Synthesis of terpinyl acetate from α-pinene catalyzed by α-hydroxycarboxylic acid-boric acid composite catalyst.

To enhance the yield of the one-step synthesis of terpinyl acetate from α-pinene and acetic acid, this study evaluated α-hydroxycarboxylic acid (HCA)-boric acid composite catalysts based on orthogonal experimental design. The most important factor affecting the terpinyl acetate content in the product was the HCA content. The catalytic performance of the composite catalyst was related to the pKa1 of HCA. The tartaric acid-boric acid composite catalyst showed the highest catalytic activity. The α-pinene conversion reached 91.8%, and the terpinyl acetate selectivity reached 45.6%. When boric acid was replaced with B2O3, the HCA composite catalyst activity was enhanced, which reduced the use of HCA. When the lactic acid and B2O3 content accounted for 10% and 4% of the α-pinene mass content, respectively, the α-pinene conversion reached 93.2%, and the terpinyl acetate selectivity reached up to 47.1%. In addition, the presence of water was unfavorable to HCA-boric acid composite catalyst. However, a water content less than 1% of the α-pinene mass content improved the catalytic activity of HCA-B2O3. When the tartaric acid-B2O3 was used as catalyst, and the water content was 1% of the α-pinene mass content, the α-pinene conversion was 89.6%, and the terpinyl acetate selectivity was 47.5%.

Twenty years of Gendicine® rAd-p53 cancer gene therapy: The first-in-class human cancer gene therapy in the era of personalized oncology.

Genetic mutations in TP53 contribute to human malignancies through various means. To date, there have been a variety of therapeutic strategies targeting p53, including gene therapy to restore normal p53 function, mutant p53 rescue, inhibiting the MDM2-p53 interaction, p53-based vaccines, and a number of other approaches. This review focuses on the functions of TP53 and discusses the aberrant roles of mutant p53 in various types of cancer. Recombinant human p53 adenovirus, trademarked as Gendicine, which is the first anti-tumor gene therapy drug, has made tremendous progress in cancer gene therapy. We herein discuss the biological mechanisms by which Gendicine exerts its effects and describe the clinical responses reported in clinical trials. Notably, the clinical studies suggest that the combination of Gendicine with chemotherapy and/or radiotherapy may produce more pronounced efficacy in slowing tumor growth and progression than gene therapy/chemotherapy alone. Finally, we summarize the methods of administration of recombinant human p53 adenovirus for different cancer types to provide a reference for future clinical trials.

Leveraging a disulfidptosis/ferroptosis-based signature to predict the prognosis of lung adenocarcinoma.

BACKGROUND: Disulfidptosis and Ferroptosis are two novel forms of cell death. Although their mechanisms differ, research has shown that there is a relationship between the two. Investigating the connection between these two forms of cell death can further deepen our understanding of the development and progression of cancer, and provide better prediction models for accurate prognosis. METHODS: In this study, RNA sequencing (RNA-seq) data, clinical data, single nucleotide polymorphism (SNP) data, and single-cell sequencing data were obtained from public databases. We used weighted gene co-expression network analysis (WGCNA) and unsupervised clustering to identify new Disulfidptosis/Ferroptosis-Related Genes (DFRG), and constructed a LASSO COX prognosis model that was externally validated. To further explore this novel signature, pathway and function analysis was performed, and differences in gene mutation frequency between high- and low-risk groups were studied. Importantly, we also conducted research on immune checkpoint, immune cell infiltration levels and immune resistance indicators, in addition to analyzing real clinical immunotherapy data. RESULTS: We have identified four optimal disulfidptosis/ferroptosis-related genes (ODFRGs) that are differentially expressed and associated with the prognosis of Lung Adenocarcinoma (LUAD). These genes include GMPR, MCFD2, MRPL13, and SALL2. Based on these ODFRGs, we constructed a robust prognostic model in this study, and the high-risk group showed significantly lower overall survival (OS) compared to the low-risk group. Furthermore, this model can also predict the immunotherapy outcomes of LUAD patients to some extent.

