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.

Toward a numerically efficient description of bulk-solvated anionic states.

We investigate the vertical electron attachment energy (VAE) of 1-methyl-4-nitroimidazole, a model radiosensitizer, employing quantum mechanics/molecular mechanics (QM/MM) and QM/polarized continuum (QM/PCM) solvation models. We considered the solvent-excluded surface (QM/PCM-SES) and Van der Waals (QM/PCM-VDW) cavities within the PCM framework, the electrostatic embedding QM/MM (EE-QM/MM) model, and the self-consistent sequential QM/MM polarizable electrostatic embedding (scPEE-S-QM/MM) model. Due to slow VAE convergence concerning the number of QM solvent molecules, full QM calculations prove inefficient. Ensemble averages in these calculations do not align with VAEs computed for the representative solute-solvent configuration. QM/MM and QM/PCM calculations show agreement with each other for sufficiently large QM regions, although the QM/PCM-VDW model exhibits artifacts linked to the cavity. QM/MM models demonstrate good agreement between ensemble averages and VAEs calculated with the representative configuration. Notably, the VAE computed with the scPEE-S-QM/MM model achieves faster convergence concerning the number of QM water molecules compared to the EE-QM/MM model, attributed to enhanced efficiency from MM charge polarization in the scPEE-S-QM/MM approach. This emphasizes the importance of QM/classical models with accurate solute-solvent and solvent-solvent mutual polarization for obtaining converged VAEs at a reasonable computational cost. The full-QM approach is very inefficient, while the microsolvation model is inaccurate. Computational savings in QM/MM models result from electrostatic embedding and the representative configuration, with the scPEE-S-QM/MM approach emerging as an efficient tool for describing bulk-solvated anions within the QM/MM framework. Its potential extends to improving transient anion state descriptions in biomolecules and radiosensitizers, especially given the frequent employment of microsolvation models.

Alternative to antimicrobial growth promoters in the diets of broilers challenged with subclinical necrotic enteritis.

Necrotic enteritis (NE) is a disease of worldwide distribution, which affects young broilers and causes economic losses on a scale of 6 billion dollars per year. For decades, NE was controlled in poultry flocks by dietary administration of low doses of antimicrobial growth promoters (AGPs). However, an increase in NE incidence was noted after the AGP ban. This study aimed to compare the effect of an antibiotic (Enramycin) diet to a combination of sodium butyrate, hydrolyzed yeast, and zinc proteinate (ViligenTM) on broiler diets regarding performance, blood parameters, intestinal permeability, morphology and lesions, and carcass yield of broilers challenged with Eimeria spp. and Clostridium perfringens to simulate subclinical necrotic enteritis. A total of 1,150 one-day-old male broiler chickens with an initial average weight of 43.9 ± 0.65 g were allocated to 50 experimental pens. Animals were divided into 5 groups: Negative control (NC) without additives; Positive control (PC) with 0.12 g/ton of Enramycin (8%); V500, V1000, and V1500 with the addition of 500, 1.000, and 1.500 g/ton of Viligen, respectively. All animals were challenged by Eimeria spp. at 7 d of age and by C. perfringens at 17, 18, and 19 d for induction of subclinical NE. The broilers fed with all concentrations of Viligen showed similar performance, blood parameters, intestinal permeability, and carcass yield compared to PC broilers. However, NC broilers showed higher FCR compared to PC broilers from 1 to 33 d (1.42 vs. 1.39) (P = 0.048) and from 1 to 42 d (1.51 vs. 1.49) (P < 0.001). V1500 broilers had fewer intestinal lesions at 28 d when compared to the PC treatment (P < 0.05) and showed that higher Viligen inclusion resulted in lower intestinal damage. At 21 d, the V500 group showed higher intestinal morphology characteristics (VH:VD 4.9 vs. 3.5) compared to the PC treatment (P < 0.001). Thus, in this study, the dietary addition of Viligen to broilers challenged by an experimental model of subclinical NE resulted in lower intestinal damage and similar performance to that obtained by the addition of Enramycin.

Effects of high-definition transcranial direct current stimulation combined with inspiratory muscle training for treating respiratory sequelae of long COVID: A case series.

