A prospective cohort study regarding usability of serum RIPK3 as a biomarker in relation to early hematoma growth and neurological outcomes after acute intracerebral hemorrhage.

OBJECTIVE: The receptor-interacting protein kinase 3 (RIPK3) is a pivotal component for triggering necroptosis. We intended to investigate predictive effects of serum RIPK3 levels on early hematoma growth (EHG) and poor neurological outcome after acute intracerebral hemorrhage (ICH). METHODS: In this prospective cohort study, 183 ICH patients and 100 controls were enrolled for measuring serum RIPK3 levels. National Institutes of Health Stroke Scale (NIHSS) and hematoma volume were recorded as the severity indicators. EHG and poststroke 6-month unfavorable outcome (modified Rankin Scale scores of 3-6) were registered as the two prognostic parameters. Multivariate analyses were implemented to discern relevance of serum RIPK3 to ICH severity and prognosis. RESULTS: Serum RIPK3 levels of patients, which were dramatically higher than those of controls, were independently related to NIHSS scores, hematoma volume, EHG, 6-month mRS scores and unfavorable outcome. Risks of EHG and unfavorable outcome were linearly pertinent to and efficiently discriminated by RIPK3 levels under restricted cubic spline and receiver operating characteristic curve respectively. RIPK3 levels nonsignificantly interacted with age, gender, hypertension, etc. Predictive ability of RIPK3 levels resembled those of NIHSS scores and hematoma volume. The prediction models, in which serum RIPK3, NIHSS scores and hematoma volume were integrated, were visually displayed via nomograms. The models' predictive capabilities substantially surpassed that of serum RIPK3, NIHSS scores and hematoma volumes alone. The models kept stable under calibration curve. CONCLUSION: A profound increase of serum RIPK3 levels after ICH is tightly relevant to severity, EHG and poor neurological outcomes, assuming that serum RIPK3 may emerge as a valuable prognostic predictor of ICH.

Maladaptive regeneration and metabolic dysfunction associated steatotic liver disease: Common mechanisms and potential therapeutic targets.

The normal liver has an extraordinary capacity of regeneration. However, this capacity is significantly impaired in steatotic livers. Emerging evidence indicates that metabolic dysfunction associated steatotic liver disease (MASLD) and liver regeneration share several key mechanisms. Some classical liver regeneration pathways, such as HGF/c-Met, EGFR, Wnt/ß-catenin and Hippo/YAP-TAZ are affected in MASLD. Some recently established therapeutic targets for MASH such as the Thyroid Hormone (TH) receptors, Glucagon-like protein 1 (GLP1), Farnesoid X receptor (FXR), Peroxisome Proliferator-Activated Receptors (PPARs) as well as Fibroblast Growth Factor 21 (FGF21) are also reported to affect hepatocyte proliferation. With this review we aim to provide insight into common molecular pathways, that may ultimately enable therapeutic strategies that synergistically ameliorate steatohepatitis and improve the regenerating capacity of steatotic livers. With the recent rise of prolonged ex-vivo normothermic liver perfusion prior to organ transplantation such treatment is no longer restricted to patients undergoing major liver resection or transplantation, but may eventually include perfused (steatotic) donor livers or even liver segments, opening hitherto unexplored therapeutic avenues.

A Hybrid EEG-Based Stress State Classification Model Using Multi-Domain Transfer Entropy and PCANet.

