Effect of industrial alkene ozonolysis on atmospheric H2SO4 formation.

This study has employed the master chemical mechanism (MCM) to investigate the influence of the ozone oxidation pathways in the atmospheric formation of H2SO4 from short-chain olefins in industrialized areas. In-situ H2SO4 formation data were obtained using a high-resolution chemical ionization time-of-flight mass spectrometer, and the simulated H2SO4 concentrations calculated using updated parameters for the MCM model exhibited good agreement with observations. In the simulation analysis of different reaction pathways involved in H2SO4 formation, hydroxyl radicals were found to dominate H2SO4 production during the daytime, while olefin ozone oxidation contributed up to 65% of total H2SO4 production during the night-time. A sensitivity analysis of the H2SO4 production parameters has revealed a high sensitivity to changes in sulfur dioxide, and a relatively high sensitivity to olefins with fast ozonolysis reaction rates and bimolecular reaction rates of resulting stabilized Criegee Intermediates. A high relative humidity promotes daytime H2SO4 formation, but has an inhibiting effect during the night-time due to the different dominant reaction pathways.

Antimicrobial Hydroxyethyl-Cellulose-Based Composite Films with Zinc Oxide and Mesoporous Silica Loaded with Cinnamon Essential Oil.

Background: Cellulose derivatives are gaining much attention in medical research due to their excellent properties such as biocompatibility, hydrophilicity, non-toxicity, sustainability, and low cost. Unfortunately, cellulose does not exhibit antimicrobial activity. However, derivatives like hydroxyethyl cellulose represent a proper matrix to incorporate antimicrobial agents with beneficial therapeutic effects. Methods: Combining more antimicrobial agents into a single composite material can induce stronger antibacterial activity by synergism. Results: Therefore, we have obtained a hydroxyethyl-cellulose-based material loaded with zinc oxide nanoparticles and cinnamon essential oil as the antimicrobial agents. The cinnamon essential oil was loaded in mesoporous silica particles to control its release. Conclusions: The composite films demonstrated high antibacterial activity against Staphylococcus aureus and Escherichia coli strains, impairing the bacterial cells' viability and biofilm development. Such antimicrobial films can be used in various biomedical applications such as topical dressings or as packaging for the food industry.

Multifaceted role of the DNA replication protein MCM10 in maintaining genome stability and its implication in human diseases.

MCM10 plays a vital role in genome duplication and is crucial for DNA replication initiation, elongation, and termination. It coordinates several proteins to assemble at the fork, form a functional replisome, trigger origin unwinding, and stabilize the replication bubble. MCM10 overexpression is associated with increased aggressiveness in breast, cervical, and several other cancers. Disruption of MCM10 leads to altered replication timing associated with initiation site gains and losses accompanied by genome instability. Knockdown of MCM10 affects the proliferation and migration of cancer cells, manifested by DNA damage and replication fork arrest, and has recently been shown to be associated with clinical conditions like CNKD and RCM. Loss of MCM10 function is associated with impaired telomerase activity, leading to the accumulation of abnormal replication forks and compromised telomere length. MCM10 interacts with histones, aids in nucleosome assembly, binds BRCA2 to maintain genome integrity during DNA damage, prevents lesion skipping, and inhibits PRIMPOL-mediated repriming. It also interacts with the fork reversal enzyme SMARCAL1 and inhibits fork regression. Additionally, MCM10 undergoes several post-translational modifications and contributes to transcriptional silencing by interacting with the SIR proteins. This review explores the mechanism associated with MCM10's multifaceted role in DNA replication initiation, chromatin organization, transcriptional silencing, replication stress, fork stability, telomere length maintenance, and DNA damage response. Finally, we discuss the role of MCM10 in the early detection of cancer, its prognostic significance, and its potential use in therapeutics for cancer treatment.

Identification of biallelic mutations in MCM3AP and comprehensive literature analysis.

