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Hutchinson-Gilford progeria syndrome is a premature aging disease caused by LMNA gene mutation and the production of a truncated prelamin A protein “progerin” that elicits cellular and organismal toxicity. Progerin accumulates in the vasculature, being especially detrimental for vascular smooth muscle cells (VSMC). Vessel stiffening and aortic atherosclerosis in HGPS patients are accompanied by VSMC depletion in the medial layer, altered extracellular matrix (ECM), and thickening of the adventitial layer. Mechanisms whereby progerin causes massive VSMC loss and vessel alterations remain poorly understood. Mature VSMC retain phenotypic plasticity and can switch to a synthetic/proliferative phenotype. Here, we show that progerin expression in human and mouse VSMC causes a switch towards the synthetic phenotype. This switch elicits some level of replication stress in normal cells, which is exacerbated in the presence of progerin, leading to telomere fragility, genomic instability, and ultimately VSMC death. Calcitriol prevents replication stress, telomere fragility, and genomic instability, reducing VSMC death. In addition, RNA-seq analysis shows induction of a profibrotic and pro-inflammatory aging–associated secretory phenotype upon progerin expression in human primary VSMC. Our data suggest that phenotypic switch-induced replication stress might be an underlying cause of VSMC loss in progeria, which together with loss of contractile features and gain of profibrotic and pro-inflammatory signatures contribute to vascular stiffness in HGPS.

Elastin is a long-lived extracellular matrix protein that is organized into elastic fibers that provide elasticity to the arterial wall, allowing stretch and recoil with each cardiac cycle. By forming lamellar units with smooth muscle cells, elastic fibers transduce tissue-level mechanics to cell-level changes through mechanobiological signaling. Altered amounts or assembly of elastic fibers leads to changes in arterial structure and mechanical behavior that compromise cardiovascular function. In particular, genetic mutations in the elastin gene ( ELN) that reduce elastin protein levels are associated with focal arterial stenosis, or narrowing of the arterial lumen, such as that seen in supravalvular aortic stenosis and Williams–Beuren syndrome. Global reduction of Eln levels in mice allows investigation of the tissue- and cell-level arterial mechanical changes and associated alterations in smooth muscle cell phenotype that may contribute to stenosis formation. A loxP-floxed Eln allele in mice highlights cell type- and developmental origin-specific mechanobiological effects of reduced elastin amounts. Eln production is required in distinct cell types for elastic layer formation in different parts of the mouse vasculature. Eln deletion in smooth muscle cells from different developmental origins in the ascending aorta leads to characteristic patterns of vascular stenosis and neointima. Dissecting the mechanobiological signaling associated with local Eln depletion and subsequent smooth muscle cell response may help develop new therapeutic interventions for elastin-related diseases.

Dandelion (Taraxacum species) is a wild plant with over 2500 species. Flavonoids, phenolic compounds, saponins, sesquiterpenes, and sugars have been detected in the organs of Taraxacum, and for centuries it has been used in traditional medicine for the relief and treatment of various diseases. However, details of its working mechanism remain unclear. Bioactive compounds in herbal extracts generally have low yields, which makes their isolation and purification intensive in terms of time and cost. Here, to assess their versatility and safety, we applied aqueous extracts of two species of Taraxacum, T. mongolicum and T. formosanum, including extracts of both fresh and dried T. formosanum, to compare their potential antitumor effects on HeLa human cervical cancer cells, three liver cancer cell lines, and one normal liver cell line. After being treated with a lower dose of Taraxacum, the upregulation of subG1 and S populations, as well as increased levels of p-eIF2[Formula: see text]-to-eIF2[Formula: see text] ratio, were observed in HeLa cells, whereas the downregulation of S population and the absence of mRNA expressions were detected in HeLa cells when being treated with a higher dose of Taraxacum. These results indicated that Taraxacumcould induce apoptosis and endoplasmic reticulum stress while suppressing proliferation, transcription, colony formation, migration, and invasion. What’s more, we also found that the effects of fresh T. formosanum were much stronger than that of T. mongolicumin HeLa cells. Based on these results, we suggest that T. formosanum may contain specific compound(s) that are potentially useful for cancer therapy. However, much work remains to identify these effective compounds for the future application of Taraxacumto cancer therapy.

