Ce-doped TiO2 supported RuO2 as efficient catalysts for the oxidation of HCl to Cl2.

Reducing the cost of RuO2/TiO2 catalysts is still one of the urgent challenges in catalytic HCl oxidation. In the present work, a Ce-doped TiO2 supported RuO2 catalyst with a low Ru loading was developed, showing a high activity in the catalytic oxidation of HCl to Cl2. The results on some extensive characterizations of both Ce-doped TiO2 carriers and their supported RuO2 catalysts show that the doping of Ce into TiO2 can effectively change the lattice parameters of TiO2 to improve the dispersion of the active RuO2 species on the carrier, which facilitates the production of surface Ru species to expose more active sites for boosting the catalytic performance even under some harsh reaction conditions. This work provides some scientific basis and technical support for chlorine recycling.

A real-world pharmacovigilance analysis of eslicarbazepine acetate using the FDA adverse events reporting system (FAERS) database from 2013 (Q4) to 2024 (Q1).

Background: The approval of eslicarbazepine acetate (ESL) by the Food and Drug Administration (FDA) in 2013 marked an advancement in the treatment of adult patients with partial-onset seizures. However, there still remains a paucity of real-world studies regarding the adverse events (AEs) associated with this compound. The principal aim of the present study was to scrutinize ESL-related AEs by leveraging data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: By extracting all available data since the FDA approval of ESL (2013Q4-2024Q1), disproportionality analysis was performed using reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and multi-item gamma Poisson shrinker (MGPS) algorithms. AE signals that simultaneously met the requirements of all four algorithms were identified as significant positive signals. Demographic information, time of onset and gender-specific signal detection were also examined. In addition, a special screening process for designated medical events (DME) was implemented to focus on the evaluation and comparison of safety signals within DME and System Organ Classification (SOC) level, as well as SMQ (Standardised MedDRA Queries) level. Stratified analysis by logistic regression is employed to examine the variations across different gender (male and female) and age groups (<18 years old, 18-64 years old, >65 years old). Results: A total of 5,719 AE reports and 1,907 reported cases were obtained. ESL related AEs were identified in relation to 27 SOCs, among which the significant positive SOCs were nervous system disorders, injury poisoning and procedural complications, etc. There were 86 severely disproportional preferred terms that complied with the four algorithms. Most AEs occurred within the first month after treatment. According to the 86 valuable positive signals with DME screening results, 3 signals of dermatitis exfoliative, stevens-johnson syndrome, drug reaction with eosinophilia and systemic symptoms were consistent with PT signals on the DME-list, with the 3 PTs focusing on skin and subcutaneous tissue disorders and hypersensitivity. Males are more commonly affected by seizures than females. Seizures, hyponatremia, and confusional states were more frequently observed in the elderly population, while aggression, irritability, DRESS (drug reaction with eosinophilia and systemic symptoms), and abnormal behavior were found to be more common in the pediatric population. Both the children and elderly groups exhibited a higher proportion of agitation than the adult group. Conclusion: Our research enhances the safety and tolerability profile of ESL, but the clinical use of ESL should be noticed and avoided in relation to AEs since it raises the risk of dermatitis exfoliative, stevens-johnson syndrome. Particular attention should be paid to DRESS in children and hyponatremia in the elderly.

N6-methyladenosine modification-tuned lipid metabolism controls skin immune homeostasis via regulating neutrophil chemotaxis.

