Strawberry plants require light for growth, but the frequent occurrence of low-light weather in winter can lead to a decrease in the photosynthetic rate (Pn) of strawberry plants. Light-emitting ...diode (LED) systems could be used to increase Pn. However, the changes in the phytohormones and transcriptomic reprogramming in strawberry leaves under different light qualities are still unclear. In this study, we treated strawberry plants with sunlight, sunlight covered with a 50% sunshade net, no light, blue light (460 nm), red light (660 nm), and a 50% red/50% blue LED light combination for 3 days and 7 days. Our results revealed that the light quality has an effect on the contents of Chl a and Chl b, the minimal fluorescence (F
), and the Pn of strawberry plants. The light quality also affected the contents of abscisic acid (ABA), auxin (IAA),
-zeatin-riboside (
Z), jasmonic acid (JA), and salicylic acid (SA). RNA sequencing (RNA-seq) revealed that differentially expressed genes (DEGs) are significantly enriched in photosynthesis antenna proteins, photosynthesis, carbon fixation in photosynthetic organisms, porphyrin and chlorophyll metabolisms, carotenoid biosynthesis, tryptophan metabolism, phenylalanine metabolism, zeatin biosynthesis, and linolenic acid metabolism. We then selected the key DEGs based on the results of a weighted gene co-expression network analysis (WGCNA) and drew nine metabolic heatmaps and protein-protein interaction networks to map light regulation.
The morbidity and mortality rates of ischemic stroke (IS) are very high, and IS constitutes one of the main causes of disability and death worldwide. The pathogenesis of ischemic stroke includes ...excitotoxicity, calcium overload, oxygen radical injury, inflammatory reactions, necrosis/apoptosis, destruction of the blood-brain barrier (BBB), and other pathologic processes. Recent studies have shown that exosomes are critical to the pathogenesis, diagnosis, and treatment of cerebral infarctions resulting from ischemic stroke; and there is growing interest in the role of exosomes and exosomal miRNAs in the diagnosis and treatment of IS. Exosomes from central nervous system cells can be found in cerebrospinal fluid and peripheral bodily fluids, and exosomal contents have been reported to change with disease occurrence. Exosomes are small membranous extracellular vesicles (EVs), 30-150 nm in diameter, that are released from the cell membrane into the depressions that arise from the membranes of multivesicular bodies. Exosomes carry lipids, proteins, mRNAs, and microRNAs (miRNAs) and transport information to target cells. This exosomal transfer of functional mRNAs/miRNAs and proteins ultimately affects transcription and translation within recipient cells. Exosomes are EVs with a double-membrane structure that protects them from ribonucleases in the blood, allowing exosomal miRNAs to be more stable and to avoid degradation. New evidence shows that exosomes derived from neural cells, endothelial cells, and various stem cells create a fertile environment that supports the proliferation and growth of neural cells and endothelial cells, inhibits apoptosis and inflammatory responses, and promotes angiogenesis. In the present review, we discuss how circulating exosomes-and exosomal miRNAs in particular-may provide novel strategies for the early diagnosis and treatment of ischemic stroke via their potential as non-invasive biomarkers and drug carriers.
The plasmid-borne fosfomycin resistance gene fosA3 has been identified in Escherichia coli (E. coli) from various animals but has rarely been reported in ducks. In this study, we investigated the ...fosA3 prevalence and molecular characteristics of fosA3-harboring E. coli strains from ducks in Shandong province of China. In 416 E. coli isolates, 91 (21.88%) were identified as fosA3-bearing strains, and the fosfomycin-resistant phenotype of 88 of the 91 fosA3-harboring strains was successfully transferred to the recipient strains. Seven different genetic structures surrounding the fosA3 gene were detected and 2 new contexts were discovered among the fosA3-carrying E. coli. Twenty fosA3-harboring isolates and their trans-conjugants were randomly selected for pulsed-field gel electrophoresis (PFGE) typing and S1-nuclease PFGE, respectively. The PFGE patterns revealed that the 20 randomly selected fosA3-bearing isolates were not a result of clonal dissemination. S1-PFGE showed that 15 of the 20 randomly selected trans-conjugants carried a single plasmid, and these 15 plasmids that harbored fosA3 (55–190 kb) were distributed into the following replicon types: IncF (n = 11), IncI1 (n = 1), IncN (n = 1), untypable (n = 1), and W-FIC (n = 1). Additionally, as vectors for fosA3 in E. coli, F-:A1:B6, N/ST1, IncI1/ST2, W-FIC, and one untypable plasmid had never been reported before. These observations highlighted the importance of ducks as a reservoir for multidrug-resistant fosA3-carrying E. coli.
