Development of a High-throughput Sequencing Platform for Detection of Viral Encephalitis Pathogens Based on Amplicon Sequencing.

Objective: Viral encephalitis is an infectious disease severely affecting human health. It is caused by a wide variety of viral pathogens, including herpes viruses, flaviviruses, enteroviruses, and other viruses. The laboratory diagnosis of viral encephalitis is a worldwide challenge. Recently, high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections. Thus, In this study, we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods: We designed nine pairs of specific polymerase chain reaction (PCR) primers for the 12 viruses by reviewing the relevant literature. The detection ability of the primers was verified by software simulation and the detection of known positive samples. Amplicon sequencing was used to validate the samples, and consistency was compared with Sanger sequencing. Results: The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×, and the sequence lengths were consistent with the sizes of the predicted amplicons. The sequences were verified using the National Center for Biotechnology Information BLAST, and all results were consistent with the results of Sanger sequencing. Conclusion: Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis. It is also a useful tool for the high-volume screening of clinical samples.

Investigation of the Microbiome of Industrial PDO Sfela Cheese and Its Artisanal Variants Using 16S rDNA Amplicon Sequencing and Shotgun Metagenomics.

Sfela is a white brined Greek cheese of protected designation of origin (PDO) produced in the Peloponnese region from ovine, caprine milk, or a mixture of the two. Despite the PDO status of Sfela, very few studies have addressed its properties, including its microbiology. For this reason, we decided to investigate the microbiome of two PDO industrial Sfela cheese samples along with two non-PDO variants, namely Sfela touloumotiri and Xerosfeli. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), 16S rDNA amplicon sequencing and shotgun metagenomics analysis were used to identify the microbiome of these traditional cheeses. Cultured-based analysis showed that the most frequent species that could be isolated from Sfela cheese were Enterococcus faecium, Lactiplantibacillus plantarum, Levilactobacillus brevis, Pediococcus pentosaceus and Streptococcus thermophilus. Shotgun analysis suggested that in industrial Sfela 1, Str. thermophilus dominated, while industrial Sfela 2 contained high levels of Lactococcus lactis. The two artisanal samples, Sfela touloumotiri and Xerosfeli, were dominated by Tetragenococcus halophilus and Str. thermophilus, respectively. Debaryomyces hansenii was the only yeast species with abundance > 1% present exclusively in the Sfela touloumotiri sample. Identifying additional yeast species in the shotgun data was challenging, possibly due to their low abundance. Sfela cheese appears to contain a rather complex microbial ecosystem and thus needs to be further studied and understood. This might be crucial for improving and standardizing both its production and safety measures.

Improving water quality and mitigating CH4 and N2O production in urban landscape water simultaneously by optimizing calcium peroxide dosage.

Recent studies show that greenhouse gas (GHG) emissions from urban landscape water are significant and cannot be overlooked, underscoring the need to develop effective strategies for mitigating GHG production from global freshwater systems. Calcium peroxide (CaO2) is commonly used as an eco-friendly reagent for controlling eutrophication in water bodies, but whether CaO2 can reduce GHG emissions remains unclear. This study investigated the effects of CaO2 dosage on the production of methane (CH4) and nitrous oxide (N2O) in urban landscape water under anoxic conditions during summer. The findings reveal that CaO2 addition not only improved the physicochemical and organoleptic properties of simulated urban landscape water but also reduced N2O production by inhibiting the activity of denitrifying bacteria across various dosages. Moreover, CaO2 exhibited selective effects on methanogens. Specifically, the abundance of acetoclastic methanogen Methanosaeta and methylotrophic methanogen Candidatus_Methanofastidiosum increased whereas the abundance of the hydrogenotrophic methanogen Methanoregula decreased at low, medium, and high dosages, leading to higher CH4 production at increased CaO2 dosage. A comprehensive multi-objective evaluation indicated that an optimal dosage of 60 g CaO2/m2 achieved 41.21 % and 84.40 % reductions in CH4 and N2O production, respectively, over a 50-day period compared to the control. This paper not only introduces a novel approach for controlling the production of GHGs, such as CH4 and N2O, from urban landscape water but also suggests a methodology for optimizing CaO2 dosage, providing valuable insights for its practical application.

A hybrid topological quantum state in an elemental solid.

