ECM Microenvironment in Vascular Homeostasis: New Targets for Atherosclerosis.

Alterations in vascular extracellular matrix (ECM) components, interactions, and mechanical properties influence both the formation and stability of atherosclerotic plaques. This review discusses the contribution of the ECM microenvironment in vascular homeostasis and remodeling in atherosclerosis, highlighting Cartilage oligomeric matrix protein (COMP) and its degrading enzyme ADAMTS7 as examples, and proposes potential avenues for future research aimed at identifying novel therapeutic targets for atherosclerosis based on the ECM microenvironment.

Low temperature inhibits anthocyanin accumulation in strawberry fruit by activating FvMAPK3-induced phosphorylation of FvMYB10 and degradation of Chalcone Synthase 1.

Low temperature causes poor coloration of strawberry (Fragaria sp.) fruits, thus greatly reducing their commercial value. Strawberry fruits accumulate anthocyanins during ripening, but how low temperature modulates anthocyanin accumulation in plants remains largely unknown. We identified MITOGEN-ACTIVATED PROTEIN KINASE3 (FvMAPK3) as an important negative regulator of anthocyanin accumulation that mediates the poor coloration of strawberry fruits in response to low temperature. FvMAPK3 activity was itself induced by low temperature, leading to the repression of anthocyanin accumulation via two mechanisms. Activated FvMAPK3 acted as the downstream target of MAPK KINASE4 (FvMKK4) and SUCROSE NONFERMENTING1-RELATED KINASE2.6 (FvSnRK2.6) to phosphorylate the transcription factor FvMYB10 and reduce its transcriptional activity. In parallel, FvMAPK3 phosphorylated CHALCONE SYNTHASE1 (FvCHS1) to enhance its proteasome-mediated degradation. These results not only provide an important reference to elucidate the molecular mechanisms underlying low-temperature-mediated repression of anthocyanin accumulation in plants, but also offer valuable candidate genes for generating strawberry varieties with high tolerance to low temperature and good fruit quality.

Visible-light-induced tandem reaction of quinoxalin-2(1H)-ones, alkenes, and sulfonyl chlorides.

A visible-light-induced tandem reaction involving quinoxalin-2(1H)-ones, alkenes, and sulfonyl chlorides, catalyzed by 4CzIPN, was developed. The utilization of easily accessible sulfonyl chlorides, metal-free conditions, and a wide substrate scope established this protocol as an efficient and alternative method for obtaining sulfonated quinoxalin-2(1H)-ones.

Quercetin prevented diabetic nephropathy by inhibiting renal tubular epithelial cell apoptosis via the PI3K/AKT pathway.

Diabetic nephropathy (DN) is the most common and serious complication of diabetes, posing a significant threat to human health. Currently, safe and effective preventive strategies for DN are lacking. The study aimed to explore the preventive effect and the underlying mechanism of quercetin against DN. In the in vivo experiments, we established a mouse model of type 2 diabetes mellitus (T2DM) induced by a combination of high-fat diet (HFD) and streptozotocin (STZ) to explore the preventive effect of quercetin on DN and its protective role against renal tubular epithelial cell apoptosis. Subsequently, in vitro experiments using human tubular epithelial cells (HK-2 cells) were conducted to further validate the protective effects of quercetin on renal tubular epithelial cell apoptosis. Additionally, we employed RNA sequencing analysis (RNA-seq) and network pharmacology analysis to comprehensively elucidate the molecular mechanisms involved. In vivo, we observed a significant increase in the ratio of urinary microalbumin to creatinine in diabetic mice compared to control mice, accompanied by the activation of renal tubular epithelial cell apoptosis. Remarkably, all of these changes were reversed after quercetin treatment. In vitro, high-glucose-induced apoptosis in HK-2 cells was significantly attenuated by quercetin. Subsequent RNA sequencing analysis and network pharmacology analysis revealed that quercetin was most likely to inhibit high-glucose-induced HK-2 cell apoptosis through the PI3K/AKT signaling pathway. Western Blotting results further demonstrated that quercetin could inhibit the activation of the PI3K/AKT signaling pathway in HK-2 cells induced by high glucose. Our results supported that quercetin could prevent DN by inhibiting tubular epithelial cell apoptosis via the PI3K/AKT pathway. Quercetin might be a promising candidate for the prevention of DN.

