Genuine divalent magnesium-ion storage and fast diffusion kinetics in metal oxides at room temperature.

Rechargeable magnesium batteries represent a viable alternative to lithium-ion technology that can potentially overcome its safety, cost, and energy density limitations. Nevertheless, the development of a competitive room temperature magnesium battery has been hindered by the sluggish dissociation of electrolyte complexes and the low mobility of Mg2+ ions in solids, especially in metal oxides that are generally used in lithium-ion batteries. Herein, we introduce a generic proton-assisted method for the dissociation of the strong Mg-Cl bond to enable genuine Mg2+ intercalation into an oxide host lattice; meanwhile, the anisotropic Smoluchowski effect produced by titanium oxide lattices results in unusually fast Mg2+ diffusion kinetics along the atomic trough direction with a record high ion conductivity of 1.8 × 10-4 S ⋅ cm-1 on the same order as polymer electrolyte. The realization of genuine Mg2+ storage and fast diffusion kinetics enabled a rare high-power Mg-intercalation battery with inorganic oxides. The success of this work provides important information on engineering surface and interlayer chemistries of layered materials to tackle the sluggish intercalation kinetics of multivalent ions.

Orientational Water Bonding on Pt(111): Beyond the Frontier Orbital Principle.

For decades, our understanding of water-metal bonding has been dominated by the frontier orbital principle in which globally stable water-metal interactions are ruled by HOMO interacting with metal surfaces. Using density functional theory calculations, herein, we have revealed that the frontier orbital principle cannot be applied to metastable water bonding on Pt(111), where the decisive role of HOMO is replaced by HOMO-1 in terms of the greatest orbital shifts and depopulations as the two different bonding indicators. Unlike the stable water configuration in which both HOMO-1 and HOMO prefer to overlap with metal states through σ-like orbital interactions, metastable configurations exhibit delicate competition or balance between σ-like and π-like orbital interactions exerted by HOMO-1 and HOMO, respectively. These findings have significantly deepened our understanding of orbital roles in water-metal bonding interactions and bridged the gap between theoretical understanding of electrified waters at electrochemical interfaces and water science on metal surfaces.

Comparison of minimally invasive versus open pelvic organ-preserving radical cystectomy in female patients with bladder cancer: a multicenter propensity score matching analysis.

PURPOSE: To compare the perioperative and oncologic outcomes between minimally invasive pelvic organ-preserving radical cystectomy (MIPOPRC) and open pelvic organ-preserving radical cystectomy (open POPRC) among female patients with bladder cancer (BCa). METHODS: We identified female patients who underwent POPRC for BCa at three centers between January 2006 and April 2018. Female patients who underwent open POPRC were matched with those who underwent MIPOPRC using 1:1 propensity score (PS) matching. The patient demographics and perioperative and oncologic outcomes were evaluated for the comparison between MIPOPRC and open POPRC. RESULTS: Among the 158 patients enrolled, 83 patients underwent MIPOPRC, and 75 underwent open POPRC. A total of 60 MIPOPRC and 60 open POPRC patients were matched successfully. The cancer-specific survival (CSS) and recurrence-free survival (RFS) did not differ significantly in the propensity score-weighted cohort (p = 0.297 and p = 0.600, respectively). Subgroup analysis by age and pathologic stage in the matched cohort revealed that CSS and RFS were with no differences among all subgroups. Moreover, multivariable Cox regression analyses showed that the surgical approach (MIPOPRC vs open POPRC) was not a predictor of CSS (p = 0.250). CONCLUSION: MIPOPRC was non-inferior to open POPRC in terms of oncologic outcomes among female patients. MIPOPRC could be technically feasible in selected female patients with BCa.

Detecting Air Pollutant Molecules Using Tube-Shaped Single Electron Transistor.

