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Gut microbiome is integral to the pathogenesis of ulcerative colitis. A novel probiotic Lactobacillus intestinalis (L. intestinalis) exerts a protective effect against dextran sodium sulfate‐induced colitis in mice. Based on flow cytometry, colitis‐associated Th17 cells are the target of L. intestinalis, which is supported by the lack of protective effects of L. intestinalis in T cell‐null Rag1−/− mice or upon anti‐IL‐17‐A antibody‐treated mice. Although L. intestinalis exerts no direct effect on T cell differentiation, it decreases C/EBPA‐driven gut epithelial SAA1 and SAA2 production, which in turn impairs Th17 cell differentiation. Cometabolism of L. intestinalis ALDH and host ALDH1A2 contributed to elevated biosynthesis of retinoic acid (RA), which accounts for the anti‐colitis effect in RAR‐α ‐mediated way. In a cohort of ulcerative colitis patients, it is observed that fecal abundance of L. intestinalis is negatively associated with the C/EBPA‐SAA1/2‐Th17 axis. Finally, L. intestinalis has a synergistic effect with mesalazine in alleviating murine colitis. In conclusion, L. intestinalis and associated metabolites, RA, have potential therapeutic effects for suppressing colonic inflammation by modulating the crosstalk between intestinal epithelia and immunity. By improving retinoic acid synthesis, a novel probiotic L. intestinalis exerts a protective effect against colitis. Retinoic acid triggers epithelial gene alteration, including SAA1, SAA2, and C/EBPA, to downregulate RORγt+ Th17 cells. L. intestinalis and its associated metabolite, retinoic acid, have potential therapeutic effects for suppressing colonic inflammation.

Currently, the JTAG debugging is the most popular technology in the embedded ARM system. After providing a perfect JTAG debug method based on the GPIO pins of ARM chip, the paper analyzed the inner technology by which JTAG standard was accomplished. At last, the focus has been put on the analyses of the Boundary-Scan Chain working processes.

Aim： We have investigated the effects of lysophosphatidylcholine （LPC）, a product of lipid peroxidation, on Aβ1-42-induced SH-SY5Y cell apoptosis. Methods： The viability of cultured SH-SY5Y cells was measured using a CCK-8 kit. Apoptosis was determined by Chipased flow cytometric assay. The mRNA transcription of Bcl-2, Bax, and caspase-3 were detected by using reverse transcription and real-time quantitative PCR and the protein levels of Bax and caspase-3 were analyzed by Western blotting. The cytosolic calcium concentration of SH-SY5Y cells was tested by calcium influx assay. G2A expression in SH-SY5Y cells was silenced by small interfering RNA. Results： Long-term exposure of SH-SY5Y cells to LPC augmented the neurotoxicity of Aβ1-42, Furthermore, after LPC treatment, the Bax/Bcl-XL ratio and the expression levels, as well as the activity of caspase-3 were, elevated, whereas the expression level of TRAF1 was reduced. Because LPC was reported to be a specific ligand for the orphan G-protein coupled receptor, G2A, we investigated LPC-mediated changes in calcium levels in SH-SY5Y cells. Our results demonstrated that LPC can enhance the Aβ1-42-induced elevation of intracellular calcium. Interestingly, Aβ1-42 significantly increased the expression of G2A in SH-SY5Y cells, whereas knockdown of G2A using siRNA reduced the effects of LPC on Aβ1-42induced neurotoxicity. Conclusion： The effects of LPC on Aβ1-42-induced apoptosis may occur through the signal pathways of the orphan G-protein coupled receptor.

