Search

The control of the self-assembly of lanthanide helical chain as well as the helical handedness have been investigated for the first time. Δ- and Λ-form lanthanide chain were obtained by introducing the thiazolidine ligand synthesized from L-/D- cysteine, respective, which share the same formula, [Ln2(L)3(H2O)5]∞·3H2O (Ln: Sm and Eu)(L: 2-(2-hydroxy-3,5-dinitrophenyl)thiazolidine-4-carboxylic acid). Crystallographic characterization, circular dichroism and luminescent properties were studied for these four novel lanthanide chain complexes.

N-Dealkylation of amines by metal oxo intermediates (M Created by potrace 1.16, written by Peter Selinger 2001-2019 O) is related to drug detoxification and DNA repair in biological systems. In this study, we report the first example of N-dealkylation of various alkylamines by a luminescent osmium(vi) nitrido complex induced by visible light., The visible light-induced N-dealkylation of various alkylamines by a luminescent osmium(vi) nitrido complex has been investigated. We provide definitive evidence that these reactions occur via an ET/PT mechanism.

Charophyte assemblages from the Cretaceous/Paleogene (K/Pg) boundary transition in the JZK-2 borehole of the Jiaolai Basin (eastern China) were studied. The charophyte flora includes Tolypella grambastii, Peckichara praecursoria, Microchara cristata, Microchara prolixa, Chara changzhouensis, Lamprothamnium ellipticum, Nodosochara (Turbochara) specialis, Lychnothamnus aff. vectensis, and Lychnothamnus lanpingensis n. comb. The discovery of the ostracod species Porpocypris sphaeroidalis Guan in the upper section of the JZK-2 borehole strongly indicates the arrival of the Paleocene. Three floras of the latest Cretaceous to the early Paleocene were compared among the Jiaolai, Pingyi, and Songliao basins. The Pingyi Basin is special because it is the only carbonate palaeolake that occurred throughout the K/Pg transition in China. It is characterized by the appearance of the Cretaceous brackish water element, Feistiella anluensis (Wang), and is dominated by the Paleocene species, Peckichara varians Grambast. The Songliao and Jiaolai floras grow in clastic lakes; the Jiaolai Basin is thought to correspond to an altitude lake, which was formed in the coastal mountains with high palaeoelevation (≥ 2.0 km), while the Songliao Basin is presumed to have been formed in a low elevation site according to previous studies. This difference in altitude explains why the Songliao Basin is more species-rich than the Jiaolai Basin.

Four carbonyl hydrido RuII complexes with different functionalized α,α'-diimine ligands have been synthesized and well characterized by IR, UV/vis, CV, ESI/MS, and 1H NMR spectra. One of the complexes was also characterized by X-ray crystallography. The luminescence of these complexes has been investigated at room temperature in CH2Cl2 solution and low temperature glassy media at 77 K. The emissions are originated from either ligand-centered π–π* transitions or metal center to ligand charge transfer (MLCT), which are highly dependent on the properties of the α-diimine ligands.

We here described a direct catalytic asymmetric functionalization of 2-methylindoles using organocatalysis. An efficient asymmetric allylic alkylation reaction with respect to 2-methyl-3-nitroindoles and racemic Morita–Baylis–Hillman carbonate has been achieved by using a chiral biscinchona alkaloid catalyst, which provided the functionalized indole derivatives in good yields and enantioselectivities.

We report the nucleation and two dimensional (2D) crystallization of the helical aromatic hydrocarbon pentahelicene ([5]H) on the semimetallic Bi(111) surface studied via low-temperature scanning tunneling microscopy. Individual homochiral dimers and heterochiral trimers appear on the substrate at a low coverage. With an increase in the coverage, a chiral phase transition takes place from the 2D conglomerate of [5]H dimers to the 2D racemate of [5]H trimers. The heterochiral [5]H trimers reveal a wavy arrangement due to the swing of 5[H] trimer rows after every second or third trimers. The swing mechanism of the trimer rows can be attributed to the steric repulsion between the adjacent trimers with same handedness.

Dual oxidases (DUOXs) produce hydrogen peroxide by transferring electrons from intracellular NADPH to extracellular oxygen. They are involved in many crucial biological processes and human diseases, especially in thyroid diseases. DUOXs are protein complexes co-assembled from the catalytic DUOX subunits and the auxiliary DUOXA subunits and their activities are regulated by intracellular calcium concentrations. Here, we report the cryo-EM structures of human DUOX1-DUOXA1 complex in both high-calcium and low-calcium states. These structures reveal the DUOX1 complex is a symmetric 2:2 hetero-tetramer stabilized by extensive inter-subunit interactions. Substrate NADPH and cofactor FAD are sandwiched between transmembrane domain and the cytosolic dehydrogenase domain of DUOX. In the presence of calcium ions, intracellular EF-hand modules might enhance the catalytic activity of DUOX by stabilizing the dehydrogenase domain in a conformation that allows electron transfer., Dual oxidases (DUOXs), assembled from the catalytic DUOX and the auxiliary DUOXA subunits, produce hydrogen peroxide by transferring electrons from intracellular NADPH to extracellular oxygen in a calcium-activated manner. Here authors report the cryo-EM structures of human DUOX1-DUOXA1 complex in both high-calcium and low-calcium states.

The first-row transition metal compounds, [MII(L1)2](ClO4)2 (M = Ni (1); Co (2)), have been prepared by treatment of a neutral tetradentate ligand (L1 = N2,N9-dibutyl-1,10-phenanthroline-2,9-dicarboxamide) with metal perchlorate salts in MeOH. Both compounds have been structurally characterized by X-ray crystallography and it was found that the coordination numbers are 6 and 7, respectively. The reaction of 6,6′-bis(2-tbutyl-tetrazol-5-yl)-2,2′-bipyridine (L2) with hydrated FeII(ClO4)2 afforded a 8-coordinate Fe(II) compound, [FeII(L2)2](ClO4)2 (3); however its reaction with hydrated CoII(ClO4)2 resulted in 6-coordinate [CoII(L2)2](ClO4)2. It is interesting to observe field-induced slow magnetic relaxation in the 7-coordinate Co(II) compound 2 and 8-coordinate Fe(II) compound 3, which further supports the validity of designing high coordination number compounds as single-molecule magnets. Direct current magnetic studies demonstrate that 2 has a very large positive D value (56.2 cm−1) and a small E value (0.66 cm−1), indicating easy plane magnetic anisotropy. Consistent with the larger D value, an effective spin-reversal barrier of Ueff = 100 K (71.4 cm−1) is obtained, which is the highest value reported for 7-coordinate Co(II) complexes with a pentagonal bipyramidal geometry. In contrast, 8-coordinate Fe(II) compound 3 exhibits uniaxial magnetic anisotropy.

