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1.
Sci Rep ; 14(1): 25133, 2024 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-39448633

RESUMEN

At present, the speed of the reel of soybean combine harvester is mainly adjusted manually, and basically does not have the ability to automatically adjust the speed of the reel according to changes in crops or working speed. In the maize-soybean strip intercropping mode, soybean plants are densely planted. During harvesting, the feeding rate increases, making it even more necessary to adjust the reel speed according to the growth status of the crops. This article uses PLC as the main control platform to design a reel speed control system for the existing combine harvester. Tests have shown that the control system can meet the requirements for reel speed control. The relative error of the reel control system's speed test is 2.6%, the relative error of the operating speed is 6.77%, and the maximum relative error of the automatic control of the reel speed is 5.38%. Compared with traditional reel, it reduces header loss by 2.12%. The soybean combine harvester reel speed control system designed in this article can realize automatic adjustment of the reel speed, reduce feeding losses caused by changes in crop height, changes in feed volume, and untimely adjustment of the reel, and can reduce header loss, increased crop yield.


Asunto(s)
Producción de Cultivos , Productos Agrícolas , Glycine max , Glycine max/crecimiento & desarrollo , Productos Agrícolas/crecimiento & desarrollo , Producción de Cultivos/métodos , Producción de Cultivos/instrumentación , Zea mays/crecimiento & desarrollo , Agricultura/métodos , Agricultura/instrumentación
2.
Environ Res ; 263(Pt 2): 120099, 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39374750

RESUMEN

Tetramethylammonium hydroxide (TMAH), an extensively utilized photoresist developer, is frequently present in ammonium-rich wastewater from semiconductor manufacturing, and its substantial ecotoxicity should not be underestimated. This study systematically investigated the effects of TMAH on the anammox granular sludge (AnGS) system and elucidated its inhibitory mechanisms. The results demonstrated that the median inhibitory concentration of TMAH for anammox was 84.85 mg/L. The nitrogen removal performance of the system was significantly decreased after long-term exposure to TMAH (0-200 mg/L) for 30 days (p < 0.05), but it showed adaptability to certain concentrations (≤50 mg/L). Concurrently, the stability of the granules decreased dramatically, resulting in the breakdown of AnGS. Further investigations indicated that TMAH exposure increased the secretion of extracellular polymeric substances but weakened their defense function. The increase in reactive oxygen species resulted in damage to the cell membrane. Reduced activity of anammox bacteria, impeded electron transfer, and changes in enzyme activity suggested that TMAH affected the metabolic activity. Microbiological analysis revealed that TMAH caused a decrease in the abundance of anammox bacteria and a weakening of symbiotic interactions within the microbial community. These results provide valuable guidance for the AnGS system application in chip wastewater treatment.

3.
Water Res ; 268(Pt A): 122617, 2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39405626

RESUMEN

Complete ammonia oxidation (comammox) bacteria have been detected in full-scale wastewater treatment plants. However, the slow growth rate limits the research and applications of comammox. Quorum sensing (QS) is an intercellular communication process to regulate microbial physiological metabolism, but its role in comammox Nitrospira has rarely been reported. In this study, denitrifying filter backwash, return and anoxic tank sludges were utilized as seeding inoculums to enrich comammox bacteria, with the addition of three types of signaling molecules (C6-HSL, C8-HSL and C12-HSL). Under ammonia- and dissolved oxygen (DO)-limited conditions, 12 lab-scale sequencing batch reactors (SBRs) were operated for 90 days. Quantitative polymerase chain reaction (qPCR) and 16S rRNA gene sequencing supported the enrichment of comammox Nitrospira in all SBRs. The highest absolute abundance of comammox Nitrospira amoA gene was detected in the anoxic tank sludge with exogenously added C8-HSL, reaching an average of 2.34×106 copies/(g sludge). In this condition, comammox Nitrospira and ammonia-oxidizing archaea contributed up to 94 % of the total nitrification activity, with ammonia-oxidizing bacteria accounting for only 6 %. Overall, the role of QS in comammox Nitrospira enrichment was confirmed, with signaling molecules significantly accelerating the growth of comammox Nitrospira, promoting functional enzyme activity, and strengthening nitrifying bacterial competitiveness. Among the signaling molecules tested, C8-HSL exhibited the most pronounced promotional effect, followed by C6-HSL and C12-HSL. Using anoxic tank sludge as the seed sludge with the addition of C8-HSL provides a rapid and reliable enrichment strategy for comammox Nitrospira. These findings offer insights into the role of QS in comammox bacteria enrichment, and might facilitate the development of biotechnologies for wastewater treatment based on comammox Nitrospira.

