RESUMO

Casuarina equisetifolia trees are used as windbreaks in subtropical and tropical coastal zones, while C. equisetifolia windbreak forests can be degraded by seawater atomization (SA) and seawater encroachment (SE). To investigate the mechanisms underlying the response of C. equisetifolia to SA and SE stress, the transcriptome and metabolome of C. equisetifolia seedlings treated with control, SA, and SE treatments were analyzed. We identified 737, 3232, 3138, and 3899 differentially expressed genes (SA and SE for 2 and 24 h), and 46, 66, 62, and 65 differentially accumulated metabolites (SA and SE for 12 and 24 h). The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that SA and SE stress significantly altered the expression of genes related to plant hormone signal transduction, plant-pathogen interaction, and starch and sucrose metabolism pathways. The accumulation of metabolites associated with the biosynthetic pathways of phenylpropanoid and amino acids, as well as starch and sucrose metabolism, and glycolysis/gluconeogenesis were significantly altered in C. equisetifolia subjected to SA and SE stress. In conclusion, C. equisetifolia responds to SA and SE stress by regulating plant hormone signal transduction, plant-pathogen interaction, biosynthesis of phenylpropanoid and amino acids, starch and sucrose metabolism, and glycolysis/gluconeogenesis pathways. Compared with SA stress, C. equisetifolia had a stronger perception and response to SE stress, which required more genes and metabolites to be regulated. This study enhances our understandings of how C. equisetifolia responds to two types of seawater stresses at transcriptional and metabolic levels. It also offers a theoretical framework for effective coastal vegetation management in tropical and subtropical regions.

Assuntos

Água do Mar , Estresse Fisiológico , Estresse Fisiológico/genética , Água do Mar/química , Transcriptoma , Regulação da Expressão Gênica de Plantas , Metaboloma , Plântula/genética , Plântula/fisiologia , Metabolômica , Multiômica

RESUMO

BACKGROUND: Periodontitis, a persistent inflammatory condition, significantly impairs individuals' overall quality of life. Lymphocyte-to-high-density lipoprotein cholesterol ratio (LHR), monocyte-to-high-density lipoprotein cholesterol ratio (MHR), neutrophil-to-high-density lipoprotein cholesterol ratio (NHR), and platelet-to-high-density lipoprotein cholesterol ratio (PHR) are new convenient and economical biomarkers. However, whether the above high-density lipoprotein-related inflammatory biomarkers are associated with periodontitis has rarely been investigated. Therefore, the research endeavor focused on uncovering potential relationships. METHODS: The research encompassed a diverse and extensive sample, comprising 9,470 participants, selected from the National Health and Nutrition Examination Survey spanning the years 2009 to 2014. The association between high-density lipoprotein-related inflammatory biomarkers and periodontitis was explored utilizing a multivariable logistic regression model with weighted analysis. Additionally, the study employed smoothed curve fitting to explore potential nonlinear relationships. Further stratified analyses and interaction tests were performed. RESULTS: This study indicated no apparent association between MHR and PHR with periodontitis, whereas LHR and NHR demonstrated a statistically significant positive relationship with the prevalence of periodontitis. In the fully adjusted model, participants belonging to the highest tertile of both LHR and NHR showed a notably higher likelihood of having periodontitis compared to those in the lowest tertile (LHR: OR = 1.22, 95% CI: 1.06, 1.39; NHR: OR = 1.27, 95% CI: 1.09, 1.49). Furthermore, smooth curve fitting was employed to investigate the potential nonlinear relationship between LHR, NHR, and periodontitis. The results indicated that there was a significant increase in the occurrence of periodontitis when Log2 (LHR) exceeded 1.01 and Log2(NHR) surpassed 2.16 (Log2(LHR): OR = 1.42; 95% CI: 1.19, 1.69; Log2(NHR): OR = 1.40; 95% CI: 1.15, 1.71). The subgroup analysis revealed that the associations between periodontitis and either LHR or NHR, separately, were more pronounced among individuals under the age of 50 and those without hypertension. CONCLUSIONS: This cross-sectional study revealed a positive relationship between LHR、NHR and periodontitis, particularly when these indicators exceeded their thresholds. LHR and NHR may serve as potential inflammatory markers for identifying periodontitis, thereby facilitating early warning for both patients and dentists, and enabling early intervention in the oral environment. Besides, extensive prospective cohort investigations are essential to confirm and solidify this observation.

