Positive Fibers Research Articles

Validation of Peripheral Neuromodulation Mechanisms of Icariin in Knee Osteoarthritis–Related Chronic Pain

ABSTRACTKnee osteoarthritis (KOA) is a chronic degenerative joint disease‐causing chronic pain and disability. Neuromodulation of subchondral bone affects KOA‐related pain and involves dorsal root ganglion (DRG). Our previous studies have demonstrated efficacy of icariin (ICA) in treating KOA, but neuromodulation mechanisms in peripheral nerves associated with the treatment of chronic pain in KOA remain unclear. This study aimed to investigate peripheral neuromodulation mechanisms of ICA in KOA‐related chronic pain: (1) assessing therapeutic effect of ICA in a rat model of KOA‐induced chronic pain; (2) investigating changes in pain‐related nerve fibres and transient receptor potential vanilloid Subfamily 1 (TRPV1) pathway in subchondral bone following ICA treatment; and (3) exploring expression of pain‐related Nogo‐A/TRPV1 pathway in DRG, thereby elucidating neurotransmission of pain. Experimental results confirmed the curative effect of ICA on KOA by relieving chronic pain and pathological changes. ICA also effectively reduced bone remodelling, the area of pain‐related positive nerve fibres and expression of TRPV1 in subchondral bone. Furthermore, ICA downregulated pain‐related Nogo‐A/TRPV1 pathway in the DRG. These findings provide new mechanistic insights into the therapeutic potential of ICA in relieving peripheral nervous system‐related chronic pain in KOA.

A spinal neural circuit for electroacupuncture that regulates gastric functional disorders

ObjectiveAcupuncture therapies are known for their effectiveness in treating a variety of gastric diseases, although the mechanisms underlying these effects are not fully understood. This study tested the effectiveness of electroacupuncture (EA) at acupoints Zhongwan (RN12) and Weishu (BL21) for managing gastric motility disorder (GMD) and investigated the underlying mechanisms involved. MethodsA GMD model was used to evaluate the impact of EA on various aspects of gastric function including the amplitude of gastric motility, electrogastrogram, food intake, and the rate of gastric emptying. Immunofluorescence techniques were used to explore the activation of spinal neurons by EA, specifically examining the presence of cholera toxin B subunit (CTB)-positive neurons and fibers emanating from acupoints RN12 and BL21. The stimulation of γ-aminobutyric acid (GABA)-ergic neurons in the spinal dorsal horn, the inhibition of sympathetic preganglionic neurons in the spinal lateral horn, and their collective effects on the activity of sympathetic nerves were examined. ResultsEA at RN12 and BL21 significantly improved gastric motility compromised by GMD. Notably, EA activated spinal neurons, with CTB-positive neurons and fibers from RN12 and BL21 being detectable in both the dorsal root ganglia and the spinal dorsal horn. Further analysis revealed that EA at these acupoints not only stimulated GABAergic neurons in the spinal dorsal horn but also suppressed sympathetic preganglionic neurons in the spinal lateral horn, effectively reducing excessive activity of sympathetic nerves triggered by GMD. ConclusionEA treatment at RN12 and BL21 effectively enhances gastric motility in a GMD model. The therapeutic efficacy of this approach is attributed to the activation of spinal neurons and the modulation of the spinal GABAergic-sympathetic pathway, providing a neurobiological foundation for the role of acupuncture in treating gastric disorders.

Overexpression of CGRP receptor attenuates tendon graft degeneration in anterior cruciate ligament reconstruction.

