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Huntington's disease (HD) usually causes cognitive disorders, including learning difficulties, that emerge before motor symptoms. Mutations related to lysosomal trafficking are linked to the pathogenesis of neurological diseases, whereas the cellular mechanisms remain elusive. Here, we discover a reduction in the dendritic density of lysosomes in the hippocampus that correlates with deficits in synaptic plasticity and spatial learning in early CAG-140 HD model mice. We directly manipulate intraneuronal lysosomal positioning with light-induced CRY2:CIB1 dimerization and demonstrate that lysosomal abundance in dendrites positively modulates long-term potentiation of glutamatergic synapses onto the neuron. This modulation depends on lysosomal Ca2+ release, which further promotes endoplasmic reticulum (ER) entry into spines. Importantly, optogenetically restoring lysosomal density in dendrites rescues the synaptic plasticity deficit in hippocampal slices of CAG-140 mice. Our data reveal dendritic lysosomal density as a modulator of synaptic plasticity and suggest a role of lysosomal mispositioning in cognitive decline in HD. [Display omitted] • Lysosomes translocate from neuronal dendrites to somata in early HD mice • Dendritic lysosomal abundance positively modulates LTP by regulating Ca2+ • Light-induced CRY2:CIB1 dimerization can manipulate lysosome positioning in neurons • Optogenetic restoration of dendritic lysosomes rescues LTP deficit in early HD mice Chen et al. discover a reduction in lysosome density in dendrites of hippocampal pyramidal neurons in early HD mice that leads to deficits in synaptic plasticity and learning. The plasticity deficit is rescued by optogenetic restoration of dendritic lysosomes through light-induced CRY2:CIB1 dimerization. [ABSTRACT FROM AUTHOR]

Abstract A bio-based poly (urethane urea) (CIPUU) network comprised of castor oil (CO), isosorbide (IS) and 4-aminophenyl disulfide (APD) was prepared and compared to the corresponding polyurethane (CIPU) consisting of CO and IS. Permanently cross-linked CIPU could not be reprocessed, while CIPUU could be reprocessed, as the network topology could rearrange through an associative disulfide exchange reaction. CIPUU had a higher Young's modulus than CIPU due to the higher rigidity of APD with benzene rings and the formed hydrogen bonding of the urea unit. Stress relaxation measurement indicated that the network topology of CIPUU was stable at temperatures lower than 100 °C due to the inactive disulfide exchange reaction at low temperatures. The exchange reaction became increasingly active with increasing temperature, as evidenced by the gradually reduced relaxation time. CIPUU showed excellent reprocessability, as indicated by the remaining gel fraction and fully recovered mechanical properties after thermal remoulding at 180 °C several times. In addition, CIPUU showed good thermal stability with an onset decomposition temperature (∼260 °C) much higher than the reprocessing temperature. Highlights • Poly (urethane urea) network consists of castor oil, isosorbide and 4-aminophenyl disulfide. • The poly (urethane urea) showed high modulus than the polyurethane without 4-aminophenyl disulfide. • Stress relaxation of the poly (urethane urea) became prominent at elevated temperatures. • The poly (urethane urea) network could be reprocessed without losing mechanical properties. • The poly (urethane urea) network showed good thermal stability. [ABSTRACT FROM AUTHOR]

