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Abstract β-Lactam antibiotics are a class of antibiotics commonly used to treat bacterial infections. However, the effects of β-lactam antibiotics on term neonatal intestinal flora have not been fully elucidated. Hospitalized full-term newborns receiving β-lactam antibiotics formed the antibiotic group (n = 67), while those without antibiotic treatment comprised the non-antibiotic group (n = 47). A healthy group included healthy full-term newborns (n = 16). Stool samples were collected for 16 S rDNA sequencing to analyze gut microbiota variations. Further investigation was carried out within the β-lactam antibiotic group, exploring the effects of antibiotic use on the newborns’ gut microbiota in relation to the duration and type of antibiotic administration, delivery method, and feeding practices. The antibiotic group exhibited significant difference of microbial community composition compared to the other groups. Genera like Klebsiella, Enterococcus, Streptococcus, Alistipes, and Aeromonas were enriched, while Escherichia-Shigella, Clostridium sensu stricto 1, Bifidobacterium, and Parabacteroides were reduced. Klebsiella negatively correlated with Escherichia-Shigella, positively with Enterobacter, while Escherichia-Shigella negatively correlated with Enterococcus and Streptococcus. Regardless of neonatal age, β-lactam antibiotics induced an elevated abundance of Klebsiella and Enterococcus. The impact on gut microbiota varied with the duration and type of antibiotic (cefotaxime or ampicillin/sulbactam). Compared to vaginal delivery, cesarean delivery after β-lactam treatment heightened the abundance of Klebsiella, Enterobacteriaceae_Unclassified, Lactobacillales_Unclassified, and Pectobacterium. Feeding patterns minimally influenced β-lactam-induced alterations. In conclusion, β-lactam antibiotic treatment for neonatal pneumonia and sepsis markedly disrupted intestinal microbiota, favoring Klebsiella, Enterococcus, Streptococcus, Alistipes, and Aeromonas. The impact of β-lactam varied by duration, type, and delivery method, emphasizing heightened disruptions post-cesarean delivery.

Abstract The deltoid muscle and rotator cuff tissue are structural components that maintain the dynamic stability of the shoulder joint. However, atrophy of the deltoid muscle may affect the stability of the shoulder joint, which in turn alters the mechanical distribution of rotator cuff tissue. Currently, the effect of muscle volume changes in the deltoid muscle on reducing the load on the rotator cuff tissue is still unknown. Therefore, this paper intends to analyze the mechanical changes of rotator cuff tissue by deltoid muscle atrophy through finite elements. Based on previously published finite element shoulder models, the deltoid muscle was modeled by constructing deltoid muscle models with different degrees of atrophy as, 100% deltoid muscle (Group 1), 80% deltoid muscle (Group 2), and 50% deltoid muscle (Group 3), respectively. The three models were given the same external load to simulate glenohumeral joint abduction, and the stress changes in the rotator cuff tissue were analyzed and recorded. In all three models, the stress in the rotator cuff tissue showed different degrees of increase with the increase of abduction angle, especially in the supraspinatus muscle. At 90° of glenohumeral abduction, supraspinatus stress increased by 58% and 118% in Group 2 and Group 3, respectively, compared with Group 1; In the subscapularis, the stress in Group 3 increased by 59% and 25% compared with Group 1 and Group 2, respectively. In addition, the stress of the infraspinatus muscle and teres minor muscle in Group 2 and Group 3 were higher than that in Group 1 during the abduction angle from 30° to 90°. Deltoid atrophy alters the abduction movement pattern of the glenohumeral joint. During glenohumeral abduction activity, deltoid atrophy significantly increases the stress on the rotator cuff tissue, whereas normal deltoid volume helps maintain the mechanical balance of the rotator cuff tissue.

Abstract Dysfunction of pancreatic δ cells contributes to the etiology of diabetes. Despite their important role, human δ cells are scarce, limiting physiological studies and drug discovery targeting δ cells. To date, no directed δ-cell differentiation method has been established. Here, we demonstrate that fibroblast growth factor (FGF) 7 promotes pancreatic endoderm/progenitor differentiation, whereas FGF2 biases cells towards the pancreatic δ-cell lineage via FGF receptor 1. We develop a differentiation method to generate δ cells from human stem cells by combining FGF2 with FGF7, which synergistically directs pancreatic lineage differentiation and modulates the expression of transcription factors and SST activators during endoderm/endocrine precursor induction. These δ cells display mature RNA profiles and fine secretory granules, secrete somatostatin in response to various stimuli, and suppress insulin secretion from in vitro co-cultured β cells and mouse β cells upon transplantation. The generation of human pancreatic δ cells from stem cells in vitro would provide an unprecedented cell source for drug discovery and cell transplantation studies in diabetes.

Abstract Background Renal cold ischemia-reperfusion injury (CIRI), a pathological process during kidney transplantation, may result in delayed graft function and negatively impact graft survival and function. There is a lack of an accurate and non-invasive tool for evaluating the degree of CIRI. Multi-parametric MRI has been widely used to detect and evaluate kidney injury. The machine learning algorithms introduced the opportunity to combine biomarkers from different MRI metrics into a single classifier. Objective To evaluate the performance of multi-parametric magnetic resonance imaging for grading renal injury in a rat model of renal cold ischemia-reperfusion injury using a machine learning approach. Methods Eighty male SD rats were selected to establish a renal cold ischemia -reperfusion model, and all performed multiparametric MRI scans (DWI, IVIM, DKI, BOLD, T1mapping and ASL), followed by pathological analysis. A total of 25 parameters of renal cortex and medulla were analyzed as features. The pathology scores were divided into 3 groups using K-means clustering method. Lasso regression was applied for the initial selecting of features. The optimal features and the best techniques for pathological grading were obtained. Multiple classifiers were used to construct models to evaluate the predictive value for pathology grading. Results All rats were categorized into mild, moderate, and severe injury group according the pathologic scores. The 8 features that correlated better with the pathologic classification were medullary and cortical Dp, cortical T2*, cortical Fp, medullary T2*, ∆T1, cortical RBF, medullary T1. The accuracy(0.83, 0.850, 0.81, respectively) and AUC (0.95, 0.93, 0.90, respectively) for pathologic classification of the logistic regression, SVM, and RF are significantly higher than other classifiers. For the logistic model and combining logistic, RF and SVM model of different techniques for pathology grading, the stable and perform are both well. Based on logistic regression, IVIM has the highest AUC (0.93) for pathological grading, followed by BOLD(0.90). Conclusion The multi-parametric MRI-based machine learning model could be valuable for noninvasive assessment of the degree of renal injury.

Abstract Background Radioresistance is the leading cause of death in advanced cervical cancer (CC). Dysregulation of RNA modification has recently emerged as a regulatory mechanism in radiation and drug resistance. We aimed to explore the biological function and clinical significance of 5-methylcytosine (m5C) in cervical cancer radiosensitivity. Methods The abundance of RNA modification in radiotherapy-resistant and sensitive CC specimens was quantified by liquid chromatography-tandem mass spectrometry. The essential RNA modification-related genes involved in CC radiosensitivity were screened via RNA sequencing. The effect of NSUN6 on radiosensitivity was verified in CC cell lines, cell-derived xenograft (CDX), and 3D bioprinted patient-derived organoid (PDO). The mechanisms of NSUN6 in regulating CC radiosensitivity were investigated by integrative m5C sequencing, mRNA sequencing, and RNA immunoprecipitation. Results We found a higher abundance of m5C modification in resistant CC samples, and NSUN6 was the essential m5C-regulating gene concerning radiosensitivity. NSUN6 overexpression was clinically correlated with radioresistance and poor prognosis in cervical cancer. Functionally, higher NSUN6 expression was associated with radioresistance in the 3D PDO model of cervical cancer. Moreover, silencing NSUN6 increased CC radiosensitivity in vivo and in vitro. Mechanistically, NDRG1 was one of the downstream target genes of NSUN6 identified by integrated m5C-seq, mRNA-seq, and functional validation. NSUN6 promoted the m5C modification of NDRG1 mRNA, and the m5C reader ALYREF bound explicitly to the m5C-labeled NDRG1 mRNA and enhanced NDRG1 mRNA stability. NDRG1 overexpression promoted homologous recombination-mediated DNA repair, which in turn led to radioresistance in cervical cancer. Conclusions Aberrant m5C hypermethylation and NSUN6 overexpression drive resistance to radiotherapy in cervical cancer. Elevated NSUN6 expression promotes radioresistance in cervical cancer by activating the NSUN6/ALYREF-m5C-NDRG1 pathway. The low expression of NSUN6 in cervical cancer indicates sensitivity to radiotherapy and a better prognosis.

