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1.
J Environ Manage ; 360: 121104, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38733845

RESUMO

Excess nitrogen (N) discharged into streams and rivers degrades freshwater quality and threatens ecosystems worldwide. Land use patterns may influence riverine N export, yet the effect of location on N export and removal is not fully understood. We proposed a hybrid model to analyze N export and removal within the watersheds. The proposed model is satisfied for the riverine N modelling. The KGE and R2 are 0.75 and 0.72 in the calibration period which are 0.76 and 0.61 in the validation period. Human-impacted land use may modify the N yield in the watershed, and the net N export from built-up to the in-stream system was highest in the urbanized sub-watersheds (0.81), followed by the agricultural sub-watersheds (0.88), and forested sub-watersheds (0.96). Agricultural activities make a large contribution to the N exports in the watersheds, and the mean N input from the agricultural land use to in-stream were 2069-4353 kg km-2 yr-1. Besides, the excess inputs of N by overapplication of fertilizer and manure during the agricultural activities may increase legacy N in soil and groundwater. Biological processes for the riverine N removal may be controlled by the available substrate in the freshwater system, and temperature sensitivity of denitrification is highest in the flood seasons, especially for the human-impacted sub-watersheds. The riverine biological processes may be limited by other competitions. Our model results provide evidence that quantity and location of specific land use may control biogeochemistry within watersheds. We demonstrate the need to understand nutrient export and removal within watersheds by improving the representation of spatial patterns in existing watershed models, and we consider this study to be a new effort for the spatially explicit modeling to support land-use based N management in watersheds.

2.
Materials (Basel) ; 17(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38730807

RESUMO

CeO2 is widely used in the field of chemical-mechanical polishing for integrated circuits. Morphology, particle size, crystallinity, and Ce3+ concentration are crucial factors that affect polishing performance. In this study, we successfully synthesized two novel triangular CeO2 abrasives with similar particle sizes (600 nm) but different morphologies and Ce3+ concentrations using a microwave-assisted hydrothermal method with high-concentration raw materials, and no surfactants or template agents were added. It is generally believed that CeO2 with a higher Ce3+ concentration leads to better polishing performance. However, the results of polishing indicate that CeO2 synthesized at 200 °C, despite its lower Ce3+ concentration, demonstrates outstanding polishing performance, achieving a polishing rate of 324 nm/min, and the Sa of Si wafers decreased by 3.6% after polishing. This suggests that, under similar particle size conditions, the morphology of CeO2 plays a dominant role in the mechanical effects during the polishing process. Additionally, compared to commercial polishing slurries, the synthesized samples demonstrated better polishing performance. This indicates that, in CMP, the pursuit of smaller spherical abrasives may not be necessary. Instead, the appropriate shape and particle size can better balance the material removal rate and surface roughness.

3.
Adv Mater ; : e2312343, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691579

RESUMO

Seawater batteries that directly utilize natural seawater as electrolytes are ideal sustainable aqueous devices with high safety, exceedingly low cost, and environmental friendliness. However, the present seawater batteries are either primary batteries or rechargeable half-seawater/half-nonaqueous batteries because of the lack of suitable anode working in seawater. Here, a unique lattice engineering to unlock the electrochemically inert anatase TiO2 anode to be highly active for the reversible uptake of multiple cations (Na+, Mg2+, and Ca2+) in aqueous electrolytes is demonstrated. Density functional theory calculations further reveal the origin of the unprecedented charge storage behaviors, which can be attributed to the significant reduction of the cations diffusion barrier within the lattice, i.e., from 1.5 to 0.4 eV. As a result, the capacities of anatase TiO2 with 2.4% lattice expansion are ≈100 times higher than the routine one in natural seawater, and ≈200 times higher in aqueous Na+ electrolyte. The finding will significantly advance aqueous seawater energy storage devices closer to practical applications.

