Preparation of Healthy Single Neuron or Astrocyte Suspension from Adult Mouse Brain for RNA-seq.

Single-cell RNA sequencing (scRNA-seq) has been widely applied in neuroscience research, enabling the investigation of cellular heterogeneity at the transcriptional level, the characterization of rare cell types, and the detailed analysis of the stochastic nature of gene expression. Isolation of single nerve cells in good health, especially from the adult rodent brain, is the most difficult and critical process for scRNA-seq. Here, we describe methods to optimize protease digestion of brain slices, which enable yield of millions of cells in good health from the adult brain.

Gamma-patterned sensory stimulation reverses synaptic plasticity deficits in rat models of early Alzheimer's disease.

Non-invasive sensory stimulation in the range of the brain's gamma rhythm (30-100 Hz) is emerging as a new potential therapeutic strategy for the treatment of Alzheimer's disease (AD). Here, we investigated the effect of repeated combined exposure to 40 Hz synchronized sound and light stimuli on hippocampal long-term potentiation (LTP) in vivo in three rat models of early AD. We employed a very complete model of AD amyloidosis, amyloid precursor protein (APP)-overexpressing transgenic McGill-R-Thy1-APP rats at an early pre-plaque stage, systemic treatment of transgenic APP rats with corticosterone modelling certain environmental AD risk factors and, importantly, intracerebral injection of highly disease-relevant AD patient-derived synaptotoxic beta-amyloid and tau in wild-type animals. We found that daily treatment with 40 Hz sensory stimulation for 2 weeks fully abrogated the inhibition of LTP in all three models. Moreover, there was a negative correlation between the magnitude of LTP and the level of active caspase-1 in the hippocampus of transgenic APP animals, which suggests that the beneficial effect of 40 Hz stimulation was dependent on modulation of pro-inflammatory mechanisms. Our findings support ongoing clinical trials of gamma-patterned sensory stimulation in early AD.

A comparison of the impact on neuronal transcriptome and cognition of rAAV5 transduction with three different doses in the mouse hippocampus.

Introduction: Recombinant adeno-associated viruses (rAAVs) are widely used in genetic therapeutics. AAV5 has shown superior transduction efficiency, targeting neurons and glial cells in primate brains. Nonetheless, the comprehensive impact of AAV5 transduction on molecular and behavioral alterations remains unexplored. This study focuses on evaluating the effects of AAV5 transduction in the hippocampus, a critical region for memory formation and emotional processes. Methods: In this experiment, fluorescence-activated cell sorting (FACS) was utilized to isolate the mCherry-labeled pyramidal neurons in the hippocampus of CaMkIIα-cre mice following three different doses rAAV5-mCherry infusion after 3 weeks, which were then subjected to RNA sequencing (RNA-seq) to assess gene expression profiles. The cytokines concentration, mRNA expression, and glial response in hippocampi were confirmed by ELASA, digital droplet PCR and immunohistochemistry respectively. Locomotion and anxiety-like behaviors were elevated by Open Field Test and Elevated Plus Maze Test, while the Y-Maze were used to assessed spatial working memory. Recognition memory and fear responses were examined by the Novel Object Recognition Test and Fear Conditioning Test, respectively. Results: We found that 2.88 × 1010 v.g rAAV5 transduction significantly upregulated genes related to the immune response and apoptosis, and downregulated genes associated with mitochondrial function and synaptic plasticity in hippocampal pyramidal neurons, while did not induce neuronal loss and gliosis compared with 2.88 × 109 v.g and 2.88 × 108 v.g. Furthermore, the same doses impaired working memory and contextual fear memory, without effects on locomotion and anxiety-related behaviors. Discussion: Our findings highlight the detrimental impact of high-dose administration compared to median-dose or low-dose, resulting in increased neural vulnerability and impaired memory. Therefore, when considering the expression effectiveness of exogenous genes, it is crucial to also take potential side effects into account in clinical settings. However, the precise molecular mechanisms underlying these drawbacks of high-dose rAAV5-mCherry still require further investigation in future studies.

