Wee1 inhibitor PD0166285 sensitized TP53 mutant lung squamous cell carcinoma to cisplatin via STAT1.

BACKGROUND: Lung squamous cell carcinoma (LUSCs) is associated with high mortality (20-30%) and lacks of effective treatments. Almost all LUSC exhibit somatic mutations in TP53. Wee1, a tyrosine kinase, regulates the cell cycle at the G2/M checkpoint. In TP53-deficient cells, the dependence on G2/M checkpoints increases. PD0166285 is the first reported drug with inhibitory activity against both Wee1 and PKMYT1. METHODS: Protein expression was determined by Western blot analysis. Cell proliferation was assessed using cell colony formation and CCK-8 assays. Cell cycle was performed by PI staining with flow cytometry. Apoptosis was evaluated using Annexin V-Phycoerythrin double staining and flow cytometry. DNA damage was detected through comet assay and immunofluorescence assay. In vivo, apoptosis and anti-tumor effects were assessed using the TUNEL assay, a nude mouse model, and immunohistochemistry (IHC). Co-immunoprecipitation assay was used to detect protein-protein interactions. We analyzed Wee1, PKMYT1, and Stat1 expression in pan-cancer studies using the Ualcan public database and assessed their prognostic implications with Kaplan-Meier curves. RESULT: PD0166285, a Wee1 inhibitor, effectively inhibits Wee1 activity, promoting cell entry into a mitotic crisis. Moreover, PD0166285 sensitizes cells to cisplatin, enhancing clinical outcomes. Our study demonstrated that PD016628 regulates the cell cycle through Rad51 and results in cell cycle arrest at the G2/M phase. We observed increased apoptosis in tumor cells treated with PD0166285, particularly when combined with cisplatin, indicating an enhanced apoptotic response. The upregulation of γ-H2AX serves as an indicator of mitotic catastrophe. Co-immunoprecipitation and data analysis revealed that apoptosis in LUSC is mediated through the Stat1 pathway, accompanied by decreased levels of Socs3. Furthermore, IHC staining confirmed significant differences in the expression of Phospho-CDK1 and γ-H2AX in LUSCs, suggesting involvement in DNA damage. CONCLUSIONS: In summary, our study suggests that PD0166285, an inhibitor of Wee1, sensitizes LUSC cells to cisplatin and modulates DNA damage and apoptosis pathways through Rad51 and Stat1, respectively. These findings highlight the combination of PD0166285 and cisplatin as a promising therapeutic approach for treating LUSC.

UAdam: Unified Adam-Type Algorithmic Framework for Nonconvex Optimization.

Adam-type algorithms have become a preferred choice for optimization in the deep learning setting; however, despite their success, their convergence is still not well understood. To this end, we introduce a unified framework for Adam-type algorithms, termed UAdam. It is equipped with a general form of the second-order moment, which makes it possible to include Adam and its existing and future variants as special cases, such as NAdam, AMSGrad, AdaBound, AdaFom, and Adan. The approach is supported by a rigorous convergence analysis of UAdam in the general nonconvex stochastic setting, showing that UAdam converges to the neighborhood of stationary points with a rate of O(1/T). Furthermore, the size of the neighborhood decreases as the parameter ß1 increases. Importantly, our analysis only requires the first-order momentum factor to be close enough to 1, without any restrictions on the second-order momentum factor. Theoretical results also reveal the convergence conditions of vanilla Adam, together with the selection of appropriate hyperparameters. This provides a theoretical guarantee for the analysis, applications, and further developments of the whole general class of Adam-type algorithms. Finally, several numerical experiments are provided to support our theoretical findings.

Long-term oncological outcomes of 3D versus 2D laparoscopic gastrectomy for gastric cancer: a randomized clinical trial.

