Development of gelatin-methacryloyl composite carriers for bone morphogenetic Protein-2 delivery: A potential strategy for spinal fusion.

To reduce the risk of nonunion after spinal fusion surgery, the in situ transplantation of bone marrow mesenchymal stem cells (BMSCs) induced toward osteogenic differentiation by bone morphogenetic protein-2 (BMP2) has been proven effective. However, the current biological agents used for transplantation have limitations, such as a short half-life and low bioavailability. To address this, our study utilized a safe and effective gelatin-methacryloyl (GelMA) as a carrier for BMP2. In vitro, experiments were conducted to observe the ability of this composite vehicle to induce osteogenic differentiation of BMSCs. The results showed that the GelMA hydrogel, with its critical properties and controlled release performance of BMP2, exhibited a slow release of BMP2 over 30 days. Moreover, the GelMA hydrogel not only enhanced the proliferation activity of BMSCs but also significantly promoted their osteogenic differentiation ability, surpassing the BMP2 effects. To investigate the potential of the GelMA-BMP2 composite vehicle, a rabbit model was employed to explore its ability to induce in situ intervertebral fusion by BMSCs. Transplantation experiments in rabbits demonstrated the effective induction of intervertebral bone fusion by the GelMA-BMP2-BMSC composite vehicle. In conclusion, the GelMA-BMP2-BMSC composite vehicle shows promising prospects in preclinical translational therapy for spinal intervertebral fusion. It addresses the limitations of current biological agents and offers a controlled release of BMP2, enhancing the proliferation and osteogenic differentiation of BMSCs.

Fighting bacteria with bacteria: A biocompatible living hydrogel patch for combating bacterial infections and promoting wound healing.

Bacterial infections are among the most critical global health challenges that seriously threaten the security of human. To address this issue, a biocompatible engineered living hydrogel patch was developed by co-embedding engineered photothermal bacteria (EM), photosensitizer (porphyrin) and reactive oxygen species amplifier (laccase) in a protein hydrogel. Remarkably, the genetice engineered bacteria can express melanin granules in vivo and this allows them to exhibit photothermal response upon being exposed to NIR-II laser (1064 nm) irradiation. Besides, electrostatically adhered tetramethylpyridinium porphyrin (TMPyP) on the bacterial surface and encapsulated laccase (Lac) in protein gel can generate highly toxic singlet oxygen (1O2) and hydroxyl radical (·OH) in the presence of visible light and lignin, respectively. Interestingly, the engineered bacteria hydrogel patch (EMTL@Gel) was successfully applied in synergistic photothermal, photodynamic and chemodynamic therapy, in which it was able to efficiently treat bacterial infection in mouse wounds and enhance wound healing. This work demonstrates the concept of "fighting bacteria with bacteria" combining bacterial engineering and material engineering into an engineered living hydrogel path that can synergistically boost the therapeutic outcome. STATEMENT OF SIGNIFICANCE: Genetically engineered bacteria produce melanin granules in vivo, exhibiting remarkable photothermal properties. These bacteria, along with a photosensitizer (TMPyP) and a reactive oxygen species amplifier (laccase), are incorporated into a biocompatible protein hydrogel patch. Under visible light, the patch generates toxic singlet oxygen (1O2) and hydroxyl radical (·OH), demonstrates outstanding synergistic effects in photothermal, photodynamic, and chemodynamic therapy, effectively treating bacterial infections and promoting wound healing in mice.

Liquid-Liquid Phase Separation-Mediated Photocatalytic Subcellular Hybrid System for Highly Efficient Hydrogen Production.

Plant chloroplasts have a highly compartmentalized interior, essential for executing photocatalytic functions. However, the construction of a photocatalytic reaction compartment similar to chloroplasts in inorganic-biological hybrid systems (IBS) has not been reported. Drawing inspiration from the compartmentalized chloroplast and the phenomenon of liquid-liquid phase separation, herein, a new strategy is first developed for constructing a photocatalytic subcellular hybrid system through liquid-liquid phase separation technology in living cells. Photosensitizers and in vivo expressed hydrogenases are designed to coassemble within the cell to create subcellular compartments for synergetic photocatalysis. This compartmentalization facilitates efficient electron transfer and light energy utilization, resulting in highly effective H2 production. The subcellular compartments hybrid system (HM/IBSCS) exhibits a nearly 87-fold increase in H2 production compared to the bare bacteria/hybrid system. Furthermore, the intracellular compartments of the photocatalytic reactor enhance the system's stability obviously, with the bacteria maintaining approximately 81% of their H2 production activity even after undergoing five cycles of photocatalytic hydrogen production. The research brings forward visionary prospects for the field of semi-artificial photosynthesis, offering new possibilities for advancements in areas such as renewable energy, biomanufacturing, and genetic engineering.

