Functional selection in SH3-mediated activation of the PI3 kinase.

The phosphoinositide-3 kinase (PI3K), a heterodimeric enzyme, plays a pivotal role in cellular metabolism and survival. Its deregulation is associated with major human diseases, particularly cancer. The p85 regulatory subunit of PI3K binds to the catalytic p110 subunit via its C-terminal domains, stabilising it in an inhibited state. Certain Src homology 3 (SH3) domains can activate p110 by binding to the proline-rich (PR) 1 motif located at the N-terminus of p85. However, the mechanism by which this N-terminal interaction activates the C-terminally bound p110 remains elusive. Moreover, the intrinsically poor ligand selectivity of SH3 domains raises the question of how they can control PI3K. Combining structural, biophysical, and functional methods, we demonstrate that the answers to both these unknown issues are linked: PI3K-activating SH3 domains engage in additional "tertiary" interactions with the C-terminal domains of p85, thereby relieving their inhibition of p110. SH3 domains lacking these tertiary interactions may still bind to p85 but cannot activate PI3K. Thus, p85 uses a functional selection mechanism that precludes nonspecific activation rather than nonspecific binding. This separation of binding and activation may provide a general mechanism for how biological activities can be controlled by promiscuous protein-protein interaction domains.

SOS1 tonoplast neo-localization and the RGG protein SALTY are important in the extreme salinity tolerance of Salicornia bigelovii.

The identification of genes involved in salinity tolerance has primarily focused on model plants and crops. However, plants naturally adapted to highly saline environments offer valuable insights into tolerance to extreme salinity. Salicornia plants grow in coastal salt marshes, stimulated by NaCl. To understand this tolerance, we generated genome sequences of two Salicornia species and analyzed the transcriptomic and proteomic responses of Salicornia bigelovii to NaCl. Subcellular membrane proteomes reveal that SbiSOS1, a homolog of the well-known SALT-OVERLY-SENSITIVE 1 (SOS1) protein, appears to localize to the tonoplast, consistent with subcellular localization assays in tobacco. This neo-localized protein can pump Na+ into the vacuole, preventing toxicity in the cytosol. We further identify 11 proteins of interest, of which SbiSALTY, substantially improves yeast growth on saline media. Structural characterization using NMR identified it as an intrinsically disordered protein, localizing to the endoplasmic reticulum in planta, where it can interact with ribosomes and RNA, stabilizing or protecting them during salt stress.

Shielding Effects Provide a Dominant Mechanism in J-Aggregation-Induced Photoluminescence Enhancement of Carbon Nanotubes.

The unique photophysical properties of single-walled carbon nanotubes (SWCNTs) exhibit great potential for bioimaging applications. This led to extensive exploration of photosensitization methods to improve their faint shortwave infrared (SWIR) photoluminescence. Here, we report the mechanisms of SWCNT-assisted J-aggregation of cyanine dyes and the associated photoluminescence enhancement of SWCNTs in the SWIR spectral region. Surprisingly, we found that excitation energy transfer between the cyanine dyes and SWCNTs makes a negligible contribution to the overall photoluminescence enhancement. Instead, the shielding of SWCNTs from the surrounding water molecules through hydrogen bond-assisted macromolecular reorganization of ionic surfactants triggered by counterions and the physisorption of the dye molecules on the side walls of SWCNTs play a primary role in the photoluminescence enhancement of SWCNTs. We observed 2 orders of magnitude photoluminescence enhancement of SWCNTs by optimizing these factors. Our findings suggest that the proper shielding of SWCNTs is the critical factor for their photoluminescence enhancement, which has important implications for their application as imaging agents in biological settings.

Metabolomics-based analysis of the diatom Cheatoceros tenuissimus combining NMR and GC-MS techniques.

