Asiaticoside inhibits renal fibrosis development by regulating the miR-142-5p/ACTN4 axis.

Renal fibrosis results in the progressive renal dysfunction and leads to chronic kidney disease (CKD) and ultimately end-stage renal disease. Asiaticoside was reported to regulate synaptopodin, desmin, nephrin, and podocin levels in adriamycin-induced nephropathy of rats. In this study, we found out that asiaticoside inhibited renal fibrosis in vitro and in vivo. Additionally, miR-142-5p was upregulated in in vitro and in vivo models of CKD. MiR-142-5p promoted the levels of collagen-I, collagen-IV, and fibronectin proteins. Additionally, miR-142-5p overexpression partly rescued the protective effect of asiaticoside on renal fibrosis. Mechanistically, miR-142-5p inhibited ACTN4 levels by binding with its 3´untranslated region, and further reduced its translation. Treatment of asiaticoside decreased miR-142-5p levels and increased ACTN4 levels. Rescue assays revealed that ACTN4 overexpression partially rescued the effect of miR-142-5p on renal fibrosis. Asiaticoside mitigated renal fibrosis by regulating the miR-142-5p/ACTN4 axis. In conclusion, asiaticoside inhibits renal fibrosis by regulating the miR-142-5p/ACTN4 axis. This novel discovery suggested that asiaticoside may serve as a potential medicine for renal fibrosis improvement.

A nomogram for predicting overall survival in patients with Ewing sarcoma: a SEER-based study.

BACKGROUND: Ewing sarcoma, the second most frequent bone tumor in children and adolescents, is often presented with localized disease or metastatic-related symptoms. In this study, we aim to construct and validate a nomogram for patients with Ewing sarcoma to predict the 3- and 5-year overall survival (OS) based on the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Demographic and clinic pathological characteristics of patients with Ewing sarcoma diagnosed between 2010 and 2015 were extracted from SEER database. Univariate and multivariate Cox analyses were carried out to identify the independent characteristics. The independent factors were further included into the construction of a nomogram. Finally, c-index and calibration curves were used to validate the nomogram. RESULTS: A total of 578 patients were enrolled into our analysis. The results of univariate Cox analysis showed that age, 7th AJCC stage, 7th AJCC T stage, 7th AJCC N stage, 7th AJCC M stage, metastatic status to lung, liver and bone were significant factors. Multivariate Cox analysis was performed and it confirmed age, N stage and bone metastasis as independent variables. Next, a nomogram was constructed using these independent variables in prediction to the 3- and 5-year OS. Furthermore, favorable results with c-indexes (0.757 in training set and 0.697 in validation set) and calibration curves closer to ideal curves indicated the accurate predictive ability of this nomogram. CONCLUSIONS: The individualized nomogram demonstrated a good ability in prognostic prediction for patients with Ewing sarcoma.

An Anisotropic Hydrogel Based on Mussel-Inspired Conductive Ferrofluid Composed of Electromagnetic Nanohybrids.

Anisotropic hydrogels with a hierarchical structure can mimic biological tissues, such as neurons or muscles that show directional functions, which are important factors for signal transduction and cell guidance. Here, we report a mussel-inspired approach to fabricate an anisotropic hydrogel based on a conductive ferrofluid. First, polydopamine (PDA) was used to mediate the formation of PDA-chelated carbon nanotube-Fe3O4 (PFeCNT) nanohybrids and also used as a dispersion medium to stabilize the nanohybrids to form a conductive ferrofluid. The ferrofluid can respond to an orientated magnetic field and be programed to form aligned structures, which were then frozen in a hydrogel network formed via in situ free-radical polymerization and gelation. The resulted hydrogel shows directional conductive and mechanical properties, mimicking an oriented biological tissue. Under external electrical stimulation, the orientated PFeCNT nanohybrids can be sensed by the myoblasts cultured on the hydrogel, resulting in the oriented growth of cells. In summary, the mussel-inspired anisotropic hydrogel with its aligned structural complexity and anisotropic properties together with the cell affinity and tissue adhesiveness is a potent multifunctional biomaterial for mimicking oriented tissues to guide cell proliferation and tissue regeneration.

Male density, a signal for population self-regulation in Alligator sinensis.

