Structure and inhibition mechanism of the human citrate transporter NaCT.

Citrate is best known as an intermediate in the tricarboxylic acid cycle of the cell. In addition to this essential role in energy metabolism, the tricarboxylate anion also acts as both a precursor and a regulator of fatty acid synthesis1-3. Thus, the rate of fatty acid synthesis correlates directly with the cytosolic concentration of citrate4,5. Liver cells import citrate through the sodium-dependent citrate transporter NaCT (encoded by SLC13A5) and, as a consequence, this protein is a potential target for anti-obesity drugs. Here, to understand the structural basis of its inhibition mechanism, we determined cryo-electron microscopy structures of human NaCT in complexes with citrate or a small-molecule inhibitor. These structures reveal how the inhibitor-which binds to the same site as citrate-arrests the transport cycle of NaCT. The NaCT-inhibitor structure also explains why the compound selectively inhibits NaCT over two homologous human dicarboxylate transporters, and suggests ways to further improve the affinity and selectivity. Finally, the NaCT structures provide a framework for understanding how various mutations abolish the transport activity of NaCT in the brain and thereby cause epilepsy associated with mutations in SLC13A5 in newborns (which is known as SLC13A5-epilepsy)6-8.

Preferred Orientation and Phase Distribution of Quasi-2D Perovskite for Bifunctional Light-Emitting Photodetectors.

In traditional optical wireless communication (OWC) systems, the simultaneous use of multiple sets of light-emitting diodes (LEDs) and photodetectors (PDs) increases the system complexity and instability. Here we report bifunctional light-emitting photodetectors (LEPDs) fabricated with quasi-2D perovskite (F-PEA)2Cs4Pb5I11Br5 as light-emitting/detecting layers for efficient, miniaturized, and intelligent bidirectional OWC. By simply changing the solvent composition of the precursor solution and using antisolvent engineering, we manipulated the crystal orientation and phase distribution of (F-PEA)2Cs4Pb5I11Br5, realizing high irradiance (4.36 µW cm-2) and a -3 dB refresh rate (0.21 MHz) of electroluminescence in LED mode as well as low noise (below 1 pA Hz-1/2) and high responsivity (0.1 A W-1) in PD mode. The rapid and accurate OWC process was demonstrated through interaction of LEPDs. We also demonstrated the high-fidelity compression and digitization of high-resolution (256 × 256 pixels) color images using the four-step phase shift method to realize intelligent encrypted image OWC.

Water-Stable and Sensitive X-ray Detectors by Supramolecular Interaction-Enhanced Polyoxometalates.

Polyoxometalates (POMs) have shown prominence in the field of semiconductive materials in recent years. However, electronic applications based on these emerging materials are still in their early stages. Here, a sensitive and water-stable F-PEA-ZnW12 X-ray detector has been designed and constructed for hard X-ray detection and imaging. Supramolecular interactions of H···O bonding, electrostatic, and anion-π interactions not only enable FPEA-ZnW12 excellent water stability but also shorten the distance between [ZnW12O40]6- clusters, which reduces ion migration and dark current simultaneously, resulting in the conductivity of 3.2 × 10-11 S cm-1. Furthermore, the heteropoly blue formed on the surface of the O-FPEA-ZnW12 wafer device promotes the effective separation and extraction of X-ray-induced carriers, enhancing the sensitivity for X-ray detection. The R/O-FEPA-ZnW12 wafer device yields a high sensitivity of 3.1 × 104 µC Gyair-1 cm-2 with the lowest detectable dose rate of 69 nGyair s-1 under 120 kV hard X-ray irradiation. In addition, the O-FPEA-ZnW12 wafer detector exhibits the potential for X-ray detection in water with a sensitivity of 1.0 × 104 µC Gyair-1 cm-2. Moreover, the fabricated POM X-ray detector shows excellent X-ray imaging capability and long-term operational stability without any attenuation of 1 year exposure to air without any encapsulation.

Structural basis for inhibition of the drug efflux pump NorA from Staphylococcus aureus.

