Biosynthesis and Assembly Logic of Fungal Hybrid Terpenoid Natural Products.

In recent decades, fungi have emerged as significant sources of diverse hybrid terpenoid natural products, and their biosynthetic pathways are increasingly unveiled. This review mainly focuses on elucidating the various strategies underlying the biosynthesis and assembly logic of these compounds. These pathways combine terpenoid moieties with diverse building blocks including polyketides, nonribosomal peptides, amino acids, p-hydroxybenzoic acid, saccharides, and adenine, resulting in the formation of plenty of hybrid terpenoid natural products via C-O, C-C, or C-N bond linkages. Subsequent tailoring steps, such as oxidation, cyclization, and rearrangement, further enhance the biological diversity and structural complexity of these hybrid terpenoid natural products. Understanding these biosynthetic mechanisms holds promise for the discovery of novel hybrid terpenoid natural products from fungi, which will promote the development of potential drug candidates in the future.

Comprehensive analysis revealed the immunoinflammatory targets of rheumatoid arthritis based on intestinal flora, miRNA, transcription factors, and RNA-binding proteins databases, GSEA and GSVA pathway observations, and immunoinfiltration typing.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory arthritis. This study aimed to identify potential biomarkers and possible pathogenesis of RA using various bioinformatics analysis tools. METHODS: The GMrepo database provided a visual representation of the analysis of intestinal flora. We selected the GSE55235 and GSE55457 datasets from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) separately. With the intersection of these DEGs with the target genes associated with RA found in the GeneCards database, we obtained the DEGs targeted by RA (DERATGs). Subsequently, Disease Ontology, Gene Ontology, and the Kyoto Encyclopedia of Genes and Genomes were used to analyze DERATGs functionally. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were performed on the data from the gene expression matrix. Additionally, the protein-protein interaction network, transcription factor (TF)-targets, target-drug, microRNA (miRNA)-mRNA networks, and RNA-binding proteins (RBPs)-DERATGs correlation analyses were built. The CIBERSORT was used to evaluate the inflammatory immune state. The single-sample GSEA (ssGSEA) algorithm and differential analysis of DERATGs were used among the infiltration degree subtypes. RESULTS: There were some correlations between the abundance of gut flora and the prevalence of RA. A total of 54 DERATGs were identified, mainly related to immune and inflammatory responses and immunodeficiency diseases. Through GSEA and GSVA analysis, we found pathway alterations related to metabolic regulations, autoimmune diseases, and immunodeficiency-related disorders. We obtained 20 hub genes and 2 subnetworks. Additionally, we found that 39 TFs, 174 drugs, 2310 miRNAs, and several RBPs were related to DERATGs. Mast, plasma, and naive B cells differed during immune infiltration. We discovered DERATGs' differences among subtypes using the ssGSEA algorithm and subtype grouping. CONCLUSIONS: The findings of this study could help with RA diagnosis, prognosis, and targeted molecular treatment.

An automated ICU agitation monitoring system for video streaming using deep learning classification.

OBJECTIVE: To address the challenge of assessing sedation status in critically ill patients in the intensive care unit (ICU), we aimed to develop a non-contact automatic classifier of agitation using artificial intelligence and deep learning. METHODS: We collected the video recordings of ICU patients and cut them into 30-second (30-s) and 2-second (2-s) segments. All of the segments were annotated with the status of agitation as "Attention" and "Non-attention". After transforming the video segments into movement quantification, we constructed the models of agitation classifiers with Threshold, Random Forest, and LSTM and evaluated their performances. RESULTS: The video recording segmentation yielded 427 30-s and 6405 2-s segments from 61 patients for model construction. The LSTM model achieved remarkable accuracy (ACC 0.92, AUC 0.91), outperforming other methods. CONCLUSION: Our study proposes an advanced monitoring system combining LSTM and image processing to ensure mild patient sedation in ICU care. LSTM proves to be the optimal choice for accurate monitoring. Future efforts should prioritize expanding data collection and enhancing system integration for practical application.

Rapamycin can alleviate the submandibular gland pathology of Sjögren's syndrome by limiting the activation of cGAS-STING signaling pathway.

