Building 3D Crosslinked Graphene-MXene Nanoarchitectures Decorated with MoS2 Quantum Dots Enables Efficient Electrocatalytic Hydrogen Evolution.

Although MoS2 quantum dots with abundant edge sites have been regarded as promising eletrode materials for the hydrogen evolution reaction (HER), their electrocatalytic capacity still requires improvements in actual applications. Herein. we demonstrate a controllable and robust bottom-up approach to build 3D crosslinked graphene-Ti3C2Tx MXene frameworks decorated with MoS2 quantum dots (MQD/RGO-MX) via a convenient co-assembly process. The novel structural design gives the MQD/RGO-MX nanoarchitectures a series of superior textural attributes, including 3D interconnected networks, continuous meso- and macropores, well-dispersed quantum dots, ameliorative electronic configuration, and excellent electrical conductivity. Accordingly, the resulting hybrid nanoarchitectures express superior electrocatalytic properties in terms of a low onset potential of only 45 mV, a small Tafel slope of 61 mV dec-1 as well as a long service life towards the HER, which make it quite competitive against bare MoS2 quantum dots, MXene as well as binary MQD/RGO and MQD/MXene electrocatalysts.

The Pharmacokinetics and Liver-Targeting Evaluation of Silybin Liposomes Mediated by the NTCP/OCTN2 Dual Receptors.

The disadvantage of a traditional dosage regimen is the inability to deliver a sufficient drug concentration to the lesion site, which can result in adverse side effects due to nonspecific drug delivery. Actively targeting hepatic cells is a promising therapeutic strategy for liver disease. In this study, l-carnitine and a targeting peptide derived from the hepatitis B virus large envelope protein were used to modify liposomes for drug delivery to the liver through the sodium taurocholate cotransporting polypeptide (NTCP) and the organic cation/carnitine transporter 2 (OCTN2) receptors. Silybin was selected as the model drug. The solubility of silybin can reach 0.3 mg/mL after encapsulation in liposomes. The NTCP-specific and OCTN2-accelerated Myrcludex B and l-carnitine dual-modified liposomes were validated in vitro. The uptake of coumarin-6 in dual ligand-modified liposomes by hepatocytes was up to 2.36 µg/mg compared with unmodified liposomes (1.05 µg/mg). The pharmacokinetics and targeting abilities of various liposome formulations were evaluated in Kunming mice. Targeted liposomes increased the concentration of silybin and prolonged the drug's retention time in the liver. The area under the liver's pharmacokinetic curve of targeted liposomes was twice that of silybin injection, suggesting the promising application potential of silybin-loaded hepatotropic nanovesicles.

Mesoporous Hollow Carbon Sphere-Embedded MXene Architectures Decorated with Ultrafine Rh Nanocrystals toward Methanol Electrooxidation.

The development of advanced Pt-alternative anode electrocatalysts with high activity and reliable stability is critical to overcoming the technical challenges of direct methanol fuel cells. Here, we propose a robust bottom-up strategy for the spatial construction of mesoporous hollow carbon sphere (HCS)-embedded MXene architectures decorated with ultrafine Rh nanocrystals (Rh/HCS-MX) via stereoscopic coassembly reactions. The rational intercalation of HCS effectively separates the MXene nanowalls to achieve a rapid mass-transfer efficiency, while the intimate coupling of the hybrid carrier with Rh nanocrystals enables their electronic structure optimization, thus contributing to strong synergistic catalytic effects. Accordingly, the resulting Rh/HCS-MX architectures exhibit outstanding methanol electrooxidation properties in terms of large electrochemical active surface areas, high mass/specific activities, and good long-term stability, all of which are significantly superior to the traditional Rh/carbon black, Rh/HCS, and Rh/MXene as well as commercial Pt/carbon balck and Pd/carbon balck electrocatalysts.

Single-Atom Phosphorus Defects Decorated CoP Cocatalyst Boosts Photocatalytic Hydrogen Generation Performance of Cd0.5 Zn0.5 S by Directed Separating the Photogenerated Carriers.

