Interface carrier recombination currently hinders the performance of hybrid organic–silicon heterojunction solar cells for high-efficiency low-cost photovoltaics. Here, we introduce an intermediate ...1,1-bis(di-4-tolylamino)phenylcyclohexane (TAPC) layer into hybrid heterojunction solar cells based on silicon nanowires (SiNWs) and conjugate polymer poly(3,4-ethylenedioxy-thiophene):poly(styrenesulfonate) (PEDOT:PSS). The highest power conversion efficiency reaches a record 13.01%, which is largely ascribed to the modified organic surface morphology and suppressed saturation current that boost the open-circuit voltage and fill factor. We show that the insertion of TAPC increases the minority carrier lifetime because of an energy offset at the heterojunction interface. Furthermore, X-ray photoemission spectroscopy reveals that TAPC can effectively block the strong oxidation reaction occurring between PEDOT:PSS and silicon, which improves the device characteristics and assurances for reliability. These learnings point toward future directions for versatile interface engineering techniques for the attainment of highly efficient hybrid photovoltaics.
Intercellular heterogeneity occurs widely under both normal physiological environments and abnormal disease-causing conditions. Several attempts to couple spatiotemporal information to cell states in ...a microenvironment were performed to decipher the cause and effect of heterogeneity. Furthermore, spatiotemporal manipulation can be achieved with the use of photocaged/photoactivatable molecules. Here, we provide a platform to spatiotemporally analyze differential protein expression in neighboring cells by multiple photocaged probes coupled with homemade photomasks. We successfully established intercellular heterogeneity (photoactivable ROS trigger) and mapped the targets (directly ROS-affected cells) and bystanders (surrounding cells), which were further characterized by total proteomic and cysteinomic analysis. Different protein profiles were shown between bystanders and target cells in both total proteome and cysteinome. Our strategy should expand the toolkit of spatiotemporal mapping for elucidating intercellular heterogeneity.
Networks of transcriptional and post-transcriptional regulators are critical for bacterial survival and adaptation to environmental stressors. While transcriptional regulators provide rapid ...activation and/or repression of a wide-network of genes, post-transcriptional regulators, such as small RNAs (sRNAs), are also important to fine-tune gene expression. However, the mechanisms of sRNAs remain poorly understood, especially in less-studied bacteria. Deinococcus radiodurans is a gram-positive bacterium resistant to extreme levels of ionizing radiation (IR). Although multiple unique regulatory systems (e.g., the Radiation and Desiccation Response (RDR)) have been identified in this organism, the role of post-transcriptional regulators has not been characterized within the IR response. In this study, we have characterized an sRNA, PprS (formerly Dsr2), as a post-transcriptional coordinator of IR recovery in D. radiodurans. PprS showed differential expression specifically under IR and knockdown of PprS resulted in reduced survival and growth under IR, suggesting its importance in regulating post-radiation recovery. We determined a number of potential RNA targets involved in several pathways including translation and DNA repair. Specifically, we confirmed that PprS binds within the coding region to stabilize the pprM (DR_0907) transcript, a RDR modulator. Overall, these results are the first to present an additional layer of sRNA-based control in DNA repair pathways associated with bacterial radioresistance.
In order to produce microalgal lipids that can be transformed to biodiesel fuel, effects of concentration of CO₂ aeration on the biomass production and lipid accumulation of Nannochloropsis oculata ...in a semicontinuous culture were investigated in this study. Lipid content of N. oculata cells at different growth phases was also explored. The results showed that the lipid accumulation from logarithmic phase to stationary phase of N. oculata NCTU-3 was significantly increased from 30.8% to 50.4%. In the microalgal cultures aerated with 2%, 5%, 10% and 15% CO₂, the maximal biomass and lipid productivity in the semicontinuous system were 0.480 and 0.142gL⁻¹ d⁻¹ with 2% CO₂ aeration, respectively. Even the N. oculata NCTU-3 cultured in the semicontinuous system aerated with 15% CO₂, the biomass and lipid productivity could reach to 0.372 and 0.084gL⁻¹ d⁻¹, respectively. In the comparison of productive efficiencies, the semicontinuous system was operated with two culture approaches over 12d. The biomass and lipid productivity of N. oculata NCTU-3 were 0.497 and 0.151gL⁻¹ d⁻¹ in one-day replacement (half broth was replaced each day), and were 0.296 and 0.121gL⁻¹ d⁻¹ in three-day replacement (three fifth broth was replaced every 3d), respectively. To optimize the condition for long-term biomass and lipid yield from N. oculata NCTU-3, this microalga was suggested to grow in the semicontinuous system aerated with 2% CO₂ and operated by one-day replacement.
