A new strategy of using low-dose caffeic acid carbon nanodots for high resistance to poorly differentiated human papillary thyroid cancer.

Thyroid cancer is one of the most common endocrine malignancies in clinical practice. Traditional surgery and radioactive iodine ablation have poor treatment results for poorly differentiated thyroid cancer, and there is a risk of metastasis and recurrence. In this study, caffeic acid, a natural herbal extract with certain biological activity, has been as precursor to prepare new caffeic acid carbon nanodots via a one-step hydrothermal method. The caffeic acid carbon nanodots retains part of the structure and biological activity of caffeic acid, and have good biocompatibility, water solubility and stability. The construction of the carbon nanodots could effectively improve their bio-absorption rate and the efficacy. In vitro cell experiments showed that low-dose caffeic acid carbon nanodots had a significant inhibitory effect on poorly differentiated papillary thyroid carcinoma BCPAP cells. At low concentrations of 16 µg/mL, the inhibition rate of human thyroid cancer cells BCPAP was ~ 79%. The anti-tumor mechanism was predicted and verified by transcriptome, real-time quantitative PCR and western blot experiments. The caffeic acid carbon nanodots showed to simultaneously downregulate the expression of KRAS, p-BRAF, p-MEK1 and p-ERK1/2, the four continuous key proteins in a MAPK classical signaling pathway. In vivo experiments further confirmed the caffeic acid carbon nanodots could significantly inhibit the tumorigenicity of xenografts in papillary thyroid carcinoma at quite low doses. This piece of work provides a new nanomedicine and therapeutic strategy for highly resistant poorly differentiated papillary thyroid carcinoma.

Adriamycin-induced podocyte injury via the Sema3A/TRPC5/Rac1 pathway.

Podocytopathies encompass kidney diseases where direct or indirect podocyte injury leads to proteinuria or nephrotic syndrome. Although Semaphorin3A (Sema3A) is expressed in podocytes and tubular cells in adult mammalian kidneys and has a common effect on the progression of podocyte injury, its mechanism remains unclear. Previous studies have shown increased Sema3A expression in various glomerulopathies, indicating a gap in understanding its role. In this study, analysis of human data revealed a positive correlation between the levels of urinary Sema3A and Podocalyxin (PCX), suggesting a close relationship between Sema3A and podocyte loss. Furthermore, the impact of Adriamycin on podocytes was investigated. Adriamycin induced podocyte migration and apoptosis, along with an increase in Sema3A expression, all of which were ameliorated by the inhibition of Sema3A. Importantly, TRPC5 was found to increase the overexpression of Sema3A in podocytes. A TRPC5 inhibitor, AC1903, alleviated podocyte migration and apoptosis, inhibiting the formation of lamellar pseudopodia in the podocyte cytoskeleton by lowering the expression of Rac1. Furthermore, AC1903 relieved massive albuminuria and foot process effacement in the kidneys of Adriamycin-treated mice in vivo. In conclusion, our findings suggest that Sema3A may impact the cytoskeletal stability of podocytes through TRPC5 ion channels, mediated by Rac1, ultimately leading to foot process effacement. Notably, AC1903 demonstrates the potential to reverse Adriamycin-induced foot process fusion and urine protein. These results contribute to a deeper understanding of the mechanisms involved in podocytopathies and highlight the therapeutic potential of targeting the Sema3A-TRPC5 pathway.

SENP3 mediates the deSUMOylation and degradation of YAP1 to regulate the progression of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a prevalent malignancy in women, casting a formidable shadow on their well-being. Positioned within the nucleolus, SUMO-specific protease 3 (SENP3) assumes a pivotal role in the realms of development and tumorigenesis. However, the participation of SENP3 in TNBC remains a mystery. Here, we elucidate that SENP3 exerts inhibitory effects on migration and invasion capacities, as well as on the stem cell-like phenotype, within TNBC cells. Further experiments showed that YAP1 is the downstream target of SENP3, and SENP3 regulates tumorigenesis in a YAP1-dependent manner. YAP1 is found to be SUMOylated and SENP3 deconjugates SUMOylated YAP1 and promotes degradation mediated by the ubiquitin-proteasome system. More importantly, YAP1 with a mutation at the SUMOylation site impedes the capacity of wild-type YAP1 in TNBC tumorigenesis. Taken together, our findings firmly establish the pivotal role of SENP3 in the modulation of YAP1 deSUMOylation, unveiling novel mechanistic insight into the important role of SENP3 in the regulation of TNBC tumorigenesis in a YAP1-dependent manner.

