Measurement of Zinc Ions in Seawater Samples Using a Microfluidic System Based on the GR/CeO2/Nafion Material.

Considering that heavy-metal contamination of seawater is getting worse, building a quick, accurate and portable device for detecting trace zinc in seawater in real time would be very beneficial. In this work, a microfluidic system was developed that includes a planar disc electrode, a micro-cavity for detection, an electrochemical workstation, a computer, a container for waste liquid reprocessing, an external pipeline and other components as well as a graphene/cerium oxide/nano-cerium oxide/Nafion composite membrane was used to modify the planar disc electrode (GR/CeO2/Nafion/Au) to investigate the electrochemical behaviour of Zn(II) using cyclic voltammetry, square-wave voltammetry and orthogonal test methods. Under optimal experimental conditions, the peak reaction current of Zn(II) showed a good linear relationship with the concentration of Zn(II) in the range of 1-900 µg/L with a correlation coefficient of 0.998, and the detection limit of the method was 0.87 µg/L. In addition, the microfluidic system had good stability, reproducibility and anti-interference. The system was used for determining zinc ions in real seawater samples, and the results were very similar to those of inductively coupled plasma-emission spectrometry, demonstrating the practicality of the system for the detection of trace zinc.

Optimizing multicopy chromosomal integration for stable high-performing strains.

The copy number of genes in chromosomes can be modified by chromosomal integration to construct efficient microbial cell factories but the resulting genetic systems are prone to failure or instability from triggering homologous recombination in repetitive DNA sequences. Finding the optimal copy number of each gene in a pathway is also time and labor intensive. To overcome these challenges, we applied a multiple nonrepetitive coding sequence calculator that generates sets of coding DNA sequence (CDS) variants. A machine learning method was developed to calculate the optimal copy number combination of genes in a pathway. We obtained an engineered Yarrowia lipolytica strain for eicosapentaenoic acid biosynthesis in 6 months, producing the highest titer of 27.5 g l-1 in a 50-liter bioreactor. Moreover, the lycopene production in Escherichia coli was also greatly improved. Importantly, all engineered strains of Y. lipolytica, E. coli and Saccharomyces cerevisiae constructed with nonrepetitive CDSs maintained genetic stability.

Lactylation of NAT10 promotes N4-acetylcytidine modification on tRNASer-CGA-1-1 to boost oncogenic DNA virus KSHV reactivation.

N4-acetylcytidine (ac4C), a conserved but recently rediscovered RNA modification on tRNAs, rRNAs and mRNAs, is catalyzed by N-acetyltransferase 10 (NAT10). Lysine acylation is a ubiquitous protein modification that controls protein functions. Our latest study demonstrates a NAT10-dependent ac4C modification, which occurs on the polyadenylated nuclear RNA (PAN) encoded by oncogenic DNA virus Kaposi's sarcoma-associated herpesvirus (KSHV), can induce KSHV reactivation from latency and activate inflammasome. However, it remains unclear whether a novel lysine acylation occurs in NAT10 during KSHV reactivation and how this acylation of NAT10 regulates tRNAs ac4C modification. Here, we showed that NAT10 was lactylated by α-tubulin acetyltransferase 1 (ATAT1), as a writer at the critical domain, to exert RNA acetyltransferase function and thus increase the ac4C level of tRNASer-CGA-1-1. Mutagenesis at the ac4C site in tRNASer-CGA-1-1 inhibited its ac4C modifications, translation efficiency of viral lytic genes, and virion production. Mechanistically, KSHV PAN orchestrated NAT10 and ATAT1 to enhance NAT10 lactylation, resulting in tRNASer-CGA-1-1 ac4C modification, eventually boosting KSHV reactivation. Our findings reveal a novel post-translational modification in NAT10, as well as expand the understanding about tRNA-related ac4C modification during KSHV replication, which may be exploited to design therapeutic strategies for KSHV-related diseases.

Pooled CRISPR Interference Screening Identifies Crucial Transcription Factors in Gas-Fermenting Clostridium ljungdahlii.