Aim： Lapatinib is a dual inhibitor of EGFR and human epidermal growth factor receptor 2 （HER2）, and used to treat advanced breast cancer. To overcome its poor water solubility, we constructed lapatinib-incorporated lipoprotein-like nanoparticles （LTNPs）, and evaluated the particle characteristics and possible anti-breast cancer mechanisms. Methods： LTNPs （lapatinib bound to albumin as a core, and egg yolk lecithin forming a lipid corona） were prepared. The particle characteristics were investigated using transmission electron microscopy （TEM） and atomic force microscopy （AFM）. The uptake and subcellular localization of LTNPs, as well as the effects of LTNPs on cell cycle were examined in BT-474 human breast cancer cells in vitro. Mice bearing BT-474 subcutaneous xenograft were intravenously injected with coumarin-6 loaded LTNPs （30 mg/kg） to study the targeting mechanisms in vivo. Results： The LTNPs particles were generally spherical but flexible under TEM and AFM, and approximately 62.1 nm in size with a zeta potential of 22.80 mV. In BT-474 cells, uptake of LTNPs was mediated by endosomes through energy-dependent endocytosis involving clathrin-dependent pinocytosis and macropinocytosis, and they could effectively escape from endosomes to the cytoplasm. Treatment of BT-474 cells with LTNPs （20 μg/mL） induced a significant cell arrest at G0/G1 phase compared with the same concentration of lapatinib suspension. In mice bearing BT-474 xenograft, intravenously injected LTNPs was found to target and accumulate in tumors, and colocalized with HER2 and SPRAC （secreted protein, acidic and rich in cysteine）. Conclusion： LTNPs can be taken up into breast cancer cells through specific pathways in vitro, and targeted to breast cancer xenograft in vivo via enhanced permeability and retention effect and SPARC.

Background： Polyphamlacy and potentially inappropriate medications （PIMs） are prominent prescribing issties in elderly patients. This study was to investigate the different prevalence of PIM use in elderly inpatients between 65-70 years of age and 80 years or older, who were discharged from Geriatric Depamnent in West China Hospital. Methods： A large-scale cohort of 1796 inpatients aged 65 years or over was recruited. Respectively. 618 patients were 65 79 years and 1178 patients were 80 years or older. Updated 2012 Beers Criteria by the Anaerican Geriatric Society was applied to assess the use of PIM among the investigated samples. Results： A review of the prescribed medications identified 686 patients aged 80 years or older constimed at least one PIM giving a rate of 58.2%. Conversely, 268 （43.4%） patients aged 65-79 years consumed at least one PIM （x^2=40.18, P 〈 0.001）. Patients aged 80 years or older had higher hospitalization expenses, length of stay, co-morbidities, medical prescription, and mortality than patients aged 65-79 years （all with P 〈 0.001 ）. Patients aged 80 years or older were prescribed with more benzodiazepines, drugs with strong anticholmergic properties, megestrol, antipsychotics, theophylline, and aspirin. In multiple regression analysis, PIM use was significantly associated with female gender, age, number of diagnostic disease, and number of prescribed medication. Conclusions： The finding from this study revealed that inpatients aged 80 years or older encountered more PIM use than those aged 65-79 years. Anticholinergic properties, megestrol. antipsychotics, theophylline, and aspirin are medications that often prescribed to inpatients aged 80 years or older. Doctors should carefully choose drugs for the elderly, especially the elderly aged 80 years or older.

The current outbreak of coronavirus disease-2019 (COVID-19) poses unprecedented challenges to global health 1 . The new coronavirus responsible for this outbreak—severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—shares high sequence identity to SARS-CoV and a bat coronavirus, RaTG13 2 . Although bats may be the reservoir host for a variety of coronaviruses 3 , 4 , it remains unknown whether SARS-CoV-2 has additional host species. Here we show that a coronavirus, which we name pangolin-CoV, isolated from a Malayan pangolin has 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S proteins, respectively. In particular, the receptor-binding domain of the S protein of pangolin-CoV is almost identical to that of SARS-CoV-2, with one difference in a noncritical amino acid. Our comparative genomic analysis suggests that SARS-CoV-2 may have originated in the recombination of a virus similar to pangolin-CoV with one similar to RaTG13. Pangolin-CoV was detected in 17 out of the 25 Malayan pangolins that we analysed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus from pangolins that is closely related to SARS-CoV-2 suggests that these animals have the potential to act as an intermediate host of SARS-CoV-2. This newly identified coronavirus from pangolins—the most-trafficked mammal in the illegal wildlife trade—could represent a future threat to public health if wildlife trade is not effectively controlled. A newly identified coronavirus found in Malayan pangolins shares considerable sequence identity with SARS-CoV-2, which suggests that the latter may have originated from a recombination event involving SARS-related coronaviruses from bats and pangolins.