Graphical abstract Schematic diagram showing the mechanism underlying endogenous n-3, PUFA-mediated inhibition of AOM-induced colon tumorigenesis in mice fed a, high-fat diet (HFD). Endogenously synthesised n-3 PUFAs promoted colon tumour cell apoptosis and suppressed proliferation in colon tissue by inhibiting inflammation pathways, including the IL-6/STAT3 and TNF-α/NF-κB pathways and downregulating the activity of the NLRP3 inflammasome, thus, inhibiting colon tumorigenesis in fat-1 mice. Highlights • A high-fat diet (HFD) enhanced AOM-induced colon tumorigenesis in WT mice. • HFD promotes AOM-induced colon tumour development via multiple inflammatory signalling pathways. • Endogenous n-3 PUFAs inhibit colon tumorigenesis. Abstract Literature suggests important roles of a high-fat diet (HFD) in tumour development, but the underlying mechanisms remain poorly understood. This study assessed the protective effect of n-3 polyunsaturated fatty acids (PUFAs) on HFD-enhanced colon tumours and the underlying mechanism. WT mice were fed a normal fat diet or HFD and Fat-1 mice were fed a HFD for 22 weeks. For weeks 1–6, all mice were intraperitoneally administered AOM weekly. HFD significantly enhanced AOM-induced colon tumorigenesis in WT mice; however, tumour incidence and multiplicity were markedly lower in Fat-1 mice. HFD-triggered tumour development involved the activation of inflammatory signalling pathways, including TNF-α/NF-κB, IL-6/STAT3, and downstream NLRP3/IL-1β pathways and upregulation of β-catenin/c-myc pathway, which is associated with cancer cell proliferation. n-3 PUFAs inhibited colon tumour development and mitigated the changes to the aforementioned inflammatory pathways and oncogenic signalling. We provide experimental evidence for the role of n-3 PUFAs as potential chemopreventive agents against colon cancer. [ABSTRACT FROM AUTHOR]

Fire hazard and waste crisis are two challenges for thermosets, particularly for epoxy resins (EPs) possessing the largest market share therein; yet it is beset with difficulties to solve the challenges simultaneously. Herein, a commercialized phosphorus-containing diol named diethyl bis(2-hydroxyethyl)aminomethylphosphonate (DAP) with "trinity" structures containing phosphonate ester, primary hydroxyls and tertiary amine was applied in an epoxy-anhydride curing system to achieve the catalyst-free mixed transesterification within the adaptable carboxylate/phosphonate networks. The phosphonate structure in DAP was covalently bonded into the epoxy vitrimers (EVs), endowing the EVs with intrinsic fire safety. In detail, the peak heat release rate (PHRR), total heat release (THR), total smoke production (TSP) and maximum smoke density (Ds max) values were considerably reduced by 62.0%, 73.6%, 78.9% and 70.8%, respectively. Meanwhile, owing to the self-catalytic tertiary amine and highly reactive primary hydroxyls from DAP, the mixed transesterification within the adaptable carboxylate/phosphonate networks was accelerated, endowing facile reprocessibility and malleability of the vitrimers, which were further degraded into low-mass molecules by simple alcoholysis. Killing two birds with one stone, this work provided a promising and feasible way to make sustainable and fire-safe thermosetting polymers with comprehensive properties. [Display omitted] • Catalyst-free adaptable carboxylate/phosphonate networks were used to construct intrinsically fire-safe epoxy vitrimers. • The vitrimers exhibited observable suppression on heat, smoke and toxic gas during burning. • The vitrimers showed desirable malleability without sacrificing intrinsic fire safety. • Degradation of the vitrimers was achieved via simple alcoholysis, showing multi-path recyclability. [ABSTRACT FROM AUTHOR]

Energy conversion devices such as alkaline fuel cells (AFCs) rely critically on anion exchange membranes (AEMs) with high hydroxide conductivity as well as good chemical stability. Poly (crown ether) (PCE) based AEMs with different aliphatic chain lengths in polymer backbone are successfully designed and prepared in this study. The longer hydrophobic aliphatic chain segments can promote the formation of nanophase separation and ionic clusters. As examined by morphology observation such as atomic force microscopy (AFM), small angle X-ray scattering (SAXS) and transmission electron microscopy (TEM), the QAPCE-16C AEMs which the carbon number of aliphatic chains is sixteen show a well-connected ion cluster region and a distinct micromorphology separation. QAPCE-16C with an IEC of 1.43 meq g−1 shows a hydroxide conductivity of 125 mS cm−1 at 80 °C. After immersing in a 1 M sodium hydroxide solution at 80 °C for 960 h, QAPCE-16C presents good alkaline resistance with the ionic conductivity retention of 95.77%. Besides this, the peak power density of QAPCE-16C can reach to 653.8 mW cm−2 in H 2 /O 2 as well as 458.8 mW cm−2 in H 2 /Air (CO 2 -free) at 80 °C. [Display omitted] • Effect of aliphatic chain lengths on the performance of AEMs is investigated. • Introduction of aliphatic chain promotes the microphase structure of AEMs. • The QAPCE-16C AEMs show the maximum OH− conductivity of 125 mS cm−1 at 80 °C. • Power density of 653.8 mW cm−2 in a H 2 /O 2 single cell based on QAPCE-16C is obtained. [ABSTRACT FROM AUTHOR]