Assuntos

Biomarcadores , Inflamação , Inquéritos Nutricionais , Periodontite , Humanos , Periodontite/sangue , Periodontite/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Inflamação/sangue , Biomarcadores/sangue , HDL-Colesterol/sangue , Monócitos/metabolismo , Neutrófilos , Idoso , Linfócitos/metabolismo , Lipoproteínas HDL/sangue , Estudos Transversais , Plaquetas/patologia , Modelos Logísticos

RESUMO

Recent observations have revealed upregulation of H3K27cr in colorectal cancer (CRC) tissues; however, the underlying cause remains elusive. This study aimed to investigate the mechanism of H3K27cr upregulation and its roles in CRC metastasis. Clinically, our findings showed that H3K27cr served as a highly accurate diagnostic marker to distinguish CRC tissues from healthy controls. Elevated levels of LINC00887 and H3K27cr were associated with a poorer prognosis in CRC patients. Functionally, LINC00887 and H3K27cr facilitated the migration and invasion of CRC cells. Mechanistically, LINC00887 interacted with SIRT3 protein. Overexpressed of LINC00887 obstructed the enrichment of SIRT3 within GCN5 promoter, thereby elevating H3K27ac but not H3K27cr level within this region, subsequently activating GCN5 expression. This activation increased the global level of H3K27cr, promoting the enrichment of GCN5, H3K27cr, and YEATS2 within ETS1 promoter, activating ETS1 transcription and ultimately promoting the metastasis of CRC. The in vivo study demonstrated that inhibition of LINC00887 suppressed CRC metastasis, but this inhibitory effect was nullified when mice were treated with NaCr. In conclusion, our results confirmed the diagnostic biomarker potential of H3K27cr in individuals with CRC, and proposed a functional model to elucidate the involvement of LINC00887 in promoting CRC metastasis by elevating H3K27cr level.

Assuntos

Neoplasias Colorretais , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Proteína Proto-Oncogênica c-ets-1 , RNA Longo não Codificante , Fatores de Transcrição de p300-CBP , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Proteína Proto-Oncogênica c-ets-1/metabolismo , Proteína Proto-Oncogênica c-ets-1/genética , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fatores de Transcrição de p300-CBP/metabolismo , Fatores de Transcrição de p300-CBP/genética , Camundongos , Metástase Neoplásica , Linhagem Celular Tumoral , Masculino , Movimento Celular/genética , Feminino , Camundongos Endogâmicos BALB C , Sirtuína 3/metabolismo , Sirtuína 3/genética , Regiões Promotoras Genéticas/genética , Histonas/metabolismo , Pessoa de Meia-Idade

RESUMO

The widespread use of Chat Generative Pre-trained Transformer (known as ChatGPT) and other emerging technology that is powered by generative artificial intelligence (GenAI) has drawn attention to the potential ethical issues they can cause, especially in high-stakes applications such as health care, but ethical discussions have not yet been translated into operationalisable solutions. Furthermore, ongoing ethical discussions often neglect other types of GenAI that have been used to synthesise data (eg, images) for research and practical purposes, which resolve some ethical issues and expose others. We did a scoping review of the ethical discussions on GenAI in health care to comprehensively analyse gaps in the research. To reduce the gaps, we have developed a checklist for comprehensive assessment and evaluation of ethical discussions in GenAI research. The checklist can be integrated into peer review and publication systems to enhance GenAI research and might be useful for ethics-related disclosures for GenAI-powered products and health-care applications of such products and beyond.

