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1.
Front Endocrinol (Lausanne) ; 15: 1347762, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38567311

RESUMO

Objective: Hormone receptor (HR)-low/HER2-negative breast cancers (BCs) are more likely to be basal-like BCs, with similar molecular features and gene expression profiles to HR-negative (estrogen receptor <1% or negative and progesterone receptor <1% or negative) BCs. Recently, with the clinical application of adjuvant intensive therapy for triple-negative breast cancer (TNBC), the prognosis of TNBC patients without pathological complete response (pCR) has significantly improved. Therefore, it is necessary to reanalyse the prognostic characteristics of clinically high-risk HR-low/HER2-negative BC. Methods: According to the inclusion and exclusion standards, 288 patients with HR-low/HER2-negative BC and TNBC who received NAC and were followed up between 2015 and 2022 at three breast centres in Hunan Province, China, were enrolled. Inverse probability of treatment weighting (IPTW) was utilized to mitigate imbalances in baseline characteristics between the HR-low/HER2-negative BC group and TNBC group regarding event-free survival (EFS) and overall survival (OS). The primary clinical endpoints were pCR and EFS, while the secondary endpoints included OS, objective response rate (ORR), and clinical benefit rate (CBR). Results: The pCR rate (27.1% vs. 28.0%, P = 1.000), ORR rate (76.9% vs. 78.3%, P = 0.827) and CBR rate (89.7% vs. 96.5%, P = 0.113) after NAC were similar between the HR-low/HER2-negative BC and the TNBC group. EFS in patients with non-pCR from the 2 groups was significantly inferior in comparison to patients with pCR (P = 0.001), and the 3-year EFS was 94.74% (95% CI = 85.21% to 100.00%) and 57.39% (95% CI =43.81% to 75.19%) in patients with pCR and non-pCR from the HR-low/HER2-negative BC group, respectively, and 89.70% (95% CI = 82.20% to 97.90%) and 69.73% (95% CI = 62.51% to 77.77%) in the TNBC patients with pCR and non-pCR, respectively. Conclusions: In the real world, the therapeutic effects of NAC for HR-low/HER2-negative BCs and TNBCs were similar. EFS of patients with non-pCR in the HR-low/HER2-negative BC group was inferior to that of the TNBC group with non-pCR, suggesting that it is necessary to explore new adjuvant intensive therapy strategies for these patients.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Terapia Neoadjuvante , Prognóstico , Estudos de Coortes , China
2.
Support Care Cancer ; 32(5): 284, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607445

RESUMO

OBJECTIVE: This longitudinal study aims to examine the present state of perceived control, self-management efficacy, and overall quality of life (QoL) in patients with breast cancer undergoing radiotherapy, and gain insight into the dynamic trends and factors that influence the quality of life experienced by patients during the course of radiotherapy. METHODS: Participants completed the Cancer Experience and Efficacy Scale (CEES), Strategies Used by People to Promote Health (SUPPH), and Functional Assessment of Cancer Therapy- Breast (FACT-B). The data was analyzed using the software SPSS26.0. Repeated measures analysis of variance (ANOVA) and mixed-effects linear models were used to analyze trends in perceived control, self-management efficacy, and QoL at three-time points, as well as factors affecting QoL during radiotherapy. RESULTS: Perceived control and self-management efficacy were associated with QoL over the course of the radiotherapy. Self-management efficacy (ß = 0.30, P < 0.001), presence of chemotherapy (ß = 18.33, P = 0.024), and duration of illness (ß = 2.25, P = 0.028) had a positive effect on the change in QoL, while time (ß = - 2.95, P < 0.001), cancer experience (ß = - 0.46, P < 0.001), and type of medical insurance (ß = - 2.77, P = 0.021) had the negative effect on the change in QoL. CONCLUSION: The QoL, perceived control, and self-efficacy of patients with breast cancer show dynamic changes during radiotherapy. The higher the self-efficacy, the better the QoL, and the worse the QoL when the sense of disease control is poor. At the same time, more attention should be paid to the QoL of breast cancer radiotherapy patients with a long course of the disease, receiving chemotherapy, and different medical payment methods.


