Tailor-Made Gold Nanomaterials for Applications in Soft Bioelectronics and Optoelectronics.

In modern nanoscience and nanotechnology, gold nanomaterials are indispensable building blocks that have demonstrated a plethora of applications in catalysis, biology, bioelectronics, and optoelectronics. Gold nanomaterials possess many appealing material properties, such as facile control over their size/shape and surface functionality, intrinsic chemical inertness yet with high biocompatibility, adjustable localized surface plasmon resonances, tunable conductivity, wide electrochemical window, etc. Such material attributes have been recently utilized for designing and fabricating soft bioelectronics and optoelectronics. This motivates to give a comprehensive overview of this burgeoning field. The discussion of representative tailor-made gold nanomaterials, including gold nanocrystals, ultrathin gold nanowires, vertically aligned gold nanowires, hard template-assisted gold nanowires/gold nanotubes, bimetallic/trimetallic gold nanowires, gold nanomeshes, and gold nanosheets, is begun. This is followed by the description of various fabrication methodologies for state-of-the-art applications such as strain sensors, pressure sensors, electrochemical sensors, electrophysiological devices, energy-storage devices, energy-harvesting devices, optoelectronics, and others. Finally, the remaining challenges and opportunities are discussed.

Self-supervised context-aware correlation filter for robust landmark tracking in liver ultrasound sequences.

OBJECTIVES: Respiratory motion-induced displacement of internal organs poses a significant challenge in image-guided radiation therapy, particularly affecting liver landmark tracking accuracy. METHODS: Addressing this concern, we propose a self-supervised method for robust landmark tracking in long liver ultrasound sequences. Our approach leverages a Siamese-based context-aware correlation filter network, trained by using the consistency loss between forward tracking and back verification. By effectively utilizing both labeled and unlabeled liver ultrasound images, our model, Siam-CCF , mitigates the impact of speckle noise and artifacts on ultrasonic image tracking by a context-aware correlation filter. Additionally, a fusion strategy for template patch feature helps the tracker to obtain rich appearance information around the point-landmark. RESULTS: Siam-CCF achieves a mean tracking error of 0.79 ± 0.83 mm at a frame rate of 118.6 fps, exhibiting a superior speed-accuracy trade-off on the public MICCAI 2015 Challenge on Liver Ultrasound Tracking (CLUST2015) 2D dataset. This performance won the 5th place on the CLUST2015 2D point-landmark tracking task. CONCLUSIONS: Extensive experiments validate the effectiveness of our proposed approach, establishing it as one of the top-performing techniques on the CLUST2015 online leaderboard at the time of this submission.

ROS-induced oxidative stress and mitochondrial dysfunction: a possible mechanism responsible for noise-induced ribbon synaptic damage.

Evidence suggests that damage to the ribbon synapses (RS) may be the main cause of auditory dysfunction in noise-induced hearing loss (NIHL). Oxidative stress is implicated in the pathophysiology of synaptic damage. However, the relationship between oxidative stress and RS damage in NIHL remains unclear. To investigate the hypothesis that noise-induced oxidative stress is a key factor in synaptic damage within the inner ear, we conducted a study using mice subjected to single or repeated noise exposure (NE). We assessed auditory function using auditory brainstem response (ABR) test and examined cochlear morphology by immunofluorescence staining. The results showed that mice that experienced a single NE exhibited a threshold shift and recovered within two weeks. The ABR wave I latencies were prolonged, and the amplitudes decreased, suggesting RS dysfunction. These changes were also demonstrated by the loss of RS as evidenced by immunofluorescence staining. However, we observed threshold shifts that did not return to baseline levels following secondary NE. Additionally, ABR wave I latencies and amplitudes exhibited notable changes. Immunofluorescence staining indicated not only severe damage to RS but also loss of outer hair cells. We also noted decreased T-AOC, ATP, and mitochondrial membrane potential levels, alongside increased hydrogen peroxide concentrations post-NE. Furthermore, the expression levels of 4-HNE and 8-OHdG in the cochlea were notably elevated. Collectively, our findings suggest that the production of reactive oxygen species leads to oxidative damage in the cochlea. This mitochondrial dysfunction consequently contributes to the loss of RS, precipitating an early onset of NIHL.

