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BACKGROUND AND AIMS: This study assessed the prognostic value of LCR in patients with cancer-associated malnutrition (CAM). Systemic inflammatory markers, particularly the lymphocyte-to-C-reactive protein ratio (LCR), are related to the survival of patients with CAM. The present retrospective analysis based on a prospective multicenter cohort study, which involved 1,437 hospitalized patients with CAM. METHODS: The area under the receiver operating characteristic curve (AUC) of ten inflammatory indicators-LCR, advanced lung cancer inflammation index, neutrophil-to-lymphocyte ratio, prognostic nutritional index, modified Glasgow prognostic score, systemic immune-inflammation index, albumin-to-globulin ratio, LCR score, glucose-to-lymphocyte ratio, and platelet-to-lymphocyte ratio-were constructed. Nutritional status, blood markers, and quality of life (QoL) were evaluated within 48 h of admission. The overall survival (OS) was evaluated from September 1 to December 29, 2021. RESULTS: A total of 1,431 cancer patients diagnosed with malnutrition based on the Global Leadership Initiative on Malnutrition (GLIM) criteria. Male patients were 62.8% of all, and the mean age was 60.66 years old. The AUC of LCR was higher than that of other inflammatory markers. The restricted cubic spline (RCS) of the Hazard ratios (HRs) showed an inverse L-shaped relationship with LCR. In addition, patients with low LCR had significantly poorer OS than those with high LCR. The addition of LCR to the model increased the predictive ability of 1-year mortality (AUC increase of 0.036), 3-year mortality (AUC increase of 0.038), and 5-year mortality (AUC increase of 0.031). CONCLUSIONS: Assessing the LCR can help the medical staff identify cancer patients with nutritional deficiency at high risk of oncological outcomes and develop individualized therapeutic strategies.
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Globulinas , Desnutrição , Neoplasias , Biomarcadores/metabolismo , Proteína C-Reativa/análise , Estudos de Coortes , Globulinas/metabolismo , Glucose/metabolismo , Humanos , Inflamação/complicações , Liderança , Linfócitos/química , Linfócitos/metabolismo , Masculino , Desnutrição/complicações , Neoplasias/complicações , Avaliação Nutricional , Estado Nutricional , Estudos Prospectivos , Qualidade de Vida , Estudos RetrospectivosRESUMO
A large field of view is normally desired for synchrotron x-ray imaging, while a small x-ray spot size is required for x-ray diffraction. A multiscale measurement system with an adjustable x-ray spot size is developed to accommodate different spot size requirements for in situ phase-contrast imaging and diffraction. The centers of a diffraction scintillator with a through-hole and an imaging scintillator are collinear with the x-ray beam. With the proof-of-principle experiments on a magnesium alloy under uniaxial tension, we demonstrate the feasibility of the multiscale measurement system for full azimuthal range diffraction measurements with improved resolution and large field of view strain field measurements via x-ray digital image correlation.
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Objective: To investigate the expression and clinical significance of exosomal miR-1231 in plasma of pancreatic cancer (PC) patients and pancreatic cancer cells. Methods: A total of 16 patients who were diagnosed with pancreatic cancer in Hunan Cancer Hospital were collected from April 2016 to August 2017. Meanwhile, 16 healthy volunteers were recruited as the healthy control group at the same period. The plasma exosomes were extracted, and the levels of miR-1231 were detected by qRT-PCR in PC and healthy control groups. Moreover, the clinicopathological significance of exosomal miR-1231 expression was analyzed. Furthermore, the expression of exosomal miR-1231 was detected in several pancreatic cancer cells (MIA PaCa-2, PANC-1, SW1990, AsPC-1 and BxPc-3) and two normal pancreatic epithelial cells (HPDE and human primary pancreatic epithelial cell). Results: qRT-PCR results showed that the expression level of miR-1231 in plasma exosomes of pancreatic cancer patients (1.06±0.46) was significantly lower than that in healthy controls (2.30±0.99; P<0.05). The levels of exosomal miR-1231 in patients with stage â -â ¡ (1.515±0.531), no distant metastasis (1.236±0.461) and no lymph node metastasis (1.337±0.522) were significantly higher than those with stage â ¢-â £ (0.848±0.224), distant metastasis (0.757±0.278) and lymph node metastasis (0.838±0.261), respectively (P<0.05 for all). In addition, there were no correlation between exosomal miR-1231 expression and age, sex, smoking history, CA19-9 levels and tumor sites (P>0.05). Furthermore, the expression level of exosomal miR-1231 in pancreatic cancer cell lines (0.142±0.135) was significantly lower than that in normal epithelial cells (1.127±0.179; P<0.05). Conclusions: The downregulation of exosomal miR-1231 in plasma of pancreatic cancer patients and pancreatic cancer cells suggests that it is related to the initiation and development of PC. It may be a new diagnostic and prognostic marker for PC.
