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The effect of surface modification on enhancing the magnetic heating behavior of magnetic nano fluids were investigated, for this purpose Fe3O4 nanoparticles were synthesized using co-precipitation method and surface modification was done using citric acid, ascorbic acid, tetraethyl orthosilicate (TEOS), polyvinyl alcohol (PVA) and polyethylene glycol (PEG). Experimental heating tests using AC magnetic field were done in the frequency of 100 kHz and different magnetic field (H) intensities. Theoretically the specific absorption rate (SAR) in magnetic nano fluids is independent of nanoparticles concentration but the experimental results showed different behavior. The theoretical SAR value @ H = 12kA.m–1 for Nano fluids containing bare Fe3O4 nanoparticles was 11.5 W/g but in experimental tests the obtained value was 9.72 W/g for nano fluid containing 20,000 ppm of dispersed nanoparticles. The experimental SAR calculation was repeated for sample containing 10,000 ppm of nanoparticles and the results showed increase in experimental SAR that is an evidence of nanoparticles agglomeration in higher concentrations. The surface modification has improved the dispersion ability of the nanoparticles. The Ratio of SAR, experimental, 20000ppm to SAR, experimental, 10000ppm was 0.85 for bare Fe3O4 nanoparticles dispersion but in case of surface modified nanoparticles this ratio has increased up to 0.98 that shows lower agglomeration of nanoparticles as a result of surface modification, although on the other hand the surface modification agents were magnetically passive and so it is expected that in constant concentration the SAR for bare Fe3O4 nanoparticles to be higher than this variable for surface modified nanoparticles. At lower concentrations the dispersions containing bare Fe3O4 nanoparticles showed higher SAR values but at higher concentrations the surface modified Fe3O4 nanoparticles showed better results although the active agent amount was lower at them. Finally, it should be noted that the nanoparticles that were surface modified using polymeric agents showed the highest decrease in experimental SAR amounts comparing theoretical results that was because of the large molecules of polymers comparing other implemented surface modification agents. [ABSTRACT FROM AUTHOR]

Background: Electromagnetic induction hyperthermia is a promising method to treat the deep-seated tumors such as brain and prostatic tumors. This technique is performed using the induction of electromagnetic waves in the ferromagnetic cores implanted at the solid tumor. Objective: This study aims at determining the conditions of the optimal thermal distribution in the different frequencies before performing the in vitro cellular study. Material and Methods: In this experimental study, the i-Cu alloy (70.4-29.6; wt%) was prepared and characterized and then the parameters, affecting the amount of induction heating in the ferromagnetic core, were investigated. Self-regulating cores in 1, 3, 6, and 9 arrangements in the water phantom with a volume of 2 cm3 were used as a replacement for solid tumor. Results: Inductively Coupled Plasma (ICP) analysis and Energy Dispersive X-ray Spectroscopy (EDS) show the uniformity of the alloy after 4 times remeling by vacuum arc remelting furnace. The Vibrating Sample Magnetometer (VSM) shows that the Curie temperature (TC) of the ferromagnetic core is less than 50 °C. Temperature profile with a frequency of 100-400 kHz for 30 min, was extracted by infrared imaging camera, indicating the increase temperature in the range of 42 °C to 46 °C. Conclusion: The optimum conditions with used hyperthermia system are supplied in the frequency of 100 kHz, 200 kHz and 400 kHz with 6, 3 and 1 seeds, respectively. It is also possible to induce a temperature up to 50 °C by increasing the number of seeds at a constant frequency and power, or by increasing the applied frequency at a constant number of seeds. [ABSTRACT FROM AUTHOR]

