Cyano-Substituted Oligo(p-phenylene vinylene) Derivatives with Aggregation-Induced Enhanced Emissions and Mechanofluorochromic Luminescence.

Developing red fluorescence emitters with simple structures via convenient synthetic routes is highly desirable yet challenging. Herein, two novel donor-acceptor-type red emitters, DCFOPV-TPA and SCFOPV-TPA, featuring the intramolecular charge transfer effect were designed by integrating triphenylamine and trifluoromethyl into a CN-substituted oligo(p-phenylene vinylene) backbone. Both chromophores exhibited aggregation-induced enhanced emission and solvatochromic behavior. Moreover, DCFOPV-TPA also displayed reversible mechanofluorochromic properties under external force.

SelK promotes glioblastoma cell proliferation by inhibiting ß-TrCP1 mediated ubiquitin-dependent degradation of CDK4.

BACKGROUND: Glioblastoma (GB) is recognized as one of the most aggressive brain tumors, with a median survival of 14.6 months. However, there are still some patients whose survival time was greater than 3 years, and the biological reasons behind this clinical phenomenon arouse our research interests. By conducting proteomic analysis on tumor tissues obtained from GB patients who survived over 3 years compared to those who survived less than 1 year, we identified a significant upregulation of SelK in patients with shorter survival times. Therefore, we hypothesized that SelK may be an important indicator related to the occurrence and progression of GBM. METHODS: Proteomics and immunohistochemistry from GB patients were analyzed to investigate the correlation between SelK and clinical prognosis. Cellular phenotypes were evaluated by cell cycle analysis, cell viability assays, and xenograft models. Immunoblots and co-immunoprecipitation were conducted to verify SelK-mediated ubiquitin-dependent degradation of CDK4. RESULTS: SelK was found to be significantly upregulated in GB samples from short-term survivors (≤ 1 year) compared to those from long-term survivors (≥ 3 years), and its expression levels were negatively correlated with clinical prognosis. Knocking down of SelK expression reduced GB cell viability, induced G0/G1 phase arrest, and impaired the growth of transplanted glioma cells in nude mice. Down-regulation of SelK-induced ER stress leads to a reduction in the expression of SKP2 and an up-regulation of ß-TrCP1 expression. Up-regulation of ß-TrCP1, thereby accelerating the ubiquitin-dependent degradation of CDK4 and ultimately inhibiting the malignant proliferation of the GB cells. CONCLUSION: This study discovered a significant increase in SelK expression in GB patients with poor prognosis, revealing a negative correlation between SelK expression and patient outcomes. Further mechanistic investigations revealed that SelK enhances the proliferation of GB cells by targeting the endoplasmic reticulum stress/SKP2/ß-TrCP1/CDK4 axis.

High-efficiency color-tunable ultralong room-temperature phosphorescence from organic-inorganic metal halides via synergistic inter/intramolecular interactions.

Materials exhibiting highly efficient, ultralong and multicolor-tunable room-temperature phosphorescence (RTP) are of practical importance for emerging applications. However, these are still very scarce and remain a formidable challenge. Herein, using precise structure design, several novel organic-inorganic metal-halide hybrids with efficient and ultralong RTP have been developed based on an identical organic cation (A). The original organic salt (ACl) exhibits red RTP properties with low phosphorescence efficiency. However, after embedding metals into the organic salt, the changed crystal structure endows the resultant metal-halide hybrids with excellent RTP properties. In particular, A2ZnCl4·H2O exhibits the highest RTP efficiency of up to 56.56% with a long lifetime of up to 159 ms. It is found that multiple inter/intramolecular interactions and the strong heavy-atom effect of the rigid metal-halide hybrids can suppress molecular motion and promote the ISC process, resulting in highly stable and localized triplet excitons followed by highly efficient RTP. More crucially, multicolor-tunable fluorescence and RTP achieved by tuning the metal and halogen endow these materials with wide application prospects in the fields of multilevel information encryption and dynamic optical data storage. The findings promote the development of phosphorescent metal-halide hybrids for potential high-tech applications.

Chlorella pyrenoidosa polysaccharides supplementation increases Drosophila melanogaster longevity at high temperature.