Lymph nodes (LNs) are peripheral lymphoid organs essential for vaccine-induced immune responses. Although cationic liposomes have been documented as a novel adjuvant and vaccine delivery system, ...whether enhancing LN targeting would improve the efficiency of cationic liposome-formulated vaccines has not been elucidated yet. In the present study we investigated the effect of PEGylation on LN targeting and the immunogenicity of cationic liposome-formulated vaccines. DOTAP cationic liposomes were incorporated with 1 or 5mol% of DSPE-PEG2000 and labeled with near infrared fluorescent dyes. The lymphatic trafficking and biodistribution of different liposomes after subcutaneous (s.c.) injection were recorded using an in-vivo imaging system. The results showed that incorporation of 1mol% DSPE-PEG2000 not only accelerated the drainage of DOTAP liposomes into draining LNs, but also prolonged their LN retention and enhanced liposome uptake by resident antigen-presenting cells. On the other hand, although incorporating 5mol% of DSPE-PEG2000 into DOTAP liposomes enhanced their LN retention and uptake to a lesser extent, it prolonged blood circulation of DOTAP liposomes and increased their splenic accumulation. In addition, PEGylated DOTAP liposomes augmented primary and secondary anti-OVA antibody responses more potently than nonPEGylated DOTAP liposomes did. Hence, incorporating a small amount of DSPE-PEG2000 into DOTAP liposomes not only increased the passive LN targeting of DOTAP-formulated vaccines but also modulated their biodistribution in vivo, which consequently improved the efficiency of cationic liposome-formulated vaccines.
Incorporation of DSPE-PEG2000 not only enhanced passive lymph-node targeting of DOTAP liposomes but also increased their splenic accumulation, which consequently augmented the efficiency of DOTAP-formulated vaccines. Display omitted
PARP-1 is an abundant nuclear enzyme that modifies substrates by poly(ADP-ribose)-ylation. PARP-1 has well-described functions in DNA damage repair and also functions as a context-specific regulator ...of transcription factors. With multiple models, data show that PARP-1 elicits protumorigenic effects in androgen receptor (AR)-positive prostate cancer cells, in both the presence and absence of genotoxic insult. Mechanistically, PARP-1 is recruited to sites of AR function, therein promoting AR occupancy and AR function. It was further confirmed in genetically defined systems that PARP-1 supports AR transcriptional function, and that in models of advanced prostate cancer, PARP-1 enzymatic activity is enhanced, further linking PARP-1 to AR activity and disease progression. In vivo analyses show that PARP-1 activity is required for AR function in xenograft tumors, as well as tumor cell growth in vivo and generation and maintenance of castration resistance. Finally, in a novel explant system of primary human tumors, targeting PARP-1 potently suppresses tumor cell proliferation. Collectively, these studies identify novel functions of PARP-1 in promoting disease progression, and ultimately suggest that the dual functions of PARP-1 can be targeted in human prostate cancer to suppress tumor growth and progression to castration resistance.
These studies introduce a paradigm shift with regard to PARP-1 function in human malignancy, and suggest that the dual functions of PARP-1 in DNA damage repair and transcription factor regulation can be leveraged to suppress pathways critical for promalignant phenotypes in prostate cancer cells by modulation of the DNA damage response and hormone signaling pathways. The combined studies highlight the importance of dual PARP-1 function in malignancy and provide the basis for therapeutic targeting.
