Scattered crypt intestinal epithelial cell apoptosis induces necrotizing enterocolitis via intricate mechanisms.

BACKGROUND & AIMS: Necrotizing enterocolitis (NEC) is a life-threatening disease affecting mostly the ileum of preemies. Intestinal epithelial cell (IEC) apoptosis contributes to NEC pathogenesis. However, how scattered crypt IEC apoptosis leads to NEC with excessive villus epithelial necrosis remains unclear. METHODS: A novel triple-transgenic mouse model, namely, 3xTg-iAPcIEC (inducible apoptosis phenotype in crypt-IEC), was developed to induce IECs-specific overexpression of Fasl transgene using doxycycline (Dox)-inducible tetO-rtTA system and villin-cre technology. The three days old neonatal 3xTg-iAPcIEC mice and their littermate controls were subcutaneously (s.c.) challenged with a single dose of Dox. Intestinal tissues were processed at different time points to examine scattered crypt IEC apoptosis-mediated NEC development. Gene knockout technology, antibody-mediated cell depletion, and antibiotic-facilitated Gram-positive bacteria depletion were used to study mechanisms. RESULTS: Treatment of 3xTg-iAPcIEC mouse pups with Dox induces scattered crypt IEC apoptosis followed by crypt inflammation and excessive villous necrosis resembling NEC. This progression correlated with elevated Ifng, Rip3, CD8+ T cells, and Gram-positive bacteria in the ileum. Mechanistically, IFN-γ and RIP3-activated signals mediate the effect of scattered crypt IEC apoptosis on the induction of intestinal crypt inflammation and villous necrosis. Meanwhile, pathophysiological events of CD8+ T cell infiltration and dysbiosis with Gram-positive bacteria primarily contribute to excessive villous inflammation and necrosis. Notably, blocking any of these events protects against NEC development in 3xTg-iAPcIEC mouse pups, underlining their central roles in NEC pathogenesis. CONCLUSIONS: Scattered crypt IEC apoptosis induces NEC in mouse pups via IFN-γ, RIP3, CD8+ T cells, and Gram-positive bacteria-mediated comprehensive pathophysiological events. Our findings may advance knowledge in the prevention and treatment of NEC.

Metabolic immaturity of newborns and breast milk bile acid metabolites are the central determinants of heightened neonatal vulnerability to norovirus diarrhea.

Noroviruses are the leading global cause of acute gastroenteritis, responsible for 685 million annual cases. While all age groups are susceptible to noroviruses, children are vulnerable to more severe infections than adults, underscored by 200 million pediatric cases and up to 200,000 deaths in children annually. Understanding the basis for the increased vulnerability of young hosts is critical to developing effective treatments. The pathogenic outcome of any enteric virus infection is governed by a complex interplay between the virus, intestinal microbiota, and host immune factors. A central mediator in these complex relationships are host- and microbiota-derived metabolites. Noroviruses bind a specific class of metabolites, bile acids, which are produced by the host and then modified by commensal bacterial enzymes. Paradoxically, bile acids can have both proviral and antiviral roles during norovirus infections. Considering these opposing effects, the microbiota-regulated balance of the bile acid pool may be a key determinant of the pathogenic outcome of a norovirus infection. The bile acid pool in newborns is unique due to immaturity of host metabolic pathways and developing gut microbiota, which could underlie the vulnerability of these hosts to severe norovirus infections. Supporting this concept, we demonstrate herein that microbiota and their bile acid metabolites protect from severe norovirus diarrhea whereas host-derived bile acids promote disease. Remarkably, we also report that maternal bile acid metabolism determines neonatal susceptibility to norovirus diarrhea during breastfeeding by delivering proviral bile acids to the newborn. Finally, directed targeting of maternal and neonatal bile acid metabolism can protect the neonatal host from norovirus disease. Altogether, these data support the conclusion that metabolic immaturity in newborns and ingestion of proviral maternal metabolites in breast milk are the central determinants of heightened neonatal vulnerability to norovirus disease.

Recombinant IGF-1/BP3 protects against intestinal injury in a neonatal mouse NEC model.

