Direct ink writing 3D-printed optical waveguides for multi-layer interconnect.

Low-cost, short-range optical interconnect technology plays an indispensable role in high-speed board-level data communications. In general, 3D printing technology can easily and quickly produce optical components with free-form shapes, while the traditional manufacturing process is complicated and time-consuming. Here, we present a direct ink writing 3D-printing technology to fabricate optical waveguides for optical interconnects. The waveguide core is 3D printed optical polymethylmethacrylate (PMMA) polymer, with propagation loss of 0.21 dB/cm at 980 nm, 0.42 dB/cm at 1310 nm, and 1.08 dB/cm at 1550 nm, respectively. Furthermore, a high-density multilayer waveguide arrays, including a four-layer waveguide arrays with a total of 144 waveguide channels, is demonstrated. Error-free data transmission at 30 Gb/s is achieved for each waveguide channel, indicating that the printing method can produce optical waveguides with excellent optical transmission performance. We believe this simple, low-cost, highly flexible, and environmentally friendly method has great potential for high-speed short-range optical interconnects.

Antimony and naphthalene can be simultaneously leached from a combined contaminated soil using carboxymethyl-ß-cyclodextrin as a biodegradable eluant.

In this study, we have investigated the removal efficiency of antimony (Sb) and naphthalene (Nap) from a combined contaminated soil by carboxymethyl-ß-cyclodextrin (CMCD) leaching and reveal its remediation mechanisms by FTIR and 1H NMR analyses. The results show that the highest removal efficiencies of Sb and Nap were 94.82% and 93.59%, respectively, with a CMCD concentration of 15 g L-1 at a pH of 4 and a leaching rate of 2.00 mL min-1 over an interval-time of 12 h. The breakthrough curves show that CMCD had a stronger inclusion capacity of Nap than Sb, and Sb could enhance the adsorption capacity of Nap, while Nap weakened the adsorption of Sb during CMCD leaching. Furthermore, the FTIR analysis suggests that the removal of Sb from combined contaminated soil involved complexation with the carboxyl and hydroxyl groups on CMCD, and the NMR analysis suggests that the inclusion of Nap occurred. These results indicate that CMCD is a good eluant for remediating soil contaminated by a combination of heavy metals and polycyclic aromatic hydrocarbons (PAHs), and its remediation mechanisms depend on the complexation reactions between the surface functional groups and inclusion reactions in the internal cavities.

Combined impacts of algae-induced variations in water soluble organic matter and heavy metals on bacterial community structure in sediment from Chaohu Lake, a eutrophic shallow lake.

Many lakes are suffering from eutrophication and heavy metals-contamination. However, the combined impacts of algae bloom and its induced variations in heavy metals on microbial community in sediment from eutrophic lakes remain unclear. In this study, we performed field experiments to investigate how algae bloom impacted water soluble organic matter (WSOM) and heavy metals in sediment from Chaohu Lake, a eutrophic shallow lake, and probed their combined impacts on sediment bacterial community structure. The results showed that algae bloom increased WSOM quantity, in particular, the soluble microbial by-product-like (SMP) and fulvic acid-like (Fa-L) components markedly enhanced by 203.70 % and 70.17 %, respectively. We also found that algae bloom redistributed the spatial patterns of heavy metals and altered their chemical species in sediment, then promoted contamination degree and potential ecological risk of heavy metals in sediment. Moreover, sediment bacterial community richness and diversity obviously decreased after algae bloom, and the variance partitioning analysis (VPA) results showed that combined impacts of algae-induced changes in WSOM and heavy metals explained 66.56 % of the variations in bacterial community structure. These findings depicted how algae bloom influence sediment WSOM and heavy metals, and revealed the combined impacts of algae-induced variations on microbial community structure in shallow eutrophic lake.

Cinnamaldehyde microcapsules enhance bioavailability and regulate intestinal flora in mice.