Background: Minichromosome maintenance complex component 3 associated protein (MCM3AP) is a gene in which mutations can result in autosomal recessive peripheral neuropathy with or without impaired intellectual development. The MCM3AP genotype-phenotype correlation and prognosis remain unclear. The aim of this study was to explore the genotype-phenotype correlations pertaining to MCM3AP. Methods: Whole-exome sequencing (WES) combined with copy number variation sequencing (CNV-seq) were performed on the genomic DNA isolated from a Chinese family, and Sanger sequencing, quantitative PCR and cDNA analyses were performed to examine the mutations. The retrospective study was conducted on 28 individuals with biallelic MCM3AP mutation-related diseases, including features such as mutations, motor development impairment, intellectual disability, weakness/atrophy, and cerebral magnetic resonance imaging abnormalities. Results: Sequencing identified novel compound heterozygous mutations in MCM3AP, namely, a paternal variant c.1_5426del (loss of exons 1-25) and a maternal splicing variant c.1858 + 3A>G. Functional studies revealed that the variant c.1858 + 3A>G resulted in the heterozygous deletion of exon 5, thereby affecting splicing functionality. Furthermore, the compound heterozygous mutation may affect the functionality of the protein domain. Retrospective analysis revealed different genotype-phenotype correlations for the pathogenic variants in biallelic MCM3AP: all individuals (100%) with mutations outside the Sac3 domain exhibited early-onset symptoms, motor developmental delays, and cognitive abnormalities, conversely, the proportions of individuals carrying mutations within the domain were 26.7% (motor delays) and 46.7% (cognitive abnormalities). Conclusion: Our findings further expand the genetic mutation spectrum of biallelic MCM3AP and highlight the genotype-phenotype associations. Additionally, we elaborate on the importance of rehabilitation intervention.

Integrating Mcm-2 and Ki-67 immunohistochemistry with clinico-pathologic parameters for enhanced prognostic accuracy in oral verrucous lesions.

BACKGROUND: Oral verrucous lesions (OVLs) present a diagnostic challenge due to their diverse and often confusing histopathological features. Accurate differentiation is essential for improving diagnosis and predicting prognosis. In addition to assessing overall survival (OS) and disease-free survival (DFS) in verrucous squamous cell carcinoma (VSCC) and conventional OSCC, this study seeks to evaluate the expression of Mcm-2 and Ki-67 in verrucous lesions and oral squamous cell carcinoma (OSCC). These findings will be correlated with the nuclear expression of Mcm-2 and Ki-67. METHODOLOGY: Ninety tissue samples that were paraffin embedded and formalin-fixed were examined using immunohistochemistry to determine the expression of Mcm-2 and Ki-67. Data on survival and clinico-pathologic characteristics were taken from patient records. Statistical analyses were conducted using Independent T-tests, Cox regression models, and Kaplan-Meier survival analysis. RESULTS: Mcm-2 was identified as a more sensitive and prognostic marker compared to Ki-67 across the study groups. Mcm-2 overexpression was observed in all cases of verrucous hyperplasia with dysplasia, verrucous carcinoma (VC), VSCC, and conventional OSCC. The 3-year OS and DFS rates were lower in conventional OSCC (75 % and 64.3 %, respectively) compared to VSCC (90 % and 70 %). CONCLUSION: This study represents the first initiative to employ both Mcm-2 and Ki-67 as proliferative markers for distinguishing between various oral verrucous lesions. Mcm-2 proves to be a valuable marker for differentiating between potentially malignant and malignant verrucous lesions. However, further validation with larger sample sizes and longer follow-up periods is necessary to confirm its role in predicting OS and DFS.

Understanding microbial biomineralization at the molecular level: recent advances.

Microbial biomineralization is a phenomenon involving deposition of inorganic minerals inside or around microbial cells as a direct consequence of biogeochemical cycling. The microbial metabolic processes often create environmental conditions conducive for the precipitation of silicate, carbonate or phosphate, ferrate forms of ubiquitous inorganic ions. Till date the fundamental mechanisms underpinning two of the major types of microbial biomineralization such as, microbially controlled and microbially induced remains poorly understood. While microbially-controlled mineralization (MCM) depends entirely on the genetic makeup of the cell, microbially-induced mineralization (MIM) is dependent on factors such as cell morphology, cell surface structures and extracellular polymeric substances (EPS). In recent years, the organic template-mediated nucleation of inorganic minerals has been considered as an underlying mechanism based on the principles of solid-state bioinorganic chemistry. The present review thus attempts to provide a comprehensive and critical overview on the recent progress in holistic understanding of both MCM and MIM, which involves, organic-inorganic biomolecular interactions that lead to template formation, biomineral nucleation and crystallization. Also, the operation of specific metabolic pathways and molecular operons in directing microbial biomineralization have been discussed. Unravelling these molecular mechanisms of biomineralization can help in the biomimetic synthesis of minerals for potential therapeutic applications, and facilitating the engineering of microorganisms for commercial production of biominerals.

