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BACKGROUND: Pulmonary fibrosis (PF) is a common interstitial pneumonia disease, also occurred in post-COVID-19 survivors. The mechanism underlying the anti-PF effect of Qing Fei Hua Xian Decotion (QFHXD), a traditional Chinese medicine formula applied for treating PF in COVID-19 survivors, is unclear. This study aimed to uncover the mechanisms related to the anti-PF effect of QFHXD through analysis of network pharmacology and experimental verification. METHODS: The candidate chemical compounds of QFHXD and its putative targets for treating PF were achieved from public databases, thereby we established the corresponding "herb-compound-target" network of QFHXD. The protein-protein interaction network of potential targets was also constructed to screen the core targets. Furthermore, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to predict targets, and pathways, then validated by in vivo experiments. RESULTS: A total of 188 active compounds in QFHXD and 50 target genes were identified from databases. The key therapeutic targets of QFHXD, such as PI3K/Akt, IL-6, TNF, IL-1ß, STAT3, MMP-9, and TGF-ß1 were identified by KEGG and GO analysis. Anti-PF effects of QFHXD (in a dose-dependent manner) and prednisone were confirmed by HE, Masson staining, and Sirius red staining as well as in vivo Micro-CT and immunohistochemical analysis in a rat model of bleomycin-induced PF. Besides, QFXHD remarkably inhibits the activity of PI3K/Akt/NF-κB and TGF-ß1/Smad2/3. CONCLUSIONS: QFXHD significantly attenuated bleomycin-induced PF via inhibiting inflammation and epithelial-mesenchymal transition. PI3K/Akt/NF-κB and TGF-ß1/Smad2/3 pathways might be the potential therapeutic effects of QFHXD for treating PF.
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Medicamentos Herbarios Chinos , Farmacología en Red , Mapas de Interacción de Proteínas , Fibrosis Pulmonar , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Animales , Ratas , Masculino , Mapas de Interacción de Proteínas/efectos de los fármacos , Bleomicina , Factor de Crecimiento Transformador beta1/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Humanos , COVID-19/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Medicina Tradicional China/métodos , Tratamiento Farmacológico de COVID-19RESUMEN
The ectoparasitoid Habrobracon hebetor (Hymenoptera: Braconidae) exhibits a broad parasitic capability towards various lepidopteran pests, with venom serving as a crucial virulent factor ensuring successful parasitization and subsequent host mortality. Analyzing the constituents of its venom is essential for elucidating the mechanisms underlying efficient host killing by this parasitoid and for exploring potentially functional venom proteins. Through a transcriptomic analysis, a total of 34 venom proteins were identified within the venom of H. hebetor, encompassing known components such as serine protease, metalloproteinase, esterase, and serine protease inhibitors commonly present in parasitoid venoms. Unique components like paralytic protein and ion transport peptide-like were identified, possibly specific to certain parasitoids, along with novel proteins with uncharacterized functions. Spatial gene expression profiling of the identified venom proteins using transcriptomic data, corroborated by quantitative PCR validation for 13 randomly selected proteins, revealed abundant expression levels in the venom apparatus, affirming them as genuine venom components. Notably, the paralytic protein exhibited prominent expression, with the highest FPKM (fragments per kilobase of transcript per million fragments mapped) value of 24,704.87 in the venom apparatus, indicative of its significant role in successful parasitism by H. hebetor. The identification of these venom proteins establishes a foundation for the further exploration of bioactive agents for pest management strategies.
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The stink bug Arma custos (Hemiptera: Pentatomidae) is a predatory enemy successfully used for biocontrol of lepidopteran and coleopteran pests in notorious invasive species. In this study, a high-quality chromosome-scale genome assembly of A. custos was achieved through a combination of Illumina sequencing, PacBio HiFi sequencing, and Hi-C scaffolding techniques. The final assembled genome was 969.02 Mb in size, with 935.94 Mb anchored to seven chromosomes, and a scaffold N50 length of 135.75 Mb. This genome comprised 52.78% repetitive elements. The detected complete BUSCO score was 99.34%, indicating its completeness. A total of 13,708 protein-coding genes were predicted in the genome, and 13219 of them were annotated. This genome provides an invaluable resource for further research on various aspects of predatory bugs, such as biology, genetics, and functional genomics.