Cell apoptosis or necrosis, extracellular matrix loss, and excessive inflammation may induce tendon graft degeneration. The impairment in the regeneration capability of nerve fibers and blood vessels may be the critical cause. Calcitonin gene-related peptide (CGRP), exhibiting a short half-life, favors cell proliferation, nerve fiber regeneration and angiogenesis. We aimed to investigate the effects of CGRP receptor-mediated signaling on tendon graft integrity and study if the modulation pathways are ascribed to cell proliferation, nerve fiber and blood vessel regeneration. A total of three groups in mice with ACL reconstruction were established: the control group (PBS treatment), the adenovirus vectors expressing CGRP receptor (CALCRL) treated group (Adv-Calcrl treatment), and the adenovirus vectors carrying shRNA targeting Calcrl treated group (Adv-shCalcrl treatment). The histological assessment indicated the Adv-Calcrl treatment was favored while the Adv-shCalcrl significantly impaired tendon graft integrity. TUNEL staining revealed a significant decreased number of apoptotic cells in the Adv-Calcrl group relative to the control group and the adv-shCalcrl group. Compared to the control group and the Adv-shCalcrl group, the Adv-Calcrl group showed significantly enhanced proliferation of nestin positive cells. Of note, the Adv-Calcrl treatment significantly increased EMCN expression at the tendon graft relative to the control and the Adv-shCalcrl groups, which may be ascribed to attenuation of the Hippo signaling pathway. Importantly, the Adv-Calcrl treatment significantly increased sensory nerve fibers and also PIEZO2 levels. Our results demonstrate the activation of CGRP receptor-mediated signaling attenuated tendon graft degeneration, which was ascribed to enhanced proliferation of Nestin positive cells, angiogenesis, and nerve fiber outgrowth.

Automated immunohistochemistry of intra-epidermal nerve fibres in skin biopsies: A proof-of-concept study.

To develop a standardised, automated protocol for detecting protein gene product 9.5 (PGP9.5) positive intra-epidermal nerve fibres (IENFs) in skin biopsies, transitioning from the established manual technique to an automated platform. This automated method, although currently intended for research applications, may improve the accessibility of this diagnostic test for small fibre neuropathy in clinical settings. Skin biopsies (n = 274) from 100 participants (fibromyalgia syndrome n = 62; idiopathic small fibre neuropathy: n = 16; healthy volunteers: n = 22) were processed using an automated immunohistochemistry platform. IENF quantification was performed by blinded examiners, with reliability assessed via a two-way mixed-effects model to evaluate inter- and intra-observer variability. The automated staining system reproduced intra-epidermal nerve fibre density (IENFD) counts consistent with free-floating sections (mean ± standard deviation: free-floating: 5.6 ± 3.4 fibres/mm; automated: 5.9 ± 3.2 fibres/mm). A median difference of 0.3 with a lower bound 95% Confidence Interval (CI) at -0.00005 established non-inferiority against a margin of -0.4 (p = .08). Specifically, the inter-class correlation coefficient (class denotes consistency in measured observations) was 99% (95% CI: 0.9-1), indicating excellent agreement between free-floating and automated methods. The inter- and intra-class coefficient between examiners were both 99% (95% CI: 0.9-0.1) for IENFD, demonstrating high reliability using sections stained using the automated method. Automated immunohistochemistry provides high-throughput reliable and reproducible intra-epidermal nerve fibre quantification. This method, although currently proof-of-concept, for research use only, may be more widely deployed in histopathology laboratories to increase the adoption of IENFD assessment for the diagnosis of peripheral neuropathies.

STUDYING DROUGHT RESISTANCE AND SOME TECHNOLOGICAL INDICATORS OF FIBER OF COLLECTION VARIETIES COTTON

The purpose of the study was to study the adaptive ability to drought of collection varieties of cotton of the species G.hirsutum L. and G.barbadense L. with subsequent assessment of the technological properties of the fiber. An analysis of stress-depression of seed germination in a sucrose solution was used as an indicator of plant resistance to drought. The technological properties of the fiber were analyzed using the HVI (High Volume Instrument) electronic system in accordance with the unified international classification. It was established that, with the same intensity of the extreme factor, varieties of the same type of cotton differed significantly in the amplitude of changes in the physiological indicator, which made it possible to identify drought-resistant samples. Varieties Agdash-3, Ganja-2, AF-16, Karabakh-11, Zafar, Akala 1517 of the species G.hirsutum L. and varieties S-6002, 5230-V, Aspero, S-6022, AP-154, Agdash-21, Termez-74 of the species G. barbadense L. were characterized by drought resistance. All drought-resistant varieties of the species G. barbadense L. are characterized by a complex of positive fiber quality indicators. The variety Zafar within the species G.hirsutum L. was superior to other genotypes in this indicator. These cotton varieties are recommended to breeders for use in various breeding programs.

