A rotational/roto-translational constraint method for condensed matter.

Molecular rotations influence numerous condensed matter phenomena but are often difficult to isolate in molecular dynamics (MD) simulations. This work presents a rotational/roto-translational constraint algorithm designed for condensed matter simulations. The method is based on the velocity Verlet scheme, ensuring a direct constraint on velocity and simplifying implementation within material simulation software packages. We implemented the algorithm in a customized version of a CP2K package and validated its effectiveness through MD simulations of molecule and crystal. The results demonstrate successful selective constraint of rotational and roto-translational motions, enabling stable long-term simulations. This capability opens avenues for studying rotation-related phenomena (e.g., paddle-wheel mechanism in solid-state electrolytes) and constrained sampling.

Mitophagy Promotes Hair Regeneration by Activating Glutathione Metabolism.

Mitophagy maintains tissue homeostasis by self-eliminating defective mitochondria through autophagy. How mitophagy regulates stem cell activity during hair regeneration remains unclear. Here, we found that mitophagy promotes the proliferation of hair germ (HG) cells by regulating glutathione (GSH) metabolism. First, single-cell RNA sequencing, mitochondrial probe, transmission electron microscopy, and immunofluorescence staining showed stronger mitochondrial activity and increased mitophagy-related gene especially Prohibitin 2 (Phb2) expression at early-anagen HG compared to the telogen HG. Mitochondrial inner membrane receptor protein PHB2 binds to LC3 to initiate mitophagy. Second, molecular docking and functional studies revealed that PHB2-LC3 activates mitophagy to eliminate the damaged mitochondria in HG. RNA-seq, single-cell metabolism, immunofluorescence staining, and functional validation discovered that LC3 promotes GSH metabolism to supply energy for promoting HG proliferation. Third, transcriptomics analysis and immunofluorescence staining indicated that mitophagy was down-regulated in the aged compared to young-mouse HG. Activating mitophagy and GSH pathways through small-molecule administration can reactivate HG cell proliferation followed by hair regeneration in aged hair follicles. Our findings open up a new avenue for exploring autophagy that promotes hair regeneration and emphasizes the role of the self-elimination effect of mitophagy in controlling the proliferation of HG cells by regulating GSH metabolism.

Less risk of patellofemoral degeneration without significant clinical and survivorship difference for distal tibial tuberosity high tibial osteotomy compared to biplanar high tibial osteotomy over a mid-term follow-up.

PURPOSE: This study aims to compare the mid-term radiographic, clinical results and survivorship between distal tibial tuberosity high tibial osteotomy (DTT-HTO) and conventional biplanar medial open-wedge high tibial osteotomy (cOW-HTO). METHODS: The weight-bearing line ratio (WBL%) and medial proximal tibial angle (MPTA) were evaluated using a standing anteroposterior view of lower extremity. The posterior tibial slope (PTS), Caton-Deschamps index (CDI), tilting angle (TT) and lateral shift ratio (LSR) were evaluated using the lateral views and Merchant views. The Knee Society (KS) knee and function score, Lysholm score, and Anterior Knee Pain Scale (Kujala score) were were used to evaluate the functional outcomes. All parameters were evaluated preoperatively and at the final follow-up. The postoperative complications and survivorship for both groups were also evaluated during the follow-up period. RESULTS: The WBL% and MPTA exhibited no significant differences between the two groups preoperatively and at the final follow-up. The postoperative CDI and TT in the cOW group decreased significantly compared with the DTT group (p = .037 and .041, respectively). The PF grade showed a significant increase after DTT-HTO and cOW-HTO (p = .036 and <0.001, respectively). Furthermore, the postoperative PF grade of cOW group was significantly higher than that of DTT group (p = .039). The KS knee and function score, Lysholm score, and Kujala score for both groups improved similarly at the final follow-up. The survivorship free of revision was 92.7 % in the DTT group and 94.2% in the OW group. CONCLUSIONS: Despite observing a lower risk of PF joint progression in DTT-HTO compared to cOW-HTO, the clinical outcomes and survivorship after DTT-HTO and cOWHTO were comparable over a mid-term follow-up.

One-year outcomes of a novel venous stent for symptomatic iliofemoral venous obstruction: prospective cohort study.

