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Conjugated polymers are becoming popular near-infrared II (NIR-II) phototheranostic agents (PTAs) due to their numerous advantages, such as high photostability, large molar extinction coefficients, and excellent photothermal properties. However, the strong π-π interactions between the chains of the conjugated polymers resulted in their generally low NIR-II emission quantum yields (QY). Therefore, the synthesis of conjugated polymers with high QY is an interesting but challenging task. Herein, we proposed a spacer twisting strategy to realize ultrabright NIR-II polymer nanoparticles for fluorescence imaging-guided tumor phototheranostics. Theoretical calculations indicated that the polymer PY-IT has the largest dihedral angle between the largely π-conjugated skeleton and the spacer, which can effectively inhibit intermolecular π-π stacking, resulting in an improved QY as high as 16.5% in nanoparticles. In addition, PY-IT NPs can effectively perform NIR-II imaging and photothermal treatment of tumors. The work presents some valuable guides for achieving ultrabright NIR-II polymeric PTAs with high QY.
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BACKGROUND AND PURPOSE: Atherosclerosis is the basis of cardiovascular disease. Ferroptosis is a form of programmed cell death characterized by lipid peroxidation, which contributes to atherogenesis. The plant extract PNS (Panax notoginseng saponins), containing the main active ingredients of Panax notoginseng, exhibits anti-atherogenic properties. Herein, we determined whether PNS and its major components could attenuate atherosclerosis by suppressing ferroptosis and revealed the underlying mechanism(s). EXPERIMENTAL APPROACH: The anti-atherogenic effects of PNS and their association with inhibition of ferroptosis was determined in apoE-/- mice. In vitro, the anti-ferroptotic effect and mechanism(s) of PNS components were demonstrated in the presence of ferroptosis inducers. Expression of ferroptosis markers and the ubiquitination of Keap1 were evaluated in USP2-/- macrophages. Finally, the anti-atherogenic effect of USP2 knockout was determined by using USP2-/- mice treated with high-fat diet (HFD) and AAV-PCSK9. KEY RESULTS: PNS inhibited ferroptosis and atherosclerosis in vivo. PNS suppressed ferroptosis and ferroptosis-aggravated foam cell formation and inflammation in vitro. Mechanistically, PNS and its components activated Nrf2 by antagonizing Keap1, which was attributed to the inhibition of USP2 expression. USP2 knockout antagonized ferroptosis and ferroptosis-aggravated foam cell formation and inflammation, thus mitigating atherosclerosis. USP2 knockout abolished inhibitory effects of PNS on foam cell formation and inflammation in vitro. CONCLUSION AND IMPLICATIONS: PNS reduced USP2-mediated Keap1 de-ubiquitination and promoted Keap1 degradation, thereby activating Nrf2, improving iron metabolism and reducing lipid peroxidation, thus contributing to an anti-atherosclerotic outcome. Our study revealed the mechanism(s) underlying inhibition of ferroptosis and atherosclerosis by PNS.
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Background/purpose: Dental plaque is the main cause leading to the dental caries and periodontal diseases. The main purpose of this study was to test the efficacy of oral spray containing the antimicrobial peptide P-113 on the reduction of oral bacteria number and dental plaque formation in a randomized clinical assessment. Materials and methods: This study was divided into two parts. In Part A, we investigated the user experiences with the P-113 containing oral spray. In part B, 14 subjects in the experimental group used the P-113-containing oral spray, while 14 subjects in the control group used a placebo without the P-113 in a 4-week clinical trial. Participants were asked to use the P-113-containing oral spray or placebo 3 times per day and 5 times per use. Moreover, 3 check-ups and 2 washouts were carried out to evaluate the DMFT score, dental plaque weight, dental plaque index, and gingival index. Results: In part A, up to 91.8% of the subjects in the experimental group were satisfied with the use of the P-113-containing oral spray. In part B, based on our PacBio SMRT sequencing platform and DADA2 analysis, the numbers of Streptococcus and Porphyromonas in the experimental group were lower than those in the control group. In addition, decreased dental plaque weight, dental plaque index, and gingival index were all observed in the experimental group. Conclusion: The P-113-containing oral spray has the potential to reduce the dental caries and periodontal disease-related bacteria and to control the dental plaque formation.
