Co-inoculation of fungi and desert cyanobacteria facilitates biological soil crust formation and soil fertility.

The inoculation of cyanobacteria for enriching soil nutrients and forming biological soil crusts (BSCs) is considered an effective means to restore degraded soil. However, there are limited studies on the application of co-inoculation of fungi and cyanobacteria for degraded soil remediation. In this study, a high exopolysaccharide-secreting fungi Zh2 was isolated from lichen BSCs in Hobq Desert, and co-inoculated with a cyanobacterial strain identified as Phormidium tenue in different proportions to form BSCs on sand during a 35 days incubation period. Results revealed significant differences in crust biomass and soil properties among crusts with different cyanobacterial/fungal inoculation ratios. Microbial biomass, soil nutrient content and enzyme activities in crusts co-inoculated with cyanobacteria and fungi were higher than those inoculated with cyanobacteria and fungi alone. The inoculation of cyanobacteria contributed to the fulvic-like accumulation, and the inoculated fungi significantly increased the humic-like content and soil humification. Redundancy analysis showed that the inoculation of cyanobacteria was positively correlated with the activities of urease and phosphatase, and the content of fulvic-like. Meanwhile, the inoculation of fungi was positively correlated with the contents of total carbon, total nitrogen and humic-like, the activities of catalase and sucrase. Cyanobacteria and fungi play distinct roles in improving soil fertility and accumulating dissolved organic matter. This study provides new insights into the effects of cyanobacteria and fungi inoculations on the formation and development of cyanobacterial-fungus complex crusts, offering a novel method for accelerating induced crust formation on the surface of sand.

The SP1/SIRT1/ACLY signaling axis mediates fatty acid oxidation in renal ischemia-reperfusion-induced renal fibrosis.

BACKGROUND: Renal ischemia-reperfusion is the primary cause of acute kidney injury (AKI). Clinically, most patients who experience ischemia-reperfusion injury eventually progress gradually to renal fibrosis and chronic kidney disease (CKD). However, the underlying mechanism for AKI to CKD transition remain absent. Our study demonstrated that the downregulation of sirtuin 1 (Sirt1)-mediated fatty acid oxidation (FAO) facilitates IRI-induced renal fibrosis. METHODS: The IRI animal model was established, and ribonucleic acid (RNA) sequencing was used to explore potential differentially expressed genes (DEGs) and pathways. The SIRT1 knockout mice were generated, and a recombinant adeno-associated virus that overexpresses SIRT1 was injected into mice to explore the function of SIRT1 in renal fibrosis induced by renal IRI. In vitro, hypoxia/reoxygenation (H/R) was used to establish the classical model of renal IRI and overexpression or knockdown of SIRT1 to investigate the SIRT1 function through lentiviral plasmids. The underlying molecular mechanism was explored through RNA sequencing, bioinformatics analysis, and chromatin immunoprecipitation assay. RESULTS: RNA sequencing analysis and western blot demonstrated that the expression of SIRT1 was significantly decreased in IRI mice. Overexpression of SIRT1 improved renal function and reduced lipid deposition and renal fibrosis. On the contrary, knockout of SIRT1 aggravated kidney injury and renal fibrosis. RNA sequencing, bioinformatics analysis, and chromatin immunoprecipitation assay mechanistically revealed that SIRT1 impairs the acetylation of histone H3K27 on the promoter region of ACLY, thereby impeding FAO activity and promoting renal fibrosis. Additionally, SP1 regulated FAO by directly modulating SIRT1 expression. CONCLUSION: Our findings highlight that downregulation of SIRT1-modulated FAO facilitated by the SP1/SIRT1/ACLY axis in the kidney increases IRI, suggesting SIRT1 to be a potential therapeutic target for renal fibrosis induced by renal IRI.

Predicting the current fishable habitat distribution of Antarctic toothfish (Dissostichus mawsoni) and its shift in the future under climate change in the Southern Ocean.

