Dicarbofunctionalization of Vinylarenes with Pyridine and Aldehydes via Photocatalytic Hydrogen Atom Transfer.

We describe a metal-free and mild three-component reaction utilizing vinylarenes, alkyl aldehydes, and 4-cyanopyridine. In this reaction, the scope of vinylarenes and alkyl aldehydes includes over 40 examples, generating a variety of ß-pyridinyl ketones. Moreover, potential applications of this method have been demonstrated by the functionalization of pharmaceutical molecules. An acyl radical is proposed to be produced via a polarity-matched hydrogen atom transfer between alkyl aldehydes and a triplet-state diradical from benzophenone.

Novel electrochemical process for recycling of valuable metals from spent lithium-ion batteries.

Effective recovery of Li, Co, Ni and Mn from cathode materials of spent lithium-ion batteries (LIBs) has become a global concern. In this study, electrolysis of copper sulfate to produce sulfuric acid and electrons were utilized to recover Li, Co, Ni and Mn from spent LIBs. The obtained results showed that 93 % of Ni, 91 % of Co, 89 % of Mn and 94 % of Li were leached and 99 % of Cu was deposited during leaching process by adopting the 0.225 mol/L of copper sulfate with a solid/liquid ratio of 15 g/L at a current density of 50 mA/m2 and 80 °C for 4.5 h. Then, a current efficiency of 72 % for the cathode and 30 % for the anode was achieved at a current density of 40 mA/m2, 70 °C and pH 2.5 during electrodeposition process. The Ni-Co deposition followed the principle of anomalous codeposition and the complete deposition time of Co, Ni and Mn were 3 h, 9 h and 10 h, respectively. Eventually, the Ni, Co, Mn, Li and Cu can be recovered as Ni-Co alloy, MnO2 and Li2CO3 and Cu metals with the corresponding recovery rates of 99.40 %, 91.00 %, 90.68 %, 85.59 % and 89.55 %, respectively. This study proposes a promising strategy for recycling cathode materials from spent LIBs without addition of chemical reductants and acids.

Caloric restriction leading to attenuation of experimental Alzheimer's disease results from alterations in gut microbiome.

BACKGROUND: Caloric restriction (CR) might be effective for alleviating/preventing Alzheimer's disease (AD), but the biological mechanisms remain unclear. In the current study, we explored whether CR caused an alteration of gut microbiome and resulted in the attenuation of cognitive impairment of AD animal model. METHODS: Thirty-week-old male APP/PS1 transgenic mice were used as AD models (AD mouse). CR was achieved by 30% reduction of daily free feeding (ad libitum, AL) amount. The mice were fed with CR protocol or AL protocol for six consecutive weeks. RESULTS: We found that with CR treatment, AD mice showed improved ability of learning and spatial memory, and lower levels of Aß40, Aß42, IL-1ß, TNF-α, and ROS in the brain. By sequencing 16S rDNA, we found that CR treatment resulted in significant diversity in composition and abundance of gut flora. At the phylum level, Deferribacteres (0.04%), Patescibacteria (0.14%), Tenericutes (0.03%), and Verrucomicrobia (0.5%) were significantly decreased in CR-treated AD mice; at the genus level, Dubosiella (10.04%), Faecalibaculum (0.04%), and Coriobacteriaceae UCG-002 (0.01%) were significantly increased in CR-treated AD mice by comparing with AL diet. CONCLUSIONS: Our results demonstrate that the attenuation of AD following CR treatment in APP/PS1 mice may result from alterations in the gut microbiome. Thus, gut flora could be a new target for AD prevention and therapy.

Recent advances in cell membrane camouflaged nanotherapeutics for the treatment of bacterial infection.

Infectious diseases caused by bacterial infections are common in clinical practice. Cell membrane coating nanotechnology represents a pioneering approach for the delivery of therapeutic agents without being cleared by the immune system in the meantime. And the mechanism of infection treatment should be divided into two parts: suppression of pathogenic bacteria and suppression of excessive immune response. The membrane-coated nanoparticles exert anti-bacterial function by neutralizing exotoxins and endotoxins, and some other bacterial proteins. Inflammation, the second procedure of bacterial infection, can also be suppressed through targeting the inflamed site, neutralization of toxins, and the suppression of pro-inflammatory cytokines. And platelet membrane can affect the complement process to suppress inflammation. Membrane-coated nanoparticles treat bacterial infections through the combined action of membranes and nanoparticles, and diagnose by imaging, forming a theranostic system. Several strategies have been discovered to enhance the anti-bacterial/anti-inflammatory capability, such as synthesizing the material through electroporation, pretreating with the corresponding pathogen, membrane hybridization, or incorporating with genetic modification, lipid insertion, and click chemistry. Here we aim to provide a comprehensive overview of the current knowledge regarding the application of membrane-coated nanoparticles in preventing bacterial infections as well as addressing existing uncertainties and misconceptions.

