DeepPBI-KG: a deep learning method for the prediction of phage-bacteria interactions based on key genes.

Phages, the natural predators of bacteria, were discovered more than 100 years ago. However, increasing antimicrobial resistance rates have revitalized phage research. Methods that are more time-consuming and efficient than wet-laboratory experiments are needed to help screen phages quickly for therapeutic use. Traditional computational methods usually ignore the fact that phage-bacteria interactions are achieved by key genes and proteins. Methods for intraspecific prediction are rare since almost all existing methods consider only interactions at the species and genus levels. Moreover, most strains in existing databases contain only partial genome information because whole-genome information for species is difficult to obtain. Here, we propose a new approach for interaction prediction by constructing new features from key genes and proteins via the application of K-means sampling to select high-quality negative samples for prediction. Finally, we develop DeepPBI-KG, a corresponding prediction tool based on feature selection and a deep neural network. The results show that the average area under the curve for prediction reached 0.93 for each strain, and the overall AUC and area under the precision-recall curve reached 0.89 and 0.92, respectively, on the independent test set; these values are greater than those of other existing prediction tools. The forward and reverse validation results indicate that key genes and key proteins regulate and influence the interaction, which supports the reliability of the model. In addition, intraspecific prediction experiments based on Klebsiella pneumoniae data demonstrate the potential applicability of DeepPBI-KG for intraspecific prediction. In summary, the feature engineering and interaction prediction approaches proposed in this study can effectively improve the robustness and stability of interaction prediction, can achieve high generalizability, and may provide new directions and insights for rapid phage screening for therapy.

Numerical simulation and analysis of fatigue performance for the humeral stem.

BACKGROUND AND OBJECTIVE: Fatigue failure of the humeral stem is a severe long-term failure after shoulder arthroplasty, causing harm to patients and resulting in complex revision surgeries. However, there are few studies on humeral stem fatigue testing, and corresponding testing standards have not been established. Therefore, this study aims to investigate the fatigue performance of the humeral stem by establishing an efficient numerical simulation method. METHODS: Material properties are obtained by uniaxial tensile and fatigue tests. A parameterized static analysis program was written, and an automated fatigue numerical simulation platform was established using Abaqus, Fe-safe, and Isight in combination, enabling the establishment of a numerical simulation method for the fatigue performance of the humeral stem. RESULT: Standard testing conditions include an 8 mm diameter humeral stem, a 40-21B humeral head, an 8° tilt angle, and a 2 mm fillet radius. Further research found that the fatigue life of the humeral stem decreases with increasing patient weight, and patients should control their weight after surgery. CONCLUSIONS: The established automated fatigue numerical simulation platform avoids repetitive operations and efficiently completes large-scale calculations, guiding preoperative humeral stem selection and testing.

Thioredoxin-Interacting Protein's Role in NLRP3 Activation and Osteoarthritis Pathogenesis by Pyroptosis Pathway: In Vivo Study.

Thioredoxin-interacting protein (TXNIP) has been involved in oxidative stress and activation of the NOD-like receptor protein-3 (NLRP3) inflammasome, directly linking it to the pyroptosis pathway. Furthermore, pyroptosis may contribute to the inflammatory process in osteoarthritis (OA). The purpose of this study was to investigate the role of TXNIP in activating the NLRP3 inflammasome through the pyroptosis pathway in an OA rat model. Destabilization of the medial meniscus (DMM) was induced in the OA model with intra-articular injections of adeno-associated virus (AAV) overexpressing (OE) or knocking down (KD) TXNIP. A total of 48 healthy rats were randomly divided into six groups (N = 8 each). During the experiment, the rats' weights, mechanical pain thresholds, and thermal pain thresholds were measured weekly. Morphology staining, micro-CT, 3D imaging, and immunofluorescence (IF) staining were used to measure the expression level of TXNIP, and ELISA techniques were employed. OE-TXNIP-AAV in DMM rats aggravated cartilage destruction and subchondral bone loss, whereas KD-TXNIP slowed the progression of OA. The histological results showed that DMM modeling and OE-TXNIP-AAV intra-articular injection caused joint structure destruction, decreased anabolic protein expression, and increased catabolic protein expression and pyroptosis markers. Conversely, KD-TXNIP-AAV slowed joint degeneration. OE-TXNIP-AVV worsened OA by accelerating joint degeneration and damage, while KD-TXNIP-AAV treatment had a protective effect.

