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PURPOSE: To assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) of gemcitabine and oxaliplatin (GEMOX) plus systemic gemcitabine chemotherapy (GEM-SYS) in combination with lenvatinib and programmed cell death protein-1 (PD-1) inhibitor for patients with large unresectable intrahepatic cholangiocarcinoma (uICC). METHODS: From November 2019 to December 2022, 21 large uICC patients who underwent GEMOX-HAIC (Day 1) and GEM-SYS (Day 8) (3w/cycle) combined with lenvatinib and PD-1 inhibitor were retrospectively enrolled. Local tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were analyzed. Tumor response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. AEs were evaluated by the common terminology criteria for adverse events (CTCAE) version 5.0. RESULTS: After a median follow-up duration of 16.0 months (range 5-43.5 months), 17 patients had died. The median OS was 19.5 months (range 9-43.5 months), and the median PFS was 6.0 months (range 2.5-38.5 months). The 1-, 2-, and 3-year OS rates were 71.4 %, 42.9 %, and 19.0 %, respectively. The 1-, 2-, and 3-year PFS rates were 33.3 %, 19.0 %, and 9.5 %, respectively. Complete response, partial response, stable disease, and progressive disease were observed in 0 (0 %), 11 (52.3 %), 5 (23.8 %), and 5 (23.8 %) patients, respectively. The disease control rate and objective response rate were 76.1 % and 52.3 %, respectively. None of the enrolled patients experienced grade 5 AEs. CONCLUSIONS: GEMOX-HAIC plus GEM-SYS in combination with lenvatinib and PD-1 inhibitor was effective and well tolerated for patients with large uICC.
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Spiral inorganic perovskite nanowires (NWs) possess unique morphologies and properties that allow them highly attractive for applications in optoelectronic and catalytic fields. In popular solution-based synthesis methodology, however, challenges persist in simultaneously achieving precise and facile control over morphological twisting and fantastic carrier lifetimes. Here, a cooperative strategy of concurrently employing selective etching and ligand engineering is applied to facilitate the formation of spiral CsPbBr3 perovskite NWs with an ultralong carrier lifetime of ≈2 µs. Specifically, a novel amine of 1-(p-tolyl)ethanamine is introduced to functionalize as both a selective etchant and the source of forming an effective ligand to passivate the exposed facets, favoring the structural twisting and the enhancement of carrier lifetimes. The twisting behaviors are dependent on the etch ratios, which are essentially associated with the densities of grain boundaries and dislocations in the NWs. The ultralong carrier lifetime and long-term stability of the spiral NWs open up new possibilities for all-inorganic perovskites in optoelectronic and photocatalytic fields, while the cooperative synthesis strategy paves the way for exploring complex spiral structures with tunable morphology and functionality.
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Polymer electrolyte fuel cells are an essential technology for future local emission-free mobility. One of the critical challenges for thriving commercialization is water management in the cells. We propose small- and wide-angle X-ray scattering as a suitable diagnostic tool to quantify the liquid saturation in the catalyst layer and determine the hydration of the ion-conducting membrane in real operating conditions. The challenges that may occur in operando data collection are described in detailâseparation of the anode and cathode, cell alignment to the beam, X-ray radiation damage, and the possibility of membrane swelling. A synergistic development of experimental setup, data acquisition, and data interpretation circumvents the major challenges and leads to practical and reliable insights.
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Ligand engineering is crucial for tuning the structural and optoelectronic properties of perovskite nanocrystals (NCs), which also improves their stability. In contrast to the typically used long-chain alkylamine ligands, we successfully introduced an aromatic 1-(p-tolyl)ethylamine (PTEA) ligand to synthesize the CsPbX3 (X = Br or I) NCs. The CsPbI3 and CsPbBr3 NCs demonstrated long carrier lifetimes of â¼877 and 49 ns, respectively, as well as high photoluminescence quantum yields (PLQYs) of â¼99% and 95%, respectively. Furthermore, such NCs realized excellent long-term stability in an ambient atmosphere without obvious degradation over one month. All of these properties were better than the properties of NCs coated with the conventional alkylamine ligands. The high performance of these NCs was discussed with the effective surface passivation by PTEA. Our finding suggests a facile and effective ligand (PTEA) for modulating perovskites, achieving enhancement of both the carrier lifetime and the PLQY.
