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Porous carbon nanosheets with high specific surface area have become the most promising electrode materials for supercapacitor, but their high pore volume leads to relatively low density and poor volumetric capacitance. In this work, strutted nitrogen doped hierarchical porous carbon nanosheets (SNPCNS), featuring three-dimensional nonaggregated architecture braced by struts have successfully been scalably synthesized via a novel calcium d -gluconate-exploding technique. The pyrolysis temperature and duration, and the mass ratio of calcium d -gluconate and urea formaldehyde resin are regulated for optimizing the specific surface area, pore volume and capacitive performance of SNPCNS. The optimized SNPCNS displays high specific surface area (539 m2 g−1), rich surface heteroatoms (8.1 at.% for N) and high density (1.11 g cm−3). Therefore, the supercapacitor assembled by SNPCNS electrodes presents very high gravimetric/volumetric capacitances of 286 F g−1/317 F cm−3 (in 6 M KOH) and 355 F g−1/394 F cm−3 (in 1 M H2SO4). Importantly, high gravimetric/volumetric energy densities of 40.5 W h kg−1/44.9 W h L−1 (in ionic liquid) are achieved, which are superior to those of previously reported carbon nanosheets based symmetric supercapacitors. This work provides a new strategy for the mass and low-cost production of high-performance porous carbon nanosheets for energy storage.

There are lacking standard treatment guidelines for aggressive fibromatosis (AF) because of its rarity.This study aimed to investigate the risk factors for recurrence and survival of abdominal AF after radical surgical resection.From August 2012 to December 2020, a retrospective analysis was conducted on the clinical data of 69 AF in Shanghai Public Health Clinical Center Affiliated to Fudan University, with the tumor locating either in the abdominal wall or in the abdominal cavity. The main observation end point was progression-free survival time (PFS) and overall survival time (OS).All 69 patients achieved microscopic R0 resection, 10 (14.5%) had local recurrence, and 3 (4.3%) died. The PFS rate after 1, 3, 5, and 10 years was 96.8%, 87.7%, 78.8%, and 78.8%, respectively. The OS rate after 1, 3, 5, and 10 years was 100%, 100%, 92.9%, and 81.3%, respectively. In 10 patients with recurrence, the median recurrence time was 17.6 months. Concomitant familial adenomatous polyposis (FAP) and history of previous recurrence were independent risk factors of post-operative recurrence.After radical surgery of abdominal AF, the local recurrence rate was 15%. Concomitant FAP and a previous history of recurrence were independent risk factors of post-operative recurrence. R0 and a combined organ resection should be performed especially in FAP patients to minimize the recurrence and improve the prognosis.The present study identifies the risk factors of recurrence in AF and suggests R0 resection especially in concomitant FAP patients. A wait-and-see strategy should not be generally implemented and radical surgery will bring clinical benefits to patients with such kind of rare disease.

Spin-current and spin-wave-based devices have been considered as promising candidates for next-generation information transport and processing and wave-based computing technologies with low-power consumption. Spin pumping has attracted tremendous attention and has led to interesting phenomena, including the line width broadening, which indicates damping enhancement due to energy dissipation. Recently, chiral spin pumping of spin waves has been experimentally realized and theoretically studied in magnetic nanostructures. Here, we experimentally observe by Brillouin light scattering (BLS) microscopy the line width broadening sensitive to magnetization configuration in a hybrid metal-insulator nanostructure consisting of a Co nanowire grating dipolarly coupled to a planar continuous YIG film, consistent with the results of the measured hysteresis loop. Tunable line width broadening has been confirmed independently by propagating spin-wave spectroscopy, where unidirectional spin waves are detected. Position-dependent BLS measurement unravels an oscillating-like behavior of magnon populations in Co nanowire grating, which might result from the magnon trap effect. These results are thus attractive for reconfigurable nanomagnonics devices.