Decreased skeletal muscle intramyocellular lipid droplet-mitochondrial contact contributes to myosteatosis in cancer cachexia.

Cancer cachexia, the unintentional loss of lean mass, contributes to functional dependency, poor treatment outcomes, and decreased survival. Although its pathogenicity is multifactorial, metabolic dysfunction remains a hallmark of cachexia. However, significant knowledge gaps exist in understanding the role of skeletal muscle lipid metabolism and dynamics in this condition. We examined skeletal muscle metabolic dysfunction, intramyocellular lipid droplet (LD) content, LD morphology and subcellular distribution, and LD-mitochondrial interactions using the Lewis lung carcinoma (LLC) murine model of cachexia. C57/BL6 male mice (n = 20) were implanted with LLC cells (106) in the right flank or underwent PBS sham injections. Skeletal muscle was excised for transmission electron microscopy (TEM; soleus), oil red O/lipid staining [tibialis anterior (TA)], and protein (gastrocnemius). LLC mice had a greater number (232%; P = 0.006) and size (130%; P = 0.023) of intramyocellular LDs further supported by increased oil-red O positive (87%; P = 0.0109) and "very high" oil-red O positive (178%; P = 0.0002) fibers compared with controls and this was inversely correlated with fiber size (R2 = 0.5294; P < 0.0001). Morphological analyses of LDs show increased elongation and complexity [aspect ratio: intermyofibrillar (IMF) = 9%, P = 0.046) with decreases in circularity [circularity: subsarcolemmal (SS) = 6%, P = 0.042] or roundness (roundness: whole = 10%, P = 0.033; IMF = 8%, P = 0.038) as well as decreased LD-mitochondria touch (-15%; P = 0.006), contact length (-38%; P = 0.036), and relative contact (86%; P = 0.004). Furthermore, dysregulation in lipid metabolism (adiponectin, CPT1b) and LD-associated proteins, perilipin-2 and perilipin-5, in cachectic muscle (P < 0.05) were observed. Collectively, we provide evidence that skeletal muscle myosteatosis, altered LD morphology, and decreased LD-mitochondrial interactions occur in a preclinical model of cancer cachexia.NEW & NOTEWORTHY We sought to advance our understanding of skeletal muscle lipid metabolism and dynamics in cancer cachexia. Cachexia increased the number and size of intramyocellular lipid droplets (LDs). Furthermore, decreases in LD-mitochondrial touch, contact length, and relative contact along with increased LD shape complexity with decreases in circularity and roundness. Dysregulation in lipid metabolism and LD-associated proteins was also documented. Collectively, we show that myosteatosis, altered LD morphology, and decreased LD-mitochondrial interactions occur in cancer cachexia.

Protective effect of equol intake on bladder dysfunction in a rat model of bladder outlet obstruction.

