Determining the prevalence of Escherichia coli, Salmonella, and shiga toxin-producing Escherichia coli in manure of dairy lagoons.

AIM: The aim of this study was to determine the prevalence of microbial pathogens in manure of dairy lagoons in California. METHODS AND RESULTS: To determine pathogens in dairy manure stored in anaerobic lagoons of dairy farm, an extensive field study was conducted across California to sample manure from 20 dairy farms. Samples were analyzed to determine the prevalence of indicator E. coli, Shiga toxin producing E. coli (STEC), Salmonella, and E. coli O157:H7. To test the E. coli, STEC, and Salmonella, we used agar culture-based method followed by polymerase chain reaction (PCR) method. In addition, a real- time PCR based method was used to determine the presence of E coli O157:H7. Study demonstrated that the prevalence of Salmonella in manure sample is lower than E. coli. The presence of Salmonella was found in 2.26% of the samples, and both the culture-based and PCR methods yielded comparable outcomes in detecting Salmonella. Moreover, approximately 11.30% of the total samples out of the 177 were identified as positive for STEC by qPCR. CONCLUSION: These findings demonstrate that indicator E. coli are abundantly present in anaerobic lagoons. However, the presence of STEC, and Salmonella is substantially low.

Economic and environmental performance of microalgal energy products - A case study exploring circular bioeconomy principles applied to recycled anaerobic digester waste flows.

This study quantifies the financial and environmental impacts of a microalgal bioenergy system that attempts to maximize circular flows by recovering and reusing the carbon, nutrients, and water within the system. The system produces microalgal biomass using liquid digestate of an anaerobic digester that processes 45 metric tons of food waste and generates 28.6 m3 of permeate daily in California, and three energy production scenarios from the biomass are considered: producing biodiesel, electricity, and both. In all scenarios, the resulting energy products delivered only modest reductions in environmental impacts as measured by carbon dioxide equivalent emissions. The carbon intensities (CIs) of biodiesel from this study were 91.0 gCO2e/MJ and 93.3 gCO2e/MJ, which were lower than 94.71 gCO2e/MJ of conventional petroleum diesel, and the CI of electricity from this study was 70.6 gCO2e/MJ, lower than the average electricity grid CI in California (82.92 gCO2e/MJ). The economic analysis results show that generating electricity alone can be profitable, while biodiesel produced via this system is not cost competitive with conventional diesel due to high capital expenses. Thus, generating electricity in lieu of biodiesel appears to be a better option to maximize the use of waste flows and supply lower-carbon energy.

Effects of photoperiod on the growth and physiological responses in Ulva prolifera under constant and diurnal temperature difference conditions.

Photoperiod and temperature are two main factors in the growth of macroalgae, and changes in photoperiod and diurnal temperature difference exist in natural condition. In order to study the effects of photoperiod and diurnal temperature difference on the growth of green algae Ulva prolifera, we cultured this species under three light/dark cycles (light: dark = 10:14, 12:12 and 16:08) with constant (22 °C for light and dark period, noted as 22-22 °C) and diurnal temperature difference (22 °C and 16 °C for light and dark period, respectively, noted as 22-16 °C) conditions. The results showed that: 1) Compared with 10:14 light/dark cycle, the growth of U. prolifera under 12:12 light/dark cycle was significantly enhanced by 39% and 16% for 22-22 °C and 22-16 °C treatments, respectively, while the increase proportion decreased when the daylength increase from 12 h to 16 h. 2) The enhancement in growth induced by diurnal temperature difference was observed under 10:14 light/dark cycle, but not for 12:12 and 16:08 light/dark cycle treatments. 3) The Chl a content and photosynthetic rate increased under short light period and 22-22 °C conditions, while under 22-16 °C conditions, higher photosynthetic rate was observed under 12:12 light/dark cycle and no significant difference in Chl a content was observed. 4) Under 22-22 °C conditions, compared with 10:14 (L:D) treatment, the expression levels of proteins in light-harvesting complexes, PSII and carbon fixation were down regulated, while the photorespiration and pentose phosphate pathway (PPP) were up regulated by 16:08 light dark cycle. Then we speculate that the higher photosynthetic rate may be one compensation mechanism in short photoperiod, and under long light period condition the up regulations of photorespiration and PPP can be in charge of the decrease in enhancement growth induced by longer daylength.

