The major histocompatibility complex participates in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by progressive loss of dopaminergic neurons in the substantia nigra and the aggregation of alpha-synuclein (α-syn). The central nervous system (CNS) has previously been considered as an immune-privileged area. However, studies have shown that the immune responses are involved in PD. The major histocompatibility complex (MHC) presents antigens from antigen-presenting cells (APCs) to T lymphocytes, immune responses will be induced. MHCs are expressed in microglia, astrocytes, and dopaminergic neurons. Single nucleotide polymorphisms in MHC are related to the risk of PD. The aggregated α-syn triggers the expression of MHCs by activating glia cells. CD4+ and CD8+ T lymphocytes responses and microglia activation are detected in brains of PD patients. In addiction immune responses further increase blood-brain barrier (BBB) permeability and T cell infiltration in PD. Thus, MHCs are involved in PD through participating in immune and inflammatory responses.

Effect of ultrasonic treatment during fermentation on the quality of fortified sweet wine.

The present study aimed to investigate the potential of ultrasonic treatment during fermentation for enhancing the quality of fortified wines with varying time and power settings. Chemical analysis and sensory evaluation were conducted to assess the impact of ultrasonic treatment on wine quality. Results showed that ultrasonic treatment could increase total anthocyanin and total phenol content, reduce anthocyanin degradation rate, and improve color stability. Moreover, ethyl carbamate content was lower in the ultrasonic group after aging compared to non-ultrasonic group. A combination of 200 W for 20 min resulted in higher sensory scores and more coordinated taste, while a combination of 400 W for 40 min produced higher levels of volatile compounds (21860.12 µg/L) leading to a richer and more elegant aroma. Therefore, ultrasound can be used as a potential technology to improve the quality of wine.

Comparison of hysterectomy cases performed by transvaginal natural orifice transluminal endoscopic surgery: A paired sample cross-sectional study.

This study aimed to investigate the feasibility, indications, and benefits of transvaginal natural orifice transluminal endoscopic surgery (v-NOTES) hysterectomy for nonmalignant gynecological diseases. The clinical data, including the baseline information and surgical conditions of 81 patients who underwent v-NOTES hysterectomy for nonmalignant gynecological diseases in a tertiary university hospital from October 2018 to August 2022, were retrospectively analyzed and compared with the total laparoscopic hysterectomy group (200 cases) and the transumbilical laparoendoscopic Single Site Surgery group (150 cases). In comparison with the other 2 groups, the highest proportion of patients in the v-NOTES group had cervical intraepithelial neoplasia. Accordingly, mean preoperative uterine volume measured by sonography was significantly smaller in the v-notes group. In the v-NOTES group, the mean number of vaginal deliveries and age were significantly higher, while the mean number of previous abdominal surgeries was lower compared to the other 2 groups. The V-NOTES group had a shorter operation time, shorter postoperative urinary catheter insertion time, earlier intestinal recovery days, shorter hospital stay, and lower visual analogue scale scores after surgery, and the differences were statistically significant. When indicated appropriately, v-NOTES hysterectomy can be a feasible and advantageous surgical modality. In particular, in comparison to the laparoendoscopic Single Site Surgery and total laparoscopic hysterectomy groups, the v-NOTES group had advantages in postoperative recovery and had more aesthetic surgical results.

Corrigendum: Establishment of tumor treating fields combined with mild hyperthermia as novel supporting therapy for pancreatic cancer.

[This corrects the article DOI: 10.3389/fonc.2021.738801.].

Cevanine-type alkaloids from the bulbs of Fritillaria unibracteata var. wabuensis and their antifibrotic activities in vitro.

Steroidal alkaloids are the main bioactive components of the bulbs of Fritillaria, which have been used as traditional Chinese medicine, known as "Beimu", for the treatment of cough for thousands of years in China. Cough and dyspnea are the most common symptoms observed in patients with pulmonary fibrosis. However, the antifibrotic activity of steroidal alkaloids has not been reported yet. In this study, two previously unreported cevanine-type steroidal alkaloids (1 and 2), four previously undescribed cevanine-type alkaloid glycosides (3-6), and 19 known steroidal alkaloids (7-25) were isolated from the bulbs of Fritillaria unibracteata var. wabuensis. The structures of these compounds were elucidated by comprehensive HRESIMS and NMR spectroscopic data analysis, as well as DP4+ NMR calculations. The biological evaluation showed that compounds 2, 7-10, 14, 15, and 17 downregulated fibrotic markers induced by transforming growth factor-ß (TGF-ß) in MRC-5 cells. Moreover, compounds 14 and 17 dose dependently inhibited TGF-ß-induced epithelial-mesenchymal transition in A549 cells, alleviated TGF-ß-induced migration and proliferation of fibroblasts, and decreased the expression of fibrotic markers, fibronectin, and N-cadherin in TGF-ß-induced MRC-5 cells. The research showed the potential of cevanine-type alkaloids as a class of natural antifibrotic agents.