4.
Small ; : e2406001, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39263765

RESUMEN

Regulating the different growth states of polypyrrole (PPy) is a key strategy for obtaining PPy composites with high electromagnetic wave (EMW) absorption properties. This work finds that the growth states of PPy is regulated by controlling the amount of pyrrole added during the preparation of composites, so as to regulate the development of conductive networks to obtain excellent EMW absorption performance. The POP/PPy-200 composite achieves an effective absorption bandwidth (EAB) of 6.24 GHz (11.76-18.00 GHz) at a thickness of only 2.34 mm, covering 100% of the Ku band. The minimum reflection loss of -73.05 dB can be demonstrated at a thickness of only 2.29 mm, while at the same time showing an EAB of 5.96 GHz to meet the requirements of "thin", "light", "wide", and "strong". Such excellent EMW absorption performance is attributed to the conductive loss caused by the regulation of the growth states of PPy and the polarization loss caused by the heterostructure. This work also addresses the key challenge that porous organic polymers (POPs) cannot be applied to EMW absorption due to poor conductivity and providing new insights into the candidates for EMW absorbing materials.

5.
Expert Opin Drug Metab Toxicol ; : 1-9, 2024 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-39316645

RESUMEN

BACKGROUND: The gene polymorphisms of the CYP2C9, as well as the substrate specificity of the enzyme, result in different clearances for different substrates by CYP2C9 variants. RESEARCH DESIGNAND METHODS: The CYP2C9 wild type and 38 CYP2C9 variants, expressed in insectmicrosomes, were incubated with azilsartan. The resulting metabolite,O-desethyl azilsartan, was determined by HPLC-MS/MS. The enzyme kineticparameters of the 38 variants were calculated and compared with the wild type.Subsequently, we selected CYP2C9*1, *2, and *3 as target proteins for molecular docking with azilsartan to elucidate the mechanisms underlying changes in enzyme function. RESULTS: Compared with CYP2C9*1, three variants (CYP2C9*29, *39, and *49) exhibited markedlyincreased CLint values (from 170%-275%, *p < 0.05), whereas 28 variants exhibited significantly decreased CLint values (from 3-63%,*p < 0.05). The molecular docking results showed that the binding energy of CYP2C9*2 and *3 was lower than that of the wild type. CONCLUSION: Thisassessment revealed the effect of CYP2C9 gene polymorphisms on azilsartan metabolism, establishing a theoretical basis for further in-vivo studies and clinical applications. This study will help expand the database of CYP2C9 gene-drug pairs and identify appropriate treatment strategies for azilsartan, contributing to the field of precision medicine.

6.
Artículo en Inglés | MEDLINE | ID: mdl-39258657

RESUMEN

This systematic review and meta-analysis assessed the association between urinary tract infections (UTIs) during pregnancy and the risk of preterm birth (PTB). We searched multiple databases for relevant observational studies, categorizing them as UTI-based (comparing PTB incidence in women with and without UTIs) or PTB-based (comparing UTI prevalence in women with and without PTB). Using a random-effects model in Stata software version 17.0, we estimated pooled and adjusted odds ratios (ORs) with 95% confidence intervals (CIs), and performed subgroup, sensitivity, and cumulative analyses to explore heterogeneity. In total, 30 studies comprising 32 datasets were included, involving a total of 249,810 cases and 2,626,985 healthy controls. The meta-analysis revealed a significant positive association between UTIs during pregnancy and PTB occurrence (OR, 1.92; 95% CI, 1.62-2.27). A sub-group analysis based on studies, the participants showed significant association in both PTB-based (OR, 2.01; 95% CI, 1.58-2.56) and UTI-based studies (OR, 1.79; 95% CI, 1.42-2.26). However, Egger's test indicated the presence of publication bias (p=0.020), and substantial heterogeneity was observed across the included studies (I2=96.6; p< 0.001). These findings emphasize the critical importance of early detection and effective management of UTIs in pregnant women to reduce the risk of PTB and its associated adverse outcomes. While the results highlight a robust link between UTIs during pregnancy and PTB risk, the potential influence of publication bias and substantial heterogeneity should be considered to interpret these findings. Further research is needed to better understand the underlying mechanisms and to develop targeted interventions for high-risk pregnant women.


