Nanofiber-induced hierarchically-porous magnesium phosphate bone cements accelerate bone regeneration by inhibiting Notch signaling.

Magnesium phosphate bone cements (MPC) have been recognized as a viable alternative for bone defect repair due to their high mechanical strength and biodegradability. However, their poor porosity and permeability limit osteogenic cell ingrowth and vascularization, which is critical for bone regeneration. In the current study, we constructed a novel hierarchically-porous magnesium phosphate bone cement by incorporating extracellular matrix (ECM)-mimicking electrospun silk fibroin (SF) nanofibers. The SF-embedded MPC (SM) exhibited a heterogeneous and hierarchical structure, which effectively facilitated the rapid infiltration of oxygen and nutrients as well as cell ingrowth. Besides, the SF fibers improved the mechanical properties of MPC and neutralized the highly alkaline environment caused by excess magnesium oxide. Bone marrow stem cells (BMSCs) adhered excellently on SM, as illustrated by formation of more pseudopodia. CCK8 assay showed that SM promoted early proliferation of BMSCs. Our study also verified that SM increased the expression of OPN, RUNX2 and BMP2, suggesting enhanced osteogenic differentiation of BMSCs. We screened for osteogenesis-related pathways, including FAK signaing, Wnt signaling and Notch signaling, and found that SM aided in the process of bone regeneration by suppressing the Notch signaling pathway, proved by the downregulation of NICD1, Hes1 and Hey2. In addition, using a bone defect model of rat calvaria, the study revealed that SM exhibited enhanced osteogenesis, bone ingrowth and vascularization compared with MPC alone. No adverse effect was found after implantation of SM in vivo. Overall, our novel SM exhibited promising prospects for the treatment of critical-sized bone defects.

A Universal Biomacromolecule-Enabled Assembly Strategy for Constructing Multifunctional Aerogels with 90% Inorganic Mass Loading from Inert Nano-Building Blocks.

Inert inorganic nano-building blocks, such as carbon nanotubes (CNTs) and boron nitride (BN) nanosheets, possess excellent physicochemical properties. However, it remains challenging to build aerogels with these inert nanomaterials unless they are chemically modified or compounded with petrochemical polymers, which affects their intrinsic properties and is usually not environmentally friendly. Here, a universal biomacromolecule-enabled assembly strategy is proposed to construct aerogels with 90 wt% ultrahigh inorganic loading. The super-high inorganic content is beneficial for exploiting the inherent properties of inert nanomaterials in multifunctional applications. Taking chitosan-CNTs aerogel as a proof-of-concept demonstration, it delivers sensitive pressure response as a pressure sensor, an ultrahigh sunlight absorption (94.5%) raising temperature under light (from 25 to 71 °C within 1 min) for clean-up of crude oil spills, and superior electromagnetic interference shielding performance of up to 68.9 dB. This strategy paves the way for the multifunctional application of inert nanomaterials by constructing aerogels with ultrahigh inorganic loading.

Precision medicine in colorectal cancer: Leveraging multi-omics, spatial omics, and artificial intelligence.

Colorectal cancer (CRC) is a leading cause of cancer-related deaths. Recent advancements in genomic technologies and analytical approaches have revolutionized CRC research, enabling precision medicine. This review highlights the integration of multi-omics, spatial omics, and artificial intelligence (AI) in advancing precision medicine for CRC. Multi-omics approaches have uncovered molecular mechanisms driving CRC progression, while spatial omics have provided insights into the spatial heterogeneity of gene expression in CRC tissues. AI techniques have been utilized to analyze complex datasets, identify new treatment targets, and enhance diagnosis and prognosis. Despite the tumor's heterogeneity and genetic and epigenetic complexity, the fusion of multi-omics, spatial omics, and AI shows the potential to overcome these challenges and advance precision medicine in CRC. The future lies in integrating these technologies to provide deeper insights and enable personalized therapies for CRC patients.

Janus silk fibroin/polycaprolactone-based scaffold with directionally aligned fibers and porous structure for bone regeneration.