As the core of spintronics, the transport of spin aims at a low-dissipation data process. The pure spin current transmission carried by magnons in antiferromagnetic insulators is natively endowed with superiority such as long-distance propagation and ultrafast speed. However, the traditional control of magnon transport in an antiferromagnet via a magnetic field or temperature variation adds critical inconvenience to practical applications. Controlling magnon transport by electric methods is a promising way to overcome such embarrassment and to promote the development of energy-efficient antiferromagnetic logic. Here, the experimental realization of an electric field-induced piezoelectric strain-controlled magnon spin current transmission through the antiferromagnetic insulator in the Y

In this work, we demonstrate that pure three-dimensional honeycomb-like porous carbons (3D-HPC) can be prepared by one-step simultaneous carbonization and activation of Ganoderma lucidum spores (GLS) with KOH active agent. Benefiting from the specific natural morphology of GLS and uniform activation process, the obtained 3D-HPC exhibits pure honeycomb-like hierarchical structures. The obtained 3D-HPC-900 shows the honeycomb-like structures and a high density of narrow mesopores, leading to a high accessible surface area. Combined with high specific surface area of 1995 m2 g−1 and oxygen/nitrogen doping, 3D-HPC-900 exhibits a high specific capacitance of 224 F g−1 at a current density of 0.25 A g−1, an ultrahigh capacitance retention of 75.9% even the current density increased by 80 times, and an excellent cycling stability with 100% capacitance retention after 50,000 cycles. More importantly, the maximum energy density can reach up to 75.7 W h kg−1 at the power density of 1750 W kg−1 in ionic liquid. Meanwhile, the experimental results clearly reveal the exclusive effects of mesopores on improving the rate performance in electrochemical capacitors. Therefore, the work provides a clear method on preparation of high-valued honeycomb-like structured carbon materials to enhance the rate capability of carbon-based electrochemical capacitors.

Magnetoresistance effects are used in a variety of devices including hard disk drives and magnetic random access memories. In particular, giant magnetoresistance and tunnelling magnetoresistance can be used to create spin valves and tunnel junctions in which the resistance depends on the relative magnetization orientations of two ferromagnetic conducting layers. Here, we report a magnetoresistance effect that occurs in a platinum layer deposited on a magnon junction consisting of two insulating magnetic yttrium iron garnet (YIG) layers separated by an antiferromagnetic nickel oxide spacer layer. The resistance of the platinum layer is found to depend on the magnetization of the YIG layer in direct contact with it (an effect known as spin Hall magnetoresistance), but also the magnetization of the adjacent YIG layer in the junction. The resistance of the platinum layer is higher when the two YIG layers are aligned antiparallel than when parallel. We assign this behaviour to a magnonic nonlocal spin Hall magnetoresistance in which spin-carrying magnon propagation across the junction affects spin accumulation at the metal interface and hence modulates the spin Hall magnetoresistance. The effect could be used to develop spintronic and magnonic devices that have spin transport properties controlled by an all-insulating magnon junction and are thus free from Joule heating. A magnetoresistance effect that occurs in a platinum layer deposited on a magnon junction consisting of two insulating magnetic yttrium iron garnet layers separated by an antiferromagnetic nickel oxide spacer layer could be used to create spintronic and magnonic devices that are free from Joule heating.

Our previous study has indicated that cancer-associated fibroblasts (CAFs) play a crucial role in regulating gemcitabine resistance through transferring exosomal miRNA-106b to cancer cells. Tumor-associated macrophages (TAMs) are recently verified to facilitate gemcitabine resistance. However, the effect of CAFs in regulating TAMs function in pancreatic cancer (PCa) remains unclear. Here, primary CAFs were extracted from tumor tissues of PCa patients, and CAFs-derived exosomes (CAFs-Exo) were acquired and authenticated by transmission electron microscopy, qNano, and western blot analysis. The role of exosomal miRNA-320a in facilitating macrophage M2 polarization was investigated in vitro. We found that CAFs-derived conditioned medium (CM) possessed a higher potential to promote macrophage M2 polarization compared with normal fibroblasts (NFs) or PCa cell-derived CM. Furthermore, CAFs-Exo treatment polarized macrophage to M2 phenotype. miRNA-320a levels were remarkably increased in CAFs-Exo versus NFs-Exo. More important, miRNA-320a could be transferred from CAFs to macrophages through exosomes, and miRNA-320a overexpression in macrophages facilitated its M2 polarization. Functionally, miRNA-320a-overexpressed macrophages facilitated PCa cell proliferation and invasion. CAFs pretreated with miRNA-320a inhibitor reduced miRNA-320a expression in CAFs-Exo and led to decreased M2 macrophage polarization. Finally, we verified that miRNA-320a polarized macrophage to M2 phenotype by regulating PTEN/PI3Kγ signaling. Taken together, the current data demonstrated that CAFs-derived exosomal miRNA-320a facilitated macrophage M2 polarization to accelerate malignant behavior of PCa cells.