Emerging SARS-CoV-2 variants of concern (VOCs) harboring multiple mutations in the spike protein raise concerns on effectiveness of current vaccines that rely on the ancestral spike protein. Here, we design a quadrivalent mosaic nanoparticle vaccine displaying spike proteins from the SARS-CoV-2 prototype and 3 different VOCs. The mosaic nanoparticle elicits equivalent or superior neutralizing antibodies against variant strains in mice and non-human primates with only small reduction in neutralization titers against the ancestral strain. Notably, it provides protection against infection with prototype and B.1.351 strains in mice. These results provide a proof of principle for the development of multivalent vaccines against pandemic and potential pre-emergent SARS-CoV-2 variants. Emerging SARS-CoV-2 variants with multiple mutations raise concerns on vaccine effectiveness. Here, Kang et al . report that a quadrivalent mosaic nanoparticle vaccine displaying spike proteins from the SARS-CoV-2 prototype and three different VOCs confer protection against SARS-CoV-2 variants in mice.

Inflammation-based prognostic scores such as the neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), Glasgow prognostic score (GPS), and modified GPS (mGPS) have been reported to have prognostic value in patients with many types of cancer, including esophageal squamous cell carcinoma (ESCC). However, the role of the C-reactive protein/Albumin (CRP/Alb) ratio in ESCC has not yet been evaluated. A total of 468 patients suffering from histologically proven ESCC were enrolled between January 2000 and July 2010. The GPS, mGPS, NLR, PLR and CRP/Alb ratios were tested together with established prognostic factors in univariate and multivariate Cox regression analyses of overall survival (OS). The optimal cutoff level for the CRP/Alb ratio was 0.50. The CRP/Alb ratio (continuous) had higher AUC values at 12 months (0.796), 24 months (0.805), and 36 months (0.815) than the NLR, GPS and mGPS. In univariate analysis, the 5-year OS rate for patients with a CRP/Alb ratio > 0.50 was 43.4%, while the rate for patients with a CRP/Alb ratio ≤ 0.50 was 17.7% (P < 0.0001). In multivariate analysis, patients with a CRP/Alb ratio > 0.50 had worse survival than patients with a CRP/Alb ratio ≤ 0.50 (HR: 2.44; 95% CI: 1.82-3.26; P < 0.0001). In summary, to the best of our knowledge, this is the first study to identify the CRP/Alb ratio as a novel inflammation-based prognostic factor in a large group of ESCC patients. The prognostic value of the CRP/Alb ratio needs to be verified in prospective multicenter studies.

Aims Grain yields of summer maize are significantly affected by different nitrogen (N) rates and depths through regulating root growth and distribution in soil. Understanding of effects of the deep placement of N on the root and shoot growth, grain yield and N use efficiency in summer maize are limited. Methods In this study, four N rates: 225, 191.25, 157.5 and 0 kg ha −1 applied at four depths: 5, 10, 15, and 20 cm were studied. Soil N content, root dry weight, root length density, biomass, grain yield and N use efficiency of maize were measured. Results Compared to 225 kg N ha −1 applied at a depth of 5 cm, a 15% reduction in the N application rate at a depth of 15 cm induced a larger root length density in the subsoil, as well as a larger rooting depth. It also facilitated maintaining a higher level of biomass and N accumulation during the later growth period, which increased the N assimilation of grain and enhanced grain yield by 3.9%, N recovery efficiency by 66.7%, N agronomic efficiency by 38.5%, and partial factor productivity of N by 22.1%. Conclusions Overall, this study demonstrates that reducing the recommended N application rate of 225 kg ha −1 by 15% but applying it at a depth of 15 cm might be considered an efficient fertilization method that increases agricultural productivity and N use efficiency.

In this paper, an inhomogeneous discrete nonlinear Schrödinger equation is analytically investigated. The modulation instability condition and conservation laws are derived. By virtue of the discrete Darboux transformation, two types of explicit solutions on the vanishing and non-vanishing backgrounds are generated. Those results might be useful in the study of solitons propagation in discrete optical fibers.