CircRNA and lncRNA-encoded peptide in diseases, an update review.

Non-coding RNAs (ncRNAs), including circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs), are unique RNA molecules widely identified in the eukaryotic genome. Their dysregulation has been discovered and played key roles in the pathogenesis of numerous diseases, including various cancers. Previously considered devoid of protein-coding ability, recent research has revealed that a small number of open reading frames (ORFs) within these ncRNAs endow them with the potential for protein coding. These ncRNAs-derived peptides or proteins have been proven to regulate various physiological and pathological processes through diverse mechanisms. Their emerging roles in disease diagnosis and targeted therapy underscore their potential utility in clinical settings. This comprehensive review aims to provide a systematic overview of proteins or peptides encoded by lncRNAs and circRNAs, elucidate their production and functional mechanisms, and explore their promising applications in cancer diagnosis, disease prediction, and targeted therapy.

Recent advances of m6A methylation in skeletal system disease.

Skeletal system disease (SSD) is defined as a class of chronic disorders of skeletal system with poor prognosis and causes heavy economic burden. m6A, methylation at the N6 position of adenosine in RNA, is a reversible and dynamic modification in posttranscriptional mRNA. Evidences suggest that m6A modifications play a crucial role in regulating biological processes of all kinds of diseases, such as malignancy. Recently studies have revealed that as the most abundant epigentic modification, m6A is involved in the progression of SSD. However, the function of m6A modification in SSD is not fully illustrated. Therefore, make clear the relationship between m6A modification and SSD pathogenesis might provide novel sights for prevention and targeted treatment of SSD. This article will summarize the recent advances of m6A regulation in the biological processes of SSD, including osteoporosis, osteosarcoma, rheumatoid arthritis and osteoarthritis, and discuss the potential clinical value, research challenge and future prospect of m6A modification in SSD.

The role of AMPK in macrophage metabolism, function and polarisation.

AMP-activated protein kinase (AMPK) is a ubiquitous sensor of energy and nutritional status in eukaryotic cells. It plays a key role in regulating cellular energy homeostasis and multiple aspects of cell metabolism. During macrophage polarisation, AMPK not only guides the metabolic programming of macrophages, but also counter-regulates the inflammatory function of macrophages and promotes their polarisation toward the anti-inflammatory phenotype. AMPK is located at the intersection of macrophage metabolism and inflammation. The metabolic characteristics of macrophages are closely related to immune-related diseases, infectious diseases, cancer progression and immunotherapy. This review discusses the structure of AMPK and its role in the metabolism, function and polarisation of macrophages. In addition, it summarises the important role of the AMPK pathway and AMPK activators in the development of macrophage-related diseases.

Recent advances of exosomal circRNAs in cancer and their potential clinical applications.

Circular RNA (circRNA) is a type of non-coding RNA that forms a covalently closed, uninterrupted loop. The expression of circRNA differs among cell types and tissues, and various circRNAs are aberrantly expressed in a variety of diseases, including cancer. Aberrantly expressed circRNAs contribute to disease progression by acting as microRNA sponges, functional protein sponges, or novel templates for protein translation. Recent studies have shown that circRNAs are enriched in exosomes. Exosomes are spherical bilayer vesicles released by cells into extracellular spaces that mediate intercellular communication by delivering cargoes. These cargoes include metabolites, proteins, lipids, and RNA molecules. Exosome-mediated cell-cell or cell-microenvironment communications influence the progression of carcinogenesis by regulating cell proliferation, angiogenesis, metastasis as well as immune escape. In this review, we summarize the current knowledge about exosomal circRNAs in cancers and discuss their specific functions in tumorigenesis. Additionally, we discuss the potential value of exosomal circRNAs as diagnostic biomarkers and the potential applications of exosomal circRNA-based cancer therapy.

Circular RNAs in chemotherapy resistance of lung cancer and their potential therapeutic application.

