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1.
Sci Total Environ ; 927: 172064, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38569968

RESUMO

Soil parent material is the second most influential factor in pedogenesis, influencing soil properties and microbial communities. Different assembly processes shape diverse functional microbial communities. The question remains unresolved regarding how these ecological assembly processes affect microbial communities and soil functionality within soils on different parent materials. We collected soil samples developed from typical parent materials, including basalt, granite, metamorphic rock, and marine sediments across soil profiles at depths of 0-20, 20-40, 40-80, and 80-100 cm, within rubber plantations on Hainan Island, China. We determined bacterial community characteristics, community assembly processes, and soil enzyme-related functions using 16S rRNA high-throughput sequencing and enzyme activity analyses. We found homogeneous selection, dispersal limitation, and drift processes were the dominant drivers of bacterial community assembly across soils on different parent materials. In soils on basalt, lower pH and higher moisture triggered a homogeneous selection-dominated assembly process, leading to a less diverse community but otherwise higher carbon and nitrogen cycling enzyme activities. As deterministic process decreased, bacterial community diversity increased with stochastic process. In soils on marine sediments, lower water, carbon, and nutrient content limited the dispersal of bacterial communities, resulting in higher community diversity and an increased capacity to utilize relative recalcitrant substrates by releasing more oxidases. The r-strategy Bacteroidetes and genera Sphingomonas, Bacillus, Vibrionimonas, Ochrobactrum positively correlated with enzyme-related function, whereas k-strategy Acidobacteria, Verrucomicrobia and genera Acidothermus, Burkholderia-Caballeronia-Paraburkholderia, HSB OF53-F07 showed negative correlations. Our study suggests that parent material could influence bacterial community assembly processes, diversity, and soil enzyme-related functions via soil properties.


Assuntos
Bactérias , Microbiota , Microbiologia do Solo , Solo , Solo/química , China , RNA Ribossômico 16S , Biodiversidade
2.
J Ethnopharmacol ; 330: 118224, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38642623

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sophorae tonkinensis Radix et Rhizoma (STR) is an extensively applied traditional Chinese medicine (TCM) in southwest China. However, its clinical application is relatively limited due to its hepatotoxicity effects. AIM OF THE STUDY: To understand the material foundation and liver injury mechanism of STR. MATERIALS AND METHODS: Chemical compositions in STR and its prototypes in mice were profiled by ultra-performance liquid chromatography coupled quadrupole-time of flight mass spectrometry (UPLC-Q/TOF MS). STR-induced liver injury (SILI) was comprehensively evaluated by STR-treated mice mode. The histopathologic and biochemical analyses were performed to evaluate liver injury levels. Subsequently, network pharmacology and multi-omics were used to analyze the potential mechanism of SILI in vivo. And the target genes were further verified by Western blot. RESULTS: A total of 152 compounds were identified or tentatively characterized in STR, including 29 alkaloids, 21 organic acids, 75 flavonoids, 1 quinone, and 26 other types. Among them, 19 components were presented in STR-medicated serum. The histopathologic and biochemical analysis revealed that hepatic injury occurred after 4 weeks of intragastric administration of STR. Network pharmacology analysis revealed that IL6, TNF, STAT3, etc. were the main core targets, and the bile secretion might play a key role in SILI. The metabolic pathways such as taurine and hypotaurine metabolism, purine metabolism, and vitamin B6 metabolism were identified in the STR exposed groups. Among them, taurine, hypotaurine, hypoxanthine, pyridoxal, and 4-pyridoxate were selected based on their high impact value and potential biological function in the process of liver injury post STR treatment. CONCLUSIONS: The mechanism and material foundation of SILI were revealed and profiled by a multi-omics strategy combined with network pharmacology and chemical profiling. Meanwhile, new insights were taken into understand the pathological mechanism of SILI.

