Transplantation of the LRP1high subpopulation of human umbilical cord-derived mesenchymal stem cells improves ovarian function in mice with premature ovarian failure and aged mice.

BACKGROUND: Premature ovarian failure (POF) has a profound impact on female reproductive and psychological health. In recent years, the transplantation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) has demonstrated unprecedented potential in the treatment of POF. However, the heterogeneity of human UC-MSCs remains a challenge for their large-scale clinical application. Therefore, it is imperative to identify specific subpopulations within UC-MSCs that possess the capability to improve ovarian function, with the aim of reducing the uncertainty arising from the heterogeneity while achieving more effective treatment of POF. METHODS: 10 × Genomics was performed to investigate the heterogeneity of human UC-MSCs. We used LRP1 as a marker and distinguished the potential therapeutic subpopulation by flow cytometry, and determined its secretory functions. Unsorted UC-MSCs, LRP1high and LRP1low subpopulation was transplanted under the ovarian capsules of aged mice and CTX-induced POF mice, and therapeutic effects was evaluated by assessing hormone levels, estrous cycles, follicle counts, and embryo numbers. RNA sequencing on mouse oocytes and granulosa cells after transplantation was performed to explore the mechanism of LRP1high subpopulation on mouse oocytes and granulosa cells. RESULTS: We identified three distinct functional subtypes, including mesenchymal stem cells, multilymphoid progenitor cells and trophoblasts. Additionally, we identified the LRP1high subpopulation, which improved ovarian function in aged and POF mice. We elucidated the unique secretory functions of the LRP1high subpopulation, capable of secreting various chemokines, cytokines, and growth factors. Furthermore, LRP1 plays a crucial role in regulating the ovarian microenvironment, including tissue repair and extracellular matrix remodeling. Consistent with its functions, the transcriptomes of oocytes and granulosa cells after transplantation revealed that the LRP1high subpopulation improves ovarian function by modulating the extracellular matrix of oocytes, NAD metabolism, and mitochondrial function in granulosa cells. CONCLUSION: Through exploration of the heterogeneity of UC-MSCs, we identified the LRP1high subpopulation capable of improving ovarian function in aged and POF mice by secreting various factors and remodeling the extracellular matrix. This study provides new insights into the targeted exploration of human UC-MSCs in the precise treatment of POF.

Progress in Identification of UDP-Glycosyltransferases for Ginsenoside Biosynthesis.

Ginsenosides, the primary pharmacologically active constituents of the Panax genus, have demonstrated a variety of medicinal properties, including anticardiovascular disease, cytotoxic, antiaging, and antidiabetes effects. However, the low concentration of ginsenosides in plants and the challenges associated with their extraction impede the advancement and application of ginsenosides. Heterologous biosynthesis represents a promising strategy for the targeted production of these natural active compounds. As representative triterpenoids, the biosynthetic pathway of the aglycone skeletons of ginsenosides has been successfully decoded. While the sugar moiety is vital for the structural diversity and pharmacological activity of ginsenosides, the mining of uridine diphosphate-dependent glycosyltransferases (UGTs) involved in ginsenoside biosynthesis has attracted a lot of attention and made great progress in recent years. In this paper, we summarize the identification and functional study of UGTs responsible for ginsenoside synthesis in both plants, such as Panax ginseng and Gynostemma pentaphyllum, and microorganisms including Bacillus subtilis and Saccharomyces cerevisiae. The UGT-related microbial cell factories for large-scale ginsenoside production are also mentioned. Additionally, we delve into strategies for UGT mining, particularly potential rapid screening or identification methods, providing insights and prospects. This review provides insights into the study of other unknown glycosyltransferases as candidate genetic elements for the heterologous biosynthesis of rare ginsenosides.

Adaptation in Unstable Environments and Global Gene Losses: Small but Stable Gene Networks by the May-Wigner Theory.

