The reversible piezochromic luminescence behavior of carbon dots under a cycle of loading/unloading pressure.

Carbon dots (CDs) have gained intensive interest owing to their small size, unique structure, excellent photoluminescence (PL) properties and broad applications. In particular, pressure-triggered irreversible piezochromic behavior of fluorescent CDs was previously reported and attributed to the sp2-sp3 transition in the carbon core or aggregation-induced emission under high pressure. Here, we report the reversible piezochromic behavior of microwave-heating synthesized CDs (named M-CDs) using ethylenediamine and aspartic acid as precursors. Under a loading/unloading cycle, the PL intensity of M-CDs decreased continuously with the pressure increasing from 101 kPa up to 20 GPa, and the maximum emission of M-CDs at 101 kPa (λmax = 550 nm) was slightly blue-shifted to 541 nm at 20 GPa, but when the pressure was released from 20 GPa to normal environmental conditions, both the emission wavelength and the PL intensity of M-CDs returned to their initial states at 101 kPa. The control sample was also synthesized using the same precursors but through a hydrothermal method and thus named H-CDs. Both H-CDs and M-CDs have similar particle sizes, morphology and excitation-dependent PL behavior under 101 kPa; however, H-CDs showed a typical piezochromic behavior with the emission blue-shifted from 518 to 491 nm when the pressure was increased from 101 kPa to 0.97 GPa, and then red-shifted from 491 to 530 nm when the pressure was increased up to 10.53 GPa. This irreversible behavior of H-CDs was accompanied by a 2-fold enhancement of their PL intensity after releasing the pressure. The remarkable different behaviors of M-CDs and H-CDs under a loading/unloading cycle are caused by different interior structures of M-CDs and H-CDs due to different synthetic processes, which is worthy of further research.

m6A modification of lncRNA PHKA1-AS1 enhances Actinin Alpha 4 stability and promotes non-small cell lung cancer metastasis.

Cancer is a disease with molecular heterogeneity that is closely related to gene mutations and epigenetic changes. The principal histological subtype of lung cancer is non-small cell lung cancer (NSCLC). Long noncoding RNA (lncRNA) is a kind of RNA that is without protein coding function, playing a critical role in the progression of cancer. In this research, the regulatory mechanisms of lncRNA phosphorylase kinase regulatory subunit alpha 1 antisense RNA 1 (PHKA1-AS1) in the progression of NSCLC were explored. The increased level of N6-methyladenosine (m6A) modification in NSCLC caused the high expression of PHKA1-AS1. Subsequently, high-expressed PHKA1-AS1 significantly facilitated the proliferation and metastasis of NSCLC cells, and these effects could be reversed upon the inhibition of PHKA1-AS1 expression, both in vivo and in vitro. Additionally, the target protein of PHKA1-AS1 was actinin alpha 4 (ACTN4), which is known as an oncogene. Herein, PHKA1-AS1 could enhance the protein stability of ACTN4 by inhibiting its ubiquitination degradation process, thus exerting the function of ACTN4 in promoting the progress of NSCLC. In conclusion, this research provided a theoretical basis for further exploring the potential mechanism of NSCLC metastasis and searching novel biomarkers related to the pathogenesis and progression of NSCLC.

Direct synthesis of branched amines enabled by dual-catalyzed allylic C─H amination of alkenes with amines.

Direct conversion of hydrocarbons into amines represents an important and atom-economic goal in chemistry for decades. However, intermolecular cross-coupling of terminal alkenes with amines to form branched amines remains extremely challenging. Here, a visible-light and Co-dual catalyzed direct allylic C─H amination of alkenes with free amines to afford branched amines has been developed. Notably, challenging aliphatic amines with strong coordinating effect can be directly used as C─N coupling partner to couple with allylic C─H bond to form advanced amines with molecular complexity. Moreover, the reaction proceeds with exclusive regio- and chemoselectivity at more steric hinder position to deliver primary, secondary, and tertiary aliphatic amines with diverse substitution patterns that are difficult to access otherwise.

Impaired Ability in Visual-Spatial Attention in Chinese Children With Developmental Dyslexia.

