Maladaptation of host-microbiota metabolic interplay plays a critical role in colorectal cancer initiation. Here, through a combination of single-cell transcriptomics, microbiome profiling, ...metabonomics, and clinical analysis on colorectal adenoma and carcinoma tissues, we demonstrate that host’s urea cycle metabolism is significantly activated during colorectal tumorigenesis, accompanied by the absence of beneficial bacteria with ureolytic capacity, such as Bifidobacterium, and the overabundance of pathogenic bacteria lacking ureolytic function. Urea could enter into macrophages, inhibit the binding efficiency of p-STAT1 to SAT1 promotor region, and further skew macrophages toward a pro-tumoral phenotype characterized by the accumulation of polyamines. Treating a murine model using urea cycle inhibitors or Bifidobacterium-based supplements could mitigate urea-mediated tumorigenesis. Collectively, this study highlights the utility of urea cycle inhibitors or therapeutically manipulating microbial composition using probiotics to prevent colorectal cancer.
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•Urea cycle is activated through colorectal adenoma-to-carcinoma sequence•Urea cycle activation depends on the absence of gut microbes with ureolytic capacity•Overabundant intestinal urea is a driving force for colorectal cancer initiation•Urea skews macrophages toward a pro-tumoral phenotype through the accumulation of polyamines
Chen et al. report that host’s urea cycle metabolism is activated during colorectal carcinogenesis, accompanied by the absence of gut microbes with ureolytic capacity, represented by Bifidobacterium, and the overabundance of pathogenic bacteria that lack ureolytic function. Urea can skew macrophages toward a pro-tumoral phenotype characterized by the accumulation of polyamines.
The application of blue laser lithography for creating antireflective submicron structures on a crystalline silicon substrate was evaluated. The assembled blue laser lithography system was obtained ...by modifying a commercial blue laser optical pickup head and consisting of a 405-nm-wavelength blue laser and a 0.85-numerical-aperture objective lens. Si substrates were patterned with submicron column patterns of various periods and aspect ratios by blue laser lithography using a sputtered Ge-Sb-Sn-O layer as a resist. The reflectance of the patterned Si substrate decreased to 3% on average in the 300–1000 nm wavelength range, with a low sensitivity to the angle of incident light. Such patterned substrates showed potential for application in crystalline Si solar cells.
Aircraft maintenance is an integral component of an aviation system. 21% of all reported incidents in the Aviation Safety Reporting System (ASRS) are fatigue-related, and 18% of all accidents have ...maintenance factors involved. Guidelines for Maintenance Resource Management (MRM) are hence developed to combine human factors knowledge with interpersonal skills and personal maintenance skills in order to improve communication effectiveness and safety in aircraft maintenance operations. One of the identified human factors that lead to maintenance errors is fatigue. This paper examined the psychological and physiological fatigue variation in shift workers and the subjective factors affecting the fatigue of line maintenance crews. Questionnaires collected from two major airlines in Taiwan are used to investigate the underlying fatigue factors.
Based on the analysis results, several suggestions are provided to airlines to further improve line maintenance crews' work mood and fatigue.
•Fatigue related data of maintenance crews of two major airlines in Taiwan are sampled and analyzed.•Four major factors that affect maintenance crews' fatigue variation are identified.•Fatigue variations of different work shifts are analyzed and discussed.•Suggestions are provided to airlines to improve line maintenance crews' fatigue.
Carcinoma of unknown origin has a poor outcome and usually occurs in elderly patients. In this article, we analyzed the prognostic factors in elderly patients with cancer of unknown primary site ...(CUP) for treatment considerations.
Patients >70 years old with histologically proven carcinoma were retrospectively reviewed. The prognostic factors were analyzed with univariate and multivariate Cox regression.
We included 63 patients aged 70-79 years and 51 patients ≥80 years old. The results of multivariate Cox regression in the 70-79 years age group revealed white blood cell count ≤10(4)/ml p = 0.033; hazard ratio (HR) 2.51, range 1.079-5.840 and albumin ≥3.5 g/dl (p = 0.007; HR 3.38, range 1.398-8.177) as independent factors. In the group of patients ≥80 years old, Eastern Cooperative Oncology Group performance status <1 (p = 0.020), white blood cell count ≤10(4)/ml (p = 0.001), albumin ≥3.5 g/dl (p = 0.006), lactate dehydrogenase (LDH) ≤250 U/l (p = 0.002) and non-chest metastasis (p = 0.043) were significantly better with univariate analysis. Multivariate Cox regression revealed albumin ≥3.5 g/dl (p = 0.007; HR 3.28, range 1.389-7.745) and LDH ≤250 U/l (p = 0.045; HR 3.18, range 1.026-9.848) as independent factors.
