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Mulched drip irrigation is a highly effective water-saving technique that is commonly employed in arid regions. However, the residual plastic film left behind in the soil poses a significant challenge to the sustainable growth of agriculture. To address this issue, sprayable degradable film, which is both biodegradable and non-polluting, represents a superior alternative to the traditional plastic film. This study aimed to investigate the relationship between cotton growth and development, physiological characteristics, yield, and water use efficiency under varying dosages of sprayable degradable film. The goal was to mitigate the hazards of residual film. A field experiment was conducted in Xinjiang, Northwest China to test the effects of five different mulching conditions: SF1 (1900 kg of sprayable degradable film per ha), SF2 (2200 kg of sprayable degradable film per ha), SF3 (2500 kg of sprayable degradable film per ha), PF (plastic film), and NF (no film mulching). Results showed that mulching with the sprayable degradable film had a positive impact on the soil hydrothermal environment, promoted root growth, significantly increased plant height and leaf area, and enhanced physiological characteristics compared to the no film mulching treatment, which ultimately improved yield and water use efficiency. The study found that cotton root length density, root weight density, and net photosynthesis showed significant linear relationships with yield. Compared to the NF, the yield of sprayable degradable film treatments increased by 11.79%, 14.39%, and 15.00%, and the water use efficiency increased by 21.88%, 23.96%, and 30.21%, respectively. The maximum yield and water use efficiency were observed in PF treatment, with 5345 kg ha-1 and 1.28 kg m-3, respectively. The yield and water use efficiency of SF3 was close to PF. In general, applying moderate amounts of sprayable degradable film at a rate of 2500 kg ha-1 can significantly boost cotton growth, improve photosynthetic characteristics, and increase cotton yield and water use efficiency. This study presents an effective agronomic strategy for managing residual film contamination while maintaining stable cotton yield.

The identification of prostate stem/progenitor cells and characterization of the prostate epithelial cell lineage hierarchy are critical for understanding prostate cancer initiation. Here, we characterized 35,129 cells from mouse prostates, and identified a unique luminal cell type (termed type C luminal cell (Luminal-C)) marked by Tacstd2, Ck4 and Psca expression. Luminal-C cells located at the distal prostate invagination tips (termed Dist-Luminal-C) exhibited greater capacity for organoid formation in vitro and prostate epithelial duct regeneration in vivo. Lineage tracing of Luminal-C cells indicated that Dist-Luminal-C cells reconstituted distal prostate luminal lineages through self-renewal and differentiation. Deletion of Pten in Dist-Luminal-C cells resulted in prostatic intraepithelial neoplasia. We further characterized 11,374 human prostate cells and confirmed the existence of h-Luminal-C cells. Our study provides insights into the prostate lineage hierarchy, identifies Dist-Luminal-C cells as the luminal progenitor cell population in invagination tips and suggests one of the potential cellular origins of prostate cancer.

For centuries, attempts have been continuously made to artificially reconstitute counterparts of in vivo organs from their tissues or cells. Only in the recent decade has organoid technology as a whole technological field systematically emerged and been shown to play important roles in tissue engineering. Based on their self-organizing capacities, stem cells of versatile organs, both harvested and induced, can form 3D structures that are structurally and functionally similar to their in vivo counterparts. These organoid models provide a powerful platform for elucidating the development mechanisms, modeling diseases, and screening drug candidates. In this review, we will summarize the advances of this technology for generating various organoids of tissues from the three germ layers and discuss their drawbacks and prospects for tissue engineering.

Prostate cancer adeno-to-neuroendocrine lineage transition has emerged as a mechanism of targeted therapeutic resistance. Identifying the direct molecular drivers and developing pharmacological strategies using clinical-grade inhibitors to overcome lineage transition-induced therapeutic resistance are imperative. Here, using single-cell multiomics analyses, we investigate the dynamics of cellular heterogeneity, transcriptome regulation, and microenvironmental factors in 107,201 cells from genetically engineered mouse prostate cancer samples with complete time series of tumor evolution seen in patients. We identify that FOXA2 orchestrates prostate cancer adeno-to-neuroendocrine lineage transition and that Foxa2 expression is significantly induced by androgen deprivation. Moreover, Foxa2 knockdown induces the reversal of adeno-to-neuroendocrine transition. The KIT pathway is directly regulated by FOXA2 and specifically activated in neuroendocrine prostate cancer (NEPC). Pharmacologic inhibition of KIT pathway significantly suppresses mouse and human NEPC tumor growth. These findings reveal that FOXA2 drives adeno-to-neuroendocrine lineage plasticity in prostate cancer and provides a potential pharmacological strategy for castration-resistant NEPC.

This post hoc analysis examines the relationship between glycemic variability (GV) and fasting plasma glucose (FPG) targets used to achieve glycated hemoglobin (HbA1c) 7%, and HbA1c levels after 24 weeks of treatment with insulin glargine and oral antidiabetic drugs (OADs) in Chinese participants with type 2 diabetes mellitus (T2DM) from the BEYOND III FPG GOAL trial (NCT02545842).Participants were randomized for three FBG targets (≤ 5.6 mmol/L, ≤ 6.1 mmol/L, and ≤ 7.0 mmol/L) receiving insulin glargine 100 U/mL were analyzed for mean change from baseline to 24 weeks in postprandial glucose (PPG) excursion and FPG coefficient of variation (FPG-CV). The study analyzed change from baseline in HbA1c and the proportion of participants who achieved HbA1c 7% at 24 weeks, according to their baseline FPG-CV and change from baseline in PPG excursion.The change in PPG excursion and FPG-CV from baseline to 24 weeks was not significantly different between the three groups stratified by randomization or by 24-week FPG levels. While the change in HbA1c from baseline to 24 weeks was slightly higher among participants with baseline FPG-CV 33.3% (vs. 66.7%; P = 0.023), a higher proportion of participants with baseline FPG-CV 33.3% achieved HbA1c 7% (P = 0.021).GV was not associated with either target FPG levels or HbA1c 7.0% after 24 weeks of treatment with insulin glargine and OADs.Clinicaltrials.gov identifier NCT02545842.

