A comparative full-length transcriptomic resource provides insight into the perennial monocarpic mass flowering.

Perennial monocarpic mass flowering represents as a key developmental innovation in flowering time diversity in several biological and economical essential families, such as the woody bamboos and the shrubby Strobilanthes. However, molecular and genetic mechanisms underlying this important biodiversity remain poorly investigated. Here, we generated a full-length transcriptome resource incorporated into the BlueOmics database (http://blueomics.iflora.cn) for two Strobilanthes species, which feature contrasting flowering time behaviors. Using about 112 and 104 Gb Iso-seq reads together with ~185 and ~75 Gb strand-specific RNA seq data, we annotated 80 971 and 79 985 non-redundant full-length transcripts for the perennial polycarpic Strobilanthes tetrasperma and the perennial monocarpic Strobilanthes biocullata, respectively. In S. tetrasperma, we identified 8794 transcripts showing spatiotemporal expression in nine tissues. In leaves and shoot apical meristems at two developmental stages, 977 and 1121 transcripts were differentially accumulated in S. tetrasperma and S. biocullata, respectively. Interestingly, among the 33 transcription factors showing differential expression in S. tetrasperma but without differential expression in S. biocullata, three were involved potentially in the photoperiod and circadian-clock pathway of flowering time regulation (FAR1 RELATED SEQUENCE 12, FRS12; NUCLEAR FACTOR Y A1, NFYA1; PSEUDO-RESPONSE REGULATOR 5, PRR5), hence provides an important clue in deciphering the flowering diversity mechanisms. Our data serve as a key resource for further dissection of molecular and genetic mechanisms underpinning key biological innovations, here, the perennial monocarpic mass flowering.

Transcending membrane barriers: advances in membrane engineering to enhance the production capacity of microbial cell factories.

Microbial cell factories serve as pivotal platforms for the production of high-value natural products, which tend to accumulate on the cell membrane due to their hydrophobic properties. However, the limited space of the cell membrane presents a bottleneck for the accumulation of these products. To enhance the production of intracellular natural products and alleviate the burden on the cell membrane caused by product accumulation, researchers have implemented various membrane engineering strategies. These strategies involve modifying the membrane components and structures of microbial cell factories to achieve efficient accumulation of target products. This review summarizes recent advances in the application of membrane engineering technologies in microbial cell factories, providing case studies involving Escherichia coli and yeast. Through these strategies, researchers have not only improved the tolerance of cells but also optimized intracellular storage space, significantly enhancing the production efficiency of natural products. This article aims to provide scientific evidence and references for further enhancing the efficiency of similar cell factories.

Critical steps in the restoration of coal mine soils: Microbial-accelerated soil reconstruction.

Soil reconstruction is a critical step in the restoration of environments affected by mining activities. This paper provides a comprehensive review of the significant role that microbial processes play in expediting soil structure formation, particularly within the context of mining environment restoration. Coal gangue and flotation tailings, despite their low carbon content and large production volumes, present potential substrates for soil reclamation. These coal-based solid waste materials can be utilized as substrates to produce high-quality soil and serve as an essential carbon source to enhance poor soil conditions. However, extracting active organic carbon components from coal-based solid waste presents a significant challenge due to its complex mineral composition. This article offers a thorough review of the soilization process of coal-based solid waste under the influence of microorganisms. It begins by briefly introducing the primary role of in situ microbial remediation technology in the soilization process. It then elaborates on various improvements to soil structure under the influence of microorganisms, including the enhancement of soil aggregate structure and soil nutrients. The article concludes with future recommendations aimed at improving the efficiency of soil reconstruction and restoration, reducing environmental risks, and promoting its application in complex environments. This will provide both theoretical and practical support for more effective environmental restoration strategies.

The nuclear receptor subfamily 4 group A1 in human disease.

