Global richness patterns of alpine genus Gentiana depend on multiple factors.

Environmental factors impact species richness differently across taxonomic groups, and understanding the geographic patterns and drivers influencing alpine plant richness remains limited. This study compiled global distribution data of 404 species of Gentiana, an alpine genus, and analyzed the relative effects of different environmental factors and several previously proposed models on the variation of Gentiana richness. By evaluating the effects of range size and regions on the relationships between Gentiana richness and environmental factors, we found that all tested environmental factors had weak effects on richness variation for all species and wide-ranging species, while habitat heterogeneity was the best predictor for narrow-ranging species. Habitat heterogeneity was the main driver of richness variation in Europe and Asia, but not in North America. The multiple regression model that included variables for energy, water, seasonality, habitat heterogeneity and past climate change had the highest explanatory power, but it still explained less than 50% of the variation in species richness for all Gentiana species at both global and regional scale, except for Europe. The limited explanatory power of environmental factors in explaining species richness patterns for all species, along with the variations observed among regions, suggest that other factors, such as evolutionary processes and biogeographic history may have also influenced the geographic patterns of Gentiana species richness. In conclusion, our results indicate a limited influence of climate factors on alpine species richness, while habitat heterogeneity, along with its impacts on speciation and dispersal, likely play significant roles in shaping the richness of alpine Gentiana species.

The influence of water safety knowledge on adolescents' drowning risk behaviors: a framework of risk-protect integrated and KAP theory.

Introduction: Although previous research has examined the risk factors for drowning behavior among adolescents, it is unclear whether this association is influenced by water safety knowledge. This study aimed to examine whether water safety knowledge is associated with adolescents' drowning risk behaviors and whether drowning risk perceptions and attitudes could have a chain mediating role in the association between water safety knowledge and adolescents' drowning risk behaviors. Methods: This study included 7,485 adolescents from five Chinese provinces and cities. We used the Drowning Risk Behaviors Scales (DRBS) to evaluate the risk of drowning behaviors. The Water Safety Knowledge Scale (WSKS) was used to evaluate the competence level of water safety knowledge. The Drowning Risk Perceptions Scale (DRPS) was used to evaluate the risk level of perceptions, and the Drowning Risk Attitudes Scale (DRAS) was used to evaluate the risk level of attitudes. Results: The results of the mediating effect test showed that water safety knowledge (WSK) affected drowning risk behaviors (DRB) through three indirect paths. Drowning risk perceptions (DRP) and attitudes (DRA) have significantly mediated the association between WSK and DRB. In conclusion, DRP and DRA can act as mediators between WSK and DRB, not only individually, but also as chain mediators, where the direct effect is-0.301, the total indirect effect is-0.214, and the total mediated indirect effect is 41.5%. Discussion: Water safety knowledge negatively predicts adolescents' drowning risk behaviors; water safety knowledge has an inhibitory effect on drowning risk perceptions. Water safety knowledge can directly influence adolescents' drowning risk perceptions and indirectly affect drowning risk behaviors through the mediation of drowning risk perceptions and attitudes comprising three paths: (1) the drowning risk perceptions mediation path, (2) the drowning risk attitudes mediation path, and (3) the drowning risk perceptions and attitudes mediation paths.

Saponin monomers: Potential candidates for the treatment of type 2 diabetes mellitus and its complications.

Type 2 diabetes mellitus (T2DM), a metabolic disease with persistent hyperglycemia primarily caused by insulin resistance (IR), has become one of the most serious health challenges of the 21st century, with considerable economic and societal implications worldwide. Considering the inevitable side effects of conventional antidiabetic drugs, natural ingredients exhibit promising therapeutic efficacy and can serve as safer and more cost-effective alternatives for the management of T2DM. Saponins are a structurally diverse class of amphiphilic compounds widely distributed in many popular herbal medicinal plants, some animals, and marine organisms. There are many saponin monomers, such as ginsenoside compound K, ginsenoside Rb1, ginsenoside Rg1, astragaloside IV, glycyrrhizin, and diosgenin, showing great efficacy in the treatment of T2DM and its complications in vivo and in vitro. However, although the mechanisms of action of saponin monomers at the animal and cell levels have been gradually elucidated, there is a lack of clinical data, which hinders the development of saponin-based antidiabetic drugs. Herein, the main factors/pathways associated with T2DM and the comprehensive underlying mechanisms and potential applications of these saponin monomers in the management of T2DM and its complications are reviewed and discussed, aiming to provide fundamental data for future high-quality clinical studies and trials.

