Target recognition and segmentation in turbid water using data from non-turbid conditions: a unified approach and experimental validation.

Semantic segmentation of targets in underwater images within turbid water environments presents significant challenges, hindered by factors such as environmental variability, difficulties in acquiring datasets, imprecise data annotation, and the poor robustness of conventional methods. This paper addresses this issue by proposing a novel joint method using deep learning to effectively perform semantic segmentation tasks in turbid environments, with the practical case of efficiently collecting polymetallic nodules in deep-sea while minimizing damage to the seabed environment. Our approach includes a novel data expansion technique and a modified U-net based model. Drawing on the underwater image formation model, we introduce noise to clear water images to simulate images captured under varying degrees of turbidity, thus providing an alternative to the required data. Furthermore, traditional U-net-based modified models have shown limitations in enhancing performance in such tasks. Based on the primary factors underlying image degradation, we propose a new model which incorporates an improved dual-channel encoder. Our method significantly advances the fine segmentation of underwater images in turbid media, and experimental validation demonstrates its effectiveness and superiority under different turbidity conditions. The study provides new technical means for deep-sea resource development, holding broad application prospects and scientific value.

Visible-Light Cross-Linkable Multifunctional Hydrogels Loaded with Exosomes Facilitate Full-Thickness Skin Defect Wound Healing through Participating in the Entire Healing Process.

The management of severe full-thickness skin defect wounds remains a challenge due to their irregular shape, uncontrollable bleeding, high risk of infection, and prolonged healing period. Herein, an all-in-one OD/GM/QCS@Exo hydrogel was prepared with catechol-modified oxidized hyaluronic acid (OD), methylacrylylated gelatin (GM), and quaternized chitosan (QCS) and loaded with adipose mesenchymal stem cell-derived exosomes (Exos). Cross-linking of the hydrogel was achieved using visible light instead of ultraviolet light irradiation, providing injectability and good biocompatibility. Notably, the incorporation of catechol groups and multicross-linked networks in the hydrogels conferred strong adhesion properties and mechanical strength against external forces such as tensile and compressive stress. Furthermore, our hydrogel exhibited antibacterial, anti-inflammatory, and antioxidant properties along with wound-healing promotion effects. Our results demonstrated that the hydrogel-mediated release of Exos significantly promotes cellular proliferation, migration, and angiogenesis, thereby accelerating skin structure reconstruction and functional recovery during the wound-healing process. Overall, the all-in-one OD/GM/QCS@Exo hydrogel provided a promising therapeutic strategy for the treatment of full-thickness skin defect wounds through actively participating in the entire process of wound healing.

Three-Stage Interpolation Method for Demosaicking Monochrome Polarization DoFP Images.

The emergence of polarization image sensors presents both opportunities and challenges for real-time full-polarization reconstruction in scene imaging. This paper presents an innovative three-stage interpolation method specifically tailored for monochrome polarization image demosaicking, emphasizing both precision and processing speed. The method introduces a novel linear interpolation model based on polarization channel difference priors in the initial two stages. To enhance results through bidirectional interpolation, a continuous adaptive edge detection method based on variance differences is employed for weighted averaging. In the third stage, a total intensity map, derived from the previous two stages, is integrated into a residual interpolation process, thereby further elevating estimation precision. The proposed method undergoes validation using publicly available advanced datasets, showcasing superior performance in both global parameter evaluations and local visual details when compared with existing state-of-the-art techniques.

Combination of ADAM17 knockdown with eplerenone is more effective than single therapy in ameliorating diabetic cardiomyopathy.

