MolPhase, an advanced prediction algorithm for protein phase separation.

We introduce MolPhase, an advanced algorithm for predicting protein phase separation (PS) behavior that improves accuracy and reliability by utilizing diverse physicochemical features and extensive experimental datasets. MolPhase applies a user-friendly interface to compare distinct biophysical features side-by-side along protein sequences. By additional comparison with structural predictions, MolPhase enables efficient predictions of new phase-separating proteins and guides hypothesis generation and experimental design. Key contributing factors underlying MolPhase include electrostatic pi-interactions, disorder, and prion-like domains. As an example, MolPhase finds that phytobacterial type III effectors (T3Es) are highly prone to homotypic PS, which was experimentally validated in vitro biochemically and in vivo in plants, mimicking their injection and accumulation in the host during microbial infection. The physicochemical characteristics of T3Es dictate their patterns of association for multivalent interactions, influencing the material properties of phase-separating droplets based on the surrounding microenvironment in vivo or in vitro. Robust integration of MolPhase's effective prediction and experimental validation exhibit the potential to evaluate and explore how biomolecule PS functions in biological systems.

A highly bioactive THPC-crosslinked recombinant collagen hydrogel implant for aging skin rejuvenation.

Skin aging, a complex physiological progression marked by collagen degradation, poses substantial challenges in dermatology. Recombinant collagen emerges as a potential option for skin revitalization, yet its application is constrained by difficulties in forming hydrogels. We have for the first time developed a highly bioactive Tetrakis(hydroxymethyl) phosphonium chloride (THPC)-crosslinked recombinant collagen hydrogel implant for aging skin rejuvenation. THPC demonstrated superior crosslinking efficiency compared to traditional agents such as EDC/NHS and BDDE, achieving complete recombinant collagen crosslinking at minimal concentrations and effectively inducing hydrogel formation. THPC's four reactive hydroxymethyl groups facilitate robust crosslinking with triple helical recombinant collagen, producing hydrogels with enhanced mechanical strength, excellent injectability, increased stability, and greater durability. Moreover, the hydrogel exhibited remarkable biocompatibility and bioactivity, significantly promoting the proliferation, adhesion, and migration of human foreskin fibroblast-1. In photoaged mice skin models, the THPC-crosslinked collagen hydrogel implant notably improved dermal density, skin elasticity, and reduced transepidermal water loss, creating a conducive environment for fibroblast activity and healthy collagen regeneration. Additionally, it elevated superoxide dismutase (SOD) activity and displayed substantial anti-calcification properties. The THPC-crosslinked recombinant collagen hydrogel implant presents an innovative methodology in combating skin aging, offering significant promise in dermatology and tissue engineering.

Use of artificial intelligence in breast surgery: a narrative review.

Background and Objective: We have witnessed tremendous advances in artificial intelligence (AI) technologies. Breast surgery, a subspecialty of general surgery, has notably benefited from AI technologies. This review aims to evaluate how AI has been integrated into breast surgery practices, to assess its effectiveness in improving surgical outcomes and operational efficiency, and to identify potential areas for future research and application. Methods: Two authors independently conducted a comprehensive search of PubMed, Google Scholar, EMBASE, and Cochrane CENTRAL databases from January 1, 1950, to September 4, 2023, employing keywords pertinent to AI in conjunction with breast surgery or cancer. The search focused on English language publications, where relevance was determined through meticulous screening of titles, abstracts, and full-texts, followed by an additional review of references within these articles. The review covered a range of studies illustrating the applications of AI in breast surgery encompassing lesion diagnosis to postoperative follow-up. Publications focusing specifically on breast reconstruction were excluded. Key Content and Findings: AI models have preoperative, intraoperative, and postoperative applications in the field of breast surgery. Using breast imaging scans and patient data, AI models have been designed to predict the risk of breast cancer and determine the need for breast cancer surgery. In addition, using breast imaging scans and histopathological slides, models were used for detecting, classifying, segmenting, grading, and staging breast tumors. Preoperative applications included patient education and the display of expected aesthetic outcomes. Models were also designed to provide intraoperative assistance for precise tumor resection and margin status assessment. As well, AI was used to predict postoperative complications, survival, and cancer recurrence. Conclusions: Extra research is required to move AI models from the experimental stage to actual implementation in healthcare. With the rapid evolution of AI, further applications are expected in the coming years including direct performance of breast surgery. Breast surgeons should be updated with the advances in AI applications in breast surgery to provide the best care for their patients.

