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As two pivotal regulatory factors in cancer biology, oxidative stress and inflammation interact dynamically through complex network mechanisms to influence tumor initiation, progression, and treatment resistance. Oxidative stress induces genomic instability, oncogenic signaling activation, and tumor microenvironment (TME) remodeling via the abnormal accumulation of reactive oxygen species (ROS) or reactive nitrogen species (RNS). Conversely, inflammation sustains malignant phenotypes by releasing pro-inflammatory cytokines and chemokines and promoting immune cell infiltration. These processes create a vicious cycle via positive feedback loops whereby oxidative stress initiates inflammatory signaling, while the inflammatory milieu further amplifies ROS/RNS production, collectively promoting proliferation, migration, angiogenesis, drug resistance, and immune evasion in tumor cells. Moreover, their crosstalk modulates DNA damage repair, metabolic reprogramming, and drug efflux pump activity, significantly impacting the sensitivity of cancer cells to chemotherapy, radiotherapy, and targeted therapies. This review systematically discusses these advances and the molecular mechanisms underlying the interplay between oxidative stress and inflammation in cancer biology. It also explores their potential as diagnostic biomarkers and prognostic indicators and highlights novel therapeutic strategies targeting the oxidative stress–inflammation axis. The goal is to provide a theoretical framework and translational roadmap for developing synergistic anti-tumor therapies.

Abstract This review aimed to provide a comprehensive analysis of the etiology, epidemiology, pathology, and conventional treatment of heterotopic ossification (HO), especially emerging potential therapies. HO is the process of ectopic bone formation at non-skeletal sites. HO can be subdivided into two major forms, acquired and hereditary, with acquired HO predominating. Hereditary HO is a rare and life-threatening genetic disorder, but both acquired and hereditary form can cause severe complications, such as peripheral nerve entrapment, pressure ulcers, and disability if joint ankylosis develops, which heavily contributes to a reduced quality of life. Modalities have been proposed to treat HO, but none have emerged as the gold standard. Surgical excision remains the only effective modality; however, the optimal timing is controversial and may cause HO recurrence. Recently, potential therapeutic strategies have emerged that focus on the signaling pathways involved in HO, and small molecule inhibitors have been shown to be promising. Moreover, additional specific targets, such as small interfering RNAs (siRNAs) and non-coding RNAs, could be used to effectively block HO or develop combinatorial therapies for HO.

The Aquila Optimizer (AO) is a novel and efficient optimization algorithm inspired by the hunting and searching behavior of Aquila. However, the AO faces limitations when tackling high-dimensional and complex optimization problems due to insufficient search capabilities and a tendency to prematurely converge to local optima, which restricts its overall performance. To address these challenges, this study proposes the Multi-Strategy Aquila Optimizer (MSAO) by integrating multiple enhancement techniques. Firstly, the MSAO introduces a random sub-dimension update mechanism, significantly enhancing its exploration capacity in high-dimensional spaces. Secondly, it incorporates memory strategy and dream-sharing strategy from the Dream Optimization Algorithm (DOA), thereby achieving a balance between global exploration and local exploitation. Additionally, the MSAO employs adaptive parameter and dynamic opposition-based learning to further refine the AO's original update rules, making them more suitable for a multi-strategy collaborative framework. In the experiment, the MSAO outperform eight state-of-the-art algorithms, including CEC-winning and enhanced AO variants, achieving the best optimization results on 55%, 69%, 69%, and 72% of the benchmark functions, respectively, which demonstrates its outstanding performance. Furthermore, ablation experiments validate the independent contributions of each proposed strategy, and the application of MSAO to five engineering problems confirms its strong practical value and potential for broader adoption.

This study investigates the relationship between online media attention and the performance of China’s green funds. The results show that increased media attention can boost the performance of green funds in the short term, however, this effect is short-lived. The mechanism of short-term positive effects may be due to increased media attention leading to larger purchases, which may undermine funds’ long-term performance. In particular, online media attention has a greater impact on larger and older funds. Moreover, it indicates that media attention reduces the returns of individual investor-dominated funds, but has little effect on institutional investor-dominated funds.

The impaired repair of intestinal mucosal damage is an important pathological feature of ulcerative colitis (UC). The critical role of intestinal epithelial cells (IECs) proliferation and migration in the repair of damaged mucosal epithelium has been well established. However, the molecular circuitry that decodes IECs sense intestinal mucosal damage signals to initiate and drive repair program remains elusive. Here, we identify a tryptophan (Trp) metabolic gatekeeping mechanism wherein G protein-coupled receptor 35 (GPR35) senses intestinal mucosal damage through monitoring Trp-kynurenine (KYN)-kynurenic acid (KA) axis metabolism with a unique “sandwich” structural binding mode. We delineate a GPR35-Kruppel-like factor 5 (KLF5) regulatory circuit in which KLF5 serves as the central effector, translating GPR35-mediated KA sensing into repair programming through PI3K-AKT-mTOR signaling cascade. This circuitry precisely orchestrates IECs proliferation and migration by regulating KLF5-dependent gene expression networks that essential for restoring damaged mucosa. Once this metabolic gatekeeping system is disrupted, either through impaired GPR35-mediated KA sensing or defective signal transduction, compromises damage signal decoding, leading to inadequate repair responses. Such dysregulation results in delayed intestinal mucosal repair and exacerbation of tissue damage. Our findings highlight GPR35 as a surveillant of abnormal Trp-KYN-KA axis metabolism, enabling IECs to detect intestinal mucosal damage and orchestrate repair through KLF5 response. This provides important implications for UC prevention and treatment by targeting GPR35-KLF5 circuit.

