ABSTRACT
BACKGROUND: Tuberculosis (TB) is a preventable and curable disease, but mortality remains high among those who develop sepsis and critical illness from TB. METHODS: This was a population-based, multicentre retrospective cohort study of patients admitted to all 15 publicly funded Hong Kong adult intensive care units (ICUs) between 1 April 2008 and 31 March 2019. 940 adult critically ill patients with at least one positive Mycobacterium tuberculosis (MTB) culture were identified out of 133 858 ICU admissions. Generalised linear modelling was used to determine the impact of delay in TB treatment on hospital mortality. Trend of annual Acute Physiology and Chronic Health Evaluation (APACHE) IV-adjusted standardised mortality ratio (SMR) over the 11-year period was analysed by Mann-Kendall's trend test. RESULTS: ICU and hospital mortality were 24.7% (232/940) and 41.1% (386/940), respectively. Of those who died in the ICU, 22.8% (53/232) never received antituberculosis drugs. SMR for ICU patients with TB remained unchanged over the study period (Kendall's τb=0.37, p=0.876). After adjustment for age, Charlson comorbidity index, APACHE IV, albumin, vasopressors, mechanical ventilation and renal replacement therapy, delayed TB treatment was directly associated with hospital mortality. In 302/940 (32.1%) of patients, TB could only be established from MTB cultures alone as Ziehl-Neelsen staining or PCR was either not performed or negative. Among this group, only 31.1% (94/302) had concurrent MTB PCR performed. CONCLUSIONS: Survival of ICU patients with TB has not improved over the last decade and mortality remains high. Delay in TB treatment was associated with higher hospital mortality. Use of MTB PCR may improve diagnostic yield and facilitate early treatment.
Subject(s)
Critical Illness , Tuberculosis , Adult , Humans , Critical Illness/therapy , Retrospective Studies , Intensive Care Units , Hospital Mortality , Treatment OutcomeABSTRACT
Adenosine-to-inosine (A-to-I) RNA editing is the most common posttranscriptional editing to create somatic mutations and increase proteomic diversity. However, the functions of the edited mutations are largely underexplored. To identify novel targets in lung adenocarcinoma (LUAD), we conducted a genome-wide somatic A-to-I RNA editing analysis of 23 paired adjacent normal and LUAD transcriptomes and identified 26,280 events, including known nonsynonymous AZIN1-S367G and novel RHOAiso2 (RHOA isoform 2)-R176G, tubulin gamma complex associated protein 2 (TUBGCP2)-N211S, and RBMXL1-I40 M mutations. We validated the edited mutations in silico in multiple databases and in newly collected LUAD tissue pairs with the SEQUENOM MassARRAY® and TaqMan PCR Systems. We selected RHOAiso2-R176G due to its significant level, isoform-specificity, and being the most common somatic edited nonsynonymous mutation of RHOAiso2 to investigate its roles in LUAD tumorigenesis. RHOAiso2 is a ubiquitous but low-expression alternative spliced isoform received a unique Alu-rich exon at the 3' RHOA mRNA to become an editing RNA target, leading to somatic hypermutation and protein diversity. Interestingly, LUAD patients harboring the RHOAiso2-R176G mutation were associated with aberrant RHOA functions, cancer cell proliferation and migration, and poor clinical outcomes in transcriptome analysis. Mechanistically, RHOAiso2-R176G mutation-expressing LUAD cells potentiate RHOA-guanosine triphosphate (GTP) activity to phosphorylate ROCK1/2 effectors and enhance cell proliferation and migration in vitro and increase tumor growth in xenograft and systemic metastasis models in vivo. Taken together, the RHOAiso2-R176G mutation is a common somatic A-to-I edited mutation of the hypermutated RHOA isoform 2. It is an oncogenic and isoform-specific theranostic target that activates RHOA-GTP/p-ROCK1/2 signaling to promote tumor progression.
