Randomized Trial of Standard Adjuvant Chemotherapy Regimens Versus Capecitabine in Older Women With Early Breast Cancer: 10-Year Update of the CALGB 49907 Trial.

PURPOSE: Older women with breast cancer remain under-represented in clinical trials. The Cancer and Leukemia Group B 49907 trial focused on women age 65 years and older. We previously reported the primary analysis after a median follow-up of 2.4 years. Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine. We now update results at a median follow-up of 11.4 years. PATIENTS AND METHODS: Patients age 65 years or older with early breast cancer were randomly assigned to either standard adjuvant chemotherapy (physician's choice of either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin) or capecitabine. An adaptive Bayesian design was used to determine sample size and test noninferiority of capecitabine. The primary end point was RFS. RESULTS: The design stopped accrual with 633 patients at its first sample size assessment. RFS remains significantly longer for patients treated with standard chemotherapy. At 10 years, in patients treated with standard chemotherapy versus capecitabine, the RFS rates were 56% and 50%, respectively (hazard ratio [HR], 0.80; P = .03); breast cancer-specific survival rates were 88% and 82%, respectively (HR, 0.62; P = .03); and overall survival rates were 62% and 56%, respectively (HR, 0.84; P = .16). With longer follow-up, standard chemotherapy remains superior to capecitabine among hormone receptor-negative patients (HR, 0.66; P = .02), but not among hormone receptor-positive patients (HR, 0.89; P = .43). Overall, 43.9% of patients have died (13.1% from breast cancer, 16.4% from causes other than breast cancer, and 14.1% from unknown causes). Second nonbreast cancers occurred in 14.1% of patients. CONCLUSION: With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor-negative disease. Competing risks in this older population dilute overall survival benefits.

[Screening results and influencing factors of upper gastrointestinal carcinoma and precancerous lesions in Feicheng City].

Objective: To clarify the situation of the detection of upper gastrointestinal cancer and precancerous lesions in the Feicheng city and discuss the possible influencing factors. Methods: A cluster sampling method was used to determine the participants. A unified questionnaire was used to investigate the basic information including history of alcohol intake, smoking and chinese tea, as well as other eating habits, medical history of digestive tract and cancer. Endoscopy was used to to screen the patients with upper gastrointestinal cancer and precancerous lesions. Influential factors were explored by non-conditional logistic regression model. Results: 911 of 7 291participants were positive, and the total detection rate was 12.49%. The total positive detection rate of male and female was 17.94% and 8.71%, respectively (P<0.001). Multivariate logistic regression analysis showed that the sex (OR=0.527, 95%CI: 0.440-0.631), age (OR=2.037, 95%CI: 1.849-2.245), smoking (OR=1.240, 95%CI: 1.014-1.516) and alcohol consumption (OR=1.232, 95%CI: 1.012-1.500) , meat and protein intake (OR=0.794, 95%CI: 0.638-0.987) and drink tea (OR=1.233, 95%CI: 1.056-1.440) may be influencing factors of the total detection rate of upper gastrointestinal cancer and precancerosis. Conclusions: In Feicheng city, intake of meat and protein is the protective factor of the upper gastrointestinal cancer and precancerous lesions. Men, aged, smoking, drinking and tea will increase the risk of upper gastrointestinal cancer and precancerous lesions.

Change in Pneumococcus Serotypes but not Mortality or Morbidity in Pre- and Post-13-Valent Polysaccharide Conjugate Vaccine Era: Epidemiology in a Pediatric Intensive Care Unit over 10 Years.

Aim: Pneumococcus is a common commensal and an important pathogen among children for which immunization is available. Some serotypes occasionally cause severe pneumococcal disease with high mortality and morbidity. We reviewed all pneumococcal serotypes and mortality/morbidity in a pediatric intensive care unit (PICU) following universal pneumococcal conjugate vaccine (PCV) immunization. Methods: A 13-valent PCV was introduced in the universal immunization program in late 2011 in Hong Kong. We retrospectively reviewed all pneumococcal serotypes in the pre-(2007-11) and post-(2012-16) 13-valent PCV era. Results: There were 29 (1.9%) PICU patients with pneumococcal isolation, of which 6 died (20% motality). Serogroups 6 and 19 predominated before and Serogroup 3 after 2012. In the post-13-valent PCV era, the prevalence of pneumococcus isolation in PICU was increased from 1 to 2% (p = 0.04); Serogroup 3 was the major serotype of morbidity, despite supposedly under vaccine coverage. The majority of pneumococcus were penicillin-sensitive (94%) in the post 13-valent PCV era. All pneumococcus specimens were sensitive to cefotaxime and vancomycin. Binary logistic regression showed that there were reductions in Serogroup 6 (odds ratio [OR], 0.050; 95% confidence interval [CI], 0.004-0.574; p = 0.016) and Serogroup 19 (odds ratio [OR], 0.105; 95% confidence interval [CI], 0.014-0.786; p = 0.028) but not mortality or morbidity for patients admitted after 2012. Conclusions: SPD is associated with significant morbidity and mortality, despite treatment with systemic antibiotics and ICU support. The expanded coverage of 13-valent PCV results in the reduction of Serotypes 6 and 19 but not mortality/morbidity associated with SPD in the setting of a PICU.

