PUMC-MB1 is a novel group 3 medulloblastoma preclinical model, sensitive to PI3K/mTOR dual inhibitor.

PURPOSE: Medulloblastoma (MB), a common and heterogeneous posterior fossa tumor in pediatric patients, presents diverse prognostic outcomes. To advance our understanding of MB's intricate biology, the development of novel patient tumor-derived culture MB models with necessary data is still an essential requirement. METHODS: We continuously passaged PUMC-MB1 in vitro in order to establish a continuous cell line. We examined the in vitro growth using Cell Counting Kit-8 (CCK-8) and in vivo growth with subcutaneous and intracranial xenograft models. The xenografts were investigated histopathologically with Hematoxylin and Eosin (HE) staining and immunohistochemistry (IHC). Concurrently, we explored its molecular features using Whole Genome Sequencing (WGS), targeted sequencing, and RNA sequecing. Guided by bioinformatics analysis, we validated PUMC-MB1's drug sensitivity in vitro and in vivo. RESULTS: PUMC-MB1, derived from a high-risk MB patient, displayed a population doubling time (PDT) of 48.18 h and achieved 100% tumor growth in SCID mice within 20 days. HE and Immunohistochemical examination of the original tumor and xenografts confirmed the classification of PUMC-MB1 as a classic MB. Genomic analysis via WGS revealed concurrent MYC and OTX2 amplifications. The RNA-seq data classified it within the Group 3 MB subgroup, while according to the WHO classification, it fell under the Non-WNT/Non-SHH MB. Comparative analysis with D283 and D341med identified 4065 differentially expressed genes, with notable enrichment in the PI3K-AKT pathway. Cisplatin, 4-hydroperoxy cyclophosphamide/cyclophosphamide, vincristine, and dactolisib (a selective PI3K/mTOR dual inhibitor) significantly inhibited PUMC-MB1 proliferation in vitro and in vivo. CONCLUSIONS: PUMC-MB1, a novel Group 3 (Non-WNT/Non-SHH) MB cell line, is comprehensively characterized for its growth, pathology, and molecular characteristics. Notably, dactolisib demonstrated potent anti-proliferative effects with minimal toxicity, promising a potential therapeutic avenue. PUMC-MB1 could serve as a valuable tool for unraveling MB mechanisms and innovative treatment strategies.

Preoxidation and Prilling Combined with Doping Strategy to Build High-Performance Recycling Spent LiFePO4 Materials.

Direct regeneration has gained much attention in LiFePO4 battery recycling due to its simplicity, ecofriendliness, and cost savings. However, the excess carbon residues from binder decomposition, conductive carbon, and coated carbon in spent LiFePO4 impair electrochemical performance of direct regenerated LiFePO4. Herein, we report a preoxidation and prilling collaborative doping strategy to restore spent LiFePO4 by direct regeneration. The excess carbon is effectively removed by preoxidation. At the same time, prilling not only reduces the size of the primary particles and shortens the diffusion distance of Li+ but also improves the tap density of the regenerated materials. Besides, the Li+ transmission of the regenerated LiFePO4 is further improved by Ti4+ doping. Compared with commercial LiFePO4, it has excellent low-temperature performance. The collaborative strategy provides a new insight into regenerating high-performance spent LiFePO4.

Serum sodium level fluctuations following the resection of childhood-onset craniopharyngioma.

