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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.

Abstract Objectives To evaluate the performance of a dual-energy computed tomography (DECT) virtual non-calcium (VNCa) technique in the detection of edema-like marrow signal intensity (ELMSI) in patients with knee joint osteoarthritis (OA) compared to magnetic resonance imaging (MRI). Methods The study received local ethics board approval, and written informed consent was obtained. DECT and MRI were used to examine 28 knees in 24 patients with OA. VNCa images were generated by dual-energy subtraction of calcium. The knee joint was divided into 15 regions for ELMSI grading, performed independently by two musculoskeletal radiologists, with MRI as the reference standard. We also analyzed CT numbers through receiver operating characteristics and calculated cut-off values. Results For the qualitative analysis, we obtained CT sensitivity (Readers 1, 2 = 83.7%, 89.8%), specificity (Readers 1, 2 = 99.5%, 99.5%), positive predictive value (Readers 1, 2 = 95.3%, 95.7%), and negative predictive value (Readers 1, 2 = 97.9%, 98.7%) for ELMSI. The interobserver agreement was excellent (κ = 0.92). The area under the curve for Reader 1 and Reader 2 was 0.961 (95% CI 0.93, 0.99) and 0.992 (95% CI 0.98, 1.00), respectively. CT numbers obtained from the VNCa images were significantly different between regions with and without ELMSI (p

The changes in the status parameters of the thermal system reflect the operating status of the system in real time. The forecast results of the trend extraction and time series prediction of the current equipment status parameters can be used as a reference for the next operation management strategy and equipment maintenance, which can be used for the long-term system safe and stable operation. In this paper, a method which is described as MWSA, based on the midpoint and regression based empirical mode decomposition (MREMD), the wavelet threshold denoising (WTD) and midpoint and techniques, the singular value decomposition (SVD) and optimized parameter permutation entropy (PE), and an auto regressive integrated moving average model (ARIMA), is applied to the single-parameter time series prediction of thermal systems. First, the MREMD is used to decompose the monitored operating state parameters into a number of intrinsic mode functions (IMF) and residual components. Next, the components that do not meet the screening conditions are subjected to wavelet thresholding. The denoised components and the components that originally meet the filtering conditions are recomposed into new IMF components. Finally, the K-means clustering algorithm based on SVD and PE is used to classify the recomposed IMF components, the component with a lower entropy value is selected and reconstructed into a trend item, and ARIMA is used to predict. An actual case verifies that this method can effectively overcome the interference of high-frequency noise in the original parameter timing, and the prediction accuracy is higher than that of similar methods without noise reduction treatment.

Enhancing the clearance of proteins associated with Alzheimer's disease (AD) emerges as a promising approach for AD therapeutics. This study explores the potential of Radix Stellariae, a traditional Chinese medicine, in treating AD. Utilizing transgenic C. elegans models of AD, we demonstrated that a 75% ethanol extract of Radix Stellariae (RSE) (at 50 µg/mL) effectively diminishes Aβ and Tau protein expression, and alleviates their induced impairments including paralysis, behavioral dysfunction, neurotoxicity, and ROS accumulation. Additionally, RSE enhances the stress resistance of C. elegans. Further investigations revealed that RSE promotes autophagy, a critical cellular process for protein degradation, in these models. We found that inhibiting autophagy-related genes negated the neuroprotective effects of RSE, suggesting a central role for autophagy in the actions of RSE. In PC-12 cells, we observed that RSE not only inhibited Aβ fibril formation but also promoted the degradation of AD-related proteins and reduced their cytotoxicity. Mechanistically, RSE was found to induce autophagy via modulating PI3K/AKT/mTOR and AMPK/mTOR signaling pathways. Importantly, inhibiting autophagy counteracted the beneficial effects of RSE on the clearance of AD-associated proteins. Moreover, we identified Dichotomine B, a β-carboline alkaloid, as a key active constituent of RSE in mitigating AD pathology in C. elegans at concentrations ranging from 50 to 1000 µM. Collectively, our study presents novel discoveries that RSE alleviates AD pathology and toxicity primarily by inducing autophagy, both in vivo and in vitro. These findings open up new avenues for exploring the therapeutic potential of RSE and its active component, Dichotomine B, in treating neurodegenerative diseases like AD.