The regulation of population density is suggested to be indirect and occurs with a time-lag effect, as well as being female centred. Herein, we present a quantitative analysis on the precise, timely and male-dominated self-regulation of Chinese alligator ( Alligator sinensis) populations. Analysis of 31 years of data revealed gender differences in regulation patterns. Population dynamics were restricted by male density rather than population density, and population growth was halted (birth rate = 0) when male density exceeded 83.14 individuals per hectare, until some males were removed, especially adult males. This rapid and accurate response supports the notions of intrinsic mechanisms and population-wide regulation response. Furthermore, density stress affected mating success rather than parental care to juveniles, i.e. females avoided unnecessary reproduction costs, which may represent an evolutionary advantage. Our findings highlighted the importance of further studies on related physiological mechanisms that focus on four characteristics: quantity breeds quality, gender differences, male density thresholds and nonlinearity.

A Fine-Grained User-Divided Privacy-Preserving Access Control Protocol in Smart Watch.

A smart watch is a kind of emerging wearable device in the Internet of Things. The security and privacy problems are the main obstacles that hinder the wide deployment of smart watches. Existing security mechanisms do not achieve a balance between the privacy-preserving and data access control. In this paper, we propose a fine-grained privacy-preserving access control architecture for smart watches (FPAS). In FPAS, we leverage the identity-based authentication scheme to protect the devices from malicious connection and policy-based access control for data privacy preservation. The core policy of FPAS is two-fold: (1) utilizing a homomorphic and re-encrypted scheme to ensure that the ciphertext information can be correctly calculated; (2) dividing the data requester by different attributes to avoid unauthorized access. We present a concrete scheme based on the above prototype and analyze the security of the FPAS. The performance and evaluation demonstrate that the FPAS scheme is efficient, practical, and extensible.

Tell the Device Password: Smart Device Wi-Fi Connection Based on Audio Waves.

IoT devices are now enriching people's life. However, the security of IoT devices seldom attracts manufacturers' attention. There are already some solutions to the problem of connecting a smart device to a user's wireless network based on the 802.11 transmission such as Smart Config from TI. However, it is insecure in many situations, and it does not have a satisfactory transmission speed, which does not mean that it has a low bit rate. It usually takes a long time for the device to recognize the data it receives and decode them. In this paper, we propose a new Wi-Fi connection method based on audio waves. This method is based on MFSK (Multiple frequency-shift keying) and works well in short distance, which enables the correctness and efficiency. In addition, audio waves can hardly be eavesdropped, which provides higher security than other methods. We also put forward an encryption solution by using jamming signal, which can greatly improve the security of the transmission.

Y-DWMS: A Digital Watermark Management System Based on Smart Contracts.

With the development of information technology, films, music, and other publications are inclined to be distributed in digitalized form. However, the low cost of data replication and dissemination leads to digital rights problems and brings huge economic losses. Up to now, existing digital rights management (DRM) schemes have been powerless to deter attempts of infringing digital rights and recover losses of copyright holders. This paper presents a YODA-based digital watermark management system (Y-DWMS), adopting non-repudiation of smart contract and blockchain, to implement a DRM mechanism to infinitely amplify the cost of infringement and recover losses copyright holders suffered once the infringement is reported. We adopt game analysis to prove that in Y-DWMS, the decision of non-infringement always dominates rational users, so as to fundamentally eradicate the infringement of digital rights, which current mainstream DRM schemes cannot reach.

Heparinized Polyurethane Surface Via a One-Step Photografting Method.

Traditional methods using coupling chemistry for surface grafting of heparin onto polyurethane (PU) are disadvantageous due to their generally low efficiency. In order to overcome this problem, a quick one-step photografting method is proposed here. Three heparin derivatives incorporating 0.21, 0.58, and 0.88 wt% pendant aryl azide groups were immobilized onto PU surfaces, leading to similar grafting densities of 1.07, 1.17, and 1.13 µg/cm², respectively, yet with increasing densities of anchoring points. The most negatively charged surface and the maximum binding ability towards antithrombin III were found for the heparinized PU with the lowest amount of aryl azide/anchor sites. Furthermore, decreasing the density of anchoring points was found to inhibit platelet adhesion to a larger extent and to prolong plasma recalcification time, prothrombin time, thrombin time, and activated partial thromboplastin time to a larger extent. This was also found to enhance the bioactivity of immobilized heparin from 22.9% for raw heparin to 36.9%. This could be explained by the enhanced molecular mobility of immobilized heparin when it is more loosely anchored to the PU surface, as well as a higher surface charge.

