AbstractThe magnitude of Type I interferon (IFN) mediated innate immune response within the tumor microenvironment (TME) critically influences the effectiveness of radiotherapy. Unfortunately, due to a myriad of resistance mechanisms, the double‐stranded DNA (dsDNA) signals produced by tumor cells postradiotherapy often induce a diminished response from immune cells. Through chemical screening targeting deubiquitinating enzymes, we identified USP1 (Ubiquitin Specific Peptidase 1) inhibitor as an enhancer of post‐radiotherapy dsDNA responses. Mechanistically, within the context of immune‐stimulatory cells in TME, USP1 serves as a suppressor in the stress‐mediated stages of the cGAS (Cyclic GMP‐AMP synthase) ‐STING (Stimulator of interferon genes protein) signaling pathway, specifically affecting the trafficking of STING from endoplasmic reticulum to Golgi apparatus. It is elucidated that SAR1A (Secretion associated Ras related GTPase 1A) requires K27‐linked oligo‐ubiquitination to assemble the STING‐COP‐II (Coat protein II) transport complex for STING trafficking. USP1 counteracts this activation by removing SAR1A ubiquitination, thereby blocking STING trafficking and activation. Consequently, pharmacological USP1 inhibition using ML323 sustains SAR1A ubiquitination and COP‐II complex formation, significantly enhancing STING trafficking and subsequent Type I IFN production. This intervention substantially amplifies radiotherapy‐induced immune activation in the TME, providing a strategic approach to overcome therapeutic resistance and synergize radiotherapy with immunotherapies.

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AbstractAqueous metal‐selenium batteries based on chalcogenide cathodes, despite their multi‐electron conversion‐type redox reactions and rapid kinetics, suffer from short lifespans and unclear capacity degradation mechanisms. The interfacial interactions between doped carbon and chalcogenides correlate closely with the electrochemical structural evolution. Hence, flower‐like Cu2−xSe wrapped with ultrathin N‐doped carbon layer (Cu2−xSe@N‐C) is synthesized via a simple γ radiation‐pyrolysis route for the first time. The Cu2−xSe@N‐C cathode displays a high‐rate performance and long‐term stability, with a respective capacity of 310.6 mAh g−1 at 20 A g−1 and a capacity retention rate of 92.9% after 30 000 cycles over 2000 h at 5 A g−1. Ex situ X‐ray diffraction and X‐ray photoelectron spectroscopy confirm the reversible Cu storage mechanism of the Cu2−xSe@N‐C cathode and the issues of volume expansion and oxidative dissolution related to the capacity degradation of the Cu2−xSe cathode. Furthermore, X‐ray absorption analysis and theoretical calculations reveal the presence of Se─C interactions between the ultrathin N‐doped carbon and Cu2−xSe. As a result, the physical and chemical dual‐protection of N‐doped carbon via Se‐C not only effectively stabilizes the structural evolution of Cu2−xSe but also endows it with faster electrode reaction kinetics.

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Background: The growing prevalence of skin cancer worldwide can be understood as the result of increased exposure to ultraviolet radiation. Fitzpatrick skin type 1 and 2  are at higher risk. They are poorly studied in Asians. Skin cancers accounts for 20%-30% of neoplasms in Caucasians and 2%-4% in Asians. Three million cases of non-melanoma skin cancer and 132 thousand melanomas are diagnosed worldwide every year. The aim of the study is to study the profile of patients with premalignant and malignant skin lesions visiting the dermatology OPD in Puducherry for a period of 3 years. Methods: Case records of 57,316 patients were studied. 82 case records of premalignant and malignant skin lesions were reviewed and analysed using SPSS software. The prevalence was calculated and also their distribution among age, gender and race was analysed. Results: 82 cases with 93 premalignant and malignant skin lesions were recorded. 77.4% (n=72) were premalignant lesions and 22.5% (n=21) were malignant lesions. The commonest premalignant lesion was leukoplakia (n=38, 52.78%) followed by actinic Keratosis (n=31, 43.05%), keratoacanthoma (n=2, 2.78%) and Bowens disease (n=1, 1.39%). The commonest malignant tumor in the study was basal cell carcinoma (n=12, 57.14%), followed by squamous cell carcinoma (n=9, 42.86%). There were no melanomas or lymphomas reported during the study period. Conclusions: The index of suspicion for the atypical presentations and earlier identification of the premalignant and malignant skin lesions can aid in the selection of appropriate treatment modality and thereby reducing their associated morbidity and mortality.