This study evaluates the impact of equol, a metabolite of soy isoflavone, on bladder dysfunction in rats with bladder outlet obstruction (BOO). In addition, we investigate its potential as a neuroprotective agent for the obstructed bladder and discuss its applicability in managing overactive bladder (OAB). Eighteen male Sprague-Dawley rats were divided into three groups (six rats per group) during the rearing period. The Sham and C-BOO groups received an equol-free diet, while the E-BOO group received equol supplementation (0.25 g/kg). At 8 weeks old, rats underwent BOO surgery, followed by continuous cystometry after 4 weeks of rearing. The urinary oxidative stress markers (8-hydroxy-2'-deoxyguanosine and malondialdehyde) were measured, and the bladder histology was analyzed using hematoxylin-eosin, Masson's trichrome, and immunohistochemical staining (neurofilament heavy chain for myelinated nerves, peripherin for unmyelinated nerves, and malondialdehyde). Equol reduced BOO-induced smooth muscle layer fibrosis, significantly prolonged the micturition interval (C-BOO: 193 s, E-BOO: 438 s) and increased the micturition volume (C-BOO: 0.54 mL, E-BOO: 1.02 mL) compared to the C-BOO group. Equol inhibited the increase in urinary and bladder tissue malondialdehyde levels. While the C-BOO group exhibited reduced peripherin alone positive nerve fibers within the smooth muscle layer, equol effectively attenuated this decline. Equol reduces lipid peroxidation and smooth muscle layer fibrosis in the bladder and exhibited neuroprotective effects on bladder nerves (peripheral nerves) and prevented the development of bladder dysfunction associated with BOO in rats. Consumption of equol is promising for the prevention of OAB associated with BOO.

Auricular acupuncture plays a neuroprotective role in 6-hydroxydopamine-induced Parkinson's disease in rats

BackgroundParkinson's disease (PD) is the second-most common neurodegenerative disease. Currently, PD treatment is symptomatic and involves the use of dopamine-based therapies. This study investigated auricular acupuncture on motor and cognitive abilities in rats with 6-OHDA-induced PD. MethodsA PD rat model was established by bilaterally injecting 6-OHDA into the lateral dorsal striatum. Then, 2- or 15-Hz auricular electroacupuncture (EA) was applied to the auricular CO15 and CO12 points bilaterally for 20 min three times a week for four consecutive weeks. ResultsBoth the latency to fall and rest time of the open field test in the EA15 group were greater than in the 6-OHDA group (p < 0.001 and p < 0.05). The time spent on the two-object recognition task was greater in the EA15 group and EA2 group than in the 6-OHDA group (p < 0.01 and p < 0.05). More tyrosine hydroxylase (TH)-positive neurons and fibers were noted in the dorsolateral striatum and substantia nigra (SN) (all p < 0.05). TH expression in the SN was greater in the EA15 group than that in the 6-OHDA group (p < 0.05), while α-synuclein expression in the SN was stronger in the 6-OHDA group than in the EA15 group (p < 0.05). The l-DOPA level in the striatum was higher in the EA15 group than in the 6-OHDA group (p < 0.05). ConclusionAccording to the results, rats with 6-OHDA-induced PD may benefit from auricular EA in terms of motor and cognitive behavior as well as neuroprotection.

Atorvastatin, etanercept and the nephrogenic cardiac sympathetic remodeling in chronic renal failure rats.

Chronic renal failure (CRF) patients are predisposed to arrhythmias, while the detailed mechanisms are unclear. We hypothesized the chronic inflammatory state of CRF patients may lead to cardiac sympathetic remodeling, increasing the incidence of ventricular arrhythmia (VA) and sudden cardiac death. And explored the role of atorvastatin and etanercept in this process. A total of 48 rats were randomly divided into sham operation group (Sham group), CRF group, CRF + atorvastatin group (CRF + statin group), and CRF + etanercept group (CRF + rhTNFR-Fc group). Sympathetic nerve remodeling was assessed by immunofluorescence of growth-associated protein 43 (GAP-43) and tyrosine hydroxylase positive area fraction. Electrophysiological testing was performed to assess the incidence of VA by assessing the ventricular effective refractory period and ventricular fibrillation threshold. The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta were determined by Western blotting and enzyme-linked immunosorbent assay. Echocardiogram showed that compared with the Sham group, left ventricular end-systolic diameter and ventricular weight/body weight ratio were significantly higher in the CRF group. Hematoxylin-eosin and Masson staining indicated that myocardial fibers were broken, disordered, and fibrotic in the CRF group. Western blotting, enzyme-linked immunosorbent assay, immunofluorescence and electrophysiological examination suggested that compared with the Sham group, GAP-43 and TNF-α proteins were significantly upregulated, GAP-43 and tyrosine hydroxylase positive nerve fiber area was increased, and ventricular fibrillation threshold was significantly decreased in the CRF group. The above effects were inhibited in the CRF + statin group and the CRF + rhTNFR-Fc group. In CRF rats, TNF-α was upregulated, cardiac sympathetic remodeling was more severe, and the nephrogenic cardiac sympathetic remodeling existed. Atorvastatin and etanercept could downregulate the expression of TNF-α or inhibit its activity, thus inhibited the above effects, and reduced the occurrence of VA and sudden cardiac death.