An air pollution detector is proposed based on a tube-shaped single-electron transistor (SET) sensor. By monitoring the flow control component of the detector, each air pollutant molecule can be placed at the center of a SET nanopore and is treated as an island of the SET device in the same framework. Electron transport in the SET was incoherent, and the performances of the SET were sensitive at the single molecule level. Employing first-principles calculations, electronic features of an air pollutant molecule within a tube-shaped SET environment were found to be independent of the molecule rotational orientations with respect to axis of symmetry, unlike the electronic features in a conventional SET environment. Charge stability diagrams of the island molecules were demonstrated to be distinct for each molecule, and thus they can serve as electronic fingerprints for detection. Using the same setup, quantification of the air pollutant can be realized at room temperature as well. The results presented herein may help provide guidance for the identification and quantification of various types of air pollutants at the molecular level by treating the molecule as the island of the SET component in the proposed detector.

Elevated O-GlcNAcylation enhances pro-inflammatory Th17 function by altering the intracellular lipid microenvironment.

Chronic, low-grade inflammation increases the risk for atherosclerosis, cancer, and autoimmunity in diseases such as obesity and diabetes. Levels of CD4+ T helper 17 (Th17) cells, which secrete interleukin 17A (IL-17A), are increased in obesity and contribute to the inflammatory milieu; however, the relationship between signaling events triggered by excess nutrient levels and IL-17A-mediated inflammation is unclear. Here, using cytokine, quantitative real-time PCR, immunoprecipitation, and ChIP assays, along with lipidomics and MS-based approaches, we show that increased levels of the nutrient-responsive, post-translational protein modification, O-GlcNAc, are present in naive CD4+ T cells from a diet-induced obesity murine model and that elevated O-GlcNAc levels increase IL-17A production. We also found that increased binding of the Th17 master transcription factor RAR-related orphan receptor γ t variant (RORγt) at the IL-17 gene promoter and enhancer, as well as significant alterations in the intracellular lipid microenvironment, elevates the production of ligands capable of increasing RORγt transcriptional activity. Importantly, the rate-limiting enzyme of fatty acid biosynthesis, acetyl-CoA carboxylase 1 (ACC1), is O-GlcNAcylated and necessary for production of these RORγt-activating ligands. Our results suggest that increased O-GlcNAcylation of cellular proteins may be a potential link between excess nutrient levels and pathological inflammation.

Hepatocyte sortilin 1 knockout and treatment with a sortilin 1 inhibitor reduced plasma cholesterol in Western diet-fed mice.

Sortilin 1 (Sort1) is a member of the Vps10p domain intracellular trafficking receptor family. Genetic variations of the SORT1 gene are strongly associated with plasma cholesterol levels in humans. Recent studies have linked Sort1 to regulation of cholesterol metabolism in hepatocytes and pro-inflammatory response in macrophages, but the tissue-specific roles of Sort1 in lipid metabolism have not been well defined. We developed Sort1 floxed mice and investigated the development of Western diet (WD)-induced steatosis, hepatic inflammatory response, and hyperlipidemia in hepatocyte Sort1 KO mice and myeloid cell Sort1 KO mice. Our findings suggest that hepatocyte Sort1 deficiency attenuated diet-induced hepatic steatosis and hypercholesterolemia in mice. In contrast, myeloid Sort1 deficiency did not reduce hepatic cytokine expression or plasma cholesterol levels, but exacerbated hepatic triglyceride accumulation in WD-fed mice. Finally, we showed that treating WD-fed mice with an orally bioavailable Sort1 inhibitor, AF38469, decreased plasma cholesterol and hepatic cytokine expression. AF38469 treatment did not affect diet-induced obesity or insulin resistance, but was associated with reduced hepatic VLDL secretion and higher hepatic cholesterol 7α-hydrolase expression in WD-fed mice. In conclusion, findings from this study suggest that Sort1 loss-of-function in hepatocytes contributes to lower plasma cholesterol, and pharmacological inhibition of Sort1 attenuates diet-induced hypercholesterolemia in mice.

Molecular Bonding of Predissociative CO on Fe(100): Molecular Orbital Perspective.

