RESUMO
Aggregate is one of the most extensive existing modes of matters in the world. Besides the research objectives of inanimate systems in physical science, the entities in life science can be regarded as living aggregates, which are far from being thoroughly understood despite the great advances in molecular biology. Molecular biology follows the research philosophy of reductionism, which generally reduces the whole into parts to study. Although reductionism benefits the understanding of molecular behaviors, it encounters limitations when extending to the aggregate level. Holism is another epistemology comparable to reductionism, which studies objectives at the aggregate level, emphasizing the interactions and synergetic/antagonistic effects of a group of composed single entities in determining the characteristics of a whole. As a representative of holism, aggregation-induced emission (AIE) materials have made great achievements in the past two decades in both physical and life science. In particular, the unique properties of AIE materials endow them with in situ and real-time visual methods to investigate the inconsistency between microscopic molecules and macroscopic substances, offering researchers excellent toolkits to study living aggregates. The applications of AIE materials in life science are still in their infancy and worth expanding. In this Perspective, we summarize the research progress of AIE materials in unveiling some phenomena and processes of living systems, aiming to provide a general research approach from the viewpoint of holism. At last, insights into what we can do in the near future are also raised and discussed.
Assuntos
Biologia Molecular , FilosofiaRESUMO
The CRISPR/Cas12a system is a revolutionary genome editing technique that is widely employed in biosensing and molecular diagnostics. However, there are few reports on precisely managing the trans-cleavage activity of Cas12a by simple modification since the traditional methods to manage Cas12a often require difficult and rigorous regulation of core components. Hence, we developed a novel CRISPR/Cas12a regulatory mechanism, named DNA Robots for Enzyme Activity Management (DREAM), by introducing two simple DNA robots, apurinic/apyrimidinic site (AP site) or nick on target activator. First, we revealed the mechanism of how the DREAM strategy precisely regulated Cas12a through different binding affinities. Second, the DREAM strategy was found to improve the selectivity of Cas12a for identifying base mismatch. Third, a modular biosensor for base excision repair enzymes based on the DREAM strategy was developed by utilizing diversified generation ways of DNA robots, and a multi-signal output platform such as fluorescence, colorimetry, and visual lateral flow strip was constructed. Furthermore, we extended logic sensing circuits to overcome the barrier that Cas12a could not detect simultaneously in a single tube. Overall, the DREAM strategy not only provided new prospects for programmable Cas12a biosensing systems but also enabled portable, specific, and humanized detection with great potential for molecular diagnostics.
Assuntos
Técnicas Biossensoriais , Robótica , Sistemas CRISPR-Cas/genética , Colorimetria , DNA/genética , Reparo por ExcisãoRESUMO
Peptide-based supramolecules exhibit great potential in various fields due to their improved target recognition ability and versatile functions. However, they still suffer from numerous challenges for the biopharmaceutical analysis, including poor self-assembly ability, undesirable ligand-antibody binding rates, and formidable target binding barriers caused by ligand crowding. To tackle these issues, a "polyvalent recognition" strategy employing the CD20 mimotope peptide derivative NBD-FFVLR-GS-WPRWLEN (acting on the CDR domains of rituximab) was proposed to develop supramolecular nanofibers for target antibody recognition. These nanofibers exhibited rapid self-assembly within only 1 min and robust stability. Their binding affinity (179 nM) for rituximab surpassed that of the monomeric peptide (7 µM) by over 38-fold, highlighting that high ligand density and potential polyvalent recognition can efficiently overcome the target binding barriers of traditional supramolecules. Moreover, these nanofibers exhibited an amazing "instantaneous capture" rate (within 15 s), a high recovery (93 ± 3%), and good specificity for the target antibody. High-efficiency enrichment of rituximab was achieved from cell culture medium with good recovery and reproducibility. Intriguingly, these peptide nanofibers combined with bottom-up proteomics were successful in tracking the deamidation of asparagine 55 (from 10 to 16%) on the rituximab heavy chain after 21 day incubation in human serum. In summary, this study may open up an avenue for the development of versatile mimotope peptide supramolecules for biorecognition and bioanalysis of biopharmaceuticals.