This paper proposes a new hybrid model for classifying stress states using EEG signals, combining multi-domain transfer entropy (TrEn) with a two-dimensional PCANet (2D-PCANet) approach. The aim is to create an automated system for identifying stress levels, which is crucial for early intervention and mental health management. A major challenge in this field lies in extracting meaningful emotional information from the complex patterns observed in EEG. Our model addresses this by initially applying independent component analysis (ICA) to purify the EEG signals, enhancing the clarity for further analysis. We then leverage the adaptability of the fractional Fourier transform (FrFT) to represent the EEG data in time, frequency, and time-frequency domains. This multi-domain representation allows for a more nuanced understanding of the brain's activity in response to stress. The subsequent stage involves the deployment of a two-layer 2D-PCANet network designed to autonomously distill EEG features associated with stress. These features are then classified by a support vector machine (SVM) to determine the stress state. Moreover, stress induction and data acquisition experiments are designed. We employed two distinct tasks known to trigger stress responses. Other stress-inducing elements that enhance the stress response were included in the experimental design, such as time limits and performance feedback. The EEG data collected from 15 participants were retained. The proposed algorithm achieves an average accuracy of over 92% on this self-collected dataset, enabling stress state detection under different task-induced conditions.

Effects of Cadmium Stress on Tartary Buckwheat Seedlings.

Cadmium (Cd) is a naturally occurring toxic heavy metal that adversely affects plant germination, growth, and development. While the effects of Cd have been described on many crop species including rice, maize, wheat and barley, few studies are available on cadmium's effect on Tartary buckwheat which is a traditional grain in China. We examined nine genotypes and found that 30 µM of Cd reduced the root length in seedlings by between 4 and 44% and decreased the total biomass by 7 to 31%, compared with Cd-free controls. We identified a significant genotypic variation in sensitivity to Cd stress. Cd treatment decreased the total root length and the emergence and growth of lateral roots, and these changes were significantly greater in the Cd-sensitive genotypes than in tolerant genotypes. Cd resulted in greater wilting and discoloration in sensitive genotypes than in tolerant genotypes and caused more damage to the structure of root and leaf cells. Cd accumulated in the roots and shoots, but the concentrations in the sensitive genotypes were significantly greater than in the more tolerant genotypes. Cd treatment affected nutrient uptake, and the changes in the sensitive genotypes were greater than those in the tolerant genotypes, which could maintain their concentrations closer to the control levels. The induction of SOD, POD, and CAT activities in the roots and shoots was significantly greater in the tolerant genotypes than in the sensitive genotypes. We demonstrated that Cd stress reduced root and shoot growth, decreased plant biomass, disrupted nutrient uptake, altered cell structure, and managed Cd-induced oxidative stress differently in the sensitive and tolerant genotypes of Tartary buckwheat.

Impaired Indole Acetic Acid and Reduced Indole-Producing Bacteria Contribute to Swainsonine-Induced Liver Inflammation.

Liver inflammation could be elicited by swainsonine in livestock, affecting the development of agriculture and animal husbandry. Our previous study showed an important role of bile acids (BAs) in swainsonine-induced hepatic inflammation. However, its pathogenesis, particularly the roles of a comprehensive profile of liver and serum metabolites and microbial-derived indole metabolites, has not been clarified. This study aimed to demonstrate the mechanisms linking the indole-producing bacteria and indole metabolites to swainsonine-induced hepatic inflammation by combining Targeted 500 metabolomics and quantitative analysis of indole metabolites. Swainsonine significantly disturbed the liver and serum metabolomes in mice. Genus Akkermansia alleviating inflammation and genus Lactobacillus producing indole metabolites were significantly declined. Indole acetic acid (IAA) was the only reduced aryl hydrocarbon receptor (AHR) ligand in this study. Analogously, some bacteria causing liver damage markedly increased. These findings suggested that indole-producing bacteria and indole metabolites may be potential triggers of swainsonine-induced hepatic inflammation.

Analysis of Drug Resistance Characteristics of Mycobacterium Tuberculosis in Anhui Province, 2016-2022.