This study uses hyperspectral imaging (HSI) and a deep learning diagnosis model that can identify the stage of esophageal cancer and mark the locations. This model simulates the spectrum data from ...the image using an algorithm developed in this study which is combined with deep learning for the classification and diagnosis of esophageal cancer using a single-shot multibox detector (SSD)-based identification system. Some 155 white-light endoscopic images and 153 narrow-band endoscopic images of esophageal cancer were used to evaluate the prediction model. The algorithm took 19 s to predict the results of 308 test images and the accuracy of the test results of the WLI and NBI esophageal cancer was 88 and 91%, respectively, when using the spectral data. Compared with RGB images, the accuracy of the WLI was 83% and the NBI was 86%. In this study, the accuracy of the WLI and NBI was increased by 5%, confirming that the prediction accuracy of the HSI detection method is significantly improved.
Upregulation of Pin1 was shown to advance the functioning of several oncogenic pathways. It was recently shown that Pin1 is potentially an excellent prognostic marker and can also serve as a novel ...therapeutic target for prostate cancer. However, the molecular mechanism of Pin1 overexpression in prostate cancer is still unclear. In the present study, we showed that the mRNA expression levels of Pin1 were not correlated with Pin1 protein levels in prostate cell lines which indicated that Pin1 may be regulated at the post-transcriptional level. A key player in post-transcriptional regulation is represented by microRNAs (miRNAs) that negatively regulate expressions of protein-coding genes at the post-transcriptional level. A bioinformatics analysis revealed that miR-296-5p has a conserved binding site in the Pin1 3′-untranslated region (UTR). A luciferase reporter assay demonstrated that the seed region of miR-296-5p directly interacts with the 3′-UTR of Pin1 mRNA. Moreover, miR-296-5p expression was found to be inversely correlated with Pin1 expression in prostate cancer cell lines and prostate cancer tissues. Furthermore, restoration of miR-296-5p or the knockdown of Pin1 had the same effect on the inhibition of the ability of cell proliferation and anchorage-independent growth of prostate cancer cell lines. Our results support miR-296-5p playing a tumor-suppressive role by targeting Pin1 and implicate potential effects of miR-296-5p on the prognosis and clinical application to prostate cancer therapy.
•We identified that miR-296-5p is a Pin1 regulatory miRNA in prostate cancer.•Specific 3′-untranslated region of Pin1 mRNA is the direct target of miR-296-5p.•Expression of miR-296-5p and Pin1 was inversely correlated in prostate cancer.•MiR-296-5p playing a tumor-suppressive role by targeting Pin1•Targeting miR-296-5p/Pin1 interaction is new avenue for prostate cancer treatment.
Abstract During the course of oncogenesis and tumor progression, cancer cells constitutively upregulate signaling pathways relevant to cell proliferation and survival as a strategy to overcome ...genomic instability and acquire resistance phenotype to chemotherapeutic agents. In light of this clinical and molecular heterogeneity of human cancers, it is desirable to concomitantly target these genetic abnormalities by using an agent with pleiotropic mode of action. Indole-3-carbinol and its metabolite 3,3′-diindoylmethane (DIM) target multiple aspects of cancer cell-cycle regulation and survival including Akt-NFκB signaling, caspase activation, cyclin-dependent kinase activities, estrogen metabolism, estrogen receptor signaling, endoplasmic reticulum stress, and BRCA gene expression. This broad spectrum of anti-tumor activities in conjunction with low toxicity underscores the translational value of indole-3-carbinol and its metabolites in cancer prevention/therapy. Furthermore, novel anti-tumor agents with overlapping underlying mechanisms have emerged via structural optimization of indole-3-carbinol and DIM, which may provide considerable therapeutic advantages over the parental compounds with respect to chemical stability and anti-tumor potency. Together, these agents might foster new strategies for cancer prevention and therapy.
