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The animal intestine is a complex ecosystem composed of host cells, gut microbiota and available nutrients. Gut microbiota can prevent the occurrence of intestinal diseases in animals by regulating the homeostasis of the intestinal environment. The intestinal microbiota is a complex and stable microbial community, and the homeostasis of the intestinal environment is closely related to the invasion of intestinal pathogens, which plays an important role in protecting the host from pathogen infections. Probiotics are strains of microorganisms that are beneficial to health, and their potential has recently led to a significant increase in studies on the regulation of intestinal flora. Various potential mechanisms of action have been proposed on probiotics, especially mediating the regulation mechanism of the intestinal flora on the host, mainly including competitive inhibition of pathogens, stimulation of the host's adaptive immune system and regulation of the intestinal flora. The advent of high‐throughput sequencing technology has given us a clearer understanding and has facilitated the development of research methods to investigate the intestinal microecological flora. This review will focus on the regulation of probiotics on the microbial flora of intestinal infections in livestock and poultry and will depict future research directions. [ABSTRACT FROM AUTHOR]

Vibrio harveyi is a common aquaculture pathogen causing diseases in a variety of aquatic animals. toxR, a conserved virulence‐associated gene in vibrios, is identified in V. harveyi 345, a pathogenic strain isolated from diseased fish. In this study, to gain insight into function of ToxR in V. harveyi, an in‐frame deletion of the toxR gene was constructed to reveal the role of ToxR in the physiology and virulence of V. harveyi. The statistical analysis showed no significant differences in the growth ability, motility, extracellular protease secretion, antibiotic susceptibility, virulence by intraperitoneal injection and the ability of V. harveyi to colonize the spleen and liver tissues of the pearl gentian grouper between the wild‐type (WT) and the toxR mutant. However, the deletion of toxR increased the biofilm formation. The structure of the V. harveyi biofilm was further analysed by using scanning electron microscopy (SEM) and confocal laser scanning microscopy, and the results showed that deletion of toxR increased the number and density of V. harveyi biofilm. Since biofilm production is flagella, exopolysaccharide (EPS) and lipopolysaccharide dependent, 16 of V. harveyi biofilm‐related genes were selected for further analysis. Based on quantitative real‐time reverse transcription‐PCR, the expression levels of these genes, including genes flrB, motY and mshA, flaE, flrA and gmhD, were significantly up‐regulated in the ΔtoxR+ strain as compared with the WT+ and C‐ΔtoxR strains during the early and mid‐exponential, while epsG, flaA, flaE, flgD, flgE, flrB, flrC, lpxB, motY, mshA and scrG genes were inhibited because of deletion of the toxR gene in the stationary growth phase. Our results indicate that ToxR plays an important role in controlling the biofilm in V. harveyi. [ABSTRACT FROM AUTHOR]

There is a causal relationship between dietary salt intake and blood pressure. A reduction in salt intake from the current world average of ∼10 g/day to the WHO recommended level of <5 g/day, lowers blood pressure and reduces the risk of cardiovascular disease and all-cause mortality. However, a few cohort studies have claimed that there is a J-shaped relationship between salt intake and cardiovascular risk, i.e. both high and low salt intakes are associated with an increased risk. These cohort studies have several methodological problems, including reverse causality, and inaccurate and biased estimation of salt intake, e.g. from a single spot urine sample with formulas. Recent studies have shown that the formulas used to estimate salt intake from spot urine cause a spurious J-curve. Research with inappropriate methodology should not be used to refute the robust evidence on the enormous benefits of population-wide reduction in salt intake. Several countries, e.g. Finland, the UK, have successfully reduced salt intake, which has resulted in falls in population blood pressure and deaths from stroke and ischaemic heart disease. Every country should develop and implement a coherent, workable strategy to reduce salt intake. Even a modest reduction in salt intake across the whole population will lead to a major improvement in public health, along with huge cost-savings to the healthcare service. [ABSTRACT FROM AUTHOR]

Aims: With a goal to identify specific essential oils that can control postharvest Rhizopus rot on strawberry and peach fruits, we performed screening for 26 essential oils based on their antifungal activity against Rhizopus stolonifer in vitro and investigated the underlying mechanism. Methods and Results: Mentha spicata (Ms), Mentha piperita (Mp), Thymus vulgaris CT carvacrol (Tc) and Thymus vulgaris CT thymol (Tt) exhibited strong inhibition on R. stolonifer growth in the screening. These essential oils increased plasma membrane permeability of R. stolonifer and resulted in the outflow of intercellular electrolyte, nucleic acid, protein and soluble sugar. Morphology of R. stolonifer mycelia was greatly altered by these essential oils. Hyphae treated by these essential oils exhibited high accumulation of superoxide anion and malonaldehyde. Combination of these essential oils in commercial package reduced Rhizopus rot on strawberry and peach fruits, with Mp showing the strongest efficiency. Conclusion: Ms, Mp, Tc and Tt essential oils inhibited R. stolonifer growth by targeting its plasma membrane and reduced Rhizopus rot on strawberry and peach fruits. Significance and Impact of the Study: This study provides potential applications of natural plant extract, as alternatives to tradition fungicides, to control postharvest decay on fruits and vegetables. [ABSTRACT FROM AUTHOR]

