Impact of low-to moderate-intensity exercise training on the mRNA expression of purine receptors across various vessels in SHR.

OBJECTIVE: In this study, we developed an exercise training protocol for assessing both blood pressure dynamics and mRNA expression levels of purine receptors in various vascular tissues during physical activity. The objective is to assess the impact of exercise training on blood pressure regulation in spontaneously hypertensive rats (SHR) and purine receptors in vascular tissues. METHODS: Wistar Kyoto (WKY) and SHR rats were randomly allocated into sedentary (Sed) and exercise training (ExT) groups. Rats in the Sed groups were allowed unrestricted movement, whereas those in the ExT groups underwent a 16-week regimen of low- to moderate-intensity treadmill exercise. Throughout the intervention period, blood pressure measurements and body weight recordings were conducted. Additionally, mRNA expressions of purine receptors P2X1, P2Y1, and P2Y2 in renal artery (RA), internal carotid artery (Int), thoracic aorta (Aor), and caudal artery (Cau) tissues were assessed. RESULTS: In the Sed group, body weight of SHR rats was observed to be lower compared to the three other groups. Over the course of the exercise regimen, blood pressure in the ExT group of SHR rats reduced gradually, converging towards levels similar to those observed in WKY rats by the conclusion of the exercise period. Regarding mRNA expression patterns of P2X1 receptors across the four blood vessels, WKY and SHR rats demonstrated similar sequences, consistently displaying the highest expression levels in the Cau. Conversely, mRNA expressions of P2Y1 and P2Y2 receptors exhibited distinct sequences across the four blood vessels in both WKY and SHR rats. Notably, compared to the Sed group of WKY rats, mRNA expression of P2X1 receptor in the Int of SHR rats revealed an increase, while expressions in the Aor of WKY rats and the Cau of SHR rats decreased following exercise. Expression of P2Y1 receptor mRNA decreased across all four types of blood vessels in SHR rats. Post-exercise, P2Y1 receptor mRNA expression increased in the Aor, decreased in the Cau of WKY rats, and increased in the Int and renal artery (RA) of SHR rats. Conversely, expressions of P2Y2 receptor mRNA decreased in the Int and Aor of SHR rats. Except for the Aor of WKY rats, expressions of P2Y2 receptor mRNA increased in the other arteries of both rat types following exercise. CONCLUSION: Differences in the distribution of purine receptor subtypes among distinct arterial segments in both WKY and SHR rats were observed. Exercise training was found to enhance mRNA expression levels of P2Y receptors in these rat models. This finding implies that exercise training might reduce hypertension in SHR rats by bolstering the purinergic relaxation response.

Metal Ion Modulated Electron Transfer in Metalloviologen Compounds: Photochromism and Differentiable Amine Detection.

Different types of electron transfers (ETs) underlie the versatile use of various solid viologen-derived compounds, which is still insufficiently understood and difficult to control. Here, we demonstrate an effective strategy for modulating the key ET process in crystalline metalloviologen compounds (MVCs). By adjusting the coordinated transition metal ions bearing different electronic structures (e.g., d5, d7, d10), three MVCs (i.e., Mn-1, Co-2, and Cd-3) with highly consistent coordination environments have been synthesized successfully. Surprisingly, whether the photochromism (energy-induced ET mechanism) or the specific analyte recognition (molecule-induced ET mechanism), compound Cd-3 exhibits obvious photochromic behavior and differential dimethylamine detection. Combined detailed structural analysis with theoretical calculations, such unique ion-dependent properties, were correlated to the fine modulation of the electron density of the bipyridinium cores by metal ions. Additionally, thanks to the delicate recognition of dimethylamine vapor, a convenient test strip Cd-3-PAN was prepared as a sensitive biogenic amine sensor for evaluating the real-time freshness of seafood.

Piperidine-based ionic liquid additive with electrostatic shielding and redox activity enabling advanced lithium-oxygen batteries.