Biotransformation of ginsenoside Rb1 to ginsenoside Rg3 by endophytic bacterium Burkholderia sp. GE 17-7 isolated from Panax ginseng.

AIMS: To isolate a novel endophytic bacterium from Panax ginseng that could have excellent properties in converting ginsenoside Rb1 to ginsenoside Rg3. METHODS AND RESULTS: Based on a 16S rDNA gene sequence, the strain named GE 17-7 was identified as Burkholderia sp. This strain has shown the highest activity in converting ginsenoside Rb1 to 20(S)-ginsenoside Rg3. During the biotransformation of ginsenoside Rb1, the final metabolite was identified by nuclear magnetic resonance analysis and the transformation pathway of ginsenoside Rb1 was also identified by thin-layer chromatography and high performance liquid chromatography analysis in this study. CONCLUSIONS: We have successfully isolated a ß-glucosidase-producing endophytic bacterium GE 17-7 from P. ginseng. Ginsenoside Rg3 was produced by strain GE 17-7 from ginsenoside Rb1 via ginsenoside Rd. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of the conversion of major ginsenoside Rb1 into minor ginsenoside Rg3 by fermentation with Burkholderia sp. endophytic bacteria in P. ginseng. These results suggest a new preparation method for ginsenoside Rg3 using strain GE 17-7 in the pharmaceutical industry.

Changes of microRNA-1, -15b and -21 levels in irradiated rat hearts after treatment with potentially radioprotective drugs.

The aim of this study was to measure expression levels of microRNAs (miRNAs) (miRNA-1, -15b and -21) in the rat myocardium after a single dose of ionizing radiation (6-7 Gy/min, total 25 Gy). The rats were treated with selected drugs (Atorvastatin, acetylsalicylic acid (ASA), Tadalafil, Enbrel) for six weeks after irradiation. MiRNAs levels were measured by RT-qPCR. Irradiation down-regulated miRNA-1 in irradiated hearts. In Tadalafil- and Atorvastatin-treated groups, miRNA-1 expression levels were further decreased compared with irradiated controls. However, Enbrel increased miRNA-1 level in irradiated hearts similarly to that in non-irradiated untreated group. Increase of miRNA-15b is pro-apoptotic in relationship with ischemia. Irradiation caused down-regulation of miRNA-15b. Administration of ASA in the irradiated group resulted in the increase of miRNA-15b expression compared to non-treated controls without irradiation. After Enbrel administration, miRNA-15b levels were overexpressed compared to non-treated normal group. MiRNA-21 belongs to the most markedly up-regulated miRNAs in response to cardiogenic stress. MiRNA-21 was increased nearly 2-fold compared to non-treated hearts whereas Tadalafil reduced miRNA-21 levels (about 40 %). Our study suggests that Enbrel and Tadalafil changed miRNAs expression values of the irradiated rats to the values of non-irradiated controls, thus they might be helpful in mitigation of radiation-induced toxicity.

Biotransformation of ginsenoside Rb1 to ginsenoside C-K by endophytic fungus Arthrinium sp. GE 17-18 isolated from Panax ginseng.

UNLABELLED: This research aimed to isolate ß-glycosidase-producing endophytic fungus in Panax ginseng to achieve biotransformation of ginsenoside Rb1 to ginsenoside C-K. Of these 15 ß-glucosidase-producing endophytic fungus isolated from ginseng roots, a ß-glucosidase-producing endophytic fungi GE 17-18 could hydrolyse major ginsenosides Rb1 to minor ginsenoside C-K with metabolic pathways: ginsenoside Rb1→ginsenoside Rd→ginsenoside F2→ginsenoside C-K. Phylogenetic analysis of ITS gene sequences indicated that the strain GE 17-18 belongs to the genus Arthrinium and is most closely related to Arthrinium sp. HQ832803.1. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to provide information of cultivable ß-glycosidase-producing Endophytic fungus in Panax ginseng. The strain GE 17-18 has potential to be applied on the preparation for minor ginsenoside C-K in pharmaceutical industry.