Breast cancer is a highly heterogeneous disease that has been clinically divided into three main subtypes: estrogen receptor (ER)- and progesterone receptor (PR)-positive, human epidermal growth factor receptor 2 (HER 2)-positive, and triple-negative breast cancer (TNBC). With its high metastatic potential and resistance to endocrine therapy, HER 2-targeted therapy, and chemotherapy, TNBC represents an enormous clinical challenge. The genus

In the resistance artery endothelium, we show phosphatidylserine (PS) localizes to a specific subpopulation of myoendothelial junctions (MEJs), signaling microdomains that regulate vasodilation. In silico data has implied PS may compete with PIP2 binding on Kir2.1, a channel involved in vasodilatory signaling. We found 83.33% of Kir2.1-MEJs also contained PS, possibly indicating an interaction where PS regulates Kir2.1. Electrophysiology experiments on HEK cells demonstrate PS blocks PIP2 activation of Kir2.1, and addition of exogenous PS blocks PIP2-mediated Kir2.1 vasodilation in resistance arteries. Using a mouse model lacking canonical MEJs in resistance arteries (Elnfl/fl/Cdh5-Cre), PS localization in endothelium was disrupted and PIP2 activation of Kir2.1 was significantly increased. Taken together, our data suggests PS enrichment to MEJs inhibits PIP2-mediated activation of Kir2.1 to tightly regulate changes in arterial diameter, and demonstrates the intracellular lipid localization within endothelium is an important determinant of vascular function.

The incineration of municipal solid waste has been important in waste management, but it raises another environmental issue concerning residue treatment. This study describes an innovative use of naturally aged incineration bottom ash (AIBA) as an alternative substrate for horizontal subsurface flow (HSSF) constructed wetlands (CW). Although experimental results from a period lasting for 396 days only revealed slightly higher removal ratios in HSSF with AIBA (HSSF-E) than in HSSF-traditional pebble beds (HSSF-C), increasing from 67% to 76% for BOD, 44%-51% for TKN, 47%-54% for NH

Hutchinson Gilford Progeria Syndrome is a premature aging disease caused by LMNA gene mutation and the production of a truncated lamin A protein “progerin” that elicits cellular and organismal toxicity. Progerin accumulates in the vasculature, being especially toxic for vascular smooth muscle cells (VSMC). Patients’ autopsies show that vessel stiffening, and aortic atherosclerosis is accompanied by VSMC depletion in the medial layer, altered extracellular matrix (ECM), and thickening of the adventitial layer. Mechanisms whereby progerin causes massive VSMC loss and vessel alterations remain poorly understood. Mature VSMC retain phenotypic plasticity and can switch to a synthetic/proliferative phenotype. Here we show that progerin expression in human and mouse VSMC causes a switch towards the synthetic/proliferative phenotype. This switch elicits some level of replication stress in normal cells, which is exacerbated in the presence of progerin, leading to telomere fragility, genomic instability, and ultimately VSMC death. Importantly, calcitriol prevents replication stress, telomere fragility, and genomic instability, reducing VSMC death. In addition, RNAseq analysis shows induction of a profibrotic and proinflammatory aging-associated secretory phenotype upon progerin expression in human primary VSMC. Our data suggest that phenotypic switch-induced replication stress might be an underlying cause of VSMC loss in progeria, which together with loss of contractile features and gain of profibrotic and proinflammatory signatures contribute to vascular stiffness in HGPS. Preventing the phenotypic switch-induced replication stress with compounds such as calcitriol might ameliorate CVD in HGPS patients.

Dandelion (

From the anti-inflammatory screening of Formosan Lauraceous plants, the methanolic extract of the root of Machilus zuihoensis var. mushaensis stood out for its potent inhibitory activity toward superoxide anion and elastase release in human neutrophils. Bioassay-guided fractionation of the root of M. zuihoensis var. mushaensis led to eight new compounds, including two butanolides (1-2), five lignanoids (3-7), and one sesquiterpenoid (8), along with 50 known compounds (9-58). Structures of these compounds were elucidated by NMR, UV, IR, CD, and MS analyses. Thirty-two isolates were evaluated for their anti-inflammatory activity. Among them, 9, 20, 27, 28, 30, 31, 35, and 40 exhibited significant superoxide anion generation inhibition selectively (ICsub50/subvalue lt; 7.4 μM), 15 and 19 showed selective inhibition toward elastase release (ICsub50/subvalue lt; 8.0 μM). Moreover, 3, 16, 21, and 22 simultaneously displayed superoxide anion generation and elastase release inhibition. It is worth mentioning that 21 and 22 showed more potent inhibitory activities (ICsub50/sub lt; 1.0 μM) on superoxide anion than the positive control, LY294002. Further quantitative HPLC analysis indicated the content of 21 and 22 were 0.90 and 3.04 mg/g (w/w) in the ethyl-acetate layer of the root of M. zuihoensis var. mushaensis, respectively. Altogether, M. zuihoensis var. mushaensis revealed a potential for developing the botanical new drug against inflammation-related disease.

