Human population history at the crossroads of East and Southeast Asia since 11,000 years ago.

Past human genetic diversity and migration between southern China and Southeast Asia have not been well characterized, in part due to poor preservation of ancient DNA in hot and humid regions. We sequenced 31 ancient genomes from southern China (Guangxi and Fujian), including two ∼12,000- to 10,000-year-old individuals representing the oldest humans sequenced from southern China. We discovered a deeply diverged East Asian ancestry in the Guangxi region that persisted until at least 6,000 years ago. We found that ∼9,000- to 6,000-year-old Guangxi populations were a mixture of local ancestry, southern ancestry previously sampled in Fujian, and deep Asian ancestry related to Southeast Asian Hòabìnhian hunter-gatherers, showing broad admixture in the region predating the appearance of farming. Historical Guangxi populations dating to ∼1,500 to 500 years ago are closely related to Tai-Kadai and Hmong-Mien speakers. Our results show heavy interactions among three distinct ancestries at the crossroads of East and Southeast Asia.

SMYD4 monomethylates PRMT5 and forms a positive feedback loop to promote hepatocellular carcinoma progression.

Both lysine and arginine methyltransferases are thought to be promising therapeutic targets for malignant tumors, yet how these methyltransferases function in malignant tumors, especially hepatocellular carcinoma (HCC), has not been fully elucidated. Here, we reported that SMYD4, a lysine methyltransferase, acts as an oncogene in HCC. SMYD4 was highly upregulated in HCC and promoted HCC cell proliferation and metastasis. Mechanistically, PRMT5, a well-known arginine methyltransferase, was identified as a SMYD4-binding protein. SMYD4 monomethylated PRMT5 and enhanced the interaction between PRMT5 and MEP50, thereby promoting the symmetrical dimethylation of H3R2 and H4R3 on the PRMT5 target gene promoter and subsequently activating DVL3 expression and inhibiting expression of E-cadherin, RBL2, and miR-29b-1-5p. Moreover, miR-29b-1-5p was found to inversely regulate SMYD4 expression in HCC cells, thus forming a positive feedback loop. Furthermore, we found that the oncogenic effect of SMYD4 could be effectively suppressed by PRMT5 inhibitor in vitro and in vivo. Clinically, high coexpression of SMYD4 and PRMT5 was associated with poor prognosis of HCC patients. In summary, our study provides a model of crosstalk between lysine and arginine methyltransferases in HCC and highlights the SMYD4-PRMT5 axis as a potential therapeutic target for the treatment of HCC.

Deficiency of thrombospondin-2 alleviates intimal hyperplasia in mice by modulating vascular smooth muscle cell proliferation and migration.

Thrombospondin-2 (Tsp2), a glycoprotein in the extracellular matrix, plays a critical role in the maintenance of vascular homeostasis. However, its role in the pathogenesis of cardiovascular disorders such as intimal hyperplasia is not fully elucidated. This study, therefore, aims to explore the effect of Tsp2 on intimal hyperplasia and its associated underlying mechanisms. Intimal hyperplasia (IH) was established using a modified wire-mediated femoral artery injury model. Immunofluorescence and qPCR identified upregulated Tsp2 expression in the injured femoral artery compared with the uninjured femoral artery. Similarly, TSP2 expression was also increased in human samples from the atherosclerotic femoral artery and colocalized with vascular smooth muscle cells (VSMCs). Compared with the wild-type littermates, Tsp2 knockout mice displayed a mitigated IH in the injured femoral artery, as demonstrated by a decreased neointimal area and intimal/median ratio. Primary mouse VSMCs were cultured to explore the mechanism by which Tsp2 influenced IH in vitro. PDGF-stimulated VSMCs presented an elevated Tsp2 expression and enhanced migration and proliferation. However, Tsp2 knockdown by siRNA blocked the increased migration and proliferation of VSMCs. Further analysis identified an association between Notch3 and IH when the intracellular domain of Notch3 (Nicd3) was upregulated in PDGF-stimulated VSMCs and femoral arteries with IH in human tissues. Along with the overexpression and downregulation of Tsp2, the Nicd3 expression was also up and downregulated accordingly. Tsp2 was associated with IH and may serve as a therapeutic target for IH. Downregulation of Tsp2 could mitigate the progression of IH by modulating the proliferation and migration of VSMCs.