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OBJECTIVE: To compare the outcomes between a modified Retzius-sparing robot-assisted radical prostatectomy (mRS-RARP) technique and conventional robot-assisted radical prostatectomy (Con-RARP) technique for cases with anterior prostate cancer (PCa), especially positive surgical margin (PSM) rates and urinary continence (UC). PATIENTS AND METHODS: We retrospectively included 193 mRS-RARP and 473 Con-RARP consecutively performed by a single surgeon for anterior PCa. Perioperative complications, pathology, and continence were compared after propensity score matching using 9 variables. RESULTS: After matching (n = 193 per group), PSM were not significantly different in the two groups (16.1% in mRS-RARP group vs. 15.0% in Con-RARP group, p = 0.779). The UC at catheter removal and at 1-month was significantly higher in the mRS-RARP (24.9% vs. 9.8%, p < 0.001; 29.0% vs. 13.5%, p < 0.001, respectively), but not at 3-, 6-, and 12-month follow-ups (p = 0.261, 0.832, and 0.683, respectively). CONCLUSION: mRS-RARP seems to be an oncologically safe approach for patients with anterior PCa. Compared with the conventional approach, mRS-RARP approach shows benefits in the short-term postoperative UC recovery.
Subject(s)
Prostatic Neoplasms , Robotic Surgical Procedures , Robotics , Male , Humans , Retrospective Studies , Propensity Score , Prostatectomy/methods , Robotic Surgical Procedures/methods , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Treatment OutcomeABSTRACT
Background: The application of chimeric antigen receptor (CAR) NK cells in solid tumors is hindered by lack of tumor-specific targets and inefficient CAR-NK cell efficacy. Claudin-6 (CLDN6) has been reported to be overexpressed in ovarian cancer and may be an attractive target for CAR-NK cells immunotherapy. However, the feasibility of using anti-CLDN6 CAR-NK cells to treat ovarian cancer remains to be explored. Methods: CLDN6 expression in primary human ovarian cancer, normal tissues and cell lines were detected by immunohistochemistry and western blot. Two types of third-generation CAR NK-92MI cells targeting CLDN6, CLDN6-CAR1 NK-92MI cells with domains containing self-activated elements (NKG2D, 2B4) and CLDN6-CAR2 NK-92MI cells with classical domains (CD28, 4-1BB) were constructed by lentivirus transfection, sorted by flow cytometry and verified by western blot and qPCR. OVCAR-3, SK-OV-3, A2780, Hey and PC-3 cells expressing the GFP and luciferase genes were transduced. Subcutaneous and intraperitoneal tumor models were established via NSG mice. The ability of CLDN6-CAR NK cells to kill CLDN6-positive ovarian cancer cells were evaluated in vitro and in vivo by live cell imaging and bioluminescence imaging. Results: Both CLDN6-CAR1 and CLDN6-CAR2 NK-92MI cells could specifically killed CLDN6-positive ovarian cancer cells (OVCAR-3, SK-OV-3, A2780 and Hey), rather than CLDN6 negative cell (PC-3), in vitro. CLDN6-CAR1 NK-92MI cells with domains containing self-activated elements (NKG2D, 2B4) exhibited stronger cytotoxicity than CLDN6-CAR2 NK-92MI cells with classical domains (CD28, 4-1BB). Furthermore, CLDN6-CAR1 NK cells could effectively eliminate ovarian cancer cells in subcutaneous and intraperitoneal tumor models. More importantly, CAR-NK cells combined with immune checkpoint inhibitors, anti-PD-L1, could synergistically enhance the antitumor efficacy of CLDN6-targeted CAR-NK cells. Conclusions: These results indicate that CLDN6-CAR NK cells possess strong antitumor activity and represent a promising immunotherapeutic modality for ovarian cancer.