Castor oil (CO) derived polyurethane networks exhibit poor mechanical properties and non-reprocessibility due to flexible, highly and permanently cross-linked network structures. To overcome these defects, we designed and fabricated a series of poly (urethane urea) (PUU) networks by reacting CO-based polyurethane precursor with different amounts of 4-aminophenyl disulfide (APD). The equilibrium swelling behavior, mechanical properties, stress relaxation and reprocessibility of the COPUU networks were investigated in detail in this study. The swelling ratio increased with increasing APD content due to the reduced crosslink density. The mechanical properties of the COPUU networks are tunable over a broad range (either as elastomers or as plastics) depending on the APD component inputs. The tensile strength, Young's modulus and elongation at break for COPUU composed of CO/APD (W/W, 7:3) were improved by 11.7, 2.7 and 5.2 times, respectively, compared to the control CO-based polyurethane without APD. The COPUU can be reprocessed though thermal compression molding and the mechanical properties recovered completely after reprocessing at 180 °C for several cycles. The stress relaxation of COPUU accelerated with increasing APD content due to the increasing concentration of exchangeable disulfide linkage. [ABSTRACT FROM AUTHOR]

We have investigated the structural, magnetic and electrical transport properties of the Ni doped FeRh films prepared by magnetron co-sputtering. A large magetoresistance of 35%, induced by a reversible antiferromagnetic to ferromagnetic phase transition, is obtained at room temperature with only 1 mol.% Ni addition. Magnetic field is revealed to have an equivalent effect as temperature to drive the magnetic phase transition. Moreover, the way to realize a nonvolatile room temperature magetoresistance effect is also discussed. These results give FeRh the possibility of technological application in the spintronic field at room temperature, which are referential to other material systems with a first-order magnetic phase transition. [ABSTRACT FROM AUTHOR]

Flame retardancy and recyclability are two important issues in the research field of thermosets, particularly for epoxy resin (EP) with the biggest market share. It is of great importance, but rarely achievable, to integrate these properties simultaneously into EP. Herein, we report a facile way to prepare intrinsically flame-retardant epoxy vitrimers combining rapid recycling and multiple shape memory effects by introducing dynamic ester-linkages with catalytic transesterification activity into the crosslinking networks of EP. The flame-retardant epoxy vitrimers exhibited high T g (∼110.7 °C), desirable thermal stability and excellent flame retardancy with UL-94 V-0 rating, and high LOI of ∼34%. Also, the value of the peak heat release rate (PHRR) and the total heat release (THR) showed 63% and 32% reduction, respectively. Meanwhile, flame-retardant epoxy vitrimers showed high malleability that could be reprocessed in 15 min at 200 °C without sacrificing the mechanical properties and flame retardancy. Moreover, the dynamic transesterification network allowed flame-retardant EP to access multiple shape memory effect. The design of flame-retardant epoxy vitrimers provide a prime example to foster the cyclic utilization of flame-retardant thermosetting polymers. [Display omitted] • A facile strategy was proposed to prepare intrinsically flame-retardant epoxy vitrimers. • The epoxy vitrimers owned high T g , desirable thermal stability and excellent flame retardancy. • The epoxy vitrimers displayed fast recyclability (∼15 min) without loss in flame retardancy and mechanical properties. • The multiple shape memory performance of the epoxy vitrimers was easily manipulated. [ABSTRACT FROM AUTHOR]

