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2.
Sensors (Basel) ; 24(12)2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38931735

RESUMO

Autonomous exploration in unknown environments is a fundamental problem for the practical application of unmanned ground vehicles (UGVs). However, existing exploration methods face difficulties when directly applied to UGVs due to limited sensory coverage, conservative exploration strategies, inappropriate decision frequencies, and the non-holonomic constraints of wheeled vehicles. In this paper, we present IB-PRM, a hierarchical planning method that combines Incremental B-splines with a probabilistic roadmap, which can support rapid exploration by a UGV in complex unknown environments. We define a new frontier structure that includes both information-gain guidance and a B-spline curve segment with different arrival orientations to satisfy the non-holonomic constraint characteristics of UGVs. We construct and maintain local and global graphs to generate and store filtered frontiers. By jointly solving the Traveling Salesman Problem (TSP) using these frontiers, we obtain the optimal global path traversing feasible frontiers. Finally, we optimize the global path based on the Time Elastic Band (TEB) algorithm to obtain a smooth, continuous, and feasible local trajectory. We conducted comparative experiments with existing advanced exploration methods in simulation environments of different scenarios, and the experimental results demonstrate that our method can effectively improve the efficiency of UGV exploration.

4.
Acta Pharmacol Sin ; 45(6): 1264-1275, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38438582

RESUMO

In addition to the classical resistance mechanisms, receptor tyrosine-protein kinase AXL is a main mechanism of resistance to third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) osimertinib in EGFR-mutated non-small cell lung cancer (NSCLC). Developing an effective AXL inhibitor is important to sensitize osimertinib in clinical application. In this study we assessed the efficacy of brigatinib, a second-generation of anaplastic lymphoma kinase (ALK)-TKI, as a novel AXL inhibitor, in overcoming acquired resistance to osimertinib induced by AXL activation. We established an AXL-overexpression NSCLC cell line and conducted high-throughput screening of a small molecule chemical library containing 510 anti-tumor drugs. We found that brigatinib potently inhibited AXL expression, and that brigatinib (0.5 µM) significantly enhanced the anti-tumor efficacy of osimertinib (1 µM) in AXL-mediated osimertinib-resistant NSCLC cell lines in vitro. We demonstrated that brigatinib had a potential ability to bind AXL kinase protein and further inhibit its downstream pathways in NSCLC cell lines. Furthermore, we revealed that brigatinib might decrease AXL expression through increasing K48-linked ubiquitination of AXL and promoting AXL degradation in HCC827OR cells and PC-9OR cells. In AXL-high expression osimertinib-resistant PC-9OR and HCC827OR cells derived xenograft mouse models, administration of osimertinib (10 mg·kg-1·d-1) alone for 3 weeks had no effect, and administration of brigatinib (25 mg·kg-1·d-1) alone caused a minor inhibition on the tumor growth; whereas combination of osimertinib and brigatinib caused marked tumor shrinkages. We concluded that brigatinib may be a promising clinical strategy for enhancing osimertinib efficacy in AXL-mediated osimertinib-resistant NSCLC patients.


Assuntos
Acrilamidas , Compostos de Anilina , Antineoplásicos , Receptor Tirosina Quinase Axl , Carcinoma Pulmonar de Células não Pequenas , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB , Neoplasias Pulmonares , Camundongos Nus , Compostos Organofosforados , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas , Pirimidinas , Receptores Proteína Tirosina Quinases , Animais , Feminino , Camundongos , Acrilamidas/farmacologia , Acrilamidas/uso terapêutico , Compostos de Anilina/farmacologia , Compostos de Anilina/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Indóis , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Camundongos Endogâmicos BALB C , Mutação , Compostos Organofosforados/farmacologia , Compostos Organofosforados/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
5.
New Phytol ; 242(5): 2043-2058, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38515251