On channel estimation schemes for APD-based DDM-OFDM-PONs under sub-Nyquist sampling.

Implementing preprocessing in a delay-division multiplexing (DDM) orthogonal frequency-division multiplexing (OFDM) passive optical network (PON) requires a priori knowledge of channel responses, which need to be estimated under the constraint of sub-Nyquist analog-to-digital sampling. The localized approach allocates subcarriers in different frequency zones to training symbols in different time slots for channel estimation without spectral overlap. Unfortunately, the localized scheme is susceptible to inaccurate estimation when using an avalanche photodiode (APD), due to variations in APD saturation associated with different training symbols. Instead of localizing all subcarriers of a training symbol in a single frequency zone, we propose distributing training subcarriers through various frequency zones. This distributed scheme would prevent spectral overlap and also reduce the degree of variation in APD saturation, thereby improving the accuracy of channel estimation. Alternatively, we propose an orthogonal scheme in which each training symbol uses all of the subcarriers simultaneously. The orthogonality specified among consecutive training symbols should make it possible to estimate the channel response with low computational complexity. We conducted experiments to compare various schemes used for channel estimation in a 25-Gbps APD-based OFDM-PON. Our results revealed that the orthogonal scheme achieved the best results, and the localized scheme provided the worst channel estimates. We demonstrate the application of the orthogonal scheme in a penalty-free DDM system at 1/32 of the Nyquist rate, which provided a loss budget of 28 dB after fiber transmission over a distance of 25 km.

A Mussel-Inspired Conductive, Self-Adhesive, and Self-Healable Tough Hydrogel as Cell Stimulators and Implantable Bioelectronics.

A graphene oxide conductive hydrogel is reported that simultaneously possesses high toughness, self-healability, and self-adhesiveness. Inspired by the adhesion behaviors of mussels, our conductive hydrogel shows self-adhesiveness on various surfaces and soft tissues. The hydrogel can be used as self-adhesive bioelectronics, such as electrical stimulators to regulate cell activity and implantable electrodes for recording in vivo signals.

Demonstration of end-to-end cloud-DSL with a PON-based fronthaul supporting 5.76-Gb/s throughput with 48 eCDMA-encoded 1024-QAM discrete multi-tone signals.

We experimentally demonstrate an end-to-end ultra-broadband cloud-DSL network using passive optical network (PON) based fronthaul with electronic code-division-multiple-access (eCDMA) encoding and decoding. Forty-eight signals that are compliant with the very-high-bit-rate digital subscriber line 2 (VDSL2) standard are transmitted with a record throughput of 5.76 Gb/s over a hybrid link consisting of a 20-km standard single-mode fiber and a 100-m twisted pair.

Can Multimodal Analgesia Reduce Postoperative Opioid Consumption in Patients Undergoing Shoulder Arthroscopy? A Retrospective Study.

AIM: The aim of this study was to investigate whether multimodal analgesia can decrease postoperative opioid usage in patients undergoing shoulder arthroscopy. METHODS: Patients diagnosed with subacromial impingement syndrome who underwent acromioplasty at our institution between October 2022 and November 2023 were retrospectively analyzed. Patients were divided into an observation group and a control group based on postoperative pain management methods. The control group received intravenous self-controlled electronic analgesia (sufentanil injection 1 µg/kg + butorphanol injection 4 mg + 0.9% NaCl injection to 100 mL), while the observation group received multimodal analgesia (ropivacaine subacromial pump 3 mL/h, combined with oral celecoxib and acetaminophen). Visual Analog Scale (VAS) scores were recorded preoperatively and at various postoperative time points, and opioid usage, length of hospital stay, and analgesia-related complications within 1 week postoperatively were compared between groups. The 36-item Short Form Health Survey (SF-36) scores and the Constant-Murley score (CMS), were also assessed 1 day and 1 week after treatment. RESULTS: One hundred thirty-two patients were included in the study, 66 in the observation group and 66 in the control group. In the control group, there were 46 males and 20 females, with a mean age of 55.47 ± 11.42 years and in the observation group 44 males and 22 females, with a mean age of 56.13 ± 12.19 years The observation group consistently reported significantly lower pain intensity compared to the control group at 8 h (T1), 24 (T2), and 48 h (T3) after surgery (p < 0.05). Additionally, the observation group exhibited significantly lower opioid usage and complication rates compared to the control group (p < 0.05). SF-36 scores and CMS scores were significantly higher in the observation group 1 week after treatment compared to the control group (p < 0.05). CONCLUSIONS: Following shoulder arthroscopy, multimodal analgesia effectively reduces opioid consumption, lowers complication rates, and provides effective short-term pain relief. This approach carries significant implications for improving patient outcomes.