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Genoma de los Insectos , Heterópteros , Animales , Heterópteros/genética , Cromosomas de InsectosRESUMEN
Glycosylation plays a very important role in plant secondary metabolic modifications. Neodiosmin, identified as diosmetin-7-O-neohesperidoside, not only acts to mitigate bitterness and enhance the flavor of food but also serves as a pivotal metabolite that reinforces plant immunity. Investigating its biosynthetic pathway in plants is crucial for optimizing fruit quality and fortifying plant immune responses. In this study, through analysis of transcriptomic data from Astilbe chinensis, we identified two novel uridine diphosphate (UDP)-glycosyltransferases (UGTs): Ach14791 (AcUGT73C18), responsible for flavonoid 7-O-glycosylation and Ach15849 (AcUGT79B37), involved in flavonoid-7-O-glucoside-2â³-O-rhamnosylation. By delving into enzymatic properties and catalytic promiscuity, we developed a biosynthesis route of neodiosmin by establishing a one-pot enzyme-catalyzed cascade reaction. Simultaneously, lonicerin and rhoifolin were also successfully synthesized using the same one-pot dual-enzyme catalytic reaction. Taken together, our findings not only identified two novel UGTs involved in neodiosmin biosynthesis but also provided important biocatalytic components for the microorganism-based biosynthesis of flavonoid-7-O-disaccharide compounds.
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Flavonoides , Glicosiltransferasas , Glicosiltransferasas/genética , Glicosiltransferasas/metabolismo , Glicosilación , Flavonoides/metabolismo , Uridina Difosfato/metabolismo , Glicósidos , FilogeniaRESUMEN
Background: Radiotherapy is an indispensable part of the multidisciplinary treatment of breast cancer (BC). Due to the potential for serious side effects from ionizing radiation in the treatment of breast cancer, which can adversely affect the patient's quality of life, the radiation dose is often limited. This limitation can result in an incomplete eradication of tumors. Methods: In this study, biomimetic copper single-atom catalysts (platelet cell membrane camouflaging, PC) were synthesized with the aim of improving the therapeutic outcomes of radiotherapy for BC. Following guidance to the tumor site facilitated by the platelet cell membrane coating, PC releases a copper single-atom nanozyme (SAzyme). This SAzyme enhances therapeutic effects by generating reactive oxygen species from H2O2 and concurrently inhibiting the self-repair mechanisms of cancer cells through the consumption of intracellular glutathione (GSH) within the tumor microenvironment. PC-augmented radiotherapy induces immunogenic cell death, which triggers an immune response to eradicate tumors. Results: With the excellent biocompatibility, PC exhibited precise tumor-targeting capabilities. Furthermore, when employed in conjunction with radiotherapy, PC showed impressive tumor elimination results through immunological activation. Remarkably, the tumor suppression rate achieved with PC-enhanced radiotherapy reached an impressive 93.6%. Conclusion: Therefore, PC presents an innovative approach for designing radiosensitizers with tumor-specific targeting capabilities, aiming to enhance the therapeutic impact of radiotherapy on BC.