For elderly patients with CUP, the serum albumin level seems to be a consistently independent prognostic factor. In patients >80 years old, serum LDH plays an important role in prognosis. This study is helpful in predicting the outcome and management for this group of patients.
In Taiwan, lung cancers occur predominantly in never-smokers, of whom nearly 60% have stage IV disease at diagnosis. We aimed to assess the efficacy of low-dose CT (LDCT) screening among ...never-smokers, who had other risk factors for lung cancer.
The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) was a nationwide, multicentre, prospective cohort study done at 17 tertiary medical centres in Taiwan. Eligible individuals had negative chest radiography, were aged 55-75 years, had never smoked or had smoked fewer than 10 pack-years and stopped smoking for more than 15 years (self-report), and had one of the following risk factors: a family history of lung cancer; passive smoke exposure; a history of pulmonary tuberculosis or chronic obstructive pulmonary disorders; a cooking index of 110 or higher; or cooking without using ventilation. Eligible participants underwent LDCT at baseline, then annually for 2 years, and then every 2 years up to 6 years thereafter, with follow-up assessments at each LDCT scan (ie, total follow-up of 8 years). A positive scan was defined as a solid or part-solid nodule larger than 6 mm in mean diameter or a pure ground-glass nodule larger than 5 mm in mean diameter. Lung cancer was diagnosed through invasive procedures, such as image-guided aspiration or biopsy or surgery. Here, we report the results of 1-year follow-up after LDCT screening at baseline. The primary outcome was lung cancer detection rate. The p value for detection rates was estimated by the χ
test. Univariate and multivariable logistic regression analyses were used to assess the association between lung cancer incidence and each risk factor. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of LDCT screening were also assessed. This study is registered with ClinicalTrials.gov, NCT02611570, and is ongoing.
Between Dec 1, 2015, and July 31, 2019, 12 011 participants (8868 females) were enrolled, of whom 6009 had a family history of lung cancer. Among 12 011 LDCT scans done at baseline, 2094 (17·4%) were positive. Lung cancer was diagnosed in 318 (2·6%) of 12 011 participants (257 2·1% participants had invasive lung cancer and 61 0·5% had adenocarcinomas in situ). 317 of 318 participants had adenocarcinoma and 246 (77·4%) of 318 had stage I disease. The prevalence of invasive lung cancer was higher among participants with a family history of lung cancer (161 2·7% of 6009 participants) than in those without (96 1·6% of 6002 participants). In participants with a family history of lung cancer, the detection rate of invasive lung cancer increased significantly with age, whereas the detection rate of adenocarcinoma in situ remained stable. In multivariable analysis, female sex, a family history of lung cancer, and age older than 60 years were associated with an increased risk of lung cancer and invasive lung cancer; passive smoke exposure, cumulative exposure to cooking, cooking without ventilation, and a previous history of chronic lung diseases were not associated with lung cancer, even after stratification by family history of lung cancer. In participants with a family history of lung cancer, the higher the number of first-degree relatives affected, the higher the risk of lung cancer; participants whose mother or sibling had lung cancer were also at an increased risk. A positive LDCT scan had 92·1% sensitivity, 84·6% specificity, a PPV of 14·0%, and a NPV of 99·7% for lung cancer diagnosis.
TALENT had a high invasive lung cancer detection rate at 1 year after baseline LDCT scan. Overdiagnosis could have occurred, especially in participants diagnosed with adenocarcinoma in situ. In individuals who do not smoke, our findings suggest that a family history of lung cancer among first-degree relatives significantly increases the risk of lung cancer as well as the rate of invasive lung cancer with increasing age. Further research on risk factors for lung cancer in this population is needed, particularly for those without a family history of lung cancer.
Ministry of Health and Welfare of Taiwan.
Lower serum low-density lipoprotein cholesterol (LDL-C) levels are associated with increased intracerebral hemorrhage (ICH) risk. However, reverse causality and residual confounding has not attracted ...public attention. Therefore, we assessed whether people with LDL-C have increased risk of mortality adjusting for potential confounders using two large Taiwan cohorts.
The Mei-Jhao (MJ) cohort has 414,372 adults participating in a medical screening program with 378 ICH deaths within 15 years of follow-up (1994-2008). Cox proportional hazards regressions estimated hazard death ratios according to LDL-C levels. We identified 4,606 ICH patients from the Taiwan Stroke Registry (TSR) and analyzed the impact of LDL-C on 3-month mortality.
