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1.
Sensors (Basel) ; 24(17)2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39275670

ABSTRACT

The deep integration of communication and sensing technology in fiber-optic systems has been highly sought after in recent years, with the aim of rapid and cost-effective large-scale upgrading of existing communication cables in order to monitor ocean activities. As a proof-of-concept demonstration, a high-degree of compatibility was shown between forward-transmission distributed fiber-optic vibration sensing and an on-off keying (OOK)-based communication system. This type of deep integration allows distributed sensing to utilize the optical fiber communication cable, wavelength channel, optical signal and demodulation receiver. The addition of distributed sensing functionality does not have an impact on the communication performance, as sensing involves no hardware changes and does not occupy any bandwidth; instead, it non-intrusively analyzes inherent vibration-induced noise in the data transmitted. Likewise, the transmission of communication data does not affect the sensing performance. For data transmission, 150 Mb/s was demonstrated with a BER of 2.8 × 10-7 and a QdB of 14.1. For vibration sensing, the forward-transmission method offers distance, time, frequency, intensity and phase-resolved monitoring. The limit of detection (LoD) is 8.3 pε/Hz1/2 at 1 kHz. The single-span sensing distance is 101.3 km (no optical amplification), with a spatial resolution of 0.08 m, and positioning accuracy can be as low as 10.1 m. No data averaging was performed during signal processing. The vibration frequency range tested is 10-1000 Hz.

2.
Opt Lett ; 49(16): 4759-4762, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39146154

ABSTRACT

Multi-dimensional orbital angular momentum (OAM) mode multiplexing provides a promising route for enlarging communication capacity and establishing comprehensive networks. While multi-dimensional multiplexing has gained advancements, the cross-connection of these multiplexed channels, especially involving modes and polarizations, remains challenging due to the needs for multi-mode interconversion and on-demand polarization control. Herein, we propose an OAM mode-polarization cross-transformation solution via cascaded partitioned phase modulation, which enables the divergently separated OAM modes to be independently phase-imposed within distinct spatial regions, leading to the synergistic conversion operation of mode and polarization channels. In demonstrations, we implemented the cross-connection of three OAM modes and two polarization multiplexed channels, achieving the mode purity that exceeds 0.951 and polarization contrast up to 0.947. The measured mode insertion losses and polarization conversion losses are below 3.42 and 3.54 dB, respectively. Consequently, 1.2 Tbit/s quadrature phase shift keying signals were successfully exchanged, yielding the bit-error-rates close to 10-6. Incorporating with increased partitioned phase treatments, this approach shows promise in accommodating massive mode-polarization multiplexed channels, which hold the potential to augment networking capability of large-scale OAM mode multiplexing communication networks.

3.
Sensors (Basel) ; 24(16)2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39204952

ABSTRACT

For distributed fiber-optic sensors, slowly varying vibration signals down to 5 mHz are difficult to measure due to low signal-to-noise ratios. We propose and demonstrate a forward transmission-based distributed sensing system, combined with a polarization-generated carrier for detection bandwidth reduction, and cross-correlation for vibration positioning. By applying a higher-frequency carrier signal using a fast polarization controller, the initial phase of the known carrier frequency is monitored and analyzed to demodulate the vibration signal. Only the polarization carrier needs to be analyzed, not the arbitrary-frequency signal, which can lead to hardware issues (reduced detection bandwidth and less noise). The difference in arrival time between the two detection ends obtained through cross-correlation can determine the vibration position. Our experimental results demonstrate a sensitivity of 0.63 mrad/µÎµ and a limit of detection (LoD) of 355.6 pε/Hz1/2 at 60 Hz. A lock-in amplifier can be used on the fixed carrier to achieve a minimal LoD. The sensing distance can reach 131.5 km and the positioning accuracy is 725 m (root-mean-square error) while the spatial resolution is 105 m. The tested vibration frequency range is between 0.005 Hz and 160 Hz. A low frequency of 5 mHz for forward transmission-based distributed sensing is highly attractive for seismic monitoring applications.

