Synthesis of Multisubstituted 1,2,3-Triazoles: Regioselective Formation and Reaction Mechanism.

A synthetically useful approach to functionalized triazoles is described via the reaction of ß-carbonyl phosphonates and azides. 1,4- and 1,5-disubstituted and 1,4,5-trisubstituted triazoles can be regio- and chemoselectively accessed under mild conditions in good to excellent yields (31 examples, up to 99%). A mechanism is proposed that rationalizes the avoidance of the 4-phosphonate byproducts, which is aligned with crystallographic and experimental evidence.

Costs and Cardiovascular Benefits of a Fourth-Generation Synchronous Telehealth Program on Mortality and Cardiovascular Outcomes for Patients With Atrial Fibrillation: Retrospective Cohort Study.

BACKGROUND: The prevalence of atrial fibrillation (AF) continues to increase in modern aging society. Patients with AF are at high risk for multiple adverse cardiovascular events, including heart failure, stroke, and mortality. Improved medical care is needed for patients with AF to enhance their quality of life and limit their medical resource utilization. With advances in the internet and technology, telehealth programs are now widely used in medical care. A fourth-generation telehealth program offers synchronous and continuous medical attention in response to physiological parameters measured at home. Although we have previously shown the benefits of this telehealth program for some patients with a high risk of cardiovascular disease, its benefits for patients with AF remains uncertain. OBJECTIVE: This study aims to investigate the benefits of participating in a fourth-generation telehealth program for patients with AF in relation to cardiovascular outcomes. METHODS: This was a retrospective cohort study. We retrospectively searched the medical records database of a tertiary medical center in Northern Taiwan between January 2007 and December 2017. We screened 5062 patients with cardiovascular disease and enrolled 537 patients with AF, of which 279 participated in the telehealth program and 258 did not. Bias was reduced using the inverse probability of treatment weighting adjustment based on the propensity score. Outcomes were collected and analyzed, including all-cause readmission, admission for heart failure, acute coronary syndrome, ischemic stroke, systemic embolism, bleeding events, all-cause mortality, and cardiovascular death within the follow-up period. Total medical expenses and medical costs in different departments were also compared. Subgroup analyses were conducted on ischemic stroke stratified by several subgroup variables. RESULTS: The mean follow-up period was 3.0 (SD 1.7) years for the telehealth group and 3.4 (SD 1.9) years for the control group. After inverse probability of treatment weighting adjustment, the patients in the telehealth program had significantly fewer ischemic strokes (2.0 vs 4.5 events per 100 person-years; subdistribution hazard ratio [SHR] 0.45, 95% CI 0.22-0.92) and cardiovascular deaths (2.5 vs 5.9 events per 100 person-years; SHR 0.43, 95% CI 0.18-0.99) at the follow-up. The telehealth program particularly benefited patients comorbid with vascular disease (SHR 0.11, 95% CI 0.02-0.53 vs SHR 1.16, 95% CI 0.44-3.09; P=.01 for interaction). The total medical expenses during follow-up were similar in the telehealth and control groups. CONCLUSIONS: This study demonstrated the benefits of participating in the fourth-generation telehealth program for patients with AF by significantly reducing their ischemic stroke risk while spending the same amount on medical expenses.

Correction: Effect of Telehealth Services on Mitral and Tricuspid Regurgitation Progression: Retrospective Study.

[This corrects the article DOI: 10.2196/47947.].

Effect of Telehealth Services on Mitral and Tricuspid Regurgitation Progression: Retrospective Study.

