MYCN Amplification Is Associated with Repressed Cellular Immunity in Neuroblastoma: An In Silico Immunological Analysis of TARGET Database

Purpose: RNA and DNA sequencing data are traditionally used to discern intrinsic cellular pathways in cancer pathogenesis, their utility for investigating the tumor microenvironment (TME) has not been fully explored. This study explores the use of sequencing data to investigate immunity within the TME. Experimental design: Here, we use immune cell fraction estimation analysis to determine the immune profiles in the microenvironment of neuroblastoma (NB) based on RNA-seq data in the TARGET database. The correlation between immune cell transcripts and prognosis in pediatric NB is also investigated. Results: In silico analysis revealed a strong inverse correlation between MYCNamplification and leukocyte infiltration. This finding was validated by immunohistochemistry analysis in tumor samples. Moreover, the abundance of CD4 T cells strongly associated with better patient survival regardless of MYCN gene amplification, while those of CD8 T cells, NK or B cells do not. Based on characteristic cytokine expression of CD4 subsets in tumors, the Th2 rather than Th1 levels were associated with better prognosis. Conclusion: We found that the in silico analysis of TARGET database reflected tumor immunity and was validated by the immunohistochemical tumor data. Our results reveal the association of MYCN amplification with repressed cellular immunity and the potential prognostic value of infiltrating CD4 T cell transcripts in pediatric NB. This analysis illustrates the potential role of MYCN in NB as a regulator of immune privilege and characterizes the power of in silico analysis for delineating cancer immunology and risk stratification

Effects of Lactic Acid Stress on the Solid-state Fermentation of Pichia kudriavzevii

Nongxiangxing Baijiu distiller’s grains are rich in lactic acid. Pichia kudriavzevii is the dominant yeast. The effects of lactic acid on the solid-state fermentation characteristics of Nongxiangxing Baijiu of the dominant yeast were explored under lactic acid stress of different concentrations. The growth and metabolism changes of Pichia kudriavzevii (PY1) were investigated from the aspects of carbon source consumption, growth factor utilization, high temperature tolerance and main metabolite production. Results showed that, the lactic acid stress had no significant effect on the colony and cell morphology of P. kudriavzevii, but had a certain inhibition on the growth of cell. This reversible inhibition could be weakened by amino acids and vitamins. When the culture temperature exceeds 44 ℃, the effect of lactic acid on the growth of the strain was gradually replaced by temperature. In metabolism, lactic acid could improve the utilization rate of glucose, galactose, maltose, fructose and sucrose, increase the production of ethanol and esters, and reduce the production of higher alcohols. In summary, the lactic acid could affect the flavor formation of Nongxiangxing Baijiu by affecting the growth and metabolism of yeast, and could be used as the fermentation regulation factor of Nongxiangxing Baijiu

Self-assembly of hydrofluorinated Janus graphene monolayer:a versatile route for designing novel Janus nanoscrolls

With remarkably interesting surface activities, two-dimensional Janus materials arouse intensive interests recently in many fields. We demonstrate by molecular dynamic simulations that hydrofluorinated Janus graphene (J-GN) can self-assemble into Janus nanoscroll (J-NS) at room temperature. The van der Waals (vdW) interaction and the coupling of C-H/π/C-F interaction and π/π interaction are proven to offer the continuous driving force of self-assembly of J-GN. The results show that J-GN can self-assemble into various J-NSs structures, including arcs, multi-wall J-NS and arm-chair-like J-NS by manipulating its original geometry (size and aspect ratio). Moreover, we also investigated self-assembly of hydrofluorinated J-GN and Fe nanowires (NWs), suggesting that Fe NW is a good alternative to activate J-GN to form J-NS. Differently, the strong vdW interaction between J-GN and Fe NW provides the main driving force of the self-assembly. Finally, we studied the hydrogen sorption over the formed J-NS with a considerable interlayer spacing, which reaches the US DOE target, indicating that J-NS is a promising candidate for hydrogen storage by controlling the temperature of system. Our theoretical results firstly provide a versatile route for designing novel J-NS from 2D Janus nanomaterials, which has a great potential application in the realm of hydrogen storage/separation

Ambient Temperature and Morbidity: A Review of Epidemiological Evidence

Objective: In this paper, we review the epidemiological evidence on the relationship between ambient temperature and morbidity. We assessed the methodological issues in previous studies and proposed future research directions

Probiotics improve symptoms of patients with COVID-19 through gut-lung axis: a systematic review and meta-analysis