Xingnaojing (XNJ) injection, an extract derived from traditional Chinese medicine, is commonly used to treat ischemic stroke (IS). Previous studies have shown that XNJ has the ability to alleviate ...apoptosis in cerebral ischemia-reperfusion injury. However, the potential mechanisms have not been clarified.
To identify the neuroprotective effect of XNJ and explore whether XNJ inhibits cell apoptosis associated with endoplasmic reticulum stress (ERS) after IS.
In this study, cultured hippocampal neurons from mouse embryos and Sprague-Dawley rats were assigned randomly to four groups: sham, model, XNJ, and edaravone. The treatment groups were administered 2 h after modelling. Neurological deficit scores and motor performance tests were performed after 24 h of modelling. Additionally, pathomorphology, cell apoptosis and calcium content were evaluated. To ascertain the expression of ERS proteins, western blotting and polymerase chain reaction were employed.
The results indicated that XNJ treatment resulted in a notable decrease in infarct volume, apoptosis and missteps compared with the model group. XNJ also exhibited improvements in neurological function, grip strength and motor time. The calcium content significantly reduced in XNJ group. The XNJ administration resulted in a reduction in the levels of proteins associated with ERS including CHOP, GRP78, Bax, caspase-12, caspase-9, and cleaved-caspase-3, but an increase of the Bcl-2/Bax ratio. Furthermore, the downregulation of mRNA expression of CHOP, GRP78, caspase-12, caspase-9, and caspase-3 was confirmed in both cultured neurons and rat model.
These findings suggest that XNJ may alleviate apoptosis by modulating the ERS-induced apoptosis pathway, making it a potential novel therapeutic approach for ischemic stroke.
Objective
Our study aimed to investigate the glucose levels in PD and controls. We also examine whether glucose control is associated with PD severity regardless of diabetic status, and test whether ...the correlation is mediated by cerebral small vessel disease (CSVD) burden.
Methods
A total of 100 patients with idiopathic PD and 100 age‐ and sex‐matched controls who underwent brain magnetic resonance imaging (MRI) were enrolled in this study. We collected the clinical data and blood parameters, including fasting blood glucose (FBG), glycated hemoglobin A1c (HbA1c), and blood lipid. Patients with PD were divided into early (n = 61) and advanced (n = 39) subgroups, based on Hoehn and Yahr (H&Y) stages. Differences between the PD and controls, PD with and without diabetes, and between two PD subgroups were compared. CSVD markers were assessed, including lacunes, white matter hyperintensities, enlarged perivascular spaces, and cerebral microbleeds. Multivariable logistic regressions were used to test the association between HbA1c and H&Y stages. Interaction between HbA1c and CSVD burden in relation to H&Y stages was also analyzed.
Results
PD group exhibited higher HbA1c (p < 0.001), lower high‐density lipoprotein cholesterol (p < 0.001) and triglyceride (p = 0.049) than controls. Advanced PD patients showed higher HbA1c than early PD group (p = 0.022). Increasing HbA1c (OR = 1.54, 95% CI 1.03–2.32, p = 0.036) along with longer disease duration (OR = 1.14, 95% CI 1.01–1.27, p = 0.028) and higher UPDRS III score (OR = 1.07, 95% CI 1.02–1.11, p = 0.002) increased the risk of belonging to the higher H&Y stage. However, interaction between HbA1c and CSVD burden in relation to H&Y stages was not significant.
Interpretation
HbA1c is independently associated with H&Y stages in PD, and this correlation may not be mediated by CSVD burden.
