Functional and Multi-Omics Effects of an Optimized CRISPR-Mediated FURIN Depletion in U937 Monocytes.

The pro-protein convertase FURIN (PCSK3) is implicated in a wide range of normal and pathological biological processes such as infectious diseases, cancer and cardiovascular diseases. Previously, we performed a systemic inhibition of FURIN in a mouse model of atherosclerosis and demonstrated significant plaque reduction and alterations in macrophage function. To understand the cellular mechanisms affected by FURIN inhibition in myeloid cells, we optimized a CRISPR-mediated gene deletion protocol for successfully deriving hemizygous (HZ) and nullizygous (NZ) FURIN knockout clones in U937 monocytic cells using lipotransfection-based procedures and a dual guide RNA delivery strategy. We observed differences in monocyte and macrophage functions involving phagocytosis, lipid accumulation, cell migration, inflammatory gene expression, cytokine release patterns, secreted proteomics (cytokines) and whole-genome transcriptomics between wild-type, HZ and NZ FURIN clones. These studies provide a mechanistic basis on the possible roles of myeloid cell FURIN in cardiovascular disorders.

Novel evaluation method based on critical arch height as instability criterion for sustaining arch locked-segment-type slopes.

In sustaining arch locked-segment-type slopes, natural soil arches play a key anti-sliding role in the slope's evolution. In this study, a self-developed model test device was used to simulate the whole process of deformation evolution of sustaining arch locked-segment-type slopes, and the formation of natural sustaining arch and its locking control effect on slope stability were studied. The test results show that the continuous formation and progressive destruction of the sustaining arch were observed. The sustaining arch formed in the second time has the best locking effect, and the anti-sliding force reaches its stress peak point. However, the slope is not in a critically unstable state, instead, the stress is continuously adjusted to form a larger range of soil arch to resist the slope thrust. Consequently, the slope destabilizes until the ultimate shear strength of arch foots is exceeded, at which point the critical arch height of the arch is reached. The critical arch height mechanical model for slope stability analysis was developed based on the soil arching effect and limit equilibrium theory. The applicability of the model was demonstrated by the physical test and Xintan slope data, which can provide some guidance for early warning of landslides.

Adequate iodine nutrition and higher salt intake in Chinese adults aged 18-59 years recommended by international organizations.

Iodine deficiency and excessive salt intake have adverse health effects. This study evaluated the iodine level and salt intake in Chinese adults aged 18-59 years after implementing the salt reduction program and compared with both the World Health Organization (WHO) and Chinese recommendations. Adults aged 18-59 years were randomly selected using multi-stage stratified random sampling in coastal urban area (CUA), non-coastal urban area (Non-CUA), coastal rural area (CRA), and non-coastal rural area (Non-CRA) of Fujian Province, China. Iodine, sodium, and creatinine concentrations in spot urine samples were measured. Knudsen equation was used to determine 24-h urinary iodine and sodium excretion. The median urinary iodine concentration (mUIC) and urinary sodium concentration (mUNaC) among adults (n = 3513) were 132.0 µg/L and 4.0 g/d, respectively. The mUIC and median daily iodine intake in CUA, Non-CUA, CRA and Non-CRA were 112.1, 127.5, 128.5, 167.5 µg/L and 189.6, 182.5, 199.4, 236.0 µg/d, respectively. The mUNaC and median daily salt intake (mDSI) in these four areas were 2.4, 2.8, 2.9, 2.9 g/L and 9.8, 10.4, 10.4, 10.6 g/d, respectively. The mUIC and DII of residents were higher in the Non-CRA than in the other three areas (P < 0.05). The UNaC and DSI of residents were lower in the CUA than in the other three areas (P < 0.05). The logistic regression demonstrated that the people living in CUA and Non-CUA consumed less salt compared with those in Non-CRA. Except for Non-CUA, the DII was lower (< 150 µg/d) among women of childbearing age in the low-salt intake group (< 5 g/d) compared with the high-salt intake group (≥ 5 g/d) (P < 0.05). Iodine nutrition in Chinese adults aged 18-59 years was sufficient, but the salt intake was substantially higher than the WHO and Chinese recommendations. Further policy implementation is needed to reduce salt intake and improve the monitoring of iodine levels in Chinese adults, especially in women of childbearing age.