A growing body of evidence suggests that children with dyslexia in alphabetic languages exhibit visual-spatial attention deficits that can obstruct reading acquisition by impairing their phonological decoding skills. However, it remains an open question whether these visual-spatial attention deficits are present in children with dyslexia in non-alphabetic languages. Chinese, with its logographic writing system, offers a unique opportunity to explore this question. The presence of visual-spatial attention deficits in Chinese children with dyslexia remains insufficiently investigated. Therefore, this study aimed to explore whether such deficits exist, employing a visual search paradigm. Three visual search tasks were conducted, encompassing two singleton feature search tasks and a serial conjunction search task. The results indicated that Chinese children with dyslexia performed as well as chronological age-matched control children in color search tasks but less effectively in orientation search, suggesting a difficulty in the rapid visual processing of orientation: a deficit potentially specific to Chinese dyslexia. Crucially, Chinese children with dyslexia also exhibited lower accuracy, longer reaction times, and steeper slopes in the reaction times by set size function in the conjunction search task compared to control children, which is indicative of a visual-spatial attention deficit.

Transparent multifunctional cellulose-based conductive hydrogel for wearable strain sensors and arrays.

Conductive hydrogels as promising candidate materials for flexible strain sensors have gained considerable attentions. However, it is still a great challenge to construct hydrogel with multifunctional performance via natural polymer. Herein, a novel multifunctional conductive hydrogel based on methylcellulose and cellulose nanocrystal was prepared via a facile and low-cost strategy. Methylcellulose (MC) was introduced to not only guarantee the stability of tannic acid coated cellulose nanocrystal (TA@CNCs) in LiCl solution, but also improve anti-freezing ability. The obtained hydrogel exhibited high transparency (98 % at 800 nm), good stretchability (663.1 %), low temperature tolerance (-23.9 °C), superior conductivity (2.89 S/m) and excellent UV shielding behavior. Flexible strain sensor assembled by the prepared hydrogels can be used to detect human body motions include subtle and large motions, and exhibited good sensitivity and stability over a wide temperature range. Multiple flexible hydrogels can also be assembled into a 3D sensor array to detect the distribution and magnitude of spatial pressure. Therefore, the hydrogels prepared via natural polymers will have broad application prospects in wearable devices, electronic skin and multifunctional sensor components.

Core-shell structured carbon dots with up-conversion fluorescence and photo-triggered nitric oxide-releasing properties.

Cancer-targeted nanotechnology has a new trend in the design and preparation of new materials with functions for imaging and therapeutic applications simultaneously. As a new type of carbon nanomaterial, the inherent core-shell structured carbon dots (CDs) can be designed to provide a modular nanoplatform for integration of bioimaging and therapeutic capabilities. Here, core-shell structured CDs are designed and synthesized from levofloxacin and arginine and named Arg-CDs, in which levofloxacin-derived chromophores with up-conversion fluorescence are densely packed into the carbon core while guanidine groups are located on the shell, providing nitric oxide (NO) for photodynamic therapy of tumors. Moreover, the chromophores in the carbon core irradiated by visible LED light generate large amounts of reactive oxygen species (ROSs) that will oxidize the guanidine groups located on the shell of the Arg-CDs and further increase the NO releasing capacity remarkably. The as-synthesized Arg-CDs show excellent biocompatibility, bright up-conversion fluorescence, and a light-controlled ROS & NO releasing ability, which can be a potential light-modulated nanoplatform to integrate bioimaging and therapeutic functionalities.

A standard procedure for rapid toxicity evaluation of carbon dots both in vitro and in vivo.

