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Stochastic chemical kinetics is a widely used formalism for studying stochasticity of chemical reactions inside single cells. Experimental studies of reaction networks are generally performed with cells that are part of a growing population, yet the population context is rarely taken into account when models are developed. Models that neglect the population context lose their validity whenever the studied system influences traits of cells that can be selected in the population, a property that naturally arises in the complex interplay between single-cell and population dynamics of cell fate decision systems. Here, we represent such systems as absorbing continuous-time Markov chains. We show that conditioning on non-absorption allows one to derive a modified master equation that tracks the time evolution of the expected population composition within a growing population. This allows us to derive consistent population dynamics models from a specification of the single-cell process. We use this approach to classify cell fate decision systems into two types that lead to different characteristic phases in emerging population dynamics. Subsequently, we deploy the gained insights to experimentally study a recurrent problem in biology: how to link plasmid copy number fluctuations and plasmid loss events inside single cells to growth of cell populations in dynamically changing environments. [ABSTRACT FROM AUTHOR]

Background: Tissue stimulations greatly affect cell growth, phenotype, and function, and they play an important role in modeling tissue physiology. With the goal of understanding the cellular mechanisms underlying the response of tissues to external stimulations, in vitro models of tissue stimulation have been developed in hopes of recapitulating in vivo tissue function. Methods: Herein we review the efforts to create and validate tissue stimulators responsive to electrical or mechanical stimulation including tensile, compression, torsion, and shear. Results: Engineered tissue platforms have been designed to allow tissues to be subjected to selected types of mechanical stimulation from simple uniaxial to humanoid robotic stain through equal‐biaxial strain. Similarly, electrical stimulators have been developed to apply selected electrical signal shapes, amplitudes, and load cycles to tissues, lending to usage in stem cell‐derived tissue development, tissue maturation, and tissue functional regeneration. Some stimulators also allow for the observation of tissue morphology in real‐time while cells undergo stimulation. Discussion on the challenges and limitations of tissue simulator development is provided. Conclusions: Despite advances in the development of useful tissue stimulators, opportunities for improvement remain to better reproduce physiological functions by accounting for complex loading cycles, electrical and mechanical induction coupled with biological stimuli, and changes in strain affected by applied inputs. [ABSTRACT FROM AUTHOR]

BACKGROUND: In the perpetual struggle to manage mosquito populations, there has been increasing demand for the development of biopesticides to supplant/complement current products. The insecticidal potential of Xenorhabdus and Photorhabdus has long been recognized and is of interest for the control of important mosquitoes like Aedes albopictus which vectors over 20 different arboviruses of global public health concern. RESULTS: The larvicidal effects of cell‐free supernatants, cell growth cultures and cell mass of an extensive list of Xenorhabdus and Photorhabdus spp. was investigated. They were quite effective against Ae. albopictus causing larval mortality ranging between 52–100%. Three Photorhabdus spp. and 13 Xenorhabdus spp. release larvicidal compounds in cell‐free supernatants. Cell growth culture of all tested species exhibited larvicidal activity, except for Xenorhabdus sp. TS4. Twenty‐one Xenorhabdus and Photorhabdus bacterial cells (pellet) exhibited oral toxicity (59–91%) against exposed larvae. The effect of bacterial supernatants on the mosquito eggs were also assessed. Bacterial supernatants inhibited the hatching of mosquito eggs; when unhatched eggs were transferred to clean water, they all hatched. Using the easyPACId approach, the larvicidal compounds in bacterial supernatant were identified as fabclavine from X. szentirmaii and xencoumacin from X. nematophila (causing 98 and 70% mortality, respectively, after 48 h). Xenorhabdus cabanillasii and X. hominickii fabclavines were as effective as commercial Bacillus thuringiensis subsp. israelensis and spinosad products within 5 days post‐application (dpa). CONCLUSION: Fabclavine and xenocoumacin can be developed into novel biolarvicides, can be used as a model to synthesize other compounds or/and can be combined with other commercial biolarvicides. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a promising cancer treatment. This study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[-diethylene triamine pentaacetic acid-aminophenyl]-10,15,20-triphenyl-porphyrin (DTP) mediated PDT (DTP-PDT). Cell viability, reactive oxygen species (ROS), and apoptosis were measured with a Cell Counting Kit-8 assay, DCFH-DA fluorescent probe, and Hoechst staining, respectively. Cell apoptosis- and autophagy-related proteins were examined using western blotting. RNA sequencing was used to screen differentially expressed mRNAs (DERs), and bioinformatic analysis was performed to identify the major biological events after DTP-PDT. Our results show that DTP-PDT inhibited cell growth and induced ROS generation in MCF-7 and SGC7901 cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and the P38 MAPK inhibitor SB203580 alleviated DTP-PDT-induced cytotoxicity. DTP-PDT induced cell apoptosis together with upregulated Bax and downregulated Bcl-2, which could also be inhibited by NAC or SB203580. The level of LC3B-II, a marker of autophagy, was increased by DTP-PDT. A total of 3496 DERs were obtained after DTP-PDT. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DERs included those involved in cytosolic ribosomes, the nuclear lumen, protein binding, cell cycle, protein targeting to the endoplasmic reticulum, and ribosomal DNA replication. Disease Ontology and Reactome enrichment analyses indicated that DERs were associated with a variety of cancers and cell cycle checkpoints. Protein-protein interaction results demonstrated that cdk1 and rps27a ranked in the top 10 interacting genes. Therefore, DTP-PDT could inhibit cell growth and induce cell apoptosis and autophagy, partly through ROS and the P38 MAPK signaling pathway. Genes associated with the cell cycle, ribosomes, DNA replication, and protein binding may be the key changes in DTP-PDT-mediated cytotoxicity. [ABSTRACT FROM AUTHOR]

BACKGROUND: The intestine is a barrier resisting various stress responses. Intrauterine growth restriction (IUGR) can cause damage to the intestinal barrier via destroying the balance of intestinal epithelial cells' proliferation and apoptosis. Bacillus subtilis has been reported to regulate intestinal epithelial cells' proliferation and apoptosis. Thus, the purpose of this study was to determine if B. subtilis could regulate intestinal epithelial cells' proliferation and apoptosis in intrauterine growth restriction suckling piglets. RESULTS: Compared with the normal birth weight group, the IUGR group showed greater mean optical density values of Ki‐67‐positive cells in the ileal crypt (P < 0.05). IUGR resulted in higher ability of proliferation and apoptosis of intestinal epithelial cells, by upregulation of the messenger RNA (mRNA) or proteins expression of leucine rich repeat containing G protein coupled receptor 5, Caspase‐3, Caspase‐7, β‐catenin, cyclinD1, B‐cell lymphoma‐2 associated agonist of cell death, and BCL2 associated X (P < 0.05), and downregulation of the mRNA or protein expression of B‐cell lymphoma‐2 and B‐cell lymphoma‐2‐like 1 (P < 0.05). However, B. subtilis supplementation decreased the mRNA or proteins expression of leucine rich repeat containing G protein coupled receptor 5, SPARC related modular calcium binding 2, tumor necrosis factor receptor superfamily member 19, cyclinD1, Caspase‐7, β‐catenin, B‐cell lymphoma‐2 associated agonist of cell death, and Caspase‐3 (P < 0.05), and increased the mRNA expression of B‐cell lymphoma‐2 (P < 0.05). CONCLUSION: IUGR led to excessive apoptosis of intestinal epithelial cells, which induced compensatory proliferation. However, B. subtilis treatment prevented intestinal epithelial cells of IUGR suckling piglets from excessive apoptosis. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Ovarian cancer is an aggressive, heterogeneous disease, burdened with late diagnosis and resistance to chemotherapy. Clinical features of ovarian cancer could be explained by investigating its metabolism, and how the regulation of specific pathways links to individual phenotypes. Ovarian cancer is of particular interest for metabolic research due to its heterogeneous nature, with five distinct subtypes having been identified, each of which may display a unique metabolic signature. To elucidate metabolic differences, constraint-based modelling (CBM) represents a powerful technology, inviting the integration of 'omics' data, such as transcriptomics. However, many CBM methods have not prioritised accurate growth rate predictions, and there are very few ovarian cancer genome-scale studies. Here, a novel method for CBM has been developed, employing the genome-scale model Human1 and flux balance analysis, enabling the integration of in vitro growth rates, transcriptomics data and media conditions to predict the metabolic behaviour of cells. Using low- and high-grade ovarian cancer, subtype-specific metabolic differences have been predicted, which have been supported by publicly available CRISPR-Cas9 data from the Cancer Cell Line Encyclopaedia and an extensive literature review. Metabolic drivers of aggressive, invasive phenotypes, as well as pathways responsible for increased chemoresistance in low-grade cell lines have been suggested. Experimental gene dependency data has been used to validate areas of the pentose phosphate pathway as essential for low-grade cellular growth, highlighting potential vulnerabilities for this ovarian cancer subtype. [ABSTRACT FROM AUTHOR]