To promote bone repair, it is desirable to develop three-dimensional multifunctional fiber scaffolds. The densely stacked and tightly arranged conventional two-dimensional electrospun fibers hinder cell penetration into the scaffold. Most of the existing three-dimensional structural materials are isotropic and monofunctional. In this research, a Janus nanofibrous scaffold based on silk fibroin/polycaprolactone (SF/PCL) was fabricated. SF-encapsulated SeNPs demonstrated stability and resistance to aggregation. The outside layer (SF/PCL/Se) of the Janus nanofiber scaffold displayed a structured arrangement of fibers, facilitating cell growth guidance and impeding cell invasion. The inside layer (SF/PCL/HA) featured a porous structure fostering cell adhesion. The Janus fiber scaffold containing SeNPs notably suppressed S. aureus and E. coli activities, correlating with SeNPs concentration. In vitro, findings indicated considerable enhancement in alkaline phosphatase (ALP) activity of MC3T3-E1 osteoblasts and upregulation of genes linked to osteogenic differentiation with exposure to the SF/PCL/HA/Se Janus nanofibrous scaffold. Moreover, in vivo, experiments demonstrated successful critical bone defect repair in mouse skulls using the SF/PCL/HA/Se Janus nanofiber scaffold. These findings highlight the potential of the SF/PCL-based Janus nanofibrous scaffold, integrating SeNPs and nHA, as a promising biomaterial in bone tissue engineering.

PXMP4 promotes gastric cancer cell epithelial-mesenchymal transition via the PI3K/AKT signaling pathway.

BACKGROUND: Peroxisomal membrane protein 4 (PXMP4), a member of the peroxisome membrane protein PXMP2/4 family, participates in the progression of several malignant cancers. Nevertheless, the effect of PXMP4 in the development of gastric cancer (GC) is still unknown. As a result, the focus of this investigation was to elucidate the potential mechanisms of PXMP4 in GC. METHODS AND RESULTS: Firstly, bioinformatics analysis results showed higher expression of PXMP4 in GC tissues. Secondly, clinical analysis of 57 patients with GC revealed correlations between PXMP4 expression and differentiation, depth of invasion, as well as TNM stage. Furthermore, individuals with elevated PXMP4 expression in GC exhibited an unfavorable prognosis. In vitro data showed the involvement of knockdown/overexpression of PXMP4 in the proliferation, invasion, and migration of GC cells, and triggering the epithelial-mesenchymal transition (EMT) of GC cells through the activation of the PI3K/AKT signaling pathway. LY294002, a PI3K/AKT inhibitor, inhibited the expression of PI3K/AKT-related proteins but did not affect the expression of PXMP4. CONCLUSIONS: These findings indicate that PXMP4 potentially functions as an upstream molecule in the PI3K/AKT pathway, governing the EMT process in GC.

Cellulose nanofibers embedded chitosan/tannin hydrogel with high antibacterial activity and hemostatic ability for drug-resistant bacterial infected wound healing.

Millions of patients annually suffer life-threatening illnesses caused by bacterial infections of skin wounds. However, the treatment of wounds infected with bacteria is a thorny issue in clinical medicine, especially with drug-resistant bacteria infections. Therefore, there is an increasing interest in developing wound dressings that can efficiently fight against drug-resistant bacterial infections and promote wound healing. In this work, an anti-drug-resistant bacterial chitosan/cellulose nanofiber/tannic acid (CS/CNF/TA) hydrogel with excellent wound management ability was developed by electrospinning and fiber breakage-recombination. The hydrogel exhibited an outstanding antibacterial property exceeding 99.9 %, even for drug-resistant bacteria. This hydrogel could adhere to the tissue surface due to its abundant catechol groups, which avoided the shedding of hydrogel during the movement. Besides, it exhibited extraordinary hemostatic ability during the bleeding phase of the wound and then regulated the wound microenvironment by absorbing water and moisturizing. Moreover, the CS/CNF/TA also promoted the regrowth of vessels and follicles, accelerating the healing of infected wound tissue, with a healing rate exceeding 95 % within a 14-day timeframe. Therefore, the CS/CNF/TA hydrogel opens a new approach for the healing of drug-resistant bacterial infected wounds.

Silk fibroin-chitosan aerogel reinforced by nanofibers for enhanced osteogenic differentiation in MC3T3-E1 cells.

