Structural characteristics of sulfated xylogalactomannan isolated from Caulerpa okamurae and its anticoagulant activity.

Due to wonderful taste, rich nutrition and biological functions, many marine green algae in the genus Caulerpa have been recently developed as candidates for green caviar. A novel water-soluble sulfated xylogalactomannan CO-0-1 was obtained from the green algae Caulerpa okamurae. CO-0-1 was mainly composed of mannose (Man), galactose (Gal), and xylose (Xyl) at the ratio of 4.4:4.0:1.4 with the molecular weight at 470 kDa and the sulfate content at 12.78 %. The sulfated xylogalactomannan had Man at the backbone with →4)-ß-D-Manp-(1→ and →2)-ß-D-Manp-(1→ as the main chain and branches at O-3 position. The side chains contained →3)-ß-D-Galp-(1→ and minor →2)-ß-D-Xylp(1→. The sulfate groups only distributed at the side chains and at O-6 position of →3)-ß-D-Galp-(1→ and O-4 position of (1→2)-ß-D-Xylp. The anticoagulant activity indicated that CO-0-1 displayed intrinsic anticoagulant and specific anti-thrombin activities. The investigation expanded the utilization and development scene and scope of the green algae Caulerpa okamurae.

Epigallocatechin gallate attenuated high glucose-induced pancreatic beta cell dysfunction by modulating DRP1-mediated mitochondrial apoptosis pathways.

Long-term exposure to hyperglycemic conditions leads to ß-cell dysfunction, particularly mitochondrial dysfunction, and inflammatory and oxidative stress responses, which are considered the primary causes of ß-cell death and the hallmarks of diabetes. Plant-active ingredients may play a key role in glycemic control. Epigallocatechin gallate (EGCG) is a characteristic catechin derived from tea that possesses anti-diabetic properties. Nonetheless, its underlying mechanisms remain elusive. Herein, the protective role of EGCG on high glucose (33 mM)-induced pancreatic beta cell dysfunction and its possible molecular mechanisms were investigated. Briefly, MIN6 cells were treated with glucose and EGCG (10 µM, 20 µM, and 40 µM) for 48 h. Our results revealed that EGCG dose-dependently restored mitochondrial membrane potential and concomitantly alleviated cell apoptosis. Mechanistically, the expression level of apoptotic protein BAX and Dynamic related protein 1 (DRP1) was significantly downregulated following EGCG treatment, whereas that of the anti-apoptotic protein BCL-2 was significantly upregulated. Taken together, EGCG alleviated high glucose-induced pancreatic beta cell dysfunction by targeting the DRP1-related mitochondrial apoptosis pathway and thus can serve as a nutritional intervention for the preservation of beta cell dysfunction in patients with type 2 diabetes mellitus.

Mussel-inspired antimicrobial hydrogel with cellulose nanocrystals/tannic acid modified silver nanoparticles for enhanced calvarial bone regeneration.

Bacterial infection is a serious challenge in the treatment of open bone defects, and reliance on antibiotic therapy may contribute to the emergence of drug-resistant bacteria. To solve this problem, this study developed a mineralized hydrogel (PVA-Ag-PHA) with excellent antibacterial properties and osteogenic capabilities. Silver nanoparticles (CNC/TA@AgNPs) were greenly synthesized using natural macromolecular cellulose nanocrystals (CNC) and plant polyphenolic tannins (TA) as stabilizers and reducing agents respectively, and then introduced into polyvinyl alcohol (PVA) and polydopamine-modified hydroxyapatite (PDA@HAP) hydrogel. The experimental results indicate that the PVA-Ag-PHA hydrogel, benefiting from the excellent antibacterial properties of CNC/TA@AgNPs, can not only eliminate Staphylococcus aureus and Escherichia coli, but also maintain a sustained sterile environment. At the same time, the HAP modified by PDA is uniformly dispersed within the hydrogel, thus releasing and maintaining stable concentrations of Ca2+ and PO43- ions in the local environment. The porous structure of the hydrogel with excellent biocompatibility creates a suitable bioactive environment that facilitates cell adhesion and bone regeneration. The experimental results in the rat critical-sized calvarial defect model indicate that the PVA-Ag-PHA hydrogel can effectively accelerate the bone healing process. Thus, this mussel-inspired hydrogel with antibacterial properties provides a feasible solution for the repair of open bone defects, demonstrating the considerable potential for diverse applications in bone repair.

