CCR5 is the major co-receptor used by HIV-1 and individuals homozygous for a 32bp deletion in CCR5 are profoundly resistant to HIV-1 infection. Using engineered zinc finger nucleases (ZFNs), we were able to disrupt the CCR5 gene in human hematopoietic stem/progenitor cells (HSC) at a mean frequency of 17% of total alleles in a population. This procedure produces both mono and bi-allelically disrupted cells. ZFN-treated HSC retained the ability to engraft NOD/SCID/IL2rγnull mice and gave rise to polyclonal multi-lineage progeny with the CCR5 gene permanently disrupted. Control mice receiving untreated HSC and challenged with CCR5-tropic HIV-1 displayed profound CD4+ T cell loss. In contrast, mice transplanted with ZFN-modified HSC underwent rapid selection for CCR5-negative cells, had significantly lower HIV-1 levels and preserved human cells throughout their tissues. The demonstration that a minority of CCR5-modified HSC can populate an infected animal with HIV-1-resistant, CCR5-negative progeny suggests the use of ZFN-modified autologous HSC as a clinical approach to treating HIV-1.

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Empathy refers to the ability to perceive and share another person's affective state. Much neuroimaging evidence suggests that observing others' suffering and pain elicits activations of the anterior insular and the anterior cingulate cortices associated with subjective empathetic responses in the observer. However, these observations do not provide causal evidence for the respective roles of anterior insular and anterior cingulate cortices in empathetic pain. Therefore, whether these regions are 'necessary' for empathetic pain remains unknown. Herein, we examined the perception of others' pain in patients with anterior insular cortex or anterior cingulate cortex lesions whose locations matched with the anterior insular cortex or anterior cingulate cortex clusters identified by a meta-analysis on neuroimaging studies of empathetic pain perception. Patients with focal anterior insular cortex lesions displayed decreased discrimination accuracy and prolonged reaction time when processing others' pain explicitly and lacked a typical interference effect of empathetic pain on the performance of a pain-irrelevant task. In contrast, these deficits were not observed in patients with anterior cingulate cortex lesions. These findings reveal that only discrete anterior insular cortex lesions, but not anterior cingulate cortex lesions, result in deficits in explicit and implicit pain perception, supporting a critical role of anterior insular cortex in empathetic pain processing. Our findings have implications for a wide range of neuropsychiatric illnesses characterized by prominent deficits in higher-level social functioning.

Obesity is a significant risk factor for cancer. A link between obesity and a childhood cancer has been identified: obese children diagnosed with high-risk acute lymphoblastic leukemia (ALL) had a 50% greater risk of relapse than their lean counterparts. L-asparaginase (ASNase) is a first-line therapy for ALL that breaks down asparagine and glutamine, exploiting the fact that ALL cells are more dependent on these amino acids than other cells. In the present study, we investigated whether adipocytes, which produce significant quantities of glutamine, may counteract the effects of ASNase. In children being treated for high-risk ALL, obesity was not associated with altered plasma levels of asparagine or glutamine. However, glutamine synthetase was markedly increased in bone marrow adipocytes after induction chemotherapy. Obesity substantially impaired ASNase efficacy in mice transplanted with syngeneic ALL cells, and, like in humans, without affecting plasma asparagine or glutamine levels. In co-culture, adipocytes inhibited leukemic cell cytotoxicity induced by ASNase, and this protection was dependent on glutamine secretion. These findings suggest that adipocytes work in conjunction with other cells of the leukemia microenvironment to protect leukemia cells during ASNase treatment.