Assuntos
Produtos Biológicos , Nanofibras , Humanos , Rituximab , Nanofibras/química , Ligantes , Reprodutibilidade dos Testes , Peptídeos/químicaRESUMO
The use of membrane-based guided bone regeneration techniques has great potential for single-stage reconstruction of critical-sized bone defects. Here, a multifunctional bone regeneration membrane combining flexible elasticity, electrical stimulation (ES) and osteoinductive activity is developed by in situ doping of MXene 2D nanomaterials with conductive functionality and ß-TCP particles into a Poly(lactic acid-carbonate (PDT) composite nano-absorbable membrane (P/T/MXene) via electrostatic spinning technique. The composite membrane has good feasibility due to its temperature sensitivity, elastic memory capacity, coordinated degradation profile and easy preparation process. In vitro experiments showed the P/T/MXene membrane effectively promoted the recruitment and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) under ES and enhanced the angiogenic capacity of endothelial cells, which synergistically promoted bone regeneration through neovascularization. In addition, an in vivo rat model of cranial bone defects further confirmed the bone regeneration efficacy of the P/T/MXene membrane. In conclusion, the developed P/T/MXene membrane can effectively promote bone regeneration through their synergistic multifunctional effects, suggesting the membranes have great potential for guiding tissue regeneration and providing guidance for the biomaterials design.
RESUMO
DNA nanostructures with diverse biological functions have made significant advancements in biomedical applications. However, a universal strategy for the efficient production of DNA nanostructures is still lacking. In this work, a facile and mild method is presented for self-assembling polyethylenimine-modified carbon dots (PEI-CDs) and DNA into nanospheres called CANs at room temperature. This makes CANs universally applicable to multiple biological applications involving various types of DNA. Due to the ultra-small size and strong cationic charge of PEI-CDs, CANs exhibit a dense structure with high loading capacity for encapsulated DNA while providing excellent stability by protecting DNA from enzymatic hydrolysis. Additionally, Mg2+ is incorporated into CANs to form Mg@CANs which enriches the performance of CANs and enables subsequent biological imaging applications by providing exogenous Mg2+. Especially, a DNAzyme logic gate system that contains AND and OR Mg@CANs is constructed and successfully delivered to tumor cells in vitro and in vivo. They can be specifically activated by endogenic human apurinic/apyrimidinic endonuclease 1 and recognize the expression levels of miRNA-21 and miRNA-155 at tumor sites by logic biocomputing. A versatile pattern for delivery of diverse DNA and flexible logic circuits for multiple miRNAs imaging are developed.
Assuntos
Carbono , DNA , MicroRNAs , Nanosferas , Polietilenoimina , Pontos Quânticos , Carbono/química , Humanos , Nanosferas/química , DNA/química , Pontos Quânticos/química , Polietilenoimina/química , DNA Catalítico/química , Animais , Neoplasias/diagnóstico por imagem , Lógica , Linhagem Celular TumoralRESUMO
OBJECTIVE: To quantitatively analyze the morphological characteristics of osteophytes in DISH and syndesmophytes in AS, and summarize different ossification patterns to help identify the two diseases. Associated factors for new bone formation would be investigated. METHODS: Fifty patients with DISH and 50 age-, sex-, CT examination site- matched patients with AS were enrolled. Radiographic and clinical data were reviewed. Osteophytes (syndesmophytes) in front of each vertebral body and the corresponding intervertebral disc space were defined as vertebral osteophytes unit (VOU). The volume, angle and location (contralateral, ipsilateral, bilateral) of osteophytes in each VOU were measured and compared between DISH and AS groups. RESULTS: In each VOU, the volume and angle of osteophytes in DISH were significantly larger. The best osteophytes volume and angle cutoff value in predicting DISH was 0.59 cm3 and 40.15°. Contralateral, bilateral, ipsilateral osteophytes were recorded in 59.32%, 36.38%, 4.3% of assessed VOUs in patients with DISH and 64.78%, 29.31%, 5.91% in AS (p<0.001), respectively. As to ipsilateral osteophytes, the volume was inversely correlated with the center of the vertebral body to the center of the descending aorta (DISH: r = -0.45, p= 0.01; AS: r = -0.83, p<0.001). Advanced age, disease duration, smoking and overweight contribute to the progression of osteophytes and syndesmophytes. CONCLUSION: Morphological features of osteophytes are helpful to distinguish DISH with AS. Aortic pulsations inhibit or hinder new bone formation in both DISH and AS. Maintaining normal BMI could postpone osteophytes formation.