Unveiling the effects of environmental factors and Yellow River inputs on the ichthyoplankton community structure in typical bays.

To unravel the effects of environmental factors on fishery resources in the bay, we conducted six biological and environmental surveys in the Laizhou Bay between 2013 and 2020. The findings of our study illuminated several key aspects: (1) The annual discharge of water and sediment from the Yellow River to Laizhou Bay exhibited notable variations, while concurrently, environmental factors including temperature, salinity, and suspended particle matter underwent fluctuations, yet remained within a relatively stable range overall. (2) A total of 8318 eggs and larvae belonging to 10 orders, 16 families, and 19 genera were collected. Significant interannual fluctuations had been documented in the species composition, abundance, and biodiversity of ichthyoplankton. Notably, both Shannon-Wiener diversity index and Pielou evenness index were significantly negatively correlated with suspended particle matter concentration. (3) The water and sediment discharge significantly positively correlated with the number of cold-temperature species. However, the sediment input negatively correlated with the number of continental shelf benthopelagic fish. (4) Redundancy and correlation analyses confirmed the strong link between spatial and temporal distribution of fish communities and environmental factors, with salinity and dissolved oxygen key for ichthyoplankton abundance. Our research offers a scientific foundation for targeted fishery protection and management, which is crucial for preserving the ecological functions of spawning grounds in the bay.

Relationship between the length of macular Bruch's membrane on fundus photograph and myopia occurrence in pre-myopia children aged 3-6 years: A 3-year longitudinal study.

PURPOSE: To evaluate the occurrence and influencing factors of myopia occurrence in pre-myopia children aged 3-6 years. METHODS: This study included 204 pre-myopia (-0.50D-0.50D). The length of macular BM was shorter in Myopia group than that in Non-myopia group (P < 0.001). Baseline SE and the length of macular BM were independent influencing factors which associated with myopia occurrence (OR, 0.031; 95 % CI, 0.008-0.117, P < 0.001 and OR, 0.204; 95 % CI, 0.055-0.763, P = 0.018, respectively) by multivariate binary logistic regression analysis. SE changing process represented the changes of SE, Myopia group had bigger SE changes (P < 0.001). And in the multivariate liner regression analysis, age was the common influencing factor of SE changing process in total participants, Non-myopia group and Myopia group (B = 0.234, P < 0.001; B = 0.078, P = 0.010; B = 0.161, P = 0.046, respectively) CONCLUSIONS: Initial SE and the length of macular BM in pre-myopia children aged 3-6 years were the independent factors of the occurrence of myopia. And initial age was the common factor that associated with SE changing process.

Temporal vascular arcade angle in fundus image was associated with the rate of spherical equivalent refractive error and axial length changes in myopia children with young school age.

