Regulation of the Nrf2/HO-1 axis by mesenchymal stem cells-derived extracellular vesicles: implications for disease treatment.

This comprehensive review inspects the therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) across multiple organ systems. Examining their impact on the integumentary, respiratory, cardiovascular, urinary, and skeletal systems, the study highlights the versatility of MSC-EVs in addressing diverse medical conditions. Key pathways, such as Nrf2/HO-1, consistently emerge as central mediators of their antioxidative and anti-inflammatory effects. From expediting diabetic wound healing to mitigating oxidative stress-induced skin injuries, alleviating acute lung injuries, and even offering solutions for conditions like myocardial infarction and renal ischemia-reperfusion injury, MSC-EVs demonstrate promising therapeutic efficacy. Their adaptability to different administration routes and identifying specific factors opens avenues for innovative regenerative strategies. This review positions MSC-EVs as promising candidates for future clinical applications, providing a comprehensive overview of their potential impact on regenerative medicine.

Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress.

OBJECTIVE: Hepatolenticular degeneration (HLD) is an autosomal recessive disorder that manifests as multiorgan damage due to impaired copper (Cu) metabolism. Female patients with HLD often experience reproductive impairments. This study investigated the protective effect of berberine against ovarian damage in toxic-milk (TX) mice, a murine model for HLD. METHODS: Mice were categorized into control group, HLD TX group (HLD group), penicillamine (Cu chelator)-treated TX group and berberine-treated TX group. Body weight, ovary weight and the number of ovulated eggs were recorded. Follicular morphology and cellular ultrastructure were examined. Total iron, ferrous iron (Fe2+) and trivalent iron (Fe3+) levels, as well as malondialdehyde (MDA), glutathione (GSH) and oxidized glutathione (GSSG), were measured in the ovaries. Western blot analysis was used to analyze the expression of proteins related to ferroptosis and endoplasmic reticulum (ER) stress. RESULTS: Ovarian tissue damage was evident in the HLD group, with a significant increase in ferroptosis and ER stress compared to the control group. This damage was inhibited by treatment with penicillamine, a Cu chelator. Compared with the HLD group, berberine increased the number of ovulations, and improved ovarian morphology and ultrastructure. Further, we found that berberine reduced total iron, Fe2+, MDA and GSSG levels, elevated GSH levels, decreased the expression of the ferroptosis marker protein prostaglandin-endoperoxide synthase 2 (PTGS2), and increased glutathione peroxidase 4 (GPX4) expression. Furthermore, berberine inhibited the expression of ER stress-associated proteins mediated by the protein kinase RNA-like ER kinase (PERK) pathway. CONCLUSION: Ferroptosis and ER stress are involved in Cu-induced ovarian damage in TX mice. Berberine ameliorates ovarian damage in HLD TX mice by inhibiting ferroptosis and ER stress. Please cite this article as: Liu QZ, Han H, Fang XR, Wang LY, Zhao D, Yin MZ, Zhang N, Jiang PY, Ji ZH, Wu LM. Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress. J Integr Med. 2024; Epub ahead of print.

Copper exposure induces inflammation and PANoptosis through the TLR4/NF-κB signaling pathway, leading to testicular damage and impaired spermatogenesis in Wilson disease.