Disrupted N6-methyladenosine (m6A) modification modulates various inflammatory disorders. However, the role of m6A in regulating cutaneous inflammation remains elusive. Here, we reveal that the m6A and its methyltransferase METTL3 are down-regulated in keratinocytes in inflammatory skin diseases. Inducible deletion of Mettl3 in murine keratinocytes results in spontaneous skin inflammation and increases susceptibility to cutaneous inflammation with activation of neutrophil recruitment. Therapeutically, restoration of m6A alleviates the disease phenotypes in mice and suppresses inflammation in human biopsy specimens. We support a model in which m6A modification stabilizes the mRNA of the lipid-metabolizing enzyme ELOVL6 via the m6A reader IGF2BP3, leading to a rewiring of fatty acid metabolism with a reduction in palmitic acid accumulation and, consequently, suppressing neutrophil chemotaxis in cutaneous inflammation. Our findings highlight a previously unrecognized epithelial-intrinsic m6A modification-lipid metabolism pathway that is essential for maintaining epidermal and immune homeostasis and lay the basis for potential therapeutic targeting of m6A modulators to attenuate inflammatory skin diseases.

Genome-wide identification, characterization and expression pattern analysis of TIFY family members in Artemisia argyi.

BACKGROUND: Plant-specific TIFY proteins play crucial roles in regulating plant growth, development, and various stress responses. However, there is no information available about this family in Artemisia argyi, a well-known traditional medicinal plant with great economic value. RESULTS: A total of 34 AaTIFY genes were identified, including 4 TIFY, 22 JAZ, 5 PPD, and 3 ZML genes. Structural, motif scanning, and phylogenetic relationships analysis of these genes revealed that members within the same group or subgroup exhibit similar exon-intron structures and conserved motif compositions. The TIFY genes were unevenly distributed across the 15 chromosomes. Tandem duplication events and segmental duplication events have been identified in the TIFY family in A. argyi. These events have played a crucial role in the gene multiplication and compression of different subfamilies within the TIFY family. Promoter analysis revealed that most AaTIFY genes contain multiple cis-elements associated with stress response, phytohormone signal transduction, and plant growth and development. Expression analysis of roots and leaves using RNA-seq data revealed that certain AaTIFY genes showed tissue-specific expression patterns, and some AaTIFY genes, such as AaTIFY19/29, were found to be involved in regulating salt and saline-alkali stresses. In addition, RT-qPCR analysis showed that TIFY genes, especially AaTIFY19/23/27/29, respond to a variety of hormonal treatments, such as MeJA, ABA, SA, and IAA. This suggested that TIFY genes in A. argyi regulate plant growth and respond to different stresses by following different hormone signaling pathways. CONCLUSION: Taken together, our study conducted a comprehensive identification and analysis of the TIFY gene family in A. argyi. These findings suggested that TIFY might play an important role in plant development and stress responses, which laid a valuable foundation for further understanding the function of TIFY genes in multiple stress responses and phytohormone crosstalk in A. argyi.

Associating plasma aldosterone concentration with the prevalence of MAFLD in hypertensive patients: insights from a large-scale cross-sectional study.

Objective: To explore the link between plasma aldosterone concentration (PAC) and the prevalence of metabolic dysfunction-related fatty liver disease (MAFLD) in hypertensive patients. Methods: We analyzed data from 41,131 hospitalized patients from January 1, 2014, to December 31, 2023. Multivariate logistic regression models tested associations, with threshold, subgroup, and sensitivity analyses conducted to validate findings. Results: For each 5-unit increase in PAC, the risk of MAFLD rose by 1.57 times, consistent even in the fully adjusted model. The odds ratios for the Q2, Q3, and Q4 groups compared to Q1 were 1.21, 2.12, and 3.14, respectively. A threshold effect was observed at 14 ng/dL, with subgroup and sensitivity analyses supporting these results. Conclusions: This study reveals a significant positive association between elevated PAC levels and the prevalence of MAFLD in hypertensive patients. These findings underscore the imperative for further large-scale, prospective studies to validate and expand upon this correlation.

Efficacy and Safety of Roxadustat for Anemia in Patients Receiving Chemotherapy for Nonmyeloid Malignancies: A Randomized, Open-Label, Active-Controlled Phase III Study.

