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.

The incidence and risk factors of perioperative recurrent stroke in elderly patients with previous ischemic stroke receiving hip fracture surgery.

BACKGROUND: Data are currently lacking regarding perioperative stroke recurrence in hip fracture patients with previous stroke. We aimed to analyze the incidence and risk factors of perioperative stroke recurrence in elderly patients with previous stroke who underwent hip fracture surgery. METHODS: We used 2019 and 2020 data from the United States National Inpatient Sample database. We identified elderly patients with previous ischemic stroke who had undergone hip fracture surgery to analyze the incidence of stroke recurrence. A 1:4 propensity score matching was used to balance confounding factors related to demographic data and matched the control group with the stroke recurrence group. Risk factors for stroke recurrence were determined using univariate and multivariate logistic analysis. RESULTS: The incidence of perioperative stroke recurrence in elderly patients with previous stroke who underwent hip fracture surgery was 5.7% (51/882). Multivariate logistic regression analysis showed that intertrochanteric fracture (odds ratio 2.24, 95% confidence interval 1.14-4.57; p = 0.021), hypertension (odds ratio 2.49, 95% confidence interval 1.26-5.02; p = 0.009), and postoperative pneumonia (odds ratio 4.35, 95% confidence interval 1.59-11.82; p = 0.004) were independently associated with stroke recurrence. CONCLUSIONS: The perioperative stroke recurrence rate in elderly hip fracture patients with previous stroke was 5.7%. Intertrochanteric fracture, hypertension, and postoperative pneumonia were identified as factors significantly associated with stroke recurrence in this study. Adequate systemic support post-fracture, effective blood pressure management, and proactive infection prevention may help reduce stroke recurrence, especially in patients with intertrochanteric fractures.

Developments and applications of the OPTIMADE API for materials discovery, design, and data exchange.

The Open Databases Integration for Materials Design (OPTIMADE) application programming interface (API) empowers users with holistic access to a growing federation of databases, enhancing the accessibility and discoverability of materials and chemical data. Since the first release of the OPTIMADE specification (v1.0), the API has undergone significant development, leading to the v1.2 release, and has underpinned multiple scientific studies. In this work, we highlight the latest features of the API format, accompanying software tools, and provide an update on the implementation of OPTIMADE in contributing materials databases. We end by providing several use cases that demonstrate the utility of the OPTIMADE API in materials research that continue to drive its ongoing development.

Spatiotemporal transcriptome atlas reveals gene regulatory patterns during the organogenesis of the rapid growing bamboo shoots.

Bamboo with its remarkable growth rate and economic significance, offers an ideal system to investigate the molecular basis of organogenesis in rapidly growing plants, particular in monocots, where gene regulatory networks governing the maintenance and differentiation of shoot apical and intercalary meristems remain a subject of controversy. We employed both spatial and single-nucleus transcriptome sequencing on 10× platform to precisely dissect the gene functions in various tissues and early developmental stages of bamboo shoots. Our comprehensive analysis reveals distinct cell trajectories during shoot development, uncovering critical genes and pathways involved in procambium differentiation, intercalary meristem formation, and vascular tissue development. Spatial and temporal expression patterns of key regulatory genes, particularly those related to hormone signaling and lipid metabolism, strongly support the hypothesis that intercalary meristem origin from surrounded parenchyma cells. Specific gene expressions in intercalary meristem exhibit regular and dispersed distribution pattern, offering clues for understanding the intricate molecular mechanisms that drive the rapid growth of bamboo shoots. The single-nucleus and spatial transcriptome analysis reveal a comprehensive landscape of gene activity, enhancing the understanding of the molecular architecture of organogenesis and providing valuable resources for future genomic and genetic studies relying on identities of specific cell types.

Fabrication of liquid-free ionic conductive elastomer (ICE) from cellulose-rosin derived poly(esterimide) towards temperature-tolerant and solvent-resistant UV shadowless adhesive and sensor.

Recently, the utilization of the cellulose to fabricate the multifunctional materials with aim to replace the petroleum-based product, is receiving significant attentions. However, the development of cellulose-based multifunctional materials with high mechanical strength and temperature resistance is still a challenge. Herein, the intrinsic feature and property of cellulose and rosin were creatively employed to fabricate a novel cellulose-rosin based poly(esterimide) (PEI) by esterification reaction and imidization reaction, and the obtained cellulose-rosin derived PEI exhibits superior thermal stability. Then the as-prepared cellulose-rosin derived PEI was dissolved in polymerizable deep eutectic solvents (PDES) and in-situ formed the ionic conductive elastomer (ICE) with via UV-induced polymerization. These cellulose-rosin based ICE exhibited excellent mechanical properties, solvent resistance, and temperature tolerance. By adjusting the mass ratio of cellulose-rosin derived PEI and PDES, the as-prepared liquid-free ICE functions as UV shadowless adhesive and wearable sensors. The bonding strength of UV shadowless adhesive could 1.52 MPa, which could be applied to fix the broken glass toy models. Furthermore, wearable sensors based those ICE could monitor the large and subtle movements even under extreme environmental condition, such as being soaked in organic solvent (such as tetrahydrofuran) or at low/high temperature (-25 °C or 80 °C). This work opens a new avenue for the next-generation of multifunctional ICE.

