Identification of hyperoxidized PRDX3 as a ferroptosis marker reveals ferroptotic damage in chronic liver diseases.

Ferroptosis, a regulated cell death pathway driven by accumulation of phospholipid peroxides, has been challenging to identify in physiological conditions owing to the lack of a specific marker. Here, we identify hyperoxidized peroxiredoxin 3 (PRDX3) as a marker for ferroptosis both in vitro and in vivo. During ferroptosis, mitochondrial lipid peroxides trigger PRDX3 hyperoxidation, a posttranslational modification that converts a Cys thiol to sulfinic or sulfonic acid. Once hyperoxidized, PRDX3 translocates from mitochondria to plasma membranes, where it inhibits cystine uptake, thereby causing ferroptosis. Applying hyperoxidized PRDX3 as a marker, we determined that ferroptosis is responsible for death of hepatocytes in mouse models of both alcoholic and nonalcoholic fatty liver diseases, the most prevalent chronic liver disorders. Our study highlights the importance of ferroptosis in pathophysiological conditions and opens the possibility to treat these liver diseases with drugs that inhibit ferroptosis.

A cholesterol-binding bacterial toxin provides a strategy for identifying a specific Scap inhibitor that blocks lipid synthesis in animal cells.

Lipid synthesis is regulated by the actions of Scap, a polytopic membrane protein that binds cholesterol in membranes of the endoplasmic reticulum (ER). When ER cholesterol levels are low, Scap activates SREBPs, transcription factors that upregulate genes for synthesis of cholesterol, fatty acids, and triglycerides. When ER cholesterol levels rise, the sterol binds to Scap, triggering conformational changes that prevent activation of SREBPs and halting synthesis of lipids. To achieve a molecular understanding of how cholesterol regulates the Scap/SREBP machine and to identify therapeutics for dysregulated lipid metabolism, cholesterol-mimetic compounds that specifically bind and inhibit Scap are needed. To accomplish this goal, we focused on Anthrolysin O (ALO), a pore-forming bacterial toxin that binds cholesterol with a specificity and sensitivity that is uncannily similar to Scap. We reasoned that a small molecule that would bind and inhibit ALO might also inhibit Scap. High-throughput screening of a ~300,000-compound library for ALO-binding unearthed one molecule, termed UT-59, which binds to Scap's cholesterol-binding site. Upon binding, UT-59 triggers the same conformation changes in Scap as those induced by cholesterol and blocks activation of SREBPs and lipogenesis in cultured cells. UT-59 also inhibits SREBP activation in the mouse liver. Unlike five previously reported inhibitors of SREBP activation, UT-59 is the only one that acts specifically by binding to Scap's cholesterol-binding site. Our approach to identify specific Scap inhibitors such as UT-59 holds great promise in developing therapeutic leads for human diseases stemming from elevated SREBP activation, such as fatty liver and certain cancers.

pH-responsive bentonite nanoclay carriers control the release of benzothiazolinone to restrain bacterial wilt disease.

Ralstonia solanacearum (R. solanacearum) is one of the most devastating pathogens in terms of losses in agricultural production. Bentonite (Bent) is a promising synergistic agent used in development of effective and environmentally friendly pesticides against plant disease. However, the synergistic mechanism of Bent nanoclays with benzothiazolinone (BIT) against R. solanacearum is unknown. In this work, acid-functionalized porous Bent and cetyltrimethylammonium bromide (CTAB) were employed as the core nanoclays, and BIT was loaded into the clay to form BIT-loaded CT-Bent (BIT@CT-Bent) for the control of bacterial wilt disease. BIT@CT-Bent exhibited pH-responsive release behavior that fit the Fickian diffusion model, rapidly releasing BIT in an acidic environment (pH = 5.5). The antibacterial effect of BIT@CT-Bent was approximately 4 times greater than that of the commercial product BIT, and its biotoxicity was much lower than that of BIT under the same conditions. Interestingly, R. solanacearum attracted BIT@CT-Bent into the nanocomposites and induced cytoplasmic leakage and changes in membrane permeability, indicating an efficient and synergistic bactericidal effect that rapidly reduced bacterial density. In addition, BIT@CT-Bent significantly inhibited R. solanacearum biofilm formation and swimming activity, by suppressing the expression of phcA, solR and vsrC. Indeed, exogenous application of BIT@CT-Bent significantly suppressed the virulence of R. solanacearum on tobacco plants, with control effect of 75.48%, 72.08% and 66.08% at 9, 11 and 13 days after inoculation, respectively. This study highlights the potential of using BIT@CT-Bent as an effective, eco-friendly bactericide to control bacterial wilt diseases and for the development of sustainable crop protection strategies.