A cross-sectional survey on the effects of the COVID-19 pandemic on psychological well-being and quality of life in people with spinal cord injury.

BACKGROUND: SARS-CoV-2 (COVID-19) has disrupted lives worldwide, affecting individuals from all walks of life. Individuals who have a spinal cord injury (SCI) are also affected by this phenomenon. This survey compares the quality of life (QOL), depression, and anxiety of SCI patients before and during COVID-19 in Wuhan City, China. METHODS: A cross-sectional survey utilized an online questionnaire to assess the QOL, levels of anxiety, and depression among 189 SCI patients admitted to Wuhan Tongji Hospital during pandemic from November 2020 to April 2021. Data before COVID-19 outbreak from November to December 2019 was retrieved from hospital records with the same assessment previously performed in-person or during a follow up visit. However, some participants were excluded for various reasons, such as declining to participate, not being admitted to a rehabilitation program due to the pandemic, or being under 18 years old. The World Health Organization's (WHO) QOL-Brief Version (BREF) and disability (DIS) modules, which focus on disability-related QOL, were used to assess the participants' QOL. RESULTS: SCI patients had lower QOL scores during the pandemic compared to pre-pandemic times. Mean scores on the 12-item DIS module significantly differed before and during the COVID-19 period. Participants showed higher adherence to self-isolation and quarantine measures for high-risk encounters (64.94%), but lower compliance with home disinfection and proper rest practices (23.38%). CONCLUSIONS: The COVID-19 pandemic has had a detrimental effect on the QOL of SCI patients in China, highlighting the urgent requirement for telehealth-based rehabilitation to mitigate its impact. It is crucial to provide essential.

The Impact of Preoperative Spinal Injection Timing on the Postoperative Complications of Lumbar Fusion.

OBJECTIVE: To determine the impact of epidural spinal injections (ESIs) on postoperative surgical complications. METHODS: This retrospective all-payer database analysis identified 202,181 adult patients undergoing one- to three-level transforaminal lumbar interbody fusion (TLIF) from 2010 to 2020. A 1:1 exact matching on comorbidities and demographics was performed, creating 2 cohorts: 1) patients who received an ESI within 90 days of surgery and 2) patients who did not receive an ESI. The primary outcome was surgical complication rates between groups at 30 days postoperatively. For the secondary outcome, patients were stratified based on injection time before surgery: 1-30, 31-45, 46-60, 61-75, and 76-90 days. Logistic regression was performed between groups to identify temporal associations of complication rates. The P value was set to 0.05 for the primary analysis, and the Bonferroni correction was utilized for the secondary outcome. RESULTS: Exact matching produced 12,491 pairs for analysis. Groups were well-matched on demographics, comorbidities, and fusion levels. The 30-day postoperative rates of surgical complications, hematomas, wound disruptions, or surgical site infections did not differ between groups (P > 0.05). The rate of cerebrospinal fluid (CSF) leak was increased in the ESI group (0.19% vs. 0.09%, P = 0.042). When temporally stratified, patients receiving an ESI within 30 days had significantly higher odds of CSF leak (odds ratio: 4.24, 95% confidence interval: 1.97-9.14). CONCLUSIONS: Patients who receive an ESI within 30 days of transforaminal lumbar interbody fusion are at an increased risk for CSF leak. While the incidence of CSF leak remains small, it may be advisable to avoid ESIs at least 30 days before surgery for certain patients.

Nitrogen-Mediated Promotion of Cobalt-Based Oxygen Evolution Catalyst for Practical Anion-Exchange Membrane Electrolysis.

