Circulating microRNA-33b levels are associated with the presence and severity of coronary heart disease.

MicroRNA-33b (miR-33b) affected various biological pathways in regulating cholesterol homeostasis which may link to the pathogenesis of atherosclerotic lesions. However, whether this marker is associated with the presence and severity of coronary heart disease (CHD) is undetermined. We aim to explore the diagnostic value of circulating miR-33b level in the presence and severity of CHD. Altogether 320 patients were enrolled, including 240 patients diagnosed with CHD while 80 were classified as controls after CAG examination. Circulating miR-33b level was analyzed in all subjects, the Gensini score was calculated to assess the severity of stenotic lesions. The association between miR-33b and the presence and severity of CHD was analyzed, and the diagnostic potential of miR-33b of CHD was performed by the receiver operating characteristic (ROC) analysis. The CHD group had higher miR-33b levels (p < 0.001), and the miR-33b content significantly elevated following an increasing Gensini score (p for trend < 0.001). After adjustments for potential risk factors, such as several blood lipid markers, miR-33b remained a significant determinant for CHD (p < 0.001). ROC analysis disclosed that the AUC was 0.931. The optimal cutoff value of miR-33b was with a sensitivity of 81.3% and a specificity of 98.7% in differentiating CHD. It can prognosticate that the higher level of miR-33b was linked to increased severity of disease in CHD patients. Thus, the application of this marker might assist in the diagnosis and classification of CHD patients. Nevertheless, additional studies with larger sample sizes will be required to verify these results.

High Engraftment and Metastatic Rates in Orthotopic Xenograft Models of Gastric Cancer via Direct Implantation of Tumor Cell Suspensions.

Although the implantation of intact tumor fragments is a common practice to generate orthotopic xenografts to study tumor invasion and metastasis, the direct implantation of tumor cell suspensions is necessary when prior manipulations of tumor cells are required. However, the establishment of orthotopic xenografts using tumor cell suspensions is not mature, and a comparative study directly comparing their engraftment and metastatic capabilities is lacking. It is unclear whether tumor fragments are superior to cell suspensions for successful engraftment and metastasis. In this study, we employed three GC cell lines with varying metastatic capacities to stably express firefly luciferase for monitoring tumor progression in real time. We successfully minimized the risk of cell leakage during the orthotopic injection of tumor cell suspensions without Corning Matrigel by systematically optimizing the surgical procedure, injection volume, and needle size options. Comparable high engraftment and metastatic rates between these two methods were demonstrated using MKN-45 cells with a strong metastatic ability. Importantly, our approach can adjust the rate of tumor progression flexibly and cuts the experimental timeline from 10-12 weeks (for tumor fragments) to 4-5 weeks. Collectively, we provided a highly reproducible procedure with a shortened experimental timeline and low cost for establishing orthotopic GC xenografts via the direct implantation of tumor cell suspensions.

Aberrant Spontaneous Brain Activity and its Association with Cognitive Function in Non-Obese Nonalcoholic Fatty Liver Disease: A Resting-State fMRI Study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has been proven to be associated with an increased risk of cognitive impairment and dementia, and this association is more significant in non-obese NAFLD populations, but its pathogenesis remains unclear. Our study aimed to explore the abnormalities of spontaneous brain activity in non-obese NAFLD patients by resting-state fMRI (RS-fMRI) and their relationship with cognitive function. METHODS: 19 non-obese NAFLD, 25 obese NAFLD patients, and 20 healthy controls (HC) were enrolled. All subjects underwent RS-fMRI scan, psychological scale assessment, and biochemical examination. After RS-fMRI data were preprocessed, differences in low-frequency fluctuation amplitude (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were compared among the three groups. Furthermore, the relationship between RS-fMRI indicators and cognitive and clinical indicators were performed using correlation analysis. RESULTS: The cognitive function was declined in both NAFLD groups. Compared with obese NAFLD patients, non-obese NAFLD patients showed increased ALFF and ReHo in the left middle temporal gyrus (MTG), increased ReHo in the sensorimotor cortex and reduced FC between left MTG and right inferior frontal gyrus (IFG). Compared with HC, non-obese NAFLD patients showed increased ALFF and ReHo in the left calcarine cortex and fusiform gyrus (FG), decreased ALFF in the bilateral cerebellum, and reduced FC between left FG and right IFG and left angular gyrus. In addition to the same results, obese patients showed increased activity in different regions of the bilateral cerebellum, while decreased ALFF in the right superior frontal gyrus and ReHo in the right orbitofrontal cortex (OFC). Correlation analysis showed that in non-obese patients, the ALFF values in the FG and the FC values between the left MTG and the right IFG were associated with cognitive decline, insulin resistance, and fasting glucose disorder. CONCLUSIONS: Non-obese NAFLD patients showed abnormal local spontaneous activity and FC in regions involved in the sensorimotor, temporo-occipital cortex, cerebellum, and reward system (such as OFC), some of which may be the potential neural mechanism difference from obese NAFLD patients. In addition, the temporo-occipital cortex may be a vulnerable target for cognitive decline in non-obese NAFLD patients.

