Nobiletin Protects Against Alcoholic Liver Disease in Mice via the BMAL1-AKT-Lipogenesis Pathway.

SCOPE: Alcoholic liver disease (ALD) is a global public health concern. Nobiletin, a polymethoxyflavone abundant in citrus fruits, enhances circadian rhythms and ameliorates diet-induced hepatic steatosis, but its influences on ALD are unknown. This study investigates the role of brain and muscle Arnt-like protein-1 (Bmal1), a key regulator of the circadian clock, in nobiletin-alleviated ALD. METHODS AND RESULTS: This study uses chronic ethanol feeding plus an ethanol binge to establish ALD models in Bmal1flox/flox and Bmal1 liver-specific knockout (Bmal1LKO) mice. Nobiletin mitigates ethanol-induced liver injury (alanine aminotransferase [ALT]), glucose intolerance, hepatic apoptosis, and lipid deposition (triglyceride [TG], total cholesterol [TC]) in Bmal1flox/flox mice. Nobiletin fails to modulated liver injury (ALT, aspartate aminotransferase [AST]), apoptosis, and TG accumulation in Bmal1LKO mice. The expression of lipogenic genes (acetyl-CoA carboxylase alpha [Acaca], fatty acid synthase [Fasn]) and fatty acid oxidative genes (carnitine pamitoyltransferase [Cpt1a], cytochrome P450, family 4, subfamily a, polypeptide 10 [Cyp4a10], and cytochrome P450, family4, subfamily a, polypeptide 14 [Cyp4a14]) is inhibited, and the expression of proapoptotic genes (Bcl2 inteacting mediator of cell death [Bim]) is enhanced by ethanol in Bmal1flox/flox mice. Nobiletin antagonizes the expression of these genes in Bmal1flox/flox mice and not in Bmal1LKO mice. Nobiletin activates protein kinase B (PKB, also known as AKT) phosphorylation, increases the levels of the carbohydrate response element binding protein (ChREBP), ACC1, and FASN, and reduces the level of sterol-regulatory element binding protein 1 (SREBP1) and phosphorylation of ACC1 in a Bmal1-dependent manner. CONCLUSION: Nobiletin alleviates ALD by increasing the expression of genes involved in fatty acid oxidation by increasing AKT phosphorylation and lipogenesis in a Bmal1-dependent manner.

Characteristics of symptoms and development of psychological status in late Chinese adolescence.

BACKGROUND: Many late adolescents experience a state of psychological sub-health, requiring early recognition and intervention. This study aims to assess the psychological state of late Chinese adolescents and uncover developmental trend of mental health through network analysis. METHOD: We analyzed data from, 9072 Chinese high school adolescents in Shandong Province surveyed in 2020-2021, dividing them into normal, suspected, and abnormal groups based on Symptom Checklist 90 (SCL-90) scores. Network analysis was employed to identify the core symptoms and bridge symptoms across different states. RESULTS: Anxiety and depression were the most central symptoms, without gender differences. Core symptoms, network structure and network invulnerability varied across different psychological states. Abnormal groups exhibited the highest value of natural connectivity, followed by the suspected and the normal groups. This pattern extended to bridge networks. While not meeting diagnostic criteria, the suspected group demonstrated abnormalities in network edge invariance and global strength invariance. LIMITATIONS: The cross-sectional design cannot establish causality, and biases in self-report measurements cannot be ignored. CONCLUSION: Compared to traditional scale indicators, network structural characteristics may be a more sensitive assessment indicator.

Anti-influenza activity of CPAVM1 protease secreted by Bacillus subtilis LjM2.