BACKGROUND: Laparoscopy-assisted gastrectomy (LG) is rapidly gaining popularity owing to its minimal invasiveness. Previous studies have found that compared with two-dimensional (2D)-LG, three-dimensional (3D)-LG showed better short-term outcomes. However, the long-term oncological outcomes in patients with locally resectable gastric cancer (GC) remain controversial. METHODS: In this noninferiority, open-label, randomized clinical trial, a total of 438 eligible GC participants were randomly assigned in a 1:1 ratio to either 3D-LG or 2D-LG from January 2015 to April 2016. The primary endpoint was operating time, while the secondary endpoints included 5-year overall survival (OS), disease-free survival (DFS), and recurrence pattern. RESULTS: Data from 401 participants were included in the per-protocol analysis, with 204 patients in the 3D group and 197 patients in the 2D group. The 5-year OS and DFS rates were comparable between the 3D and 2D groups (5-year OS: 70.6% vs. 71.1%, Log-rank P = 0.743; 5-year DFS: 68.1% vs. 69.0%, log-rank P = 0.712). No significant differences were observed between the 3D and 2D groups in the 5-year recurrence rate (28.9% vs. 28.9%, P = 0.958) or recurrence time (mean time, 22.6 vs. 20.5 months, P = 0.412). Further stratified analysis based on the type of gastrectomy, postoperative pathological staging, and preoperative BMI showed that the 5-year OS, DFS, and recurrence rates of the 3D group in each subgroup were similar to those of the 2D group (all P > 0.05). CONCLUSIONS: For patients with locally resectable GC, 3D-LG performed by experienced surgeons in high-volume professional institutions can achieve long-term oncological outcomes comparable to those of 2D-LG. REGISTRATION NUMBER: NCT02327481 ( http://clinicaltrials.gov ).

Robot-assisted versus laparoscopic-assisted gastrectomy among malnourished patients with gastric cancer based on textbook outcome.

BACKGROUND: Textbook outcome (TO) has been widely employed as a comprehensive indicator to assess the short-term prognosis of patients with cancer. Preoperative malnutrition is a potential risk factor for adverse surgical outcomes in patients with gastric cancer (GC). This study aimed to compare the TO between robotic-assisted gastrectomy (RAG) and laparoscopic-assisted gastrectomy (LAG) in malnourished patients with GC. METHODS: According to the diagnostic consensus of malnutrition proposed by Global Leadership Initiative on Malnutrition (GLIM) and Nutrition Risk Index (NRI), 895 malnourished patients with GC who underwent RAG (n = 115) or LAG (n = 780) at a tertiary referral hospital between January 2016 and May 2021 were included in the propensity score matching (PSM, 1:2) analysis. RESULTS: After PSM, no significant differences in clinicopathological characteristics were observed between the RAG (n = 97) and LAG (n = 194) groups. The RAG group had significantly higher operative time and lymph nodes harvested, as well as significantly lower blood loss and hospital stay time compared to the LAG group. More patients in the RAG achieved TO. Logistic regression analysis revealed that RAG was an independent protective factor for achieving TO. There were more adjuvant chemotherapy (AC) cycles in the RAG group than in the LAG group. After one year of surgery, a higher percentage of patients (36.7% vs. 22.8%; P < 0.05) in the RAG group recovered from malnutrition compared to the LAG group. CONCLUSIONS: For malnourished patients with GC, RAG performed by experienced surgeons can achieved a higher rate of TO than those of LAG, which directly contributed to better AC compliance and a faster restoration of nutritional status.

Long-acting anti-inflammatory injectable DEX-Gel with sustained release and self-healing properties regulates TH1/TH2 immune balance for minimally invasive treatment of allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a prevalent immune-related allergic disease, and corticosteroid nasal sprays serve as the primary treatment for this patient population. However, their short duration of efficacy and frequent administration pose challenges, leading to drug wastage and potential adverse effects. To overcome these limitations, we devised a novel approach to formulate DEX-Gel by incorporating dexamethasone (DEX) into a blend of Pluronic F127, stearic acid (SA), and polyethylene glycol 400 (PEG400) to achieve sustained-release treatment for AR. RESULTS: Following endoscopic injection into the nasal mucosa of AR rats, DEX-Gel exhibited sustained release over a 14-day period. In vivo trials employing various assays, such as flow cytometry (FC), demonstrated that DEX-Gel not only effectively managed allergic symptoms but also significantly downregulated helper T-cells (TH) 2 and TH2-type inflammatory cytokines (e.g., interleukins 4, 5, and 13). Additionally, the TH1/TH2 cell ratio was increased. CONCLUSION: This innovative long-acting anti-inflammatory sustained-release therapy addresses the TH1/TH2 immune imbalance, offering a promising and valuable approach for the treatment of AR and other inflammatory nasal diseases.

Hydrogenation of CO2 to Light Olefins over ZnZrOx /SSZ-13.