Assuntos
Neoplasias da Mama , Autogestão , Humanos , Feminino , Neoplasias da Mama/radioterapia , Qualidade de Vida , Estudos Longitudinais , Promoção da Saúde , Autoeficácia
3.
World J Gastrointest Oncol ; 16(2): 493-513, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38425392

RESUMO

BACKGROUND: Gastric cancer (GC) is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis. Resveratrol, a non-flavonoid polyphenolic compound found in a variety of Chinese medicinal materials, has shown excellent anti-GC effect. However, its exact mechanisms of action in GC have not been clarified. AIM: To identify the effects of resveratrol on GC progression and explore the related molecular mechanisms. METHODS: Action targets of resveratrol and GC-related targets were screened from public databases. The overlapping targets between the two were confirmed using a Venn diagram, and a "Resveratrol-Target-GC" network was constructed using Cytoscape software version 3.9.1. The protein-protein interaction (PPI) network was constructed using STRING database and core targets were identified by PPI network analysis. The Database for Annotation, Visualization and Integrated Discovery database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A "Target-Pathway" network was created by using Cytoscape 3.9.1. The RNA and protein expression levels of core target genes were observed using the Cancer Genome Atlas and the Human Protein Atlas databases. DriverDBv3 and Timer2.0 databases were used for survival and immune infiltration analysis. Subsequently, the findings were further verified by molecular docking technology and in vitro experiments. RESULTS: A total of 378 resveratrol action targets and 2154 GC disease targets were obtained from public databases, and 181 intersection targets between the two were screened by Venn diagram. The top 20 core targets were identified by PPI network analysis of the overlapping targets. GO function analysis mainly involved protein binding, identical protein binding, cytoplasm, nucleus, negative regulation of apoptotic process and response to xenobiotic stimulus. KEGG enrichment analysis suggested that the involved signaling pathways mainly included PI3K-AKT signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, TNF signaling pathway, ErbB signaling pathway, etc. FBJ murine osteosarcoma viral oncogene homolog (FOS) and matrix metallopeptidase 9 (MMP9) were selected by differential expression analysis, and they were closely associated with immune infiltration. Molecular docking results showed that resveratrol docked well with these two targets. Resveratrol treatment arrested the cell cycle at the S phase, induced apoptosis, and weakened viability, migration and invasion in a dose-dependent manner. Furthermore, resveratrol could exhibit anti-GC effect by regulating FOS and MMP9 expression. CONCLUSION: The anti-GC effects of resveratrol are related to the inhibition of cell proliferation, migration, invasion and induction of cell cycle arrest and apoptosis by targeting FOS and MMP9.

4.
Sensors (Basel) ; 24(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38475087

RESUMO

In smart cities, bicycle-sharing systems have become an essential component of the transportation services available in major urban centers around the globe. Due to environmental sustainability, research on the power-assisted control of electric bikes has attracted much attention. Recently, fuzzy logic controllers (FLCs) have been successfully applied to such systems. However, most existing FLC approaches have a fixed fuzzy rule base and cannot adapt to environmental changes, such as different riders and roads. In this paper, a modified FLC, named self-tuning FLC (STFLC), is proposed for power-assisted bicycles. In addition to a typical FLC, the presented scheme adds a rule-tuning module to dynamically adjust the rule base during fuzzy inference processes. Simulation and experimental results indicate that the presented self-tuning module leads to comfortable and safe riding as compared with other approaches. The technique established in this paper is thought to have the potential for broader application in public bicycle-sharing systems utilized by a diverse range of riders.