PURPOSE: We evaluated the efficacy and safety of roxadustat, a first-in-class hypoxia-inducible factor prolyl hydroxylase inhibitor, for chemotherapy-induced anemia (CIA) in patients with nonmyeloid malignancies receiving multicycle treatments of chemotherapy. PATIENTS AND METHODS: In this open-label, noninferiority phase III study conducted at 44 sites in China, 159 participants age ≥18 years with CIA nonmyeloid malignancy and CIA were randomly assigned (1:1) to oral roxadustat or subcutaneous recombinant human erythropoietin-α (rHuEPO-α) three times a week for 12 weeks. Roxadustat starting dosages were 100, 120, and 150 mg three times a week for participants weighing 40-<50, 50-60, and >60 kg, respectively. rHuEPO-α starting dosage for all participants was 150 IU/kg three times a week. Both roxadustat and rHuEPO-α dosages could be modified. The primary end point was least-squares mean (LSM) change in hemoglobin (Hb) concentration from baseline to the concentration averaged over weeks 9-13. RESULTS: Of the 159 participants randomly assigned, 140 were included in the per-protocol set (roxadustat, n = 78; rHuEPO-α, n = 62). The LSM (95% two-sided CI) change from baseline to weeks 9-13 in Hb concentration was 17.1 (13.58 to 20.71) g/L with roxadustat and 15.4 (11.34 to 19.50) g/L with rHuEPO-α (mean difference [95% CI], 1.7 [-3.39 to 6.84]). The lower bound of the one-sided 97.5% CI for the treatment difference (‒3.4 g/L) was greater than the predefined noninferiority margin of ‒6.6 g/L, establishing noninferiority. Noninferiority was supported by five of six key secondary end points. Rates of adverse events were generally comparable between treatments and consistent with previous findings. CONCLUSION: Roxadustat was noninferior to rHuEPO-α in treating CIA in participants with nonmyeloid malignancies receiving multicycle treatments of myelosuppressive chemotherapy. The oral formulation of roxadustat may potentially increase compliance.

23-year review of spheno-orbital meningioma: clinical, radiological, and pathological insights from 100 cases.

BACKGROUND: Spheno-orbital meningioma (SOM) represents a unique variant of sphenoid wing meningiomas, distinguished by its propensity for bone infiltration and cranio-orbital involvement. SOM exhibits a considerable incidence of misdiagnosis and recurrence. PURPOSES: To elucidate the clinical, radiological, and pathological characteristics of SOM. METHODS: Review of electronic medical records, histopathology, radiological images and follow-up information of 100 SOM patients. RESULTS: Of the 100 patients (28 males, 72 females) with SOM, mean age was 46.8 ± 12.6 years and prevalent symptoms were proptosis (99%). All the CT scans showed hyperostosis with 89.3% of the hyperostosis having an irregular edge. In MRI scans, dural tail sign was observed across all patients and the cranio-orbital tumors often penetrated temporal muscle (74.1%), extraocular muscle (74.1%) and lacrimal gland (63%). All the 100 patients underwent surgical intervention, and among them, 62 individuals received postoperative radiotherapy. Grade I resections had a lower recurrence rate(16.7%), which further decreased with the addition of radiotherapy(13.9%). In contrast, all patients with grade II or higher grade resections without radiotherapy experienced recurrence, indicating a higher risk associated with less complete tumor removal. The pathological examination revealed that intraorbital sections exhibited comparable tumor density to intraorbital SOM tumors, along with increased fibrous density but decreased vascular distribution. CONCLUSIONS: Radiological characteristics of SOM included cranio-orbital tumors, hyperostosis of the sphenoid wing with an irregular edge, and dural tail sign. Combination of gross total resection and adjuvant radiotherapy was recommended to minimize recurrence rate. Intracranial SOM tumors tended to be softer and more bleed-prone than intraorbital sections, necessitating surgical precision.

Stress Hormones: Unveiling the Role in Accelerated Cellular Senescence.

