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1.
Gigascience ; 132024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-39101784

RESUMO

BACKGROUND: Venom glands play a key role in the predation and defense strategies of almost all spider groups. However, the spider family Uloboridae lacks venom glands and has evolved an adaptive strategy: they excessively wrap their prey directly with spider silk instead of paralyzing it first with toxins. This shift in survival strategy is very fascinating, but the genetic underpinnings behind it are poorly understood. RESULTS: Spanning multiple spider groups, we conducted multiomics analyses on Octonoba sinensis and described the adaptive evolution of the Uloboridae family at the genome level. We observed the coding genes of myosin and twitchin in muscles are under positive selection, energy metabolism functions are enhanced, and gene families related to tracheal development and tissue mechanical strength are expanded or emerged, all of which are related to the unique anatomical structure and predatory behavior of spiders in the family Uloboridae. In addition, we also scanned the elements that are absent or under relaxed purifying selection, as well as toxin gene homologs in the genomes of 2 species in this family. The results show that the absence of regions and regions under relaxed selection in these spiders' genomes are concentrated in areas related to development and neurosystem. The search for toxin homologs reveals possible gene function shift between toxins and nontoxins and confirms that there are no reliable toxin genes in the genome of this group. CONCLUSIONS: This study demonstrates the trade-off between different predation strategies in spiders, using either chemical or physical strategy, and provides insights into the possible mechanism underlying this trade-off. Venomless spiders need to mobilize multiple developmental and metabolic pathways related to motor function and limb mechanical strength to cover the decline in adaptability caused by the absence of venom glands.


Assuntos
Evolução Molecular , Aranhas , Animais , Aranhas/genética , Aranhas/metabolismo , Venenos de Aranha/genética , Comportamento Predatório , Filogenia , Evolução Biológica , Genoma , Seleção Genética , Adaptação Fisiológica/genética
2.
Zookeys ; 1208: 81-98, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39100128

RESUMO

Four new species of the genus Camptoscaphiella Caporiacco, 1934 are described from Xizang, China, i.e., C.metok Tong & Li, sp. nov. (♂), C.shannan Tong & Li, sp. nov. (♂♀), C.trifoliata Tong & Li, sp. nov. (♂♀) and C.zayu Tong & Li, sp. nov. (♂♀). Morphological descriptions, photographic illustrations and a distribution map of the four new species are given.

3.
Biodivers Data J ; 12: e128884, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39027382

RESUMO

Background: The genus Khorata Huber, 2005 contains 51 species. It is distributed in the Indo-Malayan Region. Nine species have been recorded from Vietnam. New information: Khorataninhbinh sp. nov. is described as a new species from Vietnam. In addition, a list of all Khorata species from Vietnam is also provided.

4.
Zookeys ; 1205: 333-348, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38984213

RESUMO

A new species of the genus Bannana Tong & Li, 2015 and a new species of the genus Trilacuna Tong & Li, 2007 are recorded from Xishuangbanna, Yunnan Province: Bannanazhengguoi Tong & Li, sp. nov. (♂♀) and Trilacunaaoxian Tong & Li, sp. nov. (♂♀). An identification key to species of the genus Bannana from Xishuangbanna is provided. Detailed diagnoses, descriptions, and photomicroscopy images of new species are provided.

5.
Adv Mater ; : e2407359, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38936413

RESUMO

Sodium-ion batteries (SIBs), recognized for balanced energy density and cost-effectiveness, are positioned as a promising complement to lithium-ion batteries (LIBs) and a substitute for lead-acid batteries, particularly in low-speed electric vehicles and large-scale energy storage. Despite their extensive potential, concerns about range anxiety due to lower energy density underscore the importance of fast-charging technologies, which drives the exploration of high-rate electrode materials. Polyanionic cathode materials are emerging as promising candidates in this regard. However, their intrinsic limitation in electronic conductivity poses challenges for synchronized electron and ion transport, hindering their suitability for fast-charging applications. This review provides a comprehensive analysis of sodium ion migration during charging/discharging, highlighting it as a critical rate-limiting step for fast charging. By delving into intrinsic dynamics, key factors that constrain fast-charging characteristics are identified and summarized. Innovative modification routes are then introduced, with a focus on shortening migration paths and increasing diffusion coefficients, providing detailed insights into feasible strategies. Moreover, the discussion extends beyond half cells to full cells, addressing challenges and opportunities in transitioning polyanionic materials from the laboratory to practical applications. This review aims to offer valuable insights into the development of high-rate polyanionic cathodes, acknowledging their pivotal role in advancing fast-charging SIBs.