BACKGROUND: A stent with characteristics of a hybrid design may have advantages in improving the patency of symptomatic iliofemoral vein obstruction. This study assessed the safety and effectiveness of the V-Mixtent Venous Stent in treating symptomatic iliofemoral outflow obstruction. METHODS: Eligible patients had a Clinical-Etiologic-Anatomic-Physiologic (CEAP) C classification of ≥ 3 or a Venous Clinical Severity Score (VCSS) pain score of ≥ 2. The primary safety endpoint was the rate of major adverse events within 30 days. The primary effectiveness endpoint was the 12-month primary patency rate. Secondary endpoints included changes in VCSS from baseline to 6 and 12 months, alterations in CEAP C classification, Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-14) scores at 12 months, and stent durability measures. RESULTS: Between December 2020 and November 2021, 171 patients were enrolled across 15 institutions. A total of 185 endovenous stents were placed, with 91.81% of subjects receiving one stent and 8.19% receiving 2 stents. Within 30 days, only two major adverse events occurred (1.17%; 95% confidence interval [CI], 0.14-4.16%), below the literature-defined performance goal of 11% (P < .001). The 12-month primary patency rate (91.36%; 95% CI, 85.93-95.19%; P < .001) exceeded the literature-defined performance goal. VCSS changes from baseline demonstrated clinical improvement at 6 months (- 4.30 ± 3.66) and 12 months (- 4.98 ± 3.67) (P < .001). Significant reduction in symptoms, as measured by CEAP C classification and CIVIQ-14, was observed from pre-procedure to 12 months (P < .001). CONCLUSIONS: The 12-month outcomes confirm the safety and effectiveness of the V-Mixtent Venous Stent in managing symptomatic iliofemoral venous outflow obstruction, including clinical symptom improvement compared to before treatment.

Multi-modal triggered-release sonodynamic/chemo/phototherapy synergistic nanocarriers for the treatment of colon cancer.

Most colon cancer patients are diagnosed at an advanced stage, with a grim prognosis. In clinical, various combination therapies have been employed to enhance the efficacy of colon cancer treatment. The essence of combined treatment is the judicious selection and combination of various treatment units. Phototherapy (PT), sonodynamic therapy (SDT), and chemotherapy are treatment modalities that rely on the active molecules to treat tumors, and have been demonstrated to synergistically enhance tumor treatment efficacy. However, the differences in the metabolism of active molecules and hypoxic microenvironment of tumors have limited the synergistic effects of the aforementioned methods. To address this significant issue, in this study, we utilized polydopamine (PDA) as the encapsulated material to form a rigid shell that contains the therapeutic molecules IR-780 and methotrexate (MTX) on the surface of perfluorohexane (PFH) microdroplets through self-assembling method to develop an SDT/chemotherapy/PT combined nanoparticles (SCP NPs). Transmission electron microscopy (TEM) revealed that the nanoparticles exhibited a hollow shell structure, with an average size of approximately 100 nm. SCP NPs have excellent stability and biocompatibility in both in vitro and in vivo. The absorption and emission spectrum of the loaded IR-780 did not exhibit any significant shift, and the photothermal temperature rose to 92°C. Their ultrasonic cavitation effect was good and their cell inhibitory effect of MTX was maintained. SCP NPs can achieve multi-modal triggered release through ultrasound, laser irradiation, and pH, ensuring a simultaneous accumulation of therapeutic molecules in the tumor area and effectively alleviating tumor hypoxia. Additionally, both the near-infrared fluorescence (NIF) signal and the ultrasonic cavitation signal of the nanoparticles can be utilized for tracking and monitoring treatment efficacy. Most notably, SCP NPs exhibited outstanding synergistic treatment effects at low intervention levels, resulting in a 67% cure rate of tumors. These results provide an experimental basis for developing the new clinical treatments for colon cancer.

Revealing and reconstructing the 3D Li-ion transportation network for superionic poly(ethylene) oxide conductor.