Thioredoxin-1 decreases alpha-synuclein induced by MPTP through promoting autophagy-lysosome pathway.

Parkinson's disease (PD) is characterized by the formation of Lewy body in dopaminergic neurons in the substantia nigra pars compacta (SNpc). Alpha-synuclein (α-syn) is a major component of Lewy body. Autophagy eliminates damaged organelles and abnormal aggregated proteins. Thioredoxin-1 (Trx-1) is a redox regulating protein and plays roles in protecting dopaminergic neurons against neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, the relationship between Trx-1 and α-syn in PD is still unknown. In the present study, the movement disorder and dopaminergic neurotoxicity in MPTP-treated mice were improved by Trx-1 overexpression and were aggravated by Trx-1 knockdown in the SNpc in mice. The expression of α-syn was increased in the SNpc of MPTP-treated mice, which was inhibited by Trx-1 overexpression and was exacerbated in Trx-1 knockdown mice. Autophagosomes was increased under electron microscope after MPTP treatment, which were recovered in Trx-1 overexpressing mice and were further increased in Trx-1 knockdown in the SNpc in mice. The expressions of phosphatase and tensin homolog deleted on chromosome ten (PTEN)-induced putative kinase 1 (PINK1), Parkin, LC3 II and p62 were increased by MPTP, which were blocked in Trx-1 overexpressing mice and were further increased in Trx-1 knockdown mice. Cathepsin D was decreased by MPTP, which was restored in Trx-1 overexpressing mice and was further decreased in Trx-1 knockdown mice. The mRFP-GFP-LC3 green fluorescent dots were increased by 1-methyl-4-phenylpyridinium (MPP+) and further increased in Trx-1 siRNA transfected PC12 cells, while mRFP-GFP-LC3 red fluorescent dots were increased in Trx-1 overexpressing cells. These results indicate that Trx-1 may eliminate α-syn in PD mice through potentiating autophagy-lysosome pathway.

Self-sufficient nanoparticles with dual-enzyme activity trigger radical storms and activate cascade-amplified antitumor immunologic responses.

Radiotherapy (RT) can potentially induce systemic immune responses by initiating immunogenic cell death (ICD) of tumor cells. However, RT-induced antitumor immunologic responses are sporadic and insufficient against cancer metastases. Herein, we construct multifunctional self-sufficient nanoparticles (MARS) with dual-enzyme activity (GOx and peroxidase-like) to trigger radical storms and activate the cascade-amplified systemic immune responses to suppress both local tumors and metastatic relapse. In addition to limiting the Warburg effect to actualize starvation therapy, MARS catalyzes glucose to produce hydrogen peroxide (H2O2), which is then used in the Cu+-mediated Fenton-like reaction and RT sensitization. RT and chemodynamic therapy produce reactive oxygen species in the form of radical storms, which have a robust ICD impact on mobilizing the immune system. Thus, when MARS is combined with RT, potent systemic antitumor immunity can be generated by activating antigen-presenting cells, promoting dendritic cells maturation, increasing the infiltration of cytotoxic T lymphocytes, and reprogramming the immunosuppressive tumor microenvironment. Furthermore, the synergistic therapy of RT and MARS effectively suppresses local tumor growth, increases mouse longevity, and results in a 90% reduction in lung metastasis and postoperative recurrence. Overall, we provide a viable approach to treating cancer by inducing radical storms and activating cascade-amplified systemic immunity.

The role of TRPV4 in programmed cell deaths.

