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.

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.

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.

Atomically Dispersed Fe-Cu Dual-Metal Sites Synergistically Boost Carbonylation of Methane.

The production of acetic acid, an important industrial chemical traditionally obtained through the carbonylation of methanol using noble metal-based homogeneous catalysts, encounters challenges arising from high equipment costs and sustainability concerns. The direct liquid-phase oxidative carbonylation of methane emerges as a promising alternative, capitalizing on abundant natural gas resources and featuring a potentially mild and straightforward process. However, most catalysts proposed for this process suffer from low acetic acid yields due to the scarcity of active sites and the swift generation of C1 oxygenates, posing difficulties for subsequent carbonylation and impeding their industrial feasibility. Herein, we report a highly efficient 0.1Cu/Fe-HZ5-TF catalyst featuring exclusively mononuclear Fe and Cu anchored in the ZSM-5 channels. Under optimized conditions, the catalyst achieved an unprecedented acetic acid yield of 40.5 mmol gcat-1 h-1 at 50 °C, surpassing the previous maximum (12.0 mmol gcat-1h-1) by more than threefold. Comprehensive characterization, isotope-labeled experiments and DFT calculations reveal that the homogeneous mononuclear Fe sites are responsible for the activation and oxidation of methane, while the neighboring Cu sites play a key role in retarding the oxidation process. This synergistic action promotes C-C coupling, resulting in the efficient synthesis of acetic acid.

Maximizing Active Fe Species in ZSM-5 Zeolite Using Organic-Template-Free Synthesis for Efficient Selective Methane Oxidation.

The selective oxidation of CH4 in the aqueous phase to produce valuable chemicals has attracted considerable attention due to its mild reaction conditions and simple process. As the most widely studied catalyst for this reaction, Fe-ZSM-5 demonstrates high intrinsic activity and selectivity; however, Fe-ZSM-5 prepared using conventional methods has a limited number of active Fe sites, resulting in low CH4 conversion per unit mass of the catalyst. This study reports a facile organic-template-free synthesis strategy that enables the incorporation of more Fe into the zeolite framework with a higher dispersion degree compared to conventional synthesis methods. Because framework Fe incorporated in this way is more readily transformed into isolated extra-framework Fe species under thermal treatment, the overall effect is that Fe-ZSM-5 prepared using this method (Fe-HZ5-TF) has 3 times as many catalytically active sites as conventional Fe-ZSM-5. When used for the selective oxidation of CH4 with 0.5 M H2O2 at 75 °C, Fe-HZ5-TF produced a high C1 oxygenate yield of 109.4 mmol gcat-1 h-1 (a HCOOH selectivity of 91.1%), surpassing other catalysts reported to date. Spectroscopic characterization and density functional theory calculations revealed that the active sites in Fe-HZ5-TF are mononuclear Fe species in the form of [(H2O)3Fe(IV)═O]2+ bound to Al pairs in the zeolite framework. This differs from conventional Fe-ZSM-5, where binuclear Fe acts as the active site. Analysis of the catalyst and product evolution during the reaction suggests a radical-driven pathway to explain CH4 activation at the mononuclear Fe site and subsequent conversion to C1 oxygenates.

A Tailored COF for Visible-Light Photosynthesis of 2,3-Dihydrobenzofurans.

Heterogeneous photocatalysis is considered as an ecofriendly and sustainable approach for addressing energy and environmental persisting issues. Recently, heterogeneous photocatalysts based on covalent organic frameworks (COFs) have gained considerable attention due to their remarkable performance and recyclability in photocatalytic organic transformations, offering a prospective alternative to homogeneous photocatalysts based on precious metal/organic dyes. Herein, we report Hex-Aza-COF-3 as a metal-free, visible-light-activated, and reusable heterogeneous photocatalyst for the synthesis of 2,3-dihydrobenzofurans, as a pharmaceutically relevant structural motif, via the selective oxidative [3+2] cycloaddition of phenols with olefins. Moreover, we demonstrate the synthesis of natural products (±)-conocarpan and (±)-pterocarpin via the [3+2] cycloaddition reaction as an important step using Hex-Aza-COF-3 as a heterogeneous photocatalyst. Interestingly, the presence of phenazine and hexaazatriphenylene as rigid heterocyclic units in Hex-Aza-COF-3 strengthens the covalent linkages, enhances the absorption in the visible region, and narrows the energy band, leading to excellent activity, charge transport, stability, and recyclability in photocatalytic reactions, as evident from theoretical calculations and real-time information on ultrafast spectroscopic measurements.