Proper bone scaffolds should be biocompatible, mechanically robust and porous for cell migration. Here, pure silk fibroin (SF)- chitosan (CS) aerogel scaffolds reinforced with different amount of SF nanofibers (SF-CS/NF1%, SF-CS/NF2% and SF-CS/NF3%) are prepared for bone regeneration. Surface morphology and composition were analyzed to ensure successful integration of each component. Incorporating 3 % nanofibers endowed the aerogels with a resistance to 3.5 times the compressive stress of the pure SF-CS aerogels. The benefits of nanofibers were also confirmed by the high porosity of 72.3 ± 1.3 %, the regulated pore size and the high-water uptake ratio of 1770.4 ± 156.8 %. Enhanced cell viability of the aerogel scaffolds was verified with Cell Counting Kit-8 (CCK-8) assays, and confocal microscopy and scanning electron microscopy (SEM) images were taken to assess the cell migration and distribution. The cell differentiation on the aerogel scaffolds was evaluated with enzyme-linked immunosorbent assay (ELISA). Significantly higher level of Collagen type I (Col-I), osteocalcin (OCN), osteopontin (OPN), and alkaline phosphatase (ALP) expression was observed on SF-CS/NF3% aerogels. This biocompatible nanofiber-reinforced aerogel scaffold facilitates osteogenic differentiation by rougher surface, enhanced mechanical strength and well-regulated pores. Thus, as-prepared scaffolds may be further applied in bone regeneration field.

Janus Fibrous Mats Based Suspended Type Evaporator for Salt Resistant Solar Desalination and Salt Recovery.

Solar desalination has been recognized as an emerging strategy for solving the pressing global freshwater crisis. However, salt crystallization at the photothermal interface frequently causes evaporator failure. In addition, arbitrary discharge of concentrated brine produced during desalination results in potential ecological impacts as well as wastage of valuable minerals. In the present work, a suspended-type evaporator (STEs) constructed using Janus fibrous mats is reported. The fibrous structure wicks brine to the evaporation layer and the salt gets confined in the evaporation layer until crystallization for zero liquid discharge due to the suspended design. Enhanced evaporation is observed because STEs have an additional low-resistance vapor escape path directly from the evaporation layer to the atmosphere compared to traditional floating Janus evaporators. Moreover, owing to the drastically different wettability on both sides, the evaporator allows salt crystallization only on the hydrophilic bottom layer, thus eliminating salt accumulation at the hydrophobic photothermal interface. With this unique structural design, the proposed evaporator not only maintains a high evaporation rate of 1.94 kg m-2 h-1 , but also demonstrates zero liquid discharged salt resistance and ideal recovery of the mineral in brine.

Fabrication of PCD Skiving Cutter by UV Nanosecond Laser.

Polycrystalline diamond (PCD) skiving cutter has dominated research in recent years. However, the traditional methods of fabrication have failed to cut the diamond with high quality. We propose the two-step laser machining process combining roughing machining with orthogonal irradiation and finishing machining with tangential irradiation. In addition, the processing effect and mechanism of different lasers on the diamond were investigated by a finite element analysis. It's proved that the ultraviolet nanosecond laser is an excellent machining method for the processing of diamond. Furthermore, the effect of the processing parameters on the contour accuracy (Rt) was studied. The result indicates that the Rt value decreases first and then increases as the increase of the line interval, scanning speed and defocusing amount (no matter positive or negative defocus). Further, Raman spectroscopy was applied to characterize the diamond surface under different cutting methods and the flank face of the tool after processing. Finally, a high-quality PCD skiving cutter was obtained with an Rt of 5.6 µm and no phase transition damage.

Reed Leaves Inspired Silica Nanofibrous Aerogels with Parallel-Arranged Vessels for Salt-Resistant Solar Desalination.

