Class â ¡ ferroptosis inducers are a novel therapeutic approach for t(4;14)-positive multiple myeloma.

Multiple myeloma (MM) is a clonal plasma cell malignancy characterized by genetic heterogeneity. The cytogenetic abnormality t(4;14) strongly predicts poor outcome in MM patients even in the era of novel drugs. Ferroptosis is a new approach to antitumor therapy, but the relationship between ferroptosis and MM cytogenetic abnormalities remains largely unclear. Here, we show that t(4;14)-positive but not t(4;14)-negative MM cells are susceptible to class II ferroptosis inducers (FINs) in a preclinical setting, which is dependent on the significant upregulation of the MM SET domain-containing protein (MMSET). Mechanistically, MMSET upregulates acyl-CoA synthetase long-chain family member 4 (ACSL4) transcription by binding to its promoter region, leading to increased polyunsaturated fatty acid (PUFA) levels and enhanced sensitivity of t(4;14)-positive MM to ferroptosis. Supplementation of PUFAs efficiently restores ferroptosis susceptibility of t(4;14)-negative MM. In addition, combination treatment of class II FINs and bortezomib in t(4;14)-positive MM attenuates cellular glutathione and induces both apoptosis and ferroptosis levels by inhibiting the increase of solute carrier family 7 member 11, demonstrating synergistic anti-tumor activity in vitro and in a xenograft model. Taken together, our findings suggest that targeting ferroptosis with class II FINs is a novel and promising therapeutic approach to improve the outcome of t(4;14)-positive MM.

Accelerated Charge Transfer through Interface Chemical Bonds in MoS2/TiO2 for Photocatalytic Conversion of Lignocellulosic Biomass to H2.

Solar photocatalytic H2 production from lignocellulosic biomass has attracted great interest, but it suffers from low photocatalytic efficiency owing to the absence of highly efficient photocatalysts. Herein, we designed and constructed ultrathin MoS2-modified porous TiO2 microspheres (MT) with abundant interface Ti-S bonds as photocatalysts for photocatalytic H2 generation from lignocellulosic biomass. Owing to the accelerated charge transfer related to Ti-S bonds, as well as the abundant active sites for both H2 and ●OH generation, respectively, related to the high exposed edge of MoS2 and the large specific surface area of TiO2, MT photocatalysts demonstrate good performance in the photocatalytic conversion of α-cellulose and lignocellulosic biomass to H2. The highest H2 generation rate of 849 µmol·g-1·h-1 and apparent quantum yield of 4.45% at 380 nm was achieved in α-cellulose aqueous solution for the optimized MT photocatalyst. More importantly, lignocellulosic biomass of corncob, rice hull, bamboo, polar wood chip, and wheat straw were successfully converted to H2 over MT photocatalysts with H2 generation rate of 10, 19, 36, 29, and 8 µmol·g-1·h-1, respectively. This work provides a guiding design approach to develop highly active photocatalysts via interface engineering for solar H2 production from lignocellulosic biomass.

Transcriptome analysis reveals hepatic disordered lipid metabolism, lipotoxic injury, and abnormal development in IUGR sheep fetuses due to maternal undernutrition during late pregnancy.