Objective: To preliminarily assess the prevalence and control effect of tuberculosis and drug-resistant tuberculosis (TB) in Anhui province, and analyze the trends in the changing drug resistance spectrum of Mycobacterium tuberculosis (Mtb) isolated in Anhui province from 2016 to 2022. Methods: From 2016 to 2022, a total of 2336 culture-positive tuberculosis strains were collected from four drug resistance monitoring sites. Patient demographic information was collected and drug susceptibility testing was conducted. Results: Among the 2336 Mycobacterium tuberculosis complex strains, 1788 (76.54%) were from male patients and 548 (23.46%) were from female patients. The majority were of Han ethnicity, from rural areas, and employed in agriculture, with 12.54% (285/2273) having diabetes. A total of 1893 (81.04%) strains were sensitive to all six anti-TB drugs tested, and 443 (18.96%) strains were resistant to at least one or more anti-TB drugs. The drug resistance rate for patients undergoing initial treatment was 16.80% (348/2071), and 35.85% (95/265) for those receiving retreatment. Among the six anti-TB drugs, the resistance rates from highest to lowest were: INH (10.55%, 236/2336), SM (8.18%, 183/2336), OFX (6.53%, 146/2336), RFP (5.95%, 133/2336), EMB (2.37%, 53/2336), KM (1.97%, 44/2336). Significant differences were observed in MDR strains across different ages, types, with or without diabetes, and geographical sources (χ2=14.895,76.534,6.032,5.109, all P<0.05). Conclusion: The tuberculosis prevention and control measures have controlled the drug resistance rate of Mycobacterium tuberculosis to a certain extent. However, there are still statistical differences in drug resistance rates among TB patients with different categories, age groups, regions, and diabetic diseases. Early detection and prompt treatment of patients with drug-resistant TB remain critical to controlling the spread of this disease.

Genetic factors of grain cadmium concentration in Polish wheat (Triticum polonicum L.).

Wheat (Triticum aestivum L.) is one of the most important crops worldwide and a major source of human Cd intake. Limiting grain Cd concentration (Gr_Cd_Conc) in wheat is necessary to ensure food safety. However, the genetic factors associated with Cd uptake, translocation, distribution, and Gr_Cd_Conc in wheat are poorly understood. Here, we mapped quantitative trait loci (QTL) for Gr_Cd_Conc and its related transport pathway using a recombinant inbred line (RIL_DT) population derived from two Polish wheat varieties (dwarf Polish wheat [DPW] and tall Polish wheat [TPW]). We identified 29 novel major QTLs for grain and tissue Cd concentration; 14 novel major QTLs for Cd uptake, translocation, and distribution; and 27 major QTLs for agronomic traits. We also analyzed the pleiotropy of these QTLs. Six novel QTLs (QGr_Cd_Conc-1A, QGr_Cd_Conc-3A, QGr_Cd_Conc-4B, QGr_Cd_Conc-5B, QGr_Cd_Conc-6A and QGr_Cd_Conc-7A) for Gr_Cd_Conc explained 8.16-17.02% of the phenotypic variation. QGr_Cd_Conc-3A, QGr_Cd_Conc-6A and QGr_Cd_Conc-7A pleiotropically regulated Cd transport; three other QTLs were organ-specific for Gr_Cd_Conc. We fine-mapped the locus of QGr_Cd_Conc-4B and identified the candidate gene as Cation/Ca exchanger 2 (TpCCX2-4B), which was differentially expressed in DPW and TPW. It encodes an endoplasmic reticulum membrane/plasma membrane-localized Cd efflux transporter in yeast. Overexpression of TpCCX2-4B reduced Gr_Cd_Conc in rice. The average Gr_Cd_Conc was significantly lower in TpCCX2-4BDPW genotypes than in TpCCX2-4BTPWgenotypes of the RIL_DT population and two other natural populations, based on a KASP marker derived from the different promoter sequences between TpCCX2-4BDPW and TpCCX2-4BTPW. Our study reveals the genetic mechanism of Cd accumulation in wheat and provides valuable resources for genetic improvement of low-Cd-accumulating wheat cultivars.

Pulse wave signal-driven machine learning for identifying left ventricular enlargement in heart failure patients.