RESUMO

MicroRNAs are essential in plant development and stress resistance, but their specific roles in drought stress require further investigation. Here, we have uncovered that a Populus-specific microRNAs (miRNA), miR6445, targeting NAC (NAM, ATAF, and CUC) family genes, is involved in regulating drought tolerance of poplar. The expression level of miR6445 was significantly upregulated under drought stress; concomitantly, seven targeted NAC genes showed significant downregulation. Silencing the expression of miR6445 by short tandem target mimic technology significantly decreased the drought tolerance in poplar. Furthermore, 5' RACE experiments confirmed that miR6445 directly targeted NAC029. The overexpression lines of PtrNAC029 (OE-NAC029) showed increased sensitivity to drought compared with knockout lines (Crispr-NAC029), consistent with the drought-sensitive phenotype observed in miR6445-silenced strains. PtrNAC029 was further verified to directly bind to the promoters of glutathione S-transferase U23 (GSTU23) and inhibit its expression. Both Crispr-NAC029 and PtrGSTU23 overexpressing plants showed higher levels of PtrGSTU23 transcript and GST activity while accumulating less reactive oxygen species (ROS). Moreover, poplars overexpressing GSTU23 demonstrated enhanced drought tolerance. Taken together, our research reveals the crucial role of the miR6445-NAC029-GSTU23 module in enhancing poplar drought tolerance by regulating ROS homeostasis. This finding provides new molecular targets for improving the drought resistance of trees.


Assuntos
Adaptação Fisiológica , Secas , Regulação da Expressão Gênica de Plantas , Glutationa Transferase , MicroRNAs , Proteínas de Plantas , Populus , Espécies Reativas de Oxigênio , Populus/genética , Populus/fisiologia , Populus/enzimologia , MicroRNAs/genética , MicroRNAs/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Adaptação Fisiológica/genética , Plantas Geneticamente Modificadas , Estresse Fisiológico/genética , Sequestradores de Radicais Livres/metabolismo , Sequência de Bases , Genes de Plantas , Regiões Promotoras Genéticas/genética , Resistência à Seca
6.
Microorganisms ; 11(12)2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38138060

RESUMO

Tausonia pullulans 6A7 is a low-temperature yeast strain that can produce lipases. Yeast, which is made up of chassis cells, is an important part of synthetic biology, and the use of the lipase-producing properties of T. pullulans 6A7 for the production of fatty acids provides a new pathway for targeted synthesis in yeast cell factories. In this study, we performed RNA-seq on lipase-producing T. pullulans 6A7 at different temperatures (15 °C, 20 °C, 20 °C without corn oil, and 25 °C). Therefore, a total of 8455 differentially expressed genes were screened, and 16 of them were FAD candidate genes. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of group A (15 °C) vs. group D (25 °C) showed that the pathways of fatty acid biosynthesis (map00061) and the biosynthesis of unsaturated fatty acids (map01040) were significantly enriched. In the proposed temporal analysis of differentially expressed genes among the four temperature modulations, we found differentially expressed genes in nine clusters that had the same expression trends; these genes may be jointly involved in multiple biological processes in T. pullulans 6A7. In addition, we found 16 FAD candidate genes involved in fatty acid biosynthesis, and the expression of these genes had similar expression in the transcriptome trends with the different temperature treatments. These findings will help in future in-depth studies of the function and molecular mechanisms of these important FAD genes involved in fatty acid metabolism in yeast, and they could also be conducive to the establishment of a cellular factory for targeted fatty acid production by using yeast.