The effects of cinnamaldehyde microcapsules on the concentration of cinnamaldehyde and its metabolites in plasma, urine, and feces, the antioxidant capacity, and the intestinal flora in male C57/BL6 mice were evaluated by oral administration for 7 weeks. Microencapsulation significantly increased the contents of cinnamaldehyde, cinnamyl alcohol, and methyl cinnamate in plasma and decreased those in urine and feces excretion (p < 0.05). In addition, microencapsulated cinnamaldehyde improved antioxidant capacity in liver, duodenum, and colon. Furthermore, 16S rRNA gene sequencing data suggested that microencapsulated cinnamaldehyde significantly improved the gut microbial richness and diversity, increased  the abundance of Bacteroides, Bacteroidetes/Firmicutes, unclassified_f_Lachnospiraceae, Lactobacillus, and Blautia genera, and decreased in Ruminococcaceae_UCG-014, Faecalibaculum, norank_f_Muribaculaceae, and Gordonibacter genera, which was accompanied by the increased contents of butyric acid in feces. Therefore, microencapsulated cinnamaldehyde may increase its bioavailability and regulate the balance of intestinal flora.

SOX11-dependent CATSPER1 expression controls colon cancer cell growth through regulation the PI3K/AKT signaling pathway.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors and the fourth leading cause of cancer death worldwide. Constitutive activation of the PI3K/AKT signaling pathway is a hallmark of colon tumor growth. CATSPER1 gene encodes a pore-forming and pH-sensing subunit of the CatSper Ca2+-permeable channel, a sperm-specific calcium channel essential for hyperactivated motility and male fertility. However, the function of CATSPER1 outside the male reproductive system is unclear. OBJECTIVE: This study was designed to explore whether CatSper exerted its functional role in the progress of CRC, and investigate the possible mechanisms. METHODS: Microarray data (GSE146587) from 6 patients diagnosed with stage III CRC post-surgery was analyzed by Limma R package. The Kaplan Meier plotter (KM plotter) database was used to assess the relevance of CATSPER1 mRNA expression to the overall survival (OS) rates in CRC. Western blot, real-time PCR and luciferase reporter assays were used to determine the SOX11-CATSPER1 axis in CRC cells. Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing was used to generate CATSPER1 knockout (KO) CRC cells. The proliferation of CRC cells was determined by BrdU incorporation and colony formation assays. The effect of CATSPER1 on CRC tumor growth in vivo was investigated in a mice tumor xenograft model. RESULTS: Here, we show that CATSPER1 expression was significantly up-regulated in CRC and elevated CATSPER1 was associated with poor overall survival (OS). Moreover, the transcription factor SOX11 (SRY-related high-mobility-group (HMG) box 11) activated CATSPER1 transcription in CRC cells. Functionally, we showed that CATSPER1 promoted CRC cells proliferation both in vitro and in vivo. At the molecular level, we demonstrated that CATSPER1 might maintain CRC malignant process partly through the activation of the PI3K/AKT signaling pathway. CONCLUSION: Increased CATSPER1 expression facilitates CRC cells proliferation, suggesting that targeting CATSPER1 might represent a promising strategy for colon cancer treatment.

Discovery of a Nur77-mediated cytoplasmic vacuolation and paraptosis inducer (4-PQBH) for the treatment of hepatocellular carcinoma.

Nur77, an orphan nuclear receptor, has antitumor activity in hepatocellular carcinoma (HCC). However, its antitumor mechanisms of action in HCC are complicated and rarely reported. Our recent work demonstrated that certain quinoline-Schiff-base derivatives were good Nur77 mediators that exerted excellent anti-HCC activities in vitro and in vivo. Interestingly, these compounds shared similar chemical structures, but they displayed different Nur77-targeted anticancer mechanisms of action. As a continuous work, we synthesized a series of 4-(quinoline-4-amino) benzoylhydrazide derivatives and evaluated their anti-HCC activity and binding affinity to Nur77 in vitro. Compound 4-PQBH emerged as the best Nur77 binder (KD = 1.17 µM) and has potentially selective cytotoxicity to HCC cells. Mechanistically, 4-PQBH extensively induced caspase-independent cytoplasmic vacuolization and paraptosis through Nur77-mediated ER stress and autophagy. Moreover, 4-PQBH exhibited an effective xenograft tumor inhibition by modulating Nur77-dependent cytoplasmic vacuolation and paraptosis. This paper is the first to disclose that chemotherapeutic agents targeting Nur77-mediated cytoplasmic vacuolization and paraptosis may provide a promising strategy to combat HCC that frequently evade the apoptosis program.

