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Vitamin D receptor (VDR) executes most of the biological functions of vitamin D. Beyond this, VDR is a transcriptional factor regulating the expression levels of many target genes, such as genes for tight junction proteins claudin-2, -5, -12, and -15. In this review, we discuss the progress of research on VDR that influences intestinal barriers in health and disease. We searched PubMed and Google Scholar using key words vitamin D, VDR, tight junctions, cancer, inflammation, and infection. We summarize the literature and progress reports on VDR regulation of tight junction distribution, cellular functions, and mechanisms (directly or indirectly). We review the impacts of VDR on barriers in various diseases, e.g., colon cancer, infection, inflammatory bowel disease, and chronic inflammatory lung diseases. We also discuss the limits of current studies and future directions. Deeper understanding of the mechanisms by which the VDR signaling regulates intestinal barrier functions allow us to develop efficient and effective therapeutic strategies based on levels of tight junction proteins and vitamin D/VDR statuses for human diseases.

Collective measurements on identically prepared quantum systems can extract more information than local measurements, thereby enhancing information-processing efficiency. Although this nonclassical phenomenon has been known for two decades, it has remained a challenging task to demonstrate the advantage of collective measurements in experiments. Here, we introduce a general recipe for performing deterministic collective measurements on two identically prepared qubits based on quantum walks. Using photonic quantum walks, we realize experimentally an optimized collective measurement with fidelity 0.9946 without post selection. As an application, we achieve the highest tomographic efficiency in qubit state tomography to date. Our work offers an effective recipe for beating the precision limit of local measurements in quantum state tomography and metrology. In addition, our study opens an avenue for harvesting the power of collective measurements in quantum information-processing and for exploring the intriguing physics behind this power. Demonstrating the advantage of collective measurements in experiments remains a daunting task. Here the authors introduce a general recipe for performing deterministic collective measurements on two identically prepared qubits based on quantum walks.

ObjectiveThe SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics.DesignCOVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province.ResultsAmong enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m6A methylation and changed binding capacity with ACE2.ConclusionWe report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.

Emerging evidence has demonstrated that gut microbiome plays essential roles in the pathogenesis of human diseases in distal organs. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Treatment with the only drug approved by the US Food and Drug Administration for use in ALS, riluzole, extends a patient׳s life span by only a few months. Thus, there is an urgent need to develop novel interventions that for alleviate disease progression and improve quality of life in patients with ALS. Here we present evidence that intestinal dysfunction and dysbiosis may actively contribute to ALS pathophysiology. We used G93A transgenic mice as a model of human ALS. The G93A mice show abnormal intestinal microbiome and damaged tight junctions before ALS disease onset. The mice were given 2% butyrate, a natural bacterial product, in the drinking water. In mice fed with butyrate, intestinal microbial homeostasis was restored, gut integrity was improved, and life span was prolonged compared with those in control mice. At the cellular level, abnormal Paneth cells—specialized intestinal epithelial cells that regulate the host–bacterial interactions—were significantly decreased in the ALS mice treated with butyrate. In both ALS mice and intestinal epithelial cells cultured from humans, butyrate treatment was associated with decreased aggregation of the G93A superoxide dismutase 1 mutated protein. The findings from this study highlight the complex role of the gut microbiome and intestinal epithelium in the progression of ALS and present butyrate as a potential therapeutic reagent for restoring ALS-related dysbiosis.

The in vitro analysis of bacterial–epithelial interactions in the intestine has been hampered by a lack of suitable intestinal epithelium culture systems. Here, we report a new experimental model using an organoid culture system to study pathophysiology of bacterial–epithelial interactions post Salmonella infection. Using crypt‐derived mouse intestinal organoids, we were able to visualize the invasiveness of Salmonella and the morphologic changes of the organoids. Importantly, we reported bacteria‐induced disruption of epithelial tight junctions in the infected organoids. In addition, we showed the inflammatory responses through activation of the NF‐κB pathway in the organoids. Moreover, our western blot, PCR, and immunofluorescence data demonstrated that stem cell markers (Lgr5 and Bmi1) were significantly decreased by Salmonella infection (determined using GFP‐labeled Lgr5 organoids). For the first time, we created a model system that recapitulated a number of observations from in vivo studies of the Salmonella‐infected intestine, including bacterial invasion, altered tight junctions, inflammatory responses, and decreased stem cells. We have demonstrated that the Salmonella‐infected organoid culture system is a new experimental model suitable for studying host–bacterial interactions. e12147 Using stem cell‐derived intestinal organoids, we were able to visualize the invasiveness of Salmonella, morphologic changes of the organoids, and showed the inflammatory responses through activating the NF‐κB pathway in the organoids. Moreover, we show that stem cell markers (Lgr5 and Bmi1) were decreased by Salmonella infection. Taken together, the model system we have recreated recapitulates for the first time a number of observations from in vivo studies of Salmonella‐infected gut. Thus, Salmonella‐infected organoid culture system is a new experimental model suitable for studying host–bacterial interactions.

