Single Tail Research Articles

Online Hydraulic Stiffness Modulation of a Soft Robotic Fish tail for Improved Thrust and Efficiency.

This paper explores online stiffness modulation within a single tail stroke for swimming soft robots. Despite advances in stiffening mechanisms, little attention has been given to dynamically adjusting stiffness in real-time, presenting a challenge in developing mechanisms with the requisite bandwidth to match tail actuation. Achieving an optimal balance between thrust and efficiency in swimming soft robots remains elusive, and the paper addresses this challenge by proposing a novel mechanism for independent stiffness control, leveraging fluid-driven stiffening within a patterned pouch. Inspired by fluidic-driven actuation, this approach exhibits high bandwidth and facilitates significant stiffness changes. We perform experiments to demonstrate how this mechanism enhances both thrust and swimming efficiency. The tail actuation and fluid-driven stiffening can be optimized for a specific combination of thrust and efficiency, tailored to the desired maneuver type. The paper further explores the complex interaction between the soft body and surrounding fluid and provides fluid dynamics insights gained from the vortices created during actuation. Through frequency modulation and online stiffening, the study extends the Pareto front of achievable thrust generation and swimming efficiency.

Directional Adaptive Triboelectric Nanogenerator with Wind-Wave Synergy.

To enhance the adaptability and synergy of the triboelectric nanogenerator (TENG) in a wave environment, this paper introduces a directional adaptive triboelectric nanogenerator (DA-TENG) with wind-water synergistic action for wave energy collection. An innovative design combining a wind vane on the top and fan-shaped blade electrodes internally allows the DA-TENG to adjust its swinging direction adaptively to align with the direction of wave motion. The internal multiple power generation units work in coordination, effectively addressing the issues of low efficiency associated with spherical TENGs in capturing multidirectional wave energy. The DA-TENG demonstrates superior performance under various wind speed conditions, showcasing its practical application potential. Experimental results show that the DA-TENG, equipped with a single tail wind vane and a 700 g mass block, can achieve an output voltage, current, and charge of 374.97 V, 84.77 μA, and 622.69 nC under a mild wind environment. Its peak power density reaches 7.51 W m-3, enabling successful data transmission for a wireless temperature and humidity sensor and powering 248 light-emitting diodes (LEDs). This research expands the possibilities of omnidirectional wave energy collection and the collaborative operation of multiple power generation units, offering an effective method for powering low-power maritime devices.

Ultrasensitive Dual ELONA/SERS-RPA Multiplex Diagnosis of Antimicrobial Resistance.

Antimicrobial resistance (AMR) is a significant global health threat concern, necessitating healthcare practitioners to accurately prescribe the most effective antimicrobial agents with correct doses to combat resistant infections. This is necessary to improve the therapeutic outcomes for patients and prevent further increase in AMR. Consequently, there is an urgent need to implement rapid and sensitive clinical diagnostic methods to identify resistant pathogenic strains and monitor the efficacy of antimicrobials. In this study, we report a novel proof-of-concept magnetic scaffold-recombinase polymerase amplification (RPA) technique, coupled with an enzyme-linked oligonucleotide assay (ELONA) and surface-enhanced Raman scattering (SERS) detection, aimed at selectively amplifying and detecting the DNA signature of three resistant carbapenemase genes, VIM, KPC, and IMP. To achieve this, streptavidin-coated magnetic beads were functionalized with biotin-modified forward primers. RPA was conducted on the surface of the beads, resulting in an immobilized duplex amplicon featuring a single overhang tail specific to each gene. These tails were subsequently hybridized with recognition HRP probes conjugated to a complementary single-stranded oligonucleotide and detected colorimetrically. Additionally, they underwent hybridization with similar selective SERS probes and were measured using a handheld Raman spectrometer. The resulting quantification limits were at subpicomolar level for both assays, allowing the potential for early diagnosis. Moreover, we demonstrated the platform capability to conduct a multiplex RPA-SERS detection of the three genes in a single tube. Compared to similar approaches like PCR, RPA offers advantages of speed, affordability, and isothermal operation at 37 °C, eliminating the need for a thermal cycler. The whole assay was completed within <2 h. Therefore, this novel magnetic scaffold ELONA/SERS-RPA platform, for DNA detection, demonstrated excellent capability for the rapid monitoring of AMR in point-of-care applications, in terms of sensitivity, portability, and speed of analysis.