Asunto(s)
Complicaciones Infecciosas del Embarazo , Nacimiento Prematuro , Infecciones Urinarias , Femenino , Humanos , Embarazo , Incidencia , Complicaciones Infecciosas del Embarazo/epidemiología , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Prevalencia , Factores de Riesgo , Infecciones Urinarias/complicaciones , Infecciones Urinarias/epidemiología
7.
BMC Genomics ; 25(1): 851, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39261781

RESUMEN

BACKGROUND: The WD40 domain, one of the most abundant in eukaryotic genomes, is widely involved in plant growth and development, secondary metabolic biosynthesis, and mediating responses to biotic and abiotic stresses. WD40 repeat (WD40) protein has been systematically studied in several model plants but has not been reported in the Capsicum annuum (pepper) genome. RESULTS: Herein, 269, 237, and 257 CaWD40 genes were identified in the Zunla, CM334, and Zhangshugang genomes, respectively. CaWD40 sequences from the Zunla genome were selected for subsequent analysis, including chromosomal localization, phylogenetic relationships, sequence characteristics, motif compositions, and expression profiling. CaWD40 proteins were unevenly distributed on 12 chromosomes, encompassing 19 tandem duplicate gene pairs. The 269 CaWD40s were divided into six main branches (A to F) with 17 different types of domain distribution. The CaWD40 gene family exhibited diverse expression patterns, and several genes were specifically expressed in flowers and seeds. Yeast two-hybrid (Y2H) and dual-luciferase assay indicated that CaWD40-91 could interact with CaAN1 and CaDYT1, suggesting its involvement in anthocyanin biosynthesis and male sterility in pepper. CONCLUSIONS: In summary, we systematically characterized the phylogeny, classification, structure, and expression of the CaWD40 gene family in pepper. Our findings provide a valuable foundation for further functional investigations on WD40 genes in pepper.


Asunto(s)
Antocianinas , Capsicum , Filogenia , Proteínas de Plantas , Capsicum/genética , Capsicum/metabolismo , Antocianinas/biosíntesis , Antocianinas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genoma de Planta , Regulación de la Expresión Génica de las Plantas , Infertilidad Vegetal/genética , Repeticiones WD40/genética , Familia de Multigenes , Perfilación de la Expresión Génica , Cromosomas de las Plantas/genética
8.
Cell Death Dis ; 15(9): 663, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39256364

RESUMEN

The average five-year survival rate for esophageal cancer, a common malignant tumor of the digestive system, is barely 20%. The majority of esophageal squamous cell carcinoma (ESCC) patients had already progressed to a locally advanced or even advanced stage at initial diagnosis, making routine surgery ineffective. Chemotherapy and immunotherapy are important neoadjuvant treatments for ESCC, however, it remains unknown how treatment will affect the immunological microenvironment, especially at the spatial level. Here, we presented the TME characters of ESCC from the temporal and spatial dimensions using scRNA-seq and ST, investigated the changes of immune cell clusters in the TME under neoadjuvant chemotherapy and preoperative immunotherapy, and explored the potential mechanisms. It was found that compared with chemotherapy, immunotherapy combined with chemotherapy increased the level of T cell proliferation, partially restored the function of exhausted T cells, induced the expansion of specific exhausted CD8 T cells, increased the production of dendritic cells (DCs), and supported the immune hot microenvironment of the tumor. We also found that CD52 and ID3 have potential as biomarkers of ESCC. Particularly, CD52 may be served as a predictor of the efficacy to screen the advantaged population of different regimens. Through multiple pathways, CAF2 and CAF5's antigen-presenting role affected the other fibroblast clusters, resulting in malignant transformation. We analyzed the immune microenvironment differences between the two regimens to provide a more thorough description of the ESCC microenvironment profile and serve as a foundation for customized neoadjuvant treatment of ESCC.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Inmunoterapia , Terapia Neoadyuvante , Microambiente Tumoral , Humanos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/inmunología , Carcinoma de Células Escamosas de Esófago/inmunología , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/patología , Inmunoterapia/métodos , Masculino , Femenino
9.
Bioresour Technol ; 413: 131518, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39321941

RESUMEN

The use of immobilized microbial technology in wastewater treatment has drawn extensive attention due to its advantages of high colony density, rapid reaction speed, and good stability. Immobilization carriers are the core of immobilization technology. This review summarizes the types of immobilization carriers and their advantages and disadvantages, focusing on the potential for utilizing novel immobilization carriers (composite carriers, nanomaterials, metal-organic frameworks (MOFs), and biochar materials) in wastewater applications. The basic principles and technical advantages and disadvantages of novel immobilization methods (layer-by-layer self-assembly (LBL) and electrostatic spinning) are then summarized. Additionally, the research progress and application characteristics of immobilized anaerobic ammonia oxidizing (Anammox) and aerobic denitrifying (AD) bacteria for enhanced wastewater nitrogen removal are discussed. Finally, the current challenges of immobilized microbial technology are discussed, and its future development trends are summarized and prospected. This review provides guidance and theoretical support for the practical engineering application of immobilized microbial technology.


