Notes

Difficulties on the Au/ZrS3(001) interface probed simply by x-ray photoemission spectroscopy.
Combined with the literature analyses, the results also suggested that the cell membrane is the main site of flavonoids acting on gram-positive bacteria, and which likely involves the damage of phospholipid bilayers, the inhibition of the respiratory chain or the ATP synthesis, or some others.MicroRNAs have emerged as key regulators in vascular diseases and are involved in the formation of atherosclerotic lesions. However, the atherosclerotic-specific MicroRNAs and their functional roles in atherosclerosis are unclear. Here, we report that miR-378c protects against atherosclerosis by directly targeting Sterile Alpha Motif Domain Containing 1 (Samd1), a predicted transcriptional repressor. miR-378c was strikingly reduced in atherosclerotic plaques and blood of acute coronary syndrome (ACS) patients relative to healthy controls. Suppression of miR-378c promoted vascular smooth muscle cells (VSMCs) phenotypic transition during atherosclerosis. We also reported for the first time that Samd1 prolonged immobilization of LDL on the VSMCs, thus facilitated LDL oxidation and subsequently foam cell formation. Further, we found that Samd1 contains predicted DNA binding domain and directly binds to DNA regions as a transcriptional repressor. Together, we uncovered a novel mechanism whereby miR-378c-Samd1 circuit participates in two key elements of atherosclerosis, VSMCs phenotypic transition and LDL oxidation. Our results provided a better understanding of atherosclerosis pathophysiology and potential therapeutic management by targeting miR-378c-Samd1 circuit.We assessed the prevalence and factors related to the time to antiretroviral (ART) initiation among persons who entered HIV care and subsequently started ART in Croatia from 2005 to 2014. Included were patients ≥ 18 years, the follow-up ended on Dec/31/2017. 628 patients were included into the study 91.9% were men; median age was 36.1 (Q1-Q3 29.6-43.8) years. Rapid (within 7 days of diagnosis) ART initiation was observed in 21.8% patients, 49.8% initiated ART within 30 days, 21.7% and 28.5% had intermediate (31 days-1 year) and late initiation (> 1 year), respectively. Of 608 patients that achieved an undetectable viral load, 94% had a plasma HIV-1 RNA  less then  50 copies/ml at last measurement after a median follow-up of 5.2 years. On quantile regression analysis, calendar year of entry into care, and markers of more advanced HIV disease (higher viral load, lower CD4 cell count and clinical AIDS) were significantly associated with earlier ART initiation. Early ART was not related to a gap in care afterwards at all quantiles. In conclusion, a significant proportion of patients started ART early in Croatia in 2005-2014. Early ART initiation led to durable viral load suppression and was not associated with a subsequent gap in care.
This study aimed to evaluate the efficacy and safety of anlotinib as a third-line and subsequent treatment for patients with small cell lung cancer (SCLC).

We conducted this Phase 2 trial at 11 institutions in China. Patients with pathologically confirmed SCLC who failed at least two lines of chemotherapy were enrolled. Subjects were randomly assigned in a 21 ratio to receive either anlotinib 12 mg orally once daily for 14 days every 3 weeks or placebo. The primary endpoint was progression-free survival (PFS).

Between March 30, 2017 and June 8, 2018, a total of 82 and 38 patients were randomly assigned to receive anlotinib and placebo. The median PFS was significantly longer in the anlotinib group compared with the placebo group (4.1 months [95% confidence interval (CI), 2.8-4.2] vs 0.7 months [95% CI, 0.7-0.8]; hazard ratio (HR) 0.19 [95% CI, 0.12-0.32], p < 0.0001). Overall survival (OS) was significantly longer with anlotinib than placebo (7.3 months [95% CI, 6.1-10.3] vs 4.9 months [95% CI, 2.7-6.0]; HR 0.53 [95% CI, 0.34-0.81], p = 0.0029).

Anlotinib as a third-line or subsequent treatment for Chinese patients with SCLC showed improved PFS and OS than placebo with favourable safety profile.

ClinicalTrials.gov, number NCT03059797.
ClinicalTrials.gov, number NCT03059797.
We conducted a systematic review and meta-analysis of prospective studies to clarify the relation of fruit and vegetable consumption with incident breast cancer.

We searched systematically PubMed and EMBASE databases up to November 2020 to include prospective studies that reported the association of fruit and vegetable consumption with incidentbreast cancer. The pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated for the highest versus the lowest category of total fruit and vegetable,total fruitand total vegetable consumption, as well as fruit juice and subgroups of vegetables in relation to breast cancer incidence, using a random-effect model.

Total fruit and vegetable consumption was associated with lower overall (RR = 0.91, 95% CI = 0.87-0.95) and postmenopausal breast cancer risk (RR = 0.88, 95% CI = 0.79-0.99). Total fruit consumption was associated with lower overall (RR = 0.93, 95% CI = 0.88-0.99) and postmenopausal breast cancer risk (RR = 0.93, 95% CI = 0.87-0.99). Total fruit and vegetable intake were associated with 11% and 26% lower risk of oestrogen- and progesterone-receptor-positive (ER+/PR+) and -negative (ER-/PR-) breast cancer, respectively. Total vegetable consumption was associated with 27% lower risk of ER-/PR- breast cancer. Fruit juice consumption was associated with increased overall breast cancer risk (RR = 1.04, 95% CI = 1.01-1.07). We did not find significant associations for subgroups of vegetable intake and breast cancer risk.