Nuclear receptor 4A1 (NR4A1), a member of the NR4A subfamily, acts as a gene regulator in a wide range of signaling pathways and responses to human diseases. Here, we provide a brief overview of the current functions of NR4A1 in human diseases and the factors involved in its function. A deeper understanding of these mechanisms can potentially improve drug development and disease therapy.

Structural definition of the discrete hotspot sites of BMP-2 conformational wrist epitope and rational design of the hotspot-derived osteogenic peptides against chondrocyte senescence.

The bone morphogenetic protein-2 (BMP-2) is an essential regulator of bone formation and remodeling, which has also been implicated in the pathogenesis of osteoarthritis and its closely related chondrocyte senescence. The BMP-2 uses a conformational wrist epitope and a linear knuckle epitope to interact with type-I (BMPR-I) and type-II (BMPR-II) receptors, respectively. Previously, the knuckle epitope has been intensely studied, but the wrist epitope still remains largely unexplored due to its discontinuous nature. In the present work, the intermolecular interaction of BMP-2 with BMPR-I was investigated systematically at structural, energetic and dynamic levels. Three discrete hotspots that represent the key BMPR-I recognition sites of BMP-2 were identified; they are spatially dispersed over the two monomers of BMP-2 dimer and totally account for 83.5 % binding potency of BMP-2 to BMPR-I (hotspot 1: residues 49-70 in monomer 1; hotspot 2: residues 24-31 in monomer 2; hotspot 3: residues 88-107 in monomer 2). Therefore, we defined the three discrete hotspot sites as the core region of wrist epitope; their contribution to the binding increases in the order: hotspot 2 < hotspot 3 < hotspot 1. We demonstrated that the primary hotspot 1 site has a native U-shaped conformation in the full-length BMP-2 protein context, but it cannot maintain in the native conformation when split from the context to obtain a free hotspot-1 peptide, thus largely impairing its binding potency to BMPR-I. We further employed disulfide-bonded cyclization and head-to-tail cyclization to constrain the peptide conformation, and found that only the former can effectively constrain the peptide into native conformation, thus considerably improving its binding affinity to BMPR-I, whereas the latter totally disorders the native conformation, thus rendering the peptide as a full nonbinder of BMPR-I.

Synthetic Homogeneous Glycoforms of the SARS-CoV-2 Spike Receptor-Binding Domain Reveals Different Binding Profiles of Monoclonal Antibodies.

SARS-CoV-2 attaches to its host receptor, angiotensin-converting enzyme 2 (ACE2), via the receptor-binding domain (RBD) of the spike protein. The RBD glycoprotein is a critical target for the development of neutralizing antibodies and vaccines against SARS-CoV-2. However, the high heterogeneity of RBD glycoforms may lead to an incomplete neutralization effect and impact the immunogenic integrity of RBD-based vaccines. Investigating the role of different carbohydrate domains is of paramount importance. Unfortunately, there is no viable method for preparing RBD glycoproteins with structurally defined glycans. Herein we describe a highly efficient and scalable strategy for the preparation of six glycosylated RBDs bearing defined structure glycoforms at T323, N331, and N343. A combination of modern oligosaccharide, peptide synthesis and recombinant protein engineering provides a robust route to decipher carbohydrate structure-function relationships.

Effect of disease duration on functional outcomes and complications after arthrolysis in patients with elbow stiffness.

HYPOTHESIS: The purpose of this study was to determine the effect of a long duration of elbow stiffness on functional outcomes and complications after arthrolysis. METHODS: Participants included consecutive patients with a long duration of elbow stiffness (≥5 years, n = 23) and control patients matched for age, sex, and initial injury type (n = 46). All patients underwent elbow arthrolysis combined with hinged external fixation between March 2014 and March 2016. At baseline and follow-up, we evaluated elbow motion (flexion, extension, supination, pronation, and range of motion) and patient-reported outcomes, including the Mayo Elbow Performance Score (MEPS) and visual analog scale for pain. Postoperative complications including infection, nerve dysfunction, and instability were recorded. RESULTS: There were no significant differences in preoperative elbow pain, range of motion, or MEPS between groups. Postoperatively, pronation and the MEPS in patients with a long disease duration were inferior to those in control patients (P = .041 and P = .016, respectively). Patients with a long disease duration also had a significantly higher incidence of complications than control patients (P = .002). At final follow-up, 7 patients (30%) in the long disease duration group and 3 patients (7%) in the control group presented with nerve symptoms (P = .022). CONCLUSIONS: A long duration of elbow stiffness may negatively influence functional outcomes and increase the risk of complications after arthrolysis.