Wearable Magnetoelectric Stimulation for Chronic Wound Healing by Electrospun CoFe2O4@CTAB/PVDF Dressings.

Magnetoelectric stimulation is a promising therapy for various disorders due to its high efficacy and safety. To explore its potential in chronic skin wound treatment, we developed a magnetoelectric dressing, CFO@CTAB/PVDF (CCP), by electrospinning cetyltrimethylammonium bromide-modified CoFe2O4 (CFO) particles with polyvinylidene fluoride. Cetyltrimethylammonium bromide (CTAB) serves as a dispersion surfactant for CFO, with its quaternary ammonium cations imparting antibacterial and hydrophilic properties to the dressing. Electrospinning polarizes polyvinylidene fluoride (PVDF) molecules and forms a fibrous membrane with flexibility and breathability. With a wearable electromagnetic induction device, a dynamic magnetic field is established to induce magnetostrictive deformation of CFO nanoparticles. Consequently, a piezoelectric potential is generated on the surface of PVDF nanofibers to enhance the endogenous electrical field in the wound, achieving a cascade coupling of electric-magnetic-mechanical-electric effects. Bacteria and cell cultures show that 2% CTAB effectively balances antibacterial property and fibroblast activity. Under dynamic magnetoelectric stimulation, the CCP dressing demonstrates significant upregulation of TGF-ß, FGF, and VEGF, promoting L929 cell adhesion and proliferation. Moreover, it facilitates the healing of diabetic rat skin wounds infected with Staphylococcus aureus within 2 weeks. Histological and molecular biology evaluations confirm the anti-inflammatory effect of CTAB and the accelerated formation of collagen and vessel by electrical stimulation. This work provides insights into the application of magnetoelectric stimulation in the healing of chronic wounds.

Natural Polysaccharide Film-Based Triboelectric Sensor for Fruit Transportation Collision Monitoring.

Transportation-induced damage to fresh produce is a big challenge in logistics. Current acceleration and pressure sensors for collision monitoring face issues of power dependency, high cost, and environmental concerns. Here, a self-powered and environmentally friendly triboelectric sensor has been developed to monitor fruit collisions in transportation packaging. Microcrystalline cellulose/chitosan and sodium alginate films were prepared as positive and negative tribo-layers to assemble a natural polysaccharide film-based triboelectric nanogenerator (NP-TENG). The NP-TENG's electrical output was proportional to the structure parameters (contact surface roughness and separation gap of the tribo-layers) and the vibration factors (force and frequency) and exhibited excellent stability and durability (over 100,000 cycles under 13 N at 10 Hz). The high mechanical-to-electrical conversion efficiency (instantaneous areal power density of 9.6 mW/m2) and force sensitivity (2.2 V/N) enabled the NP-TENG to be a potential sensor for monitoring fresh produce collisions in packaging during logistics. Transportation simulation measurements of kiwifruits verified that the sensor's electrical outputs increased with the vibration frequency and stacking layer while varying at different packaging locations. This study suggests that the NP-TENG can effectively monitor collision damage during fruit transportation, providing new insights into developing intelligent food packaging systems to reduce postharvest supply chain losses.

Growing attention on the toxicity of Chinese herbal medicine: a bibliometric analysis from 2013 to 2022.

