Precede-Proceed Model-dominant Nursing Combined With Nutrition Support for Patients Discharged After Hepatobiliary Surgery With T Tube.

Context: Hepatobiliary disease requires surgical treatment and T-tube installment postoperatively, and discharged patients' usually still have a T tube. Little nursing care is available in China for patients after discharge, resulting in postdischarge complications. Also, the incidence of nutritional risk in patients with hepatobiliary surgery is high. Objective: The study aimed to investigate the benefits of a precede-proceed model-dominant nursing combined with nutritional support for patients discharged after hepatobiliary surgery with a T tube, so as to improve their prognoses and promote their rehabilitation. Design: The research team conducted a prospective, single-center, randomized controlled trial. Setting: The study took place at Wuhan No. 1 Hospital, Wuhan Hospital of Traditional Chinese and Western Medicine in Wuhan, Hubei, China. Participants: Participants were 120 patients discharged after hepatobiliary surgery at the hospital between June 2020 and June 2022. Interventions: The research team randomly divided participants into two groups using the random number table method, each with 60 participants: (1) an intervention group, which received precede-proceed model-dominant nursing combined with nutrition support and (2) a control group, which received routine care. Outcome Measures: At baseline and postintervention, the research team assessed: (1) nutritional status, (2) self-care agency, (3) compliance, (4) quality of life (QoL), (5) incidence of complications. Results: At baseline, no significant differences existed between the groups in nutritional status, self-care agency, QoL, or compliance (all P > .05). Postintervention compared to the control group, the intervention group's: (1) nutritional status, including albumin (P = .015), hemoglobin (P < .001), growth hormone (P < .001), BW (P = .047), BMI (P = .046), TST (P = .001), and MAMC (P = .016) were significantly higher and transferrin (P < .001) and NRS-2002 score (P < .001) were significantly lower; (2) self-care agency, including self-concept, self-responsibility, health knowledge, and self-nursing skills were significantly higher (all P < .001); (3) compliance scores, including observing the volume and color of bile correctly, clamping and opening the T tube properly, replacing the drainage bag correctly and in a timely manner, regularly disinfecting the skin around the drainage tube, keeping a balanced diet, adhering to medical regimens, exercising adequately were significantly higher (all P < .001); (4) QoL was significantly higher (P < .001); and (5) incidence of complications was significantly lower (P = .008). Conclusions: Precede-proceed model-dominant nursing combined with nutrition support can significantly improve nutritional status, self-care agency, and QoL and can significantly decrease the incidence of complications for patients discharged after hepatobiliary surgery with a T tube and is worthy of promotion in clinics.

Machine-Learning Models for Diagnosis of Rotator Cuff Tears in Osteoporosis Patients Based on Anteroposterior X-rays of the Shoulder Joint.

OBJECTIVE: This study aims to diagnose Rotator Cuff Tears (RCT) and classify the severity of RCT in patients with Osteoporosis (OP) through the analysis of shoulder joint anteroposterior (AP) X-ray-based localized proximal humeral bone mineral density (BMD) measurements and clinical information based on machine learning (ML) models. METHODS: A retrospective cohort of 89 patients was analyzed, including 63 with both OP and RCT (OPRCT) and 26 with OP only. The study analyzed a series of shoulder radiographs from April 2021 to April 2023. Grayscale values were measured after plotting ROIs based on AP X-rays of shoulder joint. Five kinds of ML models were developed and compared based on their performance in predicting the occurrence and severity of RCT from ROIs' greyscale values and clinical information (age, gender, advantage side, lumbar BMD, and acromion morphology (AM)). Further analysis using SHAP values illustrated the significant impact of selected features on model predictions. RESULTS: R1-6 had a positive correlation with BMD respectively. The nine variables, including greyscale R1-6, age, BMD, and AM, were used in the prediction models. The RF model was determined to be superior in effectively diagnosing RCT in OP patients, with high AUC scores of 0.998, 0.889, and 0.95 in the training, validation, and testing sets, respectively. SHAP values revealed that the most influential factors on the diagnostic outcomes were the grayscale values of all cancellous bones in ROIs. A column-line graph prediction model based on nine variables was constructed, and DCA curves indicated that RCT prediction in OP patients was favored based on this model. Furthermore, the RF model was also the most superior in predicting the types of RCT within the OPRCT group, with an accuracy of 86.364% and 73.684% in the training and test sets, respectively. SHAP values indicated that the most significant factor affecting the predictive outcomes was the AM, followed by the grayscale values of the greater tubercle, among others. CONCLUSIONS: ML models, particularly the RF algorithm, show significant promise in diagnosing RCT occurrence and severity in OP patients using conventional shoulder X-rays based on the nine variables. This method presents a cost-effective, accessible, and non-invasive diagnostic strategy that has the potential to substantially enhance the early detection and management of RCT in OP patient population.