Subject(s)
Claudins , Ovarian Neoplasms , Receptors, Chimeric Antigen , Humans , Animals , Mice , Female , Receptors, Chimeric Antigen/genetics , Ovarian Neoplasms/therapy , Ovarian Neoplasms/metabolism , Cell Line, Tumor , Apoptosis , NK Cell Lectin-Like Receptor Subfamily K/metabolism , CD28 Antigens/metabolism , Killer Cells, Natural , Immunotherapy/methods , Immunotherapy, Adoptive/methodsABSTRACT
Hepatocellular carcinoma (HCC) is one of the most common malignancies and the third leading cause of cancer-related deaths globally. Hepatic arterial infusion chemotherapy (HAIC) treatment is widely accepted as one of the alternative therapeutic modalities for HCC owing to its local control effect and low systemic toxicity. Nevertheless, although accumulating high-quality evidence has displayed the superior survival advantages of HAIC of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) compared with standard first-line treatment in different scenarios, the lack of standardization for HAIC procedure and remained controversy limited the proper and safe performance of HAIC treatment in HCC. Therefore, an expert consensus conference was held on March 2023 in Guangzhou, China to review current practices regarding HAIC treatment in patients with HCC and develop widely accepted statements and recommendations. In this article, the latest evidence of HAIC was systematically summarized and the final 22 expert recommendations were proposed, which incorporate the assessment of candidates for HAIC treatment, procedural technique details, therapeutic outcomes, the HAIC-related complications and corresponding treatments, and therapeutic scheme management.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Treatment Outcome , Hepatic Artery/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fluorouracil/therapeutic use , Infusions, Intra-ArterialABSTRACT
Single cell sequencing is useful for resolving complex systems into their composite cell types and computationally mining them for unique features that are masked in pooled sequencing. However, while commercial instruments have made single cell analysis widespread for mammalian cells, analogous tools for microbes are limited. Here, we present EASi-seq (Easily Accessible Single microbe sequencing). By adapting the single cell workflow of the commercial Mission Bio Tapestri instrument, this method allows for efficient sequencing of individual microbes' genomes. EASi-seq allows thousands of microbes to be sequenced per run and, as we show, can generate detailed atlases of human and environmental microbiomes. The ability to capture large shotgun genome datasets from thousands of single microbes provides new opportunities in discovering and analyzing species subpopulations. To facilitate this, we develop a companion bioinformatic pipeline that clusters microbes by similarity, improving whole genome assembly, strain identification, taxonomic classification, and gene annotation. In addition, we demonstrate integration of metagenomic contigs with the EASi-seq datasets to reduce capture bias and increase coverage. Overall, EASi-seq enables high quality single cell genomic data for microbiome samples using an accessible workflow that can be run on a commercially available platform.
