Potential mediation effect of insulin resistance on the association between iron metabolism indicators and non-alcoholic fatty liver disease.

OBJECTIVES: Iron metabolism and insulin resistance (IR) are closely related to non-alcoholic fatty liver disease (NAFLD). However, the interplay between them on the occurrence and progression of NAFLD is not fully understood. We aimed to disentangle the crosstalk between iron metabolism and IR and explore its impact on NAFLD. METHODS: We analyzed data from the National Health and Nutritional Examination Survey (NHANES) 2017-2018 to evaluate the association between serum iron metabolism indicators (ferritin, serum iron, unsaturated iron-binding capacity [UIBC], total iron-binding capacity [TIBC], transferrin saturation, and transferrin receptor) and NAFLD/non-alcoholic steatohepatitis (NASH). Mediation analysis was conducted to explore the role of IR played in these relationship. RESULTS: A total of 4812 participants were included, among whom 43.7% were diagnosed with NAFLD and 13.2% were further diagnosed with NASH. After adjusting the covariates, the risk of NAFLD increases with increasing serum ferritin (adjusted odds ratio [aOR] 1.71, 95% confidence interval [CI] 1.37-2.14), UIBC (aOR 1.45, 95% CI 1.17-1.79), and TIBC (aOR 1.36, 95% CI 1.11-1.68). Higher levels of serum ferritin (aOR 3.70, 95% CI 2.25-6.19) and TIBC (aOR 1.69, 95% CI 1.13-2.56) were also positively associated with NASH. Participants with IR were more likely to have NAFLD/NASH. Moreover, IR-mediated efficacy accounted for 85.85% and 64.51% between ferritin and NAFLD and NASH, respectively. CONCLUSION: Higher levels of serum ferritin and TIBC are closely associated with the occurrence of NAFLD and NASH. IR may be considered a possible link between NAFLD or NASH and increased serum ferritin levels.

Targeting epigenetic and post-translational modifications regulating pyroptosis for the treatment of inflammatory diseases.

Inflammatory diseases, including infectious diseases, diabetes-related diseases, arthritis-related diseases, neurological diseases, digestive diseases, and tumor, continue to threaten human health and impose a significant financial burden despite advancements in clinical treatment. Pyroptosis, a pro-inflammatory programmed cell death pathway, plays an important role in the regulation of inflammation. Moderate pyroptosis contributes to the activation of native immunity, whereas excessive pyroptosis is associated with the occurrence and progression of inflammation. Pyroptosis is complicated and tightly controlled by various factors. Accumulating evidence has confirmed that epigenetic modifications and post-translational modifications (PTMs) play vital roles in the regulation of pyroptosis. Epigenetic modifications, which include DNA methylation and histone modifications (such as methylation and acetylation), and post-translational modifications (such as ubiquitination, phosphorylation, and acetylation) precisely manipulate gene expression and protein functions at the transcriptional and post-translational levels, respectively. In this review, we summarize the major pathways of pyroptosis and focus on the regulatory roles and mechanisms of epigenetic and post-translational modifications of pyroptotic components. We also illustrate these within pyroptosis-associated inflammatory diseases. In addition, we discuss the effects of novel therapeutic strategies targeting epigenetic and post-translational modifications on pyroptosis, and provide prospective insight into the regulation of pyroptosis for the treatment of inflammatory diseases.

KCTD15 acts as an anti-tumor factor in colorectal cancer cells downstream of the demethylase FTO and the m6A reader YTHDF2.

