G protein subunit alpha i2's pivotal role in angiogenesis.

Here we explored the potential role of Gαi2 (G protein subunit alpha i2) in endothelial cell function and angiogenesis. Methods: Genetic methodologies such as shRNA, CRISPR/Cas9, dominant negative mutation, and overexpression were utilized to modify Gαi2 expression or regulate its function. Their effects on endothelial cell functions were assessed in vitro. In vivo, the endothelial-specific Gαi2 shRNA adeno-associated virus (AAV) was utilized to silence Gαi2 expression. The impact of this suppression on retinal angiogenesis in control mice and streptozotocin (STZ)-induced diabetic retinopathy (DR) mice was analyzed. Results: Analysis of single-cell RNA sequencing data revealed Gαi2 (GNAI2) was predominantly expressed in retinal endothelial cells and expression was increased in retinal endothelial cells following oxygen-induced retinopathy (OIR) in mice. Moreover, transcriptome analysis linking Gαi2 to angiogenesis-related processes/pathways, supported by increased Gαi2 expression in experimental OIR mouse retinas, highlighted its possible role in angiogenesis. In various endothelial cell types, shRNA-induced silencing and CRISPR/Cas9-mediated knockout (KO) of Gαi2 resulted in substantial reductions in cell proliferation, migration, invasion, and capillary tube formation. Conversely, Gαi2 over-expression in endothelial cells induced pro-angiogenic activities, enhancing cell proliferation, migration, invasion, and capillary tube formation. Furthermore, our investigation revealed a crucial role of Gαi2 in NFAT (nuclear factor of activated T cells) activation, as evidenced by the down-regulation of NFAT-luciferase reporter activity and pro-angiogenesis NFAT-targeted genes (Egr3, CXCR7, and RND1) in Gαi2-silenced or -KO HUVECs, which were up-regulated in Gαi2-overexpressing endothelial cells. Expression of a dominant negative Gαi2 mutation (S48C) also down-regulated NFAT-targeted genes, slowing proliferation, migration, invasion, and capillary tube formation in HUVECs. Importantly, in vivo experiments revealed that endothelial Gαi2 knockdown inhibited retinal angiogenesis in mice, with a concomitant down-regulation of NFAT-targeted genes in mouse retinal tissue. In contrast, Gαi2 over-expression in endothelial cells enhanced retinal angiogenesis in mice. Single-cell RNA sequencing data confirmed increased levels of Gαi2 specifically in retinal endothelial cells of mice with streptozotocin (STZ)-induced diabetic retinopathy (DR). Importantly, endothelial Gαi2 silencing ameliorated retinal pathological angiogenesis in DR mice. Conclusion: Our study highlights a critical role for Gαi2 in NFAT activation, endothelial cell activation and angiogenesis, offering valuable insights into potential therapeutic strategies for modulating these processes.

Aging and comprehensive molecular profiling in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aging-related and heterogeneous hematopoietic malignancy. In this study, a total of 1,474 newly diagnosed AML patients with RNA sequencing data were enrolled, and targeted or whole exome sequencing data were obtained in 94% cases. The correlation of aging-related factors including age and clonal hematopoiesis (CH), gender, and genomic/transcriptomic profiles (gene fusions, genetic mutations, and gene expression networks or pathways) was systematically analyzed. Overall, AML patients aged 60 y and older showed an apparently dismal prognosis. Alongside age, the frequency of gene fusions defined in the World Health Organization classification decreased, while the positive rate of gene mutations, especially CH-related ones, increased. Additionally, the number of genetic mutations was higher in gene fusion-negative (GF-) patients than those with GF. Based on the status of CH- and myelodysplastic syndromes (MDS)-related mutations, three mutant subgroups were identified among the GF- AML cohort, namely, CH-AML, CH-MDS-AML, and other GF- AML. Notably, CH-MDS-AML demonstrated a predominance of elderly and male cases, cytopenia, and significantly adverse clinical outcomes. Besides, gene expression networks including HOXA/B, platelet factors, and inflammatory responses were most striking features associated with aging and poor prognosis in AML. Our work has thus unraveled the intricate regulatory circuitry of interactions among different age, gender, and molecular groups of AML.