RESUMO
Denitrification plays a critical role in soil nitrogen (N) cycling, affecting N availability in agroecosystems. However, the challenges in direct measurement of denitrification products (NO, N2 O, and N2 ) hinder our understanding of denitrification N losses patterns across the spatial scale. To address this gap, we constructed a data-model fusion method to map the county-scale denitrification N losses from China's rice fields over the past decade. The estimated denitrification N losses as a percentage of N application from 2009 to 2018 were 11.8 ± 4.0% for single rice, 12.4 ± 3.7% for early rice, and 11.6 ± 3.1% for late rice. The model results showed that the spatial heterogeneity of denitrification N losses is primarily driven by edaphic and climatic factors rather than by management practices. In particular, diffusion and production rates emerged as key contributors to the variation of denitrification N losses. These findings humanize a 38.9 ± 4.8 kg N ha-1 N loss by denitrification and challenge the common hypothesis that substrate availability drives the pattern of N losses by denitrification in rice fields.
Assuntos
Oryza , Desnitrificação , Projetos de Pesquisa , Nitrogênio , ChinaRESUMO
KEY MESSAGE: A total of 389 and 344 QTLs were identified by GWAS and QTL mapping explaining accumulatively 32.2-65.0% and 23.7-63.4% of phenotypic variation for 14 shoot-borne root traits using more than 1300 individuals across multiple field trails. Efficient nutrient and water acquisition from soils depends on the root system architecture (RSA). However, the genetic determinants underlying RSA in maize remain largely unexplored. In this study, we conducted a comprehensive genetic analysis for 14 shoot-borne root traits using 513 inbred lines and 800 individuals from four recombinant inbred line (RIL) populations at the mature stage across multiple field trails. Our analysis revealed substantial phenotypic variation for these 14 root traits, with a total of 389 and 344 QTLs identified through genome-wide association analysis (GWAS) and linkage analysis, respectively. These QTLs collectively explained 32.2-65.0% and 23.7-63.4% of the trait variation within each population. Several a priori candidate genes involved in auxin and cytokinin signaling pathways, such as IAA26, ARF2, LBD37 and CKX3, were found to co-localize with these loci. In addition, a total of 69 transcription factors (TFs) from 27 TF families (MYB, NAC, bZIP, bHLH and WRKY) were found for shoot-borne root traits. A total of 19 genes including PIN3, LBD15, IAA32, IAA38 and ARR12 and 19 GWAS signals were overlapped with selective sweeps. Further, significant additive effects were found for root traits, and pyramiding the favorable alleles could enhance maize root development. These findings could contribute to understand the genetic basis of root development and evolution, and provided an important genetic resource for the genetic improvement of root traits in maize.