Phenethylammonium bromide interlayer for high-performance red quantum-dot light emitting diodes.

Interfacial modification is vital to boost the performance of colloidal quantum-dot light-emitting diodes (QLEDs). We introduce phenethylammonium bromide (PEABr) as an interlayer to reduce the trap states and exciton quenching at the interface between the emitting layer (EML) with CdSe/ZnS quantum-dots and the electron transport layer (ETL) with ZnMgO. The presence of PEABr separates the EML and the ETL and thus passivates the surface traps of ZnMgO. Moreover, the interfacial modification also alleviates electron injection, leading to more improved carrier injection balance. Consequently, the external quantum efficiency of the PEABr-based red QLED reached 27.6%, which outperformed those of the previously reported devices. Our results indicate that the halide ion salts are promising to balance charge carrier injection and reduce exciton quenching in the QLEDs.

Materials-Driven Soft Wearable Bioelectronics for Connected Healthcare.

In the era of Internet-of-things, many things can stay connected; however, biological systems, including those necessary for human health, remain unable to stay connected to the global Internet due to the lack of soft conformal biosensors. The fundamental challenge lies in the fact that electronics and biology are distinct and incompatible, as they are based on different materials via different functioning principles. In particular, the human body is soft and curvilinear, yet electronics are typically rigid and planar. Recent advances in materials and materials design have generated tremendous opportunities to design soft wearable bioelectronics, which may bridge the gap, enabling the ultimate dream of connected healthcare for anyone, anytime, and anywhere. We begin with a review of the historical development of healthcare, indicating the significant trend of connected healthcare. This is followed by the focal point of discussion about new materials and materials design, particularly low-dimensional nanomaterials. We summarize material types and their attributes for designing soft bioelectronic sensors; we also cover their synthesis and fabrication methods, including top-down, bottom-up, and their combined approaches. Next, we discuss the wearable energy challenges and progress made to date. In addition to front-end wearable devices, we also describe back-end machine learning algorithms, artificial intelligence, telecommunication, and software. Afterward, we describe the integration of soft wearable bioelectronic systems which have been applied in various testbeds in real-world settings, including laboratories that are preclinical and clinical environments. Finally, we narrate the remaining challenges and opportunities in conjunction with our perspectives.

Biomimetic Electronic Skin through Hierarchical Polymer Structural Design.

Human skin comprises multiple hierarchical layers that perform various functions such as protection, sensing, and structural support. Developing electronic skin (E-skin) with similar properties has broad implications in health monitoring, prosthetics, and soft robotics. While previous efforts have predominantly concentrated on sensory capabilities, this study introduces a hierarchical polymer system that not only structurally resembles the epidermis-dermis bilayer structure of skin but also encompasses sensing functions. The system comprises a polymeric hydrogel, representing the "dermis", and a superimposed nanoporous polymer film, forming the "epidermis". Within the film, interconnected nanoparticles mimic the arrangement of interlocked corneocytes within the epidermis. The fabrication process employs a robust in situ interfacial precipitation polymerization of specific water-soluble monomers that become insoluble during polymerization. This process yields a hybrid layer establishing a durable interface between the film and hydrogel. Beyond the structural mimicry, this hierarchical structure offers functionalities resembling human skin, which includes (1) water loss protection of hydrogel by tailoring the hydrophobicity of the upper polymer film; (2) tactile sensing capability via self-powered triboelectric nanogenerators; (3) built-in gold nanowire-based resistive sensor toward temperature and pressure sensing. This hierarchical polymeric approach represents a potent strategy to replicate both the structure and functions of human skin in synthetic designs.

Exploring the efficacious constituents and underlying mechanisms of sini decoction for sepsis treatment through network pharmacology and multi-omics.