Chromatin accessibility plays an essential role in controlling cellular identity and the therapeutic response of human cancers. However, the chromatin accessibility landscape and gene regulatory network of pancreatic cancer are largely uncharacterized. Here, we integrate the chromatin accessibility profiles of 84 pancreatic cancer organoid lines with whole-genome sequencing data, transcriptomic sequencing data and the results of drug sensitivity analysis of 283 epigenetic-related chemicals and 5 chemotherapeutic drugs. We identify distinct transcription factors that distinguish molecular subtypes of pancreatic cancer, predict numerous chromatin accessibility peaks associated with gene regulatory networks, discover regulatory noncoding mutations with potential as cancer drivers, and reveal the chromatin accessibility signatures associated with drug sensitivity. These results not only provide the chromatin accessibility atlas of pancreatic cancer but also suggest a systematic approach to comprehensively understand the gene regulatory network of pancreatic cancer in order to advance diagnosis and potential personalized medicine applications.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a global public health threat. The efficacy of several repurposed drugs has been evaluated in clinical trials. Among these drugs, a second-generation antiandrogen agent, enzalutamide, was proposed because it reduces the expression of transmembrane serine protease 2 (TMPRSS2), a key component mediating SARS-CoV-2-driven entry, in prostate cancer cells. However, definitive evidence for the therapeutic efficacy of enzalutamide in COVID-19 is lacking. Here, we evaluated the antiviral efficacy of enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and Ad-ACE2-transduced mice. Tmprss2 knockout significantly inhibited SARS-CoV-2 infection in vivo. Enzalutamide effectively inhibited SARS-CoV-2 infection in human prostate cells, however, such antiviral efficacy was lacking in human lung cells and organoids. Accordingly, enzalutamide showed no antiviral activity due to the AR-independent TMPRSS2 expression in mouse and human lung epithelial cells. Moreover, we observed distinct AR binding patterns between prostate cells and lung cells and a lack of direct binding of AR to TMPRSS2 regulatory locus in human lung cells. Thus, our findings do not support the postulated protective role of enzalutamide in treating COVID-19 through reducing TMPRSS2 expression in lung cells., Enzalutamide, an approved drug for prostate cancer, acts on TMPRSS2 expression, a key mediator for SARS-CoV-2 infection. Here, the authors characterize the anti-SARS-CoV-2 effects of Enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and in hACE2-transduced Tmprss2 knockout mice and show lack antiviral action in human lung cells and human lung organoids, likely due to the AR-independent TMPRSS2 expression in mouse and human lung epithelial cells.

Although cancer is commonly perceived as a disease of dedifferentiation, the hallmark of early-stage prostate cancer is paradoxically the loss of more plastic basal cells and the abnormal proliferation of more differentiated secretory luminal cells. However, the mechanism of prostate cancer proluminal differentiation is largely unknown. Through integrating analysis of the transcription factors (TFs) from 806 human prostate cancers, we found that ERG was highly correlated with prostate cancer luminal subtyping. ERG overexpression in luminal epithelial cells inhibited those cells' normal plasticity to transdifferentiate into a basal lineage, and ERG superseded PTEN loss, which favored basal differentiation. ERG KO disrupted prostate cell luminal differentiation, whereas AR KO had no such effects. Trp63 is a known master regulator of the prostate basal lineage. Through analysis of 3D chromatin architecture, we found that ERG bound and inhibited the enhancer activity and chromatin looping of a Trp63 distal enhancer, thereby silencing its gene expression. Specific deletion of the distal ERG binding site resulted in the loss of ERG-mediated inhibition of basal differentiation. Thus, ERG, in its fundamental role in lineage differentiation in prostate cancer initiation, orchestrated chromatin interactions and regulated prostate cell lineage toward a proluminal program.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a global public health threat due to the lack of effective drugs or vaccines against SARS-CoV-2. The efficacy of several repurposed drugs has been evaluated in clinical trials. Among these drugs, a relatively new antiandrogen agent, enzalutamide, was proposed because it reduces the expression of transmembrane serine protease 2 (TMPRSS2), a key component mediating SARS-CoV-2-driven entry into host cells, in prostate cancer cells. However, definitive evidence for the therapeutic efficacy of enzalutamide in COVID-19 is lacking. Here, we evaluated the antiviral efficacy of enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and SARS-CoV-2-infected Ad-ACE2-transduced Tmprss2 knockout (Tmprss2-KO) and wild-type (WT) mice. TMPRSS2 knockout significantly inhibited SARS-CoV-2 infection in vivo. Enzalutamide effectively inhibited SARS-CoV-2 infection in human prostate cancer cells (LNCaP) but not in human lung cancer cells or patient-derived lung organoids. Although Tmprss2 knockout effectively blocked SARS-CoV-2 infection in ACE2-transduced mice, enzalutamide showed no antiviral activity due to the AR independence of TMPRSS2 expression in mouse and human lung epithelial cells. Moreover, we observed distinct AR binding patterns between prostate cells and lung cells and a lack of direct binding of AR to TMPRSS2 in human lung cells. Thus, our findings do not support the postulated protective role of enzalutamide in treating COVID-19.