Pregnane X receptor knockout mitigates weight gain and hepatic metabolic dysregulation in female C57BL/6 J mice on a long-term high-fat diet.

Obesity is a significant risk factor for several chronic diseases. However, pre-menopausal females are protected against high-fat diet (HFD)-induced obesity and its adverse effects. The pregnane X receptor (PXR, NR1I2), a xenobiotic-sensing nuclear receptor, promotes short-term obesity-associated liver disease only in male mice but not in females. Therefore, the current study investigated the metabolic and pathophysiological effects of a long-term 52-week HFD in female wild-type (WT) and PXR-KO mice and characterized the PXR-dependent molecular pathways involved. After 52 weeks of HFD ingestion, the body and liver weights and several markers of hepatotoxicity were significantly higher in WT mice than in their PXR-KO counterparts. The HFD-induced liver injury in WT female mice was also associated with upregulation of the hepatic mRNA levels of peroxisome proliferator-activated receptor gamma (Pparg), its target genes, fat-specific protein 27 (Fsp27), and the liver-specific Fsp27b involved in lipid accumulation, apoptosis, and inflammation. Notably, PXR-KO mice displayed elevated hepatic Cyp2a5 (anti-obesity gene), aldo-keto reductase 1b7 (Akr1b7), glutathione-S-transferase M3 (Gstm3) (antioxidant gene), and AMP-activated protein kinase (AMPK) levels, contributing to protection against long-term HFD-induced obesity and inflammation. RNA sequencing analysis revealed a general blunting of the transcriptomic response to HFD in PXR-KO compared to WT mice. Pathway enrichment analysis demonstrated enrichment by HFD for several pathways, including oxidative stress and redox pathway, cholesterol biosynthesis, and glycolysis/gluconeogenesis in WT but not PXR-KO mice. In conclusion, this study provides new insights into the molecular mechanisms by which PXR deficiency protects against long-term HFD-induced severe obesity and its adverse effects in female mice.

Flavonol profiles of mature leaves allow discriminating Toona sinensis Roem from different north-south geographical origins across China with varied antioxidant activities.

Toona sinensis (A. Juss.) Roem, a multipurpose economic tree, is widely cultivated across Asia, but its high-yielding mature leaves are largely overlooked. This study systematically analysed the flavonols in the mature leaves of T. sinensis from 44 different geographic locations across China, using HPLC-DAD and HPLC-ESI-MS2 techniques. In total, 18 flavonols were detected, among which 6 (f1, f3, f7, f14, f15, and f17) were firstly identified in this plant. Significant variations in quality among different T. sinensis varieties were observed (p < 0.01). Through OPLS-DA analysis, all samples could be clearly categorised into two distinct geographical groups. The northern varieties (N1-N20) exhibited concise flavonol fingerprints with higher total flavonol content (TFC) (727.55 ± 22.79 mg/100 g fresh weight, FW), predominantly non-acylated flavonols (705.95 ± 21.65 mg/100 g FW), particularly quercetin glycosides (614.60 ± 22.76 mg/100 g FW). In contrast, the southern varieties (S1-S24) presented more intricate flavonol profiles with lower TFC (622.81 ± 21.82 mg/100 g FW) and balanced amounts of quercetin (344.75 ± 16.41 mg/100 g FW) and kaempferol glycosides (278.06 ± 12.29 mg/100 g FW). Notably, the southern samples possessed higher content of acylated flavonols (184.50 ± 12.87 mg/100 g FW), especially galloylated ones, which contributed to their heightened antioxidant activities. Quercetin 3-O-rhamnoside (f11') and kaempferol 3-O-galloyglucoside (f11) were determined to be the crucial biomarkers for quality discrimination. Considering quality control of mature T. sinensis leaves as potential resources for natural flavonol extraction, this study suggested that their northern/southern geographic origins should be distinguished first. Additionally, the flavonol profiles allow for discriminating the origin and assessing the quality of T. sinensis.

