A Nomogram Including Sarcopenia for Predicting Progression-Free Survival in Patients with Localized Papillary Renal Cell Carcinoma: A Retrospective Cohort Study.

BACKGROUND: Because of to the removal of subclassification of papillary renal cell carcinoma (pRCC), the survival prognostification of localized pRCC after surgical treatment became inadequate. Sarcopenia was widely evaluated and proved to be a predictive factor for prognosis in RCC patients. Therefore, we comprehensively investigated the survival prediction of the body composition parameters for localized pRCC. METHODS: Patients pathologically diagnosed with pRCC between February 2012 and February 2022 in our center were enrolled. The body composition parameters, including skeletal muscle index (SMI), subcutaneous adipose tissue (SAT), and perirenal adipose tissue (PRAT), were measured by the images of preoperative computed tomography (CT). The primary outcome was set as progression-free survival (PFS), and the cutoff values of body composition parameters were calculated by using the Youden from receiver operating characteristic curve (ROC) curves. Univariate and multivariate Cox proportional regression analyses were performed to explore independent risk factors for survival prediction. Then, significant factors were used to construct a prognostic nomogram. The performance of the nomogram was evaluated by Harrell's C-index, calibration curves and time-dependent ROC curves. RESULTS: A total of 105 patients were enrolled for analysis. With a median follow-up time of 30.48 months, 25 (23.81%) patients experienced cancer progression. The percentage of sarcopenia was 74.29%. Univariate Cox analysis identified that gender, PRAT, SAT, skeletal muscle (SM), sarcopenia, surgical technique, and tumor diameter were associated with progression. Further multivariate analysis showed that sarcopenia (hazard ratio [HR] 0.15, 95% confidence interval [CI] 0.03-0.66), SAT (HR 6.36, 95% CI 2.39-16.93), PRAT (HR 4.66, 95% CI 1.77-12.27), tumor diameter (HR 0.35, 95% CI 0.14-0.86), and surgical technique (HR 2.85, 95% CI 1.06-7.64) were independent risk factors for cancer progression. Then, a prognostic nomogram based on independent risk factors was constructed and the C-index for progression prediction was 0.831 (95% CI 0.761-0.901), representing a reasonable discrimination, the calibration curves, and the time-dependent ROC curves verified the good performance of the nomogram. CONCLUSIONS: A prognostic nomogram, including sarcopenia, SAT, PRAT, tumor diameter, and surgical technique, was constructed to calculate the probability of progression for localized pRCC patients and needs further external validation for clinical use in the future.

Enhanced bone cement distribution in percutaneous vertebroplasty using a curved guide wire: a propensity score matching analysis.

BACKGROUND: Osteoporotic vertebral compression fractures (OVCF) severely affect the quality of life in the aged population. Percutaneous vertebroplasty (PVP) alleviates pain and stabilizes vertebrae, but suboptimal bone cement distribution can cause complications. Hence, this study aimed to clarify whether a new technique for PVP, using a curved guide wire, enhances the distribution of bone cement and improves clinical outcomes in patients with OVCF. METHODS: Patients with single-segment OVCF underwent PVP or curved guide wire percutaneous vertebroplasty (C-PVP). Propensity score matching (PSM) was employed to balanced the baseline characteristics. The primary outcomes were the visual analog scale (VAS) and Oswestry disability index (ODI) scores. The secondary outcomes included assessments of bone cement distribution, bone cement injection volume, radiological parameters, and general clinical results. Additionally, Complications and adverse events were documented. RESULTS: After PSM analysis, each group comprised 54 patients, which significantly reduced baseline differences. The C-PVP group showed better clinical outcomes compared to the traditional PVP group. One month after surgery, the C-PVP group had significantly lower VAS and ODI scores (p < 0.001). These improvements persisted at six months and the final follow-up. Additionally, bone cement distribution scores were better (p < 0.001), injection volume was higher (p = 0.03), leakage was less frequent (p = 0.02), and adjacent vertebral fractures occurred less frequently (p = 0.04) in the C-PVP group. Radiological parameters and overall clinical outcomes revealed no significant differences between the two groups. CONCLUSION: The use of curved guide wire in PVP significantly improves bone cement distribution and injection volume, resulting in better clinical efficacy in patients with OVCF.