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BACKGROUND: Although partial nephrectomy has become the gold standard for T1 renal tumors whenever technically feasible, simple enucleation has shown superior results. To the best of our knowledge, no randomized controlled trials comparing these two surgical approaches have been published. OBJECTIVE: To compare the surgical margin status for robot-assisted simple enucleation (RASE) and standard robot-assisted partial nephrectomy (sRAPN) for clinical T1 renal tumors. DESIGN, SETTING, AND PARTICIPANTS: This is a prospective, randomized, controlled, noninferiority trial. A total of 380 patients aged 18-80 yr with newly diagnosed, sporadic, unilateral clinical T1 renal tumors (RENAL score <10) were enrolled and randomized to RASE or sRAPN. The primary endpoint was the positive surgical margin (PSM) rate, with a noninferiority margin of 7.5% set. The study was registered on ClinicalTrials.gov (NCT03624673). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We defined noninferiority for RASE versus standard RAPN as an upper 95% confidence interval (CI) bound of <7.5% for the difference in the proportion of patients with a PSM. RESULTS AND LIMITATIONS: A cohort of 380 patients was enrolled and randomly assigned to RASE (n = 190) or sRAPN (n = 190). On intention-to-treat analysis for patients with malignant tumors, 2.3% of patients in the RASE group and 3.0% in the sRAPN group had a PSM. The RASE group showed noninferiority to the sRAPN group within a 7.5% margin (difference -0.7%, 95% CI -4.0% to 2.7%). Per-protocol analysis also demonstrated noninferiority of RASE. The RASE group had a shorter median operative time (145 vs 155 min; p = 0.018) and a lower rate of tumor bed suturing (8.9% vs 43%; p < 0.001) in comparison to the sRAPN group. Estimated blood loss was considerably lower in the sRAPN group than in the RASE group (p = 0.046). The rate of recurrence did not differ between the groups (p > 0.9). CONCLUSIONS: RASE for the management of low- to intermediate-complexity tumors is noninferior to sRAPN in terms of the PSM rate. Long-term follow-up is needed to draw conclusions regarding oncological outcomes. PATIENT SUMMARY: We carried out a trial to compare simple tumor enucleation versus partial nephrectomy for renal tumors. The outcome we assessed was the proportion of patients with a positive surgical margin. Our results show that simple tumor enucleation is not inferior to partial nephrectomy for this outcome. Longer follow-up is needed to assess other cancer control outcomes.
Subject(s)
Kidney Neoplasms , Robotics , Humans , Margins of Excision , Prospective Studies , Treatment Outcome , Retrospective Studies , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Nephrectomy/methodsABSTRACT
Backward stimulated Brillouin scattering (SBS) in optical microcavities has been widely used in nonlinear optics and microwave photonics. Compared with glass material microcavity, magnesium fluoride crystal microcavity has the advantages of small absorption coefficient, fewer defects and larger nonlinear coefficient, moreover, it usually has a narrow gain bandwidth of tens of megahertz. Here, we design a high precision machining system to produce ultra-smooth surface magnesium fluoride crystal disk cavities with a diameter of about 5 mm, Q value exceeding 108, FSR matching material Brillouin gain. By simply modulating the pump wavelength and coupling power, we observe SBS phenomena with a 13.47â GHz Brillouin frequency shift near 1.55µm and cascaded stimulated Brillouin lasers (SBL) of up to 12 orders. In addition, the Brillouin-Kerr optical frequency comb in this device is demonstrated, observing nearly 300 comb lines spanning across a spectral window of 250â nm. Our research provides a way to fabricate high-Q crystal microcavities and demonstrates the potential of these devices in applications such as microwave sources and nonlinear optics.
ABSTRACT
Single cell sequencing is useful for resolving complex systems into their composite cell types and computationally mining them for unique features that are masked in pooled sequencing. However, while commercial instruments have made single cell analysis widespread for mammalian cells, analogous tools for microbes are limited. Here, we present EASi-seq (Easily Accessible Single microbe sequencing). By adapting the single cell workflow of the commercial Mission Bio Tapestri instrument, this method allows for efficient sequencing of individual microbes' genomes. EASi-seq allows thousands of microbes to be sequenced per run and, as we show, can generate detailed atlases of human and environmental microbiomes. The ability to capture large shotgun genome datasets from thousands of single microbes provides new opportunities in discovering and analyzing species subpopulations. To facilitate this, we develop a companion bioinformatic pipeline that clusters microbes by similarity, improving whole genome assembly, strain identification, taxonomic classification, and gene annotation. In addition, we demonstrate integration of metagenomic contigs with the EASi-seq datasets to reduce capture bias and increase coverage. Overall, EASi-seq enables high quality single cell genomic data for microbiome samples using an accessible workflow that can be run on a commercially available platform.