Gas-fermenting Clostridium species hold tremendous promise for one-carbon biomanufacturing. To unlock their full potential, it is crucial to unravel and optimize the intricate regulatory networks that govern these organisms; however, this aspect is currently underexplored. In this study, we employed pooled CRISPR interference (CRISPRi) screening to uncover a wide range of functional transcription factors (TFs) in Clostridium ljungdahlii, a representative species of gas-fermenting Clostridium, with a special focus on TFs associated with the utilization of carbon resources. Among the 425 TF candidates, we identified 75 and 68 TF genes affecting the heterotrophic and autotrophic growth of C. ljungdahlii, respectively. We focused our attention on two of the screened TFs, NrdR and DeoR, and revealed their pivotal roles in the regulation of deoxyribonucleoside triphosphates (dNTPs) supply, carbon fixation, and product synthesis in C. ljungdahlii, thereby influencing the strain performance in gas fermentation. Based on this, we proceeded to optimize the expression of deoR in C. ljungdahlii by adjusting its promoter strength, leading to an improved growth rate and ethanol synthesis of C. ljungdahlii when utilizing syngas. This study highlights the effectiveness of pooled CRISPRi screening in gas-fermenting Clostridium species, expanding the horizons for functional genomic research in these industrially important bacteria.

Oxidative stress contributes to hypermethylation of Histone H3 lysine 9 in placental trophoblasts from preeclamptic pregnancies.

Background and objective: Aberrant epigenetic regulation and increased oxidative stress in the placenta play a significant role in placental pathophysiology and fetal programming in preeclampsia, a hypertensive disorder in human pregnancy. The purpose of the study is to investigate if hypermethylation of histone H3K9 occurs in placental trophoblasts from preeclampsia. Methods: Trophoblasts were isolated and cultured from 14 placentas, 7 from normotensive pregnant women and 7 from preeclamptic pregnancies. Methylated H3K9 expression and antioxidant superoxide dismutase expression were determined by Western blot. We also examined consequences of oxidative stress and the downstream effects of histone methyltransferase inhibition on H3K9 expression associated with antioxidant CuZn-SOD and Mn-SOD expression in placental trophoblasts. Results: We found that expression of mono-, di-, and tri-methylation of histone H3 lysine 9 (H3K9me1, H3K9me2 and H3K9me3) was significantly increased, p<0.01, which correlated with downregulation of antioxidant superoxide dismutase CuZn-SOD and Mn-SOD expression, in trophoblasts from preeclamptic placentas compared to those from uncomplicated control placentas. We further demonstrated hypoxia could promote histone H3K9 methylation in placental trophoblasts, and hypoxia-induced upregulation of H3K9me1, H3K9me2 and H3K9me3 expression was reversible when hypoxic condition was removed. In addition, we also uncovered that inhibition of methyltransferase not only prevented hypoxia-induced upregulation of H3K9me1, H3K9me2 and H3K9me3 expression, but also abolished hypoxia-induced downregulation of CuZn-SOD and Mn-SOD expression in placental trophoblasts. Conclusions: These findings are noteworthy and provide further evidence that increased oxidative stress in the intrauterine environment is likely a mechanism to induce aberrant histone modification in placental trophoblasts in preeclampsia. Moreover, CuZn-SOD and Mn-SOD expression/activity are possibly H3K9 methylation-dependent in placental trophoblasts, which further suggest that oxidative stress and aberrant histone modification have significant impact on placental trophoblasts/fetal programming in preeclampsia.

Uniportal video-assisted thoracic surgery versus open thoracotomy for chronic pain after surgery: a prospective cohort study.

PURPOSE: The potential of uniportal video-assisted thoracic surgery (U-VATS) to reduce chronic pain after thoracic surgery (CPTS) compared to open thoracotomy (OT) remains unexplored. This prospective study aims to assess the incidence of CPTS following U-VATS or OT and identify associated risk factors. METHODS: Patients undergoing thoracic surgery were recruited from March 2021 to March 2022, categorized by surgical approach (U-VATS vs. OT). Standard clinical protocols for surgery, anesthesia, and analgesia were followed. Pain symptoms were assessed using the Short-form McGill Pain Questionnaire, with follow-ups up to 6 months. Perioperative factors influencing CPTS at 3 months were analyzed through univariate and multivariate methods. RESULTS: A total of 694 patients were analyzed. Acute pain after thoracic surgery (APTS) was significantly less severe in the U-VATS group (p < 0.001). U-VATS patients exhibited a lower incidence of CPTS at 3 months (63.4% vs. 80.1%, p < 0.001), with reduced severity among those experiencing CPTS (p = 0.007) and a decreased occurrence of neuropathic pain (p = 0.014). Multivariate analysis identified OT incision, moderate to severe APTS (excluding moderate static pain at 24 h postoperative), nocturnal surgery, and lung surgery as risk factors for CPTS. CONCLUSION: This study underscores the potential of U-VATS to reduce both the incidence and severity of CPTS at 3 months compared to OT. Furthermore, it highlights risk factors for CPTS, including OT incision, inadequately managed APTS, lung surgery, and nocturnal surgery. These findings emphasize the importance of considering surgical approach and perioperative pain management strategies to mitigate the burden of CPTS.