Summary: Pattern recognition receptors, such as Toll‐like receptors (TLRs), play an important role in the host defense against invading microbial pathogens. Their activation must be precisely regulated, as inappropriate activation or overactivation of TLR signaling pathways may result in inflammatory disorders, such as septic shock or autoimmune diseases. TMEM106A is a type II transmembrane protein constitutively expressed in macrophages. Our current study demonstrated that TMEM106A levels were increased in macrophages upon lipopolysaccharide (LPS) stimulation, as well as in the peripheral monocytes of patients with sepsis. Tmem106a knockout mice were more sensitive to lipopolysaccharide (LPS)‐induced septic shock than wild‐type mice. Further experiments indicated that Tmem106a ablation enhanced the expression of CD80, CD86 and major histocompatibility complex (MHC)‐II in mouse macrophages upon LPS stimulation, accompanied with up‐regulation of tumor necrosis factor (TNF)‐α, interleukin (IL)‐6, interferon (IFN)‐β and inducible nitric oxide synthase (iNOS), indicating the activation of macrophages and polarization towards the M1 inflammatory phenotype. Moreover, elevated mitogen‐activated protein kinase (MAPK) and nuclear factor kappa B (NF‐κB) signaling were found to be involved in the LPS‐induced inflammatory response in Tmem106a−/− macrophages. However, this effect was largely abrogated by macrophage deletion in Tmem106a−/− mice. Therefore, deficiency of Tmem106a in macrophages may enhance the M1 polarization in mice, resulting in inflammation. This suggests that TMEM106A plays an important regulatory role in maintaining macrophage homeostasis. [ABSTRACT FROM AUTHOR]

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Aims: To extract and identify the metabolites of strain A217 as well as its antifungal spectrum and control effect on various plant pathogens. Methods and Results: Strain A217 was identified as a Streptomyces sp. which was most similar to Streptomyces lienomycini. An antimicrobial spectrum test indicated that strain A217 inhibited several plant pathogenic fungi and strong antibacterial effect such as Phytophthora capsici, Botrytis cinerea, Sclerotinia sclerotiorum, Fusarium oxysporum, Pseudomonas syringae and Xanthomonas campestris. An in vivo tissue test demonstrated that the fermentation broth of strain A217 exerted therapeutic and protective effects of 49·47 and 61·60% respectively, on S. sclerotiorum. Additionally, the fermentation broth of A217 exerted control effects on walnut black spot disease in walnut leaves and branches amounting to 79·33 and 81·52% respectively. In a pot experiment, the fermentation broth exhibited a stronger protective and control effect (68·29%), as well as better bacteriostatic and disease control effects on Phytophthora blight of pepper, compared with Metalaxyl. Compounds possessing antifungal and antibacterial activities were obtained from the fermentation broth of strain A217, using column chromatography and HPLC. Chemical and structural analyses conducted using MS and nuclear magnetic resonance confirmed that these compounds were 1H‐pyrrole‐2‐carboxylic acid and 1H‐pyrrole‐2‐carboxamide. The EC50 values of compound 1H‐pyrrole‐2‐carboxylic acid1 for S. sclerotiorum and P. capsici were 20·13 and 50·36 μg ml−1 respectively. Compound 1H‐pyrrole‐2‐carboxamide2 showed significant antibacterial activity against different plant pathogenic bacteria. The MIC values of P. syringae, X. campestris and X. campestris pv. jugiandis were 7·5, 30 and 15·0 μg ml−1 respectively. Conclusions: Actinomyces A217 fermentation products have a broad spectrum of bacteriostasis, and have good bacteriostasis activity to many plant pathogenic fungi and bacteria. Significance and Impact of the Study: The present study revealed a new antimicrobial producing strain of Streptomyces and its potential application as a biological control agent for plant diseases. [ABSTRACT FROM AUTHOR]

Context Obesity, type 2 diabetes, and dental caries are all major public health problems in the United Kingdom and contribute substantially to healthcare costs. Objective A systematic review and meta-analysis was conducted to determine the effect of product reformulation measures on sugar intake and health outcomes. Data sources Using a combination of terms, the following databases were searched—The Cochrane Library, EMBASE, MEDLINE (Ovid), and Scopus. Additionally, multiple gray literature searches were undertaken. Data extraction A total of 16 studies met the inclusion criteria. There were 4 randomized controlled trials, 6 studies that modeled reformulation in a country, 5 studies that modeled a different approach of reformulation, and 1 study was both a modelling study of a different approach to reformulation and a retrospective observational study. The studies were assessed for risk of bias and overall quality of evidence was rated using the Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE) framework. Results Results from randomized controlled trials suggest that consumption of reformulated products can reduce sugar intake and body weight. The pooled estimates were −11.18% (95% confidence interval [CI], −19.95 to −2.41; P < 0.00001) for changes in percentage of sugar intake, −91.00 g/day (95%CI, −148.72 to −33.28; P< 0.00001) for changes in sugar intake in grams per day, and −1.04 kg (95%CI, −2.16 to −0.08; P= 0.0002) for changes in body weight. However, the quality of the evidence was very low. Results from the other studies suggested that reformulation can reduce sugar intake and improve health. Much of the evidence draws on modeling studies. Conclusions This systematic review and meta-analysis suggests that product reformulation to reduce sugar content could reduce sugar intake in individuals and thus improve population health. These findings provide an important starting point for ongoing work on sugar reformulation. [ABSTRACT FROM AUTHOR]