Short bowel syndrome (SBS) is a particularly serious condition in which the small intestine does not absorb sufficient nutrients for biological needs, resulting in severe illness and potentially death if not treated. Given the important role of the gut in many signaling cascades throughout the body, SBS results in disruption of many pathways and imbalances in various hormones. Due to the inability to meet sufficient nutritional needs, an intravenous form of nutrition, total parental nutrition (TPN), is administered. However, TPN presents difficulties such as severe liver injury and altered signaling secondary to the continued lack of luminal contents. This manuscript aims to summarize relevant studies into the systemic effects of TPN on systems such as the gut–brain, gut-lung, and gut-liver axis, as well as present novel therapeutics currently under use or investigation as mitigation strategies for TPN induced injury.

Objective: Using a mouse model of Eln (elastin) insufficiency that spontaneously develops neointima in the ascending aorta, we sought to understand the origin and phenotypic heterogeneity of smooth muscle cells (SMCs) contributing to intimal hyperplasia. We were also interested in exploring how vascular cells adapt to the absence of Eln. Approach and Results: We used single-cell sequencing together with lineage-specific cell labeling to identify neointimal cell populations in a noninjury, genetic model of neointimal formation. Inactivating Eln production in vascular SMCs results in rapid intimal hyperplasia around breaks in the ascending aorta’s internal elastic lamina. Using lineage-specific Cre drivers to both lineage mark and inactivate Eln expression in the secondary heart field and neural crest aortic SMCs, we found that cells with a secondary heart field lineage are significant contributors to neointima formation. We also identified a small population of secondary heart field-derived SMCs underneath and adjacent to the internal elastic lamina. Within the neointima of SMC-Eln knockout mice, 2 unique SMC populations were identified that are transcriptionally different from other SMCs. While these cells had a distinct gene signature, they expressed several genes identified in other studies of neointimal lesions, suggesting that some mechanisms underlying neointima formation in Eln insufficiency are shared with adult vessel injury models. Conclusions: These results highlight the unique developmental origin and transcriptional signature of cells contributing to neointima in the ascending aorta. Our findings also show that the absence of Eln, or changes in elastic fiber integrity, influences the SMC biological niche in ways that lead to altered cell phenotypes.

Viral- and host-targeted traditional Chinese medicine (TCM) formulae NRICM101 and NRICM102 were administered to hospitalized patients with COVID-19 during the mid-2021 outbreak in Taiwan. We report the outcomes by measuring the risks of intubation or admission to intensive care unit (ICU) for patients requiring no oxygen support, and death for those requiring oxygen therapy.This multicenter retrospective study retrieved data of 840 patients admitted to 9 hospitals between May 1 and July 26, 2021. After propensity score matching, 302 patients (151 received NRICM101 and 151 did not) and 246 patients (123 received NRICM102 and 123 did not) were included in the analysis to assess relative risks.During the 30-day observation period, no endpoint occurred in the patients receiving NRICM101 plus usual care while 14 (9.27%) in the group receiving only usual care were intubated or admitted to ICU. The numbers of deceased patients were 7 (5.69%) in the group receiving NRICM102 plus usual care and 27 (21.95%) in the usual care group. No patients receiving NRICM101 transitioned to a more severe status; NRICM102 users were 74.07% less likely to die than non-users (relative risk= 25.93%, 95% confidence interval 11.73%-57.29%).NRICM101 and NRICM102 were significantly associated with a lower risk of intubation/ICU admission or death among patients with mild-to-severe COVID-19. This study provides real-world evidence of adopting broad-spectrum oral therapeutics and shortening the gap between outbreak and effective response. It offers a new vision in our preparation for future pandemics.

