Serplulimab combined with gemcitabine, nab-paclitaxel and stereotactic body radiotherapy as the first-line treatment for patients with metastatic pancreatic adenocarcinoma in China: a multicentre, single-arm, phase II trial (ICSBR) protocol.

INTRODUCTION: Patients with pancreatic ductal adenocarcinoma (PDAC) remain a poor prognosis despite the development of chemotherapy. Although programmed cell death 1 (PD-1) blockade has shown great efficacy in various solid tumours, its application in treating PDAC is limited. Recent studies have indicated that chemotherapy or stereotactic body radiotherapy (SBRT) may improve the antitumour effect of PD-1 blockade in patients with PDAC. The objective of this study is to evaluate the efficacy and safety of combined therapy comprising PD-1 blockade, gemcitabine plus nab-paclitaxel chemotherapy and SBRT for patients with metastatic PDAC. METHODS AND ANALYSIS: This is a multicentre, single-arm, prospective phase II clinical trial. Forty-three patients diagnosed with metastatic PDAC will be enrolled. The eligible patients will be intravenously administered 1000 mg/m2 gemcitabine and 125 mg/m2 nab-paclitaxel on days 1 and 8 of the 21-day cycle. Serplulimab (200 mg) will be administered intravenously on day 1 of the 21-day cycle. Furthermore, during the second cycle, the patients will undergo SBRT with doses of 33 Gy in five fractions for primary lesions or doses of 24 Gy in three fractions for metastases. The primary endpoint is the 6-month progression-free survival (PFS) rate. The secondary endpoints overall survival, PFS, overall response rate, disease control rate, time to progression, duration of response, duration of disease control and safety. Moreover, this trial seeks to investigate biomarkers such as circulating tumour DNA and circulating hybrid cells in patients diagnosed with metastatic PDAC. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee on Biomedical Research, West China Hospital of Sichuan University. The study results will be presented at international conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2300073237.

Liguzinediol potentiates the metabolic remodeling by activating the AMPK/SIRT3 pathway and represses Caspase-3/GSDME-mediated pyroptosis to ameliorate cardiotoxicity.

BACKGROUND: Liguzinediol (Lig) has emerged as a promising candidate for mitigating Doxorubicin (DOX)-induced cardiotoxicity, a significant limitation in the clinical application of this widely used antineoplastic drug known for its efficacy. This study aimed to explore the effects and potential mechanisms underlying Lig's protective role against DOX-induced cardiotoxicity. METHODS: C57BL/6 mice were treated with DOX. Cardiac function changes were observed by echocardiography. Cardiac structure changes were observed by HE and Masson staining. Immunofluorescence was applied to visualize the cardiomyocyte apoptosis. Western blotting was used to detect the expression levels of AMP-activated protein kinase (AMPK), sirtuin 3 (SIRT3), Caspase-3 and gasdermin E N-terminal fragment (GSDME-N). These experiments confirmed that Lig had an ameliorative effect on DOX-induced cardiotoxicity in mice. RESULTS: The results demonstrated that Lig effectively countered myocardial oxidative stress by modulating intracellular levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Lig reduced levels of creatine kinase (CK) and lactate dehydrogenase (LDH), while ameliorating histopathological changes and improving electrocardiogram profiles in vivo. Furthermore, the study revealed that Lig activated the AMPK/SIRT3 pathway, thereby enhancing mitochondrial function and attenuating myocardial cell apoptosis. In experiments with H9C2 cells treated with DOX, co-administration of the AMPK inhibitor compound C (CC) led to a significant increase in intracellular ROS levels. Lig intervention reversed these effects, along with the downregulation of GSDME-N, interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), suggesting a potential role of Lig in mitigating Caspase-3/GSDME-mediated pyroptosis. CONCLUSION: The findings of this study suggest that Lig effectively alleviates DOX-induced cardiotoxicity through the activation of the AMPK/SIRT3 pathway, thereby presenting itself as a natural product with therapeutic potential for preventing DOX-associated cardiotoxicity. This novel approach may pave the way for the development of alternative strategies in the clinical management of DOX-induced cardiac complications.

