Dihydroartemisinin breaks the positive feedback loop of YAP1 and GLUT1-mediated aerobic glycolysis to boost the CD8+ effector T cells in hepatocellular carcinoma.

Aerobic glycolysis is a hallmark of hepatocellular carcinoma (HCC). Dihydroartemisinin (DHA) exhibits antitumor activity towards liver cancer. Our previous studies have shown that DHA inhibits the Warburg effect in HCC cells. However, the mechanism still needs to be clarified. Our study aimed to elucidate the interaction between YAP1 and GLUT1-mediated aerobic glycolysis in HCC cells and focused on the underlying mechanisms of DHA inhibiting aerobic glycolysis in HCC cells. In this study, we confirmed that inhibition of YAP1 expression lowers GLUT1-mediated aerobic glycolysis in HCC cells and enhances the activity of CD8+T cells in the tumor niche. Then, we found that DHA was bound to cellular YAP1 in HCC cells. YAP1 knockdown inhibited GLUT1-mediated aerobic glycolysis, whereas YAP1 overexpression promoted GLUT1-mediated aerobic glycolysis in HCC cells. Notably, liver-specific Yap1 knockout by AAV8-TBG-Cre suppressed HIF-1α and GLUT1 expression in tumors but not para-tumors in DEN/TCPOBOP-induced HCC mice. Even more crucial is that YAP1 forms a positive feedback loop with GLUT1-mediated aerobic glycolysis, which is associated with HIF-1α in HCC cells. Finally, DHA reduced GLUT1-aerobic glycolysis in HCC cells through YAP1 and prevented the binding of YAP1 and HIF-1α. Collectively, our study revealed the mechanism of DHA inhibiting glycolysis in HCC cells from a perspective of a positive feedback loop involving YAP1 and GLUT1 mediated-aerobic glycolysis and provided a feasible therapeutic strategy for targeting enhanced aerobic glycolysis in HCC.

Lycium barbarum L. Balanced intestinal flora with YAP1/FXR activation in drug-induced liver injury.

Drug-induced liver injury (DILI) is a common and severe adverse drug reaction that can result in acute liver failure. Previously, we have shown that Lycium barbarum L. (wolfberry) ameliorated liver damage in acetaminophen (APAP)-induced DILI. Nevertheless, the mechanism needs further clarification. Herein, we utilized APAP-induced DILI mice to investigate how wolfberry impacts the gut-liver axis to mitigate liver damage. We showed that the abundance of Akkermansia muciniphila (A. muciniphila) was decreased, and intestinal microbiota was disrupted, while the expression levels of YAP1 and FXR-mediated CYP7A1 were reduced in the liver of DILI mice. Furthermore, wolfberry increased the abundance of A. muciniphila and the number of goblet cells in the intestines, while decreasing AST, ALT, and total bile acids (TBA) levels in the serum. Interestingly, A. muciniphila promoted YAP1 and FXR expression in hepatocytes, leading to the inhibition of CYP7A1 expression and a decrease in TBA content. Notably, wolfberry did not exert the beneficial effects mentioned above after the removal of intestinal bacteria by antibiotics (ATB)-containing water. Additionally, Yap1 knockout downregulated FXR expression and enhanced CYP7A1 expression in the liver of hepatocyte-specific Yap1 knockout mice. Therefore, wolfberry stimulated YAP1/FXR activation and reduced CYP7A1 expression by promoting the balance of intestinal microbiota, thereby suppressing the overproduction of bile acids.

A highly efficient process to enhance the bioleaching of spent lithium-ion batteries by bifunctional pyrite combined with elemental sulfur.