Background: The renin-angiotensin-aldosterone system (RAAS) members, especially Ang II and aldosterone, play key roles in the pathogenesis of diabetic cardiomyopathy (DCM). Angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers combined with aldosterone receptor antagonists (mineralocorticoid receptor antagonists) have substantially improved clinical outcomes in patients with DCM. However, the use of the combination has been limited due to its high risk of inducing hyperkalemia. Methods: Type 1 diabetes was induced in 8-week-old male C57BL/6J mice by intraperitoneal injection of streptozotocin at a dose of 55 mg/kg for 5 consecutive days. Adeno-associated virus 9-mediated short-hairpin RNA (shRNA) was used to knock down the expression of ADAM17 in mice hearts. Eplerenone was administered via gavage at 200 mg/kg daily for 4 weeks. Primary cardiac fibroblasts were exposed to high glucose (HG) in vitro for 24 h to examine the cardiac fibroblasts to myofibroblasts transformation (CMT). Results: Cardiac collagen deposition and CMT increased in diabetic mice, leading to cardiac fibrosis and dysfunction. In addition, ADAM17 expression and activity increased in the hearts of diabetic mice. ADAM17 inhibition and eplerenone treatment both improved diabetes-induced cardiac fibrosis, cardiac hypertrophy and cardiac dysfunction, ADAM17 deficiency combined with eplerenone further reduced the effects of cardiac fibrosis, cardiac hypertrophy and cardiac dysfunction compared with single therapy in vivo. High-glucose stimulation promotes CMT in vitro and leads to increased ADAM17 expression and activity. ADAM17 knockdown and eplerenone pretreatment can reduce the CMT of fibroblasts that is induced by high glucose levels by inhibiting TGFß1/Smad3 activation; the combination of the two can further reduce CMT compared with single therapy in vitro. Conclusion: Our findings indicated that ADAM17 knockout could improve diabetes-induced cardiac dysfunction and remodeling through the inhibition of RAAS overactivation when combined with eplerenone treatment, which reduced TGF-ß1/Smad3 pathway activation-mediated CMT. The combined intervention of ADAM17 deficiency and eplerenone therapy provided additional cardiac protection compared with a single therapy alone without disturbing potassium level. Therefore, the combination of ADAM17 inhibition and eplerenone is a potential therapeutic strategy for human DCM.

Effect of sustained measurable residue disease negativity and post-remission treatment selection on the prognosis of acute lymphoblastic leukemia in adults.

BACKGROUND: To explore the effects of monitoring measurable residual disease and post-remission treatment selection on the clinical outcomes of B-cell acute lymphoblastic leukemia (B-ALL) in adults. METHODS: Between September 2010 and January 2022, adult patients with B-ALL who received combination chemotherapy, with or without allogeneic hematopoietic stem cell transplantation (allo-HSCT), were included in the retrospective study, which was approved by the Ethics Committee and the observation of Declaration of Helsinki conditions. RESULTS: One hundred and forty-three B-ALL patients achieved complete remission (CR) were included in the study, of whom 94 patients (65.7%) received allo-HSCT in first complete remission (CR1). Multivariate analysis showed that the most powerful factors affecting OS were transplantation (hazard ratio [HR] = 0.540, p = 0.037) and sustained measurable residue disease (MRD) negativity (HR = 0.508, p = 0.037). The subgroup analysis showed that the prognosis of the allo-HSCT group was better than that of the chemotherapy group, regardless of whether MRD was negative or positive after two courses of consolidation therapy. After consolidation therapy, the prognosis of patients with positive MRD remained significantly better in the allo-HSCT group than in the chemotherapy group. However, no significant difference was observed in the prognosis between the allo-HSCT and chemotherapy groups with negative MRD after consolidation therapy. CONCLUSIONS: B-ALL patients who achieve sustained MRD negativity during consolidation therapy have excellent long-term outcomes even without allo-HSCT. Allo-HSCT is associated with a significant benefit in terms of OS and DFS for patients who were with positive MRD during consolidation therapy.

SorCS2 is involved in promoting periodontitis-induced depression-like behaviour in mice.