Metabolomics, a recent addition to omics sciences, studies small molecules across plants, animals, humans, and marine organisms. Nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS) are widely used in those studies, including microalgae metabolomics. NMR is non-destructive and highly reproducible but has limited sensitivity, which could be supplemented by joining GC-MS analysis. Extracting metabolites from macromolecules requires optimization for trustworthy results. Different extraction methods yield distinct profiles, emphasizing the need for optimization. The results indicated that the optimized extraction procedure successfully identified NMR and GC-MS-based metabolites in MeOH, CHCl3, and H2O extraction solvents. The findings represented the spectral information related to carbohydrates, organic molecules, and amino acids from the water-soluble metabolites fraction and a series of fatty acid chains, lipids, and sterols from the lipid fraction. Our study underscores the benefit of combining NMR and GC-MS techniques to comprehensively understand microalgae metabolomes, including high and low metabolite concentrations and abundances.•In this study, we focused on optimizing the extraction procedure and combining NMR and GC-MS techniques to overcome the low NMR sensitivity and the different detected range limits of NMR and GC-MS.•We explored metabolome diversity in a tropical strain of the small cells' diatom Cheatoceros tenuissimus.

Electrospun Cu-Co ferrite nanofibers: synthesis, structure, optical and magnetic properties, and anti-cancer activity.

In this study, we investigated Cu-Co ferrite nanofibers (NFs) that were synthesized for the first time employing the electrospinning technique. The structure, phase purity and crystallite size of all the prepared NFs were revealed by powder X-ray diffraction (PXRD) analysis. The NFs crystallized in the Fd3̄m (no. 227) space group and the cation distribution arrangement over distinct sites in their structure was analyzed. Scanning electron microscopy (SEM) together with energy-dispersive X-ray (EDX) spectroscopy analysis showed the microstructure of the NFs and verified their expected chemical compositions. High-resolution transmission electron microscopy (TEM) images confirmed the fibrous nature and the construction of the NFs. The band gap energies derived from the UV-vis reflectance spectra showed a blue shift with an increase in the amount of Cu in the sample from 1.42 eV to 1.86 eV. Magnetization (M) as a function of magnetic field (H) measurements performed at ambient and low temperatures showed the ferrimagnetic behavior of all the NFs. The magnetic parameters including coercivity (Hc), saturation magnetization (Ms), remanent magnetization (Mr), and squareness ratio were determined from the recorded magnetization curves. At 300 K, Ms was reduced from 78.8 to 42.4 emu g-1, Mr reduced from 22.8 to 7.6 emu g-1 and the Bohr magneton reduced from 3.3 to 1.8µB with an increase in the content of Cu in the samples. The same trend was observed at 10 K, where Ms was reduced from 93.7 to 50.9 emu g-1, Mr reduced from 60.9 to 35.9 emu g-1 and the Bohr magneton reduced from 3.94 to 2.16µB. Alternatively, Hc has the highest values for x = 0 (850 Oe at 300 K and 5220 Oe at 10 K) and x = 0.6 (800 Oe at 300 K and 5400 Oe at 10 K). The anti-cancer activity of the NFs was evaluated using the MTT cell viability assay, showing a reduction in the viability of both HCT-116 and HeLa cancer cells compared to non-cancerous HEK-293 cells after treatment with the NFs. Apoptotic activity was examined by DAPI staining, where treatment with the NFs induced chromatin condensation and nuclear disintegration in HCT-116 cells.

Mitochondrial dysfunction route as a possible biomarker and therapy target for human cancer.

Mitochondria are vital organelles found within living cells and have signalling, biosynthetic, and bioenergetic functions. Mitochondria play a crucial role in metabolic reprogramming, which is a characteristic of cancer cells and allows them to assure a steady supply of proteins, nucleotides, and lipids to enable rapid proliferation and development. Their dysregulated activities have been associated with the growth and metastasis of different kinds of human cancer, particularly ovarian carcinoma. In this review, we briefly demonstrated the modified mitochondrial function in cancer, including mutations in mtDNA, reactive oxygen species production, dynamics, apoptosis of cells, autophagy, and calcium excess to maintain cancer genesis, progression, and metastasis. Furthermore, the mitochondrial dysfunction pathway for some genomic, proteomic, and metabolomics modifications in ovarian cancer has been studied. Additionally, ovarian cancer has been linked to targeted therapies and biomarkers found through various alteration processes underlying mitochondrial dysfunction, notably targeting reactive oxygen species, metabolites, rewind metabolic pathways, and chemo-resistant ovarian carcinoma cells.