Understanding the Li-ions conduction network and transport dynamics in polymer electrolyte is crucial for developing reliable all-solid-state batteries. In this work, advanced nano- X-ray computed tomography combined with Raman spectroscopy and solid state nuclear magnetic resonance are used to multi-scale qualitatively and quantitatively reveal ion conduction network of poly(ethylene) oxide (PEO)-based electrolyte (from atomic, nano to macroscopic level). With the clear mapping of the microstructural heterogeneities of the polymer segments, aluminium-oxo molecular clusters (AlOC) are used to reconstruct a high-efficient conducting network with high available Li-ions (76.7%) and continuous amorphous domains via the strong supramolecular interactions. Such superionic PEO conductor (PEO-LiTFSI-AlOC) exhibites a molten-like Li-ion conduction behaviour among the whole temperature range and delivers an ionic conductivity of 1.87 × 10-4 S cm-1 at 35 °Ï¹. This further endows Li electrochemical plating/stripping stability under 50 µA cm-2 and 50 µAh cm-2 over 2000 h. The as-built Li|PEO-LiTFSI-AlOC|LiFePO4 full batteries show a high rate performance and a capacity retention more than 90% over 200 cycling at 250 µA cm-2, even enabling a high-loading LiFePO4 cathode of 16.8 mg cm-2 with a specific capacity of 150 mAh g-1 at 50 °Ï¹.

Hydroxyl radical mediated extracellular degradation of tetracycline under aerobic and anaerobic conditions stimulated by bio-FeS nanoparticles.

The extracellular degradation of antibiotics facilitated by bio-nanoparticles is significant in the field of waste valorization. Among different bio-nanoparticles, bio-FeS nanoparticles stand out for their convenient and cost-effective synthesis. Nevertheless, there is a lack of understanding regarding the extracellular degradation of pollutants driven by bio-FeS nanoparticles. Hence, this study aimed to investigate the role of bio-FeS nanoparticles in the extracellular degradation of tetracycline under aerobic and anaerobic conditions. The findings demonstrated that bio-FeS nanoparticles generated hydroxyl radical (·OH), which significantly contributes to the degradation of tetracycline in both aerobic and anaerobic environments. The production of ·OH in anaerobic conditions was primarily attributed to the limited formation of FeS2 during the biosynthesis of nanoparticles, which was very different from aerobic conditions. The bio-FeS nanoparticles facilitated extracellular electron transport by promoting electron shuttles and Fe(II)/Fe(III) cycling, resulting in the continuous production of ·OH. The degradation pathways showed differences under aerobic and anaerobic conditions, with intermediates exhibiting higher toxicity and greater cellular damage under aerobic conditions. However, in anaerobic conditions, bio-FeS nanoparticles enabled the successful integration of intracellular and extracellular degradation of tetracycline. This research proposed a new avenue for biocatalysis and environmental remediation.

Immunometabolic interplay in Edwardsiella tarda-infected crucian carp (Carassius auratus) and in vitro identification of the antimicrobial activity of apolipoprotein D (ApoD) by utilization of multiomics analyses.

Edwardsiella tarda is an intracellular pathogenic bacteria that can imperil the health of farmed fish. However, the interactive networks of immune regulation and metabolic response in E. tarda-infected fish are still unclear. In this investigation, we aimed to explore immunometabolic interplay in crucian carp after E. tarda infection by utilizing multiomics analyses. Crucian carp (Carassius auratus) receiving E. tarda infection showed increased levels of tissue damage and oxidative injury in liver. Multiomics analyses suggested that carbon and amino acid metabolism may be considered as crucial metabolic pathways in liver of crucian carp following E. tarda infection, while spaglumic acid, isocitric acid and tetrahydrocortisone were the crucial liver biomarkers. After that, a potential antimicrobial peptide (AMP) sequence called apolipoprotein D (ApoD) was identified from omics study. Then, tissue-specific analysis indicated that liver CaApoD showed the highest expression among isolated tissues. After Aeromonas hydrophila stimulated, CaApoD expressions increased sharply in immune-related tissues. Moreover, CaApoD fusion protein could mediate the in vitro binding to A. hydrophila and E. tarda, attenuate bacterial growth as well as diminish bacterial biofilm forming activity. These findings may have a comprehensive implication for understanding immunometabolic response in crucian carp upon infection.

Acoustofluidic Virus Isolation via Bessel Beam Excitation Separation Technology.