Converting CO2 to olefins is an ideal route to achieve carbon neutrality. However, selective hydrogenation to light olefins, especially single-component olefin, while reducing CH4 formation remains a great challenge. Herein, we developed ZnZrOx /SSZ-13 tandem catalyst for the highly selective hydrogenation of CO2 to light olefins. This catalyst shows C2 = -C4 = and propylene selectivity up to 89.4 % and 52 %, respectively, while CH4 is suppressed down to 2 %, and there is no obvious deactivation. It is demonstrated that the isolated moderate Brønsted acid sites (BAS) of SSZ-13 promotes the rapid conversion of intermediate species derived from ZnZrOx , thereby enhancing the kinetic coupling of the reactions and inhibit the formation of alkanes and improve the light olefins selectivity. Besides, the weaker BAS of SSZ-13 promote the conversion of intermediates into aromatics with 4-6 methyl groups, which is conducive to the aromatics cycle. Accordingly, more propene can be obtained by elevating the Si/Al ratio of SSZ-13. This provides an efficient strategy for CO2 hydrogenation to light olefins with high selectivity.

YAP-TEAD mediates PPAR α-induced hepatomegaly and liver regeneration in mice.

BACKGROUND AND AIMS: Peroxisome proliferator-activated receptor α (PPARα, NR1C1) is a ligand-activated nuclear receptor involved in the regulation of lipid catabolism and energy homeostasis. PPARα activation induces hepatomegaly and plays an important role in liver regeneration, but the underlying mechanisms remain unclear. APPROACH AND RESULTS: In this study, the effect of PPARα activation on liver enlargement and regeneration was investigated in several strains of genetically modified mice. PPARα activation by the specific agonist WY-14643 significantly induced hepatomegaly and accelerated liver regeneration after 70% partial hepatectomy (PHx) in wild-type mice and Pparafl/fl mice, while these effects were abolished in hepatocyte-specific Ppara-deficient (PparaΔHep ) mice. Moreover, PPARα activation promoted hepatocyte hypertrophy around the central vein area and hepatocyte proliferation around the portal vein area. Mechanistically, PPARα activation regulated expression of yes-associated protein (YAP) and its downstream targets (connective tissue growth factor, cysteine-rich angiogenic inducer 61, and ankyrin repeat domain 1) as well as proliferation-related proteins (cyclins A1, D1, and E1). Binding of YAP with the PPARα E domain was critical for the interaction between YAP and PPARα. PPARα activation further induced nuclear translocation of YAP. Disruption of the YAP-transcriptional enhancer factor domain family member (TEAD) association significantly suppressed PPARα-induced hepatomegaly and hepatocyte enlargement and proliferation. In addition, PPARα failed to induce hepatomegaly in adeno-associated virus-Yap short hairpin RNA-treated mice and liver-specific Yap-deficient mice. Blockade of YAP signaling abolished PPARα-induced hepatocyte hypertrophy around the central vein area and hepatocyte proliferation around the portal vein area. CONCLUSIONS: This study revealed a function of PPARα in regulating liver size and liver regeneration through activation of the YAP-TEAD signaling pathway. These findings have implications for understanding the physiological functions of PPARα and suggest its potential for manipulation of liver size and liver regeneration.

Induction of Sestrin2 by pterostilbene suppresses ethanol-triggered hepatocyte senescence by degrading CCN1 via p62-dependent selective autophagy.

Hepatocyte senescence is a key event participating in the progression of alcoholic liver disease. Autophagy is a critical biological process that controls cell fates by affecting cell behaviors like senescence. Pterostilbene is a natural compound with hepatoprotective potential; however, its implication for alcoholic liver disease was not understood. This study was aimed to investigate the therapeutic effect of pterostilbene on alcoholic liver disease and elucidate the potential mechanism. Our results showed that pterostilbene alleviated ethanol-triggered hepatocyte damage and senescence. Intriguingly, pterostilbene decreased the protein abundance of cellular communication network factor 1 (CCN1) in ethanol-exposed hepatocytes, which was essential for pterostilbene to execute its anti-senescent function. In vivo studies verified the anti-senescent effect of pterostilbene on hepatocytes of alcohol-intoxicated mice. Pterostilbene also relieved senescence-associated secretory phenotype (SASP), redox imbalance, and steatosis by suppressing hepatic CCN1 expression. Mechanistically, pterostilbene-forced CCN1 reduction was dependent on posttranscriptional regulation via autophagy machinery but not transcriptional regulation. To be specific, pterostilbene restored autophagic flux in damaged hepatocytes and activated p62-mediated selective autophagy to recognize and lead CCN1 to autolysosomes for degradation. The protein abundance of Sestrin2 (SESN2), a core upstream modulator of autophagy pathway, was decreased in ethanol-administrated hepatocytes but rescued by co-treatment with pterostilbene. Induction of SESN2 protein by pterostilbene rescued ethanol-triggered autophagic dysfunction in hepatocytes, which then reduced senescence-associated markers, postponed hepatocyte senescence, and relieved alcohol-caused liver injury and inflammation. In conclusion, this work discovered a novel compound pterostilbene with therapeutic implications for alcoholic liver disease and uncover its underlying mechanism.