Although lipid metabolism in fetal livers under intrauterine growth restriction (IUGR) conditions has been widely studied, the implications of maternal undernutrition on fetal hepatic lipid metabolism, lipotoxic injury, and abnormal development remain largely unknown. Therefore, this study investigated the effects of maternal undernutrition on disordered hepatic lipid metabolism, lipotoxic injury, and abnormal development in IUGR sheep fetuses using transcriptome analysis. Seventeen singleton ewes were randomly divided into three groups on day 90 of pregnancy: a control group (CG; 0.63 MJ metabolic energy/body weight (ME/BW)0.75/day, n = 5), maternal undernutrition group 1 (MU1; 0.33 MJ ME/BW0.75/day, n = 6), and maternal undernutrition group 2 (MU2; 0.20 MJ ME/BW0.75/day, n = 6). The fetuses were euthanized and recovered on day 130 of pregnancy. The levels of free fatty acids (FFA) in maternal blood (P < 0.01), fetal blood (P < 0.01), and fetal livers (P < 0.05) were increased in the MU1 and MU2 groups, but fetal hepatic triglyceride (TG) levels in the MU2 group (P < 0.01) and ß-hydroxybutyrate levels in the MU1 and MU2 groups (P < 0.01) were decreased compared to the CG. Severe inflammatory cell infiltration and increased non-alcoholic fatty liver disease activity scores were observed in MU1 and MU2 fetuses (P < 0.01). Progressive deposition of fetal hepatic reticular fibers and collagen fibers in the fetal livers of the MU1 and MU2 groups and significant hepatic fibrosis were observed in the MU2 fetuses (P < 0.05). Gene set enrichment analysis showed that genes involved in lipid accumulation and FFA beta oxidation were downregulated in both MU groups compared to those in the controls. The fetal liver mRNA expression of the ß-oxidation regulator, acetyl-CoA acetyltransferase 1, and the TCA regulator, isocitrate dehydrogenase were reduced in MU1 (P < 0.05) and MU2 (P < 0.01) fetuses, and downregulated mRNA expression of long chain fatty acid CoA ligase 1 (P < 0.05) and glycerol-3-phosphate acyltransferase (P < 0.01) was observed in MU2 fetuses. Differentially expressed genes (DEGs) in MU1 versus CG (360 DEGs) and MU2 versus CG (746 DEGs) were identified using RNA sequencing. Bioinformatics analyses of the 231 intersecting DEGs between MU1 versus CG and MU2 versus CG indicated that neutrophil extracellular traps (NETs) were induced and played a central role in fetal hepatic injury in IUGR sheep. Increased maternal blood myeloperoxidase (MPO) levels (P < 0.01), NE (Elane)-positive areas in fetal liver sections (P < 0.05), and fetal liver MPO protein expression (P < 0.01) were found in the MU1 and MU2 groups; however, MPO levels were reduced in the fetal membrane (P < 0.01) and fetal blood (P < 0.05) in the MU1 group, and in the maternal-fetal placenta and fetal blood in the MU2 group (P < 0.01). Analysis of gene expression trends in the intersecting DEGs between MU1 versus CG (129 DEGs) and MU2 versus CG (515 DEGs) further revealed that 30 hub genes were essential regulators of the G2/M cell cycle, all of which were associated with hepatocellular carcinoma. G0/G1 phase cells of the fetal liver were reduced in the MU1 (P < 0.05) and MU2 (P < 0.01) groups, whereas G2/M phase cells were elevated in the MU1 and MU2 groups (P < 0.01). The representatives of upregulated hub genes and fetal liver protein expression of maternal embryonic leucine zipper kinase and protein regulator of cytokinesis 1 were progressively enhanced in the MU1 and MU2 groups (P < 0.01), and topoisomerase II alpha protein expression in the MU2 group (P < 0.05), as expected. These results indicate that FFA overload, severe lipotoxic injury, and NETs were induced, and disease-promoting regulators of the G2/M cell cycle were upregulated in the fetal liver of IUGR sheep. These findings provide new insights into the pathogenesis of impaired hepatic lipid metabolism and abnormal development and the molecular origin of post-natal liver disease in IUGR due to maternal undernutrition. This information can support the development of new therapeutic strategies.

Intrinsic capacity decline as a predictor of functional disability in the elderly: A systematic review and meta-analysis.

OBJECTIVES: To examine the predictive value of intrinsic capacity decline on functional disability among the elderly. DESIGN: Meta-analysis. METHODS: PubMed, EMBASE, Web of Science, The Cochrane Library, Wanfang Database, China Knowledge Resource Integrated Database (CNKI), Weipu Database (VIP), and Chinese Biomedical Database (CBM) were searched for relevant studies published from the inception until June 1, 2024. Stata 17.0 software was used to perform the meta-analysis. The methodological quality was evaluated using the Newcastle Ottawa Scale. The overall quality of evidence used GRADE guidelines to assess. A study protocol was registered in PROSPERO (CRD42023475461). RESULTS: The meta-analysis included 8 cohort studies including 9744 elderly people. Functional disability including ADL disability (n = 6) and IADL disability (n = 7). The results showed that intrinsic capacity decline could predict ADL disability (HR = 1.08, 95 %CI 1.04-1.12; I2 = 98.2 %, P < 0.001) and IADL disability (HR = 1.11, 95 %CI 1.05-1.17; I2 = 96.4 %, P < 0.001). The overall risk of bias was low. And the grade of evidence that assessed by GRADE guidelines was rated as moderate. CONCLUSIONS: Intrinsic capacity decline is a predictor of functional disability in the elderly. Therefore, screening intrinsic capacity decline has important clinical implications for early identifying the risk of functional disability, which contributes to providing individualized interventions ahead of potential functional disability for the elderly, thereby preventing functional disability, improving the quality of life and promoting healthy aging.