Association of cognitive function and hypoperfusion in Moyamoya disease patients without stroke.

The influence of hypoperfusion on cognition in patients with Moyamoya disease (MMD) is unclear. This study investigated cognitive function changes in MMD patients without stroke and illustrated the relationship between cognitive impairment and hypoperfusion. We prospectively performed a structured battery of seven neurocognitive tests on 115 adult MMD patients without stroke and 82 healthy controls. Hemodynamic assessment was performed using dynamic susceptibility contrast-enhanced MRI. The best subset regression (BSR) strategy was used to identify risk factors. Global cognition (MoCA), speed of information processing (TMT-A), executive function (TMT-B), visuospatial function (CDT), and verbal memory (CAVLT) were significantly poorer in MMD patients without stroke than in healthy controls. The TMT-B score significantly correlated with cerebral blood flow (CBF) in the bilateral lateral frontal lobes, centrum semiovale, and temporal lobes. The TMT-A and CAVLT scores significantly correlated with CBF in the left centrum semiovale (L-CSO) and temporal lobes. According to the BSR results, age, education, white matter lesions, and hypoperfusion of the L-CSO were risk factors for cognitive impairment. Hypoperfusion leads to multiple cognitive impairments in MMD patients without stroke. The perfusion of particular areas may help evaluate the cognitive function of MMD patients and guide therapeutic strategies.

Prone position reduces the risk of patients with mild or moderate COVID-19 progressing to severe or even critical cases: a retrospective study.

BACKGROUND: To investigate whether prone position can reduce the risk of patients with mild or moderate COVID-19 who progress to severe or critical illness. METHODS: The prone position group was treated in prone position on the day of admission in addition to conventional treatment. Indicators such as saturation of pulse oximetry (SpO2), heart rate, blood pressure, respiratory rate, and prone position-related adverse events were recorded before prone ventilation, 5 min after prone position and 30 min after prone position. Meanwhile, the cases of severe and critical patients, the percentage of transformation and the final clinical outcome of this group were analyzed. Conversion rates and mortality were calculated for patients with mild or moderate COVID-19 retrieved from the database who received only conventional care without combined prone positioning as control group. RESULTS: (1) A total of 34 patients were included in prone position group. There were significant differences in SpO2 between the first 4 days after admission and the day of discharge (F = 3.17, P < 0.001). (2) The main complications were back and neck muscle soreness (55.9%), followed by abdominal distension (8.9%). (3) In control group, a total of 4873 cases of mild and moderate patients were included from 19 literatures, with an average deterioration rate of 22.7% and mortality rate of 1.7%. (4) In prone position group, there were no severe or critical transformation cases and also no death cases. The prone position group had a significantly lower deterioration rate when compared with the control group (χ2 = 9.962, P < 0.01). CONCLUSION: Prone position improves SpO2 in patients with mild or moderate COVID-19. It can also reduce the percentage of mild or moderate patients progressing to severe or critical patients. The application of prone position is a simple, feasible, safe and effective treatment method in such patients.

Diagnostic Value and Prognostic Evaluation of Autophagy-Related Protein Expression Level in Sepsis Complicated with Acute Respiratory Distress Syndrome.

