Stretchable Triboelectric Nanogenerator Based on Liquid Metal with Varying Phases.

Stretchable triboelectric nanogenerators (TENGs) represent a new class of energy-harvesting devices for powering wearable devices. However, most of them are associated with poor stretchability, low stability, and limited substrate material choices. This work presents the design and demonstration of highly stretchable and stable TENGs based on liquid metalel ectrodes with different phases. The conductive and fluidic properties of eutectic gallium-indium (EGaIn) in the serpentine microfluidic channel ensure the robust performance of the EGaIn-based TENG upon stretching over several hundred percent. The bi-phasic EGaIn (bGaIn) from oxidation lowers surface tension and increases adhesion for printing on diverse substrates with high output performance parameters. The optimization of the electrode shapes in the bGaIn-based TENGs can reduce the device footprint and weight, while enhancing stretchability. The applications of the EGaIn- and bGaIn-based TENG include smart elastic bands for human movement monitoring and smart carpets with integrated data transmission/processing modules for headcount monitoring/control. Combining the concept of origami in the paper-based bGaIn TENG can reduce the device footprint to improve output performance per unit area. The integration of bGaIn-TENG on a self-healing polymer substrate with corrosion resistance against acidic and alkaline solutions further facilitates its use in various challenging and extreme environments.

Injectable, degradable, and mechanically adaptive hydrogel induced by L-serine and allyl-functionalized chitosan with platelet-rich plasma for treating intrauterine adhesions.

The integration of barrier materials with pharmacological therapy is a promising strategy to treat intrauterine adhesions (IUAs). However, most of these materials are surgically implanted in a fixed shape and incongruence with the natural mechanical properties of the uterus, causing poor adaptability and significant discomfort to the patients. Herein, an injectable, biodegradable, and mechanically adaptive hydrogel loaded with platelet-rich plasma (PRP) is created by L­serine and allyl functionalized chitosan (ACS) to achieve efficient, comfortable, and minimally invasive treatment of IUAs. L­serine induces fast gelation and mechanical reinforcement of the hydrogel, while ACS introduces, imparting a good injectability and complaint yet strong feature to the hydrogel. This design enables the hydrogel to adapt to the complex geometry and match the mechanical properties of the uterine. Moreover, the hydrogel exhibits proper degradability, sustained growth factors (GFs) of PRP release ability, and good biocompatibility. Consequently, the hydrogel shows promising therapeutic efficacy by reducing collagen fiber deposition and facilitating endometrium cell proliferation, thereby restoring the fertility function of the uterus in an IUAs model of rats. Accordingly, the combination of L­serine and ACS-induced hydrogel with such advantages holds great potential for treating IUAs. STATEMENT OF SIGNIFICANCE: This research introduces a breakthrough in the treatment of intrauterine adhesions (IUAs) with an injectable, biodegradable and mechanically adaptive hydrogel using L­serine and allyl functionalized chitosan (ACS). Unlike traditional surgical treatments, this hydrogel uniquely conforms to the uterus's geometry and mechanical properties, offering a minimally invasive, comfortable, and more effective solution. The hydrogel is designed to release growth factors from platelet-rich plasma (PRP) sustainably, promoting tissue regeneration by enhancing collagen fiber deposition and endometrium cell proliferation. Demonstrated efficacy in a rat model of IUAs indicates its great potential to significantly improve fertility restoration treatments. This advancement represents a significant leap in reproductive medicine, promising to transform IUAs treatment with its innovative approach to achieving efficient, comfortable, and minimally invasive therapy.

Silicone Bioadhesive with Shear-Stiffening Effect: Rate-Responsive Adhesion Behavior and Wound Dressing Application.

