Gut microbiota affects sensitivity to immune-mediated isoniazid-induced liver injury.

Isoniazid (INH) is a highly effective single and/or combined first-line anti-tuberculosis (anti-TB) therapy drug, and the hepatotoxicity greatly limits its clinical application. INH-induced liver injury (INH-DILI) is a typical immune-mediated idiosyncratic drug-induced liver injury. Existing mechanisms including genetic variations in drug metabolism and immune responses cannot fully explain the differences in susceptibility and sensitivity to INH-DILI, suggesting that other factors may be involved. Accumulating evidence indicates that the development and severity of immune-mediated liver injury is related to gut microbiota. In this study, INH exposure caused liver damage, immune disregulation and microbiota profile alteration. Depletion of gut microbiota ameliorated INH-DILI, and improved INH-DILI-associated immune disorder and inflammatory response. Moreover, hepatotoxicity of INH was ameliorated by fecal microbiota transplantation (FMT) from INH-treated mice. Notably, Bifidobacterium abundance was significantly associated with transaminase levels. In conclusion, our results suggested that the effect of gut microbiota on INH-DILI was related to immunity, and the difference in INH-DILI sensitivity was related to the structure of gut microbiota. Changes in the structure of gut microbiota by continuous exposure of INH resulted in the tolerance to liver injury, and probiotics such as Bifidobacterium might play an important role in INH-DILI and its "adaptation" phenomenon. This work provides novel evidence for elucidating the underlying mechanism of difference in individual's response to INH-DILI and potential approach for intervening anti-TB drug liver injury by modulating gut microbiota.

Quantum criticality of excitonic Mott metal-insulator transitions in black phosphorus.

Quantum phase transition refers to the abrupt change of ground states of many-body systems driven by quantum fluctuations. It hosts various intriguing exotic states around its quantum critical points approaching zero temperature. Here we report the spectroscopic and transport evidences of quantum critical phenomena of an exciton Mott metal-insulator-transition in black phosphorus. Continuously tuning the interplay of electron-hole pairs by photo-excitation and using Fourier-transform photo-current spectroscopy as a probe, we measure a comprehensive phase diagram of electron-hole states in temperature and electron-hole pair density parameter space. We characterize an evolution from optical insulator with sharp excitonic transition to metallic electron-hole plasma phases featured by broad absorption and population inversion. We also observe strange metal behavior that resistivity is linear in temperature near the Mott transition boundaries. Our results exemplify an ideal platform to investigating strongly-correlated physics in semiconductors, such as crossover between superconductivity and superfluity of exciton condensation.

Atomic-Scale Confinement and Negative Refraction of Plasmons by Twisted Bilayer Graphene.

Moiré superlattices provide in-plane quantum restriction for light-matter interactions in twisted bilayer graphene (tBLG), leading to the exotic photon-Moiré physics and potential applications for light manipulation. Recently, our experiment identified a highly confined slow surface plasmons polaritons (SPPs) mode in tBLG. Here, we demonstrate that the propagation of the slow SPPs mode in tBLG is spatially tailored and steered at deep subwavelengths. Analysis by the perturbation theory indicates that the coupling between the slow SPPs mode and the Moiré system is greatly strengthened, which regulates the wavefront at the atomic scale and makes tBLG serve as a universal optical metamaterial. Consequently, the negative refraction is achieved at the interface of monolayer graphene and tBLG, by which a metalens with a controllable focal length and an extremely high resolution up to 1/150 of wavelength is devised. Our work paves the way for constructing optical metamaterial at the atomic scale and develops future photon-Moiré interaction systems.

Observation of chiral and slow plasmons in twisted bilayer graphene.

Moiré superlattices have led to observations of exotic emergent electronic properties such as superconductivity and strong correlated states in small-rotation-angle twisted bilayer graphene (tBLG)1,2. Recently, these findings have inspired the search for new properties in moiré plasmons. Although plasmon propagation in the tBLG basal plane has been studied by near-field nano-imaging techniques3-7, the general electromagnetic character and properties of these plasmons remain elusive. Here we report the direct observation of two new plasmon modes in macroscopic tBLG with a highly ordered moiré superlattice. Using spiral structured nanoribbons of tBLG, we identify signatures of chiral plasmons that arise owing to the uncompensated Berry flux of the electron gas under optical pumping. The salient features of these chiral plasmons are shown through their dependence on optical pumping intensity and electron fillings, in conjunction with distinct resonance splitting and Faraday rotation coinciding with the spectral window of maximal Berry flux. Moreover, we also identify a slow plasmonic mode around 0.4 electronvolts, which stems from the interband transitions between the nested subbands in lattice-relaxed AB-stacked domains. This mode may open up opportunities for strong light-matter interactions within the highly sought after mid-wave infrared spectral window8. Our results unveil the new electromagnetic dynamics of small-angle tBLG and exemplify it as a unique quantum optical platform.