Programmed cell death is a major life activity of both normal development and disease. Necroptosis is early recognized as a caspase-independent form of programmed cell death followed obviously inflammation. Apoptosis is a gradually recognized mode of cell death that is characterized by a special morphological changes and unique caspase-dependent biological process. Ferroptosis, pyroptosis and autophagy are recently identified non-apoptotic regulated cell death that each has its own characteristics. The transient receptor potential vanilloid 4 (TRPV4) is a kind of nonselective calcium-permeable cation channel, which is received more and more attention in biology studies. It is widely expressed in human tissues and mainly located on the membrane of cells. Several researchers have identified that the influx Ca2+ from TRPV4 acts as a key role in the loss of cells by apoptosis, ferroptosis, necroptosis, pyroptosis and autophagy via mediating endoplasmic reticulum (ER) stress, oxidative stress and inflammation. This effect is bad for the normal function of organs on the one hand, on the other hand, it is benefit for anticancer activities. In this review, we will summarize the current discovery on the role and impact of TRPV4 in these programmed cell death pathological mechanisms to provide a new prospect of gene therapeutic target of related diseases.

Atrachinenins D-S, novel meroterpenoids with geranyl hydroquinone moiety from Atractylodes chinensis by the LC/MS-based molecular decoy and targeted isolation.

To mine fascinating molecules from the rhizomes of Atractylodes chinensis, the known molecular formula of atrachinenin A was used as a bait to search LC-HRMS data in different subfractions. Sixteen new meroterpenoids, atrachinenins D-S (1-16) including three unprecedented carbon skeletons (1-5) and eleven new oxygen-bridged hybrids (6-16) were obtained by the targeted isolation. Their structures and absolute configurations were elucidated by the spectroscopic data and electronic circular dichroism (ECD) calculations. The isolated compounds were evaluated for their inhibitory activity of NO production and compounds 1, 4, 8, and 13 showed moderate anti-inflammatory activity. The proposed biosynthetic pathways of 1-5 were also discussed.

Chemical Structure Diversity and Extensive Biological Functions of Specialized Metabolites in Rice.

Rice (Oryza sativa L.) is thought to have been domesticated many times independently in China and India, and many modern cultivars are available. All rice tissues are rich in specialized metabolites (SPMs). To date, a total of 181 terpenoids, 199 phenolics, 41 alkaloids, and 26 other types of compounds have been detected in rice. Some volatile sesquiterpenoids released by rice are known to attract the natural enemies of rice herbivores, and play an indirect role in defense. Momilactone, phytocassane, and oryzalic acid are the most common diterpenoids found in rice, and are found at all growth stages. Indolamides, including serotonin, tryptamine, and N-benzoylserotonin, are the main rice alkaloids. The SPMs mainly exhibit defense functions with direct roles in resisting herbivory and pathogenic infections. In addition, phenolics are also important in indirect defense, and enhance wax deposition in leaves and promote the lignification of stems. Meanwhile, rice SPMs also have allelopathic effects and are crucial in the regulation of the relationships between different plants or between plants and microorganisms. In this study, we reviewed the various structures and functions of rice SPMs. This paper will provide useful information and methodological resources to inform the improvement of rice resistance and the promotion of the rice industry.

Functionalized Fe-Doped Carbon Dots Exhibiting Dual Glutathione Consumption to Amplify Ferroptosis for Enhanced Cancer Therapy.

Nonapoptotic ferroptosis is a promising cancer treatment which offers a solution to the multidrug resistance of conventional apoptosis-induced programmed cancer cell death therapies. Reducing intracellular glutathione (GSH) is essential for inducing excess ROS and has been considered a crucial process to trigger ferroptosis. However, treatments reducing GSH alone have not produced satisfactory effects due to their restricted target. In this regard, FeCDs (Fe3+-modified l-histidine -sourced carbon dots) with dual GSH-consumption capabilities were constructed to engineer ferroptosis by self-amplifying intratumoral oxidative stress. Carbon dots have the ability to consume GSH, and the introduction of Fe3+ can amplify the GSH-consuming ability of CDs, reacting with excess H2O2 in the tumor microenvironment to generate highly oxidized •OH. This is a novel strategy through synergistic self-amplification therapy combining Fe3+ and CDs with GSH-consuming activity. The acid-triggered degradation material (FeCDs@PAE-PEG) was prepared by encapsulating FeCDs in an oil-in-water manner. Compared with other ferroptosis-triggering nanoparticles, the established FeCDs@PAE-PEG is targeted and significantly enhances the consumption efficiency of GSH and accumulation of excess iron without the involvement of infrared light and ultrasound. This synergistic strategy exhibits excellent ferroptosis-inducing ability and antitumor efficacy both in vitro and in vivo and offers great potential for clinical translation of ferroptosis.

