Acetylation of transcription factor BpTCP20 by acetyltransferase BpPDCE23 modulates salt tolerance in birch.

Teosinte branched 1/Cycloidea/Proliferating cell factor (TCP) transcription factors function in abiotic stress responses. However, how TCPs confer salt tolerance is unclear. Here, we characterized a TCP transcription factor, BpTCP20, that responds to salt stress in birch (Betula platyphylla Suk). Plants overexpressing BpTCP20 displayed increased salt tolerance, and Bptcp20 knockout mutants displayed reduced salt tolerance relative to the wild-type (WT) birch. BpTCP20 conferred salt tolerance by mediating stomatal closure and reducing reactive oxygen species (ROS) accumulation. Chromatin immunoprecipitation sequencing showed that BpTCP20 binds to NeuroD1, T-box, and two unknown elements (termed TBS1 and TBS2) to regulate target genes. In birch, salt stress led to acetylation of BpTCP20 acetylation at lysine 259. A mutated BpTCP20 variant (abolished for acetylation, termed BpTCP20259) was overexpressed in birch, which led to decreased salt tolerance compared with plants overexpressing BpTCP20. However, BpTCP20259-overexpressing plants still displayed increased salt tolerance relative to untransformed WT plants. BpTCP20259 showed reduced binding to the promoters of target genes and decreased target gene activation, leading to decreased salt tolerance. In addition, we identified dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex (BpPDCE23), an acetyltransferase that interacts with and acetylates BpTCP20 to enhance its binding to DNA motifs. Together, these results suggest that BpTCP20 is a transcriptional regulator of salt tolerance, whose activity is modulated by BpPDCE23-mediated acetylation.

Associations between liver function and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in non-demented adults: The CABLE study.

Liver function has been suggested as a possible factor in the progression of Alzheimer's disease (AD) development. However, the association between liver function and cerebrospinal fluid (CSF) levels of AD biomarkers remains unclear. In this study, we analyzed the data from 1687 adults without dementia from the Chinese Alzheimer's Biomarker and LifestylE study to investigate differences in liver function between pathological and clinical AD groups, as defined by the 2018 National Institute on Aging-Alzheimer's Association Research Framework. We also examined the linear relationship between liver function, CSF AD biomarkers, and cognition using linear regression models. Furthermore, mediation analyses were applied to explore the potential mediation effects of AD pathological biomarkers on cognition. Our findings indicated that, with AD pathological and clinical progression, the concentrations of total protein (TP), globulin (GLO), and aspartate aminotransferase/alanine transaminase (ALT) increased, while albumin/globulin (A/G), adenosine deaminase, alpha-L-fucosidase, albumin, prealbumin, ALT, and glutamate dehydrogenase (GLDH) concentrations decreased. Furthermore, we also identified significant relationships between TP (ß = -0.115, pFDR < 0.001), GLO (ß = -0.184, pFDR < 0.001), and A/G (ß = 0.182, pFDR < 0.001) and CSF ß-amyloid1-42 (Aß1-42 ) (and its related CSF AD biomarkers). Moreover, after 10 000 bootstrapped iterations, we identified a potential mechanism by which TP and GLDH may affect cognition by mediating CSF AD biomarkers, with mediation effect sizes ranging from 3.91% to 16.44%. Overall, our results suggested that abnormal liver function might be involved in the clinical and pathological progression of AD. Amyloid and tau pathologies also might partially mediate the relationship between liver function and cognition. Future research is needed to fully understand the underlying mechanisms and causality to develop an approach to AD prevention and treatment approach.

Associations of liver dysfunction with incident dementia, cognition, and brain structure: A prospective cohort study of 431 699 adults.