Stimuli-responsive adhesives with on-demand adhesion capabilities are highly advantageous for facilitating wound healing. However, the triggering conditions of stimuli-responsive adhesives are cumbersome, even though some of them are detrimental to the adhesive and adjacent natural tissues. Herein, a novel stimuli-responsive adhesive called shear-stiffening adhesive (SSA) has been created by constructing a poly(diborosiloxane)-based silicone network for the first time, and SSA exhibits a rate-responsive adhesion behavior. Furthermore, we introduced bactericidal factors (PVP-I) into SSA and applied it as a wound dressing to promote the healing of infected wounds. Impressively, the wound dressing not only has excellent biocompatibility and long-term antibacterial properties but also performs well in accelerating wound healing. Therefore, this study provides a new strategy for the synthesis of intelligent adhesives with force rate response, which simplifies the triggering conditions by the force rate. Thus, SSA has great potential to be applied in wound management as an intelligent bioadhesive with on-demand adhesion performance.

Ultra-Fast-Healing Glassy Hyperbranched Plastics Capable of Restoring 26.4†MPa Tensile Strength within One Minute at Room Temperature.

The growing concern regarding widespread plastic pollution has propelled the development of sustainable self-healing plastics. Although considerable efforts have been dedicated to fabricating self-healing plastics, achieving rapid healing at room temperature is extremely challenging. Herein, we have developed an ultra-fast-healing glassy polyurethane (UGPU) by designing a hyperbranched molecular structure with a high density of multiple hydrogen bonds (H-bonds) on compliant acyclic heterochains and introducing trace water to form water bridge across the fractured surfaces. The compliant acyclic heterochains allow the dense multiple hydrogen bonds to form a frozen network, enabling tensile strength of up to 70 MPa and storage modulus of 2.5 GPa. The hyperbranched structure can drive the reorganization of the H-bonding network through the high mobility of the branched chains and terminals, thereby leading to self-healing ability at room temperature. Intriguingly, the presence of trace water vapor facilitates the formation of activated layers and the rearrangement of networks across the fractured UGPU sections, thereby enabling ultra-fast self-healing at room temperature. Consequently, the restored tensile strength after healing for 1 minute achieves a historic-record of 26.4 MPa. Furthermore, the high transparency (>90 %) and ultra-fast healing property of UGPU make it an excellent candidate for advanced optical and structural materials.

Injectable, stable, and biodegradable hydrogel with platelet-rich plasma induced by l-serine and sodium alginate for effective treatment of intrauterine adhesions.

The combination of pharmacological and physical barrier therapy is a highly promising strategy for treating intrauterine adhesions (IUAs), but there lacks a suitable scaffold that integrates good injectability, proper mechanical stability and degradability, excellent biocompatibility, and non-toxic, non-rejection therapeutic agents. To address this, a novel injectable, degradable hydrogel composed of poly(ethylene glycol) diacrylate (PEGDA), sodium alginate (SA), and l-serine, and loaded with platelet-rich plasma (PRP) (referred to as PSL-PRP) is developed for treating IUAs. l-Serine induces rapid gelation within 1 min and enhances the mechanical properties of the hydrogel, while degradable SA provides the hydrogel with strength, toughness, and appropriate degradation capabilities. As a result, the hydrogel exhibits an excellent scaffold for sustained release of growth factors in PRP and serves as an effective physical barrier. In vivo testing using a rat model of IUAs demonstrates that in situ injection of the PSL-PRP hydrogel significantly reduces fibrosis and promotes endometrial regeneration, ultimately leading to fertility restoration. The combined advantages make the PSL-PRP hydrogel very promising in IUAs therapy and in preventing adhesions in other internal tissue wounds.

Porphyrin(2.1.2.1) organopalladium complexes as efficient singlet oxygen sensitizers.

Four new non-planar and non-aromatic porphyrin organopalladium complexes were synthesized. Conformational structures and optical and electronic properties of the obtained organopalladium complexes containing meso-substituted phenyl, p-tert-butylphenyl, or pentafluorophenyl groups were fully investigated. These complexes showed potent capacity for singlet oxygen (1O2) generation under blue-light irradiation, and the 1O2 quantum yields were in the range of 41%-56%, which were comparable to that of Ru(bpy)3Cl2 (57%), and such potency made these organopalladium complexes potential 1O2 photo sensitizers for photodynamic therapy.

