Associations between Sedentary Duration and Cognitive Function in Older Adults: A Longitudinal Study with 2-Year Follow-Up.

OBJECTIVES: This study aimed to investigate the association between different forms of sedentary behavior and cognitive function in Chinese community-dwelling older adults. DESIGN: A longitudinal study with a 2-year follow-up. SETTING AND PARTICIPANTS: Data from 5356 participants at baseline and 956 participants at the follow-up of the Anhui Healthy Longevity Survey (AHLS) were analysed. MEASUREMENTS: Cognitive function was evaluated by the Mini-Mental State Examination (MMSE), and mild cognitive impairment (MCI) was classified according to education-specific criteria. Self-report questionnaires were used to assess the sedentary behavior of the participants. RESULTS: The participants who reported longer screen-watching sedentary duration had higher MMSE scores (1-2 hours: ß=0.758, 95% CI: 0.450, 1.066; > 2 hours: ß=1.240, 95% CI: 0.917, 1.562) and lower likelihoods of MCI (1-2 hours: OR= 0.787, 95% CI: 0.677, 0.914; >2 hours: OR=0.617, 95% CI: 0.524, 0.726). The participants who had played cards (or mahjong) sedentary had higher MMSE scores (ß= 1.132, 95% CI: 0.788, 1.476) and lower likelihoods of MCI (OR=0.572, 95% CI: 0.476, 0.687). However, the participants who reported longer other forms of sedentary duration had lower MMSE scores (1-2 hours: ß=-0.409, 95% CI: -0.735, -0.082; > 2 hours: ß=-1.391, 95% CI: -1.696, -1.087) and higher likelihoods of MCI (1-2 hours: OR=1.271, 95% CI: 1.081, 1.496; > 2 hours: OR=1.632, 95% CI: 1.409, 1.889). No significant association was detected between sedentary duration and MCI incidence. CONCLUSION: Variations in the impact of diverse sedentary behaviors on the cognitive function were detected in Chinese older adults. However, such associations were cross-sectional and longitudinal associations were not found in the current study.

Upgrade of vacuum ultraviolet spectroscopy system on J-TEXT tokamak.

The vacuum ultraviolet (VUV) spectroscopy system on the Joint Texas Experimental Tokamak has been upgraded to achieve fast acquisition for the study of impurity transport in transient modulated experiments. In this upgrade, the previous high-energy charge-coupled device detector was replaced by a microchannel plate with a CsI-coated photocathode and P43 phosphor to transform the VUV light to visible light, which is then acquired by a high-speed electron-multiplying charge-coupled device. Two-stage focusing was achieved using a reference slit plate illuminated successively by a green light source and the Lyman series hydrogen spectral lines from the vacuum-conditioning plasma. The spatial resolution was evaluated as ∼4 mm based on the level of image blurring from the alignment plate. A response time of ∼2 ms was obtained with the ten-vertical-track setup.

[The cervical microbiota characteristics in patients with human papillomavirus infection].

Objective: To investigate the characteristics of cervical microbiota in patients with HPV (Human Papillomavirus) infection, and to analyze the associations of cervical microbiota and HPV infection or cervicitis. Methods: 300 samples underwent HPV nucleic acid testing was collected in this case-control study from June 2019 to April 2020 in the Zhujiang Hospital of Southern Medical University, there were 150 cases allocated in HPV infection group (HPV+), and 150 cases of negative nucleic acid test were non-infectious Group (HPV-). Next-generation sequencing was used to sequence the V4 region of the bacterial 16S rRNA gene, and QIIME pipeline was used to analysis the microbiota composition of the two groups. Wilcoxon rank sum test and Kruskal-Wallis test were used to statistically analysis the differences of the microbiota between groups; and the α diversity and ß diversity of the flora between groups were statistically analyzed by Adonis multivariate analysis of variance and Wilcoxon rank sum test. Results: A total of 300 samples were analyzed in this study, of which 150 samples were HPV-positive and 150 samples were HPV-negative; among HPV-positive cases, 132 were infected by high-risk HPV (88.0%), and 18 were low-risk HPV infections (12.0%). The composition of the cervical microbiota were significantly different between the HPV+group and the HPV-group, which in the HPV+group, the α diversity of the cervical microbiota were significantly increased (Shannon index, W=8 174, P<0.000 1; PD whole tree, W=8 887, P=0.001 7). The ß diversity of the two groups was significantly different (Binary Jaccard, F=2.325 4, P=0.042 0; Bray Curtis, F=2.136 44, P=0.044 0). The relative abundance of Lactobacillus spp. and L.iners in the HPV+group sample decreased significantly (W=7 730, P<0.000 1; W=8 979, P=0.002 5), accompanied by enriched Achromobacter, Stenotrophomonas, Methylobacterium, Sneathia and Dialister. There was no significant difference in the composition of the cervical microbiota between high-risk HPV infection and low-risk HPV infection (F=4.100 4, P>0.05). In addition, cervicitis is significantly related to HPV infection (χ²=19.78, P<0.000 1), the composition of cervical flora has similarity features in cervicitis and HPV infection samples. Compared with the normal group, the cervical microbiota of cervicitis with HPV infection is mainly enriched in Achromobacter, Aerococcaceae, Streptococcus, Fusobacteria, and Xanthomonadaceae. Conclusion: The cervical microbiota of patients with HPV infection has a significant dysbiosis, with increased diversity and significant depletion of lactobacillus, accompanied by an increase in the abundance of pathogenic bacteria such as Achromobacter.

