Long noncoding RNA MALAT1 is dynamically regulated in leader cells during collective cancer invasion.

Cancer cells collectively invade using a leader-follower organization, but the regulation of leader cells during this dynamic process is poorly understood. Using a dual double-stranded locked nucleic acid (LNA) nanobiosensor that tracks long noncoding RNA (lncRNA) dynamics in live single cells, we monitored the spatiotemporal distribution of lncRNA during collective cancer invasion. We show that the lncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) is dynamically regulated in the invading fronts of cancer cells and patient-derived spheroids. MALAT1 transcripts exhibit distinct abundance, diffusivity, and distribution between leader and follower cells. MALAT1 expression increases when a cancer cell becomes a leader and decreases when the collective migration process stops. Transient knockdown of MALAT1 prevents the formation of leader cells and abolishes the invasion of cancer cells. Taken together, our single-cell analysis suggests that MALAT1 is dynamically regulated in leader cells during collective cancer invasion.

Transcriptomic profiling and gene network analysis revealed regulatory mechanisms of bract development in Bougainvillea glabra.

BACKGROUND: Bracts are important for ornamental plants, and their developmental regulation process is complex; however, relatively little research has been conducted on bracts. In this study, physiological, biochemical and morphological changes in Bougainvillea glabra leaves, leaf buds and bracts during seven developmental periods were systematically investigated. Moreover, transcriptomic data of B. glabra bracts were obtained using PacBio and Illumina sequencing technologies, and key genes regulating their development were screened. RESULTS: Scanning electron microscopy revealed that the bracts develop via a process involving regression of hairs and a color change from green to white. Transcriptome sequencing revealed 79,130,973 bp of transcript sequences and 45,788 transcripts. Differential gene expression analysis revealed 50 expression patterns across seven developmental periods, with significant variability in transcription factors such as BgAP1, BgFULL, BgCMB1, BgSPL16, BgSPL8, BgDEFA, BgEIL1, and BgBH305. KEGG and GO analyses of growth and development showed the involvement of chlorophyll metabolism and hormone-related metabolic pathways. The chlorophyll metabolism genes included BgPORA, BgSGR, BgPPH, BgPAO and BgRCCR. The growth hormone and abscisic acid signaling pathways involved 44 and 23 homologous genes, and coexpression network analyses revealed that the screened genes BgAPRR5 and BgEXLA1 are involved in the regulation of bract development. CONCLUSIONS: These findings improve the understanding of the molecular mechanism of plant bract development and provide important guidance for the molecular regulation and genetic improvement of the growth and development of ornamental plants, mainly ornamental bracts.

Fabrication of Self-Wrinkling Polymer Films with Tunable Patterns through an Interfacial-Fuming-Induced Surface Instability Process.

Inspired by the superglue fuming method for fingerprint collection, this study developed a novel interfacial-fuming-induced surface instability process to generate wrinkled patterns on polymeric substrates. High-electronegativity groups are introduced on the substrate surface to initiate the polymerization of monomer vapors, such as ethyl cyanoacrylate, which results in the formation of a stiff poly(ethyl cyanoacrylate) capping layer. Moreover, interfacial polymerization resulted in the covalent bonding of the substrate, which led to the volumetric shrinkage of the composite and the accumulation of compressive strain. This process ultimately resulted in the development and stabilization of wrinkled surface morphologies. The authors systematically examined parameters such as the modulus of the epoxy substrate, prestrain, the flow rate of fuming, and operating temperature. The aforementioned technique can be easily applied to architectures with complex outer morphologies and inner surfaces, thereby enabling the construction of surface patterns under ambient conditions without vacuum limitations or precise process control. This study is the first to combine fuming-induced interfacial polymerization with surface instability to create robust wrinkles. The proposed method enables the fabrication of intricate microwrinkled patterns and has considerable potential for use in various practical applications, including microfluidics, optical components, bioinspired adhesive devices, and interfacial engineering.

Decreasing circ_0014614 promotes the differentiation of bone marrow flineage cells into megakaryocytes in essential thrombocythemia via activiation of miR-138-5p/caspase3 axis.

