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Cerenkov luminescence imaging (CLI) is a promising approach to image-guided surgery and pathological sampling. It could offer additional advantages when combined to whole-body isotope tomographies. We aimed to obtain evidence of its applicability in lymphoma patho-diagnostics, thus we decided to investigate the radiodiagnostic potential of combined PET or SPECT/CLI in an experimental, novel spontaneous high-grade B-cell lymphoma mouse model (Bc.DLFL1). We monitored the lymphoma dissemination at early stage, and at clinically relevant stages such as advanced stage and terminal stage with in vivo 2-deoxy-2-[ 18 F]fluoro- d -glucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) and 67 Ga-citrate single photon emission computed tomography (SPECT)/MRI. In vivo imaging was combined with ex vivo high resolution CLI. The use of CLI with 18 F-Fluorine (F-18) and 67 Ga-Gallium isotopes in the selection of infiltrated lymph nodes for tumor staging and pathology was thus tested. At advanced stage, FDG PET/MRI plus ex vivo CLI allowed accurate detection of FDG accumulation in lymphoma-infiltrated tissues. At terminal stage we detected tumorous lymph nodes with SPECT/MRI and we could report in vivo detection of the Cerenkov light emission of 67 Ga. CLI with 67 Ga-citrate revealed lymphoma accumulation in distant lymph node locations, unnoticeable with only MRI. Flow cytometry and immunohistochemistry confirmed these imaging results. Our study promotes the combined use of PET and CLI in preclinical studies and clinical practice. Heterogeneous FDG distribution in lymph nodes, detected at sampling surgery, has implications for tissue pathology processing and it could direct therapy. The results with 67 Ga also point to the opportunities to further apply suitable SPECT radiopharmaceuticals for CLI.

Background/Objectives: The ongoing COVID-19 pandemic has underscored the need for alternative prophylactic measures, particularly for populations for whom vaccines may not be effective or accessible. This study aims to evaluate the efficacy of intranasally administered IgY antibodies derived from hen egg yolks as a protective agent against SARS-CoV-2 infection in Syrian golden hamsters, a well-established animal model for COVID-19. Methods: Hens were immunized with the spike protein of SARS-CoV-2 to generate IgY antibodies. These antibodies were extracted from the egg yolks, purified, and their neutralizing activity was tested in vitro. Syrian golden hamsters were then treated with the IgY antibodies before being challenged with SARS-CoV-2. Viral loads were quantified using droplet digital PCR (ddPCR), and lung pathology was assessed through histopathological analysis. Results: The in vitro assays showed that IgY effectively neutralized SARS-CoV-2. In the in vivo hamster model, IgY treatment led to a significant reduction in viral loads and a marked decrease in lung consolidation and inflammation compared to the positive control group. Histopathological findings further supported the protective role of IgY in reducing lung damage caused by SARS-CoV-2. Conclusions: The results demonstrate that IgY antibodies exhibit strong antiviral activity and can significantly reduce SARS-CoV-2 viral loads and associated lung pathology in hamsters. These findings suggest that IgY could be a viable prophylactic option for preventing SARS-CoV-2 infection, particularly for individuals who cannot receive or respond to vaccines. Further studies are warranted to optimize dosage and explore the long-term efficacy of IgY antibodies.

The aerodynamic performance of blade profiles critically influences the overall efficiency and operational stability of compressors and fans in modern aeroengines. This paper develops a multi-objective optimization framework for compressor/fan blade profiles by integrating the NSGA-III evolutionary algorithm with Multilayer Perceptron (MLP) surrogate modelling. Within this framework, the baseline profile is first parameterized, and Design of Experiments (DoE) is employed to sample the design space systematically. A high-accuracy MLP surrogate model is then trained to evaluate the aerodynamic performance during the NSGA-III optimization process efficiently. The Technique For Order of Preference by Similarity to Ideal Solution (TOPSIS) enables the optimal selection of a compromise solution from the generated Pareto front. An actual profile optimization case was used to verify the effectiveness of the proposed method. Under the constraints of fixed design incidence and flow turning angle, the optimized profile showed improvements in both loss and operating range, demonstrating that the proposed method can rapidly perform optimal profile design within the given aerodynamic constraints.

In the field of turbomachinery engineering design, profile design is a complex process highly dependent on iterative optimization, often requiring the experience of human designers to repeatedly adjust the profile shape to meet requirements. Aiming at the need to directly generate shapes that satisfy target specifications in practice, the conditional Generative Adversarial Network (cGAN) demonstrates unique advantages by its data-driven direct design synthesis capability. This paper proposes a data-driven inverse aerodynamic design method for blade profiles based on cGAN and Multilayer Perceptron (MLP). In this method, MLP is utilized to learn the mapping from design parameters to performance parameters. By associating profile design parameters with precomputed aerodynamic performance, a cGAN is employed to learn to generate geometries that meet the specified aerodynamic performance. MLP is also used to provide the dataset for training the cGAN and to test the generation capability of the cGAN. Subsonic design validation confirms that the trained cGAN generator can directly produce profile geometries meeting the specified performance target, eliminating complex iterations and significantly reducing design time, thereby substantially boosting design efficiency.