Losartan prevents bladder fibrosis and protects renal function in rat with neurogenic paralysis bladder.

AIMS: To investigate the effect of losartan on preventing bladder fibrosis and protecting renal function in rats with neurogenic paralysis bladder (NPB). MATERIALS AND METHODS: Rats were assigned to the transecting spinal nerves group (TSNG), transecting spinal nerves + losartan group (LSTG), and control group (CG). On Day 32 postsurgery, bladder capacity (BC), bladder compliance (ΔC), bladder leakage pressure (Pves.leak ) of TSNG and LSTG while BC, ΔC, and bladder threshold pressure (Pves.thre ) of CG were measured by cystometry in each cohort. Renal function and the expression quantity of Angiotensin Ⅱ (Ang II) in blood were detected, in addition Ang II, Ang II Type 1 receptor (AT1), transformation growth factor ß1 (TGFß1), Collagen Ⅲ, and collagen fibrin in the bladder tissue were detected too. RESULTS: ΔC in TSNG and LSTG decreased significantly compared to the CG. Pves.leak in TSNG and LSTG were significantly higher than Pves.thre in CG. Renal function of both TSNG and LSTG decreased significantly compared with the CG, but renal function in LSTG was better than in TSNG. Ang Ⅱ in blood and bladder tissue in TSNG and LSTG increased significantly compared with CG. AT1 was expressed in the bladder tissue of all rats. The TGFß1, Collagen Ⅲ, and collagen fibrin expression level increased significantly in TSNG compared with LSTG and CG, while these levels were not significantly different between CG and LSTG. CONCLUSION: Losartan might prevent NPB fibrosis by stopping the upregulated signaling of Ang II/AT1/TGFß1 and consequently may reduce kidney damage from occurring.

[Status of content analysis of pyrrolizidine alkaloids in food and herbs].

Pyrrolizidine alkaloids(PAs) are a group of naturally occurring alkaloids with a pyrrolizidine skeleton which can be found in about 3% of the world's flowering plants. It is notorious that PAs are cause the hepatoxic and genotoxic-carcinogenic effects by taking PA-containing herbs, food and dietary supplements. In order to control the poisoning caused by PAs, European Medicines Agency has set a limit of intake of PAs from herbal medicinal products at 0.007 µg of 1,2-unsaturated PAs/kg body weight. Nonetheless, a systematic overview of the amount of PAs in the herb has not been provided. Therefore, this paper is to systematically review the current status of PAs content analysis of herbal medicines and foods reported in the literature, and to provide theoretical and experimental support for the safety risk assessment and control of PAs in Chinese herbal medicines.

[Preparation of compound liquorice microemulsion gel and its pharmacodynamics evaluation].

