The TRIM28/miR133a/CD47 axis acts as a potential therapeutic target in pancreatic necrosis by impairing efferocytosis.

Efferocytosis, the clearance of apoptotic cells by macrophages, plays a crucial role in inflammatory responses and effectively prevents secondary necrosis. However, the mechanisms underlying efferocytosis in acute pancreatitis (AP) remain unclear. In this study, we demonstrated the presence of efferocytosis in injured human and mouse pancreatic tissues. We also observed significant upregulation of CD47, an efferocytosis-related the "do not eat me" molecule in injured acinar cells. Subsequently, we used CRISPR-Cas9 gene editing, anti-adeno-associated virus (AAV) gene modification, and anti-CD47 antibody to investigate the potential therapeutic role of AP. CD47 expression was negatively regulated by upstream miR133a, which is controlled by the transcription factor TRIM28. To further investigate the regulation of efferocytosis and reduction of pancreatic necrosis in AP, we used miR-133a-agomir and pancreas-specific AAV-shTRIM28 to modulate CD47 expression. Our findings confirmed that CD47-mediated efferocytosis is critical for preventing pancreatic necrosis and suggest that targeting the TRIM28-miR133a-CD47 axis is clinically relevant for the treatment of AP.

Associations of Intrapancreatic Fat Deposition With Incident Diseases of the Exocrine and Endocrine Pancreas: A UK Biobank Prospective Cohort Study.

INTRODUCTION: To investigate whether increased intrapancreatic fat deposition (IPFD) heightens the risk of diseases of the exocrine and endocrine pancreas. METHODS: A prospective cohort study was conducted using data from the UK Biobank. IPFD was quantified using MRI and a deep learning-based framework called nnUNet. The prevalence of fatty change of the pancreas (FP) was determined using sex- and age-specific thresholds. Associations between IPFD and pancreatic diseases were assessed with multivariate Cox-proportional hazard model adjusted for age, sex, ethnicity, body mass index, smoking and drinking status, central obesity, hypertension, dyslipidemia, liver fat content, and spleen fat content. RESULTS: Of the 42,599 participants included in the analysis, the prevalence of FP was 17.86%. Elevated IPFD levels were associated with an increased risk of acute pancreatitis (hazard ratio [HR] per 1 quintile change 1.513, 95% confidence interval [CI] 1.179-1.941), pancreatic cancer (HR per 1 quintile change 1.365, 95% CI 1.058-1.762) and diabetes mellitus (HR per 1 quintile change 1.221, 95% CI 1.132-1.318). FP was also associated with a higher risk of acute pancreatitis (HR 3.982, 95% CI 2.192-7.234), pancreatic cancer (HR 1.976, 95% CI 1.054-3.704), and diabetes mellitus (HR 1.337, 95% CI 1.122-1.593, P = 0.001). DISCUSSION: FP is a common pancreatic disorder. Fat in the pancreas is an independent risk factor for diseases of both the exocrine pancreas and endocrine pancreas.

Paeonol protects against acute pancreatitis by inhibiting M1 macrophage polarization via the NLRP3 inflammasomes pathway.

The excessive inflammatory response mediated by macrophage is one of the key factors for the progress of acute pancreatitis (AP). Paeonol (Pae) was demonstrated to exert multiple anti-inflammatory effects. However, the role of Pae on AP is not clear. In the present study, we aimed to investigate the protective effect and mechanism of Pae on AP in vivo and vitro. In the caerulein-induced mild acute pancreatitis (MAP) model, we found that Pae administration reduced serum levels of amylase, lipase, IL-1ß and IL-6 and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. And Pae decrease the ROS generated, restore mitochondrial membrane potential (ΔΨm), inhibit M1 macrophage polarization and NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs) in vitro. In addition, specific NLRP3 inhibitor MCC950 eliminated the protective effect of Pae on AP induced by caerulein in mice. Correspondingly, the inhibitory effect of Pae on ROS generated and M1 polarization was not observed in BMDMs with MCC950 in vitro. Taken together, our datas for the first time confirmed the protective effects of Pae on AP via the NLRP3 inflammasomes Pathway.