Insect cuticle-inspired design of sustainably sourced composite bioplastics with enhanced strength, toughness and stretch-strengthening behavior.

Insect cuticles that are mainly made of chitin, chitosan and proteins provide insects with rigid, stretchable and robust skins to defend harsh external environment. The insect cuticle therefore provides inspiration for engineering biomaterials with outstanding mechanical properties but also sustainability and biocompatibility. We herein propose a design of high-performance and sustainable bioplastics via introducing CPAP3-A1, a major structural protein in insect cuticles, to specifically bind to chitosan. Simply mixing 10w/w% bioengineered CPAP3-A1 protein with chitosan enables the formation of plastics-like, sustainably sourced chitosan/CPAP3-A1 composites with significantly enhanced strength (∼90 MPa) and toughness (∼20 MJ m -3), outperforming previous chitosan-based composites and most synthetic petroleum-based plastics. Remarkably, these bioplastics exhibit a stretch-strengthening behavior similar to the training living muscles. Mechanistic investigation reveals that the introduction of CPAP3-A1 induce chitosan chains to assemble into a more coarsened fibrous network with increased crystallinity and reinforcement effect, but also enable energy dissipation via reversible chitosan-protein interactions. Further uniaxial stretch facilitates network re-orientation and increases chitosan crystallinity and mechanical anisotropy, thereby resulting in stretch-strengthening behavior. In general, this study provides an insect-cuticle inspired design of high-performance bioplastics that may serve as sustainable and bio-friendly materials for a wide range of engineering and biomedical application potentials.

A Shear-Stiffening Mouthguard with Excellent Shock Absorption Capability and Remoldability via a Dynamic Dual Network.

Mouthguards are used to reduce injuries and the probability of them to orofacial tissues when impacted during sports. However, the usage of a mouthguard is low due to the discomfort caused by the thickness of the mouthguard. Herein, we have constructed a dynamic dual network to fabricate a shear-stiffening mouthguard with remoldability, which are called remoldable shear-stiffening mouthguards (RSSMs). Based on diboron/oxygen dative bonds, RSSMs show a shear-stiffening effect and excellent shock absorption ability, which can absorb more than 90% of the energy of a blank. Even reducing the thickness to half, RSSMs can reduce approximately 25% of the transmitted force and elongate by about 1.6-fold the buffer time compared to commercial mouthguard materials (Erkoflex and Erkoloc-pro). What is more, owing to the dynamic dual network, RSSMs show good remolding performance with unchanged shear-stiffening behavior and impact resistance, which conforms to the existing vacuum thermoforming mode. In addition, RSSMs exhibit stability in artificial saliva and biocompatibility. In conclusion, this work will broaden the range of mouthguard materials and offer a platform to apply shear-stiffening materials to biomedical applications and soft safeguarding devices.

Characterization of m6A RNA methylation mediated immune heterogeneity and functional validation in hepatocellular carcinoma.

BACKGROUND: N6 -methyladenosine (m6 A) mediates RNA modification in various biological processes. It plays a key role in hepatocellular carcinoma (HCC) through regulating methyltransferase. The present study aims to analyze the correlation between the m6 A and the immune status of HCC, and to construct an m6 A-related prognostic signature for HCC. METHODS: HCC subtypes with different m6 A modification activities were identified based on the m6 A-related genes. Lasso Cox regression was applied to construct an m6 A-related prognostic model for HCC. Then, the prognostic potential of the constructed signature was evaluated and validated in the external validation dataset. Small interfering RNAs were designed to knockdown FBXO5. CCK-8 assay, Edu staining, wound healing assay, and Transwell cell invasion assay were used to detect cell proliferation, migration, and invasion ability. RESULTS: Two m6 A-related HCC subtypes were identified. The m6 A modification active group showed an immune suppressive microenvironment compared to the m6 A modification inactive group. The differentially expressed genes (DEGs) between the HCC subtypes were screened. Enrichment analysis was performed using the DEGs. Subsequently, an m6 A-related prognostic model was established. The prognostic model performed well in both training and validation datasets. Moreover, knockdown of FBXO5, one of the genes in the prognostic model, inhibited the proliferation, migration, and invasion of HepG2 cells. CONCLUSIONS: The heterogeneity of m6 A RNA methylation is associated with immune status in HCC. The constructed m6 A-related gene-based signature can predict the prognosis of HCC patients. The genes in the prognostic model also have therapeutic potential for HCC.