Nitrogen Doping-Roused Synergistic Active Sites in Perovskite Enabling Highly Selective CO2 Photoreduction into CH4.

The intricate protonation process in carbon dioxide reduction usually makes the product unpredictable. Thus, it is significant to control the reactive intermediates to manipulate the reaction steps. Here, we propose that the synergistic La-Ti active sites in the N-La2Ti2O7 nanosheets enable the highly selective carbon dioxide photoreduction into methane. In the photoreduction of CO2 over N-La2Ti2O7 nanosheets, in situ Fourier transform infrared spectra are utilized to monitor the *CH3O intermediate, pivotal for methane production, whereas such monitoring is not conducted for La2Ti2O7 nanosheets. Also, theoretical calculations testify to the increased charge densities on the Ti and La atoms and the regulated formation energy barrier of *CO and *CH3O intermediates by the constructed synergistic active sites. Accordingly, the methane formation rate of 7.97 µL h-1 exhibited by the N-La2Ti2O7 nanosheets, along with an electron selectivity of 96.6%, exceeds that of most previously reported catalysts under similar conditions.

Clinical manifestations, antimicrobial resistance and genomic feature analysis of multidrug-resistant Elizabethkingia strains.

BACKGROUND: Elizabethkingia is emerging as an opportunistic pathogen in humans. The aim of this study was to investigate the clinical epidemiology, antimicrobial susceptibility, virulence factors, and genome features of Elizabethkingia spp. METHODS: Clinical data from 71 patients who were diagnosed with Elizabethkingia-induced pneumonia and bacteremia between August 2019 and September 2021 were analyzed. Whole-genome sequencing was performed on seven isolates, and the results were compared with a dataset of 83 available Elizabethkingia genomes. Genomic features, Kyoto Encyclopedia of Genes and Genomes (KEGG) results and clusters of orthologous groups (COGs) were analyzed. RESULTS: The mean age of the patients was 56.9 ± 20.7 years, and the in-hospital mortality rate was 29.6% (21/71). Elizabethkingia strains were obtained mainly from intensive care units (36.6%, 26/71) and emergency departments (32.4%, 23/71). The majority of the strains were isolated from respiratory tract specimens (85.9%, 61/71). All patients had a history of broad-spectrum antimicrobial exposure. Hospitalization for invasive mechanical ventilation or catheter insertion was found to be a risk factor for infection. The isolates displayed a high rate of resistance to cephalosporins and carbapenems, but all were susceptible to minocycline and colistin. Genomic analysis identified five ß-lactamase genes (blaGOB, blaBlaB, blaCME, blaOXA, and blaTEM) responsible for ß-lactam resistance and virulence genes involved in stress adaptation (ureB/G, katA/B, and clpP), adherence (groEL, tufA, and htpB) and immune modulation (gmd, tviB, cps4J, wbtIL, cap8E/D/G, and rfbC). Functional analysis of the COGs revealed that "metabolism" constituted the largest category within the core genome, while "information storage and processing" was predominant in both the accessory and unique genomes. The unique genes in our 7 strains were mostly enriched in KEGG pathways related to microRNAs in cancer, drug resistance (ß-lactam and vancomycin), ABC transporters, biological metabolism and biosynthesis, and nucleotide excision repair mechanisms. CONCLUSION: The Elizabethkingia genus exhibits multidrug resistance and carries carbapenemase genes. This study presents a comparative genomic analysis of Elizabethkingia, providing knowledge that facilitates a better understanding of this microorganism.

Deterioration phenomenon of Pb-contaminated aqueous solution remediation and enhancement mechanism of nano-hydroxyapatite-assisted biomineralization.