Here, we propose a piperidine-based ionic liquid additive. The electrostatic shielding effect of the piperidine cation (PP13+) effectively inhibits the growth of lithium dendrites. Simultaneously, the redox activity of the bromine anion synergistically reduces the overpotential. This approach significantly improves the cycling performance of lithium-oxygen batteries.

Danggui-Shaoyao-San protects against non-alcoholic steatohepatitis via modulation of hepatic APP protein, Lysosomal CTSB release, and NF-κB activation.

Background: Non-alcoholic steatohepatitis (NASH), an escalating global health concern, is a primary factor behind cirrhosis, liver transplantation, and hepatocellular carcinoma. Effective treatments remain elusive. Danggui-Shaoyao-San (DGSY), a classic famous prescription employed in treating NASH, could hold promise, although its molecular underpinnings are still under investigation. This study undertakes an exploration of the impacts of DGSY on NASH and seeks to illuminate the mechanisms at play. Methods: UHPLC-Q-Orbitrap HRMS was employed to identify compounds within DGSY. Mice underwent a 25-week regimen of HFHC diet and high-sugar water, with 4 weeks of DGSY treatment for efficacy and pathogenic mechanism exploration in vivo. L02 cells were cultured with 0.2 mM FFA for 24 h, exposed to DGSY at 1 mg/ml and 2 mg/ml for efficacy and pathogenic mechanism exploration in vitro. Using online databases, we sought potential targets for NASH treatment, and through PPI networks, identified key targets. Expression levels of genes and proteins were examined by western blotting, RT-PCR, and immunofluorescence staining. Results: Thirty-four compounds were identified within DGSY. DGSY brought about marked reductions in biochemical indicators and yielded significant improvements in NASH mice histological features. Additionally, it mitigated hepatic steatosis and inflammation both in vivo and in vitro. The top 10 targets from two network pharmacology analyses, one focusing on structural prediction and the other on literature mining, identified APOE and APP as potential therapeutic targets for DGSY in NASH treatment. PCR validation confirmed that DGSY reduced APP expression after treatment, and further investigation revealed that DGSY significantly suppressed hepatic APP and Aß expression, indicating its effectiveness in treating NASH. Furthermore, it inhibited Aß-induced Cathepsin B lysosomal release, reducing hepatic inflammation. Conclusion: Danggui-Shaoyao-San has anti-steatohepatitis effects in ameliorating hepatic APP protein expression, reducing hepatic lysosomal CTSB release, and suppressing hepatic NF-κB activation. The study provided a more theoretical basis for the future clinical application of DGSY.

Synergistic impact of plasma albumin and cognitive function on all-cause mortality in Chinese older adults: a prospective cohort study.

Background: Hypoalbuminemia and cognitive impairment (CI) each independently increase the mortality risk in older adults. However, these two geriatric syndromes can occur simultaneously. In community-dwelling older adults, is the combination of hypoalbuminemia and CI linked to a higher mortality risk than either condition alone? Objective: We aimed to investigate the association between plasma albumin, cognitive function, and their synergistic effect on mortality in Chinese community-dwelling older adults. Methods: Data from the Chinese Longitudinal Healthy Longevity Survey (2012) included 1,858 participants aged ≥65. Baseline assessments comprised albumin levels and cognitive status. All-cause mortality was confirmed through 2014-2018 surveys. Cox proportional hazards models assessed associations, and restricted cubic splines explored albumin-mortality relationship. Results: During a median follow-up of 48.85 months, 921 deaths. Albumin≥35 g/L vs < 35g/L [HR: 1.33 (95%CI, 1.10, 1.62)] and CI vs normal cognition [HR: 1.69 (95%CI, 1.43, 1.99)] independently predicted mortality. A dose-response relationship with mortality was observed for albumin quartiles (p < 0.001). Each SD increase in MMSE or albumin correlated with 22% and 15% lower mortality risk, respectively. Combined hypoproteinemia and CI increased the mortality risk by 155%, with a notably higher risk in males, those aged <85 years, and individuals living in rural areas. Interaction effects of albumin and CI on mortality were observed (p < 0.001). In the single CI group, older adults had a 61% increased risk of mortality in the hypoproteinaemia group compared with the albumin-normal group. Restricted cubic spline revealed a reverse J-shaped association, particularly for participants without CI. For individuals with CI, albumin levels were inversely associated with mortality risk. Conclusion: Hypoproteinemia and CI, individually and combined, increased all-cause mortality risk in Chinese older adults, with stronger effects observed in males, younger older adults, and those living in rural areas. These findings emphasize the importance of targeted adjustments and early nutrition programs in health prevention and clinical care for older adults.