On Fe(100), CO molecules can get activated efficiently so that CO bond breaking occurs with its transition state in close connection to the adsorbate. The CO bonding thus serves as a prototype model, nicely representing a balance of two simultaneous processes, namely, bond making with the surface and bond breaking within the adsorbate. Such unique configuration highlighting the interplay of two fundamental processes in one adsorption geometry, about which chemists have often fantasized, provides a viable solution to understand the very fundamental aspects of chemistry exemplified in a broad range of disciplines. Using density functional theory calculations, in this paper, we get a glimpse into how the CO bond activation is gestated and initiated in the adsorbate, wherein orbital cooperation in CO activation is evidenced by external CO bond making with the metal and internal CO bond breaking. We find that the symmetry breaking of occupied molecular orbitals in both 5σ and 1π symmetries marks efficient CO bond activation, which is reinforced by 1π → 2π excitations and 2π backdonation that are coupled with the symmetry transition of partially occupied 2π orbitals to a rotational symmetry. Our findings promote our knowledge of CO bond activation beyond the established picture of 5σ donation and 2π backdonation without symmetry breaking and may have insightful implications on orbital control of molecular activation, with further possible impact on elucidating the physical basis of heterogeneous catalysis.

Sortilin 1 Modulates Hepatic Cholesterol Lipotoxicity in Mice via Functional Interaction with Liver Carboxylesterase 1.

The liver plays a key role in cholesterol metabolism. Impaired hepatic cholesterol homeostasis causes intracellular free cholesterol accumulation and hepatocyte injury. Sortilin 1 (SORT1) is a lysosomal trafficking receptor that was identified by genome-wide association studies (GWAS) as a novel regulator of cholesterol metabolism in humans. Here we report that SORT1 deficiency protected against cholesterol accumulation-induced liver injury and inflammation in mice. Using an LC-MS/MS-based proteomics approach, we identified liver carboxylesterase 1 (CES1) as a novel SORT1-interacting protein. Mechanistic studies further showed that SORT1 may regulate CES1 lysosomal targeting and degradation and that SORT1 deficiency resulted in higher liver CES1 protein abundance. Previous studies have established an important role of hepatic CES1 in promoting intracellular cholesterol mobilization, cholesterol efflux, and bile acid synthesis. Consistently, high cholesterol atherogenic diet-challenged Sort1 knock-out mice showed less hepatic free cholesterol accumulation, increased bile acid synthesis, decreased biliary cholesterol secretion, and the absence of gallstone formation. SORT1 deficiency did not alter hepatic ceramide and fatty acid metabolism in high cholesterol atherogenic diet-fed mice. Finally, knockdown of liver CES1 in mice markedly increased the susceptibility to high cholesterol diet-induced liver injury and abolished the protective effect against cholesterol lipotoxicity in Sort1 knock-out mice. In summary, this study identified a novel SORT1-CES1 axis that regulates cholesterol-induced liver injury, which provides novel insights that improve our current understanding of the molecular links between SORT1 and cholesterol metabolism. This study further suggests that therapeutic inhibition of SORT1 may be beneficial in improving hepatic cholesterol homeostasis in metabolic and inflammatory liver diseases.

Inhibition of insulin/PI3K/AKT signaling decreases adipose Sortilin 1 in mice and 3T3-L1 adipocytes.