[Retracted] Clinical significance of miR­1298 in cervical cancer and its biological function in vitro.

[This retracts the article DOI: 10.3892/ol.2021.12662.].

Prospective observational study on biomarkers of response in pancreatic ductal adenocarcinoma.

Adjuvant chemotherapy benefits patients with resected pancreatic ductal adenocarcinoma (PDAC), but the compromised physical state of post-operative patients can hinder compliance. Biomarkers that identify candidates for prompt adjuvant therapy are needed. In this prospective observational study, 1,171 patients with PDAC who underwent pancreatectomy were enrolled and extensively followed-up. Proteomic profiling of 191 patient samples unveiled clinically relevant functional protein modules. A proteomics-level prognostic risk model was established for PDAC, with its utility further validated using a publicly available external cohort. More importantly, through an interaction effect regression analysis leveraging both clinical and proteomic datasets, we discovered two biomarkers (NDUFB8 and CEMIP2), indicative of the overall sensitivity of patients with PDAC to adjuvant chemotherapy. The biomarkers were validated through immunohistochemistry on an internal cohort of 386 patients. Rigorous validation extended to two external multicentic cohorts-a French multicentric cohort (230 patients) and a cohort from two grade-A tertiary hospitals in China (466 patients)-enhancing the robustness and generalizability of our findings. Moreover, experimental validation through functional assays was conducted on PDAC cell lines and patient-derived organoids. In summary, our cohort-scale integration of clinical and proteomic data demonstrates the potential of proteomics-guided prognosis and biomarker-aided adjuvant chemotherapy for PDAC.

Down-regulated Wnt7a and GPR124 in early-onset preeclampsia placentas reduce invasion and migration of trophoblast cells.

OBJECTIVES: Preeclampsia (PE) is a disease specific to pregnancy that causes 9-10 % of maternal deaths. Early-onset PE (<34 weeks' gestation) is the most dangerous category of PE. Wnt7a and GPR124 (G protein-coupled receptor 124) are widely expressed in the human reproductive process. Especially during embryogenesis and tumorigenesis, Wnt7a plays a crucial role. However, few studies have examined the association between Wnt7a-GPR124 and early-onset PE. The aim of this study was to examine the significance of Wnt7a and GPR124 in early-onset PE as well as Wnt7a's role in trophoblast cells. METHODS: Immunohistochemistry (IHC), real-time PCR, and western blotting (WB) were used to investigate Wnt7a and GPR124 expression in normal and early-onset PE placentas. Additionally, FACS, Transwell, and CCK-8 assays were used to diagnose Wnt7a involvement in migration, invasion, and proliferation. RESULTS: In the early-onset PE group, Wnt7a and GPR124 expression was significantly lower than in the normal group, especially in the area of syncytiotrophoblasts (STBs) and extravillous trophoblasts (EVTs). A negative correlation was found between Wnt7a RNA and GPR124 expression (r=-0.42, p<0.01). However, the Wnt7a RNA expression level was positive correlated with PE severity. In further cellular functional experiments, knockdown of Wnt7a inhibits HTR8/SVeno cells invasion and migration but has little effect on proliferation and apoptosis. CONCLUSIONS: Through the Wnt pathway, Wnt7a regulates trophoblast cell invasion and migration, and may contribute to early-onset preeclampsia pathogenesis. A molecular level study of Wnt7a will be needed to find downstream proteins and mechanisms of interaction.

Training and practice of wound ostomy continence nurse specialists in China.

BACKGROUND: In China, with chronic wound patients increasing by 10% per year and more than 1 million stoma patients, there is an increasing demand for wound ostomy continence care. Accordingly, specialized wound care in China is developing rapidly and the gap with developed countries is narrowing. PURPOSE: This paper aims to describe the status of training, practice, and management of wound nurses in China. METHODS: Data on the training and practice of wound specialist nurses in the Chinese Mainland were collected through literature review and hospital surveys. RESULTS: The training system of Chinese Wound, Ostomy and Continence (WOC) specialist nurses is developing rapidly, but lacks a unified access standard, curriculum, teaching materials, and assessment system. Specialist nurses play an important role in education, clinical practice, and scientific research, but home care and independent nursing practices are still in their infancy. CONCLUSION: The developing momentum of wound care in China is encouraging, but it is necessary to unify and standardize WOC nurses' qualification certification, scope of practice, level-to-level administration, and other aspects to cultivate higher-quality specialized wound nurses.

