Integrated Transcriptome and Metabolome Analyses Reveal Bamboo Culm Color Formation Mechanisms Involved in Anthocyanin Biosynthetic in Phyllostachys nigra.

Phyllostachys nigra has green young culms (S1) and purple black mature culms (S4). Anthocyanins are the principal pigment responsible for color presentation in ornamental plants. We employ a multi-omics approach to investigate the regulatory mechanisms of anthocyanins in Ph. nigra. Firstly, we found that the pigments of the culm of Ph. nigra accumulated only in one to four layers of cells below the epidermis. The levels of total anthocyanins and total flavonoids gradually increased during the process of bamboo culm color formation. Metabolomics analysis indicated that the predominant pigment metabolites observed were petunidin 3-O-glucoside and malvidin O-hexoside, exhibiting a significant increase of up to 9.36-fold and 13.23-fold, respectively, during pigmentation of Ph. nigra culm. Transcriptomics sequencing has revealed that genes involved in flavonoid biosynthesis, phenylpropanoid biosynthesis, and starch and sucrose metabolism pathways were significantly enriched, leading to color formation. A total of 62 differentially expressed structural genes associated with anthocyanin synthesis were identified. Notably, PnANS2, PnUFGT2, PnCHI2, and PnCHS1 showed significant correlations with anthocyanin metabolites. Additionally, certain transcription factors such as PnMYB6 and PnMYB1 showed significant positive or negative correlations with anthocyanins. With the accumulation of sucrose, the expression of PnMYB6 is enhanced, which in turn triggers the expression of anthocyanin biosynthesis genes. Based on these findings, we propose that these key genes primarily regulate the anthocyanin synthesis pathway in the culm and contribute to the accumulation of anthocyanin, ultimately resulting in the purple-black coloration of Ph. nigra.

Bridging the gap: Public engagement in blue-green space development for healthier urban futures.

BACKGROUND: With the rapid escalation of global urbanization, the role of blue-green spaces in urban ecology, public health, and planning has become increasingly prominent. Although their contributions to ecological preservation, public health, and urban design are widely acknowledged, research into public engagement and willingness to participate in the management and planning of these spaces is still in its early stages. OBJECTIVE: This study aims to identify key factors influencing public willingness to participate in blue-green space management, focusing specifically on people's perceptions of blue-green spaces (including perceived quality and accessibility), their usage behaviors (i.e., frequency of usage of blue-green spaces), and their self-assessed physical and mental health. METHODS: We interviewed local residents through random sampling to obtain sample data, and used a representative sample (n = 815, 510 women; 305 men, age 18-85 years, lived in Chengdu for an extensive time) of residents living in Chengdu City, China. Employing a quantitative approach, we examined the relationships between factors such as gender, regular occupation, income, behavior, and health status in relation to the willingness to participate. Additionally, we explored how perceptions and behaviors impacted health statuses and, consequently, inclinations to participate. RESULTS: The findings indicate that individuals with steady occupations and higher incomes are more inclined to engage in the management and planning of blue-green spaces. Notably, men exhibited a greater tendency to participate than women. Furthermore, access to blue-green spaces emerged as a crucial mechanism for addressing health disparities, offering significant implications for urban planning and public health. CONCLUSION: Successful blue-green space planning and understanding of willingness to participate necessitates the holistic consideration of people's perceptions of blue-green spaces, their usage behaviour and their self-rate health. For a tangible impact on health equity and global urban development, it's essential to prioritize blue-green spaces in planning, especially in lower-income regions. This not only promotes environmental perception but can also be a strategic approach to address health disparities. Our findings offer vital insights for tailoring international urban planning and management practices towards these goals.

A personal narrative intervention combined with self-monitoring strategies: Outcomes for Mandarin-speaking adolescents with Down syndrome.