3.
Skin Res Technol ; 30(4): e13713, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38634160

RESUMO

OBJECTIVE: Alopecia areata (AA) is often characterized by sudden onset of patchy hair loss. Topical corticosteroid injection is the most common treatment. This study retrospectively observed the clinical efficacy of microneedle minoxidil combined with triamcinolone acetonide in the treatment of AA. METHODS: A total of 230 patients with AA were selected. The experimental group (n = 120) received physician training and home microneedle treatment with minoxidil combined with triamcinolone acetonide once a week. Topical minoxidil and triamcinolone acetonide were used twice daily at other times. The control group (n = 110) was treated with minoxidil combined with triamcinolone acetonide, twice a day. Cure rate, response rate, SALT, dermatological Quality of Life Index (DLQI), visual analogue (VAS), and cost were assessed at weeks 4 and 12. RESULTS: Treated group SALT score(Severity of Alopecia Tool) remarkable lower than control group after treated 4 and 12 weeks. After 12 weeks treatment, DLQI score of the treated group (1.8 ± 1.67) were significantly lower than those of the control group (2.45 ± 1.88) (p < 0.05). VAS score and adverse reaction between two group showed no significant different (p = 0.823, p = 0.484 respectively). The total cost was 53.93 ± 15.85 in the treatment group and 53.26 ± 11.51 in the control group. There was no significant difference between the two groups (p = 0.72). In the treated group, the complete response rate (CR: 78.33%) and total effective rate (CR+PR: 95%) were significantly higher than those in the control group (CR: 40.91% and CR+PR: 51.82%), with statistically significant differences (p < 0.001). CONCLUSION: Microneedle introduction of minoxidil and triamcinolone acetonide in the treatment of AA is a safe, effective, economical, and convenient method, with few adverse reactions, and has a good application prospect.


Assuntos
Alopecia em Áreas , Humanos , Alopecia em Áreas/tratamento farmacológico , Triancinolona Acetonida/uso terapêutico , Minoxidil/uso terapêutico , Estudos Retrospectivos , Qualidade de Vida , Alopecia/tratamento farmacológico , Resultado do Tratamento
4.
Phytochemistry ; 222: 114096, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38641141

RESUMO

Forsythiae Fructus (FF), the dried fruit of F. suspensa, is commonly used to treat fever, inflammation, etc in China or other Asian countries. FF is usually used as the core herb in traditional Chinese medicine preparations for the treatment of influenza, such as Shuang-huang-lian oral liquid and Yin-qiao powder, etc. Since the wide application and core role of FF, its research progress was summarized in terms of traditional uses, phytochemistry, pharmacology, pharmacokinetics, quality control, and toxicity. Meanwhile, the anti-influenza substances and mechanism of FF were emphasized. Till now, a total of 290 chemical components are identified in F. suspensa, and among them, 248 components were isolated and identified from FF, including 42 phenylethanoid glycosides, 48 lignans, 59 terpenoids, 14 flavonoids, 3 steroids, 24 cyclohexyl ethanol derivatives, 14 alkaloids, 26 organic acids, and 18 other types. FF and their pure compounds have the pharmacological activities of anti-virus, anti-inflammation, anti-oxidant, anti-bacteria, anti-tumor, neuroprotection, hepatoprotection, etc. Inhibition of TLR7, RIG-I, MAVS, NF-κB, MyD88 signaling pathway were the reported anti-influenza mechanisms of FF and phenylethanoid glycosides and lignans are the main active groups. However, the bioavailability of phenylethanoid glycosides and lignans of FF in vivo was low, which needed to be improved. Simultaneously, the un-elucidated compounds and anti-influenza substances of FF strongly needed to be explored. The current quality control of FF was only about forsythoside A and phillyrin, more active components should be taken into consideration. Moreover, there are no reports of toxicity of FF yet, but the toxicity of FF should be not neglected in clinical applications.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38662561

