Whole-genome sequencing of a worldwide collection of sugarcane cultivars (Saccharum spp.) reveals the genetic basis of cultivar improvement.

Sugarcane is the main source of sugar worldwide, and 80% of the sucrose production comes from sugarcane. However, the genetic differentiation and basis of agronomic traits remain obscure. Here, we sequenced the whole-genome of 219 elite worldwide sugarcane cultivar accessions. A total of approximately 6 million high-quality genome-wide single nucleotide polymorphisms (SNPs) were detected. A genome-wide association study identified a total of 2198 SNPs that were significantly associated with sucrose content, stalk number, plant height, stalk diameter, cane yield, and sugar yield. We observed homozygous tendency of favor alleles of these loci, and over 80% of cultivar accessions carried the favor alleles of the SNPs or haplotypes associated with sucrose content. Gene introgression analysis showed that the number of chromosome segments from Saccharum spontaneum decreased with the breeding time of cultivars, while those from S. officinarum increased in recent cultivars. A series of selection signatures were identified in sugarcane improvement procession, of which 104 were simultaneously associated with agronomic traits and 45 of them were mainly associated with sucrose content. We further proposed that as per sugarcane transgenic experiments, ShN/AINV3.1 plays a positive role in increasing stalk number, plant height, and stalk diameter. These findings provide comprehensive resources for understanding the genetic basis of agronomic traits and will be beneficial to germplasm innovation, screening molecular markers, and future sugarcane cultivar improvement.

C-Terminal Binding Protein: Regulator between Viral Infection and Tumorigenesis.

C-terminal binding protein (CtBP), a transcriptional co-repressor, significantly influences cellular signaling, impacting various biological processes including cell proliferation, differentiation, apoptosis, and immune responses. The CtBP family comprises two highly conserved proteins, CtBP1 and CtBP2, which have been shown to play critical roles in both tumorigenesis and the regulation of viral infections. Elevated CtBP expression is noted in various tumor tissues, promoting tumorigenesis, invasiveness, and metastasis through multiple pathways. Additionally, CtBP's role in viral infections varies, exhibiting differing or even opposing effects depending on the virus. This review synthesizes the advances in CtBP's function research in viral infections and virus-associated tumorigenesis, offering new insights into potential antiviral and anticancer strategies.

Cu-Tremella fuciformis polysaccharide-based tumor microenvironment-responsive injectable gels for cuproptosis-based synergistic osteosarcoma therapy.

Cuproptosis affects osteosarcoma locally, and the exploitation of cuproptosis-related biomaterials for osteosarcoma treatment is still in its infancy. We designed and synthesized a novel injectable gel of Cu ion-coordinated Tremella fuciformis polysaccharide (TFP-Cu) for antiosteosarcoma therapy. This material has antitumor effects, the ability to stimulate immunity and promote bone formation, and a controlled Cu2+ release profile in smart response to tumor microenvironment stimulation. TFP-Cu can selectively inhibit the proliferation of K7M2 tumor cells by arresting the cell cycle and promoting cell apoptosis and cuproptosis. TFP-Cu also promoted the M1 polarization of RAW264.7 cells and regulated the immune microenvironment. These effects increased osteogenic gene and protein expression in MC3T3-E1 cells. TFP-Cu could significantly limit tumor growth in tumor-bearing mice by inducing tumor cell apoptosis and improving the activation of anti-CD8 T cell-mediated immune responses. Therefore, TFP-Cu could be a potential candidate for treating osteosarcoma and bioactive drug carrier for further cancer-related applications.

Sonodynamic Therapy-Driven Immunotherapy: Constructing AIE Organic Sonosensitizers Using an Advanced Receptor-Regulated Strategy.