BACKGROUND: Personal narratives play an essential role in children's social and academic development. However, children with Down syndrome have ongoing challenges with constructing and communicating personal narratives. METHODS: Using a single-case multiple-probe across participants design, we examined whether a targeted intervention could improve both micro- and macro-structural aspects of personal narratives from Chinese adolescents with Down syndrome. RESULTS: All three participants demonstrated high treatment effects in two macrostructural narrative outcomes (i.e., narrative element complexity and narrative coherence) in response to the intervention and moderate to high treatment effects in the microstructural narrative outcomes (i.e., the mean length of utterance in words and the number of different words). However, all participants demonstrated limited improvements in narrative cohesion. These effects were maintained and generalised in a different narrative condition. CONCLUSIONS: The preliminary findings support the feasibility and effectiveness of the personal narrative intervention incorporated with self-monitoring strategies for adolescents with Down syndrome.

Quantum Implementation of the SAND Algorithm and Its Quantum Resource Estimation for Brute-Force Attack.

The SAND algorithm is a family of lightweight AND-RX block ciphers released by DCC in 2022. Our research focuses on assessing the security of SAND with a quantum computation model. This paper presents the first quantum implementation of SAND (including two versions of SAND, SAND-64 and SAND-128). Considering the depth-times-width metric, the quantum circuit implementation of the SAND algorithm demonstrates a relatively lower consumption of quantum resources than that of the quantum implementations of existing lightweight algorithms. A generalized Grover-based brute-force attack framework was implemented and employed to perform attacks on two versions of the SAND algorithm. This framework utilized the g-database algorithm, which considered different plaintext-ciphertext pairs in a unified manner, reducing quantum resource consumption. Our findings indicate that the SAND-128 algorithm achieved the NIST security level I, while the SAND-64 algorithm fell short of meeting the requirements of security level I.

Ino80 is required for H2A.Z eviction from hypha-specific promoters and hyphal development of Candida albicans.

ATP-dependent chromatin remodeling complexes play important roles in many essential cellular processes, including transcription regulation, DNA replication, and repair. Evicting H2A.Z, a variant of histone H2A, from the promoter of hypha-specific genes is required for hyphal formation in Candida albicans. However, the mechanism that regulates H2A.Z removal during hyphal formation remains unknown. In this study, we demonstrated that Ino80, the core catalytic subunit of the INO80 complex, was recruited to hypha-specific promoters during hyphal induction in Arp8 dependent manner and facilitated the removal of H2A.Z. Deleting INO80 or mutating the ATPase site of Ino80 impairs the expression of hypha-specific genes (HSGs) and hyphal development. In addition, we showed that Ino80 was essential for the virulence of C. albicans during systemic infections in mice. Interestingly, Arp5, an INO80 complex-specific component, acts in concert with Ino80 during DNA damage responses but is dispensable for hyphal induction. Our findings clarified that Ino80 was critical for hyphal development, DNA damage response, and pathogenesis in C. albicans.

Unravelling the genetic diversity and population structure of common walnut in the Iranian Plateau.

BACKGROUND: Common walnut (Juglans regia L.) has a long cultivation history, given its highly valuable wood and rich nutritious nuts. The Iranian Plateau has been considered as one of the last glaciation refugia and a centre of origin and domestication for the common walnut. However, a prerequisite to conserve or utilize the genetic resources of J. regia in the plateau is a comprehensive evaluation of the genetic diversity that is conspicuously lacking. In this regard, we used 31 polymorphic simple sequence repeat (SSR) markers to delineate the genetic variation and population structure of 508 J. regia individuals among 27 populations from the Iranian Plateau. RESULTS: The SSR markers expressed a high level of genetic diversity (HO = 0.438, and HE = 0.437). Genetic differentiation among the populations was moderate (FST = 0.124), and genetic variation within the populations (79%) significantly surpassed among populations (21%). The gene flow (Nm = 1.840) may have remarkably influenced the population genetic structure of J. regia, which can be attributed to anthropological activities and wind dispersal of pollen. The STRUCTURE analysis divided the 27 populations into two main clusters. Comparing the neighbor-joining and principal coordinate analysis dendrograms and the Bayesian STRUCTURE analysis revealed the general agreement between the population subdivisions and the genetic relationships among the populations. However, a few geographically close populations dispersed into different clusters. Further, the low genetic diversity of the Sulaymaniyah (SMR) population of Iraq necessitates urgent conservation by propagation and seedling management or tissue culture methods; additionally, we recommend the indispensable preservation of the Gonabad (RGR) and Arak (AKR) populations in Iran. CONCLUSIONS: These results reflected consistent high geographical affinity of the accession across the plateau. Our findings suggest that gene flow is a driving factor influencing the genetic structure of J. regia populations, whereas ecological and geological variables did not act as strong barriers. Moreover, the data reported herein provide new insights into the population structure of J. regia germplasm, which will help conserve genetic resources for the future, hence improving walnut breeding programs' efficiency.