Assuntos
Estudo de Associação Genômica Ampla , Zea mays , Humanos , Zea mays/genética , Genômica , Mapeamento Cromossômico , AlelosRESUMO
The theory of heat conduction paths has been widely recognized and widely studied in the research about the thermal conductivity of thermal conductive polymer composites at present. Encapsulating polymer pellets with thermally conductive fillers and processing them into thermally conductive polymer composites is a simple and effective method for constructing heat conduction paths. It is meaningful to investigate the related heat conduction mechanism of this method. Otherwise, this approach can significantly preserve the performance of the polymer substrate, making it highly valuable for practical material applications. In this work, polyethylene-octene elastomer (POE) pellets were encapsulated with thermal conductive fillers by physical absorption. Subsequently, the composite films containing heat conduction paths were fabricated using the encapsulated POE pellets through a heating press. Alumina (Al2O3), boron nitride (BN), and alumina/boron nitride hybrid (Al2O3/BN) fillers were used to prepare Al2O3@POE, BN@POE, and BN/Al2O3@POE composite films to investigate the influence of filler shapes on heat conduction path construction. The influence of the constitute and density of heat conduction paths on the thermal conductivity of composite films was analyzed by infrared thermal imaging, finite element analysis, and thermal resistance theory in detail. Owing to the reserved good adhesion and flexibility of the POE substrate, the composite films could be directly used as thermal interface materials for chip cooling, which presented a good heat dissipation effect. Furthermore, a series of integrated composite materials were prepared by the combination of encapsulated pellets with various functional films (copper foil, aluminum foil, and graphite sheet) through a one-pot heating press, exhibiting a good electromagnetic shielding effect. The performance of the composites and the corresponding preparation method demonstrate the strong significance of this research for practical applications.
RESUMO
OBJECTIVE: The efficacy of single-incision plus one-port laparoscopic surgery (SILS + 1) versus conventional laparoscopic surgery (CLS) for colorectal cancer treatment remains unclear. This study compares the short-term and long-term outcomes of SILS + 1 and CLS using a high-quality systematic review and meta-analysis. METHOD: Literature search followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, drawing from PubMed, Embase, Web of Science, and the Cochrane Library until December 10, 2023. Statistical analysis was conducted using RevMan and Stata. RESULT: The review and meta-analysis included seven studies with 1740 colorectal cancer patients. Compared to CLS, SILS + 1 showed significant improvements in operation time (WMD = - 18.33, P < 0.00001), blood loss (WMD = - 21.31, P < 0.00001), incision length (WMD = - 2.07, P < 0.00001), time to first defecation (WMD = - 14.91, P = 0.009), time to oral intake (WMD = - 11.46, P = 0.04), and time to ambulation (WMD = - 11.52, P = 0.01). There were no significant differences in lymph node harvest, resection margins, complications, anastomotic leakage, hospital stay, disease-free survival, overall survival, and postoperative recurrence. CONCLUSIONS: Compared to CLS, SILS + 1 demonstrates superiority in shortening the surgical incision and promoting postoperative recovery. SILS + 1 can provide a safe and feasible alternative to CLS.
Assuntos
Neoplasias Colorretais , Laparoscopia , Humanos , Neoplasias Colorretais/cirurgia , Resultado do Tratamento , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Tempo de Internação , Feminino , Masculino , Recidiva Local de Neoplasia , Pessoa de Meia-IdadeRESUMO
Acute myelogenous leukemia (AML) is the most common form of acute leukemia in adults. PDE1 (Phosphodiesterase 1) is a subfamily of the PDE super-enzyme families that can hydrolyze the second messengers cAMP and cGMP simultaneously. Previous research has shown that suppressing the gene expression of PDE1 can trigger apoptosis of human leukemia cells. However, no selective PDE1 inhibitors have been used to explore whether PDE1 is a potential target for treating AML. Based on our previously reported PDE9/PDE1 dual inhibitor 11a, a series of novel pyrazolopyrimidinone derivatives were designed in this study. The lead compound 6c showed an IC50 of 7.5 nM against PDE1, excellent selectivity over other PDEs and good metabolic stability. In AML cells, compound 6c significantly inhibited the proliferation and induced apoptosis. Further experiments indicated that the apoptosis induced by 6c was through a mitochondria-dependent pathway by decreasing the ratio of Bcl-2/Bax and increasing the cleavage of caspase-3, 7, 9, and PARP. All these results suggested that PDE1 might be a novel target for AML.
