Stepwise-targeting and hypoxia-responsive liposome AMVY@NPs carrying siYAP and verteporfin for glioblastoma therapy.

BACKGROUND: The Hippo pathway is a conserved tumour suppressor signalling pathway, and its dysregulation is often associated with abnormal cell growth and tumorigenesis. We previously revealed that the transcriptional coactivator Yes-associated protein (YAP), the key effector of the Hippo pathway, is a molecular target for glioblastoma (GBM), the most common malignant brain tumour. Inhibiting YAP with small interfering RNA (siYAP) or the specific inhibitor verteporfin (VP) can diminish GBM growth to a certain degree. RESULTS: In this study, to enhance the anti-GBM effect of siYAP and VP, we designed stepwise-targeting and hypoxia-responsive liposomes (AMVY@NPs), which encapsulate hypoxia-responsive polymetronidazole-coated VP and DOTAP adsorbed siYAP, with angiopep-2 (A2) modification on the surface. AMVY@NPs exhibited excellent blood‒brain barrier crossing, GBM targeting, and hypoxia-responsive and efficient siYAP and VP release properties. By inhibiting the expression and function of YAP, AMVY@NPs synergistically inhibited both the growth and stemness of GBM in vitro. Moreover, AMVY@NPs strongly inhibited the growth of orthotopic U87 xenografts and improved the survival of tumour-bearing mice without adverse effects. CONCLUSION: Specific targeting of YAP with stepwise-targeting and hypoxia-responsive liposome AMVY@NPs carrying siYAP and VP efficiently inhibited GBM progression. This study provides a valuable drug delivery platform and creative insights for molecular targeted treatment of GBM in the future.

Enhancement of chitosan-based film physicochemical and storage properties by interaction with proanthocyanidin and natural deep eutectic solvent.

Deep eutectic solvent (DES) has been recognized as a promising plasticizer for the preparation of biodegradable food packaging films. In addition, DES-plasticized chitosan (CS) films could also serve as a favorable carrier for loading active components. In this work, a ternary composite film was fabricated by plasticizing chitosan with DES and the active ingredient proanthocyanidin (PA) was used as a cross-linking agent. The incorporation of PAs significantly enhanced the toughness, elasticity, and hydrophobicity of the ternary CS-DES-PA composite films. It achieved antioxidant and bacteriostatic functions. In particular, the ternary CS-DES-PA composite films had a thickness of 0.16 ± 0.01 µm, a tensile strength of 2.63 ± 0.48 MPa, and an elongation about 73.22 %. They also have improved water resistance, UV blocking, with a high-water contact angle of 88.4° and a low water swelling of 5 % on the surface of the film. Meanwhile, the PAs in the film could slow down the browning of litchi fruits. This ternary blended film (CS-DES-PA) achieves better compatibility of the active ingredient in the film-forming substrate. It also provides a green and biodegradable packaging material for food packaging.

Construction of Fe Nanoparticles Interfacial Layer on Micron Al Surface: Boosting the Efficient Energy Release of High-Energy DAP-4 as a Gradient Catalyst.

The high-energy (H2dabco)[NH4(ClO4)3] (DAP-4) with excellent energetic performance attracts wide attention from researchers. The investigation of its interaction with the Aluminum (Al) is of great importance. However, the higher ignition threshold of DAP-4 and the dense oxide layer (Al2O3) of Al severely limit the energy release efficiency of Al/DAP-4. In this study, a new idea to is first proposed to improve and adjust the thermal decomposition and combustion performance of Al/DAP-4 by constructing a highly dispersed iron (Fe) nanoparticle interfacial layer. It acts as a gradient catalyst to promote the thermal decomposition and combustion of DAP-4 and Al, and it also act as an oxygen transport channel to promote the contact and reaction of oxidizing gases with the internal reactive Al powder. It reduces the thermal decomposition temperature of Al@Fe-3/DAP-4 from 386.30 °C (Al/DAP-4) to 349.48 °C and leads to the vigorous combustion. Theoretical calculations show that Fe nanoparticle interfacial layer can facilitate the transport of oxygen through the established oxygen transport channels, and it can also significantly improve the energetic properties of Al@Fe-3/DAP-4 composites. In conclusion, the new approach is proposed to improve the performance of metal fuel/oxidizer composites by constructing interfacial layers, which is expected to promote their practical applications.