Based on the previous study of compound liquorice microemulsion, this paper aims to prepare the compound liquorice microemulsion gel and investigate its pharmacodynamics of chronic eczema. The type, dosage and adding method of gel matrix, and formula dosage of humectant were optimized by single factor method to obtain the formula and preparation technique of the gel. With glycyrrhizic acid, glycyrrhetin and oxymatrine used as evaluation indexes, the Franz diffusion cell method was adopted to monitor the in vitro release profile of the gel. Eczema model of delayed-type hypersensitivity in mice was chosen to detect the ear swelling rate, degree of inflammatory cell infiltration of ear pieces, and pathological changes of ear pieces, so as to investigate the therapeutic effect of the microemulsion gel. The preparation process of the compound liquorice microemulsion gel was stable. The release of glycyrrhizin and oxymatrine was most consistent with the Hixcon-Crowell kinetic model, while the release of glycyrrhizic acid was most consistent with the Ritger-Peppas kinetic model. The pharmacodynamics studies proved that compound liquorice microemulsion gel could significantly reduce the ear swelling rate in mice, with good anti-inflammatory effect as well as the ability to resist the pathological changes of chronic eczema and inhibit the infiltration of dermal inflammatory cells. Therefore, the preparation process of compound liquorice microemulsion gel is feasible, with stable drug release and a significant therapeutic effect on chronic eczema.

[Establishment of concentration process and physical property parameter model of Carthami Flos extract based on quality by design].

To explore the potential of "physical property model" based on the concept of quality by design(QbD),during the application of process analysis technology(PAT) in the concentration process. The Carthami Flos was used as a model drug. Firstly, the total flavonoid retention rate and the hydroxysafflor yellow A(HSYA) retention rate of the concentrated solution were used as indicators to determine the concentration temperature range of the Carthami Flos extract. Then different concentrations were prepared at the optimal concentration temperature, and the corresponding viscosity(η) and electrical conductivity(σ) at different concentrations and temperatures were measured. Data processing software such as Excel, 1 stOpt, SPSS, and MATLAB were used to establish Carthami Flos extract's mathematical model of physical parameters: ρ-C, η-C, η-T, η-C-T, σ-T, σ-C-T. The results showed that the best concentration temperature of the Carthami Flos extract should not exceed 60 ℃, and the R~2 of the exponential equation and Arrhenius equation established based on physical parameters was all greater than 0.9, indicating that such model had better predictive ability. The mathematical model:η=14.465 1 exp(-0.019 8T+ 0.771 1C-0.058 3C~2), σ=4.061 0 + 0.004 3T +(-1.104 1 +0.950 9T)C-0.556 9TC~2 can be used to reflect the comprehensive effect of concentration and temperature on viscosity or conductance, laying foundation for the establishment of an online monitoring system for the viscosity or conductivity of the extraction liquid in the concentration step, rapid prediction of the concentration status, and control of the concentration endpoint. This study has initially proved the feasibility of using the physical property model as the core of the research idea in application of PAT for intelligent quality control of traditional Chinese medicine concentration links, providing a reference for the online intelligent monitoring of concentration steps of traditional Chinese medicine extracts.

Inhibition of Sumoylation Alleviates Oxidative Stress-induced Retinal Pigment Epithelial Cell Senescence and Represses Proinflammatory Gene Expression.

PURPOSE: Advanced age is the largest risk factor for age-related macular degeneration (AMD). Sumoylation is a reversible post-translational modification that conjugates small peptide, small ubiquitin-like modifier (SUMO), to a target protein. Dysregulation of sumoylation is recently found to be critically involved in several age-related disorders. However, the effects of sumoylation during retina senescence and aging remains elusive. This study is aimed to investigate the function and regulation of sumoylation pathway in the aging retina and premature senescent retinal pigment epithelial (RPE) cells. METHODS: 1.5- and 10-month C57/B6 mice were used for comparative aging study. Both ARPE primary cultures and ARPE-19 cells were used for assay systems. The qRT-PCR was used for analysis of mRNA expression. Western blot and immunofluorescence were used to analyze the protein expression. Cell flow cytometry was used for cell cycle progression analysis. RPE barrier function and senescent-associated ß-galactosidase (SA ß-gal) activity were analyzed to measure cellular senescence. RESULTS: We show that the expression of SUMO enzymes and global protein sumoylation were downregulated in the aging mouse retina, and in the oxidative stress (OS) -induced premature senescent RPE cells. Dramatical altered distribution of SUMO E1, E2 and E3 enzymes were observed during RPE senescence. Inhibition of sumoylation alleviated OS-induced cell senescence in RPE cells, as indicated by decreased p21 and p53 expression and decreased percentage of cell cycle arrest at G0/G1 phase. Intriguingly, inhibition of SUMO E1 repressed the expression of proinflammatory cytokine and chemokine in the premature senescent RPE cells. However, inhibition of sumoylation did not prevent DNA damage during the OS-induced RPE senescence process. CONCLUSIONS: Our data indicate sumoylation critically regulates retina and RPE aging and that targeting sumoylation process may provide potential therapeutic strategy for AMD treatment.