BackgroundMulti system symptoms such as gastrointestinal tract and respiratory tract exist in coronavirus disease 2019 (COVID-19) patients. There is a lack of reliable evidence to prove that probiotics are effective in improving these symptoms. In this study, we aimed to evaluate the efficacy of probiotics in meta-analysis.MethodsWe systematically searched PubMed, Embase, Web of Science, and Cochrane Library up to February 15, 2023. Randomized controlled trials or high quality retrospective studies comparing the efficacy of probiotics as supplementation with non-probiotics in improving symptoms for patients with COVID-19 were included. This meta-analysis assessed endpoints using Review Manager 5.3.ResultTen citations comprising 1198 patients with COVID-19 were included. The results showed that probiotics could increase the number of people with overall symptom improvement (RR = 1.62, 95% CI [1.10, 2.38], P = 0.01) and shorten the duration (days) of overall symptoms (MD = −1.26, 95% CI [−2.36, −0.16], P = 0.02). For the duration (days) of specific symptoms, probiotics could improve diarrhea (MD = −2.12, 95% CI [−2.41, −1.83], P < 0.00001), cough (MD = −2.21, 95% CI [-4.56, 0.13], P = 0.06) and shortness of breath (MD = −1.37, 95% CI [-2.22, −0.53], P = 0.001). Probiotics had no obvious effect on fever, headache and weakness. For inflammation, probiotics could effectively reduce C-reactive Protein (CRP) serum level (mg/L) (MD = −4.03, 95% CI [−5.12, −2.93], P < 0.00001). Regarding hospital stay (days), probiotics group was shorter than non-probiotics group (MD = −0.98, 95% CI [−1.95, −0.01], P = 0.05).ConclusionTo some extent probiotics could improve the overall symptoms, inflammatory reaction and shorten hospital stay of patients with COVID-19. Probiotics may improve gastrointestinal symptoms (such as improving intestinal flora and reducing the duration of diarrhea) and further improve respiratory symptoms through the gut-lung axis.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=398309, identifier: CRD42023398309

Inactivation of Fam20B in Joint Cartilage Leads to Chondrosarcoma and Postnatal Ossification Defects

During endochondral ossification, chondrocytes embed themselves in a proteoglycan-rich matrix during the proliferation-maturation transition. Accumulating evidence shows that proteoglycans are essential components for chondrocyte proliferation and differentiation. When we conditionally inactivated FAM20B (Family with sequence similarity 20 member-B), which is a newly identified xylose kinase essential for glycosaminoglycan (GAG) formation on the protein core of proteoglycans, from the dental mesenchyme using Osr2-Cre, which is also strongly expressed in joint cartilage, we found chondrosarcoma in the knee joint and remarkable defects of postnatal ossification in the long bones. Mechanistic analysis revealed that the defects were associated with gain of function in multiple signaling pathways in the epiphyseal chondrocytes, such as those derived by WNT, BMP, and PTHrP/IHH molecules, suggesting that the FAM20B-catalyzed proteoglycans are critical mediators for a signaling balance in the regulatory network controlling chondrocyte differentiation and proliferation. In particular, we demonstrated that the WNT inhibitor was able to rescue part of the bone defects in Osr2-Cre;Fam20B(fl/fl) mice, indicating that FAM20B-catalyzed proteoglycans regulate postnatal endochondral ossification partially through the mediation of WNT signaling

Comparison of endometrial preparation protocols (natural cycle versus hormone replacement cycle) for frozen embryo transfer (COMPETE) : A study protocol for a randomised controlled trial

Funding Information: This study is supported by General Projects of Social Development (2022SF-565). BWM is supported by a NHMRC Investigator grant (GNT1176437). BWM reports consultancy for ObsEva. BMW has received research funding from Ferring and Merck. The other authors have none to declare. Acknowledgements: We thank all the physicians, scientists, and embryologists in our IVF clinic for their assistance with data collection as well the patients for participating in this studyPeer reviewedPublisher PD

Ascorbic Acid Facilitates Neural Regeneration After Sciatic Nerve Crush Injury

Ascorbic acid (AA) is an essential micronutrient that has been safely used in the clinic for many years. The present study indicates that AA has an unexpected function in facilitating nerve regeneration. Using a mouse model of sciatic nerve crush injury, we found that AA can significantly accelerate axonal regrowth in the early stage [3 days post-injury (dpi)], a finding that was revealed by immunostaining and Western blotting for antibodies against GAP-43 and SCG10. On day 28 post-injury, histomorphometric assessments demonstrated that AA treatment increased the density, size, and remyelination of regenerated axons in the injured nerve and alleviated myoatrophy in the gastrocnemius. Moreover, the results from various behavioral tests and electrophysiological assays revealed that nerve injury-derived functional defects in motor and sensory behavior as well as in nerve conduction were significantly attenuated by treatment with AA. The potential mechanisms of AA in nerve regeneration were further explored by investigating the effects of AA on three types of cells involved in this process [neurons, Schwann cells (SCs) and macrophages] through a series of experiments. Overall, the data illustrated that AA treatment in cultured dorsal root ganglionic neurons resulted in increased neurite growth and lower expression of RhoA, which is an important inhibitory factor in neural regeneration. In SCs, proliferation, phagocytosis, and neurotrophin expression were all enhanced by AA. Meanwhile, AA treatment also improved proliferation, migration, phagocytosis, and anti-inflammatory polarization in macrophages. In conclusion, this study demonstrated that treatment with AA can promote the morphological and functional recovery of injured peripheral nerves and that this effect is potentially due to AA’s bioeffects on neurons, SCs and macrophages, three of most important types of cells involved in nerve injury and regeneration