The immune landscape and prognostic analysis of CXCL8 immune-related genes in cervical squamous cell carcinoma.

Cervical squamous cell carcinoma (CESC), one of the most common malignancies in women, imposes a significant burden on women's health worldwide. Despite extensive research, the molecular and pathogenic mechanisms of cervical squamous cell carcinoma and CESC remain unclear. This study aimed to explore the immune-related genes, immune microenvironment infiltration, and prognosis of CESC, providing a theoretical basis for guiding clinical treatment. Initially, by mining four gene sets and immune-related gene sets from public databases, 14 immune-related genes associated with CESC were identified. Through univariate and multivariate COX regression analyses, as well as lasso regression analysis, four CESC-independent prognostic genes were identified, and a prognostic model was constructed, dividing them into high and low-risk groups. The correlation between these genes and immune cells and immune functions were explored through ssGSEA enrichment analysis, revealing a close association between the high-risk group and processes such as angiogenesis and epithelial-mesenchymal transition. Furthermore, using public databases and qRT-PCR experiments, significant differences in CXCL8 expression between normal cervical cells and cervical cancer cells were discovered. Subsequently, a CXCL8 knockdown plasmid was constructed, and the efficiency of CXCL8 knockdown was validated in two CESC cell lines, MEG-01 and HCE-1. Through CCK-8, scratch, and Transwell assays, it was confirmed that CXCL8 knockdown could inhibit the proliferation, invasion, and migration abilities of CESC cells. Targeting CXCL8 holds promise for personalized therapy for CESC, providing a strong theoretical basis for achieving clinical translation.

Competition-Based Two-Dimensional Photonic Crystal Dually Cross-Linked Supramolecular Hydrogel for Colorimetric and Fluorescent Dual-Mode Sensing of Bisphenol A.

Bisphenol A (BPA), one of the most abundantly produced endocrine disrupting chemicals, is widely used in everyday plastic products and thus must be monitored. Multimode sensing platforms are able to combine the advantages of different strategies while solving the issues of inaccurate test results of single signal sensing. However, the exploration in this field is limited due to the compromise of sensing conditions and inevitable mutual interferences of different systems. Herein, we constructed a two-dimensional photonic crystal dually cross-linked supramolecular hydrogel (2DPCDCSH) by utilizing a host-guest pair of ß-cyclodextrin (ß-CD) and tert-butyl (t-Bu) as the second cross-linking for colorimetric and fluorescent dual-mode sensing of BPA. Based on the fact that BPA can act as a competitive guest to break the host-guest interaction between ß-CD and t-Bu, the cross-linking density decreased and an expansion-induced structural color change occurred. Sensitive and selective BPA detection can be easily achieved by measuring the Debye diffraction ring diameter or observing the color change of 2DPC with a detection limit of 1 µg mL-1. Moreover, the formation of the ß-CD/BPA complex gave a significant enhancement of the intrinsic fluorescence of BPA, obtaining a detection limit of 0.001 µg mL-1. The two sensing systems can share the same reaction condition and yield a wider dynamic response range than the single signal strategy. Overall, the proposed method presented an efficient, rapid, cost-effective, and regenerative dual-mode method for BPA analysis and shed new insights for the design of diversified sensing platforms.

SnRK2 subfamily I protein kinases regulate ethylene biosynthesis by phosphorylating HB transcription factors to induce ACO1 expression in apple.

