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The effects of exposure to ultraviolet radiation (UVR), 280-400 nm, in different life histories and development stages of the kelps, Lessonia nigrescens and L. trabeculata, collected in the south-east Pacific coast (30[degrees]S) were evaluated in the laboratory. Germination and viability (motile zoospores, settled spores), diameter of the primary cell of the gametophytes, percentage of female gametophytes, fertility and sporophytes production were measured after exposure to three radiation treatments (PAR; PAR + UVA; PAR + UVA + UVB). The effects of UVR in young sporophytes (diploid stage) were evaluated as changes in maximal quantum yield of chlorophyll fluorescence of photosystem II (PSII) ([F.sub.v]/[F.sub.m]). A significant decrease in all variables was observed for the treatment that included UVB (PAR + UVA + UVB) after 2 and 4 h of exposure, in relation to the control. The motile spores were more sensitive to UVR exposure compared to settled spores and gametophytes, suggesting that along with an increase in ontogenetic development; there is an increase in the tolerance to UVR. In addition, it was observed that early stages of the intertidal L. nigrescens were more tolerant to UVR compared to the subtidal L. trabeculata. These results allow initially to infer that UVR may be regarded as an important environmental factor influencing the upper limit of distribution of these species, mainly through its detrimental effects on the early stages of the life cycle., Introduction Early developmental stages of kelps (zoospores, gametophytes and small sporophytes) are shade-adapted organisms in contrast to adult thalli (sporophytes) (Kain 1964; Gomez and Wiencke 1996; Dring et al. 1996). [...]

Cell surface molecules transiently upregulated on activated T cells can play a counter-regulatory role by inhibiting T cell function. Deletion or blockade of such immune checkpoint receptors has been investigated to improve the function of engineered immune effector cells. CD38 is upregulated on activated T cells, and although there have been studies showing that CD38 can play an inhibitory role in T cells, how it does so has not fully been elucidated. In comparison with molecules such as PD1, CTLA4, LAG3, and TIM3, we found that CD38 displays more sustained and intense expression following acute activation. After deleting CD38 from human chimeric antigen receptor (CAR) T cells, we showed relative resistance to exhaustion in vitro and improved anti-tumor function in vivo . CD38 is a multifunctional ectoenzyme with hydrolase and cyclase activities. Reintroduction of CD38 mutants into T cells lacking CD38 provided further evidence supporting the understanding that CD38 plays a crucial role in producing the immunosuppressive metabolite adenosine and utilizing nicotinamide adenine dinucleotide (NAD) in human T cells. Taken together, these results highlight a role for CD38 as an immunometabolic checkpoint in T cells and lead us to propose CD38 deletion as an additional avenue for boosting CAR T cell function., Competing Interests: S.G. has patents related to CAR therapy with royalties paid from Novartis to the University of Pennsylvania. S.G. is a scientific cofounder and holds equity in Interius Biotherapeutics and Carisma Therapeutics. S.G. is a scientific advisor to Carisma, Cartography, Currus, Interius, Kite, NKILT, Mission Bio, and Vor Bio., (© 2024 The Author(s).)