Secondary bloodstream infection in critically ill patients with COVID-19.

OBJECTIVE: Secondary infection, especially bloodstream infection, is an important cause of death in critically ill patients with COVID-19. We aimed to describe secondary bloodstream infection (SBI) in critically ill adults with COVID-19 in the intensive care unit (ICU) and to explore risk factors related to SBI. METHODS: We reviewed all SBI cases among critically ill patients with COVID-19 from 12 February 2020 to 24 March 2020 in the COVID-19 ICU of Jingmen First People's Hospital. We compared risk factors associated with bloodstream infection in this study. All SBIs were confirmed by blood culture. RESULTS: We identified five cases of SBI among the 32 patients: three with Enterococcus faecium, one mixed septicemia (E. faecium and Candida albicans), and one C. parapsilosis. There were no significant differences between the SBI group and non-SBI group. Significant risk factors for SBI were extracorporeal membrane oxygenation, central venous catheter, indwelling urethral catheter, and nasogastric tube. CONCLUSIONS: Our findings confirmed that the incidence of secondary infection, particularly SBI, and mortality are high among critically ill patients with COVID-19. We showed that long-term hospitalization and invasive procedures such as tracheotomy, central venous catheter, indwelling urethral catheter, and nasogastric tube are risk factors for SBI and other complications.

Comparison of the clinical characteristics and mortalities of severe COVID-19 patients between pre- and post-menopause women and age-matched men.

The mortality rate of young female COVID-19 patients is reported to be lower than that of young males but no significant difference in mortality was found between female and male COVID-19 patients aged over 65 years, and the underlying mechanism is unknown. We retrospectively analyzed clinical characteristics and outcomes of severely ill pre- and post-menopausal COVID-19 patients and compared with age-matched males. Of the 459 patients included, 141 aged ≤55, among whom 19 died (16 males vs. 3 females, p<0.005). While for patients >55 years (n=318), 115 died (47 females vs. 68 males, p=0.149). In patients ≤55 years old, the levels of NLR, median LDH, median c-reactive protein and procalcitonin were significantly higher while the median lymphocyte count and LCR were lower in male than in female (all p<0.0001). In patients over 55, these biochemical parameters were far away from related normal/reference values in the vast majority of these patients in both genders which were in contrast to that seen in the young group. It is concluded that the mortality of severely ill pre-menopausal but not post-menopausal COVID-19 female patients is lower than age-matched male. Our findings support the notion that estrogen plays a beneficial role in combating COVID-19.

[Formulation of technical guidelines in line with characteristics and principles of traditional Chinese medicine changes to improve quality of such preparations--interpretation of Technical guidelines for the study of pharmaceutical changes in traditional Chinese medicines].

In leading the high-quality development of Chinese medicine preparations, it is an important link to formulate the scientific, reasonable, and feasible guidelines for the change of Chinese medicines in accordance with the change characteristics and principles of the Chinese medicines is an important work to promote the Technical guidelines for the study of pharmaceutical changes in traditional Chinese medicines was formed by a broad consensus based on the characteristics and research results of the pharmaceutical changes in Traditional Chinese Medicines(TCM)with the principles of science and risk management. This guideline has clarified the basic principles and requirements for the evaluation of changes in TCM, specified the research and verification work of common change scenarios, defined the boundaries of changes in TCM, and proposed to encourage the use of new technologies, new methods, and new excipients that meet product characteristics. It will definitely promote the quality improvement and the secondary development of TCM. In this article, the revision background and main content of the guideline were introduced, and the main features of the Guideline were analyzed, in order to provide references for the industry.

Dynamic variations of dissolved organic matter from treated wastewater effluent in the receiving water: Photo- and bio-degradation kinetics and its environmental implications.