As one of the most well-known metal nanoparticles, gold nanoparticles (AuNPs) have attracted much attention for the biological applications. This great interest in AuNPs can be attributed to their outstanding physical and chemical properties, such as special optical and electrochemical characteristics, high X-ray attenuation ability, strong X-ray absorption, photothermal effect, stability and biocompatibility. In addition, due to the ease of synthesis and modification of the surface of AuNPs, it is possible to control their shape, size and surface characteristics. All these features suggest that AuNPs can be used for biosensing strategies, drug delivery, photothermal therapy, nanobrachytherapy, enhanced radiotherapy and CT imaging. In addition, they can be used as antibacterial and antifungal agents. This minireview focuses on the key principles, research achievements and new opportunities in the synthesis of AuNPs as well as their biological applications. In fact, the growing progress in the use of AuNPs for the diagnostic and therapeutic applications is described in this survey. Overall, a better understanding of the key aspects of the synthesis methodologies will lead to the development of new protocols that can provide ideas for more cost-effective and reliable approaches to the production of AuNPs. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that the presence and spatial localization and distribution pattern of tumor infiltrating lymphocytes (TILs) is associate with response to immunotherapies. Recent studies have identified TGF β activity and signaling as a determinant of T cell exclusion in the tumor microenvironment and poor response to PD-1/PD-L1 blockade. Here we coupled the artificial intelligence (AI)-powered digital image analysis and gene expression profiling as an integrative approach to quantify distribution of TILs and characterize the associated TGF β pathway activity. Analysis of T cell spatial distribution in the solid tumor biopsies revealed substantial differences in the distribution patterns. The digital image analysis approach achieves 74% concordance with the pathologist assessment for tumor-immune phenotypes. The transcriptomic profiling suggests that the TIL score was negatively correlated with TGF β pathway activation, together with elevated TGF β signaling activity observed in excluded and desert tumor phenotypes. The present results demonstrate that the automated digital pathology algorithm for quantitative analysis of CD8 immunohistochemistry image can successfully assign the tumor into one of three infiltration phenotypes: immune desert, immune excluded or immune inflamed. The association between "cold" tumor-immune phenotypes and TGF β signature further demonstrates their potential as predictive biomarkers to identify appropriate patients that may benefit from TGF β blockade. An artificial intelligence-powered digital image analysis approach has been established to characterize and classify the cancer immune phenotypes, which might be utilized as predictive biomarkers for TGF β blockade therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

In this paper, we present a theoretical framework for design and analysis of distributed flocking algorithms. Two cases of flocking in free-space and presence of multiple obstacles are considered. We present three flocking algorithms: two for free-flocking and one for constrained flocking. A comprehensive analysis of the first two algorithms is provided. We demonstrate the first algorithm embodies all three rules of Reynolds. This is a formal approach to extraction of interaction rules that lead to the emergence of collective behavior. We show that the first algorithm generically leads to regular fragmentation, whereas the second and third algorithms both lead to flocking. A systematic method is provided for construction of cost functions (or collective potentials) for flocking. These collective potentials penalize deviation from a class of lattice-shape objects called [alpha]-lattices. We use a multi-species framework for construction of collective potentials that consist of flock-members, or [alpha]-agents, and virtual agents associated with [alpha]-agents called [beta]- and [gamma]-agents. We show that migration of flocks can be performed using a peer-to-peer network of agents, i.e., "flocks need no leaders." A "universal" definition of flocking for particle systems with similarities to Lyapunov stability is given. Several simulation results are provided that demonstrate performing 2-D and 3-D flocking, split/rejoin maneuver, and squeezing maneuver for hundreds of agents using the proposed algorithms. Index Terms--Consensus theory, distributed control, dynamic graphs, mobile sensor networks, networked autonomous vehicles, self-assembly of networks, self-organizing systems, swarms.

In this paper, we discuss consensus problems for networks of dynamic agents with fixed and switching topologies. We analyze three cases: 1) directed networks with fixed topology; 2) directed networks with switching topology; and 3) undirected networks with communication time-delays and fixed topology. We introduce two consensus protocols for networks with and without time-delays and provide a convergence analysis in all three cases. We establish a direct connection between the algebraic connectivity (or Fiedler eigenvalue) of the network and the performance (or negotiation speed) of a linear consensus protocol. This required the generalization of the notion of algebraic connectivity of undirected graphs to digraphs. It turns out that balanced digraphs play a key role in addressing average-consensus problems. We introduce disagreement functions for convergence analysis of consensus protocols. A disagreement function is a Lyapunov function for the disagreement network dynamics. We proposed a simple disagreement function that is a common Lyapunov function for the disagreement dynamics of a directed network with switching topology. A distinctive feature of this work is to address consensus problems for networks with directed information flow. We provide analytical tools that rely on algebraic graph theory, matrix theory, and control theory. Simulations are provided that demonstrate the effectiveness of our theoretical results. Index Terms--Algebraic graph theory, consensus problems, digraph theory, graph Laplacians, networks of autonomous agents, networks with time-delays, switching systems.