Design and preparation of an efficient and nonprecious cocatalysts, with structural features and functionality necessary for improving photocatalytic performance of semiconductors, remain a formidable challenge until now. Herein, for the first time, a novel CoP cocatalyst with single-atom phosphorus vacancies defects (CoP-Vp ) is synthesized and coupled with Cd0.5 Zn0.5 S to build CoP-Vp @Cd0.5 Zn0.5 S (CoP-Vp @CZS) heterojunctions photocatalysts via a liquid phase corrosion method following by an in suit growth process. The nanohybrids deliver an attractive photocatalytic hydrogen production activity of 2.05 mmol h-1 30 mg-1 under visible-light irradiation, which is 14.66 times higher than that of the pristine ZCS samples. As expected, CoP-Vp further enhances the charge-separation efficiency of ZCS, in addition to the improvement of the electron transfer efficiency, which is confirmed by the ultrafast spectroscopies. Mechanism studies based on density functional theory calculations verify that Co atoms adjacent with single-atom Vp play the key role in translation, rotation, and transformation of electrons for H2 O reduction. This scalable strategy focusing defect engineering provides a new insight into designing the highly active cocatalysts to boost the photocatalytic application.

Phenotypic findings and pregnancy outcomes of fetal rare autosomal aneuploidies detected using chromosomal microarray analysis.

BACKGROUND: Aneuploidies are the most common chromosomal abnormality and the main genetic cause of adverse pregnancy outcomes. Since numerous studies have focused on common trisomies, relatively little is known about the association between phenotypic findings and rare autosomal aneuploidies (RAAs). We conducted a retrospective study of 48,904 cases for chromosomal microarray analysis in a large tertiary referral center and reported the overall frequencies, clinical manifestations, and outcomes of prenatal RAAs. RESULTS: A total of 90 RAAs were detected, of which 83 cases were mosaic trisomies and 7 were non-mosaic trisomies. Chromosomes 16, 22, and 9 were identified as the major chromosomes involving RAAs. The four predominant indications for prenatal diagnosis in our RAA cases were RAA-positive in noninvasive prenatal screening, advanced maternal age, ultrasound abnormalities, and high-risk for serum prenatal screening. Cardiovascular defects were the most frequently observed structural abnormalities, followed by musculoskeletal anomalies. Increased nuchal translucency and persistent left superior vena cava, the major soft marker abnormalities involved, were also observed in our RAA cases. Clinical outcomes were available for all RAAs, with 63 induced abortions and 27 live births recorded. CONCLUSIONS: Variable phenotypes and outcomes were observed, which were highly heterogeneous in cases of prenatal RAAs. Thus, a cautious and comprehensive strategy should be implemented during prenatal counseling for RAAs.

Spatial Relation Controllable Di-Defects Synergy Boosts Electrocatalytic Hydrogen Evolution Reaction over VSe2 Nanoflakes in All pH Electrolytes.

Defect engineering of transition metal dichalcogenides (TMDCs) is important for improving electrocatalytic hydrogen evolution reaction (HER) performance. Herein, a facile and scalable atomic-level di-defect strategy over thermodynamically stable VSe2 nanoflakes, yielding attractive improvements in the electrocatalytic HER performance over a wide electrolyte pH range is reported. The di-defect configuration with controllable spatial relation between single-atom (SA) V defects and single Se vacancy defects effectively triggers the electrocatalytic HER activity of the inert VSe2 basal plane. When employed as a cathode, this di-defects decorated VSe2 electrocatalyst requires overpotentials of 67.2, 72.3, and 122.3 mV to reach a HER current density of 10 mA cm-2 under acidic, alkaline, and neutral conditions, respectively, which are superior to most previously reported non-noble metal HER electrocatalysts. Theoretical calculations reveal that the reactive microenvironment consists of two adjacent SA Mo atoms with two surrounding symmetric Se vacancies, yielding optimal water dissociation and hydrogen desorption kinetics. This study provides a scalable strategy for improving the electrocatalytic activity of other TMDCs with inert atoms in the basal plane.

MXene Nanosheets Induce Efficient Iron Selenide Active Sites to Boost the Electrocatalytic Hydrogen Evolution Reaction.