Pure-quartic soliton in a birefringence-managed fiber laser

Pure-quartic soliton (PQS) fiber lasers with a great variety of operating regimes have aroused considerable interest in high-energy ultrashort pulses and novel soliton patterns. Here, we numerically investigate the generation and dynamic properties of birefringence-managed pure-quartic soliton (BMPQS) in a positive fourth-order dispersion (FOD) fiber laser consisting of single-mode fibers and a section of polarization-maintaining fiber. The formation mechanism of the chirp-free BMPQS is dominated by the phase-matching effect, which arises from the co-actions of the birefringence, positive FOD, and nonlinear effects. It is observed that a higher FOD coefficient leads to energy transfer between the spectral sidebands inside the BMPQS. Moreover, the evolution of the BMPQS with the increase of the pump power confirms the phase-matching theory. Finally, the BMPQS molecule can be obtained with further increasing the pump power. This work offers a new avenue to create chirp-free pulses in positive FOD fiber lasers and enriches the sub-families of PQSs.

Histological changes in the olfactory bulb and rostral migratory stream due to interruption of olfactory input

ObjectivePeriglomerular and granule cells in the adult mammalian olfactory bulb modulate olfactory signal transmission. These cells originate from the subventricular zone, migrate to the olfactory bulb via the Rostral Migratory Stream (RMS), and differentiate into mature cells within the olfactory bulb throughout postnatal life. While the regulation of neuroblast development is known to be affected by external stimuli, there is a lack of information concerning changes that occur during the recovery process after injury caused by external stimuli. To address this gap in research, the present study conducted histological observations to investigate changes in the olfactory bulb and RMS occurring after the degeneration and regeneration of olfactory neurons. MethodsTo create a model of olfactory neurodegeneration, adult mice were administered methimazole intraperitoneally. Nasal tissue and whole brains were removed 3, 7, 14 and 28 days after methimazole administration, and EdU was administered 2 and 4 h before removal of these tissues to monitor dividing cells in the RMS. Methimazole-untreated mice were used as controls. Olfactory nerve fibers entering the olfactory glomerulus were observed immunohistochemically using anti-olfactory marker protein. In the brain tissue, the entire RMS was observed and the volume and total number of cells in the RMS were measured. In addition, the number of neuroblasts and dividing neuroblasts passing through the RMS were measured using anti-doublecortin and anti-EdU antibodies, respectively. Statistical analysis was performed using the Tukey test. ResultsOlfactory epithelium degenerated was observed after methimazole administration, and recovered after 28 days. In the olfactory glomeruli, degeneration of OMP fibers began after methimazole administration, and after day 14, OMP fibers were reduced or absent by day 28, and overall OMP positive fibers were less than 20%. Glomerular volume tended to decrease after methimazole administration and did not appear to recover, even 28 days after recovery of the olfactory epithelium. In the RMS, EdU-positive cells decreased on day 3 and began to increase on day 7. However, they did not recover to the same levels as the control methimazole-untreated mice even after 28 days. ConclusionThese results suggest that the division and maturation of neuroblasts migrating from the RMS was suppressed by olfactory nerve degeneration or the disruption of olfactory input.