Azimuthal polarized quasi-bound states in the continuum based on rotational symmetry breaking.

Bound states in the continuum (BICs) allow to obtain an ultrahigh-quality-factor optical cavity. Nevertheless, BICs must be extended in one or more directions, substantially increasing the device footprint. Although super-cavity mode quasi-BICs supported by single nanopillars have been demonstrated recently, their low-quality factor and localized electromagnetic field inside the dielectric nanopillar are insufficient for high-sensitivity refractive index sensing applications. We propose a ring structure rotated by a dielectric sectorial nanostructure, which can achieve a high quality factor by breaking the rotational symmetry of the ring structure with a footprint as small as 3 µm2. As a straightforward application, we demonstrate high performance local refractive index and nanoscale film thickness sensing based on rotational symmetry breaking induced BICs. These BICs reach quality factor and sensitivity of one order of magnitude better than those of conventional super-cavity mode BICs. The proposed method provides insights into the design of compact high quality factor photonic devices, opening up new possibilities for applications in refractive index and nanoscale film thickness sensing.

Defect-Engineered Tin Disulfide Nanocarriers as "Precision-Guided Projectile" for Intensive Synergistic Therapy.

Nanoformulations with endogenous/exogenous stimulus-responsive characteristics show great potential in tumor cell elimination with minimal adverse effects and high precision. Herein, an intelligent nanotheranostic platform (denoted as TPZ@Cu-SnS2-x /PLL) for tumor microenvironment (TME) and near-infrared light (NIR) activated tumor-specific therapy is constructed. Copper (Cu) doping and the resulting sulfur vacancies can not only improve the response range of visible light but also improve the separation efficiency of photogenerated carriers and increase the carrier density, resulting in the ideal photothermal and photodynamic performance. Density functional theory calculations revealed that the introduction of Cu and resulting sulfur vacancies can induce electron redistribution, achieving favorable photogenerated electrons. After entering cells through endocytosis, the TPZ@Cu-SnS2-x /PLL nanocomposites show the pH responsivity property for the release of the TPZ selectively within the acidic TME, and the released Cu2+ can first interact with local glutathione (GSH) to deplete GSH with the production of Cu+ . Subsequently, the Cu+ -mediated Fenton-like reaction can decompose local hydrogen peroxide into hydroxyl radicals, which can also be promoted by hyperthermia derived from the photothermal effect for tumor cell apoptosis. The integration of photoacoustic/computed tomography imaging-guided NIR phototherapy, TPZ-induced chemotherapy, and GSH-elimination/hyperthermia enhanced chemodynamic therapy results in synergistic therapeutic outcomes without obvious systemic toxicity in vivo.

Synergizing Pyroelectric Catalysis and Enzyme Catalysis: Establishing a Reciprocal and Synergistic Model to Enhance Anti-Tumor Activity.

Nanozyme activity is greatly weakened by the microenvironment and multidrug resistance of tumor cells. Hence, a bi-catalytic nanoplatform, which promotes the anti-tumor activity through "charging empowerment" and "mutual complementation" processes involved in enzymatic and pyroelectric catalysis, by loading ultra-small nanoparticles (USNPs) of pyroelectric ZnSnO3 onto MXene nanozyme (V2CTx nanosheets), is developed. Here, the V2CTx nanosheets exhibit enhanced peroxidase activity by reacting V3+ with H2O2 to generate toxic ·OH, accelerated by the near-infrared (NIR) light mediated heat effect. The resulting V4+ is then converted to V3+ by oxidizing endogenous glutathione (GSH), realizing an enzyme-catalyzed cycle. However, the cycle will lose its persistence once GSH is insufficient; nevertheless, the pyroelectric charges generated by ZnSnO3 USNPs continuously support the V4+/V3+ conversion and ensure nanoenzyme durability. Moreover, the hyperthermia arising from the V2CTx nanosheets by NIR irradiation results in an ideal local temperature gradient for the ZnSnO3 USNPs, giving rise to an excellent pyroelectric catalytic effect by promoting band bending. Furthermore, polarized charges increase the tumor cell membrane permeability and facilitate nanodrug accumulation, thereby resolving the multidrug resistance issue. Thus, the combination of pyroelectric and enzyme catalysis together with the photothermal effect solves the dilemma of nanozymes and improves the antitumor efficiency.