Advances and perspectives in genetic expression and operation for the oleaginous yeast Yarrowia lipolytica.

The utilization of industrial biomanufacturing has emerged as a viable and sustainable alternative to fossil-based resources for producing functional chemicals. Moreover, advancements in synthetic biology have created new opportunities for the development of innovative cell factories. Notably, Yarrowia lipolytica, an oleaginous yeast that is generally regarded as safe, possesses several advantageous characteristics, including the ability to utilize inexpensive renewable carbon sources, well-established genetic backgrounds, and mature genetic manipulation methods. Consequently, there is increasing interest in manipulating the metabolism of this yeast to enhance its potential as a biomanufacturing platform. Here, we reviewed the latest developments in genetic expression strategies and manipulation tools related to Y. lipolytica, particularly focusing on gene expression, chromosomal operation, CRISPR-based tool, and dynamic biosensors. The purpose of this review is to serve as a valuable reference for those interested in the development of a Y. lipolytica microbial factory.

Relationships between sarcopenia, depressive symptoms, and the risk of cardiovascular disease in Chinese population.

BACKGROUND: Previous studies had indicated that sarcopenia and depressive symptoms were associated with increased risk of cardiovascular disease (CVD). The aim of present study was to evaluate the combined effect of sarcopenia and depressive symptoms on the CVD risk. METHODS: A total of 11,011 participants from the China Health and Retirement Longitudinal Study 2011-2020 were included. Multivariate Cox proportional hazards regression model was used to explore the associations between sarcopenia, depressive symptoms and new-onset CVD, stroke and cardiac events. RESULTS: During the 7-year follow-up, a total of 2,388 respondents experienced CVD (including 812 stroke and 1,831 cardiac events). There is a significant additive and multiplicative interactions of sarcopenia and depressive symptoms on risk of CVD, stroke and cardiac events. Compared with those without sarcopenia and depressive symptoms, individuals with depressive sarcopenia had the highest risk of CVD, stroke and cardiac events, with the corresponding hazard ratios (95% confidence interval) were 1.43 (1.26-1.63), 1.45 (1.15-1.82) and 1.50 (1.29-1.74), respectively. CONCLUSION: Our study indicated that there was a combined effect of sarcopenia and depressive symptoms on the risk of CVD, stroke and cardiac events. Our findings highlighted the importance of identifying sarcopenia and depressive symptoms, and intervening much earlier both in older and younger population.

Study on the Effect of Microstructure and Inclusions on Corrosion Resistance of Low-N 25Cr-Type Duplex Stainless Steel via Additive Manufacturing.

Duplex stainless steels are widely used in many fields due to their excellent corrosion resistance and mechanical properties. However, it is a challenge to achieve duplex microstructure and excellent properties through additive manufacturing. In this work, a 0.09% N 25Cr-type duplex stainless steel was prepared by additive manufacturing (AM) and heat treatment, and its corrosion resistance was investigated. The results show that, compared with S32750 duplex stainless steel prepared by a conventional process, the combination value of film resistance and charge transfer resistance of AM duplex stainless steel was increased by 3.2-5.5 times and the pitting potential was increased by more than 100 mV. The disappearance of residual thermal stress and the reasonable distribution of Cr and N elements in the two phases are the reasons for the improvement of the corrosion resistance of AM duplex stainless steel after heat treatment. In addition, the extremely high purity of AM duplex stainless steel with no visible inclusions resulted in a higher corrosion resistance exhibited at lower pitting-resistance-equivalent number values.

Cortistatin protects against septic cardiomyopathy by inhibiting cardiomyocyte pyroptosis through the SSTR2-AMPK-NLRP3 pathway.

