Discovery of an immunosuppressive functional metabolite from the insect-derived endophytic Aspergillus taichungensis SMU01.

Three p-terphenyl metabolites (1-3), three indole-diterpenoids (4-6), an herbicide sesquiterpene (7), a flavonoid (8), and five other small molecules containing nitrogen (9-13) were isolated from the medicinal insect (Periplaneta americana)-derived endophytic Aspergillus taichungensis SMU01. Their chemical structures were elucidated on the basis of spectroscopic data and quantum chemical computational methods. Biological activity of these isolates in the differentiation of mouse CD4+ T cell subsets was evaluated. Importantly, metabolites 2 targeting JAK-STAT signaling pathway could hold potential benefits in maintaining peripheral immune homeostasis and alleviating the progression of autoimmune diseases.

Identification and validation of immune and prognosis-related genes in hepatocellular carcinoma: A review.

PURPOSE: Bioinformatics methods were used to identify the key genes associated with the immune microenvironment of hepatocellular carcinoma (HCC) to construct an immune risk prognostic model (IRPM) and to study the correlation between IRPM's risk groups and immune characteristics of patients with HCC. METHODS: HCC transcriptome sequencing information was searched for immune-related genes (IRGs) that were regularly expressed in cancer tissues. The IRGs, which were strongly linked to overall survival were screened; the prognostic characteristics model was constructed using Cox regression analysis. IRPM's independent prognostic value was explored; Kaplan-Meier survival and receiver-operating characteristic curves were used to determine the model prediction ability in the led-to queue. RESULTS: Patients in the high-risk group (HRG) showed significantly poor outcomes. Gene Set Enrichment Analysis revealed factors involved in both the HRG and low risk group. Immune-related hub genes (IRHGs) and drug sensitivity expression levels revealed that all IRHGs were correlated with drug sensitivity for certain chemotherapy drugs. CONCLUSION: The study results may serve as a reference for improving prognosis, early screening, and immunotherapy in patients with HCC.

Development and Validation of an Artificial Intelligence Model for Small Bowel Capsule Endoscopy Video Review.

Importance: Reading small bowel capsule endoscopy (SBCE) videos is a tedious task for clinicians, and a new method should be applied to solve the situation. Objectives: To develop and evaluate the performance of a convolutional neural network algorithm for SBCE video review in real-life clinical care. Design, Setting, and Participants: In this multicenter, retrospective diagnostic study, a deep learning neural network (SmartScan) was trained and validated for the SBCE video review. A total of 2927 SBCE examinations from 29 medical centers were used to train SmartScan to detect 17 types of CE structured terminology (CEST) findings from January 1, 2019, to June 30, 2020. SmartScan was later validated with conventional reading (CR) and SmartScan-assisted reading (SSAR) in 2898 SBCE examinations collected from 22 medical centers. Data analysis was performed from January 25 to December 31, 2021. Exposure: An artificial intelligence-based tool for interpreting clinical images of SBCE. Main Outcomes and Measures: The detection rate and efficiency of CEST findings detected by SSAR and CR were compared. Results: A total of 5825 SBCE examinations were retrospectively collected; 2898 examinations (1765 male participants [60.9%]; mean [SD] age, 49.8 [15.5] years) were included in the validation phase. From a total of 6084 CEST-classified SB findings, SSAR detected 5834 findings (95.9%; 95% CI, 95.4%-96.4%), significantly higher than CR, which detected 4630 findings (76.1%; 95% CI, 75.0%-77.2%). SmartScan-assisted reading achieved a higher per-patient detection rate (79.3% [2298 of 2898]) for CEST findings compared with CR (70.7% [2048 of 2298]; 95% CI, 69.0%-72.3%). With SSAR, the mean (SD) number of images (per SBCE video) requiring review was reduced to 779.2 (337.2) compared with 27 910.8 (12 882.9) with CR, for a mean (SD) reduction rate of 96.1% (4.3%). The mean (SD) reading time with SSAR was shortened to 5.4 (1.5) minutes compared with CR (51.4 [11.6] minutes), for a mean (SD) reduction rate of 89.3% (3.1%). Conclusions and Relevance: This study suggests that a convolutional neural network-based algorithm is associated with an increased detection rate of SBCE findings and reduced SBCE video reading time.