Many hematologic malignancies are not curable with chemotherapy and require novel therapeutic approaches. Chimeric antigen receptor (CAR) T-cell therapy is 1 such approach that involves the transfer of T cells engineered to express CARs for a specific cell-surface antigen. CD38 is a validated tumor antigen in multiple myeloma (MM) and T-cell acute lymphoblastic leukemia (T-ALL) and is also overexpressed in acute myeloid leukemia (AML). Here, we developed human CD38-redirected T cells (CART-38) as a unified approach to treat 3 different hematologic malignancies that occur across the pediatric-to-adult age spectrum. Importantly, CD38 expression on activated T cells did not impair CART-38 cells expansion or in vitro function. In xenografted mice, CART-38 mediated the rejection of AML, T-ALL, and MM cell lines and primary samples and prolonged survival. In a xenograft model of normal human hematopoiesis, CART-38 resulted in the expected reduction of hematopoietic progenitors, which warrants caution and careful monitoring of this potential toxicity when translating this new immunotherapy into the clinic. Deploying CART-38 against multiple CD38-expressing malignancies is significant because it expands the potential for this novel therapy to affect diverse patient populations., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Ecuador is one of the largest banana exporters in the world. This sector generates wealth and employment in the country. Life cycle method tools support finding critical points and improvement measures in systems. In this study, the Ecuadorian banana is evaluated through life cycle assessment (LCA), including agriculture, packaging, transfer to the Port of Guayaquil, and transport to a foreign port. OpenLCA software was used, applying the Recipe Midpoint (H) V1.13 impact evaluation method and using primary data collected from a local producer and secondary data from Ecoinvent 3.6 databases, Agribalyse 3.0.1, and the literature. Functional units were established at three levels: "1 ton of Banana at-the-farm-gate"; "1 ton of Banana at-the-packaging-stage-gate"; and "1 ton of Banana at-the-port-of-destination". The impact categories evaluated are climate change (GWP100), fossil depletion (FDP), freshwater eutrophication (FEP), marine eutrophication (MEP), ozone layer depletion (ODPinf), particulate matter formation (PMFP), formation of photochemical oxidants (POFP), and terrestrial acidification (TAP100). The carbon footprint (GWP100) of "Banana at-the-farm-gate", "Banana at-the-packaging-stage-gate", and "Banana at-the-foreign-port" ranged from 194 to 220, 342 to 352, and 615.41 to 625.44 kg CO 2 -Eq/Ton banana, respectively. Hotspots of the system are the fertilizer field emissions, cardboard packaging, rachis disposal, and maritime transport. Improvement measures should focus on reducing the amount of fertilizers and developing circular alternatives for residual biomass valorization.

T cells undergo activation, maturation, and differentiation in which they can substantially transform and restructure. This includes metabolic adaptations which have been well recognized to be specific for T cell subsets. T cell subset-specific metabolism is thought to reflect different bioenergetic requirements as well as adaptations to environmental conditions in which the T cells operate. The metabolic changes that occur in T cells are orchestrated by signaling cascades that lead to rapid post-translational changes and through transcription factors which facilitate more long-term adaptations. In addition, metabolites produced within T cells or taken up from the environment can influence gene expression by altering chromatin accessibility or the effectiveness of transcription factors through post-translational modifications, and thus act as transcription regulators in their own right., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (a novel coronavirus), which was first identified amid an outbreak of respiratory illness cases in Wuhan, China and declared a global health emergency, is currently considered an additional challenge in the management of patients with breast cancer (BC). Cancer patients are more vulnerable to becoming infected with severe acute respiratory syndrome coronavirus 2 and are more likely to suffer additional complications that can increase mortality. Identifying those BC patients who require more urgent therapy than others in the current situation is essential. These recommendations are based on and have been adapted from those similarly published by international scientific societies for BC management. They are divided mainly by clinical stage (early, advanced), subtype [luminal, human epidermal growth factor receptor 2 (HER2), triple-negative], or type of medical treatment and setting (neoadjuvant, adjuvant, metastatic). Recommendations for HER2 and triple-negative subtypes are similar, whereas in luminal subtype there are various options of management. The objective is to adapt guidelines to local context through relevant decision-makers, avoiding duplication of efforts and optimizing use or resources. We hope that these recommendations will help medical oncologists provide the best quality care to BC patients during the COVID-19 pandemic with information tailored to our healthcare system., Aim: To establish and adapt recommendations from those published by international scientific societies for BC management., Methods: The Peruvian Society of Medical Oncology developed a consensus and propose here a manuscript with recommendations for oncological medical treatment of BC during the COVID-19 pandemic. The Peruvian Society of Medical Oncology invited a panel of experts and opinion leaders on BC working in major health care systems around Peru. Panel experts selected three international clinical practice guidelines (National Comprehensive Cancer Network, European Society for Medical Oncology, Spanish Foundation Research Group in Breast Cancer), considering that these are more representative in COVID-19 management. Also, the panel agreed to include at least one European and American clinical practice guideline., Results: Recommendations about BC management during the COVID-19 pandemic were divided mainly by clinical stage (early, advanced), subtype (luminal, HER2, triple-negative), or type of medical treatment and setting (neoadjuvant, adjuvant, metastatic). Recommendations for HER2 and triple-negative subtypes were similar between clinical practice guidelines, whereas in luminal subtype there were various options of management. One hundred twelve recommendations were reviewed, adapted, and voted. A consensus was made in order to provide best decisions of management, avoid duplication of efforts, and optimize medical resources, considering health care system reality. These recommendations are not intended to replace clinical judgment., Conclusion: Most of recommendations are similar, mainly in high-risk subtypes (HER2, triple-negative). Certain societies adapt them to deal with different situations involving the best decision in the management of BC patients., Competing Interests: Conflict-of-interest statement: Authors declare no conflict of interests for this article., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Chimeric antigen receptor (CAR) T cell therapy has shown promise in hematologic malignancies, but its application to solid tumors has been challenging 1-4 . Given the unique effector functions of macrophages and their capacity to penetrate tumors 5 , we genetically engineered human macrophages with CARs to direct their phagocytic activity against tumors. We found that a chimeric adenoviral vector overcame the inherent resistance of primary human macrophages to genetic manipulation and imparted a sustained pro-inflammatory (M1) phenotype. CAR macrophages (CAR-Ms) demonstrated antigen-specific phagocytosis and tumor clearance in vitro. In two solid tumor xenograft mouse models, a single infusion of human CAR-Ms decreased tumor burden and prolonged overall survival. Characterization of CAR-M activity showed that CAR-Ms expressed pro-inflammatory cytokines and chemokines, converted bystander M2 macrophages to M1, upregulated antigen presentation machinery, recruited and presented antigen to T cells and resisted the effects of immunosuppressive cytokines. In humanized mouse models, CAR-Ms were further shown to induce a pro-inflammatory tumor microenvironment and boost anti-tumor T cell activity.