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Water-soluble tomato concentrate (WSTC) has demonstrated beneficial effect on blood flow in healthy populations. The prospective, randomized, double-blind, and placebo-controlled clinical trial was conducted to explore the impact of WSTC on individuals with elevated cholesterol levels. Sixty participants aged 35-65 with high cholesterol were enrolled and evenly divided into a treatment group (FFG) and a placebo group (PCG). Over a 60-day period comprising a 45-day treatment phase followed by a 15-day observational follow-up. Participants in the FFG received 300 mg daily of Fruitflow tablets, while the PCG were received placebos. The study showed that there were no significant differences in baseline parameters between the FFG and PCG (p > 0.05). Post-intervention, the FFG exhibited significant reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 4.2% (SBP, p < 0.001) and 3.8% (DBP, p = 0.015), respectively, compared to the PCG (p = 0.041). These reductions were sustained during the follow-up period. In contrast, the PCG showed no significant changes in SBP and DBP (p > 0.05). Stratified analysis by hypertension status revealed a significant SBP reductions both hypertensive and non-hypertensive FFG subjects (p < 0.05), with a trend towards DBP reduction. No significant changes in SBP and DBP were observed in the PCG. Moreover, the FFG group showed a significant increase in high-density lipoprotein (HDL) cholesterol (p < 0.05), along with a marked reduction in both weight and body mass index (BMI) (p < 0.05). The FFG also showed decreased levels of homocysteine, high-sensitivity C-reactive protein, and fasting blood glucose compared to the PCG (p < 0.05). In conclusion, WSTC has the potential to lower blood pressure and cardiovascular risk profiles in hypercholesterolemic individuals, presenting a viable non-harmacological option for enhancing cardiovascular health. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=27052, identifier ChiCTR1800015904.
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Local curvature in graphene can enhance its reactivity and catalytic activity and can be induced by the adsorption of certain chemical species. By employing periodic density functional theory (DFT) calculations, we demonstrate that significant local curvature can be systematically observed when lanthanide atoms (the full series from La to Lu) are adsorbed on the Stone-Wales (SW) defect in graphene, contrary to that in defect-free graphene. Despite the typical high coordination numbers of lanthanide species, their hapticity is always η2 (and not η5, η6, or η7), where Ln atoms are adsorbed on the (7,7) junction, forming relatively short Ln···C separations. Contrary to the pristine graphene, the SW region undergoes considerable distortion and results in much stronger Ln bonding. The positive charge acquired by Ln atoms upon adsorption on SW is approximately 1.5 times larger than that on defect-free graphene. The high visibility of electron-rich lanthanide species in scanning tunneling microscopy images provides a means to locate SW defects in graphene samples experimentally.
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Three-dimensional charge-trapping (CT) NAND flash memory has attracted extensive attention owing to its unique merits, including huge storage capacities, large memory densities, and low bit cost. The reliability property is becoming an important factor for NAND flash memory with multi-level-cell (MLC) modes like triple-level-cell (TLC) or quad-level-cell (QLC), which is seriously affected by the intervals between program (P) and erase (E) operations during P/E cycles. In this work, the impacts of the intervals between P&E cycling under different temperatures and P/E cycles were systematically characterized. The results are further analyzed in terms of program disturb (PD), read disturb (RD), and data retention (DR). It was found that fail bit counts (FBCs) during the high temperature (HT) PD process are much smaller than those of the room temperature (RT) PD process. Moreover, upshift error and downshift error dominate the HT PD and RT PD processes, respectively. To improve the memory reliability of 3D CT TLC NAND, different intervals between P&E operations should be adopted considering the operating temperatures. These results could provide potential insights to optimize the lifetime of NAND flash-based memory systems.
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Calcium imaging has become a popular way to probe astrocyte activity, but few techniques holistically capture discrete calcium signals occurring across the astrocyte domain. Here, we introduce STARDUST, a pipeline for the spatio-temporal analysis of regional dynamics and unbiased sorting of transients from fluorescence recordings of astrocytes. We describe steps for installing software, detecting active pixel patches, obtaining region of activity (ROA) maps, and extracting time series from ROAs. We then detail procedures for extracting signal features using custom-made code.