Complex dynamics of a magnetic microrobot driven by single deformation soft tail in random environment

This study focuses on exploring the complex dynamical behaviors of a magnetic microrobot in a random environment. The purpose is to reveal the mechanism of influence of random disturbance on microrobot dynamics. This paper establishes stochastic dynamic models for the microrobot before and after deformation, considering the influence of Gaussian white noise. The system responses are analyzed via steady-state probability density functions and first deformation time. The effects of different magnetic field strengths and fluid viscosities on the movement speed and angular velocity of the microrobot are studied. The results indicate that random disturbances can cause deformation of microrobots in advance compared to the deterministic case. This work contributes to the design and motion control of microrobots and enhances the theoretical foundation of microrobots.

Enhanced immunosuppressive capability of mesenchymal stem cell-derived small extracellular vesicles with high expression of CD73 in experimental autoimmune uveitis

BackgroundAutoimmune uveitis is an inflammatory disease triggered by an aberrant immune response. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) are emerging as potential therapeutic agents for this condition. CD73, an ectoenzyme present on MSC-sEVs, is involved in mitigating inflammation by converting extracellular adenosine monophosphate into adenosine. We hypothesize that the inhibitory effect of MSC-sEVs on experimental autoimmune uveitis (EAU) could be partially attributed to the surface expression of CD73.MethodsTo investigate novel therapeutic approaches for autoimmune uveitis, we performed lentiviral transduction to overexpress CD73 on the surface of MSC-sEVs, yielding CD73-enriched MSC-sEVs (sEVs-CD73). Mice with interphotoreceptor retinoid-binding protein (IRBP)-induced EAU were grouped randomly and treated with 50 µg MSC-sEVs, vector infected MSC-sEVs, sEVs-CD73 or PBS via single tail vein injection. We evaluated the clinical and histological features of the induced mice and analyzed the proportion and functional capabilities of T helper cells. Furthermore, T-cells were co-cultured with various MSC-sEVs in vitro, and we quantified the resulting inflammatory response to assess the potential therapeutic benefits of sEVs-CD73.ResultsCompared to MSC-sEVs, sEVs-CD73 significantly alleviates EAU, leading to reduced inflammation and diminished tissue damage. Treatment with sEVs-CD73 results in a decreased proportion of Th1 cells in the spleen, draining lymph nodes, and eyes, accompanied by an increased proportion of regulatory T-cells (Treg cells). In vitro assays further reveal that sEVs-CD73 inhibits T-cell proliferation, suppresses Th1 cells differentiation, and enhances Treg cells proportion.ConclusionOver-expression of CD73 on MSC-sEVs enhances their immunosuppressive effects in EAU, indicating that sEVs-CD73 has the potential as an efficient immunotherapeutic agent for autoimmune uveitis.

Thiosemicarbazone-benzenesulfonamide Derivatives as Human Carbonic Anhydrases Inhibitors: Synthesis, Characterization, and In silico Studies.

Carbonic anhydrases (CAs) are widespread metalloenzymes with the core function of catalyzing the interconversion of CO2 and HCO3 -. Targeting these enzymes using selective inhibitors has emerged as a promising approach for the development of novel therapeutic agents against multiple diseases. A series of novel thiosemicarbazone-containing derivatives were synthesized, characterized, and tested for their inhibitory activity against pharmaceutically important human CA I (hCA I), II (hCA II), IX (hCA IX), and XII (hCA XII) using the single tail approach. The compounds generally inhibited the isoenzymes at low nanomolar concentrations, with compound 6b having Ki values of 7.16, 0.31, 92.5, and 375 nM against hCA I, II, IX and XII, respectively. Compound 6e exhibited Ki values of 27.6, 0.34, 872, and 94.5 nM against hCA I, II, IX and XII, respectively. To rationalize the inhibition data, molecular docking studies were conducted, providing insight into the binding mechanisms, molecular interactions, and selectivity of the compounds towards the isoenzymes.

