Lateralized response of skull bone marrow via osteopontin signaling in mice after ischemia reperfusion.

Skull bone marrow is thought to be an immune tissue closely associated with the central nervous system (CNS). Recent studies have focused on the role of skull bone marrow in central nervous system disorders. In this study, we performed single-cell RNA sequencing on ipsilateral and contralateral skull bone marrow cells after experimental stroke and then performed flow cytometry and analysis of cytokine expression. Skull marrow showed lateralization in response to stroke. Lateralization is demonstrated primarily by the proliferation and differentiation of myeloid and lymphoid lineage cells in the skull bone marrow adjacent to the ischemic region, with an increased proportion of neutrophils compared to monocytes. Analysis of chemokines in the skull revealed marked differences in chemotactic signals between the ipsilateral and contralateral skull, whereas sympathetic signals innervating the skull did not affect cranial bone marrow lateralization. Osteopontin (OPN) is involved in region-specific activation of the skull marrow that promotes inflammation in the meninges, and inhibition of OPN expression improves neurological function.

The Prognostic Value of ADAMTS8 and Its Role as a Tumor Suppressor in Breast Cancer.

A disintegrin-like and metalloprotease with therombospondin type1 motif 8 (ADAMTS8) plays an important role in many malignancies. However, the clinical and biological significance of ADAMTS8 in breast cancer remain unknown. In this study, the clinical data from 1066 breast cancer patients were analyzed by The Cancer Genome Atlas (TCGA) database, and were analyzed using the correlation between ADAMTS8 expression and the clinicopathological features and prognoses. The CCK-8 assay, clone formation assay, flow cytometry and Transwell assay were used to characterize the effects of ADAMTS8 on proliferation, migration and invasion of breast cancer cells. Gene set enrichment analysis (GSEA) and western blotting were used to identify the potential molecular mechanism on how ADAMTS8 exert its biological function. ADAMTS8 overexpression correlated longer overall survival (OS) and progression-free survival (PFS). ADAMTS8 was considered as an independent prognostic factor for OS. ADAMTS8 overexpression inhibited breast cancer cell proliferation, migration and invasion in vitro, and induced G2/M cell cycle arrest. ADAMTS8 was also involved in cell cycle regulation and was associated with the EGFR/Akt signaling pathway. ADAMTS8 knockdown showed the reverse effect. Together, the results showed that ADAMTS8 functioned as a tumor suppressor gene (TGS) and could be a prognostic biomarker for breast cancer.

Pharmacological Modulations of Nrf2 and Therapeutic Implications in Aneurysmal Subarachnoid Hemorrhage.

An aneurysmal subarachnoid hemorrhage (aSAH) is a subtype of stroke with high morbidity and mortality. The main causes of a poor prognosis include early brain injury (EBI) and delayed vasospasm, both of which play a significant role in the pathophysiological process. As an important mechanism of EBI and delayed vasospasm, oxidative stress plays an important role in the pathogenesis of aSAH by producing reactive oxygen species (ROS) through the mitochondria, hemoglobin, or enzymatic pathways in the early stages of aSAH. As a result, antioxidant therapy, which primarily targets the Nrf2-related pathway, can be employed as a potential strategy for treating aSAH. In the early stages of aSAH development, increasing the expression of antioxidant enzymes and detoxifying enzymes can relieve oxidative stress, reduce brain damage, and improve prognosis. Herein, the regulatory mechanisms of Nrf2 and related pharmacological compounds are reviewed, and Nrf2-targeted drugs are proposed as potential treatments for aSAH.

BTNL9 is frequently downregulated and inhibits proliferation and metastasis via the P53/CDC25C and P53/GADD45 pathways in breast cancer.