Cocrystallization-driven Formation of fcc-based Ag110 Nanocluster with Chinese Triple Luban Lock Shape.

Luban locks with mortise and tenon structure have structural diversity and architectural stability, and it is extremely challenging to synthesize Luban lock-like structures at the molecular level. In this work, we report the cocrystallization of two structurally related atom-precise fcc silver nanoclusters Ag110 (SPhF)48 (PPh3 )12 (Ag110 ) and Ag14 (µ6 -S)(SPhF)12 (PPh3 )8 (Ag14 ). It is worth noting that the Ag110 cluster is the first compound to simulate the complex Luban lock structure at the molecular level. Meanwhile, Ag110 is the largest known fcc-based silver nanocluster, so far, there is no precedent for fcc silver nanocluster with more than 100 silver atoms. DFT calculations show that Ag110 is a 58-electron superatom with an electronically closed shell1S2 1P6 1D10 2S2 1F14 2P6 1G18 . Ag110 ⋅Ag14 can rapidly catalyze the reduction of 4-nitrophenol within 4 minutes. In addition, Ag110 presents clear structural evidence to reveal the critical size and mechanism of the transformation of metal core from fcc stacking to quasi-spherical superatom. This research work provides an important structural model for studying the nucleation mechanism and structural assembly of silver nanoclusters.

Improved topography measurement with a high dynamic range using phase difference sensing technology.

Phase difference sensing technology (PDST) is employed for topography measurement, and two interference structures are proposed to achieve upper-limit adjustment and high resolution in the measurement range: a dual-wavelength system with a single Fabry-Perot (FP) cavity and a single-wavelength system with dual FP cavities. The phase difference between the two interference signals is determined by an elliptic fitting algorithm (EFA), and this change in phase difference is utilized to characterize the step height. Experimental results indicate that the measurement upper-limit can be adjusted to either 410 µm, 187 µm, or 108 µm by varying the wavelength difference in the dual-wavelength system, which gives a measurement error of 2.96%. In contrast, while offering a measurement resolution of 3.47 nm, the single-wavelength system exhibits a measurement error of 5.38%. The proposed method is capable of satisfying the measurement requirements during micro-electromechanical system (MEMS) processing with proficiency.

Selective Photochromic Response to Low-Dose X-ray Radiation Detection in One-Dimensional Cadmium-Viologen Complexes.

Photochromic viologen-based materials have emerged as one of the most promising candidates for the development of X-ray light detection applications, including medical diagnosis and treatment, environmental radiation inspection, and industrial crack detection. However, the design and construction of low-dose X-ray-sensitive complexes remains an immense challenge, especially for the in-depth dissection of their response mechanisms. Herein, by using N,N'-4,4'-bipyridiniodipropionate (CV) as functional sensitive structural units and cadmium as heavy atoms, two cadmium-viologen complexes with one-dimensional chained structures, namely, [Cd2Cl4(CV)(H2O)2]n (1) and [CdBr2(CV)]n (2), have been constructed, which exhibit a remarkable and selective photochromic response to low-dose X-ray radiation detection. Compound 1 is visually sensitive to both X-ray and UV light due to the more accessible photoinduced electron transfer (ET) pathways, while compound 2 only shows a slight color-changing process in response to UV light, in conformity with UV-vis absorbance analyses and kinetic studies. Surprisingly, compound 2 has longer ET pathways than 1, but not in response to high-energy X-ray light, seeming to contradict the previous phenomena. On further analysis, the key point in achieving X-ray-sensitive behavior should be a good balance among the electron donor-acceptor distance, intermolecular interaction, and X-ray absorbing capacity, as verified by density functional theory (DFT) and X-ray absorption strength calculations, X-ray photoelectron spectra, electron paramagnetic resonance measurements, and independent gradient model analysis. In particular, compound 1 is unprecedentedly sensitive to soft X-ray radiation, accompanied by an X-ray detection limit of as low as 2.91 Gy. These findings push forward the further development of low-dose X-ray sensing materials.