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Astrócitos , Sinalização do Cálcio , Cálcio , Software , Astrócitos/metabolismo , Astrócitos/citologia , Cálcio/metabolismo , Animais , Sinalização do Cálcio/fisiologia , Processamento de Imagem Assistida por Computador/métodos , Análise Espaço-Temporal , CamundongosRESUMO
Coxiella burnetii (C. burnetii) is the causative agent of Q fever, a type of zoonoses withwidespread distribution. In 2019, a case of Q fever was diagnosed by metagenomic next-generation sequencing (mNGS) method in Xuyi County (Jiangsu province, China). The seroprevalence of previous fever patients and the molecular epidemiology of Coxiella in wild hedgehogs and harbouring ticks around the confirmed patient were detected to reveal the genetic characteristics and pathogenicity of the Coxiella strains. Four of the 90 serum samples (4.44%) were positive for specific C. burnetii IgM antibody, suggesting that local humans are at risk of Q fever. The positive rates of C. burnetii in hedgehogs and ticks were 21.9% (7/32) and 70.5% (122/173), respectively. At least 3 strains of Coxiella were found prevalent in the investigated area, including one new genotype of pathogenic C. burnetii (XYHT29) and two non-pathogenic Coxiella-like organisms (XYHT19 and XYHT3). XYHT29 carried by ticks and wild hedgehogs successfully infected mice, imposing a potential threat to local humans. XYHT19, a novel Coxiella-like microorganism, was first discovered in the world to co-infect with C. burnetii in Haemaphysalis flava. The study provided significant epidemic information that could be used for prevention and control strategies against Q fever for local public health departments and medical institutions.
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Coxiella burnetii , Ouriços , Febre Q , Carrapatos , Febre Q/epidemiologia , Febre Q/microbiologia , Coxiella burnetii/genética , Coxiella burnetii/isolamento & purificação , Animais , China/epidemiologia , Humanos , Carrapatos/microbiologia , Ouriços/microbiologia , Camundongos , Coinfecção/microbiologia , Coinfecção/epidemiologia , Feminino , Masculino , Estudos Soroepidemiológicos , Genótipo , Anticorpos Antibacterianos/sangue , Sequenciamento de Nucleotídeos em Larga Escala , Zoonoses/microbiologia , Zoonoses/epidemiologia , Coxiella/genética , Coxiella/isolamento & purificação , Epidemiologia Molecular , FilogeniaRESUMO
Erythropoietin (EPO), expressed in red blood progenitor cells, primarily regulates erythropoiesis by binding to its receptor. Besides anemia, recent studies have identified new therapeutic indications for EPO that are not connected to red blood cell formation. Elevated EPO levels harm bone homeostasis in adult organisms and are associated with increased osteoclast; however, the underlying molecular mechanisms remain unclear. This study demonstrated that EPO enhanced osteoclast differentiation and bone resorption in vitro. We showed that EPO promoted osteoclast formation by up-regulating PPARγ expression through activating the Jak2/ERK signaling pathway. Consistently, PPARγ antagonists rescued the hyperactivation of osteoclasts due to EPO, while PPARγ agonists reversed the EMP9-mediated decrease in osteoclast differentiation. Further, exposing female mice to EPO for two months led to a decrease in bone mass and increased osteoclast numbers. The present results suggested that EPO promotes osteoclastogenesis by regulating the Jak2/ERK/ PPARγ signaling pathway. From a clinical perspective, the risk of compromised bone health should be considered when using EPO to treat anemia in post-operative patients with intertrochanteric fractures of the femur, as it could significantly impact the patient's recovery and quality of life.