Metal Free Functionalization of Saturated Heterocycles with Vinylarenes and Pyridine Enabled by Photocatalytic Hydrogen Atom Transfer.

Saturated heterocycles are important class of structural scaffolds in small-molecule drugs, natural products, and synthetic intermediates. Here, we disclosed a metal free, mild, and scalable functionalization of saturated heterocycles using vinylarenes as a linchpin approach. Key to success of this transformation is the employing of simple and cheap benzophenone as a hydrogen atom transfer (HAT) catalyst. This operationally robust process was used for the making of diverse functionalized saturated heterocycles. Furthermore, aldehydes, alkane, and alcohol have been functionalized under the optimized conditions. The potential pharmaceutical utility of the procedure has also been demonstrated by late-stage functionalization of bioactive natural compounds and pharmaceutical molecules. Initial mechanism studies and control experiments were performed to elucidate the mechanism of the reactions.

Flexible silicon solar cells with high power-to-weight ratios.

Silicon solar cells are a mainstay of commercialized photovoltaics, and further improving the power conversion efficiency of large-area and flexible cells remains an important research objective1,2. Here we report a combined approach to improving the power conversion efficiency of silicon heterojunction solar cells, while at the same time rendering them flexible. We use low-damage continuous-plasma chemical vapour deposition to prevent epitaxy, self-restoring nanocrystalline sowing and vertical growth to develop doped contacts, and contact-free laser transfer printing to deposit low-shading grid lines. High-performance cells of various thicknesses (55-130 µm) are fabricated, with certified efficiencies of 26.06% (57 µm), 26.19% (74 µm), 26.50% (84 µm), 26.56% (106 µm) and 26.81% (125 µm). The wafer thinning not only lowers the weight and cost, but also facilitates the charge migration and separation. It is found that the 57-µm flexible and thin solar cell shows the highest power-to-weight ratio (1.9 W g-1) and open-circuit voltage (761 mV) compared to the thick ones. All of the solar cells characterized have an area of 274.4 cm2, and the cell components ensure reliability in potential-induced degradation and light-induced degradation ageing tests. This technological progress provides a practical basis for the commercialization of flexible, lightweight, low-cost and highly efficient solar cells, and the ability to bend or roll up crystalline silicon solar cells for travel is anticipated.

Hydration deactivation mechanism of the 〈100〉 oriented cuprous oxide photocathodes in solar water splitting and the regenerated three-dimensional structure.

Photocorrosion is the most ticklish problem of cuprous oxide (Cu2O), and it is widely assumed that the deactivation of Cu2O photocathodes in solar water splitting is caused by spontaneous oxidation-reduction (REDOX) reactions. However, this work shows that 〈100〉-oriented Cu2O photocathodes undergo a non-REDOX hydration deactivation mechanism. Briefly, water molecules are embedded in the Cu2O crystals at low potential under illumination and produce amorphous CuOH, which can be dehydrated at high potential to heal the Cu-O-Cu bonds and regenerate foamed Cu2O films with a three-dimensional skeleton structure. This study provides a new insight towards the protection and application of Cu2O photocathodes.

Activation of Aryl and Alkyl Halides Enabled by Strong Photoreduction Potentials of a Hantzsch Ester/Cs2CO3 System.

We disclose herein a light-induced Hantzsch ester-initiated aryl and alkyl radical generation protocol from aryl halides (Br and Cl) and alkyl iodides. This method provides access to a wide range of benzo-fused heterocycles and C(sp3)-C(sp3) coupling products. The reductive detosylation reaction has also been demonstrated using the same reaction conditions. Initial mechanism studies provide evidence of the formation of an alkyl radical.

Coordinating activation strategy enables 1,2-alkylamidation of alkynes.