Acute kidney injury (AKI) is characterized by a rapid decrease in renal function with high mortality and risk of progression to chronic kidney disease (CKD). Ischemia and reperfusion injury (IRI) is one of the major causes of AKI. However, the cellular and molecular responses of the kidney to IRI are complex and not fully understood. Herein, we conducted unbiased proteomics and bioinformatics analyses in an IRI mouse model on days 3, 7, and 21, and validated the results using IRI, unilateral ureteral obstruction (UUO), and biopsies from patients with AKI or CKD. The results indicated an obvious temporal expression profile of differentially expressed proteins and highlighted impaired lipid metabolism during the progression of AKI to CKD. Acyl-coenzyme A oxidase 1 (Acox1), the first rate-limiting enzyme of peroxisomal fatty acid beta-oxidation, was then selected, and its disturbed expression in the two murine models validated the proteomic findings. Accordingly, Acox1 expression was significantly downregulated in renal biopsies from patients with AKI or CKD, and its expression was negatively correlated with kidney injury score. Furthermore, in contrast to the decreased Acox1 expression, lipid droplet accumulation was remarkably increased in these renal tissues, suggesting dysregulation of fatty acid oxidation. In conclusion, our results suggest that defective peroxisomal fatty acid oxidation might be a common pathological feature in the transition from AKI to CKD, and that Acox1 is a promising intervention target for kidney injury and repair.

Pulmonary hypertension (PH) is a progressive, pulmonary vascular disease with high morbidity and mortality. Unfortunately, the pathogenesis of PH is complex and remains unclear. Existing studies have suggested that inflammatory factors are key factors in PH. Interleukin-6 (IL-6) is a multifunctional cytokine that plays a crucial role in the regulation of the immune system. Current studies reveal that IL-6 is elevated in the serum of patients with PH and it is negatively correlated with lung function in those patients. Since IL-6 is one of the most important mediators in the pathogenesis of inflammation in PH, signaling mechanisms targeting IL-6 may become therapeutic targets for this disease. In this review, we detailed the potential role of IL-6 in accelerating PH process and the specific mechanisms and signaling pathways. We also summarized the current drugs targeting these inflammatory pathways to treat PH. We hope that this study will provide a more theoretical basis for targeted treatment in patients with PH in the future.

Cancer remains a formidable challenge in medicine due to its propensity for recurrence and metastasis, which can result in unfavorable treatment outcomes. This challenge is particularly acute for early-stage patients, who may experience recurrence and metastasis without timely detection. Here, we first analyzed the differences in clinical characteristics among the primary tumor, recurrent tumor, and metastatic tumor in different stages of cancer, which may be caused by the molecular level. Moreover, the importance of predicting early cancer recurrence and metastasis is emphasized by survival analyses. Next, we used a multi-omics approach to identify key molecular changes associated with early cancer recurrence and metastasis and discovered that early metastasis in cancer demonstrated a high degree of genomic and cellular heterogeneity. We performed statistical comparisons for each level of omics data including gene expression, mutation, copy number variation, immune cell infiltration, and cell status. Then, various analytical techniques, such as proportional hazard model and Fisher’s exact test, were used to identify specific genes or immune characteristics associated with early cancer recurrence and metastasis. For example, we observed that the overexpression of BPIFB1 and high initial B-cell infiltration levels are linked to early cancer recurrence, while the overexpression or amplification of ANKRD22 and LIPM, mutation of IGHA1 and MUC16, high fibroblast infiltration level, M1 polarization of macrophages, cellular status of DNA repair are all linked to early cancer metastasis. These findings have led us to construct classifiers, and the average area under the curve (AUC) of these classifiers was greater than 0.75 in The Cancer Genome Atlas (TCGA) cancer patients, confirming that the features we identified could be biomarkers for predicting recurrence and metastasis of early cancer. Finally, we identified specific early sensitive targets for targeted therapy and immune checkpoint inhibitor therapy. Once the biomarkers we identified changed, treatment-sensitive targets can be treated accordingly. Our study has comprehensively characterized the multi-omics characteristics and identified a panel of biomarkers of early cancer recurrence and metastasis. Overall, it provides a valuable resource for cancer recurrence and metastasis research and improves our understanding of the underlying mechanisms driving early cancer recurrence and metastasis.

Purpose: We retrospectively compared the diagnostic performance of contrast-enhanced ultrasonography (CEUS) and contrast-enhanced computer tomography–magnetic resonance imaging (CT/MRI) for recurrent hepatocellular carcinoma (HCC) after curative treatment. Materials and methods: After curative treatment with 421 ultrasound (US) detected lesions, 303 HCC patients underwent both CEUS and CT/MRI. Each lesion was assigned a Liver Imaging Reporting and Data System (LI-RADS) category according to CEUS and CT/MRI LI-RADS. Receiver-operating characteristic (ROC) curves were computed to determine the optimal diagnosis algorithms for CEUS, CT and MRI. The diagnostic accuracy, sensitivity, specificity, and area under the curve (AUC) were compared between CEUS and CT/MRI. Results: Among the 421 lesions, 218 were diagnosed as recurrent HCC, whereas 203 lesions were diagnosed as benign. In recurrent HCC, CEUS detected more arterial hyperenhancement (APHE) and washout than CT and more APHE than MRI. CEUS yielded better diagnostic performance than CT (AUC: 0.981 vs. 0.958) (p = 0.024) comparable diagnostic performance to MRI (AUC: 0.952 vs. 0.933) (p > 0.05) when using their optimal diagnostic criteria. CEUS missed 12 recurrent HCCs, CT missed one, and MRI missed none. The detection rate of recurrent HCC on CEUS (94.8%, 218/230) was lower than that on CT/MRI (99.6%, 259/260) (p = 0.001). Lesions located on the US blind spots and visualization score C would hinder the ability of CEUS to detect recurrent HCC. Conclusion: CEUS demonstrated excellent diagnostic performance but an inferior detection rate for recurrent HCC. CEUS and CT/MRI played a complementary role in the detection and characterization of recurrent HCC.

