In contrast to the growing interests in studying noncoding RNAs (ncRNAs) such as microRNA (miRNA or miR) pharmacoepigenetics, there is a lack of efficient means to cost effectively produce large ...quantities of natural miRNA agents. Our recent efforts led to a successful production of chimeric pre-miR-27b in bacteria using a transfer RNA (tRNA)-based recombinant RNA technology, but at very low expression levels. Herein, we present a high-yield expression of chimeric pre-miR-1291 in common Escherichia coli strains using the same tRNA scaffold. The tRNA fusion pre-miR-1291 (tRNA/mir-1291) was then purified to high homogeneity using affinity chromatography, whose primary sequence and post-transcriptional modifications were directly characterized by mass spectrometric analyses. Chimeric tRNA/mir-1291 was readily processed to mature miR-1291 in human carcinoma MCF-7 and PANC-1 cells. Consequently, recombinant tRNA/mir-1291 reduced the protein levels of miR-1291 target genes, including ABCC1, FOXA2, and MeCP2, as compared with cells transfected with the same doses of control methionyl-tRNA scaffold with a sephadex aptamer (tRNA/MSA). In addition, tRNA-carried pre-miR-1291 suppressed the growth of MCF-7 and PANC-1 cells in a dose-dependent manner, and significantly enhanced the sensitivity of ABCC1-overexpressing PANC-1 cells to doxorubicin. These results indicate that recombinant miR-1291 agent is effective in the modulation of target gene expression and chemosensitivity, which may provide insights into high-yield bioengineering of new ncRNA agents for pharmacoepigenetics research.
In wild-type phototrophic organisms, carotenoids (Crts) are primarily packed into specific pigment-protein complexes along with chlorophylls or bacteriochlorophylls and play important roles in the ...light reactions of photosynthesis. Diphenylamine (DPA) inhibits carotenogenesis but not phototrophic growth of anoxygenic phototrophs and eliminates virtually all Crts from photosynthetic membranes and photocomplexes. To investigate the effect of Crts on assembly of the reaction center–light-harvesting (RC–LH) complex from the filamentous anoxygenic phototroph Roseiflexus (Rfl.) castenholzii, we generated carotenoidless (abbreviated Crt-less, used here to describe an RC−LH complex whose carotenoid content is greatly reduced but is not zero) RC–LH complexes by growing cells in the presence of DPA. Here we present cryo-electron microscopy structures of the Rfl. castenholzii native and Crt-less RC–LH complexes with resolutions of 2.86 Å and 2.85 Å, respectively. From the high-quality map obtained in this work, several important but previously unresolved details in the Rfl. castenholzii RC–LH structure were determined unambiguously including the assignment and likely function of three small polypeptides, the content and spatial arrangement of Crts with bacteriochlorophyll molecules in the complex. The overall structures of carotenoid-containing and Crt-less complexes are similar. However, structural comparisons showed that only five Crt molecules remain in complexes from DPA-treated cells and that the subunit X (TMx) flanked on the N-terminal helix of the Cyt-subunit is missing. Based on these results, the function of Crts in the assembly of the Rfl. castenholzii RC–LH complex and the molecular mechanism of quinone exchange is discussed. These structural details provide a fresh look at the photosynthetic apparatus of an evolutionary ancient phototroph as well as new insights into the importance of Crts for proper assembly and functioning of the RC–LH complex.
The cure rate of acute lymphoblastic leukemia (ALL) in adolescents and adults remains poor. This study aimed to establish a prognostic model for ≥14-year-old patients with ALL to guide treatment ...decisions. We retrospectively analyzed the data of 321 ALL patients between January 2017 and June 2020. Patients were randomly (2:1 ratio) divided into either the training or validation set. A nomogram was used to construct a prognostic model. Multivariate Cox analysis of the training set showed that age > 50 years, white blood cell count > 28.52×10
9
/L, and MLL rearrangement were independent risk factors for overall survival (OS), while platelet count >37×10
9
/L was an independent protective factor. The nomogram was established according to these independent prognostic factors in the training set, where patients were grouped into two categories: low-risk (≤13.15) and high-risk (>13.15). The survival analysis, for either total patients or sub-group patients, showed that both OS and progression-free survival (PFS) of low-risk patients was significantly better than that of high-risk patients. Moreover, treatment analysis showed that both OS and progression-free survival (PFS) of ALL with stem cell transplantation (SCT) were significantly better than that of ALL without SCT. Further stratified analysis showed that in low-risk patients, the OS and PFS of patients with SCT were significantly better than those of patients without SCT. In contrast, in high-risk patients, compared with non-SCT patients, receiving SCT can only significantly prolong the PFS, but it does not benefit the OS. We established a simple and effective prognostic model for ≥ 14-year-old patients with ALL that can provide accurate risk stratification and determine the clinical strategy.
Plants and natural compounds have been widely recognized to have potential for the prevention of cancer progression and as complementary or standalone treatments for cancer patients. The major ...benefits of natural compounds are their reduced toxicity compared to more aggressive and widely utilized cancer treatment approaches. Preclinical studies have led to the discovery of a number of natural anticancer compounds, including preparations of Vitex negundo L., green tea, mandarin peel oil, ursolic acid, curcumin and resveratrol. Although the in vitro data highlights the potential of these natural alternatives, their benefits in clinical cancer treatment remain less conclusive. In this review, we will discuss some of the recent advances in natural anticancer treatment discovery for the four most prominent global cancers, namely, breast, lung, prostate and skin metastases. As the exploration of natural therapeutics continues to expand, these substances have the potential to be utilized as preventative strategies and complimentary therapeutics. In some cases, they may have sufficient anti-tumor and anti-carcinogenic properties to function as standalone cancer treatments.
