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Hepatocellular carcinoma patients together with site vein thrombosis helped by robotic radiosurgery: Meantime connection between a prospective review.
Lophotrichous bacteria swim through fluid by rotating their flagellar bundle extended collectively from one pole of the cell body. Cells experience modes of motility such as push, pull, and wrapping, accompanied by pauses of motor rotation in between. We present a mathematical model of a lophotrichous bacterium and investigate the hydrodynamic interaction of cells to understand their swimming mechanism. Cpd 20m mw We classify the swimming modes which vary depending on the bending modulus of the hook and the magnitude of applied torques on the motor. Given the hook's bending modulus, we find that there exist corresponding critical thresholds of the magnitude of applied torques that separate wrapping from pull in CW motor rotation, and overwhirling from push in CCW motor rotation, respectively. We also investigate reoriented directions of cells in three-dimensional perspectives as the cell experiences different series of swimming modes. Our simulations show that the transition from a wrapping mode to a push mode and pauses in between are key factors to determine a new path and that the reoriented direction depends upon the start time and duration of the pauses. It is also shown that the wrapping mode may help a cell to escape from the region where the cell is trapped near a wall.A three-dimensional granular gas of ellipsoids is established by exposing the system to the microgravity environment of the International Space Station. We use two methods to measure the dynamics of the constituent particles and report the long-time development of the granular temperature until no further particle movement is detectable. The resulting cooling behavior can be well described by Haff's cooling law with time scale τ. Different analysis methods show evidence of particle clustering towards the end of the experiment. By using the kinetic theory for ellipsoids we compare the translational energy dissipation of individual collision events with the overall cooling time scale τ. The difference from this comparison indicates how energy is distributed in different degrees of freedom including both translation and rotation during the cooling.RNA modifications are important regulatory elements of RNA functions. However, most genome-wide mapping of RNA modifications has focused on messenger RNAs and transfer RNAs, but such datasets have been lacking for small RNAs. Here we mapped N1-methyladenosine (m1A) in the cellular small RNA space. Benchmarked with synthetic m1A RNAs, our workflow identified specific groups of m1A-containing small RNAs, which are otherwise disproportionally under-represented. In particular, 22-nucleotides long 3' tRNA-fragments are highly enriched for TRMT6/61A-dependent m1A located within the seed region. TRMT6/61A-dependent m1A negatively affects gene silencing by tRF-3s. In urothelial carcinoma of the bladder, where TRMT6/61A is over-expressed, higher m1A modification on tRFs is detected, correlated with a dysregulation of tRF targetome. Lastly, TRMT6/61A regulates tRF-3 targets involved in unfolded protein response. Together, our results reveal a mechanism of regulating gene expression via base modification of small RNA.Macular degeneration is a leading cause of blindness. Treatments to rescue vision are currently limited. Here, we study how loss of central vision affects lateral feedback to spared areas of the human retina. We identify a cone-driven gain control mechanism that reduces visual function beyond the atrophic area in macular degeneration. This finding provides an insight into the negative effects of geographic atrophy on vision. Therefore, we develop a strategy to restore this feedback mechanism, through activation of laterally projecting cells. This results in improved vision in Cnga3-/- mice, which lack cone function, as well as a mouse model of geographic atrophy. Our work shows that a loss of lateral gain control contributes to the vision deficit in macular degeneration. Furthermore, in mouse models we show that lateral feedback can be harnessed to improve vision following retinal degeneration.Chronic myeloid leukemia (CML) are initiated and sustained by self-renewing malignant CD34+ stem cells. Extensive efforts have been made to reveal the metabolic signature of the leukemia stem/progenitor cells in genomic, transcriptomic, and metabolomic studies. However, very little proteomic investigation has been conducted and the mechanism regarding at what level the metabolic program was rewired remains poorly understood. Here, using label-free quantitative proteomic profiling, we compared the signature of CD34+ stem/progenitor cells collected from CML individuals with that of healthy donors and observed significant changes in the abundance of enzymes associated with aerobic central carbonate metabolic pathways. Specifically, CML stem/progenitor cells expressed increased tricarboxylic acid cycle (TCA) with decreased glycolytic proteins, accompanying by increased oxidative phosphorylation (OXPHOS) and decreased glycolysis activity. Administration of the well-known OXPHOS inhibitor metformin eradicated CML stem/progenitor cells and re-sensitized CD34+ CML cells to imatinib in vitro and in patient-derived tumor xenograft murine model. However, different from normal CD34+ cells, the abundance and activity of OXPHOS protein were both unexpectedly elevated with endoplasmic reticulum stress induced by metformin in CML CD34+ cells. The four major aberrantly expressed protein sets, in contrast, were downregulated by metformin in CML CD34+ cells. These data challenged the dependency of OXPHOS for CML CD34+ cell survival and underlined the novel mechanism of metformin. More importantly, it suggested a strong rationale for the use of tyrosine kinase inhibitors in combination with metformin in treating CML.Metabolic disorders and abnormal immune function changes occur in tumor tissues and cells to varying degrees. There is increasing evidence that reprogrammed energy metabolism contributes to the