Effect of Bacillus subtilis CGMCC 1.1086 on the growth performance and intestinal microbiota of broilers.

AIMS: Probiotics have been proved to be the most preferred and effective alternative to antibiotics as growth promoter and pathogens inhibitor in poultry industry. In this study Bacillus subtilis CGMCC 1.1086 as a probiotic bacterium was administered in diet and its effects on both the growth performance and the caecal microbiota of broilers were evaluated. METHODS AND RESULTS: A total of 240 male Arbor Acres (AA) broilers were randomly allocated into two treatment groups of basal diet without any addition of probiotics and basal diet containing B. subtilis CGMCC 1.1086. The body weight of broilers was measured individually at 32, 39 and 46 days of bird age. Furthermore, MiSeq high-throughput sequencing analysis of 16S rRNA was used to investigate the bacterial community structure in the caeca of broilers. The results indicated that broilers receiving diet supplemented with B. subtilis CGMCC 1.1086 showed 27·7% higher daily weight gain than those of control during 2 weeks. The feed conversion ratio (FCR) of B. subtilis CGMCC 1.1086 group was also improved by 10·3%. In the caeca of broilers fed with B. subtilis CGMCC 1.1086, the relative abundance of Alistipes, Odoribacter, Ruminococcus, Blautia and Desulfovibrio were higher, while the potential pathogens such as Staphylococcus and Escherichia-Shigella were lower than those of control. CONCLUSIONS: The probiotic B. subtilis CGMCC 1.1086 can effectively improve the growth performance and FCR of broilers via the beneficial modulation of caecal microbiota. SIGNIFICANCE AND IMPACT OF THE STUDY: The effect of B. subtilis on growth performance of broilers was evaluated and the relationship between growth and caecal microbiota was revealed. The results of this study help to promote application of probiotics in poultry industry.

Novel genetic male sterility developed in (Capsicum annuum x C. chinense) x C. pubescens and induced by HNO2 showing Mendelian inheritance and aborted at telophase of microspore mother cell stage.

A novel genetic male sterile germplasm was developed by successively crossing of (C. annuum x C. chinense) x C. pubescens and by chemical mutagenesis in pepper. The sterile anthers showed morphological abnormalities, but pistils developed normally with fine pollination capability. We investigated fertility segregation through sib-crossing of the same strains and test crossing by male sterile plants with 6 advanced inbred lines. The results showed that male fertility in the pepper was dominant in the F1 generation and segregated at a rate of 3:1 in the F2 generation, suggesting that monogenic male sterility was recessive and conformed to Mendelian inheritance. Cyto-anatomy analysis revealed that microspore abortion of sterile anthers occurred during telophase in the microspore mother cell stage when tapetal cells showed excessive vacuolation, resulting in occupation of the loculi. The microspore mother cells self-destructed and autolyzed with the tapetum so that meiosis in pollen mother cells could not proceed past the tetrad stage.

Growth performance and meat quality of broiler chickens supplemented with Rhodopseudomonas palustris in drinking water.

1. The effect of the bacterium, Rhodopseudomonas palustris, on the growth performance and meat quality of broiler chickens was investigated. 2. A total of 900-d-old Arbor Acres broilers were allocated to three experimental treatments for 6 weeks. Chicks were administered with R. palustris in drinking water as follows: (i) control group without R. palustris; (ii) treatment 1 (R1) with R. palustris of 8 × 10(9) cells per chick per day in drinking water; (iii) treatment 2 (R2) with R. palustris of 1.6 × 10(10) cells per chick per day in drinking water. 3. The results showed that, compared with that of control, both groups of R. palustris treatment increased daily weight gain and improved feed conversion ratio of broiler chickens significantly during the whole growing period of 6 weeks. 4. Both total and glutamic acid contents of chicken breast fillet in R. palustris treatment R2 were higher, while the fat content was lower, than those of the control group. Furthermore, R. palustris treatments also improved sensory attributes of chicken breast fillet. 5. As a probiotic providing rich nutrients and biological active substances, R. palustris administration in drinking water displayed a growth promoting effect and improved meat quality of broiler chickens.

Diversity of cultivable ß-glycosidase-producing micro-organisms isolated from the soil of a ginseng field and their ginsenosides-hydrolysing activity.

