Progress of engineered bacteria for tumour therapy.

Finding novel therapeutic modalities, improving drug delivery efficiency and targeting, and reducing the immune escape of tumor cells are currently hot topics in the field of tumor therapy. Bacterial therapeutics have proven highly effective in preventing tumor spread and recurrence, used alone or in combination with traditional therapies. In recent years, a growing number of researchers have significantly improved the targeting and penetration of bacteria by using genetic engineering technology, which has received widespread attention in the field of tumor therapy. In this paper, we provide an overview and assessment of the advancements made in the field of tumor therapy using genetically engineered bacteria. We cover three major aspects: the development of engineered bacteria, their integration with other therapeutic techniques, and the current state of clinical trials. Lastly, we discuss the limitations and challenges that are currently being faced in the utilization of engineered bacteria for tumor therapy.

Anisotropic Te/PdSe2 Van Der Waals Heterojunction for Self-Powered Broadband and Polarization-Sensitive Photodetection.

Polarization-sensitive broadband optoelectronic detection is crucial for future sensing, imaging, and communication technologies. Narrow bandgap 2D materials, such as Te and PdSe2, show promise for these applications, yet their polarization performance is limited by inherent structural anisotropies. In this work, a self-powered, broadband photodetector utilizing a Te/PdSe2 van der Waals (vdWs) heterojunction, with orientations meticulously tailored is introduced through polarized Raman optical spectra and tensor calculations to enhance linear polarization sensitivity. The device exhibits anisotropy ratios of 1.48 at 405 nm, 3.56 at 1550 nm, and 1.62 at 4 µm, surpassing previously-reported photodetectors based on pristine Te and PdSe2. Additionally, it exhibits high responsivity (617 mA W-1 at 1550 nm), specific detectivity (5.27 × 1010 Jones), fast response (≈4.5 µs), and an extended spectral range beyond 4 µm. The findings highlight the significance of orientation-engineered heterostructures in enhancing polarization-sensitive photodetectors and advancing optoelectronic technology.

Advances in succinic acid production: the enhancement of CO2 fixation for the carbon sequestration benefits.

Succinic acid (SA), one of the 12 top platform chemicals produced from biomass, is a precursor of various high value-added derivatives. Specially, 1 mol CO2 is assimilated in 1 mol SA biosynthetic route under anaerobic conditions, which helps to achieve carbon reduction goals. In this review, methods for enhanced CO2 fixation in SA production and utilization of waste biomass for SA production are reviewed. Bioelectrochemical and bioreactor coupling systems constructed with off-gas reutilization to capture CO2 more efficiently were highlighted. In addition, the techno-economic analysis and carbon sequestration benefits for the synthesis of bio-based SA from CO2 and waste biomass are analyzed. Finally, a droplet microfluidics-based high-throughput screening technique applied to the future bioproduction of SA is proposed as a promising approach.

Association between BMI-based metabolic phenotypes and prevalence of intracranial atherosclerotic stenosis: a cross-sectional study.

BACKGROUND: Obesity and metabolic syndrome (MetS) have been acknowledged to commonly co-exist and lead to increased risks of stroke, whereas the association between various BMI-based metabolic phenotypes and development of intracranial atherosclerotic stenosis (ICAS) remained controversial. METHODS: A total of 5355 participants were included from the Asymptomatic Polyvascular Abnormalities Community (APAC) study. Participants were categorized into six groups according to their body mass index (BMI) and MetS status. ICAS was assessed using transcranial Doppler (TCD) Ultrasonography. Logistic regression was employed to evaluate the association between BMI-based metabolic phenotypes and ICAS. RESULTS: 704 participants were diagnosed with ICAS. Compared to the metabolic healthy normal weight (MH-NW) group, the metabolic unhealthy normal weight (MUH-NW) group demonstrated a higher risk of ICAS (full-adjusted odds ratio [OR], 1.91; 95% confidence interval [CI], 1.42-2.57), while no significant association was observed in the metabolic unhealthy obesity (MUO) group (full-adjusted OR, 1.07; 95% CI, 0.70-1.65) and other metabolic healthy groups regardless of BMI. The results were consistent across gender, age, smoking, alcohol intake, and physical activity subgroups. CONCLUSION: The present study suggested that MUH-NW individuals had a significant association with increased risk of ICAS compared with MH-NW individuals.