Carbon dots (CDs) are an emerging class of fluorescent quantum dot nanomaterials that have attracted considerable scientific attention for biomedical or bioimaging applications due to their physicochemical and biochemical properties. With the emergence of massive novel synthetic CDs applying to biomedical fields of science, evaluating their biosafety before any biological application is essential. However, there is no universal protocol or routine procedures for toxicity detection and biosafety assessment of CDs in general biological environments. Herein, we provide an ideal and fast operating system to detect the biotoxicity of CDs, which has been preliminary practiced. Briefly, the obtained CDs will be evaluated by in vitro cytotoxicity assay using cell counting kit-8, lactate dehydrogenase assay kit, and flow cytometry. Meanwhile, the model creature zebrafish is employed to perform in vivo evaluation by measuring body length, hatching rate, heart rate, and morphological observation. Our operating procedure condenses previous scattered biosafety detection methods into a rapid standard evaluation protocol that can be applied to early biotoxicity screening of CDs. This protocol will accelerate CDs biological exploitation and guide future industrialized biosafety assessment in large-scale applications.

Electroacupuncture alleviates ciliary muscle cell apoptosis in lens-induced myopic guinea pigs through inhibiting the mitochondrial signaling pathway.

AIM: To investigate the effect of electroacupuncture (EA) on the mitochondria-dependent apoptotic signaling pathway in the ciliary muscle of guinea pigs with negative lens-induced myopia (LIM). METHODS: Guinea pigs were randomly divided into normal control (NC) group, LIM group, LIM+SHAM acupoint (LIM+SHAM) group, and LIM+EA group. Animals in the NC group received no intervention, while those in other three groups were covered with -6.0 diopter (D) lenses on right eyes. Meanwhile, animals in the LIM+EA group received EA at Hegu (LI4) combined with Taiyang (EX-HN5) acupoints, while those in the LIM+SHAM group were treated at sham points. After treatments for 1, 2, and 4wk, morphological changes in ciliary muscles were observed with hematoxylin and eosin (H&E) staining and nick end labeling (TUNEL), and the expression of the mitochondrial apoptotic signaling pathway-related molecules in ciliary muscles was measured by real-time quantitative polymerase chain reaction (qPCR) and Western blot. Additionally, the adenosine triphosphate (ATP) contents were also determined in ciliary muscles. RESULTS: Axial length increased significantly in the LIM and LIM+SHAM groups and decreased in the LIM+EA group. The ciliary muscle fibers were broken and destroyed in both LIM and LIM+SHAM groups, whereas those in the LIM+EA group improved significantly. TUNEL assay showed the number of apoptotic cells increased in the LIM and LIM+SHAM groups, whereas reduced in the LIM+EA group. ATP contents showed a significant decrease in the LIM and LIM+SHAM groups, whereas increased after EA treatment. Compared with the NC group, the dynamin-related protein 1 (DRP1), Caspase3, and apoptotic protease activator 1 (APAF1) levels were significantly increased in the LIM group and decreased in the LIM+EA group. CONCLUSION: The results provide evidence of EA inhibiting the development of myopia by regulating the mitochondrial apoptotic signaling pathway.

Surface modification of chitin nanofibers with dopamine as efficient nanosorbents for enhanced removal of dye pollution and metal ions.

The development of environmentally friendly and low-cost adsorbents with high adsorption capacity remains a challenge. Herein, chitin nanofiber-polydopamine composite materials (CNDA) have been obtained by surface modification of chitin nanofiber using dopamine. According to the results of transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier Transform Infrared Spectrometer (FTIR), and X-ray photoelectron spectrometer (XPS), polydopamine have been successfully coated on the surface of chitin nanofiber (ChNF). The ability to remove methylene blue (MB) has been analyzed via standard adsorption experiments, indicating that the maximum adsorption capacity (qmax) can reach 196.6 mg/g at MB initial concentration of 50 mg/L. Most importantly, the adsorption kinetics, isotherm, and thermodynamics were used to investigate the MB adsorption mechanism on composites. This indicated that the polydopamine on the surface of chitin nanofiber (ChNF) plays an important role in the MB dye adsorption. Moreover, the removal ability of CNDA to metal ions has also been investigated, indicating high capacities for Fe3+, Mn2+, Cu2+, and Ni2+. Based on their biodegradability and good adsorption capacity, the CNDA composite material can be considered a promising adsorbent for wastewater treatment.

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Since December 2019, coronavirus disease 2019 (COVID-19) has been rapidly spreading worldwide and affecting the physical and mental health of the general population. It may have even more serious potential harm to children with autism spectrum disorder (ASD). This paper provides a literature review on the psychological and behavioral problems experienced by children with ASD during the COVID-19 epidemic, as well as the factors influencing these issues. The findings of this review can serve as a basis for clinical research on ASD children.