6.
Biodivers Data J ; 12: e126716, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38912107

RESUMO

Background: Only two Otacilia Thorell, 1897 species with troglobitic characteristics have been recorded from Laos and no records of troglobitic Otacilia species from China. New information: A new troglobitic species is reported from Guangxi, China: Otaciliakhezu Lin & Li, sp. nov. (♂♀). Photos and morphological descriptions of the new species are presented; the type specimens of the new species are deposited in the Institute of Zoology, Chinese Academy of Sciences (IZCAS), Beijing.

7.
Zookeys ; 1202: 255-286, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38836194

RESUMO

In this study, eight new species are described from the subtropical parts of Yunnan Province in southwestern China: Belisanahonghe Zhang, Li & Yao, sp. nov. (♂♀), B.jiuxiang Zhang, Li & Yao, sp. nov. (♂♀), B.lincang Zhang, Li & Yao, sp. nov. (♂♀), B.luxi Zhang, Li & Yao, sp. nov. (♂♀), B.tengchong Zhang, Li & Yao, sp. nov. (♂♀), B.tongi Zhang, Li & Yao, sp. nov. (♂♀), B.yongsheng Zhang, Li & Yao, sp. nov. (♂), and B.yunnan Zhang, Li & Yao, sp. nov. (♂♀). They add up to a total of 31 Belisana species from Yunnan in an updated list provided in this paper.

8.
Adv Healthc Mater ; : e2400864, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771618

RESUMO

Osteosarcoma (OS) is a primary malignant bone tumor that emanates from mesenchymal cells, commonly found in the epiphyseal end of long bones. The highly recurrent and metastatic nature of OS poses significant challenges to the efficacy of treatment and negatively affects patient prognosis. Currently, available clinical treatment strategies primarily focus on maximizing tumor resection and reducing localized symptoms rather than the complete eradication of malignant tumor cells to achieve ideal outcomes. The biomaterials-boosted immunotherapy for OS is characterized by high effectiveness and a favorable safety profile. This therapeutic approach manipulates the tumor microenvironments at the cellular and molecular levels to impede tumor progression. This review delves into the mechanisms underlying the treatment of OS, emphasizing biomaterials-enhanced tumor immunity. Moreover, it summarizes the immune cell phenotype and tumor microenvironment regulation, along with the ability of immune checkpoint blockade to activate the autoimmune system. Gaining a profound comprehension of biomaterials-boosted OS immunotherapy is imperative to explore more efficacious immunotherapy protocols and treatment options in this setting.

9.
Adv Mater ; 36(28): e2402291, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38635166

RESUMO

Lithium-based batteries (LBBs) have been highly researched and recognized as a mature electrochemical energy storage (EES) system in recent years. However, their stability and effectiveness are primarily confined to room temperature conditions. At temperatures significantly below 0 °C or above 60 °C, LBBs experience substantial performance degradation. Under such challenging extreme contexts, sodium-ion batteries (SIBs) emerge as a promising complementary technology, distinguished by their fast dynamics at low-temperature regions and superior safety under elevated temperatures. Notably, developing SIBs suitable for wide-temperature usage still presents significant challenges, particularly for specific applications such as electric vehicles, renewable energy storage, and deep-space/polar explorations, which requires a thorough understanding of how SIBs perform under different temperature conditions. By reviewing the development of wide-temperature SIBs, the influence of temperature on the parameters related to battery performance, such as reaction constant, charge transfer resistance, etc., is systematically and comprehensively analyzed. The review emphasizes challenges encountered by SIBs in both low and high temperatures while exploring recent advancements in SIB materials, specifically focusing on strategies to enhance battery performance across diverse temperature ranges. Overall, insights gained from these studies will drive the development of SIBs that can handle the challenges posed by diverse and harsh climates.

