Self-supervised Pre-training via Multi-view Graph Information Bottleneck for Molecular Property Prediction.

Molecular representation learning has remarkably accelerated the development of drug analysis and discovery. It implements machine learning methods to encode molecule embeddings for diverse downstream drug-related tasks. Due to the scarcity of labeled molecular data, self-supervised molecular pre-training is promising as it can handle large-scale unlabeled molecular data to prompt representation learning. Although many universal graph pre-training methods have been successfully introduced into molecular learning, there still exist some limitations. Many graph augmentation methods, such as atom deletion and bond perturbation, tend to destroy the intrinsic properties and connections of molecules. In addition, identifying subgraphs that are important to specific chemical properties is also challenging for molecular learning. To address these limitations, we propose the self-supervised Molecular Graph Information Bottleneck (MGIB) model for molecular pre-training. MGIB observes molecular graphs from the atom view and the motif view, deploys a learnable graph compression process to extract the core subgraphs, and extends the graph information bottleneck into the self-supervised molecular pre-training framework. Model analysis validates the contribution of the self-supervised graph information bottleneck and illustrates the interpretability of MGIB through the extracted subgraphs. Extensive experiments involving molecular property prediction, including 7 binary classification tasks and 6 regression tasks demonstrate the effectiveness and superiority of our proposed MGIB.

Acute effects of eccentric overload training with different loading doses in male sprinters.

Objective: The primary objective of this study was to investigate the immediate effects of two doses (Dose1 and Dose2,D1 and D2) of inertial Flywheel Eccentric Overload (FEOL), Eccentric Hook (EH), and High-intensity Half Squat (HHS) on muscle explosiveness in male sprinters. Methods: Twenty-one sub-elite male sprinters were randomly assigned to three groups: the FEOL group (n=7), the EH group (n=7), and the HSS group (n=7),Measurements of athletes' explosive jumps (CMJ, SJ, SLJ) heights, relative peak power indices, and 30-m sprint times were collected before and 6 min after the intervention. Results: At D1 loading dose, CMJ, SJ jump height, and relative peak power increased significantly (p < 0.05) after HHS training intervention, while there was no significant change in FEOL and EH training (p > 0.05). At D2 loading dose, CMJ, SJ jump height, and relative peak power increased significantly (p < 0.01) after FEOL and EH training intervention, but at D2HHS intervention, these indexes tended to decrease (p < 0.05). None of the three training protocols significantly improved SLJ performance (p > 0.05). CMJ vertical jump height and relative peak power were significantly higher after D2FEOL and D2EH interventions than after D1HHS (P < 0.05). Conclusion: D1HHS, D2FEOL and D2EH3 intervention methods can all improve the performance of sub-elite athletes in the 30-m test, CMJ test and SJ test. in the CMJ test, FEOL training demonstrated a higher acute augmentation effect compared to EH training.

Biodegradable Ferroelectric Molecular Plastic Crystal HOCH2(CF2)7CH2OH Structurally Inspired by Polyvinylidene Fluoride.

Ferroelectric materials, traditionally comprising inorganic ceramics and polymers, are commonly used in medical implantable devices. However, their nondegradable nature often necessitates secondary surgeries for removal. In contrast, ferroelectric molecular crystals have the advantages of easy solution processing, lightweight, and good biocompatibility, which are promising candidates for transient (short-term) implantable devices. Despite these benefits, the discovered biodegradable ferroelectric materials remain limited due to the absence of efficient design strategies. Here, inspired by the polar structure of polyvinylidene fluoride (PVDF), a ferroelectric molecular crystal 1H,1H,9H,9H-perfluoro-1,9-nonanediol (PFND), which undergoes a cubic-to-monoclinic ferroelectric plastic phase transition at 339 K, is discovered. This transition is facilitated by a 2D hydrogen bond network formed through O-H···O interactions among the oriented PFND molecules, which is crucial for the manifestation of ferroelectric properties. In this sense, by reducing the number of -CF2- groups from ≈5 000 in PVDF to seven in PFND, it is demonstrated that this ferroelectric compound only needs simple solution processing while maintaining excellent biosafety, biocompatibility, and biodegradability. This work illuminates the path toward the development of new biodegradable ferroelectric molecular crystals, offering promising avenues for biomedical applications.