Copper is a toxic heavy metal that causes various damage when it accumulates in the body beyond the physiological threshold. Wilson disease (WD) is an inherited disorder characterized by impaired copper metabolism. Reproductive damage in male patients with WD is gradually attracting attention. However, the underlying mechanisms of copper toxicity are unclear. In this study, we investigated the role of inflammation and PANoptosis in testicular damage and impaired spermatogenesis caused by copper deposition using the WD model toxic milk (TX) mice. Copper chelator-penicillamine and toll-like receptor 4 (TLR4) inhibitor-eritoran were used to intervene in TX mice in our animal experiment methods. Testis samples were collected from mice for further analysis. The results showed that the morphology and ultrastructure of the testis and epididymis in TX mice were damaged, and the sperm counts decreased significantly. The TLR4/nuclear factor kappa-B (NF-κB) signaling pathway was activated by copper deposition, which led to the upregulation of serum and testicular inflammatory factors in TX mice. Meanwhile, pyroptosis, apoptosis, and necroptosis were significant in the testis of TX mice. Both chelated copper or inhibited TLR4 expression markedly suppressed the TLR4/NF-κB signaling pathway, thereby reducing the expression of inflammatory factors. PANoptosis in the testis of TX mice was also reversed. Our study indicated that pathological copper exposure induces inflammation and PANoptosis through the TLR4/NF-κB signaling pathway, leading to toxic testicular damage and impaired spermatogenesis in WD.

Binary matrix factorization via collaborative neurodynamic optimization.

Binary matrix factorization is an important tool for dimension reduction for high-dimensional datasets with binary attributes and has been successfully applied in numerous areas. This paper presents a collaborative neurodynamic optimization approach to binary matrix factorization based on the original combinatorial optimization problem formulation and quadratic unconstrained binary optimization problem reformulations. The proposed approach employs multiple discrete Hopfield networks operating concurrently in search of local optima. In addition, a particle swarm optimization rule is used to reinitialize neuronal states iteratively to escape from local minima toward better ones. Experimental results on eight benchmark datasets are elaborated to demonstrate the superior performance of the proposed approach against six baseline algorithms in terms of factorization error. Additionally, the viability of the proposed approach is demonstrated for pattern discovery on three datasets.

Destabilization of Oxidized Lattice Oxygen in Layered Oxide Cathode.

Integrating anion-redox capacity with orthodox cation-redox capacity is deemed as a promising solution for high-energy-density battery cathodes surmounting the present technical bottlenecks. However, the evolution of oxidized oxygen species during the electrochemical or chemical process easily jeopardizes the reversibility of oxygen redox and remains poorly understood. Herein, we showcase the gradual conversion of the π-interacting oxygen (localized hole states on O) to the σ-interacting oxygen upon resting at a high voltage for P3-type Na0.6Li0.2Mn0.8O2 with nominally stable ribbon-like superstructure, accompanied by the O-O dimerization and the local structural reorganization. We further pinpoint an abnormal Li+ migration process from the alkali-metal layer to the transition-metal layer for desodiated P3-Na0.6Li0.2Mn0.8O2, thereby leading to a partial reconstruction of the ribbon superstructure. The high-voltage plateau of oxygen-redox cathodes is concluded to be exclusively controlled by the oxygen stabilization mechanism rather than the superstructure ordering. In addition, there exists a kinetic competition between π and σ interaction during the uninterrupted electrochemical process.

Engineering Reversible Lattice Structure for High-Capacity Co-Free Li-Rich Cathodes with Negligible Capacity Degradation.

Co-free Li-rich Mn-based cathode materials are garnering great interest because of high capacity and low cost. However, their practical application is seriously hampered by the irreversible oxygen escape and the poor cycling stability. Herein, a reversible lattice adjustment strategy is proposed by integrating O vacancies and B doping. B incorporation increases TM─O (TM: transition metal) bonding orbitals whereas decreases the antibonding orbitals. Moreover, B doping and O vacancies synergistically increase the crystal orbital bond index values enhancing the overall covalent bonding strength, which makes TM─O octahedron more resistant to damage and enables the lattice to better accommodate the deformation and reaction without irreversible fracture. Furthermore, Mott-Hubbard splitting energy is decreased due to O vacancies, facilitating electron leaps, and enhancing the lattice reactivity and capacity. Such a reversible lattice, more amenable to deformation and forestalling fracturing, markedly improves the reversibility of lattice reactions and mitigates TM migration and the irreversible oxygen redox which enables the high cycling stability and high rate capability. The modified cathode demonstrates a specific capacity of 200 mAh g-1 at 1C, amazingly sustaining the capacity for 200 cycles without capacity degradation. This finding presents a promising avenue for solving the long-term cycling issue of Li-rich cathode.