Enhanced LRP8 expression induced by Helicobacter pylori drives gastric cancer progression by facilitating ß-Catenin nuclear translocation.

INTRODUCTION: Helicobacter pylori (H. pylori) infection has been associated with gastric carcinogenesis. However, the precise involvement of LRP8, the low-density lipoprotein receptor-related protein 8, in H. pylori pathogenesis and gastric cancer (GC) remains poorly understood. OBJECTIVES: To investigate the potential roles of LRP8 in H. pylori infection and gastric carcinogenesis. METHODS: Three-dimensional human-derived gastric organoids (hGO) and gastric cancer organoids (hGCO) were synthesized from the tissues obtained from human donors. In this work, multi-omics combined with in vivo and in vitro studies were conducted to investigate the potential involvement of LRP8 in H. pylori-induced GC. RESULTS: We found that H. pylori infection significantly upregulated the expression of LRP8 in human GC tissues, cells, organoids, and mouse gastric mucous. In particular, LRP8 exhibited a distinct enrichment in cancer stem cells (CSC). Functionally, silencing of LRP8 affected the formation and proliferation of tumor spheroids, while increased expression of LRP8 was associated with increased proliferation and stemness of GC cells and organoids. Mechanistically, LRP8 promotes the binding of E-cadherin to ß-catenin, thereby promoting nuclear translocation and transcriptional activity of ß-catenin. Furthermore, LRP8 interacts with the cytotoxin-associated gene A (CagA) to form the CagA/LRP8/ß-catenin complex. This complex further amplifies H. pylori-induced ß-catenin nuclear translocation, leading to increased transcription of inflammatory factors and CSC markers. Clinical analysis demonstrated that abnormal overexpression of LRP8 is correlated with a poor prognosis and resistance to 5-Fluorouracil in patients with GC. CONCLUSION: Our findings provide valuable information on the molecular intricacies of H. pylori-induced gastric carcinogenesis, offering potential therapeutic targets and prognostic markers for GC.

Modulation of intracortical circuits in primary motor cortex during automatic action tendencies.

Humans display automatic action tendencies toward emotional stimuli, showing faster automatic behavior (i.e., approaching a positive stimulus and avoiding a negative stimulus) than regulated behavior (i.e., avoiding a positive stimulus and approaching a negative stimulus). Previous studies have shown that the primary motor cortex is involved in the processing of automatic actions, with higher motor evoked potential amplitudes during automatic behavior elicited by single-pulse transcranial magnetic stimulation. However, it is unknown how intracortical circuits are involved with automatic action tendencies. Here, we measured short-interval intracortical inhibition and intracortical facilitation within the primary motor cortex by using paired-pulse transcranial magnetic stimulation protocols during a manikin task, which has been widely used to explore approaching and avoiding behavior. Results showed that intracortical facilitation was stronger during automatic behavior than during regulated behavior. Moreover, there was a significant negative correlation between reaction times and intracortical facilitation effect during automatic behavior: individuals with short reaction times had stronger faciliatory activity, as shown by higher intracortical facilitation. By contrast, no significant difference was found for short-interval intracortical inhibition between automatic behavior and regulated behavior. The results indicated that the intracortical facilitation circuit, mediated by excitatory glutamatergic neurons, in the primary motor cortex, plays an important role in mediating automatic action tendencies. This finding further supports the link between emotional perception and the action system.

Two-dimensional topological semimetals: an emerging candidate for terahertz detectors and on-chip integration.

The importance of terahertz (THz) detection lies in its ability to provide detailed information in a non-destructive manner, making it a valuable tool across various domains including spectroscopy, communication, and security. The ongoing development of THz detectors aims to enhance their sensitivity, resolution and integration into compact and portable devices such as handheld scanners or integrated communication chips. Generally, two-dimensional (2D) materials are considered potential candidates for device miniaturization but detecting THz radiation using 2D semiconductors is generally difficult due to the ultra-small photon energy. However, this challenge is being addressed by the advent of topological semimetals (TSM) with zero-bandgap characteristics. These semimetals offer low-energy excitations in proximity to the Dirac point, which is particularly important for applications requiring a broad detection range. Their distinctive band structures with linear energy-momentum dispersion near the Fermi level also lead to high electron mobility and low effective mass. The presence of topologically protected dissipationless conducting channels and self-powered response provides a basis for low-energy integration. In order to establish paradigms for semimetal-based THz detectors, this review initially offers an analytical summary of THz detection principles. Then, the review demonstrates the distinct design of devices, the excellent performance derived from the topological surface state and unique band structures in TSM. Finally, we outline the prospective avenues for on-chip integration of TSM-based THz detectors. We believe this review can promote further research on the new generation of THz detectors and facilitate advancements in THz imaging, spectroscopy, and communication systems.