Chlorella pyrenoidos polysaccharides (CPPs) are the main active components of Chlorella pyrenoidos. They possess beneficial health properties, such as antioxidant, anti-inflammatory, and immune-enhancing. This study aims to investigate the protective function and mechanism of CPPs against high-temperature stress injury. Results showed that supplementation with 20 mg/mL CPPs significantly extended the lifespan of Drosophila melanogaster under high-temperature stress, improved its motility, and enhanced its resistance to starvation and oxidative stress. These effects were mainly attributed to the activation of Nrf2 signaling and enhanced antioxidant capacity. Additionally, it has been discovered that CPPs supplementation enhanced Drosophila resilience by preventing the disruption of the intestinal barrier and accumulation of reactive oxygen species caused by heat stress. Overall, these studies suggest that CPPs could be a useful natural therapy for preventing heat stress-induced injury.

Embedding Te4+ into Sn4+-Based Metal Halide To Passivate Structure Defects for High-Performance Light-Emitting Application.

Low-dimensional lead-halide hybrids are an emerging class of optical functional material but suffer the problems of toxicity and poor air stability. Among lead-free metal halides, tin(IV)-based metal halides are promising optoelectronic materials due to their robust structure and environmental friendliness. However, their photoluminescence (PL) properties are poor, and the underlying mechanisms are still elusive. Herein, a stable Sn4+-based halide hybrid, (C4H7N2)2SnCl6, was developed, which however exhibits poor PL properties at room temperature (RT) due to the lattice defects and the robust crystal structure. To enhance its PL efficiency, the Te4+ ion with a stereoactive 5s2 lone pair has been introduced into the lattice. As a result, Te4+-doped (C4H7N2)2SnCl6 displays broadband orange emission (∼640 nm) with a PL efficiency of ∼46% at RT. Interestingly, Te4+-doped (C4H7N2)2SnCl6 shows triple emission bands at 80 K, which could be due to the synergistic effect of the organic cations and the self-trapped state induced by Te4+. Additionally, high-performance white light-emitting diodes were prepared using Te4+-doped (C4H7N2)2SnCl6, revealing the potential of this material for lighting applications. This study provides new insight into the PL mechanism of Sn4+-based metal-halide hybrids and thus facilitates the design and development of eco-friendly light-emitting metal halides.

Discovery of the 2,4-disubstituted quinazoline derivative as a novel neddylation inhibitor for tumor therapy.

Overactivation of neddylation has been found in a number of common human tumor-related diseases. In recent years, targeting the neddylation pathway has become an appealing anti-cancer strategy, and it is critical to find neddylation inhibitors with novel structures and higher efficacy. Here, we present the discovery of novel inhibitors of the NEDD8-activating enzyme (NAE) and their antitumor activity in vitro. All synthesized 1,4-disubstituted piperidine compounds were evaluated for antiproliferative activity against MGC-803, MCF-7, A549, and KYSE-30 cells. Among five representative compounds, III-26 bearing a quinazoline motif was identified as the lead one due to the fact that it significantly hindered the neddylation of Cullin1. Cellular mechanisms elucidated that III-26 inhibited the proliferation, migration, and invasion of UBC12-overexpressed MGC-803 cell lines, as well as induced apoptosis and arrested the cell cycle at G2/M phase. Importantly, III-26 reduced NAE activity, thus selectively preventing neddylation of Cullin3 and Cullin1 over other Cullin members. At a dose of 4 µM, III-26 virtually entirely blocked UBC12-NEDD8 conjugation in MGC-803 cells. Our molecular modeling and kinetic investigation suggested that this compound may function as a non-covalent inhibitor of NAE.

Seasonal drought promotes citrate accumulation in citrus fruit through the CsABF3-activated CsAN1-CsPH8 pathway.

Plenty of rainfall but unevenly seasonal distribution happens regularly in southern China. Seasonal drought from summer to early autumn leads to citrus fruit acidification, but how seasonal drought regulates citrate accumulation remains unknown. Herein, we employed a set of physiological, biochemical, and molecular approaches to reveal that CsABF3 responds to seasonal drought stress and modulates citrate accumulation in citrus fruits by directly regulating CsAN1 and CsPH8. Here, we demonstrated that irreversible acidification of citrus fruits is caused by drought lasting for > 30 d during the fruit enlargement stage. We investigated the transcriptome characteristics of fruits affected by drought and corroborated the pivotal roles of a bHLH transcription factor (CsAN1) and a P3A-ATPase gene (CsPH8) in regulating citrate accumulation in response to drought. Abscisic acid (ABA)-responsive element binding factor 3 (CsABF3) was upregulated by drought in an ABA-dependent manner. CsABF3 activated CsAN1 and CsPH8 expression by directly and specifically binding to the ABA-responsive elements (ABREs) in the promoters and positively regulated citrate accumulation. Taken together, this study sheds new light on the regulatory module ABA-CsABF3-CsAN1-CsPH8 responsible for citrate accumulation under drought stress, which advances our understanding of quality formation of citrus fruit.

