Vertebral marrow fat fraction is associated with circulating RANKL in postmenopausal females.

Objective: To investigate the relationship between circulating receptor activator of nuclear factor-kappa B ligand (RANKL) levels and marrow adipose tissue in postmenopausal females. Methods: A total of 164 postmenopausal females were included in the study. Serum levels of osteoprotegerin (OPG) and RANKL were measured using ELISA kits. Body composition and bone mineral density (BMD) were assessed using dual-energy X-ray absorptiometry. Complex-based chemical shift imaging-based MRI was employed to evaluate the vertebral marrow proton density fat fraction (PDFF). A multivariate linear regression model was utilized to analyze the predictive effects of PDFF and BMD on circulating levels of OPG and RANKL. Results: Simple regression analysis showed significant associations among the marrow PDFF, BMD at either site, serum RANKL, and the RANKL/OPG ratio. In multivariate linear regression models, marrow PDFF was found to have a positive correlation (ß = 3.15, 95% CI 2.60 to 3.70) and BMD had negative correlations (ß = -0.200, 95% CI -0.348 to -0.051 for vertebral BMD; ß = -0.383, 95% CI -0.589 to -0.177 for total hip BMD; and ß =-0.393, 95% CI -0.598 to -0.188 for femoral neck BMD, all p < 0.01) with circulating soluble RANKL levels after adjusting for age, body mass index, physical activity, total fat mass, android/gynoid ratio, and lean mass. Similar results were observed for the RANKL/OPG ratio. Additionally, multivariate linear regression analyses revealed that marrow PDFF was a significant independent contributor of circulating soluble RANKL (ß = 1.34, 95% CI 1.10 to 1.58, p < 0.001) after further controlling for BMD. However, marrow PDFF or BMD had no associations with circulating levels of OPG after adjusting for all potential confounders mentioned above. Conclusions: Vertebral marrow fat fraction is independently associated with circulating soluble RANKL levels in postmenopausal females.

Novel Helicoma and Neohelicosporium (Tubeufiaceae, Tubeufiales) species and two new host records of Helicoma on tropical palms (Arecaceae) from China.

Asexual species of Tubeufiaceae are characterised as helicosporous hyphomycetes and are abundantly discovered in tropical and subtropical regions. The present study collected helicosporous fungal samples from rotting tissues of Caryotamitis, Elaeisguineensis and E.oleifera in Xishuangbanna, Yunan Province, China. Fungal isolates were identified, based on the morphological characteristics and multi-gene phylogeny with DNA sequence data of the internal transcribed spacer (ITS), part of the large subunit nuclear rRNA gene (LSU), translation elongation factor 1-alpha gene (tef 1-α) and RNA polymerase II second largest subunit gene (rpb2). Herein, we introduce three new species viz. Helicomaoleifera, Neohelicosporiumguineensis and N.xishuangbannaensis. In addition, we introduce two new host records of Helicomaguttulatum and H.rufum on Caryotamitis. The illustrations of all identified species, detailed descriptions and in-depth phylogenetic analyses are provided. Our results add new knowledge of fungal species associated with palm hosts in southern China. Moreover, our data will contribute to the biodiversity of fungi in tropical China.

[Transepithelial transport in vivo and in vitro and anti-inflammatory activity of cannabidiol].