4.
Mol Ther Oncol ; 32(3): 200827, 2024 Sep 19.
Article in English | MEDLINE | ID: mdl-39027379

ABSTRACT

Inadequate antigen-specific T cells activation hampers immunotherapy due to complex antigen presentation. In addition, therapeutic in vivo T cell expansion is constrained by slow expansion rates and limited functionality. Herein, we introduce a model fusion protein termed antigen-presenting cell-mimic fusion protein (APC-mimic), designed to greatly mimicking the natural antigen presentation pattern of antigen-presenting cells and directly expand T cells both in vitro and in vivo. The APC-mimic comprises the cognate peptide-human leukocyte antigen (pHLA) complex and the co-stimulatory marker CD80, which are natural ligands on APCs. Following a single stimulation, APC-mimic leads to an approximately 400-fold increase in the polyclonal expansion of antigen-specific T cells compared with the untreated group in vitro without the requirement for specialized antigen-presenting cells. Through the combination of single-cell TCR sequencing (scTCR-seq) and single-cell RNA sequencing (scRNA-seq), we identify an approximately 600-fold monoclonal expansion clonotype among these polyclonal clonotypes. It also exhibits suitability for in vivo applications confirmed in the OT-1 mouse model. Furthermore, T cells expanded by APC-mimic effectively inhibits tumor growth in adoptive cell transfer (ACT) murine models. These findings pave the way for the versatile APC-mimic platform for personalized therapeutics, enabling direct expansion of polyfunctional antigen-specific T cell subsets in vitro and in vivo.

5.
Methods Mol Biol ; 2809: 237-244, 2024.
Article in English | MEDLINE | ID: mdl-38907901

ABSTRACT

Neoantigens are crucial in distinguishing cancer cells from normal ones and play a significant role in cancer immunotherapy. The field of bioinformatics prediction for tumor neoantigens has rapidly developed, focusing on the prediction of peptide-HLA binding affinity. In this chapter, we introduce a user-friendly tool named DeepHLApan, which utilizes deep learning techniques to predict neoantigens by considering both peptide-HLA binding affinity and immunogenicity. We provide the application of DeepHLApan, along with the source code, docker version, and web-server. These resources are freely available at https://github.com/zjupgx/deephlapan and http://pgx.zju.edu.cn/deephlapan/ .


Subject(s)
Computational Biology , Deep Learning , HLA Antigens , Peptides , Software , Humans , Peptides/immunology , Peptides/chemistry , Computational Biology/methods , HLA Antigens/immunology , Antigens, Neoplasm/immunology , Antigens, Neoplasm/metabolism , Protein Binding , Neoplasms/immunology
6.
Opt Lett ; 49(10): 2533-2536, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38748098

ABSTRACT

Cylindrical vector beam (CVB) multiplexing communication demands effective mode cross-connection techniques to establish communication networks. While methods like polarized grating and coordinate transformation have been developed for (de)multiplexing CVB modes, challenges persist in the cross-connection of these multiplexed mode channels, including multi-mode conversion and inhomogeneous polarization control. Herein, we present an independent off-axis spin-orbit interaction strategy utilizing spin-decoupled metasurfaces. Cross-connection is achieved by encoding conjugated Dammann optical vortex grating phases onto the two orthogonal circularly polarized components of CVBs. Experimental results demonstrate the successful interconversion of four CVB modes (CVB+1 and CVB-2, CVB+2 and CVB-4) using a Si-based metasurface with a polarization conversion efficiency exceeding 85%. This facilitates the cross-connection of 200 Gbit/s quadrature phase-shift keying signals with bit-error-rates below 10-6. Offering advantages such as ultra-compact device size, flexible control of CVB modes, and multi-mode parallel processing, this approach shows promise in advancing the networking capabilities of CVB mode multiplexing communication networks.