7.
BMC Genomics ; 24(1): 473, 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37605104

RESUMO

BACKGROUND: Drought stress is a prevalent abiotic stress that significantly hinders the growth and development of plants. According to studies, ß-aminobutyric acid (BABA) can influence the ABA pathway through the AtIBI1 receptor gene to enhance cold resistance in Arabidopsis. However, the Aspartate tRNA-synthetase (AspRS) gene family, which acts as the receptor for BABA, has not yet been investigated in poplar. Particularly, it is uncertain how the AspRS gene family (PtrIBIs)r can resist drought stress after administering various concentrations of BABA to poplar. RESULTS: In this study, we have identified 12 AspRS family genes and noted that poplar acquired four PtrIBI pairs through whole genome duplication (WGD). We conducted cis-action element analysis and found a significant number of stress-related action elements on different PtrIBI genes promoters. The expression of most PtrIBI genes was up-regulated under beetle and mechanical damage stresses, indicating their potential role in responding to leaf damage stress. Our results suggest that a 50 mM BABA treatment can alleviate the damage caused by drought stress in plants. Additionally, via transcriptome sequencing, we observed that the partial up-regulation of BABA receptor genes, PtrIBI2/4/6/8/11, in poplars after drought treatment. We hypothesize that poplar responds to drought stress through the BABA-PtrIBIs-PtrVOZ coordinated ABA signaling pathway. Our research provides molecular evidence for understanding how plants respond to drought stress through external application of BABA. CONCLUSIONS: In summary, our study conducted genome-wide analysis of the AspRS family of P. trichocarpa and identified 12 PtrIBI genes. We utilized genomics and bioinformatics to determine various characteristics of PtrIBIs such as chromosomal localization, evolutionary tree, gene structure, gene doubling, promoter cis-elements, and expression profiles. Our study found that certain PtrIBI genes are regulated by drought, beetle, and mechanical damage implying their crucial role in enhancing poplar stress tolerance. Additionally, we observed that external application of low concentrations of BABA increased plant drought resistance under drought stress. Through the BABA-PtrIBIs-PtrVOZ signaling module, poplar plants were able to transduce ABA signaling and regulate their response to drought stress. These results suggest that the PtrIBI genes in poplar have the potential to improve drought tolerance in plants through the topical application of low concentrations of BABA.


Assuntos
Arabidopsis , Aspartato-tRNA Ligase , Besouros , Animais , Resistência à Seca , Transdução de Sinais/genética , Arabidopsis/genética , RNA de Transferência/genética
8.
ChemSusChem ; 16(23): e202300699, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-37561115

RESUMO

Electrochemical conversion of alkanes to high value-added oxygenated products under a mild condition is of significance. Herein, we effectively couple the electrocatalysis of H2 O2 with the thermo-catalysis of propane oxidation in the cathode of proton exchange membrane fuel cell. Specifically, H2 O2 is in-situ generated on the nitric acid-treated carbon black (C-acid) via 2e- process of oxygen reduction reaction, and then transports to the Fe active sites of MIL-53 (Al, Fe) metal-organic frameworks for propane oxidation. Based on this strategy, the space-time yield of C3 oxygenated products of propane oxidation reaches 2.65 µmol h-1 cm-2 , which represents a new benchmark for electrochemical alkane oxidation in the fuel-cell-type electrolyzer. This study highlights the importance of multifunctional composite catalysts in the field of electrosynthesis.

9.
Sensors (Basel) ; 23(14)2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37514595

RESUMO

When the magnitude of a gaze is too large, human beings change the orientation of their head or body to assist their eyes in tracking targets because saccade alone is insufficient to keep a target at the center region of the retina. To make a robot gaze at targets rapidly and stably (as a human does), it is necessary to design a body-head-eye coordinated motion control strategy. A robot system equipped with eyes and a head is designed in this paper. Gaze point tracking problems are divided into two sub-problems: in situ gaze point tracking and approaching gaze point tracking. In the in situ gaze tracking state, the desired positions of the eye, head and body are calculated on the basis of minimizing resource consumption and maximizing stability. In the approaching gaze point tracking state, the robot is expected to approach the object at a zero angle. In the process of tracking, the three-dimensional (3D) coordinates of the object are obtained by the bionic eye and then converted to the head coordinate system and the mobile robot coordinate system. The desired positions of the head, eyes and body are obtained according to the object's 3D coordinates. Then, using sophisticated motor control methods, the head, eyes and body are controlled to the desired position. This method avoids the complex process of adjusting control parameters and does not require the design of complex control algorithms. Based on this strategy, in situ gaze point tracking and approaching gaze point tracking experiments are performed by the robot. The experimental results show that body-head-eye coordination gaze point tracking based on the 3D coordinates of an object is feasible. This paper provides a new method that differs from the traditional two-dimensional image-based method for robotic body-head-eye gaze point tracking.


