Periodontal lesions are common and frustrating diseases that impact life quality. Efforts in this aspect aim at developing local drug delivery systems with better efficacy and less toxicity. Herein, ...inspired by the sting separation behavior of bees, we conduct novel reactive oxygen species (ROS)-responsive detachable microneedles (MNs) that carry antibiotic metronidazole (Met) for controllable periodontal drug delivery and periodontitis treatment. Benefiting from the needle-base separation ability, such MNs can penetrate through the healthy gingival to reach the gingival sulcus's bottom while offering minimal impact to oral function. Besides, as the drug-encapsulated cores were protected by poly (lactic-co-glycolic acid) (PLGA) shells in MNs, the surrounding normal gingival tissue is not affected by Met, resulting in excellent local biosafety. Additionally, with the ROS-responsive PLGA-thioketal-polyethylene glycol MN tips, they can be unlocked to release Met directly around the pathogen under the high ROS in the periodontitis sulcus, bringing about improved therapeutic effects. Based on these characteristics, the proposed bioinspired MNs show good therapeutic results in treating a rat model with periodontitis, implying their potential in periodontal disease.
Chronic pain interferes with daily functioning and is frequently accompanied by depression. Currently, traditional clinic treatments do not produce satisfactory analgesic effects and frequently ...result in various adverse effects. Pathogen recognition receptors (PRRs) serve as innate cellular sensors of danger signals, sense invading microorganisms, and initiate innate and adaptive immune responses. Among them, cGAS-STING alerts on the presence of both exogenous and endogenous DNA in the cytoplasm, and this pathway has been closely linked to multiple diseases, including auto-inflammation, virus infection, and cancer. An increasing numbers of evidence suggest that cGAS-STING pathway involves in the chronic pain process; however, its role remains controversial. In this narrative review, we summarize the recent findings on the involvement of the cGAS-STING pathway in chronic pain, as well as several possible mechanisms underlying its activation. As a new area of research, this review is unique in considering the cGAS-STING pathway in sensory neurons and glial cells as a part of a broader understanding of pain, including potential mechanisms of inflammation, immunity, apoptosis, and autophagy. It will provide new insight into the treatment of pain in the future.
In this paper, Ge0.94Bi0.06Te was firstly fabricated by mechanical alloying. Compared with the Ge0.94Bi0.06Te sample prepared by the melting process, the maximum ZT achieved an improvement from 1.4 ...to 1.8. The thermoelectric performance of Ge0.94Bi0.06Te can be improved through suppressing Ge vacancies and refining grains via mechanical alloying. Further introducing nano-SiC into the matrix of Ge0.94Bi0.06Te improves thermoelectric performance by increasing Seebeck coefficient and reducing thermal conductivity. Meanwhile, the mechanical properties including the microhardness and Young's modulus are also enhanced by dispersing nano-SiC. Consequently, a maximum ZT ~ 2.1 at 723 K was achieved in GeTe-based materials.
Ge0.94Bi0.06Te bulk materials dispersed with nano-SiC exhibit superior thermoelectric and mechanical properties. A maximum ZT ~ 2.1 at 723 K and a maximum microhardness ~ 1.98 GPa at room temperature were achieved in GeTe-based thermoelectric materials. Display omitted
Biopsy is the gold standard for tumor diagnosis, as this technology provides highly detailed and reliable information on tumorigenesis and progression. Resembling the discrete wettability of desert ...beetles, in this study, a fluorescence polymerase chain reaction (F-PCR) microneedle array (MNA) platform is developed for efficient spatial tumor biopsy. This MNA is fabricated by the coupled strategies of bottom-up self-assembly and top-down photolithography; it comprises a hydrophobic silica nanoparticle-assembled substrate and graphene aerogel-hydrogel hybrid microneedle peaks. Benefitting from the hydrophilicity and absorption capacity of its graphene hybrid microneedle peaks, MNA can easily penetrate tissue specimens and collect tumor nucleic acid biomarkers stereoscopically. In addition, because of the discrete wettability of the platform, both tissue fluids and PCR liquids can be easily removed from the substrate, and each microneedle peak is similar to an independent island for directly conducting F-PCR reactions for tumor marker discovery. Based on these advantages, the F-PCR-MNA platform is demonstrated to be ideal for detecting DNA biomarkers of lung carcinoma in standard solutions, mouse tissue samples, and clinical specimens, thus indicating its practical potential as an innovative tumor biopsy system.
Human lung cancer (LC) cells A549/H358, normal lung epithelial cells BEAS-2B, and lung normal fibroblasts (NFs) were cultured, followed by transfection of H358 cells with HOTAIR shRNA. Extracellular ...vesicles (EVs) extracted from H358 cells were identified. The internalization of Dil-labeled-EVs by NFs was tested, and protein levels of cancer-associated fibroblast (CAF) surface markers, inflammatory cytokines, cell proliferation, invasion, and migration, and lncRNA HOTAIR levels were determined. A549 cells were cultured in an H358-EVs-treated conditioned medium of NFs (NFCM), followed by intravenous injection of A549 cells into nude mice. The lesions and Ki-67-positive cells in lung tissues were measured. The results showed that tumor cell-derived EVs (T-EVs) motivated the transformation of NFs into CAFs. Specifically, EVs can be internalized by NFs, and the protein levels of CAF surface markers and inflammation levels were elevated in H358-EVs-treated NFs. The proliferation, invasion, and migration of A549 cells cultured in T-EVs-treated NFCM were increased. H358-EVs carried HOTAIR into NFs and promoted the transformation of NFs into CAFs. Inhibition of HOTAIR partially reversed the promoting effect of H358-EVs on the transformation of NFs into CAFs and invasion and migration of LC cells. T-EVs promoted metastasis of LC in vivo by transforming NFs into CAFs.