Membrane protein efflux pumps confer antibiotic resistance by extruding structurally distinct compounds and lowering their intracellular concentration. Yet, there are no clinically approved drugs to inhibit efflux pumps, which would potentiate the efficacy of existing antibiotics rendered ineffective by drug efflux. Here we identified synthetic antigen-binding fragments (Fabs) that inhibit the quinolone transporter NorA from methicillin-resistant Staphylococcus aureus (MRSA). Structures of two NorA-Fab complexes determined using cryo-electron microscopy reveal a Fab loop deeply inserted in the substrate-binding pocket of NorA. An arginine residue on this loop interacts with two neighboring aspartate and glutamate residues essential for NorA-mediated antibiotic resistance in MRSA. Peptide mimics of the Fab loop inhibit NorA with submicromolar potency and ablate MRSA growth in combination with the antibiotic norfloxacin. These findings establish a class of peptide inhibitors that block antibiotic efflux in MRSA by targeting indispensable residues in NorA without the need for membrane permeability.

Preliminary study on the enhanced bioremediation of PAH-contaminated soil in Beijing and assessment of remediation effects based on toxicity tests.

In this study, we focused on soil contaminated by polycyclic aromatic hydrocarbons (PAHs) at typical coking-polluted sites in Beijing, conducted research on enhanced PAH bioremediation and methods to evaluate remediation effects based on toxicity testing, and examined changes in pollutant concentrations during ozone preoxidation coupled with biodegradation in test soil samples. The toxicity of mixed PAHs in soil was directly evaluated using the Ames test, and the correlation between mixed PAH mutagenicity and benzo(a)pyrene (BaP) toxicity was investigated in an effort to establish a carcinogenic risk assessment model based on biological toxicity tests to evaluate remediation effects on PAH-contaminated soil. This study provides a theoretical and methodological foundation for evaluating the effect of bioremediation on PAH-contaminated soil at industrially contaminated sites. The results revealed that the removal rate of PAHs after 5 min of O3 preoxidation and 4 weeks of soil reaction with saponin surfactants and medium was 83.22%. The soil PAH extract obtained after remediation had a positive effect on the TA98 strain at a dose of 2000 µg·dish-1, and the carcinogenic risk based on the Ames toxicity test was 8.98 times greater than that calculated by conventional carcinogenic PAH toxicity parameters. The total carcinogenic risk of the remediated soil samples was approximately one order of magnitude less than that of the original soil samples.

Low Bandgap 2D Perovskite Single Crystal with Anomalous-large Charges/ions Collection Ratio for Ultra-sensitive and Stable X-ray Detectors.

The low-dimensional halide perovskites have attracted increasing attention due to their improved moisture stability, reduced defects, and suppressed ions migration in many optoelectronic devices such as solar cells, light-emitting diodes, X-ray detectors, and so on. However, they are still limited by their large band gap and short charge carriers' diffusion length. Here, we demonstrate that the introduction of metal ions into organic interlayers of two-dimensional (2D) perovskite by cross-linking the copper paddle-wheel cluster-based lead bromide ([Cu(O2 C-(CH2 )3 -NH3 )2 ]PbBr4 ) perovskite single crystals with coordination bonds can not only significantly reduce the perovskite band gap to 0.96 eV to boost the X-ray induced charge carriers, but can also selectively improve the charge carriers' transport along the out-of-plane direction and blocking the ions motion paths. The [Cu(O2 C-(CH2 )3 -NH3 )2 ]PbBr4 single-crystal device can reach a record charges/ions collection ratio of 1.69×1018 ±4.7 % µGyair -1 s, and exhibit a large sensitivity of 1.14×105 ±7% µC Gyair -1 cm-2 with the lowest detectable dose rate of 56 nGyair s-1 under 120 keV X-rays irradiation. In addition, [Cu(O2 C-(CH2 )3 -NH3 )2 ]PbBr4 single-crystal detector exposed to the air without any encapsulation shows excellent X-ray imaging capability with long-term operational stability without any attenuation of 120 days.

Six-Transmembrane Epithelial Antigen of Prostate 1 (STEAP1) Has a Single b Heme and Is Capable of Reducing Metal Ion Complexes and Oxygen.