BACKGROUND: Emerging evidence supports the association between periodontitis and depression, although the mechanisms are unclear. This study investigated the role of SorCS2 in the pathogenesis of periodontitis-induced depression. MATERIALS AND METHODS: An experimental periodontitis model was established using SorCS2 knockout mice and their wild-type littermates, and depression-like behaviour was evaluated. The expression of proBDNF signalling, neuronal activity, and glutamate-associated signalling pathways were further measured by western blotting and immunofluorescence. In addition, neuroinflammatory status, astrocytic and microglial markers, and the expression of corticosterone-related factors were measured by immunofluorescence, western blotting, and enzyme-linked immunosorbent assays. RESULTS: SorCS2 deficiency alleviated periodontitis-induced depression-like behaviour in mice. Further results suggested that SorCS2 deficiency downregulated the expression of pro-BDNF and glutamate signalling and restored neuronal activities in mice with periodontitis. Neuroinflammation in the mouse hippocampus was triggered by experimental periodontitis but was not affected by SorCS2 deficiency. The levels of corticosterone and the expression of glucocorticoid receptors were also not altered. CONCLUSION: Our study, for the first time, reveals the critical role of SorCS2 in the pathogenesis of periodontitis-induced depression. The underlying mechanism involves proBDNF and glutamate signalling in the hippocampus, providing a novel therapeutic target for periodontitis-associated depression.

Metabolic score for insulin resistance predicts major adverse cardiovascular event in premature coronary artery disease.

BACKGROUND: The Metabolic Score for Insulin Resistance (METS-IR) index serves as a simple surrogate marker for insulin resistance (IR) and is associated with the presence and severity of coronary artery disease (CAD). However, the prognostic significance of METS-IR in patients with premature CAD remains unclear. This study aims to investigate the prognostic value of METS-IR in premature CAD. METHODS: This retrospective study included 582 patients diagnosed with premature CAD between December 2012 and July 2019. The median follow-up duration was 63 months (interquartile range, 44-81 months). The primary endpoint was Major Adverse Cardiovascular Events (MACE), defined as a composite of all-cause death, non-fatal myocardial infarction (MI), repeat coronary artery revascularization, and non-fatal stroke. RESULTS: Patients with MACE had significantly higher METS-IR levels than those without MACE (44.88±8.11 vs. 41.68±6.87, p<0.001). Kaplan-Meier survival curves based on METS-IR tertiles demonstrated a statistically significant difference (log-rank test, p<0.001). In the fully adjusted model, the Hazard Ratio (95% CI) for MACE was 1.41 (1.16-1.72) per SD increase in METS-IR, and the P for trend based on METS-IR tertiles was 0.001 for MACE. Time-dependent Receiver Operator Characteristic (ROC) analysis of METS-IR yielded an Area Under the Curve (AUC) of 0.74 at 2 years, 0.69 at 4 years, and 0.63 at 6 years. CONCLUSIONS: METS-IR serves as a reliable prognostic predictor of MACE in patients with premature CAD. Therefore, METS-IR may be considered a novel, cost-effective, and dependable indicator for risk stratification and early intervention in premature CAD.

Gastrointestinal infections and gastrointestinal haemorrhage are underestimated but serious adverse events in chimeric antigen receptor T-cell recipients: A real-world study.

Chimeric antigen receptor T-cell (CAR-T) therapy has achieved durable response in patients with hematological malignancies, however, therapy-associated multisystem toxicities are commonly observed. Here, we systematically analyzed CAR-T-related gastrointestinal adverse events (GAEs) using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) between January 2017 and December 2021. Disproportionality analyses were performed using reporting odds ratios (ROR) and information component (IC). Among 105,087,611 reports in FAERS, 1518 CAR-T-related GAEs reports were identified. 23 GAEs (n = 281, 18.51%) were significantly overreported following CAR-T therapy compared with the full database, of which 11 GAEs (n = 156, 10.28%) were associated with gastrointestinal infections (GI), such as clostridium difficile colitis (n = 44 [2.90%], ROR = 5.55), enterovirus infection (n = 23 [1.52%], ROR = 20.02), and mucormycosis (n = 15 [0.99%], ROR = 3.09). Overall, the fatality rate of 11 GI-related AEs was 29.49%, especially mucormycosis causing substantial mortality with 60%. In addition, 4 of 23 overreported GAEs were related to haemorrhage and the mortality of gastrointestinal haemorrhage was 73.17%. Lastly, 29 death-related GAEs were identified. These findings could help clinicians early alert those rarely reported but lethal GAEs, thus reducing the risk of severe toxicities.