Assuntos
Leucemia Mieloide Aguda , Inibidores de Fosfodiesterase , Pirazóis , Pirimidinonas , Adulto , Humanos , Inibidores de Fosfodiesterase/farmacologia , Diester Fosfórico Hidrolases/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , GMP Cíclico/metabolismoRESUMO
Hypertension is a prominent contributor to vascular injury. Deubiquinatase has been implicated in the regulation of hypertension-induced vascular injury. In the present study we investigated the specific role of deubiquinatase YOD1 in hypertension-induced vascular injury. Vascular endothelial endothelial-mesenchymal transition (EndMT) was induced in male WT and YOD1-/- mice by administration of Ang II (1 µg/kg per minute) via osmotic pump for four weeks. We showed a significantly increased expression of YOD1 in mouse vascular endothelial cells upon Ang II stimulation. Knockout of YOD1 resulted in a notable reduction in EndMT in vascular endothelial cells of Ang II-treated mouse; a similar result was observed in Ang II-treated human umbilical vein endothelial cells (HUVECs). We then conducted LC-MS/MS and co-immunoprecipitation (Co-IP) analyses to verify the binding between YOD1 and EndMT-related proteins, and found that YOD1 directly bound to ß-catenin in HUVECs via its ovarian tumor-associated protease (OTU) domain, and histidine at 262 performing deubiquitination to maintain ß-catenin protein stability by removing the K48 ubiquitin chain from ß-catenin and preventing its proteasome degradation, thereby promoting EndMT of vascular endothelial cells. Oral administration of ß-catenin inhibitor MSAB (20 mg/kg, every other day for four weeks) eliminated the protective effect of YOD1 deletion on vascular endothelial injury. In conclusion, we demonstrate a new YOD1-ß-catenin axis in regulating Ang II-induced vascular endothelial injury and reveal YOD1 as a deubiquitinating enzyme for ß-catenin, suggesting that targeting YOD1 holds promise as a potential therapeutic strategy for treating ß-catenin-mediated vascular diseases.
Assuntos
Angiotensina II , Células Endoteliais da Veia Umbilical Humana , Camundongos Endogâmicos C57BL , Camundongos Knockout , beta Catenina , Animais , beta Catenina/metabolismo , Humanos , Angiotensina II/farmacologia , Angiotensina II/metabolismo , Masculino , Camundongos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Endotélio-MesênquimaRESUMO
BACKGROUND: Oculocutaneous albinism (OCA) is a group of autosomal recessive hereditary disorders that affect melanin biosynthesis, resulting in abnormalities in hair, skin, and eyes. Retinopathy of prematurity (ROP) is a proliferative retinopathy mainly observed in premature infants with low birth weight and early gestational age, but it can also affect full-term infants or children with normal weight, particularly in developing countries. The coexistence of ROP and OCA is rare. There is limited documentation regarding treatment approaches, with few studies reporting positive outcomes with laser treatment due to the absence of melanin pigment. This study discusses the treatment challenges in a female infant diagnosed with ROP and OCA, and underscores the importance of genetic analysis in guiding therapeutic decisions for this rare comorbid condition. CASE PRESENTATION: The study presents a case of ROP occurring concurrently with OCA. Genetic testing revealed two variants, c.727C > T (p.R243C) and c.1832 T > C (p.L611P), in the OCA2 gene, inherited from the patient's mother and father, respectively. The identified mutations were consistent with a diagnosis of OCA2, classified as a subtype of OCA. The patient initially received intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection, followed by laser photocoagulation therapy for a recurrent event. A favorable outcome was observed during the 2-month follow-up period. CONCLUSIONS: The co-occurrence of ROP and OCA is a rare phenomenon, and this is the first recorded case in the Chinese population. The current case supports the use of laser as the primary treatment modality for ROP in OCA2 patients with partial pigmentation impairment. Furthermore, genetic analysis can aid in predicting the effectiveness of laser photocoagulation in this patient population.