Ketogenic therapy towards precision medicine for brain diseases.

Precision nutrition and nutrigenomics are emerging in the development of therapies for multiple diseases. The ketogenic diet (KD) is the most widely used clinical diet, providing high fat, low carbohydrate, and adequate protein. KD produces ketones and alters the metabolism of patients. Growing evidence suggests that KD has therapeutic effects in a wide range of neuronal diseases including epilepsy, neurodegeneration, cancer, and metabolic disorders. Although KD is considered to be a low-side-effect diet treatment, its therapeutic mechanism has not yet been fully elucidated. Also, its induced keto-response among different populations has not been elucidated. Understanding the ketone metabolism in health and disease is critical for the development of KD-associated therapeutics and synergistic therapy under any physiological background. Here, we review the current advances and known heterogeneity of the KD response and discuss the prospects for KD therapy from a precision nutrition perspective.

Effects of different sonication parameters of theta burst transcranial ultrasound stimulation on human motor cortex.

BACKGROUND: Theta burst TUS (tbTUS) can induce increased cortical excitability in human, but how different sonication parameters influence the effects are still unknown. OBJECTIVE: To examine how a range of sonication parameters, including acoustic intensity, pulse repetition frequency, duty cycle and sonication duration, influence the effects of tbTUS on human motor cortical excitability. METHODS: 14 right-handed healthy subjects underwent 8 sessions with different tbTUS parameters in a randomized, cross-over design on separate days. The original tbTUS protocol was studied in one session and one parameter was changed in each of the seven sessions. To examine changes in cortical excitability induced by tbTUS, we measured the motor-evoked potential (MEP) amplitude, resting motor threshold, short-interval intracortical inhibition and intracortical facilitation, as well as short-interval intracortical facilitation before and up to 90 min after tbTUS. RESULTS: All conditions increased MEP amplitudes except the condition with low acoustic intensity of 10 W/cm2. Pulse repetition frequency of 5 Hz produced higher MEP amplitudes compared to pulse repetition frequencies of 2 and 10 Hz. In addition, higher duty cycles (5%, 10%, and 15%) and longer sonication durations (40, 80, and 120 s) were associated with longer duration of increased MEP amplitudes. Resting motor threshold remained stable in all conditions. For paired-pulse TMS measures, tbTUS reduced short-interval intracortical inhibition and enhanced short-interval intracortical facilitation, but had no effect on intracortical facilitation. CONCLUSIONS: Ultrasound bursts repeated at theta (∼5 Hz) frequency is optimal to produce increased cortical excitability with the range of 2-10 Hz. Furthermore, there was a dose-response effect regarding duty cycle and sonication duration in tbTUS for plasticity induction. The aftereffects of tbTUS were associated with a shift of the inhibition/excitation balance toward less inhibition and more excitation in the motor cortex. These findings can be used to determine the optimal tbTUS parameters in neuroscience research and treatment of neurological and psychiatric disorders.

Combining directed evolution with high cell permeability for high-level cadaverine production in engineered Escherichia coli.