Clarification of the infection pattern of Xanthomonas citri subsp. citri on citrus fruit by artificial inoculation.

BACKGROUND: Citrus canker is a significant bacterial disease caused by Xanthomonas citri subsp. citri (Xcc) that severely impedes the healthy development of the citrus industry. Especially when citrus fruit is infected by Xcc, it will reduce or even lost its commercial value. However, due to the prolonged fruiting cycle and intricate structure, much less research progress had been made in canker disease on fruit than on leaf. In fact, limited understanding has been achieved on canker development and the response to Xcc infection in fruit. RESULTS: Herein, the progression of canker disease on sweet orange fruit was tracked in the field. Results indicated that typical lesions initially appear on the sepal, style residue, nectary disk, epicarp, and peduncle of young fruits after petal fall. The susceptibility of fruits to Xcc infection diminished as the fruit developed, with no new lesions forming at the ripening stage. The establishment of an efficient method for inoculating Xcc on fruit as well as the artificial inoculation throughout the fruit's developmental cycle clarified this infection pattern. Additionally, microscopic observations during the infection process revealed that Xcc invasion caused structural changes on the surface and cross-section of the fruit. CONCLUSIONS: An efficient system for inoculation on citrus fruit with Xcc was established, by which it can serve for the evaluation of citrus germplasm for canker disease resistance and systematic research on the interactions between Xcc and citrus fruits.

Update on diabetic retinopathy during pregnancy.

Diabetes mellitus (DM) leads to several vascular and neurological complications, including diabetic retinopathy (DR). As the population ages, health problems in certain groups, including children and pregnant women, are drawing more and more attention. Pregnancy is one of the independent risk factors for the development and progression of DR. Pregnancy-induced changes may contribute to or worsen DR, which can cause a tremendous burden on public health. It is essential for pregnant women with DR and their offspring to minimize the risk of vision loss from DR in this population and adverse outcomes by understanding the development and processes behind this process. Thus, we have updated the recent situation of epidemiology, evolution characteristics, risk factors, pathophysiology, pregnancy outcomes for a better understanding of the latest status of DR, helping to improve maternal and neonatal pregnancy outcomes, and promoting health for women with DR.

Photodynamic effect of vascular-targeted polyphenol nanoparticles on Endothelial cells.

BACKGROUND: Port wine stains (PWS) are vascular malformations, and photodynamic therapy (PDT) is a promising treatment. Emerging drug delivery methods employ nanoparticles (NPs) to enhance drug permeability and retention in diseased blood vessels and improve drug bioavailability. (-) -epigallocatechin-3-gallate glycine (EGCG) has anti-angiogenetic effects and boosts photodynamic therapy. Chlorin e6 (Ce6) is capable of efficiently producing singlet oxygen, rendering it a very promising photosensitizer for utilization in nanomedicine. MATERIAL AND METHODS: EGCG-Ce6-NPs were synthesized and characterized using various techniques. The photodynamic effects of EGCG-Ce6-NPs on endothelial cells were evaluated. The compatibility and toxicity of the nanoparticle was tested using the CCK-8 assay. The intracellular uptake of the nanoparticle was observed using an inverted fluorescence microscope, and the intracellular fluorescence intensity was detected using flow cytometry. The ROS generation and apoptosis induced by EGCG-Ce6-NPs was observed using confocal laser scanning microscopy and flow cytometry respectively. RESULTS: EGCG-Ce6-NPs exhibited stability, spherical shape of uniform size while reducing the particle diameter, low polydisperse profile and retaining the ability to effectively generate singlet oxygen. These characteristics suggest promising potential for enhancing drug permeability and retention. Additionally, EGCG-Ce6-NPs demonstrated good compatibility with endothelial cells and enhanced intracellular uptake of Ce6. Furthermore, EGCG-Ce6-NPs increased activation efficiency, induced significant toxicity, more reactive oxygen species, and a higher rate of late apoptosis after laser irradiation. CONCLUSION: This in vitro study showed the potentials EGCG-Ce6-NPs for the destruction of endothelial cells in vasculature.