Asunto(s)
Aguas Residuales , Purificación del Agua , Aguas Residuales/química , Purificación del Agua/métodos , Bacterias/metabolismo , Células Inmovilizadas/metabolismo , Nitrógeno
10.
Nanoscale Adv ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39247870

RESUMEN

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer, characterized by aggressive malignancy and a poor prognosis. Emerging nanomedicine-based combination therapy represents one of the most promising strategies for combating TNBC. Polypyrrole nanoparticles (PPY) are excellent drug delivery vehicles with outstanding photothermal performances. However, the impact of morphology on PPY's drug loading efficiency and photothermal properties remains largely unexplored. In this study, we propose that pluronic P123 can assist in the synthesis of polypyrrole nanoparticles with rough surfaces (rPPY). During the synthesis, P123 formed small micelles around the nanoparticle surface, which were later removed, resulting in small pits and cavities in rPPY. Subsequently, the rPPY was loaded with the chemotherapy drug gemcitabine (Gem@rPPY) for chemo-photothermal therapy against TNBCs. Our results demonstrate that rPPY exhibited superior photothermal performance and significantly enhanced drug loading efficiency by five times compared to smooth PPY nanoparticles. In vitro assessments confirmed Gem@rPPY's robust photothermal properties by efficiently converting light into heat. Cell culture experiments with 4T1 cells and a TNBC mice model revealed significant tumor suppression upon Gem@rPPY administration, emphasizing its efficacy in inducing apoptosis. Toxicity evaluations demonstrated minimal adverse effects both in vitro and in vivo, highlighting the biocompatibility of Gem@rPPY. Overall, this study introduces a promising combination therapy nanoplatform that underscores the importance of surface engineering to enhance therapeutic outcomes and overcome current limitations in TNBC therapy.

11.
Medicine (Baltimore) ; 103(36): e38645, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39252228

RESUMEN

To evaluate the efficacy and postoperative complications of endoscopic thoracoscopic and laparoscopic radical esophagectomy compared to open surgery in esophageal cancer treatment. This retrospective study included 103 esophageal cancer patients admitted from August 2018 to March 2022, divided into observation (endoscopic surgery) and control (open surgery) groups. We compared intraoperative parameters, postoperative outcomes, immune function, and one-year overall survival (OS). Intraoperative bleeding volume, the retention time of chest tube, postoperative fasting time, and hospital stay in the observation group were smaller than those in the control group (P < .05). The differences were not statistically significant (P > .05) when comparing operative time, the number of intraoperative blood transfusion cases, and the rate of operating room extubation in these 2 groups. The differences were not statistically significant when comparing the amount of resected lymph nodes and the positive rate of incisal edge in these 2 groups (P > .05). There was no statistically significant difference in the complication rates such as pneumonia, pleural effusion, pneumothorax, pulmonary embolism, anastomotic fistula, the leakage of thoracic duct, the injury of RLN and arrhythmia in these 2 groups (P > .05). At 7 days postoperatively, the CD4+ and CD4+/CD8+ in the observation group and the control group were smaller than the preoperative ones in their same groups, and they were larger in the observation group than those in the control group (P < .05); There was no statistically significant difference on the CD8+ in the observation group and the control group at 7 days postoperatively compared with the preoperative ones in their same groups (P > .05). The 1-year postoperative OS rate was 81.63% (40/49) in the observation group and 72.22% (39/54) in the control group, and the difference was not statistically significant when comparing the OS rates of these 2 groups (P = .238, HR = 0.622, 95% CI = 0.279-1.385). Endoscopic thoracoscopic and laparoscopic esophagectomy offers less invasive treatment with significant short-term benefits and better preservation of immune function in esophageal cancer patients, making it a safe and effective surgical option.


Asunto(s)
Neoplasias Esofágicas , Esofagectomía , Laparoscopía , Complicaciones Posoperatorias , Toracoscopía , Humanos , Esofagectomía/métodos , Esofagectomía/efectos adversos , Neoplasias Esofágicas/cirugía , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Laparoscopía/métodos , Laparoscopía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Toracoscopía/métodos , Toracoscopía/efectos adversos , Anciano , Tempo Operativo , Resultado del Tratamiento , Tiempo de Internación/estadística & datos numéricos
12.
Medicine (Baltimore) ; 103(38): e39826, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39312340