SUMOylation in Neurological Diseases.

Since the discovery of SUMOs (small ubiquitin-like modifiers) over 20 years ago, sumoylation has recently emerged as an important posttranslational modification involved in almost all aspects of cellular physiology. In neurons, sumoylation dynamically modulates protein function and consequently plays an important role in neuronal maturation, synapse formation and plasticity. Thus, the dysfunction of sumoylation pathway is associated with many different neurological disorders. Hundreds of different proteins implicated in the pathogenesis of neurological disorders are SUMO-modified, indicating the importance of sumoylation involved in the neurological diseases. In this review, we summarize the growing findings on protein sumoylation in neuronal function and dysfunction. It is essential to have a thorough understanding on the mechanism how sumoylation contributes to neurological diseases in developing efficient therapy for these diseases.

Sumoylation in Lens Differentiation and Pathogenesis.

Sumoylation, a post-translational modification discovered over a decade ago, turns out to be a very important regulatory mechanism mediating multiple cellular processes. Recent studies from our laboratory and others also revealed that it plays a crucial role in regulating both differentiation and pathogenesis of the ocular lens. This review will summarize these progresses.

Molecular Cloning and Developmental Expression Patterns of the Striatin Gene Encoding A Member of the Regulatory Subunits for the Protein Serine/Threonine Phosphatase-2A in Fish.

PURPOSE: The protein phosphatase-2A (PP-2A) is one of the most important serine/threonine phosphatases in eukaryotes. The holoenzyme of PP-2A consists of three subunits: a scaffold A subunit, a catalytic C subunit and a regulatory B subunit. While both A and C subunits are coded by two different genes, the B subunits exist in 26 or more isoforms which are encoded by at least 15 different genes. Previous studies have shown that besides regulating specific PP-2A activity, various B subunits may have other functions. To explore the possible roles of the regulatory subunits of PP-2A in vertebrate development, we have cloned the gene encoding goldfish striatin, a member of the B'" family regulatory subunits for PP-2A, and determined their tissue-specific and temporal expression patterns. METHODS: The cDNA cloning was conducted with RT-PCR-based RACE. The mRNA expression levels for the goldfish striatin were analyzed with RT-PCR. The expression levels of the striatin protein from goldfish were determined with Western blot analysis. The semi-quantitation of the mRNA and protein expression levels was conducted with the software of U-scanning. RESULTS: Our study revealed that the full length cDNA for striatin consists of 2965 bp coding for a deduced protein of 769 amino acids, which bears a very high level of amino acid sequence identity with the homolog protein from other species. The striatin mRNA is highly expressed in the kidney, to a less degree in brain, fin, muscle, liver, ovary and gill, and the lowest in testis and heart. Similar pattern of protein expression is detected in the above 9 tissues. During the development of goldfish, the striatin mRNA maintains a relatively high level at the 2-cell, multiple cell and blastula stages. Then, it drops down substantially at gastrula stage and fluctuates around this level in the next 8 different stages. At the protein level, the striatin maintained higher level from 2-cell to gastrula stages, then decreased at neurula and optic vesicle stages, and gradually increased again to peak at eye pigmentation stage, then slightly decreased in the next few stages of development. CONCLUSIONS: Our results suggest that the striatin may play an important role in regulating goldfish development and adult tissue homeostasis. While the former function may or may not occur through PP- 2A functions, the later function appears to occur via PP-2A activity.

Regulation of CREB Functions by Phosphorylation and Sumoylation in Nervous and Visual Systems.

CREB is an ubiquitous transcription factor regulating diverse cellular responses. Its phosphorylation at S133 is an essential event for its activation in both nervous and visual systems. The activated CREB is implicated in the regulation of development, protection, learning, memory and plasticity in the nerve system. Moreover, sumoylation, an important post-translational modification of protein, plays a key role in sustaining CREB activation in the rat hippocampus in order to enhance the long-term memory and other aspects. In the visual system, although the CREB activation by phosphorylation at S133 is similar to that as observed in the nervous system, the role of CREB sumoylation remains to be explored. This review will discuss the aspects of CREB functions and their regulation by phosphorylation and sumoylation in both systems.