Bioleaching technologies have been shown to be an environmentally friendly and economically beneficial tool for extracting metals from spent lithium-ion batteries (LIBs). However, conventional bioleaching methods have exhibited low efficiency in recovering metals from spent LIBs. Therefore, relied on the sustainability principle of using waste to treat waste, this study employed pyrite (FeS2) as an energy substance with reducing properties and investigated its effects in combination with elemental sulfur (S0) or FeSO4 on metals bioleaching from spent LIBs. Results demonstrated that the bioleaching efficiency was significantly higher in the leaching system constructed with FeS2 + S0, than in the FeS2 + FeSO4 or FeS2 system. When the pulp densities of FeS2, S0 and spent LIBs were 10 g L-1, 5 g L-1 and 10 g L-1, respectively, the leaching efficiency of Li, Ni, Co and Mn all reached 100%. Mechanistic analysis reveals that in the FeS2 + S0 system, the activity and acid-producing capabilities of iron-sulfur oxidizing bacteria were enhanced, promoting the generation of Fe (Ⅱ) and reducible sulfur compounds. Simultaneously, bio-acids were shown to disrupt the structure of the LIBs, thereby increasing the contact area between Fe (Ⅱ) and sulfur compounds containing high-valence metals. This effectively promoted the reduction of high-valence metals, thereby enhancing their leaching efficiency. Overall, the FeS2 + S0 bioleaching process constructed in this study, improved the leaching efficiency of LIBs while also effectively utilizing waste, providing technical support for the comprehensive and sustainable management of solid waste.

Wolfberry, Yam, and Chrysanthemum polysaccharides increased intestinal Akkermansia muciniphila abundance and hepatic YAP1 expression to alleviate DILI.

Drug-induced liver injury (DILI) is frequently induced by high dose of acetaminophen (APAP) and is concomitant with disturbances of gut flora. Akkermansia muciniphila is beneficial for the repair of liver injury. Lycium barbarum polysaccharide, yam polysaccharide, and chrysanthemum polysaccharide all have anti-inflammatory and antioxidation effects. The objective of this study is to investigate the potential of lycium barbarum polysaccharide, yam polysaccharide, and chrysanthemum polysaccharide (LYC) in improving DILI by increasing the abundance of A. muciniphila. Initially, screening for the optimal concentrations of wolfberry, yam, and chrysanthemum (WYC) or LYC to promote A. muciniphila proliferation in vitro and validated in antibiotic (ATB)-treated KM mice. Subsequently, APAP-induced DILI model in BALB/c mice were constructed to examine the treatment effects of LYC. Our findings indicate that the optimal concentration ratio of WYC was 2:3:2, and LYC was 1:1:1. WYC increased A. muciniphila proliferation in vitro and in ATB-treated mice under this ratio. Meanwhile, LYC increased A. muciniphila abundance in vitro and the combination LYC with A. muciniphila promoted the proliferation of A. muciniphila in ATB-treated mice. The overdose of APAP resulted in the impairment of the intestinal barrier function and subsequent leakage of lipopolysaccharide (LPS). Moreover, LYC increased A. muciniphila abundance, reduced intestinal inflammation and permeability, and upregulated the expression of the tight junction protein zonula occludens protein 1 (ZO-1) and occludin contents in the gut. Lastly, LYC inhibited LPS leakage and upregulated hepatic YAP1 expression, ultimately leading to the repair of DILI.

RcSPL1-RcTAF15b regulates the flowering time of rose (Rosa chinensis).

Rose (Rosa chinensis), which is an economically valuable floral species worldwide, has three types, namely once-flowering (OF), occasional or re-blooming (OR), and recurrent or continuous flowering (CF). However, the mechanism underlying the effect of the age pathway on the duration of the CF or OF juvenile phase is largely unknown. In this study, we observed that the RcSPL1 transcript levels were substantially upregulated during the floral development period in CF and OF plants. Additionally, accumulation of RcSPL1 protein was controlled by rch-miR156. The ectopic expression of RcSPL1 in Arabidopsis thaliana accelerated the vegetative phase transition and flowering. Furthermore, the transient overexpression of RcSPL1 in rose plants accelerated flowering, whereas silencing of RcSPL1 had the opposite phenotype. Accordingly, the transcription levels of floral meristem identity genes (APETALA1, FRUITFULL, and LEAFY) were significantly affected by the changes in RcSPL1 expression. RcTAF15b protein, which is an autonomous pathway protein, was revealed to interact with RcSPL1. The silencing and overexpression of RcTAF15b in rose plants led to delayed and accelerated flowering, respectively. Collectively, the study findings imply that RcSPL1-RcTAF15b modulates the flowering time of rose plants.