Benefit from the deeper penetration of mechanical wave, ultrasound (US)-based sonodynamic therapy (SDT) executes gratifying efficacy in treating deep-seated tumors. Nevertheless, the complicated mechanism of SDT undeniably hinders the exploration of ingenious sonosensitizers. Herein, a receptor engineering strategy of aggregation-induced emission (AIE) sonosensitizers (TPA-Tpy) with acceptor (A)-donor (D)-A' structure is proposed, which inspects the effect of increased cationizations on US sensitivity. Under US stimulation, enhanced cationization in TPA-Tpy improves intramolecular charge transfer (ICT) and accelerates charge separation, which possesses a non-negligible promotion in type I reactive oxygen species (ROS) production. Moreover, abundant ROS-mediated mitochondrial oxidative stress triggers satisfactory immunogenic cell death (ICD), which further promotes the combination of SDT and ICD. Subsequently, subacid pH-activated nanoparticles (TPA-Tpy NPs) are constructed with charge-converting layer (2,3-dimethylmaleic anhydride-poly (allylamine hydrochloride)-polyethylene glycol (DMMA-PAH-PEG)) and TPA-Tpy, achieving the controllable release of sonosensitizers. In vivo, TPA-Tpy-mediated SDT effectively initiates the surface-exposed of calreticulin (ecto-CRT), dendritic cells (DCs) maturation, and CD8+ T cell infiltration rate through enhanced ROS production, achieving suppression and ablation of primary and metastatic tumors. This study provides new opinions in regulating acceptors with eminent US sensitization, and brings a novel ICD sono-inducer based on SDT to realize superior antitumor effect.

Elevated type I IFN signalling directly affects CD8+ T-cell distribution and autoantigen recognition of the skeletal muscles in active JDM patients.

The link between type I IFN and adaptive immunity, especially T-cell immunity, in JDM still remained largely unclear. This study aimed to understand the effect of elevated type I IFN signaling on CD8+ T cell-associated muscle damage in juvenile dermatomyositis (JDM). This study used flow cytometry (FC) and RT‒PCR were used to examine the circulating cell ratio and type I IFN response. And scRNA-seq was used to examine peripheral immunity in 6 active JDM patients, 3 stable JDM patients, 3 juvenile IMNM patients and 3 age-matched healthy children. In vivo validation experiments were conducted using a mouse model induced by STING agonists and an experimental autoimmune myositis model (EAM). In vitro experiments were conducted using isolated CD8+ T-cells from JDM patients and mice. We found that active JDM patients showed an extensive type I IFN response and a decreased CD8+ T-cell ratio in the periphery (P < 0.05), which was correlated with muscle involvement (P < 0.05). Both new active JDM patients and all active JDM patients showed decreased CD8+ TCM cell ratios compared with age and gender matched stable JDM patients (P < 0.05). Compared with new pediatirc systemic lupus erythematosus (SLE) patients, new active JDM patients displayed decreased CD8+ T-cell and CD8+ TCM cell ratios (P < 0.05). Active JDM patient skeletal muscle biopsies displayed an elevated type I IFN response, upregulated MHC-I expression and CD8+ T-cell infiltration, which was validated in EAM mice. sc-RNAseq demonstrated that type I IFN signalling is the kinetic factor of abnormal differentiation and enhances the cytotoxicity of peripheral CD8+ T cells in active JDM patients, which was confirmed by in vivo and in vitro validation experiments. In summary, the elevated type I IFN signalling affected the differentiation and function of CD8+ T cells in active JDM patients. Skeletal muscle-infiltrating CD8+ T cells might migrate from the periphery under the drive of type I IFN and increased MHC I signals. Therapies targeting autoantigen-specific CD8+ T cells may represent a potential new treatment direction.

The beneficial rhizobacterium Bacillus velezensis SQR9 regulates plant nitrogen uptake via an endogenous signaling pathway.

Nitrogen fertilizer is widely used in agriculture to boost crop yields. Plant growth-promoting rhizobacteria (PGPRs) can increase plant nitrogen use efficiency through nitrogen fixation and organic nitrogen mineralization. However, it is not known whether they can activate plant nitrogen uptake. In this study, we investigated the effects of volatile compounds (VCs) emitted by the PGPR strain Bacillus velezensis SQR9 on plant nitrogen uptake. Strain SQR9 VCs promoted nitrogen accumulation in both rice and Arabidopsis. In addition, isotope labeling experiments showed that strain SQR9 VCs promoted the absorption of nitrate and ammonium. Several key nitrogen-uptake genes were up-regulated by strain SQR9 VCs, such as AtNRT2.1 in Arabidopsis and OsNAR2.1, OsNRT2.3a, and OsAMT1 family members in rice, and the deletion of these genes compromised the promoting effect of strain SQR9 VCs on plant nitrogen absorption. Furthermore, calcium and the transcription factor NIN-LIKE PROTEIN 7 play an important role in nitrate uptake promoted by strain SQR9 VCs. Taken together, our results indicate that PGPRs can promote nitrogen uptake through regulating plant endogenous signaling and nitrogen transport pathways.