Applications of biaryl cyclization in the synthesis of cyclic enkephalin analogs with a highly restricted flexibility.

A series of 10 cyclic, biaryl analogs of enkephalin, with Tyr or Phe residues at positions 1 and 4, were synthesized according to the Miyaura borylation and Suzuki coupling methodology. Biaryl bridges formed by side chains of the two aromatic amino acid residues are of the meta-meta, meta-para, para-meta, and para-para configuration. Conformational properties of the peptides were studied by CD and NMR. CD studies allowed only to compare conformations of individual peptides while NMR investigations followed by XPLOR calculations provided detailed information on their conformation. Reliability of the XPLOR calculations was confirmed by quantum chemical ones performed for one of the analogs. No intramolecular hydrogen bonds were found in all the peptides. They are folded and adopt the type IV ß-turn conformation. Due to a large steric strain, the aromatic carbon atoms forming the biaryl bond are distinctly pyramidalized. Seven of the peptides were tested in vitro for their affinity for the µ-opioid receptor.

Heat shock proteins as a key defense mechanism in poultry production under heat stress conditions.

Over the past years, the poultry industry has been assigned to greater production performance but has become highly sensitive to environmental changes. The average world temperature has recently risen and is predicted to continue rising. In open-sided houses, poultry species confront high outside temperatures, which cause heat stress (HS) problems. Cellular responses are vital in poultry, as they may lead to identifying confirmed HS biomarkers. Heat shock proteins (HSP) are highly preserved protein families that play a significant role in cell function and cytoprotection against various stressors, including HS. The optimal response in which the cell survives the HS elevates HSP levels that prevent cellular proteins from damage caused by HS. The HSP have chaperonic action to ensure that stress-denatured proteins are folded, unfolded, and refolded. The HSP70 and HSP90 are the primary HSP in poultry with a defensive function during HS. HSP70 was the optimal biological marker for assessing HS among the HSP studied. The current review attempts to ascertain the value of HSP as a heat stress defense mechanism in poultry.

Adjuvant Novel Nanocarrier-Based Targeted Therapy for Lung Cancer.

Lung cancer has the lowest survival rate due to its late-stage diagnosis, poor prognosis, and intra-tumoral heterogeneity. These factors decrease the effectiveness of treatment. They release chemokines and cytokines from the tumor microenvironment (TME). To improve the effectiveness of treatment, researchers emphasize personalized adjuvant therapies along with conventional ones. Targeted chemotherapeutic drug delivery systems and specific pathway-blocking agents using nanocarriers are a few of them. This study explored the nanocarrier roles and strategies to improve the treatment profile's effectiveness by striving for TME. A biofunctionalized nanocarrier stimulates biosystem interaction, cellular uptake, immune system escape, and vascular changes for penetration into the TME. Inorganic metal compounds scavenge reactive oxygen species (ROS) through their photothermal effect. Stroma, hypoxia, pH, and immunity-modulating agents conjugated or modified nanocarriers co-administered with pathway-blocking or condition-modulating agents can regulate extracellular matrix (ECM), Cancer-associated fibroblasts (CAF),Tyro3, Axl, and Mertk receptors (TAM) regulation, regulatory T-cell (Treg) inhibition, and myeloid-derived suppressor cells (MDSC) inhibition. Again, biomimetic conjugation or the surface modification of nanocarriers using ligands can enhance active targeting efficacy by bypassing the TME. A carrier system with biofunctionalized inorganic metal compounds and organic compound complex-loaded drugs is convenient for NSCLC-targeted therapy.

Anticancer effect and laser photostability of ternary graphene oxide/chitosan/silver nanocomposites on various cancer cell lines.