5.
Planta ; 259(5): 104, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38551672

RESUMO

MAIN CONCLUSION: The post-transcriptional gene regulatory pathway and small RNA pathway play important roles in regulating the rapid and long-term response of Rhododendron moulmainense to high-temperature stress. The Rhododendron plays an important role in maintaining ecological balance. However, it is difficult to domesticate for use in urban ecosystems due to their strict optimum growth temperature condition, and its evolution and adaptation are little known. Here, we combined transcriptome and small RNAome to reveal the rapid response and long-term adaptability regulation strategies in Rhododendron moulmainense under high-temperature stress. The post-transcriptional gene regulatory pathway plays important roles in stress response, in which the protein folding pathway is rapidly induced at 4 h after heat stress, and alternative splicing plays an important role in regulating gene expression at 7 days after heat stress. The chloroplasts oxidative damage is the main factor inhibiting photosynthesis efficiency. Through WGCNA analysis, we identified gene association patterns and potential key regulatory genes responsible for maintaining the ROS steady-state under heat stress. Finally, we found that the sRNA synthesis pathway is induced under heat stress. Combined with small RNAome, we found that more miRNAs are significantly changed under long-term heat stress. Furthermore, MYBs might play a central role in target gene interaction network of differentially expressed miRNAs in R. moulmainense under heat stress. MYBs are closely related to ABA, consistently, ABA synthesis and signaling pathways are significantly inhibited, and the change in stomatal aperture is not obvious under heat stress. Taken together, we gained valuable insights into the transplantation and long-term conservation domestication of Rhododendron, and provide genetic resources for genetic modification and molecular breeding to improve heat resistance in Rhododendron.


Assuntos
MicroRNAs , Rhododendron , Transcriptoma/genética , Rhododendron/genética , Rhododendron/metabolismo , Ecossistema , Resposta ao Choque Térmico/genética , MicroRNAs/genética , Perfilação da Expressão Gênica
6.
Chem Biol Interact ; 393: 110947, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38479716

RESUMO

In this study, twenty-nine coumarin-3-sulfonamide derivatives, twenty-seven of which are original were designed and synthesized. Cytotoxicity assay indicated that most of these derivatives exhibited moderated to good potency against A549 cells. Among them, compound 8q showed potent inhibition against the four tested cancer cell lines, especially A549 cells with IC50 value of 6.01 ± 0.81 µM, and much lower cytotoxicity on the normal cells was observed compared to the reference compounds. Bioinformatics analysis revealed human carbonic anhydrase IX (CAIX) was highly expressed in lung adenocarcinoma (LUAD) and associated with poor prognosis. The inhibitory activity of compound 8q against CAIX was assessed by using molecular docking and molecular dynamics simulations, which revealed prominent interactions of both compound 8q and CAIX at the active site and their high affinity. The results of ELISA assays verified that compound 8q possessed strong inhibitory activity against CAIX and high subtype selectivity, and could also down-regulate the expression of CAIX in A549 cells. Furthermore, the significant inhibitory effects of compound 8q on the migration and invasion of A549 cells were also found. After treatment with compound 8q, intracellular reactive oxygen species (ROS) levels increased and mitochondrial membrane potential (MMP) decreased. Mechanistic investigation using western blotting revealed compound 8q exerted the anti-migrative and anti-invasive effects probably through mitochondria-mediated PI3K/AKT pathway by targeting CAIX. In summary, coumarin-3-sulfonamide derivatives were developed as potential and effective CAIX inhibitors, which were worthy of further investigation.


Assuntos
Inibidores da Anidrase Carbônica , Cumarínicos , Humanos , Anidrase Carbônica IX , Simulação de Acoplamento Molecular , Cumarínicos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Antígenos de Neoplasias/metabolismo , Sulfonamidas/farmacologia , Relação Estrutura-Atividade , Estrutura Molecular
7.
Adv Mater ; : e2400690, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38373436