UNLABELLED: This research aimed to explore the diversity of cultivable ß-glycosidase-producing micro-organisms in ginseng field soil. Fifty-three strains showing ß-glucosidase activity were isolated from a ginseng field, using a newly designed Esculin-R2A agar. All the isolated strains belonged to the genus Agrobacterium, Arthrobacter, Burkholderia, Dyella, Edaphobacter, Luteibacter, Mucilaginibacter, Paenibacillus, Phenylobacterium, Pseudomonas, Sphingomonas and Streptomyces. The main ß-glucosidase-producing micro-organisms in the ginseng field soil were Sphingomonas, Burkholderia, Luteibacter and Streptomyces, while concentrations of Agrobacterium, Arthrobacter, Paenibacillus and Pseudomonas were relatively low. Of these micro-organisms, the strain GS 09 could hydrolyse major ginsenosides Rb1, Rb2 and Rc to the active metabolite compound K. The strain GS 09 belonged to the genus Sphingomonas, and its 16S rRNA gene sequence showed 100% similarities with that of Sphingomonas asaccharolytica. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study to provide information of cultivable ß-glycosidase-producing micro-organisms in ginseng field soil. The strain GS 09 has potential to be applied on the preparation for minor ginsenoside C-K in pharmaceutical industry.

Craniocervical arterial dissections as sequelae of chiropractic manipulation: patterns of injury and management.

OBJECT: Chiropractic manipulation of the cervical spine is a known cause of craniocervical arterial dissections. In this paper, the authors describe the patterns of arterial injury after chiropractic manipulation and their management in the modern endovascular era. METHODS: A prospectively maintained endovascular database was reviewed to identify patients presenting with craniocervical arterial dissections after chiropractic manipulation. Factors assessed included time to symptomatic presentation, location of the injured arterial segment, neurological symptoms, endovascular treatment, surgical treatment, clinical outcome, and radiographic follow-up. RESULTS: Thirteen patients (8 women and 5 men, mean age 44 years, range 30-73 years) presented with neurological deficits, head and neck pain, or both, typically within hours or days of chiropractic manipulation. Arterial dissections were identified along the entire course of the vertebral artery, including the origin through the V(4) segment. Three patients had vertebral artery dissections that continued rostrally to involve the basilar artery. Two patients had dissections of the internal carotid artery (ICA): 1 involved the cervical ICA and 1 involved the petrocavernous ICA. Stenting was performed in 5 cases, and thrombolysis of the basilar artery was performed in 1 case. Three patients underwent emergency cerebellar decompression because of impending herniation. Six patients were treated with medication alone, including either anticoagulation or antiplatelet therapy. Clinical follow-up was obtained in all patients (mean 19 months). Three patients had permanent neurological deficits, and 1 died of a massive cerebellar stroke. The remaining 9 patients recovered completely. Of the 12 patients who survived, radiographic follow-up was obtained in all but 1 of the most recently treated patients (mean 12 months). All stents were widely patent at follow-up. CONCLUSIONS: Chiropractic manipulation of the cervical spine can produce dissections involving the cervical and cranial segments of the vertebral and carotid arteries. These injuries can be severe, requiring endovascular stenting and cranial surgery. In this patient series, a significant percentage (31%, 4/13) of patients were left permanently disabled or died as a result of their arterial injuries.

Role of oxidative tissue injury in the pathophysiology of experimentally induced equine laminitis: a comparison of 2 models.

BACKGROUND: Oxidative stress reportedly plays a role in sepsis-induced organ dysfunction and failure in many species. In septic horses, laminae are targeted; evidence of laminar oxidative stress has been reported experimentally in the black walnut extract (BWE) model. Carbohydrate (CHO)-induced laminitis may be more similar to clinical sepsis-related laminitis than the BWE model in that animals with CHO-induced disease commonly develop laminar failure. The role of oxidative stress in the CHO model remains unknown. HYPOTHESIS/OBJECTIVES: Markers of oxidative stress will be increased in laminae from horses with BWE- and CHO-induced laminitis. ANIMALS: Banked laminar tissue from various time points from animals subjected to BWE (n = 15) and CHO (n = 20) protocols. METHODS: Laminar 4-hydroxynonenal (4-HNE) and protein carbonyl content were evaluated by slot blot analysis. Laminar 3-nitrotyrosine (3-NT) immunohistochemistry was performed. RESULTS: The number of laminar 3-NT (+) cells was increased at developmental and Obel grade 1 (OG1) time points in the BWE model (versus control [CON]; P= .013) and lower in OG1 tissues than CON in the CHO model (P = .04). No change in 4-HNE content was observed in the CHO model, and no increase in laminar protein carbonyl content was present in either model (P > .05). CONCLUSIONS AND CLINICAL IMPORTANCE: These results do not support a prominent role for oxidative stress at examined time points in CHO-overload laminitis and support transient oxidative stress in the BWE model. Tissue oxidation does not appear to be a central early pathophysiologic event in CHO-associated laminitis.