Causal relationship between basal metabolic rate and intervertebral disc degeneration: a Mendelian randomization study.

BACKGROUND: The role of basal metabolic rate (BMR) in intervertebral disc degeneration (IVDD) is still uncertain. To address this gap, we conducted a Mendelian randomization (MR) study to comprehensively explore the causal relationship between BMR and IVDD. METHODS: BMR data were obtained from a large genome-wide association study (GWAS) database, while IVDD data were derived from the FinnGen project. The causal relationship between IVDD and BMR was investigated using MR, with inverse-variance weighting (IVW) as the primary estimate. MR-Egger weighed median and weighed mode were employed for robustness. Sensitivity analyses, including the Cochran Q test, leave-one-out analysis, and MR-Egger intercept analysis, were conducted. Furthermore, the study also identified causal relationships between IVDD and factors associated with BMR (hyperthyroidism, type 2 diabetes, standing height, weight, and body mass index). Multivariable MR was applied to further assess the direct effect of BMR on IVDD. RESULTS: Genetic predisposition to BMR (after removing outliers OR: 1.49; 95% CI: 1.37-1.63; P = 5.073e-21) were associated with an increased risk of IVDD. Additionally, IVDD risk increased with greater height, weight, and BMI. No causal relationship was observed between hy/thy and T2D and intervertebral disc degeneration (IVDD) (P > 0.05). In multivariable MR, a significant causal association between BMR and IVDD persisted, even after adjusting for BMI, height, and weight. CONCLUSION: In this study, we successfully identified that a higher BMR is independently and causally linked to IVDD, indicating an increased risk of developing IVDD. These findings suggest that managing BMR could potentially mitigate the risk of IVDD.

Unsupervised machine learning cluster analysis to identification EVAR patients clinical phenotypes based on radiomics.

OBJECTIVE: This study used unsupervised machine learning (UML) cluster analysis to explore clinical phenotypes of endovascular aortic repair (EVAR) for abdominal aortic aneurysm (AAA) patients based on radiomics. METHOD: We retrospectively reviewed 1785 patients with infra-renal AAA who underwent elective EVAR procedures between January 2010 and December 2020. Pyradiomics was used to extract the radiomics features. Statistical analysis was applied to determine the radiomics features that related to severe adverse events (SAEs) after EVAR. The selected features were used for UML cluster analysis in training set and validation in test set. Comparison of basic characteristics and radiomics features of different clusters. The Kaplan-Meier analysis was conducted to generate the cumulative incidence of freedom from SAEs rate. RESULT: A total of 1180 patients were enrolled. During the follow-up, 353 patients experienced EVAR-related SAEs. In total, 1223 radiomics features were extracted from each patient, of which 23 radiomics features were finally preserved to identify different clinical phenotypes. 944 patients were allocated to the training set. Three clusters were identified in training set, in which patients had identical clinical characteristics and morphological features, while varied considerably of selected radiomics features. This encouraging performance was further approved in the test set. In addition, each cluster was well differentiated from other clusters and Kaplan-Meier analysis showed significant differences of freedom from SAEs rate between different clusters both in the training (p = .0216) and test sets (p = .0253). CONCLUSION: Based on radiomics, UML cluster analysis can identify clinical phenotypes in EVAR patients with distinct long-term outcomes.

Cathodic deposition of MOF films: mechanism and applications.

Metal-organic framework (MOF) thin films could be used for ion/molecular sieving, sensing, catalysis, and energy storage, but thus far no large-scale applications are known. One of the reasons is the lack of convenient and controllable fabrication methods. This work reviews the cathodic deposition of MOF films, which has advantages (e.g., simple operations, mild conditions, and controllable MOF film thickness/morphology) over other reported techniques. Accordingly, we discuss the mechanism of the cathodic deposition of MOF films which consists of the electrochemically triggered deprotonation of organic linkers and the formation of inorganic building blocks. Thereafter, the main applications of cathodically deposited MOF films are introduced with the aim of showing this technique's wide-ranging applications. Finally, we give the remaining issues and outlooks of the cathodic deposition of MOF films to drive its future development.