Subject(s)
Adenocarcinoma of Lung , Lung Neoplasms , Humans , RNA , Proteomics , Adenosine , Adenocarcinoma of Lung/genetics , Protein Isoforms/genetics , Protein Isoforms/metabolism , Lung Neoplasms/genetics , Guanosine Triphosphate , Inosine , Mutation , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Cell Line, Tumor , rhoA GTP-Binding Protein/genetics , rhoA GTP-Binding Protein/metabolismABSTRACT
A 64 Gb/s four-level pulse amplitude modulation (PAM4) vertical-cavity surface-emitting laser (VCSEL)-based free-space optical (FSO) link with an external light injection scheme is proposed and successfully demonstrated. Experimental results show that the 11.2 GHz VCSEL with an external light injection scheme is sufficiently powerful for 64 Gb/s PAM4 FSO links. This study is the first one that adopts a 1550-nm VCSEL transmitter with an external light injection scheme in a 64 Gb/s PAM4 FSO link. The link performances of the proposed PAM4 VCSEL-based FSO links have been analyzed in real-time in terms of eye diagrams and offline processed by Matlab in terms of bit error rate (BER) performances. Good BER performance and clear eye diagrams are acquired over a 100-m free-space link. Such a proposed 64 Gb/s PAM4 VCSEL-based FSO link with an external light injection scheme is a promising one for providing high transmission rate and long transmission distance.
ABSTRACT
A 16 Gb/s four-level pulse amplitude modulation (PAM4) underwater wireless optical communication (UWOC) system based on 488-nm laser diode (LD) with light injection and optoelectronic feedback techniques is proposed and successfully demonstrated. Experimental results show that such a 1.8-GHz 488-nm blue light LD with light injection and optoelectronic feedback techniques is enough forceful for a 16 Gb/s PAM4 signal underwater link. To the authors' knowledge, this study is the first to successfully adopt a 488-nm LD transmitter with light injection and optoelectronic feedback techniques in a PAM4 UWOC system. By adopting a 488-nm LD transmitter with light injection and optoelectronic feedback techniques, good bit error rate performance (offline processed by Matlab) and clear eye diagrams (measured in real-time) are achieved over a 10-m underwater link. The proposed system has the potential to play a vital role in the future UWOC infrastructure by effectively providing high transmission rate (16 Gb/s) and long underwater transmission distance (10 m).
ABSTRACT
A bidirectional fiber-invisible laser light communication (IVLLC) and fiber-wireless convergence system with two orthogonally polarized optical sidebands for hybrid cable television (CATV)/millimeter-wave (MMW)/baseband (BB) signal transmission is proposed and experimentally demonstrated. Two optical sidebands generated by a 60-GHz MMW signal are orthogonally polarized and separated into different polarizations. These orthogonally polarized optical sidebands are delivered over a 40-km single-mode fiber (SMF) transport to effectually reduce the fiber dispersion induced by a 40-km SMF transmission and the distortion caused by the parallel polarized optical sidebands. To the best of our knowledge, this work is the first to adopt two orthogonally polarized optical sidebands in a bidirectional fiber-IVLLC and fiber-wireless convergence system to reduce fiber dispersion and distortion effectually. Good carrier-to-noise ratio, composite second order, composite triple beat, and bit error rate (BER) are achieved for downlink transmission at a 40-km SMF operation and a 100-m free-space optical (FSO) link/3-m RF wireless transmission. For up-link transmission, good BER performance is acquired over a 40-km SMF transport and a 100-m FSO link. The approach presented in this work signifies the advancements in the convergence of SMF-based backbone and optical/RF wireless-based feeder.
ABSTRACT
A bidirectional fiber-wireless and fiber-invisible laser light communication (IVLLC) integrated system that employs polarization-orthogonal modulation scheme for hybrid cable television (CATV)/microwave (MW)/millimeter-wave (MMW)/baseband (BB) signal transmission is proposed and demonstrated. To our knowledge, it is the first one that adopts a polarization-orthogonal modulation scheme in a bidirectional fiber-wireless and fiber-IVLLC integrated system with hybrid CATV/MW/MMW/BB signal. For downlink transmission, carrier-to-noise ratio (CNR), composite second-order (CSO), composite triple-beat (CTB), and bit error rate (BER) perform well over 40-km single-mode fiber (SMF) and 10-m RF/50-m optical wireless transport scenarios. For uplink transmission, good BER performance is obtained over 40-km SMF and 50-m optical wireless transport scenario. Such a bidirectional fiber-wireless and fiber-IVLLC integrated system for hybrid CATV/MW/MMW/BB signal transmission will be an attractive alternative for providing broadband integrated services, including CATV, Internet, and telecommunication services. It is shown to be a prominent one to present the advancements for the convergence of fiber backbone and RF/optical wireless feeder.