PURPOSE: To evaluate temporal vascular arcade angle and its influencing factors in myopic children. METHODS: It was a retrospective study, we reviewed the records of 119 patients aged 6-10 years with myopia (spherical equivalent refractive error (SER) ≤ -0.05D) in the third year of follow-up in Beijing Hyperopia Reserve Research. We measured temporal vascular arcade angles on the fundus photographs and measured 3-year rate of spherical equivalent(D/year) and axial length (AXL) changes(mm/year). RESULTS: Mean age at initial visit was 7.71±1.20 years and mean SER was -1.32±1.09D. Children were divided into two groups according to the refractive status of children at baseline: Myopia onset group (SER>-0.50D at baseline) (n = 107) and Myopia progression group (SER≤-0.50D at baseline) (n = 12). The mean SER in Myopia progression group was much smaller than Myopia onset group (P < 0.001) and mean AXL in Myopia progression group was much longer than Myopia onset group (P = 0.042). AXL (r=-0.320, P < 0.001), SER change rate (r=-0.209, P = 0.022) and AXL change rate (r=-0.232, P = 0.011) were associated with temporal vascular arcade angle in all participants. In Myopia onset group, AXL (r=-0.317, P < 0.001) and AXL change rate (r=-0.190, P = 0.05) were associated with temporal vascular arcade angle. There were no parameters were associated with temporal vascular arcade angle (all P > 0.05) in Myopia progression group. Only AXL (r=-0.306, P = 0.018) was associated with temporal vascular arcade angle in girls while AXL (r=-0.370, P = 0.004), SER change rate (r=-0.317, P = 0.013) and AXL change rate (r=-0.365, P = 0.004) were all associated with the Angle in boys. CONCLUSION: Temporal vascular arcade angle was associated with the rate of SER and AXL changes in myopia onset children, and showed gender differences. These may suggest that lamina cribrosa location has different influencing factors in different genders and different stages of myopia development. Due to the small number of people in Myopia progression group, large sample size studies are still needed in the future.

Antiswelling Photochromic Hydrogels for Underwater Optically Camouflageable Flexible Electronic Devices.

Optical camouflage offers an effective strategy for enhancing the survival chances of underwater flexible electronic devices akin to underwater organisms. Photochromism is one of the most effective methods to achieve optical camouflage. In this study, antiswelling hydrogels with photochromic properties were prepared using a two-step solvent replacement strategy and explored as underwater optically camouflaged flexible electronic devices. The hydrophobic network formed upon polymerization of hydroxyethyl methacrylate (HEMA) ensured that the hydrogels possessed outstanding antiswelling properties. Internetwork hydrogen bonding interactions allowed the hydrogels to exhibit tissue-adaptable mechanical properties and excellent self-bonding capabilities. The introduction of polyoxometalates further enhanced the hydrogels' mechanical and self-bonding properties while imparting photochromic capability. The hydrogels could be rapidly and reversibly colored under 365 nm UV irradiation. The bleaching rate of the colored hydrogels increased with temperature, bleaching within 12 h at 60 °C but maintaining the color for more than 5 days at room temperature. The self-bonding and photochromic properties enabled the hydrogels to be easily assembled into optically camouflaged underwater flexible electronic devices for underwater motion sensing and wireless information transmission. An optically camouflaged strain sensor was first assembled for underwater limb motion sensing. Additionally, an underwater optically camouflaged wireless information exchange device was assembled to enable wireless communication with a smartphone. This work provided an effective strategy for the optical camouflage of underwater flexible electronic devices, presenting opportunities for next-generation underwater hydrogel-based flexible devices.

Oral Piwi-Interacting RNA Delivery Mediated by Green Tea-Derived Exosome-Like Nanovesicles for the Treatment of Aortic Dissection.

Aortic dissection (AD) is a severe cardiovascular disease necessitating active therapeutic strategies for early intervention and prevention. Nucleic acid drugs, known for their potent molecule-targeting therapeutic properties, offer potential for genetic suppression of AD. Piwi-interacting RNAs, a class of small RNAs, hold promise for managing cardiovascular diseases. Limited research on these RNAs and AD exists. This study demonstrates that an antagomir targeting heart-apoptosis-associated piRNA (HAAPIR) effectively regulates vascular remodeling, mitigating AD occurrence and progression through the myocyte enhancer factor 2D (Mef2D) and matrix metallopeptidase 9 (MMP9) pathways. Green tea-derived plant exosome-like nanovesicles (PELNs) are used for oral administration of antagomir. The antagomir-HAAPIR-nanovesicle complex, after purification and optimization, exhibits a high packing rate, while the antagomir is resistant to enzyme digestion. Administered to mice, the complex targets the aortic lesion, reducing AD incidence and improving survival. Moreover, MMP9 and Mef2D expression decrease significantly, inhibiting the phenotypic conversion of human aortic smooth muscle cells. PELNs encapsulate the antagomir-HAAPIR complex, maintaining stability, mediating transport into the bloodstream, and delivering Piwi-interacting RNAs to AD sites. Thus, HAAPIR is a potential target for persistent clinical AD prevention and treatment, and nanovesicle-encapsulated nucleic acids offer a promising cardiovascular disease treatment, providing insights for other therapeutic targets.