Introduction: Despite the clinical value of Chinese herbal medicine (CHM), restricted comprehension of its toxicity limits the secure and efficacious application. Previous studies primarily focused on exploring specific toxicities within CHM, without providing an overview of CHM's toxicity. The absence of a quantitative assessment of focal points renders the future research trajectory ambiguous. Therefore, this study aimed to reveal research trends and areas of concern for the past decade. Methods: A cross-sectional study was conducted on publications related to CHM and toxicity over the past decade from Web of Science Core Collection database. The characteristics of the publication included publication year, journal, institution, funding, keywords, and citation counts were recorded. Co-occurrence analysis and trend topic analysis based on bibliometric analysis were conducted on keywords and citations. Results: A total of 3,225 publications were analyzed. Number of annal publications increased over the years, with the highest number observed in 2022 (n = 475). The Journal of Ethnopharmacology published the most publications (n = 425). The most frequently used toxicity classifications in keywords were hepatotoxicity (n = 119) or drug-induced liver injury (n = 48), and nephrotoxicity (n = 40). Co-occurrence analysis revealed relatively loose connections between CHM and toxicity, and their derivatives. Keywords emerging from trend topic analysis for the past 3 years (2019-2022) included ferroptosis, NLRP3 inflammasome, machine learning, network pharmacology, traditional uses, and pharmacology. Conclusion: Concerns about the toxicity of CHM have increased in the past decade. However, there remains insufficient studies that directly explore the intersection of CHM and toxicity. Hepatotoxicity and nephrotoxicity, as the most concerned toxicity classifications associated with CHM, warrant more in-depth investigations. Apoptosis was the most concerned toxicological mechanism. As a recent increase in attention, exploring the mechanisms of ferroptosis in nephrotoxicity and NLRP3 inflammasome in hepatotoxicity could provide valuable insights. Machine learning and network pharmacology are potential methods for future studies.

[Efficacy evaluation of treating cervical spondylopathy with the Discover artificial cervical disc prosthesis].

OBJECTIVE: To explore the clinical and radiological outcomes of Discover artificial cervical disc arthroplasty and the range of motion status on adjacent segments for cervical spondylosis causing radiculopathy or myelopathy. METHODS: A total of 18 consecutive patients underwent cervical arthroplasty with the Discover artificial cervical disc at our hospital. Clinical and radiological follow-ups were conducted. Their radiographic parameters of treatment and adjacent segments were evaluated at Month 1, 3, 6, 12, 18 post-operation. And the Japanese Orthopedic Association (JOA) score, visual analog scale (VAS) pain score and Odom's scale were recorded and analyzed. RESULTS: During follow-ups over an average of 15 months, there was no occurrence of vascular injury, severe complications or prosthesis displacement and loosening. The score of JOA was 7.2±1.8 at preoperation and 16.7±4.5 at postoperation. And the score of VAS was 8.15±1.65 at preoperation and 2.03±1.12 at postoperation. CONCLUSION: Discover artificial cervical disc arthroplasty is efficacious and the patients recover quickly. Targeted cervical segments may be stabilized and their physiological ranges of motion preserved.

IDRM: Brain tumor image segmentation with boosted RIME optimization.

Timely diagnosis of medical conditions can significantly mitigate the risks they pose to human life. Consequently, there is an urgent demand for an effective auxiliary model that assists physicians in accurately diagnosing medical conditions based on imaging data. While multi-threshold image segmentation models have garnered considerable attention due to their simplicity and ease of implementation, the selection of threshold combinations greatly influences the segmentation performance. Traditional optimization algorithms often require substantial time to address multi-threshold image segmentation problems, and their segmentation accuracy is frequently unsatisfactory. As a result, metaheuristic algorithms have been employed in this domain. However, several algorithms suffer from drawbacks such as premature convergence and inadequate exploration of the solution space when it comes to threshold selection. For instance, the recently proposed optimization algorithm RIME, inspired by the physical phenomenon of rime-ice, falls short in terms of avoiding local optima and fully exploring the solution space. Therefore, this study introduces an enhanced version of RIME, called IDRM, which incorporates an interactive mechanism and Gaussian diffusion strategy. The interactive mechanism facilitates information exchange among agents, enabling them to evolve towards more promising directions and increasing the likelihood of discovering the optimal solution. Additionally, the Gaussian diffusion strategy enhances the agents' local exploration capabilities and expands their search within the solution space, effectively preventing them from becoming trapped in local optima. Experimental results on 30 benchmark test functions demonstrate that IDRM exhibits favorable optimization performance across various optimization functions, showcasing its robustness and convergence properties. Furthermore, the algorithm is applied to select threshold combinations for brain tumor image segmentation, and the results are evaluated using metrics such as Peak Signal-to-Noise Ratio (PSNR) and Structural Similarity Index Measure (SSIM). The overall findings consistently highlight the exceptional performance of this approach, further validating the effectiveness of IDRM in addressing image segmentation problems.

