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H1s, or linker histones, are ubiquitous proteins in eukaryotic cells, consisting of a globular GH1 domain flanked by two unstructured tails. Whilst it is known that numerous non-allelic variants exist within the same species, the degree of interspecific and intraspecific variation and divergence of linker histones remain unknown. The conserved basic binding sites in GH1 and evenly distributed strong positive charges on the C-terminal domain (CTD) are key structural characters for linker histones to bind chromatin. Based on these features, we identified five linker histones from 13 GH1-containing proteins in castor bean ( Ricinus communis ), which were named as RcH1.1, RcH1.2a, RcH1.2b, RcH1.3, and RcH1.4 based on their phylogenetic relationships with the H1s from five other economically important Euphorbiaceae species ( Hevea brasiliensis Jatropha curcas , Manihot esculenta Mercurialis annua , and Vernicia fordii ) and Arabidopsis thaliana . The expression profiles of RcH1 genes in a variety of tissues and stresses were determined from RNA-seq data. We found three RcH1 genes ( RcH1.1 , RcH1.2a , and RcH1.3 ) were broadly expressed in all tissues, suggesting a conserved role in stabilizing and organizing the nuclear DNA. RcH1.2a and RcH1.4 was preferentially expressed in floral tissues, indicating potential involvement in floral development in castor bean. Lack of non-coding region and no expression detected in any tissue tested suggest that RcH1.2b is a pseudogene. RcH1.3 was salt stress inducible, but not induced by cold, heat and drought in our investigation. Structural comparison confirmed that GH1 domain was highly evolutionarily conserved and revealed that N- and C-terminal domains of linker histones are divergent between variants, but highly conserved between species for a given variant. Although the number of H1 genes varies between species, the number of H1 variants is relatively conserved in more closely related species (such as within the same family). Through comparison of nucleotide diversity of linker histone genes and oil-related genes, we found similar mutation rate of these two groups of genes. Using Tajima's D and ML-HKA tests, we found RcH1.1 and RcH1.3 may be under balancing selection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guo, Li, Yu, Chapman and Liu.)

Introduction: Patients with diabetes mellitus and end-stage renal disease are at a high risk of developing coronary, cerebrovascular, and peripheral vascular diseases. This study aimed to characterize hypoglycemia and blood glucose fluctuations associated with maintenance hemodialysis in older adult patients with diabetes mellitus and end-stage renal disease using a continuous glucose monitoring system., Methods: Seven patients were enrolled in this study, and 13 pairs of continuous glucose monitoring system data were collected. Each pair included data of 1 dialysis-on day and 1 dialysis-off day. Information on basic patient characteristics, including age, diabetes mellitus duration, hemodialysis duration, and proportions of hemoglobin A1c and glycated albumin, were collected. Differences in blood glucose fluctuation were compared between dialysis-on days and dialysis-off days., Results: The mean blood glucose on dialysis-on days (6.96 ± 2.57 mmol/L) was significantly lower than that on dialysis-off days (7.68 ± 2.31 mmol/L; P < 0.05). In contrast, the following parameters had significantly higher values (all P < 0.05) on dialysis-on days compared to dialysis-off days: large amplitude of glycemic excursion level (5.82 ± 2.86 mmol/L versus 4.21 ± 1.71 mmol/L), large amplitude of glycemic excursion level from 8 a.m. to 2 p.m. (3.6 ± 1.74 mmol/L versus 2.8 ± 1.33 mmol/L), mean amplitude of glycemic excursion level (4.78 ± 1.68 mmol/L versus 3.89 ± 1.67 mmol/L), mean amplitude of glycemic excursion level from 8 a.m. to 2 p.m. (4.01 ± 1.03 mmol/L versus 3.12. ± 0.97 mmol/L), standard deviation of blood glucose (1.55 ± 0.89 mmol/L versus 1.03 ± 0.4 mmol/L), and time below a target glucose range of less than 3.9 mmol/L (8.27% versus 4.25%)., Conclusion: Fluctuations in blood glucose levels were larger on dialysis-on days, particularly from the start of hemodialysis to 2 h post-hemodialysis, than on dialysis-off days. Hypoglycemia, as indicated by the time below a target glucose range of less than 3.9 mmol/L, occurred more frequently on dialysis-on days than on dialysis-off days., (© 2022. The Author(s).)

Long non-coding RNA (lncRNA) was reported to be a critical regulator of cellular homeostasis, but poorly understood in idiopathic pulmonary fibrosis (IPF). Here, we systematically identified a crucial lncRNA, p53-induced long non-coding RNA TP53 target 1 (TP53TG1), which was the dysregulated hub gene in IPF regulatory network and one of the top degree genes and down-regulated in IPF-drived fibroblasts. Functional experiments revealed that overexpression of TP53TG1 attenuated the increased expression of fibronectin 1 (Fn1), Collagen 1α1, Collagen 3α1, ACTA2 mRNA, Fn1, and Collagen I protein level, excessive fibroblasts proliferation, migration and differentiation induced by TGF-β1 in MRC-5 as well as PMLFs. In vivo assays identified that forced expression of TP53TG1 by adeno-associated virus 5 (AAV5) not only prevented BLM-induced experimental fibrosis but also reversed established lung fibrosis in the murine model. Mechanistically, TP53TG1 was found to bind to amount of tight junction proteins. Importantly, we found that TP53TG1 binds to the Myosin Heavy Chain 9 (MYH9) to inhibit its protein expression and thus the MYH9-mediated activation of fibroblasts. Collectively, we identified the TP53TG1 as a master suppressor of fibroblast activation and IPF, which could be a potential hub for targeting treatment of the disease., (© 2022. The Author(s).)