Assuntos
Albinismo Oculocutâneo , Retinopatia da Prematuridade , Humanos , Feminino , Albinismo Oculocutâneo/genética , Albinismo Oculocutâneo/complicações , Albinismo Oculocutâneo/terapia , Retinopatia da Prematuridade/genética , Retinopatia da Prematuridade/terapia , Retinopatia da Prematuridade/complicações , Recém-Nascido , Proteínas de Membrana Transportadoras/genética , Mutação , Inibidores da Angiogênese/uso terapêutico , Fotocoagulação a Laser , Bevacizumab/uso terapêuticoRESUMO
Currently, platinum agents remain the mainstay of chemotherapy for ovarian cancer (OC). However, cisplatin (DDP) resistance is a major reason for chemotherapy failure. Thus, it is extremely important to elucidate the mechanism of resistance to DDP. Here, we establish two DDP-resistant ovarian cancer cell lines and find that caseinolytic protease P (CLPP) level is significantly downregulated in DDP-resistant cell lines compared to wild-type ovarian cancer cell lines (SK-OV-3 and OVcar3). Next, we investigate the functions of CLPP in DDP-resistant and wild-type ovarian cancer cells using various assays, including cell counting kit-8 assay, western blot analysis, immunofluorescence staining, and detection of reactive oxygen species (ROS) and apoptosis. Our results show that CLPP knockdown significantly increases the half maximal inhibitory concentration (IC 50) and mitophagy of wild-type SK-OV-3 and OVcar3 cells, while CLPP overexpression reduces the IC 50 values and mitophagy of DDP-resistant SK-OV-3 and OVcar3 cells. Next, we perform database predictions and confirmation experiments, which show that heat shock protein family A member 8 (HSPA8) regulates CLPP protein stability. The dynamic effects of the HSPA8/CLPP axis in ovarian cancer cells are also examined. HSPA8 increases mitophagy and the IC 50 values of SK-OV-3 and OVcar3 cells but inhibits their ROS production and apoptosis. In addition, CLPP partly reverses the effects induced by HSPA8 in SK-OV-3 and OVcar3 cells. In conclusion, CLPP increases DDP resistance in ovarian cancer by inhibiting mitophagy and promoting cellular stress. Meanwhile, HSPA8 promotes the degradation of CLPP protein by regulating its stability.
Assuntos
Antineoplásicos , Neoplasias Ovarianas , Feminino , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Autofagia , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Endopeptidase Clp , Proteínas de Choque Térmico HSC70/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Paraquat (PQ) poisoning leads to irreversible fibrosis in the lungs with high mortality and no known antidote. In this study, we investigated the effect of the SET and MYND domain containing 2 (SMYD2) on PQ-induced pulmonary fibrosis (PF) and its potential mechanisms. We established an in vivo PQ-induced PF mouse model by intraperitoneal injection of PQ (20 mg/kg) and in vitro PQ (25 µM)-injured MLE-12 cell model. On the 15th day of administration, tissue injury, inflammation, and fibrosis in mice were evaluated using various methods including routine blood counts, blood biochemistry, blood gas analysis, western blotting, H&E staining, ELISA, Masson staining, and immunofluorescence. The findings indicated that AZ505 administration mitigated tissue damage, inflammation, and collagen deposition in PQ-poisoned mice. Mechanistically, both in vivo and in vitro experiments revealed that AZ505 treatment suppressed the PQ-induced epithelial-mesenchymal transition (EMT) process by downregulating GLI pathogenesis related 2 (GLIPR2) and ERK/p38 pathway. Further investigations demonstrated that SMYD2 inhibition decreased GLIPR2 methylation and facilitated GLIPR2 ubiquitination, leading to GLIPR2 destabilization in PQ-exposed MLE-12 cells. Moreover, rescue experiments conducted in vitro demonstrated that GLIPR2 overexpression eliminated the inhibitory effect of AZ505 on the ERK/p38 pathway and EMT. Our results reveal that the SMYD2 inhibitor AZ505 may act as a novel therapeutic candidate to suppress the EMT process by modulating the GLIPR2/ERK/p38 axis in PQ-induced PF.