BACKGROUND: Circular RNAs (circRNA) are pivotal in hematological diseases. Previous study showed that circ_0014614 (circDAP3) was significantly underexpressed in bone marrow-derived exosomes from essential thrombocythemia (ET) patients, affecting the differentiation of bone marrow lineage cells into megakaryocytes. METHODS: Fluorescence in situ hybridization (FISH) was used to display circ_0014614's primary cytoplasmic location in K562 cells. Cytoscape software was used to predict the circRNA-miRNA-mRNA networks, and their expression at the cellular level was detected by Quantitative reverse transcription-polymerase chain reaction (qRT-PCR). qRT-PCR was utilized to detect the expression levels of circ_0014614，miR-138-5p and caspase3 mRNA. Western blot was used to determine the protein levels of GATA-1, RUNX-1, NF-E2, CD41 and caspase3. The proliferation of K562 cells was assessed using the Cell Counting Kit-8 (CCK-8) Assay. Furthermore, the interplay between miR-138-5p and circ_0014614 or caspase3 was elucidated through a Dual-luciferase reporter assay. RESULTS: FISH assay indicated circ_0014614's primary cytoplasmic location in K562 cells. In ET bone marrow and K562 cells, circ_0014614 and caspase3 were down-regulated, whereas miR-138-5p saw a significant surge. Overexpressing circ_0014614 curtailed K562 cells' proliferation and differentiation. Further, circ_0014614 targeted miR-138-5p, with heightened miR-138-5p levels counteracting circ_0014614's inhibition. MiR-138-5p further targeted caspase3, and caspase3 silencing neutralized suppressed miR-138-5p's effects on K562 cell differentiation. CONCLUSION: Circ_0014614 was down-regulated in ET bone marrow and bone marrow lineage cells, and upregulating circ_0014614 can inhibit bone marrow lineage cells' proliferation and differentiation into megakaryocytes. Mechanistically, circ_0014614 functioned as ceRNA via sponging miR-138-5p and alleviated the inhibitory effect of miR-138-5p on its target caspase3, which potentially deters tumor activity in ET.

Independent association between IVC filter placement and VTE risk in patients with upper gastrointestinal bleeding and isolated distal DVT: A retrospective cohort study.

BACKGROUND: The placement of inferior vena cava (IVC) filters often emerges as an alternative preventative measure against pulmonary embolism in patients with upper gastrointestinal (GI) bleeding and isolated distal deep vein thrombosis (DVT). We aimed to investigate the association of IVC filter placement and the incidence of venous thromboembolism (VTE) recurrence in this patient population. METHODS: We performed a retrospective cohort study including 450 patients with upper GI bleeding and isolated distal DVT. Propensity score matching using logistic regression was conducted to mitigate potential selection bias. Logistic regression models and additional sensitivity analyses were conducted to estimate the association between IVC filter implantation and VTE recurrence. Interaction and stratified analyses were also performed according to the background covariates. RESULTS: Patients who underwent IVC filter placement were significantly younger than patients in the surveillance group (55.8 ± 9.0 vs 58.4 ± 11.2 years, p = 0.034). Patients in the IVC filter group demonstrated a higher distal thrombus burden. The VTE recurrence composite was significantly higher in patients who underwent IVC filter placement (44.1% [45/102] vs 25% [87/348], p < 0.001). Unmatched crude logistic regression analysis identified a significant association between IVC filter placement and VTE recurrence composite (OR = 2.37; 95% CI, 1.50-3.75). Sensitivity analyses yielded congruent outcomes. CONCLUSION: This study revealed an increased risk of VTE recurrence among patients receiving IVC filter placement, suggesting that IVC filter placement may not be suitable as a primary treatment for patients with upper GI bleeding and isolated distal DVT.

SYNBIP: synthetic binding proteins for research, diagnosis and therapy.

