Aluminum (Al) is delivered to surface ocean waters by aeolian dust, making it a promising tracer to constrain dust deposition rates and the atmospheric supply of trace metal micronutrients. Over ...recent years, dissolved Al has been mapped along the GEOTRACES transects, providing unparalleled coverage of the world ocean. However, inferring atmospheric input rates from these observations is complicated by a suite of additional processes that influence the Al distribution, including reversible particle scavenging, biological uptake by diatoms, hydrothermal sources, sediment resuspension. Here we employ a data‐assimilation model of the oceanic Al cycle that explicitly accounts for these processes, allowing the atmospheric signal to be extracted. We conduct an ensemble of model optimizations that test different dust deposition distributions and consider spatial variations in Al solubility, thereby inferring the atmospheric Al supply that is most consistent with GEOTRACES observations. We find that 37.2 ± 11.0 Gmol/yr of soluble Al is added to the global ocean, dominated in the Atlantic Ocean, and that Al fractional solubility varies strongly as a function of atmospheric dust concentration. Our model also suggests that 6.1 ± 2.4 Gmol Al/yr is injected from hydrothermal vents, and that vertical Al redistribution through the water column is dominated by abiotic reversible scavenging rather than uptake by diatoms. Our results have important implications for the oceanic iron (Fe) budget: based on the soluble Fe:Al ratio of dust, we infer that aeolian Fe inputs lie between 3.82 and 9.25 Gmol/yr globally, and fall short of the biological Fe demand in most ocean regions.
Key Points
We employ an Al cycle model that considers 12 dust deposition patterns and assimilates GEOTRACES data to constrain soluble Al deposition
We find ∼37 ± 11.0 Gmol Al/yr is added to the surface ocean by dust, and dust solubility varies spatially with atmospheric dust loading
Fe inputs from dust likely fall short of the biological demand in most regions, highlighting the importance of other Fe supply mechanisms
While IL-2 can potently activate both NK and T cells, its short in vivo half-life, severe toxicity, and propensity to amplify Treg cells are major barriers that prevent IL-2 from being widely used ...for cancer therapy. In this study, we construct a recombinant IL-2 immunocytokine comprising a tumor-targeting antibody (Ab) and a super mutant IL-2 (sumIL-2) with decreased CD25 binding and increased CD122 binding. The Ab-sumIL2 significantly enhances antitumor activity through tumor targeting and specific binding to cytotoxic T lymphocytes (CTLs). We also observe that pre-existing CTLs within the tumor are sufficient and essential for sumIL-2 therapy. This next-generation IL-2 can also overcome targeted therapy-associated resistance. In addition, preoperative sumIL-2 treatment extends survival much longer than standard adjuvant therapy. Finally, Ab-sumIL2 overcomes resistance to immune checkpoint blockade through concurrent immunotherapies. Therefore, this next-generation IL-2 reduces toxicity while increasing TILs that potentiate combined cancer therapies.
•The comparative effects of different teas, prepared from the same fresh leaves, were studied.•The relationship among various teas and their effect on bile acid metabolism was investigated.•Green, ...black, oolong, and white teas altered the bile acid metabolism.•Changes in bile acid metabolism could be associated with the health benefit effects of tea.•Oolong tea was found to be the most effective in reducing weight.
The beneficial effects of tea on health, including obesity, are well known. However, the comparative effects of black, green, white, and oolong teas, which are prepared from the same fresh leaves, on weight gain and the potential mechanisms involved are not yet fully understood. Bile acids (BAs) are shown to be powerful regulators of metabolism; however, to our knowledge, no studies have investigated the effect of tea on BA metabolism. The aim of this study was to investigate the modulatory effects that green, black, white, and oolong teas that were prepared from the same raw tea leaves have on the plasma BA profile.
Female rats were dosed with the aforementioned tea types as their sole source of drinking fluid for 28 d. We then investigated their weight and effect on BA metabolic profile using advanced ultra-performance liquid chromatography–tandem mass spectrometer (UPLC-MS/MS)-based metabolomics.
The UPLC-MS/MS analysis of the plasma show that the levels of murocholic acid, glycochenodeoxycholic acid, glycocholic acid, glycodeoxycholic acid, taurochenodeoxycholic acid, tauroursodeoxycholic acid, taurodeoxycholic acid, tauromuricholic acid, and taurocholic acid were increased; whereas levels of taurolithocholic acid and isolithocholic acid were decreased after drinking green, oolong, and white tea types compared with control. Surprisingly, oolong tea significantly influenced reduction in relative weight compared with control, black, and green tea; whereas black, green, and white teas had no effects on weight compared with control.
