[Identification and expression of genome of uridine diphosphate glycosyltransferase (UGT) gene family from Chrysanthemum indicum].

Uridine diphosphate glycosyltransferase(UGT) is involved in the glycosylation of a variety of secondary metabolites in plants and plays an important role in plant growth and development and regulation of secondary metabolism. Based on the genome of a diploid Chrysanthemum indicum, the UGT gene family from Ch. indicum was identified by bioinformatics methods, and the physical and chemical properties, subcellular localization prediction, conserved motif, phylogeny, chromosome location, gene structure, and gene replication events of UGT protein were analyzed. Transcriptome and real-time fluorescence quantitative polymerase chain reaction(PCR) were used to analyze the expression pattern of the UGT gene in flowers and leaves of Ch. indicum. Quasi-targeted metabolomics was used to analyze the differential metabolites in flowers and leaves. The results showed that a total of 279 UGT genes were identified in the Ch. indicum genome. Phylogenetic analysis showed that these UGT genes were divided into 8 subfamilies. Members of the same subfamily were distributed in clusters on the chromosomes. Tandem duplications were the main driver of the expansion of the UGT gene family from Ch. indicum. Structural domain analysis showed that 262 UGT genes had complete plant secondary metabolism signal sequences(PSPG box). The analysis of cis-acting elements indicated that light-responsive elements were the most ubiquitous elements in the promoter regions of UGT gene family members. Quasi-targeted metabolome analysis of floral and leaf tissue revealed that most of the flavonoid metabolites, including luteolin-7-O-glucoside and kaempferol-7-O-glucoside, had higher accumulation in flowers. Comparative transcriptome analysis of flower and leaf tissue showed that there were 72 differentially expressed UGT genes, of which 29 genes were up-regulated in flowers, and 43 genes were up-regulated in leaves. Correlation network and phylogenetic analysis showed that CindChr9G00614970.1, CindChr2G00092510.1, and CindChr2G00092490.1 may be involved in the synthesis of 7-O-flavonoid glycosides in Ch. indicum, and real-time fluorescence quantitative PCR analysis further confirmed the reliability of transcriptome data. The results of this study are helpful to understand the function of the UGT gene family from Ch. indicum and provide data reference and theoretical basis for further study on the molecular regulation mechanism of flavonoid glycosides synthesis in Ch. indicum.

Population genetic variation and geographic distribution of suitable areas of Coptis species in China.

Introduction: The rhizomes of Coptis plants have been used in traditional Chinese medicine over 2000 years. Due to increasing market demand, the overexploitation of wild populations, habitat degradation and indiscriminate artificial cultivation of Coptis species have severely damaged the native germplasms of species in China. Methods: Genome-wide simple-sequence repeat (SSR) markers were developed using the genomic data of C. chinensis. Population genetic diversity and structure of 345 Coptis accessions collected from 32 different populations were performed based on these SSRs. The distribution of suitable areas for three taxa in China was predicted and the effects of environmental variables on genetic diversity in relation to different population distributions were further analyzed. Results: 22 primer pairs were selected as clear, stable, and polymorphic SSR markers. These had an average of 16.41 alleles and an average polymorphism information content (PIC) value of 0.664. In the neighbor-joining (N-J) clustering analysis, the 345 individuals clustered into three groups, with C. chinensis, C. chinensis var. brevisepala and C. teeta being clearly separated. All C. chinensis accessions were further divided into four subgroups in the population structure analysis. The predicted distributions of suitable areas and the environmental variables shaping these distributions varied considerably among the three species. Discussion: Overall, the amount of solar radiation, precipitation and altitude were the most important environmental variables influencing the distribution and genetic variation of three species. The findings will provide key information to guide the conservation of genetic resources and construction of a core reserve for species.

A novel long non-coding RNA LINC00524 facilitates invasion and metastasis through interaction with TDP43 in breast cancer.

