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Foxtail millet (Setaria italica (L.) P. Beauv.) is an environmentally friendly crop that meets the current requirements of international food security and is widely accepted as a photosynthesis research model. However, whether exogenous sucrose treatment has a positive effect on foxtail millet growth remains unknown. Here, we employed physiological and molecular approaches to identify photosynthesis and source capacity associated with exogenous sucrose during the growth of Jingu 21 seedlings. RNA-seq analysis showed that some differentially expressed genes (DEGs) related to photosynthesis and carotenoid biosynthesis were induced by exogenous sucrose and that most of these genes were up-regulated. An increase in gas exchange parameters, chlorophyll content, and chlorophyll fluorescence of Jingu 21 was noted after exogenous sucrose addition. Furthermore, exogenous sucrose up-regulated genes encoding sucrose and hexose transporters and enhanced starch and sucrose metabolism. More DEGs were up-regulated by sucrose, the nonstructural carbohydrate (NSC) content in the leaves increased and energy metabolism and sucrose loading subsequently improved, ultimately enhancing photosynthesis under normal and dark conditions. Further analysis revealed that WRKYs, ERFs, HY5, RAP2, and ABI5 could be key transcription factors involved in growth regulation. These results indicate that exogenous sucrose affects the normal photosynthetic performance of foxtail millet by increasing NSC transport and loading. They improve our understanding of the molecular mechanisms of the effects of exogenous sucrose on photosynthesis in foxtail millet, providing an effective measure to enhance source-sink relationships and improve yield.
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Although it is an effective treatment for acute myeloid leukemia (AML), chemotherapy leads to myelosuppression and poor hematopoietic reconstruction. Hematopoiesis is regulated by bone marrow (BM) endothelial cells (ECs), and BM ECs are dysfunctional in acute leukemia patients with poor hematopoietic reconstitution after allogenic hematopoietic stem cell transplantation. Thus, it is crucial to explore the underlying mechanism of EC impairment and establish strategies for targeted therapy. TGF-ß signaling was found to be upregulated in ECs from AML patients in complete remission (CR ECs) and led to CR EC damage. Administration of a TGF-ß inhibitor rescued the dysfunction of ECs caused by TGF-ß1 expression in vitro, especially their hematopoiesis-supporting ability. Moreover, inhibition of TGF-ß expression repaired the BM EC damage triggered by chemotherapy in both AML patients in vitro and in an AML-CR murine model, and restored normal hematopoiesis without promoting AML progression. Mechanistically, our data reveal alterations in the transcriptomic pattern of damaged BM ECs, accompanied by the overexpression of downstream molecules TGF-ßR1, pSmad2/3, and functional genes related to adhesion, angiogenesis suppression and pro-apoptosis. Collectively, our findings reveal for the first time that the activation of TGF-ß signaling leads to BM EC dysfunction and poor hematopoietic reconstitution. Targeting TGF-ß represents a potential therapeutic strategy to promote multilineage hematopoiesis, thereby benefiting more cancer patients who suffer from myelosuppression after chemotherapy.
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BACKGROUND: Evidence regarding the association between malnutrition risk and the prognosis of geriatric heart failure (HF) patients undergoing left ventricular assist device (LVAD) implantation is lacking. Our study aims to investigate how malnutrition risk, assessed using the geriatric nutritional risk index (GNRI) values, relates to the outcomes of geriatric HF patients undergoing LVAD, using data from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registry. METHODS: A retrospective analysis was conducted using data from INTERMACS registry. Patients aged 65 and above who received LVAD implantation between 2008 and 2017 were included. The GNRI was used to stratify patients into three groups: absence of risk (GNRI > 98), mild risk (GNRI 92-98), and moderate to severe risk (GNRI < 92). The primary outcome was long-term survival for up to four years following LVAD implantation. RESULTS: We included 5429 patients aged 65 and above undergoing LVADs. The malnutrition risk was presented in 75.8% of the patients before implantation, decreasing to 32.4% at 3 months, and 59.5% at 24 months post-implantation. Moderate-to-severe malnutrition risk, both pre-implant and 6 months post-implant, was associated with an increased risk of death (pre-implant: hazard ratio (HR): 1.25 [95% CI: 1.12-1.40], p < 0.001; 6 months: HR: 2.36 [95% CI: 2.01-2.77], p < 0.001). Mortality decreased with increasing pre-implant GNRI up to approximately 100 and 6-month post-implant GNRI up to 104. Patients with malnutrition risk also had an increased risk of infection, poor quality of life (QoL), and reduced functional exercise capacity after the LVAD implantation. CONCLUSIONS: Malnutrition risk was highly prevalent in HF patients aged 65 and above undergoing LVADs implantation. The presence of malnutrition risk was associated with an increased risk of death, infection, poor quality of life, and reduced functional exercise capacity.