Salvage surgery and conversion surgery for patients with non-small cell lung cancer: A narrative review.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths. With the development of screening, patient selection and treatment strategies, patients' survival outcomes and living quality significantly improved. However, some patients still have local recurrence or residual tumors after receiving definitive therapies. Salvage surgery has been regarded as an effective option for recurrent or residual NSCLC, but its effectiveness remains undetermined. Furthermore, conversion surgery is a special type of salvage surgery for tumors converted from "initially unresectable" to "potentially resectable" status due to a favorable response to systemic treatments. Although conversion surgery is a promising curative procedure for advanced NSCLC, its concept and clinical value remain unfamiliar to clinicians. In this narrative review, we provided an overview of the safety and efficacy of salvage surgery, especially salvage surgery after sublobar resection in early-stage NSCLC. More importantly, we highlighted the concept and value of conversion surgery after systemic treatment in advanced NSCLC to gain some insights into its role in the treatment of lung cancer.

Multicolor tunable persistent luminescence mechanism in well-designed inorganic composites.

Herein, by ball milling CsPb(Br/I)3 quantum dot glass powder with Sr2MgSi2O7:Eu2+, Dy3+ phosphor, multicolor tunable long persistent luminescence (LPL) in inorganic composites with more than 700 min attenuation time can be obtained via a radiation photon reabsorption process. Attractively, the wide color gamut of LPL spectra overlaps the National Television System Committee space 74%. Notably, the luminescence intensity remains stable when the inorganic composites are composed with UV light for 100 h. Finally, practical anticounterfeiting application is successfully realized based on the prepared LPL inorganic composites. This work provides a new, to the best of our knowledge, perspective to achieve polychromatic adjustment of LPL.

DEK219 and HSF17 Collaboratively Regulate the Kernel Length in Maize.

The kernel length is a crucial determinant of maize (Zea mays L.) yield; however, only a limited number of genes regulating kernel length have been validated, thus leaving our understanding of the mechanisms governing kernel length incomplete. We previously identified a maize kernel mutant, defective kernel219 (dek219), which encodes the DICER-LIKE1 protein that is essential for miRNA biogenesis. The present study revealed that dek219 consistently exhibits a stable phenotype characterized by a reduced kernel length. Further analysis indicated that dek219 may reduce the kernel length by inhibiting the expression of genes involved in regulating kernel length. By employing miRNA-target gene prediction, expression analysis, and correlation analysis, we successfully identified nine transcription factors that potentially participate in the regulation of kernel length under the control of DEK219. Among them, the upregulation fold change of HEAT SHOCK TRANSCRIPTION FACTOR17 (HSF17) expression was the highest, and the difference was most significant. The results of transient expression analysis and electrophoretic mobility shift assay (EMSA) indicated that HSF17 can inhibit the expression of DEFECTIVE ENDOSPERM18 (DE18), a gene involved in regulating kernel length. Furthermore, the hsf17 mutant exhibited a significant increase in kernel length, suggesting that HSF17 functions as a negative regulator of kernel length. The results of this study provide crucial evidence for further elucidating the molecular regulatory mechanism underlying maize kernel length and also offer valuable genetic resources for breeding high-yielding maize varieties.

PCSK9 Inhibitor Added to High-Intensity Statin Therapy to Prevent Cardiovascular Events in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Randomized, Double- Blind, Placebo-Controlled, Multicenter SHAWN Study.

BACKGROUND: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. METHODS: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at one-year follow-up between two groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. CONCLUSION: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.

Recent design strategies for boosting chemodynamic therapy of bacterial infections.

The emergence of drug-resistant bacteria poses a significant threat to people's lives and health as bacterial infections continue to persist. Currently, antibiotic therapy remains the primary approach for tackling bacterial infections. However, the escalating rates of drug resistance coupled with the lag in the development of novel drugs have led to diminishing effectiveness of conventional treatments. Therefore, the development of nonantibiotic-dependent therapeutic strategies has become imperative to impede the rise of bacterial resistance. The emergence of chemodynamic therapy (CDT) has opened up a new possibility due to the CDT can convert H2O2 into •OH via Fenton/Fenton-like reaction for drug-resistant bacterial treatment. However, the efficacy of CDT is limited by a variety of practical factors. To overcome this limitation, the sterilization efficiency of CDT can be enhanced by introducing the therapeutics with inherent antimicrobial capability. In addition, researchers have explored CDT-based combined therapies to augment its antimicrobial effects and mitigate its potential toxic side effects toward normal tissues. This review examines the research progress of CDT in the antimicrobial field, explores various strategies to enhance CDT efficacy and presents the synergistic effects of CDT in combination with other modalities. And last, the current challenges faced by CDT and the future research directions are discussed.

