Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 109
Filtrar
1.
Sensors (Basel) ; 24(17)2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39275679

RESUMO

Accurately obtaining the geological characteristic digital model of a coal seam and surrounding rock in front of a fully mechanized mining face is one of the key technologies for automatic and continuous coal mining operation to realize an intelligent unmanned working face. The research on how to establish accurate and reliable coal seam digital models is a hot topic and technical bottleneck in the field of intelligent coal mining. This paper puts forward a construction method and dynamic update mechanism for a digital model of coal seam autonomous cutting by a coal mining machine, and verifies its effectiveness in experiments. Based on the interpolation model of drilling data, a fine coal seam digital model was established according to the results of geological statistical inversion, which overcomes the shortcomings of an insufficient lateral resolution of lithology and physical properties in a traditional geological model and can accurately depict the distribution trend of coal seams. By utilizing the numerical derivation of surrounding rock mining and geological SLAM advanced exploration, the coal seam digital model was modified to achieve a dynamic updating and optimization of the model, providing an accurate geological information guarantee for intelligent unmanned coal mining. Based on the model, it is possible to obtain the boundary and inclination information of the coal seam profile, and provide strategies for adjusting the height of the coal mining machine drum at the current position, achieving precise control of the automatic height adjustment of the coal mining machine.

2.
Phys Rev Lett ; 133(5): 056001, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39159112

RESUMO

The natural bulk Van der Waals heterostructure compound 6R-TaS_{2} consists of alternate stacking 1T- and 1H-TaS_{2} monolayers, creating a unique system that incorporates charge-density-wave (CDW) order and superconductivity (SC) in distinct monolayers. Here, after confirming that the 2D nature of the lattice is preserved up to 8 GPa in 6R-TaS_{2}, we documented an unusual evolution of CDW and SC by conducting high-pressure electronic transport measurements. Upon compression, we observe a gradual suppression of CDW within the 1T layers, while the SC exhibits a dome-shaped behavior that terminates at a critical pressure P_{c} around 2.9 GPa. By taking account of the fact that the substantial suppression of SC is concomitant with the complete collapse of CDW order at P_{c}, we argue that the 6R-TaS_{2} behaves like a stack of Josephson junctions and thus the suppressed superconductivity can be attributed to the weakening of Josephson coupling associated with the presence of CDW fluctuations in the 1T layers. Furthermore, the SC reversely enhances above P_{c}, implying the development of emergent superconductivity in the 1T layers after the melting of T-layer CDW orders. These results show that the 6R-TaS_{2} not only provides a promising platform to explore emergent phenomena but also serves as a model system to study the complex interactions between competing electronic states.

3.
Plants (Basel) ; 13(15)2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39124187

RESUMO

Lemon, as an important cash crop with rich nutritional value, holds significant cultivation importance and market demand worldwide. However, lemon diseases seriously impact the quality and yield of lemons, necessitating their early detection for effective control. This paper addresses this need by collecting a dataset of lemon diseases, consisting of 726 images captured under varying light levels, growth stages, shooting distances and disease conditions. Through cropping high-resolution images, the dataset is expanded to 2022 images, comprising 4441 healthy lemons and 718 diseased lemons, with approximately 1-6 targets per image. Then, we propose a novel model lemon surface disease YOLO (LSD-YOLO), which integrates Switchable Atrous Convolution (SAConv) and Convolutional Block Attention Module (CBAM), along with the design of C2f-SAC and the addition of a small-target detection layer to enhance the extraction of key features and the fusion of features at different scales. The experimental results demonstrate that the proposed LSD-YOLO achieves an accuracy of 90.62% on the collected datasets, with mAP@50-95 reaching 80.84%. Compared with the original YOLOv8n model, both mAP@50 and mAP@50-95 metrics are enhanced. Therefore, the LSD-YOLO model proposed in this study provides a more accurate recognition of healthy and diseased lemons, contributing effectively to solving the lemon disease detection problem.