Alzheimer’s disease (AD) presents a significant challenge to global healthcare systems, with current treatments offering only modest relief and often bringing unwanted side effects, necessitating the exploration of more effective and safer drugs. In this study, we employed the Caenorhabditis elegans (C. elegans) model, specifically the AD-like CL4176 strain expressing the human Aβ(1–42) protein, to investigate the potential of Reineckia carnea extract and its fractions. Our results showed that the Reineckia carnea ether fraction (REF) notably diminished the paralysis rates of CL4176 worms. Additionally, REF also attenuated the neurotoxicity effects prompted by Tau proteins in the BR5270 worms. Moreover, REF was observed to counteract the accumulation of Aβ and pTau proteins and their induced oxidative stress in C. elegans AD-like models. Mechanistic studies revealed that REF’s benefits were associated with the induction of autophagy in worms; however, these protective effects were nullified when autophagy-related genes were suppressed using RNAi bacteria. Together, these findings highlight Reineckia carnea ether fraction as a promising candidate for AD treatment, warranting further investigation into its autophagy-inducing components and their molecular mechanisms.

Abstract Apoptotic resistance leads to persistent accumulation of senescent cells and sustained expression of a senescence-associated secretory phenotype, playing an essential role in the progression of tissue fibrosis. However, whether senescent renal tubular epithelial cells (RTECs) exhibit an apoptosis-resistant phenotype, and the role of this phenotype in diabetic nephropathy (DN) remain unclear. Our previous study was the first to demonstrate that decoy receptor 2 (DcR2) is associated with apoptotic resistance in senescent RTECs and renal fibrosis. In this study, we aimed to further explore the mechanism of DcR2 in apoptosis-resistant RTECs and renal fibrosis in DN. DcR2 was co-localized with fibrotic markers (α-SMA, collagen IV, fibronectin), senescent marker p16, and antiapoptotic proteins FLIP and Bcl2 but rarely co-localized with caspase 3 or TUNEL. DcR2 overexpression promoted renal fibrosis in mice with streptozotocin (STZ)-induced DN, as evidenced by augmented Masson staining and upregulated expression of fibrotic markers. DcR2 overexpression also enhanced FLIP expression while reducing the expression of pro-apoptotic proteins (caspases 8 and 3) in senescent RTECs, resulting in apoptotic resistance. In contrast, DcR2 knockdown produced the opposite effects in vitro and in vivo. Moreover, quantitative proteomics and co-immunoprecipitation experiments demonstrated that DcR2 interacted with glucose-related protein 78 kDa (GRP78), which has been shown to promote apoptotic resistance in cancer. GRP78 exhibited co-localization with senescent and antiapoptotic markers but was rarely co-expressed with caspase 3 or TUNEL. Additionally, GRP78 knockdown decreased the apoptosis resistance of HG-induced senescent RTECs with upregulated cleaved caspase 3 and increased the percentage of apoptotic RTECs. Mechanistically, DcR2 mediated apoptotic resistance in senescent RTECs by enhancing GRP78–caspase 7 interactions and promoting Akt phosphorylation. Thus, DcR2 mediated the apoptotic resistance of senescent RTECs and renal fibrosis by interacting with GRP78, indicating that targeting the DcR2–GRP78 axis represents a promising therapeutic strategy for DN.

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.

Aimed at the lack of effective stability evaluation methods for the current steam power system, an operation stability assessment method suitable for single parameter is proposed. This method is a composite method, which first applied the midpoint and regression based empirical mode decomposition (MREMD) and singular value decomposition (SVD) to decompose the time series of operation parameters and extract their hidden trend terms. Then, the components are selected for reconstruction according to the optimal algorithm parameter permutation entropy (OAPPE) of each component. Finally, the auto-regressive integrated moving average (ARIMA ) model commonly used in the non-stationary time series analysis is utilized to predict the trend and the disturbance of parameters, and their distribution characteristics are also extracted in this process, based on which, the probability of instability (PI) of operation parameters at each point on the predicted trend are calculated, and their stabilities are quantitatively evaluated. The actual case proves that this method can effectively assess the operation stability of a single parameter of the steam power system, which has a certain theoretical innovation and engineering application value.