Diversity and function of mountain and polar supraglacial DNA viruses.

Mountain and polar glaciers cover 10% of the Earth's surface and are typically extreme environments that challenge life of all forms. Viruses are abundant and active in supraglacial ecosystems and play a crucial role in controlling the supraglacial microbial communities. However, our understanding of virus ecology on glacier surfaces and their potential impacts on downstream ecosystems remains limited. Here, we present the supraglacial virus genome (SgVG) catalog, a 15-fold expanded genomic inventory of 10,840 DNA-virus species from 38 mountain and polar glaciers, spanning habitats such as snow, ice, meltwater, and cryoconite. Supraglacial DNA-viruses were highly specific compared to viruses in other ecosystems yet exhibited low public health risks. Supraglacial viral communities were primarily constrained by habitat, with cryoconite displaying the highest viral activity levels. We observed a prevalence of lytic viruses in all habitats, especially in cryoconite, but a high level of lysogenic viruses in snow and ice. Additionally, we found that supraglacial viruses could be linked to ∼83% of obtained prokaryotic phyla/classes and possessed the genetic potential to promote metabolism and increase cold adaptation, cell mobility, and phenolic carbon use of hosts in hostile environmental conditions using diverse auxiliary metabolic genes. Our results provide the first systematic characterization of the diversity, function, and public health risks evaluation of mountain and polar supraglacial DNA viruses. This understanding of glacial viruses is crucial for function assessments and ecological modeling of glacier ecosystems, especially for the Tibetan Plateau's Mountain glaciers, which support ∼20% of the human populations on Earth.

Quantitative 1H NMR with global spectral deconvolution approach for quality assessment of natural and cultured Cordyceps sinensis.

Cordyceps sinensis is a precious medicinal food which has been successfully cultivated indoors. It remains to be investigated for a simultaneous comparison on aqueous components of natural and cultivated samples. Herein, an approach of quantitative nuclear magnetic resonance (qNMR) analysis combined with global spectral deconvolution (GSD) was established for simultaneous quantification of 26 aqueous components in C. sinensis. Processed by GSD, the distorted baselines of 1H NMR spectra were greatly improved, and overlapped signals were also well separated so as to achieve accurate identification and quantitation of components in C. sinensis. Method validation by UHPLC-QTOF-MS and TOF-SIMS analysis revealed that qNMR combined with GSD is a reliable approach for simultaneous quantification of multiple components including characteristic markers of glutamine, GABA and trehalose in authentic and fake C. sinensis. The well-established qNMR approach can be used for quality assessment of natural and cultivated C. sinensis as well as differentiation from fake ones.

Sesquiterpenoids from the roots of Aucklandia costus and their anti-inflammatory activities.

Five undescribed sesquiterpenoid dimers, aucklandiolides A-E (1-5), one new sesquiterpenoid glycoside, ß-cyclocostunolide-15-ß-D-glucopyranoside (6), and seventeen known analogues (7-23) were isolated from the roots of Aucklandia costus. Their structures were elucidated by comprehensive HRESIMS and NMR spectroscopic data analysis, and their configurations were confirmed by the computational calculations of ECD and NMR chemical shifts. Aucklandiolides A and B are the first examples of dimeric sesquiterpenoids with a unique 6/6/6/5/6/6 ring system originated from a proposed Diels-Alder cycloaddition between two eudesmane sesquiterpenoids. Besides, compounds 9-11, 20, and 22 showed significant inhibition of nitric oxide production in LPS-stimulated RAW 264.7 cells at a concentration of 20 µM.

Chemical Constituents from the Fruits of Amomum kravanh and Their Role in Activating Alcohol Dehydrogenase.

Alcoholism is a worldwide health problem, and diseases caused by alcoholism are killing people every year. Amomum kravanh is a traditional Chinese medicine used to relieve hangovers. However, whether its bioactive components improve alcohol metabolism is not clear. In this study, ten new (amomumols A-J, 1-10) and thirty-five known (11-45) compounds were isolated from the fruits of Amomum kravanh by an activity-guided separation. Ten novel compounds were identified as four sesquiterpenoids (1-4), three monoterpene derivatives (5-7), two neolignans (8, 9), and a novel norsesquiterpenoid (10) with a new C14 nor-bisabolane skeleton. Their structures were determined by the comprehensive analysis of high-resolution electrospray ionization mass spectrometry (HRESIMS), nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD) calculation. The effects of all isolated compounds on the activity of alcohol dehydrogenase were evaluated in vitro, and it was found that eight compounds (11, 12, 15, 18, 26, and 36-38) exhibited significant activation effects on the alcohol dehydrogenase at 50 µM.