Potassium Channel Tetramerization Domain Containing 15 (KCTD15) participates in the carcinogenesis of several solid malignancies; however, its role in colorectal cancer (CRC) remains unclear. Here we find that KCTD15 exhibits lower expression in CRC tissues as compared to para-carcinoma tissues. Tetracycline (tet)-induced overexpression and knockdown of KCTD15 confirms KCTD15 as an anti-proliferative and pro-apoptotic factor in CRC both in vitro and in xenografted tumors. N6-methyladenosine (m6A) is known to affect the expression, stabilization, and degradation of RNAs with this modification. We demonstrate that upregulation of fat mass and obesity-associated protein (FTO), a classical m6A eraser, prevents KCTD15 mRNA degradation in CRC cells. Less KCTD15 RNA is recognized by m6A 'reader' YTH N6-Methyladenosine RNA Binding Protein F2 (YTHDF2) in FTO-overexpressed cells. Moreover, KCTD15 overexpression decreases protein expression of histone deacetylase 1 (HDAC1) but increases acetylation of critical tumor suppressor p53 at Lys373 and Lys382. Degradation of p53 is delayed in CRC cells post-KCTD15 overexpression. We further show that the regulatory effects of KCTD15 on p53 are HDAC1-dependent. Collectively, we conclude that KCTD15 functions as an anti-growth factor in CRC cells, and its expression is orchestrated by the FTO-YTHDF2 axis. Enhanced p53 protein stabilization may contribute to KCTD15's actions in CRC cells.

Xiashengella succiniciproducens gen. nov., sp. nov., a succinate-producing bacterium isolated from an anaerobic digestion tank in the family Marinilabiliaceae of the order Bacteroidales.

A strictly anaerobic, motile bacterium, designated as strain Ai-910T, was isolated from the sludge of an anaerobic digestion tank in China. Cells were Gram-stain-negative rods. Optimal growth was observed at 38 °C (growth range 25-42 °C), pH 8.5 (growth range 5.5-10.5), and under a NaCl concentration of 0.06% (w/v) (range 0-2.0%). Major cellular fatty acids were iso-C15 : 0 and anteiso-C15 : 0. The respiratory quinone was MK-7. Using xylose as the growth substrate, succinate was produced as the fermentation product. Phylogenetic analysis based on the 16 S rRNA gene sequences indicated that strain Ai-910T formed a distinct phylogenetic lineage that reflects a new genus in the family Marinilabiliaceae, sharing high similarities to Alkaliflexus imshenetskii Z-7010T (92.78%), Alkalitalea saponilacus SC/BZ-SP2T (92.51%), and Geofilum rubicundum JAM-BA0501T (92.36%). Genomic similarity (average nucleotide identity and digital DNA-DNA hybridization) values between strain Ai-910T and its phylogenetic neighbors were below 65.27 and 16.90%, respectively, indicating that strain Ai-910T represented a novel species. The average amino acid identity between strain Ai-910T and other related members of the family Marinilabiliaceae were below 69.41%, supporting that strain Ai-910T was a member of a new genus within the family Marinilabiliaceae. Phylogenetic, genomic, and phenotypic analysis revealed that strain Ai-910T was distinguished from other phylogenetic relatives within the family Marinilabiliaceae. The genome size was 3.10 Mbp, and the DNA G + C content of the isolate was 42.8 mol%. Collectively, differences of the phenotypic and phylogenetic features of strain Ai-910T from its close relatives suggest that strain Ai-910T represented a novel species in a new genus of the family Marinilabiliaceae, for which the name Xiashengella succiniciproducens gen. nov., sp. nov. was proposed. The type strain of Xiashengella succiniciproducens is Ai-910T (= CGMCC 1.17893T = KCTC 25,304T).

Association of preoperative neutrophil-lymphocyte ratios with the emergence delirium in pediatric patients after tonsillectomy and adenoidectomy: an observational prospective study.