Wintertime ozone surges: The critical role of alkene ozonolysis.

Ozone (O3) pollution is usually linked to warm weather and strong solar radiation, making it uncommon in cold winters. However, an unusual occurrence of four high O3 episode days (with maximum hourly concentrations exceeding 100 ppbv and peaking at 121 ppbv) was recorded in January 2018 in Lanzhou city, China. During these episodes, the average daytime concentration of total non-methane volatile organic compounds (TVOCs) reached 153.4 ± 19.0 ppbv, with alkenes-largely emitted from the local petrochemical industry-comprising 82.3 ± 13.1 ppbv. Here we show a photochemical box model coupled with a Master Chemical Mechanism to elucidate the mechanisms behind this unusual wintertime O3 pollution. We find that the typically low temperatures (-1.7 ± 1.3 °C) and weak solar radiation (263.6 ± 60.7 W m- 2) of those winter episode days had a minimal effect on the reactivity of VOCs with OH radicals. Instead, the ozonolysis of alkenes generated Criegee intermediates, which rapidly decomposed into substantial RO x radicals (OH, HO2, and RO2) without sunlight. This radical production led to the oxidation of VOCs, with alkene ozonolysis ultimately contributing to 89.6 ± 8.7% of the O3 formation during these episodes. This mechanism did not activate at night due to the depletion of O3 by the NO titration effect. Furthermore, the findings indicate that a reduction of alkenes by 28.6% or NO x by 27.7% in the early afternoon could significantly mitigate wintertime O3 pollution. Overall, this study unravels the unique mechanism of alkene-induced winter O3 pollution and offers a reference for winter O3 reduction strategies in the petrochemical industrial regions.

Expression, potential biological behaviour and clinical significance of MCM3 in pancreatic adenocarcinoma: a comprehensive study integrating high throughput sequencing, CRISPR screening and in-house immunohistochemistry.

BACKGROUND: Minichromosome maintenance complex component 3 (MCM3) plays a key role in various tumours. However, it remains largely unknown what the specific role and clinical significance of MCM3 in pancreatic adenocarcinoma (PAAD) are. MATERIALS AND METHODS: We integrated high-throughput data from PAAD worldwide to analyse the expression level of MCM3 mRNA. We used immunohistochemistry to analyse MCM3 protein expression levels in 145 cases in the PAAD group and 29 cases in the non-PAAD group. We also mainly analysed the necessity of MCM3 for PAAD growth based on CRISPR screen data. In addition, we used enrichment analysis and protein-protein interaction networks to explore the molecular mechanism of MCM3 in PAAD. We also analysed the correlation between MCM3 expression, components of the immune microenvironment in PAAD tissue and clinical prognosis. RESULTS: In PAAD, we observed for the first time that MCM3 was significantly highly expressed at both the mRNA (SMD = 0.67, 95% CI: 0.38 ∼ 0.96) and the protein level (p < 0.05). The mRNA (AUC = 0.78, 95% CI: 0.74 ∼ 0.81; sensitivity = 0.66, 95% CI: 0.55 ∼ 0.76; specificity = 0.76, 95% CI: 0.67 ∼ 0.84) and protein (AUC = 0.929) expression levels of MCM3 had a good ability to distinguish between PAAD and non-PAAD tissue. There was heterogeneity reflected by the differential expression of MCM3 protein in PAAD cells. MCM3 played an essential role in PAAD growth, through abnormal DNA replication, p53 signalling and cell cycle checkpoints. PAAD with high MCM3 expression was sensitive to c-75, brivanib, flavopiridol and VNLG/124 drugs, with stable molecular docking models. CONCLUSION: MCM3 is likely to be a critical element in promoting the initiation and growth of PAAD. Flavopiridol may exert its anti-PAAD effect through the interaction between MCM3, classic CDK1 targets in the cell cycle checkpoint and p53 pathway as well as related molecules in other pathways.

