'Only to reconcile with it'. The coping experience amongst middle-aged and older cancer survivors: A qualitative study.

BACKGROUND: Cancer threat is relevant to age, and the threat of a foreshortened life coupled with a lengthy treatment process negatively affects middle-aged and older adults. Understanding the coping throughout the cancer experience in middle-aged and older cancer survivors will help develop supportive care to promote their physiological and psychological coping effects. OBJECTIVES: To explore the cancer coping experiences of middle-aged adults aged 40-59 and older adults over 60. DESIGN: A descriptive phenomenological study was employed. METHODS: Face-to-face, in-depth, semistructured interviews were conducted with 22 oncology patients in a tertiary university hospital aged 40 or above from August to October 2023. The interview data were analyzed using thematic analysis procedures. RESULTS: Five themes and 13 subthemes were formed through analysis: acceptance of cancer (considering cancer as chronic, believing in fate and attributing cancer to karma); having different information needs (desired to be truthfully informed, information-seeking behaviour, information avoidance behaviour); getting families involved (developing dependent behaviours, feeling emotional support, family members suffering worse); striving to maintain positive psychological state (positive thinking, seeking peer support) and negative experience (undesirable, low self-esteem). CONCLUSION: Our study reveals that cancer survivors' attitudes towards having cancer have changed from a death sentence to a more positive perception of a chronic disease. Supportive programmes for developing coping strategies should consider the cultural traditions and religious beliefs, different information needs, involvement of family and promoting a positive psychological state while avoiding negative factors. PATIENT OR PUBLIC CONTRIBUTION: Participants with experience of coping with cancer were involved in the semistructured interview.

One-Dimensional Covalent Organic Framework as High-Performance Cathode Materials for Lithium-Ion Batteries.

Covalent organic frameworks (COFs) have emerged as a new class of cathode materials for energy storage in recent years. However, they are limited to two-dimensional (2D) or three-dimensional (3D) framework structures. Herein, this work reports designed synthesis of a redox-active one-dimensional (1D) COF and its composites with 1D carbon nanotubes (CNTs) via in situ growth. Used as cathode materials for Li-ion batteries, the 1D COF@CNT composites with unique dendritic core-shell structure can provide abundant and easily accessible redox-active sites, which contribute to improve diffusion rate of lithium ions and the corresponding specific capacity. This synergistic structural design enables excellent electrochemical performance of the cathodes, giving rise to 95% utilization of redox-active sites, high rate capability (81% capacity retention at 10 C), and long cycling stability (86% retention after 600 cycles at 5 C). As the first example to explore the application of 1D COFs in the field of energy storage, this study demonstrates the great potential of this novel type of linear crystalline porous polymers in battery technologies.

Anion-Dependent Redox Chemistry of p-Type Poly(vinyldimethylphenazine) Cathode Materials.

Metal-free organic electrode materials have attracted vast research attention owing to their designable structures and tunable electrochemical properties. Although n-type cathode materials could be used in various metal-ion batteries, p-type ones with high potential can deliver high energy density. Herein, we report a new p-type polymeric cathode material, poly(2-vinyl-5,10-dimethyl-dihydrophenazine) (PVDMP), with a theoretical capacity of 227 mAh g-1 . PVDMP featuring two-step redox reaction will be doped by two anions to maintain electroneutrality during oxidation, which resulted in an anion-dependent electrochemical behavior of PVDMP-based cathode. The suitable dopant anion for PVDMP was selected and the doping mechanism was confirmed. Under the optimized condition, PVDMP cathode can deliver a high initial capacity of 220 mAh g-1 at 5 C and even remains 150 mAh g-1 after 3900 cycles. This work not only provides a new kind of p-type organic cathode materials but also deepens the understanding of its anion-dependent redox chemistry.

Hypoadiponectinemia is associated with aortic stiffness in nondialysis diabetic patients with stage 3-5 chronic kidney disease.