Mechanochemically Robust LiCoO2 with Ultrahigh Capacity and Prolonged Cyclability.

Pushing intercalation-type cathode materials to their theoretical capacity often suffers from fragile Li-deficient frameworks and severe lattice strain, leading to mechanical failure issues within the crystal structure and fast capacity fading. This is particularly pronounced in layered oxide cathodes because the intrinsic nature of their structures is susceptible to structural degradation with excessive Li extraction, which remains unsolved yet despite attempts involving elemental doping and surface coating strategies. Herein, a mechanochemical strengthening strategy is developed through a gradient disordering structure to address these challenges and push the LiCoO2 (LCO) layered cathode approaching the capacity limit (256 mAh g-1, up to 93% of Li utilization). This innovative approach also demonstrates exceptional cyclability and rate capability, as validated in practical Ah-level pouch full cells, surpassing the current performance benchmarks. Comprehensive characterizations with multiscale X-ray, electron diffraction, and imaging techniques unveil that the gradient disordering structure notably diminishes the anisotropic lattice strain and exhibits high fatigue resistance, even under extreme delithiation states and harsh operating voltages. Consequently, this designed LCO cathode impedes the growth and propagation of particle cracks, and mitigates irreversible phase transitions. This work sheds light on promising directions toward next-generation high-energy-density battery materials through structural chemistry design.

Zero Voltage-Degradation of Li2MnO3 with Ultrathin Amorphous Li─Mn─O Coating.

Manganese-based lithium-rich layered oxides (Mn-LLOs) are promising candidate cathode materials for lithium-ion batteries, however, the severe voltage decay during cycling is the most concern for their practical applications. Herein, an Mn-based composite nanostructure constructed Li2MnO3 (LMO@Li2MnO3) is developed via an ultrathin amorphous functional oxide LixMnOy coating at the grain surface. Due to the thin and universal LMO amorphous surface layer etched from the lithiation process by the high-concentration alkaline solution, the structural and interfacial stability of Li2MnO3 are enhanced apparently, showing the significantly improved voltage maintenance, cycle stability, and energy density. In particular, the LMO@Li2MnO3 cathode exhibits zero voltage decay over 200 cycles. Combining with ex situ spectroscopic and microscopic techniques, the Mn2+/4+ coexisted behavior of the amorphous LMO is revealed, which enables the stable electrochemistry of Li2MnO3. This work provides new possible routes for suppressing the voltage decay of Mn-LLOs by modifying with the composite functional unit construction.

A Universal Self-Propagating Synthesis of Aluminum-Based Oxyhalide Solid-State Electrolytes.

Inorganic solid-state electrolytes (SSEs) play a vital role in high-energy all-solid-state batteries (ASSBs). However, the current method of SSE preparation usually involves high-energy mechanical ball milling and/or a high-temperature annealing process, which is not suitable for practical application. Here, a facile strategy is developed to realize the scalable synthesis of cost-effective aluminum-based oxyhalide SSEs, which involves a self-propagating method by the exothermic reaction of the raw materials. This strategy enables the synthesis of various aluminum-based oxyhalide SSEs with tunable components and high ionic conductivities (over 10-3 S cm-1 at 25 °C) for different cations (Li+, Na+, Ag+). It is elucidated that the amorphous matrix, which mainly consists of various oxidized chloroaluminate species that provide numerous sites for smooth ion migration, is actually the key factor for the achieved high conductivities. Benefit from their easy synthesis, low cost, and low weight, the aluminum-based oxyhalide SSEs synthesized by our approach could further promote practical application of high-energy-density ASSBs.

Ultrafast piezocapacitive soft pressure sensors with over 10 kHz bandwidth via bonded microstructured interfaces.