MCM3 could potentially play a crucial role in promoting the onset and growth of PAAD.There is heterogeneity reflected by the differential expression of MCM3 protein in PAAD cells.The interplay between MCM3, well-established CDK1 targets in the cell cycle checkpoint and p53 pathway, along with relevant molecules in other pathways, may mediate the anti-pancreatic adenocarcinoma (PAAD) effect of flavopiridol.

Mrc1 regulates parental histone segregation and heterochromatin inheritance.

Chromatin-based epigenetic memory relies on the symmetric distribution of parental histones to newly synthesized daughter DNA strands, aided by histone chaperones within the DNA replication machinery. However, the mechanism of parental histone transfer remains elusive. Here, we reveal that in fission yeast, the replisome protein Mrc1 plays a crucial role in promoting the transfer of parental histone H3-H4 to the lagging strand, ensuring proper heterochromatin inheritance. In addition, Mrc1 facilitates the interaction between Mcm2 and DNA polymerase alpha, two histone-binding proteins critical for parental histone transfer. Furthermore, Mrc1's involvement in parental histone transfer and epigenetic inheritance is independent of its known functions in DNA replication checkpoint activation and replisome speed control. Instead, Mrc1 interacts with Mcm2 outside of its histone-binding region, creating a physical barrier to separate parental histone transfer pathways. These findings unveil Mrc1 as a key player within the replisome, coordinating parental histone segregation to regulate epigenetic inheritance.

Theranostics Using MCM-41-Based Mesoporous Silica Nanoparticles: Integrating Magnetic Resonance Imaging and Novel Chemotherapy for Breast Cancer Treatment.

Advanced breast cancer remains a significant oncological challenge, requiring new approaches to improve clinical outcomes. This study investigated an innovative theranostic agent using the MCM-41-NH2-DTPA-Gd3⁺-MIH nanomaterial, which combined MRI imaging for detection and a novel chemotherapy agent (MIH 2.4Bl) for treatment. The nanomaterial was based on the mesoporous silica type, MCM-41, and was optimized for drug delivery via functionalization with amine groups and conjugation with DTPA and complexation with Gd3+. MRI sensitivity was enhanced by using gadolinium-based contrast agents, which are crucial in identifying early neoplastic lesions. MIH 2.4Bl, with its unique mesoionic structure, allows effective interactions with biomolecules that facilitate its intracellular antitumoral activity. Physicochemical characterization confirmed the nanomaterial synthesis and effective drug incorporation, with 15% of MIH 2.4Bl being adsorbed. Drug release assays indicated that approximately 50% was released within 8 h. MRI phantom studies demonstrated the superior imaging capability of the nanomaterial, with a relaxivity significantly higher than that of the commercial agent Magnevist. In vitro cellular cytotoxicity assays, the effectiveness of the nanomaterial in killing MDA-MB-231 breast cancer cells was demonstrated at an EC50 concentration of 12.6 mg/mL compared to an EC50 concentration of 68.9 mg/mL in normal human mammary epithelial cells (HMECs). In vivo, MRI evaluation in a 4T1 syngeneic mouse model confirmed its efficacy as a contrast agent. This study highlighted the theranostic capabilities of MCM-41-NH2-DTPA-Gd3⁺-MIH and its potential to enhance breast cancer management.

MCM-41 supported 2-aminothiophenol/Cu complex as a sustainable nanocatalyst for Suzuki coupling reaction.