OBJECTIVES: Albuminuria and serum adiponectin levels are factors that have been associated with the development of cardiovascular disease in patients with diabetes mellitus. Here we investigated the relationship between serum adiponectin levels and aortic stiffness in nondialysis diabetic kidney disease patients with stage 3-5 chronic kidney disease. METHODS: Fasting blood samples were obtained from 80 nondialysis diabetic kidney disease patients with stage 3-5 chronic kidney disease. Carotid-femoral pulse wave velocity (cfPWV) was measured using applanation tonometry; cfPWV values of >10 m/s were defined as aortic stiffness. Serum adiponectin levels were determined by enzyme immunoassay. RESULTS: Forty-two patients (52.5%) with nondialysis diabetic kidney disease were diagnosed with aortic stiffness. The patients in this group were older (p = 0.011), had higher systolic blood pressure (p = 0.002) and urine albumin-to-creatinine ratios (p = 0.013), included fewer females (p = 0.024), and had lower serum adiponectin (p = 0.001) levels than those in the control group. Multivariable logistic regression analysis revealed that serum adiponectin was independently associated with aortic stiffness (odds ratio = 0.930, 95% confidence interval: 0.884-0.978, p = 0.005) and also positively correlated with cfPWV values by multivariable linear regression (ß = -0.309, p = 0.002) in nondialysis diabetic kidney disease patients. CONCLUSIONS: The results suggested that serum adiponectin levels could be used to predict aortic stiffness in nondialysis diabetic kidney disease patients with stage 3-5 chronic kidney disease.

Novel Insight into the Potential Role of Acylglycerophosphate Acyltransferases Family Members on Triacylglycerols Synthesis in Buffalo.

Acylglycerophosphate acyltransferases (AGPATs) are the rate-limiting enzymes for the de novo pathway of triacylglycerols (TAG) synthesis. Although AGPATs have been extensively explored by evolution, expression and functional studies, little is known on functional characterization of how many members of the AGPAT family are involved in TAG synthesis and their impact on the cell proliferation and apoptosis. Here, 13 AGPAT genes in buffalo were identified, of which 12 AGPAT gene pairs were orthologous between buffalo and cattle. Comparative transcriptomic analysis and real-time quantitative reverse transcription PCR (qRT-PCR) further showed that both AGPAT1 and AGPAT6 were highly expressed in milk samples of buffalo and cattle during lactation. Knockdown of AGPAT1 or AGPAT6 significantly decreased the TAG content of buffalo mammary epithelial cells (BuMECs) and bovine mammary epithelial cells (BoMECs) by regulating lipogenic gene expression (p < 0.05). Knockdown of AGPAT1 or AGPAT6 inhibited proliferation and apoptosis of BuMECs through the expression of marker genes associated with the proliferation and apoptosis (p < 0.05). Our data confirmed that both AGPAT1 and AGPAT6 could regulate TAG synthesis and growth of mammary epithelial cells in buffalo. These findings will have important implications for understanding the role of the AGPAT gene in buffalo milk performance.

Total Synthesis of Mannopeptimycin ß via ß-Hydroxyenduracididine Ligation.

Nonribosomal peptide synthesis in bacteria has endowed cyclic peptides with fascinating structural complexity via incorporating nonproteinogenic amino acids. These bioactive cyclic peptides provide interesting structural motifs for exploring total synthesis and medicinal chemistry studies. Cyclic glycopeptide mannopeptimycins exhibit antibacterial activity against antibiotic-resistant Gram-positive pathogens and act as the lipid II binder to stop bacterial cell wall biosynthesis. Here, we report a strategy streamlining solution phase-solid phase synthesis and chemical ligation-mediated peptide cyclization for the total synthesis of mannopeptimycin ß.

Outcome of scleral buckling with or without gas tamponade for recurrent retinal detachment in post-vitrectomy eyes.