RESUMO

The stable phase transformation during electrochemical progress drives extensive research on vanadium-based polyanions in sodium-ion batteries (SIBs), especially Na3 V2 (PO4 )3 (NVP). And the electron transfer between V3+/4+ redox couple in NVP could be generally achieved, owing to the confined crystal variation during battery service. However, the more favorable V4+/5+ redox couple is still in hard-to-access situation due to the high barrier and further brings about the corresponding inefficiency in energy densities. In this work, the multilevel redox in NVP frame (MLNP) alters reaction pathway to undergo homeostatic solid solution process and breaks the high barrier of V4+/5+ at high voltage, taking by progressive transition metal (V, Fe, Ti, and Cr) redox couple. The diversified reaction paths across diffusion barriers could be realized by distinctive release/uptake of inactive Na1 site, confirmed by the calculations of density functional theory. Thereby its volume change is merely 1.73% during the multielectron-transfer process (≈2.77 electrons). MLNP cathode could achieve an impressive energy density of 440 Wh kg-1 , driving the leading development of MLNP among other NASICON structure SIBs. The integration of multiple redox couples with low strain modulates the reaction pathway effectively and will open a new avenue for fabricating high-performance cathodes in SIBs.

8.
Nat Commun ; 15(1): 1757, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413612

RESUMO

Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection.


Assuntos
Candida albicans , Proteínas Fúngicas , Humanos , Camundongos , Animais , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Candida albicans/metabolismo , Peptídeos/metabolismo
9.
Acta Pharmacol Sin ; 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409216

RESUMO

Alzheimer's disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia in elderly people and substantially affects patient quality of life. Oxidative stress is considered a key factor in the development of AD. Nrf2 plays a vital role in maintaining redox homeostasis and regulating neuroinflammatory responses in AD. Previous studies show that potassium 2-(1-hydroxypentyl)-benzoate (PHPB) exerts neuroprotective effects against cognitive impairment in a variety of dementia animal models such as APP/PS1 transgenic mice. In this study we investigated whether PHPB ameriorated the progression of AD by reducing oxidative stress (OS) damage. Both 5- and 13-month-old APP/PS1 mice were administered PHPB (100 mg·kg-1·d-1, i.g.) for 10 weeks. After the cognition assessment, the mice were euthanized, and the left hemisphere of the brain was harvested for analyses. We showed that 5-month-old APP/PS1 mice already exhibited impaired performance in the step-down test, and knockdown of Nrf2 gene only slightly increased the impairment, while knockdown of Nrf2 gene in 13-month-old APP/PS1 mice resulted in greatly worse performance. PHPB administration significantly ameliorated the cognition impairments and enhanced antioxidative capacity in APP/PS1 mice. In addition, PHPB administration significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the expression levels of Nrf2, HO-1 and NQO-1 in APP/PS1 mice, but these changes were abolished by knockdown of Nrf2 gene. In SK-N-SH APPwt cells and primary mouse neurons, PHPB (10 µM) significantly increased the p-AKT/AKT and p-GSK3ß/GSK3ß ratios and the level of Nrf2, which were blocked by knockdown of Nrf2 gene. In summary, this study demonstrates that PHPB exerts a protective effect via the Akt/GSK3ß/Nrf2 pathway and it might be a promising neuroprotective agent for the treatment of AD.

10.
Sci Rep ; 14(1): 4059, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374235

RESUMO

Research on switchable chaotic systems with a large range of parameters is scarce. To explore the chaotic characteristics of such systems, this paper proposes new switchable methods by modifying the nonlinear term in the system, resulting in a chaotic system with different nonlinear terms. The unknown parameters in the nonlinear term exhibit different numerical relationships under various combined conditions, and some parameters may tend towards positive infinity. The chaos characteristics are verified by applying a specific switching method to the unified chaotic system. The pseudo-randomness of the random sequence generated by the dissipative system is verified using the NIST test. Finally, the circuit simulation of the system under various switching conditions is performed by selecting different circuit components and adjusting the resistance values.The switching chaotic system is implemented physically on FPGA and breadboard, and the effectiveness of the system is verified.