4.
Carbohydr Polym ; 337: 122085, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38710579

RESUMO

Microfibrillated cellulose (MFC) is a bio-material produced by disintegrating cellulose fibres into fibrillar components. MFC could offer a sustainable solution to packaging needs since it can form an excellent barrier to oxygen. However, a comprehensive understanding of how MFC characteristics impact barrier properties of MFC films or coatings is required. This article critically reviews how the extent of separation of fibres into fibrils-and any resulting changes to the crystallinity and degree of polymerisation of cellulose-influences gas barrier properties of MFC films or coatings. Findings from publications investigating the barrier performance of MFC prepared through different processes intending to increase the effectiveness of fibrillation are evaluated and compared. The effects of processing conditions or chemical pre-treatments on barrier properties of MFC films or coatings are then discussed. A comparison of reported results showed that morphology and size polydispersity of the cellulose strongly influence the barrier properties of MFC. However, changing the MFC production process to decrease fibril diameter and polydispersity can result in changes to cellulose crystallinity; reduction in fibril length; introduction of bulky functional groups; or increased fibril surface charge: all of which could have a negative impact on the barrier properties of the final films or coatings.

5.
Nanoscale Adv ; 6(8): 2002-2012, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38633054

RESUMO

Copper (Cu) has a soft-plastic nature, which makes it susceptible to damages from scratching or abrasive machining, such as lapping and polishing. It is a challenge to control these damages as the damage mechanism is elusive. Nonetheless, controlling damages is essential, especially on the atomic surfaces of Cu. To interpret the damage mechanism, in situ transmission electron microscopy (TEM) nanoindentation was performed using a cube-corner indenter with a radius of 57 nm at a loading speed of 5 nm s-1. Experimental results showed that damages originate from dislocations, evolve to stack faults, and then form broken crystallites. When the indentation depth was 45 nm at a load of 20 µN, damages comprised dislocations and stacking faults. After increasing the depth to 67 nm and load to 30 µN, the formation of broken crystallites initiated; and the critical depth was 67 nm. To validate the damage mechanism, fixed-abrasive lapping, mechanical polishing, and chemical mechanical polishing (CMP) were conducted. Firstly, a novel green CMP slurry containing silica, hydrogen peroxide, and aspartic acid was developed. After CMP, a surface roughness Ra of 0.2 nm was achieved with a scanning area of 50 µm × 50 µm; and the thickness of the damaged layer was 3.1 nm, which included a few micro-stacking faults. Lapping and mechanical polishing were carried out using a silicon carbide plate and cerium slurry, with surface roughness Ra values of 16.42 and 1.74 nm, respectively. The damaged layer of the former with a thickness of 300 nm comprised broken crystallites, dislocations, and stacking faults and that of the latter with a thickness of 33 nm involved several stacking faults. This verifies that the damage mechanism derived from in situ TEM nanoindentation is in agreement with lapping and polishing. These outcomes propose new insights into understanding the origin of damages and controlling them, as well as obtaining atomic surfaces using a novel green CMP technique for soft-plastic metals.

6.
Front Pharmacol ; 15: 1375112, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38666025

RESUMO

IDH wild-type glioblastoma (GBM) intrinsic subtypes have been linked to different molecular landscapes and outcomes. Accurate prediction of molecular subtypes of GBM is very important to guide clinical diagnosis and treatment. Leveraging machine learning technology to improve the subtype classification was considered a robust strategy. Several single machine learning models have been developed to predict survival or stratify patients. An ensemble learning strategy combines several basic learners to boost model performance. However, it still lacked a robust stacking ensemble learning model with high accuracy in clinical practice. Here, we developed a novel integrative stacking ensemble model framework (ecGBMsub) for improving IDH wild-type GBM molecular subtype classification. In the framework, nine single models with the best hyperparameters were fitted based on extrachromosomal circular DNA (eccDNA) molecular profiling. Then, the top five optimal single models were selected as base models. By randomly combining the five optimal base models, 26 different combinations were finally generated. Nine different meta-models with the best hyperparameters were fitted based on the prediction results of 26 different combinations, resulting in 234 different stacked ensemble models. All models in ecGBMsub were comprehensively evaluated and compared. Finally, the stacking ensemble model named "XGBoost.Enet-stacking-Enet" was chosen as the optimal model in the ecGBMsub framework. A user-friendly web tool was developed to facilitate accessibility to the XGBoost.Enet-stacking-Enet models (https://lizesheng20190820.shinyapps.io/ecGBMsub/).