BACKGROUND: Treatment of recurrent retinal detachment (re-RD) following vitrectomy (post-gas/air tamponade and post-silicone oil removal) is challenging. Previously reported treatment is commonly revision pars plana vitrectomy (PPV) combined with tamponade, which is invasive and a burden both economically and emotionally when compared with scleral buckling (SB). The purpose of this study is to report anatomical and functional outcomes of SB with or without gas tamponade in eyes with recurrent retinal detachment (re-RD) that previously underwent PPV at least once. METHODS: We retrospectively reviewed the medical records of 14 patients (14 eyes) who underwent PPV at least once and were treated with SB after re-RD. Preoperative characteristics, intraoperative complications, and postoperative data were assessed. The final anatomical and functional outcomes were analyzed. RESULTS: The original PPV was performed for primary rhegmatogenous retinal detachment in 11 eyes, macular hole retinal detachment in 2 eyes, and myopic foveoschisis in 1 eye. Previously, 3 eyes underwent one PPV with gas tamponade, and the remaining 11 (79%) eyes underwent 2-5 operations. Seven eyes underwent the procedure with gas injection. At the last follow-up, 13 eyes achieved total retinal attachment and 1 eye had re-RD. The postoperative intraocular pressure was within the normal range, except in 1 eye (6 mmHg). The finest postoperative best-corrected visual acuity (BCVA) was 20/25. There was a significant improvement in BCVA from 20/160 ± 20/63 at baseline to 20/80 ± 20/50 at the last visit in the 13 successfully treated eyes (P = 0.025). CONCLUSIONS: SB can be effective for re-RD after PPV in specific cases.

The utility of MRI for measuring hematocrit in fetal anemia.

BACKGROUND: Doppler ultrasound measurements of the peak systolic velocity of the middle cerebral artery can be used to noninvasively diagnose fetal anemia but are less precise following fetal blood transfusion and in late gestation. We have previously demonstrated the feasibility of estimating fetal hematocrit in vitro using magnetic resonance imaging relaxation times. Here we report the use of magnetic resonance imaging as a noninvasive tool to accurately detect fetal anemia in vivo. OBJECTIVES: This study has 2 objectives: (1) to determine the feasibility and accuracy of magnetic resonance imaging in estimating hematocrit in anemic fetuses and (2) to compare magnetic resonance imaging and middle cerebral artery Doppler in detecting moderate to severe fetal anemia. STUDY DESIGN: Fetuses undergoing fetal blood sampling or transfusion underwent magnetic resonance imaging examinations prior to and following their procedures at 1.5 Tesla (Siemens Avanto). A modified Look-Locker inversion pulse sequence and T2 preparation sequence were applied for T1 and T2 mapping of the intrahepatic umbilical vein. Estimated fetal hematocrit was calculated using a combination of T1 and T2 values and compared with conventional hematocrit obtained from fetal blood samples and middle cerebral artery Doppler measurements. RESULTS: Twenty-three fetuses were assessed during 33 magnetic resonance imaging scans. The mean absolute difference between the laboratory and magnetic resonance imaging-estimated hematocrit was 0.06 ± 0.05 with a correlation of 0.77 (P < .001) determined by a multilevel, mixed-effects model adjusting for the repeated measurements from the same participants, multiple gestation pregnancies, and the scan type (ie, before or after transfusion scan). Bland-Altman analysis revealed a systematic bias of -0.03 between the magnetic resonance imaging and fetal blood sampling measurements. Magnetic resonance imaging and middle cerebral artery Doppler had similar sensitivities of approximately 90% to detect moderate to severe anemia. However, magnetic resonance imaging had a higher specificity (93% [13/14], 95% confidence interval, 66-100%) than Doppler (71% [10/14], 95% confidence interval, 42-92%). CONCLUSION: Moderate to severe fetal anemia can be detected noninvasively by magnetic resonance imaging with high sensitivity and specificity. Our results suggest an adjunct role for magnetic resonance imaging in fetuses with suspected anemia, particularly following previous transfusion and in late gestation.