The biosynthesis of cadaverine from lysine is an environmentally promising technology, that could contribute to a more sustainable approach to manufacturing bio-nylon 5X. However, the titer of biosynthesized cadaverine has still not reached a sufficient level for industrial production. A powerful green cell factory was developed to enhance cadaverine production by regulating lipopolysaccharide (LPS) genes and improving membrane permeability. Firstly, 10 LPS mutant strains were constructed and the effect on the growth was investigated. Then, the lysine decarboxylase (CadA) was overexpressed in 10 LPS mutant strains of Escherichia coli MG1655 and the ability to produce cadaverine was compared. Using 20.0 g L-1 of L-lysine hydrochloride (L-lysine-HCl) as the substrate for the biotransformation reaction, Cad02 and Cad06 strains exhibited high production levels of cadaverine, with 8.95 g L-1 and 7.55 g L-1 respectively while the control strain Cad00 only 4.92 g L-1 . Directed evolution of CadA was also used to improve its stability under alkaline conditions. The cadaverine production of the Cad02-M mutant stain increased by 1.86 times at pH 8.0. Finally, the production process was scaled up using recombinant whole cells as catalysts, achieving a high titer of 211 g L-1 cadaverine (96.8%) by fed-batch bioconversion. This study demonstrates the potential role of LPS in enhancing the efficiency of mass transfer between substrate and enzymes in vivo by increasing cell permeability. The results indicate that the argumentation of cell permeability could not only significantly enhance the biotransformation efficiency of cadaverine, but also provide a universally applicable, straightforward, environment-friendly, and cost-effective method for the biosynthesis of other high-value chemicals.

Efficacy of ginkgo diterpene lactone meglumine on cognitive function in patients with acute ischemic stroke: a predefined exploratory analysis of a multicenter, double-blind, randomized controlled trial.

BACKGROUND: Ginkgo diterpene lactone meglumine (GDLM) could improve the functional outcome in patients with acute ischemic stroke (AIS). This study aimed to investigate the efficacy of GDLM on cognitive function in patients with AIS. METHODS: This is a predefined exploratory analysis of the Efficacy and Safety of Ginkgo Diterpene Lactone Meglumine in Acute Ischemic Stroke trial, which was primarily designed to investigate the efficacy and safety of GDLM versus placebo on functional outcome at 100 centers in China. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) test. The primary outcomes were changes of MoCA from baseline to Day 14 and Day 90 after randomization. RESULTS: A total of 3163 patients with completed data on MoCA were enrolled. There was statistically significant difference of changes in MoCA scores between the GDLM group and the placebo group from baseline to Day 14 (mean difference, 0.31; 95% confidence interval [CI], 0.08-0.53; P = 0.007) and to Day 90 after randomization (mean difference, 0.47; 95% CI, 0.22-0.72; P < 0.001). Additionally, GDLM was associated with a higher proportion of patients who reached a clinically significant level of improvement in MoCA from baseline to Day 14 (odds ratio [OR], 1.25; 95% CI, 1.08-1.44; P = 0.002) and Day 90 after randomization (OR, 1.21; 95% CI, 1.03-1.41; P = 0.02). Specially, GDLM could significantly improve the scores of visuo-spatial and executive function and language. CONCLUSIONS: In this predefined analysis of patients with AIS, GDLM could improve the 14-day and 90-day cognitive function compared with the placebo.

Lipid-mediated protein corona regulation with increased apolipoprotein A-I recruitment for glioma targeting.

Protein corona has long been a source of concern, as it might impair the targeting efficacy of targeted drug delivery systems. However, engineered up-regulating the adsorption of certain functional serum proteins could provide nanoparticles with specific targeting drug delivery capacity. Herein, apolipoprotein A-I absorption increased nanoparticles (SPC-PLGA NPs), composed with the Food and Drug Administration approved intravenously injectable soybean phosphatidylcholine (SPC) and poly (DL-lactide-co-glycolide) (PLGA), were fabricated for enhanced glioma targeting. Due to the high affinity of SPC and apolipoprotein A-I, the percentage of apolipoprotein A-I in the protein corona of SPC-PLGA NPs was 2.19-fold higher than that of nanoparticles without SPC, which made SPC-PLGA NPs have superior glioma targeting ability through binding to scavenger receptor class BI on blood-brain barrier and glioma cells both in vitro and in vivo. SPC-PLGA NPs loaded with paclitaxel could effectively reduce glioma invasion and prolong the survival time of glioma-bearing mice. In conclusion, we provided a good example of the direction of achieving targeting drug delivery based on protein corona regulation.

Environmental exposure to per- and polyfluoroalkyl substances mixture and asthma in adolescents.