Low cholesterol (LDL-C <100 mg/dL), found in 1/4 of the MJ cohort, was highly prevalent (36%) among young adults (age 20-39). There was a graded relationship between cholesterol and mortality for ICH Hazard ratio, 1.56; 95% confidence interval (CI), 1.13-2.16. Compared with patients with an LDL-C of 110-129 mg/dL in TSR, the risk for mortality was 1.84 (95% CI, 1.28-2.63) with an LDL-C of <100 mg/dL.
Lower serum LDL-C level independently predicts higher mortality after acute ICH. While its causative role may vary, low cholesterol may pose potential harms in Taiwan.
We performed an integrated cytogenetic study using a combination of comparative genomic hybridization (CGH), spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) to analyze ...chromosomal aberrations associated with 8 human esophageal squamous cell carcinoma (EC-SCC) cell lines, and used real-time quantitative PCR (Q-PCR) to study the copy number changes of two candidate genes of chromosome 3q, PIK3CA and TP63, in 20 primary tumors of EC-SCC. The pooled CGH results revealed frequent gain abnormalities on chromosome arms 1p, 1q, 3q, 5p, 6p, 7p, 7q, 8q, 9q, 11q, 12p, 14q, 15q, 16p, 16q, 17q, 18p, 19q, 20q, 22q, and Xq, while frequent losses were found on 3p, 4, 5q, 6q, 7q, 9p, and 18q. SKY detected 195 translocations, 13 deletions and 2 duplications. Among the 374 breakpoints, most clustered at the centromeric regions, such as 8q10, 13q10, 7q10, 9q10, 14q10, 15q10, 16q10, 21q10, and 22q10, but also at other regions, including 3q (3q21, 3q22, 3q25), 7p (7p22, 7p14, 7p12), 7q (7q21, 7q31, 7q32), 8q (8q21.1, 8q23), 11q (11q21, 11q24), 13q (13q14) and 18q (18q21). There was a good correlation between the number of aberrations identified by CGH and SKY (r=0.667; p=0.035). Combined CGH and SKY analyses indicated that chromosomes 3, 7, 9, 11, 14, 16, 18, 19, 20, and 22 harbored higher frequency of chromosomal aberrations than expected. FISH using BAC clones containing oncogene PIK3CA and TP63 found that both genes were amplified in 6 and 5 cell lines, respectively. Q-PCR analysis of primary tumors revealed amplification of PIK3CA and TP63 in 100% and 80% of the cases. Average copy number of PIK3CA per haploid genome was greater than that of TP63 (6.27 vs 2.73), and the difference showed statistical significance (p<0.001). Combination of CGH, SKY and FISH could reveal detailed chromosomal changes associated with esophageal cancer cells, and Q-PCR could assess the change of the candidate genes in clinical samples in a high throughput way.
Programmers depend on virtual platforms, such as Android-QEMU, to build and test their applications as well as system software for the ease of development efforts. It is easy to add tracing modules ...to the virtual platforms to dump the execution trace of the guest system, which can then be used to estimate and evaluate the performance of alternative system designs. However, tracing in virtual platforms are performed at the architecture level, which makes it difficult to generate traces for specific applications due to the lack of high-level software information. This problem becomes even more challenging for Android systems, which use component-based design strategies, where applications request services from other components. In this paper, we propose a novel Android-QEMU tracing system, which follows the invocations among the service components, generates component-service-aware traces only for specific applications. The evaluation results show that the proposed system improves 152% in simulation time and saves 33% of storage space in average compared to the static QEMU-Tracer.
The aim of this study was to analyze the host responses to ionizing radiation by nuclear factor-kappaB (NF-kappaB) bioluminescence imaging-guided transcriptomic tool. Transgenic mice carrying the ...NF-kappaB-driven luciferase gene were exposed to a single dose of 8.5 Gy total-body irradiation. In vivo imaging showed that a maximal NF-kappaB-dependent bioluminescent intensity was observed at 3 h after irradiation and ex vivo imaging showed that liver, intestine, and brain displayed strong NF-kappaB activations. Microarray analysis of these organs showed that irradiation altered gene expression signatures in an organ-specific manner and several pathways associated with metabolism and immune system were significantly altered. Additionally, the upregulation of fatty acid binding protein 4, serum amyloid A2, and serum amyloid A3 genes, which participate in both inflammation and lipid metabolism, suggested that irradiation might affect the cross pathways of metabolism and inflammation. Moreover, the alteration of chemokine (CC-motif) ligand 5, chemokine (CC-motif) ligand 20, and Jagged 1 genes, which are involved in the inflammation and enterocyte proliferation, suggested that these genes might be involved in the radiation enteropathy. In conclusion, this report describes the comprehensive evaluation of host responses to ionizing radiation. Our findings provide the fundamental information about the in vivo NF-kappaB activity and transcriptomic pattern after irradiation. Moreover, novel targets involved in radiation injury are also suggested.
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