Hemostatic Tranexamic Acid-Induced Fast Gelation and Mechanical Reinforcement of Polydimethylacrylamide/Carboxymethyl Chitosan Hydrogel for Hemostasis and Wound Healing.

The combinational properties with excellent mechanical properties, adhesive performance, hemostatic ability, antibacterial action, and wound healing efficacy are highly desirable for injectable hydrogels' practical applications in hemorrhage control and wound closure, but designing one single hydrogel system integrating with such properties is still difficult. Herein, a simplified yet straightforward strategy is proposed to prepare an injectable and robust poly(N,N-dimethylacrylamide) (PDMAA)/carboxymethyl chitosan (CMCS) hydrogel induced by tranexamic acid (TXA). TXA not only promotes the rapid generation of free radicals but also introduces multiple hydrogen bonds into the hydrogel network. Moreover, as a common clinical hemostatic drug, TXA itself has excellent hemostatic effects. In addition, CMCS imparts sterilization and hemostasis effects to the hydrogel, thereby promoting wound healing. Besides, the amino and carboxyl groups on TXA molecules and the hydroxyl, amino, and carboxyl groups on CMCS molecules can form multiple hydrogen bonds with wet biological tissues, leading to good wet tissue adhesion of the hydrogel. As a result, the hydrogel with excellent mechanical properties (up to 1.83 MPa at 90% compression strain), adhesion performance (up to 18.7 kPa adhesion strength to porcine skin tissue), biocompatibility, hemostatic ability, antibacterial activity, and wound healing properties can be fabricated within several minutes. These combinational advantages enable the hydrogel to efficiently stop hemorrhage (blood loss amount: 110 mg; hemostasis time: 25 s) and promote the wound healing process (wound closure rate at 2 weeks: 83%), which can be verified using rat models of liver bleeding and infected full thickness skin defect. Overall, this facile strategy to design a hydrogel incorporating such unique advantages will greatly advance the hydrogel's clinical application in rapid hemostasis and wound healing.

Mechanically robust, self-reporting and healable polyurethane elastomers by incorporating symmetric/asymmetric chain extenders.

Self-healing elastomers usually show poor mechanical properties and environmental stability, and they cannot self-report mechanical/chemical damage. Herein, an innovative design strategy is reported that combines symmetric/asymmetric chain extenders to create large yet disordered hard domains within polyurethane (PU) elastomers, enabling the integration of mechanical robustness and self-reporting and self-healing capabilities to overcome both mechanical and chemical damage. Specifically, large yet disordered hard domains were created by governing the molar contents of asymmetric fluorescent 2-(4-aminophenyl)-5-aminobenzimidazole (PABZ) and symmetric 4-aminophenyl disulfide (APDS). Such a structural feature led to a small free-volume fraction, prominent strain-induced crystallization (SIC), and high energy of dissipation, enabling the PU elastomer to display outstanding mechanical strength (60.7 MPa) and toughness (177.9 MJ m-3). Meanwhile, the loose stacking of disordered hard domains imposed small restriction on network chains and imparted the network with high relaxation dynamics, leading to high healing efficiency (97.8%). More importantly, the fluorescence intensity was stimulus-responsive and thus the PU elastomer could self-report mechanical/chemical damage and healing processes. The PU elastomer also showed potential application prospects in information encoding and encryption. Furthermore, selecting polydimethylsiloxane as one of the soft segments could effectively endow the PU elastomer with intrinsic hydrophobicity. Therefore, this work provides valuable guidance for designing multi-functional materials with anti-counterfeiting, self-reporting, and healing properties as well as high mechanical properties and hydrophobicity.