FPG GOAL was a 24-week, open-label, treat-to-target randomized controlled trial which demonstrated that the optimal self-monitored fasting blood glucose (SM-FBG) target for most Chinese individuals with type 2 diabetes (T2D) using insulin glargine 100 IU/mL was 3.9-6.1 mmol/L. Individuals who achieved lower fasting plasma glucose (FPG) levels might achieve the target HbA1c of 7% without increasing the risk of hypoglycemia.For this post hoc analysis, individuals were redivided into three groups based on their actual laboratory FPG levels at 24 weeks: level 1, ≤ 5.6 mmol/L; level 2, 5.6 to ≤ 6.1 mmol/L; and level 3, 6.1 to ≤ 7.0 mmol/L.At week 24, 863 individuals with diabetes had available FPG data and 179, 122, and 179 individuals achieved FPG levels 1, 2, and 3, respectively. The proportion of individuals with HbA1c 7% or HbA1c 7% without hypoglycemia (≤ 3.9 or ≤ 3.0 mmol/L) was significantly higher in FPG levels 1 (p 0.01) and 2 (p 0.05) than in level 3. The least squares mean changes from baseline in HbA1c (- 1.77% and - 1.66% vs - 1.34%; both p 0.001) and 2-h postprandial glucose (- 3.88 mmol/L and - 3.98 mmol/L vs - 3.22 mmol/L; both p 0.05) were also significantly higher in FPG levels 1 and 2 compared with level 3. Linear regression analysis showed a moderate relationship between FPG and HbA1c levels at 24 weeks (r = 0.449).Chinese individuals with T2D who achieved lower FPG levels with insulin glargine 100 IU/mL were more likely to achieve the recommended target HbA1c of 7% compared with those with higher FPG levels. ClinicalTrials.gov identifier NCT02545842.

While cancer is commonly perceived as a disease of dedifferentiation, the hallmark of early stage prostate cancer is paradoxically the loss of more plastic basal cells and the abnormal proliferation of more differentiated secretory luminal cells. However, the mechanism of prostate cancer pro-luminal differentiation is largely unknown. Through integrating analysis of the transcription factors (TFs) from 806 human prostate cancers, we have identified that ERG highly correlated with prostate cancer luminal subtyping. ERG overexpression in luminal epithelial cells inhibits its normal plasticity to transdifferentiate into basal lineage and ERG supersedes PTEN-loss which favors basal differentiation. ERG knock-out disrupted prostate cell luminal differentiation, whereas AR knock-out had no such effects. Trp63 is a known master regulator of prostate basal lineage. Through analysis of 3D chromatin architecture, we found that ERG binds and inhibits the enhancer activity and chromatin looping of a Trp63 distal enhancer, thereby silencing its gene expression. Specific deletion of the distal ERG binding site resulted in the loss of ERG-mediated inhibition of basal differentiation. Thus, ERG orchestrates chromatin interactions and regulates prostate cell lineage toward pro-luminal program, as its fundamental role on lineage differentiation in prostate cancer initiation.

IntroductionThis study investigated miR-29b-3p’s effects and mechanisms in preeclampsia development.Material and methodsIn this study, we analysed the pathology and expression of miR-29b-3p and B2R mRNA from normal and preeclampsia placenta tissues using hematoxylin and eosin staining and RT-qPCR assay. For cell experiments, we used transwell assay CCK-8, flow cytometry and wound healing assay to determine the effects and correlation of miR-29b-3p and B2R in HTR-8/SVneo cell proliferation, apoptosis, cell cycle, cell invasion and migration in a preeclampsia cell model. Moreover, the mechanisms were determined using Western blot or immunofluorescence in different groups.ResultsClinical analysis revealed that miR-29b-3p gene expression dramatically increased with increasing degree of preeclampsia (p < 0.001 or p < 0.05, respectively). The HTR-8/SVneo cell biological activities of the model group were significantly depressed (p < 0.001). However, with miR-29b-3p inhibitor or B2R transfection, the HTR-8/SVneo cell biological activities significantly recovered (p < 0.001). Western blot assay showed that B2R, VEGF-A, CCND-1, MMP-2 and MMP-9 levels were suppressed in the model group, compared with those in the NC groups (p < 0.001, respectively). With miR-29b-3p inhibitor or B2R transfection, the protein expression levels of B2R, VEGF-A, CCND-1, MMP-2 and MMP-9 dramatically increased (p < 0.001, respectively).ConclusionsThe down-regulation of miR-29b-3p could improve HTR-8/SVneo cell biological activities in a preeclampsia cell model by targeting B2R.

The Density Function Theory with van der Waals correction are employed to investigate the materials of CH3NH3PbI3 (MAPbI3). For the two phases of tetragonal and orthorhombic, the high optical absorption coefficients (OAC) result from electrons jumping from I 5p to the Pb 6p near the Fermi level. The two different kinds of iodine vacancy result in the doping energy band appearing in the band gap, and the doping energy band is from Pb 6p electrons mainly, which is below the Fermi level. The iodine vacancy result in the red shift of OAC, which result in the optical absorption of MAPbI3 with the iodine vacancy locating in the range from 0.5 eV to 1.47 eV, which locate at the infrared ray part occupying 51% of radiant energy of sunlight. And the red shift favors power transfer between sunlight and electric. The red shift of the OAC originate electrons jumping from Pb 6p (doping energy bands) to Pb 6p (conduction bands).