Architecture of Vanadium-Based MXene Dysregulating Tumor Redox Homeostasis for Amplified Nanozyme Catalytic/Photothermal Therapy.

Taking the significance of the special microenvironment for tumor cell survival into account, disrupting tumor redox homeostasis is highly prospective for improving therapeutic efficacy. Herein, a multifunctional 2D vanadium-based MXene nanoplatform, V4 C3 /atovaquone@bovine albumin (V4 C3 /ATO@BSA, abbreviated as VAB) has been elaborately constructed for ATO-enhanced nanozyme catalytic/photothermal therapy. The redox homeostasis within the tumor cells is eventually disrupted, showing a remarkable anti-tumor effect. The VAB nanoplatform with mixed vanadium valence states can induce a cascade of catalyzed reactions in the tumor microenvironment, generating plenty of reactive oxygen species (ROS) with effective glutathione consumption to amplify oxidative stress. Meanwhile, the stable and strong photothermal effect of VAB under near-infrared irradiation not only causes the necrosis of tumor cells, but also improves its peroxidase-like activity. In addition, the release of ATO can effectively alleviate endogenous oxygen consumption to limit triphosadenine formation and inhibit mitochondrial respiration. As a result, the expression of heat shock proteins is effectively suppressed to overcome thermoresistance and the production of ROS can be further promoted due to mitochondrial injury. Moreover, VAB also presents high photoacoustic and photothermal imaging performances. In brief, the multifunctional nanoplatform can provide ATO-enhanced nanozyme catalytic/photothermal therapy with broadening the biomedical applications of vanadium-based MXene.

Brain white matter alterations in young adult male patients with childhood-onset growth hormone deficiency: a diffusion tensor imaging study.

PURPOSE: This study aimed to detect white matter changes and different effects of thyroid hormone on the white matter integrity in young adult male patients with childhood-onset growth hormone deficiency (CO-GHD), compared with healthy people. METHODS: Magnetic resonance imaging (structural imaging and diffusion tensor imaging) was performed in 17 young adult male patients with CO-GHD and 17 healthy male controls. The white matter volume, mean diffusivity (MD) values and fractional anisotropy (FA) values were quantified and compared between two groups (CO-GHD group vs. control group). We assessed the interaction effects between thyroid hormone and groups (CO-GHD group vs. control group) on white matter integrity. RESULTS: Patients with CO-GHD exhibited similar white matter volumes compared with controls. However, compared with the controls, patients with CO-GHD showed a significant reduction in FA values in six clusters and a substantial increase in MD values in four clusters, mainly involving the corticospinal tracts, corpus callosum and so on. Moreover, after correcting for insulin-like growth factor-1 levels, the significant interaction effects between groups (CO-GHD group vs. control group) and serum free thyroxine levels on MD values were noted in three clusters, mainly involving in superior longitudinal fasciculus and sagittal stratum. CONCLUSION: In conclusion, young males with CO-GHD showed white matter changes in multiple brain regions and different effects of thyroid hormone on the white matter integrity.

Influencing factors of hospitalization in maintenance haemodialysis outpatients after a diagnosis of COVID-19.

BACKGROUND: The clinical manifestations of maintenance haemodialysis (MHD) outpatients diagnosed with coronavirus disease 2019 (COVID-19) are highly heterogeneous. They are prone to progress to severe conditions, and they often require hospitalization. To better guide the management of MHD outpatients, this retrospective observational study assessed risk factors for hospitalization of MHD patients after a diagnosis of COVID-19. METHODS: The demographic data, comorbidities, laboratory indicators and imaging data of 128 MHD outpatients at our haemodialysis centre with confirmed COVID-19 infection from December 2022 to January 2023 were collected. The relationships between these factors and hospitalization of patients were analyzed. RESULTS: Among the 128 patients, 25 (19.53%) were hospitalized. One of the 25 inpatients was mechanically ventilated, and two of them died. Multivariate logistic regression analysis showed that the hospitalization rate was correlated with age, comorbid diabetes and peripheral blood lymphocyte count. CONCLUSION: Older age, comorbid diabetes and lower lymphocyte count are important risk factors for hospitalization of MHD outpatients after a diagnosis of COVID-19. Focusing on these factors may help in early identification of patients who may need to be admitted due to potential disease progression.

