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Chemodynamic therapy (CDT) employs Fenton catalysts to kill cancer cells by converting intracellular H 2 O 2 into hydroxyl radical (•OH), but endogenous H 2 O 2 is insufficient to achieve satisfactory anticancer efficacy. Despite tremendous efforts, engineering CDT agents with specific and efficient H 2 O 2 self-supplying ability remains a great challenge. Here, we report the fabrication of copper peroxide (CP) nanodot, which is the first example of a Fenton-type metal peroxide nanomaterial, and its use as an activatable agent for enhanced CDT by self-supplying H 2 O 2 . The CP nanodots were prepared through coordination of H 2 O 2 to Cu 2+ with the aid of hydroxide ion, which could be reversed by acid treatment. After endocytosis into tumor cells, acidic environment of endo/lysosomes accelerated the dissociation of CP nanodots, allowing simultaneous release of Fenton catalytic Cu 2+ and H 2 O 2 accompanied by a Fenton-type reaction between them. The resulting •OH induced lysosomal membrane permeabilization through lipid peroxidation and thus caused cell death via a lysosome-associated pathway. In addition to pH-dependent •OH generation property, CP nanodots with small particle size showed high tumor accumulation after intravenous administration, which enabled effective tumor growth inhibition with minimal side effects in vivo. Our work not only provides the first paradigm for fabricating Fenton-type metal peroxide nanomaterials, but also presents a new strategy to improve CDT efficacy.

Weyl semimetals provide the realization of Weyl fermions in solid-state physics. Among all the physical phenomena that are enabled by Weyl semimetals, the chiral anomaly is the most unusual one. Here, we report signatures of the chiral anomaly in the magneto-transport measurements on the first Weyl semimetal TaAs. We show negative magnetoresistance under parallel electric and magnetic fields, that is, unlike most metals whose resistivity increases under an external magnetic field, we observe that our high mobility TaAs samples become more conductive as a magnetic field is applied along the direction of the current for certain ranges of the field strength. We present systematically detailed data and careful analyses, which allow us to exclude other possible origins of the observed negative magnetoresistance. Our transport data, corroborated by photoemission measurements, first-principles calculations and theoretical analyses, collectively demonstrate signatures of the Weyl fermion chiral anomaly in the magneto-transport of TaAs.

The movement of anionic porphyrins (for example, haem) across intracellular membranes is crucial to many biological processes, but their mitochondrial translocation and coordination with haem biosynthesis is not understood. Transport of porphyrins into isolated mitochondria is energy-dependent, as expected for the movement of anions into a negatively charged environment. ATP-binding cassette transporters actively facilitate the transmembrane movement of substances. We found that the mitochondrial ATP-binding cassette transporter ABCB6 is upregulated (messenger RNA and protein in human and mouse cells) by elevation of cellular porphyrins and postulated that ABCB6 has a function in porphyrin transport. We also predicted that ABCB6 is functionally linked to haem biosynthesis, because its mRNA is found in both human bone marrow and CD71+ early erythroid cells (by database searching), and because our results show that ABCB6 is highly expressed in human fetal liver, and Abcb6 in mouse embryonic liver. Here we demonstrate that ABCB6 is uniquely located in the outer mitochondrial membrane and is required for mitochondrial porphyrin uptake. After ABCB6 is upregulated in response to increased intracellular porphyrin, mitochondrial porphyrin uptake activates de novo porphyrin biosynthesis. This process is blocked when the Abcb6 gene is silenced. Our results challenge previous assumptions about the intracellular movement of porphyrins and the factors controlling haem biosynthesis.

Quantum spin liquid (QSL) is a novel state of matter which refuses the conventional spin freezing even at 0 K. Experimentally searching for the structurally perfect candidates is a big challenge in condensed matter physics. Here we report the successful synthesis of a new spin-1/2 triangular antiferromagnet YbMgGaO4 with symmetry. The compound with an ideal two-dimensional and spatial isotropic magnetic triangular-lattice has no site-mixing magnetic defects and no antisymmetric Dzyaloshinsky-Moriya (DM) interactions. No spin freezing down to 60 mK (despite θw ~ −4 K), the power-law temperature dependence of heat capacity and nonzero susceptibility at low temperatures suggest that YbMgGaO4 is a promising gapless (≤|θw|/100) QSL candidate. The residual spin entropy, which is accurately determined with a non-magnetic reference LuMgGaO4, approaches zero (<0.6%). This indicates that the possible QSL ground state (GS) of the frustrated spin system has been experimentally achieved at the lowest measurement temperatures.