Cortico-cortical evoked potentials of language tracts in minimally invasive glioma surgery guided by Penfield stimulation

ObjectiveWe investigated the feasibility of recording cortico-cortical evoked potentials (CCEPs) in patients with low- and high-grade glioma. We compared CCEPs during awake and asleep surgery, as well as those stimulated from the functional Broca area and recorded from the functional Wernicke area (BtW), and vice versa (WtB). We also analyzed CCEP properties according to tumor location, histopathology, and aphasia. MethodsWe included 20 patients who underwent minimally invasive surgery in an asleep-awake-asleep setting. Strip electrode placement was guided by classical Penfield stimulation of positive language sites and fiber tracking of the arcuate fascicle. CCEPs were elicited with alternating monophasic single pulses of 1.1 Hz frequency and recorded as averaged signals. Intraoperatively, there was no post-processing of the signal. ResultsNinety-seven CCEPs from 19 patients were analyzed. There was no significant difference in CCEP properties when comparing awake versus asleep, nor BtW versus WtB. CCEP amplitude and latency were affected by tumor location and histopathology. CCEP features after tumor resection correlated with short- and long-term postoperative aphasia. ConclusionCCEP recordings are feasible during minimally invasive surgery. CCEPs might be surrogate markers for altered connectivity of the language tracts. SignificanceThis study may guide the incorporation of CCEPs into intraoperative neurophysiological monitoring.

Predictive models for mechanical properties of hybrid fibres reinforced concrete containing bamboo and basalt fibres

The aim of this study was to investigate hybrid fibre reinforced concrete containing natural Bamboo and basalt fibres and forecasting the effect of these fibres on Mechanical properties. The contents of Basalt fibres were (0%, 0.25%, 0.50%, 0.75% and 1.00%). The mechanical performance of the hybrid fibre-reinforced concrete was studied in terms of compressive, splitting tensile and flexural strengths. All the samples were tested at the ages of 7, 14, and 28 days. The results showed that an increase in fibre percentages led to a reduction in the concrete slump. It was also found that 0.75% Basalt fibres with 1% bamboo fibres resulted in the optimum performance of the mechanical properties of the concrete. Based on regression models, it was found that bamboo fibres have negative impact on the compressive and splitting tensile strength while basalt fibres enhanced this strength, however, the negative effect of bamboo fibres reduces with the age of concrete. While the effect of bamboo fibres on flexural strength was positive and basalt fibres have negative impact on it. It was concluded that the bamboo and basalt fibre have good relation in overall improving the mechanical properties of hybrid fibre reinforced concrete.

Netrin-1 Role in Nociceptive Neuron Sprouting through Activation of DCC Signaling in a Rat Model of Bone Cancer Pain.

Bone cancer pain (BCP) is a common primary or metastatic bone cancer complication. Netrin-1 plays an essential role in neurite elongation and pain sensitization. This study aimed to determine the role of netrin-1 from the metastatic bone microenvironment in BCP development and identify the associated signaling pathway for the strategy of BCP management. The rat BCP model was established by intratibial implantation of Walker 256 cells. Von Frey filaments measured the mechanical pain threshold. Movement-induced pain was assessed using limb use scores. Expressions of associated molecules in the affected tibias or dorsal root ganglia (DRG) were measured by immunofluorescence, immunohistochemistry, real-time quantitative polymerase chain reaction, or western blotting. Transduction of deleted in colorectal cancer (DCC) signaling was inhibited by intrathecal injection of DCC-siRNA. In BCP rats, the presence of calcitonin gene-related peptide (CGRP)-positive nerve fibers increased in the metastatic bone lesions. The metastatic site showed enrichment of well-differentiated osteoclasts and expressions of netrin-1 and its attractive receptor DCC. Upregulation of DCC and increased phosphorylation levels of focal adhesion kinase (FAK) and Rac family small GTPase 1/Cell division cycle 42 (Rac1/Cdc42) were found in the DRG. Intrathecal administration of DCC-siRNA led to a significant reduction in FAK and Rac1/Cdc42 phosphorylation levels in the DRG, decreased nociceptive nerve innervation, and improved pain behaviors. Netrin-1 may contribute to the activation of the BCP by inducing nociceptive nerve innervation and improving pain behaviors.