Advanced glycation end products impair bone marrow mesenchymal stem cells osteogenesis in periodontitis with diabetes via FTO-mediated N6-methyladenosine modification of sclerostin.

BACKGROUND: Diabetes mellitus (DM) and periodontitis are two prevalent diseases with mutual influence. Accumulation of advanced glycation end products (AGEs) in hyperglycemia may impair cell function and worsen periodontal conditions. N6-methyladenosine (m6A) is an important post-transcriptional modification in RNAs that regulates cell fate determinant and progression of diseases. However, whether m6A methylation participates in the process of periodontitis with diabetes is unclear. Thus, we aimed to investigate the effects of AGEs on bone marrow mesenchymal stem cells (BMSCs), elucidate the m6A modification mechanism in diabetes-associated periodontitis. METHODS: Periodontitis with diabetes were established by high-fat diet/streptozotocin injection and silk ligation. M6A modifications in alveolar bone were demonstrated by RNA immunoprecipitation sequence. BMSCs treated with AGEs, fat mass and obesity associated (FTO) protein knockdown and sclerostin (SOST) interference were evaluated by quantitative polymerase chain reaction, western blot, immunofluorescence, alkaline phosphatase and Alizarin red S staining. RESULTS: Diabetes damaged alveolar bone regeneration was validated in vivo. In vitro experiments showed AGEs inhibited BMSCs osteogenesis and influenced the FTO expression and m6A level in total RNA. FTO knockdown increased the m6A levels and reversed the AGE-induced inhibition of BMSCs differentiation. Mechanically, FTO regulated m6A modification on SOST transcripts, and AGEs affected the binding of FTO to SOST transcripts. FTO knockdown accelerated the degradation of SOST mRNA in presence of AGEs. Interference with SOST expression in AGE-treated BMSCs partially rescued the osteogenesis by activating Wnt Signaling. CONCLUSIONS: AGEs impaired BMSCs osteogenesis by regulating SOST in an m6A-dependent manner, presenting a promising method for bone regeneration treatment of periodontitis with diabetes.

Results of Medial Patellofemoral Ligament Reconstruction with and without Tibial Tubercle Transfer in Patellar Instability: A Systematic Review and Meta-Analysis.

The optimal surgical intervention for lateral patellar instability remains a topic of controversy despite satisfactory clinical outcomes and low re-dislocation rates reported in numerous studies following medial patellofemoral ligament reconstruction (MPFLR) with and without tibial tubercle transfer (TTT). The purpose of this systematic review and meta-analysis is to investigate the hypothesis that combining MPFLR with TTT provides reduced complication rates and improved clinical outcomes to isolated MPFLR in patients with lateral patellar instability. We conducted a comprehensive systematic review and meta-analysis of comparative trials involving MPFLR with and without TTT, sourcing data from PubMed, the Cochrane Library, Embase, and Web of Science. The primary clinical outcomes analyzed included the Kujala score, the Lysholm score, complication rates, and the Caton-Deschamps index (CDI). Random or fixed effects were used for the meta-analysis. Postoperatively, there were no significant differences observed in the Kujala and Lysholm scores between MPFLR and MPFLR + TTT (p = 0.053). At the final follow-up, the CDI had decreased 0.015 (95% CI -0.044, 0.013; p = 0.289) points in the MPFLR group, with no statistical significance. In contrast, the MPFLR + TTT group demonstrated a significant decrease of 0.207 (95% CI -0.240, -0.174; p = 0.000) points in CDI. Notably, the complication rate was higher in the MPFLR + TTT group compared to the MPFLR-only group (RR = 2.472; 95% CI 1.638, 3.731; p = 0.000). Both MPFLR and MPFLR + TTT procedures yield significant improvements in the Kujala and Lysholm scores. However, the MPFLR + TTT approach results in an apparent improvement in CDI and corrects patellar maltracking, particularly in cases involving high tibial tuberosity-trochlear groove (TT-TG) (>20 mm) or patella alta (CDI > 1.2), while MPFLR alone cannot. It is essential to consider the higher complication rate of MPFLR + TTT, which suggests that MPFLR alone may be sufficient for patients without high TT-TG or patella alta.