Xuebijing injection and its bioactive components alleviate nephrotic syndrome by inhibiting podocyte inflammatory injury

Xuebijing injection (XBJ) is widely used to treat nephrotic syndrome (NS) in clinic, but its bioactive components and therapeutic mechanism are still unclear. In this study, the bioactive components of XBJ were determined by ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS). The therapeutic effect of XBJ on NS was evaluated in BALB/c mice induced by adriamycin (ADR, 10 mg/kg) via a single tail vein. The protective effect of XBJ and its bioactive components on podocytes was demonstrated using mouse podocytes (MPC-5) induced by lipopolysaccharide (LPS, 4 μg/mL). The results show that 33 components of XBJ were identified. Furthermore, 12 bioactive components were detected in blood, including protocatechuic acid, salvianolic acid C, benzoyloxypaeoniflorin, danshensu, salvianolic acid A, salvianolic acid B, catechin, caffeic acid, galloylpaeoniflorin, oxypaeoniflorin, hydroxysafflor yellow A, rosmarinic acid. The relative content (%) of the bioactive components were 59.32, 16.01, 9.97, 9.73, 8.72, 8.31, 7.92, 6.54, 1.54, 1.30, 0.68 and 0.59 in this order. After XBJ treatment, the renal function, hyperlipidemia and renal pathological damage were improved in NS model mice. Moreover, the levels of nephrin and desmin which are functional proteins in podocytes were reversed, and the levels of pro-inflammatory factors were reduced by XBJ. Interestingly, protocatechuic acid and salvianolic acid C also showed good protective effects on podocyte function and reduced the level of inflammation in LPS-induced MPC-5. The study is the first time to elucidate the bioactive components of XBJ and its potential therapeutic mechanism for treating NS by protecting podocyte function.

Abstract 5975: Characterization and pharmacokinetics of ligand traps targeting the human epidermal growth factor receptor (HER) family

Abstract Antibodies targeting HER receptors have led to successful therapeutics for multiple human malignancies. Targeting the family of HER ligands provides an alternative strategy to inhibit signaling and subsequent proliferation of cancer cells. We have engineered ligand traps that bind the growth factors activating the HER family and have characterized a series of molecules (EN2000-Fc) using Surface Plasmon Resonance (SPR). Five distinct molecules were further evaluated for improved in vivo pharmacokinetics in mice that express human neonatal Fc receptor (FcRn). Mutations in the IgG Fc known to extend the in-vivo half-life of monoclonal antibodies were incorporated into the parental EN2000-Fc to generate 3 more distinct pan HER ligand traps. In addition, an EN2000-Fc variant with a full-length hinge was engineered, which is 5-amino-acid longer N-terminally than the parental molecule. These five molecules were synthesized (&amp;gt; 300 mg of each), purified (&amp;gt;98%), and characterized for in vitro and in vivo testing. Two variants were compared by evaluating the ligand binding affinity to 11 HER ligands using SPR. Both molecules showed comparable affinity against all ligands tested, confirming reproducibility of the pan HER ligand trap engineering technology. Among the ligands, HB-EGF had the highest affinity. High binding affinities to EGF, NRG1, NRG2, betacellulin and TGFα were also measured. The serum pharmacokinetics of the different ligand traps were compared in 6- to 8-week-old female C57BL/6 mice engineered to express human FcRn. Ligand traps were administered by single tail vein injection, and serum samples collected over a 28-day interval were analyzed by ELISA. Ligand traps with engineered Fc-mutations had 3- to 4-fold greater systemic exposure (area-under-the-curve) compared to ligand traps with the parental sequence, demonstrating improved in vivo characteristics of selected engineered fusion proteins. These results provide useful information for product candidate selection and for further preclinical development of a ligand trap targeting HER family receptors. Citation Format: Daniel C. Maneval, Cindy Yang, Cynthia Trevisiol, H. Michael Shepard, Pei Jin. Characterization and pharmacokinetics of ligand traps targeting the human epidermal growth factor receptor (HER) family [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5975.