Breast cancer (BC) remains a significant health concern worldwide, with metastasis being a primary contributor to patient mortality. While advances in understanding the disease's progression continue, the underlying mechanisms, particularly the roles of long non-coding RNAs (lncRNAs), are not fully deciphered. In this study, we examined the influence of the lncRNA LINC00524 on BC invasion and metastasis. Through meticulous analyses of TCGA and GEO data sets, we observed a conspicuous elevation of LINC00524 expression in BC tissues. This increased expression correlated strongly with a poorer prognosis for BC patients. A detailed Gene Ontology analysis suggested that LINC00524 likely exerts its effects through RNA-binding proteins (RBPs) mechanisms. Experimentally, LINC00524 was demonstrated to amplify BC cell migration, invasion and proliferation in vitro. Additionally, in vivo tests showed its potent role in promoting BC cell growth and metastasis. A pivotal discovery was LINC00524's interaction with TDP43, which leads to the stabilization of TDP43 protein expression, an element associated with unfavourable BC outcomes. In essence, our comprehensive study illuminates how LINC00524 accelerates BC invasion and metastasis by binding to TDP43, presenting potential avenues for therapeutic interventions.

Novel Uncertainty Quantification through Perturbation-Assisted Sample Synthesis.

This paper introduces a novel Perturbation-Assisted Inference (PAI) framework utilizing synthetic data generated by the Perturbation-Assisted Sample Synthesis (PASS) method. The framework focuses on uncertainty quantification in complex data scenarios, particularly involving unstructured data while utilizing deep learning models. On one hand, PASS employs a generative model to create synthetic data that closely mirrors raw data while preserving its rank properties through data perturbation, thereby enhancing data diversity and bolstering privacy. By incorporating knowledge transfer from large pre-trained generative models, PASS enhances estimation accuracy, yielding refined distributional estimates of various statistics via Monte Carlo experiments. On the other hand, PAI boasts its statistically guaranteed validity. In pivotal inference, it enables precise conclusions even without prior knowledge of the pivotal's distribution. In non-pivotal situations, we enhance the reliability of synthetic data generation by training it with an independent holdout sample. We demonstrate the effectiveness of PAI in advancing uncertainty quantification in complex, data-driven tasks by applying it to diverse areas such as image synthesis, sentiment word analysis, multimodal inference, and the construction of prediction intervals.

Isorhamnetin: what is the in vitro evidence for its antitumor potential and beyond?

Isorhamnetin (ISO) is a phenolic compound belonging to flavonoid family, showcasing important in vitro pharmacological activities such as antitumor, anti-inflammation, and organ protection. ISO is predominantly extracted from Hippophae rhamnoides L. This plant is well-known in China and abroad because of its "medicinal and food homologous" characteristics. As a noteworthy natural drug candidate, ISO has received considerable attention in recent years owing to its low cost, wide availability, high efficacy, low toxicity, and minimal side effects. To comprehensively elucidate the multiple biological functions of ISO, particularly its antitumor activities and other pharmacological potentials, a literature search was conducted using electronic databases including Web of Science, PubMed, Google Scholar, and Scopus. This review primarily focuses on ISO's ethnopharmacology. By synthesizing the advancements made in existing research, it is found that the general effects of ISO involve a series of in vitro potentials, such as antitumor, protection of cardiovascular and cerebrovascular, anti-inflammation, antioxidant, and more. This review illustrates ISO's antitumor and other pharmacological potentials, providing a theoretical basis for further research and new drug development of ISO.

Effective oxygen activation on polyoxometalate-based hybrids for epoxidation of alkenes.

Two polyoxometalate-based hybrids, [M(btap)3(H2O)3(HPW12O40)]·xH2O (M-PW, M = Co/Mn, btap = 3,5-bis(1',2',4'-triazol-1'-yl)pyridine) were synthesized. Co-PW exhibited higher activity and selectivity towards olefin epoxidation than Mn-PW due to the synergistic effect between CoII and PW, in which the Co centers activate O2 to ˙O2- and further binding of free H+ from PW affords the active peroxyacid.

Role and regulation of FOXO3a: new insights into breast cancer therapy.