Lung cancer is one of the high malignancy-related incidence and mortality worldwide, accounting for about 13% of total cancer diagnoses. Currently, the use of anti-cancer agents is still the main therapeutic method for lung cancer. However, cancer cells will gradually show resistance to these drugs with the progress of treatment. And the molecular mechanisms underlying chemotherapy agents resistance remain unclear. circRNAs are newly identified noncoding RNAs molecules with covalently closed circular structures. Previous studies have shown that circRNAs are associated with tumorigenesis and progression of various cancers, including lung cancer. Recently, growing reports have suggested that circRNAs could contribute to drug resistance of lung cancer cell through different mechanisms. Therefore, in this review, we summarized the functions and underlying mechanisms of circRNAs in regulating chemoresistance of lung cancer and discussed their potential applications for diagnosis, prognosis, and treatment of lung cancer.

Superior Selective CO2 Adsorption and Separation over N2 and CH4 of Porous Carbon Nitride Nanosheets: Insights from GCMC and DFT Simulations.

Development of high-performance materials for the capture and separation of CO2 from the gas mixture is significant to alleviate carbon emission and mitigate the greenhouse effect. In this work, a novel structure of C9N7 slit was developed to explore its CO2 adsorption capacity and selectivity using Grand Canonical Monte Carlo (GCMC) and Density Functional Theory (DFT) calculations. Among varying slit widths, C9N7 with the slit width of 0.7 nm exhibited remarkable CO2 uptake with superior CO2/N2 and CO2/CH4 selectivity. At 1 bar and 298 K, a maximum CO2 adsorption capacity can be obtained as high as 7.06 mmol/g, and the selectivity of CO2/N2 and CO2/CH4 was 41.43 and 18.67, respectively. In the presence of H2O, the CO2 uptake of C9N7 slit decreased slightly as the water content increased, showing better water tolerance. Furthermore, the underlying mechanism of highly selective CO2 adsorption and separation on the C9N7 surface was revealed. The closer the adsorption distance, the stronger the interaction energy between the gas molecule and the C9N7 surface. The strong interaction between the C9N7 nanosheet and the CO2 molecule contributes to its impressive CO2 uptake and selectivity performance, suggesting that the C9N7 slit could be a promising candidate for CO2 capture and separation.

Targeted regulation of FoxO1 in chondrocytes prevents age-related osteoarthritis via autophagy mechanism.

Autophagy is designated as a biological recycling process to maintain cellular homeostasis by the sequestration of damaged proteins and organelles in plasma and cargo delivery to lysosomes for degradation and reclamation. This organelle recycling process promotes chondrocyte homeostasis and has been previously implicated in osteoarthritis (OA). Autophagy is widely involved in regulating chondrocyte degeneration markers such as MMPs, ADAMSTs and Col10 in chondrocytes. The critical autophagy-related (ATG) proteins have now been considered the protective factor against late-onset OA. The current research field proposes that the autophagic pathway is closely related to chondrocyte activity. However, the mechanism is complex yet needs precise elaboration. This review concluded that FoxO1, a forkhead O family protein, which is a decisive mediator of autophagy, facilitates the pathological process of osteoarthritis. Diverse mechanisms regulate the activity of FoxO1 and promote the initiation of autophagy, including the prominent AMPK and Sirt-2 cellular pathways. FoxO1 transactive is regulated by phosphorylation and acetylation processes, which modulates the downstream ATGs expression. Furthermore, FoxO1 induces autophagy by directly interacting with ATGs proteins, which control the formation of autophagosomes and lysosomes fusion. This review will discuss cutting-edge evidence that the FoxO-autophagy pathway plays an essential regulator in the pathogenesis of osteoarthritis.

Management of Meloidogyne incognita on Cucumber with a New Nonfumigant Nematicide Fluopimomide.