Global warming continues to exert unprecedented impacts on marine habitats. Species distribution models (SDMs) are proven powerful in predicting habitat distribution for marine demersal species under climate change impacts. The Antarctic toothfish, Dissostichus mawsoni (Norman 1937), an ecologically and commercially significant species, is endemic to the Southern Ocean. Utilizing occurrence records and environmental data, we developed an ensemble model that integrates various modelling techniques. This model characterizes species-environment relationships and predicts current and future fishable habitats of D. mawsoni under four climate change scenarios. Ice thickness, depth and mean water temperature were the top three important factors in affecting the distribution of D. mawsoni. The ensemble prediction suggests an overall expansion of fishable habitats, potentially due to the limited occurrence records from fishery-dependent surveys. Future projections indicate varying degrees of fishable habitat loss in large areas of the Amery Ice Shelf's eastern and western portions. Suitable fishable habitats, including the spawning grounds in the seamounts around the northern Ross Sea and the coastal waters of the Bellingshausen Sea and Amundsen Sea, were persistent under present and future environmental conditions, highlighting the importance to protect these climate refugia from anthropogenic disturbance. Though data deficiency existed in this study, our predictions can provide valuable information for designing climate-adaptive development and conservation strategies in maintaining the sustainability of this species.

HLA-class II restricted TCR targeting human papillomavirus type 18 E7 induces solid tumor remission in mice.

T cell receptor (TCR)-engineered T cell therapy is a promising potential treatment for solid tumors, with preliminary efficacy demonstrated in clinical trials. However, obtaining clinically effective TCR molecules remains a major challenge. We have developed a strategy for cloning tumor-specific TCRs from long-term surviving patients who have responded to immunotherapy. Here, we report the identification of a TCR (10F04), which is human leukocyte antigen (HLA)-DRA/DRB1*09:01 restricted and human papillomavirus type 18 (HPV18) E784-98 specific, from a multiple antigens stimulating cellular therapy (MASCT) benefited metastatic cervical cancer patient. Upon transduction into human T cells, the 10F04 TCR demonstrated robust antitumor activity in both in vitro and in vivo models. Notably, the TCR effectively redirected both CD4+ and CD8+ T cells to specifically recognize tumor cells and induced multiple cytokine secretion along with durable antitumor activity and outstanding safety profiles. As a result, this TCR is currently being investigated in a phase I clinical trial for treating HPV18-positive cancers. This study provides an approach for developing safe and effective TCR-T therapies, while underscoring the potential of HLA class II-restricted TCR-T therapy as a cancer treatment.

An efficient and simple approach to remove Cd(II) in aqueous solution by using rice straw biochar: performance and mechanisms.

In recent years, cadmium pollution in water environment has become an environmental problem that could not be ignored. As a porous carbon rich solid material, biochar is an environment-friendly new material because of its ultra-high adsorption capacity and strong chemical stability. In this study, rice straw biochar (RS-Biochar) was successfully prepared at different temperatures for removal of Cd(II) from aqueous solution. Through a series of characterization and adsorption experiments, the adsorption principle of Cd(II) by RS-Biochar was deeply studied. The results showed that RS-Biochar prepared at 600 °C (BioC600) has high specific surface area (232.6 m2/g) and shows high Cd(II) removal rate of 91.23% with the maximum Cd(II) adsorption capacity of 8.62 mg/g. The Langmuir model fit well to describe the adsorption process of Cd(II) on the BioC600. The mechanism analysis showed that hydroxyl and carboxyl groups on the biochar surface were concerned in the removal of Cd(II). The formation of CdCO3 in the adsorption process was also be proven. Importantly, RS-Biochar could be conveniently produced with needed scale, displaying a promising approach for remediating Cd(II)-contaminated water environment and a huge application potential.

The SOX4/EZH2/SLC7A11 signaling axis mediates ferroptosis in calcium oxalate crystal deposition-induced kidney injury.