Breast cancer is the most common malignancy in the world, particularly affecting female cancer patients. Enhancing the therapeutic strategies for breast cancer necessitates identifying molecular drug targets that effectively eliminate tumor cells. One of these prominent targets is the forkhead and O3a class (FOXO3a), a member of the forkhead transcription factor subfamily. FOXO3a plays a pivotal role in various cellular processes, including apoptosis, proliferation, cell cycle regulation, and drug resistance. It acts as a tumor suppressor in multiple cancer types, although its specific role in cancer remains unclear. Moreover, FOXO3a shows promise as a potential marker for tumor diagnosis and prognosis in breast cancer patients. In addition, it is actively influenced by common anti-breast cancer drugs like paclitaxel, simvastatin, and gefitinib. In breast cancer, the regulation of FOXO3a involves intricate networks, encompassing post-translational modification post-translational regulation by non-coding RNA (ncRNA) and protein-protein interaction. The specific mechanism of FOXO3a in breast cancer urgently requires further investigation. This review aims to systematically elucidate the role of FOXO3a in breast cancer. Additionally, it reviews the interaction of FOXO3a and its upstream and downstream signaling pathway-related molecules to uncover potential therapeutic drugs and related regulatory factors for breast cancer treatment by regulating FOXO3a.

Zeaxanthin impairs angiogenesis and tumor growth of glioblastoma: An in vitro and in vivo study.

OBJECTIVES: To investigate the therapeutic effects of Zeaxanthin (Zea), one of the oxidized xanthophyll carotenoids belonging to the isoprenoids, on inhibiting the angiogenesis and tumor growth of glioblastoma (GBM) via an in vitro and in vivo study. METHODS: The effects of Zea on the proliferation, adhesion, migration and invasion of human GBM cell lines were detected by cell proliferation assay, cell adhesion assay and Transwell assay. The effect of Zea on angiogenesis was detected by rat aortic ring assay and human umbilical vein endothelial cells (HUVEC) in vitro tube formation assay. The effects of Zea on PARP, Caspase 3 and VEGFR2 phosphorylation as well as VEGFR2's downstream signaling pathway were detected by Western blot. The in vivo human GBM xenograft mouse model was employed to study the therapeutic efficacy of Zea. RESULTS: Zea impaired the proliferation, adhesion, migration and invasion of U87 and U251 cells as well as HUVECs. Rat aortic ring experiments displayed Zea significantly inhibited angiogenesis during VEGF-induced microvascular germination. In vitro and in vivo vascular experiments verified that Zea inhibited VEGF-induced HUVEC proliferation and capillary-like tube formation. Additionally, Zea induced GBM cells apoptosis via increasing the expression of cleaved PARP and Caspase 3. In HUVECs and U251 GBM cells, Zea down-regulated VEGF-induced activation of the VEGFR2 kinase pathway. Meanwhile the expression of p-AKT, p-ERK, p-STAT3 and FAK were all attenuated in U251 cells. Moreover, the effects of Zea on GBM cells proliferation could be blocked by VEGFR2 kinase inhibitor SU5408. These results suggest that Zea may hinder GBM angiogenesis and tumor growth through down-regulating a cascade of oncogenic signaling pathways, both through the inhibition of angiogenesis and the anti-tumor mechanism of a direct cytotoxic effect. Besides, Zea inhibits GBM angiogenesis and tumor growth exemplified through a xenograft mouse model in vivo. CONCLUSION: Zea impairs angiogenesis and tumor growth of GBM both in vitro and in vivo. It can be declared that Zea is a potential valuable anticancer candidate for the future treatment strategy of GBM.

A novel heterozygous frameshift mutation in the KRT6A gene responsible for an uncommon phenotype of pachyonychia congenita: One case report and review of literature.