Identification of a degradation signal at the carboxy terminus of SREBP2: A new role for this domain in cholesterol homeostasis.

Lipid homeostasis in animal cells is maintained by sterol regulatory element-binding proteins (SREBPs), membrane-bound transcription factors whose proteolytic activation requires the cholesterol-sensing membrane protein Scap. In endoplasmic reticulum (ER) membranes, the carboxyl-terminal domain (CTD) of SREBPs binds to the CTD of Scap. When cholesterol levels are low, Scap escorts SREBPs from the ER to the Golgi, where the actions of two proteases release the amino-terminal domains of SREBPs that travel to the nucleus to up-regulate expression of lipogenic genes. The CTD of SREBP remains bound to Scap but must be eliminated so that Scap can be recycled to bind and transport additional SREBPs. Here, we provide insights into how this occurs by performing a detailed molecular dissection of the CTD of SREBP2, one of three SREBP isoforms expressed in mammals. We identify a degradation signal comprised of seven noncontiguous amino acids encoded in exon 19 that mediates SREBP2's proteasomal degradation in the absence of Scap. When bound to the CTD of Scap, this signal is masked and SREBP2 is stabilized. Binding to Scap requires an arginine residue in exon 18 of SREBP2. After SREBP2 is cleaved in Golgi, its CTD remains bound to Scap and returns to the ER with Scap where it is eliminated by proteasomal degradation. The Scap-binding motif, but not the degradation signal, is conserved in SREBP1. SREBP1's stability is determined by a degradation signal in a different region of its CTD. These findings highlight a previously unknown role for the CTD of SREBPs in regulating SREBP activity.

Phase-shifted demodulation technique with additional modulation based on a 3 × 3 coupler and EFA for the interrogation of fiber-optic interferometric sensors.

A phase-shifted demodulation technique with a 3×3 coupler and ellipse fitting algorithm (EFA) for the interrogation of interferometric sensors is proposed. To reduce the error of the EFA as to measure small phase signals, additional phase modulation is introduced. The additional modulation provides a walk of the operating point along the Lissajous ellipse large enough to permit calculation of the ellipse parameters at every moment. Experimental result shows that this technique demonstrates high accuracy and stability for measuring small phase signals. The setting of this technology expands the application of the EFA in fiber-optic phase demodulation technology.

Large-range phase-difference sensing technology for low-frequency strain interrogation.

Phase-difference sensing technology (PDST) has been applied to strain measurement, but its completeness is destroyed by the phase-difference measurement range. A scheme that can realize the completeness of the PDST for low-frequency strain interrogation is proposed. It is built on dual-interferometers and the elliptic-fitting algorithm. To break the measurement range limitation (0, π), a phase compensation setting is applied. The experimental results demonstrate that the method can obtain low-frequency strain signals, and the low-frequency signal whose phase amplitude is greater than π is recovered. The scheme is an efficient and complete method for measuring the strain of low-frequency optical fiber length, which could be applied to low-frequency seismic wave monitoring and rock deformation detection.

A One-Dimensional Broadband Emissive Hybrid Lead Iodide with Face-Sharing PbI6 Octahedral Chains.

One-dimensional (1D) organic-inorganic hybrid lead halides with unique core-shell quantum wire structures and splendid photoluminescence properties have been considered one of the most promising high-efficiency broadband emitters. However, studies on the broadband emissions in 1D purely face-shared lead iodide hybrids are still rare so far. Herein, we report on a new 1D lead iodide hybrid, (2cepyH)PbI3 (2cepy = 1-(2-chloroethyl)pyrrolidine), characterized with face-sharing PbI6 octahedral chains. Upon UV photoexcitation, this material shows broadband yellow emissions originating from the self-trapped excitons associated with distorted Pb-I lattices on account of the strong exciton-phonon coupling, as proved by variable-temperature emission spectra. Moreover, experimental and calculated results reveal that (2cepyH)PbI3 is an indirect bandgap semiconductor, the band structures of which are governed by inorganic parts. Our work represents the first broadband emitter based on a 1D face-shared lead iodide hybrid and opens a new way to obtain the novel broadband emission materials.

