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Abstract Background Myasthenia gravis (MG) is an autoimmune disease characterized by pathogenic antibodies that target structures of the neuromuscular junction. The evidence suggests that the regulation of long noncoding RNAs (lncRNAs) that is mediated by transcription factors (TFs) plays a key role in the pathophysiology of MG. Nevertheless, the detailed molecular mechanisms of lncRNAs in MG remain largely undetermined. Methods Using microarray analysis, we analyzed the lncRNA levels in MG. By bioinformatics analysis, LINC01566 was found to potentially play an important role in MG. First, qRT‒PCR was performed to verify the LINC1566 expressions in MG patients. Then, fluorescence in situ hybridization was conducted to determine the localization of LINC01566 in CD4 + T cells. Finally, the impact of LINC01566 knockdown or overexpression on CD4 + T-cell function was also analyzed using flow cytometry and CCK-8 assay. A dual-luciferase reporter assay was used to validate the binding of the TF FOSL1 to the LINC01566 promoter. Results Based on the lncRNA microarray and differential expression analyses, we identified 563 differentially expressed (DE) lncRNAs, 450 DE mRNAs and 19 DE TFs in MG. We then constructed a lncRNA-TF-mRNA network. Through network analysis, we found that LINC01566 may play a crucial role in MG by regulating T-cell-related pathways. Further experiments indicated that LINC01566 is expressed at low levels in MG patients. Functionally, LINC01566 is primarily distributed in the nucleus and can facilitate CD4 + T-cell apoptosis and inhibit cell proliferation. Mechanistically, we hypothesized that LINC01566 may negatively regulate the expressions of DUSP3, CCR2, FADD, SIRPB1, LGALS3 and SIRPB1, which are involved in the T-cell activation pathway, to further influence the cellular proliferation and apoptosis in MG. Moreover, we found that the effect of LINC01566 on CD4 + T cells in MG was mediated by the TF FOSL1, and in vitro experiments indicated that FOSL1 can bind to the promoter region of LINC01566. Conclusions In summary, our research revealed the protective roles of LINC01566 in clinical samples and cellular experiments, illustrating the potential roles and mechanism by which FOSL1/LINC01566 negatively regulates CD4 + T-cell activation in MG.

Mood disorders, encompassing major depressive disorder and bipolar disorder, present complex etiologies involving neuroanatomical, neurotransmitter, and inflammatory mechanisms. Recent research explores the role of platelets, traditionally associated with hemostasis, in the pathophysiology of mood disorders. We examine neuroanatomical insights, neurotransmitter dysregulation, and the link between inflammation and mood disorders, emphasizing the complex nature of mood disturbances. Emerging evidence of altered platelet function in mood disorders and the therapeutic potential of antiplatelet agents and serotonin reuptake inhibitors are discussed. While personalized medicine holds promise, further research is needed to fully comprehend this evolving field. This review offers comprehensive insights into mood disorder diagnosis, intervention, and pathophysiology. In this review, a comprehensive literature search was conducted using databases such as PubMed, Scopus, and Web of Science. The search focused on articles published from 2000 to 2023, using keywords like “platelet function,” “mood disorders,” and “neurotransmitter dysregulation.” We included studies that specifically investigated the role of platelets in mood disorders, encompassing various study designs and population demographics.

Ambergris is a very rare and highly valued fauna natural perfume. Its main component, ambrein, undergoes oxidative degradation to produce ambroxide, forming the unique ambergris fragrance. To meet the market demand while not offending the law of protecting sperm whales, ambrein and ambroxide are chemically synthesized. Recently, the biosynthesis of these compounds has been explored as a green and sustainable production route to ensure the safety of use. The ambrein biosynthesis pathway has been successfully constructed in model microorganisms, leading to de novo biosynthesis of ambrein from glucose and glycerol. In addition, partial biosynthesis of ambroxide has been achieved by modular co-culture of engineered sclareol-producing yeast and a natural fungus converting sclareol to ambradiol, which can be further converted to ambroxide by zeolite. Alternatively, ambroxide can be produced by the chemical transformation of biosynthesized farnesene, followed by enzymatic cyclization. In this paper, the efforts toward biosynthesis of ambrein and ambroxide as representative compounds to substitute the natural ambergris are reviewed, and the challenges and prospects are discussed.