Tau and Amyloid ß Protein in Patient-Derived Aqueous Brain Extracts Act Concomitantly to Disrupt Long-Term Potentiation in Vivo.

Amyloid ß protein (Aß) and tau, the two main proteins implicated in causing Alzheimer's disease (AD), are posited to trigger synaptic dysfunction long before significant synaptic loss occurs in vulnerable circuits. Whereas soluble Aß aggregates from AD brain are well recognized potent synaptotoxins, less is known about the synaptotoxicity of soluble tau from AD or other tauopathy patient brains. Minimally manipulated patient-derived aqueous brain extracts contain the more diffusible native forms of these proteins. Here, we explore how intracerebral injection of Aß and tau present in such aqueous extracts of patient brain contribute to disruption of synaptic plasticity in the CA1 area of the male rat hippocampus. Aqueous extracts of certain AD brains acutely inhibited long-term potentiation (LTP) of synaptic transmission in a manner that required both Aß and tau. Tau-containing aqueous extracts of a brain from a patient with Pick's disease (PiD) also impaired LTP, and diffusible tau from either AD or PiD brain lowered the threshold for AD brain Aß to inhibit LTP. Remarkably, the disruption of LTP persisted for at least 2 weeks after a single injection. These findings support a critical role for diffusible tau in causing rapid onset, persistent synaptic plasticity deficits, and promoting Aß-mediated synaptic dysfunction.SIGNIFICANCE STATEMENT The microtubule-associated protein tau forms relatively insoluble fibrillar deposits in the brains of people with neurodegenerative diseases including Alzheimer's and Pick's diseases. More soluble aggregates of disease-associated tau may diffuse between cells and could cause damage to synapses in vulnerable circuits. We prepared aqueous extracts of diseased cerebral cortex and tested their ability to interfere with synaptic function in the brains of live rats. Tau in these extracts rapidly and persistently disrupted synaptic plasticity and facilitated impairments caused by amyloid ß protein, the other major pathologic protein in Alzheimer's disease. These findings show that certain diffusible forms of tau can mediate synaptic dysfunction and may be a target for therapy.

Death-associated protein kinase 1 is associated with cognitive dysfunction in major depressive disorder.

We previously showed that death-associated protein kinase 1 (DAPK1) expression is increased in hippocampal tissue in a mouse model of major depressive disorde and is related to cognitive dysfunction in Alzheimer's disease. In addition, depression is a risk factor for developing Alzheimer's disease, as well as an early clinical manifestation of Alzheimer's disease. Meanwhile, cognitive dysfunction is a distinctive feature of major depressive disorder. Therefore, DAPK1 may be related to cognitive dysfunction in major depressive disorder. In this study, we established a mouse model of major depressive disorder by housing mice individually and exposing them to chronic, mild, unpredictable stressors. We found that DAPK1 and tau protein levels were increased in the hippocampal CA3 area, and tau was hyperphosphorylated at Thr231, Ser262, and Ser396 in these mice. Furthermore, DAPK1 shifted from axonal expression to overexpression on the cell membrane. Exercise and treatment with the antidepressant drug citalopram decreased DAPK1 expression and tau protein phosphorylation in hippocampal tissue and improved both depressive symptoms and cognitive dysfunction. These results indicate that DAPK1 may be a potential reason and therapeutic target of cognitive dysfunction in major depressive disorder.

Surface-assisted synthesis of biomass carbon-decorated polymer carbon nitride for efficient visible light photocatalytic hydrogen evolution.

Template is frequently studied as a structure-directing agent to tune the nanomorphology of photocatalysts. However, the influences of template on the polymerization of precursors and compositions of the resulting samples are rarely considered. Herein, a biomass carbon-modified graphitic carbon nitride (CCNx) with a thin-layer morphology is synthesized via one-pot surface-assisted polymerization of melamine precursor on organic yeast. The formation of the hydrogen bond between melamine and yeast induces a strong interfacial confinement, giving rise to small-sized CCNx. In addition, the carbon materials derived from yeast dramatically broaden n â†’ π* visible light harvesting, improve electron delocalization, and greatly enhance charge carrier separation. The optimized CCNx presents a much higher photocatalytic hydrogen production rate of 2704 µmol g-1h-1 under visible light irradiation (λ ≥ 420 nm), which is nearly 11-fold that of its pristine counterpart. This work realizes the synergistic effect between morphology tunning and composition tailoring by using biomass template, which shows a great potential in developing efficient metal-free photocatalysts.