BACKGROUND: Craniopharyngiomas are low-grade malignancies (WHO I) in the sellar region. Most cases of childhood-onset craniopharyngioma are adamantinomatous craniopharyngioma, and neurosurgery is the treatment of choice. Affected patients have postoperative complications, including water and electrolyte disturbances, because these malignancies develop near the hypothalamus and pituitary gland. Determining postoperative serum sodium fluctuation patterns in these patients can reduce postoperative mortality and improve prognosis. OBJECTIVE: To measure changes in serum sodium levels in pediatric patients who underwent craniopharyngioma surgery and identify influencing factors. METHODS: This retrospective study measured the serum sodium levels of 202 patients aged 0-18 years who underwent craniopharyngioma resection in Beijing Tiantan Hospital and Beijing Children's Hospital and identified predictors of severe hyponatremia and hypernatremia. RESULTS: The mean age of the cohort was 8.35 ± 4.35 years. The prevalence of hypernatremia, hyponatremia, and their severe forms (serum Na+  > 150 mmol/L and serum Na+  < 130 mmol/L) within 14 days after surgery was 66.3%, 72.8%, 37.1%, and 40.6%, respectively. The mean postoperative serum sodium level showed a triphasic pattern, characterized by two peaks separated by a nadir. Sodium levels peaked on days 2 (143.6 ± 7.6 mmol/L) and 14 (143.2 ± 6.7 mmol/L) and reached their lowest on day 6 (135.5 ± 7.5 mmol/L). A total of 31 (15.3%) patients met the diagnostic threshold for hyponatremia and hypernatremia of the triphase response, whereas 116 (57.4%) patients presented this pattern, regardless of met the diagnostic criteria or not. The prevalence of severe hyponatremia varied depending on preoperative endocrine hormone deficiency, tumor status (primary or recurrent), and surgical approach. CONCLUSIONS: Serum sodium levels after craniopharyngioma resection in children showed a triphasic pattern in most cases. The risk of postoperative hyponatremia varied depending on preoperative endocrine hormone deficiency, tumor status (primary or recurrent), and surgical approach.

Nanoporous Nickel Cathode with an Electrostatic Chlorine-Resistant Surface for Industrial Seawater Electrolysis Hydrogen Production.

Seawater electrolysis presents a promising avenue for green hydrogen production toward a carbon-free society. However, the electrode materials face significant challenges including severe chlorine-induced corrosion and high reaction overpotential, resulting in low energy conversion efficiency and low current density operation. Herein, we put forward a nanoporous nickel (npNi) cathode with high chlorine corrosion resistance for energy-efficient seawater electrolysis at industrial current densities (0.4-1 A cm-2). With the merits of an electrostatic chlorine-resistant surface, modulated Ni active sites, and a robust three-dimensional open structure, the npNi electrode showed a low hydrogen evolution reaction overpotential of 310 mV and a high electricity-hydrogen conversion efficiency of 59.7% at 400 mA cm-2 in real seawater and outperformed most Ni-based seawater electrolysis cathodes in recent publications and the commercial Ni foam electrode (459 mV, 46.4%) under the same test condition. In situ electrochemical impedance spectroscopy, high-frame-rate optical microscopy, and first-principles calculation revealed that the improved corrosion resistance, enhanced intrinsic activity, and mass transfer were responsible for the lowered electrocatalytic overpotential and enhanced energy efficiency.

Risk factors for postoperative ventriculoperitoneal shunt requirement in pediatric patients with brain tumors invading or adjacent to CSF circulation pathways.

OBJECTIVE: Hydrocephalus is a common comorbidity of brain tumors in children that may persist following brain tumor resection. This study aimed to explore perioperative risk factors associated with postoperative ventriculoperitoneal shunt (VPS) placement for tumors located at or adjacent to the CSF circulation pathway. METHODS: Patients aged 0-18 years with tumors invading or adjacent to the CSF circulation pathways who underwent brain tumor resection between October 2015 and September 2021 were included in this study. The outcome metric was whether patients underwent VPS placement within 6 months of tumor resection. Patients were followed up every 3-6 months after surgery. Demographic and perioperative imaging characteristics, clinical variables, and long-term treatments, including radiotherapy or chemotherapy, were included in the analysis. RESULTS: Two hundred sixty-five children were included in this study. Of these patients, 38 (14.34%) underwent VPS placement within 6 months of tumor resection. One hundred thirty-two patients (49.81%) presented with preoperative hydrocephalus. Results from the multivariate analysis showed that medulloblastoma (OR 4.15, 95% CI 1.74-9.91, p = 0.001), lateral/third ventricle tumors (OR 4.07, 95% CI 1.33-12.30, p = 0.014), postoperative intraventricular hematoma (OR 3.36, 95% CI 1.53-7.38, p = 0.003), and presence of subdural hygroma in the nonoperated area within 48 hours after tumor resection (OR 2.78, 95% CI 1.15-6.74, p = 0.024) were independent risk factors for postoperative VPS placement. CONCLUSIONS: Postoperative lateral/third ventricle hematoma and subdural hygroma in the nonoperated area, anatomical location, and tumor histology may be potential risk factors for a postoperative VPS after brain tumor resection.

Clinical characteristics and surgical outcomes of low-grade epilepsy-associated brain tumors.