One-Pot Colloidal Synthesis Enables Highly Tunable InSb Short-Wave Infrared Quantum Dots Exhibiting Carrier Multiplication.

Colloidal quantum dots (CQDs) are emerging materials for short-wave infrared (SWIR, ≈1100-3000 nm) photodetectors, which are technologically important for a broad array of applications. Unfortunately, the most developed SWIR CQD systems are Pb and Hg chalcogenides; their toxicity and regulated compositions limit their applications. InSb CQD system is a potential environmentally friendly alternative, whose bandgap in theory, is tunable via quantum confinement across the SWIR spectrum. However, InSb CQDs are difficult to exploit, due to their complex syntheses and uncommon reactive precursors, which greatly hinder their application and study. Here, a one-pot synthesis strategy is reported using commercially available precursors to synthesize-under standard colloidal synthesis conditions-high-quality, size-tunable InSb CQDs. With this strategy, the large Bohr exciton radius of InSb can be exploited for tuning the bandgap of the CQDs over a wide range of wavelengths (≈1250-1860 nm) across the SWIR region. Furthermore, by changing the surface ligands of the CQDs from oleic acid (OA) to 1-dodecanthiol (DDT), a ≈20-fold lengthening in the excited-state lifetime, efficient carrier multiplication, and slower carrier annihilation are observed. The work opens a wide range of SWIR applications to a promising class of Pb- and Hg-free CQDs.

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.

Selectively Positioned Catechol Moiety Supports Ultrashort Self-Assembling Peptide Hydrogel Adhesion for Coral Restoration.

Coral reef survival is threatened globally. One way to restore this delicate ecosystem is to enhance coral growth by the controlled propagation of coral fragments. To be sustainable, this technique requires the use of biocompatible underwater adhesives. Hydrogels based on rationally designed ultrashort self-assembling peptides (USP) are of great interest for various biological and environmental applications, due to their biocompatibility and tunable mechanical properties. Implementing superior adhesion properties to the USP hydrogel compounds is crucial in both water and high ionic strength solutions and is relevant in medical and marine environmental applications such as coral regeneration. Some marine animals secrete large quantities of the aminoacids dopa and lysine to enhance their adhesion to wet surfaces. Therefore, the addition of catechol moieties to the USP sequence containing lysine (IIZK) should improve the adhesive properties of USP hydrogels. However, it is challenging to place the catechol moiety (Do) within the USP sequence at an optimal position without compromising the hydrogel self-assembly process and mechanical properties. Here, we demonstrate that, among three USP hydrogels, DoIIZK is the least adhesive and that the adhesiveness of the IIZDoK hydrogel is compromised by its poor mechanical properties. The best adhesion outcome was achieved using the IIZKDo hydrogel, the only one to show equally sound adhesive and mechanical properties. A mechanistic understanding of this outcome is presented here. This property was confirmed by the successful gluing of coral fragments by means of IIZKDo hydrogel that are still thriving after more than three years since the deployment. The validated biocompatibility of this underwater hydrogel glue suggests that it could be advantageously implemented for other applications, such as surgical interventions.

Salt-Tolerant Plants, Halophytes, as Renewable Natural Resources for Cancer Prevention and Treatment: Roles of Phenolics and Flavonoids in Immunomodulation and Suppression of Oxidative Stress towards Cancer Management.