Dual-site segmentally synergistic catalysis mechanism: boosting CoFeSx nanocluster for sustainable water oxidation.

Efficient oxygen evolution reaction electrocatalysts are essential for sustainable clean energy conversion. However, catalytic materials followed the conventional adsorbate evolution mechanism (AEM) with the inherent scaling relationship between key oxygen intermediates *OOH and *OH, or the lattice-oxygen-mediated mechanism (LOM) with the possible lattice oxygen migration and structural reconstruction, which are not favorable to the balance between high activity and stability. Herein, we propose an unconventional Co-Fe dual-site segmentally synergistic mechanism (DSSM) for single-domain ferromagnetic catalyst CoFeSx nanoclusters on carbon nanotubes (CNT) (CFS-ACs/CNT), which can effectively break the scaling relationship without sacrificing stability. Co3+ (L.S, t2g6eg0) supplies the strongest OH* adsorption energy, while Fe3+ (M.S, t2g4eg1) exposes strong O* adsorption. These dual-sites synergistically produce of Co-O-O-Fe intermediates, thereby accelerating the release of triplet-state oxygen ( ↑ O = O ↑ ). As predicted, the prepared CFS-ACs/CNT catalyst exhibits less overpotential than that of commercial IrO2, as well as approximately 633 h of stability without significant potential loss.

A novel approach for transforming breast cancer stem cells into endothelial cells.

Tumor vascular endothelial cells play a pivotal in the tumor microenvironment, influencing the proliferation, invasion, and metastasis of tumor progression. The present study investigated a novel method for inducing the transformation of breast cancer stem cells into endothelial cells, providing a cellular model investigating anti-angiogenic mechanisms in vitro. The breast cancer cell line MCF-7 was used, and the expression of CD133 was initially detected using flow cytometry. CD133+ breast cancer cells were purified using immunomagnetic bead sorting technology, yielding an MCF-7CD133+ subpopulation. The proliferation ability of these cells was assessed using an MTT assay, while their microsphere formation ability was evaluated using a microsphere formation assay. Post-transformation in an optimized endothelial cell culture medium, expression of endothelial cell markers CD31 and CD105 were detected using flow cytometry. Endothelial cell tube formation assays and DiI-labeled acetylated low-density lipoprotein (DiI-Ac-LDL) assays were employed to analyze the endothelial cell function of the MCF-7CD133+ cells. MDM2/CEN12 gene amplification was detected through fluorescence in situ hybridization (FISH). The MCF-7 breast cancer cell line exhibited 1.7±0.3% trace cells expressing the stem cell surface marker CD133. After anti-CD133 immunomagnetic bead sorting, MCF-7CD133+ and MCF-7CD133- subpopulation cells were obtained, with CD133 expression rates of 85.6±2.8 and 0.18±0.08%, respectively. MTT assay results demonstrated that, after 7 days, the proliferation rate of MCF-7CD133+ cells was significantly higher compared with MCF-7CD133- cells. MCF-7CD133+ subpopulation cells displayed strong stem cell characteristics, growing in suspension in serum-free media and forming tumor cell spheres. In contrast, MCF-7CD133- cells failed to form microspheres. After culturing cells in endothelial cell differentiation and maintenance media, the percentage of MCF-7CD133+ cells before and after endothelial cell culture was 0.3±0.16 and 81.4±8.37% for CD31+ cells and 0.2±0.08 and 83.8±7.24% for CD105+ cells, respectively. Vascular-like structure formation and Ac-LDL phagocytosis with red fluorescence in the tube formation assays confirmed endothelial cell function in the MCF-7CD133+ cells. FISH was used to verify MDM2/CEN12 gene amplification in the induced MCF-7CD133+ cells, indicating tumor cell characteristics. The modified endothelial cell transformation medium effectively induced differentiated tumor stem cells to express vascular endothelial cell markers and exhibit endothelial functions, ideal for in vitro anti-angiogenesis research.