The Male Abnormal Gene Family 21 (Mab21) Members Regulate Eye Development.

The male abnormal gene family contains 3 members, named mab21l1, mab21l2 and mab21l3. Since their first discovery in C. elegans, homologues of mab21l1 and mab21l2 have been found in Drosophila, Zebrafish, Xenopus, chicken, mouse and human. A number of studies have revealed that mab21 gene family members, mab21l1 and mab21l2, play important roles in regulating eye development. Here, we review the functions of the mab genes in regulating ocular development.

Melatonin protects hepatocytes against bile acid-induced mitochondrial oxidative stress via the AMPK-SIRT3-SOD2 pathway.

Mitochondrial oxidative damage is hypothesized to contribute to the pathogenesis of chronic cholestatic liver diseases. Melatonin, an indolamine synthesized in the pineal gland, shows a wide range of physiological functions, and is under clinical investigation for expanded applications. Melatonin has demonstrated efficient protective effects against various types of oxidative damage in the liver system. This study investigates the protective effects of melatonin pretreatment on glycochenodeoxycholic acid (GCDCA)-induced hepatotoxicity and elucidates the potential mechanism of melatonin-mediated protection. Melatonin markedly decreased mitochondrial ROS (mROS) production in L02 cells treated with 100 µM GCDCA, and inhibited GCDCA-stimulated cytotoxicity. Notably, melatonin exerted its hepatoprotective effects by upregulating sirtuin 3 (SIRT3) activity and its expression level, thus regulating superoxide dismutase 2 (SOD2) acetylation and inhibiting the production of mROS induced by GCDCA. Moreover, siRNA targeting SIRT3 blocked the melatonin-mediated elevation in mitochondrial function by inhibiting SIRT3/SOD2 signaling. Importantly, melatonin-activated SIRT3 activity was completely abolished by AMP-activated, alpha 1 catalytic subunit (AMPK) siRNA transfection. Similar results were obtained in rat with bile duct ligation or BDL. In summary, our findings indicate that melatonin is a novel hepatoprotective small molecule that functions by elevating SIRT3, stimulating SOD2 activity, and suppressing mitochondrial oxidative stress at least through AMPK, and that SIRT3 may be of therapeutic value in liver cell protection for GCDCA-induced hepatotoxicity.

Effect of nonmyeloablative unrelated fetal and neonatal murine peripheral blood mononuclear cell infusion on MRL/lpr mice.

For patients with refractory systemic lupus erythematosus (SLE), current medications are insufficient to control their condition, and new treatments are necessary. We investigated the effect of fetal and neonatal murine peripheral blood (FNPB) mononuclear cells on MRL/lpr lupus-prone mice. Female MRL/lpr mice were randomized to three groups (control, radiation and infusion groups). The infusion group had significantly better results for survival rate, body weight increase, reduction of spleen index, serum anti-ds-DNA antibody, antinuclear antibodies (ANA) and creatinine (Cr), 24 h urine protein and pathological renal tissue lesions than either the control or radiation group. Graft versus host disease (GVHD) was not observed in MRL/lpr mice in the infusion group. The infusion group also had better hematogenesis reconstruction than the radiation group. Flow cytometry analysis revealed a significant increase in Th1, CD8+ T and T reg cells and a reduction in Th2, CD4+ T and Th17 cells in the peripheral blood of the radiation and infusion groups compared with the control group. Immunocytochemical assay revealed a significant increase in serum transforming growth factor (TGF)-ß and a significant reduction in interleukin (IL)-17 in the radiation and infusion groups compared with the control group. Therefore, our study showed that FNPB mononuclear cell infusion has a significant role in regulating CD4+ T cells, Th1/Th2, Th17/T reg balance and their corresponding cytokines in MRL/lpr mice. The FNPB mononuclear cell infusion provided evidence in animals and suggested a potential clinical application for umbilical cord blood transplantation to treat SLE patients.

Site-specific proteolysis of cyclooxygenase-2: a putative step in inflammatory prostaglandin E(2) biosynthesis.