BACKGROUND: Recombinant human IGF-1/binding protein-3 (rhIGF-1/BP3) is currently being tested in phase II clinical trials in premature infants to prevent bronchopulmonary dysplasia, but its impact on the neonatal intestine remains unclear. The aim of this study was to determine whether rhIGF-1/BP3 protects against necrotizing enterocolitis (NEC) in mice and to investigate the mechanisms involved. METHODS: Neonatal mice were dam fed or injected intraperitoneally with rhIGF-1/BP3 (or vehicle) and submitted to an experimental NEC model. Serum IGF-1 was assessed by ELISA and intestinal vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) expression by Western blot. Intestinal endothelial cell proliferation, and enterocyte proliferation and migration were examined by immunofluorescence. Pup survival and histological intestinal injury were determined. RESULTS: In pups exposed to experimental NEC, serum IBP3-bound IGF-1 level was decreased. Exogenous rhIGF-1/BP3 preserved VEGF and VEGFR2 protein expression, decreased vascular permeability, and preserved endothelial cell proliferation in the small intestine. Furthermore, rhIGF-1/BP3 promoted enterocyte proliferation and migration, which effects were attenuated by inhibiting VEGFR2 signaling, decreased enterocyte apoptosis and decreased systemic and intestinal inflammation. rhIGF-1/BP3 improved survival and reduced the incidence of severe intestinal injury in experimental NEC. CONCLUSIONS: Exogenous rhIGF-1/BP3 protects neonatal mice against experimental NEC via multiple mechanisms. IMPACT: Exogenous rhIGF-1/BP3 preserves intestinal microvascular development and integrity, promotes enterocyte proliferation and migration, decreases local and systemic inflammation, and protects neonatal mice against NEC. The article adds pre-clinical evidence of a protective role for rhIGF-1/BP3 on the premature gut. It provides evidence supporting the use of rhIGF1/BP3 in premature neonates to protect against NEC.

Phase retrieval based on deep learning with bandpass filtering in holographic data storage.

A phase retrieval method based on deep learning with bandpass filtering in holographic data storage is proposed. The relationship between the known encoded data pages and their near-field diffraction intensity patterns is established by an end-to-end convolutional neural network, which is used to predict the unknown phase data page. We found the training efficiency of phase retrieval by deep learning is mainly determined by the edge details of the adjacent phase codes, which are the high-frequency components of the phase code. Therefore, we can attenuate the low-frequency components to reduce material consumption. Besides, we also filter out the high-order frequency over twice Nyquist size, which is redundant information with poor anti-noise performance. Compared with full-frequency recording, the consumption of storage media is reduced by 2.94 times, thus improving the storage density.

Highly sensitive and repeatable recording photopolymer for holographic data storage containing N-methylpyrrolidone.

The low photosensitivity of phenanthraquinone-doped poly(methyl methacrylate) (PQ/PMMA) severely limits its recording speed for holographic data storage. A high-performance holographic recording medium based on a unique combination of N-methylpyrrolidone (NMP) regulated PQ/PMMA has been developed. A NMP-PQ/PMMA photopolymer with high sensitivity, high diffraction efficiency and negligible volume shrinkage was successfully fabricated by tuning the composition of the PMMA matrix by varying the ratio of NMP to monomers. The photosensitivity is increased by 6.9 times (from 0.27 cm J-1 to 1.86 cm J-1), the diffraction efficiency is increased from 60% to > 80%, and volume shrinkage is decreased by a factor of 2 (from 0.4% to 0.2%). Further investigation revealed that the addition of NMP significantly reduced the molecular weight of PMMA and increased the amount of MMA residuals, while also improving the solubility of PQ molecules. More interestingly, for the first time, the NMP-PQ/PMMA material could record data information repeatedly at least 6 times. The present study elucidates that the introduction of NMP not only modulates the molecular weight of PMMA but also enables the residual monomer MMA to more easily combine with PQ to form a photoproduct for improved holographic performance.

Phase retrieval in holographic data storage by expanded spectrum combined with dynamic sampling method.

Phase retrieval in holographic data storage by expanded spectrum combined with dynamic sampling method is proposed, which serves to both reduce media consumption and to shorten the iterative number of phase code retrieval. Generally, high-fidelity phase retrieval requires twice Nyquist frequency in phase-modulated holographic data storage. To increase storage density, we only recorded and captured the signal with Nyquist size and used the frequency expanded method to realize high-fidelity phase retrieval. In the decoding process, the iterative Fourier transform algorithm is used to retrieve the phase information of the reconstructed beam. The expanded spectrum is dynamically sampled, which can provide a faster convergence path for the phase retrieval. We aimed to demonstrate the possibility of integrating various methods on the Fourier domain and providing a potential way to improve the performance of holographic data storage systems. The simulation and experimental results proved the combination of processing methods in frequency spectrum was benefit.