7.
Materials (Basel) ; 17(3)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38591422

RESUMO

It is a challenge to polish the interior surface of a small bent pipe with complex structures and sizes less than 0.5 mm. This is because of the fact that traditional polishing methods could destroy, block, or break the small complex structures. For a small bent pipe made of aluminum alloy produced using additive manufacturing, the defects, such as adhered powders and spatters, are easy to jam the pipe without polishing, possibly resulting in catastrophic failure for aerospace applications. To overcome this challenge, a novel water jet polisher was developed using soft polymethyl methacrylate (PMMA) abrasives. After polishing a specific area, the adhered powders on the interior surface were reduced from over 140 to 2, 3, and 6 by the soft abrasives with mesh sizes of 200, 400, and 600, respectively. The surface roughness Sa was decreased from 3.41 to 0.92 µm after polishing using PMMA abrasives with a mesh size of 200. In comparison, silica abrasives were also employed to polish the small bent pipes, leading to the bent part of pipes breaking. However, this kind of failure was absent when using soft abrasives. Computational fluid dynamics calculations elucidate that a peak erosion rate of silica abrasives for a bent pipe with a turn angle of 30° is 2.18 kg/(m2·s), which is 17 times that of soft abrasives. This is why the small bent pipe was broken using silica abrasives, whereas it remained intact when polished with soft abrasives. In addition, water jet polishing has a lower erosion rate, a relatively smooth erosion curve, and less erosion energy, leaving the bent parts intact. The developed soft abrasive water jet polisher and the findings of this study suggest new possibilities for cleaning the adhered powders and spatters and polishing the interior surface of small bent pipes with complex structures.

8.
Cell ; 187(10): 2375-2392.e33, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38653238

RESUMO

Lysine lactylation is a post-translational modification that links cellular metabolism to protein function. Here, we find that AARS1 functions as a lactate sensor that mediates global lysine lacylation in tumor cells. AARS1 binds to lactate and catalyzes the formation of lactate-AMP, followed by transfer of lactate to the lysince acceptor residue. Proteomics studies reveal a large number of AARS1 targets, including p53 where lysine 120 and lysine 139 in the DNA binding domain are lactylated. Generation and utilization of p53 variants carrying constitutively lactylated lysine residues revealed that AARS1 lactylation of p53 hinders its liquid-liquid phase separation, DNA binding, and transcriptional activation. AARS1 expression and p53 lacylation correlate with poor prognosis among cancer patients carrying wild type p53. ß-alanine disrupts lactate binding to AARS1, reduces p53 lacylation, and mitigates tumorigenesis in animal models. We propose that AARS1 contributes to tumorigenesis by coupling tumor cell metabolism to proteome alteration.


Assuntos
Carcinogênese , Ácido Láctico , Proteína Supressora de Tumor p53 , Humanos , Proteína Supressora de Tumor p53/metabolismo , Animais , Carcinogênese/metabolismo , Carcinogênese/genética , Camundongos , Ácido Láctico/metabolismo , Linhagem Celular Tumoral , Processamento de Proteína Pós-Traducional , Lisina/metabolismo , Neoplasias/metabolismo , Neoplasias/genética , Feminino
9.
Artigo em Inglês | MEDLINE | ID: mdl-38648292