The success of protein engineering and design has extensively expanded the protein space, which presents a promising strategy for creating next-generation proteins of diverse functions. Among these proteins, the synthetic binding proteins (SBPs) are smaller, more stable, less immunogenic, and better of tissue penetration than others, which make the SBP-related data attracting extensive interest from worldwide scientists. However, no database has been developed to systematically provide the valuable information of SBPs yet. In this study, a database named 'Synthetic Binding Proteins for Research, Diagnosis, and Therapy (SYNBIP)' was thus introduced. This database is unique in (a) comprehensively describing thousands of SBPs from the perspectives of scaffolds, biophysical & functional properties, etc.; (b) panoramically illustrating the binding targets & the broad application of each SBP and (c) enabling a similarity search against the sequences of all SBPs and their binding targets. Since SBP is a human-made protein that has not been found in nature, the discovery of novel SBPs relied heavily on experimental protein engineering and could be greatly facilitated by in-silico studies (such as AI and computational modeling). Thus, the data provided in SYNBIP could lay a solid foundation for the future development of novel SBPs. The SYNBIP is accessible without login requirement at both official (https://idrblab.org/synbip/) and mirror (http://synbip.idrblab.net/) sites.

Polypyridyl Ru(II) or cyclometalated Ir(III) functionalized architectures for photocatalysis.

The chemistry of polypyridyl Ru(II) and cyclometalated Ir(III) derivatives provides long-lasting interest to researchers due to the inherent advantage of their triplet states in a variety of photoactivities. The introduction of Ru(N^N)3 and Ir(C^N)2(X^N) modules into well-defined architectures extends the research areas of both photoactive metal complexes and network chemistry, generating a lot of new opportunities with interesting structural aesthetics and profound functional possibilities. The rapid development of research in integrating Ru(II) or Ir(III) metallotecons into the architectures has been apparent in recent years which makes this a fascinating subject for reviewing. This review focuses on the design and syntheses of Ru(N^N)3 and Ir(C^N)2(X^N) functionalized architectures of metal-organic frameworks (MOFs), covalent-organic frameworks (COFs), metallasupramolecules, organic supramolecules and supramolecular organic frameworks (SOFs). Furthermore, the photocatalytic applications including the hydrogen evolution reaction (HER), carbon dioxide reduction reaction (CO2RR), photocatalytic oxidation and photoredox catalysis of organic transformation are also presented.

NRPS-like ATRR in Plant-Parasitic Nematodes Involved in Glycine Betaine Metabolism to Promote Parasitism.

Plant-parasitic nematodes (PPNs) are among the most serious phytopathogens and cause widespread and serious damage in major crops. In this study, using a genome mining method, we identified nonribosomal peptide synthetase (NRPS)-like enzymes in genomes of plant-parasitic nematodes, which are conserved with two consecutive reducing domains at the N-terminus (A-T-R1-R2) and homologous to fungal NRPS-like ATRR. We experimentally investigated the roles of the NRPS-like enzyme (MiATRR) in nematode (Meloidogyne incognita) parasitism. Heterologous expression of Miatrr in Saccharomyces cerevisiae can overcome the growth inhibition caused by high concentrations of glycine betaine. RT-qPCR detection shows that Miatrr is significantly upregulated at the early parasitic life stage (J2s in plants) of M. incognita. Host-derived Miatrr RNA interference (RNAi) in Arabidopsis thaliana can significantly decrease the number of galls and egg masses of M. incognita, as well as retard development and reduce the body size of the nematode. Although exogenous glycine betaine and choline have no obvious impact on the survival of free-living M. incognita J2s (pre-parasitic J2s), they impact the performance of the nematode in planta, especially in Miatrr-RNAi plants. Following application of exogenous glycine betaine and choline in the rhizosphere soil of A. thaliana, the numbers of galls and egg masses were obviously reduced by glycine betaine but increased by choline. Based on the knowledge about the function of fungal NRPS-like ATRR and the roles of glycine betaine in host plants and nematodes, we suggest that MiATRR is involved in nematode-plant interaction by acting as a glycine betaine reductase, converting glycine betaine to choline. This may be a universal strategy in plant-parasitic nematodes utilizing NRPS-like ATRR to promote their parasitism on host plants.

Revolutionizing sanitation: Valorizing fecal slags through co-digesting food waste at high-solid content and dosing metallic nanomaterials for anaerobic digestion stability.