Method to quickly estimate T1 value by suppressing spin exchange relaxation and magnetic field gradient relaxation in atomic sensors.

The accuracy of atomic sensor is determined by the transverse nuclear spin relaxation time (T2). As the longitudinal nuclear spin relaxation time (T1) is the upper limit of T2, it becomes an important metric for evaluating the merits of alkali vapor cells. However, the conventional method for measuring T1 of pulse delay takes dozens of minutes, which will increase the effect of random errors during the testing process. In order to solve this problem, a method to quickly estimate the value of T1 is proposed by suppressing the influence of spin exchange relaxation and magnetic field gradient relaxation terms on T2. Experimental results indicate that the accuracy is maintained at above 95%, and the testing time is reduced to less than 5%.

Multiparametric MRI-based radiomics analysis for prediction of lymph node metastasis and survival outcome in gastric cancer: A dual-center study.

RATIONALE AND OBJECTIVES: Gastric cancer (GC) is highly heterogeneous, and accurate preoperative assessment of lymph node status remains challenging. We aimed to develop a multiparametric MRI-based model for predicting lymph node metastasis (LNM) in GC and to explore its prognostic implications. MATERIALS AND METHODS: In this dual-center retrospective study, 479 GC patients undergoing preoperative multiparametric MRI before radical gastrectomy were enrolled. 1595 imaging features were extracted from T2-weighted imaging, apparent diffusion coefficient maps, and contrast-enhanced T1-weighted imaging (cT1WI), respectively. Feature selection steps, including the Boruta and Simulated Annealing algorithms, were conducted to identify key features. Different radiomics models (RMs) based on the single- and multiple-sequence were constructed. The performance of various RMs in predicting LNM was assessed in terms of discrimination, calibration, and clinical usefulness. Additionally, Kaplan-Meier survival curves were employed to estimate differences in disease-free survival (DFS) and overall survival (OS). RESULTS: The multi-sequence radiomics model (MRM) achieved area under the curves (AUCs) of 0.774 [95 % confidence interval (CI), 0.703-0.845], 0.721 (95 % CI, 0.593-0.850), and 0.720 (95 % CI, 0.639-0.801) in the training and two validation cohorts, respectively, outperforming the single-sequence RMs. Notably, the RM derived from cT1WI demonstrated superior performance compared to the other two single-sequence models. Furthermore, the proposed MRM exhibited a significant association with DFS and OS in GC patients (both P < 0.05). CONCLUSION: The multiparametric MRI-based radiomics model, derived from primary lesions, demonstrated moderate performance in predicting LNM and survival outcomes in patients with GC, which could provide valuable insights for personalized treatment strategies.

Pathological Mechanism and Treatment of Calcified Aortic Stenosis.

Calcified aortic stenosis (AS) is one of the most common valvular heart diseases worldwide, characterized by progressive fibrocalcific remodeling and thickening of the leaflets, which ultimately leads to obstruction of blood flow. Its pathobiology is an active and complicated process, involving endothelial cell dysfunction, lipoprotein deposition and oxidation, chronic inflammation, phenotypic transformation of valve interstitial cells, neovascularization, and intravalvular hemorrhage. To date, no targeted drug has been proven to slow down or prevent disease progression. Aortic valve replacement is still the optimal treatment of AS. This article reviews the etiology, diagnosis, and management of calcified aortic stenosis and proposes novel potential therapeutic targets.

Correction: A tactile and airflow motion sensor based on flexible double-layer magnetic cilia.

[This corrects the article DOI: 10.1038/s41378-022-00478-9.].

Nanopore-regulated in situ polymerization for synthesis of homogeneous heparan sulfate with low dispersity.