Signals from intestinal microbiota mediate the crosstalk between the lung-gut axis in an influenza infection mouse model.

Introduction: Introduction: The influenza virus primarily targets the respiratory tract, yet both the respiratory and intestinal systems suffer damage during infection. The connection between lung and intestinal damage remains unclear. Methods: Our experiment employs 16S rRNA technology and Liquid Chromatography-Mass Spectrometry (LC-MS) to detect the impact of influenza virus infection on the fecal content and metabolites in mice. Additionally, it investigates the effect of influenza virus infection on intestinal damage and its underlying mechanisms through HE staining, Western blot, Q-PCR, and flow cytometry. Results: Our study found that influenza virus infection caused significant damage to both the lungs and intestines, with the virus detected exclusively in the lungs. Antibiotic treatment worsened the severity of lung and intestinal damage. Moreover, mRNA levels of Toll-like receptor 7 (TLR7) and Interferon-b (IFN-b) significantly increased in the lungs post-infection. Analysis of intestinal microbiota revealed notable shifts in composition after influenza infection, including increased Enterobacteriaceae and decreased Lactobacillaceae. Conversely, antibiotic treatment reduced microbial diversity, notably affecting Firmicutes, Proteobacteria, and Bacteroidetes. Metabolomics showed altered amino acid metabolism pathways due to influenza infection and antibiotics. Abnormal expression of indoleamine 2,3-dioxygenase 1 (IDO1) in the colon disrupted the balance between helper T17 cells (Th17) and regulatory T cells (Treg cells) in the intestine. Mice infected with the influenza virus and supplemented with tryptophan and Lactobacillus showed reduced lung and intestinal damage, decreased Enterobacteriaceae levels in the intestine, and decreased IDO1 activity. Discussion: Overall, influenza infection caused damage to lung and intestinal tissues, disrupted intestinal microbiota and metabolites, and affected Th17/Treg balance. Antibiotic treatment exacerbated these effects. Supplementation with tryptophan and Lactobacillus improved lung and intestinal health, highlighting a new understanding of the lung-intestine connection in influenza-induced intestinal disease.

[Multi-objective Identification Method for Influencing Factors of Soil Heavy Metal Content Change].

Identifying the influencing factors of soil heavy metal content changes is the basis for reducing or preventing soil heavy metal pollution. Taking an agricultural experimental field in Changping District of Beijing as an example, the heavy metal content changes in As, Cr, Cu, Ni, Pb, and Zn from 2012 to 2022 were firstly analyzed. Secondly, the influencing factors of the heavy metal content changes were detected based on the geographical detector at the single-target and multi-target levels, respectively. Finally, comparative experiments with the correlation analysis method and existing studies were set up to evaluate the effectiveness of the identification method of influencing factors developed in this study. The results showed that human activity factors have exacerbated the changes in soil heavy metal content in the study area as follows： ① At the single-target level, the land use type was the main influencing factor on the changes in Cr, Cu, and Zn contents, and the annual deposition flux influenced the changes in As. The results of the interaction detection showed that there was an enhancement effect among the factors, and the interaction of the human activity factors dominated for the factor identification. ② The results of the multi-target level detection covered the results of the single-target level detection, which could identify more influencing factors. The land use type affected the changes in Cu, Zn, Cr, Ni, and As, and the changes in As and Zn were influenced by the annual deposition fluxes. ③ The multi-target identification method coupled with geographical detector and principal component analysis could effectively identify the influencing factors of soil heavy metal content changes, which was much more effective than the single soil heavy metal correlation method. The developed multi-target identification method for influencing factors of heavy metal content changes can provide technical support for the regional pollution monitoring and macro-management of soil heavy metals.