Halophytes and xerophytes, plants with adequate tolerance to high salinity with strong ability to survive in drought ecosystem, have been recognized for their nutritional and medicinal values owing to their comparatively higher productions of secondary metabolites, primarily the phenolics, and the flavonoids, as compared to the normal vegetation in other climatic regions. Given the consistent increases in desertification around the world, which are associated with increasing salinity, high temperature, and water scarcity, the survival of halophytes due to their secondary metabolic contents has prioritized these plant species, which have now become increasingly important for environmental protection, land reclamation, and food and animal-feed security, with their primary utility in traditional societies as sources of drugs. On the medicinal herbs front, because the fight against cancer is still ongoing, there is an urgent need for development of more efficient, safe, and novel chemotherapeutic agents, than those currently available. The current review describes these plants and their secondary-metabolite-based chemical products as promising candidates for developing newer cancer therapeutics. It further discusses the prophylactic roles of these plants, and their constituents in prevention and management of cancers, through an exploration of their phytochemical and pharmacological properties, with a view on immunomodulation. The important roles of various phenolics and structurally diverse flavonoids as major constituents of the halophytes in suppressing oxidative stress, immunomodulation, and anti-cancer effects are the subject matter of this review and these aspects are outlined in details.

Investigating the Biological Potency of Nitazoxanide-Based Cu(II), Ni(II) and Zn(II) Complexes Synthesis, Characterization and Anti-COVID-19, Antioxidant, Antibacterial and Anticancer Activities.

In this work, the biological potency of nitazoxanide (NTZ) was enhanced through coordination with transition metal ions Cu(II), Ni(II), and Zn(II). Initially, complexes with a ligand-metal stoichiometry of 2:1 were successfully synthesized and characterized by spectroscopic techniques and thermogravimetric methods. Measurement of the infrared spectrum revealed the bidentate nature of the ligand and excluded the possibility of the metal ion-amide group interaction. Nuclear magnetic resonance spectra showed a reduction in the NH- intensity signal and integration, indicating the possibility of enolization and the formation of keto-enol tautomers. To interpret these results, density functional theory was utilized under B3LYP/6-311G** for the free ligand and B3LYP/LANL2DZ for the metal complexes. We used UV-Vis and fluorescence spectroscopy to understand the biological properties of the complexes. This showed stronger interactions of NTZ-Cu(II) and NTZ-Ni(II) with DNA molecules than the NTZ-Zn(II) compound, with a binding constant (Kb) for the copper complex of 7.00 × 105 M-1. Both Cu(II)- and Ni(II)-NTZ had functional binding to the SARS-CoV-2 (6LU7) protease. Moreover, all metal complexes showed better antioxidation properties than the free ligand, with NTZ-Ni(II) having the best IC50 value of 53.45 µg/mL. NTZ-Ni(II) was an effective antibacterial, with a mean inhibitory concentration of 6 µM, which is close to that of ampicillin (a reference drug). The metal complexes had moderated anticancer potencies, with NTZ-Cu(II) having IC50 values of 24.5 and 21.5 against human breast cancer cells (MCF-7) and cancerous cervical tumor cells (HeLa), respectively. All obtained complexes exhibited high selectivity. Finally, the metal ions showed a practical role in improving the biological effectiveness of NTZ molecules.

Bismuth Oxide Composite-Based Agricultural Waste for Wound Dressing Applications.

The purpose of this study was to enhance the antimicrobial activity of bagasse paper by coating the paper with bismuth oxide (Bi2O3) and using it to accelerate the process of wound healing. Paper sheets were prepared from sugarcane waste (bagasse). First, the paper sheets were coated with different Bi2O3 concentrations to improve the antimicrobial activity of the paper. After that, the paper sheets were allowed to dry in an oven at 50 °C for 3 h. Then, in vitro antimicrobial activity was evaluated against different microbial species, including Gram-negative bacteria (i.e., Klebsiella pneumonia, Escherichia coli) and Gram-positive bacteria (i.e., Staphylococcus aureus, Streptococcus pyogenes). The obtained results showed that the paper coated with 25% and 100% Bi2O3 had activity against all models of bacteria; however, the paper coated with 100% Bi2O3 composite had the strongest inhibitory effect. Then, bagasse paper was coated with 100% Bi2O3 and different antibiotics, to investigate their wound-healing potency in a wounded rat model for 14 days. Moreover, the paper coated with 100% Bi2O3 inhibited the cellular migration in vitro. Conclusively, coating paper with Bi2O3 enhances the wound-healing potential when applied to wounds. This impact could be ascribed to Bi2O3's broad antibacterial activity, which reduced infection and accelerated the healing process.