The biological activities of heparan sulfate (HS) are intimately related to their molecular weights, degree and pattern of sulfation and homogeneity. The existing methods for synthesizing homogeneous sugar chains of low dispersity involve multiple steps and require stepwise isolation and purification processes. Here, we designed a mesoporous metal-organic capsule for the encapsulation of glycosyltransferase and obtained a microreactor capable of enzymatically catalyzing polymerization reactions to prepare homogeneous heparosan of low dispersity, the precursor of HS and heparin. Since the sugar chain extension occurs in the pores of the microreactor, low molecular weight heparosan can be synthesized through space-restricted catalysis. Moreover, the glycosylation co-product, uridine diphosphate (UDP), can be chelated with the exposed metal sites of the metal-organic capsule, which inhibits trans-cleavage to reduce the molecular weight dispersity. This microreactor offers the advantages of efficiency, reusability, and obviates the need for stepwise isolation and purification processes. Using the synthesized heparosan, we further successfully prepared homogeneous 6-O-sulfated HS of low dispersity with a molecular weight of approximately 6 kDa and a polydispersity index (PDI) of 1.032. Notably, the HS generated exhibited minimal anticoagulant activity, and its binding affinity to fibroblast growth factor 1 was comparable to that of low molecular weight heparins.

Microbial Diversity Associated with the Cabernet Sauvignon Carposphere (Fruit Surface) from Eight Vineyards in Henan Province, China.

The microbial diversity on the carposphere (berry) surface of the grape cultivar Cabernet Sauvignon grown in eight different locations/vineyards of Henan Province was determined by high-throughput sequencing of the bacterial 16S rRNA gene and fungal 18S rRNA gene. The structure of bacterial and fungal communities varied according to the sampling sites, but with some common phyla. Proteobacteria and Ascomycota were dominant/common phyla for bacteria and fungi, respectively. A total of 27 and 20 bacterial and fungal families, respectively, and 39 and 20 bacterial and fungal genera, respectively, with statistically significant differences, were found among different sampling sites. The difference for metabolic pathways of bacteria among the sampling sites existed. In addition, various abundances of enzymes from different sites might indicate that different function patterns exist in microbiota from different sites. The results revealed that locations of grape vineyards might play a significant role in shaping the microbiome, as well as the fact that vineyards can be distinguished based on the abundance of several key bacterial and fungal taxa. Overall, these findings extend our understanding of the similarities and differences in microbial community and their metabolic function on Cabernet Sauvignon grape surfaces from different geographic locations.

Fractional Fourier-transform off-axis digital holographic imaging.

A fractional Fourier-transform digital holographic imaging method with resolution enhancement features is presented. In an optical configuration, an extended fractional Fourier-transform optical setup is set in the object arm of an off-axis digital holographic recording system to record a fractional Fourier-transform hologram via the optical interference of the fractional Fourier-transform wavefront of an object wave with a reference wave. For reconstruction imaging, the reconstruction approach for fractional Fourier-transform holograms is given. In the experiment, the fractional Fourier-transform digital holograms are recorded under the different recording parameters, and their amplitude images are effectively reconstructed. The imaging results demonstrate that the reconstruction-imaging resolution of fractional-order Fourier-transform holograms is obviously enhanced compared to that of conventional image-plane holograms. The presented fractional Fourier-transform digital holographic imaging with resolution enhancement and optical configuration flexibility provides, to our knowledge, a novel way for off-axis digital holographic imaging.

Effects of prolonged application of peracetic acid-based disinfectant on recirculating aquaculture systems stocked with Atlantic salmon parr.