// Rui Wang 1 , Yunguang Li 1 , Enze Hu 1 , Fei Kong 1 , Junhao Wang 1 , Jin Liu 1 , Qirui Shao 1 , Ying Hao 2 , Dacheng He 1 , Xueyuan Xiao 1 1 Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, College of Life Science, Beijing Normal University, Beijing, China 2 The Department of Basic Theory, College of Sports, Northwest Normal University, Lanzhou, China Correspondence to: Xueyuan Xiao, email: xyxiao@bnu.edu.cn Keywords: S100A7, lung cancer cells, ADC to SCC transdifferentiation, YAP, the Hippo pathway Received: October 19, 2016 Accepted: January 09, 2017 Published: February 03, 2017 ABSTRACT Our previous study revealed that S100A7 was selectively expressed in lung squamous cell carcinoma tissues but not in adenocarcinoma. Thus far, the functions of S100A7 in lung cancer have remained largely unknown. Here, we reveal that S100A7 overexpression facilitates the transdifferentiation from adenocarcinoma (ADC) to squamous carcinoma (SCC) in several lung cancer cells, which is confirmed by an increase in DNp63 expression and a decrease in thyroid transcription factor 1 (TTF1) and aspartic proteinase napsin (napsin A) expression. Further study finds that activation of the Hippo pathway induces S100A7 expression and further confirms that nuclear YAP acts as a repressor of S100A7 in H292 cells. Subsequently, we verify that TEAD1 is required for YAP transcriptional repression of S100A7. More importantly, we determine that S100A7 overexpression partially rescues lung ADC to SCC transdifferentiation inhibited by YAP overexpression in all tested cells, suggesting that S100A7 and YAP have the opposite effects on lung ADC to SCC conversion. Taken together, our study demonstrates for the first time that S100A7 not only functions as a facilitator of adenous-squamous carcinoma phenotypic transition in lung cancer cells but also that its expression is differentially regulated by the Hippo-YAP pathway.

Objectives: To estimate the direct medical costs (DMCs) and healthcare resource utilization (HRU) of type 2 diabetes mellitus (T2DM)-related complications in China. Methods: Data from a total of 74,507 patients were extracted from the 2015 China Health Insurance Research Association Claims Database. The complications determined by primary diagnoses were categorized into three groups: 1) for mild acute and local chronic complications, both outpatients and inpatients were considered; 2) for severe acute complications, only inpatiens were considered; 3) for systemic chronic complications, a 1:1 propensity-score matching was performed to calculate the incremental DMCs and HRU of preexisting and new-onset patients. Results: Among the mild acute and local chronic complications, the DMCs and HRU per event were the highest for gangrene and laser treatment. Of the severe acute complications, the DMCs and HRU per event were highest for hyperosmotic nonketonic diabetic coma (HNDC), followed by severe hypoglycemia and ketosis. For systemic chronic complications, the DMCs and HRU associated with dialysis and myocardial infarction were the highest both in patients with new-onset complications and preexisting complications. Conclusions: The estimated economic data are required for policy decisions to optimize resource allocation and to evaluate different approaches for disease management.

Background: The optimal fasting glucose target to achieve an HbA1c Methods: This open-label RCT conducted in China (ClinicalTrials.gov, NCT02545842), randomly assigned (1:3:3) adults (aged 18-65 years) with uncontrolled T2D (HbA1c >7% to ≤10.5%) on 1-3 OADs to 1 of 3 self-monitored fasting blood glucose (FBG) target groups: ≤5.6 mmol/L (Group 1), ≤6.1 mmol/L (Group 2), or ≤7.0 mmol/L (Group 3). The lowest of 3 consecutive FBG values was used for insulin glargine 100 U/ml titration decisions. Primary endpoint was the proportion of patients achieving an HbA1c Results: Of 947 patients randomized (Group 1, n=136; Group 2, n=405; Group 3, n=406), 914 were analyzed (mean age 53.9 years; 56.2% male; mean HbA1c 8.59%), and 885 (93.4%) completed the study. At 24 weeks, 44.4%, 46.1%, and 37.7% of patients achieved an HbA1c Conclusions: The optimal FBG target for the majority of patients with T2D appears to be ≤6.1 mmol/L. However, for patients at lower risk of hypoglycemia, an FBG target of ≤5.6 mmol/L may be appropriate. Disclosure W. Yang: Speaker's Bureau; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi, Servier. J. Ma: None. G. Yuan: None. L. Li: None. M. Zhang: None. Y. Lu: None. X. Ye: Speaker's Bureau; Self; AstraZeneca, Merck Sharp & Dohme Corp., Novo Nordisk Inc. W. Song: None. M. Liu: None. J. Wu: None. R. Chen: None. N. Cui: Employee; Self; Sanofi. Y. Li: Employee; Self; Sanofi. X. Zhang: None. J. Yang: None.

Figure S1. The Expression of S100A8 and S100A9 in HCC94 cells. Figure S2. Induction of S100A8 and S100A9 expression in A431 cells. Figure S3. Silencing effect of siRNAs in A431 cells. Figure S4. The expression of YAP and pYAP-S127 in xenografts. Figure S5. S100A8/A9 inhibit cell apoptosis induced by dense culture. Figure S6. YAP and p73 promote cell apoptosis induced by dense culture. Figure S7. Diagram to summarize S100A8 and S100A9 induction procedure. Figure S8. Diagram to summarize S100A8 and S100A9 induction procedure. (a) In normal adherent cultured cells, the Hippo pathway is in a closed state. YAP binding with TEAD in the nucleus, play a role in promoting cell proliferation and inhibiting of cell differentiation. YAP downstream protein ‘X’ binds to the promoter of S100A8 and S100A9, inhibiting S100A8 and S100A9 expression. (b) When SCC cells are detached or cultured in high density, the Hippo pathway are activated and nuclear YAP are decreased so that S100A8 and S100A9 lost the inhibitory effect on protein ‘X’, which leads to them induction. (DOCX 3844 kb)

Methods. Table S1. siRNA sequences. Table S2. Primers used for qPCR. Table S3 S100A8 and S100A9 expression in SCC tissues. (DOCX 25 kb)