The Synergetic Reduction of the Condensation Degree of Dissolved Lignin (DL) during the Refining Process of Wheat Straw Biomass Based on the MA/O3 System.

Lignin, a natural pol2ymer with a complex structure that is difficult to separate, is prone to C-C bond condensation during the separation process. To reduce the condensation of lignin, here, a novel method is proposed for separating the components by using a combination of maleic acid (MA)/ozone (O3) to co-treat wheat straw. The removal of lignin, glucan, and xylan was 38.07 ± 0.2%, 31.44 ± 0.1%, and 71.98 ± 0.1%, respectively, under the conditions of ball-milling of wheat straw for 6 h, reaction temperature of 60 °C, and O3 holding time of 9 min. Lignin-rich solutions were collected to extract the dissolved lignin (DL) after washing the treated samples. The DL obtained under MA/O3 conditions had a carboxyl group (-COOH) content of 2.96 mmol/g. The carboxyl group of MA underwent esterification with the hydroxyl group (-OH) at the γ position of lignin and O3 reacted on the positions of the lignin side chain or the phenolic ring, resulting in a break in the side chain and the opening of the phenolic ring to introduce the carboxyl group. The 2D-HSQC-NMR results revealed that the phenolic ring-opening reaction of lignin in the presence of O3 was essentially free of ß-ß and ß-5 condensation bonds.

Cathodic Deposition-Assisted Synthesis of Thin Glass MOF Films for High-Performance Gas Separations.

Glass metal-organic framework (MOF) films can be fabricated from their crystalline counterparts through a melt-quenching process and are prospective candidates for gas separation because of the elimination of the grain boundaries in crystalline MOF films. However, current techniques are limited to producing glass MOF films with a thickness of tens of micrometers, which leads to ultralow gas permeances. Here, we report a novel cathodic deposition-assisted synthesis of glass ZIF-62 films with a thickness as low as ~1 µm. Electrochemical analyses and deposition experiments suggest that the cathodic deposition can lead to pure crystalline ZIF-62 films with a controllable thickness of ~2 µm to ~15 µm. Accordingly, glass ZIF-62 films with a thickness of ~1 µm to ~10 µm can be obtained after a thermal treatment. The fabricated defect-free glass ZIF-62 film measuring 2 µm in thickness shows a remarkable CO2/N2 and CO2/CH4 selectivity of 31.4 and 33.4, respectively, with a CO2 permeance which is over 30 times higher than the best-performing glass ZIF-62 films in literature.

Upregulated Cytoskeletal Proteins Promote Pathological Angiogenesis in Moyamoya Disease.

BACKGROUND: Moyamoya disease (MMD) is a rare progressive vascular disease that leads to intracranial internal carotid artery stenosis and eventual occlusion. However, its pathogenesis remains unclear. The purpose of this study is to explore the role of abnormally expressed proteins in the pathogenesis of MMD. METHODS: Data-independent acquisition mass spectrometry identifies the differentially expressed proteins in MMD serum by detecting the serum from 60 patients with MMD and 20 health controls. The differentially expressed proteins were validated using enzyme linked immunosorbent assays. Immunofluorescence for superficial temporal artery and middle cerebral artery specimens was used to explore the morphological changes of vascular wall in MMD. In vitro experiments were used to explore the changes and mechanisms of differentially expressed proteins on endothelial cells. RESULTS: Proteomic analysis showed that a total of 14 726 peptides and 1555 proteins were quantified by mass spectrometry data. FLNA (filamin A) and ZYX (zyxin) proteins were significantly higher in MMD serum compared with those in health controls (Log2FC >2.9 and >2.8, respectively). Immunofluorescence revealed an intimal hyperplasia in superficial temporal artery and middle cerebral artery specimens of MMD. FLNA and ZYX proteins increased the proportion of endothelial cells in S phase and promoted their proliferation, angiogenesis, and cytoskeleton enlargement. Mechanistic studies revealed that AKT (serine/threonine kinase)/GSK-3ß (glycogen synthase kinase 3ß)/ß-catenin signaling pathway plays a major role in these FLNA- and ZYX-induced changes in endothelial cells. CONCLUSIONS: This study provides proteomic data on a large sample size of MMD. The differential expression of FLNA and ZYX in patient with MMD and following in vitro experiments suggest that these upregulated proteins are related to the pathology of cerebrovascular intimal hyperplasia in MMD and are involved in MMD pathogenesis, with diagnostic and therapeutic ramifications.