Background Diabetic patients are at high risk of developing cancer. Traditional Chinese medicine (TCM) has become increasingly popular as an adjuvant treatment for patients with chronic diseases, and some studies have identified its beneficial effect in diabetic patients with cancer. The purpoes of this study was to outline the potential of TCM to attenuate hospitalization and mortality rates in diabetic patients with carcinoma in situ (CIS). Methods A total of 6,987 diabetic subjects with CIS under TCM therapy were selected from the National Health Insurance Research Database of Taiwan, along with 38,800 of 1:1 sex-, age-, and index year-matched controls without TCM therapy. Cox proportional hazard analysis was conducted to compare hospitalization and mortality rates during an average of 15 years of follow-up. Results A total of 3,999/1,393 enrolled-subjects (28.62%/9.97%) had hospitalization/mortality, including 1,777/661 in the TCM group (25.43%/9.46%) and 2,222/732 in the control group (31.80%/10.48%). Cox proportional hazard regression analysis showed a lower rate of hospitalization and mortality for subjects in the TCM group (adjusted HR=0.536; 95% CI=0.367–0.780, P

Smooth muscle cells (SMCs) are specialized cells present in many organs where they serve diverse tissue-specific functions. Using the Tabula Muris compendium of single-cell RNA sequencing data, we extracted individual SMC transcriptomes from eight mouse tissues to investigate the transcriptomic landscape of tissue-specific SMCs. We identified marker genes, signaling pathways, and biological processes enriched in tissue-specific SMCs, and inferred potential ligand-receptor interaction between SMC and other cell types. Our analysis also identified sex differences in SMC gene expression in different tissues. Lastly, we used unsupervised clustering to identify novel SMC subtypes based on their downstream targets of transcription factors. Our results highlight the variable SMC phenotypes and underscore this cell’s remarkable adaptability to contribute to diverse tissue function.

Background: Diabetic patients are at high risk of developing cancer. Traditional Chinese medicine (TCM) has become increasingly popular as an adjuvant treatment for patients with chronic diseases, and some studies have identified its beneficial effect in diabetic patients with cancer. The purpoes of this study was to outline the potential of TCM to attenuate hospitalization and mortality rates in diabetic patients with carcinoma in situ (CIS). Methods: A total of 6,987 diabetic subjects with CIS under TCM therapy were selected from the National Health Insurance Research Database of Taiwan, along with 38,800 of 1:1 sex-, age-, and index year-matched controls without TCM therapy. Cox proportional hazard analysis was conducted to compare hospitalization and mortality rates during an average of 15 years of follow-up. Results: A total of 3,999/1,393 enrolled-subjects (28.62%/9.97%) had hospitalization/mortality, including 1,777/661 in the TCM group (25.43%/9.46%) and 2,222/732 in the control group (31.80%/10.48%). Cox proportional hazard regression analysis showed a lower rate of hospitalization and mortality for subjects in the TCM group (adjusted HR=0.536; 95% CI=0.367–0.780, P

Background We investigated the diversity and behaviour of insects that visit flowers of four native Melastoma (Family Melastomataceae ) species of Taiwan and a horticultural hybrid Melastoma species at the Fushan Botanical Garden, Taiwan biweekly from May to August 2020. Visits of flower-visiting insects were classified into seven behavioural categories, based on the insects' behaviour and positions on the flower. The data are further assigned into four insect-flower interactions, namely pollination, herbivory, commensalism and neutralism. Our goal is to provide baseline data of insect-plant interactions of Melastoma , which is a common, but understudied plant genus in the country. New information A total of 1,289 visits to flowers were recorded by at least 63 insect morphospecies belonging to seven orders. The number of insect species recorded per Melastoma species ranged from 9 to 39. Visiting, sonication and passing were the three most frequently recorded types of behaviour, collectively accounting for 90.2% (n = 1,240) of the total observations. Pollination was the most dominant insect-flower interaction, accounting for 70.2% of the total observations, followed by neutralism (20.0%), herbivory (6.3%) and commensalism (3.5%). Sweat bees of the genera Lasioglossum and Maculonomia ( Hymenoptera : Halictidae ) are considered key pollinators to Melastoma species in Fushan Botanical Garden, based on their high number of visits and sonication behaviour. Our study provides the first list of insects that visit the flowers of all Taiwan's known Melastoma species and description of their interactions with the plants.

Graphical abstract, Highlights • A herb-based formula delivers positive clinical outcomes on COVID-19 patients. • The formula inhibits SARS-CoV-2 pathogenesis in anti-viral & -inflammatory assays. • Real-world-evidence offers insights to inform drug development. • Bed-to-bench approach shortens the time required for finding effective therapeutics., COVID-19 is a global pandemic, with over 50 million confirmed cases and 1.2 million deaths as of November 11, 2020. No therapies or vaccines so far are recommended to treat or prevent the new coronavirus. A novel traditional Chinese medicine formula, Taiwan Chingguan Yihau (NRICM101), has been administered to patients with COVID-19 in Taiwan since April 2020. Its clinical outcomes and pharmacology have been evaluated. Among 33 patients with confirmed COVID-19 admitted in two medical centers, those (n = 12) who were older, sicker, with more co-existing conditions and showing no improvement after 21 days of hospitalization were given NRICM101. They achieved 3 consecutive negative results within a median of 9 days and reported no adverse events. Pharmacological assays demonstrated the effects of the formula in inhibiting the spike protein/ACE2 interaction, 3CL protease activity, viral plaque formation, and production of cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α. This bedside-to-bench study suggests that NRICM101 may disrupt disease progression through its antiviral and anti-inflammatory properties, offering promise as a multi-target agent for the prevention and treatment of COVID-19.

