ENU-based dominant genetic screen identifies contractile and neuronal gene mutations in congenital heart disease.

BACKGROUND: Congenital heart disease (CHD) is the most prevalent congenital anomaly, but its underlying causes are still not fully understood. It is believed that multiple rare genetic mutations may contribute to the development of CHD. METHODS: In this study, we aimed to identify novel genetic risk factors for CHD using an ENU-based dominant genetic screen in mice. We analyzed fetuses with malformed hearts and compared them to control littermates by whole exome or whole genome sequencing (WES/WGS). The differences in mutation rates between observed and expected values were tested using the Poisson and Binomial distribution. Additionally, we compared WES data from human CHD probands obtained from the Pediatric Cardiac Genomics Consortium with control subjects from the 1000 Genomes Project using Fisher's exact test to evaluate the burden of rare inherited damaging mutations in patients. RESULTS: By screening 10,285 fetuses, we identified 1109 cases with various heart defects, with ventricular septal defects and bicuspid aortic valves being the most common types. WES/WGS analysis of 598 cases and 532 control littermates revealed a higher number of ENU-induced damaging mutations in cases compared to controls. GO term and KEGG pathway enrichment analysis showed that pathways related to cardiac contraction and neuronal development and functions were enriched in cases. Further analysis of 1457 human CHD probands and 2675 control subjects also revealed an enrichment of genes associated with muscle and nervous system development in patients. By combining the mice and human data, we identified a list of 101 candidate digenic genesets, from which each geneset was co-mutated in at least one mouse and two human probands with CHD but not in control mouse and control human subjects. CONCLUSIONS: Our findings suggest that gene mutations affecting early hemodynamic perturbations in the developing heart may play a significant role as a genetic risk factor for CHD. Further validation of the candidate gene set identified in this study could enhance our understanding of the complex genetics underlying CHD and potentially lead to the development of new diagnostic and therapeutic approaches.

Vertically Fluorinated Graphene Encapsulated SiOx Anode for Enhanced Li+ Transport and Interfacial Stability in High-Energy-Density Lithium Batteries.

Achieving high energy density has always been the goal of lithium-ion batteries (LIBs). SiOx has emerged as a compelling candidate for use as a negative electrode material due to its remarkable capacity. However, the huge volume expansion and the unstable electrode interface during (de)lithiation, hinder its further development. Herein, we report a facile strategy for the synthesis of surface fluorinated SiOx (SiOx@vG-F), and investigate their influences on battery performance. Systematic experiments investigations indicate that the reaction between Li+ and fluorine groups promotes the in-situ formation of stable LiF-rich solid electrolyte interface (SEI) on the surface of SiOx@vG-F anode, which effectively suppresses the pulverization of microsized SiOx particles during the charge and discharge cycle. As a result, the SiOx@vG-F enabled a higher capacity retention of 86.4% over 200 cycles at 1.0 C in the SiOx@vG-F||LiNi0.8Co0.1Mn0.1O2 full cell. This approach will provide insights for the advancement of alternative electrode materials in diverse energy conversion and storage systems.

How health seeking behavior develops in patients with type 2 diabetes: a qualitative study based on health belief model in China.