development of tumor suppressive immune microenvironment and influences the course of gastric cancer (GC). Current studies have found that tumor microenvironment (TME) also has important clinicopathological significance in predicting prognosis and therapeutic efficacy. Novel approaches targeting TME therapy, such as immune checkpoint blockade (ICB), metabolic inhibitors and key enzymes of immune metabolism, have been involved in the treatment of GC. However, the interaction between GC cells metabolism and immune metabolism and how to make better use of these immunotherapy methods in the complex TME in GC are still being explored. Here, we discuss how metabolic reprogramming of GC cells and immune cells involved in GC immune responses modulate anti-tumor immune responses, as well as the effects of gastrointestinal flora in TME and GC. It is also proposed how to enhance anti-tumor immune response by understanding the targeted metabolism of these metabolic reprogramming to provide direction for the treatment and prognosis of GC.Despite several decades of intense research focused on understanding function(s) and disease-associated malfunction of p53, there is no sign of any "mid-life crisis" in this rapidly advancing area of biomedicine. Firmly established as the hub of cellular stress responses and tumor suppressor targeted in most malignancies, p53's many talents continue to surprise us, providing not only fresh insights into cell and organismal biology, but also new avenues to cancer treatment. Among the most fruitful lines of p53 research in recent years have been the discoveries revealing the multifaceted roles of p53-centered pathways in the fundamental processes of DNA replication and ribosome biogenesis (RiBi), along with cellular responses to replication and RiBi stresses, two intertwined areas of cell (patho)physiology that we discuss in this review. Here, we first provide concise introductory notes on the canonical roles of p53, the key interacting proteins, downstream targets and post-translational modifications involved er cells are addicted due to their aberrant DNA replication, repair, and proteo-synthesis demands.Definite cure remains exceptional in myeloma patients even after high-dose chemotherapy (HDCT) with melphalan (Mel) and autologous stem cell transplantation (ASCT). Thus, improving efficacy of HDCT in MM remains an unresolved issue. This randomized phase II trial compared standard 200 mg/m2 Mel HDCT to experimental HDCT with 200 mg/m2 bendamustine, given both at days -4 and -3, combined with 100 mg/m2 melphalan at days -2 and -1 (BenMel) before ASCT as first-line consolidation in myeloma patients. The primary endpoint aimed to identify at least a 15% improvement in the complete remission rate (stringent CR + CR) after HDCT with BenMel compared with Mel alone. A total of 120 MM patients were 11 randomized. The rate of sCR/CR after ASCT was higher in BenMel than in Mel treated patients (70.0% vs. 51.7%; p = 0.039). Three patients in the BenMel group (5.0%) had reversible acute renal insufficiency compared with none in Mel patients. Minimal residual disease negativity ( less then 10-5) by flow cytometry was observed in 26 (45.6%) BenMel patients and 22 (37.9%) in the Mel group (p = 0.375). Our data suggest that BenMel HDCT is safe and improves the sCR/CR rate compared with standard Mel alone.The burden of cancer diseases is increasing every year, therefore, the demands to figure out novel drugs that can retain antitumor properties have been raised. This study aimed to investigate the anti-tumor properties of amygdalin (Amy) against Ehrlich ascites carcinoma (EAC) bearing mice and its protective properties against liver damage. Amy and the standard anticancer drug Sorafenib (Sor) were given alone or in combination to Swiss albino female mice that had been injected with EAC cells. Biochemical parameters of liver function (AST, ALT, GGT, total protein, albumin), tumor volume, oxidative stress [malondialdehyde, (MDA)] and antioxidative [superoxide dismutase (SOD), and reduced glutathione (GSH)] markers were measured. The hepatic expression of the antioxidant-related gene [nuclear factor erythroid-2-related factor 2 (Nrf2)], the migration-related gene [matrix metalloprotease 9 (MMP9)], and the angiogenesis-related gene [vascular endothelial growth factor (VEGF)] were evaluated by qPCR. The results revealed that EAC-bearing mice treated with Amy and/or Sor showed a decrease in the tumor burden and hepatic damage as evidenced by (1) decreased tumor volume, number of viable tumor cells; (2) increased number of dead tumor cells; (3) restored the liver function parameters; (4) reduced hepatic MDA levels; (5) enhanced hepatic GSH and SOD levels; (6) upregulated expression of Nrf2; (7) downregulated expression of MMP9 and VEGF, and (8) improved hepatic structure. Among all treatments, mice co-treated with Amy (orally) and Sor (intraperitoneally) showed the best effect. With these results, we concluded that the Amy improved the antitumor effect of Sor and had a protective role on liver damage induced by EAC in mice.Personalized modeling has long been anticipated to approach precise noninvasive blood glucose measurements, but challenged by limited data for training personal model and its unavoidable outlier predictions. To overcome these long-standing problems, we largely enhanced the training efficiency with the limited personal data by an innovative Deduction Learning (DL), instead of the conventional Induction Learning (IL). The domain theory of our deductive method, DL, made use of accumulated comparison of paired inputs leading to corrections to preceded measured blood glucose to construct our deep neural network architecture. DL method involves the use of paired adjacent rounds of finger pulsation Photoplethysmography signal recordings as the input to a convolutional-neural-network (CNN) based deep learning model. Our study reveals that CNN filters of DL model generated extra and non-uniform feature patterns than that of IL models, which suggests DL is superior to IL in terms of learning efficiency under limited training data.
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