RESUMEN

BACKGROUND: To assess the efficacy and safety of upadacitinib in adolescents with moderate-to-severe atopic dermatitis (AD). METHODS: A comprehensive search was conducted using PubMed, Medline, Embase, Web of Science, Clinical Trials Website, and Cochrane Library databases, spanning from their inception until February 18, 2024. The review incorporated all randomized controlled trials examining upadacitinib's efficacy in managing moderate to severe AD among adolescent patients. The methodological quality of the selected studies underwent thorough assessment utilizing the Cochrane systematic review methodology. Statistical analyses of the outcome measures were executed employing the Review Manager 5.3 software. RESULTS: The meta-analysis encompassed 4 studies in total. Compared to placebo, upadacitinib at doses of both 15 and 30 mg was associated with a significant enhancement in the eczema area and severity index-75% ([odds ratio, OR = 11.06, 95% confidence interval, CI (6.78-18.04), P < .00001]; [OR = 21.73, 95% CI (12.73-37.11), P < .00001]), a reduction in the numerical rating scale of ≥4 ([OR = 6.16, 95% CI (3.56-10.64), P < .00001]; [OR = 10.58, 95% CI (6.12-18.29), P < .00001]), and improvement in the investigator's global assessment to 0/1 ([OR = 8.85, 95% CI (4.86-16.10), P < .00001]; [OR = 21.43, 95% CI (11.64-39.46), P < .00001]). Regarding safety, upadacitinib at both 15 and 30 mg doses was linked to a statistically significant rise in the overall incidence of adverse events when juxtaposed with placebo ([OR = 1.57, 95% CI (1.01-2.44), P = .04]; [OR = 2.21, 95% CI (1.44-3.41), P = .0003]). Nevertheless, no statistically significant disparity was discovered in the occurrence of serious adverse events between upadacitinib and placebo ([OR = 1.02, 95% CI (0.27-3.84), P = .98]; [OR = 0.42, 95% CI (0.09-1.93), P = .26]). CONCLUSION: The findings from this meta-analysis indicate that upadacitinib demonstrates substantial effectiveness and tolerability in treating moderate to severe AD in adolescents. Moreover, upadacitinib provides a rapid reduction in pruritus and markedly ameliorates symptoms and signs, with the 30 mg dosage showing a more pronounced therapeutic effect relative to the 15 mg dosage.


Asunto(s)
Dermatitis Atópica , Compuestos Heterocíclicos con 3 Anillos , Adolescente , Femenino , Humanos , Masculino , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Compuestos Heterocíclicos con 3 Anillos/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
13.
Neural Netw ; 179: 106574, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39096754

RESUMEN

Graph neural networks (GNN) are widely used in recommendation systems, but traditional centralized methods raise privacy concerns. To address this, we introduce a federated framework for privacy-preserving GNN-based recommendations. This framework allows distributed training of GNN models using local user data. Each client trains a GNN using its own user-item graph and uploads gradients to a central server for aggregation. To overcome limited data, we propose expanding local graphs using Software Guard Extension (SGX) and Local Differential Privacy (LDP). SGX computes node intersections for subgraph exchange and expansion, while local differential privacy ensures privacy. Additionally, we introduce a personalized approach with Prototype Networks (PN) and Model-Agnostic Meta-Learning (MAML) to handle data heterogeneity. This enhances the encoding abilities of the federated meta-learner, enabling precise fine-tuning and quick adaptation to diverse client graph data. We leverage SGX and local differential privacy for secure parameter sharing and defense against malicious servers. Comprehensive experiments across six datasets demonstrate our method's superiority over centralized GNN-based recommendations, while preserving user privacy.


Asunto(s)
Redes Neurales de la Computación , Privacidad , Seguridad Computacional , Humanos , Programas Informáticos , Aprendizaje Automático , Algoritmos
14.
Clin Transl Med ; 14(8): e1738, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39095323

RESUMEN

BACKGROUND: The therapeutic potential of immune checkpoint blockade (ICB) extends across various cancers; however, its effectiveness in treating hepatocellular carcinoma (HCC) is frequently curtailed by both inherent and developed resistance. OBJECTIVE: This research explored the effectiveness of integrating anlotinib (a broad-spectrum tyrosine kinase inhibitor) with programmed death-1 (PD-1) blockade and offers mechanistic insights into more effective strategies for treating HCC. METHODS: Using patient-derived organotypic tissue spheroids and orthotopic HCC mouse models, we assessed the effectiveness of anlotinib combined with PD-1 blockade. The impact on the tumour immune microenvironment and underlying mechanisms were assessed using time-of-flight mass cytometry, RNA sequencing, and proteomics across cell lines, mouse models, and HCC patient samples. RESULTS: The combination of anlotinib with an anti-PD-1 antibody enhanced the immune response against HCC in preclinical models. Anlotinib remarkably suppressed the expression of transferrin receptor (TFRC) via the VEGFR2/AKT/HIF-1α signaling axis. CD8+ T-cell infiltration into the tumour microenvironment correlated with low expression of TFRC. Anlotinib additionally increased the levels of the chemokine CXCL14, crucial for attracting CD8+ T cells. CXCL14 emerged as a downstream effector of TFRC, exhibiting elevated expression following the silencing of TFRC. Importantly, low TFRC expression was also associated with a better prognosis, enhanced sensitivity to combination therapy, and a favourable response to anti-PD-1 therapy in patients with HCC. CONCLUSIONS: Our findings highlight anlotinib's potential to augment the efficacy of anti-PD-1 immunotherapy in HCC by targeting TFRC and enhancing CXCL14-mediated CD8+ T-cell infiltration. This study contributes to developing novel therapeutic strategies for HCC, emphasizing the role of precision medicine in oncology. HIGHLIGHTS: Synergistic effects of anlotinib and anti-PD-1 immunotherapy demonstrated in HCC preclinical models. Anlotinib inhibits TFRC expression via the VEGFR2/AKT/HIF-1α pathway. CXCL14 upregulation via TFRC suppression boosts CD8+ T-cell recruitment. TFRC emerges as a potential biomarker for evaluating prognosis and predicting response to anti-PD-1-based therapies in advanced HCC patients.