Ionic Liquid-Enhanced Assembly of Nanomaterials for Highly Stable Flexible Transparent Electrodes.

The controlled assembly of nanomaterials has demonstrated significant potential in advancing technological devices. However, achieving highly efficient and low-loss assembly technique for nanomaterials, enabling the creation of hierarchical structures with distinctive functionalities, remains a formidable challenge. Here, we present a method for nanomaterial assembly enhanced by ionic liquids, which enables the fabrication of highly stable, flexible, and transparent electrodes featuring an organized layered structure. The utilization of hydrophobic and nonvolatile ionic liquids facilitates the production of stable interfaces with water, effectively preventing the sedimentation of 1D/2D nanomaterials assembled at the interface. Furthermore, the interfacially assembled nanomaterial monolayer exhibits an alternate self-climbing behavior, enabling layer-by-layer transfer and the formation of a well-ordered MXene-wrapped silver nanowire network film. The resulting composite film not only demonstrates exceptional photoelectric performance with a sheet resistance of 9.4 Ω sq-1 and 93% transmittance, but also showcases remarkable environmental stability and mechanical flexibility. Particularly noteworthy is its application in transparent electromagnetic interference shielding materials and triboelectric nanogenerator devices. This research introduces an innovative approach to manufacture and tailor functional devices based on ordered nanomaterials.

Electrospun Biomimetic Periosteum Capable of Controlled Release of Multiple Agents for Programmed Promoting Bone Regeneration.

The effective repair of large bone defects remains a major challenge due to its limited self-healing capacity. Inspired by the structure and function of the natural periosteum, an electrospun biomimetic periosteum is constructed to programmatically promote bone regeneration using natural bone healing mechanisms. The biomimetic periosteum is composed of a bilayer with an asymmetric structure in which an aligned electrospun poly(ε-caprolactone)/gelatin/deferoxamine (PCL/GEL/DFO) layer mimics the outer fibrous layer of the periosteum, while a random coaxial electrospun PCL/GEL/aspirin (ASP) shell and PCL/silicon nanoparticles (SiNPs) core layer mimics the inner cambial layer. The bilayer controls the release of ASP, DFO, and SiNPs to precisely regulate the inflammatory, angiogenic, and osteogenic phases of bone repair. The random coaxial inner layer can effectively antioxidize, promoting cell recruitment, proliferation, differentiation, and mineralization, while the aligned outer layer can promote angiogenesis and prevent fibroblast infiltration. In particular, different stages of bone repair are modulated in a rat skull defect model to achieve faster and better bone regeneration. The proposed biomimetic periosteum is expected to be a promising candidate for bone defect healing.

Manganese induces neuronal apoptosis by activating mTOR signaling pathway in vitro and in vivo.

Manganese (Mn) is a well-known environmental pollutant and occupational toxicant that causes neurotoxicity, which present as neurodegenerative-like symptoms. However, the mechanism of Mn-induced neuronal injury remains unclear. In this research, we explored the mechanism of Mn-induced neurotoxicity, focusing on the mTOR signaling pathway. A plasmid expressing a short hairpin RNA (shRNA) targeting mTOR (shRNA-mTOR) was transfected into N27 cells in vitro, and rapamycin was used as an mTOR inhibitor in vivo to block the mTOR signaling pathway. Cells were treated with different concentrations of manganese (II) chloride (MnCl2). We found that Mn induced cell injury and apoptosis and markedly upregulated the expression of mTOR pathway-related proteins. The phosphorylation of 4E-BP1, S6K1, Akt and SGK1 was markedly decreased after blocking mTOR, and cell apoptosis was also reduced. Furthermore, the mTOR-specific inhibitor rapamycin restored learning and memory abilities in vivo. This research highlights that inhibiting mTOR might be useful for preventing Mn-induced neurodegenerative-like disorders.

Paraspeckle protein NONO attenuates vascular calcification by inhibiting bone morphogenetic protein 2 transcription.