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Neoplasias de la Mama , Radioinmunoterapia , Humanos , Femenino , Cobre/farmacología , Peróxido de Hidrógeno , Calidad de Vida , Neoplasias de la Mama/radioterapia , Glutatión , Microambiente TumoralRESUMEN
Predatory bugs employ a salivary venom apparatus to generate complex venoms for capturing and digesting prey. The venom apparatus consists of different glands for the production of distinct venom sets, but the underlying mechanisms behind this process remain poorly understood. Here we present a comprehensive analysis of the morphological, functional, compositional and transcriptional characteristics of venoms derived from posterior main gland (PMG), anterior main gland (AMG), and accessory gland (AG) of the assassin bug Sycanus croceovittatus. Structural observations revealed the intricate constructions of the venom apparatus, enabling the production and storage of three distinct venom sets in anatomically varied glands and allowing them to be modulated in a context-dependent manner upon utilization. There were remarkable differences in the biological activities exhibited by PMG, AMG, and AG venoms. Proteotranscriptomic analysis demonstrated that these venoms displayed compositional heterogeneity at both the quantity and variety levels of proteins. Transcriptional profiles of the identified venom proteins revealed gland-specific or biased expression patterns. These findings indicate that the divergence in venom profiles among different glands arises from morphological, functional, compositional and transcriptional constraints on the venom apparatus, reflecting remarkable morphogenesis and regulatory gene networks responsible for the compartmentalized production of venom proteins in different glands.
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Dipeptidyl peptidase IV (DPPIV) is a proline-specific serine peptidase that remains poorly investigated in terms of venom composition. Here, we describe the molecular characteristics and possible functions of DPPIV as a major venom component of the ant-like bethylid ectoparasitoid, Scleroderma guani, named SgVnDPPIV. The SgVnDPPIV gene was cloned, which encodes a protein with the conserved catalytic triads and substrate binding sites of mammalian DPPIV. This venom gene is highly expressed in the venom apparatus. Recombinant SgVnDPPIV, produced in Sf9 cells using the baculovirus expression system, has high enzymatic activity, which can be efficiently inhibited by vildagliptin and sitagliptin. Functional analysis revealed that SgVnDPPIV affects genes related to detoxification, lipid synthesis and metabolism, response to stimuli, and ion exchange in pupae of Tenebrio molitor, an envenomated host of S. guani. The present work contributes towards understanding the role of venom DPPIV involved in the interaction between parasitoid wasp and its host.
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Tenebrio , Avispas , Animales , Dipeptidil Peptidasa 4/genética , Avispas/genética , Serina Proteasas/metabolismo , Venenos de Avispas/química , Tenebrio/metabolismo , Mamíferos/metabolismoRESUMEN
PURPOSE: To explore the optimal treatment strategy and relevant prognostic analysis for hypopharyngeal squamous-cell carcinoma patients (HSCC) with T3-T4 or node-positive. METHODS AND MATERIALS: From 2004 to 2018, data for 2574 patients from the Surveillance, Epidemiology, and End Results database (SEER) and 66 patients treated at our center from 2013 to 2022 with T3-T4 or N + HSCC were collected. Patients in the SEER cohort were randomly assigned to the training set or validation set at a 7:3 ratio. Variables with statistically significant (P < 0.05) in univariate COX regression analysis or clinical significance were included in the multivariate COX regression model and subsequently used to construct the nomogram. RESULTS: The 3-year OS (52.9%vs44.4%, P < 0.01) and 3-year CSS rate (58.7%vs51.5%, P < 0.01) rates in the surgery combined with postoperative adjuvant therapy (S + ADT) group were superior to the radiotherapy combined with chemotherapy (CRT) group. The multivariate Cox regression analysis of the training group showed that age, race, marital status, primary site, T stage, N stage, and treatment modalities were correlated with OS and CSS. Based on those variables, we constructed nomograms for OS and CSS. Both the internal and external validation showed high prediction accuracy of the nomogram. CONCLUSION: Among patients with T3-T4 or node-positive, S + ADT was associated with superior OS and CSS compared to those treated with primary CRT, while the survival rate in the CRT group was comparable to S + ADT group in T2-T3 disease. The internal and external verification shows that the prognostic model has good discrimination ability and accuracy.