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Exossomos/genética , MicroRNAs/metabolismo , Neoplasias Pancreáticas/metabolismo , Antígeno CA-19-9 , Estudos de Casos e Controles , Regulação para Baixo , Humanos , MicroRNAs/sangue , Pâncreas/metabolismo , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologiaRESUMO
The composition- and temperature-dependent liquid structures in eight Alrich-Cu binary alloys (from hypoeutectic Al93Cu7 to hypereutectic Al70Cu30) have been experimentally and computationally studied by x-ray diffraction (XRD) experiments and ab initio molecular dynamics (AIMD) simulations. The remarkable agreements of structure factors for all liquid Alrich-Cu alloys obtained from high-temperature high-energy XRD measurements and AIMD simulations have been achieved, which consolidates the analyses of structural evolutions in Alrich-Cu liquids during the cooling processing by AIMD simulations. The heat capacity of liquid Alrich-Cu alloys continuously increases and presents no abnormal peak when reducing the temperature, which differs from the reported prediction for 55-atom Alrich-Cu nanoliquids. The diffusivities of Al and Cu undergo an increasing deviation from Arrhenius behavior by tuning Cu concentration from 7 to 30 atomic percentages, correlated to the local ordering in these liquids by means of coordination number, bond-angle distribution, Honeycutt-Andersen index, bond-orientational order and Voronoi tessellation analyses. Upon cooling, the microstructure of the liquid Alrich-Cu alloys inclines to form Al2Cu crystal-like local atomic ordering, especially in the hypereutectic liquids. The favorable short-range ordering between Cu and Al atoms could cause the non-Arrhenius diffusion behavior.
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Layered Ti-Al metal composite (LMC) fabricated by hot-pressing and hot-rolling process displays higher ductility than that of both components. In this paper, a combination of digital image correlation (DIC) and X-ray tomography revealed that strain delocalization and constrained crack distribution are the origin of extraordinary tensile ductility. Strain delocalization was derived from the transfer of strain partitioning between Ti and Al layer, which relieved effectively the strain localization of LMC. Furthermore, the extensive cracks of LMC were restricted in the interface due to constraint effect. Layered architecture constrained the distribution of cracks and significantly relieved the strain localization. Meanwhile, the transfer of strain partitioning and constrained crack distribution were believed to inhibit the strain localization of Ti and change the deformation mechanisms of Ti. Our finding enriches current understanding about simultaneously improving the strength and ductility by structural design.
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X-ray diffraction and electrostatic levitation measurements, together with the ab initio molecular dynamics simulation of liquid Al(75)Cu(25) alloy have been performed from 800 to 1600 K. Experimental and ab initio molecular dynamics simulation results match well with each other. No abnormal changes were experimentally detected in the specific heat capacity over total hemispheric emissivity and density curves in the studied temperature range for a bulk liquid Al(75)Cu(25) alloy measured by the electrostatic levitation technique. The structure factors gained by the ab initio molecular dynamics simulation precisely coincide with the experimental data. The atomic structure analyzed by the Honeycutt-Andersen index and Voronoi tessellation methods shows that icosahedral-like atomic clusters prevail in the liquid Al(75)Cu(25) alloy and the atomic clusters evolve continuously. All results obtained here suggest that no liquid-liquid transition appears in the bulk liquid Al(75)Cu(25) alloy in the studied temperature range.