Large-scale production of cultured meat requires bulk culture medium containing growth-promoting proteins from animal serum. However, animal serum for mammalian cell culture is associated with high costs, ethical concerns, and contamination risks. Owing to its growth factor content, conditioned medium from rat liver epithelial RL34 cells can replace animal serum for myoblast proliferation. More seeded cells and longer culture periods are thought to yield higher growth factor levels, resulting in more effective muscle cell proliferation. However, RL34 cells can deplete nutrients and release harmful metabolites into the culture medium over time, potentially causing growth inhibition and apoptosis. This issue highlights the need for waste clearance during condition medium production. To address this issue, we introduced a lactate permease gene (lldP) and an l-lactate-to-pyruvate conversion enzyme gene (lldD) to generate a recombinant l-lactate-assimilating cyanobacterium Synechococcus sp. KC0110 strain. Transwell co-culture of this strain with RL34 cells exhibited a marked reduction in the levels of harmful metabolites, lactate and ammonium, while maintaining higher concentrations of glucose, pyruvate, and pyruvate-derived amino acids than those seen with RL34 cell monocultures. The co-culture medium supported myoblast proliferation without medium dilution or additional nutrients, which was attributed to the waste clearance and nutrient replenishment effects of the KC0110 strain. This culture system holds potential for the production of low-cost, and animal-free cultured meat. [ABSTRACT FROM AUTHOR]

Epothilones are one of the common prescribed anticancer drugs for solid tumors, for their exceptional binding affinity with β-tubulin microtubule, stabilizing their disassembly, causing an ultimate arrest to the cellular growth. Epothilones were initially isolated from Sornagium cellulosum, however, their extremely slow growth rate and low yield of epothilone is the challenge. So, screening for a novel fungal endophyte dwelling medicinal plants, with higher epothilone productivity and feasibility of growth manipulation was the objective. Aspergillus niger EFBL-SR OR342867, an endophyte of Latania loddegesii, has been recognized as the heady epothilone producer (140.2 μg/L). The chemical structural identity of the TLC-purified putative sample of A. niger was resolved from the HPLC, FTIR and LC–ESI–MS/MS analyses, with an identical molecular structure of the authentic epothilone B. The purified A. niger epothilone B showed a resilient activity against MCF-7 (0.022 μM), HepG-2 (0.037 μM), and HCT-116 (0.12 μM), with selectivity indices 21.8, 12.9 and 4, respectively. The purified epothilone B exhibited a potential anti-wound healing activity to HepG-2 and MCF-7 cells by ~ 54.07 and 60.0%, respectively, after 24 h, compared to the untreated cells. The purified epothilone has a significant antiproliferative effect by arresting the cellular growth of MCF-7 at G2/M phase by ~ 2.1 folds, inducing the total apoptosis by ~ 12.2 folds, normalized to the control cells. The epothilone B productivity by A. niger was optimized by the response surface methodology, with ~ 1.4 fold increments (266.9 μg/L), over the control. The epothilone productivity by A. niger was reduced by ~ 2.4 folds by 6 months storage as a slope culture at 4 °C, however, the epothilone productivity was slightly restored with ethylacetate extracts of L. loddegesii, confirming the plant-derived chemical signals that partially triggers the biosynthetic genes of A. niger epothilones. So, this is the first report emphasizing the metabolic potency of A. niger, an endophyte of L. loddegesii, to produce epothilone B, that could be a new platform for industrial production of this drug. [ABSTRACT FROM AUTHOR]

Members of the SLC25 mitochondrial carrier family link cytosolic and mitochondrial metabolism and support cellular maintenance and growth by transporting compounds across the mitochondrial inner membrane. Their monomeric or dimeric state and kinetic mechanism have been a matter of long-standing debate. It is believed by some that they exist as homodimers and transport substrates with a sequential kinetic mechanism, forming a ternary complex where both exchanged substrates are bound simultaneously. Some studies, in contrast, have provided evidence indicating that the mitochondrial ADP/ATP carrier (SLC25A4) functions as a monomer, has a single substrate binding site, and operates with a ping-pong kinetic mechanism, whereby ADP is imported before ATP is exported. Here we reanalyze the oligomeric state and kinetic properties of the human mitochondrial citrate carrier (SLC25A1), dicarboxylate carrier (SLC25A10), oxoglutarate carrier (SLC25A11), and aspartate/glutamate carrier (SLC25A13), all previously reported to be dimers with a sequential kinetic mechanism. We demonstrate that they are monomers, except for dimeric SLC25A13, and operate with a ping-pong kinetic mechanism in which the substrate import and export steps occur consecutively. These observations are consistent with a common transport mechanism, based on a functional monomer, in which a single central substrate-binding site is alternately accessible. Synopsis: The human mitochondrial oxoglutarate carrier (OGC), citrate carrier (CIC), dicarboxylate carrier (DIC) and aspartate/glutamate carrier (AGC2) of the SLC25 family were all thought to be homodimers, operating with a sequential mechanism in which the two exchanged substrates bind at the same time to the transporter. This study shows that they are monomers, except for the dimeric aspartate/glutamate carrier (AGC2), and that they import one substrate first before the other is exported. The human mitochondrial citrate, dicarboxylate and oxoglutarate carriers are structural monomers. In contrast to these carriers, the mitochondrial aspartate/glutamate carrier is a structural dimer. They all operate with a ping-pong kinetic mechanism, where one substrate is imported first, before the the counter-substrate is exported. These kinetic and structural observations are consistent with an alternating access mechanism for mitochondrial carriers using a single substrate-binding site. The oxoglutarate, citrate and dicarboxylate carriers are monomeric in contrast to the dimeric aspartate/glutamate carrier, but all operate with a ping-pong kinetic mechanism. [ABSTRACT FROM AUTHOR]

Porcine Epidemic Diarrhea Virus (PEDV) poses a significant threat to neonatal piglets, particularly due to the limited efficacy of existing vaccines and the scarcity of efficacious therapeutic drugs. Gegen Qinlian Decoction (GQD) has been employed for over two millennia in treating infectious diarrhea. Nonetheless, further scrutiny is required to improve the drug's efficacy and elucidate its underlying mechanisms of action. In this study, a modified GQD (MGQD) was developed and demonstrated its capacity to inhibit the replication of PEDV. Animal trials indicated that MGQD effectively alleviated pathological damage in immune tissues and modulated T-lymphocyte subsets. The integration of network analysis with UHPLC-MS/MS facilitated the identification of active ingredients within MGQD and elucidated the molecular mechanisms underlying its therapeutic effects against PEDV infections. In vitro studies revealed that MGQD significantly impeded PEDV proliferation in IPEC-J2 cells, promoting cellular growth via virucidal activity, inhibition of viral attachment, and disruption of viral biosynthesis. Furthermore, MGQD treatment led to increased expression levels of IFN-α, IFN-β, and IFN-λ3, while concurrently decreasing the expression of TNF-α, thereby enhancing resistance to PEDV infection in IPEC-J2 cells. In conclusion, our findings suggest that MGQD holds promise as a novel antiviral agent for the treatment of PEDV infections. [ABSTRACT FROM AUTHOR]