Exploring Nanocarriers as Treatment Modalities for Skin Cancer.

Cancer is a progressive disease of multi-factorial origin that has risen worldwide, probably due to changes in lifestyle, food intake, and environmental changes as some of the reasons. Skin cancer can be classified into melanomas from melanocytes and nonmelanoma skin cancer (NMSC) from the epidermally-derived cell. Together it constitutes about 95% of skin cancer. Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC) are creditworthy of 99% of NMSC due to the limited accessibility of conventional formulations in skin cancer cells of having multiple obstacles in treatment reply to this therapeutic regime. Despite this, it often encounters erratic bioavailability and absorption to the target. Nanoparticles developed through nanotechnology platforms could be the better topical skin cancer therapy option. To improve the topical delivery, the nano-sized delivery system is appropriate as it fuses with the cutaneous layer and fluidized membrane; thus, the deeper penetration of therapeutics could be possible to reach the target spot. This review briefly outlooks the various nanoparticle preparations, i.e., liposomes, niosomes, ethosomes, transferosomes, transethosomes, nanoemulsions, and nanoparticles technologies tested into skin cancer and impede their progress tend to concentrate in the skin layers. Nanocarriers have proved that they can considerably boost medication bioavailability, lowering the frequency of dosage and reducing the toxicity associated with high doses of the medication.

Preferential Pyrolysis Construction of Carbon Anodes with 8400†h Lifespan for High-Energy-Density K-ion Batteries.

Carbonaceous materials are promising anodes for practical potassium-ion batteries, but fail to meet the requirements for durability and high capacities at low potentials. Herein, we constructed a durable carbon anode for high-energy-density K-ion full cells by a preferential pyrolysis strategy. Utilizing S and N volatilization from a π-π stacked supermolecule, the preferential pyrolysis process introduces low-potential active sites of sp2 hybridized carbon and carbon vacancies, endowing a low-potential "vacancy-adsorption/intercalation" mechanism. The as-prepared carbon anode exhibits a high capacity of 384.2 mAh g-1 (90 % capacity locates below 1 V vs. K/K+ ), which contributes to a high energy density of 163 Wh kg-1 of K-ion full battery. Moreover, abundant vacancies of carbon alleviate volume variation, boosting the cycling stability over 14 000 cycles (8400 h). Our work provides a new synthesis approach for durable carbon anodes of K-ion full cells with high energy densities.

Co-Solvent Electrolyte Engineering for Stable Anode-Free Zinc Metal Batteries.

Anode-free metal batteries can in principle offer higher energy density, but this requires them to have extraordinary Coulombic efficiency (>99.7%). Although Zn-based metal batteries are promising for stationary storage, the parasitic side reactions make anode-free batteries difficult to achieve in practice. In this work, a salting-in-effect-induced hybrid electrolyte is proposed as an effective strategy that enables both a highly reversible Zn anode and good stability and compatibility toward various cathodes. The as-prepared electrolyte can also work well under a wide temperature range (i.e., from -20 to 50 °C). It is demonstrated that in the presence of propylene carbonate, triflate anions are involved in the Zn2+ solvation sheath structure, even at a low salt concentration (2.14 M). The unique solvation structure results in the reduction of anions, thus forming a hydrophobic solid electrolyte interphase. The waterproof interphase along with the decreased water activity in the hybrid electrolyte effectively prevents side reactions, thus ensuring a stable Zn anode with an unprecedented Coulombic efficiency (99.93% over 500 cycles at 1 mA cm-2). More importantly, we design an anode-free Zn metal battery that exhibits excellent cycling stability (80% capacity retention after 275 cycles at 0.5 mA cm-2). This work provides a universal strategy to design co-solvent electrolytes for anode-free Zn metal batteries.