Dendrobine Ameliorates Glucocorticoid-Induced Osteoporosis by Promoting Osteogenesis through JNK/p38 MAPK Pathway Activation and GR Nuclear Translocation Inhibition.

Glucocorticoid-induced osteoporosis (GIOP) is the common reason for secondary osteoporosis. Dendrobine (DEN) is the major biologically active component of Dendrobium officinale with anti-inflammatory and antiaging properties. Whether DEN could alleviate osteogenic inhibition in GIOP rats is still unknown. The influence on osteogenic function caused by DEN on dexamethasone-treated bone marrow mesenchymal stem cells and rats was observed. The in vitro results showed that DEN reversed the inhibition of osteogenic differentiation by dexamethasone. Moreover, DEN supplementation attenuated dexamethasone-induced bone loss in vivo. DEN activated JNK and p38 MAPK pathways and restrained GR nuclear translocation, which could be prevented by the JNK (SP600125) or p38 (SB203580) pathway inhibitor. This study verified that DEN alleviated dexamethasone-induced nuclear translocation of GR, and inhibition of osteogenesis via JNK and p38 pathways, laying the foundation for DEN as a therapeutic agent for GIOP.

Treatment plan complexity quantification for predicting gamma passing rates in patient-specific quality assurance for stereotactic volumetric modulated arc therapy.

PURPOSE: To investigate the beam complexity of stereotactic Volumetric Modulated Arc Therapy (VMAT) plans quantitively and predict gamma passing rates (GPRs) using machine learning. METHODS: The entire dataset is exclusively made of stereotactic VMAT plans (301 plans with 594 beams) from Varian Edge LINAC. The GPRs were analyzed using Varian's portal dosimetry with 2%/2 mm criteria. A total of 27 metrics were calculated to investigate the correlation between metrics and GPRs. Random forest and gradient boosting models were developed and trained to predict the GPRs based on the extracted complexity features. The threshold values of complexity metric were obtained to predict a given beam to pass or fail from ROC curve analysis. RESULTS: The three moderately significant values of Spearman's rank correlation to GPRs were 0.508 (p < 0.001), 0.445 (p < 0.001), and -0.416 (p < 0.001) for proposed metric LAAM, the ratio of the average aperture area over jaw area (AAJA) and index of modulation, respectively. The random forest method achieved 98.74% prediction accuracy with mean absolute error of 1.23% using five-fold cross-validation, and 98.71% with 1.25% for gradient boosting regressor method, respectively. LAAM, leaf travelling distance (LT), AAJA, LT modulation complexity score (LTMCS) and index of modulation, were the top five most important complexity features. The LAAM metric showed the best performance with AUC value of 0.801, and threshold value of 0.365. CONCLUSIONS: The calculated metrics were effective in quantifying the complexity of stereotactic VMAT plans. We have demonstrated that the GPRs could be accurately predicted using machine learning methods based on extracted complexity metrics. The quantification of complexity and machine learning methods have the potential to improve stereotactic treatment planning and identify the failure of QA results promptly.

Advancements and prospects of novel biologicals for myasthenia gravis: toward personalized treatment based on autoantibody specificities.