4.
Microb Pathog ; 195: 106816, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39032675

RESUMO

Salmonella is a zoonotic pathogen posing a serious risk to the farming industry and public health due to food animals serving as reservoirs for future contamination and spread of Salmonella. The present study is designed to monitor the contamination status of Salmonella in duck farms and the main control points during breeding. 160 strains of duck-derived Salmonella were isolated from the 736 samples (cloacal swabs, feces, water, feed, soil, air and dead duck embryos) collected in southwest Shandong Province and the province's surrounding area. The percentage of Salmonella-positive samples collected was 21.74 % (160/736), and the greatest prevalence from duck embryo samples (40.00 %, 36/90). These Salmonella were classified into 23 serotypes depending on their O and H antigens, in which S. Typhimurium (30.15 %), S. Kottbus (13.97 %) and S. Enteritidis (10.29 %) were the prevailing serotypes. Subsequently, the molecular subtyping was done. Clustered regularly interspaced short palindromic repeats (CRISPR) analysis showed that 41 strains of S. Typhimurium and 14 strains of S. Enteritidis were classified into 13 and 3 genotypes, respectively. 19 S. Kottbus isolates from different sources featured ST1546, ST198, ST321, and ST1690 by multilocus sequence typing (MLST) analysis, among which ST1546 belongs to S. Kottbus was a new ST. The minimum spanning tree analysis based on the two CRISPR loci and seven MLST loci from all S. Typhimurium, S. Enteritidis and S. Kottbus isolates revealed that duck embryos, feed and water were key control points to the spread of Salmonella along the breeding chain. Meanwhile, the emergence of S. Kottbus in duck flocks was considered a potential public health hazard.


Assuntos
Patos , Fazendas , Fezes , Genótipo , Doenças das Aves Domésticas , Salmonelose Animal , Salmonella , Sorogrupo , Animais , Patos/microbiologia , China/epidemiologia , Salmonelose Animal/microbiologia , Salmonelose Animal/epidemiologia , Salmonella/genética , Salmonella/isolamento & purificação , Salmonella/classificação , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/epidemiologia , Fezes/microbiologia , Salmonella typhimurium/genética , Salmonella typhimurium/isolamento & purificação , Salmonella typhimurium/classificação , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , Prevalência , Filogenia , Salmonella enteritidis/genética , Salmonella enteritidis/isolamento & purificação , Salmonella enteritidis/classificação , Tipagem de Sequências Multilocus , Sorotipagem
5.
J Refract Surg ; 40(7): e453-e459, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39007816

RESUMO

PURPOSE: To compare the prediction accuracy of the Barrett toric calculator using standard or integrated keratometry (IK) mode in combination with predicted or measured posterior corneal astigmatism (PCA) in a group of patients with cataract implanted with non-toric IOLs. METHODS: In this retrospective clinical cohort study, the medical records of patients with age-related cataract who underwent phacoemulsification with the implantation of an aspheric monofocal IOL were reviewed. Four methods, including standard keratometry with predicted PCA (PPCA), IK combined with predicted PCA (IK-PPCA), and IK combined with measured PCA derived from IOLMaster 700 (Carl Zeiss Meditec AG) or CASIA2 (Tomey) (IK-MMPCA or IK-CMPCA), were applied to the Barrett toric calculator to calculate the predicted residual astigmatism. The mean absolute prediction error (MAPE), centroid of the prediction error, and proportion of eyes within the prediction error of ±0.50, ±0.75, and ±1.00 diopters (D) were all ciphered out from the four methods, respectively. RESULTS: Data from 129 eyes of 129 patients were included in this study. The MAPE of the IK-PPCA method (0.57 ± 0.36 D) was significantly smaller than that of the PPCA (0.62 ± 0.38 D) and IK-CMPCA (0.63 ± 0.46 D) methods (P = .048 and .014, respectively). There were no significant differences in the centroid vectors of prediction errors and predictability rates among the four methods (all P > .05). CONCLUSIONS: In the current version of the Barrett toric calculator, the predictive accuracy of the IK mode incorporating PPCA was slightly superior to using the standard keratometry mode or incorporating MPCA. [J Refract Surg. 2024;40(7):e453-e459.].