The first conjugate addition of α-isocyanoacetates with in situ generated azoalkenes from α-halogeno hydrazones in the presence of Cs 2 CO 3 has been developed. The reaction condition was suitable to various α-aryl substituted isocyanoacetates as well as aryl and alkyl-substituted α-halogeno hydrazones, affording the corresponding products in good to high yields. The adducts can be easily transformed into biologically attractive 1,4-dihydropyrimidine derivatives via an intramolecular cyclization by treating with AgOAc. The one-pot conjugate addition/intramolecular cyclization has also been investigated to furnish the formal [3 + 3] cycloadduct, 1,4-dihydropyrimidine derivatives. [Display omitted] [ABSTRACT FROM AUTHOR]

To develop highly efficient photosensitizers for photodynamic therapy, herein a zinc(II) phthalocyanine-folate conjugate (PcN - FA) used to construct an activatable nanophotosensitizer (NanoPcN - FA) through a facile self-assembly. The self-assembled nanophotosensitizer (NanoPcN) without folate-modification was used as a negative control. After self-assembly, the photoactivities of NanoPcN - FA was quenched. The in vitro studies showed that NanoPcN - FA could be taken in by folate-receptor (FR)-positive SKOV3 cells and activated in the cells. It also exhibited slightly higher photocytotoxicity against SKOV3 cells than NanoPcN. Moreover, the competitive assay confirmed that the cellular uptake of NanoPcN - FA was through a FR-mediated process. Finally, the in vivo results indicated that NanoPcN - FA could target tumor tissue of S180 rat ascitic tumor-bearing mice due to the folic acid (FA) ligand, leading to a highly efficient antitumor photodynamic efficacy with the tumor inhibition rate of 95%. [Display omitted] • A phthalocyanine-folate conjugate self-assembled into activatable nanophotosensitizer. • The photoactivities of the phthalocyanine were quenched in the nanophotosensitizer. • It was taken in by folate receptor (FR)-positive cells through a FR-mediated pathway. • The quenched photoactivities could be activated in FR-positive cells and tumor tissues. • It had efficient tumor targeting and in vivo photodynamic anticancer efficacy. [ABSTRACT FROM AUTHOR]

Abstract Hydrogen-rich water (HRW) has been widely used in research on plant resistance to Cd. However, the underlying molecular mechanism of HRW in ameliorating cadmium stress in vegetables is largely unknown. In this study, the RNA-sequencing analyses were used to characterize the role of HRW in the alleviation of Cd toxicity in Chinese cabbage seedlings. Based on the obtained results, two genes encoding metal ionic transporters, BcIRT1 and BcZIP2 were ultimately selected out. Then, a systematic validation of the metal ion transport function of these two ZIP-encoding genes of pak choi were performed via a yeast transformation system. The results showed that BcIRT1 and BcZIP2 increased the sensitivity of different yeast mutant strains to relative metal ionic stresses and facilitated the accumulation of metal ions (Cd2+, Mn2+, Zn2+, and Fe2+) in yeast; thus, it suggests that BcIRT1 and BcZIP2 probably have the ability to transport Cd2+, Mn2+, Zn2+ and Fe2+ in pak choi. The time-course and concentration-dependent expression profiles of BcIRT1 and BcZIP2 showed that as time with HRW increased, the effectiveness of the repression on the expression of BcIRT1 and BcZIP2 increased, and as the seedlings were exposed to increased Cd concentrations, the inhibition of BcIRT1 and BcZIP2 by HRW was also increased. Over all, these findings provide new insights into the genome-wide transcriptome profiles in pak choi and show that HRW reduced Cd uptake probably through inhibiting the expression of transporters related to Cd absorption, BcIRT1 and BcZIP2. Highlights • Transcriptome profiles induced by Cd or HRW plus Cd were obtained. • HRW efficiently regulated the expression of Cd-induced transporter related genes. • The first function validation of BcIRT1 and BcZIP2 were performed by a yeast system. [ABSTRACT FROM AUTHOR]