Background: Low-grade epilepsy-associated brain tumors (LEATs) are found to be the second most common lesion-related epilepsy. Malignant potential of LEATs is very low and the overall survival is good, so the focus of treatment is focused more on seizure outcome rather than oncological prognosis. Objectives: This study was conducted to evaluate the risk factors of seizure outcomes after resection in patients with LEATs. Design: A retrospective study. Methods: A retrospective analysis of patients with LEATs who underwent resective surgery in our three epilepsy centers between October 2010 and April 2023 with a minimum follow-up of 1 year. Demography, clinical characters, neurophysiology, and molecular neuropathology were assessed for association with postoperative seizure outcomes at 1-, 2-, and 5-year follow-up. Synthetic minority oversampling technique (SMOTE) algorithm model was performed to handle the imbalance of data distribution. Gaussian Naïve Bayes (GNB) algorithms were created as a basis for classifying outcomes according to observation indicators. Results: A total of 111 patients were enrolled in the cohort. The most common pathology was ganglioglioma (n = 37, 33.3%). The percentage of patients with seizure freedom was 91.0% (101/111) at 1-year follow-up, 87.5% (77/88) at 2-year follow-up, and 79.1% (53/67) at 5-year follow-up. Partial resection had a significantly poor seizure outcome compared to total resection and supratotal resection (p < 0.05). The epileptiform discharge on post-resective intraoperative electrocorticography (ECoG) or postoperative scalp electroencephalography (EEG) were negative factors on postoperative seizure freedom at 1-, 2-, or 5-year follow-ups (p < 0.05). The area under the receiver-operating characteristic curve value of the GNB-SMOTE model was 0.95 (95% CI, 0.876-1.000), 0.892 (95% CI, 0.656-0.934), and 0.786 (95% CI, 0.491-0.937) at 1-, 2-, and 5-year follow-up, respectively. Conclusion: The partial resection, post-resective intraoperative ECoG, and postoperative scalp EEG were valuable indicators of poor seizure outcomes. The utilization of post-resective intraoperative ECoG is beneficial to improve seizure outcomes. Based on the data diversity and completeness of three medical centers, a multivariate correlation analysis model was established based on GNB algorithm.

Ruxolitinib induces apoptosis and pyroptosis of anaplastic thyroid cancer via the transcriptional inhibition of DRP1-mediated mitochondrial fission.

Anaplastic thyroid carcinoma (ATC) has a 100% disease-specific mortality rate. The JAK1/2-STAT3 pathway presents a promising target for treating hematologic and solid tumors. However, it is unknown whether the JAK1/2-STAT3 pathway is activated in ATC, and the anti-cancer effects and the mechanism of action of its inhibitor, ruxolitinib (Ruxo, a clinical JAK1/2 inhibitor), remain elusive. Our data indicated that the JAK1/2-STAT3 signaling pathway is significantly upregulated in ATC tumor tissues than in normal thyroid and papillary thyroid cancer tissues. Apoptosis and GSDME-pyroptosis were observed in ATC cells following the in vitro and in vivo administration of Ruxo. Mechanistically, Ruxo suppresses the phosphorylation of STAT3, resulting in the repression of DRP1 transactivation and causing mitochondrial fission deficiency. This deficiency is essential for activating caspase 9/3-dependent apoptosis and GSDME-mediated pyroptosis within ATC cells. In conclusion, our findings indicate DRP1 is directly regulated and transactivated by STAT3; this exhibits a novel and crucial aspect of JAK1/2-STAT3 on the regulation of mitochondrial dynamics. In ATC, the transcriptional inhibition of DRP1 by Ruxo hampered mitochondrial division and triggered apoptosis and GSDME-pyroptosis through caspase 9/3-dependent mechanisms. These results provide compelling evidence for the potential therapeutic effectiveness of Ruxo in treating ATC.

Quantitative comparison of three thyroidectomy approaches in neck muscles, voice, and swallowing functions.