The C4 photosynthesis bifunctional enzymes, PDRPs, of maize are co-opted to cytoplasmic viral replication complexes to promote infection of a prevalent potyvirus sugarcane mosaic virus.

In maize, two pyruvate orthophosphate dikinase (PPDK) regulatory proteins, ZmPDRP1 and ZmPDRP2, are respectively specific to the chloroplast of mesophyll cells (MCs) and bundle sheath cells (BSCs). Functionally, ZmPDRP1/2 catalyse both phosphorylation/inactivation and dephosphorylation/activation of ZmPPDK, which is implicated as a major rate-limiting enzyme in C4 photosynthesis of maize. Our study here showed that maize plants lacking ZmPDRP1 or silencing of ZmPDRP1/2 confer resistance to a prevalent potyvirus sugarcane mosaic virus (SCMV). We verified that the C-terminal domain (CTD) of ZmPDRP1 plays a key role in promoting viral infection while independent of enzyme activity. Intriguingly, ZmPDRP1 and ZmPDRP2 re-localize to cytoplasmic viral replication complexes (VRCs) following SCMV infection. We identified that SCMV-encoded cytoplasmic inclusions protein CI targets directly ZmPDRP1 or ZmPDRP2 or their CTDs, leading to their re-localization to cytoplasmic VRCs. Moreover, we found that CI could be degraded by the 26S proteasome system, while ZmPDRP1 and ZmPDRP2 could up-regulate the accumulation level of CI through their CTDs by a yet unknown mechanism. Most importantly, with genetic, cell biological and biochemical approaches, we provide evidence that BSCs-specific ZmPDRP2 could accumulate in MCs of Zmpdrp1 knockout (KO) lines, revealing a unique regulatory mechanism crossing different cell types to maintain balanced ZmPPDK phosphorylation, thereby to keep maize normal growth. Together, our findings uncover the genetic link of the two cell-specific maize PDRPs, both of which are co-opted to VRCs to promote viral protein accumulation for robust virus infection.

Seed-mediated growth synthesis and tunable narrow-band luminescence of quaternary Ag-In-Ga-S alloyed nanocrystals.

Silver-based I-III-VI-type semiconductor nanocrystals have received extensive attention due to their narrow-band luminescence properties. Herein, we demonstrated a seed-mediated growth of quaternary Ag-In-Ga-S (AIGS) nanocrystals (NCs) with narrow-band luminescence. By conducting partial cation exchange with In3+ and Ga3+ based on Ag2S NCs and controlling the Ag/In feeding ratios (0.25 to 2) of Ag-In-S seeds as well as the inventory of 1-dodecanethiol, we achieved optimized luminescence performance in the synthesized AIGS NCs, characterized by a narrow full width at half maximum of less than 40 nm. Meanwhile, narrow-band luminescent AIGS NCs exhibit a tetragonal AgGaS2 crystal structure and a gradient alloy structure, rather than a core-shell structure. Most importantly, the kinetics decay curves of time-resolved photoluminescence and the ground state bleaching in transient absorption generally agree with each other regarding the lifetime of the second decay component, which indicates that the narrow-band luminescence is due to the slow radiative recombination between trapped electrons and trapped holes located at the edge of the conduction band and the deep silver-related trap states (e.g., silver vacancy), respectively. This study provides new insights into the correlation between the narrow-band luminescence properties and the structural characteristics of AIGS NCs.

Low-frequency vibrational density of states of ordinary and ultra-stable glasses.

A remarkable feature of disordered solids distinct from crystals is the violation of the Debye scaling law of the low-frequency vibrational density of states. Because the low-frequency vibration is responsible for many properties of solids, it is crucial to elucidate it for disordered solids. Numerous recent studies have suggested power-law scalings of the low-frequency vibrational density of states, but the scaling exponent is currently under intensive debate. Here, by classifying disordered solids into stable and unstable ones, we find two distinct and robust scaling exponents for non-phononic modes at low frequencies. Using the competition of these two scalings, we clarify the variation of the scaling exponent and hence reconcile the debate. Via the study of both ordinary and ultra-stable glasses, our work reveals a comprehensive picture of the low-frequency vibration of disordered solids and sheds light on the low-frequency vibrational features of ultra-stable glasses on approaching the ideal glass.