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Diferenciação Celular , Eritropoetina , Osteoclastos , PPAR gama , Eritropoetina/farmacologia , Eritropoetina/metabolismo , Animais , PPAR gama/metabolismo , Osteoclastos/metabolismo , Osteoclastos/efeitos dos fármacos , Camundongos , Feminino , Diferenciação Celular/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Janus Quinase 2/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Humanos , Regulação para Cima/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Reabsorção Óssea/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Background: Guided bone regeneration (GBR) uses bone grafts and barrier membranes to block soft tissue invasion and eventually create a new bone. Some studies indicate that a porcine bone graft demonstrates excellent biocompatibility and holds promise as a xenograft for GBR. However, only a few studies have investigated the effectiveness of this biomaterial after magnesium coating in improving osteoblast performance. Aim: This study aimed to prove that the hydrothermal method can be used to coat magnesium oxide (MgO) on the surface of a porcine graft and enhance the biomaterial's property for better osteogenic differentiation of osteoblasts in vitro. Materials and Method: A porcine bone graft was produced, and the hydrothermal method was used to coat 2 mM and 5 mM of MgO on the graft. Material physiochemistry and biocompatibility analyses were performed at days 1, 3, and 5. Results: pH value assay results suggested that MgO slightly increased the alkalinity of the graft. SEM images showed that MgO with some surface roughness was coated on the porcine bone surface, and EDX indicated that the Mg and O element percentages increased by about 5% and 9%, respectively. The porcine graft coated with MgO was rougher than an uncoated porcine graft. FTIR analysis of the porcine graft implied that its chemical structure did not change due to MgO hydrothermal processing. Cell viability assay illustrated the highest cell proliferation with the porcine graft with 5 mM MgO (P < 0.001), and good cell attachment was observed on the graft with immunofluorescence using confocal laser scanning microscopy. Cell differentiation assay results revealed that the porcine graft with 5 mM MgO had the highest alkaline phosphate activity (P < 0.0001) among the uncoated porcine graft and the porcine graft with 2 mM MgO. Relative quantitative polymerase chain reaction (qPCR) at days 1 and 5 revealed upregulated osteoblast gene expression with a statistically significant difference. Conclusion: The porcine graft hydrothermally coated with 5 mM MgO was more biocompatible and enhanced osteoblast differentiation. Thus, the findings of this study indicate that a porcine graft with 5 mM MgO has great potential as a bio-bone graft for guided bone regeneration.
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Listeriosis is highly prevalent in the animal farming industry, with Listeria monocytogenes as the causative pathogen. To identify potential therapeutic targets for LM infection, we investigated the mechanisms of LM infection in goat uteri. We inoculated a group of goats with LM via jugular vein injection, isolated and raised them, and subsequently collected sterile samples of their uterine tissue after they exhibited clinical symptoms of LM infection. We used Giemsa staining, immunohistochemical staining, real-time qPCR, and Western blotting as experimental methods.First, we investigated the mechanism of Listeria monocytogenes (LM) infection in the goat uterus by examining the expression levels of listeriolysin O, E-cadherin, and tyrosine kinase c-Met in the uterus.Furthermore, we investigated the impact of LM infection on uterine autophagy and cell apoptosis. The results indicate that the injection of LM into the goats' jugular veins leads to LM infection in the goats' uteri. During LM survival inside the goat uterine cells, there is a significant increase in the expression levels of LLO, E-cadherin, and c-Met in the host uterine tissue. This suggests that LM may potentially infect goat uteri through the InlA/E-cadherin and InlB/c-Met pathways. Furthermore, LM infection increases the levels of apoptosis and autophagy in goat uteri. Apoptosis genes Bcl-2 and Bax, as well as autophagy-related genes LC3B, PINK1, and Parkin, exhibit varying degrees of changes in localization and expression in goat uteri, mediating the occurrence of apoptotic and autophagic responses.
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Owing to their nontoxicity, environmental friendliness, and high biocompatibility, physically cross-linked hydrogels have become popular research materials; however, their high water content and high free volume, along with the weak bonding interactions inherent to ordinary physically cross-linked hydrogels, limit their application in fields such as flexible devices, packaging materials, and substance transport regulation. Here, a structural barrier approach based on directional freezing-assisted salting out was proposed, and the directional structure significantly enhanced the barrier performance of the hydrogel. When the direction of substance diffusion was perpendicular to the pore channel structure of the directional freezing-PVA hydrogel (DFPVA), the Cl- transmission rate was 57.2% for the uniform freezing-PVA hydrogel (UFPVA). By adjusting the concentration of the salting-out solution and the salting-out time, the crystallinity and crystal domain size of the hydrogel could be further changed, optimizing and regulating the barrier performance of the hydrogel, with the best Cl- unit permeability being 36.02 mg mm per cm2 per day. Additionally, DFPVA had excellent mechanical properties (stress of 6.47 ± 1.04 MPa, strain of 625.85 ± 61.58%, toughness of 25.77 ± 3.72 MPa). Due to the barrier and mechanical properties of the direct structure, DFPVA is suitable as a drug carrier for slow drug release in vitro.