Although gene loss is common in evolution, it remains unclear whether it is an adaptive process. In a survey of seven major mangrove clades that are woody plants in the intertidal zones of daily environmental perturbations, we noticed that they generally evolved reduced gene numbers. We then focused on the largest clade of Rhizophoreae and observed the continual gene set reduction in each of the eight species. A great majority of gene losses are concentrated on environmental interaction processes, presumably to cope with the constant fluctuations in the tidal environments. Genes of the general processes for woody plants are largely retained. In particular, fewer gene losses are found in physiological traits such as viviparous seeds, high salinity, and high tannin content. Given the broad and continual genome reductions, we propose the May-Wigner theory (MWT) of system stability as a possible mechanism. In MWT, the most effective solution for buffering continual perturbations is to reduce the size of the system (or to weaken the total genic interactions). Mangroves are unique as immovable inhabitants of the compound environments in the land-sea interface, where environmental gradients (such as salinity) fluctuate constantly, often drastically. Extending MWT to gene regulatory network (GRN), computer simulations and transcriptome analyses support the stabilizing effects of smaller gene sets in mangroves vis-à-vis inland plants. In summary, we show the adaptive significance of gene losses in mangrove plants, including the specific role of promoting phenotype innovation and a general role in stabilizing GRN in unstable environments as predicted by MWT.

Genomic analysis of Nypa fruticans elucidates its intertidal adaptations and early palm evolution.

Nypa fruticans (Wurmb), a mangrove palm species with origins dating back to the Late Cretaceous period, is a unique species for investigating long-term adaptation strategies to intertidal environments and the early evolution of palms. Here, we present a chromosome-level genome sequence and assembly for N. fruticans. We integrated the genomes of N. fruticans and other palm family members for a comparative genomic analysis, which confirmed that the common ancestor of all palms experienced a whole-genome duplication event around 89 million years ago, shaping the distinctive characteristics observed in this clade. We also inferred a low mutation rate for the N. fruticans genome, which underwent strong purifying selection and evolved slowly, thus contributing to its stability over a long evolutionary period. Moreover, ancient duplicates were preferentially retained, with critical genes having experienced positive selection, enhancing waterlogging tolerance in N. fruticans. Furthermore, we discovered that the pseudogenization of Early Methionine-labelled 1 (EM1) and EM6 in N. fruticans underly its crypto-vivipary characteristics, reflecting its intertidal adaptation. Our study provides valuable genomic insights into the evolutionary history, genome stability, and adaptive evolution of the mangrove palm. Our results also shed light on the long-term adaptation of this species and contribute to our understanding of the evolutionary dynamics in the palm family.

Determining the nutritional values of new corn varieties on pigs and broilers.

The objective of this study was to evaluate the nutritional values of three new corn varieties (high-iron corn, cadmium-resistant corn, low-phytate phosphorus corn) cultivated with molecular marker-assisted selection breeding technique fed to growing pigs and broilers. Exp. 1 was conducted to compare the nutritional values of high-iron corn, high-chromium corn, low-phytate phosphorus corn and conventional corn fed to growing pigs based on a 15 × 2 Youden square design. Exp.2 was conducted to compare the nutritional values of high-iron corn, low-phytate phosphorus corn and conventional corn fed to broilers based on a completely randomized design. Parameters including nutrient digestibility, available energy and amino acids, and mineral deposition were measured. The results shows that the iron content in the high-iron corn and the cadmium content in the cadmium-resistant corn were 29.608 mg/kg and 0.0057 mg/kg, respectively, both were greater than those in the other three kinds of corns. When fed to growing pigs, the neutral detergent fiber digestibility of the high-iron corn group was lower than that of the conventional corn group (p < 0.05), and the acid detergent fiber digestibility of the high-iron group and the low-phytate phosphorus corn group was lower than that of the conventional corn group (p < 0.01). In addition, the digestible energy value of the high-iron corn in growing pigs was lower than that of the conventional corn (p < 0.05). When fed to broilers, it was observed that the tibia length of the low-phytate phosphorus corn group and the high-iron corn group was lower than that of the conventional corn group (p < 0.05). Moreover, the iron emission in feces of broilers fed the low-phytate phosphorus corn was lower than those fed the conventional corn and the high-iron corn (p < 0.05). In conclusion, modern breeding techniques could provide new plant ingredients which have potential benefits to pig and broiler production, but the comprehensive effects may be better when applied to growing pigs considering growth performance and environment effects. The breeding techniques related to the current study rarely changed the available energy values of the corn in growing pigs and broilers.