Flexible, Breathable, and Self-Powered Patch Assembled of Electrospun Polymer Triboelectric Layers and Polypyrrole-Coated Electrode for Infected Chronic Wound Healing.

Chronic wound healing is often impaired by bacterial infection and weak trans-epithelial potential. Patches with electrical stimulation and bactericidal activity may solve this problem. However, inconvenient power and resistant antibiotics limit their application. Here, we proposed a self-powered and intrinsic bactericidal patch based on a triboelectric nanogenerator (TENG). Electrospun polymer tribo-layers and a chemical vapor-deposited polypyrrole electrode are assembled as the TENG, offering the patch excellent flexibility, breathability, and wettability. Electrical stimulations by harvesting mechanical motions and positive charges on the polypyrrole surface kill over 96% of bacteria due to their synergistic effects on cell membrane disruption. Moreover, the TENG patch promotes infected diabetic rat skin wounds to heal within 2 weeks. Cell culture and animal tests suggest that electrical stimulation enhances gene expression of growth factors for accelerated wound healing. This work provides new insights into the design of wearable and multifunctional electrotherapy devices for chronic wound treatment.

Sequential Anti-Infection and Proangiogenesis of DMOG@ZIF-8/Gelatin-PCL Electrospinning Dressing for Chronic Wound Healing.

Bacterial infection and insufficient neovascularization are two major obstacles to the healing of chronic wounds. Here, we present an antibacterial and proangiogenic dressing by encapsulating dimethyloxalylglycine (DMOG) in zeolitic imidazolate framework-8 (ZIF-8) and electrospinning it with gelatin-polycaprolactone (Gel-PCL). As Gel-PCL nanofibers degrade, ZIF-8 nanoparticles decompose, sequentially releasing bactericidal zinc ions and angiogenic DMOG molecules. This cascade process matches the wound-healing stages, ensuring suitable bioavailability and an effective duration of the active components while minimizing their side effects. In vitro, zinc ions released from the dressing (2.5% DMOG@ZIF-8) can eliminate over 90% of Escherichia coli and Staphylococcus aureus without compromising fibroblast cell proliferation and adhesion. In vivo, the dressing can heal skin wounds in Staphylococcus aureus-infected diabetic rats within 2 weeks, facilitated by the DMOG molecules discharged from ZIF-8 (loading rate 21.3%). Immunohistochemical analysis confirmed the regulated expression of factors by zinc ions and DMOG molecules. This work provides new insights into the design of multifunctional dressings for the treatment of chronic wounds.

MDM2 inhibitor Nutlin-3a suppresses proliferation and promotes apoptosis in osteosarcoma cells.

Restoring p53 activity by inhibiting the interaction between p53 and the mouse double minutes clone 2 (MDM2) offers an attractive approach to cancer therapy. Nutlin-3a is a small-molecule inhibitor that inhibits MDM2 binding to p53 and subsequent p53-dependent DNA damage signaling. In this study, we determined the efficacy of Nutlin-3a in inducing p53-mediated cell death in osteosarcoma (OS) cell lines both in vivo and in vitro. Targeted disruption of the p53-MDM2 interaction by Nutlin-3a stabilizes p53 and selectively activates the p53 pathway only in OS cells with wild-type p53, resulting in a pronounced anti-proliferative and cytotoxic effect due to G1 cell cycle arrest and apoptosis both in vitro and in vivo. p53 dependence of these alternative outcomes of Nutlin-3a treatment was shown by the abrogation of these effects when p53 was knocked-down by small interfering RNA. These data suggest that the disruption of p53-MDM2 interaction by Nutlin-3a might be beneficial for OS patients with MDM2 amplification and wt p53 status.