ABSTRACT
Lung cancer is the most common cause of cancer-related mortality with more than 1.4 million deaths per year worldwide. To search for significant somatic alterations in lung cancer, we analyzed, integrated and manually curated various data sets and literatures to present an integrated genomic database of non-small cell lung cancer (IGDB.NSCLC, http://igdb.nsclc.ibms.sinica.edu.tw). We collected data sets derived from hundreds of human NSCLC (lung adenocarcinomas and/or squamous cell carcinomas) to illustrate genomic alterations [chromosomal regions with copy number alterations (CNAs), gain/loss and loss of heterozygosity], aberrant expressed genes and microRNAs, somatic mutations and experimental evidence and clinical information of alterations retrieved from literatures. IGDB.NSCLC provides user friendly interfaces and searching functions to display multiple layers of evidence especially emphasizing on concordant alterations of CNAs with co-localized altered gene expression, aberrant microRNAs expression, somatic mutations or genes with associated clinicopathological features. These significant concordant alterations in NSCLC are graphically or tabularly presented to facilitate and prioritize as the putative cancer targets for pathological and mechanistic studies of lung tumorigenesis and for developing new strategies in clinical interventions.
Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Databases, Genetic , Lung Neoplasms/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , Gene Expression Profiling , Genes, Neoplasm , Genetic Variation , Genomics , Humans , Lung Neoplasms/metabolism , MicroRNAs/metabolism , Mutation , Systems IntegrationABSTRACT
BACKGROUND: and purpose: There is limited evidence from randomised controlled trials (RCTs) regarding the use of yoga and Pilates for the management of urinary incontinence (UI) in women. This study aims to investigate the preliminary effects of using Pilates and yoga to manage UI. MATERIALS AND METHODS: An assessor-blinded, prospective, three-arm parallel-group randomised controlled pilot trial was conducted in three elderly care centres in Hong Kong. Thirty women aged 60 years or above were included in the study. Study centres were randomly assigned to each of the three interventions (yoga, Pilates and pelvic floor muscle training [PFMT; standard care control]). Study interventions were provided once a week for four weeks, followed by unsupervised CD-guided home exercises for eight weeks. Outcomes included the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), 1-h pad test, and feasibility measures such as adherence to the intervention programme, recruitment and retention rates and safety. Outcomes were assessed at baseline, 4 and 12 weeks. Statistical analysis was performed using two-way repeated measures analysis of covariance. RESULTS: All three interventions demonstrated a statistically significant effect on ICIQ-SF scores from baseline to weeks 4 and 12. Significant effects in UI were reported for yoga compared with Pilates (mean: -2.93, 95% CI -5.35, -0.51; p = 0.02). CONCLUSION: Yoga poses intended to address the pelvic floor and core muscles were found to have superior benefits over Pilates exercises in terms of improved continence measured with the ICIQ-SF.
Subject(s)
Urinary Incontinence, Stress , Urinary Incontinence , Yoga , Aged , Exercise Therapy , Female , Humans , Middle Aged , Pelvic Floor , Pilot Projects , Treatment Outcome , Urinary Incontinence/therapyABSTRACT
With the increasing incidence and mortality of human hepatocellular carcinoma (HCC) worldwide, revealing innovative targets to improve therapeutic strategies is crucial for prolonging the lives of patients. To identify innovative targets, we conducted a comprehensive comparative transcriptome analysis of 5,410 human HCCs and 974 mouse liver cancers to identify concordantly expressed genes associated with patient survival. Among the 664 identified prognostic comparative HCC (pcHCC) genes, upregulated pcHCC genes were associated with prognostic clinical features, including large tumor size, vascular invasion and late HCC stages. Interestingly, after validating HCC patient prognoses in multiple independent datasets, we matched the 664 aberrant pcHCC genes with the sorafenib-altered genes in TCGA_LIHC patients and found these 664 pcHCC genes were enriched in sorafenib-related functions, such as downregulated xenobiotic and lipid metabolism and upregulated cell proliferation. Therapeutic agents targeting aberrant pcHCC genes presented divergent molecular mechanisms, including suppression of sorafenib-unrelated oncogenic pathways, induction of sorafenib-unrelated ferroptosis, and modulation of sorafenib transportation and metabolism, to potentiate sorafenib therapeutic effects in HCC combination therapy. Moreover, the pcHCC genes NCAPG and CENPW, which have not been targeted in combination with sorafenib treatment, were knocked down and combined with sorafenib treatment, which reduced HCC cell viability based on disruption to the p38/STAT3 axis, thereby hypersensitizing HCC cells. Together, our results provide important resources and reveal that 664 pcHCC genes represent innovative targets suitable for developing therapeutic strategies in combination with sorafenib based on the divergent synergistic mechanisms for HCC tumor suppression.