Sortilin 1(Sort1) is a vesicle trafficking receptor that mediates protein sorting in the endocytic and exocytic pathways. Sort1 is a component of the GLUT4 storage vesicles in adipocytes and is also involved in the regulation of adipogenesis. Sort1 protein is reduced in adipose of obese mice and humans, but the underlying cause is not fully understood. Here we report that insulin/PI3K/AKT signaling cascade critically regulates adipose Sort1 protein abundance. Administration of a PI3K inhibitor rapidly decreased Sort1 protein but not mRNA in adipose of chow-fed mice. In 3T3-L1 adipocytes, serum-starvation or inhibition of the PI3K/AKT signaling also decreased Sort1 protein without affecting Sort1 mRNA expression. Sort1 protein downregulation upon PI3K inhibition was blocked by pretreatment of MG132 but not Bafilomycin A1, suggesting that PI3K inhibition caused Sort1 degradation via the proteasome pathway. Using a phospho-specific Sort1 antibody, we showed that endogenous Sort1 was phosphorylated at S825 adjacent to the DXXLL sorting motif on the cytoplasmic tail. We demonstrated that mutagenesis that abolished Sort1 S825 phosphorylation decreased insulin-stimulated Sort1 localization on the plasma membrane and Sort1 protein stability in 3T3-L1 adipocytes. However, endogenous Sort1 phosphorylation at S825 was not affected by insulin stimulation or by inhibition of PI3K. In conclusion, this study revealed an important role of insulin signaling in regulating adipose Sort1 protein stability, and further suggests that impaired insulin signaling may underlie reduced adipose Sort1 in obesity. The cellular events downstream of insulin/PI3K/AKT signaling that mediates insulin regulation of Sort1 stability requires further investigation.

Insulin resistance induces posttranslational hepatic sortilin 1 degradation in mice.

Insulin promotes hepatic apolipoprotein B100 (apoB100) degradation, whereas insulin resistance is a major cause of hepatic apoB100/triglyceride overproduction in type 2 diabetes. The cellular trafficking receptor sortilin 1 (Sort1) was recently identified to transport apoB100 to the lysosome for degradation in the liver and thus regulate plasma cholesterol and triglyceride levels. Genetic variation of SORT1 was strongly associated with cardiovascular disease risk in humans. The major goal of this study is to investigate the effect and molecular mechanism of insulin regulation of Sort1. Results showed that insulin induced Sort1 protein, but not mRNA, in AML12 cells. Treatment of PI3K or AKT inhibitors decreased Sort1 protein, whereas expression of constitutively active AKT induced Sort1 protein in AML12 cells. Consistently, hepatic Sort1 was down-regulated in diabetic mice, which was partially restored after the administration of the insulin sensitizer metformin. LC-MS/MS analysis further revealed that serine phosphorylation of Sort1 protein was required for insulin induction of Sort1 in a casein kinase 2-dependent manner and that inhibition of PI3K signaling or prevention of Sort1 phosphorylation accelerated proteasome-dependent Sort1 degradation. Administration of a PI3K inhibitor to mice decreased hepatic Sort1 protein and increased plasma cholesterol and triglyceride levels. Adenovirus-mediated overexpression of Sort1 in the liver prevented PI3K inhibitor-induced Sort1 down-regulation and decreased plasma triglyceride but had no effect on plasma cholesterol in mice. This study identified Sort1 as a novel target of insulin signaling and suggests that Sort1 may play a role in altered hepatic apoB100 metabolism in insulin-resistant conditions.

Fish oil and fenofibrate prevented phosphorylation-dependent hepatic sortilin 1 degradation in Western diet-fed mice.

Obesity and diabetes are associated with hepatic triglyceride overproduction and hypertriglyceridemia. Recent studies have found that the cellular trafficking receptor sortilin 1 (Sort1) inhibits hepatic apolipoprotein B secretion and reduces plasma lipid levels in mice, and its hepatic expression was negatively associated with plasma lipids in humans. This study investigated the regulation of hepatic Sort1 under diabetic conditions and by lipid-lowering fish oil and fenofibrate. Results showed that hepatic Sort1 protein, but not mRNA, was markedly lower in Western diet-fed mice. Knockdown of hepatic Sort1 increased plasma triglyceride in mice. Feeding mice a fish oil-enriched diet completely restored hepatic Sort1 levels in Western diet-fed mice. Fenofibrate also restored hepatic Sort1 protein levels in Western diet-fed wild type mice, but not in peroxisome proliferator-activated receptor α (PPARα) knock-out mice. PPARα ligands did not induce Sort1 in hepatocytes in vitro. Instead, fish oil and fenofibrate reduced circulating and hepatic fatty acids in mice, and n-3 polyunsaturated fatty acids prevented palmitate inhibition of Sort1 protein in HepG2 cells. LC/MS/MS analysis revealed that Sort1 phosphorylation at serine 793 was increased in obese mice and in palmitate-treated HepG2 cells. Mutations that abolished phosphorylation at Ser-793 increased Sort1 stability and prevented palmitate inhibition of Sort1 ubiquitination and degradation in HepG2 cells. In summary, therapeutic strategies that prevent posttranslational hepatic Sort1 down-regulation in obesity and diabetes may be beneficial in improving dyslipidemia.