Along with the widespread utilization of hydrogen energy, the rise of highly active hydrogen evolution electrocatalysts with affordable costs presently becomes a substantial crux of this emerging domain. In this work, we demonstrate a feasible and convenient in situ seed-induced growth strategy for the construction of small-sized FeSe2 nanoparticles decorated on two-dimensional (2D) superthin Ti3C2Tx MXene sheets (FeSe2/Ti3C2Tx) through a manipulated bottom-up synthetic procedure. By virtue of the distinctive 0D/2D heterostructures, abundant exposed surface area, well-distributed FeSe2 catalytic centers, strong surface electronic coupling, and high electrical conductivity, the resultant FeSe2/Ti3C2Tx nanoarchitectures are endowed with a superior electrocatalytic hydrogen evolution capacity including a competitive onset potential of 89 mV, a favorable Tafel slope of 78 mV dec-1, and a long-period stability, significantly better than that of the pristine FeSe2 and Ti3C2Tx catalysts.

LncMSEN1, a mantle-specific LncRNA participating in nacre formation and response to polyI:C stimulation in pearl oyster Pinctada fucata martensii.

Long noncoding RNA (LncRNA) regulates various life processes, including biomineralization and innate immune response through complex mechanisms. In this research, we identified a LncRNA named LncMSEN1 from pearl oyster Pinctada fucata martensii. LncMSEN1 sequence was validated by PCR, and its expression was high in mantle tissues according to qRT-PCR. LncMSEN1 was co-located with the nacre matrix protein N-U8 and fibrinogen domain-containing protein. And LncMSEN1 and N-U8 expression levels in the mantle were positively correlated. RNA interference was used to detect its effect on nacre formation in shells. Results showed that the decreased LncMSEN1 expression in mantle can cause the disordered growth of crystals on the inner surface of nacre in the shells, as well as the decrease expression of N-U8. In addition, the LncMSEN1 expression level significantly increased at 24 h after polyI:C stimulation in the mantle (P < 0.05). These findings suggested the involvement of LncMSEN1 in the formation of nacre in shells and related to innate immune response in pearl oyster, which provided additional insights into the roles of LncRNAs in pearl oysters.

Mutations in C1orf194, encoding a calcium regulator, cause dominant Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease is a hereditary motor and sensory neuropathy exhibiting great clinical and genetic heterogeneity. Here, the identification of two heterozygous missense mutations in the C1orf194 gene at 1p21.2-p13.2 with Charcot-Marie-Tooth disease are reported. Specifically, the p.I122N mutation was the cause of an intermediate form of Charcot-Marie-Tooth disease, and the p.K28I missense mutation predominately led to the demyelinating form. Functional studies demonstrated that the p.K28I variant significantly reduced expression of the protein, but the p.I122N variant increased. In addition, the p.I122N mutant protein exhibited the aggregation in neuroblastoma cell lines and the patient's peroneal nerve. Either gain-of-function or partial loss-of-function mutations to C1ORF194 can specify different causal mechanisms responsible for Charcot-Marie-Tooth disease with a wide range of clinical severity. Moreover, a knock-in mouse model confirmed that the C1orf194 missense mutation p.I121N led to impairments in motor and neuromuscular functions, and aberrant myelination and axonal phenotypes. The loss of normal C1ORF194 protein altered intracellular Ca2+ homeostasis and upregulated Ca2+ handling regulatory proteins. These findings describe a novel protein with vital functions in peripheral nervous systems and broaden the causes of Charcot-Marie-Tooth disease, which open new avenues for the diagnosis and treatment of related neuropathies.

Role of tissue-specific promoter DNA methylation in regulating the human EKLF gene.

Erythroid Krüppel-like factor (EKLF/KLF1) is an erythroid-specific transcription factor whose activity is essential for erythropoiesis. The underlying mechanisms for EKLF specifically restricted to erythroid cells are of great interest but remain incompletely understood. To explore the epigenetic regulation of EKLF expression by promoter DNA methylation, we investigated the methylation status of the EKLF promoter and EKLF gene expression from a panel of human tissues. We observed that erythroid-specific hypomethylation of the EKLF promoter in adult erythroid cells was positively associated with EKLF expression. Demethylation of the EKLF promoter by 5-aza-2'-deoxycytidine led to elevated EKLF expression in non-erythroid cells. We further uncovered that EKLF promoter DNA methylation reduced the binding affinity for the transcription factors GATA1 and c-myb (MYB), which in turn silenced EKLF expression. These results suggest that hypomethylation of the EKLF promoter has functional significance in the establishment and maintenance of erythroid-specific gene expression.