The relationship between liver dysfunction and dementia has been researched extensively but remains poorly understood. In this study, we investigate the longitudinal and cross-sectional associations between liver function and liver diseases and risk of incident dementia, impaired cognition, and brain structure abnormalities using Cox proportion hazard model and linear regression model. 431 699 participants with a mean of 8.65 (standard deviation [SD] 2.61) years of follow-up were included from the UK Biobank; 5542 all-cause dementia (ACD), 2427 Alzheimer's disease (AD), and 1282 vascular dementia (VaD) cases were documented. We observed that per SD decreases in alanine transaminase (ALT; hazard ratio [HR], 0.917; PFDR <0.001) and per SD increases in aspartate aminotransferase (AST; HR, 1.048; PFDR = 0.010), AST to ALT ratio (HR, 1.195; PFDR <0.001), gamma-glutamyl transpeptidase (GGT; HR, 1.066; PFDR <0.001), alcoholic liver disease (ALD; HR, 2.872; PFDR <0.001), and fibrosis and cirrhosis of liver (HR, 2.285; PFDR = 0.002), being significantly associated with a higher risk of incident ACD. Restricted cubic spline models identified a strong U-shaped association between Alb and AST and incident ACD (Pnonlinear <0.05). Worse cognition was positively correlated with AST, AST to ALT ratio, direct bilirubin (DBil), and GGT; negatively correlated with ALT, Alb, and total bilirubin (TBil); and ALD and fibrosis and cirrhosis of liver (PFDR <0.05). Moreover, changes in ALT, GGT, AST to ALT ratio, and ALD were significantly associated with altered cortical and subcortical regions, including hippocampus, amygdala, thalamus, pallidum, and fusiform (PFDR <0.05). In sensitivity analysis, metabolic dysfunction-associated steatotic liver disease (MASLD) was associated with the risk of ACD and brain subcortical changes. Our findings provide substantial evidence that liver dysfunction may be an important factor for incident dementia. Early intervention in the unhealthy liver may help prevent cognitive impairment and dementia incidence.

A Review of Bioactive Compound Effects from Primary Legume Protein Sources in Human and Animal Health.

The global demand for sustainable and nutritious food sources has catalyzed interest in legumes, known for their rich repertoire of health-promoting compounds. This review delves into the diverse array of bioactive peptides, protein subunits, isoflavones, antinutritional factors, and saponins found in the primary legume protein sources-soybeans, peas, chickpeas, and mung beans. The current state of research on these compounds is critically evaluated, with an emphasis on the potential health benefits, ranging from antioxidant and anticancer properties to the management of chronic diseases such as diabetes and hypertension. The extensively studied soybean is highlighted and the relatively unexplored potential of other legumes is also included, pointing to a significant, underutilized resource for developing health-enhancing foods. The review advocates for future interdisciplinary research to further unravel the mechanisms of action of these bioactive compounds and to explore their synergistic effects. The ultimate goal is to leverage the full spectrum of benefits offered by legumes, not only to advance human health but also to contribute to the sustainability of food systems. By providing a comprehensive overview of the nutraceutical potential of legumes, this manuscript sets a foundation for future investigations aimed at optimizing the use of legumes in the global pursuit of health and nutritional security.

A reverse chromatin immunoprecipitation technique based on the CRISPR-dCas9 system.

DNA-protein interaction is one of the most crucial interactions in biological processes. However, the technologies available to study DNA-protein interactions are all based on DNA hybridization; however, DNA hybridization is not highly specific and is relatively low in efficiency. RNA-guided DNA recognition is highly specific and efficient. To overcome the limitations of technologies based on DNA hybridization, we built a DNA-binding protein capture technology based on the clustered regularly interspaced palindromic repeats (CRISPR)-dead Cas9 (dCas9) system and transient genetic transformation, termed reverse chromatin immunoprecipitation based on CRISPR-dCas9 system (R-ChIP-dCas9). In this system, dCas9 was fused with Strep-Tag II to form a fusion protein for StrepTactin affinity purification. Transient transformation was performed for the expression of dCas9 and guide RNA (gRNA) to form the dCas9-gRNA complex in birch (Betula platyphylla) plants, which binds to the target genomic DNA region. The dCas9-gRNA-DNA complex was crosslinked, then the chromatin was sonicated into fragments, and purified using StrepTactin beads. The proteins binding to the target genomic DNA region were identified using mass spectrometry. Using this method, we determined the upstream regulators of a NAM, ATAF, and CUC (NAC) transcription factor (TF), BpNAC090, and 32 TFs potentially regulating BpNAC090 were identified. The reliability of R-ChIP-dCas9 was further confirmed by chromatin immunoprecipitation, electrophoretic mobility shift assays, and yeast one-hybrid. This technology can be adapted to various plant species and does not depend on the availability of a stable transformation system; therefore, it has wide application in identifying proteins bound to genomic DNA.