An integrated approach to evaluate acetamiprid-induced oxidative damage to tRNA in human cells based on oxidized nucleotide and tRNA profiling.

Acetamiprid is poisonous to mammals due to severe acetamiprid-induced oxidative stress that could cause mitochondrial dysfunctions, lipid and protein oxidation, inflammation, apoptosis, and DNA damage. Evidence has accumulated for the role of oxidative stress in changing structures and functions of transfer RNAs (tRNAs) by inducing tRNA cleavage, reprogramming tRNA modifications and impairing aminoacyl-tRNA synthetase editing sites. However, the impact of acetamiprid-induced oxidative stress on tRNA is still unknown. Here, we investigated the effects of acetamiprid on cell viability, reactive oxygen species (ROS) levels, DNA damage, cellular oxidized nucleotide concentrations, and oxidative damage to tRNA in HepG2 cells and LO2 cells. Acetamiprid can cause the significant increment of ROS and DNA oxidative damage. In this study, an integrated approach was established to simultaneously study the network of oxidized nucleotides and explore the tRNA oxidative damage after acetamiprid exposure. A simple and high-throughput liquid chromatography with tandem mass spectrometry (LC-MS/MS) method coupled with (trimethylsilyl)diazomethane (TMSD) derivatization was successfully developed to quantify 12 cellular oxidized nucleotides that cannot be detected using traditional detection methods because of the huge interferences from naturally abundant nucleotides. Meanwhile, the accumulation rate and the locating sites of 8-oxo-2, 7-dihydro-guanine (8-oxo-G) in tRNA were inspected using the established N-(tert-Butyldimethylsilyl)-N-methyl-trifluoroacetamide (MTBSTFA) labeling-based tRNA profiling method. After acetamiprid treatment, the increment of oxidized nucleoside triphosphates is smaller than that of their corresponding mono- and diphosphates, as well as the dephosphorylated nucleosides, on account of the existence of sanitization enzymes. Several tRNA fragments, CUC[m1A]Gp, CACGp, [Cm]C[m2G]p, and DDGp, are significantly downregulated in acetamiprid-treated HepG2 cells, while only [Cm]C[m2G]p in acetamiprid-treated LO2 cells. According to the profiling results, the significantly changed fragment CUC[m1A]Gp might be caused by the oxidation of guanine (G) to form 8-oxo-G at position 15 in human tRNAphe([Gm]AA), providing more information about the effect of oxidized nucleobases on tRNA's functions.

A Multiple Stimuli-Responsive NanoCRISPR Overcomes Tumor Redox Heterogeneity to Augment Photodynamic Therapy.

Redox heterogeneity of tumor cells has become one of the key factors leading to the failure of conventional photodynamic therapy (PDT). Exploration of a distinctive therapeutic strategy addressing heterogeneous predicaments is an appealing yet highly challenging task. Herein, a multiple stimuli-responsive nanoCRISPR (Must-nano) with spatial arrangement peculiarities in nanostructure and intracellular delivery is fabricated to overcome redox heterogeneity at both genetic and phenotypic levels for tumor-specific activatable PDT. Must-nano consists of a redox-sensitive core loading CRISPR/Cas9 targeting hypoxia-inducible factors-1α (HIF-1α) and a rationally designed multiple-responsive shell anchored by chlorin e6 (Ce6). Benefiting from the perfect coordination of structure and function, Must-nano avoids enzyme/photodegradation of the CRISPR/Cas9 system and exerts prolonged circulation, precise tumor recognition, and cascade-responsive performances to surmount tumor extra/intracellular barriers. After internalization into tumor cells, Must-nano could undergo hyaluronidase-triggered self-disassembly with charge reversal and rapid endosomal escape, followed by site-specific release and spatially asynchronous delivery of Ce6 and CRISPR/Cas9 under stimulations of redox signals, which not only improves tumor vulnerability to oxidative stress by complete HIF-1α disruption but also destroys the intrinsic antioxidant mechanism through glutathione depletion, thereby homogenizing redox-heterogeneous cells into oxidative stress-sensitive cell subsets. Under laser irradiation, Must-nano eventually exhibits optimal potency to amplify oxidative damage, effectively inhibiting the growth and hypoxia survival of redox-heterogeneous tumor in vitro and in vivo. Overall, our redox homogenization tactic significantly maximizes PDT efficacy and offers a promising strategy to overcome tumor redox heterogeneity in the development of antitumor therapies.