Cellular senescence is a complex process involving multiple factors, such as genetics, environment, and behavior. However, recent studies have shown that stress also plays a crucial role in inducing cellular senescence. Stress can affect cellular function and structure through various pathways, leading to accelerated aging. Exposure to stressful conditions can alter the neuroendocrine system, activate the hypothalamus-pituitary-adrenal axis and sympathetic adrenal medullary axis, and release cortisol and catecholamines, causing mitochondrial dysfunction, generating excessive reactive oxygen species, and inducing oxidative stress, DNA damage, and inflammatory reactions, ultimately resulting in accelerated cellular senescence. The process of stress-induced cellular senescence has been implicated in a number of chronic diseases, including age-related macular degeneration, chronic kidney disease, type 2 diabetes, cardiovascular disease and obstructive sleep apnea. In this review, we integrate recent progress research progress in our understanding of the mechanisms of stress-induced cellular senescence and discuss its underlying mechanisms from the perspective of stress hormones. We review potential therapeutic targets for stress-induced premature senescence and discuss the advantages and limitations of existing pharmacological agents capable of ameliorating stress-induced premature senescence.

Flexible Temperature Sensor with High Reproducibility and Wireless Closed-Loop System for Decoupled Multimodal Health Monitoring and Personalized Thermoregulation.

Temperature and pulse waves are two fundamental indicators of body health. Specifically, thermoresistive flexible temperature sensors are one of the most applied sensors. However, they suffer from poor reproducibility of resistivity; and decoupling temperature from pressure/strain is still challenging. Besides, autonomous thermoregulation by wearable sensory systems is in high demand, but conventional commercial apparatuses are cumbersome and not suitable for long-term portable use. Here, a material-design strategy is developed to overcome the problem of poor reproducibility of resistivity by tuning the thermal expansion coefficient to nearly zero, precluding the detriment caused by shape expansion/shrinkage with temperature variation and achieving high reproducibility. The strategy also obtains more reliable sensitivity and higher stability, and the designed thermoresistive fiber has strain-insensitive sensing performance and fast response/recovery time. A smart textile woven by the thermoresistive fiber can decouple temperature and pulse without crosstalk; and a flexible wireless closed-loop system comprising the smart textile, a heating textile, a flexible diminutive control patch, and a smartphone is designed and constructed to monitor health status in real-time and autonomously regulate body temperature. This work offers a new route to circumvent temperature-sensitive effects for flexible sensors and new insights for personalized thermoregulation.

Electronegativity- induced cobalt-doped platinum hollow nanospheres with high CO tolerance for efficient methanol oxidation reaction.

Although Platinum (Pt)-based alloys have garnered significant interest within the realm of direct methanol fuel cells (DMFCs), there still exists a notable dearth in the exploration of the catalytic behavior of the liquid fuels on well-defined active sites and unavoidable Pt poisoning because of the adsorbed CO species (COads). Here, we propose an electronegativity-induced electronic redistribution strategy to optimize the adsorption of crucial intermediates for the methanol oxidation reaction (MOR) by introducing the Co element to form the PtCo alloys. The optimal PtCo hollow nanospheres (HNSs) exhibit excellent high-quality activity of 3.27 A mgPt-1, which is 11.6 times and 13.1 times higher than that of Pt/C and pure Pt, respectively. The in-situ Fourier transform infrared reflection spectroscopy validates that electron redistribution could weak CO adsorption, and subsequently decrease the CO poisoning adjacent the Pt active sites. Theoretical simulations result show that the introduction of Co optimize surface electronic structure and reduce the d-band center of Pt, thus optimized the adsorption behavior of COads. This study not only employs a straightforward method for the preparation of Pt-based alloys but also delineates a pathway toward designing advanced active sites for MOR via electronegativity-induced electronic redistribution.

The multifaceted effects of mitochondria in kidney diseases.

