Polysaccharide-based hydrogels for cartilage regeneration.

Cartilage defect is one of the common tissue defect clinical diseases and may finally lead to osteoarthritis (OA) which threat patients' physical and psychological health. Polysaccharide is the main component of extracellular matrix (ECM) in cartilage tissue. In the past decades, polysaccharide-based hydrogels have shown great potential for cartilage regeneration considering unique qualities such as biocompatibility, enhanced cell proliferation, drug delivery, low toxicity, and many others. Structures such as chain length and chain branching make polysaccharides have different physical and chemical properties. In this review, cartilage diseases and current treatment options of polysaccharide-based hydrogels for cartilage defection repair were illustrated. We focus on how components and structures of recently developed materials affect the performance. The challenges and perspectives for polysaccharide-based hydrogels in cartilage repair and regeneration were also discussed in depth.

Remote care instruction via the WeChat platform for female patients receiving subcutaneous anticoagulation during the COVID-19 pandemic: a retrospective analysis.

Background: The purpose of this study was to estimate the effect of remote nursing guidance based on WeChat platform for female patients receiving subcutaneous anticoagulation during the COVID-19 epidemic. Methods: Retrospective analysis of clinical data, including demographic data and anticoagulation complications, of 126 female patients who received subcutaneous anticoagulation therapy and received remote nursing guidance using WeChat platform in our hospital from January 2022 to December 2022. The Anti-Clot Treatment Scale (ACTS) and the World Health Organization Quality of Life-BREF (WHOQOL-BREF) scale were used to evaluate patients' satisfaction with anticoagulation and quality of life at the beginning of anticoagulation, half a month after anticoagulation, and after three months of anticoagulation. Results: In total, 126 patients were involved in this study, all of them were female, 115 cases were natural pregnancy, 11 cases were assisted reproduction. This study included seven cases of lower extremity deep vein thrombosis, 100 cases of hypercoagulable state, 10 cases of antiphospholipid syndrome, and eight cases of protein S deficiency, one case of hyperhomocysteinemia. During the follow-up period, four patients (3.17%) had subcutaneous injection complications, including three cases of subcutaneous hemorrhage and one case of liquid leakage. A total of 123 patients had completed the planned anticoagulation therapy or were receiving anticoagulation therapy as planned, and three patients did not receive anticoagulation therapy as planned (zero cases lost contact, two cases changed treatment units, and one case refused treatment). ACTS score (55.03 ± 1.73) and WHOQOL-BREF score (62.18 ± 3.17) after three months of anticoagulation, ACTS score (54.18 ± 1.20) and WHOQOL-BREF score (60.37 ± 2.25) after half a month of anticoagulation was significantly higher than the ACTS score (47.81 ± 1.69) and WHOQOL-BREF score (55.25 ± 1.85) at the beginning of anticoagulation, and the difference was statistically significant (P value < 0.01). Conclusions: During the COVID-19 pandemic, remote nursing instruction via the WeChat platform for female patients receiving subcutaneous anticoagulation can increase anticoagulation compliance, satisfaction, and quality of life.

Research progress of biomarkers in evaluating the severity and prognostic value of severe pneumonia in children.

Pneumonia is a serious and common infectious disease in children. If not treated in time, it may develop into severe pneumonia. Severe pneumonia in children is mainly characterized by hypoxia and acidosis, often accompanied by various complications such as sepsis and multiple organ dysfunction. Severe pneumonia has a rapid onset and progression, and a high mortality rate. Biomarkers assist clinicians in the early diagnosis and treatment of patients by quickly and accurately identifying their conditions and prognostic risks. In this study, common clinical and novel biomarkers of severe pneumonia in children were reviewed, and the application value of biomarkers related to the severity and prognosis of severe pneumonia in children was evaluated to provide help for early identification and precise intervention by clinicians.

Sources of Allergens Detected Through Allergen-Specific Serum IgE Antibody Test in Children with Suspected Allergic Diseases in Central China.