RESUMO

The morbidity and mortality of cancer are rising rapidly worldwide and immunotherapy has become an effective means to curb the progress of cancer. Sirtuin-1(SIRT1) is a NAD+ -dependent deacetylase that plays a key role in cancer development and immune regulation through mediating a variety of signaling pathways. Targeting SIRT1 in immunotherapy could enhance or erod immune responses against cancer cells, while SIRT1 activator and inhibitors are being developed as potential antineoplastic agents with important implications in clinic. This review summarizes the impact of SIRT1 in different types of immune cells and mechanism of SIRT1-mediated immune responses in tumor progression as well as its therapeutic perspectives.

RESUMO

As the most abundant renewable carbon source, lignocellulose holds potential as a raw material for biofuels and biochar. The components required for biofuel production differ from those for biochar, so combining processes can reduce costs. Biofuel preparation necessitates cellulase treatment of lignocellulose. This study examines the effects of various enzyme treatment conditions (dosage, time, temperature) on lignocellulose, focusing on the properties of biochar derived from it (BC-SR). A mathematical model was constructed to study the relationship between enzyme treatment conditions and BC-SR properties. BC-SR exhibited high adsorption selectivity for bisphenol A and outperformed untreated biochar in fixed-bed column experiments, demonstrating greater removal efficiency and structural integrity. This study provides insights into the impact of enzymatic treatment on biochar and offers a cost-effective method for producing stable, efficient biochar. Additionally, a highly persistent biochar can enter the carbon trading market as a carbon-neutral technology, further realizing economic and environmental benefits.

RESUMO

BACKGROUND: Hematopoietic stem progenitor cells (HSPCs) undergo phenotypical and functional changes during their emergence and development. Although the molecular programs governing the development of human hematopoietic stem cells (HSCs) have been investigated broadly, the relationships between dynamic metabolic alterations and their functions remain poorly characterized. METHODS: In this study, we comprehensively described the proteomics of HSPCs in the human fetal liver (FL), umbilical cord blood (UCB), and adult bone marrow (aBM). The metabolic state of human HSPCs was assessed via a Seahorse assay, RT‒PCR, and flow cytometry-based metabolic-related analysis. To investigate whether perturbing glutathione metabolism affects reactive oxygen species (ROS) production, the metabolic state, and the expansion of human HSPCs, HSPCs were treated with buthionine sulfoximine (BSO), an inhibitor of glutathione synthetase, and N-acetyl-L-cysteine (NAC). RESULTS: We investigated the metabolomic landscape of human HSPCs from the fetal, perinatal, and adult developmental stages by in-depth quantitative proteomics and predicted a metabolic switch from the oxidative state to the glycolytic state during human HSPC development. Seahorse assays, mitochondrial activity, ROS level, glucose uptake, and protein synthesis rate analysis supported our findings. In addition, immune-related pathways and antigen presentation were upregulated in UCB or aBM HSPCs, indicating their functional maturation upon development. Glutathione-related metabolic perturbations resulted in distinct responses in human HSPCs and progenitors. Furthermore, the molecular and immunophenotypic differences between human HSPCs at different developmental stages were revealed at the protein level for the first time. CONCLUSION: The metabolic landscape of human HSPCs at three developmental stages (FL, UCB, and aBM), combined with proteomics and functional validations, substantially extends our understanding of HSC metabolic regulation. These findings provide valuable resources for understanding human HSC function and development during fetal and adult life.