Assuntos
Astigmatismo , Córnea , Facoemulsificação , Humanos , Astigmatismo/fisiopatologia , Astigmatismo/diagnóstico , Estudos Retrospectivos , Masculino , Feminino , Idoso , Córnea/fisiopatologia , Córnea/patologia , Reprodutibilidade dos Testes , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Implante de Lente Intraocular , Acuidade Visual/fisiologia , Topografia da Córnea/métodos , Refração Ocular/fisiologia , Lentes Intraoculares , Pseudofacia/fisiopatologia
6.
J Environ Qual ; 53(4): 456-469, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38872314

RESUMO

Phosphorus (P) that accumulates in agricultural riparian zones can be released under certain hydrological and biogeochemical conditions, thereby limiting the effectiveness of these zones in reducing P loads from field to stream. The study objective was to explore factors that may be contributing to, or limiting, high soluble reactive phosphorus (SRP) concentrations in the shallow aquifer of an alluvial upland riparian zone located in a continental climate. Field investigations including porewater sampling from six vertical nests, soil sampling, and continuous soil moisture, groundwater table, and redox measurements were conducted over 19 months. Porewater SRP concentrations were generally low in the aquifer considering all sampling times (median = 14.7 µg/L; interquartile range [IQR] = 11.1 µg/L, 287 samples). The overall low SRP may be due to low reducible labile soil P (median = 21.1 µgP/g dw, IQR = 10.9 µgP/g dw, 21 samples). However, high SRP concentrations (>52 µg/L, 95% quartile) did occur intermittently in space and time with no clear spatial or temporal patterns. Analyses indicate that most high concentrations were likely not associated with factors previously reported to influence SRP release in riparian aquifers, including redox conditions, pH, and soil drying and wetting. Further, data indicate that internally released or externally supplied SRP may undergo rapid (re-) sequestration within the aquifer, limiting its vertical or horizontal transport. The study findings highlight the complexity of P behavior in riparian zones and the need for caution when assessing the effectiveness of conservation practices and in interpreting potential impacts of subsurface water quality on stream water quality when monitoring locations are distant from the stream.


Assuntos
Monitoramento Ambiental , Água Subterrânea , Fósforo , Poluentes Químicos da Água , Fósforo/análise , Água Subterrânea/química , Água Subterrânea/análise , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química , Hidrologia , Solo/química , Rios/química
7.
Technol Health Care ; 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38759072

RESUMO

BACKGROUND: The etiology of Burning Mouth Syndrome (BMS) remains unclear. OBJECTIVE: To explore the differences in the therapeutic efficacy of pain improvement between medication therapy and laser therapy in patients with BMS. METHODS: 45 BMS patients were randomly divided into three groups: The Combination therapy group (Group A, n= 15), The Medication therapy group (Group B, n= 15), and the Laser therapy group (Group C, n= 15). The pain condition of the patients was evaluated using the Numeric Rating Scale (NRS), and the improvement in pain before and after treatment was compared among the three groups. RESULTS: All three groups (A, B, and C) showed a significant reduction in NRS scores after treatment, with statistically significant differences observed among the different groups. Group A exhibited the most significant improvement, with a statistically significant difference before and after treatment. CONCLUSION: Laser and medication therapy are effective methods for reducing oral burning pain * symptoms, and their combined use yields more significant therapeutic effects.

8.
Technol Health Care ; 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38759078

RESUMO

BACKGROUND: The etiology of Burning Mouth Syndrome (BMS) remains unclear. OBJECTIVE: To explore the differences in the therapeutic efficacy of pain improvement between medication therapy and laser therapy in patients with BMS. METHODS: 45 BMS patients were randomly divided into three groups: The Combination therapy group (Group A, n= 15), The Medication therapy group (Group B, n= 15), and the Laser therapy group (Group C, n= 15). The pain condition of the patients was evaluated using the Numeric Rating Scale (NRS), and the improvement in pain before and after treatment was compared among the three groups. RESULTS: All three groups (A, B, and C) showed a significant reduction in NRS scores after treatment, with statistically significant differences observed among the different groups. Group A exhibited the most significant improvement, with a statistically significant difference before and after treatment. CONCLUSION: Laser and medication therapy are effective methods for reducing oral burning pain * symptoms, and their combined use yields more significant therapeutic effects.