Acute respiratory distress syndrome/acute lung injury (ARDS/ALI) is histologically characterized by extensive alveolar barrier disruption and excessive fibroproliferation responses. Protectin DX (PDX) displays anti‐inflammatory and potent inflammation pro‐resolving actions. We sought to investigate whether PDX attenuates LPS (lipopolysaccharide)‐induced lung injury via modulating epithelial cell injury repair, apoptosis and fibroblasts activation. In vivo, PDX was administered intraperitoneally (IP) with 200 ng/per mouse after intratracheal injection of LPS, which remarkedly stimulated proliferation of type II alveolar epithelial cells (AT II cells), reduced the apoptosis of AT II cells, which attenuated lung injury induced by LPS. Moreover, primary type II alveolar cells were isolated and cultured to assess the effects of PDX on wound repair, apoptosis, proliferation and transdifferentiation in vitro. We also investigated the effects of PDX on primary rat lung fibroblast proliferation and myofibroblast differentiation. Our result suggests PDX promotes primary AT II cells wound closure by inducing the proliferation of AT II cells and reducing the apoptosis of AT II cells induced by LPS, and promotes AT II cells transdifferentiation. Furthermore, PDX inhibits transforming growth factor‐β1 (TGF‐β1) induced fibroproliferation, fibroblast collagen production and myofibroblast transformation. Furthermore, the effects of PDX on epithelial wound healing and proliferation, fibroblast proliferation and activation partly via the ALX/ PI3K signalling pathway. These data present identify a new mechanism of PDX which targets the airway epithelial cell and fibroproliferation are potential for treatment of ARDS/ALI.

The genetic diversity of 36 rice landraces and 43 breeding materials in the upper reaches of the Yangtze River in China was studied by intragenic molecular markers of 26 starch synthesis-related loci. And research on quality traits such as the amylose content (AC), gel consistency (GC) and alkali spreading value (ASV) to analyze genetic differences in quality traits. The results showed that the number of alleles, average gene diversity and polymorphism information content values of landraces were higher than those of breeding materials. The genetic similarity coefficient (GS) of 79 rice materials ranged from 0.392 to 1, with an average of 0.757.There were significant variations in the quality traits of rice landraces and breeding materials, and the high-quality compliance rates were low, only 6.3% of the varieties have an amylose content that reached grade 1. The results of cluster analysis and population structure analysis are generally consistent; that is, the two resource types are closely related and cannot be clustered independently. This study can provide a basis for genetic improvement of rice starch quality. Make full use of the quality genetic diversity of landraces in modern breeding work, further broaden the genetic base of rice and improve rice quality.

Retinal neovascularization (RNV) is a common pathological feature in many kinds of fundus oculi diseases. Sometimes RNV can even lead to severe vision loss. Oxidative injury is one of the main predisposing factors for RNV occurrence and development. The specific mechanism may be closely related to the special structural tissues of the retina. Retinal astrocytes (RACs) are mesenchymal cells located in the retinal neuroepithelial layer. RACs have an intimate anatomical relationship with microvascular endothelial cells. They have a variety of functions, but little is known about the mechanisms by which RACs regulate the function of endothelial cells. The molecules secreted by RACs, such as exosomes, have recently received a lot of attention and may provide potential clues to address the RAC‐mediated modulation of endothelial cells. In this study, we aimed to preliminarily explore the mechanisms of how RAC exosomes generated under oxidative stress are involved in the regulation of endothelial function. Our results showed that the apoptosis and autophagy levels in RACs were positively correlated with the oxidative stress level, and the exosomes generated from RACs under normal and oxidative stress conditions had different effects on the proliferation and migration of endothelial cells. However, the effect of RACs on endothelial cell function could be markedly reversed by the autophagy inhibitor 3‐methyladenine or the exosome inhibitor GW4869. Therefore, oxidative stress can lead to increased autophagy in RACs and can further promote RACs to regulate endothelial cell function by releasing exosomes., Highlights 1.tBHP‐induced oxidative stress can increase the level of autophagy in retinal (RAC) astrocytes.2.RAC with high‐autophagy level has a completely opposite effect on HUVEC functions when compared with normal RAC.3.RACs under different states have different effects on endothelial cell functions by releasing exosomes

A new series of luminescent phosphine copper(I) complexes with cyano- and hydroxyl-substituted 2,2′-bipyridine ligands [CuI(bpy(CN)2)(P(PhX)3)2](ClO4) [X = H (1); Me (2); Cl (3)], [CuI(bpy(CN)2)(POP)](ClO4) (4), [CuI(bpy(OH)2)(PPh3)2](ClO4) (5) and [CuI(bpy(OH)2)(POP)](ClO4) (6) have been synthesized and characterized. Three of these complexes have been structurally characterized by using X-ray crystallography. The effect of the attaching –CN and –OH groups at the ortho-positions of bpy ligand was investigated. In CH2Cl2 solution, these complexes show yellow to orange phosphorescence, with the emission maxima not only sensitive to the electronic nature of the bipyridine ligands, but also considerably varied with the modification of phosphine ligands. In addition, these complexes show intense tunable green to yellow emissions in their solid state. To elucidate the electronic structures and transitions of these complexes, density functional theory (DFT) calculations on representative examples revealed that the lowest energy electronic transition associated with these complexes predominantly originates from metal-to-ligand charge transfer transitions (MLCT).

