Applying dynamic contrast-enhanced MRI tracer kinetic models to differentiate benign and malignant soft tissue tumors.

BACKGROUND: To explore the potential of different quantitative dynamic contrast-enhanced (qDCE)-MRI tracer kinetic (TK) models and qDCE parameters in discriminating benign from malignant soft tissue tumors (STTs). METHODS: This research included 92 patients (41females, 51 males; age range 16-86 years, mean age 51.24 years) with STTs. The qDCE parameters (Ktrans, Kep, Ve, Vp, F, PS, MTT and E) for regions of interest of STTs were estimated by using the following TK models: Tofts (TOFTS), Extended Tofts (EXTOFTS), adiabatic tissue homogeneity (ATH), conventional compartmental (CC), and distributed parameter (DP). We established a comprehensive model combining the morphologic features, time-signal intensity curve shape, and optimal qDCE parameters. The capacities to identify benign and malignant STTs was evaluated using the area under the curve (AUC), degree of accuracy, and the analysis of the decision curve. RESULTS: TOFTS-Ktrans, EXTOFTS-Ktrans, EXTOFTS-Vp, CC-Vp and DP-Vp demonstrated good diagnostic performance among the qDCE parameters. Compared with the other TK models, the DP model has a higher AUC and a greater level of accuracy. The comprehensive model (AUC, 0.936, 0.884-0.988) demonstrated superiority in discriminating benign and malignant STTs, outperforming the qDCE models (AUC, 0.899-0.915) and the traditional imaging model (AUC, 0.802, 0.712-0.891) alone. CONCLUSIONS: Various TK models successfully distinguish benign from malignant STTs. The comprehensive model is a noninvasive approach incorporating morphological imaging aspects and qDCE parameters, and shows significant potential for further development.

zDHHC3-mediated S-palmitoylation of SLC9A2 regulates apoptosis in kidney clear cell carcinoma.

PURPOSE: Kidney clear cell carcinoma (KIRC) has a poor prognosis, high morbidity and mortality rates, and high invasion and metastasis rate, and effective therapeutic targets are lacking. zDHHC3 has been implicated in various cancers, but its specific role in KIRC remains unclear. METHODS: In this study, we performed a pan-cancer analysis, bioinformatics analysis, and cell experiment to detect the role of zDHHC3 in KIRC. RESULTS: zDHHC3 was significantly down-regulated in KIRC, and that its high expression was associated with favorable patient outcomes. We identified 202 hub genes that were most relevant to high zDHHC3 expression and KIRC, and found that they were involved mainly in ion transport and renal cell carcinoma. Among these hub genes, SLC9A2 was identified as a downstream gene of zDHHC3. zDHHC3 suppression led to decreased expression and S-palmitoylation of SLC9A2, which further inhibited the apoptosis of Caki-2 cells. CONCLUSION: Our findings suggest that zDHHC3 plays an important role in KIRC, due partly to its regulation of SLC9A2 S-palmitoylation. The targeting of the zDHHC3-SLC9A2 axis may provide a new option for the clinical treatment of KIRC.

The proportion of tumour stroma predicts response to treatment of immune checkpoint inhibitor in combination with chemotherapy in patients with stage IIIB-IV non-small cell lung cancer.