The isolation of viruses from complex biological samples is essential for creating sensitive bioassays that assess the efficacy and safety of viral therapeutics and vaccines, which have played a critical role during the COVID-19 pandemic. However, existing methods of viral isolation are time-consuming and labor-intensive due to the multiple processing steps required, resulting in low yields. Here, we introduce the rapid, efficient, and high-resolution acoustofluidic isolation of viruses from complex biological samples via Bessel beam excitation separation technology (BEST). BEST isolates viruses by utilizing the nondiffractive and self-healing properties of 2D, in-plane acoustic Bessel beams to continuously separate cell-free viruses from biofluids, with high throughput and high viral RNA yield. By tuning the acoustic parameters, the cutoff size of isolated viruses can be easily adjusted to perform dynamic, size-selective virus isolation while simultaneously trapping larger particles and separating smaller particles and contaminants from the sample, achieving high-precision isolation of the target virus. BEST was used to isolate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from human saliva samples and Moloney Murine Leukemia Virus from cell culture media, demonstrating its potential use in both practical diagnostic applications and fundamental virology research. With high separation resolution, high yield, and high purity, BEST is a powerful tool for rapidly and efficiently isolating viruses. It has the potential to play an important role in the development of next-generation viral diagnostics, therapeutics, and vaccines.

Artificial intelligence in individualized retinal disease management.

Owing to the rapid development of modern computer technologies, artificial intelligence (AI) has emerged as an essential instrument for intelligent analysis across a range of fields. AI has been proven to be highly effective in ophthalmology, where it is frequently used for identifying, diagnosing, and typing retinal diseases. An increasing number of researchers have begun to comprehensively map patients' retinal diseases using AI, which has made individualized clinical prediction and treatment possible. These include prognostic improvement, risk prediction, progression assessment, and interventional therapies for retinal diseases. Researchers have used a range of input data methods to increase the accuracy and dependability of the results, including the use of tabular, textual, or image-based input data. They also combined the analyses of multiple types of input data. To give ophthalmologists access to precise, individualized, and high-quality treatment strategies that will further optimize treatment outcomes, this review summarizes the latest findings in AI research related to the prediction and guidance of clinical diagnosis and treatment of retinal diseases.

Multi-Tissue Integrated Tissue-Engineered Trachea Regeneration Based on 3D Printed Bioelastomer Scaffolds.

Functional segmental trachea reconstruction is a critical concern in thoracic surgery, and tissue-engineered trachea (TET) holds promise as a potential solution. However, current TET falls short in fully restoring physiological function due to the lack of the intricate multi-tissue structure found in natural trachea. In this research, a multi-tissue integrated tissue-engineered trachea (MI-TET) is successfully developed by orderly assembling various cells (chondrocytes, fibroblasts and epithelial cells) on 3D-printed PGS bioelastomer scaffolds. The MI-TET closely resembles the complex structures of natural trachea and achieves the integrated regeneration of four essential tracheal components: C-shaped cartilage ring, O-shaped vascularized fiber ring, axial fiber bundle, and airway epithelium. Overall, the MI-TET demonstrates highly similar multi-tissue structures and physiological functions to natural trachea, showing promise for future clinical advancements in functional TETs.

The predictive value of intraoperative bulbocavernosus re?ex monitoring for postoperative voiding function in patients with conus medullaris and cauda equina tumors: a retrospective single center study.