OBJECTIVE: This study compares endoscopic thyroidectomy by gasless unilateral axillary approach (ETGUA) and sternocleidomastoid leading-edge approach (SLEA) with conventional open thyroidectomy (COT) in hemithyroidectomy. The main focus is on the protection of neck muscles (sternocleidomastoid, omohyoid, sternothyroid) and the postoperative function of voice and swallowing yielded through these common approaches. METHODS: A total of 302 patients who underwent hemithyroidectomy were enrolled and divided into three groups: ETGUA (n = 101), SLEA (n = 100), and COT (n = 101). Ultrasound was used to measure the thickness of bilateral neck muscles, including the sternocleidomastoid, omohyoid, and sternothyroid. The changes in thickness on the surgical side compared to the non-surgical side. Analyzed factors included muscle thickness changes, Swallowing Impairment Score (SIS), Voice Handicap Index (VHI), Scar Cosmesis Assessment and Rating (SCAR), Neck Injury Index (NII), surgery duration, drainage volume, hospitalization, and number of lymph nodes. RESULTS: The clinical characteristics among the three groups were consistent except for differences in sex, age, and BMI. Metrics such as sternocleidomastoid muscle, NII, hypocalcemia, postoperative PTH, transient hoarseness, and number of lymph nodes showed no significant differences among the three groups. However, significant differences were found in the duration of surgery, drainage volume, hospitalization period omohyoid muscle, Sternohyoid muscle, VHI, SIS, and SCAR (all p < 0.001). CONCLUSION: In comparison to COT, ETGUA and SLEA demonstrate superiority in protecting neck muscles and preserving voice and swallowing function without compromising surgical safety or radicality.

Experience in treating children with ocular dyskinesia and hemifacial spasm secondary to pontine tumours adjacent to the fourth ventricle and systematic review.

OBJECTIVE: To investigate the treatment plan and prognosis of children with ocular dyskinesia and hemifacial spasm secondary to pontine tumours adjacent to the fourth ventricle. METHODS: In this retrospective study, the clinical information of 10 consecutively collected children with ocular dyskinesia and hemifacial spasm secondary to pontine tumours adjacent to the fourth ventricle was analyzed. All 10 children underwent pontine tumour resection through a trans-cerebellomedullary fissure approach; 4 children underwent preoperative diffusion tensor imaging scans to determine the relationship between the tumour and facial nerve nucleus, and the other 6 children underwent intraoperative deep electroencephalography (EEG) tumour monitoring, in which the tumour electrical discharge activity of the tumour was recorded. A voxel distribution map was established to describe the distribution of the tumour location, and patient prognosis was evaluated through clinical and imaging follow-up. RESULTS: All 10 children achieved total tumour resection; 9 tumours were pathologically suggested to be ganglioglioma (WHO grade I), and 1 was a hamartoma. The symptoms of the original ocular dyskinesia and hemifacial spasm disappeared immediately after the operation. The children were followed up for 4-75 months, and none of the symptoms recurred; four cases with preoperative diffusion tensor imaging showed that the tumour was close to the facial nerve. Four in six intraoperative electrophysiological monitoring showed that the tumour had electrical discharge behaviour, and the tumour distribution map indicates a high density of tumour presence in the facial nerve nucleus and the nucleus of the abducens nerve. CONCLUSIONS: In paediatric patients, the facial symptoms are related to the location and abnormal electrical discharge of the tumour. There is no significant correlation between ocular dyskinesia and the location of the tumour. Conventional antiepileptic therapy for this disease is ineffective, and early surgical intervention for total tumour resection can achieve a clinical curative effect.

Scrutiny of genome-wide somatic mutation profiles in centenarians identifies the key genomic regions for human longevity.

Somatic mutations accumulate with age and are associated closely with human health, their characterization in longevity cohorts remains largely unknown. Here, by analyzing whole genome somatic mutation profiles in 73 centenarians and 51 younger controls in China, we found that centenarian genomes are characterized by a markedly skewed distribution of somatic mutations, with many genomic regions being specifically conserved but displaying a high function potential. This, together with the observed more efficient DNA repair ability in the long-lived individuals, supports the existence of key genomic regions for human survival during aging, with their integrity being of essential to human longevity.

Postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement in patients with childhood-onset craniopharyngioma.