Elevated serum ferritin levels are associated with severity and prognosis of severe acute pancreatitis: a preliminary cohort study.

BACKGROUND: Serum ferritin (SF), as an acute-phase response protein, is used to reflect the degree of oxidative stress and systemic inflammatory responses. This study was designed to assess the effect of elevated SF levels on the severity of acute pancreatitis (AP). METHODS: From January 2013 to December 2020, 200 consecutive patients with AP were retrospectively reviewed to analyze the relationships among the etiologies of pancreatitis, the severity of the disease and SF levels. The receiver operating characteristic (ROC) curve and logistic regression analysis were used to assess whether elevated SF levels could predict the onset of organ failure in AP. RESULTS: 92 (46%) had high SF levels (> 275 ng/ml). SF levels were not associated with the etiology of AP disease. Among patients with high SF levels, there was a significant increase in the proportion of patients with severe AP (23.1% vs. 76.9%) and a higher proportion of systemic inflammatory response scores (25.9% vs. 44.6%) in comparison to patients with normal SF levels. The area under the ROC curve for SF in predicting persistent organ failure was 0.812 [95% confidence interval 0.721-0.904]. CONCLUSIONS: F concentrations were positively correlated with the severity of AP, and quantitative assessment of SF can predict disease severity and organ failure in patients with AP.

Inhibition of hypoxia-inducible factor-1α alleviates acinar cell necrosis in a mouse model of acute pancreatitis.

Hypoxia-inducible factor-1α (Hif1α) is activated in hypoxia and is closely related to oxidative stress, immunity and cell metabolism. Recently, it is reported that Hif1α is involved in atherosclerosis, ischemia-reperfusion (I/R) injury, alcoholic liver disease and pancreatic tumors. In this study, we found that Hif1 signal pathway is significantly changed in pancreas of acute pancreatitis (AP) mice. Meanwhile, we verified that the high expression of Hif1α injured pancreatic tissues of cerulean-induced AP mice, which prompting that Hif1α participated in the progress of histopathology on AP. We applied a Hif1α inhibitor PX478 and observed that it could alleviate histological injury of pancreas as well as the levels of serum amylase, lipase and proinflammatory cytokine in the murine model of AP induced by caerulein. In addition, PX478 could reduce the formation of necrosome (RIP3 and p-MLKL) and the generation of reactive oxygen species (ROS) in AP mice. Correspondingly, we further confirmed the effectiveness of PX478 in vitro and found that inhibiting Hif1α could mitigated the necrosis of pancreatic acinar cells via reducing the RIP3 and p-MLKL expression and the ROS production. In conclusion, inhibiting Hif1α could protect against acinar cells necrosis in AP, which may provide a new target for the prevention and treatment of AP clinically.

The Proresolving Lipid Mediator Maresin1 Alleviates Experimental Pancreatitis via Switching Macrophage Polarization.

METHOD: Repeated caerulein injection was used to induce AP and chronic pancreatitis (CP) models in mice. The histopathological and serological changes were examined for evaluating the severity of the AP model, and flow cytometry was used for detecting macrophage phagocytosis and phenotype. Meanwhile, clodronate liposomes were used for macrophage depletion in mice. Finally, the CP model was adopted to further observe the protective effect of MaR1. RESULT: MaR1 administration manifested the improved histopathological changes and the lower serum levels of amylase and lipase. However, MaR1 played no protective role in the pancreatic acinar cell line in vitro. It obviously reduced the macrophage infiltration in the injured pancreas, especially M1-type macrophages. After macrophage clearance, MaR1 showed no further protection in vivo. This study also demonstrated that MaR1 could alleviate fibrosis to limit AP progression in the CP model. CONCLUSION: Our data suggests that MaR1 was a therapeutic and preventive target for AP in mice, likely operating through its effects on decreased macrophage infiltration and phenotype switch.