Emerging evidence has demonstrated that intestinal homeostasis and the microbiome play essential roles in neurological diseases, such as Parkinson's disease. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons and muscle atrophy. Currently, there is no effective treatment. Most patients die within 3–5 years due to respiratory paralysis. Although the death of motor neurons is a hallmark of ALS, other organs may also contribute to the disease progression. We examined the gut of an ALS mouse model, G93A, which expresses mutant superoxide dismutase (SOD1G93A), and discovered a damaged tight junction structure and increased permeability with a significant reduction in the expression levels of tight junction protein ZO‐1 and the adherens junction protein E‐cadherin. Furthermore, our data demonstrated increased numbers of abnormal Paneth cells in the intestine of G93A mice. Paneth cells are specialized intestinal epithelial cells that can sense microbes and secrete antimicrobial peptides, thus playing key roles in host innate immune responses and shaping the gut microbiome. A decreased level of the antimicrobial peptides defensin 5 alpha was indeed found in the ALS intestine. These changes were associated with a shifted profile of the intestinal microbiome, including reduced levels of Butyrivibrio Fibrisolvens, Escherichia coli, and Fermicus, in G93A mice. The relative abundance of bacteria was shifted in G93A mice compared to wild‐type mice. Principal coordinate analysis indicated a difference in fecal microbial communities between ALS and wild‐type mice. Taken together, our study suggests a potential novel role of the intestinal epithelium and microbiome in the progression of ALS. Emerging evidence has demonstrated that intestinal homeostasis and microbiome play essential roles in neurological diseases, such as Parkinson's disease. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons and muscle atrophy. Our data provide the first evidence about leaky intestine and impaired microbiome that may play a potential role in ALS disease progression.

The mutual synchronization of spin-torque oscillators (STOs) is critical for communication, energy harvesting and neuromorphic applications. Short range magnetic coupling-based synchronization has spatial restrictions (few µm), whereas the long-range electrical synchronization using vortex STOs has limited frequency responses in hundreds MHz (<500 MHz), restricting them for on-chip GHz-range applications. Here, we demonstrate electrical synchronization of four non-vortex uniformly-magnetized STOs using a single common current source in both parallel and series configurations at 2.4 GHz band, resolving the frequency-area quandary for designing STO based on-chip communication systems. Under injection locking, synchronized STOs demonstrate an excellent time-domain stability and substantially improved phase noise performance. By integrating the electrically connected eight STOs, we demonstrate the battery-free energy-harvesting system by utilizing the wireless radio-frequency energy to power electronic devices such as LEDs. Our results highlight the significance of electrical topology (series vs. parallel) while designing an on-chip STOs system. Spin torque oscillators (STOs) are attractive potential alternative for many high frequency applications, due to their small area and CMOS compatibility. Here, Sharma et al succeed in the electrical synchronization of four STOs, and use their setup to demonstrate wireless and battery-free energy harvesting using eight STOs.

Full quantum state tomography (FQST) plays a unique role in the estimation of the state of a quantum system without a priori knowledge or assumptions. Unfortunately, since FQST requires informationally (over)complete measurements, both the number of measurement bases and the computational complexity of data processing suffer an exponential growth with the size of the quantum system. A 14-qubit entangled state has already been experimentally prepared in an ion trap, and the data processing capability for FQST of a 14-qubit state seems to be far away from practical applications. In this paper, the computational capability of FQST is pushed forward to reconstruct a 14-qubit state with a run time of only 3.35 hours using the linear regression estimation (LRE) algorithm, even when informationally overcomplete Pauli measurements are employed. The computational complexity of the LRE algorithm is first reduced from ∼1019 to ∼1015 for a 14-qubit state, by dropping all the zero elements, and its computational efficiency is further sped up by fully exploiting the parallelism of the LRE algorithm with parallel Graphic Processing Unit (GPU) programming. Our result demonstrates the effectiveness of using parallel computation to speed up the postprocessing for FQST, and can play an important role in quantum information technologies with large quantum systems.