BACKGROUND CONTEXT: Surgical resection is the preferred treatment in most conus medullaris and cauda equina tumor (CMCET) cases. However, total resection is usually challenging to obtain and has a strong possibility of causing various complications if forcibly attempted. Intraoperative neurophysiological monitoring (IONM) has become a necessary adjunctive tool for CMCET resection. PURPOSE: The current study aimed to evaluate the application value of bulbocavernosus reflex (BCR) monitoring in CMCET surgery. STUDY DESIGN: A retrospective clinical study. PATIENT SAMPLE: The medical records of patients who underwent CMCET resection by the same neurosurgical team at our hospital from September 2020 to June 2022 were retrospectively reviewed. IONM was conducted in all surgeries. According to inclusion criteria and exclusion criteria, ultimately, 105 patients were enrolled in the study. OUTCOME MEASURES: The voiding function was assessed before surgery, one month after, and six months after surgery using the Neurogenic Bladder Symptom Score (NBSS). If the NBSS obtained one month after surgery exceeds 9 points than that before surgery, it can be considered that the patient suffered new-onset postoperative voiding dysfunctions (PVDs). Moreover, if the NBSS could restored (less than 9 points higher than before the surgery) at six months after surgery, it was defined as a short-term PVD. Otherwise, it was defined as a long-term PVD. METHODS: The amplitude reduction ratios (ARRs) of bilateral BCR waveforms were calculated and compared between patients with PVDs and those without. The receiver operating characteristic curve analysis was subsequently applied to determine the cut-off value of the maximal and minimal ARRs for predicting PVDs. RESULTS: The maximal and minimal ARRs were significantly correlated with short-term and long-term PVDs (p<0.001 for all comparisons, Mann-Whitney U test). The threshold values of maximal ARR for predicting short-term and long-term PVD were 68.80% (AUC=0.996, p<0.001) and 72.10% (AUC=0.996, p<0.001), respectively. While those of minimal ARR were 50.20% (AUC=0.976, p<0.001) and 53.70% AUC=0.999, p<0.001). CONCLUSIONS: The amplitude reduction of intraoperative bilateral BCR waveforms showed high predictive value for PVDs.

Discovery of novel ULK1 inhibitors through machine learning-guided virtual screening and biological evaluation.

Aim: Build a virtual screening model for ULK1 inhibitors based on artificial intelligence. Materials & methods: Build machine learning and deep learning classification models and combine molecular docking and biological evaluation to screen ULK1 inhibitors from 13 million compounds. And molecular dynamics was used to explore the binding mechanism of active compounds. Results & conclusion: Possibly due to less available training data, machine learning models significantly outperform deep learning models. Among them, the Naive Bayes model has the best performance. Through virtual screening, we obtained three inhibitors with IC50 of µM level and they all bind well to ULK1. This study provides an efficient virtual screening model and three promising compounds for the study of ULK1 inhibitors.

[Box: see text].

Bubble-Guidance Breaking Gas Shield for Highly Efficient Overall Water Splitting.

Overall water splitting is a promising technology for sustainable hydrogen production, but the primary challenge is removing bubbles from the electrode surface quickly to increase hydrogen production. Inspired by the directional fluid transport properties of natural biological surfaces like Nepenthes peristome and Morpho butterfly's wings, here a strategy is demonstrated to achieve highly efficient overall water splitting by a bubble-guidance electrode, that is, an anisotropic groove-micro/nanostructured porous electrode (GMPE). Gradient groove micro/nanostructures on the GMPE serve as high-speed bubble transmission channels and exhibit superior bubble-guidance capabilities. The synergistic effect of the asymmetric Laplace pressure generated between microscale porous structure and groove patterns and the buoyancy along the groove patterns pushes the produced bubbles directionally to spread, transport, and detach from the electrode surface in time. Moreover, the low adhesive nanosheet arrays are beneficial to reduce bubble size and increase bubble release frequency, which cooperatively improve mass transfer with the microscale structure. Notably, GMPE outperforms planar-micro/nanostructured porous electrode (PMPE) in hydrogen/oxygen evolution reactions, with GMPE||GMPE showing better water splitting performance than commercially available RuO2||20 wt.% Pt/C. This work improves electrodes for better mass transfer and kinetics in electrochemical reactions at solid-liquid-gas interfaces, offering insight for designing and preparing gas-involved photoelectrochemical electrodes.

Thiadiazol ligand-based laccase-like nanozymes with a high Cu+ ratio for efficient removal of tetracyclines through polymerization.

A promising water treatment technology involves inducing the polymerization of organic pollutants to form corresponding polymers, enabling rapid, efficient, and low CO2 emission removal of these pollutants. However, there is currently limited research on utilizing polymerization treatment technology for removing tetracyclines from water. In this study, we synthesized a laccase-mimic nanozyme (Cu-ATZ) with a high Cu+ ratio using 2-amino-1,3,4-thiadiazole as a ligand inspired by natural laccase. The Cu-ATZ exhibited enhanced resistance to more severe application conditions and improved stability compared to natural laccase, thereby demonstrating a broader range of potential applications. The excellent catalytic properties of Cu-ATZ enabled the nanozyme to be used in the polymerization process to remove tetracyclines from water. In order to simulate actual antibiotic pollution of water bodies, tetracyclines were added to the water from sewage treatment plants. Following Cu-ATZ treatment of the water sample, the chemical oxygen demand (COD) content was found to have decreased by over 80 %. In conclusion, this study presented a novel approach for tetracycline elimination from water.