Bacillus spp. has been considered a promising source for identifying new antimicrobial substances, including anti-viral candidates. Here, we successfully isolated a number of bacteria strains from aged dry citrus peel (Chenpi). Of note, the culture supernatant of a new isolate named Bacillus subtilis LjM2 demonstrated strong inhibition of influenza A virus (IAV) infection in multiple experimental systems in vitro and in vivo. In addition, the anti-viral effect of LjM2 was attributed to its direct lysis of viral particles. Further analysis showed that a protease which we named CPAVM1 isolated from the culture supernatant of LjM2 was the key component responsible for its anti-viral function. Importantly, the therapeutic effect of CPAVM1 was still significant when applied 12 hours after IAV infection of experimental mice. Moreover, we found that the CPAVM1 protease cleaved multiple IAV proteins via targeting basic amino acid Arg or Lys. Furthermore, this study reveals the molecular structure and catalytic mechanism of CPAVM1 protease. During catalysis, Tyr75, Tyr77, and Tyr102 are important active sites. Therefore, the present work identified a special protease CPAVM1 secreted by a new strain of Bacillus subtilis LjM2 against influenza A virus infection via direct cleavage of critical viral proteins, thus facilitates future biotechnological applications of Bacillus subtilis LjM2 and the protease CPAVM1.

Compendium of 5810 genomes of sheep and goat gut microbiomes provides new insights into the glycan and mucin utilization.

BACKGROUND: Ruminant gut microbiota are critical in ecological adaptation, evolution, and nutrition utilization because it regulates energy metabolism, promotes nutrient absorption, and improves immune function. To study the functional roles of key gut microbiota in sheep and goats, it is essential to construct reference microbial gene catalogs and high-quality microbial genomes database. RESULTS: A total of 320 fecal samples were collected from 21 different sheep and goat breeds, originating from 32 distinct farms. Metagenomic deep sequencing and binning assembly were utilized to construct a comprehensive microbial genome information database for the gut microbiota. We successfully generated the largest reference gene catalogs for gut microbiota in sheep and goats, containing over 162 million and 82 million nonredundant predicted genes, respectively, with 49 million shared nonredundant predicted genes and 1138 shared species. We found that the rearing environment has a greater impact on microbial composition and function than the host's species effect. Through subsequent assembly, we obtained 5810 medium- and high-quality metagenome-assembled genomes (MAGs), out of which 2661 were yet unidentified species. Among these MAGs, we identified 91 bacterial taxa that specifically colonize the sheep gut, which encode polysaccharide utilization loci for glycan and mucin degradation. CONCLUSIONS: By shedding light on the co-symbiotic microbial communities in the gut of small ruminants, our study significantly enhances the understanding of their nutrient degradation and disease susceptibility. Our findings emphasize the vast potential of untapped resources in functional bacterial species within ruminants, further expanding our knowledge of how the ruminant gut microbiota recognizes and processes glycan and mucins. Video Abstract.

Endovaginal coil for pelvic high-resolution magnetic resonance imaging of cervical cancer: a preliminary parameter optimization study.

Background: The diagnosis of early-stage cervical cancer through conventional magnetic resonance imaging (MRI) remains challenging, highlighting a greater need for pelvic high-resolution MRI (HR MRI). This study used our research team's endovaginal coil imaging to optimize scanning parameters and aimed to achieve HR MRI of the pelvis and determine its clinical value. Methods: Fifty participants were recruited prospectively for this cross-sectional study conducted at the First Affiliated Hospital of Chongqing Medical University from January 2023 to November 2023. Initially, 10 volunteers requiring pelvic imaging diagnosis underwent pelvic MRI with the endovaginal coil combined with a conventional external array coil to test and optimize the scanning parameters. Subsequently, 40 patients who were highly suspected or diagnosed with cervical cancer were randomly assigned to undergo an initial pelvic scan with an external array coil with subsequent examinations of both the conventional coil and the endovaginal coil. Two experienced radiologists performed quantitative analyses, measuring signals and calculating the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and contrast (C). They also conducted qualitative analyses, evaluating imaging artifacts, anatomical structures, and overall image quality. The paired sample t-test and Wilcoxon rank-sum test were conducted to compare the statistical differences between the two sets of images, while the intraclass correlation coefficient (ICC) and Kappa consistency tests were used to assess the measurement and scoring consistency between the two radiologists. Results: The optimized endovaginal images had higher mean SNR, CNR, and C values (18.62±7.85, 16.04±7.72, and 0.73±0.11, respectively) compared to the conventional images (6.77±2.36, 4.47±2.05, and 0.47±0.12, respectively). Additionally, the ratings for imaging artifacts, anatomical structures, and overall quality of the endovaginal images were all 4 [interquartile range (IQR) 4, 4]; meanwhile, the conventional images scored lower with ratings of 4 (IQR 3, 4), 3 (IQR 3, 3), and 3 (IQR 3, 3) for SNR, CNR, and C, respectively. All analysis results underwent paired-sample t-tests or Wilcoxon rank-sum tests between the two groups, yielding a P value <0.001. The optimized endovaginal images also showed improved resolution with a reconstructed voxel size of 0.11 mm3, and HR MRI was successfully achieved. The ICC values for the measurements were 0.914, 0.947, and 0.912, respectively, and for the ratings, the measurement was 0.923, indicating excellent consistency between the two physicians (ICC/Kappa value between 0.85 and 1.00). Conclusions: Endovaginal technology, which provides precise clinical information for the diagnosis of cervical cancer, provides straightforward operation and exceptional imaging quality, making it highly suitable for expanded clinical use.