Objective: To explore the diagnostic value and prognostic evaluation of the autophagy-related protein expression level among patients with sepsis comorbid with acute respiratory distress syndrome. Methods: A total of 182 sepsis patients were admitted to Naval Medical Center from March 2016 to April 2020 and divided into the acute respiratory distress syndrome and non-ARDS groups. Immunoblotting was employed to identify the expression of autophagy-associated protein from participants' peripheral blood mononuclear cells. Multivariate linear regression analysis was used to examine the association between mortality and the protein expression in sepsis complicated with acute respiratory distress syndrome. Results: Among the 182 patients with sepsis included in this study, 82 patients had acute respiratory distress syndrome and 100 patients did not have acute respiratory distress syndrome. We observed that microtubule-related protein 1A/1B LC3II, Beclin-1, RAB7, and LAMP2 protein expression was significantly decreased in septic patients with ARDS, and p62 was significantly increased. Further receiver operating characteristic curve analysis showed that autophagy-related proteins had a high recognition ability in sepsis complicated with acute respiratory distress syndrome. LAMP2 protein was the best among them, and its specificity was up to 91.46%. In this study, 38 of the 82 patients with sepsis complicated with acute respiratory distress syndrome died, with a mortality rate of 46.34%. We found that the autophagy level was further inhibited in the patients with death, LC3II, Beclin-1, and RAB7. However, the lysosomal-associated membrane protein 2 levels in the survival patients were remarkably higher than that in the dead patients. In addition, the p62 level was lower in survival patients as well. Our results indicated age and SOFA score were the independent risk factors for mortality in septic patients with acute respiratory distress syndrome. Conclusion: The autophagy level is significantly inhibited in septic patients with acute respiratory distress syndrome, and autophagy-associated proteins LC3II, Beclin-1, RAB7, LAMP2, and p62 have good value for the diagnosis and prognosis evaluation of sepsis comorbid with acute respiratory distress syndrome.

White matter damage in patients with mild cognitive impairment in Parkinson's disease.

BACKGROUND: This study investigates the correlation between white matter structural damage and cognitive impairment in patients with Parkinson's disease (PD) and mild cognitive impairment (MCI). METHODS: A total of 40 patients with PD were divided into two groups, i.e., a mild cognitive impairment (PD-MCI) and a normal cognitive (PDN) group, and 20 healthy patients were enrolled as the control group. Changes in the white matter structure of patients with PD were evaluated using diffusion tensor imaging (DTI), and cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA) scale and Mini-Mental State Examination (MMSE). Finally, the correlations between the two groups were analyzed. RESULTS: The Unified Parkinson's Disease Rating Scale score was significantly higher in the PD-MCI than in the PDN group (P=0.008). The total MoCA and MMSE scores in the PD-MCI group were significantly lower than in the PDN and control groups (P<0.01). Patients in PDMCI group were tested by MMSE scale, and the abnormal score rate was 60.0%. Among them, 8 PD patients with normal MMSE total score were found to have mild cognitive impairment by MoCA evaluation. When compared with the PDN and control groups, the MoCA scores for visual space, which is assessed as part of the MoCA scale and generally represents bilateral parietal function; naming; memory; and attention were significantly lower in the PD-MCI group (P<0.001). When compared with the PDN group, the fractional anisotropy (FA) values for the right parietal and left occipital lobes were significantly lower in the PD-MCI group (P=0.005; P=0.018). The relationship between MoCA value and right parietal white matter and left occipital white matter was 0.555, 0.474, respectively. A Pearson's correlation test was conducted to compare the FA values and MoCA scores of the various brain areas in the PD-MCI group and revealed a significant positive correlation between the MoCA score and the white matter of the right parietal and left occipital lobes (P<0.01). CONCLUSIONS: Patients with PD experience early cognitive impairment, and the MoCA scale can be used for early screening. In addition, the DTI of white matter can highlight early white matter damage. In the current study, the damaged brain areas displayed by DTI were consistent with areas showing decreased MoCA scores and were positively correlated with the severity of PD.

[Effect of grape seed extract on oxidative stress and pathological changes of aorta in rats with chronic periodontitis and arteriosclerosis].