Distinct impacts of radiological appearance on lymph node metastasis and prognosis based on solid size in clinical T1 non-small cell lung cancer.

BACKGROUND: Solid nodules (SN) had more aggressive features and a poorer prognosis than part-solid nodules (PSN). This study aimed to evaluate the specific impacts of nodule radiological appearance (SN vs. PSN) on lymph node metastasis and prognosis based on solid size in cT1 non-small cell lung cancer (NSCLC). METHODS: Patients with cT1 NSCLC who underwent anatomical resection between 2010 and 2019 were retrospectively screened. Univariable and multivariable logistic regression analyses were adopted to evaluate the associations between nodule radiological appearance and lymph node metastasis. The log-rank test and Cox regression analyses were applied for prognostic evaluation. The cumulative recurrence risk was evaluated by the competing risk model. RESULTS: There were 958 and 665 NSCLC patients with PSN and SN. Compared to the PSN group, the SN arm had a higher overall lymph node metastasis rate (21.7% vs. 2.7%, P < 0.001), including nodal metastasis at N1 stations (17.7% vs. 2.1%), N2 stations (14.0% vs. 1.6%), and skip nodal metastasis (3.9% vs. 0.6%). However, for cT1a NSCLC, no significant difference existed between SN and PSN (0 vs. 0.4%, P = 1). In addition, the impacts of nodule radiological appearance on lymph node metastasis varied between nodal stations. Solid NSCLC had an inferior prognosis than part-solid patients (5-year disease-free survival: 79.3% vs. 96.2%, P < 0.001). The survival inferiority only existed for cT1b and cT1c NSCLC, but not for cT1a. Strikingly, even for patients with nodal involvement, SN still had a poorer disease-free survival (P = 0.048) and a higher cumulative incidence of recurrence (P < 0.001) than PSN. Specifically, SN had a higher recurrence risk than PSN at each site. Nevertheless, the distribution of recurrences between SN and PSN was similar, except that N2 lymph node recurrences were more frequent in solid NSCLC (28.21% vs. 7.69%, P = 0.041). CONCLUSION: SN had higher risks of lymph node metastasis and poorer prognosis than PSN for cT1b and cT1c NSCLC, but not for cT1a. SN exhibited a greater proportion of N2 lymph node recurrence than PSN. SN and PSN needed distinct strategies for nodal evaluation and postoperative follow-up.

Identification and functional marker development of SbPLSH1 conferring purple leaf sheath in sorghum.

KEY MESSAGE: We identified a SbPLSH1gene conferring purple leaf sheath in sorghum (sorghumbicolor(L.) Moench)and developed a functional markerfor it. The purple leaf sheath of sorghum, a trait mostly related to anthocyanin deposition, is a visually distinguishable morphological marker widely used to evaluate the purity of crop hybrids. We aimed to dissect the genetic mechanism for leaf sheath color to mine the genes regulating this trait. In this study, two F2 populations were constructed by crossing a purple leaf sheath inbred line (Gaoliangzhe) with two green leaf sheath inbred lines (BTx623 and Silimei). Based on the results of bulked-segregant analysis sequencing, bulk-segregant RNA sequencing, and map-based cloning, SbPLSH1 (Sobic.006G175700), which encodes a bHLH transcription factor on chromosome 6, was identified as the candidate gene for purple leaf sheath in sorghum. Genetic analysis demonstrated that overexpression of SbPLSH1 in Arabidopsis resulted in anthocyanin deposition and purple petiole, while two single-nucleotide polymorphism (SNP) variants on the exon 6 resulted in loss of function. Further haplotype analysis revealed that there were two missense mutations and one cis-acting element mutation in SbPLSH1, which are closely associated with leaf sheath color in sorghum. Based on the variations, a functional marker (LSC4-2) for marker-assisted selection was developed, which has a broad-spectrum capability of distinguishing leaf sheath color in natural variants. In summary, this study lays a foundation for analyzing the genetic mechanism for sorghum leaf sheath color.