Hierarchical 3D Porous Hydrogen-Substituted Graphdiyne for High-Performance Electrochemical Lithium-Ion Storage.

Graphdiyne (GDY) has realized significant achievements in lithium-ion batteries (LIBs) because of its unique π-conjugated skeleton with sp- and sp2-hybridized carbon atoms. Enriching the accessible surface areas and diffusion pathways of Li ions can realize more storage sites and rapid transport dynamics. Herein, three-dimensional porous hydrogen-substituted GDY (HsGDY) is developed for high-performance Li-ion storage. HsGDY, fabricated via a versatile interface-assisted synthesis strategy, exhibits a large specific surface area (667.9 m2 g-1), a hierarchical porous structure, and an expanded interlayer space, which accelerate Li-ion accessibility and lithiation/delithiation. Owing to this high π-conjugated, conductive, and porous framework, HsGDY exhibits a large reversible capacity (930 mA h g-1 after 100 cycles at 1 A g-1), superior cycle (720 mA h g-1 after 300 cycles at 1 A g-1), and rate (490 mA h g-1 at 5 A g-1) performances. Density functional theory calculations of the low diffusion barrier in the lamination and vertical directions further reveal the fast Li-ion transport kinetics of HsGDY. Additionally, a LiCoO2-HsGDY full cell is constructed, which exhibits a good practical charge/discharge capacity of 128 mA h g-1 and stable cycling behavior. This study highlights the advanced design of next-generation LIBs to sustainably develop the new energy industry.

Dihydroartemisinin inhibited interleukin-18 expression by decreasing YAP1 in hepatocellular carcinoma cells.

BACKGROUND: Yes-associated protein 1 (YAP1) is highly expressed in liver cancer and has been used as an independent prognostic marker for hepatocellular carcinoma (HCC), while inhibition of YAP1 slows down the progression of HCC. Interleukin-18 (IL-18) also tends to be highly expressed in liver cancer. Previous research has proved that dihydroartemisinin (DHA) plays an important role in HCC treatment by reducing YAP1 expression. However, the relationship between YAP1 and IL-18 has not been reported in HCC, especially during DHA therapy. OBJECTIVE: The purpose of this study was to clarify the relationship between YAP1 and IL-18 in HCC cells, and to explicit the role of IL-18 in the treatment of HCC by DHA. METHODS AND RESULTS: We found that YAP1 and IL-18 were highly expressed in patients with hepatocellular carcinoma by bioinformatics analysis. Moreover, YAP1 was positively correlated with IL18 in liver cancer. YAP1 and IL18 correlated with immune cell infiltration, notably T cell exhaustion. YAP1 knockdown decreased IL-18 expression, while YAP1 overexpression increased the IL-18 expression in HCC cells. DHA reduced IL-18 expression through YAP1 in HCC cells. Further, DHA reduced the growth of Hepa1-6 cells subcutaneous xenograft tumors by inhibiting the expression of YAP1 and IL-18. However, DHA improved IL-18 in serum and adjacent tissues from DEN/TCPOBOP-induced liver tumor model in C57BL/6 mice. CONCLUSION: YAP1 was positively correlated with IL-18 in HCC. DHA reduced the expression of IL-18 by inhibiting YAP1 and plays a role in the treatment of HCC. Our study suggested that IL-18 is a potential target for the treatment of HCC, and DHA is a promising drug for HCC therapy. DATA AVAILABILITY: The dataset that supports the findings of this study is available from the corresponding author upon reasonable request.

The collective vibrational modes of dihydropyridine in nifedipine studied by terahertz spectroscopy.