Effectiveness, safety and indications of acute normovolemic haemodilution in total knee arthroplasty.

Total knee arthroplasty (TKA) is the most cost-effective, and potent method for the treatment of end-stage knee osteoarthritis. Acute normovolemic haemodilution (ANH) can effectively replace the need for allogeneic transfusions due to the high amount of bleeding during TKA. However, more studies are needed to prove the efficacy and safety of ANH and to clarify its indications in the field of knee replacement. Medical records from June 1, 2019 to June 1, 2021 were searched and grouped according to inclusion and exclusion criteria. PART I: 58 patients with ANH during TKA were selected as the ANH group (n = 58), and 58 patients with allogeneic transfusion were chosen as the control group (n = 58). PART II: Patients with anaemia were divided into the ANH group (n = 18) and the control group (n = 12). PART I: The postoperative inflammatory index and serum albumin in the ANH group were significantly lower than those in the control group. No significant difference was observed in the theoretical loss of red blood cells, postoperative renal function, liver function, cardiac function and biochemical ion index between the two groups. The effective rate of ANH in the normal haemoglobin group was significantly lower than that in the anaemia group. PART II: In patients with anaemia, the theoretical loss of red blood cells in patients with ANH was less than that in the control group. The postoperative inflammation, renal function, liver function and cardiac function in the ANH group were better than those in the control group, and no significant difference was noted in biochemical ions and nutritional status indicators. This paper shows that ANH not only can replace allogeneic transfusion in TKA, especially in patients with anaemia, but also has lower inflammatory indicators than allogeneic transfusion. From a security perspective, the body's tolerance to ANH is within the body's compensation range.

Signal communication during microbial modulation of root system architecture.

Every living organism on Earth depends on its interactions with other organisms. In the rhizosphere, plants and microorganisms constantly exchange signals and influence each other's behavior. Recent studies have shown that many beneficial rhizosphere microbes can produce specific signaling molecules that affect plant root architecture and therefore could have substantial effects on above-ground growth. This review examines these chemical signals and summarizes their mechanisms of action, with the aim of enhancing our understanding of plant-microbe interactions and providing references for the comprehensive development and utilization of these active components in agricultural production. In addition, we highlight future research directions and challenges, such as searching for microbial signals to induce primary root development.

In Vivo Effect of Single Intra-Articular Injection of Tranexamic Acid on Articular Cartilage and Meniscus: Study in a Rat Model.

BACKGROUND: Tranexamic acid (TXA) has been increasingly used in arthroscopic surgery to prevent hemarthrosis. Despite its effectiveness, safety concerns have been raised regarding its potential cytotoxicity to articular cartilage and meniscus following intra-articular injection. METHODS: To evaluate the impact of TXA on cartilage and meniscus, a rat model of knee instability was utilized wherein anterior cruciate ligament (ACL) transection surgery was followed by a single intra-articular injection of TXA at varying concentrations (0, 20, 50, 100, and 150 mg/mL) in saline solution. Cell viability assessment of the cartilage and meniscus (n = 6 per group) was conducted at 24 hours, and gross observation and histological analysis of the medial tibial plateau and medial meniscus were conducted at 2, 4, and 8 weeks (n = 6 per group and time point). RESULTS: The chondrocyte viability was significantly decreased in the 50, 100, and 150 mg/mL TXA groups compared with the specimens injected with saline solution only (saline group) (p = 0.001, p < 0.001, p < 0.001, respectively), as was meniscal cell viability (p = 0.042, p < 0.001, p < 0.001, respectively). At week 8, the saline and 20 and 50 mg/mL groups showed relatively normal appearances, whereas the 100 and 150 mg/mL groups exhibited increased and varying severity of cartilage and meniscal degeneration. In the 150 mg/mL group, the mean Osteoarthritis Research Society International score was significantly higher than that in the saline and 20 mg/mL groups (p = 0.010 and p = 0.007). Additionally, the mean meniscus score in the 150 mg/mL group was significantly higher than that in the saline, 20 mg/mL, and 50 mg/mL groups (p = 0.020, p = 0.021, p = 0.031, respectively). CONCLUSIONS: Our findings indicate that concentrations of TXA at or above 100 mg/mL can lead to decreased cell viability in both cartilage and meniscus, resulting in significant cartilage degeneration in rats with ACL transection. Furthermore, the use of 150 mg/mL of TXA led to significant meniscal degeneration. CLINICAL RELEVANCE: It is prudent to avoid using concentrations of TXA at or above 100 mg/mL for intra-articular injection, as such concentrations may result in adverse effects on the cartilage and meniscus.