Critical roles of PU.1/cathepsin S activation in regulating inflammatory responses of macrophages in periodontitis.

OBJECTIVE: To determine the critical roles of PU.1/cathepsin S activation in regulating inflammatory responses of macrophages during periodontitis. BACKGROUND: Cathepsin S (CatS) is a cysteine protease and exerts important roles in the immune response. Elevated CatS has been found in the gingival tissues of periodontitis patients and is involved in alveolar bone destruction. However, the underlying mechanism of CatS-driven IL-6 production in periodontitis remains unclear. METHODS: Western blot was applied to measure mature cathepsin S(mCatS) and IL-6 expression in gingival tissues from periodontitis patients and RAW264.7 cells exposed to lipopolysaccharide from Porphyromonas gingivalis (P.g. LPS). Immunofluorescence was applied to confirm the localization of PU.1, and CatS in the gingival tissues of periodontitis patients. ELISA was performed to determine IL-6 production by the P.g. LPS-exposed RAW264.7 cells. Knockdown by shRNA was used to determine the effects of PU.1 on p38/ nuclear factor (NF)-κB activation, mCatS expression and IL-6 production in RAW264.7 cells. RESULTS: The expressions mCatS and IL-6 were significantly upregulated in gingival macrophages. In cultured RAW264.7 cells, increased mCatS and IL-6 protein paralleled the activation of p38 and NF-κB after exposure to P.g. LPS. CatS knockdown by shRNA significantly decreased P.g. LPS-induced IL-6 expression and p38/NF-κB activation. PU.1 was significantly increased in P.g. LPS-exposed RAW264.7 cells, and PU.1 knockdown dramatically abolished the P.g. LPS-induced upregulation of mCatS and IL-6 and the activation of p38 and NF-κB. Furthermore, PU.1 and CatS colocalized in macrophages within the gingival tissues of periodontitis patients. CONCLUSION: PU.1-dependent CatS drives IL-6 production in macrophages by activating p38 and NF-κB in periodontitis.

Long-term treatment with the mPXR agonist PCN promotes hepatomegaly and lipid accumulation without hepatocyte proliferation in mice.

Pregnane X receptor (PXR) is highly expressed in the liver and plays a pivotal role in xenobiotic and endobiotic metabolism. We previously reported that PXR activation by its specific mouse agonist pregnenolone 16α-carbonitrile (PCN) significantly induces liver enlargement and lipid accumulation. However, the effect of long-term PCN treatment on PXR and mouse liver is still unknown. This study aimed to explore the influence of long-term administration of PCN on mouse liver and hepatic lipid homeostasis. Male C57BL/6 mice were injected intraperitoneally with PCN (100 mg/kg once a week) for 42 weeks. Serum and liver samples were collected for biochemical and histological analysis. PXR activation was investigated by Western blot. Ultra-high-performance liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (UHPLC-ESI-HRMS)-based lipidomics analysis was performed to explore the change in different lipid categories. The results showed that long-term treatment with PCN significantly promoted hepatomegaly without hepatocyte proliferation and enlargement. Long-term treatment with PCN did not upregulate PXR target proteins in mice, and there was no significant upregulation of CYP3A11, CYP2B10, UGT1A1, MRP2, or MRP4. Lipidomics analysis showed obvious hepatic lipid accumulation in the PCN-treated mice, and the most significant change was found in triglycerides (TGs). Additionally, long-term treatment with PCN had no risk for carcinogenesis. These findings demonstrated that long-term PCN treatment induces hepatomegaly and lipid accumulation without hepatocyte proliferation or enlargement.

Genome Identification and Evolutionary Analysis of LBD Genes and Response to Environmental Factors in Phoebe bournei.

