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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.

Abstract Cross-domain recommendation aims to integrate data from multiple domains and introduce information from source domains, thereby achieving good recommendations on the target domain. Recently, contrastive learning has been introduced into the cross-domain recommendations and has obtained some better results. However, most cross-domain recommendation algorithms based on contrastive learning suffer from the bias problem. In addition, the correlation between the user’s single-domain and cross-domain preferences is not considered. To address these problems, a new recommendation model is proposed for cross-domain scenarios based on intra-domain and inter-domain contrastive learning, which aims to obtain unbiased user preferences in cross-domain scenarios and improve the recommendation performance of both domains. Firstly, a network enhancement module is proposed to capture users’ complete preference by applying a graphical convolution and attentional aggregator. This module can reduce the limitations of only considering user preferences in a single domain. Then, a cross-domain infomax objective with noise contrast is presented to ensure that users’ single-domain and cross-domain preferences are correlated closely in sequential interactions. Finally, a joint training strategy is designed to improve the recommendation performances of two domains, which can achieve unbiased cross-domain recommendation results. At last, extensive experiments are conducted on two real-world cross-domain scenarios. The experimental results show that the proposed model in this paper achieves the best recommendation results in comparison with existing models.

Abstract Whether small nucleolar RNAs (snoRNAs) are involved in the regulation of liver cancer stem cells (CSCs) self-renewal and serve as therapeutic targets remains largely unclear. Here we show that a functional snoRNA (SNORD88B) is robustly expressed in Hepatocellular carcinoma (HCC) tumors and liver CSCs. SNORD88B deficiency abolishes the self-renewal of liver CSCs and hepatocarcinogenesis. Mechanistically, SNORD88B anchors WRN in the nucleolus, promoting XRCC5 interacts with STK4 promoter to suppress its transcription, leading to inactivation of Hippo signaling. Moreover, low expression of STK4 and high expression of XRCC5 are positively correlated with HCC poor prognosis. Additionally, snord88b knockout suppresses mouse liver tumorigenesis. Notably, co-administration of SNORD88B antisense oligonucleotides (ASOs) with MST1 agonist adapalene (ADA) exert synergistic antitumor effects and increase overall murine survival. Our findings delineate that SNORD88B drives self-renewal of liver CSCs and accelerates HCC tumorigenesis via non-canonical mechanism, providing potential targets for liver cancer therapy by eliminating liver CSCs.

BackgroundThe association between obstructive sleep apnea (OSA) and plasma lipid concentrations is not consistent. This study aimed to investigate the association of plasma lipid concentrations with the prevalence of OSA among US adults, with an additional examination of the mediating effect of body mass index (BMI).MethodsThis cross-sectional study included 8,086 individuals who participated in the National Health and Nutrition Examination Survey (NHANES), conducted from 2005 to 2008 and 2015–2018. Multivariable logistic regression analysis was conducted to compute the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between plasma lipid concentrations and the prevalence of OSA. Additionally, subgroup analysis was used to explore the potential interactions. Generalized additive models (GAM) were constructed to evaluate the nonlinear relationships between lipid concentrations and OSA. Furthermore, mediation analysis was performed to assess the potential mediating role of BMI.ResultsIn the fully adjusted model, when comparing the lowest quartile, the ORs for the prevalence of OSA among participants in the highest quartile were 1.367 (95% CI, 1.107–1.688) for triglyceride and 1.212 (95% CI, 1.004–1.462) for low-density lipoprotein cholesterol (LDL-C). However, total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) were not associated with OSA. Notably, the relationship between triglyceride and OSA differed in the subgroups of gender, race, and body mass index (BMI) (P for interaction

Star3 is located in sex hormone synthesis signaling pathway associated with gonadal development. In this study, star3 was first cloned from the gonad of Hyriopsis cumingii. The cDNA of star3 in H. cumingii was 2072 bp in length, concluding an open reading frame (ORF) of 1419 bp, encoding 472 amino acids with a conserved START structural domain. Tissue distribution analysis showed star3 highest expressed mainly in gonad, which had higher transcription levels in testis than that in ovary. Significant hybridization signals were detected on the follicle wall cell of male gonad. Gonad expression patterns revealed star3 highest expressed at two months old during juvenile stages. After RNA interference with star3, expression levels of cyp17a and 17β-hsd11 was repressed. Furthermore, contents of pregnenolone, testosterone, and estradiol in gonad were reduced significantly. These results suggest star3 may be involved in sex hormone synthesis and play an important role in early gonadal development of H. cumingii.

Abstract 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.

Abstract Sodium‐ion batteries (NIBs) have become an ideal alternative to lithium‐ion batteries in the field of electrochemical energy storage due to their abundant raw materials and cost‐effectiveness. With the progress of human society, the requirements for energy storage systems in extreme environments, such as deep‐sea exploration, aerospace missions, and tunnel operations, have become more stringent. The comprehensive performance of NIBs at low temperatures (LTs) has also become an important consideration. Under LT conditions, challenges such as increased viscosity of electrolyte, abnormal growth of solid electrolyte interface, and poor contact between collector and electrode materials emerge. The aforementioned issues hinder the diffusion kinetics of sodium ions (Na+) at the electrode/electrolyte interface and cause rapid degradation of battery performance. Consequently, the optimization of electrolyte composition and cathode/anode materials becomes an effective approach to improve LT performance. This review discusses the conduction behavior and limiting factors of Na+ in both solid electrodes and liquid electrolytes at LT. Furthermore, it systematically reviews the recent research progress of LT NIBs from three aspects: cathode materials, anode materials, and electrolyte components. This review aims to provide a valuable reference for developing high‐performance LT NIBs.