Assuntos
Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Movimentos Oculares , Movimentos Sacádicos , Fixação Ocular , Movimentos da Cabeça , Retina
10.
Foods ; 12(11)2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37297380

RESUMO

We have successfully identified the transcription factor Cmr1 from the fungus Aureobasidium pullulans Hit-lcy3T, which regulates melanin biosynthesis genes. Bioinformatics analysis revealed that the Cmr1 gene encodes a protein of 945 amino acids, containing two Cys2His2 zinc finger domains and a Zn(II)2Cys6 binuclear cluster domain located at the N-terminus of Cmr1. To investigate the function of the Cmr1 gene, we performed gene knockout and overexpression experiments. Our results showed that Cmr1 is a key regulator of melanin synthesis in Hit-lcy3T, and its absence caused developmental defects. Conversely, overexpression of Cmr1 significantly increased the number of chlamydospores in Hit-lcy3T and improved melanin production. RT-qPCR analysis further revealed that overexpression of Cmr1 enhanced the expression of several genes involved in melanin biosynthesis, including Cmr1, PKS, SCD1, and THR1. Melanin extracted from the Hit-lcy3T was characterized using UV and IR spectroscopy. Furthermore, we assessed the antioxidant properties of Hit-lcy3T melanin and found that it possesses strong scavenging activity against DPPH·, ABTS·, and OH·, but weaker activity against O2-·. These findings suggest that Hit-lcy3T melanin holds promise for future development as a functional food additive.

11.
Int J Biol Macromol ; 242(Pt 2): 124797, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37182631

RESUMO

pH is one of the important environmental factors affecting the growth, development and secondary metabolites of fungi. To better utilize potato waste for the production of pullulan by fermentation, in this study, the amino acid sequence and structural domain of pH transcription factor Appacc were analyzed using the bioinformatics methods. Appacc showed three typically conserved zinc finger domains, with the closest homology to Zymoseptoria brevis. The function of Appacc was characterized by ΔAppacc and OEXpacc mutants. The mycelium growth of ΔApacc mutants was inhibited, especially, under alkaline conditions. Furthermore, the pullulan production of ΔAppacc mutant was reduced and the expression of pullulan synthetic genes also decreased. Moreover, the OEXpacc mutant further demonstrated that pacc could regulate the expression of pullulan synthesis genes. The yield of pullulan polysaccharide increased from 13.6 g/L to 17.8 g/L by direct fermentation without changing the pH of potato waste. These results suggest that Appacc played a vital role in the growth of Aureobasidium pullulans and that the production of pullulan from potato waste can be increased by overexpression of pacc gene.


Assuntos
Solanum tuberosum , Solanum tuberosum/genética , Regulação para Cima , Fatores de Transcrição/genética , Fermentação , Concentração de Íons de Hidrogênio
12.
Opt Express ; 31(7): 11142-11155, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-37155756

RESUMO

Single-photon devices such as switches, beam splitters, and circulators are fundamental components to construct photonic integrated quantum networks. In this paper, two V-type three-level atoms coupled to a waveguide are proposed to simultaneously realize these functions as a multifunctional and reconfigurable single-photon device. When both the two atoms are driven by the external coherent fields, the difference in the phases of the coherent driving induces the photonic Aharonov-Bohm effect. Based on the photonic Aharonov-Bohm effect and setting the two-atom distance to match the constructive or destructive interference conditions among photons travelling along different paths, a single-photon switch is achieved since the incident single photon can be controlled from complete transmission to complete reflection by adjusting the amplitudes and phases of the driving fields. When properly changing the amplitudes and phases of the driving fields, the incident photons are split equally into multiple components as a beam splitter operated with different frequencies. Meanwhile, the single-photon circulator with reconfigurable circulation directions can also be obtained.