Complex geology and tectonics of the NW Iran, the Caucasus region, and Eastern Turkey, are responsible for the present‐day landscapes of the region. The Aras drainage basin located in Iran, Azerbaijan and Armenia borders, provides an appropriate geographical environment for systematically studying the landforms produced or modified by active tectonic processes. Several morphometric indices were calculated for 114 sub‐basins to assess relative tectonic activity levels. Results were evaluated using two different methods; Index of Active Tectonics (IAT) and Analytical Hierarchy Process (AHP) methods. IAT results show that 2% of the sub‐basins belong to very high, 25% to high, 46% to moderate and 27% to low tectonic activity classes. AHP results, display that 12% of the sub‐basins belong to very high, 25% to high, 43% to moderate, and 20% to low tectonic activity classes. Results of both methods show approximate consistency and indicate that the tectonic activity along the Aras drainage basin is moderate to high and decreases from southwest to the northwest which is probably due to terminating fault branches in young unconsolidated deposits or strain partitioning processes. The major fault zones (e.g., Aras, Pambak–Sevan–Sunik, Akera, and Moghan fault zones) include areas with very high and high tectonic activity classes. Accordingly, the uplift rates have been estimated as >0.5 mm/yr for central and western parts, whereas the uplift rates are relatively less in the eastern part (<0.5 mm/yr). The Aras fault zone includes five active structural segments that the main Aras and Horadiz segments of them show relatively higher tectonic activity. [ABSTRACT FROM AUTHOR]

In the recent years, enhanced functionality of treatment systems based on nanostructures has attracted a lot of interest. Photodynamic therapy (PDT) is one such treatment method. Here, the authors report the results of the investigations on synthesis and characterisation of gold nanoparticles (GNPs) and their application in PDT along with 5‐aminolevolenic acid (5‐ALA) (as photosensitiser) with no conjugation. Three sizes of GNPs were synthesised and their cytotoxicity was investigated by using MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay on epidermal carcinoma cell line. The results showed that the PDT efficiency of ALA increased in presence of GNPs. This effect was more considerable for 4 nm particles. [ABSTRACT FROM AUTHOR]

The application of rod‐shaped gold nanoparticles as probes and carriers in biological systems have recently attracted great interest. UV–vis spectroscopy, circular dichroism, Fourier transform infrared spectroscopy, scanning electron microscopy and atomic force microscopy were used to study optical and structural properties of rod‐shaped gold nanoparticles when interacting with DNA oligomers in phosphate sodium salt buffer. The morphological transformation process of rod‐shaped gold nanoparticles resulting from the interaction with single‐stranded DNA (ssDNA) showed the role of hexadecyltrimethylammonium bromide (CTAB) in nanostructures as the main interacting agent. The obtained results confirmed that the CTAB coat of rod‐shaped gold nanoparticles have powerful positive charges for conjugations with surface negative charges of phosphate groups on ssDNA oligomers. The CTAB also inhibit the formation of covalent sulphide bonds between the gold core of rod‐shaped nanoparticles and alkanethiol oligonucleotides. The authors found that when the nanorods were exposed to ssDNA oligonucleotides, the gold nanorods changed their shapes and sizes, and exposed some microscopic malformations which could be used in the development of colorimetric assays of nucleic acids. [ABSTRACT FROM AUTHOR]