Type X collagen knockdown inactivate ITGB1/PI3K/AKT to suppress chronic unpredictable mild stress-stimulated triple-negative breast cancer progression.

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer, has a poor prognosis and limited access to efficient targeted treatments. Chronic unpredictable mild stress (CUMS) is highly risk factor for TNBC occurrence and development. Type X collagen (COL10A1), a crucial protein component of the extracellular matrix, ranks second among all aberrantly expressed genes in TNBC, and it is significantly up-regulated under CUMS. Nevertheless, the impact of CUMS and COL10A1 on TNBC, along with the underlying mechanisms are still unclear. In this research, we studied the effect of CUMS-induced norepinephrine (NE) elevation on TNBC, and uncovered that it notably enhanced TNBC cell proliferation, migration, and invasion in vitro, and also fostering tumor growth and lung metastasis in vivo. Additionally, our investigation found that COL10A1 directly interacted with integrin subunit beta 1 (ITGB1), then activates the downstream PI3K/AKT signaling pathway, thereby promoting TNBC growth and metastasis, while it was reversed by knocking down of COL10A1 or ITGB1. Our study demonstrated that the TNBC could respond to CUMS, and advocate for COL10A1 as a pivotal therapeutic target in TNBC treatment.

Is decreasing problematic mobile phone use a pathway for alleviating adolescent depression and sleep disorders? A randomized controlled trial testing the effectiveness of an eight-session mindfulness-based intervention.

Objective: The present study aimed to evaluate the efficacy of a mindfulness-based cognitive therapy (MBCT) intervention in reducing problematic mobile phone use, depression, and sleep disorders among adolescents. Additionally, it sought to investigate whether the decrease in problematic mobile phone use acted as a mediator in the relationship between the MBCT intervention and adolescent depression and sleep disorders. Methods: In a randomized controlled trial, a total of 104 adolescents were randomly assigned to the mindfulness group (n = 52) or the wait-list control group (n = 52). The mindfulness group students completed eight 45-min sessions of mindfulness training in four weeks. The outcomes were measured at baseline, postintervention, and at the 2-month follow-up. Results: Compared with the control group, the mindfulness group had significantly greater levels of mindfulness and lower levels of problematic mobile phone use, depression, and sleep disorders postintervention. The intervention effects were maintained at the 2-month follow-up. In addition, decreased problematic mobile phone use significantly mediated the association between the MBCT intervention and decreased depression and decreased sleep disorders. Conclusion: The findings suggest that MBCT could improve adolescent depression and sleep disorders and that decreasing problematic mobile phone use is an effective pathway accounting for the MBCT intervention effect on adolescent depression and sleep disorders.

Systematic simulation of tumor cell invasion and migration in response to time-varying rotating magnetic field.

Cancer invasion and migration play a pivotal role in tumor malignancy, which is a major cause of most cancer deaths. Rotating magnetic field (RMF), one of the typical dynamic magnetic fields, can exert substantial mechanical influence on cells. However, studying the effects of RMF on cell is challenging due to its complex parameters, such as variation of magnetic field intensity and direction. Here, we developed a systematic simulation method to explore the influence of RMF on tumor invasion and migration, including a finite element method (FEM) model and a cell-based hybrid numerical model. Coupling with the data of magnetic field from FEM, the cell-based hybrid numerical model was established to simulate the tumor cell invasion and migration. This model employed partial differential equations (PDEs) and finite difference method to depict cellular activities and solve these equations in a discrete system. PDEs were used to depict cell activities, and finite difference method was used to solve the equations in discrete system. As a result, this study provides valuable insights into the potential applications of RMF in tumor treatment, and a series of in vitro experiments were performed to verify the simulation results, demonstrating the model's reliability and its capacity to predict experimental outcomes and identify pertinent factors. Furthermore, these findings shed new light on the mechanical and chemical interplay between cells and the ECM, offering new insights and providing a novel foundation for both experimental and theoretical advancements in tumor treatment by using RMF.

