Research最新文献

Given the high malignancy of liver cancer and the liver's unique role in immune and metabolic regulation, current treatments have limited efficacy, resulting in a poor prognosis. Hydrogels, soft 3-dimensional network materials comprising numerous hydrophilic monomers, have considerable potential as intelligent drug delivery systems for liver cancer treatment. The advantages of hydrogels include their versatile delivery modalities, precision targeting, intelligent stimulus response, controlled drug release, high drug loading capacity, excellent slow-release capabilities, and substantial potential as carriers of bioactive molecules. This review presents an in-depth examination of hydrogel-assisted advanced therapies for hepatocellular carcinoma, encompassing small-molecule drug therapy, immunotherapy, gene therapy, and the utilization of other biologics. Furthermore, it examines the integration of hydrogels with conventional liver cancer therapies, including radiation, interventional therapy, and ultrasound. This review provides a comprehensive overview of the numerous advantages of hydrogels and their potential to enhance therapeutic efficacy, targeting, and drug delivery safety. In conclusion, this review addresses the clinical implementation of hydrogels in liver cancer therapy and future challenges and design principles for hydrogel-based systems, and proposes novel research directions and strategies.

Hydrogel microparticles have been proved to be curative to diabetic wounds. Current trends focus on the integration of bioactive matrix and their smart stimulus-responsive release to meet the complex demand of regeneration in diabetic wound. In this paper, we present novel stem cell exosome-encapsulated Chinese herb glycyrrhizic acid (GA) hydrogel microparticles for wound healing. The integrated GA endows the hydrogel microparticles with antibacterial properties, while the encapsulated exosomes impart them with pro-angiogenesis ability. In addition, as the black phosphorus is incorporated into these hybrid hydrogel microparticles, the release profile of GA and exosomes could be controllable under near-infrared irradiation due to the excellent photothermal effect of black phosphorus and the reversible phase transformation properties of GA. Based on these features, we have demonstrated that these microparticles can effectively kill bacteria, scavenge free radical, and promote angiogenesis from in vitro experiments. Besides, they could also markedly accelerate the wound healing process by down-regulating inflammation and promoting collagen deposition and angiogenesis in bacteria-infected in vivo diabetic wound. These results indicate that the proposed exosome-integrated GA hydrogel microparticles present great potential for clinical diabetic wound treatment.

[This corrects the article DOI: 10.34133/2022/9873203.].

Impedance metasurfaces enable accurate regulation of acoustic fields. However, they can hardly supply a flexible response as such perfect operation is accompanied by stringent requirements on the design of unit cells. Actually, an arbitrary lossless and passive target impedance matrix requires the tuning of 3 independent real parameters. The set composed of a reflection phase, a transmission amplitude, and a transmission phase, enables the representation of an arbitrary impedance matrix, possibly possessing singular elements. In this paper, a mechanism of phase-amplitude-phase modulation (PAP modulation) is developed for the generic design of the unit cells of acoustic impedance metasurfaces. Adjustable acoustic impedance metasurfaces are further available under this framework. An impedance unit with 3 mobile parts is designed based on this idea. The assembled metasurface can handle different incidences for acoustic field manipulation at a given frequency. Beam steering and beam splitting are considered as demonstration examples and are verified by numerical simulation and experiment. PAP modulation enriches the design of acoustic impedance metasurfaces and extends the range of application of impedance theory.

Background: B-cell receptor-associated protein 31 (BCAP31) has protective effects against alveolar epithelial type II cells (AECII) damage by inhibiting mitochondrial injury in acute lung injury (ALI) induced by lipopolysaccharide (LPS), whereas the precise mechanism is still unclear. It is known that PTEN-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy can remove damaged mitochondria selectively, which may be involved in BCAP31 protection against mitochondrial injury. Methods: In the current study, ALI mice models were established by using surfactant protein C (Sftpc)-BCAP31 transgenic mice (BCAP31^TG mice) and AECII-specific BCAP31 knockout mice (BCAP31^CKO mice) treated with LPS. Results: BCAP31 expression in lung tissue and AECII were inhibited in ALI mice. Under LPS challenge, lower level of BCAP31 was found to correlate positively with pathological injury of the lung, respiratory dysfunction, mortality rates, inflammation response, and AECII damage. Further study showed that down-regulation of BCAP31 induced decreased phosphorylation of PINK1 via reduced binding to PINK1, thereby restraining PINK1/Parkin-mediated mitophagy. Down-regulation of mitophagy promoted mitochondrial injury, as shown by the increase in mitochondrial permeability transition pore opening rate, together with enhanced mitochondrial reactive oxygen species (mROS), which were accompanied by increased cellular apoptosis and reactive oxygen species (ROS). The increased cellular ROS contributed to the inflammatory response via activation of nuclear factor κB (NF-κB). In contrast, BCAP31 overexpression promoted phosphorylation of PINK1 and PINK1/Parkin-mediated mitophagy, thus blocking the mROS/ROS/NF-κB pathway, favoring a protective condition that ultimately led to the inhibition of AECII apoptosis and inflammatory response in LPS-induced ALI. Conclusion: Ultimately, BCAP31 alleviated ALI by activating PINK1/Parkin-mediated mitophagy and blocking the mROS/ROS/NF-κB pathway in AECII.