[Advances in Research of the Effects and Mechanisms of Polyethylene Microplastics on Soil Nitrogen Transformation].

In the agricultural lands of China, polyethylene is the main component of microplastics （MPs）, with characteristics such as small size, wide distribution, easy accumulation, and difficult degradation. Therefore, it may have an impact on the elemental cycling process of the soil. On the basis of reviewing the key literatures in the past few years, this study systematically analyzed and summarized the key factors and processes of the polyethylene microplastics （PE-MPs） affecting soil nitrogen transformation. On the one hand, PE-MPs directly affected the activities of microorganisms and key enzymes related to soil nitrogen transformation by enriching microorganisms, selecting colonized microbial populations, and releasing additives. On the other hand, PE-MPs had indirect impacts on the activities of microorganisms and key enzymes related to soil nitrogen transformation by affecting soil physicochemical properties of soil and changing the microenvironment for microbial growth. Moreover, phthalates, an important additive of the MPs, may be the key factor affecting soil nitrogen transformation in the short-term. Finally, we posed key scientific issues that should be further studied in order to provide scientific support for nitrogen nutrition regulation and ecological risk assessment of soils contaminated by PE-MPs.

Effects of H9N2 avian influenza virus infection on metabolite content and gene expression in chick DF1 cells.

After viral infection, the virus relies on the host cell's complex metabolic and biosynthetic machinery for replication. However, the impact of avian influenza virus (AIV) on metabolites and gene expression in poultry cells remains unclear. To investigate this, we infected chicken embryo fibroblasts DF1 cells with H9N2 AIV at an MOI of 3. Our aim was to explore how H9N2 AIV alters DF1 cells metabolic pathways to facilitate its replication. We employed metabolomics and transcriptomics techniques to analyze changes in metabolite content and gene expression. Metabolomics analysis revealed a significant increase in glutathione-related metabolites, including reduced glutathione (GSH), oxidized glutathione (GSSG) and total glutathione (T-GSH) upon H9N2 AIV infection in DF1 cells. Elisa results confirmed elevated levels of GSH, GSSG, and T-GSH consistent with metabolomics findings, noting a pronounced increase in GSSG compared to GSH. Transcriptomics showed significant alterations in genes involved in glutathione synthesis and metabolism post-H9N2 infection. However, adding the glutathione synthesis inhibitor BSO exogenously significantly promoted H9N2 replication in DF1 cells. This was accompanied by increased mRNA levels of pro-inflammatory cytokines (IL-1ß, IFN-γ) and decreased mRNA levels of anti-inflammatory cytokines (TGF-ß, IL-13). BSO also reduced catalase (CAT) gene expression and inhibited its activity, leading to higher reactive oxygen species (ROS) and malondialdehyde (MDA) level in DF1 cells. qPCR results indicated decreased mRNA levels of Nrf2, NQO1, and HO-1 with BSO, ultimately increasing oxidative stress in DF1 cells. Therefore, the above results indicated that H9N2 AIV infection in DF1 cells activated the glutathione metabolic pathway to enhance the cell's self-defense mechanism against H9N2 replication. However, when GSH synthesis is inhibited within the cells, it leads to an elevated oxidative stress level, thereby promoting H9N2 replication within the cells through Nrf2/HO-1 pathway. This study provides a theoretical basis for future rational utilization of the glutathione metabolic pathway to prevent viral replication.

Antisense oligonucleotides enhance SLC20A2 expression and suppress brain calcification in a humanized mouse model.