Discovery of a novel plant-derived agent against Ralstonia solanacearum by targeting the bacterial division protein FtsZ.

Ralstonia solanacearum (R. solanacearum) is one of the most devastating bacterial pathogens and leads to serious economic losses in crops worldwide. In this study, the antibacterial activities of novel plant-derived coumarins against R. solanacearum and their underlying mechanisms were initially investigated. The bioactivity assay results showed that certain coumarins had significant in vitro inhibitory effects against R. solanacearum. Notably, 6-methylcoumarin showed the best in vitro antibacterial activity with 76.79%. Interestingly, 6-methylcoumarin was found to cause cell elongation, disrupt cell division, and suppress the expression of the bacterial division protein coding genes ftsZ. Compared with the control treatment, the ∆ftsZ mutant inhibited bacterial growth and caused the bacteria to be more sensitive to 6-methylcoumarin. The application of 6-methylcoumarin effectively suppressed the development of tobacco bacterial wilt in pot and field experiments, and significantly reduced the bacterial population in tobacco stems. The control efficiency of 6-methylcoumarin treatment was 35.76%, 40.51%, 38.99% at 10, 11, and 12 weeks after tobacco transplantation in field condition. All of these results demonstrate that 6-methylcoumarin has potential as an eco-friendly and target specificity agent for controlling tobacco bacterial wilt.

Plant secondary metabolite, daphnetin reduces extracellular polysaccharides production and virulence factors of Ralstonia solanacearum.

Plants deploy a variety of secondary metabolites to fend off pathogen attack. Certain plants could accumulate coumarins in response to infection of bacteria, fungi, virus and oomycetes. Although coumarins are generally considered toxic to microbes, the exact mechanisms are often unknown. Here, we showed that a plant secondary metabolite daphnetin functions primarily by inhibiting Ralstonia solanacearum extracellular polysaccharides (EPS) production and biofilm formation in vitro, through suppressing genes expression of xpsR, epsE, epsB and lexM. Indeed, daphnetin significantly impaired virulence of R. solanacearum on tobacco plants. Transcriptional analysis suggested that daphnetin suppresses EPS synthesis cluster genes expression through transcriptional regulator XpsR. And daphnetin alter mainly virulence factors genes involved in type III secretion system, and type IV secretion system. R. solanacearum lacking EPS synthesis genes (epsB and epsC) that do not produce EPS, showed less virulence on tobacco plants. Molecular docking results indicated that the critical residues of domain in the binding pocket of the EpsB protein interact with daphnetin via conventional hydrogen bonding and hydrophobic interactions. Collectively, we found that daphnetin has potential as a novel virulence inhibitor of R. solanacearum, directly regulates EPS synthesis genes expression.

Axial strain applied in-fiber Mach-Zehnder interferometer for acceleration measurement.

We present an axial strain applied in-fiber Mach-Zehnder interferometer (MZI) for acceleration measurement. A thin core fiber is sandwiched between two single-mode fibers with core offset to form the MZI. A controlled high fringe visibility in the transmission spectrum is obtained by applying an axial strain, leading to a large slope at the quadrature point. The MZI is then clamped to work as an accelerometer. Experimental results show that the resolution achieves 86 ng/√Hz (g is gravity of 9.8 m/s2), the dynamic range reaches as large as 104.1 dB and the linearity of acceleration response is as high as 99.994%. Moreover, the resonance frequency can be tailored by the clamped fiber length and applied axial strain. The proposed sensor is attractive for practical applications due to low temperature crosstalk, compact size and high sensitivity.

Tri(pyridinyl)pyridine Viologen-Based Kagome Dual Coordination Polymer with Selective Chromic Response to Soft X-ray and Volatile Organic Amines.