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This study aimed to evaluated the effect of dietary fermented pineapple residue (FPR) on the chemical composition, antioxidant capacity, meat quality, fatty acid profile, and volatile compounds in yellow-feathered chickens. GC-IMS technique combined with multivariate analysis were performed to clarify the key volatile compounds. The results showed that dietary FPR improved meat quality by increasing the antioxidant capacity and pH value and decreasing cooking loss of breast muscle. The fatty acid profile was altered in breast muscle of chickens that fed with FPR. GC-IMS detected 43 volatile compounds in breast muscle, including mainly aldehydes, alcohols, esters, and ketones. Among them, 12 volatile compounds could serve as potential aroma markers to distinguish meat flavor of chickens fed with FPR. Correlation analysis revealed that C18:1n9c, C18:2n6, and PUFA are important contributors for meat flavor formation. In conclusion, dietary FPR improved antioxidant capacity, meat quality, fatty acid profile, and volatile compounds of breast muscle in chickens.
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Microplastics have emerged as a pervasive pollutant across various environmental media. Nevertheless, our understanding of their occurrence, sources, and drivers in global lakes still needs to be completed due to limited data. This study compiled data from 117 studies (2016-May 2024) on microplastic contamination in lake surface water and sediment, encompassing surface water samples in 351 lakes and lake sediment samples in 200 lakes across 43 countries. Using meta-analysis and statistical methods, the study reveals significant regional variability in microplastic pollution, with concentrations ranging from 0.09 to 207,500 items/m3 in surface water and from 5.41 to 18,100 items/kg in sediment. Most microplastics were under 1 mm in particle size, accounting for approximately 79 % of lake surface water and 76 % of sediment. Transparent and blue microplastics were the most common, constituting 34 % and 21 % of lake surface water and 28 % and 18 % of sediment, respectively. Fibers were the dominant shape, representing 47 % of lake surface water and 48 % of sediment. The primary identified polymer types were polyethylene (PE), polypropylene (PP), and polyethylene terephthalate (PET). Countries like India, Pakistan, and China had higher contamination levels. Positive correlations were found between microplastic abundance in surface water and factors like human footprint index (r = 0.29, p < 0.01), precipitation (r = 0.21, p < 0.05), and net surface solar radiation (r = 0.43, p < 0.001). In contrast, negative correlations were observed with the human development index (r = -0.61, p < 0.01) and wind speed (r = -0.42, p < 0.001). In sediment, microplastics abundance correlated positively with the human footprint index (r = 0.45, p < 0.001). This study underscores the variability in microplastic pollution in global lakes and the role of human activities and environmental factors, offering a valuable reference for future research.
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PURPOSE: To determine the relationship between HLA-B gene mutations and levofloxacin-induced toxic epidermal necrolysis (TEN). METHODS: A 71-year-old Chinese woman developed TEN after oral administration of solifenacin (5 mg) and levofloxacin (0.5 g) for cystitis. HLA-B*5801 and HLA-B*1502 alleles were detected using real-time PCR. FINDINGS: After supportive therapy (antiallergic treatments, plasma exchange, etc) and withdrawal of the culprit medication levofloxacin, the patient was discharged with re-epithelialization of the exfoliated skin. The patient was HLA-B*1502 allele positive and HLA-B*5801 allele negative. IMPLICATIONS: This is the first report of levofloxacin-induced TEN suspected to be caused by mutations in the HLA-B*1502 allele.