11.
Front Microbiol ; 15: 1296753, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38380100

RESUMO

Dental fluorosis, resulting from long-term environmental exposure to fluoride, is prevalent among diverse populations worldwide. Severe fluorosis not only compromises the aesthetic appeal of teeth but also impairs their functionality. This study aims to investigate the oral microbiome in dental fluorosis and the health individuals of adolescents living in the endemic fluorosis area of Guizhou, China through full-length 16S rDNA sequencing. Fourty-six individuals meet the sampling criteria, and we divided these samples into the following groups: a healthy group (H = 23) and a dental fluorosis group (F = 23), and two subgroups of Miao ethnicity: a healthy Miao group (Hm = 13) and a dental fluorosis Miao group (Fm = 15). A total of 660,389 high-quality sequences were obtained, and 12,007 Amplicon Sequence Variants (ASVs) were identified, revealing significant variations in oral microbiome between Fm and Hm groups. The composition of oral microbiota was similar between the H and F groups. At the genus level, Pseudopropionibacterium and at the species level, Streptococcus oralis_subsp.dentisani_clade_058 were less abundant in group F than in group H (P < 0.05). Further analysis revealed that the abundance of Capnocytophaga gingivalis and Kingella denitrificans was significantly lower in Fm fluorosis patients than in the Hm group (P < 0.05). Based on the LEfSe analysis, the potential core biomarkers in the oral of Fm fluorosis patients were identified at different taxonomic levels, ranging from phylum to species. These include Gammaproteobacteria, Prevotella sp_HMT_304, Gemella sanguinis, and Gracilibacteria_(GN02). Network analysis revealed that the microbiota in the fluorosis group exhibited more complex interactions with each other than the healthy group. Notably, within the Hm group, the potential biomarkers Capnocytophaga gingivalis and Kingella denitrificans exhibited a positive correlation. Finally, we employed PICRUSt2 analysis to explore the abundance clustering of the top 30 functional units in each sample, and we found that the metabolic pathway compositions of the four groups were similar. In summary, our findings suggest that the microbial composition of plaque in Hm patients with dental fluorosis is significantly altered, and we identified the potential marker microorganisms that contribute to these changes.

12.
Phys Rev E ; 109(1-1): 014607, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38366469

RESUMO

The unique ability of fire ants to form a raft to survive flooding rain has enchanted biologists as well as researchers in other disciplines. It was established during the last decade that a three-dimensional aggregation of fire ants exhibits viscoelasticity with respect to external compression and shearing among numerous unusual mechanical properties. Continuing these works, we will study the ant raft in its natural form, i.e., composing no more than two layers. This allowed us to focus on the cracks that are unique to membranes and see how their patterns are influenced by the fact that these ants are mobile and can self-repair the damage to keep their raft from disintegration. In the beginning, we show that vertical and horizontal shaking can also prompt fire ants to aggregate. The canonical view that the stability of ant raft relies on the Cheerios effect and a combination of other parameters is tested. The force-displacement experiment is performed to show that two distinct mechanical responses and fracture patterns, characteristic of ductile and brittle materials, can be elicited, depending on the magnitude of the pull speed. During the process, we counted the number of ants that actively participated in the stress-strain relation and used this information to roughly sketch out the force chain. The latter information reveals that the pull force expedites the alignment of fire ants, in analogy to the effect of an electric field on liquid crystal polymers. To highlight the self-healing nature, we employ the creep experiment to study how the length and Young's modulus of the raft change or relax with time. One major finding is that the raft can exhibit zero Poisson's ratio without resorting to specific geometry structures. This is enabled by the active recruitment of ants from the top layer to the bottom layer to keep the raft from disintegrating.