A novel solid phase extraction sample preparation method for sensitively determining doxepin and N-nordoxepin in human plasma and its application in a bioequivalence study in healthy Chinese volunteers.

Doxepin, a tricyclic antidepressant (TCA), is widely used in the treatment of depressive disorder and anxiety. There are some liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods that have been reported for detecting doxepin, but inadequacies in recovery and cumbersome sample preparation obstruct the pharmacokinetics study. Therefore, we aimed to develop and validate a rapid sample preparation method based on solid-phase extraction (SPE) for the precise quantification of doxepin and its metabolites. Chromatography separation was performed on a Waters ACQUITY UPLC BEH C18 column (2.1 × 100 mm, 1.7 µm) and a mobile phase consisting of 70% of mobile phase A (0.1% formic acid and 10 mM ammonium formate) and 30% mobile phase B (0.1% formic acid in acetonitrile) at a flow rate of 0.4 mL min-1 in the step gradient elution conditions. The lower limits of quantification for doxepin and N-nordoxepin were 4 pg mL-1 and 2 pg mL-1, respectively. This method was validated with satisfactory results including good precision and accuracy. A rapid, sensitive, and specific LC-MS/MS method was developed and validated for the determination of doxepin in human plasma. This method could be applied for determining doxepin and N-nordoxepin concentrations in plasma that could be useful for bioequivalence study of 3 mg doxepin.

Trimethylamine N-Oxide Exacerbates Renal Inflammation and Fibrosis in Rats With Diabetic Kidney Disease.

The gut microbiota plays a pivotal role in the onset and development of diabetes and its complications. Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite of certain nutrients, is associated with type 2 diabetes and its complications. Diabetic kidney disease (DKD) is one of the most serious microvascular complications. However, whether TMAO accelerates the development of DKD remains unclear. We tested the hypothesis that TMAO accelerates the development of DKD. A high-fat diet/low-dose streptozotocin-induced diabetes rat model was established, with or without TMAO in the rats' drinking water. Compared to the normal rats, the DKD rats showed significantly higher plasma TMAO levels at the end of the study. TMAO treatment not only exacerbated the kidney dysfunction of the DKD rats, but also renal fibrosis. Furthermore, TMAO treatment activated the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome and resulted in the release of interleukin (IL)-1ß and IL-18 to accelerate renal inflammation. These results suggested that TMAO aggravated renal inflammation and fibrosis in the DKD rats, which provides a new perspective to understand the pathogenesis of DKD and a potential novel target for preventing the progression of DKD.

The efficacy and toxicity of antineoplastic antimetabolites: Role of gut microbiota.

The incidence and mortality of cancer are rapidly growing all over the world. Nowadays, antineoplastic antimetabolites still play a key role in the chemotherapy of cancer. However, the interindividual variations in the efficacy and toxicity of antineoplastic antimetabolites are nonnegligible challenges to their clinical applications. Although many studies have focused on genetic variation, the reasons for these interindividual variations have still not been fully understood. Gut microbiota is reported to be associated with the efficacy and toxicity of antineoplastic antimetabolites. In this review, we summarize the interaction of antineoplastic antimetabolites on gut microbiota and the influences of shifted gut microbiota profiles on the efficacy and toxicity of antineoplastic antimetabolites. The factors affecting the efficacy and toxicity of antineoplastic antimetabolites via gut microbiota are also discussed. In addition, we present our viewpoints that regulating the gut microbiota may increase the efficacy and decrease the toxicity of antineoplastic antimetabolites. This will help us better understand the new mechanism via gut microbiota and promote individualized use of antineoplastic antimetabolites.

Roles of Gut Microbial Metabolites in Diabetic Kidney Disease.

Diabetes is a highly prevalent metabolic disease that has emerged as a global challenge due to its increasing prevalence and lack of sustainable treatment. Diabetic kidney disease (DKD), which is one of the most frequent and severe microvascular complications of diabetes, is difficult to treat with contemporary glucose-lowering medications. The gut microbiota plays an important role in human health and disease, and its metabolites have both beneficial and harmful effects on vital physiological processes. In this review, we summarize the current findings regarding the role of gut microbial metabolites in the development and progression of DKD, which will help us better understand the possible mechanisms of DKD and explore potential therapeutic approaches for DKD.