Do tau-synaptic long-term depression interactions in the hippocampus play a pivotal role in the progression of Alzheimer's disease?

Cognitive decline in Alzheimer's disease correlates with the extent of tau pathology, in particular tau hyperphosphorylation that initially appears in the transentorhinal and related regions of the brain including the hippocampus. Recent evidence indicates that tau hyperphosphorylation caused by either amyloid-ß or long-term depression, a form of synaptic weakening involved in learning and memory, share similar mechanisms. Studies from our group and others demonstrate that long-term depression-inducing low-frequency stimulation triggers tau phosphorylation at different residues in the hippocampus under different experimental conditions including aging. Conversely, certain forms of long-term depression at hippocampal glutamatergic synapses require endogenous tau, in particular, phosphorylation at residue Ser396. Elucidating the exact mechanisms of interaction between tau and long-term depression may help our understanding of the physiological and pathological functions of tau/tau (hyper)phosphorylation. We first summarize experimental evidence regarding tau-long-term depression interactions, followed by a discussion of possible mechanisms by which this interplay may influence the pathogenesis of Alzheimer's disease. Finally, we conclude with some thoughts and perspectives on future research about these interactions.

High efficiency of in-situ cross-linking and acid triggered drug delivery by introducing tobramycin into injectable and biodegradable hydrogels.

High efficiency of in-situ cross-linking and acid triggered drug delivery is realized by introducing tobramycin into the hydrogels. Injectable and biodegradable hydrogels are prepared through two steps: First generation of reactive aldehyde groups in the sodium alginate (A-Alg) and then introduction of antibiotic tobramycin as cross-linker. Due to the formation of dynamic Schiff base bonds between the amino groups in tobramycin and aldehyde groups in A-Alg, the gelation of hydrogels can be realized immediately. Thus, tobramycin acts well as the first role cross-linker and the hydrogels containing tobramycin can be injected into the wound during the treatment. In addition, the acid from the decomposition of organic compounds by the bacteria can break the cross-linking points previously formed by tobramycin in the hydrogels. Therefore, tobramycin can be released and act as the second role model drug to kill the bacteria. Because the hydrogels network is broken, the release of tobramycin is more efficient than the traditional drug delivery from hydrogels by diffusion. Based on these unique properties, the present hydrogels containing tobramycin exhibit a good injectable and biodegradable capability. In addition, due to the existence of the reversible acid-labile linkages in the hydrogels, the hydrogels containing tobramycin are also self-healing, which additionally is favorable for the application of wound dressing. More importantly, the antibacterial hydrogels also demonstrate good biocompatibility in vitro and significantly therapeutic effects on an infected mice model in vivo. Based on the above special properties, the hydrogels cross-linked by tobramycin indicate a new approach to prepare hydrogel dressings with low-cost, non-toxicity and good anti-bacterial performance in the treatment of infectious wounds.

Astrocytes Mediate Cholinergic Regulation of Adult Hippocampal Neurogenesis and Memory Through M1 Muscarinic Receptor.

