Molecularly imprinted polymer-based SERS sensing of transferrin in human serum.

Specific detection of glycoproteins such as transferrin (TRF) related to neurological diseases, hepatoma and other diseases always plays an important role in the field of disease diagnosis. We designed an antibody-free immunoassay sensing method based on molecularly imprinted polymers (MIPs) formed by the polymerization of multiple functional monomers for the sensitive and selective detection of TRF in human serum. In the sandwich surface-enhanced Raman spectroscopy (SERS) sensor, the TRF-oriented magnetic MIP nanoparticles (Fe3O4@SiO2-MIPs) served as capture units to specifically recognize TRF and 4-mercaptophenylboronic acid-functionalized gold nanorods (MPBA-Au NRs) served as SERS probes to label the targets. In order to achieve stronger interaction between the recognition cavities of the prepared MIPs and the different amino acid fragments that make up TRF, Fe3O4@SiO2-MIPs were obtained through polycondensation reactions between more silylating reagents, enhancing the specific recognition of the entire TRF protein and achieving high IF. This sensing method exhibited a good linear response to TRF within the TRF concentration range of 0.01 ng mL-1 to 1 mg mL-1 (R2 = 0.9974), and the LOD was 0.00407 ng mL-1 (S/N = 3). The good stability, reproducibility and specificity of the resulting MIP based SERS sensor were demonstrated. The determination of TRF in human serum confirmed the feasibility of the method in practical applications.

Electric Double Layer Regulator Design through a Functional Group Assembly Strategy towards Long-lasting Zinc Metal Batteries.

Regulating the electric double layer (EDL) structure of the zinc metal anode by using electrolyte additives is an efficient way to suppress interface side reactions and facilitate uniform zinc deposition. Nevertheless, there are no reports investigating the proactive design of EDL-regulating additives before the start of experiments. Herein, a functional group assembly strategy is proposed to design electrolyte additives for modulating the EDL, thereby realizing a long-lasting zinc metal anode. Specifically, by screening ten common functional groups, N, N-dimethyl-1H-imidazole-1-sulfonamide (IS) is designed by assembling an imidazole group, characterized by its high adsorption capability on the zinc anode, and a sulfone group, which exhibits strong binding with Zn2+ ions. Benefiting from the adsorption functionalization of the imidazole group, the IS molecules occupy the position of H2O in the inner Helmholtz layer of the EDL, forming a molecular protective layer to inhibit H2O-induced side reactions. Meanwhile, the sulfone group in IS, acting as a binding site to Zn2+, promotes the de-solvation of Zn2+ ions, facilitating compact zinc deposition. Consequently, the utilization of IS significantly extending the cycling stability of Zn||Zn and Zn||NaV3O8·1.5H2O full cell. This study offers an innovative approach to the design of EDL regulators for high-performance zinc metal batteries.

Spin Crossover in [Fe(qsal-5-Brq)2]+ Complexes with a Quinoline-Substituted Qsal Ligand.

Using a quinoline substituted Qsal ligand, Hqsal-5-Brq (Hqsal-5-Brq = N-(5-bromo-8-quinolyl)salicylaldimine), four FeIII complexes, [Fe(qsal-5-Brq)2]A·CH3OH (Y = NO3- (1NO3), BF4- (2BF4), PF6- (3PF6), OTf- (4OTf), were prepared and characterized. Structure analysis revealed that complex 2BF4 contained two species (2BF4(P1̅) and 2BF4(C2/c)). In these compounds except 3PF6, the [Fe(qsal-5-Brq)2]+ cations form 1D chains through π-π interactions and other weak interactions. Adjacent chains are connected to form the 2D "Chain Layer" structures and 3D structures through various supramolecular interactions. For 3PF6, a "Dimer Chain" structure is formed from the loosely connected dimers. Magnetic studies revealed that compounds 1NO3 and 2BF4(P1̅) displayed abrupt hysteretic SCO with the transition temperature T1/2↓ = 235 K, T1/2↑ = 240 K for 1NO3 and T1/2↓ = 230 K, T1/2↑ = 235 K for 2BF4(P1̅), while compounds 3PF6 and 4OTf are in the HS state. Desolvation of the complexes significantly modifies their SCO properties: the desolvated 1NO3 and 2BF4 show a gradual SCO, desolvated 3PF6 undergoes a two-step SCO, and desolvated 4OTf exhibits a hysteretic transition. Overall, this work reported the FeIII-SCO complexes of the quinoline-substituted Hqsal ligand and highlighted the potential of these ligands for the development of interesting FeIII-SCO materials.