BACKGROUND: Left ventricular enlargement (LVE) is a common manifestation of cardiac remodeling that is closely associated with cardiac dysfunction, heart failure (HF), and arrhythmias. This study aimed to propose a machine learning (ML)-based strategy to identify LVE in HF patients by means of pulse wave signals. METHOD: We constructed two high-quality pulse wave datasets comprising a non-LVE group and an LVE group based on the 264 HF patients. Fourier series calculations were employed to determine if significant frequency differences existed between the two datasets, thereby ensuring their validity. Then, the ML-based identification was undertaken by means of classification and regression models: a weighted random forest model was employed for binary classification of the datasets, and a densely connected convolutional network was utilized to directly estimate the left ventricular diastolic diameter index (LVDdI) through regression. Finally, the accuracy of the two models was validated by comparing their results with clinical measurements, using accuracy and the area under the receiver operating characteristic curve (AUC-ROC) to assess their capability for identifying LVE patients. RESULTS: The classification model exhibited superior performance with an accuracy of 0.91 and an AUC-ROC of 0.93. The regression model achieved an accuracy of 0.88 and an AUC-ROC of 0.89, indicating that both models can quickly and accurately identify LVE in HF patients. CONCLUSION: The proposed ML methods are verified to achieve effective classification and regression with good performance for identifying LVE in HF patients based on pulse wave signals. This study thus demonstrates the feasibility and potential of the ML-based strategy for clinical practice while offering an effective and robust tool for diagnosing and intervening ventricular remodeling.

Identification and Characterization of LBD Gene Family in Pseudoroegneria libanotica Reveals Functions of PseLBD1 and PseLBD12 in Response to Abiotic Stress.

The lateral organ boundaries domain (LBD) plays a vital role as a transcriptional coactivator within plants, serving as an indispensable function in growth, development, and stress response. In a previous study, we found that the LBD genes of Pseudoroegneria libanotica (a maternal donor for three-quarter of perennial Triticeae species with good stress resistance, holds great significance in exploring its response mechanisms to abiotic stress for the Triticeae tribe) might be involved in responding to drought stress. Therefore, we further identified the LBD gene family in this study. A total of 29 PseLBDs were identified. Among them, 24 were categorized into subclass I, while 5 fell into subclass II. The identification of cis-acting elements reveals the extensive involvement of PseLBDs in various biological processes in P. libanotica. Collinearity analysis indicates that 86% of PseLBDs were single-copy genes and have undergone a single whole-genome duplication event. Transcriptomic differential expression analysis of PseLBDs under drought stress reveals that the most likely candidates for responding to abiotic stress were PseLBD1 and PseLBD12. They have been demonstrated to respond to drought, salt, heavy metal, and heat stress in yeast. Furthermore, it is plausible that functional divergence might have occurred among their orthologous genes in wheat. This study not only establishes a foundation for a deeper understanding of the biological roles of PseLBDs in P. libanotica but also unveils novel potential genes for enhancing the genetic background of crops within Triticeae crops, such as wheat.

Case report: A healthy baby achieved after preimplantation genetic testing from an infertile woman with hereditary leiomyomatosis and renal cell cancer syndrome.

Background: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant inheritable disease caused by Fumarate hydratase (FH) gene germline mutation. It is speculated that for HRLCC infertility women with multiple uterine leiomyomas, preimplantation genetic testing may help block transmission of mutated FH gene during pregnancy. Case presentation: We present the case of a 26-year-old nulligravida with a history of early-onset uterine leiomyomatosis had a heterozygous nonsense mutation [NM_000143.4 (FH): c.1027C > T(p.Arg343Ter)] in the HRLLC gene. After ovulation induction and in vitro fertilization, preimplantation genetic testing for monogenic disorders (PGT-M) on embryos revealed the absence of the pathogenic allele in two blastomeres. Uterine fibroids were identified before embryo transfer, leading to a submucosal myomectomy and long period of pituitary suppression by Gonadotropin-releasing hormone analog (GnRHa). The patient achieved a healthy live birth after the second cycle of frozen-thawed embryo transfer. Conclusion: This case details the successful treatment of an infertile patient with an HRLLC family history, resulting in a healthy birth through myomectomy and PGT-M selected embryo transplantation. Our literature search indicates the first reported live birth after HRLLC-PGT-M.

