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1.
Nat Commun ; 15(1): 2110, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454003

RESUMO

Pilot-diesel-ignition ammonia combustion engines have attracted widespread attentions from the maritime sector, but there are still bottleneck problems such as high unburned NH3 and N2O emissions as well as low thermal efficiency that need to be solved before further applications. In this study, a concept termed as in-cylinder reforming gas recirculation is initiated to simultaneously improve the thermal efficiency and reduce the unburned NH3, NOx, N2O and greenhouse gas emissions of pilot-diesel-ignition ammonia combustion engine. For this concept, one cylinder of the multi-cylinder engine operates rich of stoichiometric and the excess ammonia in the cylinder is partially decomposed into hydrogen, then the exhaust of this dedicated reforming cylinder is recirculated into the other cylinders and therefore the advantages of hydrogen-enriched combustion and exhaust gas recirculation can be combined. The results show that at 3% diesel energetic ratio and 1000 rpm, the engine can increase the indicated thermal efficiency by 15.8% and reduce the unburned NH3 by 89.3%, N2O by 91.2% compared to the base/traditional ammonia engine without the proposed method. At the same time, it is able to reduce carbon footprint by 97.0% and greenhouse gases by 94.0% compared to the traditional pure diesel mode.

2.
Sci Bull (Beijing) ; 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38531717

RESUMO

Developing low-power FETs holds significant importance in advancing logic circuits, especially as the feature size of MOSFETs approaches sub-10 nanometers. However, this has been restricted by the thermionic limitation of SS, which is limited to 60 mV per decade at room temperature. Herein, we proposed a strategy that utilizes 2D semiconductors with an isolated-band feature as channels to realize sub-thermionic SS in MOSFETs. Through high-throughput calculations, we established a guiding principle that combines the atomic structure and orbital interaction to identify their sub-thermionic transport potential. This guides us to screen 192 candidates from the 2D material database comprising 1608 systems. Additionally, the physical relationship between the sub-thermionic transport performances and electronic structures is further revealed, which enables us to predict 15 systems with promising device performances for low-power applications with supply voltage below 0.5 V. This work opens a new way for the low-power electronics based on 2D materials and would inspire extensive interests in the experimental exploration of intrinsic steep-slope MOSFETs.

3.
Adv Healthc Mater ; : e2400414, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38412402

RESUMO

Recently, magnetically actuated micro/nanorobots hold extensive promises in biomedical applications due to their advantages of noninvasiveness, fuel-free operation, and programmable nature. While effectively promised in various fields such as targeted delivery, most past investigations are mainly displayed in magnetic control of individual micro/nanorobots. Facing practical medical use, the micro/nanorobots are required for the development of swarm control in a closed-loop control manner. This review outlines the recent developments in magnetic micro/nanorobot swarms, including their actuating fundamentals, designs, controls, and biomedical applications. The fundamental principles and interactions involved in the formation of magnetic micro/nanorobot swarms are discussed first. The recent advances in the design of artificial and biohybrid micro/nanorobot swarms, along with the control devices and methods used for swarm manipulation, are presented. Furthermore, biomedical applications that have the potential to achieve clinical application are introduced, such as imaging-guided therapy, targeted delivery, embolization, and biofilm eradication. By addressing the potential challenges discussed toward the end of this review, magnetic micro/nanorobot swarms hold promise for clinical treatments in the future.