Assuntos

Células-Tronco Hematopoéticas , Proteômica , Espécies Reativas de Oxigênio , Humanos , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/citologia , Proteômica/métodos , Espécies Reativas de Oxigênio/metabolismo , Feto/metabolismo , Feto/citologia , Adulto , Sangue Fetal/citologia , Sangue Fetal/metabolismo , Butionina Sulfoximina/farmacologia , Glutationa/metabolismo

RESUMO

At present, hundreds of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been confirmed to be related to the toxicity of cadmium (Cd). However, the role of circular RNAs (circRNAs) in the toxicity of Cd and the underlying regulatory mechanisms remain unclear. In this study, we chose human normal liver cells (L-02) as a model to investigate changes in transcriptome expression levels following exposure to Cd. Total RNA of each sample was extracted by Trizol method, and the expression profiles of circRNAs, miRNAs and mRNAs of each sample were determined by microarray hybridization and scanning. After standardizing the data, differential circRNAs, miRNAs, and mRNAs associated with the toxic effects of Cd were identified. By screening the predicted circRNAs, miRNAs, and mRNAs, we constructed a competing endogenous RNA (ceRNA) network, and predicted the main biological functions and metabolic pathways influenced by Cd toxicity. Our comprehensive screening strategy led to the identification of 266 different circRNAs, 223 different miRNAs and 519 different mRNAs exhibiting differential expression. Following further screening, even circRNAs, 10 miRNAs and 97 mRNAs were incorporated into the ceRNA network. After performing GO enrichment and KEGG pathway analyses on the 97 mRNAs within the ceRNA network, which indicated that the circRNAs in the ceRNA network are poised to modulate key cellular processes, including cell proliferation, apoptosis, oxidative stress and inflammatory responses under the toxic effects of Cd-induced damage in L-02 cells.

RESUMO

BACKGROUND: Extragastrointestinal stromal tumors (EGIST) and gastrointestinal stromal tumors are of similar pathological type and form. Here we report a rare case of EGIST diffusely distributed in membranous tissue in abdominal cavity, the feature of which included diffuse tumors at membranous tissue in entire abdominal cavity and spontaneous bleeding of the tumors. CASE SUMMARY: The patient was a 71-year man and hospitalized due to continuous pain at lower abdomen for more than 10 days. Upon physical examination, the patient had flat and tough abdomen with mild pressing pain at lower abdomen, no obvious abdominal mass was touchable, and shifting dullness was positive. Positron emission tomography-computed tomography (CT) showed that in his peritoneal cavity, there were multiple nodules of various sizes, seroperitoneum, multiple enlarged lymph nodes in abdominal/pelvic cavity and right external ilium as well as pulmonary nodules. Plain CT scanning at epigastrium/hypogastrium/pelvic cavity + enhanced three-dimensional reconstruction revealed multiple soft tissue nodules in abdominal/pelvic cavity, peritoneum and right groin. Tumor marker of carbohydrate antigen 125 was 808 U/mL, diffuse tuberous tumor was seen in abdominal/pelvic cavity during operation with hematocelia, and postoperative pathological examination confirmed EGIST. Imatinib was administered with better therapeutic effect. CONCLUSION: Gene testing showed breast cancer susceptibility gene 1 interacting protein C-terminal helicase 1 and KIT genovariation, and the patient was treated with imatinib follow-up visit found that his clinical symptoms disappeared and the tumor load alleviated obviously via imageological examination.