The key pathways for drought tolerance in Cerasus humilis were unveiled through transcriptome analysis.

Drought stress exerts a significant impact on the growth, development, and yield of fruit trees. Cerasus humilis is an endemic drought-resistant fruit tree in northern China. To elucidate the underlying mechanism of drought resistance in C. humilis, comprehensive physiological measurements and transcriptome analysis were conducted on the leaves of C. humilis subjected to 15- or 22-days of drought stress. We identified multiple GO terms and KEGG pathways associated with the drought stress response by performing GO and KEGG analysis on DEGs. Furthermore, through the prediction of transcription factors (TFs) and analysis of their expression levels, we observed differential expression patterns among most members of stress-responsive TF families as the duration of drought stress increased. WGCNA analysis was performed on the transcriptome to identify gene cluster modules that exhibited a strong correlation with the durations of drought. Subsequently, these modules underwent GO and KEGG enrichment analyses. The study revealed that the TF-mediated lignin biosynthesis pathway, along with the plant hormone signal transduction pathway, played a prominent role in responding to drought stress of C. humilis. Gene profiling analysis, qRT-PCR, and determination of phytohormone and lignin contents further supported this hypothesis. The hierarchical gene regulatory network was finally constructed based on DEGs from the aforementioned key enriched pathways to predict the gene regulatory mechanisms in response to stress for C. humilis. The findings from this study provide valuable insights into how C. humilis copes with drought stress while analyzing crucial gene pathways associated with its resistance from a TF perspective. This research is significant for the genetic breeding of economic forests.

Decoding active compounds and molecular targets of herbal medicine by high-throughput metabolomics technology: A systematic review.

Clinical experiences of herbal medicine (HM) have been used to treat a variety of human intractable diseases. As the treatment of diseases using HM is characterized by multi-components and multi-targets, it is difficult to determine the bio-active components, explore the molecular targets and reveal the mechanisms of action. Metabolomics is frequently used to characterize the effect of external disturbances on organisms because of its unique advantages on detecting changes in endogenous small-molecule metabolites. Its systematicity and integrity are consistent with the effective characteristics of HM. After HM intervention, metabolomics can accurately capture and describe the behavior of endogenous metabolites under the disturbance of functional compounds, which will be used to decode the bioactive ingredients of HM and expound the molecular targets. Metabolomics can provide an approach for explaining HM, addressing unclear clinical efficacy and undefined mechanisms of action. In this review, the metabolomics strategy and its applications in HM are systematically introduced, which offers valuable insights for metabolomics methods to characterizing the pharmacological effects and molecular targets of HM.

Effect of apheresis plasma donation on plasma uric acid levels, the lipid profile, and major plasma proteins in plasma donors in China: A multicenter, prospective cohort study.

Abnormal plasma uric acid (UA) levels, the lipid profile, and plasma proteins in blood are associated with a range of adverse health outcomes. This multicenter, prospective cohort study aimed to determine the possible effects of multiple apheresis plasma donations on plasma UA levels, the lipid profile, and major proteins in plasma donors. Participants were enrolled from 1 April 2021 to 31 August 2022. When their plasma UA (men: >420 µmol/L, women: >360 µmol/L) and/or lipid levels (total cholesterol [TC]: ≥6.2 mmol/L, triglycerides [TGs]: ≥2.3 mmol/L, low-density lipoprotein cholesterol: ≥4.1 mmol/L, or high-density lipoprotein cholesterol [HDL-C]: <1.0 mmol/L) were abnormal at their first plasma donation, the enrolled participants were followed up until they had completed 10 plasma donations. A total of 11485 participants were enrolled, of whom 1861 met the inclusion criteria. During the study period, 320 donors completed 10 plasma donations. None of the participants took any corrective medicine for their abnormal index. The measured parameters were significantly different from the first to the tenth plasma donations (donors with asymptomatic hyperuricemia: UA, P < 0.001; donors with asymptomatic hyperlipidemia: HDL-C, P < 0.001; TC, P = 0.025; TGs, P < 0.001; apolipoprotein B, P = 0.025; all of the plasma donors, immunoglobulin G, P < 0.001). The levels of HDL-C, TC, and apolipoprotein B were increased, and the levels of UA, TGs, and immunoglobulin G were decreased over this time. However, immunoglobulin G levels were still in the normal range. Moreover, the changes in these parameters were closely associated with the frequency of plasma donation during the study period. Repeated apheresis plasma donations can reduce plasma UA and TG levels and increase HDL-C levels; and further evaluation of the clinical significance with a larger sample size is required.