NQDI-1 protects against acinar cell necrosis in three experimental mouse models of acute pancreatitis.

NQDI-1, an inhibitor of ASK1, has been reported to have protective effects in several experimental human disease models. However, the role of NQDI-1 in acute pancreatitis (AP) has not been reported. In this study, we found that NQDI-1 could attenuate histological damage of pancreatic tissue as well as the levels of serum amylase and lipase in a mouse model of AP induced by caerulein. Moreover, the production of reactive oxygen species (ROS) and the expression of necrosis-related proteins (RIP3 and p-MLKL) were also reduced after NQDI-1 administration. Correspondingly, we elucidated the effect of NQDI-1 in vitro and found that NQDI-1 protected against pancreatic acinar cells necrosis via decreasing the ROS production and RIP3 and p-MLKL expression. In addition, we identified the protective effect of NQDI-1 on AP through two other mouse models induced by l-arginine and pancreatic duct ligation. Taken together, these findings showed that NQDI-1 could reduce the acinar cells necrosis and alleviate the severity of AP, which may afford a new therapeutic target on pancreatic necrosis in AP clinically.

Dynamic changes of proteasome and protective effect of bortezomib, a proteasome inhibitor, in mice with acute pancreatitis.

The proteasome is involved in the activation of NF-κB and can regulate the progression of inflammatory diseases. However, the role of proteasome in acute pancreatitis (AP) has not been demonstrated. In this study, we first observed that the protein level and activity of proteasome 20S were increased significantly in pancreatic injury tissues after caerulein-induced mild acute pancreatitis (MAP) induction, which was in consistent with the expression of the NF-κB nucleoprotein and positively correlated with the severity of AP. Then, bortezomib, a classical proteasome inhibitor, was used to intervene the progression of MAP in mice. The results showed that bortezomib administration reduced the serum amylase and lipase levels and mitigated histopathological manifestation of pancreatic injury in mice. Meanwhile, bortezomib decreased the expression of NF-κB p65 nucleoprotein as well as total proteasome 20S protein, and inhibited the activity of 20S in pancreatic tissues. In addition, we found that bortezomib could protect pancreatic acinar cell against necrosis and mitigate the severity of AP in a severe acute pancreatitis model induced by sodium taurocholate hydrate. Taken together, our study for the first time confirmed that the proteasome participated in the pathogenesis of AP and its inhibitor bortezomib could protect against AP in mice.

Prevalence and clinical characteristics of fatty pancreas in Yangzhou, China: A cross-sectional study.

OBJECTIVE: The aim of this study was to investigate the prevalence and risk factors of fatty pancreas in Yangzhou, China. METHODS: This was a cross-sectional study. Initially, 2093 subjects were included in the study. After the exclusion of 865 subjects based on incomplete information, a total of 1228 subjects were selected for further analysis. The subjects were stratified into two groups (the fatty pancreas group and the non-fatty pancreas group) based on the results. Anthropometric and biochemical findings were compared between the groups. RESULTS: Among the 2093 study subjects, 56 (2.7%) had fatty pancreas. Overall, 53 out of 1228 subjects were diagnosed with fatty pancreas and included into the fatty pancreas group. Univariate analysis showed significant differences in age and the prevalence of general obesity, central obesity, alcohol consumption, metabolic syndrome and fatty liver between the two groups (all p < 0.01). The fatty pancreas group had higher levels of aspartate aminotransferase, alanine aminotransferase, serum uric acid, fasting blood glucose, total cholesterol, triglycerides and low-density lipoprotein, and lower levels of high-density lipoprotein than did the non-fatty pancreas group (all p < 0.05). Multivariate logistic regression analysis showed that age (p = 0.007), central obesity (p = 0.002) and fatty liver (p = 0.006) were independent risk factors for fatty pancreas, with odds ratios (ORs) of 1.034 (95% confidence interval (CI): 1.009-1.059), 5.364 (95% CI: 1.890-15.227), and 2.666 (95% CI: 1.332-5.338), respectively. CONCLUSION: The prevalence of fatty pancreas in the examined population is approximately 2.7%. Increased age, central obesity and fatty liver disease are independent risk factors for fatty pancreas.