BackgroundDigital technologies have penetrated most workplaces. However, it is unclear how such digital technologies affect the physical health of older workers. ObjectiveThis scoping review aims to examine and summarize the evidence from scientific literature concerning the impact of digital technology on the physical health of older workers. MethodsThis scoping review will be conducted following recommendations outlined by Levac et al and will adhere to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews) guidelines for reporting. Peer-reviewed papers written in English will be searched in the following databases: MEDLINE, Cochrane, ProQuest, Web of Science, Scopus, APA PsycInfo, and ERIH PLUS. The web-based systematic review platform Covidence will be used to create a data extraction template. It will cover the following items: study and participant characteristics, health measures, digital tool characteristics and usage, and research findings. Following the Population, Concept, and Context (PCC) framework, our review will focus on studies involving older workers aged 50 years or older, any form of digital technology (including teleworking and the use of digital tools at work), and how digital technologies affect physical health (such as vision loss, musculoskeletal disorders, and migraines). Studies that focus only on mental health will be excluded. Study selection based on title and abstract screening (first stage), full-text review (second stage), and data extraction (third stage) will be performed by a group of researchers, whereby each paper will be reviewed by at least 2 people. Any conflict regarding the inclusion or exclusion of a study and the data extraction will be resolved by discussion between the researchers who evaluated the papers; a third researcher will be involved if consensus is not reached. ResultsA preliminary search of MEDLINE, Epistemonikos, Cochrane, PROSPERO, and JBI Evidence Synthesis was conducted, and no current or ongoing systematic reviews or scoping reviews on the topic were identified. The results of the study are expected in April 2025. ConclusionsOur scoping review will seek to provide an overview of the available evidence and identify research gaps regarding the effect of digital technology and the use of digital tools in the work environment on the physical health of older workers. International Registered Report Identifier (IRRID)PRR1-10.2196/59900

ObjectivesTo investigate the safety and cost analysis of oral propranolol treatment for high-risk infantile hemangiomas starting from the outpatient setting.MethodsA total of 41 high-risk infantile hemangioma patients from outpatient settings and 43 from inpatient settings were selected for the study. After routine pre-treatment examinations, patients were administered propranolol in a stepwise incremental dosing regimen over three consecutive days in the outpatient clinic. Changes in heart rate, blood pressure and PR interval before and after medication were compared. On the 10th day post-medication, liver and kidney functions, fasting blood glucose, tumor ultrasonography, and electrocardiogram were re-evaluated. The costs of treatment starting from the outpatient clinic (including pre-treatment examinations and the first three days of treatment) were calculated and compared with those of similarly managed inpatient cases.ResultsThe majority of patients exhibited a reduction in heart rate and blood pressure, as well as an extended PR interval after treatment of medication (P < 0.05), which remained within normal limits without clinical symptoms. On the 10th day post-medication, statistical differences in blood biochemistry and electrocardiograms were observed when compared to pre-treatment values (P < 0.05), but all values remained within normal ranges. No severe adverse reactions such as hypoglycemia occurred. Additionally, the cost of treatment from the outpatient clinic was significantly lower than that of inpatient care.ConclusionOral propranolol treatment for high-risk infantile hemangiomas starting from the outpatient setting is associated with few adverse reactions and significantly reduced treatment costs. It is worthy of broader application in hospitals without dermatology wards.

Abstract Chinese classical gardens are a significant cultural heritage in the history of world gardening, with their central architectural principle of "scenes changing as steps move" (步移景异) embodying traditional Chinese aesthetic ideals. This study employed the variation of visual complexity during a tour as a representation of this principle, using Jingxinzhai (静心斋) Garden as a case study. The visual environmental characteristics were quantified using the Fraclab box-counting, Canny edge detection, and DeepLab V3 + model, and the spatial distribution of fractal dimension and visual index of landscape elements were analyzed. Through partial correlation analysis, hierarchical regression analysis, and one-way ANOVA, the relevant factors (BVI, RVI, GVI, WVI) and influencing factors (BVI, RVI, GVI) and the differences among landscape element combinations of visual complexity were identified. Furthermore, the distribution patterns and causes of visual complexity in Chinese classical gardens were then discussed. This study proposes an effective method for quantifying the visual environmental characteristics of Chinese classical gardens and provides an explanation of the concept of "scenes changing as steps move" from the perspective of visual environment. It offers important references for a deeper understanding of Chinese classical garden design and planning.

Gut microbes are closely related with human health, but remain much to learn. Clostridium symbiosum is a conditionally pathogenic human gut bacterium and regarded as a potential biomarker for early diagnosis of intestinal tumors. However, the absence of an efficient toolbox that allows diverse genetic manipulations of this bacterium limits its in-depth studies. Here, we obtained the complete genome sequence of C. symbiosum ATCC 14940, a representative strain of C. symbiosum. On this basis, we further developed a series of genetic manipulation methods for this bacterium. Firstly, following the identification of a functional replicon pBP1 in C. symbiosum ATCC 14940, a highly efficient conjugative DNA transfer method was established, enabling the rapid introduction of exogenous plasmids into cells. Next, we constructed a dual-plasmid CRISPR/Cas12a system for genome editing in this bacterium, reaching over 60 % repression for most of the chosen genes as well as efficient deletion (>90 %) of three target genes. Finally, this toolbox was used for the identification of crucial functional genes, involving growth, synthesis of important metabolites, and virulence of C. symbiosum ATCC 14940. Our work has effectively established and optimized genome editing methods in intestinal C. symbiosum, thereby providing strong support for further basic and application research in this bacterium.

