Activation of TAZ by XMU-MP-1 inhibits osteoclastogenesis and attenuates ovariectomy-induced cancellous bone loss.

Osteoporosis is a metabolic bone loss disorder usually accompanied by overactivated osteoclast formation and increased bone resorption. Transcriptional co-activator with PDZ-binding motif (TAZ) is an emerging potential target for the treatment of osteoporosis. Our previous research showed that TAZ overexpression inhibited osteoclast formation while TAZ silencing had the opposite effect. In addition, TAZ knockout in mouse osteoclasts induced osteoporosis in animal experiments. XMU-MP-1 (XMU) is a selective MST1/2 inhibitor that can theoretically activate TAZ; however, its effect on osteoporosis remains unknown. In this study, we found that XMU treatment significantly increased TAZ expression in osteoclasts and inhibited osteoclast formation in vitro; however, this inhibitory effect was eliminated after the deletion of TAZ. Furthermore, XMU treatment upregulated TAZ expression in osteoclasts and alleviated ovariectomy (OVX)-induced osteoporosis in bilateral OVX mouse models. These findings suggest that XMU can effectively activate TAZ and that pharmacological activation of TAZ may be a promising option for the treatment of osteoporosis.

Synthesis of Mesoporous Eu3+-Doped Zinc/Silicate Phosphors for Highly Selective and Sensitive Detection of Sulfide Ions.

A mesoporous Eu3+-doped zinc/silicate phosphor with a large surface area (>100 m2g-1) and amorphous structure was prepared in an aqueous solution without using any organic template. The residual concentration of the Zn2+ ion in the filtrate is lower than the standard of effluent 3.5 ppm under a pH 8-11 preparation condition. When a sulfide ion (S2-) is present in aqueous solution, the phosphor can react with the sulfide ion to transform from the amorphous structure to the crystalline ZnS, which causes structural transformation and a subsequent decrease in luminescent intensity. This distinct phosphor with a high surface area and amorphous structure can be applied through the structure transformation mechanism for highly selective and sensitive detection of the sulfide ions at low concentrations. In addition, the luminescent efficiency was obtained from adjustments in the pH value, calcination temperature, and Eu3+ ion concentration. The quenching efficiency, the limit of detection (CLOD), S2- ion selectivity, and phosphor regeneration ability were systematically explored in sulfide ion detection tests. Due to the novel S2- ion-induced structural transformation, we found that the amorphous Eu3+-doped zinc/silicate phosphors demonstrate a CLOD sensitivity as low as 1.8 × 10-7 M and a high Stern-Volmer constant (KSV) of 3.1 × 104 M-1. Furthermore, the phosphors were easily regenerated through simple calcination at 500 °C and showed a KSV value of 1.4 × 104 M-1. Overall, the Eu3+-doped zinc/silicates showed many advantageous properties for detecting sulfide ions, including low toxicity, green synthesis, good selectivity, high sensitivity, and good renewability.

A brain-tumor neural circuit controls breast cancer progression in mice.

Tumor burden, considered a common chronic stressor, can cause widespread anxiety. Evidence suggests that cancer-induced anxiety can promote tumor progression, but the underlying neural mechanism remains unclear. Here, we used neuroscience and cancer tools to investigate how the brain contributes to tumor progression via nerve-tumor crosstalk in a mouse model of breast cancer. We show that tumor-bearing mice exhibited significant anxiety-like behaviors and that corticotropin-releasing hormone (CRH) neurons in the central medial amygdala (CeM) were activated. Moreover, we detected newly formed sympathetic nerves in tumors, which established a polysynaptic connection to the brain. Pharmacogenetic or optogenetic inhibition of CeMCRH neurons and the CeMCRH→lateral paragigantocellular nucleus (LPGi) circuit significantly alleviated anxiety-like behaviors and slowed tumor growth. Conversely, artificial activation of CeMCRH neurons and the CeMCRH→LPGi circuit increased anxiety and tumor growth. Importantly, we found alprazolam, an antianxiety drug, to be a promising agent for slowing tumor progression. Furthermore, we show that manipulation of the CeMCRH→LPGi circuit directly regulated the activity of the intratumoral sympathetic nerves and peripheral nerve-derived norepinephrine, which affected tumor progression by modulating antitumor immunity. Together, these findings reveal a brain-tumor neural circuit that contributes to breast cancer progression and provide therapeutic insights for breast cancer.