Photochemical reactions of (PPh4)[OsVI(N)(L)(CN)3] (NO2-OsN) with piperidine and pyrrolidine afforded two osmium(v) hydrazido compounds, (PPh4)[OsV(L)(CN)3(NNC5H10)] ([PPh4]1) and (PPh4)[OsV(L)(CN)3(NNC4H8)] ([PPh4]2), respectively. Their structures consist of isolated, mononuclear distorted octahedral osmium anions that are well-separated from each other by PPh4+. Their low spin S = 1/2 and L = 1 ground state was confirmed by magnetometry and DFT calculations. Interestingly, both compounds exhibit slow magnetic relaxation under a bias dc-field. These osmium(v) complexes are potentially useful building-blocks for the construction of molecule-based architectures with interesting magnetic properties. In contrast, the structurally related (PPh4)[OsIII(L)(CN)3(NH3)] ([PPh4]3), which also has a low-spin S = 1/2 ground state but with a different electronic configuration (5d5), does not exhibit slow magnetic relaxation, due to the absence of any orbital moment (L = 0). Furthermore, the structurally different osmium(v) hydrazido compound reported by Meyer, [OsV(tpy)(Cl)2(NNC5H10)](PF6) (4[PF6]), also does not exhibit slow magnetic relaxation due possibly to a change in magnetic anisotropy from axial for [PPh4]1 and [PPh4]2 to planar.

PurposeThe purpose of this study is to investigate the synergism of convection, current density distribution and additives by numerical simulation and electrochemical experiments for good throwing power (TP) of copper electro-deposition in printed circuit board (PCB) manufacture.Design/methodology/approachThe flow field of THs and current density distribution on various AR of THs are calculated and analyzed. Meanwhile, corresponding simulation is used to study the performance of plating electrolytes on TP. Two electrochemical parameters, overpotential (η) and potential difference (△η), are chosen to evaluate the electrochemical properties of different plating solutions by galvanostatic measurement and potentiodynamic cathode polarization at different rotating speeds.FindingsBy combining both the results of simulation and practical plating, these two electrochemical properties of electrolytes exhibit significant impact to the system at varied conditions. Especially, the electrolyte with higher polarizingηand △ηvalues lead to the elevated TP for AR of more than 2:1.Originality/valueThe harring cell model is built as a bridge between the theoretical and experimental study for control of uniformity of plating THs in PCB manufacturing. This dual-parameter evaluation is validated to be a promising decisive method to guide the THs plating with particular AR in industry.

One-carbon (C1) substrates such as methane and methanol have been considered as the next-generation carbon source in industrial biotechnology with the characteristics of low cost, availability, and bioconvertibility. Recently, methanotrophic bacteria naturally capable of converting C1 substrates have drawn attractive attention for their promising applications in C1-based biomanufacturing for the production of chemicals or fuels. Although genetic tools have been explored for metabolically engineered methanotroph construction, there is still a lack of efficient methods for heterologous gene expression in methanotrophs. Here, a rapid and efficient electroporation method with a high transformation efficiency was developed for a robust methanotroph of Methylomicrobium buryatense 5GB1. Based on the homologous recombination and high transformation efficiency, gene deletion and heterologous gene expression can be simultaneously achieved by direct electroporation of PCR-generated linear DNA fragments. In this study, the influence of several key parameters (competent cell preparation, electroporation condition, recovery time, and antibiotic concentration) on the transformation efficiency was investigated for optimum conditions. The maximum electroporation efficiency of 719 ± 22.5 CFU/μg DNA was reached, which presents a 10-fold improvement. By employing this method, an engineered M. buryatense 5GB1 was constructed to biosynthesize isobutyraldehyde by replacing an endogenous fadE gene in the genome with a heterologous kivd gene. This study provides a potential and efficient strategy and method to facilitate the cell factory construction of methanotrophs.

Modified composite biochar offers a cost-effective solution for the remediation of contaminated sediments; however, few studies have evaluated the effects of modified composite biochar amendment on the ecotoxicity of contaminated sediment based on benthic macroinvertebrates. A 21-day sediment toxicity test was conducted using the freshwater snail Bellamya aeruginosa to examine the intrinsic ecotoxicity of a novel KOH-modified composite biochar (KOH-CBC) and its efficacy for reducing the bioavailability, uptake, and ecotoxicity of perfluorooctanoic acid (PFOA). It was found that KOH-CBC is toxic to B. aeruginosa, which may be attributed to its high polycyclic aromatic hydrocarbons (PAHs) content and alkalinity. The addition of KOH-CBC to PFOA-contaminated sediments can markedly reduce the bioavailability and uptake of PFOA by more than 90% and 50%, respectively, and subsequently alleviate the toxicity of PFOA to B. aeruginosa by at least 30%. Increasing the KOH-CBC dosage is not beneficial for further mitigating the toxicity of PFOA-contaminated sediments. Our findings imply that KOH-CBC is a promising sorbent for the in-situ remediation of PFOA-contaminated sediments. Application of acidified KOH-CBC at a dosage of approximately 1–3% will be sufficient to control the ecotoxicity of PFOA; however, its long-term environmental effects should be further validated.

A series of blue-green emitting RuII diisocyano complexes containing 2-benzoxazol-2-ylphenolate (PBO) have been prepared. The complexes were isolated under varied reaction conditions in two isomeric forms, i.e., trans,trans,trans- (1) and cis,trans,cis- (2), with varied ligand coordination geometry above the RuII center. The photoluminescence of the isomeric complexes has been compared and tuned by the systematic variation of the electronic properties of the isocyanides. The cis,trans,cis- isomers exhibit structureless emission in the blue-green region (471-517 nm) upon excitation at λex > 400 nm in dichloromethane solution at room temperature. Both isomeric forms show similarly structured greenish emission at 499-523 nm on excitation at λex > 355 nm in a methanol/ethanol (4:1) glassy medium at 77 K. On careful comparison with the corresponding absorption and electrochemical data, it is suggested that the solution emission of the cis,trans,cis- isomers (2) at room temperature is originated from the metal-to-ligand charge transfer (MLCT), while a ligand-centered (LC) parentage is assigned for the emission in a glassy state for both isomeric forms. In line with the above experimental results, DFT calculation demonstrates the change in the nature and relative energy of the HOMOs and LUMOs with respect to the varied ligand coordination geometry and π-accepting ability of the isocyanides.