Scarce and expensive iridium oxide is still the cornerstone catalyst of polymer-electrolyte membrane electrolyzers for green hydrogen production because of its exceptional stability under industrially relevant oxygen evolution reaction (OER) conditions. Earth-abundant transition metal oxides used for this task, however, show poor long-term stability. We demonstrate here the use of nitrogen-doped cobalt oxide as an effective iridium substitute. The catalyst exhibits a low overpotential of 240 mV at 10 mA cm-2 and negligible activity decay after 1000 h of operation in an alkaline electrolyte. Incorporation of nitrogen dopants not only triggers the OER mechanism switched from the traditional adsorbate evolution route to the lattice oxygen oxidation route but also achieves oxygen nonbonding (ONB) states as electron donors, thereby preventing structural destabilization. In a practical anion-exchange membrane water electrolyzer, this catalyst at anode delivers a current density of 1000 mA cm-2 at 1.78 V and an electrical efficiency of 47.8 kW-hours per kilogram hydrogen.

No Difference in Short-Term Surgical Outcomes from Semaglutide Treatment for Type 2 Diabetes Mellitus after Cervical Decompression and Fusion: A Propensity Score-Matched Analysis.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: To evaluate the impact of semaglutide treatment for Type 2 Diabetes Mellitus (T2DM) on the risk of short-term (<6 months) postoperative complications in patients undergoing primary cervical spine decompression and fusion (CSDF). SUMMARY OF BACKGROUND DATA: Semaglutide, a GLP-1 receptor agonist, is gaining popularity as a weekly injectable medication for the treatment of T2DM and obesity. Existing research indicates that higher levels of HbA1c and obesity are linked to fewer positive results after undergoing spine surgery, particularly cervical decompression and fusion. Nevertheless, there is a scarcity of publications evaluating the influence of semaglutide therapy on surgical complications, including surgical site infection, wound complications, and reoperation within 6 months, which were aggregated into a composite measure. METHODS: The PearlDiver Database was queried from January 2010 to December 2021 for patients with a primary diagnosis of T2DM who underwent CSDF for degenerative pathology. Patients with semaglutide treatment within 6 months before index surgery were propensity score-matched to patients without the treatment, employing age, gender, and Charlson comorbidity index (CCI) as matching covariates. A multivariate regression model was used to investigate the impact of semaglutide treatment on postoperative surgical complications. RESULTS: The propensity score-matched cohort included 596 patients (semaglutide cohort: 298, control cohort: 298). There were no statistically significant differences between cohorts in the composite measure of postoperative surgical complications following index CSDF (OR 1.26, 95% CI 0.83-1.93, P=0.331). Similarly, both 30-day (OR 0.83, 95% CI 0.49-1.42, P=0.589) and 90-day readmission rate (OR 0.89, 95% CI 0.56-1.42, P=0.724) were similar between both cohorts. CONCLUSION: This study suggests that in patients with T2DM, semaglutide treatment is not associated with higher rates of short-term adverse events after CSDF. The effect of semaglutide use on long-term outcomes remains unknown.

Preparation and anti-tumor activity of paclitaxel silk protein nanoparticles encapsulated by biofilm.

In order to overcome the poor bioavailability of paclitaxel (PTX), in this study, self-assembled paclitaxel silk fibronectin nanoparticles (PTX-SF-NPs) were encapsulated with outer membrane vesicles of Escherichia coli (E. coil), and biofilm-encapsulated paclitaxel silk fibronectin nanoparticles (OMV-PTX-SF-NPs) were prepared by high-pressure co-extrusion, the size and zeta potential of the OMV-PTX-SF-NPs were measured. The antitumor effects of OMV-PTX-SF-NPs were evaluated by cellular and pharmacodynamic assays, and pharmacokinetic experiments were performed. The results showed that hydrophobic forces and hydrogen bonding played a major role in the interaction between paclitaxel and filipin proteins, and the size of OMV-PTX-SF-NPs was 199.8 ± 2.8 nm, zeta potential was -17.8 ± 1.3 mv. The cellular and in vivo pharmacokinetic assays demonstrated that the OMV-PTX-SF-NPs possessed a promising antitumor effect. Pharmacokinetic experiments showed that the AUC0-∞ of OMV-PTX-SF-NPs was 5.314 ± 0.77, which was much larger than that of free PTX, which was 0.744 ± 0.14. Overall, we have successfully constructed a stable oral formulation of paclitaxel with a sustained-release effect, which is able to effectively increase the bioavailability of paclitaxel, improve the antitumor activity, and reduce the adverse effects.

miR-27b-3p reduces muscle fibrosis during chronic skeletal muscle injury by targeting TGF-ßR1/Smad pathway.