BACKGROUND: Traditional Chinese medicine prescription sini decoction (SND) can alleviate inflammation, improve microcirculation, and modulate immune status in sepsis patients. However, its underlying mechanisms remain unclear, and therapeutic effects may vary among individuals. PURPOSE: Through a comprehensive and systematic network pharmacology analysis, the purpose of this study is to investigate the therapeutic mechanisms of SND in treating sepsis. METHODS: An analysis of WGCNA identified CX3CR1 as a key gene influencing sepsis prognosis. A drug-active component-target network for SND was created using the traditional Chinese medicine systems pharmacology (TCMSP) database and Cytoscape software. Shared targets between SND and CX3CR1 high-expression gene modules were found through the GEO database. Gene module functionality was analyzed using GO, KEGG, GSEA, and GSVA. Unsupervised clustering of sepsis patients was performed based on the ferroptosis gene set, and immune cell interactions and mechanisms were explored using CIBERSORT, single-cell sequencing, and intercellular communication analysis. RESULTS: This study demonstrates that high expression of CX3CR1 improves survival rates in sepsis patients and is associated with immune cell signaling pathways. SND contains 116 active components involved in oxidative stress and lipid metabolism pathways. HMOX1, a co-expressed gene in SND and CX3CR1 high-expression gene module, plays a crucial role in sepsis survival. Unsupervised clustering analysis classified sepsis patients into three clusters based on the ferroptosis gene set, revealing differences in immune cell expression and involvement in heme metabolism pathways. Notably, intercellular interactions among immune cells primarily occur through paracrine and autocrine mechanisms in MIF, GALECTIN, and IL16 signaling pathways, modulating the immune-inflammatory microenvironment in sepsis. CONCLUSIONS: This study identifies CX3CR1 as a crucial molecule impacting sepsis prognosis through WGCNA analysis. It reveals that SND's active component, quercetin and kaempferol, target HMOX1 via related pathways to regulate heme metabolism, reduce inflammation, inhibit ferroptosis, and improve immune function, ultimately improving sepsis prognosis. These findings offer a solid pharmacological foundation and potential therapeutic targets for SND in treating sepsis.

Factors influencing early mobilisation for patients undergoing pancreatic surgery from multiple perspectives: a qualitative descriptive study.

OBJECTIVES: Despite early mobilisation as a key component of enhanced recovery after surgery pathways for pancreatic surgery, the implementation of early mobilisation remains unsatisfactory. What factors influence the implementation of early mobilisation from the lens of all stakeholders is unclear. The aim of this study was to identify the influencing factors of early mobilisation in pancreatic surgery from the perspective of patients, family members and health professionals. DESIGN: A qualitative descriptive design using individual interviews and focus groups. SETTING AND PARTICIPANTS: Twenty-two patients undergoing pancreatic surgery, 10 family members and 10 healthcare professionals from a large university teaching hospital in China. METHODS: We collected data on participants' views on factors influencing early mobilisation after pancreatic surgery. Two researchers independently reviewed the transcripts and emergent coding. The data were analysed using qualitative content analysis. RESULTS: Three main categories that influenced the implementation of early mobilisation in pancreatic surgery were identified: (1) attitude towards early postoperative mobilisation (eg, perceived advantages or disadvantages of early mobilisation), (2) subjective norm (eg, impact from health professionals, family members and fellow patients) and (3) perceived behavioural control (eg, knowledge, abilities, resources and environment). CONCLUSION: Factors influencing early mobilisation are diverse and multidimensional. The successful implementation of early mobilisation requires the dedication of both patients and healthcare professionals.

Visualizing the dynamic mechanical power and time burden of mechanical ventilation patients: an analysis of the MIMIC-IV database.

