Investigation of a chondroitin sulfate-based bioactive coating for neural interface applications.

Invasive neural implants allow for high-resolution bidirectional communication with the nervous tissue and have demonstrated the ability to record neural activity, stimulate neurons, and sense neurochemical species with high spatial selectivity and resolution. However, upon implantation, they are exposed to a foreign body response which can disrupt the seamless integration of the device with the native tissue and lead to deterioration in device functionality for chronic implantation. Modifying the device surface by incorporating bioactive coatings has been a promising approach to camouflage the device and improve integration while maintaining device performance. In this work, we explored the novel application of a chondroitin sulfate (CS) based hydrophilic coating, with anti-fouling and neurite-growth promoting properties for neural recording electrodes. CS-coated samples exhibited significantly reduced protein-fouling in vitro which was maintained for up to 4-weeks. Cell culture studies revealed a significant increase in neurite attachment and outgrowth and a significant decrease in microglia attachment and activation for the CS group as compared to the control. After 1-week of in vivo implantation in the mouse cortex, the coated probes demonstrated significantly lower biofouling as compared to uncoated controls. Like the in vitro results, increased neuronal population (neuronal nuclei and neurofilament) and decreased microglial activation were observed. To assess the coating's effect on the recording performance of silicon microelectrodes, we implanted coated and uncoated electrodes in the mouse striatum for 1 week and performed impedance and recording measurements. We observed significantly lower impedance in the coated group, likely due to the increased wettability of the coated surface. The peak-to-peak amplitude and the noise floor levels were both lower in the CS group compared to the controls, which led to a comparable signal-to-noise ratio between the two groups. The overall single unit yield (% channels recording a single unit) was 74% for the CS and 67% for the control group on day 1. Taken together, this study demonstrates the effectiveness of the polysaccharide-based coating in reducing biofouling and improving biocompatibility for neural electrode devices.

A novel conductive microtubule hydrogel for electrical stimulation of chronic wounds based on biological electrical wires.

Electrical stimulation (ES) is considered a promising therapy for chronic wounds via conductive dressing. However, the lack of a clinically suitable conductive dressing is a serious challenge. In this study, a suitable conductive biomaterial with favorable biocompatibility and conductivity was screened by means of an inherent structure derived from the body based on electrical conduction in vivo. Ions condensed around the surface of the microtubules (MTs) derived from the cell's cytoskeleton are allowed to flow in the presence of potential differences, effectively forming a network of biological electrical wires, which is essential to the bioelectrical communication of cells. We hypothesized that MT dressing could improve chronic wound healing via the conductivity of MTs applied by ES. We first developed an MT-MAA hydrogel by a double cross-linking method using UV and calcium chloride to improve chronic wound healing by ES. In vitro studies showed good conductivity, mechanical properties, biocompatibility, and biodegradability of the MT-MAA hydrogel, as well as an elevated secretion of growth factors with enhanced cell proliferation and migration ability in response to ES. The in vivo experimental results from a full-thickness diabetic wound model revealed rapid wound closure within 7d in C57BL/6J mice, and the wound bed dressed by the MT-MAA hydrogel was shown to have promoted re-epithelization, enhanced angiogenesis, accelerated nerve growth, limited inflammation phases, and improved antibacterial effect under the ES treatment. These preclinical findings suggest that the MT-MAA hydrogel may be an ideal conductive dressing for chronic wound healing. Furthermore, biomaterials based on MTs may be also promising for treating other diseases.

[Analysis of imaging characteristics and effectiveness of cervical spondylotic myelopathy with cervical kyphosis].