Topology1-3 and interactions are foundational concepts in the modern understanding of quantum matter. Their nexus yields three important research directions: (1) the competition between distinct interactions, as in several intertwined phases, (2) the interplay between interactions and topology that drives the phenomena in twisted layered materials and topological magnets, and (3) the coalescence of several topological orders to generate distinct novel phases. The first two examples have grown into major areas of research, although the last example remains mostly unexplored, mainly because of the lack of a material platform for experimental studies. Here, using tunnelling microscopy, photoemission spectroscopy and a theoretical analysis, we unveil a 'hybrid' topological phase of matter in the simple elemental-solid arsenic. Through a unique bulk-surface-edge correspondence, we uncover that arsenic features a conjoined strong and higher-order topology that stabilizes a hybrid topological phase. Although momentum-space spectroscopy measurements show signs of topological surface states, real-space microscopy measurements unravel a unique geometry of topologically induced step-edge conduction channels revealed on various natural nanostructures on the surface. Using theoretical models, we show that the existence of gapless step-edge states in arsenic relies on the simultaneous presence of both a non-trivial strong Z2 invariant and a non-trivial higher-order topological invariant, which provide experimental evidence for hybrid topology. Our study highlights pathways for exploring the interplay of different band topologies and harnessing the associated topological conduction channels in engineered quantum or nano-devices.

Manipulating chiral spin transport with ferroelectric polarization.

A magnon is a collective excitation of the spin structure in a magnetic insulator and can transmit spin angular momentum with negligible dissipation. This quantum of a spin wave has always been manipulated through magnetic dipoles (that is, by breaking time-reversal symmetry). Here we report the experimental observation of chiral spin transport in multiferroic BiFeO3 and its control by reversing the ferroelectric polarization (that is, by breaking spatial inversion symmetry). The ferroelectrically controlled magnons show up to 18% modulation at room temperature. The spin torque that the magnons in BiFeO3 carry can be used to efficiently switch the magnetization of adjacent magnets, with a spin-torque efficiency comparable to the spin Hall effect in heavy metals. Utilizing such controllable magnon generation and transmission in BiFeO3, an all-oxide, energy-scalable logic is demonstrated composed of spin-orbit injection, detection and magnetoelectric control. Our observations open a new chapter of multiferroic magnons and pave another path towards low-dissipation nanoelectronics.

Exploration of Molecular Nanoparticles as Soft Structural Materials and Their Structure-Property Relationship.

The search for alternative chemical systems other than polymers with chain topologies for soft structural materials raises general interests in fundamental materials and chemical sciences. It is also appealing from an engineering perspective for the urgent need to resolve the typical trade-offs of polymer systems. Herein, a subnanometer molecular cluster, polyhedral oligomeric silsesquioxanes, is assembled into molecular nanoparticles (MNPs) with star topology. Broadly tunable viscoelasticity can be realized by fine-tuning the MNPs' deformability. Being analogous to polymeric systems, the hierarchical structural relaxation dynamics can be observed, and their relaxation time and temperature dependence are dominated by the linker flexibilities. This not only provides microscopic understanding on MNP's unique viscoelasticity but also offers enormous opportunities for modulating their mechanical properties via linker engineering. Our work proves the possibility of applying structural units with particle topologies for the design of soft structural materials.

Unique Viscoelasticity and Hierarchical Relaxation Dynamics of Molecular Granular Materials.

Resulting from the dense packing of subnanometer molecular clusters, molecular granular materials (MGMs) are shown to maintain high elasticity far above their apparent glass transition temperature (Tg*). However, our microscopic understanding of their structure-property relationship is still poor. Herein, 1 nm polyhedral oligomeric silsesquioxanes (POSSs) are appended to a backbone chain in a brush configuration with different flexible linker chains. Assemblies of these brush polymers exhibit hierarchical relaxation dynamics with the glass transition arising from the cooperative dynamics of packed POSSs. The interaction among the assemblies can be strengthened by increasing the rigidity of linkers with the MGM relaxation modes changing from colloid- to polymer chain-like behavior, rendering their tunable viscoelasticity. This finally contributes to the decoupling of mechanical and thermal properties by showing elasticity dominant mechanical properties at a temperature 150 K above the Tg*.

Role of Angiopoietin/Tie2 System in Sepsis: A Potential Therapeutic Target.