Effects of silicate application on rice growth, yield and quality under nighttime warming in southern China.

The main feature of climate warming is that nighttime warming is higher than the daytime warming. Nighttime warming reduced single rice production in southern China, while silicate application increased rice yield and stress resistance. It is still unclear regarding the effects of silicate application on growth, yield, and especially quality in rice under nighttime warming. We performed a field simulation experiment to investigate the effects of silicate application on tiller number, biomass, yield and quality of rice. Warming was set at two levels, ambient temperature (control, CK) and nighttime warming (NW). The open passive nighttime warming method was used, with rice canopy being covered with aluminum foil reflective film at night (19:00-6:00) to simulate nighttime warming. Silicate fertilizer (steel slag) was applied at two levels, i.e., Si0(0 kg SiO2·hm-2) and Si1(200 kg SiO2·hm-2). The results showed that, compared with the control (ambient temperature), average temperature at nighttime on rice canopy and at 5 cm soil layer increased by 0.51-0.58 ℃ and 0.28-0.41 ℃ during rice growing season, respectively. Nighttime warming decreased tiller number and chlorophyll content by 2.5%-15.9% and 0.2%-7.7%, respectively. In contrast, silicate application increased tiller number and chlorophyll content by 1.7%-16.2% and 1.6%-16.6%, respectively. Under nighttime warming, silicate application increased dry weight of shoot, total dry weight of the whole plant, and yield at grain filling-maturity stage by 64.1%, 55.3%, and 7.1%, respectively. Under nighttime warming, silicate application significantly increased milled rice rate, head rice rate, and total starch content by 2.3%, 2.5%, and 41.8%, respectively. Nighttime warming reduced rice yield by decreasing the number of effective panicles, seed setting rate, and 1000-grain weight, but increasing empty grains. Silicate application increased rice yield by increasing the number of effective panicles, filled grains per panicle, seed setting rate and 1000-grain weight, but reducing empty grains. In conclusion, silicate application could effectively alleviate the suppressive effects of nighttime warming on growth, yield, and quality of single rice in Southern China.

Temporal variations of 7Be and 210Pb activity concentrations in the atmospheric aerosols during 2018-2019 in Beijing, China and their correlations with meteorological parameters.

In order to establish a regional database on natural radioactivity, a series of measurements of 713 atmospheric aerosol samples collected on filters over a two-year period (2018-2019) in center of Beijing, northeastern China have been performed to analyze 7Be and 210Pb activity concentrations. The mean activity concentrations of 7Be and 210Pb were found to be 7.10 ± 2.44 mBq m-3 and 2.93 ± 1.52 mBq m-3, respectively. Both the radionuclides exhibited strong seasonal variations, with maximum concentration of 7Be occurring in the spring and that of 210Pb in the winter. The concentration of both the radionuclides was minimum in the rainy summer. Higher 7Be concentration in the spring was mainly caused by the stratosphere to troposphere exchange. Higher 210Pb concentration during winter was maybe attributed to the combustion processes in heating systems and the ingression of continental air masses resulted from winds originating from northwest. The dependence of the activity concentrations of 7Be and 210Pb with meteorological parameters such as rainfall, temperature, and humidity was studied through linear correlation analysis. Statistically significant negative correlations were observed between 7Be and 210Pb activity concentrations with rainfall, respectively, which suggested that the removal mechanisms of these two radionuclides were similar. Lead-210 showed statistically significant correlations with temperature, humidity and PM10. A comparison of the data obtained in the present study for Beijing with the northern hemisphere literature values of 7Be and 210Pb in the atmospheric aerosols showed that the values were smaller than the ones observed in the present study. Overall, the study provides an improved understanding of the temporal variability and correlation of 7Be and 210Pb concentrations in the atmosphere in center of Beijing, northeastern China.