Purpose: Although allergic diseases in children are on the rise, there has been no comprehensive investigation of the allergens affecting children with allergic diseases in central China. Therefore, we aimed to analyze the distribution of serum allergen species among children with allergic conditions in central China to inform the prevention, diagnosis, and treatment of childhood allergies. Patients and Methods: A total of 9213 children (5543 males with 2.88 ± 0.04 years old and 3670 females with 2.91 ± 0.05 years old) underwent allergen screening, and serum allergen-specific IgE (sIgE) antibodies were detected using an automated fluorescent enzyme immunoassay system. Results: Our findings revealed a total sIgE-positive rate (sIgE-PR) of 57.83%, with mixed food (42.10%), egg whites (30.83%), milk (28.97%), mixed dust mites (24.57%), and mixed molds (23.20%) being the most prevalent source of allergens. The sIgE-PR for common sources of allergens exhibited significant sex-based differences, with males having greater susceptibility than females (p<0.05). Dust mites were the primary source of inhaled allergens, whereas egg white was the predominant source of food allergens. Sources of food allergens were most dominant among infants (0-3 years old); sIgE-PRs for most source of food allergens decreased with age, whereas those for most source of inhaled allergens increased. The autumn sIgE-PRs for mixed molds, weed pollen combinations, and tree pollen combinations were significantly higher than those found in other seasons (p<0.05). Conclusion: Our findings suggest that sources of allergens profiles in children with allergies vary across age groups and seasons. Understanding these patterns can improve the effective prevention of childhood allergies.

Structural and Mutational Analyses of Trehalose Synthase from Deinococcus radiodurans Reveal the Interconversion of Maltose-Trehalose Mechanism.

Trehalose synthase (TreS) catalyzes the reversible interconversion of maltose to trehalose, playing a vital role in trehalose production. Understanding the catalytic mechanism of TreS is crucial for optimizing the enzyme activity and enhancing its suitability for industrial applications. Here, we report the crystal structures of both the wild type and the E324D mutant of Deinococcus radiodurans trehalose synthase in complex with the trehalose analogue, validoxylamine A. By employing structure-guided mutagenesis, we identified N253, E320, and E324 as crucial residues within the +1 subsite for isomerase activity. Based on these complex structures, we propose the catalytic mechanism underlying the reversible interconversion of maltose to trehalose. These findings significantly advance our comprehension of the reaction mechanism of TreS.

A sensitive fluorescence assay of serum dipeptidyl peptidase IV activity to predict the suitability of its inhibitors in patients with type 2 diabetes mellitus.

DPP-IV inhibitors, which are close to the natural hypoglycemic pathway of human physiology and have few side effects, have been extensively employed in the management of type 2 diabetes mellitus (T2DM). However, there are currently no specific blood indicators that can indicate or predict a patient's suitability for DPP-IV inhibitors. In this study, based on the self-developed high-specificity fluorescent substrate glycyl-prolyl-N-butyl-4-amino-1, 8-naphthimide (GP-BAN), a detection method of human serum DPP-IV activity was established and optimized. The method demonstrates a favorable lower limit of detection (LOD) at 0.32 ng/mL and a satisfactory lower limit of quantification (LOQ) of 1.12 ng/mL, and can be used for the detection of DPP-IV activity in trace serum (2 µL). In addition, Vitalliptin and Sitagliptin showed similar IC50 values when human recombinant DPP-IV and human serum were used as enzyme sources, and the intra-day and inter-day precision obtained by the microplate analyzer were less than 15 %. These results indicate that the microplate reader based detection technique has good accuracy, repeatability and reproducibility. A total of 700 volunteers were recruited, and 646 serum samples were tested for DPP-IV activity. The results showed that serum DPP-IV activity was higher in patients with T2DM than in controls (P < 0.01). However, the statistical data of family history of diabetes, gender and age of diabetic patients showed no statistical significance, and there was no contrast difference. The DPP-IV activity of serum in T2DM patients ranged from 2.4 µmol/min/L to 78.6 µmol/min/L, with a huge difference of up to 32-fold. These results suggest that it is necessary to test DPP-IV activity in patients with T2DM when taking DPP-IV inhibitors to determine the applicability of DPP-IV inhibitors in T2DM patients. These results suggest that it is necessary to detect the activity of DPP-IV in blood before taking DPP-IV inhibitors in patients with T2DM to judge the applicability of DPP-IV inhibitors in patients with T2DM.