The radical 1,2-difunctionalization reaction of alkynes has been evolved into a versatile approach for expeditiously increasing the complexity of the common feedstock alkyne. However, intermolecular 1,2-carboamidation with general alkyl groups is an unsolved problem. Herein, we show that a coordinating activation strategy could act as an efficient tool for enabling radical 1,2-alkylamidation of alkynes. With the employment of diacyl peroxides as both alkylating reagents and internal oxidants, a large library of ß-alkylated enamides is constructed in a three-component manner from readily accessible amides and alkynes. This protocol exhibits broad substrate scope with good functional group compatibility and is amenable for late-stage functionalization of natural molecules and biologically compounds.

Realizing the Ultralow Lattice Thermal Conductivity of Cu3SbSe4 Compound via Sulfur Alloying Effect.

Cu3SbSe4 is a potential p-type thermoelectric material, distinguished by its earth-abundant, inexpensive, innocuous, and environmentally friendly components. Nonetheless, the thermoelectric performance is poor and remains subpar. Herein, the electrical and thermal transport properties of Cu3SbSe4 were synergistically optimized by S alloying. Firstly, S alloying widened the band gap, effectively alleviating the bipolar effect. Additionally, the substitution of S in the lattice significantly increased the carrier effective mass, leading to a large Seebeck coefficient of ~730 µVK-1. Moreover, S alloying yielded point defect and Umklapp scattering to significantly depress the lattice thermal conductivity, and thus brought about an ultralow κlat ~0.50 Wm-1K-1 at 673 K in the solid solution. Consequently, multiple effects induced by S alloying enhanced the thermoelectric performance of the Cu3SbSe4-Cu3SbS4 solid solution, resulting in a maximum ZT value of ~0.72 at 673 K for the Cu3SbSe2.8S1.2 sample, which was ~44% higher than that of pristine Cu3SbSe4. This work offers direction on improving the comprehensive TE in solid solutions via elemental alloying.

Insight into the Mechanisms of Nitride Films with Excellent Hardness and Lubricating Performance: A Review.

Transition metal nitride (TMN) films with excellent hardness and lubricating performance are versatile low dimension materials, which are widely used in various fields including industries, transportation, aerospace, and so on. This paper introduces one film design strategy and provides a review of the mechanisms for strengthening and lubricating nitride films. The design strategy refers to two aspects which determine the structures, the performance, the components, and the chemical constitutions of nitride films The strengthening mechanisms of nitride films are then illuminated in detail, including the solid solution effect, the grain size effect, the secondary phase effect, the stress or stress field effect, the template effect, and the valence electron concentration effect. Five lubricating mechanisms are next summarized, including the easy-shear nature, the tribo-chemical reactions, the lubricious fluorides, the textured contact surface, and the synergistic effect. This paper aims to give a comprehensive introduction for understanding the mechanisms of strengthening and lubrication of nitride films for students and researchers, as well as to understand the current research progress in nitride films for exploring research gaps.

Super-Macroporous Lightweight Materials Templated from Bicontinuous Intra-Phase Jammed Emulsion Gels Based on Nanochitin.

Non-equilibrium multiphase systems are formed by mixing two immiscible nanoparticle dispersions, leading to bicontinuous emulsions that template cryogels with interconnected, tortuous channels. Herein, a renewable, rod-like biocolloid (chitin nanocrystals, ChNC) is used to kinetically arrest bicontinuous morphologies. Specifically, it is found that ChNC stabilizes intra-phase jammed bicontinuous systems at an ultra-low particle concentration (as low as 0.6 wt.%), leading to tailorable morphologies. The synergistic effects of ChNC high aspect ratio, intrinsic stiffness, and interparticle interactions produce hydrogelation and, upon drying, lead to open channels bearing dual characteristic sizes, suitably integrated into robust bicontinuous ultra-lightweight solids. Overall, it demonstrates the successful formation of ChNC-jammed bicontinuous emulsions and a facile emulsion templating route to synthesize chitin cryogels that form unique super-macroporous networks.

Microneedle-Mediated Transcutaneous Immunization: Potential in Nucleic Acid Vaccination.