Modern metallurgical and smelting activities discharge the lead-containing wastewater, causing serious threats to human health. Bacteria and urease applied to microbial-induced carbonate precipitation (MICP) and enzyme-induced carbonate precipitation (EICP) are denatured under high Pb2+ concentration. The nano-hydroxyapatite (nHAP)-assisted biomineralization technology was applied in this study for Pb immobilization. Results showed that the extracellular polymers and cell membranes failed to secure the urease activity when subjected to 60 mM Pb2+. The immobilization efficiency dropped to below 50% under MICP, whereas it due to a lack of extracellular polymers and cell membranes dropped to below 30% under EICP. nHAP prevented the attachment of Pb2+ either through competing with bacteria and urease or promoting Ca2+/Pb2+ ion exchange. Furthermore, CO32- from ureolysis replaced the hydroxyl (-OH) in hydroxylpyromorphite to encourage the formation of carbonate-bearing hydroxylpyromorphite of higher stability (Pb10(PO4)6CO3). Moreover, nHAP application overcame an inability to provide nucleation sites by urease. As a result, the immobilization efficiency, when subjected to 60 mM Pb2+, elevated to above 80% under MICP-nHAP and to some 70% under EICP-nHAP. The findings highlight the potential of applying the nHAP-assisted biomineralization technology to Pb-containing water bodies remediation.

Assessing the technical efficiency performance of Chinese ports logistics: Evidence from the DEA and fsQCA.

Ports are critical centers of international trade and global logistics now that economic globalization has taken hold. The efficiency performance of port logistics is crucial to building an emerging pattern of development in which domestic and foreign dual cycles are complementary for China. This paper examines the efficiency performance of 19 ports within five major economic circles in China. It explores how their efficiency is distributed, and the configurations of efficiency improvement during the new normal of China's economy. First, the DEA-BCC model is employed to calculate the technical efficiency performance and distribution of each port from 2011 to 2020. Then, fuzzy-set qualitative comparative analysis (fsQCA) was applied to integrate and analyze the influencing factors. The results show as follows: (1) Each port group performed differently on efficiency rankings, as well as regional distributions. Among these, the port groups of the Bohai Rim region, the Yangtze River Delta region, and the Bohai Rim region continue to rank highly. (2) From the perspective of configuration analysis, the results suggest that government support is not necessary for port logistics with better economic endowments. However, it is critical for backward ones. (3) A rational industrial structure can enhance levels of infrastructure, openness, and information technology, improving port performance. The findings can provide theoretical and practical references for better promoting the development of Chinese port management.al references for better promoting the development of Chinese port management.

CDK5RAP3 is a novel super-enhancer-driven gene activated by master TFs and regulates ER-Phagy in neuroblastoma.

Super enhancers (SEs) are genomic regions comprising multiple closely spaced enhancers, typically occupied by a high density of cell-type-specific master transcription factors (TFs) and frequently enriched in key oncogenes in various tumors, including neuroblastoma (NB), one of the most prevalent malignant solid tumors in children originating from the neural crest. Cyclin-dependent kinase 5 regulatory subunit-associated protein 3 (CDK5RAP3) is a newly identified super-enhancer-driven gene regulated by master TFs in NB; however, its function in NB remains unclear. Through an integrated study of publicly available datasets and microarrays, we observed a significantly elevated CDK5RAP3 expression level in NB, associated with poor patient prognosis. Further research demonstrated that CDK5RAP3 promotes the growth of NB cells, both in vitro and in vivo. Mechanistically, defective CDK5RAP3 interfered with the UFMylation system, thereby triggering endoplasmic reticulum (ER) phagy. Additionally, we provide evidence that CDK5RAP3 maintains the stability of MEIS2, a master TF in NB, and in turn, contributes to the high expression of CDK5RAP3. Overall, our findings shed light on the molecular mechanisms by which CDK5RAP3 promotes tumor progression and suggest that its inhibition may represent a novel therapeutic strategy for NB.

Comparative Analysis of Single-Cell RNA Sequencing Methods with and without Sample Multiplexing.

Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful technique for investigating biological heterogeneity at the single-cell level in human systems and model organisms. Recent advances in scRNA-seq have enabled the pooling of cells from multiple samples into single libraries, thereby increasing sample throughput while reducing technical batch effects, library preparation time, and the overall cost. However, a comparative analysis of scRNA-seq methods with and without sample multiplexing is lacking. In this study, we benchmarked methods from two representative platforms: Parse Biosciences (Parse; with sample multiplexing) and 10x Genomics (10x; without sample multiplexing). By using peripheral blood mononuclear cells (PBMCs) obtained from two healthy individuals, we demonstrate that demultiplexed scRNA-seq data obtained from Parse showed similar cell type frequencies compared to 10x data where samples were not multiplexed. Despite relatively lower cell capture affecting library preparation, Parse can detect rare cell types (e.g., plasmablasts and dendritic cells) which is likely due to its relatively higher sensitivity in gene detection. Moreover, a comparative analysis of transcript quantification between the two platforms revealed platform-specific distributions of gene length and GC content. These results offer guidance for researchers in designing high-throughput scRNA-seq studies.

Design, Synthesis, and Evaluation of [18F]BIBD-300 as a Positron Emission Tomography Tracer for Poly(ADP-Ribose) Polymerase-1.

Compounds 8a-j were designed to adjust the mode of interaction and lipophilicity of FTT by scaffold hopping and changing the length of the alkoxy groups. Compounds 8a, 8d, 8g, and BIBD-300 were screened for high-affinity PARP-1 through enzyme inhibition assays and are worthy of further evaluation. PET imaging of MCF-7 subcutaneous tumors with moderate expression of PARP-1 showed that compared to [18F]FTT, [18F]8a, [18F]8d, and [18F]8g exhibited greater nonspecific uptake, a lower target-to-nontarget ratio, and severe defluorination, while [18F]BIBD-300 exhibited lower nonspecific uptake and a greater target-to-nontarget ratio. PET imaging of 22Rv1 subcutaneous tumors, which highly express PARP-1, confirmed that the uptake of [18F]BIBD-300 in normal organs, such as the liver, muscle, and bone, was lower than that of [18F]FTT, and the ratio of tumor-to-muscle and tumor-to-liver [18F]BIBD-300 was greater than that of [18F]FTT. The biodistribution results in mice with MCF-7 and 22Rv1 subcutaneous tumors further validated the results of PET imaging. Unlike [18F]FTT, which mainly relies on hepatobiliary clearance, [18F]BIBD-300, which has lower lipophilicity, undergoes a partial shift from hepatobiliary to renal clearance, providing the possibility for [18F]BIBD-300 to indicate liver cancer. The difference in the PET imaging results for [18F]FTT, [18F]BIBD-300, and [18F]8j in 22Rv1 mice and the corresponding molecular docking results further confirmed that subtle structural modifications in lipophilicity greatly optimize the properties of the tracer. Cell uptake experiments also demonstrated that [18F]BIBD-300 has a high affinity for PARP-1. Metabolized and unmetabolized [18F]FTT and [18F]BIBD-300 were detected in the brain, indicating that they could not accurately quantify the amount of PARP-1 in the brain. However, PET imaging of glioma showed that both [18F]FTT and [18F]BIBD-300 could accurately localize both in situ to C6 and U87MG tumors. Based on its potential advantages in the diagnosis of breast cancer, prostate cancer, and glioma, as well as liver cancer, [18F]BIBD-300 is a new option for an excellent PARP-1 tracer.

Identification and health risk evaluation of soil contaminated by polycyclic aromatic hydrocarbons at shale gas extraction sites based on positive matrix factorization.

The impact of shale gas extraction on surrounding environmental media remains unclear. In this study, the current state of contamination by polycyclic aromatic hydrocarbons (PAHs), which are high-frequency contaminants of shale gas, was investigated in the soil surrounding emerging shale gas development sites. The source analysis of PAHs was conducted in the soils of shale gas extraction sites using positive matrix factorization (PMF). The health risk assessment (HRA) was calculated for ingestion, dermal contact, and inhalation exposures, and the priority sources of PAHs in the soil were jointly identified by PMF and HRA to refine the contribution level of different individual PAHs to the carcinogenic risk. The results showed that both Sichuan and Chongqing mining site soils were contaminated to different degrees. Shale gas extraction has an impact on the surrounding soil, and the highest contributing source of PAHs in the mining site soil of Sichuan was anthropogenic activity, accounting for 31.6%, whereas that in the mining site soil of Chongqing was biomass combustion and mixed automobile combustion, accounting for 35.9%. At the two mining sites in Sichuan and Chongqing, none of the three exposure pathways (ingestion, dermal contact, and inhalation) posed a carcinogenic risk to children, whereas the dermal exposure pathway posed a carcinogenic risk to adults. Health risk assessments based on specific source assignments indicate that when managing soil pollution, the control of fossil fuel combustion and vehicular emissions should be prioritized.