7.
Brief Bioinform ; 25(3)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38653491

ABSTRACT

Coronaviruses have threatened humans repeatedly, especially COVID-19 caused by SARS-CoV-2, which has posed a substantial threat to global public health. SARS-CoV-2 continuously evolves through random mutation, resulting in a significant decrease in the efficacy of existing vaccines and neutralizing antibody drugs. It is critical to assess immune escape caused by viral mutations and develop broad-spectrum vaccines and neutralizing antibodies targeting conserved epitopes. Thus, we constructed CovEpiAb, a comprehensive database and analysis resource of human coronavirus (HCoVs) immune epitopes and antibodies. CovEpiAb contains information on over 60 000 experimentally validated epitopes and over 12 000 antibodies for HCoVs and SARS-CoV-2 variants. The database is unique in (1) classifying and annotating cross-reactive epitopes from different viruses and variants; (2) providing molecular and experimental interaction profiles of antibodies, including structure-based binding sites and around 70 000 data on binding affinity and neutralizing activity; (3) providing virological characteristics of current and past circulating SARS-CoV-2 variants and in vitro activity of various therapeutics; and (4) offering site-level annotations of key functional features, including antibody binding, immunological epitopes, SARS-CoV-2 mutations and conservation across HCoVs. In addition, we developed an integrated pipeline for epitope prediction named COVEP, which is available from the webpage of CovEpiAb. CovEpiAb is freely accessible at https://pgx.zju.edu.cn/covepiab/.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , Epitopes , SARS-CoV-2 , Humans , SARS-CoV-2/immunology , SARS-CoV-2/genetics , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/virology , Antibodies, Neutralizing/immunology , Epitopes/immunology , Epitopes/chemistry , Epitopes/genetics , Coronavirus/immunology , Coronavirus/genetics , Databases, Factual , Cross Reactions/immunology
8.
Biomedicines ; 12(4)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38672132

ABSTRACT

Antibody-based bispecific T cell engagers (TCEs) that redirect T cells to kill tumor cells have shown a promising therapeutic effect on hematologic malignancies. However, tumor-specific targeting is still a challenge for TCEs, impeding the development of TCEs for solid tumor therapy. The major histocompatibility complex (MHC) presents almost all intracellular peptides (including tumor-specific peptides) on the cell surface to be scanned by the TCR on T cells. With the premise of choosing optimal peptides, the final complex peptide-MHC could be the tumor-specific target for TCEs. Here, a novel TCR-directed format of a TCE targeting peptide-MHC was designed named IgG-T-TCE, which was modified from the IgG backbone and prepared in a mammalian cell expression system. The recombinant IgG-T-TCE-NY targeting NY-ESO-1157-165/HLA-A*02:01 could be generated in HEK293 cells with a glycosylated TCR and showed potency in T cell activation and redirecting T cells to specifically kill target tumor cells. We also found that the in vitro activity of IgG-T-TCE-NY could be leveraged by various anti-CD3 antibodies and Fc silencing. The IgG-T-TCE-NY efficiently inhibited tumor growth in a tumor-PBMC co-engrafted mouse model without any obvious toxicities.

9.
Opt Express ; 32(6): 9634-9643, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38571193

ABSTRACT

Cylindrical vector beams (CVBs) exhibit great potential for multiplexing communication, owing to their mode orthogonality and compatibility with conventional wavelength multiplexing techniques. However, the practical application of CVB multiplexing communication faces challenges due to the lack of effective spatial polarization manipulation technologies for (de)multiplexing multi-dimensional physical dimensions of CVBs. Herein, we introduce a wavelength- and polarization-sensitive cascaded phase modulation strategy that utilizes multiple coaxial metasurfaces for multi-dimensional modulation of CVBs. By leveraging the spin-dependent phase modulation mechanism, these metasurfaces enable the independent transformation of the two orthogonal polarization components of CVB modes. Combined with the wavelength sensitivity of Fresnel diffraction in progressive phase modulation, this approach establishes a high-dimensional mapping relationship among CVB modes, wavelengths, spatial positions, and Gaussian fundamental modes, thereby facilitating multi-dimensional (de)multiplexing involving CVB modes and wavelengths. As a proof of concept, we theoretically demonstrate a 9-channel multi-dimensional multiplexing system, successfully achieving joint (de)multiplexing of 3 CVB modes (1, 2, and 3) and 3 wavelengths (1550 nm, 1560 nm, and 1570 nm) with a diffraction efficiency exceeding 80%. Additionally, we show the transmission of 16-QAM signals across 9 channels with the bit-error-rates below 10-5. By combining the integrability of metasurfaces with the high-dimensional wavefront manipulation capabilities of multilevel modulation, our strategy can effectively address the diverse demands of different wavelengths and CVB modes in optical communication.

