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Electrospray Ionization Mass Spectrometry (ESI‐MS) technique and density functional theory (DFT) calculations were combined to study the formation of the complexes of lanthanides (Ln = La, Ce, Nd, Sm, Eu, Yb) and actinides (UO22+, Th4+) with CyMe4‐BTBP (6,6′‐bis(5,5,8,8‐tetramethyl‐5,6,7,8‐tetrahydro‐benzo‐[1,2,4‐]triazin‐3‐yl)‐[2,2′]bipyridine) to understand the mechanisms during the extraction process. Mass spectrometry titrations showed the formation of the complexation in acetonitrile. For lanthanides, only 1:2 complexes ([Ln(L)2]3+, [Ln(L)2(CH3CN)]3+), [Ln(L)2(NO3)]2+) were found at low [Ln]/[L] concentration ratios, whereas the 1:1 complexes ([Ln(L)(NO3)2]+) were observed when the [Ln]/[L] concentration ratio reached 1.0. For uranyl complexes, 1:1 complex ([UO2L(NO3)]+) was the only species within the measuring range. Th4+ complexes had two compositions: 1:1 and 1:2, in which 1:2 species was the dominant complex. Collision‐induced dissociation (CID) was employed to characterize the fragmentation process. The fragmentation process was unfolded sequentially on both sides of CyMe4‐BTBP ligand with the loss of alkyl groups and cleavage of triazinyl rings. The CID results of CyMe4‐BTBP complexes revealed a slight difference depending on the metal center. The DFT calculations showed that the stable complexes formed in acetonitrile solution were consistent with the ESI‐MS results. [ABSTRACT FROM AUTHOR]

BACKGROUND Mitochondrial DNA (mtDNA) pathogenic variants have been identified to be associated with maternally inherited essential hypertension (MIEH). However, the distinctive clinical features and molecular pathogenesis of MIEH are not fully understood. METHODS In this study, we collected a Chinese MIEH family with extraordinary higher penetrance of essential hypertension (88.89%) and early ages of onset (31–40 years old), and performed clinical and genetic characterization for this family. The complete mitochondrial genome of the proband was sequenced and analyzed. RESULTS The maternally related members in this family were presented with severe increased blood pressure, left ventricular remodeling, and metabolic abnormalities. Through sequencing the entire mtDNA of the proband and performing systematic analysis of the mtDNA variants with a phylogenic approach, we identified a potentially pathogenic tRNA variant (m.15992A>G in the MT-TP gene) that may account for the MIEH in this family. One nonsynonymous variant (m.15077G>A in the MT-CYB gene) was identified to play a synergistic role with m.15992A>G to cause a high penetrance of MIEH. CONCLUSIONS Our results, together with previous findings, have indicated that tRNA pathogenic variants in the mtDNA could act important roles in the pathogenesis of MIEH through reducing mitochondrial translation and disturbing mitochondrial function. [ABSTRACT FROM AUTHOR]

Objective · To analyze the influencing factors of frailty syndrome in elderly patients with stable coronary artery disease (SCAD). Methods · A total of 101 SCAD patients (aged ≥ 60 years) hospitalized in the Department of Geriatrics and Cardiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine from March to September, 2019, were selected. The comprehensive geriatric assessment was used to evaluate the health status and complications of the patients. According to patients' frailty status evaluated by the Fried frailty phenotype, the patients were divided into frailty group and non-frailty group. Multivariate Logistic regression model was used to analyze the influencing factors of frailty syndrome in elderly patients with SCAD. Results · Among 101 elderly patients with coronary heart disease, 53 cases were complicated with frailty syndrome. There were statistically significant differences in age, Charlson comorbidity index (CCI), the proportion of sleep disorders, falls in the past year, history of multiple drug use, grip strength, Gensini score, cystatin level, brain natriuretic peptide (BNP) and serum creatinine (Scr) levels between the two groups (all P<0.05). Multivariate Logistic regression analysis showed that Gensini score (β=0.027, SE=0.012, P=0.028) and grip strength (β=-0.076, SE=0.030, P=0.012) were the influencing factors of elderly SCAD patients complicated with frailty syndrome. Conclusion · Elderly patients with SCAD are prone to be complicated with frailty syndrome. The Gensini score and grip strength measurement will help clinicians identify and intervene in frailty syndrome early. [ABSTRACT FROM AUTHOR]

