The modified suture-bridge technique for treating avulsion fracture of minors tibial eminence of anterior cruciate ligament: a retrospective study.

PURPOSE: This study aimed to evaluate the clinical and radiological outcomes of modified suture-bridge technique fixation for anterior cruciate ligament (ACL) tibial avulsion fracture. METHOD: Minors who underwent arthroscopic reduction and modified suture bridge fixation of ACL tibial avulsion fracture between January 2018 and January 2022 were retrospectively analyzed. Postoperative MRI and X-ray examinations were performed to evaluate the presence of epiphyseal plate injury and fracture healing. Moreover, KT-1000 side-to-side difference, Lachman test, range of motion (ROM), the subjective Knee score of the International Knee Documentation Committee (IKDC), Lysholm Knee score, and Tegner activity grade score were evaluated preoperatively and at the minimum 1-year follow-up visit. RESULTS: A total of 16 participants met the inclusion criteria. They had a mean age of 12.6 years (range, 9-16 years); mean time to surgery, 6.9 days (range, 2-13 days) and had a minimum of 12 months clinical follow-up (mean, 25.4 months; range, 12-36 months) after surgery. Postoperative radiographs and MRI showed no injury to the epiphyseal plate, optimal reduction immediately after the operation, and bone union within three months in all patients. All of the following showed significant improvements (pre- vs. postoperatively): mean KT-1000 side-to-side difference (8.6 vs. 1.5; p < 0.05), Lachman tests (2 grade 9 and 3 grade 7 vs. 0 grade 12 and 1 grade 4; p < 0.05), IKDC subjective score (48.3 vs. 95.0; p < 0.05), mean Lysholm score (53.9 vs. 92.2; p < 0.05), mean Tegner activity score (3.2 vs. 8.3; p < 0.05) and mean ROM (42.9°vs 133.1°; p < 0.05). CONCLUSION: Arthroscopic reduction and modified suture bridge fixation for ACL tibial avulsion fracture is a dependable and recommended treatment that can effectively restore the stability and function of the knee and is worthy of clinical promotion.

Pongamol Alleviates Neuroinflammation and Promotes Autophagy in Alzheimer's Disease by Regulating the Akt/mTOR Signaling Pathway.

Alzheimer's disease (AD), one of the neurodegenerative disorders, is highly correlated with the abnormal hyperphosphorylation of Tau and aggregation of ß-amyloid (Aß). Oxidative stress, neuroinflammation, and abnormal autophagy are key drivers of AD and how they contribute to neuropathology remains largely unknown. The flavonoid compound pongamol is reported to possess a variety of pharmacological activities, such as antioxidant, antibacterial, and anti-inflammatory. This study investigated the neuroprotective effect and its mechanisms of pongamol in lipopolysaccharide (LPS)-induced BV2 cells, d-galactose/sodium nitrite/aluminum chloride (d-gal/NaNO2/AlCl3)-induced AD mice, and Caenorhabditis elegans models. Our research revealed that pongamol reduced the release of inflammatory factors IL-1ß, TNF-α, COX-2, and iNOS in LPS-induced BV2 cells. Pongamol also protected neurons and significantly restored memory function, inhibited Tau phosphorylation, downregulated Aß aggregation, and increased oxidoreductase activity in the hippocampus of AD mice. In addition, pongamol reversed the nuclear transfer of NF-κB and increased the levels of Beclin 1 and LC3 II/LC3 I. Most importantly, the anti-inflammatory and promoter autophagy effects of pongamol may be related to the regulation of the Akt/mTOR signaling pathway. In summary, these results showed that pongamol has a potential neuroprotective effect, which greatly enriched the research on the pharmacological activity of pongamol for improving AD.

High Dynamic Range Probing of Single-Molecule Mechanical Force Transitions at Cell-Matrix Adhesion Bonds by a Plasmonic Tension Nanosensor.