Metabolic-associated fatty liver disease (MAFLD) has emerged as a global health crisis, which is characterized by hepatic lipid accumulation, inflammation, and fibrosis. Currently, effective therapeutic strategies for MAFLD are still scarce. This study aimed to explore the hepatoprotective effects and underlying mechanisms of total flavones from Abelmoschus manihot (L.) Medik. (Malvaceae), abbreviated as TFA, in the context of MAFLD. Ultra-high-performance liquid chromatography-quadrupole orbitrap mass spectrometry (UHPLC-QTOF-MS) was used to identify the metabolites in TFA. MAFLD mice induced by a high-fat diet were treated with TFA at doses of 50 and 100 mg/kg. Body weight gain, hepatic lipid accumulation, and serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total cholesterol (TC), and triglycerides (TG) were determined. Histological analysis was performed to evaluate hepatic steatosis, fibrosis, as well as the levels of inflammatory cytokines (IL-6, TNF-α) and antioxidant markers (SOD, GSH). Transcriptomic and metabolomic analyses were carried out to explore the molecular mechanisms. In vitro studies were conducted in HepG2 cells, and the role of autophagy was investigated using the autophagy inhibitor 3-MA. Using UHPLC-QTOF-MS, 56 metabolites were identified in TFA, including hyperoside, rutin, and quercetin derivatives, which possess anti-lipidemic and anti-inflammatory properties. In MAFLD mice, TFA treatment significantly decreased body weight gain, hepatic lipid accumulation, and the serum levels of ALT, AST, TC, and TG. Histological analysis demonstrated that TFA alleviated hepatic steatosis and fibrosis, with decreased levels of inflammatory cytokines and increased antioxidant markers. Transcriptomic and metabolomic analyses indicated that TFA regulated nucleotide metabolism, pyrimidine metabolism, and the PI3K/AKT/mTOR signaling pathway. In HepG2 cells, TFA inhibited palmitic acid/oleic acid-induced lipid deposition and the production of reactive oxygen species (ROS). Mechanistically, TFA activated autophagy through the inhibition of PI3K/AKT/mTOR phosphorylation, as demonstrated by the increased LC3II/I conversion and decreased p62 expression. The autophagy inhibitor 3-MA abolished the protective effects of TFA. Our findings suggest that TFA ameliorates MAFLD via promoting PI3K/AKT/mTOR-mediated autophagy. The metabolites identified in TFA might contribute to its multi-target therapeutic effects. Considering the limited treatment options for MAFLD, TFA exhibits great potential as a novel therapeutic agent for MAFLD intervention, thus justifying further preclinical and clinical investigations.

Background Patellofemoral osteoarthritis (PFJOA) is a subtype of knee OA, which is one of the main causes of anterior knee pain. The current study found an increased prevalence of OA in postmenopausal women, called postmenopausal OA. Therefore, we designed the ovariectomized rat model of patella baja-induced PFJOA. Alendronate (ALN) inhibits osteoclast-mediated bone loss, and has been reported the favorable result of a potential intervention option of OA treatment. However, the potential effects of ALN treatment on PFJOA in the ovariectomized rat model are unknown and need further investigation prior to exploration in the clinical research setting. In this study, the effects of ALN on articular cartilage degradation and subchondral bone microstructure were assessed in the ovariectomized PFJOA rat model for 10 weeks. Methods Patella baja and estrogen withdrawal were induced by patellar ligament shortening (PLS) and bilateral ovariectmomy surgeries in 3-month-old female Sprague–Dawley rats, respectively. Rats were randomly divided into five groups (n = 8): Sham + V; OVX + V, Sham + PLS + V, OVX + PLS + V, OVX + PLS + ALN (ALN: 70 μg/kg/week). Radiography was performed to evaluate patellar height ratios, and the progression of PFJOA was assessed by macroscopic and microscopic analyses, immunohistochemistry and micro-computed tomography (micro-CT). Results Our results found that the patella baja model prepared by PLS can successfully cause degeneration of articular cartilage and subchondral bone, resulting in changes of PFJOA. OVX caused a decrease in estrogen levels in rats, which aggravated the joint degeneration caused by PFJOA. Early application of ALN can delay the degenerative changes of articular cartilage and subchondral bone microstructure in castrated PFJOA rat to a certain extent, improve and maintain the micrometabolism and structural changes of cartilage and subchondral bone. Conclusion The early application of ALN can delay the destruction of articular cartilage and subchondral bone microstructure in castrated PFJOA rat to a certain extent.