Corrigendum to "Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway".

[This corrects the article DOI: 10.1155/2018/3048532.].

Formononetin Administration Ameliorates Dextran Sulfate Sodium-Induced Acute Colitis by Inhibiting NLRP3 Inflammasome Signaling Pathway.

Formononetin is a kind of isoflavone compound and has been reported to possess anti-inflammatory properties. In this present study, we aimed to explore the protective effects of formononetin on dextran sulfate sodium- (DSS-) induced acute colitis. By intraperitoneal injection of formononetin in mice, the disease severity of colitis was attenuated in a dose-dependent manner, mainly manifesting as relieved clinical symptoms of colitis, mitigated colonic epithelial cell injury, and upregulations of colonic tight junction proteins levels (ZO-1, claudin-1, and occludin). Meanwhile, our study found that formononetin significantly prevented acute injury of colonic cells induced by TNF-α in vitro, specifically manifesting as the increased expressions of colonic tight junction proteins (ZO-1, claudin-1, and occludin). In addition, the result showed that formononetin could reduce the NLRP3 pathway protein levels (NLRP3, ASC, IL-1ß) in vivo and vitro, and MCC950, the NLRP3 specific inhibitor, could alleviate the DSS-induced mice acute colitis. Furthermore, in the foundation of administrating MCC950 to inhibit activation of NLRP3 inflammasome, we failed to observe the protective effects of formononetin on acute colitis in mice. Collectively, our study for the first time confirmed the protective effects of formononetin on DSS-induced acute colitis via inhibiting the NLRP3 inflammasome pathway activation.

Naringenin Alleviates Radiation-Induced Intestinal Injury by Inhibiting TRPV6 in Mice.

SCOPE: Naringenin (NAR) possesses unique anti-inflammatory, antiapoptosis effects and various bioactivities; however, its role against radiation-induced intestinal injury (RIII) remains unclear. This study aims to investigate whether NAR has protective effects against radiation-induced intestinal injury and the underlying mechanisms. METHODS AND RESULTS: C57BL/6J mice are exposed to a single dose of 13 Gy X-ray total abdominal irradiation (TAI), then gavaged with NAR for 7 days. NAR treatment prolongs the survival rate, protects crypts and villi from damage, alleviates the level of radiation-induced inflammation, and mitigates intestinal barrier damage in the irradiated mice. Additionally, NAR reduces immune cell infiltration and intestinal epithelial cell apoptosis. NAR also shows radioprotective effects in human colon cancer cells (HCT116) and human intestinal epithelial cells (NCM460). It reduces cell damage by reducing intracellular calcium ion levels and reactive oxygen species (ROS) levels. NAR-mediated radioprotection is associated with the downregulation of transient receptor potential vanilloid 6 (TRPV6), and inhibition of apoptosis pathway. Notably, treatment with NAR fails to further increase the protective effects of the TRPV6 inhibitor 2-APB, indicating that TRPV6 inhibition is essential for NAR activity. CONCLUSION: NAR inhibits the apoptosis pathway by downregulating TRPV6 and reducing calcium ion level, thereby alleviating RIII. Therefore, NAR is a promising therapeutic drug for RIII.

CD177 Inhibits Neutrophil Extracellular Trap Formation and Protects against Acute Pancreatitis in Mice.