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Neoplasias de Cabeza y Cuello , Nomogramas , Humanos , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello , Modelos de Riesgos Proporcionales , Programa de VERFRESUMEN
Objectives: We aimed to investigate the preventative effect of Qing Fei Hua Xian Decoction (QFHXD) against pulmonary fibrosis (PF) and its potential mechanisms. Materials and Methods: Bleomycin (BLM)-induced rats were respectively treated with 413.3, 826.6, and 1239.9 mg/kg of QFHXD and prednisone for 28 days. The lung tissues of rats were collected on day 28 for histological and western blotting analysis. Results: QFHXD significantly reduced alveolus inflammation, collagen accumulation, and fibrosis deposition in BLM-induced PF rats (P<0.05). Collagen I and III, vimentin, and α-smooth muscle actin(α-SMA) expression levels were likewise decreased in PF rats treated with QFHXD (P<0.05). Additionally, QFHXD increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) while decreasing NADPH oxidase 4 (NOX4) expression (P<0.05). Furthermore, QFHXD suppressed the PF progression by down-regulating Angiotensin-Converting Enzyme (ACE) -Angiotensin II (AngII) -Angiotensin II Type 1 Receptor (AT1R) axis (P<0.01) and up-regulating Angiotensin-Converting Enzyme 2 (ACE2) -Angiotensin-(1-7) (Ang-(1-7)) -Mas axis (P<0.05). Conclusion: QFHXD suppressed inflammatory infiltration and PF brought on by BLM in lung tissues through reducing oxidative stress by maintaining the equilibrium of ACE-AngII-AT1R and ACE2-Ang-(1-7) -Mas axes. This study may provide a novel clinical therapy option for PF.
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The metallothionein 1 (MT1) family was previously shown to be involved in metal ion homeostasis, DNA damage, oxidative stress, and carcinogenesis. Our team's previous study showed that MT1X is most closely associated with ccRCC. However, its role in clear cell RCC (ccRCC) remains unclear. The present study aimed to demonstrate MT1X's prognostic value, potential biologic function, impact on the immune system, and influence on cell growth, the cell cycle, apoptosis, and migration in the setting of ccRCC. The relationship between clinical pathologic features and MT1X was analyzed using bioinformatics. We knocked down MT1X in the ccRCC cell line 786O with si-MT1X to verify the results of the bioinformatic analysis at the cytological level. Apoptosis assay, cell cycle assay, wound-healing assay, colony formation assay, and RT-qPCR were performed. MT1X is correlated with the stage (T and M) and grade and is able to be an independent prognostic factor for ccRCC. The TISIDB database analysis showed a significant correlation between MT1X and tumor-infiltrating lymphocytes such as central memory CD8+ T cells and γΔT cells. MT1X was also positively related to immunomodulators such as TGFB1 and CXCR4. We also found that MT1X knockdown inhibits cell growth, induces apoptosis, arrests cells in the S cell cycle, and inhibits the wound healing proportion in ccRCC. Gene set enrichment analysis and quantitative PCR (q-PCR) analysis found that down-regulation of MT1X reduced the accumulation of hypoxia-associated factors. Bioinformatic analysis associated increased MT1X expression with a worse prognosis. Laboratory experiments confirmed bioinformatic findings. MT1X was also found to be an independent prognostic biomarker for ccRCC and is involved in immune system regulation.