BACKGROUND: Limiting driving pressure and mechanical power is associated with reduced mortality risk in both patients with and without acute respiratory distress syndrome. However, it is still poorly understood how the intensity of mechanical ventilation and its corresponding duration impact the risk of mortality. METHODS: Critically ill patients who received mechanical ventilation were identified from the Medical Information Mart for Intensive Care (MIMIC)-IV database. A visualization method was developed by calculating the odds ratio of survival for all combinations of ventilation duration and intensity to assess the relationship between the intensity and duration of mechanical ventilation and the mortality risk. RESULTS: A total of 6251 patients were included. The color-coded plot demonstrates the intuitive concept that episodes of higher dynamic mechanical power can only be tolerated for shorter durations. The three fitting contour lines represent 0%, 10%, and 20% increments in the mortality risk, respectively, and exhibit an exponential pattern: higher dynamic mechanical power is associated with an increased mortality risk with shorter exposure durations. CONCLUSIONS: Cumulative exposure to higher intensities and/or longer duration of mechanical ventilation is associated with worse outcomes. Considering both the intensity and duration of mechanical ventilation may help evaluate patient outcomes and guide adjustments in mechanical ventilation to minimize harmful exposure.

Effects of autophagy inhibitor 3-methyladenine on a diabetic mice model.

AIM: To investigate the role of autophagy inhibitor 3-methyladenine (3-MA) on a diabetic mice model (DM) and the potential mechanism. METHODS: Male C57BL/6J mice were randomly divided into a normal control group (NC group) and an DM group. DM were induced by multiple low-dose intraperitoneal injection of streptozotocin (STZ) 60 mg/kg·d for 5 consecutive days. DM mice were randomly subdivided into untreated group (DM group), 3-MA (10 mg/kg·d by gavage) treated group (DM+3-MA group) and chloroquine (CQ; 50 mg/kg by intraperitoneal injection) treated group (DM+CQ group). The fasting blood glucose (FBG) levels were recorded every week. At the end of experiment, retinal samples were collected. The expression levels of pro-apoptotic proteins cleaved caspase-3, cleaved poly ADP-ribose polymerase 1 (PARP1) and Bax, anti-apoptotic protein Bcl-2, fibrosis-associated proteins Fibronectin and type 1 collagen α1 chain (COL1A1), vascular endothelial growth factor (VEGF), inflammatory factors interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, as well as autophagy related proteins LC3, Beclin-1 and P62 were determined by Western blotting. The oxidative stress indicators 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) were detected by commercial kits. RESULTS: Both 3-MA and CQ had short-term hypoglycemic effect on FBG and reduced the expression of VEGF and inflammatory factors IL-1ß and TNF-α in DM mice. 3-MA also significantly alleviated oxidative stress indicators 8-OHdG and MDA, decreased the expression of fibrosis-related proteins Fibronectin and COL1A1, pro-apoptotic proteins cleaved caspase-3, cleaved PARP1, as well as the ratio of Bax/Bcl-2. CQ had no significant impact on the oxidative stress indicators, fibrosis, and apoptosis related proteins. The results of Western blotting for autophagy related proteins showed that the ratio of LC3 II/LC3 I and the expression of Beclin-1 in the retina of DM mice were decreased by 3-MA treatment, and the expression of P62 was further increased by CQ treatment. CONCLUSION: 3-MA has anti-apoptotic and anti-fibrotic effects on the retina of DM mice, and can attenuate retinal oxidative stress, VEGF expression and the production of inflammatory factors in the retina of DM mice. The underlying mechanism of the above effects of 3-MA may be related to its inhibition of early autophagy and hypoglycemic effect.

Survival Prediction After Transarterial Chemoembolization for Hepatocellular Carcinoma: a Deep Multitask Survival Analysis Approach.

The accurate prediction of postoperative survival time of patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) is important for postoperative health care. Survival analysis is a common method used to predict the occurrence time of events of interest in the medical field. At present, the mainstream survival analysis models, such as the Cox proportional risk model, should make strict assumptions about the potential random process to solve the censored data, thus potentially limiting their application in clinical practice. In this paper, we propose a novel deep multitask survival model (DMSM) to analyze HCC survival data. Specifically, DMSM transforms the traditional survival time prediction problem of patients with HCC into a survival probability prediction problem at multiple time points and applies entropy regularization and ranking loss to optimize a multitask neural network. Compared with the traditional methods of deleting censored data and strong hypothesis, DMSM makes full use of all the information in the censored data but does not need to make any assumption. In addition, we identify the risk factors affecting the prognosis of patients with HCC and visualize the importance of ranking these factors. On the basis of the analysis of a real dataset of patients with BCLC stage B HCC, experimental results on three different validation datasets show that the DMSM achieves competitive performance with concordance index of 0.779, 0.727, and 0.780 and integrated Brier score (IBS) of 0.172, 0.138, and 0.135, respectively. Our DMSM has a comparatively small standard deviation (0.002, 0.002, and 0.003) for IBS of bootstrapping 100 times. The DMSM we proposed can be utilized as an effective survival analysis model and provide an important means for the accurate prediction of postoperative survival time of patients with BCLC stage B HCC.