Myasthenia gravis (MG) is an antibody-mediated autoimmune disease with a prevalence of 150-250 cases per million individuals. Autoantibodies include long-lived antibodies against the acetylcholine receptor (AChR), mainly of the IgG1 subclass, and IgG4, produced almost exclusively by short-lived plasmablasts, which are prevalent in muscle-specific tyrosine kinase (MuSK) myasthenia gravis. Numerous investigations have demonstrated that MG patients receiving conventional medication today still do not possess satisfactory symptom control, indicating a substantial disease burden. Subsequently, based on the type of the autoantibody and the pathogenesis, we synthesized the published material to date and reached a conclusion regarding the literature related to personalized targeted therapy for MG. Novel agents for AChR MG have shown their efficacy in clinical research, such as complement inhibitors, FcRn receptor antagonists, and B-cell activating factor (BAFF) inhibitors. Rituximab, a representative drug of anti-CD20 therapy, has demonstrated benefits in treatment of MuSK MG patients. Due to the existence of low-affinity antibodies or unidentified antibodies that are inaccessible by existing methods, the treatment for seronegative MG remains complicated; thus, special testing and therapy considerations are necessary. It may be advantageous to initiate the application of novel biologicals at an early stage of the disease. Currently, therapies can also be combined and individualized according to different types of antibodies. With such a wide range of drugs, how to tailor treatment strategies to patients with various conditions and find the most suitable solution for each MG profile are our necessary and urgent aims.

PRT-Net: a progressive refinement transformer for dose prediction to guide ovarian transposition.

Introduction: Young cervical cancer patients who require ovarian transposition usually have their ovaries moved away from the pelvic radiotherapy (RT) field before radiotherapy. The dose of ovaries during radiotherapy is closely related to the location of the ovaries. To protect ovarian function and avoid ovarian dose exceeding the limits, a safe location of transposed ovary must be determined prior to surgery. Methods: For this purpose, we input the patient's preoperative CT into a neural network model to predict the dose distribution. Surgeons were able to quickly locate low-dose regions based on the dose distribution before surgery, thus determining the safe location of the transposed ovary. In this work, we proposed a new progressive refinement transformer model PRT-Net that can generate dose prediction at multiple scale resolutions in one forward propagation, and refine the dose prediction using prediction details from low to high resolution based on a deep supervision strategy. A multi-loss function fusion algorithm was also built to fit the prediction results under different loss dimensions. The clinical feasibility of the method was verified through an actual cases. Results and discussion: Therefore, using PRT-Net to predict the dose distribution by preoperative CT in cervical cancer patients can assist clinicians to perform ovarian transposition surgery and prevent patients' ovaries from exceeding the prescribed dose limit in postoperative radiotherapy.

Cocrystal Prediction of Nifedipine Based on the Graph Neural Network and Molecular Electrostatic Potential Surface.

Nifedipine (NIF) is a dihydropyridine calcium channel blocker primarily used to treat conditions such as hypertension and angina. However, its low solubility and low bioavailability limit its effectiveness in clinical practice. Here, we developed a cocrystal prediction model based on Graph Neural Networks (CocrystalGNN) for the screening of cocrystals with NIF. And scoring 50 coformers using CocrystalGNN. To validate the reliability of the model, we used another prediction method, Molecular Electrostatic Potential Surface (MEPS), to verify the prediction results. Subsequently, we performed a second validation using experiments. The results indicate that our model achieved high performance. Ultimately, cocrystals of NIF were successfully obtained and all cocrystals exhibited better solubility and dissolution characteristics compared to the parent drug. This study lays a solid foundation for combining virtual prediction with experimental screening to discover novel water-insoluble drug cocrystals.

Innate protection against intrarectal SIV acquisition by a live SHIV vaccine.

Identifying immune correlates of protection is a major challenge in AIDS vaccine development. Anti-Envelope antibodies have been considered critical for protection against SIV/HIV (SHIV) acquisition. Here, we evaluated the efficacy of an SHIV vaccine against SIVmac251 challenge, where the role of antibody was excluded, as there was no cross-reactivity between SIV and SHIV envelope antibodies. After 8 low-dose intrarectal challenges with SIVmac251, 12 SHIV-vaccinated animals demonstrated efficacy, compared with 6 naive controls, suggesting protection was achieved in the absence of anti-envelope antibodies. Interestingly, CD8+ T cells (and some NK cells) were not essential for preventing viral acquisition, as none of the CD8-depleted macaques were infected by SIVmac251 challenges. Initial investigation of protective innate immunity revealed that protected animals had elevated pathways related to platelet aggregation/activation and reduced pathways related to interferon and responses to virus. Moreover, higher expression of platelet factor 4 on circulating platelet-leukocyte aggregates was associated with reduced viral acquisition. Our data highlighted the importance of innate immunity, identified mechanisms, and may provide opportunities for novel HIV vaccines or therapeutic strategy development.