Epigenetic regulation is reported to play a significant role in the pathogenesis of various kidney diseases, including renal cell carcinoma, acute kidney injury, renal fibrosis, diabetic nephropathy, and lupus nephritis. However, the role of epigenetic regulation in calcium oxalate (CaOx) crystal deposition-induced kidney injury remains unclear. Our study demonstrated that the upregulation of enhancer of zeste homolog 2 (EZH2)-mediated ferroptosis facilitates CaOx-induced kidney injury. CaOx crystal deposition promoted ferroptosis in vivo and in vitro. Usage of liproxstatin-1 (Lip-1), a ferroptosis inhibitor, mitigated CaOx-induced kidney damage. Single-nucleus RNA-sequencing, RNA-sequencing, immunohistochemical and western blotting analyses revealed that EZH2 was upregulated in kidney stone patients, kidney stone mice, and oxalate-stimulated HK-2 cells. Experiments involving in vivo EZH2 knockout, in vitro EZH2 knockdown, and in vivo GSK-126 (an EZH2 inhibitor) treatment confirmed the protective effects of EZH2 inhibition on kidney injury and ferroptosis. Mechanistically, the results of RNA-sequencing and chromatin immunoprecipitation assays demonstrated that EZH2 regulates ferroptosis by suppressing solute carrier family 7, member 11 (SLC7A11) expression through trimethylation of histone H3 lysine 27 (H3K27me3) modification. Additionally, SOX4 regulated ferroptosis by directly modulating EZH2 expression. Thus, this study demonstrated that SOX4 facilitates ferroptosis in CaOx-induced kidney injury through EZH2/H3K27me3-mediated suppression of SLC7A11.

BMAL1 inhibits renal fibrosis and renal interstitial inflammation by targeting the ERK1/2/ELK-1/Egr-1 axis.

RATIONALE: Renal fibrosis and renal interstitial inflammation due to hydronephrosis are associated with progressive chronic kidney disease (CKD). The clock gene BMAL1 is thought to be involved in various diseases, including hypertension, diabetes, etc. However, little is known about how BMAL1 regulates renal fibrosis and renal interstitial inflammation in obstructed kidneys. METHODS: The expression level of BMAL1 in UUO was examined using the GEO database. Lentivirus, siRNA and adeno-associated virus were used to modulate BMAL1 levels in HK-2 cells and mouse kidney. qRT-PCR, immunofluorescence staining, histological analysis, ELISA and Western blot were used to determine the level of fibrin deposition and the release of inflammatory factors. Immunofluorescence staining and western blotting were used to examine the interaction between BMAL1 and the ERK1/2/ELK-1/Egr-1 axis. RESULTS: Bioinformatics analysis and in vivo experiments in this study showed that the expression level of BMAL1 in UUO model kidneys was higher than that in normal kidneys. We then found that downregulation of BMAL1 promoted the production of extracellular matrix (ECM) proteins and proinflammatory factors in vivo and in vitro, whereas upregulation inhibited this process. In addition, we demonstrated that the ERK1/2/ELK-1/Egr-1 axis is an important pathway for BMAL1 to play a regulatory role, and the use of PD98059 abolished the promoting effect of down-regulation of BMAL1 on fibrosis and inflammation. CONCLUSIONS: Our findings suggest that BAML1 can target the ERK1/2/ELK-1/Egr-1 axis to suppress fibrotic progression and inflammatory events in obstructed kidneys, thereby inhibiting the development of CKD.

STAT6 promoting oxalate crystal deposition-induced renal fibrosis by mediating macrophage-to-myofibroblast transition via inhibiting fatty acid oxidation.