• Book : 11(2)
• Pub. Date : 2025
• Page : pp.120-125
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Abstract Background The global establishment of cancer registries has prompted a hunt for innovative medications that destroy cancer but not healthy cells. Researchers are currently searching marine environments for new anticancer drugs. Modern chemotherapy uses numerous compounds of aquatic origin. These substances exhibit cytotoxic characteristics through various methods, including DNA damage, apoptosis induction, and growth suppression of cancerous cells. The discovery and development of novel anticancer agents from abundant marine fish is generating increasing interest. The objective of this present study is to extract and assess the anti-proliferative effect of a crude muscle extract from marine pufferfish on human cancer cell lines. Methods The biochemical constituents, protein profile, and anticancer activities of the prepared crude muscle extract were analysed using standard methods on human cancer cell lines (HT-29, MDA-MB-231, A-549, and AGS). Results The biochemical contents, such as protein (7.19 ± 0.20 mg/mL), lipid (1.56 ± 0.14 mg/mL), and carbohydrate (1.19 ± 0.09 mg/mL), were quantitatively analysed. Native PAGE and SDS-PAGE qualitatively analysed the protein profiles, revealing distinct protein bands with molecular weights ranging from 220 to 14 kDa. The crude muscle extract was screened for its cytotoxicity (vero) and cell viability (HT-29, MDA-MB-231, A-549, and AGS) against human cancer cell lines by the MTT assay method. The nuclear morphological changes of the apoptotic cells were stained using propidium iodide, and the morphological changes associated with apoptosis were assessed using acridine orange/ethidium bromide (AO/EB) fluorescence staining. The intensity of the mitochondrial membrane potential of the treated cells was measured using the Rh-123 stain, and the results of the DNA fragmentation assay showed that the crude muscle extract-treated cells showed DNA damage, which is indicative of apoptosis. Conclusions This preliminary study supports that the crude muscle extract from milk spotted marine pufferfish, C. patoca has strong anticancer properties. This implies potential for the development of more effective anticancer drugs in future. Graphical abstract

• Book : 26(1)
• Pub. Date : 2025
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AbstractBackgroundVery high‐energy electrons (VHEEs) in radiotherapy may offer several potential advantages over conventional electron beams and other techniques, for example, the fact that they can be used at ultra‐high dose rates (UHDRs), therefore enabling FLASH radiotherapy. However, the production of secondary particles at high energies (50–200 MeV) has yet to be studied in detail for this technique currently under development.PurposeThe aim of this work was to examine the secondary dose produced by VHEEs, with particular emphasis on bremsstrahlung photons and neutrons, for two beam delivery systems (double scattering [DS] and pencil beam scanning [PBS]).MethodsThe electron, X‐ray, and neutron doses arising from two beam delivery systems (DS or PBS) were computed using Monte Carlo (MC) simulations in the TOPAS (TOol for PArticle Simulation)/Geant4 toolkit, and a preliminary assessment of the secondary dose for a clinical VHEE treatment was performed using a whole‐body phantom. An evaluation of the secondary dose produced by this preliminary design of a VHEE nozzle set in a clinical proton facility was performed, taking into account realistic PBS or DS nozzle configurations.ResultsThe mean doses received by a patient undergoing DS‐VHEE irradiation were found to be up to 5.3‐fold and 6.8‐fold higher for in‐field or out‐of‐field organs for photons and neutrons, respectively, compared to the PBS‐VHEE plan. The results for the secondary neutron dose in intracranial treatments also demonstrate the characteristic of VHEE compared to proton beams for reducing the out‐of‐field secondary neutron dose. The dose to the public area that could be delivered to meet regulatory limits surrounding a possible treatment room in a proton therapy facility was assessed. A regulatory limit of 0.5 µSv/h would give a restriction of 49 and 83 Gy per patient and per fraction for DS and PBS, respectively.ConclusionsThis work describes a method to simulate and compare secondary radiation doses resulting from scattered, scanned VHEE or proton therapy treatments. The results indicate that a conventionally shielded proton therapy room results in acceptable public doses for a preliminary VHEE design and could be of interest for radiation protection purposes and for similar setups. Other facilities with differing layouts may, however, lead to different conclusions, requiring further studies.