Oral and oropharyngeal NUT carcinoma: a multicentre screening study of poorly differentiated oral cancer.

BACKGROUND AND AIMS: Nuclear protein testis (NUT) carcinoma (NC) is a rare and highly aggressive tumour characterised by chromosomal rearrangement of the nuclear protein testis family member 1 (NUTM1) gene, also known as the NUT gene. NC occurs mainly in the head and neck, mediastinum and lung. In general, primary NC in the oral cavity is extremely rare and reported sporadically. METHODS: A total of 111 formalin-fixed and paraffin-embedded specimens of poorly differentiated oral and oropharyngeal tumours were collected from 10 hospitals. NUT protein IHC staining was performed on these samples, and fluorescence in-situ hybridisation (FISH) and RNA sequencing detection were further carried out for NUT IHC-positive cases. RESULTS: The expression of NUT protein in tumour cells was detected in five cases (five of 111, 4.5%). The tumours in these cases were located in the oral floor, lip, base of the tongue, gingiva and hard palate. FISH detection results showed BRD4::NUT rearrangement in three patients and a non-BRD4::NUT rearrangement pattern in two patients. RNA sequencing results confirmed BRD4::NUT rearrangement in two cases. CONCLUSIONS: To our knowledge, this is the first and largest retrospective study of oral NC, and we found that NC is easily misdiagnosed as poorly differentiated oral squamous cell carcinoma (SCC) or poorly differentiated carcinoma. The morphology and immunophenotype of four NC cases were similar to SCC, and abrupt keratinisation was observed in three cases. Therefore, it is necessary to detect NUT protein for NC screening in oral malignant tumours with these morphologies, especially for young patients who are more likely to be misdiagnosed with other types of cancer.

The Poses for Equine Research Dataset (PFERD).

Studies of quadruped animal motion help us to identify diseases, understand behavior and unravel the mechanics behind gaits in animals. The horse is likely the best-studied animal in this aspect, but data capture is challenging and time-consuming. Computer vision techniques improve animal motion extraction, but the development relies on reference datasets, which are scarce, not open-access and often provide data from only a few anatomical landmarks. Addressing this data gap, we introduce PFERD, a video and 3D marker motion dataset from horses using a full-body set-up of densely placed over 100 skin-attached markers and synchronized videos from ten camera angles. Five horses of diverse conformations provide data for various motions from basic poses (eg. walking, trotting) to advanced motions (eg. rearing, kicking). We further express the 3D motions with current techniques and a 3D parameterized model, the hSMAL model, establishing a baseline for 3D horse markerless motion capture. PFERD enables advanced biomechanical studies and provides a resource of ground truth data for the methodological development of markerless motion capture.

Increased Expression of KNa1.2 Channel by MAPK Pathway Regulates Neuronal Activity Following Traumatic Brain Injury.

Recent studies have indicated that functional abnormalities in the KNa1.2 channel are linked to epileptic encephalopathies. However, the role of KNa1.2 channel in traumatic brain injury (TBI) remains limited. We collected brain tissue from the TBI mice and patients with post-traumatic epilepsy (PTE) to determine changes in KNa1.2 channel following TBI. We also investigated whether the MAPK pathway, which was activated by the released cytokines after injury, regulated KNa1.2 channel in in vitro. Finally, to elucidate the physiological significance of KNa1.2 channel in neuronal excitability, we utilized the null mutant-Kcnt2-/- mice and compared their behavior patterns, seizure susceptibility, and neuronal firing properties to wild type (WT) mice. TBI was induced in both Kcnt2-/- and WT mice to investigate any differences between the two groups under pathological condition. Our findings revealed that the expression of KNa1.2 channel was notably increased only during the acute phase following TBI, while no significant elevation was observed during the late phase. Furthermore, we identified the released cytokines and activated MAPK pathway in the neurons after TBI and confirmed that KNa1.2 channel was enhanced by the MAPK pathway via stimulation of TNF-α. Subsequently, compared to WT mice, neurons from Kcnt2-/- mice showed increased neuronal excitability and Kcnt2-/- mice displayed motor deficits and enhanced seizure susceptibility, which suggested that KNa1.2 channel may be neuroprotective. Therefore, this study suggests that enhanced KNa1.2 channel, facilitated by the inflammatory response, may exert a protective role in an acute phase of the TBI model.