Flexible pressure sensors can convert mechanical stimuli to electrical signals to interact with the surroundings, mimicking the functionality of the human skins. Piezocapacitive pressure sensors, a class of most widely used devices for artificial skins, however, often suffer from slow response-relaxation speed (tens of milliseconds) and thus fail to detect dynamic stimuli or high-frequency vibrations. Here, we show that the contact-separation behavior of the electrode-dielectric interface is an energy dissipation process that substantially determines the response-relaxation time of the sensors. We thus reduce the response and relaxation time to ~0.04 ms using a bonded microstructured interface that effectively diminishes interfacial friction and energy dissipation. The high response-relaxation speed allows the sensor to detect vibrations over 10 kHz, which enables not only dynamic force detection, but also acoustic applications. This sensor also shows negligible hysteresis to precisely track dynamic stimuli. Our work opens a path that can substantially promote the response-relaxation speed of piezocapacitive pressure sensors into submillisecond range and extend their applications in acoustic range.

Dynamical evolution of CO2 and H2O on garnet electrolyte elucidated by ambient pressure X-ray spectroscopies.

Garnet-type Li6.5La3Zr1.5Ta0.5O12 (LLZO) is considered a promising solid electrolyte, but the surface degradation in air hinders its application for all-solid-state battery. Recent studies have mainly focused on the final products of the LLZO surface reactions due to lacking of powerful in situ characterization methods. Here, we use ambient pressure X-ray spectroscopies to in situ investigate the dynamical evolution of LLZO surface in different gas environments. The newly developed ambient pressure mapping of resonant Auger spectroscopy clearly distinguishes the lithium containing species, including LiOH, Li2O, Li2CO3 and lattice oxygen. The reaction of CO2 with LLZO to form Li2CO3 is found to be a thermodynamically favored self-limiting reaction. On the contrary, the reaction of H2O with LLZO lags behind that of CO2, but intensifies at high pressure. More interestingly, the results provide direct spectroscopic evidence for the existence of Li+/H+ exchange and reveal the importance of the initial layer formed on clean electrolyte surface in determining their air stability. This work demonstrates that the newly developed in situ technologies pave a new way to investigate the oxygen evolution and surface degradation mechanism in energy materials.

Design of a delivery vehicle chitosan-based self-assembling: controlled release, high hydrophobicity, and safe treatment of plant fungal diseases.

BACKGROUND: Traditional pesticides are poorly water-soluble and suffer from low bioavailability. N-succinyl chitosan (NSCS) is a water-soluble chitosan derivative, has been recently used to encapsulate hydrophobic drugs to improve their bioavailability. However, it remains challenging to synthesize pesticides of a wide variety of water-soluble drugs and to scale up the production in a continuous manner. RESULTS: A synthetic method for preparing water-soluble nanopesticides with a polymer carrier was applied. The bioactive molecule BTL-11 was loaded into hollow NSCS to promote drug delivery, improve solubility and anti-fungal activity. The synthesized nanopesticides had well controlled sizes of 606 nm and the encapsulation rate was 80%. The release kinetics, drug toxicity and drug activity were further evaluated. The inhibitory activity of nanopesticides against Rhizoctonia solani (R. solani) was tested in vivo and in vitro. In vivo against R. solani trials revealed that BTL-11 has excellent control efficiency for cultivated rice leaf and sheath was 79.6 and 76.5%, respectively. By contrast, for BTL-11@NSCS NPs, the anti-fungal ability was strongly released and afforded significant control efficiencies of 85.9 and 81.1%. Those effects were significantly better than that of the agricultural fungicide azoxystrobin (51.5 and 66.5%). The proposed mechanism was validated by successfully predicting the synthesis outcomes. CONCLUSIONS: This study demonstrates that NSCS is a promising biocompatible carrier, which can enhance the efficacy of pesticides, synergistically improve plant disease resistance, protect crop growth, and can be used for the delivery of more insoluble pesticides.

Facile Access to High Solid Content Monodispersed Microspheres via Dual-Component Surfactants Regulation toward High-Performance Colloidal Photonic Crystals.