Meticulously Designed Carbon Dots as Photo-Triggered RNA-Destroyer for Evoking Pyroptosis.

An ideal photosensitizer for photodynamic therapy should not only possess high reactive oxygen species (ROS) generation efficiency but also maximize utilization of the in situ produced ROS species, where the latter is closely related to its intracellular location. However, rational design of such photosensitizer without tedious conjugation procedures remains a grand challenge. Here, we report the one-pot preparation of carbon dots (CDs)-based photosensitizer from levofloxacin and neutral red featuring both high 1O2 quantum yield (φΔ = 38.85%) and superior RNA selectivity. Moreover, the φΔ value shows a further 40% improvement and reaches 54.33% in response to RNA binding. Owing to these combined attributes, the CDs could exert great damage to the cellular RNA system (termed the RNA-destroyer) under extremely low dosage of light irradiation (15 mW cm-2, 1 min). It induces pyroptotic cell death and causes rapid release of different cytokines that served as molecular markers in photodynamic immunotherapy. This work represents the meticulously designed CDs with high ROS generation and utilization efficiency via good organization of the photosensitive and targeting modularity. Moreover, it is the first CDs-based pyroptosis inducer to the best of our knowledge.

Photochemical Route for Synthesizing Atomically Precise Metal Nanoclusters from Disulfide.

Practical approaches to the synthesis of atomically precise metal nanoclusters are in high demand as they provide the structural basis for investigating nanomaterials' structure-property correlations with atomic precision. The Brust-Schiffrin method has been widely used, while the essential reductive ligands (e.g., thiols) limit the application of this method for synthesizing metal nanoclusters with specific frameworks and surface ligands. In this work, we developed a photochemical route for synthesizing atomically precise metal nanoclusters by applying disulfide, which is a widely available, stable, and environmentally friendly sulfur source. This method enables the construction of structurally diverse metal nanoclusters and especially features the synthesis of PhS-protected metal nanoclusters that were not easily achieved previously and the gram-scale synthesis. A reduction-oxidation cascade mechanism has been revealed for the photochemical route. This work is expected to open up new opportunities for metal nanocluster synthesis and will contribute to the practical applications of this kind of nanomaterial.

Immune-mediated necrotizing myopathy: Report of two cases.

BACKGROUND: Immune-mediated necrotizing myopathy is a rare autoimmune myopathy characterized by muscle weakness and elevated serum creatine kinase, with unique skeletal muscle pathology and magnetic resonance imaging features. CASE SUMMARY: In this paper, two patients are reported: One was positive for anti-signal recognition particle antibody, and the other was positive for anti-3-hydroxy-3-methylglutaryl coenzyme A reductase antibody. CONCLUSION: The clinical characteristics and treatment of the two patients were analysed, and the literature was reviewed to improve the recognition, diagnosis, and treatment of this disease.

Highly stretchable, tough and conductive chitin nanofiber composite hydrogel as a wearable sensor.

To meet the requirements of eco-friendly and sustainability in the 21st century, hydrogels based on biopolymer with conductivity and stretchable property have attained increasing attention for strain sensor. However, the as-prepared of hydrogel sensor with excellent mechanical property and high strain sensitivity is still a challenge. In this study, chitin nanofiber (ChNF) reinforced composite hydrogels of PACF are fabricated via a facile one-pot method. The obtained PACF composite hydrogel exhibits good transparency (80.6 % at 800 nm)and excellent mechanical properties (tensile strength, 261.2 kPa; tensile strain as high as 550.3 %). Moreover, the composite hydrogels also demonstrate excellent anti-compression performance. The composite hydrogels own good conductivity (1.20 S/m) and strain sensitivity. Most importantly, the hydrogel can be assembled as a strain/pressure sensor for detecting large-scale and small-scale human motion. Therefore, flexible conductive hydrogel strain sensors will have broad application prospects in artificial intelligence, electronic skin, and personal health.