Alterations in the microenvironment and the effects produced of TRPV5 in osteoporosis.

The pathogenesis of osteoporosis involves multiple factors, among which alterations in the bone microenvironment play a crucial role in disrupting normal bone metabolic balance. Transient receptor potential vanilloid 5 (TRPV5), a member of the TRPV family, is an essential determinant of the bone microenvironment, acting at multiple levels to influence its properties. TRPV5 exerts a pivotal influence on bone through the regulation of calcium reabsorption and transportation while also responding to steroid hormones and agonists. Although the metabolic consequences of osteoporosis, such as loss of bone calcium, reduced mineralization capacity, and active osteoclasts, have received significant attention, this review focuses on the changes in the osteoporotic microenvironment and the specific effects of TRPV5 at various levels.

Wearable Smart Bandage-Based Bio-Sensors.

Bandage is a well-established industry, whereas wearable electronics is an emerging industry. This review presents the bandage as the base of wearable bioelectronics. It begins with introducing a detailed background to bandages and the development of bandage-based smart sensors, which is followed by a sequential discussion of the technical characteristics of the existing bandages, a more practical methodology for future applications, and manufacturing processes of bandage-based wearable biosensors. The review then elaborates on the advantages of basing the next generation of wearables, such as acceptance by the customers and system approvals, and disposal.

Hierarchically resistive skins as specific and multimetric on-throat wearable biosensors.

Resistive skin biosensors refer to a class of imperceptible wearable devices for health monitoring and human-machine interfacing, in which conductive materials are deposited onto or incorporated into an elastomeric polymeric sheet. A wide range of resistive skins has been developed so far to detect a wide variety of biometric signals including blood pressure, skin strain, body temperature and acoustic vibrations; however, they are typically non-specific, with one resistive signal corresponding to a single type of biometric data (one-mode sensors). Here we show a hierarchically resistive skin sensor made of a laminated cracked platinum film, vertically aligned gold nanowires and a percolated gold nanowire film, all integrated into a single sensor. As a result, hierarchically resistive skin displays a staircase-shaped resistive response to tensile strain, with distinct sensing regimes associated to a specific active material. We show that we can, through one resistive signal, identify up to five physical or physiological activities associated with the human throat speech: heartbeats, breathing, touch and neck movement (that is, a multimodal sensor). We develop a frequency/amplitude-based neural network, Deep Hybrid-Spectro, that can automatically disentangle multiple biometrics from a single resistive signal. This system can classify 11 activities-with different combinations of speech, neck movement and touch-with an accuracy of 92.73 ± 0.82% while simultaneously measuring respiration and heart rates. We validated the classification accuracy of several biometrics with an overall accuracy of >82%, demonstrating the generality of our concept.

Effects of daphnetin on the mechanism of epithelial-mesenchymal transition induced by HMGB1 in human lung adenocarcinoma cells (A549 cell line).