Diagnostic value of circRNA in coronary heart disease: a meta-analysis.

Aim: Studies have indicated that circRNAs have diagnostic value for coronary heart disease (CHD), but the efficacy varies greatly; therefore, a meta-analysis was conducted to assess the diagnostic value of circRNAs in CHD. Materials & methods: 16 studies with 3962 subjects (2239 cases and 1723 controls) were included by searching PubMed, Web of Science and MEDLINE. The pooled sensitivity and specificity, summary receiver operating characteristic and area under the curve, positive likelihood ratio and negative likelihood ratio were calculated. Results: The pooled area under the curve of circRNAs for the diagnosis of CHD was 0.80 (sensitivity and specificity were 0.77 and 0.68, respectively), and more indexes were calculated. Conclusion: circRNAs may be good biomarkers for diagnosing CHD.

Unconventional Bilateral Compressive Strained Ni-Ir Interface Synergistically Accelerates Alkaline Hydrogen Oxidation.

The alkaline hydrogen oxidation reaction (HOR) involves the coupling of adsorbed hydrogen (Had) and hydroxyl (OHad) species and is thus orders of magnitude slower than that in acid media. According to the Sabatier principle, developing electrocatalysts with appropriate binding energy for both intermediates is vital to accelerating the HOR though it is still challenging. Herein, we propose an unconventional bilateral compressive strained Ni-Ir interface (Ni-Ir(BCS)) as efficient synergistic HOR sites. Density functional theory (DFT) simulations reveal that the bilateral compressive strain effect leads to the appropriate adsorption for both Had and OHad, enabling their coupling thermodynamically spontaneous and kinetically preferential. Such Ni-Ir(BCS) is experimentally achieved by embedding sub-nanometer Ir clusters in graphene-loaded high-density Ni nanocrystals (Ni-Ir(BCS)/G). As predicted, it exhibits a HOR mass activity of 7.95 and 2.88 times those of commercial Ir/C and Pt/C together with much enhanced CO tolerance, respectively, ranking among the most active state-of-the-art HOR catalysts. These results provide new insights into the rational design of advanced electrocatalysts involving coordinated adsorption and activation of multiple reactants.

Monomicelle-Directed Engineering of Strained Carbon Nanoribbons as Oxygen Reduction Catalyst.

To date, precisely tailoring local active sites of well-defined earth-abundant metal-free carbon-based electrocatalysts for attractive electrocatalytic oxygen reduction reaction (ORR), remains challenging. Herein, the authors successfully introduce a strain effect on active C-C bonds adjacent to edged graphitic nitrogen (N), which raises appropriate spin-polarization and charge density of carbon active sites and kinetically favor the facilitation of O2 adsorption and the activation of O-containing intermediates. Thus, the constructed metal-free carbon nanoribbons (CNRs-C) with high-curved edges exhibit outstanding ORR activity with half-wave potentials of 0.78 and 0.9 V in 0.5 m H2 SO4 and 0.1 m KOH, respectively, overwhelming the planar one (0.52 and 0.81 V) and the N-doped carbon sheet (0.41 and 0.71 V). Especially in acidic media, the kinetic current density (Jk ) is 18 times higher than that of the planar one and the N-doped carbon sheet. Notably, these findings show the spin polarization of the asymmetric structure by introducing a strain effect on the C-C bonds for boosting ORR.

Metformin inhibits ovarian granular cell pyroptosis through the miR-670-3p/NOX2/ROS pathway.