Brain activity is time varying and dynamic, even in the resting state. However, little attention has been paid to the dynamic alterations in regional brain activity in Parkinson's disease (PD). We ...aimed to test for differences in dynamic regional homogeneity (dReHo) between PD patients and healthy controls (HCs) and to further investigate the pathophysiological meaning of this altered dReHo in PD. We included 57 PD patients and 31 HCs with rs-fMRI scans and neuropsychological examinations. Then, ReHo and dReHo were calculated for all subjects. We compared ReHo and dReHo between PD patients and HCs and then analyzed the associations between altered dReHo variability and clinical/neuropsychological measurements. Support vector machines (SVMs) were also used to assist in differentiating PD patients from HCs using the classification values of dReHo. The results showed that PD patients had increased ReHo in the bilateral medial temporal lobe and decreased ReHo in the right posterior cerebellar lobe, right precentral gyrus, and supplementary motor area, compared with controls. The coefficient of variation (CV) of dReHo was considerably higher in the precuneus in PD patients compared with HCs, and the CV of dReHo in the precuneus was found to be highly associated with HAMD, HAMA, and NMSQ scores. Multiple linear regression analysis controlling for demographic, clinical, and neuropsychiatric variables confirmed the association between altered dReHo and HAMD. Using the leave-one-out cross validation procedure, 98% (
< 0.001) of individuals were properly identified using the SVM classifier. These results provide new evidence for the aberrant resting-state brain activity in the precuneus of PD patients and its role in neuropsychiatric symptoms in PD.
Colistin has been used as a growth promotant in livestock feed for many years. In China, mcr-1-positive Escherichia coli strains have been isolated from humans, chickens, and pigs. To date, there are ...few reports about the prevalence and molecular characteristics of fecal E. coli bearing mcr-1 in the meat ducks. In this study, the prevalence of mcr-1 gene was investigated among 120 fecal E. coli strains isolated from healthy meat ducks in Shandong province of China between October 2017 and February 2018. A total of nine mcr-1-containing E. coli strains were identified and two were identified as extra-intestinal pathogenic E. coli (ExPEC) among them. The clonal relationship of the nine E. coli strains was determined by multilocus sequencing typing (MLST) and pulsed field gel electrophoresis (PFGE), and the results indicated that all mcr-1-carrying isolates were clonally unrelated. Two different genetic contexts of mcr-1 were identified among these isolates. Colistin-resistant phenotype of all the isolates was successfully transferred to the recipient strains by conjugation experiments and seven transconjugants carried a single plasmid. The mcr-1 was located on three replicon plasmids: IncI2 (n = 4), IncFII (n = 2) and IncN (n = 1). Complete sequence analysis of a representative plasmid pTA9 revealed that it was strikingly similar with plasmid pMCR1-IncI2 of E. coli, plasmid pHNSHP45 of E. coli, and plasmid pWF-5-19C of Cronobacter sakazakii, implying that pTA9-like plasmids may be epidemic plasmids that mediate the spread of mcr-1 among Enterobacteriaceae. These results highlight that healthy meat duck is a potential reservoir for multidrug resistant mcr-1-containing E. coli strains.
We previously showed that pirfenidone, an anti-fibrotic agent, reduces lung allograft injury or rejection. In this study, we tested the hypothesis that pirfenidone has immune modulating activities ...and evaluated its effects on the function of T-cell subsets, which play important roles in allograft rejection.
We first evaluated whether pirfenidone alters T-cell proliferation and cytokine release in response to T-cell receptor (TCR) activation, and whether pirfenidone alters regulatory T cells (CD4CD25) suppressive effects using an in vitro assay. Additionally, pirfenidone effects on alloantigen-induced T-cell proliferation in vivo were assessed by adoptive transfer of carboxyfluorescein diacetate succinimidyl ester-labeled T cells across a parent->F1 major histocompatibility complex mismatch, as well as using a murine heterotopic cardiac allograft model (BALB/c->C57BL/6).
Pirfenidone was found to inhibit the responder frequency of TCR-stimulated CD4 cell total proliferation in vitro and in vivo, whereas both CD4 and CD8 proliferation index were reduced by pirfenidone. Additionally, pirfenidone inhibited TCR-induced production of multiple pro-inflammatory cytokines and chemokines. Interestingly, there was no change on transforming growth factor-beta production by purified T cells, and pirfenidone had no effect on the suppressive properties of naturally occurring regulatory T cells. Pirfenidone alone showed a small but significant (P<0.05) effect on the in vivo allogeneic response, whereas the combination of pirfenidone and low dose rapamycin had more remarkable effect in reducing the alloantigen response with prolonged graft survival.
Pirfenidone may be an important new agent in transplantation, with particular relevance to combating chronic rejection by inhibiting both fibroproliferative and alloimmune responses.
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