RESUMO

In a clinical setting, the acquisition of certain medical image modality is often unavailable due to various considerations such as cost, radiation, etc. Therefore, unpaired cross-modality translation techniques, which involve training on the unpaired data and synthesizing the target modality with the guidance of the acquired source modality, are of great interest. Previous methods for synthesizing target medical images are to establish one-shot mapping through generative adversarial networks (GANs). As promising alternatives to GANs, diffusion models have recently received wide interests in generative tasks. In this paper, we propose a target-guided diffusion model (TGDM) for unpaired cross-modality medical image translation. For training, to encourage our diffusion model to learn more visual concepts, we adopted a perception prioritized weight scheme (P2W) to the training objectives. For sampling, a pre-trained classifier is adopted in the reverse process to relieve modality-specific remnants from source data. Experiments on both brain MRI-CT and prostate MRI-US datasets demonstrate that the proposed method achieves a visually realistic result that mimics a vivid anatomical section of the target organ. In addition, we have also conducted a subjective assessment based on the synthesized samples to further validate the clinical value of TGDM.

6.
Angew Chem Int Ed Engl ; : e202405379, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38639181

RESUMO

Due to the superior catalytic activity and efficient utilization of noble metals, nanocatalysts are extensively used in the modern industrial production of chemicals. The surface structures of these materials are significantly influenced by reactive adsorbates, leading to dynamic behavior under experimental conditions. The dynamic nature poses significant challenges in studying the  structure-activity relations of catalysts. Herein, we unveil an anomalous entropic effect on catalysis via surface pre-melting of nanoclusters through machine learning accelerated molecular dynamics and free energy calculation. We find that due to the pre-melting of shell atoms, there exists a non-linear variation in the catalytic activity of the nanoclusters with temperature. Consequently, two notable changes in catalyst activity occur at the respective temperatures of melting for the shell and core atoms. We further study the nanoclusters with surface point defects, i.e. vacancy and ad-atom, and observe significant decrease in the surface melting temperatures of the nanoclusters, enabling the reaction to take place under more favorable and milder conditions. These findings not only provide novel insights into dynamic catalysis of nanoclusters  but also offer new understanding of the role of point defects in catalytic processes.

7.
J Med Virol ; 96(4): e29510, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38573018

RESUMO

Hepatitis B virus (HBV) infection poses a significant burden on global public health. Unfortunately, current treatments cannot fully alleviate this burden as they have limited effect on the transcriptional activity of the tenacious covalently closed circular DNA (cccDNA) responsible for viral persistence. Consequently, the HBV life cycle should be further investigated to develop new anti-HBV pharmaceutical targets. Our previous study discovered that the host gene TMEM203 hinders HBV replication by participating in calcium ion regulation. The involvement of intracellular calcium in HBV replication has also been confirmed. In this study, we found that transient receptor potential vanilloid 4 (TRPV4) notably enhances HBV reproduction by investigating the effects of several calcium ion-related molecules on HBV replication. The in-depth study showed that TRPV4 promotes hepatitis B core/capsid protein (HBc) protein stability through the ubiquitination pathway and then promotes the nucleocapsid assembly. HBc binds to cccDNA and reduces the nucleosome spacing of the cccDNA-histones complex, which may regulate HBV transcription by altering the nucleosome arrangement of the HBV genome. Moreover, our results showed that TRPV4 promotes cccDNA-dependent transcription by accelerating the methylation modification of H3K4. In conclusion, TRPV4 could interact with HBV core protein and regulate HBV during transcription and replication. These data suggest that TRPV4 exerts multifaceted HBV-related synergistic factors and may serve as a therapeutic target for CHB.


Assuntos
Antineoplásicos , Hepatite B , Humanos , Ubiquitina , Capsídeo , Proteínas do Capsídeo , Vírus da Hepatite B/genética , Canais de Cátion TRPV/genética , Cálcio , Nucleossomos , Metilação , Proteínas de Membrana
8.
J Am Chem Soc ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38659097