Modulating microbiome-immune axis in the deployment-related chronic diseases of Veterans: report of an expert meeting.

The present report summarizes the United States Department of Veterans Affairs (VA) field-based meeting titled "Modulating microbiome-immune axis in the deployment-related chronic diseases of Veterans." Our Veteran patient population experiences a high incidence of service-related chronic physical and mental health problems, such as infection, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), various forms of hematological and non-hematological malignancies, neurologic conditions, end-stage organ failure, requiring transplantation, and posttraumatic stress disorder (PTSD). We report the views of a group of scientists who focus on the current state of scientific knowledge elucidating the mechanisms underlying the aforementioned disorders, novel therapeutic targets, and development of new approaches for clinical intervention. In conclusion, we dovetailed on four research areas of interest: 1) microbiome interaction with immune cells after hematopoietic cell and/or solid organ transplantation, graft-versus-host disease (GVHD) and graft rejection, 2) intestinal inflammation and its modification in IBD and cancer, 3) microbiome-neuron-immunity interplay in mental and physical health, and 4) microbiome-micronutrient-immune interactions during homeostasis and infectious diseases. At this VA field-based meeting, we proposed to explore a multi-disciplinary, multi-institutional, collaborative strategy to initiate a roadmap, specifically focusing on host microbiome-immune interactions among those with service-related chronic diseases to potentially identify novel and translatable therapeutic targets.

Scalar vortex beams produced by Pancharatnam-Berry phase optical elements that utilize polarization holography.

We discuss the appearance of the Pancharatnam-Berry phase in polarization holography, and confirm the possibility of generating scalar vortex beams by using the Pancharatnam-Berry phase. The polarization holograms used to generate scalar vortex beams are produced in phenanthrenequinone-doped polymethylmethacrylate (PQ/PMMA), where each radial direction consists of an equivalent half-wave plate hologram with gradually changing directions. The spin angular momentum carried by a circular polarization reading wave is converted into orbital angular momentum in a reconstruction process, resulting in the formation of scalar vortex beams with positive and negative topological charges controlled by the reading polarization.

B Cell Lymphocytosis in Juvenile Dermatomyositis.

In this study, we determined if B lymphocytosis may serve as a JDM biomarker for disease activity. Children with untreated JDM were divided into two groups based on age-adjusted B cell percentage (determined through flow cytometry): 90 JDM in the normal B cell group and 45 in the high B cell group. We compared through T-testing the age, sex, ethnicity, duration of untreated disease (DUD), disease activity scores for skin (sDAS), muscle (mDAS), total (tDAS), CMAS, and neopterin between these two groups. The patients in the high B cell group had a higher tDAS (p = 0.009), mDAS (p = 0.021), and neopterin (p = 0.0365). Secondary analyses included B cell values over time and BAFF levels in matched patients with JM (juvenile myositis) and concurrent interstitial lung disease (ILD); JM alone and healthy controls Patient B cell percentage and number was significantly higher after 3-6 months of therapy and then significantly lower on completion of therapy (p =< 0.0001). The JM groups had higher BAFF levels than controls 1304 vs. 692 ng/mL (p = 0.0124). This study supports B cell lymphocytosis as a JDM disease-activity biomarker and bolsters the basis for B cell-directed therapies in JDM.

Polarization splitters with designable separation angles based on polarization holography of tensor theory.

We propose a simple and inexpensive method for the fabrication of polarization splitters with designable separation angles and a controllable active area, based on polarization holography of tensor theory. First, we design two polarization holograms that reconstruct waves with only p- or s-polarization components, respectively. Then, after we recorded these two holograms on the same position of the recording material using the interference approach, as a result, a polarization splitter could readily be prepared. The separation angles of fabricated polarization splitters can be easily adjusted by changing the interference angle, and the active area can also be easily modified by changing the sizes of the interference beams and recording material during the recording process. The experimental results verify the reliability and accuracy of this method. We believe that this work may broaden the application field of polarization holography.

Generation of vector beams based on diffraction characteristics of a linear polarization hologram in coaxial recording.

Polarization holography is an effective tool for realizing light field manipulation and can be utilized to generate vector beams. Based on the diffraction characteristics of a linear polarization hologram in coaxial recording, an approach for generating arbitrary vector beams is proposed. Unlike the previous methods for generating vector beams, in this work, it is independent of faithful reconstruction effect and the arbitrary linear polarization waves can be used as reading waves. The desired generalized vector beam polarization patterns can be adjusted by changing the polarized direction angle of the reading wave. Therefore, it is more flexible than the previously reported methods in generating vector beams. The experimental results are consistent with the theoretical prediction.

