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Abstract Patients who suffer from sepsis typically experience acute lung injury (ALI). Extracellular vesicles (EVs) contain miRNAs, which are potentially involved in ALI. However, strategies to screen more effective EV-miRNAs as therapeutic targets are yet to be elucidated. In this study, functional EV-miRNAs were identified based on multiomics analysis of single-cell RNA sequencing of targeted organs and serum EV (sEV) miRNA profiles in patients with sepsis. The proportions of neutrophils and macrophages were increased significantly in the lungs of mice receiving sEVs from patients with sepsis compared with healthy controls. Macrophages released more EVs than neutrophils. MiR-125a-5p delivery by sEVs to lung macrophages inhibited Tnfaip3, while miR-221-3p delivery to lung neutrophils inhibited Fos. Macrophage membrane nanoparticles (MM NPs) loaded with an miR-125a-5p inhibitor or miR-221-3p mimic attenuated the response to lipopolysaccharide (LPS)-induced ALI. Transcriptome profiling revealed that EVs derived from LPS-stimulated bone marrow-derived macrophages (BMDMs) induced oxidative stress in neutrophils. Blocking toll-like receptor, CXCR2, or TNFα signaling in neutrophils attenuated the oxidative stress induced by LPS-stimulated BMDM-EVs. This study presents a novel method to screen functional EV-miRNAs and highlights the pivotal role of macrophage-derived EVs in ALI. MM NPs, as delivery systems of key sEV-miRNA mimics or inhibitors, alleviated cellular responses observed in sepsis-induced ALI. This strategy can be used to reduce septic organ damage, particularly lung damage, by targeting EVs.

Let G be a graph with V(G) and E(G), as vertex set and edge set, respectively. The atom-bond sum-connectivity (ABS) index is a vertex-based topological index which is defined as [Formula: see text] where [Formula: see text] is the degree of the vertex a. In this paper, we obtain sharp upper bounds for the ABS index of molecular trees in terms of order and number of branching vertices and vertices of degree two.

Abstract Interleukin-6 (IL-6) is a pleiotropic cytokine and exerts its complex biological functions mainly through three different signal modes, called cis-, trans-, and cluster signaling. When IL-6 binds to its membrane or soluble receptors, the co-receptor gp130 is activated to initiate downstream signaling and induce the expression of target genes. In the liver, IL-6 can perform its anti-inflammatory activities to promote hepatocyte reprogramming and liver regeneration. On the contrary, IL-6 also exerts the pro-inflammatory functions to induce liver aging, fibrosis, steatosis, and carcinogenesis. However, understanding the roles and underlying mechanisms of IL-6 in liver physiological and pathological processes is still an ongoing process. So far, therapeutic agents against IL‑6, IL‑6 receptor (IL‑6R), IL-6-sIL-6R complex, or IL-6 downstream signal transducers have been developed, and determined to be effective in the intervention of inflammatory diseases and cancers. In this review, we summarized and highlighted the understanding of the double-edged effects of IL-6 in liver homeostasis, aging, inflammation, and chronic diseases, for better shifting the “negative” functions of IL-6 to the “beneficial” actions, and further discussed the potential therapeutic effects of targeting IL-6 signaling in the clinics.

Abstract Background Leaf morphology plays a crucial role in photosynthetic efficiency and yield potential in crops. Cigar tobacco plants, which are derived from common tobacco (Nicotiana tabacum L.), possess special leaf characteristics including thin and delicate leaves with few visible veins, making it a good system for studying the genetic basis of leaf morphological characters. Results In this study, GWAS and QTL mapping were simultaneously performed using a natural population containing 185 accessions collected worldwide and an F2 population consisting of 240 individuals, respectively. A total of 26 QTLs related to leaf morphological traits were mapped in the F2 population at three different developmental stages, and some QTL intervals were repeatedly detected for different traits and at different developmental stages. Among the 206 significant SNPs identified in the natural population using GWAS, several associated with the leaf thickness phenotype were co-mapped via QTL mapping. By analyzing linkage disequilibrium and transcriptome data from different tissues combined with gene functional annotations, 7 candidate genes from the co-mapped region were identified as the potential causative genes associated with leaf thickness. Conclusions These results presented a valuable cigar tobacco resource showing the genetic diversity regarding its leaf morphological traits at different developmental stages. It also provides valuable information for novel genes and molecular markers that will be useful for further functional verification and for molecular breeding of leaf morphological traits in crops in the future.