9.
PLoS One ; 19(5): e0301317, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38696407

RESUMO

With the predicament of sustainable improvement in traditional cities, the low-carbon city pilot policy (LCCPP), as a novel development mode, provides thinking for resolving the tensions of green development, resource conservation and environmental protection among firms. Using Chinese A-share listed companies panel data during 2007-2019, this study adopts the difference-in-differences model to explore the impact of LCCPP on firm green innovation. Based on theoretical analysis, LCCPP-driven environmental rules have the impact of encouraging business green innovation. The relationship between LCCPP and green innovation is strengthened by external media attention and organizational redundancy resources. The mechanism study shows that the incentive effect of LCCPP on firm green innovation is mainly due to the improvement of enterprises' green total factor productivity and financial stability. In addition, the heterogeneity analysis shows that the LCCPP has significantly positive effects in promoting green innovation in high-carbon industries and state-owned enterprises. This research contributes to the understanding of city-level low-carbon policies as a driving force for corporate green innovation, offering practical implications for policymakers and businesses striving for sustainability.


Assuntos
Carbono , Cidades , Desenvolvimento Sustentável , China , Desenvolvimento Sustentável/economia , Projetos Piloto , Conservação dos Recursos Naturais/métodos , Conservação dos Recursos Naturais/economia , Humanos
11.
Nano Lett ; 24(10): 3204-3212, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38416569

RESUMO

The flicker frequency of incident light constitutes a critical determinant in biology. Nevertheless, the exploration of methods to simulate external light stimuli with varying frequencies and develop artificial retinal neurons capable of responsive behavior remains an open question. This study presents an artificial neuron comprising organic phototransistors. The triggering properties of neurons are modulated by optical input, enabling them to execute rudimentary synaptic functions, emulating the biological characteristics of retinal neurons. The artificial retinal neuron exhibits varying responses to incoming light frequencies, allowing it to replicate the persistent visual behavior of the human eye and facilitating image discrimination. Additionally, through seamless integration with circuitry, it can execute motion recognition on a machine cart, preventing collisions with high-speed obstacles. The artificial retinal neuron offers a cost-effective and energy-efficient route for future mobile robot processors.


Assuntos
Retina , Visão Ocular , Humanos , Neurônios/fisiologia
12.
Cell Mol Life Sci ; 81(1): 57, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38279052

RESUMO

The Wnt/ß-catenin pathway is critical to maintaining cell fate decisions. Recent study showed that liquid-liquid-phase separation (LLPS) of Axin organized the ß-catenin destruction complex condensates in a normal cellular state. Mutations inactivating the APC gene are found in approximately 80% of all human colorectal cancer (CRC). However, the molecular mechanism of the formation of ß-catenin destruction complex condensates organized by Axin phase separation and how APC mutations impact the condensates are still unclear. Here, we report that the ß-catenin destruction complex, which is constructed by Axin, was assembled condensates via a phase separation process in CRC cells. The key role of wild-type APC is to stabilize destruction complex condensates. Surprisingly, truncated APC did not affect the formation of condensates, and GSK 3ß and CK1α were unsuccessfully recruited, preventing ß-catenin phosphorylation and resulting in accumulation in the cytoplasm of CRCs. Besides, we propose that the phase separation ability of Axin participates in the nucleus translocation of ß-catenin and be incorporated and concentrated into transcriptional condensates, affecting the transcriptional activity of Wnt signaling pathway.


Assuntos
Complexo de Sinalização da Axina , beta Catenina , Humanos , Complexo de Sinalização da Axina/genética , Proteína Axina/genética , Proteína Axina/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Separação de Fases , Mutação/genética , Via de Sinalização Wnt/genética , Proteína da Polipose Adenomatosa do Colo/genética , Proteína da Polipose Adenomatosa do Colo/metabolismo
13.
Cancer Res Treat ; 56(2): 602-615, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37846469