As a cancer with the highest incidence in recent years, lung cancer is mainly composed of three diseases: non-small cell lung cancer, small cell lung cancer and neuroendocrine tumor. The morbidity and mortality of this malignant tumor are the highest in both male and female populations worldwide. In my country, lung cancer has become the most common cancer disease and the leading cause of cancer death, so it is extremely important to find lung cancer therapeutic targets. Based on previous studies, we speculated that the TLR4-Myd88-NFκB pathway may be involved in hmgb1-induced EMT in A549 cells, and daphnetin may also inhibit hmgb1-induced EMT through the TLR4-Myd88-NFκB pathway in A549 cells, but related studies have not linked it to hmgb1-induced EMT. Therefore, the innovation of this study is to test these two conjectures and analyze how daphnetin affects the epithelial-mesenchymal transition (EMT) mechanism induced by HMGB1 in human lung adenocarcinoma cells (A549 cell line), aiming at lung adenocarcinoma cells, foundation for clinical treatment. The proliferation rate and the migrating cell number presented an obvious decrease in the HMGB1+TLR4-shRNA group and the HMGB1+daphnetin group relative to the HMGB1 group (P < 0.0001). The intracellular expression of TLR4, Myd88, NFκB, vimentin and snail1 proteins were significantly decreased (P < 0.001), while that of E-cadherin presented a remarkable increase (P < 0.001) in the HMGB1+TLR4-shRNA and HMGB1+daphnetin group compared with the HMGB1 group. TLR4-MyD88-NFκB pathway is associated with HMGB1-induced EMT in A549 cells. Daphnetin had an inhibitory effect on HMGB1-induced EMT via the TLR4-Myd88-NF-κB pathway in A549 cells.

[Research Progress in the Effect of Sleep Deprivation on Working Memory and Its Mechanisms].

The incidence of sleep deprivation is increasing year by year and people are also paying more attention to the effects of sleep deprivation on the human body and on cognition. In addition, working memory is the foundation of many advanced cognitive functions. Therefore, we reviewed, herein, the relevant research literature on the influence of sleep deprivation on working memory, the relevant influencing factors, and possible mechanisms of action, intending to acquire a more thorough understanding of the effects of sleep deprivation on working memory and to provide evidence for scientific and sound strategies of sleep.

The magnitude, but not the duration of elevated central venous pressure is associated with mortality in sepsis patients: An analysis of the MIMIC-IV database.

BACKGROUND: It is unclear whether the magnitude and duration of elevated central venous pressure (ECVP) greater than ten mmHg has the same impact on mortality in sepsis patients. METHODS: Critically ill patients with sepsis were identified from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The duration and the magnitude of ECVP were calculated. Normalized ECVP load was defined as the ECVP load (the sum of ECVP value times its duration) divided by the total duration of ECVP. The primary endpoint was 28-day mortality. Kaplan-Meier survival analysis was used to compare survival between patients with high or low normalized ECVP load. RESULTS: A total of 1071 sepsis patients were included. Higher normalized ECVP load was associated with higher mortality rate; in contrast, the duration of ECVP was not associated with mortality. A linear relationship between normalized ECVP load and mortality was identified. Patients with higher normalized ECVP load had less urine output and more positive fluid balance. CONCLUSION: The magnitude, but not the duration of ECVP, is associated with mortality in sepsis patients. ECVP should be considered as a valuable and easily accessible safety parameter during fluid resuscitation.

Pd-conformally coated, one-end-embedded gold nanowire percolation network for intrinsically stretchable, epidermal tattoo fuel cell.

Soft, conformal and wearable epidermal fuel cells may offer promising energy solutions to power next-generation on-skin electronics on-demand anytime anywhere. However, it is non-trivial to design intrinsically stretchable electrode in order to maintain the fuel cell performance under real-world and dynamic mechanical deformations. Here, we present a tattoo-like epidermal fuel cell based on Pd conformally-coated, one-end-embedded percolation gold nanowire (EP-AuNW/EP-AuPdNW) networks, which are in essence the combination of in-plane percolation conductivity and out-plane anisotropic conductivity. Both EP-AuNW and EP-AuPdNW are intrinsically stretchable conductors for anode and cathode in fuel cell. Compared to non-conformal counterparts, a 6-times greater power density was achieved for conformal system. Importantly, EP-NW based fuel cell can function under various mechanical deformations including stretching, compression, bending, and twisting; the power density showed negligible changes to the tensile strain up to ∼50% and could maintain its 75% performance even under 80% strain. Furthermore, a dragon-tattoo epidermal fuel cell was fabricated, demonstrating on-demand power generation with real-world ethanol sources.