Avulsion fracture of the anterior superior iliac crest following autograft for anterior lumbar fusion: case report and literature review.

Avulsion fracture of the anterior superior iliac crest (ASIC) following autogenous bone grafting for anterior lumbar fusion (ALF) is an extremely rare complication. We describe a very rare case of avulsion fracture of the ASIC following autograft for ALF in a revision surgery for treating lumbar tuberculosis. A 68-year-old woman with lumbar tuberculosis underwent posterior debridement and posterior iliac crest bone graft fusion; however, her lumbar tuberculosis recurred 9 months after surgery. She then underwent a lumbar revision surgery, including removal of the posterior instrumentation and debridement, followed by anterior L2 corpectomy, debridement, anterior left iliac crest bone graft fusion, and internal fixation. When walking for the first time on postoperative day 3, she experienced a sharp, sudden-onset pain in the anterior iliac crest harvest area. X-ray revealed an avulsion fracture of the ASIC. Considering her failure to respond to conservative treatment for one week and large displacement of the fracture ends, an open reduction and internal fixation surgery was scheduled. Her pain symptoms were significantly relieved after the operation. Although rare, fracture of the ASIC following autograft for ALF should not be ignored. Fracture of the ASIC is usually treated conservatively. Additional surgical treatment is required only when intractable pain fails to respond to conservative treatment or when there is a large displacement of fracture ends that are not expected to heal spontaneously.

Comparison of instrumented and stand-alone lateral lumbar interbody fusion for lumbar degenerative disease: a systematic review and meta-analysis.

BACKGROUND: Both instrumented and stand-alone lateral lumbar interbody fusion (LLIF) have been widely used to treat lumbar degenerative disease. However, it remains controversial as whether posterior internal fixation is required when LLIF is performed. This meta-analysis aims to compare the radiographic and clinical results between instrumented and stand-alone LLIF. METHODS: PubMed, EMBASE and Cochrane Collaboration Library up to March 2023 were searched for studies that compared instrumented and stand-alone LLIF in the treatment of lumbar degenerative disease. The following outcomes were extracted for comparison: interbody fusion rate, cage subsidence rate, reoperation rate, restoration of disc height, segmental lordosis, lumbar lordosis, visual analog scale (VAS) scores of low-back and leg pain and Oswestry Disability Index (ODI) scores. RESULTS: 13 studies involving 1063 patients were included. The pooled results showed that instrumented LLIF had higher fusion rate (OR 2.09; 95% CI 1.16-3.75; P = 0.01), lower cage subsidence (OR 0.50; 95% CI 0.37-0.68; P < 0.001) and reoperation rate (OR 0.28; 95% CI 0.10-0.79; P = 0.02), and more restoration of disc height (MD 0.85; 95% CI 0.18-1.53; P = 0.01) than stand-alone LLIF. The ODI and VAS scores were similar between instrumented and stand-alone LLIF at the last follow-up. CONCLUSIONS: Based on this meta-analysis, instrumented LLIF is associated with higher rate of fusion, lower rate of cage subsidence and reoperation, and more restoration of disc height than stand-alone LLIF. For patients with high risk factors of cage subsidence, instrumented LLIF should be applied to reduce postoperative complications.

Denosumab, teriparatide and bisphosphonates for glucocorticoid-induced osteoporosis: a Bayesian network meta-analysis.

Background: Several medications have been used for glucocorticoids-induced osteoporosis (GIO). However, the best therapeutic option for GIO is still controversial. A Bayesian network meta-analysis was conducted to compare the efficacy and safety of denosumab, teriparatide and bisphosphonates for patients with GIO. Methods: Relevant randomized controlled trials published in PubMed, Embase, Cochrane Library and ClinicalTrials.gov up to August 2023 were searched. The following efficiency and safety outcomes were extracted for comparison: bone mineral density (BMD) percentage changes in lumbar spine, femur neck and total hip, and incidences of adverse events (AEs), serious adverse events (SAEs), vertebrae and non-vertebrae fracture. Bayesian random effects models were used for multiple treatment comparisons. Results: 11 eligible RCTs involving 2,877 patients were identified. All the six medications including alendronate, risedronate, etidronate, zoledronate, teriparatide, and denosumab and were effective in increasing BMD. Teriparatide and denosumab were more effective in improving lumbar spine and femur neck BMD, and reducing vertebrae fracture. Alendronate and denosumab were more effective in improving total hip BMD. Alendronate and teriparatide had the lowest incidences of AEs and SAEs. Conclusion: Teriparatide denosumab and the bisphosphonates are all effective in improving BMD for GIO patients. Based on this network meta-analysis, teriparatide and denosumab have higher efficiency in improving lumbar spine and femur neck BMD, and reducing vertebrae fracture. Systematic Review Registration: 10.17605/OSF.IO/2G8YA, identifier CRD42023456305.