Efficacy analysis of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy as a first-line Helicobacter pylori eradication regimen - An open-label, randomized trial.

This research aimed to evaluate the eradication efficacy, safety, and gastrointestinal symptom relief rates of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy in primary eradication patients in Yangzhou, China. It also investigated the possible factors influencing the success of different Helicobacter pylori eradication regimens. A single-center, prospective, open-label, randomized controlled study was performed from December 2020 and October 2021, in which 255 patients with H. pylori infection were assigned in a 1:1:1 ratio to the three different groups. Our results showed that high-dose dual therapy (91.0%, 71/78) and resistance gene-based triple therapy (94.9%, 75/79) achieved eradication rates and compliance equivalent to those of empirical bismuth quadruple therapy (85.3%, 64/75) in the per-protocol analysis, while high-dose dual therapy had lower rates of adverse events (11.5%, 9/78, P < 0.05), fewer side effects, and greater safety. Most patients' gastrointestinal discomfort symptoms improved after eradication of H. pylori. Poor compliance (P < 0.05) and antibiotic resistance (P < 0.05) were risk factors for the efficacy of H. pylori eradication. Therefore, the appropriate regimen can be individualized for eradication therapy in clinical practice according to the patient's resistance and tolerance to the drug.

Building Coarse to Fine Convex Hulls with Auxiliary Vertices for Palette-based Image Recoloring.

Constructing a convex hull for the pixel colors of an image by viewing them as 3D points can extract a set of palette colors for the image, then image recoloring can be achieved by modifying the palette colors. For better recoloring effect, the convex hull should contain more pixels (inclusive) and be more compact. Otherwise, reconstruction error would occur or the extracted palette color would be less representative, yielding wrong recoloring results or less effective edit. We observe that convex hulls constructed by prior methods can contain all the image pixels, but are far from compact. Efforts have been made to optimize the vertices of convex hull to increase the compactness but are still not perfect. In this paper, we propose a novel coarse to fine convex hull construction scheme with auxiliary vertices. We start by constructing a coarse convex hull whose vertices are directly image pixels which is thus the most compact but cannot contain all pixels. We then make a remedy by adding auxiliary vertices into the coarse convex hull to obtain a fine convex hull. More auxiliary vertices are added, more image pixels will be contained into the fine convex hull. The auxiliary vertices are image pixels too so that the compactness can still be maintained. During editing, the auxiliary vertices are not allowed to be edited for edit convenience, but deformed as-rigid-as-possible with the adjusting of other vertices. Our convex hull is both inclusive and compact. Extensive experiments validate the effectiveness of the proposed method.

Effect of Boric Acid on the Ionization Equilibrium of α-Hydroxy Carboxylic Acids and the Study of Its Applications.

To investigate the synergistic catalytic effects of boric acid and α-hydroxycarboxylic acids (HCAs), we analyzed and measured the effects of the complexation reactions between boric acid and HCAs on the ionization equilibrium of the HCAs. Eight HCAs, glycolic acid, D-(-)-lactic acid, (R)-(-)-mandelic acid, D-gluconic acid, L-(-)-malic acid, L-(+)-tartaric acid, D-(-)-tartaric acid, and citric acid, were selected to measure the pH changes in aqueous HCA solutions after adding boric acid. The results showed that the pH values of the aqueous HCA solutions gradually decreased with an increase in the boric acid molar ratio, and the acidity coefficients when boric acid formed double-ligand complexes with HCAs were smaller than those of the single-ligand complexes. The more hydroxyl groups the HCA contained, the more types of complexes could be formed, and the greater the rate of change in the pH. The total rates of change in the pH of the HCA solutions were in the following order: citric acid > L-(-)-tartaric acid = D-(-)-tartaric acid > D-gluconic acid > (R)-(-)-mandelic acid > L-(-)-malic acid > D-(-)-lactic acid > glycolic acid. The composite catalyst of boric acid and tartaric acid had a high catalytic activity-the yield of methyl palmitate was 98%. After the reaction, the catalyst and methanol could be separated by standing stratification.