Background and aimsAdolescent smartphone addiction has received increased attention in recent years, and peer relationship has been found to be a protective factor in adolescent smartphone. However, little is known about the mediating and moderating mechanisms underlying this relation. The aim of this study was to investigate (a) the mediating role of self-esteem in the association between student–student relationship and smartphone addiction, and (b) the moderating role of the need to belong in the indirect relationship between student–student relationship and adolescent smartphone addiction.MethodsThis model was examined with 768 Chinese adolescents (mean age = 16.81 years, SD = 0.73); the participants completed measurements regarding student–student relationship, self-esteem, the need to belong, and smartphone addiction.ResultsThe correlation analyses indicated that student–student relationship was significantly negatively associated with adolescent smartphone addiction, and the need to belong was significantly positively associated with adolescent smartphone addiction. Mediation analyses revealed that self-esteem partially mediated the link between student-student relationship and adolescent smartphone addiction. Moderated mediation further indicated that the mediated path was weaker for adolescents with lower levels of the need to belong.Discussion and conclusionHigh self-esteem could be a protective factor against smartphone addiction for adolescents with a strong need to belong as these students appeared to be at elevated risk of developing smartphone addiction.

Coupling quinone cathode with ionic liquid electrolyte is demonstrated to build high-energy and long-life sodium-ion batteries. Computational and spectroscopic studies reveal that the inhibitory effect of ionic liquid on dissolution of quinone correlates with the strong polarity, weak electron donor ability, and low interaction energy. The calix[4]quinone and 5,7,12,14-pentacenetetrone cathodes exhibit significantly improved cycling performance in N-methyl-N-propylpyrrolidinium bis(trifluoromethanesulfonyl)amide than in ether electrolyte. These results would enlighten the design and application of ionic liquid and quinones for organic batteries. HIGHLIGHTSA facile strategy is proposed to suppress the dissolution of quinone electrodes Inhibitory effect of ILs correlates to polarity, donor number, and binding energy [PY13][TFSI] markedly inhibits quinone dissolution C4Q and PT cathodes exhibit better capacity retention in ILs than in ether Wang et al., Chem 5, 364-375 February 14, SUMMARYQuinone-based sodium-ion batteries (SIBs) are highly desirable electrochemical devices with high capacity and low cost but suffer from poor cycle life and low practical energy because of quinone dissolution in aprotic electrolyte. Herein, we report a facile strategy of using ionic liquid (IL) to tackle the dissolution of quinone electrodes. The inhibitory effect of ILs on quinone dissolution correlates with their polarity, donor number, and interaction energy, as revealed by combined density functional theory and spectroscopy studies. Particularly, in N-methyl-N-propylpyrrolidinium bis(trifluoromethanesulfonyl)amide ([PY13] [TFSI]) electrolyte with weak donor ability and large polarity, calix[4]quinone cathode exhibits high capacity (>400 mAh g À1 ) and superior capacity retention ($99.7% at 130 mA g À1 for 300 cycles), significantly outperforming that in etherbased electrolyte. Moreover, the remarkable cyclability and considerable rate capability of 5,7,12,14-pentacenetetrone in [PY13][TFSI] render it a promising sodium-storage material. This work would promote the development of highperformance SIBs with quinone electrodes and IL electrolyte.

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A SiO nanoparticle decorated polypropylene (PP) separator (PP-SiO) has been prepared by simply immersing the PP separator in the hydrolysis solution of tetraethyl orthosilicate (TEOS) with the assistance of Tween-80. After decoration, the thermal stability and the electrolyte wettability of the PP-SiO separator are obviously improved. When the PP-SiO separator is used for lithium-sulfur (Li-S) batteries, the cyclic stability and rate capability of the batteries are greatly enhanced. The capacity retention ratio of the Li-S battery configured with the PP-SiO separator is 64% after 200 cycles at 0.2 C, which is much higher than that configured with the PP separator (45%). Moreover, the rate capacity of the Li-S batteries using the PP-SiO separator reaches 956.3, 691.5, 621, and 567.6 mAh g at the current density of 0.2, 0.5, 1, and 2 C, respectively. The reason could be ascribed to that the polar silica coating not only alleviates the shuttle effect but also facilitates Li-ion migration.