We have developed an innovative mesoporous nanocatalyst by carefully attaching a 2-aminothiophenol-Cu complex onto functionalized MCM-41. This straightforward synthesis process has yielded a versatile nanocatalyst known for its outstanding efficiency, recyclability, and enhanced stability. The structural integrity of the nanocatalyst was comprehensively analyzed using an array of techniques, including BET (Brunauer-Emmett-Teller) for surface area measurement, ICP (Inductively Coupled Plasma) for metal content determination, EDS (Energy-Dispersive X-ray Spectroscopy) for elemental mapping, XRD (X-ray Diffraction) for crystalline structure elucidation, SEM (Scanning Electron Microscopy), EMA (Elemental Mapping Analysis), TEM (Transmission Electron Microscopy), TGA (Thermogravimetric Analysis), FT-IR (Fourier Transform Infrared Spectroscopy), AFM (Atomic Force Microscopy), and CV (cyclic voltammetry). Subsequently, the catalytic properties of the newly developed MCM-41-CPTEO-2-aminothiophenol-Cu catalyst was evaluated in the synthesis of biphenyls, demonstrating outstanding yields through a Suzuki coupling reaction between phenylboronic acid and aryl halides. Importantly, this reaction was conducted in an environmentally friendly medium. Note the remarkable recyclability of the catalyst, proving its sustainability over six cycles with minimal loss in activity additionally hot filtration test was prepared to examine the stability of this nanocatalyst. This outstanding feature emphasizes the catalyst's potential for long-term, environmentally conscious catalytic applications.

A High-Quality Mixed Matrix Membrane with Nanosheets Assembled and Uniformly Dispersed Fillers for Ethanol Recovery.

A high-quality filler within mixed matrix membranes, coupled with uniform dispersity, endows a high-efficiency transfer pathway for the significant improvement on separation performance. In this work, a zeolite-typed MCM-22 filler is reported that is doped into polydimethylsiloxane (PDMS) matrix by ultrafast photo-curing technique. The unique structure of nanosheets assembly layer by layer endows the continuous transfer channels towards penetrate molecules because of the inter-connective nanosheets within PDMS matrix. Furthermore, an ultrafast freezing effect produced by fast photo-curing is used to overcome the key issue, namely filler aggregation, and further eliminates defects. When pervaporative separating a 5 wt% ethanol aqueous solution, the resulting MCM-22/PDMS membrane exhibits an excellent membrane flux of 1486 g m-2 h-1 with an ethanol separation factor of 10.2. Considering a biobased route for ethanol production, the gas stripping and vapor permeation through this membrane also shows a great enrichment performance, and the concentrated ethanol is up to 65.6 wt%. Overall, this MCM-22/PDMS membrane shows a high separation ability for ethanol benefited from a unique structure deign of fillers and ultrafast curing speed of PDMS, and has a great potential for bioethanol separation from cellulosic ethanol fermentation.

In vitro observation of histone-hexamer association with and dissociation from the amino-terminal region of budding yeast Mcm2, a subunit of the replicative helicase.

During DNA replication, core histones that form nucleosomes on template strands are evicted and associate with newly synthesized strands to reform nucleosomes. Mcm2, a subunit of the Mcm2-7 complex, which is a core component of the replicative helicase, interacts with histones in the amino-terminal region (Mcm2N) and is involved in the parental histone recycling to lagging strands. Herein, the interaction of Mcm2N with histones was biochemically analyzed to reveal the molecular mechanisms underlying histone recycling by Mcm2N. With the addition of Mcm2N, a histone hexamer, comprising a H3-H4 tetramer and a H2A-H2B dimer, was excised from the histone octamer to form a complex with Mcm2N. The histone hexamer, but not H3-H4 tetramer was released from Mcm2N in the presence of Nap1, a histone chaperone. FACT, another histone chaperone, stabilized Mcm2N-histone hexamer complex to protect from Nap1-dependent dissociation. This study indicates cooperative histone transfer via Mcm2N and histone chaperones.

Dynamics of Replication-Associated Protein Levels through the Cell Cycle.