Dissolved effluent organic matter (dEfOM) from wastewater treatment plants (WWTPs) is bound to encounter photo- and bio-degradation as discharged into the receiving water body. However, the comprehensive variations of dEfOM by photo- and bio-degradation are not well unveiled because of its compositional heterogeneity. In this work, dissolved organic carbon (DOC) concentrations, UV-Vis and fluorescent spectra combined with fluorescence regional integration (FRI) analysis were used to investigate the changes in bulk dEfOM and its fluorescent components during photo- and bio-degradation processes in the receiving water body. Results showed that 48.49%-69.62% of the discharged dEfOM was decomposed by ultra violet (UV)-irradiation and indigenous microbes, while the others (33%-45%) were recalcitrant and stable in the receiving water body. Specifically, the photo- and bio-degradation of chromophoric, fluorescent dEfOM and its components were found to follow the single or double exponential kinetic model, and the differences in photo- and bio-degradability of each components shifted its composition. Furthermore, results of bio-degradation after UV-irradiated dEfOM indicated that there was overlapping of photo- and bio-degradable fractions in dEfOM, and photoreactions could improve the self-production of natural organic matter in the receiving water body. These results could improve the understanding the fate of discharged dEfOM in the receiving water body, and we proposed some cost-effective strategies for discharging WWTPs effluent.

Citrus Naringenin Increases Neuron Survival in Optic Nerve Crush Injury Model by Inhibiting JNK-JUN Pathway.

Traumatic nerve injury activates cell stress pathways, resulting in neuronal death and loss of vital neural functions. To date, there are no available neuroprotectants for the treatment of traumatic neural injuries. Here, we studied three important flavanones of citrus components, in vitro and in vivo, to reveal their roles in inhibiting the JNK (c-Jun N-terminal kinase)-JUN pathway and their neuroprotective effects in the optic nerve crush injury model, a kind of traumatic nerve injury in the central nervous system. Results showed that both neural injury in vivo and cell stress in vitro activated the JNK-JUN pathway and increased JUN phosphorylation. We also demonstrated that naringenin treatment completely inhibited stress-induced JUN phosphorylation in cultured cells, whereas nobiletin and hesperidin only partially inhibited JUN phosphorylation. Neuroprotection studies in optic nerve crush injury mouse models revealed that naringenin treatment increased the survival of retinal ganglion cells after traumatic optic nerve injury, while the other two components had no neuroprotective effect. The neuroprotection effect of naringenin was due to the inhibition of JUN phosphorylation in crush-injured retinal ganglion cells. Therefore, the citrus component naringenin provides neuroprotection through the inhibition of the JNK-JUN pathway by inhibiting JUN phosphorylation, indicating the potential application of citrus chemical components in the clinical therapy of traumatic optic nerve injuries.

Cumulative oxygen deficit is a novel predictor for the timing of invasive mechanical ventilation in COVID-19 patients with respiratory distress.

BACKGROUND AND OBJECTIVES: The timing of invasive mechanical ventilation (IMV) is controversial in COVID-19 patients with acute respiratory hypoxemia. The study aimed to develop a novel predictor called cumulative oxygen deficit (COD) for the risk stratification. METHODS: The study was conducted in four designated hospitals for treating COVID-19 patients in Jingmen, Wuhan, from January to March 2020. COD was defined to account for both the magnitude and duration of hypoxemia. A higher value of COD indicated more oxygen deficit. The predictive performance of COD was calculated in multivariable Cox regression models. RESULTS: A number of 111 patients including 80 in the non-IMV group and 31 in the IMV group were included. Patients with IMV had substantially lower PaO2 (62 (49, 89) vs. 90.5 (68, 125.25) mmHg; p < 0.001), and higher COD (-6.87 (-29.36, 52.38) vs. -231.68 (-1040.78, 119.83) mmHg·day) than patients without IMV. As compared to patients with COD < 0, patients with COD > 30 mmHg·day had higher risk of fatality (HR: 3.79, 95% CI [2.57-16.93]; p = 0.037), and those with COD > 50 mmHg·day were 10 times more likely to die (HR: 10.45, 95% CI [1.28-85.37]; p = 0.029). CONCLUSIONS: The study developed a novel predictor COD which considered both magnitude and duration of hypoxemia, to assist risk stratification of COVID-19 patients with acute respiratory distress.