Abstract Background Early menarche is an established risk factor for breast cancer but its molecular contribution to tumor biology and prognosis remains unclear. Methods We profiled transcriptome-wide gene expression in breast tumors (N = 846) and tumor-adjacent normal tissues (N = 666) from women in the Nurses’ Health Studies (NHS) to investigate whether early menarche (age

Abstract Background Objective and quantifiable markers are crucial for developing novel therapeutics for mental disorders by 1) stratifying clinically similar patients with different underlying neurobiological deficits and 2) objectively tracking disease trajectory and treatment response. Schizophrenia is often confounded with other psychiatric disorders, especially bipolar disorder, if based on cross-sectional symptoms. Awake and sleep EEG have shown promise in identifying neurophysiological differences as biomarkers for schizophrenia. However, most previous studies, while useful, were conducted in European and American populations, had small sample sizes, and utilized varying analytic methods, limiting comprehensive analyses or generalizability to diverse human populations. Furthermore, the extent to which wake and sleep neurophysiology metrics correlate with each other and with symptom severity or cognitive impairment remains unresolved. Moreover, how these neurophysiological markers compare across psychiatric conditions is not well characterized. The utility of biomarkers in clinical trials and practice would be significantly advanced by well-powered transdiagnostic studies. The Global Research Initiative on the Neurophysiology of Schizophrenia (GRINS) project aims to address these questions through a large, multi-center cohort study involving East Asian populations. To promote transparency and reproducibility, we describe the protocol for the GRINS project. Methods The research procedure consists of an initial screening interview followed by three subsequent sessions: an introductory interview, an evaluation visit, and an overnight neurophysiological recording session. Data from multiple domains, including demographic and clinical characteristics, behavioral performance (cognitive tasks, motor sequence tasks), and neurophysiological metrics (both awake and sleep electroencephalography), are collected by research groups specialized in each domain. Conclusion Pilot results from the GRINS project demonstrate the feasibility of this study protocol and highlight the importance of such research, as well as its potential to study a broader range of patients with psychiatric conditions. Through GRINS, we are generating a valuable dataset across multiple domains to identify neurophysiological markers of schizophrenia individually and in combination. By applying this protocol to related mental disorders often confounded with each other, we can gather information that offers insight into the neurophysiological characteristics and underlying mechanisms of these severe conditions, informing objective diagnosis, stratification for clinical research, and ultimately, the development of better-targeted treatment matching in the clinic.

Abstract Ancient murals have suffered from continuous damage over time, and especially paint loss disease. Therefore, disease labeling, as the basis for ancient mural restoration, plays an important role in the protection of cultural relics. The predominant method of disease labeling is currently manual labeling, which is highly dependent on expert experience, time consuming, inefficient and results in inconsistent accuracy of the marking effect. In this paper, we propose a labeling framework for paint loss disease of ancient murals based on hyperspectral image classification and segmentation. The proposed framework involves first the extraction of features from the hyperspectral image, and then image segmentation is performed based on the spatial features to obtain more accurate region boundaries. Then, the hyperspectral image’s regions are classified based on their spatial-spectral characteristics, and the candidate areas of paint loss disease are obtained. Finally, by leveraging the true color image segmentation results, the proposed disease labeling strategy combines the results of classification and segmentation to propose the final paint loss disease labeling areas. The experimental results show that the proposed method can not only combine the hyperspectral space and spectral information effectively to obtain accurate labeling of paint loss disease, but can also mark the paint loss disease not easily observed using ordinary digital cameras. Compared with the state-of-the-art methods, the proposed framework could be promising for accurate and effective paint loss disease labeling for ancient murals.