Summary: Repaglinide (RPG) is a short-acting insulin secretagogue widely prescribed for the treatment of type 2 diabetes. It boosts insulin secretion by inhibiting the pancreatic ATP-sensitive potassium channel (KATP). However, the mechanisms by which RPG binds to the KATP channel are poorly understood. Here, we describe two cryo-EM structures: the pancreatic KATP channel in complex with inhibitory RPG and adenosine-5’-(γ-thio)-triphosphate (ATPγS) at 3.3 Å and a medium-resolution structure of a RPG-bound mini SUR1 protein in which the N terminus of the inward-rectifying potassium channel 6.1 (Kir6.1) is fused to the ABC transporter module of the sulfonylurea receptor 1 (SUR1). These structures reveal the binding site of RPG in the SUR1 subunit. Furthermore, the high-resolution structure reveals the complex architecture of the ATP binding site, which is formed by both Kir6.2 and SUR1 subunits, and the domain-domain interaction interfaces. : Ding et al. report the detailed binding site and the inhibitory mechanism of the insulin secretagogue repaglinide on the pancreatic KATP channel, revealed by a 3.3 Å cryo-EM structure and electrophysiology experiments. Keywords: diabetes, KATP channel, repaglinide, glibenclamide, sulfonylurea, glinides, Kir, SUR, ABC transporter, KNtp

A series of lanthanide (Ln) compounds, [EuIII(L)2(MeOH)(H2O)](ClO4)3 (1), [TbIII(L)2(H2O)](Cl3) (2) and [MIII(L)2(NO3)](ClO4)2 (M = Eu (3); Sm (4); Tb (5); Dy (6)), have been prepared by the treatment of a neutral tetra-dentate ligand (N2,N9-dibutyl-1,10-phenanthroline-2,9-dicarboxamide, L) with various Ln(III) salts in MeOH. All of the compounds have been structurally characterized by X-ray crystallography. It is noted that the anions of the Ln(III) salts play crucial roles in the solid-state structures and the properties of the resulting complexes. In compounds 1 and 2, the metal centres are 10- and 9-coordinated, respectively, which are surrounded by two L ligands and solvent molecules. When the nitrate salts are used instead, four isostructural 10-coordinate Ln(III) compounds are obtained. The photophysical properties show that most of the compounds exhibit the characteristic emission peaks of Ln(III). Ligand L acts as a very good ‘antenna’ to sensitize the Eu(III) emission, but not for other Ln(III) emissions. The quantum yield of 3 is 75.4%, which is much higher than that of 1 (17.6%) due to the –OH oscillators of the coordinated H2O and MeOH molecules in 1. The magnetic properties of the Tb(III) compounds 2 and 5 and the Dy(III) compound 6 were investigated in detail as a natural extension of our previous study of the effect of high-coordination number on the single-ion magnet (SIM) behaviour of 3d compounds. The results show that subtle changes in the coordination environment have significant effects on the magnetic behaviour. The 9-coordinate compound 2 is not a single ion magnet (SIM), but both 10-coordinate compounds 5 and 6 exhibit field-induced SIM behaviour. It is also interesting to note that, upon the application of a small dc field, 5 exhibits two distinct relaxation processes, which is uncommon in Ln-based SIMs.

Time-resolved fluorescence lifetime imaging (FLIM) in the near-infrared region of 900–1700 nm not only allows a deep tissue penetration depth but also offers the unique benefit of the quantitative visualization of molecular events in vivo and is independent of local luminescence intensity and fluorophore concentration. Herein, we report the design of a wide-range pH sensitive molecular probe based on Yb3+ porphyrinate. The Yb3+ probe shows increasing NIR emission and lifetime with pKa values of ca. 6.6 from pH 9.0 and 5.0 and also displays an elongated lifetime from ca. 135 to 170 μs at lower pH values (5.0–1.0) due to aggregation and reduced exposure to water at low pH values. Importantly, the probe is able to monitor a wide range of in vivo gastrointestinal pH values in mice models and the potential applications in imaging-guided gastrointestinal diagnostics and therapeutics were revealed. This study shows that lifetime contrast is important for preclinical imaging; lanthanide complexes could be successfully used in the design of stimuli-responsive NIR τ probes for advanced in vivo imaging.

Near-infrared (NIR) emissive lanthanide (Ln) complexes are promising candidates for fluorescence imaging in the NIR-II region (1000–1700 nm) to combine the advantages of small organic molecules and inorganic metal ions. However, their metabolism in vivo and application in in vivo imaging are still unknown. In this work, we used water-soluble Yb3+ molecular probes with a quantum yield of ca. 10% in water, which showed a deep penetration (>3 mm) upon excitation at the Q band. One of the Yb3+ complexes, Yb-2, was successfully applied in high resolution non-invasive whole body, vasculature and lymph node imaging of small animals. The complex cleared from the body through hepatobiliary and renal systems, similar to most organic fluorophores. Importantly, we demonstrated the application of Yb-2 in fluorescence-guided sentinel lymph node surgery, showing the prospective application of lanthanide complexes as molecular probes in NIR-II whole body bioimaging and surgical operation.

Nitrite anion encapsulation was realized using molecular cavitands of decamethylcucurbit[5]urils as molecular receptors. Single crystal structural analyses showed that the receptors formed sodium-capped molecular capsules that encapsulate nitrite anions inside the cavity. The inclusion entities were proved to be existing in both solution and the solid state. Moreover, the encapsulated nitrite anions could be released and decomposed in acidic solutions.

Age-related cataract (ARC) is the most common cause of severe visual impairment and blindness. The precise mechanisms of ARC are not completely understood, but it is well accepted that oxidative damage plays an important role in the disease pathogenesis. BLM, the key enzyme of the double-strand break repair (DSBR) pathway, is part of a family of DNA unwinding enzymes and has a crucial role in multiple steps of the DNA recombination, replication and repair processes. We have recently shown that BLM-rs1063147 is initially associated with nuclear ARC in a cross-section study. Therefore, we wanted to study the effects of BLM on ARC progression. In ARC patients, BLM transcription in lens capsules was decreased, so did the BLM protein, and after UVB irradiation, BLM mRNA and protein levels were increased in SRA01/04 cells. Upon silencing BLM in SRA01/04 cells and rat lens, cell vitality and apoptosis were altered, and the rat lens opacification was considerable. In conclusion, BLM can regulate cataract progression by influencing cell vitality and apoptosis.