Evidence for adaptive myelination of subcortical shortcuts for visual motion perception in healthy adults.

Conscious visual motion information follows a cortical pathway from the retina to the lateral geniculate nucleus (LGN) and on to the primary visual cortex (V1) before arriving at the middle temporal visual area (MT/V5). Alternative subcortical pathways that bypass V1 are thought to convey unconscious visual information. One flows from the retina to the pulvinar (PUL) and on to medial temporal visual area (MT); while the other directly connects the LGN to MT. Evidence for these pathways comes from non-human primates and modest-sized studies in humans with brain lesions. Thus, the aim of the current study was to reconstruct these pathways in a large sample of neurotypical individuals and to determine the degree to which these pathways are myelinated, suggesting information flow is rapid. We used the publicly available 7T (N = 98; 'discovery') and 3T (N = 381; 'validation') diffusion magnetic resonance imaging datasets from the Human Connectome Project to reconstruct the PUL-MT (including all subcompartments of the PUL) and LGN-MT pathways. We found more fibre tracts with greater density in the left hemisphere. Although the left PUL-MT path was denser, the bilateral LGN-MT tracts were more heavily myelinated, suggesting faster signal transduction. We suggest that this apparent discrepancy may be due to 'adaptive myelination' caused by more frequent use of the LGN-MT pathway that leads to greater myelination and faster overall signal transmission.

Arithmetic Optimization AOMDV Routing Protocol for FANETs.

Flying ad hoc networks (FANETs), composed of small unmanned aerial vehicles (UAVs), possess characteristics of flexibility, cost-effectiveness, and rapid deployment, rendering them highly attractive for a wide range of civilian and military applications. FANETs are special mobile ad hoc networks (MANETs), FANETs have the characteristics of faster network topology changes and limited energy. Existing reactive routing protocols are unsuitable for the highly dynamic and limited energy of FANETs. For the lithium battery-powered UAV, flight endurance lasts from half an hour to two hours. The fast-moving UAV not only affects the packet delivery rate, average throughput, and end-to-end delay but also shortens the flight endurance. Therefore, research is urgently needed into a high-performance routing protocol with high energy efficiency. In this paper, we propose a novel routing protocol called AO-AOMDV, which utilizes arithmetic optimization (AO) to enhance the ad hoc on-demand multi-path distance vector (AOMDV) routing protocol. The AO-AOMDV utilizes a fitness function to calculate the fitness value of multiple paths and employs arithmetic optimization for selecting the optimal route for routing selection. Our experiments were conducted using NS3 with three evaluation metrics: the packet delivery ratio, network lifetime, and average end-to-end delay. We compare this algorithm to routing protocols including AOMDV and AODV. The results indicate that the proposed AO-AOMDV attained a higher packet delivery ratio, network lifetime, and lower average end-to-end delay.

SNHG1/miR-556-5p/TCF12 feedback loop enhances the tumorigenesis of meningioma through Wnt signaling pathway.

Meningioma, as a sort of the malignantly intracranial tumors, has captured public attention for its second-highest morbidity all over the world. Long noncoding RNAs (lncRNAs), including lncRNA SNHG1, have been well known as essential players in the development of diverse cancers. However, the biological effect and regulatory mechanism of SNHG1 have not been mentioned in meningioma. In this work, it was discovered that SNHG1 was overexpressed in meningioma cell lines. SNHG1 deficiency restrained cell growth as well as accelerated apoptosis. Then mechanism experiments demonstrated that SNHG1 functioned as the role of sponging miR-556-5p and negatively regulated miR-556-5p expression. Moreover, it was verified that TCF12 is the direct downstream target of miR-556-5p. Furthermore, SNHG1/miR-556-5p/TCF12 axis promoted cell proliferation and suppressed cell apoptosis in meningioma via activating the Wnt signaling pathway. In the end, it was confirmed that TCF12 expression was positively regulated by SNHG1, and TCF12 could promote transcription of SNHG1 through binding with the promoter region of SNHG1. In conclusion, the SNHG1/miR-556-5p/TCF12 feedback loop promotes the tumorigenesis of meningioma through the Wnt signaling pathway.