10.
J Orthop Translat ; 45: 197-210, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38685969

RESUMO

Background/objective: As the pivotal cellular mediators of bone resorption and pathological bone remodeling, osteoclasts have emerged as a prominent target for anti-resorptive interventions. Pinocembrin (PIN), a predominant flavonoid found in damiana, honey, fingerroot, and propolis, has been recognized for its potential therapeutic effects in osteolysis. The purpose of our project is to investigate the potential of PIN to prevent bone resorption in ovariectomized (OVX) mice by suppressing osteoclast production through its underlying mechanisms. Methods: The study commenced by employing protein-ligand molecular docking to ascertain the specific interaction between PIN and nuclear factor-κB (NF-κB) ligand (RANKL). Subsequently, PIN was introduced to bone marrow macrophages (BMMs) under the stimulation of RANKL. The impact of PIN on osteoclastic activity was assessed through the utilization of a positive TRAcP staining kit and a hydroxyapatite resorption assay. Furthermore, the study investigated the generation of reactive oxygen species (ROS) in osteoclasts induced by RANKL using H2DCFDA. To delve deeper into the underlying mechanisms, molecular cascades triggered by RANKL, including NF-κB, ROS, calcium oscillations, and NFATc1-mediated signaling pathways, were explored using Luciferase gene report, western blot analysis, and quantitative real-time polymerase chain reaction. Moreover, an estrogen-deficient osteoporosis murine model was established to evaluate the therapeutic effects of PIN in vivo. Results: In this study, we elucidated the profound inhibitory effects of PIN on osteoclastogenesis and bone resorption, achieved through repression of NF-κB and NFATc1-mediated signaling pathways. Notably, PIN also exhibited potent anti-oxidative properties by mitigating RANKL-induced ROS generation and augmenting activities of ROS-scavenging enzymes, ultimately leading to a reduction in intracellular ROS levels. Moreover, PIN effectively abrogated the expression of osteoclast-specific marker genes (Acp5, Cathepsin K, Atp6v0d2, Nfatc1, c-fos, and Mmp9), further underscoring its inhibitory impact on osteoclast differentiation and function. Additionally, employing an in vivo mouse model, we demonstrated that PIN effectively prevented osteoclast-induced bone loss resultant from estrogen deficiency. Conclusion: Our findings highlight the potent inhibitory effects of PIN on osteoclastogenesis, bone resorption, and RANKL-induced signaling pathways, thereby establishing PIN as a promising therapeutic candidate for the prevention and management of osteolytic bone diseases. The translational potential of this article: PIN serves as a promising therapeutic agent for the prevention and management of osteolytic bone diseases and holds promise for future clinical applications in addressing conditions characterized by excessive bone resorption. PIN is a natural compound found in various sources, including damiana, honey, fingerroot, and propolis. Its widespread availability and potential for therapeutic use make it an attractive candidate for further investigation and development as a clinical intervention.

11.
J Cell Mol Med ; 28(8): e18304, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38652093

RESUMO

Liver hepatocellular carcinoma (LIHC) is a significant global health issue with limited treatment options. In this study, single-cell RNA sequencing (scRNA-seq) data were used to explore the molecular mechanisms of LIHC development and identify potential targets for therapy. The expression of peroxisome proliferator-activated receptors (PPAR)-related genes was analysed in LIHC samples, and primary cell populations, including natural killer cells, T cells, B cells, myeloid cells, endothelial cells, fibroblasts and hepatocytes, were identified. Analysis of the differentially expressed genes (DEGs) between normal and tumour tissues revealed significant changes in gene expression in various cell populations. PPAR activity was evaluated using the 'AUCell' R software, which indicated higher scores in the normal versus the malignant hepatocytes. Furthermore, the DEGs showed significant enrichment of pathways related to lipid and glucose metabolism, cell development, differentiation and inflammation. A prognostic model was then constructed using 8 PPARs-related genes, including FABP5, LPL, ACAA1, PPARD, FABP4, PLIN1, HMGCS2 and CYP7A1, identified using least absolute shrinkage and selection operator-Cox regression analysis, and validated in the TCGA-LIHC, ICGI-LIRI and GSE14520 datasets. Patients with low-risk scores had better prognosis in all cohorts. Based on the expression of the eight model genes, two clusters of patients were identified by ConsensusCluster analysis. We also predicted small-molecule drugs targeting the model genes, and identified perfluorohexanesulfonic acid, triflumizole and perfluorononanoic acid as potential candidates. Finally, wound healing assay confirmed that PPARD can promote the migration of liver cancer cells. Overall, our study offers novel perspectives on the molecular mechanisms of LIHC and potential areas for therapeutic intervention, which may facilitate the development of more effective treatment regimens.