RESUMO

Due to the increased concern about energy and environmental issues, significant attention has been paid to the development of large-scale energy storage devices to facilitate the utilization of clean energy sources. The redox flow battery (RFB) is one of the most promising systems. Recently, the high cost of transition-metal complex-based RFB has promoted the development of aqueous RFBs with redox-active organic molecules. To expand the working voltage, computational chemistry has been applied to search for organic molecules with lower or higher redox potentials. However, redox potential computation based on implicit solvation models would be challenging due to difficulty in parametrization when considering the complex solvation of supporting electrolytes. Besides, although ab initio molecular dynamics (AIMD) describes the supporting electrolytes with the same level of electronic structure theory as the redox couple, the application is impeded by the high computation costs. Recently, machine learning molecular dynamics (MLMD) has been illustrated to accelerate AIMD by several orders of magnitude without sacrificing the accuracy. It has been established that redox potentials can be computed by MLMD with two separated machine learning potentials (MLPs) for reactant and product states, which is redundant and inefficient. In this work, an automated workflow is developed to construct a universal MLP for both states, which can compute the redox potentials or acidity constants of redox-active organic molecules more efficiently. Furthermore, the predicted redox potentials can be evaluated at the hybrid functional level with much lower costs, which would facilitate the design of aqueous organic RFBs.

9.
Plant Mol Biol ; 114(3): 46, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630415

RESUMO

Peach fruit rapidly soften after harvest, a significant challenge for producers and marketers as it results in rotting fruit and significantly reduces shelf life. In this study, we identified two tandem genes, PpNAC1 and PpNAC5, within the sr (slow ripening) locus. Phylogenetic analysis showed that NAC1 and NAC5 are highly conserved in dicots and that PpNAC1 is the orthologous gene of Non-ripening (NOR) in tomato. PpNAC1 and PpNAC5 were highly expressed in peach fruit, with their transcript levels up-regulated at the onset of ripening. Yeast two-hybrid and bimolecular fluorescence complementation assays showed PpNAC1 interacting with PpNAC5 and this interaction occurs with the tomato and apple orthologues. Transient gene silencing experiments showed that PpNAC1 and PpNAC5 positively regulate peach fruit softening. Yeast one-hybrid and dual luciferase assays and LUC bioluminescence imaging proved that PpNAC1 and PpNAC5 directly bind to the PpPGF promoter and activate its transcription. Co-expression of PpNAC1 and PpNAC5 showed higher levels of PpPGF activation than expression of PpNAC1 or PpNAC5 alone. In summary, our findings demonstrate that the tandem transcription factors PpNAC1 and PpNAC5 synergistically activate the transcription of PpPGF to regulate fruit softening during peach fruit ripening.


Assuntos
Prunus persica , Solanum lycopersicum , Prunus persica/genética , Frutas/genética , Filogenia , Saccharomyces cerevisiae , Solanum lycopersicum/genética , Fatores de Transcrição/genética
10.
Front Immunol ; 15: 1362970, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38629071

RESUMO

Background: T cell exhaustion in the tumor microenvironment has been demonstrated as a substantial contributor to tumor immunosuppression and progression. However, the correlation between T cell exhaustion and osteosarcoma (OS) remains unclear. Methods: In our present study, single-cell RNA-seq data for OS from the GEO database was analysed to identify CD8+ T cells and discern CD8+ T cell subsets objectively. Subgroup differentiation trajectory was then used to pinpoint genes altered in response to T cell exhaustion. Subsequently, six machine learning algorithms were applied to develop a prognostic model linked with T cell exhaustion. This model was subsequently validated in the TARGETs and Meta cohorts. Finally, we examined disparities in immune cell infiltration, immune checkpoints, immune-related pathways, and the efficacy of immunotherapy between high and low TEX score groups. Results: The findings unveiled differential exhaustion in CD8+ T cells within the OS microenvironment. Three genes related to T cell exhaustion (RAD23A, SAC3D1, PSIP1) were identified and employed to formulate a T cell exhaustion model. This model exhibited robust predictive capabilities for OS prognosis, with patients in the low TEX score group demonstrating a more favorable prognosis, increased immune cell infiltration, and heightened responsiveness to treatment compared to those in the high TEX score group. Conclusion: In summary, our research elucidates the role of T cell exhaustion in the immunotherapy and progression of OS, the prognostic model constructed based on T cell exhaustion-related genes holds promise as a potential method for prognostication in the management and treatment of OS patients.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Análise da Expressão Gênica de Célula Única , Exaustão das Células T , Osteossarcoma/genética , Neoplasias Ósseas/genética , Imunidade , Microambiente Tumoral/genética , Proteínas de Ligação a DNA , Enzimas Reparadoras do DNA
11.
bioRxiv ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38585878