Background: Several cohort studies with inaccurate estimates of sodium reported a J-shaped relationship with mortality. We compared various estimated sodium intakes with that measured by the gold-standard method of multiple non-consecutive 24-h urine collections and assessed their relationship with mortality.Methods: We analysed the Trials of Hypertension Prevention follow-up data. Sodium intake was assessed in four ways: (i) average measured (gold standard): mean of three to seven 24-h urinary sodium measurements during the trial periods; (ii) average estimated: mean of three to seven estimated 24-h urinary sodium excretions from sodium concentration of 24-h urine using the Kawasaki formula; (iii) first measured: 24-h urinary sodium measured at the beginning of each trial; (iv) first estimated: 24-h urinary sodium estimated from sodium concentration of the first 24-h urine using the Kawasaki formula. We included 2974 individuals aged 30-54 years with pre-hypertension, not assigned to sodium intervention.Results: During a median follow-up of 24 years, 272 deaths occurred. The average sodium intake measured by the gold-standard method was 3769 ± 1282 mg/d. The average estimated sodium over-estimated the intake by 1297 mg/d (95% confidence interval: 1267-1326). The average estimated value was systematically biased with over-estimation at lower levels and under-estimation at higher levels. The average measured sodium showed a linear relationship with mortality. The average estimated sodium appeared to show a J-shaped relationship with mortality. The first measured and the first estimated sodium both flattened the relationship.Conclusions: Accurately measured sodium intake showed a linear relationship with mortality. Inaccurately estimated sodium changed the relationship and could explain much of the paradoxical J-shaped findings reported in some cohort studies. [ABSTRACT FROM AUTHOR]

Abstract: Aims: We sought to isolate novel heterotrophic nitrifying and aerobic denitrifying Klebsiella pneumoniae and Klebsiella variicola strains from various natural environments and characterize their nitrogen removal processes. Methods and Results: Ten novel Klebsiella strains with heterotrophic nitrification and aerobic denitrification abilities, including seven K. pneumoniae and three K. variicola, were successfully isolated from faeces, sewage, plant surfaces and sludge. A 1674‐bp fragment of the hydroxylamine oxidase (hao) gene was successfully amplified from the novel strains. The removal rates of ammonium, nitrate and nitrite of the seven K. pneumoniae isolates were 96·42–97·38%, 61·27–82·78% and 100%, respectively, and the corresponding degradation ratios were 4·82–6·49 (higher than previously reported for K. pneumoniae CF‐S9 and EGD‐HP19‐C), 1·15–1·38 and 1·48–3·33 mg l−1 h−1, respectively. The removal rates of ammonium, nitrate and nitrite of the three K. variicola isolates were 95·01–96·15%,68·60––78·37% and 100%, respectively, and the corresponding degradation ratios were 4·79–9·5, 1·14–1·74 and 1·67–4·44 mg l−1 h−1, respectively. The K. variicola strain sd‐3 from sludge exhibited the best heterotrophic nitrification and aerobic denitrification abilities among the isolates. Meanwhile, the results of simultaneous nitrification and denitrification assays with all isolated strains showed that ammonium was removed prior to nitrate or nitrite. Conclusions: Our results indicate that K. pneumoniae and K. variicola (isolated from a novel natural environment) play an important role in the Earth's nitrogen cycle in various natural environments. Significance and Impact of the Study: This study is one of only a few works to successfully isolate K. pneumoniae with heterotrophic nitrification and aerobic denitrification abilities in various natural environments. The physiological characterization K. variicola as having abilities to heterotrophically nitrify and aerobically denitrify is the first to be reported. Moreover, this study may provide alternative microbial resources for the removal of nitrogen from wastewater. [ABSTRACT FROM AUTHOR]

Aims To evaluate the effect of carabrone on mitochondrial respiratory chain complexes in Gaeumannomyces graminis to identify carabrone targets. Methods and Results The influence of carabrone on mitochondria in G. graminis mycelia was determined, and the activity of complexes I-V, citrate synthase, and respiratory chain complexes I+ III and II+ III was evaluated following treatment with 30% effective concentration ( EC30) as well as EC50 and EC70 of carabrone for 0, 6, 12 and 24 h. Quantitative real-time PCR analysis of the relative expression of genes encoding mitochondrial respiratory chain complexes was then conducted. Carabrone treatment influenced the activity of mitochondrial respiratory chain complexes III, I+ III, and II+ III in G. graminis in a dose- and time-dependent manner with a marked decrease ( c. 50% compared to the control) in mitochondrial respiratory chain complex III activity following treatment with carabrone at the EC50. The GgCyc1 was downregulated following carabrone treatment at the EC50, and the other genes were upregulated with respect to the control. Conclusions This study showed that mitochondrial respiratory chain complex III in G. graminis is highly sensitive to carabrone and is a potential target of this botanical fungicidal agent. Significance and Impact of the Study Carabrone is a promising botanical fungicidal agent that is environmentally friendly and can control plant diseases and reduce chemical fungicides in agricultural production. [ABSTRACT FROM AUTHOR]

In the present study, a 2-stage solid-state fermentation process using Bacillus subtilis followed by Enterococcus faecium was performed with the purpose of improving the nutritional quality of corn and soybean meal (SBM) mixed feed (MF). The matrix of native MF and fermented MF (FMF) was analyzed using scanning electron microscopy to determine external structures after solid-state fermentation. Results of the present study indicated that the FMF had a greater concentration of CP and total P compared with the unfermented feed, whereas the contents of β-conglycinin, glycinin, phytate P, raffinose, stachyose, and NDF in FMF declined by 77.6, 86.7, 41.2, 47.2, 36.6, and 38.9%, respectively. The content of trichloroacetic acid-soluble protein, particularly those of small peptides and free AA, increased more than 3 times after fermentation. Scanning electron microscopy revealed that irregular shapes and a lot of porous structures were observed in the SBM of FMF, the cell wall of corn in FMF was destroyed, and the number of starch granules was decreased after 2-stage fermentation. Two animal experiments were conducted to evaluate the digestibility of CP and P in FMF when fed to pigs. In Exp. 1, 6 barrows (15.20 ± 1.27 kg initial BW) fitted with a T-cannula in the distal ileum were allotted to a replicated 3 x 3 Latin square with 3 diets and 3 periods per square. Two diets containing unfermented MF or FMF as the only source of protein and a N-free diet were formulated. Results indicated that the apparent ileal digestibility (AID) of total AA and Lys in FMF (74.98 and 75.34%) were greater (P < 0.05) than in untreated MF (69.66 and 68.56%). The standard ileal digestibility (SID) of Lys in FMF (82.17%) was also greater (P < 0.05) than in MF (75.91%). In Exp. 2, 16 barrows (17.57 ± 1.08 kg initial BW) were allotted to 2 diets formulated to contain MF or FMF as the sole source of P to determine the digestibility of P. The apparent total tract digestibility and standardized total tract digestibility of P in FMF were 58.14 and 64.72%, respectively. These values were greater (P < 0.01) than in untreated MF (37.11 and 44.89%, respectively). Our results indicate that a solid-state fermentation process using B. subtilis followed by E. faecium offers an effective approach to improving the quality of corn and SBM MF. [ABSTRACT FROM AUTHOR]