BackgroundExtensive malignant-appearing calcifications have traditionally been considered a contraindication for breast-conserving surgery. The evaluation of calcifications largely depends on mammography, which is limited by tissue superimposition and is unable to reveal spatial information about extensive calcifications. Three-dimensional imaging modality is needed to reveal the architecture of extensive calcifications. In the present study, a novel cone-beam breast CT-guided surface location technique was investigated to facilitate breast-conserving surgery in breast cancer patients with extensive malignant breast calcifications.MethodsBiopsy-proved early breast cancer patients with extensive malignant-appearing breast calcifications were included. A patient will be considered suitable for breast-conserving surgery if the spatial segmental distribution of calcifications is found by 3D images of cone-beam breast CT. Then, the margins of the calcifications were located in contrast-enhanced cone-beam breast CT images. Next, skin markers were located using radiopaque materials, and cone-beam breast CT was reperformed to confirm the accuracy of surface location. During breast-conserving surgery, lumpectomy was performed according to the previous surface location, and an intraoperative specimen x-ray was applied to double-check that the entire lesion was removed. Margin assessment was made for both intraoperative frozen section and postoperative pathology examination.ResultsFrom May 2019 to Jun 2022, 11 eligible breast cancer patients in our institution were included. Breast-conserving surgery was performed successfully in all patients using the surface location approach mentioned before. All patients achieved negative margins and satisfied cosmetic results.ConclusionThis study proved the feasibility of cone-beam breast CT-guided surface location for facilitating breast-conserving surgery in breast cancer patients with extensive malignant breast calcifications.

The quality deterioration that is induced by freezing treatment limits the development of frozen dough technology for standardized and delayed baking. In this study, laccase (LAC) and ferulic acid (FA) were employed to improve the rheological properties and microstructure of frozen unfermented dough. The results showed that the dough with LAC + FA had a lower softening degree than the dough with FA alone. Correspondingly, LAC + FA incorporation enhanced the viscoelastic behavior of frozen unfermented dough with better stability. Furthermore, a more uniform and homogeneous gluten network was observed in the LAC + FA-supplemented dough after 21 d of storage. The structural stability of the frozen gluten sample increased after LAC + FA treatment, possibly owing to an increase in the oxidation degree of FA. Moreover, LAC + FA treatment promoted the oxidation of the sulfhydryl groups to some extent, resulting in more extensive cross-linking. LAC + FA treatment hindered the protein conformational changes typically induced by frozen storage compared with LAC alone. Overall, LAC + FA treatment has a synergistic effect on enhancing the viscoelastic behaviors of frozen unfermented dough and inhibiting the conformational variation in frozen gluten; thus, it shows promise for improving frozen dough.

To overcome the tradeoff between strength and ductility of materials and obtain titanium matrix composites with excellent mechanical properties, in this study, the in situ-synthesized TiC particles and Ti-Al-V-Mo-Cr (Ti1400) alloy-reinforced Ti6Al4V (TC4) matrix composites ((Ti1400 + TiC)/TC4) were fabricated by low-energy ball milling and spark plasma sintering. The inhomogeneous distribution of TiC particles and Ti1400 alloy, as well as the compositional and structural transition zone, were characterized. The TiC/TC4 composite displayed a significantly higher yield strength and tensile strength compared to the TC4 alloy. However, the total elongation of the TiC/TC4 composite was only 57% of that in the TC4 alloy. In contrast, the (Ti1400 + TiC)/TC4 composites exhibited noticeably higher total elongation than the TiC/TC4 composite. Furthermore, the tensile strength of the composite increased with the increase in Ti1400 alloy content. The increase in strength can be attributed to solid solution strengthening and fine grain strengthening. The compositional and structural transition zone, formed by element diffusion, provided a better interface combination between the reinforcements and TC4 matrix. In the transition zone and Ti1400 region, a large number of α/β interfaces can effectively alleviate the stress concentration, and the increase in the β phase can bear more plastic deformation, which is conducive to improving the elongation of the composite. As a result, the (Ti1400 + TiC)/TC4 composites exhibited simultaneous improvements in strength and ductility.

Ischemic stroke (IS) is a high-incidence disease that seriously threatens human life and health. Neuroinflammation and immune responses are key players in the pathophysiological processes of IS. However, the underlying immune mechanisms are not fully understood. In this study, we attempted to identify several immune biomarkers associated with IS. We first retrospectively collected validated human IS immune-related genes (IS-IRGs) as seed genes. Afterward, potential IS-IRGs were discovered by applying random walk with restart on the PPI network and the permutation test as a screening strategy. Doing so, the validated and potential sets of IS-IRGs were merged together as an IS-IRG catalog. Two microarray profiles were subsequently used to explore the expression patterns of the IS-IRG catalog, and only IS-IRGs that were differentially expressed between IS patients and controls in both profiles were retained for biomarker selection by the Random Forest rankings. CLEC4D and CD163 were finally identified as immune biomarkers of IS, and a classification model was constructed and verified based on the weights of two biomarkers obtained from the Neural Network algorithm. Furthermore, the CIBERSORT algorithm helped us determine the proportions of circulating immune cells. Correlation analyses between IS immune biomarkers and immune cell proportions demonstrated that CLEC4D was strongly correlated with the proportion of neutrophils (r = 0.72). These results may provide potential targets for further studies on immuno-neuroprotection therapies against reperfusion injury.