BACKGROUND: Although the pathophysiological mechanism of septic cardiomyopathy has been continuously discovered, it is still a lack of effective treatment method. Cortistatin (CST), a neuroendocrine polypeptide of the somatostatin family, has emerged as a novel cardiovascular-protective peptide, but the specific mechanism has not been elucidated. PURPOSE: The aim of our study is to explore the role of CST in cardiomyocytes pyroptosis and myocardial injury in sepsis and whether CST inhibits cardiomyocytes pyroptosis through specific binding with somastatin receptor 2 (SSTR2) and activating AMPK/Drp1 signaling pathway. METHODS AND RESULTS: In this study, plasma CST levels were significantly high and were negatively correlated with N-terminal pro-B type natriuretic peptide (NT-proBNP), a biomarker for cardiac dysfunction, in patients with sepsis. Exogenous administration of CST significantly improved survival rate and cardiac function in mouse models of sepsis by inhibiting the activation of the NLRP3 inflammasome and pyroptosis of cardiomyocytes (decreased cleavage of caspase-1, IL-1ß and gasdermin D). Pharmacological inhibition and genetic ablation revealed that CST exerted anti-pyroptosis effects by specifically binding to somatostatin receptor subtype 2 (SSTR2), thus activating AMPK and inactivating Drp1 to inhibit mitochondrial fission in cardiomyocytes. CONCLUSIONS: This study is the first to report that CST attenuates septic cardiomyopathy by inhibiting cardiomyocyte pyroptosis through the SSTR2-AMPK-Drp1-NLRP3 pathway. Importantly, CST specifically binds to SSTR2, which promotes AMPK phosphorylation, inhibits Drp1-mediated mitochondrial fission, and reduces ROS levels, thereby inhibiting NLRP3 inflammasome activation-mediated pyroptosis and alleviating sepsis-induced myocardial injury.

A causal association between amyotrophic lateral sclerosis and atrial fibrillation: a two-sample Mendelian randomization study.

Objectives: To look into the connection between amyotrophic lateral sclerosis (ALS) and atrial fibrillation (AF) using Mendelian randomization (MR). Methods: Two-sample MR was performed using genetic information from genome-wide association studies (GWAS). Genetic variants robustly associated with ALS and AF were used as instrumental variables. GWAS genetic data for ALS (n = 138,086, ncase = 27,205) and AF (n = 1,030,836, ncase = 60,620), publicly available from IEU Open. The specific MR protocols were Inverse variance-weighted (IVW), Simple mode, MR Egger, Weighted mode, and Weight median estimator (WME). Subsequently, the MR-Egger intercept and Cochran Q examine were used to evaluate instrumental variables (IVs)' heterogeneity and multiplicative effects (IVs). In addition, MR-PRESSO analysis was conducted to exclude any potential pleiotropy. Results: The IVW method demonstrated that ALS positively affected AF [OR: 1.062, 95% CI (1.004-1.122); P = 0.035]. Indeed, other MR methods were in accordance with the tendency of the IVW method (all OR > 1), and sensitivity testing verified the reliability of this MR result. Conclusions: This MR study proves a positive causal connection between ALS and atrial fibrillation. Further studies are warranted to elucidate the mechanisms linking ALS and AF.

A liquid biopsy assay for the noninvasive detection of lymph node metastases in T1 lung adenocarcinoma.

INTRODUCTION: Lung adenocarcinoma (LUAD) is a common pathological type of lung cancer. The presence of lymph node metastasis plays a crucial role in determining the overall treatment approach and long-term prognosis for early LUAD, therefore accurate prediction of lymph node metastasis is essential to guide treatment decisions and ultimately improve patient outcomes. METHODS: We performed transcriptome sequencing on T1 LUAD patients with positive or negative lymph node metastases and combined this data with The Cancer Genome Atlas Program cohort to identify potential risk molecules at the tissue level. Subsequently, by detecting the expression of these risk molecules by real-time quantitative PCR in serum samples, we developed a model to predict the risk of lymph node metastasis from a training cohort of 96 patients and a validation cohort of 158 patients. RESULTS: Through transcriptome sequencing analysis of tissue samples, we identified 11 RNA (miR-412, miR-219, miR-371, FOXC1, ID1, MMP13, COL11A1, PODXL2, CXCL13, SPOCK1 and MECOM) associated with positive lymph node metastases in T1 LUAD. As the expression of FOXC1 and COL11A1 was not detected in serum, we constructed a predictive model that accurately identifies patients with positive lymph node metastases using the remaining nine RNA molecules in the serum of T1 LUAD patients. In the training set, the model achieved an area under the curve (AUC) of 0.89, and in the validation set, the AUC was 0.91. CONCLUSIONS: We have established a new risk prediction model using serum samples from T1 LUAD patients, enabling noninvasive identification of those with positive lymph node metastases.

