Influences of two transport strategies on AMPK-mediated metabolism and flesh quality of shrimp (Litopenaeus vannamei).

BACKGROUND: Water-free transportation (WFT), as a novel strategy for express delivery of live shrimp (Litopenaeus vannamei), was developed recently. However, air exposure during this transportation arouses a series of abiotic stress to the shrimp. In the present study, the influences of WFT stress on glycolysis and lipolysis metabolism and meat quality (umami flavor and drip loss) were investigated in comparison with conventional water transportation (WT). RESULTS: The results showed that type II muscle fibers with the feature of anaerobic metabolism were dominated in shrimp flesh. In addition, the increments of intracellular Ca2+ was detected in WFT and WT, which then activated the AMP-activated protein kinase pathway and promoted the consumption of glycogen, as well as the accumulation of lactate and lipolysis, under the enzymolysis of hexokinase, pyruvate kinase, lactate dehydrogenase and adipose triglyceride lipase. Glycogen glycolyzed to latate. Meanwhile, ATP degraded along with glycolysis resulting in the generation of ATP-related adenosine phosphates such as inosine monophosphate with umami flavor and phosphoric acid. More remarkable (P < 0.05) physiological changes (except lactate dehydrogenase and lactate) were observed in WFT compared to WT. Additionally, the fatty acid profile also slightly changed. CONCLUSION: The transport stress induced significant energy metabolism changes of shrimp flesh and therefore effected the flesh quality. The intensifications of freshness (K-value) of shrimp flesh were detected as a result of ATP degradation, which were more pronounced after WFT. However, the drip loss of shrimp flesh was more significantly increased (P < 0.05) after WFT compared to WT. © 2023 Society of Chemical Industry.

Conservation Strategies for Aquilaria sinensis: Insights from DNA Barcoding and ISSR Markers.

The evergreen tree species Aquilaria sinensis holds significant economic importance due to its specific medicinal values and increasing market demand. However, the unrestricted illegal exploitation of its wild population poses a threat to its survival. This study aims to contribute to the conservation efforts of A. sinensis by constructing a library database of DNA barcodes, including two chloroplast genes (psbA-trnH and matK) and two nuclear genes (ITS and ITS2). Additionally, the genetic diversity and structure were estimated using inter-simple sequence repeats (ISSR) markers. Four barcodes of 57 collections gained 194 sequences, and 1371 polymorphic bands (98.63%) were observed using DNA ISSR fingerprinting. The Nei's gene diversity (H) of A. sinensis at the species level is 0.2132, while the Shannon information index (I) is 0.3128. The analysis of molecular variance revealed a large significant proportion of total genetic variations and differentiation among populations (Gst = 0.4219), despite a relatively gene flow (Nm = 0.6853) among populations, which were divided into two groups by cluster analysis. There was a close genetic relationship among populations with distances of 0.0845 to 0.5555. This study provides evidence of the efficacy and dependability of establishing a DNA barcode database and using ISSR markers to assess the extent of genetic diversity A. sinensis. Preserving the genetic resources through the conservation of existing populations offers a valuable proposition. The effective utilization of these resources will be further deliberated in subsequent breeding endeavors, with the potential to breed agarwood commercial lines.

Analysis of the chloroplast genome and phylogenetic evolution of Bidens pilosa.

Chloroplast genomes for 3 Bidens plants endemic to China (Bidens bipinnata Linn., Bidens pilosa Linn., and Bidens alba var. radiata) have been sequenced, assembled and annotated in this study to distinguish their molecular characterization and phylogenetic relationships. The chloroplast genomes are in typical quadripartite structure with two inverted repeat regions separating a large single copy region and a small single copy region, and ranged from 151,599 to 154,478 bp in length. Similar number of SSRs and long repeats were found in Bidens, wherein mononucleotide repeats (A/T), forward and palindromic repeats were the most in abundance. Gene loss of clpP and psbD, IR expansion and contraction were detected in these Bidens plants. It seems that ndhE, ndhF, ndhG, and rpl32 from the Bidens plants were under positive selection while the majority of chloroplast genes were under purifying selection. Phylogenetic analysis revealed that 3 Bidens plants clustered together and further formed molophyletic clade with other Bidens species, indicating Bidens plants might be under radiation adaptive selection to the changing environment world-widely. Moreover, mutation hotspot analysis and in silico PCR analysis indicated that inter-genic regions of ndhD-ccsA, ndhI-ndhG, ndhF-rpl32, trnL_UAG-rpl32, ndhE-psaC, matK-rps16, rps2-atpI, cemA-petA, petN-psbM were candidate markers of molecular identification for Bidens plants. This study may provide useful information for genetic diversity analysis and molecular identification for Bidens species.