Adaptive laboratory evolution of Clostridium autoethanogenum to metabolize CO2 and H2 enhances growth rates in chemostat and unravels proteome and metabolome alterations.

Gas fermentation of CO2 and H2 is an attractive means to sustainably produce fuels and chemicals. Clostridium autoethanogenum is a model organism for industrial CO to ethanol and presents an opportunity for CO2-to-ethanol processes. As we have previously characterized its CO2/H2 chemostat growth, here we use adaptive laboratory evolution (ALE) with the aim of improving growth with CO2/H2. Seven ALE lineages were generated, all with improved specific growth rates. ALE conducted in the presence of 2% CO along with CO2/H2 generated Evolved lineage D, which showed the highest ethanol titres amongst all the ALE lineages during the fermentation of CO2/H2. Chemostat comparison against the parental strain shows no change in acetate or ethanol production, while Evolved D could achieve a higher maximum dilution rate. Multi-omics analyses at steady state revealed that Evolved D has widespread proteome and intracellular metabolome changes. However, the uptake and production rates and titres remain unaltered until investigating their maximum dilution rate. Yet, we provide numerous insights into CO2/H2 metabolism via these multi-omics data and link these results to mutations, suggesting novel targets for metabolic engineering in this bacterium.

Real-world crash configurations and traffic violations among newly licensed young drivers with different route familiarity levels.

OBJECTIVE: Young drivers aged 24 and below are at heightened risks of being influenced by their route familiarity levels. This study aims to compare prevalences of crash culpability, crash configurations and risky driver behaviors among newly licensed young drivers when they are driving on roads with different route familiarity levels. METHODS: Based on the road traffic crash and violation data in Yunnan Province of China from January 2017 through December 2019, we classified drivers' different route familiarity levels by utilizing spatial distance away from residence-based method, including driving on high route familiarity (HRF) and low route familiarity (LRF) roads. Prevalence ratios were estimated using generalized estimating equation log-binomial regression models. RESULTS: We identified 12016 newly licensed young drivers driving on HRF roads and 2189 drivers on LRF roads. Within 48 months of licensure, young drivers on LRF roads were more likely to be at fault for their motor vehicle crashes than those on HRF roads. Young drivers on LRF roads were more likely to be with failure to obey traffic control device, with failure to yield right of way, wrong way driving, backing unsafely and improper parking compared with those on HRF roads. Drivers on LRF roads were less likely to be inattentive and driving with unsafe speed and following too closely compared with those on HRF roads. CONCLUSIONS: Several basic aspects of targeted countermeasures can be put forward. Visual impacts such as rectangular rapid-flashing beacon (RRFB) can be used in order to prevent wrong way driving on the tourist roadways. Arranging safety talks and programs in colleges and universities and technical interventions like Advanced Driver Assistance Systems (ADAS) can be used to reduce young drivers' driving distraction and overconfidence. It is recommended that the driving schools can use these research findings to include in licensure program to make young drivers more aware of the various factors that expose them to crash risks so that more defensive driving may be needed under different situations, and this can also help build the graduated driving licensure (GDL) programme in China.

Integrative Analysis of Transcriptome and Metabolome Sheds Light on Flavonoid Biosynthesis in the Fruiting Body of Stropharia rugosoannulata.