Clinical outcome after open-wedge high tibial osteotomy: comparison of double-triangle locking compression plate (DT-LCP) and T-shaped locking compression plate (T-LCP).

BACKGROUND: The objective of this study was to compare the clinical outcomes of two internal fixation methods for high tibial osteotomy (HTO): double-triangle locking compression plate (DT-LCP) and T-shaped locking compression plate (T-LCP). METHODS: 202 adult patients in our hospital between January 2018 and December 2021 were included and followed up for at least one year: group 1(DT-LCP, 98 patients) and group 2 (T-LCP, 104 patients). Detailed information on demographics, preoperative and postoperative follow-up, surgical procedures, and complications were collected. The information of the International Knee Documentation Committee Knee Evaluation Form (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were collected before surgery and at the last follow-up. RESULTS: A total of 202 patients were included in the per-protocol analysis. No significant difference was found in terms of demographic data between groups, except for age and BMI. Clinically relevant improvements in knee pain were reached up to last follow-up after the operation in both groups. The mean pain scores (KOOS, WOMAC) at the final follow-up were significantly higher among group 1 compared to group 2 (P = 0.040 and P = 0.023). Furthermore, the DT-LCP internal fixation exerted more excellent effects on other symptoms, function and quality of life than T-LCP internal fixation. CONCLUSIONS: Our study demonstrated that DT-LCP provided better clinical performance due to its implant irritant pain, compared with T-LCP. Thus, DT-LCP is a feasible alternative for the fixation of OW-HTO.

Is single-stage bilateral medial opening wedge high tibial osteotomy advisable?

PURPOSE: To validate the safety and clinical results of single-stage bilateral versus unilateral medial opening wedge high tibial osteotomy (HTO). METHODS: A propensity-matched cohort study was performed from March 2020 to March 2021 in our medical center. Data were prospectively collected. Including 34 patients who underwent single-stage bilateral medial opening HTO(SSBHTO), and 68 cases in the unilateral group. Propensity-matched ration was 2:1 based on age, sex, and body mass index using R software. Comparisons of the length of hospital stay, operative time, blood loss, postoperative adverse events, 90-day readmission rate, conversion to TKA rate, self-reported VAS and WOMAC scores were made to investigate the safety and clinical results of bilateral HTO. RESULTS: The mean length of hospital stay was 7.36 ± 2.23 days for SSBHTO and 7 days (IQR, 3 days; range, 4 to 23 days) for the unilateral group (P = 0.219). The mean operative time was 144 ± 47 min for bilateral HTO and 105(37.5) mins for a unilateral OWHTO (P < 0.001). The mean blood loss was 150(100) ml for SSBHTO and 100(50) ml for unilateral OWHTO (P < 0.001). There were no significant difference of the adverse events and 90-day readmission rate between two groups. No failed HTO or conversion to knee arthroplasty were observed at the end of follow-up. VAS, pain, stiffness, and functional scores of the WOMAC scale were essentially comparable of two groups one year after surgery (P > 0.05). CONCLUSIONS: A single-stage bilateral medial opening wedge high tibial osteotomy is advisable for patients with knee osteoarthritis. Patients benefit from avoiding secondary anesthesia, postoperative complications, and substantial cost savings. LEVEL OF EVIDENCE: Therapeutic Level III.

In Situ Structural Densification of Hydrogel Network and Its Interface with Electrodes for High-Performance Multimodal Artificial Skin.

The multisensory responsiveness of hydrogels positions them as promising candidates for artificial skin, whereas the mismatch of modulus between soft hydrogels and hard electrodes as well as the poor adhesion and conductance at the interface greatly impairs the stability of electronics devices. Herein, we propose an in situ postprocessing approach utilizing electrochemical reactions between metals (Zn, etc.) and hydrogels to synergistically achieve strong adhesion of the hydrogel-electrode interface, low interfacial impedance, and local strain isolation due to the structural densification of the hydrogel network. The mechanism is that Zn electrochemically oxidizes to Zn2+ and injects into the hydrogel, gradually forming a mechanically interlocked structure, Zn2+-polymer dual-helix structural nodes, and a high-modulus ZnO from the surface to the interior. Compared to untreated samples, the treated sample displays 8.7 times increased interfacial adhesion energy between the hydrogel and electrode (87 J/m2), 95% decreased interfacial impedance (218.8 Ω), and a high-strain isolation efficiency (εtotal/εisolation > 400). Akin to human skin, the prepared sensor demonstrates multimodal sensing capabilities, encompassing highly sensitive strain perception and simultaneous perception of temperature, humidity, and oxygen content unaffected by strain interference. This easy on-chip preparation of hydrogel-based multimodal sensor array shows great potential for health and environment monitoring as artificial skin.