CwJAZ4/9 negatively regulates jasmonate-mediated biosynthesis of terpenoids through interacting with CwMYC2 and confers salt tolerance in Curcuma wenyujin.

Plant JASMONATE ZIM-DOMAIN (JAZ) genes play crucial roles in regulating the biosynthesis of specialized metabolites and stressful responses. However, understanding of JAZs controlling these biological processes lags due to numerous JAZ copies. Here, we found that two leaf-specific CwJAZ4/9 genes from Curcuma wenyujin are strongly induced by methyl-jasmonate (MeJA) and negatively correlated with terpenoid biosynthesis. Yeast two-hybrid, luciferase complementation imaging and in vitro pull-down assays confirmed that CwJAZ4/9 proteins interact with CwMYC2 to form the CwJAZ4/9-CwMYC2 regulatory cascade. Furthermore, transgenic hairy roots showed that CwJAZ4/9 acts as repressors of MeJA-induced terpenoid biosynthesis by inhibiting the terpenoid pathway and jasmonate response, thus reducing terpenoid accumulation. In addition, we revealed that CwJAZ4/9 decreases salt sensitivity and sustains the growth of hairy roots under salt stress by suppressing the salt-mediated jasmonate responses. Transcriptome analysis for MeJA-mediated transgenic hairy root lines further confirmed that CwJAZ4/9 negatively regulates the terpenoid pathway genes and massively alters the expression of genes related to salt stress signaling and responses, and crosstalks of multiple phytohormones. Altogether, our results establish a genetic framework to understand how CwJAZ4/9 inhibits terpenoid biosynthesis and confers salt tolerance, which provides a potential strategy for producing high-value pharmaceutical terpenoids and improving resistant C. wenyujin varieties by a genetic approach.

Target isolation of diverse sesquiterpenoid from the stems of Daphne genkwa based on molecular networking.

Guiding by LC-MS/MS analysis and the Global Natural Products Social (GNPS) Molecular Networking, three undescribed sesquiterpenoids, stedapgens A-C, and two known analogues were discovered in the barks of Daphne genkwa Sieb. et Zucc. The structures were determined by analysis of their spectroscopic data and quantum-chemical calculations. All the isolated novel compounds were tested for their acetylcholinesterase inhibitory activities with IC50 = 0.754 ± 0.059, 0.696 ± 0.026, and 0.337 ± 0.023 µg/ml. Among them, stedapgen A displayed promising inhibitory activities against AChE, and the binding sites were predicted by molecular docking.

Combination of DCE-MRI and NME-DWI via Deep Neural Network for Predicting Breast Cancer Molecular Subtypes.

BACKGROUND: To explore whether the combination of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and nonmono-exponential (NME) model-based diffusion-weighted imaging (DWI) via deep neural network (DNN) can improve the prediction of breast cancer molecular subtypes compared to either imaging technique used alone. PATIENTS AND METHODS: This prospective study examined 480 breast cancers in 475 patients undergoing DCE-MRI and NME-DWI at 3.0 T. Breast cancers were classified as follows: human epidermal growth factor receptor 2 enriched (HER2-enriched), luminal A, luminal B (HER2-), luminal B (HER2+), and triple-negative subtypes. A total of 20% cases were withheld as an independent test dataset, and the remaining cases were used to train DNN with an 80% to 20% training-validation split and 5-fold cross-validation. The diagnostic accuracies of DNN in 5-way subtype classification between the DCE-MRI, NME-DWI, and their combined multiparametric-MRI datasets were compared using analysis of variance with least significant difference posthoc test. Areas under the receiver-operating characteristic curves were calculated to assess the performances of DNN in binary subtype classification between the 3 datasets. RESULTS: The 5-way classification accuracies of DNN on both DCE-MRI (0.71) and NME-DWI (0.64) were significantly lower (P < .05) than on multiparametric-MRI (0.76), while on DCE-MRI was significantly higher (P < .05) than on NME-DWI. The comparative results of binary classification between the 3 datasets were consistent with the 5-way classification. CONCLUSION: The combination of DCE-MRI and NME-DWI via DNN achieved a significant improvement in breast cancer molecular subtype prediction compared to either imaging technique used alone. Additionally, DCE-MRI outperformed NME-DWI in differentiating subtypes.