Potential targets for the treatment of MI: GRP75-mediated Ca2+ transfer in MAM.

After myocardial infarction (MI), there is a notable disruption in cellular calcium ion homeostasis and mitochondrial function, which is believed to be intricately linked to endoplasmic reticulum (ER) stress. This research endeavors to elucidate the involvement of glucose regulated protein 75 (GRP75) in post-MI calcium ion homeostasis and mitochondrial function. In MI rats, symptoms of myocardial injury were accompanied by an increase in the activation of ER stress. Moreover, in oxygen-glucose deprivation (OGD)-induced cardiomyocytes, it was confirmed that inhibiting ER stress exacerbated intracellular Ca2+ disruption and cell apoptosis. Concurrently, the co-localization of GRP75 with IP3R and VDAC1 increased under ER stress in cardiomyocytes. In OGD-induced cardiomyocytes, knockdown of GRP75 not only reduced the Ca2+ levels in both the ER and mitochondria and improved the ultrastructure of cardiomyocytes, but it also increased the number of contact points between the ER and mitochondria, reducing mitochondria associated endoplasmic reticulum membrane (MAM) formation, and decreased cell apoptosis. Significantly, knockdown of GRP75 did not affect the protein expression of PERK and hypoxia-inducible factor 1α (HIF-1α). Transcriptome analysis of cardiomyocytes revealed that knockdown of GRP75 mainly influenced the molecular functions of sialyltransferase and IP3R, as well as the biosynthesis of glycosphingolipids and lactate metabolism. The complex interaction between the ER and mitochondria, driven by the GRP75 and its associated IP3R1-GRP75-VDAC1 complex, is crucial for calcium homeostasis and cardiomyocyte's adaptive response to ER stress. Modulating GRP75 could offer a strategy to regulate calcium dynamics, diminish glycolysis, and thereby mitigate cardiomyocyte apoptosis.

Correction: MiR-4458-loaded gelatin nanospheres target COL11A1 for DDR2/SRC signaling pathway inactivation to suppress the progression of estrogen receptor-positive breast cancer.

Correction for 'MiR-4458-loaded gelatin nanospheres target COL11A1 for DDR2/SRC signaling pathway inactivation to suppress the progression of estrogen receptor-positive breast cancer' by Jie Liu et al., Biomater. Sci., 2022, 10, 4596-4611, https://doi.org/10.1039/D2BM00543C.

Gradient Rotating Magnetic Fields Impairing F-Actin-Related Gene CCDC150 to Inhibit Triple-Negative Breast Cancer Metastasis by Inactivating TGF-ß1/SMAD3 Signaling Pathway.

Triple-negative breast cancer (TNBC) is the most aggressive and lethal malignancy in women, with a lack of effective targeted drugs and treatment techniques. Gradient rotating magnetic field (RMF) is a new technology used in oncology physiotherapy, showing promising clinical applications due to its satisfactory biosafety and the abundant mechanical force stimuli it provides. However, its antitumor effects and underlying molecular mechanisms are not yet clear. We designed two sets of gradient RMF devices for cell culture and animal handling. Gradient RMF exposure had a notable impact on the F-actin arrangement of MDA-MB-231, BT-549, and MDA-MB-468 cells, inhibiting cell migration and invasion. A potential cytoskeleton F-actin-associated gene, CCDC150, was found to be enriched in clinical TNBC tumors and cells. CCDC150 negatively correlated with the overall survival rate of TNBC patients. CCDC150 promoted TNBC migration and invasion via activation of the transforming growth factor ß1 (TGF-ß1)/SMAD3 signaling pathway in vitro and in vivo. CCDC150 was also identified as a magnetic field response gene, and it was marked down-regulated after gradient RMF exposure. CCDC150 silencing and gradient RMF exposure both suppressed TNBC tumor growth and liver metastasis. Therefore, gradient RMF exposure may be an effective TNBC treatment, and CCDC150 may emerge as a potential target for TNBC therapy.