Monolithic Full-Stokes Near-Infrared Polarimetry with Chiral Plasmonic Metasurface Integrated Graphene-Silicon Photodetector.

The ability to detect the full-Stokes polarization of light is vital for a variety of applications that often require complex and bulky optical systems. Here, we report an on-chip polarimeter comprising four metasurface-integrated graphene-silicon photodetectors. The geometric chirality and anisotropy of the metasurfaces result in circular and linear polarization-resolved photoresponses, from which the full-Stokes parameters, including the intensity, orientation, and ellipticity of arbitrarily polarized incident infrared light (1550 nm), can be obtained. The design presents an ultracompact architecture while excluding the standard bulky optical components and structural redundancy. Computational extraction of full-Stokes parameters from mutual information among four detectors eliminates the need for a large absorption contrast between different polarization states. Our monolithic plasmonic metasurface integrated polarimeter is ideal for a variety of polarization-based applications including biological sensing, quantum information processing, and polarization photography.

Low Voltage Operating 2D MoS2 Ferroelectric Memory Transistor with Hf1-xZrxO2 Gate Structure.

Ferroelectric field effect transistor (FeFET) emerges as an intriguing non-volatile memory technology due to its promising operating speed and endurance. However, flipping the polarization requires a high voltage compared with that of reading, impinging the power consumption of writing a cell. Here, we report a CMOS compatible FeFET cell with low operating voltage. We engineer the ferroelectric Hf1-xZrxO2 (HZO) thin film to form negative capacitance (NC) gate dielectrics, which generates a counterclock hysteresis loop of polarization domain in the few-layered molybdenum disulfide (MoS2) FeFET. The unstabilized negative capacitor inherently supports subthermionic swing rate and thus enables switching the ferroelectric polarization with the hysteresis window much less than half of the operating voltage. The FeFET shows a high on/off current ratio of more than 107 and a counterclockwise memory window (MW) of 0.1 V at a miminum program (P)/erase (E) voltage of 3 V. Robust endurance (103 cycles) and retention (104 s) properties are also demonstrated. Our results demonstrate that the HZO/MoS2 ferroelectric memory transistor can achieve new opportunities in size- and voltage-scalable non-volatile memory applications.

Room-temperature valleytronic transistor.

Valleytronics, based on the valley degree of freedom rather than charge, is a promising candidate for next-generation information devices beyond complementary metal-oxide-semiconductor (CMOS) technology1-4. Although many intriguing valleytronic properties have been explored based on excitonic injection or the non-local response of transverse current schemes at low temperature4-7, demonstrations of valleytronic building blocks similar to transistors in electronics, especially at room temperature, remain elusive. Here, we report a solid-state device that enables a full sequence of generating, propagating, detecting and manipulating valley information at room temperature. Chiral nanocrescent plasmonic antennae8 are used to selectively generate valley-polarized carriers in MoS2 through hot-electron injection under linearly polarized infrared excitation. These long-lived valley-polarized free carriers can be detected in a valley Hall configuration9-11 even without charge current, and can propagate over 18 µm by means of drift. In addition, electrostatic gating allows us to modulate the magnitude of the valley Hall voltage. The electrical valley Hall output could drive the valley manipulation of a cascaded stage, rendering the device able to serve as a transistor free of charge current with pure valleytronic input/output. Our results demonstrate the possibility of encoding and processing information by valley degree of freedom, and provide a universal strategy to study the Berry curvature dipole in quantum materials.

Robust Impact-Ionization Field-Effect Transistor Based on Nanoscale Vertical Graphene/Black Phosphorus/Indium Selenide Heterostructures.

Maintaining the rapid development of information technology by scaling down a metal-oxide semiconductor field-effect transistor faces two serious challenges. First, the gate field loses control of the channel as it continuously decreases. Second, the fundamental thermionic limit restricts the reduction in supply voltage. Thus, further scaling down necessitates alternative device structures and different switching mechanisms. Here, we report impact-ionization transistors (IITs) based on nanoscale (∼30 nm) vertical graphene/black phosphorus (BP)/indium selenide (InSe) heterostructures. By facilitating the carrier multiplication of the ballistic impact-ionization process as the internal gain mechanism in sub-mean-free-path (sub-MFP) channels, the IITs exhibit a low average subthreshold swing (SS < 1 mV/dec) over five current levels. High stability (>10 000 cycles) and small hysteresis (<1%) switching properties are also obtained. The experimental demonstration of such transistor combining steep SS, high ON-state current density, reliable robustness, miniature footprint, and low bias voltage approaches fulfillments of targets for next-generation devices in the International Technology Roadmap for Semiconductors.