BACKGROUND: Sjögren's Syndrome (SS) is also known as autoimmune exocrine gland disease. Previous studies have confirmed that adaptive immunity plays an important role in the development of this disease. But less is known about the role of the innate immune system. METHODS: To identify the core pathways, and local infiltrated immune cells in the local immune microenvironment of SS. We verified the activation of these core genes and core signaling pathways in SS model mice by in vivo experiment and transcriptome sequencing. RESULTS: Finally, we identified 6 core genes EPSTI1, IFI44L, MX1, CXCL10, IFIT3, and IFI44. All the 6 genes had good diagnostic value. Based on multi-omics sequencing results and experimental studies, we found that cGAS-STING signaling pathway is most relevant to the pathogenesis of SS. By in vivo experiments, we verified that autophagy is the key brake to limit the activation of cGAS-STING signaling pathway. CONCLUSIONS: Maladaptive activation of autophagy and cGAS-STING signaling pathway are central contributors to the SG pathogenesis of pSS patient. Regulating autophagy by rapamycin may be a possible treatment for Sjögren's syndrome in the future.

Dynamic biomechanical changes of clear aligners during extraction space closure: Finite element analysis.

INTRODUCTION: Clear aligners (CAs) have recently become popular and widely used orthodontic appliances. Research on CA biomechanics has become a focal point in orthodontics to improve the efficiency of CA treatment and address challenging issues, such as extraction. The biomechanical characteristics of CAs in space closure have been reported. However, previous studies have mainly focused on static biomechanical analysis that cannot demonstrate the dynamic biomechanical changes in CAs during space-closing. Given that these biomechanical changes can be significant and have considerable clinical value, this study aimed to investigate these characteristics. METHODS: Sequential extraction space-closing models were derived from included patient data and refined using modeling and CA design software. A finite element analysis was performed to obtain biomechanical raw data. This study introduced a dual coordinate system and space geometry analysis to demonstrate the biomechanical properties accurately. RESULTS: As space closure progressed, the instantaneous tooth displacements increased, indicating an enhanced space closure force because of the increased strain in the CA extraction area. Meanwhile, the central axis of rotation of the anterior teeth continuously moved toward the labial-apical direction, showing a gradually enhanced vertical and torque control effect. CONCLUSIONS: During space closure, CAs undergo specific biomechanical changes, including increased contraction and control forces on both sides of the gap. These biomechanical effects are beneficial to alleviate the roller coaster effect gradually. Meanwhile, more reasonable staging design strategies can be proposed on the basis of this biomechanical mechanism.

Different biomechanical effects of clear aligners in closing maxillary and mandibular extraction spaces: Finite element analysis.

INTRODUCTION: Compared with fixed treatments, clear aligners (CAs) have the advantages of comfort, esthetics, and hygiene, and are popular among patients and orthodontists. However, CAs exhibit control deficiencies in extraction patients because of insufficient root control and retention effects. These deficiencies can magnify biomechanical differences in bimaxillary dentition, further causing different orthodontic requirements between maxillary and mandibular dentition. This study aimed to elaborate on the biomechanical characteristics of bimaxillary dentition in extraction space closure and provided feasible biomechanical compensation strategies for use in clinical practice. METHODS: We constructed a 3-dimensional (3D) bimaxillary model based on patient data. Several 3D modeling-related software was used to generate a standard first premolar extraction model, CAs, and attachments. Subsequently, finite element analysis was performed to demonstrate the biomechanical effects. RESULTS: The maxillary and mandibular dentition showed a roller coaster effect during space closure. Compared with the maxillary dentition, the mandibular posterior teeth exhibited stronger relative anchorage causing greater anterior teeth retraction. The tipping and vertical movements of the anterior teeth were related to tooth length. The longer the anterior tooth, the less tipping and greater vertical displacement occurred. Generally, when having the same retraction distance, the mandibular dentition exhibited greater retroclination and fewer extrusions. Both mechanical and retention compensations should be considered to prevent these unwanted tipping movements. Adding specific attachments to bimaxillary dentitions compensated for the retention and root control deficiencies of CAs. CONCLUSIONS: When applying CAs to extraction patients, different biomechanical effects can present in the bimaxillary dentition because of specific dentition morphologies. To effectively treat these patients, mechanical compensation through overcorrection of the target position should be designed on the basis of bimaxillary control deficiencies, and retention compensation by adding specific attachments should also be considered according to the overcorrections.