AIMS: Immunotherapy has brought a new era to cancer treatment, yet we lack dependable predictors for its effectiveness. This study explores the predictive significance of intratumour stroma proportion (iTSP) for treatment success and prognosis in non-small cell lung cancer (NSCLC) patients undergoing treatment with immune check-point inhibitors (ICIs) together with chemotherapy. METHODS AND RESULTS: We retrospectively collected data from patients with unresectable stage IIIB-IV NSCLC who were treated with first-line ICIs and chemotherapy. Each patient received a confirmed pathological diagnosis, and the pathologist evaluated the iTSP on haematoxylin and eosin (H&E)-stained sections of diagnostic tissue slides. Among the 102 H&E-stained biopsy samples, 61 (59.8%) were categorised as stroma-L (less than 50% iTSP), while 41 (40.2%) were classified as stroma-H (more than 50% iTSP). We observed that the stroma-L group exhibited a significantly better objective response rate (ORR) (72.1 versus 51.2%, P = 0.031) and deeper response depth (DpR) (-50.49 ± 28.79% versus -35.83 ± 29.91%, P = 0.015) compared to the stroma-H group. Furthermore, the stroma-L group showed longer median progression-free survival (PFS) (9.6 versus 6.0 months, P = 0.011) and overall survival (OS) (24.0 versus 12.2 months, P = 0.001) compared to the stroma-H group. Multivariate Cox proportional hazards regression analysis indicated that iTSP was a highly significant prognostic factor for both PFS [hazard ratio (HR) = 1.713; P = 0.030] and OS (HR = 2.225; P = 0.003). CONCLUSION: Our findings indicate that a lower iTSP corresponds to improved clinical outcomes and greater DpR in individuals with stage IIIB-IV NSCLC treated with first-line ICIs and chemotherapy. The iTSP could potentially serve as a predictive biomarker for ICIs therapy response.

Orderly Nanodendritic Nickel Substitute for Raney Nickel Catalyst Improving Alkali Water Electrolyzer.

The development of nonprecious metal catalysts to meet the activity-stability balance at industrial-grade large current densities remains a challenge toward practical alkali-water electrolysis. Here, this work develops an orderly nanodendritic nickel (ND-Ni) catalyst that consists of ultrafine nanograins in chain-like conformation, which shows both excellent activity and robust stability for large current density hydrogen evolution reaction (HER) in alkaline media, superior to currently applied Raney nickel (R-Ni) catalyst in commercial alkali-water electrolyzer (AWE). The ND-Ni catalyst featured by a three-dimensional (3D) interconnecting microporous structure endows with high specific surface area and excellent conductivity and hydrophilicity, which together afford superior charge/mass transport favorable to HER kinetics at high current densities. An actual AWE with ND-Ni catalyst demonstrates durable water splitting with 1.0 A cm-2 at 1.71 V under industrial conditions and renders a record-low power consumption of 3.95 kW h Nm-3 with an energy efficiency close to 90%. The hydrogen price per gallon of gasoline equivalent (GGE) is calculated to be ≈$0.95, which is less than the target of $2.0 per GGE by 2026 from the U.S. Department of Energy. The results suggest the feasibility of ND-Ni substitute for R-Ni catalyst in commercial AWE.

AURKA, TOP2A and MELK are the key genes identified by WGCNA for the pathogenesis of lung adenocarcinoma.

The comprehensive analysis of single or multiple microarray datasets is currently available in Gene Expression Omnibus (GEO) databases, with several studies having identified genes strongly associated with the development of lung adenocarcinoma (LUAD). However, the mechanisms of LUAD development remain largely unknown and has not yet been systematically studied; thus, further studies are required in this field. In the present study, weighted gene co-expression network analysis (WGCNA) was used for the evaluation of key genes with potential high risk of LUAD, and to provide more reliable evidence concerning its pathogenesis. The GSE140797 dataset from the high-throughput GEO database was downloaded and was first analyzed using the Limma package in the R language in order to determine the differentially expressed genes. The dataset was then analyzed using the WGCNA package to analyze the co-expressed genes, and the modular genes with the highest correlation with the clinical phenotype were identified. Subsequently, the pathogenic genes shared in common between the result of the two analyses were imported into the STRING database for protein-protein interaction network analysis. The hub genes were screened out using Cytoscape, and then The Cancer Genome Atlas analysis, receiver operating characteristic analysis and survival analysis were subsequently performed. Finally, the key genes were evaluated using reverse transcription-quantitative PCR and western blot analysis. Bioinformatics analysis of the GSE140797 dataset revealed eight key genes: AURKA, BUB1, CCNB1, CDK1, MELK, NUSAP1, TOP2A and PBK. Finally, the AURKA, TOP2A and MELK genes were evaluated in samples from patients with lung cancer using WGCNA and RT-qPCR, western blot analysis experiments, providing basis for further research on the mechanisms of LUAD development and targeted therapy.