Metabolomics for Clinical Biomarker Discovery and Therapeutic Target Identification.

As links between genotype and phenotype, small-molecule metabolites are attractive biomarkers for disease diagnosis, prognosis, classification, drug screening and treatment, insight into understanding disease pathology and identifying potential targets. Metabolomics technology is crucial for discovering targets of small-molecule metabolites involved in disease phenotype. Mass spectrometry-based metabolomics has implemented in applications in various fields including target discovery, explanation of disease mechanisms and compound screening. It is used to analyze the physiological or pathological states of the organism by investigating the changes in endogenous small-molecule metabolites and associated metabolism from complex metabolic pathways in biological samples. The present review provides a critical update of high-throughput functional metabolomics techniques and diverse applications, and recommends the use of mass spectrometry-based metabolomics for discovering small-molecule metabolite signatures that provide valuable insights into metabolic targets. We also recommend using mass spectrometry-based metabolomics as a powerful tool for identifying and understanding metabolic patterns, metabolic targets and for efficacy evaluation of herbal medicine.

Negative energy balance affects perinatal ewe performance, rumen morphology, rumen flora structure, and placental function.

This study investigated the effects of negative energy balance (NEB) on perinatal ewes, with a focus on changes in growth performance, serum biochemical parameters, rumen fermentation, ruminal bacteria composition, placental phenotype-related indicators, and expression levels of genes related to placental function. Twenty ewes at 130 days of gestation were randomly allocated to either the positive energy balance (PEB) or NEB groups. In the experiment, ewes in the PEB group were fed the same amount as their intake during the pre-feeding baseline period, while ewes in the NEB group were restricted to 70% of their individual baseline feed intake. The experiment was conducted until 42 days postpartum, and five double-lamb ewes per group were selected for slaughter. The results demonstrated that NEB led to a significant decrease in body weight, carcass weight, and the birth and weaning weights of lambs (P < 0.05). Additionally, NEB caused alterations in serum biochemical parameters, such as increased non-esterified fatty acids and ß-hydroxybutyrate levels and decreased cholesterol and albumin levels (P < 0.05). Rumen fermentation and epithelial parameters were also affected, with a reduction in the concentrations of acetic acid, butyric acid, total acid and a decrease in the length of the rumen papilla (P < 0.05). Moreover, NEB induced changes in the structure and composition of ruminal bacteria, with significant differences in α-diversity indices and rumen microbial community composition (P < 0.05). Gene expression in rumen papilla and ewe placenta was also affected, impacting genes associated with glucose and amino acid transport, proliferation, apoptosis, and angiogenesis (P < 0.05). These findings screened the key microbiota in the rumen of ewes following NEB and highlighted the critical genes associated with rumen function. Furthermore, this study revealed the impact of NEB on placental function in ewes, providing a foundation for investigating how nutrition in ewes influences reproductive performance. This research demonstrates how nutrition regulates reproductive performance by considering the combined perspectives of rumen microbiota and placental function.

UNFERTILIZED EMBRYO SAC 12 phosphorylation plays a crucial role in conferring salt tolerance.

Arabidopsis (Arabidopsis thaliana) UNFERTILIZED EMBRYO SAC 12 (AtUNE12) belongs to the basic helix-loop-helix DNA-binding superfamily of proteins. However, its function is not well known. Here, we found that AtUNE12 plays an important role in mediating salt tolerance. AtUNE12 is a transcriptional activator located in the nucleus whose expression is induced by NaCl, mannitol, and abscisic acid. In addition to binding to the G-box "CACGTG", AtUNE12 also binds to the low temperature responsive element 15 (LTRE15) "CCGAC". Furthermore, the serine residue at position 108 of AtUNE12 is phosphorylated during the salt stress response, enabling AtUNE12 to trigger gene expression by binding to G-box and/or LTRE15 motifs. Phosphorylated AtUNE12 regulates the expression of the genes involved in ion transport leading to reduced Na+ accumulation and K+ loss. At the same time, phosphorylation of AtUNE12 also induces the expression of AtMYB61 to decrease stomatal aperture, leading to a reduced transpiration rate. Overall, AtUNE12 serves as a transcriptional activator that is induced and phosphorylated upon salt stress, and the induction and phosphorylation of AtUNE12 in turn activate the salt-overly-sensitive pathway and decrease the stomatal aperture, enabling improved salt tolerance.

