Hybrid Dynamic Covalent Network-Based Protecting Layer for Stable Li-Metal Batteries.

Metallic lithium (Li) is considered as the "Holy Grail" anode material for next-generation energy storage systems due to its extremely high theoretical capacity and low electrochemical potential. Before the commercialization of the Li electrode, dendritic Li growth and the unstable solid electrolyte interphase layer should be conquered. Herein, a hybrid covalent adaptable polymer network (HCAPN) is prepared via the random copolymerization of poly(ethylene glycol) methyl ether methacrylate and -acetoacetoxyethyl methacrylate, followed by chemical cross-linking with polyethylenimine (PEI) and amine-modified silicon dioxide (SiO2). Such a hybrid network, where PEI and amine-modified SiO2 formed a vinylogous urethane-based dynamic covalent bond with the copolymer, respectively, shows improved mechanical properties, solvent resistance, and excellent healability/recyclability. As the protecting layer on the Li electrode, the assembled HCAPN@Li||HCAPN@Li symmetric cell shows a long cycle life of 800 h with low overpotential at a current density of 1 mA cm-2, and superior electrochemical performance can be achieved in the HCAPN@Li||LiFePO4 full cell (capacity retention of 77% over 400 cycles at 1.5 C) and HCAPN@Li||NCM811 cell (capacity retention of 79% after 300 cycles). Surface morphology analysis is also performed for physical insight into their role as protecting layer. This work provides a new perspective for constructing a hybrid dynamic covalent network-based polymer protecting layer for inhibiting Li dendrite growth.

Hybrid Dynamic Covalent Network as a Protective Layer and Solid-State Electrolyte for Stable Lithium-Metal Batteries.

Lithium (Li) metal is a highly promising anode material for next-generation high-energy-density batteries, while Li dendrite growth and the unstable solid electrolyte interphase layer inhibit its commercialization. Herein, a chemically grafted hybrid dynamic network (CHDN) is rationally designed and synthesized by the 4,4'-thiobisbenzenamine cross-linked poly(poly(ethylene glycol) methyl ether methacrylate-r-glycidyl methacrylate) and (3-glycidyloxypropyl) trimethoxysilane-functionalized SiO2 nanoparticles, which is utilized as a protective layer and hybrid solid-state electrolyte (HSE) for stable Li-metal batteries. The presence of a dynamic exchangeable disulfide affords self-heability and recyclability, and the chemical attachment between SiO2 nanoparticles and the polymer matrix enables the homogeneous distribution of inorganic fillers and mechanical robustness. With integrated flexibility, fast segmental dynamics, and autonomous adaptability, the as-prepared CHDN-based protective layer enables superior electrochemical performance in half cells and full cells (capacity retention of 83.7% over 400 cycles for the CHDN@Li/LiFePO4 cell at 1 C). Furthermore, benefiting from intimate electrode/electrolyte interfacial contact, CHDN-based solid-state cells deliver excellent electrochemical performance (capacity retention of 89.5% over 500 cycles for the Li/HSE/LiFePO4 cell at 0.5 C). In addition, the Li/HSE/LiFePO4 pouch cell exhibits superior safety, even exposing various physical damage conditions. This work thereby provides a fresh insight into a rational design principle for dynamic network-based protective layers and solid-state electrolytes for battery applications.

Genetic Diversity Analysis of Sapindus in China and Extraction of a Core Germplasm Collection Using EST-SSR Markers.

Sapindus is an important forest tree genus with utilization in biodiesel, biomedicine, and it harbors great potential for biochemical engineering applications. For advanced breeding of Sapindus, it is necessary to evaluate the genetic diversity and construct a rationally designed core germplasm collection. In this study, the genetic diversity and population structure of Sapindus were conducted with 18 expressed sequence tag-simple sequence repeat (EST-SSR) markers in order to establish a core germplasm collection from 161 Sapindus accessions. The population of Sapindus showed high genetic diversity and significant population structure. Interspecific genetic variation was significantly higher than intraspecific variation in the Sapindus mukorossi, Sapindus delavayi, and combined Sapindus rarak plus Sapindus rarak var. velutinus populations. S. mukorossi had abundant genetic variation and showed a specific pattern of geographical variation, whereas S. delavayi, S. rarak, and S. rarak var. velutinus showed less intraspecific variation. A core germplasm collection was created that contained 40% of genetic variation in the initial population, comprising 53 S. mukorossi and nine S. delavayi lineages, as well as single representatives of S. rarak and S. rarak var. velutinus. These results provide a germplasm basis and theoretical rationale for the efficient management, conservation, and utilization of Sapindus, as well as genetic resources for joint genomics research in the future.