Feasibility of phase-contrast cine magnetic resonance imaging for measuring blood flow in the sheep fetus.

Phase-contrast cine MRI (PC-MRI) is the gold-standard noninvasive technique for measuring vessel blood flow and has previously been applied in the human fetal circulation. We aimed to assess the feasibility of using PC-MRI to define the distribution of the fetal circulation in sheep. Fetuses were catheterized at 119-120 days of gestation (term, 150 days) and underwent MRI at ∼123 days of gestation under isoflurane anesthesia, ventilated at a FIO2 of 1.0. PC-MRI was performed using a fetal arterial blood pressure catheter signal for cardiac triggering. Blood flows were measured in the major fetal vessels, including the main pulmonary artery, ascending and descending aorta, superior vena cava, ductus arteriosus, left and right pulmonary arteries, umbilical vein, ductus venosus, and common carotid artery and were indexed to estimated fetal weight. The combined ventricular output, pulmonary blood flow, and flow across the foramen ovale were calculated from vessel flows. Intraobserver and interobserver agreement and reproducibility was assessed. Blood flow measurements were successfully obtained in 61 out of 74 vessels (82.4%) interrogated in 9 fetuses. There was good intraobserver [R = 0.998, P < 0.0001; intraclass correlation (ICC) = 0.997] and interobserver agreement (R = 0.996, P < 0.0001; ICC = 0.996). Repeated MRI measurements showed good reproducibility (R = 0.989, P = 0.0002; ICC = 0.990). We conclude that PC-MRI using fetal catheters for gating triggers is feasible in the major vessels of late gestation fetal sheep. This approach may provide a useful new tool for assessing the circulatory characteristics of fetal sheep models of human disease, including fetal growth restriction and congenital heart disease.

Cognitive Impairment and Glycemic Control in Elderly Patients Under Health-Care Case Management.

We aim to test whether the association between glucose control and cognitive function still holds true in elderly patients with diabetes mellitus (DM) and Alzheimer disease (AD) under health-care case management. We enrolled 100 patients with DM (mean age: 74.6 years; male: 49%) and 102 patients with AD (mean age: 77.9 years; male: 41.2%) consecutively from the Diabetes Shared Care Program and the memory clinic. These patients were followed up every 3 months with scheduled examinations. Most patients with AD were at early stage and DM was a common comorbidity (n = 42). In the DM group, there were 76 patients with subjective cognitive decline and 19 patients with mild cognitive impairment, but none sought further consultation. After adjusting for age, sex, education, and comorbidity, higher levels of glycated hemoglobin (HbA1C) were not associated with lower Mini-Mental State Examination (MMSE) scores in the DM group (coefficient: 0.03; 95% confidence interval [CI]: -0.44 to 0.50) and lower MMSE scores were not associated with higher HbA1C in the AD group either (coefficient: -0.05; 95% CI: -0.11 to 0.01). When additionally accounting for the variability of HbA1C in the DM group, higher standard deviation of HbA1C was associated with poor clock drawing test scores, but not MMSE. The coexistence of AD-DM was common, but the association between hyperglycemia and cognitive impairment was not seen in patients under regular health monitoring.

Feasibility of detecting myocardial infarction in the sheep fetus using late gadolinium enhancement CMR imaging.