10.
Methods Mol Biol ; 2793: 41-54, 2024.
Article in English | MEDLINE | ID: mdl-38526722

ABSTRACT

Resistance to therapeutic antibodies caused by on-target point mutations is a major obstacle in anticancer therapy, creating an "unmet clinical need." To tackle this problem, researchers are developing new generations of antibody drugs that can overcome the resistance mechanisms of existing agents. We have previously reported a structure-guided and phage-assisted evolution (SGAPAE) approach to evolve cetuximab, a therapeutic antibody, to effectively reverse the resistance driven by EGFRS492R or EGFRG465R mutations, without changing the binding epitope or compromising the antibody efficacy. In this protocol, we provide detailed instructions on how to use the SGAPAE approach to evolve cetuximab, which can also be applied to other therapeutic antibodies for reversing on-target point mutation-mediated resistance. The protocol consists of four steps: structure preparation, computational prediction, phage display library construction, and antibody candidate selection.


Subject(s)
Antibodies, Monoclonal , Bacteriophages , Cetuximab , Point Mutation , ErbB Receptors/metabolism , Bacteriophages/metabolism , Antibodies, Monoclonal, Humanized/genetics
11.
Sci Immunol ; 9(92): eadj3945, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38363830

ABSTRACT

Stimulator of interferon genes (STING) is an immune adaptor protein that senses cyclic GMP-AMP in response to self or microbial cytosolic DNA as a danger signal. STING is ubiquitously expressed in diverse cell populations, including cancer cells, with distinct cellular functions, such as activation of type I interferons, autophagy induction, or triggering apoptosis. It is not well understood whether and which subsets of immune cells, stromal cells, or cancer cells are particularly important for STING-mediated antitumor immunity. Here, using a polymeric STING-activating nanoparticle (PolySTING) with a shock-and-lock dual activation mechanism, we show that conventional type 1 dendritic cells (cDC1s) are essential for STING-mediated rejection of multiple established and metastatic murine tumors. STING status in the host but not in the cancer cells (Tmem173-/-) is important for antitumor efficacy. Specific depletion of cDC1 (Batf3-/-) or STING deficiency in cDC1 (XCR1creSTINGfl/fl) abolished PolySTING efficacy, whereas depletion of other myeloid cells had little effect. Adoptive transfer of wild-type cDC1 in Batf3-/- mice restored antitumor efficacy, whereas transfer of cDC1 with STING or IRF3 deficiency failed to rescue. PolySTING induced a specific chemokine signature in wild-type but not Batf3-/- mice. Multiplexed immunohistochemistry analysis of STING-activating cDC1s in resected tumors correlates with patient survival. Furthermore, STING-cDC1 signature was increased after neoadjuvant pembrolizumab therapy in patients with non-small cell lung cancer. Therefore, we have defined that a subset of myeloid cells is essential for STING-mediated antitumor immunity with associated biomarkers for prognosis.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Interferon Type I , Lung Neoplasms , Animals , Humans , Mice , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/therapy , Dendritic Cells , DNA/metabolism , Interferon Type I/metabolism , Nanoparticles/therapeutic use , Immunotherapy/methods
12.
bioRxiv ; 2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38260493

ABSTRACT

Stimulator of interferon genes (STING) is an immune adaptor protein that senses cyclic GMP-AMP (cGAMP) in response to self or microbial cytosolic DNA as a danger signal. STING is ubiquitously expressed in diverse cell populations including cancer cells with distinct cellular functions such as activation of type I interferons, autophagy induction, or triggering apoptosis. It is not well understood whether and which subsets of immune cells, stromal cells, or cancer cells are particularly important for STING-mediated antitumor immunity. Here using a polymeric STING-activating nanoparticle (PolySTING) with a "shock-and-lock" dual activation mechanism, we show type 1 conventional dendritic cell (cDC1) is essential for STING-mediated rejection of multiple established and metastatic murine tumors. STING status in the host but not in the cancer cells ( Tmem173 -/- ) is important for antitumor efficacy. Specific depletion of cDC1 ( Batf3 -/- ) or STING deficiency in cDC1 ( XCR1 cre STING fl/fl ) abolished PolySTING efficacy, whereas depletion of other myeloid cells had little effect. Adoptive transfer of wildtype cDC1 in Batf3 -/- mice restored antitumor efficacy while transfer of cDC1 with STING or IRF3 deficiency failed to rescue. PolySTING induced a specific chemokine signature in wildtype but not Batf3 -/- mice. Multiplexed immunohistochemistry analysis of STING-activating cDC1s in resected tumors correlates with patient survival while also showing increased expressions after neoadjuvant pembrolizumab therapy in non-small cell lung cancer patients. Therefore, we have defined that a subset of myeloid cells is essential for STING-mediated antitumor immunity with associated biomarkers for prognosis. One Sentence Summary: A "shock-and-lock" nanoparticle agonist induces direct STING signaling in type 1 conventional dendritic cells to drive antitumor immunity with defined biomarkers.