Soil amendments reduce CH4 and CO2 but increase N2O and NH3 emissions in saline-alkali paddy fields.

Limited research has been conducted on ammonia (NH3) volatilization and greenhouse gases (GHGs) emissions in saline-alkali paddy fields, along with complex interaction involving various genes (16sRNA, amoA, narG, nirK, nosZ, and nifH). This study employed mesocosm-scale experiment to investigate NH3 volatilization and GHGs emissions, focusing on bacterial communities and genic abundance, in saline-alkali paddy fields with desulfurized gypsum (DG) and organic fertilizer (OF) amendments. Compared to the control (CK) treatment, DG and OF treatments reduced methane (CH4) and carbon dioxide (CO2) emissions by 78.05 % and 26.18 %, and 65.84 % and 11.62 %, respectively. However, these treatments increased NH3 volatilization by 26.26 % and 45.23 %, and nitrous oxide (N2O) emission by 41.00 % and 12.31 %. Notably, NH3 volatilization primarily stemmed from ammonia nitrogen (NH4+-N), rather than total nitrogen (TN) in soil and water. N2O was mainly produced from nitrate nitrogen (NO3--N) in soil and water, as well as NH4+-N in water. The increase in NH3 volatilization and N2O emission in DG and OF treatments, was attributed to the reduced competition among bacterial communities, rather than the increased bacterial activity and genic copies. These findings offer valuable insights for managing nutrient loss and gaseous emissions in saline-alkali paddy fields.

[Deficiency of cathepsin K improves ischemic angiogenesis in high-fat diet fed mice].

The present study aims to investigate the effect of cathepsin K (CatK) on ischemic angiogenesis in high-fat diet fed mice. The mice were subjected to unilateral hindlimb ischemic surgery, and the ischemic blood flow was measured with a laser Doppler blood flow imager. Immunohistochemical staining was used to observe the quantity of new capillaries in the ischemic lower extremity, and Western blot was used to detect the expression of insulin receptor substrate-1 (IRS-1), p-Akt, Akt and vascular endothelial growth factor (VEGF). Firstly, the effect of high-fat diet on ischemic angiogenesis was observed in wild-type mice, which were randomly divided into control group and high-fat diet group and were fed with normal diet or 60% high-fat diet respectively for 16 weeks. The results showed the body weight and the plasma CatK concentration of the high-fat diet group was significantly increased compared with the control group (P < 0.05), and the blood flow recovery of the high-fat diet group was significantly lower than control group (P < 0.05). Then, wild-type and CatK knock out (CatK-/-) mice were both fed with high-fat diet to further observe the effect and mechanism of CatK on ischemic angiogenesis under high-fat diet. The results showed that the blood flow recovery in the CatK-/- group was significantly greater than the wild-type group, and the number of CD31 positive cells was significantly increased (P < 0.05). At the same time, the protein expression levels of IRS-1, p-Akt and VEGF in the ischemic skeletal muscle were significantly increased in the CatK-/- group compared with the wild-type group (P < 0.05). These results suggest that the deficiency of CatK improves ischemic angiogenesis in high-fat diet fed mice through IRS-1-Akt-VEGF signaling pathway.

Glutamatergic Projection from the Ventral Tegmental Area to the Zona Incerta Regulates Fear Response.

Innate defensive behavior is important for animal survival. The Vglut2+ neurons in the ventral tegmental area (VTA) have been demonstrated to play important roles in innate defensive behaviors, but the neural circuit mechanism is still unclear. Here, we find that VTA - zona incerta (ZI) glutamatergic projection is involved in regulating innate fear responses. Combining calcium signal recording and chemogentics, we find that VTA-Vglut2+ neurons respond to foot shock stimulus. Inhibition of VTA-Vglut2+ neurons reduces foot shock-evoked freezing, while chemogentic activation of these neurons results in an enhanced fear response. Using viral tracing and immunofluorescence, we show that VTA - Vglut2+ neurons send direct excitatory outputs to the ZI. Moreover, we find that the activity of VTAVglut2 - ZI projection is pivotal in modulating fear response. Together, our study reveals a new VTA - ZI glutamatergic circuit in mediating innate fear response and provides a potential target for treating post-traumatic stress disorder.