STEAP1, six-transmembrane epithelial antigen of prostate member 1, is strongly expressed in several types of cancer cells, particularly in prostate cancer, and inhibition of its expression reduces the rate of tumor cell proliferation. However, the physiological function of STEAP1 remains unknown. Here for the first time, we purified a mammalian (rabbit) STEAP1 at a milligram level, permitting its high-quality biochemical and biophysical characterizations. We found that STEAP1 likely assembles as a homotrimer and forms a heterotrimer when co-expressed with STEAP2. Each STEAP1 protomer binds one heme prosthetic group that is mainly low-spin with a pair of histidine axial ligands, with small portions of high-spin and P450-type heme. In its ferrous state, STEAP1 is capable of reducing transition metal ion complexes of Fe3+ and Cu2+. Ferrous STEAP1 also reacts readily with O2 through an outer sphere redox mechanism. Kinetics with all three substrates are biphasic with ∼80 and ∼20% for the fast and slow phases, respectively, in line with its heme heterogeneity. STEAP1 retained a low level of bound FAD during purification, and the binding equilibrium constant, KD, was ∼30 µM. These results highlight STEAP as a novel metal reductase and superoxide synthase and establish a solid basis for further research into understanding how STEAP1 activities may affect cancer progression.

Arising 2D Perovskites for Ionizing Radiation Detection.

2D perovskites have greatly improved moisture stability owing to the large organic cations embedded in the inorganic octahedral structure, which also suppresses the ions migration and reduces the dark current. The suppression of ions migration by 2D perovskites effectively suppresses excessive device noise and baseline drift and shows excellent potential in the direct X-ray detection field. In addition, 2D perovskites have gradually emerged with many unique properties, such as anisotropy, tunable bandgap, high photoluminescence quantum yield, and wide range exciton binding energy, which continuously promote the development of 2D perovskites in ionizing radiation detection. This review aims to systematically summarize the advances and progress of 2D halide perovskite semiconductor and scintillator ionizing radiation detectors, including reported alpha (α) particle, beta (ß) particle, neutron, X-ray, and gamma (γ) ray detection. The unique structural features of 2D perovskites and their advantages in X-ray detection are discussed. Development directions are also proposed to overcome the limitations of 2D halide perovskite radiation detectors.

Robust Organogel Scintillator for Self-healing and Ultra-flexible X-ray Imaging.

Metal halide scintillators serve as promising candidates for X-ray detection due to their high attenuation coefficients, high light yields, and low-cost solution-processable characteristics. However, the issues of humidity/thermal quenching and mechanical fragility, remain obstacles to the broad and diversified development of metal halide scintillators. Here, this work reports a lead-free, water-stable, stretchable, and self-healing (ethylenebis-triphenylphosphonium manganese (II) bromide (C38H34P2)MnBr4 organogel scintillator that meets X-ray imaging in complex scenarios. The robust organogel scintillator can be stretched with elongation up to 1300% while maintaining the scintillation properties. Activated by the dynamic hydrogen bonds and coordination bonds design, the organogel scintillator exhibits excellent self-healing properties at room temperature to alleviate the vignetting problem of the rigid scintillator films, the X-ray imaging resolution can reach 16.7 lp mm-1. The organogel scintillator can also realize flexible and self-healing X-ray imaging in water, providing a design path for portable devices in harsh conditions.

Bi Nanospheres Embedded in N-Doped Carbon Nanowires Facilitate Ultrafast and Ultrastable Sodium Storage.

Sodium ion batteries (SIBs) are considered as the ideal candidates for the next generation of electrochemical energy storage devices. The major challenges of anode lie in poor cycling stability and the sluggish kinetics attributed to the inherent large Na+ size. In this work, Bi nanosphere encapsulated in N-doped carbon nanowires (Bi@N-C) is assembled by facile electrospinning and carbonization. N-doped carbon mitigates the structure stress/strain during alloying/dealloying, optimizes the ionic/electronic diffusion, and provides fast electron transfer and structural stability. Due to the excellent structure, Bi@N-C shows excellent Na storage performance in SIBs in terms of good cycling stability and rate capacity in half cells and full cells. The fundamental mechanism of the outstanding electrochemical performance of Bi@N-C has been demonstrated through synchrotron in-situ XRD, atomic force microscopy, ex-situ scanning electron microscopy (SEM) and density functional theory (DFT) calculation. Importantly, a deeper understanding of the underlying reasons of the performance improvement is elucidated, which is vital for providing the theoretical basis for application of SIBs.