Identification of novel benzothiazole derivatives as inhibitors of NEDDylation pathway to inhibit the progression of gastric cancer.

The overexpression of neddylation modification is frequently observed in human tumor cells. Targeting the neddylation pathway has been recognized as a promising anticancer therapeutic strategy, thus discovering potent and selective neddylation inhibitors is of great importance. In this study, we designed and synthesized a series of novel neddylation inhibitors bearing benzothiazole scaffolds by molecular hybridization strategy and all compounds were evaluated for antiproliferative activity against MGC-803, MCF-7, A549 and KYSE-30 cell lines. In vitro anti-tumor studies showed that the most promising compound X-10, effectively suppressed MGC-803 cells growth and migration, induced apoptosis and arrested cell cycle at G2/M phase. Importantly, by directly interacting with NAE1, X-10 blocked NAE1 activity, specifically preventing neddylation of Cullin 3 and Cullin 1, and produced a dose-response decline in the level of UBC12-NEDD8 complex. Overall, our data indicate that X-10 inhibits the process of neddylation, making it a potentially agent for both cancer prevention and therapy purposes.

[Analysis of ARID1B gene variant in a patient with mental retardation and ejaculatory dysfunction].

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a patient with mental retardation and ejaculatory dysfunction. METHODS: A patient with mental retardation and ejaculatory dysfunction who was admitted to the First Affiliated Hospital of Air Force Military Medical University on November 18, 2021 was selected as the study subject. Clinical data of the patient were collected. Peripheral venous blood samples were collected from the patient and his parents. Whole exome sequencing (WES) was carried out for the patient, and the candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The patient, a 26-year-old male, had manifested atypical mental retardation and ejaculatory dysfunction. WES revealed that he has harbored a heterozygous variant of the ARID1B gene, namely c.5776C>T (p.Arg1926X). Sanger sequencing verified that neither of his parents has carried the same variant. The variant has been recorded in the 1000 Genomes, ExAC, gnomAD and ClinVar databases. A search of the dbSNP database suggested that the variant has a population frequency of 0.000 4%. The variant was predicted as deleterious by online software including Mutation Taster, CADD, and MutPred. Analysis with Cluster Omega online software suggested that the amino acid encoded by the variant site was highly conserved among various species. Analysis with PyMOL software suggested that the variant may affect the function of the encoded protein. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and ClinGen, the variant was predicted to be pathogenic. CONCLUSION: The c.5776C>T (p.Arg1926X) variant of the ARID1B gene probably underlay the mental retardation and ejaculatory dysfunction in this patient. Above finding has broadened the spectrum of the ARID1B gene variants and provided reference for the diagnosis and treatment of the patient.

CRTAC1 enhances the chemosensitivity of non-small cell lung cancer to cisplatin by eliciting RyR-mediated calcium release and inhibiting Akt1 expression.

Sensitivity to platinum-based combination chemotherapy is associated with a favorable prognosis in patients with non-small cell lung cancer (NSCLC). Here, our results obtained from analyses of the Gene Expression Omnibus database of NSCLC patients showed that cartilage acidic protein 1 (CRTAC1) plays a role in the response to platinum-based chemotherapy. Overexpression of CRTAC1 increased sensitivity to cisplatin in vitro, whereas knockdown of CRTAC1 decreased chemosensitivity of NSCLC cells. In vivo mouse experiments showed that CRTAC1 overexpression increased the antitumor effects of cisplatin. CRTAC1 overexpression promoted NFAT transcriptional activation by increasing intracellular Ca2+ levels, thereby inducing its regulated STUB1 mRNA transcription and protein expression, accelerating Akt1 protein degradation and, in turn, enhancing cisplatin-induced apoptosis. Taken together, the present results indicate that CRTAC1 overexpression increases the chemosensitivity of NSCLC to cisplatin treatment by inducing Ca2+-dependent Akt1 degradation and apoptosis, suggesting the potential of CRTAC1 as a biomarker for predicting cisplatin chemosensitivity. Our results further reveal that modulating the expression of CRTAC1 could be a new strategy for increasing the efficacy of cisplatin in chemotherapy of NSCLC patients.

FRET cascade miRNA addition probe from non-crosstalk DNA photonic wire assisted with clustering algorithm for early diagnosis of acute myocardial infarction.