OBJECTIVE AND DESIGN: Kidney stones commonly occur with a 50% recurrence rate within 5 years, and can elevate the risk of chronic kidney disease. Macrophage-to-myofibroblast transition (MMT) is a newly discovered mechanism that leads to progressive fibrosis in different forms of kidney disease. In this study, we aimed to investigate the role of MMT in renal fibrosis in glyoxylate-induced kidney stone mice and the mechanism by which signal transducer and activator of transcription 6 (STAT6) regulates MMT. METHODS: We collected non-functioning kidneys from patients with stones, established glyoxylate-induced calcium oxalate stone mice model and treated AS1517499 every other day in the treatment group, and constructed a STAT6-knockout RAW264.7 cell line. We first screened the enrichment pathway of the model by transcriptome sequencing; detected renal injury and fibrosis by hematoxylin eosin staining, Von Kossa staining and Sirius red staining; detected MMT levels by multiplexed immunofluorescence and flow cytometry; and verified the binding site of STAT6 at the PPARα promoter by chromatin immunoprecipitation. Fatty acid oxidation (FAO) and fibrosis-related genes were detected by western blot and real-time quantitative polymerase chain reaction. RESULTS: In this study, we found that FAO was downregulated, macrophages converted to myofibroblasts, and STAT6 expression was elevated in stone patients and glyoxylate-induced kidney stone mice. The promotion of FAO in macrophages attenuated MMT and upregulated fibrosis-related genes induced by calcium oxalate treatment. Further, inhibition of peroxisome proliferator-activated receptor-α (PPARα) eliminated the effect of STAT6 deletion on FAO and fibrosis-associated protein expression. Pharmacological inhibition of STAT6 also prevented the development of renal injury, lipid accumulation, MMT, and renal fibrosis. Mechanistically, STAT6 transcriptionally represses PPARα and FAO through cis-inducible elements located in the promoter region of the gene, thereby promoting MMT and renal fibrosis. CONCLUSIONS: These findings establish a role for STAT6 in kidney stone injury-induced renal fibrosis, and suggest that STAT6 may be a therapeutic target for progressive renal fibrosis in patients with nephrolithiasis.

YAP/ACSL4 Pathway-Mediated Ferroptosis Promotes Renal Fibrosis in the Presence of Kidney Stones.

The potential association between calcium oxalate stones and renal fibrosis has been extensively investigated; however, the underlying mechanisms remain unclear. Ferroptosis is a novel form of cell death characterized by iron-dependent lipid peroxidation and regulated by acyl coenzyme A synthase long-chain family member 4 (ACSL4). Yes-associated protein (YAP), a transcriptional co-activator in the Hippo pathway, promotes ferroptosis by modulating ACSL4 expression. Nevertheless, the involvement of YAP-ACSL4 axis-mediated ferroptosis in calcium oxalate crystal deposition-induced renal fibrosis and its molecular mechanisms have not been elucidated. In this study, we investigated ACSL4 expression and ferroptosis activation in the kidney tissues of patients with calcium oxalate stones and in mice using single-cell sequencing, transcriptome RNA sequencing, immunohistochemical analysis, and Western blot analysis. In vivo and in vitro experiments demonstrated that inhibiting ferroptosis or ACSL4 mitigated calcium oxalate crystal-induced renal fibrosis. Furthermore, YAP expression was elevated in the kidney tissues of patients with calcium oxalate stones and in calcium oxalate crystal-stimulated human renal tubular epithelial cell lines. Mechanistically, in calcium oxalate crystal-stimulated human renal tubular epithelial cell lines, activated YAP translocated to the nucleus and enhanced ACSL4 expression, consequently inducing cellular ferroptosis. Moreover, YAP silencing suppressed ferroptosis by downregulating ACSL4 expression, thereby attenuating calcium oxalate crystal-induced renal fibrosis. Conclusively, our findings suggest that YAP-ACSL4-mediated ferroptosis represents an important mechanism underlying the induction of renal fibrosis by calcium oxalate crystal deposition. Targeting the YAP-ACSL4 axis and ferroptosis may therefore hold promise as a potential therapeutic approach for preventing renal fibrosis in patients with kidney stones.

Comprehensive analysis reveals XCL2 as a cancer prognosis and immune infiltration-related biomarker.