X-ray emission spectroscopy and density functional study of CO/Fe(100).

We report x-ray emission and absorption spectroscopy studies of the electronic structure of the predissociative α(3) phase of CO bound at hollow sites of Fe(100) as well as of the on-top bound species in the high-coverage α(1) phase. The analysis is supported by density functional calculations of structures and spectra. The bonding of "lying down" CO in the hollow site is well described in terms of π to π∗ charge transfer made possible through bonding interaction also at the oxygen in the minority spin-channel. The on-top CO in the mixed, high-coverage α(1) phase is found to be tilted due to adsorbate-adsorbate interaction, but still with bonding mainly characteristic of "vertical" on-top adsorbed CO similar to other transition-metal surfaces.

Crystal-facet and microstructure engineering in ZnO for photocatalytic NO oxidation.

Photocatalysis is believed to be an important way of reducing NO pollutant in air and the facet engineering of semiconducting oxides could enhance the efficiency of the photocatalysis. ZnO nanoparticles with different exposed crystalline facets were successfully synthesized using a hydrothermal method and their photocatalytic degradation towards NO was investigated. The crystals from ZnCl2 precursor were hexagonal mesoporous ones with exposed (0002) facet, while those from zinc acetate were in the form of flakes or wheat ears with enhanced exposure of (101(-)1) facet. Calcination in air imparted an enhanced the textural coefficient of the orientated facets as well as the oxygen defects. The nanocrystals with enhanced (0002) facet and lower flat-band energy did better in photoelectrochemical water-oxidation than those with exposed (101(-)1) facet that showed superior photocatalytic activity (approaching 76.7 ± 0.6% under 365 nm photons) for NO oxidation. According to theoretical calculations, (101(-)1) facet with O termination showed much higher affinity to NO molecules than other configurations, and the oxygen vacancy in ZnO played an minor role in the photocatalytic oxidation of NO. A high quantum efficiency approaching 97.5 ± 1.4% under 275 nm photons was obtained for the ZnO crystals from zinc acetate with mixed (0002) and (101(-)1) facets. This research explores the special characteristics of ZnO with different exposed facets and is important for the future design of highly efficient photocatalyst for hazardous material removal.

Rationalized design of hyperbranched trans-scale graphene arrays for enduring high-energy lithium metal batteries.

Lithium (Li) metal anode have shown exceptional potential for high-energy batteries. However, practical cell-level energy density of Li metal batteries is usually limited by the low areal capacity (<3 mAh cm-2) because of the accelerated degradation of high-areal capacity Li metal anodes upon cycling. Here, we report the design of hyperbranched vertical arrays of defective graphene for enduring deep Li cycling at practical levels of areal capacity (>6 mAh cm-2). Such atomic-to-macroscopic trans-scale design is rationalized by quantifying the degradation dynamics of Li metal anodes. High-energy Li metal cells are prototyped under realistic conditions with high cathode capacity (>4 mAh cm-2), low negative-to-positive electrode capacity ratio (1:1), and low electrolyte-to-capacity ratio (5 g Ah-1), which shed light on a promising move toward practical Li metal batteries.

Pelvic reconstruction and lateral prostate capsule sparing techniques improve early continence of robot-assisted radical cystectomy with orthotopic ileal neobladder.