In the Healthy China Strategy context, fish are increasingly in demand as a source of high-quality protein. Silver carp (Hypophthalmichthys molitrix) is a resource-rich and highly productive freshwater fish species found in China that is not edible raw or cooked in its original form due to its many boney spines. However, due to its advantages of being low-cost, low in fat, and high in protein, it is an ideal choice for surimi production. Currently, it is widely used in the industrial production of surimi products. The development of the freshwater surimi industry can significantly improve the added value of freshwater fish utilization, which has attracted extensive attention. Freshwater surimi is high in protein and low in fat and has a smooth and delicate taste, making it extremely popular with consumers. It has a high output, low price, is growing in demand, and is gradually being accepted throughout domestic and foreign markets. It has also driven the development of some related industries and produced significant economic and social benefits. As domestic consumers experience improved living standards and a faster pace of work, premade dishes containing surimi products as well as recreational snack surimi products with increased shelf-life are more attractive, as they save the consumer processing time, are enjoyed by the consumer, and meet their nutritional demands, affording these products great market potential. With the development of surimi products and related industries, specific requirements are being put forward for its production. Although China supplanted Japan as the largest producer of surimi products worldwide in 2006, ushering in a period of nearly 10 years of high production growth, the annual production of surimi products in China since 2014 has stagnated or even slightly decreased. Moreover, the surimi industry has entered a bottleneck period for quality enhancement caused by the expansion of quantity. The fishy odor of freshwater surimi is one of the industrial problems that affect the quality and efficiency of surimi. The flavor of surimi products (such as fish balls, fish intestines, fish cakes, and others in hot pot) has become one of the quality attributes that consumers are extremely concerned about. However, the adsorption and release laws of key odor-active substances are still unclear. There are existing research technologies for surimi odor, mainly including instrumental analysis (gas chromatography-mass spectrum, gas chromatography-olfactometry, gas chromatography-olfactometry- mass spectrum, electronic nose technology, etc.), sensomics analysis (odor activity value (OAV), aroma extract dilution analysis, odor recombination, odor omission test, etc.), and enzyme-linked immunosorbent assay. The research objects of odor sensory experiments are mostly rice wine, oil, vegetables, fruits, and fungi. Moreover, present odor research is mainly carried out in a prepared solution, mainly using odor recombination of a liquid simulation system, which is different from the interaction between the real odor active substance-solid surimi. Therefore, constructing an odor model based on solid surimi is necessary to better simulate the sensory characteristics of surimi. To build an odor model based on solid surimi, an odorless or low-odor surimi background model must be established in order to investigate the interaction between various odor components and surimi. There are several fishy substances and complex components in freshwater fish and surimi products, including aldehydes, alcohols, ketones, esters, sulfur compounds, nitrogen compounds, and alkanes.At present, most studies on rinsing surimi reported worldwide are based on how to better apply it to the food system, ignoring interactions between components in the complex system of surimi, which creates certain limitations in establishing a background model of surimi. Therefore, salt, salt-alcohol, acid, alkali, and other rinsing media were selected in this study, which was not limited to food systems. By comparing the removal effects of different rinsing media on the odor residue of surimi, an odorless or low-odor background model of surimi could be constructed. Here, the effect of different rinsing media on the odor residue of a surimi background model was studied. Specific rinsing media were as follows: 0.5% NaCl (W/W) + 0.35% Na2CO3 (W/W) + 4.0% C2H5OH (W/W) solution (group A), 0.5% NaCl (W/W) + 0.35% Na2CO3 solution (group B), 0.5% CaCl2 (W/W) + 0.35% Na2CO3 (W/W) + 4.0% C2H5OH (V/W) solution (group C), 0.5% CaCl2 (W/W) + 0.35% Na2CO3 (W/W) solution (group D), 1% NaCl (W/W) + 1% Na2CO3 (W/W) + 4.0% C2H5OH (V/W) solution (group E), 1% NaCl (W/W) + 1% Na2CO3 (W/W) solution (group F), 1 mol/L HCl solution (group G), and 1 mol/L NaOH solution (group H), respectively. The results showed that SPME-GC-MS detected 65 volatile compounds in silver carp surimi, including 22 aldehydes, 13 alcohols, 9 ketones, and 7 hydrocarbons, among which the contents of aldehydes and alcohols were high, which had a major contribution to the odor of silver carp surimi. A total of 18 odor-active substances were detected by the OAV (≥1) method, which helped illustrate that odor-active compounds contribute to the overall odor of surimi. After treatment with eight kinds of rinsing media, the residual amount of the odor-active substances in the silver carp surimi was washed or released to varying degrees, affecting the sample's overall odor contribution. The rinsed surimi samples contained 6,8,7,9,6,12,9, and 9 odor active compounds and residual rates of volatile odor compounds were (0.380±0.120)%, (0.610±0.086)%, (0.280±0.033)%, (0.480±0.037)%, (0.150±0.018)%, (4.330±0.160)%, (18.680±0.081)%, and (0.490±0.003)%, respectively. According to the SPME-GC-MS analysis results, due to the synergistic effect of ethanol, the content of volatile compounds detected in group E was the lowest, the total residual amount of odor-active compounds was reduced to (6.57±0.77) μg/kg, and the total residue rate was only 0.15%. Meanwhile, the total OAV decreased to 2.52±0.25, there were 17 odor-active substances with an OAV

Abstract The invasion of Mikania micrantha by climbing and covering trees has rapidly caused the death of many shrubs and trees, seriously endangering forest biodiversity. In this study, M. micrantha seedlings were planted together with local tree species (Cryptocarya concinna) to simulate the process of M. micrantha climbing under the forest. We found that the upper part of the M. micrantha stem lost its support after climbing to the top of the tree, grew in a turning and creeping manner, and then grew branches rapidly to cover the tree canopy. Then, we simulated the branching process through turning treatment. We found that a large number of branches had been formed near the turning part of the M. micrantha stem (TP). Compared with the upper part of the main stem (UP), the contents of plant hormones (auxin, cytokinin, gibberellin), soluble sugars (sucrose, glucose, fructose) and trehalose-6-phosphate (T6P) were significantly accumulated at TP. Further combining the transcriptome data of different parts of the main stem under erect or turning treatment, a hypothetical regulation model to illustrate how M. micrantha can quickly cover trees was proposed based on the regulation of sugars and hormones on plant branching; that is, the lack of support after ascending the top of the tree led to turning growth of the main stem, and the enhancement of sugars and T6P levels in the TP may first drive the release of nearby dormant buds. Plant hormone accumulation may regulate the entrance of buds into sustained growth and maintain the elongation of branches together with sugars to successfully covering trees.

Abstract Background Poly (ADP-ribose) polymerase inhibitor (PARPi) resistance poses a significant challenge in ovarian carcinoma (OC). While the role of DOT1L in cancer and chemoresistance is acknowledged, its specific role in PARPi resistance remains unclear. This study aims to elucidate the molecular mechanism of DOT1L in PARPi resistance in OC patients. Methods This study analyzed the expression of DOT1L in PARPi-resistant cell lines compared to sensitive ones and correlated it with clinical outcomes in OC patients. Comprehensive in vitro and in vivo functional experiments were conducted using cellular and mouse models. Molecular investigations, including RNA sequencing, chromatin immunoprecipitation (ChIP) and Cleavage Under Targets and Tagmentation (CUT&Tag) assays, were employed to unravel the molecular mechanisms of DOT1L-mediated PARPi resistance. Results Our investigation revealed a robust correlation between DOT1L expression and clinical PARPi resistance in non-BRCA mutated OC cells. Upregulated DOT1L expression in PARPi-resistant tissues was associated with diminished survival in OC patients. Mechanistically, we identified that PARP1 directly binds to the DOT1L gene promoter, promoting transcription independently of its enzyme activity. PARP1 trapping induced by PARPi treatment amplified this binding, enhancing DOT1L transcription and contributing to drug resistance. Sequencing analysis revealed that DOT1L plays a crucial role in the transcriptional regulation of PLCG2 and ABCB1 via H3K79me2. This established the PARP1-DOT1L-PLCG2/ABCB1 axis as a key contributor to PARPi resistance. Furthermore, we discovered that combining a DOT1L inhibitor with PARPi demonstrated a synergistic effect in both cell line-derived xenograft mouse models (CDXs) and patient-derived organoids (PDOs). Conclusions Our results demonstrate that DOT1L is an independent prognostic marker for OC patients. The PARP1-DOT1L/H3K79me2-PLCG2/ABCB1 axis is identified as a pivotal contributor to PARPi resistance. Targeted inhibition of DOT1L emerges as a promising therapeutic strategy for enhancing PARPi treatment outcomes in OC patients.

Abstract Circadian rhythms are present in almost all cells and play a crucial role in regulating various biological processes. Maintaining a stable circadian rhythm is essential for overall health. Disruption of this rhythm can alter the expression of clock genes and cancer-related genes, and affect many metabolic pathways and factors, thereby affecting the function of the immune system and contributing to the occurrence and progression of tumors. This paper aims to elucidate the regulatory effects of BMAL1, clock and other clock genes on immune cells, and reveal the molecular mechanism of circadian rhythm’s involvement in tumor and its microenvironment regulation. A deeper understanding of circadian rhythms has the potential to provide new strategies for the treatment of cancer and other immune-related diseases.