Insecticide-mediated changes in the population and toxicity of the thrips species, Frankliniella occidentalis (Pergande) and Thrips flavus (Schrank) (Thysanoptera: Thripidae).

Frankliniella occidentalis (Pergande) and Thrips flavus (Schrank) (Thysanoptera: Thripidae) cause considerable damage to agricultural crops. In this study, we investigated the variations in the population density of these 2 thrips species in 2 sites (Dabai and Heilongtan) with different insecticide application levels. Bioassays were performed to determine the susceptibility of both thrips species to imidacloprid, abamectin, and high-bromine cyhalothrin in summer. The results showed that the F. occidentalis species were more abundant in Dabai than in Heilongtan during both winter and summer. The proportions of F. occidentalis in winter and summer were 28.32-43.35% and 61.79-76.02%, respectively. Moreover, F. occidentalis resistance against the 3 insecticides was significantly higher than that of T. flavus in both 2017 and 2019. Compared with 2017, the LC50 values of F. occidentalis populations in Dabai to imidacloprid, abamectin, and lambda-cyhalothrin increased to 100.076, 16.52, and 130.44 mg/liter, respectively. The number of F. occidentalis, reaching the proportion of 91.63% in 90 days, was significantly higher than that of the control after imidacloprid treatment. In conclusion, thrips interspecies competition is affected by the irrational use of insecticides, which may cause the replacement of native species by invasive species, thereby leading to an outbreak.

Current Advances of Atomically Dispersed Metal-Centered Nanozymes for Tumor Diagnosis and Therapy.

Nanozymes, which combine enzyme-like catalytic activity and the biological properties of nanomaterials, have been widely used in biomedical fields. Single-atom nanozymes (SANs) with atomically dispersed metal centers exhibit excellent biological catalytic activity due to the maximization of atomic utilization efficiency, unique metal coordination structures, and metal-support interaction, and their structure-activity relationship can also be clearly investigated. Therefore, they have become an emerging alternative to natural enzymes. This review summarizes the examples of nanocatalytic therapy based on SANs in tumor diagnosis and treatment in recent years, providing an overview of material classification, activity modulation, and therapeutic means. Next, we will delve into the therapeutic mechanism of SNAs in the tumor microenvironment and the advantages of synergistic multiple therapeutic modalities (e.g., chemodynamic therapy, sonodynamic therapy, photothermal therapy, chemotherapy, photodynamic therapy, sonothermal therapy, and gas therapy). Finally, this review proposes the main challenges and prospects for the future development of SANs in cancer diagnosis and therapy.

Self-Propelled Enzymatic Nanomotors from Prodrug-Skeletal Zeolitic Imidazolate Frameworks for Boosting Multimodel Cancer Therapy Efficiency.

Self-propelled nanomotors, which can autonomous propelled by harnessing others type of energy, have shown tremendous potential as drug delivery systems for cancer therapy. However, it remains challenging for nanomotors in tumor theranostics because of their structural complexity and deficient therapeutic model. Herein, glucose-fueled enzymatic nanomotors (GC6@cPt ZIFs) are developed through encapsulation of glucose oxidase (GOx), catalase (CAT), and chlorin e6 (Ce6) using cisplatin-skeletal zeolitic imidazolate frameworks (cPt ZIFs) for synergetic photochemotherapy. The GC6@cPt ZIFs nanomotors can produce O2 through enzymatic cascade reactions for propelling the self-propulsion. Trans-well chamber and multicellular tumor spheroids experiments demonstrate the deep penetration and high accumulation of GC6@cPt nanomotors. Importantly, the glucose-fueled nanomotor can release the chemotherapeutic cPt and generate reactive oxygen species under laser irradiation, and simultaneously consume intratumoral over-expressed glutathione. Mechanistically, such processes can inhibit cancer cell energy and destroy intratumoral redox balance to synergistically damage DNA and induce tumor cell apoptosis. Collectively, this work demonstrates that the self-propelled prodrug-skeleton nanomotors with oxidative stress activation can highlight a robust therapeutic capability of oxidants amplification and glutathione depletion to boost the synergetic cancer therapy efficiency.