This study used Caco-2 cells and normal rats to investigate the in vitro absorption characteristics and in vivo pharmacokinetic characteristics of cannabidiol(CBD) and explore the anti-inflammatory mechanism of CBD. The safe concentration range of CBD was determined by the CCK-8 assay, and then the effects of time, concentration, temperature, endocytosis inhibitors, and transport inhibitors on the transepithelial absorption and transport of CBD were assessed. The blood drug concentration was measured at different time points after oral administration in rats for pharmacokinetic profiling, and the pharmacokinetic parameters were calculated. The Caco-2 cell model of inflammation injury was established with lipopolysaccharide(LPS). The effects of CBD on lactate dehydrogenase(LDH) activity, transendothelial electrical resistance(TEER), and levels of inflammatory cytokines of the modeled cells were exami-ned, on the basis of which the anti-inflammatory mechanism of CBD was deciphered. The results showed that within the concentration range tested in this study, the CBD uptake by Caco-2 cells reached saturation at the time point of 2 h. Moreover, the CBD uptake was positively correlated with concentration and temperature and CBD could be endocytosed into the cells. CBD could penetrate Caco-2 cells through active transport pathways involving multidrug resistance-associate protein 2(MRP2) and breast cancer resistance protein(BCRP), while the addition of P-gp inhibitors had no effect on CBD transport. Rats exhibited rapid absorption of CBD, with the peak time(t_(max)) of(1.00±0.11) h, and fast elimination of CBD, with a half-life(t_(1/2)) of only(1.86±0.16) h. In addition, CBD significantly ameliorated the increased LDH activity and decreased TEER that were caused by inflammatory response. It maintained the intestinal barrier by down-regulating the expression of pro-inflammatory cytokines interleukin-8(IL-8), interleukin-1 beta(IL-1ß) and tumor necrosis factor-α(TNF-α), thus exerting anti-inflammatory effects.

Research progress of gene therapy combined with tissue engineering to promote bone regeneration.

Gene therapy has emerged as a highly promising strategy for the clinical treatment of large segmental bone defects and non-union fractures, which is a common clinical need. Meanwhile, many preclinical data have demonstrated that gene and cell therapies combined with optimal scaffold biomaterials could be used to solve these tough issues. Bone tissue engineering, an interdisciplinary field combining cells, biomaterials, and molecules with stimulatory capability, provides promising alternatives to enhance bone regeneration. To deliver and localize growth factors and associated intracellular signaling components into the defect site, gene therapy strategies combined with bioengineering could achieve a uniform distribution and sustained release to ensure mesenchymal stem cell osteogenesis. In this review, we will describe the process and cell molecular changes during normal fracture healing, followed by the advantages and disadvantages of various gene therapy vectors combined with bone tissue engineering. The growth factors and other bioactive peptides in bone regeneration will be particularly discussed. Finally, gene-activated biomaterials for bone regeneration will be illustrated through a description of characteristics and synthetic methods.

Delayed sustained lung inflation for preterm neonates in neonatal intensive care unit: a randomized controlled trial.

INTRODUCTION: Sustained lung inflation (SLI) right after birth to decrease the use of mechanical ventilation of preterm infants is controversial because of potential harm. This randomized controlled trial was conducted to evaluate the effectiveness and safety of delayed SLI in neonatal intensive care unit (NICU). METHODS: Preterm neonates requiring continuous positive airway pressure after birth were eligible for enrollment. In the experimental group, SLI with 20 cm H2O for 15 s was conducted by experienced staff in the NICU between 30 min and 24 h after birth. RESULTS: A total of 45 neonates were enrolled into this study, including 24 in the experimental group and 21 in the control group. There was no significant difference in the birth condition between the experimental and control groups, including gestational age (p = 0.151), birth weight (p = 0.692), and Apgar score at 1 min (p = 0.410) and 5 min (p = 0.518). The results showed the duration of respiratory support was shorter in the experimental group than the control group (p = 0.044). In addition, there was no significant difference in the other outcomes, such as pneumothorax, patent ductus arteriosus, and bronchopulmonary dysplasia. CONCLUSION: Our findings indicate that sustained inflation conducted by experienced staff in the NICU is safe. The data suggest that SLI conducted by experienced staff in the NICU after stabilization could serve as an alternative management for preterm infants with respiratory distress. However, the reduction in use of respiratory support should be interpreted cautiously as a result of limited sample size. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN) Clinical Trials Registry: UMIN000052797 (retrospectively registered).

