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Abstract Background Acute myeloid leukemia (AML) is the most common malignancy of the hematological system, and there are currently a number of studies regarding abnormal alterations in energy metabolism, but fewer reports related to fatty acid metabolism (FAM) in AML. We therefore analyze the association of FAM and AML tumor development to explore targets for clinical prognosis prediction and identify those with potential therapeutic value. Methods The identification of AML patients with different fatty acid metabolism characteristics was based on a consensus clustering algorithm. The CIBERSORT algorithm was used to calculate the proportion of infiltrating immune cells. We used Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression analysis to construct a signature for predicting the prognosis of AML patients. The Genomics of Drug Sensitivity in Cancer database was used to predict the sensitivity of patient samples in high- and low-risk score groups to different chemotherapy drugs. Results The consensus clustering approach identified three molecular subtypes of FAM that exhibited significant differences in genomic features such as immunity, metabolism, and inflammation, as well as patient prognosis. The risk-score model we constructed accurately predicted patient outcomes, with area under the receiver operating characteristic curve values of 0.870, 0.878, and 0.950 at 1, 3, and 5 years, respectively. The validation cohort also confirmed the prognostic evaluation performance of the risk score. In addition, higher risk scores were associated with stronger fatty acid metabolisms, significantly higher expression levels of immune checkpoints, and significantly increased infiltration of immunosuppressive cells. Immune functions, such as inflammation promotion, para-inflammation, and type I/II interferon responses, were also significantly activated. These results demonstrated that immunotherapy targeting immune checkpoints and immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs) and M2 macrophages, are more suitable for patients with high-risk scores. Finally, the prediction results of chemotherapeutic drugs showed that samples in the high-risk score group had greater treatment sensitivity to four chemotherapy drugs in vitro. Conclusions The analysis of the molecular patterns of FAM effectively predicted patient prognosis and revealed various tumor microenvironment (TME) characteristics.

Abstract Background Transforming growth factor (TGF)-β signaling functions importantly in regulating tumor microenvironment (TME). This study developed a prognostic gene signature based on TGF-β signaling-related genes for predicting clinical outcome of patients with lung adenocarcinoma (LUAD). Methods TGF-β signaling-related genes came from The Molecular Signature Database (MSigDB). LUAD prognosis-related genes were screened from all the genes involved in TGF-β signaling using least absolute shrinkage and selection operator (LASSO) Cox regression analysis and then used to establish a risk score model for LUAD. ESTIMATE and CIBERSORT analyzed infiltration of immune cells in TME. Immunotherapy response was analyzed by the TIDE algorithm. Results A LUAD prognostic 5-gene signature was developed based on 54 TGF-β signaling-related genes. Prognosis of high-risk patients was significantly worse than low-risk patients. Both internal validation and external dataset validation confirmed a high precision of the risk model in predicting the clinical outcomes of LUAD patients. Multivariate Cox analysis demonstrated the model independence in OS prediction of LUAD. The risk model was significantly related to the infiltration of 9 kinds of immune cells, matrix, and immune components in TME. Low-risk patients tended to respond more actively to anti-PD-1 treatment, while high-risk patients were more sensitive to chemotherapy and targeted therapy. Conclusions The 5-gene signature based on TGF-β signaling-related genes showed potential for LUAD management.

Objective To investigate the inhibition of house dust mite induced oxidative stress with human bronchial epithelial cell line BEAS-2B by aldose reductase inhibitor (ARIs). Methods BEAS-2B was divided into control group, model group, NF-κB inhibitor group (PDTC group) and ARIs intervention group (ARIs group). Oxidative stress reaction (MDA and ROS content, SOD activity) was detected by ELISA. The contents of IL-5, IL-13 and IFN-γ were measured by ELISA. MTT was used to detect cell viability. Cell apoptosis was detected by flow cytometry. The expressions of NF-κB, NF-κB P65 and P38 MAPK proteins were detected by Western blot. Results SOD activity, IFN-γ content and cell survival rate in model group were lower than those in control group (P＜0.05), MDA, IL-5, IL-13 content and cell apoptosis rate were higher than those in control group (P＜0.05). Compared with model group, SOD activity, IFN-γ content and cell survival rate in PDTC and ARIs groups were increased(P＜0.05), MDA, IL-5, IL-13 content and cell apoptosis rate were decreased (P＜0.05). Compared with control group, the expression of NF-κB, NF-κB P65 and P38 MAPK protein in model group was significantly increased(P＜0.05). The expression of NF-κB, NF-κB P65 and P38 MAPK protein in PDTC group and ARIs group were significantly decreased (P＜0.05). Conclusions Aldose reductase inhibitors improve the oxidative stress response of human bronchial epithelial cells induced by house dust mites, promote the proliferation of BEAS-2B cells and inhibit apoptosis.