Flavonoids are a diverse family of natural compounds that are widely distributed in plants and play a critical role in plant growth, development, and stress adaptation. In recent years, the biosynthesis of flavonoids in plants has been well-researched, with the successive discovery of key genes driving this process. However, the regulation of flavonoid biosynthesis in fungi remains unclear. Stropharia rugosoannulata is an edible mushroom known for its high nutritional and pharmacological value, with flavonoids being one of its main active components. To investigate the flavonoid content of S. rugosoannulata, a study was conducted to extract and determine the total flavonoids at four stages: young mushroom (Ym), gill (Gi), maturation (Ma), and parachute-opening (Po). The findings revealed a gradual increase in total flavonoid concentration as the fruiting body developed, with significant variations observed between the Ym, Gi, and Ma stages. Subsequently, we used UPLC-MS/MS and transcriptome sequencing (RNA-seq) to quantify the flavonoids and identify regulatory genes of Ym, Gi, and Ma. In total, 53 flavonoid-related metabolites and 6726 differentially expressed genes (DEGs) were identified. Through KEGG pathway enrichment analysis, we identified 59 structural genes encoding flavonoid biosynthesis-related enzymes, most of which were up-regulated during the development of the fruiting body, consistent with the accumulation of flavonoids. This research led to the establishment of a comprehensive transcriptional metabolic regulatory network encompassing flavonoids, flavonoid synthases, and transcription factors (TFs). This represents the first systematic exploration of the molecular mechanism of flavonoids in the fruiting of fungi, offering a foundation for further research on flavonoid mechanisms and the breeding of high-quality S. rugosoannulata.

Efficacy of electro-acupuncture versus sham acupuncture for diabetic peripheral neuropathy: study protocol for a three-armed randomised controlled trial.

INTRODUCTION: Specific treatment for diabetic peripheral neuropathy (DPN) is still lacking, and acupuncture may relieve the symptoms. We intend to investigate the efficacy and safety of electro-acupuncture (EA) in alleviating symptoms associated with DPN in diabetes. METHODS AND ANALYSIS: This multicentre, three-armed, participant- and assessor-blind, randomised, sham-controlled trial will recruit 240 eligible participants from four hospitals in China and will randomly assign (1:1:1) them to EA, sham acupuncture (SA) or usual care (UC) group. Participants in the EA and SA groups willl receive either 24-session EA or SA treatment over 8 weeks, followed by an 8-week follow-up period, while participants in the UC group will be followed up for 16 weeks. The primary outcome of this trial is the change in DPN symptoms from baseline to week 8, as rated by using the Total Symptom Score. The scale assesses four symptoms: pain, burning, paraesthesia and numbness, by evaluating the frequency and severity of each. All results will be analysed with the intention-to-treat population. ETHICS AND DISSEMINATION: The protocol has been approved by the Ethics Committee of the Beijing University of Chinese Medicine (Identifier: 2022BZYLL0509). Every participant will be informed of detailed information about the study before signing informed consent. The results of this trial will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2200061408.

Primary cardiac angiosarcoma: Imaging characterization.

This case report describes a 35-year-old female patient who presented with palpitations and shortness of breath. Imaging findings suggested a cardiac tumor, histopathology confirmed primary cardiac angiosarcoma. This tumor is highly aggressive, usually occurs in the right atrium, lacks specificity in clinical presentation, is prone to early metastasis, and has a poor prognosis. Echocardiography is the method of choice for early detection and is important in assessing tumor size, location, mode of attachment and whether cardiac function is impaired.

High paternal homocysteine causes ventricular septal defects in mouse offspring.

Maternal hyperhomocysteinemia is widely considered as an independent risk of congenital heart disease (CHD). However, whether high paternal homocysteine causes CHD remains unknown. Here, we showed that increased homocysteine levels of male mice caused decreased sperm count, sperm motility defect and ventricular septal defect of the offspring. Moreover, high levels of paternal homocysteine decrease sperm DNMT3A/3B, accompanied with changes in DNA methylation levels in the promoter regions of CHD-related genes. Folic acid supplement could decrease the occurrence of VSD in high homocysteine male mice. This study reveals that increased paternal homocysteine level increases VSD risk in the offspring, indicating that decreasing paternal homocysteine may be an intervening target of CHD.