13.
Chin J Traumatol ; 26(3): 155-161, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37019724

RESUMO

PURPOSE: This study aims to elucidate the electrotaxis response of alveolar epithelial cells (AECs) in direct-current electric fields (EFs), explore the impact of EFs on the cell fate of AECs, and lay the foundation for future exploitation of EFs for the treatment of acute lung injury. METHODS: AECs were extracted from rat lung tissues using magnetic-activated cell sorting. To elucidate the electrotaxis responses of AECs, different voltages of EFs (0, 50, 100, and 200 mV/mm) were applied to two types of AECs, respectively. Cell migrations were recorded and trajectories were pooled to better demonstrate cellular activities through graphs. Cell directionality was calculated as the cosine value of the angle formed by the EF vector and cell migration. To further demonstrate the impact of EFs on the pulmonary tissue, the human bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B cells) were obtained and experimented under the same conditions as AECs. To determine the influence on cell fate, cells underwent electric stimulation were collected to perform Western blot analysis. RESULTS: The successful separation and culturing of AECs were confirmed through immunofluorescence staining. Compared with the control, AECs in EFs demonstrated a significant directionality in a voltage-dependent way. In general, type Ⅰ alveolar epithelial cells migrated faster than type Ⅱ alveolar epithelial cells, and under EFs, these two types of cells exhibited different response threshold. For type Ⅱ alveolar epithelial cells, only EFs at 200 mV/mm resulted a significant difference to the velocity, whereas for, EFs at both 100 mV/mm and 200 mV/mm gave rise to a significant difference. Western blotting suggested that EFs led to an increased expression of a AKT and myeloid leukemia 1 and a decreased expression of Bcl-2-associated X protein and Bcl-2-like protein 11. CONCLUSION: EFs could guide and accelerate the directional migration of AECs and exert antiapoptotic effects, which indicated that EFs are important biophysical signals in the re-epithelialization of alveolar epithelium in lung injury.


Assuntos
Células Epiteliais Alveolares , Lesão Pulmonar , Humanos , Ratos , Animais , Pulmão , Movimento Celular/fisiologia
14.
Int J Mol Sci ; 24(5)2023 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-36902250

RESUMO

F-box proteins are important components of eukaryotic SCF E3 ubiquitin ligase complexes, which specifically determine protein substrate proteasomal degradation during plant growth and development, as well as biotic and abiotic stress. It has been found that the FBA (F-box associated) protein family is one of the largest subgroups of the widely prevalent F-box family and plays significant roles in plant development and stress response. However, the FBA gene family in poplar has not been systematically studied to date. In this study, a total of 337 F-box candidate genes were discovered based on the fourth-generation genome resequencing of P. trichocarpa. The domain analysis and classification of candidate genes revealed that 74 of these candidate genes belong to the FBA protein family. The poplar F-box genes have undergone multiple gene replication events, particularly in the FBA subfamily, and their evolution can be attributed to genome-wide duplication (WGD) and tandem duplication (TD). In addition, we investigated the P. trichocarpa FBA subfamily using the PlantGenIE database and quantitative real-time PCR (qRT-PCR); the results showed that they are expressed in the cambium, phloem and mature tissues, but rarely expressed in young leaves and flowers. Moreover, they are also widely involved in the drought stress response. At last, we selected and cloned PtrFBA60 for physiological function analysis and found that it played an important role in coping with drought stress. Taken together, the family analysis of FBA genes in P. trichocarpa provides a new opportunity for the identification of P. trichocarpa candidate FBA genes and elucidation of their functions in growth, development and stress response, thus demonstrating their utility in the improvement of P. trichocarpa.


Assuntos
Proteínas F-Box , Família Multigênica , Secas , Genoma de Planta , Genes de Plantas , Proteínas F-Box/genética , Estresse Fisiológico/genética , Filogenia , Proteínas de Plantas/genética , Regulação da Expressão Gênica de Plantas
15.
Foods ; 12(3)2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36766189

RESUMO

The ability of the fungus to regulate metabolism on various nitrogen sources makes it survive and metabolize in different environments. The biomass and the ß-glucan yield of Aureobasidium pullulans are closely associated with the nitrogen source. This study found the only GATA nitrogen source activation regulating factor Area in HIT-LCY3. In order to testify the Area function, we amplified its conserved domain to build a silencing vector and used the RNAi to obtain the Area silent strain, and then explored its effect on the phenotype of A. pullulans and the yield of ß-glucan. We found that the biomass and ß-glucan yield of the silent strain decreased significantly after culturing with different nitrogen sources, in particular when using sodium nitrate and glutamate as the source. However, the ß-glucan yield increased significantly after overexpression of Area, reaching 5.2 g/L when glutamine was the nitrogen source. In addition, the strain morphology changed as well under different nitrogen sources. At last, we investigated the antioxidant activity in vitro of ß-glucan and found that it has a significant clearance effect on OH·, DPPH·, and ABTS·, being best with ABTS. Therefore, this study believed that the Area gene has a certain regulation function on the synthesis of ß-glucan with antioxidant activity.