Functional and Morphological Brain Alterations in Dysthyroid Optic Neuropathy: A Combined Resting-State fMRI and Voxel-Based Morphometry Study.

BACKGROUND: Increasing evidence has indicated that the entire visual pathway from retina to visual cortex may be involved in dysthyroid optic neuropathy (DON) pathological mechanisms. PURPOSE: To explore the functional and morphological brain characteristics in DON and their relationship with ophthalmologic performance. STUDY TYPE: Retrospective. POPULATION: A total of 30 DON patients, 40 thyroid-associated ophthalmopathy (TAO) without DON patients and 21 healthy-controls (HCs). FIELD STRENGTH/SEQUENCE: A 3.0 T, 3D T1-weighted spoiled gradient-recalled echo and gradient-recalled echo-planar imaging. ASSESSMENT: Functional and structural alterations in brain regions were evaluated with fractional amplitude of low-frequency fluctuations, degree centrality (DC), and gray matter volume (GMV). Clinical activity score (CAS) is assessed across patients. STATISTICAL TEST: One-way analysis of variance with post hoc two sample t-tests (GRF-corrected, voxel level: P < 0.005, cluster level: P < 0.05) and correlation analysis (significance level: P < 0.05). RESULTS: Compared to HCs, DON patients had significantly decreased DC values in the bilateral BA17 and BA18 regions. Compared to the TAO group, DON patients had decreased GMV in the left anterior cingulate cortex, left middle frontal gyrus, left lingual gyrus, left parietal gyrus, right Rolandic operculum, left supplementary motor area, and right middle temporal gyrus. In addition, GMV in the right Rolandic operculum was significantly positively correlated with CAS (correlation coefficient: r = 0.448). DATA CONCLUSION: This study showed significant morphological and functional alterations in visual cortex and morphological alterations in partial default mode network regions of DON patients, which may provide insights into the mechanism of vision loss and may facilitate the diagnosis and treatment of DON. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 3.

Preliminary Diffusion-Tensor Imaging Evidence for Trans-Synaptic Axonal Degeneration in Dysthyroid Optic Neuropathy Due to Thyroid-Associated Ophthalmopathy.

BACKGROUND: The mechanism driving dysthyroid optic neuropathy (DON) is unclear. Diffusion-tensor imaging (DTI) allows for noninvasively assessing the microstructure of the entire visual pathway and may facilitate a better understanding of the mechanism of DON. PURPOSE: To assess microstructural changes of the whole visual pathway and to investigate the potential mechanism of trans-synaptic damage（TSD） pathogenesis in DON with DTI. STUDY TYPE: Cross-sectional. POPULATION: Sixty-four patients with bilateral thyroid-associated ophthalmopathy (TAO), 30 with and 34 without DON, and 30 age- and sex-matched healthy controls (HCs). FIELD STRENGTH/SEQUENCE: 3 T/DTI (A single-shot diffusion-weighted echo-planar imaging sequence). ASSESSMENT: Differences in DTI parameters including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in each segment (optic nerve, tract, and radiation) of the entire visual pathway among the groups were compared. The parameters of visual evoked potentials (VEPs), visual field tests, and mean retinal nerve fiber layer (mRNFL) thickness on optical coherence tomography were also compared across patients. STATISTICAL TESTS: Student's t-test, chi-square test; ANOVA with post-hoc testing, interclass correlation coefficient, and correlation analysis. Significance level: P < 0.05. RESULTS: TAO patients with DON showed significantly reduced mRNFL thickness and abnormal VEPs. There was a tendency for gradually reduced FA and AD, and increased RD and MD from HCs, with non-DON to with DON in optic nerve and tract, statistically. For radiation, the RD and MD showed statistical increase, the AD and FA just showed numerical decrease (P = 0.119 and 0.059, respectively). For DON, the FA and MD of visual pathway segments showed correlations with abnormal VEPs. DATA CONCLUSION: DTI may be a useful tool for detecting microstructural changes in the entire visual pathway in DON. The changes in RNFL thickness and DTI parameters suggested TSD as a potential pathogenic mechanism of DON. EVIDENCE LEVEL: 4 Technical Efficacy: Stage 5.