Ground-state electron transfer in all-polymer donor:acceptor blends enables aqueous processing of water-insoluble conjugated polymers.

Water-based conductive inks are vital for the sustainable manufacturing and widespread adoption of organic electronic devices. Traditional methods to produce waterborne conductive polymers involve modifying their backbone with hydrophilic side chains or using surfactants to form and stabilize aqueous nanoparticle dispersions. However, these chemical approaches are not always feasible and can lead to poor material/device performance. Here, we demonstrate that ground-state electron transfer (GSET) between donor and acceptor polymers allows the processing of water-insoluble polymers from water. This approach enables macromolecular charge-transfer salts with 10,000× higher electrical conductivities than pristine polymers, low work function, and excellent thermal/solvent stability. These waterborne conductive films have technological implications for realizing high-performance organic solar cells, with efficiency and stability superior to conventional metal oxide electron transport layers, and organic electrochemical neurons with biorealistic firing frequency. Our findings demonstrate that GSET offers a promising avenue to develop water-based conductive inks for various applications in organic electronics.

A Coordination-Driven Self-Assembly and NIR Photothermal Conversion Study of Organometallic Handcuffs.

Due to their fascinating topological structures and application prospects, coordination supramolecular complexes have continuously been studied by scientists. However, the controlled construction and property study of organometallic handcuffs remains a significant and challenging research subject in the area of supramolecular chemistry. Hence, a series of tetranuclear organometallic and heterometallic handcuffs bearing different size and metal types were rationally designed and successfully synthesized by utilizing a quadridentate pyridyl ligand (tetra-(3-pyridylphenyl)ethylene) based on three Cp*Rh (Cp* = η5-C5Me5) fragments bearing specific longitudinal dimensions and conjugated planes. These results were determined with single-crystal X-ray diffraction analysis technology, ESI-MS NMR spectroscopy, etc. Importantly, the photoquenching effect of Cp* groups and the discrepancy of intermolecular π-π stacking interactions between building block and half-sandwich fragments promote markedly different photothermal conversion results. These results will further push the synthesis of topological structures and the development of photothermal conversion materials.

Lipidomics Profiling Reveals Serum Phospholipids Associated with Albuminuria in Early Type 2 Diabetic Kidney Disease.

Early screening and administration of DKD are beneficial for renal outcomes of type 2 diabetic patients. However, the current early diagnosis using the albuminuria/creatine ratio (ACR) contains limitations. This study aimed to compare serum lipidome variation between type 2 diabetes and early DKD patients with increased albuminuria through an untargeted lipidomics method to explore the potential lipid biomarkers for DKD identification. 92 type 2 diabetic patients were enrolled and divided into two groups: DM group (ACR < 3 mg/mmol, n = 49) and early DKD group (3 mg/mmol ≤ ACR < 30 mg/mmol, n = 43). Fasting serum was analyzed through an ultraperformance liquid mass spectrometry tandem chromatography system (LC-MS). Orthogonal partial least-squares discriminant analysis (OPLS-DA) and univariate and multivariate analysis were performed to filter differentially depressed lipids. Receiver operating characteristic (ROC) curves were used to estimate the diagnostic capability of potential lipid biomarkers. We found that serum phospholipids including phosphatidylserine (PS), sphingomyelin (SM), and phosphatidylcholine (PC) were significantly upregulated in the DKD group and were highly correlated with the ACR. In addition, a panel of two phospholipids including PS(27:0)-H and PS(30:2e)-H showed good performance to help clinical lipids in early DKD identification, which increased the area under the curve (AUC) from 0.568 to 0.954. The study exhibited the serum lipidome variation in early DKD patients, and the increased phospholipids might participate in the development of albuminuria. The panel of PS(27:0)-H and PS(30:2e)-H could be a potential biomarker for DKD diagnosis.