PURPOSE: To investigate the effect of grape seed extract on pathological changes of aorta in rats with chronic periodontitis and arteriosclerosis, and to analyze the possible mechanism. METHODS: Fifteen SPF male rats with chronic periodontitis and arteriosclerosis were randomly divided into three groups, i.e., model group(n=5), low dose of grape seed extract group (n=5), high dose of grape seed extract group (n=5) , and control group (n=10). The rats in the low and high dose groups were treated with 40 mg·kg-1·d-1 and 80 mg·kg-1·d-1 for 4 weeks respectively, while the rats in the normal control group and the model group were treated with the same amount of normal saline at the same time. The maximal intima-media thickness(IMT) of abdominal aorta was measured by H-E staining, the activity of SOD and the content of MDA in serum were measured by colorimetry, the content of GSH-px in serum and serum levels of inflammatory factor (TNF-α) and interleukin-6(IL-6) were detected by ELISA. p38 mitogen-activated protein kinase/nuclear transcription factor Kappa B p65(p38 MAPK/NF-κB p65) pathway was detected by Western blotting. SPSS 20.0 software package was used for statistical analysis. RESULTS: In the model group, the intima of abdominal aorta was irregularly thickened, with a lot of inflammatory cell infiltration, and arterial lesions appeared. In the low-and high-dose groups of grape seed extract, the plaque of abdominal aorta intima decreased and inflammatory cells reduced significantly, arterial vascular disease was improved, and the improvement was more obvious in high dose group than in low dose group. Compared with the control group, the levels of IMT, serum MDA, TNF-α, IL-6, p-p38MAPK/p38MAPK, NF-κB p65 and serum SOD and GSH-px in the model group were increased, while those in the model group were decreased(P＜0.05); the levels of IMT, serum MDA, TNF-α, IL-6, p-p38MAPK/p38MAPK, NF-κB p65 and SOD, GSH-px were decreased in the low and high dose groups(P＜0.05). CONCLUSIONS: Grape seed extract can inhibit the oxidative stress level and inflammatory reaction in serum of chronic periodontitis with arteriosclerosis rats, thus improving the intimal lesion of aorta, possibly by inhibiting the activation of p38MAPK/NF-κB p65 pathway.

Expression and localization of Sox10 during hair follicle morphogenesis and induced hair cycle.

Sox transcription factors play many diverse roles during development, including regulating stem cell states, directing differentiation, and influencing the local chromatin landscape. Sox10 has been implicated in the control of stem/progenitor activity and epithelial-mesenchymal transition, yet it has not been studied in relation to the hair follicle cycle or hair follicle stem cell (HFSC) control. To elucidate the role of Sox10 in hair follicle cycle control, we performed immunohistochemical and immunofluorescence analysis of its expression during hair morphogenesis, the postnatal hair cycle, and the depilation-induced murine hair follicle cycle. During hair follicle morphogenesis, Sox10 was expressed in the hair germ and peg. In telogen, we detected nuclear Sox10 in the hair bulge and germ cell cap, where HFSCs reside, while in anagen and catagen, Sox10 was detected in the epithelial portion, such as the strands of keratinocytes, the outer root sheath (ORS) in anagen, and the regressed epithelial strand of hair follicle in catagen. These results suggest that Sox10 may be involved in early hair follicle morphogenesis and postnatal follicular cycling.

Application of virtual scenario simulation combined with problem-based learning for paediatric medical students.

OBJECTIVES: To examine the application and effects of virtual scenario simulation combined with problem-based learning (PBL) in teaching paediatric medical students. METHODS: Participants were 300 paediatric medical students randomly divided into a study group and control group. Students in the study group were taught using virtual scenario simulation combined with PBL; students in the control group were taught using conventional teaching methods. Academic performance, knowledge of paediatrics, self-evaluation of comprehensive ability and degree of learning satisfaction were evaluated. RESULTS: Students in the study group showed considerably higher academic performance and noticeably higher classroom performance. Paediatric knowledge, comprising initiating communication, collecting information, giving information, understanding the paediatric patient and concluding communication, was higher for students in the study group. The degree of learning satisfaction was higher for students in the study group. CONCLUSION: Virtual scenario simulation combined with PBL can effectively improve students' academic performance, mastery of paediatric knowledge, comprehensive ability evaluation and learning satisfaction. The broader application of this approach should be explored for medical student education.