Combined Acupoints for the Treatment of Patients with Obesity: An Association Rule Analysis.

Obesity is a prevalent metabolic disease that increases the risk of other diseases, such as hypertension, diabetes, hyperlipidemia, cardiovascular disease, and certain cancers. A meta-analysis of 11 randomized sham-controlled trials indicates that acupuncture had adjuvant benefits in improving simple obesity, and previous studies have reported that acupoint combinations were more useful than single-acupoint therapy. The Apriori algorithm, a data mining-based analysis that finds potential correlations in datasets, is broadly applied in medicine and business. This study, based on the Apriori algorithm-based association rule analysis, found the association rules of acupoints among 11 randomized controlled trials (RCTs). There were 23 acupoints extracted from 11 RCTs. We used Python to calculate the association between acupoints and disease. We found the top 10 frequency acupoints were Extra12, TF4, LI4, LI11, ST25, ST36, ST44, CO4, CO18, and CO1. We investigated the 1118 association rule and found that {LI4, ST36} ≥ {ST44}, {LI4, ST44} ≥ {ST36}, and {ST36, ST44} ≥ {LI4} were the most associated rules in the data. Acupoints, including LI4, ST36, and ST44, are the core acupoint combinations in the treatment of simple obesity.

ßPS-Integrin acts downstream of Innexin 2 in modulating stretched cell morphogenesis in the Drosophila ovary.

During oogenesis, a group of specialized follicle cells, known as stretched cells (StCs), flatten drastically from cuboidal to squamous shape. While morphogenesis of epithelia is critical for organogenesis, genes and signaling pathways involved in this process remain to be revealed. In addition to formation of gap junctions for intercellular exchange of small molecules, gap junction proteins form channels or act as adaptor proteins to regulate various cellular behaviors. In invertebrates, gap junction proteins are Innexins. Knockdown of Innexin 2 but not other Innexins expressed in follicle cells attenuates StC morphogenesis. Interestingly, blocking of gap junctions with an inhibitor carbenoxolone does not affect StC morphogenesis, suggesting that Innexin 2 might control StCs flattening in a gap-junction-independent manner. An excessive level of ßPS-Integrin encoded by myospheroid is detected in Innexin 2 mutant cells specifically during StC morphogenesis. Simultaneous knockdown of Innexin 2 and myospheroid partially rescues the morphogenetic defect resulted from Innexin 2 knockdown. Furthermore, reduction of ßPS-Integrin is sufficient to induce early StCs flattening. Taken together, our data suggest that ßPS-Integrin acts downstream of Innexin 2 in modulating StCs morphogenesis.

Fabrication and Physical Properties of Single-Crystalline Βeta-FeSi2 Nanowires.

In this study, self-catalyzed ß-FeSi2 nanowires, having been wanted but seldom achieved in a furnace, were synthesized via chemical vapor deposition method where the fabrication of ß-FeSi2 nanowires occurred on Si (100) substrates through the decomposition of the single-source precursor of anhydrous FeCl3 powders at 750-950 °C. We carefully varied temperatures, duration time, and the flow rates of carrier gases to control and investigate the growth of the nanowires. The morphology of the ß-FeSi2 nanowires was observed with scanning electron microscopy (SEM), while the structure of them was analyzed with X-ray diffraction (XRD) and transmission electron microscopy (TEM). The growth mechanism has been proposed and the physical properties of the iron disilicide nanowires were measured as well. In terms of the magnetization of ß-FeSi2, nanowires were found to be different from bulk and thin film; additionally, longer ß-FeSi2 nanowires possessed better magnetic properties, showing the room-temperature ferromagnetic behavior. Field emission measurements demonstrate that ß-FeSi2 nanowires can be applied in field emitters.

Synthesis of High-Density Indium Oxide Nanowires with Low Electrical Resistivity.