Image acquisition as novel colonoscopic quality indicator: a single-center retrospective study.

Purpose: In order to reduce the incidence and mortality of colorectal cancer, improving the quality of colonoscopy is the top priority. At present, the adenoma detection rate is the most used index to evaluate the quality of colonoscopy. So, we further verified the relevant factors influencing the quality of colonoscopy and found out the novel quality indicators by studying the relationship between the influencing factors and the adenoma detection rate. Materials/methods: The study included 3824 cases of colonoscopy from January to December 2020. We retrospectively recorded the age and sex of the subjects; the number, size, and histological features of lesions; withdrawal time and the number of images acquired during colonoscopy. We analyzed the associated factors affecting adenoma and polyp detection, and verified their effectiveness with both univariate and multivariate logistic regression analyses. Results: Logistic regression analyses showed that gender, age, withdrawal time and the number of images acquired during colonoscopy could serve as independent predictors of adenoma/polyp detection rate. In addition, adenoma detection rate (25.36% vs. 14.29%) and polyp detection rate (53.99% vs. 34.42%) showed a marked increase when the number of images taken during colonoscopy was ≥29 (P<0.001). Conclusions: Gender, age, withdrawal time and the number of images acquired during colonoscopy are influencing factors for the detection of colorectal adenomas and polyps. And we can gain higher adenoma/polyp detection rate when endoscopists capture more colonoscopic images.

Pan-cancer analysis of super enhancer-induced PRR7-AS1 as a potential prognostic and immunological biomarker.

Introduction: Systematic pan-cancer analysis of the roles and regulatory mechanisms for PRR7-AS1 is currently not available. Methods: In the present study, a comprehensive bioinformatic approach was used to mine the underlying oncogenic effects of PRR7-AS1, including expression status, prognostic value and immune characteristics. Results: We discovered that PRR7-AS1 expression was remarkably upregulated in most cancer types and exhibited a negative correlation with the prognosis. Furthermore, PRR7-AS1 expression was inversely connected with the majority of tumor-infiltrating immune cells, immune scores and immune checkpoint gene expression in pancancer. There was also a significant correlation between PRR7-AS1 expression status and tumor mutational burden, microsatellite instability, and neoantigens in certain tumors. PRR7-AS1 had the best predictive power for immune checkpoint blockade efficacy compared to other well-recognized biomarkers. PRR7-AS1 overexpression could affect cytotoxic T cells-mediated antitumor responses. Functional enrichment analysis revealed that PRR7-AS1 might be involved in the metabolic pathways. Super enhancer activity might have participated in the regulation of PRR7-AS1 expression. And we constructed the competitive endogenous RNA networks for PRR7-AS1. Discussion: In general, PRR7-AS1 had the potential to be a diagnostic, prognostic and immune biomarker for pan cancer. PRR7-AS1 was correlated with an immunosuppressive microenvironment and was a new potential target for immunotherapy. Epigenetic factors were the driving forces for PRR7-AS1 overexpression in tumors.

Study on the Hydration of α-Pinene Catalyzed by α-Hydroxycarboxylic Acid-Boric Acid Composite Catalysts.

In this study, seven types of α-hydroxycarboxylic acids were selected to form composite catalysts with boric acid, and their catalytic properties were studied using the catalytic hydration of α-pinene. The results showed that the composite catalyst of boric acid and tartaric acid had the highest catalytic activity. With an α-pinene, water, acetic acid, tartaric acid, and boric acid mass ratio of 10:10:25:0.5:0.4, the reaction temperature was 60 °C, the reaction time was 24 h, the conversion of α-pinene was 96.1%, and the selectivity of terpineol was 58.7%. The composite catalyst composed of boric acid and mandelic acid directly catalyzed the hydration of α-pinene in the absence of a solvent. Under the optimal conditions, the conversion of α-pinene reached 96.1%, and the selectivity of terpineol was 55.5%. When the composite catalyst catalyzed α-pinene to synthesize terpineol in one step, the terpineol was optically active, and terpineol synthesized using the two-step method with the dehydration of p-menthane-1,8-diol monohydrate was racemic. These composite catalysts may offer good application prospects in the synthesis of terpineol.