The development of new responsive smart materials has been highly desirable in the recent decade due to growing demand in our daily life, and extended viologen-based coordination polymers are regarded as proper and promising candidates for stimuli-responsive study. A tri(pyridinyl)pyridine viologen-based Kagome dual (kgd) topological coordination polymer, [Mn3Cl4(tpptb)2]·Cl2·(H2O)2, (tpptb = N,N',N″-tri(3-carboxybenzyl)-2,4,6-tri(pyridinium-4-yl)pyridine; 1) has been solvothermally synthesized, which can selectively respond to soft X-ray Al-Kα (λ = 8.357 Å) irradiation but not to UV light and hard X-rays of λ < 1.5418 Å at room temperature. Appealingly, 1 is very sensitive and convenient for the visual detection of various volatile amine vapors, especially ethylamine vapors at a low concentration of 100 ppm, and the vapochromic sample can be recovered after exposure in the air at room temperature. The sequence of amines in vapochromism could be rationalized by combined consideration of vapor pressure, the molecular size, and electron-donor ability of various amine molecules as well as the void spaces of 1. In addition, 1 exhibits an obvious hydrochromic transformation upon heating in the air and an anhydrous atmosphere. Combined XPS and EPR confirmed that these physical and chemical stimuli can cause electron transfer from electron-rich groups to quaternary nitrogen atoms of the ligand to generate charge-separated radicals, leading to soft X-ray-induced photochromic and selective vapochromic behavior of 1. Such behavior indicates that it will become a convenient, recyclable, and practical multifunctional material for chemical and environmental sensing. These results provide an effective avenue for the rational design and synthesis of multifunctional chromic materials for potential use in sensing devices.

A single amino acid substitution in the FAD-binding domain causes the inactivation of Propionibacterium Acnes isomerase.

We previously demonstrated the efficient production of trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) in Lactococcus lactis by ectopically expressing a Propionibacterium acnes isomerase (pai) gene and also mentioned that a recombinant strain was unable to accumulate t10c12-CLA product, despite the normal transcription. Here, the molecular analysis indicated that this mutated strain harbors a pai gene with a single-nucleotide mutation converting GC50A to GTA, leading to a corresponding change of Alanine residue into Valine. The expression of the reverse mutation resulted in the recovery for enzyme activity. Site-directed mutagenesis indicated that the codon usage of Val17 was not responsible for the enzyme inactivation in the Ala17Val mutation. Western blot analysis revealed that the recombinant PAI protein was not detectable in the His tag-marked Ala17Val mutant. It is, therefore, reasonable to assume that Ala17 residue is critical for PAI functionality.Abbreviations: pai: propionibacterium acnes isomerase; CLA: conjugated linoleic acid; t10c12-CLA: trans 10, cis 12-CLA; LA: linoleic acid (18:2n-6); FAD: flavin adenine dinucleotide.

Miniaturized Fabry-Perot probe utilizing PMPCF for high temperature measurement.

We propose a miniaturized optical fiber Fabry-Perot probe for high temperature measurement (up to 1000°C). It is simply fabricated by fusion splicing a short section of polarization-maintaining photonic crystal fiber (PMPCF) with a single-mode fiber (SMF). The interface between the core of the SMF and air holes of the PMPCF, and the end face of the PMPCF work as the mirrors. The pure silica core of the PMPCF is employed as the sensing element. Experimental results show that the probe has a high thermal stability and the temperature sensitivity reaches up to 15.34 pm/°C, which is not affected by the length of the PMPCF. The linearity of temperature response is as high as 99.83%. The proposed sensor has promising prospects in practical applications due to simple fabrication process, low cost, compact size, and excellent repeatability.

Thin fiber-based Mach-Zehnder interferometric sensor for measurement of liquid level, refractive index, temperature, and axial strain.

An all-fiber Mach-Zehnder interferometric sensor capable of measuring liquid level, refractive index (RI), temperature, and axial strain is proposed and experimentally demonstrated. The proposed sensor is based on a fiber ball-thin fiber (TF)-core-offset structure sandwiched between two standard single-mode fibers. The variations of ambient liquid level, RI, temperature, and axial strain cause the change of phase difference between the cladding modes and the core mode, which leads to the shift of interference spectrum. The wavelength shifts of three resonant dips in the transmission spectrum are used to investigate the sensing characteristics of the sensor. Experimental results show that the sensor with TF length of 20 mm exhibits high RI and liquid-level sensitivities of $ - {131.7092}\;{\rm nm/RIU}$-131.7092nm/RIU and $ - {120.7}\;{\rm pm/mm}$-120.7pm/mm at a wavelength of 1589.5 nm. Meanwhile, the sensor is insensitive to temperature and axial strain, and the maximum sensitivities are 0.0390 nm/°C and $ - {4}.{84}\; \times \;{{10}^{ - 4}}\;{\rm nm}/\unicode{x00B5} \varepsilon $-4.84×10-4nm/µÎµ, respectively. In addition, the sensor shows superiority in measuring multiple parameters simultaneously.