The interlayer coupling of two ferromagnetic layers results in found of giant magnetoresistance, which forms the foundation of spintronics and accelerates the development of information technology. Compared with ferromagnets, antiferromagnets (AFMs) possess huge potential in ultrafast and high-density data processing and information storage because of their terahertz spin dynamics and subtle stray field. The interlayer coupling in AFMs has long been neglected, because the collinear parallel and antiparallel arrangements of AFMs are indistinguishable. However, the noncollinear interlayer coupling in AFMs is detectable, and can be a potential candidate for practical antiferromagnetic spintronic devices. Here we demonstrate orthogonal interlayer coupling at room temperature in an all-antiferromagnetic junction Fe2O3/Cr2O3/Fe2O3, where the Néel vectors in the top and bottom functional materials Fe2O3 are strongly orthogonally coupled and the coupling strength of which is significantly affected by the thickness of the antiferromagnetic Cr2O3 spacer. From the energy and symmetry analysis, the direct coupling via uniform magnetic ordering is excluded. The coupling is proposed to be mediated by quasi-long range order in the spacer. Besides the fundamental significance, the strong coupling in an antiferromagnetic junction makes it a promising building block for practical antiferromagnetic spintronics with high-speed operation and ultrahigh-density integration.

In conventional ferromagnet/spacer/ferromagnet sandwiches, noncollinear couplings are commonly absent because of the low coupling energy and strong magnetization. For antiferromagnets (AFM), the small net moment can embody a low coupling energy as a sizable coupling field, however, such AFM sandwich structures have been scarcely explored. Here we demonstrate orthogonal interlayer coupling at room temperature in an all-antiferromagnetic junction Fe2O3/Cr2O3/Fe2O3, where the Néel vectors in the top and bottom Fe2O3 layers are strongly orthogonally coupled and the coupling strength is significantly affected by the thickness of the antiferromagnetic Cr2O3 spacer. From the energy and symmetry analysis, the direct coupling via uniform magnetic ordering in Cr2O3 spacer in our junction is excluded. The coupling is proposed to be mediated by the non-uniform domain wall state in the spacer. The strong long-range coupling in an antiferromagnetic junction provides an unexplored approach for designing antiferromagnetic structures and makes it a promising building block for antiferromagnetic devices.

Magnon transfer torque (MTT) is regarded as capable of manipulating spin by magnons or spin waves only without spatial movement of electrons, which is a key to enrich the toolbox for magnonics. Here using a magnon current through an antiferromagnetic NiO spacer, which can be deep into a magnetic insulator ${\mathrm{Y}}_{3}{\mathrm{Fe}}_{5}{\mathrm{O}}_{12}$ (YIG), we demonstrated the perpendicular magnetization of the YIG in a YIG/NiO/Pt heterostructure could be switched. When the thickness of the magnon channel NiO was 1.5 nm, the magnon current could still maintain about $84%$ of the spin current for the YIG/Pt control device, indicating high efficiency of the NiO spacer in transferring magnon torque. Switching the perpendicular magnetization in the YIG/NiO/Pt heterostructures unambiguously verified the effect of magnon transfer torque (MTT), which may advance the development of magnonic memories and logics.

An experimental study of the phenomenon of electric current influence on the value and orientation of the exchange bias field (HEB) in the Pt/Co/NiO structure is carried out. Depending on the direction of the magnetization in a ferromagnet (FM) layer and the current pulse amplitude, the value of the HEB field can be changed repeatedly in the range of ±7.5 mT. A few experiments are performed to separate the contributions from two current-induced effects: (i) an injection of the spin current into an antiferromagnet layer (AFM) and (ii) Joule heating. As a result, we conclude that the modification in the HEB field during current pulse transmission in the Pt/Co/NiO structure is due to heating and the low value of Neel temperature (TN = 162 °C). This fact explains the absence of the exchange bias effect on the spin-orbit torque (SOT)-assisted magnetization switching. The most striking observation to emerge from the experimental data analysis is that depending on the initial spin configuration of the domain structure in the FM layer and the current pulse amplitude, the exchange bias can be changed locally. This opens up prospects for creating exchange-coupled FM/AFM structures with dynamically tuned parameters of the exchange bias, which can be used for the development of magnetic memory, neuromorphic, and logic devices based on magnetic nanosystems.