NGF Signaling Exacerbates KOA Peripheral Hyperalgesia via the Increased TRPV1-Labeled Synovial Sensory Innervation in KOA Rats.

Knee osteoarthritis (KOA) pain is caused by nociceptors, which are actually sensory nerve fiber endings that can detect stimuli to produce and transmit pain signals, and high levels of NGF in synovial tissue led to peripheral hyperalgesia in KOA. The purpose of this study is to investigate how sensory nerve fibers respond to the NGF/TrKA signal pathway and mediate the peripheral hyperalgesia in KOA rats. Forty SD male rats were randomly divided into 4 groups: normal, KOA, KOA + NGF, and KOA + siRNA TrKA. KOA model rats were induced by anterior cruciate ligament transection (ACLT). Mechanical and cold withdrawal thresholds (MWT and CWT) were measured 4 times in each group. The synovial tissues were harvested on day 28, and the expressions of NGF, TrKA, TRPV1, IL-1β, and PGP9.5 were determined using western blot, qPCR, and immunofluorescence staining. The primary rat fibroblast-like synoviocytes (FLSs) and DRG cells were divided into 4 groups as in vivo. The expressions of NGF, TrKA, TRPV1, and CGRP in vitro were determined using western blot and qPCR. KOA and intra-articular injection with NGF protein increased both mRNA and protein levels, not only TRPV1, PGP 9.5, and IL-1β in the synovial tissue, but also TRPV1, PGP 9.5, and S100 in the DRG tissue, while above changes were partly reversed after siRNA TrKA intervention. Besides, siRNA TrKA could improve peripheral hyperalgesia and decreased the TRPV1 positive nerve fiber innervation in synovial tissue. The results in vitro were consistent with those in vivo. This study showed the activation of the NGF/TrKA signaling pathway in KOA promoted the release of pain mediators, increased the innervation of sensory nerve fibers in the synovium, and worsened peripheral hyperalgesia. It also showed increased TRPV1 positive sensory innervation in KOA was mediated by NGF/TrKA signaling and exacerbated peripheral hyperalgesia.

High-Performance All-Textile Triboelectric Nanogenerator toward Intelligent Sports Sensing and Biomechanical Energy Harvesting.

Merging textiles with advanced energy harvesting technology via triboelectric effects brings novel insights into self-powered wearable textile electronics. However, fabrication of a comfortable textile-based triboelectric nanogenerator (TENG) with high outputs remains challenging. Herein, we propose a highly flexible, tailorable, single-electrode all-textile TENG (t-TENG) with both wear comfort and high outputs. A dielectric modulated porous composite coating containing poly(vinylidene fluoride)-hexafluoropropylene copolymer and barium titanate nanoparticles is constructed on conductive fabric to counterpart with highly positive glass fiber fabric through knotted yarn bonding, maintaining the superiority of textiles and strong triboelectricity. Through the synergistic optimization of charge storage via dielectric modulation and charge dissipation offset by electrical poling, remarkable outputs (261 V, 1.5 μA, and 12.7 nC) are obtained from a miniaturized, lightweight t-TENG (2 × 2 cm2, 130 mg) with an instantaneous power density of 654.48 mW·m-2, as well as excellent electrical robustness and device durability over 20,000 cycles. The t-TENG also exhibits a high sensitivity of 3.438 V·kPa-1 in the force region (1-10 N), demonstrating great potential in TENG-based intelligent sports sensing applications for monitoring and correcting the basketball shooting hand and foot arch posture. Furthermore, over 110 light-emitting diode arrays can be lightened up by gently tapping this miniaturized t-TENG. It also offers a wearable power source scheme through integrating the single-electrode device into clothing and utilizing the skin as the grounded electrode, revealing its ease of integration and biomechanical energy harvesting capability. This work provides an attractive paradigm for next-generation textile electronics with well-balanced device performance and wear comfort.

