Infiltration by monocytes of the central nervous system and its role in multiple sclerosis: reflections on therapeutic strategies

Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.

A hybrid CNN-LSTM model for diagnosing rice nutrient levels at the rice panicle initiation stage

Nitrogen(N)and potassium(K)are two key mineral nutrient elements involved in rice growth.Accurate diagnosis of N and K status is very important for the rational application of fertilizers at a specific rice growth stage.Therefore,we propose a hybrid model for diagnosing rice nutrient levels at the early panicle initiation stage(EPIS),which combines a convolutional neural network(CNN)with an attention mechanism and a long short-term memory network(LSTM).The model was validated on a large set of sequential images collected by an unmanned aerial vehicle(UAV)from rice canopies at different growth stages during a two-year experiment.Compared with VGG16,AlexNet,GoogleNet,DenseNet,and inceptionV3,ResNet101 combined with LSTM obtained the highest average accuracy of 83.81%on the dataset of Huanghuazhan(HHZ,an indica cultivar).When tested on the datasets of HHZ and Xiushui 134(XS134,a japonica rice variety)in 2021,the ResNet101-LSTM model enhanced with the squeeze-and-excitation(SE)block achieved the highest accuracies of 85.38 and 88.38%,respectively.Through the cross-dataset method,the average accuracies on the HHZ and XS134 datasets tested in 2022 were 81.25 and 82.50%,respectively,showing a good generalization.Our proposed model works with the dynamic information of different rice growth stages and can efficiently diagnose different rice nutrient status levels at EPIS,which are helpful for making practical decisions regarding rational fertilization treatments at the panicle initiation stage.

Improved observation of colonized roots reveals the regulation of arbuscule development and senescence by drought stress in the arbuscular mycorrhizae of citrus

Citrus is the typical mycorrhizal fruit tree species establishing symbiosis with arbuscular mycorrhizal (AM) fungi. However, arbuscule development and senescence in colonized citrus roots, especially in response to drought stress, remain unclear, which is mainly due to the difficulty in clearing and staining lignified roots with the conventional method. Here, we improved the observation of colonized roots of citrus plants with the sectioning method, which enabled the clear observation of AM fungal structures. Furthermore, we investigated the effects of one week of drought stress on arbuscule development and senescence with the sectioning method. Microscopy observations indicated that drought stress significantly decreased mycorrhizal colonization (F%and M%) although it did not affect plant growth performance. Fluorescence probes (WGA 488 and/or Nile red) revealed that drought stress inhibited arbuscule development by increasing the percentage of arbuscules at the early stage and decreasing the percentages of arbuscules at the midterm and mature stages. Meanwhile, drought stress accelerated arbuscule senescence, which was characterized by the increased accumulation of neutral lipids. Overall, the sectioning method developed in this study enables the in-depth investigation of arbuscule status, and drought stress can inhibit arbuscule development but accelerate arbuscule senescence in the colonized roots of citrus plants. This study paves the way to elaborately dissecting the arbuscule dynamics in the roots of fruit tree species in response to diverse abiotic stresses.

Water-responsive gel extends drug retention and facilitates skin penetration for curcumin topical delivery against psoriasis

Psoriasis is a chronic inflammatory skin disease characterized by erythema,scaling,and skin thickening.Topical drug application is recommended as the first-line treatment.Many formulation strategies have been developed and explored for enhanced topical psoriasis treatment.However,these preparations usually have low viscosity and limited retention on the skin surface,resulting in low drug delivery efficiency and poor patient satisfaction.In this study,we developed the first water-responsive gel(WRG),which has a distinct water-triggered liquid-to-gel phase transition property.Specifically,WRG was kept in a solution state in the absence of water,and the addition of water induced an immediate phase transition and resulted in a high viscosity gel.Curcumin was used as a model drug to investigate the potential of WRG in topical drug delivery against psoriasis.In vitro and in vivo data showed that WRG formulation could not only extend skin retention but also facilitate the drug permeating across the skin.In a mouse model of psoriasis,curcumin loaded WRG(CUR-WRG)effectively ameliorated the symptoms of psoriasis and exerted a potent anti-psoriasis effect by extending drug retention and facilitating drug penetration.Further mechanism study demonstrated that the anti-hyperplasia,anti-inflammation,anti-angiogenesis,anti-oxidation,and immunomodulation properties of curcumin were amplified by enhanced topical drug delivery efficiency.Notably,neglectable local or systemic toxicity was observed for CUR-WRG application.This study suggests that WRG is a promising formulation for topically psoriasis treatment.