Astragalus polysaccharide ameliorated complex factor-induced chronic fatigue syndrome by modulating the gut microbiota and metabolites in mice.

Chronic fatigue syndrome (CFS) is a debilitating disease with no symptomatic treatment. Astragalus polysaccharide (APS), a component derived from the traditional Chinese medicine A. membranaceus, has significant anti-fatigue activity. However, the mechanisms underlying the potential beneficial effects of APS on CFS remain poorly understood. A CFS model of 6-week-old C57BL/6 male mice was established using the multiple-factor method. These mice underwent examinations for behavior, oxidative stress and inflammatory indicators in brain and intestinal tissues, and ileum histomorphology. 16 S rDNA sequencing analysis indicated that APS regulated the abundance of gut microbiota and increased production of short chain fatty acids (SCFAs) and anti-inflammatory bacteria. In addition, APS reversed the abnormal expression of Nrf2, NF-κB, and their downstream factors in the brain-gut axis and alleviated the reduction in SCFAs in the cecal content caused by CFS. Further, APS modulated the changes in serum metabolic pathways induced by CFS. Finally, it was verified that butyrate exerted antioxidant and anti-inflammatory effects in neuronal cells. In conclusion, APS could increase the SCFAs content by regulating the gut microbiota, and SCFAs (especially butyrate) can further regulate the oxidative stress and inflammation in the brain, thus alleviating CFS. This study explored the efficacy and mechanism of APS for CFS from the perspective of gut-brain axis and provides a reference to further explore the efficacy of APS and the role of SCFAs in the central nervous system.

Nobiletin attenuates monocrotaline-induced pulmonary arterial hypertension through PI3K/Akt/STAT3 pathway.

OBJECTIVES: Nobiletin is a flavonoid found in the peel of Citrus sinensis (oranges). The purpose of this study is to investigate whether Nobiletin can alleviate the monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and explore the underlying mechanisms. METHODS: The PAH rat model was replicated by subcutaneous injection of MCT. Nobiletin (1, 5 and 10 mg/kg) was administered by gavage from day 1 to day 21. After 21 days of MCT injection, the mean pulmonary artery pressure, pulmonary vascular resistance, Fulton Index, pulmonary artery remodelling, blood routine parameters, liver and kidney functions was measured. The level of inflammatory cytokines and PI3K/Akt/STAT3 were detected by qPCR, ELISA and western blot, the proliferation of pulmonary artery smooth muscle cells (PASMCs) was evaluated by CCK-8. KEY FINDINGS: Nobiletin (10 mg/kg) inhibited the MCT-induced increase in mean pulmonary artery pressure and pulmonary vascular resistance, right ventricular hypertrophy and pulmonary artery remodelling in rats. Nobiletin decreased the levels of inflammatory cytokines and phosphorylation level of PI3K/Akt/STAT3 in lungs of MCT-treated rats. Nobiletin inhibited the proliferation and lowered the inflammatory cytokines level induced by PDGF-BB in PASMCs. CONCLUSION: Nobiletin attenuates MCT-induced PAH, and the potential mechanism is to inhibit inflammation through PI3K/Akt/STAT3 pathway.

Pitsubcosides A-L, highly esterified eudesmane sesquiterpenoid glycosides with antibacterial activity from Pittosporum subulisepalum and their mechanism.

