Effect of Probiotic Supplementation on the Gut Microbiota Composition of Infants Delivered by Cesarean Section: An Exploratory, Randomized, Open-label, Parallel-controlled Trial.

BACKGROUND: Infants born via cesarean section (CS) are at an increased risk of immune-related diseases later in life, potentially due to altered gut microbiota. Recent research has focused on the administration of probiotics in the prevention of gut microbiota dysbiosis in neonates delivered by CS. This study was performed to investigate the effects of probiotic supplementation on the gut microbiota of CS-delivered infants. METHODS: Thirty full-term neonates delivered by CS were randomized into the intervention (supplemented orally with a probiotic containing Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis for 2 weeks) and control groups. Stool samples were collected at birth and 2 weeks and 42 days after birth. The composition of the gut microbiota was analyzed using 16S rRNA sequencing technology. RESULTS: The applied bacterial strains were abundant in the CS-delivered infants supplemented with probiotics. Probiotics increased the abundance of some beneficial bacteria, such as Bacteroides, Acinetobacter, Veillonella, and Faecalibacterium. Low colonization of Klebsiella, a potentially pathogenic bacterium, was observed in the intervention group. CONCLUSIONS: Our results showed that probiotics supplemented immediately after CS enriched the gut microbiota composition and altered the pattern of early gut colonization. TRIAL REGISTRATION: registration number NCT05086458.

DDX24 Is Essential for Cell Cycle Regulation in Vascular Smooth Muscle Cells During Vascular Development via Binding to FANCA mRNA.

BACKGROUND: The DEAD-box family is essential for tumorigenesis and embryogenesis. Previously, we linked the malfunction of DDX (DEAD-box RNA helicase)-24 to a special type of vascular malformation. Here, we aim to investigate the function of DDX24 in vascular smooth muscle cells (VSMCs) and embryonic vascular development. METHODS: Cardiomyocyte (CMC) and VSMC-specific Ddx24 knockout mice were generated by crossing Tagln-Cre mice with Ddx24flox/flox transgenic mice. The development of blood vessels was explored by stereomicroscope photography and immunofluorescence staining. Flow cytometry and cell proliferation assays were used to verify the regulation of DDX24 on the function of VSMCs. RNA sequencing and RNA immunoprecipitation coupled with quantitative real-time polymerase chain reaction were combined to investigate DDX24 downstream regulatory molecules. RNA pull-down and RNA stability experiments were performed to explore the regulation mechanism of DDX24. RESULTS: CMC/VSMC-specific Ddx24 knockout mice died before embryonic day 13.5 with defects in vessel formation and abnormal vascular remodeling in extraembryonic tissues. Ddx24 knockdown suppressed VSMC proliferation via cell cycle arrest, likely due to increased DNA damage. DDX24 protein bound to and stabilized the mRNA of FANCA (FA complementation group A) that responded to DNA damage. Consistent with the function of DDX24, depletion of FANCA also impacted cell cycle and DNA repair of VSMCs. Overexpression of FANCA was able to rescue the alterations caused by DDX24 deficiency. CONCLUSIONS: Our study unveiled a critical role of DDX24 in VSMC-mediated vascular development, highlighting a potential therapeutic target for VSMC-related pathological conditions.

IGFBP3 induced by the TGF-ß/EGFRvIII transactivation contributes to the malignant phenotype of glioblastoma.

Dual or multi-targets therapy targeting epidermal growth factor receptor variant III (EGFRvIII) and other molecular may relax the constraint for glioblastoma (GBM), putting forward the urgent requirement of finding candidate molecules. Here, the insulin-like growth factor binding protein-3 (IGFBP3) was considered a candidate, whereas the mechanisms of IGFBP3 production remain unclear. We treated GBM cells with exogenous transforming growth factor ß (TGF-ß) to simulate the microenvironment. We found that TGF-ß and EGFRvIII transactivation induced the activation of transcription factor c-Jun, which specifically bound to the promoter region of IGFBP3 through Smad2/3 and ERK1/2 pathways and promoted the production and secretion of IGFBP3. IGFBP3 knockdown inhibited the activation of TGF-ß and EGFRvIII signals and the malignant behaviors triggered by them in vitro and in vivo. Collectively, our results indicated a positive feedback loop of p-EGFRvIII/IGFBP3 under administration of TGF-ß, blocking IGFBP3 may be an additional target in EGFRvIII-expressing GBM-selective therapeutic strategy.

Antibiotic Changes Host Susceptibility to Eimeria falciformis Infection Associated with Alteration of Gut Microbiota.