Real-time vehicle target detection in inclement weather conditions based on YOLOv4.

As a crucial component of the autonomous driving task, the vehicle target detection algorithm directly impacts driving safety, particularly in inclement weather situations, where the detection precision and speed are significantly decreased. This paper investigated the You Only Look Once (YOLO) algorithm and proposed an enhanced YOLOv4 for real-time target detection in inclement weather conditions. The algorithm uses the Anchor-free approach to tackle the problem of YOLO preset anchor frame and poor fit. It better adapts to the detected target size, making it suitable for multi-scale target identification. The improved FPN network transmits feature maps to unanchored frames to expand the model's sensory field and maximize the utilization of model feature data. Decoupled head detecting head to increase the precision of target category and location prediction. The experimental dataset BDD-IW was created by extracting specific labeled photos from the BDD100K dataset and fogging some of them to test the proposed method's practical implications in terms of detection precision and speed in Inclement weather conditions. The proposed method is compared to advanced target detection algorithms in this dataset. Experimental results indicated that the proposed method achieved a mean average precision of 60.3%, which is 5.8 percentage points higher than the original YOLOv4; the inference speed of the algorithm is enhanced by 4.5 fps compared to the original, reaching a real-time detection speed of 69.44 fps. The robustness test results indicated that the proposed model has considerably improved the capacity to recognize targets in inclement weather conditions and has achieved high precision in real-time detection.

Discovery of new cinnamic derivatives as anti-inflammatory agents for treating acute lung injury in mice.

The blockade of the overexpression of pro-inflammatory cytokines by anti-inflammatory natural products has been proven therapeutically beneficial in the treatment of acute lung injury (ALI). Given the fact that cinnamic acid has been proven to have significant anti-inflammatory activity, we selected it as a promising lead compound to develop more effective analogs in treating ALI. Learning from the symmetric structure of curcumin, 32 new symmetric cinnamic derivatives were designed, synthesized, and evaluated for their anti-inflammatory activity. Among them, 6h not only displayed a remarkable inhibitory activity in vitro (85.9% and 65.7% for  IL-6 and TNF-α, respectively) without cytotoxicity but also possessed chemical structure stability. Furthermore, an in vivo study in mice revealed that the administration of 6h significantly attenuated lipopolysaccharide-induced ALI, providing new lead structures for the development of anti-inflammatory drugs for the treatment of ALI.

Multi-scale boron penetration toward stabilizing nickel-rich cathode.

Nickel-rich layered oxides LiNi x Co y Mn1- x - y O2 (x ≥ 0.8) have been recognized as the preferred cathode materials to develop lithium-ion batteries with high energy density (>300 Wh kg-1). However, the poor cycling stability and rate capability stemming from intergranular cracks and sluggish kinetics hinder their commercialization. To address such issues, a multi-scale boron penetration strategy is designed and applied on the polycrystalline LiNi0.83Co0.11Mn0.06O2 particles that are pre-treated with pore construction. The lithium-ion conductive lithium borate in grain gaps functions as the grain binder that can bear the strain/stress from anisotropic contraction/expansion, and provides more pathways for lithium-ion diffusion. As a result, the intergranular cracks are ameliorated and the lithium-ion diffusion kinetics is improved. Moreover, the coating layer separates the sensitive cathode surface and electrolyte, helping to suppress the parasitic reactions and related gas evolution. In addition, the enhanced structural stability is acquired by strong B-O bonds with trace boron doping. As a result, the boron-modified sample with an optimized boron content of 0.5% (B5-NCM) exhibits a higher initial discharge capacity of 205.5 mAh g-1 at 0.1C (1C = 200 mA g-1) and improved capacity retention of 81.7% after 100 cycles at 1C. Furthermore, the rate performance is distinctly enhanced by high lithium-ion conductive LBO (175.6 mAh g-1 for B5-NCM and 154.6 mAh g-1 for B0-NCM at 5C).

New strategies for the treatment of intervertebral disc degeneration: cell, exosome, gene, and tissue engineering.