Phospholipids with two polyunsaturated fatty acyl tails promote ferroptosis

Phospholipids containing a single polyunsaturated fatty acyl tail (PL-PUFA1s) are considered the driving force behind ferroptosis, whereas phospholipids with diacyl-PUFA tails (PL-PUFA2s) have been rarely characterized. Dietary lipids modulate ferroptosis, but the mechanisms governing lipid metabolism and ferroptosis sensitivity are not well understood. Our research revealed a significant accumulation of diacyl-PUFA phosphatidylcholines (PC-PUFA2s) following fatty acid or phospholipid treatments, correlating with cancer cell sensitivity to ferroptosis. Depletion of PC-PUFA2s occurred in aging and Huntington's disease brain tissue, linking it to ferroptosis. Notably, PC-PUFA2s interacted with the mitochondrial electron transport chain, generating reactive oxygen species (ROS) for initiating lipid peroxidation. Mitochondria-targeted antioxidants protected cells from PC-PUFA2-induced mitochondrial ROS (mtROS), lipid peroxidation, and cell death. These findings reveal a critical role for PC-PUFA2s in controlling mitochondria homeostasis and ferroptosis in various contexts and explain the ferroptosis-modulating mechanisms of free fatty acids. PC-PUFA2s may serve as diagnostic and therapeutic targets for modulating ferroptosis.

AAV-Mediated Delivery of Plakophilin-2a Arrests Progression of Arrhythmogenic Right Ventricular Cardiomyopathy in Murine Hearts: Preclinical Evidence Supporting Gene Therapy in Humans.

Pathogenic variants in PKP2 (plakophilin-2) cause arrhythmogenic right ventricular cardiomyopathy, a disease characterized by life-threatening arrhythmias and progressive cardiomyopathy leading to heart failure. No effective medical therapy is available to prevent or arrest the disease. We tested the hypothesis that adeno-associated virus vector-mediated delivery of the human PKP2 gene to an adult mammalian heart deficient in PKP2 can arrest disease progression and significantly prolong survival. Experiments were performed using a PKP2-cKO (cardiac-specific, tamoxifen-activated PKP2 knockout murine model). The potential therapeutic, adeno-associated virus vector of serotype rh.74 (AAVrh.74)-PKP2a (PKP2 variant A; RP-A601) is a recombinant AAVrh.74 gene therapy viral vector encoding the human PKP2 variant A. AAVrh.74-PKP2a was delivered to adult mice by a single tail vein injection either before or after tamoxifen-activated PKP2-cKO. PKP2 expression was confirmed by molecular and histopathologic analyses. Cardiac function and disease progression were monitored by survival analyses, echocardiography, and electrocardiography. Consistent with prior findings, loss of PKP2 expression caused 100% mortality within 50 days after tamoxifen injection. In contrast, AAVrh.74-PKP2a-mediated PKP2a expression resulted in 100% survival for >5 months (at study termination). Echocardiographic analysis revealed that AAVrh.74-PKP2a prevented right ventricle dilation, arrested left ventricle functional decline, and mitigated arrhythmia burden. Molecular and histological analyses showed AAVrh.74-PKP2a-mediated transgene mRNA and protein expression and appropriate PKP2 localization at the cardiomyocyte intercalated disc. Importantly, the therapeutic benefit was shown in mice receiving AAVrh.74-PKP2a after disease onset. These preclinical data demonstrate the potential for AAVrh.74-PKP2a (RP-A601) as a therapeutic for PKP2-related arrhythmogenic right ventricular cardiomyopathy in both early and more advanced stages of the disease.

Characterization of $ Q $ graph by the burning number

&lt;abstract&gt;&lt;p&gt;The burning number $ b(G) $ of a graph $ G $, introduced by Bonato, is the minimum number of steps to burn the graph, which is a model for the spread of influence in social networks. In 2016, Bonato et al. studied the burning number of paths and cycles, and based on these results, they proposed a conjecture on the upper bound for the burning number. In this paper, we determine the exact value of the burning number of $ Q $ graphs and confirm this conjecture for $ Q $ graph. Following this, we characterize the single tail and double tails $ Q $ graph in term of their burning number, respectively.&lt;/p&gt;&lt;/abstract&gt;

Dysfunctional Stromal Pathways Mark Early Changes within the Bone Marrow Microenvironment in JAK2 V617F-Driven Model of Myeloproliferative Neoplasm