Objective: To investigate the imaging characteristics of cervical kyphosis and spinal cord compression in cervical spondylotic myelopathy (CSM) with cervical kyphosis and the influence on effectiveness. Methods: The clinical data of 36 patients with single-segment CSM with cervical kyphosis who were admitted between January 2020 and December 2022 and met the selection criteria were retrospectively analyzed. The patients were divided into 3 groups according to the positional relationship between the kyphosis focal on cervical spine X-ray film and the spinal cord compression point on MRI: the same group (group A, 20 cases, both points were in the same position), the adjacent group (group B, 10 cases, both points were located adjacent to each other), and the separated group (group C, 6 cases, both points were located >1 vertebra away from each other). There was no significant difference between groups ( P>0.05) in baseline data such as gender, age, body mass index, lesion segment, disease duration, and preoperative C 2-7 angle, C 2-7 sagittal vertical axis (C 2-7 SVA), C 7 slope (C 7S), kyphotic Cobb angle, fusion segment height, and Japanese Orthopedic Association (JOA) score. The patients underwent single-segment anterior cervical discectomy with fusion (ACDF). The occurrence of postoperative complications was recorded; preoperatively and at last follow-up, the patients' neurological function was evaluated using the JOA score, and the sagittal parameters (C 2-7 angle, C 2-7 SVA, C 7S, kyphotic Cobb angle, and height of the fused segments) were measured on cervical spine X-ray films and MRI and the correction rate of the cervical kyphosis was calculated; the correlation between changes in cervical sagittal parameters before and after operation and the JOA score improvement rate was analyzed using Pearson correlation analysis. Results: In 36 patients, only 1 case of dysphagia occurred in group A, and the dysphagia symptoms disappeared at 3 days after operation, and the remaining patients had no surgery-related complications during the hospitalization. All patients were followed up 12-42 months, with a mean of 20.1 months; the difference in follow-up time between the groups was not significant ( P>0.05). At last follow-up, all the imaging indicators and JOA scores of patients in the 3 groups were significantly improved when compared with preoperative ones ( P<0.05). The correction rate of cervical kyphosis in group A was significantly better than that in group C, and the improvement rate of JOA score was significantly better than that in groups B and C, all showing significant differences ( P<0.05), and there was no significant difference between the other groups ( P>0.05). The correlation analysis showed that the improvement rate of JOA score was negatively correlated with C 2-7 angle and kyphotic Cobb angle at last follow-up ( r=-0.424, P=0.010; r=-0.573, P<0.001), and positively correlated with the C 7S and correction rate of cervical kyphosis at last follow-up ( r=0.336, P=0.045; r=0.587, P<0.001), and no correlation with the remaining indicators ( P>0.05). Conclusion: There are three main positional relationships between the cervical kyphosis focal and the spinal cord compression point on imaging, and they have different impacts on the effectiveness and sagittal parameters after ACDF, and those with the same position cervical kyphosis focal and spinal cord compression point have the best improvement in effectiveness and sagittal parameters.

Blautia Coccoides is a Newly Identified Bacterium Increased by Leucine Deprivation and has a Novel Function in Improving Metabolic Disorders.

Gut microbiota is linked to human metabolic diseases. The previous work showed that leucine deprivation improved metabolic dysfunction, but whether leucine deprivation alters certain specific species of bacterium that brings these benefits remains unclear. Here, this work finds that leucine deprivation alters gut microbiota composition, which is sufficient and necessary for the metabolic improvements induced by leucine deprivation. Among all the affected bacteria, B. coccoides is markedly increased in the feces of leucine-deprived mice. Moreover, gavage with B. coccoides improves insulin sensitivity and reduces body fat in high-fat diet (HFD) mice, and singly colonization of B. coccoides increases insulin sensitivity in gnotobiotic mice. The effects of B. coccoides are mediated by metabolizing tryptophan into indole-3-acetic acid (I3AA) that activates the aryl hydrocarbon receptor (AhR) in the liver. Finally, this work reveals that reduced fecal B. coccoides and I3AA levels are associated with the clinical metabolic syndrome. These findings suggest that B. coccoides is a newly identified bacterium increased by leucine deprivation, which improves metabolic disorders via metabolizing tryptophan into I3AA.

Endothelial peroxiredoxin-4 is indispensable for blood-brain barrier integrity and long-term functional recovery after ischemic stroke.

The endothelial lining of cerebral microvessels is damaged relatively early after cerebral ischemia/reperfusion (I/R) injury and mediates blood-brain barrier (BBB) disruption, neurovascular injury, and long-term neurological deficits. I/R induces BBB leakage within 1 h due to subtle structural alterations in endothelial cells (ECs), including reorganization of the actin cytoskeleton and subcellular redistribution of junctional proteins. Herein, we show that the protein peroxiredoxin-4 (Prx4) is an endogenous protectant against endothelial dysfunction and BBB damage in a murine I/R model. We observed a transient upregulation of Prx4 in brain ECs 6 h after I/R in wild-type (WT) mice, whereas tamoxifen-induced, selective knockout of Prx4 from endothelial cells (eKO) mice dramatically raised vulnerability to I/R. Specifically, eKO mice displayed more BBB damage than WT mice within 1 to 24 h after I/R and worse long-term neurological deficits and focal brain atrophy by 35 d. Conversely, endothelium-targeted transgenic (eTG) mice overexpressing Prx4 were resistant to I/R-induced early BBB damage and had better long-term functional outcomes. As demonstrated in cultures of human brain endothelial cells and in animal models of I/R, Prx4 suppresses actin polymerization and stress fiber formation in brain ECs, at least in part by inhibiting phosphorylation/activation of myosin light chain. The latter cascade prevents redistribution of junctional proteins and BBB leakage under conditions of Prx4 repletion. Prx4 also tempers microvascular inflammation and infiltration of destructive neutrophils and proinflammatory macrophages into the brain parenchyma after I/R. Thus, the evidence supports an indispensable role for endothelial Prx4 in safeguarding the BBB and promoting functional recovery after I/R brain injury.