Extreme climates can result in marked damage to crop yields and threaten regional and global food security. Maize is a major grain crop in Liaoning Province which is severely affected by dry and hot ...weather events. This study was based on the maize yield and daily meteorological data from various meteorological stations in Liaoning Province from 2000 to 2020. We calculated the standardized dry and hot index and constructed a method for estimating the maize yield reduction risk under compound dry–hot events (CDHE) in Liaoning Province by combining the coefficient of variation in maize yield reduction, yield loss risk index, and the frequency of CDHE during yield reduction. The results showed that the high-risk area for the occurrence of CDHE in maize was Chaoyang City, located in the western part of Liaoning Province. Cities in the low-risk area accounted for approximately 64.3% of the total number of cities in Liaoning Province, mainly in the central and northern parts of Liaoning Province. This study emphasizes the impact of CDHE on agricultural production and provides an index for assessing the risk of CDHE on maize production.
Traditional Chinese medicine, such as
and
, has potential values in treating systemic sclerosis (SSc) and other autoimmune diseases, while their toxic side effect elimination and precise tropical ...drug delivery are still challenges. Here, we present multiple traditional Chinese medicine integrated photoresponsive black phosphorus (BP) microneedles (MNs) with the desired features for the SSc treatment. By employing a template-assisted layer-by-layer curing method, such MNs with triptolide (TP)/paeoniflorin (Pae) needle tips and BP-hydrogel needle bottoms could be well generated. The combined administration of TP and Pae can not only provide anti-inflammatory, detoxification, and immunomodulatory effects to treat skin lesions in the early stage of SSc but also remarkably reduce the toxicity of single drug delivery. Besides, the additive BPs possess good biocompatibility and near-infrared (NIR) responsiveness, imparting the MN photothermal-controlled drug release capability. Based on these features, we have demonstrated that the traditional Chinese medicine integrated responsive MNs could effectively improve skin fibrosis and telangiectasia, reduce collagen deposition, and reduce epidermal thickness in the SSc mouse models. These results indicated that the proposed Chinese medicine integrated responsive MNs had enormous potential in clinical therapy of SSc and other diseases.
Under global climate warming, the global water cycle is further accelerating, the risk of drought is increasing, and the instability and sustainability of agricultural production are seriously ...threatened. Northeast China, as the “granary” of China, located in the mid-high latitudes of the Northern Hemisphere, is one of the regions strongly influenced by droughts. Thus, studying the spatial and temporal distribution of drought is helpful for the development of methods for forecasting potential drought hazards in Northeast China. This study used observed data from 86 meteorological stations in Northeast China from 1961 to 2020 to calculate the standardized precipitation evapotranspiration index (SPEI) at different time scales for the past 60 years and analyzed the spatial and temporal characteristics of drought in Northeast China based on the run theory and the Mann-Kendall test. The SPEI at the annual scale showed decreasing trends with no significant mutation point. Seasonally, there was a decreasing trend of the SPEI in summer and autumn and an increasing trend in spring and winter, which indicates that drought in Northeast China has decreased in winter and spring. The annual drought frequency ranged from 25.5% to 37.6%, and the spatial characteristics of the frequency of moderate drought, severe drought, and extreme drought, respectively, showed the following distribution patterns from the western region to the central region and then to the eastern region of Northeast China: “high-low-high”, “low-high-low”, and “gradually decreasing”.
•A broad range of researches about hierarchical microneedles were reviewed, and were categorized according to their structure and materials.•The fabrication strategies and research progress of ...hierarchical microneedles in the area of biomarkers detection and transdermal drug delivery were discussed.•The challenges and outlook were discussed.
As a new kind of microcarrier device, microneedles are featured by micrometer needle arrays with an overall size in the centimeter scale. Due to the needle shape and the micron size, microneedles can penetrate the skin without harming nerves and blood vessels, which causes many advantages such as minimally invasive, safe and convenient. The past few decades have witnessed a great leap in microneedles research. The main materials of microneedles have changed from metal and ceramic to polymers with more complex functions, and the optimization of materials and preparation strategies has led to a greater variety of microneedle styles. Among them, the construction or combination of smaller size structures or materials on microneedles to fabricate hierarchical microneedles is a major research hotspot. Here, we present the recent research progress of hierarchical microneedles for biomedicine. We begin by discussing the fabrication strategies of hierarchical microneedles, including mainstream casting and coating methods based on microneedle molds and three dimensions (3D) printing methods. We then expand the discussion from the hierarchical microneedles with porous structure to those composited with nanomaterials. Eventually, we have a discussion about the research progress of hierarchical microneedles in the area of biomarkers detection and transdermal drug delivery, as well as its future development direction.
This article analyzes the current status of carbon emission statistical accounting system construction both domestically and internationally, analyzes the six major trends in the changes in carbon ...emission characteristics of electricity under the construction of new power systems, and based on this, proposes a framework for carbon emission statistical accounting system under the new power system, providing basic support for improving electricity carbon emission accounting and carrying out carbon emission control.