Mitochondria serve as the primary site for aerobic respiration within cells, playing a crucial role in maintaining cellular homeostasis. To maintain homeostasis and meet the diverse demands of the cells, mitochondria have evolved intricate systems of quality control, mainly including mitochondrial dynamics, mitochondrial autophagy (mitophagy) and mitochondrial biogenesis. The kidney, characterized by its high energy requirements, is particularly abundant in mitochondria. Interestingly, the mitochondria display complex behaviors and functions. When the kidney is suffered from obstructive, ischemic, hypoxic, oxidative, or metabolic insults, the dysfunctional mitochondrial derived from the defects in the mitochondrial quality control system contribute to cellular inflammation, cellular senescence, and cell death, posing a threat to the kidney. However, in addition to causing injury to the kidney in several cases, mitochondria also exhibit protective effect on the kidney. In recent years, accumulating evidence indicated that mitochondria play a crucial role in adaptive repair following kidney diseases caused by various etiologies. In this article, we comprehensively reviewed the current understanding about the multifaceted effects of mitochondria on kidney diseases and their therapeutic potential.

Comparison of knee biomechanical characteristics during gait between patients with knee osteoarthritis and healthy individuals.

Objective: This study aim to quantify the differences in knee biomechanics during gait between knee osteoarthritis (KOA) patients and healthy individuals. Methods: Twenty KOA patients (4 males and 16 females, 66.2 ± 7.7 years) and twenty controls (16 males and 4 females, 64.8 ± 5.4 years) were recruited for gait test using the motion capture system and force-platform system. The spatiotemporal parameters, knee kinematics and kinetics, and tibiofemoral contact force (TFCF) were calculated using an improved musculoskeletal model. Results: KOA patients walked with reduced speed (48.6 %), stride length (32.9 %), stride height (33.0 %), time proportions of single-support phases (19.2 %), increased gait cycle time (31.0 %), time proportions of stance (8.5 %) and double-support phases (57.7-75.9 %). KOA patients had significant smaller peak flexion angle (29.1 %), flexion ROM (50.6 %) and peak flexion moment (90.2 %), greater peak adduction moment (KAM) (40.7 %), peak rotation moments (KRM) (50.0 %), KAM impulse (106.2 %) and KRM impulse (126.0 %). In proximodistal direction, greater medial TFCF impulse (238 %), total and medial first-peak TFCF (9.6 % and 15.2 %), and smaller lateral peak TFCF (33.3 %) and TFCF impulse (38.4 %) were found in KOA patients. Besides, significant differences were found in the total, medial and lateral peak TFCFs and TFCF impulses in mediolateral direction, and the medial and lateral TFCFs and TFCF impulses in anteroposterior direction. Conclusions: Significant differences were found in the spatiotemporal parameters, knee kinematics and kinetics, and TFCF between the two groups. The results of this study have important implication for clinicians and rehabilitation physicians. These quantified biomechanical differences can provide data support for the personalized and quantified rehabilitation strategies, give suggestions for the exercises of KOA patients, help monitor disease, evaluate surgical treatment, and develop more effective preoperative planning and postoperative rehabilitation strategies.

Few-Human-Interaction Reinforcement Learning for Autonomous Transbronchial Intervention.

The transbronchial interventional surgery presents challenges with winding and convoluted pathways, prone to compression and friction. Current autonomous planning struggles to reach deeper bronchial positions, and hard to consider multiple conflicting goals simultaneously. This article introduces an innovative planning scheme with preference weights to achieve smooth, frictionless, and collision-free autonomous transbronchial intervention with continuum robot (CR). A few-human-interaction twin-delayed deep deterministic policy gradient (FHITD3) generated from surgeon preference guidance is proposed, which determines the optimal strategy for the motion of CR. Preference knowledge is generated through interaction between human and few diversity samples. An abstract actuator space description is proposed for the posture and position representation of CR during movement within bronchus. A contact motion analysis strategy is proposed to calculate real-time attitude of CR in contact with bronchus. In addition, an oscillation suppression approach to address CR's unsmooth distal end trajectory is proposed. Simulated experiments show that the CR autonomously completes intervention tasks with a smooth and stable trajectory, reducing distal end oscillation by over 45%. It achieves a target endpoint within the fourth level bronchus (approximately 5 mm diameter) with over 90% probability.