Metabolome and Transcriptome Analysis Reveals the Transcriptional Regulatory Mechanism of Triterpenoid Saponin Biosynthesis in Soapberry (Sapindus mukorossi Gaertn.).

Soapberry (Sapindus mukorossi Gaertn.) pericarps are rich in valuable bioactive triterpenoid saponins. However, the saponin content dynamics and the molecular regulatory network of saponin biosynthesis in soapberry pericarps remain largely unclear. Here, we performed combined metabolite profiling and transcriptome analysis to identify saponin accumulation kinetic patterns, investigate gene networks, and characterize key candidate genes and transcription factors (TFs) involved in saponin biosynthesis in soapberry pericarps. A total of 54 saponins were tentatively identified, including 25 that were differentially accumulated. Furthermore, 49 genes putatively involved in sapogenin backbone biosynthesis and some candidate genes assumed to be responsible for the backbone modification, including 41 cytochrome P450s and 45 glycosyltransferases, were identified. Saponin-specific clusters/modules were identified by Mfuzz clustering and weighted gene coexpression network analysis, and one TF-gene regulatory network underlying saponin biosynthesis was proposed. The results of yeast one-hybrid assay and electrophoretic mobility shift assay suggested that SmbHLH2, SmTCP4, and SmWRKY27 may play important roles in the triterpenoid saponin biosynthesis by directly regulating the transcription of SmCYP71D-3 in the soapberry pericarp. Overall, these findings provide valuable information for understanding the molecular regulatory mechanism of saponin biosynthesis, enriching the gene resources, and guiding further research on triterpenoid saponin accumulation in soapberry pericarps.

Self-Healable, Highly Stretchable, Ionic Conducting Polymers as Efficient Protecting Layers for Stable Lithium-Metal Electrodes.

Although numerous studies on polymeric protective films to stabilize lithium (Li)-metal electrodes have been reported, the construction of self-healing polymers that enables the long-term operation of Li-metal batteries (LMBs) at relatively low temperatures has rarely been demonstrated. Herein, a highly stretchable, autonomous self-healable, and ionic-conducting polymer network (SHIPN) is synthesized as an efficient protective film for LMBs. The network backbone, synthesized from copolymerization of poly(ethylene glycol)-mono-methacrylate (PEGMMA) and 2-[[(butylamino)carbonyl]oxy]ethyl acrylate (BCOE), is chemically cross-linked via diisocyanate. With SHIPN-modified electrodes, enhanced electrochemical performance can be achieved in Li/Cu, Li/Li, and Li/LiFePO4 (Li/LFP) cells. The SHIPN@Li/LFP cell delivers a capacity retention of 85.6% after 500 cycles at 5 °C, resulting from the low-temperature self-healability of SHIPN. In full cells with a high-mass-loading LFP cathode (∼17 mg cm-2), the capacity retention is at least 300% higher than that with a bare Li electrode. Further physical characterizations of electrodes confirm the effect of SHIPN in enhancing the interfacial stability and suppressing Li dendrite growth. Our results will provide insights into rationally designing soft and hybrid materials toward stable LMBs at different temperatures.

Integrative analysis of microRNAs and mRNAs reveals the regulatory networks of triterpenoid saponin metabolism in Soapberry (Sapindus mukorossi Gaertn.).