Cucumber (Cucumis sativus L.) is an economically important vegetable crop in China. Southern root-knot nematode (Meloidogyne incognita) is a significant obstacle in cucumber production, causing severe root damage and yield losses. Moreover, resistance development to fosthiazate, and poor mobility of abamectin, have led to failure to control this nematode. It is of great interest to growers and the vegetable industry to explore novel nonfumigant nematicides that can provide adequate control in an environmentally friendly manner. Fluopimomide (FM), a new chemical having a similar structure to fluopyram, was shown to exhibit toxic effects on fungi and nematodes. The efficacy of FM to reduce infection of M. incognita in cucumber was evaluated under greenhouse and field conditions. In the greenhouse, FM at all test rates resulted in a 22.5 to 39.6% and 31.3 to 55.0% reduction in the population density of M. incognita in the soil at 30 and 60 days after treatment (DAT), respectively, compared with the nontreated control. FM at 500 and 750 g ha-1 reduced (P < 0.05) root galling, meanwhile increasing plant height compared with the nontreated control at 30 and 60 DAT. In the field trials, FM at 500 and 750 g ha-1 decreased the population density of M. incognita and root galling 57.2 to 69.9% compared with the untreated control, while enhancing cucumber yield in two consecutive years. Furthermore, FM at 500 g ha-1 combined with fosthiazate was the most effective treatment showing a synergistic effect on reducing population densities of M. incognita, which was significantly greater than either FM or fosthiazate by themselves. In summary, FM has considerable potential for managing M. incognita on cucumber.

A density functional theory study of Fe(II)/Fe(III) distribution in single layer green rust: a cluster approach.

Green rust (GR) is a potentially important compound for the reduction of heavy metal and organic pollutants in subsurface environment because of its high Fe(II) content, but many details of the actual reaction mechanism are lacking. The reductive capacity distribution within GR is a key to understand how and where the redox reaction occurs and computational chemistry can provide more details about the electronic properties of green rust. We constructed three sizes of cluster models of single layer GR (i.e., without interlayer molecules or ions) and calculated the charge distribution of these structures using density functional theory. We found that the Fe(II) and Fe(III) are distributed unevenly in the single layer GR. Within a certain range of Fe(II)/Fe(III) ratios, the outer iron atoms behave more like Fe(III) and the inner iron atoms behave more like Fe(II). These findings indicate that the interior of GR is more reductive than the outer parts and will provide new information to understand the GR redox interactions.

Design of a Single Channel Modulated Wideband Converter for Wideband Spectrum Sensing: Theory, Architecture and Hardware Implementation.

In a cognitive radio sensor network (CRSN), wideband spectrum sensing devices which aims to effectively exploit temporarily vacant spectrum intervals as soon as possible are of great importance. However, the challenge of increasingly high signal frequency and wide bandwidth requires an extremely high sampling rate which may exceed today's best analog-to-digital converters (ADCs) front-end bandwidth. Recently, the newly proposed architecture called modulated wideband converter (MWC), is an attractive analog compressed sensing technique that can highly reduce the sampling rate. However, the MWC has high hardware complexity owing to its parallel channel structure especially when the number of signals increases. In this paper, we propose a single channel modulated wideband converter (SCMWC) scheme for spectrum sensing of band-limited wide-sense stationary (WSS) signals. With one antenna or sensor, this scheme can save not only sampling rate but also hardware complexity. We then present a new, SCMWC based, single node CR prototype System, on which the spectrum sensing algorithm was tested. Experiments on our hardware prototype show that the proposed architecture leads to successful spectrum sensing. And the total sampling rate as well as hardware size is only one channel's consumption of MWC.

Water promoting electron hole transport between tyrosine and cysteine in proteins via a special mechanism: double proton coupled electron transfer.

The proton/electron transfer reactions between cysteine residue (Cys) and tyrosinyl radical (Tyr(•)) are an important step for many enzyme-catalyzed processes. On the basis of the statistical analysis of protein data bank, we designed three representative models to explore the possible proton/electron transfer mechanisms from Cys to Tyr(•) in proteins. Our ab initio calculations on simplified models and quantum mechanical/molecular mechanical (QM/MM) calculations on real protein environment reveal that the direct electron transfer between Cys and Tyr(•) is difficult to occur, but an inserted water molecule can greatly promote the proton/electron transfer reactions by a double-proton-coupled electron transfer (dPCET) mechanism. The inserted H2O plays two assistant roles in these reactions. The first one is to bridge the side chains of Tyr(•) and Cys via two hydrogen bonds, which act as the proton pathway, and the other one is to enhance the electron overlap between the lone-pair orbital of sulfur atom and the π-orbital of phenol moiety and to function as electron transfer pathway. This water-mediated dPCET mechanism may offer great help to understand the detailed electron transfer processes between Tyr and Cys residues in proteins, such as the electron transfer from Cys439 to Tyr730(•) in the class I ribonucleotide reductase.