Finite element analysis of the biomechanical effect of clear aligners in extraction space closure under different anchorage controls.

INTRODUCTION: Clear aligners (CAs) have attracted increasing attention from patients and orthodontists because of their excellent esthetics and comfort. However, treating tooth extraction patients with CAs is difficult because their biomechanical effects are more complicated than those of traditional appliances. This study aimed to analyze the biomechanical effect of CAs in extraction space closure under different anchorage controls, including moderate, direct strong, and indirect strong anchorage. It could provide several new cognitions for anchorage control with CAs through finite element analysis, further directing clinical practice. METHODS: A 3-dimensional maxillary model was generated by combining cone-beam computed tomography and intraoral scan data. Three-dimensional modeling software was used to construct a standard first premolar extraction model, temporary anchorage devices, and CAs. Subsequently, finite element analysis was performed to simulate space closure under different anchorage controls. RESULTS: Direct strong anchorage was beneficial for reducing the clockwise occlusal plane rotation, whereas indirect anchorage was conducive for anterior teeth inclination control. In the direct strong anchorage group, an increase in the retraction force would require more specific anterior teeth overcorrection to resist the tipping movement, mainly including lingual root control of the central incisor, followed by distal root control of the canine, lingual root control of the lateral incisor, distal root control of the lateral incisor, and distal root control of the central incisor. However, the retraction force could not eliminate the mesial movement of the posterior teeth, possibly causing a reciprocating motion during treatment. In indirect strong groups, when the button was close to the center of the crown, the second premolar presented less mesial and buccal tipping but more intrusion. CONCLUSIONS: The 3 anchorage groups showed significantly different biomechanical effects in both the anterior and posterior teeth. Specific overcorrection or compensation forces should be considered when using different anchorage types. The moderate and indirect strong anchorages have a more stable and single-force system and could be reliable models in investigating the precise control of future tooth extraction patients.

Biosynthesis of Cosmosporasides Reveals the Assembly Line for Fungal Hybrid Terpenoid Saccharides.

Fungal hybrid terpenoid saccharides constitute a new and growing family of natural products with significant biomedical and agricultural activities. One representative family is the cosmosporasides, which feature oxidized terpenoid units and saccharide moieties; however, the assembly line of these building blocks has been elusive. Herein, a cos cluster from Fusarium orthoceras was discovered for the synthesis of cosmosporaside C (1) by genome mining. A UbiA family intramembrane prenyltransferase (UbiA-type PT), a multifunctional cytochrome P450, an α,ß-hydrolase, an acetyltransferase, a dimethylallyl transferase (DMAT-type PT) and a glycosyltransferase function cooperatively in the assembly of the scaffold of 1 using primary central metabolites. The absolute configuration at C4, C6 and C7 of 1 was also established. Our work clarifies the unexpected functions of UbiA-type and DMAT-type PTs and provides an example for understanding the synthetic logic of hybrid terpenoid saccharides in fungi.

Topographic Cues Guiding Cell Polarization via Distinct Cellular Mechanosensing Pathways.

Cell polarization exists in a variety of tissues to regulate cell behaviors and functions. Space constraint (spatially limiting cell extension) and adhesion induction (guiding adhesome growth) are two main ways to induce cell polarization according to the microenvironment topographies. However, the mechanism of cell polarization induced by these two ways and the downstream effects on cell functions are yet to be understood. Here, space constraint and adhesion induction guiding cell polarization are achieved by substrate groove arrays in micro and nano size, respectively. Although the morphology of polarized cells is similar on both structures, the signaling pathways to induce the cell polarization and the downstream functions are distinctly different. The adhesion induction (nano-groove) leads to the formation of focal adhesions and activates the RhoA/ROCK pathway to enhance the myosin-based intracellular force, while the space constraint (micro-groove) only activates the formation of pseudopodia. The enhanced intracellular force caused by adhesion induction inhibits the chromatin condensation, which promotes the osteogenic differentiation of stem cells. This study presents an overview of cell polarization and mechanosensing at biointerface to aid in the design of novel biomaterials.

Microchemical Engineering in a 3D Ordered Channel Enhances Electrocatalysis.