PURPOSE: To evaluate urinary outcomes of pelvic construction and lateral capsule sparing techniques in robot-assisted radical cystectomy with orthotopic ileal neobladder (RARC-OIN). METHODS: A total of 107 male patients who underwent RARC-OIN during January 2017 and February 2021 in Sun Yat-sen Memorial Hospital were analyzed retrospectively. Standard RARC-OIN with or without nerve sparing technique was performed in 44 patients (standard group), lateral prostate capsule sparing technique was performed in 20 patients (LCS group), combined pelvic reconstruction (CPR) technique including anterior suspension and posterior reconstruction were performed in 43 patients (CPR group). The urinary function was assessed by the use of pads and the Bladder Cancer Index (BCI). Continence was defined as the use of 0-1 pad during daytime or night-time. RESULTS: There was no statistical difference between the three groups regarding demographic, perioperative, and pathological data. Continence rates were 6.8, 50.0 and 34.9% for daytime, 4.6, 40.0 and 32.6% for night-time in the standard group, LCS group and CPR group at 1 month post-operation, respectively. Continence rates were 34.1, 80.0 and 69.8% for daytime, 27.3, 75.0 and 65.1% for night-time in the standard group, LCS group and CPR group at 3 month post-operation, respectively. No statistically significant difference was observed in the daytime and night-time continence rates at 12 months. CONCLUSIONS: Lateral capsule-sparing and combined pelvic reconstruction techniques are feasible to improve early daytime and night-time continence rates in RARC with orthotopic neobladder. CLINICAL TRIAL REGISTRATION: The trial registration number: ChiCTR2100047606.

Atomic Bonding and Electronic Binding Energy of Two-Dimensional Bi/Li(110) Heterojunctions via BOLS-BB Model.

Combining the bond-order-length-strength (BOLS) and atomic bonding and electronic model (BB model) with density functional theory (DFT) calculations, we studied the atomic bonding and electronic binding energy behavior of Bi atoms adsorbed on the Li(110) surface. We found that the Bi atoms adsorbed on the Li(110) surface form two-dimensional (2D) geometric structures, including letter-, hexagon-, galaxy-, crown-, field-, and cobweb-shaped structures. Thus, we obtained the following quantitative information: (i) the field-shaped structure can be considered the bulk structure; (ii) the field-shaped structure of Bi atom formation has a 5d energy level of 22.727 eV, and in the letter shape structure, this energy is shifted to values greater than 0.342 eV; and (iii) the Bi/Li(110) heterojunction transfers charge from the inner Li atomic layer to the outermost Bi atomic layer. In addition, we analyzed the bonding and electronic dynamics involved in the formation of the Bi/Li(110) heterojunctions using residual density of states. This work provides a theoretical reference for the fine tuning of binding energies and chemical bonding at the interfaces of 2D metallic materials.

(GeTe)1-x(AgSnSe2)x: Strong Atomic Disorder-Induced High Thermoelectric Performance near the Ioffe-Regel Limit.

In thermoelectrics, the material's performance stems from a delicate tradeoff between atomic order and disorder. Generally, dopants and thus atomic disorder are indispensable for optimizing the carrier concentration and scatter short-wavelength heat-carrying phonons. However, the strong disorder has been perceived as detrimental to the semiconductor's electrical conductivity owing to the deteriorated carrier mobility. Here, we report the sustainable role of strong atomic disorder in suppressing the detrimental phase transition and enhancing the thermoelectric performance in GeTe. We found that AgSnSe2 and Sb co-alloying eliminates the unfavorable phase transition due to the high configurational entropy and achieve the cubic Ge1-x-ySbyTe1-x(AgSnSe2)x solid solutions with cationic and anionic site disorder. Though AgSnSe2 substitution drives the carrier mean free path toward the Ioffe-Regel limit and minimizes the carrier mobility, the increased carrier concentration could render a decent electrical conductivity, affording enough phase room for further performance optimization. Given the lowermost carrier mean free path, further Sb alloying on Ge sites was implemented to progressively optimize the carrier concentration and enhance the density-of-state effective mass, thereby substantially enhancing the Seebeck coefficient. In addition, the high density of nanoscale strain clusters induced by strong atomic disorders significantly restrains the lattice thermal conductivity. As a result, a state-of-the-art zT ≈ 1.54 at 773 K was attained in cubic Ge0.58Sb0.22Te0.8(AgSnSe2)0.2. These results demonstrate that the strong atomic disorder at the high entropy scale is a previously underheeded but promising approach in thermoelectric material research, especially for the numerous low carrier mobility materials.