Primary familial brain calcification (PFBC) is a genetic neurological disease, yet no effective treatment is currently available. Here, we identified five novel intronic variants in SLC20A2 gene from six PFBC families. Three of these variants increased aberrant SLC20A2 pre-mRNA splicing by altering the binding affinity of splicing machineries to newly characterized cryptic exons, ultimately causing premature termination of SLC20A2 translation. Inhibiting the cryptic-exon incorporation with splice-switching ASOs increased the expression levels of functional SLC20A2 in cells carrying SLC20A2 mutations. Moreover, by knocking in a humanized SLC20A2 intron 2 sequence carrying a PFBC-associated intronic variant, the SLC20A2-KI mice exhibited increased inorganic phosphate (Pi) levels in cerebrospinal fluid (CSF) and progressive brain calcification. Intracerebroventricular administration of ASOs to these SLC20A2-KI mice reduced CSF Pi levels and suppressed brain calcification. Together, our findings expand the genetic etiology of PFBC and demonstrate ASO-mediated splice modulation as a potential therapy for PFBC patients with SLC20A2 haploinsufficiency.

Adeno-Associated Virus Engineering and Load Strategy for Tropism Modification, Immune Evasion and Enhanced Transgene Expression.

Gene therapy aims to add, replace or turn off genes to help treat disease. To date, the US Food and Drug Administration (FDA) has approved 14 gene therapy products. With the increasing interest in gene therapy, feasible gene delivery vectors are necessary for inserting new genes into cells. There are different kinds of gene delivery vectors including viral vectors like lentivirus, adenovirus, retrovirus, adeno-associated virus et al, and non-viral vectors like naked DNA, lipid vectors, polymer nanoparticles, exosomes et al, with viruses being the most commonly used. Among them, the most concerned vector is adeno-associated virus (AAV) because of its safety, natural ability to efficiently deliver gene into cells and sustained transgene expression in multiple tissues. In addition, the AAV genome can be engineered to generate recombinant AAV (rAAV) containing transgene sequences of interest and has been proven to be a safe gene vector. Recently, rAAV vectors have been approved for the treatment of various rare diseases. Despite these approvals, some major limitations of rAAV remain, namely nonspecific tissue targeting and host immune response. Additional problems include neutralizing antibodies that block transgene delivery, a finite transgene packaging capacity, high viral titer used for per dose and high cost. To deal with these challenges, several techniques have been developed. Based on differences in engineering methods, this review proposes three strategies: gene engineering-based capsid modification (capsid modification), capsid surface tethering through chemical conjugation (surface tethering), and other formulations loaded with AAV (virus load). In addition, the major advantages and limitations encountered in rAAV engineering strategies are summarized.

Performances of a novel BAF with ferromanganese oxide modified biochar (FMBC) as the carriers for treating antibiotics, nitrogen and phosphorus in aquaculture wastewater.

In this paper, a biological aerated filter (BAF) based on ferromanganese oxide-biochar (FMBC) was constructed to investigated the removal performance and mechanism for conventional pollutants and four kinds of antibiotic, in contrast of conventional zeolite loaded BAF (BAF-A) and bamboo biochar filled BAF (BAF-B). Results showed that the average removal efficiency of total nitrogen (TN), total phosphorus (TP) and antibiotics in a FMBC-BAF (named by BAF-C) were 52.97 ± 2.27%, 51.58 ± 1.92% and 70.36 ± 1.00% ~ 81.65 ± 0.99% respectively in running period (39-100 d), which were significantly higher than those of BAF-A and BAF-B. In the BAF-C, the expression of denitrification enzyme activities and the secretion of extracellular polymeric substance (EPS) especially polyprotein (PN) were effectively stimulated, as well as accelerated electron transfer activity (ETSA) and lower electrochemical impedance spectroscopy (EIS) were acquired. After 100 days of operation, the abundance of nitrogen, phosphorus and antibiotic removal functional bacteria like Sphingorhabdus (4.52%), Bradyrhizobium (1.98%), Hyphomicrobium (2.49%), Ferruginibacter (7.80%), unclassified_f_Blastoca tellaceae (1.84%), norank_f_JG30-KF-CM45 (6.82%), norank_f_norank_o_SBR1031 (2.43%), Nitrospira (2.58%) norank_f_Caldilineaceae (1.53%) and Micropruina (1.11%) were enriched. Mechanism hypothesis of enhanced performances of nutrients and antibiotics removal pointed that: The phosphorus was removed by adsorption and precipitation, antibiotics removal was mainly achieved through the combined action of adsorption and biodegradation, while nitrogen removal was realized by biologic nitrification and denitrification in a FMBC-BAF for aquaculture wastewater treatment.