Abstract Background Circulating fibrinogen to pre-albumin ratio (FPR) and albumin to fibrinogen ratio (AFR) are effective factors for predicting the prognosis of colorectal cancer (CRC). However, the role of these two ratios in diagnosing early-stage CRC and identifying the stage II CRC subgroup with high relapse risk remains unknown. This study aimed to assess the potential of FPR and AFR in differential diagnosis and risk stratification of early-stage CRC. Methods A discovery (694 and 512 patients with benign colorectal polyps and stage I–II CRC, respectively) and validation (201 benign colorectal polyps cases and 202 stage I–II CRC individuals) cohorts were enrolled in this study. Receiver operating characteristic curve (ROC), Kaplan–Meier curve, and time-dependent ROC were used to evaluate the diagnostic efficacy of AFR and FPR in the two cohorts and overall population, and the discriminating role of FPR in identifying clinical high-relapse risk patients in comparison with common clinical characteristics in stage II CRC patients. Results The area under the curve (AUC) of the preoperative circulating FPR was higher than that of AFR in the diagnosis of stage I–II CRC from colorectal adenomas and benign colorectal polyps in the discovery and validation cohorts and overall population. Carcinoembryonic antigen (CEA) combined with FPR could effectively discriminate early-stage CRC from colorectal adenomas or benign polyps. Preoperative FPR could effectively distinguish stage II subgroups with high and low relapse risk. It was superior to common clinical characteristics in identifying high-risk surgical patients who could benefit from adjuvant chemotherapy (CT) [time-dependent AUC: 0.637 vs. 0.511, p 20 had the highest recurrence (31.16%) and death rates (21.88%), with similar highest recurrence (30.70%) and death (26.82%) rates found in non-CT-treated patients with FPR > 20. Stage II CRC patients with 20 ≥ FPR > 15 could significantly benefit from postoperative CT, as the recurrence (33.30%) and death (35.71%) rates within non-CT treated patients were approximately five times higher than those of the CT-treated cases (6.77% and 7.41% for the recurrence and death rates, respectively). No significant difference in recurrence rate was observed between L-FPR (≤ 15) patients with (10.00%) or without CT (9.76%), indicating that these patients might not require to receive adjuvant CT after curative resection. Conclusions Preoperative FPR combined with CEA is superior to common tumor biomarkers, FPR, or AFR in distinguishing early-stage CRC from benign colorectal polyps. Circulating FPR can be an effective biomarker for identifying high-risk patients and choosing suitable therapeutics for early-stage CRC.

Background and Purpose: Ulcerative colitis (UC) is a refractory inflammatory disease associated with immune dysregulation. Elevated levels of heat shock protein (HSP) 90 in the β but not α subtype were positively associated with disease status in UC patients. This study validated the possibility that pharmacological inhibition or reduction of HSP90β would alleviate colitis, induced by dextran sulfate sodium, in mice and elucidated its mechanisms. Experimental Approach: Histopathological and biochemical analysis assessed disease severity, and bioinformatics and correlation analysis explained the association between the many immune cells and HSP90β. Flow cytometry was used to analyse the homeostasis and transdifferentiation of Th17 and Treg cells. In vitro inhibition and adoptive transfer assays were used to investigate functions of the phenotypically transformed Th17 cells. Metabolomic analysis, DNA methylation detection and chromatin immunoprecipitation were used to explore these mechanisms. Key Results: The selective pharmacological inhibitor (HSP90βi) and shHSP90β significantly mitigated UC in mice and promoted transformation of Th17 to Treg cell phenotype, via Foxp3 transcription. The phenotypically‐transformed Th17 cells by HSP90βi or shHSP90β were able to inhibit lymphocyte proliferation and colitis in mice. HSP90βi and shHSP90β selectively weakened glycolysis by stopping the direct association of HSP90β and GLUT1, the key glucose transporter, to accelerate ubiquitination degradation of GLUT1, and enhance the methylation of Foxp3 CNS2 region. Then, the mediator path was identified as the "lactate‐STAT5‐TET2" cascade. Conclusion and Implications: HSP90β shapes the fate of Th17 cells via glycolysis‐controlled methylation modification to affect UC progression, which provides a new therapeutic target for UC. [ABSTRACT FROM AUTHOR]