Sonic hedgehog signaling facilitates pyroptosis in mouse heart following ischemia/reperfusion via enhancing the formation of CARD10-BCL10-MALT1 complex.

Pyroptosis has been found to contribute to myocardial ischemia/reperfusion (I/R) injury, but the exact mechanisms that initiate myocardial pyroptosis are not fully elucidated. Sonic hedgehog (SHH) signaling is activated in heart suffered I/R, and intervention of SHH signaling has been demonstrated to protect heart from I/R injury. Caspase recruitment domain-containing protein 10 (CARD10)-B cell lymphoma 10 (BCL10)-mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) (CBM) complex could transduce signals from the membrane and induce inflammatory pathways in non-hematopoietic cells, which could be a downstream effector of SHH signaling pathway. This study aims to explore the role of SHH signaling in I/R-induced myocardial pyroptosis and its relationship with the CBM complex. C57BL/6J mice were subjected to 45 min-ischemia followed by 24 h-reperfusion to establish a myocardial I/R model, and H9c2 cells underwent hypoxia/reoxygenation (H/R) to mimic myocardial I/R model in vitro. Firstly, SHH signaling was significantly activated in heart suffered I/R in an autocrine- or paracrine-dependent manner via its receptor PTCH1, and inhibition of SHH signaling decreased myocardial injury via reducing caspase-11-dependent pyroptosis, concomitant with attenuating CBM complex formation. Secondly, suppression of SHH signaling decreased protein kinase C α (PKCα) level, but inhibition of PKCα attenuated CBM complex formation without impacting the protein levels of SHH and PTCH1. Finally, disruption of the CBM complex prevented MALT1 from recruiting of TRAF6, which was believed to trigger the caspase-11-dependent pyroptosis. Based on these results, we conclude that inhibition of SHH signaling suppresses pyroptosis via attenuating PKCα-mediated CARD10-BCL10-MALT1 complex formation in mouse heart suffered I/R.

Comprehensive evaluation of Chinese herbal compound prescriptions for postoperative spinal cord injury: A network meta-analysis of randomized controlled trials.

Background: Spinal cord injury (SCI) is a catastrophic condition associated with spinal nerve damage, which can lead to complete or partial loss of sensory and motor functions. Chinese herbal compound prescriptions (CHCP) have shown varying degrees of therapeutic effects on spinal cord injuries. However, there is a significant lack of clinical evidence-based research to substantiate these effects. Purpose: This study aims to thoroughly assess the viability of CHCPs in postoperative SCI through network meta-analysis. Methods: Computer searches were conducted across multiple databases, including PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang, VIP, and CBM, from their inception until May 2024. The meta-analysis adhered to the PRISMA guidelines and was registered in the PROSPERO database (CRD42023462686). A network meta-analysis was performed using the BUGSnet software package via R. Study design: A network meta-analysis of randomized clinical trials (RCTs). Results: A total of 26 RCTs involving 1848 patients were ultimately included. The network meta-analysis revealed the effectiveness in improving ASIA motor score as follows: "HQGZD" > "Other Decoctions" > "BYHWD" > "TDHXD" > "THCQD" > "Surgery". For ASIA sensory score, the effectiveness ranking was: "HQGZD" > "Other Decoctions" > "BYHWD" > "TDHXD" > "THCQD" > "Surgery". Additionally, the experimental group had a higher ADL score compared to the control group, with a statistically difference [SMD = 1.08, 95 % CI = (0.88, 1.27), p < 0.05]. The experimental group had fewer adverse events compared to the control group, with a statistically difference [RR = 0.41, 95 % CI (0.22, 0.78), p < 0.05]. Conclusion: The findings suggest that CHCP can mprove postoperative ASIA motor and sensory scores, enhance ADL scores, and reduce adverse events following SCI surgery. Specifically, combining surgery with Huangqi Guizhi Wuwu Decoction or Buyang Huanwu Decoction may provide superior therapeutic effects in SCI treatment. Integrating CHCP into postoperative care for SCI patients may offer potential benefits.