Due to the complex growth positions of dragon fruit and the difficulty in robotic picking, this paper proposes a six degrees of freedom dragon fruit picking robot and investigates the manipulator’s motion characteristics to address the adaptive motion issues of the picking manipulator. Based on the agronomic characteristics of dragon fruit cultivation, the structural design of the robot and the dimensions of its manipulator were determined. A kinematic model of the dragon fruit picking robot based on screw theory was established, and the workspace of the manipulator was analyzed using the Monte Carlo method. Furthermore, a dynamic model of the manipulator based on the Kane equation was constructed. Performance experiments under trajectory and non-trajectory planning showed that trajectory planning significantly reduced power consumption and peak torque. Specifically, Joint 3’s power consumption decreased by 62.28%, and during the picking, placing, and resetting stages, the peak torque of Joint 4 under trajectory planning was 10.14 N·m, 12.57 N·m, and 16.85 N·m, respectively, compared to 12.31 N·m, 15.69 N·m, and 22.13 N·m under non-trajectory planning. This indicated that the manipulator operates with less impact and smoother motion under trajectory planning. Comparing the dynamic model simulation and actual testing, the maximum absolute error in the joint torques was −2.76 N·m, verifying the correctness of the dynamic equations. Through field picking experiments, it was verified that the machine’s picking success rate was 66.25%, with an average picking time of 42.4 s per dragon fruit. The manipulator operated smoothly during each picking process. In the study, the dragon fruit picking manipulator exhibited good stability, providing the theoretical foundation and technical support for intelligent dragon fruit picking.

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.

Summary: This comprehensive review delves into the significance of androgens in cervical cancer, examining both epidemiological evidence and the underlying biological mechanisms. Cervical cancer ranks as the fourth most prevalent cancer among women globally, with disproportionately higher incidence and mortality rates in less developed regions where cervical human papillomavirus (HPV) screening remains limited. Recent research highlights the previously underexplored role of androgens in cervical cancer. Notably, cervical tissues house androgen receptors, and elevated levels of endogenous androgens have been linked to an increased risk of cervical cancer. Androgens exert their influence on the development and progression of cervical cancer by impacting key cellular processes, including proliferation, apoptosis, differentiation, and epithelial cell transformation. Furthermore, specific HPV subtypes may interact with androgens, potentially modulating HPV-related cellular degeneration and transformation. In light of these findings, it is evident that androgens assume a crucial role in cervical cancer’s pathogenesis. Consequently, further investigations are warranted to deepen our understanding of the intricate relationship between androgens and cervical cancer. Such knowledge advancements can facilitate improved strategies for early prevention and treatment of cervical cancer, especially in regions with limited HPV screening access. This review underscores the importance of considering androgens as a vital component of the multifaceted landscape of cervical cancer etiology and progression, ultimately contributing to more effective clinical interventions.

Abstract Background Berberine (BBR) is a commonly used anti-intestinal inflammation drug, and its anti-cancer activity has been found recently. BBR can intervene and control malignant colorectal cancer (CRC) through intestinal microbes, but the direct molecular target and related mechanism are unclear. This study aimed to identify the target of BBR and dissect related mechanisms against the occurrence and development of CRC from the perspective of intestinal microorganisms. Results Here, we found that BBR inhibits the growth of several CRC-driving bacteria, especially Peptostreptococcus anaerobius. By using a biotin-conjugated BBR derivative, we identified the protein FtfL (formate tetrahydrofolate ligase), a key enzyme in C1 metabolism, is the molecular target of BBR in P. anaerobius. BBR exhibits strong binding affinity and potent inhibition on FtfL. Based on this, we determined the crystal structure of PaFtfL (P. anaerobius FtfL)-BBR complex and found that BBR can not only interfere with the conformational flexibility of PaFtfL tetramer by wedging the tetramer interface but also compete with its substrate ATP for binding within the active center. In addition, the enzymatic activities of FtfL homologous proteins in human tumor cells can also be inhibited by BBR. Conclusions In summary, our study has identified FtfL as a direct target of BBR and uncovered molecular mechanisms involved in the anti-CRC of BBR. BBR interferes with intestinal pathogenic bacteria by targeting FtfLs, suggesting a new means for controlling the occurrence and development of CRC.

Abstract Formic acid (FA) has emerged as a promising one-carbon feedstock for biorefinery. However, developing efficient microbial hosts for economically competitive FA utilization remains a grand challenge. Here, we discover that the bacterium Vibrio natriegens has exceptional FA tolerance and metabolic capacity natively. This bacterium is remodeled by rewiring the serine cycle and the TCA cycle, resulting in a non-native closed loop (S-TCA) which as a powerful metabolic sink, in combination with laboratory evolution, enables rapid emergence of synthetic strains with significantly improved FA-utilizing ability. Further introduction of a foreign indigoidine-forming pathway into the synthetic V. natriegens strain leads to the production of 29.0 g · L−1 indigoidine and consumption of 165.3 g · L−1 formate within 72 h, achieving a formate consumption rate of 2.3 g · L−1 · h−1. This work provides an important microbial chassis as well as design rules to develop industrially viable microorganisms for FA biorefinery.

Abstract The oleaginous yeast, Yarrowia lipolytica, has garnered much attention and is gaining recognition as a potential industrial platform for nutraceutical production. The superior properties of Y. lipolytica include its transparent inherited background, broad substrate spectrum, and superior environmental tolerance. Specifically, advances in genetic tools and engineering strategies have further widened its applications in metabolic engineering and biomanufacturing. In this review, we summarized developments in synthetic biology and engineering strategies for constructing Y. lipolytica to produce nutraceuticals. We also proposed perspectives on the limitations and challenges in developing microbial Y. lipolytica factories.