Background: JAK2V617F (JAK2VF) is the primary driver mutation in classical myeloproliferative neoplasms (MPN). JAK2VF is present decades prior to diagnosis (Mitchell et.al. Nature 2022), and the JAK2VF+ clone may remodel the BM microenvironment further supporting its expansion (Curto-Garcia, et. al. Haematologica 2020). Understanding this relationship, particularly during early disease development may aid identification of new therapeutic targets to stop or revert these early changes. Human BM procured before MPN diagnosis is rarely available and most murine MPN models use myeloablative conditioning (eg., irradiation), permanently altering the BM stroma (Costa &amp; Reagan Frontiers 2019), diminishing the clinical relevance of resultant findings. We developed an innovative translatable model of MPN with sustainable low-level disease engraftment and no requirement for recipient conditioning. By preserving the normal microenvironment, our model enabled detection of early changes within the BM stroma induced by the JAK2VF+ clone. Methods: Whole BM transplantation (BMT) was performed via a single tail vein injection into unconditioned C57BL/6 Ptprc a (JAX#002014, CD45.1+) recipient mice. Donor animals consisted of either wildtype ( wt) C57BL/6 (JAX#000664) mice or our PolyI:C inducible MPN-like model created by crossing a floxed-JAK2VF (JAX#031658) with Mx1-Cre (JAX#003556) animals (JAK2VF Parental). For all BMTs, donors and recipients were age- (10wks) and sex-matched. BMT cell concentrations ranged from 1e6 to 15e6per injection, n≥10 mice, both sexes were used per group. A cohort of non-BMT age- and sex-matched recipients were maintained as naïve controls. Recipient serial submandibular blood collections were used to examine complete blood cell counts and donor chimerism. Bulk RNA-seq transcriptomic analysis was performed on digested and lineage-negative sorted whole BM from matched naïve and 5e6 BMT recipients (n=7 and 6, respectively) to delineate stromal alterations driven by JAK2VF+ MPN clone. Qualitative x-ray analysis was performed on femurs. Results: 15e6 wt donor CD45.2 BM cells can be transplanted sustainably into unconditioned CD45.1 recipients with ~3.0% donor chimerism, maintained up to 200-days post-BMT (Fig A). Follow up secondary BMT into conditioned recipients using as few as 25e4CD45.2+ cells sorted from primary BMT recipients displayed 83% average engraftment by 150-day post BMT, confirming functional wt donor CD45.2 HSC. This successful strategy was used to perform BMT using JAK2VF parental (1e6, 5e6, and 15e6) cells. Detected chimerism followed a dose response, not exceeding an average of 10% up to &amp;gt;225 days. Surprisingly, with the engraftment at &amp;lt;10%, we observed MPN-like phenotype (elevated hemoglobin and monocytosis) except for no thrombocytosis (Fig A). To identify alterations in the BM niche, stromal cells were isolated from BMT recipients and subjected to RNA-seq. Enrichment of stromal cells was validated by confirming that 23% of the top 100 highest read coverage transcripts were encoding stromal genes (i.e. Sparc, Dcn, Col2a1, and Cxcl12). Gene set enrichment analysis (GSEA) of stromal fraction showed upregulation of osteoclastic differentiation and bone remodeling. GSEA against hallmark gene sets indicated upregulation of mesenchymal phenotype and inflammatory response suggesting an underlying effect on the stroma driven by the presence of the JAK2VF clone. Qualitative x-ray of femurs indicated loss of bone density, suggesting disease-driven effect on the stroma (Fig B). Discussion: The development of our translatable model of MPN, where a small subset of cells drives the disease within unconditioned recipients represents an important milestone towards studying early disease pathology in MPNs. Using wt BMT, we demonstrated the successful establishment of long-term, low-level chimerism in unconditioned recipients. We found the clone-dependent impact on the stroma without myeloablative conditioning. Bulk transcriptomics and femur x-rays indicate aberrant bone morphology in BMT mice, despite the low level of engraftment (&amp;lt;5%) in the recipient system. Our data suggests that even low VAF of JAK2VF may support pathologic remodeling of the BM environment, warranting further exploration of patient BM niche early and late in the MPN course.