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Whole-genome duplication (WGD) leads to the duplication of both coding and non-coding sequences within an organism's genome, providing an abundant supply of genetic material that can drive evolution, ultimately contributing to plant adaptation and speciation. Although non-coding sequences contain numerous regulatory elements, they have been understudied compared to coding sequences. In order to address this gap, we explored the evolutionary patterns of regulatory sequences, coding sequences and transcriptomes using conserved non-coding elements (CNEs) as regulatory element proxies following the recent WGD event in opium poppy (Papaver somniferum). Our results showed similar evolutionary patterns in subgenomes of regulatory and coding sequences. Specifically, the biased or unbiased retention of coding sequences reflected the same pattern as retention levels in regulatory sequences. Further, the divergence of gene expression patterns mediated by regulatory element variations occurred at a more rapid pace than that of gene coding sequences. However, gene losses were purportedly dependent on relaxed selection pressure in coding sequences. Specifically, the rapid evolution of tissue-specific benzylisoquinoline alkaloid production in P. somniferum was associated with regulatory element changes. The origin of a novel stem-specific ACR, which utilized ancestral cis-elements as templates, is likely to be linked to the evolutionary trajectory behind the transition of the PSMT1-CYP719A21 cluster from high levels of expression solely in P. rhoeas root tissue to its elevated expression in P. somniferum stem tissue. Our findings demonstrate that rapid regulatory element evolution can contribute to the emergence of new phenotypes and provide valuable insights into the high evolvability of regulatory elements.
Subject(s)
Papaver , Papaver/genetics , Papaver/metabolism , Gene Duplication , Genome , Evolution, MolecularABSTRACT
PURPOSE: To evaluate the Epstein criteria for insignificant prostate cancer (CaP) prediction in a contemporary Chinese population, and to develop a risk model with combined clinical and systematic biopsy and targeted biopsy parameters for active surveillance. METHODS: A total of 249 CaP patients with biopsy Gleason score (GS) of 6 were included. One hundred and one patients were eligible for insignificant CaP on final pathology (GS ≤6 and organ-confined). Diagnostic tests were used to validate the ability of the 2 Epstein criteria. Univariate and multivariate regression analyses were performed to identify predictors of insignificant CaP for the development of predictive models. Receiver operating characteristics analysis was used to select the best model, followed by risk nomogram construction and internal validation. RESULTS: There were 47 patients met EC1 and 61 met EC2, with pathological upgrading rates of 36% and 41%, respectively, and 70% (71/101) and 64% (65/101) were missed, with areas under the curve of 0.591 and 0.594, respectively. Four prediction models were developed using regression analysis, and model 2 incorporating age, prostate-specific antigen density, maximum percentage of core involvement at systematic biopsy, and percentage of positive cores at targeted biopsy showed the best diagnostic value (area under the curveâ¯=â¯0.731, sensitivity 62.4%, specificity 77.0%) and was used to construct the nomogram. Calibration curves and decision curve analysis demonstrated favorable calibration (mean absolute error 0.048) and clinical benefits of the novel nomogram. CONCLUSION: The Epstein criteria need to be revised by incorporating targeted biopsy parameters to improve diagnostic performance, and a novel nomogram was developed with better prediction of insignificant CaP.
Subject(s)
East Asian People , Nomograms , Prostatic Neoplasms , Risk Assessment , Watchful Waiting , Humans , Male , Asian People , Biopsy , China , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/pathologyABSTRACT
CD8+ invariant natural killer T (iNKT) cells are functionally different from other iNKT cells and are enriched in human but not in mouse. To date, their developmental pathway and molecular basis for fate decision remain unclear. Here, we report enrichment of CD8+ iNKT cells in neonatal mice due to their more rapid maturation kinetics than CD8- iNKT cells. Along developmental trajectories, CD8+ and CD8- iNKT cells separate at stage 0, following stage 0 double-positive iNKT cells, and differ in HIVEP3 expression. HIVEP3 is lowly expressed in stage 0 CD8+ iNKT cells and negatively controls their development, whereas it is highly expressed in stage 0 CD8- iNKT cells and positively controls their development. Despite no effect on IFN-γ, HIVEP3 inhibits granzyme B but promotes interleukin-4 production in CD8+ iNKT cells. Together, we reveal that, as a negative regulator for CD8+ iNKT fate decision, low expression of HIVEP3 in stage 0 CD8+ iNKT cells favors their development and T helper 1-biased cytokine responses as well as high cytotoxicity.