Assuntos
Transição Epitelial-Mesenquimal , Paraquat , Fibrose Pulmonar , Animais , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/patologia , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Camundongos , Paraquat/toxicidade , Masculino , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Linhagem Celular , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/antagonistas & inibidores , Histona-Lisina N-Metiltransferase/genéticaRESUMO
BACKGROUND: Within the tumor microenvironment, survival pressures are prevalent with potent drivers of tumor progression, angiogenesis, and therapeutic resistance. N6-methyladenosine (m6A) methylation has been recognized as a critical post-transcriptional mechanism regulating various aspects of mRNA metabolism. Understanding the intricate interplay between survival pressures and m6A modification provides new insights into the molecular mechanisms underlying hepatocellular carcinoma (HCC) progression and highlights the potential for targeting the survival pressures-m6A axis in HCC diagnosis and treatment. DATA SOURCES: A literature search was conducted in PubMed, MEDLINE, and Web of Science for relevant articles published up to April 2024. The keywords used for the search included hepatocellular carcinoma, cellular survival, survival pressure, N6-methyladenosine, tumor microenvironment, stress response, and hypoxia. RESULTS: This review delves into the multifaceted roles of survival pressures and m6A RNA methylation in HCC, highlighting how survival pressures modulate the m6A landscape, the impact of m6A modification on survival pressure-responsive gene expression, and the consequent effects on HCC cell survival, proliferation, metastasis, and resistance to treatment. Furthermore, we explored the therapeutic potential of targeting this crosstalk, proposing strategies that leverage the understanding of survival pressures and m6A RNA methylation mechanisms to develop novel, and more effective treatments for HCC. CONCLUSIONS: The interplay between survival pressures and m6A RNA methylation emerges as a complex regulatory network that influences HCC pathogenesis and progression.
RESUMO
PURPOSE: Gasless robot-assisted transaxillary hemithyroidectomy (RATH) is regarded as an alternative surgical option for thyroid operations. However, the associated steep learning curve is a clinical concern. This study evaluated the learning curve of RATH for surgeons without experience of endoscopic surgery and the early surgical outcomes of RATH. METHODS: We conducted a retrospective study of patients who underwent gasless RATH and conventional hemithyroidectomy (CH) at Sun Yat-sen University Cancer Center, Guangzhou, China, from June 2021 to August 2022. The learning curve and early surgical outcomes of gasless RATH were evaluated. And the early surgical outcomes of gasless RATH were compared to CH. RESULTS: In total, 105 patients who underwent gasless RATH and 104 patients who underwent CH were matched and assessed. The cumulative sum techniques (CUSUM) analysis showed that the peak point of gasless RATH operative time occurred at the 31st case. No clear single peak was identified in the CUSUM plot for drainage amount and blood loss. No significant difference in perioperative complications was observed between these two groups. Moreover, the number of postoperative patients who got sense of thyroid area traction were fewer in the gasless RATH group (n = 11, 10.5%) than in the CH group (n = 32, 30.8%). CONCLUSION: Gasless RATH can be considered as an alternative approach to the conventional open procedure, as it is an easy remote access technique, with shorter learning curves and certain advantage such as less sense of thyroid area traction.