The inflammatory immune response mediated by neutrophils is closely related to the progression of acute pancreatitis. Previous studies confirmed that CD177 is a neutrophil-specific marker involved in the pathogenesis of conditions such as systemic vasculitis, asthma, and polycythemia vera. Neutrophil extracellular trap (NET) formation is a specific death program by which neutrophils release nuclear DNA covered with histones, granule proteins, etc. It also plays an important role in host defense and various pathological reactions. However, the function of CD177 in regulating the generation of NETs and the development of acute pancreatitis (AP) is unclear. In our manuscript, CD177 was significantly elevated in blood neutrophils in patients and positively correlated with the AP disease severity. Then, recombinant human CD177 protein (rhCD177) could significantly improve pancreatic injury and the inflammatory response in AP mice, and reduce AP-related lung injury. Mechanistically, we found that rhCD177 could inhibit the formation of NETs by reducing reactive oxygen species (ROS) and myeloperoxidase (MPO)/citrullinated histone H3 (CitH3) release. For the first time, we discovered the potential of rhCD177 to protect AP in mice and inhibit the NET formation of AP. CD177 may be a potential treatment strategy for preventing or inhibiting the aggravation of AP.

HDL inhibits pancreatic acinar cell NLRP3 inflammasome activation and protect against acinar cell pyroptosis in acute pancreatitis.

BACKGROUND AND PURPOSE: Recent clinical studies have shown that serum high-density lipoprotein (HDL) levels are correlated with acute pancreatitis (AP) severity. We aimed to investigate the role of HDL in pancreatic necrosis in AP. EXPERIMENTAL APPROACH: ApoA-I is the main constitution and function component of HDL. The roles of healthy human-derived HDL and apoA-I mimic peptide D4F were demonstrated in AP models in vivo and in vitro. Constitutive Apoa1 genetic inhibition on AP severity, especially pancreatic necrosis was assessed in both caerulein and sodium taurocholate induced mouse AP models. In addition, constitutive (Casp1-/-) and acinar cell conditional (Pdx1CreNlrp3Δ/Δ and Pdx1CreGsdmdΔ/Δ) mice were used to explore the effects of HDL on acinar cell pyroptosis in AP. KEY RESULTS: Apoa1 knockout dramatically aggravated pancreatic necrosis. Human-derived HDL protected against acinar cell death in vivo and in vitro. We found that mimic peptide D4F also protected against AP very well. Constitutive Casp1 or acinar cell-conditional Nlrp3 and Gsdmd genetic inhibition could counteract the protective effects of HDL, implying HDL may exert beneficial effects on AP through inhibiting acinar cell pyroptosis. CONCLUSION AND IMPLICATIONS: This work demonstrates the protective role of HDL and apoA-I in AP pathology, potentially driven by the inhibition of NLRP3 inflammasome signaling and acinar cell pyroptosis. Mimic peptides have promise as specific therapies for AP.

Irisin inhibits neutrophil extracellular traps formation and protects against acute pancreatitis in mice.

INTRODUCTION: Irisin is a newly discovered myokine which links exercise to inflammation and inflammation-related diseases through macrophage regulation. However, the effect of irisin on the activity of inflammation related immune cells (such as neutrophils) has not been clearly described. OBJECTIVES: The objective of our study was to explore the effect of irisin on the neutrophil extracellular traps (NETs) formation. METHODS: Phorbol-12-myristate-13-acetate (PMA) was used to construct a classic neutrophil inflammation model that was used to observe the formation of NETs in vitro. We studied the effect of irisin on NETs formation and its regulation mechanism. Subsequently, acute pancreatitis (AP) was used to verify the protective effect of irisin in vivo, which was an acute aseptic inflammatory response disease model closely related to NETs. RESULTS: Our study found that addition of irisin significantly reduced the formation of NETs via regulation of the P38/MAPK pathway through integrin αVß5, which might be the one of key pathways in NETs formation, and which could theoretically offset the immunoregulatory effect of irisin. Systemic treatment with irisin reduced the severity of tissue damage common in the disease and inhibited the formation of NETs in pancreatic necrotic tissue of two classical AP mouse models. CONCLUSION: The findings confirmed for the first time that irisin could inhibit NETs formation and protect mice from pancreatic injury, which further elucidated the protective effect of exercise on acute inflammatory injury.