RESUMO

Antisense therapeutics such as splice-modulating antisense oligonucleotides (ASOs) are promising tools to treat diseases caused by splice-altering intronic variants. However, their testing in animal models is hampered by the generally poor sequence conservation of the intervening sequences between human and other species. Here we aimed to model in the mouse a recurrent, deep-intronic, splice-activating, COL6A1 variant, associated with a severe form of Collagen VI-related muscular dystrophies (COL6-RDs), for the purpose of testing human-ready antisense therapeutics in vivo. The variant, c.930+189C>T, creates a donor splice site and inserts a 72-nt-long pseudoexon, which, when translated, acts in a dominant-negative manner, but which can be skipped with ASOs. We created a unique humanized mouse allele (designated as "h"), in which a 1.9 kb of the mouse genomic region encoding the amino-terminus (N-) of the triple helical (TH) domain of collagen a1(VI) was swapped for the human orthologous sequence. In addition, we also created an allele that carries the c.930+189C>T variant on the same humanized knock-in sequence (designated as "h+189T"). We show that in both models, the human exons are spliced seamlessly with the mouse exons to generate a chimeric mouse-human collagen a1(VI) protein. In homozygous Col6a1 h+189T/h+189T mice, the pseudoexon is expressed at levels comparable to those observed in heterozygous patients' muscle biopsies. While Col6a1h/h mice do not show any phenotype compared to wildtype animals, Col6a1 h/h+189T and Col6a1 h+189T/h+189T mice have smaller muscle masses and display grip strength deficits detectable as early as 4 weeks of age. The pathogenic h+189T humanized knock-in mouse allele thus recapitulates the pathogenic splicing defects seen in patients' biopsies and allows testing of human-ready precision antisense therapeutics aimed at skipping the pseudoexon. Given that the COL6A1 N-TH region is a hot-spot for COL6-RD variants, the humanized knock-in mouse model can be utilized as a template to introduce other COL6A1 pathogenic variants. This unique humanized mouse model thus represents a valuable tool for the development of antisense therapeutics for COL6-RDs.

12.
Medicine (Baltimore) ; 103(14): e37706, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579031

RESUMO

RATIONALE: Kaposiform hemangioendothelioma is an aggressive vascular tumor that is often associated with life-threatening coagulopathies and Kasabach-Merritt phenomenon. Pathologic biopsies can provide a good basis for diagnosis and treatment. Therapy with srolimus combined with glucocorticoids may offer patients a favorable prognosis. PATIENT CONCERNS: A large purplish-red mass on the knee of a child with extremely progressive thrombocytopenia and refractory coagulation abnormalities. Conventional doses of glucocorticoids alone failed to improve coagulation abnormalities and the child developed large cutaneous petechiae and scalp hematomas. DIAGNOSIS: Kaposiform hemangioendothelioma combined with Kasabach-Merritt phenomenon. INTERVENTIONS: The patient received prednisolone 2.0 mg/kg*d for 4 days. Blood products were transfused to ensure vital signs and to complete the pathologic biopsy. Sirolimus combined with prednisolone was given after clarifying the diagnosis of Kaposiform hemangioendothelioma. OUTCOMES: The tumor basically disappeared on examination and the ultrasound showed a subcutaneous hyperechoic mass with normal blood flow. LESSONS: Sirolimus combined with glucocorticoids is effective in controlling Kasabach-Merritt phenomenon and pathologic biopsy is important for definitive diagnosis.