Genome-wide characterization of regulator of chromosome condensation 1 (RCC1) gene family in Artemisia annua L. revealed a conservation evolutionary pattern.

BACKGROUND: Artemisia annua is the major source for artemisinin production. The artemisinin content in A. annua is affected by different types of light especially the UV light. UVR8, a member of RCC1 gene family was found to be the UV-B receptor in plants. The gene structures, evolutionary history and expression profile of UVR8 or RCC1 genes remain undiscovered in A. annua. RESULTS: Twenty-two RCC1 genes (AaRCC1) were identified in each haplotype genome of two diploid strains of A. annua, LQ-9 and HAN1. Varied gene structures and sequences among paralogs were observed. The divergence of most RCC1 genes occurred at 46.7 - 51 MYA which overlapped with species divergence of core Asteraceae during the Eocene, while no recent novel RCC1 members were found in A. annua genome. The number of RCC1 genes remained stable among eudicots and RCC1 genes underwent purifying selection. The expression profile of AaRCC1 is analogous to that of Arabidopsis thaliana (AtRCC1) when responding to environmental stress. CONCLUSIONS: This study provided a comprehensive characterization of the AaRCC1 gene family and suggested that RCC1 genes were conserved in gene number, structures, constitution of amino acids and expression profiles among eudicots.

Impacts of long-time transportation on whiteleg shrimp (Penaeus vannamei) muscle quality and underlying biochemical mechanisms.

BACKGROUND: Shrimp is widely consumed around the world. Since muscle is the primary edible component of shrimp, muscle quality (particularly texture) has a direct impact on the economic value of shrimp products. However, reports on the shrimp muscle quality influenced by transportation are rather limited, and the underlying mechanism remains unknown. RESULTS: During the simulated transportation, the water pH and total ammonia-nitrogen content and un-ionized ammonia contents were elevated. Furthermore, reductions in shrimp muscle water-holding capacity, hardness, and shear value with intensive myofibrillar protein degradation were detected. Simulated transportation decreased the pH and glycogen content of shrimp muscle while increasing lactic dehydrogenase activity and lactate content, resulting in an elevated level of free calcium ions and increased µ-calpain and general proteolytic activities. Water exchange could improve the water quality and reduce the mortality of shrimp during transportation, as well as decrease muscle textural softening by alleviating these stress responses. CONCLUSIONS: Maintaining water quality and, in particular, reducing ammonia are critical to improving shrimp survival and muscle quality during live transportation. This study is of great significance for the better maintenance of the textural properties of shrimp meat. © 2023 Society of Chemical Industry.

Comparative chloroplast genome analyses of Amomum: insights into evolutionary history and species identification.

BACKGROUND: Species in genus Amomum always have important medicinal and economic values. Classification of Amomum using morphological characters has long been a challenge because they exhibit high similarity. The main goals of this study were to mine genetic markers from cp genomes for Amomum species identification and discover their evolutionary history through comparative analysis. RESULTS: Three species Amomum villosum, Amomum maximum and Amomum longipetiolatum were sequenced and annotated for the complete chloroplast (cp) genomes, and the cp genomes of A. longipetiolatum and A. maximum were the first reported. Three cp genomes exhibited typical quadripartite structures with 163,269-163,591 bp in length. Each genome encodes 130 functional genes including 79 protein-coding, 26 tRNAs and 3 rRNAs genes. 113-152 SSRs and 99 long repeats were identified in the three cp genomes. By designing specific primers, we amplified the highly variable loci and the mined genetic marker ccsA exhibited a relatively high species identification resolution in Amomum. The nonsynonymous and synonymous substitution ratios (Ka/Ks) in Amomum and Alpinia showed that most genes were subjected to a purifying selection. Phylogenetic analysis revealed the evolutionary relationships of Amomum and Alpinia species and proved that Amomum is paraphyletic. In addition, the sequenced sample of A. villosum was found to be a hybrid, becoming the first report of natural hybridization of this genus. Meanwhile, the high-throughput sequencing-based ITS2 analysis was proved to be an efficient tool for interspecific hybrid identification and with the help of the chloroplast genome, the hybrid parents can be also be determined. CONCLUSION: The comparative analysis and mined genetic markers of cp genomes were conducive to species identification and evolutionary relationships of Amomum.