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The glomerular basement membrane (GBM) is a critical component of the glomerular filtration barrier (GFB), with its thickness directly influencing renal function. While a uniformly thinned GBM can cause hematuria while preserving normal renal function, this condition is typically diagnosed as thin basement membrane nephropathy (TBMN). However, the pathogenesis and potential progression to renal insufficiency of TBMN are not fully understood. In this study, we analyzed clinical cohorts presenting with microscopic hematuria who underwent genetic testing and identified five novel pathogenic FN1 mutations. Through bioinformatics analysis of these variants, expression localization analysis of GBM-related molecules in renal biopsies, and functional studies of the mutants, we found that these variants exhibited gain-of-function characteristics. This led to the excessive deposition of aberrant serum-derived FN1 variants on glomerular endothelial cells rather than cell-type-specific variants. The deposition competitively binds FN1 variants to Integrin ß1, disrupting the interaction with Laminin α5ß2γ1 and subsequently reducing the expression of key GBM components, resulting in TBMN. This study elucidated, for the first time, the genetic pathogenesis of TBMN caused by FN1 variants. It provides a crucial foundation for understanding the progression of renal dysfunction associated with simple hematuria, highlights the potential for targeted therapeutic strategies, and differentiates TBMN from early-stage Alport syndrome.
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BACKGROUND: Immune checkpoint blockade (ICB) has been improving the patient outcome in multiple cancer types. However, not all patients respond to ICB. Biomarkers are needed for selecting appropriate patients to receive ICB. CD74 is an important chaperone that regulates antigen presentation for immune response. However, the relationship between CD74 expression and ICB response remains elusive. METHODS: The unified normalized pan-cancer dataset was downloaded from the UCSC database. Wilcoxon Rank Sum Rank Tests were used to analyze the expression differences between normal and tumor samples in each tumor type. Then, the prognostic value of CD74 was determined using univariable Cox proportional hazards regression analysis. The STRING database was utilized to construct the protein-protein interaction (PPI) network of CD74 and the signal pathways were analyzed as well. The correlation of CD74 expression with immune cells and immune regulating genes was investigated in the TIMER database. The TIDE framework was utilized to evaluate the relationship between CD74 expression and the response to immunotherapy. Moreover, the localization of CD74 in the tumor immune microenvironment was verified using multiplex immunohistochemistry. Clinically annotated samples from 38 patients with esophageal cancer treated with neoadjuvant chemotherapy combined with ICB were analyzed for CD74 expression using immunohistochemistry. RESULTS: In this study, we investigated the prognostic and predictive value of CD74 in different types of cancer. Compared with normal tissue, the expression of CD74 was higher in tumor tissue in various cancers. High expression of CD74 was associated with improved patient prognosis in the majority of cancers. CD74 and its interacting proteins were mainly enriched in the immune-related pathways. The expression of CD74 was significantly positively correlated with B cells, CD4 T-cells, CD8 T-cells, neutrophils, macrophages and dendritic cells. TIDE analysis showed that tumors with high CD74 expression may have better responses to immunotherapy and improved patient survival. In patients with esophageal cancer who had received ICB, higher intratumoral CD74 expression was associated with improved response to ICB. CONCLUSIONS: The findings of this study suggest that the high expression of CD74 may be a potential predictive biomarker of response to ICB.