4.
Food Chem ; 443: 138533, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38320376

RESUMO

Herein, a self-enhanced molecularly imprinted polymer luminescence (MIP-ECL) sensing platform based on gold-copper doped Tb-MOFs (Au@Cu:Tb-MOFs) was constructed for ultra-sensitive detection of chlorpyrifos (CPF). In this work, Au@Cu:Tb-MOFs as co-reaction promoters greatly improve the ECL emission signal, while Au@Cu:Tb-MOFs were used as cathode emitters. And chlorpyrifos and 4,7-bis(thiophene-2-yl)benzo [c][1,2,5] thiadiazole were electropolymerized on electrode surface to form MIP, where this films with thiophene derivatives could greatly improve ECL signal. Notably, the introduction of MIP as recognition elements enabled specific identification of target analytes, in which molecular docking technique validated target analyte and functional monomers are tightly bound through Pi-alkyl interaction. As the concentration of CPF increases, the ECL signal gradually decreases, showing a good linear relationship in the range of 0.1-106 pg/mL with a low detection limit (LOD) of 0.029 pg/mL. Moreover, actual sample testing experiment of this method displayed a special correlation in organophosphorus detection and development potential in actual sample analysis.


Assuntos
Técnicas Biossensoriais , Clorpirifos , Elementos da Série dos Lantanídeos , Impressão Molecular , Luminescência , Cobre , Ouro , Impressão Molecular/métodos , Medições Luminescentes/métodos , Simulação de Acoplamento Molecular , Limite de Detecção , Tiofenos , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos
6.
Adv Sci (Weinh) ; 11(14): e2306935, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38321783

RESUMO

The evolution of pathway enzymes enhances the biosynthesis of high-value chemicals, crucial for pharmaceutical, and agrochemical applications. However, unpredictable evolutionary landscapes of pathway genes often hinder successful evolution. Here, the presence of complex epistasis is identifued within the representative naringenin biosynthetic pathway enzymes, hampering straightforward directed evolution. Subsequently, a biofoundry-assisted strategy is developed for pathway bottlenecking and debottlenecking, enabling the parallel evolution of all pathway enzymes along a predictable evolutionary trajectory in six weeks. This study then utilizes a machine learning model, ProEnsemble, to further balance the pathway by optimizing the transcription of individual genes. The broad applicability of this strategy is demonstrated by constructing an Escherichia coli chassis with evolved and balanced pathway genes, resulting in 3.65 g L-1 naringenin. The optimized naringenin chassis also demonstrates enhanced production of other flavonoids. This approach can be readily adapted for any given number of enzymes in the specific metabolic pathway, paving the way for automated chassis construction in contemporary biofoundries.


Assuntos
Escherichia coli , Flavonoides , Escherichia coli/genética , Redes e Vias Metabólicas , Aprendizado de Máquina
7.
IEEE Trans Med Imaging ; PP2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38373130

RESUMO

Score-based generative model (SGM) has demonstrated great potential in the challenging limited-angle CT (LA-CT) reconstruction. SGM essentially models the probability density of the ground truth data and generates reconstruction results by sampling from it. Nevertheless, direct application of the existing SGM methods to LA-CT suffers multiple limitations. Firstly, the directional distribution of the artifacts attributing to the missing angles is ignored. Secondly, the different distribution properties of the artifacts in different frequency components have not been fully explored. These drawbacks would inevitably degrade the estimation of the probability density and the reconstruction results. After an in-depth analysis of these factors, this paper proposes a Wavelet-Inspired Score-based Model (WISM) for LA-CT reconstruction. Specifically, besides training a typical SGM with the original images, the proposed method additionally performs the wavelet transform and models the probability density in each wavelet component with an extra SGM. The wavelet components preserve the spatial correspondence with the original image while performing frequency decomposition, thereby keeping the directional property of the artifacts for further analysis. On the other hand, different wavelet components possess more specific contents of the original image in different frequency ranges, simplifying the probability density modeling by decomposing the overall density into component-wise ones. The resulting two SGMs in the image-domain and wavelet-domain are integrated into a unified sampling process under the guidance of the observation data, jointly generating high-quality and consistent LA-CT reconstructions. The experimental evaluation on various datasets consistently verifies the superior performance of the proposed method over the competing method.

8.
Natl Sci Rev ; 11(3): nwae001, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38312376

RESUMO

This Perspective aims to provide a concise survey of current progress and outlook future directions in high-performance transistors and integrated circuits (ICs) based on 2D semiconductors.