Room Temperature Synthesis Mediated Porphyrinic NanoMOF Enables Benchmark Electrochemical Biosensing.

Leveraging size effects, nanoparticles of metal-organic frameworks, nanoMOFs, have recently gained traction, amplifying their scopes in electrochemical sensing. However, their synthesis, especially under eco-friendly ambient conditions remains an unmet challenge. Herein, an ambient and fast secondary building unit (SBU)-assisted synthesis (SAS) route to afford a prototypal porphyrinic MOF, Fe-MOF-525 is introduced. Albeit the benign room temperature conditions, Fe-MOF-525(SAS) nanocrystallites obtained are of ≈30 nm size, relatively smaller than the ones conventional solvothermal methods elicit. Integrating Fe-MOF-525(SAS) as a thin film on a conductive indium tin oxide (ITO) surface affords Fe-MOF-525(SAS)/ITO, an electrochemical biosensor. Synergistic confluence of modular MOF composition, analyte-specific redox metalloporphyrin sites, and crystal downsizing contribute to its benchmark voltammetric uric acid (UA) sensing. Showcasing a wide linear range of UA detection with high sensitivity and low detection limit, this SAS strategy coalesces ambient condition synthesis and nanoparticle size control, paving a green way to advanced sensors.

Arginine methylation of HSPA8 by PRMT9 inhibits ferroptosis to accelerate hepatitis B virus-associated hepatocellular carcinoma progression.

BACKGROUND: The hepatitis B virus X (HBx) protein is an established cause of hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC). Whether arginine methylation regulates ferroptosis involved in HBx-induced HCC progression has not been reported. This study aimed to explore whether HBx-regulated protein arginine methyltransferase 9 (PRMT9) mediates the involvement of ferroptosis in the development of HCC. METHODS AND RESULTS: HBx inhibited ferroptosis through promoting PRMT9 expression in HCC cells. PRMT9 suppressed ferroptosis to accelerate HCC progression in vivo. PRMT9 targeted HSPA8 and enhanced arginine methylation of HSPA8 at R76 and R100 to regulate ferroptosis in HCC. HSPA8 overexpression altered the transcriptome profile of HepG2 cells, in particular, ferroptosis and immune-related pathways were significantly enriched by differentially expressed genes, including CD44. HSPA8 overexpression up-regulated CD44 expression and knockdown of CD44 significantly reversed the inhibition of ferroptosis caused by PRMT9 overexpression. CONCLUSIONS: In conclusion, HBx/PRMT9/HSPA8/CD44 axis is a vital signal pathway regulating ferroptosis in HCC cells. This study provides new opportunities and targets for the treatment of HBV-induced HCC.

Increased co-expression of PD1 and TIM3 is associated with poor prognosis and immune microenvironment heterogeneity in gallbladder cancer.