Asunto(s)
Linfocitos T CD8-positivos , Carcinoma Hepatocelular , Inmunoterapia , Indoles , Neoplasias Hepáticas , Quinolinas , Receptores de Transferrina , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/inmunología , Quinolinas/farmacología , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Animales , Ratones , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Indoles/farmacología , Indoles/uso terapéutico , Humanos , Inmunoterapia/métodos , Receptores de Transferrina/metabolismo , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/metabolismo , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología
15.
Cancer Lett ; 601: 217178, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39142497

RESUMEN

Tertiary lymphoid structures (TLSs) were associated with survival in esophageal squamous cell carcinoma (ESCC) undergoing surgery alone (SA). However, their clinical relevance in neoadjuvant therapies remains less known. Here, we firstly investigated the presence, maturation and spatial distribution of TLSs in 359 ESCC patients receiving neoadjuvant chemotherapy (NCT), neoadjuvant immunotherapy (NCI), neoadjuvant chemoradiotherapy (NCRT) or SA. We found mature TLS (MTLS) was an independent prognostic factor in ESCC. NCI group had the lowest immature TLS cases. NCRT group had the lowest MTLSs. MTLSs mostly located in stromal and normal compartments; these MTLSs were positively correlated with neoadjuvant therapy outcomes. NCI group displayed the highest T cells within 150 µm proximity of TLSs among the four groups. Most T cells were dispersed up to more than 150 µm from TLSs, while B cells remained concentrated within TLSs. Innate lymphoid cells and follicular dendritic cells infiltrated and connected with survival differently in NCRT and NCI groups compared with SA group. The novel PD-L1 combined positive score, NCPS, was positively connected with MTLSs and neoadjuvant therapy efficacy. ScRNA-seq analysis revealed TLS+ tumors had increased plasma cells, B cells, Th17, Tfh and Th1, and elevated exhausted CD8+ T cells that highly expressed checkpoint molecules and granzymes. Conclusively, MTLSs favored treatment outcome in ESCC patients receiving multiple neoadjuvant therapies. The spatial distribution of MTLSs was associated with multiregional immune status modified by the neoadjuvant therapies.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Terapia Neoadyuvante , Estructuras Linfoides Terciarias , Humanos , Terapia Neoadyuvante/métodos , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/inmunología , Carcinoma de Células Escamosas de Esófago/genética , Estructuras Linfoides Terciarias/inmunología , Estructuras Linfoides Terciarias/patología , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/inmunología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Pronóstico , Inmunoterapia/métodos , Microambiente Tumoral/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo
16.
Mol Cell ; 84(19): 3758-3774.e10, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39127036

RESUMEN

N6-methyladenosine (m6A) modification is deemed to be co-transcriptionally installed on pre-mRNAs, thereby influencing various downstream RNA metabolism events. However, the causal relationship between m6A modification and RNA processing is often unclear, resulting in premature or even misleading generalizations on the function of m6A modification. Here, we develop 4sU-coupled m6A-level and isoform-characterization sequencing (4sU-m6A-LAIC-seq) and 4sU-GLORI to quantify the m6A levels for both newly synthesized and steady-state RNAs at transcript and single-base-resolution levels, respectively, which enable dissecting the relationship between m6A modification and alternative RNA polyadenylation. Unexpectedly, our results show that many m6A addition events occur post-transcriptionally, especially on transcripts with high m6A levels. Importantly, we find higher m6A levels on shorter 3' UTR isoforms, which likely result from sequential polyadenylation of longer 3' UTR isoforms with prolonged nuclear dwelling time. Therefore, m6A modification can also take place post-transcriptionally to intimately couple with other key RNA metabolism processes to establish and dynamically regulate epi-transcriptomics in mammalian cells.