To achieve the UN Sustainable Development Goals (SDGs) and the China Toilet Revolution on a global scale, it is crucial to implement a decentralized sanitation management system in developing countries. Fecal slags (FS) generated from septic tanks of toilets pose a challenge for remote villages. This study sought to resourcefully utilize FS through co-digesting with food waste (FW) under high-solid anaerobic co-digestion (HSAD). Besides, two metallic nanomaterials, nano-zerovalent iron (nZVI) and magnetite (Fe3O4), were employed to demonstrate the practical improvement of HSAD. The results showed that nZVI-dosed digesters produced the highest cumulative methane of 295.72 mL/gVS, 371.36 mL/gVS, 360.53 mL/gVS and 296.64 mL/gVS in 10%, 15%, 20% and 25% TS content, respectively, which was 1.15, 1.22, 1.16, 1.12 times higher than Fe3O4 dosed digesters. This increment could be ascribed to the simultaneous production of H2 from Fe2+ release from nZVI and the enrichment of homoacetogen. Changes in carbon degradation and methanogenic pathways, which facilitated stability under high TS contents, were observed. At low solid digestion (10% TS), Syntrophomonas cooperated with Methanosarcina and Methanobacterium to metabolize butyrate and propionate. However, due to the buildup of total ammonia nitrogen and volatile fatty acids, acetoclastic methanogens were inhibited in the high-solid digesters (15%, 20% and 25% TS). Consequently, a more resilient and highly tolerant Syntrophaceticus, alongside hydrogenotrophic methanogens such as Methanoculleus and Methanobrevibacter, maintained stability in the harsh environment.

Clinical efficacy of HI-NPPV in the treatment of AECOPD combined with severe type II respiratory failure. / HI-NPPV治疗AECOPD合并严重II型呼吸衰竭的临床疗效.

OBJECTIVES: Patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) combined with severe type II respiratory failure have a high probability of ventilation failure using conventional non-invasive positive pressure ventilation (NPPV). This study aims to investigate the clinical efficacy of high intensity NPPV (HI-NPPV) for the treatment of AECOPD combined with severe type II respiratory failure. METHODS: The data of patients with AECOPD combined with severe type II respiratory failure (blood gas analysis pH≤7.25) treated with NPPV in the Second Affiliated Hospital of Chongqing Medical University from July 2013 to July 2023 were collected to conduct a retrospective case-control study. The patients were divided into 2 groups according to the inspired positive airway pressure (IPAP) used during the NPPV treatment: a NPPV group (IPAP<20 cmH2O, 1 cmH2O=0.098 kPa) and a HI-NPPV group (20 cmH2O≤IPAP< 30 cmH2O). Ninety-nine and 95 patients were included in the NPPV group and the HI-NPPV group, respectively. A total of 86 pairs of data were matched using propensity score matching (PSM) for data matching. The primary outcome indexes (mortality and tracheal intubation rate) and secondary outcome indexes [blood gas analysis pH, arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2), adverse reaction rate, and length of hospitalization] were compared between the 2 groups. RESULTS: The tracheal intubation rates of the NPPV group and the HI-NPPV group were 6.98% and 1.16%, respectively, and the difference between the 2 groups was statistically significant (χ2=4.32, P<0.05); the mortality of the NPPV group and the HI-NPPV group was 23.26% and 9.30%, respectively, and the difference between the 2 groups was statistically significant (χ2=11.64, P<0.01). The PaO2 at 24 h and 48 h after treatment of the HI-NPPV group was higher than that of the NPPV group, and the PaCO2 of the HI-NPPV group was lower than that of the NPPV group, and the differences were statistically significant (all P<0.05). The differences of pH at 24 h and 48 h after treatment between the 2 groups were not statistically significant (both P>0.05). The differences between the 2 groups in adverse reaction rate and hospitalization length were not statistically significant (both P>0.05). CONCLUSIONS: HI-NPPV can reduce mortality and tracheal intubation rates by rapidly improving the ventilation of patients with AECOPD combined with severe type II respiratory failure. This study provides a new idea for the treatment of patients with AECOPD combined with severe type II respiratory failure.

Prenatal Diagnosis of Oral Teratoma by Ultrasound.