Activating Biocake Communities Retards Jumps of Transmembrane Pressure in Membrane Bioreactors.

Sudden jump of transmembrane pressure (TMP) in membrane bioreactors (MBRs), associated with abrupt aggravation of membrane fouling, limits practical applications of MBRs and calls for effective mitigation strategies. While the TMP jump is generally related to the bacterial activity of biocakes, the mechanisms underlying the TMP jump remain unclear. Herein, we conducted various backwash protocols with different nutrient (e.g., nitrate and sodium acetate) loadings on fouled membranes in MBRs to reveal the critical role of bacterial activity of biocakes for the TMP jump. The filtration tests showed a lower TMP jump rate for the membrane backwashed with a nutrient solution (a mixture of 180 mg/L NaNO3 and 200 mg/L NaAc, averaged at 1.40 kPa/d) than that backwashed with tap water (averaged at 3.56 kPa/d), implying that TMP jump could be efficiently mitigated by providing sufficient nutrients to biocake bacteria. The characterization of biocakes showed that high-nutrient solution backwash considerably increased bacterial viability and activity, while considerably reducing biomolecule accumulation on membranes. The keystone taxa (e.g., g_Aeromonas and o_Chitinophagaceae) in the network of nutrient-enriched biocake communities were involved in nitrate reduction and biomolecule degradation. Ecological null model analyses revealed that the deterministic manner mainly shaped biocake communities with high-nutrient availability. Overall, this study highlights the significance of the bacterial activity of biocakes for TMP development and provides potential alternatives for controlling membrane fouling.

Pyrrolopyrrole Cyanine J-Aggregate Nanoparticles with High Near-Infrared Fluorescence Brightness and Photothermal Performance for Efficient Phototheranostics.

Advanced photosensitizers for high-performance fluorescence imaging-guided photothermal therapy demand excellent near-infrared (NIR) brightness [molar absorption coefficient (ε) × quantum yield (QY)] and exceptional photothermal performance [ε × photothermal conversion efficiency (PCE)]. However, integrating high brightness and potent photothermal performance within a single molecule faces a formidable challenge. This article proposes a method to address this issue by preparing J-aggregate nanoparticles (NPs) using molecules with high ε. J-aggregates effectively improve QY and induce molecular emission redshift, while high ε molecules play a crucial role in improving the brightness and photothermal performance. By optimizing the molecular structure based on the pyrrolopyrrole cyanine (PPCy), precise control over the QY and PCE of PPCy J-aggregates is achieved. Ultimately, PDDO NPs exhibiting superior brightness (ε × QY = 3.32 × 104 M-1 cm-1) and photothermal performance (ε × PCE = 1.21 × 105 M-1 cm-1) are identified as high-performance photosensitizers. Notably, each parameter represents one of the highest levels among the reported fluorescence or photothermal probes to date. The in vivo studies demonstrate that PDDO NPs possess exceptional NIR imaging capabilities and remarkable photothermal tumor inhibition rates. This study provides innovative insights into the development of high-performance multifunctional photosensitizers.

CircHIPK2 Contributes Cell Growth in Intestinal Epithelial of Colitis and Colorectal Cancer through Promoting TAZ Translation.

Colorectal cancer (CRC) and inflammatory bowel disease (IBD) are escalating global health concerns. Despite their distinct clinical presentations, both disorders share intricate genetic and molecular interactions. The Hippo signaling pathway plays a crucial role in regulating cell processes and is implicated in the pathogenesis of IBD and CRC. Circular RNAs (circRNAs) have gained attention for their roles in various diseases, including IBD and CRC. However, a comprehensive understanding of specific circRNAs involved in both IBD and CRC, and their functional roles is lacking. Here, it is found that circHIPK2 (hsa_circRNA_104507) is a bona fide circRNA consistently upregulated in both IBD and CRC suggesting its potential as a biomarker. Furthermore, silencing of circHIPK2 suppressed the growth of CRC cells in vitro and in vivo. Interestingly, decreased circHipk2 potentiated dextran sulfate sodium (DSS)-induced colitis but alleviated colitis-associated tumorigenesis. Most significantly, mechanistic investigations further unveil that circHIPK2, mediated by FUS, interacting with EIF4A3 to promote the translation of TAZ, ultimately increasing the transcription of downstream target genes CCN1 and CCN2. Taken together, circHIPK2 emerges as a key player in the shared mechanisms of IBD and CRC, modulating the Hippo signaling pathway. CircHIPK2-EIF4A3 axis contributes to cell growth in intestinal epithelial of colitis and CRC by enhancing TAZ translation.