Genomic evidence for rediploidization and adaptive evolution following the whole-genome triplication.

Whole-genome duplication (WGD), or polyploidy, events are widespread and significant in the evolutionary history of angiosperms. However, empirical evidence for rediploidization, the major process where polyploids give rise to diploid descendants, is still lacking at the genomic level. Here we present chromosome-scale genomes of the mangrove tree Sonneratia alba and the related inland plant Lagerstroemia speciosa. Their common ancestor has experienced a whole-genome triplication (WGT) approximately 64 million years ago coinciding with a period of dramatic global climate change. Sonneratia, adapting mangrove habitats, experienced extensive chromosome rearrangements post-WGT. We observe the WGT retentions display sequence and expression divergence, suggesting potential neo- and sub-functionalization. Strong selection acting on three-copy retentions indicates adaptive value in response to new environments. To elucidate the role of ploidy changes in genome evolution, we improve a model of the polyploidization-rediploidization process based on genomic evidence, contributing to the understanding of adaptive evolution during climate change.

A portable intelligent hydrogel platform for multicolor visual detection of HAase.

Hyaluronidase (HAase) is an important endoglycosidase involved in numerous physiological and pathological processes, such as apoptosis, senescence, and cancer progression. Simple, convenient, and sensitive detection of HAase is important for clinical diagnosis. Herein, an easy-to-operate multicolor visual sensing strategy was developed for HAase determination. The proposed sensor was composed of an enzyme-responsive hydrogel and a nanochromogenic system (gold nanobipyramids (AuNBPs)). The enzyme-responsive hydrogel, formed by polyethyleneimine-hyaluronic acid (PEI-HA), was specifically hydrolyzed with HAase, leading to the release of platinum nanoparticles (PtNPs). Subsequently, PtNPs catalyzed the mixed system of 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2 to produce TMB2+ under acidic conditions. Then, TMB2+ effectively etched the AuNBPs and resulted in morphological changes in the AuNBPs, accompanied by a blueshift in the localized surface plasmon resonance peak and vibrant colors. Therefore, HAase can be semiquantitatively determined by directly observing the color change of AuNBPs with the naked eye. On the basis of this, the method has a linear detection range of HAase concentrations between 0.6 and 40 U/mL, with a detection limit of 0.3 U/mL. In addition, our designed multicolor biosensor successfully detected the concentration of HAase in human serum samples. The results showed no obvious difference between this method and enzyme-linked immunosorbent assay, indicating the good accuracy and usability of the suggested method.

Investigation of the association between the Toll-like receptor 1 rs4833095 variation and gastric adenocarcinoma recurrence.

BACKGROUND: Toll-like receptors (TLRs) are a family of transmembrane receptors that play key roles in identifying invading pathogens and activating innate immunity. TLR1 has been reported to be associated with the risk of gastric cancer (GC) but that was based on only a simple statistical analysis. METHODS: We genotyped the TLR1 in 526 GC patients to investigate the association between the variation and gastric cancer survival by the multiplex polymerase chain reaction and sequencing method. The rs4833095 variation (chr4:38798089 [GRCh38. p14], T > C) in the TLR1 gene was genotyped in 526 patients who underwent GC resection. The associations between genotype, survival, and recurrence were investigated. The potential role of TLR1 in stomach cancer was investigated using clinical data from formalin-fixed, paraffin-embedded tissue samples. RESULTS: Patients with the T/C and C/C genotypes of rs4833095 had a lower risk of recurrence than those with the T/T genotype. Recurrence-free periods were substantially longer in patients with the T/C or C/C genotypes (22.6 and 22.3 months, respectively) than in those with the T/T genotype (20.7 months). Patients with the T/C or C/C genotype, low expression levels of VEGF1, high expression levels of ERBB2 and ERCC1, the absence of cancer nodules, a tumor size of less than 5 cm, and poor differentiation had a considerably reduced risk of recurrence. CONCLUSIONS: TLR1 rs4833095 was correlated with the postresection prognosis of patients with gastric cancer, suggesting that TLR1 may have a role in the onset or progression of gastric cancer.