Exploration of ETV6::ABL1-positive AML with concurrent NPM1 and FLT3-ITD mutations.

ETV6::ABL1 is a rare fusion gene that found in MPN, ALL, and AML. It has a complex and diverse formation mechanism due to the reciprocal orientations of the ETV6 and ABL1 genes relative to the centromeres. NPM1 is frequently mutated in adult AML, often accompanied by FLT3-ITD, which suggests molecular synergisms in AML pathogenesis. Previous reports on ETV6::ABL1 mostly focus on FLT3-ITD. In this study, we present a case of AML with ETV6::ABL1, along with NPM1 and FLT3-ITD. The patient showed a rapid increase in primitive cells at the initial stage, along with the presence of immature granulocytes and erythrocytes. Through cytogenetic analysis, fluorescence in situ hybridization (FISH), and RNA-seq, we elucidated the mechanism behind the formation of the ETV6::ABL1 fusion gene. Despite conventional chemotherapy failure and rapid tumor proliferation, we attempted to add FLT3 inhibitor sorafenib to the treatment, along with chemotherapy bridging to haploidentical transplantation. After haplo-HSCT, a combination of sorafenib and dasatinib was administered as maintenance therapy. The patient achieved complete remission (CR) and maintained it for 11 months. The intricate genetic landscape observed in this case presents diagnostic dilemmas and therapeutic challenges, emphasizing the importance of a comprehensive understanding of its implications for disease classification, risk stratification, and treatment selection.

The effects of diverse microplastics on adzuki bean (Vigna angularis) growth and physiologic properties.

Globally, microplastic pollution of soil ecosystems poses a major risk. The early studies found that the impact of microplastics on different plants could vary depending on the type of microplastic, the mass concentration or the plant species. This study investigated the effect of 3 mass concentrations (0.1%, 1%, and 2.5%) and 3 types of microplastics (PE MPs, PLA MPs, and PVC MPs) on adzuki bean biomass, root traits, Chlorophyll content and antioxidant enzymes. According to our findings, all microplastics had an impact on biomass, but PLA MPs had the strongest inhibitory effect. The high mass concentration of microplastics had a significant influence on chlorophyll content. Adzuki beans exhibited varying degrees of damage upon exposure to microplastics, but they were able to withstand the oxidative stress brought on by PE MPs by increasing the activity of antioxidant enzymes (SOD and POD). Comparing the adverse effects of PE MPs on adzuki beans to those of PLA MPs and PVC MPs, principal component analysis and membership function value analysis revealed that the former had fewer impacts. Disparities in the observed effects may be attributed to variations in the properties of microplastics. Subsequent investigations into the mechanisms underlying microplastic toxicity need a more comprehensive exploration.

New polycyclic polyprenylated acylphloroglucinols with antidepressant activities from Hypericum perforatum L.

Six new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperidiones A-F (1-6), were obtained from Hypericum perforatum L. Their structures were characterized via extensive spectroscopic analyses, the circular dichroism data of the in situ formed [Mo2(OCOCH3)4] complexes, the nuclear magnetic resonance calculation with DP4 + probability analysis, and the calculated electronic circular dichroism (ECD) spectra. Compounds 1-6 are bicyclic polyprenylated acylphloroglucinols with a major bicyclo[3.3.1]nonane-2,4,9-trione skeleton. Notably, compound 1 is a rare PPAP with a hydroperoxy group, and a plausible biosynthetic pathway for 1 was proposed. Compounds 4 and 6 exhibited significant neuroprotective effects under 10 µM against corticosterone (CORT)-injured SH-SY5Y cells. Furthermore, compound 4 demonstrated a noteworthy antidepressant effect at the dose of 5 mg/kg in the tail suspension test (TST) of mice, which was equivalent to 5 mg/kg of fluoxetine. And it potentially exerted an antidepressant effect through the hypothalamic-pituitary-adrenal (HPA) axis.