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Objective: The study aimed to compare the efficacy and safety of androgen deprivation therapy (ADT) with abiraterone or docetaxel versus ADT alone as neoadjuvant therapy in patients with very-high-risk localized prostate cancer. Methods: This was a pooled analysis of two single-center, randomized, controlled, phase II clinical trials (ClinicalTrials.gov: NCT04356430 and NCT04869371) conducted from December 2018 to March 2021. Eligible participants were randomly assigned to the intervention (ADT plus abiraterone or docetaxel) and control (ADT alone) groups at a 2:1 ratio. Efficacy was evaluated by pathological complete response (pCR), minimal residual disease (MRD), and 3-year biochemical progression-free survival (bPFS). Safety was also analyzed. Results: The study included 42 participants in the ADT group, 47 in the ADT plus docetaxel group, and 48 in the ADT plus abiraterone group. A total of 132 (96.4%) participants had very-high-risk prostate cancer, and 108 (78.8%) had locally advanced disease. The ADT plus docetaxel group (28%) and ADT plus abiraterone group (31%) had higher rates of pCR or MRD (p = 0.001 and p < 0.001) compared with the ADT group (2%). The 3-year bPFS was 41.9% (95% CI: 26.6-57.2), 51.1% (95% CI: 36.8-65.4), and 61.2% (95% CI: 45.5-76.9), respectively. Significant difference was found among groups in terms of bPFS (p = 0.037). Conclusion: Compared with ADT alone, neoadjuvant therapy with ADT plus docetaxel or abiraterone could achieve better pathological outcomes (pCR or MRD) for very-high-risk localized prostate cancer. The ADT plus abiraterone group showed longer bPFS than ADT alone. The combination regimens were tolerable.
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Renal dysfunction is a common complication of sepsis. Early diagnosis and prompt treatment of sepsis with renal insufficiency are crucial for improving patient outcomes. Diagnostic markers can help identify patients at risk for sepsis and AKI, allowing for early intervention and potentially preventing the development of severe complications. The aim of the present study was to investigate the expression difference of urinary microRNAs (miRNAs/miRs) in elderly patients with sepsis and secondary renal insufficiency, and to evaluate their diagnostic value in these patients. In the present study, RNA was extracted from urine samples of elderly sepsis-related acute renal damage patients and the expression profiles of several miRNAs were analyzed. In order to evaluate the expression profile of several miRNAs, urine samples from elderly patients with acute renal damage brought on by sepsis were obtained. RNA extraction and sequencing were then performed on the samples. Furthermore, multiple bioinformatics methods were used to analyze miRNA profiles, including differential expression analysis, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of different miRNA target genes, to further explore miRNAs that are suitable for utilization as biomarkers. A total of four miRNAs, including hsa-miR-31-5p, hsa-miR-151a-3p, hsa-miR-142-5p and hsa-miR-16-5p, were identified as potential biological markers and were further confirmed in sepsis using reverse transcription-quantitative PCR. The results of the present study demonstrated that the four urinary miRNAs were differentially expressed and may serve as specific markers for prediction of secondary acute kidney injury in elderly patients with sepsis.