RESUMO

PURPOSE: Patients with advanced biliary tract cancer (BTC) have a poor survival. We aim to evaluate the efficacy and safety of nab-paclitaxel plus gemcitabine and cisplatin regimen in Chinese advanced BTC patients. MATERIALS AND METHODS: Eligible patients with locally advanced or metastatic BTC administrated intravenous 100 mg/m2 nab-paclitaxel, 800 mg/m2 gemcitabine, and 25 mg/m2 cisplatin every 3 weeks. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and adverse events, while exploratory endpoint was the association of biomarkers with efficacy. RESULTS: After the median follow-up of 25.0 months, the median PFS and OS of 34 enrolled patients were 7.1 months (95% confidence interval [CI], 5.4 to 13.7) and 16.4 months (95% CI, 10.9 to 23.6), respectively. The most common treatment-related adverse events at ≥ 3 grade were neutropenia (26.5%) and leukopenia (26.5%). Survival analyses demonstrated that carcinoembryonic antigen (CEA) levels could monitor patients' survival outcomes. A significant increase in the number of infiltrating CD4+ cells (p=0.008) and a decrease in programmed death-1-positive (PD-1+) cells (p=0.032) were observed in the response patients. CONCLUSION: In advanced BTC patients, nab-paclitaxel plus gemcitabine and cisplatin regimen showed therapeutic potential. Potential prognostic factors of CEA levels, number of CD4+ cells and PD-1+ cells may help us maximize the efficacy benefit.


Assuntos
Albuminas , Neoplasias dos Ductos Biliares , Paclitaxel , Neoplasias Pancreáticas , Humanos , Gencitabina , Cisplatino/efeitos adversos , Desoxicitidina/efeitos adversos , Antígeno Carcinoembrionário/uso terapêutico , Receptor de Morte Celular Programada 1 , Neoplasias dos Ductos Biliares/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Pancreáticas/patologia
14.
J Mol Cell Biol ; 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37791390

RESUMO

Meningioma is one of the most common primary neoplasms in the central nervous system, whereas there is still no specific molecularly targeted therapy that has been approved for the clinical treatment of aggressive meningiomas. There is therefore an urgent demand to decrypt the biological and molecular landscape of malignant meningioma. Here, through the in-silica prescreening and 10-year follow-up of 445 meningioma patients, we uncovered that CBX7 is progressively decreased with malignancy grade and neoplasia stage in meningioma and a high CBX7 expression level predicts a favorable prognosis in meningioma patients. CBX7 restoration significantly induces cell cycle arrest and inhibits meningioma cell proliferation. iTRAQ-based proteomics analysis indicated that CBX7 restoration triggers the metabolic shift from glycolysis to oxidative phosphorylation. The mechanistic study demonstrated that CBX7 promotes the proteasome-dependent degradation of c-MYC proteins by transcriptionally inhibiting the expression of a c-MYC deubiquitinase, USP44, which attenuates c-MYC-mediated transactivation of LDHA transcripts and further inhibits glycolysis and subsequent cellular proliferation. More importantly, the functional role of CBX7 was further confirmed in both subcutaneous and orthotopic meningioma xenografts mouse models and human meningioma patients. Together, our results shed light on the critical role of CBX7 during meningioma malignancy progression and identified the CBX7/USP44/c-MYC/LDHA axis as a promising therapeutic target against meningioma progression.

15.
Proc Natl Acad Sci U S A ; 120(42): e2219589120, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37812694

RESUMO

NTRK (neurotrophic tyrosine receptor kinase) gene fusions that encode chimeric proteins exhibiting constitutive activity of tropomyosin receptor kinases (TRK), are oncogenic drivers in multiple cancer types. However, the underlying mechanisms in oncogenesis that involve various N-terminal fusion partners of NTRK fusions remain elusive. Here, we show that NTRK fusion proteins form liquid-like condensates driven by their N-terminal fusion partners. The kinase reactions are accelerated in these condensates where the complexes for downstream signaling activation are also concentrated. Our work demonstrates that the phase separation driven by NTRK fusions is not only critical for TRK activation, but the condensates formed through phase separation serve as organizational hubs for oncogenic signaling.