Low back pain (LBP) caused by intervertebral disc (IVD) generation (IVDD) has always been an important problem that cannot be ignored. Traditional therapies have many deep-rooted and intractable complications that promote their treatment mode transfer to new therapies. This article mainly summarizes the shortcomings of traditional treatment methods and analyzes the research status and future development direction of IVDD treatment. We outlined the most promising IVDD therapies, including cell, exosome, gene, and tissue engineering therapy, especially tissue engineering therapy, which runs through the whole process of other therapies. In addition, the article focuses on the cellular, animal, and preclinical challenges faced by each therapeutic approach, as well as their respective advantages and disadvantages, to provide better ideas for relieving the IVDD patients' pain through new treatment methods.

The potential mechanisms and application prospects of non-coding RNAs in intervertebral disc degeneration.

Low back pain (LBP) is one of the most common musculoskeletal symptoms and severely affects patient quality of life. The majority of people may suffer from LBP during their life-span, which leading to huge economic burdens to family and society. According to the series of the previous studies, intervertebral disc degeneration (IDD) is considered as the major contributor resulting in LBP. Furthermore, non-coding RNAs (ncRNAs), mainly including microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), can regulate diverse cellular processes, which have been found to play pivotal roles in the development of IDD. However, the potential mechanisms of action for ncRNAs in the processes of IDD are still completely unrevealed. Therefore, it is challenging to consider ncRNAs to be used as the potential therapeutic targets for IDD. In this paper, we reviewed the current research progress and findings on ncRNAs in IDD: i). ncRNAs mainly participate in the process of IDD through regulating apoptosis of nucleus pulposus (NP) cells, metabolism of extracellular matrix (ECM) and inflammatory response; ii). the roles of miRNAs/lncRNAs/circRNAs are cross-talk in IDD development, which is similar to the network and can modulate each other; iii). ncRNAs have been attempted to combat the degenerative processes and may be promising as an efficient bio-therapeutic strategy in the future. Hence, this review systematically summarizes the principal pathomechanisms of IDD and shed light on the therapeutic potentials of ncRNAs in IDD.

Bioprinting for bone tissue engineering.

The shape transformation characteristics of four-dimensional (4D)-printed bone structures can meet the individual bone regeneration needs, while their structure can be programmed to cross-link or reassemble by stimulating responsive materials. At the same time, it can be used to design vascularized bone structures that help establish a bionic microenvironment, thus influencing cellular behavior and enhancing stem cell differentiation in the postprinting phase. These developments significantly improve conventional three-dimensional (3D)-printed bone structures with enhanced functional adaptability, providing theoretical support to fabricate bone structures to adapt to defective areas dynamically. The printing inks used are stimulus-responsive materials that enable spatiotemporal distribution, maintenance of bioactivity and cellular release for bone, vascular and neural tissue regeneration. This paper discusses the limitations of current bone defect therapies, 4D printing materials used to stimulate bone tissue engineering (e.g., hydrogels), the printing process, the printing classification and their value for clinical applications. We focus on summarizing the technical challenges faced to provide novel therapeutic implications for bone defect repair.

Comparison of Unilateral and Bilateral Percutaneous Kyphoplasty for Bone Cement Distribution and Clinical Efficacy: An Analysis Using Three-Dimensional Computed Tomography Images.

BACKGROUND: Percutaneous kyphoplasty (PKP) is an effective treatment for osteoporotic vertebral compression fractures (OVCF). Comparisons of different approaches have previously focused primarily on x-rays. Three-dimensional (3D) computed tomography (CT) enables better imaging evaluation of bone cement distribution. OBJECTIVES: To compare the CT imaging parameters and clinical efficacies of unilateral and bilateral PKP. STUDY DESIGN: This was a prospective, nonrandomized controlled study. SETTING: Department of Orthopedics from an affiliated hospital. METHODS: Seventy-two single-level OVCF patients who underwent 3D CT between 2018 and 2020 were evaluated prospectively. All patients underwent PKP and were assigned to 2 groups: unilateral PKP and bilateral PKP. Imaging outcomes were assessed by determining the cement volume, leakage, dispersion index, vertebral height (VH) and the cement volume of the noninjected and injected sides. Clinical outcomes were evaluated using the Visual Analog Scale (VAS). The correlations between the bone cement volume or dispersion index and the VAS, VH improvement rate (VHIR), or bone cement leakage were also evaluated. RESULTS: The mean follow-up time was 17.1 months. The postoperative VH and VAS in both groups were significantly improved (P < 0.05). However, there were no statistically significant differences in the cement volume, leakage or dispersion index, VH, or VAS between the 2 groups. No statistically significant differences in the cement volume or VH were found between the noninjected and injected sides within the unilateral group. The operative time was significantly shorter in the patients who underwent unilateral PKP. Unilateral PKP in which the bone cement did not cross the midline had a higher VAS compared with bilateral PKP. Both the bone cement volume and dispersion index displayed a positive correlation with the VHIR, but no correlation with the VAS or bone cement leakage. LIMITATIONS: This study was limited by the nonrandomized design, small sample size, and short follow-up period. CONCLUSIONS: While unilateral PKP was as effective as bilateral PKP, it had a shorter operation time. However, the bilateral PKP approach might be followed when bone cement is distributed in only one side following the unilateral PKP procedure.

