The SMXL8-AGL9 module mediates crosstalk between strigolactone and gibberellin to regulate strigolactone-induced anthocyanin biosynthesis in apple.

Although the strigolactone (SL) signaling pathway and SL-mediated anthocyanin biosynthesis have been reported, the molecular association between SL signaling and anthocyanin biosynthesis remains unclear. In this study, we identified the SL signal transduction pathway associated with anthocyanin biosynthesis and the crosstalk between gibberellin (GA) and SL signaling in apple (Malus × domestica). ELONGATED HYPOCOTYL5 (HY5) acts as a key node integrating SL signaling and anthocyanin biosynthesis, and the SL response factor AGAMOUS-LIKE MADS-BOX9 (AGL9) promotes anthocyanin biosynthesis by activating HY5 transcription. The SL signaling repressor SUPPRESSOR OF MAX2 1-LIKE8 (SMXL8) interacts with AGL9 to form a complex that inhibits anthocyanin biosynthesis by downregulating HY5 expression. Moreover, the E3 ubiquitin ligase PROTEOLYSIS1 (PRT1) mediates the ubiquitination-mediated degradation of SMXL8, which is a key part of the SL signal transduction pathway associated with anthocyanin biosynthesis. In addition, the GA signaling repressor REPRESSOR-of-ga1-3-LIKE2a (RGL2a) mediates the crosstalk between GA and SL by disrupting the SMXL8-AGL9 interaction that represses HY5 transcription. Taken together, our study reveals the regulatory mechanism of SL-mediated anthocyanin biosynthesis and uncovers the role of SL-GA crosstalk in regulating anthocyanin biosynthesis in apple.

The MdNAC72-MdABI5 module acts as an interface integrating jasmonic acid and gibberellin signals and undergoes ubiquitination-dependent degradation regulated by MdSINA2 in apple.

Jasmonic acid (JA) and gibberellin (GA) coordinately regulate plant developmental programs and environmental cue responses. However, the fine regulatory network of the cross-interaction between JA and GA remains largely elusive. In this study, we demonstrate that MdNAC72 together with MdABI5 positively regulates anthocyanin biosynthesis through an exquisite MdNAC72-MdABI5-MdbHLH3 transcriptional cascade in apple. MdNAC72 interacts with MdABI5 to promote the transcriptional activation of MdABI5 on its target gene MdbHLH3 and directly activates the transcription of MdABI5. The MdNAC72-MdABI5 module regulates the integration of JA and GA signals in anthocyanin biosynthesis by combining with JA repressor MdJAZ2 and GA repressor MdRGL2a. MdJAZ2 disrupts the MdNAC72-MdABI5 interaction and attenuates the transcriptional activation of MdABI5 by MdNAC72. MdRGL2a sequesters MdJAZ2 from the MdJAZ2-MdNAC72 protein complex, leading to the release of MdNAC72. The E3 ubiquitin ligase MdSINA2 is responsive to JA and GA signals and promotes ubiquitination-dependent degradation of MdNAC72. The MdNAC72-MdABI5 interface fine-regulates the integration of JA and GA signals at the transcriptional and posttranslational levels by combining MdJAZ2, MdRGL2a, and MdSINA2. In summary, our findings elucidate the fine regulatory network connecting JA and GA signals with MdNAC72-MdABI5 as the core in apple.

Tailoring Charge Separation in ZnIn2S4@CdS Hollow Nanocages for Simultaneous Alcohol Oxidation and CO2 Reduction under Visible Light.

Artificial photosynthesis provides a sustainable strategy for producing usable fuels and fine chemicals and attracts broad research interest. However, conventional approaches suffer from low reactivity or low selectivity. Herein, we demonstrate that photocatalytic reduction of CO2 coupled with selective oxidation of aromatic alcohol into corresponding syngas and aromatic aldehydes can be processed efficiently and fantastically over the designed S-scheme ZnIn2S4@CdS core-shell hollow nanocage under visible light. In the ZnIn2S4@CdS heterostructure, the photoexcited electrons and holes with weak redox capacities are eliminated, while the photoexcited electrons and holes with powder redox capacities are separated spatially and preserved on the desired active sites. Therefore, even if there are no cocatalysts and no vacancies, ZnIn2S4@CdS exhibits high reactivity. For instance, the CO production of ZnIn2S4@CdS is about 3.2 and 3.4 times higher than that of pure CdS and ZnIn2S4, respectively. More importantly, ZnIn2S4@CdS exhibits general applicability and high photocatalytic stability. Trapping agent experiments, 13CO2 isotopic tracing, in situ characterizations, and theoretical calculations reveal the photocatalytic mechanism. This study provides a new strategy to design efficient and selective photocatalysts for dual-function redox reactions by tailoring the active sites and regulating vector separation of photoexcited charge carriers.