Vascular calcification is a pathological process commonly associated with atherosclerosis, chronic kidney disease, and diabetes. Paraspeckle protein NONO is a multifunctional RNA/DNA binding protein involved in many nuclear biological processes but its role in vascular calcification remains unclear. Here, we observed that NONO expression was decreased in calcified arteries of mice and patients with CKD. We generated smooth muscle-specific NONO-knockout mice and established three different mouse models of vascular calcification by means of 5/6 nephrectomy, adenine diet to induce chronic kidney failure, or vitamin D injection. The knockout mice were more susceptible to the development of vascular calcification relative to control mice, as verified by an increased calcification severity and calcium deposition. Likewise, aortic rings from knockout mice showed more significant vascular calcification than those from control mice ex vivo. In vitro, NONO deficiency aggravated high phosphate-induced vascular smooth muscle cell osteogenic differentiation and apoptosis, whereas NONO overexpression had a protective effect. Mechanistically, we demonstrated that the regulation of vascular calcification by NONO was mediated by bone morphogenetic protein 2 (BMP2). NONO directly bound to the BMP2 promoter using its C-terminal region, exerting an inhibitory effect on the transcription of BMP2. Thus, our study reveals that NONO is a novel negative regulator of vascular calcification, which inhibits osteogenic differentiation of vascular smooth muscle cell and vascular calcification via negatively regulating BMP2 transcription. Hence, NONO may provide a promising target for the prevention and treatment of vascular calcification.

Comparison of seven surrogate insulin resistance indexes for prediction of incident coronary heart disease risk: a 10-year prospective cohort study.

Background: There were seven novel and easily accessed insulin resistance (IR) surrogates established, including the Chinese visceral adiposity index (CVAI), the visceral adiposity index (VAI), lipid accumulation product (LAP), triglyceride glucose (TyG) index, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC) and TyG-waist to height ratio (TyG-WHtR). We aimed to explore the association between the seven IR surrogates and incident coronary heart disease (CHD), and to compare their predictive powers among Chinese population. Methods: This is a 10-year prospective cohort study conducted in China including 6393 participants without cardiovascular disease (CVD) at baseline. We developed Cox regression analyses to examine the association of IR surrogates with CHD (hazard ratio [HR], 95% confidence intervals [CI]). Moreover, the receiver operating characteristic (ROC) curve was performed to compare the predictive values of these indexes for incident CHD by the areas under the ROC curve (AUC). Results: During a median follow-up period of 10.25 years, 246 individuals newly developed CHD. Significant associations of the IR surrogates (excepted for VAI) with incident CHD were found in our study after fully adjustment, and the fifth quintile HRs (95% CIs) for incident CHD were respectively 2.055(1.216-3.473), 1.446(0.948-2.205), 1.753(1.099-2.795), 2.013(1.214-3.339), 3.169(1.926-5.214), 2.275(1.391-3.719) and 2.309(1.419-3.759) for CVAI, VAI, LAP, TyG, TyG-BMI, TyG-WC and TyG-WHtR, compared with quintile 1. Furthermore, CVAI showed maximum predictive capacity for CHD among these seven IR surrogates with the largest AUC: 0.632(0.597,0.667). Conclusion: The seven IR surrogates (excepted for VAI) were independently associated with higher prevalence of CHD, among which CVAI is the most powerful predictor for CHD incidence in Chinese populations.

Gsα Regulates Macrophage Foam Cell Formation During Atherosclerosis.