Aberrant spontaneous brain activity in patients with thyroid-associated ophthalmopathy with and without optic neuropathy: a resting-state functional MRI study.

OBJECTIVES: To investigate the brain functional alterations in dysthyroid optic neuropathy (DON) by evaluating spontaneous neural activity, using functional magnetic resonance imaging (fMRI) with regional homogeneity (ReHo), and its relationship with ophthalmologic performance. METHODS: Forty-seven patients with thyroid-associated ophthalmopathy (TAO; 20 with DON, 27 with non-DON) and 33 age-, sex-, and education-matched healthy controls (HCs) underwent fMRI. ReHo values were compared using one-way analysis of variance (ANOVA) with post hoc pairwise comparisons (voxel-level p < 0.01, Gaussian random field correction, cluster-level p < 0.05). Correlations between ReHo values and ophthalmological metrics were assessed for DONs, with Bonferroni correction for multiple comparisons (p < 0.004). ROC curves were applied to evaluate the diagnostic performance of ReHo metrics. RESULTS: ReHo values were significantly lower in the left insula and right superior temporal gyrus, and higher in the left posterior cingulate cortex (LPCC), of DON than of non-DON patients. ReHo values were also significantly lower in the right middle temporal, left insula, and left precentral gyrus in DON than in HCs. Meanwhile, ReHo values were higher in LPCC in non-DON than in HCs. ReHo values correlated with ophthalmic examinations to varying degrees in DON. For distinguishing DON, the ReHo values in LPCC showed optimal individually (AUC = 0.843), the combination of the ReHo in both the left insula and LPCC performed better (AUC = 0.915). CONCLUSION: Spontaneous brain activity differed between TAO with and without DON, which may reflect the underlying pathological mechanism of DON. The ReHo index can be considered a diagnostic biomarker. CLINICAL RELEVANCE STATEMENT: Spontaneous brain activity in DON differed from that in TAO without DON, which may reflect the underlying pathological mechanism of DON. The ReHo index can be considered a diagnostic biomarker for early detection of DON. KEY POINTS: • Dysthyroid optic neuropathy (DON) affects brain activity, which contributes in the understanding of its visual dysfunction. • Regional homogeneity values differ between thyroid-associated ophthalmopathy with and without DON in various brain regions. • Regional homogeneity values can be used as a biomarker in the differential diagnosis of DON.

Visible-Light-Induced Annulation of Iodonium Ylides and 2-Isocyanobiaryls to Access 6-Arylated Phenanthridines.

A 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4-CzIPN)-photocatalyzed cascade arylation/cyclization reaction of 2-isocyanobiaryls and iodonium ylides was established for the synthesis of 6-arylated phenanthridines. This is the first example of employing iodonium ylides as aryl radical sources in a visible-light-induced radical cascade cyclization reaction.

Visible-Light-Mediated Annulation/Thiolation of 2-Isocyanobiaryls with Disulfides to Organoylthiophenanthridines Derivatives.

A visible-light-induced annulation/thiolation of 2-isocyanobiaryls with dialkyl(aryl)disulfides has been established, delivering a sustainable and atom-economic route to 6-organoylthiophenanthridines with wild functional group tolerance and good to excellent yields under oxidant-, base-, and transition-metal-free conditions.

Transcriptomic Complexity of Culm Growth and Development in Different Types of Moso Bamboo.