// Yunguang Li 1, * , Fei Kong 1, * , Junhao Wang, 1 Enze Hu, 1 Rui Wang, 1 Jin Liu, 1 Qianqian Xiao, 1 Weiqing Zhang, 1 Dacheng He, 1 Xueyuan Xiao 1 1 Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China * These authors contributed equally to this work Correspondence to: Xueyuan Xiao, email: xyxiao@bnu.edu.cn Keywords: S100A7, YAP, Hippo pathway, F-actin, A431 Received: March 10, 2016 Accepted: April 27, 2016 Published: May 19, 2016 ABSTRACT YAP is an oncogenic transcriptional co-activator and is inhibited by the Hippo pathway. Recent studies have revealed that YAP is also a sensor of cell morphology and cell density and can be phosphorylated by cytoskeleton reorganization. Our previous study demonstrated that S100A7 was upregulated in several squamous cell carcinoma (SCC) specimens and was dramatically induced in SCC cells by suspension and dense culture as well as in xenografts. However, little is known about how S100A7 induction occurs in cancer cells. Here, we identify that S100A7 induction is accompanied by YAP phosphorylation in both suspended and dense A431 cells. This correlation reverses after recovery of cell attachment or relief from dense culture. Further examination finds that S100A7 induction is repressed by nuclear YAP, which is further validated by activation or inhibition of the Hippo pathway via loss- and/or gain-of- LATS1 and MST1 function. Strikingly, disruption of the F-actin promotes S100A7 expression via YAP by activation of the Hippo pathway. Furthermore, we demonstrate that repression of S100A7 by YAP required TEAD1 transcriptional factor. Taken together, our findings demonstrate for the first time that S100A7 is repressed by YAP via the Hippo pathway.

// Qianqian Xiao 1, * , Zunlei Qian 1, 2, * , Weiqing Zhang 1 , Jin Liu 1 , Enze Hu 1 , Jinsan Zhang 3 , Mingying Li 1, 4 , Junhao Wang 1 , Fei Kong 1 , Yunguang Li 1 , Rui Wang 1 , Xiaohua Tan 3 , Dacheng He 1 , Xueyuan Xiao 1 1 Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China 2 College of Forensic Sciences, People’s Public Security University of China, Beijing, China 3 School of Pharmaceutical Sciences and Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, China 4 Center of Reproduction and Genetics, First People’s Hospital of Yunnan Province, Kunming, China * These authors contributed equally to this work Correspondence to: Xueyuan Xiao, e-mail: xyxiao@bnu.edu.cn , dhe@bnu.edu.cn Keywords: CABYR-a/b, lung cancer cells, DR5, TRAIL, YAP Received: August 18, 2015 Accepted: January 13, 2016 Published: January 29, 2016 ABSTRACT Our previous study revealed that knockdown of CABYR-a/b increases the chemosensitivity of lung cancer cells through inactivation of Akt. Here, we demonstrated that depletion of CABYR-a/b significantly increased DR5 expression and sensitized lung cancer cells to TRAIL-induced apoptosis in vitro and/or in vivo . Importantly, treatment with AD5-10, a DR5-specific agonistic monoclonal antibody, was able to mimic TRAIL-induced apoptosis in CABYR-a/b-silenced cells. Strikingly, we identified that depletion of CABYR-a/b not only increased the expressions of p73 and DR5 but also decreased the phosphorylation of YAP S127. Loss- or gain-of-function studies of YAP and p73 revealed that double deletions of YAP and p73 effectively decreased the expression of DR5 and abolished TRAIL-induced apoptosis in CABYR-a/b knockdown cells. Conversely, the co-overexpression of YAP and p73 promoted the expression of DR5 and sensitized cells to TRAIL-induced apoptosis. Taken together, our results demonstrate that depletion of CABYR-a/b sensitizes lung cancer cells to TRAIL-induced apoptosis through YAP/p73-mediated DR5 upregulation.

Background S100A8 and S100A9, two heterodimer-forming members of the S100 family, aberrantly express in a variety of cancer types. However, little is known about the mechanism that regulates S100A8/S100A9 co-expression in cancer cells. Methods The expression level of S100A8/S100A9 measured in three squamous cell carcinomas (SCC) cell lines and their corresponding xenografts, as well as in 257 SCC tissues. The correlation between S100A8/S100A9, Hippo pathway and F-actin cytoskeleton were evaluated using western blot, qPCR, ChIP and Immunofluorescence staining tests. IncuCyte ZOOM long time live cell image monitoring system, qPCR and Flow Cytometry measured the effects of S100A8/S100A9 and YAP on cell proliferation, cell differentiation and apoptosis. Results Here, we report that through activation of the Hippo pathway, suspension and dense culture significantly induce S100A8/S100A9 co-expression and co-localization in SCC cells. Furthermore, these expressional characteristics of S100A8/S100A9 also observed in the xenografts derived from the corresponding SCC cells. Importantly, Co-expression of S100A8/S100A9 detected in 257 SCC specimens derived from five types of SCC tissues. Activation of the Hippo pathway by overexpression of Lats1, knockdown of YAP, as well as disruption of F-actin indeed obviously results in S100A8/S100A9 co-expression in attached SCC cells. Conversely, inhibition of the Hippo pathway leads to S100A8/S100A9 co-expression in a manner opposite of cell suspension and dense. In addition, we found that TEAD1 is required for YAP-induced S100A8/S100A9-expressions. The functional studies provide evidence that knockdown of S100A8/S100A9 together significantly inhibit cell proliferation but promote squamous differentiation and apoptosis. Conclusions Our findings demonstrate for the first time that the expression of S100A8/S100A9 is inducible by changes of cell shape and density through activation of the Hippo pathway in SCC cells. Induced S100A8/S100A9 promoted cell proliferation, inhibit cell differentiation and apoptosis. Electronic supplementary material The online version of this article (10.1186/s12885-019-5784-0) contains supplementary material, which is available to authorized users.