Abstract In the context of the rapid development of low-carbon economy, there has been increasing interest in utilizing naturally abundant and cost-effective one-carbon (C1) substrates for sustainable production of chemicals and fuels. Moorella thermoacetica, a model acetogenic bacterium, has attracted significant attention due to its ability to utilize carbon dioxide (CO2) and carbon monoxide (CO) via the Wood–Ljungdahl (WL) pathway, thereby showing great potential for the utilization of C1 gases. However, natural strains of M. thermoacetica are not yet fully suitable for industrial applications due to their limitations in carbon assimilation and conversion efficiency as well as limited product range. Over the past decade, progresses have been made in the development of genetic tools for M. thermoacetica, accelerating the understanding and modification of this acetogen. Here, we summarize the physiological and metabolic characteristics of M. thermoacetica and review the recent advances in engineering this bacterium. Finally, we propose the future directions for exploring the real potential of M. thermoacetica in industrial applications.

Background and objectiveAberrant 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.MethodsTrophoblasts 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.ResultsWe found that expression of mono-, di-, and tri-methylation of histone H3 lysine 9 (H3K9me1, H3K9me2 and H3K9me3) was significantly increased, p

ObjectivesTo look into the connection between amyotrophic lateral sclerosis (ALS) and atrial fibrillation (AF) using Mendelian randomization (MR).MethodsTwo-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.ResultsThe 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.ConclusionsThis MR study proves a positive causal connection between ALS and atrial fibrillation. Further studies are warranted to elucidate the mechanisms linking ALS and AF.

The paper reports a series of experimental and numerical data of destructive stub column tests on additively manufactured steel parts stiffened by surface sinusoidal wave patterns. The specimens were made in 316L stainless steel and manufactured by selective laser melting (SLM). The experimental tests covered five tensile coupon tests, fourteen square hollow section (SHS) stub column tests and measurements of geometric imperfections of the stub columns. Numerical models incorporating the measured material and geometric properties were developed and analysed via GMNIA approach. The validity of the numerical models is demonstrated by their accurate replications of the load-end shortening responses of the tested specimens. The reported dataset will contribute to the stability design and characterisation of thin-walled steel plated structures with advanced stiffening patterns.

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.

Microbial utilization and conversion of organic one-carbon compounds, such as formate and methanol that can be easily produced from CO2, has emerged as an attractive approach for biorefinery. In this study, we discovered Clostridium beijerinckii NCIMB 8052, a typical solventogenic Clostridium strain, to be a native formate-utilizing bacterium. 13C isotope analysis showed that formate could be metabolized via both assimilation and dissimilation pathways in C. beijerinckii NCIMB 8052. Notably, the use of formate as the supplementary substrate by this strain could significantly enhance its glucose consumption and ABE (acetone-butanol-ethanol) production, largely due to the up-regulation of genes responsible for glycolysis and glucose transport under formate stress. Based on these findings, we further improved formate tolerance of C. beijerinckii NCIMB 8052 by adaptive laboratory evolution, generating an evolved strain Cbei-FA01. The Cbei-FA01 strain could produce 23.0 g/L of ABE solvents using glucose and formate as dual substrates, ∼50% higher than that of the wild-type strain under the same condition. Moreover, such a promotion effect of formate on ABE production by Cbei-FA01 was also observed in fermenting a glucose-xylose mixture. This work reveals a previously unreported role of formate in biological ABE production, providing a new approach to utilize this one-carbon source.

Hg(II), as an extremely hazardous heavy metal contaminant in the environment, poses a significant potential hazard to human health and ecosystems. A GR-MWCNTs-COOH/CeO2/Nafion composite film-modified glassy carbon electrode was prepared using the drop-casting method in this study. The GR-MWCNTs-COOH/CeO2/Nafion/GCE was electrochemically investigated through cyclic voltammetry (CV) and differential pulse stripping voltammetry (DPSV). Additionally, the surface morphologies of the composite film were evaluated using scanning electron microscopy (SEM). The conditions, such as buffer solution, pH, deposition potential, deposition time, modified film thickness, and Nafion content, were optimized. Under optimal experimental conditions, a good linear relationship between the peak current response of Hg(II) and its concentration in the range of 5–100 μg·L−1 was observed, with a detection limit of 0.389 μg·L−1. When it was used to detect Hg(II) in offshore seawater, the recovery rate ranged from 94.72% to 103.8%, with RSDs ≤ 5.79%.

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.

ObjectiveThe government has recently implemented reforms aimed at delegating power, streamlining administration, and optimizing government services. This reform has eliminated barriers that impede the growth of various industries, thereby unleashing innovative potential. Additionally, there have been several medical policies, including changes to medical insurance and centralized volume-based procurement. China’s pharmaceutical market has undergone significant changes, leading to increased demands for innovation technology efficiency in pharmaceutical manufacturing.MethodsThe three-stage BCC theory was employed to assess the effectiveness of technology innovation in the industry under this reform. Calculate precise comprehensive technical efficiency values, pure technical efficiency values, and scale efficiency values for technological innovation in the pharmaceutical industry across 30 provinces from 2018 to 2020, after removing environmental factors.ResultsIn 2020, Jiangsu and Shandong and nine other provinces reached the comprehensive technical efficiency frontier surface, joining Tianjin, Zhejiang, and Guangdong provinces. However, Gansu, Qinghai, Ningxia, and Xinjiang still need to catch up due to their smaller industrial scale and lack of technology.DiscussionTo ensure the effectiveness of reforms, it is crucial to fully consider provincial differences. Articulating national and provincial policies is necessary to allow efficient provinces to continue and allocate resources toward less efficient provinces to improve overall efficiency.