Di- and Triterpenoids from the Rhizomes of Isodon amethystoides and Their Anti-inflammatory Activities.

Amethystoidesic acid (1), a triterpenoid with an unprecedented 5/6/6/6 tetracyclic skeleton, and six undescribed diterpenoids, amethystoidins A-F (2-7), were isolated from the rhizomes of Isodon amethystoides along with 31 known di- and triterpenoids (8-38). Their structures were fully elucidated via extensive spectroscopic analysis including 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HRESIMS), and electronic circular dichroism (ECD) calculations. Compound 1 is the first example of a triterpenoid possessing a rare ring system (5/6/6/6) derived from a contracted A-ring and the 18,19-seco-E-ring of ursolic acid. Compounds 6, 16, 21, 22, 24, and 27 significantly inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, which could be partly mediated by the downregulation of LPS-induced inducible nitric oxide synthase (iNOS) protein expression.

Uterine choriocarcinoma coexistence with endometroid adenocacinoma: a case report and literature review.

BACKGROUND: Choriocarcinoma coexisting with endometrial carcinoma is rare. To the best of our knowledge, only one case of choriocarcinoma coexisting with endometrial carcinoma has been reported. CASE PRESENTATION: Here, we present this case and provide a literature review. A 38-year-old unmarried nulliparous woman presented to the clinic with a menstrual disorder for more than 3 months. She then underwent a hysteroscopic procedure. The pathological findings were malignant, two types of carcinoma, and no transitional lesions were observed; about 85% of them were choriocarcinoma with smooth muscle infiltration and intravascular investigation of the thrombus; about 15% were highly differentiated endometrioid adenocarcinoma; Immunohistochemistry (endometrioid/choriocarcinoma): Vim (+ + / + + +), P40 (+ ±), CK5/6 multifocal ( ±), CK7 ( ±), EMA (+ ±), P16 multifocal ( ±), P53 (+ / + +), WT-1 (-/ + +), hCG (-/ + + +), CD138 (-/ + + +), Gly-3 (-/-), ER ( ±), PR (+ ±), Sall-4 (-/-), P21 (-/ +), P27 (-/ + + +), CyclinE (-/ + +), Ki67 positivity rate (10%/95%). We performed a laparoscopic hysterectomy, bilateral adnexectomy, and pelvic and para-abdominal lymph node dissection after five cycles of chemotherapy. She was diagnosed with choriocarcinoma with endometrial cancer, stage IVb choriocarcinoma and stage IA endometrial cancer. Postoperative radiochemotherapy was administered. The patient was disease-free 40 months after the treatment ended. CONCLUSION: We report a case of choriocarcinoma coexisting with endometrial carcinoma and provide a literature review that may help inspire additional studies in the future.

Oridonin inhibits inflammation of epithelial cells via dual-targeting of CD31 Keap1 to ameliorate acute lung injury.

Introdcution: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are major causes of COVID-19 mortality. However, drug delivery to lung tissues is impeded by endothelial cell barriers, limiting the efficacy of existing treatments. A prompt and aggressive treatment strategy is therefore necessary. Methods: We assessed the ability of anti-CD31-ORI-NPs to penetrate endothelial cell barriers and specifically accumulate in lung tissues using an animal model. We also compared the efficacy of anti-CD31-ORI-NPs to that of free oridonin in ameliorating acute lung injury and evaluated the cytotoxicity of both treatments on endothelial cells. Results: Compared to free ORI, the amount of anti-CD31-ORI-NPs accumulated in lung tissues increase at least three times. Accordingly, anti-CD31-ORI-NPs improve the efficacy three times on suppressing IL-6 and TNF-a secretion, ROS production, eventually ameliorating acute lung injury in animal model. Importantly, anti-CD31-ORI-NPs significantly decrease the cytotoxicity at least two times than free oridonin on endothelial cells. Discussion: Our results from this study will not only offer a novel therapeutic strategy with high efficacy and low toxicity, but also provide the rational design of nanomaterials of a potential drug for acute lung injury therapy.