Genome-wide identification and structural analysis of the BMP gene family in Triplophysa dalaica.

BACKGROUND: Bone morphogenetic proteins (BMPs) are part of the transforming growth factor beta (TGF-ß) superfamily and play crucial roles in bone development, as well as in the formation and maintenance of various organs. Triplophysa dalaica, a small loach fish that primarily inhabits relatively high elevations and cooler water bodies, was the focus of this study. Understanding the function of BMP genes during the morphogenesis of T. dalaica helps to clarify the mechanisms of its evolution and serves as a reference for the study of BMP genes in other bony fishes. The data for the T. dalaica transcriptome and genome used in this investigation were derived from the outcomes of our laboratory sequencing. RESULTS: This study identified a total of 26 BMP genes, all of which, except for BMP1, possess similar TGF-ß structural domains. We conducted an analysis of these 26 BMP genes, examining their physicochemical properties, subcellular localization, phylogenetic relationships, covariance within and among species, chromosomal localization, gene structure, conserved motifs, conserved structural domains, and expression patterns. Our findings indicated that three BMP genes were associated with unstable proteins, while 11 BMP genes were located within the extracellular matrix. Furthermore, some BMP genes were duplicated, with the majority being enriched in the GO:0008083 pathway, which is related to growth factor activity. It was hypothesized that genes within the BMP1/3/11/15 subgroup (Group I) play a significant role in the growth and development of T. dalaica. By analyzing the expression patterns of proteins in nine tissues (gonad, kidney, gill, spleen, brain, liver, fin, heart, and muscle), we found that BMP genes play diverse regulatory roles during different stages of growth and development and exhibit characteristics of division of labor. CONCLUSIONS: This study contributes to a deeper understanding of BMP gene family member expression patterns in high-altitude, high-salinity environments and provides valuable insights for future research on the BMP gene family in bony fishes.

Contrast extravasation mimicking intracerebral and intraventricular hemorrhage after intravenous thrombolytic treatment of ischemic stroke: a case report.

BACKGROUND: Although contrast extravasation on follow-up head computed tomography (CT) is frequently visualized after endovascular treatment, this phenomenon is rare after intravenous thrombolytic treatment in patients with acute ischemic stroke (AIS). Here, we report a case of contrast extravasation mimicking intracerebral hemorrhage (ICH) with intraventricular extension after intravenous thrombolytic treatment and computed tomography angiography (CTA). CASE PRESENTATION: A 52-year-old man presented with right-sided hemiparesis and hypoesthesia. Initial non-contrast head CT was negative for intracranial hemorrhage and acute ischemic changes. He received intravenous treatment with tenecteplase 3.8 h after the onset of stroke. CTA of the head and neck was performed at 4.3 h after stroke onset. It showed no stenosis or occlusion of the carotid and major intracranial arteries. At about 1.5 h after CTA, the right-sided hemiparesis deteriorated, accompanied by drowsiness, aphasia, and urinary incontinence. Immediate head CT showed hyperdense lesions with mild space-occupying effect in the left basal ganglia and both lateral ventricles. The hyperdense lesions were reduced in size on follow-up CT after 5 h. Two days later, CT showed that the hyperdense lesions in the lateral ventricles almost completely disappeared and only a small amount remained in the infarcted area. CONCLUSIONS: Contrast extravasation into the brain tissue and lateral ventricles, mimicking ICH with intraventricular extension, could occur after intravenous thrombolytic treatment and CTA in a patient with AIS, which might lead to misdiagnosis and wrong treatment of the patient. The rapid resolution of intracranial hyperdense lesions is key to differentiate contrast extravasation from ICH on serial non-enhanced CT.

Prediction of Hydrogen Abstraction Rate Constants at the Allylic Site between Alkenes and OH with Multiple Machine Learning Models.