The use of recirculating aquaculture systems (RAS) for Atlantic salmon (Salmo salar) production has become increasingly common. RAS water disinfection plays a crucial role on its biosecurity. Peracetic acid (PAA) is a promising disinfectant due to its powerful oxidative properties, broad antimicrobial spectrum, and rapid degradation into no harmful compounds. This study focused on assessing the consequences of prolonged application of a PAA-based disinfectant in a RAS stocked with salmon parr. The experiment included three treatment groups in triplicate: 0 mg/L PAA (control), 0.1 mg/L PAA, and 1 mg/L PAA, using nine-replicated RAS with a total of 360 fish (14.8 ± 2.3 g; N = 40/RAS). The study spanned 28 days, with samples collected on days 0, 14, and 28. The analyzed parameters were water quality, and fish parameters, including external welfare indicators, gill histology, total antioxidant capacity (TAC), reactive oxygen species/reactive nitrogen species (ROC/RNC), oxidative stress biomarkers related to DNA and protein, cellular DNA damage, and global gene expression. While water quality remained relatively stable, there was an increase in bacterial populations in the groups exposed to PAA, particularly 1 mg/L PAA. Fish weight did not differ between the control and PAA-exposed groups. TAC, ROC/RNC, and oxidative stress biomarkers exhibited similar trends. The study identified >400 differentially expressed genes (DEGs) in the skin, gill, and olfactory organ, with many of these DEGs associated with immune responses. Comparing the transcriptomic profiles of the three tissue organs revealed that the olfactory organ was the most reactive to PAA treatment. This study shows that calculated PAA concentrations of 0.1 mg/L and 1 mg/L in the pump-sump, contributed to an increase of bacteria whereas no detectable differences in health and welfare of salmon parr were found. These findings are promising for the implementation of PAA-based disinfectants in RAS stoked with Atlantic salmon parr.

Frequency-modulated alternating current-driven bioelectrodes for enhanced mineralization of Alizarin Yellow R.

The alternating current (AC)-driven bioelectrochemical process, in-situ coupling cathodic reduction and anodic oxidation in a single electrode, offers a promising way for the mineralization of refractory aromatic pollutants (RAPs). Frequency modulation is vital for aligning reduction and oxidation phases in AC-driven bioelectrodes, potentially enhancing their capability to mineralize RAPs. Herein, a frequency-modulated AC-driven bioelectrode was developed to enhance RAP mineralization, exemplified by the degradation of Alizarin Yellow R (AYR). Optimal performance was achieved at a frequency of 1.67 mHz, resulting in the highest efficiency for AYR decolorization and subsequent mineralization of intermediates. Performance declined at both higher (3.33 and 8.30 mHz) and lower (0.83 mHz) frequencies. The bioelectrode exhibited superior electron utilization, bidirectional electron transfer, and redox bifunctionality, effectively aligning reduction and oxidation processes to enhance AYR mineralization. The 1.67 mHz frequency facilitated the assembly of a collaborative microbiome dedicated to AYR bio-mineralization, characterized by an increased abundance of functional consortia proficient in azo dye reduction (e.g., Stenotrophomonas and Shinella), aromatic intermediates oxidation (e.g., Sphingopyxis and Sphingomonas), and electron transfer (e.g., Geobacter and Pseudomonas). This study reveals the role of frequency modulation in AC-driven bioelectrodes for enhanced RAP mineralization, offering a novel and sustainable approach for treating RAP-bearing wastewater.

Angiographic Findings and Post-Percutaneous Coronary Intervention Fractional Flow Reserve.

Importance: The associations between angiographic findings and post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) and their clinical relevance according to residual functional disease burden have not been thoroughly investigated. Objectives: To evaluate the association of angiographic and physiologic parameters according to residual functional disease burden after drug-eluting stent implantation. Design, Setting, and Participants: This cohort study population was from the International Post-PCI FFR registry, which incorporated 4 registries from Korea, China, and Japan. Patients who underwent angiographically successful second-generation drug-eluting stent implantation and post-PCI FFR measurement were included in the analysis. The patients were divided into 3 groups according to the residual disease burden (post-PCI FFR ≤0.80 [residual ischemia], 0.81-0.86 [suboptimal], and >0.86 [optimal]). The data were collected from August 23, 2018, to June 11, 2019, and the current analysis was performed from January 11, 2022, to October 7, 2023. Exposures: Angiographic parameters and post-PCI FFR. Main Outcomes and Measures: The primary outcome was target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction, and target vessel revascularization (TVR) at 2 years. Results: In this cohort of 2147 patients, the mean (SD) age was 64.3 (10.0) years, and 1644 patients (76.6%) were men. Based on the post-PCI physiologic status, 269 patients (12.5%) had residual ischemia, 551 (25.7%) had suboptimal results, and 1327 (61.8%) had optimal results. Angiographic parameters had poor correlations with post-PCI FFR (r < 0.20). Post-PCI FFR was isolated from all angiographic parameters in the unsupervised hierarchical cluster analysis. Post-PCI FFR was associated with the occurrence of TVF (adjusted hazard ratio [AHR] per post-PCI FFR 0.01 increase, 0.94 [95% CI, 0.92-0.97]; P < .001), but angiographic parameters were not. The residual ischemia group had a significantly higher rate of TVF than the suboptimal group (AHR, 1.75 [95% CI, 1.08-2.83]; P = .02) and the optimal group (AHR, 2.94 [95% CI, 1.82-4.73]; P < .001). The TVR in the residual ischemia group was predominantly associated with TVR in the nonstented segment (14 [53.8%]), unlike the other 2 groups (3 [10.0%] in the suboptimal group and 13 [30.2%] in the optimal group). Conclusions and Relevance: In this cohort study of the International Post-PCI FFR registry, a low degree of associations were observed between angiographic and physiologic parameters after PCI. Post-PCI FFR, unlike angiographic parameters, was associated with clinical events and the distribution of clinical events. The current study supports the use of post-PCI FFR as a procedural quality metric and further prospective study is warranted.