Abstract Background Breast cancer is the most common cancer in women worldwide. Toxoplasma gondii (T. gondii) has shown anticancer activity in breast cancer mouse models, and exerted beneficial effect on the survival of breast cancer patients, but the mechanism was unclear. Methods The effect of tachyzoites of T. gondii (RH and ME49 strains) on human breast cancer cells (MCF-7 and MDA-MB-231 cells) proliferation and migration was assessed using cell growth curve and wound healing assays. Dual RNA-seq was performed for T. gondii-infected and non-infected cells to determine the differentially expressed genes (DEGs). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein–Protein Interaction Networks analysis (PPI) were performed to explore the related signaling pathway and hub genes. Hub genes were validated using the Kaplan–Meier plotter database, and Pathogen Host Interaction (PHI-base) database. The results were verified by qRT-PCR. Results The tachyzoites of T. gondii decreased the expression of Ki67 and increased the expression of E-cadherin, resulting in suppressing the proliferation and migration of infected human breast cancer cells. The inhibitory effect of T. gondii on breast cancer cells showed a significant dose–response relationship. Compared with the control group, 2321 genes were transcriptionally regulated in MCF-7 cells infected with T. gondii, while 169 genes were transcriptionally regulated in infected MDA-MB-231 cells. Among these genes, 698 genes in infected MCF-7 cells and 67 genes in infected MDA-MB-231 cells were validated by the publicly available database. GO and KEGG analyses suggested that several pathways were involved in anticancer function of T. gondii, such as ribosome, interleukin-17 signaling, coronavirus disease pathway, and breast cancer pathway. BRCA1, MYC and IL-6 were identified as the top three hub genes in infected-breast cancer cells based on the connectivity of PPI analysis. In addition, after interacting with breast cancer cells, the expression of ROP16 and ROP18 in T. gondii increased, while the expression of crt, TgIST, GRA15, GRA24 and MIC13 decreased. Conclusions T. gondii transcriptionally regulates several signaling pathways by altering the hub genes such as BRCA1, MYC and IL-6, which can inhibit the breast tumor growth and migration, hinting at a potential therapeutic strategy.

Abstract The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in β cells. This upregulation increases both insulin secretion and susceptibility of β cells to SARS-CoV-2 infection. Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation, subsequently reducing viral infection and replication in the islets. Furthermore, retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms. Finally, animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels, resulting in a reduction of insulin concentrations in situ. Taken together, our research offers a potential regulatory strategy for ACE2 by controlling FGF7, thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.

To investigate the effect of poly-γ-glutamic acid (γ-PGA) biopreparation on ameliorating coastal saline soil, three treatments were established: soil salt washed treatment (CK), soil salt washed with added γ-PGA (PGA), soil salt washed with added γ-PGA biopreparation (PGAB). This study determined the effects of γ-PGA on coastal saline soil by analyzing soil aggregate, soil evaporation, soil vertical water and salt distribution, and soil cation content, soil pH, soil nutrient content and soil microorganism quantity. Results showed that γ-PGA had an ameliorative effect on saline soil, with the PGAB treatment exhibiting the most pronounced ameliorative effect compared to CK. Adding PGAB reduced soil evaporation by 30.45 %, soil salt content by 27.91 %, meanwhile increasing plant height by 33.86 %, plant fresh weight by 98.54 %, soil aggregate diameter by 6.68 times, soil water content by 26.47 % (P

Understanding the relationship between sediment loading and its environmental implications in river systems is crucial for water resource management and environmental protection. This study explored the spatiotemporal characteristics of sediment loading and their environmental relationships in seven large rivers in China, aiming to quantify the contributions of various factors to changes in sediment transport. Monitoring data spanning twenty-one years (2002 to 2022) on sediments, hydrology, and the environment collected by sixty-five stations were analysed. The multivariate statistical techniques employed included Spearman’s correlation analysis, principal component analysis, and multivariate regression modeling. The results show that sediment transport in various river systems exhibited spatial heterogeneity, the maximum annual average sediment loadings (1.59 × 108 t/yr) occur in the lower reaches of the Yellow River, the middle reaches have the highest sediment concentration (41.54 kg/m3), followed by the downstream of the Yellow River (5.85 kg/m3). Sediment loading and runoff changes in the basins did not adhere universally to synchronous patterns. Eleven of the thirteen basins of these river systems showed upward trends in annual runoff volume, whereas nine basins showed downward trends in annual sediment loading. Runoff volume accounted for over 30 % explanatory of sediment loading variations in all seven large river systems, with the Yangtze, Huaihe, Qiantang, and Songhua rivers surpassing 60 % of the explanatory power. The Normalized Difference Vegetation Index of all watersheds showed an increasing trend, whereas the index of nine of the thirteen watersheds was correlated negatively with sediment transport. The influence of human activities on basin sediment transport was higher than that of natural resilience, whereas afforestation significantly reduced sediment in arid regions. This study provides insight into the temporal and spatial characteristics of sediment loadings and the driving effects of environmental factors, which has great significance for watershed environmental management.

BackgroundIn recent years, the number of artificial cervical disc replacements has increased, and paravertebral ectopic ossification is a common complication. Although the exact mechanism is not clear, some studies suggest that it is related to the concentration of tissue stress caused by incomplete coverage of the trailing edge of the endplate. Therefore, this study performed a quantitative analysis to compare the biomechanical effects of different sagittal distances at the posterior edge of the endplate of the upper and lower prosthesis on the cervical spine and to explore the mechanical response of incomplete coverage of the posterior edge of the endplate on the paravertebral tissues.MethodsA C2-C7 nonlinear finite element model of the cervical spine was established and validated. Based on the cervical spine model, cervical disc replacement surgery models were constructed with different distances of sagittal distance at the posterior edge of the upper prosthetic endplate (0, 1, 2, 3 mm, respectively) and sagittal distance at the posterior edge of the lower prosthetic endplate (1, 2, 3 mm, respectively). Each model was subjected to the same 1Nm torque and 73.6N driven compressive load. Range of motion (ROM), intervertebral disc pressure (IDP), facet joint force (FJF), and endplate stress were measured at the cervical surgical and other segments.ResultsCompared to the intact cervical spine model, the sagittal distance of the posterior edge of the prosthesis endplate at different distances increased the stress on the intervertebral disc and the capsular joint in the adjacent vertebral body segments to different degrees, especially in extension. In different directions of motion, the posterior margin sagittal distance of the posterior edge of the endplate of the lower prosthesis has a greater mechanical influence on the cervical spine compared to the posterior margin sagittal distance of the posterior edge of the endplate of the upper prosthesis. Compared with the intact model, the biomechanical parameters (ROM, FJF, endplate stress) of the C5-C6 segment increased the most when the sagittal distance of the posterior edge of the endplate of the upper prosthesis was 3 mm. Compared with the intact model, the maximum intervertebral disc stress of C4-C5 and C6-C7 was 0.57 MPa and 0.53 MPa, respectively, when the sagittal distance of the posterior edge of the upper prosthetic endplate was 3 mm.ConclusionAfter the sagittal distance of the posterior edge of the prosthetic endplate was completely covered, the mechanical influence of the entire cervical spine was low. The sagittal distance at the posterior edge of the endplate of different sizes changed the motion pattern and load distribution of the implanted segment to some extent. When the sagittal distance between the prosthesis and the upper endplate was greater than or equal to 3 mm, the mechanical indices of the implanted segment increased significantly, increasing the risk of local tissue injury, especially during extension motion. Compared to the sagittal distance at the posterior edge of the endplate of the lower prosthesis, increasing the sagittal distance at the posterior edge of the endplate of the upper prosthesis has a greater effect on the mechanics of the cervical spine.

PurposeTo explore the consistency of FRACTURE (Fast-field-echo Resembling A CT Using Restricted Echo-spacing) MRI and X-Ray/computerized tomography (CT) in the evaluation of bone injuries in knee and ankle joints.MethodsFrom Nov. 2020 to Jul. 2023, 42 patients with knee joint or ankle joint injuries who underwent FRACTURE MRI examinations were retrospectively collected. 11 patients were examined by both X-Ray and FRACTURE examinations. 31 patients were examined by both CT and FRACTURE examinations. The fracture, osteophyte, and bone destruction of the joints were evaluated by two radiologists using X-Ray/CT and FRACTURE images, respectively. Kappa test was used for consistency analysis.ResultsThe evaluation consistency of fracture, osteophyte and bone destruction via X-Ray and FRACTURE images by radiologist 1 were 0.879, 0.867 and 0.847 respectively, and for radiologist 2 were 0.899, 0.930, and 0.879, respectively. The evaluation consistency of fracture, osteophyte and bone destruction via CT and FRACTURE images by radiologist 1 were 0.938, 0.937 and 0.868 respectively, and for radiologist 2 were 0.961, 0.930, and 0.818, respectively.ConclusionFor fracture, osteophyte, and bone destruction of knee and ankle joints. FRACTURE MRI showed a high consistency with X-Ray/CT examinations.

Histoplasmosis is a systemic mycosis caused by the dimorphic fungus in the genus Histoplasma. Histoplasmosis is overlooked in China. This study aims to provide an epidemiological and clinical update on histoplasmosis in China by literature review. We reviewed cases of histoplasmosis reported in recent 11 years and described a case of histoplasmosis-triggered hemophagocytic lymphohistiocytosis (HLH) in an immunocompetent patient. A total of 225 cases of histoplasmosis diagnosed in China between 2012 and 2022 were involved in this study, compared with 300 cases reviewed from 1990 to 2011, an increasing number of cases of histoplasmosis have been diagnosed in the last 11 years. The majority of cases of histoplasmosis were autochthonous cases, mainly from provinces Sichuan (56/225, 24.9%), Hunan (50/225, 22.2%), Guangdong (31/225, 13.8%), and Yunnan (24/225, 10.7%). Higher incidence (52.5%, 53/99) of histoplasmosis occurred in immunocompetent patients which is similar to those from the previous 21 years, and the prevalence of the disease did not vary highly over time. Of note, the number of histoplasmosis cases is increasing, and the geographic distribution is shifting southwards over time. Improved awareness is critically important for informing clinical practice in China.