Objective: Hypothalamic-pituitary axis dysfunction is a common complication in post-operative craniopharyngioma(CP) patients, and it greatly impacts the long-term quality of life of such patients. To better understand the effects of postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement therapy in patients with childhood CP, we assessed approximately 200 patients with childhood-onset CP postoperatively. Methods: Clinical details of patients with childhood-onset CP who underwent sellar tumor resection in Beijing Children's Hospital and Beijing Tiantan Hospital from 2018 to 2019 were retrieved retrospectively. The participants were followed up to assess the effects of post-operative long-term hormone replacement therapy and assess the tumor recurrence rate. Results: The median age of admission was 8.1 (1.8, 14.3) years. Headache (45.5%), visual impairment (39.5%), and nausea (33.0%) were the most common clinical manifestations. ACP accounted for 95% of all CP cases. The incidence of central adrenal insufficiency and central hypothyroidism within the first week after surgery was 56.2% and 70.3%, respectively. At the same time 85.5% of the patients required at least one dose of desmopressin to control urine output. Total survival and tumor recurrence rates were 98.6% and 26.1%, respectively, with a median follow-up time of 29.7 (19.0, 40.3) months. During the follow-up period, 28.1% patients met the diagnostic criteria for short stature, while 54.4% fit the criteria for obesity. In addition, 94.4% of the patients were taking at least one kind of hormone substitution, and 74.7% were taking three or more. The prevalence of levothyroxine, glucocorticoid, desmopressin, and growth hormone replacement therapy was 87.3%, 77.5%, 78.9% and 31.0%, respectively. The proportion of patients treated with the substitutive combination of levothyroxine, hydrocortisone, and desmopressin was 54.9%. Conclusion: This study is a large-sample systematic postoperative endocrine function evaluation of patients with childhood-onset CP. Due to the high prevalence of post-operative hypothalamic-pituitary dysfunction, patients with CP usually require long-term multiple hormone substitution therapy. Individualized management and accurate hormone replacement dosage for postoperative childhood-onset CP patients are of great importance.

Novel Ca-Chelating Peptides from Protein Hydrolysate of Antarctic Krill (Euphausia superba): Preparation, Characterization, and Calcium Absorption Efficiency in Caco-2 Cell Monolayer Model.

Antarctic krill (Euphausia superba) is the world's largest resource of animal proteins and is thought to be a high-quality resource for future marine healthy foods and functional products. Therefore, Antarctic krill was degreased and separately hydrolyzed using flavourzyme, pepsin, papain, and alcalase. Protein hydrolysate (AKH) of Antarctic krill prepared by trypsin showed the highest Ca-chelating rate under the optimized chelating conditions: a pH of 8.0, reaction time of 50 min, temperature of 50 °C, and material/calcium ratio of 1:15. Subsequently, fourteen Ca-chelating peptides were isolated from APK by ultrafiltration and a series of chromatographic methods and identified as AK, EAR, AEA, VERG, VAS, GPK, SP, GPKG, APRGH, GVPG, LEPGP, LEKGA, FPPGR, and GEPG with molecular weights of 217.27, 374.40, 289.29, 459.50, 275.30, 300.36, 202.21, 357.41, 536.59, 328.37, 511.58, 516.60, 572.66, and 358.35 Da, respectively. Among fourteen Ca-chelating peptides, VERG presented the highest Ca-chelating ability. Ultraviolet spectrum (UV), Fourier Transform Infrared (FTIR), and scanning electron microscope (SEM) analysis indicated that the VERG-Ca chelate had a dense granular structure because the N-H, C=O and -COOH groups of VERG combined with Ca2+. Moreover, the VERG-Ca chelate is stable in gastrointestinal digestion and can significantly improve Ca transport in Caco-2 cell monolayer experiments, but phytate could significantly reduce the absorption of Ca derived from the VERG-Ca chelate. Therefore, Ca-chelating peptides from protein hydrolysate of Antarctic krill possess the potential to serve as a Ca supplement in developing healthy foods.

Protective effects of maternal administration of total saponins of Codonopsis pilosula in the mice offspring following diarrhea: role of immune function, antioxidant function, and intestinal inflammatory injury.

Total saponins of Codonopsis (TSC) are a kind of critical bioactive substances in Codonopsis, which have anti-inflammatory, antioxidant, anti-ulcer, immunomodulatory effects, and protective effects on ulcerative enteritis. In this study, TSC (3.75 mL/kg, gavage) was administered once a day to 13-day gestation Kunming mice for 5 days. On day 13 of birth, the offspring were given Escherichia coli solution (0.15 mL/mouse, intraperitoneal injection) and senna leaf decoction (0.15 mL/mouse, gavage) once a day for 6 days. The results showed that gestation maternal administration of TSC effectively reduced the diarrhea index, increased the content of sIgA, IgG, SOD, and GSH, inhibited the TLR4/MyD88/NF-κB pathway in the intestine, reduced the expression of inflammatory factors, and alleviated intestinal injury in the littermates. The results provided a critical reference for the clinical application of TSC to control diarrhea in animal offspring.

