Abstract
Objective. Patients with hypertensive left-ventricular hypertrophy (LVH) have lower coronary flow reserve (CFR). Whether carvedilol can improve CFR of patients with hypertensive LVH is ...unknown. We aimed to investigate the effects of carvedilol on CFR in patients with hypertensive LVH. Methods. Sixty-three patients were randomly divided into two groups for treatment with carvedilol or metoprolol. The peak diastolic coronary flow velocity in the left anterior descending coronary artery at rest and at maximal vasodilation with dipyridamole infusion was recorded by transesophageal echocardiography (TEE), then CFR was calculated at baseline and at the end of 6 months of therapy. Left-ventricular mass index (LVMI) was calculated by 2-D echocardiography. Endothelium-dependent and -independent reactivity of the brachial artery was measured. Levels of plasma endothelin-1 (ET1), nitric oxide (NO) and other metabolites were monitored and analyzed before and after 6-month therapy. Results. Both blood pressure and heart rate decreased significantly in the two treatment groups after therapy (p<0.05). With carvedilol treatment, LVMI was lower (p<0.05), endothelium function of the brachial artery was higher (p<0.05), and peak diastolic coronary flow velocity at rest and at maximal vasodilation after dipyridamole infusion was significantly higher (p<0.05) than with metoprolol treatment, which led to a significantly higher CFR (p<0.05). Changes in CFR and LVMI with carvedilol treatment were inversely correlated (R2=0.474, p=0.036). With carvedilol treatment, plasma level of ET-1 was lower, but that of NO was significantly higher than with metoprolol treatment (both p<0.05). Conclusions. The CFR of patients with hypertensive LVH but not coronary artery disease could increase with 6-month carvedilol therapy.
To push the commercialization of the promising photovoltaic technique of perovskite solar cells (PSCs), the three-element golden law of efficiency, stability, and cost should be followed. As the key ...component of PSCs, hole-transporting materials (HTMs) involving widely-used organic semiconductors such as 2,2',7,7'-tetrakis-(N,N-di-4-methoxyphenylamino)-9,9'-spirobifluorene (Spiro-OMeTAD) or poly(triarylamine) (PTAA) usually suffer high-cost preparation and low operational stability. Fortunately, the studies on the classical p-type polymer poly(3-hexylthiophene) (P3HT) as an alternative HTM have recently sparked a broad interest due to its low-cost synthesis, excellent batch-to-batch purity, superior hole conductivity as well as controllable and stable film morphology. Despite this, the device efficiency still lags behind P3HT-based PSCs mainly owing to the mismatched energy level and poor interfacial contact between P3HT and the perovskite layer. Hence, in this review, the study timely summarizes the developed strategies for overcoming the corresponding issues such as interface engineering, morphology regulation, and formation of composite HTMs from which some critical clues can be extracted to provide guidance for further boosting the efficiency and stability of P3HT-based devices. Finally, in the outlook, the future research directions either from the viewpoint of material design or device engineering are outlined.
Carbon quantum dots (CQDs), a new type of fluorescence carbon nanomaterials with particle size varied from 2 to 10 nm, have attracted much attention due to their strong multi-color luminescence ...properties, unprecedented biocompatibility, excellent aqueous dispersibility and easy preparation from a wide range of carbon materials. These multiple attributes help CQDs possess a broad range of prospective applications in numerous fields, especially for bio-imaging, drug delivery, chemical probe and photon therapy because of their advantages of low cytotoxicity and good biocompatibility. Therefore, it is necessary to recap the synthesis and application of CQDs-based materials in the field of biomedicine. The methods for the synthesis of CQDs are introduced firstly, and then different performance of CQDs related to their applications are demonstrated and discussed, including the function tailoring of CQDs. Finally, future opportunities and challenges of CQDs-based materials in this burgeoning field are proposed from the perspective of the rational design of systematic CQDs-based materials toward the biomedicine field.