Study on Synthesizing Isobornyl Acetate/Isoborneol from Camphene Using α-Hydroxyl Carboxylic Acid Composite Catalyst.

This study examined the preparation of isobornyl acetate/isoborneol from camphene using an α-hydroxyl carboxylic acid (HCA) composite catalyst. Through the study of the influencing factors, it was found that HCA and boric acid exhibited significant synergistic catalysis. Under optimal conditions, when tartaric acid-boric acid was used as the catalyst, the conversion of camphene and the gas chromatography (GC) content and selectivity of isobornyl acetate were 92.9%, 88.5%, and 95.3%, respectively. With the increase in the ratio of water to acetic acid, the GC content and selectivity of isobornol in the product increased, but the conversion of camphene decreased. The yield of isobornol was increased by adding ethyl acetate or titanium sulfate/zirconium sulfate to form a ternary composite catalyst. When a ternary complex of titanium sulfate, tartaric acid, and boric acid was used as the catalyst, the GC content of isobornol in the product reached 55.6%. Under solvent-free conditions, mandelic acid-boric acid could catalyze the hydration reaction of camphene, the GC content of isoborneol in the product reached 26.1%, and the selectivity of isoborneol was 55.9%. The HCA-boric acid composite catalyst can use aqueous acetic acid as a raw material, which is also beneficial for the reuse of the catalyst.

Yarn-Level Simulation of Hygroscopicity of Woven Textiles.

Simulating liquid-textile interaction has received great attention in computer graphics recently. Most existing methods take textiles as particles or parameterized meshes. Although these methods can generate visually pleasing results, they cannot simulate water content at a microscopic level due to the lack of geometrically modeling of textile's anisotropic structure. In this paper, we develop a method for yarn-level simulation of hygroscopicity of textiles and evaluate it using various quantitative metrics. We model textiles in a fiber-yarn-fabric multi-scale manner and consider the dynamic coupled physical mechanisms of liquid spreading, including wetting, wicking, moisture sorption/desorption, and transient moisture-heat transfer in textiles. Our method can accurately simulate liquid spreading on textiles with different fiber materials and geometrical structures with consideration of air temperatures and humidity conditions. It visualizes the hygroscopicity of textiles to demonstrate their moisture management ability. We conduct qualitative and quantitative experiments to validate our method and explore various factors to analyze their influence on liquid spreading and hygroscopicity of textiles.

Complexation of Boronic Acid with Chiral α-Hydroxycarboxylic Acids and the Ability of the Complexes to Catalyze α-Hydroxycarboxylic Acid Esterification.

The complexation of boric acid (BA) with various α-hydroxycarboxylic acids (HCAs) was examined by analyzing the change in the optical rotation after the addition of BA to aqueous HCA solutions, and the catalytic properties of the complexes were examined by catalyzing the esterification of the HCAs. The absolute values of the optical rotation of the HCAs increased with increasing BA-to-HCA molar ratio, and the rate of change of the optical rotation gradually decreased as the BA-to-HCA molar ratio increased, reaching a minimum value at a molar ratio of approximately three. As a catalyst, BA could catalyze the acetylation of hydroxyl groups in addition to the esterification of HCAs. Compared to the conventional synthesis routes of ATBC and ATOC, a synthesis route with BA as the catalyst allowed for a lower frequency of catalyst separation and replacement while providing light-colored products. BA could catalyze the formation of triethyl citrate, and the yield of triethyl citrate reached 93.8%. BA could also catalyze the reaction between malic acid and pinene to produce borneol malate. After saponification of borneol malate, borneol was obtained with a yield of 39%.

LIGHT deficiency attenuates acute kidney disease development in an in vivo experimental renal ischemia and reperfusion injury model.