Ethylene (ETH) controls climacteric fruit ripening and can be triggered by osmotic stress. However, the mechanism regulating ETH biosynthesis during fruit ripening and under osmotic stress is largely unknown in apple (Malus domestica). Here, we explored the roles of SnRK2 protein kinases in ETH biosynthesis related to fruit ripening and osmoregulation. We identified the substrates of MdSnRK2-I using phosphorylation analysis techniques. Finally, we identified the MdSnRK2-I-mediated signaling pathway for ETH biosynthesis related to fruit ripening and osmoregulation. The activity of two MdSnRK2-I members, MdSnRK2.4 and MdSnRK2.9, was significantly upregulated during ripening or following mannitol treatment. Overexpression of MdSnRK2-I increased ETH biosynthesis under normal and osmotic conditions in apple fruit. MdSnRK2-I phosphorylated the transcription factors MdHB1 and MdHB2 to enhance their protein stability and transcriptional activity on MdACO1. MdSnRK2-I also interacted with MdACS1 and increased its protein stability through two phosphorylation sites. The increased MdACO1 expression and MdACS1 protein stability resulted in higher ETH production in apple fruit. In addition, heterologous expression of MdSnRK2-I or manipulation of SlSnRK2-I expression in tomato (Solanum lycopersicum) fruit altered fruit ripening and ETH biosynthesis. We established that MdSnRK2-I functions in fruit ripening and osmoregulation, and identified the MdSnRK2-I-mediated signaling pathway controlling ETH biosynthesis.

Curcumin enhances drug sensitivity of gemcitabine-resistant lung cancer cells and inhibits metastasis.

This study aimed to investigate the effects of curcumin (Cur) on the proliferation, migration, and invasion of gemcitabine (GEM) resistant lung cancer A549 cells (A549/GEM), and the potential mechanism. After treating with GEM, individually or combined with Cur, the inhibition, migration, and invasion of A549/GEM were tested by the CCK8, transwell, and cell wound healing assays, respectively. QRT-PCR and Western blot were used to detect mRNA and protein markers. Finally, the therapeutic effects of GEM, individually or combined with Cur, were verified in nude mice. The results indicated that the combined application of Cur and GEM can improve the sensitivity of A549/GEM to the GEM. Compared with the GEM, GEM plus Cur significantly decreased the migration and invasion of A549/GEM cells. The expression levels of MMP9 , Vimentin, and N-cadherin were significantly decreased, while the E-cadherin expression was increased. In vivo experiments showed a better therapeutic effect of GEM combined with Cur than that of GEM alone, and the combination therapy did not cause more toxicity to animals. In summary, Cur reversed GEM resistance and inhibited the EMT process in A549/GEM cells. GEM, combined with Cur, is safe and more effective in the treatment of non-small cell lung cancer.

Protective role of overexpressed MUC5AC against fibrosis in MHV-68-induced combined pulmonary fibrosis and emphysema mouse model.

Mucins have long been regarded to play a role as a barrier to prevent mucosal infections; however, some studies report that overexpression of mucins induces obstruction and inflammation of airways. We investigated whether the secretion of overexpressed mucin, mucin5ac (MUC5AC), could improve protection against pathogens. To examine the possible roles of mucin hypersecretion in augmenting host defense against disease-promoting muco-obstructive lung disease, a mouse model that overexpressed MUC5AC was generated. We had previously proved that murine gammaherpesvirus-68 (MHV-68) infection could induce emphysema in mice, which later developed into combined pulmonary fibrosis and emphysema (CPFE). We further explored whether increased MUC5AC secretion could provide benefits against MHV-68 induced fibrosis. We initially developed a pcDNA3.1-MUC5AC mouse model. Next, the experimental mice were randomly divided into five groups: normal control, pcDNA3.1 control, pcDNA3.1-MUC5AC, CPFE, and pcDNA3.1- MUC5AC + CPFE. Morphometric analysis of each group was performed by hematoxylin and eosin staining and Masson trichrome staining. MUC5AC levels in lung tissues were analyzed by immunohistochemical staining, real-time polymerase chain reaction, and Western blot analysis. The airway inflammation was determined by differential cell counts of bronchoalveolar lavage fluid (BALF) and measurement of cytokines and chemokines in BALF by enzyme-linked immunosorbent assay. MUC5AC hypersecretion alone was not sufficient to drive goblet cell metaplasia to induce obvious mucus plugging and airway inflammation. However, MUC5AC overexpression served as a protective barrier against MHV-68 virus infection in vivo. Infectivity of MHV-68 was decreased in the pcDNA3.1-MUC5AC + CPFE group compared with that in CPFE group. Meanwhile, a reduction of MHV-68 virus attenuated the expressions of chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-X-C motif) ligand 5 (CXCL5), interleukin-13 (IL-13), and transforming growth factor-ß1 (TGF-ß1), and weakened airway inflammation and fibrosis in the pcDNA3.1-MUC5AC + CPFE group. Overexpression of MUC5AC appears to exhibit a protective role against MHV-68 infection in mice with emphysema that subsequently developed into CPFE and to further decrease airway inflammation and fibrosis induced by MHV-68 by decreasing the expressions of CCL2, CXCL5, IL-13, and TGF-ß1.