• Oleosins play essential roles in stabilization of lipid droplets (LDs) and seed oil production. • 65 oleosin genes were identified in genome-sequenced Theaceae species. • Most oleosin genes displayed inter-species synteny among tea and oil tea species. • Our findings provide valuable information for further functional analysis and utilization of oleosin genes in tea and oil tea. Oleosins play essential roles in stabilization of lipid droplets (LDs) and seed oil production. However, evolution of this gene family has not been reported in Theaceae, a large plant family that contains many important tea and oil tea species. In this study, a total of 65 oleosin genes were identified in nine genome-sequenced Theaceae species. Among these genomes, the gene number of oleosin showed significant difference, with Camellia sinensis var. sinensis cv. Shuchazao and Camellia lanceoleosa displayed more oleosin numbers than other species. Phylogenetic analyses revealed that Theaceae oleosin genes were classified into three clades (U, SL, SH) respectively. Proteins within the same clade had similar gene structure and motif composition. Segmental duplication was the primary driving force for the evolution of oleosin genes in Shuchazao (SCZ), Huangdan (HD), C.lanceoleosa (Cla), and wild tea (DASZ). Synteny analysis showed that most oleosin genes displayed inter-species synteny among tea and oil tea species. Expression analysis demonstrated that oleosin genes were specifically expressed in seed and kernel of Huangdan (HD) and C.lanceoleosa. Moreover, expression divergence was observed in paralogous pairs and ∼1–2 oleosin genes in each clade have become activate. This study leads to a comprehensive understanding of evolution of oleosin family in Theaceae, and provides a rich resource to further address the functions of oleosin in tea and oil tea species. [ABSTRACT FROM AUTHOR]

Phthalocyanines are promising photosensitizers for photodynamic therapy (PDT), but the inherent tendency of aggregation generally leads to the decrease or even quenching of photoactivities. To address this issue and realize the desirable photodynamic therapeutic effect of phthalocyanines, herein, we report a folate-modified phthalocyanine-based liposomal nanophotosensitizer (PcN@Lip-FA), which can be prepared through a facile "one-pot" method. An analogue (PcN@Lip) without folate was also prepared as a negative control. The liposomal nanophotosnesitizers greatly prevented the aggregation of the zinc(II) phthalocyanine (PcN) and showed highly efficient photoactivities (fluorescence and singlet oxygen generation) in aqueous solutions, although the free PcN is severely aggregated and its photoactivities are nearly quenched. The in vitro results demonstrate that PcN@Lip-FA can be taken in by folate receptor (FR)-positive HeLa cells through FR-mediated process, and exhibits significantly higher cellular uptake and photocytotoxicity against HeLa cells than both PcN@Lip and PcN , but for FR-negative MCF-7 cells, PcN@Lip-FA and PcN@Lip show comparable photocytotoxicity. In addition, with the folate vector, PcN@Lip-FA has highly efficient tumor targeting and PDT effect on the S180 rat ascitic tumor-bearing mice with a tumor inhibition rate up to 98.0%. Therefore, the liposomal nanophotosensitizer PcN@Lip-FA can serve as a promising nanoplatform for cancer diagnosis and targeted PDT. Image 1 • A folate-modified phthalocyanine-based liposomal nanophotosnesitizer was prepared. • The liposomal carrier reduced aggregation and enhanced photoactivities of free PcN. • PcN@Lip-FA could selectively kill HeLa cells with enhanced photodynamic activity. • PcN@Lip-FA had highly efficient tumor targeting and in vivo photodynamic efficacy. • Its tumor inhibition rate on the S180 rat ascitic tumor-bearing mice was up to 98.0%. [ABSTRACT FROM AUTHOR]