13.
Int Wound J ; 21(1): e14384, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37697692

ABSTRACT

Pathological scarring resulting from traumas and wounds, such as hypertrophic scars and keloids, pose significant aesthetic, functional and psychological challenges. This study provides a comprehensive transcriptomic analysis of these conditions, aiming to illuminate underlying molecular mechanisms and potential therapeutic targets. We employed a co-expression and module analysis tool to identify significant gene clusters associated with distinct pathophysiological processes and mechanisms, notably lipid metabolism, sebum production, cellular energy metabolism and skin barrier function. This examination yielded critical insights into several skin conditions including folliculitis, skin fibrosis, fibrosarcoma and congenital ichthyosis. Particular attention was paid to Module Cluster (MCluster) 3, encompassing genes like BLK, TRPV1 and GABRD, all displaying high expression and potential implications in immune modulation. Preliminary immunohistochemistry validation supported these findings, showing elevated expression of these genes in non-fibrotic samples rich in immune activity. The complex interplay of different cell types in scar formation, such as fibroblasts, myofibroblasts, keratinocytes and mast cells, was also explored, revealing promising therapeutic strategies. This study underscores the promise of targeted gene therapy for pathological scars, paving the way for more personalised therapeutic approaches. The results necessitate further research to fully ascertain the roles of these identified genes and pathways in skin disease pathogenesis and potential therapeutics. Nonetheless, our work forms a strong foundation for a new era of personalised medicine for patients suffering from pathological scarring.


Subject(s)
Cicatrix, Hypertrophic , Keloid , Humans , Cicatrix, Hypertrophic/genetics , Cicatrix, Hypertrophic/therapy , Cicatrix, Hypertrophic/metabolism , Keloid/genetics , Keloid/therapy , Keratinocytes/metabolism , Fibroblasts/metabolism , Myofibroblasts/metabolism
14.
Mol Ther ; 32(2): 490-502, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38098228

ABSTRACT

Inadequate T cell activation has severely limited the success of T cell engager (TCE) therapy, especially in solid tumors. Enhancing T cell activity while maintaining the tumor specificity of TCEs is the key to improving their clinical efficacy. However, currently, there needs to be more effective strategies in clinical practice. Here, we design novel superantigen-fused TCEs that display robust tumor antigen-mediated T cell activation effects. These innovative drugs are not only armed with the powerful T cell activation ability of superantigens but also retain the dependence of TCEs on tumor antigens, realizing the ingenious combination of the advantages of two existing drugs. Superantigen-fused TCEs have been preliminarily proven to have good (>30-fold more potent) and specific (>25-fold more potent) antitumor activity in vitro and in vivo. Surprisingly, they can also induce the activation of T cell chemotaxis signals, which may promote T cell infiltration and further provide an additional guarantee for improving TCE efficacy in solid tumors. Overall, this proof-of-concept provides a potential strategy for improving the clinical efficacy of TCEs.


Subject(s)
Neoplasms , T-Lymphocytes , Humans , Superantigens/therapeutic use , Antigens, Neoplasm , Cell Death
15.
Opt Express ; 31(25): 42299-42309, 2023 Dec 04.
Article in English | MEDLINE | ID: mdl-38087606