ABSTRACT
BACKGROUND: Globally, mortality rates of patients admitted to the intensive care unit (ICU) have decreased over the last two decades. However, evaluations of the temporal trends in the characteristics and outcomes of ICU patients in Asia are limited. The objective of this study was to describe the characteristics and risk adjusted outcomes of all patients admitted to publicly funded ICUs in Hong Kong over a 11-year period. The secondary objective was to validate the predictive performance of Acute Physiology And Chronic Health Evaluation (APACHE) IV for ICU patients in Hong Kong. METHODS: This was an 11-year population-based retrospective study of all patients admitted to adult general (mixed medical-surgical) intensive care units in Hong Kong public hospitals. ICU patients were identified from a population electronic health record database. Prospectively collected APACHE IV data and clinical outcomes were analysed. RESULTS: From 1 April 2008 to 31 March 2019, there were a total of 133,858 adult ICU admissions in Hong Kong public hospitals. During this time, annual ICU admissions increased from 11,267 to 14,068, whilst hospital mortality decreased from 19.7 to 14.3%. The APACHE IV standard mortality ratio (SMR) decreased from 0.81 to 0.65 during the same period. Linear regression demonstrated that APACHE IV SMR changed by - 0.15 (95% CI - 0.18 to - 0.11) per year (Pearson's R = - 0.951, p < 0.001). Observed median ICU length of stay was shorter than that predicted by APACHE IV (1.98 vs. 4.77, p < 0.001). C-statistic for APACHE IV to predict hospital mortality was 0.889 (95% CI 0.887 to 0.891) whilst calibration was limited (Hosmer-Lemeshow test p < 0.001). CONCLUSIONS: Despite relatively modest per capita health expenditure, and a small number of ICU beds per population, Hong Kong consistently provides a high-quality and efficient ICU service. Number of adult ICU admissions has increased, whilst adjusted mortality has decreased over the last decade. Although APACHE IV had good discrimination for hospital mortality, it overestimated hospital mortality of critically ill patients in Hong Kong.
ABSTRACT
Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide due to metastasis. Paraspeckle component 1 (PSPC1) upregulation has been identified as an HCC pro-metastatic activator associated with poor patient prognosis, but with a lack of targeting strategy. Here, we report that PSPC1, a nuclear substrate of PTK6, sequesters PTK6 in the nucleus and loses its metastasis driving capability. Conversely, PSPC1 upregulation or PSPC1-Y523F mutation promotes epithelial-mesenchymal transition, stemness, and metastasis via cytoplasmic translocation of active PTK6 and nuclear translocation of ß-catenin, which interacts with PSPC1 to augment Wnt3a autocrine signaling. The aberrant nucleocytoplasmic shuttling of active PTK6/ß-catenin is reversed by expressing the PSPC1 C-terminal interacting domain (PSPC1-CT131), thereby suppressing PSPC1/PTK6/ß-catenin-activated metastasis to prolong the survival of HCC orthotopic mice. Thus, PSPC1 is the contextual determinant of the oncogenic switch of PTK6/ß-catenin subcellular localizations, and PSPC1-CT131 functions as a dual inhibitor of PSPC1 and PTK6 with potential for improving cancer therapy.