Cardiovascular pharmaceuticals have drawn huge attention in drug development. Nifedipine (NFD) is an important member of calcium channel blockers (CCB) with the structural characteristic of dihydropyridine (DHP), but the binding mechanism to its target remains an open question. Even though several analytical techniques have been used for structural characterizations, the information of collective vibrational behavior is still lacking. In this work, we use terahertz (THz) spectroscopy to investigate the spectral fingerprints of NFD, and quantitatively evaluate the temperature-induced frequency shifts. Combined with quantum chemical calculations, each THz fingerprint is attributed to specific collective vibrational modes. The collective vibrations of DHP are mainly distributed below 2.5 THz, which provides complementary information to understand the behavior of rigid DHP ring. The rotation of methyl group and the wagging of nitrophenyl group are widely distributed in the range of 1.0-4.0 THz, which is helpful for the conformational recognition between NFD and target molecule. THz spectroscopy is demonstrated to be suitable for characterizing the collective vibrational modes of DHP and elucidating the drug-target binding behavior from the perspective of noncovalent interactions. It has the potential to become a non-invasive technology for conformational analysis and pharmaceutical development.

YAP1 suppression inhibits autophagy and improves the efficacy of anti-PD-1 immunotherapy in hepatocellular carcinoma.

Anti-PD-1 immunotherapy is a promising treatment for hepatocellular carcinoma (HCC), but some patients with HCC do not experience clinical benefits. Autophagy promotes tumor progression and participates in drug resistance. Previous studies have revealed that suppressing the expression level of Yes-associated protein 1 (YAP1) improves anti-PD-1 therapy efficacy. Therefore, the relationship between YAP1 expression and autophagy activity during anti-PD-1 treatment was investigated in this study. A positive correlation was found between the expression level of YAP1 and LC3B by analyzing The Cancer Genome Atlas (TCGA), UALCAN databases, and HCC tissue microarray. Meanwhile, YAP1 expression and autophagy constituted positive feedback, in which YAP1 inhibition decreased the autophagy activity in liver tumor cells by hepatocyte-specific Yap1 knockout mice. Further, anti-PD-1 treatment increased autophagy and YAP1 expression levels in the cancer tissues from DEN/TCPOBOP-induced liver cancer mice. Finally, Yap1 knockout suppressed autophagy and improved anti-PD-1 therapy efficacy in hepatocyte-specific Yap1 knockout mice with liver tumors. These results suggested that YAP1 suppression was sensitized to anti-PD-1 treatment and inhibited autophagy activity in liver tumor cells. YAP1 is a promising target for improving the efficacy of anti-PD-1 immunotherapy in HCC.

Wolfberry enhanced the abundance of Akkermansia muciniphila by YAP1 in mice with acetaminophen-induced liver injury.

Drug-induced liver injury (DILI) by acetaminophen (APAP) was one of the most challenging liver diseases. Wolfberry (Lycium barbarum L.), a traditional Chinese medicinal material and food supplement, has a potential effect on increasing the abundance of Akkermansia muciniphila (A. muciniphila) in mice colons. However, the effect and mechanism of wolfberry remain unclear in APAP-induced DILI. In this study, wolfberry promoted the proliferation of activated-A. muciniphila in vitro and in vivo. For the first time, we detected that the activated-A. muciniphila but not the killed-A. muciniphila increased the expression level of Yes-associated protein 1 (YAP1) in the liver and alleviated liver injury in APAP-induced DILI mice. Mechanically, A. muciniphila improved the intestinal mucosal barrier and reduced lipopolysaccharide (LPS) content in the liver, leading to the increased expression level of YAP1. Furthermore, wolfberry increased the A. muciniphila abundance in the colon and YAP1 expression in the liver from APAP-induced DILI mice, which promoted the recovery of APAP-induced liver injury. Meanwhile, wolfberry combination with A. muciniphila synergistically increased AKK abundance and YAP1 expression in the liver. Our research provides an innovative strategy to improve DILI.

Constitutive androstane receptor (CAR) mediates pyrene-induced inflammatory responses in mouse liver, with increased serum amyloid A proteins and Th17 cells.