BACKGROUND: Mitral regurgitation (MR) and tricuspid regurgitation (TR) are common cardiac conditions with high mortality risks, which can be improved through early intervention. Telehealth services, which allow for remote monitoring of patient conditions, have been proven to improve the health management of chronic diseases, but the effects on MR and TR progression are unknown. OBJECTIVE: This study aimed to explore whether patients receiving telehealth services have less MR and TR progression compared with a control group. We also aimed to identify the determinants of MR and TR progression. METHODS: This single-center retrospective study conducted at the National Taiwan University Hospital compared MR and TR progression (defined as either progression to moderate or greater MR and TR or MR and TR progression by ≥2 grades during the study period) between the telehealth and control groups. Patients had a minimum of 2 transthoracic echocardiograms at least 6 months apart; baseline mild-moderate MR and TR or lower; and no prior surgeries on the mitral or tricuspid valve. Telehealth patients were defined as those who received telehealth services for at least 28 days within 3 months of baseline. Basic demographics, baseline blood pressure measurements, prescribed medication, and Charlson Comorbidity Index components were obtained for all patients. RESULTS: A total of 1081 patients (n=226 in the telehealth group and n=855 in the control group) were included in the study analyses. The telehealth group showed significantly lower baseline systolic blood pressure (P<.001), higher Charlson Comorbidity Index (P=.02), higher prevalence of prior myocardial infarction (P=.01) and heart failure (P<.001), higher beta-blocker (P=.03) and diuretic (P=.04) use, and lower nitrate use (P=.04). Both groups showed similar cardiac remodeling conditions at baseline. Telehealth was found to be neutral for both MR (hazard ratio 1.10, 95% CI 0.80-1.52; P=.52) and TR (hazard ratio 1.27, 95% CI 0.92-1.74; P=.14) progression. Determinants for moderate or greater MR progression included older age, female sex, diuretic use, larger left atrial dimension, left ventricular end-diastolic dimension, left ventricular end-systolic dimension, and lower left ventricular ejection fraction. Determinants of moderate or greater TR progression included older age, female sex, diuretic use, presence of atrial fibrillation, LA dimension, left ventricular end-systolic dimension, and lower left ventricular ejection fraction; statin use was found to be protective. CONCLUSIONS: This is the first study to assess the association between telehealth services and the progression of MR and TR. Telehealth patients, who had more comorbidities, displayed similar MR and TR progression versus control patients, indicating that telehealth may slow MR and TR progression. Determinants of MR and TR progression included easy-to-measure traditional echo parameters of cardiac function, older age, female sex, and atrial fibrillation, which can be incorporated into a telehealth platform and advanced alert system, improving patient outcomes through personalized care.

Population and Conservation Status of the Flying Fox Pteropus dasymallus in Taiwan.

Pteropus dasymallus is widely distributed on islands throughout the western edge of the Pacific Ocean. The Formosan flying fox, P. d. formosus, is an endemic subspecies in Taiwan found mainly on Lyudao; it was previously thought to have been extirpated. Since 2005, intensive surveys have been conducted to investigate the residency, population size and plant resource utilization of P. dasymallus in Taiwan. Interviews were carried out to investigate its former abundance and the causes of population decline. In Taiwan, P. dasymallus is in a state of ongoing oceanic dispersal and colonization and has considerably expanded its geographic range. In addition to remaining in its historic habitat on Lyudao, P. dasymallus has also established colonies on Gueishan Island and in Hualien on Taiwan's main island in the past few decades. The total population size is estimated to be 240 individuals, and this number is on the rise. Approximately three-quarters of the entire population (73.64%) was found on Gueishan Island. The sex ratio was strongly skewed toward males. A total of 40 plant species were recorded as being used by the flying fox for food, roosts or perches. More agricultural and horticultural plant species were used by the flying fox in urban Hualien. According to the interviews, flying foxes were abundant on Lyudao, but their number dramatically declined from the 1970s to the mid-1980s, mainly due to commercial hunting. Maintaining a sufficient population size and genetic variability is fundamental to the long-term survival of the flying fox. Enforcing conservation laws, restoring habitats, controlling invasive species and improving public awareness are the main steps in the recovery and sustainability of the flying fox population.

Nutrient status regulates MED19a phase separation for ORESARA1-dependent senescence.