Differential perovskite hemispherical photodetector for intelligent imaging and location tracking.

Advanced photodetectors with intelligent functions are expected to take an important role in future technology. However, completing complex detection tasks within a limited number of pixels is still challenging. Here, we report a differential perovskite hemispherical photodetector serving as a smart locator for intelligent imaging and location tracking. The high external quantum efficiency (~1000%) and low noise (10-13 A Hz-0.5) of perovskite hemispherical photodetector enable stable and large variations in signal response. Analysing the differential light response of only 8 pixels with the computer algorithm can realize the capability of colorful imaging and a computational spectral resolution of 4.7 nm in a low-cost and lensless device geometry. Through machine learning to mimic the differential current signal under different applied biases, one more dimensional detection information can be recorded, for dynamically tracking the running trajectory of an object in a three-dimensional space or two-dimensional plane with a color classification function.

Influence of comprehensive nursing cooperation on complications and quality of life in patients with video laryngoscope-guided orotracheal intubation in lateral decubitus position.

OBJECTIVE: To retrospectively analyze the influence of nursing cooperation on complications and quality of life (QoL) in patients with video laryngoscope-guided orotracheal intubation in a lateral decubitus position (LDP). METHODS: A total of 130 patients with orotracheal intubation under general anesthesia in LDP from January 2020 to December 2021 were included and grouped based on the nursing model they received, with 65 patients receiving routine nursing cooperation during operation being included in a control group (the Con), and 65 patients receiving comprehensive nursing cooperation on the basis of the Con being included in an observation group (the Obs). The effect of the two nursing intervention models on acute pressure ulcer degree, complications, doctor-patient satisfaction, duration and area of pressure injury, nursing costs, and QoL were compared. RESULTS: The incidence of intraoperative acute pressure injury differed significantly between the Obs (3.08%) and the Con (21.54%) (P<0.05). The Obs also showed lower incidences of complications such as pressure injury, limb swelling, limb numbness and muscle soreness than the Con did (P<0.05). The satisfaction of nurses, patients, anesthesiologists and surgeons in the Obs group were all 100.00%, which was higher than those in the Con (93.85%, 89.23%, 92.31% and 90.77%, respectively). Patients in the Obs had shorter duration of pressure injury, smaller pressure injury area and less nursing cost (P<0.05). After nursing, the scores of social/physical functioning, vitality, role-emotional/physical, mental health, and bodily pain were all better in the Obs than in the Con (P<0.05). CONCLUSIONS: The implementation of comprehensive nursing cooperation for patients with video laryngoscope-guided orotracheal intubation in LDP can reduce the incidence of complications, lower the degree of acute pressure injury, improve doctor-patient satisfaction, and enhance the QoL of patients.

Prominent Free Charges Tunneling Through Organic Interlayer of 2D Perovskites.

The diversity of organic cations greatly enriches the species of 2D perovskites; traditional 2D Ruddlesden-Popper (RP) and Dion-Jacobson (DJ) perovskites are synthesized by two different organic amines. Here, according to the difference in pKa values between conjugated acids of monoprotonated and biprotonated 4-(2-Aminoethyl)pyridine (4AEPy) ions, the 2D perovskites of RP (4AEPy)2 PbI4 and DJ (4AEPy)PbI4 from same organic amine is reported, which can realize reversible transformation under the treatment of HI and NH3 , respectively. The interaction of N-H···N hydrogen bond between adjacent organic molecules in (4AEPy)2 PbI4 leads to the bending conformation of ethylamine groups, which results in a 2.4 Å reduction in layer spacing compared to typical phenylethylamine lead iodine ((PEA)2 PbI4 ) 2D perovskite. Besides, the ethylamine groups of organic layers in (4AEPy)PbI4 are deeply inserted into octahedral cavities and directly participate in the construction of the conduction band minimum, which leads to a small exciton binding energy of 27.3 meV to generate free charges. The stronger coupling between the organic and inorganic layers and the minor exciton binding energy can promote the DJ phase to possess a more stable structure and better optoelectronic properties. Thus the (4AEPy)PbI4 device displays better light response and X-ray detection capability with a high sensitivity of 5627 µC Gyair -1 cm-2 and the lowest detectable dose rate of 20 nGyair s-1 .