BACKGROUND: Fibrosis is a significant pathological feature of chronic skeletal muscle injury, profoundly affecting muscle regeneration. Fibro-adipogenic progenitors (FAPs) have the ability to differentiate into myofibroblasts, acting as a primary source of extracellular matrix (ECM). the process by which FAPs differentiate into myofibroblasts during chronic skeletal muscle injury remains inadequately explored. METHOD: mouse model with sciatic nerve denervated was constructed and miRNA expression profiles between the mouse model and uninjured mouse were analyzed. qRT/PCR and immunofluorescence elucidated the effect of miR-27b-3p on fibrosis in vivo and in vitro. Dual-luciferase reporter identified the target gene of miR-27b-3p, and finally knocked down or overexpressed the target gene and phosphorylation inhibition of Smad verified the influence of downstream molecules on the abundance of miR-27b-3p and fibrogenic differentiation of FAPs. RESULT: FAPs derived from a mouse model with sciatic nerves denervated exhibited a progressively worsening fibrotic phenotype over time. Introducing agomiR-27b-3p effectively suppressed fibrosis both in vitro and in vivo. MiR-27b-3p targeted Transforming Growth Factor Beta Receptor 1 (TGF-ßR1) and the abundance of miR-27b-3p was negatively regulated by TGF-ßR1/Smad. CONCLUSION: miR-27b-3p targeting the TGF-ßR1/Smad pathway is a novel mechanism for regulating fibrogenic differentiation of FAPs. Increasing abundance of miR-27b-3p, suppressing expression of TGF-ßR1 and inhibiting phosphorylation of smad3 presented potential strategies for treating fibrosis in chronic skeletal muscle injury.

All-Inside Endoscopic Kidner Procedure for Symptomatic Accessory Navicular.

The accessory navicular (AN) is a common accessory ossicle of the foot. Once patients with ANs become symptomatic, they mostly complain of tenderness over the prominence, which occurs recurrently after a twisting sprain. The Kidner procedure is successful in alleviating symptoms. The excision of the AN is accompanied by rerouting of the posterior tibial tendon to the side of the medial aspect of the navicular. The purpose of this technical note is to report an all-inside endoscopic approach to achieve the Kinder procedure. As an endoscopic approach, the procedure has the advantages of better cosmetic results and less soft-tissue irritation; in addition, the broad ligamentous continuity is protected, the bony prominence is minimized, and sagging of the talonavicular joint is counteracted.

Young TSPC-Derived Exosomal circPVT1 Ameliorates Aging-Impaired Cell Function via SIRT1/NF-κB.

Tendon stem/progenitor cell (TSPC) senescence is often associated with age-dependent tendon diseases and greatly reduces the capacities for tendon repair and replacement. Exosomes contain bioactive molecules and have been increasingly used in regenerative medicine. In the present study, we demonstrated the antiaging effects of young exosomes from circPVT1-overexpressing TSPCs at early passages (circPVT1-exo). These exosomes attenuated the phenotypes of aged TSPCs at late passages (L-TSPCs) by enhancing self-renewal and proliferation abilities, suppressing cell senescence, maintaining their tenogenic capacity, and weakening their osteogenic differentiation. Mechanistically, circPVT1-exo inhibited the NF-κB pathway and increased SIRT1 expression in L-TSPCs. Knockdown of SIRT1 reversed these effects as evidenced by increased senescence, decreased proliferation, and tenogenic differentiation. These results suggest that circPVT1-exo may ameliorate aging-impaired TSPC function by modulating the SIRT1/NF-κB pathway, suggesting that circPVT1-exo has therapeutic potential for age-related diseases.