Ischemia-reperfusion (I/R), a leading risk factor of acute kidney injury (AKI), is associated with high mortality and risk of progression to chronic kidney disease. However, the molecular mechanism of I/R-AKI remains not fully understood, which hinders its efficient clinical treatment. In this study, we observed that LIGHT deficiency remarkably attenuated I/R-AKI, as evidenced by rescued renal function, ameliorated tubular cell apoptosis, and alleviated inflammatory responses. Consistently, blocking LIGHT signaling with its soluble receptor fusion proteins (HVEM-IgG-Fc or LTßR-IgG-Fc) improved I/R renal dysfunction. RNA-sequencing and corresponding results indicated that LIGHT promoted oxidative stress and inflammation triggered by ischemic injury. Moreover, LIGHT signaling augmented ischemic stress-induced mitochondrial dysfunction characterized by an imbalance in mitochondrial fission and fusion, decreased mtDNA copies, impaired mitophagy, and increased mitochondrial membrane potential (ΔΨm). Mechanistically, LIGHT promoted mitochondrial fission by enhancing Drp1 phosphorylation (Ser616) and its translocation to the mitochondria. In conclusion, these results suggest that LIGHT-HVEM/LTßR signaling is critical for the I/R-AKI pathogenesis and it is further confirmed to be related to the increase in I/R-induced oxidative stress and mitochondria dysfunction, which may be the underlying mechanism of LIGHT signaling-mediated I/R-AKI.

The predictive value of routine laboratory tests for colorectal polyps: a retrospective study.

Background: Colorectal cancer (CRC) has become the malignant tumor of the digestive tract with the highest incidence in our country, posing a serious threat to the health of our people. Early colon cancer is mostly due to the malignant transformation of colon polyps, so that early detection and resection have been shown to be effective in reducing the incidence and mortality of CRC. This study tried to investigate the related risk factors of and construct a predictive nomogram for colorectal polyps, providing meaningful guidance basis for risk stratification and screening. Methods: A total of 1,799 patients who underwent colonoscopies in the Health Management Centre of the Affiliated Hospital of Yangzhou University were recruited to this study. Univariate and multivariate logistic analyses were performed to determine the risk factors for colorectal polyps, and a predictive nomogram was constructed based on the multivariable model. We determined the predictive value of the nomogram by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analyses (DCAs). Results: The logistic regression analysis showed that age (P<0.001), gender (P<0.001), eosinophil count (P=0.005), hemoglobin level (P=0.039), and LDL-C/HDL-C ratio (LHR; P<0.001) were independent predictors of the development of colorectal polyps. The above independent risk factors were incorporated, and an individualized nomogram model was successfully established. The C-index of the nomogram was 0.679 in our model, and with the bootstrap method, the prediction curve fit well with the ideal curve, suggesting that the prediction curve constructed in this study has good predictive ability. Conclusions: Age, gender, eosinophil count, hemoglobin level, and LHR are risk factors for the development of colorectal polyps. Establishing a nomogram prediction model for colorectal polyps is helpful for the early clinical screening of high-risk patients with colorectal polyps, improving the detection rate of polyps and reducing the incidence of colorectal cancer (CRC).

Relationship between fatty pancreas and hypertriglyceridemic waist phenotype: a cross-sectional study.