Effects of Anticholinergic Drugs on Visual Acuity of Patients with Tracheal Intubation under General Anesthesia.

Background: General anesthesia (GA) is the core means of surgical intervention, mainly used for analgesia and anxiety relief. Therefore, it is necessary to understand the laboratory and clinical research results during induction of GA. Penehyclidine hydrochloride (PHCD) combined with atropine sulfate (Atr) has the potential to induce GA. However, the role of PHCD combined with Atr during tracheal intubation under GA remains unclear. Objective: The research is aimed at exploring the effects of preoperative PHCD or Atr on adverse reactions (ARs) in patients during tracheal intubation under general anesthesia (GA). Methods: This study retrospectively enrolled 473 patients who underwent surgery under GA induction and divided them into a research group (n = 234) and a control group (n = 239) according to preoperative use of PHCD (with or without). Both groups of patients were given Atr postoperatively and nursing intervention. Anesthesia-related indexes, ARs, and hemodynamics were observed and compared between the two groups. Results: There were no significant differences in anesthesia-related indexes and hemodynamics between the research group and the control group. The incidence of blurred vision and diplopia in the research group was higher than that in the control group. Conclusion: Preoperative PHCD combined with postoperative Atr should be avoided in clinical practice, or Atr rather than PHCD should be used preoperatively, so as to reduce the occurrence of blurred vision, diplopia, and other ARs.

Structural basis of ion - substrate coupling in the Na+-dependent dicarboxylate transporter VcINDY.

The Na+-dependent dicarboxylate transporter from Vibrio cholerae (VcINDY) is a prototype for the divalent anion sodium symporter (DASS) family. While the utilization of an electrochemical Na+ gradient to power substrate transport is well established for VcINDY, the structural basis of this coupling between sodium and substrate binding is not currently understood. Here, using a combination of cryo-EM structure determination, succinate binding and site-directed cysteine alkylation assays, we demonstrate that the VcINDY protein couples sodium- and substrate-binding via a previously unseen cooperative mechanism by conformational selection. In the absence of sodium, substrate binding is abolished, with the succinate binding regions exhibiting increased flexibility, including HPinb, TM10b and the substrate clamshell motifs. Upon sodium binding, these regions become structurally ordered and create a proper binding site for the substrate. Taken together, these results provide strong evidence that VcINDY's conformational selection mechanism is a result of the sodium-dependent formation of the substrate binding site.

Enhanced extraordinary terahertz transmission through coupling between silicon resonators.

By using Mie resonance coupling effects, low-loss silicon particles as receiving or transmitting antennas can strongly localize the electromagnetic field. Enhanced extraordinary optical transmission (EEOT) is generated by placing two such silicon particles symmetrically on both sides of subwavelength hole arrays in the terahertz (THz) region. When the hole radius r is 17 times smaller than the resonance wavelength λ (r/λ = 0.06), the enhancement factors of the resonator-hole and the resonator-resonator coupling structures are 154- and 629-fold compared to that of the hole-only structure, respectively. The current distribution, magnetic field and Poynting vector are numerically simulated to reveal the mechanism of the proposed structure. Moreover, the Mie resonance coupling and the induced THz EEOT can be tuned in a wide frequency range. Our results provide a reference for the miniaturization of THz systems.

Spray-coated perovskite hemispherical photodetector featuring narrow-band and wide-angle imaging.

Sphere imagers featuring specific wavelength recognition and wide-angle imaging are required to meet the fast development of modern technology. However, it is still challenging to deposit high-quality photosensitive layers on sphere substrates from low-cost solution processes. Here we report spray-coated quasi-two-dimensional phenylethylammonium/formamidinium lead halide (PEA2FAn-1PbnX3n+1) perovskite hemispherical photodetectors. The crystallization speed is manipulated by perovskite compositions, and the film thickness can be controlled by spray-coating cycles and solution concentration from tens of nanometers to hundreds of micrometers with a fast velocity of 1.28 × 10-4 cm3 s-1. The lens-free hemispherical photodetectors allow light response at a wide incident angle of 180°. Simultaneously, the wavelength selective response from visible to the near-infrared range is achieved with full width at half maximums (FWHMs) of ~20 nm, comparable to single-crystal devices. Wide-angle and wavelength-selective imaging are also demonstrated, which can find potential applications in intelligent recognition and intraoperative navigated surgery.