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Lung cancer is a highly heterogeneous disease. Cancer cells and other cells within the tumor microenvironment interact to determine disease progression, as well as response to or escape from treatment. Understanding the regulatory relationship between cancer cells and their tumor microenvironment in lung adenocarcinoma is of great significance for exploring the heterogeneity of the tumor microenvironment and its role in the genesis and development of lung adenocarcinoma. This work uses public single-cell transcriptome data (distant normal, nLung; early LUAD, tLung; advanced LUAD, tL/B), to draft a cell map of lung adenocarcinoma from onset to progression, and provide a cell-cell communication view of lung adenocarcinoma in the different disease stages. Based on the analysis of cell populations, it was found that the proportion of macrophages was significantly reduced in the development of lung adenocarcinoma, and patients with lower proportions of macrophages exhibited poor prognosis. We therefore constructed a process to screen an intercellular gene regulatory network that reduces any error generated by single cell communication analysis and increases the credibility of selected cell communication signals. Based on the key regulatory signals in the macrophage-tumor cell regulatory network, we performed a pseudotime analysis of the macrophages and found that signal molecules (TIMP1, VEGFA, SPP1) are highly expressed in immunosuppression-associated macrophages. These molecules were also validated using an independent dataset and were significantly associated with poor prognosis. Our study provides an effective method for screening the key regulatory signals in the tumor microenvironment and the selected signal molecules may serve as a reference to guide the development of diagnostic biomarkers for risk stratification and therapeutic targets for lung adenocarcinoma.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Humans , Gene Regulatory Networks , Adenocarcinoma of Lung/genetics , Genes, Regulator , Lung Neoplasms/genetics , Tumor Microenvironment/genetics , Sequence Analysis, RNA , Biomarkers, Tumor , Gene Expression Regulation, NeoplasticABSTRACT
Neoantigens recognized by cytotoxic T cells are effective targets for tumor-specific immune responses for personalized cancer immunotherapy. Quite a few neoantigen identification pipelines and computational strategies have been developed to improve the accuracy of the peptide selection process. However, these methods mainly consider the neoantigen end and ignore the interaction between peptide-TCR and the preference of each residue in TCRs, resulting in the filtered peptides often fail to truly elicit an immune response. Here, we propose a novel encoding approach for peptide-TCR representation. Subsequently, a deep learning framework, namely iTCep, was developed to predict the interactions between peptides and TCRs using fusion features derived from a feature-level fusion strategy. The iTCep achieved high predictive performance with AUC up to 0.96 on the testing dataset and above 0.86 on independent datasets, presenting better prediction performance compared with other predictors. Our results provided strong evidence that model iTCep can be a reliable and robust method for predicting TCR binding specificities of given antigen peptides. One can access the iTCep through a user-friendly web server at http://biostatistics.online/iTCep/, which supports prediction modes of peptide-TCR pairs and peptide-only. A stand-alone software program for T cell epitope prediction is also available for convenient installing at https://github.com/kbvstmd/iTCep/.
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The complex nature of liquid water saturation of polymer electrolyte fuel cell (PEFC) catalyst layers (CLs) greatly affects the device performance. To investigate this problem, we present a method to quantify the presence of liquid water in a PEFC CL using small-angle X-ray scattering (SAXS). This method leverages the differences in electron densities between the solid catalyst matrix and the liquid water filled pores of the CL under both dry and wet conditions. This approach is validated using ex situ wetting experiments, which aid the study of the transient saturation of a CL in a flow cell configuration in situ. The azimuthally integrated scattering data are fitted using 3D morphology models of the CL under dry conditions. Different wetting scenarios are realized in silico, and the corresponding SAXS data are numerically simulated by a direct 3D Fourier transformation. The simulated SAXS profiles of the different wetting scenarios are used to interpret the measured SAXS data which allows the derivation of the most probable wetting mechanism within a flow cell electrode.
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Delivery of double emulsions in air is crucial for their applications in mass spectrometry, bioanalytics, and material synthesis. However, while methods have been developed to generate double emulsions in air, controlled printing of double emulsion droplets has not been achieved yet. In this paper, we present an approach for in-air printing of double emulsions on demand. Our approach pre-encapsulates reagents in an emulsion that is reinjected into the device, and generates double emulsions in a microfluidic printhead with spatially patterned wettability. Our device allows sorting of ejected double emulsion droplets in real-time, allowing deterministic printing of each droplet to be selected with the desired inner cores. Our method provides a general platform for building printed double emulsion droplet arrays of defined composition at scale.