BACKGROUND AND PURPOSE: The constitutive androstane receptor (CAR), a known xenobiotic sensor, plays an important role in drug metabolism by regulating numerous genes. The polycyclic aromatic hydrocarbon pyrene, an environmental pollutant, is a CAR activator and induces mouse hepatotoxicity via CAR. Here, we investigate the molecular mechanisms of the inflammatory response in pyrene-caused mice liver injury. EXPERIMENTAL APPROACH: Effects of pyrene on the liver were investigated in wild-type and CAR knockout (KO) mice. Levels of pyrene and its urinary metabolite were analysed by high performance liquid chromatography (HPLC). Inflammatory responses were measured by qRT-PCR, western blotting, and ELISA for cytokines. KEY RESULTS: Serum amyloid A proteins (SAAs) were markedly increased in the liver and serum of pyrene-exposed wild-type mice. IL-17-producing helper T cells (Th17 cells) and IL-17 levels were increased in the liver of pyrene-exposed wild-type mice. Hepatic mRNA levels of inflammatory cytokines including IL-1ß, IL-6 and TNFα, and serum IL-6 levels were significantly elevated in pyrene-treated wild-type mice. However, these changes were not observed in CAR KO mice. CONCLUSION AND IMPLICATIONS: CAR plays a crucial role in pyrene-caused mice liver inflammatory response with increased SAAs and Th17 cells. Our results suggest that serum SAAs may be a convenient biomarker for early diagnosis of liver inflammatory response caused by polycyclic aromatic hydrocarbons, including pyrene. CAR and Th17 cells may be potential targets for novel therapeutic strategies for xenobiotic-induced liver inflammation.

The fingerprints of nifedipine/isonicotinamide cocrystal polymorph studied by terahertz time-domain spectroscopy.

Cocrystal is constructed to improve physicochemical properties of active pharmaceutical ingredient and prevent polymorphism via intermolecular interactions. However, recent examples on cocrystal polymorphs display significantly different properties. Even though some analytical techniques have been used to characterize the cocrystal polymorphic system, it remains unclear how intermolecular interactions drive and stabilize the structure. In this work, we study the cocrystal polymorphs of nifedipine (NFD) and isonicotinamide (INA) using terahertz (THz) spectroscopy. Form I and form II of NFD-INA cocrystals show spectral fingerprints in THz region. Temperature-dependent THz spectra display distinguished frequency shifts of each fingerprint. Combined with solid-state density functional theory (DFT) calculations, the experimental fingerprints and their distinct responses to temperature are elucidated by specific collective vibrational modes. The vibrations of hydrogen bonding between dihydropyridine ring of NFD and INA are generally distributed below 1.5 THz, which play important roles in stabilizing cocrystal and preventing the oxidation of NFD. The rotations of methyl group in NFD are widely distributed in the range of 1.5-4.0 THz, which helps the steric recognition. The results demonstrate that THz spectroscopy is a sensitive tool to discriminate cocrystal polymorphs. It has the potential to be used as a non-invasive technique for pharmaceutical screening.

H2O2-Responsive prodrug-nanosystem based on auto-fluorescent perylenetetracarboxylic diimide hinders the foaming progress in RAW264.7 cells.

Oxidative stress can lead to a variety of diseases, and oxalate bonds can consume excess reactive oxygen species (ROS) in cells. In this study, a H2O2-responsive prodrug-nanosystem was synthesized using oxalate-bond-connecting water-soluble drugs (Tre) with a fluorescent indicator (PBI). The maximum fluorescence emission wavelength of PBI-Tre was at 548 nm, and the changes of nanoparticles could be directly observed in the cells. PBI-Tre was coated with hyaluronic acid (HA) to improve their intracellular uptake and ability to target macrophages. The particle size of HA-PBI-Tre was 200-300 nm, and the zeta potential was -36.9 mV. The results showed that the nano-drug loading system could easily decrease the ROS level, inhibit the production of inflammatory factors, remove the accumulation of lipids in foam cells. These nanoparticles could hinder foaming progress in the RAW264. 7 cell line.

GrpE is involved in mitochondrial function and is an effective target for RNAi-mediated pest and arbovirus control.