These findings suggest that high total fruit and vegetable consumption are associated with reduced risk of overall, postmenopausal, ER+/PR+and ER-/PR- breast cancer.
These findings suggest that high total fruit and vegetable consumption are associated with reduced risk of overall, postmenopausal, ER+/PR+ and ER-/PR- breast cancer.
Lower-grade gliomas (LGGs) show highly metabolic heterogeneity and adaptability. To develop effective therapeutic strategies targeting metabolic processes, it is necessary to identify metabolic differences and define metabolic subtypes. Here, we aimed to develop a classification system based on metabolic gene expression profile in LGGs.

The metabolic gene profile of 402 diffuse LGGs from the Cancer Genome Atlas (TCGA) was used for consensus clustering to determine robust clusters of patients, and the reproducibility of the classification system was evaluated in three Chinese Glioma Genome Atlas (CGGA) cohorts. Then, the metadata set for clinical characteristics, immune infiltration, metabolic signatures and somatic alterations was integrated to characterise the features of each subtype.

We successfully identified and validated three highly distinct metabolic subtypes in LGGs. M2 subtype with upregulated carbohydrate, nucleotide and vitamin metabolism correlated with worse prognosis, whereas M1 subtype with upregulated lipid metabolism and immune infiltration showed better outcome. M3 subtype was associated with low metabolic activities and displayed good prognosis. Three metabolic subtypes correlated with diverse somatic alterations. Finally, we developed and validated a metabolic signature with better performance of prognosis prediction.

Our study provides a new classification based on metabolic gene profile and highlights the metabolic heterogeneity within LGGs.
Our study provides a new classification based on metabolic gene profile and highlights the metabolic heterogeneity within LGGs.
In the Women's Health Initiative (WHI) dietary modification (DM) randomised trial, the low-fat dietary intervention reduced deaths from breast cancer (P = 0.02). Extending these findings, secondary analysis examined dietary intervention influence on breast cancer mortality by metabolic syndrome (MS) components.

In total, 48,835 postmenopausal women with no prior breast cancer were randomised to a low-fat dietary intervention or comparison groups. Four MS components were determined at entry in 45,833 participants (1) high waist circumference, (2) high blood pressure, (3) high cholesterol and (4) diabetes history. Forest plots of hazard ratios (HRs) were generated with P-values for interaction between randomisation groups and MS component score. Primary outcome was death from breast cancer by metabolic syndrome score.

HRs and 95% confidence intervals (CI) for dietary intervention influence on death from breast cancer were with no MS components (n = 10,639), HR 1.09, 95% CI 0.63-1.87; with 1-2 MS components (n = 30,948), HR 0.80, 95% CI 0.62-1.02; with 3-4 MS components (n = 4,246), HR 0.31, 95% CI 0.14-0.69 (interaction P = 0.01).

While postmenopausal women with 3-4 MS components were at higher risk of death from breast cancer, those randomised to a low-fat dietary intervention more likely had reduction in this risk.

ClinicalTrials.gov (NCT00000611).
ClinicalTrials.gov (NCT00000611).
The objective of this study was to establish the contribution of PALB2 mutations to prostate cancer risk and to estimate survival among PALB2 carriers.

We genotyped 5472 unselected men with prostate cancer and 8016 controls for two Polish founder variants of PALB2 (c.509_510delGA and c.172_175delTTGT). In patients with prostate cancer, the survival of carriers of a PALB2 mutation was compared to that of non-carriers.

A PALB2 mutation was found in 0.29% of cases and 0.21% of controls (odds ratio (OR) = 1.38; 95% confidence interval (CI) 0.70-2.73; p = 0.45). PALB2 mutation carriers were more commonly diagnosed with aggressive cancers of high (8-10) Gleason score than non-carriers (64.3 vs 18.1%, p < 0.0001). The OR for high-grade prostate cancer was 8.05 (95% CI 3.57-18.15, p < 0.0001). After a median follow-up of 102 months, the age-adjusted hazard ratio for all-cause mortality associated with a PALB2 mutation was 2.52 (95% CI 1.40-4.54; p = 0.0023). The actuarial 5-year survival was 42% for PALB2 carriers and was 72% for non-carriers (p = 0.006).

In Poland, PALB2 mutations predispose to an aggressive and lethal form of prostate cancer.
In Poland, PALB2 mutations predispose to an aggressive and lethal form of prostate cancer.NAFLD is a leading comorbidity in HIV with an exaggerated course compared to the general population. Tesamorelin has been demonstrated to reduce liver fat and prevent fibrosis progression in HIV-associated NAFLD. We further showed that tesamorelin downregulated hepatic gene sets involved in inflammation, tissue repair, and cell division. Nonetheless, effects of tesamorelin on individual plasma proteins pertaining to these pathways are not known. Leveraging our prior randomized-controlled trial and transcriptomic approach, we performed a focused assessment of 9 plasma proteins corresponding to top leading edge genes within differentially modulated gene sets. ABT-199 Tesamorelin led to significant reductions in vascular endothelial growth factor A (VEGFA, log2-fold change - 0.20 ± 0.35 vs. 0.05 ± 0.34, P = 0.02), transforming growth factor beta 1 (TGFB1, - 0.35 ± 0.56 vs. - 0.05 ± 0.43, P = 0.05), and macrophage colony stimulating factor 1 (CSF1, - 0.17 ± 0.21 vs. 0.02 ± 0.20, P = 0.004) versus placebo. Among tesamorelin-treated participants, reductions in plasma VEGFA (r = 0.
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