Pulmonary fibrosis (PF) is a type of interstitial pneumonia with complex etiology and high mortality, characterized by progressive scarring of the alveolar interstitium and myofibroblastic lesions. Recently, there has been growing appreciation of the importance of long non-coding RNAs (lncRNAs) in organ fibrosis. The aim of this study was to investigate the role of lncRNAs in lung fibrosis. We used a qRT-PCR assay to identify dysregulated lncRNAs in the lungs of mice with experimental, bleomycin (BLM)-induced pulmonary fibrosis, and a series of molecular assays to assess the role of the novel lncRNA NONMMUT060091, designated as pulmonary fibrosis inhibitor (PFI), which was significantly downregulated in lung fibrosis. Functionally, knockdown of endogenous PFI by smart silencer promoted proliferation, differentiation, and extracellular matrix (ECM) deposition in primary mouse lung fibroblasts (MLFs). In contrast, overexpression of PFI partially abrogated TGF-β1-induced fibrogenesis both in MLFs and in the human fetal lung fibroblast MRC-5 cells. Similarly, PFI overexpression attenuated BLM-induced pulmonary fibrosis compared with wild type (WT) mice. Mechanistically, using chromatin isolation by RNA purification-mass spectrometry (ChIRP-MS) and an RNA pull-down assay, PFI was found to directly bind Serine/arginine-rich splicing factor 1 (SRSF1), and to repress its expression and pro-fibrotic activity. Furthermore, silencing of SRSF1 inhibited TGF-β1-induced proliferation, differentiation, and ECM deposition in MRC-5 cells by limiting the formation of the EDA+Fn1 splicing isoform; whereas forced expression of SRSF1 by intratracheal injection of adeno-associated virus 5 (AAV5) ablated the anti-fibrotic effect of PFI in BLM-treated mice. Overall, these data reveal that PFI mitigated pulmonary fibrosis through negative regulation of the expression and activity of SRSF1 to decrease the formation of the EDA+Fn1 splicing isoform, and suggest that PFI and SRSF1 may serve as potential targets for the treatment of lung fibrosis., (© 2021. The Author(s), under exclusive licence to ADMC Associazione Differenziamento e Morte Cellulare.)

Objective To study the therapeutic effect of rapamycin (RAPA) on experimental autoimmune myasthenia gravis (EAMG) rats and to explore the related immune mechanisms. Methods The mouse-derived acetylcholine receptor alpha subunit 97-116 peptide (R97-116) was used to immunize Lewis rats to establish an EAMG rat model. The rats were randomly divided into three groups: complete Freund's adjuvant control group (CFA group), EAMG model control group, and RAPA treatment group [1 mg/(kg.d)]. The Lennon muscle strength scoring scale was used to evaluate rats' clinical symptoms in each group once every two days, and their body mass was recorded. ELISA was performed to detect the level of anti-R97-116 antibodies in the peripheral blood of rats. Flow cytometry was used to detect the numbers of Th17 cells and regulatory T cells (Tregs) in rat splenocytes. Splenocytes were stimulated with 5 μg/mL concanavalin A (ConA), 10 μg/mL R97-116 and RPMI1640 medium, and the proliferation activity of rat splenocytes was tested by CCK-8 assay. Results RAPA treatment significantly improved the body mass and clinical scores in EAMG rats. Compared with the CFA group, the number of Th17 cells in the spleen of the EAMG group increased, and the number of Tregs decreased. Compared with the EAMG group, the number of Th17 cells in the spleen of RAPA-treated rats significantly dropped, the number of Tregs went up, and the level of anti-R97-116 antibodies in the serum went down. RAPA treatment inhibited the proliferation of lymphocytes induced by RPMI1640 medium, R97-116, and ConA stimulation. Conclusion RAPA may alleviate the clinical symptoms of EAMG rats by down-regulating the ratio of Th17 cells/Tregs.

We have developed a new solution-phase chemical reduction method for the synthesis of poly(vinyl alcohol) coated copper nanoparticles in aqueous solution. Copper nitrate is used as the precursor, sodium hypophosphite as the reducing agent, and poly(vinyl alcohol) as the coating agent. The synthesis of copper nanoparticles could be completed within several hours and the copper nanoparticles in powder form could be stored within one week in ambient condition. In Ar atmosphere, the complete thermal decomposition temperature of coated layer was lower than 450 °C. The antioxidative properties of poly(vinyl alcohol) coated copper nanoparticles were evaluated compared to that of polyvinylpyrrolidone coated copper nanoparticles.

The basic theory of high power green laser equipment for prostate hyperplasia therapy and the components of the system developed are introduced. Considering the requirements of the clinical therapy, the working process of the high power green laser apparatus are designed and the laser with stable output at 120 W is achieved. The controlling hardware and application software are developed, and the safety step is designed. The high power green laser apparatus manufactured with characteristics of stable output, multifunctional and friendly interface provides a choices of prostate hyperplasia therapy for using nationalization instrument.