Eimeria falciformis is a murine-infecting coccidium that mainly infects the cecum and colon where it coexists with a large number of endogenous bacteria. Here, we found that mice treated with a broad-spectrum antibiotic cocktail including ampicillin, neomycin, metronidazole, and vancomycin had less oocyst production and milder pathological consequences after E. falciformis infection than mice without antibiotics, regardless of the inoculation doses. Furthermore, we showed that antibiotic treatment reduced parasitic invasion and prolonged asexual stage during E. falciformis infection, which may result in alleviating the infection. Interestingly, when further defining different antibiotic combinations for E. falciformis infection, it was shown that mice treated with ampicillin plus vancomycin had substantially attenuated E. falciformis infections as measured by cecal parasite counts and histopathological features. In contrast, treatment with metronidazole plus neomycin was beneficial to E. falciformis infection. Analyses of gut microbiota revealed various changes in bacterial composition and diversity following antibiotic treatments that were associated with host susceptibility to E. falciformis infection. Together, these findings suggest that gut microbiota may regulate the course and pathogenicity of E. falciformis infection, while the mechanisms need to be further investigated, especially for the development of coccidial vaccines for use in farm animals.

The Jahn-Teller Effect for Amorphization of Molybdenum Trioxide towards High-Performance Fiber Supercapacitor.

Amorphous pseudocapacitive nanomaterials are highly desired in energy storage applications for their disordered crystal structures, fast electrochemical dynamics, and outstanding cyclic stability, yet hardly achievable using the state-of-the-art synthetic strategies. Herein, for the first time, high capacitive fiber electrodes embedded with nanosized amorphous molybdenum trioxide (A-MoO3-x) featuring an average particle diameter of ~20 nm and rich oxygen vacancies are obtained via a top-down method using α-MoO3 bulk belts as the precursors. The Jahn-Teller distortion in MoO6 octahedra due to the doubly degenerate ground state of Mo5+, which can be continuously strengthened by oxygen vacancies, triggers the phase transformation of α-MoO3 bulk belts (up to 30 µm long and 500 nm wide). The optimized fibrous electrode exhibits among the highest volumetric performance with a specific capacitance (C V ) of 921.5 F cm-3 under 0.3 A cm-3, endowing the fiber-based weaveable supercapacitor superior C V and E V (energy density) of 107.0 F cm-3 and 9.5 mWh cm-3, respectively, together with excellent cyclic stability, mechanical robustness, and rate capability. This work demonstrates a promising strategy for synthesizing nanosized amorphous materials in a scalable, cost-effective, and controllable manner.

Mechanistic insight in site-selective and anisotropic etching of prussian blue analogues toward designable complex architectures for efficient energy storage.

Engineering coordination compounds, e.g., prussian blue (PB) and its analogues (PBAs), with designable complex nanostructures via chemical etching holds great opportunities for improving energy storage performances by adjusting topological geometry, selectively exposing active sites, tuning electronic properties and enhancing accessible surface area. Unfortunately, it remains ambiguous particularly on site-selective and anisotropic etching behaviors. Herein, for the first time, we propose that two distinct regions are formed inside NiCo PBA (NCP) cubes due to the competition between classical ion-by-ion crystallization and non-classical crystallization based on aggregation. Such a unique structure ultimately determines not only the etching position but also the anisotropic pathway by selectively exposing unprotected Ni sites. According to this principle, complex PBA architectures, including nanocages, open nanocubes (constructed by six cones sharing the same apex), nanocones, and chamfer nanocubes can be intentionally obtained. After thermal annealing, NCP nanocones are converted to morning glory-like porous architectures composed of NiO/NiCo2O4 heterostructures with a mean particle size of 5 nm, which show improved rate performance and cycling stability.

Solution-Processed Sensing Textiles with Adjustable Sensitivity and Linear Detection Range Enabled by Twisting Structure.

Wearable strain sensors are emerging rapidly for their promising applications in human motion detection for diagnosis, healthcare, training instruction, and rehabilitation exercise assessment. However, it remains a bottleneck in gaining comfortable and breathable devices with the features of high sensitivity, linear response, and tunable detection range. Textiles possess fascinating advantages of good breathability, aesthetic property, tailorability, and excellent mechanical compliance to conformably attach to human body. As the meandering loops in a textile can be extended in different directions, it provides plenty of room for exploring ideal sensors by tuning a twisting structure with rationally selected yarn materials. Herein, textile sensors with twisting architecture are designed via a solution-based process by using a stable water-based conductive ink that is composed of polypyrrole/polyvinyl alcohol nanoparticles with a mean diameter of 50 nm. Depending on the predesigned twisting models, the thus-fabricated textile sensors show adjustable performances, exhibiting a high sensitivity of 38.9 with good linearity and a broad detection range of 200%. Such sensors can be integrated into fabrics and conformably attached to skin for monitoring subtle (facial expressions, breathing, and speaking) and large (stretching, jumping, running and jogging, and sign language) human motions. As a proof-of-concept application, by integrating with a wireless transmitter, the signals detected by our sensors during exercise (e.g., running) can be remotely received and displayed on a smartphone. It is believed that the integration of our textile sensors with selected twisting models into a cloth promises full-range motion detection for wearable electronics and human-machine interfaces.