A case of chronic pruritus developing at a noninjured nerve area in a patient with spinal cord injury: Role of protein gene product 9.5

AbstractA patient in her 60s with spinal cord injury developed pruriginous lesion only in a nerve‐noninjured area, although erythema resulting from scratching was also prominent in a nerve‐injured lesion. The area of protein gene product 9.5 (PGP9.5)‐positive nerve fibres within the nerve‐injured lesion was significantly reduced compared with the nerve‐noninjured area. This case suggests an essential role for PGP 9.5‐positive nerve fibres in the development of chronic pruritus.

Mrgprb2-dependent Mast Cell Activation Plays a Crucial Role in Acute Colitis

Background & AimsMast cells (MCs) are typically found at mucosal surfaces, where their IgE-dependent activation plays a central role in allergic diseases. Over the past years, signaling through Mas-related G protein-coupled receptor b2 (Mrgprb2) in mice and MRGPRX2 in humans has gained a lot of interest as an alternative MC activation pathway with high therapeutic potential. The aim of this study was to explore the relevance of such IgE-independent, Mrgprb2-mediated signaling in colonic MCs in the healthy and acutely inflamed mouse colon. MethodsMrgprb2 expression and functionality was studied using a genetic labeling strategy combined with advanced microscopic imaging. Furthermore, Mrgprb2 knockout (Mrgprb2-/-) mice were used to determine the role of this pathway in a preclinical dextran sodium sulphate (DSS) colitis model. ResultsWe found that Mrgprb2 acts as a novel MC degranulation pathway in a large subset of connective tissue MCs (CTMCs) in the mouse distal colon. Acute DSS colitis induced a pronounced increase of Mrgprb2-expressing MCs, which were found in close association with Substance P (SP)-positive nerve fibers. Loss of Mrgprb2-mediated signaling impaired DSS-induced neutrophil influx and significantly impacted on acute colitis progression. ConclusionsOur findings uncover a novel, IgE-independent MC degranulation pathway in the mouse colon that plays a central role in acute colitis pathophysiology, mainly by safeguarding acute colitis progression and severity in mice. This pseudo allergic, Mrgprb2-induced signaling is part of a hitherto unconsidered colonic neuro-immune pathway and might have significant potential for the further development of effective therapeutic treatment strategies for gastrointestinal disorders, such as ulcerative colitis.

De novo aging-related NADPH diaphorase positive megaloneurites in the sacral spinal cord of aged dogs

We investigated aging-related changes in nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) in the spinal cord of aged dogs. At all levels of the spinal cord examined, NADPH-d activities were observed in neurons and fibers in the superficial dorsal horn (DH), dorsal gray commissure (DGC) and around the central canal (CC). A significant number of NADPH-d positive macro-diameter fibers, termed megaloneurites, were discovered in the sacral spinal cord (S1–S3) segments of aged dogs. The distribution of megaloneurites was characterized from the dorsal root entry zone (DREZ) into the superficial dorsal horn, along the lateral collateral pathway (LCP) to the region of sacral parasympathetic nucleus (SPN), DGC and around the CC, but not in the cervical, thoracic and lumbar segments. Double staining of NADPH-d histochemistry and immunofluorescence showed that NADPH-d positive megaloneurites co-localized with vasoactive intestinal peptide (VIP) immunoreactivity. We believed that megaloneurites may in part represent visceral afferent projections to the SPN and/or DGC. The NADPH-d megaloneurites in the aged sacral spinal cord indicated some anomalous changes in the neurites, which might account for a disturbance in the aging pathway of the autonomic and sensory nerve in the pelvic visceral organs.

Efficacy of rituximab on anti-TS-HDS and anti-FGFR3 positive small fiber neuropathy

Efficacy of rituximab on anti-TS-HDS and anti-FGFR3 positive small fiber neuropathy