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UNLABELLED: This case-control study compared the associations of four widely used diet-quality scoring systems with the risk of hip fractures and assessed their utility in elderly Chinese. We found that individuals avoiding a low-quality diet have a lower risk of hip fractures in elderly Chinese. INTRODUCTION: Few studies examined the associations of diet-quality scores on bone health, and no studies were available in Asians and compared their validity and utility in a study. We assessed the associations and utility of four widely used diet-quality scoring systems with the risk of hip fractures. METHODS: A case-control study of 726 patients with hip fractures (diagnosed within 2 weeks) aged 55-80 years and 726 age- (within 3 years) and gender-matched controls was conducted in Guangdong, China (2009-2013). Dietary intake was assessed using a 79-item food frequency questionnaire with face-to-face interviews, and the Healthy Eating Index-2005 (HEI-2005, 12 items), the alternate Healthy Eating Index (aHEI, 8 items), the Diet Quality Index-International (DQI-I, 17 items), and the alternate Mediterranean Diet Score (aMed, 9 items) (the simplest one) were calculated. RESULTS: All greater values of the diet-quality scores were significantly associated with a similar decreased risk of hip fractures (all p trends <0.001). The multivariate-adjusted odds ratios (ORs) and 95% confidential intervals (95% CIs) comparing the extreme groups of diet-quality scores were 0.29 (0.18, 0.46) (HEI-2005), 0.20 (0.12, 0.33) (aHEI), 0.25 (0.16, 0.39) (DQI-I), and 0.28 (0.18, 0.43) (aMed) in total subjects; and the corresponding ORs ranged from 0.04 to 0.27 for men and from 0.26 to 0.44 for women (all p trends <0.05), respectively. CONCLUSIONS: Avoiding a low-quality diet is associated with a lower risk of hip fractures, and the aMed score is the best scoring system due to its equivalent performance and simplicity for the user.
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Dieta/normas , Fraturas do Quadril/etiologia , Fraturas por Osteoporose/etiologia , Idoso , Estudos de Casos e Controles , China/epidemiologia , Dieta/efeitos adversos , Dieta/estatística & dados numéricos , Inquéritos sobre Dietas , Dieta Mediterrânea/estatística & dados numéricos , Comportamento Alimentar , Feminino , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/prevenção & controle , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Medição de Risco/métodos , Fatores Sexuais , Fatores SocioeconômicosRESUMO
UNLABELLED: In this case-control study, we examined the relationship between the consumption of fruit and vegetables and risk of hip fractures in 646 pairs of incident cases and controls in elderly Chinese. We found that greater consumption of both fruit and vegetables in men and vegetables in women was associated with a lower risk of osteoporotic hip fractures in elderly Chinese. INTRODUCTION: The association between fruit and vegetable consumption and the risk of osteoporotic fractures remains controversial due to limited published evidence. The purpose of this study was to determine whether consuming fruits and vegetables has a protective effect against hip fractures. METHODS: Between January 2008 and December 2012, 646 (162 males, 484 females) incident cases (70.9 ± 6.8 years) of hip fractures were enrolled from five hospitals, with 646 sex- and age-matched (±3 years) controls (70.7 ± 6.8 years) from hospitals or the community. Face-to-face interviews were conducted to assess habitual dietary intakes using a 79-item food frequency questionnaire and various covariates by structured questionnaires. RESULTS: Multivariate conditional logistic regression analyses showed dose-dependent inverse correlations between the intake of total fruit (p-trend = 0.014), total vegetables (p-trend <0.001), fruits and vegetables combined (p-trend < 0.001) and the risk of hip fractures after adjustment for sociodemographic characteristics, dietary factors and other potential confounders. The adjusted odds ratios (95% confidence interval) for hip fractures in the top quartiles (vs. the lowest quartiles) for the intake of fruits, vegetables and the combination of fruits and vegetables were 0.53 (0.32-0.87), 0.37 (0.23-0.60) and 0.25 (0.15-0.41), respectively. Stratified analyses showed that the benefits remained significant in males (p = 0.001) but not in females (p = 0.210) (p-interaction 0.045). Among the subcategories of fruits and vegetables, similar associations were observed for all subgroups except light-coloured fruits. CONCLUSIONS: Our findings suggest that greater consumption of both fruits and vegetables in men and vegetables in women may decrease the risk of osteoporotic hip fractures in elderly Chinese.
