TFEB Probably Involved in Midazolam-Disturbed Lysosomal Homeostasis and Its Induced β-Amyloid Accumulation

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases, and β-amyloid (Aβ) plays a leading role in the pathogenesis of AD. The transcription factor EB (TFEB), a main regulating factor of autophagy and lysosome biosynthesis, is involved in the pathogenesis of AD by regulating autophagy-lysosomal pathways. To date, the choice of anesthetics during surgery in patients with neurodegenerative diseases and evaluation of the effects and underlying mechanisms in these patients have rarely been reported. In this study, the HEK293-APP cells overexpressing APP and Hela cells were used. The cells were treated with midazolam at different concentrations and at different times, then lysosomes were stained by lysotracker and their morphology was observed under a fluorescence microscope. The number and size of lysosomes were analyzed using the ImageJ software. The levels of TFEB in the nucleus and APP-cleaved intracellular proteins were detected by nuclear separation and Western Blot. Finally, ELISA was used to detect the levels of Aβ40 and Aβ42 in the cells after drug treatment. We found that 30 μM midazolam decreased the number of lysosomes and increased its size in HEK293 and HeLa cells. However, 15 μM midazolam transiently disturbed lysosomal homeostasis at 24 h and recovered it at 36 h. Notably, there was no significant difference in the extent to which lysosomal homeostasis was disturbed between treatments of different concentrations of midazolam at 24 h. In addition, 30 μM midazolam prevents the transport of TFEB to the nucleus in either normal or starved cells. Finally, the intracellular C-terminal fragment β (CTFβ), CTFα, Aβ40 and Aβ42 levels were all significantly elevated in 30 μM midazolam-treated HKE293-APP cells. Collectively, the inhibition of TFEB transport to the nucleus may be involved in midazolam-disturbed lysosomal homeostasis and its induced Aβ accumulation in vitro. The results indicated the risk of accelerating the pathogenesis of AD by midazolam and suggested that TFEB might be a candidate target for reduction of midazolam-dependent neurotoxicity

Reclamation-oriented spatiotemporal evolution of coastal wetland along Bohai Rim, China

Coastal wetlands are located in the ecotone of interaction between the land surface and sea, and anthropogenic activities extensively interfere with these wetlands through the reclamation of large tidal wetlands and destruction of the function of the ecosystems. In this study, we investigated the dynamic evolutionary characteristics of the Bohai Rim coastal area over the past 40 years using the Modified Normalized Difference Water Index, the fractal dimension, object-oriented classification, the land-use transfer trajectory, and regression analysis. Additionally, we quantified and monitored the evolution of reclamation and analyzed the correlation between reclamation and coastal wetlands based on 99 Landsat-2, -5, and -8 images (at 60 m and 30 m spatial resolution) over the period 1980-2019. The results are as follows. (1) The coastline of the Bohai Rim increased by 1 631.2 km from 1980 to 2019 with a zigzag variation. The artificial coastline increased by 2 946.1 km, whereas the natural coastline decreased by 90%. (2) The area of man-made wetlands increased by 3 736.9 km(2), the area of construction land increased by 1 008.4 km(2), and the natural wetland area decreased by 66%. The decrease of tidal flats is the main contributor to the decrease of natural wetland area (takes account for 91.1%). Coastal areas are affected by intense human disturbance, which was taken place across a large area of tidal flats and caused the landscape to fragment and be more heterogeneous. The coastal zone development activities were primarily concentrated in the southern Laizhou Bay, the Yellow River Delta, the Bohai Bay, the northern Liaodong Bay, and the Pulandian Bay. The solidified shorelines and increase in sea level have resulted in intertidal wetlands decreasing and impaired wetland ecology. (3) There is a good agreement between reclamation and the size of the coastal wetlands. Both land reclamation and the reduction in coastal wetland areas are significantly related to the population size, fishery output value, and urbanization rate. In summary, human activities, such as the construction of aquaculture ponds and salt pans, industrialization, and urbanization, are the primary forces that influence the environmental changes in the coastal region. This study is beneficial for establishing and improving the systems for the rational development and utilization of natural resources, and provides theoretical references for restoring wetland ecology and managing future reclamation activities in other coastal zone-related areas

A Facile Fabrication of High Toughness Poly(lactic Acid) via Reactive Extrusion with Poly(butylene Succinate) and Ethylene-Methyl Acrylate-Glycidyl Methacrylate