Determinants of macaques' space use: A test for the ecological constraints model using GPS collars.

As a central topic in Behavioral Ecology, animal space use involves dynamic responses to social and ecological factors. We collared 22 rhesus macaques (Macaca mulatta) from six groups on Neilingding Island, China, and collected 80,625 hourly fixes over a year. Using this high-resolution location data set, we quantified the macaques' space use at the individual level and tested the ecological constraints model while considering various environmental and human interfering factors. As predicted by the ecological constraints model, macaques in larger groups had longer daily path lengths (DPLs) and larger home ranges. We found an inverted U-shape relationship between mean daily temperatures and DPLs, indicating that macaques traveled farther on mild temperature days, while they decreased DPLs when temperatures were too high or too low. Anthropogenic food subsidies were positively correlated to DPLs, while the effect of rainfall was negative. Macaques decreased their DPLs and core areas when more flowers and less leaves were available, suggesting that macaques shifted their space use patterns to adapt to the seasonal differences in food resources. By applying GPS collars on a large number of individuals living on a small island, we gained valuable insights into within-group exploitation competition in wild rhesus macaques.

Protocol for extracting and isolating porcine bone-marrow-derived macrophages from ribs.

Due to anatomical and biological similarities with humans, pigs are increasingly used for inflammation- and immune-related studies in biomedical research, including the field of osteonecrosis and osteoimmunology. Here, we present a protocol for rib extraction, isolation of the bone marrow by centrifugation, and processing to obtain bone-marrow-derived macrophages (BMDMs). Then, we describe the procedures of in vitro experiments to evaluate the cell phenotype. For complete details on the use and execution of this protocol, please refer to Andre et al.1.

The "toxic window" of amoxicillin exposure during pregnancy on long bone development in fetal mice.

AIMS: Amoxicillin is a broad-spectrum beta-lactam antibiotic used to treat infectious diseases in pregnant women. Studies have shown that prenatal amoxicillin exposure (PAmE) has developmental toxicity on fetal development. However, the effect of PAmE on long bone development has not been reported. This study aimed to investigate the "toxic window" of PAmE on long bone development and explore its possible mechanism in fetal mice. MATERIALS AND METHODS: Pregnant mice were administered amoxicillin by gavage at different stages (gestational day (GD)10-12 and GD16-18), different doses (150 and 300 mg/kg·d) and different courses (single and multiple courses). Fetal femurs were collected at GD18 and bone development related indicators were detected. KEY FINDINGS: The results showed that PAmE significantly reduced the length of the femur and primary ossification center of fetal mice, and inhibited the development of fetal growth plate. Meanwhile, PAmE inhibited the development of bone marrow mesenchymal stem cells, osteoclasts and endothelial cells in fetal long bone. Further, we found the fetal long bone developmental toxicity induced by PAmE was most significant at late-pregnancy (GD16-18), high dose (300 mg/kg·d) and multiple-course group. Besides, PAmE inhibited the expression of Wnt/ß-catenin signaling pathway in fetal long bone. The ß-catenin mRNA expression was significantly positively correlated with the development indexes of fetal long bone. SIGNIFICANCE: PAmE has toxic effects on long bone development, and there was an obvious "toxic window" of PAmE on the long bone development in fetal mice. The Wnt/ß-catenin signaling pathway may mediate PAmE-induced fetal long bone development inhibition.

Multifunctional Nanofibrous Hollow Microspheres for Enhanced Periodontal Bone Regeneration.