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Comportamento Alimentar , Frutas , Fraturas do Quadril/prevenção & controle , Fraturas por Osteoporose/prevenção & controle , Verduras , Idoso , Estudos de Casos e Controles , China/epidemiologia , Dieta/estatística & dados numéricos , Inquéritos sobre Dietas , Feminino , Fraturas do Quadril/epidemiologia , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Atividade Motora , Fraturas por Osteoporose/epidemiologia , Medição de Risco/métodos , Fatores SocioeconômicosRESUMO
Phase retrieval extracts quantitative phase information from x-ray propagation-based phase-contrast images. Notwithstanding inherent approximations, phase retrieval using a single sample-to-detector distance (SDD) is very attractive, because it imposes no setup complications or additional radiation dose compared to absorption-based imaging. Considering the phase-attenuation duality (ε=δ/ß, where ε is constant), a simple absorption correction factor is proposed for the modified Bronnikov algorithm in x-ray propagation-based phase-contrast computed tomography (PPCT). Moreover, a practical method for calculating the optimal ε value is proposed, which requires no prior knowledge of the sample. Tests performed on simulation and experimental data successfully distinguished different materials in a quasihomogeneous and weakly absorbing sample from a single SDD-PPCT data point.
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UNLABELLED: Waxy corn starch was esterified with 2-octen-1-ylsuccinic anhydride (OSA) using response surface methodology. The molecular structure and paste properties were also investigated. Results indicated that the optimum parameters for esterification were as follows: reaction period 4 h, temperature 36.7 °C, pH of reaction system 8.3, concentration of starch slurry 36.9%, and amount of OSA 3%. The degree of substitution was 0.0187 and the reaction efficiency was 80.6%. The ester carbonyl group in OSA starch was characterized by Fourier Transform Infrared Spectroscopy at 1723 cm(-1). Compared with native starch, OSA derivative had higher peak viscosity, better freeze-thaw stability, and decreased gelatinization temperature and digestibility by porcine pancreatic alpha-amylase. Scanning electron microscopy showed that the gels from OSA starch had less and smaller pores; however, the native starch gels changed to sponge-like structure after 4 freezing/thawing cycles. The OSA modified waxy corn starch offered a potential to be used in frozen foods. PRACTICAL APPLICATION: (a) To optimize operating conditions to achieve OSA modified waxy corn starch with a high degree of substitution; (b) to give a deeper insight into the physicochemical properties of OSA modified waxy corn starch, which offered a potential to be used in frozen foods.
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Aditivos Alimentares/química , Amido/análogos & derivados , Anidridos Succínicos/química , Varredura Diferencial de Calorimetria , Fenômenos Químicos , Digestão , Esterificação , Aditivos Alimentares/síntese química , Aditivos Alimentares/metabolismo , Géis , Concentração de Íons de Hidrogênio , Hidrólise , Microscopia Eletrônica de Varredura , Estrutura Molecular , Concentração Osmolar , alfa-Amilases Pancreáticas/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Amido/química , Amido/metabolismo , Estatística como Assunto , Temperatura , Fatores de Tempo , Temperatura de Transição , ViscosidadeRESUMO
This study was designed to evaluate the usefulness of serum cystatin C (CysC) as a marker of renal function in 83 patients with diabetic nephropathy, considering multiple factors including tubular function and body mass index. Serum CysC was assayed using a particle-enhanced nephelometric immunoassay and the glomerular filtration rate (GFR) was obtained by measuring the plasma disappearance of the isotope (99m)Tc-diethylenetriamine penta-acetic acid. By comparing the correlation of CysC and serum creatinine (SCr) with GFR, it was concluded that CysC may be a better indicator of GFR than SCr in diabetic patients, in both the early hypertransfusion stage and in the late renal dysfunction stage. CysC showed a slightly higher sensitivity for renal function evaluation than SCr in patients with renal tubular dysfunction and moderate to severe proteinuria. In addition, CysC was not affected by the metabolic index. Thus, CysC may serve as an ideal endogenous marker of GFR in patients with diabetic nephropathy.