As is an excellent bio-based polymer material, poly(lactic acid) (PLA)’s brittle nature greatly restricts its extensive applications. Herein, poly(butylene succinate) (PBS) was introduced to toughening PLA by melt blending using a self-made triple screw extruder through in situ reactive with ethylene-methyl acrylate-glycidyl methacrylate (EGMA). The effect of EGMA concentrations on the mechanical properties, morphology, interfacial compatibility of PLA/PBS blends were studied. Fourier transform infrared (FT-IR) results demonstrated that the epoxy group of EGMA reacts with the hydroxyl groups of PLA and PBS, which proved the occurrence of interfacial reactions among the tri-component. The significantly improved compatibility between PLA and PBS after EGMA incorporation was made evident by scanning electron microscope (SEM) characterization results. Meanwhile, the contact angle test predicted that the EGMA was selectively localized at the interface between PLA and PBS, and the result was verified by morphological analysis of cryofracture and etched samples. The EGMA improves the compatibility of PLA/PBS blends, and consequently leads to a significantly increased toughness with the elongation at break occurring 83 times more when 10 wt % EGMA was introduced than neat PLA, while impact strength also enhanced by twentyfold. Ultimately, the toughening mechanism of PLA based polymers was established based on the above analysis, exploring a new way for the extensive application for degradable material

Dietary Se-Enriched <i>Cardamine enshiensis</i> Supplementation Alleviates Transport-Stress-Induced Body Weight Loss, Anti-Oxidative Capacity and Meat Quality Impairments of Broilers

The aim of this experiment was to explore the effects of a new selenium (Se) source from Se-enriched Cardamine enshiensis (SeCe) on body weight loss, anti-oxidative capacity and meat quality of broilers under transport stress. A total of 240 one-day-old ROSS 308 broilers were allotted into four treatments with six replicate cages and 10 birds per cage using a 2 × 2 factorial design. The four groups were as follows: (1) Na2SeO3-NTS group, dietary 0.3 mg/kg Se from Na2SeO3 without transport stress, (2) SeCe-NTS group, dietary 0.3 mg/kg Se from SeCe without transport stress, (3) Na2SeO3-TS group, dietary 0.3 mg/kg Se from Na2SeO3 with transport stress, and (4) SeCe-TS group, dietary 0.3 mg/kg Se from SeCe with transport stress. After a 42 d feeding period, the broilers were transported by a lorry or kept in the original cages for 3 h, respectively. The results showed that dietary SeCe supplementation alleviated transport-stress-induced body weight loss and hepatomegaly of the broilers compared with the broilers fed Na2SeO3 diets (p p p 2SeO3, dietary SeCe supplementation alleviates transport-stress-induced body weight loss, anti-oxidative capacity and meat quality impairments of broilers

Ropivacaine-loaded hydrogels for prolonged relief of chemotherapy-induced peripheral neuropathic pain and potentiated chemotherapy

Abstract Chemotherapy can cause severe pain for patients, but there are currently no satisfactory methods of pain relief. Enhancing the efficacy of chemotherapy to reduce the side effects of high-dose chemotherapeutic drugs remains a major challenge. Moreover, the treatment of chemotherapy-induced peripheral neuropathic pain (CIPNP) is separate from chemotherapy in the clinical setting, causing inconvenience to cancer patients. In view of the many obstacles mentioned above, we developed a strategy to incorporate local anesthetic (LA) into a cisplatin-loaded PF127 hydrogel for painless potentiated chemotherapy. We found that multiple administrations of cisplatin-loaded PF127 hydrogels (PFC) evoked severe CIPNP, which correlated with increased pERK-positive neurons in the dorsal root ganglion (DRG). However, incorporating ropivacaine into the PFC relieved PFC-induced CIPNP for more than ten hours and decreased the number of pERK-positive neurons in the DRG. Moreover, incorporating ropivacaine into the PFC for chemotherapy is found to upregulate major histocompatibility complex class I (MHC-I) expression in tumor cells and promote the infiltration of cytotoxic T lymphocytes (CD8+ T cells) in tumors, thereby potentiating chemotherapy efficacy. This study proposes that LA can be used as an immunemodulator to enhance the effectiveness of chemotherapy, providing new ideas for painless cancer treatment

Anatomy and Histochemistry of the Roots and Shoots in the Aquatic Selenium Hyperaccumulator Cardamine hupingshanensis (Brassicaceae)