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•CQDs acted as a fluorescent dye has emerged with great interest.•The performances of CQDs in cancer treatment are discussed systematically.•This review provides a practicable guidance for the design of advanced fluorescence CQDs.•Future perspectives and challenges in practical application are also investigated.
Poor adventitious root (AR) formation poses a major constraint to the propagation of tea cuttings. The present study identified two tea cultivars with different rooting behavior:
Camellia sinensis
...cv. Taixuan 0310 (TX), with strong and rapid rooting; and
C. sinensis
cv. Qianmei 601 (QM), with poor and slow rooting. To elucidate the molecular events underlying AR formation in tea cuttings, transcriptomic analysis was performed during early root formation and root elongation. Differentially expressed genes (DEGs) between TX and QM were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that phenylpropanoid biosynthesis, plant hormone signal transduction, plant MAPK signaling and plant-pathogen interaction, all play important roles in AR information in
C. sinensis
. Among the DEGs, two
GRETCHEN HAGEN3
(
GH3
) genes,
CsGH3.2
and
CsGH3.3
, were isolated and characterized. Quantitative real-time PCR (qRT-PCR) and molecular analysis suggest that
CsGH3
.
2
and
CsGH3
.
3
may have specific functions in different organs. Moreover, overexpression of
CsGH3.2
and
CsGH3.3
inhibited root growth and development in transgenic rice plant. These results give new insights into the possible role of
CsGH3.2
and
CsGH3.3
in adventitious rooting, and also provide an interesting starting point to discover new genes involved in AR formation in tea cuttings.
Key message
Transcriptomic analysis revealed the molecular events underlying adventitious root formation in tea cuttings, and facilitated the discovery of genes involved in this process.
CsGH3.2
and
CsGH3.3
appear to function in adventitious rooting in tea cuttings.
A two-in-one breeding strategy promotes rapid utilization of wild species and elite varieties. (a) Schematics illustrating the breeding strategy. (b) Phylogeny of tomato strictosidine synthase family ...proteins. (c) Expression atlas of SlLAP3. (d) The CRISPR construct for SlLAP3 and verified null mutation alleles. (e) Reciprocal crosses between AC and sllap3 confirming the male sterility. (f) Images showing reproductive organs of AC and sllap3 plants. (g) Alexander staining (left panel) and confocal imaging (right panel) showing pollen defects of sllap3 plants. (h–k) Images and quantitative data showing shoot architecture, fruits and seeds from self-pollinated AC, sllap3 and manual-pollinated sllap3 by AC pollens. (l) Representative images showing wild and de novo domesticated S. pimp with sp sp5g mutations. (m, n) Phenotypes and statistics of F1 progeny from cross between sllap3 and S. pimp sp sp5g. (o–p) Phenotypic comparison and quantification between parental plants and F2 progenies upon salt solution irrigation. (q) Representative plants, statistics and schematics showing F2 progenies segregated to fit three different cultivation modes. ...we selected wild species Solanum pimpinellifolium (S. pimp) as the introgression donor, an ancestor of modern tomato with excellent stress tolerance (Lin et al., 2014). ...we crossed de novo domesticated S. pimp lines with male-sterile AC plants.
•Mutation of OsRBAP1 at residue 65 leads to a dwarf phenotype in rice.•Switching off OsRBAP1 in rice leads to severe reductions in height and fertility.•Transcriptome analysis suggests that OsRBAP1 ...modulates essential genes involved in multiple pathways.