Background The predictive factors of blood pressure (BP) response to continuous positive airway pressure (CPAP) in obstructive sleep apnoea (OSA) are still being explored. We aimed to assess the antihypertensive effect of CPAP considering the obstructive respiratory event-triggered BP surge profiles in 130 subjects with severe OSA and untreated hypertension.Methods Nocturnal BP was monitored continuously and synchronised with polysomnography. Event-triggered BP surge profiles were studied: BP surge as the value of event-related systolic BP (SBP) elevation; BP index as the number of BP surge events of ≥10 mm Hg per hour. Patients were then divided into two groups according to the median BP index (high and low BP surge groups) and assigned to 4 weeks of CPAP. Changes in BPs and plasma biomarkers were compared. After the initial evaluation, patients with a better BP response in the high BP surge group were then followed up for the second evaluation at 24 months.Results Overall, a modest decrease was observed in both office and asleep BPs at the 4-week follow-up; however, BPs dropped more markedly in patients in the high BP surge group than those in the low BP surge group, in both office SBP (5.3 mm Hg vs 2.2 mm Hg, p=0.003) and diastolic BP (4.0 mm Hg vs 1.2 mm Hg, p

A yeast host Yarrowia lipolytica is genetically engineered to overcome rate-limiting steps and synthesize the cannabinoid precursor olivetolic acid.

Objective: Elucidating the concurrence and interdependence of three precipitating factors as contributors of a subset of secondary burning mouth syndrome (BMS), which is defined having detectable precipitating factors. Design: 47 secondary BMS and 15 non-BMS cases were sourced from medical records of an Oral Pathology Specialty Clinic in Canada (2017–2021). Each case had Cytology, Hematology, and Sialometry tests to detail the state of three precipitating factors (the presence of fungal hyphae, hypovitaminosis D, and objective oral dryness). Three factors were compared between secondary BMS and non-BMS groups independently, in pairs, and as a triple-factor by Fisher's exact tests, Contingency Coefficients, and Logistic Regressions. Results: Rates of objective oral dryness (89.36%) and hypovitaminosis D (74.47%) in the secondary BMS group significantly differ from the non-BMS group (p = 0.0013, p = 0.0016). No difference was found in the incidence of fungal hyphae between BMS (91.49%) and non-BMS groups (p = 0.0881). Rates of three precipitating factors in pairs and as a triple-factor within the secondary BMS group significantly differ from the non-BMS group (p-values from 0.0011 to

Abstract Escherichia coli, one of the most efficient expression hosts for recombinant proteins (RPs), is widely used in chemical, medical, food and other industries. However, conventional expression strains are unable to effectively express proteins with complex structures or toxicity. The key to solving this problem is to alleviate the host burden associated with protein overproduction and to enhance the ability to accurately fold and modify RPs at high expression levels. Here, we summarize the recently developed optimization strategies for the high-level production of RPs from the two aspects of host burden and protein activity. The aim is to maximize the ability of researchers to quickly select an appropriate optimization strategy for improving the production of RPs.

Innate lymphoid cells (ILC) have been shown to be involved in a range of inflammatory contexts but how their cellular lineage is regulated is not fully established. Here the authors show a role for circular RNA circTmem241 in the differentiation of ILC3 via initiation of Elk3 transcription.

Introduction: The normalized implementation of the centralized volume-based procurement policy for pharmaceuticals is a concerted push for supply-side structural reform of the pharmaceutical industry in China. The impact of the centralized drug procurement policy on pharmaceutical companies' transition from imitation to innovation is investigated to test whether a positive effect occurs in the innovation landscape of the pharmaceutical market. Methods: The double difference method and a series of robustness tests were used based on data from a sample of listed pharmaceutical companies in Shanghai and Shenzhen A-shares between 2015 and 2021. Results: The study found that the centralized drug procurement policy significantly contributed to the increased intensity of innovation input in the Chinese pharmaceutical industry. In terms of regional and firm nature heterogeneity, it was found that firms in the seven provinces belonging to the three economic regions had a better increase in innovation input intensity than other regions. Firms of state-owned nature had a better increase in innovation input intensity than private companies. The mechanism test found a partial mediating effect of nearly 10% for the cost of sales rate on the innovation input intensity of listed companies and a negative mediating effect on corporate operating profit. Discussion: Further research found that the effect of centralized drug procurement policy on the improvement of innovation quality of listed pharmaceutical companies was evident. The innovation development of Chinese pharmaceutical companies no longer focused on the accumulation of innovation quantity.

Abstract Background Studies on deep learning (DL)-based models in breast ultrasound (US) remain at the early stage due to a lack of large datasets for training and independent test sets for verification. We aimed to develop a DL model for differentiating benign from malignant breast lesions on US using a large multicenter dataset and explore the model’s ability to assist the radiologists. Methods A total of 14,043 US images from 5012 women were prospectively collected from 32 hospitals. To develop the DL model, the patients from 30 hospitals were randomly divided into a training cohort (n = 4149) and an internal test cohort (n = 466). The remaining 2 hospitals (n = 397) were used as the external test cohorts (ETC). We compared the model with the prospective Breast Imaging Reporting and Data System assessment and five radiologists. We also explored the model’s ability to assist the radiologists using two different methods. Results The model demonstrated excellent diagnostic performance with the ETC, with a high area under the receiver operating characteristic curve (AUC, 0.913), sensitivity (88.84%), specificity (83.77%), and accuracy (86.40%). In the comparison set, the AUC was similar to that of the expert (p = 0.5629) and one experienced radiologist (p = 0.2112) and significantly higher than that of three inexperienced radiologists (p

Abstract Non/semi‐rational engineering strategies can improve the performance of microbial cell factories under the situations of indistinct metabolic regulations and interactions. However, generating positive variants through these strategies is remarkably low. Using traditional screening methods to evaluate the performance of mutants, such as mass spectrometry and chromatography, is low‐throughput, slow‐detection, and labor‐intensive. Specifically, the efficiency of high‐throughput screening (HTS) for strain screening could reach even more 103−106 strains/day, bridging the gap between non/semi‐rational engineering strategies and microbial cell factories construction. This review highlights transcription factor (TFs)‐based biosensors in the advances in developing synthetic biosensors for HTS. We hope that this review will help take full advantage of valuable TFs to guide the HTS technology and promote its development.