Sufficient and clean freshwater is still out of reach for billions of people around the world. Solar desalination from brine is regarded as one of the most promising proposals to solve this severe crisis. However, most of the reported evaporators to date still suffer from the decreasing evaporation rate caused by salt crystallization accumulated on their surface. Here, inspired by the vascular tissue structure, transpiration, and antifouling function of reed leaves, we design biomimetic hierarchical nanofibrous aerogels with parallel-arranged vessels and hydrophobic surfaces for highly efficient and salt-resistant solar desalination. Foldable vessel walls and flexible silica nanofibers give the reed leaf-inspired nanofiber aerogels (R-NFAs) excellent mechanical properties and enable them to withstand repeated compression. Besides, the R-NFAs can efficiently absorb sunlight (light absorption efficiency: 94.8%) and evaporate the brine to vapor, similar to reed leaves (evaporation rate: 1.25 kg m-2 h-1 under 1 sun). More importantly, enabled by the hydrophobic surfaces and parallel-arranged vessels, the R-NFAs can work stably in high-concentration brine (saturated, 26.3 wt %) under high-intensity light (up to 6 sun), demonstrating potent salt resistance. It is expected that R-NFAs with combined antisalt pore and surface structures will provide a designed concept for salt-resistant solar desalination.

Identification of 22 novel BTK gene variants in B cell deficiency with hypogammaglobulinemia.

X-linked agammaglobulinemia (XLA) is an inborn error of immunity caused by pathogenic variants in the BTK gene, resulting in impaired B cell differentiation and maturation. Over 900 variants have already been described in this gene, however, new pathogenic variants continue to be identified. In this report, we describe 22 novel variants in BTK, associated with B cell deficiency with hypo- or agammaglobulinemia in male patients or in asymptomatic female carriers. Genetic data was correlated with BTK protein expression by flow cytometry, and clinical and family history to obtain a comprehensive assessment of the clinico-pathologic significance of these new variants in the BTK gene. For one novel missense variant, p.Cys502Tyr, site-directed mutagenesis was performed to determine the impact of the sequence change on protein expression and stability. Genetic data should be correlated with protein and/or clinical and immunological data, whenever possible, to determine the clinical significance of the gene sequence alteration.

Biomimetic Silk Fibroin Hydrogels Strengthened by Silica Nanoparticles Distributed Nanofibers Facilitate Bone Repair.

Various materials are utilized as artificial substitutes for bone repair. In this study, a silk fibroin (SF) hydrogel reinforced by short silica nanoparticles (SiNPs)-distributed-silk fibroin nanofibers (SiNPs@NFs), which exhibits a superior osteoinductive property, is fabricated for treating bone defects. SF acts as the base part of the composite scaffold to mimic the extracellular matrix (ECM), which is the organic component of a native bone. The distribution of SiNPs clusters within the composite hydrogel partially mimics the distribution of mineral crystals within the ECM. Incorporation of SiNPs@NFs enhances the mechanical properties of the composite hydrogel. In addition, the composite hydrogel provides a biocompatible microenvironment for cell adhesion, proliferation, and osteogenic differentiation in vitro. In vivo studies confirm that the successful repair is achieved with the formation of a large amount of new bone in the large-sized cranial defects that are treated with the composite hydrogel. In conclusion, the SiNPs@NFs-reinforced-hydrogel fabricated in this study has the potential for use in bone tissue engineering.

MXene-Graphene Field-Effect Transistor Sensing of Influenza Virus and SARS-CoV-2.

An MXene-graphene field-effect transistor (FET) sensor for both influenza virus and 2019-nCoV sensing was developed and characterized. The developed sensor combines the high chemical sensitivity of MXene and the continuity of large-area high-quality graphene to form an ultra-sensitive virus-sensing transduction material (VSTM). Through polymer linking, we are able to utilize antibody-antigen binding to achieve electrochemical signal transduction when viruses are deposited onto the VSTM surface. The MXene-graphene VSTM was integrated into a microfluidic channel that can directly receive viruses in solution. The developed sensor was tested with various concentrations of antigens from two viruses: inactivated influenza A (H1N1) HA virus ranging from 125 to 250,000 copies/mL and a recombinant 2019-nCoV spike protein ranging from 1 fg/mL to 10 pg/mL. The average response time was about ∼50 ms, which is significantly faster than the existing real-time reverse transcription-polymerase chain reaction method (>3 h). The low limit of detection (125 copies/mL for the influenza virus and 1 fg/mL for the recombinant 2019-nCoV spike protein) has demonstrated the sensitivity of the MXene-graphene VSTM on the FET platform to virus sensing. Especially, the high signal-to-viral load ratio (∼10% change in source-drain current and gate voltage) also demonstrates the ultra-sensitivity of the developed MXene-graphene FET sensor. In addition, the specificity of the sensor was also demonstrated by depositing the inactivated influenza A (H1N1) HA virus and the recombinant 2019-nCoV spike protein onto microfluidic channels with opposite antibodies, producing signal differences that are about 10 times lower. Thus, we have successfully fabricated a relatively low-cost, ultrasensitive, fast-responding, and specific inactivated influenza A (H1N1) and 2019-nCoV sensor with the MXene-graphene VSTM.