Genome-wide analysis reveals genomic diversity and signatures of selection in Qinchuan beef cattle.

BACKGROUND: Indigenous Chinese cattle have abundant genetic diversity and a long history of artificial selection, giving local breeds advantages in adaptability, forage tolerance and resistance. The detection of selective sweeps and comparative genome analysis of selected breeds and ancestral populations provide a basis for understanding differences among breeds and for the identification and utilization of candidate genes. We investigated genetic diversity, population structure, and signatures of selection using genome-wide sequencing data for a new breed of Qinchuan cattle (QNC, n = 21), ancestral Qinchuan cattle (QCC, n = 20), and Zaosheng cattle (ZSC, n = 19). RESULTS: A population structure analysis showed that the ancestry components of QNC and ZSC were similar. In addition, the QNC and ZSC groups showed higher proportions of European taurine ancestry than that of QCC, and this may explain the larger body size of QNC, approaching that of European cattle under long-term domestication and selection. A neighbor-joining tree revealed that QCC individuals were closely related, whereas QNC formed a distinct group. To search for signatures of selection in the QNC genome, we evaluated nucleotide diversity (θπ), the fixation index (FST) and Tajima's D. Overlapping selective sweeps were enriched for one KEGG pathway, the apelin signaling pathway, and included five candidate genes (MEF2A, SMAD2, CAMK4, RPS6, and PIK3CG). We performed a comprehensive review of genomic variants in QNC, QCC, and ZSC using whole-genome sequencing data. QCC was rich in novel genetic diversity, while diversity in QNC and ZSC cattle was reduced due to strong artificial selection, with divergence from the original cattle. CONCLUSIONS: We identified candidate genes associated with production traits. These results support the success of selective breeding and can guide further breeding and resource conservation of Qinchuan cattle.

The spectrum of factor XI deficiency in Southeast China: four recurrent variants can explain most of the deficiencies.