川芎嗪通过抑制PI3K/Akt/mTOR通路诱导自噬改善糖尿病肾病大鼠肾损害

目的探讨川芎嗪对糖尿病肾病(DN)大鼠肾脏PI3K/Akt/mTOR信号通路和自噬标志蛋白LC3B表达以及尿微量白蛋白与尿肌酐比值(UACR)、肾脏病理的影响。方法采用链脲佐菌素建立DN大鼠模型,将模型大鼠随机分为模型组,川芎嗪低、中、高剂量组,厄贝沙坦组;另设正常组,每组12只。分别干预8周后,采用酶法测定尿肌酐,免疫比浊法测定尿微量白蛋白,计算UACR;取肾组织,经甲醛固定后,进行苏木精-伊红(HE)和过碘酸-雪夫(PAS)染色;通过蛋白免疫印迹法(Western blot)和免疫组化检测大鼠肾组织PI3K/Akt/mTOR信号通路以及自噬标志蛋白LC3B表达的变化。结果川芎嗪能减缓DN大鼠UACR的升高,改善其肾脏病理变化,其中川芎嗪中、高剂量组UACR显著低于模型组(P<0.05),且川芎嗪中、高剂量组与厄贝沙坦组间比较差异无统计学意义(P>0.05)。此外,川芎嗪能抑制DN大鼠肾组织p-PI3K、p-Akt、p-mTOR的表达,进而提高自噬标志蛋白LC3B的表达水平和LC3B-Ⅱ/LC3B-Ⅰ比值。结论川芎嗪能降低DN大鼠UACR的升高、改善其肾脏病理变化,发挥以上肾保护作用的机制可能与其抑制PI3K/Akt/mTOR信号通路,进而促进肾脏自噬有关。

厄贝沙坦通过诱导自噬减轻db/db小鼠肝脏脂肪变

目的:探讨厄贝沙坦对db/db小鼠脂肪肝的影响及自噬在这一过程中的作用。方法:雄性db/db小鼠24只随机分为模型组和厄贝沙坦组,另选取12只db/m小鼠作为正常对照组。各组分别干预16周后,观察体重、肝指数、血脂、肝功能以及肝脏病理的变化,检测肝组织PI3K/Akt/m TOR信号通路及自噬相关蛋白Atg-7、beclin-1和LC3B的表达情况,并利用电镜观察肝脏自噬小体的变化。结果:与模型组相比,应用厄贝沙坦干预后,db/db小鼠的体重、肝指数、血脂、丙氨酸转氨酶和天冬氨酸转氨酶与模型组相比显著降低(P<0.05),肝脏病理改变明显减轻;肝组织p-PI3K、p-Akt和p-m TOR的表达明显减少,Atg-7、beclin-1和LC3B-Ⅱ的表达明显增加,肝脏自噬小体显著增多(P<0.05)。结论:厄贝沙坦可能通过抑制PI3K/Akt/m TOR信号通路,上调自噬相关蛋白Atg-7、beclin-1和LC3B-Ⅱ表达,进而促进肝细胞自噬,减轻db/db小鼠肝脏脂肪变。

中医药治疗慢性阻塞性肺疾病血液高凝状态的进展

慢性阻塞性肺疾病是临床常见的一种慢性呼吸系统疾病,呈进行性进展,对患者的健康和生活产生严重的影响。在目前的临床治疗中,西医药治疗慢性阻塞性肺疾病的效果欠佳。本文介绍中医药治疗慢性阻塞性肺疾病血液高凝状态的进展,为临床提供探讨。

