Background To determine the most significant potentially actionable clinical variables associated with mortality and hospitalization risk in hemodialysis (HD) patients. Study Design Cohort study. ...Setting & Participants Adult maintenance HD patients in the Fresenius Medical Care, North America database as of January 1, 2004, with baseline information from October 1, 2003, to December 31, 2003, comprising approximately 26% of the US HD population. Predictors Case-mix (age, sex, race, diabetes, vintage, and body surface area), vascular access, and laboratory (albumin, equilibrated Kt/V, hemoglobin, calcium, phosphorus, creatinine, bicarbonate, biointact parathyroid hormone, transferrin saturation, and white blood cell count) variables. Outcomes 1-year mortality and hospitalization risk from January 1 to December 31, 2004. Measurements Cox proportional hazards models for death and hospitalization. Results The cohort (N = 78,420) had a mean age of 61.4 ± 15.0 years, 47% were women, 49% were white, 41% were black race (10% defined as “other”), and 52% had diabetes. The top 5 actionable variables were the same for mortality and hospitalization. Final case-mix plus laboratory–adjusted hazard ratios for these top 5 actionable variables indicate 177% increased risk of death and 67% increased risk of hospitalization per 1-g/dL decrease in albumin level, 39% and 45% greater risk with catheters compared with fistulas, 18% and 9% greater risk per 1-mg/dL greater phosphorus level, 11% and 9% lower risk per 1-g/dL greater hemoglobin level, and 5% and 2% greater risk per 0.1-unit decrease in equilibrated Kt/V, respectively (all P < 0.0001). Limitations Observational cross-sectional study with limited comorbidity adjustment (for diabetes). Conclusion The same variables are associated with both mortality and hospitalization in HD patients. The top 5 potentially actionable variables are readily identifiable, with albumin level and catheter use the most prominent, and all 5 are appropriate targets for improvement.
Ischemia reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI) in both native and transplanted kidneys. The objective of the present study was to evaluate whether ...low-molecular-weight fucoidan (LMWF) could attenuate renal IRI in an animal model and in vitro cell models and study the mechanisms in which LMWF protected from IRI.
Male mice were subjected to right renal ischemia for 30 min and reperfusion for 24 h, or to a sham operation with left kidney removed. Kidneys undergone IR showed characteristic morphological changes, such as tubular dilatation, and brush border loss. However, LMWF significantly corrected the renal dysfunction and the abnormal levels of MPO, MDA and SOD induced by IR. LMWF also inhibited the activation of MAPK pathways, which consequently resulted in a significant decrease in the release of cytochrome c from mitochondria, ratios of Bax/Bcl-2 and cleaved caspase-3/caspase-3, and phosphorylation of p53. LMWF alleviated hypoxia-reoxygenation or CoCl(2) induced cell viability loss and ΔΨm dissipation in HK2 renal tubular epithelial cells, which indicates LMWF may result in an inhibition of the apoptosis pathway through reducing activity of MAPK pathways in a dose-dependent manner.
Our in vivo and in vitro studies show that LMWF ameliorates acute renal IRI via inhibiting MAPK signaling pathways. The data provide evidence that LMWF may serve as a potential therapeutic agent for acute renal IRI.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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•Oblique flows alleviate the inhibited downstream growth at low undercoolings.•The melt flow inhibits upstream primary branches of columnar dendrites.•Secondary arms are firstly more ...developed at left sides of primary branches.•Flows do more significant effects under lower undercooling or cooling conditions.
A cellular automaton (CA) model coupled with momentum, mass and heat transport models was developed to investigate equiaxed and columnar dendritic growth of Fe–0.82wt%C alloy under four elaborately designed forced flows. During the iterative solution, the evolution of solidification interface and the solute diffusion in solid phase were explicitly tracked and solved, while other transport equations were implicitly solved in staggered grids with the block-corrected TDMA approach. The self-developed codes show a good performance in predicting dendritic growth and melt flow and temperature fields according to the comparisons with LGK analytical model and commercial software. The growth behavior of dendrites under melt flow is determined by the competition between bringing in solute enriched melt from upstream side and carrying away solute rejected at interfaces. The growth of equiaxed dendrites is promoted at the upstream side and inhibited at the downstream side, which becomes more significant with the increase of inlet velocity and the decrease of melt undercooling. Meanwhile, the oblique flow plays an important role in the growth of arms at the downstream side and alleviates the inhibited growth at the lower melt undercooling. Columnar dendrites are under inhibited growth in sequence along the flow direction, except that those near the outlet are promoted under weaker melt flow. Secondary dendrite arms firstly well formed at left sides of columnar dendrites become fatter and better developed compared with those without flow, although those near the upstream side are difficult to be developed. Under the circular flow condition, columnar dendrites at the bottom wall of the modeling domain firstly grow faster than those symmetrically in the right wall, and then become slower as the solidification proceeds under stronger melt flow. Moreover, the effect of melt flow on dendritic growth becomes more significant under the lower melt undercooling condition for equiaxed dendrites and the weaker cooling condition for columnar dendrites. In addition, compared with the effect on the temperature distribution, the effect of the melt flow on the solute distribution around columnar dendrites governs their growth.