BACKGROUND: Previous epidemiological studies about the relationship between per- and polyfluoroalkyl substances (PFAS) concentrations and adolescent asthma have typically examined single PFAS, without considering the mixtures effects of PFAS. METHODS: Using data from the 2013-2018 National Health and Nutrition Examination Survey (NHANES), 886 adolescents aged 12-19 years were included in this study. We explored the association between PFAS mixture concentrations and adolescent asthma using weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models, respectively. RESULTS: After adjusting for confounders, the results of the WQS regression and BKMR models were consistent, with mixed exposure to the five PFAS not significantly associated with asthma in all adolescents. The association remained nonsignificant in the subgroup analysis by sex. CONCLUSIONS: Our study demonstrated no significant association between mixed exposure to PFAS and adolescent asthma, and more large cohort studies are needed to confirm this in the future.

Association and pathways of baseline and longitudinal hemoglobin A1c with the risk of incident stroke: A nationwide prospective cohort study.

AIMS: To investigate the association of baseline and long-term mean hemoglobin A1c (HbA1c) with the risk of stroke. METHODS: A total of 11,220 participants aged over 45 years and without stroke at baseline were enrolled from the China Health and Retirement Longitudinal Study. Mean HbA1c was calculated as the mean of HbA1c at all previous visits before stroke occurred or the end of follow-up. Multivariable-adjusted Cox regressions and Bayesian network were used for the analysis. RESULTS: During a median follow-up of 7.50 years, a total of 626 cases of stroke occurred. The risk of stroke increased with quintiles of baseline and mean HbA1c, the hazard ratio (HR) in Q5 versus Q1 was 1.30 (95 % confidence interval [CI],1.03-1.64) and 1.79 (95 % CI, 1.38-2.34), respectively. Per 1 unit increase in baseline and mean HbA1c was associated with 10 % (HR, 1.10; 95 % CI, 1.02-1.18) an 12 % (HR, 1.12; 95 % CI, 1.05-1.19) higher risk of stroke. Bayesian network analysis showed that the pathway from HbA1c to stroke was through hypertension, dyslipidemia, obesity, and inflammation. CONCLUSIONS: Elevated levels of both baseline and long-term HbA1c were associated with increased risk of stroke, and hypertension and obesity played an important role in the pathway.

Inhibiting autophagy enhanced mitotic catastrophe-mediated anticancer immune responses by regulating the cGAS-STING pathway.

Given the limitations of the response rate and efficacy of immune checkpoint inhibitors (ICIs) in clinical applications, exploring new therapeutic strategies for cancer immunotherapy is necessary. We found that 5-(3,4,5-trimethoxybenzoyl)-4-methyl-2-(p-tolyl)imidazole (BZML), a microtubule-targeting agent, exhibited potent anticancer activity by inducing mitotic catastrophe in A549/Taxol and L929 cells. Nuclear membrane disruption and nuclease reduction provided favorable conditions for cGAS-STING pathway activation in cells with mitotic catastrophe. Similar results were obtained in paclitaxel-, docetaxel- and doxorubicin-induced mitotic catastrophe in various cancer cells. Notably, the surface localization of CALR and MHC-I and the release of HMGB1 were also significantly increased in cells with mitotic catastrophe, but not in apoptotic cells, suggesting that mitotic catastrophe is an immunogenic cell death. Furthermore, activated CD8+T cells enhanced the anticancer effects originating from mitotic catastrophe induced by BZML. Inhibiting the cGAS-STING pathway failed to affect BZML-induced mitotic catastrophe but could inhibit mitotic catastrophe-mediated anticancer immune effects. Interestingly, the expression of p-TBK1 first increased and then declined; however, autophagy inhibition reversed the decrease in p-TBK1 expression and enhanced mitotic catastrophe-mediated anticancer immune effects. Collectively, the inhibition of autophagy can potentiate mitotic catastrophe-mediated anticancer immune effects by regulating the cGAS-STING pathway, which explains why the anticancer immune effects induced by chemotherapeutics have not fully exerted their therapeutic efficacy in some patients and opens a new area of research in cancer immunotherapy.

Sublingual Edaravone Dexborneol for the Treatment of Acute Ischemic Stroke: The TASTE-SL Randomized Clinical Trial.