Phoebe bournei is nationally conserved in China due to its high economic value and positive effect on the ecological environment. P. bournei has an excellent wood structure, making it useful for industrial and domestic applications. Despite its importance, there are only a few studies on the lateral organ boundary domain (LBD) genes in P. bournei. The LBD gene family contributes to prompting rooting in multiple plant species and therefore supports their survival directly. To understand the LBD family in P. bournei, we verified its characteristics in this article. By comparing the sequences of Arabidopsis and identifying conserved domains and motifs, we found that there were 38 members of the LBD family in P. bournei, which were named PbLBD1 to PbLBD38. Through evolutionary analysis, we found that they were divided into two different populations and five subfamilies in total. The LBD gene family in P. bournei (Hemsl.) Yang species had two subfamilies, including 32 genes in Class I and 6 genes in Class II. It mainly consists of a Lateral Organ Boundary (LOB) conservative domain, and the protein structure is mostly "Y"-shaped. The gene expression pattern of the LBD gene family showed that the LBD genes were mainly expressed in lateral organs of plants, such as flowers and fruits. The response of LBD transcription factors to red and blue light was summarized, and several models of optogenetic expression regulation were proposed. The effect of regulatory mechanisms on plant rooting was also predicted. Moreover, quantitative real-time PCR (qRT-PCR) revealed that most PbLBDs were differentially expressed under cold, heat, drought, and salt stresses, indicating that PbLBDs might play different functions depending on the type of abiotic stress. This study provides the foundation for further research on the function of LBD in this tree species in the future.

Insights into the mechanism of the deterioration of mainstream partial nitritation/anammox under low residual ammonium.

Residual ammonium is a critical parameter affecting the stability of mainstream partial nitritation/anammox (PN/A), but the underlying mechanism remains unclear. In this study, mainstream PN/A was established and operated with progressively decreasing residual ammonium. PN/A deteriorated as the residual ammonium decreased to below 5 mg/L, and this was paralleled by a significant loss in anammox activity in situ and an increasing nitrite oxidation rate. Further analysis revealed that the low-ammonium condition directly decreased anammox activity in situ via two distinct mechanisms. First, anammox bacteria were located in the inner layer of the granular sludge, and thus were disadvantageous when competing for ammonium with ammonium-oxidizing bacteria (AOB) in the outer layer. Second, the complete ammonia oxidizer (comammox) was enriched at low residual ammonium concentrations because of its high ammonium affinity. Both AOB and comammox presented kinetic advantages over anammox bacteria. At high residual ammonium concentrations, nitrite-oxidizing bacteria (NOB) were effectively suppressed, even when their maximum activity was high due to competition for nitrite with anammox bacteria. At low residual ammonium concentrations, the decrease in anammox activity in situ led to an increase in nitrite availability for nitrite oxidation, facilitating the activation of NOB despite the dissolved oxygen limitation (0.15-0.35 mg/L) for NOB persisting throughout the operation. Therefore, the deterioration of mainstream PN/A at low residual ammonium was primarily triggered by a decline in anammox activity in situ. This study provides novel insights into the optimized design of mainstream PN/As in engineering applications.

Compact photoacoustic spectrophone for simultaneously monitoring the concentrations of dichloromethane and trichloromethane with a single acoustic resonator.

Chlorinated hydrocarbons are frequently used as reagents and organic solvents in different industrial processes. Real-time detection of chlorinated hydrocarbons, as toxic air pollutants and carcinogenic species, is an important requirement for various environmental and industrial applications. In this study, a compact photoacoustic (PA) spectrophone based on a single acoustic resonator for simultaneous detection of trichloromethane (CHCl3) and dichloromethane (CH2Cl2) is first reported by employing a low-cost distributed feedback (DFB) laser emitting at 1684 nm. In consideration of the significant overlapping of absorption spectral from trichloromethane and dichloromethane, the multi-linear regression method was used to calculate the concentrations of CHCl3 and CH2Cl2 with special characterization of the absorption profile. The current modulation amplitude and detection phase in the developed PA spectrophone was optimized for high sensitivity of individual components. The measurement interference of CHCl3 and CH2Cl2 on each other was investigated for accurate detection, respectively. For field measurements, all optical elements were integrated into a 40 cm × 40 cm × 20 cm chassis. This paper provides an experimental verification which strongly recommends this sensor as a compact photoacoustic field sensor system for chlorinated hydrocarbon detection in different applications.

PXR mediates mifepristone-induced hepatomegaly in mice.