Small noncoding RNAs (sRNAs) are posttranscriptional regulators that have been identified in multiple species and shown to play essential roles in responsive mechanisms to environmental stresses. The ...natural ability of specific bacteria to resist high levels of radiation has been of high interest to mechanistic studies of DNA repair and biomolecular protection. Deinococcus radiodurans is a model extremophile for radiation studies that can survive doses of ionizing radiation of >12,000 Gy, 3,000 times higher than for most vertebrates. Few studies have investigated posttranscriptional regulatory mechanisms of this organism that could be relevant in its general gene regulatory patterns. In this study, we identified 199 potential sRNA candidates in D. radiodurans by whole-transcriptome deep sequencing analysis and confirmed the expression of 41 sRNAs by Northern blotting and reverse transcriptase PCR (RT-PCR). A total of 8 confirmed sRNAs showed differential expression during recovery after acute ionizing radiation (15 kGy). We have also found and confirmed 7 sRNAs in Deinococcus geothermalis, a closely related radioresistant species. The identification of several novel sRNAs in Deinococcus bacteria raises important questions about the evolution and nature of global gene regulation in radioresistance.
: Cancer cells reprogram cellular metabolism to fulfill their needs for rapid growth and metastasis. However, the mechanism controlling this reprogramming is poorly understood. We searched for ...upregulated signaling in metastatic colorectal cancer and investigated the mechanism by which Glut3 promotes tumor metastasis.
: We compared RNA levels and glycolytic capacity in primary and metastatic colon cancer. The expression and association of Glut3 with clinical prognosis in colon cancer tissues was determined by immunohistochemistry. Glut3 gain-of-function and loss-of-function were established using colon cancer HCT116, HT29, and metastatic 116-LM cells, and tumor invasiveness and stemness properties were evaluated. Metabolomic profiles were analyzed by GC/MS and CE-TOF/MS. The metastatic burden in mice fed a high-fat sucrose diet was assessed by intravenous inoculation with Glut3 knockdown 116-LM cells.
: Upregulation of glycolytic genes and glycolytic capacity was detected in metastatic colorectal cancer cells. Specifically, Glut3 overexpression was associated with metastasis and poor survival in colorectal cancer patients. Mechanistically, Glut3 promoted invasiveness and stemness in a Yes-associated protein (YAP)-dependent manner. Activation of YAP in turn transactivated Glut3 and regulated a group of glycolytic genes. Interestingly, the expression and phosphorylation of PKM2 were concomitantly upregulated in metastatic colorectal cancer, and it was found to interact with YAP and enhance the expression of Glut3. Importantly, a high-fat high-sucrose diet promoted tumor metastasis, whereas the inhibition of either Glut3 or YAP effectively reduced the metastatic burden.
: Activation of the Glut3-YAP signaling pathway acts as a master activator to reprogram cancer metabolism and thereby promotes metastasis. Our findings reveal the importance of metabolic reprogramming in supporting cancer metastasis as well as possible therapeutic targets.
Background Chemoradiotherapy (CRT), which might affect the autonomic system, is the mainstay therapy for advanced esophageal squamous cell carcinoma (ESCC). Autonomic dysfunction has been found to ...possibly lead to cancer mortality in those with elevated resting heart rates (RHR). Skin sympathetic nerve activity (SKNA) is a new method of stimulating electrical signals in skin to evaluate autonomic function from sympathetic tone. In this study, we investigated the association between changes in RHR and autonomic function and ESCC mortality. Methods Thirty-nine stage II-IV ESCC patients receiving CRT between March 2019 and November 2020 were prospectively enrolled and carefully selected, followed up and received the same meticulous supportive care. Serial RHR was recorded every two weeks from before CRT to eight weeks after CRT and average SKNA were recorded before and four weeks after CRT. All-cause mortality was defined as primary outcome. Results We found the RHR of ESCC patients to be significantly elevated and peaking at four weeks after CRT (p < 0.001) and then to gradually decrease. Those with an elevated RHR above the cutoff level (18 beat-per-minute) at eight weeks after CRT had worse overall survival. In addition, those with higher baseline sympathetic tone (average SKNA greater than or equal to 0.86 muV) also had poor outcome. Conclusions Increased pre-treatment sympathetic tone and elevated RHR after CRT are alarm signs of poor ESCC outcome. Further exploration of the mechanisms underlying these associations could potentially lead to intervention strategies for reducing mortality. Trial registration This study is registered with ClinicalTrials.gov, identifier: NCT03243448. Keywords: Esophageal squamous cell carcinoma, Chemoradiotherapy, Resting heart rate, Skin sympathetic nerve activity, Autonomic nerve system, Survival
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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