Recent studies have demonstrated that ovarian granular cells (OGCs) pyroptosis is present in the ovaries of polycystic ovary syndrome (PCOS) mice and that NLRP3 activation destroys follicular functions. Metformin has been shown to protect against PCOS by reducing insulin resistance in women, whereas its role in OGC pyroptosis is unknown. This study aimed to investigate the impact of metformin on OGC pyroptosis and the underlying mechanisms. The results showed that treating a human granulosa-like tumor cell line (KGN) with metformin significantly decreased LPS-induced expression of miR-670-3p, NOX2, NLRP3, ASC, cleaved caspase-1, and GSDMD-N. Cellular caspase-1 activity; ROS production; oxidative stress; and the secretion of IL-1ß, IL-6, IL-18, and TNF-α were also diminished. These effects were amplified by adding N-acetyl-L-cysteine (NAC), a pharmacological inhibitor of ROS. In contrast, metformin's anti-pyroptosis and anti-inflammatory effects were robustly ameliorated by NOX2 overexpression in KGN cells. Moreover, bioinformatic analyses, RT-PCR, and Western blotting showed that miR-670-3p could directly bind to the NOX2 (encoded by the CYBB gene in humans) 3'UTR and decrease NOX2 expression. Metformin-induced suppression of NOX2 expression, ROS production, oxidative stress, and pyroptosis was significantly alleviated by transfection with the miR-670-3p inhibitor. These findings suggest that metformin inhibits KGN cell pyroptosis via the miR-670-3p/NOX2/ROS pathway.

Highly Stable Pt-Based Oxygen Reduction Electrocatalysts toward Practical Fuel Cells: Progress and Perspectives.

The high cost and poor reliability of cathodic electrocatalysts for the oxygen reduction reaction (ORR), which requires significant amounts of expensive and scarce platinum, obstructs the broad applications of proton exchange membrane fuel cells (PEMFCs). The principles of ORR and the reasons for the poor stability of Pt-based catalysts are reviewed. Moreover, this paper discusses and categorizes the strategies for enhancing the stability of Pt-based catalysts in fuel cells. More importantly, it highlights the recent progress of Pt-based stability toward ORR, including surface-doping, intermetallic structures, 1D/2D structures, rational design of support, etc. Finally, for atomic-level in-depth information on ORR catalysts in fuel cells, potential perspectives are suggested, such as large-scale preparation, advanced interpretation techniques, and advanced simulation. This review aims to provide valuable insights into the fundamental science and technical engineering for practical Pt-based ORR electrocatalysts in fuel cells.

Full Endoscopy Combined with Allogeneic Bone Grafting for Benign Spinal Lesions: Technical Notes and Preliminary Clinical Results.

Benign lesions of the spine include benign tumors and tumor-like lesions of the spine, which usually occur in the thoracic and lumbar vertebrae. The incidence rate is low, accounting for about 1% of primary bone tumors. Few cases of endoscopic treatment of benign spinal lesions have been reported in the literature. Here, we introduce a new surgical technique using full endoscopy and allogeneic bone grafting to treat benign spinal lesions. All patients in this study successfully underwent the operation, and their pain was significantly relieved postoperatively. The patient VAS scores decreased from 3.07 ± 0.70 preoperatively to 0.33 ± 0.49 at the last follow-up visit (p < 0.05). The mean total blood loss (including drainage blood) was 16.67 ± 6.98 mL. The mean operative time was 63.33 ± 7.23 min. No patients developed numbness in the corresponding segmental distribution after surgery, none of the patients had serious postoperative complications, and none had focal recurrence during follow-up requiring reoperation. Patients reported symptom relief throughout the whole follow-up period. We believe that endoscopic surgery preserves the ligaments and soft tissues around the vertebral body, and that this technique is feasible with minimal trauma, rapid recovery, and good outcomes at short-term follow-up. This minimally invasive treatment modality offers a new option for the treatment of patients with benign spinal lesions.

Evolution of Stabilized 1T-MoS2 by Atomic-Interface Engineering of 2H-MoS2 /Fe-Nx towards Enhanced Sodium Ion Storage.

Metallic conductive 1T phase molybdenum sulfide (MoS2 ) has been identified as promising anode for sodium ion (Na+ ) batteries, but its metastable feature makes it difficult to obtain and its restacking during the charge/discharge processing result in part capacity reversibility. Herein, a synergetic effect of atomic-interface engineering is employed for constructing 2H-MoS2 layers assembled on single atomically dispersed Fe-N-C (SA Fe-N-C) anode material that boosts its reversible capacity. The work-function-driven-electron transfer occurs from SA Fe-N-C to 2H-MoS2 via the Fe-S bonds, which enhances the adsorption of Na+ by 2H-MoS2 , and lays the foundation for the sodiation process. A phase transfer from 2H to 1T/2H MoS2 with the ferromagnetic spin-polarization of SA Fe-N-C occurs during the sodiation/desodiation process, which significantly enhances the Na+ storage kinetics, and thus the 1T/2H MoS2 /SA Fe-N-C display a high electronic conductivity and a fast Na+ diffusion rate.