PURPOSE: The study aimed to investigate potential risk factors for emergence delirium (ED) in pediatric patients after tonsillectomy and adenoidectomy (T&A). METHODS: This prospective, single-center observational study enrolled children aged 3-7 years who underwent T&A under general anesthesia. ED was assessed according to DSM-IV or V criteria. Receiver operating characteristic curve analysis was performed to evaluate the predicative and cut-off values of risk factors, including age, preoperative anxiety level, postoperative pain and neutrophil-lymphocyte ratio (NLR) for ED. Univariate and multivariate logistic regression analyses were performed to investigate risk factors for ED. RESULTS: 94 pediatric patients who underwent T&A were enrolled and 19 developed ED (an incidence of 25.3%). Receiver operating characteristic analysis indicated that preoperative NLR was a significant predictor of ED with a cut-off value of 0.8719 and an area under the curve (AUC) of 0.671 (95% confidence interval (CI) 0.546-0.796, P = 0.022). Preoperative NLR (< 0.8719) and postoperative pain were independent risk factors associated with ED (odds ratio: 0.168, 95% CI 0.033-0.858, P = 0.032; odds ratio: 7.298, 95% CI 1.563-34.083, P = 0.011) according to multivariate logistic regression analysis. CONCLUSIONS: Preoperative NLR level and postoperative pain were independent risk factors for ED in pediatric patients undergoing T&A.

Increased Circulating IL-32 Is Associated With Placenta Macrophage-derived IL-32 and Gestational Diabetes Mellitus.

OBJECTIVE: Placenta-derived inflammation plays a vital role in the pathophysiology of gestational diabetes mellitus (GDM). IL-32 is a novel pro-inflammatory cytokine and metabolic regulator involved in the development of metabolic disease. We investigated the effect of IL-32 in GDM. MATERIALS AND METHODS: First-trimester C-reactive protein (CRP) level was monitored in a case-control study of 186 women with GDM and 186 women without. Placental tissue was lysed and analyzed by high-resolution liquid chromatography-tandem mass spectrometry. Circulating level of inflammatory cytokines IL-32, IL-6, and TNF-α were measured by ELISA kits. The expression of placenta-derived macrophages, inflammatory cytokines, and related pathway proteins were assessed by reverse transcriptase-quantitative PCR, western blot, immunohistochemistry, or immunofluorescence. RESULTS: First-trimester CRP level in peripheral blood was closely associated with glucose and insulin resistance index and was an independent correlation with the development of GDM. High-resolution liquid chromatography-tandem mass spectrometry revealed that placenta-derived CRP expression was dramatically elevated in women with GDM. Interestingly, the expression of placenta-derived IL-32 was also increased and located in the macrophages of placental tissue. Meanwhile, the expression of IL-6, TNF-α, and p-p38 were up-regulated in the placental tissues with GDM. Either IL-6 or TNF-α was colocated with IL-32 in the placental tissue. Importantly, circulating IL-32 throughout pregnancy was increased in GDM and was related to placental-derived IL-32 expression, circulating IL-6, and TNF-α, glucose and insulin resistance index. CONCLUSION: Increased circulating IL-32 throughout pregnancy was closely associated with placenta macrophage-derived IL-32 expression and GDM. First trimester IL-32 level in peripheral blood may serve to predict the development of GDM.

Transcriptomic Analysis of THP-1 Cells Exposed by Monosodium Urate Reveals Key Genes Involved in Gout.