Early and accurate diagnosis of acute myocardial infarction (AMI) can significantly reduce patient mortality. A variety of miRNAs are found to dysregulate in AMI patients, but the up- or down-regulation of a specific miRNA may not be evident in the early stage, making it difficult to achieve accurate diagnosis. Here, proposing the design that DNA photonic wire (PW) with no spectral crosstalk would make an excellent template for miRNA conjoint analysis, we report the construction of a miRNA addition probe for the additive analysis of two up-regulated miRNAs (miR-133a and miR-208a) for early diagnosis of AMI in clinical serum samples. A three-dye non-crosstalk DNA PW is built to form the two-step fluorescence resonance energy transfer (FRET) cascade system, in which three paths can blocking the FRET cascade for separate or additive analysis of the two miRNAs. K-Means clustering algorithm is further utilized to classify the output signals of the miRNA addition probe, achieving a 100% accurate diagnosis of early AMI in both the training (n = 40) and validation (n = 19) cohorts of clinical serum samples.

Nomograms and scoring system for forecasting overall and cancer-specific survival of patients with prostate cancer.

BACKGROUND: Estimated life expectancy is one of the most important factors in determining treatment options for prostate cancer (PCa) patients. However, clinicians have few effective prognostic tools to individually assess survival in patients with PCa. METHODS: We screened 283,252 patients diagnosed with PCa from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015, and randomly divided them into the training and validation groups. We used univariate and multivariate Cox analyses to identify independent prognostic factors and further established nomograms to predict 1-, 3-, 5-, and 10-year overall survival (OS) and cancer-specific survival (CSS) for PCa patients. The prediction performance of nomograms was tested and externally validated by Concordance index (C-index) and receiver operating characteristic (ROC) curve. Calibration curve and decision curve analysis (DCA) were used for internal validation. We further developed PCa prognostic scoring system based on the impact of available variables on survival. RESULTS: The variables age, race, marital status, TNM stage, surgery method, radiotherapy, chemotherapy, PSA value, and Gleason score identified as independent prognostic factors were included in the survival nomograms. The results of training (C-index: OS = 0.776, CSS = 0.889; AUC value: OS = 0.772-0.802, CSS = 0.892-0.936) and external validation (C-index: OS = 0.759, CSS = 0.875) indicated our nomograms had good performance in predicting 1-, 3-, 5-, and 10-year OS and CSS prediction. Internal validation using the calibration curves and DCA curves demonstrated the effectiveness of the prediction models. The prognostic scoring system was more effective than the AJCC staging system in predicting the survival of PCa patients, especially for OS. CONCLUSION: The prognostic nomograms and prognostic scoring system have favorable performance in predicting OS and CSS of PCa patients. These individualized survival prediction tools may contribute to clinical decisions.

Effects of Fertilization Approaches on Plant Development and Fertilizer Use of Citrus.

Fertilization is an important part of citrus crop management. However, limited details are available about the fertilization approach on citrus plant development. A pot experiment for the fertilization approaches and fertigation levels were conducted in this study. Four fertilization approaches, namely, drip fertigation (DF), broadcast fertilization (CK+), hole fertilization (HF) and pour fertilization (PF) were tested. The fertigation level treatment included 100% (DF-337.5), 80% (DF-270), 60% (DF-202.5) and 40% (DF-135) fertilizer supply with DF, and the 100% fertilizer supply with broadcast fertilization were served as control (CK). The results showed that DF not only increased the absorptions of nitrogen (N), phosphorus (P) and potassium (K) but also promoted citrus plant height, stem diameter and dry weight. In fruit quality, DF had the highest fruit total soluble solid (TSS) and titratable acidity (TA) contents. For fertilizer loss, DF had the lowest N and K leaching losses of 9.26% and 4.05%, respectively, and the lowest N and K runoff losses among the approaches. Isotopic tracing with 15N indicated that DF had the highest fertilizer use efficiency. Based on the analysis of fertigation levels, DF approach with 60% fertilizer reduction could improve citrus plant development. Therefore, DF promoted citrus plant growth and fruit quality by accelerating fertilizer utilization and impairing fertilizer loss. The fertilizer amount in citrus production could be reduced significantly using DF.

Influence of revegetation on soil microbial community and its assembly process in the open-pit mining area of the Loess Plateau, China.