Hydrogen abstraction reactions between hydrocarbons and hydroxyl radicals are important propagation steps in radical chain reactions, playing a crucial role in atmospheric and combustion chemistry. This study focuses on predicting the rate constants of the prototype of the reaction class of hydrogen abstractions, i.e., the primary allylic hydrogen abstraction from alkenes by the OH radical, via utilizing machine learning (ML) methods. Specifically, three distinct models, namely, feedforward neural network (FNN), support vector regression (SVR), and Gaussian process regression (GPR), have been employed to construct robust ML models for prediction. We proposed a novel strategy that seamlessly integrates descriptor preprocessing, a pairwise linear correlation analysis, and a model-specific Wrapper method to enhance the effectiveness of the feature selection procedure. The selected feature subset was then evaluated using two cross-validation techniques, i.e., leave-one-group-out (LOGO) and K-fold cross-validations, for each of the three ML models (FNN, SVR, and GPR) to assess their predictive and stability performance. The results demonstrate that the FNN model, trained with seven representative descriptors, achieves superior performance compared to the other two methods. For the FNN model, the average percentage deviation is 39.06% on the test set by performing LOGO cross-validation, while the repeated 10-fold cross-validation achieves a percentage prediction deviation of 19.1%. Two larger alkenes with 10 carbons were selected to test the prediction performance of the trained FNN model on primary allylic hydrogen abstraction. Results show that the kinetic predictions follow well the modified three-parameter Arrhenius equation, indicating the reliable performance of FNN in predicting hydrogen abstraction rate constants, especially for the primary allylic site. Hopefully, this work can shed useful light on the application of ML in generating chemical kinetic parameters of hydrocarbon combustion chemistry.

Structure-Based Reaction Descriptors for Predicting Rate Constants by Machine Learning: Application to Hydrogen Abstraction from Alkanes by CH3/H/O Radicals.

Accurate determination of the thermal rate constants for combustion reactions is a highly challenging task, both experimentally and theoretically. Machine learning has been proven to be a powerful tool to predict reaction rate constants in recent years. In this work, three supervised machine learning algorithms, including XGB, FNN, and XGB-FNN, are used to develop quantitative structure-property relationship models for the estimation of the rate constants of hydrogen abstraction reactions from alkanes by the free radicals CH3, H, and O. The molecular similarity based on Morgan molecular fingerprints combined with the topological indices are proposed to represent chemical reactions in the machine learning models. Using the newly constructed descriptors, the hybrid XGB-FNN algorithm yields average deviations of 65.4%, 12.1%, and 64.5% on the prediction sets of alkanes + CH3, H, and O, respectively, whose performance is comparable and even superior to the corresponding one using the activation energy as a descriptor. The use of activation energy as a descriptor has previously been shown to significantly improve prediction accuracy ( Fuel 2022, 322, 124150) but typically requires cumbersome ab initio calculations. In addition, the XGB-FNN models could reasonably predict reaction rate constants of hydrogen abstractions from different sites of alkanes and their isomers, indicating a good generalization ability. It is expected that the reaction descriptors proposed in this work can be applied to build machine learning models for other reactions.

Identification and Functional Analysis of Two Novel Genes-Geranylgeranyl Pyrophosphate Synthase Gene (AlGGPPS) and Isopentenyl Pyrophosphate Isomerase Gene (AlIDI)-from Aurantiochytrium limacinum Significantly Enhance De Novo ß-Carotene Biosynthesis in Escherichia coli.

Precursor regulation has been an effective strategy to improve carotenoid production and the availability of novel precursor synthases facilitates engineering improvements. In this work, the putative geranylgeranyl pyrophosphate synthase encoding gene (AlGGPPS) and isopentenyl pyrophosphate isomerase encoding gene (AlIDI) from Aurantiochytrium limacinum MYA-1381 were isolated. We applied the excavated AlGGPPS and AlIDI to the de novo ß-carotene biosynthetic pathway in Escherichia coli for functional identification and engineering application. Results showed that the two novel genes both functioned in the synthesis of ß-carotene. Furthermore, AlGGPPS and AlIDI performed better than the original or endogenous one, with 39.7% and 80.9% increases in ß-carotene production, respectively. Due to the coordinated expression of the 2 functional genes, ß-carotene content of the modified carotenoid-producing E. coli accumulated a 2.99-fold yield of the initial EBIY strain in 12 h, reaching 10.99 mg/L in flask culture. This study helped to broaden current understanding of the carotenoid biosynthetic pathway in Aurantiochytrium and provided novel functional elements for carotenoid engineering improvements.

Association of plaque enhancement on vessel wall MRI and the phosphodiesterase 4D variant with stroke recurrence in patients with symptomatic intracranial atherosclerosis.