BACKGROUND: Plants from the genus Pittosporum are traditionally used as antibacterial, antifungal and antiviral agents. A bioassay evaluation of the extract of Pittosporum subulisepalum revealed antibacterial activity. This study focused on the discovery of the antibacterial metabolism in P. subulisepalum, as well as the modes of action of its active components. RESULTS: A chemical investigation of an ethyl acetate (EtOAc) extract of the aerial parts of P. subulisepalum led to the isolation of 12 previously undescribed eudesmane sesquiterpenoid glycoside esters (ESGEs), pitsubcosides A-L (1-12). Their structures were elucidated by extensive spectroscopic analysis, including one- and two-dimensional NMR, high-resolution electrospray ionization mass spectrometry, electronic circular dichroism spectra and single-crystal X-ray crystallography analysis or by comparing with authentic samples. The new ESGEs were characterized by their highly esterified glycoside moieties. Among them, compounds 1-3, 5 and 8 showed a moderate inhibitory effect against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Bacillus cereus, Bacillus subtilis, Pseudomonas syringae pv. actinidiae (Psa) and Erwinia carotovora with minimum inhibitory concentrations (MICs) ranging from 3.13 to 100 µm. Among them, compounds 3 and 5 showed remarkable antibacterial activity against S. aureus and Psa with MIC values of 6.25 and 3.13 µm, respectively. Live bacterial mass and the biofilms of S. aureus and Psa were quantified using methyl tetrazolium and crystal violet assays. Fluorescence microscopy and scanning electron microscopy experiments revealed an antibacterial mechanism of cell membrane architectural disruption. CONCLUSION: The results suggest that ESGEs possess great potential for the development of antibacterial agents to control plant pathogens. © 2023 Society of Chemical Industry.

MiR-133a/CD47 axis is a novel prognostic biomarker to promote triple negative breast cancer progression.

Cluster of differentiation 47 (CD47) acts as an anti-engulfment signal on tumor cells, and its overexpression is correlated with poor prognosis of various malignant tumors. However, the role and mechanism of CD47 in tumor cell proliferation, migration and apoptosis remain unclarified. Emerging evidence indicates that microRNAs (miRNAs) are potential regulators to mediate CD47 generation. In this study, we found that CD47 was up-regulated while miR-133a was down-regulated in triple-negative breast cancer (TNBC) in vitro and in vivo. Moreover, we demonstrated for the first time that CD47 was a direct target of miR-133a in TNBC cells, and provided direct evidence of the inverse correlation between miR-133a and CD47 expression in TNBC. Besides, miR-133a functioned as a tumor suppressor to inhibit proliferation and migration, and promote apoptosis of TNBC cells by targeting CD47. Furthermore, overexpression of miR-133a inhibited the tumor growth of TNBC in an in vivo xenograft animal model by targeting CD47. Thus, miR-133a/CD47 axis provides new insight into the mechanism of TNBC progression and could be a promising candidate in the diagnosis and treatment of TNBC.

Pheophorbide-a as a Light-Triggered Liposomal Switch: For the Controlled Release of Alpinia galanga (A. galanga) Essential Oil and Its Stability, Antioxidant, and Antibacterial Activity Assessment.

In this study, Alpinia galanga essential oil liposomes (EO-Lip) were prepared with soybean lecithin and cholesterol as wall materials. A light-responsive liposome (EO-PLip) was designed for the controlled release of A. galanga oil based on the light-responsive properties of Pheophorbide-a. The dependence of Pheophorbide-a on illumination time was proved by UV spectroscopy. Characterization techniques such as UV spectroscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy demonstrated that the essential oils were successfully encapsulated in liposomes. Moreover, the particle size of EO-PLip was 166.30 nm, the polydispersity index was 0.22, the zeta potential was -49.50 mV, and the encapsulation efficiency was 30.83%. Both EO-Lip and EO-Plip have high sustained-release effects on essential oil and showed light-responsive release characteristics under infrared stimulation. The prepared liposomes had good storage stability at 4 °C for 28 d. EO-PLip showed excellent transient antioxidant and bacteriostatic properties based on the ability to respond to light and slow release. This EO-PLip provided a platform for essential oils and might be used as a potent and controllable solution.

Research progress on near-infrared long persistent phosphor materials in biomedical applications.

After excitation is stopped, long persistent phosphor materials (LPPs) can emit light for a long time. The most important feature is that it allows the separation of excitation and emission in time. Therefore, it plays a vital role in various fields such as data storage, information technology, and biomedicine. Owing to the unique mechanism of storage and luminescence, LPPs can avoid the interference of sample autofluorescence, as well as show strong tissue penetration ability, good afterglow performance, and rich spectral information in the near-infrared (NIR) region, which provides a broad prospect for the application of NIR LPPs in the field of biomedicine. In recent years, the development and applications in biomedical fields have been advanced significantly, such as biological imaging, sensing detection, and surgical guidance. In this review, we focus on the synthesis methods and luminescence mechanisms of different types of NIR LPPs, as well as their applications in bioimaging, biosensing detection, and cancer treatment in the field of biomedicine. Finally, future prospects and challenges of NIR LPPs in biomedical applications are also discussed.