Importance: Sublingual edaravone dexborneol, which can rapidly diffuse and be absorbed through the oral mucosa after sublingual exposure, is a multitarget brain cytoprotection composed of antioxidant and anti-inflammatory ingredients edaravone and dexborneol. Objective: To investigate the efficacy and safety of sublingual edaravone dexborneol on 90-day functional outcome in patients with acute ischemic stroke (AIS). Design, Setting, and Participants: This was a double-blind, placebo-controlled, multicenter, parallel-group, phase 3 randomized clinical trial conducted from June 28, 2021, to August 10, 2022, with 90-day follow-up. Participants were recruited from 33 centers in China. Patients randomly assigned to treatment groups were aged 18 to 80 years and had a National Institutes of Health Stroke Scale score between 6 and 20, a total motor deficit score of the upper and lower limbs of 2 or greater, a clinically diagnosed AIS symptom within 48 hours, and a modified Rankin Scale (mRS) score of 1 or less before stroke. Patients who did not meet the eligibility criteria or declined to participate were excluded. Intervention: Patients were assigned, in a 1:1 ratio, to receive sublingual edaravone dexborneol (edaravone, 30 mg; dexborneol, 6 mg) or placebo (edaravone, 0 mg; dexborneol, 60 µg) twice daily for 14 days and were followed up until 90 days. Main Outcomes and Measures: The primary efficacy outcome was the proportion of patients with mRS score of 1 or less on day 90 after randomization. Results: Of 956 patients, 42 were excluded. A total of 914 patients (median [IQR] age, 64.0 [56.0-70.0] years; 608 male [66.5%]) were randomly allocated to the edaravone dexborneol group (450 [49.2%]) or placebo group (464 [50.8%]). The edaravone dexborneol group showed a significantly higher proportion of patients experiencing good functional outcomes on day 90 after randomization compared with the placebo group (290 [64.4%] vs 254 [54.7%]; risk difference, 9.70%; 95% CI, 3.37%-16.03%; odds ratio, 1.50; 95% CI, 1.15-1.95, P = .003). The rate of adverse events was similar between the 2 groups (89.8% [405 of 450] vs 90.1% [418 of 464]). Conclusion and Relevance: Among patients with AIS within 48 hours, sublingual edaravone dexborneol could improve the proportion of those achieving a favorable functional outcome at 90 days compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT04950920.

Systemic Immune-Inflammation Response is Associated with Futile Recanalization After Endovascular Treatment.

BACKGROUND: Frequent incidence of futile recanalization decreases the benefit of endovascular treatment (EVT) in acute ischemic stroke. We hypothesized that the inflammation and immune response after ischemic are associated with futile recanalization. We aimed to investigate the correlation of admission systemic immune-inflammation index (SII) with futile recanalization post EVT. METHODS: Patients with successful recanalization (modified Thrombolysis in Cerebral Ischemia angiographic score 2b-3) and maintained artery recanalized after 24 h of EVT were chosen from a prospective nationwide registry study. Futile recanalization was defined as a poor functional outcome (modified Rankin Scale score 3-6) at 90 days, irrespective of a successful recanalization. At admission, SII was calculated as (platelet count × neutrophil count)/lymphocyte count/100. Logistic regression analysis helped to test the relationship of SII with futile recanalization. RESULTS: Among the 1,002 patients included, futile recanalization occurred in 508 (50.70%). No matter whether tested as quartiles or continuous variables, SII was significantly associated with futile recanalization (P < 0.05), and for every one standard deviation increase of SII, the risk of futile recanalization elevated by 22.3% (odds ratio 1.223, 95% confidence interval 1.053-1.444, P = 0.0093). Moreover, no significant interactions could be observed between SII or SII quartiles and age, baseline National Institutes of Health Stroke Scale scores, onset-to-recanalization time, and modified Thrombolysis in Cerebral Ischemia angiographic scores (all P for interaction > 0.05). CONCLUSIONS: Early SII elevation was associated with an increased risk of futile recanalization among patients with EVT. Our results indicated that therapeutic drug targeting hyperreactive immune-inflammation response might be helpful for reducing the incidence of futile recanalization.

A gene cluster encoding a nonribosomal peptide synthetase-like enzyme catalyzes γ-aromatic butenolides.