Drugs targeting the vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling (anti-VEGF/VEGFR drugs) are the most validated anti-angiogenic strategies for cancer treatment. Complete response (CR) is a rare event in cancer patients receiving chemotherapy. A meta-analysis was conducted to determine whether adding anti-VEGF/VEGFR drugs to chemotherapy can further increase the chance of CR in the first-line therapy. Relevant databases were systematically searched for the period 2000-2015. Eligible studies were selected according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The incidence, relative risk (RR), and 95 % confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies. A total of 12,453 patients from 28 randomized controlled trials were included. The overall incidence of CR in patients treated with anti-VEGF/VEGFR drugs plus chemotherapy was 1.5 % (95 % CI, 1.0-2.0 %) compared to 1.1 % (95 % CI, 0.7-1.4 %) in the chemotherapy-alone arm. Adding anti-VEGF/VEGFR drugs was associated with significant improvement of CR (RR, 1.52, 95 % CI, 1.18-1.95, P = 0.001). When stratified by drug type, adding VEGFR tyrosin kinase inhibitors (TKIs) did not increase the chance of CR (RR, 0.87, 95 % CI, 0.51-1.49; P = 0.614). The addition of bevacizumab with 7.5 mg/kg every 3 weeks, but not 15 mg/kg every 3 weeks, significantly improves the CR (7.5 mg, RR, 2.43, 95 % CI, 1.64-3.60, P = 0.000; 15 mg, RR, 1.07, 95 % CI, 0.63-1.81, P = 0.799). In subgroup analysis, a significant improvement of CR by the addition of anti-VEGF/VEGFR drugs was observed in patients with colorectal cancer (RR, 2.10, 95 % CI 1.21-3.63, P = 0.008), ovarian cancer (RR, 3.07; 95 % CI, 1.68-5.62, P = 0.000), and patients who are treated with platinum-based regimens (RR, 1.78, 95 % CI, 1.23-2.59, P = 0.002). Low-dose bevacizumab, rather than VEGFR TKIs or high-dose bevacizumab, can increase the chance of CR in patients receiving chemotherapy. [ABSTRACT FROM AUTHOR]

Electrospray Ionization Mass Spectrometry (ESI-MS) technique and density functional theory (DFT) calculations were combined to study the formation of the complexes of lanthanides (Ln = La, Ce, Nd, Sm, Eu, Yb) and actinides (UO 2 2+ , Th 4+ ) with CyMe 4 -BTBP (6,6'-bis(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-benzo-[1,2,4-]triazin-3-yl)-[2,2']bipyridine) to understand the mechanisms during the extraction process. Mass spectrometry titrations showed the formation of the complexation in acetonitrile. For lanthanides, only 1:2 complexes ([Ln(L) 2 ] 3+ , [Ln(L) 2 (CH 3 CN)] 3+ ), [Ln(L) 2 (NO 3 )] 2+ ) were found at low [Ln]/[L] concentration ratios, whereas the 1:1 complexes ([Ln(L)(NO 3 ) 2 ] + ) were observed when the [Ln]/[L] concentration ratio reached 1.0. For uranyl complexes, 1:1 complex ([UO 2 L(NO 3 )] + ) was the only species within the measuring range. Th 4+ complexes had two compositions: 1:1 and 1:2, in which 1:2 species was the dominant complex. Collision-induced dissociation (CID) was employed to characterize the fragmentation process. The fragmentation process was unfolded sequentially on both sides of CyMe 4 -BTBP ligand with the loss of alkyl groups and cleavage of triazinyl rings. The CID results of CyMe 4 -BTBP complexes revealed a slight difference depending on the metal center. The DFT calculations showed that the stable complexes formed in acetonitrile solution were consistent with the ESI-MS results., (© 2023 John Wiley & Sons Ltd.)

Low-dose ionizing radiation (LDIR) induces hormesis, exerts an adoptive effect on normal mammalian cells and stimulates cell proliferation; however, this effect is absent in cancer cells. Little is known on the molecular mechanisms underlying this differential response between normal and cancer cells. In the present study, it was demonstrated that the human prostate cancer cell line PC-3 and the normal prostate cell line RWPE-1 exhibited differential biological responses to LDIR. Through cell cycle analyses, it was demonstrated that LDIR inhibited cell growth and arrested the cell cycle at the S and G2/M phases in PC-3 cells, but not in RWPE-1 cells. Using western blotting, it was demonstrated that LDIR at 75 mGy induced the expression of ataxia-telangiectasia mutated (ATM) protein in PC-3 as well as RWPE-1 cells. However, the ATM̸p21 pathway was activated in PC-3, but not in RWPE-1 cells. Although the expression of p53 was not affected by 75 mGy LDIR in RWPE-1 cells, the ATM̸p21 pathway was activated when RWPE-1 cells lost p53 function. In addition, when using ATM inhibitors, the ATM̸p21 pathway was inactivated in both cell lines, and the LDIR-induced cell proliferation inhibition was also abolished. These findings suggested that the ATM/p21 pathway directly participated in the LDIR-induced cell proliferation inhibition in p53null type prostate tumor cells, whereas this mechanism was absent in normal prostate cells. Thus, p53 may affect cell stability following LDIR, and plays a crucial role in regulating the ATM/p21 pathway activated by LDIR.