Bile acid metabolomics identifies chenodeoxycholic acid as a therapeutic agent for pancreatic necrosis.

Bile acids are altered and associated with prognosis in patients with acute pancreatitis (AP). Here, we conduct targeted metabolomic analyses to detect bile acids changes in patients during the acute (n = 326) and the recovery (n = 133) phases of AP, as well as in healthy controls (n = 60). Chenodeoxycholic acid (CDCA) decreases in the acute phase, increases in the recovery phase, and is associated with pancreatic necrosis. CDCA and its derivative obeticholic acid exhibit a protective effect against acinar cell injury in vitro and pancreatic necrosis in murine models, and RNA sequencing reveals that the oxidative phosphorylation pathway is mainly involved. Moreover, we find that overexpression of farnesoid X receptor (FXR, CDCA receptor) inhibits pancreatic necrosis, and interfering expression of FXR exhibits an opposite phenotype in mice. Our results possibly suggest that targeting CDCA is a potential strategy for the treatment of acinar cell necrosis in AP, but further verification is needed.

AKBA alleviates experimental pancreatitis by inhibiting oxidative stress in Macrophages through the Nrf2/HO-1 pathway.

BACKGROUND: Acute pancreatitis (AP) is an inflammatory condition of the pancreas characterized by oxidative stress and inflammation in its pathophysiology. Acetyl-11-keto-ß-boswellic acid (AKBA) is an active triterpenoid with antioxidant activity. This article seeks to assess the impact of AKBA on AP and investigate its underlying mechanisms. METHODS: AP was induced in wild-type, Lyz2+/cre Nrf2fl/fl mice and Pdx1+/cre Nrf2fl/fl mice by caerulein. Serum amylase and lipase levels, along with histological grading, were utilized to evaluate the severity of AP. Murine bone marrow-derived macrophages (BMDMs) were isolated, cultured, and polarized to the M1 subtype. Flow cytometry and ELISA were utilized to identify the macrophage phenotype. Alterations in oxidative stress damage and intracellular ROS were observed. Nrf2/HO-1 signaling pathways were also evaluated. RESULTS: In a caerulein-induced mouse model of AP, treatment with AKBA reduced blood amylase and lipase activity and ameliorated pancreatic tissue histological and pathological features. Furthermore, AKBA significantly mitigated oxidative stress-induced damage and induced the expression of Nrf2 and HO-1 protein. Additionally, by using conditional knockout mice (Lyz2+/cre Nrf2fl/fl and Pdx1+/cre Nrf2fl/fl mice), we verified that Nrf2 primarily functions in macrophages rather than acinar cells. In vitro, AKBA inhibits pro-inflammatory M1-subtype macrophage polarization and reduces ROS generation through Nrf2/HO-1 oxidative stress pathway. Moreover, the protective effects of AKBA against AP were abolished in myeloid-specific Nrf2-deficient mice and BMDMs. Molecular docking results revealed interactions between AKBA and Nrf2. CONCLUSION: Our results confirm that AKBA exerts protective effects against AP in mice by inhibiting oxidative stress in macrophages through the Nrf2/HO-1 Pathway.

Elevated serum HbA1c level, rather than previous history of diabetes, predicts the disease severity and clinical outcomes of acute pancreatitis.