The kinetics of electrode reactions including mass transfer and surface reaction is essential in electrocatalysis, as it strongly determines the apparent reaction rates, especially on nanostructured electrocatalysts. However, important challenges still remain in optimizing the kinetics of given catalysts with suitable constituents, morphology, and crystalline design to maximize the electrocatalytic performances. We propose a comprehensive kinetic model coupling mass transfer and surface reaction on the nanocatalyst-modified electrode surface to explore and shed light on the kinetic optimization in electrocatalysis. Moreover, a theory-guided microchemical engineering (MCE) strategy has been demonstrated to rationally redesign the catalysts with optimized kinetics. Experimental measurements for methanol oxidation reaction in a 3D ordered channel with tunable channel sizes confirm the calculation prediction. Under the optimized channel size, mass transfer and surface reaction in the channeled microreactor are both well regulated. This MCE strategy will bring about a significant leap forward in structured catalyst design and kinetic modulation.

Critical roles of cytokine storm and secondary bacterial infection in acute kidney injury development in COVID-19: A multi-center retrospective cohort study.

Acute kidney injury (AKI) may develop in patients with coronavirus disease 2019 (COVID-19) and is associated with in-hospital death. We investigated the incidence of AKI in 223 hospitalized COVID-19 patients and analyzed the influence factors of AKI. The incidence of cytokine storm syndrome and its correlation with other clinicopathologic variables were also investigated. We retrospectively enrolled adult patients with virologically confirmed COVID-19 who were hospitalized at three hospitals in Wuhan and Guizhou, China between February 13, 2020, and April 8, 2020. We included 124 patients with moderate COVID-19 and 99 with severe COVID-19. AKI was present in 35 (15.7%) patients. The incidence of AKI was 30.3% for severe COVID-19 and 4.0% for moderate COVID-19 (p < 0.001). Furthermore, cytokine storm was found in 30 (13.5%) patients and only found in the severe group. Kidney injury at admission (odds ratio [OR]: 3.132, 95% confidence interval [CI]: 1.150-8.527; p = 0.025), cytokine storm (OR: 4.234, 95% CI: 1.361-13.171; p = 0.013), and acute respiratory distress syndrome (ARDS) (OR: 7.684, 95% CI: 2.622-22.523; p < 0.001) were influence factors of AKI. Seventeen (48.6%) patients who received invasive mechanical ventilation developed AKI, of whom 64.7% (11/17) died. Up to 86.7% of AKI patients with cytokine storms may develop a secondary bacterial infection. The leukocyte counts were significantly higher in AKI patients with cytokine storm than in those without (13.0 × 109/L, interquartile range [IQR] 11.3 vs. 8.3 × 109/L, IQR 7.5, p = 0.005). Approximately 1/6 patients with COVID-19 eventually develop AKI. Kidney injury at admission, cytokine storm and ARDS are influence factors of AKI. Cytokine storm and secondary bacterial infections may be responsible for AKI development in COVID-19 patients.

Platinum-based chemotherapy in advanced triple-negative breast cancer: A multicenter real-world study in China.

Platinum-based chemotherapy (PBC) has proven benefits in phase III studies for advanced triple-negative breast cancer (TNBC) patients; however, real-world data of large samples from multiple centers are lacking. Our study was to compare the effectiveness of PBC and non-PBC in advanced TNBC patients in multicenter real-world settings. Totally, 495 patients with advanced TNBC receiving PBC (n = 350) or non-PBC (n = 145) at four cancer centers in China between 2003 and 2019 were included. Treatment responses and outcomes were compared between the two groups from first-line to third-line treatment. Of patients with PBC, 249 (71.1%) received PBC from first-line chemotherapy, 86 (24.6%) from second-line and 15 (4.3%) from third-line treatment. In first-line treatment, PBC was superior to non-PBC in objective response rate (ORR, 53.0% vs 32.1%, P < .001) and median progression-free survival (PFS, 8.4 vs 6.0 months, P = .022), whereas overall survival (OS) was similar (19.2 vs 16.8 months, P = .439). When comparing patients receiving non-PBC doublets (n = 221) with those receiving PBC doublets (n = 249), the same trend was observed in ORR (32.6% vs 53.0%, P < .001), median first-line PFS (6.5 vs 8.4 months, P = .041) and median first-line OS(17.8 vs 19.2 months, P = .568). Paclitaxel/docetaxel + platinum was more likely to be used, followed by gemcitabine + platinum. In second/third-line treatment, PBC yielded a similar response and survival compared to non-PBC. Adding PBC in the first-line therapy was better than that in the latter-line of treatment in terms of ORR, PFS and OS (P < .001). Toxic effects of PBC were tolerable and the most common adverse event was neutropenia (38.6%). PBC doublets exhibited superior efficacy and manageable toxicity compared to non-PBC doublets in the first-line treatment for Chinese mTNBC patients.