The fact of the matter is that Chinese modernization is not only a great creation of CPC, but also a path we must take to realize the rejuvenation of the Chinese nation. Therefore, This paper holds that we should focus on the theme of the national rejuvenation and deeply understand the historical exploration of Chinese modernization. And it is necessary to base ourselves on China’s national conditions and fully understand the scientific connotation of Chinese modernization. Besides, we should integrate with the times and firmly grasp the practical requirements of Chinese modernization.Only in this way can we firmly follow the path of Chinese modernization and promote the great rejuvenation of the Chinese nation.

This study aims to establish precise quality indicators for evaluating and enhancing ultrasound performance, employing a methodology based on a comprehensive review of the literature, expert insights, and practical application experiences. We conducted a thorough review of both the domestic and international literature on ultrasound quality control to identify potential indicators. A dedicated team was formed to oversee the complete indicator development process. Utilizing a three-round modified Delphi method, we sought expert opinions through personalized email correspondence. Subsequently, data from diverse hospital indicators were collected to validate and assess feasibility. A novel set of seven indicators was compiled initially, followed by the convening of a 36-member nationally representative expert panel. After three rounds of meticulous revisions, consensus was reached on 13 indicators across three domains. These finalized indicators underwent application in various hospital settings, demonstrating their initial validity and feasibility. The development of thirteen ultrasound quality indicators represents a significant milestone in evaluating ultrasound performance. These indicators empower hospitals to monitor changes in quality effectively, fostering efficient quality management practices.

With the rapid development of object detection technology for unmanned aerial vehicles (UAVs), it is convenient to collect data from UAV aerial photographs. They have a wide range of applications in several fields, such as monitoring, geological exploration, precision agriculture, and disaster early warning. In recent years, many methods based on artificial intelligence have been proposed for UAV object detection, and deep learning is a key area in this field. Significant progress has been achieved in the area of deep-learning-based UAV object detection. Thus, this paper presents a review of recent research on deep-learning-based UAV object detection. This survey provides an overview of the development of UAVs and summarizes the deep-learning-based methods in object detection for UAVs. In addition, the key issues in UAV object detection are analyzed, such as small object detection, object detection under complex backgrounds, object rotation, scale change, and category imbalance problems. Then, some representative solutions based on deep learning for these issues are summarized. Finally, future research directions in the field of UAV object detection are discussed.

Background and objectiveProteinuria and glomerular endotheliosis are characteristics of glomerular injury in preeclampsia, a hypertensive disorder in human pregnancy. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are biomarkers of acute/chronic renal tubule injury. To determine if tubule injury occurs in preeclampsia, we determined maternal plasma and urine NGAL and KIM-1 levels and evaluated NGAL and KIM-1 expression in kidney biopsy specimens from women with preeclampsia.MethodsPrenatal and postpartum maternal blood and urinary samples were collected from three groups of pregnant women: normal pregnancy (n = 100), preeclampsia (n = 83), and pregnancy complicated with chronic hypertension (n = 20). Plasma and urine levels of NGAL and KIM-1 were measured by ELISA. Kidney biopsy tissue sections from patients with preeclampsia (n = 5) were obtained from Pathology Archives and processed to determine NGAL and KIM-1 expression by immunostaining and high kidney solution images were assessed by electron microscopy (EM).ResultsPrenatal plasma and urine levels of NGAL and KIM-1 were significantly higher in preeclamptic than in normal controls, p < 0.01. In normal pregnancy, both plasma and urine levels of NGAL and KIM-1 at 24–48 h after delivery and 6–8 weeks postpartum were relatively comparable to that of antenatal levels. In preeclampsia, urine, but not plasma, NGAL levels were reduced at 6–8 weeks postpartum compared to the antenatal levels, p < 0.05. Although maternal and urine KIM-1 levels were reduced at 6–8 weeks postpartum compared to the antenatal levels in preeclampsia, the levels were still higher than those in normal pregnancy. Positive expression of NGAL and KIM-1 was detected in proximal tubule epithelial cells in kidney tissue specimens from preeclampsia but not in non-pregnancy controls. EM examination showed glomerular and tubular injury in preeclampsia.ConclusionOur findings of increased maternal levels and urine secretion of NGAL and KIM-1, along with the upregulation of NGAL and KIM-1 expression in tubular epithelial cells in preeclampsia, provide plausible evidence that tubular injury exists in preeclampsia. The higher postpartum NGAL and KIM-1 levels in preeclamptic pregnancies indicate that tubular injury would not resolve within 2–3 months after delivery and suggest that proper follow-up and management of kidney function in women with preeclampsia would be necessary to reduce chronic kidney diseases in those women later in life.