9.
Science ; 383(6682): eadj9198, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38300992

RESUMO

Mapping single-neuron projections is essential for understanding brain-wide connectivity and diverse functions of the hippocampus (HIP). Here, we reconstructed 10,100 single-neuron projectomes of mouse HIP and classified 43 projectome subtypes with distinct projection patterns. The number of projection targets and axon-tip distribution depended on the soma location along HIP longitudinal and transverse axes. Many projectome subtypes were enriched in specific HIP subdomains defined by spatial transcriptomic profiles. Furthermore, we delineated comprehensive wiring diagrams for HIP neurons projecting exclusively within the HIP formation (HPF) and for those projecting to both intra- and extra-HPF targets. Bihemispheric projecting neurons generally projected to one pair of homologous targets with ipsilateral preference. These organization principles of single-neuron projectomes provide a structural basis for understanding the function of HIP neurons.


Assuntos
Axônios , Mapeamento Encefálico , Hipocampo , Neurônios , Animais , Camundongos , Axônios/fisiologia , Axônios/ultraestrutura , Hipocampo/ultraestrutura , Neurônios/classificação , Neurônios/ultraestrutura , Análise de Célula Única/métodos , Rede Nervosa , Masculino , Camundongos Endogâmicos C57BL
10.
J Cancer Res Clin Oncol ; 150(2): 43, 2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38280970

RESUMO

OBJECTIVE: Given real-world limitations in programmed death-ligand 1 (PD-L1) testing, concordance studies between PD-L1 assays are needed. We undertook comparisons of PD-L1 assays (DAKO22C3, Ventana SP263, Ventana SP142, E1L3N) among observers in esophageal squamous cell carcinoma (ESCC) to provide information on the analytical and clinical comparability of four PD-L1 IHC assays. METHODS: Paraffin embedded samples of 50 cases of esophageal squamous cell carcinoma were obtained, satined with all four PD-L1 assays. PD-L1 was evaluated by 68 pathologists from 19 different hospitals. PD-L1 expression was assessed for combined positive score (CPS). RESULTS: The expression sensitivity of SP263 was the highest in ESCC, followed by 22C3, E1L3N and SP142. Taking CPS 10 as the critical value, inter-observer concordance for CPS scores among 68 physicians was assessed for the 22C3, SP263, SP142, and E1L3N assays, yielding values of 0.777, 0.790, 0.758, and 0.782, respectively. In the comparison between assays, the overall CPS scores concordance rates between 22C3 and SP263, SP142, and E1L3N were 0.896, 0.833, and 0.853, respectively. 22C3 and SP263 have high concordance, with OPA of 0.896, while E1L3N and SP142 have the highest concordance, with OPA of 0.908. CONCLUSION: In ESCC, the concordance of PD-L1 evaluation among observers is good, and the immune cell score is still an important factor affecting the concordance of interpretation among observers. Cases near the specific threshold are still the difficult problem of interpretation. SP263 had the highest CPS score of the four assays. SP263 cannot identify all 22C3 positive cases, but had good concordance with 22C3.E1L3N and SP142 showed high concordance.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias Pulmonares , Humanos , Imuno-Histoquímica , Antígeno B7-H1 , Patologistas , Biomarcadores Tumorais/metabolismo , Neoplasias Pulmonares/patologia
11.
Cell Rep ; 43(2): 113712, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38294903

RESUMO

Adoptive cell therapies are emerging forms of immunotherapy that reprogram T cells for enhanced antitumor responses. Although surface programmed cell death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) engagement inhibits antitumor immunity, the role of cell-intrinsic PD-L1 in adoptive T cell therapy remains unknown. Here, we found that intracellular PD-L1 was enriched in tumor-infiltrating CD8+ T cells of cancer patients. PD-L1 ablation promoted antitumor immune responses and the maintenance of an effector-like state of therapeutic CD8+ T cells, while blockade of surface PD-L1 was unable to impact on their expansion and function. Moreover, cell-intrinsic PD-L1 impeded CD8+ T cell activity, which partially relied on mTORC1 signaling. Furthermore, endogenous tumor-reactive CD8+ T cells were motivated by BATF3-driven dendritic cells after adoptive transfer of PD-L1-deficient therapeutic CD8+ T cells. This role of cell-intrinsic PD-L1 in therapeutic CD8+ T cell dysfunction highlights that disrupting cell-intrinsic PD-L1 in CD8+ T cells represents a viable approach to improving T cell-based cancer immunotherapy.