The mediator complex is highly conserved in eukgaryotes and is integral for transcriptional responses. Mediator subunits associate with signal-responsive transcription factors (TF) to activate expression of specific signal-responsive genes. As the key TF of Arabidopsis thaliana senescence, ORESARA1 (ORE1) is required for nitrogen deficiency (-N) induced senescence; however, the mediator subunit that associates with ORE1 remains unknown. Here, we show that Arabidopsis MED19a associates with ORE1 to activate -N senescence-responsive genes. Disordered MED19a forms inducible nuclear condensates under -N that is regulated by decreasing MED19a lysine acetylation. MED19a carboxyl terminus (cMED19a) harbors a mixed-charged intrinsically disordered region (MC-IDR) required for ORE1 interaction and liquid-liquid phase separation (LLPS). Plant and human cMED19 are sufficient to form heterotypic condensates with ORE1. Human cMED19 MC-IDR, but not yeast cMED19 IDR, partially complements med19a suggesting functional conservation in evolutionarily distant eukaryotes. Phylogenetic analysis of eukaryotic cMED19 revealed that the MC-IDR could arise through convergent evolution. Our result of MED19 MC-IDR suggests that plant MED19 is regulated by phase separation during stress responses.

Tissue-specific transcriptomic analysis uncovers potential roles of natural antisense transcripts in Arabidopsis heat stress response.

Natural antisense transcripts (NATs) are an important class of non-coding ribonucleic acids (RNAs) that have been shown to regulate gene expression. Using strand-specific RNA sequencing, 36,317 NAT pairs were identified, and 5,536 were specifically expressed under heat stress. We found distinct expression patterns between vegetative and reproductive tissues for both coding genes and genes encoding NATs. Genes for heat-responsive NATs are associated with relatively high levels of H3K4me3 and low levels of H3K27me2/3. On the other hand, small RNAs are significantly enriched in sequence overlapping regions of NAT pairs, and a large number of heat-responsive NATs pairs serve as potential precursors of nat-siRNAs. Collectively, our results suggest epigenetic modifications and small RNAs play important roles in the regulation of NAT expression, and highlight the potential significance of heat-inducible NATs.

The Logistics of Medication and Patient Flow in Video-Based Virtual Clinics During a Sudden COVID-19 Outbreak in Taiwan: Observational Study.

BACKGROUND: The COVID-19 pandemic was well controlled in Taiwan until an outbreak in May 2021. Telemedicine was rapidly implemented to avoid further patient exposure and to unload the already burdened medical system. OBJECTIVE: To understand the effect of COVID-19 on the implementation of video-based virtual clinic visits during this outbreak, we analyzed the logistics of prescribing medications and patient flow for such virtual visits at a tertiary medical center. METHODS: We retrospectively collected information on video-based virtual clinic visits and face-to-face outpatient visits from May 1 to August 31, 2021, from the administrative database at National Taiwan University Hospital. The number of daily new confirmed COVID-19 cases in Taiwan was obtained from an open resource. RESULTS: There were 782 virtual clinic visits during these 3 months, mostly for the departments of internal medicine, neurology, and surgery. The 3 most common categories of medications prescribed were cardiovascular, diabetic, and gastrointestinal, of which cardiovascular medications comprised around one-third of all medications prescribed during virtual clinic visits. The number of virtual clinic visits was significantly correlated with the number of daily new confirmed COVID-19 cases, with approximately a 20-day delay (correlation coefficient 0.735; P<.001). The patient waiting time for video-based virtual clinic visits was significantly shorter compared with face-to-face clinic visits during the same period (median 3, IQR 2-6 min vs median 20, IQR 9-42 min; rank sum P<.001). Although the time saved was appreciated by the patients, online payment with direct delivery of medications without the need to visit a hospital was still their major concern. CONCLUSIONS: Our data showed that video-based virtual clinics can be implemented rapidly after a COVID-19 outbreak. The virtual clinics were efficient, as demonstrated by the significantly reduced waiting time. However, there are still some barriers to the large-scale implementation of video-based virtual clinics. Better preparation is required to improve performance in possible future large outbreaks.

The Association Between Short-term Exposure to Ambient Air Pollution and Patient-Level Home Blood Pressure Among Patients With Chronic Cardiovascular Diseases in a Web-Based Synchronous Telehealth Care Program: Retrospective Study.