Background: Type 2 diabetes(T2DM) is a global health problem which is accompanied with multi-systemic complications, and associated with long-term health burden and economic burden. Effective health seeking behavior (HSB) refers to reasonably utilize health resources, effectively prevent and treat diseases, and maintain health. Effective health seeking behavior (HSB) is vital to mitigate the risk of T2DM complications. However, health seeking behavior for T2DM patients remains sub-optimal worldwide. Objective: The study aimed to explore the internal logic of how health seeking behavior of T2DM patients develops and the influencing factors of health seeking behavior. With a view to provide a reference basis for improving the health seeking behavior situation of T2DM patients. Methods: This study was conducted at an integrated tertiary hospital in China. People who were diagnosed with T2DM, capable of expressing clearly and had no mental illness, were approached based on a purposive sampling. The experience of T2DM and health seeking behavior were collected via in-depth interviews. A theory-driven thematic analysis based on Health Belief Model (HBM) was applied for data analysis. Inductive reasoning was used to identify emerging themes which were not included in HBM. Results: 26 patients with T2DM were included in the current study. Seven themes were identified, including: (1) T2DM diagnosis and severity; (2) T2DM treatment and management; (3) Perceived susceptibility of diabetes progression; (4) Perceived severity of diabetes progression; (5) Perceived benefits of health seeking behavior; (6) Perceived barriers of health seeking behavior; (7) Perception of behavioral cues. Generally, patients with T2DM lacked reliable sources of information, considered T2DM to be slow-progressing and without posing an immediate threat to life. Consequently, they did not fully grasp the long-term risks associated with T2DM or the protective effects of health seeking behavior. Conclusion: This study highlighted the challenges in health seeking behavior for patients with T2DM. It suggested that future interventions and strategies should involve multi-faceted approaches, targeting healthcare providers (HCPs), patients with T2DM, and their support networks. This comprehensive strategy can help patients better understand their condition and the importance of effective health seeking behavior. Ultimately, enhancing their capacity for adopting appropriate health-seeking practices.

Intrarenal pH-Responsive Self-Assembly of Luminescent Gold Nanoparticles for Diagnosis of Early Kidney Injury.

Metabolic acidosis-induced kidney injury (MAKI) is asymptomatic and lack of clinical biomarkers in early stage, but rapidly progresses to severe renal fibrosis and ultimately results in end-stage kidney failure. Therefore, developing rapid and noninvasive strategies direct responsive to renal tubular acidic microenvironment rather than delayed biomarkers are essential for timely renoprotective interventions. Herein, we develop pH-responsive luminescent gold nanoparticles (p-AuNPs) in the second near-infrared emission co-coated with 2,3-dimethylaleic anhydride conjugated ß-mercaptoethylamine and cationic 2-diethylaminoethanethiol hydrochloride, which showed sensitive pH-induced charge reversal and intrarenal self-assembly for highly sensitive and long-time (~24 h) imaging of different stages of MAKI. By integrating advantages of pH-induced intrarenal self-assembly and enhanced interactions between pH-triggered positively charged p-AuNPs and renal tubular cells, the early- and late-stage MAKI could be differentiated rapidly within 10 min post-injection (p.i.) with contrast index (CI) of 3.5 and 4.3, respectively. The corresponding maximum CI could reach 5.1 and 9.2 at 12 h p.i., respectively. Furthermore, p-AuNPs were demonstrated to effectively real-time monitor progressive recovery of kidney injury in MAKI mice after therapy, and also exhibit outstanding capabilities for drug screening. This pH-responsive strategy showed great promise for feedback on kidney dysfunction progression, opening new possibilities for early-stage diagnosis of pH-related diseases.

Noncovalent Interaction Guided Precise Photoluminescence Regulation of Gold Nanoclusters in Both Isolate Species and Aggregate States.

Designing luminophores bright in both isolate species and aggregate states is of great importance in many emerging cutting-edge applications. However, the conventional luminophores either emit in isolate species but quench in aggregate state or emit in aggregate state but darken in isolate species. Here we demonstrate that the precise regulation of noncovalent interactions can realize luminophores bright in both isolate species and aggregate states. It is firstly discovered that the intra-cluster interaction enhances the emission of atomically precise Au25(pMBA)18 (pMBA=4-mercaptobenzoic acid), a nanoscale luminophore, while the inter-cluster interaction quenches the emission. The emission enhancing strategies are then well-designed by both introducing exogenous substances to block inter-cluster interaction and surface manipulation of Au25(pMBA)18 at the molecular level to enhance intra-cluster interaction, opening new possibilities to controllably enhance the luminophore's photoluminescence in both isolate species and aggregate states in different phases including aqueous solution, solid state and organic solvents.