Background The pathophysiology of lymphoedema is poorly understood. Current treatment options include compression therapy, resection, liposuction and lymphatic microsurgery, but determining the optimal treatment approach for each patient remains challenging. Objectives We characterized skin and adipose tissue alterations in the setting of secondary lymphoedema. Methods Morphological and histopathological evaluations were conducted for 70 specimens collected from 26 female patients with lower-extremity secondary lymphoedema following surgical intervention for gynaecological cancers. Indocyanine green lymphography was performed for each patient to assess lymphoedema severity. Results Macroscopic and ultrasound findings revealed that lymphoedema adipose tissue had larger lobules of adipose tissue, with these lobules surrounded by thick collagen fibres and interstitial lymphatic fluid. In lymphoedema specimens, adipocytes displayed hypertrophic changes and more collagen fibre deposits when examined using electron microscopy, whole-mount staining and immunohistochemistry. The number of capillary lymphatic channels was also found to be increased in the dermis of lymphoedema limbs. Crown-like structures (dead adipocytes surrounded by M1 macrophages) were less frequently seen in lymphoedema samples. Flow cytometry revealed that, among the cellular components of adipose tissue, adipose-derived stem/stromal cells and M2 macrophages were decreased in number in lymphoedema adipose tissue compared with normal controls. Conclusions These findings suggest that long-term lymphatic volume overload can induce chronic tissue inflammation, progressive fibrosis, impaired homeostasis, altered remodelling of adipose tissue, impaired regenerative capacity and immunological dysfunction. Further elucidation of the pathophysiological mechanisms underlying lymphoedema will lead to more reliable therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background The epidemiology of cutaneous herpes simplex infection ( CHSI) has dramatically changed over the past several decades. Valaciclovir is one of a new generation of antiviral medications that has expanded treatment options for the most common cutaneous manifestations of herpes simplex virus. However, the efficacy and safety of formulations with different doses of valaciclovir remain unclear. Aim To carry out hospital risk management by ascertaining the incidence and risk of CHSI in patients during treatment with varying doses of valaciclovir. Methods The PubMed, MEDLINE and Web of Science electronic databases were systematically searched from database inception to date of searching. Efficacy of drug treatment was measured by average easement score ( AES). Safety was characterized as the proportion of patients with drug adverse reactions ( DARs) such as fever, dizziness, headache, anxiety, irritability and yellowing of the skin. Outcomes for continuous and dichotomous data were estimated by standard mean difference ( SMD) and risk ratio ( RR), respectively. Results Five randomized controlled trials involving 1753 randomized participants for efficacy assessment and 1874 randomized participants for safety assessment were identified. Valaciclovir dose increasing from 1000 mg/day improved AES only moderately, but significantly promoted the incidence of DARs. Twice-daily treatment showed no increase in therapeutic effect but greatly increased DAR incidence. The valaciclovir dose that produced a reduction in AES was 1000 mg/day: SMD = −0.73 (95% CI −0.98 to 0.48; P < 0.01) and RR = 0.95 (95% CI 0.81-1.09; P < 0.002). Conclusions Increasing the daily dose of valaciclovir does not substantially improve therapeutic efficacy for CHSI but may raise DAR incidence. Drug doses of 1000 and 2000 mg/day show no significant difference in efficacy scores, but the latter exhibits a higher incidence of DARs. The dose-dependent, long-term efficacy and safety of valaciclovir remain to be explored. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effects of immunological challenge on the skeletal muscle fiber type conversion of piglets. Sixteen Large White weaned barrows (28 ± 3 d, 8.22 ± 0.89 kg BW) were allotted by weight and litter to 2 groups: the control group and the lipopolysaccharide (LPS) group. Saline (control) or LPS was injected intravenously via a jugular catheter on d 1, 3, 5, 7, 9, 11, 13, and 15 at an initial dosage of 80 μg/kg BW, which was increased by 30% at each subsequent injection. Blood samples were collected via the jugular catheter 3 h after the LPS challenge on d -1, 1, 5, 9, and 13. Muscle tissue samples were collected from the LM after exsanguination on d 15. The LPS challenge increased the plasma IL-6, tumor necrosis factor-α (TNF-α), cortisol, IL-1β, and haptoglobin concentrations on d 1 and 5 (P < 0.01) and increased the plasma IL-6 (P < 0.05), TNF-α (P < 0.05), and haptoglobin (P < 0.01) levels on d 9. Compared with that of the control group, the ADG of the LPS group decreased by 40.00% (P < 0.01), 29.52% (P < 0.05), and 19.30% (P < 0.05), and the ADFI decreased by 25.09% (P < 0.01), 23.15% (P < 0.05), and 19.47% (P < 0.05) during d 1 to 4, d 5 to 8, and d 9 to 15, respectively. In the LM of LPS-challenged piglets, myosin heavy chain 1 (MyHC1) mRNA and protein expression tended to be reduced (P = 0.08, 0.09), whereas MyHC2x mRNA, MyHC2b mRNA, and MyHC2 protein expression increased (P < 0.05). The LPS challenge reduced succinic dehydrogenase (SDH) activity (P < 0.05) and increased lactate dehydrogenase (LDH) activity (P < 0.05) in the LM of piglets. Compared with those in the control group, transcriptional peroxisome proliferatoractivated receptor coactivator-α (PGC-α) mRNA (P < 0.05), calcineurin (CaN) mRNA, and protein expression were reduced (P < 0.05), and PGC-α protein expression tended to be reduced (P = 0.08) in the LM of LPS-challenged piglets. These results show that immunological challenge induced by LPS resulted in a shift from type I to type II fibers in the LM of piglets, which may be mediated by the downregulation of the CaN/PGC-a signaling pathway. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening condition, but the pathophysiological basis and biomarkers for the monitoring of sepsis and as targets for therapy remain to be determined. We have shown previously that T cell immunoglobulin and mucin domain protein 3 ( Tim-3), a negative immune regulator, is involved in the physiopathology of sepsis, but the underlying mechanisms remain unclear. In the present study, we showed that Tim-3 signalling modulated the response patterns of both macrophages and T helper cells in sepsis. Blockade of the Tim-3 pathway exacerbated sepsis-induced proinflammatory macrophage responses and lymphocyte apoptosis during the early phase of sepsis, and enhanced the shift to anti-inflammatory responses for both macrophages and T helper cells during the late phase of sepsis. Tim-3 signalling was found to regulate CD80 and CD86 expression on macrophages both in vivo and in vitro. Co-culture of T cells with Tim-3 knock-down macrophages led to a biased T helper type 2 ( Th2) response, partially explaining how Tim-3 signalling shapes inflammation patterns in vivo. Further studies on this pathway might shed new light on the pathogenesis of sepsis and suggest new approaches for intervention. [ABSTRACT FROM AUTHOR]