Diagnostic significance of HRCT imaging features in adult mycoplasma pneumonia: a retrospective study.

Mycoplasma pneumoniae pneumonia (MPP) often overlaps with the clinical manifestations and chest imaging manifestations of other types of community-acquired pneumonia (CAP). We retrospectively analyzed the clinical and imaging data of a group of patients with CAP, summarized their clinical and imaging characteristics, and discussed the diagnostic significance of their certain HRCT findings. The HRCT findings of CAP researched in our study included tree-in-bud sign (TIB), ground-glass opacity (GGO), tree fog sign (TIB + GGO), bronchial wall thickening, air-bronchogram, pleural effusion and cavity. The HRCT findings of all cases were analyzed. Among the 200 cases of MPP, 174 cases showed the TIB, 193 showed the GGO, 175 showed the tree fog sign, 181 lacked air-bronchogram. In case taking the tree fog sign and lack of air-bronchogram simultaneously as an index to distinguish MPP from OCAP, the sensitivity was 87.5%, the specificity was 97.5%, the accuracy was 92.5%. This study showed that that specific HRCT findings could be used to distinguish MPP from OCAP. The combined HRCT findings including the tree fog sign and lacked air-bronchogram simultaneously would contribute to a more accurate diagnosis of MPP.

Transcription Factor MITF Inhibits the Transcription of CPT1B to Regulate Fatty Acid ß-Oxidation and Thus Affects Stemness in Lung Adenocarcinoma Cells.

INTRODUCTION: Cancer stem cells (CSCs) play critical roles in lung adenocarcinoma (LUAD) progression, and fatty acid oxidation is key for CSC growth and survival. Therefore, investigating the molecular mechanisms regulating fatty acid ß-oxidation in LUAD is important for its treatment. METHODS: Bioinformatics analysis assessed CPT1B and MITF expression and their correlation in LUAD tissues, as well as the pathways enriched by CPT1B. qRT-PCR assessed expression of CPT1B and MITF, while CCK-8 and sphere-forming assays were used to measure cell viability and stemness, respectively. Dual staining detected lipid accumulation, while kits were used to measure fatty acid ß-oxidation and glycerol content. qRT-PCR was used to assay expression of lipid oxidation genes. Western blot was used to examine expression of stem cell-related markers. Dual-luciferase assay and ChIP assay were used to verify the binding relationship between MITF and CPT1B. RESULTS: CPT1B was found to be highly expressed in LUAD and enriched in linoleic acid metabolism pathway and α-linolenic acid metabolism pathway. Functional experiments showed that CPT1B could promote stemness in LUAD cells by regulating fatty acid ß-oxidation. Additionally, CPT1B was found to be regulated by the upstream transcription factor MITF, which was lowly expressed in LUAD and could downregulate CPT1B expression. Rescue experiments revealed that CPT1B/MITF axis could affect stemness in LUAD cells by regulating fatty acid ß-oxidation. CONCLUSION: Transcription factor MITF inhibited transcription of CPT1B to regulate fatty acid ß-oxidation, thereby suppressing stemness in LUAD cells. MITF and CPT1B may become new targets for LUAD.

Hsa_circ_0013561 promotes epithelial-mesenchymal transition and tumor progression by regulating ANXA2 via miR-23b-3p in ovarian cancer.