TRIM21-mediated Sohlh2 ubiquitination suppresses M2 macrophage polarization and progression of triple-negative breast cancer.

Lung metastasis is the major cause of death in patients with triple-negative breast cancer (TNBC). Tumor-associated macrophages (TAMs) represent the M2-like phenotype with potent immunosuppressive activity, and play a pro-tumor role in TNBC lung metastasis. Sohlh2 belongs to the basic helix-loop-helix transcription factor family. However, its role in macrophages polarization remains unknown, especially in TNBC progression. Here we demonstrated that Sohlh2 overexpression promoted M2 macrophage polarization. Moreover, high expression of Sohlh2 in M2-like macrophage enhanced TNBC cell growth, migration and lung metastasis in vivo and in vitro. Mechanistically, we revealed that Sohlh2 functioned through up-regulating LXRα, ABCA1, ABCG1 expression and disturbing the lipid homeostasis on the membrane of macrophages. Sohlh2 could directly bind to the promoter of LXRα and promote its transcription activity. E3 ubiquitin ligase TRIM21 promoted Sohlh2 ubiquitination and degradation, and suppressed M2 macrophage polarization and TNBC progression. Collectively, our findings suggested that Sohlh2 in macrophage could be a novel therapeutic target for TNBC metastatic treatment.

Cross-sectional network analysis of plasma proteins/metabolites correlated with pathogenesis and therapeutic response in acute promyelocytic leukemia.

The treatment of PML/RARA+ acute promyelocytic leukemia (APL) with all-trans-retinoic acid and arsenic trioxide (ATRA/ATO) has been recognized as a model for translational medicine research. Though an altered microenvironment is a general cancer hallmark, how APL blasts shape their plasma composition is poorly understood. Here, we reported a cross-sectional correlation network to interpret multilayered datasets on clinical parameters, proteomes, and metabolomes of paired plasma samples from patients with APL before or after ATRA/ATO induction therapy. Our study revealed the two prominent features of the APL plasma, suggesting a possible involvement of APL blasts in modulating plasma composition. One was characterized by altered secretory protein and metabolite profiles correlating with heightened proliferation and energy consumption in APL blasts, and the other featured APL plasma-enriched proteins or enzymes catalyzing plasma-altered metabolites that were potential trans-regulatory targets of PML/RARA. Furthermore, results indicated heightened interferon-gamma signaling characterizing a tumor-suppressing function of the immune system at the first hematological complete remission stage, which likely resulted from therapy-induced cell death or senescence and ensuing supraphysiological levels of intracellular proteins. Overall, our work sheds new light on the pathophysiology and treatment of APL and provides an information-rich reference data cohort for the exploratory and translational study of leukemia microenvironment.

Sohlh2 promotes pulmonary fibrosis via repression of p62/Keap1/Nrf2 mediated anti-oxidative signaling pathway.

Disturbance in the redox balance of alveolar epithelial cells (AECs) was considered as a causal factor for pulmonary fibrosis. The regulatory mechanisms of redox hemostasis in the development of pulmonary fibrosis remain largely unknown. Using a type II AEC-specific Sohlh2 conditional knock-in (CKI) mouse model, we found that Sohlh2, a basic HLH transcription factor, accelerated age-related pulmonary fibrosis. High-fat diet (HFD) resulted in a tremendous increase in lung inflammation and fibrotic changes in the lung tissues of Sohlh2 CKI mice. Sohlh2 overexpression led to a significant rise of intracellular ROS and apoptosis in the lung, mouse primary AECIIs, and human A549 cells, which was attenuated by ROS inhibitor (NAC). Sohlh2 enhanced oxidative stress via repressing p62/Keap1/Nrf2 mediated anti-oxidative signaling pathway. p62, a direct target of Sohlh2, mediated Sohlh2 effects on ROS generation and apoptosis in A549 cells. Hence, our findings elucidate a pivotal mechanism underlying oxidative stress-induced pulmonary fibrosis, providing a framework for aging-related disorder interventions.