Mechanical signals in animal tissues are complex and rapidly changed, and how the force transduction emerges from the single-cell adhesion bonds remains unclear. DNA-based molecular tension sensors (MTS), albeit successful in cellular force probing, were restricted by their detection range and temporal resolution. Here, we introduced a plasmonic tension nanosensor (PTNS) to make straight progress toward these shortcomings. Contrary to the fluorescence-based MTS that only has specific force response thresholds, PTNS enabled the continuous and reversible force measurement from 1.1 to 48 pN with millisecond temporal resolution. We used the PTNS to visualize the high dynamic range single-molecule force transitions at cell-matrix adhesions during adhesion formation and migration. Time-resolved force traces revealed that the lifetime and duration of stepwise force transitions of molecular clutches are strongly modulated by the traction force through filamentous actin. The force probing technique is sensitive, fast, and robust and constitutes a potential tool for single-molecule and single-cell biophysics.

Pongamol Prevents Neurotoxicity via the Activation of MAPKs/Nrf2 Signaling Pathway in H2O2-Induced Neuronal PC12 Cells and Prolongs the Lifespan of Caenorhabditis elegans.

Despite tremendous advances in modern medicine, effective prevention or therapeutic strategies for age-related neurodegenerative diseases such as Alzheimer's disease (AD) remain limited. Growing evidence now suggests that oxidative stress and apoptosis are increasingly associated with AD as promising therapeutic targets. Pongamol, a flavonoid, is the main constituent of pongamia pinnata and possesses a variety of pharmacological activities such as antioxidant, anti-aging and anti-inflammatory. In the present study, we investigated the antioxidant effects and mechanisms of pongamol in H2O2-induced PC12 cells and Caenorhabditis elegans (C. elegans). Our findings revealed that pongamol reduced cellular damage and apoptosis in H2O2-induced PC12 cells. Furthermore, pongamol reduced levels of apoptosis-related proteins Bax, Cyto C, Cleaved Caspase-3, and Cleaved PARP1, and increased the level of anti-apoptotic protein Bcl-2. Pongamol also effectively attenuated the level of oxidative stress markers such as glutathione (GSH) and reactive oxygen species (ROS) in H2O2-induced PC12 cells. Additionally, pongamol possessed antioxidant activity in H2O2-induced PC12 cells through the MAPKs/Nrf2 signaling pathway. Furthermore, pongamol exerted neuroprotective and anti-aging effects in C. elegans. All together, these results suggested that pongamol has a potential neuroprotective effect through the modulation of MAPKs/Nrf2 signaling pathway.

Locally delivered hydrogels with controlled release of nanoscale exosomes promote cardiac repair after myocardial infarction.

Compared with stem cells, exosomes as a kind of nanoscale carriers intrinsically loaded with diverse bioactive molecules, which had the advantages of high safety, small size, and ethical considerations in the treatment of myocardial infarction, but there are still problems such as impaired stability and rapid dissipation. Here, we introduce a bioengineered injectable hyaluronic acid hydrogel designed to optimize local delivery efficiency of trophoblast stem cells derived-exosomes. Its hyaluronan components adeptly emulates the composition and modulus of pericardial fluid, meanwhile preserving the bioactivity of nanoscale exosomes. Additionally, a meticulously designed hyperbranched polymeric cross-linker facilitates a gentle cross-linking process among hyaluronic acid molecules, with disulfide bonds in its molecular framework enhancing biodegradability and conferring a unique controlled release capability. This innovative hydrogel offers the added advantage of minimal invasiveness during administration into the pericardial space, greatly extending the retention of exosomes within the myocardial region. In vivo, this hydrogel has consistently demonstrated its efficacy in promoting cardiac recovery, inducing anti-fibrotic, anti-inflammatory, angiogenic, and anti-remodeling effects, ultimately leading to a substantial improvement in cardiac function. Furthermore, the implementation of single-cell RNA sequencing has elucidated that the pivotal mechanism underlying enhanced cardiac function primarily results from the promoted clearance of apoptotic cells by myocardial fibroblasts.

A study of protective effects of Mus81 in preeclampsia.