A pregnant woman had a normal second-trimester anatomic survey at 22 weeks gestation. She was revealed to have a fetal oral mass with polyhydramnios and invisible stomach bubble by ultrasound at 28 weeks. A 50 mm × 36 mm × 42 mm, solid mass was found in the fetal mouth, filling the entire oral cavity. Fetal magnetic resonance imaging showed a homogeneous solid mass in the oral cavity compressing the hypopharynx. At 33 weeks, preterm labor occurred because of the continuation of increased amniotic fluid volume, and a female infant was vaginally delivered. The infant died shortly after tracheal intubation attempt failed. Autopsy confirmed the prenatal sonographic finding. The final pathologic diagnosis was oral immature teratoma. Our study indicates that although oral teratomas are rare, they are readily apparent at prenatal sonographic examinations. Respiratory compromise is the frequent complication of oral teratomas, which is associated with high perinatal mortality.

Six Express Sequence Tag-Simple Sequence Repeat Primers Reveal Genetic Diversity in the Cultivars of Three Zanthoxylum Species.

Zanthoxylum (Sichuan pepper), with its rich cultivars, has long been widely cultivated in China for its unique seasoning and medicinal uses, but most of its cultivars have similar morphological characteristics. Therefore, we hypothesized that the genetic diversity of Zanthoxylum cultivars is low because of their apomixis and long cultivation history. In this study, we aimed to investigate the genetic diversity of three Zanthoxylum species on the cultivar level based on express sequence tag-simple sequence repeat (EST-SSR) primers. In total, 121 samples of three Zanthoxylum species (Z. bungeanum, Z. armatum and Z. piperitum) were collected from different areas in China for genetic diversity analysis. A total of six specificity and polymorphism EST-SSR primers, which we selected from among 120 primers based on two transcriptomes (Z. bungeanum, Z. armatum) in our earlier study, were used to evaluate genetic diversity based on capillary electrophoresis technology. The results of our analysis using the unweighted pair group method with arithmetic mean (UPGMA) indicated that most of the samples are clustered in one clade in the UPGMA dendrogram, and the average genetic distance was 0.6409. Principal component analysis (PCA) showed that Z. piperitum may have a closer genetic relationship with Z. bungeanum than with Z. armatum. An analysis of molecular variation (AMOVA) showed that the genetic variation mainly stemmed from individuals within populations; the genetic differentiation coefficient (PhiPT) was 0.429, the gene flow (Nm) between populations was 0.333, and the differences among populations were not significant (p > 0.001). For the intraspecific populations of ZB, the percentage of genetic variation was 53% among populations and 47% within populations, with non-significant differences between populations (p > 0.001). The genetic differentiation coefficient (PhiT) was 0.529, and the gene flow (Nm) was 0.223. For the intraspecific populations of ZA, the results indicated that the percentage of genetic variation was 29% among populations and 71% within populations, with non-significant differences between populations (p > 0.001); the genetic differentiation coefficient (PhiPT) was 0.293, and the gene flow (Nm) was 0.223. Through genetic structure analysis (GSA), we predicted that these 121 samples belonged to two optimal subgroups, which means that all the samples probably originated from two gene pools. Above all, this indicated that the genetic diversity of the 121 Zanthoxylum samples was relatively low at both the species and cultivar levels, a finding which was consistent with our initial assumptions. This study provides a reference, with molecular-level data, for the further identification of Zanthoxylum species.

Natural products of pentacyclic triterpenoids: from discovery to heterologous biosynthesis.