16.
Neoplasma ; 70(1): 114-122, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36704921

RESUMO

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors with a low quality of life. Because traditional surgical treatment often causes large wounds and then affects the quality of life of patients, it is urgent to find new and efficient drugs with good safety for clinical treatment. This study aimed to identify potential anticancer drugs starting from the traditional Chinese medicine Salvia miltiorrhiza extract. Cryptotanshinone, a compound isolated from the Chinese herb Salvia miltiorrhiza, was found to significantly induce apoptosis and inhibit proliferation in OSCC. By electron microscopy, autophagosomes were found. Confocal fluorescence microscopy data showed that cryptotanshinone significantly induced autophagy in OSCC cells. Mechanistically, the western blot assay indicated that cryptotanshinone induced cell autophagy through the activation of the LC3 pathway, whereas the autophagy inhibitor 3-methyladenine attenuated these effects. Furthermore, we demonstrated that cryptotanshinone had a significant antitumor effect in a tumor xenograft model, and no damage to vital organs was observed. Our findings provide evidence that cryptotanshinone may be a novel therapeutic strategy for the treatment of OSCC.


Assuntos
Antineoplásicos , Carcinoma de Células Pequenas , Medicamentos de Ervas Chinesas , Neoplasias Bucais , Humanos , Masculino , Adulto , Fenantrenos/uso terapêutico , Neoplasias Bucais/tratamento farmacológico , Autofagia , Antineoplásicos/farmacologia , Carcinoma de Células Pequenas/tratamento farmacológico , Qualidade de Vida
17.
Chinese Journal of Oncology ; (12): 621-626, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-984758

RESUMO

Objective: To evaluate the effect of depth of remission of induction chemotherapy on the overall prognosis of limited stage small cell lung cancer (L-SCLC). Methods: The study was a retrospective, L-SCLC patients who contained complete imaging data and underwent consecutive standardized treatments at the Department of Thoracic Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University between January 2013 and June 2021 were included. To delineate the volume of tumor before and after induction chemotherapy and to calculate the depth of remission caused by the induced chemotherapy. The time receiver operating characteristic (timeROC) method was used to determine the optimal predictors for prognosis, multi-factor analysis using Cox risk proportional model. Results: A total of 104 patients were included in this study. The median PFS and OS of this cohort were 13.7 months and 20.9 months, respectively. It was observed by timeROC analysis that residual tumor volume after induction chemotherapy had the optimal predictive value of PFS at 1 year (AUC=0.86, 95% CI: 0.78~0.94) and OS at 2 years (AUC=0.76, 95% CI: 0.65~0.87). Multivariate analysis showed residual tumor volume after induction chemotherapy was the independent prognostic factor to PFS (HR=1.006, 95% CI: 1.003~1.009, P<0.01) and OS (HR=1.009, 95% CI: 1.005~1.012, P<0.001). For those whose residual tumor volume remitted to less than 10 cm(3) after induction chemotherapy, the favorable long-term outcomes could be achieved, regardless of their initial tumor load. Conclusion: The depth of remission of induction chemotherapy could be a promising prognostic predictor to the L-SCLC and provide the individualized treatment guidance.


Assuntos
Humanos , Carcinoma de Pequenas Células do Pulmão/patologia , Neoplasias Pulmonares/patologia , Quimioterapia de Indução , Estudos Retrospectivos , Neoplasia Residual , Prognóstico
18.
Chinese Journal of Traumatology ; (6): 155-161, 2023.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-981928