BACKGROUND: X-C Motif Chemokine Ligand 2 (XCL2) is a 114 amino acid, structurally conserved chemokine involved in activating cytotoxic T cells. However, the pathophysiological mechanisms of XCL2 protein in various disease conditions, particularly cancer, remain poorly understood. METHODS: Bioinformatics was used to detect the expression of XCL2, the relationship between survival time and XCL2 in BLCA patients, the mutational status of XCL2, the role of XCL2 in the tumor immune microenvironment, and the sensitivity of XCL2-targeted drugs in 33 cancers. In vitro experiments were conducted to investigate the chemotactic effects of XCL2 expression on M1-type macrophages in human specimens and in isolated cancer cells. RESULTS: XCL2 expression was downregulated in tumor tissues and closely associated with the prognosis of human cancers. Furthermore, XCL2 affects DNA methylation, tumor mutation burden (TMB), microsatellite instability (MSI), and mismatch repair (MMR) in human cancers. The expression level of XCL2 significantly correlated with infiltrated immune cells, immunological pathways, and other immune markers. More importantly, we found that XCL2 was positively associated with T lymphocytes and macrophages in the transcriptome and single-cell sequencing data. Using multiple immunofluorescence staining, we found that the expression level of XCL2 was upregulated in many cells in pan-cancer samples, and the number of M1 macrophage marker CD68 and INOS-positive cells increased. 786O, U251, and MDA-MB-231 cells could recruit more M1 macrophages in vitro after overexpressing XCL2. CONCLUSIONS: Our results reveal that XCL2 could act as a vital chemokine in pan-cancer and provide new targets and concepts for cancer treatment.

Centralized health management based on hot spring resort improves physical examination indicators and sleep quality in people at high risk of chronic diseases: a randomized controlled trial.

We study the effects of centralized health management based on hot spring resorts on the physical examination index and sleep quality of people at high risk of chronic diseases. We recruited 114 volunteers at high risk of chronic diseases. We then divided them into 57 in the intervention group and 57 in the control group. The intervention group collectively received 4 weeks (28 days) of comprehensive health management interventions at Tongjing Hotspring Resort, including regular schedules, balanced diet, appropriate exercise, targeted health education, etc. The main outcomes are physical examination indicators (height, weight, waist circumference, blood pressure, lipids, and glucose) and sleep quality. Both groups underwent a questionnaire and physical examination at baseline, 2 weeks and 4 weeks. Intragroup comparisons grouped by exposure criteria showed decreases in BMI, waist circumference, triglycerides, total cholesterol, and blood glucose in the intervention group at both 2 and 4 weeks (all P < 0.05); however, in the control group, only triglycerides decreased at 4 weeks (P < 0.05). Intergroup comparisons showed BMI and waist circumference were significantly lower in the intervention group than in the control group at 4 weeks (all P < 0.05). Intragroup comparisons of insomnia severity index (ISI) scores showed a significant decrease in the intervention group at both 2 and 4 weeks (all P < 0.001) with no significant change in the control group (P > 0.05). Intergroup comparisons showed that the insomnia severity index (ISI) scores were significantly higher in the intervention group than in the control group at baseline (P = 0.006) but became significantly lower than the control group at 2 and 4 weeks (all P < 0.001). Thus, this pattern significantly improved BMI, waist circumference, triglycerides, and sleep in the intervention group. TRIAL REGISTRATION NUMBER: Chinese Clinical Trials Registry: ChiCTR2100053201, registered 14 Nov 2021. (Retroactive Registration).

RAE1 promotes nitrosamine-induced malignant transformation of human esophageal epithelial cells through PPARα-mediated lipid metabolism.

Esophageal cancer (EC) is the sixth cause of cancer-related deaths and still is a significant public health problem globally. Nitrosamines exposure represents a major health concern increasing EC risks. Exploring the mechanisms induced by nitrosamines may contribute to the prevention and early detection of EC. However, the mechanism of nitrosamine carcinogenesis remains unclear. Ribonucleic acid export 1 (RAE1), has an important role in mediating diverse cancer types, but, to date, there has been no study for any functional role of RAE1 in esophageal carcinogenesis. Here, we successfully verified the nitrosamine-induced malignant transformation cell (MNNG-M) by xenograft tumor model, based on which it was found that RAE1 was upregulation in the early stage of nitrosamine-induced esophageal carcinogenesis and EC tissues. RAE1 knockdown led to severe blockade in G2/M phase and significant inhibition of proliferation of MNNG-M cells, whereas RAE1 overexpression had the opposite effect. In addition, peroxisome proliferator-activated receptor-alpha (PPARα), was demonstrated as a downstream target gene of RAE1, and its down-regulation reduced lipid accumulation, resulting in causing cells accumulation in the G2/M phase. Mechanistically, we found that RAE1 regulates the lipid metabolism by maintaining the stability of PPARα mRNA. Taken together, our study reveals that RAE1 promotes malignant transformation of human esophageal epithelial cells (Het-1A) by regulating PPARα-mediated lipid metabolism to affect cell cycle progression, and offers a new explanation of the mechanisms underlying esophageal carcinogenesis.