Inhibition of neutrophil extracellular trap formation ameliorates neuroinflammation and neuronal apoptosis via STING-dependent IRE1α/ASK1/JNK signaling pathway in mice with traumatic brain injury.

BACKGROUND: Neuroinflammation is one of the most important pathogeneses in secondary brain injury after traumatic brain injury (TBI). Neutrophil extracellular traps (NETs) forming neutrophils were found throughout the brain tissue of TBI patients and elevated plasma NET biomarkers correlated with worse outcomes. However, the biological function and underlying mechanisms of NETs in TBI-induced neural damage are not yet fully understood. Here, we used Cl-amidine, a selective inhibitor of NETs to investigate the role of NETs in neural damage after TBI. METHODS: Controlled cortical impact model was performed to establish TBI. Cl-amidine, 2'3'-cGAMP (an activator of stimulating Interferon genes (STING)), C-176 (a selective STING inhibitor), and Kira6 [a selectively phosphorylated inositol-requiring enzyme-1 alpha [IRE1α] inhibitor] were administrated to explore the mechanism by which NETs promote neuroinflammation and neuronal apoptosis after TBI. Peptidyl arginine deiminase 4 (PAD4), an essential enzyme for neutrophil extracellular trap formation, is overexpressed with adenoviruses in the cortex of mice 1 day before TBI. The short-term neurobehavior tests, magnetic resonance imaging (MRI), laser speckle contrast imaging (LSCI), Evans blue extravasation assay, Fluoro-Jade C (FJC), TUNEL, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), western blotting, and quantitative-PCR were performed in this study. RESULTS: Neutrophils form NETs presenting in the circulation and brain at 3 days after TBI. NETs inhibitor Cl-amidine treatment improved short-term neurological functions, reduced cerebral lesion volume, reduced brain edema, and restored cerebral blood flow (CBF) after TBI. In addition, Cl-amidine exerted neuroprotective effects by attenuating BBB disruption, inhibiting immune cell infiltration, and alleviating neuronal death after TBI. Moreover, Cl-amidine treatment inhibited microglia/macrophage pro-inflammatory polarization and promoted anti-inflammatory polarization at 3 days after TBI. Mechanistically, STING ligand 2'3'-cGAMP abolished the neuroprotection of Cl-amidine via IRE1α/ASK1/JNK signaling pathway after TBI. Importantly, overexpression of PAD4 promotes neuroinflammation and neuronal death via the IRE1α/ASK1/JNK signaling pathway after TBI. However, STING inhibitor C-176 or IRE1α inhibitor Kira6 effectively abolished the neurodestructive effects of PAD4 overexpression after TBI. CONCLUSION: Altogether, we are the first to demonstrate that NETs inhibition with Cl-amidine ameliorated neuroinflammation, neuronal apoptosis, and neurological deficits via STING-dependent IRE1α/ASK1/JNK signaling pathway after TBI. Thus, Cl-amidine treatment may provide a promising therapeutic approach for the early management of TBI.

Low-intensity pulsed ultrasound regulates osteoblast-osteoclast crosstalk via EphrinB2/EphB4 signaling for orthodontic alveolar bone remodeling.

Background: The limited regenerative potential of periodontal tissue remains a challenge in orthodontic treatment, especially with respect to alveolar bone remodeling. The dynamic balance between the bone formation of osteoblasts and the bone resorption of osteoclasts controls bone homeostasis. The osteogenic effect of low-intensity pulsed ultrasound (LIPUS) is widely accepted, so LIPUS is expected to be a promising method for alveolar bone regeneration. Osteogenesis is regulated by the acoustic mechanical effect of LIPUS, while the cellular perception, transduction mode and response regulation mechanism of LIPUS stimuli are still unclear. This study aimed to explore the effects of LIPUS on osteogenesis by osteoblast-osteoclast crosstalk and the underlying regulation mechanism. Methods: The effects of LIPUS on orthodontic tooth movement (OTM) and alveolar bone remodeling were investigated via rat model by histomorphological analysis. Mouse bone marrow mesenchymal stem cells (BMSCs) and bone marrow monocytes (BMMs) were purified and used as BMSC-derived osteoblasts and BMM-derived osteoclasts, respectively. The osteoblast-osteoclast co-culture system was used to evaluate the effect of LIPUS on cell differentiation and intercellular crosstalk by Alkaline phosphatase (ALP), Alizarin Red S (ARS), tartrate-resistant acid phosphatase (TRAP) staining, real-time quantitative PCR, western blotting and immunofluorescence. Results: LIPUS was found to improve OTM and alveolar bone remodeling in vivo, promote differentiation and EphB4 expression in BMSC-derived osteoblasts in vitro, particularly when cells were directly co-cultured with BMM-derived osteoclasts. LIPUS enhanced EphrinB2/EphB4 interaction between osteoblasts and osteoclasts in alveolar bone, activated the EphB4 receptor on osteoblasts membrane, transduced LIPUS-related mechanical signals to the intracellular cytoskeleton, and gave rise to the nuclear translocation of YAP in Hippo signaling pathway, thus regulating cell migration and osteogenic differentiation. Conclusions: This study shows that LIPUS modulates bone homeostasis by osteoblast-osteoclast crosstalk via EphrinB2/EphB4 signaling, which benefits the balance between OTM and alveolar bone remodeling.