INTRODUCTION: Long COVID occurs when numerous symptoms begin 3 weeks after acute infection and last for 12 months or more. High-definition transcranial direct current stimulation (HD-tDCS) has been tested in patients with COVID-19; however, previous studies did not investigate the HD-tDCS use combined with inspiratory muscle training (IMT) for respiratory sequelae of long COVID. CASE PRESENTATION: Six individuals (four women and two men) aged between 29 and 71 years and presenting with respiratory sequelae of long COVID were included. They were submitted to an intervention that comprised HD-tDCS combined with IMT twice a week for 5 weeks. Lung function and respiratory muscle assessments were performed at baseline and after 5 weeks of intervention. IMPLICATIONS ON PHYSIOTHERAPY PRACTICE: HD-tDCS may enhance the IMT effects by increasing respiratory muscle strength, efficiency, and lung function of individuals with long COVID.

Novel Approach for Predicting Vertical Electron Attachment Energies in Bulk-Solvated Molecules.

When low-energy electrons interact with molecules, they can give rise to transient anion states commonly known as resonances. These states are formed through vertical electron attachment processes and have the potential to induce various forms of DNA lesions, including base damage, single- and double-strand breaks, cross-links, and clustered lesions that are challenging to repair. So far, most experimental and theoretical studies have investigated the formation of resonances of (bio)molecules in the gas phase or in microsolvated environments. Since cellular environments are mainly composed of water molecules, it is crucial to understand how bulk water affects the resonances of (bio)molecules. Given the existing gap in studies on resonances of bulk-solvated molecules, we propose a novel theoretical-computational approach to address this void. Our approach combines the multibasis-set (time-dependent-)density functional theory and self-consistent sequential quantum mechanics/molecular mechanics polarizable electrostatic embedding methods. We apply this combined methodology to predict the vertical electron attachment energies of 1-methyl-5-nitroimidazole (1M5NI), a well-known radiosensitizer model, in bulk water. In addition, we analyze the rapid mutual polarization between the resonances (both shape- and core-excited) of 1M5NI and the surrounding bulk water environment. For comparison, we also studied the isolated and microsolvated 1M5NI. Overall, while the polarization of the environment is clearly sensitive to the solute charge, causing a significant impact on the vertical electron affinity and consequently on the attachment electron energies, it does not have a significant impact on the excitation energies of the anion.

Excited state properties of an A-D-A non-fullerene electron acceptor: a LC-TD-DFTB study.

Understanding charge transfer processes is essential to estimate the performance of organic photovoltaic technologies. Although experimental production is on the rise, predictability strongly relies on theoretical modeling, which is limited to the size of semiconductors. As a computationally favorable approach, we benchmarked the long-range corrected (LC) time-dependent (TD) formulation of the semi-empirical density functional-based tight-binding method (DFTB) for three polycyclic aromatic hydrocarbons (PAHs) and studied the DTP-IC-4Ph molecule, a PAH-based non-fullerene electron acceptor (NFA) with an A-D-A backbone structure. After a thorough investigation into the long-range parameter (ω) tuning for naphthalene, anthracene and pyrene, the excitation energies, oscillator strengths and Natural Transition Orbitals (NTOs) were compared with the standard ωB97X-D/6-31G(d,p) level of theory and the ADC2/6-31G(d,p) multiconfigurational method. We estimated mobility-related properties of the NFA and considered 1000 thermally accessible configurations to qualitatively reproduce the experimental absorption profile and investigate the energetic disorder. Finally, we conducted a fragment-based analysis using the one-electron transition density matrix (1TDM) to determine the character of the excited states and investigate the effect of side chains on exciton formation. Our results are sensitive to the level of theory and highly dependent on the long-range parameter but suggest that the presence of alkyl chains promotes a higher average charge delocalization and allows for additional hopping mechanisms, favoring the charge transfer dynamics.

2024 Statement from Asia expert operators on transcatheter pulmonary valve replacement.

Transcatheter pulmonary valve replacement (TPVR), also known as percutaneous pulmonary valve implantation, refers to a minimally invasive technique that replaces the pulmonary valve by delivering an artificial pulmonary prosthesis through a catheter into the diseased pulmonary valve under the guidance of X-ray and/or echocardiogram while the heart is still beating not arrested. In recent years, TPVR has achieved remarkable progress in device development, evidence-based medicine proof and clinical experience. To update the knowledge of TPVR in a timely fashion, and according to the latest research and further facilitate the standardized and healthy development of TPVR in Asia, we have updated this consensus statement. After systematical review of the relevant literature with an in-depth analysis of eight main issues, we finally established eight core viewpoints, including indication recommendation, device selection, perioperative evaluation, procedure precautions, and prevention and treatment of complications.