Vegetation recovery is an important marker of ecosystem health in the mining area. Clarifying the influence of vegetation recovery on the characteristics of soil microbial community and its assembly process can improve our understanding of the ecological resilience and self-maintaining mechanism in the open-pit mining area. For this purpose, we employed MiSeq high-throughput sequencing coupled with null model analysis to determine the composition, molecular ecological network characteristics, key bacterial and fungal clusters, and the assembly mechanism of the soil microbial communities in shrubs (BL), coniferous forest (CF), broad-leaved forests (BF), mixed forest (MF), and the control plot (CK, the poplar plantation nearby that had been continuously grown for over 30 a without disturbance). The results showed that the vegetation restoration model had a significant influence on the α-diversity of the microbial community (p < 0.05). Compared with CK, Sobs and Shannon index of MF and CF have increased by 35.29, 3.50, and 25.18%, 1.05%, respectively, whereas there was no significant difference in the α-diversity of fungal community among different vegetation restoration types, Actinobacteria, Chloroflexi, Proteobacteria, and Acidobacteria were the dominant phyla. The diversity of the first two phyla was significantly higher than those of CK. However, the diversity of the last two phyla was dramatically lower than those of CK (p < 0.05). Ascomycota and Basidiomycota were dominant phyla in the fungal community. The abundance and diversity of Ascomycota were significantly higher than those of CK, while the abundance and diversity of the latter were considerably lower than those of CK (p < 0.05). The stochastic process governed the assembly of the soil microbial community, and the contribution rate to the bacterial community construction of CK, CF, BF, and MF was 100.0%. Except for MF, where the soil fungal community assembly was governed by the deterministic process, all other fungal communities were governed by the stochastic process. Proteobacteria and Acidobacteria are key taxa of the bacterial network, while Mortierellales, Thelebolales, Chaetothyriales, and Hypocreales are the key taxa of the fungal network. All these results might provide the theoretical foundation for restoring the fragile ecosystem in the global mining region.

A predictive model based on ground glass nodule features via high-resolution CT for identifying invasiveness of lung adenocarcinoma.

Objective: The morphology of ground-glass nodule (GGN) under high-resolution computed tomography (HRCT) has been suggested to indicate different histological subtypes of lung adenocarcinoma (LUAD); however, existing studies only include the limited number of GGN characteristics, which lacks a systematic model for predicting invasive LUAD. This study aimed to construct a predictive model based on GGN features under HRCT for LUAD. Methods: A total of 301 surgical LUAD patients with HRCT-confirmed GGN were enrolled, and their GGN-related features were assessed by 2 individual radiologists. The pathological diagnosis of the invasive LUAD was established by pathologic examination following surgery (including 171 invasive and 130 non-invasive LUAD patients). Results: GGN features including shorter distance from pleura, larger diameter, area and mean CT attenuation, more heterogeneous uniformity of density, irregular shape, coarse margin, not defined nodule-lung interface, spiculation, pleural indentation, air bronchogram, vacuole sign, vessel changes, lobulation were observed in invasive LUAD patients compared with non-invasive LUAD patients. After adjustment by multivariate logistic regression model, GGN diameter (OR = 1.490, 95% CI, 1.326-1.674), mean CT attenuation (OR = 1.007, 95% CI, 1.004-1.011) and heterogeneous uniformity of density (OR = 3.009, 95% CI, 1.485-6.094) were independent risk factors for invasive LUAD. In addition, a predictive model integrating these three independent GGN features was established (named as invasion of lung adenocarcinoma by GGN features (ILAG)), and receiver-operating characteristic curve illustrated that the ILAG model presented good predictive value for invasive LUAD (AUC: 0.919, 95% CI, 0.889-0.949). Conclusions: ILAG predictive model integrating GGN diameter, mean CT attenuation and heterogeneous uniformity of density via HRCT shows great potential for early estimation of LUAD invasiveness.

Optimal Modeling and Simulation of the Relationship between Athletes' High-Intensity Training and Sports Injuries.

In order to take into account the physical health of athletes and the quality of sports training, an optimization modeling and simulation method for the relationship between high-intensity training and sports injuries of athletes is proposed. The research of the specific content of the method is based on the two-dimensional and three-dimensional registration principles. In the research process, the program is written strictly according to the registration principle, and the correctness of the method is effectively tested by means of experimental methods. Digital image reconstruction measures based on 3D models may be based on ray tracing methods. The experimental results show that the number of accurate cases of this method is 77, and the accuracy rate is 96.3%. The proposed method can formulate a scientific and effective injury prevention strategy for athletes during high-intensity training.

A highly-efficient 3D DNAzyme motor for sensitive biosensing analysis.