Auricular acupressure for cancer-related fatigue during lung cancer chemotherapy: a randomised trial.

PURPOSE: To evaluate the effect of auricular acupressure (AA) on cancer-related fatigue (CRF), sleep disturbance and anxiety in lung cancer patients undergoing chemotherapy. MATERIALS AND METHODS: Patients were recruited from the respiratory department of a general hospital and were randomised into three groups. A 9-week course of AA using Semen Vaccariae (SV) (Group A)/AA using magnetic beads (Group B)/routine care (Group C) was implemented. CRF scores were used as the primary outcome while the sleep and anxiety scores were the secondary outcomes. Analysis of variance and least significant difference t-test were used to determine the intergroup differences and paired-sample t-test was used for the intragroup comparison. RESULTS: 100 lung cancer patients undergoing chemotherapy were included. Compared with Group C, AA could significantly alleviate CRF (F:24.63, p<0.01), especially for physical and affective fatigue and Group A was more effective for managing physical fatigue than Group B in per-protocol (PP) (-1.75 (-2.69 to -0.82), p<0.01)/Intention to Treat analysis (ITT) (-1.41 (-2.39 to -0.41), p=0.01) analysis. However, AA had no effect on cognitive fatigue. Compared with Group C, only Group A produced significant improvements in sleep quality in PP analysis (-1.17 (-2.23 to -0.10), p=0.03) while it yielded negative results in ITT analysis (-0.82 (-1.74 to 0.10), p=0.08). Compared with Group C, AA could significantly reduce anxiety in PP analysis (F:9.35, p<0.01) while there was no statistical difference between Group B and Group C (-0.95 (-2.81 to 0.90), p=0.31), Group A and Group B (-1.26 (-3.12 to 0.59), p=0.18) in ITT analysis. CONCLUSION: AA can alleviate CRF of lung cancer patients undergoing chemotherapy, especially for physical and affective fatigue. AA using SV is more effective for physical fatigue while AA using magnetic beads works better for anxiety. However, AA cannot improve the sleep quality. TRIAL REGISTRATION NUMBER: ISRCTNregistry (ISRCTN16408424).

[Clinical features of asymptomatic or subclinical COVID-19 in children].

OBJECTIVE: To study the clinical features of asymptomatic or subclinical coronavirus disease 2019 (COVID-19) in children. METHODS: A retrospective analysis was performed for the clinical data of 53 children who were confirmed with asymptomatic or subclinical COVID-19, including epidemiological history, clinical typing, co-infection, time to clearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid in nasopharyngeal swabs, laboratory examination results, length of hospital stay, and treatment outcome. RESULTS: The children with asymptomatic or subclinical COVID-19 accounted for 30.5% (53/174) in children with COVID-19 hospitalized in the COVID-19 ward of Wuhan Children's Hospital. All cases occurred with familial aggregation. Among the 53 children, 35 (66%) had asymptomatic infection and 18 (34%) had subclinical infection. Mycoplasma infection was found in 17 children (32%). For the 53 children, the mean time to clearance of SARS-CoV-2 nucleic acid in nasopharyngeal swabs was 9±4 days. Most laboratory markers were maintained within the normal range. The mean hospital stay was 11±4 days. Lung CT of 18 children with subclinical COVID-19 showed ground-glass opacities, linear opacities, and patchy opacities, with relatively limited lesions. CONCLUSIONS: There is a high proportion of children with asymptomatic or subclinical COVID-19 among the children with COVID-19 hospitalized in the COVID-19 ward. The transmission risk of asymptomatic or subclinical COVID-19 should be taken seriously.

Lichen Simplex Chronicus Secondary to Scald Injury and Skin Flap Transplantation.

A 50-year-old woman had suffered from chronic pruritic plaque located on right retroauricular area for around 16 years, which was diagnosed as lichen simplex chronicus. Seventeen years ago, patient had multiple scalded areas distributed throughout the body and underwent autologous skin flap transplantation for the right retroauricular wound. After the wound healed, patient started experiencing paresthesia continuously on the skin grafted area and could not resist scratching. To our knowledge, this is the first reported case of lichen simplex chronicus secondary to scald injury and skin flap transplantation. We successfully treated this patient with dyclonine hydrochloride cream 1% and desonide cream 0.05%.