Risk factors for development of severe post-traumatic elbow stiffness.

PURPOSE: The purpose of this study was to compare different grades of elbow stiffness and investigate demographic, injury, and treatment factors potentially associated with the development of severe elbow stiffness. METHODS: We performed a retrospective study involving 169 patients with post-traumatic elbow stiffness between June 2014 and June 2016. Patient demographics, injury, and treatment details were reviewed. Patients were classified into three groups according to the elbow motion. Ordinal regression analyses were performed to examine the independent factors. RESULTS: Patients were classified into: mild (49 patients), moderate (59 patients), and severe (61 patients) groups. Patients with severe stiffness had a significantly worse elbow functional performance. Univariate ordinal regression revealed that severe elbow stiffness was associated with high-energy injury (odds ratio [OR] 4.73), olecranon fracture (OR 1.92), fracture-dislocation (OR 2.28), and open fracture (OR 3.24). Multivariate regression showed that higher-energy injuries were associated with severe stiffness (OR 4.45, p = 0.003). CONCLUSIONS: Elbow stiffness after fracture surgery often results in joint stiffness. Severe stiffness often resulted in more significant functional impairment. Our study suggested that high-energy injuries were associated with the development of severe elbow stiffness.

Management of elbow stiffness after postoperative treatment of terrible triad elbow injury: maintaining mobility and stability using a combined protocol.

PURPOSES: The purpose of this study was to evaluate the results of our protocol that include the restoration of mobility using open release combined with external fixation and stability using ligament repair, to determine the optimal timing of surgery, and to investigate whether resection and replacement of the radial head are associated with different outcomes. METHODS: Twenty-six patients with elbow stiffness after operation of terrible triad injury of the elbow were treated with our protocol. We assessed the optimal timing of the operation by comparing outcomes between the early treatment group and the delayed treatment group. The comparison was performed to investigate whether the results differed between resection and replacement of the radial head. Stability of the elbow, range of motion (ROM), Mayo Elbow Performance Score (MEPS), and complications were assessed for each patient. RESULTS: The mean interval from the initial surgery to the index procedure was 13 months, and the mean follow-up period was 29 months. The MEPS increased from a mean of 65 points to 94 points. Twenty-five of 26 patients achieved stability of the elbow, and all patients achieved functional ROM. There were no significant differences between the two subgroups with respect to ROM and stability of the elbow. CONCLUSION: Our protocol can restore mobility and stability. Resection and replacement of the radial head are both feasible using this protocol. Lastly, the timing of the surgery was not very rigorous, and the surgical delay may be insignificant. LEVEL OF EVIDENCE: Level IV; Case Series; Treatment Study.

The influence of body mass index on outcome of open arthrolysis for post-traumatic elbow stiffness.

BACKGROUND: Being overweight has become a serious public health concern in China. Higher body mass index has been proven to be associated with poor outcome after orthopedic surgery. The purpose of this study was to examine the effect of being overweight on functional outcomes and complications after open arthrolysis for post-traumatic elbow stiffness. METHODS: We performed a retrospective study including 122 patients with post-traumatic elbow stiffness undergoing arthrolysis, including 84 in the normal weight group and 38 in the overweight group. Demographic data, surgical data, and data on preoperative and postoperative functional performance and complications were obtained. RESULTS: Demographic data and disease characteristics were comparable between the 2 groups at baseline. All patients showed significant improvement after elbow arthrolysis. Postoperatively, the range of motion and Mayo Elbow Performance Score of the normal weight group were significantly better than those of the overweight group. Sixteen patients developed postoperative complications. No significant differences in complication rates between the 2 groups were found. CONCLUSIONS: Most patients showed satisfactory functional outcomes after arthrolysis. The postoperative functional outcomes of the overweight group were inferior to those of the normal weight group to a certain extent. This study underlines the importance of detailed rehabilitation instructions in patients with higher body mass index.