RESUMO

BACKGROUND: Continuous advancements and breakthroughs in flexible gastrointestinal endoscopy have led to alternatives to colonic anastomosis. OBJECTIVE: This study aimed to evaluate the feasibility and safety of end-to-end colonic anastomosis using a single flexible endoscope with the novel through-the-scope "bow-tie" (TTS-BT) device and conventional metal clips in a porcine model. DESIGN: Animal study. SETTINGS: Animal laboratory at China Medical University. PATIENTS: Eight healthy pigs were included. INTERVENTIONS: Eight animals underwent total colonic severance and anastomoses with through-the-scope "bow-tie" devices and metal clips. MAIN OUTCOME MEASURES: The primary outcomes were the success rate of the anastomosis and survival rate during 3-month follow-up. Furthermore, the secondary outcomes were anastomotic site healing, reintervention rate, and rate of anastomotic complications such as bleeding, leakage, stenosis, and obstruction. Six pigs were euthanized, and necropsies were performed 3 months postoperatively, while two pigs were fed for long-term observation. The anastomotic stoma was histologically analyzed using Hematoxylin-eosin and Masson's trichrome staining. RESULTS: End-to-end colonic anastomoses were successfully performed using through-the-scope "bow-tie" devices, and satisfactory healing was achieved in all pigs. The success rate of anastomosis was 100% (8/8). All animals survived postoperatively without anastomotic complications, including bleeding, leakage, or obstruction; however, two cases of stenosis occurred (25%), and one case (12.5%) required reintervention. LIMITATIONS: Large-scale studies should be conducted to verify the feasibility and safety of the through-the-scope "bow-tie" device in other parts of the intestine. CONCLUSIONS: Flexible endoscopy with the through-the-scope "bow-tie" device is feasible and safe for intraluminal colonic anastomosis. This study may expand the indications for full-thickness endoscopic resection in the future. See Video abstract.

RESUMO

Inhibin beta A (INHBA) and its homodimer activin A have pleiotropic effects on modulation of immune responses and tumor progression, but it remains uncertain whether tumors may release activin A to regulate anti-tumor immunity. In this study we investigated the effects and mechanisms of tumor intrinsic INHBA on carcinogenesis, tumor immunity and PD-L1 blockade. Bioinformatic analysis on the TCGA database revealed that INHBA expression levels were elevated in 33 cancer types, including breast cancer (BRCA) and colon adenocarcinoma (COAD). In addition, survival analysis also corroborated that INHBA expression was negatively correlated with the prognosis of many types of cancer patients. We demonstrated that gain or loss function of Inhba did not alter in vitro growth of colorectal cancer CT26 cells, but had striking impact on mouse tumor models including CT26, MC38, B16 and 4T1 models. By using the TIMER 2.0 tool, we figured out that in most cancer types, Inhba expression in tumors was inversely associated with the infiltration of CD4+ T and CD8+ T cells. In CT26 tumor-bearing mice, overexpression of tumor INHBA eliminated the anti-tumor effect of the PD-L1 antibody atezolizumab, whereas INHBA deficiency enhanced the efficacy of atezolizumab. We revealed that tumor INHBA significantly downregulated the interferon-γ (IFN-γ) signaling pathway. Tumor INHBA overexpression led to lower expression of PD-L1 induced by IFN-γ, resulting in poor responsiveness to anti-PD-L1 treatment. On the other hand, decreased secretion of IFN-γ-stimulated chemokines, including C-X-C motif chemokine 9 (CXCL9) and 10 (CXCL10), impaired the infiltration of effector T cells into the tumor microenvironment (TME). Furthermore, the activin A-specific antibody garetosmab improved anti-tumor immunity and its combination with the anti-PD-L1 antibody atezolizumab showed a superior therapeutic effect to monotherapy with garetosmab or atezolizumab. We demonstrate that INHBA and activin A are involved in anti-tumor immunity by inhibiting the IFN-γ signaling pathway, which can be considered as potential targets to improve the responsive rate of PD-1/PD-L1 blockade.