Endometrial clear cell carcinoma invading the right oviduct with a cooccurring ipsilateral oviduct adenomatoid tumor: A case report.

BACKGROUND: To investigate the clinicopathological features of endometrial clear cell carcinoma that has invaded the right oviduct with a cooccurring ipsilateral oviduct adenomatoid tumor. CASE SUMMARY: A case of endometrial clear cell carcinoma invading the right oviduct with a cooccurring ipsilateral oviduct adenomatoid tumor was collected and analyzed using pathomorphology and immunohistochemistry. Endometrial clear cell carcinoma cells were distributed in a solid nest, papillary, shoe nail-like, and glandular tube-like distribution. There was infiltrative growth, and tumor cells had clear cytoplasm and obvious nuclear heteromorphism. The cancer tissue was necrotic and mitotic. The cancer tissue invaded the right oviduct. The ipsilateral oviduct also had an adenomatoid tumor. The adenomatoid tumor was arranged in microcapsules lined with flat or cubic cells that were surrounded by smooth muscle tissue. The adenomatoid tumor cells were round in shape. CONCLUSION: Clear cell carcinoma of the endometrium can invade the oviduct and occur simultaneously with tubal adenomatoid tumors. Upon pathological diagnosis, one should pay close attention to distinguishing whether an endometrial clear cell carcinoma is invading the oviduct or whether it is accompanied by an adenomatoid tumor of the oviduct. Immunohistochemistry is helpful to differentiate these two disease entities. Endometrial clear cell carcinomas express Napsin-A and P16 and are negative for estrogen receptor and progesterone receptor. The presence of endometrial clear cell carcinoma does not affect the expression of CK and calretinin in adenomatoid tumors.

[Effects of water-nitrogen combination on dry matter, nitrogen accumulation and yield of winter wheat]. / æ°´æ°®ç»„åˆå¯¹å†¬å°éº¦å¹²ç‰©è´¨åŠæ°®ç´ ç§¯ç´¯å’Œäº§é‡çš„å½±å“.

In two growing seasons of wheat (2015-2017), we conducted a field trial with Taishan 28 in Tai'an Academy of Agricultural Science Feicheng experimental base, Tai'an City, Shandong Province. There were four irrigation levels of 150 (A1), 300 (A2), 450 (A3), and 600 (A4) m3·hm-2, and four nitrogen application levels of 90 (B1), 135 (B2), 180 (B3), and 225 (B4) kg·hm-2. We examined the effects of the combination effects of irrigation and nitrogen on dry matter accumulation and transport, nitrogen accumulation and transport, water consumption and utilization, photosynthetic characteristics, wheat grain yield and yield components of wheat. The results showed that dry matter accumulation, nitrogen accumulation, vegetative organs production, storage and the transportation volume to grains of the dry matter and nitrogen, and dry matter and nitrogen accumulation of grain in the mature stage of wheat all reached the maximum in A3B3 treatment, which were significantly different from other treatments. Under all the nitrogen treatments, soil water consumption in the 60-200 cm soil layer was A3>A4>A2>A1. Water use efficiency and nitrogen use efficiency in A3B3 treatment were higher than that under A3B4, A4B3 and A4B4. The net photosynthetic rate, stomatal conductance and transpiration rate of flag leaves from 7 to 28 days after flowe-ring were all significantly higher in A3B3 treatment, which was conducive to the photosynthetic synthesis of carbohydrates in wheat. The interaction effect of water and nitrogen addition significantly affected grain yield and yield components. Wheat yield was the highest in A3B3 treatment which reached at 9400 kg·hm-2. In conclusion, the treatment with irrigation of 450 m3·hm-2 and nitrogen of 180 kg·hm-2 could significantly improve dry matter and nitrogen accumulation, and promote transportation volume of the dry matter and nitrogen to grain. Compared with the high water and nitrogen treatment, it could effectively increase water use efficiency and nitrogen use efficiency, enhance photosynthetic capacity of flag leaf, produce more carbohydrate, and increase grain yield.