Transparent and Soft Crack-Resistant Bouligand Elastomers Inspired by Fish Scales.

Nature with its abundant source offers numerous inspirations for structural and engineering designs. The oriented membranes stacked with bouligand structures in the fish scales show an outstanding combination of high strength and crack resistance. Although the applications of hard biomimetic composites are reported, the structures are rarely utilized in soft materials. Inspired by the scales of various fishes, electrospun membranes are used and stacked to fabricate bouligand elastomers, including orthogonal-plywood, single-bouligand, and double-bouligand structures. The effects of different structures on the properties of elastomers are systematically investigated and possible mechanism is explained using finite element analysis (FEA). The stiffness and fatigue characteristics of these biomimetic elastomers with the above structures are improved compared with the original membranes, especially the elastomers with a single-bouligand structure, which can undergo 5 000 cycles at a maximum strain of 35% without complete failure. The crack only propagates to half of the width of the elastomer with remaining strength of 50% of its original strength. Moreover, the mechanical performance can be adjusted by regulating the proportion of the components. The excellent crack-resistant properties and transparency promote its various potential applications.

Thermomechanically stable supramolecular elastomers inspired by heat shock proteins.

Supramolecular polymers are usually thermomechanically unstable, as their mechanical strength decreases drastically upon heating, which is a fatal shortcoming for their application. Herein, inspired by heat shock proteins (HSPs) which enable living organisms to tolerate lethal high temperatures, we design an HSP-like response to impart a supramolecular elastomer with high thermomechanical stability. The HSP-like response relies on the reversible hydrolysis of boronic acid and the tunable association strength of boron dative bonds. As the temperature increases, the boronic acid dehydrates and transforms into boroxane. The boroxane, acting as a heat shock chemical, prevents the disintegration of the supramolecular network through formation of multiple and stronger dative bonds with imidazole-containing polymers, thereby enabling the material to retain its mechanical strength at high temperatures. Such chemical transformation and network change induced by the HSP-like response are fully reversible during the heating and cooling processes. Moreover, due to the dynamic nature of the supramolecular network, the elastomer possesses recycling and self-healing abilities.

The Interplay of Protein Hydrolysis and Ammonia in the Stability of Hevea Rubber Latex during Storage.

Natural rubber (NR) latex derived from Hevea brasiliensis is a complex colloid comprising mainly rubber hydrocarbons (latex particles) and a multitude of minor non-rubber constituents such as non-rubber particles, proteins, lipids, carbohydrates, and soluble organic and inorganic substances. NR latex is susceptible to enzymatic attack after it leaves the trees. It is usually preserved with ammonia and, to a lesser extent, with other preservatives to enhance its colloidal stability during storage. Despite numerous studies in the literature on the influence of rubber proteins on NR latex stability, issues regarding the effect of protein hydrolysis in the presence of ammonia on latex stability during storage are still far from resolved. The present work aims to elucidate the interplay between protein hydrolysis and ammoniation in NR latex stability. Both high- and low-ammonia (with a secondary preservative) NR latexes were used to monitor the changes in their protein compositions during storage. High-ammonia (FNR-A) latex preserved with 0.6% (v/v) ammonia, a low 0.1% ammonia/TMTD/ZnO (FNR-TZ) latex, and a deproteinized NR (PDNR) latex were labeled with fluorescence agents and observed using confocal laser scanning microscopy to determine their protein composition. Protein hydrolysis was confirmed via sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The results revealed that protein hydrolysis increased with the storage duration. The change in protein composition accompanying hydrolysis also allows the spatial distribution of allergenic proteins to be estimated in the latex. Concurrently, the latex stability increased with the storage duration, as measured by the latex's mechanical stability time (MST) and the zeta potential of the latex particles. As monitored by AFM, the surface roughness of the NR latex film increased markedly during extended storage compared with that of the DPNR latex, which remained smooth. These results underscore the pivotal role of ammonia in bolstering NR latex stability brought on by protein hydrolysis, which greatly impacts latex film's formation behavior. NR latex stability underpins the quality of latex-dipped goods during manufacturing, particularly those for medical gloves.