BACKGROUND: Gout is a common inflammatory arthritis, which is mainly caused by the deposition of monosodium urate (MSU) in tissues. Transcriptomics was used to explore the pathogenesis and treatment of gout in our work. OBJECTIVE: The objective of the study was to analyze and validate potential therapeutic targets and biomarkers in THP-1 cells that were exposed to MSU. METHODS: THP-1 cells were exposed to MSU. The inflammatory effect was characterized, and RNA-Seq analysis was then carried out. The differential genes obtained by RNA-Seq were analyzed with gene expression omnibus (GEO) series 160170 (GSE160170) gout-related clinical samples in the GEO database and gout-related genes in the GeneCards database. From the three analysis approaches, the genes with significant differences were verified by the differential genes' transcription levels. The interaction relationship of long non-coding RNA (lncRNA) was proposed by ceRNA network analysis. RESULTS: MSU significantly promoted the release of IL-1ß and IL-18 in THP-1 cells, which aggravated their inflammatory effect. Through RNA-Seq, 698 differential genes were obtained, including 606 differential mRNA and 92 differential `LncRNA. Cross-analysis of the RNA-Seq differential genes, the GSE160170 differential genes, and the gout-related genes in GeneCards revealed a total of 17 genes coexisting in the tripartite data. Furthermore, seven differential genes-C-X-C motif chemokine ligand 8 (CXCL8), C-X-C motif chemokine ligand 2 (CXCL2), tumor necrosis factor (TNF), C-C motif chemokine ligand 3 (CCL3), suppressor of cytokine signaling 3 (SOCS3), oncostatin M (OSM), and MIR22 host gene (MIR22HG)-were verified as key genes that analyzed the weight of genes in pathways, the enrichment of inflammationrelated pathways, and protein-protein interaction (PPI)nodes combined with the expression of genes in RNA-Seq and GSE160170. It is suggested that MIR22HG may regulate OSM and SOCS3 through microRNA 4271 (miR-4271), OSM, and SOCS3m; CCL3 through microRNA 149-3p (miR-149-3p); and CXCL2 through microRNA 4652-3p (miR-4652-3p). CONCLUSION: The potential of CXCL8, CXCL2, TNF, CCL3, SOCS3, and OSM as gout biomarkers and MIR22HG as a therapeutic target for gout are proposed, which provide new insights into the mechanisms of gout biomarkers and therapeutic methods.

Clonal Propagation and Assessment of Biomass Production and Saponin Content of Elite Accessions of Wild Paris polyphylla var. yunnanensis.

Paris polyphylla var. yunnanensis is an endangered medicinal plant endemic to China with great economic importance for the pharmaceutical industry. Two significant barriers to its commercial development are the long duration of its seed germination and the frequency of interspecific hybridization. We developed a method for clonal propagation of Paris polyphylla var. yunnanensis and successfully applied it to selected elite wild plants, which could become cultivar candidates based on their biomass production and saponin content. In comparison to the traditional method, somatic embryogenesis produced an average of 63 somatic embryos per gram of callus in just six weeks, saving 12 to 15 months in plantlet production. The produced in vitro plantlets were strong and healthy and 94% survived transplanting to soil. Using this method, four candidate cultivars with diverse morphologies and geographic origins were clonally reproduced from selected elite wild accessions. In comparison to those obtained with the traditional P. polyphylla propagation technique, they accumulated higher biomass and polyphyllin levels in rhizomes plus adventitious roots during a five-year period. In conclusion, somatic embryogenesis-based methods offer an alternate approach for the rapid and scaled-up production of P. polyphylla, as well as opening up species conservation options.

Gut microbiome and serum short-chain fatty acids are associated with responses to chemo- or targeted therapies in Chinese patients with lung cancer.

Background: The association between gut microbes and short-chain fatty acids (SCFAs) and therapeutic responses of patients with lung cancer (LC) receiving therapy remains unknown. Methods: Fecal and serum samples were prospectively collected from patients with LC, classified as responders, if they presented durable clinical benefits, and non-responders, if not. The composition of gut microbes was analyzed using 16S ribosomal DNA sequencing. Serum SCFA concentrations were detected using gas chromatography. Cell proliferation, migration, invasion, cell cycle, and apoptosis assays were performed on isobutyric acid-treated A549 cells. Reverse transcription-quantitative PCR, Western blotting, immunocytochemistry, and immunofluorescence staining experiments have been performed to investigate the expression of associated genes or proteins. Results: Non-responders harbored higher microbiome α-diversity but lower ß-diversity compared with responders. Compared to the patients with low α-diversity, those with high α-diversity showed significantly shorter progression-free survival. Additionally, ß-diversity has also been observed between these two groups. Specifically, Parasutterella, Clostridiaceae, and Prevotella_7 were more abundant among responders, whereas Bacteroides_stercoris and Christensenellaceae_R-7_group were more abundant in non-responders. The serum SCFA (especially acetate and isobutyrate) levels tended to be higher in responders. Isobutyric acid inhibited the proliferation, migration, and invasion of A549 cells by inducing apoptosis and G1/S arrest while upregulating the expression of GPR41, GPR43, and GPR5C and downregulating that of PAR1, and increasing the activity of histone acetyltransferases. Conclusion: We revealed the influence of gut microbiota and SCFAs on the therapeutic responses in patients with LC and the anti-tumor effect of isobutyric acid, indicating their potential use as therapeutic targets.