RESUMO

Hematopoietic stem progenitor cells (HSPCs) give rise to the hematopoietic system, maintain hematopoiesis throughout the lifespan, and undergo molecular and functional changes during their development and aging. The importance of hematopoietic stem cell (HSC) biology has led to their extensive characterization at genomic and transcriptomic levels. However, the proteomics of HSPCs throughout the murine lifetime still needs to be fully completed. Here, using mass spectrometry (MS)-based quantitative proteomics, we report on the dynamic changes in the proteome of HSPCs from four developmental stages in the fetal liver (FL) and the bone marrow (BM), including E14.5, young (2 months), middle-aged (8 months), and aging (18 months) stages. Proteomics unveils highly dynamic protein kinetics during the development and aging of HSPCs. Our data identify stage-specific developmental features of HSPCs, which can be linked to their functional maturation and senescence. Our proteomic data demonstrated that FL HSPCs depend on aerobic respiration to meet their proliferation and oxygen supply demand, while adult HSPCs prefer glycolysis to preserve the HSC pool. By functional assays, we validated the decreased mitochondrial metabolism, glucose uptake, reactive oxygen species (ROS) production, protein synthesis rate, and increased glutathione S-transferase (GST) activity during HSPC development from fetal to adult. Distinct metabolism pathways and immune-related pathways enriched in different HSPC developmental stages were revealed at the protein level. Our study will have broader implications for understanding the mechanism of stem cell maintenance and fate determination and reversing the HSC aging process.

RESUMO

Adipose-derived stem cell, one type of mesenchymal stem cells, is a promising approach in treating ischemia-reperfusion injury caused by occlusion of the middle cerebral artery. However, its application has been limited by the complexities of the ischemic microenvironment. Hydrogel scaffolds, which are composed of hyaluronic acid and chitosan, exhibit excellent biocompatibility and biodegradability, making them promising candidates as cell carriers. Vascular endothelial growth factor is a crucial regulatory factor for stem cells. Both hyaluronic acid and chitosan have the potential to make the microenvironment more hospitable to transplanted stem cells, thereby enhancing the therapeutic effect of mesenchymal stem cell transplantation in the context of stroke. Here, we found that vascular endothelial growth factor significantly improved the activity and paracrine function of adipose-derived stem cells. Subsequently, we developed a chitosan-hyaluronic acid hydrogel scaffold that incorporated vascular endothelial growth factor and first injected the scaffold into an animal model of cerebral ischemia-reperfusion injury. When loaded with adipose-derived stem cells, this vascular endothelial growth factor-loaded scaffold markedly reduced neuronal apoptosis caused by oxygen-glucose deprivation/reoxygenation and substantially restored mitochondrial membrane potential and axon morphology. Further in vivo experiments revealed that this vascular endothelial growth factor-loaded hydrogel scaffold facilitated the transplantation of adipose-derived stem cells, leading to a reduction in infarct volume and neuronal apoptosis in a rat model of stroke induced by transient middle cerebral artery occlusion. It also helped maintain mitochondrial integrity and axonal morphology, greatly improving rat motor function and angiogenesis. Therefore, utilizing a hydrogel scaffold loaded with vascular endothelial growth factor as a stem cell delivery system can mitigate the adverse effects of ischemic microenvironment on transplanted stem cells and enhance the therapeutic effect of stem cells in the context of stroke.

RESUMO

The soybean hawkmoth Clanis bilineata tsingtauica Mell (Lepidoptera, Sphingidae; CBT), as one of the main leaf-chewing pests of soybeans, has gained popularity as an edible insect in China recently due to its high nutritional value. However, high-quality genome of CBT remains unclear, which greatly limits further research. In the present study, we assembled a high-quality chromosome-level genome of CBT using PacBio HiFi reads and Hi-C technologies for the first time. The size of the assembled genome is 477.45 Mb with a contig N50 length of 17.43 Mb. After Hi-C scaffolding, the contigs were anchored to 29 chromosomes with a mapping rate of 99.61%. Benchmarking Universal Single-Copy Orthologues (BUSCO) completeness value is 99.49%. The genome contains 252.16 Mb of repeat elements and 14,214 protein-coding genes. In addition, chromosomal synteny analysis showed that the genome of CBT has a strong synteny with that of Manduca sexta. In conclusion, this high-quality genome provides an important resource for future studies of CBT and contributes to the development of integrated pest management strategies.