BACKGROUND: The effectiveness of immune checkpoint inhibitors in treating gallbladder cancer (GBC) remains unsatisfactory. Recently, several new immune checkpoints have been identified. However, investigations exploring these immune checkpoints in GBC are limited. In this study, we aim to investigate the expression patterns and clinical implications of various immune checkpoints, and further characterize the spatial and quantitative heterogeneity of immune components in GBC. METHODS: We employed single and multiplex immunohistochemistry to evaluate the expression of five immune checkpoint markers and four immune cell markers in the primary tumor core, hepatic invasion margin, and liver metastasis. Subsequently, we analyzed their interrelationships and their prognostic significance. RESULTS: We observed a robust positive correlation between PD1/TIM3 expression in GBC (R = 0.614, P < 0.001). The co-expression of PD1/TIM3 exhibited a synergistic effect in predicting poor prognosis among postoperative GBC patients. Further analysis revealed that the prognostic significance of PD1/TIM3 was prominent in the subgroup with high infiltration of CD8 + T cells (P < 0.001). Multiplex immunohistochemistry reveals that PD1 + TIM3 + FOXP3 + cells constitute a significant proportion of FOXP3 + TILs in GBC tissue. Moreover, the co-high expression of PD1 and TIM3 is positively correlated with the accumulation of CD8 + TILs at the hepatic invasion margin. Lastly, our findings indicated reduced expression levels of immune checkpoints and diminished immune cell infiltration in liver metastases compared to primary tumors. CONCLUSIONS: Increased co-expression of PD1/TIM3 is associated with poor prognosis in GBC patients and is related to the heterogeneity of immune microenvironment between GBC primary tumor and its hepatic invasion margin or liver metastases, which may be a potential target for future immunotherapy of GBC.

Electrosynthesis of Metal-Organic Framework Films with Well-Defined Facets.

The deposition of metal-organic framework (MOF) films with defined exposed facets is important to enhance the performance of these films for, for example, catalysis or separations. In this work, MOF films with specific exposed facets are electrodeposited anodically on various substrates (e. g. on copper-sputtered Si wafers, copper meshes, copper foams, and polypropylene membranes). The influence of the deposition parameters, including the pH of the solution, current density, concentration of linker, and solvent, on the exposed facets of the deposited MOFs was investigated. The results suggest that precise control over the supersaturation during anodic deposition is a possible strategy for synthesizing MOF crystals with well-defined exposed facets. This approach provides a powerful toolbox for various applications requiring crystal facet control of MOF films.

Review on Cell Structure Regulation and Performances Improvement of Porous Poly(Lactic Acid).

Recent advances in the cell structure regulation and performances improvement of porous poly(lactic acid) materials (PPMs) are systematically reviewed in this feature article. First, the typical processing methods, including template method, non-solvent induced phase separation, freeze-drying, and supercritical CO2  foaming, of PPMs are introduced emphatically. Their various cell morphologies by different processing methods are summarized: finger-like, honeycomb-like, fiber-like, through cell, open cell, closed cell, ball-like, and flower-like. Meanwhile, the transformation among different cell morphologies as well as the changes in cell size and cell density, having impact on the performances, is described. Second, the influence of stereo-complex crystals on the cell structure of PPMs is emphatically reviewed. Furthermore, the relationships between cell structure and properties that includes mechanical properties, thermal stability, heat insulation, and hydrophobicity, are elaborated. Eventually, the issues of PPMs worthy of further study are discussed.

Predictive Value of Laboratory Indicators for Endoleak During Short-Term Follow-Up After EVAR.

BACKGROUND: The aim of this study was to explore the predictive value of endoleak in short-term follow-up after endovascular aortic repair (EVAR) of abdominal aortic aneurysm (AAA) via perioperative laboratory indicators. METHODS: A retrospective study included 200 consecutive patients who received standard EVAR treatment for AAA and were followed-up for 1 year. Binary logistic regression analysis was used to evaluate the correlation of the level and changes of perioperative laboratory indicators with the endoleak events during the follow-up. The receiver operating characteristic (ROC) curve was used to assess the predictive value of laboratory indicators for endoleak. RESULTS: A total of 45 cases of endoleak events occurred during follow-up. Binary logistic regression analysis showed that postoperative fibrinogen decrease, perioperative lymphocyte difference and lymphocyte monocyte ratio (LMR) difference were independent risk factors for short term endoleak. The area under the ROC curve (AUC) of postoperative fibrinogen was 0.596, the cut-off value was 284 mg/dl, and the corresponding specificity and sensitivity were 0.644 and 0.568. The AUC of the lymphocyte difference was 0.622, the cut-off value was -0.45 × 109/L, and the corresponding specificity and sensitivity were 0.651 and 0.568. The AUC of the LMR difference was 0.597, the cut-off value was -1.719, and the corresponding specificity and sensitivity were 0.631 and 0.614. CONCLUSIONS: Decrease of postoperative fibrinogen, increase of lymphocyte difference and LMR difference were independent predictive factors for endoleak in short-term follow-up after EVAR for AAA.