Pachyonychia congenita is an uncommon autosomal dominant skin disorder characterized by hypertrophic nail dystrophy, palmoplantar keratoderma, oral leukokeratosis, and cutaneous cysts. And fissured tongue is rarely reported in patients with pachyonychia congenita. The disease is primarily associated with mutations in five keratin genes, namely KRT6A, KRT6B, KRT6C, KRT16 or KRT17. Herein we report a 9-year-old Chinese girl who has thickened nails, keratinized plaques, and fissured tongue since birth. To investigate the underlying genetic cause, whole-exome sequencing and Sanger sequencing were performed in this patient and her family members. We identified a candidate variant c.1460-2_1460del (p.S487Lfs*21) in the KRT6A gene (NM_005554.4) by whole-exome sequencing. Sanger sequencing revealed the absence of the mutation in both parents, indicating that it is a de novo variant. Thus, the novel heterozygous frameshift mutation c.1460-2_1460del (p.S487Lfs*21) within exon 9 of KRT6A was identified as the genetic cause of the patient. Our study identified a rare de novo heterozygous frameshift mutation in the KRT6A gene in a patient with pachyonychia congenita presenting fissured tongue. Our findings expand the KRT6A gene mutation spectrum of Pachyonychia congenita, and will contribute to the future genetic counseling and gene therapy for this disease.

Evaluating the comprehensive diagnosis efficiency of lung cancer, including measurement of SHOX2 and RASSF1A gene methylation.

Methylation of the promoters of SHOX2 and RASSF1A (LungMe®) exhibits promise as a potential molecular biomarker for diagnosing lung cancer. This study sought to assess the aberrant methylation of SHOX2 and RASSF1A in broncho-exfoliated cells (BEC) and compare it with conventional cytology, histology examination, immunohistochemistry, and serum tumor markers to evaluate the overall diagnostic efficiency for lung cancer. This study recruited 240 patients, including 185 malignant cases and 55 benign cases. In our observation, we noted a slight reduction in the detection sensitivity, however, the ΔCt method exhibited a significant enhancement in specificity when compared to Ct judgment. Consequently, the ΔCt method proves to be a more appropriate approach for interpreting methylation results. The diagnostic sensitivity of cytology and histology was in ranged from 20.0%-35.1% and 42.9%-80%, respectively, while the positive detection rate of LungMe® methylation ranged from 70.0% to 100%. Additionally, our findings indicate a higher prevalence of SHOX2( +) among patients exhibiting medium and high expression of Ki67 (P < 0.01), as opposed to those with low expression of Ki67, but RASSF1A methylation did not show this phenomenon (P = 0.35). Furthermore, CEA, SCCA, and CYFRA21-1 showed positive detection rates of 48.8%, 26.2%, and 55.8%, respectively. Finally, we present a comprehensive lung cancer diagnostic work-up, including LumgMe® methylation. The combined analysis of SHOX2 and RASSF1A methylation serves as a powerful complement and extension to conventional methods, enhancing the accuracy of a lung cancer diagnosis with satisfactory sensitivity and specificity.

A Pilot Study to Explore the Effect of Long Acting Injectable Antipsychotics on Aggression.

Objectives: To explore the effect of switching from an oral antipsychotic to a long-acting injectable (LAI) antipsychotic on aggression, in terms of the changes of verbal and physical aggression, interventions required, self-injurious behavior, use of seclusion or restraint, antipsychotic medication refusal, and use of antipsychotics as needed (PRN). Methods: This was a retrospective chart review at a long-term state forensic psychiatric facility. Patients treated with an oral antipsychotic for at least 6 months and then switched to a LAI antipsychotic for an additional 6 months during an 80-month period were included. Results: Out of 70 patients evaluated, 18 were the study subjects. The median age of the cohort was 38 years with a majority being male. Of the seven patients who had an incident of aggression, two had an increase in aggressive incidents following the switch, three had a decrease, and two had no change. Thirty-six interventions occurred while patients were on an oral antipsychotic, which decreased by 30.6% to 25 interventions after the switch. Three patients had an incident of self-injurious behavior, and 6 patients required restraints/seclusions. Of the eight patients who had retrievable medication refusal and antipsychotic PRN use information, five had a decrease in antipsychotic medication refusals and five had an increase in PRN antipsychotic use after the switch. Conclusion: The switch from an oral antipsychotic to a LAI antipsychotic did not appear to significantly increase or decrease incidents of aggression or self-injurious behavior, but seemed to decrease the number of restraints/seclusions required.

ORTEGA v1.0: an open-source Python package for context-aware interaction analysis using movement data.