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With the rapid development in sensor network technology, the complexity and diversity of application scenarios have put forward more and more new requirements for inductor-capacitor (LC) sensors, for instance, multi-parameter simultaneous monitoring. Here, the parity-time (PT) symmetry concept in quantum mechanics is applied to LC passive wireless sensing. Two or even three parameters can be monitored simultaneously by observing the frequency response of the reflection coefficient at the end of the readout circuit. In particular, for three-parameter detection, a novel detection method is studied to extract the three resonant frequencies of the system through the phase-frequency characteristics of the reflection coefficient, which has never appeared in the previous literature on PT symmetry. The changes in three resonant frequencies are in response to changes in the three parameters in the environment. We show theoretically and demonstrate experimentally that the PT-symmetric LC sensor can realize multi-parameter measurement using a series LCR circuit as the sensor and a symmetric adjustable LCR circuit as the readout circuit. Our work paves the way for applying PT symmetry in multi-parameter detection.
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The risk of adverse effects in Electroconvulsive Therapy (ECT), such as cognitive impairment, can be high if an excessive stimulus is applied to induce the necessary generalized seizure (GS); Conversely, inadequate stimulus results in failure. Recent efforts to automate this task can facilitate statistical analyses on individual parameters or qualitative predictions. However, this automation still significantly lags behind the requirements in clinical practices. This study addresses this issue by predicting the probability of GS induction under the joint restriction of a patient's EEG (electroencephalogram) and the stimulus parameters, sustained by a two-stage learning model (namely ECTnet): 1) Temporal-Spatial Feature Learning. Channel-wise convolution via multiple convolution kernels first learns the deep features of the EEG, followed by a "ConvLSTM" constructing the temporal-spatial features aided with the enforced convolution operations at the LSTM gates; 2) GS Prediction. The probability of seizure induction is predicted based on the EEG features fused with stimulus parameters, through which the optimal parameter setting(s) may be obtained by minimizing the stimulus charge while ensuring the probability above a threshold. Experiments have been conducted on EEG data from 96 subjects with mental disorders to examine the performance and design of ECTnet. These experiments indicate that ECTnet can effectively automate the selection of optimal stimulus parameters: 1) an AUC of 0.746, F1-score of 0.90, a precision of 89% and a recall of 93% in the prediction of seizure induction have been achieved, outperforming the state-of-the-art counterpart, and 2) inclusion of parameter features increases the F1-score by 0.054.
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Despite the skin microbiome has been linked to skin health and diseases, its role in modulating human skin appearance remains understudied. Using a total of 1244 face imaging phenomes and 246 cheek metagenomes, we first established three skin age indices by machine learning, including skin phenotype age (SPA), skin microbiota age (SMA), and skin integration age (SIA) as surrogates of phenotypic aging, microbial aging, and their combination, respectively. Moreover, we found that besides aging and gender as intrinsic factors, skin microbiome might also play a role in shaping skin imaging phenotypes (SIPs). Skin taxonomic and functional α diversity was positively linked to melanin, pore, pigment, and ultraviolet spot levels, but negatively linked to sebum, lightening, and porphyrin levels. Furthermore, certain species were correlated with specific SIPs, such as sebum and lightening levels negatively correlated with Corynebacterium matruchotii, Staphylococcus capitis, and Streptococcus sanguinis. Notably, we demonstrated skin microbial potential in predicting SIPs, among which the lightening level presented the least error of 1.8%. Lastly, we provided a reservoir of potential mechanisms through which skin microbiome adjusted the SIPs, including the modulation of pore, wrinkle, and sebum levels by cobalamin and heme synthesis pathways, predominantly driven by Cutibacterium acnes. This pioneering study unveils the paradigm for the hidden links between skin microbiome and skin imaging phenome, providing novel insights into how skin microbiome shapes skin appearance and its healthy aging.