BACKGROUND: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging has enabled the accurate assessment of myocardial infarction (MI). However, LGE CMR has not been performed successfully in the fetus, where it could be useful for animal studies of interventions to promote cardiac regeneration. We believe that LGE imaging could allow us to document the presence, extent and effect of MI in utero and would thereby expand our capacity for conducting fetal sheep MI research. We therefore aimed to investigate the feasibility of using LGE to detect MI in sheep fetuses. METHODS: Six sheep fetuses underwent a thoracotomy and ligation of a left anterior descending (LAD) coronary artery branch; while two fetuses underwent a sham surgery. LGE CMR was performed in a subset of fetuses immediately after the surgery and three days later. Early gadolinium enhancement (EGE) CMR was also performed in a subset of fetuses on both days. Cine imaging of the heart was performed to measure ventricular function. RESULTS: The imaging performed immediately after LAD ligation revealed no evidence of infarct on LGE (n=3). Two of four infarcted fetuses (50%) showed hypoenhancement at the infarct site on the EGE images. Three days after the ligation, LGE images revealed a clear, hyper-enhanced infarct zone in four of the five infarcted fetuses (80%). No hyper-enhanced infarct zone was seen on the one sham fetus that underwent LGE CMR. No hypoenhancement could be seen in the EGE images in either the sham (n=1) or the infarcted fetus (n=1). No regional wall motion abnormalities were apparent in two of the five infarcted fetuses. CONCLUSION: LGE CMR detected the MI three days after LAD ligation, but not immediately after. Using available methods, EGE imaging was less useful for detecting deficits in perfusion. Our study provides evidence for the ability of a non-invasive tool to monitor the progression of cardiac repair and damage in fetuses with MI. However, further investigation into the optimal timing of LGE and EGE scans and improvement of the sequences should be pursued with the aim of expanding our capacity to monitor cardiac regeneration after MI in fetal sheep.

Structure-activity relationship of daptomycin analogues with substitution at (2S, 3R) 3-methyl glutamic acid position.

Daptomycin is a highly effective lipopeptide antibiotic against Gram-positive pathogens. The presence of (2S, 3R) 3-methyl glutamic acid (mGlu) in daptomycin has been found to be important to the antibacterial activity. However the role of (2S, 3R) mGlu is yet to be revealed. Herein, we reported the syntheses of three daptomycin analogues with (2S, 3R) mGlu substituted by (2S, 3R) methyl glutamine (mGln), dimethyl glutamic acid and (2S, 3R) ethyl glutamic acid (eGlu), respectively, and their antibacterial activities. The detailed synthesis of dimethyl glutamic acid was also reported.

VITRECTOMY WITHOUT INNER LIMITING MEMBRANE PEELING FOR MACULAR RETINOSCHISIS IN HIGHLY MYOPIC EYES.

PURPOSE: To determine if it is necessary to peel inner limiting membrane during vitrectomy for macular retinoschisis in highly myopic eyes. METHODS: This retrospective noncomparative interventional case series included 112 eyes of 84 patients with myopic foveoschisis who were treated by 23-gauge 3-port pars plana vitrectomy. During vitrectomy, triamcinolone acetonide was injected into the vitreous cavity to visualize the vitreous. The inner limiting membrane was not peeled, but the posterior hyaloid membrane was removed from the macular surface with active suction or a flute needle. A fluid-gas exchange was carried out using 16% perfluoropropane gas. RESULTS: A total of 106 eyes (95%) exhibited collapse of the foveoschismatic intermediary zone after surgery. Best-corrected visual acuity at baseline and at the end of the follow-up did not differ significantly (1.06 ± 0.74 logarithm of the minimum angle of resolution versus 0.92 ± 0.56 logarithm of the minimum angle of resolution, P = 0.18). An improvement in best-corrected visual acuity of greater than 2 lines was achieved in 84 eyes (75%). A macular hole with retinal detachment was found in 6 eyes (5%) 1 to 8 months after surgery. Intraoperatively, all 112 eyes exhibited vitreous liquefaction. The posterior hyaloid membranes were tightly adherent to the posterior retinal surface and vessels except for 1 eye that had a complete posterior vitreous detachment. There were no or only a very small amount of triamcinolone acetonide particles attached to the surface of posterior retina in 38 eyes, which seemed that a completely posterior vitreous detachment had happened. But these membranes on the surface of the posterior retina can be removed easily, which indicated these membranes were posterior hyaloid membranes instead of internal limiting membranes. CONCLUSION: In the treatment of macular retinoschisis in highly myopic eyes, vitrectomy associated with posterior hyaloid membranes peeling may achieve successful anatomical results. Internal limiting membrane peeling seems unnecessary.