Apple SINA11-JAZ2 module is involved in jasmonate signaling response.

The E3 ubiquitin ligase MdSINA11 targets the jasmonate ZIM domain protein MdJAZ2 for ubiquitination and degradation through the 26S proteasome pathway, thereby initiating jasmonate signaling and jasmonic acid-triggered anthocyanin biosynthesis in apple.

MdbHLH162 connects the gibberellin and jasmonic acid signals to regulate anthocyanin biosynthesis in apple.

Anthocyanins are secondary metabolites induced by environmental stimuli and developmental signals. The positive regulators of anthocyanin biosynthesis have been reported, whereas the anthocyanin repressors have been neglected. Although the signal transduction pathways of gibberellin (GA) and jasmonic acid (JA) and their regulation of anthocyanin biosynthesis have been investigated, the cross-talk between GA and JA and the antagonistic mechanism of regulating anthocyanin biosynthesis remain to be investigated. In this study, we identified the anthocyanin repressor MdbHLH162 in apple and revealed its molecular mechanism of regulating anthocyanin biosynthesis by integrating the GA and JA signals. MdbHLH162 exerted passive repression by interacting with MdbHLH3 and MdbHLH33, which are two recognized positive regulators of anthocyanin biosynthesis. MdbHLH162 negatively regulated anthocyanin biosynthesis by disrupting the formation of the anthocyanin-activated MdMYB1-MdbHLH3/33 complexes and weakening transcriptional activation of the anthocyanin biosynthetic genes MdDFR and MdUF3GT by MdbHLH3 and MdbHLH33. The GA repressor MdRGL2a antagonized MdbHLH162-mediated inhibition of anthocyanins by sequestering MdbHLH162 from the MdbHLH162-MdbHLH3/33 complex. The JA repressors MdJAZ1 and MdJAZ2 interfered with the antagonistic regulation of MdbHLH162 by MdRGL2a by titrating the formation of the MdRGL2a-MdbHLH162 complex. Our findings reveal that MdbHLH162 integrates the GA and JA signals to negatively regulate anthocyanin biosynthesis. This study provides new information for discovering more anthocyanin biosynthesis repressors and explores the cross-talk between hormone signals.

Subsequent pregnancy in women who have undergone bilateral uterine artery ligation during cesarean section: A case series.

Bilateral uterine artery ligation (BUAL) serves as an effective surgical devascularization procedure in obstetric emergencies. However, concerns regarding the impact of uterine devascularization have evoked dispute. Here, the fetal growth index and obstetrical outcomes during the subsequent pregnancy of women who had undergone BUAL during cesarean section are reported. The case series of women who underwent BUAL during cesarean section and had another delivery later at the Xiamen Women and Children's Hospital between 2011 and 2020 is described. Pregnancies that did not continue beyond 20 weeks of gestation were excluded. Cases were identified from neonatal and obstetric databases and the clinical data of all cases were extracted. A total of 12 cases were identified retrospectively. Fetal biometric parameters of subsequent pregnancies in all cases including biparietal diameter, head circumference, abdominal circumference, and femur length are presented graphically across the different gestational ages and were all within the range of the 3rd-97th percentile. No maternal or neonatal morbidity was observed. BUAL did not appear to compromise a woman's subsequent obstetric outcomes. As a safe and simple surgical technique, it is safe to recommend BUAL in clinical practice.

Pattern recognition of microcirculation with super-resolution ultrasound imaging provides markers for early tumor response to anti-angiogenic therapy.

Rationale: Cancer treatment outcome is traditionally evaluated by tumor volume change in clinics, while tumor microvascular heterogeneity reflecting tumor response has not been fully explored due to technical limitations. Methods: We introduce a new paradigm in super-resolution ultrasound imaging, termed pattern recognition of microcirculation (PARM), which identifies both hemodynamic and morphological patterns of tumor microcirculation hidden in spatio-temporal space trajectories of microbubbles. Results: PARM demonstrates the ability to distinguish different local blood flow velocities separated by a distance of 24 µm. Compared with traditional vascular parameters, PARM-derived heterogeneity parameters prove to be more sensitive to microvascular changes following anti-angiogenic therapy. Particularly, PARM-identified "sentinel" microvasculature, exhibiting evident structural changes as early as 24 hours after treatment initiation, correlates significantly with subsequent tumor volume changes (|r| > 0.9, P < 0.05). This provides prognostic insight into tumor response much earlier than clinical criteria. Conclusions: The ability of PARM to noninvasively quantify tumor vascular heterogeneity at the microvascular level may shed new light on early-stage assessment of cancer therapy.