Breast cancer (BC) threatens the life and health of women worldwide because of its high morbidity and mortality. The present study aimed to explore the biological functions and potential mechanism of BTNL9 in BC. RNA sequence and clinical data extracted from the Kaplan-Meier plotter database and The Cancer Genome Atlas (TCGA) were utilized to analyze the relationship between the expression level of BTNL9 in BC tissues and clinicopathological features and the effects of BTNL9 expression on the prognosis of BC. The diagnostic efficacy of BTNL9 expression was estimated by receiver operating characteristic (ROC) curve analysis. The mRNA and protein expression levels of BTNL9 in BC cell lines and in BC tissue were determined by quantitative real-time PCR (qPCR) and western blotting, respectively. The functions of BTNL9 were measured by colony formation, CCK-8, Transwell, flow cytometry and EdU assays. Western blotting analysis was also performed to explore the latent mechanism of BTNL9. The results showed that the expression of BTNL9 declined in BC tissues and cell lines. Low expression of BTNL9 was significantly associated with early progression of T stage, relapse-free survival (RFS), and poor overall survival (OS). Ectopic expression of BTNL9 inhibited cell proliferation, colony formation and metastasis and induced apoptosis in BC, while knockdown of BTNL9 had the opposite result. Furthermore, BTNL9 blocked BC cells in the G2/M phase via the P53/CDC25C and P53/GADD45 pathways. Our results suggest that BTNL9 may play a tumor-suppressive role in BC and has the potency to become a new biomarker for early BC diagnosis.

Adherence to oxidative balance score is inversely associated with the prevalence of stroke: results from National Health and Nutrition Examination Survey 1999-2018.

Introduction: The relationship between oxidative balance score (OBS), an emerging integrative metric for assessing individual redox homeostasis, and the prevalence of stroke in the general population remains unknown. We aimed to explore these relationships in the National Health and Nutrition Examination Survey (NHANES). We investigated the relationship between the oxidative balance score (OBS) and stroke prevalence using NHANES data from 1999-2018. Methods: We included eligible individuals from NHANES 1999-2018. OBS calculations were based on previously validated methods, and stroke diagnoses were based on self-reports in questionnaires. Multivariable logistic regression analyses were used to examine the independent associations of overall, dietary, and lifestyle OBS with stroke prevalence. In addition, restricted cubic spline (RCS), stratified analysis, and sensitivity analysis were used. Results: We included 25,258 participants aged 20-85 years, in which the prevalence of stroke was 2.66%. After adjusting for all confounders, overall and dietary OBS, but not lifestyle OBS, were inversely associated with the prevalence of stroke [odds ratios and 95% confidence intervals of 0.97 (0.96, 0.99) and 0.98 (0.96, 0.99) for overall and dietary OBS, respectively, both p < 0.05]. In addition, there was a dose-response relationship between overall and dietary OBS and stroke prevalence. The RCS showed that these relationships were linear. Stratified analyses indicated that socioeconomic status (SES) significantly influenced the relationship between all OBS and stroke prevalence. Conclusion: Dietary OBS, but not lifestyle OBS, had an inverse relationship with the prevalence of stroke in the general population. SES significantly influenced the protective effect of OBS against stroke. These findings emphasize the importance of integrated antioxidant properties from diet for stroke prevention.

Hierarchical Spatial Confinement Unlocking the Storage Limit of MoS2 for Flexible High-Energy Supercapacitors.

Molybdenum sulfide (MoS2) is a promising electrode material for supercapacitors; however, its limited Mo/S edge sites and intrinsic inert basal plane give rise to sluggish active electronic states, thus constraining its electrochemical performance. Here we propose a hierarchical confinement strategy to develop ethylene molecule (EG)-intercalated Co-doped sulfur-deficient MoS2 (Co-EG/SV-MoS2) for efficient and durable K-ion storage. Theoretical analyses suggest that the intercalation-confined EG and lattice-confined Co can enhance the interfacial K-ion storage capacity while reducing the K-ion diffusion barrier. Experimentally, the intercalated EG molecules with mildly reducing properties induced the creation of sulfur vacancies, expanded the interlayer spacing, regulated the 2H-1T phase transition, and strengthened the structural grafting between layers, thereby facilitating ion diffusion and ensuring structural durability. Moreover, the Co dopants occupying the initial Mo sites initiated charge transfer, thus activating the basal plane. Consequently, the optimized Co-EG/SV-MoS2 electrode exhibited a substantially improved electrochemical performance. Flexible supercapacitors assembled with Co-EG/SV-MoS2 delivered a notable areal energy density of 0.51 mW h cm-2 at 0.84 mW cm-2 with good flexibility. Furthermore, supercapacitor devices were integrated with a strain sensor to create a self-powered system capable of real-time detection of human joint motion.