Association of CD14 gene -260C>T and -561C>T polymorphisms with cancer susceptibility: A meta-analysis.

BACKGROUND: Two polymorphisms, -260C>T (rs2569190) and -561C>T (rs5744455), in the CD14 gene have been implicated in susceptibility to cancer. However, the results remain inconclusive. The current meta-analysis was carried out aiming to confirm the function of these two polymorphisms on the susceptibility of cancer. METHODS: We collected eligible studies from databases, including PubMed, EMBASE, CNKI, Wanfang, and VIP (Weipu). We used logistic regression calculation to compute odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: After strict selection, 24 studies with 5854 cases and 10339 controls for -260C>T and seven studies with 1809 cases and 7289 controls for -561C>T were finally enlisted into our analysis reference material. Pool results revealed that neither -260C>T, nor -561C>T was found to have any association with overall cancer susceptibility. Nevertheless, when stratified by cancer type, we detected a decreased risk associated with other cancers in a heterozygous model (OR = 0.69, 95% CI = 0.51-0.93, p = 0.014) and a dominant model (OR = 0.70, 95% CI = 0.53-0.93, p = 0.012) for -561C>T. An increased risk was found in other cancers under an allele model (OR = 1.29, 95% CI = 1.03-1.62, p = 0.026), in laryngeal cancer under a dominant model (OR = 1.38, 95% CI = 1.11-1.71, p = 0.003) and for a score ≤ 9 under a recessive model (OR = 1.45, 95% CI = 1.09-1.91, p = 0.009) for -561C>T. CONCLUSIONS: In the present study, we conclude that the CD14 -260C>T and -561C>T polymorphisms might not be associated with overall cancer risk. Further studies are encouraged to confirm this conclusion.

Stripped Electrode Based Electrowetting-on-Dielectric Digital Microfluidics for Precise and Controllable Parallel Microdrop Generation.

Microdrop generation with excellent controllability and volume precision is of paramount significance for a large variety of microfluidic applications. In this work, we propose a new configuration comprising only stripped electrodes of rectangular shape for the closed electrowetting-on-dielectric digital microfluidic (EWOD DMF) system and investigate its parallel microdrop generation outcomes via a numerical approach. The microfluidic droplet motion is solved by a finite-volume scheme on a fixed computational domain. The numerical model is verified by an experimental study of microdrop production from an EWOD DMF device with three different electrode designs. After model verification, we examine the influences of the equilibrium contact angle and the spacing of the microchannel on stripped electrode based microdrop generation outcomes and discover five different regimes including the phenomena of satellite droplet formation and separation cessation. Despite the various generation outcomes, the daughter droplet size is found to vary linearly with a dimensionless EWOD parameter κ*. More importantly, for all successful generations, the deviation of the daughter droplet size from that of the stripped electrode is smaller than 3.5%, which even reaches zero in proper conditions. This new configuration can be utilized as a convenient alternative for electrowetting-induced parallel microdrop production with excellent precision and controllability.

A selective and robust UPLC-MS/MS method for the simultaneous quantitative determination of anlotinib, ceritinib and ibrutinib in rat plasma and its application to a pharmacokinetic study.