Advanced mechanism of multiphysics fields tip enhancement induced with varied laser power to fabricate pattern-transformable subdiffraction limit nanostructures.

The nanofabrication platform was carried out using an atomic force microscope (AFM) system and a continuous wave (cw) laser to investigate the influence of laser power on the underlying mechanism of nanostructures fabricated by multiphysics fields tip enhancement (MFTE) induced by a cw laser irradiating the AFM probe tip. The nanostructure fabrication of nanopits and grooves and nanodots and lines on a polymethyl methacrylate thin film was conducted in an ambient environment by changing the incident laser power. The dependence of the MFTE on laser power was numerically analyzed, too. The lateral dimensions of nanopits and grooves and nanodots and lines characterized in situ were 154 nm, 96 nm, 188 nm, and 25 nm, respectively, breaking the optical diffraction limit. It turned out that the nanostructures converted from craters (pits and grooves) to protrusions (dots and lines) when altered with the laser power. Different laser powers can trigger the MFTE to change, thus, inducing varied coupling energy, which is the essential mechanism for nanostructure conversion. We also established a model to analyze the nanostructures transition and to predict the dimensions of nanostructures. The simulation results demonstrate that the MFTE has an essential effect on the formation of nanostructures, which are in good agreement with the experimental results.

Direct 3D Printing of Silica Doped Transparent Magnesium Aluminate Spinel Ceramics.

Transparent magnesium aluminate spinel ceramics were additively manufactured via a laser direct deposition method in this study. With a minimum porosity of 0.3% achieved, highly transparent spinel samples with the highest total optical transmittance of 82% at a wavelength of 632.8 nm, were obtained by a 3D printing approach. However, cracking was found to be a major issue affecting printed spinel samples. To control prevalent cracking, the effect of silica dopants was investigated. Increased silica dopants reduced average total crack length by up to 79% and average crack density by up to 71%. However, a high dopant level limited optical transmission, attributed to increased porosity and formation of secondary phase. Further investigation found that with decreased average fracture toughness, from 2.4 MPa·m1/2 to 1.9 MPa·m1/2, the obvious reduction in crack formation after doping was related to decreased grain size and introduction of softer secondary phase during deposition. The study demonstrated the feasibility of the proposed laser direct deposition method in directly fabricating transparent spinel ceramics while dopants showed potentials in addressing cracking issues.

Cellular Structured CNTs@SiO2 Nanofibrous Aerogels with Vertically Aligned Vessels for Salt-Resistant Solar Desalination.

The emerging solar desalination technology is considered as one of the most promising strategies to ensure water security. However, with the proceeding of solar desalination, salt crystallization on the surface of solar evaporators caused by increasing salinity of seawater will result in a decrease in the evaporation rate. Thus, it is still challenging to fabricate solar evaporators with superior salt resistance. In this work, elastic ceramic-based nanofibrous aerogels with a cellular architecture are fabricated by the combination of electrospinning and fiber freeze-shaping technologies, which are composed of vertically aligned vessels and porous vessel walls. Under the action of convection and diffusion promoted by this unique cellular architecture, the aerogels exhibit a superior salt-resistance without any salt crystals on the surface of aerogels even in 20% brine and under 6-sun irradiation. Moreover, by virtue of the synergistic effect of the promising structure and light absorbance of carbon nanotubes, aerogels possess a high light absorbance of up to 98% and excellent evaporation performance achieving 1.50 kg m-2 h-1 under 1-sun irradiation. This work may provide a fascinating avenue for the desalination of seawater in a salt-resistance and efficient manner.