Results and outcome predictors after open release of complete ankylosis of the elbow caused by heterotopic ossification.

BACKGROUND: Heterotopic ossification (HO) may lead to complete elbow ankylosis, resulting in severe disability. The prognostic factors that may be valuable in guiding treatment of this condition have not yet been evaluated. The goals of this study were to describe the outcomes of open release for ankylosed elbow caused by HO and to analyse factors associated with clinical outcomes. METHOD: This retrospective study assessed 41 patients with ankylosed elbows treated by open release surgery. We report final clinical outcomes and analyses of the association between outcomes and clinical variables. RESULTS: Mean patient age was 36.4 years; follow-up was 36.1 months. Mean arc of motion increased from 0 to 112° post-operatively, mean pronation from 34 to 52°, supination from a mean of 51 to 76°, and Mean Mayo Elbow Performance Score (MEPS) from 42.8 to 84.2. Eight patients experienced recurrence, two of whom underwent a second operation: one for elbow instability and one for revision surgery. Linear regression analysis demonstrated that initial injury type (p = 0.020), articular surface damage (p = 0.001), coma iduringthe initial injury (p = 0.001) and concomitant radial head replacement (p = 0.029) were independent factors affecting the final MEPS. CONCLUSIONS: Satisfactory outcomes were achieved, indicating that open release is effective for ankylosed elbows. Our findings demonstrated that initial injury type, articular surface damage, coma and radial head replacement are outcome predictors affecting final outcomes.

Losartan ameliorates renal fibrosis by inhibiting tumor necrosis factor signal pathway.

Losartan is widely used in the treatment of chronic kidney disease (CKD) and has achieved good clinical efficacy, but its exact mechanism is not clear. We performed high-throughput sequencing (HTS) technology to screen the potential target of losartan in treating CKD. According to the HTS results, we found that the tumor necrosis factor (TNF) signal pathway was enriched. Therefore, we conducted in vivo and in vitro experiments to verify it. We found that TNF signal pathway was activated in both unilateral ureteral obstruction (UUO) rats and human proximal renal tubular epithelial cells (HK-2) treated with transforming growth factor-ß1 (TGF-ß1), while losartan can significantly inhibit TNF signal pathway as well as the expression of fibrosis related genes (such as COL-1, α-SMA and Vimentin). These data suggest that losartan may ameliorate renal fibrosis through modulating the TNF pathway.

The role of PI3K/Akt signaling pathway in chronic kidney disease.

Chronic kidney disease (CKD), including chronic glomerulonephritis, IgA nephropathy and diabetic nephropathy, are common chronic diseases characterized by structural damage and functional decline of the kidneys. The current treatment of CKD is symptom relief. Several studies have reported that the phosphatidylinositol 3 kinases (PI3K)/protein kinase B (Akt) signaling pathway is a pathway closely related to the pathological process of CKD. It can ameliorate kidney damage by inhibiting this signal pathway which is involved with inflammation, oxidative stress, cell apoptosis, epithelial mesenchymal transformation (EMT) and autophagy. This review highlights the role of activating or inhibiting the PI3K/Akt signaling pathway in CKD-induced inflammatory response, apoptosis, autophagy and EMT. We also summarize the latest evidence on treating CKD by targeting the PI3K/Akt pathway, discuss the shortcomings and deficiencies of PI3K/Akt research in the field of CKD, and identify potential challenges in developing these clinical therapeutic CKD strategies, and provide appropriate solutions.