Leishmania species, members of the kinetoplastid parasites, cause leishmaniasis, a neglected tropical disease, in millions of people worldwide. Leishmania has a complex life cycle with multiple developmental forms, as it cycles between a sand fly vector and a mammalian host; understanding their life cycle is critical to understanding disease spread. One of the key life cycle stages is the haptomonad form, which attaches to insect tissues through its flagellum. This adhesion, conserved across kinetoplastid parasites, is implicated in having an important function within their life cycles and hence in disease transmission. Here, we discover the kinetoplastid-insect adhesion proteins (KIAPs), which localise in the attached Leishmania flagellum. Deletion of these KIAPs impairs cell adhesion in vitro and prevents Leishmania from colonising the stomodeal valve in the sand fly, without affecting cell growth. Additionally, loss of parasite adhesion in the sand fly results in reduced physiological changes to the fly, with no observable damage of the stomodeal valve and reduced midgut swelling. These results provide important insights into a comprehensive understanding of the Leishmania life cycle, which will be critical for developing transmission-blocking strategies. The function of the first proteins that mediate adhesion of Leishmania parasites to its sand fly vector are reported. Loss of these proteins stops parasite adhesion, reducing physiological changes to the fly that will likely impact transmission. [ABSTRACT FROM AUTHOR]

Constructing atom-pair engineering and improving the activity of metal single-atom nanozyme (SAzyme) is significant but challenging. Herein, we design the atom-pair engineering of Zn-SA/CNCl SAzyme by simultaneously constructing Zn-N4 sites as catalytic sites and Zn-N4Cl1 sites as catalytic regulator. The Zn-N4Cl1 catalytic regulators effectively boost the peroxidase-like activities of Zn-N4 catalytic sites, resulting in a 346-fold, 1496-fold, and 133-fold increase in the maximal reaction velocity, the catalytic constant and the catalytic efficiency, compared to Zn-SA/CN SAzyme without the Zn-N4Cl1 catalytic regulator. The Zn-SA/CNCl SAzyme with excellent peroxidase-like activity effectively inhibits tumor cell growth in vitro and in vivo. The density functional theory (DFT) calculations reveal that the Zn-N4Cl1 catalytic regulators facilitate the adsorption of *H2O2 and re-exposure of Zn-N4 catalytic sites, and thus improve the reaction rate. This work provides a rational and effective strategy for improving the peroxidase-like activity of metal SAzyme by atom-pair engineering. Designing and enhancing the performance of metal single-atom nanozymes (SAzymes) through atom-pair engineering is important yet difficult. Here the authors develop the atom-pair engineering of Zn-SA/CNCl SAzyme by concurrently creating Zn-N4 sites as catalytic sites and Zn-N4Cl1 sites as catalytic regulators. [ABSTRACT FROM AUTHOR]

When ribosome-targeting antibiotics attack actively growing bacteria, they occupy ribosomal active centers, causing the ribosomes to stall or make errors that either halt cellular growth or cause bacterial death. However, emerging research indicates that bacterial ribosomes spend a considerable amount of time in an inactive state known as ribosome hibernation, in which they dissociate from their substrates and bind to specialized proteins called ribosome hibernation factors. Since 60% of microbial biomass exists in a dormant state at any given time, these hibernation factors are likely the most common partners of ribosomes in bacterial cells. Furthermore, some hibernation factors occupy ribosomal drug-binding sites - leading to the question of how ribosome hibernation influences antibiotic efficacy, and vice versa. In this review, we summarize the current state of knowledge on physical and functional interactions between hibernation factors and ribosometargeting antibiotics and explore the possibility of using antibiotics to target not only active but also hibernating ribosomes. Because ribosome hibernation empowers bacteria to withstand harsh conditions such as starvation, stress, and host immunity, this line of research holds promise for medicine, agriculture, and biotechnology: by learning to regulate ribosome hibernation, we could enhance our capacity to manage the survival of microorganisms in dormancy. [ABSTRACT FROM AUTHOR]

Bacterial membrane vesicles (BMVs) are crucial biological vehicles for facilitating interspecies and interkingdom interactions. However, the extent and mechanisms of BMV involvement in bacterial-algal communication remain elusive. This study provides evidence of BMVs delivering cargos to targeted microalgae. Membrane vesicles (MVs) from Chitinimonas prasina LY03 demonstrated an algicidal profile similar to strain LY03. Further investigation revealed Tambjamine LY2, an effective algicidal compound, selectively packaged into LY03-MVs. Microscopic imaging demonstrated efficient delivery of Tambjamine LY2 to microalgae Heterosigma akashiwo and Thalassiosira pseudonana through membrane fusion. In addition, the study demonstrated the versatile cargo delivery capabilities of BMVs to algae, including the transfer of MV-carried nucleic acids into algal cells and the revival of growth in iron-depleted microalgae by MVs. Collectively, our findings reveal a previously unknown mechanism by which algicidal bacteria store hydrophobic algicidal compounds in MVs to trigger target microalgae death and highlight BMV potency in understanding and engineering bacterial-algae cross-talk. [ABSTRACT FROM AUTHOR]

Limiting cellular plasticity is of key importance for the therapeutic targeting of metastatic breast cancer (MBC). Fibroblast growth receptor (FGFR) is a critical molecule in cellular plasticity and potent inhibitors of FGFR enzymatic activity have been developed, but kinase independent functions for this receptor also contribute to MBC progression. Herein, we evaluated several FGFR inhibitors and find that while FGFR-targeted kinase inhibitors are effective at blocking ligand-induced cell growth, dormant cells persist eventually giving rise to MBC progression. To more broadly target FGFR and cellular plasticity, we examined the FGFR1 proximal promoter, and found several sequences with potential to form G-quadruplex secondary structures. Circular dichroism was used to verify formation of G-quadruplex in the FGFR1 proximal promoter. Importantly, use of the clinical G-quadruplex-stabilizing compound, CX-5461, stabilized the FGFR1 G-quadruplex structures, blocked the transcriptional activity of the FGFR1 proximal promoter, decreased FGFR1 expression, and resulted in potent inhibition of pulmonary tumor formation. Overall, our findings suggest G-quadruplex-targeted compounds could be a potential therapeutic strategy to limit the cellular plasticity of FGFR1 overexpressing MBC. This study demonstrates the regulation of FGFR1 expression in metastatic breast cancer through the stabilization of G-quadruplex in its proximal promoter. [ABSTRACT FROM AUTHOR]

Translation is regulated mainly in the initiation step, and its dysregulation is implicated in many human diseases. Several proteins have been found to regulate translational initiation, including Pdcd4 (programmed cell death gene 4). Pdcd4 is a tumor suppressor protein that prevents cell growth, invasion, and metastasis. It is downregulated in most tumor cells, while global translation in the cell is upregulated. To understand the mechanisms underlying translational control by Pdcd4, we used single-particle cryo-electron microscopy to determine the structure of human Pdcd4 bound to 40S small ribosomal subunit, including Pdcd4-40S and Pdcd4-40S-eIF4A-eIF3-eIF1 complexes. The structures reveal the binding site of Pdcd4 at the mRNA entry site in the 40S, where the C-terminal domain (CTD) interacts with eIF4A at the mRNA entry site, while the N-terminal domain (NTD) is inserted into the mRNA channel and decoding site. The structures, together with quantitative binding and in vitro translation assays, shed light on the critical role of the NTD for the recruitment of Pdcd4 to the ribosomal complex and suggest a model whereby Pdcd4 blocks the eIF4F-independent role of eIF4A during recruitment and scanning of the 5′ UTR of mRNA. Tumor suppressor protein Pdcd4 is downregulated in tumor cells, whereas global mRNA translation within these cells is upregulated. Here, the authors determined the structure of human Pdcd4 bound to the ribosome, revealing how it blocks translation. [ABSTRACT FROM AUTHOR]