Monodispersed microspheres play a major role in optical science and engineering, providing ideal building blocks for structural color materials. However, the method toward high solid content (HSC) monodispersed microspheres has remained a key hurdle. Herein, a facile access to harvest monodispersed microspheres based on the emulsion polymerization mechanism is demonstrated, where anionic and nonionic surfactants are employed to achieve the electrostatic and steric dual-stabilization balance in a synergistic manner. Monodispersed poly(styrene-butyl acrylate-methacrylic acid) colloidal latex with 55 wt% HSC is achieved, which shows an enhanced self-assembly efficiency of 280% compared with the low solid content (10 wt%) latex. In addition, Ag-coated colloidal photonic crystal (Ag@CPC) coating with near-zero refractive index is achieved, presenting the characteristics of metamaterials. And an 11-fold photoluminescence emission enhancement of CdSe@ZnS quantum dots is realized by the Ag@CPC metamaterial coating. Taking advantage of high assembly efficiency, easily large-scale film-forming of the 55 wt% HSC microspheres latex, robust Ag@CPC metamaterial coatings could be easily produced for passive cooling. The coating demonstrates excellent thermal insulation performance with theoretical cooling power of 30.4 W m-2, providing practical significance for scalable CPC architecture coatings in passive cooling.

Atomically Dispersed p-Block Aluminum-Based Catalysts for Oxygen Reduction Reaction.

The main group metals are commonly perceived as catalytically inert in the context of oxygen reduction reactions (ORR) due to the delocalized valence orbitals. Regulating the local environment and structure of metal center coordinated by nitrogen ligands (M-Nx) is a promising approach to accelerate catalytic dynamics. Herein, we, for the first time, report the atomically dispersed Al catalysts coordinated with N and C atoms for 4-electron ORR. The axial coordinated pyrrolyl N group (No) is constructed in the Al-N4-No moiety to regulate the p-band structure of Al center, effectively steering the local environment and structure of the square planar Al-N4 sites, which typically exhibit too strong interaction with ORR intermediates. The dynamic covalency competition of axial Al-No and Al-O bonding could endow the Al center with moderate hybridization between Al 3p orbital and O 2p orbital, alleviating the binding energy of ORR intermediates. The as-prepared Al-N4-No electrocatalyst exhibits excellent ORR activity, selectivity, and durability, along with the rapid kinetics as demonstrated by in situ Raman spectroscopy. This work offers a fundamental comprehension of the fine regulation on p-band and guides the rational design of main-group metal-based single atom catalysts.

Amphiphilic Dendrimer as Potent Antibacterial against Drug-Resistant Bacteria in Mouse Models of Human Infectious Diseases.

Modern medicine continues to struggle against antibiotic-resistant bacterial pathogens. Among the pathogens of critical concerns are the multidrug-resistant (MDR) Pseudomonas aeruginosa, Staphylococcus aureus, and Klebsiella pneumoniae. These pathogens are major causes of nosocomial infections among immunocompromised individuals, involving major organs such as lung, skin, spleen, kidney, liver, and bloodstream. Therefore, novel approaches are direly needed. Recently, we developed an amphiphilic dendrimer DDC18-8A exhibiting high antibacterial and antibiofilm efficacy in vitro. DDC18-8A is composed of a long hydrophobic alkyl chain and a small hydrophilic poly(amidoamine) dendron bearing amine terminals, exerting its antibacterial activity by attaching and inserting itself into bacterial membranes to trigger cell lysis. Here, we examined the pharmacokinetics and in vivo toxicity as well as the antibacterial efficacy of DDC18-8A in mouse models of human infectious diseases. Remarkably, DDC18-8A significantly reduced the bacterial burden in mouse models of acute pneumonia and bacteremia by P. aeruginosa, methicillin-resistant S. aureus (MRSA), and carbapenem-resistant K. pneumoniae and neutropenic soft tissue infection by P. aeruginosa and MRSA. Most importantly, DDC18-8A outperformed pathogen-specific antibiotics against all three pathogens by achieving a similar bacterial clearance at 10-fold lower therapeutic concentrations. In addition, it showed superior stability and biodistribution in vivo, with excellent safety profiles yet without any observable abnormalities in histopathological analysis of major organs, blood serum biochemistry, and hematology. Collectively, we provide strong evidence that DDC18-8A is a promising alternative to the currently prescribed antibiotics in addressing challenges associated with nosocomial infections by MDR pathogens.