A Fully Amorphous, Dynamic Cross-Linked Polymer Electrolyte for Lithium-Sulfur Batteries Operating at Subzero-Temperatures.

Solid-state lithium-sulfur batteries have shown prospects as safe, high-energy electrochemical storage technology for powering regional electrified transportation. Owing to limited ion mobility in crystalline polymer electrolytes, the battery is incapable of operating at subzero temperature. Addition of liquid plasticizer into the polymer electrolyte improves the Li-ion conductivity yet sacrifices the mechanical strength and interfacial stability with both electrodes. In this work, we showed that by introducing a spherical hyperbranched solid polymer plasticizer into a Li+ -conductive linear polymer matrix, an integrated dynamic cross-linked polymer network was built to maintain fully amorphous in a wide temperature range down to subzero. A quasi-solid polymer electrolyte with a solid mass content >90 % was prepared from the cross-linked polymer network, and demonstrated fast Li+ conduction at a low temperature, high mechanical strength, and stable interfacial chemistry. As a result, solid-state lithium-sulfur batteries employing the new electrolyte delivered high reversible capacity and long cycle life at 25 °C, 0 °C and -10 °C to serve energy storage at complex environmental conditions.

Luminescent Gold Nanoparticles with Discrete DNA Valences for Precisely Controlled Transport at the Subcellular Level.

Ultrasmall luminescent gold nanoparticles (AuNPs) with excellent capabilities to cross biological barriers offer great promise in designing intelligent model nanomedicines for investigating structure-property relationships at the subcellular level. However, the strict surface controllability of ultrasmall AuNPs is challenging because of their small size. Herein, we report a facile in situ method for precisely controlling DNA aptamer valences on the surface of luminescent AuNPs with emission in the second near-infrared window using a phosphorothioate-modified DNA aptamer, AS1411, as a template. The discrete DNA aptamer number of AS1411-functionalized AuNPs (AS1411-AuNPs, ≈1.8 nm) with emission at 1030 nm was controlled in one aptamer (V1), two aptamers (V2), and four aptamers (V4). It was then discovered that not only the tumor-targeting efficiencies but also the subcellular transport of AS1411-AuNPs were precisely dependent on valences. A slight increase in valence from V1 to V2 increased tumor-targeting efficiencies and resulted in higher nucleus accumulation, whereas a further increase in valence (e.g., V4) significantly increased tumor-targeting efficiencies and led to higher cytomembrane accumulation. These results provide a basis for the strict surface control of nanomedicines in the precise regulation of in vivo transport at the subcellular level and their translation into clinical practice in the future.

Effect of Grafting Conditions on the Interfacial Properties of Silane Modified Wood Veneer/PE Film Plywood.

In order to elucidate the importance of grafting in the compatibilization process of silane coupling agents, poplar veneer was treated with silane coupling agents and grafted under different heating conditions. The treated veneers were used composited with PE film to prepare different plywood samples. XPS and WCA were used to analyze the effect of grafting conditions on the surface properties of the silane-treated veneer. The results showed that free silanols can physically be adsorbed onto all silane-treated veneer surfaces, forming hydrogen-Si-O-Si- bonds and therefore increasing the water contact angle. Only under heating conditions could the -Si-O-Si- be converted into covalent -Si-O-C- bonds, which helped to improve the bonding strength. When silane-treated veneer was grafted at 120 °C for 90 min, the tensile shear strength of plywood reached 1.03 MPa, meeting the requirements of GB/T 9846.3-2004 for outdoor materials. Enhanced interlock between silane-modified veneer and PE film was observed under the optimal grafting condition by SEM. The better interface structure allowed improvement of thermal stability. DMA results showed that the retention rate in storage modulus at 130 °C was 60% for the grafted sample, while the retention rate for the ungrafted sample was only 31%.