Efforts aimed at exploring economical and efficient vaccination have taken center stage to combat frequent epidemics worldwide. Various vaccines have been developed for infectious diseases, among which nucleic acid vaccines have attracted much attention from researchers due to their design flexibility and wide application. However, the lack of an efficient delivery system considerably limits the clinical translation of nucleic acid vaccines. As mass vaccinations via syringes are limited by low patient compliance and high costs, microneedles (MNs), which can achieve painless, cost-effective, and efficient drug delivery, can provide an ideal vaccination strategy. The MNs can break through the stratum corneum barrier in the skin and deliver vaccines to the immune cell-rich epidermis and dermis. In addition, the feasibility of MN-mediated vaccination is demonstrated in both preclinical and clinical studies and has tremendous potential for the delivery of nucleic acid vaccines. In this work, the current status of research on MN vaccines is reviewed. Moreover, the improvements of MN-mediated nucleic acid vaccination are summarized and the challenges of its clinical translation in the future are discussed.

MicroRNA-196-5p targets Derlin-1 to induce autophagy in human osteosarcoma cells.

Osteosarcoma is a highly prevalent type of primary bone tissues in children and young adolescents. Micro-RNA (miR) dysregulation has been linked to osteosarcoma tumorigenesis. The role of miR-196-5p was investigated in modulating the growth and metastatic behaviour of human osteosarcoma cells, along with exploring its mechanism of action. As shown by RT-qPCR expression analysis, osteosarcoma cell lines exhibited prominent (P<0.05) transcriptional repression of miR-196-5p. The latter was thus transiently overexpressed in osteosarcoma cells, which resulted in the loss of cell viability and colony formation via induction of autophagy. The western blot analysis of the autophagy marker proteins revealed that the expression of Beclin 1 and LC3B II proteins was induced by miR-196-5p, whereas that of p62 and LC3BI was repressed. Moreover, osteosarcoma cells overexpressing miR-196-5p showed significantly (P<0.05) lower migration and invasion concerning the control osteosarcoma cells. According to the results of the in-silico analysis, Derlin-1 participates in the regulation of miR-196-5p in osteosarcoma, and this prediction has been validated using a dual luciferase assay. The results indicated that miR-196-5p exerted its molecular role by targeting Derlin-1 at the post-transcriptional level. Summing up, the study revealed the modulatory potential of miR-196-5p/Derlin-1 on osteosarcoma cells and provided insights into the possible implications for the treatment and prognosis of the disease.

Acoustic metamaterials-driven transdermal drug delivery for rapid and on-demand management of acute disease.

Transdermal drug delivery provides convenient and pain-free self-administration for personalized therapy. However, challenges remain in treating acute diseases mainly due to their inability to timely administrate therapeutics and precisely regulate pharmacokinetics within a short time window. Here we report the development of active acoustic metamaterials-driven transdermal drug delivery for rapid and on-demand acute disease management. Through the integration of active acoustic metamaterials, a compact therapeutic patch is integrated for penetration of skin stratum corneum and active percutaneous transport of therapeutics with precise control of dose and rate over time. Moreover, the patch device quantitatively regulates the dosage and release kinetics of therapeutics and achieves better delivery performance in vivo than through subcutaneous injection. As a proof-of-concept application, we show our method can reverse life-threatening acute allergic reactions in a female mouse model of anaphylaxis via a multi-burst delivery of epinephrine, showing better efficacy than a fixed dosage injection of epinephrine, which is the current gold standard 'self-injectable epinephrine' strategy. This innovative method may provide a promising means to manage acute disease for personalized medicine.

Efficient Electrocatalyst Nanoparticles from Upcycled Class II Capacitors.

To move away from fossil fuels, the electrochemical reaction plays a critical role in renewable energy sources and devices. The anodic oxygen evolution reaction (OER) is always coupled with these reactions in devices but suffers from large energy barriers. Thus, it is important for developing efficient OER catalysts with low overpotential. On the other hand, there are large amounts of metals in electronic waste (E-waste), especially various transition metals that are promising alternatives for catalyzing OER. Hence, this work, which focuses on upcycling Class II BaTiO3 Multilayer Ceramic Capacitors, of which two trillion were produced in 2011 alone. We achieved this by first using a green solvent extraction method that combined the ionic liquid Aliquat® 336 and hydrochloride acid to recover a mixed solution of Ni, Fe and Cu cations, and then using such a solution to synthesize high potential catalysts NiFe hydroxide and NiCu hydroxide for OER. NiFe-hydroxide has been demonstrated to have faster OER kinetics than the NiCu-hydroxide and commercial c-RuO2. In addition, it showed promising results after the chronopotentiometry tests that outperform c-RuO2.