Comparison of dual-plane micro-drop injection of botulinum toxin type A with two traditional methods for treating hypertrophic scars in the tension zone: A long-term clinical application study.

BACKGROUND: Patients with hypertrophic scarring tend to experience recurrence after treatment, which often occurs in areas of the body with high skin tension. AIMS: To evaluate better treatments aimed at reducing the risk of scar recurrence in areas of high skin tension. METHODS: Patients were randomly divided into the following three treatment groups: botulinum toxin type A (BTA) via dual-plane micro-drop injections, triamcinolone acetonide (TAC) suspension, and CO2 via fractional CO2 laser. Interventions were implemented in all three groups once a month for three consecutive sessions. After the final treatment, scarring was evaluated at 1, 3, 6, 12, and 24 months using the Patient and Observer Scar Assessment Scale (POSAS). RESULTS: The 3-month POSAS score for each scar indicator in the treatment groups was significantly lower than that in the preoperative groups (p < 0.001). The scar score in the TAC group decreased at 3 months and increased thereafter. For other groups, the scar score continually decreased at all time points according to the Patient Scar Assessment Scale. Based on the Observer Scar Assessment Scale, the scar score continuously decreased at all time points in the BTA group; in the TAC group, it decreased at 1 month and increased thereafter; and in the CO2 group, the scar score decreased at 3 months and subsequently stabilized. CONCLUSIONS: All three treatment methods were effective. However, the BTA group experienced a reduced risk of scar recurrence and maintained long-term treatment effects.

Analysis and validation of biomarkers of immune cell-related genes in postmenopausal osteoporosis: An observational study.

Postmenopausal osteoporosis (PMOP) is a common metabolic inflammatory disease. In conditions of estrogen deficiency, chronic activation of the immune system leads to a hypo-inflammatory phenotype and alterations in its cytokine and immune cell profile, although immune cells play an important role in the pathology of osteoporosis, studies on this have been rare. Therefore, it is important to investigate the role of immune cell-related genes in PMOP. PMOP-related datasets were downloaded from the Gene Expression Omnibus database. Immune cells scores between high bone mineral density (BMD) and low BMD samples were assessed based on the single sample gene set enrichment analysis method. Subsequently, weighted gene co-expression network analysis was performed to identify modules highly associated with immune cells and obtain module genes. Differential analysis between high BMD and low BMD was also performed to obtain differentially expressed genes. Module genes are intersected with differentially expressed genes to obtain candidate genes, and functional enrichment analysis was performed. Machine learning methods were used to filter out the signature genes. The receiver operating characteristic (ROC) curves of the signature genes and the nomogram were plotted to determine whether the signature genes can be used as a molecular marker. Gene set enrichment analysis was also performed to explore the potential mechanism of the signature genes. Finally, RNA expression of signature genes was validated in blood samples from PMOP patients and normal control by real-time quantitative polymerase chain reaction. Our study of PMOP patients identified differences in immune cells (activated dendritic cell, CD56 bright natural killer cell, Central memory CD4 T cell, Effector memory CD4 T cell, Mast cell, Natural killer T cell, T follicular helper cell, Type 1 T-helper cell, and Type 17 T-helper cell) between high and low BMD patients. We obtained a total of 73 candidate genes based on modular genes and differential genes, and obtained 5 signature genes by least absolute shrinkage and selection operator and random forest model screening. ROC, principal component analysis, and t-distributed stochastic neighbor embedding down scaling analysis revealed that the 5 signature genes had good discriminatory ability between high and low BMD samples. A logistic regression model was constructed based on 5 signature genes, and both ROC and column line plots indicated that the model accuracy and applicability were good. Five signature genes were found to be associated with proteasome, mitochondria, and lysosome by gene set enrichment analysis. The real-time quantitative polymerase chain reaction results showed that the expression of the signature genes was significantly different between the 2 groups. HIST1H2AG, PYGM, NCKAP1, POMP, and LYPLA1 might play key roles in PMOP and be served as the biomarkers of PMOP.