S100A7 is expressed in many squamous cell carcinomas (SCCs), such as SCC of the skin, and well-differentiated SCC always displays stronger staining of this protein. A431 cells, an epidermal cancer cell line, were selected as a cell model to investigate the roles and mechanism of S100A7 in SCC of the skin. In this study, we demonstrated that the overexpression of S100A7 in A431 cells significantly promoted cell proliferation in vitro and tumor growth in vivo, whereas it suppressed the expression of GATA-3, caspase-14 and three squamous differentiation markers, keratin-1, TG-1 and involucrin. Conversely, the overexpression of caspase-14 not only significantly decreased cell proliferation and delayed tumor growth but also markedly induced the expression of three squamous differentiation markers, whereas S100A7 and GATA-3 were not influenced. Further evidence showed that silencing GATA-3 greatly inhibited the expression of caspase-14 and three differentiation markers, while the expression of S100A7 was not changed; contrary results were obtained when overexpressing GATA-3. Importantly, restoring the expression of GATA-3 and caspase-14 in A431-S100A7 cells could bypass the ability of S100A7 to increase cell viability and repress squamous differentiation. These data suggested that S100A7 expression in SCC may play an important role in the maintenance of SCC cell dedifferentiation, at least in SCC of the skin.

In several squamous cell carcinoma (SCC) cells, it has been previously observed that induction of the S100 calcium-binding protein A7 (S100A7) is repressed by YAP via the Hippo pathway. This report now demonstrates that S100A7 also represses YAP expression and activity by ΔNp63 in cancer cells. Stable overexpression of S100A7 activates the NFκB pathway and inhibits the expression of ΔNp63. Caffeic acid phenethyl ester (CAPE), as a specific inhibitor of NFκB, counteracts the inhibitory effect of S100A7 on the expression of ΔNp63 and its target genes. Depletion of S100A7 significantly promotes ΔNp63 expression. These data indicate that S100A7 acts as a suppressor of ΔNp63. Mechanistic examination finds that ΔNp63 not only directly binds to the region of YAP promoter and induces its expression, but also inhibits the Hippo pathway and enhances YAP activity. Importantly, either the positive correlation between S100A7 and YAP phosphorylation at S127 or the negative correlation between S100A7 and ΔNp63 is also observed in skin SCC tissues. Chemosensitivity analysis reveals that S100A7 enhances cancer cells' resistance by inhibition of YAP expression and activity. These results demonstrate that S100A7 is an upstream modulator of the Hippo pathway and extend our understanding of S100A7 functions in cancer. Implications: S100A7 is a new upstream regulator of the Hippo signaling pathway and reduces chemosensitivity of SCC cells through inhibitions of YAP expression and activity. Mol Cancer Res; 15(12); 1752–63. ©2017 AACR.

Microbial fuel cell (MFC), which can directly generate electricity from biodegradable materials, has been receiving increasing attention. Effects of temperature change on power density, electrode potential, columbic efficiency, chemical oxygen demand removal and internal resistance in two chambers MFCs were examined in this paper. The maximum power density of 7.89 W/m3 was achieved at 37 degrees C, with 199% higher at 10 degrees C (2.64 W/m3), 24% higher at 30 degrees C (6.34 W/m3) and 21% higher at 43 degrees C, no steady power generation was observed at 55 degrees C. Low temperature to 10 degrees C might have a huge effect on anode potential, especially at higher current, but increasing the temperature to 43 degrees C had a main effect on the cathode performance when the MFCs have been established at 37 degrees C. The internal resistance of MFC was about 29 omega at 37 degrees C, and increased 62% and 303% when MFC switched to 30 degrees C and 10 degrees C. Similarly, internal resistance increased 48% at 43 degrees C. The effect of temperature on MFC performance was expressed by internal resistance, the higher the internal resistance of MFC, the lesser the power density obtained. The Columbic efficiencies were 8.65% at 30 degrees C, 8.53% at 37 degrees C, and 13.24% at 43 degrees C. These results demonstrate that MFCs can effectively be operated over a wide range of temperatures.

S100A7 is expressed in many squamous cell carcinomas (SCCs). Our previous study revealed that S100A7 was dramatically induced in several SCC cells and activation of the Hippo pathway significantly promoted S100A7 in epidermoid carcinoma cells. However, whether the Hippo pathway regulates S100A7 expression in SCCs remains largely unknown. Here, we uncover that S100A7 induction by the Hippo-YAP pathway displays different characteristic in cervical and glossopharyngeal SCC. In well differentiated HCC94 cervical cells and FaDu pharyngeal cells, S100A7 is easily induced by both suspension and dense culture, which is accompanied by an increase in YAP phosphorylation and a decrease in nuclear YAP. Strikingly, these correlations of S100A7 and YAP reverse after recovery of cell attachment or relief from dense culture. Further examination finds that S100A7 induction is significantly repressed by nuclear YAP, which is validated by activation or inhibition of the Hippo pathway via loss- and/or gain-of- LATS1 and MST1 function. Subsequently, we prove that TEAD1 is required for YAP transcriptional repression of S100A7. However, S100A7 is hardly induced in poorly differentiated SiHa cervical cells and NCI-H226 pulmonary cells even in suspension or activation of the Hippo pathway. More importantly, cervical and lingual SCC tissues array analyses show that S100A7 expression displays the positive correlation with pYAP-S127 and the negative correlation with nuclear YAP in the majority of well differentiated but not in poorly differentiated tissues. Collectively, our findings demonstrate that the different induction of S100A7 toward activation of the Hippo pathway mainly depends on the degree of cell differentiation in cervical and glossopharyngeal SCC.

A new morphology named as feathery structure was firstly discovered in the reaction zone of system Zn/CuTi2 annealed at 663 K for various times. Using scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDS), it was clarified that the rachis of the feathery structure contains the aggregated phases of TiZn3 and CuZn2, while the barb is really the periodic-layered structure of the two phases. The formation mechanism was ascribed to the serrated co-growth of the periodic-layered structure and the aggregate structure at the reaction front corresponding to the different crystal orientations of substrate CuTi2. Very importantly, the discovery of the feathery structure provided a clear and comprehensive pattern for understanding the morphology evolution of the ternary systems from the simple-layered structure to the complicated feathery structure.