Formation of soil organic carbon pool is regulated by the structure of dissolved organic matter and microbial carbon pump efficacy: A decadal study comparing different carbon management strategies.

To achieve long-term increases in soil organic carbon (SOC) storage, it is essential to understand the effects of carbon management strategies on SOC formation pathways, particularly through changes in microbial necromass carbon (MNC) and dissolved organic carbon (DOC). Using a 14-year field study, we demonstrate that both biochar and maize straw lifted the SOC ceiling, but through different pathways. Biochar, while raising SOC and DOC content, decreased substrate degradability by increasing carbon aromaticity. This resulted in suppressed microbial abundance and enzyme activity, which lowered soil respiration, weakened in vivo turnover and ex vivo modification for MNC production (i.e., low microbial carbon pump "efficacy"), and led to lower efficiency in decomposing MNC, ultimately resulting in the net accumulation of SOC and MNC. In contrast, straw incorporation increased the content and decreased the aromaticity of SOC and DOC. The enhanced SOC degradability and soil nutrient content, such as total nitrogen and total phosphorous, stimulated the microbial population and activity, thereby boosting soil respiration and enhancing microbial carbon pump "efficacy" for MNC production. The total C added to biochar and straw plots were estimated as 27.3-54.5 and 41.4 Mg C ha-1 , respectively. Our results demonstrated that biochar was more efficient in lifting the SOC stock via exogenous stable carbon input and MNC stabilization, although the latter showed low "efficacy". Meanwhile, straw incorporation significantly promoted net MNC accumulation but also stimulated SOC mineralization, resulting in a smaller increase in SOC content (by 50%) compared to biochar (by 53%-102%). The results address the decadal-scale effects of biochar and straw application on the formation of the stable organic carbon pool in soil, and understanding the causal mechanisms can allow field practices to maximize SOC content.

LncRNA-412.25 activates the LIF/STAT3 signaling pathway in ovarian granulosa cells of Hu sheep by sponging miR-346.

Although long non-coding RNAs (lncRNAs) are reported to regulate follicular development and reproductive disease pathogenesis, the underlying mechanisms have not been elucidated. In this study, lncRNA expression profiling of different-sized healthy follicles from Hu sheep with different prolificacy revealed 50 613 lncRNAs. Numerous lncRNAs were differentially expressed among different comparison groups. This study characterized one novel transcript, lncRNA-412.25 (from healthy follicles with a diameter of >5 mm), which was predominantly expressed in the high prolificacy group and localized to the cytoplasm of granulosa cells (GCs). LncRNA-412.25 knockdown promoted and inhibited Hu sheep GC apoptosis and proliferation, respectively. Interestingly, lncRNA-412.25 could directly bind to miR-346, which can target the gene of leukemia inhibitory factor (LIF). Knockdown of lncRNA-412.25 promoted GC apoptosis by downregulating LIF expression, where this effect was attenuated by miR-346. Moreover, the miR-346 inhibitor mitigated the lncRNA-412.25 knockdown-induced downregulation of phosphorylated protein of signal transducer and activator of transcription 3 (STAT3), which was validated using immunofluorescence analysis. Our results demonstrated that lncRNA-412.25 regulates GC proliferation and apoptosis in Hu sheep by binding to miR-346 and then activating the LIF/STAT3 pathway. These findings provide novel insights into the mechanisms underlying prolificacy in sheep.

Apolipoprotein A-1 protected hepatic ischaemia-reperfusion injury through suppressing macrophage pyroptosis via TLR4-NF-κB pathway.