Study on the effect of self-made fracture positioning compression guide device for posterior malleolus fracture surgery: Medical prevention.

To evaluate the effectiveness of a self-designed pressure-guided fracture positioning device, a prospective study was conducted in patients with posterior ankle fractures undergoing surgery using the device. Twenty-seven cases of ankle joint fracture with posterior malleolus fracture were treated by surgery. In the process of fixing posterior malleolus fracture, a self-designed fracture positioning compression guide device was used to fix posterior malleolus bone by anterior and posterior approaches. Postoperative CT images were used to assess the fixation position as well as length of the screw and the compression of the fracture. All patients had healed ankle fractures, and the anterior-posterior screws were fixed in the central area of the posterior malleolus. Posterior malleolus fragment displacement was <2 mm. The screw effectively secured the cortex beyond the length of the posterior malleolus cortex by no more than two threads. The good rate of ankle joint function was 85.16%. Compared to traditional surgical techniques, minimally invasive fixation using the self-designed positioning compression guide device has several advantages, including smaller trauma, faster postoperative recovery, and improved patient satisfaction. The device also provides the surgeon with greater control and precision during the surgical procedure, which can contribute to better surgical outcomes.

Roles of protein post-translational modifications in glucose and lipid metabolism: mechanisms and perspectives.

The metabolism of glucose and lipids is essential for energy production in the body, and dysregulation of the metabolic pathways of these molecules is implicated in various acute and chronic diseases, such as type 2 diabetes, Alzheimer's disease, atherosclerosis (AS), obesity, tumor, and sepsis. Post-translational modifications (PTMs) of proteins, which involve the addition or removal of covalent functional groups, play a crucial role in regulating protein structure, localization function, and activity. Common PTMs include phosphorylation, acetylation, ubiquitination, methylation, and glycosylation. Emerging evidence indicates that PTMs are significant in modulating glucose and lipid metabolism by modifying key enzymes or proteins. In this review, we summarize the current understanding of the role and regulatory mechanisms of PTMs in glucose and lipid metabolism, with a focus on their involvement in disease progression associated with aberrant metabolism. Furthermore, we discuss the future prospects of PTMs, highlighting their potential for gaining deeper insights into glucose and lipid metabolism and related diseases.

Nighttime hypoxia effects on ATP availability for photosynthesis in seagrass.

Hypoxia is a major emerging threat to coastal ecosystems, which is closely related to the decline in seagrass meadows, but its damage mechanism is still unclear. This study found that hypoxia at night significantly reduced the photosynthetic capacity of Enhalus acoroides after reillumination. Photosystem II (PSII) was damaged by high-light stress during daytime low-tide exposure, but high-light-damaged PSII of E. acoroides could recover part of its activity indark normoxic seawater to maintain the normal operation of photosynthesis after reillumination during the next day. However, hypoxia inhibited the recovery of damaged PSII under darkness. By transcriptomic analysis and inhibitor verification experiments, dark hypoxia was shown to inhibit respiration, thereby reducing ATP production and preventing ATP from being transported into chloroplasts, which, in turn, led to an insufficient supply of energy required for PSII to recover. This study demonstrated that hypoxia has several negative impacts on the photosynthetic apparatus of E. acoroides at night reducing photosynthetic capacity after reillumination, which may be an important factor leading to the decline of the seagrass meadows.