Assuntos
Transtornos da Coagulação Sanguínea , Hemangioendotelioma , Síndrome de Kasabach-Merritt , Sarcoma de Kaposi , Humanos , Recém-Nascido , Transtornos da Coagulação Sanguínea/complicações , Glucocorticoides/uso terapêutico , Hemangioendotelioma/complicações , Hemangioendotelioma/tratamento farmacológico , Hemangioendotelioma/diagnóstico , Síndrome de Kasabach-Merritt/tratamento farmacológico , Prednisolona/uso terapêutico , Sarcoma de Kaposi/patologia , Sirolimo/uso terapêutico
13.
Int J Biol Macromol ; 267(Pt 1): 131435, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38593900

RESUMO

This study represents the inaugural investigation into the effect of cold plasma (CP) pretreatment combined with sodium periodate on the preparation of dialdehyde starch (DAS) from native maize starch and its consequent effects on the properties of DAS. The findings indicate that the maize starch underwent etching by the plasma, leading to an increase in the particle size of the starch, which in turn weakened the rigid structure of the starch and reduced its crystallinity. Concurrently, the plasma treatment induced cleavage of the starch molecular chain, resulting in a decrease in the viscosity of the starch and an enhancement of its fluidity. These alterations facilitated an increased contact area between the starch and the oxidising agent sodium periodate, thereby augmenting the efficiency of the DAS preparation reaction. Consequently, the aldehyde group content was elevated by 9.98 % compared to the conventional DAS preparation methodology. Therefore, CP could be an efficient and environmentally friendly non-thermal processing method to assist starch oxidation for DAS preparation and property enhancement.

14.
Nat Commun ; 15(1): 3201, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615046

RESUMO

Yttrium iron garnet, a material possessing ultralow magnetic damping and extraordinarily long magnon diffusion length, is the most widely studied magnetic insulator in spintronics and magnonics. Field-free electrical control of perpendicular yttrium iron garnet magnetization with considerable efficiency is highly desired for excellent device performance. Here, we demonstrate such an accomplishment with a collinear spin current, whose spin polarization and propagation direction are both perpendicular to the interface. Remarkably, the field-free magnetization switching is achieved not only with a heavy-metal-free material, Permalloy, but also with a higher efficiency as compared with a typical heavy metal, Pt. Combined with the direct and inverse effect measurements, we ascribe the collinear spin current to the anomalous spin Hall effect in Permalloy. Our findings provide a new insight into spin current generation in Permalloy and open an avenue in spintronic devices.

15.
Transl Lung Cancer Res ; 13(3): 573-586, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38601448

RESUMO

Background: The ability to predict survival in patients with lymph node metastasis has long been elusive. After surgery, the basis for decision-making on the combination treatment of patients is not clear. The purpose of this study was thus to build a survival nomogram model to effectively predict the overall survival (OS) of patients with non-small cell lung cancer (NSCLC) and lymph node metastasis. The number of dissected lymph nodes (NDLN), number of positive lymph nodes (NPLN), lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) were included in this study to determine the risk factors in patients with advanced NSCLC. Methods: The data of 5,132 patients with NSCLC and lymph node metastasis (N1 or N2) were extracted from the Surveillance, Epidemiology, and End Results (SEER) database according to inclusion and exclusion criteria and used as the training cohort. We enrolled 117 patients from the First Affiliated Hospital, Zhejiang University School of Medicine as the external validation cohort. Receiver operating characteristic (ROC) analyses were performed to determine the best cutoff values for predicting the prognosis of patients with NSCLC. Based on the risk factors affecting prognosis, a nomogram was constructed using univariate and multivariate Cox proportional hazard regression models. The discrimination ability of the nomogram was evaluated with the concordance index (C-index) and calibration curves. For the independent risk factors, survival curves were drawn using Kaplan-Meier analysis. Results: ROC curve analysis showed that the optimal NPLN cut-off value was 4, LNR was 0.26, and LODDS was -0.25, respectively. However, LNR was nonsignificant in multivariate analysis, with a P value of 0.274. The novel survival nomogram model included seven independent risk factors, among which were NPLN, LODDS, and chemotherapy. Model 4, which included N stage, NPLN, and LODDS, had a higher likelihood ratio (LR) and C-index than did the other models. The C-index was 0.648 [95% confidence interval (CI): 0.636-0.659] in the training cohort and 0.807 (95% CI: 0.751-0.863) in the external validation cohort, showing good prognostic accuracy and discrimination ability. According to the median risk score, the patients in the training cohort and external validation cohort were divided into high-risk and low-risk groups, between which significant differences in OS were found. In the training cohort, age, sex, T stage, N stage, NPLN, LODDS, and chemotherapy were significantly associated with OS (P<0.001). In the external validation cohort, T stage, NPLN, LODDS, and chemotherapy were found to be correlated with OS. Conclusions: The NPLN and LODDS nomogram is an accurate survival prediction tool for patients with N1 or N2 NSCLC. Patients with lymph node metastasis can benefit from chemotherapy, but no evidence shows that radiotherapy is necessary for patients with resectable NSCLC.

