Integrative multiomics profiling of passion fruit reveals the genetic basis for fruit color and aroma.

Passion fruit (Passiflora edulis) possesses a complex aroma and is widely grown in tropical and subtropical areas. Here, we conducted the de novo assembly, annotation, and comparison of PPF (P. edulis Sims) and YPF (P. edulis f. flavicarpa) reference genomes using PacBio, Illumina, and Hi-C technologies. Notably, we discovered evidence of recent whole-genome duplication events in P. edulis genomes. Comparative analysis revealed 7.6∼8.1 million single nucleotide polymorphisms, 1 million insertions/deletions, and over 142 Mb presence/absence variations among different P. edulis genomes. During the ripening of yellow passion fruit, metabolites related to flavor, aroma, and color were substantially accumulated or changed. Through joint analysis of genomic variations, differentially expressed genes, and accumulated metabolites, we explored candidate genes associated with flavor, aroma, and color distinctions. Flavonoid biosynthesis pathways, anthocyanin biosynthesis pathways, and related metabolites are pivotal factors affecting the coloration of passion fruit, and terpenoid metabolites accumulated more in PPF. Finally, by heterologous expression in yeast (Saccharomyces cerevisiae), we functionally characterized 12 terpene synthases. Our findings revealed that certain TPS homologs in both YPF and PPF varieties produce identical terpene products, while others yield distinct compounds or even lose their functionality. These discoveries revealed the genetic and metabolic basis of unique characteristics in aroma and flavor between the 2 passion fruit varieties. This study provides resources for better understanding the genome architecture and accelerating genetic improvement of passion fruits.

CircPIAS1 promotes hepatocellular carcinoma progression by inhibiting ferroptosis via the miR-455-3p/NUPR1/FTH1 axis.

BACKGROUND: The role of circRNAs in hepatocellular carcinoma (HCC) progression remains unclear. CircPIAS1 (circBase ID: hsa_circ_0007088) was identified as overexpressed in HCC cases through bioinformatics analysis. This study aimed to investigate the oncogenic properties and mechanisms of circPIAS1 in HCC development. METHODS: Functional analyses were conducted to assess circPIAS1's impact on HCC cell proliferation, migration, and ferroptosis. Xenograft mouse models were employed to evaluate circPIAS1's effects on tumor growth and pulmonary metastasis in vivo. Bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays were utilized to elucidate the molecular pathways influenced by circPIAS1. Additional techniques, including RNA pulldown, fluorescence in situ hybridization (FISH), chromatin immunoprecipitation (ChIP), qPCR, and western blotting, were used to further explore the underlying mechanisms. RESULTS: CircPIAS1 expression was elevated in HCC tissues and cells. Silencing circPIAS1 suppressed HCC cell proliferation and migration both in vitro and in vivo. Mechanically, circPIAS1 overexpression inhibited ferroptosis by competitively binding to miR-455-3p, leading to upregulation of Nuclear Protein 1 (NUPR1). Furthermore, NUPR1 promoted FTH1 transcription, enhancing iron storage in HCC cells and conferring resistance to ferroptosis. Treatment with ZZW-115, an NUPR1 inhibitor, reversed the tumor-promoting effects of circPIAS1 and sensitized HCC cells to lenvatinib. CONCLUSION: This study highlights the critical role of circPIAS1 in HCC progression through modulation of ferroptosis. Targeting the circPIAS1/miR-455-3p/NUPR1/FTH1 regulatory axis may represent a promising therapeutic strategy for HCC.

Mesenchymal Stem Cells Promote Polarization of M2 Macrophages in Mice with Acute-On-Chronic Liver Failure via Mertk/JAK1/STAT6 Signaling.

Acute-on-chronic liver failure (ACLF) is a severe disease with a high mortality. Macrophage-related inflammation plays a crucial role in ACLF development. Mesenchymal stem cells (MSCs) treatment was demonstrated to be beneficial in ACLF in our previous study; however, the underlying mechanisms remain unknown. Therefore, mouse bone marrow-derived MSCs were used to treat an ACLF mouse model or cocultured with RAW264.7/J774A.1 macrophages that were stimulated with LPS. Histological and serological parameters and survival were analyzed to evaluate efficacy. We detected changes of Mer tyrosine kinase (Mertk), JAK1/STAT6, inflammatory cytokines, and markers of macrophage polarization in vitro and in vivo. In ACLF mice, MSCs improved liver function and 48-h survival of ACLF mice and alleviated inflammatory injury by promoting M2 macrophage polarization and elevated Mertk expression levels in macrophages. This is significant, as Mertk regulates M2 macrophage polarization via the JAK1/STAT6 signaling pathway.

Mesenchymal stem cell-regulated miRNA-mRNA landscape in acute-on-chronic liver failure.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a major challenge in the field of hepatology. While mesenchymal stem cell (MSC) therapy can improve the prognosis of patients with ACLF, the molecular mechanisms through which MSCs attenuate ACLF remain poorly understood. We performed global miRNA and mRNA expression profiling via next-generation sequencing of liver tissues from MSC-treated ACLF mice to identify important signaling pathways and major factors implicated in ACLF alleviation by MSCs. METHODS: Carbon tetrachloride-induced ACLF mice were treated with saline or mouse bone marrow-derived MSCs. Mouse livers were subjected to miRNA and mRNA sequencing. Related signal transduction pathways were obtained through Gene Set Enrichment Analysis. Functional enrichment, protein-protein interaction, and immune infiltration analyses were performed for the differentially expressed miRNA target genes (DETs). Hub miRNA and mRNA associated with liver injury were analyzed using LASSO regression. The expression levels of hub genes were subjected to Pearson's correlation analysis and verified using RT-qPCR. The biological functions of hub genes were verified in vitro. RESULTS: The tricarboxylic acid cycle and peroxisome proliferator-activated receptor pathways were activated in the MSC-treated groups. The proportions of liver-infiltrating NK resting cells, M2 macrophages, follicular helper T cells, and other immune cells were altered after MSC treatment. The expression levels of six miRNAs and 10 transcripts correlated with the degree of liver injury. miR-27a-5p was downregulated in the mouse liver after MSC treatment, while its target gene E2f2 was upregulated. miR-27a-5p inhibited E2F2 expression, suppressed G1/S phase transition and proliferation of hepatocytes, in addition to promoting their apoptosis. CONCLUSIONS: This is the first comprehensive analysis of miRNA and mRNA expression in the liver tissue of ACLF mice after MSC treatment. The results revealed global changes in hepatic pathways and immune subpopulations. The miR-27a-5p/E2F2 axis emerged as a central regulator of the MSC-induced attenuation of ACLF. The current findings improve our understanding of the molecular mechanisms through which MSCs alleviate ACLF.

Systematic characterization and prediction of coenzyme A-associated proteins using sequence and network information.

Coenzyme A-associated proteins (CAPs) are a category of functionally important proteins involved in multiple biological processes through interactions with coenzyme A (CoA). To date, unfortunately, the specific differences between CAPs and other proteins have yet to be systemically investigated. Moreover, there are no computational methods that can be used specifically to predict these proteins. Herein, we characterized CAPs from multifaceted viewpoints and revealed their specific preferences. Compared with other proteins, CAPs were more likely to possess binding regions for CoA and its derivatives, were evolutionarily highly conserved, exhibited ordered and hydrophobic structural conformations, and tended to be densely located in protein-protein interaction networks. Based on these biological insights, we built seven classifiers using predicted CoA-binding residue distributions, word embedding vectors, remote homolog numbers, evolutionary conservation, amino acid composition, predicted structural features and network properties. These classifiers could effectively identify CAPs in Homo sapiens, Mus musculus and Arabidopsis thaliana. The complementarity among the individual classifiers prompted us to build a two-layer stacking model named CAPE for improving prediction performance. We applied CAPE to identify some high-confidence candidates in the three species, which were tightly associated with the known functions of CAPs. Finally, we extended our algorithm to cross-species prediction, thereby developing a generic CAP prediction model. In summary, this work provides a comprehensive survey and an effective predictor for CAPs, which can help uncover the interplay between CoA and functionally relevant proteins.

Analytical method for calculating internal stray radiation from an IR spectrometer based on the view factor.

Optomechanical components such as the lens barrels and frames of IR spectrometers produce strong internal stray radiation, which reduces the instrument's SNR and dynamic range. An IR internal stray radiation calculation method based on an analytical model of the view factor is proposed. The mathematical model of the view factor calculation method of typical optomechanical components is established. For any IR optical systems, the internal stray radiation can be quickly and accurately calculated by adjusting the coordinate systems in the calculation method. Based on the proposed method, the internal stray radiation of a double-pass long-wave IR spectrometer was calculated. The calculation results are consistent with the simulation results. The RMS value of the relative error between the calculated value and the simulated value is around 11%. To verify the proposed method, an experiment was conducted to test the internal stray radiation of the long-wave IR spectrometer. The internal stray radiation test results agree with the calculated and simulated results, and the relative error between the test results and the calculation results is within 9%.

Tooth autotransplantation: An umbrella review.

Tooth autotransplantation is a versatile procedure with several clinical applications among patients across different age groups. The success of this procedure depends on multiple factors. Despite the wealth of studies available, no single primary study or systematic review is able to report on every factor affecting the outcomes of autotransplantation. The aims of this umbrella review were to evaluate treatment-related and patient-related outcomes of autotransplantation and to assess the pre-, peri- or post-operative factors that could affect these. An umbrella review was conducted according to the PRISMA statement. A literature search of five databases was performed up to 25 September 2022. Systematic Reviews (SR) with and without meta-analysis evaluating autotransplantation were included. Calibration among reviewers was carried out prior to study selection, data extraction and Risk of Bias (RoB) assessment. Study overlap was calculated using corrected covered area. Meta-meta-analysis (MMA) was performed for suitable SRs. The AMSTAR 2 critical appraisal tool was used to evaluate the quality of evidence. Seventeen SRs met the inclusion criteria. Only two SRs were suitable for conduct of MMA on autotransplantation of open apex teeth. The 5-year and 10-year survival rates were >95%. A narrative summary on factors that could affect autotransplantation outcomes and comparisons of autotransplantation to other treatment options were reported. Five SRs were rated as 'low quality' and 12 SRs were rated as 'critically low quality' in the AMSTAR 2 RoB assessment. In order to facilitate a more homogenous pool of data for subsequent meta-analysis, an Autotransplantation Outcome Index was also proposed to standardise the definition of outcomes. Autotransplantation of teeth with open apices have a high survival rate. Future studies should standardise the reporting of clinical and radiographic findings, as well as the definition of outcomes.

Tooth autotransplantation with 3D-printed replicas as part of interdisciplinary management of children and adolescents: Two case reports.

The management of missing teeth as a result of dental trauma or associated with hypodontia in children and adolescents presents as a clinical challenge for the dental team. One of the options that is regaining popularity is dental autotransplantation. To improve autotransplantation outcomes, careful interdisciplinary planning, surgical simulation using cone beam computed tomography images and three-dimensional-printed teeth replicas should be undertaken for presurgical preparation. This case report showcases two applications of autotransplantation, with emphasis on interdisciplinary management, presurgical preparation and postsurgical orthodontic and aesthetic management to deliver a good long-term, sustainable, biological outcome, as a part of a comprehensive rehabilitation treatment plan in children.

Outcomes of preformed metal crowns placed with the conventional and Hall techniques: A systematic review and meta-analysis.

BACKGROUND: Preformed metal crowns (PMCs) have been used to restore carious primary molars and have a high success and survival rate. There are two methods currently employed for PMC placement - the conventional technique (CT) and Hall technique (HT). AIM: This systematic review aims to compare the outcomes of PMCs placed using the CT and HT. DESIGN: This systematic review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. A literature search of five databases was performed up to 23 August 2022. Clinical studies comparing carious primary molars restored with PMCs using either technique with a minimum 12-month follow-up were included. Risk of bias (RoB) assessment was performed using the National Institutes of Health Quality Assessment tool. RESULTS: Five articles met the inclusion criteria, and four were included for meta-analysis. The 12- and 24-month success and survival rates were above 85% for both groups, with no significant differences shown at 12 and 24 months. The HT requires a shorter treatment duration, is more cost-effective and has a high level of acceptability among parents when compared to the CT. Four articles were rated fair, and one article was rated good in the RoB assessment. CONCLUSION: Greater consideration may be given towards using the HT as part of standard treatment procedures in managing carious primary molars. Future studies should standardise reporting of outcomes to facilitate a more homogeneous pool of data for future meta-analysis.

The impact of serum thyroid-stimulation hormone levels on the outcome of hepatitis B virus related acute-on-chronic liver failure: an observational study.

BACKGROUND: Thyroid dysfunction has been reported in severe liver diseases. The aim of this study was to analyze the impact of serum thyroid-stimulation hormone (TSH) levels on the prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). METHODS: This retrospective cohort study included 1,862 patients with HBV-related ACLF. Risk factors associated with 30-day and 90-day survival, hazard ratios (HRs), and 95% confidence intervals (CIs) for TSH were estimated using Cox proportional hazards regression. The Area Under the ROC curve (AUROC) analysis was carried out, and the cut-off values were calculated. After grouping by the cut-off value, survival was compared between the groups using the log-rank test. This study data is from the "Survival Cohort Study (SCS)", which has been registered at ClinicalTrials.gov (NCT03992898). RESULTS: Multivariate analysis indicated that an elevated TSH level was a highly significant predictor for 30-day survival (HR = 0.743, 95% CI: 0.629-0.878, P < 0.001) and 90-day survival (HR = 0.807, 95% CI: 0.717-0.909, P < 0.001). The AUROC of TSH level for 30-day and 90-day mortality were 0.655 and 0.620, respectively, with the same best cut-off values of 0.261 µIU/mL. Log-rank test showed that the group with higher TSH level had higher 30-day (78.5%, 95% CI: 76.1%-80.9% vs. 56.9%, 95% CI: 53.4%-60.4%; P < 0.001) and 90-day survival rate (61.5%, 95% CI: 58.6%-64.4% vs. 42.8%, 95% CI: 39.3%-46.3%; P < 0.001). Similar findings were observed in subgroups analysis. After adjusting for age and other risk factors, the higher level of TSH remained associated with 30-day survival (HR = 0.602, 95% CI: 0.502-0.721, P < 0.001) and 90-day survival (HR = 0.704, 95% CI, 0.609-0.814, P < 0.001). CONCLUSIONS: Serum TSH level significantly correlate with HBV-related ACLF patients' survival and may be of value for predicting 30-day and 90-day survival of patients with HBV-related ACLF.

Risk factors for underlying comorbidities and complications in patients with hepatitis B virus-related acute-on-chronic liver failure.

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a severe and life-threatening complication, characterised by multi-organ failure and high short-term mortality. However, there is limited information on the impact of various comorbidities on HBV-ACLF in a large population. This study aimed to investigate the relationship between comorbidities, complications and mortality. In this retrospective observational study, we identified 2166 cases of HBV-ACLF hospitalised from January 2010 to March 2018. Demographic data from the patients, medical history, treatment, laboratory indices, comorbidities and complications were collected. The mortality rate in our study group was 47.37%. Type 2 diabetes mellitus was the most common comorbidity, followed by alcoholic liver disease. Spontaneous bacterial peritonitis, pneumonia and hepatic encephalopathy (HE) were common in these patients. Diabetes mellitus and hyperthyroidism are risk factors for death within 90 days, together with gastrointestinal bleeding and HE at admission, HE and hepatorenal syndrome during hospitalisation. Knowledge of risk factors can help identify HBV-ACLF patients with a poor prognosis for HBV-ACLF with comorbidities and complications.

Comprehensive design analysis and verification of space-based short-wave infrared coded spectrometer via curved prism dispersion.