Identification of key genes in HER2-positive breast cancer with brain metastasis via bioinformatics methods.

Background: Brain metastasis (BM) represents one of the most common advanced disease states in breast cancer (BC), especially in human epidermal growth factor receptor 2 (HER2)-positive BC, and is associated with poor survival outcomes. Methods: In this study, in-depth analysis of the microarray data from the GSE43837 dataset with 19 BM samples of HER2-positive BC patients and 19 HER2-positive nonmetastatic primary BC samples was conducted. The differentially expressed genes (DEGs) between BM and primary BC samples were identified and function enrichment analysis of the DEGs was conducted to identify potential biological functions. The hub genes were identified by constructing the protein-protein interaction (PPI) network using STRING and Cytoscape. UALCAN and Kaplan-Meier plotter online tools were used to verify the clinical roles of the hub DEGs in HER2-positive BC with BM (BCBM). Results: A total of 1,056 DEGs including 767 downregulated and 289 upregulated genes were identified by comparing the microarray data of the HER2-positive BM and primary BC samples. Functional enrichment analysis demonstrated that the DEGs were mainly enriched in pathways related to extracellular matrix (ECM) organization, cell adhesion, and collagen fibril organization. PPI network analysis identified 14 hub genes. Among these, CD44, COL1A2, MMP14, POSTN, and SOX9 were associated with the survival outcomes of HER2-positive patients. Conclusions: In summary, 5 BM-specific hub genes were identified in the study; those are potential prognostic biomarkers and therapeutic targets for HER2-positive BCBM patients. However, further investigations are necessary to unravel the mechanisms by which these 5 hub genes regulate BM in HER2-positive BC.

Kcnma1 is involved in mitochondrial homeostasis in diabetes-related skeletal muscle atrophy.

Uncontrolled diabetes causes a catabolic state with multi-organic complications, of which impairment on skeletal muscle contributes to the damaged mobility. Kcnma1 gene encodes the pore-forming α-subunit of Ca2+ - and voltage-gated K+ channels of large conductance (BK channels), and loss-of-function mutations in Kcnma1 are in regards to impaired myogenesis. Herein, we observed a time-course reduction of Kcnma1 expression in the tibialis anterior muscles of leptin receptor-deficient (db/db) diabetic mice. To investigate the role of Kcnma1 in diabetic muscle atrophy, muscle-specific knockdown of Kcnma1 was achieved by mice receiving intravenous injection of adeno-associated virus-9 (AAV9)-encoding shRNA against Kcnma1 under the muscle creatine kinase (MCK) promoter. Impairment on muscle mass and myogenesis were observed in m/m mice with AAV9-shKcnma1 intervention, while this impairment was more obvious in diabetic db/db mice. Simultaneously, damaged mitochondrial dynamics and biogenesis showed much severer in db/db mice with AAV9-shKcnma1 intervention. RNA sequencing revealed the large transcriptomic changes resulted by Kcnma1 knockdown, and changes in mitochondrial homeostasis-related genes were validated. Besides, the artificial alteration of Kcnma1 in mouse C2C12 myoblasts was achieved with an adenovirus vector. Consistent results were demonstrated by Kcnma1 knockdown in palmitate-treated cells, whereas opposite results were exhibited by Kcnma1 overexpression. Collectively, we document Kcnma1 as a potential keeper of mitochondrial homeostasis, and the loss of Kcnma1 is a critical event in priming skeletal muscle loss in diabetes.

A biomimetic beetle-like membrane with superoleophilic SiO2-induced oil coalescence on superhydrophilic CuC2O4 nanosheet arrays for effective O/W emulsion separation.