建筑物外立面改造工程造价管理与控制探讨

分析城市建筑外立面改造的种类与特点,结合具体的项目改造案例阐述外立面改造过程中所面临的问题,并针对如何进行造价控制提出相应的建议和措施。

六味地黄丸加减联合电针治疗老年高血压合并失眠的临床疗效观察

目的:探讨六味地黄丸加减联合电针治疗老年高血压合并失眠的临床疗效。方法:2019年10月-2020年10月收治老年高血压合并失眠患者60例,随机分为两组,各30例。对照组给予六味地黄丸加减治疗;试验组在六味地黄丸加减治疗基础上加用电针治疗。比较两组治疗效果。结果:试验组治疗总有效率高于对照组,差异有统计学意义(P<0.05);试验组治疗后睡眠质量评分、收缩压及舒张压均低于对照组,差异有统计学意义(P<0.05)。结论:六味地黄丸加减联合电针治疗老年高血压合并失眠的疗效显著。

BRAF^(V600E) vs. TIRADS in predicting papillary thyroid cancers in Bethesda system Ⅰ, Ⅲ, and Ⅴ nodules

Objective: Bethesda System for Reporting Thyroid Cytopathology(BSRTC) categories Ⅰ, Ⅲ, and Ⅴaccount for a significant proportion of fine needle aspiration cytology(FNAC) diagnoses. This study aimed to compare the diagnostic efficacy of BRAF^(V600E) mutation and the Thyroid Imaging Reporting and Data System(TIRADS) classification in differentiating papillary thyroid cancers(PTCs) from benign lesions among BSRTC I, III, and V nodules.Methods: A total of 472 patients with 479 nodules were enrolled in this prospective study. Ultrasound, BRAF^(V600E) mutation testing, and FNAC were performed in each nodule, followed by surgery or regular ultrasound examination.Results: In the BSRTC I category, BRAF^(V600E) showed similar sensitivity, higher specificity, and lower accuracy when compared with TIRADS. In the BSRTC III/V category, the sensitivity, specificity, and accuracy of BRAF^(V600E) were similar to those of TIRADS. In comparison to BRAF^(V600E) alone, the combination of the two methods significantly improved sensitivity(BSRTC Ⅰ:93.6% vs. 67.7%, P < 0.01; BSRTC Ⅲ: 93.8% vs. 75.0%, P < 0.01; BSRTC V: 96.0% vs. 85.3%, P < 0.001). When compared with TIRADS alone, the combination improved sensitivity in BSRTC Ⅰ nodules(93.6% vs. 74.2%, P < 0.05), increased sensitivity and decreased accuracy in BSRTC III nodules(93.8% vs. 75.0%, P < 0.01, 91.0% vs. 93.6%, P < 0.01), and improved both sensitivity and accuracy in BSRTC V nodules(96.0% vs. 82.0%, P < 0.001; 94.2% vs. 81.3%, P < 0.001).Conclusions: BRAF^(V600E) exhibited higher specificity and lower accuracy compared with TIRADS in BSRTC Ⅰ nodules, while the two methods showed similar diagnostic value in BSRTC Ⅲ/Ⅴ nodules. The combination of the two methods distinctly improved sensitivity in the diagnosis of PTCs in BSRTC Ⅰ, Ⅲ, and Ⅴ nodules.