The Application Value of CICARE Communication Mode Combined with Detailed Nursing on the Related Factors of Poor Prognosis of Patients After Gastric Cancer Resection.

Objective: To explore the independent risk factors for poor prognosis in patients with gastric cancer after resection and analyze the clinical application value of (connect-introduce-communicate-ask-respond-exit) CICARE communication mode combined with detailed nursing for such patients. Methods: 96 patients who underwent gastric cancer resection in our hospital from January 2019 to October 2019 were analyzed. They were divided into the good prognosis and poor prognosis group according to the postoperative adverse prognosis. The factors related to poor prognosis were analyzed by univariate and multivariate analysis. Another 106 patients who underwent gastric cancer resection from January 2020 to October 2021 were randomly divided into study and control group, with 53 patients in each group. The control group received routine nursing, and study group received CICARE communication mode combined with detailed nursing. Adverse mood changes were compared between the two groups before and after nursing. The changes of pain before surgery and 6 and 12 h after surgery were compared between the two groups as well as nursing satisfaction rate. Results: Univariate and multivariate results showed that body mass index (BMI) ≥ 28.00 kg/m2, length of hospital stay≥10 d, and preoperative complications≥2 were independent risk factors for poor prognosis after gastric cancer resection (P < .05). Compared with the control group, the incidence of postoperative adverse reactions in the study group was significantly reduced (P < .05). The bad mood of the two groups was alleviated compared with that before nursing, but the study group was significantly better than control (P < .05). The pain degree in both groups decreased with time, the study group was significantly lower than that in control (P < .05). Nursing satisfaction of the study group was significantly higher than that of control (P < .05). Conclusion: BMI ≥ 28.00 kg/m2, length of hospital stay≥10 d, and preoperative complications ≥ 2 types can cause postoperative adverse reactions in patients with gastric cancer resection. CICARE detailed nursing based on the above risk factors can effectively reduce postoperative complications and relieve postoperative pain and adverse emotions of patients, which has high clinical application value.

Licochalcone A Derivatives as Selective Dipeptidyl Peptidase 4 Inhibitors with Anti-Inflammatory Effects.

A set of 22 analogs of licochalcone A was designed and synthesized to explore their potentials as dipeptidyl peptidase 4 (DPP4) inhibitors with anti-inflammatory effects. The anti-DPP4 effects of these analogs were evaluated using the fluorescent substrate Gly-Pro-N-butyl-4-amino-1,8-naphthalimide (GP-BAN). The nitro-substituted analogue 27 exhibited the most potent activity (Ki = 0.96 µM). A structure-activity relationship investigation revealed that 4-hydroxyl and 5-chloro substituents are essential for DPP4 inhibition, while the 3'-nitro substituent improved both DPP4 inhibition and microsomal stability. Furthermore, compound 27 demonstrated good selectivity for DPP4 over other proteases, including dipeptidyl peptidase 9 (DPP9), thrombin, prolyl endopeptidase (PREP), and fibroblast activation protein (FAP). The cytotoxic effect of 27 was evaluated in cancer cell lines HepG-2 and Caco-2 and in somatic RAW264.7 cells and RPTECs. Compound 27 showed no toxicity to normal cells and weak toxicity to cancer cells. In a living cell imaging assay, 27 blocked the dipeptidase activity of DPP4 in both Caco-2 and HepG-2 cells. This compound also dose-dependently suppressed the expression levels of the chemokines tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß).

