Exploring the latent cognitive structure in schizophrenia: implications for antipsychotic treatment responses.

BACKGROUND: Individuals diagnosed with schizophrenia present diverse degrees and types of cognitive impairment, leading to variations in responses to antipsychotic treatments. Understanding the underlying cognitive structures is crucial for assessing this heterogeneity. Utilizing latent profile analysis (LPA) enables the delineation of latent categories of cognitive function. Integrating this approach with a dimensional perspective allows for the exploration of the relationship between cognitive function and treatment response. METHODS: This study examined 647 patients from two distinct cohorts. Utilizing LPA within the discovery cohort (n = 333) and the replication cohort (n = 314), latent subtypes were identified categorically. The stability of cognitive structures was evaluated employing Latent Transition Analysis (LTA). The relationship between cognitive function and treatment response were investigated by comparing Positive and Negative Syndrome Scale (PANSS) reduction rates across diverse cognitive subtypes. Furthermore, dimensional insights were gained through correlation analyses between cognitive tests and PANSS reduction rates. RESULTS: In terms of categorical, individuals diagnosed with schizophrenia can be categorized into three distinct subtypes: those 'without cognitive deficit', those 'with mild-moderate cognitive 'eficit', and those 'with moderate-severe cognitive deficit'. There are significant differences in PANSS reduction rates among patients belonging to these subtypes following antipsychotic treatment (p < 0.05). Furthermore, from a dimensional perspective, processing speed at baseline is positively correlated with PANSS score reduction rates at week 8/week 10 (p < 0.01). CONCLUSIONS: Our findings have unveiled the latent subtypes of cognitive function in schizophrenia, illuminating the association between cognitive function and responses to antipsychotic treatment from both categorical and dimensional perspectives.

Orlistat for the treatment of antipsychotic-induced weight gain: an eight-week multicenter, randomized, placebo-controlled, double-blind trial.

BACKGROUND: Weight gain and metabolic disorders are commonly induced by antipsychotics. Orlistat is a lipase inhibitor used for weight control. The effect of orlistat on weight gain and metabolic disturbances in people (especially women) treated with antipsychotics has not been sufficiently studied. This study aimed to investigate the efficacy of orlistat in mitigating antipsychotic-induced weight gain and abnormal glycolipid metabolism. METHODS: Patients with schizophrenia or bipolar disorder with a weight gain ≥ 7% after taking antipsychotics were recruited. Participants were randomly allocated to two groups: one received eight weeks of orlistat (360 mg/day) and the other received a placebo. Anthropometric and fasting serum biochemical parameters were measured at baseline, week 4 and week 8. RESULTS: Sixty individuals (orlistat:placebo = 32:28) participated in the study. After controlling for the study center, the eight-week changes in body mass index (BMI), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-CH) and low-density lipoprotein cholesterol (LDL-CH) were significantly different between the groups. According to the mixed linear models, CHOL and LDL-CH were significantly lower in the orlistat group than in the control group at week 8. The week 0-to-8 slopes of BMI, CHOL and LDL-CH were also significantly lower in the orlistat group. CONCLUSIONS: These findings suggested that orlistat is an effective intervention for attenuating weight gain and serum lipid disturbances in antipsychotic-treated patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03451734.

MiR-654-3p targets SRC to suppress tumor growth in non-small cell lung cancer.

Around the world, cancer-related death is primarily caused by lung cancer all the time. MiR-654-3p plays an outstanding role in the development of cancer, but the mechanism of miR-654-3p in non-small cell lung cancer (NSCLC) is uncertain. For this purpose, a quantitative real-time polymerase chain reaction(qRT-PCR) was carried out to detect the expression of miR-654-3p and SRC mRNA. Western blot was used to estimate the level of SRC protein. The mimics enhanced miR-654-3p, while inhibitors knocked it down. Functional experiments were performed to evaluate the proliferation and migration capacities of cells. Flow cytometry assay was utilized to measure apoptosis rates and cell cycles of cells. TargetScan bioinformatics database was queried to identify the probable target gene for miR-654-3p. Dual-fluorescence assay was implemented to verify whether miR-654-3p targets SRC. Subcutaneous tumorigenesis was used to estimate the function of miR-654-3p in vivo. Results showed that low expression of miR-654-3p was found in NSCLC tissues and cells. Up-regulated miR-654-3p suppressed cell proliferation and migration, promoted apoptosis, and blocked cells in the G1 phase, while down-regulated miR-654-3p created the opposite results. Dual-fluorescence assay confirmed that miR-654-3p was directly bound to SRC. Compared with the control group, the effects of miR-654-3p were neutralized in the group, which was co-transfected with miR-654-3p mimics and SRC over-expression plasmids. In vivo, the tumor volume in the LV-miR-654-3p group was smaller than that in the control group. It was concluded that miR-654-3p acts in an anti-cancer role and suppresses tumor progression via regulating SRC, which lays a theoretical foundation for targeted therapy of NSCLC. MiR-654-3p is expected to be a new miRNA-based therapeutic target.