Subject(s)
Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Neoplasm Proteins/metabolism , Protein-Tyrosine Kinases/metabolism , RNA-Binding Proteins/metabolism , beta Catenin/metabolism , Adult , Aged , Animals , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/mortality , Cell Line, Tumor , Cell Nucleus/metabolism , Cytoplasm/metabolism , Disease Progression , Epithelial-Mesenchymal Transition/genetics , Female , Humans , Kaplan-Meier Estimate , Liver/pathology , Liver Neoplasms/genetics , Liver Neoplasms/mortality , Male , Mice , Middle Aged , Mutation , RNA-Binding Proteins/genetics , Signal Transduction , Up-Regulation , Wnt3A Protein/metabolism , Xenograft Model Antitumor Assays , Young AdultABSTRACT
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related mortality because of its poor prognosis. Therefore, identifying targetable genetic mutations and mutational signatures associated with prognosis and treatment strategies are needed. Ultra-deep sequencing of 409 cancer genes using formalin-fixed paraffin-embedded tissue from 33 male patients with hepatitis B virus-associated HCC was performed to identify mutational signatures associated with the prognosis of HCC. A total of 47 genes were found to be mutated in more than 10% of patients. Chromatin remodeling genes were overrepresented in the mutation profile. We found patient survival was associated with mutations in NOTCH1 and the nucleotide excision repair genes which have not been described previously in HCC. From the mutation profile, six patients were eligible for Sorafenib treatment. Among the remaining patients, 7 patients had mutations in genes that are targets for other cancer drugs and 16 patients had mutations in potentially targetable genes. Only one patient carried no potential drug target. We identified mutational signatures associated with the patient survival of HCC. The findings may facilitate identifying subgroups of patients with a poor prognosis as well as potential drug targets for use in personalized strategies for HCC treatment.
ABSTRACT
Targeting tumor angiogenesis is a common strategy against human hepatocellular carcinoma (HCC). However, identification of molecular targets as biomarker for elevating therapeutic efficacy is critical to prolong HCC patient survival. Here, we showed that EIF3C (eukaryotic translation initiation factor 3 subunit C) is upregulated during HCC tumor progression and associated with poor patient survival. Expression of EIF3C did not alter proliferation and expression of other tumor progressive genes such as HIF1A, TGFß1 and VEGF, but reduced cell migration in HCC cells. Nevertheless, expression of EIF3C in HCC cells significantly increase secretion of extracellular exosomes confirmed by increased exosomes labelling by PKH26 fluorescent dye, vesicles in exosome size detected by electronic microscopy and nanoparticle tracking analysis, and expression of divergent exosome markers. The EIF3C-increased exosomes were oncogenic to potentiate tumor angiogenesis via tube formation of HUVEC cells and growth of vessels by plugs assays on nude mice. Subcutaneous inoculation of EIF3C-exosomes mixed with Huh7 HCC cells not only promoted growth of vessels but also increased expression of EIF3C in tumors. Conversely, treatment of exosome inhibitor GW4869 reversed aforementioned oncogenic assays. We identified EIF3C activated expression of S100A11 involved in EIF3C-exosome increased tube formation in angiogenesis. Simultaneous high expression of EIF3C and S100A11 in human HCC tumors for RNA level in TCGA and protein level by IHC are associated with poor survival of HCC patients. Collectively, our results demonstrated that EIF3C overexpression is a potential target of angiogenesis for treatment with exosome inhibitor or S100A11 reduction to suppress HCC angiogenesis and tumorigenesis.
ABSTRACT
Activation of metastatic reprogramming is critical for tumour metastasis. However, more detailed knowledge of the underlying mechanism is needed to enable targeted intervention. Here, we show that paraspeckle component 1 (PSPC1), identified in an aberrant 13q12.11 locus, is upregulated and associated with poor survival in patients with cancer. PSPC1 promotes tumorigenesis, epithelial-to-mesenchymal transition (EMT), stemness and metastasis in multiple cell types and in spontaneous mouse cancer models. PSPC1 is the master activator for transcription factors of EMT and stemness and accompanies c-Myc activation to facilitate tumour growth. PSPC1 increases transforming growth factor-ß1 (TGF-ß1) secretion through an interaction with phosphorylated and nuclear Smad2/3 to potentiate TGF-ß1 autocrine signalling. Moreover, PSPC1 acts as a contextual determinant of the TGF-ß1 pro-metastatic switch to alter Smad2/3 binding preference from tumour-suppressor to pro-metastatic genes. Having validated the PSPC1-Smads-TGF-ß1 axis in various cancers, we conclude that PSPC1 is a master activator of pro-metastatic switches and a potential target for anti-metastasis drugs.