Neuropathic pain (NP) represents a considerable clinical challenge, profoundly impacting patients' quality of life. Presently, pharmacotherapy serves as a primary approach for NP alleviation, yet its efficacy often remains suboptimal. Melatonin (MLT), a biologically active compound secreted by the pineal gland, has long been associated with promoting and maintaining sleep. Although recent studies suggest analgesic effects of MLT, the underlying mechanism remains largely unknown, particularly its impact on the cortex. In this study, we induced an NP model in mice through spared nerve injury (SNI) and observed a considerable, dose-dependent alleviation in NP symptoms following intraperitoneal or anterior cingulate cortex (ACC) administration of MLT. Our findings further indicated that the NP management of MLT is selectively mediated by MLT-related receptor 2 (MT₂R), rather than MT₁R, on neurons and microglia within the ACC. Transcriptome sequencing, complemented by bioinformatics analysis, implicated MLT in the modulation of Gα(i) and immune-inflammatory signals. Specifically, MLT inhibited the excitability level of pyramidal cells in the ACC by activating the Gα(i) signaling pathway. Simultaneously, MLT attenuated M₁ polarization and promoted M₂ polarization of microglia, thereby mitigating the inflammatory response and type II interferon response within the ACC. These findings unveil a hitherto unrecognized molecular mechanism: an MLT-mediated neuroimmune modulation pathway in the ACC mediated by MT₂R. This elucidation sheds light on the regulatory character of MLT in chronic nociceptive pain conditions, offering a prospective therapeutic strategy for NP management.

The sensorimotor cortex participates in diverse functions with different reciprocally connected subregions and projection-defined pyramidal neuron types therein, while the fundamental organizational logic of its circuit elements at the single-cell level is still largely unclear. Here, using mouse Cre driver lines and high-resolution whole-brain imaging to selectively trace the axons and dendrites of cortical pyramidal tract (PT) and intratelencephalic (IT) neurons, we reconstructed the complete morphology of 1,023 pyramidal neurons and generated a projectome of 6 subregions within the sensorimotor cortex. Our morphological data revealed substantial hierarchical and layer differences in the axonal innervation patterns of pyramidal neurons. We found that neurons located in the medial motor cortex had more diverse projection patterns than those in the lateral motor and sensory cortices. The morphological characteristics of IT neurons in layer 5 were more complex than those in layer 2/3. Furthermore, the soma location and morphological characteristics of individual neurons exhibited topographic correspondence. Different subregions and layers were composed of different proportions of projection subtypes that innervate downstream areas differentially. While the axonal terminals of PT neuronal population in each cortical subregion were distributed in specific subdomains of the superior colliculus (SC) and zona incerta (ZI), single neurons selectively innervated a combination of these projection targets. Overall, our data provide a comprehensive list of projection types of pyramidal neurons in the sensorimotor cortex and begin to unveil the organizational principle of these projection types in different subregions and layers.

Psychedelics have long been recognized not only for their profound impact on human consciousness but also for their potential therapeutic applications. This perspective explores the multifaceted relationship between psychedelics and consciousness, emphasizing their capacity to alter sensory perceptions, disrupt self-referential thought processes, and catalyze profound spiritual and existential experiences. As research advances, psychedelics are being integrated into therapeutic settings, challenging existing psychiatric models and offering new insights into the complex nature of consciousness and mental health. This emerging paradigm marks the need for careful regulation and ethical considerations in the therapeutic use of psychedelics, promising a more holistic approach to mental health disorders.

Precise and timely detection of a crop's nutrient requirement will play a crucial role in assuring optimum plant growth and crop yield. The present study introduces a reliable deep learning platform called "Deep Learning-Crop Platform" (DL-CRoP) for the identification of some commercially grown plants and their nutrient requirements using leaf, stem, and root images using a convolutional neural network (CNN). It extracts intrinsic feature patterns through hierarchical mapping and provides remarkable outcomes in identification tasks. The DL-CRoP platform is trained on the plant image dataset, namely, Jammu University-Botany Image Database (JU-BID), available at https://github.com/urfanbutt. The findings demonstrate implementation of DL-CRoP-cases A (uses shoot images) and B (uses leaf images) for species identification for Solanum lycopersicum (tomato), Vigna radiata (Vigna), and Zea mays (maize), and cases C (uses leaf images) and D (uses root images) for diagnosis of nitrogen deficiency in maize. The platform achieved a higher rate of accuracy at 80-20, 70-30, and 60-40 splits for all the case studies, compared with established algorithms such as random forest, K-nearest neighbor, support vector machine, AdaBoost, and naïve Bayes. It provides a higher accuracy rate in classification parameters like recall, precision, and F1 score for cases A (90.45%), B (100%), and C (93.21), while a medium-level accuracy of 68.54% for case D. To further improve the accuracy of the platform in case study C, the CNN was modified including a multi-head attention (MHA) block. It resulted in the enhancement of the accuracy of classifying the nitrogen deficiency above 95%. The platform could play an important role in evaluating the health status of crop plants along with a role in precise identification of species. It may be used as a better module for precision crop cultivation under limited nutrient conditions.