Epidemiological and phylogenetic analysis of canine kobuviruses in Tangshan, China.

Canine kobuviruses (CaKoV) have been found in healthy and diarrheic dogs as well as asymptomatic wild carnivores in various countries. In order to investigate the prevalence and evolution of CaKoV in Tangshan, China, 82 dog fecal samples from pet hospitals in Tangshan were subjected to RT-PCR targeting a segment of the 3D gene of CaKoV. Using this method, we identified CaKoV in 14 samples (17.07%, 14/82). Of the CaKoV-positive samples, 78.57% (11/14) and 50% (7/14) were positive for canine parvovirus and canine coronavirus, respectively. The nucleotide sequences of the 14 strains 96.6%-100% identical to each other and 77.6%-99.2% identical to representative sequences from the NCBI GenBank database. We also amplified the 14 VP1 gene sequences and found that they were 93.3%-99.6% identical to each other and 73.3%-97.8% identical to representative sequences from the NCBI GenBank database. Phylogenetic analysis revealed that the 14 CaKoV strains from Tangshan are closely related to those identified in China and Thailand and display less similarity to those found in Africa, the United States, and Europe. Our data suggest that CaKoV circulated in young pet dogs in Tangshan and displays a high co-infection rate with CCoV and CPV. However, the relationship between the three viruses and their roles in the host requires further investigation.

Hydrogen bond, ring tension and π-conjugation effects: methyl and vinyl substitutions dramatically change the photodynamics of Criegee intermediates.

The substitution effect in chemistry is a concept that is probably too common to mention, while for a molecule with an elusive electronic structure, substitution can introduce an unusual effect that dramatically tunes the chemical process. To reveal the substitution effects on the photodynamics of Criegee Intermediates (CIs), we carried out the multireference CASSCF trajectory surface-hopping (TSH) molecular dynamics and CASPT2 electronic-structure calculations for a methyl-substituted CI (MCI) and a vinyl-substituted CI (VCI). The results show that for different substituents, the hydrogen bond, ring tension and π-conjugation not only alter the relative stabilities of the conformers/configurations, but also dramatically change the photo-induced channel of CIs. For an anti-MCI, the dominant channel starting from the S1 state is the ring-closure process leading to dioxirane, while in the syn configuration, the intramolecular CHO hydrogen bond hinders the rotation around the C-O bond and thus leads to a high yield of in-plane O-O dissociation towards acetaldehyde (X1A') and the O(1D) atom. In a VCI with an unsaturated substituent, the π-conjugation greatly strengthens the O-O bond and therefore no O-O dissociation is observed in all configurations. In addition, the CHO hydrogen bond in the syn(CO)-VCI further stabilizes the S1-state intermediates and makes them less reactive; in contrast, isomerization to dioxirane becomes the globally dominant channel in the anti(CO)-VCI. The dramatic substitution effects by saturated and unsaturated substituents on CIs found here will deepen the understanding of Criegee-intermediate chemistry.

Functional exploration of the IFT-A complex in intraflagellar transport and ciliogenesis.