A Free Tetrazolyl Decorated Metal-Organic Framework Exhibiting High and Selective CO2 Adsorption.

In this work, we employed a new tetrazolyl-functionalized ligand, 5-(1H-tetrazole-5-yl)-1,3-bis(3,5-dicarboxylphenyl)-benzene (H5TBDPB), and successfully obtained an example of incorporating free tetrazolyl groups in transition-metal-based MOFs based upon an ideal MOF platform. With a BET surface area of 2070 m2 g-1, this new tetrazolyl-decorated MOF [Cu6(TBDPB)3(H2O)6]·9DMF·15H2O (HHU-5, HHU for Hohai University) exhibits a high CO2 adsorption capacity of 37.1 wt % at 1 bar and 273 K and high CO2 separation capacity toward N2 and CH4 as well.

Worm-Shape Pt Nanocrystals Grown on Nitrogen-Doped Low-Defect Graphene Sheets: Highly Efficient Electrocatalysts for Methanol Oxidation Reaction.

Although direct methanol fuel cell offers high energy use efficiency and low pollution emission, the lack of suitable electrode materials poses a great challenge to its commercial application. Herein, a facile and scalable approach is developed to fabricate a hybrid electrocatalyst consisting of strongly coupled worm-shape Pt nanocrystals and nitrogen-doped low-defect graphene (N-LDG) sheets. Interestingly, it is found that the formation of Pt nanoworms (NWs) is induced by the N atoms in the high-quality carbon matrix, which also allows the integration of their respective structural advantages and leads to a strong synergetic coupling effect. As a result, the obtained Pt NW/N-LDG catalyst exhibits an extremely high mass activity of 1283.1 mA mg-1 toward methanol oxidation reaction, accompanied by reliable long-term stability and good antipoisoning ability, which are dramatically enhanced as compared with conventional Pt nanoparticle catalysts dispersed on undoped LDG, reduced graphene oxide, and commercial carbon black supports.

Genetic diagnosis of polycystic kidney disease, Alport syndrome, and thalassemia minor in a large Chinese family.

Polycystic kidney disease (PKD) and Alport syndrome (AS) are serious inherited disorders associated with renal disease, and thalassemia is a hereditary blood disease with a high prevalence in south China. Here, we report an exceptional PKD coincidence of thalassemia minor and AS (diagnosed genetically) in a large Chinese family. Whole genome next-generation sequencing (NGS) was performed on the proband, and all family members underwent clinical evaluation. Sanger sequencing was used to validate the mutations distinguished by NGS. The pathogenic potential of the variants were evaluated by Polymorphism Phenotyping v2 (PolyPhen-2), Sorting Intolerant From Tolerant (SIFT) algorithm, and MutationTaster. Immunohistochemical, Western blot, immunofluorescent, and TdT-mediated dUTP nick-end labeling (TUNEL) analyses were performed to investigate polycystin 1 (PC1) expression, and cell proliferation and apoptosis in kidney tissues from the proband and normal control. A novel frameshift polycystic kidney disease 1 (PKD1) mutation (c.3903delC, p.A1302Pfs) was identified to be responsible for renal disease in this family. PC1 expression, and cell proliferation and apoptosis were significantly increased in the kidney tissues of the proband. Moreover, a deletion of approximately 19.3 kb of DNA with α-globin genes (_ _SEA) was associated with thalassemia minor in the family. In addition, a collagen type IV α 5 chain (COL4A5) variant (c.2858G>T, rs78972735), annotated as a pathogenic mutation in dbSNP and human gene mutation database (HGMD), was found in four family members with no clinical traits of AS. A novel pathogenic PKD1 mutation (c.3903delC) and (_ _SEA) thalassemia deletion were found to be responsible for the clinical symptoms in this family. The reported pathogenic COL4a5 variant (c.2858G>T, rs78972735) was not pathogenic alone.

A Double Heterozygous Mutation of TNNI3 Causes Hypertrophic Cardiomyopathy in a Han Chinese Family.