Estrogen receptor-related receptor (Esrra) induces ribosomal protein Rplp1-mediated adaptive hepatic translation during prolonged starvation.

Protein translation is an energy-intensive ribosome-driven process that is reduced during nutrient scarcity to conserve cellular resources. During prolonged starvation, cells selectively translate specific proteins to enhance their survival (adaptive translation); however, this process is poorly understood. Accordingly, we analyzed protein translation and mRNA transcription by multiple methods in vitro and in vivo to investigate adaptive hepatic translation during starvation. While acute starvation suppressed protein translation in general, proteomic analysis showed that prolonged starvation selectively induced translation of lysosome and autolysosome proteins. Significantly, the expression of the orphan nuclear receptor, estrogen-related receptor alpha (Esrra) increased during prolonged starvation and served as a master regulator of this adaptive translation by transcriptionally stimulating 60S acidic ribosomal protein P1 (Rplp1) gene expression. Overexpression or siRNA knockdown of Esrra expression in vitro or in vivo led to parallel changes in Rplp1 gene expression, lysosome/autophagy protein translation, and autophagy. Remarkably, we have found that Esrra had dual functions by not only regulating transcription but also controling adaptive translation via the Esrra/Rplp1/lysosome/autophagy pathway during prolonged starvation.

Understanding the glassy dynamics from melting temperatures in binary glass-forming liquids.

It is natural to expect that small particles in binary mixtures move faster than large ones. However, in binary glass-forming liquids with soft-core particle interactions, we observe the counterintuitive dynamic reversal between large and small particles along with the increase of pressure by performing molecular dynamics simulations. The structural relaxation (dynamic heterogeneity) of small particles is faster (weaker) than large ones at low pressures, but becomes slower (stronger) above a crossover pressure. In contrast, this dynamic reversal never happens in glass-forming liquids with hard-core interactions. We find that the difference of the effective melting temperatures felt by large and small particles can be used to understand the dynamic reversal. In binary mixtures, we derive effective melting temperatures of large and small particles simply from the conversion of units and find that particles with a higher effective melting temperature usually undergo a slower and more heterogeneous relaxation. The presence (absence) of the dynamic reversal in soft-core (hard-core) systems is simply due to the non-monotonic (monotonic) behavior of the melting temperature as a function of pressure. Interestingly, by manipulating the relative softness between large and small particles, we obtain a special case of soft-core systems, in which large particles always have higher effective melting temperatures than small ones. As a result, the dynamic reversal is totally eliminated. Our work provides another piece of evidence of the underlying connections between the properties of non-equilibrium glass-formers and equilibrium crystal-formers.

Predictive role of impulsivity, anxiety, and depression in the efficacy of intermittent theta burst transcranial magnetic stimulation modalities for treating methamphetamine use disorder: A randomized clinical trial.

INTRODUCTION: Methamphetamine use disorder (MUD) can cause impulsive behavior, anxiety, and depression. Stimulation of the left dorsolateral prefrontal cortex in MUD patients by intermittent theta burst repetitive transcranial magnetic stimulation (iTBS-rTMS) is effective in reducing cravings, impulsive behavior, anxiety, and depression. The purpose of this study was to explore whether these psychological factors helped to predict MUD patients' responses to iTBS-rTMS treatment. METHODS: Fifty MUD patients and sixty healthy subjects matched for general conditions were used as study subjects. The study randomly divided MUD patients into iTBS-rTMS and sham stimulation groups and received 20 sessions of real or sham iTBS-rTMS treatment, and the study collected cue-related evoked craving data before and after treatment. All subjects completed the Barratt Impulsiveness Scale (BIS-11), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS). RESULTS: The MUD patients showed significantly higher levels of impulsivity, anxiety, and depression than the healthy subjects. The MUD patients who received the real treatment had significantly lower impulsivity, anxiety, and depression scores, and better treatment effects on cravings than the sham stimulation group. The Spearman rank correlation and stepwise multiple regression analyses showed that the baseline BIS-11 and the reduction rate (RR) of BIS-11 and RR of SDS were positively correlated with the decrease in cravings in the iTBS-rTMS group. ROC curve analysis showed that RR of SDS (AUC = 91.6 %; 95 % CI = 0.804-1.000) had predictive power to iTBS- rTMS therapeutic efficacy, the cutoff value is 15.102 %. CONCLUSIONS: iTBS-rTMS had a good therapeutic effect in MUD patients and the baseline impulsivity, the improved depression and impulsivity were associated with therapeutic effect of iTBS-rTMS. The improved depression had the potential to predict the efficacy of the iTBS-rTMS modality for MUD treatment.