Cells can respond and adapt to complex forms of environmental change. Budding yeast is widely used as a model system for these stress response studies. In these studies, the precise control of the environment with high temporal resolution is most important. However, there is a lack of single-cell research platforms that enable precise control of the temperature and form of cell growth. This has hindered our understanding of cellular coping strategies in the face of diverse forms of temperature change. Here, we developed a novel temperature-controlled microfluidic platform that integrates a microheater (using liquid metal) and a thermocouple (liquid metal vs. conductive PDMS) on a chip. Three forms of temperature changes (step, gradient, and periodical oscillations) were realized by automated equipment. The platform has the advantages of low cost and a simple fabrication process. Moreover, we investigated the nuclear entry and exit behaviors of the transcription factor Msn2 in yeast in response to heat stress (37 °C) with different heating modes. The feasibility of this temperature-controlled platform for studying the protein dynamic behavior of yeast cells was demonstrated. [ABSTRACT FROM AUTHOR]

Cell growth is required for cell cycle progression. The amount of growth required for cell cycle progression is reduced in poor nutrients, which leads to a reduction in cell size. In budding yeast, nutrients can influence cell size by modulating the extent of bud growth, which occurs predominantly in mitosis. However, the mechanisms are unknown. Here, we used mass spectrometry to identify proteins that modulate bud growth in response to nutrient availability. This led to the discovery that nutrients regulate numerous components of the mitotic exit network (MEN), which controls exit from mitosis. A key component of the MEN undergoes gradual multisite phosphorylation during bud growth that is dependent upon bud growth and correlated with the extent of growth. Furthermore, activation of the MEN is sufficient to override a growth requirement for mitotic exit. The data suggest a model in which the MEN ensures that mitotic exit occurs only when an appropriate amount of bud growth has occurred. [ABSTRACT FROM AUTHOR]

In order to investigate the changes in the properties of the cell culture solution in the effect of cell synchronization via cell starvation (for 12, 24, and 36 h), a new spiral-interdigital pattern of microelectrode as a biosensor has been proposed. Then, to test its superiority, the results of this spiral-interdigital pattern with the results of the commercial pattern have been compared. The cells were selected from breast cancer standard lines (MDA-MB-231). Changes in CV peaks of the secretions were recorded by the spiral-interdigital pattern, in which increasing the interactive surface with homogenous electric paths had been considered by simulation before fabrication. The results of the simulation and experimental procedures showed a meaningful correlation. The occurrence of CV oxidative peaks at about 0.1–0.4 V and reductive peaks at approximately 0 V in the spiral-interdigital biosensor in the starved MDA-MB-231 cell line has been observed. The starvation situation resembles one that does not cause meaningful cell apoptosis or necrosis, and this method is only used to make the cells synchronized. Also, no peak is observed in normal cell growth conditions. In addition, by using the commercial design of the electrodes, no peak is observed in any of the conditions of normal and synchronized growth of the cells. Therefore, it seems that the observed peaks are caused by the agents that are secreted in the cell culture solution in a synchronized situation. Moreover, the design of the new spiral-interdigital electrode can significantly increase the sensitivity of the sensor to receive these peaks due to more space and a uniform electric field. [ABSTRACT FROM AUTHOR]

Chromobox (CBX) 2, a member of the CBX protein family and a crucial component of the polycomb repressive complex (PRC), exerts significant influence on the epigenetic regulation of tumorigenesis, including glioma. However, the precise role of CBX2 in glioma has remained elusive. In our study, we observed a substantial upregulation of CBX2 expression in glioma, which displayed a strong correlation with pathological grade, chemoresistance, and unfavorable prognosis. Through a series of in vivo and in vitro experiments, we established that heightened CBX2 expression facilitated glioma cell proliferation and bolstered resistance to chemotherapy. Conversely, CBX2 knockdown led to a significant inhibition of glioma cell growth and a reduction in chemoresistance. Notably, our investigation uncovered the underlying mechanism by which CBX2 operates, primarily by inhibiting PTEN transcription and activating the AKT/mTOR signalling pathway. Conversely, silencing CBX2 curtailed cell proliferation and attenuated chemoresistance by impeding the activation of the PTEN/AKT/mTOR signalling pathway. Delving deeper into the molecular intricacies, we discovered that CBX2 can recruit EZH2 and modulate the trimethylation of histone H3 lysine 27 (H3K27me3) levels on the PTEN promoter, effectively suppressing PTEN transcription. Our research unveils a comprehensive understanding of how CBX2 impacts the tumorigenesis, progression, chemoresistance, and prognosis of glioma. Furthermore, it presents CBX2 as a promising therapeutic target for drug development and clinical management of glioma. [ABSTRACT FROM AUTHOR]

Recent advances in genetic sequencing are transforming our approach to rare-disease care. Initially identified in cancer, gain-of-function mutations of the PIK3CA gene are also detected in malformation mosaic diseases categorized as PIK3CA-related disorders (PRDs). Over the past decade, new approaches have enabled researchers to elucidate the pathophysiology of PRDs and uncover novel therapeutic options. In just a few years, owing to vigorous global research efforts, PRDs have been transformed from incurable diseases to chronic disorders accessible to targeted therapy. However, new challenges for both medical practitioners and researchers have emerged. Areas of uncertainty remain in our comprehension of PRDs, especially regarding the relationship between genotype and phenotype, the mechanisms underlying mosaicism, and the processes involved in intercellular communication. As the clinical and biological landscape of PRDs is constantly evolving, this review aims to summarize current knowledge regarding PIK3CA and its role in nonmalignant human disease, from molecular mechanisms to evidence-based treatments. [ABSTRACT FROM AUTHOR]

This study presents a short overview of the main 3D polymer composite items that are fabricated by extrusion and stereolithography printing. By coupling polymers traditionally used in additive manufacturing, such as PEGDA, and polymers of biomedical interest, such as PVA, with carbon nanostructures, such as nanodiamond and graphene nanoplates, and conductive polymers, such as PEDOT and PANI, it has been possible to produce objects with specific functional properties exploited for fabricating scaffolds for cell growth and proliferation as well as soft electrodes for developing organic compounds sensing devices and electrocardiogram monitoring systems under real‐time conditions. [ABSTRACT FROM AUTHOR]

The tumor suppressor p14/19ARF regulates ribosomal RNA (rRNA) synthesis by controlling the nucleolar localization of Transcription Termination Factor 1 (TTF1). However, the role played by TTF1 in regulating the rRNA genes and in potentially controlling growth has remained unclear. We now show that TTF1 expression regulates cell growth by determining the cellular complement of ribosomes. Unexpectedly, it achieves this by acting as a "roadblock" to synthesis of the noncoding LncRNA and pRNA that we show are generated from the "Spacer Promoter" duplications present upstream of the 47S pre‐rRNA promoter on the mouse and human ribosomal RNA genes. Unexpectedly, the endogenous generation of these noncoding RNAs does not induce CpG methylation or gene silencing. Rather, it acts in cis to suppress 47S preinitiation complex formation and hence de novo pre‐rRNA synthesis by a mechanism reminiscent of promoter interference or occlusion. Taken together, our data delineate a pathway from p19ARF to cell growth suppression via the regulation of ribosome biogenesis by noncoding RNAs and validate a key cellular growth law in mammalian cells. [ABSTRACT FROM AUTHOR]