Using Nostoc commune as experiment target, the effect of CO2 with different concentrations in atmosphere and dosage of UV-B on photosynthetic pigment chlorophyll a (Chl a), carotenoids, phycoerythrin, phycocyanin, allophycocyanin and UV-B masking materials was studied. The results showed that high dosage of UV-B radiation inhibited the synthesis process of Chl a, phycoerythrin, phycocyanin and allophycocyanin, but promoted the synthesis of carotenoids, MAAs and scytonemin, thus the negative effect produced by UV-B radiation was reduced and the resistance of Nostoc commune against UV-B radiation was enhanced.

S100A7 is highly expressed in squamous cell carcinomas (SCC) and is related to the terminal differentiation of keratinocytes. However, its characteristic and function in SCC is not very known. In this present study, we used immunohistochemistry to examine the expression of S100A7 in 452 SCC specimens, including the lung, esophagus, oral cavity, skin, cervix, bladder, and three SCC cell lines. We found that S100A7-positive staining showed significant heterogeneity in six types of SCC specimen and three SCC cell lines. Further examination found that S100A7-positive cells and its expression at mRNA and protein levels could be induced in HCC94, FaDu, and A-431 cells both in vitro and in vivo using immunohistochemistry, real-time PCR, and Western blotting. Notably, the upregulation of squamous differentiation markers, including keratin-4, keratin-13, TG-1, and involucrin, also accompanied S100A7 induction, and a similar staining pattern of S100A7 and keratin-13 was found in HCC94 cells both in vitro and in vivo. Further study revealed that the overexpression of S100A7 significantly increased proliferation and inhibited squamous differentiation in A-431 cells both in vitro and in vivo. Conversely, silencing S100A7 inhibited cell growth and survival and increased the expression of keratin-4, keratin-13, TG-1, and involucrin in HCC94 cells. Therefore, these results demonstrate that S100A7 displays heterogeneous and inducible characteristic in SCC and also provide novel evidence that S100A7 acts as a dual regulator in promoting proliferation and suppressing squamous differentiation of SCC.

Microbial contamination is the main cause of loss of biomass yield in microalgal cultures, especially under outdoor environmental conditions. Little is known about the identities of microbial contaminants in outdoor mass algal cultures. In this study, a new genus and species of vampyrellid amoeba, Vernalophrys algivore , is described from cultures of Scenedesmus dimorphus in open raceway ponds and outdoor flat-panel photobioreactors. This vampyrellid amoeba was a significant grazer of Scenedesmus and was frequently associated with a very rapid decline in algal numbers. We report on the morphology, subcellular structure, feeding behavior, molecular phylogeny, and life cycle. The new amoeba resembles Leptophrys in the shape of trophozoites and pseudopodia and in the mechanism of feeding (mainly by engulfment). It possesses two distinctive regions in helix E10_1 (nucleotides 117 to 119, CAA) and E23_1 (nucleotides 522 and 523, AG) of the 18S rRNA gene. It did not form a monophyletic group with Leptophrys in molecular phylogenetic trees. We establish a new genus, Vernalophrys , with the type species Vernalophrys algivore . The occurrence, impact of the amoeba on mass culture of S. dimorphus , and means to reduce vampyrellid amoeba contamination in Scenedesmus cultures are addressed. The information obtained from this study will be useful for developing an early warning system and control measures for preventing or treating this contaminant in microalgal mass cultures.

Applications of computer simulation methods, such as atomistic simulation, coarse-grain simulation and mesoscopic simulation, on surfactant assemblies at the interface, surfactant aggregates, and the surfactant/polymer assemblies were summarized based on our works. And the development and prospect of applying computer simulation to study self-assembling surfactant systems were also referred to.

Algal size can affect the rate of metabolism and of growth. Different sized colonies of Nostoc sphaeroides were used with the aim of determining the effects of colony size on photosynthetic physiology and growth. Small colonies showed higher maximum photosynthetic rates per unit chlorophyll, higher light saturation point, and higher photosynthetic efficiency (α) than large colonies. Furthermore, small colonies had a higher affinity for DIC and higher DIC-saturated photosynthetic rates. In addition, small colonies showed higher photosynthetic rates from 5 – 45°C than large colonies. There was a greater decrease in Fv/Fm after exposure to high irradiance and less recovery in darkness for large colonies than for small colonies. Relative growth rate decreased with increasing colony size. Small colonies had less chl a and mass per unit surface area. The results indicate that small colonies can harvest light and acquire DIC more efficiently and have higher maximum photosynthetic rates and growth rates than larg...

Omi/HtrA2 promotes cell apoptosis in human cancer cells. Early studies showed that primary hepatocellular carcinoma requires Omi/HtrA2 expression for cell apoptosis. Additionally, the Omi/HtrA2 pro-apoptotic marker demonstrated a difference in some cell types. However, how the Omi/HtrA2 pro-apoptotic marker reacts during the process of hepatocellular carcinoma cell apoptosis remains to be determined. Thus, we investigated the role and possible mechanism of Omi/HtrA2 on hepatocellular carcinoma cell apoptosis using various hepatocellular carcinoma cell lines. The results were analyzed using RT‑qPCR and western blot analysis. In the present study, we found that Omi/HtrA2 was overexpressed in hepatocellular carcinoma cell lines and induced hepatocellular carcinoma cell apoptosis. Additiionally, the only manner in which Omi/HtrA2 participated in cell death in PLC cells may be dependent on IAP-binding. Omi/HtrA2‑inducing HepG2 cell apoptosis may mainly depend on its serine protease activity while both IAP-binding and its serine protease activity participated in Hep3B cell apoptosis. This result suggested that Omi/HtrA2 pro-apoptotic marker differs in various hepatocellular carcinoma cell lines. PLC cells were also devoid of the expression of ped/pea-15 as the substrate of Omi/HtrA2 serine protease while ped/pea-15 was overexpressed in HepG2 and Hep3B cells and ped/pea-15 expression was higher in HepG2 cells than that in Hep3B cells. These results showed that Omi/HtrA2 overexpression promotes hepatocellular carcinoma cell apoptosis and the ped/pea-15 expression level causes this difference of the Omi/HtrA2 pro-apoptotic marker in the various hepatocellular carcinoma cell lines.