This study was to investigate the effect and mechanism of Mus81 in severe PE. 20 cases of pregnant women with severe PE and 20 cases of healthy pregnant women were enrolled. Placental tissues were collected after delivery, and the expression of Mus81 in placental tissues was detected by qRT-PCR and Western blot (WB). The si-Mus81 adenovirus was used to construct a pregnant mouse model of Mus81 down-expression in vivo, to clarify the effect of Mus81 on pregnant mice and blood pressure, urinary protein, serum sFLT1 and fetal weight in PE. After overexpression of Mus81 in HTRB-S/Vneo cells, the proliferation, migration and apoptosis of the cells were measured by EdU staining, flowcytometry, qRT-PCR and cell scratch test. Protein expression of the Wnt/ß-catenin signaling pathway was detected by WB. To further explore the mechanism, Wnt/ß-catenin inhibitor DKK1 inhibitor was added to HTRB-S/Vneo cells and then Ad-Mus81 was added for co-incubation for 48 h. Protein expressions p-ß-catenin and activated-ß-catenin were detected by WB. Bax and Bcl-2 were detected by qRT-PCR, and the proliferation of HTRB-S/Vneo cells was measured by EdU staining. Cell migration was detected by scratch test. The expression of Mus81 in the placental tissues of pregnant women with severe PE was lower than that in normal placental tissues. The blood pressure, urine protein and serum sFLT1 protein levels of Mus81 knockdown mice were all upregulated and the fetal weight was decreased after the injection of si-Mus81, which successfully simulated the characteristics of PE. After overexpression of Mus81, the proliferation and migration of HTRB-S/Vneo cells were enhanced, while the apoptosis was decreased. After overexpression of Mus81, the expression levels of p-ß-catenin decreased while active-ß-catenin increased obviously. Then, DKK1 inhibitor and Ad-Mus81 were added to the HTRB-S/Vneo cells and co-incubated for 48 h. Compared with the Ad-Mus81+DMSO group, the expression of p-ß-catenin increased while activated-ß-catenin decreased in the Ad-Mus81+DKK1 inhibitor group. The proliferation and migration decreased, but apoptosis of HTRB-S/Vneo cells was increased. Mus81 can regulate the proliferation, migration and apoptosis of trophoblast cells through the Wnt/ß-catenin pathway, which plays an important role in maintaining the normal physiological function of trophoblast cells and is also involved in the occurrence and development of severe PE.

Cathepsin D Attenuates the Proliferation of Vascular Smooth Muscle Cells Induced by the AGE/RAGE Pathway by Suppressing the ERK Signal.

BACKGROUND: In this study, we aimed to clarify the role and mechanism by which Cathepsin D (CTSD) mediates the advanced glycation end products (AGEs)-induced proliferation of vascular smooth muscle cells (VSMCs). METHODS: We conducted a Western blotting assay and co-immunoprecipitation assay to detect the expression of target proteins and the interaction between different proteins. Cell Counting Kit-8 (CCK-8) assay and 5- ethynyl-2'-deoxyuridine (EdU) were used to evaluate the proliferation. RESULTS: AGEs significantly promoted phenotypic switching and proliferation of VSMCs in a concentration-dependent manner. This effect of AGEs was accompanied by inhibition of CTSD. Both the proliferation of VSMCs and inhibition of CTSD induced by AGEs could be attenuated by the specific inhibitor of the receptor for advanced glycation end products (RAGE), FPS-ZM1. Overexpression of CTSD significantly alleviated these effects of AGEs on VSMCs. The mechanism of CTSD action in VSMCs was also explored. Overexpression of CTSD reduced the activation of p-ERK caused by AGEs. By contrast, the knockdown of CTSD, elicited using a plasmid containing short hairpin RNA (shRNA) against CTSD, further increased the activation of p-ERK compared to AGEs alone. Additionally, co-immunoprecipitation studies revealed an endogenous interaction between CTSD, a protease, and p-ERK, its potential substrate. CONCLUSION: It has been demonstrated that CTSD downregulates the level of phosphorylated ERK by degrading its target, and this interaction plays a critical role in the proliferation of VSMCs induced by the AGE/RAGE axis. These results provide a novel insight into the prevention and treatment of vascular complications in diabetes.

Revealing the Corrosion Resistance of 316 L Stainless Steel by an In Situ Grown Nano Oxide Film.

It is widely accepted that the corrosion resistance of stainless steel originates from a compact Cr2O3 layer in the native passive film that serves as a barrier to aggressive ions. However, this suggestion has been questioned by some researchers. They believe that protectiveness might be related to the film recovery. Herein, the pitting development of bare 316 L stainless steel was compared with a corrosion-resistance enhanced steel obtained by tuning the native passive film of the alloy. Statistical software was employed for tracing the size and number of pits on the alloy surface. The statistical results for 12 weeks in 1 M sodium chloride solution (80 °C) revealed that there was a crossover in the growing rates of stable pits (diameter > 9 µm) between the bare alloy and the film-enhanced one. Stable pits on bare 316 L occurred early but showed a comparatively slow increase in the following weeks, demonstrating that self-repairability of metastable pits rather than impermeability of the native passive film plays the key role in the early stage of pitting corrosion.