The transcription factor AP2XI-2 is a key negative regulator of Toxoplasma gondii merogony.

Sexual development in Toxoplasma gondii is a multistep process that culminates in the production of oocysts, constituting approximately 50% of human infections. However, the molecular mechanisms governing sexual commitment in this parasite remain poorly understood. Here, we demonstrate that the transcription factors AP2XI-2 and AP2XII-1 act as negative regulators, suppressing merozoite-primed pre-sexual commitment during asexual development. Depletion of AP2XI-2 in type II Pru strain induces merogony and production of mature merozoites in an alkaline medium but not in a neutral medium. In contrast, AP2XII-1-depleted Pru strain undergoes several rounds of merogony and produces merozoites in a neutral medium, with more pronounced effects observed under alkaline conditions. Additionally, we identified two additional AP2XI-2-interacting proteins involved in repressing merozoite programming. These findings underscore the intricate regulation of pre-sexual commitment by a network of factors and suggest that AP2XI-2 or AP2XII-1-depleted Pru parasites can serve as a model for studying merogony in vitro.

Are 4f-Orbitals Engaged in Covalent Bonding Between Lanthanides and Triphenylphosphine Oxide? An Oxygen K-Edge X-ray Absorption Spectroscopy and Density Functional Theory Study.

The bonding covalency between trivalent lanthanides (Ln = La, Pr, Nd, Eu, Gd) and triphenylphosphine oxide (TPPO) is studied by X-ray absorption spectra (XAS) and density functional theory (DFT) calculations on the LnCl3(TPPO)3 complexes. The O, P, and Cl K-edge XAS for the single crystals of LnCl3(TPPO)3 were collected, and the spectra were interpreted based on DFT calculations. The O and P K-edge XAS spectra showed no significant change across the Ln series in the LnCl3(TPPO)3 complexes, unlike the Cl K-edge XAS spectra. The experimental O K-edge XAS spectra suggest no mixing between the Ln 4f- and the O 2p-orbitals in the LnCl3(TPPO)3 complexes. DFT calculations indicate that the amount of the O 2p character per Ln-O bond is less than 0.1% in the Ln 4f-based orbitals in all of the LnCl3(TPPO)3 complexes. The experimental spectra and theoretical calculations demonstrate that Ln 4f-orbitals are not engaged in the covalent bonding of lanthanides with TPPO, which contrasts the involvement of U 5f-orbitals in covalent bonding in the UO2Cl2(TPPO)2 complex. Results in this work reinforce our previous speculation that bonding covalency is potentially responsible for the extractability of monodentate organophosphorus ligands toward metal ions.

NADPH oxidase 2 inhibitor GSK2795039 prevents doxorubicin-induced cardiac atrophy by attenuating cardiac sympathetic nerve terminal abnormalities and myocyte autophagy.