BACKGROUND: Factor XI (FXI) deficiency is an autosomal hemorrhagic disorder characterized by reduced plasma FXI levels. Multiple ancestral variants in the F11 gene have been identified in Ashkenazi Jews and other selected European populations. However, there are few reports of predominant variants in Chinese and/or East Asian populations. The aim of this study is to characterize the genotypes and phenotypes of FXI deficiency and identify the predominant variants. RESULTS: Of the 41 FXI-deficient patients, 39 exhibited severe FXI defects, considerably more than those with partial defects. The APTT levels showed a negative correlation with FXI activity levels (coefficient=-0.584, P < .001). Only nine patients experienced mild bleeding, including one partially defective patient and eight severely defective patients. The majority of patients were referred for preoperative screenings (n = 22) and checkups (n = 14). Genetic analysis revealed that 90% of the patients had genetic defects, with 2, 16, and 19 cases of heterozygous, homozygous, and compound heterozygous patients, respectively. Seventeen variants were detected in the F11 gene (6 novel), including eleven missense variants, four nonsense variants, and two small deletions scattered throughout the F11. Of the 11 missense variants, six have not yet been studied for in vitro expression. Protein modeling analyses indicated that all of these variants disrupted local structural stability by altering side-chain orientation and hydrogen bonds. Nine variants, consisting of three missense and six null variants, were detected with a frequency of two or more. The highest allele frequency was observed in p.Q281* (21.25%), p.W246* (17.50%), p.Y369* (12.50%), and p.L442Cfs*8 (12.50%). The former two were variants specific to East Asia, while the remaining two were southeast China-specific variants. CONCLUSION: Our population-based cohort demonstrated that no correlation between the level of FXI activity and the bleeding severity in FXI deficiency. Additionally, the prevalence of FXI deficiency may have been underestimated. The nonsense p.Q281* was the most common variant in southeast China, suggesting a possible founder effect.

Analysis of the Efficacy of Neuroendoscopic Hematoma Removal Combined With Ventricular Lavage in Severe Intraventricular Hemorrhage-A Prospective Randomized Controlled Study.

BACKGROUND AND OBJECTIVES: The current widely utilized clinical approach for severe intraventricular hemorrhage involves ventriculostomy with supportive drainage. The aim of our study was to evaluate the overall efficacy of neuroendoscopic hematoma removal combined with ventricular lavage as a treatment approach for severe intraventricular hemorrhage. METHODS: A prospective randomized controlled study was conducted, selecting a total of 98 patients with severe intraventricular hemorrhage at our hospital from February 2021 to November 2022. The patients were randomly distributed into 2 groups using a randomized number table method: the neuroendoscopic group (undergoing neuroendoscopic hematoma removal combined with ventricular lavage) and the control group (undergoing intraventricular trepanation and drainage), with 49 patients in each group. RESULTS: The neuroendoscopic group had significantly higher intraoperative blood loss than that of the control group (P = .037), while the drainage tube indwelling time and hospital stay in the neuroendoscopic group were significantly shorter (P < .001). At 6 hours (P = .021), 1 day (P = .002), 3 days (P < .001) and 7 days (P = .007) following surgery, the neuroendoscopic group exhibited evidently higher hematoma clearance rates compared with the control group. At 1 day and 3 days after surgery, the cerebrospinal fluid drainage volume in the neuroendoscopic group was significantly higher than that in the control group (P < .001), whereas at 7 days after surgery, it was significantly lower in the neuroendoscopic group compared with the control group (P < .001). Moreover, significantly lower incidence of intracranial infection (P = .045) and increased intracranial pressure (P = .008) was observed in the neuroendoscopic group compared with the control group. CONCLUSION: Neuroendoscopic hematoma removal combined with ventricle lavage emerged as an effective treatment strategy for severe intraventricular hemorrhage, yielding significant therapeutic benefits. Therefore, this approach holds promise for broader clinical application and promotion.

Development of an active biogenic silver nanoparticles composite film based on berry wax and chitosan for rabbit meat preservation.

This study aimed to develop an eco-friendly active biogenic nanocomposite film through the complexation of silver nanoparticles (AgNPs), berry wax (BYW), and chitosan (CT) for maintiaing rabbit functional meat freshness. AgNPs were synthesized using Chinese medicinal paeoniaceae petal extract, and they were loaded at various concentrations (0.5 %, 0.75 %, 1.0 %, 1.25 %, and 1.5 % based on CT w/w) into the CT/BYW complex. The AgNPs exhibited an average size of 55 nm and a zeta potential of -26.3 mV with a spherical shape. The particle size and zeta potential of the film dispersions were 370.5-529.5 nm and 40.17-49.345 mV, respectively. FTIR, SEM, and XRD results showed compatibility among AgNPs and CT/BYW structure. The film water vapor permeability and light transparency decreased from 6.5 to 3.5 and 10 to 0.78 %, respectively, while opacity increased from 1.76 to 9.96 % with increasing concentrations of AgNPs. Among them, the film composite CT/BYW/AgNPs1.5% had better antioxidant and antibacterial properties, which was then applied for rabbit meat preservation at 4 °C for 16 days of storage. CT/BYW/AgNPs1.5%-packed sample had lower values of TVB-N, TBARS, TVC, and pH with greater retention of color properties compared to the control sample, which describes its ability to maintain meat freshness.