In response to the problems of boiler low water level and pump cavitation caused by the leakage of feedwater unloading pipeline in the process of boiler load raising of the conventional steam power system, the relational model of water-lift, mass flow, revs of booster pump, and each impeller of the feedwater pump are identified by using a differential evolution algorithm based on residual correction. The relational model of mass flow and resistance of feedwater pipelines and valves, the calculational model of working fluid parameters in feedwater system, and the performance degradation model of feedwater unloading control valve are established by using be mechanism modeling method. On this basis, the process of boiler load raising is simulated, and the main parameters of feedwater system are obtained at different feedwater unloading flow rates. It is found that the performance degradation of the control valve of the feedwater unloading pipeline is one of the main causes for boiler water low level and pump cavitation in the process of boiler load raising. In order to further clarify the degradation rule of the performance reliability of the feedwater system with the working time, a simulation method integrating the mathematical model and Monte Carlo random sampling is adopted to the performance reliability simulation of a certain type of marine water supply system in the process of boiler load raising. Thus the whole performance reliability changes of this boiler and the performance reliability life of this feedwater unloading control valve are obtained. The research results reveal the mechanism and degeneration rule of a unique fault of the steam power system, which has certain theoretical and engineering application value.

This paper proposes a method to solve the joint optimization of test node selection and fiber thread connection. The problem is modeled as an integer linear programming problem with two classes of decision variables. The first class of decision variables are composed of the number of parallel fiber threads throughout each potential testing route, the other class of decision variables are imposed just to denote whether a node is decided as a location to place testing equipment. The objective of the joint optimization is to minimize the number of nodes where fiber test equipment based on the optical time domain reflectometer are planned to locate. The objective function is just the sum of the second class of decision variables. Two types of linear constraints are needed. The first type of constraints describes the mutual relation between the two classes of variables, and the other type of constraints are formed to depict the impact of the number of fiber threads mounted within each fiber link on the first class of decision variables. Multiple examples are given to exhibit the advantage of joint optimization over heuristic method.

Abstract Background Previous studies have indicated that quantitative MRI (qMR) is beneficial for diagnosis of breast cancer. As a novel qMR technology, synthetic MRI (syMRI) may be advantageous by offering simultaneous generation of T1 and T2 mapping in one scan within a few minutes and without concern to the deposition of the gadolinium contrast agent in cell nucleus. In this study, the potential of quantitative mapping derived from Synthetic MRI (SyMRI) to diagnose breast cancer was investigated. Methods From April 2018 to May 2019, a total of 87 patients with suspicious breast lesions underwent both conventional and SyMRI before treatment. The quantitative metrics derived from SyMRI, including T1 and T2 values, were measured in breast lesions. The diagnostic performance of SyMRI was evaluated with unpaired Student’s t-tests, receiver operating characteristic curve analysis and multivariate logistic regression analysis. The AUCs of quantitative values were compared using Delong test. Results Among 77 patients who met the inclusion criteria, 48 were diagnosed with histopathological confirmed breast cancers, and the rest had benign lesions. The breast cancers showed significantly higher T1 (1611.61 ± 215.88 ms) values and lower T2 (80.93 ± 7.51 ms) values than benign lesions. The area under the ROC curve (AUC) values were 0.931 (95% CI: 0.874–0.989) and 0.883 (95% CI: 0.810–0.956) for T1 and T2 maps, respectively, in diagnostic discrimination between breast cancers and benign lesions. A slightly increased AUC of 0.978 (95% CI: 0.915–0.993) was achieved by combining those two relaxation-based quantitative metrics. Conclusion In conclusion, our preliminary study showed that the quantitative T1 and T2 values obtained by SyMRI could distinguish effectively between benign and malignant breast lesions, and T1 relaxation time showed the highest diagnostic efficiency. Furthermore, combining the two quantitative relaxation metrics further improved their diagnostic performance.