Assuntos
Neoplasias , Proteínas de Fusão Oncogênica , Humanos , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Transdução de Sinais/genética , Neoplasias/genética , Neoplasias/metabolismo , Fusão Gênica , Receptor trkA/genética , Receptor trkA/metabolismo , Inibidores de Proteínas Quinases
16.
Cell Death Dis ; 14(9): 581, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37658049

RESUMO

Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an RNA-binding protein, is associated with tumorigenesis and progression. However, the exact molecular mechanisms of IGF2BP3 in colorectal cancer (CRC) oncogenesis, progression, and drug resistance remain unclear. This study found that IGF2BP3 was upregulated in CRC tissues. Clinically, the elevated IGF2BP3 level is predictive of a poor prognosis. Functionally, IGF2BP3 enhances CRC tumorigenesis and progression both in vitro and in vivo. Mechanistically, IGF2BP3 promotes epidermal growth factor receptor (EGFR) mRNA stability and translation and further activates the EGFR pathway by serving as a reader in an N6-methyladenosine (m6A)-dependent manner by cooperating with METTL14. Furthermore, IGF2BP3 increases the drug resistance of CRC cells to the EGFR-targeted antibody cetuximab. Taken together, our results demonstrated that IGF2BP3 was a functional and clinical oncogene of CRC. Targeting IGF2BP3 and m6A modification may therefore offer rational therapeutic targets for patients with CRC.


Assuntos
Neoplasias Colorretais , Receptores ErbB , Humanos , Anticorpos , Carcinogênese , Transformação Celular Neoplásica , Cetuximab , RNA Mensageiro
17.
Microbiol Spectr ; : e0018923, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37655887

RESUMO

Gut microbiota and their secreted metabolites have an influence on the initiation and progression of colon cancer. Probiotics are extensively perceived as a potential microbiota-modulation strategy to promote the health of the host, while the effectiveness of preventing colon cancer based on microbiota therapy has not been confirmed, and antitumor mechanisms influenced by microbiota and their metabolites with the intervention of probiotics remain to be further investigated. In vitro, Lactobacillus (JY300-8 and JMR-01) significantly inhibited the proliferation of CT26, HT29, and HCT116 cells. Moreover, we studied the prevention and therapy efficiency of Lactobacillus and its underlying antitumor mechanism through the alteration of gut microbiota and their metabolites regulated by Lactobacillus in colon cancer models in mice. We demonstrated that the pre-administration of Lactobacillus (JY300-8 and JMR-01) for 20 days before establishing tumor models resulted in an 86.21% reduction in tumor formation rate compared to tumor control group. Subsequently, continuous oral administration of living Lactobacillus significantly suppresses tumor growth, and tumor volumes decrease by 65.2%. Microbiome and metabolome analyses reveal that Lactobacillus suppresses colonic tumorigenesis and progression through the modulation of gut microbiota homeostasis and metabolites, including the down-regulation of secondary bile acids, sphingosine 1-phosphate (S1P), and pyrimidine metabolism, as well as the production of anticarcinogenic compounds in tumor-bearing mice. Additionally, metabolome analyses of Lactobacillus (JY300-8 and JMR-01) indicate that living Lactobacillus could reduce the relative abundance of alanine and L-serine to suppress tumor progression by regulating the tumor microenvironment, including down-regulation of pyrimidine metabolism and S1P signaling in cancer. These findings provide a potential prevention strategy and therapeutic target for colon cancer through the intervention of dietary Lactobacillus. IMPORTANCE The modulation of gut microbiota and metabolites has a significant influence on the progression of colon cancer. Our research indicated that the intervention of probiotics is a potentially feasible strategy for preventing colon cancer. We have also revealed the underlying antitumor mechanism through the alteration of gut microbiota and their metabolites, which could lead to broader biomedical impacts on the prevention and therapy of colon cancer with microbiota-based therapy regulated by probiotics.