Mouthguards Based on the Shear-Stiffening Effect: Excellent Shock Absorption Ability with Softness Perception.

Mouthguards are used to prevent craniomaxillofacial injuries when collisions happen during contact and high-speed sports. However, poor compliance with mouthguard wear in athletes is attributed to discomfort because of its thickness and hardness. These drawbacks significantly restrict their protective performance for oral tissues and applications during contact sports; as a result, the incidence of craniomaxillofacial injuries increases. In this study, non-Newton material is introduced into mouthguard material and then a mouthguard with shear-stiffening behavior is fabricated, which is named the shear-stiffening mouthguard (SSM). Compared with commercial mouthguard materials (Erkoflex and Erkoloc-pro), SSMs show remarkable enhancement of shock absorption ability with an approximately 60% reduction in peak force relative to commercial materials and approximately 3-fold extensive buffer time. Moreover, Young's modulus of SSMs (average 0.48 MPa) is extremely lower compared to commercial materials (22.88 MPa for Erkoflex and 26.71 MPa for Erkoloc-pro). This manifests that SSMs have not only excellent shock absorption ability but also softness perception. Moreover, SSMs show biocompatibility in vitro. In conclusion, this work provides a platform to develop a new type of thin and soft mouthguard with a shear-stiffening effect and broadens the horizon in protecting oral tissues with shear-stiffening materials.

Omnidirectional Printing of PEDOT:PSS for High-Conductivity Spanning Structures.

Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS), a prominent conducting polymer, holds significance in both industry and academia. However, prevailing fabrication techniques struggle to build spanning features of PEDOT:PSS with both high electrical conductivity and fine resolution due to layerwise assembly in the xy plane. Here, we report an "omnidirectional printing and secondary doping" strategy to construct spanning, filamentary and out-of-plane 3D PEDOT:PSS with high conductivity. The pristine PEDOT:PSS suspension is homogeneously concentrated to form a printable ink with high solids (∼15 wt %) consisting of entangled PEDOT:PSS nanofibrils. Such ink shows a high storage modulus G' (43531 Pa) and a high yield stress τy (4325 Pa), thereby enabling omnidirectional printing. Secondary doping with sulfuric acid or other polar solvents is used to induce a synergetic process of PSS loss, conformational change, phase separation, and crystallinity enhancement in the printed structures, resulting in a remarkable enhancement of conductivity in dehydrated (65,378 S/m) and swollen (7190 S/m) states. As a proof-of-concept, 2D grids with a feature size of 15 µm and 3D overhanging arches are fabricated for high-performance transparent glass heaters and 3D interconnection, respectively. This work promises great potential for the development of advanced flexible electronics, wearable devices, and bioelectronics.

Deletion in 1p36.33-p36.32 is associated with pancytopenia: a case report.