Triterpenoid saponin are important secondary metabolites and bioactive constituents of soapberry (Sapindus mukorossi Gaertn.) and are widely used in medicine and toiletry products. However, little is known about the roles of miRNAs in the regulation of triterpenoid saponin biosynthesis in soapberry. In this study, a total of 3036 miRNAs were identified, of which 1372 miRNAs were differentially expressed at different stages of pericarp development. Important KEGG pathways, such as terpenoid backbone biosynthesis, sesquiterpenoid and triterpenoid biosynthesis, and basal transcription factors were highlighted, as well the roles of some key miRNAs, such as ath-miR5021, han-miR3630-3p, and ppe-miR858, which may play important roles in regulating triterpenoid saponin biosynthesis. In addition, 58 miRNAs might participate in saponin biosynthesis pathways by predicting the targets of those miRNAs to 53 saponin biosynthesis structural genes. And 75 miRNAs were identified to potentially play vital role in saponin accumulation by targeting transcript factor genes, bHLH, bZIP, ERF, MYB, and WRKY, respectively, which are candidate regulatory genes in the pathway of saponin biosynthesis. The results of weighted gene coexpression network analysis (WGCNA) suggested that two saponin-specific miRNA modules and 10 hub miRNAs may participate in saponin biosynthesis. Furthermore, multiple miRNA-mRNA regulatory networks potentially involved in saponin biosynthesis were generated, e.g., ath-miR5021-SmIDI2/SmGPS5/SmbAS1/SmCYP71D-3/SmUGT74G-2, han-miR3630-3p-SmCYP71A-14/SmbHLH54/SmMYB135/SmWRKY32, and ppe-miR858-SmMYB5/SmMYB32. qRT-PCR analysis validated the expression patterns of nine miRNAs and 12 corresponding target genes. This study represents the first comprehensive analysis of miRNAs in soapberry and lays the foundation for further understanding of miRNA-based regulation in triterpenoid saponin biosynthesis.

Metabolomics analysis of the soapberry (Sapindus mukorossi Gaertn.) pericarp during fruit development and ripening based on UHPLC-HRMS.

Soapberry (Sapindus mukorossi Gaertn.) is a multi-functional tree with widespread application in toiletries, biomedicine, biomass energy, and landscaping. The pericarp of soapberry can be used as a medicine or detergent. However, there is currently no systematic study on the chemical constituents of soapberry pericarp during fruit development and ripening, and the dynamic changes in these constituents still unclear. In this study, a non-targeted metabolomics approach using ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) was used to comprehensively profile the variations in metabolites in the soapberry pericarp at eight fruit growth stages. The metabolome coverage of UHPLC-HRMS on a HILIC column was higher than that of a C18 column. A total of 111 metabolites were putatively annotated. Principal component analysis and hierarchical clustering analysis of pericarp metabolic composition revealed clear metabolic shifts from early (S1-S2) to late (S3-S5) development stages to fruit ripening stages (S6-S8). Furthermore, pairwise comparison identified 57 differential metabolites that were involved in 18 KEGG pathways. Early fruit development stages (S1-S2) were characterized by high levels of key fatty acids, nucleotides, organic acids, and phosphorylated intermediates, whereas fruit ripening stages (S6-S8) were characterized by high contents of bioactive and valuable metabolites, such as troxipide, vorinostat, furamizole, alpha-tocopherol quinone, luteolin, and sucrose. S8 (fully developed and mature stage) was the most suitable stage for fruit harvesting to utilize the pericarp. To the best of our knowledge, this was the first metabolomics study of the soapberry pericarp during whole fruit growth. The results could offer valuable information for harvesting, processing, and application of soapberry pericarp, as well as highlight the metabolites that could mediate the biological activity or properties of this medicinal plant.

Gene-modified Exosomes Protect the Brain Against Prolonged Deep Hypothermic Circulatory Arrest.