Moso bamboo is capable of both sexual and asexual reproduction during natural growth, resulting in four distinct types of culms: the bamboo shoot-culm, the seedling stem, the leptomorph rhizome, and a long-ignored culm-the outward-rhizome. Sometimes, when the outward rhizomes break through the soil, they continue to grow longitudinally and develop into a new individual. However, the roles of alternative transcription start sites (aTSS) or termination sites (aTTS) as well as alternative splicing (AS) have not been comprehensively studied for their development. To re-annotate the moso bamboo genome and identify genome-wide aTSS, aTTS, and AS in growing culms, we utilized single-molecule long-read sequencing technology. In total, 169,433 non-redundant isoforms and 14,840 new gene loci were identified. Among 1311 lncRNAs, most of which showed a positive correlation with their target mRNAs, one-third of these IncRNAs were preferentially expressed in winter bamboo shoots. In addition, the predominant AS type observed in moso bamboo was intron retention, while aTSS and aTTS events occurred more frequently than AS. Notably, most genes with AS events were also accompanied by aTSS and aTTS events. Outward rhizome growth in moso bamboo was associated with a significant increase in intron retention, possibly due to changes in the growth environment. As different types of moso bamboo culms grow and develop, a significant number of isoforms undergo changes in their conserved domains due to the regulation of aTSS, aTTS, and AS. As a result, these isoforms may play different roles than their original functions. These isoforms then performed different functions from their original roles, contributing to the transcriptomic complexity of moso bamboo. Overall, this study provided a comprehensive overview of the transcriptomic changes underlying different types of moso bamboo culm growth and development.

Allicin Alleviated LPS-Induced Mastitis via the TLR4/NF-κB Signaling Pathway in Bovine Mammary Epithelial Cells.

Dairy farming is the most important economic activity in animal husbandry. Mastitis is the most common disease in dairy cattle and has a significant impact on milk quality and yield. The natural extract allicin, which is the main active ingredient of the sulfur-containing organic compounds in garlic, has anti-inflammatory, anticancer, antioxidant, and antibacterial properties; however, the specific mechanism underlying its effect on mastitis in dairy cows needs to be determined. Therefore, in this study, whether allicin can reduce lipopolysaccharide (LPS)-induced inflammation in the mammary epithelium of dairy cows was investigated. A cellular model of mammary inflammation was established by pretreating bovine mammary epithelial cells (MAC-T) with 10 µg/mL LPS, and the cultures were then treated with varying concentrations of allicin (0, 1, 2.5, 5, and 7.5 µM) added to the culture medium. MAC-T cells were examined using RT-qPCR and Western blotting to determine the effect of allicin. Subsequently, the level of phosphorylated nuclear factor kappa-B (NF-κB) was measured to further explore the mechanism underlying the effect of allicin on bovine mammary epithelial cell inflammation. Treatment with 2.5 µM allicin considerably decreased the LPS-induced increase in the levels of the inflammatory cytokines interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) and inhibited activation of the NOD-like receptor protein 3 (NLRP3) inflammasome in cow mammary epithelial cells. Further research revealed that allicin also inhibited the phosphorylation of inhibitors of nuclear factor kappa-B-α (IκB-α) and NF-κB p65. In mice, LPS-induced mastitis was also ameliorated by allicin. Therefore, we hypothesize that allicin alleviated LPS-induced inflammation in the mammary epithelial cells of cows probably by affecting the TLR4/NF-κB signaling pathway. Allicin will likely become an alternative to antibiotics for the treatment of mastitis in cows.

LncRNA HOX transcript antisense RNA mitigates cardiac function injury in chronic heart failure via regulating microRNA-30a-5p to target KDM3A.

Long noncoding RNA HOX transcript antisense RNA (HOTAIR) has been studied in multiple diseases, but the role of HOTAIR on chronic heart failure (CHF) through the regulation of microRNA (miR)-30a-5p and lysine-specific demethylase 3A (KDM3A) remains unexplored. This research aims to probe the effects of HOTAIR on CHF progression via modulating miR-30a-5p to target KDM3A. CHF mouse model was established by intraperitoneal injection of doxorubicin. The CHF mice were then injected with high-expressed HOTAIR, miR-30a-5p or KDM3A adenovirus vectors to determine the cardiac function, oxidative stress, inflammatory response, pathological change and cardiomyocyte apoptosis. HOTAIR, miR-30a-5p, KDM3A and Bcl-2/adenovirus E1B 19kDa interacting protein 3 (BNIP3) expression in CHF mice was detected. The binding relations among HOTAIR, miR-30a-5p and KDM3A were validated. HOTAIR and KDM3A were depleted, while miR-30a-5p was augmented in CHF mice. The elevated HOTAIR or KDM3A or could improve cardiac function, mitigate oxidative stress and pathological change, reduce inflammatory factor levels and cardiomyocyte apoptosis, while the increased miR-30a-5p exerted opposite effects. The miR-30a-5p elevation could reverse the effects of enriched HOTAIR, while BNIP3 reduction abrogated the effects of KDM3A on CHF. HOTAIR sponged miR-30a-5p that targeted KDM3A. HOTAIR improves cardiac injury in CHF via modulating miR-30a-5p to target KDM3A. This study provides novel therapeutic strategies for CHF treatment.

