• Book : 217()
• Pub. Date : 2025
• Page : pp.111253-111253
• Keyword :

Abstract Breast cancer has been recorded as the second leading type of cancer with 2.3 million new cases and 670 000 deaths in 2022. Over time conventional breast cancer treatments such as surgery, radiation therapy, chemotherapy, and hormone therapy, have become less effective due to severe side effects and multidrug resistance. Adopting a complementary and/or alternative treatment strategy can be a significant solution to overcome such limitations. Exploring the potential of an alternative treatment modality like Photodynamic Therapy (PDT) in using naturally derived photosensitizers (PSs) can prove to be a promising anticancer strategy against breast cancer. Several natural products have been used in traditional medicine throughout history for different ailments with success. The diversity of plants, their beneficial primary and secondary phytocompounds make them advantageous as cost-effective cancer treatment strategy with minimal induced side effects. This study aims to demonstrate the phototoxic potential of naturally derived photosensitizers (PS) pheophorbide-a and hypericin to treat MCF-7 breast cancer cells. Hypericin and pheophorbide-a mediated PDT at 0.01 – 0.2 and 0.1 – 1.2 μM at 1 J/cm2 fluency with 595 nm and 660 nm laser irradiation used to treat MCF-7 cells. Post treatment cellular responses were evaluated using 3-(4,5-dimethyl-2- thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, morphological analysis, and flow cytometry (Annexin V/PI). Results showed that both PSs showed significant phototoxic effects on MCF-7 cells via induction of apoptosis and further in vivo investigation is a viable option.

• Book : 2970(1)
• Pub. Date : 2025
• Page : pp.012013-012013
• Keyword :

The Crilin calorimeter is a semi-homogeneous calorimetric system that uses Lead Fluoride (PbF2) crystals with UV-extended Silicon Photomultipliers (SiPMs). Proposed for the Muon Collider, it requires high granularity to distinguish signal particles and address substructures for jet identification. Anticipating substantial occupancy due to beam-induced backgrounds, simulations indicate a photon flux with an average energy of 1.7 MeV and approximately 4.5 MHz/cm2 fluence rate. Prioritizing time-of-arrival measurements within the calorimeter is crucial for associating clusters with interaction vertices. The calorimeter’s energy resolution is vital for determining jet kinematics. Extensive radiation hardness studies confirm the system’s effectiveness when operating in a challenging radiation environment, with exposure up to 10 kGy/year total ionizing dose (TID) and a neutron fluence equivalent to 1014 neutrons 1 MeV/cm2/year. Prototype (Proto-1), with two layers of 3×3 PbF2 crystals, achieved a timing resolution below 50 ps for energy deposits exceeding 1 GeV during 2023 tests. A comprehensive overview, including mechanics, electronics, and test beam outcomes, is presented. Construction is underway for a larger 9 9 crystal matrix prototype with 5 layers, to be completed in 2024. Testing is scheduled for the summer of 2025.

• Book : 320()
• Pub. Date : 2025
• Page : pp.00023-00023
• Keyword :

AbstractCapparisL. (Capparaceae) is a genus of approximately 145 species, many of which have an ancient history of human use. Australia harbours 21 accepted species ofCapparis, including the widespread and taxonomically complexCapparis spinosaL., two phrase-named species, and two putative new species; however, the relationships of these species and their taxonomic status remains to be tested. Here, we present the first phylogenetic trees containing all species of AustralianCapparisbased on the nuclear Angiosperms353 loci. Paralogous gene sequences were identified and handled through ASTRAL-Pro and orthology inference to estimate three species trees using coalescent and concatenated approaches. Phylogenetic discordance was characterised and investigated with a whole-genome duplication analysis. All three trees resolveCapparisas monophyletic and indicate that a whole-genome duplication event occurred in the ancestor of all AustralianCapparisspecies.Capparissect.CapparisandC.sect.Busbeckea(Endl.) Hook.f. are monophyletic, butC. sect.MonostichocalyxRadlk. is non-monophyletic. We infer thatCapparislikely expanded its range to Australia multiple times, resulting in markedly different patterns of diversification and evolution in different clades. The relationships of species within sect.Busbeckeadiffer across trees and are generally poorly supported presumably due to rapid radiation following a second whole-genome duplication event. The relationships of taxa within sect.Capparisand the clades of sect.Monostichocalyxare well-supported, with some evidence of incomplete lineage sorting. We find that the three morphotypes ofCapparis spinosasubsp.nummularia(DC.) Fici across northern Australia consistently form three clades, distinct from the closely relatedCapparis spinosasubsp.cordifolia(Lam.) Fici found outside of Australia. Based on this phylogenomic analysis and morphological study, we describe five new species and two new subspecies ofCapparis, bringing the total number of species in Australia to 26. The phrase-named taxaC. sp. Bamaga (V.Scarth-Johnson 1048A) Qld Herbarium andC. sp. Coen (L.S.Smith 11862) Qld Herbarium are formally described asC. xylofructaW.E.Cooper andC. megacarpaW.E.Cooper, respectively, andC. platyangulataW.E.Cooper & Joyce andC. splendidissimaW.E.Cooper are newly described.Capparis loranthifoliavar.bancroftiiC.T.White ex M.Jacobs is raised to species level asC. bancroftii(C.T.White ex M.Jacobs) W.E.Cooper & Joyce.Capparis spinosasubsp.nummulariais split into three subspecies:C. spinosasubsp.minor(Domin) W.E.Cooper & Joyce, distributed in Northern Territory and inland Queensland;C. spinosasubsp.insularisW.E.Cooper & Joyce distributed on islands off northern Queensland, andC. spinosasubsp.nummulariawhich is restricted to Western Australia and the far north west of the Northern Territory. Descriptions and notes on habitat and distribution are included for all new taxa, and an identification key is provided for all AustralianCapparistaxa.