Rationale: Mechanical forces are transduced to nuclear responses via the linkers of the nucleoskeleton and cytoskeleton (LINC) complex, which couples the cytoskeleton to the nuclear lamina and associated chromatin. While disruption of the LINC complex can cause cardiomyopathy, the relevant interactions that bridge the nucleoskeleton to cytoskeleton are poorly understood in the cardiomyocyte, where cytoskeletal organization is unique. Furthermore, while microtubules and desmin intermediate filaments associate closely with cardiomyocyte nuclei, the importance of these interactions is unknown. Objective: Here, we sought to determine how cytoskeletal interactions with the LINC complex regulate nuclear homeostasis in the cardiomyocyte. Methods and Results: To this end, we acutely disrupted the LINC complex, microtubules, actin, and intermediate filaments and assessed the consequences on nuclear morphology and genome organization in rat ventricular cardiomyocytes via a combination of super-resolution imaging, biophysical, and genomic approaches. We find that a balance of dynamic microtubules and desmin intermediate filaments is required to maintain nuclear shape and the fidelity of the nuclear envelope and lamina. Upon depletion of desmin (or nesprin [nuclear envelope spectrin repeat protein]-3, its binding partner in the LINC complex), polymerizing microtubules collapse the nucleus and drive infolding of the nuclear membrane. This results in DNA damage, a loss of genome organization, and broad transcriptional changes. The collapse in nuclear integrity is concomitant with compromised contractile function and may contribute to the pathophysiological changes observed in desmin-related myopathies. Conclusions: Disrupting the tethering of desmin to the nucleus results in a loss of nuclear homeostasis and rapid alterations to cardiomyocyte function. Our data suggest that a balance of forces imposed by intermediate filaments and microtubules is required to maintain nuclear structure and genome organization in the cardiomyocyte.

NF-κB-inducing kinase (NIK) mediates non-canonical NF-κB signaling downstream of multiple TNF family members, including BAFF, TWEAK, CD40, and OX40, which are implicated in the pathogenesis of systemic lupus erythematosus (SLE). Here, we show that experimental lupus in NZB/W F1 mice can be treated with a highly selective and potent NIK small molecule inhibitor. Both in vitro as well as in vivo, NIK inhibition recapitulates the pharmacological effects of BAFF blockade, which is clinically efficacious in SLE. Furthermore, NIK inhibition also affects T cell parameters in the spleen and proinflammatory gene expression in the kidney, which may be attributable to inhibition of OX40 and TWEAK signaling, respectively. As a consequence, NIK inhibition results in improved survival, reduced renal pathology, and lower proteinuria scores. Collectively, our data suggest that NIK inhibition is a potential therapeutic approach for SLE.