RESUMO

Given the escalating global crisis in feed protein availability, Jatropha curcas L. cake has attracted significant interest as a viable alternative protein source in animal feed. This experiment was conducted to investigate the effects of fermented Jatropha curcas L. cake (FJCC) as a protein feed in the diet of pigs. A total of 96 growing pigs with an average weight of 27.60 ± 1.59 kg were divided into three dietary groups with varying FJCC inclusion levels (0, 2.5, and 5%) for a 28 d trial. Results showed that the diet with 5% FJCC (FJCC5) demonstrated significant improvements in average daily gain (p = 0.009), feed-to-gain ratio (p = 0.036), nutrient digestibility, and intestinal morphology. Furthermore, the FJCC5 diet resulted in a decrease in pH values in different gut sections (jejunum p = 0.045, cecum p = 0.001, colon p = 0.012), and favorably altered the profile of short-chain fatty acids (SCFAs) with increased butyric acid content (p = 0.005) and total SCFAs (p = 0.019). Additionally, this diet notably decreased IL-6 levels in the jejunum (p = 0.008) and colon (=0.047), significantly reduced IL-1 levels in the hypothalamus (p < 0.001), and lowered IL-1, IL-6, and IL-10 levels in plasma (p < 0.05). Microbiota and metabolite profile analysis revealed an elevated abundance of beneficial microbes (p < 0.05) and key metabolites such as 4-aminobutyric acid (GABA) (p = 0.003) and serotonin (5-HT) (p = 0.022), linked to neuroactive ligand-receptor interaction. Moreover, FJCC5 significantly boosted circulating neurotransmitter levels of 5-HT (p = 0.006) and GABA (p = 0.002) in plasma and hypothalamus, with corresponding increases in precursor amino acids (p < 0.05). These findings suggest that FJCC, particularly at a 5% inclusion rate, can be an effective substitute for traditional protein sources like soybean meal, offering benefits beyond growth enhancement to gut health and potentially impacting the gut-brain axis. This research underscores FJCC's potential as a valuable component in sustainable animal nutrition strategies.

10.
CNS Neurosci Ther ; 30(4): e14709, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38605477

RESUMO

AIMS: Although radiotherapy is a core treatment modality for various human cancers, including glioblastoma multiforme (GBM), its clinical effects are often limited by radioresistance. The specific molecular mechanisms underlying radioresistance are largely unknown, and the reduction of radioresistance is an unresolved challenge in GBM research. METHODS: We analyzed and verified the expression of nuclear autoantigenic sperm protein (NASP) in gliomas and its relationship with patient prognosis. We also explored the function of NASP in GBM cell lines. We performed further mechanistic experiments to investigate the mechanisms by which NASP facilitates GBM progression and radioresistance. An intracranial mouse model was used to verify the effectiveness of combination therapy. RESULTS: NASP was highly expressed in gliomas, and its expression was negatively correlated with the prognosis of glioma. Functionally, NASP facilitated GBM cell proliferation, migration, invasion, and radioresistance. Mechanistically, NASP interacted directly with annexin A2 (ANXA2) and promoted its nuclear localization, which may have been mediated by phospho-annexin A2 (Tyr23). The NASP/ANXA2 axis was involved in DNA damage repair after radiotherapy, which explains the radioresistance of GBM cells that highly express NASP. NASP overexpression significantly activated the signal transducer and activator of transcription 3 (STAT3) signaling pathway. The combination of WP1066 (a STAT3 pathway inhibitor) and radiotherapy significantly inhibited GBM growth in vitro and in vivo. CONCLUSION: Our findings indicate that NASP may serve as a potential biomarker of GBM radioresistance and has important implications for improving clinical radiotherapy.