Boosting Cu─In─Zn─S-based Quantum-Dot Light-Emitting Diodes Enabled by Engineering Cu─NiOx /PEDOT:PSS Bilayered Hole-Injection Layer.

The imbalance of charge injection is considered to be a major factor that limits the device performance of cadmium-free quantum-dot light-emitting diodes (QLEDs). In this work, high-performance cadmium-free Cu─In─Zn─S(CIZS)-based QLEDs are designed and fabricated through tailoring interfacial energy level alignment and improving the balance of charge injection. This is achieved by introducing a bilayered hole-injection layer (HIL) of Cu-doped NiOx (Cu─NiOx )/Poly(3,4-ethylenedioxythiophene): poly (styrene sulfonate) (PEDOT:PSS). High-quality Cu─NiOx film is prepared through a novel and straightforward sol-gel procedure. Multiple experimental characterizations and theoretical calculations show that the incorporation of Cu2+ ions can regulate the energy level structure of NiOx and enhance the hole mobility. The state-of-art CIZS-based QLEDs with Cu─NiOx /PEDOT:PSS bilayered HIL exhibit the maximum external quantum efficiency of 6.04% and half-life time of 48 min, which is 1.3 times and four times of the device with only PEDOT:PSS HIL. The work provides a new pathway for developing high-performance cadmium-free QLEDs.

Effects of Online Game and Short Video Behavior on Academic Delay of Gratification - Mediating Effects of Anxiety, Depression and Retrospective Memory.

Objective: Learner dependence on short videos has many pitfalls for learning outcomes, but the negative effects of excessive short video use have been little discussed in the learning psychology literature. Therefore, this study investigated the effects of excessive short video use on anxiety, depression, prospective memory, and academically delayed gratification (ADOG) in relation to online gaming-related behaviours, and explored the possible mechanisms by which excessive online gaming and short video use may lead to decreased ADOG, to expand our understanding of excessive short video use. Methods: Based on the whole class random sampling method, a questionnaire survey was conducted among college students in Northern Anhui, China from May 7 to July 27, 2022. The questionnaires included the Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire Scale (PHQ-9), Prospective and Retrospective Memory (PRM) Questionnaire, and ADOG Scale. Results: A total of 1016 participants completed the survey. The study found that of all the internet behaviors, 20.8% of the college students mainly played online games, 43.9% mainly played short videos, and 35.3% conducted other online behaviors. When compared with other internet behaviors, online gaming and short video behaviors can cause more serious anxiety/depression and worse PRM and ADOG scores. As time spent playing online games and short videos increased, anxiety and depression became worse, and the scores for PRM and ADOG also declined. Anxiety, depression, and PRM mediate the relationship between time spent on online gaming/short videos and ADOG. Conclusion: Excessive short videos behaviour may produce the same psychological problems and learning problems as online gaming disorder. Excessive short video and online gaming behaviors may affect ADOG performance through anxiety, depression, and prospective memory. These findings could be used as a basis for future studies on the improvement of ADOG.

Characterization of the odor compounds in human milk by DHS/GC × GC-O-MS: A feasible and efficient method.