Enhanced photocatalytic properties of defect-rich α-MoO3 nanoflakes by cavitation and pitting effect.

For the first time, we present a novel, facile and eco-friendly engineering defect method, to produce defect-rich α-MoO3 (dr-MoO3) nanoflakes with abundant exposed reactive edge sites, by applying cavitation and pitting effect of high-power ultrasonic tip to inch-size α-MoO3 single crystals. The as-prepared dr-MoO3 nanoflakes deliver excellent photocatalytic activity for degradation of Rhodamine B (RhB) under visible light irradiation. The degradation apparent rate constant k of dr-MoO3 is as large as 5.9 × 10-2 min-1, which is ˜6.6 times higher than commercial α-MoO3 (com-MoO3). The superior photocatalytic performance of dr-MoO3 is attributed to its rich exposed edges and slight expansion of interlayer space, which not only enhance the adsorption of H2O and OH-, provide abundant highly reactive sites, but also shorten the distance of photogenerated carriers moving to the reactive sites. This work provides new insights into the self-enhancement of α-MoO3 photocatalytic activities, which could be extended to other layered semiconductor photocatalysts.

Rapid characterization of chlorogenic acids in Duhaldea nervosa based on ultra-high-performance liquid chromatography-linear trap quadropole-Orbitrap-mass spectrometry and mass spectral trees similarity filter technique.

Duhaldea nervosa (Wallich ex Candolle) A. Anderberg has been traditionally used as a food spice and also in folk medicine for treating traumatic injury and relieving rheumatism, especially accelerating the healing of a fracture. However, so far as we are aware, the chemical constituents have not been fully investigated. In this study, a practical method of mass spectral trees similarity filter, a data-mining technique, was developed and evaluated for the rapid detection and identification complicated constituents based on ultra-high-performance liquid chromatography-linear trap quadropole-Orbitrap-mass spectrometry. Finally, a total of 47 chlorogenic acids, including 19 monoacyl-quinic acids, 22 diacyl-quinic acids, and six triacyl-quinic acids, were unambiguously or tentatively identified based on their accurate mass measurement, chromatographic retention, MSn spectra, and bibliography data. To our best knowledge, it is the first time to report the chlorogenic acids of D. nervosa, which would be beneficial for the further material basis and quality research. Meanwhile, this mass spectral trees similarity filter method could be envisioned to exhibit a wide application for the identification of complicated components from botanical extracts.

Nanocrystalline Co0.85Se Anchored on Graphene Nanosheets as a Highly Efficient and Stable Electrocatalyst for Hydrogen Evolution Reaction.

For the first time, a porous and conductive Co0.85Se/graphene network (CSGN), constructed by Co0.85Se nanocrystals being tightly connected with each other and homogeneously anchored on few-layered graphene nanosheets, has been synthesized by a facile one-pot solvothermal method. Compared to unhybridized Co0.85Se, CSGN exhibits much faster kinetics and better electrocatalytic behavior for hydrogen evolution reaction (HER). The HER mechanism of CSGN is improved to Volmer-Tafel combination, instead of Volmer-Heyrovsky combination, for Co0.85Se. CSGN has a very low Tafel slope of 34.4 mV/dec, which is much lower than that of unhybridized Co0.85Se (41.8 mV/dec) and is the lowest ever reported for Co0.85Se-based electrocatalysts. CSGN delivers a current density of 55 mA/cm2 at 250 mV overpotential, much larger than that of Co0.85Se (33 mA/cm2). Furthermore, CSGN shows superior electrocatalytic stability even after 1500 cycles. The excellent HER performance of CSGN is attributed to the unique porous and conductive network, which can not only guarantee interconnected conductive paths in the whole electrode but also provide abundant catalytic active sites, thereby facilitating charge transportation between the electrocatalyst and electrolyte. This work provides insight into rational design and low-cost synthesis of nonprecious transition-metal chalcogenide-based electrocatalysts with high efficiency and excellent stability for HER.

Self-Assembled Coral-like Hierarchical Architecture Constructed by NiSe2 Nanocrystals with Comparable Hydrogen-Evolution Performance of Precious Platinum Catalyst.