Cyclooxygenase-2 (COX-2) catalyzes the rate-limiting step in inflammatory prostanoid biosynthesis. Transcriptional, post-transcriptional, and post-translational covalent modifications have been defined as important levels of regulation for COX-2 gene expression. Here, we describe a novel regulatory mechanism in primary human cells involving regulated, sequence-specific proteolysis of COX-2 that correlates with its catalytic activity and ultimately, the biosynthesis of prostaglandin E(2) (PGE(2)). Proinflammatory cytokines induced COX-2 expression and its proteolysis into stable immunoreactive fragments of 66, 42-44, 34-36, and 28 kDa. Increased COX-2 activity (PGE(2) release) was observed coincident with the timing and degree of COX-2 proteolysis with correlation analysis confirming a linear relationship (R(2) = 0.941). Inhibition of induced COX-2 activity with non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 selective inhibitors also abrogated cleavage. To determine if NSAID inhibition of proteolysis was related to drug-binding-induced conformational changes in COX-2, we assayed COX-inactive NSAID derivatives that fail to bind COX-2. Interestingly, these compounds suppressed COX-2 activity and cleavage in a correlated manner, thus suggesting that the observed NSAID-induced inhibition of COX-2 cleavage occurred through COX-independent mechanisms, presumably through the inhibition of proteases involved in COX-2 processing. Corroborating this observation, COX-2 cleavage and activity were mutually suppressed by calpain/cathepsin protease inhibitors. Our data suggest that the nascent intracellular form of COX-2 may undergo limited proteolysis to attain full catalytic capacity.

Anti-solasodine glycoside single-chain Fv antibody stimulates biosynthesis of solasodine glycoside in plants.

We constructed a recombinant antibody fragment--single chain fragment-variable (scFv) antibody--derived from hybridoma cell lines to control the concentration of solasodine glycosides in hairy root cultures of Solanum khasianum transformed by the anti-solamargine (As)-scFv gene. The properties of the As-scFv protein expressed in Escherichia coli were almost identical to those of the parent monoclonal antibody (MAb). Up to 220 ng recombinant As-scFv was expressed per milligram of soluble protein in transgenic hairy root cultures of S. khasianum. The concentration of solasodine glycosides was 2.3-fold higher in the transgenic than in the wild-type hairy root, as reflected by the soluble As-scFv level and antigen binding activities. These results suggested that the scFv antibody expressed in transgenic hairy roots controlled the antigen level, thus representing a novel plant breeding methodology that can produce secondary metabolites.

Induction of differentiation by 1alpha-hydroxyvitamin D(5) in T47D human breast cancer cells and its interaction with vitamin D receptors.

The role of the active metabolite of vitamin D, 1,25 dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), in cell differentiation is well established. However, its use as a differentiating agent in a clinical setting is precluded due to its hypercalcaemic activity. Recently, we synthesised a relatively non-calcaemic analogue of vitamin D(5), 1alpha-hydroxyvitamin D(5) (1alpha(OH)D(5)), which inhibited the development of carcinogen-induced mammary lesions in culture and suppressed the incidence of chemically induced mammary carcinogmas in rats. In the present study, we determined the differentiating effects of 1alpha-(OH)D(5) in T47D human breast cancer cells and compared its effects with 1,25(OH)(2)D(3). Cells incubated with either 10 or 100 nM of the analogues inhibited cell proliferation in a dose-dependent manner, as measured by the dimethylthiazolyl-2,5-diphenyltetrazolium bromide (MTT) assay. Similar growth-inhibitory effects were also observed for MCF10(neo) cells. Both vitamin D analogues induced cell differentiation, as determined by induction of casein expression and lipid production. However, MCF10(neo) cells failed to respond to either vitamin D analogue and did not undergo cell differentiation. Since the cell differentiating effect of vitamin D is considered to be mediated via the vitamin D receptor (VDR), we examined the induction of VDR using reverse transcriptase-polymerase chain reaction (RT-PCR) in both cells. The results showed that, in T47D cells, both 1,25(OH)(2)D(3) and 1alpha(OH)D(5) induced VDR in a dose-dependent manner. Moreover, both analogues of vitamin D upregulated the expression of vitamin D response element-chloramphenicol acetyl transferase (VDRE-CAT). These results collectively indicate that 1alpha-(OH)D(5) may mediate its cell-differentiating action via VDR in a manner similar to that of 1,25(OH)(2)D(3).