"Pore-Hopping" Ion Transport in Cellulose-Based Separator Towards High-Performance Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) have great potential for large-scale energy storage. Cellulose is an attractive material for sustainable separators, but some key issues still exist affecting its application. Herein, a cellulose-based composite separator (CP@PPC) was prepared by immersion curing of cellulose-based separators (CP) with poly(propylene carbonate) (PPC). With the assistance of PPC, the CP@PPC separator is able to operate the cell stably at high voltages (up to 4.95 V). The "pore-hopping" ion transport mechanism in CP@PPC opens up extra Na+ migration paths, resulting in a high Na+ transference number (0.613). The separator can also tolerate folding, bending and extreme temperature under certain circumstances. Full cells with CP@PPC reveal one-up capacity retention (96.97 %) at 2C after 500 cycles compared to cells with CP. The mechanism highlights the merits of electrolyte analogs in separator modification, making a rational design for durable devices in advanced energy storage systems.

Advanced Covalent Organic Frameworks for Multi-Valent Metal Ion Batteries.

Covalent organic frameworks (COFs) have received increased interest in recent years as an advanced class of materials. By virtue of the available monomers, multiple conformations and various linkages, COFs offer a wide range of opportunities for complex structural design and specific functional development of materials, which has facilitated the widespread application in many fields, including multi-valent metal ion batteries (MVMIBs), described as the attractive candidate replacing lithium-ion batteries (LIBs). With their robust skeletons, diverse pores, flexible structures and abundant functional groups, COFs are expected to help realize a high performance MVMIBs. In this review, we present an overview of COFs, describe advances in topology design and synthetic reactions, and study the application of COFs in MVMIBs, as well as discuss challenges and solutions in the preparation of COFs electrodes, in the hope of providing constructive insights into the future direction of COFs.

Multifunctional Carbon Modification Enhancement for Vanadium-Based Phosphates as an Advanced Cathode of Zinc-Ion Batteries.

In recent years, rechargeable aqueous zinc-ion batteries (ZIBs) have shown extraordinary potential due to their safety, nontoxicity, sustainable zinc resources, and low price. However, the lack of suitable cathode materials hinders the development of ZIBs. Recently, layered phosphates have been widely used as cathode materials. As one typical phosphate cathode, vanadium oxyphosphate (VOPO4) has inherently low electronic conductivity and structural dissolution in electrochemical reactions, limiting its development. To solve these problems, VOPO4/C is prepared by combining multifunctional carbon material with a VOPO4 interlayer and an external surface, which not only improves the electronic conductivity of the composite material but also effectively inhibits the dissolution of VOPO4 in the electrolyte. As a result, the prepared VOPO4/C could deliver a reversible capacity of 140 mA h g-1 at a current density of 100 mA g-1. Furthermore, the rate performance of the VOPO4/C composite has also been improved significantly. In the process of charging and discharging, zinc ions in the composite show perfect intercalate and deintercalate performance.

Regulating the Li Nucleation/Growth Behavior via Cu2O Nanowire Array and Artificial Solid Electrolyte Interphase toward Highly Stable Li Metal Anode.

Lithium (Li) metal has been considered to be the most promising anode material for next-generation rechargeable batteries. Unfortunately, the hazards induced by dendrite growth and volume fluctuation hinder its commercialized application. Here, a three-dimensional (3D) current collector composed of a vertically aligned Cu2O nanowire that is tightly coated with a polydopamine protective layer is developed to solve the encountered issues of lithium metal batteries (LMBs). The Cu2O nanowire arrays (Cu2O NWAs) provide abundant lithiophilic sites for inducing Li nucleation selectively to form a thin Li layer around the nanowires and direct subsequent Li deposition. The well-defined nanochannel works well in confining the Li growth spatially and buffering the volume change during the repeated cycling. The PDA coatings adhered onto the outline of the Cu2O NWAs serve as the artificial solid electrolyte interface to isolate the electrode and electrolyte and retain the interfacial stability. Moreover, the increased specific area of copper foam (CF) can dissipate the local current density and further suppress the growth of Li dendrites. As a result, CF@Cu2O NWAs@PDA realizes a dendrite-free morphology and the assembled symmetrical batteries can work stably for over 1000 h at 3 mA cm-2. When CF@Cu2O NWAs@PDA is coupled with a LiFePO4 cathode, the full cells exhibit improved cycle stability and rate performance.