Polarity-assisted formation of hollow-frame sheathed nitrogen-doped nanofibrous carbon for supercapacitors.

Heteroatom-doped carbon nanostructures with uniform size and morphology, well-designed architectures, and minimized interfacial resistance have been recognized as promising electrode materials for energy storage, but remain a crucial challenge. Herein, we develop a general approach of polarity-induced decoration of a monolayer sheath of metal-organic framework (MOF) particles with excellent uniformity in size and morphology on electrospun polymer nanofibers. These hybrid nanofibers are facilely converted into nitrogen-doped nanofibrous carbon (denoted as N-NFC) during pyrolysis. The thus-obtained N-NFC features (1) a one-dimensional nanofibrous structure with a highly conductive core, (2) a monolayer sheath of hollow carbon-frames with uniform size and morphology, (3) plenty of micro/mesopores with a highly accessible surface area, and (4) a high N-doping level, all of which guarantee its good electrochemical performance with a high capacitance of 387.3 F g-1 at 1 A g-1. In a solid-state supercapacitor, it delivers excellent rate capability (78.0 F g-1 at 0.2 A g-1 and 64.0 F g-1 at 1 A g-1), an enhanced energy density of 7.9 W h kg-1 at a power density of 219 W kg-1, and outstanding cycling stability with 90% capacity retained over 10 000 cycles at 1 A g-1.

Oxygen vacancy enriched hollow cobaltosic oxide frames with ultrathin walls for efficient energy storage and biosensing.

Transition metal oxides (TMOs) with desired morphologies and atomic structures have promising applications in energy storage, catalysis, and biosensing because of their large specific surface area, high theoretical capacitance, abundant active sites, etc. In this study, hierarchical Co3O4 with enriched oxygen vacancies and finely tuned nanostructures, e.g. high porosity, thin wall thickness, hollow or yolk-shell structure, is prepared by dynamically balancing the decomposition and oxidation of the zeolitic imidazolate framework-67 (ZIF-67) precursor directly calcined in air at 300 °C. The optimized Co3O4 hollow frame inherits the original shape of the parent ZIF-67 with a high volume retention of 83% and features an ultrathin wall thickness of 10 nm, a large accessible surface area of 63.7 m2 g-1 and a high content of surface oxygen vacancies. It thus delivers an excellent specific capacitance of 770 F g-1 at 1 A g-1, a rate capability of 570.9 F g-1 at 20 A g-1 and excellent cycling stability for energy storage, and a high sensitivity of 0.7 mA mM-1 cm-2, a low detection limit of 0.2 µM (S/N = 3), and a wide linear detectable range of 0.005-1.175 mM for electrochemical non-enzymatic detection of glucose.

A Solid-State Fibriform Supercapacitor Boosted by Host-Guest Hybridization between the Carbon Nanotube Scaffold and MXene Nanosheets.

Fiber-shaped supercapacitors with improved specific capacitance and high rate capability are a promising candidate as power supply for smart textiles. However, the synergistic interaction between conductive filaments and active nanomaterials remains a crucial challenge, especially when hydrothermal or electrochemical deposition is used to produce a core (fiber)-shell (active materials) fibrous structure. On the other hand, although 2D pseudocapacitive materials, e.g., Ti3 C2 T x (MXene), have demonstrated high volumetric capacitance, high electrical conductivity, and hydrophilic characteristics, MXene-based electrodes normally suffer from poor rate capability owing to the sheet restacking especially when the loading level is high and solid-state gel is used as electrolyte. Herein, by hosting MXene nanosheets (Ti3 C2 T x ) in the corridor of a scrolled carbon nanotube (CNT) scaffold, a MXene/CNT fiber with helical structure is successfully fabricated. These features offer open spaces for rapid ion diffusion and guarantee fast electron transport. The solid-state supercapacitor based on such hybrid fibers with gel electrolyte coating exhibits a volumetric capacitance of 22.7 F cm-3 at 0.1 A cm-3 with capacitance retention of 84% at current density of 1.0 A cm-3 (19.1 F cm-3 ), improved volumetric energy density of 2.55 mWh cm-3 at the power density of 45.9 mW cm-3 , and excellent mechanical robustness.