Methylation-mediated silencing of PTPRD induces pulmonary hypertension by promoting pulmonary arterial smooth muscle cell migration via the PDGFRB/PLCγ1 axis.

OBJECTIVE: Pulmonary hypertension is a lethal disease characterized by pulmonary vascular remodeling and is mediated by abnormal proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs). Platelet-derived growth factor BB (PDGF-BB) is the most potent mitogen for PASMCs and is involved in vascular remodeling in pulmonary hypertension development. Therefore, the objective of our study is to identify novel mechanisms underlying vascular remodeling in pulmonary hypertension. METHODS: We explored the effects and mechanisms of PTPRD downregulation in PASMCs and PTPRD knockdown rats in pulmonary hypertension induced by hypoxia. RESULTS: We demonstrated that PTPRD is dramatically downregulated in PDGF-BB-treated PASMCs, pulmonary arteries from pulmonary hypertension rats, and blood and pulmonary arteries from lung specimens of patients with hypoxic pulmonary arterial hypertension (HPAH) and idiopathic PAH (iPAH). Subsequently, we found that PTPRD was downregulated by promoter methylation via DNMT1. Moreover, we found that PTPRD knockdown altered cell morphology and migration in PASMCs via modulating focal adhesion and cell cytoskeleton. We have demonstrated that the increase in cell migration is mediated by the PDGFRB/PLCγ1 pathway. Furthermore, under hypoxic condition, we observed significant pulmonary arterial remodeling and exacerbation of pulmonary hypertension in heterozygous PTPRD knock-out rats compared with the wild-type group. We also demonstrated that HET group treated with chronic hypoxia have higher expression and activity of PLCγ1 in the pulmonary arteries compared with wild-type group. CONCLUSION: We propose that PTPRD likely plays an important role in the process of pulmonary vascular remodeling and development of pulmonary hypertension in vivo .

MicroRNAs in Pulmonary Hypertension, from Pathogenesis to Diagnosis and Treatment.

Pulmonary hypertension (PH) is a fatal and untreatable disease, ultimately leading to right heart failure and eventually death. microRNAs are small, non-coding endogenous RNA molecules that can regulate gene expression and influence various biological processes. Changes in microRNA expression levels contribute to various cardiovascular disorders, and microRNAs have been shown to play a critical role in PH pathogenesis. In recent years, numerous studies have explored the role of microRNAs in PH, focusing on the expression profiles of microRNAs and their signaling pathways in pulmonary artery smooth muscle cells (PASMCs) or pulmonary artery endothelial cells (PAECs), PH models, and PH patients. Moreover, certain microRNAs, such as miR-150 and miR-26a, have been identified as good candidates of diagnosis biomarkers for PH. However, there are still several challenges for microRNAs as biomarkers, including difficulty in normalization, specificity in PH, and a lack of longitudinal and big sample-sized studies. Furthermore, microRNA target drugs are potential therapeutic agents for PH treatment, which have been demonstrated in PH models and in humans. Nonetheless, synthetic microRNA mimics or antagonists are susceptible to several common defects, such as low drug efficacy, inefficient drug delivery, potential toxicity and especially, off-target effects. Therefore, finding clinically safe and effective microRNA drugs remains a great challenge, and further breakthrough is urgently needed.

Detection of Lower Body for AGV Based on SSD Algorithm with ResNet.

Detection of human lower body provides an implementation idea for the automatic tracking and accurate relocation of automatic vehicles. Based on traditional SSD and ResNet, this paper proposes an improved detection algorithm R-SSD for human lower body detection, which utilizes ResNet50 instead of VGG16 to improve the feature extraction level of the model. According to the application of acquisition equipment, the model input resolution is increased to 448 × 448 and the model detection range is expanded. Six feature maps of the updated resolution network are selected for detection and the lower body image dataset is clustered into five categories for aspect ratio, which are evenly distributed to each feature detection map. The experimental results show that the model R-SSD detection accuracy after training reaches 85.1% mAP. Compared with the original SSD, the detection accuracy is improved by 7% mAP. The detection confidence in practical application reaches more than 99%, which lays the foundation for subsequent tracking and relocation for automatic vehicles.