Treatment of hepatoma with liposome-encapsulated adriamycin administered into hepatic artery of rats

AIM： To observe the therapeutic effects of liposomeencapsulated adriamycin （LADM） on hepatoma in comparison with adriamycin solution （FADM） and adriarnycin plus blank liposome （ADM ＋ BL） administered into the hepatic artery of rats. METHODS： LADM was prepared by pH gradient-driven method. Normal saline, FADM （2 mg/kg）, ADM＋BL （2 mg/kg）, and LADM （2 mg/kg） were injected via the hepatic artery in rats bearing liver W256 carcinosarcoma, which were divided into four groups randomly. The therapeutic effects were evaluated in terms of survival time, tumor enlargement ratio, and tumor necrosis degree. The difference was determined with ANOVA and Dunnett test and log rank test. RESULTS： Compared to FADM or ADM ＋ BL, LADM produced a more significant tumor inhibition （tumor volume ratio： 1.243±0.523 vs 1.883±0.708, 1.847±0.661, P 〈 0.01）, and more extensive tumor necrosis. The increased life span was prolonged significantly in rats receiving LADM compared with FADM or ADM＋BL （231.48 vs 74.66, 94.70） （P 〈 0.05）. CONCLUSION： The anticancer efficacies of adriamycin on hepatoma can be strongly improved by liposomal encapsulation through hepatic arterial administration.

Seven-senescence-associated gene signature predicts overall survival for Asian patients with hepatocellular carcinoma

BACKGROUND Cellular senescence is a recognized barrier for progression of chronic liver diseases to hepatocellular carcinoma(HCC). The expression of a cluster of genes is altered in response to environmental factors during senescence. However, it is questionable whether these genes could serve as biomarkers for HCC patients.AIM To develop a signature of senescence-associated genes(SAGs) that predicts patients' overall survival(OS) to improve prognosis prediction of HCC.METHODS SAGs were identified using two senescent cell models. Univariate COX regression analysis was performed to screen the candidate genes significantly associated with OS of HCC in a discovery cohort(GSE14520) for the least absolute shrinkage and selection operator modelling. Prognostic value of this seven-gene signature was evaluated using two independent cohorts retrieved from the GEO(GSE14520) and the Cancer Genome Atlas datasets, respectively.Time-dependent receiver operating characteristic(ROC) curve analysis was conducted to compare the predictive accuracy of the seven-SAG signature and serum α-fetoprotein(AFP).RESULTS A total of 42 SAGs were screened and seven of them, including KIF18 B, CEP55,CIT, MCM7, CDC45, EZH2, and MCM5, were used to construct a prognostic formula. All seven genes were significantly downregulated in senescent cells andupregulated in HCC tissues. Survival analysis indicated that our seven-SAG signature was strongly associated with OS, especially in Asian populations, both in discovery and validation cohorts. Moreover, time-dependent ROC curve analysis suggested the seven-gene signature had a better predictive accuracy than serum AFP in predicting HCC patients' 1-, 3-, and 5-year OS.CONCLUSION We developed a seven-SAG signature, which could predict OS of Asian HCC patients. This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.

The role of transporters in cancer redox homeostasis and cross-talk with nanomedicines

Tumor cell usually exhibits high levels of reactive oxygen species and adaptive antioxidant system due to the metabolic,genetic,and microenvironment-associated alterations.The altered redox homeostasis can promote tumor progression,development,and treatment resistance.Several membrane transporters are involved in the resetting redox homeostasis and play important roles in tumor progression.Therefore,targeting the involved transporters to disrupt the altered redox balance emerges as a viable strategy for cancer therapy.In addition,nanomedicines have drawn much attention in the past decades.Using nanomedicines to target or reset the redox homeostasis alone or combined with other therapies has brought convincing data in cancer treatment.In this review,we will introduce the altered redox balance in cancer metabolism and involved transporters,and highlight the recent advancements of redox-modulating nanomedicines for cancer treatment.