For the first time, self-assembled coral-like hierarchical architecture constructed by NiSe2 nanocrystals has been synthesized via a facile one-pot DMF-solvothermal method. Compared with hydrothermally synthesized NiSe2 (H-NiSe2), the DMF-solvothermally synthesized nanocrystalline NiSe2 (DNC-NiSe2) exhibits superior performance of hydrogen evolution reaction (HER): it has a very low onset overpotential of ∼136 mV (vs RHE), a very high cathode current density of 40 mA/cm2 at ∼200 mV (vs RHE), and an excellent long-term stability; most importantly, it delivers an ultrasmall Tafel slope of 29.4 mV dec-1, which is the lowest ever reported for NiSe2-based catalysts, and even lower than that of precious platinum (Pt) catalyst (30.8 mV dec-1). The superior HER performance of DNC-NiSe2 is attributed to the unique self-assembled coral-like network, which is a benefit to form abundant active sites and facilitates the charge transportation due to the inherent high conductivity of NiSe2 nanocrystals. The DNC-NiSe2 is promising to be a viable alternative to precious metal catalysts for hydrogen evolution.

Flexible, transparent and high-power triboelectric generator with asymmetric graphene/ITO electrodes.

The reported flexible and transparent triboelectric generator (FTTG) can only output ultralow power density (∼2 µW cm(-2)), which has seriously hindered its further development and application. The low power density of FTTG is mainly limited by the transparent material and the electrode structure. Herein, for the first time, a FTTG with a superior power density of 60.7 µW cm(-2) has been fabricated by designing asymmetric electrodes where graphene and indium tin oxide (ITO) act as top and bottom electrodes respectively. Moreover, the performance of FTTG with graphene/ITO (G/I) asymmetric electrodes (GI-FTTG) almost remains unchanged even after 700 cycles, indicating excellent mechanical stability. The excellent performance of GI-FTTG can be attributed to the suitable materials and unique asymmetric electrode structure: the extraordinary flexibility of the graphene top electrode ensures the GI-FTTG excellent mechanical robustness and stability even after longer cycles, and the bottom electrode with very low sheet resistance guarantees lower internal resistance and higher production rate of induction charges to obtain higher output power density. It shows that light-emitting diodes (LED) can be easily powered by GI-FTTG, which demonstrates that the GI-FTTG is very promising for harvesting electrical energy from human activities by using flexible and transparent devices.

Flexible terahertz modulator based on coplanar-gate graphene field-effect transistor structure.

The terahertz (THz) modulators, as an essential component of the THz system, have been developed by many efforts until now. However, the development of flexible THz modulators is hindered due to the lack of flexible THz modulating materials. Herein, for the first time to the best of our knowledge, we demonstrated the feasibility of flexible THz modulators based on the coplanar-gate field-effect transistor (FET) structure of ion-gel/graphene/polyethylene terephthalate. The THz transmittance through this THz graphene modulator can be well controlled with a modulation depth up to 22% by tuning the carrier concentration of graphene via electrical gating. Furthermore, because of the integration of high flexibilities of graphene, ion-gel, and polyethylene terephthalate (PET), the proposed THz graphene modulator shows superior flexible performance, where the modulation properties can be maintained almost unchanged, not only under bending deformations, but also before and after bending 1000 times. In addition, due to the unique structure of ion-gel/graphene/PET, the flexible THz graphene modulator has a low insertion loss (1.2 dB). Therefore, this Letter is expected to be beneficial for the potential applications, ranging from the traditional compact THz system to a new flexible THz technology.

Observation of tunable electrical bandgap in large-area twisted bilayer graphene synthesized by chemical vapor deposition.

Although there are already many efforts to investigate the electronic structures of twisted bilayer graphene, a definitive conclusion has not yet been reached. In particular, it is still a controversial issue whether a tunable electrical (or transport) bandgap exists in twisted bilayer graphene film until now. Herein, for the first time, it has been demonstrated that a tunable electrical bandgap can be opened in the twisted bilayer graphene by the combination effect of twist and vertical electrical fields. In addition, we have also developed a facile chemical vapor deposition method to synthesize large-area twisted bilayer graphene by introducing decaborane as the cocatalyst for decomposing methane molecules. The growth mechanism is demonstrated to be a defined-seeding and self-limiting process. This work is expected to be beneficial to the fundamental understanding of both the growth mechanism for bilayer graphene on Cu foil and more significantly, the electronic structures of twisted bilayer graphene.

Control of anatase TiO2 nanocrystals with a series of high-energy crystal facets via a fuorine-free strategy.

The shape of it: A series of anatase TiO(2) nanocrystals with exposed high-energy {001} facets or high-index {103}, {102} facets and/or low-energy {101} facets were successfully synthesized via a fluorine-free route, and crystal-facet-dependent photodegradation activities were found to follow the sequence of {001}>{102}≈{103}>{101} (see picture; the scale bars are 200 nm).