Hypertriglyceridemic waist phenotype (HTWP) and its quantitative indicator, waist circumference-triglyceride index (WTI), are common quantitative indices of visceral obesity and are closely related to metabolic diseases. The purpose of this study was to investigate the relationship between fatty pancreas (FP) and HTWP in China. FP was diagnosed using trans-abdominal ultrasonography in all participants. According to the waist circumference and serum triglyceride levels, the participants were divided into four phenotype groups: normal waist circumference-normal triglyceride, normal waist circumference-elevated triglyceride, elevated waist circumference-normal triglyceride, and elevated waist circumference-elevated triglyceride (indicating HTWP). Clinical characteristics and biochemical indices were compared among the groups. Receiver operating characteristic (ROC) curves were used to evaluate the utility of WTI as a reference factor for FP screening. The HTWP group had a higher prevalence of metabolic syndrome (84.2%), FP (10.4%), fatty liver (64.5%), and hypertension (15.8%) than the other three phenotype groups. The occurrence rate of HTWP and the median WTI were significantly higher in participants with FP than in those without FP (54.7% vs 21.0%, 222 ± 135 vs 142 ± 141, p < 0.001). In the ROC curve analysis, when the maximum area under the curve was 0.746, the WTI was 107.09 and the corresponding sensitivity and specificity were 90.6% and 51.9%, respectively. HTWP is closely associated with FP and can be used as a reference factor for FP screening.

Tumor necrosis factor superfamily 14 is critical for the development of renal fibrosis.

OBJECTIVE: Tumor necrosis factor superfamily protein 14 (TNFSF14) was recently identified as a risk factor in some fibrosis diseases. However, the role of TNFSF14 in renal fibrosis pathogenesis remains unknown. RESULTS: It was found that TNFSF14 levels were significantly increased both in UUO-induced renal fibrotic mice and in patients with fibrotic nephropathy, compared with those in controls. Accordingly, Tnfsf14 deficiency led to a marked reduction in renal fibrosis lesions and inflammatory cytokines expression in the UUO mice. Furthermore, the levels of Sphk1, a critical molecule that causes fibrotic nephropathy, were remarkably reduced in Tnfsf14 KO mice with UUO surgery. In vitro recombinant TNFSF14 administration markedly up-regulated the expression of Sphk1 of primary mouse renal tubular epithelial cells (mTECs). CONCLUSION: TNFSF14 is a novel pro-fibrotic factor of renal fibrosis, for which TNFSF14 up-regulates Sphk1 expression, which may be the underlying mechanism of TNFSF14-mediated renal fibrosis. METHODS: We investigated the effect of TNFSF14 on renal fibrosis and the relationship between TNFSF14 and pro-fibrotic factor sphingosine kinase 1 (Sphk1) by using the unilateral urethral obstruction (UUO)-induced mice renal fibrosis as a model and the specimen of patients with fibrosis nephropathy, by Masson trichrome staining, immunohistochemistry, qRT-PCR, and western blot analysis.

LIGHT deficiency aggravates cisplatin-induced acute kidney injury by upregulating mitochondrial apoptosis.

Cisplatin is widely used as a chemotherapeutic agent for treating patients with solid tumors. The most common side effect of cisplatin treatment is nephrotoxicity. Recent studies have shown that mitochondrial apoptotic pathways are involved in cisplatin-induced acute kidney injury (Cis-AKI). LIGHT, the 14th member of the tumor necrosis factor superfamily (TNFSF14), was found to induce apoptosis of certain types of tumor cells. So far, a link between LIGHT and Cis-AKI has not been reported. In this study, we observed that expression of LIGHT and its receptors HVEM and LTßR was increased in kidney tissues of mice after cisplatin treatment. LIGHT deficiency aggravated kidney injury, as evidenced by more severe tubular injury; remarkably increased levels of serum creatinine (Scr), blood urea nitrogen (BUN), and both kidney injury molecule-1 (KIM-1) and inflammatory cytokine mRNAs in renal tissues. Moreover, in the renal tissues of LIGHT KO mice, cisplatin-induced mitochondrion injury and the levels of the pro-apoptotic molecules Bax, Cytochrome C (Cyt C), cleaved caspase-3, and cleaved caspase-9 were dramatically increased; in contrast, the expression of anti-apoptotic molecule Bcl-2 was markedly reduced, compared to those in WT mice, suggesting that LIGHT deficiency accelerated cisplatin-induced mitochondrial apoptosis of renal tubular cells in these mice. Accordingly, treatment with recombinant human LIGHT (rLIGHT) was shown to alleviate cisplatin-induced kidney injury in vivo. Similar results were observed after the human renal tubular epithelial cell line HK-2 cells exposure to rLIGHT stimulation, evidenced by the reduction in the mitochondrion dysfunction (as confirmed by the significant reduced oxidative stress and membrane potential changes) and in the percentage of cells apoptosis. While blocking LIGHT with the soluble fusion protein LTßR-Ig or HVEM-Ig accelerated the HK-2 cells apoptosis. In conclusion, LIGHT deficiency aggravates Cis-AKI by promoting mitochondrial apoptosis pathways.