The roles of orphan nuclear receptor 4 group A1 and A2 in fibrosis.

Fibrosis is not a disease but rather an outcome of the pathological tissue repair response. Many myofibroblasts are activated which lead to the excessive accumulation of extracellular matrix components such as collagen and fibronectin with fibrosis. A variety of organs, including kidney, liver, lung, heart and skin, can undergo fibrosis under the stimulation of exogenous or endogenous pathogenic factors. The orphan nuclear receptor 4 group A1 (NR4A1) and nuclear receptor 4 group A2（NR4A2）are belong to the nuclear receptor subfamily and inhibit the occurrence and development of fibrosis. NR4A1 is an inhibitory factor of TGF-ß signaling transduction. Overexpression of NR4A1 in fibroblasts can reduce TGF-ß induced collagen deposition and fibrosis related gene expression. Here, we summarize the current research progress on the NR4A1/2 and fibrosis, providing reference for the treatment of fibrosis.

Nuclear receptor 4A1 ameliorates renal fibrosis by inhibiting vascular endothelial growth factor A induced angiogenesis in UUO rats.

INTRODUCTION: Angiogenesis is closely related to renal fibrosis; however, its basic mechanism remains unclear. In our study, we found that nuclear receptor 4A1 (NR4A1) inhibits vascular endothelial growth factor A (VEGFA)-induced angiogenesis, ameliorating renal fibrosis. METHODS: We prepared a renal fibrosis animal model with unilateral ureteral obstruction (UUO) and NR4A1 knockdown UUO mice model, Using Human umbilical vein endothelial cells (HUVECs) to conduct all in vitro experiments. We then detected and analyzed the expression levels of NR4A1 and other genes related to angiogenesis and fibrosis. RESULTS: The angiogenesis related genes, such as VEGFA, vascular endothelial growth factor receptor-2 (VEGFR-2), endoglin (CD105), as well as the expression of fibrosis related genes that included, α-smooth muscle actin (α-SMA), Vimentin, and Collagen I are all significantly increased in the UUO rat model. In addition, the expression of NR4A1 of the kidney tissue of UUO rats was significantly reduced. Therefore, according to the above results, we speculated that angiogenesis may exacerbate renal fibrosis and NR4A1 may repress renal fibrosis by inhibiting angiogenesis. To further verify the above results, we used VEGFA to stimulate HUVECs with (or without) overexpression or knockdown of NR4A1. The results showed that with prolonged stimulation using VEGFA, the expression of NR4A1 decreases. Overexpression of NR4A1 significantly inhibits the expression of related indicators of angiogenesis and renal fibrosis. Furthermore, knockdown of NR4A1 induces endothelial cell proliferation and migration; therefore, exacerbating angiogenesis and fibrosis. Finally, the results of NR4A1 knockdown UUO mice showed that knockdown of NR4A1 can aggravating kidney damage and induce the expression of angiogenesis and renal fibrosis related indicators, while UUO can significantly induce kidney damage, angiogenesis and renal fibrosis. When knockdown of NR4A1, renal kidney damage, angiogenesis and fibrosis becomes more severe than UUO. Thus, all of these results indicate that NR4A1 can ameliorate renal fibrosis by inhibiting angiogenesis. CONCLUSIONS: NR4A1 can inhibit angiogenesis to ameliorate renal fibrosis.

Coal slime as a good modifier for the restoration of copper tailings with improved soil properties and microbial function.