GPCR signaling contributes to immune characteristics of microenvironment and process of EBV-induced lymphomagenesis.

Epstein-Barr virus (EBV) is the oncogenic driver of multiple cancers. However, the underlying mechanism of virus-cancer immunological interaction during disease pathogenesis remains largely elusive. Here we reported the first comprehensive proteogenomic characterization of natural killer/T-cell lymphoma (NKTCL), a representative disease model to study EBV-induced lymphomagenesis, incorporating genomic, transcriptomic, and in-depth proteomic data. Our multi-omics analysis of NKTCL revealed that EBV gene pattern correlated with immune-related oncogenic signaling. Single-cell transcriptome further delineated the tumor microenvironment as immune-inflamed, -deficient, and -desert phenotypes, in association with different setpoints of cancer-immunity cycle. EBV interacted with transcriptional factors to provoke GPCR interactome (GPCRome) reprogramming. Enhanced expression of chemokine receptor-1 (CCR1) on malignant and immunosuppressive cells modulated virus-cancer interaction on microenvironment. Therapeutic targeting CCR1 showed promising efficacy with EBV eradication, T-cell activation, and lymphoma cell killing in NKTCL organoid. Collectively, our study identified a previously unknown GPCR-mediated malignant progression and translated sensors of viral molecules into EBV-specific anti-cancer therapeutics.

Systemic immune profiling of Omicron-infected subjects inoculated with different doses of inactivated virus vaccine.

SARS-CoV-2 primary strain-based vaccination exerts a protective effect against Omicron variants-initiated infection, symptom occurrence, and disease severity in a booster-dependent manner. Yet, the underlying mechanisms remain unclear. During the 2022 Omicron outbreak in Shanghai, we enrolled 122 infected adults and 50 uninfected controls who had been unvaccinated or vaccinated with two or three doses of COVID-19 inactive vaccines and performed integrative analysis of 41-plex CyTOF, RNA-seq, and Olink on their peripheral blood samples. The frequencies of HLA-DRhi classical monocytes, non-classical monocytes, and Th1-like Tem tended to increase, whereas the frequency of Treg was reduced by booster vaccine, and they influenced symptom occurrence in a vaccine dose-dependent manner. Intercorrelation and mechanistic analysis suggested that the booster vaccination induced monocytic training, which would prime monocytic activation and maturation rather than differentiating into myeloid-derived suppressive cells upon Omicron infections. Overall, our study provides insights into how booster vaccination elaborates protective immunity across SARS-CoV-2 variants.

Sharp angular and unidirectional filter based on accidental degeneracy between two twisted Weyl semimetal-based defect modes in a one-dimensional photonic crystal.

To address the challenges associated with the realization of optical non-reciprocity and enhance the efficiency of GaAs solar cells, among other systems, in this study, we investigated defect-mode interactions in a one-dimensional photonic crystal containing two Weyl semimetal-based defect layers. Moreover, two non-reciprocal defect modes were observed, namely, when defects are identical and nearby. Increasing the defect distance weakened the defect-mode interactions, thus causing the modes to gradually move closer and then degenerate into one mode. It should be noted that by changing the optical thickness of one of the defect layers, the mode was found to degrade to two non-reciprocal dots with different frequencies and angles. This phenomenon can be attributed to an accidental degeneracy of two defect modes with dispersion curves that intersect in the forward and backward directions, respectively. Moreover, by twisting Weyl semimetal layers, the accidental degeneracy occurred only in the backward direction, thus resulting in a sharp angular and unidirectional filter.