Catgut embedding in acupoints combined with repetitive transcranial magnetic stimulation for the treatment of postmenopausal osteoporosis: study protocol for a randomized clinical trial.

Background: To date, the clinical modulation for bone metabolism based on the neuro-bone mass regulation theory is still not popular. The stimulation of nerve systems to explore novel treatments for Postmenopausal osteoporosis (PMOP) is urgent and significant. Preliminary research results suggested that changes brain function and structure may play a crucial role in bone metabolism with PMOP. Thus, we set up a clinical trial to investigate the effect of the combination of repetitive transcranial magnetic stimulation (rTMS) and catgut embedding in acupoints (CEA) for PMOP and to elucidate the central mechanism of this neural stimulation in regulating bone metabolism. Method: This trial is a prospective and randomized controlled trial. 96 PMOP participants will be randomized in a 1:1:1 ratio into a CEA group, an rTMS group, or a combined one. Participants will receive CEA, rTMS, or combined therapy for 3 months with 8 weeks of follow-up. The primary outcomes will be the changes in Bone Mineral Density scores, total efficiency of Chinese Medicine Symptoms before and after treatment. Secondary outcomes include the McGill Pain Questionnaire Short-Form, Osteoporosis Symptom Score, Mini-Mental State Examination, and Beck Depression Inventory-II. The leptin, leptin receptor, and norepinephrine levels of peripheral blood must be measured before and after treatment. Adverse events that occur during the trial will be recorded. Discussion: CEA achieves brain-bone mass regulation through the bottom-up way of peripheral-central while rTMS achieves it through the top-down stimulation of central-peripheral. CEA combined with rTMS can stimulate the peripheral-central at the same time and promote peripheral bone mass formation. The combination of CEA and rTMS may play a coordinating, synergistic, and side-effect-reducing role, which is of great clinical significance in exploring better treatment options for PMOP.Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2300073863.

Sensorineural hearing loss and cognitive impairment: three hypotheses.

Sensorineural hearing loss (SNHL) is a category of hearing loss that often leads to difficulty in understanding speech and other sounds. Auditory system dysfunction, including deafness and auditory trauma, results in cognitive deficits via neuroplasticity. Cognitive impairment (CI) refers to an abnormality in the brain's higher intellectual processes related to learning, memory, thinking and judgment that can lead to severe learning and memory deficits. Studies have established a strong correlation between SNHL and CI, but it remains unclear how SNHL contributes to CI. The purpose of this article is to describe three hypotheses regarding this relationship, the mainstream cognitive load hypothesis, the co-morbidity hypothesis, and the sensory deprivation hypothesis, as well as the latest research progress related to each hypothesis.

Dubosiella newyorkensis modulates immune tolerance in colitis via the L-lysine-activated AhR-IDO1-Kyn pathway.

Commensal bacteria generate immensely diverse active metabolites to maintain gut homeostasis, however their fundamental role in establishing an immunotolerogenic microenvironment in the intestinal tract remains obscure. Here, we demonstrate that an understudied murine commensal bacterium, Dubosiella newyorkensis, and its human homologue Clostridium innocuum, have a probiotic immunomodulatory effect on dextran sulfate sodium-induced colitis using conventional, antibiotic-treated and germ-free mouse models. We identify an important role for the D. newyorkensis in rebalancing Treg/Th17 responses and ameliorating mucosal barrier injury by producing short-chain fatty acids, especially propionate and L-Lysine (Lys). We further show that Lys induces the immune tolerance ability of dendritic cells (DCs) by enhancing Trp catabolism towards the kynurenine (Kyn) pathway through activation of the metabolic enzyme indoleamine-2,3-dioxygenase 1 (IDO1) in an aryl hydrocarbon receptor (AhR)-dependent manner. This study identifies a previously unrecognized metabolic communication by which Lys-producing commensal bacteria exert their immunoregulatory capacity to establish a Treg-mediated immunosuppressive microenvironment by activating AhR-IDO1-Kyn metabolic circuitry in DCs. This metabolic circuit represents a potential therapeutic target for the treatment of inflammatory bowel diseases.