Lecithin Capping Ligands Enable Ultrastable Perovskite-Phase CsPbI3 Quantum Dots for Rec. 2020 Bright-Red Light-Emitting Diodes.

Bright-red light-emitting diodes (LEDs) with a narrow emission line width that emit between 620 and 635 nm are needed to meet the latest industry color standard for wide color gamut displays, Rec. 2020. CsPbI3 perovskite quantum dots (QDs) are one of the few known materials that are ideally suited to meet these criteria. Unfortunately, CsPbI3 perovskite QDs are prone to transform into a non-red-emitting phase and are subject to further degradation mechanisms when their luminescence wavelength is tuned to match that of the Rec. 2020 standard. Here, we show that zwitterionic lecithin ligands can stabilize the perovskite phase of CsPbI3 QDs for long periods in air for at least 6 months compared to a few days for control samples. LEDs fabricated with our ultrastable lecithin-capped CsPbI3 QDs exhibit an external quantum efficiency (EQE) of 7.1% for electroluminescence centered at 634 nm─a record for all-inorganic perovskite nanocrystals in Rec. 2020 red. Our devices achieve a maximum luminance of 1391 cd/m2 at 7.5 V, and their operational half-life is 33 min (T50) at 200 cd/m2─a 10-fold enhancement compared to control samples. Density functional theory results suggest that the surface strain in CsPbI3 QDs capped with the conventional ligands, oleic acid and oleylamine, contributes to the instability of the perovskite structural phase. On the other hand, lecithin binding induces virtually no surface strain and shows a stronger binding tendency for the CsPbI3 surface. Our study highlights the tremendous potential of zwitterionic ligands in stabilizing the perovskite phase and particle size of CsPbI3 QDs for various optoelectronic applications.

Host-dependent nitrogen recycling as a mechanism of symbiont control in Aiptasia.

The metabolic symbiosis with photosynthetic algae allows corals to thrive in the oligotrophic environments of tropical seas. Different aspects of this relationship have been investigated using the emerging model organism Aiptasia. However, many fundamental questions, such as the nature of the symbiotic relationship and the interactions of nutrients between the partners remain highly debated. Using a meta-analysis approach, we identified a core set of 731 high-confidence symbiosis-associated genes that revealed host-dependent recycling of waste ammonium and amino acid synthesis as central processes in this relationship. Subsequent validation via metabolomic analyses confirmed that symbiont-derived carbon enables host recycling of ammonium into nonessential amino acids. We propose that this provides a regulatory mechanism to control symbiont growth through a carbon-dependent negative feedback of nitrogen availability to the symbiont. The dependence of this mechanism on symbiont-derived carbon highlights the susceptibility of this symbiosis to changes in carbon translocation, as imposed by environmental stress.

Ultrashort Peptide Bioinks Support Automated Printing of Large-Scale Constructs Assuring Long-Term Survival of Printed Tissue Constructs.

We report about rationally designed ultrashort peptide bioinks, overcoming severe limitations in current bioprinting procedures. Bioprinting is increasingly relevant in tissue engineering, regenerative and personalized medicine due to its ability to fabricate complex tissue scaffolds through an automated deposition process. Printing stable large-scale constructs with high shape fidelity and enabling long-term cell survival are major challenges that most existing bioinks are unable to solve. Additionally, they require chemical or UV-cross-linking for the structure-solidifying process which compromises the encapsulated cells, resulting in restricted structure complexity and low cell viability. Using ultrashort peptide bioinks as ideal bodylike but synthetic material, we demonstrate an instant solidifying cell-embedding printing process via a sophisticated extrusion procedure under true physiological conditions and at cost-effective low bioink concentrations. Our printed large-scale cell constructs and the chondrogenic differentiation of printed mesenchymal stem cells point to the strong potential of the peptide bioinks for automated complex tissue fabrication.