Assuntos
Anexina A2 , Neoplasias Encefálicas , Glioblastoma , Fator de Transcrição STAT3 , Animais , Humanos , Camundongos , Anexina A2/genética , Anexina A2/metabolismo , Anexina A2/uso terapêutico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/metabolismo , Proliferação de Células/genética , Glioblastoma/genética , Fator de Transcrição STAT3/genética , Linhagem Celular Tumoral
11.
ACS Nano ; 18(13): 9389-9402, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38507591

RESUMO

Degradation of cathode materials in lithium-ion batteries results in the presence of transition metal ions in the electrolyte, and these ions are known to play a major role in capacity fade and cell failure. Yet, while it is known that transition metal ions migrate from the metal oxide cathode and deposit on the graphite anode, their specific influence on anode reactions and structures, such as the solid electrolyte interphase (SEI), is still quite poorly understood due to the complexity in studying this interface in operational cells. In this work we combine operando electrochemical atomic force microscopy (EC-AFM), electrochemical quartz crystal microbalance (EQCM), and electrochemical impedance spectroscopy (EIS) measurements to probe the influence of a range of transition metal ions on the morphological, mechanical, chemical, and electrical properties of the SEI. By adding representative concentrations of Ni2+, Mn2+, and Co2+ ions into a commercially relevant battery electrolyte, the impacts of each on the formation and stability of the anode interface layer is revealed; all are shown to pose a threat to battery performance and stability. Mn2+, in particular, is shown to induce a thick, soft, and unstable SEI layer, which is known to cause severe degradation of batteries, while Co2+ and Ni2+ significantly impact interfacial conductivity. When transition metal ions are mixed, SEI degradation is amplified, suggesting a synergistic effect on the cell stability. Hence, by uncovering the roles these cathode degradation products play in operational batteries, we have provided a foundation upon which strategies to mitigate or eliminate these degradation products can be developed.

12.
Angew Chem Int Ed Engl ; : e202401987, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526053

RESUMO

The in-depth understanding of the composition-property-performance relationship of solid electrolyte interphase (SEI) is the basis of developing a reliable SEI to stablize the Zn anode-electrolyte interface, but it remains unclear in rechargeable aqueous zinc ion batteries. Herein, a well-designed electrolyte based on 2 M Zn(CF3SO3)2-0.2 M acrylamide-0.2 M ZnSO4 is proposed. A robust polymer (polyacrylamide)-inorganic (Zn4SO4(OH)6.xH2O) hybrid SEI is in situ constructed on Zn anodes through controllable polymerization of acrylamide and coprecipitation of SO4 2- with Zn2+ and OH-. For the first time, the underlying SEI composition-property-performance relationship is systematically investigated and correlated. The results showed that the polymer-inorganic hybrid SEI, which integrates the high modulus of the inorganic component with the high toughness of the polymer ingredient, can realize high reversibility and long-term interfacial stability, even under ultrahigh areal current density and capacity (30 mA cm-2~30 mAh cm-2). The resultant Zn||NH4V4O10 cell also exhibits excellent cycling stability. This work will provide a guidance for the rational design of SEI layers in rechargeable aqueous zinc ion batteries.

13.
Chem Biodivers ; : e202400210, 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38433548

RESUMO

Currently, natural products are one of the priceless options for finding novel chemical pharmaceutical entities. Ellipticine is a naturally occurring alkaloid isolated from the leaves of Ochrosia elliptica Labill. Ellipticine and its derivatives are characterized by multiple biological activities. The purpose of this review was to provide a critical and systematic assessment of ellipticine and its derivatives as bioactive molecules over the last 60 years. Publications focused mainly on the total synthesis of alkaloids of this type without any evaluation of bioactivity have been excluded. We have reviewed papers dealing with the synthesis, bioactivity evaluation and mechanism of action of ellipticine and its derivatives. It was found that ellipticine and its derivatives showed cytotoxicity, antimicrobial ability, and anti-inflammatory activity, among which cytotoxicity toward cancer cell lines was the most investigated aspect. The inhibition of DNA topoisomerase II was the most relevant mechanism for cytotoxicity. The PI3K/AKT pathway, p53 pathway, and MAPK pathway were also closely related to the antiproliferative ability of these compounds. In addition, the structure-activity relationship was deduced, and future prospects were outlined. We are confident that these findings will lay a scientific foundation for ellipticine-based drug development, especially for anticancer agents.