Accruing data suggest that oxidative stress may be a factor underlying the pathophysiology of bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SCZ). Glutathione (GSH) is the major free radical scavenger in the brain. Diminished GSH levels elevate cellular vulnerability towards oxidative stress; characterized by accumulating reactive oxygen species. The aim of this study was to determine if mood disorders and SCZ are associated with abnormal GSH and its functionally related enzymes. Post-mortem prefrontal cortex from patients with BD, MDD, SCZ, and from non-psychiatric comparison controls were provided by the Stanley Foundation Neuropathology Consortium. Spectrophotometric analysis was utilized for the quantitative determination of GSH, while immunoblotting analyses were used to examine expression of glutamyl-cysteine ligase (GCL), GSH reductase (GR), and GSH peroxidase (GPx). We found that the levels of reduced, oxidized, and total GSH were significantly decreased in all psychiatric conditions compared to the control group. Although GCL and GR levels did not differ between groups, the levels of GPx were reduced in MDD and SCZ compared to control subjects. Since oxidative damage has been demonstrated in MDD, BD, and SCZ, our finding that GSH levels are reduced in post-mortem prefrontal cortex suggests that these patient groups may be more susceptible to oxidative stress.

Magnetic resonance is essential in revealing the structure and dynamics of biomolecules. However, measuring the magnetic resonance spectrum of single biomolecules has remained an elusive goal. We demonstrate the detection of the electron spin resonance signal from a single spin-labeled protein under ambient conditions. As a sensor, we use a single nitrogen vacancy center in bulk diamond in close proximity to the protein. We measure the orientation of the spin label at the protein and detect the impact of protein motion on the spin label dynamics. In addition, we coherently drive the spin at the protein, which is a prerequisite for studies involving polarization of nuclear spins of the protein or detailed structure analysis of the protein itself.

We report here results from a Chandra ACIS observation of the stellar populations in and around the Messier 17 HII region. The field reveals 886 sources with observed X-ray luminosities (uncorrected for absorption) between ∼ 29.3 < log L x < 32.8 ergs s −1 , 771 of which have stellar counterparts in infrared images. In addition to comprehensive tables of X-ray source properties, several results are presented:1. The X-ray Luminosity Function is calibrated to that of the Orion Nebula Cluster population to infer a total population of roughly 8000-10,000 stars in M17, one-third lying in the central NGC 6618 cluster.2. About 40% of the ACIS sources are heavily obscured with A V > 10 mag. Some are concentrated around well-studied star-forming regions-IRS 5/UC1, the Kleinmann-Wright Object, and M17-North-but most are distributed across the field. As previously shown, star formation appears to be widely distributed in the molecular clouds. X-ray emission is detected from 64 of the hundreds of Class I protostar candidates that can be identified by near-and mid-infrared colors. These constitute the most likely protostar candidates known in M17.3. The spatial distribution of X-ray stars is complex: in addition to the central NGC 6618 cluster and well-known embedded groups, we find a new embedded cluster (designated M17-X), a 2 pc-long arc of young stars along the southwest edge of the M17 HII region, and 0.1 pc substructure within various populations. These structures may indicate that the populations are dynamically young.4. All (14/14) of the known O stars but only about half (19/34) of the known B0-B3 stars in the M17 field are detected. These stars exhibit the long-reported correlation between X-ray and bolometric luminosities of L x ∼ 10 −7 L bol . While many O and early B stars show the soft X-ray emission expected from microshocks in their winds or moderately hard emission that could be caused by magnetically channeled wind shocks, six of these stars exhibit very hard thermal plasma components (kT > 4 keV) that may be due to colliding wind binaries. More than 100 candidate new OB stars are found, including 28 X-ray detected intermediateand high-mass protostar candidates with infrared excesses.5. Only a small fraction (perhaps 10%) of X-ray selected high-and intermediate-mass stars exhibit K-band emitting protoplanetary disks, providing further evidence that inner disks evolve very rapidly around more massive stars.Subject headings: open clusters and associations: individual (M17) -X-rays: individual (M17) -stars: early-type -stars: pre-main-sequence -X-Rays: starsIn the high-energy regime, lower-mass young stars in nearby star-forming regions were studied extensively with X-ray missions during the 1980-90s (Feigelson & Montmerle 1999), but studies of the more distant MSFRs were hampered by the limited spatial resolution of these telescopes. The launch of the Chandra X-ray Observatory (Weisskopf et al. 2002) in 1999 makes X-ray studies of MSFRs much more feasible, due to the sub-arcsecond spatial resolution of its mir...