Chemical modification of xylanase from Trichosporon cutaneum shows the presence of carboxyl groups and cysteine residues essential for enzyme activity.

The endo-beta-1,4-xylanase (EC 3.2.1.8) from Trichosporon cutaneum was chemically modified using amino acid-specific reagents. The enzyme does not bear arginines essential for activity, since 1,2-cyclohexanedione and 2,3-butanedione, although they modify the enzyme (after chromatographic analysis), have no effect on its activity. Reaction of the enzyme with tetranitromethane and N-acetylimidazole did not result in a significant activity loss as a result of modification of tyrosine residues. The water-soluble carbodiimide 1-[3-(dimethylamino) propyl]-3-ethylcarbodiimide inactivated the xylanase rapidly and completely in a pseudo-first-order process, and kinetic analysis indicated that at least one molecule of carbodiimide binds to the enzyme for inactivation. A mixture of neutral xylooligomers provided significant protection of the enzyme against this carbodiimide inactivation. Reaction of the xylanase with 2,4,6-trinitrobenzene sulfonic acid did not result in a significant activity loss as a result of modification of lysine residues. Titration of the enzyme with 5,5'-dithiobis-(2-nitrobenzoic acid) and treatment with iodoacetamide and p-chloromercuribenzoate indicated the presence of a free/active thiol group. Xylan completely protected the enzyme from inactivation by p-hydroxymercuribenzoate, suggesting the presence of cysteine at the substrate-binding site. Inactivation of xylanase by p-hydroxymercuribenzoate could be restored by cysteine.

Histopathologic changes seen in esophagectomy specimens from the high-risk region of Linxian, China: potential clues to an etiologic exposure?

Esophageal cancer is one of the most fatal cancers worldwide and is characterized by great variation in rates among different populations. Linxian, a county in Henan Province, located in north-central China, has one of the highest rates of esophageal squamous cell carcinoma in the world. Most squamous cell carcinomas in low-risk populations are attributable to alcohol and tobacco consumption, but the causative agents in high-risk populations are less clear. The prevention and treatment of esophageal cancer in high-risk regions, such as Linxian, are limited by our inability to identify these agent(s). During a preliminary histological review, the authors noticed characteristic findings in the arteries, nerves, and lymph nodes of esophagectomy specimens from Linxian and wondered whether these findings might offer clues to the cause of squamous cell carcinoma (eg, polycyclic aromatic hydrocarbon exposure) in the Linxian population. The purpose of this study was to report these previously undescribed histopathologic changes and to compare their presence and severity with those found in esophageal squamous cell carcinomas and adenocarcinomas from a lower-risk population in the United States. Forty esophagectomies were reviewed, including 13 squamous cell carcinomas from Linxian and 21 squamous cell carcinomas and six adenocarcinomas from the United States. The presence and severity of arteriosclerosis and myxoid degeneration of nerves and the presence of anthracosis in periesophageal lymph nodes were recorded. The prevalence and severity of these findings in the three groups of esophagectomies were compared. The esophageal squamous cell carcinomas from Linxian, China, had a higher prevalence of arteriosclerotic vessels, nerves with myxoid degeneration, and anthracotic lymph nodes than the squamous cell carcinomas from the United States (Wilcoxon test, P < .04 for all comparisons). There were also significant differences in the prevalence of arteriosclerotic vessels and anthracotic lymph nodes between the esophageal squamous cell carcinomas from Linxian and the adenocarcinomas from the United States. Arteriosclerosis and the myxoid degeneration were significantly more severe in the esophageal squamous cell carcinomas from Linxian than in the esophageal squamous cell carcinomas or adenocarcinomas from the United States (Mantel trend test, P < .006 for all comparisons). Arteriosclerotic vessels, nerves with myxoid degeneration, and anthracotic lymph nodes can be seen in association with esophageal squamous cell carcinomas from the high-risk region of Linxian, China. These changes appear to be more prevalent and severe than those seen in association with esophageal squamous cell carcinomas or adenocarcinomas from a low-risk population in the United States. These characteristic changes may be causatively significant and may represent histological evidence of high-level environmental exposure to polycyclic aromatic hydrocarbons.