Covering: up to 2022Pentacyclic triterpenoids are important natural bioactive substances that are widely present in plants and fungi. They have significant medicinal efficacy, play an important role in reducing blood glucose and protecting the liver, and have anti-inflammatory, anti-oxidation, anti-fatigue, anti-viral, and anti-cancer activities. Pentacyclic triterpenoids are derived from the isoprenoid biosynthetic pathway, which generates common precursors of triterpenes and steroids, followed by cyclization with oxidosqualene cyclases (OSCs) and decoration via cytochrome P450 monooxygenases (CYP450s) and glycosyltransferases (GTs). Many biosynthetic pathways of triterpenoid saponins have been elucidated by studying their metabolic regulation network through the use of multiomics and identifying their functional genes. Unfortunately, natural resources of pentacyclic triterpenoids are limited due to their low content in plant tissues and the long growth cycle of plants. Based on the understanding of their biosynthetic pathway and transcriptional regulation, plant bioreactors and microbial cell factories are emerging as alternative means for the synthesis of desired triterpenoid saponins. The rapid development of synthetic biology, metabolic engineering, and fermentation technology has broadened channels for the accumulation of pentacyclic triterpenoid saponins. In this review, we summarize the classification, distribution, structural characteristics, and bioactivity of pentacyclic triterpenoids. We further discuss the biosynthetic pathways of pentacyclic triterpenoids and involved transcriptional regulation. Moreover, the recent progress and characteristics of heterologous biosynthesis in plants and microbial cell factories are discussed comparatively. Finally, we propose potential strategies to improve the accumulation of triterpenoid saponins, thereby providing a guide for their future biomanufacturing.

Comprehensive analysis of metabolome and transcriptome reveals the mechanism of color formation in different leave of Loropetalum Chinense var. Rubrum.

BACKGROUND: Loropetalum chinense var. rubrum (L. chinense var. rubrum) is a precious, coloured-leaf native ornamental plant in the Hunan Province. We found an L. chinense var. rubrum tree with three different leaf colours: GL (green leaf), ML (mosaic leaf), and PL (purple leaf). The mechanism of leaf coloration in this plant is still unclear. Therefore, this study aimed to identify the metabolites and genes involved in determining the colour composition of L. chinense var. rubrum leaves, using phenotypic/anatomic observations, pigment content detection, and comparative metabolomics and transcriptomics. RESULTS: We observed that the mesophyll cells in PL were purple, while those in GL were green and those in ML were a mix of purple-green. The contents of chlorophyll a, b, carotenoids, and total chlorophyll in PL and ML were significantly lower than those in GL. While the anthocyanin content in PL and ML was significantly higher than that in GL. The metabolomics results showed the differences in the content of cyanidin 3-O-glucoside, delphinidin 3-O-glucoside, cyanidin 3,5-O-diglucoside, pelargonidin, and petunidin 3,5-diglucoside in ML, GL, and PL were significant. Considering that the change trend of anthocyanin content change was consistent with the leaf colour difference, we speculated that these compounds might influence the colour of L. chinense var. rubrum leaves. Using transcriptomics, we finally identified nine differentially expressed structural genes (one ANR (ANR1217); four CYP75As (CYP75A1815, CYP75A2846, CYP75A2909, and CYP75A1716); four UFGTs (UFGT1876, UFGT1649, UFGT1839, and UFGT3273) and nine transcription factors (two MYBs (MYB1057 and MYB1211), one MADS-box (MADS1235), two AP2-likes (AP2-like1779 and AP2-like2234), one bZIP (bZIP3720), two WD40s (WD2173 and WD1867) and one bHLH (bHLH1631) that might be related to flavonoid biosynthesis and then impacted the appearance of colour in L. chinense var. rubrum leaves. CONCLUSION: This study revealed potential molecular mechanisms associated with leaf coloration in L. chinense var. rubrum by analyzing differential metabolites and genes related to the anthocyanin biosynthesis pathway. It also provided a reference for research on leaf colour variation in other ornamental plants.

Life events and parent style for mental health in children: a cross-sectional study.

BACKGROUND: Life events and parenting styles might play an important role in children's mental health. AIMS: This study aims to explore how life events and parenting styles influence children's mental health based on a Chinese sample. METHODS: A total of 3535 participants had at least one mental disorder (positive group), while a total of 3561 participants had no mental disorders (negative group). The Child Behavior Checklist (CBCL), Adolescent Self-Rating Life Events Check List (ASLEC) and Egna Minnen Beträffande Uppfostran (EMBU) were used for screening these two groups. RESULTS: CBCL total scores differed significantly by sex in the Positive group according to the Mann-Whitney tests (Z = -5.40, p < 0.001). Multiple regression analyses showed that the dimensions of punishment (p = 0.014) and other (p = 0.048) in the ASLEC scale can significantly predict CBCL total scores in the Positive group. Sex, age and overprotection from the father were risk factors (p < 0.001) according to binary logistic regression. CONCLUSIONS: Life events and parenting styles may have impacts on mental health. Fathers play a very important role in children's growth. Punitive education and fathers' overprotection might be risk factors for children's mental health. IMPACT: It is a large sample (3535) study of Chinese children and adolescents It provides evidence that life events and parenting styles have impacts on mental health and that fathers play a very important role in children's growth. It is conducive to the development of interventions for the mental health of children and adolescents.