Intraflagellar transport (IFT) particles or trains are composed of IFT-A and IFT-B complexes. To assess the working mechanism of the IFT-A complex in IFT and ciliogenesis, we have analyzed ift43 mutants of Chlamydomnonas in conjunction with mutants of the other IFT-A subunits. An ift43 null mutant or a mutant with a partial deletion of the IFT43 conserved domain has no or short flagella. The mutants accumulate not only IFT-B but also IFT-Ain the short flagella, which is in contrast to an ift140 null mutant. The IFT43 conserved domain is necessary and sufficient for the function of IFT43. IFT43 directly interacts with IFT121 and loss of IFT43 results in instability of IFT-A. A construct with a partial deletion of the IFT43 conserved domain is sufficient to rescue the instability phenotype of IFT-A, but results in diminishing of IFT-A at the peri-basal body region. We have further provided evidence for the direct interactions within the IFT-A complex and shown that the integrity of IFT-A is important for its stability and cellular localization. Finally, we show that both IFT43 and IFT140 are involved in mobilizing ciliary precursors from the cytoplasmic pool during flagellar regeneration, suggesting a novel role of IFT-A in transporting ciliary components in the cytoplasm to the peri-basal body region.

Conserved gene regulatory module specifies lateral neural borders across bilaterians.

The lateral neural plate border (NPB), the neural part of the vertebrate neural border, is composed of central nervous system (CNS) progenitors and peripheral nervous system (PNS) progenitors. In invertebrates, PNS progenitors are also juxtaposed to the lateral boundary of the CNS. Whether there are conserved molecular mechanisms determining vertebrate and invertebrate lateral neural borders remains unclear. Using single-cell-resolution gene-expression profiling and genetic analysis, we present evidence that orthologs of the NPB specification module specify the invertebrate lateral neural border, which is composed of CNS and PNS progenitors. First, like in vertebrates, the conserved neuroectoderm lateral border specifier Msx/vab-15 specifies lateral neuroblasts in Caenorhabditis elegans Second, orthologs of the vertebrate NPB specification module (Msx/vab-15, Pax3/7/pax-3, and Zic/ref-2) are significantly enriched in worm lateral neuroblasts. In addition, like in other bilaterians, the expression domain of Msx/vab-15 is more lateral than those of Pax3/7/pax-3 and Zic/ref-2 in C. elegans Third, we show that Msx/vab-15 regulates the development of mechanosensory neurons derived from lateral neural progenitors in multiple invertebrate species, including C. elegans, Drosophila melanogaster, and Ciona intestinalis We also identify a novel lateral neural border specifier, ZNF703/tlp-1, which functions synergistically with Msx/vab-15 in both C. elegans and Xenopus laevis These data suggest a common origin of the molecular mechanism specifying lateral neural borders across bilaterians.

Diffusion kurtosis imaging in sacroiliitis to evaluate the activity of ankylosing spondylitis.

BACKGROUND: Conventional magnetic resonance (MR) imaging is limited in providing sufficient information on microstructure or in quantitatively evaluating certain inflammation processes. Functional MR sequences such as diffusion kurtosis imaging (DKI) might help to evaluate the sacroiliac joint in ankylosing spondylitis (AS) patients. PURPOSE: To explore the application of DKI in evaluating the disease activity of AS. STUDY TYPE: Prospective. POPULATION: Forty-four patients with a diagnosis of AS according to the Assessment in SpondyloArthritis International Society (ASAS) criteria. FIELD STRENGTH/SEQUENCE: 3.0T MRI including the DKI sequence (b = 0, 500, 1000, 1500, 2000 s/mm2 ). STATISTICAL TESTS: Two-independent-samples t-test and one-way analysis of variance (ANOVA) were used to compare the DKI parameters among different groups, and post-hoc Scheffe's method was adopted. Receiver operating characteristic (ROC) analysis and Spearman's rank correlation were performed to test the diagnostic performance of DKI parameters in distinguishing different activity grades and the correlation between them, respectively. ASSESSMENT: AS disease activity was evaluated according to the Ankylosing Spondylitis Disease Activity Score (ASDAS), and four disease activity states were chosen by consensus: inactive disease and moderate, high, and very high disease activity. The three cutoffs selected to separate these states were: 1.3, 2.1, and 3.5 units, respectively. RESULTS: The corrected ADC (D) and apparent diffusion coefficient (ADC) values of sacroiliac joints in the active group were significantly higher, while the the kurtosis of diffusion (K value) value was significantly lower than those of the inactive group (all P < 0.001). The D value performed best in distinguishing different activity grades (all P < 0.001). The D and ADC values correlated positively, while the K value correlated negatively, with activity grade significantly (r = 0.918, 0.798, and -0.765, respectively; all P < 0.001). DATA CONCLUSION: DKI of sacroiliac joints might be useful to evaluate the disease activity of AS. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:101-108.