Feasibility and effectiveness of cardiac telerehabilitation for older adults with coronary heart disease: A pilot randomized controlled trial.

Background: Cardiac rehabilitation is a beneficial multidisciplinary treatment of exercise promotion, patient education, risk factor management, and psychosocial counseling for people with coronary heart disease (CHD) that is underutilized due to substantial disparities in access, referral, and participation. Empirical studies suggest that cardiac telerehabilitation (CTR) have safety and efficacy comparable to traditional in-person cardiac rehabilitation, however, older adults are under-reported with effectiveness, feasibility, and usability remains unclear. Methods: The study randomized 43 older adults (84 % males) to the 12-week CTR intervention or standard of care. Guided by Social Cognitive Theory, participants received individualized in-person assessment and e-coaching sessions, followed by CTR usage at home. Data were collected at baseline (T0), six-week (T1), and 12-week (T2). Results: Participants in the CTR intervention group showed significant improvement in daily steps (T1: ß = 4126.58, p = 0.001; T2: ß = 5285, p = 0.01) and health-promoting lifestyle profile (T1: ß = 23.26, p < 0.001; T2: ß = 12.18, p = 0.008) across study endpoints. Twenty participants completed the intervention, with 40 % used the website for data-uploading or experiential learning, 90 % used the pedometer for tele-monitoring. Improving awareness of rehabilitation and an action focus were considered key facilitators while physical discomforts and difficulties in using the technology were described as the main barriers. Conclusions: The CTR is feasible, safe and effective in improving physical activity and healthy behaviors in older adults with CHD. Considering the variation in individual cardiovascular risk factors, full-scale RCT with a larger sample is needed to determine the effect of CTR on psychological symptoms, body weight and blood pressure, and quality of life.

Dominant Charge Density Order in TaTe_{4}.

Electronic orders such as charge density wave (CDW) and superconductivity raise exotic physics and phenomena as evidenced in recently discovered kagome superconductors and transition metal chalcogenides. In most materials, CDW induces a weak, perturbative effect, manifested as shadow bands, minigaps, resistivity kinks, etc. Here we demonstrate a unique example-transition metal tetratellurides TaTe_{4}, in which the CDW order dominates the electronic structure and transport properties. Using angle-resolved photoemission spectroscopy, we found that the band structure of CDW TaTe_{4} is characterized by small, bulk electron pockets. Density functional theory analyses reveal their CDW origin from the folding of the original, large Fermi pockets. Importantly, the CDW induced pockets result in prominent frequencies in the quantum oscillation of the magnetoresistance. Satisfactory agreements are reached between results from photoemission spectroscopy, density functional theory, and quantum oscillation, concerning the shape, size, location, and angle dependence of the CDW pockets. Our results underline transition metal tetratellurides as an outstanding example for exploring the interplay between CDW, pressure induced superconductivity, and potential topological states under strong field.

A Competition for the Diagnosis of Myopic Maculopathy by Artificial Intelligence Algorithms.