Mechanism of action of CTRP6 in the regulation of tumorigenesis in the digestive system.

Tumors of the digestive system have always received attention, and their occurrence and development are regulated by various mechanisms such as inflammation and immunity, glucose and lipid metabolism, and tumor angiogenesis. Complement Clq/TNF-related protein 6 (CTRP6) is a member of the CTRP family; it is widely expressed in various tissues and cell types, and plays a biological role in a number of mechanisms, such as glucose and lipid metabolism and inflammation. Recent studies have revealed the tumor-promoting effect of CTRP6 in gastric cancer, liver cancer, colorectal cancer and other gastrointestinal tumors, but, to the best of our knowledge, there has been no systematic discussion on the tumor-promoting mechanism of CTRP6. The present study reviews the role of CTRP6 in tumors of the digestive system and its possible mechanisms.

Atomic-scale regulation of anionic and cationic migration in alkali metal batteries.

The regulation of anions and cations at the atomic scale is of great significance in membrane-based separation technologies. Ionic transport regulation techniques could also play a crucial role in developing high-performance alkali metal batteries such as alkali metal-sulfur and alkali metal-selenium batteries, which suffer from the non-uniform transport of alkali metal ions (e.g., Li+ or Na+) and detrimental shuttling effect of polysulfide/polyselenide anions. These drawbacks could cause unfavourable growth of alkali metal depositions at the metal electrode and irreversible consumption of cathode active materials, leading to capacity decay and short cycling life. Herein, we propose the use of a polypropylene separator coated with negatively charged Ti0.87O2 nanosheets with Ti atomic vacancies to tackle these issues. In particular, we demonstrate that the electrostatic interactions between the negatively charged Ti0.87O2 nanosheets and polysulfide/polyselenide anions reduce the shuttling effect. Moreover, the Ti0.87O2-coated separator regulates the migration of alkali ions ensuring a homogeneous ion flux and the Ti vacancies, acting as sub-nanometric pores, promote fast alkali-ion diffusion.

Automated and rapid detection of cancer in suspicious axillary lymph nodes in patients with breast cancer.

Preoperative staging of suspicious axillary lymph nodes (ALNs) allows patients to be triaged to ALN dissection or to sentinel lymph node biopsy (SLNB). Ultrasound-guided fine needle aspiration (FNA) and cytology of ALN is moderately sensitive but its clinical utility relies heavily on the cytologist's experience. We proposed that the 5-h automated GeneXpert system-based prototype breast cancer detection assay (BCDA) that quantitatively measures DNA methylation in ten tumor-specific gene markers could provide a facile, accurate test for detecting cancer in FNA of enlarged lymph nodes. We validated the assay in ALN-FNA samples from a prospective study of patients (N = 230) undergoing SLNB. In a blinded analysis of 218 evaluable LN-FNAs from 108 malignant and 110 benign LNs by histology, BCDA displayed a sensitivity of 90.7% and specificity of 99.1%, achieving an area under the ROC curve, AUC of 0.958 (95% CI: 0.928-0.989; P < 0.0001). Next, we conducted a study of archival FNAs of ipsilateral palpable LNs (malignant, N = 72, benign, N = 53 by cytology) collected in the outpatient setting prior to neoadjuvant chemotherapy (NAC). Using the ROC-threshold determined in the prospective study, compared to cytology, BCDA achieved a sensitivity of 94.4% and a specificity of 92.5% with a ROC-AUC = 0.977 (95% CI: 0.953-1.000; P < 0.0001). Our study shows that the automated assay detects cancer in suspicious lymph nodes with a high level of accuracy within 5 h. This cancer detection assay, scalable for analysis to scores of LN FNAs, could assist in determining eligibility of patients to different treatment regimens.