OBJECTIVES: To investigate the variations in the TNNI3 gene in a Chinese Han family affected by hypertrophic cardiomyopathy (HCM) and the potential molecular mechanism linking these mutations with disease. METHODS: Peripheral venous blood was acquired from family members, and TNNI3 mutations were identified by DNA sequencing. The pathophysiology of TNNI3 mutations was investigated using bioinformatics, subcellular localization determination and Western blotting. RESULTS: Sanger sequencing revealed that the proband possessed 2 heterozygous mutations, c.235C>T and c.470C>T, located at exons 4 and 6 of the TNNI3 gene. The proband (II-2) and her brother (II-1), who had been previously diagnosed with HCM, harbored both mutations whereas their healthy parents harbored only 1. Alignment of the TNNI3 amino acid sequence indicated that the two Pro residues were highly conserved across species. Subcellular localization showed that both wild-type (WT) and mutant TNNI3 proteins were localized at the cell nucleus. Western blot analysis of expression in human embryonic kidney 293T cells showed that the intracellular levels of the mutant proteins were significantly decreased compared to WT TNNI3 (p < 0.01). CONCLUSIONS: Our findings showed that a double heterozygous mutation in the TNNI3 gene is involved in the pathogenesis of HCM via haploinsufficiency. These results will inspire further studies to investigating the link between the TNNI3 gene and HCM.

Use of novel taurine-chitosan mediated liposomes for enhancing the oral absorption of doxorubicin via the TAUT transporter.

Our research aimed to enhance the oral bioavailability of doxorubicin hydrochloride (DOX·HCl) while minimizing the potential for myocardial toxicity. To achieve this goal, we developed a new method that utilizes a coating material to encapsulate the drug in liposomes, which can specifically target intestinal taurine transporter proteins. This coating material, TAU-CS, was created by combining taurine with chitosan. We characterized TAU-CS using various methods, including 1H NMR, FT-IR, and scanning electron microscopy (SEM). The resulting liposomes exhibited a regular spherical morphology, with a particle size of 195.7 nm, an encapsulation efficiency of 91.23 %, and a zeta potential of +11.65 mV. Under simulated gastrointestinal conditions, TAU-CS/LIP@DOX·HCl exhibited good stability and slow release. Pharmacokinetic studies revealed that, compared with DOX·HCl, TAU-CS/LIP@DOX·HCl had a relative bioavailability of 342 %. Intracellular uptake, immunofluorescence imaging, and permeation assays confirmed that the taurine transporter protein mediates the intestinal uptake of these liposomes. Our study suggested that liposomes coated with TAU-CS could serve as an effective oral delivery system and that targeting the taurine transporter protein shows promise in enhancing drug absorption.

Functional exosomes modified with chitosan effectively alleviate anthracycline-induced cardiotoxicity.

Anthracyclines belong to a class of anti-tumor antibiotics, and their severe cardiotoxicity significantly limits their clinical use. Exosomes play key roles in intercellular communication, characterized by high biocompatibility and specific tissue and organ homing effects. In this study, doxorubicin, an anthracycline anticancer drug widely used in clinical chemotherapy, was selected as a model drug. To address the significant cardiotoxicity associated with doxorubicin, tumor exosomes are utilized as drug carriers. The homing effect of autologous exosomes enhances drug uptake by tumor cells and reduces cardiotoxicity. To enhance the stability of exosomes, improve therapeutic effectiveness, and reduce toxic side effects, chitosan was utilized to modify the surface of exosomes. Chitosan has a specific anti-tumor effect because it can target the CD44 receptor of tumor stem cells and interact with tumor cells through charge adsorption. Through in vitro cell experiments, in vivo pharmacokinetic experiments, and an in situ ectopic nude mouse tumor model, the study demonstrated that chitosan-modified tumor exosomes significantly alleviated the severe cardiotoxicity of doxorubicin, while also showing remarkable anti-tumor efficacy. This study introduces a novel approach to reduce the adverse side effects of anthracycline chemotherapeutic drugs and presents a highly promising nanocarrier delivery system.

Highly sensitive "off-on" sensor based on MXene and magnetic microspheres for simultaneous detection of lung cancer biomarkers - Neuron specific enolase and carcinoembryonic antigen.