Our preliminary experiment discovered that hsa_circ_0013561 was aberrantly expressed in OC. However, the underlying mechanism is unclear. The expression of hsa_circ_0013561 in OC cells and tissues was detected by RT-qPCR and fluorescence in situ hybridization. The effects of hsa_circ_0013561 on the proliferation and metastasis of OC were explored by functional experiments such as cell counting kit-8, transwell, and tumor xenograft models. To mechanistically understand the regulatory role of hsa_circ_0013561, bioinformatics analysis, Western blot, luciferase reporter assay, and a series of rescue experiments were applied. We found that the hsa_circ_0013561 expression was elevated in OC cells and tissues, and was correlated with metastasis formation. Downregulation of hsa_circ_0013561 suppressed the proliferation and migration of OC cells both in vitro and in vivo. Regarding the interactions of hsa_circ_0013561, the luciferase reporter assay verified that miR-23b-3p and Annexin A2 (ANXA2) were its downstream targets. MiR-23b-3p inhibition or ANXA2 overexpression reversed OC cell proliferation, migration, and epithelial-mesenchymal transition (EMT) post-hsa_circ_0013561 silencing. Moreover, ANXA2 overexpression also reversed OC cell migration, proliferation, and EMT after miR-23b-3p upregulation. Our data suggest that hsa_circ_0013561 increases the expression of ANXA2 by regulating miR-23b-3p competitively, resulting in EMT and metastasis of OC. Thus, hsa_circ_0013561 may serve as a novel oncogenic biomarker for OC progression.

Hybridization chain reaction assisted multicolor immunosensor for sensitively detection of human chorionic gonadotropin.

The level of human chorionic gonadotropin (HCG) is an important indicator for early pregnancy, pregnancy-related diseases trophoblastic diseases and even cancer diagnosis. Therefore, sensitive detection of HCG has crucial significance in clinical, especially in gynaecology and obstetrics. Herein, a hybridization chain reaction (HCR) assisted multicolor immunosensor have been developed for HCG analysis. The proposed method introduced HCR after the immunoreaction between antibody and HCG protein, and produced long double strand DNA (dsDNA) that contain biotin sites. The streptavidin-horseradish peroxidase was linked on the dsDNA by the interaction between biotin and streptavidin, and can further mediated gold nanobipyramids (Au NBPs) etching. The localized surface plasmon resonance absorption peaks of Au NBPs blue shift and accompanied a vivid color change after etching effect. Based on this color change, HCG could be qualitative and semi-quantitative detected. Because of the introduction of HCR and enzyme amplification technique, the proposed method exhibited high sensitivity with a linear range of 0.1-2000 pg/mL and limit of detection (LOD) of 0.1 pg/mL. Finally, the proposed immunosensor was used to detect clinical serum samples. The results show there are no significant differences between clinical results and the test results by this method, indicating the practicability of the proposed method.

The evolution history of an allotetraploid mangrove tree analysed with a new tool Allo4D.

Mangrove species are broadly classified as true mangroves and mangrove associates. The latter are amphibious plants that can survive in the intertidal zone and reproduce naturally in terrestrial environments. Their widespread distribution and extensive adaptability make them ideal research materials for exploring adaptive evolution. In this study, we de novo assembled two genomes of mangrove associates (the allotetraploid Barringtonia racemosa (2n = 4x = 52) and diploid Barringtonia asiatica (2n = 2x = 26)) to investigate the role of allopolyploidy in the evolutionary history of mangrove species. We developed a new allotetraploid-dividing tool Allo4D to distinguish between allotetraploid scaffold-scale subgenomes and verified its accuracy and reliability using real and simulated data. According to the two subgenomes of allotetraploid B. racemosa divided using Allo4D, the allopolyploidization event was estimated to have occurred approximately one million years ago (Mya). We found that B. racemosa, B. asiatica, and Diospyros lotus shared a whole genome duplication (WGD) event during the K-Pg (Cretaceous-Paleozoic) period. K-Pg WGD and recent allopolyploidization events contributed to the speciation of B. racemosa and its adaptation to coastal habitats. We found that genes in the glucosinolates (GSLs) pathway, an essential pathway in response to various biotic and abiotic stresses, expanded rapidly in B. racemosa during polyploidization. In summary, this study provides a typical example of the adaptation of allopolyploid plants to extreme environmental conditions. The newly developed tool, Allo4D, can effectively divide allotetraploid subgenomes and explore the evolutionary history of polyploid plants, especially for species whose ancestors are unknown or extinct.