In this study, indium oxide nanowires of high-density were synthesized by chemical vapor deposition (CVD) through a vapor-liquid-solid (VLS) mechanism without carrier gas. The indium oxide nanowires possess great morphology with an aspect ratio of over 400 and an average diameter of 50 nm; the length of the nanowires could be over 30 µm, confirmed by field-emission scanning electron microscopy (SEM). Characterization was conducted with X-ray diffraction (XRD), transmission electron microscopy (TEM), photoluminescence spectrum (PL). High-resolution TEM studies confirm that the grown nanowires were single crystalline c-In2O3 nanowires of body-centered cubic structures. The room temperature PL spectrum shows a strong peak around 2.22 eV, originating from the defects in the crystal structure. The electrical resistivity of a single indium oxide nanowire was measured to be 1.0 × 10-4 Ω⋅cm, relatively low as compared with previous works, which may result from the abundant oxygen vacancies in the nanowires, acting as unintentional doping.

Single Crystalline Iron Silicide and Beta-Iron Disilicide Nanowires Formed through Chemical Vapor Deposition.

In this paper, we report the synthesis of iron silicide and ß-iron disilicide nanowires with chemical vapor deposition; remarkably, the latter has drawn much attention but has seldom been achieved. We also propose the formation mechanisms for the two phases. To investigate the effects of the growth parameters on compositions and morphologies of the iron silicide nanowires, we changed and studied the reaction time, substrate temperature, position of samples, and pressure. The reaction concentration was found to be altered by all of the parameters; thus, we observed different nanowires in terms of morphologies and compositions with scanning electron microscopy. To confirm the growth direction and crystal structure of the nanowires, we conducted x-ray diffraction and high-resolution transmission electron microscopy studies. With the potential of being utilized as circuit elements in electronic devices for Schottky barriers, ohmic contacts, and interconnection among silicon-based transistors, the silicide work at nanoscale is beneficial for nanoelectronics. Understanding the effects of these growth parameters facilitates the control of nanowire growth with better quality.

Prognostic Impact of Fasting Plasma Glucose on Mortality and Re-Hospitalization in Patients with Acute Heart Failure.

BACKGROUND: The impact of fasting plasma glucose (FPG) on survival outcomes in patients with acute heart failure (HF) is unclear, and the relationship between intensity of glycemic control of FPG in diabetes mellitus (DM) patients and HF prognosis remains uncertain. This retrospective study aimed to evaluate the prognostic impact of FPG in patients with acute HF. METHODS: A total of 624 patients hospitalized with acute HF from October 2000 to April 2014 were enrolled in this study. All patients were stratified by three groups according to their admission FPG levels (i.e., DM, impaired fasting glucose [IFG], and non-DM). All-cause and cardiovascular mortality was the primary end point, and HF re-hospitalization was the secondary end point during follow-up period. RESULTS: A total of 587 patients were included in final analysis. The all-cause mortality rates of patients with DM, IFG, and non-DM were 55.5%, 40.3%, and 39.2%, with significant difference (P = 0.001). Moreover, compared with those with IFG (34.3%) and non-DM (32.6%), patients with DM had significantly higher rate of cardiovascular mortality (45.1%). Multiple Cox regression analysis showed that DM as well as IFG was related to all-cause mortality (DM: hazard ratio [HR] = 1.936, P < 0.001; IFG: HR = 1.672, P = 0.019) and cardiovascular mortality (DM: HR = 1.739, P < 0.001; IFG: HR = 1.817, P = 0.013). However, they were both unrelated to HF re-hospitalization. DM patients with strictly controlled blood glucose (FPG <3.9 mmol/L) had higher all-cause mortality than patients with non-DM, IFG, and DM patients with moderately controlled glucose (3.9 mmol/L≤ FPG <7.0 mmol/L). Likewise, both the primary end point and secondary end point were found to be worse in DM patients with poorly controlled blood glucose (FPG ≥7.0 mmol/L). CONCLUSIONS: IFG and DM were associated with higher all-cause mortality and cardiovascular mortality in patients with acute HF. The association between mortality and admission FPG in DM patients with acute HF appeared U-shaped.

Diverse Coordinative Zinc Complexes Containing Amido-Pyridinate Ligands: Structural and Catalytic Studies.