To explore the molecular mechanisms underlying plant height regulation, we isolated and characterized a stably inherited semi-dwarf mutant bgsd-2 from the ethane methyl sulfonate (EMS) mutant progeny of ‘Ping Tang Wild-type (PTWT)’, a rice (Oryza sativa ssp. japonica) landrace in Guizhou. Transcriptome sequencing and qRT-PCR analyses showed that a number of cellulose and lignin-related genes involved in cell wall biogenesis were substantially downregulated in bgsd-2. MutMap-based cloning revealed the occurrence of a single amino acid substitution in the LOC_Os01g51300 gene, belonging to the MSI1 (multicopy suppressor of IRA1) member OsRBAP1. The bgsd-2 mutation occurred in the 3rd exon of OsRBAP1, resulting in a nonsense mutation of a codon shift from glycine (G) to glutamic acid (E) at residue 65. Protein localization analysis uncovered that the OsRBAP1 gene encodes a nuclear-localized protein and that the mutation in bgsd-2 may affect the stability of the OsRBAP1 protein. The CRISPR/Cas9 system was used to switch off OsRBAP1 in PTWT to obtain the knockout mutant osrbap1, which exhibited a severe reduction in height and fertility. Cytological observations suggest that the dwarfism of osrabp1 may be caused by reduced cell size and numbers, and that male sterility may be due to abnormal microspore development. Transcriptome analysis revealed that OsRBAP1 defects can repress the expression of numerous essential genes, which regulate multiple developmental processes in plants. Altogether, our results suggest that OsRBAP1 plays an important role in the regulation of rice height and spikelet fertility.
Shear stress (SS) and renin-angiotensin system (RAS) play important roles in endothelium homeostasis. Previous studies demonstrated that pulsatile shear stress (PSS) reduced the expression and ...activity of angiotensin-converting enzyme (ACE), however, the effect of SS on angiotensin-converting enzyme 2 (ACE2) expression is unclear.
We exposed cultured endothelial cells (ECs) to distinct patterns of SS for indicated time points, Western blot and RT-PCR were used to determine the ACE2 expression; En Face staining was used to detect ACE2 expression in vivo; cell proliferation and apoptosis were determined by BrdU staining and TUNEL staining, respectively; the production of NO was detected by a commercial kit; the promoter activity of ACE2 was determined by a Dual-Luciferase Reporter Assay System, inhibitors of ACE2 and signaling pathway were added to the medium 1 h prior for PSS. Our data showed PSS induced a sustained ACE2 expression, but OSS only induced a transient ACE2 expression. The PSS-induced ACE2 expression was higher than that of OSS both in vitro and in vivo. The PSS-induced ACE2 was involved in inhibiting proliferation and inflammation, as well as promoting NO production in ECs. PSS significantly increased ACE2 expression at transcriptional level via activating AMPKα2-KLF2 pathway.
Our results suggest PSS promotes ACE2 expression via AMPKα2-KLF2 pathway to maintain the normal EC functions.
In the, we firstly demonstrated that• Pulsatile shear stress (PSS) increased the ACE2 expression• PSS- induced ACE2 was participated in promoting the NO production, reducing the proliferation and inflammation of sheared ECs.• The AMPK-KLF2 pathway was involved in the upregulation of ACE2 by PSS.This work will help us further understand the relationship between RAS and mechanical forces.
Abstract
The KMT2D variant–caused Kabuki syndrome (KS) is characterized by short stature as a prominent clinical characteristic. The initiation and progression of body growth are fundamentally ...influenced by chondrocyte proliferation. Uncertainty persists regarding the possibility that KMT2D deficiency affects growth by impairing chondrocyte proliferation. In this study, we used the CRISPR/Cas13d technique to knockdown kmt2d in zebrafish embryos and lentivirus to create a stable Kmt2d gene knockdown cell line in chondrocytes (ATDC5 cells). We also used CCK8 and flow cytometric studies, respectively, to determine proliferation and cell cycle state. The relative concentrations of phosphorylated Akt (ser473), phosphorylated β-catenin (ser552), and cyclin D1 proteins in chondrocytes and zebrafish embryos were determined by using western blots. In addition, Akt inhibition was used to rescue the phenotypes caused by kmt2d deficiency in chondrocytes, as well as a zebrafish model that was generated. The results showed that a knockdown of kmt2d significantly decreased body length and resulted in aberrant cartilage development in zebrafish embryos. Furthermore, the knockdown of Kmt2d in ATDC5 cells markedly increased proliferation and accelerated the G1/S transition. In addition, the knockdown of Kmt2d resulted in the activation of the Akt/β-catenin signaling pathway in ATDC5 cells. Finally, Akt inhibition could partly rescue body length and chondrocyte development in the zebrafish model. Our study demonstrated that KMT2D modulates bone growth conceivably via regulation of the Akt/β-catenin pathway.