It is highly attractive to develop highly efficient oil-in-water (O/W) emulsion separation technologies for promoting the oily wastewater treatment. Herein, a novel inversely Stenocara beetle-like hierarchical structure of superhydrophobic SiO2 nanoparticle-decorated CuC2O4 nanosheet arrays were prepared on copper mesh membrane by bridging polydopamine (PDA) to make a SiO2/PDA@CuC2O4 membrane for substantially enhanced separation of O/W emulsions. The superhydrophobic SiO2 particles on the as-prepared SiO2/PDA@CuC2O4 membranes were served as localized active sites to induce coalescence of small-size oil droplets in oil-in-water (O/W) emulsions. Such innovated membrane delivered outstanding demulsification ability of O/W emulsion with a high separation flux of 2.5 kL⋅m-2⋅h-1 and its filtrate's chemical oxygen demand (COD) being 30 and 100 mg⋅L-1 for surfactant-free emulsion (SFE) and surfactant-stabilized emulsion (SSE), respectively, and also exhibited a good anti-fouling performance in cycling tests. The innovative design strategy developed in this work broadens the application of superwetting materials for oil-water separation and presents a promising prospect in practical oily wastewater treatment applications.

Serum glycoprotein non-metastatic melanoma protein B (GPNMB) level as a potential biomarker for diabetes mellitus-related cataract: A cross-sectional study.

Background: Diabetes mellitus (DM), a metabolic disease that has attracted significant research and clinical attention over the years, can affect the eye structure and induce cataract in patients diagnosed with DM. Recent studies have indicated the relationship between glycoprotein non-metastatic melanoma protein B (GPNMB) and DM and DM-related renal dysfunction. However, the role of circulating GPNMB in DM-associated cataract is still unknown. In this study, we explored the potential of serum GPNMB as a biomarker for DM and DM-associated cataract. Methods: A total of 406 subjects were enrolled, including 60 and 346 subjects with and without DM, respectively. The presence of cataract was evaluated and serum GPNMB levels were measured using a commercial enzyme-linked immunosorbent assay kit. Results: Serum GPNMB levels were higher in diabetic individuals and subjects with cataract than in those without DM or cataract. Subjects in the highest GPNMB tertile group were more likely to have metabolic disorder, cataract, and DM. Analysis performed in subjects with DM elucidated the correlation between serum GPNMB levels and cataract. Receiver operating characteristic (ROC) curve analysis also indicated that GPNMB could be used to diagnose DM and cataract. Multivariable logistic regression analysis illustrated that GPNMB levels were independently associated with DM and cataract. DM was also found to be an independent risk factor for cataract. Further surveys revealed the combination of serum GPNMB levels and presence of DM was associated with a more precise identification of cataract than either factor alone. Conclusions: Increased circulating GPNMB levels are associated with DM and cataract and can be used as a biomarker of DM-associated cataract.

Non-coding RNAs in metabolic reprogramming of bone and soft tissue sarcoma: Fundamental mechanism and clinical implication.

Sarcomas, comprising approximately 1% of human malignancies, show a poor response to treatment and easy recurrence. Metabolic reprogramming play an important role in tumor development in sarcomas. Accumulating evidence shows that non-coding RNAs (ncRNAs) participate in regulating the cellular metabolism of sarcomas, which improves the understanding of the development of therapy-resistant tumors. This review addresses the regulatory roles of metabolism-related ncRNAs and their implications for sarcoma initiation and progression. Dysregulation of metabolism-related ncRNAs is common in sarcomas and is associated with poor survival. Emerging studies show that abnormal expression of metabolism-related ncRNAs affects cellular metabolism, including glucose, lipid, and mitochondrial metabolism, and leads to the development of aggressive sarcomas. This review summarizes recent advances in the roles of dysregulated metabolism-related ncRNAs in sarcoma development and stemness and describes their potential to serve as biological biomarkers for disease diagnosis and prognosis prediction, as well as therapeutic targets for treating refractory sarcomas.

["Component-target-efficacy" network analysis and experimental verification of Qingkailing Oral Preparation].

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.