Phytohormone play important roles in regulating developmental processes and signaling networks involved in plant responses to submergence stress. We studied the growth, leaf endogenous hormonal levels and related genes of two contrasting rice genotypes (IR64 and IR64-Sub1) pretreated with 1-aminocyclopropane-1-carboxylate (ACC) and paclobutrazol (PB) under submergence conditions. Submergence promoted underwater shoot elongation, chlorophyll degradation and expression of OsCIPK15, altered the leaf endogenous hormone levels, accelerated the yellowing and senescence of leaves, and decreased shoot dry weight and the plant survival rate. IR64 was more sensitive to submergence stress, showing larger increases of leaf GAs, ABA, IAA contents and the expression of OsCPS1, OsGA20ox1 and OsIAA11, which in IR64-Sub1 were significantly decreased with prolonged stress. Furthermore, IR64 showed decreased ZR content, cZOGT1 expression, GA/ABA and ZR/IAA, while IR64-Sub1 showed opposite trends. Shoot elongation, leaf yellowing and senescence, GAs and IAA contents and the expression of OsCPS1, OsGA20ox1 and OsIAA11 in submerged rice leaves were enhanced by ACC application, whereas PB treatment showed opposite effects, and the effects on underwater elongation of PB and Sub1 were clearly superimposable. Compared with GA/ABA, ZR/IAA was not only suitable for non-Sub1 genotypes, but also more accurate in reflecting the submergence characteristics in IR64-Sub1. These findings improve our understanding of the intricate web of connections between plant hormones that regulate physiological responses to stress.

TRPC5 channel is a nonselective cation channel that participates in diverse physiological processes. TRPC5 inhibitors show promise in the treatment of anxiety disorder, depression, and kidney disease. However, the binding sites and inhibitory mechanism of TRPC5 inhibitors remain elusive. Here, we present the cryo-EM structures of human TRPC5 in complex with two distinct inhibitors, namely clemizole and HC-070, to the resolution of 2.7 Å. The structures reveal that clemizole binds inside the voltage sensor-like domain of each subunit. In contrast, HC-070 is wedged between adjacent subunits and replaces the glycerol group of a putative diacylglycerol molecule near the extracellular side. Moreover, we found mutations in the inhibitor binding pockets altered the potency of inhibitors. These structures suggest that both clemizole and HC-070 exert the inhibitory functions by stabilizing the ion channel in a nonconductive closed state. These results pave the way for further design and optimization of inhibitors targeting human TRPC5.

AIM: To observe the protective effect of human umbilical cord mesenchymal stem cells (hucMSCs) on retinal ganglion cells (RGCs) injury in mice with acute ocular hypertension (AOH). METHODS: Fifty-six adult male C57BL/6 mice were randomly divided into four groups: normal group, AOH group, hucMSCs group, normal saline (NS) group. Left eye of mice was induced by 90 mm Hg intraocular pressure for 1h to establish AOH model. hucMSCs 1×105/µL, 1 µL or NS 1 µL was injected into the vitreous body the next day. CM-Dil fluorescent dye was used to label the 3rd generation of hucMSCs, for tracing the cells in the vitreous cavity of mice. Seven days after the model established, hematoxylin-eosin (HE) staining was used to observe the thickness of the inner retina layer in four groups. Numbers and loss rate of RGCs were evaluated by counting Brn-3a positive cells stained by immunofluorescencein. RESULTS: On the 7th day after AOH established, labeled hucMSCs were found in the vitreous cavity. HE staining showed that the thickness of retinal inner layer in AOH group was significantly lower than that in normal group and hucMSCs group (P0.05). Compared with AOH group, the RGCs in normal group was significantly higher; RGCs number increased in hucMSCs group and the loss rate was lower (P

Determination of the optimal fertilization method is crucial to maximize nitrogen use efficiency and yield of different rice cultivars. Side-deep fertilization with controlled-release nitrogen, in conjunction with machine transplanting and subsequent topdressing, was applied to Indica–japonica hybrid rice ‘Yongyou1540’ (YY1540) and indica hybrid rice ‘Tianyouhuazhan’ (TYHZ). Four nitrogen treatments were applied in 2018 and 2019: traditional nitrogen application with quick-release nitrogen (T1), single-dose deep fertilization at transplanting with 100% controlled-release nitrogen (T2), and deep fertilization of 70% controlled-release nitrogen and topdressing of 30% quick nitrogen at tillering (T3), or at panicle initiation (T4). Side-deep fertilization reduced the fertilizer application frequency without causing yield loss, T4 enhanced the yield of YY1540 by increasing the number of productive tillers and number of spikelets per panicle compared with T1, T2 and T3. The yield of TYHZ showed no significant difference among treatments. The T4 treatment decreased the number of tillers at the tilling peak stage and increased the percentage productive tillers and number of differentiated spikelets. Compared with the other treatments, T4 increased dry matter accumulation and leaf area index during panicle initiation and grain ripening, and contributed to enhanced nitrogen uptake and nitrogen utilization in YY1540. On average, nitrogen uptake and utilization in YY1540 were highest in T4, but no significant differences among treatments were observed in TYHZ. Dry matter accumulation and nitrogen uptake from panicle initiation to heading of YY1540 were correlated with number of spikelets per panicle, but no significant correlations were observed for TYHZ. Supplementary topdressing with quick-release nitrogen at the panicle initiation stage was required to increase yield of indica–japonica hybrid rice, whereas single-dose deep fertilization with controlled-release nitrogen is satisfactory for the indica hybrid cultivar.

Age-related cataract (ARC) is a progressive lens opacification that occurs from middle to old age. Eph-receptor tyrosinekinase-type A2 (EphA2) has been reported to be associated with ARC. This work aims to investigate the molecular mechanism of EphA2 in ARC. We treated human lens epithelial cells (SRA01/04) with different concentration of H2O2 to induce lens epithelial cell damage. Then, we found that H2O2 treatment significantly suppressed cell viability and enhanced the expression of EphA2 in the SRA01/04 cells. H2O2 treatment repressed cell viability and enhanced the levels of reactive oxygen species (ROS) in SRA01/04 cells, which was partly abolished by EphA2 up-regulation. Moreover, EphA2 overexpression reduced H2O2-induced apoptosis of SRA01/04 cells. EphA2 up-regulation caused an up-regulation of Bcl-2, and repressed the expression of Bax and Cleaved-caspase-3 in the SRA01/04 cells following H2O2 treatment. In conclusion, our data confirm that EphA2 overexpression enhances cell viability and inhibits apoptosis in the H2O2-treated SRA01/04 cells, thereby reducing H2O2-induced damage of lens epithelial cells. Thus, this work provides new insights into the mechanism of EphA2 in ARC.