ANGPTL3 diminishes the resistance of ovarian cancer to paclitaxel by blocking the PI3K-AKT-mTOR signaling pathway.

Angiopoietin-like protein 3 (ANGPTL3) is key in ovarian cancer (OC) cell growth and metastasis, notably by enhancing natural killer cells' capacity for inducing cell toxicity and apoptosis. However, its role in influencing chemotherapy resistance in OC remains ambiguous. In this study, we discovered a correlation between reduced ANGPTL3 levels and a less favorable outcome in OC patients using the Kaplan-Meier Plotter database. Lower levels of ANGPTL3 were detected in paclitaxel (PTX)-resistant OC tissues and cell lines via western blotting and immunohistochemistry. To investigate ANGPTL3's effects, we established SKOV3/PTX and 2780/PTX as PTX-resistant OC cell lines by incrementally increasing PTX exposure and then transfecting them with overexpress ANGPTL3 (OE-ANGPTL3) lentivirus. We conducted various assays such as CCK-8, colony formation, Edu staining, flow cytometry, and transwell to investigate the impact of ANGPTL3 on PTX resistance. Additionally, this effect was examined in a mouse subcutaneous xenograft model. Both in vitro and in vivo experiments demonstrated that ANGPTL3 overexpression mitigated PTX resistance in OC cells by inactivating the PI3K-AKT-mTOR pathway. In summary, our research reveals that ANGPTL3 enhances PTX sensitivity in OC by downregulating the PI3K-AKT-mTOR pathway. The study of this study suggest that ANGPTL3 could serve as a valuable therapeutic target for OC, signifying its clinical relevance in OC management.

Role of tcaA, a potential target as a ceftobiprole resistance breaker in MRSA ß-lactam resistance.

OBJECTIVES: Using a random forest algorithm, we previously found that teicoplanin-associated gene A (tcaA) might play a role in resistance of methicillin-resistant Staphylococcus aureus (MRSA) to ß-lactams, which we have investigated further here. METHODS: Representative MRSA strains of prevalent clones were selected to identify the role of tcaA in the MRSA response to ß-lactams. tcaA genes were deleted by homologous recombination in the selected MRSA strains, and antibiotic susceptibility tests were applied to evaluate the effect of tcaA on the minimum inhibitory concentrations (MICs) of glycopeptides and ß-lactams. Scanning electron microscopy, RNA sequencing, and quantitative reverse transcription-polymerase chain reaction were performed to explore the mechanism of tcaA in MRSA resistance to ß-lactams. RESULTS: The MIC of penicillin plus clavulanate decreased from 3 mg/L to 0.064 mg/L and that of oxacillin decreased from 16 to 0.5 mg/L when tcaA was knocked out in the LAC strain. Compared with wild-type MRSA isolates, when tcaA was deleted, all selected strains were more susceptible to ß-lactams. Susceptibility to ceftobiprole was restored in the ceftobiprole-resistant strain when tcaA was deleted. tcaA knockout caused "log-like" abnormal division of MRSA, and tcaA deficiency mediated low expression of mecA, ponA, and murA2. CONCLUSIONS: Machine learning is a reliable tool for identifying drug resistance-related genes. tcaA may be involved in S. aureus cell division and may affect mecA, ponA, and murA2 expression. Furthermore, tcaA is a potential resistance breaker target for ß-lactams, including ceftobiprole, in MRSA.