Importance: Myopic maculopathy (MM) is a major cause of vision impairment globally. Artificial intelligence (AI) and deep learning (DL) algorithms for detecting MM from fundus images could potentially improve diagnosis and assist screening in a variety of health care settings. Objectives: To evaluate DL algorithms for MM classification and segmentation and compare their performance with that of ophthalmologists. Design, Setting, and Participants: The Myopic Maculopathy Analysis Challenge (MMAC) was an international competition to develop automated solutions for 3 tasks: (1) MM classification, (2) segmentation of MM plus lesions, and (3) spherical equivalent (SE) prediction. Participants were provided 3 subdatasets containing 2306, 294, and 2003 fundus images, respectively, with which to build algorithms. A group of 5 ophthalmologists evaluated the same test sets for tasks 1 and 2 to ascertain performance. Results from model ensembles, which combined outcomes from multiple algorithms submitted by MMAC participants, were compared with each individual submitted algorithm. This study was conducted from March 1, 2023, to March 30, 2024, and data were analyzed from January 15, 2024, to March 30, 2024. Exposure: DL algorithms submitted as part of the MMAC competition or ophthalmologist interpretation. Main Outcomes and Measures: MM classification was evaluated by quadratic-weighted κ (QWK), F1 score, sensitivity, and specificity. MM plus lesions segmentation was evaluated by dice similarity coefficient (DSC), and SE prediction was evaluated by R2 and mean absolute error (MAE). Results: The 3 tasks were completed by 7, 4, and 4 teams, respectively. MM classification algorithms achieved a QWK range of 0.866 to 0.901, an F1 score range of 0.675 to 0.781, a sensitivity range of 0.667 to 0.778, and a specificity range of 0.931 to 0.945. MM plus lesions segmentation algorithms achieved a DSC range of 0.664 to 0.687 for lacquer cracks (LC), 0.579 to 0.673 for choroidal neovascularization, and 0.768 to 0.841 for Fuchs spot (FS). SE prediction algorithms achieved an R2 range of 0.791 to 0.874 and an MAE range of 0.708 to 0.943. Model ensemble results achieved the best performance compared to each submitted algorithms, and the model ensemble outperformed ophthalmologists at MM classification in sensitivity (0.801; 95% CI, 0.764-0.840 vs 0.727; 95% CI, 0.684-0.768; P = .006) and specificity (0.946; 95% CI, 0.939-0.954 vs 0.933; 95% CI, 0.925-0.941; P = .009), LC segmentation (DSC, 0.698; 95% CI, 0.649-0.745 vs DSC, 0.570; 95% CI, 0.515-0.625; P < .001), and FS segmentation (DSC, 0.863; 95% CI, 0.831-0.888 vs DSC, 0.790; 95% CI, 0.742-0.830; P < .001). Conclusions and Relevance: In this diagnostic study, 15 AI models for MM classification and segmentation on a public dataset made available for the MMAC competition were validated and evaluated, with some models achieving better diagnostic performance than ophthalmologists.

Neural Memory State Space Models for Medical Image Segmentation.

With the rapid advancement of deep learning, computer-aided diagnosis and treatment have become crucial in medicine. UNet is a widely used architecture for medical image segmentation, and various methods for improving UNet have been extensively explored. One popular approach is incorporating transformers, though their quadratic computational complexity poses challenges. Recently, State-Space Models (SSMs), exemplified by Mamba, have gained significant attention as a promising alternative due to their linear computational complexity. Another approach, neural memory Ordinary Differential Equations (nmODEs), exhibits similar principles and achieves good results. In this paper, we explore the respective strengths and weaknesses of nmODEs and SSMs and propose a novel architecture, the nmSSM decoder, which combines the advantages of both approaches. This architecture possesses powerful nonlinear representation capabilities while retaining the ability to preserve input and process global information. We construct nmSSM-UNet using the nmSSM decoder and conduct comprehensive experiments on the PH2, ISIC2018, and BU-COCO datasets to validate its effectiveness in medical image segmentation. The results demonstrate the promising application value of nmSSM-UNet. Additionally, we conducted ablation experiments to verify the effectiveness of our proposed improvements on SSMs and nmODEs.

Endoplasmic reticulum-targeted biomimetic nanoparticles induce apoptosis and ferroptosis by regulating endoplasmic reticulum function in colon cancer.