A modified lateral column lengthening for the treatment of flexible flatfoot: From clinical applications to finite element analysis.

BACKGROUND: Finite element (FE) analysis and clinical follow-up were used to evaluate the efficacy of a modified lateral column lengthening (H-LCL) for treating flexible flatfoot. METHODS: By applying inclusion and exclusion criteria, we selected patients who underwent H-LCL surgery at our institution from January 2019 to January 2023. We compared the Visual Analog Scale (VAS) scores, American Orthopaedic Foot and Ankle Society (AOFAS) scores, Pain Interference (PI), and Physical Function (PF) scores in Patient-Reported Outcomes Measurement Information System (PROMIS) between preoperative and final follow-up assessments of patients, as well as FE submodels. Furthermore, evaluate the H-LCL's biomechanical characteristics and clinical outcome before and after surgery. RESULTS: A total of 66 patients met the criteria. The average surgery time was 69.47 ± 13.22 min, and the follow-up duration was 15.18 ± 6.40 months. In the last follow-up, VAS and PI decreased compared to before surgery, while AOFAS and PF increased compared to before surgery. Meary's angle (dorsoplantar image and lateral image), calcaneal valgus angle, and talonavicular coverage angle decreased compared to before surgery, while the pitch angle increased compared to before surgery. In FE analysis, postoperative tension on the plantar fascia (PF), spring ligament (SL), and posterior tibial tendon (PTT) decreased compared to before surgery, pressure on the talonavicular joint and subtalar joints also decreased compared to before surgery, and there was no significant change in pressure on the calcaneocuboid joint. CONCLUSION: H-LCL in correcting flexible flatfoot resulted in a significant improvement of clinical outcome scores and led to good radiological correction of flatfoot deformities. It can reduce the soft tissue and interosseous pressure in maintaining the foot arch.

Comparison of Clinical Efficacy between Arthroscopic and Open Surgery for Ogden Type 1-2 Peroneal Tendon Dislocation.

OBJECTIVE: While the incidence of peroneal tendon dislocation (PTD) is relatively low, it is frequently underdiagnosed in clinical practice, and the misdiagnosis or improper treatment of this condition may lead to a decline in patients' quality of life. Currently, the surgical treatment options for PTD mainly include open and arthroscopic surgery. However, in order to evaluate the advantages and disadvantages of these two surgical approaches, further comparative research is needed. Therefore, the aim of this study is to investigate the early clinical outcomes of arthroscopic and open surgery in the treatment of Ogden type 1-2 PTD. METHODS: We conducted a comprehensive analysis of 46 patients diagnosed with PTD who underwent surgery at our institution between January 2017 and January 2023. The patients were divided into two groups: the open surgery group, consisting of 26 cases, and the arthroscopic surgery group, consisting of 20 cases. To compare the effectiveness of the surgical approach, we evaluated several parameters, including the integrity of the superior peroneal retinaculum on MRI images, functional scores, pain interference scores, and ankle eversion muscle strength. These assessments are conducted respectively before the surgery, 1 month after the surgery, 3 months after the surgery, and at the final follow-up for each group of patients (at least 6 months post-surgery). Demographics and intergroup comparisons of the two groups of data were analyzed by t-test or the Mann-Whitney U test. Intragroup comparisons of the two groups of data were analyzed by one-way analysis of variance (ANOVA) or the Kruskal-Wallis test, followed by post hoc multiple comparisons. RESULTS: In the intragroup comparisons, both the arthroscopic surgery and the open surgery group demonstrated significant improvement in functional scores, pain interference scores, muscle strength, and MRI findings at the final follow-up postoperatively (p < 0.01). However, the open surgery group exhibited significant improvements in these outcomes at the final follow-up, while the arthroscopic surgery group showed significant improvement at 3 months postoperatively. In intergroup comparisons, the arthroscopic surgery group outperformed the open surgery group in functional scores, pain interference scores, and muscle strength 3 months after the surgery, with statistically significant differences (p < 0.01). CONCLUSION: Arthroscopic surgery offers advantages in early clinical outcomes, such as pain relief, function, and muscle strength improvement. However, over time, both approaches provide similar results regarding effectiveness.