MultiTrans: Multi-branch transformer network for medical image segmentation.

BACKGROUND AND OBJECTIVE: Transformer, which is notable for its ability of global context modeling, has been used to remedy the shortcomings of Convolutional neural networks (CNN) and break its dominance in medical image segmentation. However, the self-attention module is both memory and computational inefficient, so many methods have to build their Transformer branch upon largely downsampled feature maps or adopt the tokenized image patches to fit their model into accessible GPUs. This patch-wise operation restricts the network in extracting pixel-level intrinsic structural or dependencies inside each patch, hurting the performance of pixel-level classification tasks. METHODS: To tackle these issues, we propose a memory- and computation-efficient self-attention module to enable reasoning on relatively high-resolution features, promoting the efficiency of learning global information while effective grasping fine spatial details. Furthermore, we design a novel Multi-Branch Transformer (MultiTrans) architecture to provide hierarchical features for handling objects with variable shapes and sizes in medical images. By building four parallel Transformer branches on different levels of CNN, our hybrid network aggregates both multi-scale global contexts and multi-scale local features. RESULTS: MultiTrans achieves the highest segmentation accuracy on three medical image datasets with different modalities: Synapse, ACDC and M&Ms. Compared to the Standard Self-Attention (SSA), the proposed Efficient Self-Attention (ESA) can largely reduce the training memory and computational complexity while even slightly improve the accuracy. Specifically, the training memory cost, FLOPs and Params of our ESA are 18.77%, 20.68% and 74.07% of the SSA. CONCLUSIONS: Experiments on three medical image datasets demonstrate the generality and robustness of the designed network. The ablation study shows the efficiency and effectiveness of our proposed ESA. Code is available at: https://github.com/Yanhua-Zhang/MultiTrans-extension.

Membralin is required for maize development and defines a branch of the endoplasmic reticulum-associated degradation pathway in plants.

Endoplasmic reticulum (ER)-associated degradation (ERAD) plays key roles in controlling protein levels and quality in eukaryotes. The Ring Finger Protein 185 (RNF185)/membralin ubiquitin ligase complex was recently identified as a branch in mammals and is essential for neuronal function, but its function in plant development is unknown. Here, we report the map-based cloning and characterization of Narrow Leaf and Dwarfism 1 (NLD1), which encodes the ER membrane-localized protein membralin and specifically interacts with maize homologs of RNF185 and related components. The nld1 mutant shows defective leaf and root development due to reduced cell number. The defects of nld1 were largely restored by expressing membralin genes from Arabidopsis thaliana and mice, highlighting the conserved roles of membralin proteins in animals and plants. The excessive accumulation of ß-hydroxy ß-methylglutaryl-CoA reductase in nld1 indicates that the enzyme is a membralin-mediated ERAD target. The activation of bZIP60 mRNA splicing-related unfolded protein response signaling and marker gene expression in nld1, as well as DNA fragment and cell viability assays, indicate that membralin deficiency induces ER stress and cell death in maize, thereby affecting organogenesis. Our findings uncover the conserved, indispensable role of the membralin-mediated branch of the ERAD pathway in plants. In addition, ZmNLD1 contributes to plant architecture in a dose-dependent manner, which can serve as a potential target for genetic engineering to shape ideal plant architecture, thereby enhancing high-density maize yields.

Silencing PCMT1 enhances the sensitivity of breast cancer cells to paclitaxel through the PI3K/Akt/STMN1 pathway.