BACKGROUND: Interaction analysis via movement in space and time contributes to understanding social relationships among individuals and their dynamics in ecological systems. While there is an exciting growth in research in computational methods for interaction analysis using movement data, there remain challenges regarding reproducibility and replicability of the existing approaches. The current movement interaction analysis tools are often less accessible or tested for broader use in ecological research. RESULTS: To address these challenges, this paper presents ORTEGA, an Object-oRiented TimE-Geographic Analytical tool, as an open-source Python package for analyzing potential interactions between pairs of moving entities based on the observation of their movement. ORTEGA is developed based on one of the newly emerged time-geographic approaches for quantifying space-time interaction patterns among animals. A case study is presented to demonstrate and evaluate the functionalities of ORTEGA in tracing dynamic interaction patterns in animal movement data. Besides making the analytical code and data freely available to the community, the developed package also offers an extension of the existing theoretical development of ORTEGA for incorporating a context-aware ability to inform interaction analysis. CONCLUSIONS: ORTEGA contributes two significant capabilities: (1) the functions to identify potential interactions (e.g., encounters, concurrent interactions, delayed interactions) from movement data of two or more entities using a time-geographic-based approach; and (2) the capacity to compute attributes of potential interaction events including start time, end time, interaction duration, and difference in movement parameters such as speed and moving direction, and also contextualize the identified potential interaction events.

Mechanical characterization and water stability of loess improved by bio-based materials: An eco-friendly approach.

Loess exhibits poor engineering properties, such as low strength and poor water stability. Conventional materials used for improving loess, such as cement and lime, result in environmental pollution issues throughout their production and application processes. To assess the efficacy of bio-based materials, including calcium alginate (CA), xanthan gum (XA), cotton fibers (CO) and flax fibers (FA) in the treatment of loess, the improved soil's strength, disintegration, and water resistance were examined. Subsequently, an optimal amendment approach was determined, and dry-wet cycle tests and microscopic observation were performed. The results show that 1.0 % calcium alginate can effectively enhance the strength of loess, significantly improving its resistance to disintegration with almost no observable disintegration; permeability is significantly reduced, and water repellency is enhanced. 2.0 % xanthan can improve the strength and disintegration resistance of loess, but the improvement in strength is lower than that of calcium alginate. Additionally, the improved soil with XA experiences a flocculent disintegration in static water, which cannot maintain the soil structure. Cotton fibers and flax fibers can enhance both compressive and tensile strength of the soil. The content of 0.45 % flax fibers is considered the optimal choice as it has no effect on water stability. Combining the above results, the combination of 1.0 % CA and 0.45 % FA has been selected to improve the loess, which effectively improves the comprehensive mechanical properties and water stability of the composite improved soil. The decrease in strength and mass loss rate are significantly reduced after dry-wet cycle tests. Microscopic tests show that calcium alginate connects soil particles by Ca2+ ionic bridges, which allows the cementing materials to fill the loess pores and exert the role of agglomeration and coagulation to enhance the integrity of the loess. This study shows that the bio-based material with calcium alginate as the main body can effectively improve the mechanical strength and water stability of the loess.

Deciphering the heterogeneity of neutrophil cells within circulation and the lung cancer microenvironment pre- and post-operation.

Neutrophils play a crucial role in the immune system within tumor microenvironment. At present, numerous studies have explored the changes of neutrophils' automatic killing effect and cellular communication with other immune cells under pathological conditions through single-cell sequencing. However, there remains a lack of definite conclusion about the identification criteria of neutrophil subgroups. Here, we collected tumor and para-carcinoma tissues, pre- and postoperative blood from patients with non-small cell lung cancer (NSCLC), and performed single-cell RNA (scRNA) sequencing to evaluate the distribution of neutrophil subgroups. We have developed a computational method of over expression rate (OER) to evaluate the specificity of neutrophil subgroups, in order to target gene panels with potential clinical application value. In addition, OER was used to evaluate specificity of neutrophil subsets in healthy people and patients with various diseases to further validate the feasibility of this evaluation system. As a result, we found the specificity of Neu_ c1_ IL1B and Neu_ c2_ cxcr4 (low) in postoperative blood has increased, while that of IL-7R + neutrophils has decreased, indicating that these groups of cells possibly differentiated or migrated to other subgroups in the state of lung cancer. In addition, seven gene panels (Neu_c3_CST7, RSAD2_Neu, S100A2/Pabpc1_Neu, ISG15/Ifit3_Neu, CD74_Neu, PTGS2/Actg1_Neu, SPP1_Neu) were high specific in all the four NSCLC-associated samples, meaning that changes in the percentage of these cell populations would have a high degree of confidence in assessing changes of disease status. In conclusion, combined consideration of the distribution characteristics of neutrophil subgroups could help evaluate the diagnosis and prognosis of NSCLC.