妊娠期糖尿病孕妇及2型糖尿病患者肠道菌群的特点分析

目的 探讨妊娠期糖尿病(GDM)孕妇及2型糖尿病(T2DM)患者肠道菌群的特点。方法 选取61例女性作为研究对象,将GDM孕妇纳入G组(n=15),健康孕妇纳入N组(n=18),T2DM患者纳入D组(n=14),健康女性纳入A组(n=14)。收集4组粪便样本,采用16S rDNA高通量基因测序技术进行测序,并对样品物种多样性分析、组间物种差异进行分析。结果 肠道菌群多样性分析显示,GDM孕妇与健康孕妇、T2DM患者与健康女性的Beta多样性比较,差异有统计学意义(P<0.05);在Alpha多样性上,T2DM患者的菌群丰富度与健康女性比较,差异有统计学意义(P<0.05)。GDM孕妇与健康孕妇相比,肠道菌群中厚壁菌门(Firmicutes)丰度升高,拟杆菌门(Bacteroidetes)、毛螺菌属(Lachnobacterium)丰度降低,差异有统计学意义(P<0.05)。T2DM患者与健康女性相比,肠道菌群中考拉杆菌属(Phascolarctobacterium)的丰度升高,变形菌门(Proteobacteria)、放线菌门(Actinobacteria)、罗氏菌属(Roseburia)、苏黎世杆菌属(Turicibacter)、链球菌属(Streptococcus)、放线菌属(Actinomyces)、粪球菌属(Coprococcus)、变形杆菌属(Proteus)等人体共生菌丰度降低,差异有统计学意义(P<0.05)。结论 与健康女性相比,GDM孕妇和T2DM患者的肠道菌群均存在显著差异,该研究结果可为未来临床应用肠道微生态制剂治疗GDM和T2DM提供参考依据。

Alantolactone-loaded chitosan/hyaluronic acid nanoparticles suppress psoriasis by deactivating STAT3 pathway and restricting immune cell recruitment

Psoriasis is a common chronic immune-mediated skin disease characterized by hyperproliferation and aberrant differentiation of keratinocytes and massive infiltration of inflammatory immune cells.Recent studies showed that Signal Transducer and Activator of Transcription 3(STAT3),which plays an important role in cell survival,proliferation,differentiation,angiogenesis,and immune responses,is constitutively activated in epidermal keratinocytes of human psoriatic skin lesions.In addition,STAT3 promotes the differentiation and expansion of T cells and facilitates cytokine production,thereby exacerbating the condition of psoriasis.Alantolactone(ALT)is a sesquiterpene lactone compound that could selectively suppress STAT3 activation,but its effectiveness and application in psoriasis treatment have not been determined.In this study,we developed ALT loaded chitosan/hyaluronic acid nanoparticles(CHALT),and investigated its therapeutic potential for psoriasis therapy.CHALT effectively abrogated the hyperproliferation by inducing ROS-mediated apoptosis with loss of mitochondrialmembrane potential,and also inhibited IL-6-induced STAT3 signaling activation and inflammatory reaction in HaCaT cell line.In an Imiquimod(IMQ)-induced psoriasis model,the topical treatment of psoriasis lesions with CHALT effectively attenuated the STAT3 hyperactivation within keratinocytes and ameliorated the symptoms of psoriasis.In addition,it was found that CHALT restricted the recruitment of immune cells.These results indicated that ALT-based nanoformulation CHALT holds great potential for psoriasis therapy.

A trace of Pt can significantly boost RuO_(2) for acidic water splitting

The development of highly potential electrocatalysts for acidic water electrolysis is particularly desirable for many energy‐related processes.Herein,we demonstrated a versatile strategy to activate and stabilize RuO_(2)‐based electrocatalyst for acidic water splitting by a trace of Pt,where Pt plays an essential role in promoting oxygen evolution reaction(OER),and can simultaneously act as the active site for hydrogen evolution reaction(HER).Compared with pure Ru oxide nanosheet assemblies(Ru ONAs),the“5%Pt‐containing”Ru ONAs(5%Pt‐Ru ONAs)achieve much enhanced OER activity in 0.5 and 0.05 mol/L H_(2)SO_(4),with much lower overpotentials of 227 and 234 mV at 10 mA cm^(‒2),respectively.Experimental and theoretical analyses reveal that the atomically dispersed Pt incorporating into RuO_(2)lattice is conducive to increasing the concentration of O vacancies,which effectively enhances the interaction with reaction intermediate and thus lowers the energy barrier for the formation of OOH*.Moreover,benefited from the presence of Pt,the formation of RuO_(2)is more achievable when proper annealing is applied.In addition to OER,due to the presence of active Pt,the HER performance of 5%Pt‐Ru ONAs can also be ensured,thereby realizing efficient acidic overall water splitting.Finally,the excellent activity can also be achieved without sacrificing stability.This work highlights an attractive strategy for designing active and stable RuO_(2)‐based electrocatalysts for acidic overall water splitting.

Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice

The progressive destruction of condylar cartilage is a hallmark of the temporomandibular joint(TMJ) osteoarthritis(OA);however, its mechanism is incompletely understood. Here, we show that Kindlin-2, a key focal adhesion protein, is strongly detected in cells of mandibular condylar cartilage in mice. We find that genetic ablation of Kindlin-2 in aggrecan-expressing condylar chondrocytes induces multiple spontaneous osteoarthritic lesions, including progressive cartilage loss and deformation, surface fissures, and ectopic cartilage and bone formation in TMJ. Kindlin-2 loss significantly downregulates the expression of aggrecan, Col2a1 and Proteoglycan 4(Prg4), all anabolic extracellular matrix proteins, and promotes catabolic metabolism in TMJ cartilage by inducing expression of Runx2and Mmp13 in condylar chondrocytes. Kindlin-2 loss decreases TMJ chondrocyte proliferation in condylar cartilages. Furthermore,Kindlin-2 loss promotes the release of cytochrome c as well as caspase 3 activation, and accelerates chondrocyte apoptosis in vitro and TMJ. Collectively, these findings reveal a crucial role of Kindlin-2 in condylar chondrocytes to maintain TMJ homeostasis.

Structure,variation and assembly processes of bacterial communities in different root-associated niches of tomato under periodic drought and nitrogen addition

Root-associated bacteria play a vital role in the growth and adaptation of host plants to drought stress.These bacteria can be classified as rhizoplane and rhizosphere bacteria based on their distance from the root surface.Tomato plants are often exposed to periodic drought and nitrogen(N)addition throughout their life cycle,but the impacts of these factors on the plant and root-associated bacteria are not well understood.To gain insight into this relationship,we conducted an experiment to monitor the effects of periodic drought and N addition on rhizoplane and rhizosphere bacteria of tomato plants.Drought and N addition had interactive effects on plant and soil properties,which varied with the timing of drought.There were clear divergences in community traits such as alpha diversity,beta diversity,and network topological features between the two types of bacteria.The rhizoplane bacteria showed lower alpha diversity but higher beta diversity and were more sensitive to drought and N addition than the rhizosphere bacteria.Nitrogen addition could downsize the effects of drought on rhizoplane bacterial community compositions.The higher proximity to the root might induce a community to develop more cooperation between different members to cope with plant metabolites,as revealed by the more connected and modularized community network of the rhizoplane bacteria.Drought at the seedling stage had great legacy effects on plant and soil properties.It may enhance selection,cause the dominance of deterministic processes in the assembly of rhizoplane bacteria,and reduce bacterial community network complexity.In conclusion,N addition could interact with drought in affecting tomato plants and their root-associated bacteria,depending on the timing of drought and the fineness of root niches.The higher sensitivity of rhizoplane bacteria to drought and N addition calls for more research due to their higher proximity and importance to plants in future environmental changes.

介孔氧化镁中碳量子点三重态的产生及其磷光和光催化特性

本文通过高温热解柠檬酸(CA)和Mg_(2)(OH)_(2)CO_(3)的混合物将碳量子点嵌入到介孔MgO中,并观察到室温磷光.碳量子点通过含氧官能团与MgO连接并被限制于MgO介孔中.由于碳量子点表面原子自动受限,其电子自旋角动量将改变,产生自旋三重态并可获得磷光.碳量子点与MgO的杂化复合物表现出典型的激发依赖现象,当激发波长增加时,荧光和室温磷光产生明显的红移,因此具有良好的防伪应用价值.CA在MgO中热解,使碳量子点与MgO的杂化复合物具有较高的比表面积和较宽的吸收波长.碳量子点的三重态电子延迟复合提高了载流子分离效率.因此与对照组样品对比,该复合物对有机污染物的光催化降解能力有显著提高.