LIGHT aggravates sepsis-associated acute kidney injury via TLR4-MyD88-NF-κB pathway.

Sepsis-associated acute kidney injury (SA-AKI) is a common clinical critical care syndrome. It has received increasing attention due to its high morbidity and mortality; however, its pathophysiological mechanisms remain elusive. LIGHT, the 14th member of the tumour necrosis factor (TNF) superfamily and a bidirectional immunoregulatory molecule that regulates inflammation, plays a pivotal role in disease pathogenesis. In this study, mice with an intraperitoneal injection of LPS and HK-2 cells challenged with LPS were employed as a model of SA-AKI in vivo and in vitro, respectively. LIGHT deficiency notably attenuated kidney injury in pathological damage and renal function and markedly mitigated the inflammatory reaction by decreasing inflammatory mediator production and inflammatory cell infiltration in vivo. The TLR4-Myd88-NF-κB signalling pathway in the kidney of LIGHT knockout mice was dramatically down-regulated compared to the controls. Recombinant human LIGHT aggravated LPS-treated HK-2 cell injury by up-regulating the expression of the TLR4-Myd88-NF-κB signalling pathway and inflammation levels. TAK 242 (a selective TLR4 inhibitor) reduced this trend to some extent. In addition, blocking LIGHT with soluble receptor fusion proteins HVEM-Fc or LTßR-Fc in mice attenuated renal dysfunction and pathological damage in SA-AKI. Our findings indicate that LIGHT aggravates inflammation and promotes kidney damage in LPS-induced SA-AKI via the TLR4-Myd88-NF-κB signalling pathway, which provide potential strategies for the treatment of SA-AKI.

Fibrinogen-like protein 2 deficiency aggravates renal fibrosis by facilitating macrophage polarization.

Renal fibrosis has no effective target for its prevention or reversal. Fibinogen-like protein 2 (Fgl2) is a novel prothrombinase exhibiting coagulation activity and immunomodulatory effects. Although Fgl2 is known to play a vital role in the development of liver and interstitial fibrosis, its function in renal fibrosis remains unclear. In this study, Fgl2 expression was found to be markedly increased in kidney tissues from mice with unilateral ureteral obstruction (UUO)-induced renal fibrosis and patients with chronic kidney disease. However, Fgl2 deficiency aggravated UUO-induced renal fibrosis, as evidenced by the significantly increasing collagen I, fibronectin, and α-SMA expression, extracellular matrix deposition, and profibrotic factor (TGF-ß1) secretion. Administration of rmFgl2 (recombinant mouse Fgl2) significantly alleviated UUO-induced renal fibrosis in mice, suggesting that the increased fibrosis can be reversed by supplementing rmFgl2. Although there was no difference in the percentages of total macrophages between Fgl2+/+ and Fgl2-/- mice, Fgl2 deficiency remarkably facilitated M2 macrophage polarization and accelerated M1 macrophage polarization to a low degree, during UUO-induced renal fibrosis development in mice. Similar results were observed when Fgl2+/+ and Fgl2-/- mice bone marrow-derived macrophages were treated for M1 or M2 polarization. Moreover, Fgl2 deficiency significantly increased the phosphorylation of STAT6, a critical mediator of M2 polarization, in both UUO-induced fibrotic kidney tissues and bone marrow-derived M2 macrophages. In conclusion, the aggravation of renal fibrosis by Fgl2 deficiency is facilitated by the p-STAT6-dependent upregulation of macrophage polarization, especially of M2.