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OBJECTIVE: Reconstruction of soft tissue defects after total parotidectomy requires a feasible and effective pedicled flap with sufficient volume. In this study, we introduce a modified submandibular gland flap (SMGF) for functional reconstruction of soft tissue defects resulting from total parotidectomy. MATERIALS AND METHODS: This study included 12 patients diagnosed with parotid gland carcinoma undergoing total parotidectomy and ipsilateral selective neck dissection. The modified SMGF was harvested and transferred to the parotid bed. This procedure was coupled with anastomosis between the parotid gland duct and Wharton's duct. The feasibility of the surgery, postoperative complications, facial profile restoration, and salivary secretion were assessed. RESULTS: All SMGFs pedicled only over the proximal facial artery survived without major complications. Facial profiles were well-restored, and salivary secretion was partially reserved. During the postoperative follow-up, no tumor recurrence was observed in any of the cases, and the volume of the SMGFs did not show obvious atrophy. CONCLUSIONS: The modified SMGF is a viable solution for volume restoration and functional reconstruction after total parotidectomy. CLINICAL RELEVANCE: This modified technique is simple and feasible for the functional reconstruction of soft tissue defects after total parotidectomy compared to other flaps and is worthy of clinical promotion.
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Nonadiabatic molecular dynamics (NA-MD) is a powerful tool to model far-from-equilibrium processes, such as photochemical reactions and charge transport. NA-MD application to condensed phase has drawn tremendous attention recently for development of next-generation energy and optoelectronic materials. Studies of condensed matter allow one to employ efficient computational tools, such as density functional theory (DFT) and classical path approximation (CPA). Still, system size and simulation timescale are strongly limited by costly ab initio calculations of electronic energies, forces, and NA couplings. We resolve the limitations by developing a fully machine learning (ML) approach in which all the above properties are obtained using neural networks based on local descriptors. The ML models correlate the target properties for NA-MD, implemented with DFT and CPA, directly to the system structure. Trained on small systems, the neural networks are applied to large systems and long timescales, extending NA-MD capabilities by orders of magnitude. We demonstrate the approach with dependence of charge trapping and recombination on defect concentration in MoS2. Defects provide the main mechanism of charge losses, resulting in performance degradation. Charge trapping slows with decreasing defect concentration; however, recombination exhibits complex dependence, conditional on whether it occurs between free or trapped charges, and relative concentrations of carriers and defects. Delocalized shallow traps can become localized with increasing temperature, changing trapping and recombination behavior. Completely based on ML, the approach bridges the gap between theoretical models and realistic experimental conditions and enables NA-MD on thousand-atom systems and many nanoseconds.
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The multiple relaxation processes of excited states are a bridge connecting molecular structures and properties, providing enormous application potential for organic luminogens. However, a systematic understanding and manipulation of the relationship between the molecular structure, excited state relaxation processes, and properties of organic luminogens is still lacking. Herein, we report a strategy for manipulating excited state electronic configurations through the regulation of the sulfur oxidation state to construct eminent organic type I PSs. Combined with the experimental results and theoretical calculations, we have successfully revealed the decisive role of high sulfur oxidation states in promoting ROS production capacity. Impressively, a higher sulfur oxidation state can reduce the singlet-triplet energy gap (ΔE ST), increase the matching degree of transition configurations, promote the changes of the excited state electronic configurations, and boost the effective ISC proportion by enhancing intramolecular interactions. Therefore, DBTS2O with the highest sulfur oxidation state exhibits the strongest type I ROS generation ability. Additionally, guided by our strategy, a water-soluble PS (2OA) is designed and synthesized, showing selective imaging capacity and photokilling ability against Gram-positive bacteria. This study broadens the horizons for both molecular design and mechanism study of high-performance organic type I PSs.