Identification of genetic association between mitochondrial dysfunction and knee osteoarthritis through integrating multi-omics: a summary data-based Mendelian randomization study.

OBJECTIVE: Association between mitochondrial dysfunction and osteoarthritis (OA) has been consistently investigated, yet their genetic association remains obscure. In this study, mitochondrial-related genes were used as instrumental variables to proxy for mitochondrial dysfunction, and summary data of knee OA (KOA) were used as outcome to examine their genetic association. METHODS: We obtained 1136 mitochondrial-related genes from the human MitoCarta3.0 database. Genetic proxy instruments for mitochondrial-related genes from studies of corresponding gene expression (n = 31,684) and protein (n = 35,559) quantitative trait locus (eQTLs and pQTLs), respectively. Aggregated data for KOA (62,497 KOA cases and 333,557 controls) were extracted from the largest OA genome-wide association study (GWAS). We integrated QTL data with KOA GWAS data to estimate their genetic association using summary data-based Mendelian randomization analysis (SMR). Additionally, we implemented Bayesian colocalization analysis to reveal whether suggestive mitochondrial-related genes and KOA were driven by a same genetic variant. Finally, to validate the primary findings, replication study (24,955 cases and 378,169 controls) and multi-SNP-based SMR (SMR-multi) test was performed. RESULTS: Through SMR analysis, we found that the expression levels of 2 mitochondrial-related genes were associated with KOA risk. Specifically, elevated gene expression levels of the IMMP2L (odds ratio [OR] = 1.056; 95% confidence interval [CI] = 1.030-1.082; P-FDR = 0.004) increased the risk of KOA. Conversely, increased gene expression levels of AKAP10 decreased the risk of KOA (OR = 0.955; 95% CI, 0.934-0.977; P-FDR = 0.019). Colocalization analysis demonstrated that AKAP10 (PP.H4 = 0.84) and IMMP2L (PP.H4 = 0.91) shared the same genetic variant with KOA. In addition, consistent results were found in replication study and SMR-multi test, further demonstrating the reliability of our findings. CONCLUSIONS: In summary, our analyses revealed the genetic association between mitochondrial dysfunction proxied by mitochondrial-related genes and KOA, providing new insight into potential pathogenesis of KOA. Furthermore, these identified candidate genes offer the possibility of clinical drug target development for KOA. Key points • This is the first SMR study to explore the genetic association between mitochondrial dysfunction proxied by mitochondrial-related genes and KOA. • Sufficient evidence to support genetic association between the expression levels of AKAP10 and IMMP2L, and KOA • Our MR analysis may provide novel new insight into potential pathogenesis of KOA. • These identified candidate genes offer the possibility of clinical drug target development for KOA.

Three-Dimensional Geometry Values and Clinical Determinants for the Annulus of the Tricuspid Valve in a Japanese Population.

The tricuspid annulus (TA) is the primary target of tricuspid valve (TV) surgery for tricuspid regurgitation (TR). However, the reference values for TA geometry in the Japanese population is currently unavailable. We aimed to elucidate the geometric reference values of the TA in Japanese individuals using 3-dimensional (3D) echocardiography.We conducted a prospective study using transthoracic 3D echocardiography on 142 healthy Japanese subjects aged between 20 and 79 years. The tricuspid geometric parameters in the late-diastole and the mid-systole were analyzed using custom 3D software (Realview™).After excluding 46 subjects with poor images, data from 96 subjects (67.6%) were analyzed. TA area and circumference showed strong correlations with body surface area (BSA) (P < 0.001 for all), while some of these parameters exhibited weak correlations with age. Gender differences in TV geometry were assessed across 3 age groups: 20-39 years (42 subjects), 40-59 years (28 subjects), and 60-79 years (26 subjects). In the youngest subjects (20-39 years), males had a significantly larger TA area and smaller anterior-posterior and medial-lateral diameters (P < 0.001 for all), even after adjusting for BSA, indicating gender differences of TA geometry. These differences diminished with age.We present reference values for TA geometry by age and gender in a Japanese cohort. BSA may be a suitable metric for indexing the TA parameters. While age-related changes in TA parameters may not be significant, gender differences, particularly in younger individuals, persist even after adjusting for BSA.