Dingkun Pill modulate ovarian function in chemotherapy-induced premature ovarian insufficiency mice by regulating PTEN/PI3K/AKT/FOXO3a signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Dingkun Pill (DKP) is a traditional Chinese medicine that has been shown to have beneficial effects on reproductive function. However, the specific mechanism underlying its effect on POI is not well understood. AIM OF THE STUDY: To investigate the effect of different doses of Dingkun Pill on ovarian function in cyclophosphamide (CTX)-induced premature ovarian insufficiency (POI) mice and to explore its molecular mechanism through PTEN/PI3K/AKT/FOXO3a signaling pathway. This study will provide valuable insights into the potential clinical application of Dingkun Pill for the treatment of POI. MATERIALS AND METHODS: Fifty female ICR mice were randomly divided into normal control (NC) group, model control (MC) group, and Dingkun Pill low, medium, high dose (DKP-L, M, H) groups. Mice were injected with CTX to construct the POI model. Mice in the DKP-L, M, and H groups were given 0.9 g/kg, 1.8 g/kg, and 3.6 g/kg of Dingkun Pill suspension for 21 days, respectively. Mice in the NC and MC groups were given the same amount of normal saline by gavage. Changes in body weight, estrous cycle and gonadal index were observed in each group of mice. Serum levels of FSH, LH, E2 and AMH were detected by ELISA. Hematoxylin-eosin (HE) staining observed the changes of ovarian pathological morphology and follicle counts at all levels. qRT-PCR was used to measure the levels of the PTEN and FOXO3a genes in ovarian tissue. The expression of PTEN/PI3K/AKT/FOXO3a signaling pathway related proteins were detected by Western-blot and immunohistochemistry (IHC). RESULTS: In POI mice, Dingkun Pill increased body weight, promoted the recovery of estrous cycle, increased ovarian index, and improved pathological morphology of the ovaries. The FSH level decreased in the medium dose group (P < 0.05), the LH level reduced significantly in the medium and high dose groups (P < 0.01), and the E2 level in the high dose group increased (P < 0.05). There was no significant difference in AMH levels across all dose groups. The number of growing follicles improved at all levels in the low and medium dose groups, but declined significantly in the high dose group. However, the number of corpus luteum increased significantly in the high dose group (P < 0.001), and the atretic follicles in the three dose groups decreased. Results from qRT-PCR, Western-blot and IHC showed that the moderate dose of Dingkun Pill suppressed the levels of the p-PI3K and p-AKT proteins by upregulating the expression of PTEN in the ovarian tissues of POI mice, thereby inhibiting the expression of the key protein p-FOXO3a. However, the inhibitory effect of the higher dose may be less than that of the lower and intermediate dose groups. CONCLUSIONS: The Dingkun Pill modulated hormonal levels, promoted follicle growth and induced ovulation in mice with CTX-induced POI, with better results in the low and moderate dose groups. Its mechanism may be related to the regulation of the PTEN/PI3K/AKT/FOXO3a signaling pathway.

Nematode-Suppressive Potential of Digestates to Meloidogyne incognita and Heterodera schachtii.

Management of plant-parasitic nematodes uses host plant resistance, crop rotation, cultural methods, and nematicide applications. Host plant resistance is tedious to develop, and crop rotation and cultural methods are challenging to use. Environmental and human health concerns render sole reliance on chemical nematode suppression nonsustainable. Previously, digestate from anaerobically fermented maize silage suppressed Heterodera schachtii in Beta vulgaris crops. Here, seven digestates were investigated for nematode suppressive potential: liquid dairy manure digestate (LDMD), liquid dairy manure digestate with ammonia removed (LDMDA-), food waste digestate (FWD), liquid food waste digestate with ammonia removed (LFWDA-), liquid food waste digestate (LFWD), food waste hydrolysate from the Renewable Energy Anaerobic Digester (HREAD), and food waste hydrolysate from the South Area Transfer Station in Sacramento (HSATS). In a red radish (Raphanus sativus) bioassay with H. schachtii, digestates were amended at rates of 0.02, 0.11, 0.57, and 2.86 ml per 100 cm3 of soil. At a rate of 2.86 ml, all amendments except LDMDA- and LFWDA- significantly reduced juvenile root penetration compared with the infested control. In a greenhouse watermelon (Citrullus lanatus) bioassay with Meloidogyne incognita, amendments FWD, LFWD, HREAD, and HSATS as well as LDMD (less effectively) at 2.86 and 5.76 ml per 100 cm3 of soil significantly reduced egg masses per root system compared with the nontreated, nematode-infested control. In a microplot experiment with M. incognita and red radish, in the treatment amended with LFWD at 2.37 ml per 100 cm3 of soil, marketable yields were improved by approximately 50% over the nontreated control and were comparable with those in the treatment with the nematicide Reklemel. In a second microplot experiment with M. incognita and watermelon, treatments that contained LFWD at rates of 3.55 ml per 100 cm3 of soil had transient numerical effects of initial nematode suppression that were not maintained throughout the 3-month growth period. The results of these studies demonstrated that digestates FWD and LFWD consistently expressed some nematode-suppressive capacity.