BACKGROUND: Neurologic deficit remains a major complication after cardiovascular surgeries with deep hypothermic circulatory arrest (DHCA). We hypothesized that exosomes derived from bone marrow mesenchymal stem cells (MSCs) may conduct cerebral protection against prolonged DHCA in rats, and overexpressing microRNA-214 (miR-214) may further enhance the neuroprotection. METHODS: Cultured MSCs were transfected with lentivirus vectors containing pre-miR-214 or control vectors. Exosomes were isolated by centrifugation. The DHCA was conducted for 60 minutes when the pericranial temperature was cooled to 18°C. Exosomes from MSCs, MSCs transfected with control vectors, or pre-miR-214 were administered by intracerebroventricular injection 1 day before DHCA. RESULTS: Transfection of pre-miR-214 significantly enhanced the miR-214 expression in exosomes from MSCs. All exosome-pretreating groups exhibited lower levels of interleukin-1ß and tumor necrosis factor-α, higher capillary density, more significant neurogenesis and angiogenesis, and more normal neurons in the hippocampus than those of the control group. Exosome pretreatment markedly improved the spatial learning and memory function and vestibulomotor function. Compared with exosomes from MSCs or MSCs transfected with control vectors, miR-214-enriched exosomes remarkably enhanced the miR-214 level and expressions of phosphor-protein kinase B and Bcl-2, inhibited expressions of phosphate and tension homology, Bcl-2 interacting mediator of cell death, Bcl-2-associated X protein, and cleaved Caspase-3, and increased the number of survival neurons. Significantly better neurologic functions were also detected in rats pretreated with miR-214-enriched exosomes. CONCLUSIONS: Exosomes from MSCs conduct powerful neuroprotection against cerebral injury induced by DHCA, which can be further enhanced by genetic modification of the exosomes to overexpress miR-214.

Inhibition of long noncoding RNA growth arrest-specific 5 attenuates cerebral injury induced by deep hypothermic circulatory arrest in rats.

OBJECTIVE: We sought to investigate cerebroprotection by targeting long noncoding RNA growth arrest-specific 5 in a rat model of prolonged deep hypothermic circulatory arrest. METHODS: Deep hypothermic circulatory arrest was conducted for 60 minutes when the pericranial temperature was cooled to 18°C in rats. Dual luciferase assay was used to detect the binding relationship between growth arrest-specific 5 and putative target microRNAs. Adeno-associated viral vectors containing growth arrest-specific 5 small interfering RNA or negative control small interfering RNA were administered by intracerebroventricular injection 14 days before deep hypothermic circulatory arrest. Expressions of growth arrest-specific 5, microRNA-23a, phosphate and tension homology, Bcl-2-associated X protein, Bcl-2, phospho-protein kinase B, protein kinase B, and cleaved caspase-3 in the hippocampus were measured by quantitative reverse transcription polymerase chain reaction and Western blot. Spatial learning and memory functions were evaluated by the Morris water maze test. The hippocampus was harvested for histologic examinations and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining. RESULTS: Luciferase assay showed that growth arrest-specific 5 targeted and inhibited microRNA-23a expression. After deep hypothermic circulatory arrest, hippocampal growth arrest-specific 5 expression was significantly enhanced with a robust decrease of hippocampal microRNA-23a expression. Small interfering RNA growth arrest-specific 5 significantly inhibited growth arrest-specific 5 expression and enhanced microRNA-23a expression in the hippocampus, accompanied with decreases of phosphate and tension homology and Bcl-2-associated X protein expression, and increases of Bcl-2 expression and phospho-protein kinase B/protein kinase B ratio. Growth arrest-specific 5 knockdown inhibited neuronal apoptosis, attenuated histologic damages, and increased the number of surviving neurons in the hippocampus. Spatial learning and memory functions after deep hypothermic circulatory arrest were also markedly improved by growth arrest-specific 5 inhibition. CONCLUSIONS: Inhibition of large noncoding RNA growth arrest-specific 5 can provide a powerful cerebroprotection against deep hypothermic circulatory arrest, which may be mediated through microRNA-23a/phosphate and tension homology pathway.

Polymer Binders Constructed through Dynamic Noncovalent Bonds for High-Capacity Silicon-Based Anodes.

Silicon (Si) is a promising candidate for high-capacity anode materials owing to its high theoretical capacity (3579 mAh g-1 ), low working voltage, and wide natural abundance, although its huge volume variation during charge/discharge processes always results in a short cycling life. Polymer binders play a vital role in improving the cycling performance of Si-based anodes, although traditional polyvinylidene difluoride cannot fulfil the requirements owing to its weak van der Waals forces with the Si surface. Recently, polymer binders constructed by dynamic bonds have been developed, which are reported to allow high-energy-density electrodes with improved electrochemical performance. With dynamic bonds including hydrogen bonding, ionic bonding, and host-guest interactions, these polymer binders possess self-healing capabilities and enhanced mechanical performance, achieving a tremendous advance in addressing the capacity fading of Si-based anodes. In this review, we will summarize the research progress of polymer binders constructed with dynamic bonds, and the challenges for their real applications in advanced Li-ion batteries will also be discussed.

