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Simple Summary: Tunchang pigs are known for their good performance on roughage tolerance, which may alleviate the conflict between humans and livestock for grain resources. This study observed that Tunchang pigs can adapt to a high-fiber diet containing 5% crude fiber. The adaptive alterations in intestinal microbiota and the regulation of genes collectively facilitated the digestion of high-fiber diets in the host. These findings provide insight into the roughage tolerance of Tunchang pigs, and contribute to further exploration of host–microbiota interactions. Although studies have revealed the significant impact of dietary fiber on growth performance and nutrient digestibility, the specific characteristics of the intestinal microbiota and gene regulation in pigs capable of digesting high-fiber diets remained unclear. To investigate the traits associated with roughage tolerance in the Chinese indigenous pig breed, we conducted comparative analysis of growth performance, apparent fiber digestibility, intestinal microbiota, SCFA concentrations and intestinal transcriptome in Tunchang pigs, feeding them diets with different wheat bran levels. The results indicated that the growth performance of Tunchang pigs was not significantly impacted, and the apparent total tract digestibility of crude fiber was significantly improved with increasing dietary fiber content. High-fiber diets altered the diversity of intestinal microbiota, and increased the relative abundance of Prevotella, CF231, as well as the concentrations of isobutyrate, valerate and isovalerate. The LDA analysis identified potential microbial biomarkers that could be associated with roughage tolerance, such as Prevotella stercorea, and Eubacterium biforme. In addition, appropriate high-fiber diets containing 4.34% crude fiber upregulated the mRNA expressions of PYY, AQP8, and SLC5A8, while downregulating the mRNA expressions of CKM and CNN1.This indicated that appropriate high-fiber diets may inhibit intestine motility and increase the absorption of water and SCFAs. [ABSTRACT FROM AUTHOR]

Red phosphorus (RP) is an emerging visible‐light‐responsive photocatalyst, yet the rapid charge recombination has limited photocatalytic hydrogen production activity. In this work, a Z‐scheme heterostructure with RP nanolayer coated on high‐index (116) faceted anatase TiO2 nanoparticles (TiO2@RP) is designed and fabricated via chemical vapor deposition. Compared with pristine TiO2 and RP, the optimized TiO2@RP Z‐scheme heterostructure exhibits a significantly boosted photocatalytic activity for pure water splitting, with hydrogen evolution rate reaching 12.9 µmol·h−1, under simulated solar light irradiation. The strong interfacial interaction and staggered band alignment between (116) faceted TiO2 and RP result in the formation of built‐in electric field, which can drive the directional charge migration from the conduction band (CB) of TiO2 to the valance band (VB) of RP under light irradiation, with photoelectrons and holes of high redox ability maintained at the CB of RP and the VB of TiO2, respectively. This well‐designed heterostructure greatly promotes photogenerated charge separation and migration via a direct Z‐scheme charge transfer pathway. [ABSTRACT FROM AUTHOR]

PurposeHow herpes simplex virus (HSV) is transported from the infected neuron cell body to the axon terminal is poorly understood. Several viral proteins are candidates for regulating the process, but the evidence is controversial. We compared the results of Us9 deletions in two HSV strains (F and NS) using a novel quantitative assay to test the hypothesis that the viral protein Us9 regulates the delivery of viral DNA to the distal axon of retinal ganglion cells in vivo. We also deleted a nine-amino acid motif in the Us9 protein of F strain (Us9-30) to define the role of this domain in DNA delivery.MethodsThe vitreous chambers of murine eyes were infected with equivalent amounts of F or NS strains of HSV. At 3, 4, or 5 days post infection (dpi), both optic tracts (OT) were dissected and viral genome was quantified by qPCR.ResultsAt 3 dpi, the F strain Us9- and Us9-30 mutants delivered less than 10% and 1%, respectively, of the viral DNA delivered after infection with the Us9R (control) strain. By 4 and 5 dpi, delivery of viral DNA had only partially recovered. Deletion of Us9 in NS-infected mice has a less obvious effect on delivery of new viral DNA to the distal OT. By 3 dpi the NS Us9-strain delivered 22% of the DNA that was delivered by the NS wt, and by 4 and 5 dpi the amount of Us9-viral DNA was 96% and 81%, respectively.ConclusionsA highly conserved acidic cluster within the Us9 protein plays a critical role for genome transport to the distal axon. The transport is less dependent on Us9 expression in the NS than in the F strain virus. This assay can be used to compare transport efficiency in other neurotropic viral strains.