16.
Sci Rep ; 14(1): 8161, 2024 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589540

RESUMO

Tenofovir disoproxil fumarate (TDF) seems to prevent hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV). However, the mechanism is still little known. This study aimed to investigate the the roles and mechanisms of TDF, tenofovir alafenamide fumarate (TAF), and entecavir (ETV) on the malignant characteristics of liver cancer cells. Using the wound-healing assays, transwell assays, matrigel transwell assays, and cell counting kit-8 (CCK-8) assays, it was possible to identify that TDF/TAF, inhibited migration, invasion, and proliferation of HepG2 cells and Huh7 cells. To investigate the mechanisms, we performed TOP/FOP-Flash system, Western blot, and RT-qPCR assays of liver cancer cells cultured with TDF/TAF and found a lower activity of Wnt/ß-catenin signaling pathway compared with control cells. Finally, Hepatitis C virus p7 trans-regulated protein 3 (p7TP3), a tumor suppressor in liver cancers, was significantly increased in HepG2 cells and Huh7 cells that treated with TDF/TAF. However, entecavir (ETV)-treated liver cancer cells showed no significant difference in the malignant characteristics of liver cancer cells, activity of Wnt/ß-catenin signaling pathway, and expression of p7TP3, compared with the control groups. To conclude, TDF/TAF maybe novel promising therapeutic strategy for liver cancers, including HCC and hepatoblastoma, via Wnt/ß-catenin signaling pathway, by up-regulating expression of the tumor suppressor, p7TP3.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Tenofovir/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Alanina/uso terapêutico , Adenina/uso terapêutico , Processos Neoplásicos , Movimento Celular , Antivirais/uso terapêutico
17.
Foods ; 13(7)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38611437

RESUMO

The postharvest softening and corresponding quality deterioration of blueberry fruits are crucial factors that hinder long-distance sales and long-term storage. Cold plasma (CP) is an effective technology to solve this, but the specific mechanism of delaying fruit softening remains to be revealed. Here, this study found that CP significantly improved blueberry hardness. Physiological analysis showed that CP regulated the dynamic balance of reactive oxygen species (ROS) to maintain hardness by increasing antioxidant content and antioxidant enzyme activity, resulting in a 12.1% decrease in the H2O2 content. Transcriptome analysis revealed that CP inhibited the expression of cell wall degradation-related genes such as the pectin hydrolase gene and cellulase gene, but up-regulated the genes of the ROS-scavenging system. In addition, the resistance genes in the MAPK signaling pathway were also activated by CP in response to fruit ripening and softening and exhibited positive response characteristics. These results indicate that CP can effectively regulate the physiological characteristics of blueberries at a genetic level and delay the softening process, which is of great significance to the storage of blueberries.