Altering Ligand Microenvironment of Atomically Dispersed CrN4 by Axial Ligand Sulfur for Enhanced Oxygen Reduction Reaction in Alkaline and Acidic Medium.

Because of the instability and Fenton reactivity of non-precious metal nitrogen-carbon based catalyst when processing the oxygen reduction reaction (ORR), seeking for electrocatalysts with highly efficient performance becomes very highly desired to speed up the commercialization of fuel cell. Herein, chromium (Cr)-N4  electrocatalyst containing extraterrestrial S formed axial S1 -Cr1 N4  bonds (S1 Cr1 N4 C) is achieved via an assembly polymerization and confined pyrolysis strategy. Benefiting from the adjusting  coordination configuration and electronic structure of the metal center through axial coordination, S1 Cr1 N4 C exhibits enhanced the intrinsic activity (half-wave potential (E1/2 ) is 0.90 V versus reversable hydrogen electrode, RHE) compared with that of CrN4 C and Pt/C catalysts. More notably, the catalyst is almost inert in catalyzing the Fenton reaction, and thus shows the high stability. Density functional theory (DFT) results further reveal that the existence of axial S atoms in S1 Cr1 N4 C moiety has the better ORR activity than Cr1 N4 C moieties. The axial S ligand in S1 Cr1 N4 C moiety can break the electron localization around the planar Cr1 N4  active center, which facilitated the rate-limiting reductive release of OH* and accelerated overall ORR process. The present work opens up a new avenue to modulate the axial ligand type of the single-atoms (SAs) active center to enhance intrinsic SAs performances.

Deep learning-based prediction of mandibular growth trend in children with anterior crossbite using cephalometric radiographs.

BACKGROUND: It is difficult for orthodontists to accurately predict the growth trend of the mandible in children with anterior crossbite. This study aims to develop a deep learning model to automatically predict the mandibular growth result into normal or overdeveloped using cephalometric radiographs. METHODS: A deep convolutional neural network (CNN) model was constructed based on the algorithm ResNet50 and trained on the basis of 256 cephalometric radiographs. The prediction behavior of the model was tested on 40 cephalograms and visualized by equipped with Grad-CAM. The prediction performance of the CNN model was compared with that of three junior orthodontists. RESULTS: The deep-learning model showed a good prediction accuracy about 85%, much higher when compared with the 54.2% of the junior orthodontists. The sensitivity and specificity of the model was 0.95 and 0.75 respectively, higher than that of the junior orthodontists (0.62 and 0.47 respectively). The area under the curve value of the deep-learning model was 0.9775. Visual inspection showed that the model mainly focused on the characteristics of special regions including chin, lower edge of the mandible, incisor teeth, airway and condyle to conduct the prediction. CONCLUSIONS: The deep-learning CNN model could predict the growth trend of the mandible in anterior crossbite children with relatively high accuracy using cephalometric images. The deep learning model made the prediction decision mainly by identifying the characteristics of the regions of chin, lower edge of the mandible, incisor teeth area, airway and condyle in cephalometric images.

METTL3-Mediated N6-Methyladenosine Modification of lncRNA D26496 Suppresses the Proliferation and Migration of Schwann Cells after Sciatic Nerve Injury.