Discovery of anthraquinones as DPP-IV inhibitors: Structure-activity relationships and inhibitory mechanism.

Dipeptidyl peptidase IV (DPP-IV) is an integrated type II transmembrane protein that reduces endogenous insulin contents and increases plasma glucose levels by hydrolyzing glucagon-like peptide-1 (GLP-1). Inhibition of DPP-IV regulates and maintains glucose homeostasis, making it an attractive drug target for the treatment of diabetes II. Natural compounds have tremendous potential to regulate glucose metabolism. In this study, we examined the DPP-IV inhibitory activity of a series of natural anthraquinones and synthetic structural analogues on DPP-IV using fluorescence-based biochemical assays. The inhibitory efficiency differed among anthraquinone compounds with different structures. Alizarin (7), aloe emodin (11), emodin (13) emerged the outstanding inhibitory potential for DPP-IV with IC50 values lower than 5 µM. To clarifying the inhibitory mechanism, inhibitory kinetics were performed, which showed that alizarin red S (8) and 13 were effective non-competitive inhibitors of DPP-IV, while alizarin complexone (9), rhein (12), and anthraquinone-2-carboxylic acid (23) were mixed inhibitors. Emodin was determined as inhibitor with the strongest DPP-IV-binding affinity determined via molecular docking. Structure-activity relationship (SAR) demonstrated that hydroxyl group at C-1 and C-8 sites and hydroxyl, hydroxymethyl or carboxyl group at the C-2 or C-3 site were very essential for DPP-IV inhibition, replacement of hydroxyl group with amino group at C-1 could led to an increase of the inhibitory potential. Further fluorescence imaging showed that both compounds 7 and 13 significantly inhibited DPP-IV activity in RTPEC cells. Overall, the results indicated that anthraquinones would be a natural functional ingredient for inhibiting DPP-IV and provided new ideas for searching and developing potential antidiabetic compounds.

Proposal and validation of a new classification for trochanteric fractures based on medial buttress and lateral cortical integrity.

Background: Trochanteric fractures usually require surgical treatment. The currently used classification system, such as AO classification, cannot cover all variant types, and is poor in reliability, causing confusion in surgical decision making. This study describes a simple, well-covered, re-liable, accurate, and clinically useful classification. Methods: We retrospectively reviewed the records of 907 patients with trochanteric fractures treated by us from 1,999 to 2019 and proposed a new classification according to radiographs. Then, 50 records randomly selected in proportion were examined by 10 observers (5 experienced and 5 inexperienced) independently according to AO and the new classification. After a 2-week interval, repeat evaluation was completed. The Kappa coefficient was used to investigate the intra-observer reliability, inter-observer reliability and the agreement between the observers and the "reference standard". Results: The new classification system includes 12 types composed of 3 medial groups and 4 lateral groups. According to the medial buttress, the fractures are divided into group I (intact lesser trochanter, adequate but-tress), group II (incomplete lesser trochanter, effective cortical buttress after reduction) and group III (huge defect of the medial cortex). According to the penetration region of the lateral fracture line, the fractures are divided into group A (intact lateral cortex), group B (incomplete lateral cortex), group C (subtrochanteric fractures) and group D (multiple lateral fracture lines). All of the included cases can be classified according to the new classification, of which 34 (3.75%) cases are unclassifiable by the AO classification. Intra-observer: The experienced achieved substantial agreement using both AO [k = 0.61 (95% confidence interval 0.46-0.76)] and new classification [k = 0.65 (0.55-0.76)]. The inexperienced reached moderate agreement using both AO [k = 0.48 (0.33-0.62)] and new classification [k = 0.60 (0.50-0.71)]. Inter-observer: The overall reliabilities for AO [k = 0.51 (0.49-0.53)] and for new classification [k = 0.57 (0.55-0.58)] were both moderate. The agreement between the experienced and the reference standard according to AO [k = 0.61 (0.49-0.74)] and new classification [k = 0.63 (0.54-0.72)] were both substantial. The agreement between the inexperienced and the reference standard according to AO [k = 0.48 (0.45-0.50)] and the new classification [k = 0.48 (0.41-0.54)] were both moderate. Conclusion: Compared with AO classification, our new classification is better in coverage, reliability and accuracy, and has the feasibility of clinical verification and promotion.