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Microbiota , Fenótipo , Envelhecimento da Pele , Pele , Humanos , Pele/microbiologia , Pele/metabolismo , Pele/diagnóstico por imagem , Microbiota/genética , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , MetagenomaRESUMO
Background: Fluoroquinolones are broad-spectrum antibiotics with significant antimicrobial activity. Despite their therapeutic benefits, they are associated with a range of adverse drug reactions (ADRs), particularly those affecting the central nervous system (CNS). This study aimed to analyze the psychiatric ADRs linked to fluoroquinolones using data from the FDA Adverse Event Reporting System (FAERS) database. Methods: A retrospective pharmacovigilance study was conducted using FAERS data from Q1 2004 to Q4 2023. The data processing phase involved the FDA-recommended deduplication method, and ADRs were classified according to Medical Dictionary for Regulatory Activities (MedDRA). Disproportionality analysis was performed using the reporting odds ratio (ROR), and statistical significance was assessed using the Chi-square test or Fisher's exact test. Results: The study identified 84,777 reports associated with fluoroquinolones, with 359,480 Preferred Terms-annotated entries, 27,816 of these reports were psychiatric ADRs. Mood disorders were the most frequently reported, including anxiety, depression, and delirium, with some reports escalating to suicidal ideation and behaviors. The Standardized MedDRA Query classification system was used to categorize these ADRs into Depression, Suicide/self-injury, Psychosis and psychotic disorders, and Non-infectious encephalopathy/delirium. Ciprofloxacin was most frequently linked to depression and suicidal ideation, while moxifloxacin showed a robust correlation with delirium. The risk of psychiatric ADRs varied by age group, with affective disorders more prevalent in adults under 65 and psychosis and delirium in those over 65. Conclusion: Fluoroquinolones are associated with a range of psychiatric ADRs, with notable differences between the drugs in the class. The study highlights the need for caution in prescribing fluoroquinolones, particularly for patients with pre-existing mental health conditions or those in higher risk age groups. The findings also underscore the importance of considering age-specific preventive strategies when administering these antibiotics.
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BACKGROUND: The mismatch of medical resources is a significant issue in global healthcare, undermining both service accessibility and system efficiency. In China, despite the implementation of the "Healthy China" strategy, persistent mismatches remain due to factors such as industrialization, urbanization, and population aging. This study empirically evaluates the impact of Public Hospital Reform (PHR) on mitigating these mismatches. METHODS: A Difference-in-Differences (DD) approach is applied to panel data from 300 cities spanning 2010 to 2021, using the phased implementation of PHR as a quasi-natural experiment. This allows for a comparative analysis of changes in resource allocation between cities that adopted the reform and those that did not. Quantile regression assesses the effects of PHR across varying levels of resource mismatch, while mechanism tests investigate how PHR influences mismatches through cost reduction and supply expansion. RESULTS: PHR is found to reduce medical resource mismatches by 13.9%, primarily driven by cost reductions and increased resource supply. The effects are more pronounced at both lower and higher levels of mismatch, with a limited impact at mid-levels. Furthermore, the reform's effectiveness diminishes as it is extended to more cities, suggesting a potential saturation effect. CONCLUSIONS: This study demonstrates that PHR significantly alleviates medical resource mismatches in China. The findings underscore the need to focus on cost control and resource supply in future healthcare reforms, providing key insights for policymakers in developing countries facing similar healthcare resource challenges.