Development of an anisotropic polarizable model for the all-atom AMOEBA force field.

For planar and rigid π-conjugated molecular systems, electrostatic and inductive interactions are pivotal in governing molecular packing structures and electron polarization energies. These electrostatic interactions typically exhibit an anisotropic nature within π-conjugated systems. In this study, we utilize the atoms in molecules (AIM) theory in conjunction with linear response theory to decompose molecular polarizability into distributed atomic polarizability tensors. On the basis of atomic polarizability tensors, we extended an anisotropic polarizable model into the AMOEBA polarizable force field. Both anisotropic and isotropic polarizable models in combination with various density functional theory (DFT)-derived atomic multipoles were applied to optimize the experimental crystals of naphthalene and anthracene. Furthermore, these two types of electrostatic models, coupled with the evolutionary algorithm USPEX program, are utilized to predict the crystal structures of oligoacenes. Our findings demonstrate that the anisotropic polarizable model exhibits superior performance in crystal refinement and crystal structure prediction. This enriched anisotropic polarizable model is seamlessly integrated into the AMOEBA polarizable force field and readily applicable within our modified Tinker program.

Epigenetic modifications of gonadotropin receptors can regulate follicular development.

The spatiotemporal transcription of follicle-stimulating hormone receptor (FSHR) and luteinizing hormone/human chorionic gonadotropin receptor (LHCGR) are crucial events for follicular development. However, their regulatory mechanisms are unclear. DNA methylation and histone acetylation are the main epigenetic modifications, and play important roles in transcriptional expression, which regulate cell responses including cell proliferation, senescence and apoptosis. This review will discuss the dynamic epigenetic modifications of FSHR and LHCGR that occur during the process of follicular development and their response to gonadotropins. In addition, some alteration patterns that occur during these epigenetic modifications, as well as their retrospect retrotransposons, which regulate the gene expression levels of FSHR and LHCGR will be discussed.

Concomitant Medications Alter Clinical Outcomes in Patients with Advanced Digestive Tract Cancer Receiving PD-1 Checkpoint Inhibitors Combined with Antiangiogenetic Agents.

PURPOSE: Our study aimed to evaluate the impact of concomitant medications on the response and survival of patients with advanced digestive tract cancer receiving an immunotherapy-antiangiogenesis combination. METHODS: We conducted a three-center observational retrospective study of patients with advanced digestive tract cancer who received programmed death-1 (PD-1) inhibitors plus antiangiogenic agents between March 2019 and July 2022 in China. The patients had one of the three types of primary tumors: hepatocellular carcinoma (HCC), colorectal cancer (CRC), and gastric cancer (GC). RESULTS: The study included 352 patients. The most frequently prescribed co-medications were nonsteroidal anti-inflammatory drugs (NSAIDs) (46.3%), proton pump inhibitors (PPIs) (38.0%), systemic antibiotics (33.8%), and corticosteroids (30.1%). Probiotics had a direct correlation with a higher objective response rate (ORR) (OR 2.4, 95% CI 1.2 to 4.7, p = 0.013). Patients who received PPIs for gastritis/gastroesophageal reflux disease (GERD) (HR 0.7, 95% CI 0.5 to 1.0, p = 0.045), anticoagulants (HR 0.5, 95% CI 0.3 to 0.9, p = 0.009), and probiotics (HR 0.7, 95% CI 0.5 to 1.0, p = 0.034) had longer progression-free survival (PFS). Patients who received PPIs for gastritis/GERD (HR 0.6, 95% CI 0.4 to 0.9; p = 0.009) had longer overall survival (OS), while patients receiving opioids (HR 1.5, 95% CI 1.1 to 2.0, p = 0.010) had a significantly higher risk of death. CONCLUSION: Patients with advanced digestive tract cancer who were administered PPIs for gastritis/GERD indication, anticoagulants, or probiotics in combination with PD-1 inhibitors and antiangiogenic agents experienced improved clinical outcomes. However, opioid administration was linked to reduced OS in patients receiving combined therapy.