In this work, zinc complexes containing amidopyridinate ligands substituted with different pendant arms have been described. Treatment of ligand precursors with ZnEt2 at a 1:1 ratio in THF yields zinc ethyl complexes (PyN C 1 Py )2(ZnEt)2 (1) and (PyN C 2 NMe 2 )2(ZnEt)2 (2), respectively. Complexes 1 and 2 show the same geometry as a distorted tetrahedron, but adopt different coordination behaviors supported by the ligands. Complex 1 represents a rare and a non-centrosymmetric mode, which the amido group bridges two zinc centers to form a six-membered ring. However, complex 2 shows a centrosymmetric mode, which the pyridine group links to the zinc centers to form an eight-membered ring. Recrystallization of complex 2 gives an additional complex (PyN C 2 NMe 2 )4Zn3(µ3-O) (3). We attempted to prepare zinc benzyl oxide complexes but afforded only a self-assembly cubane complex Zn7Et6(OBn)8 (4). All molecular structures 1-4 are characterized depending on both single-crystal X-ray and spectroscopic data. Furthermore, their catalytic properties toward the ring opening polymerization of ε-caprolactone and L-lactide, using benzyl alcohol as the initiation reagent, are under investigation.

A Low-Normal Free Triiodothyronine Level Is Associated with Adverse Prognosis in Euthyroid Patients with Heart Failure Receiving Cardiac Resynchronization Therapy.

Thyroid dysfunction is prevalent in patients with heart failure (HF) and hypothyroidism is related to the adverse prognosis of HF subjects receiving cardiac resynchronization therapy (CRT). We aim to investigate whether low-normal free triiodothyronine (fT3) level is related to CRT response and the prognosis of euthyroid patients with HF after CRT implantation.One hundred and thirteen euthyroid patients who received CRT therapy without previous thyroid disease and any treatment affecting thyroid hormones were enrolled. All of patients were evaluated for cardiac function and thyroid hormones (serum levels of fT3, free thyroxine [fT4] and thyroid-stimulating hormone [TSH]). The end points were overall mortality and hospitalization for HF worsening. During a follow-up period of 39 ± 3 weeks, 36 patients (31.9%) died and 45 patients (39.8%) had hospitalization for HF exacerbation. A higher rate of NYHA III/IV class and a lower fT3 level were both observed in death group and HF event group. Multivariate Cox regression analyses disclosed that a lower-normal fT3 level (HR = 0.648, P = 0.009) and CRT response (HR = 0.441, P = 0.001) were both independent predictors of overall mortality. In addition, they were also both related to HF re-hospitalization event (P < 0.01 for both). Patients with fT3 < 3.00 pmol/L had a significantly higher overall mortality than those with fT3 ≥ 3.00 pmol/L (P = 0.027). Meanwhile, a higher HF hospitalization event rate was also found in patients with fT3 < 3.00 pmol/L (P < 0.001).A lower-normal fT3 level is correlated with a worse cardiac function an adverse prognosis in euthyroid patients with HF after CRT implantation.

Effect of Metabolic Syndrome on Risk Stratification for Left Atrial or Left Atrial Appendage Thrombus Formation in Patients with Nonvalvular Atrial Fibrillation.

BACKGROUND: Metabolic syndrome (MS) is a risk factor for stroke and thromboembolism event. Left atrial or LA appendage (LA/LAA) thrombus is a surrogate of potential stroke. The relationship between MS and atrial thrombus remains unclear. In this study, we sought to investigate the effect of MS on risk stratification of LA/LAA thrombus formation in patients with nonvalvular atrial fibrillation (NVAF). METHODS: This cross-sectional study enrolled 294 consecutive NVAF patients without prior anticoagulant and lipid-lowering therapies. LA/LAA thrombus was determined by transesophageal echocardiography. Risk assessment of LA/LAA thrombus was performed using the CHADS2 , CHA2DS2 -VASc, MS, CHADS2 -MS, and CHA2DS2 -VASc-MS scores. Logistic regression analyses were performed to determine which factors were significantly related to LA/LAA thrombus. Odds ratio (OR) including 95% confidence interval was also calculated. The predictive powers of different scores for the risk of LA/LAA thrombus were represented by C-statistics and compared by receiver operating characteristic (ROC) analysis. RESULTS: LA/LAA thrombi were identified in 56 patients (19.0%). Logistic analysis showed that MS was the strongest risk factor for LA/LAA thrombus in NVAF patients (OR = 14.698, P < 0.001). ROC curve analyses revealed that the C-statistics of CHADS2 -MS and CHA2DS2 -VASc-MS was significantly higher than those of CHADS2 and CHA2DS2 -VASc scores (CHADS2 -MS vs. CHADS2 , 0.807 vs. 0.726, P = 0.0019). Furthermore, MS was helpful for identifying individuals with a high risk of LA/LAA thrombus in the population with a low risk of stroke (CHADS2 or CHA2DS2 -VASc score = 0). CONCLUSIONS: MS is associated with LA/LAA thrombus risk in patients with NVAF. In addition to the CHADS2 and CHA2DS2 -VASc scores, the CHADS2 -MS and CHA2DS2 -VASc-MS scores provide additional information on stroke risk assessment.