In recent years, the solid wastes from the coal industry have been widely used as soil amendments. Nevertheless, the impact of utilizing coal slime for copper tailing restoration in terms of plant growth, physicochemical characteristics of the tailing soil, and microbial succession remains uncertain.Herein, the coal slime was employed as a modifier into copper tailings. Their effect on the growth and physiological response of Ryegrass, and the soil physicochemical properties as well as the bacterial community structure were investigated. The results indicated that after a 30-day of restoration, the addition of coal slime at a ratio of 40% enhanced plant growth, with a 21.69% rise in chlorophyll content, and a 62.44% increase in peroxidase activity. The addition of 40% coal slime also increased the content of nutrient elements in copper tailings. Following a 20-day period of restoration, the concentrations of available copper and available zinc in the modified tailings decreased by 39.6% and 48.51%, respectively, with 40% of coal slime added. In the meantime, there was an observed augmentation in the species diversity of the bacterial community in the modified tailings. The alterations in both community structure and function were primarily influenced by variations in pH value, available nitrogen, phosphorus, potassium, and available copper. The addition of 40% coal slime makes the physicochemical properties and microbial community evolution of copper tailings reach a balance point. The utilization of coal slime has the potential to enhance the physicochemical characteristics of tailings and promote the proliferation of microbial communities, hence facilitating the soil evolution of two distinct solid waste materials. Consequently, the application of coal slime in the restoration of heavy metal tailings is a viable approach, offering both cost-effectiveness and efficacy as an enhancer.

Fatigue life prediction of brake discs for high-speed trains via thermal stress.

As one of the essential components of the braking system, the high-speed train brake disc is an integral part of ensuring the safety of the train. The main objective of this study is to conduct thermal analysis and reliable life prediction on brake discs. The research was conducted by developing a programmer spectrum of brake discs with high-speed train brake discs. According to the results of numerical analysis and the S-N curve of the material, the temperature distribution on the surface of the brake disc is determined, and the fatigue life of the brake disc is predicted. The comparison with the service life of the brake disc verifies the rationality of the calculation results. In addition, a fatigue damage probability model of brake discs is established based on the theory of fatigue cumulative damage. Through the relationship between the reliability of mechanical parts and the number of load cycles, the reliable life of the brake disc under different working conditions is predicted. This work establishes a method of reliable life analysis for brake discs of high-speed trains based on the load spectrum, which could analyze the life and reliability of brake discs more systematically.

MiR-20a-5p facilitates cartilage repair in osteoarthritis via suppressing mitogen-activated protein kinase kinase kinase 2.

Bone marrow mesenchymal stem cell (BMSC) chondrogenic differentiation contributes to the treatment of osteoarthritis (OA). Numerous studies have indicated that microRNAs (miRNAs) regulate the pathogenesis and development of multiple disorders, including OA. Nevertheless, the role of miR-20a-5p in OA remains obscure. Forty male C57BL/6 mice were divided into four groups and were surgically induced OA or underwent sham surgery in the presence or absence of miR-20a-5p. Flow cytometry was implemented to detect surface markers of BMSCs. Reverse transcription quantitative polymerase chain reaction revealed the upregulation of miR-20a-5p during BMSC chondrogenic differentiation. Western blotting displayed that miR-20a-5p inhibition decreased protein levels of cartilage matrix markers but enhanced those of catabolic and hypertrophic chondrocyte markers in BMSCs. Alcian blue staining, hematoxylin­eosin staining and micro-CT revealed that miR-20a-5p inhibition restrained chondrogenic differentiation and miR-20a-5p overexpression promoted the repair of damaged cartilage and subchondral bone, respectively. Luciferase reporter assay identified that mitogen activated protein kinase kinase kinase 2 (Map3k2) was a target of miR-20a-5p in BMSCs. Moreover, the expression of miR-20a-5p and Map3k2 was negatively correlated in murine cartilage tissues. Knocking down Map3k2 could rescue the suppressive influence of miR-20a-5p inhibition on chondrogenic differentiation of BMSCs. In conclusion, miR-20a-5p facilitates BMSC chondrogenic differentiation and contributes to cartilage repair in OA by suppressing Map3k2.

Clinical results of a 10-year follow-up of surgical treatment for elbow stiffness in rheumatoid arthritis: A case series.