A Super Anticorrosive Ultrathin Film by Restarting the Native Passive Film on 316L Stainless Steel.

The corrosion resistance of stainless steel is attributed to the extraordinary protectiveness of the ultrathin native passive film (~3 nanometers) on alloy surface. This protectiveness, independent of alloying, can possibly be further increased by modifying the native film to resist corrosion in harsh conditions. However, the modification based on the film itself is extremely difficult due to its rapid, self-limiting growth. Here we present a strategy by using low-temperature plasma processing so as to follow the growth kinetics of the native film. The native oxide film is restarted and can uniformly grow up to ~15 nanometers in a self-limiting manner. High-resolution TEM found that the film exhibited a well-defined, chemical-ordering layered structure. The following corrosion tests revealed that the anodic current density of the alloy decreased by two orders of magnitude in 0.6 M NaCl solution with a remarkable increase of pitting potential. This enhancement is also observed in Fe-Cr alloys with Cr contents above ~10.5 wt.%. The superior protectiveness of the alloy is thus attributed to the continuous and thickened high-quality ultrathin Cr2O3 layer in the restarted film.

MiR-139-3p Targets CHEK1 Modulating DNA Repair and Cell Viability in Lung Squamous Carcinoma Cells.

Non-small-cell lung carcinoma (NSCLC) can be classified into several subtypes, where lung squamous carcinoma (LUSC) is one common subtype. Though miR-139-3p has been reported to be implicated in the development of various cancers, its mechanisms and functions remain unclear in LUSC. In this study, miR-139-3p was screened as one of the significantly down-regulated miRNAs in LUSC by an "edgeR" differential analysis based on TCGA database, which was verified by qRT-PCR in LUSC cell lines as well. The viability and cell cycle of the LUSC cells were examined by CCK-8 and flow cytometry, respectively, exhibiting that upregulating miR-139-3p restrained cell viability and thus accelerating the cell cycle. To explain this phenomenon, we further explored the downstream target gene through miRTarBase and starBase databases, where CHEK1 was predicted as one candidate. The targeting relationship was verified by a dual luciferase assay, identifying that CHEK1 could be targeted by miR-139-3p. Then, qRT-PCR and western blot analyses were performed to detect the expression of CHEK1 mRNA and proteins under the alteration of miR-139-3p expression. Rescue experiments were conducted to confirm the impacts of miR-139-3p/CHEK1 axis on the cell viability and cell cycle of LUSC. The results indicated that the effects of miR-139-3p on the LUSC cell phenotypes could be blocked by overexpressing CHEK1. In conclusion, our study provides a novel insight into the regulatory role of miR-139-3p in the development of LUSC.

A fluorogenic RNA aptamer nanodevice for the low background imaging of mRNA in living cells.

A fluorogenic RNA aptamer nanodevice integrating an entropy-driven RNA amplifier with near-infrared (NIR) light control was developed, affording high contrast and sensitivity for imaging low-abundance mRNA in living cells. The design principle offers a new approach for developing low-background imaging systems for live-cell studies and manipulation.

EMI Shielding Nanocomposite Laminates with High Temperature Resistance, Hydrophobicity and Anticorrosion Properties.

High-performance multifunctional EMI shielding composite fabricated by low-cost method is increasingly required. Herein, novel EMI shielding nanocomposite laminates, consisting of composite prepreg of carbon fiber/epoxy resin/carbon nanotube film, were manufactured by facile electric heating of carbon nanotube film. The results indicated that composite with excellent specific shielding effectiveness of 0.07 dB/µm, 47 dB cm3/g and metamaterial properties can be designed by composite prepreg, and the primary shielding mechanism of it was reflection loss, along with interface polarization loss and conductive loss, which was superior to lots of shielding materials including carbon nanotube-based, carbon black-based, carbon nanofiber-based and graphene-based materials reported previously. Meanwhile, highly required excellent properties, including the thermostability with initial decomposition temperature up to 300 °C, hydrophobicity over contact angle of 115°, corrosion resistance of the composite with metal-free modification, and function as structural laminate compared with previous studies were demonstrated, which suggested tremendous potentials of the multifunctional EMI shielding composites in harsh environment.