Integration of induction, system optimization and genetic transformation in Veratrum californicum var. vitro cultures to enhance the production of cyclopamine and veratramine.

Cyclopamine, a compound found in wild Veratrum has shown promising potential as a lead anti-cancer drug by effectively blocking cancer signaling pathways. However, its complex chemical structure poses challenges for artificial synthesis, thus limiting its supply and downstream drug production. This study comprehensively utilizes induction, system optimization, and transgenic technologies to establish an efficient suspension culture system for the high-yield production of cyclopamine and its precursor, veratramine. Experimental results demonstrate that methyl jasmonate (MeJA) effectively promotes the content of veratramine and cyclopamine in Veratrum californicum var. callus tissue, while yeast extract (YE) addition significantly increases cell biomass. The total content of veratramine and cyclopamine reached 0.0638 mg after synergistic treatment of suspension system with these two elicitors. And the content of the two substances was further increased to 0.0827 mg after the optimization by response surface methodology. Subsequently, a genetic transformation system for V. californicum callus was established and a crucial enzyme gene VnOSC1, involved in the steroidal alkaloid biosynthesis pathway, was screened and identified for genetic transformation. Combined suspension culture and synergistic induction system, the total content of the two substances in transgenic suspension system was further increased to 0.1228 mg, representing a 276.69% improvement compared to the initial culture system. This study proposes a complete and effective genetic transformation and cultivation scheme for V. californicum tissue cells, achieving milligram-level production of the anticancer agent cyclopamine and its direct precursor veratramine for the first time. It provides a theoretical basis for the industrial-scale production of these substances.

METTL16 Promotes Stability of SYNPO2L mRNA and leading to Cancer Cell Lung Metastasis by Secretion of COL10A1 and attract the Cancer-Associated Fibroblasts.

The occurrence of metastasis is a major factor contributing to poor prognosis in colorectal cancer. Different stages of the disease play a crucial role in distant metastasis. Furthermore, m6A has been demonstrated to play a significant role in regulating tumor metastasis. Therefore, we conducted an analysis of transcriptome data from high-stage and low-stage colorectal cancer patients in The Cancer Genome Atlas (TCGA) to identify genes associated with m6A-related regulation. We identified SYNPO2L as a core gene regulated by m6A, and it is correlated with adverse prognosis and metastasis in patients. Additionally, we demonstrated that the m6A writer gene Mettl16 can regulate the stability of SYNPO2L through interaction with YTHDC1. Subsequently, using Weighted Gene Co-expression Network Analysis (WGCNA), we discovered that SYNPO2L can regulate COL10A1, mediating the actions of Cancer-Associated Fibroblasts. SYNPO2L promotes the secretion of COL10A1 and the infiltration of tumor-associated fibroblasts, thereby facilitating Epithelial-Mesenchymal Transition (EMT) in tumor cells and making them more prone to distant metastasis.

p75ECD-Fc reverses neonatal hypoxic-ischemic encephalopathy-induced neurological deficits and inhibits apoptosis associated with Nestin.