Amplifying protection against acute lung injury:Targeting both inflammasome and cGAS-STING pathway by Lonicerae Japonicae Flos-Forsythiae Fructus drug pair

Objective:Acute lung injury(ALI)is characterized by inflammation and currently lacks an efficacious pharmacological intervention.The medicine combination of Lonicerae Japonicae Flos(LJF)and Forsythiae Fructus(FF)demonstrates combined properties in its anti-infective,anti-inflammatory,and therapeutic effects,particularly in alleviating respiratory symptoms.In previous studies,Chinese medicine has shown promising efficacy in lipopolysaccharides(LPS)-induced ALI.However,there have been no reports of LJF and FF pairing for lung injury.The aim of this study is to compare the efficacy of herb pair Lonicerae Japonicae Flos-Forsythiae Fructus(LF)with LJF or FF alone in the treatment of ALI,and to explore whether LJF and FF have a combined effect in the treatment of lung injury,along with the underlying mechanism involved.Methods:A total of 36 mice were divided into six groups(control,model,LJF,FF,LF,dexamethasone)based on the treatments they received after undergoing sham-operation/LPS tracheal instillation.H&E staining and pulmonary edema indexes were used to evaluate lung injury severity.Alveolar exudate cells(AECs)were counted based on cell count in bronchoalveolar lavage fluid(BALF),and neutrophil percentage in BALF was measured using flow cytometry.Myeloperoxidase(MPO)activity in BALF was measured using enzyme-linked immunosorbent assay(ELISA),while the production of IL-1β,TNF-α,and IL-6 in the lung and secretion level of them in BALF were detected by quantitative polymerase chain reaction(qPCR)and ELISA.The effect of LJF,FF,and LF on the expression of Caspase-1 and IL-1βproteins in bone marrow derived macrophages(BMDMs)supernatant was assessed using Western blot method under various inflammasome activation conditions.In addition,the concentration of IL-1βand changes in lactatedehydrogenase(LDH)release levels in BMDMs supernatant after LJF,FF,and LF administration,respectively,were measured using ELISA.Furthermore,the effects of LJF,FF and LF on STING and IRF3 phosphorylation in BMDMs were detected by Western blot,and the mRNA changes of IFN-β,TNF-α,IL-6 and CXCL10 in BMDMs were detected by qPCR.Results:LF significantly attenuated the damage to alveolar structures,pulmonary hemorrhage,and infiltration of inflammatory cells induced by LPS.This was evidenced by a decrease in lung index score and wet/dry weight ratio.Treatment with LF significantly reduced the total number of neutrophil infiltration by 75%as well as MPO activity by 88%.The efficacy of LF in reducing inflammatory factors IL-1β,TNF-α,and IL-6 in the lungs surpasses that of LJF or FF,approaching the effectiveness of dexamethasone.In BMDMs,the co-administration of 0.2 mg/mL of LJF and FF demonstrated superior inhibitory effects on the expression of nigericin-stimulated Caspase-1 and IL-1β,as well as the release levels of LDH,compared to individual treatments.Similarly,the combination of 0.5 mg/mL LJF and FF could better inhibit the phosphorylation levels of STING and IRF3 and the production of IFN-β,TNF-α,IL-6,and CXCL10 in response to ISD stimulation.Conclusion:The combination of LJF and FF increases the therapeutic effect on LPS-induced ALI,which may be mechanistically related to the combined effect inhibition of cyclic-GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)and NOD-like receptor family protein 3(NLRP3)inflammasomes pathways by LJF and FF.Our study provides new medicine candidates for the clinical treatment of ALI.