A radiomics model for predicting the outcome of endovascular abdominal aortic aneurysm repair based on machine learning.

OBJECTIVE: This study aimed to develop a radiomics model to predict the outcome of endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA), based on machine learning (ML) algorithms. METHODS: We retrospectively reviewed 711 patients with infra-renal AAA who underwent elective EVAR procedures between January 2016 and December 2019 at our single center. The radiomics features of AAA were extracted using Pyradiomics. Pearson correlation analysis, analysis of variance (ANOVA), least absolute shrinkage, and selection operator (LASSO) regression were applied to determine the predictors for EVAR-related severe adverse events (SAEs). Eighty percent of patients were classified as the training set and the remaining 20 percent of patients were classified as the test set. The selected features were used to build a radiomics model in training set using different ML algorithms. The performance of each model was assessed using the area under the curve (AUC) from the receiver operating characteristic (ROC) curve in the test set. RESULTS: A total of 493 patients were enrolled in this study, the mean follow-up time was 32 months. During the follow-up, 156 (31.6%) patients experienced EVAR-related SAEs. A total of 1223 radiomics features were extracted from each patient, of which 30 radiomics features were finally identified. The quantitative performance assessment and the ROC curves indicated that the logistics regression (LR) model had better predictive value than others, with accuracy, 0.86; AUC, 0.93; and F1 score, 0.91. The Rad-score waterfall plot showed that the overall amount of error was small both in the training set and in the test set. Calibration curve showed that the calibration degree of the training set and the test set were good (p > 0.05). Decision curve analysis (threshold 0.32) demonstrated that the model had good clinical applicability. CONCLUSION: Our radiomics model could be used as an efficient and adjunctive tool to predict the outcome after EVAR.

Endovascular treatment of type B aortic dissection in patients with end-stage renal disease.

OBJECTIVES: This study aimed to evaluate the postoperative and intermediate outcomes of thoracic endovascular aortic repair (TEVAR) in patients with end-stage renal disease (ESRD). METHODS: We retrospectively reviewed patients with type B aortic dissection (TBAD) undergoing TEVAR at our single center from January 2010 to December 2020. Patients with pre-existing ESRD were enrolled as the study group. One hundred consecutive patients from September 2013 to March 2015 without ESRD were included as the control group. The primary and secondary outcomes were adverse events and survival, respectively. Kaplan-Meier curves of survival and freedom from adverse events were calculated and analyzed using the log-rank univariate test. Multivariable analysis was used to isolate the effects of ESRD. RESULTS: A total of 39 patients with ESRD and TBAD underwent TEVAR during the study period. The median follow-up time of patients with and without ESRD was 45 and 46 months, respectively. There was significant difference between the survival at 4 years of patients with and without ESRD (72.8% vs 94.9%; p = 0.011). Meanwhile, the incidence of adverse events was significantly higher in patients with ESRD (p = 0.026). Multivariable logistic regression analysis showed that ESRD (OR, 2.46; p = 0.049) and peripheral artery disease (OR, 4.11; p = 0.002) were the predictors of adverse events. CONCLUSIONS: The rates of adverse events and survival expectancy were poor in patients with ESRD and TBAD.

Hordenine improves Parkinsonian-like motor deficits in mice and nematodes by activating dopamine D2 receptor-mediated signaling.