Silybin regulates P450s activity by attenuating endoplasmic reticulum stress in mouse nonalcoholic fatty liver disease.

Cytochrome P450s are important phase I metabolic enzymes located on endoplasmic reticulum (ER) involved in the metabolism of endogenous and exogenous substances. Our previous study showed that a hepatoprotective agent silybin restored CYP3A expression in mouse nonalcoholic fatty liver disease (NAFLD). In this study we investigated how silybin regulated P450s activity during NAFLD. C57BL/6 mice were fed a high-fat-diet (HFD) for 8 weeks to induce NAFLD, and were administered silybin (50, 100 mg ·kg-1 ·d-1, i.g.) in the last 4 weeks. We showed that HFD intake induced hepatic steatosis and ER stress, leading to significant inhibition on the activity of five primary P450s including CYP1A2, CYP2B6, CYP2C19, CYP2D6, and CYP3A in liver microsomes. These changes were dose-dependently reversed by silybin administration. The beneficial effects of silybin were also observed in TG-stimulated HepG2 cells in vitro. To clarify the underlying mechanism, we examined the components involved in the P450 catalytic system, membrane phospholipids and ER membrane fluidity, and found that cytochrome b5 (cyt b5) was significantly downregulated during ER stress, and ER membrane fluidity was also reduced evidenced by DPH polarization and lower polyunsaturated phospholipids levels. The increased ratios of NADP+/NADPH and PC/PE implied Ca2+ release and disruption of cellular Ca2+ homeostasis resulted from mitochondria dysfunction and cytochrome c (cyt c) release. The interaction between cyt c and cyt b5 under ER stress was an important reason for P450s activity inhibition. The effect of silybin throughout the whole course suggested that it regulated P450s activity through its anti-ER stress effect in NAFLD. Our results suggest that ER stress may be crucial for the inhibition of P450s activity in mouse NAFLD and silybin regulates P450s activity by attenuating ER stress.

Dual protective role of velutin against articular cartilage degeneration and subchondral bone loss via the p38 signaling pathway in murine osteoarthritis.

Osteoarthritis (OA) is a common degenerative joint condition associated with inflammation and characterized by progressive degradation of the articular cartilage and subchondral bone loss in the early stages. Inflammation is closely associated with these two major pathophysiological changes in OA. Velutin, a flavonoid family member, reportedly exerts anti-inflammatory effects. However, the therapeutic effects of velutin in OA have not yet been characterized. In this study, we explore the effects of velutin in an OA mouse model. Histological staining and micro-CT revealed that velutin had a protective effect against cartilage degradation and subchondral bone loss in an OA mouse model generated by surgical destabilization of the medial meniscus (DMM). Additionally, velutin rescued IL-1ß-induced inflammation in chondrocytes and inhibited RANKL-induced osteoclast formation and bone resorption in vitro. Mechanistically, the p38 signaling pathway was found to be implicated in the inhibitory effects of velutin. Our study reveals the dual protective effects of velutin against cartilage degradation and subchondral bone loss by inhibiting the p38 signaling pathway, thereby highlighting velutin as an alternative treatment for OA.

Use of Autologous Serum Eye Drops with Contact Lenses in the Treatment of Chemical Burn-Induced Bilateral Corneal Persistent Epithelial Defects.

OBJECTIVE: We aim to evaluate the clinical effect of combined topical 20% autologous serum eye drops (ASEs) along with silicone-hydrogel soft contact lenses (SCLs) in the treatment of chemical burn-induced bilateral corneal persistent epithelial defects (PEDs) and to review the literature of related studies. METHODS: From January 1, 2017, to December 31, 2019, we conducted a retrospective chart review of 8 patients with chemical burn-induced bilateral corneal PEDs who were unsuccessfully treated with conventional medical therapy and were then treated with combined topical 20% (v/v) ASEs and silicone-hydrogel CLs. The clinical effects and effectiveness of the combined treatment were evaluated. RESULTS: The bilateral corneal PEDs healed in all sixteen eyes of the eight patients within 2 weeks. The patients did not report any discomfort associated with the combined treatment. Improved ocular comfort/visual acuity and decreased conjunctival injection correlated with healing. No recurrent corneal epithelial breakdown was noted during the 3-month posttreatment follow-up. CONCLUSIONS: The combined treatment of silicone-hydrogel CLs and ASEs can help to stabilize the ocular surface and successfully treat chemical burn-induced bilateral corneal PEDs. It may be considered as an alternative treatment method for patients with bilateral chemical burn-induced corneal PEDs with potential corneal melting.