Assuntos
Carcinoma Hepatocelular , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , Simulação de Acoplamento Molecular , Receptores Ativados por Proliferador de Peroxissomo , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Prognóstico , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/genética , Perfilação da Expressão Gênica , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo
12.
Zookeys ; 1192: 141-178, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38425441

RESUMO

Ten new species of jumping spiders are described from China, including Attulusjimanisp. nov. (♂♀) from Yunnan, Colaxescibagousp. nov. (♂♀), Epeuspengisp. nov. (♂♀), Evarchazayusp. nov. (♂♀), Iciuszangsp. nov. (♂♀), Pancoriusnyingchisp. nov. (♂♀), Stertiniusliqingaesp. nov. (♂♀), and Synagelidesmedogsp. nov. (♀) from Xizang, S.tianquansp. nov. (♂♀), and Yaginumaellaerlangsp. nov. (♂♀) from Sichuan. The hitherto unknown female of Phintellalongapophysis Lei & Peng, 2013 is described for the first time. Diagnostic photos and the distributional maps for all species are provided. Four new combinations are proposed: Epeusdilucidus (Próchniewicz, 1990), comb. nov., and E.guangxi (Peng & Li, 2002), comb. nov. transferred from Plexippoides Prószynski, 1984, Phintellasufflava (Jastrzebski, 2009), comb. nov. transferred from Carrhotus Thorell, 1891, and Yaginumaellaarmata (Jastrzebski, 2011), comb. nov. transferred from Pancorius Simon, 1902.

13.
J Inherit Metab Dis ; 47(4): 757-765, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38499449

RESUMO

T cells have been shown to maintain a lower percentage (heteroplasmy) of the pathogenic m.3243A>G variant (MT-TL1, associated with maternally inherited diabetes and deafness [MIDD] and mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes [MELAS]). The mechanism(s) underlying this purifying selection, however, remain unknown. Here we report that purified patient memory CD4+ T cells have lower bulk m.3243A>G heteroplasmy compared to naïve CD4+ T cells. In vitro activation of naïve CD4+ m.3243A>G patient T cells results in lower bulk m.3243A>G heteroplasmy after proliferation. Finally, m.3243A>G patient T cell receptor repertoire sequencing reveals relative oligoclonality compared to controls. These data support a role for T cell activation in peripheral, purifying selection against high m.3243A>G heteroplasmy T cells at the level of the cell, in a likely cell-autonomous fashion.


Assuntos
Ativação Linfocitária , Síndrome MELAS , Humanos , Síndrome MELAS/genética , Linfócitos T CD4-Positivos/imunologia , Heteroplasmia/genética , RNA de Transferência de Leucina/genética , Masculino , Feminino , DNA Mitocondrial/genética , Adulto
14.
Front Med (Lausanne) ; 11: 1290729, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38348336