14.
J Phys Chem B ; 128(11): 2632-2639, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38467492

RESUMO

The cellular endocytosis of nanoparticles (NPs) is a fundamental biological process with significant potential in biomedical applications. However, a comprehensive understanding of the mechanistic aspects of endocytosis and the impact of particle properties on this process remains elusive. In this study, we investigated the membrane-wrapping behavior of soft NPs (SNPs) with varying rigidities using theoretical calculations. Our findings reveal that the membrane-wrapping process of SNPs involves a complex energy change including the possible existence of an energy barrier; moreover, it is found that the location and height of this barrier strongly depend on the mechanistic properties of the NPs and membranes. Additionally, by considering force balance in the membrane-wrapping process, we calculated the speed at which NP is internalized by the membrane, showing a nonmonotonic dependence on particle rigidity and/or wrapping degree. These phenomena can be attributed to competition between different energy components associated with NP-membrane binding, membrane tension, and deformations occurring during SNP-membrane interaction processes. Our results contribute to a deeper understanding of cellular-level endocytosis mechanisms and offer potential applications for soft NPs in biomedicine.


Assuntos
Nanopartículas , Membrana Celular/química , Nanopartículas/química , Membranas , Endocitose , Fenômenos Físicos
15.
Nat Commun ; 15(1): 2653, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38531845

RESUMO

Realization of higher-order multistates with mutual interstate switching in ferroelectric materials is a perpetual drive for high-density storage devices and beyond-Moore technologies. Here we demonstrate experimentally that antiferroelectric van der Waals CuInP2S6 films can be controllably stabilized into double, quadruple, and sextuple polarization states, and a system harboring polarization order of six is also reversibly tunable into order of four or two. Furthermore, for a given polarization order, mutual interstate switching can be achieved via moderate electric field modulation. First-principles studies of CuInP2S6 multilayers help to reveal that the double, quadruple, and sextuple states are attributable to the existence of respective single, double, and triple ferroelectric domains with antiferroelectric interdomain coupling and Cu ion migration. These findings offer appealing platforms for developing multistate ferroelectric devices, while the underlining mechanism is transformative to other non-volatile material systems.

16.
Ann Surg ; 279(4): 588-597, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38456278

RESUMO

OBJECTIVE: To compare the effect of low and standard pneumoperitoneal pressure (PP) on the occurrence of gas embolism during laparoscopic liver resection (LLR). BACKGROUND: LLR has an increased risk of gas embolism. Although animal studies have shown that low PP reduces the occurrence of gas embolism, clinical evidence is lacking. METHODS: This parallel, dual-arm, double-blind, randomized controlled trial included 141 patients undergoing elective LLR. Patients were randomized into standard ("S," 15 mm Hg; n = 70) or low ("L," 10 mm Hg; n = 71) PP groups. Severe gas embolism (≥ grade 3, based on the Schmandra microbubble method) was detected using transesophageal echocardiography and recorded as the primary outcome. Intraoperative vital signs and postoperative recovery profiles were also evaluated. RESULTS: Fewer severe gas embolism cases (n = 29, 40.8% vs n = 47, 67.1%, P = 0.003), fewer abrupt decreases in end-tidal carbon dioxide partial pressure, shorter severe gas embolism duration, less peripheral oxygen saturation reduction, and fewer increases in heart rate and lactate during gas embolization episodes was found in group L than in group S. Moreover, a higher arterial partial pressure of oxygen and peripheral oxygen saturation were observed, and fewer fluids and vasoactive drugs were administered in group L than in group S. In both groups, the distensibility index of the inferior vena cava negatively correlated with central venous pressure throughout LLR, and a comparable quality of recovery was observed. CONCLUSIONS: Low PP reduced the incidence and duration of severe gas embolism and achieved steadier hemodynamics and vital signs during LLR. Therefore, a low PP strategy can be considered a valuable choice for the future LLR.