PURPOSE: Vessel wall MRI (VW-MRI) can be used to evaluate the nature of intracranial atherosclerosis (ICAS) plaque in vivo. Phosphodiesterase 4D (PDE4D) participates in stroke development. This study aims to explore the value of VW-MRI findings and the PDE4D gene variant in predicting stroke recurrence in patients with ICAS. METHODS: We prospectively recruited 324 symptomatic ICAS patients. VW-MRI was performed to determine luminal and wall changes. PDE4D gene single-nucleotide polymorphisms (SNPs)-namely, SNP32, SNP83, and SNP87-were determined by direct sequencing. The risk factors of stroke recurrence were analyzed using the multivariate Cox proportional hazards model. RESULTS: Of the 324 subjects, 97 (29.9%) experienced recurrent ischemic stroke during the follow-up period. A total of 254 patients (78.4%) showed plaque enhancement; 87 of these patients experienced stroke recurrence. The CT/CC genotype frequencies of PDE4D83 were significantly higher in participants with recurrent stroke than in patients without stroke recurrence (p = 0.019 and p < 0.001, respectively). However, the PDE4D32 and PDE4D87 variants were not correlated with recurrent stroke. Multivariate analysis showed that plaque enhancement from VW-MRI (HR 4.52, 95% CI 2.35-8.73, p < 0.001) and the PDE4D83 variant (HR 7.43, 95% CI 1.75-31.87, p = 0.005) were independently correlated with stroke recurrence. Kaplan-Meier curves showed significant differences in stroke recurrence rates between the plaque-enhanced group and the non-enhanced group (p < 0.001) and between the PDE4D83 variant carriers and noncarriers (p = 0.002). CONCLUSION: Plaque enhancement on VW-MRI and the presence of the PDE4D83 variant are associated with ischemic stroke recurrence in subjects with symptomatic ICAS.

Blood copper excess is associated with mild cognitive impairment in elderly Chinese.

BACKGROUND: Copper is associated with mild cognitive impairment (MCI). However, there is a lack of relevant population studies with large sample sizes. AIMS: This study used baseline data from a cohort study to determine the distribution characteristics of MCI in the elderly and to estimate the association between whole blood copper concentrations and MCI. METHODS: MCI status was screened by the Mini-Mental State Examination (MMSE) scale and Activities of Daily Living (ADL) scale. The concentration of copper in whole blood was determined by Inductively Coupled Plasma Mass Spectrometer (ICP-MS). RESULTS: A total of 1057 subjects with an average age of 71.82 ± 6.45 years were included in this study. There were 215 patients with MCI, and the prevalence of MCI was 20.34%. After adjusting for general demographic variables, logistic regression analysis showed that the risk of MCI in the elderly with high copper level was 1.354 times higher than that in the elderly with low copper level (OR 1.354, 95% CI 1.047-1.983, P = 0.034). CONCLUSION: In this study, it was found that the prevalence of MCI was different in gender, age, education level and other aspects, and a higher copper level in the elderly was significantly related to the occurrence of MCI. The association was stronger in older adults and men.

First report of Cladosporium tenuissimum causing leaf spot of Arachis hypogaea in China.