Analyzing tiger interaction and home range shifts using a time-geographic approach.

BACKGROUND: Interaction through movement can be used as a marker to understand and model interspecific and intraspecific species dynamics, and the collective behavior of animals sharing the same space. This research leverages the time-geography framework, commonly used in human movement research, to explore the dynamic patterns of interaction between Indochinese tigers (Panthera tigris corbeti) in the western forest complex (WEFCOM) in Thailand. METHODS: We propose and assess ORTEGA, a time-geographic interaction analysis method, to trace spatio-temporal interactions patterns and home range shifts among tigers. Using unique GPS tracking data of tigers in WEFCOM collected over multiple years, concurrent and delayed interaction patterns of tigers are investigated. The outcomes are compared for intraspecific tiger interaction across different genders, relationships, and life stages. Additionally, the performance of ORTEGA is compared to a commonly used proximity-based approach. RESULTS: Among the 67 tracked tigers, 42 show concurrent interactions at shared boundaries. Further investigation of five tigers with overlapping home ranges (two adult females, a male, and two young male tigers) suggests that the mother tiger and her two young mostly stay together before their dispersal but interact less post-dispersal. The male tiger increases encounters with the mother tiger while her young shift their home ranges. On another timeline, the neighbor female tiger mostly avoids the mother tiger. Through these home range dynamics and interaction patterns, we identify four types of interaction among these tigers: following, encounter, latency, and avoidance. Compared to the proximity-based approach, ORTEGA demonstrates better detects concurrent mother-young interactions during pre-dispersal, while the proximity-based approach misses many interactions among the dyads. With larger spatial buffers and temporal windows, the proximity-based approach detects more encounters but may overestimate the duration of interaction. CONCLUSIONS: This research demonstrates the applicability and merits of ORTEGA as a time-geographic based approach to animal movement interaction analysis. We show time geography can develop valuable, data-driven insights about animal behavior and interactions. ORTEGA effectively traces frequent encounters and temporally delayed interactions between animals, without relying on specific spatial and temporal buffers. Future research should integrate contextual and behavioral information to better identify and characterize the nature of species interaction.

Impact of COVID-19 quarantines on clozapine-induced constipation: Experience of utilizing a clozapine-induced constipation protocol at a state forensic psychiatric facility.

Objective: Since 2017, Fulton State Hospital (FSH) has implemented a clozapine-induced constipation protocol. In March 2020, FSH initiated unit quarantines to minimize the spread of coronavirus disease (COVID-19). The objective of this study was to evaluate the impact of these quarantines on medical referrals for constipation, the Bristol Stool Chart ratings, utilization of as-needed (PRN) laxatives, and adherence rates with scheduled constipation medication regimens. Methods: Patients on the clozapine-induced constipation protocol from May 1, 2019 to December 31, 2020, were included, with 10-month pre- and mid-quarantine implementation. Data collected included patient demographics, primary psychiatric diagnosis, and outcome variables. Descriptive statistics and paired t-tests were performed. Results: A total of 31 patients were included. Most were male (93.5%), with a median age of 40 years. The most common primary diagnosis was schizophrenia. Compared with the pre-quarantine implementation period, there were fewer medical referral contacts per person, less use of PRN laxatives, and slightly lower adherence rates to scheduled constipation medication regimens during the mid-quarantine implementation period. Conclusion: Compared with the pre-quarantine implementation period, there were fewer medical referrals per person during the mid-quarantine implementation period.

Tobacco market trends in 97 countries between 2007 and 2021.