Destructive periodontitis destroys alveolar bone and eventually leads to tooth loss. While guided bone regeneration, which is based on creating a physical barrier to hinder the infiltration of epithelial and connective tissues into defect sites, has been widely used for alveolar bone regeneration, its outcomes remain variable. In this work, a multifunctional nanofibrous hollow microsphere (NFHMS) is developed for enhanced alveolar bone regeneration. The NFHMS is first prepared via combining a double emulsification and a thermally induced phase separation process. Next, E7, a short peptide with high specific affinity to bone marrow-derived stem cells (BMSCs), is conjugated onto the surface of NFHMS. After that, bone forming peptide (BFP), a short peptide derived from bone morphology protein 7 is loaded in calcium phosphate (CaP) nanoparticles, which are further encapsulated in the hollow space of the NFHMS-E7 to form NFHMS-E7-CaP/BFP. The NFHMS-E7-CaP/BFP selectively promoted the adhesion of BMSCs and expelled the adhesion of fibroblasts and epithelial cells. In addition, the BFP is sustainedly released from the NFHMS-E7-CaP/BFP to enhance the osteogenesis of BMSCs. A rat challenging fenestration defect model showed that the NFHMS-E7-CaP/BFP significantly enhanced alveolar bone tissue regeneration. This work provides a novel bioengineering approach for guided bone regeneration.

A study of the effects of screen exposure on the neuropsychological development in children with autism spectrum disorders based on ScreenQ.

PURPOSE: To investigate the relationship between multi-dimensional aspects of screen exposure and autistic symptoms, as well as neuropsychological development in children with ASD. METHODS: We compared the ScreenQ and Griffiths Development Scales-Chinese Language Edition (GDS-C) of 636 ASD children (40.79 ± 11.45 months) and 43 typically developing (TD) children (42.44 ± 9.61 months). Then, we analyzed the correlations between ScreenQ and Childhood Autism Rating Scale (CARS), and GDS-C. We further used linear regression model to analyze the risk factors associated with high CARS total scores and low development quotients (DQs) in children with ASD. RESULTS: The CARS of children with ASD was positively correlated with the ScreenQ total scores and "access, frequency, co-viewing" items of ScreenQ. The personal social skills DQ was negatively correlated with the "access, frequency, content, co-viewing and total scores" of ScreenQ. The hearing-speech DQ was negatively correlated with the "frequency, content, co-viewing and total scores" of ScreenQ. The eye-hand coordination DQ was negatively correlated with the "frequency and total scores" of ScreenQ. The performance DQ was negatively correlated with the "frequency" item of ScreenQ. CONCLUSION: ScreenQ can be used in the study of screen exposure in children with ASD. The higher the ScreenQ scores, the more severe the autistic symptoms tend to be, and the more delayed the development of children with ASD in the domains of personal-social, hearing-speech and eye-hand coordination. In addition, "frequency" has the greatest impact on the domains of personal social skills, hearing-speech, eye-hand coordination and performance of children with ASD.

Feature Matching of Microsecond-Pulsed Magnetic Fields Combined with Fe3O4 Particles for Killing A375 Melanoma Cells.

The combination of magnetic fields and magnetic nanoparticles (MNPs) to kill cancer cells by magneto-mechanical force represents a novel therapy, offering advantages such as non-invasiveness, among others. Pulsed magnetic fields (PMFs) hold promise for application in this therapy due to advantages such as easily adjustable parameters; however, they suffer from the drawback of narrow pulse width. In order to fully exploit the potential of PMFs and MNPs in this therapy, while maximizing therapeutic efficacy within the constraints of the narrow pulse width, a feature-matching theory is proposed, encompassing the matching of three aspects: (1) MNP volume and critical volume of Brownian relaxation, (2) relaxation time and pulse width, and (3) MNP shape and the intermittence of PMF. In the theory, a microsecond-PMF generator was developed, and four kinds of MNPs were selected for in vitro cell experiments. The results demonstrate that the killing rate of the experimental group meeting the requirements of the theory is at least 18% higher than the control group. This validates the accuracy of our theory and provides valuable guidance for the further application of PMFs in this therapy.

Selenoprotein I is indispensable for ether lipid homeostasis and proper myelination.