Free hemi-hamate arthroplasty: A review of donor site outcomes.

Introduction: The use of the dorsal hamate as a free osteochondral bone graft or vascularized bone flap has become the mainstay for large, comminuted middle phalanx volar lip fractures. To date, few studies have been conducted in the assessment of donor site morbidity for the hemi-hamate graft or flap, and none have discussed modes of repair or reconstruction of this donor site. Methods: A retrospective analysis of 14 hemi-hamate arthroplasty (HHA) procedures, including 6 vascularized and 8 non-vascularized grafts, from two surgeons was performed. Four hamate defect reconstruction techniques were utilized: no formal reconstruction, autologous bone grafting, gel foam, or synthetic bone substitute. The dorsal capsule was repaired with either extensor retinaculum grafting or by direct closure. Wrist range of motion, pain scores, and radiographic alignment were assessed. Results: At 6 months follow-up, all patients achieved full, pain-free wrist motion compared to the uninjured side, with visual analog scale pain scores of 0. Serial radiographs showed maintained carpal alignment without instability or subluxation. No differences based on the hamate defect reconstruction method or capsular repair technique was demonstrated. Conclusion: Safe return to pain free, unrestricted wrist function is achievable after HHA, regardless of hamate donor site management. Adequate dorsal capsular repair appears critical to prevent instability. Further study is needed to compare techniques, but choice may be guided by surgeon preference in the absence of clear evidence.

Evaluating Extended Curettage and Adjuvant Therapy Against Wide Resection and Reconstruction in the Management of Distal Radius Giant Cell Tumors: A Systematic Review and Meta-analysis.

BACKGROUND: The management of distal radius giant cell tumors (GCTs) remains challenging, and the optimal approach is still a matter of debate. This systematic review and meta-analysis aimed to compare the outcomes of extended curettage and wide resection, the mainstays of treatment. METHODS: Medline (via PubMed), Cochrane Library, Web of Science, Google Scholar, ClinicalTrials.gov, and Embase databases were searched for comparative studies that assessed extended curettage with adjuvant therapy and wide resection with reconstruction in patients with GCTs of the distal radius up to April 2023. Data were collected and analyzed on rates of local recurrence, metastasis, overall complications, and functional outcomes. The Newcastle-Ottawa scale was used to appraise the risk of bias within each study. RESULTS: Fifteen studies (n = 373 patients) were included and analyzed. Patients who underwent curettage were more likely to develop recurrence (risk ratio [RR] = 3.02 [95% confidence interval; CI, 1.87-4.89], P < .01), showed fewer complications (RR = 0.32 [95% CI, 0.21-0.49], P < .01), and showed greater improvement in Visual Analog Scale and lower Disabilities of the Arm, Shoulder, and Hand scores (P < .00001) than those who underwent wide resection. No significant difference was found regarding metastasis (RR = 1.03 [95% CI, 0.38-2.78], P = .95). CONCLUSIONS: Regarding the surgical approach to GCT of the distal radius, curettage with adjuvant therapy was associated with a higher likelihood of recurrence compared with wide resection with reconstruction. Nevertheless, the curettage approach resulted in significantly lower rates of operative complications, decreased pain scores, and better functional outcomes in comparison to the resection group.

Self-Assembling Triple-Helix Recombinant Collagen Hydrogel Enriched with Tyrosine.