Exploring the Connectivity of Neurodegenerative Diseases: Microglia as the Center.

Degenerative diseases affect people's life and health and cause a severe social burden. Relevant mechanisms of microglia have been studied, aiming to control and reduce degenerative disease occurrence effectively. This review discussed the specific mechanisms underlying microglia in neurodegenerative diseases, age-related hearing loss, Alzheimer's disease, Parkinson's disease, and peripheral nervous system (PNS) degenerative diseases. It also reviewed the studies of microglia inhibitors (PLX3397/PLX5622) and activators (lipopolysaccharide), and suggested that reducing microglia can effectively curb the genesis and progression of degenerative diseases. Finally, microglial cells' anti-inflammatory and pro-inflammatory dual role was considered the critical communication point in central and peripheral degenerative diseases. Although it is difficult to describe the complex morphological structure of microglia in a unified manner, this does not prevent them from being a target for future treatment of neurodegenerative diseases.

[The objectification of ashi point diagnosis and treatment].

Ashi points play a significant role in the clinical localization and qualitative diagnosis of acupuncture, as well as in selecting acupoints along the meridians and applying tonifying or reducing techniques. This paper introduces the theoretical basis and existing technical methods of objectification of ashi point diagnosis and treatment. It proposes that using sensory quantitative testing to determine the temperature and tenderness thresholds of ashi points could help to identify the pathological characteristics of "cold" "heat" "deficiency" or "excess" of ashi points. In addition, the possibility of objectification of ashi point diagnosis-treatment plan is explored from three perspectives, precision of selection of ashi point therapy, objectification of effect evaluation of ashi point analgesia, and differentiation of the studies on ashi point analgesic mechanism, aiming to provide new research ideas for the modernization of traditional Chinese acupuncture.

Highly Efficient Light-Emitting Diodes Based on Self-Assembled Colloidal Quantum Wells.

Nanocrystal-based light-emitting diodes (Nc-LEDs) have immense potential for next-generation high-definition displays and lighting applications. They offer numerous advantages, such as low cost, high luminous efficiency, narrow emission, and long lifetime. However, the external quantum efficiency (EQE) of Nc-LEDs, typically employing isotropic nanocrystals, is limited by the out-coupling factor. Here efficient, bright, and long lifetime red Nc-LEDs based on anisotropic nanocrystals of colloidal quantum wells (CQWs) are demonstrated. Through modification of the substrate's surface properties and control of the interactions among CQWs, a self-assembled layer with an exceptionally high distribution of in-plane transitions dipole moment of 95%, resulting in an out-coupling factor of 37% is successfully spin-coated. The devices exhibit a remarkable peak EQE of 26.9%, accompanied by a maximum brightness of 55 754 cd m-2 and a long operational lifetime (T95 @100 cd m-2 ) over 15 000 h. These achievements represent a significant advancement compared to previous studies on Nc-LEDs incorporating anisotropic nanocrystals. The work is expected to provide a general self-assembly strategy for enhancing the light extraction efficiency of Nc-LEDs based on anisotropic nanocrystals.

Altered gut microbiota profile in patients with perimenopausal panic disorder.

Introduction: Females in the perimenopausal period are susceptible to mood disorders. Perimenopausal panic disorder (PPD) is characterized by repeated and unpredictable panic attacks during perimenopause, and it impacts the patient's physical and mental health and social function. Pharmacotherapy is limited in the clinic, and its pathological mechanism is unclear. Recent studies have demonstrated that gut microbiota is strongly linked to emotion; however, the relation between PPD and microbiota is limitedly known. Methods: This study aimed to discover specific microbiota in PPD patients and the intrinsic connection between them. Gut microbiota was analyzed in PPD patients (n = 40) and healthy controls (n = 40) by 16S rRNA sequencing. Results: The results showed reduced α-diversity (richness) in the gut microbiota of PPD patients. ß-diversity indicated that PPD and healthy controls had different intestinal microbiota compositions. At the genus level, 30 species of microbiota abundance had significantly different between the PPD and healthy controls. In addition, HAMA, PDSS, and PASS scales were collected in two groups. It was found that Bacteroides and Alistipes were positively correlated with PASS, PDSS, and HAMA. Discussion: Bacteroides and Alistipes dysbiosis dominate imbalanced microbiota in PPD patients. This microbial alteration may be a potential pathogenesis and physio-pathological feature of PPD. The distinct gut microbiota can be a potential diagnostic marker and a new therapeutic target for PPD.