BACKGROUND: Many cardiovascular pathologies are induced by signaling through G-protein-coupled receptors via Gsα (G protein stimulatory α subunit) proteins. However, the specific cellular mechanisms that are driven by Gsα and contribute to the development of atherosclerosis remain unclear. METHODS: High-throughput screening involving data from single-cell and bulk sequencing were used to explore the expression of Gsα in atherosclerosis. The differentially expression and activity of Gsα were analyzed by immunofluorescence and cAMP measurements. Macrophage-specific Gsα knockout (Mac-GsαKO) mice were generated to study the effect on atherosclerosis. The role of Gsα was determined by transplanting bone marrow and performing assays for foam cell formation, Dil-ox-LDL (oxidized low-density lipoprotein) uptake, chromatin immunoprecipitation, and luciferase reporter assays. RESULTS: ScRNA-seq showed elevated Gnas in atherosclerotic mouse aorta's cholesterol metabolism macrophage cluster, while bulk sequencing confirmed increased GNAS expression in human plaque macrophage content. A significant upregulation of Gsα and active Gsα occurred in macrophages from human and mouse plaques. Ox-LDL could translocate Gsα from macrophage lipid rafts in short-term and promote Gnas transcription through ERK1/2 activation and C/EBPß phosphorylation via oxidative stress in long-term. Atherosclerotic lesions from Mac-GsαKO mice displayed decreased lipid deposition compared with those from control mice. Additionally, Gsα deficiency alleviated lipid uptake and foam cell formation. Mechanistically, Gsα increased the levels of cAMP and transcriptional activity of the cAMP response element binding protein, which resulted in increased expression of CD36 and SR-A1. In the translational experiments, inhibiting Gsα activation with suramin or cpGN13 reduced lipid uptake, foam cell formation, and the progression of atherosclerotic plaques in mice in vivo. CONCLUSIONS: Gsα activation is enhanced during atherosclerotic progression and increases lipid uptake and foam cell formation. The genetic or chemical inactivation of Gsα inhibit the development of atherosclerosis in mice, suggesting that drugs targeting Gsα may be useful in the treatment of atherosclerosis.

Association between the triglyceride-glucose index and impaired cardiovascular fitness in non-diabetic young population.

BACKGROUND: The triglyceride-glucose (TyG) index has been linked to the onset, progression, and prognosis of cardiovascular disease (CVD) in middle-aged and elderly individuals. Nevertheless, the relationship between the TyG index and impaired cardiovascular fitness (CVF) remains unexplored in non-diabetic young population. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) study (1999-2004) to conduct a cross-sectional study of 3364 participants who completed an examination of CVF. Impaired CVF was defined as low and moderate CVF levels determined by estimated maximal oxygen consumption (Vo2max), based on sex- and age-specific criteria. The TyG index was calculated by [Formula: see text]. RESULTS: The age (median with interquartile range) of the study population was 28 (19-37) years, and the TyG index (median ± standard deviation) was 8.36 ± 0.52. A significant association between the TyG index and impaired CVF was found in multivariable logistical regression analysis (per 1-unit increase in the TyG index: OR, 1.46; 95% Cl 1.13-1.90). A dose‒response relationship between the TyG index and impaired CVF was presented by restricted cubic splines (RCS). A significant interaction (p = 0.027) between sex and the TyG index for impaired CVF was found in the population aged < 20 years. CONCLUSIONS: In non-diabetic young population, individuals with higher TyG index values are at an increased likelihood of encountering impaired CVF. Furthermore, sex may exert an impact on CVF, as males tend to be more susceptible to impaired CVF under comparable TyG index conditions.

Prevalence, characteristics and significant predictors for cardiovascular disease of patients with preserved ratio impaired spirometry: A 10-year prospective cohort study in China.

BACKGROUND AND OBJECTIVE: Patients with preserved ratio impaired spirometry (PRIsm) have higher incidence rate of cardiovascular disease (CVD). However, few studies focused on PRIsm in China. We determined the prevalence and characteristics of patients with PRIsm in Chinese population. We also aimed to investigate the significant predictive factors of CVD in PRIsm patients. METHODS: In total, 6994 subjects aged from 35 to 70 years old and free of CVD at baseline were categorized into normal (n = 3895), PRIsm (the ratio of forced expired volume in the first second (FEV1) to forced vital capacity (FVC) ≥0.7 and FEV1 <80 % predicted; n = 1997) and obstructive spirometry (FEV1:FVC<0.7; n = 1102). Cox proportional hazards multivariable regression was performed to investigate how baseline characteristics impact CVD incidence. RESULTS: In participants with PRIsm, men had a 0.68-fold higher risk of CVD incidence than women (HR, 1.68; 95%CI, 1.09-2.59; p = 0.020). Our study showed that the rate of CVD incidence increased by 6.0 % with every year's increase in age (HR, 1.06; 95%CI, 1.04-1.09; p < 0.001). A 0.1 increase in FEV1/FVC was significantly associated with a 23.0 % decrease in CVD incidence (HR, 0.77; 95%CI, 0.61-0.97; p = 0.028). Family history of CVD greatly increased the risk of cardiovascular disease incidence (HR, 1.83; 95%CI, 1.18-2.83; p = 0.007). Higher BMI was also a significant risk factor of CVD incidence (HR, 1.06; 95%CI, 1.01-1.10; p = 0.013). CONCLUSION: The prevalence of PRIsm in China was high. PRIsm subjects should be monitored carefully, especially for the older, male, those with higher BMI, lower FEV1/FVC and family history of CVD.