Gallic acid-grafted chitosan antibacterial hydrogel incorporated with polydopamine-modified hydroxyapatite for enhancing bone healing.

An open critical-size bone defect is a major medical problem because of the difficulty in self-healing, leading to an increased risk of bacterial infection owing to wound exposure, resulting in treatment failure. Herein, a composite hydrogel was synthesized by chitosan, gallic acid, and hyaluronic acid, termed "CGH." Hydroxyapatite was modified with polydopamine (PDA@HAP) and introduced to CGH to obtain a mussel-inspired mineralized hydrogel (CGH/PDA@HAP). The CGH/PDA@HAP hydrogel exhibited excellent mechanical performances, including self-healing and injectable properties. Owing to its three-dimensional porous structure and polydopamine modifications, the cellular affinity of the hydrogel was enhanced. When adding PDA@HAP into CGH, Ca2+ and PO4 3- could release and then promoted differentiation of BMSCs into osteoblasts. Without any osteogenic agent or stem cells, the area of new bone at the site of defect was enhanced and the newly formed bone had a dense trabecular structure after implanting of the CGH/PDA@HAP hydrogel for 4 and 8 weeks. Moreover, the growth of Staphylococcus aureus and Escherichia coli was effectively inhibited through the grafting of gallic acid onto chitosan. Above, this study provides a reasonable alternative strategy to manage open bone defects.

Neutrophil extracellular traps aggravate neuronal endoplasmic reticulum stress and apoptosis via TLR9 after traumatic brain injury.

Endoplasmic reticulum (ER) stress and ER stress-mediated apoptosis play an important role during secondary brain damage after traumatic brain injury (TBI). Increased neutrophil extracellular traps (NETs) formation has been demonstrated to be associated with neurological damage after TBI. However, the correlation between ER stress and NETs remains unclear, and the specific function of NETs in neurons has not been defined. In this study, we found that the levels of NETs circulating biomarkers were remarkably elevated in the plasma of TBI patients. We then inhibited NETs formation by peptidylarginine deiminase 4 (PAD4, a critical enzyme for NETs formation) deficiency and discovered that ER stress activation and ER stress-mediated neuronal apoptosis were reduced. The degradation of NETs via DNase I showed similar outcomes. Furthermore, overexpression of PAD4 aggravated neuronal ER stress and ER stress-associated apoptosis, while TLR9 antagonist administration abrogated the damage caused by NETs. In addition to in vivo experiments, in vitro experiments revealed that treatment with a TLR9 antagonist alleviated NETs-induced ER stress and apoptosis in HT22 cells. Collectively, our results indicated that ER stress as well as the accompanying neuronal apoptosis can be ameliorated by disruption of NETs and that suppression of the TLR9-ER stress signaling pathway may contribute to positive outcomes after TBI.

2D Piezoelectric BiVO4 Artificial Nanozyme with Adjustable Vanadium Vacancy for Ultrasound Enhanced Piezoelectric/Sonodynamic Therapy.