Assuntos
Linfócitos T CD8-Positivos , Neoplasias , Humanos , Antígeno B7-H1 , Imunoterapia , Terapia Baseada em Transplante de Células e Tecidos , Proteínas de Membrana , Neoplasias/terapia
12.
Sci Total Environ ; 918: 170295, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38278240

RESUMO

Microbial anabolism and catabolism regulate the accumulation and dynamics of soil organic carbon (SOC). However, very little attention has been paid to the role of microbial functional traits in the accumulation and dynamics of SOC in forest soils. In this study, nine forest soils were selected at three altitudes (600 m, 1200 m, and 1500 m) and three soil depths (0-15 cm, 15-30 cm, and 30-45 cm) located in Jiugong Mountain. Vertical traits of functional genes encoding microbial carbohydrate-active enzymes (CAZymes) were observed using metagenomic sequencing. Soil amino sugars were used as biomarkers to indicate microbial residue carbon (MRC). The results showed that GH1 (ß-glucosidase: 147.49 TPM) and GH3 (ß-glucosidase: 109.09 TPM) were the dominant genes for plant residue decomposition, and their abundance increased with soil depth and peaked in the deep soil at 600 m (GH1: 147.89 TPM; GH3: 109.59 TPM). The highest abundance of CAZymes for fungal and bacterial residue decomposition were GH18 (chitinase: 30.81 TPM) and GH23 (lysozyme: 58.02 TPM), respectively. The abundance of GH18 increased with soil depth, while GH23 showed the opposite trend. Moreover, MRC accumulation was significantly positively correlated with CAZymes involved in the degradation of hemicellulose (r = 0.577, p = 0.002). Compared with the soil before incubation, MRC in the topsoil at the low and middle altitudes after incubation increased by 4 % and 8 %, respectively, while MRC in the soils at 1500 m tended to decrease (p > 0.05). The mineralization capacity of SOC at 1500 m was significantly higher than that at 1200 m and 600 m (p < 0.05). Our results suggested that microbial function for degrading plant residue components, especially hemicellulose and lignin, contributed greatly to SOC accumulation and dynamics. These results were vital for understanding the roles of microbial functional traits in C cycling in forest.


Assuntos
Carbono , Celulases , Carbono/química , Solo/química , Microbiologia do Solo , Florestas , Carboidratos
13.
BMC Genomics ; 25(1): 4, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166640

RESUMO

BACKGROUND: Penicillium chrysogenum is a filamentous fungal species with diverse habitats, yet little is known about its genetics in adapting to extreme subseafloor sedimental environments. RESULTS: Here, we report the discovery of P. chrysogenum strain 28R-6-F01, isolated from deep coal-bearing sediments 2306 m beneath the seafloor. This strain possesses exceptional characteristics, including the ability to thrive in extreme conditions such as high temperature (45 °C), high pressure (35 Mpa), and anaerobic environments, and exhibits broad-spectrum antimicrobial activity, producing the antibiotic penicillin at a concentration of 358 µg/mL. Genome sequencing and assembly revealed a genome size of 33.19 Mb with a GC content of 48.84%, containing 6959 coding genes. Comparative analysis with eight terrestrial strains identified 88 unique genes primarily associated with penicillin and aflatoxins biosynthesis, carbohydrate degradation, viral resistance, and three secondary metabolism gene clusters. Furthermore, significant expansions in gene families related to DNA repair were observed, likely linked to the strain's adaptation to its environmental niche. CONCLUSIONS: Our findings provide insights into the genomic and biological characteristics of P. chrysogenum adaptation to extreme anaerobic subseafloor sedimentary environments, such as high temperature and pressure.