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Biomarcadores/sangue , Cistatina C/sangue , Diabetes Mellitus Tipo 2/sangue , Nefropatias Diabéticas/sangue , Taxa de Filtração Glomerular , Túbulos Renais/metabolismo , Área Sob a Curva , Creatinina/sangue , Diabetes Mellitus Tipo 2/patologia , Humanos , Testes de Função Renal , Túbulos Renais/patologia , Prognóstico , ProteinúriaRESUMO
A series of 41 papers by H. Zhong et al. are retracted.
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This study tested the hypothesis that milk has a direct effect on the establishment of infection with Teladorsagia circumcincta, and provides information on the effects of suckling on resilience to infection in young lambs. Of 46 six-week-old twin-born lambs, one from each twin was allowed to continue suckling (S-) and its twin-weaned (W-) while both were concurrently infected with an average of either 0 (-0; n=7/group), 250 (-250; n=8/group) or 1000 (-1000; n=8/group) third stage infective larvae (L3) of T. circumcincta per day, providing six treatment groups. All groups grazed minimally contaminated pasture, and after 42 days were slaughtered for necropsy. Low pasture larval contamination was confirmed in W0 and S0 lambs by faecal egg counts (FEC) of less than 30 eggs per gram (EPG) and burdens of less than 140 worms. There was no difference in FEC between weaned and suckled lambs. Within infection regime, total worm burdens were 55-60% greater in the weaned compared with their suckled counterparts (P=0.05), and represented 27 and 17%, respectively, net establishment of larvae. The greater worm burdens of both groups of weaned animals, which compared with their suckled counterparts, and of those infected with 1000 compared with 250 larvae per day, were associated with shorter female adults that had fewer eggs in utero, perhaps indicating intra-worm population regulation, but highlighting the limitation of FEC in assessing nematode burdens of such young lambs. There was no effect of infection on live weight gain of either weaned or suckled groups and the possibility was raised that, in such young lambs, immune unresponsiveness may be responsible. The major benefit of continued milk consumption appears to lie more in providing nutrients for enhanced growth rather than in improving resilience of the lambs to infection.
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Animais Lactentes/imunologia , Ostertagíase/veterinária , Contagem de Ovos de Parasitas/veterinária , Doenças dos Ovinos/parasitologia , Animais , Animais Recém-Nascidos , Fezes/parasitologia , Feminino , Masculino , Ostertagia/patogenicidade , Ostertagíase/imunologia , Ostertagíase/parasitologia , Distribuição Aleatória , Ovinos , Doenças dos Ovinos/imunologia , Desmame , Aumento de PesoRESUMO
A retrospective analysis of the long-term outcome of patients with membranous lupus nephropathy (MLN) was conducted. One hundred Chinese patients, 90 females and 10 males with a mean age of 32+/-9 years, with systemic lupus erythematosus and biopsy-proven MLN (ISN/RPS2003 classification criteria) were enrolled in this study. The patient and renal survivals were estimated by the Kaplan-Meier method and the risk factors associated with end-stage renal failure (ESRF) were assessed by the Cox proportional hazards regression analysis. The mean follow-up of all patients was 77.6+/-56 months. During follow-up, two patients died. Patient survival at 5 and 10 years was 98%. Renal survival at 5 and 10 years was 96.1% and 92.7%, respectively. Severe tubular-intersticial lesion (HR 66.514), nephrotic range proteinuria (HR 19.159) and refractoriness to treatments (HR 9.834) were independent risk factors for developing ESRF. Three of the six patients with ESRF had severe tubular-interstitial lesions on initial biopsy. Twenty-one patients underwent a repeat biopsy after 33months' (median time) follow-up, eight (38.1%) of these (class V superimposed class IV in 5, class V superimposed class III in 2 and class VI in 1) had transformed and three (37.5%) of them progressed to ESRF. Complications included infection (13%), thrombosis (3%), avascular necrosis (3%), diabetes mellitus (4%) and skin cancer (1%). The rate of patient and renal survival was high in this group of patients with MLN.