Graphical Abstract
Graphical abstract
Nickel oxide is one of the most promising hole‐transporting materials in inverted perovskite solar cells (PSCs) but suffers from undesired reactions with perovskite which leads to limited device ...performance and stability. Self‐assembled monolayers (SAMs) are demonstrated to effectively optimize the NiOx/perovskite interface, but the significance of the compactness of the SAM at the interface is less investigated. Here, a series of methoxy‐substituted triphenylamine functionalized benzothiadiazole (TBT) based SAM molecules, TBT‐BA, TBT‐FBA, and TBT‐DBA, with benzoic acid, 2‐fluorobenzoic acid and isophthalic acids as anchoring groups are used to modify NiOx. TBT‐BA with the simplest structure is demonstrated to form the densest SAM on NiOx, thus optimized NiOx/SAM/perovskite interface is achieved with enhanced charge collection and suppressed interfacial reaction and recombination. TBT‐BA can also passivate the perovskite most effectively due to the highest binding energy toward perovskite, thus the corresponding inverted PSCs show the highest PCE of 24.8% and maintain 88.7% of the initial PCE after storage at 60 °C for 2635 h in the glovebox. The work provides important insights into designing SAM molecules for modification transporting layers for efficient and stable PSCs.
Self‐assembled monolayers (SAM) modified nickel oxide (NiOx) is used as a hole‐selective layer in inverted perovskite solar cells and finally, the highest power conversion efficiency of 24.8% is achieved with excellent thermal stability by the highest coverage of SAM on NiOx.
Mendelian disorders of the epigenetic machinery (MDEMs) are caused by genetic mutations, a considerable fraction of which are associated with epigenetic modification. These MDEMs exhibit phenotypic ...overlap broadly characterized by multiorgan abnormalities. The variant detected in genes associated with epigenetic modification can lead to short stature accompanied with multiple system abnormalities. This study is aimed at presenting and summarizing the diagnostic rate, clinical, and genetic profile of MDEMs-associated short stature. Two hundred and fourteen short-stature patients with multiorgan abnormalities were enrolled. Clinical information and whole exome sequence (WES) were analyzed for these patients. WES identified 33 pathogenic/likely pathogenic variants in 19 epigenetic modulation genes (
KMT2A
,
KMT2D
,
KDM6A
,
SETD5
,
KDM5C
,
HUWE1
,
UBE2A
,
NIPBL
,
SMC1A
,
RAD21
,
CREBBP
,
CUL4B
,
BPTF
,
ANKRD11
,
CHD7
,
SRCAP
,
CTCF
,
MECP2
,
UBE3A
) in 33 patients (15.4%). Of note, 19 variants had never been reported previously. Furthermore, these 33 variants were associated with 16 different disorders with overlapping clinical features characterized by development delay/intelligence disability (31/33; 93.9%), small hands (14/33; 42.4%), clinodactyly of the 5th finger (14/33; 42.4%), long eyelashes (13/33; 39.4%), and hearing impairment (9/33; 27.3%). Additionally, several associated phenotypes are reported for the first time: clubbing with
KMT2A
variant, webbed neck with
SETD5
variant, retinal detachment with
CREBBP
variant, sparse lateral eyebrow with
HUWE1
variant, and long palpebral fissure with eversion of the lateral third of the low eyelid with
SRCAP
variant.
Conclusions
: Our study provided a new conceptual framework for further understanding short stature. Specific clinical findings may indicate that a short-stature patient may have an epigenetic modified gene variant.
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