Posterior scleral reinforcement and vitrectomy for myopic foveoschisis in extreme myopia.

PURPOSE: To evaluate the effect of surgical posterior scleral reinforcement in extremely myopic patients (axial length ≥30 mm) with myopic foveoschisis. METHODS: The retrospective interventional case series study included patients with an axial length ≥30 mm, posterior scleral staphyloma, and myopic foveoschisis, who were treated either by posterior scleral reinforcement and 23-gauge 3-port pars plana vitrectomy (posterior scleral reinforcement group) or by vitrectomy (vitrectomy group) alone. All eyes additionally underwent cataract surgery. RESULTS: The study included 28 patients (28 eyes) with no significant (all P > 0.05) difference between the posterior scleral reinforcement group (n = 14) and the vitrectomy group (n = 14) in age, refractive error, axial length, and preoperative best-corrected visual acuity (BCVA). In addition to posterior scleral staphyloma and foveoschisis, a macular hole, a macular hole-associated retinal detachment, and a macular detachment without macular hole were present in three eyes, five eyes, and one eye, respectively in the study group and in three eyes, three eyes, and six eyes, respectively in the control group. In the study group, BCVA was significantly better after surgery than at baseline (P = 0.005) with an improvement in BCVA in 13 eyes, whereas BCVA was unchanged in 1 eye. In the control group, BCVA at baseline and at the end of follow-up did not differ significantly (P = 0.22). Gain in BCVA was marginally significantly higher in the study group than that in the control group (improvement by 0.69 ± 0.76 logMAR vs. 0.19 ± 0.54 logMAR; P = 0.05). The number of eyes with any improvement in BCVA (13 [93%] eyes vs. 11 [79%] eyes; P = 0.289) did not differ between both groups; an improvement in BCVA by more than 2 lines (10 [71%] eyes vs. 3 [21%] eyes; P = 0.009) was significantly higher in the study group than that in the control group. Anatomical success (defined as closure of macular holes and collapse of the foveoschisis) was achieved earlier in the study group (3.7 ± 3.2 months vs. 6.2 ± 3.0 months; P = 0.04). CONCLUSION: Posterior scleral reinforcement in association with vitrectomy, as compared with vitrectomy alone, was associated with a higher improvement in visual acuity in extremely myopic eyes with foveoschisis.

Serum 25-Hydroxyvitamin D Level Is Positively Associated with Vascular Reactivity Index in Patients with Type 2 Diabetes Mellitus.

Circulating 25-hydroxyvitamin D (25(OH)D) significantly influences endothelial function. This study assessed the correlation between serum 25(OH)D and endothelial function using the vascular reactivity index (VRI) in patients with type 2 diabetes mellitus (T2DM). Fasting blood samples from 102 T2DM participants and VRI were assessed. Patients were divided into three categories based on VRI: low (VRI < 1.0), intermediate (1.0 ≤ VRI < 2.0), and good (VRI ≥ 2.0). Among these patients, 30 (29.4%) had poor, 39 (38.2%) had intermediate, and 33 (32.4%) exhibited good vascular reactivity. Higher serum fasting glucose (p = 0.019), glycated hemoglobin (p = 0.009), and urinary albumin-to-creatinine ratio (p = 0.006) were associated, while lower prevalence of hypertension (p = 0.029), lower systolic blood pressure (p = 0.027), lower diastolic blood pressure (p < 0.001), and lower circulation 25(OH)D levels (p < 0.001) were associated with poor vascular reactivity. Significant independent associations between diastolic blood pressure (p = 0.002) and serum 25(OH)D level (p < 0.001) and VRI were seen in T2DM patients according to multivariable forward stepwise linear regression analysis. Serum 25(OH)D positively correlated with VRI values, and lower levels of serum 25(OH)D were linked to endothelial dysfunction in T2DM patients.