A Sensitive LC-MS/MS Method for the Simultaneous Determination of Skimmin, a Potential Agent for Treating Postpartum Stroke, and Its Metabolite Umbelliferone in Rat Plasma.

BACKGROUND: Skimmin, a potential agent for treating postpartum stroke, is one of the most important coumarins extracted from the leaves of skimmia. OBJECTIVE: In this study, a specific, sensitive, and simple high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method for the simultaneous determination of skimmin and its metabolite umbelliferone in rat plasma was established and validated. METHOD: Chromatographic separation was performed by an Inertsil ODS-3 column (50 mm × 4.6 mm, 5 µm) with a mobile phase consisting of 0.1% formic acid in distilled water-acetonitrile at a flow rate of 0.5 mL/min with gradient elution mode. All analytes were detected and quantified in negative multiple reaction monitoring (MRM). RESULTS: All calibration curves showed good linearity (r > 0.995) over the concentration range of 10-10 000 and 2.0-2000 ng/mL for skimmin and umbelliferone, respectively. The selectivity, sensitivity, extraction recovery, matrix effect, and stability met all requirements. CONCLUSIONS: The analysis method was successfully applied to the pharmacokinetic study of skimmin and umbelliferone in rats following oral administration of skimmin at the doses of 10, 30, and 90 mg/kg. With the exception of AUC(0-∞) and Cmax, MRT and Cl/F of skimmin had significant statistical difference with the increasing doses. Skimmin might exhibit nonlinear pharmacokinetic characteristics in rats. HIGHLIGHTS: This was the first study to investigate the pharmacokinetic characteristics of skimmin as a candidate agent for treating postpartum stroke.

Sohlh2 Regulates the Stemness and Differentiation of Colon Cancer Stem Cells by Downregulating LncRNA-H19 Transcription.

Colon cancer stem cells (CSC) are tumor-initiating cells that drive tumorigenesis and progression through self-renewal and various differentiation potency. Therefore, the identification of factors critical for colon CSC function is vital for the development of therapies. Sohlh2 belongs to the superfamily of bhlh transcription factors and serves as a tumor suppressor in several tumors. The role of Sohlh2 in CSCs remains unknown. Here we demonstrated that Sohlh2 was related to the inhibition of LncRNA-H19/miR-141/ß-catenin signaling and led to the consequent suppression of colon CSC stemness and the promotion of colon CSC differentiation in vitro and in vivo. Moreover, Sohlh2 could directly bind to the promoter of LncRNA-H19 and repress its transcription activity. LncRNA-H19 mediated the effects of Sohlh2 on colon CSC stemness and differentiation. Clinically, we observed a significant inverse correlation between Sohlh2 and LncRNA-H19, ß-catenin, Lgr5, CD133 expression levels, and positive correlation between Sohlh2 and MUC2, TFF2 expression in colon cancer tissues. Collectively, our findings suggest an important role of the Sohlh2/LncRNA-H19/miR-141/ß-catenin pathway in regulating colon CSC stemness and differentiation, suggesting potential therapeutic targets for colon cancer. IMPLICATIONS: This study identifies that Sohlh2 directly manipulates LncRNA-H19 transcription and suppresses the ß-catenin signaling pathway and the Sohlh2/LncRNA-H19/miR-141/ß-catenin signaling pathway plays an essential role in the stemness of colon CSCs.

Identification of eIF6 as a prognostic factor that drives tumor progression and predicts arsenic trioxide efficacy in lung adenocarcinoma.