Doxorubicin is widely used for the treatment of human cancer, but its clinical use is limited by a cumulative dose-dependent cardiotoxicity. However, the mechanism of doxorubicin-induced cardiac atrophy and failure remains to be fully understood. In this study, we tested whether the specific NADPH oxidase 2 (Nox2) inhibitor GSK2795039 attenuates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy, leading to the amelioration of cardiac atrophy and dysfunction in chronic doxorubicin-induced cardiomyopathy. Mice were randomized to receive saline, doxorubicin (2.5 mg/kg, every other day, 6 times) or doxorubicin plus GSK2795039 (2.5 mg/kg, twice a day, 9 weeks). Left ventricular (LV) total wall thickness and LV ejection fraction were decreased in doxorubicin-treated mice compared with saline-treated mice and the decreases were prevented by the treatment of the specific Nox2 inhibitor GSK2795039. The ratio of total heart weight to tibia length and myocyte cross-sectional area were decreased in doxorubicin-treated mice, and the decreases were attenuated by the GSK2795039 treatment. In doxorubicin-treated mice, myocardial Nox2 and 4-hydroxynonenal levels were increased, myocardial expression of GAP43, tyrosine hydroxylase and norepinephrine transporter, markers of sympathetic nerve terminals, was decreased, and these changes were prevented by the GSK2795039 treatment. The ratio of LC3 II/I, a marker of autophagy, and Atg5, Atg12 and Atg12-Atg5 conjugate proteins were increased in doxorubicin-treated mice, and the increases were attenuated by the GSK2795039 treatment. These findings suggest that inhibition of Nox2 by GSK2795039 attenuates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy, thereby ameliorating cardiac atrophy and dysfunction after chronic doxorubicin treatment.

Calcineurin inhibitors in the treatment of systemic lupus erythematosus during pregnancy: A narrative review with emphasis on efficacy and safety.

Systemic lupus erythematosus (SLE) predominantly affects child-bearing women, leading to an elevated risk of maternal and fetal complications and adverse pregnancy outcomes. Since some medications can cross the placental barrier that persist a threat to both mother and fetus, the risk-benefit ratio of SLE medications should be taken into consideration during pregnancy. Calcineurin inhibitor (CNI), mainly including cyclosporin A, tacrolimus, and voclosporin, is a category of immunosuppressive agents that inhibit calcium/calmodulin-dependent phosphatase calcineurin to block T cell activation. Based on the current clinical evidence, CNI is an alternative in pregnant SLE patients with persistent disease activity (especially lupus nephritis patients) and non-responders to azathioprine. However, there is no comprehensive review that summarizes the efficacy and safety profile of CNI for SLE management during pregnancy. This review presents a summary on the utilization of CNI for SLE management during pregnancy, including the mechanism of action, gestational amelioration of lupus flare, and the balance of maternal benefit-fetal risk, which may provide more references for the management of SLE pregnancies.

Design, synthesis, and bioactivity studies of chalcone derivatives containing [1,2,4]-triazole-[4,3-a]-pyridine.

In this study, 30 chalcone derivatives containing [1,2,4]-triazole-[4,3-a]-pyridine were designed and synthesized. The results of antibacterial activity showed that EC50 values of N26 against Xoo, Pcb was 36.41, 38.53 µg/mL, respectively, which were better than those of thiodiazole copper, whose EC50 values were 60.62, 106.75 µg/mL, respectively. The bacterial inhibitory activity of N26 against Xoo was verified by SEM. Antibacterial mechanism between N26 and Xoo was preliminarily explored, the experimental results showed that when the drug concentration was 100 mg/L, N26 had a good cell membrane permeability of Xoo, and it can inhibit the production of EPS content and extracellular enzyme content to disrupt the integrity of the Xoo biofilms achieving the effect of inhibiting Xoo. At 200 mg/L, N26 can protect and inhibit the lesions of post-harvested potatoes in vivo. The activities of N1-N30 against TMV were determined with half leaf dry spot method. The EC50 values of the curative and protective activity of N22 was 77.64 and 81.55 µg/mL, respectively, which were superior to those of NNM (294.27, 175.88 µg/mL, respectively). MST experiments demonstrated that N22 (Kd = 0.0076 ± 0.0007 µmol/L) had a stronger binding ability with TMV-CP, which was much higher than that of NNM (Kd = 0.7372 ± 0.2138 µmol/L). Molecular docking results showed that N22 had a significantly higher affinity with TMV-CP than NNM.