RESUMO

Background: Pneumoconiosis is the most important occupational disease all over the world, with high prevalence and mortality. At present, the monitoring of workers exposed to dust and the diagnosis of pneumoconiosis rely on manual interpretation of chest radiographs, which is subjective and low efficiency. With the development of artificial intelligence technology, a more objective and efficient computer aided system for pneumoconiosis diagnosis can be realized. Therefore, the present study reported a novel deep learning (DL) artificial intelligence (AI) system for detecting pneumoconiosis in digital frontal chest radiographs, based on which we aimed to provide references for radiologists. Methods: We annotated 49,872 chest radiographs from patients with pneumoconiosis and workers exposed to dust using a self-developed tool. Next, we used the labeled images to train a convolutional neural network (CNN) algorithm developed for pneumoconiosis screening. Finally, the performance of the trained pneumoconiosis screening model was validated using a validation set containing 495 chest radiographs. Results: Approximately, 51% (25,435/49,872) of the chest radiographs were labeled as normal. Pneumoconiosis was detected in 49% (24,437/49,872) of the labeled radiographs, among which category-1, category-2, and category-3 pneumoconiosis accounted for 53.1% (12,967/24,437), 20.4% (4,987/24,437), and 26.5% (6,483/24,437) of the patients, respectively. The CNN DL algorithm was trained using these data. The validation set of 495 digital radiography chest radiographs included 261 cases of pneumoconiosis and 234 cases of non-pneumoconiosis. As a result, the accuracy of the AI system for pneumoconiosis identification was 95%, the area under the curve was 94.7%, and the sensitivity was 100%. Conclusion: DL algorithm based on CNN helped screen pneumoconiosis in the chest radiographs with high performance; thus, it could be suitable for diagnosing pneumoconiosis automatically and improve the efficiency of radiologists.

15.
bioRxiv ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38405900

RESUMO

Understanding how intra-tumoral immune populations coordinate to generate anti-tumor responses following therapy can guide precise treatment prioritization. We performed systematic dissection of an established adoptive cellular therapy, donor lymphocyte infusion (DLI), by analyzing 348,905 single-cell transcriptomes from 74 longitudinal bone-marrow samples of 25 patients with relapsed myeloid leukemia; a subset was evaluated by protein-based spatial analysis. In acute myelogenous leukemia (AML) responders, diverse immune cell types within the bone-marrow microenvironment (BME) were predicted to interact with a clonally expanded population of ZNF683 + GZMB + CD8+ cytotoxic T lymphocytes (CTLs) which demonstrated in vitro specificity for autologous leukemia. This population, originating predominantly from the DLI product, expanded concurrently with NK and B cells. AML nonresponder BME revealed a paucity of crosstalk and elevated TIGIT expression in CD8+ CTLs. Our study highlights recipient BME differences as a key determinant of effective anti-leukemia response and opens new opportunities to modulate cell-based leukemia-directed therapy.

16.
Zootaxa ; 5397(1): 116-126, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38221216

RESUMO

In this paper, two new species of the genus Amaurobius C. L. Koch, 1837 of the family Amaurobiidae Thorell, 1869 are reported from Sichuan Province, China: A. danba Lin & Li, sp. nov. () and A. yaan Lin & Li, sp. nov. (). Photos and morphological descriptions of the new species are presented; the type specimens of the new species are deposited in the Institute of Zoology, Chinese Academy of Sciences (IZCAS), Beijing.


Assuntos
Aranhas , Animais , China
17.
Zool Res ; 45(1): 152-159, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38247177

RESUMO

We examined the global biogeography of the Scytodes thoracica group of spitting spiders based on 23 years of sampling at the species level (61 species in the thoracica group and 84 species of Scytodes) using DNA data from six loci. Our results indicated that the thoracica group initially dispersed from Southeast Asia to East Africa between 46.5 and 33.0 million years ago, and dispersal events intensified between Southeast/South Asia and East/South Africa from the early to late Miocene. The timing of these events indicates that Asian-African faunal exchange of the thoracica group was driven by the Indian monsoon, and the pattern of dispersal suggests that colonialization took root when the Indian monsoon shifted from a North-South direction to an East-West direction from the middle Eocene.


Assuntos
Aranhas , Animais , Aranhas/genética
18.
Nat Commun ; 15(1): 32, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167262