Colorectal cancer (CRC) is a major threat to human health, as it is one of the most common malignancies with a high incidence and mortality rate. The cancer cell membrane (CCM) has significant potential in targeted tumor drug delivery due to its membrane antigen-mediated homologous targeting ability. The endoplasmic reticulum (ER) in cancer cells plays a crucial role in apoptosis and ferroptosis. In this study, we developed an ER-targeted peptide-modified CCM-biomimetic nanoparticle-delivered lovastatin (LOV) nanomedicine delivery system (EMPP-LOV) for cancer treatment. Both in vitro and in vivo experiments demonstrated that EMPP could effectively target cancer cells and localize within the ER. EMPP-LOV modulated ER function to promote apoptosis and ferroptosis in tumor cells. Furthermore, synergistic antitumor efficacy was observed in both in vitro and in vivo models. EMPP-LOV induced apoptosis in CRC cells by over-activating endoplasmic reticulum stress and promoted ferroptosis by inhibiting the mevalonate pathway, leading to synergistic tumor growth inhibition with minimal toxicity to major organs. Overall, the EMPP-LOV delivery system, with its subcellular targeting capability within tumor cells, presents a promising therapeutic platform for CRC treatment.

Sodium butyrate improves cognitive dysfunction in high-fat diet/ streptozotocin-induced type 2 diabetic mice by ameliorating hippocampal mitochondrial damage through regulating AMPK/PGC-1α pathway.

Cognitive dysfunction is an important comorbidity of type 2 diabetes mellitus (T2DM). Sodium butyrate (NaB) is a short-chain fatty acid and has an effect improving T2DM-associated cognitive dysfunction. Using a high-fat diet (HFD)/streptozotocin (STZ)-induced T2DM mouse model, the present study investigated the mechanism involved in the beneficial effect of butyrate on diabetic cognitive dysfunction, with a focus on ameliorating mitochondrial damage through regulating the adenosine monophosphate-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1α (AMPK/PGC-1α) pathway considering the important role of mitochondrial impairments in the occurrence of T2DM-associated cognitive dysfunction. We found, based on reconfirmation of the improvement of NaB on cognitive impairment, that NaB treatment improved damaged synaptic structural plasticity including the decrease in dendritic spine density and downregulation in the expression of postsynaptic density protein 95 and synaptophysin in the hippocampus in the model mice. NaB treatment also ameliorated mitochondrial ultrastructural damage, increased mitochondrial membrane potential and adenosine 5'-triphosphate content, and improved mitochondrial biogenesis and dynamics in the model mice. Furthermore, the expression of phosphorylated AMPK and PGC-1α was upregulated after NaB treatment in the model mice. In particular, the above beneficial effects of NaB were blocked by the inhibition of either AMPK or PGC-1α. In conclusion, NaB treatment improved cognitive impairment and damaged synaptic structural plasticity in the hippocampus by ameliorating damage to mitochondrial morphology and function through regulating the AMPK/PGC-1α pathway in HFD/STZ-induced T2DM mice.

Microwave-Assisted Unidirectional Superconductivity in Al-InAs Nanowire-Al Junctions under Magnetic Fields.

Under certain symmetry-breaking conditions, a superconducting system exhibits asymmetric critical currents, dubbed the "superconducting diode effect." Recently, systems with the ideal superconducting diode efficiency or unidirectional superconductivity have received considerable interest. In this work, we report the study of Al-InAs nanowire-Al Josephson junctions under microwave irradiation and magnetic fields. We observe an enhancement of superconducting diode effect under microwave driving, featured by a horizontal offset of the zero-voltage step in the voltage-current characteristic that increases with microwave power. Devices reach the unidirectional superconductivity regime at sufficiently high driving amplitudes. The offset changes sign with the reversal of the magnetic field direction. Meanwhile, the offset magnitude exhibits a roughly linear response to the microwave power in dBm when both the power and the magnetic field are large. The signatures observed are reminiscent of a recent theoretical proposal using the resistively shunted junction (RSJ) model. However, the experimental results are not fully explained by the RSJ model, indicating a new mechanism for unidirectional superconductivity that is possibly related to nonequilibrium dynamics or dissipation in periodically driven superconducting systems.

Structural characterisation of a novel polysaccharide from pseudostellaria heterophylla fibrous root and its anti-inflammatory and antioxidant activities in vitro.