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Productos Biológicos , Carcinoma de Células Renales , Neoplasias Renales , Humanos , Biomarcadores , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/genética , Metalotioneína , OncogenesRESUMEN
Background: This study aims to evaluate the overall and breast cancer-specific survival (BCSS) after breast-conserving surgery (BCS) plus radiotherapy (RT) compared with mastectomy plus RT in resectable breast cancer. Moreover, the aim is to also identify the subgroups who benefit from BCS plus RT and establish a predictive nomogram for stage II patients. Methods: Stage I−III breast cancer patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 1990 and 2016. Patients with available clinical information were split into two groups: BCS plus RT and mastectomy plus RT. Kaplan−Meier survival analysis, univariate and multivariate regression analysis, and propensity score matching were used in the study. Hazard ratio (HR) was calculated based on stratified Cox univariate regression analyses. A prognostic nomogram by multivariable Cox regression model was developed for stage II patients, and consistency index (C-index) and calibration curve were used to evaluate the accuracy of the nomogram in the training and validation set. Results: A total of 24,590 eligible patients were enrolled. The difference in overall survival (OS) and BCSS remained significant in stage II patients both before and after PSM (after PSM: OS: HR = 0.8536, p = 0.0115; BCSS: HR = 0.7803, p = 0.0013). In stage II patients, the survival advantage effect of BCS plus RT on OS and BCSS was observed in the following subgroups: any age, smaller tumor size (<1 cm), stage IIA (T2N0, T0−1N1), ER (+), and any PR status. Secondly, the C-indexes for BCSS prediction was 0.714 (95% CI 0.694−0.734). The calibration curves showed perfect agreement in both the training and validation sets. Conclusions: BCS plus RT significantly improved the survival rates for patients of stage IIA (T2N0, T0−1N1), ER (+). For stage II patients, the nomogram was a good predictor of 5-, 10-, and 15-year BCSS. Our study may help guide treatment decisions and prolong the survival of stage II breast cancer patients.
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Neoplasias de la Mama , Mastectomía Segmentaria , Mastectomía , Radioterapia Adyuvante , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mastectomía/mortalidad , Mastectomía Segmentaria/métodos , Mastectomía Segmentaria/mortalidad , Estadificación de Neoplasias , Radioterapia Adyuvante/mortalidad , Programa de VERF , SobrevidaRESUMEN
In insects, serine proteases and serine protease homologs (SPs/SPHs) are involved in a variety of physiological processes including digestion, development, and immunity. Here, we identified 112 SP and 88 SPH genes in the genome of the yellow mealworm, Tenebrio molitor. Based on the features of domain structure, they were divided into "S" group containing single Tryp-SPc or Tryp-SPHc domain, "C" group containing 1-4 CLIP domain (CLIPA-D) and "M" group containing the CBD, CUB, EGF, Fz, Gd, LDLa, PAN, SEA, SR, Sushi, and TSP domains, and have 115, 48, and 37 gene members, respectively. According to the active sites in the catalytic triad, the putative trypsin, chymotrypsin, or elastase-like enzyme specificity of the identified SPs/SPHs were predicted. Phylogenetic and genomic location analyses revealed that gene duplication exists in the large amount of SPs/SPHs. Gene expression profiling using RNA-seq data along with real time reverse transcription-polymerase chain reaction analysis showed that most SP/SPH genes display life stage specific expression patterns, indicating their important roles in development. Many SP/SPH genes are specifically or highly expressed in the gut, salivary gland, fat body, hemocyte, ovary, and testis, suggesting that they participate in digestion, immunity, and reproduction. The findings lay the foundation for further functional characterization of SPs/SPHs in T. molitor.
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Serina Proteasas , Tenebrio , Animales , Quimotripsina/genética , Factor de Crecimiento Epidérmico/genética , Femenino , Masculino , Elastasa Pancreática/genética , Filogenia , Serina Proteasas/química , Tenebrio/genética , Tenebrio/metabolismo , Tripsina/genéticaRESUMEN
The Solitary Fibrous Tumor (SFT) is a rare mesenchymal neoplasm that arises mainly from the pleura. The sinonasal tract is generally not affected by SFT, and less than 100 cases have been reported in the English literature to date. We report an extremely rare SFT of the nasal cavity and paranasal sinuses extending into the anterior frontal fossa through the floor of the anterior skull base. To our knowledge, this case is the fourth SFT of the sinonasal tract involving the anterior frontal fossa in the world. Meanwhile, the tumor, measuring 13 × 6 cm in images, is the largest SFT of the sinonasal tract compared to previously reported cases. Three surgical procedures, including a transcranial one, were performed for the patient to achieve complete removal of the tumor. The diagnosis of SFT was established primarily by immunohistochemical positivity for CD34, STAT6, and negativity for S-100 protein. We emphasize the possibility of recurrence in SFT, and close follow-up is necessary with the help of nasal endoscopy and imaging approaches.