Sepsis is a disorder of host response caused by severe infection that can lead to life-threatening organ dysfunction. There is no specific treatment for sepsis. Although there are many different pathogens that can cause sepsis, endothelial dysfunction is a frequent mechanism resulting in vascular leakage and coagulation problem. Recent studies on the regulatory pathways of vascular endothelium have shown that the disturbance of angiopoietin (Ang) /Tie2 axis can induce endothelial cell activation, which is the core pathogenesis of sepsis. In this review, we aim to discuss the regulation of Ang/Tie2 axis and the biomarkers involved in the context of sepsis. Also, we attempt to explore the prospective and feasibility of Ang/Tie2 axis as a potential target for sepsis intervention to improve clinical outcomes.

Neurotoxicities induced by micro/nanoplastics: A review focusing on the risks of neurological diseases.

Pollution of micro/nano-plastics (MPs/NPs) is ubiquitously prevalent in the environment, leading to an unavoidable exposure of the human body. Despite the protection of the blood-brain barrier, MPs/NPs can be transferred and accumulated in the brain, which subsequently exert negative effects on the brain. Nevertheless, the potential neurodevelopmental and/or neurodegenerative risks of MPs/NPs remain largely unexplored. In this review, we provide a systematic overview of recent studies related to the neurotoxicity of MPs/NPs. It covers the environmental hazards and human exposure pathways, translocation and distribution into the brain, the neurotoxic effects, and the possible mechanisms of environmental MPs/NPs. MPs/NPs are widely found in different environment matrices, including air, water, soil, and human food. Ambient MPs/NPs can enter the human body by ingestion, inhalation and dermal contact, then be transferred into the brain via the blood circulation and nerve pathways. When MPs/NPs are present in the brain, they can initiate a series of molecular or cellular reactions that may harm the blood-brain barrier, cause oxidative stress, trigger inflammatory responses, affect acetylcholinesterase activity, lead to mitochondrial dysfunction, and impair autophagy. This can result in abnormal protein folding, loss of neurons, disruptions in neurotransmitters, and unusual behaviours, ultimately contributing to the initiation and progression of neurodegenerative changes and neurodevelopmental abnormalities. Key challenges and further research directions are also proposed in this review as more studies are needed to focus on the potential neurotoxicity of MPs/NPs under realistic conditions.

Topical application of calcitonin gene-related peptide as a regenerative, antifibrotic, and immunomodulatory therapy for corneal injury.

Calcitonin gene-related peptide (CGRP) is a multifunctional neuropeptide abundantly expressed by corneal nerves. Using a murine model of corneal mechanical injury, we found CGRP levels in the cornea significantly reduced after injury. Topical application of CGRP as an eye drop accelerates corneal epithelial wound closure, reduces corneal opacification, and prevents corneal edema after injury in vivo. CGRP promotes corneal epithelial cell migration, proliferation, and the secretion of laminin. It reduces TGF-ß1 signaling and prevents TGF-ß1-mediated stromal fibroblast activation and tissue fibrosis. CGRP preserves corneal endothelial cell density, morphology, and pump function, thus reducing corneal edema. Lastly, CGRP reduces neutrophil infiltration, macrophage maturation, and the production of inflammatory cytokines in the cornea. Taken together, our results show that corneal nerve-derived CGRP plays a cytoprotective, pro-regenerative, anti-fibrotic, and anti-inflammatory role in corneal wound healing. In addition, our results highlight the critical role of sensory nerves in ocular surface homeostasis and injury repair.

Modulation of chronic obstructive pulmonary disease progression by antioxidant metabolites from Pediococcus pentosaceus: enhancing gut probiotics abundance and the tryptophan-melatonin pathway.

Chronic obstructive pulmonary disease (COPD), a condition primarily linked to oxidative stress, poses significant health burdens worldwide. Recent evidence has shed light on the association between the dysbiosis of gut microbiota and COPD, and their metabolites have emerged as potential modulators of disease progression through the intricate gut-lung axis. Here, we demonstrate the efficacy of oral administration of the probiotic Pediococcus pentosaceus SMM914 (SMM914) in delaying the progression of COPD by attenuating pulmonary oxidative stress. Specially, SMM914 induces a notable shift in the gut microbiota toward a community structure characterized by an augmented abundance of probiotics producing short-chain fatty acids and antioxidant metabolisms. Concurrently, SMM914 synthesizes L-tryptophanamide, 5-hydroxy-L-tryptophan, and 3-sulfino-L-alanine, thereby enhancing the tryptophan-melatonin pathway and elevating 6-hydroxymelatonin and hypotaurine in the lung environment. This modulation amplifies the secretion of endogenous anti-inflammatory factors, diminishes macrophage polarization toward the M1 phenotype, and ultimately mitigates the oxidative stress in mice with COPD. The demonstrated efficacy of the probiotic intervention, specifically with SMM914, not only highlights the modulation of intestine microbiota but also emphasizes the consequential impact on the intricate interplay between the gastrointestinal system and respiratory health.