BACKGROUND: Rheumatoid arthritis commonly causes transient limitation of joint motion, but the treatment of persistent stiffness in the rheumatoid elbow has rarely been reported. The purpose of this study was to evaluate the long-term clinical results of surgical treatment of rheumatoid elbow stiffness. METHODS: Surgical treatment, including open arthrolysis with hinged external fixation, total synovectomy, and ulnar nerve release and anteriorization, was performed in 48 elbows in 43 patients with rheumatoid arthritis and early joint destruction. Mobility (flexion-extension and pronation-supination), Mayo Elbow Performance Score (MEPS), visual analog scale (VAS) score, muscle strength, nerve symptoms, postoperative complications, and recurrent synovitis were evaluated 9-11 years (average, 9.88 years) postoperatively. RESULTS: The mobility of the elbow was significantly improved over the preoperative period either in extension, flexion, protonation, supination (P < .001, P < .001, P < .001, P = .002). The mean MEPS was significantly improved from 56.25 points (range, 30-90) to 87.40 points (range, 40-100) (P < .001). The pain was relieved, and the mean VAS score was reduced from 3.56 (range, 0-8) to 1.08 (range, 0-5) points (P < .001). Preoperative ulnar nerve symptoms were observed in 17 patients and relieved in 10 (59%) patients, and the mean Amadio score was raised from 6.9 (range, 3-9) to 7.96 (range, 4-9) points (P < .001). Through surgical treatment and postoperative rehabilitation, the mean grip strength of the patients was significantly improved from an average of 9.01 (range, 3.4-18.5) to 17.56 kg (range, 3.9-40.2) (P < .001). Five elbows developed recurrent synovitis, and one underwent total elbow arthroplasty. Postoperative complications were uncommon and not severe. CONCLUSION: Surgical treatment is a reliable procedure for rheumatoid elbow stiffness and can be effective in improving elbow mobility, function, muscle strength, pain relief, and relief of nerve symptoms.

Machine learning-guided evolution of BMP-2 knuckle Epitope-Derived osteogenic peptides to target BMP receptor II.

Bone morphogenetic protein-2 (BMP-2) is a key regulator of bone formation, growth and regeneration, which contains a conformational wrist epitope and a linear knuckle epitope that are functionally responsible for the protein by mediating its interaction with type-I and type-II receptors, respectively. Previously, a long (19-mer) knuckle peptide derived from the knuckle epitope region (residues 73-92) has been found to promote osteogenesis and bone repair. Here, we attempt to rationally redesign the knuckle peptide by using bioinformatics and machine learning-guided evolution to obtain structurally simplified, potent osteogenic peptides that are capable of targeting type-II receptor. Complex analysis reveals that only a fraction of the epitope region can directly interact with type-II receptor, which represents a small (12-mer) knuckle-derived peptide (KDP0 peptide). Glycine scanning further identifies three KDP0 anchor residues Ser88, Leu90 and Tyr91 that are fundamentally important in the peptide-receptor binding. Systematic mutation, amino acid combination and uniform design of other nine KDP0 non-anchor residues generate 32 new knuckle-derived peptides (KDP1-KDP32); their binding affinities to recombinant protein of human type-II receptor are determined using fluorescence spectroscopy assay. The resulting affinity values (Kd) are used to train six regression models developed by combination of two machine learning methods and three amino acids descriptors. The best SVM/VHSE predictor is then utilised to guide the genetic evolution of a knuckle-derived peptide population. Eight peptides (KDP33-KDP40) with high affinity scores are selected from the improved population, and their osteogenic activities on bone marrow stromal cells are measured using alkaline phosphatase assay. Consequently, six out of the 8 tested peptides exhibit increased activity relative to KDP0 peptide. The KDP34 (DFQTWSFLYVEN) is found as the most potent peptide with APL activities of 195% and 279% at 0.01 and 0.1 µg/ml, respectively, which shares a similar binding mode with the native knuckle epitope and can form diverse nonbonded interactions of hydrogen bond, hydrophobic contact, cation-π/π-π stacking and salt bridge with type-II receptor.