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PURPOSE: To evaluate the effect of bone nail and artificial periosteum combined with iliac cancellous bone grafting in repairing cleft lip and palate with alveolar cleft during dental replacement. METHODS: The clinical data of 82 children with cleft lip and palate with alveolar cleft during dental replacement period were retrospectively analyzed from January 2020 to December 2023, and were divided into control group (iliac cancellous bone grafting alone, n=42) and experimental group (combined iliac cancellous bone grafting with bone nail and artificial periosteum, n=40) according to the operation method. The viable bone volume in bone graft area, absorption rate of whole bone graft and different bone graft areas, success rate of bone graft, survival rate of bone graft and complications were compared between the two groups. SPSS 25.0 software package was used for statistical analysis. RESULTS: The surviving bone volume in the bone graft area was significantly larger in the experimental group 3 and 9 months after operation(Pï¼0.05). There was no significant difference in viable bone volume in bone graft area between the two groups 9 months and 3 months after surgery (Pï¼0.05). The bone graft absorptivity of the experimental group was significantly lower than that of the control group 3, 9 months and 3-9 months after surgery(Pï¼0.05), and there was no significant difference between the two groups at 3, 9 months after surgery(Pï¼0.05). The absorption rate of bone graft in 1/2 area of nasal cavity, 1/2 area of alveolar ridge, 1/2 area of lip and 1/2 area of palate in the experimental group was significantly lower than that in the control group 3 and 9 months after operation(Pï¼0.05). The absorptivity of bone graft in 1/2 area of alveolar ridge was significantly higher than that in 1/2 area of nasal cavity, and the absorptivity of bone graft in 1/2 area of palatal side was significantly higher than that in 1/2 area of lip in both groups (Pï¼0.05). The success rate and survival rate of bone grafting in the experimental group were significantly higher than those in the control group(Pï¼0.05). The complication rate of the experimental group was significantly lower than that of the control group (Pï¼0.05). CONCLUSIONS: Bone nail and artificial periosteum combined with iliac cancellous bone graft can effectively repair cleft lip and palate with alveolar cleft during dental replacement, reduce bone absorption rate and complications, and improve bone formation effect. Meanwhile, postoperative bone mass absorption mainly occurs within 3 months after surgery, and mainly occurs in the alveolar crest area and palatine area.
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Pinos Ortopédicos , Transplante Ósseo , Fenda Labial , Fissura Palatina , Ílio , Periósteo , Humanos , Fissura Palatina/cirurgia , Fenda Labial/cirurgia , Periósteo/transplante , Estudos Retrospectivos , Ílio/transplante , Transplante Ósseo/métodos , Osso Esponjoso/transplante , CriançaRESUMO
With the current unmet demand for effective pain relief, analgesics without major central adverse effects are highly appealing, such as peripherally restricted kappa-opioid receptor (KOR) agonists. In this study, Conorphin-66, an analog of the selective KOR peptide agonist Conorphin T, was pharmacologically characterized in a series of experiments, with CR845 serving as the reference compound. Firstly, in vitro functional assay indicated that Conorphin-66 selectively activates KOR and exhibits weak ß-arrestin2 signaling bias (-1.54 versus -4.35 for CR845). Additionally, subcutaneous Conorphin-66 produced potent antinociception in mouse pain models with ED50 values ranged from 0.02 to 3.28 µmol/kg, including tail-flick test, post-operative pain, formalin pain, and acetic acid-induced visceral pain. Similarly, CR845 exert potent antinociception in mouse pain models ranged from 0.15 to 1.47 µmol/kg. Notably, antagonism studies revealed that the analgesic effects of Conorphin-66 were mainly mediated by the peripheral KOR. Furthermore, Conorphin-66 produced non-tolerance-forming antinociception over 8 days. Unlike CR845, subcutaneous Conorphin-66 did not promote the sedation, anxiogenic effects, depressive-like effects, but did exhibit diuretic activity. Further study showed that Conorphin-66 does not have apparent antipruritic effects in an acute itch model. Overall, Conorphin-66 emerges as a novel peripherally restricted KOR agonist that produced potent antinociception with reduced side effects.
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Receptores Opioides kappa , Animais , Receptores Opioides kappa/agonistas , Receptores Opioides kappa/metabolismo , Camundongos , Masculino , Humanos , Analgésicos/farmacologia , Relação Dose-Resposta a Droga , Dor/tratamento farmacológico , Dor/metabolismo , Células HEK293RESUMO
A smart window that dynamically regulates light transmittance is crucial for modern life end-users and promising for on-demand optical devices. The advent of three-dimensional (3D) photonic crystal microspheres has enriched the functions of a smart window. However, the smart window formed by polymer microspheres encounters poor mechanical strength and microstructural defects. Herein, to solve this limitation, we report the microsphere-based smart window composed of tightly packed cross-linked polymer microspheres (as a precursor) containing organic photochromic dyes, followed by compression under a high elastic state. When excited under an ultraviolet supply, our smart window showed a rapid and reversible fluorescent photoluminescence without fatigue (50 cycles). Moreover, the bulk devices with a microsphere cross-linked network structure enable excellent mechanical strength (hardness reached 0.158 GPa) and visible-light transparency. Interestingly, a QR code can be recognized under visible light exposure but not under ultraviolet light exposure because of photoluminescence of the smart window. Our method generally provided a paradigm for various amorphous polymers, which can be regarded as a simple and effective approach to build a versatile strategy to introduce an ideal marketplace with economic and community benefits.