13.
Nat Commun ; 15(1): 143, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38168066

RESUMO

Extracellular matrix (ECM) assembly/disassembly is a critical regulator for airway epithelial development and remodeling. Airway organoid is widely used in respiratory research, yet there is limited study to indicate the roles and mechanisms of ECM organization in epithelial growth and differentiation by using in vitro organoid system. Moreover, most of current Matrigel-based airway organoids are in basal-out orientation where accessing the apical surface is challenging. We present a human apical-out airway organoid using a biochemically defined hybrid hydrogel system. During human nasal epithelial progenitor cells (hNEPCs) differentiation, the gel gradually degrade, leading to the organoid apical surfaces facing outward. The expression and activity of ECM-degrading enzymes, matrix metalloproteinases (MMP7, MMP9, MMP10 and MMP13) increases during organoid differentiation, where inhibition of MMPs significantly suppresses the normal ciliation, resulting in increased goblet cell proportion. Moreover, a decrease of MMPs is found in goblet cell hyperplastic epithelium in inflammatory mucosa. This system reveals essential roles of epithelial-derived MMPs on epithelial cell fate determination, and provides an applicable platform enabling further study for ECM in regulating airway development in health and diseases.


Assuntos
Células Epiteliais , Organoides , Humanos , Células Epiteliais/metabolismo , Organoides/metabolismo , Metaloproteinases da Matriz/metabolismo , Células Caliciformes/metabolismo , Células-Tronco/metabolismo , Matriz Extracelular/metabolismo
14.
Histol Histopathol ; 39(1): 91-104, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37042618

RESUMO

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is suggested before resection surgery in the control of rectal cancer. Unfortunately, treatment outcomes are widely variable and highly patient-specific. Notably, rectal cancer patients with distant metastasis generally have a much lower survival rate. Accordingly, a better understanding of the genetic background of patient cohorts can aid in predicting CCRT efficacy and clinical outcomes for rectal cancer before distant metastasis. METHODS: A published transcriptome dataset (GSE35452) (n=46) was utilized to distinguish prospective genes concerning the response to CCRT. We recruited 172 rectal cancer patients, and the samples were collected during surgical resection after CCRT. Immunohistochemical (IHC) staining was performed to evaluate the expression level of regenerating family member 3 alpha (REG3A). Pearson's chi-squared test appraised the relevance of REG3A protein expression to clinicopathological parameters. The Kaplan-Meier method was utilized to generate survival curves, and the log-rank test was performed to compare the survival distributions between two given groups. RESULTS: Employing a transcriptome dataset (GSE35452) and focusing on the inflammatory response (GO: 0006954), we recognized that REG3A is the most significantly upregulated gene among CCRT nonresponders (log2 ratio=1.2472, p=0.0079). Following IHC validation, high immunoexpression of REG3A was considerably linked to advanced post-CCRT tumor status (p<0.001), post-CCRT lymph node metastasis (p=0.042), vascular invasion (p=0.028), and low-grade tumor regression (p=0.009). In the multivariate analysis, high immunoexpression of REG3A was independently correlated with poor disease-specific survival (DSS) (p=0.004) and metastasis-free survival (MeFS) (p=0.045). The results of the bioinformatic analysis also supported the idea that REG3A overexpression is implicated in rectal carcinogenesis. CONCLUSION: In the current study, we demonstrated that REG3A overexpression is correlated with poor CCRT effectiveness and inferior patient survival in rectal cancer. The predictive and prognostic utility of REG3A expression may direct patient stratification and decision-making more accurately for those patients.


Assuntos
Biomarcadores Tumorais , Neoplasias Retais , Humanos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Quimiorradioterapia , Prognóstico , Estudos Prospectivos , Neoplasias Retais/genética , Neoplasias Retais/terapia
15.
Nucleic Acids Res ; 52(D1): D376-D383, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37870448