INTRODUCTION: Analysis of the tobacco market can provide valuable insights for developing tobacco control strategies. This study examines the market trends of cigarettes, cigars/cigarillos, smoking tobacco, smokeless tobacco, e-cigarettes, heated tobacco products (HTPs), and tobacco-free oral nicotine, across 97 countries between 2007 and 2021. METHODS: We obtained annual tobacco retail value data from Euromonitor Passport and calculated the market share for each type of tobacco product. The research examined trends in retail value and market share globally, stratified by national income level, as well as in individual countries. RESULTS: From 2007 to 2015, the growth of the global tobacco market was primarily driven by cigarette sales. However, starting in 2016, emerging products, including e-cigarettes, HTPs, and tobacco-free oral nicotine, as well as non-cigarette combustible products, including cigars/cigarillos and smoking tobacco, have been mostly responsible for the increases in the global tobacco retail value. High-income countries experienced the greatest increase in the retail value of emerging products, while middle- and low-income countries still observed rises in cigarette sales. CONCLUSIONS: Trends in the retail value of different tobacco products varied widely during the study period, with distinct trends observed in different income levels and within individual countries. These trends can supplement prevalence data and be used to inform local tobacco control policies.

Multifunctional biomimetic hydrogel dressing provides anti-infection treatment and improves immunotherapy by reprogramming the infection-related wound microenvironment.

The advancement of biomaterials with antimicrobial and wound healing properties continues to present challenges. Macrophages are recognized for their significant role in the repair of infection-related wounds. However, the interaction between biomaterials and macrophages remains complex and requires further investigation. In this research, we propose a new sequential immunomodulation method to enhance and expedite wound healing by leveraging the immune properties of bacteria-related wounds, utilizing a novel mixed hydrogel dressing. The hydrogel matrix is derived from porcine acellular dermal matrix (PADM) and is loaded with a new type of bioactive glass nanoparticles (MBG) doped with magnesium (Mg-MBG) and loaded with Curcumin (Cur). This hybrid hydrogel demonstrates controlled release of Cur, effectively eradicating bacterial infection in the early stage of wound infection, and the subsequent release of Mg ions (Mg2+) synergistically inhibits the activation of inflammation-related pathways (such as MAPK pathway, NF-κB pathway, TNF-α pathway, etc.), suppressing the inflammatory response caused by infection. Therefore, this innovative hydrogel can safely and effectively expedite wound healing during infection. Our design strategy explores novel immunomodulatory biomaterials, offering a fresh approach to tackle current clinical challenges associated with wound infection treatment.

The ERK-cPLA2-ACSL4 axis mediating M2 macrophages ferroptosis impedes mucosal healing in ulcerative colitis.

Ulcerative colitis (UC) is a chronic gastrointestinal disease that can be managed with 5-aminosalicylic acid (5-ASA), the standard treatment for UC. However, the effectiveness of 5-ASA is not always optimal. Our study revealed that despite 5-ASA treatment, cells continued to experience excessive ferroptosis, which may hinder mucosal healing in UC and limit the success of this treatment approach in achieving disease remission. We found that combining 5-ASA with the ferroptosis inhibitor Fer-1 led to a significant inhibition of ferroptosis in macrophages present in the colon tissue, along with an increase in the proportion of M2 macrophages, suggesting that targeting ferroptosis in M2 macrophages could be a potential therapeutic strategy for alleviating UC. Our study also demonstrated that M2 macrophages are more susceptible to ferroptosis compared to M1 macrophages, and this susceptibility is associated with the activated arachidonic acid (AA) metabolism pathway mediated by ERK-cPLA2-ACSL4. Additionally, we found that the expression of cPLA2 gene pla2g4a was increased in the colon of UC patients compared to healthy controls. Furthermore, targeted metabolomics analysis revealed that the combination treatment group, as opposed to the 5-ASA treatment group, exhibited the ability to modulate AA metabolism. Overall, our findings emphasize the importance of addressing macrophage ferroptosis in order to enhance macrophage anti-inflammation, improve mucosal healing, and achieve better therapeutic outcomes for patients with UC.