Accurate leukocyte detection based on deformable-DETR and multi-level feature fusion for aiding diagnosis of blood diseases.

In standard hospital blood tests, the traditional process requires doctors to manually isolate leukocytes from microscopic images of patients' blood using microscopes. These isolated leukocytes are then categorized via automatic leukocyte classifiers to determine the proportion and volume of different types of leukocytes present in the blood samples, aiding disease diagnosis. This methodology is not only time-consuming and labor-intensive, but it also has a high propensity for errors due to factors such as image quality and environmental conditions, which could potentially lead to incorrect subsequent classifications and misdiagnosis. Contemporary leukocyte detection methods exhibit limitations in dealing with images with fewer leukocyte features and the disparity in scale among different leukocytes, leading to unsatisfactory results in most instances. To address these issues, this paper proposes an innovative method of leukocyte detection: the Multi-level Feature Fusion and Deformable Self-attention DETR (MFDS-DETR). To tackle the issue of leukocyte scale disparity, we designed the High-level Screening-feature Fusion Pyramid (HS-FPN), enabling multi-level fusion. This model uses high-level features as weights to filter low-level feature information via a channel attention module and then merges the screened information with the high-level features, thus enhancing the model's feature expression capability. Further, we address the issue of leukocyte feature scarcity by incorporating a multi-scale deformable self-attention module in the encoder and using the self-attention and cross-deformable attention mechanisms in the decoder, which aids in the extraction of the global features of the leukocyte feature maps. The effectiveness, superiority, and generalizability of the proposed MFDS-DETR method are confirmed through comparisons with other cutting-edge leukocyte detection models using the private WBCDD, public LISC and BCCD datasets. Our source code and private WBCCD dataset are available at https://github.com/JustlfC03/MFDS-DETR.

A chitosan-based conductive double network hydrogel doped by tannic acid-reduced graphene oxide with excellent stretchability and high sensitivity for wearable strain sensors.

Conductive hydrogels usually suffer from weak mechanical properties and are easily destroyed, resulting in limited applications in flexible electronics. Concurrently, adding conductive additives to the hydrogel solution increases the probability of agglomeration and uneven dispersion issues. In this study, the biocompatible natural polymer chitosan was used as the network substrate. The rigid network employed was the Cit3-ion crosslinked chitosan (CS) network, and the MBA chemically crosslinked polyacrylamide (PAM) network was used as the flexible network. Tannic acid-reduced graphene oxide (TA-rGO), which has excellent conductivity and dispersibility, is used as a conductive filler. Thus, a CS/TA-rGO/PAM double network conductive hydrogel with excellent performance, high toughness, high conductivity, and superior sensing sensitivity was prepared. The prepared CS/TA-rGO/PAM double network conductive hydrogels have strong tensile properties (strain and toughness as high as 2009 % and 1045 kJ/cm3), excellent sensing sensitivity (GF value was 4.01), a wider strain detection range, high cycling stability and durability, good biocompatibility, and antimicrobial properties. The hydrogel can be assembled into flexible wearable devices that can not only dynamically detect human movements, such as joint bending, facial expression changes, swallowing, and saying, but also recognize handwriting and enable human-computer interaction.

Attenuation of estrogen and its receptors in the post-menopausal stage exacerbates dyslipidemia and leads to cognitive impairment.