Spin Transport Properties of One-Dimensional Benzene Ligand Organobimetallic Sandwich Molecular Wires.

Organometallic sandwich complexes, composed of cyclic hydrocarbon ligands and transition-metal atoms, display unique physical and chemical properties. In this work, the electronic and spin transport properties of one-dimensional (1D) VBz2 ligand bimetallic sandwich complexes, VBz2-TM (TM = Cr, Mn, and Fe), are systematically investigated using density functional theory and nonequilibrium Green's function method. The results show that all the 1D infinite molecular wires [(VBz2)TM]∞ (TM = Cr-Fe) are found to be thermodynamically stable with high binding energies (∼1.0-3.45 eV). In particular, they are predicted to be ferromagnetic half metals. Moreover, the I-V curves exhibit negative differential resistance for one, two, and three VBz2-TM wires at TM = Cr, Mn, and Fe, respectively, which is of great significance for certain electronic applications. Our findings strongly suggest that the benzene ligand bimetallic sandwich molecular wires are good candidates for potential electronics and spintronics.

Effect of fluoride on osteocyte-driven osteoclastic differentiation.

Excessive systemic uptake of inorganic fluorides causes disturbances of bone homeostasis. The mechanism of skeletal fluorosis is still uncertain. This study aimed to study the effect of fluoride on osteocyte-driven osteoclastogenesis and probe into the role of PTH in this process. IDG-SW3 cells seeded in collagen-coated constructs were developed into osteocyte-like cells through induction of mineral agents. Then, osteocyte-like cells were exposed to fluoride in the presence or absence of parathyroid hormone (PTH). Cell viability and their capacity to produce receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and sclerostin (SOST) were detected by MTT and Western blot assays, respectively. Finally, a transwell coculture system using osteocyte-like cells seeded in the low compartment, and osteoclast precursors added in the inserts was developed to observe the osteocyte-driven osteoclasogenesis response to fluoride with or without PTH, and the expression of molecules involved in this mechanism were measure by real time RT-PCR. Results showed that osteocytes withstood a toxic dose of fluoride, and yet PTH administration significantly reduced osteocytes viability. PTH amplified the effect of fluoride on the expression of osteoclastogenesis-related molecules in osteocyte, but did not enlarged the stimulating effect of fluoride on osteoclastogenesis drove by osteocyte coculture. Gene expression levels of TRAP, RANK, JNK and NFAtc1 significantly increased in fluoride affected osteoclast precursor cocultured with osteocyte-like cells. The impact of fluoride on osteocyte-driven osteoclast differentiation was stronger than that of PTH. In conclusion, osteocyte played a pivotal role on the mechanism underlying fluoride-affected osteoclastogenesis in which RANK-JNK-NFATc1 signaling pathway was involved, and PTH had a significant impact in this process.

A LiPO2F2/LiPF6 dual-salt electrolyte enabled stable cycling performance of nickel-rich lithium ion batteries.

In this work, a dual-lithium salt was proposed for constructing an electrolyte for high energy density lithium ion batteries. LiPO2F2 was composed with traditional LiPF6 to enhance the high voltage performance of the electrolyte. The electrochemical performance of the NCM811/Li cells with LiPO2F2/LiPF6 dual-lithium salt at 2.8-4.5 V was investigated. It was found that the dual-lithium salt can inhibit the oxidative decomposition of the electrolyte, suppress the dissolution of the transition metal ions in the electrode material, and reduce the side reaction between the transition metal ions and the electrolyte. We believe that the strategy of a dual-lithium salt electrolyte may provide a new idea to stabilize the electrode/electrolyte interface at high voltage, which is very important for developing high energy density batteries.

Different Effects of Fluoride Exposure on the Three Major Bone Cell Types.