Enhanced Polarization Properties of Holographic Storage Materials Based on RGO Size Effect.

Polarized holographic properties play an important role in the holographic data storage of traditional organic recording materials. In this study, reduced graphene oxide (RGO) was introduced into a phenanthraquinone-doped polymethylmethacrylate (PQ/PMMA) photopolymer to effectively improve the orthogonal polarization holographic properties of the material. Importantly, the lateral size of RGO nanosheets has an important influence on the polymerization of MMA monomers. To some extent, a larger RGO diameter is more conducive to promoting the polymerization of MMA monomers and can induce more PMMA polymers to be grafted on its surface, thus obtaining a higher PMMA molecular weight. However, too large of a RGO will lead to too much grafting of the PMMA chain to shorten the length of a single PMMA chain, which will lead to the degradation of PQ/PMMA holographic performance. Compared with the original PQ/PMMA, the diffraction efficiency of the RGO-doped PQ/PMMA photopolymer can reach more than 11.4% (more than 3.5 times higher than the original PQ/PMMA), and its photosensitivity is significantly improved by 4.6 times. This study successfully synthesized RGO-doped PQ/PMMA high-performance photopolymer functional materials for multi-dimensional holographic storage by introducing RGO nanoparticles. Furthermore, the polarization holographic properties of PQ/PMMA photopolymer materials can be further accurately improved to a new level.

Severe gut mucosal injury induces profound systemic inflammation and spleen-associated lymphoid organ response.

Clinical evidence indicates a connection between gut injuries, infections, inflammation, and an increased susceptibility to systemic inflammation. Nevertheless, the animal models designed to replicate this progression are inadequate, and the fundamental mechanisms are still largely unknown. This research explores the relationship between gut injuries and systemic inflammation using a Dextran Sulfate Sodium (DSS)-induced colonic mucosal injury mouse model. Continuous treatment of adult mice with 4% DSS drinking water yielded a remarkable mortality rate by day 7, alongside intensified gut injury and detectable peripheral inflammation. Moreover, RNAscope in situ hybridization with 16S rRNA probe noted bacterial penetration into deeper colon compartments of the mice following treatment with DSS for 7 days. Histological analysis revealed inflammation in the liver and lung tissues of DSS-treated mice. In addition, we found that DSS-treated mice exhibited elevation of Alanine transaminase (ALT) and Aspartate transaminase (AST) in peripheral blood and pro-inflammatory cytokine levels in the liver. Notably, the DSS-treated mice displayed a dampened metabolic profile, reduced CD45 marker expression, and an increase in apoptosis within the lymphoid organ such as spleen. These findings suggest that high-dose DSS-induced gut injury gives rise to sepsis-like systemic inflammation characterized by multiple organ injury and profound splenocyte apoptosis and dysfunction of CD45+ cells in the spleen, indicating the role of the spleen in the pathogenesis of gut-derived systemic inflammation. Together, the severe colonic mucosal injury model facilitates research into gut damage and associated peripheral immune responses, providing a vital framework for investigating mechanisms related to clinically relevant, gut-derived systemic inflammation.

Simultaneously characterized Stokes parameters of a lightwave utilizing the tensor polarization holography theory.

Polarization is a natural property of a lightwave and makes a significant contribution to various scientific and technological applications, due to the different states of polarization (SoP) of a lightwave that may manifest distinct behaviors. Hence, it is important to determine the SoP of the lightwave. Generally, the SoP of a lightwave can be recognized by the Stokes parameters. In this paper, we proposed a novel method to simultaneously characterize the Stokes parameters of a lightwave, by employing the tensor polarization holography theory. This is done through merely a piece of polarization-sensitive material. Compared with the traditional method, this method requires only one measurement to obtain all the Stokes parameters, without using additional polarizing elements. The experimental result shows excellent agreement with the theoretical one, which confirmed the reliability and accuracy of the proposed method. We believe that this work may broaden the application field of polarization holography.

Decision-free downsampling method assisted via channel-transfer information to improve the reliability of holographic data storage systems.