Graphical abstract

Background We investigated the diversity and behaviour of insects that visit flowers of four native Melastoma (Family Melastomataceae) species of Taiwan and a horticultural hybrid Melastoma species at the Fushan Botanical Garden, Taiwan biweekly from May to August 2020. Visits of flower-visiting insects were classified into seven behavioural categories, based on the insects' behaviour and positions on the flower. The data are further assigned into four insect-flower interactions, namely pollination, herbivory, commensalism and neutralism. Our goal is to provide baseline data of insect-plant interactions of Melastoma, which is a common, but understudied plant genus in the country. New information A total of 1,289 visits to flowers were recorded by at least 63 insect morphospecies belonging to seven orders. The number of insect species recorded per Melastoma species ranged from 9 to 39. Visiting, sonication and passing were the three most frequently recorded types of behaviour, collectively accounting for 90.2% (n = 1,240) of the total observations. Pollination was the most dominant insect-flower interaction, accounting for 70.2% of the total observations, followed by neutralism (20.0%), herbivory (6.3%) and commensalism (3.5%). Sweat bees of the genera Lasioglossum and Maculonomia (Hymenoptera: Halictidae) are considered key pollinators to Melastoma species in Fushan Botanical Garden, based on their high number of visits and sonication behaviour. Our study provides the first list of insects that visit the flowers of all Taiwan's known Melastoma species and description of their interactions with the plants.

Aortic aneurysms are morbid conditions that can lead to rupture or dissection and are categorized as thoracic (TAA) or abdominal aortic aneurysms (AAA) depending on their location. While AAA shares overlapping risk factors with atherosclerotic cardiovascular disease, TAA exhibits strong heritability. Human genetic studies in the past two decades have successfully identified numerous genes involved in both familial and sporadic forms of aortic aneurysm. In this review we will discuss the genetic basis of aortic aneurysm, focusing on the extracellular matrix and how insights from these studies have informed our understanding of human biology and disease pathogenesis.

Background Adults with congenital heart disease (ACHD) have traditionally been viewed as an underinsured population. Whether this is true in the Affordable Care Act era is unknown. We determined insurance patterns in ACHD patients compared to the non-ACHD cardiology population in a contemporary cohort. Methods All cardiology outpatient visits between July 2016 and February 2017 to a large referral center in the United States were reviewed. The primary payer was categorized as health maintenance organization (HMO), preferred provider organization (PPO), Medicare, Medicaid, self-pay, or other. Diagnosis and lesion severity of ACHD were extracted from ICD-10 diagnostic codes and assigned according to the 2008 American College of Cardiology/American Heart Association ACHD guidelines. Age-matching was used to account for baseline age differences between ACHD and non-ACHD patients. Results E ACHD and 17 154 non-ACHD patients were identified. Without age-matching, ACHD patients were significantly younger than non-ACHD patients (mean age 38.5 vs 63.8 years). After age-matching (N = 805 in each group), mean age was 39.5 years in both groups. ACHD patients had less HMO (29.1% vs 34.7%, P = .012) and Medicaid (12.4% vs 17.3%, P = .006) coverage, but more PPO (34.4% vs 27.5%, P = .003) and Medicare (23.2% vs 18.1%, P = .005) coverage compared to non-ACHD patients. No differences were found in private insurance, public insurance, or self-pay. Lesion complexity had no effect on insurance in ACHD patients. Eligibility of parental plan coverage did not affect use of private insurance. ACHD patients in states with Medicaid expansion had higher rates of Medicaid (15.6% vs 10.6%, P = .045) but lower rates of HMO coverage (24.5% vs 31.7%, P = .036) and self-pay (0% vs 3.3%, P