A novel method for repeated cerebrospinal fluid sampling and long-term monitoring of intracranial pressure in rats.

Cannulation implantation into the cisterna magna is an important procedure in cerebrospinal fluid (CSF) sampling and intracranial pressure (ICP) monitoring. The disadvantages of existing techniques include the risk of brain damage, compromised muscle mobility, and the complexity of the procedures. In the present study, the authors describe a modified, simple, and reliable procedure for long-term cannulation implantation into the cisterna magna in rats. The device consists of four parts: the puncture segment, the connection segment, the fixing segment, and the external segment. Intraoperative ICP monitoring and post-operative computed tomography (CT) scans were performed, which confirmed the accuracy and safety of this method. There were no limitations on the daily activities of the rats when long-term drainage was carried out for 1 week. This new technique offers an improved method of cannulation and will be a potentially useful method for CSF sampling and ICP monitoring in neuroscience research.

Fused-Deposition Modeling 3D Printing of Short-Cut Carbon-Fiber-Reinforced PA6 Composites for Strengthening, Toughening, and Light Weighting.

Additive manufacturing of carbon-fiber-reinforced polymer (CFRP) has been widely used in many fields. However, issues such as inconsistent fiber orientation distribution and void formation during the layer stacking process have hindered the further optimization of the composite material's performance. This study aimed to address these challenges by conducting a comprehensive investigation into the influence of carbon fiber content and printing parameters on the micro-morphology, thermal properties, and mechanical properties of PA6-CF composites. Additionally, a heat treatment process was proposed to enhance the interlayer bonding and tensile properties of the printed composites in the printing direction. The experimental results demonstrate that the PA6-CF25 composite achieved the highest tensile strength of 163 MPa under optimal heat treatment conditions: 120 °C for 7.5 h. This corresponds to a significant tensile strength enhancement of 406% compared to the unreinforced composites, which represents the highest reported improvement in the current field of CFRP-fused deposition 3D printing. Additionally, we have innovatively developed a single-layer monofilament CF-OD model to quantitatively analyze the influence of fiber orientation distribution on the properties of the composite material. Under specific heat treatment conditions, the sample exhibits an average orientation angle µ of 0.43 and an orientation angle variance of 8.02. The peak frequency of fiber orientation closely aligns with 0°, which corresponds to the printing direction. Finally, the study explored the lightweight applications of the composite material, showcasing the impressive specific energy absorption (SEA) value of 17,800 J/kg when implementing 3D-printed PA6-CF composites as fillers in automobile crash boxes.

In Situ Construction of the Fe-Cu Hydroxide Interlocking Structure with Solution-Derived Cu/Ag Current Collectors for Flexible Symmetric Supercapacitors.

The current collector serves as a crucial element in supercapacitors, acting as a medium between the electrode material and the substrate. Due to its excellent conductivity, a metal collector is typically favored. Enhancing the binding strength between the collector and the substrate as well as between the collector and the electrode material has emerged as a critical factor for enhancing the capacitance performance. In this study, a Ag film with a grass root-like structure was initially grown on a PI substrate through the surface modification and ion exchange (SMIE) process. This Ag interlocking structure contributes to strong binding between the PI substrate and Ag without compromising the mechanical properties of the Ag film. To further enhance the electrochemical properties at low scan rates, electroless-plated Cu was subsequently deposited on the Ag film to form the Cu/Ag current collector. Moreover, the Cu within the Cu/Ag current collector served as a precursor for the growth of FeOOH-Cu(OH)2 via a two-step in situ method. The resulting FeOOH-Cu(OH)2/Cu/Ag structure as a whole is binder-free. Supercapacitors employing symmetric FeOOH-Cu(OH)2/Cu/Ag structures were assembled, and their energy storage properties were investigated. The solution-based low-temperature process used in this study offers the potential for cost-effective and large-scale applications.

Bio-inspired interface engineering of Ag2O rooted on Au, Ni-modified filter paper for highly robust Zn-Ag2O batteries.