Integration of multiomics analysis to reveal the major pathways of vitamin A deficiency aggravates acute respiratory distress syndrome in neonatal rats.

Acute respiratory distress syndrome (ARDS) is a major disease that threatens the life and health of neonates. Vitamin A (VA) can participate in early fetal lung development and affect lung immune function. Researches revealed that the serum VA level in premature infants with ARDS was lower than that in premature infants without ARDS of the same gestational age, and premature infants with VA deficiency (VAD) were more likely to develop ARDS. Moreover, the VA levels can be used as a predictor of the development and severity of neonatal ARDS. However, the critical question here is; Does ARDS develop due to VAD in these systemic diseases? Or does ARDS develop because these diseases cause VAD? We hypothesize that VAD may aggravate neonatal ARDS by affecting immunity, metabolism, barriers and other pathways. In this article, we used multiomics analysis to find that VAD may aggravate ARDS mainly through the Fc epsilon RI signaling pathway, the HIF-1 signaling pathway, glutathione metabolism, and valine, leucine and isoleucine degradation signaling pathways, which may provide the molecular pathogenic mechanism behind the pathology of VAD-aggravated ARDS and can also provide potential molecular targets for subsequent research on ARDS.

Covalent organic framework-based immunosensor to detect plasma Latexin reveals novel biomarker for coronary artery diseases.

It is a great challenge to develop an efficient and rapid method to detect of biomarkers of cardiovascular disease. In this research, a differential pulse voltammetry (DPV)-based ultrasensitive immunosensor for the detection of plasma Latexin (LXN) has been established. With the aim to increase the surface area of the bare glassy carbon electrode (GCE), multi-walled carbon nanotube-graphene oxide has been developed. Covalent organic frameworks (COFs) are dropped with gold nanoparticles (AuNPs), secondary antibody and thionine (Thi-Ab2-Au-COFs) act as the signal probe with high electronic conductivity. Under the ideal conditions, the immunosensor displayed a broad linear response range from 0.01 ng mL-1 to 100 ng mL-1, with a detection limit of 50 pg mL-1 (S/N = 3). The immunosensor also demonstrates outstanding sensitivity, repeatability, and stability. Finally, we utilized the designed immunosensor to detect plasma LXN in coronary artery disease (CAD) patients, and the data showed that plasma LXN was significantly increased in CAD patients with a good performance of ROCAUC (AUC 0.871, 95 % CI 0.725-1.0, p = 0.002), indicating plasma LXN is a potential biomarker of cardiovascular disease. This immunosensor is a promising strategy for screening CAD patients in clinical practice.

The efficacy and feasibility of neoadjuvant immunotherapy plus chemotherapy followed by McKeown minimally invasive oesophagectomy for locally advanced oesophageal squamous cell carcinoma.