Odor analysis of human milk (HM) is often challenging. Here, a new strategy for the analysis of odorants in HM using dynamic headspace sampling combined with comprehensive two-dimensional gas chromatography-olfactometry-mass spectrometry (DHS/GC × GC-O-MS) was established based on the comparison of different extraction methods and instrument modes. Overall, DHS/GC × GC-O-MS was proved to be able to provide higher extraction efficiency and better analytical results of the odor-active compounds (OACs) in HM, meanwhile, the salt addition during the extraction further promoted the release of the odorants. Twenty key OACs in HM were identified by flavor dilution analysis and odor activity calculation, of which 1-octen-3-one, 2,3-butanedione, (E)-2-nonenal, and nonanal contributed significantly to the odor of HM. In addition, 2,3-pentanedione was detected as a key OAC in HM for the first time. This study provided a powerful analytical strategy for the comprehensive odor analysis of HM.

Betacoronaviruses SARS-CoV-2 and HCoV-OC43 infections in IGROV-1 cell line require aryl hydrocarbon receptor.

The emergence of novel betacoronaviruses has posed significant financial and human health burdens, necessitating the development of appropriate tools to combat future outbreaks. In this study, we have characterized a human cell line, IGROV-1, as a robust tool to detect, propagate, and titrate betacoronaviruses SARS-CoV-2 and HCoV-OC43. IGROV-1 cells can be used for serological assays, antiviral drug testing, and isolating SARS-CoV-2 variants from patient samples. Using time-course transcriptomics, we confirmed that IGROV-1 cells exhibit a robust innate immune response upon SARS-CoV-2 infection, recapitulating the response previously observed in primary human nasal epithelial cells. We performed genome-wide CRISPR knockout genetic screens in IGROV-1 cells and identified Aryl hydrocarbon receptor (AHR) as a critical host dependency factor for both SARS-CoV-2 and HCoV-OC43. Using DiMNF, a small molecule inhibitor of AHR, we observed that the drug selectively inhibits HCoV-OC43 infection but not SARS-CoV-2. Transcriptomic analysis in primary normal human bronchial epithelial cells revealed that DiMNF blocks HCoV-OC43 infection via basal activation of innate immune responses. Our findings highlight the potential of IGROV-1 cells as a valuable diagnostic and research tool to combat betacoronavirus diseases.

Characterization of key aroma-active compounds in blue honeysuckle (Lonicera caerulea L.) berries by sensory-directed analysis.

Blue honeysuckle (Lonicera caerulea L.) berries are nutritionally rich and unique in flavor. However, its aroma compounds have not been known well. In this study, the key aroma-active compounds in 8 different varieties of blue honeysuckle berries were studied by sensory-directed analysis. Sensory evaluation suggested that the aroma profile of blue honeysuckle berry was fruity, floral, grassy, sweet, and sour. A total of 68 aroma compounds were detected by two-dimensional comprehensive gas chromatography-olfactometry-mass spectrometry analysis (GC × GC-O-MS). Then, aroma extraction dilution analysis (AEDA) and odor activity value (OAV) showed that 12 compounds were indicated to be the major aroma contributors. According to the principal component analysis (PCA) results, eight varieties were divided into three categories for their differences on alcohols and terpenoids content. Finally, the aroma recombination and omission experiments determined that linalool, hexanal, eucalyptol, octanal, nonanal, and ethyl 2-methylbutyrate were the key aroma-active compounds in blue honeysuckle berries.

Odor changes in breast milk during different storage temperatures and times using GC × GC-O-MS.

Breastfeeding is generally the preferred way that most mothers will choose. It is common to store expressed breast milk in the refrigerator in many families. However, there is a phenomenon that infants may refuse to consume stored breast milk, presumably due to changes in odor. Thus, the odor changes in breast milk stored at 4 °C for 72 h and at -20 °C for 60 d were studied. Compared with fresh breast milk, 7 and 16 odor compounds were newly detected by SPME and GC × GC-O-MS when breast milk was stored at 4 and -20 °C, respectively. The concentration of (E)-2-decenal, octanal, hexanal, 1-octen-3-ol, 2-pentylfuran, lauric acid, decanoic acid and hexanoic acid significantly increased after storage at 4 °C for 36 h and -20 °C for 30 d. In addition, the proportion of acids increased, whereas that of aldehydes decreased during storage. Chemometric analysis with OPLS-DA suggested that breast milk should be stored at 4 °C for less than 36 h and at -20 °C for less than 30 d for maximum preservation of the original odors.