Retracted: Rehmannia Radix Extract Relieves Bleomycin-Induced Pulmonary Fibrosis in Mice via Transforming Growth Factor ß1 (TGF-ß1).

The authors have requested retraction due to the identification of errors in the data. Reference: Xiaoming Hu, Dongzhe Zhu. Rehmannia Radix Extract Relieves Bleomycin-Induced Pulmonary Fibrosis in Mice via Transforming Growth Factor ß1 (TGF-ß1). Med Sci Monit, 2020; 26: e927240. DOI: 10.12659/MSM.927240.

Retracted: Alleviation of Inflammatory Response of Pulmonary Fibrosis in Acute Respiratory Distress Syndrome by Puerarin via Transforming Growth Factor (TGF-ß1).

The authors have requested retraction due to the identification of errors in the data. Reference: Xiaoming Hu, Xiaolan Huang. Alleviation of Inflammatory Response of Pulmonary Fibrosis in Acute Respiratory Distress Syndrome by Puerarin via Transforming Growth Factor (TGF-ß1). Med Sci Monit, 2019; 25: 6523-6531. DOI: 10.12659/MSM.915570.

Deciphering Oxygen-Independent Augmented Photodynamic Oncotherapy by Facilitating the Separation of Electron-Hole Pairs.

Developing Type-I photosensitizers provides an attractive approach to solve the dilemma of inadequate efficacy of photodynamic therapy (PDT) caused by the inherent oxygen consumption of traditional Type-II PDT and anoxic tumor microenvironment. The challenge for the exploration of Type-I PSs is to facilitate the electron transfer ability of photosensitization molecules for transforming oxygen or H2O to reactive oxygen species (ROS). Herein, we propose an electronic acceptor-triggered photoinduced electron transfer (a-PET) strategy promoting the separation of electron-hole pairs by marriage of two organic semiconducting molecules of a non-fullerene scaffold-based photosensitizer and a perylene diimide that significantly boost the Type-I PDT pathway to produce plentiful ROS, especially, inducing 3.5-fold and 2.5-fold amplification of hydroxyl (OH⋅) and superoxide (O2 -⋅) generation. Systematic mechanism exploration reveals that intermolecular electron transfer and intramolecular charge separation after photoirradiation generate a competent production of radical ion pairs that promote the Type-I PDT process by theoretical calculation and ultrafast femtosecond transient absorption (fs-TA) spectroscopy. By complementary tumor diagnosis with photoacoustic imaging and second near-infrared fluorescence imaging, this as-prepared nanoplatform exhibits fabulous photocytotoxicity in harsh hypoxic conditions and terrific cancer revoked abilities in living mice. We envision that this work will broaden the insight into high-efficiency Type-I PDT for cancer phototheranostics.

Research progress and challenges in stem cell therapy for diabetic foot: Bibliometric analysis and perspectives.

BACKGROUND: Stem cell therapy has shown great potential for treating diabetic foot (DF). AIM: To conduct a bibliometric analysis of studies on the use of stem cell therapy for DF over the past two decades, with the aim of depicting the current global research landscape, identifying the most influential research hotspots, and providing insights for future research directions. METHODS: We searched the Web of Science Core Collection database for all relevant studies on the use of stem cell therapy in DF. Bibliometric analysis was carried out using CiteSpace, VOSviewer, and R (4.3.1) to identify the most notable studies. RESULTS: A search was conducted to identify publications related to the use of stem cells for DF treatment. A total of 542 articles published from 2000 to 2023 were identified. The United States had published the most papers on this subject. In this field, Iran's Shahid Beheshti University Medical Sciences demonstrated the highest productivity. Furthermore, Dr. Bayat from the same university has been an outstanding researcher in this field. Stem Cell Research & Therapy is the journal with the highest number of publications in this field. The main keywords were "diabetic foot ulcers," "wound healing," and "angiogenesis." CONCLUSION: This study systematically illustrated the advances in the use of stem cell therapy to treat DF over the past 23 years. Current research findings suggested that the hotspots in this field include stem cell dressings, exosomes, wound healing, and adipose-derived stem cells. Future research should also focus on the clinical translation of stem cell therapies for DF.