Chlorophyll-a (Chl-a) and algal cell density (ACD) are vital for assessing algal proliferation and eutrophication in aquatic ecosystems. Although Chl-a is often used as a proxy for ACD, its accuracy requires validation, and studies on their linear correlation are scarce. Additionally, Chl-a and ACD are influenced by various factors, including nutritional, economic, biochemical, physicochemical, and meteorological factors. However, the relative importance of these factors on Chl-a and ACD remains insufficiently studied. This study analyzed data from 57 lakes and reservoirs across China from March 2021 to February 2023, investigating the distribution patterns of Chl-a and ACD across different regions and seasons. The study employed a linear regression model to explore the correlation between Chl-a and ACD in various regions and seasons throughout China. Furthermore, Mantel test and generalized linear model were used to evaluated the relative importance of nutritional factors (total nitrogen (TN), total phosphorus (TP), TN/TP ratio (TN/TP), and ammonia nitrogen (NH3-N)), economic factors (gross domestic product), meteorological factors (surface pressure, net solar radiation, air temperature, wind speed (WS), and rainfall (RF)), as well as biochemical and physicochemical factors (turbidity (TUR), pH value, water temperature (WT), permanganate index, and dissolved oxygen) on Chl-a and ACD. Results showed that the average concentrations of Chl-a and ACD in South China were highest, at 12 μg/L and 19.5 × 106 cells/L, respectively. Seasonally, Chl-a peaked in spring and was lowest in winter, while ACD peaked in summer and was lowest in winter. Significant seasonal and regional variations in the Chl-a and ACD correlation were observed, with spring showing the strongest relationship. In Central China, Chl-a and ACD were significantly correlated throughout the four seasons, whereas correlations were less distinct in Eastern and Western regions. Therefore, Chl-a as a proxy for ACD requires caution. Nutrient factors (TN, TP, TN/TP, NH3-N) were identified as the primary drivers of Chl-a and ACD. Meteorological factors (WS, RF), along with biochemical and physicochemical factors (WT, TUR) also emerged as critical predictors of Chl-a and ACD, with spatial variations. This study validates Chl-a as a proxy for ACD, analyzes their spatiotemporal distribution, and assesses the influence of various factors on Chl-a and ACD, enhancing our understanding of algal dynamics in Chinese lakes and reservoirs.

The value of Baijiu is affected by its flavor, age, and adulteration. Therefore, a simple and rapid identification method is crucial for the market. In this study, we present a rapid, non-intrusive identification technique for Baijiu utilizing the Tyndall effect combined with chemometrics analysis. Our experiment begins illuminating Baijiu with a 405 nm wavelength laser and recording the resulting bright light path due to the Tyndall effect. To further analyze the color and brightness information, Principal Component Analysis (PCA), Linear Discriminant Analysis (LDA), Hierarchical Cluster Analysis (HCA), and Multilayer Perceptron (MLP) were employed. This study establishes correlations between the brightness of the Tyndall light path and seven trace flavor compounds in Baijiu. The findings demonstrate that this method effectively identifies the flavor, age cellar, and adulteration of Baijiu and also quantitatively detects the concentrations of flavor compounds. Additionally, an analysis platform was developed to enable the rapid identification of Baijiu.

Somatostatin (SST)-producing pancreatic delta-cells play an important role in maintaining the balance of insulin and glucagon secretion within the islets. This study aimed to generate a human embryonic stem cell (hESC) line with a SST-P2A-mCherry reporter using CRISPR/Cas9 system. The SST-P2A-mCherry reporter cell line was shown to maintain typical pluripotent characteristics and able to be induced into SST-producing pancreatic delta-cells. The generation of the cell line would provide useful platform for the characterization of stem cell-derived delta-cells, discovery of delta-cell surface markers and investigation of paracrine mechanisms, which will ultimately promote the drug discovery and cell therapy of diabetes mellitus.

BackgroundThis study aimed to explore the knowledge and attitude (KA) toward postoperative antithrombotic management and prevention among coronary artery disease (CAD) patients who underwent coronary revascularization.MethodsThis cross-sectional study enrolled CAD outpatients and inpatients between May and December 2023 at Kailuan Medical Group at Tangshan. Basic demographic characteristics and KA scores were collected through a self-made questionnaire.ResultsThis study included 523 valid questionnaires. The mean knowledge and attitude scores were 13.20 ± 6.20 (range: 0–26) and 43.68 ± 6.01 (range: 21–50), respectively, indicating poor knowledge and favorable attitude. Multivariable logistic regression analysis showed that junior high school education (OR = 2.160, P = 0.035), high school or technical school education (OR = 2.356, P = 0.039), and monthly average income >5,000 RMB (OR = 3.407, P = 0.002) were independently associated with knowledge. Knowledge (OR = 1.095, P = 0.002), BMI ≥ 24.0 kg/m2 (OR = 0.372, P = 0.011), junior high school (OR = 3.699, P = 0.002), high school or technical school (OR = 2.903, P = 0.028), high associate degree or above education (OR = 6.068, P = 0.014), monthly average income 3,000–5,000 RMB (OR = 0.296, P = 0.005), monthly average income > 5,000 RMB (OR = 0.225, P = 0.021), with hypertension (OR = 0.333, P = 0.003), blood tests every 2–3 weeks (OR = 10.811, P = 0.011), blood tests every month (OR = 4.221, P = 0.024), and blood tests every 2–3 months (OR = 3.342, P = 0.033) were independently associated with attitude.ConclusionCAD patients who underwent coronary revascularization had poor knowledge but favorable attitudes toward postoperative antithrombotic management and prevention. The study underscores the need for targeted education, especially for individuals with lower education and income levels, ultimately improving patient compliance and cardiovascular outcomes.

BackgroundThe interaction between environmental endocrine-disrupting chemicals, such as Bisphenol A (BPA), and their influence on cancer progression, particularly regarding the GOLPH3 gene in colorectal cancer, remains unclear.MethodsWe performed an integrated analysis of transcriptional profiling, clinical data, and bioinformatics analyses utilizing data from the Comparative Toxicogenomics Database and The Cancer Genome Atlas. The study employed ClueGO, Gene Set Enrichment Analysis, and Gene Set Variation Analysis for functional enrichment analysis, alongside experimental assays to examine the effects of BPA exposure on colorectal cancer cell lines, focusing on GOLPH3 expression and its implications for cancer progression.ResultsOur findings demonstrated that BPA exposure significantly promoted the progression of colorectal cancer by upregulating GOLPH3, which in turn enhanced the malignant phenotype of colorectal cancer cells. Comparative analysis revealed elevated GOLPH3 protein levels in cancerous tissues versus normal tissues, with single-cell analysis indicating widespread GOLPH3 presence across various cell types in the cancer microenvironment. GOLPH3 was also associated with multiple carcinogenic pathways, including the G2M checkpoint. Furthermore, our investigation into the colorectal cancer microenvironment and genomic mutation signature underscored the oncogenic potential of GOLPH3, exacerbated by BPA exposure.ConclusionThis study provides novel insights into the complex interactions between BPA exposure and GOLPH3 in the context of colorectal cancer, emphasizing the need for heightened awareness and measures to mitigate BPA exposure risks. Our findings advocate for further research to validate these observations in clinical and epidemiological settings and explore potential therapeutic targets within these pathways.

IntroductionTo investigate the prognostic value of the consistency between the residual quantitative flow ratio (QFR) and postpercutaneous coronary intervention (PCI) QFR in patients undergoing revascularization.MethodsThis was a single-center, retrospective, observational study. All enrolled patients were divided into five groups according to the ΔQFR (defined as the value of the post-PCI QFR minus the residual QFR): (1) Overanticipated group; (2) Slightly overanticipated group; (3) Consistent group; (4) Slightly underanticipated group; and (5) Underanticipated group. The primary outcome was the 5-year target vessel failure (TVF).ResultsA total of 1373 patients were included in the final analysis. The pre-PCI QFR and post-PCI QFR were significantly different among the five groups. TVF within 5 years occurred in 189 patients in all the groups. The incidence of TVF was significantly greater in the underanticipated group than in the consistent group (P = 0.008), whereas no significant differences were found when comparing the underanticipated group with the other three groups. Restricted cubic spline regression analysis showed that the risk of TVF was nonlinearly related to the ΔQFR. A multivariate Cox regression model revealed that a ΔQFR≤ −0.1 was an independent risk factor for TVF.ConclusionsThe consistency between the residual QFR and post-PCI QFR may be associated with the long-term prognosis of patients. Patients whose post-PCI QFR is significantly lower than the residual QFR may be at greater risk of TVF. An aggressive PCI strategy for lesions is anticipated to have less functional benefit and may not result in a better clinical outcome.