Scaling of the non-phononic spectrum of two-dimensional glasses.

Low-frequency vibrational harmonic modes of glasses are frequently used to rationalize their universal low-temperature properties. One well studied feature is the excess low-frequency density of states over the Debye model prediction. Here, we examine the system size dependence of the density of states for two-dimensional glasses. For systems of fewer than 100 particles, the density of states scales with the system size as if all the modes were plane-wave-like. However, for systems greater than 100 particles, we find a different system-size scaling of the cumulative density of states below the first transverse sound mode frequency, which can be derived from the assumption that these modes are quasi-localized. Moreover, for systems greater than 100 particles, we find that the cumulative density of states scales with the frequency as a power law with the exponent that leads to the exponent ß = 3.5 for the density of states. For systems whose sizes were investigated, we do not see a size-dependence of exponent ß.

Novel application of drug-coated balloons in coronary heart disease: A narrative review.

The incidence of coronary heart disease (CAD) has soared over the years, and coronary intervention has become an increasingly important therapeutic approach. The past decade has witnessed unprecedented developments in therapeutic medical instruments. Given that drug-coated balloons bring many benefits, they are indicated for an increasing number of conditions. In this article, we review the results of current clinical trials about drug-coated balloons and summarize their safety and clinical progression in different coronary artery diseases, laying the groundwork for basic research, and clinical therapeutics of this patient population.

Interactome Analysis of Visceral Adipose Tissue Elucidates Gene Regulatory Networks and Novel Gene Candidates in Obesity.

Objective: Visceral adiposity is associated with increased proinflammatory activity, insulin resistance, diabetes risk and mortality rate. Numerous individual genes have been associated with obesity, but studies investigating gene-regulatory networks in human visceral obesity are lacking. Methods: We analyzed gene-regulatory networks in human visceral adipose tissue (VAT) from 48 obese and 11 non-obese Chinese subjects using gene co-expression and network construction with RNA-sequencing data. We also conducted RNA interference-based tests on selected genes for adipocyte differentiation effects. Results: A scale-free gene co-expression network was constructed from 360 differentially expressed genes between obese and non-obese VAT (absolute log fold-change >1, FDR<0.05) with edge probability >0.8. Gene regulatory network analysis identified candidate transcription factors associated with differentially expressed genes. Fifteen subnetworks (communities) displayed altered connectivity patterns between obese and non-obese networks. Genes in pro-inflammatory pathways showed increased network connectivities in obese VAT whereas the oxidative phosphorylation pathway displayed reduced connections (enrichment FDR<0.05). Functional screening via RNA interference identified SOX30 and OSBPL3 as potential network-derived gene candidates influencing adipocyte differentiation. Conclusions: This interactome-based approach highlights the network architecture, identifies novel candidate genes, and leads to new hypotheses regarding network-assisted gene regulation in obese vs. non-obese VAT.What is already known about this subject?: Visceral adipose tissue (VAT) is associated with increased levels of proinflammatory activity, insulin resistance, diabetes risk and mortality rate.Gene expression studies have identified candidate genes associated with proinflammatory function in VAT.What are the new findings in your manuscript?: Using integrative network-science, we identified co-expression and gene regulatory networks that are differentially regulated in VAT samples from subjects with and without obesityWe used functional testing (adipocyte differentiation) to validate a subset of novel candidate genes with minimal prior reported associations to obesityHow might your results change the direction of research or the focus of clinical practice: Network biology-based investigation provides a new avenue to our understanding of gene function in visceral adiposityFunctional validation screen allows for the identification of novel gene candidates that may be targeted for the treatment of adipose tissue dysfunction in obesity.