Abstract Background and objectives The diagnostic performance of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in the differential diagnosis of pulmonary tumors remained debatable among published studies. This study aimed to pool and summary the relevant results to provide more robust evidence in this issue using a meta-analysis method. Materials and methods The researches regarding the differential diagnosis of lung lesions using IVIM-DWI were systemically searched in Pubmed, Embase, Web of science and Wangfang database without time limitation. Review Manager 5.3 was used to calculate the standardized mean difference (SMD) and 95% confidence intervals of apparent diffusion coefficient (ADC), tissue diffusivity (D), pseudo-diffusivity (D*), and perfusion fraction (f). Stata 12.0 was used to pool the sensitivity, specificity, and area under the curve (AUC), as well as publication bias and heterogeneity. Fagan’s nomogram was used to predict the post-test probabilities. Results Eleven studies with 481 malignant and 258 benign lung lesions were included. Most include studies showed a low to unclear risk of bias and low concerns regarding applicability. Lung cancer demonstrated a significant lower ADC (SMD = -1.17, P

The feasibility of regenerative cooling technology in scramjet engines has been verified, while the heat transfer behavior involved in the process needs further study. This paper expounds on the necessity of coupled heat-transfer analysis and summarizes its research progress. The results show that the effect of pyrolysis on heat transfer in the cooling channel depends on the heat flux and coking rate, and the coupling relationship between combustion and heat transfer is closely related to the fuel flow rate. Therefore, we confirm that regulating the cooling channel layout according to the real heat-flux distribution, suppressing coking, and accurately controlling the fuel flow rate can contribute to accomplishing the optimal collaborative design of cooling performance and combustion performance. Finally, a conjugate thermal analysis model can be used to evaluate the performance of various thermal protection systems.

Spexin (SPX) is a novel peptide involved in glucose and lipid metabolism and suppresses hepatic total bile acid levels by inhibiting hepatic cholesterol 7α-hydroxylase 1 expression. As important mediators for glycolysis/gluconeogenesis and lipid metabolism, the effects of bile acids on SPX expression is yet to be understood. By using SMMC7721 and BEL-7402 cell lines, we screened the effects of bile acids and found that chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) can stimulate SPX gene transcription. Both CDCA and DCA were able to stimulate SPX mRNA expression in the liver but not colon and ileum in mice. In SMMC7721 and BEL-7402 cells, CDCA- and DCA-induced SPX promoter activity was mimicked by bile acid receptor FXR and TGR5 activation and suppressed by FXR and TGR5 silencing. Adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP) activators significantly increased SPX promoter activity whereas the inhibitors for AC/CAMP/protein kinase A (PKA) and mitogen-activated protein kinases (MAPK) pathway attenuated CDCA- and DCA-induced SPX transcription. Thus, CDCA and DCA stimulate SPX expression at the hepatic level through FXR and TGR5 mediated AC/cAMP/PKA and MAPK cascades.

Ying Zhuge,1,* Huan-Er Ni,1,* Yu-Jie Wang,2 Mu-Ye He,2 Jun-Shan Wang,3 Feng Gao,2,4 Fang Wang1 1Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200800, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, People’s Republic of China; 3Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University, Shanghai 200072, People’s Republic of China; 4Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai 200237, People’s Republic of China *These authors contributed equally to this work Aims: To determine whether use of radiofrequency catheter ablation (RFCA) combined with intravenously administered liposomal doxorubicin (L-DOX) facilitates a reduction in the recovery of post-ablation electrical conduction. Methods: Circumferential ablation was performed on the epicardial surface of the left atrial appendage (LAA) in New Zealand White rabbits, and L-DOX was then administered intravenously. Fluorescence spectrophotometry was used to assess reagent bio-distribution, while Western blots and immunohistochemistry were used to assess the localization of the apoptotic markers Bcl-2, Bax, and cleaved CASP3 in the LAA. Liver, kidney, and cardiac functions were also measured to evaluate the safety of this approach. Results: At 1 week and 1 month after RFCA, a pacing electrocardiogram could not be detected in most of the rabbits that had received the combined RFCA and L-DOX therapy. L-DOX began to target the LAA on the second day after RFCA. L-DOX treatment increased the apoptosis of cardiomyocytes in the regions peripheral to the necrotic area induced by RFCA. Doxorubicin had some effect on liver and kidney function, but these effects were reversible and did not affect survival. Conclusion: The present results provide evidence that L-DOX treatment can reduce the recovery of electrical conduction after RFCA therapy owing to L-DOX-induced apoptosis of cardiomyocytes in the ablated area and the proximal transition zone of the LAA. Keywords: doxorubicin, liposome, radiofrequency catheter ablation, atrial fibrillation, recovered electrical conduction