Resting membrane potential determines the excitability of the cell and is essential for the cellular electrical activities. The NALCN channel mediates sodium leak currents, which positively adjust resting membrane potential towards depolarization. The NALCN channel is involved in several neurological processes and has been implicated in a spectrum of neurodevelopmental diseases. Here, we report the cryo-EM structure of rat NALCN and mouse FAM155A complex to 2.7 Å resolution. The structure reveals detailed interactions between NALCN and the extracellular cysteine-rich domain of FAM155A. We find that the non-canonical architecture of NALCN selectivity filter dictates its sodium selectivity and calcium block, and that the asymmetric arrangement of two functional voltage sensors confers the modulation by membrane potential. Moreover, mutations associated with human diseases map to the domain-domain interfaces or the pore domain of NALCN, intuitively suggesting their pathological mechanisms., The NALCN channel mediates sodium leak currents, which in turn adjusts resting membrane potential and neuronal excitability. Here the authors describe a cryo-EM structure of mammalian NALCN-FAM155A channel complex, showing how selectivity filter contributes to sodium permeation and calcium block and how the voltage sensors contribute to current modulation.

Luminescent Pb2+-based metal–organic frameworks (MOFs) belong to a new class of multifunctional molecular materials with interesting luminescence properties and potential applications within a single crystalline phase. In this mini review, we present the recent advances that have been achieved in their applications as single-phase white-light emitting materials and chemosensors in the last decade. We focus on the trends in the modification of their structures and luminescence by various bridging ligands, and subsequently their multifunctional applications, which may affect the future development of the field.

Barrier membranes have broad application prospects in guided bone regeneration (GBR), but their use in orthopedic and dental applications is severely limited by the germ-laden microenvironment and soft-hard tissue hierarchy. Thus, a novel nanocomposite multifunctionalized sandwich-like GBR membrane (SGM) with enhanced osteogenic properties and antimicrobial activities was fabricated by the sequential electrospinning of zinc oxide nanoparticle-doped silk fibroin (nZnO/SF), pure SF, and hydroxyapatite nanoparticle-doped SF (nHA/SF). SEM images demonstrated a well-developed porous three-dimensional sandwich-like hierarchical structure, while TEM, FTIR, XRD and EDX analyses confirmed that nZnO and nHA were successfully incorporated into the SF nanofibers. The water contact angle test indicated that the SGM exhibited satisfactory hydrophilicity after integration with nZnO and nHA. In vitro biological experiments proved that SGM had good cytocompatibility with MC3T3-E1 and L929 cells and promoted the differentiation and mineralization of MC3T3-E1 cells. Additionally, antibacterial assays suggested that the SGM exhibited noticeable antimicrobial activity in vitro and in vivo. Furthermore, the SGM promoted bone formation in both rat calvarial defect models and periodontal defect models. Consequently, the multifunctionalized nanofibrous SGM, which simultaneously exhibits good biocompatibility and enhanced osteogenic and antimicrobial properties, holds promise for GBR applications.

Aim To investigate the antitumor efficacy of microwave ablation combined with dendritic cell-derived exosomes (Dex) or dendritic cells (DC) in treating hepatocellular carcinoma using a tumor-bearing mouse model. Methods We used a bilateral tumor-bearing mouse model treated with MWA, MWA + DC (DC-combined group) or MWA + Dex (Dex-combined group). Following tumor ablation on one side, the tumor volume on the contralateral side was monitored. The proportions of CD8+ (cytotoxic) T cells and regulatory T (Treg) cells in the spleen were analyzed by flow cytometry, and the number of CD8+ T cells and Treg cells in tumor sites was detected by immunohistochemistry. The concentration of interleukin-10 and interferon-γ in plasma was identified using enzyme-linked immunosorbent assay. Results The combination therapy significantly inhibited tumor growth compared with MWA monotherapy. In addition, the tumor immune microenvironment was significantly improved in HCC mice in the combination therapy groups compared to MWA group demonstrated by an increased number of CD8+ T cells and a decreased number of Treg cells in tumor sites. A lower proportion of Treg cells were observed in the spleen in the combination therapy groups compared to MWA group. Moreover, the concentration of plasma IFN-γ increased, and the concentration of plasma IL-10 decreased in the combination therapy groups compared to the MWA group. However, there was no statistical difference between the Dex-combined group and the DC-combined group in the comparisons mentioned above. Conclusions Our results provide evidence that MWA combined with Dex can significantly inhibit tumor growth and improve the immune microenvironment compared to MWA alone. Furthermore, the immune-enhancing effect of Dex and DC was equivalent in our combination therapy strategy.

Summary TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) plays critical roles in B cells by promoting immunoglobulin class switching and plasma cell survival. However, its expression and function in T cells remain controversial. We show here that TACI expression can be strongly induced in murine CD4+ T cells in vitro by cytokines responsible for TH17 but not TH1 or TH2 differentiation. Frequencies and numbers of TH17 cells were elevated in TACI−/− compared with wild-type mice as well as among TACI−/− versus wild-type CD4+ T cells in mixed bone marrow chimeras, arguing for a T cell-intrinsic effect in the contribution of TACI deficiency to TH17 cell accumulation. TACI−/− mice were more susceptible to severe colitis induced by dextran sodium sulfate or adoptive T cell transfer, suggesting that TACI negatively regulates TH17 function and limits intestinal inflammation in a cell-autonomous manner. Finally, transcriptomic and biochemical analyses revealed that TACI−/− CD4+ T cells exhibited enhanced activation of TH17-promoting transcription factors NFAT, IRF4, c-MAF, and JUNB. Taken together, these findings reveal an important role of TACI in constraining TH17 pathogenicity and protecting against gut disease., Graphical Abstract, Highlights • TACI expression is induced in TH17 but not TH1 or TH2 cells differentiated in vitro • TACI−/− mice have expanded TH17 and Treg populations in various organs • TACI−/− mice have enhanced susceptibility to intestinal disease • Activation of TH17-promoting transcription factors is enhanced in TACI−/− CD4+ T cells, Immunology