Flexible zinc-silver oxide (Zn-Ag2O) batteries have attracted extensive attention for comfortable wearable electronics owing to their stable output voltage, inherent safety, and environmental benignity. However, they suffer from inferior specific capacity and poor mechanical stability due to the low utilization of Ag2O cathodic material and weak interfacial adhesion of active material/substrate. Inspired by the nature of the tree root system, we develop an interface-engineered cathode, in which Ag2O nanoparticles are rooted on an Au, Ni co-modified filter paper substrate (CFP) through an electroless plating followed by an in situ electrochemical oxidation. The staggered-stacked Ag2O nanoparticles provide abundant electrochemically active sites and convenient ion diffusion paths, and the unique biological tree-root-like structure of the electrode material creates robust interlocking interfaces. A quasi-solid-state Zn-Ag2O battery assembled with a tree-root-like Ag2O/CFP cathode delivers a high areal specific capacity of 1.08 mAh cm-2 and long-term cycling durability with a capacity retention of 77.3% even after 100 cycles. Moreover, the device presents good mechanical stability under various flexural deformations, including bending, folding, and twisting, and exhibits minimal capacity changes after 1000 bending cycles. These findings suggest that the bio-inspired interface-engineered electrode structure is an efficient approach for developing flexible batteries with excellent electrochemical performance and mechanical properties.

SPIB acts as a tumor suppressor by activating the NFkB and JNK signaling pathways through MAP4K1 in colorectal cancer cells.

Spi-B transcription factor (SPIB) is a member of the E-twenty-six (ETS) transcription factor family. Previous studies have shown that the expression of SPIB is downregulated in human colorectal cancer tissues. The purpose of our study was to explore the biological function and related mechanism of SPIB in colorectal cancer cells. Our study found that SPIB could inhibit the proliferation, migration and invasion of CRC cells; inhibit angiogenesis; and induce CRC cells cycle arrest in G2/M phase and promote the apoptosis of CRC cells. We also found that compared with the control group, the 50% inhibitory concentration (IC50) values of oxaliplatin and 5-FU in the SPIB overexpression group were significantly reduced. Western blot results showed that the overexpression of SPIB upregulated cleaved-PARP(c-PARP), nuclear factor kB p65 (NFkB p65), phospho-NFkB p65 (p-NFkB P65), JNK1, and C-Jun protein expression levels compared with the control group. The silence of SPIB downregulated c-PARP, NFκB p65, p-NFκB p65, JNK1, and C-Jun protein expression levels. A dual-luciferase reporter assay showed that SPIB could activate the promoter of MAP4K1 and enhance the expression of MAP4K1. After silencing MAP4K1, the protein expression levels of c-PARP, NFkB P65, p-NFkB P65, JNK1, and C-Jun were downregulated. In summary, we found that SPIB is a tumor suppressor in colorectal cancer cells and that SPIB sensitizes colorectal cancer cells to oxaliplatin and 5-FU, SPIB exerts its anti-colorectal cancer effect by activating the NFkB and JNK signaling pathways through MAP4K1. The above findings may provide a reference for new molecular markers and therapeutic targets for CRC.

Case Report: Treatment of Anti-MDA5-Positive Amyopathic Dermatomyositis Accompanied by a Rapidly Progressive Interstitial Lung Diseases With Methylprednisolone Pulse Therapy Combined With Cyclosporine A and Hydroxychloroquine.

Introduction: Patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive amyopathic dermatomyositis (ADM) often develop rapidly progressive interstitial lung diseases (RP-ILD), with poor treatment success. Many studies have shown that this is the main cause of death in patients with anti-MDA5 antibody-positive ADM. Case Presentation: A 37-years-old woman developed a cough, shortness of breath, and a rash on both hands, which resembled Gottron's signs. Upon laboratory examination, the results were as follows: antinuclear antibody (ANA) positive; anti-Ro52 antibody positive; and anti-MDA5 antibody positive. Pulmonary high-resolution CT (HRCT) scan showed pulmonary interstitial inflammatory changes, and mediastinal and subcutaneous emphysema. She was finally diagnosed with anti-MDA5 antibody-positive ADM accompanied by RP-ILD. She was first given high-dose-steroid pulse therapy with methylprednisolone (500 mg per day for 3 days) followed by methylprednisolone (40 mg, daily), cyclosporine A (100 mg, twice per day), and hydroxychloroquine (200 mg, twice per day). Since her discharge from our hospital in March of 2018, she has maintained the methylprednisolone therapy (tapered to 10 mg daily), cyclosporine A (100 mg, twice per day), and hydroxychloroquine (200 mg, twice per day). Outcomes: Pulmonary HRCT scans taken on 4, 9, and 26 months after her discharge from our hospital showed that the interstitial pneumonitis had significantly improved and that mediastinal and subcutaneous emphysema had been gradually absorbed. The patient can now participate in regular work and activities of daily living. Conclusion: The treatment of methylprednisolone pulse therapy combined with cyclosporine A and hydroxychloroquine may be an option for the RP-ILD accompanied by anti-MDA-positive ADM. After the acute phase, this combination therapy strategy is helpful to the disease control of patients.