Prognostic and immunological roles of IL18RAP in human cancers.

Across several cancers, IL18 receptor accessory protein (IL18RAP) is abnormally expressed, and this abnormality is related to tumor immunity and heterogeneous clinical outcomes. In this study, based on bioinformatics analysis, we discovered that IL18RAP is related to the human tumor microenvironment and promotes various immune cells infiltration. Additionally, the multiple immunofluorescence staining revealed that with the increased expression of IL18RAP, the number of infiltrated M1 macrophages increased. This finding was confirmed by coculture migration analysis using three human cancer cell lines (MDA-MB-231, U251, and HepG2) with IL18RAP knockdown. We discovered a positive link between IL18RAP and the majority of immunostimulators, immunoinhibitors, major histocompatibility complex (MHC) molecules, chemokines, and chemokine receptor genes using Spearman correlation analysis. Additionally, functional IL18RAP's gene set enrichment analysis (GSEA) revealed that it is related to a variety of immunological processes, such as positive regulation of interferon gamma production and positive regulation of NK cell-mediated immunity. Moreover, we used single-cell RNA sequencing analysis to detect that IL18RAP was mainly expressed in immune cells, and HALLMARK analysis confirmed that the INF-γ gene set expression was upregulated in CD8Tex cells. In addition, in human and mouse cancer cohorts, we found that the level of IL18RAP can predict the immunotherapy response. In short, our study showed that IL18RAP is a new tumor biomarker and may become a potential immunotherapeutic target in cancer.

Classification and clinical significance of the posterior group of renal calyces.

To study the anatomical orientation of the posterior group of calyces based on reconstructed images of computerized tomography urography (CTU) and provide a novel classification with its clinical significance. Clinical data of a total of 1321 patients, who underwent CTU examination in our hospital were retrospectively analyzed. Among these, a total of 2642 3-dimensional reconstructed images of CTU scans were considered in this study. Based on the morphology of the renal calyces and the influence on the establishment of surgical access, the posterior group renal calyces are classified into 3 major types including pot-belly type, classically branched and elongated branched. The classically branched type is further classified into 3 sub-types: a, b and c, based on the association of minor calyces of the posterior group to the major calyces. Type a is derived from 1 group of major calyces only, type b is derived from 2 groups of major calyces simultaneously, and type c is derived from 3 groups of major calyces simultaneously. Statistical findings revealed that all kidneys possess posterior group calyces. The percentage of occurrence of pot-belly type, classically branched and elongated branched is 8.06%, 73.13%, and 18.81%, respectively. The anatomical typing of the classical branching type occurred in 19.36%, 68.17%, and 12.47% for types a, b, and c, respectively. In this study, the posterior group calyces were found to be present across all patients. The posterior group calyces were highest in the classical branching type, of which anatomical typing was highest in type b. The typing of the posterior group of calyces could provide an anatomical basis for percutaneous nephrolithotomy (PCNL) puncture from the posterior group.

Successful anesthesia management with inhalation anesthesia in Rosai-Dorfman disease: a case report.

Rosai-Dorfman disease (RDD) is a rare, benign, non-Langerhans cell histiocytic proliferative disease. RDD with central nervous system involvement is extremely rare. Surgical excision is generally regarded as the appropriate treatment of choice for this disease, especially when the lesion causes neurological compression. RDD can be accompanied by systemic symptoms, such as malaise, fever, weight change, leukocytosis, anemia, and hormonal disturbance, which may be challenging during general management. Little is known regarding peri-anesthesia management of this rare disease. We report a case of a patient in his 20s who had recurrent RDD and had general anesthesia with perioperative management. He was obese and hepatic insufficiency. This case report adds to the literature regarding the perioperative anesthetic management of RDD with central nervous system involvement.