Cauliflower-like DNAs are stem-loop DNAs that are fabricated periodically in inverted repetitions from deoxyribonucleic acid phosphates (dNTPs) by loop-mediated isothermal amplification (LAMP). Cauliflowerlike DNAs have ladder-shape behaviors on gel electrophoresis, and increasing the time of LAMP leads to multiplying the repetitions, stem-loops, and electrophoretic bands. Cauliflower-like DNAs were fabricated via LAMP using two loop primers, two bumper primers, dNTPs, a Α-phage DNA template, and a Bst DNA polymerase in 75- and 90-min periods. These times led to manufacturing two types of cauliflower-like DNAs with different contents of inverted repetitions and stem-loops, which were clearly indicated by two comparable electrophoresis patterns in agarose gel. LAMP-fabricated DNAs and natural dsB-DNA (salmon genomic DNA) were dialyzed in Gomori phosphate buffer (10 mM, pH 7.4) to be isolated from salts, nucleotides, and primers. DialyzedDNAswere studied usingUVspectroscopy, circular dichroism spectropolarimetry, and fluorescence spectrophotometry. Structural analyses indicated reduction of the molecular ellipticity and extinction coefficients in comparison with B-DNA. Also, cauliflower-like DNAs demonstrated less intrinsic and more extrinsic fluorescence in comparison with natural DNA. The overwinding and lengthening of the cauliflower-like configurations of LAMP DNAs led to changes in physical parameters of this type of DNA in comparison with natural DNA. The results obtained introduced new biomolecular characteristics ofDNAmacromolecules fabricated within aLAMPprocess and show the effects of more inverted repeats and stem-loops, which are manufactured by lengthening the process. [ABSTRACT FROM AUTHOR]

The aim of this study is to develop a nucleic acid sensor based on piezoelectric crystal microbalance system (QCM) for following hybridization. Piezoelectric quartz crystal surfaces were first treated in a glow–discharge apparatus with ethylene diamine (EDA) plasma at 15 W (discharge power), 2.5 min (incubation time) and 35 ml/min (monomer flow rate) to create amino groups on the crystal surfaces. The thickness of the EDA–plasma film formed was about 43±24 A˚. Then, the amino groups on the crystal surfaces were converted to aldehyde groups by reacting the amino groups with glutaraldehyde (GA) at different conditions. A GA concentration of 2.5% and an incubation time of 2 h were selected as optimal values at this step, corresponding to a GA surface concentration of about 270 ng/cm2. A double strand Oligonucleotides, having one extra base on 5′-end of one of the complementary strands, were immobilized through the amino groups of this base onto the GA-modified crystals. Optimal immobilization conditions were as follows: oligonucleotide concentration: 1 μg/ml; time: 3 h; pH: 9.2 carbonate buffer; ionic strength: 0.1; and temperature: 20 °C. The QCM sensor carrying the covalently bound strand was used in the hybridization experiments, which showed that equilibrium is achieved in about 5 min, and the frequency shift measured is related to the concentration of the target strand to be measured within the medium. [Copyright &y& Elsevier]

The aim of this study is to investigate complexation of metallothionein (MT) with cadmium and zinc ions. An oligopeptide (i.e. Lys-Cys-Thr-Cys-Cys-Ala), a fragment of MT was covalently immobilized onto piezoelectric crystals, which were first treated with ethylene diamine plasma in a glow-discharge apparatus, and then were chemically reacted with glutaraldehyde. Complexation of the immobilized MT with Zn(II) and Cd(II) ions in aqueous media was followed by recording the changes of the frequency shifts of the piezoelectric quartz crystals. The amount of Cd(II) ions interacted with the immobilized MT molecules was the highest at pH 7.4, and decreased with an increase in the pH of the medium, in parallel to the decrease in the amount of immobilized MT. The number of Zn(II) ions interacted with the immobilized MT molecules was higher than the number of Cd(II) ions when the adsorption was from solutions containing a single-metal ion with the same ion concentrations. In consecutive adsorption studies, we observed that the type of metal ions used in the first interaction is important. These experiments showed also that there is an exchange between the metal ions, and competition provokes adsorption of both ions due to synergistic–antagonistic effects. [Copyright &y& Elsevier]

The aim of this study is to develop an immunoaffinity sensor based on piezoelectric crystals for human serum albumin (HSA) detection in aqueous media. Quartz crystals were treated with ethylene diamine (EDA) plasma in a glow-discharge apparatus in order to substitute amino groups on their surfaces. Then anti-HSA antibodies were immobilized via these amino groups by using glutaraldehyde (GA) as cross-linker. Immobilization of the antibody on the quartz crystal was examined for different pH, antibody concentration and treatment time. The optimum conditions for anti-HSA immobilization were evaluated by the measurements of the activity of the surface against HSA. The optimum values of pH, antibody concentration and treatment time were found 6.2, 0.15 mg/ml and 2 h, respectively. For detection of HSA into the solution, two methods were used. In the first (dip and dry) method, the frequency shifts were measured in air after the 1 h interaction of the anti-HSA immobilized crystals with HSA solution. In the other (direct) method, the frequency shifts were followed continuously for 60 min. while the probe was immersed in the HSA solution. An increase for the frequency shifts was observed with increasing of HSA concentration of 16–128 μg/ml. Both the immobilization and antibody-interaction conditions were found important on the extend of these specific interaction. The relations between the HSA concentrations and frequency shifts were exponential in both methods. [Copyright &y& Elsevier]