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Breast cancer is globally the most common invasive cancer in women and remains one of the leading causes of cancer-related deaths. Surgery, radiotherapy, chemotherapy, immunotherapy, and endocrine therapy are currently the main treatments for this cancer type. However, some breast cancer patients are prone to drug resistance related to chemotherapy or immunotherapy, resulting in limited treatment efficacy. Consequently, traditional Chinese medicinal materials (TCMMs) as natural products have become an attractive source of novel drugs. In this review, we summarized the current knowledge on the active components of animal-derived TCMMs, including Ophiocordycepssinensis-derived cordycepin, the aqueous and ethanolic extracts of O.sinensis, norcantharidin (NCTD), Chansu, bee venom, deer antlers, Ostreagigas, and scorpion venom, with reference to marked anti-breast cancer effects due to regulating cell cycle arrest, proliferation, apoptosis, metastasis, and drug resistance. In future studies, the underlying mechanisms for the antitumor effects of these components need to be further investigated by utilizing multi-omics technologies. Furthermore, large-scale clinical trials are necessary to validate the efficacy of bioactive constituents alone or in combination with chemotherapeutic drugs for breast cancer treatment.
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Neoplasias de la Mama , Ciervos , Animales , Neoplasias de la Mama/tratamiento farmacológico , Puntos de Control del Ciclo Celular , China , Femenino , Humanos , InmunoterapiaRESUMEN
ATP-binding cassette (ABC) transporters, one of the largest transmembrane protein families, transport a diverse number of substate across membranes. Details of their diverse physiological functions have not been established. Here, we identified 87 ABC transporter genes in the genomes of Tenebrio molitor along with those from Asbolus verrucosus (104), Hycleus cichorii (65), and Hycleus phaleratus (80). Combining these genes (336 in total) with genes reported in Tribolium castaneum (73), we analyzed the phylogeny of ABC transporter genes in all five Tenebrionids. They are assigned into eight subfamilies (ABCA-H). In comparison to other species, the ABCC subfamily in this group of beetles appears expanded. The expression profiles of the T. molitor genes at different life stages and in various tissues were also investigated using transcriptomic analysis. Most of them display developmental specific expression patterns, suggesting to us their possible roles in development. Most of them are highly expressed in detoxification-related tissues including gut and Malpighian tubule, from which we infer their roles in insecticide resistance. We detected specific or abundant expressions of many ABC transporter genes in various tissues such as salivary gland, ovary, testis, and antenna. This new information helps generate new hypotheses on their biological significance within tissues.
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Escarabajos , Tenebrio , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Adenosina Trifosfato , Animales , Escarabajos/metabolismo , Femenino , Genómica , Masculino , Filogenia , Tenebrio/genética , Tenebrio/metabolismoRESUMEN
The Wnt gene family is involved in a wide range of developmental processes. Despite its significance, the evolution and function of Wnt genes remain largely unclear. Here, an exhaustive survey of Wnt genes was conducted in Tenebrio molitor and 17 other beetle genomes. A total of 146 Wnt genes were identified, creating a comprehensive coleopteran Wnt gene catalog. Comparative genomics indicates that dynamic evolutionary patterns of Wnt gene loss and duplication occurred in Coleoptera, leading to the diverse Wnt gene repertoire in various beetles. A striking loss of particular Wnt gene subfamilies occurs in Coleoptera. Remarkably, Wnt gene duplication was discovered for the first time in insects. Further analysis of Wnt gene expression in T. molitor indicates that each Wnt gene, including the duplicated ones, has a unique spatial or temporal expression pattern. The current study provides valuable insight into the evolution and functional validation of Wnt genes in Coleoptera.