Assuntos
Embolia Aérea , Laparoscopia , Animais , Humanos , Dióxido de Carbono/efeitos adversos , Embolia Aérea/etiologia , Embolia Aérea/prevenção & controle , Embolia Aérea/diagnóstico , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Fígado/cirurgia , Pneumoperitônio Artificial/efeitos adversos
17.
Int J Lab Hematol ; 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553845

RESUMO

INTRODUCTION: Acute lymphoblastic leukemia (ALL) is characterized by highly genetic heterogeneity, owing to recurrent fusion genes, gene mutations, intragenic deletion, and gene overexpression, which poses significant challenges in clinical detection. RNA sequencing (RNA-seq) is a powerful tool for detecting multiple genetic abnormalities, especially cryptic gene rearrangements, in a single test. METHODS: Sixty samples (B-ALL, n = 49; T-ALL, n = 9; mixed phenotype acute leukemia (MPAL), n = 2) and 20 controls were analyzed by targeted RNA-seq panel of 507 genes developed by our lab. Of these, 16 patients were simultaneously analyzed for gene mutations at the DNA level using a next-generation sequencing panel of 51 genes. Fusion genes, CRLF2 expression, and IKZF1 intragenic deletion were also detected by reverse transcription-polymerase chain reaction (RT-PCR). Karyotype analysis was performed using the R-banding and G-banding technique on bone marrow cells after 24 hours of culture. Partial fusion genes were analyzed using fluorescence in situ hybridization (FISH). RESULTS: Compared with the results of Karyotype analysis, FISH, and RT-PCR, the detection rate of fusion genes by targeted RNA-seq increased from 48.3% to 58.3%, and six unexpected fusion genes were discovered, along with one rare isoform of IKZF1 intragenic deletion (IK10). The DNA sequencing analysis of 16 ALL patients revealed that 96.2% (25/26) of gene mutations identified at the DNA level were also detectable at the RNA level, except for one mutation with a low variant allele fraction. The detection of CRLF2 overexpression exhibited complete concordance between RT-PCR and RNA-seq. CONCLUSION: The utilization of RNA-seq enables the identification of clinically significant genetic abnormalities that may go undetected through conventional detection methods. Its robust analytical performance might bring great application value for clinical diagnosis, prognosis, and therapy in ALL.

18.
Medicine (Baltimore) ; 103(10): e37062, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457552

RESUMO

BACKGROUND: Endoscopic treatment is increasingly used for refractory gastroesophageal reflux disease (rGERD). Unlike the mechanism of conventional surgical fundoplication, gastroesophageal junction ligation, anti-reflux mucosal intervention, and radiofrequency ablation have extremely similar anti-reflux mechanisms; hence, we collectively refer to them as endoscopic cardia peripheral tissue scar formation (ECSF). We conducted a systematic review and meta-analysis to assess the safety and efficacy of ECSF in treating rGERD. METHODS: We performed a comprehensive search of several databases, including PubMed, Embase, Medline, China Knowledge Network, and Wanfang, to ensure a systematic approach for data collection between January 2011 and July 2023. Forest plots were used to summarize and combine the GERD-health-related quality of life (HRQL), gastroesophageal reflux questionnaire score, and DeMeester scores, acid exposure time, lower esophageal sphincter pressure, esophagitis, proton pump inhibitors use, and patient satisfaction. RESULTS: This study comprised 37 studies, including 1732 patients. After ECSF, significant improvement in gastroesophageal reflux disease health-related quality of life score (mean difference [MD] = 18.27 95% CI: 14.81-21.74), gastroesophageal reflux questionnaire score (MD = 4.85 95% CI: 3.96-5.75), DeMeester score (MD = 42.34, 95% CI: 31.37-53.30), acid exposure time (MD = 7.98, 95% CI: 6.03-9.92), and lower esophageal sphincter pressure was observed (MD = -5.01, 95% CI: -8.39 to 1.62). The incidence of serious adverse effects after ECSF was 1.1% (95% CI: 0.9%-1.2%), and postoperatively, 67.4% (95% CI: 66.4%-68.2%) of patients could discontinue proton pump inhibitor-like drugs, and the treatment outcome was observed to be satisfactory in over 80% of the patients. Subgroup analyses of the various procedures showed that all 3 types improved several objective or subjective patient indicators. CONCLUSIONS: Based on the current meta-analysis, we conclude that rGERD can be safely and effectively treated with ECSF as an endoscopic procedure.