BACKGROUND: In the neurogenic niches of the adult hippocampus, new functional neurons are continuously generated throughout life, and generation of these neurons has been implicated in learning and memory. Astrocytes, as components of the neurogenic niches, are critical in the regulation of adult hippocampal neurogenesis (AHN). However, little is known about how astrocytes receive and respond to extrinsic cues to regulate AHN. METHODS: By using a transgenic strategy to conditionally delete astrocytic CRHM1 in mice and AAV (adeno-associated virus)-mediated overexpression of astrocytic CHRM1 specifically in the hippocampal dentate gyrus, we systematically investigated the role of astrocytic CHRM1 in the regulation of AHN and the underlying mechanisms using the combined approaches of immunohistochemistry, retrovirus labeling, electrophysiology, primary astrocyte cultures, immunoblotting, and behavioral assays. RESULTS: We report that genetic ablation of CHRM1 in astrocytes led to defects in neural stem cell survival, neuronal differentiation, and maturation and integration of newborn neurons in the dentate gyrus. Astrocytic CHRM1-mediated modulation of AHN was mediated by BDNF (brain-derived neurotrophic factor) signaling. Furthermore, CHRM1 ablation in astrocytes impaired contextual fear memory. These impairments in both AHN and memory were rescued by overexpression of astrocytic CHRM1 in the dentate gyrus. CONCLUSIONS: Our findings reveal a critical role for astrocytes in mediating cholinergic regulation of AHN and memory through CHRM1.

Long-Term Depression-Inducing Low Frequency Stimulation Enhances p-Tau181 and p-Tau217 in an Age-Dependent Manner in Live Rats.

BACKGROUND: Cognitive decline in Alzheimer's disease (AD) correlates with the extent of tau pathology, in particular tau hyperphosphorylation, which is strongly age-associated. Although elevation of cerebrospinal fluid or blood levels of phosphorylated tau (p-Tau) at residues Thr181 (p-Tau181), Thr217 (p-Tau217), and Thr231 (p-Tau231) are proposed to be particularly sensitive markers of preclinical AD, the generation of p-Tau during brain activity is poorly understood. OBJECTIVE: To study whether the expression levels of p-Tau181, p-Tau217, and p-Tau231 can be enhanced by physiological synaptic long-term depression (LTD) which has been linked to the enhancement of p-Tau in hippocampus. METHODS: In vivo electrophysiology was performed in urethane anesthetized young adult and aged male rats. Low frequency electrical stimulation (LFS) was used to induce LTD at CA3 to CA1 synapses. The expression level of p-Tau and total tau was measured in dorsal hippocampus using immunofluorescent staining and/or western blotting. RESULTS: We found that LFS enhanced p-Tau181 and p-Tau217 in an age-dependent manner in the hippocampus of live rats. In contrast, phosphorylation at residues Thr231, Ser202/Thr205, and Ser396 appeared less sensitive to LFS. Pharmacological antagonism of either N-methyl-D-aspartate or metabotropic glutamate 5 receptors inhibited the elevation of both p-Tau181 and p-Tau217. Targeting the integrated stress response, which increases with aging, using a small molecule inhibitor ISRIB, prevented the enhancement of p-Tau by LFS in aged rats. CONCLUSION: Together, our data provide a novel in vivo means to uncover brain plasticity-related cellular and molecular processes of tau phosphorylation at key sites in health and aging.

Effect of Thermal Stimulus on Kinetic Rehydration of Thermoresponsive Poly(diethylene glycol monomethyl ether methacrylate)-block-poly(poly(ethylene glycol) methyl ether methacrylate) Thin Films Probed by In Situ Neutron Reflectivity.

The kinetic rehydration of thin di-block copolymer poly(diethylene glycol monomethyl ether methacrylate)-block-poly(poly(ethylene glycol) methyl ether methacrylate) (PO2-b-PO300) films containing two thermoresponsive components is probed by in situ neutron reflectivity (NR) with different thermal stimuli in the D2O vapor atmosphere. The transition temperatures (TTs) of PO2 and PO300 blocks are 25 and 60 °C, respectively. After the one-step stimulus (rapid decrease in temperature from 60 to 20 °C), the film directly switches from a collapsed to a fully swollen state. The rehydration process is divided into four steps: (a) D2O condensation, (b) D2O absorption, (c) D2O evaporation, and (d) film reswelling. However, the film presents a different rehydration behavior when the thermal stimulus is separated into two smaller steps (first decrease from 60 to 40 °C and then to 20 °C). The film first switches from a collapsed to a semiswollen state caused by the rehydrated PO300 blocks after the first step of thermal stimulus (60 to 40 °C) and then to a swollen state induced by the rehydrated PO2 blocks after the second step (40 to 20 °C). Thus, the kinetic responses are distinct from that after the one-step thermal stimulus. Both the time and extent of condensation as well as evaporation processes are significantly reduced in these two smaller steps. However, the final states of the rehydrated PO2-b-PO300 films are basically identical irrespective of the applied thermal stimulus. Thus, the final state of thermoresponsive di-block copolymer films is not affected by the external thermal stimuli, which is beneficial for the design and preparation of sensors or switches based on thermoresponsive polymer films.