Previous reports showed that LncRNA D26496 was downregulated and N6-methyladenosine (m6A) methyltransferase METTL3 was upregulated in sciatic nerve injury (SNI). YTH-Domain Family Member 2 (YTHDF2) regulated RNA degradation through recognizing m6A sites. However, whether METTL3-mediated m6A of D26496 plays a role in development of SNI is unknown. Therefore, in this study, we established a rat SNI model and a H2O2-induced Schwann cell injury model to investigate the role of D26496 in modulating SNI and how the expression of D26496 was regulated during this process. D26496 expression was downregulated in both models. Rats with SNI displayed severe oxidative stress, manifested as increased MDA production and decreased SOD and GSH activity. Moreover, overexpression of D26496 alleviated H2O2-induced Schwann cell injury likely by promoting cell proliferation and migration and suppressing cell apoptosis and oxidative stress. Mechanism studies found that METTL3 expression was upregulated after SNI, and silencing METTL3 reduced the D26496 m6A level, but upregulated D26496 expression. Subsequent studies found that YTHDF2 was upregulated after SNI, and abundant m6A modified D26496 in the precipitated protein-RNA complexes by anti-YTHDF2 antibody, whereas silencing YTHDF2 promoted D26496 expression but had no effect on m6A levels of D29496. Silencing D26496 reversed the protective effect of knocking down METTL3 or knocking down YTHDF2 on H2O2-induced cell damage. In vivo, D26496 overexpression alleviated SNI-induced neuropathic pain and oxidative stress. In conclusion, our results suggested that D26496 m6A modification mediated by METTL3 and recognition of D26496 m6A sites by YTHDF2 induced D26496 degradation, thereby participating in the progression of SNI.

Transcriptome-based molecular subtypes and differentiation hierarchies improve the classification framework of acute myeloid leukemia.

The current classification of acute myeloid leukemia (AML) relies largely on genomic alterations. Robust identification of clinically and biologically relevant molecular subtypes from nongenomic high-throughput sequencing data remains challenging. We established the largest multicenter AML cohort (n = 655) in China, with all patients subjected to RNA sequencing (RNA-Seq) and 619 (94.5%) to targeted or whole-exome sequencing (TES/WES). Based on an enhanced consensus clustering, eight stable gene expression subgroups (G1-G8) with unique clinical and biological significance were identified, including two unreported (G5 and G8) and three redefined ones (G4, G6, and G7). Apart from four well-known low-risk subgroups including PML::RARA (G1), CBFB::MYH11 (G2), RUNX1::RUNX1T1 (G3), biallelic CEBPA mutations or -like (G4), four meta-subgroups with poor outcomes were recognized. The G5 (myelodysplasia-related/-like) subgroup enriched clinical, cytogenetic and genetic features mimicking secondary AML, and hotspot mutations of IKZF1 (p.N159S) (n = 7). In contrast, most NPM1 mutations and KMT2A and NUP98 fusions clustered into G6-G8, showing high expression of HOXA/B genes and diverse differentiation stages, from hematopoietic stem/progenitor cell down to monocyte, namely HOX-primitive (G7), HOX-mixed (G8), and HOX-committed (G6). Through constructing prediction models, the eight gene expression subgroups could be reproduced in the Cancer Genome Atlas (TCGA) and Beat AML cohorts. Each subgroup was associated with distinct prognosis and drug sensitivities, supporting the clinical applicability of this transcriptome-based classification of AML. These molecular subgroups illuminate the complex molecular network of AML, which may promote systematic studies of disease pathogenesis and foster the screening of targeted agents based on omics.

Identification of Gαi3 as a novel molecular therapeutic target of cervical cancer.

Here we studied expression and potential functions of Gαi3 in cervical cancer. The bioinformatics analysis together with the results from local patients' tissues revealed that Gαi3 expression was remarkably elevated in human cervical cancer tissues and different cervical cancer cells, and was associated with poor overall survival and poor disease-specific survival of patients. Gαi3 depletion resulted in profound anti-cervical cancer activity. In primary or immortalized cervical cancer cells, Gαi3 shRNA or CRISPR/Cas9-caused Gαi3 knockout/KO largely hindered cell proliferation and migration, and provoked apoptosis. On the contrast, ectopic Gαi3 overexpression further enhanced cervical cancer proliferation and migration. Akt-mTOR activation in primary cervical cancer cells was significantly reduced after Gαi3 silencing or KO, but was augmented following Gαi3 overexpression. Further studies revealed that the transcription factor GATA4 binding to Gαi3 promoter region was significantly enhanced in cervical cancer tissues and cells. Gαi3 expression was decreased by GATA4 shRNA, but upregulated following GATA4 overexpression. In vivo, the growth of cervical cancer xenografts was robustly suppressed after Gαi3 silencing or KO. Gαi3 depletion and Akt-mTOR inactivation were detected in Gαi3-silenced/-KO cervical cancer xenograft tissues. Together, upregulated Gαi3 is a valuable oncotarget of cervical cancer.