Involvement of budding yeast Rad5 in translesion DNA synthesis through physical interaction with Rev1.

DNA damage tolerance (DDT) is responsible for genomic stability and cell viability by bypassing the replication block. In Saccharomyces cerevisiae DDT employs two parallel branch pathways to bypass the DNA lesion, namely translesion DNA synthesis (TLS) and error-free lesion bypass, which are mediated by sequential modifications of PCNA. Rad5 has been placed in the error-free branch of DDT because it contains an E3 ligase domain required for PCNA polyubiquitination. Rad5 is a multi-functional protein and may also play a role in TLS, since it interacts with the TLS polymerase Rev1. In this study we mapped the Rev1-interaction domain in Rad5 to the amino acid resolution and demonstrated that Rad5 is indeed involved in TLS possibly through recruitment of Rev1. Genetic analyses show that the dual functions of Rad5 can be separated and reconstituted. Crystal structure analysis of the Rad5-Rev1 interaction reveals a consensus RFF motif in the Rad5 N-terminus that binds to a hydrophobic pocket within the C-terminal domain of Rev1 that is highly conserved in eukaryotes. This study indicates that Rad5 plays a critical role in pathway choice between TLS and error-free DDT.

[Effects of triptolide on the expression of androgen receptor in human prostate LNCaP cells and its mechanism of action].

To study the regulation of androgen receptor (AR) expression in human prostate cancer LNCaP cells by triptolide (TP) and the possible mechanism, by using qRT-PCR and Western blot, the AR mRNA and protein levels in TP treated LNCaP cells were detected, and the AR protein level in TP and NF-κB inhibitor treated LNCaP cells was also detected; a series of pGL3-AR promoter reporter gene vectors were built using restriction-free cloning method, and the vectors were employed to investigate the effects of TP on the transcriptional activity of AR promoter in LNCaP cells; the upstream proteins which may play regulatory roles were detected using western blot assay. After treated LNCaP cells with TP for 48 h, AR mRNA and protein expressions decreased with increasing TP concentration. The expression of AR target gene PART1 and prostate specific antigen (PSA) was also downregulated by TP treatment; a series of pGL3-AR promoter reporter vectors were constructed and validated by sequencing and luciferase activity; the results of dual luciferase reporter assay showed that TP downregulated AR at the transcriptional level; PI3K/AKT/NF-κB pathway which is associated with AR promoter activity was drowregulated by TP. In conclusion, our results demonstrated that the transcriptional activity of AR in LNCAP cells was downregulated by TP, and PI3K/AKT/NF-κB pathway may be involved in the regulation mechanism.

Research on the pharmacognostic characteristics, physicochemical properties and in vitro antioxidant potency of Rosa laxa Retz. flos.