The measurement of dynamic changes in protein level and localization throughout the cell cycle is of major relevance to studies of cellular processes tightly coordinated with the cycle, such as replication, transcription, DNA repair, and checkpoint control. Currently available methods include biochemical assays of cells in bulk following synchronization, which determine protein levels with poor temporal and no spatial resolution. Taking advantage of genetic engineering and live-cell microscopy, we performed time-lapse imaging of cells expressing fluorescently tagged proteins under the control of their endogenous regulatory elements in order to follow their levels throughout the cell cycle. We effectively discern between cell cycle phases and S subphases based on fluorescence intensity and distribution of co-expressed proliferating cell nuclear antigen (PCNA)-mCherry. This allowed us to precisely determine and compare the levels and distribution of multiple replication-associated factors, including Rap1-interacting factor 1 (RIF1), minichromosome maintenance complex component 6 (MCM6), origin recognition complex subunit 1 (ORC1, and Claspin, with high spatiotemporal resolution in HeLa Kyoto cells. Combining these data with available mass spectrometry-based measurements of protein concentrations reveals the changes in the concentration of these proteins throughout the cell cycle. Our approach provides a practical basis for a detailed interrogation of protein dynamics in the context of the cell cycle.

Antibacterial properties of mesoporous silica coated with cerium oxide nanoparticles in dental resin composite.

Cerium oxide nanoparticles are known for their antibacterial effects resulting from Ce3+ to Ce4+ conversion. Application of such cerium oxide nanoparticles in dentistry has been previously considered but limited due to deterioration of mechanical properties. Hence, this study aimed to examine mesoporous silica (MCM-41) coated with cerium oxide nanoparticles and evaluate the antibacterial effects and mechanical properties when applied to dental composite resin. Cerium oxide nanoparticles were coated on the MCM-41 surface using the sol-gel method by adding cerium oxide nanoparticle precursor to the MCM-41 dispersion. The samples were tested for antibacterial activity against Streptococcus mutans via CFU and MTT assays. The mechanical properties were assessed by flexural strength and depth of cure according to ISO 4049. Data were analyzed using a t-test, one-way ANOVA, and Tukey's post-hoc test (p = 0.05). The experimental group showed significantly increased antibacterial properties compared to the control groups (p < 0.005). The flexural strength exhibited a decreasing trend as the amount of cerium oxide nanoparticle-coated MCM-41 increased. However, the flexural strength and depth of cure values of the silane group met the ISO 4049 standard. Antibacterial properties increased with increasing amounts of cerium oxide nanoparticles. Although the mechanical properties decreased, silane treatment overcame this drawback. Hence, the cerium oxide nanoparticles coated on MCM-41 may be used for dental resin composite.

Zirconium Phosphate-Pillared Zeolite MCM-36 for Green Production of γ-Valerolactone from Levulinic Acid via Catalytic Transfer Hydrogenation.

γ-valerolactone (GVL), derived from biomass, is a crucial platform compound for biofuel synthesis and various industrial applications. Current methods for synthesizing GVL involve expensive catalysts and high-pressure hydrogen, prompting the search for greener alternatives. This study focuses on a novel zirconium phosphate (ZrP)-pillared zeolite MCM-36 derivative catalyst for converting levulinic acid (LA) to GVL using alcohol as a hydrogen source. The incorporation of ZrP significantly contributes to mesoporosity and greatly enhances the acidity of the catalysts. Additionally, we employed 31P MAS NMR to comprehensively investigate the influence of phosphorus species on both the acidity and the catalytic conversion of LA to GVL. By adjusting the Zr-to-P ratios, we synthesized catalysts with enhanced acidity, achieving high conversion of LA and selectivity for GVL. The catalyst exhibited high recyclability, showing only minor deactivation over the course of five cycles. Furthermore, the catalyst was successfully applied to the one-pot conversion of furfural to GVL, showcasing its versatility in biomass conversion. This study highlights the potential of the MCM-ZrP1 catalyst for sustainable biomass conversion and offers insights for future research in renewable energy technologies.

The Role of the MCM2-7 Helicase Subunit MCM2 in Epigenetic Inheritance.

Recycling histone proteins from parental chromatin, a process known as parental histone transfer, is an important component in chromosome replication and is essential for epigenetic inheritance. We review recent advances in our understanding of the recycling mechanism of parental histone H3-H4 tetramers (parH3:H4tet), emphasizing the pivotal role of the DNA replisome. In particular, we highlight the function of the MCM2-7 helicase subunit Mcm2 as a histone H3-H4 tetramer chaperone. Disruption of this histone chaperone's functions affects mouse embryonic stem cell differentiation and can lead to embryonic lethality in mice, underscoring the crucial role of the replisome in maintaining epigenomic stability.