The microbiome modulates numerous aspects of human physiology and is a crucial factor in the development of various human diseases. Vitamin D deficiency and downregulation of the vitamin D receptor (VDR) are also associated with the pathogenesis of diseases such as inflammatory bowel disease, cancers, obesity, diabetes, and asthma. VDR is a nuclear receptor that regulates the expression of antimicrobial peptides and autophagy regulator ATG16L1. Vitamin D may promote a balanced intestinal microbiome and improve glucose homeostasis in diabetes. However, how VDR regulates microbiome is not well known. In the current study, we hypothesize that VDR status regulates the composition and functions of the intestinal bacterial community. Fecal and cecal stool samples were harvested from Vdr knockout (Vdr−/−) and wild-type mice for bacterial DNA and then sequenced with 454 pyrosequencing. The sequences were denoised and clustered into operational taxonomic units, then queried against the National Center for Biotechnology Information database. Metagenomics were analyzed, and the abundances of genes involved in metabolic pathways were compared by reference to the Kyoto Encyclopedia of Genes and Genomes and Clusters of Orthologous Groups databases. In the Vdr−/− mice, Lactobacillus was depleted in the fecal stool, whereas Clostridium and Bacteroides were enriched. Bacterial taxa along the Sphingobacteria-to-Sphingobacteriaceae lineage were enriched, but no genera reached statistical significance. In the cecal stool, Alistipes and Odoribacter were depleted, and Eggerthella was enriched. Notably, all of the taxa upstream of Eggerthella remained unchanged. A comparison of Vdr−/− and wild-type samples revealed 40 (26 enriched, 14 depleted) and 72 (41 enriched, 31 depleted) functional modules that were significantly altered in the cecal and fecal microbiomes, respectively (both, P < 0.05), due to the loss of Vdr. In addition to phylogenetic differences in gut microbiome with different intestinal origins, we identify several important pathways, such as nucleotide-binding oligomerization domain–like receptor, affected by Vdr status, including amino acid, carbohydrate, and fatty acid synthesis and metabolism, detoxification, infections, signal transduction, and cancer and other diseases. Our study fills knowledge gaps by having investigated the microbial profile affected by VDR. Insights from our findings can be exploited to develop novel strategies to treat or prevent various diseases by restoring VDR function and healthy microbe–host interactions.

Myocardial ischemia/reperfusion (I/R) injury is associated with the poor outcome and higher mortality after myocardial infarction. Recent studies have revealed that miR‐199a‐5p participates in the process of myocardial I/R injury, but the precise roles and molecular mechanisms of miR‐199a‐5p in myocardial I/R injury remain not well‐studied. Ferroptosis has been proposed to promote cardiomyocyte death, closely associated with myocardial I/R injury. Herein, the present study aimed to explore the function and mechanisms by which miR‐199a‐5p regulates whether miR‐199a‐5p contributes to ferroptosis‐induced cardiomyocyte death responding to oxygen–glucose deprivation/reoxygenation (OGD/R) injury, an in vitro model of myocardial I/R injury focusing on Akt/eNOS signaling pathway. The results found that ferroptosis‐induced cardiomyocyte death occurs and is accompanied by an increase in miR‐199a‐5p level in OGD/R‐treated H9c2 cells. MiR‐199a‐5p inhibitor ameliorated ferroptosis‐induced cardiomyocyte death as evidenced by the increased cell viability, the reduced reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) activity, malondialdehyde (MDA) and Fe2+ contents, and the up‐regulated glutathione (GSH)/glutathione disulphide (GSSG) ratio as well as glutathione peroxidase 4 (Gpx4) protein expression in H9c2 cells‐exposed to OGD/R, while miR‐199a‐5p mimic had the opposite effects. In addition, OGD/R led to the inhibition of Akt/eNOS signaling pathway, which was also blocked by miR‐199a‐5p inhibitor and aggravated by miR‐199a‐5p mimic. Furthermore, LY294002, an inhibitor of Akt/eNOS signaling pathway, abrogated miR‐199a‐5p inhibitor‐induced the reduction of ferroptosis‐induced cardiomyocyte death. In summary, our findings demonstrated that miR‐199a‐5p plays a central role in stimulating ferroptosis‐induced cardiomyocyte death during ischemic/hypoxic injury via inhibiting Akt/eNOS signaling pathway.