BackgroundThe goal of this study was to delineate the patterns of distant metastasis from colon adenocarcinoma (CAC) and evaluate the survival differences by metastatic patterns.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) database, we extracted patients diagnosed with stage IV CAC between 2010 and 2016. Kaplan‐Meier survival curves were plotted with log‐rank tests to compare overall survival (OS) of patients with different metastatic patterns. Univariate and multivariate Cox proportional hazards regression models were used to evaluate the effects of different metastatic patterns on survival outcomes in terms of OS and disease‐specific survival (DSS).ResultsA total of 26 170 patients were analyzed. The 3‐ and 5‐year OS were 20.7% and 10.5%, respectively, for patients with stage IV CAC. The most common distant metastatic site was the liver, followed by the lung, bone, and brain, but the frequency differed greatly by histology subtypes. The site of metastasis was a significant prognostic factor for OS and DSS in patients with stage IV CAC, independent of the number of metastatic sites and other clinical and demographic prognostic factors. Using liver‐only metastasis as reference, lung‐only metastasis was associated with better OS (hazard ratio [HR] = 0.82, 95% confidence interval [CI], 0.71‐0.94) and DSS (HR = 0.75, 95% CI, 0.64‐0.88). Older age, black race, unmarried status, grade III/IV tumors, advanced tumor‐node‐metastasis (TNM) stage, proximal colon, elevated preoperative carcinoembryonic antigen (CEA), no surgery of the primary site, and no chemotherapy were independent predictors of poor OS.ConclusionsThe site of distant metastasis and number of metastasis site were independent prognostic factors for survival of patients with stage IV CAC. This study highlights the need for diverse treatment strategies for patients with different metastatic patterns.

A new multiphoton upconversion process for rare earth oxide powders is reported, using infrared laser diodes. In vacuum, multiphoton excitation produces intense upconversion emission in the visible spectral range, and Tm(2)O(3) or Yb(2)O(3) achieves pure white upconversion using 808 or 975 nm excitation, respectively.

alternatives to next-generation batteries, have attracted extensive attention due to their high energy density and low cost. Metallic Li is considered as the ultimate choice of anode material for LMBs, owing to its ultrahigh theoretical capacity (3860 mAh g −1 ) and lowest electrochemical potential (−3.04 V vs the standard hydrogen electrode), [2] LMBs were pioneered during the 1970s, but they have not been successfully commercialized due to the significant safety concerns [3][4][5] associated with Li-dendrite growth during the repeated Li plating/ stripping process. The challenges of commercial application of metallic Li anodes can be summarized as follows: 1) Li tends to deposit unevenly to form dendritic and mossy-like morphology on the electrode during electrochemical cycling, which can subsequently penetrate the separator and cause internal short-circuits and thermal runaway. The dendritic Li could also be isolated from the bulk Li or current collector during the stripping process, becoming "dead Li" due to the absence of electronic contact, which leads to increased resistance, fading capacity, and short cycle life. [6] 2) The side reaction between Li and liquid electrolyte results in the formation of a solid electrolyte interphase (SEI) layer on the electrode surface. The unstable SEI layer is very fragile and easily fractured during the Li plating/stripping process. As a result, fresh Li is exposed and further consumes more electrolyte to form new SEI. This repetitive process endlessly consumes both Li and electrolyte, leading to growing interfacial resistance and decreasing Coulombic efficiency (CE). [7] 3) Owing to its "hostless" nature, Li metal undergoes a relatively infinite volume change during electrochemical cycling. This phenomenon causes significant challenges as it can often cause damage to the SEI during plating/stripping. [3] Among all the challenges of the Li-metal anode, the SEI plays a crucial role as a passivation layer to prevent further reactions between Li and electrolyte, hence improving electrochemical performance. A self-formed SEI is generally composed of the stacking of many small domains, including LiF, Li 2 O, Li 2 CO 3 , and organic Li compounds, with heterogeneous composition, ionic conductivities, and mechanical properties. [8] However, the deposition of dendritic or mossy-like Li still occurs during Metallic Li is considered as one of the most promising anode materials for next-generation batteries due to its high theoretical capacity and low electrochemical potential. However, its commercialization has been impeded by the severe safety issues associated with Li-dendrite growth. Non-uniform Li-ion flux on the Li-metal surface and the formation of unstable solid electrolyte interphase (SEI) during the Li plating/stripping process lead to the growth of dendritic and mossy Li structures that deteriorate the cycling performance and can cause short-circuits. Herein, an ultrathin polymer film of "polyurea" as an artificial SEI layer for Li-metal anodes via molecular-layer deposit...

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Cell cycle G 1 exit is a critical stage where cells commonly commit to proliferate or to differentiate, but the biochemical events that regulate the proliferation/differentiation (P/D) transition at G 1 exit are presently unclear. We previously showed that MAT1 (mé nage à trois 1), an assembly factor and targeting subunit of the cyclin-dependent kinase (CDK)-activating kinase (CAK), modulates CAK activities to regulate G 1 exit. Here we find that the retinoid-induced G 1 arrest and differentiation activation of cultured human leukemic cells are associated with a switch to CAK hypophosphorylation of retinoic acid receptor ␣ (RAR␣) from CAK hyperphosphorylation of RAR␣. The switch to CAK hypophosphorylation of RAR␣ is accompanied by decreased MAT1 expression and MAT1 fragmentation that occurs in the differentiating cells through the all-trans-retinoic acid (ATRA)-mediated proteasome degradation pathway. Because HL60R cells that harbor a truncated ligand-dependent AF-2 domain of RAR␣ do not demonstrate any changes in MAT1 levels or CAK phosphorylation of RAR␣ following ATRA stimuli, these biochemical changes appear to be mediated directly through RAR␣. These studies indicate that significant changes in MAT1 levels and CAK activities on RAR␣ phosphorylation accompany the ATRA-induced G 1 arrest and differentiation activation, which provide new insights to explore the inversely coordinated P/D transition at G 1 exit.The cyclin-dependent kinase (CDK) 1 -activating kinase (CAK), a trimeric CDK7-cyclin H-MAT1 (ménage à trois 1) complex, was originally implicated in cell cycle control by its ability to phosphorylate and activate CDKs (1, 2). Previous studies demonstrated that CAK regulates cell cycle G 1 exit both by phosphorylation activation of cyclin D-CDK complexes (3-7) and by phosphorylation inactivation of retinoblastoma tumor suppressor protein (pRb) (8). Also, CAK is a subcomplex of transcription factor IIH (TFIIH) (9 -12) and a kinase of TFIIH that phosphorylates the COOH-terminal domain of the largest subunit of RNA polymerase II for transcription initiation (9, 13-15). Thus, CAK is considered a cross-road regulator in linking cell cycle control with transcription. Recently, distinct regions of MAT1 have been shown to regulate CAK kinase and TFIIH transcription activities (16). To date, comprehensive studies demonstrate that MAT1 regulates CAK substrate specificity and protein-protein interactions, i.e. MAT1 mediates the association of CAK with core TFIIH and shifts CAK substrate preference from CDK2 to the COOH-terminal domain (12,14,17,18). Mice lacking MAT1 are unable to enter S phase and are defective in RNA polymerase II phosphorylation (19). Antisense abrogation of MAT1 induces cell cycle G 1 arrest (20); and MAT1 regulates the interaction and phosphorylation of CAK with tumor suppressor p53 (21), octamer transcription factors (22), pRb (8), and retinoic acid receptor ␣ (RAR␣) (23).Among the above substrates of CAK, RAR␣ is involved mainly in differentiation regulation. RAR␣ belongs to the superfamily of...