Inhibition of MicroRNA-204 Conducts Neuroprotection Against Spinal Cord Ischemia.

BACKGROUND: MicroRNA(miR)-204 is an autophagy- and apoptosis-related gene. Neuroprotection by the inhibition of miR-204 against spinal cord ischemia was evaluated, and the roles of neuronal autophagy and apoptosis were investigated. METHODS: Spinal cord ischemia was conducted in rats by cross-clamping the descending aorta for 14 minutes. Inhibition of miR-204 was induced by intrathecal injection of lentivirus vectors containing antagomiR-204. Hind-limb motor function was assessed with the motor deficit index. Lumbar spinal cords were harvested for histologic examinations and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling staining. Autophagy was evaluated by the LC3-II/LC3-I ratio and beclin-1 expression. Expressions of LC3-I, LC3-II, beclin-1, B-cell lymphoma-2 (BCL-2), caspase-3, and miR-204 were measured by Western blot and quantitative real-time polymerase chain reaction. Autophagy was blocked by 3-methyladenine. RESULTS: Transient ischemia enhanced miR-204 expression and the LC3-II/LC3-I ratio and downregulated BCL-2 expression in spinal cords in a time-dependent manner. AntagomiR-204 significantly reduced expressions of miR-204 and caspase-3, dramatically upregulated expressions of beclin-1 and BCL-2 and the LC3-II/LC3-I ratio in spinal cords after reperfusion. Compared with controls, inhibition of miR-204 markedly decreased the motor deficit index scores at 6, 12, 24, and 48 hours after reperfusion; increased the number of viable motor neurons; and decreased the number of apoptotic neurons. 3-Methyladenine completely abolished enhancements of the LC3-II/LC3-I ratio and beclin-1 expression induced by antagomiR-204 and inhibited the protective effect on hind-limb motor function. CONCLUSIONS: Inhibition of miR-204 exerts spinal cord protection against ischemia-reperfusion injury, possibly via promotion of autophagy and antiapoptotic effects.

Exosomes derived from bone marrow mesenchymal stem cells overexpressing microRNA-25 protect spinal cords against transient ischemia.

OBJECTIVE: We investigated the neuroprotection of exosomes derived from bone marrow mesenchymal stem cells overexpressing microRNA-25 on ischemic spinal cords. METHODS: Cultured mesenchymal stem cells were transfected with lentivirus vectors containing pre-microRNA-25 or control vectors. Exosomes were isolated and harvested by centrifugation. Spinal cord ischemia was induced in rats by crossclamping the descending aorta just distal to the left subclavian artery for 15 minutes. Exosomes from mesenchymal stem cells, mesenchymal stem cells transfected with control vector, or pre-microRNA-25 were administered by intrathecal injection before ischemia. Hind-limb motor function was assessed with the motor deficit index. Contents of interleukin-1ß, tumor necrosis factor-α, malondialdehyde, and superoxide dismutase activity were measured using commercial kits. Expressions of NADPH oxidase 2, NADPH oxidase 4, and microRNA-25 were detected by Western blot and quantitative reverse transcription polymerase chain reaction. Lumbar spinal cords were harvested for histologic examination. RESULTS: Transfection of pre-microRNA-25 significantly enhanced microRNA-25 levels in mesenchymal stem cells and their exosomes (P < .001). All exosome-pretreating groups exhibited lower levels of interleukin-1ß and tumor necrosis factor-α (P < .001), more intact motor neurons (P < .001), and lower motor deficit index scores (P < .005) than those of controls. Compared with exosomes, microRNA-25-enriched exosomes markedly enhanced microRNA-25 level (P < .001), inhibited NADPH oxidase 4 expression (P = .012), but not NADPH oxidase 2 expression, decreased malondialdehyde content (P = .022), increased superoxide dismutase activity (P < .001) in spinal cords, and had additional neuroprotective effects as evidenced by lower motor deficit index scores (P < .005) and more survival neurons (P = .002). CONCLUSIONS: The neuroprotection of exosomes from mesenchymal stem cells on ischemic spinal cords can be enhanced by genetic modification of the exosomes to contain elevated microRNA-25.