The Relationship Between Cardiac CT-based Left Atrial Structure and Epicardial Adipose Tissue and Postablation Atrial Fibrillation Recurrence Within 2 Years.

PURPOSE: The aim of this study was to explore the association of cardiac CT-based left atrium (LA) structural and functional parameters and left atrial epicardial adipose tissue (LA-EAT) parameters with postablation atrial fibrillation (AF) recurrence within 2 years. MATERIALS AND METHODS: Contrast-enhanced cardiac CT images of 286 consecutive AF patients (median age: 65 y; 97 females) who underwent initial ablation between June 2018 and June 2020 were retrospectively analyzed. Structural and functional parameters of LA, including maximum and minimum volume and ejection fraction of LA and left atrial appendage (LAA), and LA-EAT volume, were measured. The body surface area indexed maximum and minimum volume of LA (LAVImax, LAVImin) and LAA (LAAVImax, LAAVImin), and LA-EAT volume index (LA-EATVI) were calculated. Independent predictors of AF recurrence were determined using Cox regression analysis. The clinical predictors were added to the imaging predictors to build a combined model (clinical+imaging). The predictive performance of the clinical, imaging, and combined models was assessed using the area under the receiver operating characteristics curve (AUC). RESULTS: A total of 108 (37.8%) patients recurred AF within 2 years after ablation at a median follow-up of 24 months (IQR=11, 32). LA and LAA size and LA-EAT volume were significantly increased in patients with AF recurrence (P<0.05). After the multivariable regression analysis, LA-EATVI, LAAVImax, female sex, AF duration, and stroke history were independent predictors for AF recurrence. The combined model exhibited superior predictive performance compare to the clinical model (AUC=0.712 vs. 0.641, P=0.023) and the imaging model (AUC=0.712 vs. 0.663, P=0.018). CONCLUSION: Cardiac CT-based LA-EATVI and LAAVImax are independent predictors for postablation AF recurrence within 2 years and may provide a complementary value for AF recurrence risk assessment.

Defects and Defect Passivation in Perovskite Solar Cells.

Perovskite solar cells have made significant strides in recent years. However, there are still challenges in terms of photoelectric conversion efficiency and long-term stability associated with perovskite solar cells. The presence of defects in perovskite materials is one of the important influencing factors leading to subpar film quality. Adopting additives to passivate defects within perovskite materials is an effective approach. Therefore, we first discuss the types of defects that occur in perovskite materials and the mechanisms of their effect on performance. Then, several types of additives used in perovskite solar cells are discussed, including ionic compounds, organic molecules, polymers, etc. This review provides guidance for the future development of more sustainable and effective additives to improve the performance of solar cells.

Identification of candidate genes for adult plant stripe rust resistance transferred from Aegilops ventricosa 2NvS into wheat via fine mapping and transcriptome analysis.

KEY MESSAGE: An adult plant gene for resistance to stripe rust was narrowed down to the proximal one-third of the 2NvS segment translocated from Aegilops ventricosa to wheat chromosome arm 2AS, and based on the gene expression analysis, two candidate genes were identified showing a stronger response at the adult plant stage compared to the seedling stage. The 2NvS translocation from Aegilops ventricosa, known for its resistance to various diseases, has been pivotal in global wheat breeding for more than three decades. Here, we identified an adult plant resistance (APR) gene in the 2NvS segment in wheat line K13-868. Through fine mapping in a segregating near-isogenic line (NIL) derived population of 6389 plants, the candidate region for the APR gene was narrowed down to between 19.36 Mb and 33 Mb in the Jagger reference genome. Transcriptome analysis in NILs strongly suggested that this APR gene conferred resistance to stripe rust by triggering plant innate immune responses. Based on the gene expression analysis, two disease resistance-associated genes within the candidate region, TraesJAG2A03G00588940 and TraesJAG2A03G00590140, exhibited a stronger response to Puccinia striiformis f. sp. tritici (Pst) infection at the adult plant stage than at the seedling stage, indicating that they could be potential candidates for the resistance gene. Additionally, we developed a co-dominant InDel marker, InDel_31.05, for detecting this APR gene. Applying this marker showed that over one-half of the wheat varieties approved in 2021 and 2022 in Sichuan province, China, carry this gene. Agronomic trait evaluation of NILs indicated that the 2NvS segment effectively mitigated the negative effects of stripe rust on yield without affecting other important agronomic traits. This study provided valuable insights for cloning and breeding through the utilization of the APR gene present in the 2NvS segment.