Exosomes from cancer cells function as carriers to spread or transport specific microRNAs (miRNAs) to distant sites to exert their effects, but the mechanism of exosomal miRNA action in esophageal squamous cell carcinoma (ESCC) has not been fully explained. Therefore, in this study, we were interested in the impact of exosomal miR‐196a‐5p in ESCC progression. We found that miR‐196a‐5p was expressed enriched in clinical tissues, ESCC cells, and exosomes. Functionally, depletion of miR‐196a‐5p impeded ESCC cell growth, migration, and invasion, whereas overexpression of miR‐196a‐5p produced the opposite results. Moreover, enhancement of exosomal miR‐196a‐5p in recipient ESCC cells triggered more intense proliferation and migration. Mechanistically, we identified integral membrane protein 2B (ITM2B) as a direct target of miR‐196a‐5p. Silencing of ITM2B partially counteracted the inhibitory effect of miR‐196a‐5p inhibitors on the malignant phenotype of ESCC. Furthermore, in vivo, lower miR‐196a‐5p levels triggered by the introduction of antagomiR‐196a‐5p resulted in the generation of smaller volume and weight xenograft tumors. Thus, our results demonstrated novel mechanisms of exosomal and intracellular miR‐196a‐5p‐mediated ESCC growth and migration and identify the interaction of miR‐196a‐5p with ITM2B. These works might provide new targets and basis for the development of clinical treatment options for ESCC. [ABSTRACT FROM AUTHOR]

The anti‐cancer potential of Cyclopia species (honeybush) has been demonstrated in several models. The present study investigated the effects of aqueous and polyphenol‐enriched (PE) extracts of C. subternata and C. genistoides, as well as mangiferin and hesperidin, on different cell growth parameters in human liver (HepG2) and colon (HT‐29) cancer cells. Mangiferin and hesperidin were most abundant in C. genistoides and C. subternata, respectively. Cyclopia subternata extracts had the highest ferric‐reducing antioxidant capacity. Following exposure of the cells to the extracts and compounds, cell viability, proliferation, and death (apoptosis and autophagy) were determined. Cyclopia subternata extracts reduced cell viability and inhibited cell proliferation the most, associated with depletion of ATP. In HepG2 cells, the PE extracts were less effective than the aqueous extracts in reducing cell viability but more effective in inhibiting cell proliferation. Despite disrupting cell growth, none of the extracts induced apoptosis. The aqueous extracts affected autophagy in both cancer cells. Disruption of mitochondrial membrane integrity by the different extracts, presumably via polyphenol/iron interactions, is postulated to be involved; however, mangiferin and hesperidin had no effect, suggesting that other polyphenols and/or complex interactions between compounds are likely responsible for the differential cytotoxic and/or cytoprotective effects of the extracts. [ABSTRACT FROM AUTHOR]

Understanding the complex dynamics of telomere biology is important in the strong link between aging and cancer. Telomeres, the protective caps at the end of chromosomes, are central players in this connection. While their gradual shortening due to replication limits tumors expansion by triggering DNA repair mechanisms, it also promotes oncogenic changes within chromosomes, thus sustaining tumorigenesis. The enzyme telomerase, responsible for maintaining telomere length, emerges as a central player in this context. Its expression in cancer cells facilitates the preservation of telomeres, allowing them to circumvent the growth-limiting effects of short telomeres. Interestingly, the influence of telomerase extends beyond telomere maintenance, as evidenced by its involvement in promoting cell growth through alternative pathways. In this context, inflammation accelerates telomere shortening, resulting in telomere dysfunction, while telomere elements also play a role in modulating the inflammatory response. The recognition of this interplay has promoted the development of novel therapeutic approaches centered around telomerase inhibition. This review provides a comprehensive overview of the field, emphasizing recent progress in knowledge and the implications in understanding of cancer biology. [ABSTRACT FROM AUTHOR]

Isoamyl 4-methoxycinnamate (IMC) is widely used in various fields because of its exceptional UV-filter properties. However, due to its cytotoxicity and anti-microbial degradability, the potential eco-environmental toxicity of IMC has become a focus of attention. In this study, we propose a host–guest supramolecule approach to enhance the functionality of IMC, resulting in a more environmentally friendly and high-performance materials. Sulfobutyl-β-cyclodextrin sodium salt (SBE-β-CD) was used as the host molecule. IMC-SBE-β-CD supramolecular substances were prepared through the "saturated solution method", and their properties and biosecurity were evaluated. Meanwhile, we conducted the AOS tree evaluation system that surpasses existing evaluation approaches based on apoptosis, oxidative stress system, and signaling pathways to investigate the toxicological mechanisms of IMC-SBE-β-CD within human hepatoma SMMC-7721 cells as model organisms. The AOS tree evaluation system aims to offer the comprehensive analysis of the cytotoxic effects of IMC-SBE-β-CD. Our findings showed that IMC-SBE-β-CD had an encapsulation rate of 84.45% and optimal stability at 30 °C. Further, IMC-SBE-β-CD promoted cell growth and reproduction without compromising the integrity of mitochondria and nucleus or disrupting oxidative stress and apoptosis-related pathways. Compared to IMC, IMC-SBE-β-CD is biologically safe and has improved water solubility with the UV absorption property maintained. Our study provides the foundation for the encapsulation of hydrophobic, low-toxicity organic compounds using cyclodextrins and offers valuable insights for future research in this field. [ABSTRACT FROM AUTHOR]

Reduced nicotinamide adenine dinucleotide phosphate (NADPH) is a crucial cofactor in metabolic networks. The efficient regeneration of NADPH is one of the limiting factors for productivity in biotransformation processes. To date, many metabolic engineering tools and static regulation strategies have been developed to regulate NADPH regeneration. However, traditional static regulation methods often lead to the NADPH/NADP+ imbalance, causing disruptions in cell growth and production. These methods also fail to provide real-time monitoring of intracellular NADP(H) or NADPH/NADP+ levels. In recent years, various biosensors have been developed for the detection, monitoring, and dynamic regulate of the intracellular NADP(H) levels or the NADPH/NADP+ balance. These NADPH-related biosensors are mainly used in the cofactor engineering of bacteria, yeast, and mammalian cells. This review analyzes and summarizes the NADPH metabolic regulation strategies from both static and dynamic perspectives, highlighting current challenges and potential solutions, and discusses future directions for the advanced regulation of the NADPH/NADP+ balance. [ABSTRACT FROM AUTHOR]

Melanoma, a cancer arising from melanocytes, requires a novel treatment strategy because of the ineffectiveness of conventional therapies in certain patients. Fustin is a flavanonol found in young fustic (Cotinus coggygria). However, little is known about its antimelanoma effects. Our study demonstrates that fustin suppresses the growth of B16 melanoma cells. Phalloidin staining of cytoskeletal actin revealed that fustin induced a conformational change in the actin structure of melanoma cells, accompanied by suppressed phosphorylation of myosin regulatory light chain 2 (MLC2), a regulator of actin structure. Furthermore, the protein kinase A (cAMP-dependent protein kinase) inhibitor H89 completely attenuated fustin-induced downregulation of phosphorylated myosin phosphatase targeting subunit 1, which is involved in dephosphorylation of MLC2. In a mouse model, administration of fustin suppressed tumor growth in B16 melanoma cells without adverse effects. In conclusion, our findings suggest that fustin effectively suppresses melanoma cell growth both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

To clarify the growth mechanisms of Rhodococcus in the alkane phase, we measured oxygen utilization in the alkane phase. The results showed that dissolved oxygen decreased significantly when viable cells were present in the alkane phase. The findings suggested that Rhodococcus strains can grow in alkanes and utilize the resident dissolved oxygen. [ABSTRACT FROM AUTHOR]

In the fission yeast Schizosaccharomyces pombe, the response to sulfur depletion has been less studied compared to the response to nitrogen depletion. Our study reveals that the fission yeast gene, SPCC417.09c, plays a significant role in the sulfur depletion response. This gene encodes a protein with a Zn2Cys6 fungal‐type DNA‐binding domain and a transcription factor domain, and we have named it sdr1+ (sulfur depletion response 1). Interestingly, while sulfur depletion typically induces autophagy akin to nitrogen depletion, we found that autophagy was not induced under sulfur depletion in the absence of sdr1+. This suggests that sdr1+ is necessary for the induction of autophagy under conditions of sulfur depletion. Although sdr1+ is not essential for the growth of fission yeast, its overexpression, driven by the nmt1 promoter, inhibits growth. This implies that Sdr1 may possess cell growth‐inhibitory capabilities. In addition, our analysis of Δsdr1 cells revealed that sdr1+ also plays a role in regulating the expression of genes associated with the phosphate depletion response. In conclusion, our study introduces Sdr1 as a novel transcription factor that contributes to an appropriate cellular nutrient starvation response. It does so by inhibiting inappropriate cell growth and inducing autophagy in response to sulfur depletion. [ABSTRACT FROM AUTHOR]