Laodelphax striatellus is a sap-feeding pest and the main insect vector of rice stripe virus (RSV). There is an urgent need to identify molecular targets to control this insect pest and plant arboviruses. In this study, we identified a L. striatellus gene (named LsGrpE) encoding a GroP-E-like protein. We found that the LsGrpE protein localized to mitochondria. Using gene-specific dsRNA to interfere with the expression of LsGrpE led to a significant increase in insect mortality, and most of the surviving insects could not develop into adults. Further analyses revealed that LsGrpE deficiency caused mitochondrial dysfunction and inhibited the insulin pathway, resulting in diabetes-like symptoms such as elevated blood sugar, inactive behaviour, developmental delay, and death. In addition, LsGrpE deficiency significantly reduced the RSV titre in surviving L. striatellus, and indirectly prevented viral vertical transmission by reducing the number of adults. We generated transgenic rice plants expressing LsGrpE-specific dsRNA, and the dsRNA was acquired by L. striatellus during feeding, resulting in increased insect mortality and the prevention of arboviral transmission. This study clarifies the function of LsGrpE and demonstrates that LsGrpE can be used as a molecular target of plant-generated dsRNA to resist this sap-feeding pest, a17nd therefore, its transmitted arboviruses.

Microfluidic Fabrication of Hierarchical-Ordered ZIF-L(Zn)@Ti3 C2 Tx Core-Sheath Fibers for High-Performance Asymmetric Supercapacitors.

We report hierarchical-ordered ZIF-L(Zn)@Ti3 C2 Tx MXene core-sheath fibers, in which a ZIF-L(Zn) nanowall array sheath is grown vertically on an anisotropic Ti3 C2 Tx core by Ti-O-Zn/Ti-F-Zn chemical bonds. Through highly efficient microfluidic assembly and microchannel reactions, ZIF-L(Zn)@Ti3 C2 Tx exhibits well-developed micro-/mesoporosity, ordered ionic pathways, fast interfacial electron conduction and large-scale fabrication, significantly boosting charges dynamic transport and intercalation. The resultant ZIF-L(Zn)@Ti3 C2 Tx fiber presents large capacitance (1700 F cm-3 ) and outstanding rate performance in a 1 M H2 SO4 electrolyte. Additionally, ZIF-L(Zn)@Ti3 C2 Tx fiber-based solid-state asymmetric supercapacitors deliver high energy density (19.0 mWh cm-3 ), excellent capacitance (854 F cm-3 ), large deformable/wearable capabilities and long-time cyclic stability (20 000 cycles), which realize natural sunlight-induced self-powered applications to drive water level/earthquake alarm devices.

Gaming Motivation and Negative Psychosocial Outcomes in Male Adolescents: An Individual-Centered 1-Year Longitudinal Study.

"Gaming motivation" is a useful concept to draw upon when considering inconsistencies in the effects of online gaming on psychosocial wellbeing. However, most prior studies that utilize it are cross-sectional and do not allow that individuals can be driven by multiple motives. The present study uses an individual-centered method to classify gaming motivation styles of male adolescents and longitudinally observes the relationship between gaming motivations and psychosocial outcomes. A total of 929 healthy, male, adolescent gamers were recruited in October 2019 and classified into "recreational" "achiever," and "escaper" categories according to their baseline gaming motivations and self-esteem levels. Then, 1-year incidence rates of players and relative risks (RRs) of social withdrawal problems, anxiety/depression syndrome, and self-destructive/identity problems were assessed. Recreational players were found to have the lowest incidence of all the three psychosocial problems among the three categories, achievers only had a moderate risk of social withdrawal, compared to recreational players, while escapers showed a strong risk for social withdrawal, anxiety/depression, and self-destructive/identity problems, relative to recreational gamers. Overall, the different motivation subgroups were associated with different psychosocial problems. Both achievers and escapers were found to be maladaptive, but their psychosocial outcomes were different, a finding that provides further insight into the psychological mechanisms underlying these subgroups.