Stimulation of ATP Hydrolysis by ssDNA Provides the Necessary Mechanochemical Energy for G4 Unfolding

The G-quadruplex (G4) is a distinct geometric and electrophysical structure compared to classical double-stranded DNA, and its stability can impede essential cellular processes such as replication, transcription, and translation. This study focuses on the BsPif1 helicase, revealing its ability to bind independently to both single-stranded DNA (ssDNA) and G4 structures. The unfolding activity of BsPif1 on G4 relies on the presence of a single tail chain, and the covalent continuity between the single tail chain and the G4′s main chain is necessary for efficient G4 unwinding. This suggests that ATP hydrolysis-driven ssDNA translocation exerts a pull force on G4 unwinding. Molecular dynamics simulations identified a specific region within BsPif1 that contains five crucial amino acid sites responsible for G4 binding and unwinding. A “molecular wire stripper” model is proposed to explain BsPif1′s mechanism of G4 unwinding. These findings provide a new theoretical foundation for further exploration of the G4 development mechanism in Pif1 family helicases.

A multiobjective optimization approach for threshold determination in extreme value analysis for financial time series

The literature on the extreme value theory threshold optimization problem for multiple time series analysis does not consider determining a single optimal tail probability for all marginal distributions. With multiple tail probabilities, their discrepancy results in a differing number of exceedances, which may favour a particular marginal series. In this study, we propose a single optimal tail probability by integrating trade-offs among multiple time series within an MOO framework. Mathematically, our approach links the peaks-over-threshold technique and goal programming technique by developing a set of regression functions, which represent continuous paths of possible tail areas for multiple time series, and we formulate them at the desired levels within a multiobjective optimization framework. The optimal solution is found as the minimum Chebyshev variant weighted value. Our approach advances the development of the peaks-over-threshold method by considering the characteristics of a group of time series collectively instead of independently. The proposed optimal tail probability can be considered an optimal reference point for practical risk investment portfolio analysis that employs an identical tail size across multiple time series data. The daily log returns of four U.S. stock market indices, namely, S&P 500, NASDAQ Composite, NYSE Composite, and Russell 2000, from 1 July 1992 to 30 June 2022 are studied empirically.

Investigation of the Metabolism of Astragaloside IV in a Puromycin-Damaged Rat Model by UPLC-Q-TOF-MS/MS Analysis.

Astragaloside IV (AS-IV) has been shown to provide renal protection in various kidney injury models. However, the metabolic profile variation of AS-IV in pathological models in vivo is not well established. This study aims to explore the metabolic pathway of AS-IV in vivo in the classical puromycin aminonucleoside (PAN)-induced kidney injury in a rat model. Twelve Wistar rats were randomly divided into the AS-IV (CA) and the PAN+AS-IV (PA) treatment groups. PAN was injected by a single tail intravenous (i. v.) injection at 5 mg/100 g body weight, and AS-IV was administered intragastrically (i. g.) at 40 mg/kg for 10 days. Fecal samples of these rats were collected, and metabolites of AS-IV were detected by ultra-performance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) to explore the AS-IV metabolic pathway. The metabolic differences between the AS-IV and PAN+AS-IV groups were compared. A total of 25 metabolites were detected, and deglycosylation, deoxygenation, and methyl oxidation were found to be the main metabolic pathways of AS-IV in vivo. The abundance of most of these metabolites in the PAN+AS-IV group was lower than that in the AS-IV treatment group, and differences for seven of them were statistically significant. Our study indicates that AS-IV metabolism is affected in the PAN-induced kidney injury rat model.