Performance comparison of three scaling algorithms in NMR-based metabolomics analysis.

Unit variance (UV) scaling, mean centering (CTR) scaling, and Pareto (Par) scaling are three commonly used algorithms in the preprocessing of metabolomics data. Based on our NMR-based metabolomics studies, we found that the clustering identification performances of these three scaling methods were dramatically different as tested by the spectra data of 48 young athletes' urine samples, spleen tissue (from mice), serum (from mice), and cell (from Staphylococcus aureus) samples. Our data suggested that for the extraction of clustering information, UV scaling could serve as a robust approach for NMR metabolomics data for the identification of clustering analysis even with the existence of technical errors. However, for the purpose of discriminative metabolite identification, UV scaling, CTR scaling, and Par scaling could equally extract discriminative metabolites efficiently based on the coefficient values. Based on the data presented in this study, we propose an optimal working pipeline for the selection of scaling algorithms in NMR-based metabolomics analysis, which has the potential to serve as guidance for junior researchers working in the NMR-based metabolomics research field.

Oxidative stress, dysfunctional energy metabolism, and destabilizing neurotransmitters altered the cerebral metabolic profile in a rat model of simulated heliox saturation diving to 4.0 MPa.

The main objective of the present study was to determine metabolic profile changes in the brains of rats after simulated heliox saturated diving (HSD) to 400 meters of sea water compared to the blank controls. Alterations in the polar metabolome in the rat brain due to HSD were investigated in cortex, hippocampus, and striatum tissue samples by applying an NMR-based metabolomic approach coupled with biochemical detection in the cortex. The reduction in glutathione and taurine levels may hypothetically boost antioxidant defenses during saturation diving, which was also proven by the increased malondialdehyde level, the decreased superoxide dismutase, and the decreased glutathione peroxidase in the cortex. The concomitant decrease in aerobic metabolic pathways and anaerobic metabolic pathways comprised downregulated energy metabolism, which was also proven by the biochemical quantification of the metabolic enzymes Na-K ATPase and LDH in cerebral cortex tissue. The significant metabolic abnormalities of amino acid neurotransmitters, such as GABA, glycine, and aspartate, decreased aromatic amino acids, including tyrosine and phenylalanine, both of which are involved in the metabolism of dopamine and noradrenaline, which are downregulated in the cortex. Particularly, a decline in the level of N-acetyl aspartate is associated with neuronal damage. In summary, hyperbaric decompression of a 400 msw HSD affected the brain metabolome in a rat model, potentially including a broad range of disturbing amino acid homeostasis, metabolites related to oxidative stress and energy metabolism, and destabilizing neurotransmitter components. These disturbances may contribute to the neurochemical and neurological phenotypes of HSD.

Anti-Ferroptotic Effects of bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicles Loaded with Ferrostatin-1 in Cerebral ischemia-reperfusion Injury Associate with the GPX4/COX-2 Axis.

Accumulating evidence of the critical role of Ferrostatin-1 (Fer-1, ferroptosis inhibitor) in cerebral ischemia has intrigued us to explore the molecular mechanistic actions of Fer-1 delivery by bone marrow mesenchymal stem cells-derived extracellular vesicles (MSCs-EVs) in cerebral ischemia-reperfusion (I/R) injury. In vivo middle cerebral artery occlusion (MCAO) in mice and in vitro oxygen-glucose deprivation/reperfusion (OGD/R) in hippocampal neurons were developed to simulate cerebral I/R injury. After Fer-1 was confirmed to be successfully delivered by MSCs-EVs to neurons, we found that MSCs-EVs loaded with Fer-1 (MSCs-EVs/Fer-1) reduced neuron apoptosis and enhanced viability, along with curtailed inflammation and ferroptosis. The regulation of Fer-1 on GPX4/COX2 axis was predicted by bioinformatics study and validated by functional experiments. The in vivo experiments further confirmed that MSCs-EVs/Fer-1 ameliorated cerebral I/R injury in mice. Furthermore, poor expression of GPX4 and high expression of COX-2 were witnessed in cerebral I/R injury models. MSCs-EVs/Fer-1 exerted its protective effects against cerebral I/R injury by upregulating GPX4 expression and inhibiting COX-2 expression. Taken together, our study indicates that MSCs-EVs/Fer-1 may be an attractive therapeutic target for the treatment of cerebral I/R injury due to its anti-ferroptotic properties.