Aims: The development of nanocomposites (NCs) of antitumor activity provides a new paradigm for fighting cancer. Here, a novel NC of green synthetic silver nanoparticles (AgNPs), graphene oxide (GO) and chitosan (Cs) NPs was developed. Materials & methods: The prepared GO/Cs/Ag NCs were analyzed using various techniques. Cytotoxicity of the NCs was evaluated against different cancer cell lines by Sulforhodamine B (SRB) assay. Results: GO/Cs/Ag NCs are novel and highly stable. UV-Vis showed two peaks at 227 and 469 nm, indicating the decoration of AgNPs on the surface of GO/Cs NPs. All tested cell lines were affected by GO/Cs NPs and GO/Cs/Ag NCs. Conclusion: The results indicate that GO/Cs/Ag NCs were present on tested cell lines and are a promising candidate for cancer therapy.

Exploring nature's hidden treasure: Unraveling the untapped phytochemical and pharmacological potentials of Clinopodium vulgare L. - A hidden gem in the Lamiaceae family.

Folk medicine, rooted in historical practice, has long been used for medicinal purposes, emphasizing the need to ensure the safety, quality, and efficacy of herbal medicines. This imperative has grown over time, prompting collaborative efforts to document historical records and preserve invaluable knowledge of medicinal plants. The Lamiaceae (Labiatae) family, renowned for its rich assortment of medicinal plants characterized by high concentrations of volatile oils, stands out in this regard. This review focuses on Clinopodium vulgare (C. vulgare) L., commonly known as wild basil or basil thyme, a significant species within the Lamiaceae family found across diverse global regions. C. vulgare boasts a storied history of application in treating various ailments, such as gastric ulcers, diabetes, and inflammation, dating back to ancient times. Rigorous research has substantiated its pharmacological properties, revealing its antioxidant, antiviral, antibacterial, anti-inflammatory, anticancer, antihypertensive, and enzyme-inhibitory effects. This comprehensive review provides an insightful overview of the Lamiaceae family, elucidates the extraction methods employed to obtain medicinal compounds, explores the phytoconstituents present in C. vulgare, and systematically details its diverse pharmacological properties. Additionally, the review delves into considerations of toxicity. By synthesizing this wealth of information, this study opens avenues for the potential therapeutic applications of C. vulgare. The practical value of this research lies in its contribution to the understanding of medicinal plants, mainly focusing on the pharmacological potential of C. vulgare. This exploration enriches our knowledge of traditional medicine and paves the way for innovative therapeutic approaches, offering promising prospects for future drug development. As the demand for natural remedies continues to increase, this work provides a valuable resource for researchers, practitioners, and stakeholders in herbal medicine and pharmacology.

New 1,3,4-Thiadiazole Derivatives as α-Glucosidase Inhibitors: Design, Synthesis, DFT, ADME, and In Vitro Enzymatic Studies.

Diabetes is an emerging disorder in the world and is caused due to the imbalance of insulin production as well as serious effects on the body. In search of a better treatment for diabetes, we designed a novel class of 1,3,4-thiadiazole-bearing Schiff base analogues and assessed them for the α-glucosidase enzyme. In the series (1-12), compounds are synthesized and 3 analogues showed excellent inhibitory activity against α-glucosidase enzymes in the range of IC50 values of 18.10 ± 0.20 to 1.10 ± 0.10 µM. In this series, analogues 4, 8, and 9 show remarkable inhibition profile IC50 2.20 ± 0.10, 1.10 ± 0.10, and 1.30 ± 0.10 µM by using acarbose as a standard, whose IC50 is 11.50 ± 0.30 µM. The structure of the synthesized compounds was confirmed through various spectroscopic techniques, such as NMR and HREI-MS. Additionally, molecular docking, pharmacokinetics, cytotoxic evaluation, and density functional theory study were performed to investigate their behavior.

Synthesis and characterization of bis-amide SSE1917 as a microtubule-stabilizing anticancer agent.