J-Aggregation Strategy toward Potentiated NIR-II Fluorescence Bioimaging of Molecular Fluorophores.

Molecular fluorophores emitting in the second near-infrared (NIR-II, 1000-1700 nm) window with strong optical harvesting and high quantum yields hold great potential for in vivo deep-tissue bioimaging and high-resolution biosensing. Recently, J-aggregates are harnessed to engineer long-wavelength NIR-II emitters and show unique superiority in tumor detection, vessel mapping, surgical navigation, and phototheranostics due to their bathochromic-shifted optical bands in the required slip-stacked arrangement aggregation state. However, despite the preliminary progress of NIR-II J-aggregates and theoretical study of structure-property relationships, further paradigms of NIR-II J-aggregates remain scarce due to the lack of study on aggregated fluorophores with slip-stacked fashion. In this effort, how to utilize the specific molecular structure to form slip-stacked packing motifs with J-type aggregated exciton coupling is emphatically elucidated. First, several molecular regulating strategies to achieve NIR-II J-aggregates containing intermolecular interactions and external conditions are positively summarized and deeply analyzed. Then, the recent reports on J-aggregates for NIR-II bioimaging and theranostics are systematically summarized to provide a clear reference and direction for promoting the development of NIR-II organic fluorophores. Eventually, the prospective efforts on ameliorating and promoting NIR-II J-aggregates to further clinical practices are outlined.

Silencing of LINC00707 Alleviates Brain Injury by Targeting miR-30a-5p to Regulate Microglia Inflammation and Apoptosis.

The role of microglia in traumatic brain injury (TBI) has gained considerable attention. The present study aims to elucidate the potential mechanisms of Long intergenic non-protein coding RNA 707 (LINC00707) in TBI-induced microglia activation and inflammatory factor release. An in vivo model of rat TBI and in vitro microglia model was established using Controlled cortex injury (CCI) and lipopolysaccharide (LPS) stimulation. RT-qPCR to detect LINC00707 levels in rat cerebral cortex or cells. Modified Neurological Impairment Score (mNSS) and Morris Water Maze test was conducted to assess the neurological deficits and cognitive impairment. ELISA analysis of pro-inflammatory factors levels. CCK-8 and flow cytometry for cell viability and apoptosis levels. Dual-luciferase report and RIP assay to validate the targeting relationship between LINC00707 and miR-30a-5p. LINC00707 was elevated in the TBI rat cerebral cortex and LPS-induced microglia, while miR-30a-5p was noticeably decreased (P < 0.05). Increased mNSS, cognitive dysfunction, and brain edema in TBI rats were all prominently reversed by silencing of LINC00707, but this reversal was partially abrogated by decreasing miR-30a-5p (P < 0.05). Inhibition of LINC00707 suppressed the overproduction of inflammatory factors in TBI rats (P < 0.05). LPS decreased microglial cell viability, increased apoptosis, and promoted inflammatory overproduction than control, but the silencing of LINC00707 reversed its effect. Suppression of miR-30a-5p attenuated this reversal (P < 0.05). miR-30a-5p was the target miRNA of LINC00707. All in all, the results suggested that inhibiting LINC00707/miR-30a-5p axis could alleviate the progression of TBI by suppressing the inflammation and apoptosis of microglia cells.

Regulatory T lymphocytes in traumatic brain injury.

Traumatic brain injury (TBI) presents a significant global health challenge with no effective therapies developed to date. Regulatory T lymphocytes (Tregs) have recently emerged as a potential therapy due to their critical roles in maintaining immune homeostasis, reducing inflammation, and promoting brain repair. Following TBI, fluctuations in Treg populations and shifts in their functionality have been noted. However, the precise impact of Tregs on the pathophysiology of TBI remains unclear. In this review, we discuss recent advances in understanding the intricate roles of Tregs in TBI and other brain diseases. Increased knowledge about Tregs may facilitate their future application as an immunotherapy target for TBI treatment.

Intranasal mask for protecting the respiratory tract against viral aerosols.