The mystery of the life tree: the placentas†.

The placenta is the interface between the fetal and maternal environments during mammalian gestation, critically safeguarding the health of the developing fetus and the mother. Placental trophoblasts origin from embryonic trophectoderm that differentiates into various trophoblastic subtypes through villous and extravillous pathways. The trophoblasts actively interact with multiple decidual cells and immune cells at the maternal-fetal interface and thus construct fundamental functional units, which are responsible for blood perfusion, maternal-fetal material exchange, placental endocrine, immune tolerance, and adequate defense barrier against pathogen infection. Various pregnant complications are tightly associated with the defects in placental development and function maintenance. In this review, we summarize the current views and our recent progress on the mechanisms underlying the formation of placental functional units, the interactions among trophoblasts and various uterine cells, as well as the placental barrier against pathogen infections during pregnancy. The involvement of placental dysregulation in adverse pregnancy outcomes is discussed.

Secrecy performance analysis in the FSO communication system considering different eavesdropping scenarios.

In this paper, we numerically study the secrecy performance of the free-space optical (FSO) system by considering different eavesdropping scenarios. More precisely, we considered three possible eavesdropping scenarios for Eve: 1) Eve is between Alice and Bob; 2) Eve and Bob are in the same receiving plane; 3) Eve is behind Bob. We adopt the Málaga (M)-distribution channel to model atmospheric turbulence due to the presence of link blockage while considering the non-zero boresight pointing error and path loss. To do so, we obtain a novel probability density function (PDF) and cumulative distribution function (CDF) under different eavesdropping scenarios, based on which we derived the secrecy outage probability (SOP) analytical expressions as well as their asymptotic expressions at a high SNR regime. We verified the results using Monte Carlo simulations, which showed that the parameters related to atmospheric turbulence and pointing errors, as well as the location of the eavesdropper, have different effects on different eavesdropping scenarios.

Icariside II Attenuates Vascular Remodeling Via Wnt7b/CCND1 Axis.

ABSTRACT: Angioplasty often fails due to the abnormal proliferation of vascular smooth muscle cells (VSMCs). Success rates of angioplasty may increase following the administration of an agent that effectively ameliorates aberrant vascular remodeling. Icariside II (ICS-II) is a natural flavonol glycoside extract from the Chinese herbal medicine Epimedii that possesses several medicinal qualities that are beneficial in humans. Nevertheless, the role of ICS-II in addressing aberrant vascular remodeling have yet to be clarified. The current investigation studies the molecular effects of ICS-Ⅱ on balloon-inflicted neointimal hyperplasia in rats in vivo and on platelet-derived growth factor-induced vascular proliferation in primary rat aortic smooth muscle cells (VSMCs) in vitro. ICS-II was found to be as effective as rapamycin, the positive control used in this study. ICS-II inhibited neointimal formation in injured rat carotid arteries and notably reduced the expression of Wnt7b. ICS-Ⅱ significantly counteracted platelet-derived growth factor-induced VSMCs proliferation. Cell cycle analysis showed that ICS-II triggered cell cycle arrest during the G1/S transition. Western blot analysis further indicated that this cell cycle arrest was likely through Wnt7b suppression that led to CCND1 inhibition. In conclusion, our findings demonstrate that ICS-II possesses significant antiproliferative qualities that counteracts aberrant vascular neointimal hyperplasia. This phenomenon most likely occurs due to the suppression of the Wnt7b/CCND1 axis.

Design, synthesis and biological evaluation of hydrogen sulfide-releasing isochroman-4-one derivatives as new antihypertensive agent candidates.