A Morphometric Study Analyzing the Anterior Epidural Space Volume Throughout Childhood

BACKGROUND: Following disc herniations, fragments migrate into the anterior epidural space within the lumbar spine. Although the volume of this area has been previously described in the adult population, the volume is relatively unknown within children. OBJECTIVES: Investigate the relative volume in the lumbar anterior epidural space within the growing spine by using imaging studies. STUDY DESIGN: Retrospective chart review. SETTING: University Medical Center in Lubbock Texas. A teaching hospital affiliated with Texas Tech University Health Sciences Center. METHODS: We conducted a retrospective review of the charts of pediatric patients seen at our institution from 2018 through 2020. Charts chosen for our investigation contained computed tomography imaging of the lumber spine, showing no deformities. Thirty patients were stratified equally among 3 age groups, 2-5 years old, 10-12 years old, and 16-18 years old. The anterior epidural space was measured in each patient 3 times using the previously reported method used by Teske et al (1). Results were compared with a combination of analysis of variance (ANOVA) and single tail paired t test. RESULTS: There was a statistically significant difference in the anterior epidural space size among age groups at all levels of the lumbar spine. When comparing only 2 groups together, the younger age group had anterior epidural space sizes significantly smaller than the other age group for all levels of the lumbar spine. The 10-12 age group had a significantly smaller space in the anterior epidural space than the 16–18-year olds only at the level of L2, L4, and L5 (P = 0.048,0.039, and 0.031, respectively). Within the 16–18-year age group, the anterior epidural space was significantly different between L4 and L3 and L2 and L3 (P &lt; 0.001 and P = 0.019, respectively). LIMITATIONS: Our study is limited by its retrospective nature and the sample size of the patient groups. Furthermore, the use of computed tomography imaging and not making physical measurements limits our accuracy. CONCLUSION: The volume of the anterior epidural space is smaller in the pediatric population than the adult population. The inability of herniated discs to fit within the epidural space in children and adolescents could potentially be the cause of the increased failure of conservative treatment for pediatric lumbar disc herniations. KEY WORDS: Anterior epidural space, lumbar herniated disc, low back pain, fossa corporis vertebralis dorsalis, free disc fragment, lumbar spine anatomy

Trichinella spiralis-Secreted Products Promote Collagen Capsule Formation through TGF-β1/Smad3 Pathway.

Trichinella spiralis (T. spiralis) muscle larvae colonize in the host's skeletal muscle cells, which are surrounded by collagen capsules. The mechanism underlying muscle stage larva-induced collagen capsule formation remains unknown. To clarify the mechanism, a T. spiralis muscular-infected mouse model was established by a single lateral tail vein injection with 20,000 T. spiralis newborn larvae (NBL). The infected mice were treated with or without SB525334 (TGF-β1 receptor type I inhibitor). Diaphragms were obtained post-infection, and the expression levels of the TGF-β1/Smad3 pathway-related genes and collagen genes (type IV and VI) were observed during the process of collagen capsule formation. The changes in myoblasts under stimulation of the excretory-secretory (ES) products of NBL with or without SB525334 were further investigated. Results showed that the expression levels of type IV collagen gene, type VI collagen gene, Tgfb1, and Smad3 were significantly increased in infected mice muscle cells. The expression levels of all the above genes were enhanced by the products of NBL in myoblast cells. These changes were reversed by co-treatment with SB525334 in vivo and in vitro. In conclusion, the TGF-β1/Smad3 pathway can be activated by T. spiralis infection in muscle cells. The activated TGF-β1/Smad3 pathway can stimulate the secretion of collagens by myocytes and plays a promoting role in the process of collagen capsule formation. The research has the limitation that the protein identification of the products of NBL has yet to be performed. Therefore, the specific components in the T. spiralis ES products that induce collagen synthesis should be further investigated.

Subconjunctival injection of human umbilical cord mesenchymal stem cells alleviates experimental allergic conjunctivitis via regulating T cell response