Linkage between water soluble organic matter and bacterial community in sediment from a shallow, eutrophic lake, Lake Chaohu, China.

Lacustrine sediment played important roles in migration and transformation of its water soluble organic matter (WSOM), and the source and composition of WSOM would affect water trophic status and the fate of pollutants. However, we know little about the pathway of WSOM transformation and its driving bacterial communities in lacustrine sediment. In the present study, we investigated the spatial distribution patterns of sediment WSOM and its fluorescent fractions across Lake Chaohu using fluorescence spectroscopy, and explored WSOM compositional structure through our proposed calculated ratios. In addition, we also analyzed sediment bacterial community using Illumina sequencing technology, and probed the possible pathway of sediment WSOM transformation under the mediate of indigenous bacteria. Our results showed that the inflowing rivers affected the spatial distribution patterns of WSOM and its five fractions (including tyrosine-, tryptophan-, fulvic acid-, humic acid-like substances and soluble microbial productions), and sediment WSOM originated from fresh algae detritus or bacterial sources. In parallel, we also found that Proteobacteria (mainly γ-Proteobacteria and δ-Proteobacteria), Firmicutes (mainly Bacilli), Chloroflexi, Acidobacteria, Planctomycetes and Actinobacteria dominate sediment bacterial community. Furthermore, these dominant bacteria triggered sediment WSOM transformation, specifically, the humic acid-like substances could be converted into fulvic acid-like substances, and further degraded into aromatic protein-like and SMP substances. In addition, our proposed ratios (P-L:H-L, Ar-P:SMP and H-L ratio), as supplementary tool, were effective to reveal WSOM composition structure. These results figured out possible pathway of WSOM transformation, and revealed its microbial mechanism in lacustrine sediment.

Lung Mechanics of Mechanically Ventilated Patients With COVID-19: Analytics With High-Granularity Ventilator Waveform Data.

Background: Lung mechanics during invasive mechanical ventilation (IMV) for both prognostic and therapeutic implications; however, the full trajectory lung mechanics has never been described for novel coronavirus disease 2019 (COVID-19) patients requiring IMV. The study aimed to describe the full trajectory of lung mechanics of mechanically ventilated COVID-19 patients. The clinical and ventilator setting that can influence patient-ventilator asynchrony (PVA) and compliance were explored. Post-extubation spirometry test was performed to assess the pulmonary function after COVID-19 induced ARDS. Methods: This was a retrospective study conducted in a tertiary care hospital. All patients with IMV due to COVID-19 induced ARDS were included. High-granularity ventilator waveforms were analyzed with deep learning algorithm to obtain PVAs. Asynchrony index (AI) was calculated as the number of asynchronous events divided by the number of ventilator cycles and wasted efforts. Mortality was recorded as the vital status on hospital discharge. Results: A total of 3,923,450 respiratory cycles in 2,778 h were analyzed (average: 24 cycles/min) for seven patients. Higher plateau pressure (Coefficient: -0.90; 95% CI: -1.02 to -0.78) and neuromuscular blockades (Coefficient: -6.54; 95% CI: -9.92 to -3.16) were associated with lower AI. Survivors showed increasing compliance over time, whereas non-survivors showed persistently low compliance. Recruitment maneuver was not able to improve lung compliance. Patients were on supine position in 1,422 h (51%), followed by prone positioning (499 h, 18%), left positioning (453 h, 16%), and right positioning (404 h, 15%). As compared with supine positioning, prone positioning was associated with 2.31 ml/cmH2O (95% CI: 1.75 to 2.86; p < 0.001) increase in lung compliance. Spirometry tests showed that pulmonary functions were reduced to one third of the predicted values after extubation. Conclusions: The study for the first time described full trajectory of lung mechanics of patients with COVID-19. The result showed that prone positioning was associated with improved compliance; higher plateau pressure and use of neuromuscular blockades were associated with lower risk of AI.

Combined toxicity of microplastics and cadmium on the zebrafish embryos (Danio rerio).