Meta-analysis of the relationship between ocular and peripheral serum IL-17A and diabetic retinopathy.

Purpose: A systematic evaluation and Meta-analysis were performed to determine the relationship between IL-17A levels in ocular aqueous and peripheral venous serum samples and diabetic retinopathy (DR). Methods: PubMed, Embase, Web of Science, and CNKI databases were searched from the time of library construction to 2023-09-20.The results were combined using a random-effects model, sensitivity analyses were performed to determine whether the arithmetic was stable and reliable, and subgroup analyses were used to look for possible sources of heterogeneity. Results: A total of 7 case-control studies were included. The level of IL-17A was higher in the Nonproliferative DR(NPDR) group than in the Non-DR(NDR) group [SMD=2.07,95%CI(0.45,3.68),P=0.01], and the level of IL-17A in the proliferating DR(PDR) group was higher than that of the NDR group [SMD=4.66,95%CI(1.23,8.08),P<0.00001]. IL-17A levels in peripheral serum and atrial fluid were significantly higher in NPDR and PDR patients than in non-DR patients in subgroup analyses, and detection of peripheral serum IL-17A concentrations could help to assess the risk of progression from NPDR to PDR. Sensitivity analyses suggested that the results of the random-effects arithmetic were stable and reliable. Subgroup analyses based on assay method and sample source showed that the choice of these factors would largely influence the relationship between IL-17A levels and DR. Conclusion: Elevated peripheral serum and ocular aqueous humor IL-17A levels in diabetic patients are associated with the risk of DR, IL-17A may serve as a potential predictor or therapeutic target for DR, and IL-17A may be an important predictor of inflammation for the progression of NPDR to PDR. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024532900.

ACSL4 promotes malignant progression of Hepatocellular carcinoma by targeting PAK2 transcription.

Long-chain fatty acyl-Coa ligase 4 (ACSL4) is an important enzyme that converts fatty acids to fatty acyl-Coa esters, there is increasing evidence for its role in carcinogenesis. However, the precise role of ACLS4 in hepatocellular carcinoma (HCC) is not clearly understood. In the present study, we provide evidence that ACSL4 expression was specifically elevated in HCC and is associated with poor clinical outcomes. ACSL4 significantly promotes the growth and metastasis of HCC both in vitro and in vivo. RNA sequencing and functional experiments showed that the effect of ACSL4 on HCC development was heavily dependent on PAK2. ACSL4 expression is well correlated with PAK2 in HCC, and ACSL4 even transcriptionally increased PAK2 gene expression mediated by Sp1. In addition, emodin, a naturally occurring anthraquinone derivative, inhibited HCC cell growth and tumor progression by targeting ACSL4. In summary, ACSL4 plays a novel oncogene in HCC development by regulating PAK2 transcription. Targeting ACSL4 could be useful in drug development and therapy for HCC.

Unconventional Activation of IRE1 Enhances TH17 Responses and Promotes Airway Neutrophilia.