RESUMO

Allosteric regulation, induced by perturbations at an allosteric site topographically distinct from the orthosteric site, is one of the most direct and efficient ways to fine-tune macromolecular function. The Allosteric Database (ASD; accessible online at http://mdl.shsmu.edu.cn/ASD) has been systematically developed since 2009 to provide comprehensive information on allosteric regulation. In recent years, allostery has seen sustained growth and wide-ranging applications in life sciences, from basic research to new therapeutics development, while also elucidating emerging obstacles across allosteric research stages. To overcome these challenges and maintain high-quality data center services, novel features were curated in the ASD2023 update: (i) 66 589 potential allosteric sites, covering > 80% of the human proteome and constituting the human allosteric pocketome; (ii) 748 allosteric protein-protein interaction (PPI) modulators with clear mechanisms, aiding protein machine studies and PPI-targeted drug discovery; (iii) 'Allosteric Hit-to-Lead,' a pioneering dataset providing panoramic views from 87 well-defined allosteric hits to 6565 leads and (iv) 456 dualsteric modulators for exploring the simultaneous regulation of allosteric and orthosteric sites. Meanwhile, ASD2023 maintains a significant growth of foundational allosteric data. Based on these efforts, the allosteric knowledgebase is progressively evolving towards an integrated landscape, facilitating advancements in allosteric target identification, mechanistic exploration and drug discovery.


Assuntos
Sítio Alostérico , Bases de Conhecimento , Humanos , Regulação Alostérica , Descoberta de Drogas , Ligantes , Proteoma , Mapas de Interação de Proteínas
16.
Chem Rev ; 124(1): 164-209, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38044580

RESUMO

The performance of a chemical reaction is critically dependent on the electronic and/or geometric structures of a material in heterogeneous catalysis. Over the past century, the Sabatier principle has already provided a conceptual framework for optimal catalyst design by adjusting the electronic structure of the catalytic material via a change in composition. Beyond composition, it is essential to recognize that the geometric atomic structures of a catalyst, encompassing terraces, edges, steps, kinks, and corners, have a substantial impact on the activity and selectivity of a chemical reaction. Crystal-phase engineering has the capacity to bring about substantial alterations in the electronic and geometric configurations of a catalyst, enabling control over coordination numbers, morphological features, and the arrangement of surface atoms. Modulating the crystallographic phase is therefore an important strategy for improving the stability, activity, and selectivity of catalytic materials. Nonetheless, a complete understanding of how the performance depends on the crystal phase of a catalyst remains elusive, primarily due to the absence of a molecular-level view of active sites across various crystal phases. In this review, we primarily focus on assessing the dependence of catalytic performance on crystal phases to elucidate the challenges and complexities inherent in heterogeneous catalysis, ultimately aiming for improved catalyst design.

17.
Artigo em Inglês | MEDLINE | ID: mdl-38075530

RESUMO

Background: Ossicles of avulsed fractures of the lateral malleolus can result in pain or chronic ankle instability. The purpose of this study was to evaluate and compare the arthroscopic double-row fixation procedure with anatomic ankle lateral ligaments reconstruction for the treatment of ankle lateral ligaments injury with os subfibulare. Methods: This retrospective study included 38 patients with ankle lateral ligaments injury with concomitant os subfibulare who were treated between July 2016 and November 2021. The patients were divided into a double-row fixation group (n = 19) and an ankle lateral ligaments reconstruction group (n = 19). The Karlsson and Peterson Scoring System for Ankle Function (KAFS), American Orthopedic Foot and Ankle Society (AOFAS) score, Tegner score, visual analog scale (VAS), and anterior drawer test (ADT) were obtained preoperatively and at the last post-operative follow-up. Magnetic resonance imaging (MRI) was also performed at the last post-operative follow-up. Results: The KAFS, AOFAS, VAS, and Tegner scores increased significantly after the surgery. Furthermore, the pre- and post-operative functional scores were comparable between the two groups. The ADT was negative in all participants post-operatively. There were no significant differences between the double-row fixation and ligaments reconstruction groups regarding the proportions of patients who achieved a minimally clinically important difference (MCID) in KAFS, AOFAS, and Tegner scores. There was no significant difference in T2 mapping values for the tibial and talar side post-operatively between the two groups. Moreover, there were no significant differences in functional scores post-operatively between bony fusion and non-fusion patients in the double fixation group. Conclusion: The double-row fixation procedure provided similar satisfactory clinical outcomes when compared with lateral ligaments reconstruction for the treatment of ankle lateral ligaments injury with os subfibulare over a short follow-up duration.