Parkinson's disease (PD) is a chronic neurodegenerative disease characterized by selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the striatum, leading to dopamine (DA) deficiency in the striatum and typical motor symptoms. A small molecule as a dietary supplement for PD would be ideal for practical reasons. Hordenine (HOR) is a phenolic phytochemical marketed as a dietary supplement found in cereals and germinated barley, as well as in beer, a widely consumed beverage. This study was aimed to identify HOR as a dopamine D2 receptor (DRD2) agonist in living cells, and investigate the alleviative effect and mechanism of HOR on PD-like motor deficits in mice and nematodes. Our results firstly showed that HOR is an agonist of DRD2, but not DRD1, in living cells. Moreover, HOR could improve the locomotor dysfunction, gait, and postural imbalance in MPTP- or 6-OHDA-induced mice or Caenorhabditis elegans, and prevent α-synuclein accumulation via the DRD2 pathway in C. elegans. Our results suggested that HOR could activate DRD2 to attenuate the PD-like motor deficits, and provide scientific evidence for the safety and reliability of HOR as a dietary supplement.

Critical Role of Phosphorus in Hollow Structures Cobalt-Based Phosphides as Bifunctional Catalysts for Water Splitting.

Cobalt phosphides electrocatalysts have great potential for water splitting, but the unclear active sides hinder the further development of cobalt phosphides. Wherein, three different cobalt phosphides with the same hollow structure morphology (CoP-HS, CoP2 -HS, CoP3 -HS) based on the same sacrificial template of ZIF-67 are prepared. Surprisingly, these cobalt phosphides exhibit similar OER performances but quite different HER performances. The identical OER performance of these CoPx -HS in alkaline solution is attributed to the similar surface reconstruction to CoOOH. CoP-HS exhibits the best catalytic activity for HER among these CoPx -HS in both acidic and alkaline media, originating from the adjusted electronic density of phosphorus to affect absorption-desorption process on H. Moreover, the calculated ΔGH* based on P-sites of CoP-HS follows a quite similar trend with the normalized overpotential and Tafel slope, indicating the important role of P-sites for the HER process. Moreover, CoP-HS displays good performance (cell voltage of 1.67 V at a current density of 50 mA cm-2 ) and high stability in 1 M KOH. For the first time, this work detailly presents the critical role of phosphorus in cobalt-based phosphides for water splitting, which provides the guidance for future investigations on transition metal phosphides from material design to mechanism understanding.

Fibroblast growth factor 10 attenuates chronic obstructive pulmonary disease by protecting against glycocalyx impairment and endothelial apoptosis.

BACKGROUND: The defects and imbalance in lung repair and structural maintenance contribute to the pathogenesis of chronic obstructive pulmonary diseases (COPD), yet the molecular mechanisms that regulate lung repair process are so far incompletely understood. We hypothesized that cigarette smoking causes glycocalyx impairment and endothelial apoptosis in COPD, which could be repaired by the stimulation of fibroblast growth factor 10 (FGF10)/FGF receptor 1 (FGFR1) signaling. METHODS: We used immunostaining (immunohistochemical [IHC] and immunofluorescence [IF]) and enzyme-linked immunosorbent assay (ELISA) to detect the levels of glycocalyx components and endothelial apoptosis in animal models and in patients with COPD. We used the murine emphysema model and in vitro studies to determine the protective and reparative role of FGF10/FGFR1. RESULTS: Exposure to cigarette smoke caused endothelial glycocalyx impairment and emphysematous changes in murine models and human specimens. Pretreatment of FGF10 attenuated the development of emphysema and the shedding of glycocalyx components induced by CSE in vivo. However, FGF10 did not attenuate the emphysema induced by endothelial-specific killing peptide CGSPGWVRC-GG-D(KLAKLAK)2. Mechanistically, FGF10 alleviated smoke-induced endothelial apoptosis and glycocalyx repair through FGFR1/ERK/SOX9/HS6ST1 signaling in vitro. FGF10 was shown to repair pulmonary glycocalyx injury and endothelial apoptosis, and attenuate smoke-induced COPD through FGFR1 signaling. CONCLUSIONS: Our results suggest that FGF10 may serve as a potential therapeutic strategy against COPD via endothelial repair and glycocalyx reconstitution.