New dammarane-type triterpenoid saponins from Gynostemma pentaphyllum and their Sirt1 agonist activity.

Gynostemma pentaphyllum (Thunb.) Makino (Cucurbitaceae family) is a perennial creeping plant with a common Chinese name of "south ginseng". To date, more than 250 individual saponins with dammarane-type skeleton have been isolated from G. pentaphyllum. The purpose of this study was the isolation and structural characterization of novel, minor gypenosides from G. pentaphyllum and evaluation of their Sirt1 agonist activity. Individual saponins from G. pentaphyllum were isolated and purified by a variety of chromatography techniques, and their structures were elucidated by means of various spectroscopic analysis and comparision with the reported data. Sirt1 enzyme activity detection kit was used to preliminarily evaluate the Sirt1 agonist activity of thirty three individual saponins purified from G. pentaphyllum. Fourteen new triterpenoid saponins named gypenoside CII-CXV (1-14) along with twenty six known compounds (15-40) were isolated from G. pentaphyllum. Thirty three of all the isolates were screened for Sirt1 agonist activity, and the results showed that three dammarane-type saponins (2, 18, 37) and one cucurbitane-type saponin 33 exhibited satisfactory Sirt1 agonist activity. These findings suggested that G. pentaphyllum was worthy of further investigation to find small molecule Sirt1 agonist and facilitate their utilization as "south ginseng".

New dammarane-type glycosides from Gynostemma pentaphyllum and their lipid-lowering activity.

Gynostemma pentaphyllum (Thunb.) Makino has a long history as food and diary supplement in China. At present, there are some products for hyperlipidemia in the market, including G. pentaphyllum tea, healthy wine and healthy food. In order to discover proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, fourteen new triterpenoid saponins named gypenoside LXXXVIII-CI (1-14) along with six known compounds (15-20) were isolated from G. pentaphyllum. Their structures were elucidated by means of various spectroscopic techniques. Eight isolates were evaluated the inhibitory effect on PCSK9 in HepG2 cells. The results showed that three dammarane-type glycosides (2, 3, 15) remarkably reduced PCSK9 expression at 10 µM concentration. These findings suggested that G. pentaphyllum was worthy of further investigation to find small molecule PCSK9 inhibitors and facilitate their utilization as functional food ingredients.

Responses of soil microbiome to steel corrosion.

The process of microbiologically influenced corrosion (MIC) in soils has received widespread attention. Herein, long-term outdoor soil burial experiments were conducted to elucidate the community composition and functional interaction of soil microorganisms associated with metal corrosion. The results indicated that iron-oxidizing (e.g., Gallionella), nitrifying (e.g., Nitrospira), and denitrifying (e.g., Hydrogenophaga) microorganisms were significantly enriched in response to metal corrosion and were positively correlated with the metal mass loss. Corrosion process may promote the preferential growth of the abundant microbes. The functional annotation revealed that the metabolic processes of nitrogen cycling and electron transfer pathways were strengthened, and also that the corrosion of metals in soil was closely associated with the biogeochemical cycling of iron and nitrogen elements and extracellular electron transfer. Niche disturbance of microbial communities induced by the buried metals facilitated the synergetic effect of the major MIC participants. The co-occurrence network analysis suggested possible niche correlations among corrosion related bioindicators.

[Effect of psoralen on rat osteoblasts injuries induced by TCP wear particles in vitro and its mechanism].