Anatomic characteristics of shoulder based on MRI accurately predict incomplete rotator cuff injuries in patients: relevance for predictive, preventive, and personalized healthcare strategies.

Background and PPPM-related working hypothesis: In the diagnosis of incomplete rotator cuff injuries (IRCI), magnetic resonance imaging (MRI) and ultrasound examination often have false-positive and false-negative results, while arthroscopy is expensive, invasive, and complex. From the strategy of predictive, preventive, and personalized medicine (PPPM), shoulder anatomical characteristics based on MRI have been demonstrated to accurately predict IRCI and their clinical applicability for personalized prediction of IRCI. Aims: This study aimed to develop and validate a nomogram based on anatomical features of the shoulder on MRI to identify IRCI for PPPM healthcare strategies. Methods: The medical information of 257 patients undergoing preoperative MRI examination was retrospectively reviewed and served as the primary cohort. Partial-thickness rotator cuff tears (RCTs) and tendinopathy observed under arthroscopy were considered IRCI. Using logistic regression analyses and least absolute shrinkage and selection operator (LASSO), IRCI was identified among various preoperative factors containing shoulder MRI and clinical features. A nomogram was constructed and subjected to internal and external validations (80 patients). Results: The following eight independent risk factors for IRCI were identified:AgeThe left injured sidesThe Goutallier classification of supraspinatus in oblique coronal positionThe Goutallier classification of supraspinatus in the axial positionAcromial thicknessAcromiohumeral distanceCoracohumeral distanceAbnormal acromioclavicular joint signalsThe nomogram accurately predicted IRCI in the development (C-index, 0.932 (95% CI, 0.891, 0.973)) and validation (C-index, 0.955 (95% CI, 0.918, 0.992)) cohorts. The calibration curve was consistent between the predicted IRCI probability and the actual IRCI ratio of the nomogram. The decision curve analysis and clinical impact curves demonstrated that the model had high clinical applicability. Conclusions: Eight independent factors that accurately predicted IRCI were determined using MRI anatomical findings. These personalized factors can prevent unnecessary diagnostic interventions (e.g., arthroscopy) and can assist surgeons in implementing individualized clinical decisions in medical practice, thus addressing the goals of PPPM. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00333-5.

Low-Dose Staphylococcal Enterotoxin C2 Mutant Maintains Bone Homeostasis via Regulating Crosstalk between Bone Formation and Host T-Cell Effector Immunity.

Studies in recent years have highlighted an elaborate crosstalk between T cells and bone cells, suggesting that T cells may be alternative therapeutic targets for the maintenance of bone homeostasis. Here, it is reported that systemic administration of low-dose staphylococcal enterotoxin C2 (SEC2) 2M-118, a form of mutant superantigen, dramatically alleviates ovariectomy (OVX)-induced bone loss via modulating T cells. Specially, SEC2 2M-118 treatment increases trabecular bone mass significantly via promoting bone formation in OVX mice. These beneficial effects are largely diminished in T-cell-deficient nude mice and can be rescued by T-cell reconstruction. Neutralizing assays determine interferon gamma (IFN-γ) as the key factor that mediates the beneficial effects of SEC2 2M-118 on bone. Mechanistic studies demonstrate that IFN-γ stimulates Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling, leading to enhanced production of nitric oxide, which further activates p38 mitogen-activated protein kinase (MAPK) and Runt-related transcription factor 2 (Runx2) signaling and promotes osteogenic differentiation. IFN-γ also directly inhibits osteoclast differentiation, but this effect is counteracted by proabsorptive factors tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß) secreted from IFN-γ-stimulated macrophages. Taken together, this work provides clues for developing innovative approaches which target T cells for the prevention and treatment of osteoporosis.