This study aimed to examine the frequency of different subsets of circulating B and T follicular helper ( Tfh) cells in patients with new-onset rheumatoid arthritis ( RA) and following standard therapies. Twenty-five RA patients and 15 healthy controls ( HC) were recruited for characterizing the frequency of CD27+, immunoglobulin ( Ig)D+, CD86+, CD95+, Toll-like receptor ( TLR)-9+ B cells and inducible T cell co-stimulator ( ICOS) and programmed death 1 ( PD-1)-positive Tfh cells and the level of serum interleukin ( IL)-21. The potential correlation between the frequency of different subsets of B and Tfh cells and the values of clinical measures in RA patients was analysed. In comparison with HC, significantly higher percentages of circulating IgD+ CD27− CD19+ naive B, CD86+ CD19+ and CD95+ CD19+ activated B, CD3+ CD4+ CXCR5+, CD3+ CD4+ CXCR5+ ICOS+, CD3+ CD4+ CXCR5+ PD-1+ and CD3+ CD4+ CXCR5+ ICOS+ PD-1+ Tfh cells but lower IgD+ CD27+ CD19+ preswitch memory B cells were detected, accompanied by significantly higher levels of serum IL-21 in the RA patients. Furthermore, the percentages of CD95+ B cells were correlated positively with the frequency of PD-1+ Tfh cells, but negatively with ICOS+ Tfh cells. The percentages of CD86+ B cells and ICOS+ Tfh cells were correlated positively with the values of disease activity score 28 ( DAS28). Following the drug therapies for 1 month, the percentages of CD86+ B and PD-1+ Tfh cells were reduced significantly in the drug-responding patients. Our data suggest that activated B and Tfh cells may contribute to the pathogenesis of RA and the frequency of activated B and Tfh cells may be used as biomarkers for evaluating the therapeutic responses of individual patients with RA. [ABSTRACT FROM AUTHOR]

Background Plasma sodium is increased following each meal containing salt. There is an increasing interest in the effects of plasma sodium concentration, and it has been suggested that it may have direct effects on blood pressure (BP) and possibly influences endothelial function. Experimental increases of plasma sodium concentration rapidly raise BP even when extracellular volume falls. Methods Ten patients with end-stage renal failure established on haemodialysis were studied during the first 2 h of dialysis without fluid removal during this period. They were randomized to receive haemodialysis with (i) dialysate sodium concentration prescribed to 135 mmol/L and (ii) 145 mmol/L in random order in a prospective, single-blinded crossover study. BP measurements and blood samples were taken every 30 min. Results Pre-dialysis sitting BP was 137/76 ± 7/3 mmHg. Lower dialysate sodium concentration (135 mmol/L) reduced plasma sodium concentration [139.49 ± 0.67 to 135.94 ± 0.52 mmol/L (P < 0.001)], whereas plasma sodium concentration was not altered by higher dialysate sodium (145 mmol/L) (140.17 ± 0.66 mmol/L at baseline to 140.72 ± 0.43 mmol/L at 120 min). Systolic BP was lower with dialysate sodium concentration 135 mmol/L [area under the curve (AUC) 15823.50 ± 777.15 (mmHg)min] compared with 145 mmol/L [AUC 17018.20 ± 1102.17 (mmHg)min], mean difference 1194.70 ± 488.41 (mmHg)min, P < 0.05. There was a significant positive relationship between change in plasma sodium concentration and change in systolic BP. This direct relationship suggests that a fall of 1 mmol/L in plasma sodium concentration would be associated with a 1.7 mmHg reduction in systolic BP (P < 0.05). Conclusions The potential mechanism for the increase in BP seen with salt intake may be through small but significant changes in plasma sodium concentration. [ABSTRACT FROM AUTHOR]