Volatile constituents of the leaf and fruit essential oils of Litsea cubeba (Lour.) Pers. growing wild in Baoshan region, China.

The chemical composition of the essential oil from the fruits and leaves of Litsea cubeba (Lour.) Pers. (Lauraceae) growing wild in Baoshan region, Yunnan Province of China was investigated for the first time in 5.36% and 2.16% (w/w) yields, respectively, when analysed by GC and GC/MS. Ten and 25 components were identified in the fruit and leaf oils which constituted 99.15% and 99.4% of the oils. Of the fruit oil, the major components were neral (36.51%), geranial (44.23%), and citronella (8.77%). The major components of the leaf oil were linalool (67.37%), limonene (6.37%), ß-bisabolene (6.03%), neral (5.86%), and caryophyllene oxide (3.20%). The analysis of the essential oil obtained from Baoshan revealed a significant abundance of citral and linalool in the fruits and leaves, respectively. This was the first Litsea species to exhibit ß-bisabolene as the principal constituent.

Hysteretic Spin Crossover with High Transition Temperatures in Two Cobalt(II) Complexes.

Cooperative spin crossover transitions with thermal hysteresis loops are rarely observed in cobalt(II) complexes. Herein, two new mononuclear cobalt(II) complexes with hysteretic spin crossover at relatively high temperatures (from 320 to 400 K), namely, [Co(terpy-CH2OH)2]·X2 (terpy-CH2OH = 4'-(hydroxymethyl)-2,2';6',2″-terpyridine, X = SCN-(1) and SeCN- (2)), have been synthesized and characterized structurally and magnetically. Both compounds are mononuclear CoII complexes with two chelating terpy-CH2OH ligands. Magnetic measurements revealed the existence of the hysteretic SCO transitions for both complexes. For compound 1, a one-step transition with T1/2↑= 334.5 K was observed upon heating, while a two-step transition is observed upon cooling with T1/2↓(1) = 329.3 K and T1/2↓(2) = 324.1 K (at a temperature sweep rate of 5 K/min). As for compound 2, a hysteresis loop with a width of 5 K (T1/2↓ = 391.6 K and T1/2↑ = 396.6 K, at a sweep rate of 5 K/min) can be observed. Thanks to the absence of the crystallized lattice solvents, their single crystals are stable enough at high temperatures for the structure determination at both spin states, which reveals that the hysteretic SCO transitions in both complexes originate from the crystallographic phase transitions involving a thermally induced order-disorder transition of the dangling -CH2OH groups in the ligand. This work shows that the modification of the terpy ligand has an important effect on the magnetic properties of the resulting cobalt(II) complexes.

Opportunities and challenges for ribosome-inactivating proteins in traditional Chinese medicine plants.

Ribosome-inactivating proteins (RIPs) are a class of cytotoxic rRNA N-glycosylase, which widely exist in higher plants in different taxonomy, including many traditional Chinese medicinal materials and vegetables and fruits. In this paper, the traditional Chinese medicinal plants containing RIPs protein were sorted out, and their pharmacological effects and clinical applications were analyzed. Since many RIPs in traditional Chinese medicine plants exhibit antiviral and antitumor activities and show great clinical application potential, people's interest in these proteins is on the rise. This paper summarizes the possible mechanism of RIPs's anti-virus and anti-tumor effects, and discusses its potential problems and risks, laying a foundation for subsequent research on how to exert its anti-virus and anti-tumor effects.

Syntheses, Structures, and Magnetic Properties of Three Cyano-Bridged FeII-MoIII Single-Molecule Magnets.