This study investigated alterations in functional connectivity (FC) within cortico–basal ganglia–thalamo–cortical (CBTC) circuits and identified critical connections influencing poststroke motor recovery, offering insights into optimizing brain modulation strategies to address the limitations of traditional single‐target stimulation. We delineated individual‐specific parallel loops of CBTC through probabilistic tracking and voxel connectivity profiles‐based segmentation and calculated FC values in poststroke patients and healthy controls, comparing with conventional atlas‐based FC calculation. Support vector machine (SVM) analysis distinguished poststroke patients from controls. Connectome‐based predictive modeling (CPM) used FC values within CBTC circuits to predict upper limb motor function. Poststroke patients exhibited decreased ipsilesional connectivity within the individual‐specific CBTC circuits. SVM analysis achieved 82.8% accuracy, 76.6% sensitivity, and 89.1% specificity using individual‐specific parallel loops. Additionally, CPM featuring positive connections/all connections significantly predicted Fugl‐Meyer assessment of upper extremity scores. There were no significant differences in the group comparisons of conventional atlas‐based FC values, and the FC values resulted in SVM accuracy of 75.0%, sensitivity of 67.2%, and specificity of 82.8%, with no significant CPM capability. Individual‐specific parallel loops show superior predictive power for assessing upper limb motor function in poststroke patients. Precise mapping of the disease‐related circuits is essential for understanding poststroke brain reorganization. [ABSTRACT FROM AUTHOR]

In the face of the huge consumption of fresh water and river sand by the concrete industry and the poor flexural performance of plain concrete, it is theoretically feasible and environmentally friendly to use bamboo fiber as a replacement to reinforce concrete mixed with seawater and sea sand. In this research, taking the volume fraction (0.6%, 1.2%, and 2.4%), aspect ratio (10, 20, and 30) and diameter (1.0, 1.5, and 2.0 mm) of bamboo fibers as parameters, 15 groups of bamboo fiber‐reinforced concrete (BFRC) prisms and one control group of plain seawater sea sand concrete prisms were subjected to four‐point bending test, followed by analyzing the crack pattern, ultimate load, mid‐span deflection and strain. Under the condition of 1.2% volume fraction, 20 aspect ratio, 1.5 mm diameter, and 30 mm length, the maximum increase rate of flexural strength in this research was obtained, and then it was compared with that of flexural strength of concrete prisms reinforced by various natural fibers. In addition, relevant fitting equations and theoretical calculation formulas were derived, laying a foundation for the subsequent research and application of BFRC. [ABSTRACT FROM AUTHOR]

An AND logic gate-based Hg2+ ion colorimetric assay was constructed using the plasmonic and nanozyme dual signal channels of gold nanoparticles (AuNPs). This assay increased the judgment criteria for the identification of Hg2+ ions and effectively improved the accuracy of Hg2+ ion detection. [ABSTRACT FROM AUTHOR]

Silicon-stereogenic chiral organosilanes have found increasing applications in synthetic chemistry, medicinal chemistry, and materials science. In this context, various asymmetric catalytic methods have been established for the diverse synthesis of silicon-stereogenic silanes. In particular, asymmetric organocatalysis is emerging as an important and complementary synthetic tool for the enantioselective construction of silicon-stereocenters, along with the rapid development of chiral-metal catalyzed protocols. Its advent provides a powerful platform to achieve functionalized silicon-stereogenic organosilanes with structural diversity, and should lead to great development in chiral organosilicon chemistry. In this Tutorial Review, we highlight these latest achievements from two aspects: desymmetrizations of prochiral tetraorganosilanes and dynamic kinetic asymmetric transformations of racemic organosilanes by employing five organocatalytic activation modes. The advantages, limitations and synthetic value of each protocol, as well as the synthetic opportunities still open for further exploration, are also discussed. [ABSTRACT FROM AUTHOR]