Alcohol exposure during pregnancy induces cardiac mitochondrial damage in offspring mice.

BACKGROUND: Prenatal alcohol exposure (PAE) has been linked to congenital heart disease and fetal alcohol syndrome. The heart primarily relies on mitochondria to generate energy, so impaired mitochondrial function due to alcohol exposure can significantly affect cardiac development and function. Our study aimed to investigate the impact of PAE on myocardial and mitochondrial functions in offspring mice. METHODS: We administered 30% alcohol (3 g/kg) to pregnant C57BL/6 mice during the second trimester. We assessed cardiac function by transthoracic echocardiography, observed myocardial structure and fibrosis through staining tests and electron transmission microscopy, and detected cardiomyocyte apoptosis with dUTP nick end labeling assay and real-time quantitative PCR. Additionally, we measured the reactive oxygen species content, ATP level, and mitochondrial DNA copy number in myocardial mitochondria. Mitochondrial damage was evaluated by assessing the level of mitochondrial membrane potential and the opening degree of mitochondrial permeability transition pores. RESULTS: Our findings revealed that PAE caused cardiac systolic dysfunction, ventricular enlargement, thinned ventricular wall, cardiac fibrosis in the myocardium, scattered loss of cardiomyocytes, and disordered arrangement of myocardial myotomes in the offspring. Furthermore, we observed a significant increase in mitochondrial reactive oxygen species content, a decrease in mitochondrial membrane potential, ATP level, and mitochondrial DNA copy number, and sustained opening of mitochondrial permeability transition pores in the heart tissues of the offspring. CONCLUSIONS: These results indicated that PAE had adverse effects on the cardiac structure and function of the newborn mice and could trigger oxidative stress in their myocardia and contribute to mitochondrial dysfunction.

The lncRNA1-miR6288b-3p-PpTCP4-PpD2 module regulates peach branch number by affecting brassinosteroid biosynthesis.

Branch number is one of the most important agronomic traits of fruit trees such as peach. Little is known about how LncRNA and/or miRNA modules regulate branching through transcription factors. Here, we used molecular and genetic tools to clarify the molecular mechanisms underlying brassinosteroid (BR) altering plant branching. We found that the number of sylleptic branch and BR content in pillar peach ('Zhaoshouhong') was lower than those of standard type ('Okubo'), and exogenous BR application could significantly promote branching. PpTCP4 expressed great differentially comparing 'Zhaoshouhong' with 'Okubo'. PpTCP4 could directly bind to DWARF2 (PpD2) and inhibited its expression. PpD2 was the only one differentially expressed key gene in the path of BR biosynthesis. At the same time, PpTCP4 was identified as a target of miR6288b-3p. LncRNA1 could act as the endogenous target mimic of miR6288b-3p and repress expression of miR6288b-3p. Three deletions and five SNP sites of lncRNA1 promoter were found in 'Zhaoshouhong', which was an important cause of different mRNA level of PpTCP4 and BR content. Moreover, overexpressed PpTCP4 significantly inhibited branching. A novel mechanism in which the lncRNA1-miR6288b-3p-PpTCP4-PpD2 module regulates peach branching number was proposed.