Following the entry of pathogens through skin or mucosal surfaces as first line of defense, during their propagation the pathogens are transported by various immune cells to the nearby secondary lymphoid organs, such as lymph nodes or Peyer's patches (1). Here, the lymphoid architecture allows for the efficient communication and cooperation between various leukocytes, despite their compartmentalization into different domains, including follicles (B-cell zones) and neighboring T-cell dominated regions. The recognition of antigens elicits different types of immune reactions, often resulting in the transformation of resting follicles into secondary follicles harboring germinal centers (2).Generally, secondary lymphoid organs, such as spleen, lymph nodes and programmed intestinal lymphoid tissues, including Peyer’s patches and mesenteric lymph nodes, start to develop before birth (3); however, there is another branch of the lymphoid structure that plays role in the local immunological challenges under the mucosa, such as cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Their development is initiated after birth (4), allowing the expanded immunological surveillance of the mucosal surface of the intestines, continuously exposed to alimentary and microbial antigens. In contrast to these well-studied lymphoid tissues, the role of serosa in the immune system has not been fully investigated. Although substantially lesser surface compared to the mucosal area, the serosa nevertheless represents a considerably large surface shared by various abdominal organs, often in a close arrangement with adipose tissue, and harboring a unique immunological compartment including a large number of B-1 B cells (5).Adipose tissue is usually considered as a vital energy storage. However, recent studies have unveiled the immunological potentials of adipose-associated lymphoid structures, which play essential roles in the local immune response (6–8), where they typically appear in diffuse forms and are embedded into the adipose components (9). Adipose tissue contains various lymphoid territories which participate in the local immunological challenge (6, 7). Visceral fat contains numerous leukocytes, which form adipose-associated lymphoid organoids. Here the focal accumulation of leukocytes is promoted by chemokines CXCL1 and CXCL13 (8).Typically they appear in diffuse forms and are embedded into the adipose (9). As prototypic adipose tissue containing lymphoid congregates, the omentum has been considered the main guardian in the abdominal cavity for a long time (10). The milky spots (MSs) on the surface of the omentum contain various leukocytes with an extensive capillary meshwork (11–13), where B-1 cells are the major source of natural antibodies (14). Even though there is no evidence of germinal centers or follicular dendritic cells (FDCs), T-dependent humoral immune responses can also occur in the MSs (15, 16). More recently, fat-associated lymphoid clusters (FALCs) were discovered in the mesenteric fat and at other visceral locations (17–19). They contain B cells, T cells, macrophages, and other innate lymphoid cells including ILC2, which promote B1 cell proliferation (17, 18). (Fig. 1).B cells are essential elements of adaptive immunity in the body. Eventually, they will secret antibodies and differentiate into plasma cells or long-lived memory B cells (20–23). Besides that, B cells are also able to regulate immune functions through cytokine production (24, 25). Following extensive research on their developmental and differentiation characteristics, B cells are now divided into several subsets according to the cell surface markers, transcription factor specifications and immunological functions. B-1 lymphocytes promote innate-like immune response typically with natural antibodies production, and B-2 cells with regulatory activities or antigen presentation, in addition to antigen recognition (26, 27). During these processes, various activation status-related and position-related (resting or activated; in follicles mantle zone or germinal center-located, or within germinal center, light zone or dark zone located, respectively) subsets can be distinguished. As two main products, either memory B cells or plasma cells may form. Importantly, the various lymphoid tissue locations confer distinct microenvironmental cues for B-cell subset survival and commitment, thus affecting the differentiation and specialization, including Ig isotype switch, short-term or long-term plasmablast differentiation.

Bc-DLFL.1 is a novel spontaneous, high-grade transplantable mouse B-cell lymphoma model for selective serosal propagation. These cells attach to the omentum and mesentery and show dissemination in mesenteric lymph nodes. We aimed to investigate its early stage spread at one day post-intraperitoneal inoculation of lymphoma cells (n = 18 mice), and its advanced stage at seven days post-inoculation with in vivo [18F]FDG-PET and [18F]PET/MRI, and ex vivo by autoradiography and Cherenkov luminescence imaging (CLI). Of the early stage group, nine animals received intraperitoneal injections, and nine received intravenous [18F]FDG injections. The advanced stage group (n = 3) received intravenous FDG injections. In the early stage, using autoradiography we observed a marked accumulation in the mesentery after intraperitoneal FDG injection. Using other imaging methods and autoradiography, following the intravenous injection of FDG no accumulations were detected. At the advanced stage, tracer accumulation was clearly detected in mesenteric lymph nodes and in the peritoneum after intravenous administration using PET. We confirmed the results with immunohistochemistry. Our results in this model highlight the importance of local FDG administration during diagnostic imaging to precisely assess early peritoneal manifestations of other malignancies (colon, stomach, ovary). These findings also support the importance of applying topical therapies, in addition to systemic treatments in peritoneal cancer spread.