Optimizing Atomically Dispersed Metal Electrocatalysts for Hydrogen Evolution: Chemical Coordination Effect and Electronic Metal Support Interaction.

Hydrogen has emerged as a green and sustainable fuel to meet the demand for future global energy. Distinct from steam reforming, electrochemical water splitting, especially powered by renewables, has been considered as a promising technique for scalable production of high-purity hydrogen with no carbon emission. Its commercialization depends on accelerating reaction kinetics and thus reduction of hydrogen cost, requiring electrocatalysts that are efficient, economical, and capable of stable and sustained hydrogen production. Atomically dispersed metal carbon-based catalysts (ADMCs) have attracted extensive attention due to their high atom utilization, abundant accessible active sites, fast mass transfer, and well-defined and tunable structures as ideal models for commercialized hydrogen production catalysts. However, boosting the performances of ADMCs for HER still requires new-captions of rational structural design. In this review, starting from the recently developed strategies of ADMCs synthesis, the microenvironment regulation of active sites of ADMCs are systematically summarized and discussed, such as atomically metal doping, synergetic atomically doping and ADMCs supported nanocrystals. With attention on the catalytic mechanisms and structure-activity relationships ranging from chemical coordination effects and electronic metal-support interaction, the active origin of ADMCs in the electrocatalytic hydrogen evolution reaction is discussed. Finally, the review outlooks the remaining challenges and emerging research topics in the future, including long service life, amplification preparation techniques, high-output alkaline water electrolysis, seawater electrolysis for hydrogen production and large current density hydrogen evolution. The new insights and knowledge into these aspects will be helpful for filling the existing gaps between scientific communities and industries and open up opportunities for bringing this promising technology into reality.

Phenotypic Spectrum and Molecular Basis in a Chinese Cohort of Osteogenesis Imperfecta With Mutations in Type I Collagen.

Osteogenesis imperfecta (OI) is a rare inherited connective tissue dysplasia characterized with skeletal fragility, recurrent fractures and bone deformity, predominantly caused by mutations in the genes COL1A1 or COL1A2 that encode the chains of type I collagen. In the present study, clinical manifestations and genetic variants were analysed from 187 Chinese OI patients, majority of whom are of southern Chinese origin. By targeted sequencing, 63 and 58 OI patients were found carrying mutations in COL1A1 and COL1A2 respectively, including 8 novel COL1A1 and 7 novel COL1A2 variants. We validated a novel splicing mutation in COL1A1. A diverse mutational and phenotypic spectrum was observed, coupling with the heterogeneity observed in the transcriptomic data derived from osteoblasts of six patients from our cohort. Missense mutations were significantly associated (χ2 p = 0.0096) with a cluster of patients with more severe clinical phenotypes. Additionally, the severity of OI was more correlated with the quality of bones, rather than the bone mineral density. Bone density is most responsive to bisphosphonate treatment during the juvenile stage (10-15 years old). In contrast, height is not responsive to bisphosphonate treatment. Our findings expand the mutational spectrum of type I collagen genes and the genotype-phenotype correlation in Chinese OI patients. The observation of effective bisphosphonate treatment in an age-specific manner may help to improve OI patient management.

Concave Pt-Zn Nanocubes with High-Index Faceted Pt Skin as Highly Efficient Oxygen Reduction Catalyst.