Computational Polarization Imaging In Vivo through Surgical Smoke Using Refined Polarization Difference.

In surgery, the surgical smoke generated during tissue dissection and hemostasis can degrade the image quality, affecting tissue visibility and interfering with the further image processing. Developing reliable and interpretable computational imaging methods for restoring smoke-affected surgical images is crucial, as typical image restoration methods relying on color-texture information are insufficient. Here a computational polarization imaging method through surgical smoke is demonstrated, including a refined polarization difference estimation based on the discrete electric field direction, and a corresponding prior-based estimation method, for better parameter estimation and image restoration performance. Results and analyses for ex vivo, the first in vivo animal experiments, and human oral cavity tests show that the proposed method achieves visibility restoration and color recovery of higher quality, and exhibits good generalization across diverse imaging scenarios with interpretability. The method is expected to enhance the precision, safety, and efficiency of advanced image-guided and robotic surgery.

A Mendelian randomization study of the entire phenome to explore the causal links between epilepsy.

OBJECTIVE: The causes and triggering factors of epilepsy are still unknown. The results of genome-wide association studies can be utilized for a phenome-wide association study using Mendelian randomization (MR) to identify potential risk factors for epilepsy. METHODS: This study utilizes two-sample MR analysis to investigate whether 316 phenotypes, including lifestyle, environmental factors, blood biomarker, and more, are causally associated with the occurrence of epilepsy. The primary analysis employed the inverse variance weighted (IVW) model, while complementary MR analysis methods (MR Egger, Wald ratio) were also employed. Sensitivity analyses were also conducted to evaluate heterogeneity and pleiotropy. RESULTS: There was no evidence of a statistically significant causal association between the examined phenotypes and epilepsy following Bonferroni correction (p < 1.58 × 10-4) or false discovery rate correction. The results of the MR analysis indicate that the frequency of tiredness or lethargy in the last 2 weeks (p = 0.042), blood uridine (p = 0.003), blood propionylcarnitine (p = 0.041), and free cholesterol (p = 0.044) are suggestive causal risks for epilepsy. Lifestyle choices, such as sleep duration and alcohol consumption, as well as biomarkers including steroid hormone levels, hippocampal volume, and amygdala volume were not identified as causal factors for developing epilepsy (p > 0.05). CONCLUSIONS: Our study provides additional insights into the underlying causes of epilepsy, which will serve as evidence for the prevention and control of epilepsy. The associations observed in epidemiological studies may be partially attributed to shared biological factors or lifestyle confounders.

Design, synthesis and biological evaluation of indoline-maleimide conjugates as potential antitumor agents for the treatment of colorectal cancer.

An efficient protocol for direct coupling of maleimides and indolines at the C7-position was achieved under Rh(III) catalysis. Thirty four novel indoline-maleimide conjugates were prepared in good to excellent yields using this method. All compounds were evaluated for their anti-proliferative effect against colorectal cell lines. Among them, compound 3ab showed the most potent anti-proliferative activity against the CRC cells, and displayed low toxicity in the normal cell. Further investigation indicated that 3ab could effectively suppress the proliferation and migration of CRC cells, along with inducing cell cycle arrest and apoptosis. Mechanistic studies revealed that compound 3ab inhibited the proliferation of CRC cells via suppressing the AKT/GSK-3ß pathway. In vivo evaluation demonstrated remarkable antitumor effect of 3ab (10 mg/kg) in the HCT116 xenograft model with no obvious toxicity, which is superior to that of 5-Fluorouracil (20 mg/kg). Therefore, conjugate 3ab could be considered as a potential CRC therapy agent for further development.

Clivia biosensor: Soil moisture identification based on electrophysiology signals with deep learning.