BACKGROUND/AIMS To investigate Omi/HtrA2 expression and its clinical significance in hepatocellular carcinoma. METHODOLOGY We analyzed Omi/HtrA2 expression in hepatocellular carcinoma, paracancerous tissues and normal hepatic tissues by immunohistochemistry, RT-PCR and Western blot. Hypoxia-inducible factor-1α (HIF-1α) expression was also detected in hepatocellular carcinoma samples by immunohistochemistry. Meanwhile, we retrospectively analyzed the relationship between Omi/HtrA2 expression and the survival times of the patients. RESULTS We found that Omi/HtrA2 overexpressed in hepatocellular carcinoma and was correlated with hepatocellular carcinoma differentiation, tumor size, portal vein invasion, clinical stage and lymph node metastasis. We also observed a significant inverse correlation between the expression of Omi,/HtrA2 and HIF-1α in hepatocellular carcinoma. The Kaplan-Meier estimates showed that patients who were Omi/HtrA2 positive had much longer survival times than those who were Omi/HtrA2 negative. Both univariate and multivariate analysis using the Cox regression model indicated that Omi/HtrA2 expression was a significant factor for prognosis. CONCLUSIONS Hepatocellular carcinoma cells may need Omi/HtrA2 expression for apoptosis and Omi/HtrA2 might be an important prognostic marker for primary hepatocellular carcinoma.

Hypoxia-inducible factor-1alpha (HIF-1alpha) plays an important role in regulating hepatoma cell apoptosis. However, conclusions of different studies about the effects of HIF-1alpha expression on hepatoma cell apoptosis remain controversial. Omi/HtrA2 promotes cell apoptosis in some human cancer cells. Our previous experiments have demonstrated that primary hepatocellular carcinoma may need Omi/HtrA2 expression for cell apoptosis. Thus, we investigated the effect of HIF-1alpha on hepatocellular carcinoma cell apoptosis and Omi/ HtrA2 expression. In our study we found that HIF-1alpha gene could suppress hepatoma cell apoptosis, and Omi/HtrA2 mRNA and protein expression decreased with HIF-1alpha expression increase while Bcl-2 mRNA and protein expression increased with HIF-1alpha expression increase in HepG2 cells under normoxia condition. Meanwhile, Omi/HtrA2 protein expression increased with HIF-1alpha expression decrease in HepG2 cells under hypoxia culture. Taken together, these results demonstrated that HIF-1alpha suppressed hepatocellular carcinoma cell apoptosis through inhibiting Omi/HtrA2 expression and upregulating Bcl-2 expression to impede Omi/ HtrA2 releasing from the mitochondrion. The present finding further enriched and supported the role of HIF-1alpha expression on cell apoptosis of hepatoma cells.

Microalgae have the ability to undergo programmatic changes in photosynthetic carbon partitioning and thus cellular biochemical composition, particularly in the relative amounts of crude protein, lipids, and carbohydrate, in response to changes in environmental and culture conditions. In this study, a novel strategy that employs a single microalgal strain Scenedesmus dimorphus grown in a single cultivation platform to produce protein-, carbohydrate- or lipid-rich biomass, as so desired, was introduced. With the combined manipulation of nitrogen availability and light intensity and cell inoculation density, it was successfully demonstrated that highest yields for protein and carbohydrate were 0.2 and 0.7 g L(-1) d(-1), respectively, which could be obtained in early stages of cultivation, while the highest yield for lipid, 0.17 g L(-1) d(-1), occured in a late stage of cultivation.

Hypoxia-inducible-1α (HIF-1α) expression was intimately correlated with apoptosis and proliferation of cancer cells. However, conclusions of different studies on the effects of HIF-1α expression on cell apoptosis and cell proliferation of hepatoma cells remain controversial. In view of the current status, we reassess its roles and possible mechanism in hepatoma cells. In order to acquire more convincing and reliable results, we used a Tet-on system to stably and effectively regulate HIF-1α expression in the HepG2 cells in vitro. In our study we not only confirmed some common conclusions of previous studies, but also acquired some different and significant results that HIF-1α facilitates cell proliferation and cell cycle through influencing the expression of cyclin A and cyclin D, and suppresses cell apoptosis through inducing the expression of survivin and Bcl-2. These results further enrich our knowledge on the role of HIF-1α expression on cell apoptosis and cell proliferation of hepatoma cells.

To investigate the relationship between the expression of cyclooxygenase-2 (COX-2) and menstrual cycle, the regulatory effects of 17-beta-estradiol (E(2)) and medroxyprogesterone acetate (MPA) on the expression of COX-2 in cervical cancer Hela cells were examined. Cervical cancer specimens were obtained from 47 pre-menopausal patients. The phase of menstrual cycle was determined by case history and HE staining of uterine endometrium. COX-2 was immunohistochemically stained by SABC staining and the staining intensity was determined with computerized image analysis system. Hela cells were incubated with alcohol, E(2), E(2)+MPA, MPA for 12, 24 and 48 h respectively. The expression of COX-2 in Hela cells was detected by Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR). Our results showed that the expression of COX-2 was significantly higher during proliferative phase than secretory phase (P0.05), but there was no difference in the positive rate between proliferative phase and secretory phase (P0.05). Incubation with E(2) could significantly enhance the expression of COX-2 continually. On the contrary, E(2)+MPA and MPA alone could decrease the expression of COX-2 as compared with the control and E(2) group (P0.05 and P0.01 respectively). It is concluded that the expression of COX-2 in cervical cancer of pre-menopausal patients and Hela cells was regulated by estrogen/progestogen.