Antitumor Effect and Immunomodulatory Mechanism of "Oncolytic Extracellular Vesicles".

Enhancing the antitumor immune response and targeting ability of oncolytic viruses will improve the effect of tumor immunotherapy. Through infecting neural stem cells (NSCs) with a capsid dual-modified oncolytic adenovirus (CRAd), we obtained and characterized the "oncolytic extracellular vesicles" (CRAdEV) with improved targeted infection and tumor killing activity compared with CRAd. Both ex vivo and in vivo studies revealed that CRAdEV activated innate immune cells and importantly enhanced the immunomodulatory effect compared to CRAd. We found that CRAdEV effectively increased the number of DCs and activated CD4+ and CD8+ T cells, significantly increased the number and activation of B cells, and produced higher levels of tumor-specific antibodies, thus eliciting enhanced antitumor activity compared with CRAd in a B16 xenograft immunocompetent mice model. This study provides a novel approach to oncolytic adenovirus modification and demonstrates the potential of "oncolytic extracellular vesicles" in antitumor immunotherapy.

Dissecting causal relationships between primary biliary cholangitis and extrahepatic autoimmune diseases based on Mendelian randomization.

As an autoimmune disease, up to 73% of patients with primary biliary cholangitis (PBC) have a combination of extrahepatic autoimmune diseases (EHAIDs); however, the causal relationship between PBC and EHAIDs is unclear. The genome-wide association analyses provided 14 GWAS data for PBC and EHAIDs, and bidirectional, two-sample MR analyses were performed to examine the relationship between PBC and EHAIDs. The analysis using MR provides a strong and meaningful estimation of the bidirectional correlation between PBC and 7 EHAIDs: rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, autoimmune hypothyroidism, inflammatory bowel disease and ulcerative colitis of its types. In addition, PBC increases the risk of autoimmune thyroid diseases such as autoimmune hyperthyroidism and Graves' disease, as well as multiple sclerosis and psoriasis. Additionally, PBC is identified as a risk factor for Crohn's disease and Celiac disease. Based on genetic evidence, there may be connections between PBC and specific EHAIDs: not all coexisting EHAIDs induce PBC, and vice versa. This underscores the significance of prioritizing PBC in clinical practice. Additionally, if any liver function abnormalities are observed during treatment or with EHAIDs, it is crucial to consider the possibility of comorbid PBC.

A robust multi-scale feature extraction framework with dual memory module for multivariate time series anomaly detection.

Although existing reconstruction-based multivariate time series anomaly detection (MTSAD) methods have shown advanced performance, most assume the training data is clean. When faced with noise or contamination in training data, they can also reconstruct the anomaly well, weakening the distinction between normal and anomaly. Some probabilistic generation-based methods have been used to address this issue because of their implicit robust structure to noise, but the training process and suppression of anomalous generalization are not stable. The recently proposed explicit method based on the memory module would also sacrifice the reconstruction effect of normal patterns, resulting in limited performance improvement. Moreover, most existing MTSAD methods use a single fixed-length window for input, which weakens their ability to extract long-term dependency. This paper proposes a robust multi-scale feature extraction framework with the dual memory module to comprehensively extract features fusing different levels of semantic information and lengths of temporal dependency. First, this paper designs consecutive neighboring windows as inputs to allow the model to extract local and long-term dependency information. Secondly, a dual memory-augmented encoder is proposed to extract global typical patterns and local common features. It ensures the reconstruction ability of normal data while suppressing the generalization of the anomaly. Finally, this paper proposes a multi-scale fusion module to fuse latent variables representing different levels of semantic information and uses the reconstructed latent variables to reconstruct samples for anomaly detection. Experimental results on five datasets from diverse domains show that the proposed method outperforms 16 typical baseline methods.

Research on the Influence of the Material Removal Profile of a Spherical Polishing Tool on the Mid-Spatial Frequency Errors of Optical Surfaces.