Inhibitory Effect of Jinkui Shenqi Pills on Glucocorticoid-Enhanced Axial Length Elongation in Experimentally Myopic Guinea Pigs.

OBJECTIVE: To explore the underlying mechanism of inhibition by Jinkui Shenqi Pills (JKSQP) on glucocorticoid-enhanced axial length elongation in experimental lens-induced myopia (LIM) guinea pigs. METHODS: Sixty 2-week old male guinea pigs were randomly divided into 4 groups with 15 guinea pigs in each group, according to the random numbers generated by SPSS software: control, LIM, saline and JKSQP groups. The control group includes animals with no treatment, while the guinea pigs in the other 3 groups received lens-induced myopization on the right eyes throughout the experiment (for 8 weeks). The saline and JKSQP groups were given daily intraperitoneal injections of 10 mg/kg hydrocortisone for 2 consecutive weeks at the same time, and then orally administered either saline or JKSQP [13.5 g/(kg•d) for 6 consecutive weeks. Body weight, anal temperature and animal appearance were observed and recorded to evaluate the GC-associated symptoms. The ocular parameters, including refraction and axial length, were measured by streak retinoscopy and A-scan ultrasonography, respectively. The levels of plasma hormones associated with the hypothalamic-pituitary-adrenal axis (HPAA), including free triiodothyronine, free thyroxine, estradiol and testosterone, were measured by radioimmunoassay, and cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate were measured by enzyme-linked immunosorbent assay. In addition, the mRNA and protein expressions of retinal amphiregulin (AREG) was measured by quantitative real-time polymerase chain reaction and Western blotting, respectively. RESULTS: JKSQP effectively increased body weight and anal temperature, improved animal appearance and suppressed axial length elongation in glucocorticoid-enhanced myopic guinea pigs with normalization of 4 HPAA-associated plasma hormones (all P<0.05). The plasma level of cAMP was significantly increased, whereas the plasma level of cGMP and the mRNA and protein expressions of retinal AREG were decreased after treatment with JKSQP (all P<0.05). CONCLUSION: JKSQP exhibited a significant inhibitory effect on axial length elongation with decreased expression of AREG in the retina, and normalized 4 HPAA-associated plasma hormones and the expression of cAMP and cGMP in GC-enhanced myopic guinea pigs.

Ligand-enabled Ni-catalysed enantioconvergent intermolecular Alkyl-Alkyl cross-coupling between distinct Alkyl halides.

α-Tertiary aliphatic amides are key elements in organic molecules, which are abundantly present in natural products, pharmaceuticals, agrochemicals, and functional organic materials. Enantioconvergent alkyl-alkyl bond-forming process is one of the most straightforward and efficient, yet highly challenging ways to build such stereogenic carbon centers. Herein, we report an enantioselective alkyl-alkyl cross-coupling between two different alkyl electrophiles to access α-tertiary aliphatic amides. With a newly-developed chiral tridentate ligand, two distinct alkyl halides were successfully cross-coupled together to forge an alkyl-alkyl bond enantioselectively under reductive conditions. Mechanistic investigations reveal that one alkyl halides exclusively undergo oxidative addition with nickel versus in-situ formation of alkyl zinc reagents from the other alkyl halides, rendering formal reductive alkyl-alkyl cross-coupling from easily available alkyl electrophiles without preformation of organometallic reagents.

Bone marrow mesenchymal stem cell-derived exosomes miR-202-5p inhibited pyroptosis to alleviate lung ischemic-reperfusion injury by targeting CMPK2.