Role of Circulating Fibrocytes in Cardiac Fibrosis.

OBJECTIVE: It is revealed that circulating fibrocytes are elevated in patients/animals with cardiac fibrosis, and this review aims to provide an introduction to circulating fibrocytes and their role in cardiac fibrosis. DATA SOURCES: This review is based on the data from 1994 to present obtained from PubMed. The search terms were "circulating fibrocytes " and "cardiac fibrosis ". STUDY SELECTION: Articles and critical reviews, which are related to circulating fibrocytes and cardiac fibrosis, were selected. RESULTS: Circulating fibrocytes, which are derived from hematopoietic stem cells, represent a subset of peripheral blood mononuclear cells exhibiting mixed morphological and molecular characteristics of hematopoietic and mesenchymal cells (CD34+/CD45+/collagen I+). They can produce extracellular matrix and many cytokines. It is shown that circulating fibrocytes participate in many fibrotic diseases, including cardiac fibrosis. Evidence accumulated in recent years shows that aging individuals and patients with hypertension, heart failure, coronary heart disease, and atrial fibrillation have more circulating fibrocytes in peripheral blood and/or heart tissue, and this elevation of circulating fibrocytes is correlated with the degree of fibrosis in the hearts. CONCLUSIONS: Circulating fibrocytes are effector cells in cardiac fibrosis.

Interleukin 18 and extracellular matrix metalloproteinase inducer cross-regulation: implications in acute myocardial infarction.

Circulating interleukin-18 (IL-18) is thought to promote atherosclerosis and cardiovascular complications such as plaque rupture. Atherosclerosis is also characterized by smooth muscle cell migration, a consequence of extracellular matrix (ECM) degradation regulated by metalloproteinases (MMPs). Because extracellular matrix metalloproteinase inducer (EMMPRIN) has been shown to promote plaque instability by inducing ECM degradation and MMP synthesis, we investigated whether a cross-regulatory interaction exists between IL-18 and EMMPRIN in human monocytes. EMMPRIN levels in monocytes were markedly greater in 20 patients with acute myocardial infarction (AMI) compared with 20 patients with stable angina pectoris or 20 healthy volunteers (control group). The levels of IL-18 and MMP-9 in serum were also significantly greater in the AMI group in comparison with the other 2 groups. IL-18 levels positively correlated with increased levels of EMMPRIN in monocytes. In vitro, the expression of EMMPRIN was increased in monocytes cultured with IL-18, and IL-18 secretion was augmented in monocytes cultured with EMMPRIN. Gene silencing of EMMPRIN by small interfering RNA reduced monocyte secretion of both IL-18 and MMP-9. In the present study, cross-regulation between IL-18 and EMMPRIN in monocytes was demonstrated. This interaction may amplify the inflammatory cascade and be responsible for increased monocytic MMP-9 serum levels in atherosclerosis, contributing to atherosclerotic plaque destabilization and subsequent AMI.

Optimal strategy of coronary revascularization in chronic kidney disease patients: a meta-analysis.