Immunohistochemical profile and fluorescence in situ hybridization analysis of diffuse large B-cell lymphoma in northern China.

CONTEXT: Gene expression profiling of diffuse large B-cell lymphoma using complementary DNA microarrays has revealed 2 major prognostic groups in Western countries: germinal center B-cell-like and nongerminal center B-cell-like lymphomas. Immunohistochemical analysis using antibodies specific for CD10, BCL6, and MUM1 has been proposed as a surrogate for gene expression profiling. OBJECTIVE: To study the immunohistochemical features of diffuse large B-cell lymphoma cases from northern China because geographic differences for this disease are known to exist. DESIGN: Morphologic, immunohistochemical, and fluorescence in situ hybridization analyses of 63 cases of diffuse large B-cell lymphoma from northern China. RESULTS: There were 38 men and 25 women with a median age of 57 years (range, 12-87 years). CD10 was positive in 19 cases (30%), BCL6 was positive in 22 cases (35%), and MUM1 was positive in 32 cases (51%). Twenty-one (33%) cases were germinal center B-cell-like lymphoma, and 42 (67%) were nongerminal center B-cell-like lymphoma. BCL2 was expressed more often in nongerminal center B-cell-like disease versus germinal center B-cell-like disease (60% versus 24%, P = .01) and in nodal versus extranodal (64% versus 30%, P = .01) cases. Fluorescence in situ hybridization analysis showed BCL6, MYC , and BCL2 rearrangements in 11 of 32 (34%), 8 of 27 (30%), and 11 of 50 (22%) cases, respectively. CONCLUSIONS: These results add to what is known about the geographic variation of diffuse large B-cell lymphomas. In northern China, the frequency of the germinal center B-cell-like type and BCL6 expression and/or BCL6 rearrangement is less and the frequency of MYC rearrangement is greater than have been reported in Western countries.

Antioxidant efficacy of curcuminoids from turmeric ( Curcuma longa L.) powder in broiler chickens fed diets containing aflatoxin B1.

A 3-week-feeding study (1-21 d post-hatch) was conducted to evaluate the efficacy of total curcuminoids (TCMN), as an antioxidant, to ameliorate the adverse effects of aflatoxin B1 (AFB1) in broiler chickens. Turmeric powder (Curcuma longa L.) that contained 2.55 % TCMN was used as a source of TCMN. Six cage replicates of five chicks each were assigned to each of six dietary treatments, which included: basal diet; basal diet supplemented with 444 mg/kg TCMN; basal diet supplemented with 1.0 mg/kg AFB1; basal diet supplemented with 74 mg/kg TCMN and 1.0 mg/kg AFB1; basal diet supplemented with 222 mg/kg TCMN and 1.0 mg/kg AFB1; basal diet supplemented with 444 mg/kg TCMN and 1.0 mg/kg AFB1. The addition of 74 and 222 mg/kg TCMN to the AFB1 diet significantly (P < 0.05) improved weight gain and feed efficiency. Increase (P < 0.05) in relative liver weight in birds fed AFB1 was significantly reduced (P < 0.05) with the addition of 74, 222 and 444 mg/kg TCMN to the AFB1 diet. The inclusion of 222 mg/kg TCMN ameliorated the adverse effects of AFB1 on serum chemistry in terms of total protein, albumin and gamma-glutamyl transferase activity. The decreased antioxidant functions due to AFB1 were also alleviated by the inclusion of 222 mg/kg TCMN. It is concluded that the addition of 222 mg/kg TCMN to the 1.0 mg/kg AFB1 diet demonstrated maximum antioxidant activity against AFB1.

Tissue concentrations of 4-HNE in the black walnut extract model of laminitis: indication of oxidant stress in affected laminae.