MoS2 decorated nanocomposite: Fe2O3@MoS2 inhibits the conjugative transfer of antibiotic resistance genes.

Nanomaterials of Al2O3 and TiO2 have been proved to promote the spread of antibiotic resistance genes (ARGs) by horizontal gene transfer. In this work, we found that Fe2O3@MoS2 nanocomposite inhibited the horizontal gene transfer (HGT) by inhibiting the conjugative transfer mediated by RP4-7 plasmid. To discover the mechanism of Fe2O3@MoS2 inhibiting HGT, the bacterial cells were collected under the optimal mating conditions. The collected bacterial cells were used for analyzing the expression levels of genes unique to the plasmid and the bacterial chromosome in the conjugation system by qPCR. The results of genes expression demonstrated that the mechanism of Fe2O3@MoS2 inhibited conjugation by promoting the expression of global regulatory gene (trbA) and inhibiting the expression of conjugative transfer genes involved in mating pair formation (traF, trbB) and DNA replication (trfA). The risk assessment of Fe2O3@MoS2 showed that it had very low toxicity to organisms. The findings of this paper showed that Fe2O3@MoS2, as an inhibitor of horizontal gene transfer, is an environment-friendly material.

Key Role of TFEB Nucleus Translocation for Silver Nanoparticle-Induced Cytoprotective Autophagy.

Transcription factor EB (TFEB) is a master regulator of autophagy and lysosomal biogenesis. Here, silver nanoparticles (Ag NPs)-induced cytoprotective autophagy required TFEB is shown. Ag NPs-induced nucleus translocation of TFEB through a well-established mechanism involving dephosphorylation of TFEB at serine-142 and serine-211 but independent of both the mTORC1 and ERK1/2 pathways. TFEB nucleus translocation precedes autophagy induced by Ag NPs and leads to enhanced expression of autophagy-essential genes. Knocking down the expression of TFEB attenuates the autophagy induction is demonstrated, and in the meantime, enhanced cell killing in HeLa cells treats with Ag NPs, indicating that TFEB is the key mediator for Ag NPs-induced cytoprotective autophagy. The results pinpoint TFEB as a potential target for developing more effective Ag NPs-based cancer therapeutics.

Genome-Wide Identification and Comparative Analysis for OPT Family Genes in Panax ginseng and Eleven Flowering Plants.

Herb genomics and comparative genomics provide a global platform to explore the genetics and biology of herbs at the genome level. Panax ginseng C.A. Meyer is an important medicinal plant for a variety of bioactive chemical compounds of which the biosynthesis may involve transport of a wide range of substrates mediated by oligopeptide transporters (OPT). However, information about the OPT family in the plant kingdom is still limited. Only 17 and 18 OPT genes have been characterized for Oryza sativa and Arabidopsis thaliana, respectively. Additionally, few comprehensive studies incorporating the phylogeny, gene structure, paralogs evolution, expression profiling, and co-expression network between transcription factors and OPT genes have been reported for ginseng and other species. In the present study, we performed those analyses comprehensively with both online tools and standalone tools. As a result, we identified a total of 268 non-redundant OPT genes from 12 flowering plants of which 37 were from ginseng. These OPT genes were clustered into two distinct clades in which clade-specific motif compositions were considerably conservative. The distribution of OPT paralogs was indicative of segmental duplication and subsequent structural variation. Expression patterns based on two sources of RNA-Sequence datasets suggested that some OPT genes were expressed in both an organ-specific and tissue-specific manner and might be involved in the functional development of plants. Further co-expression analysis of OPT genes and transcription factors indicated 141 positive and 11 negative links, which shows potent regulators for OPT genes. Overall, the data obtained from our study contribute to a better understanding of the complexity of the OPT gene family in ginseng and other flowering plants. This genetic resource will help improve the interpretation on mechanisms of metabolism transportation and signal transduction during plant development for Panax ginseng.