Starch was the main source of carbohydrates in people's daily diet, and its digestibility was an important factor affecting the body's postprandial blood glucose level. In this paper, the effect of xylose on the in vitro digestive properties of corn starch and its mechanism of action were investigated. The in vitro digestibility of starch was evaluated by an in vitro simulated digestion system after different additions of xylose (5%, 10%, and 15%), and the mechanisms of xylose on α-amylase and α-glucosidase, as well as its effect on blood glucose fluctuation through enzyme inhibition kinetics, molecular docking, and human glycemic index (GI) tests. The results showed that the digestive hydrolysis of corn starch was inhibited by different amounts of xylose, and the IC50 values of xylose on α-glucosidase and α-amylase were 205.35 and 4.75 mg/mL, respectively, which belonged to the mixed type inhibitors. Xylose interacted with amino acid residues of α-glucosidase and α-amylase through hydrogen bonding with binding energies of −3.05 and −5.30 kcal/mol, respectively. Additionally, the GI value of plant-based peptidoglycan milk decreased from 58 to 45 after the addition of xylose, which demonstrated that xylose was effective in decreasing the fluctuation of postprandial blood glucose. The results could provide scientific data to support the research and application of xylose in nutritional and health foods.

Abstract Background Flea bites could trigger a series of complex molecular responses in the host. However, our understanding of the responses at the molecular level is still relatively limited. This study quantifies the changes in gene expression in mice after flea bites by RNA sequencing (RNA-seq) from their spleens, revealing the potential biological effects of host response to flea bites. Methods RNA-seq was used for transcriptome analysis to screen for differentially expressed genes (DEGs) between the control mice group and the flea bite mice group. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on DEGs. Protein–protein interaction (PPI) network analysis on DEGs related to immune processes was performed. Finally, we randomly selected several genes from the screened DEGs to validate the results from the transcriptome data by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Results A total of 521 DEGs were identified, including 277 upregulated and 244 downregulated. There were 258 GO terms significantly enriched by upregulated DEGs and 419 GO terms significantly enriched by downregulated DEGs. Among the upregulated DEGs, 22 GO terms were associated with immune cells (e.g., B cells and T cells) and immune regulatory processes, while among the downregulated DEGs, 58 GO terms were associated with immune cells and immune regulatory processes. Through PPI analysis, we found that CD40 molecules with significantly downregulated expression levels after flea bites may play an important role in host immune regulation. Through KEGG pathway enrichment analysis, a total of 26 significantly enriched KEGG pathways were identified. The RT-qPCR analysis results indicated that the transcriptome sequencing results were reliable. Conclusions Through in-depth analysis of transcriptome changes in mice caused by flea bites, we revealed that flea bites could stimulate a series of biological and immunological responses in mice. These findings not only provided a deeper understanding of the impact of flea bites on the host but also provided a basis for further research on the interaction between ectoparasites and the host. We believe that digging deeper into the significance of these transcriptome changes will help reveal more about the adaptive response of the host to ectoparasites. Graphical Abstract

Abstract Background —Recent evidence suggests that hyperuricemia may act as independent risk factors for erectile dysfunction (ED), in addition to the already established factors. The current evidence supporting this relationship remains insufficient. Methods and results —A total of 3,810 participants from the NHANES pool between 2001 and 2004 were included in our study, comprising 1,093 individuals with ED and 2,717 individuals without ED. Univariable and multivariable logistic regression analyses were conducted to examine the relationship between uric acid (UA) and the prevalence of ED. In the fully adjusted model, no significant association was observed between UA and ED (OR = 1.02, 95% CI: 0.84–1.24), and no significant differences were noted among the various UA levels (p = 0.5). In our sensitivity analyses, employing a stricter definition for ED, no significant results were found in the fully adjusted model (OR = 0.85, 95% CI: 0.60–1.19). Furthermore, no significant differences were observed among the various UA levels (p = 0.083). Conclusions —Our study did not establish a correlation between UA levels and ED. Nonetheless, further research with larger sample cohorts is required to verify these findings.