There is much evidence for a causal relationship between salt intake and blood pressure (BP). The current salt intake in many countries is between 9 and 12 g/day. A reduction in salt intake to the recommended level of 5–6 g/day lowers BP in both hypertensive and normotensive individuals. A further reduction to 3–4 g/day has a much greater effect. Prospective studies and outcome trials have demonstrated that a lower salt intake is associated with a decreased risk of cardiovascular disease. Increasing evidence also suggests that a high salt intake is directly related to left ventricular hypertrophy (LVH) independent of BP. Both raised BP and LVH are important risk factors for heart failure. It is therefore possible that a lower salt intake could prevent the development of heart failure. In patients who already have heart failure, a high salt intake aggravates the retention of salt and water, thereby exacerbating heart failure symptoms and progression of the disease. A lower salt intake plays an important role in the management of heart failure. Despite this, currently there is no clear evidence on how far salt intake should be reduced in heart failure. Our personal view is that these patients should reduce their salt intake to <5 g/day, i.e. the maximum intake recommended by the World Health Organisation for all adults. If salt intake is successfully reduced, there may well be a need for a reduction in diuretic dosage. [ABSTRACT FROM PUBLISHER]

Epidermolysis bullosa (EB) pruriginosa, characterized by severe itching and the presence of nodular prurigo-like or lichenoid lesions, is a rare clinical type of dystrophic EB. Mutations in the COL7A1 gene encoding type VII collagen, the major component of anchoring fibrils, have been implicated in the pathogenesis of the disorder. In the present study, we screened a Chinese family with EB pruriginosa for COL7A1 mutations by PCR amplification of genomic sequences and direct nucleotide sequencing. The mutation consists of a G→T substitution at nucleotide 6724 in exon 85, which leads to the substitution of glycine by tryptophan at codon 2242. This report adds new variants to the known COL7A1 mutations underlying EB pruriginosa, and provides the basis for genetic counselling and prenatal diagnosis for affected families. [ABSTRACT FROM AUTHOR]

Aims: To clone and characterize genes encoding novel cellulases from metagenomes of buffalo rumens. Methods and Results: A ruminal metagenomic library was constructed and functionally screened for cellulase activities and 61 independent clones expressing cellulase activities were isolated. Subcloning and sequencing of 13 positive clones expressing endoglucanase and MUCase activities identified 14 cellulase genes. Two clones carried two gene clusters that may be involved in the degradation of polysaccharide nutrients. Thirteen recombinant cellulases were partially characterized. They showed diverse optimal pH from 4 to 7. Seven cellulases were most active under acidic conditions with optimal pH of 5·5 or lower. Furthermore, one novel cellulase gene, C67-1, was overexpressed in Escherichia coli, and the purified recombinant enzyme showed optimal activity at pH 4·5 and stability in a broad pH range from pH 3·5 to 10·5. Its enzyme activity was stimulated bydl-dithiothreitol. Conclusions: The cellulases cloned in this work may play important roles in the degradation of celluloses in the variable and low pH environment in buffalo rumen. Significance and Impact of the Study: This study provided evidence for the diversity and function of cellulases in the rumen. The cloned cellulases may at one point of time offer potential industrial applications. [ABSTRACT FROM AUTHOR]

Background: Cell adhesion molecules have been implicated to be up-regulated in systemic vasculitis and could be potentially used as clinical diagnostic biomarkers. As a newly identified adhesion molecule, the expression level of CD146 in vasculitis has never been determined.Methods: Clinical samples were collected and levels of soluble CD146 were measured in sera using sandwich ELISA and neutrophil CD146 using FACS analysis in 59 patients with active systemic vasculitis and 34 healthy controls.Results: Expression of CD146 was significantly elevated in circulating neutrophils of patients with active small-vessel vasculitis (WG and MPA), but not in patients with large-vessel vasculitis (TA), compared with samples from healthy controls. Interestingly, elevated levels of neutrophil CD146 were dramatically decreased after treatment with immunosuppressive drugs. Moreover, a significantly increased level of soluble CD146 was found in sera from patients with MPA and vasculitis-induced renal failure.Conclusion: The clinical study indicated that CD146 expression was elevated in active vasculitis and correlated with its pathological progression and post-treatment remission. [ABSTRACT FROM AUTHOR]

An editorial is presented which comments on a paper about the health aspects of salt. The authors argue against the accusation that they restricted potassium intake during the randomized double-blind crossover trials of modest salt restriction. They mention the results of the Dietary Approaches to Stop Hypertension (DASH)-Sodium study. They explain the commercial interest of the salt industry.

Adipose triglyceride lipase (ATGL) was recently identified and described as a major novel triglyceride lipase in animals. In this study, we aimed to study the tissue-specific and developmental expression pattern of porcine ATGL (pATGL) and the effect of resveratrol (RES) on expression of pATGL in vitro. The full-length cDNA sequence of pATGL was 1,958 bp (accession no. EF583921), with a 1,458-bp open reading frame encoding a 486-AA protein (the predicted molecular mass of 53.2 kDa, accession no. ABS58651). Comparison of the deduced AA sequence with the bovine, mouse, rat, dog, and human adipose triglyceride lipase showed 87, 84, 83, 81, and 80% similarity, respectively. Furthermore, the pATGL was highly ex- pressed in porcine adipose tissue, to a lesser degree in kidney, heart, and muscle, and least but detectable in brain. In s.c. adipose tissue, pATGL mRNA was low at birth (1 kg of BW) and then increased, reaching a maximal value at 20 kg of BW (approximately 8 wk old; P < 0.01). In peritoneal and omental adipose tissue, the greatest expression of pATGL was observed at 40 kg of BW (approximately 12 wk old). In vitro, exposure of cultured adipocytes to 40 and 80 μM RES for 24 h increased the mRNA levels of pATGL by 95.3% (P< 0.05) and 146.8% (P < 0.01), respectively. Accordingly, lipid accumulation was decreased by 25.7% (P < 0.05) and 60.8% (P < 0.01), respectively. When treated with RES for 48 h, the mRNA levels of pATGL were increased by 104.1% (P < 0.05) and 163.1% (P < 0.01), respectively. As expected, lipid accumulation was decreased by 9.7% (P> 0.05) and 29.0% (P < 0.05), respectively. These results add to our understanding of the role of pATGL in adipose tissue development and as a potential target for regulating fat deposition and meat quality. [ABSTRACT FROM AUTHOR]