Serum Leptin Level is Positively Correlated with Aortic Stiffness in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: The global number of people living with diabetes mellitus (DM) continues to grow. Obesity, smoking, hypercholesterolemia, and hypertension are independently correlated with the risk of cardiovascular disease (CVD) in diabetic patients regardless of differences in race or ethnicity. We aimed to investigate the relationship between serum leptin levels and aortic stiffness in patients with type 2 DM to identify cardiovascular risk at the early stage. METHODS: A total of 128 diabetic patients were enrolled after screening for eligibility at a medical center in Eastern Taiwan. Aortic stiffness was defined as having a carotid-femoral pulse wave velocity (cfPWV) of >10 m/s using applanation tonometry. Fasting serum levels of leptin and other associated biomarkers were determined by enzyme immunoassay or biochemical analyses. RESULTS: Forty-six diabetic patients with a cfPWV of >10 m/s were included in the aortic stiffness group. Compared with the control group (n = 82), our aortic stiffness group was significantly older (p = 0.019) and had higher body fat mass (p = 0.002), systolic blood pressure (SBP) (p < 0.001), serum triglyceride (p = 0.02), and serum leptin (p < 0.001). Aortic stiffness was also associated with insulin resistance (p = 0.026) and poorer blood sugar control (higher fasting glucose (p = 0.044) and glycated hemoglobin (HbA1c) (p = 0.049)). In the multivariable linear regression analyses examining the correlations between aortic stiffness and clinical variables, we found that age (ß = 0.291; p < 0.001), SBP (ß = 0.176; p = 0.033), logarithmically transformed urinary albumin-creatinine ratio (ß = 0.256; p = 0.002), and serum leptin levels (ß = 0.244; p = 0.002) were independently associated with cfPWV values. The analyses showed that only leptin was correlated with a higher probability of aortic stiffness (odds ratio: 1.055, 95% confidence interval: 1.005-1.107, p = 0.031). CONCLUSIONS: The results suggested that serum leptin is positively associated with aortic stiffness in patients with type 2 DM.

Serum sclerostin level is positively associated with endothelial dysfunction measured by digital thermal monitoring in patients with type 2 diabetes: A prospective cross-sectional study.

Sclerostin and dickkopf-1 (DKK1), extracellular inhibitors of the canonical Wnt/ß-catenin signaling pathway, have been associated with vascular aging and atherosclerosis. This study aimed to assess the correlation of sclerostin and DKK1 concentrations with endothelial function measured using vascular reactivity index (VRI) in patients with type 2 diabetes mellitus (T2DM). Fasting blood samples were collected from 100 patients with T2DM. Endothelial function and VRI were measured using digital thermal monitoring and circulating sclerostin and DKK1 levels by enzyme-linked immunosorbent assays. VRI values < 1.0, 1.0-1.9, and > 2.0 indicated poor, intermediate, and good vascular reactivity, respectively. Overall, 30, 38, and 32 patients had poor, intermediate, and good vascular reactivity, respectively. Older age, higher serum glycated hemoglobulin, urinary albumin-to-creatinine ratio, and sclerostin as well as lower hypertension prevalence, systolic blood pressure, and diastolic blood pressure (DBP) were associated with poor VRI. Multivariable forward stepwise linear regression analysis showed that DBP (ß = 0.294, adjusted R2 change = 0.098, P < .001), log-glycated hemoglobin (ß = -0.235, adjusted R2 change = 0.050, P = .002), log-urine albumin-to-creatinine ratio (ß = -0.342, adjusted R2 change = 0.227, P < .001), and log-sclerostin level (ß = -0.327, adjusted R2 change = 0.101, P < .001) were independently associated with VRI. Serum sclerostin, along with glycated hemoglobin and albumin-to-creatinine ratio, exhibited a negative correlation with VRI, while DBP showed a positive correlation with VRI. These factors can independently predict endothelial dysfunction in patients with T2DM.