Surgical management of chronic Achilles tendon rupture: evidence-based guidelines.

BACKGROUND: Chronic Achilles tendon ruptures (CATR) often require surgical intervention to restore function. Despite numerous treatment modalities available, the optimal management strategy remains controversial given the limited high-quality evidence available. This article aims to provide evidence-based guidelines for the surgical management of CATR through a comprehensive systematic review of the available data. The consensus reached by synthesizing the findings will assist clinicians in making informed decisions and improving patient outcomes. METHODS: A group of 9 foot surgeons in three continents was consulted to gather their expertise on guidelines regarding the surgical management of CATR. Following the proposal of 9 clinical topics, a thorough and comprehensive search of relevant literature published since 1980 was conducted for each topic using electronic databases, including PubMed, MEDLINE, and Cochrane Library, to identify relevant studies published until 1 October 2023. All authors collaborated in drafting, discussing, and finalizing the recommendations and statements. The recommendations were then categorized into two grades: grade a (strong) and grade b (weak), following the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) concept. Additionally, feedback from 21 external specialists, who were independent from the authors, was taken into account to further refine and finalize the clinical guidelines. RESULTS: Nine statements and guidelines were completed regarding surgical indications, surgical strategies, and postoperative rehabilitation protocol. CONCLUSION: Based on the findings of the systematic review, this guideline provides recommendations for the surgical management of CATR. We are confident that this guideline will serve as a valuable resource for physicians when making decisions regarding the surgical treatment of patients with CATR.

LncRNA AL645608.3 mediates malignant progression of acute myeloid leukemia.

OBJECTIVE: To investigate the role of lncRNA AL645608.3 in the malignant progression of acute myeloid leukemia (AML) cells and explore relevant molecular mechanisms. METHODS: The expression level of AL645608.3 was measured in AML cell lines (THP-1, HL-60, KG-1, and AML-193) via real-time quantitative polymerase chain reaction (RT-qPCR). Small hairpin RNA (shRNA) and open reading frame of AL645608.3 were cloned into lentiviral vectors and were infected into THP-1 and AML-193 cells. The expression of casitas B-lineage lymphoma (CBL), interferon regulatory factor 6 (IRF6), and interferon beta 1 (IFNB1) was detected through RT-qPCR, and western blot. Co-immunoprecipitation (Co-IP) on IRF6 was conducted. Matrix metalloprotease-9 (MMP-9) activity was evaluated via gelatin zymography assay. RESULTS: LncRNA AL645608.3 was expressed in the four AML cell lines (THP-1, HL-60, KG-1, and AML-193). Silencing AL645608.3 mitigated the expression of IRF6 and IFNB1 but elevated the expression of CBL in THP-1 cells. Oppositely, AL645608.3 overexpression up-regulated the expression of IRF6 and IFNB1 but decreased the expression of CBL in AML-193 cells. Co-IP results proved that AL645608.3 could directly mediate IRF6 activity in THP-1 and AML-193 cells. MMP-9 activity was decreased by AL645608.3 knockdown and was improved by AL645608.3 overexpression in AML-193 cells. CONCLUSION: AL645608.3 is expressed in different AML cell lines, and mediates the expression of CBL, IRF6, IFNB1, and MMP-9. These findings might deepen our comprehension of the molecular mechanisms underlying AML.