Apple E3 ligase MdPUB23 mediates ubiquitin-dependent degradation of MdABI5 to delay ABA-triggered leaf senescence.

ABSCISIC ACID-INSENSITIVE5 (ABI5) is a core regulatory factor that mediates the ABA signaling response and leaf senescence. However, the molecular mechanism underlying the synergistic regulation of leaf senescence by ABI5 with interacting partners and the homeostasis of ABI5 in the ABA signaling response remain to be further investigated. In this study, we found that the accelerated effect of MdABI5 on leaf senescence is partly dependent on MdbHLH93, an activator of leaf senescence in apple. MdABI5 directly interacted with MdbHLH93 and improved the transcriptional activation of the senescence-associated gene MdSAG18 by MdbHLH93. MdPUB23, a U-box E3 ubiquitin ligase, physically interacted with MdABI5 and delayed ABA-triggered leaf senescence. Genetic and biochemical analyses suggest that MdPUB23 inhibited MdABI5-promoted leaf premature senescence by targeting MdABI5 for ubiquitin-dependent degradation. In conclusion, our results verify that MdABI5 accelerates leaf senescence through the MdABI5-MdbHLH93-MdSAG18 regulatory module, and MdPUB23 is responsible for the dynamic regulation of ABA-triggered leaf senescence by modulating the homeostasis of MdABI5.

Thermal Activation of High-Alumina Coal Gangue Auxiliary Cementitious Admixture: Thermal Transformation, Calcining Product Formation and Mechanical Properties.

In this paper, a new preparation technology is developed to make high-alumina coal gangue (HACG) auxiliary cementitious admixture by calcining HACG-Ca(OH)2 (CH) mixture. HACG powders mixed with 20 wt.% CH were calcined within a temperature range of 600-900 °C, and the thermal transformation and mineral phase formation were analyzed. The hydration reaction between activated HACG-CH mixture and cement was also investigated. The results showed that HACG experienced a conventional transformation from kaolinite to metakaolin at 600 °C and finally to mullite at 900 °C, whereas CH underwent an unexpected transformation process from CH to CaO, then to CaCO3, and finally to CaO again. These substances' states were associated with the dehydroxylation of CH, the chemical reaction between CaO and CO2 generating from the combustion of carbon in HACG, and the decomposition of CaCO3, respectively. It is the formation of a large amount of CaO above 800 °C that favors the formation of hydratable products containing Al2O3 in the calcining process and C-A-H gel in the hydration process. The mechanical properties of HACG-cement mortar specimens were measured, from which the optimal calcination temperature of 850 °C was determined. As compared with pure cement mortar specimens, the maximum 28-d flexural and compressive strengths of HACG-cement mortar specimens increased by 5.4% and 38.2%, respectively.

Programmable ultrasound imaging guided theranostic nanodroplet destruction for precision therapy of breast cancer.

Ultrasound-stimulated contrast agents have gained significant attention in the field of tumor treatment as drug delivery systems. However, their limited drug-loading efficiency and the issue of bulky, imprecise release have resulted in inadequate drug concentrations at targeted tissues. Herein, we developed a highly efficient approach for doxorubicin (DOX) precise release at tumor site and real-time feedback via an integrated strategy of "programmable ultrasonic imaging guided accurate nanodroplet destruction for drug release" (PND). We synthesized DOX-loaded nanodroplets (DOX-NDs) with improved loading efficiency (15 %) and smaller size (mean particle size: 358 nm). These DOX-NDs exhibited lower ultrasound activation thresholds (2.46 MPa). By utilizing a single diagnostic transducer for both ultrasound stimulation and imaging guidance, we successfully vaporized the DOX-NDs and released the drug at the tumor site in 4 T1 tumor-bearing mice. Remarkably, the PND group achieved similar tumor remission effects with less than half the dose of DOX required in conventional treatment. Furthermore, the ultrasound-mediated vaporization of DOX-NDs induced tumor cell apoptosis with minimal damage to surrounding normal tissues. In summary, our PND strategy offers a precise and programmable approach for drug delivery and therapy, combining ultrasound imaging guidance. This approach shows great potential in enhancing tumor treatment efficacy while minimizing harm to healthy tissues.