A case report of pediatric biliary botryoid rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children, and botryoid rhabdomyosarcoma (BRMS) represents a subtype of RMS. BRMS primarily occurs in infants, young children, and adolescent females, with a predilection for mucosa-lined hollow organs such as the bladder, vagina, bile duct, and so on. Its occurrence in the biliary tract is extremely rare. Due to the high malignancy and rapid metastasis of biliary botryoid rhabdomyosarcoma, early diagnosis and treatment are crucial for improving prognosis.

Tolerogenic dendritic cells alleviate collagen-induced arthritis by regulating T-cell differentiation and inhibiting NLRP3-mediated apoptosis.

OBJECTIVE: Tolerogenic dendritic cells (tolDCs) have emerged as a potential treatment for rheumatoid arthritis (RA). However, the detailed mechanism requires further investigation. In this study, we aimed to explore the effects of tolDCs on T-cell differentiation and NLRP3-mediated pyroptosis in a collagen-induced arthritis (CIA) rat model. METHODS: TolDCs were induced using NF-κB ODN decoy. The efficacy of tolDCs intervention in alleviating arthritis symptoms was evaluated in CIA rats. Flow cytometry was employed to analyze CD4+ T-cell subpopulations, while scanning electron microscopy was utilized to observe pyroptosis morphology. Immunohistochemistry was used to assess the expression of pyroptosis-associated proteins. RESULTS: TolDCs intervention significantly reduced joint inflammation and damage in CIA rats. Moreover, it successfully restored the balance of Th1/Th2 cells as well as the balance of Treg/Th17 cells. Furthermore, tolDCs intervention effectively suppressed NLRP3-mediated pyroptosis in the synovium, decreasing the release of IL-1ß and IL-18. CONCLUSION: Our findings underscore the efficacy of tolDCs in attenuating CIA progression through modulation of CD4+ T-cell subpopulations and inhibition of NLRP3-mediated pyroptosis.

Effect of continuous renal replacement therapy on the clinical efficacy and pharmacokinetics of polymyxin B in the treatment of severe pulmonary infection.

Objective: This study aimed to evaluate the pharmacokinetics of polymyxin B in patients with ventilator-associated pneumonia caused by multi-drug resistant bacteria, and to analyze the effect of continuous renal replacement therapy (CRRT) on pharmacokinetics of polymyxin B. Methods: Thirty-five patients with ventilator-associated pneumonia caused by multi-drug resistant bacteria admitted to our hospital from June 2021 to January 2022 were selected as the subjects. The patients were divided into the standard group (n = 20) and the non-standard group (n = 15) based on the factors affecting the compliance of polymyxin B plasma concentration. The patients received with polymyxin B and the plasma concentration was monitored. According to the monitoring results, they were divided into the standard group and the non-standard group, to analyze the influencing factors of polymyxin B on the blood concentration. Besides, the patients were then divided into the control group (n = 28) and the observation group (n = 7) according to whether the patients received CRRT treatment. Patients in the control group treated with polymyxin B alone, while patients in the observation group received with polymyxin B and CRRT. The general data of patients in the two groups were compared. The levels of plasma concentration of polymyxin B measured before the next administration (Cmin), peak plasma concentration of polymyxin B measured immediately after end of infusion (Cmax) and intermediate plasma concentration measured 6 h after administration (midpoint of the dosing interval) (C1/2t) were detected and compared between the two groups. Correlation between pharmacokinetics and efficacy was analyzed by Spearman correlation. The incidence of complications and the 28-day mortality rate of the two groups were recorded. Results: The age, body mass index (BMI) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores in the non-standard group were higher than these in the standard group (p < 0.05). BMI and APACHE II scores were independent risk factors affecting the pharmacokinetics of polymyxin B in patients with severe pulmonary infection (p < 0.05). There were no significant differences in age, BMI, APACHEII score, alanine aminotransferase level, aspartate aminotransferase level, albumin level, gender and diabetes ratio between the control group and the observation group (p > 0.05). The levels of Cmin, Cmax, and C1/2t in the observation group were lower than these in the control group (p < 0.001). The response rate was 50.00% in the control group and 36.36% in the observation group (p > 0.05). The levels of Cmin, Cmax, and C1/2t in the observation group were no significant correlation with the clinical efficacy (p > 0.05), while these in the control group were positive correlation with the clinical efficacy (r = 0.485, p < 0.05). There was no significant difference in the incidence of skin pigmentation, nephrotoxicity and 28-day mortality between the two groups (p > 0.05). Conclusion: In patients with ventilator-associated pneumonia not receiving multidrug-resistant bacteria, the rate of achieving blood drug concentration with the usual recommended dose of polymyxin B was satisfactory. However, the proportion of patients with a 6-h plasma concentration exceeding the maximum plasma concentration was high. BMI and APACHE II scores were important factors affecting the pharmacokinetics of polymyxin B. In patients undergoing CRRT, the plasma concentration of polymyxin B was significantly reduced, suggesting that in patients with severe disease, plasma concentration monitoring played an important role in drug efficacy and patient safety. In patients treated with CRRT, the dose of polymyxin B may need to be increased.