Origin of Broadband Emission and Large Stokes Shift in Antimony Trisulfide.

The antimony trisulfide (Sb2S3) has been theoretically predicted to have various merits in exploiting high-performance thin-film solar cells and attracted intense attention. However, the power conversion efficiency of Sb2S3-based solar cells is yet to be satisfactory in experiments and the origin of large open circuit voltage (VOC) loss is still a controversial question. Based on first-principles calculations, we have systematically analyzed the excited state behavior and dynamics images of carriers in Sb2S3 materials. Our calculations showed that intrinsic defects like vacancy (VSb and VS) and antisites (SbS and SSb) are energetically accessible. More importantly, we found that the sulfide vacancy-bound excitons can produce a large Stokes shift of ∼0.66 eV, which could well rationalize the experimental observations like the reduction of VOC. These new findings suggest that the performance of Sb2S3-based solar cells might be largely enhanced by avoiding sulfide vacancy defects.

Recent Development of Polydopamine Anti-Bacterial Nanomaterials.

Polydopamine (PDA), as a mussel-inspired material, exhibits numerous favorable performance characteristics, such as a simple preparation process, prominent photothermal transfer efficiency, excellent biocompatibility, outstanding drug binding ability, and strong adhesive properties, showing great potential in the biomedical field. The rapid development of this field in the past few years has engendered substantial progress in PDA antibacterial materials. This review presents recent advances in PDA-based antimicrobial materials, including the preparation methods and antibacterial mechanisms of free-standing PDA materials and PDA-based composite materials. Furthermore, the urgent challenges and future research opportunities for PDA antibacterial materials are discussed.

A first-principles study of exciton self-trapping and electric polarization in one-dimensional organic lead halide perovskites.

Revealing the origin of self-trapped excitons is a prerequisite for further improving the photoluminescence efficiency of low-dimensional organic perovskites. Here, the microscopic formation mechanism of intrinsic self-trapped excitons in one-dimensional (1D) C4N2H14PbX4 (X = Cl, Br and I) systems is investigated, and the polarization-luminescence relationship is established. Our results show that 1D-C4N2H14PbX4 has a low electronic dimension (flat band characteristics), which facilitates the formation of intrinsic self-trapped excitons. The potential well formed by local distortion of the [PbX6] octahedron is the origin of exciton self-trapping. Combined with the electronic density of states and partial charge density, we further confirmed the existence of intrinsic self-trapping excitons in 1D-C4N2H14PbX4. In addition, we found that the breaking of the central inversion symmetry will induce electric polarization, which greatly improves the transition probability of electrons. These results could potentially offer a new direction for improving the luminescence properties of 1D organic lead halide perovskites.

Design, synthesis and biological evaluation of novel chromone-maleimide hybrids as potent anti-inflammatory agents against LPS-induced acute lung injury.

Acute lung injury (ALI) is an acute inflammatory disease, which severely impacts lung function with a high lethality rate. Chromone and maleimide are very important moieties of anti-inflammatory agents. Here, forty new chromone-maleimide hybrids were readily synthesized using a Heck-type coupling strategy in good yields and were screened for their anti-inflammatory activity. A majority of these hybrids showed high inhibitory potency against LPS-stimulated release of pro-inflammatory cytokines in macrophages. Preliminary structure-activity relationship studies led to the discovery of highly potent inhibitors. Five of them were found to inhibit lipopolysaccharide (LPS)-induced IL-6 and TNF-α release in a dose-dependent manner with IC50 values in the nanomolar rang. Furthermore, in vivo administration of 5e and 5g resulted in distinctly attenuated LPS-induced ALI via inhibiting the inflammation. Thus it is evident from our study that these novel chromone-maleimide hybrids present promising therapeutic potential for ALI.