The self-assembly of collagen within the human body creates a complex 3D fibrous network, providing structural integrity and mechanical strength to connective tissues. Recombinant collagen plays a pivotal role in the realm of biomimetic natural collagen. However, almost all of the reported recombinant collagens lack the capability of self-assembly, severely hindering their application in tissue engineering and regenerative medicine. Herein, we have for the first time constructed a series of self-assembling tyrosine-rich triple helix recombinant collagens, mimicking the structure and functionality of natural collagen. The recombinant collagen consists of a central triple-helical domain characterized by the (Gly-Xaa-Yaa)n sequence, along with N-terminal and C-terminal domains featuring the GYY sequence. The introduction of GYY has a negligible impact on the stability of the triple-helical structure of recombinant collagen while simultaneously promoting its self-assembly into fibers. In the presence of [Ru(bpy)3]Cl2 and APS as catalysts, tyrosine residues in the recombinant collagen undergo covalent cross-linking, resulting in a hydrogel with exceptional mechanical properties. The recombinant collagen hydrogel exhibits outstanding biocompatibility and bioactivity, significantly enhancing the proliferation, adhesion, migration, and differentiation of HFF-1 cells. This innovative self-assembled triple-helix recombinant collagen demonstrates significant potential in the fields of tissue engineering and medical materials.

Breaking the Activity-Selectivity Trade-off for CH4-to-C2H6 Photoconversion.

Photocatalytic conversion of methane (CH4) to ethane (C2H6) has attracted extensive attention from academia and industry. Typically, the traditional oxidative coupling of CH4 (OCM) reaches a high C2H6 productivity, yet the inevitable overoxidation limits the target product selectivity. Although the traditional nonoxidative coupling of CH4 (NOCM) can improve the product selectivity, it still encounters unsatisfied activity, arising from being thermodynamically unfavorable. To break the activity-selectivity trade-off, we propose a conceptually new mechanism of H2O2-triggered CH4 coupling, where the H2O2-derived ·OH radicals are rapidly consumed for activating CH4 into ·CH3 radicals exothermically, which bypasses the endothermic steps of the direct CH4 activation by photoholes and the interaction between ·CH3 and ·OH radicals, affirmed by in situ characterization techniques, femtosecond transient absorption spectroscopy, and density-functional theory calculation. By this pathway, the designed Au-WO3 nanosheets achieve unprecedented C2H6 productivity of 76.3 mol molAu-1 h-1 with 95.2% selectivity, and TON of 1542.7 (TOF = 77.1 h-1) in a self-designed flow reactor, outperforming previously reported photocatalysts regardless of OCM and NOCM pathways. Also, under outdoor natural sunlight irradiation, the Au-WO3 nanosheets exhibit similar activity and selectivity toward C2H6 production, showing the possibility for practical applications. Interestingly, this strategy can be applied to other various photocatalysts (Au-WO3, Au-TiO2, Au-CeO2, Pd-WO3, and Ag-WO3), showing a certain universality. It is expected that the proposed mechanism adds another layer to our understanding of CH4-to-C2H6 conversion.

Exploring the Unknown: Evaluating ChatGPT's Performance in Uncovering Novel Aspects of Plastic Surgery and Identifying Areas for Future Innovation.

BACKGROUND: Artificial intelligence (AI) has emerged as a powerful tool in various medical fields, including plastic surgery. This study aims to evaluate the performance of ChatGPT, an AI language model, in elucidating historical aspects of plastic surgery and identifying potential avenues for innovation. METHODS: A comprehensive analysis of ChatGPT's responses to a diverse range of plastic surgery-related inquiries was performed. The quality of the AI-generated responses was assessed based on their relevance, accuracy, and novelty. Additionally, the study examined the AI's ability to recognize gaps in existing knowledge and propose innovative solutions. ChatGPT's responses were analysed by specialist plastic surgeons with extensive research experience, and quantitatively analysed with a Likert scale. RESULTS: ChatGPT demonstrated a high degree of proficiency in addressing a wide array of plastic surgery-related topics. The AI-generated responses were found to be relevant and accurate in most cases. However, it demonstrated convergent thinking and failed to generate genuinely novel ideas to revolutionize plastic surgery. Instead, it suggested currently popular trends that demonstrate great potential for further advancements. Some of the references presented were also erroneous as they cannot be validated against the existing literature. CONCLUSION: Although ChatGPT requires major improvements, this study highlights its potential as an effective tool for uncovering novel aspects of plastic surgery and identifying areas for future innovation. By leveraging the capabilities of AI language models, plastic surgeons may drive advancements in the field. Further studies are needed to cautiously explore the integration of AI-driven insights into clinical practice and to evaluate their impact on patient outcomes. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Highly Crystalline Iridium-Nickel Nanocages with Subnanopores for Acidic Bifunctional Water Splitting Electrolysis.