A novel water-soluble polysaccharide, named PF90-1, with a molecular weight of 1.8 kDa, was isolated and purified from the fibrous root of Pseudostellaria heterophylla. PF90-1 is composed of Gal, Glc and Man in a molar ratio of 73.61: 19.11: 7.28. Methylation analysis revealed that PF90-1 comprises of T-Galp, 1,4-Galp, 1,3,4-Galp, 1,2,3,4-Galp, T-Glcp and 1,3-Manp in a molar ratio of 37.89: 9.37: 17.01: 12.01: 15.88: 7.83. Bioactivity experiments showed that PF90-1 significantly improved lipopolysaccharide (LPS)-induced inflammatory damage in RAW264.7 cells by inhibiting nitric oxide (NO) production and reducing the levels of pro-inflammatory factors (IL-1ß and TNF-α). In addition, PF90-1 exhibited strong antioxidant effects, protecting PC12 cells from H2O2-induced oxidative damage. This findings suggest that PF90-1 holds potential therapeutic value for the treatment of inflammatory and oxidative injuries.

Analysis of placebo effect of acupuncture. / é’ˆåˆºå®‰æ °å‰‚æ•ˆåº”å‰–æž.

Acupuncture is a comprehensive therapy which takes the theory of traditional Chinese medicine as the core. Currently, there is much controversy surrounding the "placebo effect" of acupuncture： some people argue that acupuncture is a "super placebo", while others believe that the so-called placebo effect is just part of the therapeutic effect of acupuncture. To solve the controversy, this article clarified the definition, composition, and research purposes of "placebo acupuncture", pointed out its differences from "sham acupuncture", elucidated the relationship between the placebo effect and the intrinsic efficacy of acupuncture, distinguished the differences between the "observed placebo effect" and the "real placebo effect" in acupuncture clinical trials, and proposed the dilemmas and prospects of implementing "placebo acupuncture" and "sham acupuncture" contrasts at the current stage, in order to provide clues for optimizing randomized controlled trials of acupuncture.

Enlarging effects of microplastics on adsorption, desorption and bioaccessibility of chlorinated organophosphorus flame retardants in landfill soil particle-size fractions.

Chlorinated organophosphorus flame retardants (Cl-OPFRs) and microplastics (MPs) are emerging pollutants in landfills, but their synergistic behaviors and triggering risks were rarely focused on, impeding the resource utilization of landfill soils. This study systematically investigated the adsorption/desorption behaviors, bioaccessibility and human health risks of Cl-OPFRs in landfill soil particle-size fractions coexisted with MPs under simulated gastrointestinal conditions. The results showed that the adsorption capacity and bioaccessibility of Cl-OPFRs in humus soil were higher than that in subsoil. MPs promoted the adsorption of tris(1-chloro-2-methylethyl) phosphate (TCPP) and tris(1,3-dichloro-2-propyl) phosphate (TDCPP) in landfill soils by up to 34.6 % and 34.1 % respectively, but inhibited the adsorption of tris(2-chloroethyl) phosphate (TCEP) by up to 43.6 %. The bioaccessibility of Cl-OPFRs in landfill soils was positively correlated with MPs addition ratio but negatively correlated with the KOW of Cl-OPFRs, soil organic matter and particle size. MPs addition increased the residual concentration of Cl-OPFRs and significantly increased the bioaccessibility of TCEP and TDCPP by up to 33.1 % in landfill soils, resulting in higher carcinogenic and noncarcinogenic risks. The study presents the first series of the combined behavior and effects of MPs and Cl-OPFRs in landfill soils, and provides a theoretical reference for landfill risk management.

Role of lipid droplets in neurodegenerative diseases: From pathogenesis to therapeutics.