X-ray and UV Dual Photochromism, Thermochromism, Electrochromism, and Amine-Selective Chemochromism in an Anderson-like Zn7 Cluster-Based 7-Fold Interpenetrated Framework.

Smart materials are highly desirable over the recent decade due to the growing demand of complicated nature. Stable stimuli-responsive smart materials exhibit widespread potential for applications in smart windows, sensors, separators, chemical valves, and release platforms but are rare. Despite being good candidates, viologen-based multifunctional smart materials are still a challenging task for chemists. To obtain such materials, the judicious strategy is to introduce polynuclear metal-carboxylate clusters as electron donors into a stable framework to increase chromic sensitivity. Toward this endeavor, we have synthesized a novel viologen-based polymer with a unique Anderson-like metal-carboxylate cluster, [Zn7(bpybc)3(o-BDC)6]·2NO3·6H2O (bpybc = 1,1'-bis(4-carboxyphenyl)-4,4'-bipyridinium, o-BDC = o-benzenedicarboylic acid) (1), which is a particular 7-fold interpenetrated framework with a 3D pcu network in which bpybc ligand as the linker and Zn7O30C12 as the second building unit (Zn7 SBU) were used as 6-connected nodes. More importantly, it shows excellent chromic behavior in response to multiple external stimuli especially soft X-ray and UV dual light, temperature, electricity, and organic amines, which stand out in the viologen-based polymers. Interestingly, the coloration process of 1 from "core" to "edge" is observed upon heating at the appropriate temperature, which has not yet been found in other reported thermochromic materials. Of particular interest for 1 is the couple of quaternary stimuli-sensitive abilities because it simultaneously meets the following conditions: (i) the capability of withstanding high light, higher temperature, extreme pH, and other harsh conditions; and (ii) the high sensitivity to external stimuli keeping away from photodegradation, thermal relaxation, side reactions, and so on. To be noted, 1 has high thermal stability and chemical stability, which are excellent advantages as smart materials. To further develop possible practical utilization, 1 has been doped into the polymer matrixes to construct a hybrid film, which not only keeps the response to external stimuli but also significantly improves the repeatability of the photochromic process, indicating that a new smart device with multi-stimuli-responsive functions will emerge successively in the future.

High temperature Vernier probe utilizing photonic crystal fiber-based Fabry-Perot interferometers.

This study proposes a highly sensitive and stable optical fiber probe based on Vernier effect for high temperature measurement (up to 1000 °C), utilizing photonic crystal fiber (PCF)-based Fabry-Perot interferometers (FPIs). The cascaded FPIs are fabricated by fusion splicing a section of polarization maintaining PCF to a lead-in single-mode fiber, and then a section of temperature-insensitive hollow core PCF is spliced between the PMPCF and a multi-mode fiber. The shift of the spectral envelope is monitored to measure the temperature variation. Experimental results show that the sensitivities of three fabricated probes are as high as 173.43 pm/ °C, 230.53 pm/ °C and 535.16 pm/ °C when operating from room temperature to 1000 °C, which are consistent with theoretical results. The sensitivities are magnified about 13, 19 and 45 times compared with the single FPI. The linearity of the temperature response is as high as 99.73%. The proposed probe has great application prospects due to compactness, high sensitivity and low cost.

Real-time acceleration sensing with an arctan algorithm based on a modal interferometer.

This study proposes a fiber-optic accelerometer for low-frequency vibration signal detection. The phase velocities of the polarization eigenmodes are affected differently by signals, leading to a polarization rotation of the transmitted lights. The orthogonal square roots of the photovoltages are utilized for an arctan demodulation scheme. Experimental results show that it provides a flat response of 75.04 mrad/g, an average resolution of 13.44 µg/√Hz, and a dynamic range of 111.62 dB below 180 Hz. The environmental instability and sensor complexity are significantly reduced, so that the sensor can be further used in the warning of coal and gas outburst.