The effects of microplastics (MPs) on organisms have drawn a worldwide attention in the recent years. In this study, zebrafish embryos were employed to assess the combined effects of MPs and cadmium (Cd) on the aquatic organisms. Lethal and sublethal effects were recorded at 8, 24, 32, 48 and 96 hpe (hour post exposure, hpe). The exposure under a series concentration of MPs and/or an environmental level Cd has the negative impacts on survival and heart rate (HR). And there was a positive correlation between MPs concentration and lethal and sublethal toxicity under combined exposure. The physiological parameters showed that the mixture of two stressors had the antagonistic toxicity under low concentration of MPs (0.05, 0.1 mg/L) while the synergistic sublethal toxicity under high levels of MPs (1, 5, 10 mg/L) on zebrafish embryos. Both the scanning electron micrographs (SEM) and fluorescence microscope photos suggested an electrostatic interaction and weak physical forces generated between MPs and chorion membrane. It is inferred that the 10 µm MPs could induce the protective effect of chorion membrane and cause complex toxicities with Cd. But when it involved with other pollutants, the toxic effects and mechanism are still waiting to be figured out.

Ultra-compact high efficiency and low crosstalk optical interconnection structures based on inverse designed nanophotonic elements.

In this paper, we combine inverse design concept and direct binary search algorithm to demonstrate three ultra-compact high efficiency and low crosstalk on-chip integrated optical interconnection basic devices in the entire wavelength range of 1,400-1600 nm based on silicon-on-insulator platform. A 90-degree waveguide bend with a footprint of only 2.4 × 2.4 µm2 is designed, whose transmission efficiency up to 0.18 dB. A waveguide crossing with a footprint of only 2.4 × 2.4 µm2 is designed, which can provide insertion loss of less than 0.5 dB and crosstalk (CL) of lower than - 19 dB. A same direction waveguide crossing with footprint of only 2.4 × 3.6 µm2 is designed, which can provide the insertion loss of less than 0.56 dB and the crosstalk of lower than - 21 dB. Then, we use them to form several ultra-compact optical interconnect basic structures and performed the simulation calculation. They overall achieve high performance. This will significantly improve the integration density.

Developmental toxicity and transcriptome analysis of 4-epianhydrotetracycline to zebrafish (Danio rerio) embryos.

As a primary degradation by-product of tetracycline (TC), 4-Epianhydrotetracycline (4-EATC) has been detected frequently in the aquatic environment, which may pose a potential environmental risk to aquatic organisms. Up to now, however, the toxicology study on 4-EATC to aquatic organisms is limited. In the present study, in order to better understand the toxic mechanism of 4-EATC, developmental toxicity including lethal and sublethal effects of 4-EATC and TC were investigated. The results showed that the developmental toxicity of 4-EATC to zebrafish embryos was stronger than that of TC. The 96 h LC50 value of 4-EATC to zebrafish embryos was 29.13 mg/L. Malformations seemed to be the most sensitive sublethal endpoint of 4-EATC exposure, and the 96 h EC50 value was 8.57 mg/L. Transcriptome response of 4-EATC to zebrafish embryos was determined. The results showed that 430 different expression genes (DEGs) caused by 4-EATC, and most enriched in tryptophan (TRP) metabolism pathway. Annotation of DEGs in the TRP metabolism demonstrated that expression of 4 gene products in tryptophan metabolized along the kynurenine (KYN) pathway were changed. Disorder of TRP catabolism in KYN pathway was a potential mechanism of 4-EATC toxicity to zebrafish embryos.

Extracorporeal Membrane Oxygenation for SARS-CoV-2 Acute Respiratory Distress Syndrome: A Retrospective Study From Hubei, China.