Three new cyano-bridged FeII-MoIII complexes assembled from the [MoIII(CN)7]4- unit, FeII ions, and three pentadentate N3O2 ligands, namely {[Fe2H3(dapab)2][Mo(CN)6]}n·2H2O·3.5MeCN (1), [Fe(H2dapb)(H2O)][Fe(Hdapb)(H2O)][Mo(CN)6]·4H2O·3MeCN (2), and [Fe(H2dapba)(H2O)]2[Mo(CN)7]·6H2O (3) (H2dapab = 2,6-diacetylpyridine bis(2-aminobenzoylhydrazone), H2dapb = 2,6-diacetylpyridine bis(benzoylhydrazone), H2dapba = 2,6-diacetylpyridine bis(4-aminobenzoylhydrazone)), have been synthesized and characterized. Single-crystal structure analyses suggest that complex 1 contains a one-dimensional (1D) chain structure where two FeII ions are bridged by the in situ generated [MoIII(CN)6]3- unit through two trans-cyanide groups into trinuclear Fe2IIMoIII clusters that are further linked by the amino of the ligand into an infinite chain. Complexes 2 and 3 are cyano-bridged Fe2IIMoIII trinuclear clusters with two FeII ions connected by the [MoIII(CN)6]3- and [MoIII(CN)7]4- units, respectively. Direct current magnetic studies confirmed the ferromagnetic interactions between the cyano-bridged FeII and MoIII centers and significant easy-axis magnetic anisotropy for all three complexes. Furthermore, complexes 1-3 exhibit slow magnetic relaxation under a zero dc field, with relaxation barriers of 42.3, 21.6, and 14.4 K, respectively, making them the first examples of cyano-bridged FeII-MoIII single-molecule magnets.

Small change, big difference: A promising praziquantel derivative designated P96 with broad-spectrum antischistosomal activity for chemotherapy of schistosomiasis japonica.

BACKGROUND: Praziquantel (PZQ) has been the first line antischistosomal drug for all species of Schistosoma, and the only available drug for schistosomiasis japonica, without any alternative drugs since the 1980s. However, PZQ cannot prevent reinfection, and cannot cure schistosomiasis thoroughly because of its poor activity against juvenile schistosomes. In addition, reliance on a single drug is extremely dangerous, the development and spread of resistance to PZQ is becoming a great concern. Therefore, development of novel drug candidates for treatment and control of schistosomiasis is urgently needed. METHODOLOGYS/PRINCIPAL FINDINGS: One of the PZQ derivative christened P96 with the substitution of cyclohexyl by cyclopentyl was synthesized by School of Pharmaceutical Sciences of Shandong University. We investigated the in vitro and in vivo activities of P96 against different developmental stages of S. japonicum. Parasitological studies and scanning electron microscopy were used to study the primary action characteristics of P96 in vitro. Both mouse and rabbit models were employed to evaluate schistosomicidal efficacy of P96 in vivo. Besides calculation of worm reduction rate and egg reduction rate, quantitative real-time PCR was used to evaluate the in vivo antischistosomal activity of P96 at molecular level. In vitro, after 24h exposure, P96 demonstrated the highest activities against both juvenile and adult worm of S. japonicum in comparison to PZQ. The antischistosomal efficacy was concentration-dependent, with P96 at 50µM demonstrating the most evident schistosomicidal effect. Scanning electron microscopy demonstrated that P96 caused more severe damages to schistosomula and adult worm tegument compared to PZQ. In vivo, our results showed that P96 was effective against S. japonicum at all developmental stages. Notably, its efficacy against young stage worms was significantly improved compared to PZQ. Moreover, P96 retained the high activity comparable to PZQ against the adult worm of S. japonicum. CONCLUSIONS: P96 is a promising drug candidate for chemotherapy of schistosomiasis japonica, which has broad spectrum of action against various developmental stage, potentially addressing the deficiency of PZQ. It might be promoted as a drug candidate for use either alone or in combination with PZQ for the treatment of schistosomiasis.

Visualizing the multi-level assembly structures of conjugated molecular systems with chain-length dependent behavior.

It remains challenging to understand the structural evolution of conjugated polymers from single chains to solvated aggregates and film microstructures, although it underpins the performance of optoelectrical devices fabricated via the mainstream solution processing method. With several ensemble visual measurements, here we unravel the morphological evolution process of a model system of isoindigo-based conjugated molecules, including the hidden molecular assembly pathways, the mesoscale network formation, and their unorthodox chain dependence. Short chains show rigid chain conformations forming discrete aggregates in solution, which further grow to form a highly ordered film that exhibits poor electrical performance. In contrast, long chains exhibit flexible chain conformations, creating interlinked aggregates networks in solution, which are directly imprinted into films, forming interconnective solid-state microstructure with excellent electrical performance. Visualizing multi-level assembly structures of conjugated molecules provides a deep understanding of the inheritance of assemblies from solution to solid-state, accelerating the optimization of device fabrication.