Introduction: In immunotherapy, antibodies are activated to block immune checkpoints, resist tumour immunosuppression, shrink tumours and prevent a recurrence. As the science behind tumour immunotherapy continuously develops and improves, neoadjuvant immunotherapy bears more prominent advantages: antigen exposure not only enhances the degree of tumour-specific T-cell response but also prolongs the duration of actions. In this study, we evaluated the efficacy and safety of McKeown minimally invasive oesophagectomy (McKeown MIO) following neoadjuvant immunotherapy combined with chemotherapy (NICT) in patients with locally advanced oesophageal cancer (OC). Patients and Methods: In this retrospective study, 94 patients underwent either NICT or neoadjuvant chemotherapy (NCT) followed by MIO at our institution from January 2020 to October 2022. We assessed the therapy-related adverse events and perioperative outcomes and compared them between the two groups. Results: After completing at least two cycles of neoadjuvant therapy, all patients underwent McKeown MIO with negative margins within 4-7 weeks. Demographic data of the two cohorts were similar. Regarding perioperative characteristics, the median intraoperative blood loss was 50 ml in the NICT group, lower than that of the NCT group (100 ml, P < 0.05). In addition, the NICT group had significantly more harvested lymph nodes than the NCT group (P < 0.05). No significant differences were found in post-operative complications. The rate of objective response rate in the NICT group was higher than that in the NCT group (88.3% vs. 58.8%). Regarding tumour regression, the number of patients with TRG Grades 1-3 in the NICT group was more than that in the NCT. Adverse events experienced by the two groups included anaemia and elevated transaminase. We found no difference in the adverse events between the two groups. Conclusions: This study showed the efficacy and feasibility of NICT followed by McKeown MIO in treating locally advanced OC.

Contrast-enhanced magnetic resonance image segmentation based on improved U-Net and Inception-ResNet in the diagnosis of spinal metastases.

Objective: The objective of this study was to investigate the use of contrast-enhanced magnetic resonance imaging (CE-MRI) combined with radiomics and deep learning technology for the identification of spinal metastases and primary malignant spinal bone tumor. Methods: The region growing algorithm was utilized to segment the lesions, and two parameters were defined based on the region of interest (ROI). Deep learning algorithms were employed: improved U-Net, which utilized CE-MRI parameter maps as input, and used 10 layers of CE images as input. Inception-ResNet model was used to extract relevant features for disease identification and construct a diagnosis classifier. Results: The diagnostic accuracy of radiomics was 0.74, while the average diagnostic accuracy of improved U-Net was 0.98, respectively. the PA of our model is as high as 98.001%. The findings indicate that CE-MRI based radiomics and deep learning have the potential to assist in the differential diagnosis of spinal metastases and primary malignant spinal bone tumor. Conclusion: CE-MRI combined with radiomics and deep learning technology can potentially assist in the differential diagnosis of spinal metastases and primary malignant spinal bone tumor, providing a promising approach for clinical diagnosis.

High-quality genome of a pioneer mangrove Laguncularia racemosa explains its advantages for intertidal zone reforestation.

Ecological restoration of mangrove ecosystems that became susceptible to recent habitat perturbations is crucial for tropical coast conservation. The white mangrove Laguncularia racemosa, a pioneer species inhabiting intertidal environments of the Atlantic East Pacific (AEP) region, has been used for reforestation in China for decades. However, the molecular mechanisms underlying its fast growth and high adaptive potential remain unknown. Using PacBio single-molecule real-time sequencing, we completed a high-quality L. racemosa genome assembly covering 1105 Mb with scaffold N50 of 3.46 Mb. Genomic phylogeny shows that L. racemosa invaded intertidal zones during a period of global warming. Multi-level genomic convergence analyses between L. racemosa and three native dominant mangrove clades show that they experienced convergent changes in genes involved in nutrient absorption and high salinity tolerance. This may explain successful L. racemosa adaptation to stressful intertidal environments after introduction. Without recent whole-genome duplications or activated transposable elements, L. racemosa has retained many tandem gene duplications. Some of them are involved in auxin biosynthesis, intense light stress and cold stress response pathways, associated with L. racemosa's ability to grow fast under high light or cold conditions when used for reforestation. In summary, our study identifies shared mechanisms of intertidal environmental adaptation and unique genetic changes underlying fast growth in mangrove-unfavourable conditions and sheds light on the molecular mechanisms of the white mangrove utility in ecological restoration.