Comprehensive Characterization for Ginsenosides Biosynthesis in Ginseng Root by Integration Analysis of Chemical and Transcriptome.

Herbgenomics provides a global platform to explore the genetics and biology of herbs on the genome level. Panax ginseng C.A. Meyer is an important medicinal plant with numerous pharmaceutical effects. Previous reports mainly discussed the transcriptome of ginseng at the organ level. However, based on mass spectrometry imaging analyses, the ginsenosides varied among different tissues. In this work, ginseng root was separated into three tissues-periderm, cortex and stele-each for five duplicates. The chemical analysis and transcriptome analysis were conducted simultaneously. Gene-encoding enzymes involved in ginsenosides biosynthesis and modification were studied based on gene and molecule data. Eight widely-used ginsenosides were distributed unevenly in ginseng roots. A total of 182,881 unigenes were assembled with an N50 contig size of 1374 bp. About 21,000 of these unigenes were positively correlated with the content of ginsenosides. Additionally, we identified 192 transcripts encoding enzymes involved in two triterpenoid biosynthesis pathways and 290 transcripts encoding UDP-glycosyltransferases (UGTs). Of these UGTs, 195 UGTs (67.2%) were more highly expressed in the periderm, and that seven UGTs and one UGT were specifically expressed in the periderm and stele, respectively. This genetic resource will help to improve the interpretation on complex mechanisms of ginsenosides biosynthesis, accumulation, and transportation.

Rapid separation and characterization of diterpenoid alkaloids in processed roots of Aconitum carmichaeli using ultra high performance liquid chromatography coupled with hybrid linear ion trap-Orbitrap tandem mass spectrometry.

The lateral root of Aconitum carmichaeli, a popular traditional Chinese medicine, has been widely used to treat rheumatic diseases. For decades, diterpenoid alkaloids have dominated the phytochemical and biomedical research on this plant. In this study, a rapid and sensitive method based on ultra high performance liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry was developed to characterize the diterpenoid alkaloids in Aconitum carmichaeli. Based on an optimized chromatographic condition, more than 120 diterpenoid alkaloids were separated with good resolution. Using a systematic strategy that combines high resolution separation, highly accurate mass measurements and a good understanding of the diagnostic fragment-based fragmentation patterns, these diterpenoid alkaloids were identified or tentatively identified. The identification of these chemicals provided essential data for further phytochemical studies and toxicity research of Aconitum carmichaeli. Moreover, the ultra high performance liquid chromatography with linear ion trap-Orbitrap mass spectrometry platform was an effective and accurate tool for rapid qualitative analysis of secondary metabolite productions from natural resources.

Myelin Pathology in Alzheimer's Disease: Potential Therapeutic Opportunities.

Alzheimer's disease (AD) is an age-related neurodegenerative disease characterized by memory loss and cognitive decline. Despite significant efforts over several decades, our understanding of the pathophysiology of this disease is still incomplete. Myelin is a multi-layered membrane structure ensheathing neuronal axons, which is essential for the fast and effective propagation of action potentials along the axons. Recent studies highlight the critical involvement of myelin in memory consolidation and reveal its vulnerability in various pathological conditions. Notably, apart from the classic amyloid hypothesis, myelin degeneration has been proposed as another critical pathophysiological feature of AD, which could occur prior to the development of amyloid pathology. Here, we review recent works supporting the critical role of myelin in cognition and myelin pathology during AD progression, with a focus on the mechanisms underlying myelin degeneration in AD. We also discuss the complex intersections between myelin pathology and typical AD pathophysiology, as well as the therapeutic potential of pro-myelinating approaches for this disease. Overall, these findings implicate myelin degeneration as a critical contributor to AD-related cognitive deficits and support targeting myelin repair as a promising therapeutic strategy for AD.