Peanut (Arachis hypogaea L.), one of the most important oilseed crops in tropical and subtropical regions of the world (Kumar and Kirti 2011), is widely cultivated for its high protein and oil content in seeds. In August 2019, about 30% of A. hypogaea plants were found infected by leaf spot in the peanut-growing regions of Shandong Province, China. Disease symptoms appeared as the irregular and brown necrotic lesions on leaves that were 0.5 to 5.0 mm in diam. Twenty symptomatic plants were randomly sampled from peanut planting areas in Weihai and Yantai City. Small pieces (3 mm2) were cut from lesions, dipped in a 0.5% NaClO for 10 min, rinsed three times with sterilized distilled water, dried, placed onto potato-dextrose agar (PDA), and incubated in the dark at 25°C for 10 days. Three typical Cladosporium-like strains were isolated from diseased leaves of peanut. The colonies were grey to olivaceous green, reverse olivaceous black and woolly. The conidiophores were solitary, macronematous, unbranched or branched, straight or flexuous, cylindrical, slightly swollen at the apex, smooth. Conidiogenous cells were integrated, terminal and intercalary, with numerous loci on nodulose swelling. Ramoconidia were cylindrical, oblong, fusiform, 8.0 to 19.5×2.0 to 4.5 µm, aseptate or 1 septum, pale brown. Conidia were catenate, in densely branched chains, ellipsoid, ovoid, limoniform, aseptate, 4.0 to 11.5×2.5 to 5.5 µm, smooth, with conspicuous hila. The conidia easily break off from the chains. The morphological characteristics of these isolates matched the descriptions of Cladosporium tenuissimum (Bensch et al. 2010). For the molecular identification, the partial actin (act) and translation elongation factor 1-alpha (tef1) genes were amplified and sequenced using the respective primers ACT-512F/ACT-783R and EF1-728F/EF1-986R (Carbone and Kohn 1999). The representative sequences, deposited in GenBank (act: OL332701, OL332702 and OL332703; tef1: OL322090, OL322091 and OL322092), exhibited 99.6% and 100% identical to C. tenuissimum ex-type isolate CBS 125995 (HM148687 and HM148442). Phylogenetic analysis was done by Neighbor-Joining (NJ) analysis based on act+tef1 sequences. These three isolates were identified as C. tenuissimum by morphological and molecular characteristics. Pathogenicity of each C. tenuissimum isolate was tested on peanut in the greenhouse at 28°C with 75% relative humidity. Twenty plants of A. hypogaea were inoculated with the conidial suspension (1.0 × 105 conidia/ml) on the leaf surface. Ten plants were mock inoculated with sterile water as controls. Within 2 weeks, inoculated plants exhibited dark necrotic lesions on leaves which were similar to the symptoms observed in the field, while the mock inoculated plants remained symptomless. The fungal pathogen which was reisolated from inoculated rather than mock inoculated leaf tissues was identical to the original pathogen on the basis of morphological and molecular analysis, confirming Koch's postulates. To our knowledge, this is the first report of leaf spot caused by C. tenuissimum on peanut in China. The C. tenuissimum infection poses a serious threat by reducing the yield and quality of peanut in Shandong Province. This research is especially valuable to enhance epidemiological studies and implement effective control strategies.

Maternal periconceptional folic acid supplements use and fetus risk for limb defects.

BACKGROUND: Associations between the periconceptional folic acid only (FAO) or multiple micronutrients containing folic acid (MMFA) supplementation and risk for limb defects are inconsistent. OBJECTIVE: To explore the association between periconceptional folic acid supplements use and risk for limb defects, including clubfoot, polydactyly, syndactyly, and limb deficiencies. METHODS: Data were derived from a cohort based on a pregnancy registry in a district of Beijing, China, from 2013 to 2018. Information on maternal periconceptional FAO and MMFA supplementation was collected via face-to-face interviews at first trimester. Pregnancy outcomes including limb defects were ascertained in livebirths, stillbirths, and elective pregnancy terminations and were recorded into the system. Propensity score methods were used to adjust for potential confounders. RESULTS: A total of 63 969 women with a singleton delivery were included. The overall prevalence of limb defects was 47.5 per 10 000 (n = 63 969) singleton deliveries. Decreased prevalence of limb defects was found among FAO/MMFA users compared with women who did not take supplements (nonusers) (46.1 vs. 61.9 per 10 000 births, adjusted risk ratio [RR] 0.80, 95% confidence interval [CI] 0.56, 1.12). Compared with nonusers (n = 6462, 10.2%), women who took either FAO (n = 26 567, 42.0%) or MMFA (n = 30 259, 47.8%) had a lower risk for total clubfoot (RR 0.40, 95% CI 0.20, 0.84), and for isolated clubfoot (RR 0.41, 95% CI 0.17, 0.97). For other limb defects except clubfoot, FAO supplementation did not appear to be associated with reduced risk, while MMFA supplementation group had 30%-50% reduced risks for other limb defects. A lower risk for limb defects or isolated limb defects was found with MMFA supplementation when FAO supplementation was used as a control. CONCLUSIONS: Maternal periconceptional supplements with either FAO or MMFA had inverse association with clubfoot in offspring, and MMFA was associated with lower risk for isolated limb defects compared with FAO.

Predicting Rate Constants of Hydroxyl Radical Reactions with Alkanes Using Machine Learning.

The hydrogen abstraction reactions of the hydroxyl radical with alkanes play an important role in combustion chemistry and atmospheric chemistry. However, site-specific reaction constants are difficult to obtain experimentally and theoretically. Recently, machine learning has proved its ability to predict chemical properties. In this work, a machine learning approach is developed to predict the temperature-dependent site-specific rate constants of the title reactions. Multilayered neural network (NN) models are developed by training the site-specific rate constants of 11 reactions, and several schemes are designed to improve the prediction accuracy. The results show that the proposed NN models are robust in predicting the site-specific and overall rate constants.