RESUMO

PURPOSE@#This study aims to elucidate the electrotaxis response of alveolar epithelial cells (AECs) in direct-current electric fields (EFs), explore the impact of EFs on the cell fate of AECs, and lay the foundation for future exploitation of EFs for the treatment of acute lung injury.@*METHODS@#AECs were extracted from rat lung tissues using magnetic-activated cell sorting. To elucidate the electrotaxis responses of AECs, different voltages of EFs (0, 50, 100, and 200 mV/mm) were applied to two types of AECs, respectively. Cell migrations were recorded and trajectories were pooled to better demonstrate cellular activities through graphs. Cell directionality was calculated as the cosine value of the angle formed by the EF vector and cell migration. To further demonstrate the impact of EFs on the pulmonary tissue, the human bronchial epithelial cells transformed with Ad12-SV40 2B (BEAS-2B cells) were obtained and experimented under the same conditions as AECs. To determine the influence on cell fate, cells underwent electric stimulation were collected to perform Western blot analysis.@*RESULTS@#The successful separation and culturing of AECs were confirmed through immunofluorescence staining. Compared with the control, AECs in EFs demonstrated a significant directionality in a voltage-dependent way. In general, type Ⅰ alveolar epithelial cells migrated faster than type Ⅱ alveolar epithelial cells, and under EFs, these two types of cells exhibited different response threshold. For type Ⅱ alveolar epithelial cells, only EFs at 200 mV/mm resulted a significant difference to the velocity, whereas for, EFs at both 100 mV/mm and 200 mV/mm gave rise to a significant difference. Western blotting suggested that EFs led to an increased expression of a AKT and myeloid leukemia 1 and a decreased expression of Bcl-2-associated X protein and Bcl-2-like protein 11.@*CONCLUSION@#EFs could guide and accelerate the directional migration of AECs and exert antiapoptotic effects, which indicated that EFs are important biophysical signals in the re-epithelialization of alveolar epithelium in lung injury.


Assuntos
Humanos , Ratos , Animais , Células Epiteliais Alveolares , Pulmão , Lesão Pulmonar , Movimento Celular/fisiologia
19.
J Am Chem Soc ; 144(45): 20895-20902, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36345048

RESUMO

Electrochemical conversion of propene is a promising technique for manufacturing commodity chemicals by using renewable electricity. To achieve this goal, we still need to develop high-performance electrocatalysts for propene electrooxidation, which highly relies on understanding the reaction mechanism at the molecular level. Although the propene oxidation mechanism has been well investigated at the solid/gas interface under thermocatalytic conditions, it still remains elusive at the solid/liquid interface under an electrochemical environment. Here, we report the mechanistic studies of propene electrooxidation on PdO/C and Pd/C catalysts, considering that the Pd-based catalyst is one of the most promising electrocatalytic systems. By electrochemical in situ attenuated total reflection Fourier transform infrared spectroscopy, a distinct reaction pathway was observed compared with conventional thermocatalysis, emphasizing that propene can be dehydrogenated at a potential higher than 0.80 V, and strongly adsorb via µ-C═CHCH3 and µ3-η2-C═CHCH3 configuration on PdO and Pd, respectively. The µ-C═CHCH3 is via bridge bonds on adjacent Pd and O atoms on PdO, and it can be further oxidized by directly taking surface oxygen from PdO, verified by the H218O isotope-edited experiment. A high surface oxygen content on PdO/C results in a 3 times higher turnover frequency than that on Pd/C for converting propene into propene glycol. This finding highlights the different reaction pathways under an electrochemical environment, which sheds light on designing next-generation electrocatalysts for propene electrooxidation.

20.
Nat Commun ; 13(1): 7071, 2022 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-36400778

RESUMO

Anti-CRISPRs (Acrs) are natural inhibitors of bacteria's CRISPR-Cas systems, and have been developed as a safeguard to reduce the off-target effects of CRISPR gene-editing technology. Acrs can directly bind to CRISPR-Cas complexes and inhibit their activities. However, whether this process is under regulation in diverse eukaryotic cellular environments is poorly understood. In this work, we report the discovery of a redox switch for NmeAcrIIC1, which regulates NmeAcrIIC1's monomer-dimer interconversion and inhibitory activity on Cas9. Further structural studies reveal that a pair of conserved cysteines mediates the formation of inactive NmeAcrIIC1 dimer and directs the redox cycle. The redox switch also applies to the other two AcrIIC1 orthologs. Moreover, by replacing the redox-sensitive cysteines, we generated a robust AcrIIC1 variant that maintains potent inhibitory activity under various redox conditions. Our results reveal a redox-dependent regulation mechanism of Acr, and shed light on the design of superior Acr for CRISPR-Cas systems.


Assuntos
Proteína 9 Associada à CRISPR , Edição de Genes , Proteína 9 Associada à CRISPR/metabolismo , Edição de Genes/métodos , Sistemas CRISPR-Cas , Oxirredução
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