Janus mucosal dressing with a tough and adhesive hydrogel based on synergistic effects of gelatin, polydopamine, and nano-clay.

There are many problems and challenges related to the treatment of highly prevalent oral mucosal diseases and oral drug delivery because of a large amount of saliva present in the oral cavity, the accompanying oral movements, and unconscious swallowing in the mouth. Therefore, an ideal oral dressing should possess stable adhesion and superior tough strength in the oral cavity. However, this fundamental requirement greatly limits the use of synthetic adhesive dressings for oral dressings. Here, we developed a mussel-inspired Janus gelatin-polydopamine-nano-clay (GPC) hydrogel with controlled adhesion and toughness through the synergistic physical and chemical interaction of gelatin (Gel), nano-clay, and dopamine (DA). The hydrogel not only exhibits strong wet adhesion force (63 kPa) but also has high toughness (1026 ± 100 J m-3). Interfacial adhesion of hydrogels is achieved by modulating the interaction of catechol groups of the hydrogel with specific functional groups (e.g., NH2, SH, OH, and COOH) on the tissue surface. The matrix dissipation of the hydrogel is regulated by physical crosslinking of gelatin, chemical crosslinking of gelatin with polydopamine (Michael addition and Schiff base formation), and nano-clay-induced constraint of the molecular chain. In addition, the GPC hydrogel shows high cell affinity and favors cell adhesion and proliferation. The hydrogel's instant and strong mucoadhesive properties provide a long-lasting therapeutic effect of the drug, thereby enhancing the healing of oral ulcers. Therefore, mussel-inspired wet-adhesion Janus GPC hydrogels can be used as a platform for mucosal dressing and drug delivery systems. STATEMENT OF SIGNIFICANCE: It is a great challenge to treat oral mucosal diseases due to the large amount of saliva present in the oral cavity, the accompanying oral movements, unconscious swallowing, and flushing of drugs in the mouth. To overcome the significant limitations of clinical bioadhesives, such as weakness, toxicity, and poor usage, in the present study, we developed a simple method through the synergistic effects of gelatin, polydopamine, and nano-clay to prepare an optimal mucosal dressing (Janus GPC) that integrates Janus, adhesion, toughness, and drug release property. It fits effectively in the mouth, resists saliva flushing and oral movements, provides oral drug delivery, and reduces patient discomfort. The Janus GPC adhesive hydrogels have great commercial potential to support further the development of innovative therapies for oral mucosal diseases.

IL-1ß-Triggered Long Non-coding RNA CHRF Induces Non-Small Cell Lung Cancer by Modulating the microRNA-489/Myd88 Axis.

Background: Long noncoding RNAs (LncRNAs) possess crucial roles in carcinogenesis. The current study aims to evaluate the effects of interleukin-1ß (IL-1ß)-mediated lncRNA cardiac hypertrophy-related factor (CHRF)/microRNA-489 (miR-489)/myeloid differentiation factor 88 (Myd88) on non-small-cell lung cancer (NSCLC). Methods: Initially, the expression of IL-1ß and lncRNA CHRF in NSCLC cells and tissues was determined, respectively. H460 cell line with highest lncRNA CHRF expression was selected for in vitro experimentations. Afterward, the interaction among lncRNA CHRF, miR-489, and Myd88 was verified with their significance in cell functions and tumorigenicity and lung metastasis analyzed following. Results: IL-1ß and lncRNA CHRF was remarkably upregulated in NSCLC. IL-1ß was able to elevate lncRNA CHRF expression. Additionally, lncRNA CHRF targeted miR-489 and miR-489 targeted Myd88. Moreover, functional assay results suggested that under IL-1ß treatment, lncRNA CHRF induced NSCLC cell malignant properties and tumorigenicity and lung metastasis through modulation of miR-489/Myd88 axis. Conclusion: Taken together, our findings revealed that IL-1ß-induced elevation of lncRNA CHRF aggravated NSCLC through modulation of miR-489/Myd88 axis, which provides a novel direction for NSCLC therapy development.