Covalent Organic Framework with Highly Accessible Carbonyls and π-Cation Effect for Advanced Potassium-Ion Batteries.

Covalent organic frameworks (COF) possess a robust and porous crystalline structure, making them an appealing candidate for energy storage. Herein, we report an exfoliated polyimide COF composite (P-COF@SWCNT) prepared by an in situ condensation of anhydride and amine on the single-walled carbon nanotubes as advanced anode for potassium-ion batteries (PIBs). Numerous active sites exposed on the exfoliated frameworks and the various open pathways promote the highly efficient ion diffusion in the P-COF@SWCNT while preventing irreversible dissolution in the electrolyte. During the charging/discharging process, K+ is engaged in the carbonyls of imide group and naphthalene rings through the enolization and π-K+ effect, which is demonstrated by the DFT calculation and XPS, ex-situ FTIR, Raman. As a result, the prepared P-COF@SWCNT anode enables an incredibly high reversible specific capacity of 438 mA h g-1 at 0.05 A g-1 and extended stability. The structural advantage of P-COF@SWCNT enables more insights into the design and versatility of COF as an electrode.

Ultrasmall Luminescent Metal Nanoparticles: Surface Engineering Strategies for Biological Targeting and Imaging.

In the past decade, ultrasmall luminescent metal nanoparticles (ULMNPs, d < 3 nm) have achieved rapid progress in addressing many challenges in the healthcare field because of their excellent physicochemical properties and biological behaviors. With the sharp shrinking size of large plasmonic metal nanoparticles (PMNPs), the contributions from the surface characteristics increase significantly, which brings both opportunities and challenges in the application-driven surface engineering of ULMNPs toward advanced biological applications. Here, the systematic advancements in the biological applications of ULMNPs from bioimaging to theranostics are summarized with emphasis on the versatile surface engineering strategies in the regulation of biological targeting and imaging performance. The efforts in the surface functionalization strategies of ULMNPs for enhanced disease targeting abilities are first discussed. Thereafter, self-assembly strategies of ULMNPs for fabricating multifunctional nanostructures for multimodal imaging and nanomedicine are discussed. Further, surface engineering strategies of ratiometric ULMNPs to enhance the imaging stability to address the imaging challenges in complicated bioenvironments are summarized. Finally, the phototoxicity of ULMNPs and future perspectives are also reviewed, which are expected to provide a fundamental understanding of the physicochemical properties and biological behaviors of ULMNPs to accelerate their future clinical applications in healthcare.

[Co3(µ3-O)]-Based Metal-Organic Frameworks as Advanced Anode Materials in K- and Na-Ion Batteries.

A new metal-organic framework {(Me2NH2)2[Co3(µ3-O)(btb)2(py)(H2O)]·(DMF)2(H2O)2}n (Cobtbpy) was solvothermal synthesized (H3btb = 1,3,5-tri(4-carboxylphenyl)benzene, py = pyridine, DMF = N,N-dimethylformamide). Cobtbpy shows a (3,6)-connected rtl 3D network with a point symbol of (4·62)2(42·610·83) based on the [Co3(µ3-O)] clusters. The obtained Cobtbpy has stable, accessible, dense active sites and can be applied in the potassium- and sodium-ion batteries. Through mixing with single-walled carbon nanotubes, the prepared composite anode material Cobtbpy-0.9 achieved a high reversible capability, delivering 416 mAh/g in the potassium-ion batteries and 379 mAh/g in the sodium-ion batteries at 0.05 A/g. The outstanding properties of Cobtbpy-0.9 in the batteries demonstrated that this MOFs-based carbon composite is a highly desirable electrode material candidate for high-performance potassium- and sodium-ion batteries.