BACKGROUND: The association between short-term exposure to ambient air pollution and blood pressure has been inconsistent, as reported in the literature. OBJECTIVE: This study aimed to investigate the relationship between short-term ambient air pollution exposure and patient-level home blood pressure (HBP). METHODS: Patients with chronic cardiovascular diseases from a telehealth care program at a university-affiliated hospital were enrolled as the study population. HBP was measured by patients or their caregivers. Hourly meteorological data (including temperature, relative humidity, wind speed, and rainfall) and ambient air pollution monitoring data (including CO, NO2, particulate matter with a diameter of <10 µm, particulate matter with a diameter of <2.5 µm, and SO2) during the same time period were obtained from the Central Weather Bureau and the Environmental Protection Administration in Taiwan, respectively. A stepwise multivariate repeated generalized estimating equation model was used to assess the significant factors for predicting systolic and diastolic blood pressure (SBP and DBP). RESULTS: A total of 253 patients and 110,715 HBP measurements were evaluated in this study. On multivariate analysis, demographic, clinical, meteorological factors, and air pollutants significantly affected the HBP (both SBP and DBP). All 5 air pollutants evaluated in this study showed a significant, nonlinear association with both home SBP and DBP. Compared with demographic and clinical factors, environmental factors (meteorological factors and air pollutants) played a minor yet significant role in the regulation of HBP. CONCLUSIONS: Short-term exposure to ambient air pollution significantly affects HBP in patients with chronic cardiovascular disease.

The Costs and Cardiovascular Benefits in Patients With Peripheral Artery Disease From a Fourth-Generation Synchronous Telehealth Program: Retrospective Cohort Study.

BACKGROUND: Patients with peripheral artery disease (PAD) are at high risk for major cardiovascular events, including myocardial infarction, stroke, and hospitalization for heart failure. We have previously shown the clinical efficacy of a fourth-generation synchronous telehealth program for some patients, but the costs and cardiovascular benefits of the program for PAD patients remain unknown. OBJECTIVE: The telehealth program is now widely used by higher-risk cardiovascular patients to prevent further cardiovascular events. This study investigated whether patients with PAD would also have better cardiovascular outcomes after participating in the fourth-generation synchronous telehealth program. METHODS: This was a retrospective cohort study. We screened 5062 patients with cardiovascular diseases who were treated at National Taiwan University Hospital and then enrolled 391 patients with a diagnosis of PAD. Of these patients, 162 took part in the telehealth program, while 229 did not and thus served as control patients. Inverse probability of treatment weighting (IPTW) based on the propensity score was used to mitigate possible selection bias. Follow-up outcomes included heart failure hospitalization, acute coronary syndrome, stroke, and all-cause readmission during the 1-year follow-up period and through the last follow-up. RESULTS: The mean follow-up duration was 3.1 (SD 1.8) years for the patients who participated in the telehealth program and 3.2 (SD 1.8) for the control group. The telehealth program patients exhibited lower risk of ischemic stroke than did the control group in the first year after IPTW (0.9% vs 3.5%; hazard ratio [HR] 0.24; 95% CI 0.07-0.80). The 1-year composite endpoint of vascular accident, including acute coronary syndrome and stroke, was also significantly lower in the telehealth program group after IPTW (2.4% vs 5.2%; HR 0.46; 95% CI 0.21-0.997). At the end of the follow-up, the telehealth program group continued to exhibit a significantly lower rate of ischemic stroke than did the control group after IPTW (0.9% vs 3.5%; HR 0.52, 95% CI 0.28-0.93). Furthermore, the medical costs of the telehealth program patients were not higher than those of the control group, whether in terms of outpatient, emergency department, hospitalization, or total costs. CONCLUSIONS: The PAD patients who participated in the fourth-generation synchronous telehealth program exhibited lower risk of ischemic stroke events over both mid- and long-term follow-up periods. However, larger-scale and prospective randomized clinical trials are needed to confirm our findings.

Cajanolactone A, a stilbenoid from Cajanus cajan, inhibits energy intake and lipid synthesis/storage, and promotes energy expenditure in ovariectomized mice.