In the septic horse prone to laminitis, a similar activation of the innate immune system appears to occur as reported in the septic human prone to organ failure. Because oxidant injury plays a central role in organ failure occurring due to an overzealous innate immune response in human sepsis, this study was performed to determine whether there was evidence of oxidant stress in the laminar tissue in the early stages of laminitis. 4-Hydroxy-2-nonenal (4-HNE), a lipid aldehyde that forms due to lipid peroxidation occurring during episodes of oxidant stress, readily forms adducts with cellular proteins; these adducts can be assessed as a marker of oxidant stress in the form of lipid peroxidation. In this study, a slot blot technique was used to assess 4-HNE adduct concentrations in the laminae, lung, liver, and intestinal tract in the black walnut extract (BWE) model of laminitis. Significant increases in laminar 4-HNE adduct concentrations were identified at two early stages in the BWE model, in the absence of such changes in the other tissues. These data indicate that oxidant stress may play an important role in the laminar failure in laminitis, and further support the concept that a poor antioxidant response in the laminae relative to other equine tissues may be responsible for failure of the laminae in the septic horse. In contrast, tissues such as the lung and liver that undergo oxidant injury in human sepsis appear to be relatively protected in horses.

Effects of several Chinese herbal aqueous extracts on human sperm motility in vitro.

The effects of six kinds of aqueous extracts of Chinese herbal medicine (Astragalus membranaceus, Acanthopanacis senticosi, Panax genseng and Ophiopogon japonicus, P. genseng and Aconitum carmichaeli, Salviae miltiorrhiae, Polyporus umbellatus polysaccharide) on sperm motility characteristics of 30 infertile male volunteers were studied in vitro with a computer-assisted sperm analysis at 15, 60 and 180 min after incubated with the drugs. The results showed that per cent viability, number of progressive motile spermatozoa, curvilinear velocity, average path velocity and amplitude of lateral head displacement were significantly enhanced by A. membranaceus (P < 0.05 or < 0.01), per cent viability, average path velocity and amplitude of lateral head displacement were significantly enhanced by A. senticosi (P < 0.05), but all the above were not affected by P. genseng and O. japonicus, P. genseng and A. carmichaeli, S. miltiorrhiae and P. umbellatus polysaccharide. It is suggested that A. membranaceus and A. senticosi can enhance the motility of human spermatozoa in vitro.

Non-point pollution from China's rural areas and its countermeasures.

Most lakes in the eastern part of China are eutrophic and non-point pollution accounts for more than half of the nutrient load to the lakes and reservoirs. Some efforts have been made to reduce the non-point source pollution in the catchments of sensitive water bodies. Technologies for the control of non-point pollution in Chinese rural areas are multipond systems, biogas fermentation, hilly area ecological agriculture, constructed wetlands, ecotone engineering and others. They are effective in the removal of nutrients from the runoff water or reduction of waste, and they are used with multi-purposes. To control non-point pollution, the cooperation with farmers and other residents in the countryside is the key to success, and the program has to consider their benefits. There are still many difficulties with its control, and more efforts are needed to develop suitable technologies and environmental education.

Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain.

Converging lines of evidence implicate the beta-amyloid peptide (Ass) as causative in Alzheimer's disease. We describe a novel class of compounds that reduce A beta production by functionally inhibiting gamma-secretase, the activity responsible for the carboxy-terminal cleavage required for A beta production. These molecules are active in both 293 HEK cells and neuronal cultures, and exert their effect upon A beta production without affecting protein secretion, most notably in the secreted forms of the amyloid precursor protein (APP). Oral administration of one of these compounds, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester, to mice transgenic for human APP(V717F) reduces brain levels of Ass in a dose-dependent manner within 3 h. These studies represent the first demonstration of a reduction of brain A beta in vivo. Development of such novel functional gamma-secretase inhibitors will enable a clinical examination of the A beta hypothesis that Ass peptide drives the neuropathology observed in Alzheimer's disease.

Multipond system: a sustainable way to control diffuse phosphorus pollution.

Diffuse pollution from agricultural land is one of the main causes for lake eutrophication. Multipond systems, an ancient invention in China, are composed of many tiny ponds and ditches, scattered in agricultural fields. After a long period of research in an experimental watershed in Liuchahe, it was found that multipond systems constitute diffuse pollution control. They have a large capacity for water storage and serve to control the export of water, suspended matter, and phosphorus. Multipond systems significantly reduce runoff velocity. Sediments and phosphorus retained in the Liuchahe watershed were 14.38 x 10(6) and 7016 kg yr-1, respectively (area 691.6 ha). Irrigation provides an effective way to recycle and remove phosphorus. The use of multipond systems is a sustainable way to recycle valuable nutrients and reduce their discharge and thus pollution of downstream lakes.