Telehealth-Supported Exercise or Physical Activity Programs for Knee Osteoarthritis: Systematic Review and Meta-Analysis.

BACKGROUND: The integration of telehealth-supported programs in chronic disease management has become increasingly common. However, its effectiveness for individuals with knee osteoarthritis (KOA) remains unclear. OBJECTIVE: This study aimed to assess the effectiveness of telehealth-supported exercise or physical activity programs for individuals with KOA. METHODS: A comprehensive literature search encompassing Embase, MEDLINE, CENTRAL, Web of Science, PubMed, Scopus, PEDro, GreyNet, and medRxiv from inception to September 2023 was conducted to identify randomized controlled trials comparing telehealth-supported exercise or physical activity programs to a control condition for KOA. Data were extracted and qualitatively synthesized across eligible studies, and a meta-analysis was performed to evaluate the effects. The study was reported according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020. RESULTS: In total, 23 studies met eligibility criteria, with 20 included in the meta-analysis. Results showed that telehealth-supported exercise or physical activity programs reduced pain (g=-0.39; 95% CI -0.67 to -0.11; P<.001), improved physical activity (g=0.13; 95% CI 0.03-0.23; P=.01), and enhanced physical function (g=-0.51; 95% CI -0.98 to -0.05; P=.03). Moreover, significant improvements in quality of life (g=0.25; 95% CI 0.14-0.36; P<.001), self-efficacy for pain (g=0.72; 95% CI 0.53-0.91; P<.001), and global improvement (odds ratio 2.69, 95% CI 1.41-5.15; P<.001) were observed. However, self-efficacy for physical function (g=0.14; 95% CI -0.26 to 0.53; P=.50) showed insignificant improvements. Subgroup analyses based on the World Health Organization classification of digital health (pain: χ22=6.5; P=.04 and physical function: χ22=6.4; P=.04), the type of teletechnology in the intervention group (pain: χ24=4.8; P=.31 and function: χ24=13.0; P=.01), and active or inactive controls (pain: χ21=5.3; P=.02 and physical function: χ21=3.4; P=.07) showed significant subgroup differences. CONCLUSIONS: Telehealth-supported exercise or physical activity programs might reduce knee pain and improve physical activity, physical function, quality of life, self-efficacy, and global improvement in individuals with KOA. Future research should consider longer implementation durations and assess the feasibility of incorporating wearables and standardized components into large-scale interventions to evaluate the effects. TRIAL REGISTRATION: PROSPERO CRD42022359658; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=359658.

Protein kinase MeSnRK2.3 positively regulates starch biosynthesis by interacting with the transcription factor MebHLH68 in cassava.

Starch biosynthesis involves numerous enzymes and is a crucial metabolic activity in plant storage organs. Sucrose non-fermenting related protein kinase 2 (SnRK2) is an abscisic acid (ABA)-dependent kinase and a significant regulatory enzyme in the ABA signaling pathway. However, whether SnRK2 kinases regulate starch biosynthesis is unclear. In this study, we identified that MeSnRK2.3, an ABA-dependent kinase, was highly expressed in the storage roots of cassava and was induced by ABA. Overexpression of MeSnRK2.3 in cassava significantly increased the starch content in the storage roots and promoted plant growth. MeSnRK2.3 was further found to interact with the cassava basic helix-loop-helix 68 (MebHLH68) transcription factor in vivo and in vitro. MebHLH68 directly bound to the promoters of sucrose synthase 1 (MeSUS1), granule-bound starch synthase I a (MeGBSSIa), and starch-branching enzyme 2.4 (MeSBE2.4), thereby upregulating their transcriptional activities. Additionally, MebHLH68 negatively regulated the transcriptional activity of sucrose phosphate synthase B (MeSPSB). Moreover, phosphorylated MebHLH68 by MeSnRK2.3 up-regulated the transcription activity of MeSBE2.4. These findings demonstrated that the MeSnRK2.3-MebHLH68 module connects the ABA signaling pathway and starch biosynthesis in cassava, thereby providing direct evidence of ABA-mediated participation in the sucrose metabolism and starch biosynthesis pathway.