UnlabelledThe transcription factor ZNF217 is a candidate oncogene in the amplicon on chromosome 20q13 that occurs in 20% to 30% of primary human breast cancers and that correlates with poor prognosis. We show that Znf217 overexpression drives aberrant differentiation and signaling events, promotes increased self-renewal capacity, mesenchymal marker expression, motility, and metastasis, and represses an adult tissue stem cell gene signature downregulated in cancers. By in silico screening, we identified candidate therapeutics that at low concentrations inhibit growth of cancer cells expressing high ZNF217. We show that the nucleoside analogue triciribine inhibits ZNF217-induced tumor growth and chemotherapy resistance and inhibits signaling events [e.g., phospho-AKT, phospho-mitogen-activated protein kinase (MAPK)] in vivo. Our data suggest that ZNF217 is a biomarker of poor prognosis and a therapeutic target in patients with breast cancer and that triciribine may be part of a personalized treatment strategy in patients overexpressing ZNF217. Because ZNF217 is amplified in numerous cancers, these results have implications for other cancers.SignificanceThis study finds that ZNF217 is a poor prognostic indicator and therapeutic target in patients with breast cancer and may be a strong biomarker of triciribine treatment efficacy in patients. Because previous clinical trials for triciribine did not include biomarkers of treatment efficacy, this study provides a rationale for revisiting triciribine in the clinical setting as a therapy for patients with breast cancer who overexpress ZNF217.

Research has been conducted on the specific cytosolic proteins. The experiments demonstrate that the representatives of the Phox homology domains selectively bind to specific phosphatidylinositol phosphates.

In a calcium-dependent interaction critical for blood coagulation, vitamin K-dependent blood coagulation proteins bind cell membranes containing phosphatidylserine via ?-carboxyglutamic acid-rich (Gla) domains. Gla domain-mediated protein-membrane interaction is required for generation of thrombin, the terminal enzyme in the coagulation cascade, on a physiologic time scale. We determined by X-ray crystallography and NMR spectroscopy the lysophosphatidylserine-binding site in the bovine prothrombin Gla domain. The serine head group binds Gla domain-bound calcium ions and Gla residues 17 and 21, fixed elements of the Gla domain fold, predicting the structural basis for phosphatidylserine specificity among Gla domains. Gla domains provide a unique mechanism for protein-phospholipid membrane interaction. Increasingly Gla domains are being identified in proteins unrelated to blood coagulation. Thus, this membrane-binding mechanism may be important in other physiologic processes. [ABSTRACT FROM AUTHOR]

Background: The glucose transporter 2 (GLUT2) is constitutively expressed in pancreatic beta cells and hepatocytes of mice. It is the most important receptor in glucose-stimulated insulin release and hepatic glucose transport. The Sema4D is a signalin receptor on cell membranes. The correlation between Sema4D and GLUT2 has not been reported previously. We investigated whether knockdown of Sema4D could exert a hypoglycemic effect based on the increased GLUT2 expression in Sema4D -/- mice hepatocytes. Methods: The glucose tolerance test and insulin tolerance test in sema4D -/- and sema4D +/+ mice were compared before and after streptozotocin (STZ) injection; the expression of GLUT2 content on the membrane surface of both groups was verified by Western blot. Then, the levels of insulin and C-peptide in the serum of the two groups of mice after STZ injection were measured by ELISA; the differentially expressed mRNAs in the liver of the two groups of mice were analyzed by transcriptomic analysis; then the differences in the expression of GLUT2, glycogen, insulin and glucagon in the two groups of mice were compared by tissue section staining. Finally, metabolomics analysis was performed to analyze the metabolites differentially expressed in the two groups of mice. Key findings: First, Sema4D -/- male mice exhibited significantly greater glucose tolerance than wild-type mice in a hyperglycemic environment. Secondly, Sema4D -/- mice had more retained GLUT2 in liver membranes after STZ injection according to an immunofluorescence assay. After STZ injection, Sema4D -/- male mice did not exhibit fasting hyperinsulinemia like wild-type mice. Finally, analysis of metabolomic and immunohistochemical data also revealed that Sema4D -/- mice produce hypoglycemic effects by enhancing the pentose phosphate pathway, but not glycogen synthesis. Conclusions: Thus, Sema4D may play an important role in the regulation of glucose homeostasis by affecting GLUT2 synthesis. [ABSTRACT FROM AUTHOR]