Neurodegenerative diseases (NDDs) are a series of disorders characterized by the progressive loss of specific neurons, leading to cognitive and locomotor impairment. NDDs affect millions of patients worldwide but lack effective treatments. Dysregulation of lipids, particularly the accumulation of lipid droplets (LDs), is strongly implicated in the pathogenesis of NDDs. How LDs contribute to the occurrence and development of NDDs, and their potential as therapeutic targets remain to be addressed. In present review, we first introduce the processes of LDs formation, transportation and degradation. We then highlight how the accumulation of LDs contributes to the pathogenesis of NDDs in a cell type-specific manner. Moreover, we discuss currently available methods for detecting LDs and elaborate on LDs-based therapeutic strategies for NDDs. Lastly, we identify gaps that need to be filled to better leverage LD-based theranostics in NDDs and other diseases. We hope this review could shed light on the role of LDs in NDDs and facilitate the development of novel therapeutic strategies for NDDs.

Micafungin protects mouse heart against doxorubicin-induced oxidative injury via suppressing MALT1-dependent k48-linked ubiquitination of Nrf2.

Oxidative stress contributes greatly to doxorubicin (DOX)-induced cardiotoxicity. Down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) is a key factor in DOX-induced myocardial oxidative injury. Recently, we found that mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1)-dependent k48-linked ubiquitination was responsible for down-regulation of myocardial Nrf2 in DOX-treated mice. Micafungin, an antifungal drug, was identified as a potential MALT1 inhibitor. This study aims to explore whether micafungin can reduce DOX-induced myocardial oxidative injury and if its anti-oxidative effect involves a suppression of MALT1-dependent k48-linked ubiquitination of Nrf2. To establish the cardiotoxicity models in vivo and in vitro, mice were treated with a single dose of DOX (15 mg/kg, i.p.) and cardiomyocytes were incubated with DOX (1 µM) for 24 h, respectively. Using mouse model of DOX-induced cardiotoxicity, micafungin (10 or 20 mg/kg) was shown to improve cardiac function, concomitant with suppression of oxidative stress, mitochondrial dysfunction, and cell death in a dose-dependent manner. Similar protective roles of micafungin (1 or 5 µM) were observed in DOX-treated cardiomyocytes. Mechanistically, micafungin weakened the interaction between MALT1 and Nrf2, decreased the k48-linked ubiquitination of Nrf2 while elevated the protein levels of Nrf2 in both DOX-treated mice and cardiomyocytes. Furthermore, MALT1 overexpression counteracted the cardioprotective effects of micafungin. In conclusion, micafungin reduces DOX-induced myocardial oxidative injury via suppression of MALT1, which decreases the k48-linked ubiquitination of Nrf2 and elevates Nrf2 protein levels. Thus, micafungin may be repurposed for treating DOX-induced cardiotoxicity.

Characteristics and release potential of microplastics in municipal solid waste incineration bottom ash.

Incineration is an effective method for reducing and safely treating municipal solid waste. However, microplastics (MPs) inevitably remain in the bottom ash, potentially introducing new pollution risks during subsequent treatment processes. This study conducted an analysis of the accumulation and release potential of MPs in bottom ash samples collected from 4 municipal solid waste incineration plants in Zhejiang, China. The results showed that the abundance of MPs ranged from 20 to 118 items g-1. Remarkably, MPs were found to accumulate predominantly in smaller bottom ash particles below 4.75 mm accounted for up to 70% of the total MPs. Most MPs in the bottom ash were under 100 µm in size, with a majority exceeding 50% being less than 50 µm, typically manifesting as shafts and fibers. In scenarios of secondary crushing, the abundance of MPs increased gradually with the degree of bottom ash crushing. When bottom ash was crushed to a particle size of less than 0.6 mm, the abundance of MPs reached up to 87-901 items g-1, which is 5-10 times higher than the original bottom ash. It is estimated that the annual release of MPs may reach up to 4.05 × 1016 particles. Re-incinerating thoroughly crushed bottom ash at 600 °C successfully decomposed the MPs. Mechanical stress can significantly increase the risk of MPs releasing in bottom ash. This risk can be eliminated by using secondary incineration to achieve complete MPs decomposition.