Assuntos
Cárdia , Refluxo Gastroesofágico , Humanos , Qualidade de Vida , Cicatriz/etiologia , Cicatriz/tratamento farmacológico , Refluxo Gastroesofágico/tratamento farmacológico , Endoscopia , Fundoplicatura/métodos , Resultado do Tratamento , Inibidores da Bomba de Prótons/uso terapêutico
19.
Hum Genet ; 143(3): 343-355, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38480539

RESUMO

Colorectal cancer (CRC) is the third most prevalent diagnosed cancer in men and second most prevalent cancer in women. H3K27ac alterations are more commonly than gene mutations in colorectal cancer. Most colorectal cancer genes have significant H3K27ac changes, which leads to an over-expression disorder in gene transcription. Over-expression of STEAP3 is involved in a variety of tumors, participating in the regulation of cancer cell proliferation and migration. The purpose of this work is to investigate the role of STEAP3 in the regulation of histone modification (H3K27ac) expression in colon cancer. Bioinformatic ChIP-seq, ChIP-qPCR and ATAC-seq were used to analyze the histone modification properties and gene accessibility of STEAP3. Western blot and qRT-PCR were used to evaluate relative protein and gene expression, respectively. CRISPR/Cas9 technology was used to knockout STEAP3 on colon cancer cells to analyze the effect of ATF3 on STEAP3. STEAP3 was over-expressed in colon cancer and associated with higher metastases and more invasive and worse stage of colon cancer. ChIP-seq and ChIP-qPCR analyses revealed significant enrichment of H3K27ac in the STEAP3 gene. In addition, knocking down STEAP3 significantly inhibits colon cancer cell proliferation and migration and down-regulates H3K27ac expression. ChIP-seq found that ATF3 is enriched in the STEAP3 gene and CRISPR/Cas9 technology used for the deletion of the ATF3 binding site suppresses the expression of STEAP3. Over-expression of STEAP3 promotes colon cancer cell proliferation and migration. Mechanical studies have indicated that H3K27ac and ATF3 are significantly enriched in the STEAP3 gene and regulate the over-expression of STEAP3.


Assuntos
Movimento Celular , Proliferação de Células , Neoplasias do Colo , Regulação Neoplásica da Expressão Gênica , Histonas , Humanos , Proliferação de Células/genética , Movimento Celular/genética , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Histonas/metabolismo , Histonas/genética , Acetilação , Feminino , Linhagem Celular Tumoral , Masculino , Fator 3 Ativador da Transcrição/genética , Fator 3 Ativador da Transcrição/metabolismo
20.
Neurol India ; 72(1): 102-109, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38443010

RESUMO

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelinating lesions in the white matter of the central nervous system. Studies have shown that exercise is beneficial for multiple sclerosis (MS). However, the molecular basis is largely unknown. MATERIALS AND METHODS: We integrated multiple blood and hippocampus transcriptome data from subjects with physical activity or MS. Transcription change associations between physical activity and MS were analyzed with bioinformatic methods including GSEA (Gene Set Enrichment Analysis) and GO (Gene Ontology) analysis. RESULTS: We find that exercise can specifically reverse immune-related genes in the hippocampus of MS patients, while this effect is not observable in blood. Moreover, many of these reversed genes encode immune-related receptors. Interestingly, higher levels of physical activity have more pronounced effects on the reversal of MS-related transcripts. CONCLUSIONS: The immune-response related genes or pathways in the hippocampus may be the targets of exercise in alleviating MS conditions, which may offer new therapeutic clues for MS.


Assuntos
Doenças Autoimunes , Esclerose Múltipla , Substância Branca , Humanos , Esclerose Múltipla/genética , Hipocampo , Exercício Físico
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