Associations between prenatal exposure to cadmium and lead with neural tube defect risks are modified by single-nucleotide polymorphisms of fetal MTHFR and SOD2: a case-control study.

BACKGROUND: Prenatal exposure to heavy metals is implicated in the etiology of birth defects. We investigated whether concentrations of cadmium (Cd) and lead (Pb) in umbilical cord tissue are associated with risk for neural tube defects (NTDs) and whether selected genetic variants of the fetus modify their associations. METHODS: This study included 166 cases of NTD fetuses/newborns and 166 newborns without congenital malformations. Umbilical cord tissue was collected at birth or elective pregnancy termination. Cd and Pb concentrations were assessed by inductively coupled plasma-mass spectrometry, and 20 single-nucleotide polymorphisms (SNPs) in 9 genes were genotyped. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the risk for NTDs in association with metal concentrations or genotype using logistic regression. Multiplicative-scale interactions between the metals and genotypes on NTD risk were assessed with logistic regression, and additive-scale interactions were estimated with a non-linear mixed effects model. RESULTS: Higher concentrations of Cd were observed in the NTD group than in the control group, but no difference was found for Pb. Concentrations of Cd above the median level showed a risk effect, while the association between Pb and NTD risk was not significant in univariate analyses. The association of Cd was attenuated after adjusting for periconceptional folic acid supplementation. Fetuses with the AG and GG genotypes of rs4880 in SOD2 (superoxide dismutase 2) tended to have a lower risk, but fetuses with the CT and TT genotypes of rs1801133 in MTHFR (5,10-methylenetetrahydrofolatereductase) have a higher risk for NTDs when compared to their respective wild-type. rs4880 and Cd exhibited a multiplicative-scale interaction on NTD risk: the association between higher Cd and the risk for NTDs was increased by over fourfold in fetuses carrying the G allele [OR 4.43 (1.30-15.07)] compared to fetuses with the wild-type genotype. rs1801133 and Cd exposure showed an additive interaction, with a significant relative excess risk of interaction [RERI 0.64 (0.02-1.25)]. CONCLUSIONS: Prenatal exposure to Cd may be a risk factor for NTDs, and the risk effect may be enhanced in fetuses who carry the G allele of rs4880 in SOD2 and T allele of rs1801133 in MTHFR.

Effects of different probiotic combinations on the components and bioactivity of Spirulina.

Spirulina acts as a good dietary nutritional supplement. However, few research studies have been conducted on its fermentation. Three groups of probiotic combinations, lactic acid bacteria, Bacillus strains, and their mixture, were used to investigate Spirulina fermentation. The results showed that lactic acid bacteria significantly increased the content of amino acids and the ratio of essential amino acids to total amino acids in the fermented Spirulina, compared with the unfermented Spirulina, and this trend was enhanced by the strains' mixture. However, compared to unfermented Spirulina, the amino acid levels were significantly decreased after fermentation with Bacillus strains and so was the total free amino acid and essential amino acid content. Fermentation significantly reduced the contents of the offensive components of Spirulina, with significant differences among the three mixed bacterial treatments. Moreover, Bacillus strain fermentation increased the contents of flavonoids and polyphenols compared to the unfermented Spirulina, and significantly enhanced 1,1-diphenyl-2-trinitrophenylhydrazine free-radical scavenging ability and total antioxidant ability. On the contrary, treatments with lactic acid bacteria and the mixture of lactic acid bacteria and Bacillus strains endowed the fermented supernatants with good antibacterial ability. The results showed that probiotic fermentation has a good effect on Spirulina and can serve as a new procedure for developing new Spirulina-containing food items.

Clinical value of bedside abdominal sonography performed by certified sonographer in emergency evaluation of blunt abdominal trauma.