Polyphenol-Reinforced Glycocalyx-Like Hydrogel Coating Induced Myocardial Regeneration and Immunomodulation.

Although minimally invasive interventional occluders can effectively seal heart defect tissue, they still have some limitations, including poor endothelial healing, intense inflammatory response, and thrombosis formation. Herein, a polyphenol-reinforced medicine/peptide glycocalyx-like coating was prepared on cardiac occluders. A coating consisting of carboxylated chitosan, epigallocatechin-3-gallate (EGCG), tanshinone IIA sulfonic sodium (TSS), and hyaluronic acid grafted with 3-aminophenylboronic acid was prepared. Subsequently, the mercaptopropionic acid-GGGGG-Arg-Glu-Asp-Val peptide was grafted by the thiol-ene "click" reaction. The coating showed good hydrophilicity and free radical-scavenging ability and could release EGCG-TSS. The results of biological experiments suggested that the coating could reduce thrombosis by promoting endothelialization, and promote myocardial repair by regulating the inflammatory response. The functions of regulating cardiomyocyte apoptosis and metabolism were confirmed, and the inflammatory regulatory functions of the coating were mainly dependent on the NF-kappa B and TNF signaling pathway.

Solving Expensive Optimization Problems in Dynamic Environments With Meta-Learning.

Dynamic environments pose great challenges for expensive optimization problems, as the objective functions of these problems change over time and thus require remarkable computational resources to track the optimal solutions. Although data-driven evolutionary optimization and Bayesian optimization (BO) approaches have shown promise in solving expensive optimization problems in static environments, the attempts to develop such approaches in dynamic environments remain rarely explored. In this article, we propose a simple yet effective meta-learning-based optimization framework for solving the expensive dynamic optimization problems. This framework is flexible, allowing any off-the-shelf continuously differentiable surrogate model to be used in a plug-in manner, either in data-driven evolutionary optimization or BO approaches. In particular, the framework consists of two unique components: 1) the meta-learning component, in which a gradient-based meta-learning approach is adopted to learn experience (effective model parameters) across different dynamics along the optimization process and 2) the adaptation component, where the learned experience (model parameters) is used as the initial parameters for fast adaptation in the dynamic environment based on few shot samples. By doing so, the optimization process is able to quickly initiate the search in a new environment within a strictly restricted computational budget. Experiments demonstrate the effectiveness of the proposed algorithm framework compared to several state-of-the-art algorithms on common benchmark test problems under different dynamic characteristics.

Substituted indole derivatives as UNC-51-like kinase 1 inhibitors: Design, synthesis and anti-hepatocellular carcinoma activity.

The five-year survival rate for patients with hepatocellular carcinoma (HCC) is only 20 %, highlighting the urgent need to identify new therapeutic targets and develop potential therapeutic options to improve patient prognosis. One promising approach is inhibiting autophagy as a strategy for HCC treatment. In this study, we established a virtual docking conformation of the autophagy promoter ULK1 binding XST-14 derivatives. Based on this conformation, we designed and synthesized four series of derivatives. By evaluating their affinity and anti-HCC effects, we confirmed that these compounds exert anti-HCC activity by inhibiting ULK1. The structure-activity relationship was summarized, with derivative A4 showing 10 times higher activity than XST-14 and superior efficacy to sorafenib against HCC. A4 has excellent effect on reducing tumor growth and enhancing sorafenib activity in HepG2 and HCCLM3 cells. Moreover, we verified the therapeutic effect of A4 in sorafenib-resistant HCC cells both in vivo and in vitro. These results suggest that inhibiting ULK1 to regulate autophagy may become a new treatment method for HCC and that A4 will be used as a lead drug for HCC in further research. Overall, A4 shows good drug safety and efficacy, offering hope for prolonging the survival of HCC patients.