Cognitive dysfunction increases as menopause progresses. We previously found that estrogen receptors (ERs) contribute to dyslipidemia, but the specific relationship between ERs, dyslipidemia and cognitive dysfunction remains poorly understood. In the present study, we analyzed sequencing data from female hippocampus and normal breast aspirate samples from normal and Alzheimer's disease (AD) women, and the results suggest that abnormal ERs signaling is associated with dyslipidemia and cognitive dysfunction. We replicated a mouse model of dyslipidemia and postmenopausal status in LDLR-/- mice and treated them with ß-estradiol or simvastatin, and found that ovariectomy in LDLR-/- mice led to an exacerbation of dyslipidemia and increased hippocampal apoptosis and cognitive impairment, which were associated with reduced estradiol levels and ERα, ERß and GPER expression. In vitro, a lipid overload model of SH-SY-5Y cells was established and treated with inhibitors of ERs. ß-estradiol or simvastatin effectively attenuated dyslipidemia-induced neuronal apoptosis via upregulation of ERs, whereas ERα, ERß and GPER inhibitors together abolished the protective effect of simvastatin on lipid-induced neuronal apoptosis. We conclude that decreased estrogen and its receptor function in the postmenopausal stage promote neuronal damage and cognitive impairment by exacerbating dyslipidemia, and that estrogen supplementation or lipid lowering is an effective way to ameliorate hippocampal damage and cognitive dysfunction via upregulation of ERs.

The Association between Perceived Family Financial Stress and Adolescent Suicide Ideation: A Moderated Mediation Model.

Nowadays, suicide (especially adolescents' suicide) has been an increasingly prominent social problem worldwide; suicide ideation, as an important predictor, has been the focus of relevant studies and practices. Against this background, the present study aimed to examine the association between perceived family financial stress and adolescents' suicidal ideation, as well as the potential roles of depression and parent-child attachment. A sample of 526 junior middle school students was recruited voluntarily to participate in this cross-sectional study, and the results indicated that the prevalence of suicidal ideation among junior high school students was 15.45%; perceived family financial stress was positively associated with suicidal ideation, and depression could significantly mediate this relation; parent-child attachment significantly moderated the mediating effect of depression (in particular, the relation between depression and suicidal ideation); specifically, this relation was stronger among adolescents with lower values of parent-child attachment. These findings could deepen our understanding of the influences of perceived family financial condition and the risky factors of adolescents' suicidal ideation, which could provide guidance for the prevention and intervention of adolescents' depression and suicidal ideation.

Recent progress of mechanosensitive mechanism on breast cancer.

The mechanical environment is important for tumorigenesis and progression. Tumor cells can sense mechanical signals by mechanosensitive receptors, and these mechanical signals can be converted to biochemical signals to regulate cell behaviors, such as cell differentiation, proliferation, migration, apoptosis, and drug resistance. Here, we summarized the effects of the mechanical microenvironment on breast cancer cell activity, and mechanotransduction mechanism from cellular microenvironment to cell membrane, and finally to the nucleus, and also relative mechanosensitive proteins, ion channels, and signaling pathways were elaborated, therefore the mechanical signal could be transduced to biochemical or molecular signal. Meanwhile, the mechanical models commonly used for biomechanics study in vitro and some quantitative descriptions were listed. It provided an essential theoretical basis for the occurrence and development of mechanosensitive breast cancer, and also some potential drug targets were proposed to treat such disease.

Recent progress on the effect of extracellular matrix on occurrence and progression of breast cancer.

Breast cancer (BC) metastasis is an enormous challenge targeting BC therapy. The extracellular matrix (ECM), the principal component of the BC metastasis niche, is the pivotal driver of breast tumor development, whose biochemical and biophysical characteristics have attracted widespread attention. Here, we review the biological effects of ECM constituents and the influence of ECM stiffness on BC metastasis and drug resistance. We provide an overview of the relative signal transduction mechanisms, existing metastasis models, and targeted drug strategies centered around ECM stiffness. It will shed light on exploring more underlying targets and developing specific drugs aimed at ECM utilizing biomimetic platforms, which are promising for breast cancer treatment.

CL4-modified exosomes deliver lncRNA DARS-AS1 siRNA to suppress triple-negative breast cancer progression and attenuate doxorubicin resistance by inhibiting autophagy.