Rosa laxa Retz. is an unexplored Rosaceae plant in Xinjiang, China, and its flower is traditionally used in Kazak to treat the common cold, fever, and epileptic seizures and lessen the effects of aging. In the present study, the pharmacognostic profiles, physicochemical properties, phytochemical characteristics, and in vitro antioxidant potency of Rosa laxa Retz. flos (RLF) were presented. In the pharmacognostic evaluation of RLF, organoleptic characteristics, internal structures, and powder information were observed, and physicochemical parameters, including moisture content, ash, pH value, swelling degree, and extractives were examined. The quantitative analysis of the chemical composition of four different polar extracts of RLF showed that the aqueous part had the highest total triterpene acid, flavonoid, and polyphenol content (4.50 ± 0.04 mg/g, 50.56 ± 0.03 mg/g, and 60.20 ± 0.09 mg/g, respectively). A high-performance liquid chromatography (HPLC)-diode array detector (DAD) method was established and the contents of gallic acid, ellagic acid, astragalin, and tiliroside in RLF were determined simultaneously. In the set concentration range, the linear relationship among the four components was good (r > 0.999), the average recoveries were 97.36%-100.54%. The contents of gallic acid, ellagic acid, astragalin, and tiliroside in RLF samples were (9.46 ± 2.31) mg/g, (10.60 ±0.75) mg/g, (1.13 ± 2.50) mg/g, and (1.11 ± 2.65) mg/g, respectively. The types of its secondary metabolites were determined by fluorescence, color reaction by chemical solvent method, and ultraviolet-visible (UV-Vis) spectroscopy. The functional groups of its secondary metabolites were determined by Fourier transform infrared (FTIR) spectroscopy. Results showed that RLF contains a variety of secondary metabolic products, including flavonoids, phenolic acid, glycoside, and organic acid. TLC identification showed it contains ursolic acid, ß-sitosterol, tiliroside, astragalin, isoquercitrin, kaempferol-3-O-rutinoside, gallic acid, and ellagic acid. The in vitro antioxidant activity of different polar parts of RLF was investigated by DPPH, ABTS, and reduction performance experiments. The aqueous extract had the strongest antioxidant capacity, consistent with the high content of triterpene acids, flavonoids, and polyphenolic compounds. These findings will provide critical information for the study of quality standards and medicinal value of RLF and its extracts, justify its usage in traditional medicinal systems, and encourage the use of this plant in disease prevention and treatment. Its phytochemical composition and pharmacological studies need to be explored in future. RESEARCH HIGHLIGHTS: Optical microscope and scanning electron microscope (SEM) were used to observe the morphology, and microstructure of Rosa laxa Retz. flos (RLF). The physicochemical properties, fluorescence and phytochemical composition of four different polar extracts of RLF were analyzed by UV-Vis and FTIR. Determination of total triterpenic acid, total flavonoids, and total polyphenols in four different polar extracts of RLF by UV spectrophotometry. A high-performance liquid chromatography (HPLC)-diode array detector (DAD) method was established and the contents of gallic acid, ellagic acid, astragalin, and tiliroside in RLF were determined simultaneously. TLC confirmed that RLF contains ursolic acid, ß-sitosterol, tiliroside, astragalin, isoquercitrin, kaempferol 3-rutinoside, gallic acid, and ellagic acid. The in vitro antioxidant activity of RLF was studied by DPPH, ABTS, and reducing ability experiments.

Investigation on the anti-α-glucosidase mechanism of aspergillus triazolate A from Oxalis corniculate L.

Diabetes mellitus characterized by abnormal glucose concentration is a metabolic disease. α-Glu inhibitors from natural sources are a good choice for searching for high-efficiency and low-toxicity hypoglycemic drugs. In this study, a naturally effective α-Glu inhibitor aspergillus triazolate A (ATA) with a peculiar structure was first found in Oxalis corniculate L., then its activity and mechanism were first elucidated through various methods. These mechanisms included enzyme kinetics, circular dichroism spectra, fluorescence spectra, synchronous fluorescence spectrum, 3D fluorescence spectrum, and molecular docking. Meanwhile, the ability to reduce postprandial blood glucose was further investigated in vivo. Research results revealed that ATA was a mixed type α-Glu inhibitor with an IC50 value of 66.87 ± 1.50 µM, which bound to the enzyme from a single site through hydrogen bonding and hydrophobic forces causing the looser secondary structure of α-Glu. It was also found that the binding site of α-Glu was closer to the Trp residue, and the endogenous fluorescence of α-Glu was quenched in a static quenching form. Moreover, the sucrose loading test in vivo revealed that the ATA of 20 mg/kg could effectively reduce the postprandial blood glucose level. Hence, ATA could be used as lead compound to develop novel α-Glu inhibitors.