BACKGROUND: We had reported that cajanolactone A (CLA) from Cajanus cajan dose-dependently inhibited ovariectomy-induced obesity and liver steatosis in mice, showing potential to prevent postmenopausal obesity and fatty liver. In this study, the role of CLA in the regulation of energy and lipid homeostasis was investigated. METHODS: Ovariectomized mice treated with CLA or vehicle for 12 weeks were performed a 48 h monitoring for energy metabolism and food uptake. After that, hypothalami, perigonadal (pWATs), inguinal (iWATs) and brown (BATs) adipose tissues, livers, sera, and fecal and cecal contents were collected and analyzed. FINDINGS: In CLA-treated mice, we observed reduced food uptake; increased energy expenditure; inhibited expression of orexigenic genes (ORX, ORXR2, pMCH and Gal) in the hypothalami, of lipogenic genes (CD36, SREBP-1c, ChREBP, PPARγ) in the livers, and of lipid storage proteins in the WATs (FSP27, MEST and caveolin-1) and livers (FSP27, Plin2 and Plin5); stimulated expression of metabolism-related proteins (pATGL and Echs1) in the adipose tissues and of thermogenic protein (UCP1) in the inguinal WATs; increased BAT content; increased mitochondria in the pWATs and livers; inhibited angiogenesis in the pWATs; and altered gut microbiome diversity with an increased abundance of Bacteroides. INTERPRETATION: CLA prevents ovariectomy-induced obesity and liver steatosis via regulating energy intake and lipid synthesis/storage, promoting UCP1-dependent heat production, and protecting the mitochondrial function of hepatocytes and adipocytes. The improved gut microecology and inhibited angiogenesis may also contribute to the anti-obese activity of CLA.

Altered gene expression in glycolysis-cholesterol synthesis axis correlates with outcome of triple-negative breast cancer.

Identification of molecular subtypes of clinically resectable triple-negative breast cancer (TNBC) is of great importance to achieve better clinical outcomes. Inter- and intratumor metabolic heterogeneity improves cancer survival, and the interaction of various metabolic pathways may affect treatment outcome of TNBC. We speculated that TNBC can be categorized into prognostic metabolic subtype according to the expression changes of glycolysis and cholesterol synthesis. The genome, transcriptome, and clinical data were downloaded from the Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium and subsequently analyzed by integrated bioinformatics methods. Four subtypes, namely, glycolytic, cholesterogenic, quiescent, and mixed, were classified according to the normalized median expressions of the genes involved in glycolysis and cholesterol synthesis. In the four subtypes, the cholesterogenic type was correlated with the shortest median survival (log rank P = 0.044), while patients with high-expressed glycolytic genes tended to have a longer survival. Tumors with PIK3CA amplification and dynein axonemal heavy chain 2 deletion exhibited higher expressions of cholesterogenic genes than other mutant oncogenes. The expressions of mitochondrial pyruvate carrier MPC1 and MPC2 were the lowest in quiescent tumor, and MPC2 expression was higher in cholesterogenic tumor compared with glycolytic or quiescent tumor (t-test P < 0.001). Glycolytic and cholesterogenic gene expressions were related to the expressions of prognostic genes in some other types of cancers. Classification of glycolytic and cholesterogenic pathways according to metabolic characteristics provides a new understanding to previously identified subtypes of TNBC and could improve personalized treatments based on tumor metabolic profiles.

[Effect of CPEB4 on Migration and Cycle of Chronic Myeloid Leukemia Cell].