Fragmentation of the DNA Lesion 8-oxo-Guanine by Low-Energy Electrons.

8-oxo-Guanine is a mutagenic lesion produced by reactions involving reactive oxygen species and guanine in DNA. Its production induces mispairing between the canonical nucleobases during DNA replication such that various types of cancers are associated with the DNA lesion. Since radiation therapy is used in some cases, the interaction of low-energy electrons with 8-oxo-guanine can in turn produce other reactive species, which in principle could have either a detrimental or protective effect on the organism. Motivated by these facts, we report a comparative experimental study of electron-induced fragmentation of guanine and 8-oxo-guanine, along with a theoretical study of the π* shape resonances and bound anion states, which may trigger those dissociation reactions. The electron-induced fragmentation of 8-oxo-guanine is remarkably distinct from the native form. More complex reactions were observed for the oxidized species, which may produce several anion fragments at very low energies (∼0 eV). The dehydrogenated parent anion, which is already a minor fragment in guanine, was completely suppressed in 8-oxo-guanine. The calculated thermodynamical thresholds also suggest that NH2 elimination in guanine, at sub-excitation energies, proceeds via a complex reaction involving rearrangement steps.

Trans-mucosal platforms for dental implants: Strategies to induce muco-integration and shield peri-implant diseases.

OBJECTIVES: Trans-mucosal platforms connecting the bone-anchored implants to the prosthetic teeth are essential for the success of oral rehabilitation in implant dentistry. This region promotes a challenging environment for the successfulness of dental components due to the transitional characteristics between soft and hard tissues, the presence of bacteria, and mechanical forces. This review explored the most current approaches to modify trans-mucosal components in terms of macro-design and surface properties. METHODS: This critical review article revised intensely the literature until July 2023 to demonstrate, discuss, and summarize the current knowledge about marketable and innovative trans-mucosal components for dental implants. RESULTS: A large number of dental implant brands have promoted the development of several implant-abutment designs in the clinical market. The progress of abutment designs shows an optimistic reduction of bacteria colonization underlying the implant-abutment gap, although, not completely inhibited. Fundamental and preclinical studies have demonstrated promising outcomes for altered-surface properties targeting antibacterial properties and soft tissue sealing. Nanotopographies, biomimetic coatings, and antibiotic-release properties have been shown to be able to modulate, align, orient soft tissue cells, and induce a reduction in biofilm formation, suggesting superior abilities compared to the current trans-mucosal platforms available on the market. SIGNIFICANCE: Future clinical implant-abutments show the possibility to reduce peri-implant diseases and fortify soft tissue interaction with the implant-substrate, defending the implant system from bacteria invasion. However, the absence of technologies translated to commercial stages reveals the need for findings to "bridge the gap" between scientific evidences published and applied science in the industry.

Could Cesarean Delivery Help Prevent Mother-to-Child Transmission of Human T-Lymphotropic Virus Type 1?

BACKGROUND: Mother-to-child transmission (MTCT) of human T-lymphotropic virus type 1 (HTLV-1) is an important route of transmission that can cause lifelong infection. There is high morbidity and mortality due to adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy (HAM), and other inflammatory disorders. These conditions develop in nearly 10% of people with HTLV-1 infection, with a higher risk if infection occurs early in life. Identification of risk factors can inform targeted measures to reduce HTLV-1 MTCT. This study aimed to investigate the potential of cesarean delivery to prevent HTLV-1 MTCT. METHODS: We performed a review of the cases of women and their offspring under regular follow-up at the HTLV-1 outpatient clinic at the Institute of Infectious Diseases Emilio Ribas. RESULTS: A total of 177 HTLV-1-infected women and 369 adult offspring were investigated. Overall, 15% of the children were positive for HTLV-1 and 85% were negative. Regarding vertical transmission, we found that a breastfeeding duration of >6 months was associated with MTCT. Moreover, maternal proviral load was not associated with transmission, but high educational level and cesarean delivery were identified as protective factors. CONCLUSIONS: HTLV-1 MTCT was associated with mother's age at delivery of >25 years, low educational level, prolonged breastfeeding, and vaginal delivery.

Assessment of eutrophication from phosphorus remobilization after resuspension of coastal sediments from an urban tropical estuary.