Experimental study on soil deformation caused by overexploitation of groundwater.

Due to the overexploitation of deep groundwater, the largest cone of depression in the world has formed in the North China Plain. This led to severe geological hazards, including land subsidence and ground fissures, and also caused economic losses. The prevention and treatment of subsidence needs to rely on the accurate prediction of subsidence amount. According to the one-dimensional consolidation theory and effective stress principle, combined with stratum structure, groundwater flow, stress distribution, and so forth, the high-pressure consolidation test results of 569.6 m deep borehole soil samples are adopted; with a specific focus on stress and deformation parameters under exploitation of groundwater condition, the soil-water coupling prediction model of groundwater level lowering depth and land subsidence has been established. Verification with measured subsidence data near the study sites demonstrated that the predicted curve is consistent with the measured one and the differences between them are acceptable. The model can be applied in different areas after making adjustment based on different regional stratigraphic structures. Its key advantage lies in the ability to provide land subsidence prediction for areas lacking monitoring data, making it highly valuable for widespread application. PRACTITIONER POINTS: There is a compressible stratum structure; it is the internal factors of land subsidence. The groundwater level decline causes the soil body stress to change. It is land subsidence of the external factors. Based on the one-dimensional consolidation theory and by combining stratigraphic structures, groundwater flow, and stress distribution, a ground settlement prediction model was established.

RBM3 Inhibits the Cell Cycle of Cutaneous Squamous Cell Carcinoma through the PI3K/AKT Signaling Pathway.

BACKGROUND: RBM3 is a key RNA-binding protein that has been implicated in various cellular processes, including cell proliferation and cell cycle regulation. However, its role in cutaneous squamous cell carcinoma (cSCC) remains poorly understood. AIMS: We aimed to investigate the expression levels of RNA-binding motif protein 3 (RBM3) in patients with cSCC and evaluate its effect on cell ability in cSCC and its underlying regulatory mechanisms. METHODS: The expression of RBM3 in cSCC tissues and A431 cells was determined via immunohistochemistry and western blotting. Plenti-CMV-RBM3- Puro was used to overexpress RBM3. The effect of RBM3 on the proliferation ability of cSCC cells was evaluated using MTT and colony formation assay. Cell apoptosis and cell cycle were determined using flow cytometry, while the protein expressions of BAX, NF-κB, BCL2, CASPASE 3, CYCLIN B, CYCLIN E, CDK1, phosphorylated (P)-CDK1, CDK2, P-CDK2, ERK, P-ERK, P-AMPK, AKT, P-AKT, MDM2, and P53 were assessed using western blotting. RESULTS: RBM3 expression was significantly downregulated in cSCC tissues and A431 cells. RBM3 overexpression significantly inhibited the cell proliferation and colony formation ability of A431. Notably, RNA-seq results showed that the differentially expressed genes associated with RBM3 were primarily involved in the regulation of the cell cycle, oocyte meiosis, and P53 signaling pathway, as well as the modulation of the MAPK, AMPK, Hippo, mTOR, PI3K/AKT, Wnt, FoxO, and NF-κB signaling pathways. Additionally, our findings demonstrated that overexpression of RBM3 inhibited cell proliferation and induced cell cycle arrest of cSCC through modulation of the PI3K/AKT signaling pathway. CONCLUSION: This study provides novel insights into the suppressive roles of RBM3 in cell proliferation and the cell cycle in cSCC and highlights its therapeutic potential for cSCC.

Study on the response mechanisms and evolution prediction of groundwater microbial-toxicological indicators.