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :

AbstractA large fraction of newly transcribed RNA is degraded in the nucleus, but nuclear mRNA degradation pathways remain largely understudied. The yeast nuclear endonuclease Rnt1 has a well-characterized role in the maturation of many ncRNA precursors. However, the scope and consequence of its function in mRNA degradation pathways is much less defined. Here, we take a whole-transcriptome approach to identify Rnt1 cleavage sites throughout the yeast transcriptome in vivo, at single-nucleotide resolution. We discover previously unknown Rnt1 cleavage sites in many protein-coding regions and find that the sequences and structures necessary for cleavage mirror those required for the cleavage of known targets. We show that the nuclear localization of Rnt1 functions as an additional layer of target selection control and that cleaved mRNAs are likely exported to the cytoplasm to be degraded by Xrn1. Further, we find that several mRNAs rely heavily on Rnt1 for turnover, and strikingly, mutations in one of these targets,YDR514C, suppress the growth defect of aRNT1deletion. This suggests that Rnt1 limits the expression ofYDR514Cto maintain proper cellular homeostasis. This study uncovers a broader target range and function for the well-known RNase III enzyme.

• Book : ()
• Pub. Date : 2025
• Page :
• Keyword :

This study aimed to develop antibacterial hemp fabrics with good washing durability using a facile preparation method compatible with the current technologies of the textile industry. Silver nanoparticles (AgNPs) were synthesized on hemp fabrics using silver nitrate as a precursor (0.5, 1.0, 1.5, 2.0, and 2.5 g/L) and trisodium citrate as a reducing agent. The obtained spherical AgNPs had a mean diameter of 9.4 ± 3.1 nm. The treated fabrics were characterized for their morphological, thermal, tensile, antibacterial, and ultraviolet (UV)‐blocking properties. AgNPs imparted a yellowish‐brown color to the fabrics and enhanced their thermal stability by promoting char residue formation. However, the nanoparticles reduced the tensile strength compared to the untreated fabric. We observed durable antibacterial activity in samples showing > 90% bacterial reduction after 30 standardized washings. All AgNP‐treated samples exhibited excellent UV protection properties (UPF rating of 50+). Overall, our study successfully demonstrated a facile finishing of hemp fabrics for protection against bacteria and UV radiation.

• Book : 2025(1)
• Pub. Date : 2025
• Page :
• Keyword :

Background/Objectives: Meningiomas are the most common intracranial tumors. Surgery and radiation therapy are the cornerstones of treatment and no standard of care therapy exists for refractory meningiomas. This manuscript aims to provide a comprehensive review of novel diagnostic and therapeutic approaches against these tumors. Methods: A search for the existing literature on systemic therapies for meningiomas was performed on PubMed and a search for presently accruing clinical trials was performed on ClinicalTrials.gov. Results: Systemic treatments, including chemotherapy, somatostatin analogs, anti-hormone therapy, and anti-angiogenic therapy, have been extensively studied with marginal success. Targeted therapies are actively being studied for the treatment of meningiomas, including focal adhesion kinase (FAK), sonic hedgehog signaling pathway, phosphoinositide-3-kinase (PI3K), and cyclin-dependent kinases (CDK) inhibitors. These driver mutations are present only in a subset of meningiomas. In stark contrast, somatostatin receptor 2 (SSTR2) is ubiquitously expressed in meningiomas and was formerly targeted with somatostatin analogs with modest success. Theranostic SSTR2-targeting via [68Ga]DOTATATE for PET imaging and β-emitting [177Lu]DOTATATE for the treatment of meningiomas are currently under active investigation. Conclusions: A nuanced approach is needed for the treatment of refractory meningiomas. Targeted therapies show promise.