Restriction of pollen germination before the pollen grain is pollinated to stigma is essential for successful fertilization in angiosperms. However, the mechanisms underlying the process remain ...poorly understood. Here, we report functional characterization of the MAPKKK kinases, MAP3Kε1 and MAP3Kε2, involve in control of pollen germination in Arabidopsis. The two genes were expressed in different tissues with higher expression levels in the tricellular pollen grains. The
double mutation caused abnormal callose accumulation, increasing level of JA and precocious pollen germination, resulting in significantly reduced seed set. Furthermore, the
double mutations obviously upregulated the expression levels of genes in JA biosynthesis and signaling. The MAP3Kε1/2 interacted with MOB1A/1B which shared homology with the core components of Hippo singling pathway in yeast. The Arabidopsis
mutant also exhibited a similar phenotype of precocious pollen germination to that in
mutants. Taken together, these results suggested that the MAP3Kεs interacted with MOB1s and played important role in restriction of the precocious pollen germination, possibly through crosstalk with JA signaling and influencing callose accumulation in Arabidopsis.
Abstract
Background
Treatment options for pregnant women with immune thrombocytopenia (ITP) who do not respond to first-line treatment are limited. Few studies have reported the use of recombinant ...human thrombopoietin (rhTPO) for this subset of patients.
Aims
To investigate the efficacy and safety of rhTPO in ITP during pregnancy and determine obstetric outcomes and predictors of treatment response.
Methods
From July 2013 to October 2022, the data of 81 pregnant women with ITP and a platelet count < 30 × 10
9
/L who did not respond to steroids and/or intravenous immunoglobulin were retrospectively analysed. Of these patients, 33 received rhTPO treatment (rhTPO group) while 48 did not (control group). Baseline characteristics, haematological disease outcomes before delivery, obstetric outcomes, and adverse events were compared between groups. In the rhTPO group, a generalised estimating equation (GEE) was used to investigate the factors influencing the response to rhTPO treatment.
Results
The baseline characteristics were comparable between both groups (
P
> 0.05, both). Compared with controls, rhTPO patients had higher platelet counts (median interquartile range: 42 21.5–67.5 vs. 25 19–29 × 10
9
/L,
P
= 0.002), lower bleeding rate (6.1% vs. 25%,
P
= 0.027), and lower platelet transfusion rate before delivery (57.6% vs. 97.9%,
P
< 0.001). Gestational weeks of delivery (37.6 37–38.4 vs 37.1 37–37.2 weeks,
P
= 0.001) were longer in the rhTPO group than in the control group. The rates of caesarean section, postpartum haemorrhage, foetal or neonatal complications, and complication types in both groups were similar (all
P
> 0.05). No liver or renal function impairment or thrombosis cases were observed in the rhTPO group. GEE analysis revealed that the baseline mean platelet volume (MPV) (odds ratio OR: 0.522,
P
= 0.002) and platelet-to-lymphocyte ratio (PLR) (OR: 1.214,
P
= 0.025) were predictors of response to rhTPO treatment.
Conclusion
rhTPO may be an effective and safe treatment option for pregnancies with ITP that do not respond to first-line treatment; it may have slightly prolonged the gestational age of delivery. Patients with a low baseline MPV and high baseline PLR may be more responsive to rhTPO treatment. The present study serves as a foundation for future research.
Purpose
A relationship between albuminuria and obstructive sleep apnea (OSA) has been documented in previous studies. Nevertheless, the impact of continuous positive airway pressure (CPAP) treatment ...on albuminuria in subjects with OSA is debated. This meta-analysis was carried out to investigate whether or not CPAP treatment affected urinary albumin-to-creatinine ratio (UACR) in subjects with OSA.
Methods
A comprehensive literature search was conducted on Web of Science, Embase, and PubMed from January 1990 to December 2020. Information on patients’ characteristics, features of the studies, and UACR of pre- and post-CPAP treatment was collected. For estimation of the pooled effects, standardized mean difference (SMD) was applied.
Results
This meta-analysis included 6 articles and 211 subjects. The pooled analysis suggested that CPAP therapy exerted a favorable effect on the decrease of UACR in subjects with OSA (SMD = 0.415, 95% CI = 0.026 to 0.804, z = 2.09,
p
= 0.037). Subgroup analyses revealed that the CPAP treatment effect was not influenced by sample size, BMI, age, or AHI.
Conclusion
The present meta-analysis indicated that UACR was significantly reduced by CPAP therapy in subjects with OSA. Further well-designed randomized controlled trials with large sample size are required to confirm the benefits.
3D-HEVC (The 3D Extension of High Efficiency Video Coding) is the newest 3D video coding standard, which enriches multimedia applications with the video format of multi-view plus depth. For the depth ...map coding in 3D-HEVC, the advanced coding tools enhance the coding efficiency of the depth map and the quality of the synthesized view. However, the time consumption and complexity of 3D-HEVC also increase significantly. This paper utilizes the characteristics of human visual system to propose a fast algorithm based on visual perception for the acceleration of the depth intra coding of 3D-HEVC. The depth map is segmented into different regions by Otsu's auto-thresholding. The dominate edge direction is categorized for each prediction unit. We detect the perceptual edge based on just noticeable depth difference model to extract the area that may affect the visual perception. According to depth map segmentation and edge distribution, we reduce the corresponding intra angular modes and determine whether to perform depth modelling mode. We also incorporate the boundary continuity and rate-distortion cost thresholding to propose the fast coding unit decision. The experimental results show that the proposed algorithm eliminates 53.09% of the depth coding time with only 0.15% BD-BR on average. The coding performance of the proposed algorithm outperforms the previous works significantly.
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