Microtubule dynamics are critical for spindle assembly and chromosome segregation during cell division. Pharmacological inhibition of microtubule dynamics in cells causes prolonged mitotic arrest, resulting in apoptosis, an approach extensively employed in treating different types of cancers. The present study reports the synthesis of thirty-two novel bis-amides (SSE1901-SSE1932) and the evaluation of their antiproliferative activities. N-(1-oxo-3-phenyl-1-(phenylamino)propan-2-yl)benzamide (SSE1917) exhibited the most potent activity with GI50 values of 0.331 ± 0.01 µM in HCT116 colorectal and 0.48 ± 0.27 µM in BT-549 breast cancer cells. SSE1917 stabilized microtubules in biochemical and cellular assays, bound to taxol site in docking studies, and caused aberrant mitosis and G2/M arrest in cells. Prolonged treatment of cells with the compound increased p53 expression and triggered apoptotic cell death. Furthermore, SSE1917 suppressed the growth of both mouse and patient-derived human colon cancer organoids, highlighting its potential therapeutic value as an anticancer agent.

Current insights and molecular docking studies of HIV-1 reverse transcriptase inhibitors.

Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS), a lethal disease that is prevalent worldwide. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS) data, 38.4 million people worldwide were living with HIV in 2021. Viral reverse transcriptase (RT) is an excellent target for drug intervention. Nucleoside reverse transcriptase inhibitors (NRTIs) were the first class of approved antiretroviral drugs. Later, a new type of non-nucleoside reverse transcriptase inhibitors (NNRTIs) were approved as anti-HIV drugs. Zidovudine, didanosine, and stavudine are FDA-approved NRTIs, while nevirapine, efavirenz, and delavirdine are FDA-approved NNRTIs. Several agents are in clinical trials, including apricitabine, racivir, elvucitabine, doravirine, dapivirine, and elsulfavirine. This review addresses HIV-1 structure, replication cycle, reverse transcription, and HIV drug targets. This study focuses on NRTIs and NNRTIs, their binding sites, mechanisms of action, FDA-approved drugs and drugs in clinical trials, their resistance and adverse effects, their molecular docking studies, and highly active antiretroviral therapy (HAART).

Electronic cigarette vapor disrupts key metabolic pathways in human lung epithelial cells.

The steady increase in the use of electronic cigarettes (ECs) has reached an epidemic level, increasing mortality and morbidity, mainly due to pulmonary toxicity. Several mechanisms are involved in EC-induced toxicity, including oxidative stress and increased inflammation. Concurrently, the integrity of cellular metabolism is essential for cellular homeostasis and mitigation of toxic insults. However, the effects of EC on cellular metabolism remain largely unknown. In this study, we investigated the metabolic changes induced by EC in human lung epithelial cells (A549) using an untargeted metabolomics approach. A549 cells were exposed to increasing EC vapor extract concentrations, and cell viability, oxidative stress, and metabolomic changes were assessed. Our findings show that ECs induce cell death and increase oxidative stress in a concentration-dependent manner. Metabolomic studies demonstrated that ECs induce unique metabolic changes in key cellular metabolic pathways. Our results revealed that exposure to ECs induced clear segregation in metabolic responses which is driven significantly by number of essential metabolites such as aminoacids, fatty acids, glutathione, and pyruvate. Interstingly, our metabolomics results showed that each concentration of ECs induced unqiues pattern of metabolic changes, suggesting the complexity of ECs induced cytotoxcity. Disrupted metabolites were linked to essential cellular pathways, such as fatty acid biosynthesis, as well as glutathione, pyruvate, nicotinate and nicotinamide, and amino acid metabolisms. These results highlight the potential adverse effects of ECs on cellular metabolism and emphasize the need for further research to fully understand the long-term consequences of EC use. Overall, this study demonstrates that ECs not only induce cell death and oxidative stress but also disrupt cellular metabolism in A549 lung epithelial cells.

Novel 8-Methoxycoumarin-3-Carboxamides with potent anticancer activity against liver cancer via targeting caspase-3/7 and ß-tubulin polymerization.