Creating perpendicular fields by spin-orbit torques (SOTs) is an effective way to realize field-free and highly efficient SOT switching for magnetic films with perpendicular magnetic anisotropy (PMA). Here, (1) using a magnetic trilayer composed of a layer with PMA, a spacer, and a layer with in-plane magnetic anisotropy; and (2) by injecting spin currents with the same polarization into the two magnetic layers, we can generate the desired effective perpendicular field through SOT and further utilize this effective field to assist in field-free SOT switching. The SOT efficiency to produce the perpendicular field reaches $2.1\phantom{\rule{0.2em}{0ex}}\mathrm{Oe}/{10}^{10}\phantom{\rule{0.2em}{0ex}}{\mathrm{Am}}^{\ensuremath{-}2}$. This study can be instructive for designing energy-efficient SOT magnetic random-access memories.

In this work, we demonstrate a novel strategy for producing a porous carbon hollow rod (PCHR) via simple carbonization of magnesium gluconate. The mass ratios of PCHR/KOH are a key factor in direct...

Objective We aimed to investigate the symptoms of inpatients with bipolar disorder (BD) in different types of families, and to explore the correlations between family coherence, family adaptability, and family functioning among inpatients with BD. Methods Inpatients with BD in Hebei, China (n = 61; mean age = 33.85±10.54; 39 males) participated in this study. Participants’ symptoms were evaluated using the Bech–Rafaelsen Mania Scale (BRMS) and Hamilton Depression Rating Scale (HDRS) at weeks 1, 4, and 8 after their admission to the hospital. Participants’ family type was assessed using the Family Adaptability and Cohesion Scale II–Chinese Version. Family functioning was assessed using Family Assessment Device. Results Participants were classified into three family types: balanced (n = 13), mid-range (n = 28), and extreme (n = 20). BRMS scores improved over time in patients from all three family types. Improvement was slightly better with the balanced than the extreme family type. HDRS scores showed an improving trend over time, although this was not significant. Family coherence, adaptability, and functioning were mutually correlated. Conclusion The family system and family functioning are important factors that clinicians should keep in mind when treating people with BD.

Our previous study has indicated that cancer-associated fibroblasts (CAFs) play a crucial role in regulating gemcitabine resistance through transferring exosomal miRNA-106b to cancer cells. Tumor-associated macrophages (TAMs) are recently verified to facilitate gemcitabine resistance. However, the effect of CAFs in regulating TAMs function in pancreatic cancer (PCa) remains unclear. Here, primary CAFs were extracted from tumor tissues of PCa patients, and CAFs-derived exosomes (CAFs-Exo) were acquired and authenticated by transmission electron microscopy, qNano, and western blot analysis. The role of exosomal miRNA-320a in facilitating macrophage M2 polarization was investigated

Atomoxetine (ATX), a selective and potent inhibitor of the presynaptic norepinephrine transporter, is used mainly to treat attention-deficit hyperactivity disorder. Although multiple adverse effects associated with ATX have been reported including severe liver injuries, the mechanisms of ATX-related toxicity remain largely unknown. Metabolism frequently contributes to adverse effects of a drug through reactive metabolites, and the bioactivation status of ATX is still not investigated yet. Here, we systematically investigated ATX metabolism, bioactivation, species difference in human, mouse, and rat liver microsomes (HLM, MLM, and RLM) and in mice using metabolomic approaches as mice and rats are commonly used animal models for the studies of drug toxicity. We identified thirty one ATX metabolites and adducts in LMs and mice, 16 of which are novel. In LMs , we uncovered two methoxyamine-trapped aldehydes, two cyclization metabolites, detoluene-ATX, and ATX-N-hydroxylation for the first time. Detoluene-ATX and one cyclization metabolite were also observed in mice. Using chemical inhibitors and recombinant CYP enzymes, we demonstrated that CYP2C8 and CYP2B6 mainly contribute to the formation of aldehyde; CYP2D6 is the dominant enzyme for the formation of ATX cyclization and detoluene-ATX; CYP3A4 is major enzyme responsible for the hydroxylamine formation. The findings concerning aldehydes should be very useful to further elucidate the mechanistic aspects of adverse effects associated with ATX from metabolic angles. Additionally, the species differences for each metabolite should be helpful to investigate the contribution of specific metabolites to ATX toxicity and possible drug-drug interactions in suitable models.