Dredging activities cause sediment resuspension, which can change the bioavailability of nutrients such as phosphorus (P) in aquatic ecosystems due to remobilization. This study evaluated the remobilization of P in the solid and dissolved phase before and after sediment resuspension in the Meriti and Iguaçu River estuaries and the Rio de Janeiro and Niterói harbor in Guanabara Bay (Rio de Janeiro, Brazil). Three water and sediment samples were collected at each point. Dissolved phosphorus (DP), total phosphorus (TP), organic phosphorus (OP), and inorganic phosphorus (IP) were analyzed before and after resuspension. Resuspension directly impacted the fine-grained samples, causing the release of P into the water column after resuspension, increasing eutrophication of the estuary and risk to biota. The phosphorus enrichment index (PEI) was calculated in the four areas, and in all areas, the index was above 1, which means high ecological risk. The area with sandy granulometry and a lower percentage of organic matter showed an increase in the index after resuspension. The resuspension may impact the increase of eutrophication in some areas, due to the remobilization of the sediment and the adsorbed contaminants.

Association between the Arg72Pro Genotypes in the TP53 Gene and Ile655Val in the HER2 Gene and the Risk of Developing Breast Cancer in the Population of Amapá, Northern Brazil.

BACKGROUND: The polymorphisms Arg72Pro in the TP53 gene (rs1042522) and Ile655Val in the HER2 gene (rs1136201) have been related to susceptibility to several types of cancer. Different studies show the association of these polymorphisms with breast cancer, so our aim in this study was to investigate whether the Arg72Pro and Ile655Val polymorphisms have any influence on the risk of developing breast cancer in women from the city of Macapá, Amapá, located in the brazilian amazon region. METHODS AND RESULTS: We then analyzed 80 DNA samples from women with breast cancer and 83 DNA samples from women without the disease, by the Restriction Fragment Length Polymorphism - Polymerase Chain Reaction (PCR-RFLP) technique. The genotype frequencies for rs1042522 were Ar/Arg 23.7%, Arg/Pro 47.5% and Pro/Pro 28.5% in patients and in controls Ar/Arg 69.8%, Arg/Pro 19.2% and Pro/Pro 10.8%. For the HER-2 gene the frequency of Ile/Ile, Ile/Val and Val/Val genotypes was 82.5%, 17.5% and 0% in the patients and 75.9%, 20.4% and 3.6% in the controls. The presence of at least one altered allele in rs1042522 and rs1136201 polymorphisms was found in 91.25% of patient samples. CONCLUSION: This study found a significant association between the Arg/Pro and Pro/Pro genotypes in the TP53 gene and the Ile/Val genotype in the HER-2 gene and breast cancer risk, however, we emphasize that more studies need to be carried out in the investigated population to consolidate our results.

Semisynthesis, in silico study and in vitro antibacterial evaluation of fucosterol derivatives.

Thirteen fucosterol derivatives were prepared by structural modification at the hydroxyl group in C-3 and catalytic hydrogenation at the carbon-carbon double bond in C-5(6) and C-24(28). The structures of all compounds were established based on their spectral data (IR, MS, and NMR). Fucosterol (1) and its derivatives (2-12, and a mixture of 13a and 13b) were evaluated for their in vitro antibacterial activity against Klebsiella pneumoniae (ATCC 10031), Escherichia coli (ATCC 10536), Pseudomonas aeruginosa (ATCC 15442), Streptococcus mutans (ATCC 0046) and Staphylococcus aureus using the microdilution method. Among them, 1, 8, 9, 10, and a mixture of 13a and 13b exhibited the best antibacterial activity. The derivative 7 was inactive against all bacterial strains evaluated (MIC ≥ 2.327 mM). In addition, the investigation of binding interactions of more active compounds (1, 8, 9, 10, and mixture of 13a and 13b) to appropriate proteins was performed using molecular docking. This paper registers for the first time the in silico studies on the antibacterial activity of compounds 1, 8, 9, 10, and mixture of 13a/13b, and the spectral data of compounds 4, 6, and 7.

Parent anion radical formation in coenzyme Q0: Breaking ubiquinone family rules.