• Book : 13(3)
• Pub. Date : 2025
• Page : pp.659-659
• Keyword :

Abstract Background PARP inhibitors are effective in treating ovarian cancer, especially for BRCA1/2 pathogenic variant carriers and those with HRD (homologous recombination deficiency). Concerns over toxicity and costs have led to the search for predictive biomarkers. We present an updated systematic review, expanding on a previous ESMO review on PARP inhibitor biomarkers. Methods Following ESMO’s 2020 review protocol, we extended our search to March 31, 2023, including PubMed and clinical trial data. We also reviewed the reference lists of review articles. We conducted a meta-analysis using a random-effects model to evaluate hazard ratios and assess the predictive potential of biomarkers and the effectiveness of PARP inhibitors in survival. Results We found 375 articles, 103 of which were included after screening (62 primary research, 41 reviews). HRD remained the primary biomarker (95%), particularly BRCA1/2 variants (77%). In the non-HRD category, six articles (10%) introduced innovative biomarkers, including ADP-ribosylation, HOXA9 promoter methylation, patient-derived organoids, KELIM, and SLFN11. Discussion Prospective assessment of real-time homologous recombination repair via nuclear RAD51 levels shows promise but needs validation. Emerging biomarkers like ADP-ribosylation, HOXA9 promoter methylation, patient-derived organoids, KELIM, and SLFN11 offer potential but require large-scale validation.

• Book : 3(1)
• Pub. Date : 2025
• Page :
• Keyword :

The metabolic enzyme aldehyde dehydrogenase 1A1 (ALDH1A1), a cancer stem cell marker associated with poor outcomes in breast cancer, has emerged as a promising therapeutic target in TNBC. The aim of this study was to investigate the role of ALDH1A1 in radiation resistance and redox stress in triple negative breast cancer (TNBC). Functional knockouts of ALDH1A1 were generated by the CRISPR/Cas9-mediated deletion of ALDH1A1 in the SUM159 cell line, and three distinct clonal populations were isolated. Genetic targeting was confirmed by Sanger sequencing, and the loss of ALDH1A1 protein expression was validated by Western blotting. Functional assays assessed ALDEFLUOR activity, cell viability, self-renewal capacity, and reactive oxygen species (ROS) levels with or without radiation in both the bulk population and clonal lines. Interestingly, ALDEFLUOR activity was uniformly lost across all clonal lines; however, functional effects of ALDH1A1 loss on redox stress, survival, and radiation sensitivity were observed in only one clonal population. These findings highlight significant variability in the role of ALDH1A1 among clonal populations, reflecting the complexity of tumor heterogeneity. This underscores the importance of accounting for tumor heterogeneity when targeting ALDH1A1, as certain TNBC subpopulations may rely more heavily on ALDH1A1 function. These insights are critical for developing effective ALDH1A1-targeted therapies.

• Book : 26(5)
• Pub. Date : 2025
• Page : pp.2303-2303
• Keyword :

Abstract Background The aim of this study is to evaluate the induction of DNA damage by 45 radionuclides, including those used in medical applications and others relevant to radiation protection. The research focuses on understanding the differential effects of irradiating lymphocytes with beta/gamma- and alpha-emitting radionuclides using Monte Carlo simulations. A validated Monte Carlo simulation model was used to assess radiation-induced DNA damage in lymphocytes. The model integrates GATE for macroscopic radiation transport and Geant4-DNA for microscopic simulations at the cellular level. For the study, 45 radionuclides were selected and their S-values and DNA double-strand break (DSB) induction were investigated. For beta- and gamma-emitting radionuclides, DSBs per cell per mGy were quantified, while for alpha-emitters, alpha tracks per cell per mGy, DSBs per cell per mGy, and DSBs per micrometer of alpha track were calculated. Result For beta/gamma emitters, the lowest number of DSBs was observed with 125I at 0.006 ± 0.003 DSBs·cell⁻¹·mGy⁻¹, while 99mTc had the highest at approximately 0.015 ± 0.005 DSBs·cell⁻¹·mGy⁻¹. The S-value for lymphocyte nuclei ranked from 0.91 ± 0.14 mGy∙h⁻¹∙MBq⁻¹ (63Ni) and 1.06 ± 0.15 mGy∙h⁻¹∙MBq⁻¹ (125I) to 61.83 ± 1.17 mGy∙h⁻¹∙MBq⁻¹ (90Sr). For alpha-emitting radionuclides, 213Bi produced 0.0677 ± 0.0005 DSB·cell⁻¹·mGy⁻¹ while 232Th yielded 0.0914 ± 0.0004 DSB·cell⁻¹·mGy⁻¹. The DSB linear density for alpha tracks ranged from 7.4 ± 0.1 DSBs/µm for 252Cf to 16.8 ± 0.1 DSBs/µm for 232Th. The S-values for lymphocyte nuclei for alpha emitters varied, from 232Th (0.29 ± 0.21 Gy∙h⁻¹∙MBq⁻¹) to 227Th having the highest at 2.22 ± 0.16 Gy∙h⁻¹∙MBq⁻¹, due to cumulative energy deposition. Conclusions Differences were observed in DNA damage induced by beta/gamma- and alpha-emitting radionuclides. High-energy beta emitters induced DSBs similarly to gamma emitters, but with greater fluctuations in low-energy beta and gamma emitters due to heterogeneous energy deposition and varying interaction probabilities at the cellular level. This study highlights that long half-life alpha-emitting radionuclides may cause more extensive DNA damage due to their higher LET. This work provides a comprehensive S-values database for future experimental studies on radiation-induced DNA damage in lymphocytes.

• Book : 15(1)
• Pub. Date : 2025
• Page :
• Keyword :