DNA Origami Frameworks Enabled Self-Protective siRNA Delivery for Dual Enhancement of Chemo-Photothermal Combination Therapy.

Although chemotherapy and photothermal therapy are widely used to combat cancer, their efficacy is often limited by multidrug resistance. Small interfering RNAs (siRNAs) have ability to suppress the expression of target genes, which has been extensively employed for combating the multidrug resistance to chemodrugs and hyperthermia in cancer therapy. However, efficient delivery of siRNAs along with chemo-photothermal agents in vivo is still an enormous challenge. Herein, octahedral DNA origami frameworks (OctDOFs) are constructed as a nanovehicle for precise organization and orchestrated delivery of siRNAs, chemodrugs (doxorubicin, Dox), and photothermal agents (gold nanorods, AuNRs) in combinatorial treatment of cancer. The inner cavity of the rigid OctDOFs structure is able to shield the encapsulated siRNAs during transportation by sterically hindering RNase degradation and protein binding, thus achieving effective downregulation of connective tissue growth factor (CTGF) and heat shock protein 72 (HSP72) for dual sensitization of cancer cells to chemodrugs and hyperthermia. By amplifying chemo-photothermal therapeutic potency with siRNAs, the proposed OctDOFs exhibited superior cytotoxicity and tumor inhibition efficacy in vitro and in vivo. This nanovehicle creates a promising siRNA delivery platform for precise medication and combination therapy.

Deacetylation-dependent regulation of PARP1 by SIRT2 dictates ubiquitination of PARP1 in oxidative stress-induced vascular injury.

Poly(ADP-ribose) polymerase 1 (PARP1) has a major regulatory role in cardiovascular disease. However, inhibiting PARP1 activity does not significantly improve clinical outcomes of cardiovascular disease, which suggests that the regulatory mechanism of PARP1 in cardiovascular disease is unclear. Here, we focused on deacetylation regulatory mechanisms of PARP1 and crosstalk of PARP1 post-translational modifications. We uncovered the crucial molecular interactions and protein modifications of deacetylase Sirtuin 2 (SIRT2) and PARP1 in vascular damage. The results showed that SIRT2 was involved in this process and oxidative stress damage factor PARP1 was a novel physiological substrate of SIRT2. SIRT2 interacted with PARP1 at the PARP-A-helical domain and deacetylated the K249 residue of PARP1. Furthermore, SIRT2 promoted ubiquitination of the K249 residue of PARP1 via mobilization of the E3 ubiquitin ligase WW domain-containing protein 2 (WWP2), which led to proteasome-mediated degradation of PARP1. Knockout of SIRT2 in mice and cells increased PARP1 acetylation and decreased PARP1 ubiquitination, which in turn aggravated oxidative stress-induced vascular injury and remodeling. Conversely, overexpression of SIRT2 in mice and cells decreased PARP1 acetylation, increased PARP1 ubiquitination, and relieved oxidative stress-induced vascular injury and remodeling. Overall, this study revealed a previously unrecognized mechanistic link between SIRT2 and PARP1 in the regulation of oxidative stress-induced vascular injury.

Comprehensive Bioinformatics Analysis Identifies POLR2I as a Key Gene in the Pathogenesis of Hypertensive Nephropathy.

Hypertensive nephropathy (HN), mainly caused by chronic hypertension, is one of the major causes of end-stage renal disease. However, the pathogenesis of HN remains unclarified, and there is an urgent need for improved treatments. Gene expression profiles for HN and normal tissue were obtained from the Gene Expression Omnibus database. A total of 229 differentially co-expressed genes were identified by weighted gene co-expression network analysis and differential gene expression analysis. These genes were used to construct protein-protein interaction networks to search for hub genes. Following validation in an independent external dataset and in a clinical database, POLR2I, one of the hub genes, was identified as a key gene related to the pathogenesis of HN. The expression level of POLR2I is upregulated in HN, and the up-regulation of POLR2I is positively correlated with renal function in HN. Finally, we verified the protein levels of POLR2I in vivo to confirm the accuracy of our analysis. In conclusion, our study identified POLR2I as a key gene related to the pathogenesis of HN, providing new insights into the molecular mechanisms underlying HN.