O-alg-THAM/gel hydrogels functionalized with engineered microspheres based on mesenchymal stem cell secretion recruit endogenous stem cells for cartilage repair.

Lacking self-repair abilities, injuries to articular cartilage can lead to cartilage degeneration and ultimately result in osteoarthritis. Tissue engineering based on functional bioactive scaffolds are emerging as promising approaches for articular cartilage regeneration and repair. Although the use of cell-laden scaffolds prior to implantation can regenerate and repair cartilage lesions to some extent, these approaches are still restricted by limited cell sources, excessive costs, risks of disease transmission and complex manufacturing practices. Acellular approaches through the recruitment of endogenous cells offer great promise for in situ articular cartilage regeneration. In this study, we propose an endogenous stem cell recruitment strategy for cartilage repair. Based on an injectable, adhesive and self-healable o-alg-THAM/gel hydrogel system as scaffolds and a biophysio-enhanced bioactive microspheres engineered based on hBMSCs secretion during chondrogenic differentiation as bioactive supplement, the as proposed functional material effectively and specifically recruit endogenous stem cells for cartilage repair, providing new insights into in situ articular cartilage regeneration.

Machine learning facilitating the rational design of nanozymes.

As a component substitute for natural enzymes, nanozymes have the advantages of easy synthesis, convenient modification, low cost, and high stability, and are widely used in many fields. However, their application is seriously restricted by the difficulty of rapidly creating high-performance nanozymes. The use of machine learning techniques to guide the rational design of nanozymes holds great promise to overcome this difficulty. In this review, we introduce the recent progress of machine learning in assisting the design of nanozymes. Particular attention is given to the successful strategies of machine learning in predicting the activity, selectivity, catalytic mechanisms, optimal structures and other features of nanozymes. The typical procedures and approaches for conducting machine learning in the study of nanozymes are also highlighted. Moreover, we discuss in detail the difficulties of machine learning methods in dealing with the redundant and chaotic nanozyme data and provide an outlook on the future application of machine learning in the nanozyme field. We hope that this review will serve as a useful handbook for researchers in related fields and promote the utilization of machine learning in nanozyme rational design and related topics.

Long Non-Coding RNA Malat1 Increases the Rescuing Effect of Quercetin on TNFα-Impaired Bone Marrow Stem Cell Osteogenesis and Ovariectomy-Induced Osteoporosis.

Osteoporosis, a common systematic bone homeostasis disorder related disease, still urgently needs innovative treatment methods. Several natural small molecules were found to be effective therapeutics in osteoporosis. In the present study, quercetin was screened out from a library of natural small molecular compounds by a dual luciferase reporter system. Quercetin was found to upregulate Wnt/ß-catenin while inhibiting NF-κB signaling activities, and thereby rescuing osteoporosis-induced tumor necrosis factor alpha (TNFα) impaired BMSCs osteogenesis. Furthermore, a putative functional lncRNA, Malat1, was shown to be a key mediator in quercetin regulated signaling activities and TNFα-impaired BMSCs osteogenesis, as mentioned above. In an ovariectomy (OVX)-induced osteoporosis mouse model, quercetin administration could significantly rescue OVX-induced bone loss and structure deterioration. Serum levels of Malat1 were also obviously rescued in the OVX model after quercetin treatment. In conclusion, our study demonstrated that quercetin could rescue TNFα-impaired BMSCs osteogenesis in vitro and osteoporosis-induced bone loss in vivo, in a Malat1-dependent manner, suggesting that quercetin may serve as a therapeutic candidate for osteoporosis treatment.

Enhancing cartilage repair with optimized supramolecular hydrogel-based scaffold and pulsed electromagnetic field.