Asunto(s)
Adenosina , Núcleo Celular , Poliadenilación , Procesamiento Postranscripcional del ARN , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina/genética , Humanos , Núcleo Celular/metabolismo , Núcleo Celular/genética , Regiones no Traducidas 3' , ARN Mensajero/metabolismo , ARN Mensajero/genética , Células HEK293 , Metiltransferasas/metabolismo , Metiltransferasas/genética , Células HeLa , Animales
17.
Int J Surg ; 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39110573

RESUMEN

BACKGROUND: This study aimed to use artificial intelligence (AI) to integrate various radiological and clinical pathological data to identify effective predictors of contralateral cervical lymph node metastasis (CCLNM) in patients with papillary thyroid carcinoma (PTC) and to establish a clinically applicable model to guide the extent of surgery. METHODS: This prospective cohort study included 603 patients with PTC from three centers. Clinical, pathological, and ultrasonographic data were collected and utilized to develop a machine learning (ML) model for predicting CCLNM. Model development at the internal center utilized logistic regression along with other ML algorithms. Diagnostic efficacy was compared among these methods, leading to the adoption of the final model (random forest). This model was subject to AI interpretation and externally validated at other centers. RESULTS: CCLNM was associated with multiple pathological factors. The Delphian lymph node metastasis ratio, ipsilateral cervical lymph node metastasis number, and presence of ipsilateral cervical lymph node metastasis were independent risk factors for CCLNM. Following feature selection, a Delphian lymph node-CCLNM (D-CCLNM) model was established using the Random forest algorithm based on five attributes. The D-CCLNM model demonstrated the highest area under the curve (AUC; 0.9273) in the training cohort and exhibited high predictive accuracy, with AUCs of 0.8907 and 0.9247 in the external and validation cohorts, respectively. CONCLUSIONS: We developed a new, effective method that uses ML to predict CCLNM in patients with PTC. This approach integrates data from Delphian lymph nodes and clinical characteristics, offering a foundation for guiding surgical decisions, and is conveniently applicable in clinical settings.

18.
BMC Plant Biol ; 24(1): 746, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39098914

RESUMEN

BACKGROUND: The male sterile lines are an important foundation for heterosis utilization in wheat (Triticum aestivum L.). Thereinto, pollen development is one of the indispensable processes of wheat reproductive development, and its fertility plays an important role in wheat heterosis utilization, and are usually influencing by genes. However, these key genes and their regulatory networks during pollen abortion are poorly understood in wheat. RESULTS: DEFECTIVE IN TAPETAL DEVELOPMENT AND FUNCTION 1 (TDF1) is a member of the R2R3-MYB family and has been shown to be essential for early tapetal layer development and pollen grain fertility in rice (Oryza sativa L.) and Arabidopsis thaliana. In order to clarify the function of TDF1 in wheat anthers development, we used OsTDF1 gene as a reference sequence and homologous cloned wheat TaTDF1 gene. TaTDF1 is localized in the nucleus. The average bolting time of Arabidopsis thaliana overexpressed strain (TaTDF1-OE) was 33 d, and its anther could be colored normally by Alexander staining solution, showing red. The dominant Mosaic suppression silence-line (TaTDF1-EAR) was blue-green in color, and the anthers were shrimpy and thin. The TaTDF1 interacting protein (TaMAP65) was confirmed using Yeast Two-Hybrid Assay (Y2H) and Bimolecular-Fluorescence Complementation (BiFC) experiments. The results showed that downregulated expression of TaTDF1 and TaMAP65 could cause anthers to be smaller and shrunken, leading to pollen abortion in TaTDF1 wheat plants induced by virus-induced gene-silencing technology. The expression pattern of TaTDF1 was influenced by TaMAP65. CONCLUSIONS: Thus, systematically revealing the regulatory mechanism of wheat TaTDF1 during anther and pollen grain development may provide new information on the molecular mechanism of pollen abortion in wheat.


Asunto(s)
Infertilidad Vegetal , Proteínas de Plantas , Polen , Triticum , Triticum/genética , Triticum/fisiología , Infertilidad Vegetal/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Polen/genética , Polen/crecimiento & desarrollo , Arabidopsis/genética , Arabidopsis/fisiología , Regulación de la Expresión Génica de las Plantas , Plantas Modificadas Genéticamente/genética , Flores/genética , Flores/crecimiento & desarrollo , Flores/fisiología , Genes de Plantas
19.
Phytomedicine ; 133: 155944, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39146879