Gut microbiome interventions in human health and diseases.

Ongoing studies have determined that the gut microbiota is a major factor influencing both health and disease. Host genetic factors and environmental factors contribute to differences in gut microbiota composition and function. Intestinal dysbiosis is a cause or a contributory cause for diseases in multiple body systems, ranging from the digestive system to the immune, cardiovascular, respiratory, and even nervous system. Investigation of pathogenesis has identified specific species or strains, bacterial genes, and metabolites that play roles in certain diseases and represent potential drug targets. As research progresses, gut microbiome-based diagnosis and therapy are proposed and applied, which might lead to considerable progress in precision medicine. We further discuss the limitations of current studies and potential solutions.

Carbon dots synthesized by the m-trihydroxybenzene as the carbon source and its application on the detection of pH value.

New carbon dots (CDs) were prepared by a microwave method using m-trihydroxybenzene and dilute sulphuric acid as raw materials. The as-prepared CDs exhibited excellent water solubility and photoluminesence properties. The optimum excitation and emission wavelengths of the new CDs were at 365 nm and 465 nm, respectively. The fluorescence of the new CDs experienced remarkable changes in the presence of Britton-Robinson (BR) buffer solution with different pH values under 4°C after reacting for 70 min. In addition, a linear relationship between the logarithm of the relative fluorescence intensity ratio [lg(IF /IFo )] of CDs and the pH values of the sensing system ranging 1.81-5.72 was obtained, with a correlation coefficient of 0.9933. Thus, a sensitive and simple method to detect the pH value of solution was developed. Furthermore, the analytical application of detecting the concentration of acetic acid in vinegar was investigated. The detection values were found similar to the reference values, fully demonstrating a good linear relationship between the logarithm of the relative fluorescence intensity ratio of the CDs and the pH value of the system. Hence, the method could be used to detect the concentration of acetic acid in vinegar.

Application of Antioxidant Compounds in Bone Defect Repair.

Bone defects caused by trauma, tumor resection, and infections are significant clinical challenges. Excessive reactive oxygen species (ROS) usually accumulate in the defect area, which may impair the function of cells involved in bone formation, posing a serious challenge for bone repair. Due to the potent ROS scavenging ability, as well as potential anti-inflammatory and immunomodulatory activities, antioxidants play an indispensable role in the maintenance and protection of bone health and have gained increasing attention in recent years. This narrative review aims to give an overview of the main research directions on the application of antioxidant compounds in bone defect repair over the past decade. In addition, the positive effects of various antioxidants and their biomaterial delivery systems in bone repair are summarized to provide new insights for exploring antioxidant-based strategies for bone defect repair.

Preparation and evaluation of the PD0721­DOX antibody­drug conjugate targeting EGFRvIII to inhibit glioblastoma.

Epidermal growth factor receptor variant III (EGFRvIII) is prominently expressed in various epithelial tumors. PD0721, a single-chain antibody (scFv), has been developed to specifically target EGFRvIII. Although doxorubicin (DOX) is an essential treatment approach for glioblastoma (GBM), its toxic effects and limited targeting capabilities are a challenge. To overcome the above limitations, antibody-drug conjugates (ADCs) have been developed to exploit the specificity of monoclonal antibodies in directing potent cytotoxic drugs to tumor cells expressing the target antigens. The present study aimed to conjugate DOX with PD0721 scFv to construct a PD0721-DOX ADC targeting EGFRvIII and examine its targeting effect and in vitro anti-GBM activity. PD0721-DOX ADC was generated by combining PD0721 scFv with DOX, using dextran T-10 as a linker. The drug-to-antibody ratio (DAR) was measured by ultraviolet and visible spectrophotometry (UV-Vis). A series of techniques, including cytotoxicity assays, immunofluorescence, cell internalization and flow cytometry assays were employed to evaluate the targeting efficacy and anti-GBM activity of the PD0721-DOX ADC. Following the conjugation of PD0721 scFv with DOX, the UV-Vis results showed a noticeable red shift in the maximum absorbance. The DAR of PD0721 scFv and DOX was 9.23:1. Cytotoxicity assays demonstrated that DK-MG cells treatment with PD0721-DOX ADC at 10 and 20 µg/ml significantly increased cytotoxicity compared with U-87MG ATCC cells (all P<0.01). Confocal microscopy revealed distinct green and red fluorescence in EGFRvIII-expressing DK-MG cells, while no fluorescence was observed in EGFRvIII negative U-87MG ATCC cells. Furthermore, compared with U-87MG ATCC cells, DK-MG cells showed effective internalization of the PD0721-DOX ADC (P<0.001). Finally, flow cytometric analyses indicated that the PD0721-DOX ADC significantly promoted the apoptosis of DK-MG cells compared with U-87MG ATCC cells (P<0.01). In summary, the current study suggested that the PD0721-DOX ADC could exhibit a notable targeting efficacy and potent anti-GBM activity.