Thymosin ß4 Is an Endogenous Iron Chelator and Molecular Switcher of Ferroptosis.

Thymosin ß4 (Tß4) was extracted forty years agofrom calf thymus. Since then, it has been identified as a G-actin binding protein involved in blood clotting, tissue regeneration, angiogenesis, and anti-inflammatory processes. Tß4 has also been implicated in tumor metastasis and neurodegeneration. However, the precise roles and mechanism(s) of action of Tß4 in these processes remain largely unknown, with the binding of the G-actin protein being insufficient to explain these multi-actions. Here we identify for the first time the important role of Tß4 mechanism in ferroptosis, an iron-dependent form of cell death, which leads to neurodegeneration and somehow protects cancer cells against cell death. Specifically, we demonstrate four iron2+ and iron3+ binding regions along the peptide and show that the presence of Tß4 in cell growing medium inhibits erastin and glutamate-induced ferroptosis in the macrophage cell line. Moreover, Tß4 increases the expression of oxidative stress-related genes, namely BAX, hem oxygenase-1, heat shock protein 70 and thioredoxin reductase 1, which are downregulated during ferroptosis. We state the hypothesis that Tß4 is an endogenous iron chelator and take part in iron homeostasis in the ferroptosis process. We discuss the literature data of parallel involvement of Tß4 and ferroptosis in different human pathologies, mainly cancer and neurodegeneration. Our findings confronted with literature data show that controlled Tß4 release could command on/off switching of ferroptosis and may provide novel therapeutic opportunities in cancer and tissue degeneration pathologies.

Extraction and Fractionation of Prokinetic Phytochemicals from Chrozophora tinctoria and Their Bioactivities.

Chrozophora tinctoria is an annual plant of the family Euphorbiaceae, traditionally used as a laxative, a cathartic and an emetic. A methanolic extract of Chrozophora tinctoria (MEC) whole plant and an n-butanol fraction of Chrozophora tinctoria (NBFC) were analyzed by gas chromatography-mass spectrometry (GC-MS) to detect the phytochemicals. MEC and NBFC were tested for in vitro anti acetylcholinesterase (AChE) potential. The effect of both samples on intestinal propulsive movement and spasmolytic activity in the gastrointestinal tract (GIT) was also studied. About twelve compounds in MEC and three compounds in NBFC were tentatively identified through GC-MS. Some of them are compounds with known therapeutic activity, such as toluene; imipramine; undecane; 14-methyl-pentadecanoic acid methyl ester; and hexadecanoic acid. Both NBFC and MEC samples were checked for acute toxicity and were found to be highly toxic in a dose-dependent manner, causing diarrhea and emesis at 1 g/kg concentration in pigeons, with the highest lethargy and mortality above 3 g/kg. Both the samples of Chrozophora tinctoria revealed significant (p ≤ 0.01) laxative activity against metronidazole (7 mg/kg) and loperamide hydrochloride (4 mg/kg)-induced constipation. NBFC (81.18 ± 2.5%) and MEC (68.28 ± 2.4%) significantly increased charcoal meal intestinal transit compared to distal water (41.15 ± 4.3%). NBFC exhibited a significant relaxant effect (EC50 = 3.40 ± 0.20 mg/mL) in spontaneous rabbit jejunum as compared to MEC (EC50 = 4.34 ± 0.68 mg/kg). Similarly, the impact of NBFC on KCl-induced contraction was more significant than that of MEC (EC50 values of 7.22 ± 0.06 mg/mL and 7.47 ± 0.57 mg/mL, respectively). The present study scientifically validates the folk use of Chrozophora tinctoria in the management of gastrointestinal diseases such as constipation. Further work is needed to isolate the phytochemicals that act as diarrheal agents in Chrozophora tinctoria.