Functional tissue engineering strategies provide innovative approach for the repair and regeneration of damaged cartilage. Hydrogel is widely used because it could provide rapid defect filling and proper structure support, and is biocompatible for cell aggregation and matrix deposition. Efforts have been made to seek suitable scaffolds for cartilage tissue engineering. Here Alg-DA/Ac-ß-CD/gelatin hydrogel was designed with the features of physical and chemical multiple crosslinking and self-healing properties. Gelation time, swelling ratio, biodegradability and biocompatibility of the hydrogels were systematically characterized, and the injectable self-healing adhesive hydrogel were demonstrated to exhibit ideal properties for cartilage repair. Furthermore, the new hydrogel design introduces a pre-gel state before photo-crosslinking, where increased viscosity and decreased fluidity allow the gel to remain in a semi-solid condition. This granted multiple administration routes to the hydrogels, which brings hydrogels the ability to adapt to complex clinical situations. Pulsed electromagnetic fields (PEMF) have been recognized as a promising solution to various health problems owing to their noninvasive properties and therapeutic potentials. PEMF treatment offers a better clinical outcome with fewer, if any, side effects, and wildly used in musculoskeletal tissue repair. Thereby we propose PEMF as an effective biophysical stimulation to be 4th key element in cartilage tissue engineering. In this study, the as-prepared Alg-DA/Ac-ß-CD/gelatin hydrogels were utilized in the rat osteochondral defect model, and the potential application of PEMF in cartilage tissue engineering were investigated. PEMF treatment were proven to enhance the quality of engineered chondrogenic constructs in vitro, and facilitate chondrogenesis and cartilage repair in vivo. All of the results suggested that with the injectable self-healing adhesive hydrogel and PEMF treatment, this newly proposed tissue engineering strategy revealed superior clinical potential for cartilage defect treatment.

Long-term follow-up of Janus-kinase inhibitor and novel active disease biomarker in juvenile dermatomyositis.

OBJECTIVE: To evaluate the use of Janus kinase inhibitor (JAKi) in treating JDM and develop cytokine biomarkers of active disease. METHODS: This study involved a retrospective cohort study that evaluated JAKi in 101 JDM patients as well as a cross-sectional study of cytokines in 128 JDM patients and 30 controls between November 2017 and December 2021 in the Affiliated Children's Hospital of Capital Institute of Pediatrics (China). RESULTS: During the median follow-up period of 19 months, 65.5% of the patients had improved rashes, and CAT-BM scores decreased. Overall, 39.6% of JDM patients eliminated glucocorticoids. Muscle strength was improved in all patients who had abnormal muscle strength before JAKi use. Patients and parents provided positive subjective reviews of JAKi, and no serious adverse events were reported. Potential side effects of JAKi included abnormal leukopoenia (14/95) and cough (16/83), which affected over 10% of the JDM patients. In the cytokine analysis, 12/34 cytokines were significantly elevated in active JDM patients. Compared with active JDM patients with multiple phenotypes, active JDM patients with only rashes demonstrated lower cytokine levels. Anti-NXP2-positive active patients had lower cytokine levels compared with those without positive anti-NXP2 antibodies. Among all increased cytokines, IL-1RA changed most dramatically, reaching over 793 times the mean of normal values. We developed a panel composed of six cytokines to differentiate active or stable status in our cohort (area under the curve = 0.8486, P < 0.05). CONCLUSION: The preliminary evidence suggested that JAKi is a relatively safe and effective alternative for JDM patients. Cytokine profiles could well reflect the inflammatory status of JDM patients.

Lattice Boltzmann Simulation of Coupling Heat Transfer between Solid and Gas Phases of Nanoporous Materials.

In order to deeply study the heat conduction of nanoporous aerogel, a model of gas-solid heat conduction was established based on the microstructure of aerogel. The model was divided into two subdomains with uniform mesh because of the different gas-solid characteristics, and simulation was performed on each domain using the lattice Boltzmann method. The value of temperature on the boundaries of subdomains was determined by interpolation. Finally, the temperature distribution and the thermal conductivity were maintained. It can be concluded that when the gas-phase scale was fixed, the temperature distribution of the solid phase became more uniform when the scale increased; when the solid-phase scale was fixed, the temperature jump on the gas-solid interface decreased with the increase in the gas-phase scale; and the thermal conductivity of gas-solid coupling varied with the scale of the gas phase or solid phase, showing a scale effect in varying degrees.