Aim: In the early stages of hypertension (HTN), when global left ventricular (LV) function is still unaffected, localized geometrical changes suggest changes in regional function. We investigated regional geometry and systolic deformation (using strain/strain rate (S/SR) imaging) in HTN. [ABSTRACT FROM PUBLISHER]

Aims: To evaluate the influence of environmental parameters on the production of antibiotics (xenocoumacins and nematophin) by Xenorhabdus nematophila and enhance the antibiotic activity. Methods and Results: Response surface methodology (RSM) was employed to study the effects of five parameters (the initial pH, medium volume in flask, rotary speed, temperature and inoculation volume) on the production of antibiotics in flask cultures by X. nematophila YL001. A 25−1-factorial central composite design was chosen to explain the combined effects of the five parameters and to design a minimum number of experiments. The experimental results and software-predicted values of production of antibiotics were comparable. The statistical analysis of the results showed that, in the range studied, medium volume in flask, rotary speed, temperature and inoculation volume had a significant effect ( P < 0·05) on the production of antibiotics at their individual level, medium volume in flask and rotary speed showed a significant influence at interactive level and were most significant at individual level. The maximum antibiotic activity was achieved at the initial pH 7·64, medium volume in 250 ml flask 25 ml, rotary speed of 220 rev min−1, temperature 27·8°C and inoculation volume of 15·0%. Maximum antibiotic activity of 331·7 U ml−1 was achieved under the optimized condition. Conclusions: As far as known, there are no reports of production of antibiotic from X. nematophila by engineering the condition of fermentation using RSM. The results strongly support the use of RSM for fermentation condition optimization. The optimization of the environmental parameters resulted not only in a 43·4% higher antibiotic activity than unoptimized conditions but also in a reduced amount of the experiments. The chosen method of optimization of fermentation condition was efficient, relatively simple and time and material saving. Significance and Impact of the Study: This study should contribute towards improving the antibiotics activity of X. nematophila. Integrated into a broader study of the impact of environmental factors on the production of antibiotic, this work should help to build more rational control strategy, possibly involving scale-up of production of antibiotics by X. nematophila. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the effect of Nidus Vespae extract and chemical fractions on the viability and architecture of Streptococcus mutans biofilms. Methods and Results: The raw material was first extracted using 95% ethanol/water. Subsequent fractions were prepared from this extract using cyclohexane/ethyl acetate, petroleum ether/ethyl acetate and chloroform/methanol. The biomass dry weight and total protein of samples treated with Nidus Vespae extract and chemical fractions were significantly less than those treated with the vehicle control ( P < 0·05). Biofilms treated with Nidus Vespae also resulted in lower percentage of polysaccharide composition. The pH decrease in the biofilm matrix was retarded by Nidus Vespae compared with the vehicle control. Architecture of biofilms treated with Nidus Vespae was different than in the vehicle control and 0·05% chlorhexidine. Conclusions: Chloroform/methanol fraction was the most effective treatment. Significance and Impact of the Study: The significant antibiofilm activity demonstrated by Nidus Vespae shows it to be a promising source of novel anticariogenic agents. [ABSTRACT FROM AUTHOR]

A total of 90 weaned female pigs (Duroc x Landrace x Yorkshire) were used in a 15-d growth experiment to investigate the effect of lactoferrin on growth performance, intestinal morphology, and expression of PR-39 and protegrin-1 genes. The pigs were allocated on the basis of BW and litter to 3 dietary treatments in a randomized complete block design. There were 3 replicate pens per treatment, and the pigs were grouped with 10 pigs per pen. The dietary treatments were (1) basal diet; (2) basal diet + 20 mg of flavomycin/kg + 110 mg of aureomycin/kg; (3) basal diet + 1.0 g of lactoferrin/kg. Six pigs, randomly selected from each treatment (2 piglets/pen) were slaughtered for intestinal morphology and expression of PR-39 and protegrin-1 genes at the end of the experiment. Supplementation with lactoferrin improved growth performance; it increased ADG by 41.80% (P < 0.01) and efficiency of gain (G:F) by 17.20% (P < 0.05). Intestinal villus height was increased by 15.30% (P < 0.05), and crypt depth was decreased by 9.60% (P < 0.05). Supplemental lactoferrin increased the relative abundance of mRNA for PR-39 and protegrin-1 by 143% (P < 0.01) and 217% (P < 0.01), respectively. The use of lactoferrin as an additive to improve nonspecific immunity and strengthen host defenses would be good a method of defending weaned pigs from infections and weanling stress. [ABSTRACT FROM AUTHOR]

Examines the phylogenetic relationship between dwarf blue sheep and blue sheep based on the mitochondrial DNA control region and nuclear Y-linked ZFY intron sequences. Haplotypes found in blue sheep and dwarf blue sheep; Analyses of the ZFY intron sequences; Genetic distinctiveness of dwarf blue sheep; Differentiation between blue sheep and dwarf blue sheep based on the ZFY intron data.