Assuntos

Genoma de Inseto , Animais , Mariposas/genética , Anotação de Sequência Molecular , Cromossomos de Insetos , Sintenia

RESUMO

In this work, nine new rare-earth metal-organic frameworks (RE-MOFs, where RE=Lu(III), Yb(III), Tm(III), Er(III), Ho(III), Dy(III), Tb(III), Gd(III), and Eu(III)) isostructural to Zr-MOF-808 are synthesized, characterized, and studied regarding their photophysical properties. Materials with high crystallinity and surface area are obtained from a reproducible synthetic procedure that involves the use of two fluorinated modulators. At the same time, these new RE-MOFs display tunable photoluminescent properties due to efficient linker-to-metal energy transfer promoted by the antenna effect, resulting in a series of RE-MOFs displaying lanthanoid-based emissions spanning the visible and near-infrared regions of the electromagnetic spectrum.

RESUMO

The bromodomain and extraterminal domain (BET) family proteins serve as primary readers of acetylated lysine residues and play crucial roles in cell proliferation and differentiation. Dysregulation of BET proteins has been implicated in tumorigenesis, making them important therapeutic targets. BET-bromodomain (BD) inhibitors and BET-targeting degraders have been developed to inhibit BET proteins. In this study, we found that the BET inhibitor MS645 exhibited superior antiproliferative activity than BET degraders including ARV771, AT1, MZ1 and dBET1 in triple-negative breast cancer (TNBC) cells. Treatment with MS645 led to the dissociation of BETs, MED1 and RNA polymerase II from the E2F1-3 promoter, resulting in the suppression of E2F1-3 transcription and subsequent inhibition of cell growth in TNBC. In contrast, while ARV771 displaced BET proteins from chromatin, it did not significantly alter E2F1-3 expression. Mechanistically, ARV771 induced BRD4 depletion at protein level, which markedly increased EGR1 expression. This elevation of EGR1 subsequently recruited septin 2 and septin 9 to E2F1-3 promoters, enhancing E2F1-3 transcription and promoting cell proliferation rate in vitro and in vivo. Our findings provide valuable insights into differential mechanisms of BET inhibition and highlight potential of developing BET-targeting molecules as therapeutic strategies for TNBC.

Assuntos

Proliferação de Células , Fator de Transcrição E2F1 , Proteína 1 de Resposta de Crescimento Precoce , Neoplasias de Mama Triplo Negativas , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Humanos , Proliferação de Células/efeitos dos fármacos , Animais , Fator de Transcrição E2F1/metabolismo , Fator de Transcrição E2F1/genética , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Feminino , Linhagem Celular Tumoral , Fatores de Transcrição E2F/metabolismo , Fatores de Transcrição E2F/genética , Antineoplásicos/farmacologia , Transcrição Gênica/efeitos dos fármacos , Camundongos Nus , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Subunidade 1 do Complexo Mediador/genética , Subunidade 1 do Complexo Mediador/metabolismo , Camundongos , Proteínas que Contêm Bromodomínio , Proteínas de Ciclo Celular , Fator de Transcrição E2F3

RESUMO

Background: Lumbar hernia is a rare disease with low incidence, and no golden standard surgical procedure has been established for lumbar hernias. The single-incision laparoscopic totally extraperitoneal sublay (SIL-TES) technique became a novel surgical technique for lumbar hernias. Methods: This retrospective study included 20 patients who underwent SIL-TES repair for lumbar hernia between April 2020 and March 2024. The baseline patient characteristics, intraoperative data, postoperative data, satisfaction score, and Carolina Comfort Scale scores were collected. Results: The results revealed that the SIL-TES technique for lumbar hernia repair is associated with a low complication rate, nonrecurrence, high satisfaction score, and high quality of life after surgery. Conclusions: The SIL-TES technique could be a feasible and effective surgical technique for lumbar hernias. A controlled study is needed for further confirmation.