18.
Oncogene ; 42(38): 2841-2853, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37591954

RESUMO

Proficient mismatch repair or microsatellite stable (pMMR/MSS) colorectal cancers (CRCs) are vastly outnumbered by deficient mismatch repair or microsatellite instability-high (dMMR/MSI-H) tumors and lack a response to immune checkpoint inhibitors (ICIs). In this study, we reported two distinct expression patterns of ASCL2 in pMMR/MSS and dMMR/MSI-H CRCs. ASCL2 is overexpressed in pMMR/MSS CRCs and maintains a stemness phenotype, accompanied by a lower density of tumor-infiltrating lymphocytes (TILs) than those in dMMR/MSI CRCs. In addition, coadministration of anti-PD-L1 antibodies facilitated T cell infiltration and provoked strong antitumor immunity and tumor regression in the MC38/shASCL2 mouse CRC model. Furthermore, overexpression of ASCL2 was associated with increased TGFB levels, which stimulate local Cancer-associated fibroblasts (CAFs) activation, inducing an immune-excluded microenvironment. Consistently, mice with deletion of Ascl2 specifically in the intestine (Villin-Cre+, Ascl2 flox/flox, named Ascl2 CKO) revealed fewer activated CAFs and higher proportions of infiltrating CD8+ T cells; We further intercrossed Ascl2 CKO with ApcMin/+ model suggesting that Ascl2-deficient expression in intestinal represented an immune infiltrating environment associated with a good prognosis. Together, our findings indicated ASCL2 induces an immune excluded microenvironment by activating CAFs through transcriptionally activating TGFB, and targeting ASCL2 combined with ICIs could present a therapeutic opportunity for MSS CRCs.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias do Colo , Neoplasias Colorretais , Animais , Camundongos , Linfócitos T CD8-Positivos , Neoplasias Colorretais/genética , Modelos Animais de Doenças , Instabilidade de Microssatélites , Repetições de Microssatélites
19.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 52(2): 243-248, 2023 Apr 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-37283110

RESUMO

The application of artificial neural network algorithm in pathological diagnosis of gastrointestinal malignant tumors has become a research hotspot. In the previous studies, the algorithm research mainly focused on the model development based on convolutional neural networks, while only a few studies used the combination of convolutional neural networks and recurrent neural networks. The research contents included classical histopathological diagnosis and molecular typing of malignant tumors, and the prediction of patient prognosis by utilizing artificial neural networks. This article reviews the research progress on artificial neural network algorithm in the pathological diagnosis and prognosis prediction of digestive tract malignant tumors.


Assuntos
Neoplasias Gastrointestinais , Redes Neurais de Computação , Humanos , Algoritmos , Prognóstico , Neoplasias Gastrointestinais/diagnóstico
20.
Int J Radiat Biol ; 99(5): 779-790, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36731457

RESUMO

BACKGROUND: Probiotics such as Lactobacillus could modulate the intestinal microbiota and have been considered as an effective strategy for ameliorating colon carcinoma. Nevertheless, its efficiency remains the biggest challenge. METHODS: We investigated the therapeutic efficacy of Lactobacillus reuteri JMR-01 adjuvant 12C6+ irradiation on CT-26 syngeneic mouse models. Meanwhile, intestinal flora and innate immunity were examined to outline mechanisms. RESULTS: Anti-proliferation effect of live probiotic combined with inactivated probiotic JMR-01 (LP + IP) on CT-26 reached a maximum of 39.55% among other experiment groups at 24 h when the ratio of cell to CFU was 1:1 in vitro. These activities have been fully validated in vivo, tumor-bearing mice treated by 12C6+ irradiation combining with living and inactivated probiotics JMR-01 (IR + LP + IP) for 50-day held the highest survival rate (71.4%) and complete remission rate (14.3%). We also demonstrated significant fluctuation in gut microbiota, including the decreased abundance of Bacteroides fragilis and Clostridium perfringens related to tumorigenesis and development, and the increased abundance of Lactobacillus and Bifidobacterium closely associated with health restoration in fecal of mice treated with JMR-01 LP + IP adjuvant 12C6+ irradiation (IR + LP + IP). Similarly, the decreasing nitroreductase activities and increasing short chain fatty acids (SCFAs) concentrations were observed in IR + LP + IP group compared with tumor control group, which further confirmed the changes of gut microbiota. Additionally, we found that the strongest stimulation index of splenocyte (2.47) and the phagocytosis index peritoneal macrophage (3.68) were achieved by LP + IP compared with single live JMR-01 (LP) and inactivated JMR-01 (IP). CONCLUSIONS: JMR-01 LP + IP adjuvant 12C6+ irradiation could mitigate cancer progression by modulating innate immunity as well as intestinal flora.


Assuntos
Carcinoma , Neoplasias do Colo , Microbioma Gastrointestinal , Limosilactobacillus reuteri , Animais , Camundongos , Lactobacillus , Neoplasias do Colo/radioterapia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA