Construction of an artificial phosphoketolase pathway that efficiently catabolizes multiple carbon sources to acetyl-CoA.

The canonical glycolysis pathway is responsible for converting glucose into 2 molecules of acetyl-coenzyme A (acetyl-CoA) through a cascade of 11 biochemical reactions. Here, we have designed and constructed an artificial phosphoketolase (APK) pathway, which consists of only 3 types of biochemical reactions. The core enzyme in this pathway is phosphoketolase, while phosphatase and isomerase act as auxiliary enzymes. The APK pathway has the potential to achieve a 100% carbon yield to acetyl-CoA from any monosaccharide by integrating a one-carbon condensation reaction. We tested the APK pathway in vitro, demonstrating that it could efficiently catabolize typical C1-C6 carbohydrates to acetyl-CoA with yields ranging from 83% to 95%. Furthermore, we engineered Escherichia coli stain capable of growth utilizing APK pathway when glycerol act as a carbon source. This novel catabolic pathway holds promising route for future biomanufacturing and offering a stoichiometric production platform using multiple carbon sources.

Identification of causal metabolites related to multiple autoimmune diseases.

Observational studies provide evidence that metabolites may be involved in the development of autoimmune diseases (ADs), but whether it is causal is still unknown. Based on the large-scale genome-wide association studies (GWAS) summary statistics, we performed two-sample Mendelian randomization (MR) to evaluate the causal associations between human blood metabolites and multiple ADs, which were inflammatory bowel disease (IBD), ulcerative colitis (UC), crohns disease (CD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), multiple sclerosis (MS), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). After Bonferroni adjustment, we identified 6 causal features of metabolites, i.e., glycerol 2-phosphate for T1D, hexadecanedioate, phenylacetylglutamine and laurylcarnitine for RA, glycine and arachidonate (20:4n6) for CD. Comprehensive sensitive analysis was further performed to validate the robustness of associations. We also observed some overlaps of metabolites among different ADs, implying similar or shared underlying mechanisms in such pathogenic processes. Multivariable MR analysis was then conducted to avoid potential pleiotropic effect of other complex traits. After controlling for several common traits, multivariable MR analysis ruled out most of potential pleiotropic effects and validated independence of identified metabolites. Finally, metabolic pathway analysis was performed based on suggestive metabolites for each AD respectively and a total of seven metabolic pathways were identified. In conclusion, this study provided novel insights into investigating causal role of blood metabolites in development of multiple ADs through a comprehensive genetic pathway.

Rheumatoid arthritis and osteoporosis: shared genetic effect, pleiotropy and causality.

Rheumatoid arthritis (RA) is associated with increased localized and generalized bone loss, but the complex genetic mechanism between them is still unknown. By leveraging large-scale genome-wide association studies summary statistics and individual-level datasets (i.e. UK Biobank), a series of genetic approaches were conducted. Linkage disequilibrium score regression reveals a shared genetic correlation between RA and estimated bone mineral density (eBMD) (rg = -0.059, P = 0.005). The PLACO analysis has identified 74 lead (8 novel) pleiotropic loci that could be mapped to 99 genes, the genetic functions of which reveal the possible mechanism underlying RA and osteoporosis. In European, genetic risk score (GRS) and comprehensive Mendelian randomization (MR) were utilized to evaluate the causal association between RA and osteoporosis in European and Asian. The increase in GRS of RA could lead to a decrease of eBMD (beta = -0.008, P = 3.77E-6) and a higher risk of facture [odds ratio (OR) = 1.012, P = 0.044]. MR analysis identified that genetically determined RA was causally associated with eBMD (beta = -0.021, P = 4.14E-05) and fracture risk (OR = 1.036, P = 0.004). Similar results were also observed in Asian that osteoporosis risk could be causally increased by RA (OR = 1.130, P = 1.04E-03) as well as antibodies against citrullinated proteins-positive RA (OR = 1.083, P = 0.015). Overall, our study reveals complex genetic mechanism between RA and osteoporosis and provides strong evidence for crucial role of RA in pathogenesis of osteoporosis.

Immune checkpoint inhibitor-associated acute kidney injury in patients with cancer: a systematic review and meta-analysis of risk factors.

BACKGROUND: As a novel antineoplastic drug, immune checkpoint inhibitors (ICIs) are associated with a spectrum of autoimmune-related side effects, including acute kidney injury (AKI). Understanding the risk factors for immune-associated acute kidney injury will inform future symptom management measures to reduce this risk. This study aims to identify the risk factors for ICIs-AKI in cancer patients through a systematic review and meta-analysis. METHODS: The systematic search was conducted in The Cochrane Library, Pubmed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP Database. The related studies published since the establishment of the database to Aug 22, 2022, were screened, data was extracted following the inclusion and exclusion criteria, and the quality of the selected studies was assessed by Newcastle-Ottawa Scale (NOS). The above was performed independently by the two reviewers. The estimated pooled odds ratios (ORs) for risk factors of developing ICIs-AKI were conducted by random-effects meta-analysis. RESULTS: A total of 8 publications, including 5267 patients, were included. Meta-analysis results showed that extrarenal immune-related adverse events (irAEs), therapy with the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), male, hypertension, pre-existent use of a diuretic, and a proton pump inhibitor (PPI) were significantly correlated to ICIs-AKI. CONCLUSIONS: We identified extrarenal irAEs, CTLA-4 treatments, males, hypertension, previous use of diuretics, and PPIs are essential predictors of ICIs-AKI. These findings are helpful for healthcare providers to monitor ICIs-AKI for management and timely interventions.

Two-stage ligament reconstruction with remnant preservation as treatment of knee dislocation.

OBJECTIVE: The purpose of this study was to evaluate the clinical outcomes of two-stage reconstruction (peripheral reconstruction in phase I and central anterior cruciate ligament (ACL) / posterior cruciate ligament (PCL) reconstruction in phase II) with remnant preservation for patients with knee dislocation. METHODS: A total of 70 patients (10 IIIM, 17 IIIL, and 43 IV) with knee dislocation were randomly divided into the remnant-preserved group and the simple reconstruction group. Patients underwent two-stage reconstruction, including the reconstruction of collateral ligament in phase I and the reconstruction of ACL/PCL in phase II (12 weeks after phase I). Grafts were harvested from the semitendinosus and gracilis tendons from both lower limbs. After the surgery, the joint flexion and extension, bone tunnel and ligament healing, and joint stability were evaluated. RESULTS: After the surgery, the lateral stability recovered in all patients, and X-ray revealed a good position of bone tunnel. Follow-up was performed at 12 months postoperatively and ranged from 24 to 91 months. At the final follow-up, knee flexion angle, IKDC, Lysholm, and Tegner scores were all higher in both groups compared to the preoperative period. Notably, the remnant-preserved group showed superior results in these parameters compared to the simple reconstruction group. There was statistical significance between the two groups in terms of the Lachman test. CONCLUSION: The knee function was well recovered after two-stage ligament reconstruction with remnant preservation.

Relationship between indwelling site and peripheral venous catheter-related complications in adult hospitalized patients: A systematic review and meta-analysis.

AIMS AND OBJECTIVES: This systematic review and meta-analysis aimed to compare the incidence of PVC-related complications between catheterisation in the forearm and back of the hand in adult patients. BACKGROUND: A peripheral intravenous catheter (PVC) is often inserted as part of care during patients' hospitalisation. The catheter is typically inserted in the forearm or at the back of the hand in usual practice. Studies have not yet reached a consensus on the optimal insertion site in any clinical setting. DESIGN: We performed a systematic review and meta-analysis based on PRISMA guidelines. METHODS: We searched the following electronic databases: PubMed, Cochrane Library, Embase, and CINAHL. Randomised controlled trials, cohort studies, case-control studies and cross-sectional studies from inception to July 2021 reporting the incidence of PVC-related complications at the forearm and back of the hand were included. Fixed-effects models and random-effects models were used to derive the pooled risk ratios. RESULTS: Twenty-four studies involving 16562 PVCs met our inclusion criteria. The meta-analysis showed that compared with PVC placement in the back of the hand, placement in the forearm was associated with a higher incidence of total complications and infiltration/extravasation. However, the differences between the PVC indwelling sites were not significant (total complications: P = 0.43; phlebitis: P = 0.35; infiltration/extravasation: P = 0.51). Both incidence of total complications and infiltration/extravasation analyses showed high heterogeneity (total complications: I2  = 60%; infiltration/extravasation: I2  = 58%). CONCLUSION: Available evidence suggests that there is no significant difference between PVC placement in the forearm and at the back of the hand in terms of the incidence of complications, thus making both approaches suitable. RELEVANCE TO CLINICAL PRACTICE: For patients who need indwelling PVC, medical staff can choose the best indwelling site, and both forearm and back of the hand are suitable.

Siting MPAs for multiple protecting purposes by co-consideration of ecological importance and anthropogenic impacts.

The global marine ecosystem has been significantly altered by the combined effects of multiple anthropogenic impacts. Systematic planning of marine protected areas (MPAs) is of paramount importance in alleviating conflicts between humans and the sea. Existing approaches, however, merely integrate both ecological and anthropogenic factors for multiple conservation purposes. By combining the three main anthropogenic impact factors with two main ecological importance factors, this study used a GIS-based AHP-OWA method to identify different levels of priority protection for MPAs in Zhejiang, China. Our results proved that: 1) the multi-objective MPA siting issues can be addressed by the GIS-based AHP-OWA method through scenario simulation; 2) the best locations for MPAs are in the northeast, central, and southern marine areas of Zhejiang; 3) considering the trade-off degree, spatial conservation efficiency, and spatial heterogeneity, an optimized MPA siting scheme can be developed for decision-makers. The proposed MPA siting method and case study may provide an effective technical reference for solving regional marine spatial planning (MSP) issues in the future.

Individualized Whole Course Nutrition Management for Nasopharyngeal Carcinoma Patients Undergoing Radiotherapy.

BACKGROUND: Radiotherapy-induced oral mucositis (RIOM) is the most common toxicity associated with radiotherapy for nasopharyngeal carcinoma (NPC). Patients with RIOM become malnourished, which can affect the delivery and dose of radiotherapy. The value of personalizing nutrition recommendations for cancer prevention and management is increasingly recognized. To investigate the effect of individualized whole course nutrition management on nutritional status and the incidence and severity of RIOM in NPCs. METHODS: This retrospective study included 77 patients who were provided individualized whole course nutrition management during radiotherapy (RT) and a 1-month follow-up. Seventy-one patients were included in the control group. RESULTS: During radiotherapy, severity of RIOM was significantly lower in the intervention group. There were statistically significant differences in oral mucosa recovery time and nutritional status between the two groups (p < 0.05). CONCLUSIONS: Individualized whole course nutrition management had the potential to maintain nutritional status and decrease the adverse effects of radiotherapy in NPCs.

Block-Random Copolymer-Micellization-Mediated Formation of Polymeric Patches on Gold Nanoparticles.

Patchy colloidal nanoparticles are important for a broad range of applications, especially as building blocks for complex and functional structural materials, but the controllable generation of chemical patches on as-synthesized nanoparticles remains a challenge. This article describes a robust strategy for the scalable synthesis of high-quality patchy nanoparticles in high yield and solid content. A simple thermal treatment of a mixture of gold nanoparticles and thiol-terminated block-random copolymers in selected solvents produced a variety of patchy nanoparticles with a controlled morphology and number of polymeric patches (e.g., beanlike patch, one patch, two patches, three patches, multiple patches, and open-configuration patch). We show in experiments and simulations that the dynamic detachment/attachment of copolymers and the exchange of copolymers between the nanoparticle surface and free micelles in the solution-which are dictated by the architecture of copolymers-govern the formation of polymeric patches. This work not only offers an effective approach to patchy nanoparticles but also provides new insights into the phase behaviors of copolymers on nanoscale surfaces.

Polymer-guided assembly of inorganic nanoparticles.

The self-assembly of inorganic nanoparticles is of great importance in realizing their enormous potentials for broad applications due to the advanced collective properties of nanoparticle ensembles. Various molecular ligands (e.g., small molecules, DNAs, proteins, and polymers) have been used to assist the organization of inorganic nanoparticles into functional structures at different hierarchical levels. Among others, polymers are particularly attractive for use in nanoparticle assembly, because of the complex architectures and rich functionalities of assembled structures enabled by polymers. Polymer-guided assembly of nanoparticles has emerged as a powerful route to fabricate functional materials with desired mechanical, optical, electronic or magnetic properties for a broad range of applications such as sensing, nanomedicine, catalysis, energy storage/conversion, data storage, electronics and photonics. In this review article, we summarize recent advances in the polymer-guided self-assembly of inorganic nanoparticles in both bulk thin films and solution, with an emphasis on the role of polymers in the assembly process and functions of resulting nanostructures. Precise control over the location/arrangement, interparticle interaction, and packing of inorganic nanoparticles at various scales are highlighted.

Parenting Practices, Family Obligation, and Adolescents' Academic Adjustment: Cohort Differences with Social Change in China.

This study examined possible changes in the functions of parenting practices across different historical time points in terms of the effects of parenting practices on adolescents' academic adjustment and their indirect effects via family obligation values. This study used a time-lagged design that recruited Chinese high school students in 2010 (N = 1,040) and 2018 (N = 1,302). Structured equation modeling revealed the total effects of acceptance/involvement and strictness/supervision on academic adjustment and their indirect effects through family obligation values were positive and statistically equivalent across cohorts. However, the indirect effect of psychological autonomy granting on academic adjustment through family obligation values was negative in 2010 (in rural) but was not statistically significant in 2018 (urban and rural). These findings indicate that along with the sociodemographic change toward Gesellschaft (e.g., more urbanized, wealthier, higher level of education), psychological autonomy granting tends to exert less negative influence on adolescents' adjustment in the later cohort.

Developmental changes in associations between depressive symptoms and peer relationships: a four-year follow-up of Chinese adolescents.

Interpersonal theories have suggested that depressive symptoms influence and are influenced by peer relationships, but little is known about how depressive symptoms-peer relationships associations change with age. This study examined the longitudinal associations between both group- and dyadic-level peer relationships and depressive symptoms in a community sample of Chinese youth (n = 2179; 47.9% girls) from grades 6 to 9. Results demonstrated correlations between stable trait-like components of peer acceptance/rejection and depressive symptoms, with no dynamic state-like associations being observed. The results also suggested that conflict with friends operated as a consistent interpersonal risk for subsequent depressive symptoms across late childhood to middle adolescence. Support from friends was not significantly associated with depressive symptoms in early adolescence, but influenced and was influenced by depressive symptoms in middle adolescence. This study highlights that depressive symptoms are associated with youth's peer social status and friendship in different ways and that the interactions between friendship and depressive symptoms get strengthened with the transition to adolescence.

Alternating Copolymerization of Inorganic Nanoparticles.

Nanoparticle self-assembly has emerged as an indispensable tool in designing structured materials with a wide range of applications, but quantitatively predicting the assembly process and structures still remains challenging. Drawing inspiration from the toolbox of molecular reactions and behaviors is of utmost importance in further advancement of principles and theories for assembling nanoparticles at a length scale orders of magnitude larger. Here we represent a general paradigm for the predictive self-assembly of binary inorganic nanoparticles into linear nanostructures in periodic sequence by expanding the horizon of alternating copolymerization at the molecular level to nanoscale colloidal systems. Nanoparticles grafted with reactive block copolymers are viewed as nanoscale monomers ("nanomers"), and the rapid dimerization of co-nanomers into molecular dipole-like dimers, resembling the preferential formation of dimeric intermediates or charge-transfer complexes from co-monomers in molecular copolymerization, is crucial to the organization of co-nanomers in alternating sequence. We also demonstrate that the classic kinetics and statistics of polycondensation of molecular alternating copolymers (e.g., Nylon-66) can be utilized to quantitatively predict the copolymerization process of nanomers.

Effect of the LHCII pigment-protein complex aggregation on photovoltaic properties of sensitized TiO2 solar cells.

A modified dye-sensitized solar cell consisting of a thin TiO2 barrier layer sensitized with natural trimeric light-harvesting complex II (LHCII) from spinach was used as a biomimetic model to study the effects of LHCII aggregation on the photovoltaic properties. The aggregation of individual trimers induced molecular reorganization, which dramatically increased the photocurrent. The morphology of small- and large-size LHCII aggregates deposited on a surface was confirmed by atomic force microscopy. Enhanced LHCII immobilization was accomplished via electrostatic interaction with amine-functionalized photoanodes. The photocurrent responses of the assembled solar cells under illumination at three characteristic wavelength bands in the UV-Vis absorption spectra of LHCII solutions confirmed that a significant photocurrent was generated by LHCII photosensitizers. The enhanced photocurrent by large aggregated LHCII is shown to correlate with the quenching in the far-red fluorescence deriving from chlorophyll-chlorophyll charge transfer states that are effectively coupled with the TiO2 surface and thus inject electrons into the TiO2 conduction band. The large aggregated LHCII with more chlorophyll-chlorophyll charge transfer states is a much better sensitizer since it injects electrons more efficiently into the conduction band of TiO2 than the small aggregated LHCII mostly consisting of unquenched chlorophyll excited state. The assembled solar cells demonstrated remarkable stability in both aqueous buffer and acetonitrile electrolytes over 30 days.

Long non-coding RNA MIAT serves as a biomarker of fragility fracture and promotes fracture healing.

BACKGROUND: Fragility fracture is common in the elderly. Osteoblast differentiation is essential for bone healing and regeneration. Expression pattern of long non-coding RNA MIAT during fracture healing was examined, and its role in osteoblast differentiation was investigated. METHODS: 90 women with simple osteoporosis and 90 women with fragility fractures were included. Another 90 age-matched women were set as the control group. mRNA levels were tested using RT-qPCR. Cell viability was detected via CCK-8, and osteoblastic biomarkers, including ALP, OCN, Collagen I, and RUNX2 were tested via ELISA. The downstream miRNAs and genes targeted by MIAT were predicted by bioinformatics analysis, whose functions and pathways were annotated via GO and KEGG analysis. RESULTS: Serum MIAT was upregulated in osteoporosis women with high accuracy of diagnostic efficacy. Serum MIAT was even elevated in the fragility fracture group, but decreased in a time manner after operation. MIAT knockdown promoted osteogenic proliferation and differentiation of MC3T3-E1, but the influences were reversed by miR-181a-5p inhibitor. A total of 137 overlapping target genes of miR-181a-5p were predicted based on the miRDB, TargetScan and microT datasets, which were mainly enriched for terms related to signaling pathways regulating pluripotency of stem cells, cellular senescence, and osteoclast differentiation. CONCLUSIONS: LncRNA MIAT serves as a promising biomarker for osteoporosis, and promotes osteogenic differentiation via targeting miR-181a-5p.

Accelerated biological aging as a potential risk factor for rheumatoid arthritis.

OBJECTS: Previous studies have suggested a potential correlation between rheumatoid arthritis (RA) and biological aging, but the intricate connections and mechanisms remain elusive. METHODS: In our study, we focused on two specific measures of biological age (PhenoAge and BioAge), which are derived from clinical biomarkers. The residuals of these measures, when compared to chronological age, are defined as biological age accelerations (BAAs). Utilizing the extensive UK Biobank dataset along with various genetic datasets, we conducted a thorough assessment of the relationship between BAAs and RA at both the individual and aggregate levels. RESULTS: Our observational studies revealed positive correlations between the two BAAs and the risk of developing both RA and seropositive RA. Furthermore, the genetic risk score (GRS) for PhenoAgeAccel was associated with an increased risk of RA and seropositive RA. Linkage disequilibrium score regression (LDSC) analysis further supported these findings, revealing a positive genetic correlation between PhenoAgeAccel and RA. PLACO analysis identified 38 lead pleiotropic single nucleotide polymorphisms linked to 301 genes, providing valuable insights into the potential mechanisms connecting PhenoAgeAccel and RA. CONCLUSION: In summary, our study has successfully revealed a positive correlation between accelerated biological aging, as measured by BAAs, and the susceptibility to RA.

Genetic effects and causal association analyses of 14 common conditions/diseases in multimorbidity patterns.

BACKGROUND: Multimorbidity has become an important health challenge in the aging population. Accumulated evidence has shown that multimorbidity has complex association patterns, but the further mechanisms underlying the association patterns are largely unknown. METHODS: Summary statistics of 14 conditions/diseases were available from the genome-wide association study (GWAS). Linkage disequilibrium score regression analysis (LDSC) was applied to estimate the genetic correlations. Pleiotropic SNPs between two genetically correlated traits were detected using pleiotropic analysis under the composite null hypothesis (PLACO). PLACO-identified SNPs were mapped to genes by Functional Mapping and Annotation of Genome-Wide Association Studies (FUMA), and gene set enrichment analysis and tissue differential expression were performed for the pleiotropic genes. Two-sample Mendelian randomization analyses assessed the bidirectional causality between conditions/diseases. RESULTS: LDSC analyses revealed the genetic correlations for 20 pairs based on different two-disease combinations of 14 conditions/diseases, and genetic correlations for 10 pairs were significant after Bonferroni adjustment (P<0.05/91 = 5.49E-04). Significant pleiotropic SNPs were detected for 11 pairs of correlated conditions/diseases. The corresponding pleiotropic genes were differentially expressed in the brain, nerves, heart, and blood vessels and enriched in gluconeogenesis and drug metabolism, biotransformation, and neurons. Comprehensive causal analyses showed strong causality between hypertension, stroke, and high cholesterol, which drive the development of multiple diseases. CONCLUSIONS: This study highlighted the complex mechanisms underlying the association patterns that include the shared genetic components and causal effects among the 14 conditions/diseases. These findings have important implications for guiding the early diagnosis, management, and treatment of comorbidities.

Muscle-origin creatinine-cystatin C ratio is an osteoporosis marker in individuals with normal renal function: evidence from observational and Mendelian randomization analysis.

Background: Creatinine-cystatin C ratio (CCR) has been demonstrated as an objective marker of sarcopenia in clinical conditions but has not been evaluated as an osteoporosis marker in individuals with normal renal function. Methods: We selected 271,831 participants with normal renal function from UK Biobank cohort. Multivariable linear/logistic regression and Cox proportional hazards model were used to investigate the phenotypic relationship between CCR and osteoporosis in total subjects and gender-stratified subjects. Based on the genome-wide association study (GWAS) data, linkage disequilibrium regression (LDSC) and Mendelian randomization (MR) analysis were performed to reveal the shared genetic correlations and infer the causal effects, respectively. Results: Amongst total subjects and gender-stratified subjects, serum CCR was positively associated with eBMD after adjusting for potential risk factors (all P<0.05). The multivariable logistic regression model showed that the decrease in CCR was associated with a higher risk of osteoporosis/fracture in all models (all P<0.05). In the multivariable Cox regression analysis with adjustment for potential confounders, reduced CCR is associated with the incidence of osteoporosis and fracture in both total subjects and gender-stratified subjects (all P<0.05). A significant non-linear dose-response was observed between CCR and osteoporosis/fracture risk (P non-linearity < 0.05). LDSC found no significant shared genetic effects by them, but PLACO identified 42 pleiotropic SNPs shared by CCR and fracture (P<5×10-8). MR analyses indicated the causal effect from CCR to osteoporosis/fracture. Conclusions: Reduced CCR predicted increased risks of osteoporosis/fracture, and significant causal effects support their associations. These findings indicated that the muscle-origin serum CCR was a potential biomarker to assess the risks of osteoporosis and fracture.