Background: The data on long-term outcomes of patients infected by SARS-CoV-2 and treated with extracorporeal membrane oxygenation (ECMO) in China are merely available. Methods: A retrospective study included 73 patients infected by SARS-CoV-2 and treated with ECMO in 21 intensive care units in Hubei, China. Data on demographic information, clinical features, laboratory tests, ECMO durations, complications, and living status were collected. Results: The 73 ECMO-treated patients had a median age of 62 (range 33-78) years and 42 (63.6%) were males. Before ECMO initiation, patients had severe respiratory failure on mechanical ventilation with a median PO2/FiO2 of 71.9 [interquartile range (IQR), 58.6-87.0] mmHg and a median PCO2 of 62 [IQR, 43-84] mmHg on arterial blood analyses. The median duration from symptom onset to invasive mechanical ventilation, and to ECMO initiation was19 [IQR, 15-25] days, and 23 [IQR, 19-31] days. Before and after ECMO initiation, the proportions of patients receiving prone position ventilation were 58.9 and 69.9%, respectively. The median duration of ECMO support was 18.5 [IQR 12-30] days. During the treatments with ECMO, major hemorrhages occurred in 31 (42.5%) patients, and oxygenators were replaced in 21 (28.8%) patients. Since ECMO initiation, the 30-day mortality and 60-day mortality were 63.0 and 80.8%, respectively. Conclusions: In Hubei, China, the ECMO-treated patients infected by SARS-CoV-2 were of a broad age range and with severe hypoxemia. The durations of ECMO support, accompanied with increased complications, were relatively long. The long-term mortality in these patients was considerably high.

ß-TrCP-mediated ubiquitination and degradation of Dlg5 regulates hepatocellular carcinoma cell proliferation.

BACKGROUND: Discs large homolog 5 (Dlg5) is a member of the membrane-associated guanylate kinase (MAGUK) adaptor family of proteins and its deregulation has been implicated in the malignancy of several cancer types. Dlg5 was down-regulated in hepatocellular carcinoma (HCC) and lower Dlg5 expression was associated with poor survival of HCC patients. However, how to regulate Dlg5 remains largely unknown. METHODS: The co-immunoprecipitation assay was used to determine the interaction between Dlg5 and ß-TrCP. The in vivo ubiquitination assay was performed to determine the regulation of Dlg5 by ß-TrCP. CCK-8 and colony formation assay were implemented to detect the biological effect of Dlg5 on the growth of HCC cells in vitro. The effect of Dlg5 on HCC tumor growth in vivo was studied in a tumor xenograft model in mice. RESULTS: Here we report that Dlg5 is regulated by the ubiquitin proteasome system and depletion of either Cullin 1 or ß-TrCP led to increased levels of Dlg5. ß-TrCP regulated Dlg5 protein stability by targeting it for ubiquitination and subsequent destruction in a phosphorylation-dependent manner. We further demonstrated a crucial role of Ser730 in the non-canonical phosphodegron of Dlg5 in governing ß-TrCP-mediated Dlg5 degradation. Importantly, failure to degrade Dlg5 significantly inhibited HCC cells proliferation both in vitro and in vivo. CONCLUSION: Collectively, our finding provides a novel molecular mechanism for the negative regulation of Dlg5 by ß-TRCP in HCC cells. It further suggests that preventing Dlg5 degradation could be a possible novel strategy for clinical treatment of HCC.

Dexmedetomidine alleviated lipopolysaccharide/D-galactosamine-induced acute liver injury in mice.

Dexmedetomidine (DEX), a highly selective α2-adrenergic receptor (α2-AR) agonist, is widely used as sedative in clinical. Its potential anti-inflammatory properties have been found in recent studies. The current study has investigated the profound effects of DEX on acute liver injury in mice. The mice were intraperitoneally injected lipopolysaccharide (LPS) and D-galactosamine (D-Gal) to induce acute liver injury, and vehicle or DEX were treated 30 min before or 2 h after LPS/D-Gal exposure. The results showed that pre-treatment with DEX inhibited the raising of plasma aminotransferases, reduced the damage of liver tissue, and improved the survival rate in mice exposed to LPS/D-Gal. Pre-treatment with DEX also inhibited the release of TNF-α and suppressed the phosphorylation of c-jun-N-terminal kinase (JNK) in mice exposed to LPS/D-Gal. In addition, pre-treatment with DEX down-regulated the expression of cleavage of caspase-3, decreased the activities of caspase-3, caspase-8, caspase-9, and consequently, reduced hepatocyte apoptosis. Interestingly, post-treatment with DEX also resulted in beneficial outcomes. The current study indicates that administration of DEX might provide protective benefits in inflammatory liver disease.