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The ecological construction in coastal saline-alkali areas urgently needs to be explored in terms of water-salt regulation management and functional irrigation. In this paper, the extremely severe saline soil in the eastern coastal area of the North China Plain was selected for vegetation rehabilitation by drip irrigation. Through two-year field experiments, the spatial and temporal soil salinity-water dynamics of three land use types (LUTS) under two irrigation strategies (IIS) were systematically studied. The results revealed: (1) The soils in the understory grassland and shrub land root zones remained stable for desalination, with the average ECe decreasing to 0.69 dS/m and 0.71 dS/m under autumn irrigation at surface, and 0.66 dS/m and 0.85 dS/m under winter irrigation. And a slight salt accumulation occurred in the bare land in stage IV. (2)The soil surface moisture increased, and the bulk density decreased significantly with drip irrigation. The final moisture of understory grassland and shrub land was 3.85 and 2.97 times that of the bare land layer at 0-10 cm, 2.55 and 1.97 times at 10-20 cm, and 1.61 times and 1.47 times at 20-40 cm, respectively. (3)Due to quick salt rinsing, Salix matsudana and Hibiscus maintained a high survival rate, and the germination of understory vegetation further increased the vegetation coverage. Meanwhile perennial understory herbs gradually became the dominant species, which positively effects on the maintenance of soil low-salt environment. (4)There were significant differences in SWC and ECe between autumn and winter irrigation treatment during stage I and stage II, indicating that irrigation strategies only impact on soil water-salt movement in the early stage. While there was no significant difference between understory grassland and shrub land, indicating that the research about the effects of vegetation cover type on water-salt transport should take a longer time scale.
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The approved traditional Asian medicine RTA408 (Omaveloxolone) has demonstrated potent anti-inflammatory properties in the treatment of Friedreich's ataxia. However, its effect on lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains poorly understood. This study aims to evaluate the effect of RTA408 on LPS-induced ALI and elucidate its underlying mechanisms. In this study, in vivo experiments demonstrated that RTA408 significantly ameliorated LPS-induced mouse ALI, characterized by reduced pathological damage and neutrophil infiltration as well as decreased lung edema of murine lung tissues. Moreover, LPS administration induced ferroptosis in ALI mice, evidenced by increased MDA levels, reduced GSH and SOD activity, and decreased expression of ferroptosis repressors (GPX4 and SLC7A11), whereas RTA408 reversed these changes. Consistently, RTA408 reduced ferroptosis and improved cell damage in LPS-stimulated MLE-12 cells, as evidenced by decreased ROS and MDA levels, increased SOD, GSH activity and ferroptosis repressors expression. Meanwhile, the protective effective of RTA408 on LPS-induced oxidative damage was blocked by ferroptosis inhibitor ferrostatin-1 (Fer-1). Mechanistic studies demonstrated that RTA408 inhibited the expression and nuclear translocation of Bach1, and the anti-ferroptosis effect was diminished by Bach1 siRNA or Bach1 knockout (Bach1-/-) mice. Furthermore, Bach1-/- mice exhibited attenuated ALI induced by LPS compared to wild-type (WT) mice, and the protective effect of RTA408 on LPS-challenged ALI was not observed in Bach1-/- mice. In conclusion, our data suggested that RTA408 alleviates LPS-induced ALI by interfering Bach1-mediated ferroptosis and might be a novel candidate for LPS-induced ALI/ARDS therapy.