Construction of a Preoxidation and Cation Doping Regeneration Strategy to Improve Rate Performance Recycling Spent LiFePO4 Materials.

Efficient recycling of spent lithium-ion batteries (LIBs) is significant for solving environmental problems and promoting resource conservation. Economical recycling of LiFePO4 (LFP) batteries is extremely challenging due to the inexpensive production of LFP. Herein, we report a preoxidation combine with cation doping regeneration strategy to regenerate spent LiFePO4 (SLFP) with severely deteriorated. The binder, conductive agent, and residual carbon in SLFP are effectively removed through preoxidation treatment, which lays the foundation for the uniform and stable regeneration of LFP. Mg2+ doping is adopted to promote the diffusion efficiency of lithium ions, reduces the charge-transfer impedance, and further improves the electrochemical performance of the regenerated LFP. The discharge capacity of SLFP with severe deterioration recovers successfully from 43.2 to 136.9 mA h g-1 at 0.5 C. Compared with traditional methods, this technology is simple, economical, and environment-friendly. It provided an efficient way for recycling SLFP materials.

Electrodeposition-Assisted Crystal Growth Regulation of PdBi Clusters on Carbon Cloths for Ethanol Oxidation.

Carbon-supported Pd-based clusters are one of the most promising anodic catalysts for ethanol oxidation reaction (EOR) due to their encouraging activity and practical applications. However, unclear growth mechanism of Pd-based clusters on the carbon-based materials has hindered their extensive applications. Herein, we first introduce multi-void spherical PdBi cluster/carbon cloth (PdBi/CC) composites by an electrodeposition routine. The growth mechanism of PdBi clusters on the CC supports has been systemically investigated by evaluating the selected samples and tuning their compositions, which involve the big difference in standard redox potential between Pd2+/Pd and Bi3+/Bi and easy adsorption of Bi3+ on the surface of Pd-rich seeds. Benefitting from the ensembles of many nanocrystal subunits, multi-void spherical PdBi clusters can present collective properties and novel functionalities. In addition, the outstanding characteristics of CC supports enable PdBi clusters with stable nanostructures. Thanks to the unique structure, Pd20Bi/CC catalysts manifest higher EOR activity and better stability compared to Pd/CC. Systematic characterizations and a series of CO poisoning tests further confirm that the dramatically enhanced EOR activity and stability can be attributed to the incorporation of Bi species and the strong coupling of the structure between PdBi clusters and CC supports.

A retrospective study comprising 228 cases of pediatric scalp and skull lesions.

BACKGROUND: Most neurosurgery presentations in children present with a mass that may be scalp and skull lesions, including neoplastic and congenital malformed structural lesions, respectively. Clinicians should make early diagnoses and identify cases requiring surgical intervention promptly to help achieve a better prognosis. METHOD: This study retrospectively reviewed studies on children's scalp and skull lesions within a pediatric medical center's department of neurosurgery. The detailed clinical information and pathological types of these cases were scrutinized. RESULT: A total of 228 children's scalp and skull lesions with clinical information and identified histopathology types were summarized. The most common scalp and skull lesions were benign dermoid cysts; malignant types were rare but can occur in children. CONCLUSION: Based on the combined clinical symptoms and image information, children's scalp and skull lesions should be diagnosed early. Malignant scalp and skull lesions/other special cases should be treated seriously.

Confinement Effects in Carbonized ZIF-Confined Hollow PtCo Nanospheres Enable the Methanol Oxidation Reaction.

Confinement effects in highly porous nanostructures can effectively adjust the selectivity and kinetics of electrochemical reactions, which can boost the methanol oxidation reaction (MOR). In this work, carbonized ZIF-8-confined hollow PtCo nanospheres (PtCo@carbonized ZIF-8) were fabricated using a facile strategy. A monodisperse confined region was successfully prepared, and the dispersion of the PtCo nanoparticles (NPs) could be precisely regulated, allowing for the effective tuning of the confined region. Thus, the precise regulation of the catalytic reaction was achieved. Importantly, hollow PtCo NPs were prepared using a method based on the Kirkendall effect, and their forming mechanism was systematically investigated. Because of the confinement effects of carbonized zeolitic imidazolate framework-8 (ZIF-8), the crystal and electronic structures of the PtCo NPs were able to be effectively tuned. Our electrochemical results show that PtCo@carbonized ZIF-8 composites manifest a higher mass activity (1.4 A mgPt-1) and better stability compared to commercial Pt/C.