Elastic spherical polishing tools effectively conform to the polishing surface and exhibit high efficiency in the removal of materials, so they are extensively used in the sub-aperture polishing stages of optical components. However, their processing is often accompanied by significant mid-spatial frequency (MSF) errors, which critically degrade the performance of optical systems. To suppress the MSF errors generated during polishing with spherical tools, this study investigates the influence factor of MSF errors during the polishing process through an analysis of the convolution effect in material removal. A material removal profile model is established, and a uniform removal simulation is conducted to assess the influence of different shape material removal profiles on MSF errors. Simulation and experimental results show that a Gaussian-like shape material removal profile is more effective in suppressing the MSF errors during polishing compared to the "W" and trapezoidal shape material removal profiles. In addition, based on the characteristics of the RMS decreasing in a serrated trend with the decrease in path spacing, a path spacing optimization method considering the polishing efficiency is proposed to improve the polishing efficiency while controlling the MSF errors, and the effectiveness of the path spacing optimization method is verified by comparing the MSF error at the maximum theoretical path spacing and the path spacing that is less than this. Finally, the path spacing optimization method is used to polish single-crystal silicon to further illustrate its practicality.

Increased symptoms of stiffness after opening-wedge high tibial osteotomy are associated with worse postoperative knee function outcomes and lower patient satisfaction rate.

BACKGROUND: Symptoms of knee stiffness after open wedge high tibial osteotomy (OW-HTO) can significantly affect surgical effectiveness, but no studies have reported risk factors for knee stiffness after OW-HTO. METHODS: Patients treated with OW-HTO for the first time between 2018 and 2021 were included. Data were collected on patient demographics, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Short Form (SF) 12 scores, hip-knee-ankle angle (HKA) and patient satisfaction before and after surgery. Patients with worse WOMAC stiffness scores at 1 year were defined as the 'increased stiffness' group and the other cohort as the 'non-stiffness' group. The primary outcome of the study was to compare postoperative knee function scores (WOMAC and SF-12), HKA and patient satisfaction rate between the two groups. The secondary outcome was the use of logistic regression to analyze independent predictors of increased postoperative stiffness symptoms. RESULTS: At 1 year postoperatively, 95 (11.3%) patients had a significant increase in stiffness. Patients had significantly (p < .001) less improvement in pain, function, and total WOMAC scores, and SF-12 score than those in the non-stiffness group (n = 745). However, the differences in WOMAC and SF-12 scores in increased stiffness group at 1 year post-operatively were statistically significant (p < .001) compared to the non-stiffness group. There was no statistically significant difference in HKA in the increased stiffness group (172.9° ± 2.3°) compared to non-stiffness group (173.4° ± 2.6°) at 1 year postoperatively (p = .068). Patient satisfaction was significantly lower in the increased stiffness group (p < .001). Logistic regression analysis showed that diabetes (odds ratio (OR) 1.809, p = .034) and preoperative WOMAC stiffness score of 44 or less (OR 4.255 p < .001) were predictors of increased stiffness. CONCLUSIONS: Patients with increased stiffness after OW-HTO had worse functional outcomes and lower patient satisfaction rates and patients at risk of being in this group should be informed pre-operatively.

Enhancing acid stability of citral through internal structure modulation in nanostructured lipid carriers with solid lipids and phospholipids.

In this current study, the internal structure of nanostructured lipid carriers was modulated by phospholipids (lecithin PC, hydrogenated soybean phospholipid HPC) and solid lipids to achieve stable encapsulation of citral. The presence of high melting point HPC could construct α-crystalline type with more lattice defects and effectively inhibit ß-ization. The HPC group could maintain the particle size at 155.9-186.9 nm, the polydispersity index (PDI) at 0.182-0.321, the Zeta potential at -57.58 mV to -49.35 mV and the retention rate of citral at 91.33-98.49 % in the acidic environments of 2 mM and 20 mM hydrochloric acid solutions. The recrystallization index (RI) of NLC increased with the number of solid lipid ester bonds (from 3.57 % to 16.58 % in the PC group and from 0.82 % to 12.47 % in the HPC group). The results illustrated that the number of solid lipid ester bonds and the melting point of phospholipids affected crystallinity of the lipid matrix and thus the stability of encapsulated citral. Hydrogenated phospholipid with high melting points was more beneficial in stabilizing citral. The present study improved the acidic stability of citral and provided a new thought for the application of citral in acidic beverages.