18.
Int J Biol Macromol ; 267(Pt 2): 131578, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38641267

RESUMO

The impact of Dielectric-Barrier Discharge (DBD) plasma treatment on the prevention of heat-induced aggregation of Ovalbumin (OVA) and improvement in emulsification properties was investigated. Results highlighted the effective inhibition of thermal aggregation of OVA following exposure to plasma. Structural analysis revealed that the plasma-induced oxidation of sulfhydryl and intermolecular disulfide bonds played a pivotal role in inhibiting the thermal aggregation, considered by Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE), multiplies spectroscopy, and analysis of dynamic exchange of sulfhydryl-disulfide bonds. Meanwhile, the oxidation of exposed hydrophobic sites due to plasma treatment resulted in the transformation of the OVA molecule's surface from hydrophobic to hydrophilic, contributing significantly to the aggregation inhibition. Additionally, compared to an untreated sample of OVA, almost one-fold increase in emulsifying ability (EAI) and 1.5-fold in emulsifying stability (ESI) was observed after 4 min of plasma treatment. These findings demonstrated that plasma treatment not only enhanced the thermal stability of OVA, but also improved its emulsification properties.

19.
IEEE Trans Cybern ; PP2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38451753

RESUMO

This work involves the sliding mode control (SMC) issue for a class of Markov jump singularly perturbed systems (MJSPSs) under consideration of unmatched external disturbances and communication constraints. For the first time, the piecewise homogeneous Markov chain (MC) which depends on the system mode and the controller mode is applied to control the scheduling of stochastic communication protocol (SCP), so that the MCs in the system models, the controller and the SCP constitute a three-layer nonstationary Markov model (NMM). This model perfectly describes the different objects of the three MCs and reflects the mutual regulation among them. The critical issue is to devise an adaptive controller and a sliding surface (SS) simultaneously under SCP scheduling. By applying a standard singular sliding mode surface, an appropriate nonstationary SMC law is established to promise the accessibility of the SS and the stability of the closed-loop system (CLS), and meet the expected performance indicator. Further, using the mode-dependent Lyapunov function and piecewise homogeneous Markov model method, sufficient criteria are obtained. The specific expression of the control gain is obtained by matrix decoupling technology. Finally, a numerical simulation is furnished to testify the correctness of the conclusion.

20.
J Pain Res ; 17: 817-825, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444878

RESUMO

Introduction: Acupuncture is effective for patients with chronic low back pain (CLBP), which can relieve pain intensity and regulate negative emotional states such as pain-related anxiety and depression. Previous studies mainly discuss the analgesic mechanism of acupuncture treatment of CLBP, but there are multiple dimensions to pain, including sensation, emotion and cognition. Therefore, this study aims to investigate the central mechanism of acupuncture for CLBP from the perspective of emotional regulation by functional magnetic resonance imaging (fMRI). Methods and Analysis: A total of 72 patients with CLBP will be recruited in the study and randomly assigned to the verum acupuncture group or the sham acupuncture group. The trail will last for 18 weeks including a 2-week baseline, a 4-week treatment and a 12-week for follow-up period. The primary outcomes are the visual analog scale (VAS) and the Japanese Orthopaedic Association Scores (JOA) score. The secondary outcomes are the 12-item short form health survey (SF-12), the state trait anxiety inventory (STAI), the self-rating anxiety scale (SAS) and self-rating depression scale (SDS). The VAS, JOA, STAI SAS and SDS will be collected at baseline, week 2, week 4, and after follow-up. The SF-12 will be evaluated at baseline, week 2 and week 4. Functional magnetic resonance imaging (MRI) data will be collected at baseline and the end of treatment. Emotion-related brain regions will be chosen as regions of interest (ROIs). The gray matter volume (GMV), amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), functional connectivity (FC), and large-scale functional brain network based on these ROIs will be analyzed within and between the two groups. Discussion: This study will verify the emotional regulation of acupuncture and explore the mechanism of acupuncture for emotion regulation in patients with CLBP. Trial Registration Number: https://www.chictr.org.cn/showproj.html?proj=195486, identifier: ChiCTR2300070557.

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