Liang-Ge-San: a classic traditional Chinese medicine formula, attenuates acute inflammation via targeting GSK3ß.

Sepsis is a serious life-threatening health disorder with high morbidity and mortality rates that burden the world, but there is still a lack of more effective and reliable drug treatment. Liang-Ge-San (LGS) has been shown to have anti-inflammatory effects and is a promising candidate for the treatment of sepsis. However, the anti-sepsis mechanism of LGS has still not been elucidated. In this study, a set of genes related to inflammatory chemotaxis pathways was downloaded from Encyclopedia of Genes and Genomes (KEGG) and integrated with sepsis patient information from the Gene Expression Omnibus (GEO) database to perform differential gene expression analysis. Glycogen synthase kinase-3ß (GSK-3ß) was found to be the feature gene after these important genes were examined using the three algorithms Random Forest, support vector machine recursive feature elimination (SVM-REF), and least absolute shrinkage and selection operator (LASSO), and then intersected with possible treatment targets of LGS found through the search. Upon evaluation, the receiver operating characteristic (ROC) curve of GSK-3ß indicated an important role in the pathogenesis of sepsis. Immune cell infiltration analysis suggested that GSK-3ß expression was associated with a variety of immune cells, including neutrophils and monocytes. Next, lipopolysaccharide (LPS)-induced zebrafish inflammation model and macrophage inflammation model was used to validate the mechanism of LGS. We found that LGS could protect zebrafish against a lethal challenge with LPS by down-regulating GSK-3ß mRNA expression in a dose-dependent manner, as indicated by a decreased neutrophils infiltration and reduction of inflammatory damage. The upregulated mRNA expression of GSK-3ß in LPS-induced stimulated RAW 264.7 cells also showed the same tendency of depression by LGS. Critically, LGS could induce M1 macrophage polarization to M2 through promoting GSK-3ß inactivation of phosphorylation. Taken together, we initially showed that anti-septic effects of LGS is related to the inhibition on GSK-3ß, both in vitro and in vivo.

Overexpression of sirtuin 1 attenuates calcium oxalate-induced kidney injury by promoting macrophage polarization.

Sirtuin 1 (SIRT1) protein is involved in macrophage differentiation, while NOTCH signaling affects inflammation and macrophage polarization. Inflammation and macrophage infiltration are typical processes that accompany kidney stone formation. However, the role and mechanism of SIRT1 in renal tubular epithelial cell injury caused by calcium oxalate (CaOx) deposition and the relationship between SIRT1 and the NOTCH signaling pathway in this urological disorder are unclear. This study investigated whether SIRT1 promotes macrophage polarization to inhibit CaOx crystal deposition and reduce renal tubular epithelial cell injury. Public single-cell sequencing data, RT-qPCR, immunostaining approaches, and Western blotting showed decreased SIRT1 expression in macrophages treated with CaOx or exposed to kidney stones. Macrophages overexpressing SIRT1 differentiated towards the anti-inflammatory M2 phenotype, significantly inhibiting apoptosis and alleviating injury in the kidneys of mice with hyperoxaluria. Conversely, decreased SIRT1 expression in CaOx-treated macrophages triggered Notch signaling pathway activation, promoting macrophage polarization towards the pro-inflammatory M1 phenotype. Our results suggest that SIRT1 promotes macrophage polarization towards the M2 phenotype by repressing the NOTCH signaling pathway, which reduces CaOx crystal deposition, apoptosis, and damage in the kidney. Therefore, we propose SIRT1 as a potential target for preventing disease progression in patients with kidney stones.

Functional biochar fabricated from red mud and walnut shell for phosphorus wastewater treatment: Role of minerals.