RESUMEN

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) remains a significant challenge in cancer therapy, especially due to its resistance to established treatments like Gemcitabine, necessitating novel therapeutic approaches. METHODS: This study utilized Gemcitabine-resistant cell lines, patient-derived organotypic tumor spheroids (PDOTs), and patient-derived xenografts (PDX) to evaluate the effects of Saikosaponin-a (SSA) on ICC cellular proliferation, migration, apoptosis, and its potential synergistic interaction with Gemcitabine. Techniques such as transcriptome sequencing, Luciferase reporter assays, and molecular docking were employed to unravel the molecular mechanisms. RESULTS: SSA exhibited antitumor effects in both in vitro and PDX models, indicating its considerable potential for ICC treatment. SSA markedly inhibited ICC progression by reducing cellular proliferation, enhancing apoptosis, and decreasing migration and invasion. Crucially, it augmented Gemcitabine's efficacy by targeting the p-AKT/BCL6/ABCA1 signaling pathway. This modulation led to the downregulation of p-AKT and suppression of BCL6 transcriptional activity, ultimately reducing ABCA1 expression and enhancing chemosensitivity to Gemcitabine. Additionally, ABCA1 was validated as a predictive biomarker for drug resistance, with a direct correlation between ABCA1 expression levels and the IC50 values of various small molecule drugs in ICC gene profiles. CONCLUSION: This study highlights the synergistic potential of SSA combined with Gemcitabine in enhancing therapeutic efficacy against ICC and identifies ABCA1 as a key biomarker for drug responsiveness. Furthermore, the introduction of the novel PDOTs microfluidic model provides enhanced insights into ICC research. This combination strategy may provide a novel approach to overcoming treatment challenges in ICC.


Asunto(s)
Transportador 1 de Casete de Unión a ATP , Neoplasias de los Conductos Biliares , Colangiocarcinoma , Desoxicitidina , Resistencia a Antineoplásicos , Gemcitabina , Ácido Oleanólico , Proteínas Proto-Oncogénicas c-akt , Saponinas , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Ácido Oleanólico/farmacología , Ácido Oleanólico/análogos & derivados , Saponinas/farmacología , Colangiocarcinoma/tratamiento farmacológico , Humanos , Línea Celular Tumoral , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Transportador 1 de Casete de Unión a ATP/metabolismo , Ratones , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Sinergismo Farmacológico , Ensayos Antitumor por Modelo de Xenoinjerto
20.
Zhongguo Gu Shang ; 37(8): 801-7, 2024 Aug 25.
Artículo en Chino | MEDLINE | ID: mdl-39183005

RESUMEN

OBJECTIVE: To investigate global optimisation of anterior acetabular column pinning channels can be achieved based on large density point cloud data. METHODS: Data were collected on the CT scans of the normal pelvis in 40 adults from January 2022 to January 2023, including 22 males and 18 females, aged 20 to 54 years old. Medical imaging data from three of the samples were selected for experimental study. In planning access for anterior acetabular column pinning, to address the issue of whether the current CAD planning methods were advanced or not, four combinations of the same point cloud acquisition channels, different directional line creation software, and the same 3D design and virtual experiment software were proposed: Mimics+Imageware+UG, Mimics+3DReshaper+UG, Mimics+ZEISS Quality Suite+UG and Mimics+Design X+UG, and directional lines created based on the centroid point set and solid point cloud of the secondary pruning model, respectively, and it applied to the planning of the left anterior column pinning channel of the three acetabular samples. The maximum internally connected cylinder without acetabular socket and pubic bone penetration was used as a safe passage for nailing of the anterior acetabular column to evaluate the advancement of each method. RESULTS: The fitting effect of the directional line was better than that of the unnoised solid point cloud when the central point set with obvious relevant features was selected as the sample points;and the combination of Mimics+Imageware+UG and Mimics+3DReshaper+UG could efficiently and stably obtain the desirable planning results when planning with the central point set, respectively, in the three acetabular samples 1, 2, 3. The maximum internal joint circle diameters obtained in samples 1, 2, and 3 were 10.35 mm, 9.62 mm, and 9.24 mm;and when the directional lines were based on the solid point cloud the combined methods of Mimics+ZEISS Quality Suite+UG and Mimics+Design X+UG were not applicable;whereas the Mimics+3DReshaper+UG the solid point cloud denoising planning method could stably obtain the maximum value of the safe channel for nail placement, and the maximum internal joint circle diameters obtained in acetabular samples 1, 2, and 3 are 10.66 mm, 10.96 mm, and 9.48 mm, respectively. CONCLUSION: It is recommended that the nail placement channel planners use robust Mimics+Imageware+UG or Mimics+3DReshaper+UG centre point set planning method, and if there is enough time, it is recommended to use the solid point cloud denoising planning method of Mimics+3DReshaper+UG in order to obtain the maximum value of safe channels for nail placement.


Asunto(s)
Acetábulo , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Acetábulo/cirugía , Acetábulo/diagnóstico por imagen , Clavos Ortopédicos , Tomografía Computarizada por Rayos X , Adulto Joven
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