Increasing the yield of reactive oxygen species (ROS) to enhance oxidative stress in cells is an eternal goal in cancer therapy. In this study, BiVO4 artificial nanozyme is developed with adjustable vanadium vacancy for ultrasound (US) enhanced piezoelectric/sonodynamic therapy. Under US excitation, the vanadium vacancy-rich BiVO4 nanosheets (abbreviated Vv -r BiVO4 NSs) facilitate the generation of a large number of electrons to improve the ROS yield. Meanwhile, the mechanical strain imposed by US irradiation makes the Vv -r BiVO4 NSs display a typical piezoelectric response, which tilts the conduction band to be more negative and the valance band more positive than the redox potentials of O2 /O2 •- and H2 O/·OH, boosting the efficiency of ROS generation. Both density functional theory calculations and experiments confirm that the introduction of cationic vacancy can improve the sonodynamic effect. As expected, Vv -r BiVO4 NSs have better peroxidase enzyme catalytic and glutathione depletion activities, resulting in increased intracellular oxidative stress. This triple amplification strategy of oxidative stress induced by US substantially inhibits the growth of cancer cells. The work may open an avenue to achieve a synergetic therapy by introducing cationic vacancy, broadening the biomedical use of piezoelectric materials.

A retrospective case series of the treatment of spontaneous quadriceps tendon rupture in patients with uremia and secondary hyperparathyroidism.

Background: Spontaneous quadriceps tendon rupture (QTR) is a rare complication of uremia. Secondary hyperparathyroidism (SHPT) is considered the leading cause of QTR in uremia patients. QTR in patients with uremia and SHPT are treated with active surgical repair along with the treatment of SHPT using medication or parathyroidectomy (PTX). The impact of PTX for SHPT on tendon healing remains unclear. The purpose of this study was to introduce surgical procedures for QTR and to determine the functional recovery of the repaired quadriceps tendon (QT) after PTX. Methods: Between Jan 2014 and Dec 2018, eight uremia patients underwent PTX after a ruptured QT was repaired by figure-of-eight trans-osseous sutures with an overlapping tightening suture technique. Biochemical indices were measured before and one year after PTX to evaluate the control of SHPT. The changes in bone mineral density (BMD) were determined by comparing x-ray images at pre-PTX and during follow-up. The assessment of the functional recovery of the repaired QT was conducted at the last follow-up using multiple functional parameters. Results: Eight patients (fourteen tendons) were retrospectively evaluated at an average follow-up of 3.46 ± 1.37 years after PTX. ALP and iPTH levels one year after PTX were significantly lower than at pre-PTX (P = 0.017, P < 0.001, respectively). Although there was no statistical differences compared to pre-PTX, serum phosphorus levels decreased and returned to normal one year after PTX (P = 0.101). BMD significantly increased at the last follow-up compared to pre-PTX. The average Lysholm score was 73.5 ± 11.07 and the average Tegner activity score was 2.63 ± 1.06. The active knee ROM after repair averaged an extension of 2.85 ± 3.78° to a flexion angle of 113.21 ± 10.12°. The quadriceps muscle strength was grade IV and the mean Insall-Salvati index was 0.93 ± 0.10 in all of the knees with tendon ruptures. All patients were able to walk without external help. Conclusions: Figure-of-eight trans-osseous sutures with an overlapping tightening suture technique is an economical and effective treatment for spontaneous QTR in patients with uremia and SHPT. PTX may promote tendon-bone healing in patients with uremia and SHPT.

Bone marrow stimulation in arthroscopic rotator cuff repair is a cost-effective and straightforward technique to reduce retear rates: A systematic review and meta-analysis.

Background: Bone marrow stimulation (BMS) has been considered a well-established method for treating knee and ankle osteochondral lesions. Some studies have also shown that BMS can promote healing of the repaired tendon and enhance biomechanical properties during rotator cuff repair. Our purpose was to compare the clinical outcomes of arthroscopic repair rotator cuff (ARCR) with and without BMS. Methods: A systematic review with meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed, Embase, Web of Science, Google scholar, ScienceDirect, and the Cochrane Library were searched from inception to March 20, 2022. Data on retear rates, shoulder functional outcomes, visual analog score and range of motion were pooled and analyzed. Dichotomous variables were presented as odds ratios (OR), and continuous variables were presented as mean differences (MD). Meta-analyses were conducted with Review Manager 5.3. Results: Eight studies involving 674 patients were included, with mean follow-up period ranging from 12 to 36.8 months. Compared to ARCR alone, the intraoperative combination of the BMS resulted in lower retear rates (P < 0.0001), but showed similar results in Constant score (P = 0.10), University of California at Los Angeles (UCLA) score (P = 0.57), American Shoulder and Elbow Surgeons (ASES) score (P = 0.23), Disabilities of the Arm, Shoulder and Hand (DASH) score (P = 0.31), VAS (visual analog score) score (P = 0.34), and range of motion (ROM) (forward flexion, P = 0.42; external rotation, P = 0.21). After sensitivity analyses and subgroup analyses, no significant changes in statistical results were observed. Conclusion: Compared to ARCR alone, the combination of intraoperative BMS can significantly reduce the retear rates, but showed similar short-term results in functional outcomes, ROM and pain. Better clinical outcomes are anticipated in the BMS group by improving structural integrity during long-term follow-up. Currently, BMS may be a viable option in ARCR based on its straightforward and cost-effective advantages. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022323379.