OBJECTIVE: To investigate the effects of CPEB4 on the migration and cycle of K562 cells and the changes of protein molecules that may be involved in the regulatory mechanism. METHODS: Western blot was used to detect the expression of CPEB4 in normal leukocytes and K562 cells. The overexpression plasmid pcDNA3.1(+)-His-CPEB4, silencing plasmid pPLK+Puro-CPEB4 shRNA were transfected into K562 cells by electroporation so as to change CPEB4. The transfection efficiency was detected by Western blot. Finally, the migration and cycle of different cells were detected by Transwell chamber and flow cytometry.Western blot was used to detect the expression changes of MMP2, MMP9, CDK4, CyclinD1 and P21 proteins. RESULTS: Compared with normal white blood cells, the expression of CPEB4 protein in K562 cells was significantly enhanced (P＜0.01); Compared with the control group, CPEB4-silenced K562 cells showed that the cell migration ability was significantly enhanced (P＜0.01); G0/G1 phase cell ratio reduced, G2/M phase cell ratio increased, and cell cycle progression accelerated（P＜0.01）, The expression levels of MMP2 (P＜0.05), MMP9 (P＜0.05), CDK4 (P＜0.01), CyclinD1 (P＜0.01) proteins increased significantly. The expression level of P21 protein significantly decreased (P＜0.01). The migration ability of K562 cells after CPEB4 overexpression was decreased (P＜0.01), the cell ratio of G0/G1 phase in the cell cycle increased, the cell proportion of S phase decreased and the cell cycle progression was arrested at G0/G1 phase (P＜0.01). The expression of P21 protein increased, MMP2 , MMP9, CDK4, CyclinD1 protein expression decreased significantly（P＜0.05-0.01）. CONCLUSION: CPEB4 can inhibit the migration of K562 cells and arrest cell cycle progression at G0/G1 phase. Its mechanism may be related with regulating the exprossion of MMP2, MMP9, CDK4, CyclinD1 and P21 proteins.

[Effect of CPEB4 on Proliferation and Apoptosis of Chronic Myeloid Leukemia Cells].

OBJECTIVE: To explore the expression of CPEB4 in K562 cells, the biological activity and its possible molecular mechanisms. METHODS: Western blot was used to detect the expression of CPEB4 in normal leukocytes and K562 cells. The overexpression plasmid pcDNA3.1(+)-His-CPEB4 and the silencing plasmid pPLK+Puro-CPEB4 shRNA were transfected into K562 cells to change the expression of CPEB4 in K562 cells, and the transfection efficiency was detected by Western blot. Finally, CCK-8 and flow cytometry were used to detect the proliferation and apoptosis of differently treated cells, and the expression changes of proliferation and apoptosis marker proteins (AKT, p-AKT, caspase-3, BCL-2) were detected by Western blot. RESULTS: Compared with normal leukocytes, the expression of CPEB4 protein in K562 cells was higher (P＜0.01). Compared with the control group, the proliferation of CPEB4-silenced K562 cells significantly increased (P＜0.01), the number of apoptotic cell significantly decreased, and expression of AKT, p-AKT and BCL-2 was significantly increased, the protein expression of caspase-3 was significantly reduced. The proliferation of K562 cells after CPEB4 overexpression was slowed down (P＜0.05), the number of apoptotic cells significantly increased,the expressions of AKT, p-AKT and BCL-2 were significantly down-regulated, and the expression of caspase-3 was up-regulated. CONCLUSION: CPEB4 can inhibit the proliferation and promote the apoptosis of K562 cells, the AKT, p-AKT, BCL-2 and caspase-3 are involved in the regulation mechanism.

Assessment of the Relationship Between Ambient Temperature and Home Blood Pressure in Patients From a Web-Based Synchronous Telehealth Care Program: Retrospective Study.

BACKGROUND: Decreased ambient temperature significantly increases office blood pressure, but few studies have evaluated the effect of ambient temperature on home blood pressure. OBJECTIVE: We aimed to investigate the relationship between short-term ambient temperature exposure and home blood pressure. METHODS: We recruited patients with chronic cardiovascular diseases from a telehealth care program at a university-affiliated hospital. Blood pressure was measured at home by patients or their caregivers. We obtained hourly meteorological data for Taipei (temperature, relative humidity, and wind speed) for the same time period from the Central Weather Bureau, Taiwan. RESULTS: From 2009 to 2013, we enrolled a total of 253 patients. Mean patient age was 70.28 (SD 13.79) years, and 66.0% (167/253) of patients were male. We collected a total of 110,715 home blood pressure measurements. Ambient temperature had a negative linear effect on all 3 home blood pressure parameters after adjusting for demographic and clinical factors and antihypertensive agents. A 1°C decrease was associated with a 0.5492-mm Hg increase in mean blood pressure, a 0.6841-mm Hg increase in systolic blood pressure, and a 0.2709-mm Hg increase in diastolic blood pressure. This temperature effect on home blood pressure was less prominent in patients with diabetes or hypertension. Antihypertensive agents modified this negative effect of temperature on home blood pressure to some extent, and angiotensin receptor blockers had the most favorable results. CONCLUSIONS: Short-term exposure to low ambient temperature significantly increased home blood pressure in patients with chronic cardiovascular diseases. Antihypertensive agents may modify this effect.