The development of novel nanoparticles for diagnostic and therapeutic applications has been one of the most crucial challenges in cancer theranostics for the last decades. Herein, we functionalized iron oxide nanoparticles (IONPs) with the fourth generation (G4) of poly amidoamine (PAMAM) dendrimers (G4@IONPs) for magnetic hyperthermia treatment of breast cancer in Bagg albino strain C (BALB/c)mice. The survival of breast cancer cells significantly decreased after incubation with G4@IONPs and exposure to an alternating magnetic field (AMF) due to apoptosis and elevation of Bax (Bcl-2 associated X)/Bcl-2(B-cell lymphoma 2) ratio. After intratumoral injection of G4@IONPs, tumor-bearing BALB/c mice were exposed to AMF for 20 min; this procedure was repeated three times every other day. After the last treatment, tumor size was measured every three days. Histopathological and Immunohistochemical studies were performed on the liver, lung, and tumor tissues in treated and control mice. The results did not show any metastatic cells in the liver and lung tissues in the treatment group, while the control mice tissues contained metastatic breast cancer cells. Furthermore, the findings of the present study showed that magnetic hyperthermia treatment inhibited tumor growth by increasing cancer cell apoptosis, as well as reducing the tumor angiogenesis. [ABSTRACT FROM AUTHOR]

Objective: In recently air pollution is motivated by many agents and in the aerosol we can distinguish smallest airways, composed by biological particles, such as pollen grains and particulate of anthropogenic origin. During the last decade the size, shape, composition, sources and effect of these particle matters (PM) on human health have been studied by microscopic methods. Atomic force microscopy (AFM) is therefore a valuable complementary microscopy technique for the comparative study of the pollen grains surface morphology. The main goals of this research we investigated to characterize the elemental differences in the composition of the airborne ash pollen exine wall and to describe the particulate matter found adhered to this pollen in the Tehran, capital city of Iran, using an Energy Dispersive X-Ray analysis (EDX) on the SEM and Atomic force microscopy (AFM). Material and Methods: The first stage, pollen grains were collected in pollutant area (Tehran regions) and nonpollutant area (Parand city near the Tehran).Then used SEM/EDX for pollen grains analysis and advantages of two samples for AFM for the imaging of reside in the sticky PM on the ash pollen surface of the high spatial resolution, compared with SEM images, and the unique three-dimensional rendition of the exine surface topography, which avoids cross sectioning of the samples. Results: Images showed of exine units from the tectum of polluted and non- polluted pollen were done by AFM. These units of polluted sample showed were recorded adhered the PM in exine surface as being 250 to 300nm wide. This particle matter size is lower than PM2.5. We have obtained atomically resolved images on single aerosol particles in Tehran at the first on environmental biological samples. Conclusion: Our results showed AFM images method can be used for identifying pollen surface contamination and evaluation of PM size more exact and showed good agreement with light and electron microscopy micrographs. [ABSTRACT FROM AUTHOR]