BACKGROUND: Lung cancer is the leading cause of cancer-related mortality worldwide. Dysregulation of mRNA translation can contribute to the development and progression of cancer whilst also having an impact on the prognosis of different types of malignancies. Eukaryotic translation initiation factors (eIFs) have been reported to serve a key role in the initiation of mRNA translation. However, little was known about the association between eIF6 and lung adenocarcinoma (LUAD) progression. We aimed to elucidate the roles of eIF6 in LUAD tumorigenesis. METHODS: Bioinformatic analysis was conducted to assess the clinical significance of eIF6 in LUAD. CCK-8, colony formation assays were used to evaluate the biological roles of eIF6. The subcutaneous model was used to assess the in vivo roles of eIF6. RESULTS: In the present study, it was found that eIF6 expression was significantly higher in LUAD samples compared with that in normal lung tissues. Higher expression levels of eIF6 were found to be associated with more advanced clinical stages of LUAD and poorer prognoses in patients with LUAD. Subsequently, overexpression of eIF6 was demonstrated to promote LUAD cell proliferation, migration and invasion, which are features of metastasis, in vitro. By contrast, inhibition of eIF6 induced cell cycle arrest and apoptosis in LUAD cells. Further bioinformatics analysis and experimental assays revealed that eIF6 expression positively correlated with the mRNA expression of stemness-associated genes in LUAD cells. Targeting eIF6 suppressed the sphere formation capacity of LUAD cells. In addition, data from the subcutaneous xenograft model in vivo also suggested that eIF6 deficiency could significantly delay tumor growth and improve the prognosis of mice. Targeting eIF6 rendered LUAD cells sensitive to arsenic trioxide treatment. CONCLUSION: The present study suggest that eIF6 can serve as a prognostic biomarker and a potential therapeutic target for patients with LUAD.

Immobilization of Diatom Phaeodactylum tricornutum with Filamentous Fungi and Its Kinetics.

Immobilizing microalgae cells in a hyphal matrix can simplify harvest while producing novel mycoalgae products with potential food, feed, biomaterial, and renewable energy applications; however, limited quantitative information to describe the process and its applicability under various conditions leads to difficulties in comparing across studies and scaling-up. Here, we demonstrate the immobilization of both active and heat-deactivated marine diatom Phaeodactylum tricornutum (UTEX 466) using different loadings of fungal pellets (Aspergillus sp.) and model the process through kinetics and equilibrium models. Active P. tricornutum cells were not required for the fungal-assisted immobilization process and the fungal isolate was able to immobilize more than its original mass of microalgae. The Freundlich isotherm model adequately described the equilibrium immobilization characteristics and indicated increased normalized algae immobilization (g algae removed/g fungi loaded) under low fungal pellet loadings. The kinetics of algae immobilization by the fungal pellets were found to be adequately modeled using both a pseudo-second order model and a model previously developed for fungal-assisted algae immobilization. These results provide new insights into the behavior and potential applications of fungal-assisted algae immobilization.

AKAP8L enhances the stemness and chemoresistance of gastric cancer cells by stabilizing SCD1 mRNA.

Gastric cancer (GC) remains the third leading cause of cancer-related deaths. Chemoresistance is the major determinant of GC treatment failure. To explore the molecular mechanisms of GC chemoresistance, mass spectrometry was performed to detect the genes altered in expression between chemoresistant and chemosensitive GC. PRKA kinase anchor protein 8L (AKAP-8L) was identified as one of the top upregulated genes in chemoresistant GC tissues. Moreover, the higher AKAP-8L expression was associated with the lower survival rate in GC patients. Overexpression of AKAP-8L enhanced the GC cell stemness and chemoresistance of oxaliplatin in vivo and in vitro. AKAP-8L deficiency obtained the opposite results. Mechanistically, AKAP-8L interacted with Stearoyl-CoA desaturase 1 (SCD1) mRNA and IGF2BP1 protein, and regulated SCD1 mRNA stability via IGF2BP1-dependent manner. SCD1 played a critical role in mediating the function of AKAP-8L in GC cell stemness and chemoresistance. Clinically, AKAP-8L and SCD1 protein levels was positively associated with human GC chemoresistance. Taken together, our results demonstrated that AKAP-8L facilitates GC chemoresistance via regulating SCD1-mediated stemness of GC cells. AKAP8L may represent a novel therapeutic target to overcome GC chemoresistance.