A noncoding RNA transcribed from the AGAMOUS (AG) second intron binds to CURLY LEAF and represses AG expression in leaves.

Dispersed H3K27 trimethylation (H3K27me3) of the AGAMOUS (AG) genomic locus is mediated by CURLY LEAF (CLF), a component of the Polycomb Repressive Complex (PRC) 2. Previous reports have shown that the AG second intron, which confers AG tissue-specific expression, harbors sequences targeted by several positive and negative regulators. Using RACE reverse transcription polymerase chain reaction, we found that the AG intron 2 encodes several noncoding RNAs. RNAi experiment showed that incRNA4 is needed for CLF repressive activity. AG-incRNA4RNAi lines showed increased leaf AG mRNA levels associated with a decrease of H3K27me3 levels; these plants displayed AG overexpression phenotypes. Genetic and biochemical analyses demonstrated that the AG-incRNA4 can associate with CLF to repress AG expression in leaf tissues through H3K27me3-mediated repression and to autoregulate its own expression level. The mechanism of AG-incRNA4-mediated repression may be relevant to investigations on tissue-specific expression of Arabidopsis MADS-box genes.

Effect of Contract Compliance Rate to a Fourth-Generation Telehealth Program on the Risk of Hospitalization in Patients With Chronic Kidney Disease: Retrospective Cohort Study.

BACKGROUND: Chronic kidney disease (CKD) is prevalent in Taiwan and it is associated with high all-cause mortality. We have shown in a previous paper that a fourth-generation telehealth program is associated with lower all-cause mortality compared to usual care with a hazard ratio of 0.866 (95% CI 0.837-0.896). OBJECTIVE: This study aimed to evaluate the effect of renal function status on hospitalization among patients receiving this program and to evaluate the relationship between contract compliance rate to the program and risk of hospitalization in patients with CKD. METHODS: We retrospectively analyzed 715 patients receiving the telehealth care program. Contract compliance rate was defined as the percentage of days covered by the telehealth service before hospitalization. Patients were stratified into three groups according to renal function status: (1) normal renal function, (2) CKD, or (3) end-stage renal disease (ESRD) and on maintenance dialysis. The outcome measurements were first cardiovascular and all-cause hospitalizations. The association between contract compliance rate, renal function status, and hospitalization risk was analyzed with a Cox proportional hazards model with time-dependent covariates. RESULTS: The median follow-up duration was 694 days (IQR 338-1163). Contract compliance rate had a triphasic relationship with cardiovascular and all-cause hospitalizations. Patients with low or very high contract compliance rates were associated with a higher risk of hospitalization. Patients with CKD or ESRD were also associated with a higher risk of hospitalization. Moreover, we observed a significant interaction between the effects of renal function status and contract compliance rate on the risk of hospitalization: patients with ESRD, who were on dialysis, had an increased risk of hospitalization at a lower contract compliance rate, compared with patients with normal renal function or CKD. CONCLUSIONS: Our study showed that there was a triphasic relationship between contract compliance rate to the telehealth program and risk of hospitalization. Renal function status was associated with risk of hospitalization among these patients, and there was a significant interaction with contract compliance rate.

Potyviral Gene-Silencing Suppressor HCPro Interacts with Salicylic Acid (SA)-Binding Protein 3 to Weaken SA-Mediated Defense Responses.