This study aims to investigate the response mechanisms of groundwater microbial-toxicological indicators, specifically total bacteria count (TBC) and total coliform count (TCC), to water quality indicators and environmental conditions. Using data from a water source in the western plateau of China, a predictive model focusing on TBC and TCC was developed. An orthogonal experimental design was employed to manipulate environmental conditions such as temperature, pH, and porosity, facilitating laboratory experiments. These experiments measured pH, chemical oxygen demand (COD), oxidation-reduction potential (ORP), TBC, and TCC at varying depths and environmental conditions. Principal component analysis elucidated the mechanisms by which water quality indicators and environmental conditions affect groundwater microbial-toxicological indicators. A prediction model for these indicators in plateau regions was established based on a backpropagation neural network (BP-NN), using TBC and TCC as target variables and the newly extracted principal components as influencing factors. The results demonstrate that environmental conditions and water quality indicators primarily influence the evolution of groundwater microbial-toxicological indicators by altering the ionic charge quantities, redox conditions, and temperature of the groundwater. The predictive model for groundwater microbial-toxicological indicators shows trends consistent with experimental outcomes, with an average relative error of less than 15%, meeting engineering requirements. PRACTITIONER POINTS: The values of total bacteria count (TBC) and total coliform count (TCC) under different conditions were obtained by column experiments. The influence mechanism of environmental conditions and groundwater indicators on TBC and TCC was elaborated by principal component analysis. TBC and TCC prediction models were established through the investigation of water sources in a plateau area and laboratory experiments.

Relationship between preoperative hemoglobin levels and length of stay in elderly patients with hip fractures: A retrospective cohort study.

Globally, hip fractures in elderly individuals are a prevalent and serious issue. Patients typically have a longer length of stay (LOS), which increases the risk of complications and increases hospitalization costs. Hemoglobin (Hb) is a routine blood test that is associated with disease prognosis. This study aimed to investigate the relationship between preoperative Hb and LOS in elderly hip fracture patients and to determine a reliable transfusion threshold. The clinical data of hip fracture patients (aged ≥ 60 years) admitted to the Department of Orthopaedics, Shenzhen Second People's Hospital, between January 2012 and December 2021 were retrospectively analyzed. Multiple linear regression analysis was used to assess the linear relationship between preoperative Hb and LOS. Smooth curve fitting was performed to investigate potential nonlinear relationships. In the case of discovering nonlinear relationships, a weighted two-piecewise linear regression model was built, and the inflection points were determined using a recursive algorithm. Subgroup analyses were conducted based on age and gender. A total of 1444 patients with an average age of (77.54 ±â€…8.73) years were enrolled. After adjusting for covariates, a nonlinear relationship was found between preoperative Hb and LOS. The two-piecewise linear regression model revealed an inflection point of 10 g/dL. On the left of the inflection point (Hb < 10 g/dL), the LOS was reduced by 0.735 days for every 1 g/dL increase in Hb (ß = -0.735, 95% confidence interval: -1.346 to -0.124, P = .019). On the right side of the inflection point (Hb > 10 g/dL), the relationship was not statistically significant (ß = 0.001, 95% confidence interval: -0.293 to 0.296, P = .992). In elderly hip fracture patients, there is a nonlinear association between preoperative Hb and LOS. However, when Hb levels were <10 g/dL, there was a negative correlation with the LOS. No correlation was observed when Hb levels were >10 g/dL. These findings underscore the importance of timely intervention to manage Hb levels in elderly patients with hip fractures, potentially reducing hospitalization durations and associated complications.

Ecological and geological security risk assessment of underground space development in cold and arid canyon cities-Taking Ping'an District, Haidong City, Qinghai Province, as an example.