Objective: To investigate the effect and mechanism of psoralen on calvarial osteoblasts injuries caused by tricalcium phosphate (TCP) wear particles in vitro.Methods: Primary osteoblasts were obtained from the calvaria of neonatal SD rat by the series of digestion and were identified with ALP staining. Calvarial osteoblasts were treated with TCP wear particles for 48 h to establish the in vitro model of osteoblasts injuries. The rat osteoblasts were randomly divided into control group, TCP wear particles (0.1 mg/ml) group, psoralen treated (at the concentrations of 10-7, 10-6, 10-5 mol/L) groups. WST assay and the flow cytometry were used to detect the cell viability of osteoblasts and apoptosis, respectively. Chemical colorimetry was performed to examine ALP activity of osteobalsts. When the osteoblasts were treated for 14 day, mineral nodules formation was observed with alizarin red S staining. Western blot was applied to examine protein expressions of glucose regulated protein78/94(GRP78/94), inositol dependent enzyme 1 alpha (IREα), spliced X-box binding protein 1 (XBP1s) and phosphorylated c-Jun N-terminal kinase (p-JNK) in calvarial osteoblasts. Results: Compared with control group, the cell viability of osteoblasts, ALP activity and mineral nodules formation in TCP group were decreased significantly (P＜0.05), while the percentage of apoptosis and protein expressions of GRP78/94, IRE1α, XBP1 and p-JNK were obviously increased in calvarial osteoblasts (P＜0.05). Compared with TCP group, the injuries of calvarial osteoblasts and cell apoptosis in psoralen treated groups were obviously decreased (P＜0.05), and the expression levels of GRP78/94, IRE1α, XBP1 and p-JNK were down-regulated remarkably (P＜0.05). Conclusion: Psoralen prevents osteoblasts injuries caused by TCP wear particles through IRE1α-XBP1s-JNK signaling pathway activation.

Interpretations and comments for expert consensus on the diagnosis and treatment of heat stroke in China.

Heat stroke is the most severe type of heat illness, it is often accompanied by severe multiorgan damage and has a high fatality rate. In January 2020, based on new research evidence and the experiences of Chinese experts in heat stroke, the Expert Group of Heat Stroke Prevention and Treatment of the Chinese People's Liberation Army (PLA) and the Professional Committee of Critical Care Medicine of the Chinese PLA jointly issued a new Expert Consensus on the Diagnosis and Treatment of Heat Stroke in China. This article aims to interpret and supplement the major updates to the new consensus.

Microbial ingress and in vitro degradation enhanced by glucose on bioabsorbable Mg-Li-Ca alloy.

Biodegradable magnesium alloys are challenging to be implanted in patients with hyperglycemia and diabetes. A hypothesis is suggested that glucose accelerates microbial ingress and in vitro degradation of Mg-Li-Ca implants. Corrosion resistance and mechanical properties was demonstrated using electrochemical, hydrogen evolution and tensile tests. The bacteria from Hank's solution were isolated via 16S rRNA gene analysis. The results revealed that Mg-1Li-1Ca alloy exhibited different responses to Hank's solution with and without glucose. The solution acidity was ascribed to Microbacterium hominis and Enterobacter xiangfangensis, indicating that glucose promoted microbial activity and degradation and deterioration in mechanical property of Mg-1Li-1Ca alloy.

Chemical content and source apportionment of 36 heavy metal analysis and health risk assessment in aerosol of Beijing.