Near-infrared hemicyanine photosensitizer for targeted mitochondrial viscosity imaging and efficient photodynamic therapy.

As a severe threat to human health, cancer has always been one of the most significant challenges facing the medical field. However, there is currently no effective technology or method to diagnose and treat cancer simultaneously. Therefore, developing a new approach that integrates diagnosis and treatment holds promise as a means of achieving personalized and precise cancer therapy. In this study, we developed a novel dual-functional near-infrared mitochondrial-targeted photosensitizer, Hcy-I, which is capable of simultaneously monitoring cellular viscosity and specifically targeting mitochondria for photodynamic therapy. Compared with traditional hemicyanine dyes, the introduction of iodine atoms in Hcy-I enhanced spin-orbit coupling (SOC) and promoted the intersystem crossing (ISC) rate, thereby increasing the efficiency of singlet oxygen (1O2) generation. In vitro experiments demonstrated that Hcy-I exhibited high sensitivity to viscosity variations and efficiently generated 1O2 under 638 nm laser irradiation, with an 1O2 quantum yield of up to 48.9 %. Cell experiments further revealed that this photosensitizer could effectively target mitochondria for photodynamic therapy, disrupting mitochondrial membrane potential and inducing cell death. When treated with Hcy-I at a concentration of 0.8 µM, the survival rate of HepG-2 cells was only 13 %. These results suggested that Hcy-I had the potential to integrate cancer diagnosis and treatment. The research not only promotes the development of photodynamic thereby technology, but also opens up new avenues for the diagnosis and treatment of cancer.

An explanation of the role of pyroptosis playing in epilepsy.

Epilepsy is a severe central nervous system disorder characterized by an imbalance between neuronal excitation and inhibition, resulting in heightened neuronal excitability, particularly within the hippocampus. About one-third of individuals with epilepsy experience difficult-to-manage seizures, known as refractory epilepsy. Epilepsy is closely linked to inflammatory immune response, with elevated levels of inflammatory mediators observed in individuals with this condition. This inflammation of the brain can lead to seizures of various types and is further exacerbated by the release of inflammatory factors, which heighten the excitability of peripheral neurons and worsen the progression of epilepsy. Pyroptosis is an inflammatory programmed cell death which has been shown to be involved in the pathological process of epilepsy. Inflammatory factors released during pyroptosis increase neuronal excitability and promote abnormal discharge in epilepsy, increasing susceptibility to epilepsy. This article provides an overview of the current knowledge on cell pyroptosis and its potential mechanisms, including both canonical and noncanonical pathways. Additionally, we discuss the potential mechanisms of pyroptosis occurrence in epilepsy and the potential therapeutic drugs targeting pyroptosis as a treatment strategy. In summary, this review highlights the promising potential of pyroptosis as a target for developing innovative therapies for epilepsy.

Diagnostic performance of machine learning in systemic infection following percutaneous nephrolithotomy and identification of associated risk factors.