Septin4 promotes cardiomyocytes apoptosis by enhancing the VHL-mediated degradation of HIF-1α.

Septin4, a protein localized at mitochondrion, can promote cells apoptosis mainly by binding XIAP (X-linked inhibitors of apoptosis), however, nothing is known about the role and mechanism of Septin4 in cardiomyocytes apoptosis. Here in the current study, we report that HIF-1α (hypoxia-inducible factor 1 alpha) is a novel interacting protein with Septin4 at Septin4-GTPase domain. In addition, Septin4 enhances the binding between HIF-1α and the E3 ubiquitin ligase VHL (von Hippel-Lindau protein) to down-regulate HIF-1α, and by reducing cardio-protective factor HIF-1α levels, Septin4 aggravated the hypoxia-induced cardiomyocytes apoptosis. We believe these findings will be beneficial to provide effective strategies for clinical treatment of myocardial ischemia and the subsequent injury caused by myocardial hypoxia.

The role of SIRT2 in vascular-related and heart-related diseases: A review.

At present, cardiovascular disease is one of the important factors of human death, and there are many kinds of proteins involved. Sirtuins family proteins are involved in various physiological and pathological activities of the human body. Among them, there are more and more studies on the relationship between sirtuin2 (SIRT2) protein and cardiovascular diseases. SIRT2 can effectively inhibit pathological cardiac hypertrophy. The effect of SIRT2 on ischaemia-reperfusion injury has different effects under different conditions. SIRT2 can reduce the level of reactive oxygen species (ROS), which may help to reduce the severity of diabetic cardiomyopathy. SIRT2 can affect a variety of cardiovascular diseases, energy metabolism and the ageing of cardiomyocytes, thereby affecting heart failure. SIRT2 also plays an important role in vascular disease. For endothelial cell damage used by oxidative stress, the role of SIRT2 is bidirectional, which is related to the degree of oxidative stress stimulation. When the degree of stimulation is small, SIRT2 plays a protective role, and when the degree of stimulation increases to a certain level, SIRT2 plays a negative role. In addition, SIRT2 is also involved in the remodelling of blood vessels and the repair of skin damage.

Catalytic route electrochemiluminescence microscopy of cell membranes with nitrogen-doped carbon dots as nano-coreactants.

Catalytic route electrochemiluminescence (ECL) microscopy enables imaging upper cell membranes with freely diffusing Ru(bpy)32+ as the emitter and nitrogen-doped carbon dots as the nano-coreactants and labels. This strategy provides a vertical resolution when studying the ECL profiles at different heights and realizes the ECL imaging of the externalized phosphatidylserine.

Highly Biocompatible Plasmonically Encoded Raman Scattering Nanoparticles Aid Ultrabright and Accurate Bioimaging.

Plasmonically engineered nanomaterials based on Au-Ag for surface-enhanced Raman scattering (SERS)-based biomedicine is of great importance but is still far behind clinical needs because of the poor compatibility between sensitivity and safety. Here, robust plasmonically encoded Raman scattering nanoparticles, named Au core-Raman-active molecule-Ag shell-Au shell nanoparticles (CMSS NPs), were synthesized. The as-developed CMSS NPs possess a unique exterior ultrathin Au shell (∼2.2 nm thickness) that plays double key roles as an effective wrapping layer as well as a plasmonic enhancing layer, thereby showing not only extraordinary stability against oxidative damages and bioerosion but also outstanding SERS sensitivity because of the stronger in-built electromagnetic field, achieving a significant SERS enhancement factor of 3.3 × 108. The results confirm that the individual CMSS NPs show ultrahigh brightness, reproducibility, selectivity, and biocompatibility in single-cell Raman imaging. Moreover, ultrabright in vivo tumor imaging with 1 × 1 mm2 area can be quickly achieved within 35 s under open-air condition. Furthermore, by secondary plasmonic encoding, the CMSS NPs flexibly serve as nanobeacon to monitor single-cell autophagy with improved accuracy. The CMSS NPs are expected as versatile SERS probes that enable ultrabright, fast, and precise Raman-based bioimaging and clinical bioapplications.