Dual oxidases (DUOXs) produce hydrogen peroxide by transferring electrons from intracellular NADPH to extracellular oxygen. They are involved in many crucial biological processes and human diseases, especially in thyroid diseases. DUOXs are protein complexes co-assembled from the catalytic DUOX subunits and the auxiliary DUOXA subunits and their activities are regulated by intracellular calcium concentrations. Here, we report the cryo-EM structures of human DUOX1-DUOXA1 complex in both high-calcium and low-calcium states. These structures reveal the DUOX1 complex is a symmetric 2:2 hetero-tetramer stabilized by extensive inter-subunit interactions. Substrate NADPH and cofactor FAD are sandwiched between transmembrane domain and the cytosolic dehydrogenase domain of DUOX. In the presence of calcium ions, intracellular EF-hand modules enhance the catalytic activity of DUOX by stabilizing the dehydrogenase domain in a position that is optimal for electron transfer.

Theacrine, i.e., 1,3,7,9-tetramethyluric acid, is one of the major purine alkaloids found in leaf of a wild tea plant species Camellia kucha Hung T. Chang. Theacrine has been attracted great attentions academically owing to its diverse health benefits. Present review examines the advances in the research on the health beneficial effects of theacrine, including antioxidant effect, anti-inflammatory effect, locomotor activation and reducing fatigue effects, improving cognitive effect, hypnotic effect, ameliorating lipid metabolism and inhibiting breast cancer cell metastasis effect. The inconsistent results in this research field and further expectations were also discussed.

TRPC5 channel is a non-selective cation channel that participates diverse physiological processes. Human TRPC5 inhibitors show promise in the treatment of anxiety disorder, depression and kidney disease. Despite the high relevance of TRPC5 to human health, its inhibitor binding pockets have not been fully characterized due to the lack of structural information, which greatly hinders structure-based drug discovery. Here we show cryo-EM structures of human TRPC5 in complex with two distinct inhibitors, namely clemizole and HC-070, to the resolution of 2.7 Å. Based on the high-quality cryo-EM maps, we uncover the different binding pockets and detailed binding modes for these two inhibitors. Clemizole binds inside the voltage sensor-like domain of each subunit, while HC-070 binds close to the ion channel pore and is wedged between adjacent subunits. Both of them exert the inhibitory function by stabilizing the ion channel in a closed state. These structures provide templates for further design and optimization of inhibitors targeting human TRPC5.

The combination of chemotherapy with photodynamic therapy can lead to improved therapeutic efficiencies and reduced side effects compared to conventional chemotherapy. Chlorambucil (CHL) is a DNA alkylating agent, but problems like drug instability, “off-target” binding and in situ monitoring after administration often limit its clinical application. In this regard, we designed a new heteroleptic Ru(II) complex CHL-RuL, bearing a CHL conjugated pendant, which is desired to serve as an image-guided chemo-photodynamic combined theranostic agent. CHL-RuL shows considerable promise as a photosensitizer for two-photon excitation photodynamic therapy: strong and wide UV-Vis absorption bands centered around 400 nm, strong red emission (∼702 nm) with a long lifetime at the microsecond level, moderate singlet oxygen quantum yield, and significant two-photon absorption cross-section (118 GM). More interestingly, this chemical modification affords CHL-RuL greater cellular uptake and remarkable mitochondria accumulation in HeLa cells. Furthermore, CHL-RuL shows a slight selective cytotoxicity toward carcinoma HeLa cells over normal MRC-5 cells. MTT assay results and two-photon scanning cell imaging demonstrate that CHL-RuL exhibits obvious chemo-photodynamic dual action against HeLa cells.

We have recently reported a strongly luminescent osmium(VI) nitrido complex [OsVI(N)(NO2-L)(CN)3]− [HNO2-L = 2-(2-hydroxy-5-nitrophenyl)benzoxazole]. The excited state of this complex readily activ...

The branched-chain amino acids (BCAA) play an important role in muscle energy metabolism, and Kruppel-like factor 15 (KLF15) is an essential regulator of BCAA metabolism in muscle under nutritional deficiency. In this study, we analyzed the effect of normal feeding (starvation for 0 day), starvation for 3, 7, 10, 15 days, and refeeding for 7 days after 15 days of starvation on the expression of KLF15 and BCAA metabolism in muscle of Chinese soft-shelled turtles by a fasting-refeeding trial. The results showed that the level of KLF15 transcription was increased first and then decreased in muscle during short-term starvation, and the protein level was gradually increased. Both the mRNA and protein level of the KLF15 returned to normal feeding level after refeeding for 7 days. The changing trend of the activities of branched-chain aminotransferase (BCAT) and alanine aminotransferase (ALT) was consistent to that of KLF15 mRNA, but at the transcription level, the expression of BCAT mRNA was consistent with the change of enzyme activity as well as ALT continued to increase in muscle under starvation. In addition, BCAA content showed a trend that decreased first and then increased under starvation, while the alanine (Ala) was the contrary. The above results indicated that the regulatory role of KLF15 in BCAA catabolism of muscle in Chinese soft-shelled turtles under nutritional deficiency, which might be activated the catabolism of BCAA in muscle to provide energy and maintain the homeostasis by KLF15-BACC signaling axis.