Nsp15, a uridine specific endoribonuclease conserved across coronaviruses, processes viral RNA to evade detection by host defense systems. Crystal structures of Nsp15 from different coronaviruses have shown a common hexameric assembly, yet how the enzyme recognizes and processes RNA remains poorly understood. Here we report a series of cryo-EM reconstructions of SARS-CoV-2 Nsp15, in both apo and UTP-bound states. The cryo-EM reconstructions, combined with biochemistry, mass spectrometry, and molecular dynamics, expose molecular details of how critical active site residues recognize uridine and facilitate catalysis of the phosphodiester bond. Mass spectrometry revealed the accumulation of cyclic phosphate cleavage products, while analysis of the apo and UTP-bound datasets revealed conformational dynamics not observed by crystal structures that are likely important to facilitate substrate recognition and regulate nuclease activity. Collectively, these findings advance understanding of how Nsp15 processes viral RNA and provide a structural framework for the development of new therapeutics. Nsp15 is a uridine specific endoribonuclease present in all coronaviruses. Here, the authors determine the cryo-EM structures of SARS-CoV-2 Nsp15 in the apo and UTP-bound states, which together with biochemical experiments, mass spectrometry and molecular dynamics simulations provide insights into the catalytic mechanism of Nsp15 and its conformational dynamics. [ABSTRACT FROM AUTHOR]

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The surveillance of health care-associated infection (HAI) is an essential element of the infection control program. While whole-genome sequencing (WGS) has widely been adopted for genomic surveillance, its data processing remains to be improved. Here, we propose a three-level data processing pipeline for the precision genomic surveillance of microorganisms without prior knowledge: species identification, multi-locus sequence typing (MLST), and sub-MLST clustering. The former two are closely connected to what have widely been used in current clinical microbiology laboratories, whereas the latter one provides significantly improved resolution and accuracy in genomic surveillance. Comparing to a broadly used reference-dependent alignment/mapping method and an annotation-dependent pan-/core-genome analysis, we implemented our reference- and annotation-independent, k-mer-based, simplified workflow to a collection of Acinetobacter and Enterococcus clinical isolates for tests. By taking both single nucleotide variants and genomic structural changes into account, the optimized k-mer-based pipeline demonstrated a global view of bacterial population structure in a rapid manner and discriminated the relatedness between bacterial isolates in more detail and precision. The newly developed WGS data processing pipeline would facilitate WGS application to the precision genomic surveillance of HAI. In addition, the results from such a WGS-based analysis would be useful for the precision laboratory diagnosis of infectious microorganisms. [ABSTRACT FROM AUTHOR]

Several carbon dots doping with diferent elements (Ca, Ag, Au) were fabricated and their catalytic properties had been investigated in this paper. It was found that the Ag-doped carbon dots (CDAg) had played a role of mimic enzyme on the reaction of HAuCl4-H2O2 and generated nanogold particles with surface enhanced Raman scattering (SERS) and resonance Rayleigh scattering (RRS) effects. The aptamer (Apt) can be adsorbed on the CDAg surface and cause the catalysis weakening. When the target Pb(II) was added, it would combine with the Apt to produce firm complexes Pb-Apt and desorb CDAg, which caused its catalytic effect restore. The formed nanogold had a strong RRS peak (at 375 nm) and a high SERS peak (at 1615 cm−1) in the presence of molecular probe (Victoria blue B, VBB). The dual-model signals of SERS and RRS increased linearly with Pb(II) concentration increase within the scope of 0.006–0.46 μmol/L and 0.01–0.46 μmol/L. And their detection limits respectively were 0.0032 μmol/L and 0.0048 μmol/L Pb(II). [ABSTRACT FROM AUTHOR]