BACKGROUND: Patients with chronic kidney disease (CKD) have high risks of coronary artery disease (CAD). Coronary revascularization is beneficial for long-term survival, but the optimal strategy remains still controversial. METHODS: We searched studies that have compared percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) for revascularization of the coronary arteries in CKD patients. Short-term (30 days or in-hospital) mortality, long-term (at least 12 months) all-cause mortality, cardiac mortality and the incidence of late myocardial infarction and recurrence of revascularization were estimated. RESULTS: 28 studies with 38,740 patients were included. All were retrospective studies from 1977 to 2012. Meta-analysis showed that PCI group had lower short-term mortality (OR 0.55, 95% CI 0.41 to 0.73, P<0.01), but had higher long-term all-cause mortality (OR 1.29, 95% CI 1.23 to 1.35, P<0.01). Higher cardiac mortality (OR 1.08, 95% CI 1.01 to 1.15, P<0.05), higher incidence of late myocardial infarction (OR 1.78, 95% CI 1.65 to 1.91, P<0.01) and recurring revascularization rate (OR 2.94, 95%CI 2.15 to 4.01, P<0.01) is found amongst PCI treated patients compared to CABG group. CONCLUSIONS: CKD patients with CAD received CABG had higher risk of short-term mortality but lower risks of long-term all-cause mortality, cardiac mortality and late myocardial infarction compared to PCI. This could be due to less probable repeated revascularization.

[Effect of RNAi-mediated silencing of SREBP2 gene on inflammatory cytokine-induced cholesterol accumulation in HepG2 cells].

OBJECTIVE: To investigate the effect of RNA interference (RNAi)-mediated silencing of the SREBP2 on inflammatory cytokine-induced cholesterol accumulation in HepG2 cells. METHODS: Short-hairpin (sh)RNA targeting SREBP2 or negative control (NC) shRNA were transfected into HepG2 cells by a liposomal method. G418-selective culturing was used to obtain the SREBP2 shRNA HepG2 and NC shRNA HepG2 cell lines. The two cell lines were cultured in serum-free medium and left untreated (control) or treated with TNF-a (20 ng/ml), low-density lipoprotein (LDL) loading (100 mug/ml), or a combination LDL plus TNF-a treatment. Lipid accumulation was evaluated by oil red O (ORO) staining. Intracellular cholesterol level was measured by enzymatic assay. The mRNA and protein levels of SREBP2 and its downstream target genes, LDL receptor (LDLr), and HMGCoA reductase, were measured by real-time PCR and Western blotting, respectively. RESULTS: SREBP2 shRNA HepG2 and NC shRNA HepG2 stable cell lines were successfully established. ORO staining and cholesterol quantitative analysis showed that LDL loading significantly increased intracellular cholesterol and that expression of SREBP2 further exacerbated the inflammatory cytokine-induced lipid accumulation, as seen in NC shRNA HepG2 cells. LDL loading of NC shRNA HepG2 decreased the gene and protein expressions of SREBP2, LDLr, and HMGCoA reductase, but the suppressive effect was overridden by inflammatory cytokine. SREBP2 shRNA HepG2 cells showed lower levels of cholesterol accumulation under LDL loading and inflammatory stress conditions. Moreover, the mRNA and protein levels of SREBP2, LDLr, and HMGCoA reductase were much lower than in NC shRNA HepG2 cells under the same conditions. CONCLUSION: Inflammatory cytokine exacerbated cholesterol accumulation in HepG2 via disrupting SREBP2. RNAi-mediated inhibition of SREBP2 expression significantly ameliorated the cholesterol accumulation induced by inflammatory cytokine.

Perinatal androgenization prevents age-related neuron loss in the sexually dimorphic nucleus of the preoptic area in female rats.

To investigate the effect of perinatal testosterone exposure, which simulates the endogenous testosterone peak, on neuron loss during aging, nuclear morphology was evaluated in male and female rats as well as in female rats treated with testosterone perinatally followed by ovariectomy (TE/Ovx). Additionally, neuronal apoptosis, which occurred primarily at postnatal day 8 (PND8), was identified by in situ TUNEL staining. Neuronal density, nuclear volume, total neuronal number and pyknotic ratio were estimated after HE stain at PND8, middle age and old age. The results showed that age-related decrease in neuronal nuclear volume and total neuron number in the sexually dimorphic nucleus of the preoptic area (SDN-POA) of female rats was significantly diminished by TE/Ovx. The pyknotic ratio in the SDN-POA of female rats at PND8 was significantly higher than that of males, and neuronal death was reversed by testosterone exposure, while no significant difference of pyknotic ratios was observed among male, female and TE/Ovx female rats at both middle and old age. Moreover, the high apoptotic incidence of female rats at PND8 was significantly diminished by testosterone exposure. These results suggest that neuron loss in the SDN-POA during aging may be predominantly determined by perinatal testosterone through modulation of postnatal neuronal apoptosis.