Chipmunk Brain Is Resistant to Injury from Deep Hypothermic Circulatory Arrest During Cardiopulmonary Bypass.

Chipmunk as a food-storing hibernator naturally undergoes hibernation that is linked to great changes in systemic physiology and could protect the central nervous system during drastically reduced cerebral blood flow and low temperature in hibernation. Deep hypothermic circulatory arrest (DHCA) is associated with neurological dysfunction. We aim to test whether the euthermic chipmunk is resistant to injury from DHCA. Sprague-Dawley (SD) rats were used in a positive control. Ten euthermic chipmunks and 10 rats were subjected to 60-minute DHCA. Sham rats and chipmunks received cannulations. The blood samples after surgery were extracted to measure the tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) level. The levels of opioid receptor delta 1 (OPRD1), mature brain-derived neurotrophic factor (m-BDNF), precursor of BDNF (pro-BDNF), TrkB, GRB2, Erk, p-Erk, P38, Bcl-2, P75NTR, TRAF6, JNK, P53, Bax, and Caspase3 of the hippocampus were analyzed at 24 hours after surgery. The brain of chipmunks and rats were fixed for histopathological assessment. In the DHCA rat group, the levels of TNF-α and IL-6 were greater (p < 0.05) compared with DHCA chipmunks. In the DHCA chipmunk group, the levels of OPRD1, mature BDNF/pro-BDNF, TrkB-FL/TrkB-T1, Bcl-2, and p-Erk/Erk of hippocampus were higher than DHCA rats. The levels of GRB2, P75NTR, TRAF6, P53, Bax, and Caspase3 in DHCA chipmunks were lower than DHCA rats. The histopathological assessment showed that the injury in DHCA rat group was more severe than the DHCA chipmunk group. Euthermic chipmunks were greatly tolerant to global cerebral injury during DHCA. Different isoforms of BDNF might be involved in the resistant strategy.

Overexpression of microRNA-30a contributes to the development of aortic dissection by targeting lysyl oxidase.

OBJECTIVE: To explore the role of microRNA (miR)-30a in the development of aortic dissection. METHODS: Human aortic specimens of aortic dissections and aneurysms were harvested. Aortic specimens from donors for heart transplantation served as controls. Rat aortic vascular smooth muscle cells (VSMCs) were transfected with agomiR-30a or antagomiR-30a, and control cells were incubated with empty vectors. Rats were pretreated with agomiR-30a or antagomiR-30a (5 × 107 transfection units every 3 days for 4 weeks), and empty vectors were infused to controls. Acute aortic dissection was induced by subcutaneous infusion of angiotensin II (1 µg · kg-1 · min-1 for 24 hours). Protein expressions of lysyl oxidase (LOX) and elastin and gene expression of miR-30a were measured in VSMCs and human and rat aortic specimens by Western blot analysis and quantitative real-time polymerase chain reaction. RESULTS: Gene expression of miR-30a was much higher, and protein abundance of LOX and elastin was significantly lower, in the aortic dissection specimens (P < .05 vs controls). Transfection of agomiR-30a markedly decreased the luciferase activity of LOX in VSMCs of wild type, but not of LOX 3'-UTR mutant (P = .002). In cultured VSMCs, transfection of agomiR-30a dramatically enhanced the gene expression of miR-30a and down-regulated the protein abundance of LOX and elastin (P < .05 vs controls). Pretreatment with agomiR-30a in vivo enhanced miR-30a expression and down-regulated the protein abundance of LOX and elastin in rat aortas (P < .05 vs controls). The rate of dissection was significantly higher in rats pretreated with agomiR-30a (P = .003 vs controls). CONCLUSIONS: Overexpression of miR-30a contributes to the development of aortic dissection, possibly by targeting LOX.