Selenoprotein I (SELENOI) catalyzes the final reaction of the CDP-ethanolamine branch of the Kennedy pathway, generating the phospholipids phosphatidylethanolamine (PE) and plasmenyl-PE. Plasmenyl-PE is a key component of myelin and is characterized by a vinyl ether bond that preferentially reacts with oxidants, thus serves as a sacrificial antioxidant. In humans, multiple loss-of-function mutations in genes affecting plasmenyl-PE metabolism have been implicated in hereditary spastic paraplegia, including SELENOI. Herein, we developed a mouse model of nervous system-restricted SELENOI deficiency that circumvents embryonic lethality caused by constitutive deletion and recapitulates phenotypic features of hereditary spastic paraplegia. Resulting mice exhibited pronounced alterations in brain lipid composition, which coincided with motor deficits and neuropathology including hypomyelination, elevated reactive gliosis, and microcephaly. Further studies revealed increased lipid peroxidation in oligodendrocyte lineage cells and disrupted oligodendrocyte maturation both in vivo and in vitro. Altogether, these findings detail a critical role for SELENOI-derived plasmenyl-PE in myelination that is of paramount importance for neurodevelopment.

Preliminary Exploration of the Biophysical Mechanisms of Pulsed Magnetic Field- Induced Cell Permeabilization.

Pulsed magnetic field treatment can enhance cell membrane permeability, allowing large molecular substances that normally cannot pass through the cell membrane to enter the cell. This research holds significant prospects for biomedical applications. However, the mechanism underlying pulsed magnetic field-induced cell permeabilization remains unclear, impeding further progress in research related to pulsed magnetic field. Currently, hypotheses about the mechanism are struggling to explain experimental results. Therefore, this study developed a parameter-adjustable pulsed magnetic field generator and designed experiments. Starting from the widely accepted hypothesis of "induced electric fields by pulsed magnetic field," we conducted a preliminary exploration of the biophysical mechanisms underlying pulsed magnetic field-induced cell permeabilization. Finally, we have arrived at an intriguing conclusion: under the current technical parameters, the impact of the pulsed magnetic field itself is the primary factor influencing changes in cell membrane permeability, rather than the induced electric field. This conclusion holds significant implications for understanding the biophysical mechanisms behind pulsed magnetic field therapy and its potential biomedical applications.

Hibiscus manihot L. flower extract induces anticancer activity through modulation of apoptosis and autophagy in A549 cells.

Lung cancer is a major public health issue and heavy burden in China and worldwide due to its high incidence and mortality without effective treatment. It's imperative to develop new treatments to overcome drug resistance. Natural products from food source, given their wide-ranging and long-term benefits, have been increasingly used in tumor prevention and treatment. This study revealed that Hibiscus manihot L. flower extract (HML) suppressed the proliferation and migration of A549 cells in a dose and time dependent manner and disrupting cell cycle progression. HML markedly enhanced the accumulation of ROS, stimulated the dissipation of mitochondrial membrane potential (MMP) and that facilitated mitophagy through the loss of mitochondrial function. In addition, HML induced apoptosis by activation of the PTEN-P53 pathway and inhibition of ATG5/7-dependent autophagy induced by PINK1-mediated mitophagy in A549 cells. Moreover, HML exert anticancer effects together with 5-FU through synergistic effect. Taken together, HML may serve as a potential tumor prevention and adjuvant treatment for its functional attributes.

Sesquiterpenoids and hexanorcucurbitacin from Aquilaria malaccensis agarwood with anti-inflammatory effects by inhibiting the STAT1/AKT/MAPK/NLRP3 pathway.

Seven unknown compounds 1-7, including four sesquiterpenoids, one azulene-type, one indene-type, and one rare hexanorcucurbitacin, together with eleven knowns ones (8-16), were isolated from the agarwood chips of Aquilaria malaccensis. The structures of the isolated compounds were elucidated by extensive spectroscopic methods such as mass spectrometry, UV, IR, NMR spectroscopy. The precise stereo-chemical configurations of new compounds were determined by calculated ECD spectra data, as well as a single-crystal X-ray diffraction analysis. The isolated compounds 1-7 were evaluated by estimating the levels of nitric oxide (NO), TNF-α, and the expression of enzyme iNOS, and COX-2. Among them, a rare hexanortriterpenoid (7) derived from a cucurbitane-type triterpenoid showed the significantly attenuated neuro-inflammatory effects via the STAT1/AKT/MAPK/NLRP3 signaling pathway on the mechanistic studies.