H2O2-triggered CO release based on porphyrinic covalent organic polymers for photodynamic/gas synergistic therapy.

A novel H2O2-responsive carbon monoxide nanogenerator was designed by effectively encapsulating a manganese carbonyl prodrug into porphyrinic covalent organic polymers for realizing the combined CO gas and photodynamic therapy under near infrared light irradiation.

Ozone rectal insufflation mitigates chronic rapid eye movement sleep deprivation-induced cognitive impairment through inflammation alleviation and gut microbiota regulation in mice.

A range of sleep disorders has the potential to adversely affect cognitive function. This study was undertaken with the objective of investigating the effects of ozone rectal insufflation (O3-RI) on cognitive dysfunction induced by chronic REM sleep deprivation, as well as elucidating possible underlying mechanisms. O3-RI ameliorated cognitive dysfunction in chronic REM sleep deprived mice, improved the neuronal damage in the hippocampus region and decreased neuronal loss. Administration of O3-RI may protect against chronic REM sleep deprivation induced cognitive dysfunction by reversing the abnormal expression of Occludin and leucine-rich repeat and pyrin domain-containing protein 3 inflammasome as well as interleukin-1ß in the hippocampus and colon tissues. Moreover, the microbiota diversity and composition of sleep deprivation mice were significantly affected by O3-RI intervention, as evidenced by the reversal of the Firmicutes/Bacteroidetes abundance ratio and the relative abundance of the Bacteroides genus. In particular, the relative abundance of the Bacteroides genus demonstrated a pronounced correlation with cognitive impairment and inflammation. Our findings suggested that O3-RI can improve cognitive dysfunction in sleep deprivation mice, and its mechanisms may be related to regulating gut microbiota and alleviating inflammation and damage in the hippocampus and colon.

Biolimus-coated versus paclitaxel-coated balloons for coronary in-stent restenosis (BIO ASCEND ISR): a randomised, non-inferiority trial.

BACKGROUND: The treatment of in-stent restenosis (ISR) after drug-eluting stent (DES) implantation remains challenging in current clinical practice. AIMS: The study was conducted to investigate a novel biolimus-coated balloon (BCB) for the treatment of coronary DES-ISR compared with the best-investigated paclitaxel-coated balloon (PCB). METHODS: This was a prospective, multicentre, randomised, non-inferiority trial comparing a novel BCB with a clinically proven PCB for coronary DES-ISR. The primary endpoint was in-segment late lumen loss (LLL) at 9 months assessed by an independent core laboratory. Baseline and follow-up optical coherence tomography were performed in a prespecified subgroup of patients. RESULTS: A total of 280 patients at 17 centres were randomised to treatment with a BCB (n=140) versus a PCB (n=140). At 9 months, LLL in the BCB group was 0.23±0.37 mm compared to 0.25±0.35 mm in the PCB group; the mean difference between the groups was -0.02 (95% confidence interval [CI]: -0.12 to 0.07) mm; p-value for non-inferiority<0.0001. Similar clinical outcomes were also observed for both groups at 12 months. In the optical coherence tomography substudy, the neointimal area at 9 months was 2.32±1.04 mm2 in the BCB group compared to 2.37±0.93 mm2 in the PCB group; the mean difference between the groups was -0.09 (95% CI: -0.94 to 0.76) mm2; p=non-significant. CONCLUSIONS: This head-to-head comparison of a novel BCB shows similar angiographic outcomes in the treatment of coronary DES-ISR compared with a clinically proven PCB. (ClinicalTrials.gov: NCT04733443).

Effectiveness and Safety of a Novel Intravascular Lithotripsy System for Severe Coronary Calcification: The CALCI-CRACK Trial.