To investigate the impact of salinity on the pollution removal performance of constructed wetlands (CWs), four sets of hybrid CWs (HCW) were considered herein. The HCWs were composed of free water surface flow (FWS) and subsurface flow (SSF) CWs that were planted with cattail (Typha orientalis Presl.) and reed (Phragmites communis Trin.), respectively. After a preliminary experiment of almost seven months with influent fresh wastewater, NaCl was added at concentrations of 5 ppt, 10 ppt, and 20 ppt to simulate the impact of salinity. The removal performance was compared with that of the control CWs, and the impact of salinity on FWS CWs, SSF CWs, and HCWs were investigated. According to the experimental results, the biochemical oxygen demand (BOD) removal ratio in FWS CWs decreased from 70.3% to 58.3% as salinity increased from 0 ppt to 20 ppt, while that in SSF CWs fell significantly from 53.5% to 36.9% as salinity increased to ≧10 ppt. However, hybrid CWs offered more stable BOD removal and ammonia-nitrogen (NH3-N) removal under salinity impact. Salinity≧10 ppt stimulated the removal performance of NH3-N in FWS CWs to 19.4% while salinity≦5 ppt had no significant effect. In SSF CWs, a linear relationship was observed between removal loading and salinity, and NH3-N removal completely ceased at a salinity of 30.6 ppt. All removal ratios of NO3─-N>94.9% in FWS CWs revealed that salinity had almost no impact because the environment was anaerobic and contained sufficient organic carbon. The TP removal ratio in FWS CWs decreased from 14.7% to 9.2% as salinity increased from 0 ppt to 20 ppt and that in SSF CWs decreased monotonically from 7.2% to −0.2%. The impact period of salinity showed versatile reaction patterns of pollution removals in FWS CWs, SSF CWs, and HCWs. It distributed from 28 days to 186 days, after which the removal performance of CWs was restored.

BACKGROUND The use of posttransplant cyclophosphamide (PT-Cy) has contributed significantly to the success of haploidentical hematopoietic cell transplantation (HCT). Furthermore, several studies have shown promising results in the human leukocyte antigen–matched setting. However, the use of high-dose cyclophosphamide has been associated with the development of cardiomyopathy. There is a paucity of data concerning posttransplant cardiac complications in patients undergoing PT-Cy–based HCT. METHODS A retrospective analysis of 176 patients undergoing HCT with PT-Cy was performed. The overall survival, left ventricular ejection fractions, brain natriuretic peptide levels, and cardiac comorbidities were reviewed. The associations between comorbidities and the onset of heart failure were assessed with a Cox proportional hazards model. RESULTS Pretransplant cardiomyopathy was found in 16 patients (9.1%) but had no effect on their posttransplant overall survival. Thirty-five patients (21.9%) developed posttransplant cardiomyopathy, which correlated with increased mortality, but this was not statistically different from the frequency-matched non–PT-Cy cohort. The majority of these cardiomyopathies occurred in the setting of an infectious milieu. An age greater than 60 years and an HCT comorbidity index score equal to or greater than 4 were the only risk factors that correlated with posttransplant cardiomyopathy. CONCLUSIONS The presence of pretransplant cardiomyopathy does not negatively affect overall survival for patients who undergo HCT with PT-Cy. Furthermore, cardiomyopathy in PT-Cy patients is not caused by PT-Cy but is mostly concurrent with infectious complications and is associated with reduced overall survival. Traditional cardiovascular risk factors do not fully predict the occurrence of posttransplant cardiomyopathy. Future research is required to unravel predictive factors for cardiomyopathy after PT-Cy–based HCT. Cancer 2017;123:1800–1809. © 2017 American Cancer Society.

Rationale: Elastin is an important ECM (extracellular matrix) protein in large and small arteries. Vascular smooth muscle cells (SMCs) produce the layered elastic laminae found in elastic arteries but synthesize little elastin in muscular arteries. However, muscular arteries have a well-defined internal elastic lamina (IEL) that separates endothelial cells (ECs) from SMCs. The extent to which ECs contribute elastin to the IEL is unknown. Objective: To use targeted elastin (Eln) deletion in mice to explore the relative contributions of SMCs and ECs to elastic laminae formation in different arteries. Methods and Results: We used SMC- and EC-specific Cre recombinase transgenes with a novel floxed Eln allele to focus gene inactivation in mice. Inactivation of Eln in SMCs using Sm22aCre resulted in depletion of elastic laminae in the arterial wall with the exception of the IEL and SMC clusters in the outer media near the adventitia. Inactivation of elastin in ECs using Tie2Cre or Cdh5Cre resulted in normal medial elastin and a typical IEL in elastic arteries. In contrast, the IEL was absent or severely disrupted in muscular arteries. Interruptions in the IEL resulted in neointimal formation in the ascending aorta but not in muscular arteries. Conclusions: Combined with lineage-specific fate mapping systems, our knockout results document an unexpected heterogeneity in vascular cells that produce the elastic laminae. SMCs and ECs can independently form an IEL in most elastic arteries, whereas ECs are the major source of elastin for the IEL in muscular and resistance arteries. Neointimal formation at IEL disruptions in the ascending aorta confirms that the IEL is a critical physical barrier between SMCs and ECs in the large elastic arteries. Our studies provide new information about how SMCs and ECs contribute elastin to the arterial wall and how local elastic laminae defects may contribute to cardiovascular disease.