Potential molecular mechanisms of Erlongjiaonang action in idiopathic sudden hearing loss: A network pharmacology and molecular docking analyses.

Background: Idiopathic sudden hearing loss (ISHL) is characterized by sudden unexplainable and unilateral hearing loss as a clinically emergent symptom. The use of the herb Erlongjiaonang (ELJN) in traditional Chinese medicine is known to effectively control and cure ISHL. This study explored the underlying molecular mechanisms using network pharmacology and molecular docking analyses. Method: The Traditional Chinese Medicine System Pharmacological database and the Swiss Target Prediction database were searched for the identification of ELJN constituents and potential gene targets, respectively, while ISHL-related gene abnormality was assessed using the Online Mendelian Inheritance in Man and Gene Card databases. The interaction of ELJN gene targets with ISHL genes was obtained after these databases were cross-screened, and a drug component-intersecting target network was constructed, and the gene ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction networks were analyzed. Cytoscape software tools were used to map the active components-crossover target-signaling pathway network and screened targets were then validated by establishing molecular docking with the corresponding components. Result: Erlongjiaonang contains 85 components and 250 corresponding gene targets, while ISHL has 714 disease-related targets, resulting in 66 cross-targets. The bioinformatical analyses revealed these 66 cross-targets, including isorhamnetin and formononetin on NOS3 expression, baicalein on AKT1 activity, and kaempferol and quercetin on NOS3 and AKT1 activity, as potential ELJN-induced anti-ISHL targets. Conclusion: This study uncovered potential ELJN gene targets and molecular signaling pathways in the control of ISHL, providing a molecular basis for further investigation of the anti-ISHL activity of ELJN.

Clinical Observation of Low-Temperature Plasma Ablation Combined with Drug Therapy in the Treatment of Fungal Keratitis.

Objective: To observe the efficacy and prognosis of low-temperature plasma ablation + drug therapy in the treatment of fungal corneal ulcers. Methods: The present paper presents a retrospective clinical study with a subject base of 34 eyes. Patients with a fungal corneal ulcer who visited the Affiliated Eye Hospital of Nanchang University between August 2019 and December 2021 were selected as the study participants. They were found to have highly reflective fungal hyphae in the corneal stroma layer via confocal microscope examination, which were revealed to be positive on etiology examination, with the ulcer and infiltration depths ≤1/2 of the corneal thickness. The efficacy and prognosis were observed after treatment with low-temperature plasma ablation + drug therapy. Results: A total of 34 cases (34 eyes) had clinical manifestations of corneal infiltration and corneal ulcer formation, with a corneal lesion diameter of 1.31-8.64 mm (average = 4.79 ± 2.03 mm). The average healing time of corneal ulcers was 6.2 ± 1.7 days. Among a total of 34 cases (34 eyes) in patients with fungal keratitis, the infection was controlled and the ulcers gradually healed after treatment with low-temperature plasma system + drug therapy in a total of 30 cases (30 eyes, 88%). A total of three cases (3 eyes, 9%) exhibited no clear improvement after the treatment, and the patients underwent conjunctival flap covering surgery. One case (one eye, 3%) exhibited no clear improvement after further treatment, with the patient experiencing corneal perforation and ultimately undergoing penetrating keratoplasty. Conclusion: Low-temperature plasma ablation + drug therapy can effectively control the progression of fungal keratitis infection, as well as significantly shorten the ulcer healing time, and is, therefore, an effective method.

BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility.