PURPOSE: To investigate the accuracy and efficiency of bedside ultrasonography application performed by certified sonographer in emergency patients with blunt abdominal trauma. METHODS: The study was carried out from 2017 to 2019. Findings in operations or on computed tomography (CT) were used as references to evaluate the accuracy of bedside abdominal ultrasonography. The time needed for bedside abdominal ultrasonography or CT examination was collected separately to evaluate the efficiency of bedside abdominal ultrasonography application. RESULTS: Bedside abdominal ultrasonography was performed in 106 patients with blunt abdominal trauma, of which 71 critical patients received surgery. The overall diagnostic accordance rate was 88.68%. The diagnostic accordance rate for liver injury, spleen injury, kidney injury, gut perforation, retroperitoneal hematoma and multiple abdominal organ injury were 100%, 94.73%, 94.12%, 20.00%, 100% and 81.48%, respectively. Among the 71 critical patients, the diagnostic accordance rate was 94.37%, in which the diagnostic accordance rate for liver injury, spleen injury, kidney injury, gut perforation and multiple abdominal organ injury were 100%, 100%, 100%, 20.00% and 100%. The mean time for imaging examination of bedside abdominal ultrasonography was longer than that for CT scan (4.45 ± 1.63 vs. 2.38 ± 1.19) min; however, the mean waiting time before examination (7.37 ± 2.01 vs. 16.42 ± 6.37) min, the time to make a diagnostic report (6.42 ± 3.35 vs. 36.26 ± 13.33) min, and the overall time (17.24 ± 2.33 vs. 55.06 ± 6.96) min were shorter for bedside abdominal ultrasonography than for CT scan. CONCLUSION: Bedside ultrasonography application provides both efficiency and reliability for the assessment of blunt abdominal trauma. Especially for patients with free peritoneal effusion and critical patients, bedside ultrasonography has been proved obvious advantageous. However, for negative bedside ultrasonography patients with blunt abdominal trauma, we recommend further abdominal CT scan or serial ultrasonography scans subsequently.

Multi-primary-color quantum-dot down-converting films for display applications.

We propose and fabricate a multi-primary-color (MPC) quantum-dot down-converting film (QDDCF). A four-primary-color QDDCF composed of red (R), yellowish green (YG), bluish green (BG), and blue (B) subpixels was fabricated via totally five rounds of photolithographic processes. A verification platform was built up using a laser projector, and the measured results show that the QD film can expand display color gamut to 118.60% of Rec. 2020 and can cover the entire Pointer's gamut. The issues of blue light absorption and film thickness are analyzed in detail. The combination of MPC technology and QDDCF is a potential strategy to realize ultra wide color gamut for emerging display technologies.

Umbilical Cord Concentrations of Selected Heavy Metals and Risk for Orofacial Clefts.

Although arsenic (As), cadmium (Cd), lead (Pb), and nickel (Ni) have the ability to induce orofacial clefts (OFCs) in rodents, evidence is absent from human epidemiological investigations with markers of in utero exposure. We investigated the associations between concentrations of As, Cd, Pb, and Ni in umbilical cord tissues and risk of OFCs, and the interactions between each pair of metals on OFC risk in a case-control study. Umbilical cord concentrations of metals were determined by inductively coupled plasma mass spectrometry in 92 OFC cases and 200 nonmalformed controls. Concentrations above the median of all subjects was associated with an elevated OFC risk of 8.36-fold for As, 7.22-fold for Cd, 15.32-fold for Pb, and 6.79-fold for Ni. Concentrations of As, Cd, Pb, and Ni were also associated with risks for OFC subtypes. When metal concentrations were divided into tertiles by levels of metal concentrations of all subjects, dose-response relationships of risks for total OFCs and subtypes with As, Cd, Pb, and Ni concentrations were demonstrated. Significant synergistic interaction between As and Ni on the risk of OFCs was also observed. Therefore, elevated in utero exposure to As, Cd, Pb, and Ni may increase the risks of OFCs in newborns.

Microalgal Oil from Schizochytrium sp. Prevents HFD-Induced Abdominal Fat Accumulation in Mice.