Recently the anomalous Hall effect was predicted as a possible mechanism to produce magnetization-dependent spin current. Here we have applied NiFe/Ru/perpendicular magnetic multilayers and a specific geometry to demonstrate magnetization switching driven by anomalous spin-orbit torque resulting from the bulk anomalous Hall effect. The anomalous spin Hall torque of NiFe is strong enough not only to switch the magnetization of perpendicular Co but also leads to opposite switching chirality compared with the ordinary spin Hall torque. This work confirmed the existence of a strong anomalous spin Hall torque due to anomalous Hall effect, which may lay a foundation to develop spin-orbit torque devices free of heavy metals.

Magnonics as an emerging frontier of spintronics aims using magnons to deliver information free from electron scattering and as-induced Joule heating. In general, magnon currents can be excited both thermally and electrically in magnetic insulators by applying a current in an adjacent heavy-metal layer. Here, we report another kind of magnon junctions (MJs) composed of Y3Fe5O12/CoO/ Y3Fe5O12 heterostructures, in which Y3Fe5O12 and CoO are, respectively, ferrimagnetic and antiferromagnetic insulators. A temperature gradient can drive a high (low) magnon current via the spin Seebeck effect when the Y3Fe5O12 layers in an MJ are configured at the parallel (antiparallel) state, showing a spin valve-like behavior. Electrically injected magnon current could also be controlled by the MJs, contributing to a magnon-mediate nonlocal spin Hall magnetoresistance (SMR). Furthermore, compared with its NiO counterpart, both the magnon junction and magnon-mediate SMR effects can be clearly observed at room temperature for the CoO-based magnon junctions, which can possibly be applied as a building block for room-temperature magnon-based memory or logic devices.

Spin logics provide a shortcut toward logic-in-memory architectures. Here, using a T-type magnetic stack with a perpendicular magnetic layer, an in-plane layer, and a spacing layer in between, we can switch both the in-plane and perpendicular layers and independently control their magnetization without an external magnetic field. By initializing magnetization of the in-plane layer, we can further control chirality (clockwise and counterclockwise) of the current-dependence of perpendicular magnetization. Based on these properties and the majority gate theory, we experimentally construct five Boolean logic gates in a single device in the desired field-free condition, which steps forward to practical spin–orbit torque logics.

Spin waves are considered as a promising candidate for next-generation logic devices with low power dissipation. Exchange spin waves are particularly attractive for high-speed data processing and scaling down the size of magnonic logic devices. Here, we achieve the excitation of short-wavelength propagating spin waves with wavelengths as short as 45 nm in a 20 nm-thick yttrium iron garnet film covered by 70 nm-wide Co25Fe75 nanowires with low magnetic damping and high saturation magnetization, and the ferromagnetic resonance of Co25Fe75 nanowires is excited by a 200 nm-wide nano-strip line. From our measurements, we extrapolate a group velocity for exchange spin waves of up to 1.9 km/s close to the zero magnetic field (0.5 mT).

Magnetic two-dimensional (2D) van der Waals (vdWs) materials are receiving increased attention due to their exceptional properties and potential applications in spintronic devices. Because exchange bias and spin–orbit torque (SOT)-driven magnetization switching are basic ingredients for spintronic devices, it is of pivotal importance to demonstrate these effects in the 2D vdWs material-based magnetic heterostructures. In this work, we employ a vacuum exfoliation approach to fabricate Fe3GeTe2 (FGT)/Ir22Mn78 (IrMn) and FGT/Pt bilayers, which have high-quality interfaces. An out-of-plane exchange bias of up to 895 Oe is obtained in the former bilayer, which is larger than that of the previously studied bilayers. In the latter bilayer, the SOT switching of the perpendicularly magnetized FGT is realized, which exhibits higher SOT-driven switching performance compared to the previously studied FGT/Pt bilayer devices with interfacial oxidation. The minimum of SOT efficiency is further determined to be 0.18 ± 0.04, comparable to the previously reported values for the Pt/Co and Pt/CoFeB bilayers. This work highlights the importance of the high-quality interface for the exchange bias and SOT effect and may pave the way for implementing 2D vdWs in spintronic devices.