Low-dose irradiation (LDIR) has been proven to have differential biological effects on normal mammalian somatic cells and cancer cells. Our previous study showed that p53 gene status is a critical factor regulating the effect of LDIR on cancer cells. We investigated the effect of LDIR on the breast cancer cell line MDA-MB-231 that harbors a mutant p53 gene, and the normal breast fibroblast cell line Hs 578Bst. In the present study, we showed that 150 mGy LDIR pormoted growth of MDA-MB-231 cells but not Hs 578Bst cells. Through cell cycle analyses, we found that LDIR accelerated cell cycle into S phase in MDA-MB-231 cells, but did not affect the cell cycle of Hs 578Bst cells. Using western blotting, we demonstrated that the expression of CDK4, CDK6 and cyclin D1 was upregulated in MDA-MB-231 cells after LDIR. Although LDIR increased ataxia-telangiectasia mutated (ATM) level in both MDA-MB-231 cells and Hs 578Bst cells and activated ATM/p53/p21 pathway, only the mutant type of p53 (mtp53) protein in MDA-MB-231 cells was shown to be accumulated after LDIR. Using ATM inhibitor or lentivirus-mediated small interfering RNA (siRNA) to block the ATM/p53/p21 pathway in MDA-MB-231 cells, the LDIR-induced cell proliferation was abolished. When we introduced wild-type p53 (wtp53) protein into MDA-MB-231 cells, the LDIR-induced cell proliferation was also abolished. These findings suggest that normal p53 function is crucial in ATM/p53/p21 pathway activated by LDIR. The p53 status is the most probable reason leading to differential LDIR biological activities between breast tumor cells and normal breast cells.

Drugs targeting the vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling (anti-VEGF/VEGFR drugs) are the most validated anti-angiogenic strategies for cancer treatment. Complete response (CR) is a rare event in cancer patients receiving chemotherapy. A meta-analysis was conducted to determine whether adding anti-VEGF/VEGFR drugs to chemotherapy can further increase the chance of CR in the first-line therapy. Relevant databases were systematically searched for the period 2000-2015. Eligible studies were selected according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The incidence, relative risk (RR), and 95 % confidence intervals (CIs) were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies. A total of 12,453 patients from 28 randomized controlled trials were included. The overall incidence of CR in patients treated with anti-VEGF/VEGFR drugs plus chemotherapy was 1.5 % (95 % CI, 1.0-2.0 %) compared to 1.1 % (95 % CI, 0.7-1.4 %) in the chemotherapy-alone arm. Adding anti-VEGF/VEGFR drugs was associated with significant improvement of CR (RR, 1.52, 95 % CI, 1.18-1.95, P = 0.001). When stratified by drug type, adding VEGFR tyrosin kinase inhibitors (TKIs) did not increase the chance of CR (RR, 0.87, 95 % CI, 0.51-1.49; P = 0.614). The addition of bevacizumab with 7.5 mg/kg every 3 weeks, but not 15 mg/kg every 3 weeks, significantly improves the CR (7.5 mg, RR, 2.43, 95 % CI, 1.64-3.60, P = 0.000; 15 mg, RR, 1.07, 95 % CI, 0.63-1.81, P = 0.799). In subgroup analysis, a significant improvement of CR by the addition of anti-VEGF/VEGFR drugs was observed in patients with colorectal cancer (RR, 2.10, 95 % CI 1.21-3.63, P = 0.008), ovarian cancer (RR, 3.07; 95 % CI, 1.68-5.62, P = 0.000), and patients who are treated with platinum-based regimens (RR, 1.78, 95 % CI, 1.23-2.59, P = 0.002). Low-dose bevacizumab, rather than VEGFR TKIs or high-dose bevacizumab, can increase the chance of CR in patients receiving chemotherapy.

Objective: To investigate the distribution characteristics of mineral elements in the soil of Angelica sinensis producing regions and its relationship with altitude and soil types., Methods: The contents of 15 mineral elements in 103 batches of soil from 13 counties were determined by ICP-MS or AAS. Pearson correlation analysis, partial correlation analysis and systematical cluster analysis were used to analyze the data., Results: Pearson correlation analysis showed that the content of Mg in soil and altitude showed significant positive correlation(P <0. 01), the content of Cd in soil and altitude showed significant negative correlation(P <0. 05), and the con- tents of Pb, Cd, As, Cu, Cr as well as Ni in soil and altitude showed negative correlation. The result of systematic cluster analysis showed that 103 batches of soil were clustered into 5 groups. The main soil types of group I were black soil, haplic kastanozems and black sandy-soil, group II was loess, group III was cinnamon soil, group IV were red soil and grey cinnamon soil, and group V were black soil, haplic kastanozems, grey cinnamon soil and cinnamon soil., Conclusion: The distribution of mineral elements in soil is closely related to altitude and soil types.