RESUMO

Single-cell transcriptomics has become the definitive method for classifying cell types and states, and can be augmented with genotype information to improve cell lineage identification. Due to constraints of short-read sequencing, current methods to detect natural genetic barcodes often require cumbersome primer panels and early commitment to targets. Here we devise a flexible long-read sequencing workflow and analysis pipeline, termed nanoranger, that starts from intermediate single-cell cDNA libraries to detect cell lineage-defining features, including single-nucleotide variants, fusion genes, isoforms, sequences of chimeric antigen and TCRs. Through systematic analysis of these classes of natural 'barcodes', we define the optimal targets for nanoranger, namely those loci close to the 5' end of highly expressed genes with transcript lengths shorter than 4 kB. As proof-of-concept, we apply nanoranger to longitudinal tracking of subclones of acute myeloid leukemia (AML) and describe the heterogeneous isoform landscape of thousands of marrow-infiltrating immune cells. We propose that enhanced cellular genotyping using nanoranger can improve the tracking of single-cell tumor and immune cell co-evolution.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Leucemia Mieloide Aguda , Humanos , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Fenótipo , Perfilação da Expressão Gênica/métodos
19.
Adv Mater ; 36(2): e2304040, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37461204

RESUMO

As alternatives to batteries with organic electrolytes, aqueous zinc-based batteries (AZBs) have been intensively studied. However, the sluggish kinetics, side reactions, structural collapse, and dissolution of the cathode severely compromise the commercialization of AZBs. Among various strategies to accelerate their practical applications, multi-ion engineering shows great feasibility to maintain the original structure of the cathode and provide sufficient energy density for high-performance AZBs. Though multi-ion engineering strategies could solve most of the problems encountered by AZBs and show great potential in achieving practical AZBs, the comprehensive summaries of the batteries undergo electrochemical reactions involving more than one charge carrier is still in deficiency. The ambiguous nomenclature and classification are becoming the fountainhead of confusion and chaos. In this circumstance, this review overviews all the battery configurations and the corresponding reaction mechanisms are investigated in the multi-ion engineering of aqueous zinc-based batteries. By combing through all the reported works, this is the first to nomenclate the different configurations according to the reaction mechanisms of the additional ions, laying the foundation for future unified discussions. The performance enhancement, fundamental challenges, and future developing direction of multi-ion strategies are accordingly proposed, aiming to further accelerate the pace to achieve the commercialization of AZBs with high performance.

20.
Blood ; 143(10): 895-911, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-37890146

RESUMO

ABSTRACT: A major hurdle in adoptive T-cell therapy is cell exhaustion and failure to maintain antitumor responses. Here, we introduce an induced pluripotent stem cell (iPSC) strategy for reprogramming and revitalizing precursor exhausted B-cell maturation antigen (BCMA)-specific T cells to effectively target multiple myeloma (MM). Heteroclitic BCMA72-80 (YLMFLLRKI)-specific CD8+ memory cytotoxic T lymphocytes (CTL) were epigenetically reprogrammed to a pluripotent state, developed into hematopoietic progenitor cells (CD34+ CD43+/CD14- CD235a-), differentiated into the T-cell lineage and evaluated for their polyfunctional activities against MM. The final T-cell products demonstrated (1) mature CD8αß+ memory phenotype, (2) high expression of activation or costimulatory molecules (CD38, CD28, and 41BB), (3) no expression of immune checkpoint and senescence markers (CTLA4, PD1, LAG3, and TIM3; CD57), and (4) robust proliferation and polyfunctional immune responses to MM. The BCMA-specific iPSC-T cells possessed a single T-cell receptor clonotype with cognate BCMA peptide recognition and specificity for targeting MM. RNA sequencing analyses revealed distinct genome-wide shifts and a distinctive transcriptional profile in selected iPSC clones, which can develop CD8αß+ memory T cells. This includes a repertoire of gene regulators promoting T-cell lineage development, memory CTL activation, and immune response regulation (LCK, IL7R, 4-1BB, TRAIL, GZMB, FOXF1, and ITGA1). This study highlights the potential application of iPSC technology to an adaptive T-cell therapy protocol and identifies specific transcriptional patterns that could serve as a biomarker for selection of suitable iPSC clones for the successful development of antigen-specific CD8αß+ memory T cells to improve the outcome in patients with MM.


Assuntos
Antineoplásicos , Antígenos CD8 , Células-Tronco Pluripotentes Induzidas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Células-Tronco Pluripotentes Induzidas/metabolismo , Antígeno de Maturação de Linfócitos B/metabolismo , Linfócitos T Citotóxicos , Antineoplásicos/metabolismo
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