The development of in vitro models is essential for a comprehensive understanding and investigation of pulmonary fibrosis (PF) at both cellular and molecular levels. This study presents a literature review and an analysis of various cellular models used in scientific studies, specifically focusing on their applications in elucidating the pathogenesis of PF. Our study highlights the importance of taking a comprehensive approach to studing PF, emphasizing the necessity of considering multiple cell types and organs and integrating diverse analytical perspectives. Notably, primary cells demonstrate remarkable cell growth characteristics and gene expression profiles; however, their limited availability, maintenance challenges, inability for continuous propagation and susceptibility to phenotypic changes over time significantly limit their utility in scientific investigation. By contrast, immortalized cell lines are easily accessible, cultured and continuously propagated, although they may have some phenotypic differences from primary cells. Furthermore, in vitro coculture models offer a more practical and precise method to explore complex interactions among cells, tissues and organs. Consequently, when developing models of PF, researchers should thoroughly assess the advantages, limitations and relevant mechanisms of different cell models to ensure their selection is consistent with the research objectives. [ABSTRACT FROM AUTHOR]

The direct antitumor effect of bevacizumab (BEV) has long been debated. Evidence of the direct antitumor activities of drugs are mainly obtained from in vitro experiments, which are greatly affected by experimental conditions. In this study, we evaluated the effect of BEV-containing medium renewal on the results of in vitro cytotoxicity experiments in A549 and U251 cancer cells. We observed starkly different results between the experiments with and without BEV-containing medium renewal. Specifically, BEV inhibited the tumor cell growth in the timely replacement with a BEV-containing medium but promoted tumor cell growth without medium renewal. Meanwhile, compared with the control, a significant basic fibroblast growth factor (bFGF) accumulation in the supernatant was observed in the group without medium renewal but none in that with replaced medium. Furthermore, bFGF neutralization partially reversed the pro-proliferative effect of BEV in the medium non-renewed group, while exogenous bFGF attenuated the tumor cell growth inhibition of BEV in the medium-renewed group. Our data explain the controversy over the direct antitumor effect of BEV in different studies from the perspective of the compensatory autocrine cytokines in tumor cells. [ABSTRACT FROM AUTHOR]

Conventional methods have failed to show the ability of articular cartilage to completely restore. Decellularized extracellular matrix has achieved interest as a potential biomaterial for cartilage tissue engineering approaches. The decellularized cartilage-derived matrix (CDM) scaffolds retain the native composition of cartilage tissue, providing a conducive microenvironment for cellular growth and differentiation, while exhibit limited mechanical support. Our investigation involved the fabrication of a new hybrid CDM- polyvinyl alcohol (PVA) hydrogel scaffold with four different concentrations (5%, 10%, 15%, and 20%), followed by a comprehensive characterization of the construct's physicochemical, mechanical, and biological properties to elucidate their potential in cartilage regeneration applications. Our results demonstrated that hybridization of the CDM with PVA enhanced the mechanical properties besides ensuring biocompatibility. FTIR and DSC results also confirmed the mechanical improvements in hybrid scaffolds. The hybrid CDM/PVA (15%/5%, 15%/10%, 15%/15%, and 15%/20%) scaffolds showed significantly different compressive strengths (p < 0.0001, p < 0.0004, p < 0.0001, p < 0.012 respectively). Moreover, resazurin test showed cell attachment and growth on all four types of hybrid scaffolds during seven days of three dimensional culture. The cross-linked CDM15%/PVA5% group, demonstrated acceptable mechanical strength, pore size, physicochemical properties, swelling behavior, and cell growth and attachment. Our data indicate that our hybrid CDM/PVA scaffold possess bioactive properties suitable for a promising candidate for cartilage tissue engineering studies. [ABSTRACT FROM AUTHOR]

This paper reports hybrid gels combining a low‐molecular‐weight gelator (LMWG) and a photoinitiated crosslinked polymer gel (PG). The presence of the PG enhanced the stiffness and strength of the gel. The gels were loaded with heparin, and in the hybrid gel, the interpenetrated LMWG and PG networks somewhat restricted its release. In terms of stem cell growth, the hybrid gel significantly improved the performance of the PG because of the presence of the LMWG, which is an excellent substrate for stem cells in its own right. Furthermore, the presence of heparin in the hybrid gels also enhanced stem cell proliferation over longer timescales. Finally, these gels were photopatterned within the well‐plates used for tissue culture, with patterning helping control stem cell proliferation. In summary, these hybrid gels combine the advantageous features of both LMWG and PG: rheological performance is endowed by the PG with stem cell compatibility provided by the LMWG. The hybrid gels also control the release of the bioactive agent heparin and have capacity to be shaped and patterned. Patterned gels such as these, capable of directing stem cell growth, have potential in regenerative medicine. [ABSTRACT FROM AUTHOR]

This study investigates differences in focal adhesion (FA) morphology and Talin cleavage levels between transformed and non-transformed cell lines. Utilizing fluorescently tagged wild-type Talin and Talin mutants with calpain cleavage site mutations, FA structures were visualized. Mutations in different Talin cleavage sites showed varying impacts on FA morphology and distribution across melanoma cell lines (Meljuso, A375P, A2058) and a non-transformed cell line (HFF). Western blot analysis, ratiometric fluorescence intensity-based measurements, and FRAP experiments revealed higher Talin cleavage levels within FAs of transformed cell lines compared to non-transformed cells. Additionally, growth assays indicated that reducing calpain cleavage levels attenuated transformed cell growth. These findings suggest that Talin cleavage level is crucial for FA morphology and assembly, with higher levels observed in transformed cells, influencing their growth dynamics. [ABSTRACT FROM AUTHOR]

Objective Animal Studied Procedures Results Conclusions The application of canine amniotic membrane (cAM) for corneal reconstruction is widely used in the veterinary field. However, the information on biological properties and alternative forms of cAM for corneal wound healing is limited. This study aimed to investigate the proteomic profiles and corneal wound healing properties of cAM, cAM extract (cAME), and lyophilized cAM extract (cAMX).A total number of 14 cAMs were sterilely harvested from healthy full‐term puppies and randomly divided into three different forms: cAM (n = 14), cAME (n = 14), and cAMX (n = 14).Each form of cAMs was subjected to proteomic analysis using label‐free liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS), followed by bioinformatic analysis. The proteins were classified into properties by comparing them with the literature search on human amniotic membrane (hAM) properties and the effect on corneal wound healing when given topically.The analyses identified 8136 proteins in cAM, 8211 proteins in cAME, and 7093 proteins in cAMX. A total number of 100 proteins were matched with proteins in hAM properties and were classified into anti‐inflammatory, anti‐fibrotic, anti‐microbial, anti‐angiogenic, promotion of epithelialization, analgesic, and support cell adhesion and growth properties. Furthermore, proteins with corneal wound healing effects were identified in cAME and cAMX.cAM and its extracts contain numerous proteins, including proteins related to corneal wound healing properties. Additionally, cAME and cAMX showed proteins involved in corneal wound healing and their potential benefits for topical use in ophthalmology. [ABSTRACT FROM AUTHOR]