In the current study, we report on the design and development of a novel electrochemical immunosensor for the detection of cancer antigen 125 (CA125) oncomarker. Polyamidoamine/gold nanoparticles (PAMAM/AuNPs) were used to increase the conductivity and enhance the number of antibodies (Abs) immobilized on the electrode surface. Three-dimensional reduced graphene oxide-multiwall carbon nanotubes (3DrGO-MWCNTs) were used to modify the glassy carbon electrode to improve the electrode conductivity and specific surface area. Ab and toluidine blue attached to O -succinyl-chitosan-magnetic nanoparticles (Suc-CS@MNPs) as a tracer. The poor solubility of chitosan (CS) was improved by succinic anhydride using a novel modification method. Under optimum condition, the developed immunosensor exhibited a wide linear range (0.0005–75 U/mL) and an excellent limit of detection around 6 μU/mL. The reliability of the engineered immunosensor in detecting CA125 was verified by standard addition recovery method, which was further compared to enzyme-linked immunosorbent assay (ELISA). The proposed immunosensor exhibited excellent stability, high selectivity and sensitivity, and good reproducibility. Based on the great performance of the engineered immunosensor, it is proposed as a robust and reliable diagnostic tool for the detection of CA125 in the clinic. Image 1 • An immunosensor was developed for detecting CA125 with a wide linear range (0.0005–75 U/mL) and an excellent LOD (6 μU/mL). • PAMAM/AuNPs were synthesized through a one-step method using PAMAM as a stabilizing and reducing agent. • Chitosan water solubility in natural pH was increased using a novel modification method. • Succinyl-chitosan-coated magnetic nanoparticles were synthesized with good dispersity and high surface functional groups. [ABSTRACT FROM AUTHOR]

• Use of reduced graphene oxide as a photothermal label for lateral flow assay. • Reduced graphene oxide shows higher photothermal properties than graphene oxide. • Sensitivity improvement of a lateral flow assay by photothermal quantification. Lateral flow immunoassay (LFA) is a well-known point-of-care technology for the detection of various analytes. However, low sensitivity and lack of quantitative results are some of its critical drawbacks. Here we report a photothermal enhanced lateral flow sensor on the basis of the photothermal properties of reduced graphene oxide (rGO) for the detection of E-coli O157:H7 as a model pathogen. The calibration curve of the photothermal method exhibited a linear range from 5 × 10⁵ to 5 × 10⁷ CFU/ml with a correlation coefficient of R2 = 0.96 and a regression equation of y = 8.1x-43 for standard bacteria solutions in phosphate buffer. The limit of detection was ∼5 × 10⁵ CFU/ml for standard bacteria solutions, which was a 10-fold enhancement in sensitivity compared to the qualitative results. Specificity experiments showed that the photothermal method can only detect the target bacteria among 6 types of bacteria strains. It was confirmed that the developed technique could be a highly potential method for the rapid detection field because it can provide fast quantitative results with improved sensitivity. [ABSTRACT FROM AUTHOR]

Motivation: A protein can be represented in several forms, including its 1D sequence, 3D atom coordinates, and molecular surface. A protein surface contains rich structural and chemical features directly related to the protein's function such as its ability to interact with other molecules. While many methods have been developed for comparing the similarity of proteins using the sequence and structural representations, computational methods based on molecular surface representation are limited., Results: Here, we describe "Surface ID," a geometric deep learning system for high-throughput surface comparison based on geometric and chemical features. Surface ID offers a novel grouping and alignment algorithm useful for clustering proteins by function, visualization, and in silico screening of potential binding partners to a target molecule. Our method demonstrates top performance in surface similarity assessment, indicating great potential for protein functional annotation, a major need in protein engineering and therapeutic design., Availability and Implementation: Source code for the Surface ID model, trained weights, and inference script are available at https://github.com/Sanofi-Public/LMR-SurfaceID., (© The Author(s) 2023. Published by Oxford University Press.)

Most cell-cell interactions and crosstalks are mediated by ligand-receptor interactions. The advent of single-cell RNA-sequencing (scRNA-seq) techniques has enabled characterizing tissue heterogeneity at single-cell level. In the past few years, several methods have been developed to study ligand-receptor interactions at cell type level using scRNA-seq data. However, there is still no easy way to query the activity of a specific user-defined signaling pathway in a targeted way or to map the interactions of the same subunit with different ligands as part of different receptor complexes. Here, we present DiSiR, a fast and easy-to-use permutation-based software framework to investigate how individual cells are interacting with each other by analyzing signaling pathways of multi-subunit ligand-activated receptors from scRNA-seq data, not only for available curated databases of ligand-receptor interactions, but also for interactions that are not listed in these databases. We show that, when utilized to infer ligand-receptor interactions from both simulated and real datasets, DiSiR outperforms other well-known permutation-based methods, e.g. CellPhoneDB and ICELLNET. Finally, to demonstrate DiSiR's utility in exploring data and generating biologically relevant hypotheses, we apply it to COVID lung and rheumatoid arthritis (RA) synovium scRNA-seq datasets and highlight potential differences between inflammatory pathways at cell type level for control versus disease samples., (© The Author(s) 2023. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)