Research has shown that plants have the ability to detect environmental changes and generate electrical signals in response. These electrical signals can regulate the physiological state of plants and produce corresponding feedback. This suggests that plants have the potential to be used as biosensors for monitoring environmental information. However, there are current challenges in linking environmental information with plant electrical signals, especially in collecting and classifying the corresponding electrical signals under soil moisture gradients. This study documented the electrical signals of clivia under different soil moisture gradients and created a dataset for classifying electrical signals. Subsequently, we proposed a lightweight convolutional neural network (CNN) model (PlantNet) for classifying the electrical signal dataset. Compared to traditional CNN models, our model achieved optimal classification performance with the lowest computational resource consumption. The model achieved an accuracy of 99.26%, precision of 99.31%, recall of 92.26%, F1-score of 99.21%, with 0.17M parameters, a size of 7.17MB, and 14.66M FLOPs. Therefore, this research provides scientific evidence for the future development of plants as biosensors for detecting soil moisture, and offers insight into developing plants as biosensors for detecting signals such as ozone, PM2.5, Volatile Organic Compounds(VOCs), and more. These studies are expected to drive the development of environmental monitoring technology and provide new pathways for better understanding the interaction between plants and the environment.

Hypoxia-accelerating pyroptosis nanoinducers for promoting image-guided cancer immunotherapy.

Precise image-guided cancer immunotherapy holds immense potential in revolutionizing cancer treatment. The strategies facilitating activatable imaging and controlled therapeutics are highly desired yet to be developed. Herein, we report a new pyroptosis nanoinducer that integrates aggregation-induced emission luminogen (AIEgen) and DNA methyltransferase inhibitor with hypoxia-responsive covalent organic frameworks (COFs) for advanced image-guided cancer immunotherapy. We first synthesize and compare three donor-acceptor type AIEgens featuring varying numbers of electron-withdrawing units, and find that the incorporation of two acceptors yields the longest response wavelength and most effective photodynamic therapy (PDT) property, surpassing the performance of analogs with one or three acceptor groups. A COF-based nanoplatform containing AIEgen and pyroptosis drug is successfully constructed via the one-pot method. The intra-COF energy transfer significantly quenches AIEgen, in which both fluorescence and PDT properties greatly enhance upon hypoxia-triggered COF degradation. Moreover, the photodynamic process exacerbates hypoxia, accelerating pyroptosis drug release. The nanoagent enables sensitive delineation of tumor site through in situ activatable fluorescence signature. Thanks to the exceptional ROS production capabilities and hypoxia-accelerating drug release, the nanoagent not only inhibits primary tumor growth but also impedes the progression of distant tumors in 4T1 tumor-bearing mice through potent pyroptosis-mediated immune response. This research introduces a novel strategy for achieving activatable phototheranostics and self-accelerating drug release for synergetic cancer immunotherapy.

Two-Photon Absorption Aggregation-Induced Emission Luminogen/Paclitaxel Nanoparticles for Cancer Theranostics.

Multifaceted nanoplatforms integrating fluorescence imaging and chemotherapy have garnered acknowledgment for their potential potency in cancer diagnosis and simultaneous in situ therapy. However, some drawbacks remain for traditional organic photosensitizers, such as poor photostability, short excitation wavelength, and shallow penetration depth, which will greatly lower the chemotherapy treatment efficiency. Herein, we present lipid-encapsulated two-photon active aggregation-induced emission (AIE) luminogen and paclitaxel (PTX) nanoparticles (AIE@PTX NPs) with bright red fluorescence emission, excellent photostability, and good biocompatibility. The AIE@PTX NPs exhibit dual functionality as two-photon probes for visualizing blood vessels and tumor structures, achieving penetration depth up to 186 and 120 µm, respectively. Furthermore, the tumor growth of the HeLa-xenograft model can be effectively prohibited after the fluorescence imaging-guided and PTX-induced chemotherapy, which shows great potential in the clinical application of two-photon cell and tumor fluorescence imaging and cancer treatment.

A maize seed variety identification method based on improving deep residual convolutional network.

Seed quality and safety are related to national food security, and seed variety purity is an essential indicator in seed quality detection. This study established a maize seed dataset comprising 5877 images of six different types and proposed a maize seed recognition model based on an improved ResNet50 framework. Firstly, we introduced the ResStage structure in the early stage of the original model, which facilitated the network's learning process and enabled more efficient information propagation across the network layers. Meanwhile, in the later residual blocks of the model, we introduced both the efficient channel attention (ECA) mechanism and depthwise separable (DS) convolution, which reduced the model's parameter cost and enabled the capturing of more precise and detailed features. Finally, a Swish-PReLU mixed activation function was introduced globally to improve the overall predictive power of the model. The results showed that our model achieved an impressive accuracy of 91.23% in corn seed classification, surpassing other related models. Compared with the original model, our model improved the accuracy by 7.07%, reduced the loss value by 0.19, and decreased the number of parameters by 40%. The research suggested that this method can efficiently classify corn seeds, holding significant value in seed variety identification.