Triple-negative breast cancer (TNBC) is a fatal disease. Drug resistance and the lack of effective drugs are the leading causes of death in patients with TNBC. Recently, long non-coding RNAs have been proven to be effective drug design targets owing to their high tissue specificity; however, an effective drug delivery system is necessary for their clinical application. In this study, we constructed a novel nanodrug delivery system based on the epidermal growth factor receptor (EGFR)-targeted aptamer CL4-modified exosomes (EXOs-CL4) for the targeted delivery of aspartyl-tRNA synthetase-antisense RNA 1 (DARS-AS1) small interfering RNA (siRNA) and doxorubicin (DOX) to TNBC cells in vitro and in vivo. This delivery system exerted potent anti-proliferation, anti-migration, and pro-apoptotic effects on TNBC cells. Silencing DARS-AS1 increased the sensitivity of TNBC cells to DOX by suppressing the transforming growth factor-ß (TGF-ß)/Smad3 signaling pathway-induced autophagy, thereby enhancing the synergetic antitumor effects. Collectively, our findings revealed that EXOs-CL4-mediated delivery of DARS-AS1 siRNA can be used as a new treatment strategy for DOX-resistant TNBC. Moreover, EXOs-CL4 can be used as effective drug delivery systems for targeted TNBC therapy.

MtESN2 is a subgroup II sulphate transporter required for symbiotic nitrogen fixation and prevention of nodule early senescence in Medicago truncatula.

Adequate distribution of mineral sulphur (S) nutrition to nodules mediated by sulphate transporters is crucial for nitrogen fixation in symbiosis establishment process. However, the molecular mechanisms underlying this process remain largely unknown. In this study, we characterized the function of Early Senescent Nodule 2 (MtESN2), a gene crucial to nitrogen fixation in Medicago truncatula. Mutations in MtESN2 resulted in severe developmental and functional defects including dwarf shoots, early senescent nodules, and lower nitrogenase activity under symbiotic conditions compared to wild-type plants. MtESN2 encodes an M. truncatula sulphate transporter that is expressed only in roots and nodules, with the highest expression levels in the transition zone and nitrogen-fixing zone of nodules. MtESN2 exhibited sulphate transport activity when expressed in yeast. Immunolocalization analysis showed that MtESN2-yellow fluorescent protein fusion protein was localized to the plasma membranes of both uninfected and infected cells of nodules, where it might transport sulphate into both rhizobia-infected and uninfected cells within the nodules. Our results reveal an unreported sulphate transporter that contributes to effective symbiosis and prevents nodule early senescence in M. truncatula.

Nodule-specific cysteine-rich peptide 343 is required for symbiotic nitrogen fixation in Medicago truncatula.

Symbiotic interactions between legumes and rhizobia lead to the development of root nodules and nitrogen fixation by differentiated bacteroids within nodules. Differentiation of the endosymbionts is reversible or terminal, determined by plant effectors. In inverted repeat lacking clade legumes, nodule-specific cysteine-rich (NCR) peptides control the terminal differentiation of bacteroids. Medicago truncatula contains ∼700 NCR-coding genes. However, the role of few NCR peptides has been demonstrated. Here, we report characterization of fast neutron 2106 (FN2106), a symbiotic nitrogen fixation defective (fix-) mutant of M. truncatula. Using a transcript-based approach, together with linkage and complementation tests, we showed that loss-of-function of NCR343 results in impaired bacteroid differentiation and/or maintenance and premature nodule senescence of the FN2106 mutant. NCR343 was specifically expressed in nodules. Subcellular localization studies showed that the functional NCR343-YFP fusion protein colocalizes with bacteroids in symbiosomes in infected nodule cells. Transcriptomic analyses identified senescence-, but not defense-related genes, as being significantly upregulated in ncr343 (FN2106) nodules. Taken together, results from our phenotypic and transcriptomic analyses of a loss-of-function ncr343 mutant demonstrate an essential role of NCR343 in bacteroid differentiation and/or maintenance required for symbiotic nitrogen fixation.

Ligustrazine alleviates pulmonary arterial hypertension in rats by promoting the formation of myocardin transcription complex in the nucleus of pulmonary artery smooth muscle cells.