Abstract Hepatocellular carcinoma (HCC) is a form of malignancy with limited curative options available. To improve therapeutic outcomes, it is imperative to develop novel, potent therapeutic modalities. Ketoconazole (KET) has shown excellent therapeutic efficacy against HCC by eliciting apoptosis. However, its limited water solubility hampers its application in clinical treatment. Herein, a mitochondria‐targeted chemo‐photodynamic nanoplatform, CS@KET/P780 NPs, is designed using a nanoprecipitation strategy by integrating a newly synthesized mitochondria‐targeted photosensitizer (P780) and chemotherapeutic agent KET coated with chondroitin sulfate (CS) to amplify HCC therapy. In this nanoplatform, CS confers tumor‐targeted and subsequently pH‐responsive drug delivery behavior by binding to glycoprotein CD44, leading to the release of P780 and KET. Mechanistically, following laser irradiation, P780 targets and destroys mitochondrial integrity, thus inducing apoptosis through the enhancement of reactive oxygen species (ROS) buildup. Meanwhile, KET‐induced apoptosis synergistically enhances the anticancer effect of P780. In addition, tumor cells undergoing apoptosis can trigger immunogenic cell death (ICD) and a longer‐term antitumor response by releasing tumor‐associated antigens (TAAs) and damage‐associated molecular patterns (DAMPs), which together contribute to improved therapeutic outcomes in HCC. Taken together, CS@KET/P780 NPs improve the bioavailability of KET and exhibit excellent therapeutic efficacy against HCC by exerting chemophototherapy and antitumor immunity.

Objective: To evaluate and compare the image quality of T2-weighted abdominal scans using a respiratory belt trigger (RBT) and frequency-modulated continuous wave (FMCW)-trigger (FT) techniques and to explore the feasibility of FT in abdominal magnetic resonance imaging (MRI).Methods: The study prospectively included 28 subjects, each undergoing abdominal scans with both RBT and FT. The analysis focused on 64 inconsistent trigger segments from the respiratory curves triggered by RBT and FMCW. Parameters such as inconsistent trigger type (ITT), number of inconsistent trigger points (ITPs), ratio of ITP (ITR), and single-segment ITR (SITR) were derived from these curves. Image quality was evaluated by two observers using subjective scoring, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). The assessments classified image quality as either “good” or “poor.” Consistency in image quality assessment between observers was determined using the kappa test and intraclass correlation coefficient (ICC). The chi-square test, Student’s t-test, and the Mann–Whitney U test were employed to compare the categorical and continuous variables between the RBT and FT groups.Results: The observers showed a high level of agreement in image quality assessment. There were no significant differences in ITR, SITR, acquisition time, SNR, and CNR between the RBT and FT groups (all p > 0.05). Both subjective and objective evaluations indicated no notable difference in image quality between the two groups (p > 0.05).Conclusion: The FMCW trigger technique is a viable alternative to the traditional respiratory belt trigger in scenarios of relatively stable breathing. It offers potential benefits, such as reducing operational demands on technicians and improving MRI workflow efficiency.

Abstract Background The prognostic significance of non‐cancer‐related prognostic factors, such as body composition, has gained extensive attention in oncological research. Compared with sarcopenia, the prognostic significance of adipose tissue for overall survival in non‐small cell lung cancer remains unclear. We investigated the prognostic value of skeletal muscle and adipose tissue in patients with non‐small cell lung cancer. Methods This retrospective study included 4434 patients diagnosed with non‐small cell lung cancer between January 2014 and December 2016. Cross‐sectional areas of skeletal muscle and subcutaneous fat were measured, and the pericardial fat volume was automatically calculated. The skeletal muscle index and subcutaneous fat index were calculated as skeletal muscle area and subcutaneous fat area divided by height squared, respectively, and the pericardial fat index was calculated as pericardial fat volume divided by body surface area. The association between body composition and outcomes was evaluated using Cox proportional hazards model. Results A total of 750 patients (501 males [66.8%] and 249 females [33.2%]; mean age, 60.9 ± 9.8 years) were included. Sarcopenia (60.8% vs. 52.7%; P 0.05). Conclusions Increased subcutaneous fat index and pericardial fat index were associated with a higher 5‐year overall survival rate, independent of sarcopenia, in non‐small cell lung cancer and may indicate a reduced risk of non‐cancer‐related death.

Insulin secretion by pancreatic islets plays a vital role in regulating blood glucose levels. Nevertheless, the mechanism responsible for this dynamic insulin secretion has not been completely understood, particularly at the single islet level. In this study, we have successfully developed an easy microfluidic platform that allows for the exploration of dynamic glucose-stimulated insulin secretion (GSIS) at the single islet level. With the utilization of this platform, we evaluated dynamic GSIS from single islets isolated from both normal and diabetic rats. Our results demonstrate that islets can be categorized into three types based on their dynamic GSIS: Type I exhibits a biphasic GSIS profile with a fast first phase and flat second phase; Type II also has a biphasic GSIS profile with a fast first phase but a slow increased second phase; Type III displays only a slowly increased second phase and lacks a fast first phase. RNA sequencing analysis demonstrated that the cell type and exocytosis-specific genes are consistent with the proportion of cells and insulin release kinetics among the three types of islets, respectively. Moreover, our findings suggest that high expression of Atp5pb is anti-correlated with the first phase of insulin secretion. Furthermore, we revealed that diabetic islets exhibit only the type I GSIS response, indicating a deliberate impairment of the second phase of insulin secretion. Together, this device serves as a crucial tool in the research field of islets and diabetes, allowing researchers to investigate islet functional heterogeneity and identity at the single islet level.

Abstract Background Noninvasive and precise methods to estimate treatment response and identify hepatocellular carcinoma (HCC) patients who could benefit from transarterial chemoembolization (TACE) are urgently required. The present study aimed to investigate the ability of intratumoral and peritumoral radiomics based on contrast-enhanced magnetic resonance imaging (CE-MRI) to preoperatively predict tumor response to TACE in HCC patients. Methods A total of 138 patients with HCC who received TACE were retrospectively included and randomly divided into training and validation cohorts at a ratio of 7:3. Total 1206 radiomics features were extracted from arterial, venous, and delayed phases images. The inter- and intraclass correlation coefficients, the spearman’s rank correlation test, and the gradient boosting decision tree algorithm were used for radiomics feature selection. Radiomics models on intratumoral region (TR) and peritumoral region (PTR) (3 mm, 5 mm, and 10 mm) were established using logistic regression. Three integrated radiomics models, including intratumoral and peritumoral region (T-PTR) (3 mm), T-PTR (5 mm), and T-PTR (10 mm) models, were constructed using TR and PTR radiomics scores. A clinical-radiological model and a combined model incorporating the optimal radiomics score and selected clinical-radiological predictors were constructed, and the combined model was presented as a nomogram. The discrimination, calibration, and clinical utilities were evaluated by receiver operating characteristic curve, calibration curve, and decision curve analysis, respectively. Results The T-PTR radiomics models performed better than the TR and PTR models, and the T-PTR (3 mm) radiomics model demonstrated preferable performance with the AUCs of 0.884 (95%CI, 0.821–0.936) and 0.911 (95%CI, 0.825–0.975) in both training and validation cohorts. The T-PTR (3 mm) radiomics score, alkaline phosphatase, tumor size, and satellite nodule were fused to construct a combined nomogram. The combined nomogram [AUC: 0.910 (95%CI, 0.854–0.958) and 0.918 (95%CI, 0.831–0.986)] outperformed the clinical-radiological model [AUC: 0.789 (95%CI, 0.709–0.863) and 0.782 (95%CI, 0.660–0.902)] in the both cohorts and achieved good calibration capability and clinical utility. Conclusions CE-MRI-based intratumoral and peritumoral radiomics approach can provide an effective tool for the precise and individualized estimation of treatment response for HCC patients treated with TACE.

Infection with the Hantaan virus (HTNV) may result in severe hemorrhagic fever with renal syndrome (HFRS). The functions of HLA-E-restricted CD8+ T lymphocytes in virus control and vaccine development have recently received increased attention. The purpose of this research is to discover HLA-E-restricted CD8+ T cell epitopes on HTNV as well as the features of these epitope-specific CD8+ T cells in HFRS patients. To anticipate HLA-E-restricted HTNV epitopes, the NetMHCpan servers were utilized. The K562/HLA-E cell binding test and the enzyme-linked immunospot assay were used to confirm epitope binding to HLA-E. The number and features of HLA-E-restricted epitope-specific CD8+ T lymphocytes in HFRS patients were investigated using tetramer staining, intracellular cytokine labeling, proliferation, and cytotoxicity assays. Six HTNV-derived HLA-E-restricted CD8+ T cell epitopes were found in this study. In mild/moderate HFRS patients, the frequency of HLA-E-restricted epitope-specific CD8+ T cells was greater than in severe/critical patients. CD38+HLA-DR+ HLA-E-restricted CD8+ T cells were identified. Meanwhile, CD45RA+CCR7− effector memory-re-expressing CD45RA T cells with early and intermediate maturation and differentiation characteristics predominated. Notably, CD8+ T cells from milder HFRS patients produced more interferon-γ, interleukin-2, and granzyme B, had a stronger proliferative potential, and were inversely linked with the amount of plasma HTNV virus load. Furthermore, HLA-E-restricted epitope-specific CD8+ T cells demonstrated improved cytotoxic activity in vitro during the acute stage of HFRS. Taken together, the findings demonstrate the protective effects of HLA-E-restricted CD8+ T cells during HTNV infection, suggesting that HLA-E-targeted vaccines against HTNV might be developed for HLA-diverse populations.