Inhibition of the ISR abrogates mGluR5-dependent long-term depression and spatial memory deficits in a rat model of Alzheimer's disease.

Soluble amyloid-ß-protein (Aß) oligomers, a major hallmark of AD, trigger the integrated stress response (ISR) via multiple pathologies including neuronal hyperactivation, microvascular hypoxia, and neuroinflammation. Increasing eIF2α phosphorylation, the core event of ISR, facilitates metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD), and suppressing its phosphorylation has the opposite effect. Having found the facilitation of mGluR5-LTD by Aß in live rats, we wondered if suppressing eIF2α phosphorylation cascade would protect against the synaptic plasticity and cognitive disrupting effects of Aß. We demonstrate here that the facilitation of mGluR5-LTD in a delayed rat model by single i.c.v. injection of synthetic Aß1-42. Systemic administration of the small-molecule inhibitor of the ISR called ISRIB (trans-isomer) prevents Aß-facilitated LTD and abrogates spatial learning and memory deficits in the hippocampus in exogenous synthetic Aß-injected rats. Moreover, ex vivo evidence indicates that ISRIB normalizes protein synthesis in the hippocampus. Targeting the ISR by suppressing the eIF2α phosphorylation cascade with the eIF2B activator ISRIB may provide protective effects against the synaptic and cognitive disruptive effects of Aß which likely mediate the early stage of sporadic AD.

PV network plasticity mediated by neuregulin1-ErbB4 signalling controls fear extinction.

Neuroplasticity in the medial prefrontal cortex (mPFC) is essential for fear extinction, the process of which forms the basis of the general therapeutic process used to treat human fear disorders. However, the underlying molecules and local circuit elements controlling neuronal activity and concomitant induction of plasticity remain unclear. Here we show that sustained plasticity of the parvalbumin (PV) neuronal network in the infralimbic (IL) mPFC is required for fear extinction in adult male mice and identify the involvement of neuregulin 1-ErbB4 signalling in PV network plasticity-mediated fear extinction. Moreover, regulation of fear extinction by basal medial amygdala (BMA)-projecting IL neurons is dependent on PV network configuration. Together, these results uncover the local molecular circuit mechanisms underlying mPFC-mediated top-down control of fear extinction, suggesting alterative therapeutic approaches to treat fear disorders.

Distinct roles of astroglia and neurons in synaptic plasticity and memory.

Long-term potentiation (LTP) in the hippocampus is the most studied form of synaptic plasticity. Temporal integration of synaptic inputs is essential in synaptic plasticity and is assumed to be achieved through Ca2+ signaling in neurons and astroglia. However, whether these two cell types play different roles in LTP remain unknown. Here, we found that through the integration of synaptic inputs, astrocyte inositol triphosphate (IP3) receptor type 2 (IP3R2)-dependent Ca2+ signaling was critical for late-phase LTP (L-LTP) but not early-phase LTP (E-LTP). Moreover, this process was mediated by astrocyte-derived brain-derived neurotrophic factor (BDNF). In contrast, neuron-derived BDNF was critical for both E-LTP and L-LTP. Importantly, the dynamic differences in BDNF secretion play a role in modulating distinct forms of LTP. Moreover, astrocyte- and neuron-derived BDNF exhibited different roles in memory. These observations enriched our knowledge of LTP and memory at the cellular level and implied distinct roles of astrocytes and neurons in information integration.

Distinct projections from the infralimbic cortex exert opposing effects in modulating anxiety and fear.