The perennial selenium (Se) hyperaccumulator Cardamine hupingshanensis (Brassicaceae) thrives in aquatic and subaquatic Se-rich environments along the Wuling Mountains, China. Using bright-field and epifluorescence microscopy, the present study determined the anatomical structures and histochemical features that allow this species to survive in Se-rich aquatic environments. The roots of C. hupingshanensis have an endodermis with Casparian walls, suberin lamellae, and lignified secondary cell walls; the cortex and hypodermal walls have phi (Φ) thickenings; and the mature taproots have a secondary structure with a periderm. The stems possess a lignified sclerenchymal ring and an endodermis, and the pith and cortex walls have polysaccharide-rich collenchyma. Air spaces are present in the intercellular spaces and aerenchyma in the cortex and pith of the roots and shoots. The dense fine roots with lignified Φ thickenings and polysaccharide-rich collenchyma in the shoots may allow C. hupingshanensis to hyperaccumulate Se. Overall, our study elucidated the anatomical features that permit C. hupingshanensis to thrive in Se-rich aquatic environments

Self-Healing Chameleon Skin Functioning in the Air Environments

Chameleons are famous for their uncommon ability to change skin colors rapidly by tuning the lattice distance of guanine nanocrystals within the dermal iridophores. This mechanism has inspired various artificial photonic crystal (PC) films with tunable structural colors. However, the structural colors of most reported films are facile to be destroyed by external factors such as friction, impact, or water evaporation. Herein, an artificial intelligent skin, which has an elastomer–colloidal photonic crystal–hydrogel sandwich structure, is presented in this work. The outer modified polydimethylsiloxane layer acts as the cuticle to protect the hydrogel layer from water evaporation and endows the skin with self-healing ability. The inner hydrophilic hydrogel layer embedded with the colloidal photonic crystals acts as the dermis layer, and the polystyrene colloids layer plays the role of the guanine nanocrystals. A programmed color change can be easily controlled by varying the elongation of the artificial skin, covering the full visible spectrum range. Moreover, skin with patterned stripes, which is similar to the panther chameleon skin that can manipulate multiple colors, has also been achieved. The present artificial skin will offer fresh perspectives on the preparation of artificial chameleon skin similar to the real dynamic flexible skin, which would promote the application of PCs in optical devices

Self-Healing Chameleon Skin Functioning in the Air Environments

Chameleons are famous for their uncommon ability to change skin colors rapidly by tuning the lattice distance of guanine nanocrystals within the dermal iridophores. This mechanism has inspired various artificial photonic crystal (PC) films with tunable structural colors. However, the structural colors of most reported films are facile to be destroyed by external factors such as friction, impact, or water evaporation. Herein, an artificial intelligent skin, which has an elastomer–colloidal photonic crystal–hydrogel sandwich structure, is presented in this work. The outer modified polydimethylsiloxane layer acts as the cuticle to protect the hydrogel layer from water evaporation and endows the skin with self-healing ability. The inner hydrophilic hydrogel layer embedded with the colloidal photonic crystals acts as the dermis layer, and the polystyrene colloids layer plays the role of the guanine nanocrystals. A programmed color change can be easily controlled by varying the elongation of the artificial skin, covering the full visible spectrum range. Moreover, skin with patterned stripes, which is similar to the panther chameleon skin that can manipulate multiple colors, has also been achieved. The present artificial skin will offer fresh perspectives on the preparation of artificial chameleon skin similar to the real dynamic flexible skin, which would promote the application of PCs in optical devices

Self-Healing Chameleon Skin Functioning in the Air Environments

Chameleons are famous for their uncommon ability to change skin colors rapidly by tuning the lattice distance of guanine nanocrystals within the dermal iridophores. This mechanism has inspired various artificial photonic crystal (PC) films with tunable structural colors. However, the structural colors of most reported films are facile to be destroyed by external factors such as friction, impact, or water evaporation. Herein, an artificial intelligent skin, which has an elastomer–colloidal photonic crystal–hydrogel sandwich structure, is presented in this work. The outer modified polydimethylsiloxane layer acts as the cuticle to protect the hydrogel layer from water evaporation and endows the skin with self-healing ability. The inner hydrophilic hydrogel layer embedded with the colloidal photonic crystals acts as the dermis layer, and the polystyrene colloids layer plays the role of the guanine nanocrystals. A programmed color change can be easily controlled by varying the elongation of the artificial skin, covering the full visible spectrum range. Moreover, skin with patterned stripes, which is similar to the panther chameleon skin that can manipulate multiple colors, has also been achieved. The present artificial skin will offer fresh perspectives on the preparation of artificial chameleon skin similar to the real dynamic flexible skin, which would promote the application of PCs in optical devices