Abstract Gene therapy aims to modify or manipulate gene expression and change the biological characteristics of living cells to achieve the purpose of treating diseases. The safe, efficient, and stable expression of exogenous genes in cells is crucial for the success of gene therapy, which is closely related to the vectors used in gene therapy. Currently, gene therapy vectors are mainly divided into two categories: viral vectors and non-viral vectors. Viral vectors are widely used due to the advantages of persistent and stable expression, high transfection efficiency, but they also have certain issues such as infectivity, high immunological rejection, randomness of insertion mutation, carcinogenicity, and limited vector capacity. Non-viral vectors have the advantages of non-infectivity, controllable chemical structure, and unlimited vector capacity, but the transfection efficiency is low. With the rapid development of nanotechnology, the unique physicochemical properties of nanomaterials have attracted increasing attention in the field of drug and gene delivery. Among many nanomaterials, iron-based nanomaterials have attracted much attention due to their superior physicochemical properties, such as Fenton reaction, magnetic resonance imaging, magnetothermal therapy, photothermal therapy, gene delivery, magnetically-assisted drug delivery, cell and tissue targeting, and so on. In this paper, the research progress of iron-based nanomaterials in gene delivery and tumor gene therapy is reviewed, and the future application direction of iron-based nanomaterials is further prospected.

Abstract Background Investigating the unexplored territory of lncRNA m6A modification in colorectal cancer (CRC) vasculature, this study focuses on LINC01106 and YTHDF1. Methods Clinical assessments reveal upregulated LINC01106 promoting vascular generation via the miR-449b-5p-VEGFA pathway. Results YTHDF1, elevated in CRC tissues, emerges as an adverse prognostic factor. Functional experiments showcase YTHDF1’s inhibitory effects on CRC cell dynamics. Mechanistically, Me-CLIP identifies m6A-modified LINC01106, validated as a YTHDF1 target through Me-RIP. Conclusions This study sheds light on the YTHDF1-mediated m6A modification of LINC01106, presenting it as a key player in suppressing CRC vascular generation.

AIM: To investigate the morphological characteristics of retinal vessels in patients with different severity of diabetic retinopathy (DR) and in patients with or without diabetic macular edema (DME). METHODS: The 239 eyes of DR patients and 100 eyes of healthy individuals were recruited for the study. The severity of DR patients was graded as mild, moderate and severe non-proliferative diabetic retinopathy (NPDR) according to the international clinical diabetic retinopathy (ICDR) disease severity scale classification, and retinal vascular morphology was quantitatively analyzed in ultra-wide field images using RU-net and transfer learning methods. The presence of DME was determined by optical coherence tomography (OCT), and differences in vascular morphological characteristics were compared between patients with and without DME. RESULTS: Retinal vessel segmentation using RU-net and transfer learning system had an accuracy of 99% and a Dice metric of 0.76. Compared with the healthy group, the DR group had smaller vessel angles (33.68±3.01 vs 37.78±1.60), smaller fractal dimension (Df) values (1.33±0.05 vs 1.41±0.03), less vessel density (1.12±0.44 vs 2.09±0.36) and fewer vascular branches (206.1±88.8 vs 396.5±91.3), all P

Background The heterogeneity of myelodysplastic syndromes (MDS) is strong, with poor efficacy of existing therapeutic regimens and large individual differences in patient prognosis. B-cell lymphomato-2 (Bcl-2) protein is highly expressed in patients with myeloid tumors, which has been proved by previous to be associated with disease progression, chemotherapy resistance, and shortened overall survival. The Bcl-2 inhibitor Veneckla (VEN) is approved for elderly patients with newly diagnosed acute myeloid leukemia (AML) who are not eligible for intensive therapy, and there is less data on its use in MDS patients. The difference in Bcl-2 expression in MDS patients and its correlation with the efficacy and prognosis of VEN therapy haven't been reported. Objective To analyse the expression of Bcl-2 protein in MDS patients and assess its correlation with the efficacy and prognosis of VEN treatment. Methods The clinical data of 71 patients with MDS admitted to Sichuan Academy of Medical Sciences·Sichuan Provincial People's Hospital from July 2018 to December 2022 were retrospectively analyzed. Baseline data of patients including gender, age, blood routine, blood biochemistry, bone marrow hemocytology, flow cytometry, chromosome karyotype, myeloid gene mutation, fusion gene mutation and MDS-EB typing were collected. The expression of Bcl-2 protein was detected by immunohistochemical staining. According to the modified International Prognostic Score System (IPSS-R), the patients were divided into 5 risk levels of very low risk (0 case), low risk (1 case), medium risk (7 cases), high risk (40 cases) and very high risk (23 cases). Patients with bone marrow Bcl-2 positivity≥10% were defined as Bcl-2 positive and0.05) . Conclusion Bcl-2 protein contributes to MDS fusion gene mutation and myeloid gene mutation; Bcl-2 positive expression was not associated with the survival of MDS patients. There was no difference in survival rate between Bcl-2 positive and Bcl-2 negative patients who received the VA combination regimen.