IntroductionCleidocranial dysplasia (CCD) is an autosomal-dominant, heritable skeletal and dental disease, involving hypoplastic clavicles, defective ossification of the anterior fontanelle, dentin and enamel hypoplasia, and supernumerary teeth, which can seriously affect the oral and mental health of patients. Amyloid-like protein aggregation, which is established by lysozyme conjugated with polyethylene glycol (Lyso-PEG), forms a mineralized nanofilm layer on a healthy enamel surface. However, whether it can form a remineralization layer in dental tissues from CCD remains unclear.MethodsThis study evaluated deciduous teeth from healthy individuals and a patient with CCD. Because pulp and dentin are functionally closely related, stem cells from human exfoliated deciduous teeth (SHED) from CCD patients and healthy individuals were collected to compare their biological properties.ResultsThe results found that deciduous teeth from patients with CCD exhibited dentin hypoplasia. In addition, the proliferative ability and osteogenic potential of SHED from patients with CCD were lower than those of control individuals. Finally, Lyso-PEG was applied to dentin from the CCD and control groups, showing a similar remineralization-induced effect on the dentin surfaces of the two groups.ConclusionThese results extend our understanding of the dentin and SHED of patients with CCD, exhibiting good caries-preventive capacity and good biocompatibility of Lyso-PEG, thus providing a novel dental therapy for CCD and patients with tooth hypoplasia.

Metabolic adaptation has been reported to promote cancer, yet the underlying mechanisms are not clear. Here, the authors show that m1A methylation in tRNA regulates cholesterol metabolism in liver cancer stem cells and m1A inhibition decreases tumourigenesis in preclinical models of hepatocellular carcinoma.

Background and objectiveCOVID-19 infection in pregnancy significantly increases risks of adverse pregnancy outcomes. However, little is known how the innate immunity at the placental maternal-fetal interface responds to COVID-19 infection. Type I IFN cytokines are recognized as a key component of the innate immune response against viral infection. In this study, we specifically evaluated expression of IFN antiviral signaling molecules in placentas from women infected with COVID-19 during pregnancy.MethodsExpression of IFN activation signaling pathway molecules, including cyclic GMP–AMP synthase (cGAS), stimulator of interferon genes (STING), interferon regulatory factor 3 (IRF3), Toll-like receptor 7 (TLR7), mitochondrial antiviral-signaling protein (MAVS), and IFNβ were determined in formalin-fixed paraffin embedded (FFPE) placental tissue sections (villous and fetal membrane) by immunostaining. A total of 20 placentas were examined, 12 from COVID-19 patients and 8 from non-COVID-19 controls. Patient demographics, clinical data, and placental pathology report were acquired via EPIC medical record review.ResultsExcept BMI and placental weight, there was no statistical difference between COVID and non-COVID groups in maternal age, gestational age at delivery, gravity/parity, delivery mode, and newborn gender and weight. In COVID-exposed group, the main pathological characteristics in the placental disc are maternal and fetal vascular malperfusion and chronic inflammation. Compared to non-COVID controls, expression of IFN activation pathway molecules were all upregulated with distinct cell-type specific distribution in COVID-exposed placentas: STING in villous and decidual stromal cells; IRF3 in cytotrophoblasts (CTs) and extra-villous trophoblasts (EVTs); and TLR7 and MAVS in syncytiotrophoblasts (STs), CTs, and EVTs. Upregulation of STING, MAVS and TLR7 was also seen in fetal endothelial cells.ConclusionsSTING, IRF3, TLR7, and MAVS are key viral sensing molecules that regulate type I IFN production. Type I IFNs are potent antiviral cytokines to impair and eradicate viral replication in infected cells. The finding of cell-type specific distribution and activation of these innate antiviral molecules at the placental maternal-fetal interface provide plausible evidence that type I IFN pathway molecules may play critical roles against SARS-CoV-2 infection in the placenta. Our findings also suggest that placental maternal-fetal interface has a well-defined antiviral defense system to protect the developing fetus from SARS-CoV-2 infection.

BackgroundIatrogenic tracheoesophageal fistula (TEF) is a rare but life-threatening condition. No consensus has been reached regarding TEF treatment, though, stenting has been gaining popularity for less invasiveness than thoracic surgery. The airway management during stent placement for TEF could be challenging.Case presentationsWe report a patient who suffered from TEF after cardiac surgery with symptoms of persistent coughing and aspiration. He who was admitted for stent placement but ended up in failure and referred to our institution for further treatment. We successfully took advantage of the supraglottic jet oxygenation and ventilation (SJOV) during stent placement.ConclusionThis is the first case so far describing SJOV in complicated stenting treatment. This demonstrates that SJOV can be applied for stent placement in TEF patients with restricted airways.

Introduction: Systematic gene knockout studies may offer us novel insights on cell metabolism and physiology. Specifically, the lipid accumulation mechanism at the molecular or cellular level is yet to be determined in the oleaginous yeast Y. lipolytica.Methods: Herein, we established ten engineered strains with the knockout of important genes involving in central carbon metabolism, NADPH generation, and fatty acid biosynthetic pathways.Results: Our result showed that NADPH sources for lipogenesis include the OxPP pathway, POM cycle, and a trans-mitochondrial isocitrate-α-oxoglutarate NADPH shuttle in Y. lipolytica. Moreover, we found that knockout of mitochondrial NAD+ isocitrate dehydrogenase IDH2 and overexpression of cytosolic NADP+ isocitrate dehydrogenase IDP2 could facilitate lipid synthesis. Besides, we also demonstrated that acetate is a more favorable carbon source for lipid synthesis when glycolysis step is impaired, indicating the evolutionary robustness of Y. lipolytica.Discussion: This systematic investigation of gene deletions and overexpression across various lipogenic pathways would help us better understand lipogenesis and engineer yeast factories to upgrade the lipid biomanufacturing platform.