Independently tunable all-dielectric synthetic multi-spectral metamaterials based on Mie resonance.

A single metamaterial (MM) is generally designed to operate in only one band, and the MMs with different dimensions of meta-atoms are required to be integrated to achieve multi-spectral responses simultaneously. In this study, an all-dielectric synthetic multi-spectral metamaterial (SMM) that can efficiently operate in the visible and terahertz (THz) ranges by incorporating nanoscale features into microscale unit cells is demonstrated and investigated numerically. The resonant frequency of the proposed SMM in both regimes can be tuned independently by changing the geometric parameters such as diameter, gap, width and height of unit cells functional in two different regions, whilst maintaining high reflectance efficiency. Results show that a variety of colors can be produced from red to purple in the visible range with maximal reflectance as high as 83% while the peak frequency of the SMM can be adjusted from 8.12 to 2.13 THz in the THz range with maximum reflectance up to 94%. The reflection characteristics of the SMM mainly originate from the electric dipole (ED) and magnetic dipole (MD) resonances via Mie scattering in both regions. The strategy of this research offers the possibility of applications in bio/chemical sensing, multi-spectral imaging, filtering, detection, modulation and so on.

The ups and downs of elevator-type di-/tricarboxylate membrane transporters.

The divalent anion sodium symporter (DASS) family contains both sodium-driven anion cotransporters and anion/anion exchangers. The family belongs to a broader ion transporter superfamily (ITS), which comprises 24 families of transporters, including those of AbgT antibiotic efflux transporters. The human proteins in the DASS family play major physiological roles and are drug targets. We recently determined multiple structures of the human sodium-dependent citrate transporter (NaCT) and the succinate/dicarboxylate transporter from Lactobacillus acidophilus (LaINDY). Structures of both proteins show high degrees of structural similarity to the previously determined VcINDY fold. Conservation between these DASS protein structures and those from the AbgT family indicates that the VcINDY fold represents the overall protein structure for the entire ITS. The new structures of NaCT and LaINDY are captured in the inward- or outward-facing conformations, respectively. The domain arrangements in these structures agree with a rigid body elevator-type transport mechanism for substrate translocation across the membrane. Two separate NaCT structures in complex with a substrate or an inhibitor allowed us to explain the inhibition mechanism and propose a detailed classification scheme for grouping disease-causing mutations in the human protein. Structural understanding of multiple kinetic states of DASS proteins is a first step toward the detailed characterization of their entire transport cycle.

Fine-control-valve of halide perovskite single crystal quality for high performance X-ray detection.

Halide perovskite single crystals (HPSCs) provide a unique platform to study the optoelectronic properties of such emerging semiconductor materials, while the temperature induced crystal growth method often has an increased solute integration speed and/or unavoidable solute consumption, resulting in a soaring or slumping crystal growth rate of HPSCs. Here, we developed a universal and facile solvent-volatilization-limited-growth (SVG) strategy to finely control the crystal growth rate by the fine-control-valve for high quality crystal grown through solution processes. The grown HPSCs by SVG method exhibited a record low trap density of 2.8 × 108 cm-3 and a high charge carrier mobility-lifetime product (µτ product) of 0.021 cm2/V, indicating the excellent crystal quality. The crystal surface defects were further passivated by oxygen suppliers as Lewis base, which led to a reduction of surface leakage current by two times when using for low dose rate X-ray detection. Such HPSC X-ray detector displayed a high sensitivity of 1274 µC/(Gyair cm2) with a lowest detectable dose rate of 0.56 µGyair/s under 120 keV hard X-ray. Further applications including alloy composition analysis and metal flaw detection by HPSC detectors were also demonstrated, which not only shows the bright future for product quality inspection and non-destructive materials analysis, but also paves the way for growing high quality single crystals and fabricating polycrystalline films.