Matrix metalloproteinase-2 plays a critical role in overload induced skeletal muscle hypertrophy.

BACKGROUND: extracellular matrix (ECM) components are instrumental in maintaining homeostasis and muscle fiber functional integrity. Skeletal muscle hypertrophy is associated with ECM remodeling. Specifically, recent studies have reported the involvement of matrix metalloproteinases (MMPs) in muscle ECM remodeling. However, the functional role of MMPs in muscle hypertrophy remains largely unknown. METHODS: in this study, we examined the role of MMP-2 in skeletal muscle hypertrophy using a previously validated method where the plantaris muscle of mice were subjected to mechanical overload due to the surgical removal of synergist muscles (gastrocnemius and soleus). RESULTS: following two weeks of overload, we observed a significant increase in MMP-2 activity and up-regulation of ECM components and remodeling enzymes in the plantaris muscles of wild-type mice. However, MMP-2 knockout mice developed significantly less hypertrophy and ECM remodeling in response to overload compared to their wild-type littermates. Investigation of protein synthesis rate and Akt/mTOR signaling revealed no difference between wild-type and MMP-2 knockout mice, suggesting that a difference in hypertrophy was independent of protein synthesis. CONCLUSION: taken together, our results suggest that MMP-2 is a key mediator of ECM remodeling in the setting of skeletal muscle hypertrophy.

Matrix metalloproteinase-2 plays a critical role in overload induced skeletal muscle hypertrophy.

BACKGROUND: extracellular matrix (ECM) components are instrumental in maintaining homeostasis and muscle fiber functional integrity. Skeletal muscle hypertrophy is associated with ECM remodeling. Specifically, recent studies have reported the involvement of matrix metalloproteinases (MMPs) in muscle ECM remodeling. However, the functional role of MMPs in muscle hypertrophy remains largely unknown. METHODS: in this study, we examined the role of MMP-2 in skeletal muscle hypertrophy using a previously validated method where the plantaris muscle of mice were subjected to mechanical overload due to the surgical removal of synergist muscles (gastrocnemius and soleus). RESULTS: following two weeks of overload, we observed a significant increase in MMP-2 activity and up-regulation of ECM components and remodeling enzymes in the plantaris muscles of wild-type mice. However, MMP-2 knockout mice developed significantly less hypertrophy and ECM remodeling in response to overload compared to their wild-type littermates. Investigation of protein synthesis rate and Akt/mTOR signaling revealed no difference between wild-type and MMP-2 knockout mice, suggesting that a difference in hypertrophy was independent of protein synthesis. CONCLUSION: taken together, our results suggest that MMP-2 is a key mediator of ECM remodeling in the setting of skeletal muscle hypertrophy.

Original article Muscle extracellular matrix degradation and contractibility following tendon rupture and disuse.

Muscle extracellular matrix (ECM) plays an important role in maintaining muscular integrity and force transduction. However, the role of ECM in skeletal muscle atrophy remains unknown. In this study, we employed two clinically relevant mouse models of Achillotenotomy and hindlimb suspension to simulate Achilles tendon rupture and hindlimb disuse. The gastrocnemius was harvested following two weeks of treatment. We hypothesized that degradation of muscle ECM basement membrane lead to dysfunction of muscle contractility. Our results demonstrated a significant reduction of gastrocnemius single twitch force, isometric tetanic force, and contraction velocity following tendon rupture (p<0.001), but not disuse. Additionally, up-regulation of matrix metalloproteinase-2 (MMP-2) was observed only after tendon rupture (p=0.00234). These findings suggest that ECM remodeling and basement membrane degradation due to MMP-2 may be responsible for declined muscle contractibility. Inhibiting ECM degradation enzymes may be a potential treatment strategy for skeletal muscle atrophy after tendon rupture.