Anxiety-related disorders can be treated by cognitive therapies and transcranial magnetic stimulation, which involve the medial prefrontal cortex (mPFC). Subregions of the mPFC have been implicated in mediating different and even opposite roles in anxiety-related behaviors. However, precise causal targets of these top-down connections among diverse possibilities have not been established. Here, we show that the lateral septum (LS) and the central nucleus of the amygdala (CeA) represent 2 direct targets of the infralimbic cortex (IL), a subregion of the mPFC that modulates anxiety and fear. Two projections were unexpectedly found to exert opposite effects on the anxious state and learned freezing: the IL-LS projection promoted anxiety-related behaviors and fear-related freezing, whereas the IL-CeA projection exerted anxiolytic and fear-releasing effects for the same features. Furthermore, selective inhibition of corresponding circuit elements showed opposing behavioral effects compared with excitation. Notably, the IL-CeA projection implemented top-down control of the stress-induced high-anxiety state. These results suggest that distinct IL outputs exert opposite effects in modulating anxiety and fear and that modulating the excitability of these projections with distinct strategies may be beneficial for the treatment of anxiety disorders.

Enduring glucocorticoid-evoked exacerbation of synaptic plasticity disruption in male rats modelling early Alzheimer's disease amyloidosis.

Synaptic dysfunction is a likely proximate cause of subtle cognitive impairment in early Alzheimer's disease. Soluble oligomers are the most synaptotoxic forms of amyloid ß-protein (Aß) and mediate synaptic plasticity disruption in Alzheimer's disease amyloidosis. Because the presence and extent of cortisol excess in prodromal Alzheimer's disease predicts the onset of cognitive symptoms we hypothesised that corticosteroids would exacerbate the inhibition of hippocampal synaptic long-term potentiation in a rat model of Alzheimer's disease amyloidosis. In a longitudinal experimental design using freely behaving pre-plaque McGill-R-Thy1-APP male rats, three injections of corticosterone or the glucocorticoid methylprednisolone profoundly disrupted long-term potentiation induced by strong conditioning stimulation for at least 2 months. The same treatments had a transient or no detectible detrimental effect on synaptic plasticity in wild-type littermates. Moreover, corticosterone-mediated cognitive dysfunction, as assessed in a novel object recognition test, was more persistent in the transgenic animals. Evidence for the involvement of pro-inflammatory mechanisms was provided by the ability of the selective the NOD-leucine rich repeat and pyrin containing protein 3 (NLRP3) inflammasome inhibitor Mcc950 to reverse the synaptic plasticity deficit in corticosterone-treated transgenic animals. The marked prolongation of the synaptic plasticity disrupting effects of brief corticosteroid excess substantiates a causal role for hypothalamic-pituitary-adrenal axis dysregulation in early Alzheimer's disease.

Impaired calcium signaling in astrocytes modulates autism spectrum disorder-like behaviors in mice.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder. The mechanisms underlying ASD are unclear. Astrocyte alterations are noted in ASD patients and animal models. However, whether astrocyte dysfunction is causal or consequential to ASD-like phenotypes in mice is unresolved. Type 2 inositol 1,4,5-trisphosphate 6 receptors (IP3R2)-mediated Ca2+ release from intracellular Ca2+ stores results in the activation of astrocytes. Mutations of the IP3R2 gene are associated with ASD. Here, we show that both IP3R2-null mutant mice and astrocyte-specific IP3R2 conditional knockout mice display ASD-like behaviors, such as atypical social interaction and repetitive behavior. Furthermore, we show that astrocyte-derived ATP modulates ASD-like behavior through the P2X2 receptors in the prefrontal cortex and possibly through GABAergic synaptic transmission. These findings identify astrocyte-derived ATP as a potential molecular player in the pathophysiology of ASD.

Hydration and Thermal Response Kinetics of a Cross-Linked Thermoresponsive Copolymer Film on a Hydrophobic PAN Substrate Coating Probed by In Situ Neutron Reflectivity.