A defect in mitochondrial fatty acid synthesis impairs iron metabolism and causes elevated ceramide levels.

In most eukaryotic cells, fatty acid synthesis (FAS) occurs in the cytoplasm and in mitochondria. However, the relative contribution of mitochondrial FAS (mtFAS) to the cellular lipidome is not well defined. Here we show that loss of function of Drosophila mitochondrial enoyl coenzyme A reductase (Mecr), which is the enzyme required for the last step of mtFAS, causes lethality, while neuronal loss of Mecr leads to progressive neurodegeneration. We observe a defect in Fe-S cluster biogenesis and increased iron levels in flies lacking mecr, leading to elevated ceramide levels. Reducing the levels of either iron or ceramide suppresses the neurodegenerative phenotypes, indicating an interplay between ceramide and iron metabolism. Mutations in human MECR cause pediatric-onset neurodegeneration, and we show that human-derived fibroblasts display similar elevated ceramide levels and impaired iron homeostasis. In summary, this study identifies a role of mecr/MECR in ceramide and iron metabolism, providing a mechanistic link between mtFAS and neurodegeneration.

Revealing the origin of activity in phthalocyanine-based dual-metal sites towards electrochemical nitric oxide reduction.

Coordinated ligands play crucial roles in tuning the electrochemical nitrate reduction performance of phthalocyanine (Pc)-based dual atom catalysts. With the assistance of axial O ligands, fast NO to NH3 conversion can be realized on O-Ni2-Pc and O-Cu2-Pc. A 2-N product, N2O, can be synthesized on Co2-Pc, Cr2-Pc, O-Co2-Pc, and O-Fe2-Pc through N-N coupling with high NO coverage. ΔENO can be identified as a valid descriptor to support rational M2-Pc design.

Production, identification, in silico analysis, and cytoprotection on H2O2-induced HUVECs of novel angiotensin-I-converting enzyme inhibitory peptides from Skipjack tuna roes.

Background: Exceeding 50% tuna catches are regarded as byproducts in the production of cans. Given the high amount of tuna byproducts and their environmental effects induced by disposal and elimination, the valorization of nutritional ingredients from these by-products receives increasing attention. Objective: This study was to identify the angiotensin-I-converting enzyme (ACE) inhibitory (ACEi) peptides from roe hydrolysate of Skipjack tuna (Katsuwonus pelamis) and evaluate their protection functions on H2O2-induced human umbilical vein endothelial cells (HUVECs). Methods: Protein hydrolysate of tuna roes with high ACEi activity was prepared using flavourzyme, and ACEi peptides were isolated from the roe hydrolysate using ultrafiltration and chromatography methods and identified by ESI/MS and Procise Protein/Peptide Sequencer for the N-terminal amino acid sequence. The activity and mechanism of action of isolated ACEi peptides were investigated through molecular docking and cellular experiments. Results: Four ACEi peptides were identified as WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12), respectively. The affinity of WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) with ACE was -8.590, -9.703, -9.325, and -8.036 kcal/mol, respectively. The molecular docking experiment elucidated that the significant ACEi ability of WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) was mostly owed to their tight bond with ACE's active sites/pockets via hydrophobic interaction, electrostatic force and hydrogen bonding. Additionally, WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) could dramatically elevate the Nitric Oxide (NO) production and bring down endothelin-1 (ET-1) secretion in HUVECs, but also abolish the opposite impact of norepinephrine (0.5 µM) on the production of NO and ET-1. Moreover, WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) could lower the oxidative damage and apoptosis rate of H2O2-induced HUVECs, and the mechanism indicated that they could increase the content of NO and activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) to decrease the generation of reactive oxygen species (ROS) and malondialdehyde (MDA). Conclusion: WGESF (TRP3), IKSW (TRP6), YSHM (TRP9), and WSPGF (TRP12) are beneficial ingredients for healthy products ameliorating hypertension and cardiovascular diseases.