Converting carbon dioxide (CO2) into high-value-added chemicals using solar energy is a promising approach to reducing carbon dioxide emissions; however, single photocatalysts suffer from quick the recombination of photogenerated electron–hole pairs and poor photoredox ability. Herein, silver (Ag) nanoparticles featuring with localized surface plasmon resonance (LSPR) are combined with g-C3N4 to form a Schottky junction for photothermal catalytic CO2 reduction. The Ag/g-C3N4 exhibits higher photocatalytic CO2 reduction activity under UV-vis light; the CH4 and CO evolution rates are 10.44 and 88.79 µmol·h−1·g−1, respectively. Enhanced photocatalytic CO2 reduction performances are attributed to efficient hot electron transfer in the Ag/g-C3N4 Schottky junction. LSPR-induced hot electrons from Ag nanoparticles improve the local reaction temperature and promote the separation and transfer of photogenerated electron–hole pairs. The charge carrier transfer route was investigated by in situ irradiated X-ray photoelectron spectroscopy (XPS). The three-dimensional finite-difference time-domain (3D-FDTD) method verified the strong electromagnetic field at the interface between Ag and g-C3N4. The photothermal catalytic CO2 reduction pathway of Ag/g-C3N4 was investigated using in situ diffuse reflectance infrared Fourier transform spectra (DRIFTS). This study examines hot electron transfer in the Ag/g-C3N4 Schottky junction and provides a feasible way to design a plasmonic metal/polymer semiconductor Schottky junction for photothermal catalytic CO2 reduction.

Abstract Microgravity is one of the most common causes counting for the bone loss. Mesenchymal stem cells (MSCs) contribute greatly to the differentiation and function of bone related cells. The development of novel MSCs biomarkers is critical for implementing effective therapies for microgravity induced bone loss. We aimed to find the new molecules involved in the differentiation and function of MSCs in mouse simulated microgravity model. We found CD226 was preferentially expressed on a subset of MSCs. Simulation of microgravity treatment significantly increased the proportion of CD226+Lin−CD117−Sca1+ MSCs. The CD226+ MSCs produced higher IL‐6, M‐CSF, RANKL and lower CD200 expression, and promoted osteoclast differentiation. This study provides pivotal information to understand the role of CD226 in MSCs, and inspires new ideas for prevention of bone loss related diseases.

Gestational diabetes mellitus (GDM) is a gestational disorder characterized by hyperglycemia, that can lead to dysfunction of diverse cells in the body, especially the immune cells. It has been reported that immune cells, specifically natural killer (NK) cells, play a crucial role in normal pregnancy. However, it remains unknown how hyperglycemia affects NK cell dysfunction thus participates in the development of GDM. In this experiment, GDM mice were induced by an intraperitoneal injection of streptozotocin (STZ) after pregnancy and it has been found that the intrauterine growth restriction occurred in mice with STZ-induced GDM, accompanied by the changed proportion and function of NK cells. The percentage of cytotoxic CD27-CD11b+ NK cells was significantly increased, while the proportion of nourished CD27-CD11b- NK cells was significantly reduced in the decidua of GDM mice. Likewise, the same trend appeared in the peripheral blood NK cell subsets of GDM patients. What’s more, after intrauterine reinfusion of NK cells to GDM mice, the fetal growth restriction was alleviated and the proportion of NK cells was restored. Our findings provide a theoretical and experimental basis for further exploring the pathogenesis of GDM.

Concrete reinforcement is essential for ensuring the safety and durability of concrete structures. Bonding steel plates to reinforce concrete is widely used to renovate or strengthen concrete beam structures. Due to construction quality and the influence of factors such as environment and fatigue, debonding often occurs between the steel plate and concrete, making monitoring and early warning after concrete structure reinforcement challenging. This paper proposes a novel approach to monitor the degree of debonding between the steel plate and concrete beam using active sensing technology. The method uses lead zirconate titanate (PZT) as an actuator to generate stress waves. It prepares strip sensors with polyvinylidene fluoride as the sensing element to monitor stress waves passing through the steel plate and concrete beam. The monitoring system detects the degree of debonding between the steel plate and the concrete beam by monitoring the change in surface voltage of the sensor. Experiments show that the degree of debonding significantly correlates with the received voltage signal; the higher the debonding, the larger the received voltage signal. It is also observed that, at the same degree of debonding, the actuator and sensor attachment position have a particular impact on the received voltage signal. Through experiments and numerical simulation analysis, it is found that when the sensor is attached to the left side of the steel plate, that is, the bonded section of the steel plate, the amplitude of the voltage signal collected by the dynamic information acquisition system is the smallest, i.e., V_debonded section > V_middle > V_bonded section. Based on the above research, the active sensing technology proposed in this paper has good sensitivity to the degree of debonding between the steel plate and concrete. It is expected to become an effective monitoring and evaluation method for the degree of debonding between steel plates and concrete.

The study aimed to estimate the feasibility of α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), and γ-cyclodextrin (γ-CD) to encapsulate Mosla chinensis essential oil (EO) by ultrasonic-assisted method. The physical properties variations, stabilization mechanisms, and formation processes of the inclusion complexes (ICs) were investigated using experimental methods, molecular docking, and molecular dynamics (MD) simulation. Scanning electron microscopy, fourier transform infrared spectroscopy, thermogravimetric analysis, and gas chromatography–mass spectrometry showed that the ICs were successfully prepared, which differentially improved the thermal stability and retained the chemical composition of EO. The dissolution profile showed that the Peppas model can be used to describe the diffuse release mechanism of EO. Finally, molecular docking and MD simulation theoretically confirmed the interaction and conformational changes of carvacrol (the main active component of Mosla chinensis EO) inside the cavity of CDs. The results indicate that hydrogen bonding was the primary driving force for the carvacrol spontaneous access to the cavity. Further, a binding dynamic balance occurs between carvacrol and β-CD, whereas a bind and away dynamic balance occurs in the IC between carvacrol and α-CD, γ-CD. The comprehensive results show that the medium cavity size of β-CD is a suitable host molecule for Mosla chinensis EO of encapsulation, release, and stabilization. A combination of experimental and theoretical calculations is useful for the pinpoint targeted design and optimization of CD molecular encapsulation of small entity molecules. β-CD was rationally screened as a better candidate for stabilizing EO, which provides an option for a meaningful path to realistic EO applications.

Background: The pathogenesis of metabolic syndrome was strongly associated with compromised metabolism homeostasis and gut microbiota imbalance. NAFLD is a progressive metabolic liver disease for which effective interventions are lacking. Bile acids exhibited appreciable metabolic regulatory effects and selective antimicrobial activity. Aim of the study: This study was designed to investigate the effect of BBBP, which mainly contained bile acids, on NAFLD from the perspectives of gut microbiota and metabolomics. Materials and methods: The present study was initiated on the anti-NAFLD effect of BBBP in HFD-fed mice. The efficacy of BBBP was evaluated by mice phenotypes, liver histopathological analysis and serum lipid and glucose levels. The activation of bile acid receptors such as Nr1h4, Nr1i2 and S1pr2 were detected by qRT-PCR analysis. Subsequently, untargeted metabolomics coupled with microbiomics was used to explore the mechanism of BBBP against NAFLD. Human L02 hepatocytes induced by OA and PA were used to investigate the effect of GABA on reducing lipid accumulation in vitro. Results: BBBP significantly and dose-dependently alleviated the obese phenotype, lipid accumulation and liver injury in mice subjected to 18 weeks HFD diet. Untargeted metabolomics and microbiomics analysis revealed that BBBP could alleviate the disturbance of lipid and amino acid metabolism and the imbalance of gut microbiota. Furthermore, BBBP oral gavage activated liver bile acid receptors, as indicated by elevated mRNA levels of Nr1h4, Nr1i2 and S1pr2. Surprisingly, we determined that BBBP, which mainly contained bile acids that possessed antimicrobial activity, could promote the growth of Lactobacillus. Correlation analysis showed a remarkable correlation between Lactobacillus and endogenous metabolites such as valine, serine, glutamine, et al. Among them, GABA which could be produced by Lactobacillus significantly reduced the lipid accumulation in L02 cells. Conclusions: The role of BBBP in regulating lipid metabolism might be achieved by activating bile acid receptors, or partially by promoting the levels of Lactobacillus and its metabolites such as GABA. Our study provided evidence that BBBP could be a novel therapeutic candidate for the treatment of NAFLD.