Muscone inhibits angiotensin II-induced cardiac hypertrophy through the STAT3, MAPK and TGF-ß/SMAD signaling pathways.

BACKGROUND: Muscone is a chemical monomer derived from musk. Although many studies have confirmed the cardioprotective effects of muscone, the effects of muscone on cardiac hypertrophy and its potential mechanisms are unclear.The aim of the present study was to investigate the effect of muscone on angiotensin (Ang) II-induced cardiac hypertrophy. METHODS AND RESULTS: In the present study, we found for the first time that muscone exerted inhibitory effects on Ang II-induced cardiac hypertrophy and cardiac injury in mice. Cardiac function was analyzed by echocardiography measurement, and the degree of cardiac fibrosis was determined by the quantitative real-time polymerase chain reaction (qRT-PCR), Masson trichrome staining and western blot assay. Secondly, qRT-PCR experiment showed that muscone attenuated cardiac injury by reducing the secretion of pro-inflammatory cytokines and promoting the secretion of anti-inflammatory cytokines. Moreover, western blot analysis found that muscone exerted cardio-protective effects by inhibiting phosphorylation of key proteins in the STAT3, MAPK and TGF-ß/SMAD pathways. In addition, CCK-8 and determination of serum biochemical indexes showed that no significant toxicity or side effects of muscone on normal cells and organs. CONCLUSIONS: Muscone could attenuate Ang II-induced cardiac hypertrophy, in part, by inhibiting the STAT3, MAPK, and TGF-ß/SMAD signaling pathways.

Seasonal characteristics of ambient temperature variation (DTR, TCN, and TV0-t) and air pollutants on childhood asthma attack in a dry and cold city in China.

Very few researches have concentrated on a variety of time scales to evaluate the association between temperature variation (TV) and childhood asthma (CA), and the evidence for the interaction of air pollutants on this association is lacking. In this study, we aim to estimate the relative risks (RRs) of CA due to TV by following metrics: diurnal temperature range (DTR), temperature changes between neighboring days (TCN), and temperature variability (TV0-t); to quantify the seasonal attributable fraction (AF) and number (AN) of CA due to TV; to examine the interactive effects of the TV and air pollutants on CA in different seasons. We mainly applied distributed lagged nonlinear model (DLNM) and conditional Poisson models to evaluate the associations between TV and outpatient visits for CA during 2014-2019 in Lanzhou, China. Additionally, the bivariate response surface model was used to examine the interplay effect of air pollutants. We found that in warm season, the risks of DTR maximum at lag5 (RR = 1.073, 95% CI: 1.017-1.133); TCN showed protective effect. In cold season, the risks of DTR peaked at lag8 (RR = 1.063, 95% CI: 1.027-1.100); the risks of TCN maximum at lag0 (RR = 1.058 95% CI: 1.009-1.109); the estimation of total cases maximized at TV0-4 in cold season (RR = 1.039 at TV0-3, 95% CI: 1.001, 1.077) and was the lowest at TV0-1 in warm season (RR = 0.999, 95% CI: 0.969, 1.030). In addition, the response surface model graphically pictured ambient air pollutants enhanced the DTR/TV0-4-CA effect for girls. In conclusion, the RRs of CA are markedly increased by TV exposure, particularly during the colder months. A combined evaluation of DTR, TCN, TV0-5∼TV0-6, NO2, SO2, and PM2.5 should be used to identify the adverse effects of TV on CA.

Impact of initial dialysis modality on the survival of patients with ESRD: a propensity-score-matched study.