Up-regulation of the human-specific CHRFAM7A gene protects against renal fibrosis in mice with obstructive nephropathy.

Renal fibrosis is a major factor in the progression of chronic kidney diseases. Obstructive nephropathy is a common cause of renal fibrosis, which is also accompanied by inflammation. To explore the effect of human-specific CHRFAM7A expression, an inflammation-related gene, on renal fibrosis during obstructive nephropathy, we studied CHRFAM7A transgenic mice and wild type mice that underwent unilateral ureteral obstruction (UUO) injury. Transgenic overexpression of CHRFAM7A gene inhibited UUO-induced renal fibrosis, which was demonstrated by decreased fibrotic gene expression and collagen deposition. Furthermore, kidneys from transgenic mice had reduced TGF-ß1 and Smad2/3 expression following UUO compared with those from wild type mice with UUO. In addition, the overexpression of CHRFAM7A decreased release of inflammatory cytokines in the kidneys of UUO-injured mice. In vitro, the overexpression of CHRFAM7A inhibited TGF-ß1-induced increase in expression of fibrosis-related genes in human renal tubular epithelial cells (HK-2 cells). Additionally, up-regulated expression of CHRFAM7A in HK-2 cells decreased TGF-ß1-induced epithelial-mesenchymal transition (EMT) and inhibited activation f TGF-ß1/Smad2/3 signalling pathways. Collectively, our findings demonstrate that overexpression of the human-specific CHRFAM7A gene can reduce UUO-induced renal fibrosis by inhibiting TGF-ß1/Smad2/3 signalling pathway to reduce inflammatory reactions and EMT of renal tubular epithelial cells.

Co-transduction of dual-adeno-associated virus vectors in the neonatal and adult mouse utricles.

Adeno-associated virus (AAV)-mediated gene transfer is an efficient method of gene over-expression in the vestibular end organs. However, AAV has limited usefulness for delivering a large gene, or multiple genes, due to its small packaging capacity (< 5 kb). Co-transduction of dual-AAV vectors can be used to increase the packaging capacity for gene delivery to various organs and tissues. However, its usefulness has not been well validated in the vestibular sensory epithelium. In the present study, we characterized the co-transduction of dual-AAV vectors in mouse utricles following inoculation of two AAV-serotype inner ear (AAV-ie) vectors via canalostomy. Firstly, co-transduction efficiencies were compared between dual-AAV-ie vectors using two different promoters: cytomegalovirus (CMV) and CMV early enhancer/chicken ß-actin (CAG). In the group of dual AAV-ie-CAG vectors, the co-transduction rates for striolar hair cells (HCs), extrastriolar HCs, striolar supporting cells (SCs), and extrastriolar SCs were 23.14 ± 2.25%, 27.05 ± 2.10%, 57.65 ± 7.21%, and 60.33 ± 5.69%, respectively. The co-transduction rates in the group of dual AAV-ie-CMV vectors were comparable to those in the dual AAV-ie-CAG group. Next, we examined the co-transduction of dual-AAV-ie-CAG vectors in the utricles of neonatal mice and damaged adult mice. In the neonatal mice, co-transduction rates were 52.88 ± 3.11% and 44.93 ± 2.06% in the striolar and extrastriolar HCs, respectively, which were significantly higher than those in adult mice. In the Pou4f3+/DTR mice, following diphtheria toxin administration, which eliminated most HCs and spared the SCs, the co-transduction rate of SCs was not significantly different to that of normal utricles. Transgene expression persisted for up to 3 months in the adult mice. Furthermore, sequential administration of two AAV-ie-CAG vectors at an interval of 1 week resulted in a higher co-transduction rate in HCs than concurrent delivery. The auditory brainstem responses and swim tests did not reveal any disruption of auditory or vestibular function after co-transduction with dual-AAV-ie vectors. In conclusion, dual-AAV-ie vectors allow efficient co-transduction in the vestibular sensory epithelium and facilitate the delivery of large or multiple genes for vestibular gene therapy.