Causal roles of gut microbiota in cholangiocarcinoma etiology suggested by genetic study.

BACKGROUND: Cholangiocarcinoma (CCA) is a highly malignant biliary tract cancer with poor prognosis. Previous studies have implicated the gut microbiota in CCA, but evidence for causal mechanisms is lacking. AIM: To investigate the causal relationship between gut microbiota and CCA risk. METHODS: We performed a two-sample mendelian randomization study to evaluate potential causal associations between gut microbiota and CCA risk using genome-wide association study summary statistics for 196 gut microbial taxa and CCA. Genetic variants were used as instrumental variables. Multiple sensitivity analyses assessed result robustness. RESULTS: Fifteen gut microbial taxa showed significant causal associations with CCA risk. Higher genetically predicted abundance of genus Eubacteriumnodatum group, genus Ruminococcustorques group, genus Coprococcus, genus Dorea, and phylum Actinobacteria were associated with reduced risk of gallbladder cancer and extrahepatic CCA. Increased intrahepatic CCA risk was associated with higher abundance of family Veillonellaceae, genus Alistipes, order Enterobacteriales, and phylum Firmicutes. Protective effects against CCA were suggested for genus Collinsella, genus Eisenbergiella, genus Anaerostipes, genus Paraprevotella, genus Parasutterella, and phylum Verrucomicrobia. Sensitivity analyses indicated these findings were reliable without pleiotropy. CONCLUSION: This pioneering study provides novel evidence that specific gut microbiota may play causal roles in CCA risk. Further experimental validation of these candidate microbes is warranted to consolidate causality and mechanisms.

The damage mechanism in copper studied using in situ TEM nanoindentation.

Copper (Cu) has a soft-plastic nature, which makes it susceptible to damages from scratching or abrasive machining, such as lapping and polishing. It is a challenge to control these damages as the damage mechanism is elusive. Nonetheless, controlling damages is essential, especially on the atomic surfaces of Cu. To interpret the damage mechanism, in situ transmission electron microscopy (TEM) nanoindentation was performed using a cube-corner indenter with a radius of 57 nm at a loading speed of 5 nm s-1. Experimental results showed that damages originate from dislocations, evolve to stack faults, and then form broken crystallites. When the indentation depth was 45 nm at a load of 20 µN, damages comprised dislocations and stacking faults. After increasing the depth to 67 nm and load to 30 µN, the formation of broken crystallites initiated; and the critical depth was 67 nm. To validate the damage mechanism, fixed-abrasive lapping, mechanical polishing, and chemical mechanical polishing (CMP) were conducted. Firstly, a novel green CMP slurry containing silica, hydrogen peroxide, and aspartic acid was developed. After CMP, a surface roughness Ra of 0.2 nm was achieved with a scanning area of 50 µm × 50 µm; and the thickness of the damaged layer was 3.1 nm, which included a few micro-stacking faults. Lapping and mechanical polishing were carried out using a silicon carbide plate and cerium slurry, with surface roughness Ra values of 16.42 and 1.74 nm, respectively. The damaged layer of the former with a thickness of 300 nm comprised broken crystallites, dislocations, and stacking faults and that of the latter with a thickness of 33 nm involved several stacking faults. This verifies that the damage mechanism derived from in situ TEM nanoindentation is in agreement with lapping and polishing. These outcomes propose new insights into understanding the origin of damages and controlling them, as well as obtaining atomic surfaces using a novel green CMP technique for soft-plastic metals.

Sequencing and Analysis of the Complete Mitochondrial Genome of Lentipes ikeae.

We sequenced and analyzed the complete mitochondrial genome of Lentipes ikeae and explored the phylogenetic relationships among Sicydiinae based on mitochondrial genome sequences. The complete mitochondrial genome sequence of L. ikeae was determined using the Illumina HiSeq X Ten sequencing platform, and the gene structural characteristics and base composition were analyzed. Based on the mitochondrial genome sequences of 28 Sicydiinae species published in GenBank and mitochondrial protein-coding genes (PCGs), Acanthogobius flavimanus (Gobionellinae) was selected as an outgroup to construct phylogenetic trees of Sicydiinae using the maximum likelihood and Bayesian inference methods. The mitochondrial genome of L. ikeae (GenBank number: OP764680) has a total length of 16,498 bp and encodes 13 PCGs, 22 transfer RNA genes, two ribosomal RNA genes, and a D-loop (control) region. Gene rearrangement is not observed. The mitochondrial genome of L. ikeae exhibits an AT preference, with AT skew > 0 and GC skew < 0 across the entire genome. The phylogenetic relationships of Sicydiinae based on 13 mitochondrial PCG sequences are Sicydium + (Stiphodon + (Sicyopus + Lentipes)) + Sicyopterus, indicating that Sicydium, Sicyopterus, Lentipes, and Stiphodon are all monophyletic groups.