BACKGROUND: Studies comparing the survival of hemodialysis (HD) and peritoneal dialysis (PD) patients are controversial. This study evaluated the impact of initial dialysis modality on the survival of patients with end-stage renal disease (ESRD) in a matched-pair cohort. METHODS: A retrospective cohort study was performed on ESRD patients who initiated renal replacement treatment between January 1, 2010, and December 31, 2018. Propensity score matching was applied to balance the baseline conditions, and multivariate Cox regression analysis was applied to compare mortality between HD and PD patients and evaluate correlations between mortality and various baseline characteristics. Subgroup analysis was performed with respect to diabetes status. RESULTS: There were 739 patients in our center in the Chinese National Renal Data System (CNRDS) between 2010 and 2018. Of these, 125 PD patients were matched with 125 HD patients. The 1-, 2-, and 3-year survival rates were 96.5%, 90.7%, and 82.5%, respectively, in the HD group and 99.5%, 97.8%, and 92.5%, respectively, in the PD group (log-rank P < 0.001). Among the propensity score-matched cohorts, no significant differences in Kaplan-Meier curves were observed between the two groups (log-rank P = 0.514). Age at dialysis initiation, CCI, congestive heart failure and cerebrovascular disease were risk factors in the multivariable-adjusted model. In subgroups defined by diabetes status, the Kaplan‒Meier survival curve showed that PD survival was significantly higher than that of HD (log-rank P = 0.022). CONCLUSIONS: HD and PD were not significantly different regarding the survival of patients with ESRD. PD was associated with better survival in diabetic ESRD patients.

Role of SIRT3 in neurological diseases and rehabilitation training.

Sirtuin3 (SIRT3) is a deacetylase that plays an important role in normal physiological activities by regulating a variety of substrates. Considerable evidence has shown that the content and activity of SIRT3 are altered in neurological diseases. Furthermore, SIRT3 affects the occurrence and development of neurological diseases. In most cases, SIRT3 can inhibit clinical manifestations of neurological diseases by promoting autophagy, energy production, and stabilization of mitochondrial dynamics, and by inhibiting neuroinflammation, apoptosis, and oxidative stress (OS). However, SIRT3 may sometimes have the opposite effect. SIRT3 can promote the transfer of microglia. Microglia in some cases promote ischemic brain injury, and in some cases inhibit ischemic brain injury. Moreover, SIRT3 can promote the accumulation of ceramide, which can worsen the damage caused by cerebral ischemia-reperfusion (I/R). This review comprehensively summarizes the different roles and related mechanisms of SIRT3 in neurological diseases. Moreover, to provide more ideas for the prognosis of neurological diseases, we summarize several SIRT3-mediated rehabilitation training methods.

The association between endocrine disrupting chemicals and MAFLD: Evidence from NHANES survey.

Previous studies on the association of endocrine-disrupting chemicals (EDCs) with metabolic dysfunction-associated fatty liver disease (MAFLD) are very limited. This study analyzed the association of EDCs exposure with MAFLD among 5073 American adults from the 2017-2018 National Health and Nutrition Examination Survey. The results showed that increased exposure to 3 EDCs metabolites (namely As, DiNP and PFOA) were significantly associated with MAFLD, the odds ratio of which were 1.819 (95% CI: 1.224, 2.702), 1.959 (95% CI: 1.224, 3.136) and 2.148 (95% CI: 1.036, 4.456), respectively. Further, the bayesian kernel machine regression model also revealed that phthalates exposure was strongly connected with the MAFLD, particularly in females and the elderly over 65. Moderating effect analysis suggested that higher body mass index (BMI) and inflammatory diet habit (indicated by dietary inflammatory index) strengthened the association between EDCs and MAFLD, whereas population with higher level of insulin sensitivity showed lower risk. In conclusion, our results suggest that either single or combined exposure to EDCs metabolites is link to MAFLD. Our findings also encourage people to sustain a healthy diet, normal levels of insulin sensitivity and BMI, which may help to alleviate the association of MAFLD risk in exposure to EDCs. These results also help us to better understand the association of EDCs and MAFLD and provide effective evidences for preventing MAFLD from the EDCs exposure aspect.