Mifepristone (Mif), an effective synthetic steroidal antiprogesterone drug, is widely used for medical abortion and pregnancy prevention. Due to its anti-glucocorticoid effect, high-dose Mif is also used to treat Cushing's syndrome. Mif was reported to active pregnane X receptor (PXR) in vitro and PXR can induce hepatomegaly via activation and interaction with yes-associated protein (YAP) pathway. High-dose Mif was reported to induce hepatomegaly in rats and mice, but the underlying mechanism remains unclear. Here, the role of PXR was studied in Mif-induced hepatomegaly in C57BL/6 mice and Pxr-knockout mice. The results demonstrated that high-dose Mif (100 mg · kg-1 · d-1, i.p.) treatment for 5 days significantly induced hepatomegaly with enlarged hepatocytes and promoted proliferation, but low dose of Mif (5 mg · kg-1 · d-1, i.p.) cannot induce hepatomegaly. The dual-luciferase reporter gene assays showed that Mif can activate human PXR in a concentration-dependent manner. In addition, Mif could promote nuclear translocation of PXR and YAP, and significantly induced the expression of PXR, YAP, and their target proteins such as CYP3A11, CYP2B10, UGT1A1, ANKRD, and CTGF. However, Mif (100 mg · kg-1 · d-1, i.p.) failed to induce hepatomegaly in Pxr-knockout mice, as well as hepatocyte enlargement and proliferation, further indicating that Mif-induced hepatomegaly is PXR-dependent. In summary, this study demonstrated that PXR-mediated Mif-induced hepatomegaly in mice probably via activation of YAP pathway. This study provides new insights in Mif-induced hepatomegaly, and provides novel evidence on the crucial function of PXR in liver enlargement and regeneration.

Hepatic Vps33b deficiency aggravates cholic acid-induced cholestatic liver injury in male mice.

Vacuolar protein sorting 33B (VPS33B) is important for intracellular vesicular trafficking process and protein interactions, which is closely associated with the arthrogryposis, renal dysfunction, and cholestasis syndrome. Our previous study has shown a crucial role of Vps33b in regulating metabolisms of bile acids and lipids in hepatic Vps33b deficiency mice with normal chow, but it remains unknown whether VPS33B could contribute to cholestatic liver injury. In this study we investigated the effects of hepatic Vps33b deficiency on bile acid metabolism and liver function in intrahepatic cholestatic mice. Cholestasis was induced in Vps33b hepatic knockout and wild-type male mice by feeding 1% CA chow diet for 5 consecutive days. We showed that compared with the wild-type mice, hepatic Vps33b deficiency greatly exacerbated CA-induced cholestatic liver injury as shown in markedly increased serum ALT, AST, and ALP activities, serum levels of total bilirubin, and total bile acid, as well as severe hepatocytes necrosis and inflammatory infiltration. Target metabolomics analysis revealed that hepatic Vps33b deficiency caused abnormal profiles of bile acids in cholestasis mice, evidenced by the upregulation of conjugated bile acids in serum, liver, and bile. We further demonstrated that the metabolomics alternation was accompanied by gene expression changes in bile acid metabolizing enzymes and transporters including Cyp3a11, Ugt1a1, Ntcp, Oatp1b1, Bsep, and Mrp2. Overall, these results suggest a crucial role of hepatic Vps33b deficiency in exacerbating cholestasis and liver injury, which is associated with the altered metabolism of bile acids.

Long Noncoding RNA DANCR Regulates Cell Proliferation by Stabilizing SOX2 mRNA in Nasopharyngeal Carcinoma.

The long noncoding RNA DANCR (differentiation antagonizing non-protein coding RNA) displays aberrant expression in various cancers. However, its clinical value and functional mechanisms in nasopharyngeal carcinoma (NPC) remain poorly understood. We found that DANCR is dramatically up-regulated in human NPC, and that it is an indicator for poor survival prognosis. DANCR knockdown suppressed cell proliferation, colony formation in vitro, and tumorigenicity in vivo. Mechanistic analyses demonstrated that DANCR could bind to RNA-binding protein 3 (RBM3) protein and stabilize SOX2 mRNA, resulting in NPC cell proliferation. Our findings indicate that DANCR functions as an oncogene and a potential therapeutic target for NPC.

Iterative difference deblurring algorithm for linear computed laminography.