The ecological and geological problems caused by the rise of groundwater level due to the development of underground space in cold and arid canyon cities are particularly typical. Reasonably assessing the ecological and geological security risks of utilizing underground space is conducive to reducing the occurrence of ecological and geological problems during the construction and operation of underground engineering projects. Taking Ping'an District of Haidong City as an example, the topography and geomorphology of the research area were investigated in the field, and the distribution of topography and geomorphology in the research area was understood; through geological drilling and geotechnical engineering testing, the distribution of different strata in the research area was obtained; through pumping and seepage experiments, the recharge, runoff, and discharge relationship between surface water and groundwater in the research area and the water abundance of different strata are obtained, and the causes and mechanisms of geological safety risks in forest and grassland ecosystems, farmland ecosystems, and human settlements ecosystems were analyzed based on literature. Corresponding ecological geological safety risk assessment index systems and methods were established, and the ecological geological safety risks before and after the development of underground rail transit projects along both banks of the Huangshui River in the study area were evaluated. PRACTITIONER POINTS: The development of underground space in canyon type cities can easily lead to ecological and geological problems. Taking Haidong City, Qinghai Province, as an example, this study investigates the causes of ecological and geological problems caused by the development of underground spaces in canyon type cities. An ecological geological security risk assessment index system and method for canyon-type cities were established. An evaluation was conducted on the ecological and geological safety risks before and after the development of the underground rail transit projects on both sides of the research area.

Basal metabolic rate mediates the causal relationship between gut microbiota and osteoarthritis: a two-step bidirectional Mendelian randomization study.

Background: The relationship between gut microbiota and osteoarthritis (OA) occurrence remains unclear. Existing research needs to clearly understand how basal metabolic rate (BMR) regulates this relationship. Therefore, using a two-step bidirectional Mendelian Randomization approach, our study aims to investigate whether BMR levels mediate the causal relationship between gut microbiota and OA. Methods: In this study, we examined publicly available summary statistics from Genome-Wide Association Studies (GWAS) to determine the correlation between gut microbiota and OA. The analysis included one primary dataset and two secondary datasets. Initially, a two-step, two-sample, and reverse MR analysis was performed to identify the causal relationship between gut microbiota and OA. Subsequently, a two-step MR analysis revealed that the relationship between microbiota and OA is mediated by BMR. Sensitivity analyses confirmed the robustness of the study results. Results: In our analysis of the primary dataset, we discovered a positive correlation between three taxa and the outcome of OA, and eight taxa exhibited a negative correlation with the OA outcome. Through comparisons with the secondary dataset and multiple testing corrections, we found a negative association between the class Actinobacteria (OR=0.992886277, p-value = 0.003) and the likelihood of OA occurrence. Notably, knee osteoarthritis (KOA) and hip osteoarthritis (HOA) had a strong negative correlation (OR = 0.927237553/0.892581219). Our analysis suggests that BMR significantly mediates the causal pathway from Actinobacteria to OA, with a mediated effect of 2.59%. Additionally, BMR mediates 3.98% of the impact in the path from the order Bifidobacteriales and the family Bifidobacteriaceae to OA. Besides these findings, our reverse analysis did not indicate any significant effect of OA on gut microbiota or BMR. Conclusion: Our research results indicate that an increase in the abundance of specific gut microbial taxa is associated with a reduced incidence of OA, and BMR levels mediate this causal relationship. Further large-scale randomized controlled trials are necessary to validate the causal impact of gut microbiota on the risk of OA. This study provides new insights into the potential prevention of OA by modulating the gut microbiota.

Panoramic heat map for spatial distribution of necrotic lesions.