INTRODUCTION: The aim of our study is to explore the value of serum glycosylated hemoglobin A1c (HbA1c) in disease severity and clinical outcomes of acute pancreatitis (AP). RESEARCH DESIGN AND METHODS: Patients with AP were included from January 2013 to December 2020, retrospectively, dividing into normal serum HbA1c level (N-HbA1c) group and high serum HbA1c level (H-HbA1c) group according to the criteria HbA1c <6.5%. We compared patient characteristics, biochemical parameters, disease severity, and clinical outcomes of patients with AP in two groups. Besides, we evaluated the efficacy of serum HbA1c to predict organ failure (OF) in AP patients by receiver operating curve (ROC). RESULTS: We included 441 patients with AP, including 247 patients in N-HbA1c group and 194 patients in H-HbA1c group. Serum HbA1c level was positively correlated with Atlanta classification, systemic inflammatory response syndrome, local complication, and OF (all p<0.05). Ranson, BISAP (bedside index of severity in acute pancreatitis), and CT severity index scores in patients with H-HbA1c were markedly higher than those in patients with N-HbA1c (all p<0.01). ROC showed that the best critical point for predicting the development of OF in AP with serum HbA1c is 7.05% (area under the ROC curve=0.79). Logistic regression analysis showed H-HbA1c was the independent risk factor for the development of OF in AP. Interestingly, in patients with presence history of diabetes and HbA1c <6.5%, the severity of AP was significantly lower than that in H-HbA1c group. Besides, there was no significant difference between with and without history of diabetes in N-HbA1c group. CONCLUSIONS: Generally known, diabetes is closely related to the development of AP, and strict control of blood glucose can improve the related complications. Thus, the level of glycemic control before the onset of AP (HbA1c as an indicator) is the key to poor prognosis of AP, rather than basic history of diabetes. Elevated serum HbA1c level can become the potential indicator for predicting the disease severity of AP.

Bidirectional Hybrid LSTM Based Recurrent Neural Network for Multi-view Stereo.

Recently, deep learning based multi-view stereo (MVS) networks have demonstrated their excellent performance on various benchmarks. In this paper, we present an effective and efficient recurrent neural network (RNN) for accurate and complete dense point cloud reconstruction. Instead of regularizing the cost volume via conventional 3D CNN or unidirectional RNN like previous attempts, we adopt a bidirectional hybrid Long Short-Term Memory (LSTM) based structure for cost volume regularization. The proposed bidirectional recurrent regularization is able to perceive full-space context information comparable to 3D CNNs while saving runtime memory. For post-processing, we introduce a visibility based approach for depth map refinement to obtain more accurate dense point clouds. Extensive experiments on DTU, Tanks and Temples and ETH3D datasets demonstrate that our method outperforms previous state-of-the-art MVS methods and exhibits high memory efficiency at runtime.

Causal relationship between gut microbiota and serum vitamin D: evidence from genetic correlation and Mendelian randomization study.

BACKGROUND: The gastrointestinal microbiota is emerging as an important mediator in intestinal metabolism, such as vitamin D absorption. METHODS: To elucidate the causality of microbiota and vitamin D, we used linkage disequilibrium score (LDSC) regression and two-sample Mendelian randomization (MR) methods with largest genome-wide association study (GWAS) summary statistics to identify specific taxa that are linked to serum 25-hydroxyvitamin D (25(OH)D). RESULTS: We found that Ruminiclostridium9 was significantly genetically correlated with 25(OH)D at nominal significance (rg = 0.43, P = 0.04). Applying the inverse variance weighted (IVW) method, we identified that doubling the genetic liability of abundance of Erysipelotrichia, Erysipelotrichaceae and Erysipelotrichales reduced the concentration of 25(OH)D by 0.06 standard deviation (SD) (ßIVW = -0.06, s.e. = 0.01, P = 1.48 × 10-6, PFDR = 1.93 × 10-4) and, in turn, one SD increment in genetically determined serum 25(OH)D caused a 0.16 SD decrease in the relative abundance of Phascolarctobacterium (ßIVW = -0.16, s.e. = 0.04, P = 2.48 × 10-4, PFDR = 0.02) after removing pleiotropic instruments and outliers. Moreover, four MR methods were also used to evaluate causality, the results of which supported these findings. Leave-one-out analyses showed that the results were robust with regard to alterations in the single nucleotide polymorphisms (SNPs) we selected. CONCLUSIONS: In conclusion, our results support the hypothesis that the gut microbiota mediates the absorption of serum vitamin D supplementation and interacts with it closely. These microbiota are potential therapeutic targets for promoting serum vitamin D homeostasis.