This study aimed to investigate whether silencing Protein L-isoaspartate (D-aspartate) O-methyltransferase (PCMT1) expression can enhance the sensitivity of breast cancer cells to paclitaxel and its possible mechanism. Tumor tissues and adjacent histologically normal tissues were collected from patients with breast cancer admitted to our hospital. Human normal breast epithelial cells MCF10A, human breast cancer cells MCF-7, and paclitaxel-resistant breast cancer cells MCF-7/PR were purchased. MCF-7/PR cells were further grouped into negative control (NC) group, si-PCMT1 group (transfected with si-PCMT1), 740Y-P group (treated with 740Y-P, an activator of phosphatidylinositol 3-kinase (PI3K)/ v-Akt Murine Thymoma Viral Oncogene (AKT) signaling pathway), and si-PCMT1 + 740Y-P group (transfected with si-PCMT1 and then treated with 740Y-P). The expression level of PCMT1 in tissues and cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot analysis was used to detect the protein expression level of PCMT1 in tissues and cells as well as the protein level of p-PI3K, PI3K, p-Akt, Akt, and Stathmin1 (STMN1) in cells. 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and colony formation assays were used to determine cell viability, scratch assay was used to assess the migration ability of cells, and Transwell assay was used to assess the invasion ability of cells. The expression of PCMT1 was remarkably up-regulated in breast cancer tissues and MCF-7/PR cells. Silencing PCMT1 expression significantly inhibited the proliferation, migration, and invasion of MCF-7/PR cells, and alleviated the resistance of cancer cells to paclitaxel. Additionally, silencing PCMT1 expression also inhibited the activation of PI3K/Akt/STMN1 pathway in MCF-7/PR cells, while activating PI3K/Akt/STMN1 pathway significantly reversed the effect of silencing PCMT1 expression on MCF-7/PR cells. PCMT1 is highly expressed in breast cancer tissues and MCF-7/PR cells, and silencing PCMT1 expression can not only inhibit the development of breast cancer but also enhance paclitaxel sensitivity. Its mechanism of action may be achieved by inhibiting PI3K/Akt/STMN1 signaling.

3D MR neurography with gadolinium contrast to improve the visualization of pelvic nerves and the branches.

Objective: To evaluate the effectiveness of 3D NerveVIEW sequence with gadolinium contrast on the visualization of pelvic nerves and their branches compared to that without contrast. Methods: Participants were scanned twice using 3D NerveVIEW sequence with and without gadolinium contrast to acquire pelvic nerve images. The signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and contrast ratio of the nerves were calculated and compared to determine the quality of images. To subjectively assess, using a 3-point scale, branch nerves critical to therapeutic decision-making, including the pelvic splanchnic nerve and pelvic plexus, the superior gluteal nerve, and the pudendal nerve. Results: In the 32 eligible participants after using contrast, the CNRs of the images of nerve-to-bone and nerve-to-vessel significantly increased (p < 0.05). The CR of the images with contrast of all nerve-to-surrounding tissues (i.e., bone, muscle, blood vessels, and fat) were also found significantly higher (p < 0.05). The assessment of observers also shows higher scores for images with contrast compared to images without contrast. Conclusion: The 3D NerveVIEW sequence combined with gadolinium contrast improved vascular suppression, increased the contrast between pelvic nerves and surrounding tissue, and enhanced the visualization of nerves and their branches. This study may be helpful for the technically challenging preoperative planning of pelvic diseases surgery.

Progress of single-cell RNA sequencing combined with spatial transcriptomics in tumour microenvironment and treatment of pancreatic cancer.