A selective and robust UPLC-MS/MS method has been firstly developed for simultaneous determination of three anti-tumor tyrosine kinase inhibitors (anlotinib, ANL; ceritinib, CER; ibrutinib, IBR) in rat plasma using cost-effective protein precipitation extraction. LC separation was achieved on Waters XBrige C18 column (50 mm × 2.1 mm, 3.5 µm) under gradient conditions in a run time of 5 min. ESI+ was involved through mass spectrometry. Multiple reaction monitoring transitions were at m/z 408.2 → 339.2 for ANL, 558.2 → 433.2 for CER, 441.0 → 138.0 for IBR, 285.0 → 193.1 for diazepam (internal standard), respectively. The optimized method was validated based on US FDA guideline, EMEA guideline as well as Pharmacopoeia of the People's Republic of China. The assay was linear in the range of 0.1-20 ng mL-1 for ANL, 2-1000 ng mL-1 for CER, 1-500 ng mL-1 for IBR. Intra- and inter-day accuracy and precision for all analytes were ≦13.84% and ≦12.56%, respectively. ANL, CER and IBR were sufficiently stable under most investigated conditions. The optimized method was successfully applied for a pharmacokinetic study after single oral gavage administration of mixture (ANL, CER and IBR) at dose of 6 mg kg-1, 25 mg kg-1 and 10 mg kg-1.

The UV absorption of graphene oxide is size-dependent: possible calibration pitfalls.

Graphene oxide (GO) is often quantified via its UV absorption, typically at around 230 nm. This is convenient but the effect of the size of GO on the accuracy of this method has been ignored so far. The authors report that the molar absorbance of GO is size-dependent. Data are presented on the absorbance of small (hydrodynamic diameter 1 µm), medium sized (1.5 µm), and large (2.2 µm) GO particles at wavelengths of 210, 230 and 250 nm. In general, linear relationship and good regression fits are obtained, but with different slope depending on size even at the same wavelength. This implies that using the UV absorption-based calibration may cause significant errors in GO quantification. Ultimately, this leads to incorrect dosages and faulty conclusions. This may also explain a variety of inconsistent results obtained in previous biological applications of GO. Graphical abstract The size of graphene oxide (GO) determines its UV absorption and the UV absorption-based calibration (GO-s, GO-m and GO-l represent the GO with small, medium and large size).

[The relationship between anti-phospholipase A2 receptor antibody and idiopathic membranous nephropathy].

OBJECTIVE: To explore the value of anti-phospholipase A2 receptor (PLA2R) antibody in the diagnosis and disease activity monitoring of idiopathic membranous nephropathy (IMN). METHODS: A total of 233 patients with IMN proven by kidney biopsy at Peking Union Medical College Hospital from January 2012 to March 2014 were enrolled in this study. Another 46 patients with non-IMN kidney diseases at the same period were selected as control group. Serum titer of anti-PLA2R antibody was measured by quantitative enzyme-linked immuno sorbent assay (ELISA) at the time of renal biopsy. Clinical data were reviewed and retrospectively analyzed. The diagnostic accuracy of anti-PLA2R antibody in IMN was estimated by ROC curve. RESULTS: The total sensitivity of anti-PLA2R antibody was 60.0% in IMN. However, the sensitivity increased to 71.3% in patients who did not receive immuno-suppression therapies. The specificity of anti-PLA2R antibody was 100.0%, of which was not detected in any of the 25 control patients with lupus nephritis. The area under ROC curve of anti-PLA2R antibody for IMN diagnosis was 0.800. The prevalence of positive anti-PLA2R antibody in nephrotic range proteinuria group and non-nephrotic range proteinuria group were 68.3% and 41.7% (P < 0.05), respectively. The positive rates in patients with serum albumin level less than 30 g/L and more than 30 g/L were 67.3% and 44.6% (P < 0.05), respectively. Hypoalbuminemia became worse (P < 0.05) and the proportion of nephrotic arrange proteinuria rose significantly (P < 0.05) according to the elevation of antibody level. CONCLUSIONS: Anti-PLA2R antibody has high sensitivity and notable specificity for the diagnosis of IMN, which reveals good diagnostic accuracy. The antibody positive rate is affected by immunosuppression therapy, disease activity and other clinical status. Moreover, the antibody could reflect the disease activity.

Dual intervention on the gut and skin microbiota attenuates facial cutaneous aging.