ATM, BLM, and CDH1 gene co-mutations in a high-grade endometrial stromal sarcoma patient with multiple abdominal cavity metastases: a case report and literature review.

BACKGROUND: High-grade endometrial stromal sarcoma (HG-ESS) is a rare malignant tumor with poor prognosis. To overcome the limitations of current treatment for advanced patients, the intervention of targeted drug therapy is urgently needed. CASE PRESENTATION: A 74-year-old married woman who presented with abdominal distension and lower abdominal pain was admitted to Hebei General Hospital. After surgery, immunohistochemical staining revealed a malignant tumor which was consistent with HG-ESS. Tumor recurrence occurred 2 months after surgery. Then the patient underwent chemotherapy with two courses but responded poorly. Subsequently we observed ATM, BLM, and CDH1 co-mutations by Next Generation Sequencing (NGS). Then the patient received pamiparib, which resulted in a 10-month progression-free survival (PFS) and is now stable with the administration of sintilimab in combination with pamiparib and anlotinib. CONCLUSIONS: Due to the successful use of poly ADP-ribose polymerase inhibitor (PARPi) on HG-ESS, we suggest that the selection of effective targeted drugs combined with anti- programmed death-1 (PD-1) drug therapy based on genetic testing may become a new option for the treatment of homologous repair deficient (HR-deficient) HG-ESS.

CBP60b clade proteins are prototypical transcription factors mediating immunity.

Transcriptional reprogramming is critical for plant immunity. Several calmodulin (CaM)-binding protein 60 (CBP60) family transcription factors (TFs) in Arabidopsis (Arabidopsis thaliana), including CBP60g, Systemic Acquired Resistance Deficient 1 (SARD1), CBP60a, and CBP60b, are critical for and show distinct roles in immunity. However, there are additional CBP60 members whose function is unclear. We report here that Arabidopsis CBP60c-f, four uncharacterized CBP60 members, play redundant roles with CBP60b in the transcriptional regulation of immunity responses, whose pCBP60b-driven expression compensates the loss of CBP60b. By contrast, neither CBP60g nor SARD1 is inter-changeable with CBP60b, suggesting clade-specific functionalization. We further show that function of CBP60b clade TFs relies on DNA-binding domains (DBDs) and CaM-binding domains, suggesting that they are downstream components of calcium signaling. Importantly, we demonstrate that CBP60s encoded in earliest land plant lineage Physcomitrium patens and Selaginella moellendorffii, are functionally homologous to Arabidopsis CBP60b, suggesting that the CBP60b clade contains the prototype TFs of the CBP60 family. Furthermore, tomato and cucumber CBP60b-like genes rescue the defects of Arabidopsis cbp60b and activate the expression of tomato and cucumber SALICYLIC ACID INDUCTION DEFICIIENT2 (SID2) and ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) genes, suggesting that immune response pathways centered on CBP60b are also evolutionarily conserved. Together, these findings suggest CBP60b clade transcription factors are functionally conserved in evolution and positively mediate immunity.

Lipid droplet accumulation mediates macrophage survival and Treg recruitment via the CCL20/CCR6 axis in human hepatocellular carcinoma.