Coacervate-Derived Hydrogel with Effective Water Repulsion and Robust Underwater Bioadhesion Promotes Wound Healing.

Achieving robust underwater adhesion by bioadhesives remains a challenge due to interfacial water. Herein a coacervate-to-hydrogel strategy to enhance interfacial water repulsion and bulk adhesion of bioadhesives is reported. The polyethyleneimine/thioctic acid (PEI/TA) coacervate is deposited onto underwater substrates, which can effectively repel interfacial water and completely spread into substrate surface irregularities due to its liquid and water-immiscible nature. The physical interactions between coacervate and substrate can further enhance interfacial adhesion. Furthermore, driven by the spontaneous hydrophobic aggregation of TA molecules and strong electrostatic interaction between PEI and TA, the coacervate can turn into a hydrogel in situ within minutes without additional stimuli to develop enhanced matrix cohesion and robust bulk adhesion on diverse underwater substrates. Molecular dynamics simulations further reveal atomistic details of the formation and wet adhesion of the PEI/TA coacervate via multimode physical interactions. Lastly, it is demonstrated that the PEI/TA coacervate-derived hydrogel can effectively repel blood and therefore efficiently deliver the carried growth factors at wound sites, thereby enhancing wound healing in an animal model. The advantages of the PEI/TA coacervate-derived hydrogel including body fluid-immiscibility, strong underwater adhesion, adaptability to fit irregular target sites, and excellent biocompatibility make it a promising bioadhesive for diverse biomedical applications.

One-stop molecular classification of endometrial carcinoma using comprehensive next-generation sequencing.

This study aims to investigate the feasibility of molecular classification using only comprehensive next-generation sequencing-based techniques and its relationship with survival outcomes in patients with endometrial cancer. Paired tumor-normal sequencing data of 1021 cancer-related genes using tumor tissues or peripheral blood samples and clinical data were retrospectively collected from a cohort of endometrial cancers. The microsatellite instability status was inferred using the MSIsensor (v0.5) with a cut-off of 8%. Sixty patients were classified into four groups: POLEMUT group (13.3%), MSI-H group (20%), TP53WT group (45%) and TP53MUT group (21.7%). Patients within TP53MUT group were more common in serous carcinoma compared to endometrioid carcinoma (P = .0098). TP53WT was significantly correlated with early stage and low grade. TP53MUT group was associated with significantly worse DFS compared to MSI-H group and TP53WT group (P = .014 and .004, respectively). Comprehensive next-generation sequencing is a reliable and simple method to stratify the prognosis of endometrial carcinoma. It can be potentially used to guide treatment of patients with endometrial cancer in routine practice.

Malat1 attenuated the rescuing effects of docosahexaenoic acid on osteoarthritis treatment via repressing its chondroprotective and chondrogenesis activities.

Osteoarthritis (OA) is a degenerative disease associated with joint inflammation, articular cartilage degeneration and subchondral hypertrophy. Small molecules which both ameliorate chondrocyte OA phenotype and activate bone marrow-derived mesenchymal stem cells (BMSCs) chondrogenesis under inflammatory conditions have the therapeutical potential for OA treatment. In this study, we characterized a novel small molecule which could ameliorate OA progression via novel regulating mechanisms. Docosahexaenoic acid (DHA), a bioactive molecule, was screened from a small molecule library and showed anti-inflammatory and chondroprotective effects in OA chondrocytes, as well as ameliorated IL-1ß impaired BMSCs chondrogenesis in Wnt/ß-catenin and NF-κB signaling dependent manners. Furthermore, Malat1 was found to be the key mediator of DHA-mediating anti-inflammation chondroprotection and chondrogenesis. DHA also rescued cartilage loss and damage in a surgery-induced OA mice model. The elevation of serum Malat1 levels caused by OA was also downregulated by DHA treatment. Taken together, our findings demonstrated that DHA, with a dual-signaling repression property, exerted its anti-inflammation, chondroprotection and chondrogenesis function possibly via regulating Malat1 level, suggesting that it may be a possible drug candidate for OA patients with elevated MALAT1 expression levels.