Syntheses and magnetic properties of a bis-bidentate nitronyl nitroxide radical based on triazolopyrimidine and its metal complexes.

A novel bis-bidentate nitronyl nitroxide radical based on triazolopyrimidine, NIT-2-TrzPm (NIT-2-TrzPm = (2-(2'-triazolopyrimidine)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazol-1-oxy-3-oxide)) and six new transition metal complexes of this ligand, namely [M(hfac)2(NIT-2-TrzPm)]·CH2Cl2 (M = Mn (1Mn) and Co (2Co)), [M(hfac)2]2(NIT-2-TrzPm) (M = Mn (3Mn) and Co (4Co)), [Mn(NIT-2-TrzPm)2(MeOH)2](ClO4)2·MeOH (5Mn), and [Co(NIT-2-TrzPm)2(MeOH)2]2(ClO4)4·4MeOH (6Co) were prepared and characterized structurally and magnetically. These complexes can be selectively synthesized by controlling the reaction ratio of M(hfac)2·2H2O to the radical ligand (for 1Mn to 4Co) or using metal perchlorates as the starting materials (for 5Mn and 6Co). Single crystal X-ray crystallographic analyses confirmed that 1Mn and 2Co are isostructural 3d-2p MII-radical complexes, in which the NIT-2-TrzPm radical acts as a terminal bidentate ligand chelating to one 3d ion, while 3Mn and 4Co are isostructural 3d-2p-3d MII-radical-MII complexes with the NIT-2-TrzPm radical acting as a bridging ligand between two 3d ions. For complexes 5Mn and 6Co, two NIT-2-TrzPm ligands from the equatorial positions coordinate with the metal center to form the 2p-3d-2p structures with the axial positions occupied by two methanol molecules. Magnetic analysis on the MnII complexes revealed the existence of a strong antiferromagnetic interaction between the MnII and the NIT radical spin, while weak ferromagnetic coupling for Mn⋯Mn and Rad⋯Rad in the Mn-NIT-Mn and Rad-Mn-Rad spins was confirmed. Interestingly, although the NIT-bridged complexes 3Mn and 4Co possess significantly different magnetic anisotropy, field-induced slow magnetic relaxation can be observed in both complexes, which was assigned to the phonon bottleneck effect for 3Mn and field-induced SMM behavior for 4Co. To the best of our knowledge, 3Mn is the first example of the NIT-bridged binuclear MnII complex undergoing slow magnetic relaxation.

Aloperine alleviates lipopolysaccharide-induced acute lung injury by inhibiting NLRP3 inflammasome activation.

RATIONALE: Excessive activation of the NLRP3 inflammasome is involved in the pathological progression of acute lung injury (ALI). Aloperine (Alo) has anti-inflammatory effects in many inflammatory disease models; however, its role in ALI remains elusive. In this study, we addressed the role of Alo in NLRP3 inflammasome activation in both ALI mice and LPS-treated RAW264.7 cells. METHODS: The activation of the NLRP3 inflammasome in LPS-induced ALI lungs was investigated in C57BL/6 mice. Alo was administered in order to study its effect on NLRP3 inflammasome activation in ALI. RAW264.7 cells were used to evaluate the underlying mechanism of Alo in the activation of the NLRP3 inflammasome in vitro. RESULTS: The activation of the NLRP3 inflammasome occurs in the lungs and RAW264.7 cells under LPS stress. Alo attenuated the pathological injury of lung tissue as well as downregulates the mRNA expression of NLRP3 and pro-caspase-1 in ALI mice and LPS-stressed RAW264.7 cells. The expression of NLRP3, pro-caspase-1, and caspase-1 p10 were also significantly suppressed by Alo in vivo and in vitro. Furthermore, Alo decreased IL-1ß and IL-18 release in ALI mice and LPS-induced RAW264.7 cells. In addition, ML385, a Nrf2 inhibitor, weakened the activity of Alo, which inhibited the activation of the NLRP3 inflammasome in vitro. CONCLUSION: Alo reduces NLRP3 inflammasome activation via the Nrf2 pathway in ALI mice.