Metabolic changes play a crucial role in determining the status and function of macrophages, but how lipid reprogramming in macrophages contributes to tumor progression is not yet fully understood. Here, we investigated the phenotype, contribution, and regulatory mechanisms of lipid droplet (LD)-laden macrophages (LLMs) in hepatocellular carcinoma (HCC). Enriched LLMs were found in tumor tissues and were associated with disease progression in HCC patients. The LLMs displayed immunosuppressive phenotypes (with extensive expression of TREM2, PD-L1, CD206, and CD163) and attenuated the antitumor activities of CD8+ T cells. Mechanistically, tumor-induced reshuffling of cellular lipids and TNFα-mediated uptake of tumoral fatty acids contribute to the generation of triglycerides and LDs in macrophages. LDs prolong LLM survival and promote CCL20 secretion, which further recruits CCR6+ Tregs to HCC tissue. Inhibiting LLM formation by targeting DGAT1 and DGAT2, which catalyze the synthesis of triglycerides, significantly reduced Treg recruitment, and delayed tumor growth in a mouse hepatic tumor model. Our results reveal the suppressive phenotypes and mechanisms of LLM enrichment in HCC and suggest the therapeutic potential of targeting LLMs for HCC patients.

Predicting brain edema and outcomes after thrombectomy in stroke: Frontal delta/alpha ratio as an optimal quantitative EEG index.

OBJECTIVE: We aimed to determine whether quantitative electroencephalography (QEEG) measures have predictive value for cerebral edema (CED) and clinical outcomes in acute ischemic stroke (AIS) patients with anterior circulation large vessel occlusion who underwent mechanical thrombectomy (MT). METHODS: A total of 105 patients with AIS in the anterior circulation were enrolled in this prospective study. The occurrence and severity of CED were assessed through computed tomography conducted 24 h after MT. Clinical outcomes were evaluated based on early neurological deterioration (END) and 3-month functional status, as measured by the modified Rankin scale (mRS). Electroencephalography (EEG) recordings were performed 24 h after MT, and QEEG indices were calculated from the standard 16 electrodes and 2 frontal channels (F3-C3, F4-C4). The delta/alpha ratio (DAR), the (delta + theta) / (alpha + beta) ratio (DTABR), and relative delta power were averaged over all electrodes (global) and the F3-C3 and F4-C4 channels (frontal). The predictive effect and value of QEEG indices for CED and clinical outcomes were assessed using ordinal and logistic regression models, as well as receiver operating characteristic (ROC) curves. RESULTS: Significantly, both global and frontal DAR were found to be associated with the severity of CED, END, and poor functional outcomes at 90 days, while global and frontal DTABR and relative delta power were not associated with outcomes. In ROC analysis, the best predictive effect was observed in frontal DAR, with an area under the curve of approximately 0.80. It exhibited approximately 75% sensitivity and 71% specificity for radiological and clinical outcomes when a threshold of 3.3 was used. CONCLUSIONS: QEEG techniques may be considered an efficient bedside monitoring method for assessing treatment efficacy, identifying patients at higher risk of severe CED and END, and predicting long-term functional outcomes. SIGNIFICANCE: QEEG can help identify patients at risk of severe neurological complications that can impact long-term functional recovery in AIS patients who underwent MT.

Role of novel protein acylation modifications in immunity and its related diseases.

The cross-regulation of immunity and metabolism is currently a research hotspot in life sciences and immunology. Metabolic immunology plays an important role in cutting-edge fields such as metabolic regulatory mechanisms in immune cell development and function, and metabolic targets and immune-related disease pathways. Protein post-translational modification (PTM) is a key epigenetic mechanism that regulates various biological processes and highlights metabolite functions. Currently, more than 400 PTM types have been identified to affect the functions of several proteins. Among these, metabolic PTMs, particularly various newly identified histone or non-histone acylation modifications, can effectively regulate various functions, processes and diseases of the immune system, as well as immune-related diseases. Thus, drugs aimed at targeted acylation modification can have substantial therapeutic potential in regulating immunity, indicating a new direction for further clinical translational research. This review summarises the characteristics and functions of seven novel lysine acylation modifications, including succinylation, S-palmitoylation, lactylation, crotonylation, 2-hydroxyisobutyrylation, ß-hydroxybutyrylation and malonylation, and their association with immunity, thereby providing valuable references for the diagnosis and treatment of immune disorders associated with new acylation modifications.