Objective: This study aims to investigate the predictive performance of machine learning in predicting the occurrence of systemic inflammatory response syndrome (SIRS) and urosepsis after percutaneous nephrolithotomy (PCNL). Methods: A retrospective analysis was conducted on patients who underwent PCNL treatment between January 2016 and July 2022. Machine learning techniques were employed to establish and select the best predictive model for postoperative systemic infection. The feasibility of using relevant risk factors as predictive markers was explored through interpretability with Machine Learning. Results: A total of 1067 PCNL patients were included in this study, with 111 (10.4 %) patients developing SIRS and 49 (4.5 %) patients developing urosepsis. In the validation set, the risk model based on the GBM protocol demonstrated a predictive power of 0.871 for SIRS and 0.854 for urosepsis. Preoperative and postoperative platelet changes were identified as the most significant predictors. Both thrombocytopenia and thrombocytosis were found to be risk factors for SIRS or urosepsis after PCNL. Furthermore, it was observed that when the change in platelet count before and after PCNL surgery exceeded 30*109/L (whether an increase or decrease), the risk of developing SIRS or urosepsis significantly increased. Conclusion: Machine learning can be effectively utilized for predicting the occurrence of SIRS or urosepsis after PCNL. The changes in platelet count before and after PCNL surgery serve as important predictors.

The Effect of Asymmetrical Occlusion on Surface Electromyographic Activity in Subjects with a Chewing Side Preference: A Preliminary Study.

The relationship between asymmetrical occlusion and surface electromyographic activity (sEMG) in people with different chewing preferences is not clear. In this study, the 5 s sEMG changes in the masseter muscle (MM), sternocleidomastoid (SCM), lateral (LGA), and medial (MGA) gastrocnemius muscles were recorded in controls, and subjects with chewing side preference (CSP) during clench with bilateral (BCR), left (LCR), and right (RCR) posterior teeth placement of cotton rolls. The images of the middle 3 s were selected and expressed as the root mean square (unit: µV/s). The EMG waves of bilateral muscles were compared by computing the percentage overlapping coefficient (POC). Only the POCMM of the CSP showed gender differences at BCR and RCR. Between the control group and the CSP group, there were significant differences in the POCMM and the POCLGA at BCR. In addition, there was a significant difference in POCMM and POCSCM between the two populations in different occlusal positions. The change in the POCSCM correlated with the change in the POCMM (r = 0.415, p = 0.018). The experiment-induced asymmetrical occlusion showed that the altered symmetry of the MM correlated with the altered symmetry of the SCM. Long-term asymmetrical occlusion (i.e., CSP) not only affects MM but also has potential effects on other superficial muscles (e.g., LGA).

In situ synthesis of two-dimensional graphene-like nickel-molybdenum nitride as efficient electrocatalyst towards water-splitting under large-current density.

Transition metal nitride (TMNs) electrocatalysts have attracted tremendous attentions for their unique electron structure, high activity, and excellent stability. Herein, a two-dimensional (2D) graphene-like structured nickel-molybdenum nitride (Ni-MoN) on nickel foam (NF), is prepared via facile hydrothermal and following nitridation process. The as-prepared Ni-MoN-450 (pyrolysis at 450 °C) displays good hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) performances in alkaline media. Only 22 mV and 117 mV are needed to achieve current densities of 10 mA cm-2 and 500 mA cm-2 in 1.0 M KOH, respectively, toward HER. The assembled two-electrode system, with the synthesized Ni-MoN-450 as the anode and cathode, exhibits good performance to achieve 1000 mA cm-2 in 1.0 M KOH + 25 °C and 6.0 M KOH + 80 °C. Moreover, it also presents long-term stability under large-current density, which verified its robust property.

Extensible carbon emission factor database: empirical study for the Chinese construction industry.

A carbon emission factor (CEF) database is required for the basis of carbon emission calculation in construction projects. However, the default values for existing CEF databases cannot cover the complex resources involved in a construction project. Therefore, this paper proposes a three-step method to guide the establishment of an extensible CEF database for the construction industry, including (1) data collection and parser, (2) data extension, and (3) data encoding and storage. The data extension mechanisms provide the supply chain perspective considering temporal issues and the accounting perspective to streamline the process. Aiming to address the lack of a comprehensive CEF database for the construction industry in China, this paper uses this method to establish a carbon emission factor database for the Chinese construction industry (CEFD for CCI). This database is open and free with 646 CEFs, including five parts: energy, human, material, machinery, and greenspace. This paper provides a way for developing and less developed countries to establish an expandable CEF database, which benefits the parser, extension, encoding, and storage of new resources, as well as computer access.