BACKGROUND AND AIMS: Apolipoprotein A-1 (ApoA-1), the major apolipoprotein of high-density lipoprotein, plays anti-atherogenic role in cardiovascular diseases and exerts anti-inflammation effect in various inflammatory and infectious diseases. However, the role and mechanism of ApoA-1 in hepatic ischaemia-reperfusion (I/R) injury is unknown. METHODS: In this study, we measured ApoA-1 expression in human liver grafts after transplantation. Mice partial hepatic I/R injury model was made in ApoA-1 knockout mice, ApoA-1 mimetic peptide D-4F treatment mice and corresponding control mice to examine the effect of ApoA-1 on liver damage, inflammation response and cell death. Primary hepatocytes and macrophages were isolated for in vitro study. RESULTS: The results showed that ApoA-1 expression was down-regulated in human liver grafts after transplantation and mice livers subjected to hepatic I/R injury. ApoA-1 deficiency aggravated liver damage and inflammation response induced by hepatic I/R injury. Interestingly, we found that ApoA-1 deficiency increased pyroptosis instead of apoptosis during acute phase of hepatic I/R injury, which mainly occurred in macrophages rather than hepatocytes. The inhibition of pyroptosis compensated for the adverse impact of ApoA-1 deficiency. Furthermore, the up-regulated pyroptosis process was testified to be mediated by ApoA-1 through TLR4-NF-κB pathway and TLR4 inhibition significantly improved hepatic I/R injury. In addition, we confirmed that D-4F ameliorated hepatic I/R injury. CONCLUSIONS: Our study has identified the protective role of ApoA-1 in hepatic I/R injury through inhibiting pyroptosis in macrophages via TLR4-NF-κB pathway. The effect of ApoA-1 may provide a novel therapeutic approach for hepatic I/R injury.

Comparative genomic analysis of Halomonas campaniensis wild-type and ultraviolet radiation-mutated strains reveal genomic differences associated with increased ectoine production.

Ectoine is a natural amino acid derivative and one of the most widely used compatible solutes produced by Halomonas species that affects both cellular growth and osmotic equilibrium. The positive effects of UV mutagenesis on both biomass and ectoine content production in ectoine-producing strains have yet to be reported. In this study, the wild-type H. campaniensis strain XH26 (CCTCCM2019776) was subjected to UV mutagenesis to increase ectoine production. Eight rounds of mutagenesis were used to generate mutated XH26 strains with different UV-irradiation exposure times. Ectoine extract concentrations were then evaluated among all strains using high-performance liquid chromatography analysis, alongside whole genome sequencing with the PacBio RS II platform and comparison of the wild-type strain XH26 and the mutant strain G8-52 genomes. The mutant strain G8-52 (CCTCCM2019777) exhibited the highest cell growth rate and ectoine yields among mutated strains in comparison with strain XH26. Further, ectoine levels in the aforementioned strain significantly increased to 1.51 ± 0.01 g L-1 (0.65 g g-1 of cell dry weight), representing a twofold increase compared to wild-type cells (0.51 ± 0.01 g L-1) when grown in culture medium for ectoine accumulation. Concomitantly, electron microscopy revealed that mutated strain G8-52 cells were obviously shorter than wild-type strain XH26 cells. Moreover, strain G8-52 produced a relatively stable ectoine yield (1.50 g L-1) after 40 days of continuous subculture. Comparative genomics analysis suggested that strain XH26 harbored 24 mutations, including 10 nucleotide insertions, 10 nucleotide deletions, and unique single nucleotide polymorphisms. Notably, the genes orf00723 and orf02403 (lipA) of the wild-type strain mutated to davT and gabD in strain G8-52 that encoded for 4-aminobutyrate-2-oxoglutarate transaminase and NAD-dependent succinate-semialdehyde dehydrogenase, respectively. Consequently, these genes may be involved in increased ectoine yields. These results suggest that continuous multiple rounds of UV mutation represent a successful strategy for increasing ectoine production, and that the mutant strain G8-52 is suitable for large-scale fermentation applications.

Associations of Life's Simple 7 with cerebral white matter hyperintensities and microstructural integrity: UK Biobank cohort study.