Assuntos

Herniorrafia , Laparoscopia , Humanos , Laparoscopia/métodos , Feminino , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Herniorrafia/métodos , Idoso , Adulto , Região Lombossacral/cirurgia , Qualidade de Vida , Resultado do Tratamento

RESUMO

This study aimed to examine the influence of diabetes on the left internal mammary artery (LIMA) and saphenous vein (SV) graft failure for 5-year follow-up. We enrolled 202 patients who underwent isolated off-pump coronary artery bypass grafting (CABG) surgery in 2014, angiographic follow-up occurred at 5 years after surgery. Angiographic outcomes in patients with or without diabetes were analyzed. Multivariate logistic regression analysis was used to identify independent predictors of graft dysfunction. A total of 66 (32.7%) patients had diabetes. Five-year rates of LIMA and SV graft failure were similar in patients with and without diabetes. In addition, in diabetics, the proportion of complete graft failure was significantly lower in the LIMA grafts (12/66, 18.2%) than in the SV grafts (57/133, 42.9%) (P = .001). In nondiabetic, the proportion of complete graft failure was also significantly lower in the LIMA grafts (28/136, 20.6%) than in the SV grafts (105/275, 38.2%) (P < .001). Multivariate logistic regression analysis showed that mean graft flow (MGF) was an independent predictor factor for LIMA (odds ratio = 1.186, 95% CI = 1.114-1.263, P < .001) and SV (odds ratio = 1.056, 95% CI = 1.035-1.077, P < .001) graft failure. Diabetes did not influence the patency of LIMA or SV grafts over a 5-year follow-up. LIMA grafts should be maximized in patients undergoing off-pump CABG surgery. Diabetes does not affect the patency of grafts CABG. Using angiography, our study proved that diabetes does not affect the patency of grafted vessels after CABG for 5 years.

Assuntos

Angiografia Coronária , Ponte de Artéria Coronária sem Circulação Extracorpórea , Artéria Torácica Interna , Grau de Desobstrução Vascular , Humanos , Ponte de Artéria Coronária sem Circulação Extracorpórea/métodos , Masculino , Feminino , Angiografia Coronária/métodos , Pessoa de Meia-Idade , Idoso , Artéria Torácica Interna/transplante , Artéria Torácica Interna/diagnóstico por imagem , Veia Safena/transplante , Veia Safena/diagnóstico por imagem , Diabetes Mellitus/epidemiologia , Oclusão de Enxerto Vascular/epidemiologia , Oclusão de Enxerto Vascular/diagnóstico por imagem , Oclusão de Enxerto Vascular/etiologia , Estudos Retrospectivos , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/diagnóstico por imagem , Seguimentos

RESUMO

Cryo-electron microscopy (cryo-EM) has been widely used to reveal the structures of proteins at atomic resolution. One key challenge is that almost all proteins are predominantly adsorbed to the air-water interface during standard cryo-EM specimen preparation. The interaction of proteins with air-water interface will significantly impede the success of reconstruction and achievable resolution. Here, we highlight the critical role of impenetrable surfactant monolayers in passivating the air-water interface problems, and develop a robust effective method for high-resolution cryo-EM analysis, by using the superstructure GSAMs which comprises surfactant self-assembled monolayers (SAMs) and graphene membrane. The GSAMs works well in enriching the orientations and improving particle utilization ratio of multiple proteins, facilitating the 3.3-Å resolution reconstruction of a 100-kDa protein complex (ACE2-RBD), which shows strong preferential orientation using traditional specimen preparation protocol. Additionally, we demonstrate that GSAMs enables the successful determinations of small proteins (<100 kDa) at near-atomic resolution. This study expands the understanding of SAMs and provides a key to better control the interaction of protein with air-water interface.

Assuntos

Ar , Microscopia Crioeletrônica , Grafite , Água , Microscopia Crioeletrônica/métodos , Água/química , Grafite/química , Tensoativos/química , Proteínas/química , Humanos