Aims: In this study, we aimed to visualize the spatial distribution characteristics of femoral head necrosis using a novel measurement method. Methods: We retrospectively collected CT imaging data of 108 hips with non-traumatic osteonecrosis of the femoral head from 76 consecutive patients (mean age 34.3 years (SD 8.1), 56.58% male (n = 43)) in two clinical centres. The femoral head was divided into 288 standard units (based on the orientation of units within the femoral head, designated as N[Superior], S[Inferior], E[Anterior], and W[Posterior]) using a new measurement system called the longitude and latitude division system (LLDS). A computer-aided design (CAD) measurement tool was also developed to visualize the measurement of the spatial location of necrotic lesions in CT images. Two orthopaedic surgeons independently performed measurements, and the results were used to draw 2D and 3D heat maps of spatial distribution of necrotic lesions in the femoral head, and for statistical analysis. Results: The results showed that the LLDS has high inter-rater reliability. As illustrated by the heat map, the distribution of Japanese Investigation Committee (JIC) classification type C necrotic lesions exhibited clustering characteristics, with the lesions being concentrated in the northern and eastern regions, forming a hot zone (90% probability) centred on the N4-N6E2, N3-N6E units of outer ring blocks. Statistical results showed that the distribution difference between type C2 and type C1 was most significant in the E1 and E2 units and, combined with the heat map, indicated that the spatial distribution differences at N3-N6E1 and N1-N3E2 units are crucial in understanding type C1 and C2 necrotic lesions. Conclusion: The LLDS can be used to accurately measure the spatial location of necrotic lesions and display their distribution characteristics.

Wedelolactone alleviates inflammation and cartilage degeneration by suppressing the NF-κB signaling pathway in osteoarthritis.

Inflammation and extracellular matrix (ECM) degradation are two major factors involved in the pathogenesis of osteoarthritis (OA). Wedelolactone, a natural compound classified as a coumestan, is isolated from the medicinal plants Eclipta alba and Wedelia calendulacea. In this study, we assessed the protective effects of Wedelolactone on chondrocytes in OA. Our findings show that pretreatment with Wedelolactone effectively inhibited the IL-1ß-induced upregulation of COX­2, iNOS, TNF-α, and IL6 in chondrocytes, contributing to inflammation suppression. Moreover, pretreatment with Wedelolactone followed by IL-1ß treatment significantly increased the expression of Collagen II and SOX9, while decreasing the expression of Adamts5, MMP1, MMP3, and MMP13, thereby promoting ECM protection. Through Network pharmacology Analysis, we identified 14 key targets that link Wedelolactone and OA. GO and KEGG pathway analysis suggested that Wedelolactone primarily impacted OA by targeting inflammatory responses, particularly the NF-κB signaling pathway. Further studies demonstrated Wedelolactone prevented IL-1ß-induced activation of NF-κB signaling pathway by inhibiting the translocation of p65 and the preventing the degradation of IκBα in human chondrocytes. Molecular docking studies also indicated that Wedelolactone can directly bind to the NF-κB complex, thereby inhibited the nuclear localization of p65. In vivo experiments demonstrated that Wedelolactone can alleviate cartilage damage in DMM mice model. In summary, Wedelolactone appears to mitigate inflammation and cartilage degeneration by suppressing the NF-κB signaling pathway, thereby alleviating OA progression. Our results suggested Wedelolactone may offer therapeutic advantages for OA treatment.

Identification of carbon fixation microorganisms and pathways in an aquifer contaminated with long-chain petroleum hydrocarbons.

Petroleum hydrocarbons (PHCs) can be biodegraded into CO2, and PHC-contaminated aquifers are always deemed as carbon sources. Fortunately, some carbon fixation microorganisms have been found in PHC-contaminated sites. However, most of the studies are related to volatile short-chain PHC, and few studies focus on long-chain PHC-contaminated sites. To reveal the carbon fixation microorganisms in these sites, in the study, a long-chain PHC polluted site in North China was selected. Through hydrochemical and metagenomics analysis, the structure and capacity of carbon fixing microorganisms in the site were revealed. Results showed that there were many kinds of carbon fixed microorganisms that were identified such as Flavobacterium, Pseudomonas. HP/4HB, rTCA, and DC/4HB cycles were dominated carbon fixation pathways. The long-chain PHC were weakly correlated with carbon fixation microorganisms, but it may stimulate the growth of some carbon fixation microorganisms, such as microorganisms involved in rTCA cycle. PRACTITIONER POINTS: The microorganisms with carbon fixation gene exist in the aquifer contaminated by long-chain petroleum hydrocarbon. Microorganisms that have the ability to degrade petroleum also have the ability to carbon fixation. Long-chain petroleum hydrocarbon may promote the growth of carbon fixation microorganisms.