The spaceborne dispersive spectrometer is widely used in environmental, resource, and ocean observations. The coded spectrometer has higher energy advantages than the dispersion spectrometer, so it has great application prospects. In the current study, we developed an off-axis short-wave infrared coded optical system (SICOS) based on curved prism dispersion, and we further explored the design and optimization of the SICOS structure. Finite element analyses of a space-based short-wave infrared coded spectrometer based on curved prism dispersion (SSICS-CPD), including static simulation, modal analysis, sinusoidal vibration mechanical analysis, and random vibration mechanical analysis, were carried out. Simulation results showed that the SICOS support structure had excellent mechanical and thermal stability. As off-axis optical systems cannot meet the requirements of optical position accuracy through centering processing, a point source microscope and three-coordinate measuring machines were employed to complete the high-precision and rapid assembly of the SSICS-CPD. In addition, verification tests of surface shape error, stress relief, random vibration, and optical design parameters were carried out to validate the high stability and imaging performance of the SSICS-CPD. Results showed that the average modulation transfer function in the full field was 0.43 at 16.67 lp/mm, the spectral smile was <0.2 pixels, and the spectral keystone was <0.1 pixels. The design, analysis, assembly, and verification of the SSICS-CPD provide a useful reference for the development of other spaceborne prism dispersion spectrometers.

Pharmacokinetic comparison of four arbidol hydrochloride preparations in beagle dogs.

This study aimed to compare the pharmacokinetic properties of four preparations (dispersible tablets, ordinary tablets, capsules and granules) of arbidol hydrochloride, a broad-spectrum antiviral drug, in beagle dogs. Briefly, a single dose of 100 mg of the four preparations of arbidol hydrochloride was orally administered to dogs; blood was then collected from the veins of the foreleg at different times after administration to prepare plasma samples. The plasma concentration of arbidol hydrochloride was measured using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results showed that when orally administered with dispersible tablets, ordinary tablets, capsules and granules suspended with water, there were no significant differences in the pharmacokinetic parameters (including peak time, peak concentration, elimination half-life, area under the curve (AUC0-t ), and mean retention time) of arbidol hydrochloride. However, in the case of the dispersible tablets, the pharmacokinetics of arbidol hydrochloride was significantly affected by the mode of administration. Compared with direct feeding, peak time [0.50 (0.13, 0.50) vs. 1.00 (0.50, 2.00)] was significantly shortened (P = 0.033) and the AUC0-48 h (8726.5 ± 2509.3 vs. 3650.8 ± 1536.9 ng h/ml) was significantly increased (P = 0.012) when the dispersible tablets were orally administered as water dispersion. In conclusion, the pharmacokinetics of four preparations of arbidol hydrochloride were not significant different in beagle dogs. However, compared with direct feeding, the absorption of arbidol hydrochloride was faster and the bioavailability was better when the dispersible tablets were orally administered as water dispersion.

Direct Oxygen Transfer from H2 O to Cyclooctene over Electron-Rich RuO2 Nanocrystals for Epoxidation and Hydrogen Evolution.

Production of more than 20 million tons of epoxides per year from olefins suffers from low atom economy due to the use of oxidants and complex catalysts with unsatisfactory selectivity, leading to huge environmental and economic costs. We present a proof-of-concept application of electron-rich RuO2 nanocrystals to boost the highly selective epoxidation of cyclooctene via direct oxygen transfer from water as the sole oxygen source under mild conditions. The enhanced electron enrichment of RuO2 nanocrystals via the Schottky effect with nitrogen-doped carbons largely promotes the capture and activation of cyclooctene to give a high turnover frequency (260 h-1 ) of cyclooctene oxide, far surpassing the reported values (<20 h-1 ) of benchmarked catalysts at room temperature with oxidants. Our electron-rich RuO2 electrocatalysts enable efficient and durable hydrogen production (Faradaic efficiency >90 %) on the cathode without impacting on the selectivity to epoxide (>99 %) on the anode.

Design analysis and test verification of a rigid-flexible, dual-mode coupling support structure for space-based rectangular curved prisms.

In view of the functional requirements of high reliability and stability support of optical components of space remote sensors, a rigid-flexible, dual-mode coupling support structure for space-based rectangular curved prisms (SRCPs) was designed. In-depth studies of the support principle and engineering realization of the SRCPs and optimization of the flexible adhesive structure were performed. Static and dynamic simulations were conducted on the mirror subassembly by means of finite element analysis, and test verification was also performed. The tests revealed that the surface shape error of the mirror subassembly after mechanical testing was 0.021λ, the displacement of the mirror body was 0.008 mm, the inclination angle was ∼0.8'', the mass of the mirror subassembly was 4.79 kg, the fundamental frequency was 283 Hz, and the maximum amplification of the total rms acceleration was 4.37. All indexes were superior to those of the design requirements. On this basis, bonding tests and mechanical tests of a rectangular curved prism reflector, a rectangular curved prism, and a rectangular plane reflector employing this proposed support structure were continued. The test results verified the reliability, stability, and universal applicability of the proposed rigid-flexible, dual-mode peripheral bonding support structure.