Linear Computed Laminography (LCL) is used to yield slice images of plate-like objects (PLO) for the advantage of short exposure time, high control precision and low cost. Shift and Add (SAA) is a widely used reconstruction algorithm for LCL. One limitation of SAA is that the reconstructed image of the in-focus layer (IFL) contains information from off-focus layers (OFL), resulting in inter-slice aliasing and blurring. In this paper, an Iterative Difference Deblurring (IDD) algorithm based on LCL is proposed to reduce the blur in reconstructed images. The core idea of the IDD algorithm is: contributions from OFL are subtracted from the projection data to remove the blur from the IFL. The corrected projections are then reconstructed using the SAA to remove the superimposed contributions of OFL from the IFL. An iterative approach is utilized to adjust a weighting factor applied during the subtraction stage. The results demonstrate that IDD algorithm can achieve PLO reconstruction in the LCL system under extremely sparse sampling conditions, and can effectively reduce the inter-slice aliasing and blurring.

Inelastic hyperspectral Scheimpflug lidar for microalgae classification and quantification.

An inelastic hyperspectral Scheimpflug lidar system was developed for microalgae classification and quantification. The correction for the refraction at the air-glass-water interface was established, making our system suitable for aquatic environments. The fluorescence spectrum of microalgae was extracted by principal component analysis, and seven species of microalgae from different phyla have been classified. It was verified that when the cell density of Phaeocystis globosa was in the range of ${{1}}{{{0}}^4}\sim{{1}}{{{0}}^6}\;{\rm{cell}}\;{\rm{m}}{{\rm{L}}^{- 1}}$, the cell density had a linear relationship with the fluorescence intensity. The experimental results show our system can identify and quantify microalgae, with application prospects for microalgae monitoring in the field environment and early warning of red tides or algal blooms.

Pregnane X Receptor Regulates Liver Size and Liver Cell Fate by Yes-Associated Protein Activation in Mice.

Activation of pregnane X receptor (PXR), a nuclear receptor that controls xenobiotic and endobiotic metabolism, is known to induce liver enlargement, but the molecular signals and cell types responding to PXR-induced hepatomegaly remain unknown. In this study, the effect of PXR activation on liver enlargement and cell change was evaluated in several strains of genetically modified mice and animal models. Lineage labeling using AAV-Tbg-Cre-treated Rosa26EYFP mice or Sox9-CreERT , Rosa26EYFP mice was performed and Pxr-null mice or AAV Yap short hairpin RNA (shRNA)-treated mice were used to confirm the role of PXR or yes-associated protein (YAP). Treatment with selective PXR activators induced liver enlargement and accelerated regeneration in wild-type (WT) and PXR-humanized mice, but not in Pxr-null mice, by increase of cell size, induction of a regenerative hybrid hepatocyte (HybHP) reprogramming, and promotion of hepatocyte and HybHP proliferation. Mechanistically, PXR interacted with YAP and PXR activation induced nuclear translocation of YAP. Blockade of YAP abolished PXR-induced liver enlargement in mice. Conclusion: These findings revealed a function of PXR in enlarging liver size and changing liver cell fate by activation of the YAP signaling pathway. These results have implications for understanding the physiological functions of PXR and suggest the potential for manipulation of liver size and liver cell fate.

Classification, identification, and growth stage estimation of microalgae based on transmission hyperspectral microscopic imaging and machine learning.

A transmission hyperspectral microscopic imager (THMI) that utilizes machine learning algorithms for hyperspectral detection of microalgae is presented. The THMI system has excellent performance with spatial and spectral resolutions of 4 µm and 3 nm, respectively. We performed hyperspectral imaging (HSI) of three species of microalgae to verify their absorption characteristics. Transmission spectra were analyzed using principal component analysis (PCA) and peak ratio algorithms for dimensionality reduction and feature extraction, and a support vector machine (SVM) model was used for classification. The average accuracy, sensitivity and specificity to distinguish one species from the other two species were found to be 94.4%, 94.4% and 97.2%, respectively. A species identification experiment for a group of mixed microalgae in solution demonstrates the usability of the classification method. Using a random forest (RF) model, the growth stage in a phaeocystis growth cycle cultivated under laboratory conditions was predicted with an accuracy of 98.1%, indicating the feasibility to evaluate the growth state of microalgae through their transmission spectra. Experimental results show that the THMI system has the capability for classification, identification and growth stage estimation of microalgae, with strong potential for in-situ marine environmental monitoring and early warning detection applications.