α particles must be monitored to be managed as radioactive diagnostic agents or nuclear activity indicators. The new generation of perovskite detectors suffer from limited energy resolution, which affects spectroscopy and imaging applications. Here, we report that the solution-grown CsPbBr 3 crystal exhibits a low and stable dark current (34.6 nA·cm −2 at 200 V) by thinning the as-grown crystal to decrease the high concentration CsPb 2 Br 5 phase near the surface. The introduction of the Schottky electrode for the CsPbBr 3 detector further reduces the dark current and improves the high-temperature stability. An energy resolution of 6.9% is achieved with the commercial electronic system, while the effects of air scattering and absorption are investigated. Moreover, 1.1% energy resolution is recognized by a full-customized readout application-specific integrated circuit without any additional signal processing, which matches well with the given parameters of the CsPbBr 3 detector by reducing the parasitic capacitance and electronic noise. By developing a synergistic strategy of thinning the perovskite crystal, employing Schottky electrode and full-customised readout application specific integrated circuit to supress dark current and electronic noise, the authors report an energy resolution of 1.1% for perovskite α-particle detector.

The spread of coronavirus disease 2019 (COVID‐19), caused by severe respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has progressed into a global pandemic. To date, thousands of genetic variants have been identified among SARS‐CoV‐2 isolates collected from patients. Sequence analysis reveals that the codon adaptation index (CAI) values of viral sequences have decreased over time but with occasional fluctuations. Through evolution modeling, it is found that this phenomenon may result from the virus's mutation preference during transmission. Using dual‐luciferase assays, it is further discovered that the deoptimization of codons in the viral sequence may weaken protein expression during virus evolution, indicating that codon usage may play an important role in virus fitness. Finally, given the importance of codon usage in protein expression and particularly for mRNA vaccines, it is designed several codon‐optimized Omicron BA.2.12.1, BA.4/5, and XBB.1.5 spike mRNA vaccine candidates and experimentally validated their high levels of expression. This study highlights the importance of codon usage in virus evolution and provides guidelines for codon optimization in mRNA and DNA vaccine development. This study reveals that SARS‐CoV‐2 tends to use nonoptimal human codons, displaying a decreasing codon adaptation index over time. Experiments show that synonymous mutations significantly impact viral protein expression, potentially affecting SARS‐CoV‐2 fitness. Researchers design and validate codon‐optimized spike mRNA vaccine candidates for Omicron BA.2.12.1, BA.4/5, and XBB.1.5 variants, which could contribute to more effective vaccines against SARS‐CoV‐2 variants.

Pure-organic semiconductors have attracted broad interest in tissue-equivalent and biocompatible X-ray sensors, while their low-dose X-ray imaging capability still suffers from poor charge transport properties. Here, we report a dimensionality tailoring method to enhance hole transport in pure-organic semiconductors, enabling highly stable and low-dose X-ray detection and imaging without toxic elements such as Pb or Hg. By substituting the -CN group in 4-hydroxycyanobenzene (4HCB, HO-C 6 H 4 -CN) with a -COOCH 3 group, we transform the two-dimensional (2D) structure into a three-dimensional (3D) 4-methyl hydroxybenzoate (4MHB, HO-C 6 H 4 -COOCH 3 ) crystal featuring enhanced intermolecular π-π stacking. This structural reconfiguration yields a high hole mobility of 19.91 cm 2  V −1 s −1 and an ultralow dark current drift of 1.14 × 10 −10  nA cm −1 s −1 V −1 at 100 V mm −1 . The superior charge transport facilitated by stronger π-π interactions enables stable X-ray detection with a detection limit as low as 4.22 nGy air s −1 and high-resolution imaging at 1.6 lp mm −1 under low-dose irradiation (58.76 μGy air s −1 ). This work demonstrates a molecular tailoring strategy to modulate the structural dimensionality and the charge transport path of pure-organic semiconductors, advancing tissue-equivalence and biocompatible X-ray imagers toward high-resolution and low-dose operation. The charge transport properties of organic semiconductors limit their low-dose X-ray imaging capability. Here, authors report 3D 4-methyl hydroxybenzoate for enhanced π-π stacking, achieving stable X-ray detection with detection limit of 4.22 nGy air s −1 and high-resolution imaging at 1.6 lp mm −1 .

Although reports of human infection with influenza A(H5N6) increased in 2021, reports of similar H5N6 virus infection in poultry are few. We detected 10 avian influenza A(H5N6) clade 2.3.4.4b viruses in poultry from 4 provinces in China. The viruses showed strong immune-escape capacity and complex genetic reassortment, suggesting further transmission risk.