Pulmonary arterial hypertension (PAH) is a pathophysiological state of abnormally elevated pulmonary arterial pressure caused by drugs, inflammation, toxins, viruses, hypoxia, and other risk factors. We studied the therapeutic effect and target of tetramethylpyrazine (tetramethylpyrazine [TMP]; ligustrazine) in the treatment of PAH and we speculated that dramatic changes in myocardin levels can significantly affect the progression of PAH. In vivo, the results showed that administration of TMP significantly prolonged the survival of PAH rats by reducing the proliferative lesions, right ventricular systolic pressure (RVSP), mean pulmonary arterial pressure (mPAP), and the Fulton index in the heart and lung of PAH rats. In vitro, TMP can regulate the levels of smooth muscle protein 22-alpha (SM22-α), and myocardin as well as intracellular cytokines such as NO, transforming growth factor beta (TGF-ß), and connective tissue growth factor (CTGF) in a dose-dependent manner (25, 50, or 100 µM). Transfection of myocardin small interfering RNA (siRNA) aggravated the proliferation of pulmonary artery smooth muscle cells (PSMCs), and the regulatory effect of TMP on α-smooth muscle actin (α-SMA) and osteopontin (OPN) disappeared. The application of 10 nM estrogen receptor alpha (ERα) inhibitor MPP promoted the proliferation of PSMCs, but it does not affect the inhibition of TMP on PSMCs proliferation. Finally, we found that TMP promoted the nucleation of myocardin-related transcription factor-A (MRTF-A) and combined it with myocardin. In conclusion, TMP can inhibit the transformation of PSMCs from the contractile phenotype to the proliferative phenotype by promoting the formation of the nuclear (MRTF-A/myocardin) transcription complex to treat PAH.

The effect of magnetic fields on tumor occurrence and progression: Recent advances.

Malignancies are the leading human health threat worldwide. Despite rapidly developing treatments, poor prognosis and outcome are still common. Magnetic fields have shown good anti-tumoral effects both in vitro and in vivo, and represent a potential non-invasive treatment; however, the specific underlying molecular mechanisms remain unclear. We here review recent studies on magnetic fields and their effect on tumors at three different levels: organismal, cellular, and molecular. At the organismal level, magnetic fields suppress tumor angiogenesis, microcirculation, and enhance the immune response. At the cellular level, magnetic fields affect tumor cell growth and biological functions by affecting cell morphology, cell membrane structure, cell cycle, and mitochondrial function. At the molecular level, magnetic fields suppress tumors by interfering with DNA synthesis, reactive oxygen species level, second messenger molecule delivery, and orientation of epidermal growth factor receptors. At present, scientific experimental evidence is still lacking; therefore, systematic studies on the biological mechanisms involved are urgently needed for the future application of magnetic fields to tumor treatment.

Aperiodic neural activity reflects metacontrol.

Higher-level cognitive functions are mediated via complex oscillatory activity patterns and its analysis is dominating cognitive neuroscience research. However, besides oscillatory (period) activity, also aperiodic activity constitutes neural dynamics, but its relevance for higher-level cognitive functions is only beginning to be understood. The present study examined whether the broadband EEG aperiodic activity reflects principles of metacontrol. Metacontrol conceptualizes whether it is more useful to engage in more flexible processing of incoming information or to shield cognitive processes from incoming information (persistence-heavy processing). We examined EEG and behavioral data from a sample of n = 191 healthy participants performing a Simon Go/NoGo task that can be assumed to induce different metacontrol states (persistence-biased vs. flexibility-biased). Aperiodic activity was estimated using the FOOOF toolbox in the EEG power spectrum. There was a higher aperiodic exponent and offset in NoGo trials compared with Go trials, in incongruent (Go) trials compared with congruent (Go) trials. Thus, aperiodic activity increases during persistence-heavy processing, but decreases during flexibility-heavy processing. These findings link aperiodic features of the EEG signal and concepts describing the dynamics of how cognitive control modes are applied. Therefore, the study substantially extends the importance of aperiodic activity in understanding cognitive functions.