In recent years, single-cell analyses have revealed the heterogeneity of the tumour microenvironment (TME) at the genomic, transcriptomic, and proteomic levels, further improving our understanding of the mechanisms of tumour development. Single-cell RNA sequencing (scRNA-seq) technology allow analysis of the transcriptome at the single-cell level and have unprecedented potential for exploration of the characteristics involved in tumour development and progression. These techniques allow analysis of transcript sequences at higher resolution, thereby increasing our understanding of the diversity of cells found in the tumour microenvironment and how these cells interact in complex tumour tissue. Although scRNA-seq has emerged as an important tool for studying the tumour microenvironment in recent years, it cannot be used to analyse spatial information for cells. In this regard, spatial transcriptomics (ST) approaches allow researchers to understand the functions of individual cells in complex multicellular organisms by understanding their physical location in tissue sections. In particular, in related research on tumour heterogeneity, ST is an excellent complementary approach to scRNA-seq, constituting a new method for further exploration of tumour heterogeneity, and this approach can also provide unprecedented insight into the development of treatments for pancreatic cancer (PC). In this review, based on the methods of scRNA-seq and ST analyses, research progress on the tumour microenvironment and treatment of pancreatic cancer is further explained.

Token-Mixer: Bind Image and Text in One Embedding Space for Medical Image Reporting.

Medical image reporting focused on automatically generating the diagnostic reports from medical images has garnered growing research attention. In this task, learning cross-modal alignment between images and reports is crucial. However, the exposure bias problem in autoregressive text generation poses a notable challenge, as the model is optimized by a word-level loss function using the teacher-forcing strategy. To this end, we propose a novel Token-Mixer framework that learns to bind image and text in one embedding space for medical image reporting. Concretely, Token-Mixer enhances the cross-modal alignment by matching image-to-text generation with text-to-text generation that suffers less from exposure bias. The framework contains an image encoder, a text encoder and a text decoder. In training, images and paired reports are first encoded into image tokens and text tokens, and these tokens are randomly mixed to form the mixed tokens. Then, the text decoder accepts image tokens, text tokens or mixed tokens as prompt tokens and conducts text generation for network optimization. Furthermore, we introduce a tailored text decoder and an alternative training strategy that well integrate with our Token-Mixer framework. Extensive experiments across three publicly available datasets demonstrate Token-Mixer successfully enhances the image-text alignment and thereby attains a state-of-the-art performance. Related codes are available at https://github.com/yangyan22/Token-Mixer.

Evaluation of the novel endophytic fungus Chaetomium ascotrichoides 1-24-2 from Pinus massoniana as a biocontrol agent against pine wilt disease caused by Bursaphelenchus xylophilus.

BACKGROUND: Bursaphelenchus xylophilus, the causative agent of pine wilt disease (PWD), is an ever-increasing threat to Pinus forests worldwide. This study aimed to develop biological control of PWD by the application of endophytic fungi isolated from healthy pine trees. RESULTS: We successfully isolated a novel endophytic fungal strain 1-24-2 from branches of healthy Pinus massoniana. The culture filtrates (CFs) of strain 1-24-2 exhibited strong nematicidal activity against Bursaphelenchus xylophilus, with a corrected mortality rate of 99.00%. Based on the morphological and molecular characteristics, the isolated strain 1-24-2 was identified as Chaetomium ascotrichoides. In the in-planta assay, pine seedlings (2-years-old) treated with 1-24-2 CFs + pine wood nematode (T2) showed a significant control effect of 80%. A total of 24 toxic compounds were first identified from 1-24-2 CFs through gas chromatography-mass spectrometry (GC-MS) analysis, from which O-methylisourea, 2-chlorobenzothiazole, and 4,5,6-trihydroxy-7-methylphthalide showed robust binding sites at Tyr119 against phosphoethanolamine methyltransferase (PMT) protein of Bursaphelenchus xylophilus by molecular docking approach and could be used as potential compounds for developing effective nematicides. Interestingly, strain 1-24-2 produces toxic volatile organic compounds (VOCs), which disturb the natural development process of B. xylophilus, whose total number decreased by up to 83.32% in the treatment group as compared to control and also reduced Botrytis cinerea growth by up to 71.01%. CONCLUSION: Our results highlight the potential of C. ascotrichoides 1-24-2 as a promising biocontrol agent with solid nematicidal activity against B. xylophilus. This is the first report of C. ascotrichoides isolated from P. massoniana exhibiting strong biocontrol potential against B. xylophilus in the world. © 2024 Society of Chemical Industry.