Synthesis and cytotoxicity of 3,4-disubstituted-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazoles and novel 5,6-dihydro-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives bearing 3,4,5-trimethoxyphenyl moiety.

A series of 3,4-disubstituted-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazoles and some novel 5,6-dihydro-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles bearing 3,4,5-trimethoxyphenyl moiety were synthesized and screened for their anticancer activity. The preliminary bioassay results indicated that compounds 14 and 16 showed much stronger cytotoxicity than Doxorubicin against HepG2 cell lines with IC(50) values of 0.58 and 3.17 µM, respectively. Meanwhile compound 16 also exhibited a broad spectrum of antitumor activity against MCF-7 and MKN45 with IC(50) values of 10.92 and 13.79 µM, respectively.

[Research advances in antitumor activities of pyrimidine derivatives].

Pyrimidine derivatives have been the subject of much attention in pesticide and medicine fields owing to their unique biological properties. Particularly, a large number of these compounds have recently been reported to show substantial antitumor activities, and some of them have been investigated in clinical trials. Although these structurally novel compounds have a common chemical moiety of a pyrimidine ring, there are a variety of mechanisms of their antitumor action, such as, inhibition of cyclin-dependent-kinases, inhibition of protein tyrosine kinase, inhibition of carbonic anhydrases, inhibition of dihydrofolate reductase and disruption of microtubule assembly. In this paper, we described the latest advances in the research of such pyrimidine derivatives as antitumor drug according to their action on targets.

[Chloroplast genome phylogeny and codon preference of Docynia longiunguis].

Docynia longiunguis is a plant uniquely present in China and is of high edible and medicinal value. The analysis of its chloroplast genome will help clarify the phylogenetic relationship among Docynia and facilitate the development and utilization of D. longiunguis resources. Based on the alignment of chloroplast genome sequences of related species, the phylogeny and codon preference were analyzed. The total length of D. longiunguis chloroplast genome sequence was 158 914 bp (GenBank accession number is MW367027), with an average GC content of 36.7%. The length of the large single-copy (LSC), the small single-copy (SSC), and inverted repeats (IRs) are 87 020 bp, 19 156 bp, and 26 369 bp, respectively. A total of 102 functional genes were annotated, including 72 protein-coding genes, 26 tRNA genes, and 4 rRNA genes. The best model for constructing phylogenetic tree was TVM+F+R2. D. longiunguis and Docynia indica were clustered into a single group, while Docynia and Malus were clustered into a single group. Comparison of the chloroplast genome sequences of D. longiunguis and its five related species revealed that trnY (GUA)-psbD, ndhC-trnV (UAC), accD-psaI, psbZ-trnfM (CAU), ndhF-trnL gene regions varied greatly. The nucleic acid diversity analysis showed that there were 11 high variation areas with nucleotide variability > 0.01, all were located in the LSC and SSC regions. Except for D. longiunguis, the trnH genes in other sequences were located at the IRs/LSC junction and did not cross the boundary. Codon preference analysis showed that D. longiunguis chloroplast genome has the largest number of isoleucine (Ile) codons, up to 1 205. D. longiunguis has the closest genetic relationship with Malus baccata, Malus sieboldii, Malus hupehensis and Chaenomeles sinensis. Its chloroplast genome codon prefers to end with A/T. The chloroplast genome of D. longiunguis and other Rosaceae chloroplast genomes showed great differences in gene distribution in four boundary regions, while relatively small differences from the chloroplast genomes of Docynia delavayi and D. indica of the same genus were observed. The genome annotation, phylogenetic analysis and sequence alignment of chloroplast genome of D. longiunguis may facilitate the identification, development and utilization of this species.