BackgroundT helper 2 (Th2) cells are thought to play critical roles in allergic conjunctivitis (AC). They release inflammatory cytokines to promote an allergic response in AC. Due to individual heterogeneity and long-term chronic management, current therapies do not always effectively control AC. Mesenchymal stem cells (MSCs) have been shown to be effective in treating allergy-related disorders, but it is unclear how exactly the Th2-mediated allergic response is attenuated. This study aims to elucidate the therapeutic effect and mechanism of the human umbilical cord MSCs (hUCMSCs) in a mouse model of experimental AC (EAC).MethodsA mouse EAC model was established by inoculating short ragweed (SRW) pollen. After the SRW pollen challenge, the mice received a single subconjunctival or tail vein injection of 2 × 106 hUCMSCs, or subconjunctival injection of hUCMSCs conditioned medium (hUCMSC-CM), and dexamethasone eye drops was used as positive control; subsequent scratching behavior and clinical symptoms were assessed. Immunostaining and flow cytometry were carried out to show allergic reactions and the activation of CD4 + T cell subsets in the conjunctiva and cervical lymph nodes (CLNs). Gene expression was determined by RNA-seq and further verified by qRT-PCR and Western blot. Co-culture assays were performed to explore the regulatory role of hUCMSCs in the differentiation of CD4 + naive T cells (Th0) into Th2 cells.ResultsSubconjunctival administration of hUCMSCs resulted in fewer instances of scratching and lower inflammation scores in EAC mice compared to the tail vein delivery, hUCMSC-CM and control groups. Subconjunctival administration of hUCMSCs reduced the number of activated mast cells and infiltrated eosinophils in the conjunctiva, as well as decreased the number of Th2 cells in CLNs. After pretreatment with EAC mouse serum in vitro to mimic the in vivo milieu, hUCMSCs were able to inhibit the differentiation of Th0 into Th2 cells. Further evidence demonstrated that repression of Th2 cell differentiation by hUCMSCs is mediated by CRISPLD2 through downregulation of STAT6 phosphorylation. Additionally, hUMCSCs were able to promote the differentiation of Th0 cells into regulatory T cells in CLNs of EAC mice.ConclusionsSubconjunctival injection of hUCMSCs suppressed the Th2-allergic response and alleviated clinical symptoms. This study provides not only a potential therapeutic target for the treatment of AC but also other T cell-mediated diseases.

Ferroptosis is involved in passive Heymann nephritis in rats

Ferroptosis is found to be involved in some experimental models of kidney diseases, but its role in membrane nephropathy (MN) is still unclear. The purpose of this study is to explore whether ferroptosis occurred in MN, and the role of ferritinophagy. In this study, passive Heymann nephritis (PHN) rats were induced by single tail vein injection of anti-Fx1A serum, and normal rats were used as control. The changes of 24 h urinary protein, serum biochemical parameters, renal pathological damage, iron content, lipid peroxidation parameters, ferroptosis markers, and ferritinophagy markers were evaluated in the two groups. Compared with the control group, PHN rats showed obvious proteinuria, hypoproteinemia, and hyperlipidemia. Besides, more severe renal pathological damage and higher Fe2+ levels were observed in PHN rats, and the levels of malondialdehyde (MDA) increased significantly, while the levels of superoxide Dismutase (SOD) and glutathione (GSH) decreased. In addition, the expression of glutathione peroxidase 4 (GPX4) in renal tissues of PHN rats decreased significantly, while the expression of transferrin receptor (TFR) and acyl-CoA synthetase long-chain family member 4 (ACSL4) increased. The expression of microtubule associated protein 1 light chain 3 (LC3) II/LC3I and nuclear receptor coactivator 4 (NCOA4) increased significantly. Therefore, our study shows that ferroptosis is involved in the pathological damage of MN, and companied by activation of ferritinophagy.

Links between US and Turkish agricultural commodity Markets: Nonlinear dependence and tail risk

In these unprecedented times, marred by the effects of the Covid-19 pandemic, global warming, and the war in Ukraine that began in February 2022, new approaches such as tail dependence have attracted more interest than conventional market dependence methodologies in analyzing time series in order to evaluate market linkage. In this study, we use the tail-restricted integrated regression function (IRF), introduced as a new methodology for nonlinear tail-mean dependence analysis. The IRF approach has several advantages over the existing tail-dependence measures focused solely on the occurrence of single tail events. To examine market dependence and tail risk, we analyze the nexus between the US and Turkish agricultural commodity markets over the period January 5, 2016–May 31, 2022. In addition to the daily prices of barley, corn, and wheat on agricultural commodity markets, we use Brent oil as a representative for the energy market, interest, and foreign exchange rates for financial markets as variables in our study. The results of upside and downside asymmetric risk spillovers show the direction of impact from the US agricultural market to the Turkish agricultural market. The findings suggest that, following the launch of a spot market in Türkiye, the launch of an agricultural commodity futures market will enhance the completeness and the link between the spot and derivatives markets there.