The associations between dietary flavonoids intake and risk of depressive symptom in diabetic patients: Data from NHANES 2007-2008, 2009-2010, and 2017-2018.

BACKGROUND: The increasing incidence of depressive symptoms in diabetic patients contributes to the global burden of disease, but few epidemiological studies have evaluated the relationship between dietary flavonoids intake and depressive symptoms in diabetic patients in American adults. OBJECTIVE: This study intended to evaluate the associations of dietary flavonoids intake and depressive symptoms in diabetic patients in American adults. METHODS: We conducted a cross-sectional analysis of 1993 adults aged ≥20 years old who participated in the 2007-2008, 2009-2010, and 2017-2018 National Health and Nutrition Examination Surveys (NHANES). Chi-square test and independent-sample t-test were used to compare subjects' characteristics. Logistic regression model was further used to analyze the relationship between dietary flavonoid intake and depressive symptoms in diabetic patients. Restricted cubic spline (RCS) analysis was used to investigate the non-linear relationship between dietary flavonoid intake and the prevalence of depressive symptoms in diabetic patients. The weighted quartile sum (WQS) regression was used to analyze the effect of 29 flavonoids monomers. RESULTS: The results showed that the total flavonoid intake in the third quartile (OR, 0.635; 95 % CI,0.419-0.962; P, 0.032) was significantly associated with a reduced risk of depressive symptoms in diabetic patients compared with the lowest quartile. And there was a U-shaped association between dietary flavonoid intake and risk of depressive symptoms in diabetic patients. Top contributors of flavonoid monomers were eriodictyol, naringenin, and theaflavin-3'-gallate, accounting for a percentage of 30.83 %, 22.17 %, and 6.92 %, respectively. CONCLUSION: Moderate (56.07-207.12 mg/day) dietary flavonoid intake was associated with a reduced risk of depressive symptoms in diabetic patients. The important flavonoid monomers were eriodictyol, naringenin, and theaflavin-3'-gallate.

An MRI-Based Radiomics Nomogram for Differentiation of Benign and Malignant Vertebral Compression Fracture.

RATIONALE AND OBJECTIVES: This study aimed to develop and validate a magnetic resonance imaging (MRI)-based radiomics nomogram combining radiomics signatures and clinical factors to differentiate between benign and malignant vertebral compression fractures (VCFs). MATERIALS AND METHODS: A total of 189 patients with benign VCFs (n = 112) or malignant VCFs (n = 77) were divided into training (n = 133) and validation (n = 56) cohorts. Radiomics features were extracted from MRI T1-weighted images and short-TI inversion recovery images to develop the radiomics signature, and the Rad score was constructed using least absolute shrinkage and selection operator regression. Demographic and MRI morphological characteristics were assessed to build a clinical factor model using multivariate logistic regression analysis. A radiomics nomogram was constructed based on the Rad score and independent clinical factors. Finally, the diagnostic performance of the radiomics nomogram, clinical model, and radiomics signature was validated using receiver operating characteristic and decision curve analysis (DCA). RESULTS: Six features were used to build a combined radiomics model (combined-RS). Pedicle or posterior element involvement, paraspinal mass, and fluid sign were identified as the most important morphological factors for building the clinical factor model. The radiomics signature was superior to the clinical model in terms of the area under the curve (AUC), accuracy, and specificity. The radiomics nomogram integrating the combined-RS, pedicle or posterior element involvement, paraspinal mass, and fluid sign achieved favorable predictive efficacy, generating AUCs of 0.92 and 0.90 in the training and validation cohorts, respectively. The DCA indicated good clinical usefulness of the radiomics nomogram. CONCLUSION: The MRI-based radiomics nomogram, combining the radiomics signature and clinical factors, showed favorable predictive efficacy for differentiating benign from malignant VCFs.