Deoxynivalenol Damages Corneal Epithelial Cells and Exacerbates Inflammatory Response in Fungal Keratitis.

BACKGROUND: Fungal keratitis (FK) is a kind of infectious keratopathy with a high rate of blindness worldwide. Deoxynivalenol (DON) has been proven to have multiple toxic effects on humans and animals. OBJECTIVES: The aim of this study was to explore a possible pathogenic role of DON in FK. METHODS: We first made an animal model of FK in New Zealand white rabbits, and then attempted to detect DON in a culture medium in which Fusarium solani had been grown and also in the corneal tissue of the animal model of Fusarium solani keratitis. Next, a model of DON damage in human corneal epithelial cells (HCECs) was constructed to evaluate effects of DON on the activity, migration ability, cell cycle, and apoptosis in the HCECs. Then, putative the toxic damaging effects of DON on rabbit corneal epithelial cells and the impact of the repair cycle were studied. The expression levels of inflammatory factors in the corneas of the animal model and in the model of DON-damaged HCECs were measured. RESULTS: The Fusarium solani strain used in this study appeared to have the potential to produce DON, since DON was detected in the corneal tissue of rabbits which had been inoculated with this Fusarium solani strain. DON was found to alter the morphology of HCECs, to reduce the activity and to inhibit the proliferation and migration of HCECs. DON also induced the apoptosis and S-phase arrest of HCECs. In addition, DON was found to damage rabbit corneal epithelial cells, to prolong the corneal epithelial regeneration cycle, and to be associated with the upregulated expression of inflammatory factors in HCECs and rabbit corneas. CONCLUSIONS: DON appears to have a toxic damaging effect on HCECs in FK, and to induce the expression of inflammatory factors, leading to the exacerbation of keratitis and the formation of new blood vessels. Future studies will explore the possibility of developing a test to detect DON in ophthalmic settings to aid the rapid diagnosis of FK, and to develop DON neutralizers and adsorbents which have the potential to improve keratocyte status, inhibit apoptosis, and alleviate inflammation, therein providing new thinking for therapy of clinical FK.

Limb Fractures Treated With the Novel Plate Osteosynthesis Application Technique: Second to Minimally Invasive Plates osteosynthesis.

BACKGROUND: The main aim of this article was to propose a new concept of minimally invasive surgery for treating limb fractures, named as second to minimally invasive plates osteosynthesis (STMIPO). METHODS: We have described the STMIPO technique in a step-wise and standardized manner based on our findings from a study involving six patients treated at our institution. All patients with fracture achieved satisfactory outcomes. RESULTS: Ours clinical trials have shown that the STMIPO technique can be successfully applied in various limb fractures, including fibula fractures, tibial fractures, femur fractures, humerus fractures, ulna fractures, and radius fractures. All fracture patients achieved satisfactory outcomes. CONCLUSION: As a new minimally invasive technology, the STMIPO technique can serve as an alternative solution for fractures that are difficult to reduce with minimally invasive plates osteosynthesis (MIPO).

Spinal Nmur2-positive Neurons Play a Crucial Role in Mechanical Itch.