Assembly, Activation, and Helicase Actions of MCM2-7: Transition from Inactive MCM2-7 Double Hexamers to Active Replication Forks.

In this review, we summarize the processes of the assembly of multi-protein replisomes at the origins of replication. Replication licensing, the loading of inactive minichromosome maintenance double hexamers (dhMCM2-7) during the G1 phase, is followed by origin firing triggered by two serine-threonine kinases, Cdc7 (DDK) and CDK, leading to the assembly and activation of Cdc45/MCM2-7/GINS (CMG) helicases at the entry into the S phase and the formation of replisomes for bidirectional DNA synthesis. Biochemical and structural analyses of the recruitment of initiation or firing factors to the dhMCM2-7 for the formation of an active helicase and those of origin melting and DNA unwinding support the steric exclusion unwinding model of the CMG helicase.

Systemic Pharmacotherapeutic Treatment of the ACTA1-MCM/FLExDUX4 Preclinical Mouse Model of FSHD.

Aberrant expression of the double homeobox 4 (DUX4) gene in skeletal muscle predominantly drives the pathogenesis of facioscapulohumeral muscular dystrophy (FSHD). We recently demonstrated that berberine, an herbal extract known for its ability to stabilize guanine-quadruplex structures, effectively downregulates DUX4 expression in FSHD patient-derived myoblasts and in mice overexpressing exogenous DUX4 after viral vector-based treatment. Here, we sought to confirm berberine's inhibitory efficacy on DUX4 in the widely used FSHD-like transgenic mouse model, ACTA1-MCM/FLExDUX4, where DUX4 is induced at pathogenic levels using tamoxifen. Animals repeatedly treated with berberine via intraperitoneal injections for 4 weeks exhibited significant reductions in both mRNA and protein levels of DUX4, and in mRNA expression of murine DUX4-related genes. This inhibition translated into improved forelimb muscle strength and positive alterations in important FSHD-relevant cellular pathways, although its impact on muscle mass and histopathology was less pronounced. Collectively, our data confirm the efficacy of berberine in downregulating DUX4 expression in the most relevant FSHD mouse model. However, further optimization of dosing regimens and new studies to enhance the bioavailability of berberine in skeletal muscle are warranted to fully leverage its therapeutic potential for FSHD treatment.

Utilizing silica fume and synthetically produced mesoporous silicas for simulated flue gas CO2 adsorption.

Carbon capture and storage (CCS) is crucial in mitigating greenhouse gas emissions. Solid adsorbents, notable for their reusability and corrosion resistance, are gaining attention in CO2 gas separation. This study uses Silica fume as an adsorbent and silica source for SiO2 and MCM-41 silica-based adsorbents. Silica was extracted via an alkaline dissolution method, and adsorbents were synthesized using a CO2-induced precipitation method, chosen for its shorter synthesis time and CO2 utilization. The effects of pore volume, average pore diameter, and specific surface area on amine loading and CO2 adsorption capacity were investigated using CTAB surfactant in SiO2 synthesis, resulting in MCM-41. The synthesized adsorbents were modified with TEPA and DEA amines due to their high affinity for CO2. After determining optimal amine loading, the impact of combining TEPA with DEA was examined. The highest CO2 adsorption capacity under simulated flue gas conditions (15% volume CO2 and 85% volume N2) was 198 milligrams per gram of adsorbent for the SiO2 adsorbent functionalized with 50% by weight amine (28% TEPA and 22% DEA). Variations in CO2 adsorption over time, the influence of adsorbent quantity on adsorption capacity, the affinity of the adsorbent for N2 adsorption, and the adsorption-desorption cycle were investigated. The 28%TEPA-22%DEA-SiO2 adsorbent emerged as the optimal choice due to its large total volume and average pore diameter, absence of a template in its structure, excellent performance in CO2 adsorption, lack of affinity for N2, and robust adsorption-desorption stability.