The hydration and thermal response kinetics of the cross-linked thermoresponsive copolymer poly((diethylene glycol monomethyl ether methacrylate)-co-poly(ethylene glycol) methyl ether methacrylate), abbreviated as P(MEO2MA-co-OEGMA300), thin film on a hydrophobic polyacrylonitrile (PAN) substrate coating, which resembles a synthetic fabric, is probed by in situ neutron reflectivity (NR). The PAN and monomer (MEO2MA and OEGMA300) solutions are sequentially spin-coated onto a silicon (Si) substrate. Afterward, plasma treatment is applied to realize the cross-linking of PAN and monomers. The as-prepared cross-linked P(MEO2MA-co-OEGMA300) film on the hydrophobic PAN substrate coating presents a two-layer structure: a substrate-near layer, which is a mixture of PAN and P(MEO2MA-co-OEGMA300), and a main layer, which is composed of pure hydrophilic P(MEO2MA-co-OEGMA300). During hydration in D2O vapor atmosphere, the hydrophobic PAN component prevents the formation of D2O enrichment in the substrate-near layer. However, an additional vapor-near layer is observed on top of the main layer, which is enriched with D2O. The hydration process is constrained by the cross-linking points in the film, inducing the relaxation time to be longer than that in a spin-coated P(MEO2MA-co-OEGMA300) film. Because the as-prepared cross-linked film presents a transition temperature (TT) at 38 °C, the hydrated film switches to the collapsed state when the temperature is increased from 23 to 50 °C. The response to a thermal stimulus is also slower due to the existence of the internal cross-linking points as compared to the spin-coated film. Interestingly, no reswelling is observed at the end of the thermal stimulus, which can be also attributed to the presence of internal cross-linking points.

Citrus Physiological and Molecular Response to Boron Stresses.

Since the essentiality of boron (B) to plant growth was reported nearly one century ago, the implication of B in physiological performance, productivity and quality of agricultural products, and the morphogenesis of apical meristem in plants has widely been studied. B stresses (B deficiency and toxicity), which lead to atrophy of canopy and deterioration of Citrus fruits, have long been discovered in citrus orchards. This paper reviews the research progress of B stresses on Citrus growth, photosynthesis, light use efficiency, nutrient absorption, organic acid metabolism, sugar metabolism and relocation, and antioxidant system. Moreover, the beneficial effects of B on plant stress tolerance and further research in this area were also discussed.

Wearable Bracelet Monitoring the Solar Ultraviolet Radiation for Skin Health Based on Hybrid IPN Hydrogels.

The risk of extensive exposure of the human epidermis to solar ultraviolet radiation is significantly increased nowadays. It not only induces skin aging and solar erythema but also increases the possibility of skin cancer. Therefore, a simply prepared, highly sensitive, and optically readable device for monitoring the solar ultraviolet radiation is highly desired for the skin health management. Because of the photoinitiated polymerization triggered by graphene-carbon nitride (g-C3N4) under ultraviolet radiation, g-C3N4 is homogeneously distributed in the hybrid hydrogels containing N-isopropylacrymide (NIPAM), poly(ethylene glycol) methyl ether methacrylate (OEGMA300), and sodium alginate (SA). By further immersing the hybrid hydrogels into calcium chloride solution, hybrid alginate-Ca2+/P(NIPAM-co-OEGMA300)/g-C3N4 interpenetrating polymeric network (IPN) hydrogels are obtained. Due to the homogeneous distribution of g-C3N4 and the existence of thermoresponsive polymers, the hybrid IPN hydrogels present good adsorption capability and high degradation efficiency for methylene blue (MB) especially at high temperature under ultraviolet radiation. Based on this unique property, the bracelet monitoring skin health is prepared by simply immersing the hybrid IPN hydrogels into the MB solution and then wrapping it with PET foil. Because the immersion time for the top, middle, and bottom parts of the hybrid IPN hydrogels is gradually increased, their colors vary from light to dark blue. A longer time is required for the discoloration of the darker part under solar ultraviolet radiation. Thus, the bracelet can be used to conveniently monitor the dose of solar ultraviolet radiation by simply checking the discoloration in the bracelet under sunshine. Due to the facile preparation and low cost of the bracelet, it is a promising candidate for wearable devices for skin health management.