Knocking down GALNT6 promotes pyroptosis of pancreatic ductal adenocarcinoma cells through NF-κB/NLRP3/GSDMD and GSDME signaling pathway.

Background: Pancreatic ductal adenocarcinoma (PDAC), the most prevalent type of pancreatic cancer, is a highly lethal malignancy with poor prognosis. Polypeptide N-acetylgalactosaminyltransferase-6 (GALNT6) is frequently overexpressed in PDAC. However, the role of GALNT6 in the PDAC remains unclear. Methods: The expression of GALNT6 in pancreatic cancer and normal tissues were analyzed by bioinformatic analyses and immunohistochemistry. CCK8 and colony formation were used to detect cell proliferation. Flow cytometry was applied to detect cell cycle.The pyroptosis was detected by scanning electron microscopy. The mRNA expression was detected by qRT-PCR. The protein expression and localization were detected by western blot and immunofluorescence assay. ELISA was used to detect the levels of inflammatory factors. Results: The expression of GALNT6 was associated with advanced tumor stage, and had an area under curve (AUC) value of 0.919 in pancreatic cancer based on the cancer genome atlas (TCGA) dataset. Knockdown of GALNT6 inhibited cell proliferation, migration, invasion and cell cycle arrest of PDAC cells. Meanwhile, knockdown of GALNT6 increased the expression levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-18 (IL-18), the release of inflammasome and an increasing of Gasdermin D (GSDMD), N-terminal of GSDMD (GSDMD-N), Gasdermin E (GSDME) and N-terminal of GSDME (GSDME-N) in PDAC cells. GALNT6 suppressed the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and GSDMD by glycosylation of NF-κB and inhibiting the nucleus localization of NF-κB. Additionally, GALNT6 promotes the degradation of GSDME by O-glycosylation. Conclusion: We found that GALNT6 is highly expressed in pancreatic cancer and plays a carcinogenic role. The results suggested that GALNT6 regulates the pyroptosis of PDAC cells through NF-κB/NLRP3/GSDMD and GSDME signaling. Our study might provides novel insights into the roles of GALNT6 in PDAC progression.

Dual Nanozyme-Driven PtSn Bimetallic Nanoclusters for Metal-Enhanced Tumor Photothermal and Catalytic Therapy.

Specific generation of reactive oxygen species (ROS) within tumors in situ catalyzed by nanozymes is a promising strategy for cancer therapeutics. However, it remains a significant challenge to fabricate highly efficient nanozymes acting in the tumor microenvironment. Herein, we develop a bimetallic nanozyme (Pt50Sn50) with the photothermal enhancement of dual enzymatic activities for tumor catalytic therapy. The structures and activities of PtSn bimetallic nanoclusters (BNCs) with different Sn content are explored and evaluated systematically. Experimental comparisons show that the Pt50Sn50 BNCs exhibit the highest activities among all those investigated, including enzymatic activity and photothermal property, due to the generation of SnO2-x with oxygen vacancy (Ovac) sites on the surface of Pt50Sn50 BNCs. Specifically, the Pt50Sn50 BNCs exhibit photothermal-enhanced peroxidase-like and catalase-like activities, as well as a significantly enhanced anticancer efficacy in both multicellular tumor spheroids and in vivo experiments. Due to the high X-ray attenuation coefficient and excellent light absorption property, the Pt50Sn50 BNCs also show dual-mode imaging capacity of computed tomography and photoacoustic imaging, which could achieve in vivo real-time monitoring of the therapeutic process. Therefore, this work will advance the development of noble-metal nanozymes with optimal composition for efficient tumor catalytic therapy.