Vitamin D regulates cell proliferation, inhibits cytokines release at sites of inflammation and reduces inflammatory responses. In this study, the aim was to investigate whether exogenous vitamin D attenuates LPS-induced lung injury via modulating epithelial cell proliferation, migration, apoptosis and epithelial mesenchymal transition (EMT). Murine and in vitro primary type II alveolar epithelial cell work were included in this study. In vivo, mice were mildly vitamin D deficient, 0.1, 1.5, 10 mg/kg 1,25(OH)2-vitamin D3 or 25(OH)-vitamin D3 was administrated by means of an intra-gastric injection for 14 days pre-intra-tracheal (IT) LPS, which remarkedly promoted alveolar epithelial type II cells proliferation, inhibited ATII cells apoptosis and inhibited EMT, with the outcome of attenuated LPS-induced lung injury. In vitro, vitamin D stimulated epithelial cell scratch wound repair, reduced primary ATII cells apoptosis as well. Vitamin D promoted primary human ATII cells proliferation through the PI3K/AKT signaling pathway and activation of vitamin D receptor (VDR). Moreover, vitamin D inhibited EMT in response to TGF-β, which was vitamin D receptor dependent. In conclusion, vitamin D attenuates lung injury via stimulating ATII cells proliferation and migration, reducing epithelial cell apoptosis and inhibits TGF-β induced EMT. Together, these results suggest that vitamin D has therapeutic potential for the resolution of ARDS.

Sterol O-acyltransferase 1 (SOAT1) is an endoplasmic reticulum (ER) resident, multi-transmembrane enzyme that belongs to the membrane-bound O-acyltransferase (MBOAT) family. It catalyzes the esterification of cholesterol to generate cholesteryl esters for cholesterol storage. SOAT1 is a target to treat several human diseases. However, its structure and mechanism remain elusive since its discovery. Here, we report the structure of human SOAT1 (hSOAT1) determined by cryo-EM. hSOAT1 is a tetramer consisted of a dimer of dimer. The structure of hSOAT1 dimer at 3.5 Å resolution reveals that a small molecule inhibitor CI-976 binds inside the catalytic chamber and blocks the accessibility of the active site residues H460, N421 and W420. Our results pave the way for future mechanistic study and rational drug design targeting hSOAT1 and other mammalian MBOAT family members., Sterol O-acyltransferase 1 (SOAT1, also named ACAT1) is an endoplasmic reticulum resident enzyme which catalyzes the esterification of cholesterol to generate cholesteryl esters. Here, authors report cryo-EM structures of human SOAT1 which reveal the binding site of the competitive inhibitor CI-976.

The methane (CH4)/oxygen (O2) gas supply ratios significantly affect the cell growth and metabolic pathways of aerobic obligate methanotrophs. However, few studies have explored the CH4/O2 ratios of the inlet gas, especially for the CH4 concentrations within the explosion range (5∼15% of CH4 in air). This study thoroughly investigated the molecular mechanisms associated with the impact of different CH4/O2 ratios on cell growth of a model type I methanotroph Methylomicrobium buryatense 5GB1 cultured at five different CH4/O2 supply molar ratios from 0.28 to 5.24, corresponding to CH4 content in gas mixture from 5% to 50%, using RNA-Seq transcriptomics approach. In the batch cultivation, the highest growth rate of 0.287 h-1 was achieved when the CH4/O2 supply molar ratio was 0.93 (15% CH4 in air), and it is crucial to keep the availability of carbon and oxygen levels balanced for optimal growth. At this ratio, genes related to methane metabolism, phosphate uptake system, and nitrogen fixation were significantly upregulated. The results indicated that the optimal CH4/O2 ratio prompted cell growth by increasing genes involved in metabolic pathways of carbon, nitrogen and phosphate utilization in M. buryatense 5GB1. Our findings provided an effective gas supply strategy for methanotrophs, which could enhance the production of key intermediates and enzymes to improve the performance of bioconversion processes using CH4 as the only carbon and energy source. This research also helps identify genes associated with the optimal CH4/O2 ratio for balancing energy metabolism and carbon flux, which could be candidate targets for future metabolic engineering practice.

Sterol O-acyltransferase 1 (SOAT1) is an endoplasmic reticulum (ER) resident, multi-transmembrane enzyme that belongs to the membrane-bound O-acyltransferase (MBOAT) family1. It catalyzes the esterification of cholesterol to generate cholesteryl esters for cholesterol storage2. SOAT1 is a target to treat several human diseases3. However, its structure and mechanism remain elusive since its discovery. Here, we report the structure of human SOAT1 (hSOAT1) determined by cryo-EM. hSOAT1 is a tetramer consisted of a dimer of dimer. The structure of hSOAT1 dimer at 3.5 Å resolution reveals that the small molecule inhibitor CI-976 binds inside the catalytic chamber and blocks the accessibility of the active site residues H460, N421 and W420. Our results pave the way for future mechanistic study and rational drug design of SOAT1 and other mammalian MBOAT family members.

Decamethonium diiodide is reported to perform the chemo- and regioselective encapsulation of para-dihalobenzenes through the competitive formation of halogen-bonded cocrystals starting from solutions that also contain ortho and meta isomers. Selective caging in the solid occurs even when an excess ortho or meta isomers, or even a mixture of them, is present in the solution. A prime matching between the size and shape of the dication and the formed dianions plays a key role in enabling the selective self-assembly, as proven by successful encapsulation of halogen-bond donors as weak as 1,4-dichlorobenzene and by the results of cocrystallization trials involving mismatching tectons. Encapsulated para-dihalobenzenes guest molecules can be removed quantitatively by heating the cocrystals under reduced pressure and be recovered as pure materials. The residual decamethonium diiodide can be recycled with no reduction in selectivity.

We examine the change in surface ozone and its precursor behavior over 20 years at four locations in western Peninsular Malaysia which have undergone urban-commercial development. Trend and correlation analyses were carried out on ozone and oxides of nitrogen observation data over the periods of 1997&ndash, 2016 as well as the decadal intervals of 1997&ndash, 2006 and 2007&ndash, 2016. Diurnal variation composites for decadal intervals were also plotted. Significant increasing ozone concentrations were observed at all locations for the 20-year period, with a range between 0.09 and 0.21 ppb yr&minus, 1. The most urbanized location (S3) showed the highest ozone trend. Decadal intervals show that not all stations record significant increasing trends of ozone, with S1 recording decreasing ozone at a rate of &minus, 0.44 ppb yr&minus, 1 during the latter decade. Correlation analysis showed that only oxides of nitrogen ratios (NO/NO2) had significant inverse relationships with ozone at all stations corresponding to control of ozone by photostationary state reactions. The diurnal composites show that decadal difference in NO/NO2 is mostly influenced by change in nitric oxide concentrations.