Background: While pluripotent stem cell (PSC) therapies move toward clinical and commercial applications at a rapid rate, manufacturing reproducibility and robustness are notable bottlenecks in regulatory approval. Therapeutic applications of PSCs require large cell quantities to be generated under highly robust, well-defined, and economically viable conditions. Small-scale and short-term process optimization, however, is often performed in a linear fashion that does not account for time needed to verify the bioprocess protocols and analysis methods used. Design of a reproducible and robust bioprocess should be dynamic and include a continuous effort to understand how the process will respond over time and to different stresses before transitioning into large-scale production where stresses will be amplified. Methods: This study utilizes a baseline protocol, developed for the short-term culture of PSC aggregates in Vertical-Wheel® bioreactors, to evaluate key process attributes through long-term (serial passage) suspension culture. This was done to access overall process robustness when performed with various commercially available media and cell lines. Process output variables including growth kinetics, aggregate morphology, harvest efficiency, genomic stability, and functional pluripotency were assessed through short and long-term culture. Results: The robust nature of the expansion protocol was demonstrated over a six-day culture period where spherical aggregate formation and expansion were observed with high-fold expansions for all five commercial media tested. Profound differences in cell growth and quality were revealed only through long-term serial expansion and in-vessel dissociation operations. Some commercial media formulations tested demonstrated maintenance of cell growth rates, aggregate morphology, and high harvest recovery efficiencies through three bioreactor serial passages using multiple PSC lines. Exceptional bioprocess robustness was even demonstrated with sustained growth and quality maintenance over 10 serial bioreactor passages. However, some commercial media tested proved less equipped for serial passage cultures in bioreactors as cultures led to cell lysis during dissociation, reduction in growth rates, and a loss of aggregate morphology. Conclusions: This study demonstrates the importance of systematic selection and testing of bioprocess input variables, with multiple bioprocess output variables through serial passages to create a truly reproducible and robust protocol for clinical and commercial PSC production using scalable bioreactor systems. [ABSTRACT FROM AUTHOR]

The extraction and recovery of valuable metals from various spent catalysts via bioleaching represents a green, low-carbon and eco-friendly process. However, the pulp density of spent catalysts is usually 1.0% or lower owing to their toxicity, denoting low process capacity and poor practical potential. In this study, an intensified bioleaching strategy was used for the first time to promote the release efficiencies of both Co and Mo from a spent Co–Mo catalyst at a high pulp density of 10% by supplementing extracellular polymeric substances (EPSs). The results showed that the addition of 0.6 g L−1 EPSs harvested a maximum release of 73.6% for Co and 72.5% for Mo after 9 days of contact, with an evident elevation of 22.6% for Co and 24.4% for Mo, in contrast to no addition, respectively. The added EPS not only promoted the growth of plankton cells to produce more active molecules but also boosted the adhesion of leaching cells to the spent catalyst to form stable aggregates. Moreover, the resulting aggregates allowed for the gathering and confinement of the active small molecules, including Fe3+ and Fe2+, inside the micro-areas between the spent catalysts and the cells for quick electronic transfer as an interface oxidation/reduction reaction to free both Co and Mo from the spent catalyst. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OVC) is one of the most common causes of cancer-related deaths in women worldwide. Despite advancements in detection and therapy, the prognosis of OVC remains poor due to late diagnosis and the lack of effective therapeutic options at advanced stages. Therefore, a better understanding of the biology underlying OVC is essential for the development of effective strategies for early detection and targeted therapies. Nuclear receptors (NRs) are a superfamily of 48 transcription factors that, upon binding to their specific ligand, play a vital role in regulating various cellular processes such as growth, development, metabolism, and homeostasis. Accumulating evidence from several studies has shown that their aberrant expression is associated with multiple human diseases. Numerous NRs have shown significant effects in the development of various cancers, including OVC. This review summarizes the recent findings on the role of NRs inOVC, as well as their potential as prognostic and therapeutic markers. Further, the basic structure and signaling mechanism of NRs have also been discussed briefly. Moreover, this review highlights their cellular and molecular mechanisms in chemoresistance and chemosensitization. Further, the clinical trials targeting NRs for the treatment of OVC have also been discussed. [ABSTRACT FROM AUTHOR]

Objectives: The development of effective treatments for non-small cell lung cancer (NSCLC), particularly targeting the KRASG12C mutation, remains a challenge. In this study, we investigated the therapeutic potential of VT204, a small molecule inhibitor of KRASG12C, in NSCLC. Methods: To achieve the objectives, we conducted a comprehensive set of experimental methods. In vitro experiments involved the investigation of VT204 on proliferation, apoptosis, cell cycle dynamics, migration, invasion, and on the RAF/MEK/ERK signaling pathway in NCI-H358 cells. In addition, in vivo experiments were performed to evaluate the influence of VT204 on tumor growth. Results: We demonstrated that VT204 effectively suppressed cell proliferation in NCI-H358 cells, with significant inhibition observed at a concentration of 8 μM. Colony formation assays further supported the inhibitory effect of VT204 on NCI-H358 cell growth. Moreover, VT204 exhibited notable effects on suppressing migration and invasion capacities of NCI-H358 cells, indicating its potential as a metastasis-inhibiting agent. Mechanistic investigations revealed that VT204 induced apoptosis and G2M-phase cell cycle arrest in NCI-H358 cells. Additionally, VT204 modulated the RAF/MEK/ERK signaling pathway, leading to reduced phosphorylation of ERK. In vivo studies using xenograft models confirmed the inhibitory effect of VT204 on NCI-H358 tumor growth. Conclusion: These findings highlight VT204 as a promising therapeutic candidate for NSCLC targeting the KRASG12C mutation. [ABSTRACT FROM AUTHOR]

Prolyl oligopeptidase (POP) is a conserved serine protease belonging to proline-specific peptidases. It has both enzymatic and non-enzymatic activity and is involved in numerous biological processes in the human body, playing a role in e.g., cellular growth and differentiation, inflammation, as well as the development of some neurodegenerative and neuropsychiatric disorders. This article describes the physiological and pathological aspects of POP activity and the state-of-art of its peptidic inhibitors originating from food proteins, with a particular focus on their potential as cognition-enhancing agents. Although some milk, meat, fish, and plant protein-derived peptides have the potential to be applied as natural, procognitive nutraceuticals, their effectiveness requires further evaluation, especially in clinical trials. We demonstrated that the important features of the most promising POP-inhibiting peptides are very short sequence, high content of hydrophobic amino acids, and usually the presence of proline residue. [ABSTRACT FROM AUTHOR]

Abstract\nNOVELTY STATEMENTThallium (Tl), a key element in high-tech industries, is recognized as a priority pollutant by the US EPA and EC. Tl accumulation threatens aquatic ecosystems. Despite its toxicity, little is known about its impact on cyanobacteria. This study explores the biochemical mechanisms of Tl(I) toxicity in cyanobacteria, focusing on physiology, metabolism, oxidative damage, and antioxidant responses. To this end, Anabaena and Nostoc were exposed to 400 µg/L, and 800 µg/L of Tl(I) over seven days. Anabaena showed superior Tl(I) accumulation with 7.8% removal at 400 µg/L and 9.5% at 800 µg/L, while Nostoc removed 2.2% and 7.4%, respectively. Tl(I) exposure significantly reduced the photosynthesis rate and function, more than in Nostoc. It also altered primary metabolism, increasing sugar levels and led to higher amino and fatty acids levels. While Tl(I) induced cellular damage in both species, Anabaena was less affected. Both species enhanced their antioxidant defense systems, with Anabaena showing a 175.6% increase in SOD levels under a high Tl(I) dose. This suggests that Anabaena’s robust biosorption and antioxidant systems could be effective for Tl(I) removal. The study improves our understanding of Tl(I) toxicity, tolerance, and phycoremediation in cyanobacteria, aiding future bioremediation strategies.This study presents novel insights into thallium (Tl) phycoremediation using Anabaena laxa and Nostoc muscorum, crucial for addressing the increasing contamination concerns stemming from high-tech industries. Elucidating the tolerance mechanisms and physiological responses of these cyanobacterial species to Tl(I) exposure. It highlights the potential of Anabaena laxa as an effective bio-remediator, offering a sustainable solution to mitigate Tl(I) environmental impact. [ABSTRACT FROM AUTHOR]