A novel functional biochar (BC) was prepared from industrial waste red mud (RM) and low-cost walnut shell by one facile-step pyrolysis method to adsorb phosphorus (P) in wastewater. The preparation conditions for RM-BC were optimized using Response Surface Methodology. The adsorption characteristics of P were investigated in batch mode experiments, while a variety of techniques were used to characterize RM-BC composites. The impact of key minerals (hematite, quartz, and calcite) in RM on the P removal efficiency of the RM-BC composite was studied. The results showed that RM-BC composite produced at 320 °C for 58 min, with a 1:1 mass ratio of walnut shell and RM, had a maximum P sorption capacity of 15.48 mg g-1, which was more than double that of the raw BC. The removal of P from water was found to be facilitated significantly by hematite, which forms Fe-O-P bonds, undergoes surface precipitation, and exchanges ligands. This research provides evidence for the effectiveness of RM-BC in treating P in water, laying the foundation for future scaling-up trials.

Hypermethylation suppresses microRNA-219a-2 to activate the ALDH1L2/GSH/PAI-1 pathway for fibronectin degradation in renal fibrosis.

Epigenetic regulations, such as DNA methylation and microRNAs, play an important role in renal fibrosis. Here, we report the regulation of microRNA-219a-2 (mir-219a-2) by DNA methylation in fibrotic kidneys, unveiling the crosstalk between these epigenetic mechanisms. Through genome-wide DNA methylation analysis and pyro-sequencing, we detected the hypermethylation of mir-219a-2 in renal fibrosis induced by unilateral ureter obstruction (UUO) or renal ischemia/reperfusion, which was accompanied by a significant decrease in mir-219a-5p expression. Functionally, overexpression of mir-219a-2 enhanced fibronectin induction during hypoxia or TGF-ß1 treatment of cultured renal cells. In mice, inhibition of mir-219a-5p suppressed fibronectin accumulation in UUO kidneys. ALDH1L2 was identified to be the direct target gene of mir-219a-5p in renal fibrosis. Mir-219a-5p suppressed ALDH1L2 expression in cultured renal cells, while inhibition of mir-219a-5p prevented the decrease of ALDH1L2 in UUO kidneys. Knockdown of ALDH1L2 enhanced PAI-1 induction during TGF-ß1 treatment of renal cells, which was associated with fibronectin expression. In conclusion, the hypermethylation of mir-219a-2 in response to fibrotic stress attenuates mir-219a-5p expression and induces the up-regulation of its target gene ALDH1L2, which may reduce fibronectin deposition by suppressing PAI-1.

p53 deacetylation alleviates calcium oxalate deposition-induced renal fibrosis by inhibiting ferroptosis.

Calcium oxalate (CaOx) stones are among the most common types of kidney stones and are associated with renal tubular damage, interstitial fibrosis, and chronic kidney disease. The mechanism of CaOx crystal-induced renal fibrosis remains unknown. Ferroptosis, a type of regulated cell death, is characterised by iron-dependent lipid peroxidation, and the tumour suppressor p53 is a key regulator of ferroptosis. In the present study, our results demonstrated that ferroptosis was significantly activated in patients with nephrolithiasis and hyperoxaluric mice as well as verified the protective effects of ferroptosis inhibition on CaOx crystal-induced renal fibrosis. Moreover, the single-cell sequencing database, RNA-sequencing, and western blot analysis revealed that the expression of p53 was increased in patients with chronic kidney disease and the oxalate-stimulated human renal tubular epithelial cell line, HK-2. Additionally, the acetylation of p53 was enhanced by oxalate stimulation in HK-2 cells. Mechanistically, we found that the induction of p53 deacetylation, owing to either the SRT1720-induced activation of deacetylase sirtuin 1 or the triple mutation of p53, inhibited ferroptosis and alleviated renal fibrosis caused by CaOx crystals. We conclude that ferroptosis is one of the critical mechanisms contributing to CaOx crystal-induced renal fibrosis, and the pharmacological induction of ferroptosis via sirtuin 1-mediated p53 deacetylation may be a potential target for preventing renal fibrosis in patients with nephrolithiasis.