Medium Entropy-Enabled High Performance Cubic GeTe Thermoelectrics.

The configurational entropy is an emerging descriptor in the functional materials genome. In thermoelectric materials, the configurational entropy helps tune the delicate trade-off between carrier mobility and lattice thermal conductivity, as well as the structural phase transition, if any. Taking GeTe as an example, low-entropy GeTe generally have high carrier mobility and distinguished zT > 2, but the rhombohedral-cubic phase transition restricts the applications. In contrast, despite cubic structure and ultralow lattice thermal conductivity, the degraded carrier mobility leads to a low zT in high-entropy GeTe. Herein, medium-entropy alloying is implemented to suppress the phase transition and achieve the cubic GeTe with ultralow lattice thermal conductivity yet decent carrier mobility. In addition, co-alloying of (Mn, Pb, Sb, Cd) facilitates multivalence bands convergence and band flattening, thereby yielding good Seebeck coefficients and compensating for decreased carrier mobility. For the first time, a state-of-the-art zT of 2.1 at 873 K and average zT ave of 1.3 between 300 and 873 K are attained in cubic phased Ge0.63Mn0.15Pb0.1Sb0.06Cd0.06Te. Moreover, a record-high Vickers hardness of 270 is attained. These results not only promote GeTe materials for practical applications, but also present a breakthrough in the burgeoning field of entropy engineering.

Intrinsic Endocardial Defects Contribute to Hypoplastic Left Heart Syndrome.

Hypoplastic left heart syndrome (HLHS) is a complex congenital heart disease characterized by abnormalities in the left ventricle, associated valves, and ascending aorta. Studies have shown intrinsic myocardial defects but do not sufficiently explain developmental defects in the endocardial-derived cardiac valve, septum, and vasculature. Here, we identify a developmentally impaired endocardial population in HLHS through single-cell RNA profiling of hiPSC-derived endocardium and human fetal heart tissue with an underdeveloped left ventricle. Intrinsic endocardial defects contribute to abnormal endothelial-to-mesenchymal transition, NOTCH signaling, and extracellular matrix organization, key factors in valve formation. Endocardial abnormalities cause reduced cardiomyocyte proliferation and maturation by disrupting fibronectin-integrin signaling, consistent with recently described de novo HLHS mutations associated with abnormal endocardial gene and fibronectin regulation. Together, these results reveal a critical role for endocardium in HLHS etiology and provide a rationale for considering endocardial function in regenerative strategies.

Synergistic effect of internal electric field and oxygen vacancy on the photocatalytic activity of BiOBrxI1-x with isomorphous fluorine substitution.

Recently, bismuth oxyhalide photocatalysts have attracted much attention owing to their unique layered structure. In this paper, fluorine isomorphously substituted BiOBrxI1-x solid solution was synthesized by controlling the molar ratios of F, Br and I elements by the chemical precipitation method at room temperature. It was found that BiOF0.4Br0.5I0.1 exhibited excellent photocatalytic activity for the degradation of methyl orange, which was 10.1, 5.0 and 4.3 times higher than that of BiOI, BiOBr and BiOBr0.9I0.1 under visible light irradiation, respectively. It could be inferred that fluorine substitution is favorable to enhance the internal electric field (IEF) for BiOBrxI1-x with layered structure, which could improve the separation efficiency of the photogenerated holes and electrons and thus enhance the photocatalytic activity. On the other hand, the concentration of oxygen vacancies (OVs) rose with the increase of fluorine content, which could facilitate the adsorption of pollutants and serve as trapping sites for photo-induced carriers to improve the photocatalytic activity. The finding provides new insights into the synergistic effect of IEF and OVs toward the construction of high efficient photocatalysts.