Green, black, oolong, and white teas altered the BA metabolism. This change in BA metabolism could be associated with the health benefit effects of tea. Oolong tea was most effective in reducing weight.
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•Metformin use was associated with a decreased risk of HCC in DM.•Metformin use was associated with a decreased all-cause mortality of HCC in DM.•More prospective studies are needed to verify the ...accuracy of the findings.
The views regarding the associations between metformin use and hepatocellular carcinoma (HCC) among diabetes mellitus (DM) patients are divisive. Thus we summarized all available published studies evaluating the relationship between metformin therapy and HCC survival and risk, and aim to conduct an updated meta-analysis study to more accurately clarify the association.
We searched for articles regarding impact of metformin use on risk and mortality of HCC in DM and published before April 2021 in databases (PubMed and Web of Science). We used STATA 12.0 software to compute odds ratios (ORs)/relative risks (RRs) or hazard ratios (HRs) and their 95% confidence intervals (CIs) to generate a computed effect size and 95% CI.
The present study showed that metformin use was associated with a decreased risk of HCC in DM with a random effects model (OR/RR = 0.59, 95% CI 0.51–0.68, I2 = 96.5%, p < 0.001). In addition, the study indicated that metformin use was associated with a decreased all-cause mortality of HCC in DM with a random effects model (HR = 0.74, 95% CI 0.66–0.83, I2 = 49.6%, p = 0.037).
In conclusion, our studies support that the use of metformin in DM patients is significantly associated with reduced risk and all-cause mortality of HCC. And more prospective studies focusing on the metformin therapy as a protective factor for HCC are needed to verify the accuracy of the findings.
► A standardised HPLC–UV–MS method for tea analyses has been established. ► Pertinent phenolic compounds in Chinese teas have been identified and quantified. ► Total catechin content might help to ...classify tea according to the future application.
A standardised profiling method based on high performance liquid chromatography combined with ultraviolet (UV) and mass spectrometric detection (MS) was established to analyse the phenolic compounds of selected tea varieties used for manufacturing of green, black and oolong teas. The composition and content of 24 tea constituents were analysed, including catechins, flavonol and flavones glycosides, phenolic acids and purine alkaloids. Each tea variety had a unique chemical profile. The compositions of catechins were lower in the tea varieties for green tea manufacturing, while the content of myricetin glycosides was the lowest in the tea variety for oolong tea manufacturing. The content of individual phenolic compounds in the selected tea varieties is highly variable. However, the content of total catechins is proposed to be helpful to classify tea according to the future application as non fermented green and fermented oolong or black tea.
•Aromatic profiles of 75 samples of 5 varieties were analysed by HS-SPME/GC–MS.•A model was developed to simultaneously discriminate the 5 oolong varieties.•Twenty-six major volatiles (22 identified) ...were determined for oolong tea.•Variety is a dominant feature for aromatic profiles of oolong tea.
This study aimed to develop an objective and accurate analytical method to discriminate oolong tea varieties that easily causing adulteration by potential volatile compounds. A total of 75 oolong tea samples of five similar varieties (Tieguanyin, Benshan, Maoxie, Huangjingui and Jinguanyin) were analysed by headspace solid phase microextraction (HS-SPME) coupled with gas chromatography–mass spectrometry (GC–MS). The relative content of 26 major volatile compounds varied significantly according to variety, combined with the results of hierarchical cluster analysis (HCA), indicating that the varietal differences of aromatic profile remain significant for tea cultivars with very close origin. Principal component analysis (PCA) of the aromatic profiles showed that the feature of variety dominated over the other features (like producing region and quality). By stepwise linear discriminant analysis (S-LDA), 18 volatiles with the best discriminating capacity were selected, and 4 discriminant functions (DFs) enabled simultaneously discrimination of the five oolong varieties with 100% correct rate.
Background
Concerns for hyperkalaemia limit the use of mineralocorticoid receptor antagonists (MRAs). The frequency of MRA‐associated hyperkalaemia in real‐world settings and the extent of subsequent ...MRA discontinuation are poorly quantified.