The transcription factor BTB and CNC homology 1(BACH1) has been linked to coronary artery disease risk by human genome-wide association studies, but little is known about the role of BACH1 in vascular smooth muscle cell (VSMC) phenotype switching and neointima formation following vascular injury. Therefore, this study aims to explore the role of BACH1 in vascular remodeling and its underlying mechanisms. BACH1 was highly expressed in human atherosclerotic plaques and has high transcriptional factor activity in VSMCs of human atherosclerotic arteries. VSMC-specific loss of Bach1 in mice inhibited the transformation of VSMC from contractile to synthetic phenotype and VSMC proliferation and attenuated the neointimal hyperplasia induced by wire injury. Mechanistically, BACH1 suppressed chromatin accessibility at the promoters of VSMC marker genes via recruiting histone methyltransferase G9a and cofactor YAP and maintaining the H3K9me2 state, thereby repressing VSMC marker genes expression in human aortic smooth muscle cells (HASMCs). BACH1-induced repression of VSMC marker genes was abolished by the silencing of G9a or YAP. Thus, these findings demonstrate a crucial regulatory role of BACH1 in VSMC phenotypic transition and vascular homeostasis and shed light on potential future protective vascular disease intervention via manipulation of BACH1.

Pyroptosis and degenerative diseases of the elderly.

Pyroptosis is a recently described mechanism of programmed cell death mediated by proteins of the gasdermin family. Widely recognized signaling cascades include the classical, non-classical, caspase-3-dependent gasdermin E and caspase-8-dependent gasdermin D pathways. Additional pyroptotic pathways have been subsequently reported. With the rising prevalence of advanced age, the role of pyroptosis in the degenerative diseases of the elderly has attracted increased research attention. This article reviews the primary mechanisms of pyroptosis and summarizes progress in the research of degenerative diseases of the elderly such as presbycusis, age-related macular degeneration, Alzheimer's disease, intervertebral disc degeneration, and osteoarthritis.

The Association between Allergic Rhinitis and COVID-19: A Systematic Review and Meta-Analysis.

Objective: Previous studies have yielded conflicting results regarding the association of coronavirus disease 2019 (COVID-19) with allergic rhinitis (AR). Data on AR prevalence in COVID-19 patients are limited. Consequently, whether AR is a harmful or protective factor for COVID-19 patients remains controversial. Therefore, we analyzed the relationship between COVID-19 and AR. Methods: We systematically searched PubMed, Embase, Cochrane, and Web of Science databases for studies published between January 1, 2020 and January 11, 2022. We included studies reporting the epidemiological and clinical characteristics of COVID-19 and its incidence in patients with AR. We excluded letters, case reports, literature review articles, non-English language article, and non-full-text articles. The raw data from these studies were pooled into a meta-analysis. Results: We analyzed the results of nine studies. The prevalence of AR in patients with COVID-19 was 0.13 (95% confidence interval [CI] 0.04-0.25), with an overall I 2 of 99.77%, P=0.24. COVID-19 patients with AR are less prone to severe disease (odds ratio [OR] = 0.79, 95% CI, 0.52-1.18, P=0.25) and hospitalization (OR = 0.23, 95%CI, 0.02-2.67, P ≤ 0.0001) than patients without AR. Conclusion: Our data suggest that allergic rhinitis is a protective factor in patients with COVID-19.

Plasmon-enhanced electrochemical oxidation of 4-(hydroxymethyl)benzoic acid.

Plasmon-mediated electrocatalysis based on plasmonic gold nanoparticles (Au NPs) has emerged as a promising approach to facilitate electrochemical reactions with the introduction of light to excite the plasmonic electrodes. We have investigated the electrochemical oxidation of 4-(hydroxymethyl)benzoic acid (4-HMBA) on gold (Au), nickel (Ni), and platinum (Pt) metal working electrodes in alkaline electrolytes. Au has the lowest onset potential for catalyzing the electrooxidation of 4-HMBA among the three metals in base, whereas Pt does not catalyze the electrooxidation of 4-HMBA under alkaline conditions, although it is conventionally a good electrocatalyst for alcohol oxidation. Both 4-carboxybenzaldehyde and terephthalic acid are detected as the products of electrochemical oxidation of 4-HMBA on the Au working electrode by high-performance liquid chromatography . The electrodeposited Au NPs on indium tin oxide (ITO)-coated glass is further utilized as the working electrode for the 4-HMBA electrooxidation. With its broad absorption in the visible and near-infrared range, we show that the Au NPs on the ITO electrode could enhance the electrochemical oxidation of 4-HMBA under green and red LED light illuminations (505 and 625 nm). A possible reaction mechanism is proposed for the electrochemical oxidation of 4-HMBA on Au working electrodes in an alkaline electrolyte.