Peiminine ameliorates Crohn's disease-like colitis by enhancing the function of the intestinal epithelial barrier through Nrf2/HO1 signal.

BACKGROUND AND AIMS: Impaired intestinal barrier function is key in maintaining intestinal inflammation in Crohn's disease (CD). However, no targeted treatment in clinical practice has been developed. Peiminine (Pm) strongly protects the epithelial barrier, the purpose of this study is to investigate whether Pm affects CD-like colitis and potential mechanisms for its action. METHODS: Trinitro-benzene-sulfonic acid (TNBS)-induced mice and Il-10-/- mice were used as CD animal models. Colitis symptoms, histological analysis, and intestinal barrier permeability were used to assess the Pm's therapeutic effect on CD-like colitis. The colon organoids were induced by TNF-α to evaluate the direct role of Pm in inhibiting apoptosis of the intestinal epithelial cells. Western blotting and small molecule inhibitors were used to investigate further the potential mechanism of Pm in inhibiting apoptosis of intestinal epithelial cells. RESULTS: Pm treatment reduced body weight loss, disease activity index (DAI) score, and inflammatory score, demonstrating that colonic inflammation in mice were alleviated. Pm decreased the intestinal epithelial apoptosis, improved the intestinal barrier function, and prevented the loss of tight junction proteins (ZO1 and claudin-1) in the colon of CD mice and TNF-α-induced colonic organoids. Pm activated Nrf2/HO1 signaling, which may protect intestinal barrier function. CONCLUSIONS: Pm inhibits intestinal epithelial apoptosis in CD mice by activating Nrf2/HO1 pathway. This partially explains the potential mechanism of Pm in ameliorating intestinal barrier function in mice and provides a new approach to treating CD.

Pathological discrimination between luteinized thecoma associated with sclerosing peritonitis and thecoma.

BACKGROUND: Similarities between luteinized thecoma associated with sclerosing peritonitis (LTSP) and thecoma, cause difficulty in clinical differential diagnoses. To improve the situation, we selected 10 specified molecular pathological markers that are frequently used in clinical pathology of ovarian sex cord-stromal tumors to determine whether they exert a discriminatory effect. METHODS: Applying immunohistochemistry, we analyzed the expression of alpha-1,6-mannosylglycoprotein 6-beta-n-acetylglucosaminyltransferase B (MGAT5B), nuclear receptor coactivator 3 (NCOA3), proliferation marker protein Ki-67 (MKI67), estrogen receptor, progesterone receptor, Vimentin, receptor tyrosine-protein kinase erbB-2, Catenin beta-1 (ß-Catenin), CD99 antigen (CD99) and Wilms tumor protein (WT1) in 102 cases of diseases containing 11 LTSP and 91 thecoma. Whole-exome sequencing and fluorescence in situ hybridization were used to examine the MGAT5B-NCOA3 fusion gene in LTSP. Statistical analysis was performed using t test, one-way analysis of variance test, and post hoc test. RESULTS: Six significant markers were verified for the discrimination between LTSP and thecoma, containing 4 upregulating indicators MGAT5B, NCOA3, MKI67, ß-Catenin, and 2 downregulating markers CD99 and WT1 in luteinized cells. In addition, the MGAT5B-NCOA3 fusion gene was identified in LTSP for the first time with significantly rich expression compared to thecoma. CONCLUSIONS: We verified 6 significant molecular pathological markers containing MGAT5B, NCOA3, MKI67, ß-Catenin, CD99, and WT1 and identified MGAT5B-NCOA3 fusion gene in LTSP; this work will help clinicians to discriminate between medical conditions and treat patients accurately.