In this work, a highly sensitive lung cancer biomarkers detection probe was developed based on Ag and MXene co-functionalized magnetic microspheres. By using carboxyl magnetic microspheres as carrier, MXene was coated repeatedly by Poly (allylamine hydrochloride) (PAH) as interlayer adhesive, and silver particles grown on the surface of MXene in situ can efficiently improve the sensitivity of the probe. The detection of neuron specific enolase (NSE) is mainly through the formation of a specific complex between NSE antigen and antibody, and the release of antibody labeled with amino carbon quantum dots (CQDs) from the surface of Ag nanoparticles (AgNPs), so that the fluorescence is restored and "OFF-ON" is formed. The biosensor exhibits excellently wide linear range (0.0001-1500 ng/mL) and the limit of detection (LOD) is up to 0.03 pg/mL, which is superior to most tumor marker probes based on fluorescence mechanism. Furthermore, we constructed dual detection strategy for NSE and carcinoembryonic antigen (CEA) simultaneously.

Novel Polyurethane Based, Fully Flexible, High-Performance Piezoresistive Sensor for Real-Time Pressure Monitoring.

Flexible piezoresistive pressure sensors are garnering substantial attention, in line with advancements in biointegrated and wearable electronics. However, a significant portion of piezoresistive pressure sensors suffer from the trade-off between sensitivity and pressure range. Moreover, the current piezoresistive sensors generally rely on a rigid metallic electrode, severely deteriorating their long-term durability. Herein, a fully flexible piezoresistive sensor coupling polyurethane (PU) based electrode and active sensing element is proposed to circumvent the aforementioned problems. By rationally regulating the double-permeable conductive networks within the PU matrix, an elastomeric electrode and sensing element are implemented, respectively. The assembled heterostructured configurations enable impressive sensitivity up to 7.023 kPa-1, broad pressure detection (up to 420 kPa), an ultralow pressure sensing limit (0.1 Pa), and extraordinary operation stability over 80000 cyclic pressings along with fast response/relaxation times (60 ms/80 ms). Additionally, the fully flexible sensor is capable of both real-time detection of physiological signals and mimicking keyboards, implying its viability as a high-performance pressure sensor.

3-Methylthiophene: A Sustainable Solvent for High-Performance Organic Solar Cells.

The use of harmful halogenated or aromatic solvents such as chloroform (CF), chlorobenzene (CB), and o-xylene (o-XY) is one of the greatest barriers to the industrial-scale manufacturing of high-performance organic solar cells (OSCs). Therefore, it is necessary to eliminate the effects of these solvents to ensure practical feasibility of OSCs. We found that the anthracene-terminated polymer donor and small-molecule acceptor BO-4Cl had good solubility in 3-methylthiophene (3-MeT). There were no toxicity labels in the SDS and exposure control limits for 3-MeT. An overall power conversion efficiency of 16.87% was achieved by using 3-MeT as the solvent for solar cell fabrication, which was higher than that of the cells made from CF (16.18%) and o-XY (15.69%). The best OSC based on PM6:D18:L8-BO and fabricated with 3-MeT exhibited a high PCE of 18.13%, which is one of the highest values for cells fabricated from halogen-free solvents. These results indicate that 3-MeT is an eco-friendly and low-toxicity solvent for the sustainable fabrication of the OSC active layer.

Advancements in Noble Metal-Decorated Porous Carbon Nanoarchitectures: Key Catalysts for Direct Liquid Fuel Cells.

Noble-metal nanocrystals have emerged as essential electrode materials for catalytic oxidation of organic small molecule fuels in direct liquid fuel cells (DLFCs). However, for large-scale commercialization of DLFCs, adopting cost-effective techniques and optimizing their structures using advanced matrices are crucial. Notably, noble metal-decorated porous carbon nanoarchitectures exhibit exceptional electrocatalytic performances owing to their three-dimensional cross-linked porous networks, large accessible surface areas, homogeneous dispersion (of noble metals), reliable structural stability, and outstanding electrical conductivity. Consequently, they can be utilized to develop next-generation anode catalysts for DLFCs. Considering the recent expeditious advancements in this field, this comprehensive review provides an overview of the current progress in noble metal-decorated porous carbon nanoarchitectures. This paper meticulously outlines the associated synthetic strategies, precise microstructure regulation techniques, and their application in electrooxidation of small organic molecules. Furthermore, the review highlights the research challenges and future opportunities in this prospective research field, offering valuable insights for both researchers and industry experts.