Developing low-carbon agriculture can effectively avoid the waste of natural resources, thus contributing to the long-term sustainability of agriculture. This study uses the Super-SBM model to measure agricultural low-carbon economic efficiency (ALEE) in China from 2000 to 2018, then analyzes the spatial-temporal evolution characteristics. Simultaneously, the influencing factors of ALEE are investigated using spatial econometric model. The results show that: (1) In terms of temporal evolution, the ALEE in most provinces is declined over time, with only a few provinces improving. The ALEE in China and the three regions all show an obvious “L” trend of decline first and then stability. (2) From the perspective of spatial differentiation, provinces in eastern region have higher ALEE, while those in central and western regions have lower ALEE. Hainan’s ALEE has an absolute advantage, while Shanxi is the worst. (3) China’s ALEE shows obvious spatial agglomeration characteristics of H-H and L-L agglomeration, which are further enhanced over time. The number of L-L agglomeration provinces gradually increases, indicating that China’s ALEE has not been improved significantly. (4) Economic growth level and Agricultural scientific and Technological progress have effectively improved the ALEE. However, Capital deepening, Government fiscal expenditure, Agricultural planting structure, and Agricultural disaster all have negative impacts. Rural electricity consumption also has a negative impact, but the impact is not significant. To accelerate the development of low-carbon agriculture, all regions must not only pursue a differentiated low-carbon agriculture development path, but also accelerate agricultural transformation, strengthen research and development, and popularize low-carbon agricultural technologies, reduce the input of traditional agricultural means of production, optimize the agricultural industrial structure, and adjust agricultural subsidy policies.

The chemical compositions and anti-tumor activities of the petroleum ether fraction (PE), from mushroom Pyropolyporus fomentarius, were studied. Upon gas chromatography-mass spectrometry (GC-MS) analysis, nine major constituents were identified in the fraction. In vitro, the PE showed cytotoxic activity against murine sarcoma S180 (S180) cells in a dose- and time-dependent manner, and the cytotoxic effects were associated with apoptosis. The mitochondrial membrane potential loss and the intracellular ROS generation were greatly increased in the Pyropolyporus fomentarius PE treated group, suggesting cell apoptosis, induced by the PE in S180 cells, might be mitochondria dependent and ROS mediated. Consistent with in vitro findings, the in vivo study showed that the Pyropolyporus fomentarius PE was also effective in inhibiting the tumor growth induced by S180 cells and had lower immune organ toxicity. We found that the Pyropolyporus fomentarius PE has significant anti-tumor activity and great potential in screening anti-tumor drugs.

ObjectivesThis work aimed to analyse the risk factors for poor outcomes and mortality among patients with anterior large vessel occlusion (LVO) ischaemic stroke, despite successful recanalisation.Setting and participantsThis study conducted a secondary analysis among patients who underwent successful recanalisation in the CAPTURE trial. The trial took place between March 2018 and September 2020 at 21 sites in China. The CAPTURE trial enrolled patients who had an acute ischaemic stroke aged 18–80 years with LVO in anterior circulation.InterventionsThrombectomy was immediately performed using Neurohawk or the Solitaire FR after randomisation in CAPTURE trial. Rescue treatment was available for patients with severe residual stenosis caused by atherosclerosis.Primary and secondary outcome measuresThe primary goal was to predict poor 90-day survival or mortality within 90 days post-thrombectomy. Univariate analysis, using the χ2 test or Fisher’s exact test, was conducted for each selected factor. Subsequently, a multivariable analysis was performed on significant factors (p≤0.10) identified through univariate analysis using the backward selection logistic regression approach.ResultsAmong the 207 recruited patients, 79 (38.2%) exhibited poor clinical outcomes, and 26 (12.6%) died within 90 days post-thrombectomy. Multivariate analysis revealed that the following factors were significantly associated with poor 90-day survival: age ≥67 years, internal carotid artery (ICA) occlusion (compared with middle cerebral artery (MCA) occlusion), initial National Institutes of Health Stroke Scale (NIHSS) score ≥17 and final modified Thrombolysis in Cerebral Infarction (mTICI) score 2b (compared with mTICI 3). Additionally, the following factors were significantly associated with mortality 90 days post-thrombectomy: initial NIHSS score ≥17, ICA occlusion (compared with MCA occlusion) and recanalisation with more than one pass.ConclusionsAge, NIHSS score, occlusion site, mTICI score and the number of passes can be independently used to predict poor 90-day survival or mortality within 90 days post-thrombectomy.Trial registration numberNCT04995757.