Implementing artificial intelligence (AI) for heating, ventilation and air conditioning (HVAC) energy-saving control requires complex pre-work or considerable training data, which are obstacles to practical application. This study developed smart-valve-assisted model-free predictive control to solve this application problem. Based on reinforce learning, model-free predictive control is recommended for situations in which no data can be provided for learning. To go further, smart valve hardware was used in the chiller plant to perform trial-and-error control of each air-conditioned space. By using smart valves, which can predict flow rates and exert control, control system can regulate and control lower stream for fan coils or air handling units in the chiller plant. The smart valves also record starting parameters to be used in later trial-and-error control and are key hardware for executing the model-free concept. This control engaged in interactive communication through the agent control program developed in this study. The overall control system is referred to simply as SV-MFPC. Energy-saving performances of SV-MFPC were tested in three different kinds of buildings include a hospital with a variable cooling load, an office building with a stable cooling load and a factory with a 24-hour operation load. The energy-saving effect was approximately 30% across these test sites. More important, the pre-work is simple, and the data required are only a thousandth of that required by other artificial intelligence technologies. This overcomes the technology gap and is the key to practical application.

Not all patients with angina pectoris have coronary artery stenosis. To facilitate the diagnosis of coronary artery disease (CAD), we sought to identify predictive factors of pulse spectrum analysis, which was developed by Wang and is one technique of modern pulse diagnosis. The patients suffered from chest pain and received cardiac catheterization to confirm the CAD diagnosis and Gensini score were recruited. Their pulse waves of radial artery were recorded. Then, by performing a fast Fourier transform, 10 amplitude values of frequency spectrum harmonics were obtained. Each harmonic amplitude was divided by the sum of all harmonic amplitude values, obtaining the relative percentages of 10 harmonics (C1-C10). Subsequently, multivariate logistic regression was conducted with two models and the areas under the receiver operating characteristic curves (ROC) of these 2 models were compared to see if combining the pulse diagnosis parameters with the risk factor of CAD can increase the prediction rate of CAD diagnosis. The predictive factors of CAD severity were analyzed by multivariate linear regression. A total of 83 participants were included; 63 were diagnosed CAD and 20 without CAD. In the CAD group, C1 was greater and C5 was lower than those of the non-CAD group. The CAD risk factors were put alone in Model 1 to perform the multivariate logistic regression analysis which had a prediction rate of 77.1%; while putting the C1 and C5 harmonics together with the risk factors into Model 2, the prediction rate increased to 80.7%. Finally, the area under ROC of Model 1 and Model 2 was 0.788 and 0.856, respectively. Furthermore, left C1, left C5, gender, and presence of hyperlipidemia were predictors of CAD severity. Therefore, pulse spectrum analysis may be a tool to facilitate CAD diagnosis before receiving cardiac catheterization. The harmonics C1 and C5 were favorable predictive indicators.

Background. Identifying patients with high risk of coronary artery disease (CAD) is often difficult in outpatient clinic settings. This study aimed to explore if the measurement of body constitution can be adopted to predict the risk of CAD diagnosis. The objective of this study is to conduct a prospective observational study and a case-control study to answer the research question. Study Design. Part 1 (prospective observational study): a total of 143 patients with chest pain and admitted to receive cardiac catheterization were enrolled, and 108 of them were diagnosed with CAD. Part 2 (case-control study): the above 108 CAD patients and 476 healthy controls matched by age and gender from the participants of Taiwan Biobank were adopted for comparison. Main Outcome Measures. The body constitution of both patients and healthy controls were measured by the Body Constitution Questionnaire (BCQ). Each one received scores of Yang-Xu (Yang-deficiency), Yin-Xu (Yin-deficiency), and Stasis. These 3 scores together with demographic characteristics and CAD risk factors were used in the logistic multiple regression model to predict the risk of CAD. Results. (Part 1) No difference was found between the scores of Yang-Xu, Yin-Xu, and Stasis between the patients with and without CAD. (Part 2) The scores of Yang-Xu, Yin-Xu, and Stasis of the CAD patients were significant higher those of the healthy controls. Yang-Xu and Stasis scores were obtained with age, BMI, and hypertension in the model with prediction rate 89.0%. The area under receiver operating characteristic curve of this model was 0.896. Conclusions. This study is the first to apply Chinese body constitution concepts and measurable variables to assess the risk of having CAD of the patients with chest pain prior to receiving cardiac catheterization. The higher scores of Yang-Xu and Stasis were found to be risk factors. Our results revealed that BCQ has the potential to be a first-line diagnostic tool for patients with chest pain to facilitate early recognition and diagnosis of CAD.