High dosage of expensive Pt to catalyze the sluggish oxygen reduction reaction (ORR) on the cathode severely impedes the commercialization of proton exchange membrane fuel cells. Therefore, it is urgent to cut down the Pt catalyst by efficiently improving the ORR activity while maintaining high durability. Herein, magic concave Pt-Zn nanocubes with high-index faceted Pt skin (Pt78 Zn22 ) are proposed for high-efficiency catalysis toward proton exchange membrane fuel cells. These unique structural features endow the Pt-skin Pt78 Zn22 /KB with a mass activity of 1.18 mA µgPt -1 and a specific activity of 3.64 mA cm-2 for the ORR at 0.9 V (vs RHE). Meanwhile, the H2 -O2 fuel cell assembled by this catalyst delivers an ultrahigh peak power density of ≈1449 mW cm-2 . Both experiments and theoretical calculations show that the electronic structure of the surface is adjusted, thereby shortening the length of the Pt-Pt bond and reducing the adsorption energy of OH*/O* on the Pt surface. This work demonstrates the synergistic effect of the oxidation-resistant metal Zn and the construction of Pt-rich surface engineering. Also, it guides the future development of catalysts for their practical applications in energy conversion technologies and beyond.

[A case-control study of minimally invasive transforaminal interbody fusion with the assistance of robot and traditional fluoroscopy in the treatment of single-space lumbar disc herniation].

OBJECTIVE: To compare the safety and nail placement accuracy of fluoroscopy-assisted and robot-assisted minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in the treatment of single-space lumbar disc herniation. METHODS: The clinical data of 52 patients with single-space lumbar disc herniation treated by MIS-TLIF from March 2019 to February 2020 were retrospectively analyzed. Among them, 24 patients were treated by robot-assisted MIS-TLIF(group A) and 28 patients were treated by fluoroscopy-assisted MIS-TLIF (group B). The intraoperative blood loss, operation time, intraoperative fluoroscopy times, preoperative and postoperative visual analogue scale(VAS), Japanese Orthopaedic Association(JOA) scores and operation-related complications were recorded in two groups. Gertzbein-Robbins grade according to CT scan was used to evaluate the nail placement after operation. Grade A and B were evaluated as satisfactory nail placement, and grade C, D, and E were evaluated as error placement. Babu's method was used to evaluate the screw's invasion to the superior articular process. RESULTS: The operation time, intraoperative blood loss and intraoperative fluoroscopy times in group A were less than those in group B(P<0.05).VAS and JOA scores of all patients at the final follow-up were significantly improved compared with those before operation(P<0.05), but there was no statistically significant difference between the groups(P>0.05). There were 96 and 112 screws in group A and group B, respectively. Three days after operation, according to the Gertzbein-Robbins grade to evaluate the nail placement accuracy, there were 90 screws of grade A, 5 of grade B, 1 of grade C, no grade D and E in group A;there were 84 screws of grade A, 16 of grade B, 8 of grade C, 4 of grade D, no grade E in group B;the difference between two groups was statistically significant(Z=-3.709, P=0.000). The satisfactory rate of screw placement in group A was 98.96% (95/96), and that of group B was 89.29% (100/112), the difference between two groups was statistically significant (χ2=8.254, P=0.004). Three days after operation, the invasion of superior facet joints by pedicle screws was evaluated according to Babu's method, including 90 screws in grade 0, 4 in grade 1, 2 in grade 2, and 0 in grade 3 in group A;86 in grade 0, 12 in grade 1, 10 in grade 2 and 4 in grade 3 in group B, and the difference was statistically significant(Z=-3.433, P=0.001). There were no serious spinal cord, nerve and vascular injuries and other operation-related complications caused by screw implantation failure in both groups. All patients were followed up from 6 to 12(9.06±1.60) months. The neurological symptoms improved well after operation. During the follow-up period, there was no recurrence of symptoms, loosening or breakage of the internal fixation. CONCLUSION: Compared with the traditional fluoroscopy-assisted MIS-TLIF, the spinal robot-assisted MIS-TLIF not only has more minimally invasive and safer, but also has higher accuracy in nail placement, lower incidence of upper articular process invasion, and more accurate decompression targets, which can be used for minimally invasive treatment of single-space lumbar disc herniation.