In the present study, we explored the potential of coumarin-based compounds, known for their potent anticancer properties, by designing and synthesizing a novel category of 8-methoxycoumarin-3-carboxamides. Our aim was to investigate their antiproliferative activity against liver cancer cells. Toward this, we developed a versatile synthetic approach to produce a series of 8-methoxycoumarin-3-carboxamide analogues with meticulous structural features. Assessment of their antiproliferative activity demonstrated their significant inhibitory effects on the growth of HepG2 cells, a widely studied liver cancer cell line. Among screened compounds, compound 5 exhibited the most potent antiproliferative activity among the screened compounds (IC50 = 0.9 µM), outperforming the anticancer drug staurosporine (IC50 = 8.4 µM), while showing minimal impact on normal cells. The flow cytometric analysis revealed that compound 5 induces cell cycle arrest during the G1/S phase and triggers apoptosis in HepG2 cells by increasing the percentage of cells arrested in the G2/M and pre-G1 phases. Annexin V-FITC/PI screening further supported the induction of apoptosis without significant necrosis. Further, compound 5 exhibited the ability to activate caspase3/7 protein and substantially inhibited ß-tubulin polymerization activity in HepG2 cells. Finally, molecular modelling analysis further affirmed the high binding affinity of compound 5 toward the active cavity of ß-tubulin protein, suggesting its mechanistic involvement. Collectively, our findings highlight the therapeutic potential of the presented class of coumarin analogues, especially compound 5, as promising candidates for the development of effective anti-hepatocellular carcinoma agents.

Improving quality of analysis by suppression of unwanted signals through band-selective excitation in NMR spectroscopy for metabolomics studies.

INTRODUCTION: Nuclear Magnetic Resonance (NMR) spectroscopy stands as a preeminent analytical tool in the field of metabolomics. Nevertheless, when it comes to identifying metabolites present in scant amounts within various types of complex mixtures such as plants, honey, milk, and biological fluids and tissues, NMR-based metabolomics presents a formidable challenge. This predicament arises primarily from the fact that the signals emanating from metabolites existing in low concentrations tend to be overshadowed by the signals of highly concentrated metabolites within NMR spectra. OBJECTIVES: The aim of this study is to tackle the issue of intense sugar signals overshadowing the desired metabolite signals, an optimal pulse sequence with band-selective excitation has been proposed for the suppression of sugar's moiety signals (SSMS). This sequence serves the crucial purpose of suppressing unwanted signals, with a particular emphasis on mitigating the interference caused by sugar moieties' signals. METHODS: We have implemented this comprehensive approach to various NMR techniques, including 1D 1H presaturation (presat), 2D J-resolved (RES), 2D 1H-1H Total Correlation Spectroscopy (TOCSY), and 2D 1H-13C Heteronuclear Single Quantum Coherence (HSQC) for the samples of dates-flesh, honey, a standard stock solution of glucose, and nine amino acids, and commercial fetal bovine serum (FBS). RESULTS: The outcomes of this approach were significant. The suppression of the high-intensity sugar signals has considerably enhanced the visibility and sensitivity of the signals emanating from the desired metabolites. CONCLUSION: This, in turn, enables the identification of a greater number of metabolites. Additionally, it streamlines the experimental process, reducing the time required for the comparative quantification of metabolites in statistical studies in the field of metabolomics.

Unveiling the interplay between NSAID-induced dysbiosis and autoimmune liver disease in children: insights into the hidden gateway to autism spectrum disorders. Evidence from ex vivo, in vivo, and clinical studies.

Autism spectrum disorders (ASD) represent a diverse group of neuropsychiatric conditions, and recent evidence has suggested a connection between ASD and microbial dysbiosis. Immune and gastrointestinal dysfunction are associated with dysbiosis, and there are indications that modulating the microbiota could improve ASD-related behaviors. Additionally, recent findings highlighted the significant impact of microbiota on the development of autoimmune liver diseases, and the occurrence of autoimmune liver disease in children with ASD is noteworthy. In the present study, we conducted both an in vivo study and a clinical study to explore the relationship between indomethacin-induced dysbiosis, autoimmune hepatitis (AIH), and the development of ASD. Our results revealed that indomethacin administration induced intestinal dysbiosis and bacterial translocation, confirmed by microbiological analysis showing positive bacterial translocation in blood cultures. Furthermore, indomethacin administration led to disturbed intestinal permeability, evidenced by the activation of the NLRP3 inflammasomes pathway and elevation of downstream biomarkers (TLR4, IL18, caspase 1). The histological analysis supported these findings, showing widened intestinal tight junctions, decreased mucosal thickness, inflammatory cell infiltrates, and collagen deposition. Additionally, the disturbance of intestinal permeability was associated with immune activation in liver tissue and the development of AIH, as indicated by altered liver function, elevated ASMA and ANA in serum, and histological markers of autoimmune hepatitis. These results indicate that NSAID-induced intestinal dysbiosis and AIH are robust triggers for ASD existence. These findings were further confirmed by conducting a clinical study that involved children with ASD, autoimmune hepatitis (AIH), and a history of NSAID intake. Children exposed to NSAIDs in early life and complicated by dysbiosis and AIH exhibited elevated serum levels of NLRP3, IL18, liver enzymes, ASMA, ANA, JAK1, and IL6. Further, the correlation analysis demonstrated a positive relationship between the measured parameters and the severity of ASD. Our findings suggest a potential link between NSAIDs, dysbiosis-induced AIH, and the development of ASD. The identified markers hold promise as indicators for early diagnosis and prognosis of ASD. This research highlights the importance of maintaining healthy gut microbiota and supports the necessity for further investigation into the role of dysbiosis and AIH in the etiology of ASD.