The gut and skin microbiota are microbial barriers, resisting harmful foreign microorganisms and maintaining internal homeostasis. Dysbiosis of the gut and skin microbiota is involved in aging progression. However, interventions targeting facial skin wellness taking into account the gut-skin axis are scarce. In this study, the impact of an eight-week intervention with oral (O), topical (T), and both oral and topical (OT) xylo-oligosaccharides (XOS) by regulating gut and skin microbiota on facial cutaneous aging was investigated in a double-blind placebo-controlled trial in females. An increase in the proportion of participants with skin rejuvenation was observed, along with a significant reduction in facial pores after OT intervention. The reduction of cutaneous Cutibacterium by OT intervention was greater than that in the O and T groups. These interventions can change the skin microbial structure. Intestinal Bifidobacterium was enriched only by dual treatment with oral and topical XOS. Function prediction analysis revealed a decrease in K02770 encoding fructose-1-phosphate kinase involved in de novo lipid synthesis from fructose with dual intervention, suggesting that inhibition of lipophilic Cutibacterium may contribute to reducing facial pores. Overall, the dual XOS intervention approach is most effective for improving both gut and skin microbiota, as well as facial skin aging.

Mucin-producing tumors of the ovary--preoperative differentiation between metastatic ovarian mucinous carcinoma and primary mucinous malignant tumors.

OBJECTIVE: To investigate the clinical and magnetic resonance imaging (MRI) features for preoperatively discriminating  primary ovarian mucinous malignant tumors (POMTs) and metastatic mucinous carcinomas involving the ovary (MOMCs). METHODS: This retrospective multicenter study enrolled 61 patients with 22 POMTs and 49 MOMCs, which were pathologically proved between November 2014 to Jane 2023. The clinical and MRI features were evaluated and compared between POMTs and MOMCs. Univariate and multivariate analyses were performed to identify the significant variables between the two groups, which were then incorporated into a predictive nomogram, and ROC curve analysis was subsequently carried out to evaluate diagnostic performance. RESULTS: 35.9% patients with MOMCs were discovered synchronously with the primary carcinomas; 25.6% patients with MOMCs were bilateral, and all of the patients with POMTs were unilateral. The biomarker CEA was significantly different between the two groups (p = 0.002). There were significant differences in the following MRI features: tumor size, configuration, enhanced pattern, the number of cysts, honeycomb sign, stained-glass appearance, ascites, size diversity ratio, signal diversity ratio. The locular size diversity ratio (p = 0.005, OR = 1.31), and signal intensity diversity ratio (p = 0.10, OR = 4.01) were independent predictors for MOMCs. The combination of above independent criteria yielded the largest area under curve of 0.922 with a sensitivity of 82.3% and specificity of 88.9%. CONCLUSIONS: Patients with MOMCs were more commonly bilaterally and having higher levels of CEA, but did not always had a malignant tumor history. For ovarian mucin-producing tumors, the uniform locular sizes and signal intensities were more predict MOMCs.

CXCL10 as a shared specific marker in rheumatoid arthritis and inflammatory bowel disease and a clue involved in the mechanism of intestinal flora in rheumatoid arthritis.

This study aimed to identify shared specific genes associated with rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) through bioinformatic analysis and to examine the role of the gut microbiome in RA. The data were extracted from the 3 RA and 1 IBD gene expression datasets and 1 RA gut microbiome metagenomic dataset. Weighted correlation network analysis (WGCNA) and machine learnings was performed to identify candidate genes associated with RA and IBD. Differential analysis and two different machine learning algorithms were used to investigate RA's gut microbiome characteristics. Subsequently, the shared specific genes related to the gut microbiome in RA were identified, and an interaction network was constructed utilizing the gutMGene, STITCH, and STRING databases. We identified 15 candidates shared genes through a joint analysis of the WGCNA for RA and IBD. The candidate gene CXCL10 was identified as the shared hub gene by the interaction network analysis of the corresponding WGCNA module gene to each disease, and CXCL10 was further identified as the shared specific gene by two machine learning algorithms. Additionally, we identified 3 RA-associated characteristic intestinal flora (Prevotella, Ruminococcus, and Ruminococcus bromii) and built a network of interactions between the microbiomes, genes, and pathways. Finally, it was discovered that the gene CXCL10 shared between IBD and RA was associated with the three gut microbiomes mentioned above. This study demonstrates the relationship between RA and IBD and provides a reference for research into the role of the gut microbiome in RA.