Assuntos
Robótica , Neoplasias da Glândula Tireoide , Humanos , Curva de Aprendizado , Neoplasias da Glândula Tireoide/cirurgia , Robótica/métodos , Estudos Retrospectivos , Tireoidectomia/métodos , Complicações Pós-Operatórias/etiologiaRESUMO
The detection of instability inception is favorable to avoid compressor instability. In this paper, a multiscale entropy-based feature extraction is developed for the detection of the instability inception in axial compressors. Nonlinear and statistical features of the short-time instability inception are extracted by generally combining multiscale entropy and statistical features. First, nonlinear features are extracted by refined composite multiscale entropy to avoid the inaccurate estimation or undefined entropy of multiscale entropy for short time series. Second, the time-domain-based statistical features are chosen to capture more information on instability inception, and the dominant statistical features are determined by random forests implemented with the mean decrease accuracy algorithm at each time scale. The obtained refined composite dominant statistical features are regarded as weighting factors and integrated with the refined composite multiscale entropy to generate a combined feature. Finally, numerical simulation results on two synthetic noise datasets and a compressor instability model dataset are presented to demonstrate the effectiveness, efficiency, and robustness of the combined features under different conditions.
RESUMO
Small organic photothermal agents (PTAs) with absorption bands located in the second near-infrared (NIR-II, 1000-1700â nm) window are highly desirable for effectively combating deep-seated tumors. However, the rarely reported NIR-II absorbing PTAs still suffer from a low molar extinction coefficient (MEC, ϵ), inadequate chemostability and photostability, as well as the high light power density required during the therapeutic process. Herein, we developed a series of boron difluoride bridged azafulvene dimer acceptor-integrated small organic PTAs. The B-N coordination bonds in the π-conjugated azafulvene dimer backbone endow it the strong electron-withdrawing ability, facilitating the vigorous donor-acceptor-donor (D-A-D) structure PTAs with NIR-II absorption. Notably, the PTA namely OTTBF shows high MEC (7.21×104â M-1 cm-1), ultrahigh chemo- and photo-stability. After encapsulated into water-dispersible nanoparticles, OTTBF NPs can achieve remarkable photothermal conversion effect under 1064â nm irradiation with a light density as low as 0.7â W cm-2, which is the lowest reported NIR-II light power used in PTT process as we know. Furthermore, OTTBF NPs have been successfully applied for in vitro and in vivo deep-seated cancer treatments under 1064â nm laser. This study provides an insight into the future exploration of versatile D-A-D structured NIR-II absorption organic PTAs for biomedical applications.
Assuntos
Compostos de Boro , Lasers , Terapia Fototérmica , Compostos de Boro/química , Camundongos , Animais , Humanos , Antineoplásicos/química , Antineoplásicos/farmacologia , Dimerização , Estrutura Molecular , Linhagem Celular Tumoral , Compostos Aza/química , Ensaios de Seleção de Medicamentos Antitumorais , Sobrevivência Celular/efeitos dos fármacos , Raios Infravermelhos , Proliferação de Células/efeitos dos fármacosRESUMO
Understanding the properties of the precursor can provide deeper insight into the crystallization and nucleation mechanisms of perovskites, which is vital for the solution-process device performance. Herein, we conducted a detailed investigation into the photophysics properties of CsPbBr3 precursors in a broad concentration and various solvents. The precursor transformed from the solution state into the colloidal state and exhibited aggregation-induced emission character as the concentration increased. The aggregative luminescence from the precursors originates from the polybromide plumbous that is formed through the coordination of solvent molecules to the lead metal center. Two adducts with monodentate (PbBr2 â solvent) and bidentate (PbBr2 â 2solvent) ligands can be obtained, accompanied by emission with photoluminescence at 610 and 565â nm, respectively. Furthermore, the aggregative luminescence intensity and color could be regulated by changing the solvent and precursor ratio. Besides, we discussed the difference between the molecular aggregate in the organic system and the ionic aggregate in the inorganic system: the ionic aggregate is composed of solvated ions rather than individual molecules as in organic systems, which could possess properties that ions do not have. The fluorescence that is sensitive to Pb2+ coordination reported here could be applied to screen perovskite additives and judge the precursor aging.