Heat stress is an important factor affecting soybean yield. Brassinosteroids (BRs) play a crucial role in plant growth, development, and defense. In the present study, the regulatory effects of ...24-epibrassinolide (EBR, one of the bioactive BRs) on heat tolerance in soybeans, and its underlying physiological mechanisms were investigated. The results show that foliar spraying with EBR significantly alleviate heat stress-induced water loss and oxidative damage in soybean leaves. The activities of antioxidant enzymes (superoxide dismutase, catalase, and peroxidase) and the contents of antioxidant substances (ascorbic acid and reduced glutathione) were markedly increased in EBR-treated leaves compared with water-treated leaves, which contributed to maintaining reactive oxygen species homeostasis and relieving oxidative injury under heat stress. However, EBR-treated leaves showed a significant decrease in free proline and total soluble sugar content under heat stress compared to water-treated leaves. In addition, EBR treatment showed obviously higher photosystem II activity under heat stress, and higher net photosynthetic rate and biomass accumulation after recovery from heat stress compared to water treatment. Collectively, these results indicated that EBR could significantly improve the capacity of antioxidant defense systems to protect photosynthetic apparatus under heat stress, thereby effectively alleviating heat stress-induced growth inhibition in soybean plants.
Diminished ovarian reserve (DOR) contributes significantly to female infertility. Bushen Cuyun Recipe (BCR, Tradename Yueliang Yin), a product marketed in China, has shown effects in the treatment of ...female infertility in clinical practices of traditional Chinese medicine (TCM). In this study, we aimed to investigate the chemical compositions of BCR and its efficacy based on scientific evidence and pharmacological mechanisms in DOR treatments.
The chemical compositions of BCR were determined by the UHPLC-LTQ-Orbitrap MS method. DOR was induced in a rat model by intraperitoneal injection of cyclophosphamide (CTX) 90 mg/kg once. After the CTX treatment for 14 days, rats were intragastrically administrated deionized water, dehydroepiandrosterone (DHEA), or BCR in low, middle, and high doses for 30 days. Ovarian index, ovarian morphology, follicle number, and anti-Müllerian hormone (AMH) in serum were determined to assess the effects of BCR. To investigate possible action mechanisms, network pharmacological analysis was used to predict possible pathways in the effects of BCR on female infertility. In experimental studies, the contents of hormones in the hypothalamic-pituitary-ovarian axis (HPOA, including estradiol (E
), follicle-stimulating hormone (FSH), and gonadotropin-releasing hormone (GnRH)) and pyroptosis-related proteins, including gasdermin D (GSDMD), caspase-1, and interleukin-18 (IL-18), in ovarian were detected by ELISA, immunofluorescence and Western blot.
Chemical studies revealed a total 84 components in BCR, which included 43 flavonoids, 13 triterpenoids, 11 phenolic acids, 8 alkaloids, 1 coumarin, 1 anthraquinone, and 7 other components. After treatments with BCR, the ovarian morphology, ovarian index, estrous cycle, growing follicles and corpus luteum from last ovulation, and serum AMH in DOR rats were significantly improved. Network pharmacological analysis suggested that the NOD-like receptor signaling pathway ranked No. 1 among the mechanisms by which BCR affects female infertility. Experimental results demonstrated that the content of serum FSH in DOR rats was significantly decreased and the contents of serum GnRH and E
were significantly elevated after BCR treatment and that the elevated level of GSDMD, caspase-1, and IL-18 was significantly reversed in BCR-treated rats.
The chemical compositions of BCR were first identified in the present study. BCR was demonstrated to show protective effects on DOR. The possible mechanisms of BCR on DOR might be mediated by regulating gonadal hormones of the HPOA and protecting granulosa cells in ovary against pyroptosis.
Tillering is an important biomass yield component trait in switchgrass (
.).
(
)/
(
) gene is a known regulator for tillering/branching in several plant species; however, its role on tillering in ...switchgrass remains unknown. Here, we report physiological and molecular characterization of mutants created by CRISPR/Cas9. We successfully obtained nonchimeric
and
mutants from chimeric T0 mutants using nodal culture. The biallelic
mutant plants produced significantly more tillers and higher fresh weight biomass than the wild-type plants. The increased tiller number in the mutant plants resulted primarily from hastened outgrowth of lower axillary buds. Increased tillers were also observed in transgene-free BC1 monoallelic mutants for either
or
gene alone, suggesting
genes act in a dosage-dependent manner. Transcriptome analysis showed 831 genes were differentially expressed in the
a-
double knockdown mutant. Gene Ontology analysis revealed downregulation of
genes affected multiple biological processes, including transcription, flower development, cell differentiation, and stress/defense responses in edited plants. This study demonstrates that
genes play a pivotal role in tiller production as a negative regulator in switchgrass and provides opportunities for further research aiming to elucidate the molecular pathway regulating tillering in switchgrass.