The viral infection process is a battle between host defense response and pathogen antagonizing action. Several studies have established a tight link between the viral RNA silencing suppressor (RSS) and the repression of salicylic acid (SA)-mediated defense responses, nonetheless host factors directly linking an RSS and the SA pathway remains unidentified. From yeast two-hybrid analysis, we identified an interaction between the potyviral RSS helper-component proteinase (HCPro) and SA-binding protein SABP3. Co-localization and bimolecular fluorescence complementation analyses validated the direct in vivo interaction between Turnip mosaic virus (TuMV) HCPro and the Arabidopsis homologue of SABP3, AtCA1. Additionally, transient expression of TuMV HCPro demonstrated its ability to act as a negative regulator of AtCA1. When the plants of the AtCA1 knockout mutant line were inoculated with TuMV, our results indicated that AtCA1 is essential to restrict viral spreading and accumulation, induce SA accumulation, and trigger the SA pathway. Unexpectedly, the AtCA1 overexpression line also displayed a similar phenotype, suggesting that the constitutive expression of AtCA1 antagonizes the SA pathway. Taken together, our results depict AtCA1 as an essential regulator of SA defense responses. Moreover, the interaction of potyviral HCPro with this regulator compromises the SA pathway to weaken host defense responses and facilitate viral infection.

CURLY LEAF Regulates Gene Sets Coordinating Seed Size and Lipid Biosynthesis.

CURLY LEAF (CLF), a histone methyltransferase of Polycomb Repressive Complex 2 (PRC2) for trimethylation of histone H3 Lys 27 (H3K27me3), has been thought as a negative regulator controlling mainly postgermination growth in Arabidopsis (Arabidopsis thaliana). Approximately 14% to 29% of genic regions are decorated by H3K27me3 in the Arabidopsis genome; however, transcriptional repression activities of PRC2 on a majority of these regions remain unclear. Here, by analysis of transcriptome profiles, we found that approximately 11.6% genes in the Arabidopsis genome were repressed by CLF in various organs. Unexpectedly, approximately 54% of these genes were preferentially repressed in siliques. Further analyses of 118 transcriptome datasets uncovered a group of genes that was preferentially expressed and repressed by CLF in embryos at the mature-green stage. This observation suggests that CLF mediates a large-scale H3K27me3 programming/reprogramming event during embryonic development. Plants of clf-28 produced bigger and heavier seeds with higher oil content, larger oil bodies, and altered long-chain fatty acid composition compared with wild type. Around 46% of CLF-repressed genes were associated with H3K27me3 marks; moreover, we verified histone modification and transcriptional repression by CLF on regulatory genes. Our results suggest that CLF silences specific gene expression modules. Genes operating within a module have various molecular functions, but they cooperate to regulate a similar physiological function during embryo development.

Analysis of non-coding transcriptome in rice and maize uncovers roles of conserved lncRNAs associated with agriculture traits.

Long non-coding RNAs (lncRNAs) have recently been found to widely exist in eukaryotes and play important roles in key biological processes. To extend our knowledge of lncRNAs in crop plants we performed both non-directional and strand-specific RNA-sequencing experiments to profile non-coding transcriptomes of various rice and maize organs at different developmental stages. Analysis of more than 3 billion reads identified 22 334 long intergenic non-coding RNAs (lincRNAs) and 6673 pairs of sense and natural antisense transcript (NAT). Many lincRNA genes were associated with epigenetic marks. Expression of rice lincRNA genes was significantly correlated with that of nearby protein-coding genes. A set of NAT genes also showed expression correlation with their sense genes. More than 200 rice lincRNA genes had homologous non-coding sequences in the maize genome. Much more lincRNA and NAT genes were derived from conserved genomic regions between the two cereals presenting positional conservation. Protein-coding genes flanking or having a sense-antisense relationship to these conserved lncRNA genes were mainly involved in development and stress responses, suggesting that the associated lncRNAs might have similar functions. Integrating previous genome-wide association studies (GWAS), we found that hundreds of lincRNAs contain trait-associated SNPs (single nucleotide polymorphisms [SNPs]) suggesting their putative contributions to developmental and agriculture traits.