Synthetic Interbody Devices and Traditional Bone Graft Are Associated With a Similar Rate of Surgical Complications After 1-2 Level Anterior Cervical Discectomy and Fusions.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: To compare the rates of all-cause surgical complications of synthetic interbody devices versus allograft or autograft in patients undergoing 1-2 levels anterior cervical discectomy and fusion (ACDF) procedures. SUMMARY OF BACKGROUND DATA: Cervical degenerative disorders affect up to 60% of older adults in the United States. Both traditional allograft or autograft and synthetic interbody devices (polyetheretherketone or titanium) are used for decompression and arthrodesis, with increasing utilization of the latter. However, the differences in their postsurgical complication profiles are not well-characterized. PATIENTS AND METHODS: Patients who underwent 1-2 level ACDFs for cervical radiculopathy or myelopathy between 2010 and 2022 were identified using the PearlDiver Mariner all-claims insurance database. Patients undergoing surgery for nondegenerative pathologies, such as tumors, trauma, or infection, were excluded. 1:1 exact matching was performed based on factors that were significant predictors of all-cause surgical complications in a linear regression model. The primary outcome measure was the development of all-cause surgical complications after 1-2 level ACDFs. The secondary outcome was all-cause medical complications. RESULTS: 1:1 exact matching resulted in two equal groups of 11,430 patients who received treatment with synthetic interbody devices or allograft/autograft. No statistically significant difference in all-cause surgical complications was found between the synthetic cohort and the allograft or autograft cohort after 1-2 level ACDFs (Relative Risk: 0.86, 95% confidence interval: 0.730-1.014, P = 0.079). No significant differences were observed regarding any specific surgical complications except for pseudoarthrosis (Relative Risk: 0.73, 95% confidence interval: 0.554-0.974, P = 0.037), which was higher in the allograft/autograft cohort. CONCLUSION: After 1:1 exact matching to control for confounding variables, the findings of this study suggest that all-cause surgical complications are similar in patients undergoing ACDFs with synthetic interbody devices or allograft/autographs. However, the rate of pseudarthrosis appears to be higher in patients with allograft/autographs. Future prospective studies are needed to corroborate these findings.

HPF1 regulates tendon stem/progenitor cell senescence and tendon repair via PARP1-mediated poly-ADP ribosylation of HuR.

BACKGROUND: Tendon stem/progenitor cells (TSPCs) play a vital role in tendon repair, regeneration and homeostasis. However, the specific mechanism of TSPCs aging is still unclear. OBJECTIVE: This study aims to explore the role and molecular mechanism of HPF1 in the aging of TSPCs. METHODS: Young and aged TSPCs (Y-TSPCs and A-TSPCs) were acquired from 3 to 4 and 24-26-month-old Sprague-Dawley male rats, TSPCs (Y-TSPCs and A-TSPCs) were subjected to senescence-associated ß-galactosidase (SA-ß-Gal))staining and telomerase activity detection, p16, p21, Scx, Tnmd, Col1, Col3HPF1 and PAPR1 expression levels were detected by Western blot or Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR), Reciprocal co-immunoprecipitation (co-IP) was used to explore the interaction between HPF1 and PARP1. Ribonucleoprotein immunoprecipitation (RNP-IP) was used to analyze the binding of HuR to the senescence marker gene mRNAs, IP was used to perform HPF1 to the PARylation of HuR, and the half-life of p16 and p21 were detected. Finally, we established an in vivo model, and the tendon tissue was used to perform hematoxylin and eosin (HE) and masson's trichrome staining, as well as the immunohistochemical analysis of Col I and TNMD. RESULTS: Compared with Y-TSPCs, A-TSPCs had significantly enhanced cell senescence and significantly reduced tendon differentiation ability, and significantly increased the expression of HPF1 and PARP1. In addition, HPF1 and PARP1 interacted and coordinated the senescence and differentiation of TSPCs, HPF1 could also regulate the expression of p21 and p21, the interaction of p16 or p21 with HuR, and the poly-ADP ribosylation of PARP1 to HuR. HPF1 overexpression and siHuR co-transfection significantly reduced the half-life of p16 and p21, and HPF1 and PARP1 regulated the mRNA levels of p16 and p21 through HuR. Finally, in vivo experiments have shown that HPF1 or PARP1 overexpression could both inhibit the ability of tendon differentiation and promote cell senescence. CONCLUSIONS: HPF1 promoted the senescence of TSPCs and inhibits the tendon differentiation of TSPCs through PARP1-mediated poly-ADP ribosylation of HuR.