OBJECTIVE: Dietary n-3 polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acids (EPA) and docosahexaenoic acid (DHA), are proved to be effective in obesity reduction. Microalgal oil (MO) is an important alternative source of n-3 PUFAs that effectively alleviates obesity. The aim of the present study was to explore the anti-obesity effects of microalgal oil from Schizochytrium sp. (SMO) and to compare the effects of 2 SMOs (SMO1 and SMO2) with different levels of purity of n-3 PUFAs on high fat diet (HFD)-induced obesity in male C57BL/6J mice. METHODS: Mice were randomly divided into 5 groups: (1) regular chow (RC); (2) HFD; (3) HFD + fish oil (FO); (4) HFD + SMO1; and (5) HFD + SMO2. Body weight and food intake were weekly monitored. After 16 weeks of treatment, a glucose tolerance test (GTT) and an insulin tolerance test (ITT) were performed. Serum lipid profile, morphological changes in the liver and epididymal white adipose tissue (eWAT), and the mRNA expression of lipid metabolism-related genes were also examined. RESULTS: SMO treatment significantly decreased HFD-induced abdominal fat accumulation, lowered the levels of triglycerides, cholesterol, and low-density lipoprotein, as did the positive control treated with FO. Morphological examination revealed a remarkable reduction in lipid droplet formation in the liver tissue and the particle size of eWAT. An alleviation of inflammation infiltration in eWAT caused by a high-fat diet was also observed. Real-time reverse transcription-polymerase chain reaction analysis examination confirmed that microalgal oil inhibited the gene expression of fatty acid synthase, sterol responsive element-binding protein-1c, and acetyl-CoA carboxylase but promoted that of hormone-sensitive lipase and lipoprotein lipase, carnitine palmitoyltransferase-1, and uncoupling proteins in the liver and eWAT. Moreover, similar anti-obesity effects were obtained with the same dosage but different purity of n-3 PUFAs. CONCLUSIONS: As an alternative n-3 PUFAs resource, dietary intake of SMO might be beneficial to prevent HFD-induced abdominal fat accumulation.

Pharmacophore-Based Virtual Screening of Novel Inhibitors and Docking Analysis for CYP51A from Penicillium italicum.

Sterol 14α-demethylases from Cytochrome P450 family (CYP51s) are essential enzymes in sterol biosynthesis and well-known as the target of antifungal drugs. The 3D structure of CYP51A from Penicillium italicum (PiCYP51A) was constructed through homology modeling based on the crystal structure of human CYP51A (PDB: 3LD6). Molecular dynamics (MD) simulation was operated to relax the initial model and followed by quality assessment using PROCHECK program. On the basis of the docking information on the currently available CYP51s with the patent demethylase inhibitors (DMIs), pharmacophore-based virtual screening combined with docking analysis was performed to pick out twelve new compounds from ZINC database. Six hits revealed in the ligand database suggested potential ability to inhibit PiCYP51A. Compared to patent fungicide triazolone, the top three lead compounds had similar or higher affinity with the target enzyme, and accordingly, exhibited comparable or lower EC50 values to P. italicum isolates. The results could provide references for de novo antifungal drug design.

Theory and application of TTFields in newly diagnosed glioblastoma.

BACKGROUND: Glioblastoma is the most common primary malignant brain tumor in adults. TTFields is a therapy that use intermediate-frequency and low-intensity alternating electric fields to treat tumors. For patients with ndGBM, the addition of TTFields after the concurrent chemoradiotherapy phase of the Stupp regimen can improve prognosis. However, TTFields still has the potential to further prolong the survival of ndGBM patients. AIM: By summarizing the mechanism and application status of TTFields in the treatment of ndGBM, the application prospect of TTFields in ndbm treatment is prospected. METHODS: We review the recent literature and included 76 articles to summarize the mechanism of TTfields in the treatment of ndGBM. The current clinical application status and potential health benefits of TTFields in the treatment of ndGBM are also discussed. RESULTS: TTFields can interfere with tumor cell mitosis, lead to tumor cell apoptosis and increased autophagy, hinder DNA damage repair, induce ICD, activate tumor immune microenvironment, reduce cancer cell metastasis and invasion, and increase BBB permeability. TTFields combines with chemoradiotherapy has made progress, its optimal application time is being explored and the problems that need to be considered when retaining the electrode patches for radiotherapy are further discussed. TTFields shows potential in combination with immunotherapy, antimitotic agents, and PARP inhibitors, as well as in patients with subtentorial gliomas. CONCLUSION: This review summarizes mechanisms of TTFields in the treatment of ndGBM, and describes the current clinical application of TTFields in ndGBM. Through the understanding of its principle and application status, we believe that TTFields still has the potential to further prolong the survival of ndGBM patients. Thus,research is still needed to explore new ways to combine TTFields with other therapies and optimize the use of TTFields to realize its full potential in ndGBM patients.