Background Cardiovascular disease (CVD) is the leading cause of death in China and the world as a whole, and lipid metabolism disorder is the key factor for this disease. A comprehensive understanding of the prevalence of dyslipidemia in children and adolescents can contribute to the early prevention of dyslipidemia in adulthood. Objective To systematically evaluate the status quo of the prevalence of dyslipidemia in Chinese children and adolescents. Methods Cross-sectional studies on the morbidity rate of dyslipidemia among Chinese children and adolescents and published from January 2015 to July 2023 were retrieved from databases of CBM, CNKI, Wanfang, VIP, Embase, Web of Science and Cochrane Library. Processes of literature screening, data extraction and risk bias analysis were performed by two researchers. A meta-analysis was performed by taking advantage of Stata 17.0. Results 34 cross-sectional studies were collected and a total of 134 438 children and adolescents were involved. Results of the meta-analysis indicated that the overall morbidity rate of dyslipidemia in Chinese children and adolescents was 19% (95%CI=16%-21%), and the morbidity rates of high cholesterol (TC), high triacylglycerol (TG), high low-density lipoprotein cholesterol (LDL-C), low high-density lipoprotein cholesterol (HDL-C) were 6% (95%CI=5%-7%), 9% (95%CI=6%-12%), 4% (95%CI=3%-5%) and 10% (95%CI=7%-13%) respectively. Regarding time distribution, the detection rate of dyslipidemia was fluctuant and showed a decreasing trend; the detection rate of high TC and high LDL-C showed an increasing trend in general, but it fell slightly in 2023; the detection rate of high TG and low HDL-C fluctuated greatly: the detection rate of high TG gradually decreased from 2018 to 2022 and rebounded slightly in 2023. The results of subgroup analysis showed that, concerning age, the overall morbidity rate of dyslipidemia in children and adolescents and that of high TC showed an ascending tendency with the increasing of age (10% and 2% for those aged from 3 to 6, 17% and 10% for those aged from 7 to 11, and 27% and 14% for those aged from 12 to18), the morbidity rate of lowered HDL-C was higher among 12-to-18-year olds (20%) than among 7-to-11-year olds (9%), and the morbidity rate of high TC among 3-to-6-year olds (9%) was higher than that among 7-to-11-year olds and 12-to-18-year-olds (4% and 3%) (P

Background Rifampicin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB) is featured by challenges in the treatment, low cure rate, and high infectivity. Fluoroquinolones (FQs), as the core drugs for the treatment of RR/MDR-TB, have a severe trend of resistance. Analyzing influencing factors for FQs can help to increase the cure rate of RR/MDR-TB and to control the occurrence of the pre-extensive drug resistance (pre-XDR) and extensive drug resistance. Objective To analyze the drug resistance of FQs in hospitalized patients with pulmonary tuberculosis and the influencing factors, and to construct and validate a Nomogram prediction model for the risk factors of drug resistance of FQs. Methods A total of 583 patients with pulmonary tuberculosis who were hospitalized in Guiyang Public Health Clinical Center from January 2021 to February 2022 and tested for drug sensitivity were retrospectively selected as study subjects. They were divided into the initial treatment group (296 patients) and the retreatment group (287 patients) according to the history of previous treatment. Moreover, they were divided into the FQs-resistant group (63 patients) and FQs-sensitive group (520 patients) according to their FQs-resistance status. The distribution of total resistance to 13 antituberculosis drugs in 583 patients was analyzed, and the baseline characteristics of patients in the FQs-resistant group and FQs-sensitive group were compared. After screening the characteristic variables using least absolute shrinkage and selection operator (LASSO) regression model, multivariate Logistic regression was performed to analyze the independent risk factors for the resistance of FQs. A Nomogram prediction model was constructed, and its performance was validated by calculating the area under the curve (AUC) of receiver operating characteristic (ROC), and plotting the calibration curve. Results Among 583 patients, 520 cases were sensitive to FQs and 63 cases were resistant (resistance rate of 10.81%). The resistance rate of FQs was secondary to the total resistance rate of first-line antituberculosis drugs, including the isoniazid (36.36%), rifampicin (32.76%), streptomycin (21.61%), and ethambutol (12.86%). The resistance rates of rifampicin, isoniazid, ethambutol, streptomycin, levofloxacin, moxifloxacin and rifampicin resistance (RR), multidrug resistance (MDR), and pre-XDR were significantly higher in patients of the retreatment group than those of the initial treatment group (P