BACKGROUND AND PURPOSE: The American Heart Association Life's Simple 7 (LS7) metric was used to define optimal cardiovascular and brain health, but the associations with macrostructural hyperintensities and microstructural white matter damage are unclear. The objective was to determine the association of LS7 ideal cardiovascular health factors with macrostructural and microstructural integrity. METHOD: A total of 37,140 participants with available LS7 and imaging data from UK Biobank were included in this study. Linear associations were implemented to examine the associations of LS7 score and subscores with white matter hyperintensity load (WMH) (WMH volume normalized by total white matter volume and logit-transformed) and diffusion imaging indices (fractional anisotropy [FA], mean diffusivity, orientation dispersion index [OD], intracellular volume fraction, isotropic volume fraction [ISOVF]). RESULTS: In individuals (mean age 54.76 years; 19,697 females, 52.4%), higher LS7 score and subscores were strongly associated with lower WMH and microstructural white matter injury, including OD, ISOVF, FA. Both interaction analyses and stratified analyses of LS7 score and subscores with age and sex showed a strong association with microstructural damage markers, with remarkable age and sex differences. The association of OD was pronounced in females and populations younger than 50 years and FA, mean diffusivity and ISOVF were pronounced in males and populations older than 50 years. CONCLUSION: These findings suggest that healthier LS7 profiles are associated with better profiles of both macrostructural and microstructural markers of brain health, and indicate that ideal cardiovascular health is associated with improved brain health.

Uncontrolled Two-Step Iterative Calibration Algorithm for Lidar-IMU System.

Calibration of sensors is critical for the precise functioning of lidar-IMU systems. However, the accuracy of the system can be compromised if motion distortion is not considered. This study proposes a novel uncontrolled two-step iterative calibration algorithm that eliminates motion distortion and improves the accuracy of lidar-IMU systems. Initially, the algorithm corrects the distortion of rotational motion by matching the original inter-frame point cloud. Then, the point cloud is further matched with IMU after the prediction of attitude. The algorithm performs iterative motion distortion correction and rotation matrix calculation to obtain high-precision calibration results. In comparison with existing algorithms, the proposed algorithm boasts high accuracy, robustness, and efficiency. This high-precision calibration result can benefit a wide range of acquisition platforms, including handheld, unmanned ground vehicle (UGV), and backpack lidar-IMU systems.

Associations of the A/T/N profiles in PET, CSF, and plasma biomarkers with Alzheimer's disease neuropathology at autopsy.

INTRODUCTION: To examine the extent to which positron emission tomography (PET)-, cerebrospinal fluid (CSF)-, and plasma-related amyloid-ß/tau/neurodegeneration (A/T/N) biomarkers are associated with Alzheimer's disease (AD) neuropathology at autopsy. METHODS: A total of 100 participants who respectively underwent antemortem biomarker measurements and postmortem neuropathology were included in the Alzheimer's Disease Neuroimaging Initiative (ADNI). We examined the associations of PET-, CSF-, and plasma-related A/T/N biomarkers in combinations or alone with AD neuropathological changes (ADNC). RESULTS: PET- and CSF-related A/T/N biomarkers in combination showed high concordance with the ADNC stage and alone showed high accuracy in discriminating autopsy-confirmed AD. However, the plasma-related A/T/N biomarkers alone showed better discriminative performance only when combined with apolipoprotein E (APO)E ε4 genotype. DISCUSSION: This study supports that PET- and CSF-related A/T/N profiles can be used to predict accurately the stages of AD neuropathology. For diagnostic settings, PET-, CSF-, and plasma-related A/T/N biomarkers are all useful diagnostic tools to detect the presence of AD neuropathology. HIGHLIGHTS: PET- and CSF-related A/T/N biomarkers in combination can accurately predict the specific stages of AD neuropathology. PET- and CSF-related A/T/N biomarkers alone may serve as a precise diagnostic tool for detecting AD neuropathology at autopsy. Plasma-related A/T/N biomarkers may need combined risk factors when used as a diagnostic tool. Aß PET and CSF p-tau181/Aß42 were most consistent with Aß pathology, while tau PET and CSF p-tau181/Aß42 were most consistent with tau pathology.