Methods and results
Observational study including all Stockholm citizens initiating MRA therapy during 2007–2010. Hyperkalaemias were identified from all potassium (K+) measurements in healthcare. MRA treatment lengths and dosages were obtained from complete collection of pharmacy dispensations. We assessed the 1‐year incidence and clinical hyperkalaemia predictors, and quantified drug prescription changes after an episode of hyperkalaemia. Overall, 13 726 new users of MRA were included, with median age of 73 years, 53% women and median plasma K+ of 3.9 mmol/L. Within a year, 18.5% experienced at least one detected hyperkalaemia (K+ > 5.0 mmol/L), the majority within the first 3 months of therapy. As a comparison, hyperkalaemia was detected in 6.4% of propensity‐matched new beta‐blocker users. Chronic kidney disease (CKD), older age, male sex, heart failure, peripheral vascular disease, diabetes and concomitant use of angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, beta‐blockers and diuretics were associated with increased hyperkalaemia risk. After hyperkalaemia, 47% discontinued MRA and only 10% reduced the prescribed dose. Discontinuation rates were higher after moderate/severe (K+ > 5.5 mmol/L) and early in therapy (<3 months from initiation) hyperkalaemias. CKD participants carried the highest risk of MRA discontinuation in adjusted analyses. When MRA was discontinued, most patients (76%) were not reintroduced to therapy during the subsequent year.
Conclusion
Among real‐world adults initiating MRA therapy, hyperkalaemia was very common and frequently followed by therapy interruption, especially among participants with CKD.
Correction of leg length discrepancy (LLD) in skeletally mature patients with osteosarcoma was rarely reported and quite challenging. This study aimed to propose a treatment strategy of staged ...lengthening and reconstruction with a standard static prosthesis to address LLD and restore limb function. It also evaluated the effectiveness of the strategy in terms of leg lengthening, functional outcomes, and complications. The strategy for lengthening included three stages. In stage 1, the previous prosthesis was removed and an external fixator with a temporary rod-cement spacer was placed. In this stage, the external fixator was used to lengthen the limb to the appropriate length. In stage 2, the external fixator was removed and the old rod-cement spacer was replaced with a new one. In stage 3, the rod-cement spacer was removed and the standard static prosthesis was planted. Nine skeletally mature distal femoral osteosarcoma patients with unacceptable LLD were treated in our institution from 2019 to 2021. We performed a chart review on nine patients for the clinical and radiographic assessment of functional outcomes, LLD, and complications. The mean (range) leg lengthening was 7.3 cm (3.6-15.6). The mean (range) LLD of the lower limbs decreased from 7.6 cm (4.1-14.2) before the lengthening to 0.3 cm (- 0.3 to 2.1) at the final follow-up with statistical significance (P = 0.000). The mean (range) Musculoskeletal Tumor Society score improved from 30.3% (16.7%-53.3%) before the lengthening to 96.3% (86.7%-100%) at the final follow-up with statistical significance (P = 0.000). Three patients (33.3%) had a minor complication; none needed additional surgical intervention. In the short term, the current staged lengthening and reconstruction with standard static prosthesis provided satisfactory functional outcomes and LLD correction with few complications. The long-term effects of this method need further exploration.
The effect of milk on the absorption of polyphenols is still controversial so far. In order to determine the impact of milk addition on green tea catechins bioaccessibility and intestinal absorption ...an in vitro digestion/Caco-2 cell model was applied. Green tea extract (GTE) was solubilized in distilled water at 23°C and 100°C, combined with skimmed milk (GTE+10% milk and GTE+25% milk) and subjected to simulated gastric and intestinal digestion, followed by transepithelial absorption in Caco-2 cells monolayers. In the mixture with milk, gallated catechins: ECG and EGCG showed binding to milk proteins while EC and EGC seemed to have weaker affinity. Catechins were stable during gastric incubation and very sensitive to intestinal digestion. Bioaccessibility of green tea catechins brewed at 100°C was higher than brewed at 23°C. Catechins from digested GTE with 10% and 25% milk exhibited enhanced intestinal permeability in Caco-2 model in comparison to non-digested GTE and digested GTE without milk. Apparent permeability coefficients (Papp) of EGCG and ECG in digested GTE with 25% milk were significantly higher compared to those in GTE with 10% milk, and amounted to 2.41×10−6cm/s and 1.39×10−6cm/s. The recoveries of all catechins in GTE with milk in Caco-2 cells after 2h incubation were significantly higher than that without milk. To summarize, these data suggest that milk addition may increase catechin bioavailability by enhancing their transepithelial absorption and uptake from green tea extract.
► EGCG is the major catechin in the bioaccessible fraction of green tea. ► GCG is the most effectively transported catechin of green tea-milk digest. ► Milk addition increases catechins intestinal absorption from green tea.
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