Increasing evidence suggests that the presence and spatial localization and distribution pattern of tumor infiltrating lymphocytes (TILs) is associate with response to immunotherapies. Recent studies have identified TGF β activity and signaling as a determinant of T cell exclusion in the tumor microenvironment and poor response to PD-1/PD-L1 blockade. Here we coupled the artificial intelligence (AI)-powered digital image analysis and gene expression profiling as an integrative approach to quantify distribution of TILs and characterize the associated TGF β pathway activity. Analysis of T cell spatial distribution in the solid tumor biopsies revealed substantial differences in the distribution patterns. The digital image analysis approach achieves 74% concordance with the pathologist assessment for tumor-immune phenotypes. The transcriptomic profiling suggests that the TIL score was negatively correlated with TGF β pathway activation, together with elevated TGF β signaling activity observed in excluded and desert tumor phenotypes. The present results demonstrate that the automated digital pathology algorithm for quantitative analysis of CD8 immunohistochemistry image can successfully assign the tumor into one of three infiltration phenotypes: immune desert, immune excluded or immune inflamed. The association between "cold" tumor-immune phenotypes and TGF β signature further demonstrates their potential as predictive biomarkers to identify appropriate patients that may benefit from TGF β blockade., (© 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Multiple methods have recently been developed to reconstruct full-length B-cell receptors (BCRs) from single-cell RNA sequencing (scRNA-seq) data. This need emerged from the expansion of scRNA-seq techniques, the increasing interest in antibody-based drug development and the importance of BCR repertoire changes in cancer and autoimmune disease progression. However, a comprehensive assessment of performance-influencing factors such as the sequencing depth, read length or number of somatic hypermutations (SHMs) as well as guidance regarding the choice of methodology is still lacking. In this work, we evaluated the ability of six available methods to reconstruct full-length BCRs using one simulated and three experimental SMART-seq datasets. In addition, we validated that the BCRs assembled in silico recognize their intended targets when expressed as monoclonal antibodies. We observed that methods such as BALDR, BASIC and BRACER showed the best overall performance across the tested datasets and conditions, whereas only BASIC demonstrated acceptable results on very short read libraries. Furthermore, the de novo assembly-based methods BRACER and BALDR were the most accurate in reconstructing BCRs harboring different degrees of SHMs in the variable domain, while TRUST4, MiXCR and BASIC were the fastest. Finally, we propose guidelines to select the best method based on the given data characteristics., (© The Author(s) 2022. Published by Oxford University Press on behalf of NAR Genomics and Bioinformatics.)

As the COVID-19 pandemic continues to spread, hundreds of new initiatives including studies on existing medicines are running to fight the disease. To deliver a potentially immediate and lasting treatment to current and emerging SARS-CoV-2 variants, new collaborations and ways of sharing are required to create as many paths forward as possible. Here, we leverage our expertise in computational antibody engineering to rationally design/engineer three previously reported SARS-CoV neutralizing antibodies and share our proposal towards anti-SARS-CoV-2 biologics therapeutics. SARS-CoV neutralizing antibodies, m396, 80R and CR-3022 were chosen as templates due to their diversified epitopes and confirmed neutralization potency against SARS-CoV (but not SARS-CoV-2 except for CR3022). Structures of variable fragment (Fv) in complex with receptor binding domain (RBD) from SARS-CoV or SARS-CoV-2 were subjected to our established in silico antibody engineering platform to improve their binding affinity to SARS-CoV-2 and developability profiles. The selected top mutations were ensembled into a focused library for each antibody for further screening. In addition, we convert the selected binders with different epitopes into the trispecific format, aiming to increase potency and to prevent mutational escape. Lastly, to avoid antibody-induced virus activation or enhancement, we suggest application of NNAS and DQ mutations to the Fc region to eliminate effector functions and extend half-life., (© The Author(s) 2021. Published by Oxford University Press on behalf of Antibody Therapeutics. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)