Peripheral nerve repair in rats using composite hydrogel-filled aligned nanofiber conduits with incorporated nerve growth factor.

Repair of peripheral nerve defects with current synthetic, tubular nerve conduits generally shows inferior recovery when compared with using nerve autografts, the current gold standard. We tested the ability of composite collagen and hyaluronan hydrogels, with and without the nerve growth factor (NGF), to stimulate neurite extension on a promising aligned, nanofiber poly-L-lactide-co-caprolactone (PLCL) scaffold. In vitro, the hydrogels significantly increased neurite extension from dorsal root ganglia explants. Consistent with these results, the addition of hydrogels as luminal fillers within aligned, nanofiber tubular PLCL conduits led to improved sensory function compared to autograft repair in a critical-size defect in the sciatic nerve in a rat model. Sensory recovery was assessed 3 and 12 weeks after repair using a withdrawal assay from thermal stimulation. The addition of hydrogel did not enhance recovery of motor function in the rat model. The NGF led to dose-dependent improvements in neurite out-growth in vitro, but did not have a significant effect in vivo. In summary, composite collagen/hyaluronan hydrogels enhanced sensory neurite outgrowth in vitro and sensory recovery in vivo. The use of such hydrogels as luminal fillers for tubular nerve conduits may therefore be useful in assisting restoration of protective sensation following peripheral nerve injury.

Functional motor recovery after peripheral nerve repair with an aligned nanofiber tubular conduit in a rat model.

AIM: Current synthetic tubular conduits are inferior to nerve autograft for the repair of segmental peripheral nerve injuries. We examined motor outcomes with the use of longitudinally aligned poly (L-lactide-co-caprolactone) nanofiber conduits for repair of nerve gap injury in a rat model. METHODS: Ten-millimeter segments of sciatic nerve were resected in 44 Lewis rats. The gaps were either left unrepaired (n = 6), repaired with nerve autograft (n = 19), or repaired with conduit (n = 19). After 12 weeks, nerve conduction latency, compound muscle action potential amplitude, muscle force and muscle mass were measured. The numbers of axons and axon diameters both within the grafts and distally were determined. RESULTS: After 12 weeks, gastrocnemius isometric tetanic force and muscle mass for the conduit group reached 85 and 82% of autograft values, respectively. Nerve conduction and compound muscle action potential were not significantly different between these two groups, although the latter approached significance. There was no recovery in the unrepaired group. CONCLUSION: Muscle recovery for the animals treated with this aligned nanofiber conduit approached that of autograft, suggesting the importance of internal conduit structure for nerve repair.

[Clinical research of patients with congenital anosmia].

OBJECTIVE: To report on a series of patients with congenital anosmia, and to discuss its classification and clinical characteristics. METHODS: Eight patients with congenital anosmia were reviewed retrospectively. Four of eight cases were congenital anosmia with other abnormalities, including three cases with Kallmann's syndrome, one with hypoplasia of nasal cavity and nasal sinus. Four cases were isolated congenital anosmia. A thorough medical and chemosensory history, physical examination, nasal endoscopy, T&T olfactory testing, olfactory event-related potentials and sinonasal computed tomography scan were performed in all patients. Magnetic resonance image of olfactory pathway was available in seven cases, and olfactory biopsies were done in two cases. RESULTS: All patients reported had never been able to smell anything. ENT physical examination and nasal endoscopy were normal, except one case with hypoplasia of nasal cavity. Subjective olfactory test indicated all of them were anosmia. No olfactory event-related potentials to maximum stimulus were obtained. Magnetic resonance imaging revealed the absence of olfactory bulbs and tracts in six cases, hypoplasia of bilateral olfactory bulbs and tracts in one case. Computed tomography scan indicated normal except hypoplasia of nasal cavity and sinus in one case. Three cases with Kallmann syndrome showed poor development of both primary and secondary sexual characteristics and had decreased serum luteinizing hormone, follicle-stimulating hormone, testosterone and estradiol. CONCLUSIONS: Diagnosis of congenital anosmia is established on chief complain, physical examination, nasal endoscopy, olfactory testing and olfactory imaging. Magnetic resonance imaging of olfactory pathway is indispensable.