The concentration levels of 36 airborne heavy metals and atmospheric radioactivity in total suspended particulate (TSP) samples were measured to investigate the chemical characteristics, potential sources of aerosols, and health risk in Beijing, China, from September 2016 to September 2017. The TSP concentrations varied from 6.93 to 469.18 µg/m3, with a median of 133.97 µg/m3. The order for the mean concentrations of heavy metals, known as hazardous air pollutants (HAPs), was as follows: Mn > Pb > As > Cr > Ni > Se > Cd > Co > Sb > Hg > Be; Non-Designated HAPs Metals: Ca > Fe > Mg > Al > K > Na > Zn > P > Ba > Ti > Cu > Sr > B > Sn > I > V > Rb > Ce > Mo > Cs > Th > Ag > U > Pt. The median concentration of As was higher than China air quality standard (6 ng/m3). The gross α and ß concentration levels in aerosols were (1.84 ± 1.59) mBg/m3 and (1.15 ± 0.85) mBg/m3, respectively. The enrichment factor values of Cu, Ba, B, Ce, Tl, Cs, Pb, As, Cd, Sb, Hg, Fe, Zn, Sn, I, Mo, and Ag were higher than 10, which indicated enriched results from anthropogenic sources. Pb, As, and Cd are considered to originate from multiple sources; fireworks released Ba during China spring festival; Fe, Ce, and Cs may come from stable emissions such as industrial gases. The health risks from anthropogenic metals via inhalation, ingestion, and dermal pathway were estimated on the basis of health quotient as well as the results indicated that children faced the higher risk than adults during the research period. For adults, the health risk posed by heavy metals in atmospheric particles was below the acceptable level.

[Effects of solar radiation on CH4 emission in paddy field]. / 太阳辐射对稻田甲烷排放的影响.

Decrease in solar radiation is one of the main components of climate change. Studies aimed at examining the effects of decreased solar radiation on CH4 emission and estimation of CH4 emission based on hyperspectral data in paddy fields are still scarce. A field simulation experiment was conducted to investigate the effects of shading intensity on CH4 emission in a paddy field and rice canopy hyperspectral properties. CH4 emission flux was estimated with rice canopy hyperspectral data. The shading intensities were set at three levels, i.e. control (CK, no shading), light shading (S1, 60% of shading rate), and heavy shading (S2, 84% of shading rate). The results showed that shading significantly reduced CH4 emission. However, CH4 emission under heavy shading (S2) was higher than that under light shading (S1). The reflectance of the near-infrared spectrum on rice canopy from the jointing stage to grain filling stage was in the sequence of CK>S2>S1. The spectral reflectance on rice canopy was significantly and positively correlated with CH4 flux in the near-infrared band (699-1349 nm), with a correlation coefficient of 0.64 (P<0.01). The six vegetation indices were significantly correlated with CH4 flux. The correlation coefficient between Ratio Vegetation Index (RVI) and CH4 flux was the largest, with R2=0.84 (P<0.01). The stepwise regression model with RVI, Normalized Difference Vegetation Index (NDVI), and 507 nm original reflectance (Ρ507) parameters was the best one (fitting model R2=0.86, prediction model R2=0.85) for estimating CH4 emission.

The long non-coding RNA Linc-GALH promotes hepatocellular carcinoma metastasis via epigenetically regulating Gankyrin.

Hepatocellular carcinoma (HCC) is the most prevalent subtype of liver cancer, and it is characterized by high rate of metastasis and recurrence. Recent studies have boosted our understanding that Gankyrin contributes to both of these pathological properties, but the mechanisms underlying its aberrant regulation are poorly understood. Recently, many long noncoding RNAs (lncRNAs) have been reported to be involved in regulating the expression of oncogenes and anti-oncogenes through various mechanisms. Here, using transcriptome microarray analysis, we identified a long intergenic noncoding RNA termed Linc-GALH that was highly expressed and concordance with Gankyrin expression in HCC. In addition, we revealed that Linc-GALH was an independent unfavorable prognostic indicator for HCC, followed functional experiments showed that Linc-GALH promoted HCC cells migration and invasion in vitro, and enhanced lung metastasis ability of HCC cells in vivo. Mechanistically, we found that Linc-GALH could regulate the expression of Gankyrin through controlling the methylation status of Gankyrin by adjusting the ubiquitination status of DNMT1 in HCC. Collectively, our results demonstrated the role and functional mechanism of Linc-GALH in HCC, and indicated that Linc-GALH may act as a prognostic biomarker and potential therapeutic target for HCC.

Differential circRNA expression profiles in latent human cytomegalovirus infection and validation using clinical samples.