Photobiomodulation in experimental models of Alzheimer's disease: state-of-the-art and translational perspectives.

Alzheimer's disease (AD) poses a significant public health problem, affecting millions of people across the world. Despite decades of research into therapeutic strategies for AD, effective prevention or treatment for this devastating disorder remains elusive. In this review, we discuss the potential of photobiomodulation (PBM) for preventing and alleviating AD-associated pathologies, with a focus on the biological mechanisms underlying this therapy. Future research directions and guidance for clinical practice for this non-invasive and non-pharmacological therapy are also highlighted. The available evidence indicates that different treatment paradigms, including transcranial and systemic PBM, along with the recently proposed remote PBM, all could be promising for AD. PBM exerts diverse biological effects, such as enhancing mitochondrial function, mitigating the neuroinflammation caused by activated glial cells, increasing cerebral perfusion, improving glymphatic drainage, regulating the gut microbiome, boosting myokine production, and modulating the immune system. We suggest that PBM may serve as a powerful therapeutic intervention for AD.

Enhancing axonal myelination: Clemastine attenuates cognitive impairment in a rat model of diffuse traumatic brain injury.

Traumatic brain injury (TBI) has a significant impact on cognitive function, affecting millions of people worldwide. Myelin loss is a prominent pathological feature of TBI, while well-functioning myelin is crucial for memory and cognition. Utilizing drug repurposing to identify effective drug candidates for TBI treatment has gained attention. Notably, recent research has highlighted the potential of clemastine, an FDA-approved allergy medication, as a promising pro-myelinating drug. Therefore, in this study, we aim to investigate whether clemastine can enhance myelination and alleviate cognitive impairment following mild TBI using a clinically relevant rat model of TBI. Mild diffuse TBI was induced using the Closed-Head Impact Model of Engineered Rotational Acceleration (CHIMERA). Animals were treated with either clemastine or an equivalent volume of the vehicle from day 1 to day 14 post-injury. Following treatment, memory-related behavioral tests were conducted, and myelin pathology in the cortex and hippocampus was assessed through immunofluorescence staining and ProteinSimple® capillary-based immunoassay. Our results showed that TBI leads to significant myelin loss, axonal damage, glial activation, and a decrease in mature oligodendrocytes in both the cortex and hippocampus. The TBI animals also exhibited notable deficits in memory-related tests. In contrast, animals treated with clemastine showed an increase in mature oligodendrocytes, enhanced myelination, and improved performance in the behavioral tests. These preliminary findings support the therapeutic value of clemastine in alleviating TBI-induced cognitive impairment, with substantial clinical translational potential. Our findings also underscore the potential of remyelinating therapies for TBI.

Intermittent theta-burst stimulation alleviates hypoxia-ischemia-caused myelin damage and neurologic disability.

Neonatal hypoxia-ischemia (HI) results in behavioral deficits, characterized by neuronal injury and retarded myelin formation. To date, limited treatment methods are available to prevent or alleviate neurologic sequelae of HI. Intermittent theta-burst stimulation (iTBS), a non-invasive therapeutic procedure, is considered a promising therapeutic tool for treating some neurocognitive disorders and neuropsychiatric diseases. Hence, this study aims to investigate whether iTBS can prevent the negative behavioral manifestations of HI and explore the mechanisms for associations. We exposed postnatal day 10 Sprague-Dawley male and female rats to 2 h of hypoxia (6% O2) following right common carotid artery ligation, resulting in oligodendrocyte (OL) dysfunction, including reduced proliferation and differentiation of oligodendrocyte precursor cells (OPCs), decreased OL survival, and compromised myelin in the corpus callosum (CC) and hippocampal dentate gyrus (DG). These alterations were concomitant with cognitive dysfunction and depression-like behaviors. Crucially, early iTBS treatment (15 G, 190 s, seven days, initiated one day post-HI) significantly alleviated HI-caused myelin damage and mitigated the neurologic sequelae both in male and female rats. However, the late iTBS treatment (initiated 18 days after HI insult) could not significantly impact these behavioral deficits. In summary, our findings support that early iTBS treatment may be a promising strategy to improve HI-induced neurologic disability. The underlying mechanisms of iTBS treatment are associated with promoting the differentiation of OPCs and alleviating myelin damage.