Sea cucumber-derived fungi have attracted much attention due to their capacity to produce an incredible variety of secondary metabolites. Genome-wide information on Aspergillus micronesiensis H39 obtained using third-generation sequencing technology (PacBio-SMRT) showed that the strain contains nonribosomal peptide synthetase (NRPS)-like gene clusters, which aroused our interest in mining its secondary metabolites. 11 known compounds (1-11), including two γ-aromatic butenolides (γ-AB) and five cytochalasans, were isolated from A. micronesiensis H39. The structures of the compounds were determined by NMR and ESIMS, and comparison with those reported in the literature. From the perspective of biogenetic origins, the γ-butyrolactone core of compounds 1 and 2 was assembled by NRPS-like enzyme. All of the obtained compounds showed no inhibitory activity against drug-resistant bacteria and fungi, as well as compounds 1 and 2 had no anti-angiogenic activity against zebrafish.

Low-Density Lipoprotein Cholesterol to Triglyceride Ratio and Clinical Outcomes after Acute Ischaemic Stroke or Transient Ischaemic Attack.

AIMS: Studies showed that low-density lipoprotein cholesterol (LDL-C) to triglyceride (TG) ratio could be used as a predictive parameter of low-density lipoprotein oxidation in vivo and the level of small dense LDL-C. However, whether LDL-C/TG ratio is associated with stroke prognosis remains unclear. We investigated the associations of LDL-C/TG ratio with outcomes in patients with acute ischaemic stroke (AIS) or transient ischaemic attacks (TIA) and explored whether it produced more predictive value than LDL-C and TG. METHODS: Data were derived from the Third China National Stroke Registry (CNSR-III). Multivariable Cox regression for stroke recurrence, composite vascular events and all-cause death and logistic regression for the poor functional outcome (modified Rankin Scale score 3-6) were used. RESULTS: A total of 14123 patients were included. After adjusting for confounding factors, quartile 4 of LDL-C/TG ratio was associated with an increased risk of recurrent stroke (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.03-1.56), composite vascular events (HR,1.23; 95% CI, 1.00-1.52), death (HR,1.70; 95% CI, 1.13-2.54) and poor functional outcome (odds ratio, 1.34; 95% CI, 1.12-1.61) at 3 months follow-up compared with quartile 1. We also found that quartile 4 of LDL-C and TG was positively and negatively associated with poor functional outcome at 3 months, respectively. LDL-C/TG ratio performed better than LDL-C or TG in predicting clinical outcomes. CONCLUSIONS: LDL-C/TG ratio was associated with the risk of stroke recurrence, composite vascular events, death and poor functional outcome in patients with AIS or TIA.

Stability analysis of pumped storage hydropower plant in abandoned open-pit mine affected by dynamic surface subsidence of combined mining.

The construction of a pumped storage hydropower plant (PSHP) in an abandoned open-pit mine is a potential alternative to green mining and energy storage, which can increase the utilization rate of renewable energy and develop residual resources of abandoned mines. Dynamic surface subsidence affected by combined underground and open-pit mining (CUOPM) seriously affects the construction and operation of the PSHP and is one of the critical scientific issues that needs to be solved immediately. The stability of the PSHP was analyzed and treatment scheme of the goafs was proposed based on on-site measurement, theoretical analysis, and numerical simulation. First, the distribution of goafs in the Haizhou open-pit mining area was investigated and surface subsidence value was obtained using InSAR technology and ground monitoring. Secondly, the surface subsidence mechanism affected by CUOPM is analyzed and indicates the subsidence maximum values and scope of influence are greater than those of single underground mining. A dynamic surface subsidence prediction model for combined mining is established based on the Knothe time function model. Thirdly, based on the CVISC model, the numerical calculation models were established by using FLAC3D, and the characteristics and laws of surface subsidence in different periods of CUOPM were studied. The comparative analysis of the observation results shows that the proposed model and numerical simulation calculation method have excellent applicability and accuracy. Finally, a stability evaluation method of PSHP was established, and the results of the evaluation show that the affected areas are the semi-ground powerhouse (SGPH) and the west side of the lower reservoir. The method of grouting filling was used to treat the goafs, and the results showed that it effectively alleviates the dynamic surface subsidence affected by CUOPM, and provides a safety guarantee for PSHP.