Red Fluorescent Carbon Dot Powder for Accurate Latent Fingerprint Identification using an Artificial Intelligence Program.

Development and comparison of the latent fingerprints (LFPs) are two major studies in detection and identification of LFPs, respectively. However, integrated research studies on both fluorescent materials for LFP development and digital-processing programs for LFP comparison are scarcely seen in the literature. In this work, highly efficient red-emissive carbon dots (R-CDs) are synthesized in one pot and mixed with starch to form R-CDs/starch phosphors. Such phosphors are comparable with various substrates and suitable for the typical powder dusting method to develop LFPs. The fluorescence images of the developed LFPs are handled with an artificial intelligence program. For the optimal sample, this program presents an excellent matching score of 93%, indicating that the developed sample has very high similarity with the standard control. Our results are significantly better than the benchmark obtained by the traditional method, and thus, both the R-CDs/starch phosphors and the digital processing program fit well for the practical applications.

Effect of video-assisted thoracoscopic surgery on pain stress indicators NO, IL-1ß and IL-6 in the treatment of mediastinal tumor in children.

This study aimed to investigate the effect of video-assisted thoracoscopic surgery (VATS) on pain stress indicators nitric oxide (NO), interleukin-1ß (IL-1ß) and IL-6 in the treatment of mediastinal tumor in children, so as to explore the clinical application value of this surgery. A retrospective analysis was performed on 82 children with mediastinal tumor undergoing operation in Children's Hospital Affiliated to Zhengzhou University from January 2012 to January 2016. Among them, 48 children undergoing VATS were enrolled as an observation group, and 34 children undergoing conventional thoracotomy were enrolled as a control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the preoperative and postoperative expression levels of NO, IL-1ß and IL-6. The intraoperative clinical data, postoperative pain degree and infection rate were observed and recorded in real time, and then compared between the two groups. Before operation (T0), there were no statistically significant differences between the two groups in serum NO, IL-1ß and IL-6 expression levels, which were lower in the observation group than those in the control group at 12 h (T1) and 24 h (T2) after operation (P<0.05). The visual analog scale (VAS) score in the observation group was lower than that in the control group at T1 (P<0.05). Compared with the control group, the largest blade opening, intraoperative blood loss, drainage duration and postoperative pain degree were significantly improved in the observation group. The postoperative infection rate was 4.17% in the observation group, significantly lower than 17.64% in the control group. VATS is effective for postoperative pain stress indicators and infection control in children with mediastinal tumor, which is therefore more suitable for children with the disease and has a higher clinical value.

Highly flexible, mesoporous structured, and metallic Cu-doped C/SiO2 nanofibrous membranes for efficient catalytic oxidative elimination of antibiotic pollutants.

The development of inorganic membranous catalysts with both large mesopores and superb flexibility is extremely favorable for the enhancement of their catalytic oxidation activity for the degradation of antibiotic pollutants in wastewater via sulfate radical-based advanced oxidation processes; however, there still exists a huge challenge for inorganic materials to simultaneously realize these two properties. Herein, metallic copper-doped carbon/silica nanofibrous membranes (Cu@C/SiO2 NFMs) with large mesopores, superb flexibility, and robust mechanical strength were fabricated through a sol-gel electrospinning and subsequent in situ carbonization reduction method. The synthesized Cu nanoparticles were homogeneously distributed throughout the mesoporous C/SiO2 nanofiber matrix, which enabled the resultant Cu@C/SiO2 NFMs to be applied as heterogeneous catalysts, and their catalytic performance was systematically assessed through activating persulfate for the elimination of tetracycline hydrochloride (TCH) in water. The fabricated Cu@C/SiO2 NFMs provided outstanding catalytic performance towards TCH with a high removal efficiency of 95% in 40 min and a rapid removal speed of 0.054 min-1. Moreover, the membranes could be facilely recycled through being directly separated from water without any post-processing. Such a facile strategy for preparing mesoporous and flexible metal-doped inorganic nanofibrous membranes may offer novel insights for designing new types of heterogeneous catalysts for antibiotic-containing wastewater treatment or other potential applications.