Do betel quid and areca nut chewing deteriorate prognosis of oral cancer? A systematic review, meta-analysis, and research agenda.

OBJECTIVE: To explore the correlations between the habit of betel quid and areca nut (BQ-AN) chewing and the prognosis of oral cancer (OC). METHODS: We performed a systematic review and meta-analysis to clarify this issue. Data searches were performed using PubMed, Web of Science, Epistemonikos, and Embase databases through November 2019. The primary outcome was the difference in the prognosis of OC between BQ-AN chewers and non-chewers, measured in terms of 5-year overall survival (OS) and 5-year disease-specific survival (DSS) log (HR) reported in articles. The pooled HR with 95% CI of 5-year OS and 5-year DSS was calculated using a fixed-effects model. RESULTS: Ten articles with eleven OS or DSS survival studies (one of the articles contained two studies), which were published between 2003 and 2017, were eligible for inclusion in the present study. All the 11 studies were observational studies, among which 10 were retrospective and 1 was prospective. One study measured both OS and DSS. Eight studies, with a total of 2,761 patients, used 5-year OS as the primary endpoint and four studies, with a total of 2,551 patients, used 5-year DSS. Overall, the pooled HR evaluating BQ-AN chewers was 1.26 (95% CI: 1.09-1.46) for 5-year OS and 1.40 (95% CI: 1.15-1.70) for 5-year DSS, compared with non-chewers. There was a significant association between BQ-AN chewing and OC survival. CONCLUSIONS: Betel quid and areca nut chewing is significantly associated with poor prognosis in patients with OC.

Quantifying the RNA cap epitranscriptome reveals novel caps in cellular and viral RNA.

Chemical modification of transcripts with 5' caps occurs in all organisms. Here, we report a systems-level mass spectrometry-based technique, CapQuant, for quantitative analysis of an organism's cap epitranscriptome. The method was piloted with 21 canonical caps-m7GpppN, m7GpppNm, GpppN, GpppNm, and m2,2,7GpppG-and 5 'metabolite' caps-NAD, FAD, UDP-Glc, UDP-GlcNAc, and dpCoA. Applying CapQuant to RNA from purified dengue virus, Escherichia coli, yeast, mouse tissues, and human cells, we discovered new cap structures in humans and mice (FAD, UDP-Glc, UDP-GlcNAc, and m7Gpppm6A), cell- and tissue-specific variations in cap methylation, and high proportions of caps lacking 2'-O-methylation (m7Gpppm6A in mammals, m7GpppA in dengue virus). While substantial Dimroth-induced loss of m1A and m1Am arose with specific RNA processing conditions, human lymphoblast cells showed no detectable m1A or m1Am in caps. CapQuant accurately captured the preference for purine nucleotides at eukaryotic transcription start sites and the correlation between metabolite levels and metabolite caps.

MTHFD1L as a folate cycle enzyme correlates with prognostic outcome and its knockdown impairs cell invasive behaviors in osteosarcoma via mediating the AKT/mTOR pathway.

Osteosarcoma (OS) is the most frequent primary malignancy initially in bone with multiple genomic aberrations. Methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) is linked with the progression of diverse tumors. However, its function in OS is not understood completely. The expression pattern and prognostic significance of MTHFD1L in OS tissues were analyzed based on GEO database. The expression level of MTHFD1L in OS cell lines was explored by qRT-PCR. The cell proliferation, colony formation ability, invasion as well as migration in OS cells after MTHFD1L knockdown were determined using cell counting kit 8 (CCK-8) assay, colony formation and transwell methods. GSEA analysis was performed to predict the underlying mechanisms of MTHFD1L in OS development. Furthermore, the western blot was utilized to study the influence of MTHFD1L on AKT/mTOR pathway. Our results indicated that MTHFD1L expression was significantly up-regulated in OS tissues and cells compared with normal tissues and cells. High expression of MTHFD1L could lead to poor prognosis of OS patients. Cell proliferation, colony formation ability, migration and invasion were blocked because of reduced MTHFD1L in vitro. Moreover, cell cycle and AKT/mTOR pathway were all associated with MTHFD1L expression. In conclusion, the findings revealed that MTHFD1L might promote the development of OS via mediating cell cycle and AKT/mTOR pathway, indicating that MTHFD1L might act as a promising therapeutic target for OS treatment.