Astragalus membranaceus Polysaccharide Regulates Small Intestinal Microbes and Activates IL-22 Signal Pathway to Promote Intestinal Stem Cell Regeneration in Aging Mice.

Aging can cause degenerative changes in multiple tissues and organs. Gastrointestinal diseases and dysfunctions are common in the elderly population. In this study, we investigated the effects of Astragalus membranaceus polysaccharide (APS) and Astragalus membranaceus ethanol extract (AEE) on age-related intestinal dysfunction and gut microbiota dysbiosis in naturally aging mice. The energy expenditure and physical activity of 23-month-old C57BL6/J mice were recorded using a metabolic cage system. Pathological changes in the intestine were evaluated using Alcian blue staining. The protein levels of leucine-rich repeats containing G protein-coupled receptor 5 (Lgr5) and Stat3 in the small intestine were determined using immunohistochemistry. The intestinal cell migration distance was assessed using bromodeoxyuridine (BrdU) immunofluorescence staining. The gene transcription levels of intestinal stem cell (ISC) markers and ISC-related signaling pathways were detected using quantitative real-time PCR (qRT-PCR). Microbiota analysis based on 16S rDNA was performed to evaluate the composition of the gut microbiota. APS and AEE improved a series of aging phenotypes in female but not in male aging mice. APS and AEE ameliorate intestinal dysfunction and histopathological changes in aging mice. APS had a more significant anti-aging effect than AEE, particularly on intestinal dysfunction. APS promotes ISC regeneration by activating the IL-22 signaling pathway. Cohousing (CH) experiments further confirmed that APS induced the IL-22 signaling pathway by increasing the abundance of Lactobacillus, thereby promoting the regeneration of ISCs. Our results show that APS may serve as a promising agent for improving age-related intestinal dysfunction.

Construction of porous flower-like Ru-doped CoNiFe layered double hydroxide for supercapacitors and oxygen evolution reaction catalysts.

In recent years, ternary layered double hydroxide (LDH) has become a research hotspot for electrode materials and oxygen evolution reaction (OER) catalyst due to the enhanced synergistic effect between individual elements. However, the application of LDH is greatly limited by its low electrical conductivity and the disadvantage that nanosheets tend to accumulate and mask the active sites. Herein, a novel Ru-doped CoNiFe - LDH was prepared via a facile hydrothermal method. According to the density functional theory (DFT) calculations, the doping of Ru element could improve electron state density and band gaps of LDH and consequently boosted the electrochemical reaction kinetics as well as electrical conductivity. Furthermore, introduction of Ru atom induced the formation of porous flower-like structures in nanosheets. Compared to CoNiFe - LDH (28.9 m2/g), Ru-doped CoNiFe - LDH performed larger specific surface area of 53.1 m2/g, resulting in more electrochemically active sites. In these case, Ru-doped CoNiFe - LDH demonstrated better energy storage performance of 176.0 mAh/g at 1 A/g compared to original CoNiFe - LDH (78.9 mAh/g at 1 A/g). Besides, the assembled Ru-doped CoNiFe - LDH//activated carbon (AC) device delivered a maximum energy density of 36.4 W h kg-1 at the power density of 740.3 W kg-1 and an outstanding cycle life (78.7 % after 10,000 cycles). Meanwhile, Ru-doped CoNiFe - LDH exhibited lower overpotential (339 mV at 50 mA cm-2) and Tafel slope (93.2 mV dec-1). Therefore, this work provided novel and valuable insights into the rational doping of Ru elements for the controlled synthesis of supercapacitor electrode materials and OER catalysts.

Eosinophilic gastritis and gluten-sensitive enteropathy manifested as hypoproteinemia and treated with omalizumab: a case report.