Human cytomegalovirus (HCMV) is an opportunistic prototypic beta-herpesvirus that can cause severe and even fatal diseases in immune-naive newborns and immunocompromised adults. Host-virus interactions occurring at the transcriptional and posttranscriptional levels are critical for establishing an HCMV latent or lytic infection, but the mechanisms remain poorly understood. Herein, we investigated the expression of circRNAs in human leukemia monocytes (THP-1 cells) latently infected with HCMV and explored the diagnostic value of circRNAs in children with HCMV infection. A total of 2,110 and 1,912 circRNAs were identified in mock-infected and HCMV latent-infected THP-1 cells, respectively. Of these, we identified 1,421 differently expressed circRNAs, of which 650 were upregulated and 771 were downregulated. The host genes corresponding to the differentially expressed circRNAs were mainly involved in the regulation of host cell secretion pathways, cell cycle, and cell apoptosis. The differentially expressed circRNAs had binding sites for microRNAs, suggesting an important role in the mechanism of HCMV latent infection. Furthermore, a clinical analysis showed that the expression levels of hsa_circ_0001445 and hsa_circ_0001206 were statistically significantly different in HCMV-infected patients vs. normal controls, suggesting that these circRNAs could potentially serve as biomarkers of HCMV-infection.

Long non-coding RNA LUCAT1 promotes tumourigenesis by inhibiting ANXA2 phosphorylation in hepatocellular carcinoma.

Long non-coding RNAs (lncRNAs) play essential roles in diverse biological processes; however, current understanding of the mechanism underlying the regulation of tumour proliferation and metastasis is limited. Lung cancer-associated transcript 1 (LUCAT1) has been reported in a variety of human cancers, while its role in hepatocellular carcinoma (HCC) remains unclear. This study aimed to determine the biological role and underlying mechanism of LUCAT1 on progression and metastasis in HCC cells and clinical specimens. Our results demonstrated that LUCAT1 was up-regulated in HCC tissues and cells. Loss- and gain-of-function studies revealed that LUCAT1 promotes the proliferation and metastasis of HCC cells in vitro and in vivo. Furthermore, RNA pulldown and Western blot assays indicated that LUCAT1 inhibited the phosphorylation of Annexin A2 (ANXA2) to reduce the degradation of ANXA2-S100A10 heterotetramer (AIIt), which in turn accelerated the secretion of plasminogen into plasmin, thereby resulting in the activation of metalloprotease proteins. In conclusion, we propose that LUCAT1 serves as a novel diagnostic and therapeutic target for HCC.

An Assessment of Upper Limits of Normal for ALT and the Impact on Evaluating Natural Course of Chronic Hepatitis B Virus Infection in Chinese Children.

BACKGROUND: The current upper limits of normal (ULN) for serum alanine aminotransferase (ALT) are increasingly challenged. We aimed to re-evaluate the ULN for ALT and assess the potential impact on the classification of natural course of chronic hepatitis B virus (HBV) infection in children. METHODS: Laboratory data obtained from three hospitals in China were retrospectively analysed. In total, 2054 children with chronic HBV infection and 8149 healthy children at age ≤18 years were included in the study. RESULTS: Age-specific and gender-specific ULNs for ALT, at averages of 30 U/L for boys and 24 U/L for girls, were calculated from the data of healthy children. Using the revised ULNs vs. the current ULNs (40-50 U/L), 31-60% vs. 9-17% of the 2054 HBV-infected children had an abnormal result as seen in their ALT baseline analysis, and the highest abnormality rate was seen in the infants. Data of 516 HBV-infected children were applied for the classification of clinical phase, 28.8% vs. 19.8% of the children were classified into the phases of hepatitis B e antigen (HBeAg-)positive/negative hepatitis. During a median follow-up of 62 months, 39 of 153 children underwent HBeAg seroconversion, whereas 3 of them had persistently "normal" ALT, according to the current ULN. CONCLUSIONS: The revision of ULN for ALT in children substantially impacts the classification of the natural course of chronic HBV infection. Mild ALT fluctuation is common during the stage childhood, suggesting a need to rethink the current conceptions of immune tolerance and natural course of chronic HBV infection in the children.