Human estrogen receptor alpha (ERα) is considered an important target, especially in the treatment of breast cancer, as it has a vital role in cancer development. ERα-targeted therapies generally target the ligand binding domain (LBD) of ERα. However, over time, cells develop resistance to this mechanism alternative approaches to inhibit ERα activity target ERα–DNA or ERα–cofactor interactions. Inhibitors of ERα–cofactor interactions are designed by targeting the hydrophobic hollow region of the receptor box LXXLL motif.In this context, helix-stabilized cyclic peptides (SPs) designed with in silico approaches were obtained by solid phase peptide synthesis. The effects of SPs on MCF-7 cells were examined with MTT and ATP, and qPCR and flow cytometry were used for further analysis.Our results demonstrated that the SPs were effective only in MCF-7 cells expressing ERα. In addition, cyclic peptide combinations (SPCs) showed anti-proliferative and toxic effects on MCF-7 cells. The impact of SPCs with the highest inhibitory effect in MCF-7 cells on ERα-related genes and markers of apoptosis was revealed. Moreover, the flow cytometry analysis result used to examine apoptotic cells proved the apoptosis of SPCs in MCF-7 cells.These findings suggest that our novel SPs, which inhibit coactivator interactions of ERα, induce apoptosis of MCF-7 cells. Thus, considering this strong effect of SPs in the inhibition of receptors, it is pointed out that they can be further developed as an alternative to current clinical treatments or as an auxiliary approach in the generating of new targeted peptide-based therapies. [ABSTRACT FROM AUTHOR]

BACKGROUND: silencing information regulatory 1 (SIRT1) regulates the function of related proteins in chondrocytes in a deacetylated manner and participates in chondrocyte proliferation and differentiation, thereby promoting cartilage defect repair. OBJECTIVE: To screen for signaling pathways with unclear action status after SIRT1 gene knockdown in chondrocytes, as well as diseases or functions that produce changes using high-throughput technology. METHODS: ATDC5 chondrocytes from mice in logarithmic growth phase were divided into two groups: the cells were transfected with SIRT1 gene knockdown negative control lentivirus in control group and SIRT1 gene knockdown lentivirus in experimental group. GeneChip® Mouse Genome 430 2.0 Array was used to detect the mRNA expression at 72 hours after transfection. Applied bioinformatics technology was also used to screen for unclear activation or inhibition signaling pathways and their related factors. Moreover, enrichment of disease or function modules was analyzed. RESULTS AND CONCLUSION: After knocking down the SIRT1 gene, there were 245 signaling pathways with unclear activation or inhibition status in the mouse ATDC5 chondrocytes. According to the ranking of -Log (P-value), we reported the factors in the top 20 signaling pathways with unclear activation or inhibition status, including IGFBP4, TGFBR1, CTGF, COL4A5, LHX2, IL1RL1, and KLF6. According to the ranking of -Log (P-value), there were significant changes in 14 disease or function modules, including cellular growth and proliferation, organism survival, cell death and survival. According to the number of differentially expressed genes, there were significant changes in three disease or function modules, including organismal injury and abnormalities, cancer, and cell death and survival. According to the comprehensive ranking of -Log (P-value) and the number of differentially expressed genes, the disease or function module related to intrinsic immune response was significantly activated. [ABSTRACT FROM AUTHOR]

Droplet encapsulations using liquid or solid shells are of significant interest in microreactors, drug delivery, crystallization, and cell growth applications. Despite progress in droplet-related technologies, tuning micron-scale shell thickness over a large range of droplet sizes is still a major challenge. In this work, we report capillary force assisted cloaking using hydrophobic colloidal particles and liquid-infused surfaces. The technique produces uniform solid and liquid shell encapsulations over a broad range (5–200 μm shell thickness for droplet volume spanning over four orders of magnitude). Tunable liquid encapsulation is shown to reduce the evaporation rate of droplets by up to 200 times with a wide tunability in lifetime (1.5 h to 12 days). Further, we propose using the technique for single crystals and cell/spheroid culture platforms. Stimuli-responsive solid shells show hermetic encapsulation with tunable strength and dissolution time. Moreover, scalability, and versatility of the technique is demonstrated for on-chip applications. Encapsulated liquids are important for several microreactor applications, including (bio)chemistry in confined spaces. Here, the authors report on oil-infused particle shells that allow control of shell thickness, stability, and permeability for applications in crystal growth and cell cultivation. [ABSTRACT FROM AUTHOR]

Mass spectrometry-based omics technologies are increasingly used in perturbation studies to map drug effects to biological pathways by identifying significant molecular events. Significance is influenced by fold change and variation of each molecular parameter, but also by multiple testing corrections. While the fold change is largely determined by the biological system, the variation is determined by experimental workflows. Here, it is shown that memory effects of prior subculture can influence the variation of perturbation profiles using the two colon carcinoma cell lines SW480 and HCT116. These memory effects are largely driven by differences in growth states that persist into the perturbation experiment. In SW480 cells, memory effects combined with moderate treatment effects amplify the variation in multiple omics levels, including eicosadomics, proteomics, and phosphoproteomics. With stronger treatment effects, the memory effect was less pronounced, as demonstrated in HCT116 cells. Subculture homogeneity was controlled by real-time monitoring of cell growth. Controlled homogeneous subculture resulted in a perturbation network of 321 causal conjectures based on combined proteomic and phosphoproteomic data, compared to only 58 causal conjectures without controlling subculture homogeneity in SW480 cells. Some cellular responses and regulatory events were identified that extend the mode of action of arsenic trioxide (ATO) only when accounting for these memory effects. Controlled prior subculture led to the finding of a synergistic combination treatment of ATO with the thioredoxin reductase 1 inhibitor auranofin, which may prove useful in the management of NRF2-mediated resistance mechanisms. [ABSTRACT FROM AUTHOR]

TOR complex 1 (TORC1) is a multi‐protein kinase complex that coordinates cellular growth with environmental cues. Recent studies have identified Pib2 as a critical activator of TORC1 in budding yeast. Here, we show that loss of Pib2 causes severe growth defects in fission yeast cells, particularly when basal TORC1 activity is diminished by hypomorphic mutations in tor2, the gene encoding the catalytic subunit of TORC1. Consistently, TORC1 activity is significantly compromised in the tor2 hypomorphic mutants lacking Pib2. Moreover, as in budding yeast, fission yeast Pib2 localizes to vacuolar membranes via its FYVE domain, with its tail motif indispensable for TORC1 activation. These results strongly suggest that Pib2‐mediated positive regulation of TORC1 is evolutionarily conserved between the two yeast species. [ABSTRACT FROM AUTHOR]

Our study employs pooled CRISPR screens, integrating 2D and 3D culture models, to identify miRNAs critical in Breast Cancer (BC) tumoursphere formation. These screens combine with RNA-seq experiments allowing identification of miRNA signatures and targets essential for tumoursphere growth. miR-4787-3p exhibits significant up-regulation in BC, particularly in basal-like BCs, suggesting its association with aggressive disease. Surprisingly, despite its location within the 5'UTR of a protein coding gene, which defines DROSHA-independent transcription start site (TSS)-miRNAs, we find it dependant on both DROSHA and DICER1 for maturation. Inhibition of miR-4787-3p hinders tumoursphere formation, highlighting its potential as a therapeutic target in BC. Our study proposes elevated miR-4787-3p expression as a potential prognostic biomarker for adverse outcomes in BC. We find that protein-coding genes positively selected in the CRISPR screens are enriched of miR-4787-3p targets. Of these targets, we select ARHGAP17, FOXO3A, and PDCD4 as known tumour suppressors in cancer and experimentally validate the interaction of miR-4787-3p with their 3'UTRs. Our work illuminates the molecular mechanisms underpinning miR-4787-3p's oncogenic role in BC. These findings advocate for clinical investigations targeting miR-4787-3p and underscore its prognostic significance, offering promising avenues for tailored therapeutic interventions and prognostic assessments in BC. A CRISPR/Cas9 genome wide screen in 2D breast cancer and 3D tumourspheres cultures identifies miR-4787-3p as a transcriptional tart site miRNA essential for breast tumour-initiating cell growth. [ABSTRACT FROM AUTHOR]