BACKGROUND: Eosinophilic gastritis (EoG) has rarely been reported in conjunction with gluten-sensitive enteropathy (GSE). When this does occur, patients typically present with gastrointestinal symptoms. To our knowledge, hypoproteinemia has not been reported as the primary manifestation. Anti-IgE therapy, such as omalizumab, lowers eosinophil counts in the blood, lungs, and gut. Its efficiency in treating active EoG remain unknown. CASE PRESENTATION: We report a 33-month-old boy with a history of food allergy and atopic dermatitis who developed recurrent edema, hypoproteinemia, and eosinophilia at the age of 14 months. The diagnoses of EoG and GSE were confirmed based on the clinical presentation and results of gastrointestinal biopsies and serological testing. Although prednisone and dietary intervention were initially effective, the boy developed prednisone-related facial swelling. After stopping prednisone, his symptoms relapsed. Subsequent treatment with omalizumab, combined with dietary intervention, showed good efficacy and safety. CONCLUSIONS: To our knowledge, this is the first case of concurrent EoG and GSE that presented primarily with hypoproteinemia. We highlight the rare manifestations of these two diseases to raise clinical suspicion and prevent missed and delayed diagnoses. The pathogenesis of EoG is heterogeneous and complex. Omalizumab showed good efficacy, indicating that IgE-mediated processes may be involved in the pathogenesis of this patient's diseases.

Recombinant Human Collagen Type III Improves Hypertrophic Scarring by Regulating the Ratio of Type I/III Collagen.

Hypertrophic scar development is a complication associated with wound healing, impacting local appearance and function. The type I/III collagen ratio affects the extent of hypertrophic scarring; a reduced ratio can ameliorate this. In this study, recombinant human collagen type III was developed. Liquid chromatography-tandem mass spectrometry was used to determine its amino acid sequence and confirm its high level of homology with natural human type III collagen. Recombinant human collagen type III displayed no cytotoxicity and did not confer skin irritation and sensitization. Immunofluorescence and western blot analyses of histidine following incubation with fibroblasts suggested cell entry of recombinant human collagen type III. Furthermore, recombinant human collagen type III promoted the synthesis of the natural type III collagen in fibroblasts, resulting in a more obvious increase of type III collagen content in fibroblasts than that of type I collagen, and then decreased the ratio of type I/III collagen. The results of 5-ethynyl-2'-deoxyuridine staining assay suggested enhanced fibroblast proliferation. Following local injection of recombinant human collagen type III, rabbit ear scarring was significantly reduced after 60 days. Vancouver Scar Scale evaluation showed that all index scores were significantly reduced. Western blotting and Picro-Sirius red staining showed that the natural type III collagen increase in scar tissue was greater than that of type I collagen, decreasing the type I/III ratio. In summary, recombinant human collagen type III can be taken up by fibroblasts and promote natural collagen synthesis-especially that of type III-thereby reducing the type I/III ratio and improving hypertrophic scarring.

Therapeutic Effects of Stimulating the Melanocortin Pathway in Regulating Ocular Inflammation and Cell Death.

Alpha-melanocyte-stimulating hormone (α-MSH) and its binding receptors (the melanocortin receptors) play important roles in maintaining ocular tissue integrity and immune homeostasis. Particularly extensive studies have demonstrated the biological functions of α-MSH in both immunoregulation and cyto-protection. This review summarizes the current knowledge of both the physiological and pathological roles of α-MSH and its receptors in the eye. We focus on recent developments in the biology of α-MSH and the relevant clinical implications in treating ocular diseases.

Exposure to MEHP during Pregnancy and Lactation Impairs Offspring Growth and Development by Disrupting Thyroid Hormone Homeostasis.

Mono(2-ethylhexyl) phthalate (MEHP), as a highly toxic and biologically active phthalate metabolite, poses considerable risks to the environment and humans. Despite the existence of in vitro studies, there is a lack of in vivo experiments assessing its toxicity, particularly thyroid toxicity. Herein, we investigated the thyroid-disrupting effects of MEHP and the effects on growth and development of maternal exposure to MEHP during pregnancy and lactation on the offspring modeled by SD rats. We found that thyroid hormone (TH) homeostasis was disrupted in the offspring, showing a decrease in total TH levels, combined with an increase in free TH levels. Nonhomeostasis ultimately leads to weight loss in female offspring, longer anogenital distance in male offspring, prolonged eye-opening times, and fewer offspring. Our findings indicate that maternal exposure to MEHP during pregnancy and lactation indirectly influences the synthesis, transport, transformation, and metabolism of THs in the offspring. Meanwhile, MEHP disrupted the morphology and ultrastructure of the thyroid gland, leading to TH disruption. This hormonal disruption might ultimately affect the growth and development of the offspring. This study provides a novel perspective on the thyroid toxicity mechanisms of phthalate metabolites, emphasizing the health risks to newborns indirectly exposed to phthalates and their metabolites.