ABSTRACT

Cylindrical vector beam (CVB) has recently gained attention as a promising carrier for signal multiplexing owing to its mode orthogonality. However, the full-duplex multiplexing communication has not been previously explored for the lack of effective technologies to parallelly couple and separate CVB modes. Herein, we present a full-duplex solution for CVB multiplexing communication that utilizes spin-dependent phase modulation metasurfaces. By independently phase-modulating the two spin eigenstates of CVBs with the metasurface via spin-dependent orbital interactions, and loading two binary Dammann vortex gratings, we enabled an independent and reciprocal wave vector manipulation of CVBs for full-duplex (de)multiplexing operation. To demonstrate this concept, we constructed a 16-channel (including 4 CVB modes and 4 wavelengths) full-duplex CVB multiplexing communication system and achieved the bidirectional transmission of 800 Gbit/s quadrature-phase shift-keying (QPSK) signals over a 5 km few-mode fiber. Our results demonstrate the successful multiplexing and demultiplexing of 2 radial CVB modes and 2 azimuthal CVB modes in full-duplex communication with the bit-error-rates approaching 1.87 × 10-5.

16.
Cancers (Basel) ; 15(24)2023 Dec 09.
Article in English | MEDLINE | ID: mdl-38136320

ABSTRACT

At present, multiple myeloma (MM) is still an essentially incurable hematologic malignancy. Although BCMA-targeted therapies have achieved remarkable results, BCMA levels were found to be downregulated in patients with MM who relapsed after these treatments. Therefore, the search for other antigens specific to MM has become a priority. Independently of BCMA expression, G-protein-coupled receptor family C group 5 member D (GPRC5D) is mainly expressed in the plasma cells of MM patients, while it is expressed in a limited number of normal tissues. Combining MM-specific antigen GPRC5D and T-cell-mediated therapies would be a promising therapeutic strategy for MM. Recently, we constructed a new anti-GPRC5D × anti-CD3 T-cell-engaging bispecific antibody (TCB), BR109, which was capable of binding to human GPRC5D and human CD3ε. Moreover, BR109 was proven to have relatively good stability and antitumor activity. BR109 could specifically trigger T-cell-mediated cytotoxicity against many GPRC5D-positive MM cells in vitro. Meanwhile, antitumor activity was demonstrated in MM cell line xenograft mouse models with human immune cell reconstitution. These preclinical studies have formed a solid foundation for the evaluation of MM treatment efficacy in clinical trials.

17.
Front Microbiol ; 14: 1230738, 2023.
Article in English | MEDLINE | ID: mdl-38029111

ABSTRACT

Here, an α-L-arabinofuranosidase (termed TtAbf62) from Thermothelomyces thermophilus is described, which efficiently removes arabinofuranosyl side chains and facilitates arabinoxylan digestion. The specific activity of TtAbf62 (179.07 U/mg) toward wheat arabinoxylan was the highest among all characterized glycoside hydrolase family 62 enzymes. TtAbf62 in combination with endoxylanase and ß-xylosidase strongly promoted hydrolysis of barley and wheat. The release of reducing sugars was significantly higher for the three-enzyme combination relative to the sum of single-enzyme treatments: 85.71% for barley hydrolysis and 33.33% for wheat hydrolysis. HPLC analysis showed that TtAbf62 acted selectively on monosubstituted (C-2 or C-3) xylopyranosyl residues rather than double-substituted residues. Site-directed mutagenesis and interactional analyses of enzyme-substrate binding structures revealed the catalytic sites of TtAbf62 formed different polysaccharide-catalytic binding modes with arabinoxylo-oligosaccharides. Our findings demonstrate a "multienzyme cocktail" formed by TtAbf62 with other hydrolases strongly improves the efficiency of hemicellulose conversion and increases biomass hydrolysis through synergistic interaction.

18.
Comput Biol Med ; 164: 107247, 2023 09.
Article in English | MEDLINE | ID: mdl-37454505

ABSTRACT

The transport of peptides from the cytoplasm to the endoplasmic reticulum (ER) by transporters associated with antigen processing (TAP) is a critical step in the intracellular presentation of cytotoxic T lymphocyte (CTL) epitopes. The development and application of computational methods, especially deep learning methods and new neural network strategies that can automatically learn feature representations with limited knowledge, provide an opportunity to develop fast and efficient methods to identify TAP-binding peptides. Herein, this study presents a comprehensive analysis of TAP-binding peptide sequences to derive TAP-binding motifs and preferences for N-terminal and C-terminal amino acids. A novel recurrent neural network (RNN)-based method called DeepTAP, using bidirectional gated recurrent unit (BiGRU), was developed for the accurate prediction of TAP-binding peptides. Our results demonstrated that DeepTAP achieves an optimal balance between prediction precision and false positives, outperforming other baseline models. Furthermore, DeepTAP significantly improves the prediction accuracy of high-confidence neoantigens, especially the top-ranked ones, making it a valuable tool for researchers studying antigen presentation processes and T-cell epitope screening. DeepTAP is freely available at https://github.com/zjupgx/deeptap and https://pgx.zju.edu.cn/deeptap.