We report electron attachment (EA) measurements for the parent anion radical formation from coenzyme Q0 (CoQ0) at low electron energies (<2 eV) along with quantum chemical calculations. CoQ0 may be considered a prototype for the electron withdrawing properties of the larger CoQ n molecules, in particular ubiquinone (CoQ10), an electron carrier in aerobic cell respiration. Herein, we show that the mechanisms for the parent anion radical formation of CoQ0 and CoQ n (n = 1,2,4) are remarkably distinct. Reported EA data for CoQ1, CoQ2, CoQ4 and para-benzoquinone indicated stabilization of the parent anion radicals around 1.2-1.4 eV. In contrast, we observe for the yield of the parent anion radical of CoQ0 a sharp peak at âˆ¼ 0 eV, a shoulder at 0.07 eV and a peak around 0.49 eV. Although the mechanisms for the latter feature remain unclear, our calculations suggest that a dipole bound state (DBS) would account for the lower energy signals. Additionally, the isoprenoid side chains in CoQ n (n = 1,2,4) molecules seem to influence the DBS formation for these compounds. In contrast, the side chains enhance the parent anion radical stabilization around 1.4 eV. The absence of parent anion radical formation around 1.4 eV for CoQ0 can be attributed to the short auto-ionization lifetimes. The present results shed light on the underappreciated role played by the side chains in the stabilization of the parent anion radical. The isoprenoid tails should be viewed as co-responsible for the electron-accepting properties of ubiquinone, not mere spectators of electron transfer reactions.

The three-center two-positron bond.

Computational studies have shown that one or more positrons can stabilize two repelling atomic anions through the formation of two-center positronic bonds. In the present work, we study the energetic stability of a system containing two positrons and three hydride anions, namely 2e+[H3 3-]. To this aim, we performed a preliminary scan of the potential energy surface of the system with both electrons and positrons in a spin singlet state, with a multi-component MP2 method, that was further refined with variational and diffusion Monte Carlo calculations, and confirmed an equilibrium geometry with D 3h symmetry. The local stability of 2e+[H3 3-] is demonstrated by analyzing the vertical detachment and adiabatic energy dissociation channels. Bonding properties of the positronic compound, such as the equilibrium interatomic distances, force constants, dissociation energies, and bonding densities are compared with those of the purely electronic H3 + and Li3 + systems. Through this analysis, we find compelling similarities between the 2e+[H3 3-] compound and the trilithium cation. Our results strongly point out the formation of a non-electronic three-center two-positron bond, analogous to the well-known three-center two-electron counterparts, which is fundamentally distinct from the two-center two-positron bond [D. Bressanini, J. Chem. Phys., 2021, 155, 054306], thus extending the concept of positron bonded molecules.

Low-Energy Electron Interactions with Resveratrol and Resorcinol: Anion States and Likely Dissociation Pathways.

We report a computational study of the anion states of the resveratrol (RV) and resorcinol (RS) molecules, also investigating dissociative electron attachment (DEA) pathways. RV has well-known beneficial effects in human health, and its antioxidant activity was previously associated with DEA reactions producing H2. Our calculations indicate a valence bound state (π1*) and four resonances (π2* to π5*) for that system. While the computed thermodynamic thresholds are compatible with DEA reactions producing H2 at 0 eV, the well-known mechanism involving vibrational Feshbach resonances built on a dipole bound state should not be present in RV. Our results suggest that the shallow π1* valence bound state is expected to account for H2 elimination, probably involving π1*/σOH* couplings along the vibration dynamics. The RS molecule is also an oxidant and a subunit of RV. Because two close-lying hydroxyl groups are found in the RS moiety, the H2-elimination reaction in RV should take place at the RS site. Our calculations point out a correspondence between the anion states of RV and RS and even between the thresholds. Nevertheless, the absence of bound anion states in RS, indicated by our calculations, is expected to suppress the H2-formation channel at 0 eV. One is led to conclude that the ethene and phenol subunits in RV stabilize the π1* state, thus switching on the DEA mechanism producing H2.

UPLC-HDMSE to discover serum biomarkers in adults with type 1 diabetes.

Type 1 diabetes (T1D) is a complex disease with metabolic and functional changes that can alter an individual's proteome. An LC-MS/MS analytical method, in an HDMSE system, was used to identify differentially expressed proteins in the high abundance protein-depleted serum of T1D patients and healthy controls. Samples were processed in Progenesis QI for Proteomics software. A functional enrichment of the proteins was performed with Gene Ontology and ToppGene, and the interactions were visualized by STRING 11.5. As a result, 139 proteins were identified, 14 of which were downregulated in the serum of patients with T1D compared to controls. Most of the differentially expressed proteins were shown to be involved with the immune system, inflammation, and growth hormone stimulus response, and were associated with the progression of T1D. Differential protein expression data showed for the first-time changes in CPN2 expression levels in the serum of patients with T1D. Our findings indicate that these proteins are targets of interest for future investigations and for validation of protein biomarkers in T1D.