Soil salinity is a worldwide problem threatening crop yields. Some plant growth‐promoting rhizobacteria (PGPR) could survive in high salt environment and assist plant adaptation to stress. Nevertheless, the genomic and metabolic features, as well as the regulatory mechanisms promoting salt tolerance in plants by these bacteria remain largely unknown. In the current work, a novel halotolerant PGPR strain, namely, Bacillus sp. strain RA can enhance tomato tolerance to salt stress. Comparative genomic analysis of strain RA with its closely related species indicated a high level of evolutionary plasticity exhibited by strain‐specific genes and evolutionary constraints driven by purifying selection, which facilitated its genomic adaptation to salt‐affected soils. The transcriptome further showed that strain RA could tolerate salt stress by balancing energy metabolism via the reprogramming of biosynthetic pathways. Plants exude a plethora of metabolites that can strongly influence plant fitness. The accumulation of myo‐inositol in leaves under salt stress was observed, leading to the promotion of plant growth triggered by Bacillus sp. strain RA. Importantly, myo‐inositol serves as a selective force in the assembly of the phyllosphere microbiome and the recruitment of plant‐beneficial species. It promotes destabilizing properties in phyllosphere bacterial co‐occurrence networks, but not in fungal networks. Furthermore, interdomain interactions between bacteria and fungi were strengthened by myo‐inositol in response to salt stress. This work highlights the genetic adaptation of RA to salt‐affected soils and its ability to impact phyllosphere microorganisms through the adjustment of myo‐inositol metabolites, thereby imparting enduring resistance against salt stress in tomato. [ABSTRACT FROM AUTHOR]

The dilution zone in modern aero-engine combustors is characterized by a strong swirling mainstream with weak transverse jets. This characteristic brings new challenges in homogenizing the temperature distribution at the combustor exit. Therefore, it is imperative to understand the temperature penetration and mixing process of the jet in swirling crossflow (JISCF). This investigation provides new insight in the temperature mixing process for a JISCF in nozzle exit diameter (D) at 7.4, 10.7, and 14 mm and jet to mainstream velocity ratio (VR) from 2.0 to 6.6. The temperature mixing process was measured in a specially designed optical assessable three-dome model gas turbine combustor by planar 1-methylnaphthalene (1-MN) tracer laser-induced fluorescence thermometry. A detailed quantitative measurement of temperature distribution is achieved through the spectral red shift in the fluorescence of 1-MN as the temperature increase. This diagnostic was employed to provide the first two-dimensional temperature distribution for the JISCF. The results showed that the swirling crossflows induce strong spanwise thermal advection, forming secondary low-temperature regions downstream. Generally, the flow structure and mixing process are governed by the interaction of jet and swirling flow. The jet flow parameters, including velocity ratio and diameter, changed the flow structures by changing the interaction between jet and swirling flow. Statistical results and proper orthogonal decomposition (POD) analyses showed a strong anisotropic mixing process in the downstream of the jet. [ABSTRACT FROM AUTHOR]

The longitudinal fluctuating forces of a propeller are a major cause of sound radiation of an underwater vehicle in the low frequency range. A hydraulic leveraged dynamic anti-resonance vibration isolator (HLVI) is proposed to attenuate the longitudinal vibration of a shaft system transmitted to the hull. The semi-analytical model of the shafting system with and without the isolator is set up by employing the frequency response synthesis method, in which the elasticity of the foundation is taken into consideration. Compared to the traditional isolation scheme and DVA, the proposed control scheme will not change the longitudinal effective stiffness and needs a small mass to attenuate the longitudinal vibration of the shafting system. A parametric study was conducted to investigate the key parameters of the isolator and their impact on its isolation performance. An experimental apparatus is set up to validate the isolation scheme. The acceleration frequency response results of the shafting system under axial excitation with both the frequency sweep method and discrete sinusoidal frequencies are presented and discussed. The results indicate that the proposed method is capable of attenuating the corresponding longitudinal vibration of the shafting system. [ABSTRACT FROM AUTHOR]