Ultrasmall RuM (Mo, W, Cr) Decorated on Nitrogen-doped Carbon Nanosheet with Strong Metal-support Interactions for Electrocatalytic Hydrogen Generation in Wide pH Range.

Developing efficient electrocatalysts for hydrogen evolution reaction (HER) in full pH range can promote the practical applications of hydrogen energy. In this work, nitrogen doped carbon nanosheets supported RuM (Mo, W, Cr) (RuM/NCN) are prepared through an ultrafast microwave approach. The carbon nanosheet structure coupled with the ultrasmall RuM nanoparticles can expose rich active sites to optimize the catalytic activity. Moreover, the strong metal-support interactions also favor to accelerate the reactions kinetics and improve stability. Thus, the developed RuMo/NCN (RuW/NCN) show excellent HER catalytic activities with overpotentials of 72 (75) mV, 82 (82) mV and 124 (119) mV to reach current density of 10 mA cm -2 in 1 M KOH, 0.5 M H2SO4 and alkaline seawater, respectively, and also achieve excellent performance in 1 M PBS. This work provides a valid and novel avenue to design efficient electrocatalysts in renewable energy-related fields.

Discovery of an OTUD3 inhibitor for the treatment of non-small cell lung cancer.

The ubiquitin-proteasome system (UPS) controls protein turnover, and its dysfunction contributes to human diseases including cancer. Deubiquitinating enzymes (DUBs) remove ubiquitin from proteins to maintain their stability. Inhibition of DUBs could induce the degradation of selected oncoproteins and has therefore become a potential therapeutic strategy for cancer. The deubiquitylase OTUD3 was reported to promote lung tumorigenesis by stabilizing oncoprotein GRP78, implying that inhibition of OTUD3 may be a therapeutic strategy for lung cancer. Here, we report a small-molecule inhibitor of OTUD3 (named OTUDin3) by computer-aided virtual screening and biological experimental verification. OTUDin3 exhibited pronounced antiproliferative and proapoptotic effects by inhibiting deubiquitinating activity of OTUD3 in non-small-cell lung cancer (NSCLC) cell lines. Moreover, OTUDin3 efficaciously inhibited growth of lung cancer xenografts in mice. In summary, our results support OTUDin3 as a potent inhibitor of OTUD3, the inhibition of which may be a promising therapeutic strategy for NSCLC.

Rosmarinic acid alleviates diabetic osteoporosis by suppressing the activation of NLRP3 inflammasome in rats.

BACKGROUND: Diabetic osteoporosis is a common metabolic bone disorder characterized by bone loss in diabetic patients, which causes an enormous social burden due to the unsatisfactory outcome of current therapeutic strategy. METHODS: Based on the importance of inflammasome activation in diabetic osteoporosis, we evaluated the protective effect of an antioxidant, rosmarinic acid (RA) in diabetic osteoporosis. Bone marrow-derived monocytes isolated from rats were treated with receptor activator of nuclear factor kappa-Β ligand (RANKL) and macrophage colony stimulating factor to differentiate into mature osteoclasts (OCs). Next OCs were stimulated with RA under high glucose condition to evaluate bone resorption. Next, streptozotocin (STZ)-injected rats were orally treated with 50 mg kg-1 RA to analyze its effect on diabetic osteoporosis. RESULTS: RA inhibited high glucose-stimulated inflammation and inflammasome activation in OCs. Bone resorption was also reduced after RA treatment as shown by the resorption pits assay. Moreover, RA significantly reduced bone resorption, alleviated bone weight loss and increased bone mineral density by inhibiting the activation of NACHT-LRR-PYD domains-containing protein 3 (NLRP3) inflammasome in STZ-induced diabetic rats, leading to the improvement of diabetic osteoporosis. CONCLUSION: RA effectively ameliorates diabetic osteoporosis in STZ-induced rats by inhibiting the activation of NLRP3 inflammasome in OCs, which suggests that RA might serve as a potential candidate drug for treating diabetic osteoporosis.