Twelve formyl phloroglucinol meroterpenoids from the leaves of Eucalyptus robusta.

Twelve formyl phloroglucinol meroterpenoids (FPMs) were isolated from the leaves of Eucalyptus robusta Smith. Their structures were elucidated via spectroscopic data analysis, the circular dichroism (CD) exciton chirality method, Rh2(OCOCF3)4-induced CD experiments, and application of the Snatzke chirality rules. Eucalrobusones Q, S, and X are the first FPMs that have been identified in which the C-7' of phloroglucinol is linked to the C-15 of cadinane, the C-4 of cubebane, and the C-8 of menthane, respectively. (+)-Eucalrobusone X exhibited the most potent antifungal ability against Candida albicans with a MIC50 value of 10.78 µg/mL, and eucalrobusone U exhibited the greatest anti-C. glabrata activity with MIC50 value of 1.53 µg/mL.

Microporous Luminescent Metal-Organic Framework for a Sensitive and Selective Fluorescence Sensing of Toxic Mycotoxin in Moldy Sugarcane.

Food contamination by toxic mycotoxins not only causes a considerable loss in economy, but importantly poses a huge threat to human health through accidental ingestion. Hence, it is an ongoing and imperative need to develop a convenient, cost-effective method for the detection of the mycotoxin-infected agricultural commodities. To this end, we herein fabricated a novel metal-organic framework-derived composite material that displays a strong solid-state emission in the visible region, by attaching a frequently used fluorescent label, fluorescein isothiocyanate (FITC), via guest adsorption. Significantly, owing to the inherent pH-responsive conformational changes of FITC, the resulting composite material provides, to the best of our knowledge, the first example of the sensitive and selective fluorescence sensing toward 3-nitropropionic acid, which, as a major naturally occurring mycotoxin in moldy sugarcane, has been closely linked to poisoning episodes in human beings and animals.

MicroRNA-34a modulates the Notch signaling pathway in mice with congenital heart disease and its role in heart development.

The objective of the study was to elucidate the mechanism by which microRNA-34a (miR-34a) influences heart development and participates in the pathogenesis of congenital heart disease (CHD) by targeting NOTCH-1 through the Notch signaling pathway. Forty D7 pregnant mice were recruited for the purposes of the study and served as the CHD (n=20, successfully established as CHD model) and normal (n=20) groups. The positive expression of the NOTCH-1 protein was evaluated by means of immunohistochemistry. Embryonic endocardial cells (ECCs) were assigned into the normal, blank, negative control (NC), miR-34a mimics, miR-34a inhibitors, miR-34a inhibitors+siRNA-NOTCH-1, siRNA-NOTCH-1, miR-34a mimics+NOTCH-1 OE and miR-34a mimics+crispr/cas9 (mutant NOTCH-1) groups. The expressions of miR-34a, NOTCH-1, Jagged1, Hes1, Hey2 and Csx in cardiac tissues and ECCs were determined by both RT-qPCR and western blotting methods. MTT assay and flow cytometry were conducted for cell proliferation and apoptosis measurement. A dual luciferase reporter assay was applied to demonstrate that NOTCH-1 was the target gene of miR-34a. In comparison to the normal group, the expressions of miR-34a, Jagged1, Hes1 and Hey2 displayed up-regulated levels, while the expressions of NOTCH-1 and Csx were down-regulated in the CHD group. Compared with the blank and NC groups, the miR-34a mimics and siRNA-NOTCH-1 groups displayed reduced expressions of NOTCH-1 and Csx as well as a decreased proliferation rate, higher miR-34a, Jagged1, Hes1 and Hey2 expressions and an increased rate of apoptosis; while an reverse trend was observed in the miR-34a inhibitors group. The expressions of MiR-34a recorded increased levels in the miR-34a mimics+NOTCH-1 OE and miR-34a mimics+crispr/cas9 (mutant NOTCH-1) groups, however no changes in the expressions of NOTCH-1, Jagged1, Hes1, Hey2, Csx, as well as cell proliferation and apoptosis were observed when compared to the blank and NC groups. The results of our study demonstrated that miR-34a increases the risk of CHD through its downregulation of NOTCH-1 by modulating the Notch signaling pathway.