The protective effect of erythropoietin and its novel derived peptides in peripheral nerve injury.

Peripheral nerve injury seriously endangers human life and health, but there is no clinical drug for the treatment of peripheral nerve injury, so it is imperative to develop drugs to promote the repair of peripheral nerve injury. Erythropoietin (EPO) not only has the traditional role of promoting erythropoiesis, but also has a tissue-protective effect. Over the past few decades, researchers have confirmed that EPO has neuroprotective effects. However, side effects caused by long-term use of EPO limited its clinical application. Therefore, EPO derivatives with low side effects have been explored. Among them, ARA290 has shown significant protective effects on the nervous system, but the biggest disadvantage of ARA290, its short half-life, limits its application. To address the short half-life issue, the researchers modified ARA290 with thioether cyclization to generate a thioether cyclized helical B peptide (CHBP). ARA290 and CHBP have promising applications as peptide drugs. The neuroprotective effects they exhibit have attracted continuous exploration of their mechanisms of action. This article will review the research on the role of EPO, ARA290 and CHBP in the nervous system around this developmental process, and provide a certain reference for the subsequent research.

SENP3-regulated Nodal signaling plays a potential role in cardiac left-right asymmetry development.

Congenital heart disease (CHD) is a type of major defect that occurs during embryonic development. Although significant advances have been made in the treatment of CHD, its etiology and molecular mechanism remain unclear. To identify the critical role of SUMOylation in cardiac development, we generated SENP3 knockout mice and showed that SENP3 knockout mice die on embryonic day 8.5 with an open neural tube and reversed left-right cardiac asymmetry. Moreover, SENP3 knockout promoted apoptosis and senescence of H9C2 cells. Further studies showed that Nodal, a critical gene that forms left-right asymmetry, is regulated by SENP3 and that SENP3 regulates cell apoptosis and senescence in a Nodal-dependent manner. Furthermore, Nodal was hyper-SUMOylated after SENP3 knockout, and SUMOylation of Nodal inhibited its ubiquitination and ubiquitin-proteasome degradation pathway. Nodal overexpression enhanced cell apoptosis and senescence; however, the mutation at the SUMOylation site of Nodal reversed its effect on the apoptosis and senescence of H9C2 cells. More importantly, the SENP3-Nodal axis regulates cell senescence by inducing cell autophagy. These results suggest that the SENP3-Nodal signaling axis regulates cardiac senescence-autophagy homeostasis, which in turn affects cardiac development and results in the occurrence of CHD.

Structure and distinct supramolecular organization of a PSII-ACPII dimer from a cryptophyte alga Chroomonas placoidea.

Cryptophyte algae are an evolutionarily distinct and ecologically important group of photosynthetic unicellular eukaryotes. Photosystem II (PSII) of cryptophyte algae associates with alloxanthin chlorophyll a/c-binding proteins (ACPs) to act as the peripheral light-harvesting system, whose supramolecular organization is unknown. Here, we purify the PSII-ACPII supercomplex from a cryptophyte alga Chroomonas placoidea (C. placoidea), and analyze its structure at a resolution of 2.47 Å using cryo-electron microscopy. This structure reveals a dimeric organization of PSII-ACPII containing two PSII core monomers flanked by six symmetrically arranged ACPII subunits. The PSII core is conserved whereas the organization of ACPII subunits exhibits a distinct pattern, different from those observed so far in PSII of other algae and higher plants. Furthermore, we find a Chl a-binding antenna subunit, CCPII-S, which mediates interaction of ACPII with the PSII core. These results provide a structural basis for the assembly of antennas within the supercomplex and possible excitation energy transfer pathways in cryptophyte algal PSII, shedding light on the diversity of supramolecular organization of photosynthetic machinery.