Summary: Background: With the growing demand for breast screening in public health services and clinical care, ultrasound departments in China are facing tremendous challenges. Methods: A cross-sectional nationwide survey was conducted in 5,460 departments providing ultrasound diagnoses in mainland China from 2020 to 2021. The survey included general information about the ultrasound department, the characteristics of sonologists, the use of Breast Imaging Reporting and Data System (BI-RADS) templates, and the diagnostic accuracy rate of breast cancer ultrasound. Findings: There were on average 2.25 sonologists per 10,000 patients in mainland China per year. The average utilization rate of BI-RADS in Chinese hospitals was 87.02%. The GDP per capita of the province (P = 0.008), whether the hospital was specialized (P = 0.002) or a Tier 3 facility (P < 0.001), the percentage of doctors with master's and doctoral degrees (P < 0.001) and doctors ≤35 years (P = 0.005) were significantly and independently associated with the utilization rate of BI-RADS. The average diagnostic accuracy rate of breast cancer ultrasound in Chinese hospitals was 73.64%, and we observed significant positive associations between GDP per capita (P = 0.02), BI-RADS utilization rate (P = 0.019), and breast cancer ultrasound diagnostic accuracy. Interpretation: The utilization of BI-RADS templates effectively improved the diagnostic accuracy of ultrasound. Moreover, the survey summarized the current situation of departments and sonologists providing breast ultrasound diagnosis in mainland China, which helped monitor the development of the discipline and provide information for administrators to meet the growing demand. Funding: This work was supported by Natural Science Foundation of Beijing (7202156) and Foundation of ihecc (2019-C-0646-2).

Abstract Background Hepatocellular carcinoma (HCC) is one of the most intractable tumors in the world due to its high rate of recurrence and heterogeneity. Liver cancer initiating cells also called cancer stem cells (CSCs) play a critical role in resistance against typical therapy and high tumor-initiating potential. However, the role of the novel circular RNA (circRNA) circIPO11 in the maintenance of liver cancer initiating cells remains elusive. Methods CircRNAs highly conserved in humans and mice were identified from 3 primary HCC samples by circRNA array. The expression and function of circIPO11 were further evaluated by Northern blot, limiting dilution xenograft analysis, chromatin isolation by RNA purification-PCR assay (ChIRP) and HCC patient-derived tumor cells (PDC) models. CircIpo11 knockout (KO) mice were generated by a CRISPR/Cas9 technology. Results CircIPO11 is highly expressed in HCC tumor tissues and liver CSCs. CircIPO11 is required for the self-renewal maintenance of liver CSCs to initiate HCC development. Mechanistically, circIPO11 recruits TOP1 to GLI1 promoter to trigger its transcription, leading to the activation of Hedgehog signaling. Moreover, GLI1 is also highly expressed in HCC tumor tissues and liver CSCs, and TOP1 expression levels positively correlate with the metastasis, recurrence and survival of HCC patients. Additionally, circIPO11 knockout in mice suppresses the progression of chemically induced liver cancer development. Conclusion Our findings reveal that circIPO11 drives the self-renewal of liver CSCs and promotes the propagation of HCC via activating Hedgehog signaling pathway. Antisense oligonucleotides (ASOs) against circIPO11 combined with TOP1 inhibitor camptothecin (CPT) exert synergistic antitumor effect. Therefore, circIPO11 and the Hedgehog signaling pathway may provide new potential targets for the treatment of HCC patients.

Objective: Neutrophil gelatinase-associated lipocalin (NGAL), a lipocalin, is implicated in many cardiovascular diseases (CVD). The effect of NGAL on endothelial cells (ECs), particularly on ECs injured because of hypoxia, is unclear. In this study, we aim to explore the effect of NGAL in an EC injury in response to hypoxia. Materials and Methods: In this experimental study, we isolated and cultured mouse heart ECs (MHECs). The EC injury model was established by exposure of the ECs to hypoxia for 24 hours. The ECs were treated with NGAL (30, 60, 120, 250 and 500 ng/ml). Cell inflammation and oxidative stress were detected by corresponding assays. Apoptotic cells were stained by the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. Results: NGAL increased the inflammatory response at the baseline level and further augmented the hypoxia-induced inflammation response. Reactive oxygen species (ROS) levels increased upon NGAL treatment, which caused antioxidase/oxidase imbalance. NGAL also exaggerated hypoxia-induced oxidative stress. The cell apoptosis rate also increased in both the NGAL-treated normoxic and hypoxic conditions. NGAL also reduced endothelial nitric oxide synthase (eNOS)-nitric oxide (NO) signalling, thus decreasing the expression and nuclear translocation of nuclear factor erythroid-2-related factor 2 (NRF2), which was confirmed by overexpression of NRF2. Conclusion: NGAL exaggerates EC injury in both normoxic and hypoxic conditions by inhibiting the eNOS-NRF2 pathway.

Summary Gas‐fermenting Clostridium species can convert one‐carbon gases (CO2/CO) into a variety of chemicals and fuels, showing excellent application prospects in green biological manufacturing. The discovery of crucial genes and proteins with novel functions is important for understanding and further optimization of these autotrophic bacteria. Here, we report that the Clostridium ljungdahlii BirA protein (ClBirA) plays a pleiotropic regulator role, which, together with its biotin protein ligase (BPL) activity, enables an effective control of autotrophic growth of C. ljungdahlii. The structural modulation of ClBirA, combined with the in vivo and in vitro analyses, further reveals the action mechanism of ClBirA’s dual roles as well as their interaction in C. ljungdahlii. Importantly, an atypical, flexible architecture of the binding site was found to be employed by ClBirA in the regulation of a lot of essential pathway genes, thereby expanding BirA’s target genes to a broader range in clostridia. Based on these findings, molecular modification of ClBirA was performed, and an improved cellular performance of C. ljungdahlii was achieved in gas fermentation. This work reveals a previously unknown potent role of BirA in gas‐fermenting clostridia, providing new perspective for understanding and engineering these autotrophic bacteria.