Application and prospect of quasi-targeted metabolomics in age-related hearing loss.

Age-related hearing loss (ARHL) is a common sensory deficit in the elderly, which seriously affects physical and mental health. Therefore, understanding its underlying molecular mechanisms and taking interventions to treat ARHL are urgently needed. In our study, cochlea of 4-week-old C57BL/6 mice as the Youth group (n = 6) and 48-week-old cochlea as the Old group (n = 6) were subjected to quasi-targeted metabolomics analysis by Ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). In total, 208 differential metabolites were identified in 12 cochlea samples, which highlighted the following discriminant compounds: tryptophan, piperidine, methionine, L-arginine, histamine, serotonin, acetylcholine, and 4-aminobutyric acid. Differentially expressed metabolites were identified which were involved in KEGG pathways related to the digestion and absorption of oxidative stress associated amino acids, Synaptic vesicle cycle of serotonin, Pantothenate and CoA Biosynthesis. These findings are a first step toward elucidating the pathophysiological pathways involved in the etiology of ARHL and provide the possibility to further explore the mechanisms of ARHL using metabolomic analysis.

Tumor necrosis factor-α mediated inflammation versus apoptosis in age-related hearing loss.

An almost universal phenomenon occurring during aging is a state of chronic, low-grade, sterile inflammation. Inflammation is a crucial contributor to various age-related pathologies and natural processes in aging tissues. Tumor necrosis factor-α (TNF-α), a master regulator of the immune system, plays an important role in the propagation of inflammation. Recent research has found correlations between hearing loss and markers such as TNF-α. However, the intrinsic molecular mechanism by which TNF-α influences aging individuals' increased risk of hearing loss remains unclear. In this study, we found that TNF-α expression gradually increased with age in DBA/2J mice. We then used recombinant TNF-α to upregulate TNF-α levels in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and found that low concentrations of TNF-α could activate the nuclear factor kappa B (NF-κB) transcriptional response to mediate hair cell survival, while high concentrations of TNF-α could activate the Caspase-3 cascade to mediate hair cell apoptosis, which preliminarily confirmed that a TNF-α mediated signaling pathway plays an important role in the pathogenesis of age-related hearing loss.

Physiology-Inspired Multilayer Nanofibrous Membranes Modulating Endogenous Stem Cell Recruitment and Osteo-Differentiation for Staged Bone Regeneration.

Bone regeneration involves a cascade of sophisticated, multiple-staged cellular and molecular events, where early-phase stem cell recruitment mediated by chemokines and late-phase osteo-differentiation induced by pro-osteogenic factors play the crucial roles. Herein, enlightened by a bone physiological and regenerative mechanism, the multilayer nanofibrous membranes (PLLA@SDF-1α@MT01) consisting of PLLA/MT01 micro-sol electrospun nanofibers as intima and PLLA/PEG/SDF-1α electrospun nanofibers as adventitia are fabricated through micro-sol electrospinning and manual multi-layer stacking technologies. In vitro releasing profiles show that PLLA@SDF-1α@MT01 represents the rapid release of stromal cell-derived SDF-1α (SDF-1α) in the outer layers, while with long-term sustained release of MT01 in the inner layer. Owing to interconnected porosity like the natural bone extracellular matrix and improved hydrophilia, PLLA@SDF-1α@MT01 manifests good biocompatibility both in vitro and in vivo. Furthermore, PLLA@SDF-1α@MT01 can promote bone marrow mesenchymal stem cells (BMSCs) migration by amplifying the SDF-1α/CXCR4 axis and stimulating BMSCs osteo-differentiation via activating the MAPK pathway in vitro. PLLA@SDF-1α@MT01, with a programmed dual-delivery system, exhibits the synergetic promotion of bone regeneration and vascularization by emulating key characteristics of the staged bone repair in vivo. Overall, PLLA@SDF-1α@MT01 that mimics the endogenous cascades of bone regeneration can enrich the physiology-mimetic staged regenerative strategy and represent a promising tissue-engineered scaffold for the bone defect.