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Escarabajos , Tenebrio , Animales , Escarabajos/genética , Genoma , Tenebrio/genética , Tenebrio/metabolismoRESUMEN
Regulatory T cells (Tregs) play an important role in maintaining immune homeostasis and, within tumors, their upregulation is common and promotes an immunosuppressive microenvironment. Therapeutic strategies that can eliminate Tregs in the tumor (i.e., therapies that do not run the risk of affecting normal tissues), are urgently needed for the development of cancer immunotherapies. Here we report our discovery of B-cell lymphoma extra-large (BCL-XL) as a potential molecular target of tumor-infiltrating (TI) Tregs. We show that pharmacological degradation of BCL-XL using a newly developed platelet-sparing BCL-XL Proteolysis-targeting chimera (PROTAC) induces the apoptosis of TI-Tregs and the activation of TI-CD8+ T cells. Moreover, these activities result in an effective suppression of syngeneic tumor growth in immunocompetent, but not in immunodeficient or CD8+ T cell-depleted mice. Notably, treatment with BCL-XL PROTAC does not cause detectable damage within several normal tissues or thrombocytopenia. These findings identify BCL-XL as a target in the elimination of TI-Tregs as a component of cancer immunotherapies, and that the BCL-XL-specific PROTAC has the potential to be developed as a therapeutic for cancer immunotherapy.
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Linfocitos Infiltrantes de Tumor/metabolismo , Linfocitos T Reguladores/metabolismo , Animales , Sistemas CRISPR-Cas/genética , Sistemas CRISPR-Cas/fisiología , Supervivencia Celular/genética , Supervivencia Celular/fisiología , Células Cultivadas , Femenino , Citometría de Flujo , Immunoblotting , Ratones , Ratones Endogámicos C57BL , Proteolisis , Proteína bcl-X/genética , Proteína bcl-X/metabolismoRESUMEN
Here, we report a novel RNA virus from an encyrtid endoparasitoid wasp (Diversinervus elegans). This virus has a genome of 8845 nucleotides in length with a poly(A) tail. It contains one open reading frame (ORF) encoding a single polyprotein that shares the most significant similarity to the polyproteins of dicistroviruses. Phylogenetic analysis suggested that this virus belongs to the family Dicistroviridae from the order Picornavirales, but its genomic organization is distinct from that of the other known dicistroviruses, which have two ORFs. Consequently, we propose that this virus is a member of a new species in the order Picornavirales, and have named it "Diversinervus elegans virus" (DEV).
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Dicistroviridae/genética , Genoma Viral/genética , Virus ARN/genética , Avispas/virología , Animales , Sistemas de Lectura Abierta/genética , Filogenia , Poliproteínas/genética , ARN Viral/genética , Alineación de Secuencia , Análisis de Secuencia de ADN/métodos , Proteínas Virales/genéticaRESUMEN
The precision and efficiency of the registration of megavolt-level electronic portal imaging devices (EPID) images with the naked eye in the orthogonal window are reduced. This study aims to develop a new registration algorithm with enhanced accuracy and efficiency. Ten setup errors with different translation and rotation were simulated with the phantom. For each error, one set of simulated computer tomography images and EPID images were acquired and registered with the traditional and the new method. The traditional method was performed by two senior physicists with the Varian Offline Review software. The new method is basing on the comparison of the precise contours of the same bone structure in the digital reconstruction radiography images and the EPID images, and the contours were fitted with an automatic edge detection algorithm based on gradient images. The average error of the new method was decreased by 44.44%, 28.33%, 49.09% in the translation of X, Y, and Z axes (The traditional vs. the new: X axes, 0.45 mm vs. 0.25 mm; Y axes, 0.75 mm vs. 0.35 mm; Z axes, 0.55 mm vs. 0.28 mm), 42.86% and 40.48% in the rotation of X and Z axes (The traditional vs. the new: X axes, 0.49° vs. 0.28°; Z axes, 0.42° vs. 0.25°), respectively. The average elapsed time in the new method was reduced by 11.14% (The traditional vs. the new: 44 s vs. 39.1 s). The new registration method has significant advantages of accuracy and efficiency compared with the traditional method.