[Nonlinear Variations in PM2. 5 Concentration in the Three Major Urban Agglomerations in China].

ITA and Beast methods were used to quantitatively analyze the nonlinear process of a PM2.5 concentration time series based on the PM2.5 concentration data of the three major urban agglomerations in China. The results showed that： ① the degree of the PM2.5 pollution in the three major urban agglomerations had decreased， and the high-concentration areas had noticeably shrunk. The degree of spatial polarization of PM2.5 concentration was reduced， and the spatial difference was narrowed. The PM2.5 concentration in most areas showed downward trends， but the degree of change was not the same. Compared with the YRD and PRD， the concentration of PM2.5 in the BTH was still at a relatively high level. ② The concentration of PM2.5 in the three major urban agglomerations had seasonal variation characteristics that were high in winter and spring and low in summer and autumn. There were obvious differences in PM2.5 concentration between winter and summer， and the convergence of PM2.5 concentration in summer was greater than that in winter. Areas with high PM2.5 concentration also had obvious downward trends， but the downward trends of PM2.5 concentration in the PRD were not obvious compared with those in the YRD and BTH. ③ The PM2.5 concentration time series of the three major urban agglomerations all had significant downward trends： Beijing-Tianjin-Hebei （BTH） > the Yangtze River Delta （YRD） > the Pearl River Delta （PRD）. The PM2.5 concentration had the largest downward trends in winter. The higher the PM2.5 pollution level， the greater the downward trends. ④ The trend component of the PM2.5 concentration time series in the BTH had two change points， and there was one change point in the seasonal component. The trend and seasonal components of the PM2.5 concentration time series in the YRD had no change point. There was no change point in the seasonal component but one change point in the trend component of the PM2.5 concentration time series in the PRD. These results can provide scientific references for regional air pollution control.

Nomogram for predicting moderate-to-severe sleep-disordered breathing in patients with acute ischaemic stroke: a retrospective cohort study.

OBJECTIVES: Moderate-to-severe sleep-disordered breathing (SDB) is prevalent in patients with acute ischaemic stroke (AIS) and is associated with an increased risk of unfavourable prognosis. We aimed to develop and validate a reliable scoring system for the early screening of moderate-to-severe SDB in patients with AIS, with the objective of improving the management of those patients at risk. STUDY DESIGN: We developed and validated a nomogram model based on univariate and multivariate logistic analyses to identify moderate-to-severe SDB in AIS patients. Moderate-to-severe SDB was defined as an apnoea-hypopnoea index (AHI) ≥15. To evaluate the effectiveness of our nomogram, we conducted a comparison with the STOP-Bang questionnaire by analysing the area under the receiver operating characteristic curve. SETTING: Large stroke centre in northern Shanghai serving over 4000 inpatients, 100 000 outpatients and emergency visits annually. PARTICIPANTS: We consecutively enrolled 116 patients with AIS from the Shanghai Tenth People's Hospital. RESULTS: Five variables were independently associated with moderate-to-severe SDB in AIS patients: National Institutes of Health Stroke Scale score (OR=1.20; 95% CI 0.98 to 1.47), neck circumference (OR=1.50; 95% CI 1.16 to 1.95), presence of wake-up stroke (OR=21.91; 95% CI 3.08 to 156.05), neuron-specific enolase level (OR=1.27; 95% CI 1.05 to 1.53) and presence of brainstem infarction (OR=4.21; 95% CI 1.23 to 14.40). We developed a nomogram model comprising these five variables. The C-index was 0.872, indicated an optimal agreement between the observed and predicted SDB patients. CONCLUSIONS: Our nomogram offers a practical approach for early detection of moderate-to-severe SDB in AIS patients. This tool enables individualised assessment and management, potentially leading to favourable outcomes.