Herein, driven by the need of highly-efficient DNAzyme-amplified detection strategy, a novel 3D DNAzyme motor was designed as a biosensor platform for realizing sensitive detection of target DNA. The 3D DNAzyme motor was composed of target-activated DNAzyme nanowires and substrates H1-Fc that co-immobilized on Au@Fe3O4 nanoparticles (Au@Fe3O4NPS) surface, possessing high local concentration of DNA reactants and shortened distance between DNAzyme and substrates for enhancing electrochemical signal. Compared with traditional DNAzyme-powered machines, the target-activated DNAzyme nanowires of 3D DNAzyme motor had greater flexibility and more powerful cleavage capability without troublesome sequence optimization, which overcame the space limitation and simultaneously interacted with adjacent and distant substrates H1-Fc to output a large amount of cleavage products with high signal response. Therefore, on account of the above-mentioned merits of nanoparticles localization DNA design and DNAzyme nanowires, the reported 3D DNAzyme motor ingeniously overcame many defects existing in traditional DNAzyme-amplified detection strategies such as low reactants concentration, limited flexibility of DNAzyme and small DNAzyme swing range, realizing the sensitive detection of target DNA with a detection limit of 1.7 fM ranging from 5 fM to 50 nM. Impressively, the 3D DNAzyme motor here presented a new strategy to achieve effective DNAzyme signal amplification and provided a reference for the assembly of various and functional 3D DNA machines in the future.

mTOR pathway gene mutations predict response to immune checkpoint inhibitors in multiple cancers.

BACKGROUND: mTOR pathway is known to promote cancer malignancy and influence cancer immunity but is unknown for its role in immune checkpoint inhibitors (ICI) therapy. METHODS: Using Memorial Sloan-Kettering Cancer Center dataset (MSKCC), we extracted mTOR pathway gene mutations for stepwise Cox regression in 1661 cancer patients received ICI. We associated the mutation of the gene signature resulted from the stepwise Cox regression with the 1661 patients' survival. Other 553 ICI-treated patients were collected from 6 cohorts for validation. We also performed this survival association in patients without ICI treatment from MSKCC as discovery (n = 2244) and The Cancer Genome Atlas (TCGA) as validation (n = 763). Pathway enrichment analysis were performed using transcriptome profiles from TCGA and IMvigor210 trial to investigate the potential mechanism. RESULTS: We identified 8 genes involved in mTOR pathway, including FGFR2, PIK3C3, FGFR4, FGFR1, FGF3, AKT1, mTOR, and RPTOR, resulted from stepwise Cox regression in discovery (n = 1661). In both discovery (n = 1661) and validation (n = 553), the mutation of the 8-gene signature was associated with better survival of the patients treated with ICI, which was independent of tumor mutation burden (TMB) and mainly attributed to the missense mutations. This survival association was not observed in patients without ICI therapy. Intriguingly, the mutation of the 8-gene signature was associated with increased TMB and PD1/PD-L1 expression. Immunologically, pathways involved in anti-tumor immune response were enriched in presence of this mutational signature in mTOR pathway, leading to increased infiltration of immune effector cells (e.g., CD8 + T cells, NK cells, and M1 macrophages), but decreased infiltration of immune inhibitory M2 macrophages. CONCLUSIONS: These results suggested that mTOR pathway gene mutations were predictive of better survival upon ICI treatment in multiple cancers, likely by its association with enhanced anti-tumor immunity. Larger studies are warranted to validate our findings.

Tetrahedral DNA Nanostructure with Multiple Target-Recognition Domains for Ultrasensitive Electrochemical Detection of Mucin 1.

In this work, a tetrahedral DNA nanostructure (TDN) designed with multiple biomolecular recognition domains (m-TDN) was assembled to construct an ultrasensitive electrochemical biosensor for the quantitative detection of tumor-associated mucin 1 (MUC-1) protein. This new nanostructure not only effectively increased the capture efficiency of target proteins compared to the traditional TDN with a single recognition domain but also enhanced the sensitivity of the constructed electrochemical biosensors. Once the target MUC-1 was captured by the protein aptamers, the ferrocene-marked DNA strands as electrochemical signal probes at the vertices of m-TDN would be released away from the electrode surface, causing significant reduction of the electrochemical signal, thereby enhancing significantly the detection sensitivity. As a result, this well-designed biosensor achieved ultrasensitive detection of the biomolecule at a linear range from 1 fg mL-1 to 1 ng mL-1, with the limit of detection down to 0.31 fg mL-1. This strategy provides a new approach to enhance the detection sensitivity for the diagnosis of diseases.