18.
Plants (Basel) ; 12(23)2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38068620

RESUMO

The role of melatonin in plant growth and response to environmental stress has been widely demonstrated. However, the physiological and molecular regulation of salt tolerance in wheat seedlings by melatonin remains unclear. In this study, we investigated changes in phenotype, physiology, photosynthetic parameters, and transcript levels in wheat seedlings to reveal the role of melatonin in the regulation of salt tolerance in wheat. The results indicate that the application of exogenous melatonin significantly alleviates growth inhibition, reactive oxygen species accumulation, and membrane oxidative damage induced by salt stress in wheat. Additionally, exogenous melatonin increased antioxidant enzyme activity and regulated photosynthetic gas exchange. Transcriptomic data showed a significant up-regulation of genes encoding light-harvesting chlorophyll protein complex proteins in photosynthesis and genes related to chlorophyll and carotenoid biosynthesis under the influence of melatonin. These results suggest that exogenous melatonin improves salt tolerance in wheat seedlings by enhancing the antioxidant, photoprotective, and photosynthesis activities.

19.
Eur J Med Res ; 28(1): 593, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38102624

RESUMO

Cholangiocarcinoma is the most common malignant bile duct tumor in Southeast Asia. The special location of cholangiocarcinoma leads to it being difficult to diagnose. Currently, the progress in clinical prognosis outcomes remains abysmal owing to the lack of definitive diagnostic criteria. Therefore, uncovering the potential markers for cholangiocarcinoma is a pressing issue. Ubiquitin-conjugating enzyme E2 C (UBE2C) is a critical ubiquitination enzyme; it is involved in the tumorigenesis of various malignancies and affects the patient's prognosis. However, there is currently no relevant literature to indicate whether UBE2C is related to the clinical survival outcome of cholangiocarcinoma patients. In this report, we mined the published cholangiocarcinoma transcriptome data set (GSE26566), compared it with the ubiquitination-associated gene (GO:0016567), and identified that UBE2C was highly expressed in cholangiocarcinoma tumor tissue. Moreover, high expression of UBE2C was markedly correlated with surgical margin, primary tumor, histological variants, and histological grade. More specifically, high expression of UBE2C was negatively associated with overall survival, disease-specific survival, local recurrence-free survival, and metastasis-free survival in patients with cholangiocarcinoma. Our findings demonstrate that UBE2C may provide a potential therapeutic marker and prognostic factor for cholangiocarcinoma patients.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Prognóstico , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismo , Colangiocarcinoma/genética , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/genética , Ductos Biliares Intra-Hepáticos/metabolismo
20.
PLoS One ; 18(12): e0281619, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38127947

RESUMO

The sustainable development of mycorrhizal industry is the key to solve the problem of "mycorrhizal forestry contradiction". As a major province of edible mushroom production and forestry resources in China, Fujian Province is also an important origin of mycorrhizal technology research and development, so it is more typical and practical to establish an index system to evaluate the sustainability of mycorrhizal industry development in Fujian Province. Through research interviews and data collection, a sustainable capacity evaluation system of mycorrhizal industry was established with 21 indicators in six dimensions: economic, ecological, social, cultural, political, and technological. A combination of CRITIC empowerment method and cloud model was used to evaluate the sustainability of mycorrhizal industry development in Fujian Province. The results show that although the economic sustainability of the mycorrhizal industry in Fujian Province is average, the overall development trend is good and there are not too many problems. The sustainability of ecological, social and technological levels all have large differences in the development of indicators and the overall development status is average, but overall, the ecological, social and technological levels show a steady forward development from 2017 to 2020. The cultural and political dimensions of sustainability not only have large differences in the development of indicators and an average overall development status, but also have a small development span from 2017 to 2020 and a slow overall development.


Assuntos
Desenvolvimento Industrial , Desenvolvimento Sustentável , Indústrias , Tecnologia , China , Conservação dos Recursos Naturais
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