Alterations in mitochondrial structure and function in response to environmental temperature changes in Apostichopus japonicus.

Global temperatures have risen as a result of climate change, and the resulting warmer seawater will exert physiological stresses on many aquatic animals, including Apostichopus japonicus. It has been suggested that the sensitivity of aquatic poikilothermal animals to climate change is closely related to mitochondrial function. Therefore, understanding the interaction between elevated temperature and mitochondrial functioning is key to characterizing organisms' responses to heat stress. However, little is known about the mitochondrial response to heat stress in A. japonicus. In this work, we investigated the morphological and functional changes of A. japonicus mitochondria under three representative temperatures, control temperature (18 °C), aestivation temperature (25 °C) and heat stress temperature (32 °C) temperatures using transmission electron microscopy (TEM) observation of mitochondrial morphology combined with proteomics and metabolomics techniques. The results showed that the mitochondrial morphology of A. japonicus was altered, with decreases in the number of mitochondrial cristae at 25 °C and mitochondrial lysis, fracture, and vacuolization at 32 °C. Proteomic and metabolomic analyses revealed 103 differentially expressed proteins and 161 differential metabolites at 25 °C. At 32 °C, the levels of 214 proteins and 172 metabolites were significantly altered. These proteins and metabolites were involved in the tricarboxylic acid (TCA) cycle, substance transport, membrane potential homeostasis, anti-stress processes, mitochondrial autophagy, and apoptosis. Furthermore, a hypothetical network of proteins and metabolites in A. japonicus mitochondria in response to temperature changes was constructed based on proteomic and metabolomic data. These results suggest that the dynamic regulation of mitochondrial energy metabolism, resistance to oxidative stress, autophagy, apoptosis, and mitochondrial morphology in A. japonicus may play important roles in the response to elevated temperatures. In summary, this study describes the response of A. japonicus mitochondria to temperature changes from the perspectives of morphology, proteins, and metabolites, which provided a better understanding the mechanisms of mitochondrial regulation under environment stress in marine echinoderms.

NIR-Light-Triggered Mild-Temperature Hyperthermia to Overcome the Cascade Cisplatin Resistance for Improved Resistant Tumor Therapy.

Currently, cisplatin resistance has been recognized as a multistep cascade process for its clinical chemotherapy failure. Hitherto, it remains challenging to develop a feasible and promising strategy to overcome the cascade drug resistance (CDR) issue for achieving fundamentally improved chemotherapeutic efficacy. Herein, a novel self-assembled nanoagent is proposed, which is constructed by Pt(IV) prodrug, cyanine dye (cypate), and gadolinium ion (Gd3+), for systematically conquering the cisplatin resistance by employing near-infrared (NIR) light activated mild-temperature hyperthermia in tumor targets. The proposed nanoagents exhibit high photostability, GSH/H+-responsive dissociation, preferable photothermal conversion, and enhanced cellular uptake performance. In particular, upon 785-nm NIR light irradiation, the generated mild temperature of ≈ 43 °C overtly improves the cell membrane permeability and drug uptake, accelerates the disruption of intracellular redox balance, and apparently enhances the formation of Pt-DNA adducts, thereby effectively overcoming the CDR issue and achieves highly improved therapeutic efficacy for cisplatin-resistant tumor ablation.