Regulation of Cathode-Electrolyte Interphase via Electrolyte Additives in Lithium Ion Batteries.

As the power supply of the prosperous new energy products, advanced lithium ion batteries (LIBs) are widely applied to portable energy equipment and large-scale energy storage systems. To broaden the applicable range, considerable endeavours have been devoted towards improving the energy and power density of LIBs. However, the side reaction caused by the close contact between the electrode (particularly the cathode) and the electrolyte leads to capacity decay and structural degradation, which is a tricky problem to be solved. In order to overcome this obstacle, the researchers focused their attention on electrolyte additives. By adding additives to the electrolyte, the construction of a stable cathode-electrolyte interphase (CEI) between the cathode and the electrolyte has been proven to competently elevate the overall electrochemical performance of LIBs. However, how to choose electrolyte additives that match different cathode systems ideally to achieve stable CEI layer construction and high-performance LIBs is still in the stage of repeated experiments and exploration. This article specifically introduces the working mechanism of diverse electrolyte additives for forming a stable CEI layer and summarizes the latest research progress in the application of electrolyte additives for LIBs with diverse cathode materials. Finally, we tentatively set forth recommendations on the screening and customization of ideal additives required for the construction of robust CEI layer in LIBs. We believe this minireview will have a certain reference value for the design and construction of stable CEI layer to realize desirable performance of LIBs.

Bidirectional Regulation of Singlet Oxygen Generation from Luminescent Gold Nanoparticles through Surface Manipulation.

Singlet oxygen (1 O2 ) generation has been observed from ultrasmall luminescent gold nanoparticles (AuNPs), but regulation of 1 O2 generation ability from the nanosized noble metals has remained challenging. Herein, the 1 O2 generation ability of ultrasmall AuNPs (d ≈ 1.8 nm) is reported to be highly correlated to the surface factors including the amount of Au(I) species and surface charge. By taking the advantages of facile in situ PEGylation, it is discovered that a high amount of Au(I) species and surface charge results in strong ability in generation of 1 O2 , whereas a relative low amount of Au(I) species and surface charge leads to weak ability in 1 O2 production. A feasible general strategy is then developed to controllably regulate the 1 O2 generation efficiency of the AuNPs through facile ligand exchange with positively-charged or negatively-charged thiolated ligands. The AuNPs as nanophotosensitizer for 1 O2 generation in the cellular level is also demonstrated to be highly controllable through surface ligand exchange with synergistical effects of 1 O2 generation ability and subcellular distribution to lysosome or mitochondria. The strategy in the bidirectional regulation of 1 O2 generation from ultrasmall AuNPs provides guidance for future design of nanosized metal nanomedicine toward specific disease diagnosis and treatment.

The complete mitochondrial genome sequence of Symphysodon discus Heckel (1840).

The complete mitochondrial genome of Symphysodon discus Heckel was 16 544 bp in length, consisting of 22 tRNA genes, 13 protein-coding genes, 2 ribosomal rRNA genes, and a control region or displacement loop (D-loop). With the exception of 8 tRNAs and ND6 genes, the others were encoded on H-strand. The base composition on H-strand was 30.04% C, 28.39% A, 26.49% T and 15.07% G, exhibiting an A + T rich pattern. The codon usage was consistent with the other vertebrate mitochondrial pattern, i.e. start codon is ATG or GTG and stop codons are TAA, TAG or T- -. Stop codon TAG was only found in the ND6. There were 8 regions of gene overlapped with the length of 26 bp in total and 12 intergenic spacer regions (99 bp in total).