Subject(s)
Autocrine Communication , Cell Movement , Epithelial-Mesenchymal Transition , Neoplasms/metabolism , Neoplastic Stem Cells/metabolism , Nuclear Proteins/metabolism , RNA-Binding Proteins/metabolism , Signal Transduction , Smad2 Protein/metabolism , Smad3 Protein/metabolism , Transforming Growth Factor beta1/metabolism , A549 Cells , Animals , Female , Gene Expression Regulation, Neoplastic , HEK293 Cells , Humans , Male , Mice, Inbred NOD , Mice, Nude , Mice, SCID , Neoplasm Metastasis , Neoplasms/genetics , Neoplasms/pathology , Neoplastic Stem Cells/pathology , Nuclear Proteins/genetics , PC-3 Cells , Phenotype , Phosphorylation , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , RNA-Binding Proteins/genetics , Smad2 Protein/genetics , Smad3 Protein/genetics , Time Factors , Transforming Growth Factor beta1/geneticsABSTRACT
A lab-scale membrane aeration bioreactor (MBR) system was developed for treating synthetic ammonium-rich wastewater to yield an appropriate NO(2)(-)/NH(4)(+) mixture as a pretreatment for anaerobic ammonium oxidation (Anammox). The effluent with a suitable NO(2)(-)/NH(4)(+) ratio (1:1 to 1:1.3) was obtained in 24 h using the developed MBR system under suitable conditions. Additionally, the control of bulk dissolved oxygen (DO) level under a desired condition (anoxic condition) was easier and more economical than traditional aeration systems. An optimal initial alkalinity of 1500 mg CaCO(3)l(-1) was necessary for achieving 50% partial nitrification of wastewater with an initial ammonium concentration of 510 mg NH(4)-N l(-1) within 24 h. Furthermore, there is no need for pH adjustment by adding a base or an acid throughout the reaction if the initial alkalinity is appropriately controlled. Both the appropriate NO(2)(-)/NH(4)(+) ratio and the low DO level make this MBR system an ideal system for Anammox.
Subject(s)
Bacteria, Anaerobic/metabolism , Bioreactors/microbiology , Membranes, Artificial , Nitrates/metabolism , Nitrites/metabolism , Quaternary Ammonium Compounds/metabolism , Water Pollutants, Chemical/metabolism , Industrial Waste/prevention & control , Oxidation-Reduction , Quaternary Ammonium Compounds/isolation & purification , Water Purification/methodsABSTRACT
A gas-permeable silicone membrane bioreactor was used to cultivate the biofilm under hydrogenotrophic condition for reductive dechlorination of 2-chlorophenol (2-CP). The anaerobic sludge obtained from a swine wastewater treatment plant was immobilized by polyvinyl alcohol (PVA) so as to form a biofilm on the surface of the silicone tube. After acclimating for about 4 months, the bioreactor showed a high dechlorinating performance. Under the condition of continuous feeding with 2-CP at 25 mg/l and the hydraulic retention time of 15 h, the 2-CP removal efficiency reached 92.8% (2-CP decay rate: 0.67 g/m(2)d of surface area of silicone tube). H(2) was used as electron donor for dechlorinating 2-CP, and produced the dechlorinating intermediate, phenol. Both nitrate and sulfate played important roles in inhibiting 2-CP dechlorination through different biological mechanisms. Nitrate can be easily utilized as an electron acceptor by the biofilm, while sulfate cannot. Results of this study demonstrated that nitrate competed with 2-CP as the electron acceptor, while sulfate retarded the activity of hydrogen-dechlorinating bacteria and thus inhibited the 2-CP dechlorination.
Subject(s)
Biofilms , Bioreactors , Chlorophenols/metabolism , Membranes, Artificial , Water Purification/methods , Kinetics , Nitrates/metabolism , Permeability , Polyvinyl Alcohol/metabolism , Sewage/microbiology , Silicones/chemistry , Sulfates/metabolismABSTRACT
This research studies the 2-chlorophenol (2-CP) degradation by the hydrogenotrophic biofilm cultivated in three silicone-tube membrane bioreactors under the conditions of denitrification (DN), sulfate-reduction (DS) and dechlorination (DC). Experimental results showed that after acclimation for more than four months with 2-CP, the respective 2-CP removal efficiency was 95% in DN, 94% in DS and 95% in DC reactors, under the condition of influent 2-CP 25 mg/l with hydraulic retention time (HRT) of 15 h. The metabolic pathway of 2-CP was different in different reactors. The 2-CP was thought to be utilized as carbon and energy source in DN and DS reactors, while the dechlorination occurred in the DC reactor in lack of nitrate and sulfate. The pH dramatically affected the 2-CP degradation in all reactors. Experimental results showed that the optimal pH range was around 6+/-0.2 in DN, 7+/-0.2 in DS, and 5.8-7.2 in DC reactors. Both nitrate and sulfate inhibited the 2-CP dechlorination, but the inhibition levels were different. Nitrate completely inhibited the dechlorination at once, while sulfate took a longer time to reach complete inhibition, only after the bacteria were adapted to the sulfate-reducing condition. Both inhibitions were accomplished by taking the place of 2-CP as electron acceptors. H2 served as an electron donor for dechlorination of 2-CP. The dechlorination was apparently stopped when lacking H2 and another pathway was responsible for the 2-CP degradation.