We show that a trilayer magnetic structure, consisting of a heavy metal (Platinum) as a buffer, an ultrathin ferromagnet (Cobalt) as a functional layer, and an antiferromagnetic insulator (Nickel oxide, NixOy) as a capping, is a host of intriguing physical phenomena desirable for spintronics. X-ray photoelectron spectroscopy revealed changes in the ratio of NixOy phases with different stoichiometry. Due to strong spin–orbit coupling, the Pt layer induces perpendicular magnetic anisotropy in Co, breaks its structural inversion symmetry, and causes an additive effect of Pt/Co and Co/NixOy interfaces to the effective interfacial Dzyaloshinskii-Moriya interaction (Deff). Manipulation the magnetic anisotropy can be realized by the ferromagnetic layer thickness variation and modification of the Co/NixOy interface. The NixOy capping layer induces the exchange bias in Co, which effective field |Beb| can be controlled in the range from 0 to 24 mT. The magnitude and direction of Beb does not affect Deff. The increase of Ar pressure leads to structural transformation of the Co/NixOy interface and, consequently, to decrease of the surface Dzyaloshinskii-Moriya interaction (Ds), the source of which is the NiO phase. We demonstrate that the studied Pt/Co/NixOy system has a number of functional properties useful for future logic and memory applications.

Agomelatine (AGM), an analog of melatonin, is a potential agonist at melatonin receptors 1/2 and a selective antagonist at 5-hydroxytryptamine 2C receptors. AGM is widely used for the treatment of major depressive episodes in adults. However, multiple adverse effects associated with AGM have been reported in clinical practice. It is little known about AGM metabolism in vitro and in vivo, although metabolism plays a pivotal role in its efficacy and safety. To elucidate metabolic pathways of AGM, we systemically investigated AGM metabolism and its bioactivation in human liver microsomes (HLM) and mice using metabolomic approaches. We identified thirty-eight AGM metabolites and adducts, among which thirty-two are novel. In HLM, we uncovered five GSH-trapped adducts and two semicarbazide-trapped aldehydes. Moreover, we characterized three N-acetyl cysteine conjugated-AGM adducts in mouse urine and feces, which were formed from the degradation of AGM_GSH adducts. Using recombinant CYP450 isoenzymes and chemical inhibitors, we demonstrated that CYP1A2 and CYP3A4 are primary enzymes contributing to the formation of AGM_GSH adducts and AGM_hydrazones. This study provided a global view of AGM metabolism and identified the novel pathways of AGM bioactivation, which could be utilized for further understanding the mechanism of adverse effects related to AGM and possible drug-drug interactions.

Imaging hydrogen sulfide (H2S) at the subcellular resolution will greatly improve the understanding of functions of this signaling molecule. Taking advantage of the protein labeling technologies, we report a general strategy for the development of organelle specific H2S probes, which enables sub-cellular H2S imaging essentially in any organelles of interest.

Aims: Quantitative imaging of glutathione (GSH) with high spatial and temporal resolution is essential for studying the roles of GSH in redox biology. To study the long-standing question of compartmentalization of GSH, especially its distribution between the nucleus and cytosol, an organelle-targeted quantitative probe is needed. Results: We developed a reversible reaction-based ratiometric fluorescent probe—HaloRT—that can quantitatively measure GSH dynamics with subcellular resolution in real time. Using HaloRT, we quantitatively measured the GSH concentrations in the nucleus and cytosol of HeLa cells and primary hepatocytes under different treatment conditions and found no appreciable concentration gradients between these two organelles. Innovation and Conclusion: We developed the first reversible ratiometric GSH probe that can be universally targeted to any organelle of interest. Taking advantage of this new tool, we provided definitive evidence showing that GSH concentrations are not significantly different between the nucleus and cytosol, challenging the view of nuclear compartmentalization of GSH.