Developing efficient bifunctional materials is highly desirable for overall proton membrane water splitting. However, the design of iridium materials with high overall acidic water splitting activity and durability, as well as an in-depth understanding of the catalytic mechanism, is challenging. Herein, we successfully developed subnanoporous Ir3Ni ultrathin nanocages with high crystallinity as bifunctional materials for acidic water splitting. The subnanoporous shell enables Ir3Ni NCs optimized exposure of active sites. Importantly, the nickel incorporation contributes to the favorable thermodynamics of the electrocatalysis of the OER after surface reconstruction and optimized hydrogen adsorption free energy in HER electrocatalysis, which induce enhanced intrinsic activity of the acidic oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). Together, the Ir3Ni nanocages achieve 3.72 A/mgIr(η=350 mV) and 4.47 A/mgIr(η=40 mV) OER and HER mass activity, which are 18.8 times and 3.3 times higher than that of commercial IrO2 and Pt, respectively. In addition, their highly crystalline identity ensures a robust nanostructure, enabling good catalytic durability during the oxygen evolution reaction after surface oxidation. This work provides a new revenue toward the structural design and insightful understanding of metal alloy catalytic mechanisms for the bifunctional acidic water splitting electrocatalysis.

Novel Angiogenesis Role of GLP-1(32-36) to Rescue Diabetic Ischemic Lower Limbs via GLP-1R-Dependent Glycolysis in Mice.

BACKGROUND: Restoring the capacity of endothelial progenitor cells (EPCs) to promote angiogenesis is the major therapeutic strategy of diabetic peripheral artery disease. The aim of this study was to investigate the effects of GLP-1 (glucagon-like peptide 1; 32-36)-an end product of GLP-1-on angiogenesis of EPCs and T1DM (type 1 diabetes) mice, as well as its interaction with the classical GLP-1R (GLP-1 receptor) pathway and its effect on mitochondrial metabolism. METHODS: In in vivo experiments, we conducted streptozocin-induced type 1 diabetic mice as a murine model of unilateral hind limb ischemia to examine the therapeutic potential of GLP-1(32-36) on angiogenesis. We also generated Glp1r-/- mice to detect whether GLP-1R is required for angiogenic function of GLP-1(32-36). In in vitro experiments, EPCs isolated from the mouse bone marrow and human umbilical cord blood samples were used to detect GLP-1(32-36)-mediated angiogenic capability under high glucose treatment. RESULTS: We demonstrated that GLP-1(32-36) did not affect insulin secretion but could significantly rescue angiogenic function and blood perfusion in ischemic limb of streptozocin-induced T1DM mice, a function similar to its parental GLP-1. We also found that GLP-1(32-36) promotes angiogenesis in EPCs exposed to high glucose. Specifically, GLP-1(32-36) has a causal role in improving fragile mitochondrial function and metabolism via the GLP-1R-mediated pathway. We further demonstrated that GLP-1(32-36) rescued diabetic ischemic lower limbs by activating the GLP-1R-dependent eNOS (endothelial NO synthase)/cGMP/PKG (protein kinase G) pathway. CONCLUSIONS: Our study provides a novel mechanism with which GLP-1(32-36) acts in modulating metabolic reprogramming toward glycolytic flux in partnership with GLP-1R for improved angiogenesis in high glucose-exposed EPCs and T1DM murine models. We propose that GLP-1(32-36) could be used as a monotherapy or add-on therapy with existing treatments for peripheral artery disease. REGISTRATION: URL: www.ebi.ac.uk/metabolights/; Unique identifier: MTBLS9543.