Heightened unfolded protein responses (UPRs) are associated with the risk for asthma, including severe asthma. Treatment-refractory severe asthma manifests a neutrophilic phenotype with TH17 responses. However, how UPRs participate in the deregulation of TH17 cells leading to neutrophilic asthma remains elusive. This study found that the UPR sensor IRE1 is induced in the murine lung with fungal asthma and is highly expressed in TH17 cells relative to naïve CD4+ T cells. Cytokine (e.g. IL-23) signals induce the IRE1-XBP1s axis in a JAK2-dependent manner. This noncanonical activation of the IRE1-XBP1s pathway promotes UPRs and cytokine secretion by both human and mouse TH17 cells. Ern1 (encoding IRE1)-deficiency decreases the expression of ER stress factors and impairs the differentiation and cytokine secretion of TH17 cells. Genetic ablation of Ern1 leads to alleviated TH17 responses and airway neutrophilia in a fungal airway inflammation model. Consistently, IL-23 activates the JAK2-IRE1-XBP1s pathway in vivo and enhances TH17 responses and neutrophilic infiltration into the airway. Taken together, our data indicate that IRE1, noncanonically activated by cytokine signals, promotes neutrophilic airway inflammation through the UPR-mediated secretory function of TH17 cells. The findings provide a novel insight into the fundamental understanding of IRE1 in TH17-biased TH2-low asthma.

Genome-wide identification of bHLH transcription factors and expression analysis under drought stress in Pseudoroegneria libanotica at germination.

The basic helix-loop-helix (bHLH) transcription factor family is the second largest in plants. bHLH transcription factor is not only universally involved in plant growth and metabolism, including photomorphogenesis, light signal transduction, and secondary metabolism, but also plays an important role in plant response to stress. However, the function of bHLH TFs in Pseudoroegneria species has not been studied yet. Pseudoroegneria (Nevski) Á. Löve is a perennial genus of the Triticeae. Pseudoroegneria species are mostly distributed in arid/semi-arid areas and they show good drought tolerance. In this study, we identified 152 PlbHLH TFs in Pseudoroegneria libanotica, which could be classified into 15 groups. Collinearity analysis indicates that 122 PlbHLH genes share homology with wbHLH genes in wheat, and it has lower homology with AtbHLH genes in Arabidopsis. Based on transcriptome profiling under an experiment with three PEG concentrations (0%, 10%, and 20%), 10 up-regulated genes and 11 down-regulated PlbHLH genes were screened. Among them, PlbHLH6, PlbHLH55 and PlbHLH64 as candidate genes may be the key genes related to drought tolerance response at germination, and they have been demonstrated to respond to drought, salt, oxidative, heat, and heavy metal stress in yeast. This study lays the foundation for an in-depth study of the biological roles of PlbHLHs in Pse. libanotica, and discovered new drought-tolerance candidate genes to enhance the genetic background of Triticeae crops. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01433-w.

Effect of ultrasonic power on delivery of quercetin in emulsions stabilized using octenyl succinic anhydride (OSA) modified broken japonica rice starch.

In this study, emulsions stabilized by octenyl succinic anhydride-modified broken japonica rice starch (OSA-BJRS) were prepared at different ultrasonic power intensities for the delivery, controlled release, and improved bioavailability of quercetin. The OSA-BJRS emulsions ultrasonicated at 400 W exhibited the highest encapsulation efficiency (89.37 %) and loading efficiency (58.34 %) of quercetin, the smallest volume-average droplet diameter (0.51 µm) and polydispersity index (0.19), the highest absolute value of the ζ-potential (26.73 mV), and the highest apparent viscosity and viscoelasticity. The oxidation stability, storage stability, thermal stability, and salt ion stability of the emulsions were also notably improved by the ultrasonication treatment. In addition, the results of the simulated in vitro digestion demonstrated that the ultrasonicated OSA-BJRS emulsions had an enhanced quercetin delivery performance and could stably transport quercetin to the small intestine for digestion. The OSA-BJRS emulsion ultrasonicated at 400 W exhibited the highest cumulative release rate (95.91 %) and the highest bioavailability (30.48 %) of quercetin. This suggests that OSA-BJRS emulsions prepared by ultrasonication can be considered effective delivery systems for hydrophobic functional components.