Weiwei Decoction alleviates gastric intestinal metaplasia through the olfactomedin 4/nucleotide-binding oligomerization domain 1/caudal-type homeobox gene 2 signaling pathway.

BACKGROUND: Gastric intestinal metaplasia (IM) is a precancerous lesion that is associated with an elevated risk of gastric carcinogenesis. Weiwei Decoction (WWD) is a promising traditional Chinese herbal formula widely employed in clinical for treating IM. Previous studies suggested the potential involvement of the olfactomedin 4 (OLFM4)/nucleotide-binding oligomerization domain 1 (NOD1)/caudal-type homeobox gene 2 (CDX2) signaling pathway in IM regulation. AIM: To verify the regulation of the OLFM4/NOD1/CDX2 pathway in IM, specifically investigating WWD's effectiveness on IM through this pathway. METHODS: Immunohistochemistry for OLFM4, NOD1, and CDX2 was conducted on tissue microarray. GES-1 cells treated with chenodeoxycholic acid were utilized as IM cell models. OLFM4 short hairpin RNA (shRNA), NOD1 shRNA, and OLFM4 pcDNA were transfected to clarify the pathway regulatory relationships. Protein interactions were validated by co-immunoprecipitation. To explore WWD's pharmacological actions, IM rat models were induced using N-methyl-N'-nitro-N-nitrosoguanidine followed by WWD gavage. Gastric cells were treated with WWD-medicated serum. Cytokines and chemokines content were assessed by enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction. RESULTS: The OLFM4/NOD1/CDX2 axis was a characteristic of IM. OLFM4 exhibited direct binding and subsequent down-regulation of NOD1, thereby sustaining the activation of CDX2 and promoting the progression of IM. WWD improved gastric mucosal histological lesions while suppressing intestinal markers KLF transcription factor 4, villin 1, and MUCIN 2 expression in IM rats. Regarding pharmacological actions, WWD suppressed OLFM4 and restored NOD1 expression, consequently reducing CDX2 at the mRNA and protein levels in IM rats. Parallel regulatory mechanisms were observed at the protein level in IM cells treated with WWD-medicated serum. Furthermore, WWD-medicated serum treatment strengthened OLFM4 and NOD1 interaction. In case of anti-inflammatory, WWD restrained interleukin (IL)-6, interferon-gamma, IL-17, macrophage chemoattractant protein-1, macrophage inflammatory protein 1 alpha content in IM rat serum. WWD-medicated serum inhibited tumor necrosis factor alpha, IL-6, IL-8 transcriptions in IM cells. CONCLUSION: The OLFM4/NOD1/CDX2 pathway is involved in the regulation of IM. WWD exerts its therapeutic efficacy on IM through the pathway, additionally attenuating the inflammatory response.

Introducing Virtual Shared Medical Appointments as a Novel Treatment Platform for Functional Movement Disorders.

The landscape of medical care has rapidly evolved with technological advancements, particularly through the widespread adoption of virtual appointments catalyzed by the COVID-19 pandemic. This shift has transcended geographical barriers, enhancing access for underserved populations and those with disabilities to specialized healthcare providers. A notable development stemming from this trend is the emergence of virtual shared medical appointments (VSMAs), which integrate group-based education with telemedicine technology. While VSMAs have demonstrated efficacy in conditions such as obesity, diabetes, and neurological disorders, their effectiveness in managing Functional Movement Disorders (FMD) is currently under investigation. FMDs pose unique challenges in diagnosis and acceptance, with high rates of misdiagnosis and treatment delays. VSMAs offer a promising solution by providing educational modules and fostering peer support among patients with similar diagnoses. At the Cleveland Clinic Center for Neurological Restoration, VSMAs have been embraced to enhance care standards for FMD patients. The program facilitates educational sessions and follow-up meetings to improve treatment adherence and psychological well-being. Early outcomes indicate increased patient acceptance and engagement, with significant program growth observed. Ongoing research aims to evaluate stakeholder perspectives and refine session content to further reduce stigma and the healthcare burden associated with FMDs.