Assuntos
Penicillium chrysogenum , Penicillium chrysogenum/genética , Genômica , Genoma Fúngico , Genes Fúngicos , Penicilinas/metabolismo
14.
Glob Health Res Policy ; 9(1): 5, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38246986

RESUMO

BACKGROUND: China bears a high burden of both hepatitis B virus (HBV) infection and type 2 diabetes mellitus (T2DM). T2DM accelerates the progression of liver disease among individuals infected with HBV. This study aims to assess the excess disease burden caused by comorbid T2DM among HBV-infected individuals in China. METHODS: We estimated the disease burden of HBV and its complications in China from 2006 to 2030 using individual-based Markov models. The baseline population consisted of 93 million HBV-infected individuals derived from the 2006 National Serological Epidemiological Survey. We developed two models: one incorporated the impact of T2DM on the disease progression of HBV infection, while the other did not consider the impact of T2DM. By comparing the outcomes between these two models, we estimated the excess disease burden attributable to comorbid T2DM among HBV-infected individuals. RESULTS: The incidence of severe HBV complications, including cirrhosis, hepatocellular carcinoma (HCC), and liver-related deaths, exhibited an increasing trend from 2006 to 2030 among the Chinese HBV-infected population. Comorbid T2DM increased the annual incidence and cumulative cases of severe HBV complications. From 2006 to 2022, comorbid T2DM caused 791,000 (11.41%), 244,000 (9.27%), 377,000 (8.78%), and 796,000 (12.19%) excess cases of compensated cirrhosis, decompensated cirrhosis, HCC, and liver-related deaths, respectively. From 2023 to 2030, comorbid T2DM is projected to result in an 8.69% excess in severe HBV complications and an 8.95% increase in liver-related deaths. Among individuals aged 60 and older at baseline, comorbid T2DM led to a 21.68% excess in severe HBV complications and a 28.70% increase in liver-related deaths from 2006 to 2022, with projections indicating a further 20.76% increase in severe HBV complications and an 18.31% rise in liver-related deaths over the next seven years. CONCLUSIONS: Comorbid T2DM imposes a substantial disease burden on individuals with HBV infection in China. Healthcare providers and health policymakers should develop and implement tailored strategies for the effective management and control of T2DM in individuals with HBV infection.


Assuntos
Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , Humanos , Pessoa de Meia-Idade , Idoso , Hepatite B Crônica/complicações , Hepatite B Crônica/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Vírus da Hepatite B , Cirrose Hepática/epidemiologia , China/epidemiologia , Efeitos Psicossociais da Doença
15.
Antiviral Res ; 221: 105763, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38008192

RESUMO

Development of new anti-hepatitis B virus (HBV) drugs that target viral capsid assembly is a very active research field. We identify a novel phthalazinone derivative, compound 5832, as a potent HBV inhibitor. In this study, we intend to elaborate the antiviral effect and mechanism of 5832 against HBV in vitro and in vivo. Compound 5832 treatment induces the formation of genome-free empty capsid by interfering with the core protein assembly domain, which significantly decreases the extracellular and intracellular HBV DNA. In the AAV-HBV transduced mouse model, 5832 suppresses serum HBV DNA after 4-week treatment, and decreases HBsAg and HBeAg levels. 5832 treatment also reduces intrahepatic HBV RNA, DNA and HBcAg levels. During the follow-up period after treatment withdrawal, serum antigen levels demonstrated no increase. We demonstrate 5832 treatment could active apoptotic signaling by elevating the expression of death receptor 5 (DR5), which participated in corresponding HBcAg-positive hepatocyte eradication. Phthalazinone derivative 5832 may serve as a promising anti-HBV drug candidate to improve the treatment options for chronic HBV infection.