A recent study has introduced a recombinant fusion protein, consisting of the extracellular domain (ECD) of p75 and the Fc fragment of human immunoglobulin IgG1 (p75ECD-Fc), as a multifaceted agent within the nervous system. This research aimed to assess the effects of p75ECD-Fc on neuronal growth and the restoration of neurological functions in rats afflicted with neonatal hypoxic-ischemic encephalopathy (NHIE). In vitro analyses revealed that 1 µM p75ECD-Fc treatment markedly increased cell viability and facilitated neurite outgrowth in neurons exposed to oxygen-glucose deprivation (OGD). Subsequent in vivo studies determined that a dose of 78.6 µg/3 µl of p75ECD-Fc significantly mitigated brain damage and both acute and long-term neurological impairments, outperforming the therapeutic efficacy of hypothermia, as evidenced through behavioral assessments. Additionally, in vivo immunostaining showed that p75ECD-Fc administration enhanced neuronal survival and regeneration, and reduced astrocytosis and microglia activation in the cortex and hippocampus of NHIE rats. A noteworthy shift from A1 to A2 astrocyte phenotypes and from M1 to M2 microglia phenotypes was observed after p75ECD-Fc treatment. Furthermore, a co-expression of the p75 neurotrophin receptor (p75NTR) and Nestin was identified, with an overexpression of Nestin alleviating the neurological dysfunction induced by NHIE. Mechanistically, the neuroprotective effects of p75ECD-Fc, particularly its inhibition of neuronal apoptosis post-OGD, may be attributed to Nestin. Taken together, these results highlight the neuroprotective and anti-inflammatory effects of p75ECD-Fc treatment through the modulation of glial cell phenotypes and the Nestin-mediated inhibition of neuronal apoptosis, positioning it as a viable therapeutic approach for NHIE.

Shugan Jieyu capsule effects on peripheral blood micro-124, micro-132, and brain-derived neurotrophic factor in patients with mild to moderate depression.

BACKGROUND: To assess the effectiveness of Shugan Jieyu capsules on peripheral blood miR-124, miR-132, and brain-derived neurotrophic factor (BDNF) levels in patients with mild to moderate depression following coronary artery intervention [percutaneous coronary intervention (PCI)] for coronary heart disease. AIM: To evaluate the therapeutic efficacy of Shugan Jieyu capsules and their effects on the peripheral blood levels of miR-124, miR-132, and BDNF in patients with mild to moderate depression following PCI for coronary heart disease. METHODS: Patients with mild-to-moderate depression of the liver-qi stagnation type after PCI for coronary heart disease at the 305th Hospital of the People's Liberation Army were enrolled from June 2022 to November 2023 and randomly assigned to two groups: Experimental (treated with Shugan Jieyu capsules) and control (treated with escitalopram oxalate tablets). This study compared the antidepressant effects of these treatments using 17-item Hamilton Rating Scale for Depression (HAMD-17) scores, metabolic equivalents, low-density lipoprotein cholesterol, BDNF, high-sensitivity C-reactive protein levels, miR-124 and miR-132 levels, distribution of immune-related lymphocyte subsets, and traditional Chinese medicine syndrome scores before and after 6 weeks of treatment. RESULTS: No significant difference was observed in any index between the two groups before treatment (P > 0.05). After treatment, the total efficacy rates were 93.33% and 90.00% in the experimental and control groups, respectively. Experimental group had significantly lower scores for the main and secondary syndromes compared to the control group (P < 0.05). No significant difference was observed in the metabolic equivalents between the two groups before and after treatment (P > 0.05). The levels of low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and miR-132 were significantly lower, whereas those of miR-124, BDNF, CD3+T lymphocytes, CD3+CD4+T helper lymphocytes, and CD3+CD4+/CD3+CD8+ cells were significantly higher in the experimental group compared to the control group (P < 0.05). The incidence of adverse reactions during experimental group was significantly lower than that in control group (P < 0.05). CONCLUSION: Shugan Jieyu capsules have good efficacy in patients with mild-to-moderate depression after PCI, and its mechanism may contribute to the regulation of miR-124, miR-132, BDNF levels, and lymphoid immune cells.