Left ventricular assist device (LVAD) has been increasingly utilized in the past decade for patients with end stage heart failure. The clinical course of acute myocardial infarction (AMI) after LVAD remains unclear. LVAD provides complete hemodynamic support irrespective of cardiac rhythm or

The pollutant removal performance of traditional horizontal subsurface flow (HSSF) constructed wetlands (CWs) is limited because of the dissolved oxygen (DO) supply is insufficient. The aeration of HSSF CWs usually improves their pollutant removal performance, but a high DO induces the accumulation of nitrate-nitrogen (NO3−-N) and suppresses the improvement of total nitrogen (TN) removal. In this study, an integrated solution that involved in-tank front aeration and internal recirculation (FAIR) was used to improve the pollutant removal performance of HSSF CWs. Based on the experimental results, the FAIR system significantly increased the removal efficiencies of biochemical oxygen demand (BOD) from 53.8–76.0% to 82.0–91.7% and reduced the BOD concentration in the effluent to below 10 mg L−1. The removal efficiency of ammonia-nitrogen (NH3–N) increased from 15.1–78.3% to 98.5–98.6% while the removal efficiencies of the total Kjeldahl nitrogen (TKN) of the control and FAIR HSSF CWs were 18.2–77.1% and 93.5–94.3%, respectively. HSSF CWs with FAIR outperformed aerated HSSF CWs in the removal of NH3–N and TKN. The effects of two recirculation flow ratios (Rr = recirculation flow rate/influent flow rate), 14.3 and 3.0, on the improvement of pollutant removal performance were investigated. The lower Rr did not significantly affect the improvement of BOD, NH3–N, and TKN, but a higher Rr resulted in more severe accumulation of NO3−-N. The removal efficiency of TN in control HSSF CWs ranged from 20.4% to 75.5%, and in the FAIR HSSF CW was 71.6% for Rr = 14.3 and 81.3% for Rr = 3.0. However, the FAIR system did not enhance the removal performance of total phosphorus, suggesting that the DO level and internal recirculation were not dominant mechanisms for the removal of phosphorous. The easy maintenance of the FAIR system made it a superior modification for improving the pollutant removal performance of HSSF CWs.

CHARGE syndrome is a multiple anomaly disorder in which patients present with a variety of phenotypes, including ocular coloboma, heart defects, choanal atresia, retarded growth and development, genitourinary hypoplasia and ear abnormalities. Despite 70-90% of CHARGE syndrome cases resulting from mutations in the gene CHD7, which encodes an ATP-dependent chromatin remodeller, the pathways underlying the diverse phenotypes remain poorly understood. Surprisingly, our studies of a knock-in mutant mouse strain that expresses a stabilized and transcriptionally dead variant of the tumour-suppressor protein p53 (p53(25,26,53,54)), along with a wild-type allele of p53 (also known as Trp53), revealed late-gestational embryonic lethality associated with a host of phenotypes that are characteristic of CHARGE syndrome, including coloboma, inner and outer ear malformations, heart outflow tract defects and craniofacial defects. We found that the p53(25,26,53,54) mutant protein stabilized and hyperactivated wild-type p53, which then inappropriately induced its target genes and triggered cell-cycle arrest or apoptosis during development. Importantly, these phenotypes were only observed with a wild-type p53 allele, as p53(25,26,53,54)(/-) embryos were fully viable. Furthermore, we found that CHD7 can bind to the p53 promoter, thereby negatively regulating p53 expression, and that CHD7 loss in mouse neural crest cells or samples from patients with CHARGE syndrome results in p53 activation. Strikingly, we found that p53 heterozygosity partially rescued the phenotypes in Chd7-null mouse embryos, demonstrating that p53 contributes to the phenotypes that result from CHD7 loss. Thus, inappropriate p53 activation during development can promote CHARGE phenotypes, supporting the idea that p53 has a critical role in developmental syndromes and providing important insight into the mechanisms underlying CHARGE syndrome.