Assuntos
Hepatite B Crônica , Hepatite B , Camundongos , Animais , Vírus da Hepatite B , Antígenos do Núcleo do Vírus da Hepatite B/metabolismo , Capsídeo , DNA Viral/genética , Proteínas do Capsídeo/metabolismo , Antígenos de Superfície da Hepatite B , Antivirais/uso terapêutico
16.
Breast Cancer Res Treat ; 203(2): 373-381, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37843776

RESUMO

OBJECTIVE: The aim of this study is to evaluate the clinicopathological features and prognostic significance of HER2 low, fibrotic focus (FF), and tumor-infiltrating lymphocytes (TILs) in patients with HER2-negative breast cancer. METHODS: We retrospectively reviewed the data of 293 patients with HER2-negative, stage I-II, invasive breast cancer of non-specific types. The HER2-negative cases were classified into HER2 low and HER2 0. Digital analysis of hematoxylin-eosin stained whole slide images was used to evaluate the FF expression. TILs were also evaluated using the Whole Slide Image. Furthermore, the association between HER2 low, FF, and TILs as well as their prognostic significance were analyzed. RESULTS: The study cohort included 178 cases (60.8%) with HER2 low and 115 cases (39.2%) with HER2 0. Older age, lower Nottingham histological grade (NHG), estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, and hormone receptor (HR) positivity were all associated with HER2 low. FF was correlated with older age, intermediate and low NHG, vascular invasion, HR positivity, HER2 low status, high Ki67 expression, and low TILs. Univariate survival analysis showed that FF was significantly associated with shorter progression-free survival (PFS). Stratified analysis indicated that in the HR-negative and HR-positive groups, HER2 status and TILs did not affect PFS. DFS was longer in patients without FF compared to those with FF in the HR-positive (hazard ratio [HR] = 0.313) and HER2 low (HR = 0.272) groups. DFS was also significantly longer in patients without FF compared to those with FF in the HR-negative (HR = 0.069) and HER2 0 groups (HR = 0.129). CONCLUSION: The results indicated that the HER2 low status and the TILs expression did not impact prognosis. However, patients with FF exhibited distinct biological characteristics and prognostic significance, particularly in the HR-negative and HER2 0 groups. This provides a rationale for accurate diagnosis and treatment of HER2-negative breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Prognóstico , Estudos Retrospectivos , Receptor ErbB-2/metabolismo , Linfócitos do Interstício Tumoral , Intervalo Livre de Doença
18.
Adv Sci (Weinh) ; 11(10): e2305100, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38145961

RESUMO

Molecular diodes are of considerable interest for the increasing technical demands of device miniaturization. However, the molecular diode performance remains contact-limited, which represents a major challenge for the advancement of rectification ratio and conductance. Here, it is demonstrated that high-quality ultrathin organic semiconductors can be grown on several classes of metal substrates via solution-shearing epitaxy, with a well-controlled number of layers and monolayer single crystal over 1 mm. The crystals are atomically smooth and pinhole-free, providing a native interface for high-performance monolayer molecular diodes. As a result, the monolayer molecular diodes show record-high rectification ratio up to 5 × 108 , ideality factor close to unity, aggressive unit conductance over 103 S cm-2 , ultrahigh breakdown electric field, excellent electrical stability, and well-defined contact interface. Large-area monolayer molecular diode arrays with 100% yield and excellent uniformity in the diode metrics are further fabricated. These results suggest that monolayer molecular crystals have great potential to build reliable, high-performance molecular diodes and deeply understand their intrinsic electronic behavior.