BACKGROUND: Intravascular lithotripsy is effective and safe for managing coronary calcification; however, available devices are limited, and complex lesions have been excluded in previous studies. This study aimed to investigate the effectiveness and safety of a novel intravascular lithotripsy system for severe calcification in a population with complex lesions. METHODS: CALCI-CRACK (treatment of severe calcified coronary lesions with a novel intracoronary shock wave lithotripsy system) (ChiCTR2100052058) was a prospective, single-arm, multicentre study. The primary end point was the procedural success rate. Major safety end points included major adverse cardiovascular events (MACE) and target lesion failure (TLF) at 30 days and 6 months, and severe angiographic complications. Calcification morphology was assessed in the optical coherence tomography (OCT) subgroup. RESULTS: In total, 242 patients from 15 high-volume Chinese centres were enrolled, including 26.45% of patients with true bifurcation lesions, 3.31% with severely tortuous vessels, and 2.48% with chronic total occlusion, respectively. The procedural success rate was 95.04% (95% confidence interval 91.50%-97.41%), exceeding the prespecified performance goal of 83.4% (P < 0.001). The 30-day and 6-month MACE rates were 4.13% and 4.55%, respectively. TLF rates at those time points were 1.24% and 1.65%, respectively. Severe angiographic complications occurred in 0.42% of patients. In the OCT subgroup (n = 93), 93.55% of calcified lesions were fractured, and minimal lumen area increased from 1.55 ± 0.55 mm2 to 4.91 ± 1.22 mm2 after stent implantation, with acute gain rate of 245 ± 102%. CONCLUSIONS: The novel intravascular lithotripsy system is effective and safe for managing severely calcified coronary lesions in a cohort that included true bifurcation lesions, severely tortuous vessels, and chronic total occlusion. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR), number ChiCTR2100052058.

Dexmedetomidine prevents spatial learning and memory impairment induced by chronic REM sleep deprivation in rats.

The study was attempted to investigate the effect on and mechanisms of action of dexmedetomidine with regard to learning and memory impairment in rats with chronic rapid eye movement (REM) sleep deprivation. A total of 50 male Sprague Dawley rats were randomly divided into five groups. Modified multiple platform method was conducted to cause the sleep deprivation of rats. Dexmedetomidine and midazolam were administered by intraperitoneal injection. Learning and memory ability was assessed through Morris water maze. Morphological changes of rat hippocampal neurons and synaptic were detected by transmission electron microscope and Golgi staining. The gene expression in hippocampus of each group was detected by RNA-seq and verified by RT-PCR and western blot. REM Sleep-deprived rats exhibited spatial learning and memory deficits. Furthermore, there was decreased density of synaptic spinous in the hippocampal CA1 region of the sleep deprivation group compared with the control. Additionally, transmission electron microscopy showed that the synaptic gaps of hippocampal neurons in REM sleep deprivation group were loose and fuzzy. Interestingly, dexmedetomidine treatment normalized these events to control levels following REM sleep deprivation. Molecular biological methods showed that Alox15 expression increased significantly after REM sleep deprivation as compared to control, while dexmedetomidine administration reversed the expression of Alox15. Dexmedetomidine alleviated the spatial learning and memory dysfunction induced with chronic REM sleep deprivation in rats. This protective effect may be related to the down-regulation of Alox15 expression and thereby the enhancement of synaptic structural plasticity in the hippocampal CA1 area of rats. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-023-00450-8.

Explore artificial neural networks for solving complex hydrocarbon chemistry in turbulent reactive flows.

Global warming caused by the use of fossil fuels is a common concern of the world today. It is of practical importance to conduct in-depth fundamental research and optimal design for modern engine combustors through high-fidelity computational fluid dynamics (CFD), so as to achieve energy conservation and emission reduction. However, complex hydrocarbon chemistry, an indispensable component for predictive modeling, is computationally demanding. Its application in simulation-based design optimization, although desirable, is quite limited. To address this challenge, we propose a methodology for representing complex chemistry with artificial neural networks (ANNs), which are trained with a comprehensive sample dataset generated by the Latin hypercube sampling (LHS) method. With a given chemical kinetic mechanism, the thermochemical sample data is able to cover the whole accessible pressure/temperature/species space in various turbulent flames. The ANN-based model consists of two different layers: the self-organizing map (SOM) and the back-propagation neural network (BPNN). The methodology is demonstrated to represent a 30-species methane chemical mechanism. The obtained ANN model is applied to simulate both a non-premixed turbulent flame (DLR_A) and a partially premixed turbulent flame (Flame D) to validate its applicability for different flames. Results show that the ANN-based chemical kinetics can reduce the computational cost by about two orders of magnitude without loss of accuracy. The proposed methodology can successfully construct an ANN-based chemical mechanism with significant efficiency gain and a broad scope of applicability, and thus holds a great potential for complex hydrocarbon fuels.