Abstract Background This multi-center study aimed to identify factors affecting fever and delayed defervescence in bacterial meningitis (BM) patients under 3 years of age because of the variability of fever in this patient population. Methods Only BM patients under 3 years treated at 49 centers in China from November 2018 to end-April 2021 were included in the study. Univariate and multivariate logistic regression analyses were performed to determine factors associated with afebrile presentation and fever of delayed defervescence. Results A total of 863 BM patients under 3 years were included in the study. Coagulase negative staphylococcus was associated with afebrile presentation (OR = 1.176), while septicaemia and ear-nose-throat infections were associated with fever (P

Abstract Aortic dissection (AD) is a life-threatening condition in which the inner layer of the aorta tears. It has been reported that metabolic syndrome (MS) has a close linkage with aortic dissection. However, the inter-relational mechanisms between them were still unclear. This article explored the hub gene signatures and potential molecular mechanisms in AD and MS. We obtained five bulk RNA-seq datasets of AD, one single cell RNA-seq (scRNA-seq) dataset of ascending thoracic aortic aneurysm (ATAA), and one bulk RNA-seq dataset of MS from the gene expression omnibus (GEO) database. Identification of differentially expressed genes (DEGs) and key modules via weighted gene co-expression network analysis (WGCNA), functional enrichment analysis, and machine learning algorithms (Random Forest and LASSO regression) were used to identify hub genes for diagnosing AD with MS. XGBoost further improved the diagnostic performance of the model. The receiver operating characteristic (ROC) and precision-recall (PR) curves were developed to assess the diagnostic value. Then, immune cell infiltration and metabolism-associated pathways analyses were created to investigate immune cell and metabolism-associated pathway dysregulation in AD and MS. Finally, the scRNA-seq dataset was performed to confirm the expression levels of identified hub genes. 406 common DEGs were identified between the merged AD and MS datasets. Functional enrichment analysis revealed these DEGs were enriched for applicable terms of metabolism, cellular processes, organismal systems, and human diseases. Besides, the positively related key modules of AD and MS were mainly enriched in transcription factor binding and inflammatory response. In contrast, the negatively related modules were significantly associated with adaptive immune response and regulation of nuclease activity. Through machine learning, nine genes with common diagnostic effects were found in AD and MS, including MAD2L2, IMP4, PRPF4, CHSY1, SLC20A1, SLC9A1, TIPRL, DPYD, and MAPKAPK2. In the training set, the AUC of the hub gene on RP and RR curves was 1. In the AD verification set, the AUC of the Hub gene on RP and RR curves were 0.946 and 0.955, respectively. In the MS set, the AUC of the Hub gene on RP and RR curves were 0.978 and 0.98, respectively. scRNA-seq analysis revealed that the SLC20A1 was found to be relevant in fatty acid metabolic pathways and expressed in endothelial cells. Our study revealed the common pathogenesis of AD and MS. These common pathways and hub genes might provide new ideas for further mechanism research.

Abstract Membrane-based organic solvent separations are rapidly emerging as a promising class of technologies for enhancing the energy efficiency of existing separation and purification systems. Polymeric membranes have shown promise in the fractionation or splitting of complex mixtures of organic molecules such as crude oil. Determining the separation performance of a polymer membrane when challenged with a complex mixture has thus far occurred in an ad hoc manner, and methods to predict the performance based on mixture composition and polymer chemistry are unavailable. Here, we combine physics-informed machine learning algorithms (ML) and mass transport simulations to create an integrated predictive model for the separation of complex mixtures containing up to 400 components via any arbitrary linear polymer membrane. We experimentally demonstrate the effectiveness of the model by predicting the separation of two crude oils within 6-7% of the measurements. Integration of ML predictors of diffusion and sorption properties of molecules with transport simulators enables for the rapid screening of polymer membranes prior to physical experimentation for the separation of complex liquid mixtures.

Background: Revascularized patients still experience adverse cardiovascular events. This is particularly true for elderly patients over the age of 65, as they often have more co-morbid vascular conditions. It is important to develop a tool to assist clinicians in comprehensively assessing these patients’ prognosis. The objective of this study is to create a comprehensive visual nomogram model combining clinical and physiological assessments to predict outcomes in elderly patients undergoing percutaneous coronary intervention (PCI). Methods: This study is a retrospective investigation of patients who underwent PCI between January 2016 and December 2017. A total of 691 patients with 1461 vessels were randomly divided into a training (n = 483) and a validation set (n = 208). A multivariate Cox regression model was employed using the training set to select variables for constructing a nomogram. The performance of the nomogram was assessed through the receiver operating characteristic curve (ROC) and calibration curves to evaluate its discrimination and predictive accuracy. To further assess the clinical usefulness, Kaplan–Meier curve analysis and landmark analysis were conducted. Results: Independent risk factors, including diabetes mellitus (DM), post-PCI quantitative flow ratio (QFR), previous myocardial infarction (MI), and previous PCI, were contained in the nomogram. The nomogram exhibited a good area under the curve (AUC) ranging from 0.742 to 0.789 in the training set, 0.783 to 0.837 in the validation set, and 0.764 to 0.786 in the entire population. Calibration curves demonstrated a well-fitted curve in all three sets. The Kaplan–Meier curves showed clear separation and the patients with higher scores in the nomogram model exhibited a higher incidence of target vessel revascularization (TVR) (7.99% vs. 1.24% for 2-year, p < 0.001 and 13.54% vs. 2.23% for 5-years, p < 0.001, respectively). Conclusions: This study has developed the visually intuitive nomogram to predict the 2-year and 5-year TVR rates for elderly patients who underwent PCI. This tool provides more accurate and comprehensive healthcare guidance for patients and their physicians.

CX3CL1, also named fractalkine or neurotactin, is the only known member of the CX3C chemokine family that can chemoattract several immune cells. CX3CL1 exists in both membrane-anchored and soluble forms, with each mediating distinct biological activities. CX3CL1 signals are transmitted through its unique receptor, CX3CR1, primarily expressed in the microglia of the central nervous system (CNS). In the CNS, CX3CL1 acts as a regulator of microglia activation in response to brain disorders or inflammation. Recently, there has been a growing interest in the role of CX3CL1 in regulating cell adhesion, chemotaxis, and host immune response in viral infection. Here, we provide a comprehensive review of the changes and function of CX3CL1 in various viral infections, such as human immunodeficiency virus (HIV), SARS-CoV-2, influenza virus, and cytomegalovirus (CMV) infection, to highlight the emerging roles of CX3CL1 in viral infection and associated diseases.

Abstract Background Intrauterine infection/inflammation can result in fetal and neonatal lung injury. However, the biological mechanisms of intrauterine infection/inflammation on fetal and neonatal lung injury and development are poorly known. To date, there are no reliable biomarkers for improving intrauterine infection/inflammation-induced lung injury. Methods An animal model of intrauterine infection/inflammation-induced lung injury was established with pregnant Sprague–Dawley rats inoculated with Escherichia coli suspension. The intrauterine inflammatory status was assessed through the histological examination of the placenta and uterus. A serial of histological examinations of the fetal and neonatal rats lung tissues were performed. The fetal and neonatal rat lung tissues were harvested for next generation sequencing at embryonic day 17 and postnatal day 3, respectively. Differentially expressed mRNAs and lncRNAs were identified by conducting high-throughput sequencing technique. The target genes of identified differentially expressed lncRNAs were analyzed. Homology analyses for important differentially expressed lncRNAs were performed. Results The histopathological results showed inflammatory infiltration, impaired alveolar vesicular structure, less alveolar numbers, and thickened alveolar septa in fetal and neonatal rat lung tissues. Transmission electron micrographs revealed inflammatory cellular swelling associated with diffuse alveolar damage and less surfactant-storing lamellar bodies in alveolar epithelial type II cells. As compared with the control group, there were 432 differentially expressed lncRNAs at embryonic day 17 and 125 differentially expressed lncRNAs at postnatal day 3 in the intrauterine infection group. The distribution, expression level, and function of these lncRNAs were shown in the rat genome. LncRNA TCONS_00009865, lncRNA TCONS_00030049, lncRNA TCONS_00081686, lncRNA TCONS_00091647, lncRNA TCONS_00175309, lncRNA TCONS_00255085, lncRNA TCONS_00277162, and lncRNA TCONS_00157962 may play an important role in intrauterine infection/inflammation-induced lung injury. Fifty homologous sequences in Homo sapiens were also identified. Conclusions This study provides genome-wide identification of novel lncRNAs which may serve as potential diagnostic biomarkers and therapeutic targets for intrauterine infection/inflammation-induced lung injury.

Abstract Aim To develop a competency framework applicable to Chinese extracorporeal membrane oxygenation (ECMO) nurses. Design A qualitative study was performed following the consolidated criteria for reporting qualitative research. Methods Semi‐structured interviews based on the critical incident technique were conducted among 21 ECMO care providers recruited from five well‐known ECMO centres in Guangzhou, China. Interview transcripts were coded and analysed using the constant comparative method. The data collection period lasted from November 2021 to April 2022. Results A competency framework for ECMO nurses was identified. It included four domains: knowledge, skills, behaviours and attitudes, containing 33 subcompetencies and 66 items. Relevance to clinical practice This framework can be a reference for the assessment and training of ECMO nurses.

BackgroundSubjective cognitive decline (SCD) is considered a preclinical stage of Alzheimer’s disease. However, reliable prevalence estimates of SCD in the Chinese population are lacking, underscoring the importance of such metrics for policymakers to formulate appropriate healthcare strategies.ObjectiveTo systematically evaluate SCD prevalence among older Chinese adults.MethodsPubMed, Web of Science, The Cochrane Library, Embase, CNKI, Wanfang, VIP, CBM, and Airiti Library databases were searched for studies on SCD in older Chinese individuals published before May 2023. Two investigators independently screened the literature, extracted the information, and assessed the bias risk of the included studies. A meta-analysis was then conducted using Stata 16.0 software via a random-effects model to analyze SCD prevalence in older Chinese adults.ResultsA total of 17 studies were included (n = 31,782). The SCD prevalence in older Chinese adults was 46.4% (95% CI, 40.6–52.2%). Further, subgroup analyzes indicated that SCD prevalence was 50.8% in men and 58.9% among women. Additionally, SCD prevalence in individuals aged 60–69, 70–79, and ≥ 80 years was 38.0, 45.2, and 60.3%, respectively. Furthermore, SCD prevalence in older adults with BMI 24.0 was 59.3, 54.0, and 52.9%, respectively. Geographically, SCD prevalence among older Chinese individuals was 41.3% in North China and 50.0% in South China. In terms of residence, SCD prevalence was 47.1% in urban residents and 50.0% among rural residents. As for retired individuals, SCD prevalence was 44.2% in non-manual workers and 49.2% among manual workers. In the case of education, individuals with an education level of “elementary school and below” had an SCD prevalence rate of 62.8%; “middle school, “52.4%; “high school, “55.0%; and “college and above, “51.3%. Finally, SCD prevalence was lower among married individuals with surviving spouses than in single adults who were divorced, widowed, or unmarried.ConclusionOur systematic review and meta-analysis identified significant and widespread SCD prevalence in the older population in China. Therefore, our review findings highlight the urgent requirement for medical institutions and policymakers across all levels to prioritize and rapidly develop and implement comprehensive preventive and therapeutic strategies for SCD.Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023406950, identifier: CRD42023406950.