Bone mesenchymal stem cell-derived exosome (BMSC-exosome) is a potential candidate for lung ischemia-reperfusion injury (LIRI) treatment. This study aims to investigate the anti-pyroptosis effect of BMSC-exosomes in LIRI. The LIRI cell model was established by hypoxia/reoxygenation (H/R) treatment. Interleukin (IL)-1ß and IL-18 levels were examined by enzyme-linked immunosorbent assay. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Lactate dehydrogenase (LDH) release was examined using a LDH assay kit. The interaction between microRNA (miR)-202-5p and cytidine monophosphate kinase 2 (CMPK2) was analyzed using dual-luciferase reporter assay and RNA immunoprecipitation. BMSC-exosomes promoted cell viability and suppressed pyroptosis in H/R-treated mouse lung epithelial. miR-202-5p was enriched in BMSC-exosomes, and exosomal miR-202-5p inhibition upregulated pyroptosis-associated proteins, including cleaved N-terminal Gasdermin D, nucleotide-binding domain-like receptor family member pyrin domain-containing protein 3, and Caspase1. Meanwhile, miR-202-5p suppressed CMPK2 expression by directly targeting CMPK2. Expectedly, CMPK2 knockdown reversed the promoting effect of exosomal miR-202-5p inhibition on pyroptosis in LIRI. Therefore, BMSC-derived exosome miR-202-5p repressed pyroptosis to inhibit LIRI progression by targeting CMPK2.

Intravitreal injection of fibrillin 2 (Fbn2) recombinant protein for therapy of retinopathy in a retina-specific Fbn2 knock-down mouse model.

Mutations in the extracellular matrix gene Fibrillin-2 (FBN2) are related to genetic macular degenerative disorders including age-related macular degeneration (AMD) and early-onset macular degeneration (EOMD). It was reported that the retinal protein expression of FBN2 was reduced in patients with AMD and EOMD. The effect of exogenously supplied fbn2 recombinant protein on fbn2-deficiency-related retinopathy was not known. Here we investigated the efficacy and molecular mechanism of intravitreally applied fibrin-2 recombinant protein in mice with fbn2-deficient retinopathy. The experimental study included groups (all n = 9) of adult C57BL/6J male mice which underwent no intervention, intravitreal injection of adeno-associated virus (AAV) empty vector or intravitreal injection of AAV-sh-fbn2 (adeno-associated virus for expressing short hairpin RNA for fibrillin-2) followed by three intravitreal injections of fbn2 recombinant protein, given in intervals of 8 days in doses of 0.30 µg, 0.75 µg, 1.50 µg, and 3.00 µg, respectively. Eyes with intravitreally applied AAV-sh-fbn2 as compared to eyes with injection of AAV-empty vector or developed an exudative retinopathy with involvement of the deep retinal layers, reduction in axial length and reduction in ERG amplitudes. After additional and repeated application of fbn2 recombinant protein, the retinopathy improved with an increase in retinal thickness and ERG amplitude, the mRNA and protein expression of transforming growth factor-beta (TGF-ß1) and TGF-ß binding protein (LTBP-1) increased, and axial length elongated, with the difference most marked for the dose of 0.75 µg of fbn2 recombinant protein. The observations suggest that intravitreally applied fbn2 recombinant protein reversed the retinopathy caused by an fbn2 knockdown.

Photo-activated autophagy-associated tumour cell death by lysosome impairment based on manganese-doped graphene quantum dots.

Autophagy is indispensable in normal cellular processes, yet detrimental to cancer treatment because it severely lowers the therapeutic efficiency. One of the keys to solve this problem may lie in lysosomes, which requires the rational design of nanomedicine that is capable of localizing and maintaining its efficacy in lysosomes. In this work, a facile and versatile nanoplatform based on manganese-doped graphene quantum dots (Mn-FGQDs) is developed for effective and precise photodynamic impairment of lysosomes. Specifically, the incorporation of Mn not only strengthens the generation capability of reactive oxygen species (ROS), but also facilitates its accumulation in lysosomes. Moreover, Mn-FGQDs are structurally robust and retain their high photodynamic efficiency in the lysosomal environment. On this basis, the light-triggered generation of ROS would primarily influence the function of lysosomes, leading to lysosome impairment and thereby effectively blocking the protective autophagy recycling. More impressively, a continuous increase in the oxidative stress level in lysosomes causes severe autophagy dysfunction, as revealed from an abnormal increase in autophagosomes and autolysosomes. This eventually results in autophagy-associated cancer cell death accompanied by the characteristics of apoptosis and ferroptosis. Overall, the present work paves a new way for cancer therapy via precise lysosome impairment induced autophagy dysfunction.