BACKGROUND: 1P36 deletion syndrome is recognized as the most common terminal microdeletion syndrome in humans, characterized by early developmental delay and consequent intellectual disability, seizure disorder, and distinctive facial features. Variable deletion locations may attributed to phenotypic variability. However, the abnormal phenotypes of hematology are rarely reported in 1P36 deletion syndrome patients. CASE PRESENTATION: We present a case of postnatal intellectual disability accompanied by pancytopenia. Copy number variation analysis revealed a pathogenic deletion in 1p36.331p36.32 with a deletion size of 2.21 Mb. Following successful treatment with glucocorticoids, the patient was diagnosed with immuno-related hemocytopenia (IRH). DISCUSSION: The patient experienced IRH, an uncommon characteristic of 1p36 deletion syndrome. The deletion fragment of 1p36.33-p36.32, particularly the loss of GNB1 gene, has been associated with the development of pancytopenia. Genotype-phenotype correlations are valuable in identifying the genes responsible for various clinical characteristics of the syndrome by associating phenotypic variation with specific genes located within the chromosome deletion region. Genome sequencing is recommended in cases where clinical manifestations indicate the presence of a genetic disorder but pose diagnostic challenges.

Amino acid-induced rapid gelation and mechanical reinforcement of hydrogels with low-hysteresis and self-recoverable and fatigue-resistant properties.

Hydrogels with rapid gelation ability and robust mechanical properties are highly desirable for nascent applications in biomedical, wearable electronic, industrial and agricultural fields. However, current rapid-gelation hydrogels are compromised by poor mechanical properties, complex design of precursor molecular structures and limited precursor species. Herein, we propose a facile and universal strategy to achieve rapid gelation, strengthening and toughening of free-radical polymerized hydrogels by introducing cheap and accessible amino acids. Amino acids not only activate persulfate to quickly produce free radicals and thus induce fast free radical polymerization, but also can form strong hydrogen bonds with the network chains to strengthen and toughen the hydrogels. For example, with the presence of L-serine, the acrylamide (AM) monomer shows rapid gelation within tens of seconds, and moreover the resulting hydrogel reaches a tensile strength of 0.45 MPa and a breaking strain of 2060%. More importantly, owing to the extremely dynamic feature of the hydrogen bonds between L-serine molecules and network chains, the hydrogel possesses the advantages of low hysteresis, rapid self-recovery capability and outstanding fatigue resistance. Furthermore, this strategy is general to a wide range of amino acids and monomers. We also demonstrate that this rapid, controllable and universal strategy for the fabrication of mechanically robust hydrogels holds tremendous potential for diverse practical applications, such as flexible electronic sensors and ultraviolet (UV)-blocking artificial skins.

New insights from trio whole-exome sequencing in the children with kidney disease: A single-center retrospective cohort study.

BACKGROUND: Kidney disease of children markedly affects their health and development. Limited clinical data of early-stage kidney disease render a tremendous challenge for the accurate diagnosis. Trio whole-exome sequencing (Trio-WES) is emerging as a first-line diagnostic strategy in pediatric kidney disease, and shows important implications for the precision medicine strategies of children with kidney disease. METHODS: Trio-WES was performed in 133 Chinese children with kidney disease and their parents. The results for casual variants in genes known to cause kidney disease were analyzed. We further assessed the genetic diagnostic yield and the clinical implications of genetic testing. RESULTS: An overall diagnostic yield of 52.63% (70/133) was found, and the diagnostic rates ranged from 44.74% to 59.62% in different clinical phenotypes. The diagnostic yield of the three groups of simple proteinuria, renal insufficiency, and "other" was 50%, 50%, and 54.55%, respectively. Eight-seven diagnostic variants were identified in 70 probands with variants spanning 30 genes. The top 7 genes with diagnostic variants were COL4A5 (23, 26.44%), COL4A4 (13, 14.94%), ADCK4 (7, 8.05%), CLCN5 (3, 3.45%), ACE (3, 3.45%), PKD1 (3, 3.45%), and SLC12A3 (3, 3.45%), accounting for 63.22% of all variations in the cohort. CONCLUSIONS: The retrospective cohort study summarized the clinical utility of genetic testing in 133 probands, and expanded the phenotypic and genetic profiles of kidney disease in children. Trio-WES is an efficient diagnostic tool for children with kidney disease, which facilitates the clinical diagnosis and treatment. Our findings have important implications for the precise diagnosis of childhood nephropathy and may provide clinical guideline for disease management.