Fluoride accumulates and is toxic to bones. Clinical bone lesions occur in a phased manner, being less severe early in the natural course of skeletal fluorosis. Previous research rarely focused on osteocyte, osteoclast, and osteoblast at the same time, although these three types of cells are involved in the process of fluorosis. In this study, commitment of bone cells was performed according to their respective characteristics. Osteocyte-like cells were verified by protein expression of sclerostin (SOST) in IDG-SW3 cell culture with mineral medium. Positive tartrate-resistant acid phosphatase (TRACP) staining, characteristic of osteoclasts, is observed in RAW264.7 cells after administration of RANKL. We successfully purified a high percentage (94%) of bone mesenchymal stem cells (BMSCs) co-expressing CD34 and CD44. Parallel studies were performed to observe cell viability and apoptosis rates in osteocyte, osteoclast, and osteoblast like cells by using MTT and Annexin V FITC assays. Our results demonstrated that osteocytes have a strong tolerance to high fluoride concentrations, while osteoclasts are more sensitive to changes of fluoride dose. The range of anabolic action of fluoride concentration on osteoblast was narrow. Notably, fluoride exposure aggravated apoptosis of osteocyte and osteoclast induced by administration of PTH and TGF-ß, respectively. In short, three types of bone cells display disparate responses to fluoride exposure and to PTH- and TGF-ß-induced apoptosis.

Association of soft tissue infection in the extremity with glucose and lipid metabolism and inflammatory factors.

Association of soft tissue infection in the extremity with glucose and lipid metabolism as well as inflammatory factors was investigated. One hundred and twenty-six patients with diabetes mellitus (DM) complicated with soft tissue infection in the lower extremity admitted and treated in Dongying People's Hospital from March 2016 to February 2017 were selected and divided into mild (n=46), moderate (n=43) and severe group (n=37) according to the severity of the soft tissue infection in the lower extremity. The glucose and lipid metabolism, inflammatory factors and influencing factors were compared among different groups of patients before treatment, and the changes in glucose and lipid metabolism as well as inflammatory factors were observed after treatment. Before treatment, the levels of free fatty acid (FFA), fasting plasma glucose (FPG), fasting insulin (FINS), vascular cell adhesion molecule-1 (VCAM-1), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in mild group were remarkably lower than those in moderate and severe groups, while the serum adiponectin (APN) level was obviously higher (P<0.05). Logistic regression analysis indicated that FFA, FPG, FINS, APN, VCAM-1, CRP, TNF-α and IL-6 were risk factors influencing soft tissue infection in the extremity (P<0.05). After treatment, among the 126 patients, the levels of FFA, FPG, FINS, VCAM-1, CRP, TNF-α and IL-6 were decreased markedly, while the APN level was increased evidently (P<0.05). Compared with patients innon-toe/extremity amputation group, patients in toe/extremity amputation group had elevated levels of FFA, FPG, FINS, VCAM-1, CRP, TNF-α and IL-6 as well as declined APN level (P<0.05). Glucose and lipid metabolism and inflammatory factors are closely related to soft tissue infection in the extremity.

An overview of grayanane diterpenoids and their biological activities from the Ericaceae family in the last seven years.

Grayanane diterpenoids, possessing a unique 5/7/6/5 tetracyclic system, exist exclusively in plants of the Ericaceae family. Owing to their various skeletons, complex structures, and diverse bioactivities, grayanoids have been the topic of research in many phytochemical and pharmacological laboratories, offering opportunities for the development of new drugs with analgesic, anti-inflammatory, and protein tyrosine phosphatase 1B (PTP1B) properties. Recently, a number of new grayanane diterpenoids with unprecedented carbon skeletons have been obtained from plants of the Ericaceae family, and they exhibit diverse biological properties, such as agalgesic, antinociceptive, anticancer, antiviral, antifeedant, insecticidal, toxicity, and PTP1B. In this review, 162 new grayanoids with 14 carbon skeletons from the Ericaceae family over the past seven years (2012-October 2018) are discussed, including their occurrence and distribution, skeleton types, structural features, biological activities, and structure-activity relationships (SARs). Also, strategies for the structural elucidation are summarized to provide useful information for medicinal chemists in developing potent anticancer, antiviral, analgesic, anti-inflammatory, and novel PTP1B agents.