Objectives: The diagnostic performance of intravoxel incoherent motion diffusion–weighted imaging (IVIM-DWI) in the differential diagnosis of breast tumors remains debatable among published studies. Therefore, this meta-analysis aimed to pool relevant evidence regarding the diagnostic performance of IVIM-DWI in the differential diagnosis of breast tumors.Methods: Studies on the differential diagnosis of breast lesions using IVIM-DWI were systemically searched in the PubMed, Embase and Web of Science databases in recent 10 years. The standardized mean difference (SMD) and 95% confidence intervals of the apparent diffusion coefficient (ADC), tissue diffusivity (D), pseudodiffusivity (D*), and perfusion fraction (f) were calculated using Review Manager 5.3, and Stata 12.0 was used to pool the sensitivity, specificity, and area under the curve (AUC), as well as assess publication bias and heterogeneity. Fagan's nomogram was used to predict the posttest probabilities.Results: Sixteen studies comprising 1,355 malignant and 362 benign breast lesions were included. Most of these studies showed a low to unclear risk of bias and low concerns regarding applicability. Breast cancer had significant lower ADC (SMD = −1.38, P < 0.001) and D values (SMD = −1.50, P < 0.001), and higher f value (SMD = 0.89, P = 0.001) than benign lesions, except D* value (SMD = −0.30, P = 0.20). Invasive ductal carcinoma showed lower ADC (SMD = 1.34, P = 0.01) and D values (SMD = 1.04, P = 0.001) than ductal carcinoma in situ. D value demonstrated the best diagnostic performance (sensitivity = 86%, specificity = 86%, AUC = 0.91) and highest post-test probability (61, 48, 46, and 34% for D, ADC, f, and D* values) in the differential diagnosis of breast tumors, followed by ADC (sensitivity = 76%, specificity = 79%, AUC = 0.85), f (sensitivity = 80%, specificity = 76%, AUC = 0.85) and D* values (sensitivity = 84%, specificity = 59%, AUC = 0.71).Conclusion: IVIM-DWI parameters are adequate and superior to the ADC in the differentiation of breast tumors. ADC and D values can further differentiate invasive ductal carcinoma from ductal carcinoma in situ. IVIM-DWI is also superior in identifying lymph node metastasis, histologic grade, and hormone receptors, and HER2 and Ki-67 status.

Objectives: Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) is a promising non-invasive imaging technique to detect and grade prostate cancer (PCa). However, the results regarding the diagnostic performance of IVIM-DWI in the characterization and classification of PCa have been inconsistent among published studies. This meta-analysis was performed to summarize the diagnostic performance of IVIM-DWI in the differential diagnosis of PCa from non-cancerous tissues and to stratify the tumor Gleason grades in PCa.Materials and Methods: Studies concerning the differential diagnosis of prostate lesions using IVIM-DWI were systemically searched in PubMed, Embase, and Web of Science without time limitation. Review Manager 5.3 was used to calculate the standardized mean difference (SMD) and 95% confidence intervals of the apparent diffusion coefficient (ADC), tissue diffusivity (D), pseudodiffusivity (D*), and perfusion fraction (f). Stata 12.0 was used to pool the sensitivity, specificity, and area under the curve (AUC), as well as publication bias and heterogeneity. Fagan's nomogram was used to predict the post-test probabilities.Results: Twenty studies with 854 patients confirmed with PCa were included. Most of the included studies showed a low to unclear risk of bias and low concerns regarding applicability. PCa showed a significantly lower ADC (SMD = −2.34; P < 0.001) and D values (SMD = −1.86; P < 0.001) and a higher D* value (SMD = 0.29; P = 0.01) than non-cancerous tissues, but no difference was noted with the f value (SMD = −0.16; P = 0.50). Low-grade PCa showed higher ADC (SMD = 0.63; P < 0.001) and D values (SMD = 0.80; P < 0.001) than the high-grade lesions. ADC showed comparable diagnostic performance (sensitivity = 86%; specificity = 86%; AUC = 0.87) but higher post-test probabilities (60, 53, 36, and 36% for ADC, D, D*, and f values, respectively) compared with the D (sensitivity = 82%; specificity = 82%; AUC = 0.85), D* (sensitivity = 70%; specificity = 70%; AUC = 0.75), and f values (sensitivity = 73%; specificity = 68%; AUC = 0.76).Conclusion: IVIM parameters are adequate to differentiate PCa from non-cancerous tissues with good diagnostic performance but are not superior to the ADC value. Diffusion coefficients can further stratify the tumor Gleason grades in PCa.