Type 2 diabetic mellitus related osteoporosis: focusing on ferroptosis.

With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal bone tissue structure and reduced bone strength in patients with diabetes. Studies have revealed a close association among diabetes, increased fracture risk, and disturbances in iron metabolism. This review explores the concept of ferroptosis, a non-apoptotic cell death process dependent on intracellular iron, focusing on its role in DOP. Iron-dependent lipid peroxidation, particularly impacting pancreatic ß-cells, osteoblasts (OBs) and osteoclasts (OCs), contributes to DOP. The intricate interplay between iron dysregulation, which comprises deficiency and overload, and DOP has been discussed, emphasizing how excessive iron accumulation triggers ferroptosis in DOP. This concise overview highlights the need to understand the complex relationship between T2DM and OP, particularly ferroptosis. This review aimed to elucidate the pathogenesis of ferroptosis in DOP and provide a prospective for future research targeting interventions in the field of ferroptosis.

Janus liposozyme for the modulation of redox and immune homeostasis in infected diabetic wounds.

Diabetic foot ulcers often become infected, leading to treatment complications and increased risk of loss of limb. Therapeutics to manage infection and simultaneously promote healing are needed. Here we report on the development of a Janus liposozyme that treats infections and promotes wound closure and re-epithelialization. The Janus liposozyme consists of liposome-like selenoenzymes for reactive oxygen species (ROS) scavenging to restore tissue redox and immune homeostasis. The liposozymes are used to encapsulate photosensitizers for photodynamic therapy of infections. We demonstrate application in methicillin-resistant Staphylococcus aureus-infected diabetic wounds showing high ROS levels for antibacterial function from the photosensitizer and nanozyme ROS scavenging from the liposozyme to restore redox and immune homeostasis. We demonstrate that the liposozyme can directly regulate macrophage polarization and induce a pro-regenerative response. By employing single-cell RNA sequencing, T cell-deficient Rag1-/- mice and skin-infiltrated immune cell analysis, we further reveal that IL-17-producing γδ T cells are critical for mediating M1/M2 macrophage transition. Manipulating the local immune homeostasis using the liposozyme is shown to be effective for skin wound repair and tissue regeneration in mice and mini pigs.

Probiotics Armed with In Situ Mineralized Nanocatalysts and Targeted Biocoatings for Multipronged Treatment of Inflammatory Bowel Disease.

While oral probiotics show promise in treating inflammatory bowel disease, the primary challenge lies in sustaining their activity and retention within the inflamed gastrointestinal environment. In this work, we develop an engineered probiotic platform that is armed with biocatalytic and inflamed colon-targeting nanocoatings for multipronged management of IBD. Notably, we achieve the in situ growth of artificial nanocatalysts on probiotics through a bioinspired mineralization strategy. The resulting ferrihydrite nanostructures anchored on bacteria exhibit robust catalase-like activity across a broad pH range, effectively scavenging ROS to alleviate inflammation. The further envelopment with fucoidan-based shields confers probiotics with additional inflamed colon-targeting functions. Upon oral administration, the engineered probiotics display markedly improved viability and colonization within the inflamed intestine, and they further elicit boosted prophylactic and therapeutic efficacy against colitis through the synergistic interplay of nanocatalysis-based immunomodulation and probiotics-mediated microbiota reshaping. The robust and multifunctional probiotic platforms offer great potential for the comprehensive management of gastrointestinal disorders.

Design and verification of a new non-contact piezoelectric energy harvester based on a sinusoidal exciting mechanism.

In this paper, a new non-contact rotary piezoelectric energy harvester based on a sinusoidal exciting mechanism has been proposed. The energy transformation is realized in a non-contact form. The sinusoidal orbital rotor can act as a sinusoidal excitation to the contacts, and it can avoid damage to piezoelectric ceramics from direct strikes while bending piezoelectric cantilever beams. After a series of experiments, the prototype demonstrated an excellent output performance. Having explored the influence of the rotation speed on the output voltage, it reaches the peak when the rotation speed is 180 rpm and the maximum voltage is 18.6 V. The relationship between power and voltage was validated with the rise of resistance at the optimum speed. When the resistance is 10 kΩ, the power that arrives at the peak is 1.35 mW, and the maximum voltage is 12.1 V when the resistance is 200 kΩ. Some application experiments have been designed and verify the feasibility of the prototype; it can light up 18 LEDs and power some microelectronic equipment.