In silico discovery of food-derived phytochemicals against asialoglycoprotein receptor 1 for treatment of hypercholesterolemia: Pharmacophore modeling, molecular docking and molecular dynamics simulation approach.

Hypercholesterolemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD). Successful management of cholesterol metabolism disorders can prevent these ASCVD effectively. Asialoglycoprotein receptor 1 (ASGR1) is the main subtype of sialoglycoprotein receptor, which is specifically expressed in the liver and mediates the endocytosis of blood asialoglycoprotein to lysosome degradation. Recently, ASGR1 has been reported as a new therapeutic target for the treatment of hypercholesterolemia. In this study, the main aim was to identify natural ASGR1 inhibitors from plant food chemicals library through pharmacophore and docking based virtual screening. Total 14 phytochemicals of potential ASGR1 inhibitors were identified, which presented docking affinity higher than control compound through docking based virtual screening. The docking pose showed the top three hits interacted residues were located at active pocket of ASGR1 with hydrogen bonds, hydrophobic interactions and electrostatic interactions. The top three hits (ZINC85664954, ZINC169372863, and ZINC195764535) were then subjected to 200 ns molecular dynamics simulation to evaluate the stability of docked complexes. These results showed that selected phytochemicals bound to ASGR1 with higher stability than control compound. Binding free energy of each docked complex was calculated by the Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) method. The binding free energy of ZINC85664954, ZINC169372863, ZINC195764535, and control-ASGR1 docked complexes were -18.359, -13.303, -14.389, and -6.229 kcal/mol, respectively. This indicated that selected hits bound to ASGR1 with higher affinity than control compound. Network pharmacology analysis shows that these phytochemicals have obvious multiple-effects and can regulate various biochemical pathways related to hypercholesterolemia. Besides, selected phytochemicals have suitable pharmacokinetics properties, suggesting that these compounds may be potential drug candidates. This study may be contributed to rational design of novel ASGR1 inhibitors for treatment of hypercholesterolemia.

Cuproptosis-related signature for clinical prognosis and immunotherapy sensitivity in hepatocellular carcinoma.

BACKGROUND: Copper homeostasis imbalance has been implicated in tumor progression, aggressiveness, and treatment response. However, the precise roles of cuproptosis-related genes (CRGs) in hepatocellular carcinoma (HCC) remain poorly understood. METHODS: In this study, we employed a consensus clustering algorithm to identify distinct molecular subtypes. We then performed Kaplan-Meier analysis and univariate Cox regression analysis to identify prognostic differentially expressed genes. The expression of these genes was subsequently validated using qPCR on fresh-frozen tissues obtained from HCC patients. Moreover, leveraging the TCGA-HCC cohort, we constructed a CRGs-related risk prediction model using the LASSO and multivariate Cox regression analysis. RESULTS: By analyzing the data, we successfully established a CRGs risk prognostic model for HCC patients, comprising five differential genes (CAD, SGCB, TXNRD1, KDR, and MTND4P20). Cox regression analysis revealed that the CRGs risk score could serve as an independent prognostic factor for overall survival (hazard ratio [HR] = 1.308, 95% confidence interval [CI] = 1.200 - 1.426, P < 0.001). The area under the curve (AUC) values of the CRGs-score for predicting 1-year, 3-year, and 5-year survival rates were 0.785, 0.724, and 0.723, respectively. Notably, the expression levels of immune checkpoints (including PD-1, PD-L1, and CTLA4) significantly differed between the low- and high-risk score groups. Furthermore, the low-risk score group displayed increased sensitivity to sorafenib, cisplatin, cyclopamine, nilotinib, salubrinal, and gemcitabine, whereas the high-risk score group exhibited heightened sensitivity to lapatinib, erlotinib, and gefitinib. CONCLUSIONS: Our findings highlight the potential of the CRGs risk score as an independent and promising biomarker for clinical prognosis and immunotherapy sensitivity in HCC patients.