PurposeTo develop and validate multi-parametric MRI (MP-MRI)-based radiomics models for the prediction of biological characteristics in endometrial cancer (EC).MethodsA total of 292 patients with EC were divided into LVSI (n = 208), DMI (n = 292), MSI (n = 95), and Her-2 (n = 198) subsets. Total 2316 radiomics features were extracted from MP-MRI (T2WI, DWI, and ADC) images, and clinical factors (age, FIGO stage, differentiation degree, pathological type, menopausal state, and irregular vaginal bleeding) were included. Intra-class correlation coefficient (ICC), spearman’s rank correlation test, univariate logistic regression, and least absolute shrinkage and selection operator (LASSO) were used to select radiomics features; univariate and multivariate logistic regression were used to identify clinical independent risk factors. Five classifiers were applied (logistic regression, random forest, decision tree, K-nearest neighbor, and Bayes) to construct radiomics models for predicting biological characteristics. The clinical model was built based on the clinical independent risk factors. The combined model incorporating the radiomics score (radscore) and the clinical independent risk factors was constructed. The model was evaluated by ROC curve, calibration curve (H-L test), and decision curve analysis (DCA).ResultsIn the training cohort, the RF radiomics model performed best among the five classifiers for the three subsets (MSI, LVSI, and DMI) according to AUC values (AUCMSI: 0.844; AUCLVSI: 0.952; AUCDMI: 0.840) except for Her-2 subset (Decision tree: AUC=0.714), and the combined model had higher AUC than the clinical model in each subset (MSI: AUCcombined =0.907, AUCclinical =0.755; LVSI: AUCcombined =0.959, AUCclinical =0.835; DMI: AUCcombined = 0.883, AUCclinical =0.796; Her-2: AUCcombined =0.812, AUCclinical =0.717; all P

Background Alzheimer’s disease (AD) is a neurodegenerative disorder characterised by cognitive decline, behavioural and psychological symptoms of dementia (BPSD) and impairment of activities of daily living (ADL). Early differentiation of AD from mild cognitive impairment (MCI) is necessary.Methods A total of 458 patients newly diagnosed with AD and MCI were included. Eleven batteries were used to evaluate ADL, BPSD and cognitive function (ABC). Machine learning approaches including XGboost, classification and regression tree, Bayes, support vector machines and logical regression were used to build and verify the new tool.Results The Alzheimer’s Disease Assessment Scale (ADAS-cog) word recognition task showed the best importance in judging AD and MCI, followed by correct numbers of auditory verbal learning test delay recall and ADAS-cog orientation. We also provided a selected ABC-Scale that covered ADL, BPSD and cognitive function with an estimated completion time of 18 min. The sensitivity was improved in the four models.Conclusion The quick screen ABC-Scale covers three dimensions of ADL, BPSD and cognitive function with good efficiency in differentiating AD from MCI.

Due to the limited application of the natural river sand in China, recycled sand (RS) has been considered as an important replacement of natural sand in sustainable construction. The morphology of recycled sand is critical to its effective application in mortar and concrete. An environmentally friendly approach is introduced in this work to improve the morphology of recycled sand during its crushing process. This paper presents a newly developed image acquisition device, which obtained 25,328 RS images to use as a dataset for the construction of a segmentation model based on deep learning technology with an automatic segmentation of RS characteristics. Evaluation indices including accuracy (ACC), Recall, intersection over union (IoU), and F1-score index are reaching up to 99.8%, 88.1%, 84.9% and 84.3%, respectively. RS morphological characteristics including the flat and elongation ratio (FER), angularity index (AI), roundness (R) are automatically extracted by the proposed model, and the predicted results agreed well with the experimental ones. Finally, the effect of FER of RS on mortar’s mechanical properties is investigated by a series of experiments. Results reveal that the flowability, flexural strength and compressive strength of mortar decreased invariably with the lower FER of sand.

AbstractBackground Hantaan virus (HTNV) infection can cause severe hemorrhagic fever with renal syndrome (HFRS). Inflammatory monocytes (iMOs) are involved in early antiviral responses. Previous studies have found that blood iMOs numbers increase in the acute phase of HFRS. Here, we further identified the phenotypic characteristics of iMOs in HFRS and explored whether phenotypic changes in iMOs were associated with HFRS severity.Materials and Methods Blood samples from 85 HFRS patients were used for phenotypic analysis of iMOs by flow cytometry. Plasma HTNV load was determined using RT-PCR. THP-1 cells overexpressing CD226 were used to investigate the effects of CD226 on HLA-DR/DP/DQ and CD80 expression. A mouse model was used to test macrophage phenotype following HTNV infection.Results The proportion of CD226- iMOs in the acute phase of HFRS was 66.83 (35.05-81.72) %, which was significantly higher than that in the convalescent phase (5.32 (1.36-13.52) %) and normal controls (7.39 (1.15-18.11) %) (p

Lutein is a strong antioxidant with anti-inflammatory, anti-oxidative and cardioprotective effects and could be a promising candidate for the treatment of hypertensive heart disease (HHD), but is not clinically appealing because of its low oral bioavailability and main distribution in the eyes. To address this, a biomimetic drug delivery system-MMLNPs was established by coating macrophage membranes (MMs) onto lutein-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (LNPs). This study characterized the physical properties of biomimetic nanoparticles and examined the targeting capability, therapeutic effects and mechanism, and biosecurity of administering them for cardiac fibrosis therapy in the transverse aortic constriction (TAC) model and in vitro. Transmission electron microscope mapping and dynamic light scattering analysis proved that MMLNPs were spherical nanoparticles camouflaged by a layer of cell membrane and had negative zeta potential. Confocal laser scanning microscopy and flow cytometry analysis showed that MMs on the biomimetic nanoparticles hindered the phagocytosis of macrophages and facilitated the targeting of activated endothelial cells. Ex vivo fluorescence imaging experiments demonstrated the targeting of biomimetic nanoparticles to the injured heart. EdU assay indicated that MMLNPs have the same potential to inhibit angiotensin (Ang) II-induced cardiac fibroblast proliferation as free lutein. Furthermore, echocardiography showed that MMLNPs improved cardiac function and structure, and Masson staining and western blotting showed that MMLNPs ameliorated cardiac fibrosis. We found MMLNPs inhibited the interleukin (IL)-11/ERK signaling pathway which was up-regulated in the TAC model compared to the sham-operated mouse. Biochemical testing and hematoxylin and eosin staining proved that the long-term use of MMLNPs lacked biological toxicity. Collectively, MMLNPs might be a promising nanodrug delivery approach to attenuate pressure overload (PO)-induced cardiac fibrosis.

Abstract Objective To describe myeloid sarcoma (MS) that mimic gynecological tumors and provide guidelines for improving the diagnosis and treatment of patients. Methods This case series study retrospectively analyzed the clinicopathological characteristics and oncological outcomes of female patients who were histologically diagnosed with MS after initially presenting with reproductive-system tumors at the Peking Union Medical College Hospital between January 2000 and March 2022. Results There were eight cases in which MS mimicked cervical cancer, ovarian cancer, or hysteromyoma. Six patients had isolated MS, and the other two had acute myeloid leukemia (AML)-M2. The average age was 39.00 ± 14.26. They each sought advice from a gynecological oncologist at the initial visit, complaining of irregular bleeding (3/8), low abdominal pain (3/8), dysmenorrhea (1/8), or an accidentally found mass (1/8). CT/MRI exams revealed that the average tumor size reached 5.65 ± 2.35 cm, with 50% of the tumors being larger than 8 cm. The final diagnoses were confirmed by biopsy (2/8) or postoperative pathology (6/8); the most frequent positive immunohistochemical markers were Ki-67 (60–90%), MPO (100%), LCA (62.5%), CD43 (62.5%), CD117 (62.5%), CD99 (50%), vimentin (37.5%), and lysozyme (25%). MLL/AF9 gene fusions and CEBPA, JAK2, NRAS, and FLT3-TKD mutations were found in the patients. Six (75%) of the patients showed a complete response after upfront treatment using chemotherapy + surgery and experienced no recurrence during follow-up. The overall survival (OS) rate was 72.9%, and the 5-year OS rate was 72.9% (95%CI: 0.4056–1.000). The median OS was 26 months (range: 3–82). Conclusion For patients with isolated MS, treatment by chemotherapy and surgery are radical procedure, and initial treatment using chemotherapy alone should be considered for MS with synchronous intramedullary AML. Poor response to chemotherapy, short interval to leukemia occurrence, and heavy tumor burden (> 10 cm) could indicate a poor prognosis for patients with MS.