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Povo Asiático , Glomerulonefrite Membranosa/terapia , Falência Renal Crônica/terapia , Lúpus Eritematoso Sistêmico/complicações , Nefrite Lúpica/terapia , Adulto , Povo Asiático/estatística & dados numéricos , China/epidemiologia , Progressão da Doença , Feminino , Seguimentos , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/etnologia , Glomerulonefrite Membranosa/etiologia , Glomerulonefrite Membranosa/mortalidade , Glomerulonefrite Membranosa/patologia , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/etnologia , Falência Renal Crônica/etiologia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/patologia , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/mortalidade , Lúpus Eritematoso Sistêmico/patologia , Lúpus Eritematoso Sistêmico/terapia , Nefrite Lúpica/complicações , Nefrite Lúpica/etnologia , Nefrite Lúpica/etiologia , Nefrite Lúpica/mortalidade , Nefrite Lúpica/patologia , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
It is well established that dietary protein supply can influence the peri-parturient breakdown of immunity to nematode parasites but there is no information on the importance of exposure to nematode larvae during pregnancy for this response. We investigated this by exposing housed pregnant sheep, scanned as carrying two lambs, to a vaccinating infection with a trickle mixed infection of Teladorsagia circumcincta and Trichostrongylus colubriformis larvae (L3) or to no infection during weeks - 9 to - 4 relative to parturition. At the beginning of week - 3 all sheep were treated with anthelmintic to remove any vaccinating worm burden and from week - 2 to week +6 received a trickle challenge infection with the same nematodes. Within each vaccinating treatment there were two nutritional treatments (no. = 20 per subgroup) designed to provide 1.5 or 1.0 and 1.3 or 0.8 of metabolisable protein (MP) requirement during pregnancy and lactation, respectively. Five ewes were necropsied during weeks +1 and +3 to measure worm burdens and mucosal inflammatory cells and the remainder maintained until week +6. Serum levels of total, IgA and IgE antibodies against L3 antigen of each nematode were measured.Scanning errors and lamb losses resulted in some ewes carrying and/or rearing only one lamb. Numbers of lambs reared was therefore introduced as a treatment effect. Vaccinating infection delayed the peri-parturient rise in faecal egg count (FEC) by an average of 2 weeks but its effect on FEC during the first 6 weeks of lactation was smaller and less persistent than that of dietary MP supply and single- v. twin-suckling.Populations of both nematodes were lower in association with high MP supply, vaccination and single suckling. These changes were associated with increases in numbers of mucosal mast cells (MMC) as a result of both increased MP supply and vaccination. Evidence for a more rapid return of host ability to limit populations of the abdominal nematode T. circumcincta than of the intestinal nematode T. colubriformis was associated with fewer eosinophils and more globule leucocytes (GL) in abomasal than in intestinal tissue.None of the serum antibody isotypes was affected by dietary protein supply. Total and IgA antibodies were maintained by a current larval (vaccinating) intake. IgA titres, however, increased progressively during pregnancy, especially in twin-bearing ewes. IgE titres appeared to be sensitive primarily to the reproductive cycle itself, peaking around parturition.This work supports the conclusion that availability of MP supply influences the recruitment and activity of cells of the immune armoury of the gastro-intestinal tract to nematode parasites. The precise outcome may differ with site and/or nematode species.
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The restoration of the C-type cytoplasmic male sterility (Cms) has been a common agriculture practice in the production of hybrid seed for many years. In this study, a series of crosses between select sterile and restorer lines, as well as a backcross population of (Cms-C77 x 6233) x 6233, were used to investigate the restoration of C-type Cms. Our results demonstrated that there was an inhibitor of the Rf5 restorer gene. This inhibitor gene, Rf-I, maps to chromosome 7 and is tightly linked with SSR markers, umc2326 and umc2327, at a genetic distance 4.7 and 3.4 cM, respectively. After analyzing our data combined with previous studies, we propose that the restoration of C-type Cms has two dominant genes, Rf4 and Rf5. Rf4 has the ability to restore all genotypes of Cms-C lines; however, there exists an inhibitor for the other restorer gene, Rf5; thus, it can restore only those genotypes of Cms-C lines lacking the Rf-I inhibitor.