Up-regulation of MSH6 is associated with temozolomide resistance in human glioblastoma.

The impact of DNA mismatch repair (MMR) on resistance to temozolomide (TMZ) therapy in patients with glioblastoma (GBM) is recently reported but the mechanisms are not understood. We aim to analyze the correlation between MMR function and the acquired TMZ resistance in GBM using both relevant clinical samples and TMZ resistant cells. First we found increased expression of MSH6, one of key components of MMR, in recurrent GBM patients' samples who underwent TMZ chemotherapy, comparing with those matched samples collected at the time of diagnosis. Using the cellular models of acquired resistance to TMZ, we further confirmed the up-regulation of MSH6 in TMZ resistant cells. Moreover, a TCGA dataset contains a large cohort of GBM clinical samples with or without TMZ treatment reinforced the increased expression of MSH6 and other MMR genes after long-term TMZ chemotherapy, which may resulted in MMR dysfunction and acquired TMZ resistance. Our results suggest that increased expression of MSH6, or other MMR, may be a new mechanism contributing to the acquired resistance during TMZ therapy; and may serve as an indicator to the resistance in GBM.

Design of a wearable and shape-memory fibriform sensor for the detection of multimodal deformation.

A wearable and shape-memory strain sensor with a coaxial configuration is designed, comprising a thermoplastic polyurethane fiber as the core support, well-aligned and interconnected carbon nanotubes (CNTs) as conductive filaments, and polypyrrole (PPy) coating as the cladding layer. In this design, the stress relaxation between CNTs is well confined by the outer PPy cladding layer, which endows the fibriform sensor with good reliability and repeatability. The microcracks generated when the coaxial fiber is under strain guarantee the superior sensitivity of this fibriform sensor with a gauge factor of 12 at 0.1% strain, a wide detectable range (from 0.1% to 50% tensile strain), and the ability to detect multimodal deformation (tension, bending, and torsion) and human motions (finger bending, breathing, and phonation). In addition, due to its shape-memory characteristic, the sensing performance of the fibriform sensor is well retained after its shape recovers from 50% deformation and the fabric woven from the shape-memory coaxial fibers can be worn on the elbow joints in a reversible manner (original-enlarged-recovered) and fitted tightly. Thus, this sensor shows promising applications in wearable electronics.

General Metal-Ion Mediated Method for Functionalization of Graphene Fiber.

Graphene fibers (GFs) are attractive materials for wearable electronics because of their lightness, superior flexibility, and electrical conductivity. However, the hydrophobic nature and highly stacked structure endow GFs similar characteristics in nature to solid carbon fibers. Therefore, the interior functionalization of GFs so as to achieve synergistic interaction between graphene nanosheets and active materials thus enhance the performance of hybrid fibers remains a challenge. Herein, a general metal-ion mediated strategy is developed to functionalize GFs and nanoparticles of Cu, Fe2O3, NiO, and CoO are successfully incorporated into GFs, respectively. As proof-of-concept applications, the obtained functionalized GFs are used as electrodes for electrochemical sensors and supercapacitors. The performances of thus-devised fiber sensor and supercapacitor are greatly improved.

Highly Concentrated, Ultrathin Nickel Hydroxide Nanosheet Ink for Wearable Energy Storage Devices.

Solution-based techniques are considered as a promising strategy for scalable fabrication of flexible electronics owing to their low-cost and high processing speed. The key to the success of these techniques is dominated by the ink formulation of active nanomaterials. This work successfully prepares a highly concentrated two dimensional (2D) crystal ink comprised of ultrathin nickel hydroxide (Ni(OH)2 ) nanosheets with an average lateral size of 34 nm. The maximum concentration of Ni(OH)2 nanosheets in water without adding any additives reaches as high as 50 mg mL-1 , which can be printed on arbitrary substrates to form Ni(OH)2 thin films. As a proof-of-concept application, Ni(OH)2 nanosheet ink is coated on commercialized carbon fiber yarns to fabricate wearable energy storage devices. The thus-fabricated hybrid supercapacitors exhibit excellent flexibility with a capacitance retention of 96% after 5000 bending-unbending cycles, and good weavability with a high volumetric capacitance of 36.3 F cm-3 at a current density of 0.4 A cm-3 , and an energy density of 11.3 mWh cm-3 at a power density of 0.3 W cm-3 . As a demonstration of practical application, a red light emitting diode can be lighted up by three hybrid devices connected in series.