Environmental and dietary exposure to 24 polycyclic aromatic hydrocarbons in a typical Chinese coking plant.

Polycyclic aromatic hydrocarbons (PAHs), known for their health risks, are prevalent in the environment, with the coking industry being a major source of their emissions. To bridge the knowledge gap concerning the relationship between environmental and dietary PAH exposure, we explore this complex interplay by investigating the dietary exposure characteristics of 24 PAHs within a typical Chinese coking plant and their association with environmental pollution. Our research revealed Nap and Fle as primary dietary contaminants, emphasizing the significant influence of soil and atmospheric pollution on PAH exposure. We subjected our data to non-metric multidimensional scaling (NMDS), Spearman correlation analysis, Lasso regression, and Weighted Quantile Sum (WQS) regression to delve into this multifaceted phenomenon. NMDS reveals that dietary PAH exposure, especially within the high molecular weight (HMW) group, is common both within and around the coking plant. This suggests that meals prepared within the plant may be contaminated, posing health risks to coking plant workers. Furthermore, our assessment of dietary exposure risk highlights Nap and Fle as the primary dietary contaminants, with BaP and DahA raising concerns due to their higher carcinogenic potential. Our findings indicate that dietary exposure often exceeds acceptable limits, particularly for coking plant workers. Correlation analyses uncover the dominant roles of soil and atmospheric pollution in shaping dietary PAH exposure. Soil contamination significantly impacts specific PAHs, while atmospheric pollution contributes to others. Additionally, WQS regression emphasizes the substantial influence of soil and drinking water on dietary PAHs. In summary, our study sheds light on the dietary exposure characteristics of PAHs in a typical Chinese coking plant and their intricate interplay with environmental factors. These findings underscore the need for comprehensive strategies to mitigate PAH exposure so as to safeguard both human health and the environment in affected regions.

High titer production of gastrodin enabled by systematic refactoring of yeast genome and an antisense-transcriptional regulation toolkit.

Gastrodin, a phenolic glycoside, is a prominent component of Gastrodia elata, which is renowned for its sedative, hypnotic, anticonvulsant, and neuroprotective activities. Engineering heterologous production of plant natural products in microbial host represents a safe, cost-effective, and scalable alternative to plant extraction. Here, we present the construction of an engineered Yarrowia lipolytica yeast that achieves a high-titer production of gastrodin. We systematically refactored the yeast genome by enhancing the flux of the shikimate pathway and optimizing the glucosyl transfer system. We introduced more than five dozen of genetic modifications onto the yeast genome, including enzyme screening, alleviation of rate-limiting steps, promoter selection, genomic integration site optimization, downregulation of competing pathways, and elimination of gastrodin degradation. Meanwhile, we developed a Copper-induced Antisense-Transcriptional Regulation (CATR) tool. The developed CATR toolkit achieved dynamic repression and activation of violacein synthesis through the addition of copper in Y. lipolytica. This strategy was further used to dynamically regulate the pyruvate kinase node to effectively redirect glycolytic flux towards the shikimate pathway while maintaining cell growth at proper rate. Taken together, these efforts resulted in 9477.1 mg/L of gastrodin in shaking flaks and 13.4 g/L of gastrodin with a yield of 0.149 g/g glucose in a 5-L bioreactor, highlighting the potential for large-scale and sustainable production of gastrodin from microbial fermentation.

Enhanced fatty acid storage combined with the multi-factor optimization of fermentation for high-level production of docosahexaenoic acid in Schizochytrium sp.

Schizochytrium sp. hasreceived much attention for itsability to synthesize and accumulate high-level docosahexaenoic acid (DHA), which can reach nearly 40 % of total fatty acids. In this study, the titer of DHA in Schizochytrium sp. was successfully improved by enhancing DHA storage through overexpressing the diacylglycerol acyltransferase (ScDGAT2C) gene, as well as optimizing the supply of precursors and cofactors required for DHA synthesis by response surface methodology. Notably, malic acid, citric acid, and biotin showed synergistic and time-dependent effects on DHA accumulation. The maximum lipid and DHA titers of the engineered Schizochytrium sp. strain reached 84.28 ± 1.02 g/L and 42.23 ± 0.69 g/L, respectively, with the optimal concentration combination (1.62 g/L malic acid + 0.37 g/L citric acid + 8.28 mg/L biotin) were added 48 h after inoculation. This study provides an effective strategy for improving lipid and DHA production in Schizochytrium sp.