Different DNA-damaging treatments produce a senescence-like phenotype. Young human fibroblasts are transferred to a senescence-like state after 4 to 6 weeks of culture under 40% ambient oxygen partial pressure. In order to understand the causes of senescence it would be advantageous to know how well this state equals accelerated senescence. Therefore, we measured the expression of genes with known senescence-specific expression pattern in human fibroblasts, which were irreversibly proliferation-inhibited by chronic hyperoxic treatment. A senescence-specific gene expression pattern was confirmed by semiquantitative RT-PCR for eight out of nine examined genes in BJ foreskin fibroblasts and for four out of four genes in MRC-5 lung fibroblasts. For all these cases, gene expression under hyperoxia was similar to that in senescent cells, suggesting that chronic mild hyperoxia is a valid model for accelerated senescence. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Normal Range of Human Dietary Sodium Intake: A Perspective Based on 24-Hour Urinary Sodium Excretion Worldwide" by DA McCarron, AG Kazaks, JC Geerling, JS Stern, and NA Graudal in volume 26 of this journal.

The article discusses a study on the correlation of positive parental attitudes towards adolescent indoor tanning in the U.S. The study suggests that a family history of skin cancer and provider counselling influence parents' attitudes about adolescent indoor tanning. It also suggests that the association between parents' own indoor tanning use and their attitudes toward adolescents' use is consistent with a family-centred approach to indoor tanning prevention.

A previously undescribed missense mutation was detected in the L12 domain of keratin 5 (K5) in a Chinese family with Weber–Cockayne epidermolysis bullosa simplex. Direct sequencing of the PCR products identified a single base substitution (983A→G) that changes the aspartic acid residue at codon 328 to glycine in all affected family members, while no mutation was observed either in the healthy individual or 50 unrelated control samples. Asp328 of K5 is remarkably conserved among all type II keratins. D328G is the fourth mutation found to affect this residue in K5-related epidermolysis bullosa simplex, indicating the importance of Asp328 for K5 structure and the dramatic effect that fine changes can have on keratin intermediate filament integrity. [ABSTRACT FROM AUTHOR]

This experiment was conducted to investigate how betaine affect muscle lipid metabolism. A total of 120 crossbred gilts (Landrace × Yorkshire × Duroc) with an initial BW of 70.07 kg (SD 0.70 kg) were randomly allocated into 3 treatments. Pigs were fed a corn-soybean meal basal diet supplemented with betaine at 0, 1,250, or 2,500 mg/kg, respectively. The feeding experiment lasted 42 d after a 7-d adaptation period. At the end of the trial, 18 pigs (6 from each dietary treatment) were euthanized and individual blood samples were collected and samples of LM between the 6th and 7th rib were obtained on the left side of the carcass. All data were analyzed using 1-way ANOVA of SAS 9.1. The results showed that betaine significantly increased the concentration of free fatty acid (FFA) in muscle (P < 0.05) and numerically decreased serum FFA (P > 0.05). Furthermore, the levels of serum cholesterol and high-density lipoprotein cholesterol were decreased (P < 0.05) whereas total cholesterol content was increased in muscle (P < 0.05) with dietary betaine supplementation. Experiments about key factors involved in fatty acid transportation showed that the gene expression of lipoprotein lipase, fatty acid translocase/cluster of differentiation (FAT/CD36), fatty acid binding protein (FABP3), and fatty acid transport protein (FATP1) were significantly increased with betaine supplementation (P < 0.05). Besides, the protein expressions of FATP1 and FABP3 were enhanced as well (P < 0.05). As for the key factors involved in fatty acid oxidation, although the level of carnitine and malony-CoA in muscle were not affected, both gene expression and protein expression of carnitine palmitransferase-1 (CPT1) were significantly increased with betaine supplementation (P < 0.05). Additionally, the gene expression of AMPKα2 and PPARα as well as the protein expression of p-AMPK was increased (P < 0.05). The results suggest that betaine supplementation could promote fatty acid uptake in the muscle and enhance fatty acid oxidation, leading to an increase of fatty acids in muscle. [ABSTRACT FROM AUTHOR]

An abstract of the article “Homozygous 5T Alleles, Clinical Presentation and Genetic Analysis Within a Family With Congenital Bilateral Absence of the Vas Deferens (CBAVD)" by J. Feng, Y. Zhang, and X. Wu is presented.

Extended abstract of a paper presented at Microscopy and Microanalysis 2011 in Nashville, Tennessee, USA, August 7–August 11, 2011. [ABSTRACT FROM PUBLISHER]

A letter to the editor is presented in response to the article "Compared with usual sodium intake, low- and excessive-sodium diets are associated with increased mortality: a meta-analysis," N. Graudal and colleagues in the 2014 issue.

The article presents a study to determine clinical findings in azooaspermic men with a congenital unilateral absence of the vas deferens (CUAVD) and contralateral palpable scrotal vas deferens and its treatment. The article discusses the retrospective review of their clinical findings and the patency of contralateral vas deferens was evaluated with an injection of diluted methylene blue. It concludes that the rate of distal obstruction is high in CUAVD patients.

The article discusses proteomic analysis of rat testis in experimental varicocoele and the function of heterogeneous nuclear ribonucleoprotein F in germ cell apoptosis. Topics discussed include experimental varicocele induced by partial ligation of the left renal vein of rats, applying proteomics technology to determine the altered proteins, and detecting expression and location in germ cell.

The article presents an abstract on vasal vessels preserving microsurgical Vasoepididymostomy (VE) and its popularity in treating epididymal obstructive azoospermia including the complications in patients who have undergone VE.