Processing of Reynoutria multiflora: transformation of catechin and gallic acid derivatives and their identification.

Introduction: The root of Reynoutria multiflora (Thunb.) Moldenke (RM) has been used widely in formulations of herbal medicines in China for centuries. Raw R. multiflora (RRM) should be processed before use to reduce toxicity and increase efficacy. However, detailed regulation of the processing endpoint is lacking, and the duration of processing can vary considerably. We conducted in-depth research on stilbene glycosides in RM at different processing times. Previously, we discovered that 219 stilbene glycosides changed markedly in quantity and content. Therefore, we proposed that processing causes changes in various chemical groups. Methods: To better explain the mechanism of RM processing for toxicity reduction and efficacy enhancement, we used a method of tandem mass spectrometry described previously to research gallic acid based and catechin based metabolites. Results: A total of 259 metabolites based on gallic acid and 112 metabolites based on catechins were identified. Among these, the peak areas of 157 gallic acid and 81 catechins gradually decreased, those of another 71 gallic acid and 30 catechins first increased and then decreased, those of 14 gallic acid and 1 catechin gradually increased. However, 17 of the gallic acids showed no significant changes. We speculate that many gallic acid metabolites hydrolyze to produce gallic acid; moreover, the dimers/trimers of catechins, after being cleaved into catechins, epicatechin, gallic acid catechins, and epicatechin monomers, are cleaved into gallic acid and protocatechualdehyde under high temperature and high humidity, subsequently participating in the Maillard reaction and browning reactions. Discussion: We showed that processing led to changes in chemical groups, clarification of the groups of secondary metabolites could provide a basis for research on the pharmacological and toxic mechanisms of RM, as well as the screening of related markers.

Photobiomodulation Inhibits Ischemia-Induced Brain Endothelial Senescence via Endothelial Nitric Oxide Synthase.

Recent research suggests that photobiomodulation therapy (PBMT) positively impacts the vascular function associated with various cerebrovascular diseases. Nevertheless, the specific mechanisms by which PBMT improves vascular function remain ambiguous. Since endothelial nitric oxide synthase (eNOS) is crucial in regulating vascular function following cerebral ischemia, we investigated whether eNOS is a key element controlling cerebrovascular function and the senescence of vascular endothelial cells following PBMT treatment. Both rat photothrombotic (PT) stroke and in vitro oxygen-glucose deprivation (OGD)-induced vascular endothelial injury models were utilized. We demonstrated that treatment with PBMT (808 nm, 350 mW/cm2, 2 min/day) for 7 days significantly reduced PT-stroke-induced vascular permeability. Additionally, PBMT inhibited the levels of endothelial senescence markers (senescence green and p21) and antiangiogenic factor (endostatin), while increasing the phospho-eNOS (Ser1177) in the peri-infarct region following PT stroke. In vitro study further indicated that OGD increased p21, endostatin, and DNA damage (γH2AX) levels in the brain endothelial cell line, but they were reversed by PBMT. Intriguingly, the beneficial effects of PBMT were attenuated by a NOS inhibitor. In summary, these findings provide novel insights into the role of eNOS in PBMT-mediated protection against cerebrovascular senescence and endothelial dysfunction following ischemia. The use of PBMT as a therapeutic is a promising strategy to improve endothelial function in cerebrovascular disease.

Mineralization, degradation and osteogenic property of polylactide multicomponent porous composites for bone repair: In vitro and in vivo study.

Gelatin and hydroxyapatite were assembled into polylactide porous matrix to prepare multicomponent porous composites for bone repair (PLA-gH). PLA-gH possessed a superior ability of mineralization. During simulated body fluids (SBF), the spherical Ca-P depositions on surface of PLA-gH became bulk as Ca/P decreased, while they locally turned into the rod with different variation in Ca/P during SBF containing bovine serum albumin (SBF-BSA), indicating that the mineralization of PLA-gH could be regulated by BSA. Meanwhile, PLA-gH possessed good degradation behaviour, especially in SBF-BSA, the degradation of PLA porous matrix was higher than that in SBF after 14-day immersion, whose crystallinity (Xc) decreased to a slightly lower level. Gelatin and hydroxyapatite endowed PLA-gH with good osteogenic property, characterized by obvious osteogenic differentiation and bone regeneration. In terms of predicting the cytocompatibility, osteogenic differentiation and new bone mineralization of PLA-gH by in vitro methods, applying SBF-BSA may be more reliable than SBF.