An electroencephalography-based human-machine interface combined with contralateral C7 transfer in the treatment of brachial plexus injury.

Transferring the contralateral C7 nerve root to the median or radial nerve has become an important means of repairing brachial plexus nerve injury. However, outcomes have been disappointing. Electroencephalography (EEG)-based human-machine interfaces have achieved promising results in promoting neurological recovery by controlling a distal exoskeleton to perform functional limb exercises early after nerve injury, which maintains target muscle activity and promotes the neurological rehabilitation effect. This review summarizes the progress of research in EEG-based human-machine interface combined with contralateral C7 transfer repair of brachial plexus nerve injury. Nerve transfer may result in loss of nerve function in the donor area, so only nerves with minimal impact on the donor area, such as the C7 nerve, should be selected as the donor. Single tendon transfer does not fully restore optimal joint function, so multiple functions often need to be reestablished simultaneously. Compared with traditional manual rehabilitation, EEG-based human-machine interfaces have the potential to maximize patient initiative and promote nerve regeneration and cortical remodeling, which facilitates neurological recovery. In the early stages of brachial plexus injury treatment, the use of an EEG-based human-machine interface combined with contralateral C7 transfer can facilitate postoperative neurological recovery by making full use of the brain's computational capabilities and actively controlling functional exercise with the aid of external machinery. It can also prevent disuse atrophy of muscles and target organs and maintain neuromuscular junction effectiveness. Promoting cortical remodeling is also particularly important for neurological recovery after contralateral C7 transfer. Future studies are needed to investigate the mechanism by which early movement delays neuromuscular junction damage and promotes cortical remodeling. Understanding this mechanism should help guide the development of neurological rehabilitation strategies for patients with brachial plexus injury.

Polydopamine-modified chitin conduits with sustained release of bioactive peptides enhance peripheral nerve regeneration in rats.

The introduction of neurotrophic factors into injured peripheral nerve sites is beneficial to peripheral nerve regeneration. However, neurotrophic factors are rapidly degraded in vivo and obstruct axonal regeneration when used at a supraphysiological dose, which limits their clinical benefits. Bioactive mimetic peptides have been developed to be used in place of neurotrophic factors because they have a similar mode of action to the original growth factors and can activate the equivalent receptors but have simplified sequences and structures. In this study, we created polydopamine-modified chitin conduits loaded with brain-derived neurotrophic factor mimetic peptides and vascular endothelial growth factor mimetic peptides (Chi/PDA-Ps). We found that the Chi/PDA-Ps conduits were less cytotoxic in vitro than chitin conduits alone and provided sustained release of functional peptides. In this study, we evaluated the biocompatibility of the Chi/PDA-Ps conduits. Brain-derived neurotrophic factor mimetic peptide and vascular endothelial growth factor mimetic peptide synergistically promoted proliferation of Schwann cells and secretion of neurotrophic factors by Schwann cells and attachment and migration of endothelial cells in vitro. The Chi/PDA-Ps conduits were used to bridge a 2 mm gap between the nerve stumps in rat models of sciatic nerve injury. We found that the application of Chi/PDA-Ps conduits could improve the motor function of rats and reduce gastrocnemius atrophy. The electrophysiological results and the microstructure of regenerative nerves showed that the nerve conduction function and remyelination was further restored. These findings suggest that the Chi/PDA-Ps conduits have great potential in peripheral nerve injury repair.