The effect of font boldness, noise disturbance and time pressure on human error in the context of cloud change operation.

This study investigated the number of operator errors, task completion time, and workload of subjects at different levels by imposing conditions such as focused text boldness, noise disturbance, and time pressure to simulate a realistic cloud change business process in the laboratory. Results of the study showed that the text bolding of important content reduced the number of errors, whereas noise interference increased the number of errors. Text boldness only reduced the number of corrected errors, and noise interference only increased the number of uncorrected errors. Moreover, bolding was found to have different effects on the number of errors under different noise levels and time pressure levels, with text boldness significantly reducing the number of total errors only in quiet or low time pressure states. Time pressure had no effect on cloud change task error counts, but high time pressure resulted in higher subjective workload.

Operator error is one of the main causes of service failure, and reducing operator error in cloud change operations is of practical importance. In this study, we found focused text boldness could reduce operator errors, while noise could increase the number of errors. High time pressure would lead to a high workload.

Risk Factors and Dynamic Nomogram Development for Surgical Site Infection Following Open Wedge High Tibial Osteotomy for Varus Knee Osteoarthritis: A Retrospective Cohort Study.

Background: As the worldwide population ages, the population receiving open wedge high tibial osteotomy (OWHTO) is growing, and surgical site infection (SSI) is a rare but fatal surgical complication. This study aimed to identify risk factors independently associated with SSI following OWHTO and develop a predictive nomogram. Methods: Clinical data of patients who received OWHTO and followed up for more than 12 months in our hospital were retrospectively reviewed. Multivariable logistic regression was performed to determine independent risk factors for SSI and to construct predictive nomograms. The study further illustrated the predictive performance of the model by using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: A total of 1294 eligible patients were included in the study. Multivariate analysis revealed tobacco consumption (OR=3.44, p=0.010), osteotomy size ≥12 mm (OR=3.3, p=0.015), the use of allogeneic bone or artificial bone graft substitutes (allogeneic bone vs none, OR=4.08, p=0.037; artificial bone vs none, OR=5.16, p=0.047), Kellgren-Lawrence (K-L) grade IV (OR=2.5, p=0.046), systemic immune-inflammation index (SII) >423.62 (OR=6.2, p<0.001), high-sensitivity C-reactive protein (HCRP) >2.6 mg/L (OR=2.42, p=0.044), and a higher level of fasting blood glucose (FBG) (OR=1.32, p=0.022) were the independent predictors of SSI. The cutoff score of the model was 148, with a sensitivity of 76.0% and specificity of 81.0%. The concordance index (C-index) and Brier score of the nomogram were 0.856 and 0.017, and the corrected values after 1000 bootstrapping validations were 0.820 and 0.018, respectively. Furthermore, the ROC curve, calibration curve, and DCA exhibited excellent predictive accuracy and clinical applicability of the model. Conclusion: This study developed a dynamic nomogram based on seven predictors, which allowed surgeons to individualize risk stratification of patients and intervene promptly to reduce SSI rates.

Barriers to clinical nurse participation in the internet-based home visiting program: a qualitative study.

BACKGROUND: Home visits are an important part of home care. With increasing demand and the rapid development of information technology, an increasing number of regions are experimenting with the use of information technology in home visits, hoping to meet the needs of more patients through technological interventions. However, most of the current studies have focused on patient health improvement through home visits, neglecting to consider the actual experience of nurses as service providers in participating in Internet-based programs. Thus, the purpose of this research is to explore what is holding nurses back from participating after the Internet has been added to traditional home visiting programs. METHODS: This research was designed with an exploratory-descriptive qualitative analysis method. Semistructured interviews were used to collect information on barriers to nurses' participation in the Internet-based home visiting program. Participants included 16 clinical nurses working in various hospitals in Nanjing, China. The thematic analysis method was used to analyze the information. RESULTS: This research identified three themes and twelve subthemes that hinder clinical nurse engagement in the Internet-based home visiting program. The three themes included multiple barriers to individuals, different service modes, and emerging organizational problems. CONCLUSIONS: As a new form of traditional home visiting program in information society, Internet-based home visiting has many shortcomings in the overall program design and service management specifications. For more patients living at home to receive quality care services, it is necessary to take more effective measures to encourage nurses' participation at three levels: nurse demand, service process, and organizational management.