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Zero-dimensional (0D) hybrid metal halides have been emerged as room-temperature phosphorescence (RTP) materials, but synchronous optimization of multiple phosphorescence performance in one structural platform remains less resolved, and stable RTP activity in aqueous medium is also unrealized due to serious instability toward water and oxygen. Herein, we demonstrated a photophysical tuning strategy in a new 0D hybrid zinc halide family of (BTPP)2ZnX4 (BTPP = benzyltriphenylphosphonium, X = Cl and Br). Infrequently, the delicate combination of organic and inorganic species enables this family to display multiple ultralong green afterglow and efficient self-trapped exciton (STE) associated cyan phosphorescence. Compared with inert luminescence of [BTPP]+ cation, incorporation of anionic [ZnX4]2- effectively enhance the spin-orbit coupling effect, which significantly boosts the photoluminescence quantum yield (PLQY) up to 30.66% and 54.62% for afterglow and phosphorescence, respectively. Synchronously, the corresponding luminescence lifetime extend to 143.94 ms and 0.308 µs surpassing the indiscernible phosphorescence of [BTPP]X salt. More importantly, this halide family presents robust RTP emission with nearly unattenuated PLQY in water and harsh condition (acid and basic aqueous solution) over half a year. The highly efficient integrated afterglow and STE phosphorescence as well as ultrahigh aqueous state RTP realize multiple anti-counterfeiting applications in wide chemical environments.
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Concise and scalable formal syntheses of (-)-quinocarcinamide and (-)-quinocarcin have been achieved in 9 steps with 9% overall yield from simple commercially available chemicals. The synthetic strategy features an ortho-regioselective Pictet-Spengler cyclization for the construction of the tetrahydroisoquinoline skeleton, a stereoselective formal intramolecular [3 + 2] cross cycloaddition of cyclopropane 1,1-diester with an imine for the construction of the 3,8-diazabicyclo[3.2.1]octane skeleton.
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TP53 mutation (TP53-mut) correlates with inferior survival in many cancers, whereas its prognostic role in diffuse large B-cell lymphoma (DLBCL) is still in controversy. Therefore, more precise risk stratification needs to be further explored for TP53-mut DLBCL patients. A set of 2637 DLBCL cases from multiple cohorts, was enrolled in our analysis. Among the 2637 DLBCL patients, 14.0% patients (370/2637) had TP53-mut. Since missense mutations account for the vast majority of TP53-mut DLBCL patients, and most non-missense mutations affect the function of the P53 protein, leading to worse survival rates, we distinguished patients with missense mutations. A TP53 missense mutation risk model was constructed based on a 150-combination machine learning computational framework, demonstrating excellent performance in predicting prognosis. Further analysis revealed that patients with high-risk missense mutations are significantly associated with early progression and exhibit dysregulation of multiple immune and metabolic pathways at the transcriptional level. Additionally, the high-risk group showed an absolutely suppressed immune microenvironment. To stratify the entire cohort of TP53-mut DLBCL, we combined clinical characteristics and ultimately constructed the TP53 Prognostic Index (TP53PI) model. In summary, we identified the truly high-risk TP53-mut DLBCL patients and explained this difference at the mutation and transcriptional levels.
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Linfoma Difuso de Grandes Células B , Proteína Supressora de Tumor p53 , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Humanos , Proteína Supressora de Tumor p53/genética , Prognóstico , Mutação de Sentido Incorreto/genética , Mutação/genética , Microambiente Tumoral/genética , Masculino , Feminino , Fatores de Risco , Pessoa de Meia-IdadeRESUMO
We designed two series of NIR-II PTAs with D-A or D-A-D structures, in which the introduction of thiophene promotes a bathochromic shift of emission into the NIR-II region, helps to improve the cellular uptake of the PTAs and facilitates NIR-II imaging-guided PDT/PTT cancer phototherapy.
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Raios Infravermelhos , Tiofenos , Tiofenos/química , Humanos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Fotoquimioterapia , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fototerapia , Imagem Óptica , Estrutura Molecular , Animais , Nanomedicina TeranósticaRESUMO
The mislocalization of proteins leads to breast cancer, one of the world's most prevalent cancers, which can be identified from immunohistochemical images. Here, based on the deep learning framework, location prediction models were constructed using the features of breast immunohistochemical images. Ultimately, six differentially localized proteins that with stable differentially predictive localization, maximum localization differences, and whose predicted results are not affected by removing a single image are obtained (CCNT1, NSUN5, PRPF4, RECQL4, UTP6, ZNF500). Further verification reveals that these proteins are not differentially expressed, but are closely associated with breast cancer and have great classification performance. Potential mechanism analysis shows that their co-expressed or co-located proteins and RNAs may affect their localization, leading to changes in interactions and functions that further causes breast cancer. They have the potential to help shed light on the molecular mechanisms of breast cancer and provide assistance for its early diagnosis and treatment.