Construction and validation of risk prediction models for pulmonary embolism in hospitalized patients based on different machine learning methods.

Objective: This study aims to apply different machine learning (ML) methods to construct risk prediction models for pulmonary embolism (PE) in hospitalized patients, and to evaluate and compare the predictive efficacy and clinical benefit of each model. Methods: We conducted a retrospective study involving 332 participants (172 PE positive cases and 160 PE negative cases) recruited from Guangdong Medical University. Participants were randomly divided into a training group (70%) and a validation group (30%). Baseline data were analyzed using univariate analysis, and potential independent risk factors associated with PE were further identified through univariate and multivariate logistic regression analysis. Six ML models, namely Logistic Regression (LR), Decision Tree (DT), Random Forest (RF), Naive Bayes (NB), Support Vector Machine (SVM), and AdaBoost were developed. The predictive efficacy of each model was compared using the receiver operating characteristic (ROC) curve analysis and the area under the curve (AUC). Clinical benefit was assessed using decision curve analysis (DCA). Results: Logistic regression analysis identified lower extremity deep venous thrombosis, elevated D-dimer, shortened activated partial prothrombin time, and increased red blood cell distribution width as potential independent risk factors for PE. Among the six ML models, the RF model achieved the highest AUC of 0.778. Additionally, DCA consistently indicated that the RF model offered the greatest clinical benefit. Conclusion: This study developed six ML models, with the RF model exhibiting the highest predictive efficacy and clinical benefit in the identification and prediction of PE occurrence in hospitalized patients.

Activation of testosterone-androgen receptor mediates cerebrovascular protection by photobiomodulation treatment in photothrombosis-induced stroke rats.

RATIONALE: Numerous epidemiological studies have reported a link between low testosterone levels and an increased risk of cerebrovascular disease in men. However, there is ongoing controversy surrounding testosterone replacement therapy due to potential side effects. PBMT has been demonstrated to improve cerebrovascular function and promote testosterone synthesis in peripheral tissues. Despite this, the molecular mechanisms that could connect PBMT with testosterone and vascular function in the brain of photothrombosis (PT)-induced stroke rats remain largely unknown. METHODS: We measured behavioral performance, cerebral blood flow (CBF), vascular permeability, and the expression of vascular-associated and apoptotic proteins in PT-induced stroke rats treated with flutamide and seven consecutive days of PBM treatment (350 mW, 808 nM, 2 min/day). To gain further insights into the mechanism of PBM on testosterone synthesis, we used testosterone synthesis inhibitors to study their effects on bEND.3 cells. RESULTS: We showed that PT stroke caused a decrease in cerebrovascular testosterone concentration, which was significantly increased by 7-day PBMT (808 nm, 350 mW/cm2 , 42 J/cm2 ). Furthermore, PBMT significantly increased cerebral blood flow (CBF) and the expression of vascular-associated proteins, while inhibiting vascular permeability and reducing endothelial cell apoptosis. This ultimately mitigated behavioral deficits in PT stroke rats. Notably, treatment with the androgen receptor antagonist flutamide reversed the beneficial effects of PBMT. Cellular experiments confirmed that PBMT inhibited cell apoptosis and increased vascular-associated protein expression in brain endothelial cell line (bEnd.3) subjected to oxygen-glucose deprivation (OGD). However, these effects were inhibited by flutamide. Moreover, mechanistic studies revealed that PBMT-induced testosterone synthesis in bEnd.3 cells was partly mediated by 17ß-hydroxysteroid dehydrogenase 5 (17ß-HSD5). CONCLUSIONS: Our study provides evidence that PBMT attenuates cerebrovascular injury and behavioral deficits associated with testosterone/AR following ischemic stroke. Our findings suggest that PBMT may be a promising alternative approach for managing cerebrovascular diseases.