The Dsup coordinates grain development and abiotic stress in rice.

DNA damage is a serious threat to all living organisms and may be induced by environmental stressors. Previous studies have revealed that the tardigrade (Ramazzotius varieornatus) DNA damage suppressor protein Dsup has protective effects in human cells and tobacco. However, whether Dsup provides radiation damage protection more widely in crops is unclear. To explore the effects of Dsup in other crops, stable Dsup overexpression lines through Agrobacterium-mediated transformation were generated and their agronomic traits were deeply investigated. In this study, the overexpression of Dsup not only enhanced the DNA damage resistance at the seeds and seedlings stages, they also exhibited grain size enlargement and starch granule structure and cell size alteration by the scanning electron microscopy observation. Notably, the RNA-seq revealed that the Dsup plants increased radiation-related and abiotic stress-related gene expression in comparison to wild types, suggesting that Dsup is capable to coordinate normal growth and abiotic stress resistance in rice. Immunoprecipitation enrichment with liquid chromatography-tandem mass spectrometry (IP-LC-MS) assays uncovered 21 proteins preferably interacting with Dsup in plants, suggesting that Dsup binds to transcription and translation related proteins to regulate the homeostasis between DNA protection and plant development. In conclusion, our data provide a detailed agronomic analysis of Dsup plants and potential mechanisms of Dsup function in crops. Our findings provide novel insights for the breeding of crop radiation resistance.

Synthesis of novel pyrazolone candidates with studying some biological activities and in-silico studies.

Pyranopyrazole derivatives have a vital role in the class of organic compounds because of their broad spectrum of biological and pharmacological importance. Our current goal is the [3 + 3] cycloaddition of benzoyl isothiocyanate and pyrazolone 1 to undergo oxidation cyclization, producing pyrazoloxadiazine 3. The diol 5 was obtained as a condensation of two equivalents of 1 with thiophene-2-carboxaldehyde in acetic acid above the sodium acetate mixture. When the condensation was carried out in piperidine under fusion, unsaturated ketone 4 was obtained. The pyrazolo pyran derivative 11 resulted from the [3 + 3] cycloaddition of 1 and cinnamic acid, while the Pyrone derivative was prepared by acylation of 12 with two equivalents of acetic anhydride. Phthalic anhydride undergoes arylation using zinc chloride as a catalyst. The cyclic keto acid 23 was synthesized by the action of succinic anhydride on 12 in the acetic medium, while the latter reacted with cinnamic acid, leading to pyrazole derivative 24. All of these reactions were through the Michael reaction mechanism. All the tested compounds showed good antimicrobial activity against pathogenic microorganisms; newly synthesized compounds were also screened for their antioxidant activity. Rational studies were carried out by the ABTs method to allow a broader choice of activities. In addition, similar off-compounds were conducted. Molecular docking studies with the CB-Dock server and MD simulations were created with the default settings of the Solution Builder on the CHARMM-GUI server at 150 nm. A good correlation was obtained between the experimental results and the theoretical bioavailability predictions using POM theory.