The spread of many infectious diseases relies on aerosol transmission to the respiratory tract. Here we design an intranasal mask comprising a positively-charged thermosensitive hydrogel and cell-derived micro-sized vesicles with a specific viral receptor. We show that the positively charged hydrogel intercepts negatively charged viral aerosols, while the viral receptor on vesicles mediates the entrapment of viruses for inactivation. We demonstrate that when displaying matched viral receptors, the intranasal masks protect the nasal cavity and lung of mice from either severe acute respiratory syndrome coronavirus 2 or influenza A virus. With computerized tomography images of human nasal cavity, we further conduct computational fluid dynamics simulation and three-dimensional printing of an anatomically accurate human nasal cavity, which is connected to human lung organoids to generate a human respiratory tract model. Both simulative and experimental results support the suitability of intranasal masks in humans, as the likelihood of viral respiratory infections induced by different variant strains is dramatically reduced.

Effects of molybdenum supply on microbial diversity and mineral nutrient availability in the rhizosphere soil of broad bean (Vicia Faba L.).

Molybdenum application holds the potential to enhance agricultural productivity. However, the precise impact on soil microbial diversity and mineral nutrient availability remains uncertain. In this study, we collected rhizosphere soil samples from different growth stages of broad beans. By analyzing mineral element contents, soil phosphorus and zinc fractions, as well as fungal and bacterial diversity, we observed that Mo application resulted in a reduction of soil Citrate‒P and HCl‒P content. This reduction led to an increase in available P content at different stages. Moreover, Mo application elevated root P concentration, but concurrently impeded the translocation of P to the shoots. Mo application also decreased the soil Exc‒Zn (exchangeable Zn) content while increasing the Res‒Zn (residual Zn) content, ultimately causing a decrease in available Zn content at different stages. Consequently, the Zn concentration within broad beans correspondingly decreased. Mo application fostered an augmentation in fungal richness and Shannon indices at the branching and podding stages. The analysis of microbial co-occurrence networks indicated that Mo application bolstered positive connectivity among fungal taxa. Remarkably, Mo significantly increased the abundance of Chaetomium, Leucosporidium, and Thielavia fungi. Spearman correlation analysis demonstrated a significant positive correlation between fungal diversity and soil available P content, as well as a notable negative correlation with soil available Zn content. These findings suggest that Mo application may modify the availability of soil P and Zn by influencing fungal diversity in the rhizosphere of crop soil, ultimately impacting nutrient accumulation within the grains.

A systematic review on diagnosis and treatment of gastrointestinal diseases by magnetically controlled capsule endoscopy and artificial intelligence.

Background: Magnetically controlled capsule endoscopy (MCCE) is a non-invasive, painless, comfortable, and safe equipment to diagnose gastrointestinal diseases (GID), partially overcoming the shortcomings of conventional endoscopy and wireless capsule endoscopy (WCE). With advancements in technology, the main technical parameters of MCCE have continuously been improved, and MCCE has become more intelligent. Objectives: The aim of this systematic review was to summarize the research progress of MCCE and artificial intelligence (AI) in the diagnosis and treatment of GID. Data Sources and Methods: We conducted a systematic search of PubMed and EMBASE for published studies on GID detection of MCCE, physical factors related to MCCE imaging quality, the application of AI in aiding MCCE, and its additional functions. We synergistically reviewed the included studies, extracted relevant data, and made comparisons. Results: MCCE was confirmed to have the same performance as conventional gastroscopy and WCE in detecting common GID, while it lacks research in detecting early gastric cancer (EGC). The body position and cleanliness of the gastrointestinal tract are the main factors affecting imaging quality. The applications of AI in screening intestinal diseases have been comprehensive, while in the detection of common gastric diseases such as ulcers, it has been developed. MCCE can perform some additional functions, such as observations of drug behavior in the stomach and drug damage to the gastric mucosa. Furthermore, it can be improved to perform a biopsy. Conclusion: This comprehensive review showed that the MCCE technology has made great progress, but studies on GID detection and treatment by MCCE are in the primary stage. Further studies are required to confirm the performance of MCCE.

Measurement Technologies of Light Field Camera: An Overview.

Visual measurement methods are extensively used in various fields, such as aerospace, biomedicine, agricultural production, and social life, owing to their advantages of high speed, high accuracy, and non-contact. However, traditional camera-based measurement systems, relying on the pinhole imaging model, face challenges in achieving three-dimensional measurements using a single camera by one shot. Moreover, traditional visual systems struggle to meet the requirements of high precision, efficiency, and compact size simultaneously. With the development of light field theory, the light field camera has garnered significant attention as a novel measurement method. Due to its special structure, the light field camera enables high-precision three-dimensional measurements with a single camera through only one shot. This paper presents a comprehensive overview of light field camera measurement technologies, including the imaging principles, calibration methods, reconstruction algorithms, and measurement applications. Additionally, we explored future research directions and the potential application prospects of the light field camera.