Cardiovascular diseases are increasingly threating the global human health, hypertension is the most important risk factor for cardiovascular and cerebrovascular diseases. To improve the antihypertensive activity and cardiovascular protective effect of natural product (±)-7,8-dihydroxy-3-methyl-isochroman-4-one [(±)-XJP], a series of novel H2S-releasing isochroman-4-one derivatives were designed and synthesized by coupling hydrogen sulfide (H2S)-releasing donors with the analogs of (±)-XJP. Further, the H2S-releasing assay indicated that some target compounds showed excellent H2S generating ability. Moreover, these novel hybrids exhibited moderate to good in vitro vasodilation efficacy. Among them, the most potent compound exhibited potent in vivo antihypertensive activity with the maximum antihypertensive amplitude about 27%, which was more potent than that of the lead compound (±)-XJP. These results suggested that the hybridization of H2S-donors and (±)-XJP analogs may provide a promising approach for the discovery of novel antihypertensive agents.

Hsa_circ_0003748 promotes disease progression in rheumatic valvular heart disease by sponging miR-577.

The diagnosis and treatment of rheumatic valvular heart disease (RVHD) require substantial improvements. Studies found that circular RNAs (circRNAs) are involved in the progression of cardiovascular diseases. We screened target hsa_circ_0003748 by circRNA microarrays uploaded to a database. We used fluorescence in situ hybridization to determine the cellular location of hsa_circ_0003748. A dual-luciferase reporter gene assay revealed that has_circ_0003748 might bind the miRNA miR-577. In hVIC cells (an RVHD cell line), Cell Counting Kit-8, Transwell, and flow cytometry assays measured proliferation, migration, and cell cycle and apoptosis, respectively. We found that hsa_circ_0003748 was localized in the cytoplasm; hsa_circ_0003748 promoted the proliferation and migration of hVIC cells, arrested the cell cycle in the G2/M phase, and inhibited apoptosis. These phenomena may result from hsa_circ_0003748 promoting RVHD after sponging miR-577. Bioinformatic analysis revealed that hsa_circ_0003748 might affect RVHD progression by affecting transcription and the MAPK signaling pathway, the Ras signaling pathway, the cAMP signaling pathway, the Rap1 signaling pathway, and other signaling pathways.

Relationship between chronic periodontitis and inflammatory cytokines in patients undergoing maintenance hemodialysis.

OBJECTIVES: To investigate the correlation between serum and gingival crevicular fluid (GCF) levels of inflammatory cytokines and the association with periodontal parameters in patients with maintenance hemodialysis (MHD) and healthy control. MATERIALS AND METHODS: Patients who were undergoing MHD were enrolled as the MHD group. Healthy individuals who underwent oral examination were selected as the control group after matching for the MHD group. All participants underwent a full-mouth periodontal evaluation, and the levels of eight inflammatory cytokines, including IL-1ß, IL-17, IL-6, IL-8, and tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-8 (MMP-8), and C-reactive protein (CRP), in the GCF and serum were measured. RESULTS: A total of 63 MHD patients and 75 healthy persons were included. The prevalence of moderate/severe periodontitis was significantly higher in the MHD group than in the control group (88.9 vs. 66.7%, P < 0.05). The GCF levels of CRP, TNF-α, MCP-1, and MMP-8 were higher in patients in the MHD group with moderate/severe periodontitis than in the control group (P < 0.05). Serum CRP, MCP-1, TNF-α, and MMP-8 levels were positively correlated with the GCF CRP levels (P < 0.05). The GCF and serum CRP levels were positively correlated with the periodontal clinical parameters (P < 0.05). CONCLUSIONS: Serum CRP, MCP-1, TNF-α, and MMP-8 may relate with the GCF CRP levels. The GCF and serum CRP levels correlated positively with the periodontal clinical parameters, including the VPI, PPD, and CAL, indicating that CRP may play an important role between periodontitis and ESRD. CLINICAL RELEVANCE: The present study indicated that GCF and serum CRP levels correlated positively with the periodontal clinical parameters, and the CRP levels may be selected as an indicator to evaluate the severity of inflammation and the effectiveness, prognosis of periodontal treatment in ESRD patients.