Colorectal cancer can be prevented if detected early (e.g., precancerous polyps‐adenoma). Endoscopic differential diagnosis of hyperplastic polyps (that have little or no risk of malignant transformation) and adenomas (that have prominent malignant latency) remains an unambiguous clinical challenge. Raman spectroscopy is an optical vibrational technique capable of probing biomolecular changes of tissue associated with neoplastic transformation. This work aims to apply a fiber‐optic simultaneous fingerprint (FP) and high wavenumber (HW) Raman spectroscopy technique for real‐time in vivo assessment of adenomatous polyps during clinical colonoscopy. We have developed a fiber‐optic Raman endoscopic technique capable of simultaneously acquiring both the FP (i.e., 800–1800 cm–1) and HW (i.e., 2800–3600 cm–1) Raman spectra from colorectal tissue subsurface (<200 µm) for real‐time assessment of colorectal carcinogenesis. In vivo FP/HW Raman spectra were acquired from 50 patients with 17 colorectal polyps during clinical colonoscopy. Prominent Raman spectral differences (p < 0.001) were found between hyperplastic (n = 118 spectra), adenoma (n = 184 spectra) that could be attributed to changes in inter‐ and intra‐cellular proteins, lipids, DNA and water structures and conformations. Simultaneous FP/HW Raman endoscopy provides a diagnostic sensitivity of 90.9% and specificity of 83.3% for differentiating adenoma from hyperplastic polyps, which is superior to either the FP or HW Raman technique alone. This study shows that simultaneous FP/HW Raman spectroscopy technique has the potential to be a clinically powerful tool for improving early diagnosis of adenomatous polyps in vivo during colonoscopic examination.
There are quite a few ongoing biochemical investigations of nicotine degradation in different organisms. In this work, we identified and sequenced a gene (designated nicA) involved in nicotine degradation by Pseudomonas putida strain S16. The gene product, NicA, was heterologously expressed and characterized as a nicotine oxidoreductase catalyzing the initial steps of nicotine metabolism. Biochemical analyses using resting cells and the purified enzyme suggested that nicA encodes an oxidoreductase, which converts nicotine to 3-succinoylpyridine through pseudooxynicotine. Based on enzymatic reactions and direct evidence obtained using H218O labeling, the process may consist of enzyme-catalyzed dehydrogenation, followed by spontaneous hydrolysis and then repetition of the dehydrogenation and hydrolysis steps. Sequence comparisons revealed that the gene showed 40% similarity to genes encoding NADH dehydrogenase subunit I and cytochrome c oxidase subunit I in eukaryotes. Our findings demonstrate that the molecular mechanism for nicotine degradation in strain S16 involves the pyrrolidine pathway and is similar to the mechanism in mammals, in which pseudooxynicotine, the direct precursor of a potent tobacco-specific lung carcinogen, is produced. 相似文献
OBJECTIVEs: Bone remodeling has recently been revealed to be under sympathetic nerve control. The role of the sympathetic nerve system is not clearly understood. The present study aim to explore the effect of chemical sympathectomy and stress on bone remodeling in adult rats. METHODS: 24 twelve-month-old Wistar rats were divided into three group (sympathectomy, stress and control). The sympathectomy and stress group rats were administered 6-hydroxydopamine (150?mg/kg each day) and saline (1?ml/kg each day) intraperitoneal respectively for one week and exposed to stress procedure for another three weeks. The stress procedure was mild, unpredictable footshock, administered for one hour once daily. Analysis of serum chemistry, microcomputed tomography, dual energy X-ray absorptiometry, biomechanical testing and bone histomorphometry were employed. RESULTS: The stress group rats showed increased bone resorption in contrast to the sympathectomy and control group rats. The serum level of calcium and phosphorus cations and norepinephrine were enhanced, the cancellous bone volume and bone mineral density were reduced, bone mechanical property such as strength, ductility and toughness were weakened, the osteoclast counts and osteoclast surfaces were increased and the bone formatin rate were decreased significantly in the stress group rats in contrast to the other two groups rats. There was no significant difference of bone remodeling between the sympathectomy group and control group rats. CONCULSION: Our study showed stress-increased sympathetic nerve system activity enhanced bone resorption while chemical sympathectomy inhibited bone resorption under stress. We postulate sympathetic neurotransmitter and neuropepitide may play a role in regulating bone remodeling. 相似文献
A quantitative two-parameter model is developed to describe local energy minima distribution. On a conformational space measured by least-square-fitting root-mean-squared distance (RMSD), the number of local minima in a r RMSD region is proposed to be proportional to exp(-1/r). As part of the model derivations, the minimum RMSD of decoys from the largest cluster, the number of decoys in the largest cluster, and the RMSD distribution of the decoys have inner connections with each other. The model is successfully verified on a 49 helix-packing decoy set and a 30 loop-prediction decoy set, as well as both knowledge-based potential (DFIRE) and physical force-fields (OPLS and CHARMM). One of the model's applications is predicting behaviors of a large amount of decoys (e.g., minimum RMSD of 40,000 decoys) by generating only a small number of decoys (e.g., 500). It may be applied to structure predictions guided by any Lennard-Jones-like potential functions and can be extended to other sampling methods guided by simple energy terms. 相似文献