Aims: Quantitative imaging of glutathione with high spatial and temporal resolution is essential for studying the roles of glutathione in redox biology. To study the long-standing question of compartmentalization of glutathione, especially its distribution between the nucleus and the cytosol, an organelle-targeted quantitative probe is needed. Results: We developed a reversible reaction-based ratiometric fluorescent probe, HaloRT, that can quantitatively measure glutathione dynamics with subcellular resolution in real-time. Using HaloRT, we quantitatively measured the glutathione concentrations in the nucleus and the cytosol of HeLa cells and primary hepatocytes under different treatment conditions and found no appreciable concentration gradients between these two organelles. Innovation and conclusion: We developed the first reversible ratiometric glutathione probe that can be universally targeted to any organelles of interest. Taking advantage of this new tool, we provided a definitive evidence showing that glutathione concentrations are not significantly different between the nucleus and the cytosol, challenging the view of nuclear compartmentalization of glutathione.

Glutathione (GSH) plays an important role in maintaining redox homeostasis inside cells. Currently, there are no methods available to quantitatively assess the GSH concentration in live cells. Live cell fluorescence imaging revolutionized the field of cell biology and has become an indispensable tool in current biological studies. In order to minimize the disturbance to the biological system in live cell imaging, the probe concentration needs to be significantly lower than the analyte concentration. Because of this, any irreversible reaction-based GSH probe can only provide qualitative results within a short reaction time and will exhibit maximum response regardless of the GSH concentration if the reaction is completed. A reversible reaction-based probe with an appropriate equilibrium constant allows measurement of an analyte at much higher concentrations and, thus, is a prerequisite for GSH quantification inside cells. In this contribution, we report the first fluorescent probe—ThiolQuant Green (TQ Green)—for quantitative imaging of GSH in live cells. Due to the reversible nature of the reaction between the probe and GSH, we are able to quantify mM concentrations of GSH with TQ Green concentrations as low as 20 nM. Furthermore, the GSH concentrations measured using TQ Green in 3T3-L1, HeLa, HepG2, PANC-1, and PANC-28 cells are reproducible and well correlated with the values obtained from cell lysates. TQ Green imaging can also resolve the changes in GSH concentration in PANC-1 cells upon diethylmaleate (DEM) treatment. In addition, TQ Green can be conveniently applied in fluorescence activated cell sorting (FACS) to measure GSH level changes. Through this study, we not only demonstrate the importance of reaction reversibility in designing quantitative reaction-based fluorescent probes but also provide a practical tool to facilitate redox biology studies.

Two-dimensional layered materials with remarkable thermoelectric coefficients are promising candidates for sustainable thermopower batteries. Here, we investigate the anomalous Nernst effect and anomalous Hall effect in the polycrystalline Fe 3 GeTe 2 thin films. While its Seebeck coefficient and anomalous Hall angle (or magnetization) monotonously increase and decrease with temperature, respectively, the anomalous Nernst coefficient of the Fe 3 GeTe 2 films exhibits a peak value of 0.28 μV K–1 T–1 at 150 K, which is the compromised outcome between the enhanced Seebeck effect and the gradually weakened magnetism with elevating temperature. A noticeable anomalous Nernst effect observed in Fe 3 GeTe 2 sheds light on the low-temperature application of two-dimensional layered materials in spin-caloritronics.

All electrical manipulation of magnetization in an Y3Fe5O12 (YIG)/Pt system was crucial to develop magnon-based spintronic devices. In this study, we realized spin–orbit torque (SOT) switching in perpendicular YIG/Pt films. Perpendicular magnetic anisotropy of YIG was induced by strain from the bottom substrate and also influenced by the capping Pt layer and subsequent annealing. Besides, SOT efficiency of the YIG/Pt system was also measured. Damping-like torque with an efficiency of 0.98 Oe/(MA/cm2) was the dominating term to contribute to the SOT switching. This work was beneficial to construct electrically controllable magnon devices.

Phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] is a low-abundance phosphoinositide presumed to be localized to endosomes and lysosomes, where it recruits cytoplasmic peripheral proteins and regulates endolysosome-localized membrane channel activity. Cells lacking PI(3,5)P2 exhibit lysosomal trafficking defects, and human mutations in the PI(3,5)P2-metabolizing enzymes cause lysosome-related diseases. The spatial and temporal dynamics of PI(3,5)P2, however, remain unclear due to the lack of a reliable detection method. Of the seven known phosphoinositides, only PI(3,5)P2 binds, in the low nanomolar range, to a cytoplasmic phosphoinositide-interacting domain (ML1N) to activate late endosome and lysosome (LEL)-localized transient receptor potential Mucolipin 1 (TRPML1) channels. Here, we report the generation and characterization of a PI(3,5)P2-specific probe, generated by the fusion of fluorescence tags to the tandem repeats of ML1N. The probe was mainly localized to the membranes of Lamp1-positive compartments, and the localization pattern was dynamically altered by either mutations in the probe, or by genetically or pharmacologically manipulating the cellular levels of PI(3,5)P2. Through the use of time-lapse live-cell imaging, we found that the localization of the PI(3,5)P2 probe was regulated by serum withdrawal/addition, undergoing rapid changes immediately before membrane fusion of two LELs. Our development of a PI(3,5)P2-specific probe may facilitate studies of both intracellular signal transduction and membrane trafficking in the endosomes and lysosomes.

Protein-protein interactions (PPIs) play a central role in most biological processes, and therefore represent an important class of targets for therapeutic development. However, disrupting PPIs using small-molecule inhibitors (SMIs) is challenging and often deemed as "undruggable." We developed a cell-based functional assay for high-throughput screening to identify SMIs for steroid receptor coactivator-3 (SRC-3 or AIB1), a large and mostly unstructured nuclear protein. Without any SRC-3 structural information, we identified SI-2 as a highly promising SMI for SRC-3. SI-2 meets all of the criteria of Lipinski's rule [Lipinski et al. (2001) Adv Drug Deliv Rev 46(1-3):3-26] for a drug-like molecule and has a half-life of 1 h in a pharmacokinetics study and a reasonable oral availability in mice. As a SRC-3 SMI, SI-2 can selectively reduce the transcriptional activities and the protein concentrations of SRC-3 in cells through direct physical interactions with SRC-3, and selectively induce breast cancer cell death with IC50 values in the low nanomolar range (3-20 nM), but not affect normal cell viability. Furthermore, SI-2 can significantly inhibit primary tumor growth and reduce SRC-3 protein levels in a breast cancer mouse model. In a toxicology study, SI-2 caused minimal acute cardiotoxicity based on a hERG channel blocking assay and an unappreciable chronic toxicity to major organs based on histological analyses. We believe that this work could significantly improve breast cancer treatment through the development of "first-in-class" drugs that target oncogenic coactivators.

A fundamental question regarding autophagosome formation is how the shape of the double-membrane autophagosomal vesicle is generated. Here we show that in mammalian cells assembly of an actin scaffold inside the isolation membrane (the autophagosomal precursor) is essential for autophagosomal membrane shaping. Actin filaments are depolymerized shortly after starvation and actin is assembled into a network within the isolation membrane. When formation of actin puncta is disrupted by an actin polymerization inhibitor or by knocking down the actin-capping protein CapZβ, isolation membranes and omegasomes collapse into mixed-membrane bundles. Formation of actin puncta is PtdIns(3)P dependent, and inhibition of PtdIns(3)P formation by treating cells with the PI(3)K inhibitor 3-MA, or by knocking down Beclin-1, abolishes the formation of actin puncta. Binding of CapZ to PtdIns(3)P, which is enriched in omegasomes, stimulates actin polymerization. Our findings illuminate the mechanism underlying autophagosomal membrane shaping and provide key insights into how autophagosomes are formed.

Disulfide has been the only widely used functionality to serve as a reduction responsive trigger in drug delivery. We introduce thioester as a novel thiol responsive chemistry for drug delivery, whose reactivity can be conveniently modulated by choosing the appropriate steric environment around the thioester. Compared with disulfides, thioesters are facile to synthesize and have an order of magnitude broader kinetic tunability. A novel traceless reversible protein PEGylation reagent is developed based on thioester chemistry.