Endothelial-to-Mesenchymal Transition in Calcific Aortic Valve Disease.

Calcific aortic valve disease (CAVD) represents a significant threat to cardiovascular health worldwide, and the incidence of this sclerocalcific valve disease has rapidly increased along with a rise in life expectancy. Compelling evidence has suggested that CAVD is an actively and finely regulated pathophysiological process even though it has been referred to as "degenerative" for decades. A striking similarity has been noted in the etiopathogenesis between CAVD and atherosclerosis, a classical proliferative sclerotic vascular disease.1 Nevertheless, pharmaceutical trials that attempted to target inflammation and dyslipidemia have produced disappointing results in CAVD. While senescence is a well-documented risk factor, the sophisticated regulatory networks have not been adequately explored underlying the aberrant calcification and osteogenesis in CAVD. Valvular endothelial cells (VECs), a type of resident effector cells in aortic leaflets, are crucial in maintaining valvular integrity and homeostasis, and dysfunctional VECs are a major contributor to disease initiation and progression. Accumulating evidence suggests that VECs undergo a phenotypic and functional transition to mesenchymal or fibroblast-like cells in CAVD, a process known as the endothelial-to-mesenchymal transition (EndMT) process. The relevance of this transition in CAVD has recently drawn great interest due to its importance in both valve genesis at an embryonic stage and CAVD development at an adult stage. Hence EndMT might be a valuable diagnostic and therapeutic target for disease prevention and treatment. This mini-review summarized the relevant literature that delineates the EndMT process and the underlying regulatory networks involved in CAVD.

Transcatheter aortic valve implantation in the patients with chronic liver disease: A mini-review and meta-analysis.

BACKGROUND: Chronic liver disease is traditionally conceived as a risk factor for cardiovascular surgery. Transcatheter aortic valve implantation (TAVI) has recently burgeoned to precede surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis at intermediate to high surgical risk. The evidence regarding TAVI in the patients with chronic liver disease is currently scarce. METHODS: This article aims to assess the application of TAVI technique in the patients with chronic liver disease. RESULTS: TAVI in the patients with chronic liver disease produced acceptable postoperative results. The post-TAVI outcomes were comparable between the patients with or without chronic liver disease, except for a lower rate of pacemaker implantation in the patients with chronic liver disease (OR, 0.49[0.27-0.87], P = .02). In the patients with chronic liver disease, compared to SAVR, TAVI led to a decrease in the in-hospital mortality (OR, 0.43[0.22-0.86], P = .02) and need for transfusion (OR, 0.39[0.25-0.62], P < .0001). The rest outcomes were similar between the 2 groups. CONCLUSIONS: This systematic review and meta-analysis supported that TAVI is a reliable therapeutic option for treating severe aortic stenosis in the patients with chronic liver disease. Future large-scale randomized controlled trials investigating the mid-term and long-term prognosis are needed to further verify these results.

Rice GERMIN-LIKE PROTEIN 2-1 Functions in Seed Dormancy under the Control of Abscisic Acid and Gibberellic Acid Signaling Pathways.

Seed dormancy is a natural phenomenon in plants. It ensures that seeds complete the grain-filling stage before germination and prevents germination in unsuitable ecological conditions. In this study, we determined the previously unknown function of the rice (Oryza sativa) gene GERMIN-LIKE PROTEIN 2-1 (OsGLP2-1) in seed dormancy. Using artificial microRNA and CRISPR/CAS9 approaches, suppression of OsGLP2-1 expression in rice resulted in the release of dormancy in immature seeds. Conversely, overexpression of OsGLP2-1 driven by the OsGLP2-1 native promoter led to greater seed dormancy. Seed scutellum-specific expression of OsGLP2-1 was increased by exogenous abscisic acid, but decreased with gibberellic acid treatment. We provide evidence that OsGLP2-1 is antagonistically controlled at the transcriptional level by ABA INSENSITIVE5 and GAMYB transcription factors. We conclude that OsGLP2-1 acts as a buffer, maintaining appropriate equilibrium for the regulation of primary dormancy during seed development in rice.