Introducing additional oxidizers in aluminized explosives is an effective way to improve energy performance by enhancing the secondary combustion reaction. In this work, perfluorocarbon as oxidizer has been introduced into TATB/Al based energetic materials to improve combustion reaction and energy output performance. The uniform TATB/Al/perfluorocarbon composites are prepared through acoustic resonance mixed technology, and the energy and pressure output performance are fully studied in air blast and underwater explosion. A significantly exothermic peak derived from the reaction between fluorine and Al is observed between 540 ℃ and 580 ℃ for TATB/Al/perfluorocarbon. The heat of explosion of TATB/Al/perfluorocarbon is increased first and then decreased with F/Al ratio from 0 to 0.608. The highest heat of explosion is 6021 J/g for TATB/Al/perfluorocarbon with F/Al ratio of 0.274. Furthermore, the enhanced working capacity, the significantly enlarged fireball and relatively high overpressure are obtained for TATB/Al/perfluorocarbon. More importantly, the shock impulse and first bubble oscillation time of TATB/Al/perfluorocarbon have been increased by 23.2% and 21.18% during underwater explosion, respectively. The results further illustrate that adding perfluorocarbon is a feasible approach to enhance energy output due to combustion reaction between fluorine and Al, which can be applied in explosives and propellants.

The undercooled solidification of the Inconel 718 superalloy under high magnetic field was performed for the first time at high undercoolings (∼ 200 °C). The results show that the high magnetic field can significantly refine the grains of the undercooled alloys, with the average grain size decreasing from 241 ± 92 μm at 0 T to about a third under high magnetic fields (3 T ∼ 9 T). Detailed EBSD analysis provides clear evidence that Icosahedral Short-Range Order (ISRO) enhanced nucleation occurs. The present work opens up a new way for grain refinement of alloys.

Pericentric inversion of chromosome 9 (inv[9]) is a common chromosomal structural variant, but its impact on clinical outcomes remains debated. The screening criteria of sperm banks are rarely mentioned to individuals with inv(9). In this study, we evaluated the fertility of sperm donors with inv(9) who met eligibility criteria for sperm banks (inv[9]-eligible donors). From March 2004 to May 2022, chromosomal analysis of 16 124 sperm donors at CITIC-Xiangya Human Sperm Bank in Hunan Province (Changsha, China) found that 251 (1.6%) had chromosome variations, with inv(9) being the most prevalent at 1.1%. All 169 inv(9)-eligible donors were contacted to collect fertility outcome data, along with 206 eligible donors without inv(9) as controls. In addition, semen samples from inv(9)-eligible donors and eligible donors underwent assessments of sperm fluorescence in situ hybridization (FISH), mitochondrial membrane potential, DNA fragmentation index, acrosome integrity, reactive oxygen species (ROS), and sperm morphology. Results showed that inv(9) did not significantly increase reproductive risks overall. Despite detecting ROS level differences, the clinical impact may be insignificant. This study provides new data on the inv(9) population that can serve as a valuable reference for decision-making by sperm banks as well as for genetic counseling and clinical guidance for individuals carrying inv(9) variant.