The dorsal spinal cord is crucial for the transmission and modulation of multiple somatosensory modalities, such as itch, pain, and touch. Despite being essential for the well-being and survival of an individual, itch and pain, in their chronic forms, have increasingly been recognized as clinical problems. Although considerable progress has been made in our understanding of the neurochemical processing of nociceptive and chemical itch sensations, the neural substrate that is crucial for mechanical itch processing is still unclear. Here, using genetic and functional manipulation, we identified a population of spinal neurons expressing neuromedin U receptor 2 (Nmur2+) as critical elements for mechanical itch. We found that spinal Nmur2+ neurons are predominantly excitatory neurons, and are enriched in the superficial laminae of the dorsal horn. Pharmacogenetic activation of cervical spinal Nmur2+ neurons evoked scratching behavior. Conversely, the ablation of these neurons using a caspase-3-based method decreased von Frey filament-induced scratching behavior without affecting responses to other somatosensory modalities. Similarly, suppressing the excitability of cervical spinal Nmur2+ neurons via the overexpression of functional Kir2.1 potassium channels reduced scratching in response to innocuous mechanical stimuli, but not to pruritogen application. At the lumbar level, pharmacogenetic activation of these neurons evoked licking and lifting behaviors. However, ablating these neurons did not affect the behavior associated with acute pain. Thus, these results revealed the crucial role of spinal Nmur2+ neurons in mechanical itch. Our study provides important insights into the neural basis of mechanical itch, paving the way for developing novel therapies for chronic itch. PERSPECTIVE: Excitatory Nmur2+ neurons in the superficial dorsal spinal cord are essential for mechanical but not chemical itch information processing. These spinal Nmur2+ neurons represent a potential cellular target for future therapeutic interventions against chronic itch. Spinal and supraspinal Nmur2+ neurons may play different roles in pain signal processing.

Ferroptosis: a potential target for the treatment of atherosclerosis.

Atherosclerosis (AS), the main contributor to acute cardiovascular events, such as myocardial infarction and ischemic stroke, is characterized by necrotic core formation and plaque instability induced by cell death. The mechanisms of cell death in AS have recently been identified and elucidated. Ferroptosis, a novel iron-dependent form of cell death, has been proven to participate in atherosclerotic progression by increasing endothelial reactive oxygen species (ROS) levels and lipid peroxidation. Furthermore, accumulated intracellular iron activates various signaling pathways or risk factors for AS, such as abnormal lipid metabolism, oxidative stress, and inflammation, which can eventually lead to the disordered function of macrophages, vascular smooth muscle cells, and vascular endothelial cells. However, the molecular pathways through which ferroptosis affects AS development and progression are not entirely understood. This review systematically summarizes the interactions between AS and ferroptosis and provides a feasible approach for inhibiting AS progression from the perspective of ferroptosis.

Wound recovery efficacy of retinol based-micellar formulations in an organotypic skin wound model.

Impairment of the skin's structural integrity initially results in acute wounds which can become chronic if timely wound closure is not achieved. Chronic wounds (CWs) affect more than 1% of the global population with increasing cases of this condition due to the ageing population. Current wound management relies on debridement, hyperbaric oxygen, antibiotics, and wound dressings, which lack early intervention and specificity. Herein, antibiotics-free retinol-based micellar formulations (RMF) were made and their wound healing efficacy were investigated in vitro. Five different formulations with retinol contents of 0.3% and 1% against a placebo were topically applied to an organotypic full-thickness skin wound model (FT-SWM, MatTek®) with a 3 mm punch wound, and maintained in an incubator for 6 days. The histological analysis of the FT-SWM was conducted at depths of 60 µm and 80 µm. It was found that all the micellar retinol formulations accelerated wound bed contraction, with 0.3% RMF demonstrating the highest efficacy. At the depths of 60 µm and 80 µm, the 0.3% RMF exhibited inner wound diameter contraction of 58% and 77%, respectively, in comparison to the placebo showing 15% and 8%. The RMF significantly accelerated wound healing and can thus be a potential early intervention for speedy wound recovery. It should be pointed out that these results were obtained based on a small sample size and a large sample size will be explored to further validate the results.