Cross-Sectional and Prospective Association of Serum 25-Hydroxyvitamin D with Gut Mycobiota during Pregnancy among Women with Gestational Diabetes.

SCOPE: Little is known about the effect of blood vitamin D status on the gut mycobiota (i.e., fungi), a crucial component of the gut microbial ecosystem. The study aims to explore the association between 25-hydroxyvitamin D [25(OH)D] and gut mycobiota and to investigate the link between the identified mycobial features and blood glycemic traits. METHODS AND RESULTS: The study examines the association between serum 25(OH)D levels and the gut mycobiota in the Westlake Precision Birth Cohort, which includes pregnant women with gestational diabetes mellitus (GDM). The study develops a genetic risk score (GRS) for 25(OH)D to validate the observational results. In both the prospective and cross-sectional analyses, the vitamin D is associated with gut mycobiota diversity. Specifically, the abundance of Saccharomyces is significantly lower in the vitamin D-sufficient group than in the vitamin D-deficient group. The GRS of 25(OH)D is inversely associated with the abundance of Saccharomyces. Moreover, the Saccharomyces is positively associated with blood glucose levels. CONCLUSION: Blood vitamin D status is associated with the diversity and composition of gut mycobiota in women with GDM, which may provide new insights into the mechanistic understanding of the relationship between vitamin D levels and metabolic health.

Evolutionary screening of precision oncology biomarkers and its applications in prognostic model construction.

Biomarker screening is critical for precision oncology. However, one of the main challenges in precision oncology is that the screened biomarkers often fail to achieve the expected clinical effects and are rarely approved by regulatory authorities. Considering the close association between cancer pathogenesis and the evolutionary events of organisms, we first explored the evolutionary feature underlying clinically approved biomarkers, and two evolutionary features of approved biomarkers (Ohnologs and specific evolutionary stages of genes) were identified. Subsequently, we utilized evolutionary features for screening potential prognostic biomarkers in four common cancers: head and neck squamous cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, and lung squamous cell carcinoma. Finally, we constructed an evolution-strengthened prognostic model (ESPM) for cancers. These models can predict cancer patients' survival time across different cancer cohorts effectively and perform better than conventional models. In summary, our study highlights the application potentials of evolutionary information in precision oncology biomarker screening.

Specific surface area of mannitol rather than particle size dominant the dissolution rate of poorly water-soluble drug tablets: A study of binary mixture.

The dissolution behavior of tablets, particularly those containing poorly water-soluble drugs, is a critical factor in determining their absorption and therapeutic efficacy. Traditionally, the particle size of excipients has been considered a key property affecting tablet dissolution. However, lurasidone hydrochloride (LH) tablets prepared by similar particle size mannitol, namely M200 (D90 = 209.68 ±â€¯1.42 µm) and 160C (D90 = 195.38 ±â€¯6.87 µm), exhibiting significant differences in their dissolution behavior. In order to find the fundamental influential factors of mannitol influencing the dissolution of LH tablets, the properties (particle size, water content, true density, bulk density, tapped density, specific surface area, circularity, surface free energy, mechanical properties and flowability) of five grades mannitol including M200 and 160C were investigated. Principal component analysis (PCA) was used to establish a relationship between mannitol properties and the dissolution behavior of LH. The results demonstrated that specific surface area (SSA) emerged as the key property influencing the dissolution of LH tablets. Moreover, our investigation based on the percolation theory provided further insights that the SSA of mannitol influences the probability of LH-LH bonding and LH infinite cluster formation, resulting in the different percolation threshold states, then led to different dissolution behaviors. Importantly, it is worth noting that these findings do not invalidate previous conclusions, as reducing particle size generally increases SSA, thereby affecting the percolation threshold and dissolution behavior of LH. Instead, this study provides a deeper understanding of the underlying role played by excipient SSA in the dissolution of drug tablets. This study provides valuable guidance for the development of novel excipients aimed at improving drug dissolution functionality.