Urea transporters (UT) are a family of transmembrane urea-selective channel proteins expressed in multiple tissues and play an important role in the urine concentrating mechanism of the mammalian ...kidney. UT inhibitors have diuretic activity and could be developed as novel diuretics. To determine if functional deficiency of all UTs in all tissues causes physiological abnormality, we established a novel mouse model in which all UTs were knocked out by deleting an 87 kb of DNA fragment containing most parts of Slc14a1 and Slc14a2 genes. Western blot analysis and immunofluorescence confirmed that there is no expression of urea transporter in these all-UT-knockout mice. Daily urine output was nearly 3.5-fold higher, with significantly lower urine osmolality in all-UT-knockout mice than that in wild-type mice. All-UT-knockout mice were not able to increase urinary urea concentration and osmolality after water deprivation, acute urea loading, or high protein intake. A computational model that simulated UT-knockout mouse models identified the individual contribution of each UT in urine concentrating mechanism. Knocking out all UTs also decreased the blood pressure and promoted the maturation of the male reproductive system. Thus, functional deficiency of all UTs caused a urea-selective urine-concentrating defect with little physiological abnormality in extrarenal organs.
According to traditional Chinese veterinary medicine, endometritis is caused by a combination of Qi deficiency, blood stasis, and external evil invasion.
is a traditional Chinese medicine that ...counteracts blood stasis and has additional demonstrated effects in boosting energy and restraining inflammation.
has been employed in many traditional Chinese prescriptions that have proven effective in healing clinical dairy cow endometritis.
the
effect of
in treating endometritis was evaluated in dairy cows. In addition, bovine endometrial epithelium cell inflammation and rat blood stasis models were employed to demonstrate the crosstalk between energy, blood circulation and inflammation. Network analysis, western blotting, qRT-PCR and ELISA were performed to investigate the molecular mechanism of
in endometritis treatment.
The results demonstrate that treatment with
relieves uterine inflammation, increases blood ATP concentrations, and prolongs blood clotting times. Four of the six
main components (SMMCs) (tanshinone IIA, cryptotanshinone, salvianolic acid A and salvianolic acid B) were effective in reversing decreased ATP and increased IL-1β, IL-6, and IL-8 levels in an
endometritis model, indicating their abilities to ameliorate the negative energy balance and external evil invasion effects of endometritis. Furthermore, in a blood stasis rat model, inflammatory responses were induced in the absence of external infection; and all six SMMCs inhibited thrombin-induced platelet aggregation. Network analysis of SMMC targets predicted that
may mediate anti-inflammation via the Toll-like receptor signaling pathway; anti-aggregation via the Platelet activation pathway; and energy balance via the Thermogenesis and AMPK signaling pathways. Multiple molecular targets within these pathways were verified to be inhibited by SMMCs, including P38/ERK-AP1, a key molecular signal that may mediate the crosstalk between inflammation, energy deficiency and blood stasis.
These results provide mechanistic understanding of the therapeutic effect of
for endometritis achieved through Qi deficiency, blood stasis, and external evil invasion.
Understanding how concentrations of elements and their stoichiometry change with plant growth and age is critical for predicting plant community responses to environmental change. We used long-term ...field experiments to explore how the leaf, stem and root carbon (C), nitrogen (N) and phosphorous (P) concentrations and their stoichiometry changed with growth and stand age in a L. principis-rupprechtii Mayr. plantation from 2012-2015 in the Qinling Mountains, China. Our results showed that the C, N and P concentrations and stoichiometric ratios in different tissues of larch stands were affected by stand age, organ type and sampling month and displayed multiple correlations with increased stand age in different growing seasons. Generally, leaf C and N concentrations were greatest in the fast-growing season, but leaf P concentrations were greatest in the early growing season. However, no clear seasonal tendencies in the stem and root C, N and P concentrations were observed with growth. In contrast to N and P, few differences were found in organ-specific C concentrations. Leaf N:P was greatest in the fast-growing season, while C:N and C:P were greatest in the late-growing season. No clear variations were observed in stem and root C:N, C:P and N:P throughout the entire growing season, but leaf N:P was less than 14, suggesting that the growth of larch stands was limited by N in our study region. Compared to global plant element concentrations and stoichiometry, the leaves of larch stands had higher C, P, C:N and C:P but lower N and N:P, and the roots had greater P and C:N but lower N, C:P and N:P. Our study provides baseline information for describing the changes in nutritional elements with plant growth, which will facilitates plantation forest management and restoration, and makes a valuable contribution to the global data pool on leaf nutrition and stoichiometry.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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