACT FROM AUTHOR]