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Chondrosarcomas are common bone sarcomas frequently resistant to radiation and chemotherapy, with high recurrence rates, development of metastatic disease, and death. Fibrosarcomas are soft tissue sarcomas associated with poor outcomes. Translocase of outer mitochondrial membrane receptor 20 (TOMM20) is a mitochondrial receptor protein associated with cancer aggressiveness in many cancer subtypes, but the mechanisms remain poorly understood. Here, we studied the effects of TOMM20 overexpression and downregulation on the redox state, mitochondrial oxidative phosphorylation (OXPHOS), and tumor growth using fibrosarcoma and chondrosarcoma models. TOMM20 overexpression increased OXPHOS, NADH, and NADPH with reduced cellular reactive oxygen species (ROS). TOMM20 induced resistance to apoptosis, including with BCL‐2 and OXPHOS complex IV inhibitors, but with increased sensitivity to an OXPHOS complex I inhibitor. Also, TOMM20 induced cell growth and migration in vitro and promoted tumor growth in vivo. Conversely, knocking down TOMM20 using CRISPR‐Cas9 reduced cancer aggressiveness in vivo in both chondrosarcoma and fibrosarcoma mouse models. In conclusion, TOMM20 is a driver of cancer aggressiveness by OXPHOS, apoptosis resistance, and the maintenance of a reduced state.

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Summary The circumscription of the tribe Vernonieae (Compositae) has been problematic due to the reorganisation of the polyphyletic genus Vernonia and the creation of many small genera. Recent phylogenetic studies have focused on the relationships within Vernonieae but few studies have explored the generic relationships within subtribe Piptocarphinae. Of note, some diagnostic features of Piptocarphinae are not unique to the subtribe and are found in other Vernonieae genera. In this study, we explored the phylogenetic relationships in Piptocarphinae, the genus boundaries in this subtribe and tested the infrageneric affinities of the paleate species, using previously published and newly generated nuclear ITS sequences for 65% of the genera of American Vernonieae. Results agree with previous phylogenetic studies, where nearly all subtribes are seemingly paraphyletic or polyphyletic. Piptocarphinae emerges as polyphyletic and should be reduced to contain only the monophyletic Piptocarpha, whereas Critoniopsis is monophyletic only if Cuatrecasanthus is included. We propose placing Cuatrecasanthus and Joseanthus in synonymy of Critoniopsis, resulting in eight new combinations: C. chimborazensis, C. giannasii, C. flexipappa, C. kingii, C. lanceolatus, C. sandemanii, C. sparrei and C. trichotoma and a new name, C. boekei. Piptocoma also resolves as non-monophyletic but no taxonomic recommendations are made, as few species have been sampled in phylogenies so far. We present a new combination in the genus Piptocarpha, P. glomerulata. The presence of paleae likely emerged independently at least three times in American Vernonieae. Paleate receptacles are present in three different series in Piptocarpha subg. Piptocarpha, which indicates that paleae have likely arisen twice in the evolution of Piptocarpha. Finally, a brief discussion about the adaptive function of paleae and pappus is provided. 

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