19.
Diagn Pathol ; 18(1): 131, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38053121

RESUMO

BACKGROUND: PD-L1 staining using long-stored paraffin sections may not be consistent with the true PD-L1 expression of patients. Therefore, it is necessary to explore the expression of PD-L1(SP142) in paraffin sections of invasive breast cancer with different storage times and the optimal storage temperature for unstained paraffin sections. METHODS: The study included 71 cases of PD-L1(SP142) positive breast cancer. The unstained paraffin sections were stored at room temperature conditions (20-25 °C), 4 °C, -20 °C and - 80 °C, respectively. PD-L1 staining was performed at 1, 2, 3, 4, 8, 12 and 24 weeks of storage. PD-L1 expression was assessed with a continuity score. RESULTS: The PD-L1 antigen was gradually lost as the storage time of paraffin sections increased. The PD-L1 positivity rate was 97.18% at 1 week for the sections stored at room temperature, and decreased from 83.10 to 71.83% for the sections stored for 2 weeks to 4 weeks, and 61.97%, 54.93%, and 32.93% for 8, 12, and 24 weeks, respectively. When stored at low temperatures of 4 °C, -20 °C and - 80 °C, the positivity rate decreases with the same trend but more slowly compared to room temperature. The mean IC score of PD-L1 also showed a gradual decrease in all cases. In the consistency analysis, PD-L1 expression in slices stored at room temperature for 2 weeks was consistent with PD-L1 expression in fresh slices (ICC ≥ 0.9 for all slices), and PD-L1 expression in slices stored at 4 °C or -20 °C for 4 weeks was consistent with PD-L1 expression in fresh slices (ICC ≥ 0.9 for all slices). When stored under refrigeration at -80 °C, PD-L1 expression in slices stored for 3 weeks was consistent with that in fresh slices (ICC ≥ 0.9). CONCLUSIONS: To our knowledge, this is the first article on the effect of preservation time and preservation temperature of paraffin sections on PD-L1 expression in breast cancer. Long-term storage of paraffin sections of unstained invasive breast cancer can lead to antigen loss of PD-L1 (SP142). Refrigerated storage of paraffin sections can delay antigen loss, with best results at 4 °C or -20 °C, and a storage time of no more than 4 weeks is recommended.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Parafina , Antígeno B7-H1/metabolismo , Imuno-Histoquímica , Fatores de Tempo , Biomarcadores Tumorais/análise
20.
ACS Synth Biol ; 12(12): 3716-3729, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38052004

RESUMO

Riboswitches are noncoding RNA switches that are largely utilized in bacteria and play a significant role in synthetic biology. Nonetheless, their natural counterparts possess lengthy sequences and intricate structures, posing challenges for their modular integration into complex gene circuits. Consequently, it is imperative to develop simplified synthetic riboswitches that can be effortlessly incorporated into gene circuits. The conventional approach to generate synthetic riboswitches entails tedious library construction and extensive screening, which frequently yields suboptimal performance. To overcome this obstacle, alternative methods are urgently needed. In this study, we created a novel approach to designing a diverse set of transcription-activating riboswitches that exhibit high performance and broad compatibility. The strategy involved starting with a synthetic theophylline RNA aptamer and designing an expression platform that forms a transcriptional terminator in its inactive state but switches to an antiterminator when it is activated. Several sequences were designed, constructed, and subjected to virtual screening, resulting in the identification of two transcription-activating riboswitches. These riboswitches were then engineered to reduce the basal leakage and increase the activation level through extending the hairpin region using a screened random sequence. These architecturally minimal synthetic riboswitches were highly adapted to different constitutive promoters in a modular manner, generating a differentially responsive output to theophylline. As a proof-of-principle, the synthetic riboswitches were applied to rewire a synthetic quorum-sensing circuit (QSC). The reprogrammed QSC successfully modulated the temporal responsive profile against the activation. This strategy is expected to expand the variety of high-performance riboswitches that are responsive to different ligands, thereby further facilitating the design of complex genetic circuits.


Assuntos
Aptâmeros de Nucleotídeos , Riboswitch , Riboswitch/genética , Teofilina/farmacologia , Teofilina/metabolismo , Regiões Promotoras Genéticas/genética , Redes Reguladoras de Genes , Aptâmeros de Nucleotídeos/genética , Aptâmeros de Nucleotídeos/química
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