A decision-free downsampling method (DFDS) assisted by channel-transfer information for phase-modulated holographic data storage is proposed. DFDS is used to address the issue of the accumulation of decision errors induced by traditional downsampling. The issue degrades the downsampling accuracy. DFDS comprises two functional segments: acquiring the channel-transfer information offline and performing decision-free downsampling online. With the assistance of the channel-transfer information, DFDS uses Bayesian posterior probabilities instead of traditional decision results to avoid the accumulation of decision errors and achieve more accurate downsampling. The simulation and experimental results show that DFDS reduces the phase error rate, thereby improving the reliability of the holographic data storage system.

Phenanthraquinone-Doped Polymethyl Methacrylate Photopolymer for Holographic Recording.

Phenanthraquinone-doped polymethyl methacrylate (PQ/PMMA) photopolymers are considered to be the most promising holographic storage media due to their unique properties, such as high stability, a simple preparation process, low price, and volumetric shrinkage. This paper reviews the development process of PQ/PMMA photopolymers from inception to the present, summarizes the process, and looks at the development potential of PQ/PMMA in practical applications.

Simple method for generating special beams using polarization holography.

Vector vortex beams are a kind of special beam that simultaneously carry spin and orbital angular momentum. The generation of vector vortex beams usually requires a complex and expensive optical system, which becomes a bottleneck hindering its further application. Thus, a compact, low-cost and efficient special beam generation system is demanded. In this paper, a method that can produce vector vortex beams distributed anywhere in the equator of hybrid-order Poincaré Spheres based on polarization holography is proposed. Via changing some parameters of the device, this method can also produce the scalar vortex beams distributed at any position of the basic Poincaré Sphere and the vector beams distributed at the equator of the higher-order Poincaré Spheres. The work shows that polarization holography has the potential ability to regulate the spin and orbital angular momentum simultaneously, opening a new window for future research and applications of angular momentum space orientation.

Phase-distribution-aware adaptive decision scheme to improve the reliability of holographic data storage.

Owing to their high storage density and long storage life, holographic data storage (HDS) technologies are viable options for mass cold data storage in the era of big data. Phase-modulated holographic data storage (PHDS) is a promising implementation of HDS. However, because of complex noise in the storage channel, many errors remain after phase demodulation. This study investigates the phase decision in the data-reading stage of PHDS. We propose a phase-distribution-aware adaptive (PDAA) decision scheme to address the inaccurate thresholds in traditional phase decision schemes. The PDAA decision scheme can determine more accurate decision thresholds based on the phase distribution characteristics of each reconstructed phase data page and adaptively match different decision thresholds to each phase data page. The experimental results show that when compared to the traditional decision scheme, the PDAA decision scheme can significantly reduce the phase error of data pages, improving the data reliability of holographic storage.

Highly sensitive photopolymer for holographic data storage.

The insufficient photosensitivity of conventional organic recording materials such as phenanthraquinone-doped poly(methyl methacrylate) (PQ/PMMA) significantly limits the recording speed in holographic data storage. Accelerating the formation of free radicals using the photosensitizer PQ during the photoreaction process and increasing the C = C double bond concentration of the matrix are effective methods for improving the photosensitivity. Using the above methods, we doped PQ/PMMA with the co-photoinitiator triethanolamine and co-monomer acrylamide to improve the photosensitivity of the material. Compared with the original PQ/PMMA material, the photosensitivity was increased by 10 times, and the diffraction efficiency was increased by 20%. The role of each doping component was studied by characterization and analysis. In addition, the introduction of the cross-linking agent N,N'-methylene-bisacrylamide, having high sensitivity, reduced the shrinkage of the material. We verified the application of the new material in a collinear system, and its high sensitivity showed its great potential for holographic data storage.

Improving the data reliability of phase modulated holographic storage using a reliable bit aware low-density parity-check code.

Phase modulated holographic storage offers superior storage capacity and a longer life span compared with other storage technologies. However, its application is limited by its high raw bit error rate. We aimed to introduce low-density parity-check (LDPC) codes for data protection in phase modulated holographic storage systems. However, traditional LDPC codes can not fully exploit data error characteristics, causing inaccurate initial log-likelihood ratio (LLR) information, which degrades decoding performance, thus limiting the improvement degree of data reliability in phase modulated holographic storage. Therefore, we propose a reliable bit aware LDPC optimization method (RaLDPC) that analyzes and employs phase demodulation characteristics to obtain reliable bits. More accurate initial LLR weights are assigned to these reliable bits. Hence, the optimized initial LLR can reflect the reliability of the demodulated data more accurately. Experimental results show that RaLDPC can reduce the bit error rate by an average of 38.89% compared with the traditional LDPC code, improving the data reliability of phase modulated holographic storage.