Subject(s)
Biofilms , Bioreactors , Chlorophenols/metabolism , Hydrogen/metabolism , Water Pollutants, Chemical/metabolism , Chlorine/chemistry , Chromatography, High Pressure Liquid , Hydrogen-Ion Concentration , Sulfates/chemistry , Time FactorsABSTRACT
PURPOSE: Histone deacetylase inhibitors (HDACi) are actively explored as new-generation epigenetic drugs but have low efficacy in cancer monotherapy. To reveal new mechanism for combination therapy, we show that HDACi induce cell death but simultaneously activate tumor-progressive genes to ruin therapeutic efficacy. Combined treatments to target tumorigenesis and HDACi-activated metastasis with low toxic modalities could develop new strategies for long-term cancer therapy. EXPERIMENTAL DESIGN: Because metastasis is the major cause of cancer mortality, we measured cell migration activity and profiled metastasis-related gene expressions in HDACi-treated cancer cells. We developed low toxic combination modalities targeting tumorigenesis and HDACi-activated metastasis for preclinical therapies in mice. RESULTS: We showed that cell migration activity was dramatically and dose dependently enhanced by various classes of HDACi treatments in 13 of 30 examined human breast, gastric, liver, and lung cancer cell lines. Tumor metastasis was also enhanced in HDACi-treated mice. HDACi treatments activated multiple PKCs and downstream substrates along with upregulated proapoptotic p21. For targeting tumorigenesis and metastasis with immediate clinical impact, we showed that new modalities of HDACi combined drugs with PKC inhibitory agent, curcumin or tamoxifen, not only suppressed HDACi-activated tumor progressive proteins and cell migration in vitro but also inhibited tumor growth and metastasis in vivo. CONCLUSION: Treatments of different structural classes of HDACi simultaneously induced cell death and promoted cell migration and metastasis in multiple cancer cell types. Suppression of HDACi-induced PKCs leads to development of low toxic and long-term therapeutic strategies to potentially treat cancer as a chronic disease.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cell Movement/drug effects , Histone Deacetylase Inhibitors/administration & dosage , Neoplasms/drug therapy , Animals , Cell Line, Tumor , Cell Survival/drug effects , Cell Transformation, Neoplastic/drug effects , Combined Modality Therapy , Curcumin/administration & dosage , Gene Expression Regulation, Neoplastic/drug effects , Humans , Hydroxamic Acids/administration & dosage , Matrix Metalloproteinase Inhibitors/administration & dosage , Matrix Metalloproteinases/metabolism , Mice , Neoplasm Metastasis , Neoplasms/metabolism , Neoplasms/pathology , Protein Kinase C/antagonists & inhibitors , Protein Kinase C/metabolism , Tamoxifen/administration & dosageABSTRACT
The feasibility of an anaerobic ammonium oxidation (anammox) process combined with a cell-immobilization technique for autotrophic nitrogen removal was investigated. Anammox biomass was cultivated from local activated sludge and achieved significant anammox activity in 6 months. The development of a mature anammox biomass was confirmed by fluorescence in situ hybridization (FISH) analysis and off-line activity measurements. The abundance fraction of the anammox bacteria determined by FISH analysis was estimated by software. The anaerobic ammonia oxidizers occupied almost half of the total cells. Additionally, the anammox biomass was granulated as spherical gel beads of 3-4 mm in diameter by using a cell-immobilization technique. The nitrogen removal activity was proved to be successfully retained in the beads, with about 80% of nitrogenous compounds (NH(4) (+), NO(2) (- )and total nitrogen) removed after 48 h. These results offer a promising technique for the preservation of anammox microorganisms, the protection of them against the unfavorable surroundings, and the prevention of biomass washout towards the implementation of sustainable nitrogen elimination biotechnology. This is the first report on the immobilization of anammox biomass as gel beads.