Subject(s)
Antigen Presentation , Neoplasms , Humans , ATP-Binding Cassette Transporters/metabolism , Peptides/metabolism , Epitopes, T-Lymphocyte , Neural Networks, Computer
19.
Front Cardiovasc Med ; 10: 1110742, 2023.
Article in English | MEDLINE | ID: mdl-37139133

ABSTRACT

Background: Little is known about the role of interleukin (IL) in patients with acute myocardial infarction (MI), especially soluble IL-2 receptor (sIL-2R) and IL-8. We aim to evaluate, in MI patients, the predictive value of serum sIL-2R and IL-8 for future major adverse cardiovascular events (MACEs), and compare them with current biomarkers reflecting myocardial inflammation and injury. Methods: This was a prospective, single-center cohort study. We measured serum concentrations of IL-1ß, sIL-2R, IL-6, IL-8 and IL-10. Levels of current biomarkers for predicting MACEs were measured, including high-sensitivity C reactive protein, cardiac troponin T and N-terminal pro-brain natriuretic peptide. Clinical events were collected during 1-year and a median of 2.2 years (long-term) follow-up. Results: Twenty-four patients (13.8%, 24/173) experienced MACEs during 1-year follow-up and 40 patients (23.1%, 40/173) during long-term follow-up. Of the five interleukins studied, only sIL-2R and IL-8 were independently associated with endpoints during 1-year or long-term follow-up. Patients with high sIL-2R or IL-8 levels (higher than the cutoff value) had a significantly higher risk of MACEs during 1-year (sIL-2R: HR 7.7, 3.3-18.0, p < 0.001; IL-8: HR 4.8, 2.1-10.7, p < 0.001) and long-term (sIL-2R: HR 7.7, 3.3-18.0, p < 0.001; IL-8: HR 4.8, 2.1-10.7, p < 0.001) follow-up. Receiver operator characteristic curve analysis regarding predictive accuracy for MACEs during 1-year follow-up showed that the area under the curve for sIL-2R, IL-8, sIL-2R combined with IL-8 was 0.66 (0.54-0.79, p = 0.011), 0.69 (0.56-0.82, p < 0.001) and 0.720 (0.59-0.85, p < 0.001), whose predictive value were superior to that of current biomarkers. The addition of sIL-2R combined with IL-8 to the existing prediction model resulted in a significant improvement in predictive power (p = 0.029), prompting a 20.8% increase in the proportion of correct classifications. Conclusions: High serum sIL-2R combined with IL-8 levels was significantly associated with MACEs during follow-up in patients with MI, suggesting that sIL-2R combined with IL-8 may be a helpful biomarker for identifying the increased risk of new cardiovascular events. IL-2 and IL-8 would be promising therapeutic targets for anti-inflammatory therapy.

20.
Nanomaterials (Basel) ; 13(8)2023 Apr 20.
Article in English | MEDLINE | ID: mdl-37111008

ABSTRACT

Vortex beams with optical orbital angular momentum have broad prospects in future high-speed and large-capacity optical communication. In this investigation of materials science, we found that low-dimensional materials have feasibility and reliability in the development of optical logic gates in all-optical signal processing and computing technology. We found that spatial self-phase modulation patterns through the MoS2 dispersions can be modulated by the initial intensity, phase, and topological charge of a Gauss vortex superposition interference beam. We utilized these three degrees of freedom as the input signals of the optical logic gate, and the intensity of a selected checkpoint on spatial self-phase modulation patterns as the output signal. By setting appropriate thresholds as logic codes 0 and 1, two sets of novel optical logic gates, including AND, OR, and NOT gates, were implemented. These optical logic gates are expected to have great potential in optical logic operations, all-optical networks, and all-optical signal processing.

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