Associations between nephrolithiasis and diabetes mellitus, hypertension and gallstones: A meta-analysis of cohort studies.

AIM: To review and clarify the strengths and directions of associations between nephrolithiasis and hypertension (HTN), diabetes mellitus (DM) and gallstones (GS) given the inconsistent results reported in cohort studies. METHODS: Relevant literature was searched in PubMed and EMBASE from inception to July 2019, for cohort studies that examined the relationships between kidney stones and these three diseases among adults. Pooled relative risks (RRs) were calculated by maximally adjusted risk estimates using a random effect model. Subgroup analysis, meta-regression and sensitivity analysis were conducted whenever appropriate. RESULTS: Of 3537 papers, 21 articles with each including 1 to 3 cohorts were identified. In this meta-analysis, nephrolithiasis was reciprocally linked to HTN, DM and GS. Kidney stones were significantly associated with 31%, 33% and 46% higher risks of incident HTN, DM and GS whereas GS was associated with a significantly higher risk of nephrolithiasis (RR: 1.49; 95% CI, 1.28-1.73), followed by HTN (RR: 1.30; 95% CI, 1.11-1.52) and DM (RR: 1.18; 95% CI, 1.07-1.29). Also, females with DM (RR: 1.29; 95% CI, 1.08-1.55) were more likely to develop kidney stones than diabetic male patients (RR: 0.91; 95% CI, 0.75-1.10). CONCLUSION: Although additional studies are needed to confirm these findings and elucidate the mechanisms, this study revealed possible bidirectional associations between nephrolithiasis and HTN, diabetes and GS, which reinforced the notion of nephrolithiasis as a systemic disease that requires comprehensive investigations.

Dietary and lifestyle factors for primary prevention of nephrolithiasis: a systematic review and meta-analysis.

BACKGROUND: Dietary and lifestyle factors may play an important role in the increasing prevalence of nephrolithiasis. We aimed to review and quantify the associations between lifestyle factors and incident nephrolithiasis and suggest lifestyle changes for the primary prevention of nephrolithiasis. METHODS: PubMed, EMBASE, and Cochrane Library were searched up to May 2019, for observational studies and randomized controlled trials (RCTs) that assessed modifiable lifestyle factors and risk of nephrolithiasis in adults. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were computed using a random effects model. The I2 statistic was employed to evaluate heterogeneity. Subgroup analysis, sensitivity analysis and meta-regression were also conducted whenever possible. RESULTS: Fifty relevant articles with 1,322,133 participants and 21,030 cases in total were identified. Prominent risk factors for incident stones were body mass index (1.39,1.27-1.52), dietary sodium (1.38, 1.21-1.56), fructose, meat, animal protein, and soda. In contrast, protective factors included fluid intake (0.55, 0.51-0.60), a Dietary Approaches to Stop Hypertension (DASH) style diet (0.69, 0.64-0.75), alcohol (0.69, 0.56-0.85), water, coffee, tea, vegetables, fruits, dietary fiber, dietary calcium (0.83, 0.76-0.90), and potassium. Vitamin D (1.22, 1.01-1.49) and calcium (1.16, 1.00-1.35) supplementation alone increased the risk of stones in meta-analyses of observational studies, but not in RCTs, where the cosupplementation conferred significant risk. CONCLUSIONS: Several modifiable factors, notably fluid intake, dietary patterns, and obesity, were significantly associated with nephrolithiasis. Long-term RCTs are required to investigate the cost-effectiveness of dietary patterns for stone prevention. The independent and combined effects of vitamin D and calcium supplementation on nephrolithiasis need further elucidation.