Alginate Oligosaccharide Alleviated Cisplatin-Induced Kidney Oxidative Stress via Lactobacillus Genus-FAHFAs-Nrf2 Axis in Mice.

Alginate oligosaccharide is the depolymerized product of alginate, a natural extract of brown algae, which is associated with beneficial health effects. Here, we aimed to investigate the mechanism via which alginate oligosaccharides improve kidney oxidative damage and liver inflammation induced by cisplatin chemotherapy via the gut microbiota. C57BL/6J mice were treated with cisplatin were administered alginate oligosaccharide via gavage for 3 weeks. Compared to that observed in the cisplatin chemotherapy group without intragastric administration of alginate oligosaccharide, liver inflammation improved in the alginate oligosaccharide group, indicated by reduction in lipopolysaccharide and interleukin-1ß (IL-1ß) levels. This was accompanied by improvement in the oxidative stress of mice kidneys, indicated by the increase in the levels of superoxide dismutase (SOD), catalase (CAT) and nuclear NF-E2-related factor 2 (Nrf2) in renal tissue, and reduction in the levels of malondialdehyde (MDA) in renal tissue and serum creatinine (Cr) to the levels of the normal control group. Alginate oligosaccharide intervention increased the concentration of fatty acid esters of hydroxy fatty acids (FAHFAs). Alginate oligosaccharide regulated the composition of the intestinal microbial community and promoted Lactobacillus stains, such as Lactobacillus johnsonii and Lactobacillus reuteri. Spearman analysis showed that 5 members of FAHFAs concentrations were positively correlated with Lactobacillus johnsonii and Lactobacillus reuteri abundance. We observed that alginate oligosaccharide increased FAHFAs producing-related bacterial abundance and FAHFAs levels, enhanced the levels of SOD and CAT in kidney tissue, and reduced the levels of MDA via activating Nrf2, thereby ameliorating the renal redox injury caused by cisplatin chemotherapy.

C-phycocyanin alleviated cisplatin-induced oxidative stress and inflammation via gut microbiota-metabolites axis in mice.

C-phycocyanin is a natural protein extracted from Spirulina platensis. We aim to investigate the preventive effect of C-phycocyanin on cisplatin chemotherapy-induced oxidative damage and inflammation. The result showed that C-phycocyanin treatment reduced cisplatin-induced mortality and inflammation including decreased levels of serum IL6, kidney MCP1, and liver IL1ß. Furthermore, C-phycocyanin also exerted antioxidant effects on mice, including increased GSH-Px, GGT, and GSH levels in the liver and increased CAT and SOD levels in the kidney. HepG2 cells experiments showed that C-phycocyanin exhibited none of the prevention effects on cisplatin injury. Faecalibaculum showed the greatest reduction among genera after cisplatin treatment, which was related to the enrichment of Romboutsia and Lactobacillus genera. C-phycocyanin treatment reduced the populations of harmful bacteria of Enterococcus faecalis, which was positively correlated with inflammation induced by cisplatin. C-phycocyanin increased the contents of 23-nordeoxycholic acid and ß-muricholic acid. Moreover, C-phycocyanin increased amino acid-related metabolites, Nα-acetyl-arginine and trimethyl-lysine contents, and decreased fatty acid esters of hydroxy fatty acids (FAHFAs) contents. In conclusion, C-phycocyanin inhibited inflammation via the 23-nordeoxycholic acid-Enterococcus faecalis-inflammation axis, and enhanced the antioxidant capacity of kidney via Lactobacillus-NRF2 pathway. C-phycocyanin alleviated cisplatin injury via the modulation of gut microbiota, especially Lactobacillus and Enterococcus, as well as regulation of metabolites, especially bile acid and FAHFAs, which highlight the effect of C-phycocyanin and provide a new strategy to prevent cisplatin injury.