Prevalence and correlates of joint pain among Chinese breast cancer survivors receiving aromatase inhibitor treatment.

BACKGROUND: Aromatase inhibitor (AI)-induced joint pain is a common toxicity of AI treatment. Although many studies have been conducted to examine the occurrence and severity of AI-induced joint pain in breast cancer survivors, none of the studies focused on the Chinese population with breast cancer. Given that the differences in cultural background and the genetic structure between Asians and Caucasians may contribute to different phenotypes of joint pain, this cross-sectional study was therefore conducted to examine the prevalence of AI-induced joint pain among Chinese breast cancer survivors receiving AI treatment and the correlates of pain. METHODS: This cross-sectional study was conducted in a tertiary hospital in China. Breast cancer survivors undergoing AI treatment were recruited to complete the following questionnaires: a self-designed baseline data form, the Nordic Musculoskeletal Questionnaire (NMQ), the Brief Pain Inventory (BPI), the 36-Item Short Form Health Survey (SF-36), and the Functional Assessment of Cancer Therapy-Breast (FACT-B). Based on the assessment results of NMQ (if the participant indicated pain in specific body parts), participants were then invited to complete other questionnaires to specifically assess the joint symptoms, including the Oxford Knee Score (OKS), the Oxford Hip Score (OHS), the Michigan Hand Outcomes Questionnaire (MHQ), and the Manchester Foot Pain Disability Questionnaire (MFPDQ). Descriptive analysis was used to analyse participants' baseline data and the prevalence of pain. Stepwise multiple regression was used to identify the correlates of pain. RESULTS: Four hundred and ten participants were analysed. According to the NMQ, 71.7% of the participants experienced joint symptoms in at least one joint, and the most frequently mentioned joint was knee (39.0%). The diagram in BPI indicated that 28.0% of the participants had the worst pain around knees. In patients with knee pain, the mean OKS score was 40.46 ± 6.19. The sub-scores of BPI for pain intensity and pain interference were 1.30 ± 1.63 and 1.24 ± 1.79, respectively. Patients' poorer physical well-being/functioning, previous use of AI treatment, presence of osteoarthritis, and receiving of physiotherapy were identified as four common correlates of greater severity of pain and pain interference (p < 0.05). CONCLUSIONS: Chinese breast cancer survivors can experience joint pain at various locations, particularly knees. In addition to increasing the use of interventions for pain alleviation, a comprehensive assessment of survivors' conditions such as physical functioning, history of AI treatment, and presence of osteoarthritis should be emphasized to identify survivors who need more attention and tailored interventions.

Novel solid-phase microextraction fiber coatings: A review.

The materials used for the fabrication of solid-phase microextraction fiber coatings in the past five years are summarized in the current review, including carbon, metal-organic frameworks, covalent organic frameworks, aerogel, polymer, ionic liquids/poly (ionic liquids), metal oxides, and natural materials. The preparation approaches of different coatings, such as sol-gel technique, in-situ growth, electrodeposition, and glue methods, are briefly reviewed together with the evolution of the supporting substrates. In addition, the limitations of the current coatings and the future development directions of solid-phase microextraction are presented.

[Evaluation and classification of dissolution behavior and capability of Chinese medicine granules based on an inline turbidity sensor].

In this paper, the inline turbidity sensor technology was used to quantify the turbidity of the solution during the dissolution of Chinese medicine granules. The probe measurement position and the magnetic stirring speed were optimized. As a result, the stirring speed was 400 r·min~(-1), and the probe position was at 1/4 of the diameter of the beaker. The measurement results were accurate and reliable. Totally 105 batches of commercially available Chinese medicine granules were collected and dissolved according to the requirements of the Chinese Pharmacopoeia. At the time point of 5 min, 57 batches of granules were completely dissolved, and the corresponding turbidity values ranged between 0-70 FTU; 32 batches of granules showed a slight turbidity, and the corresponding turbidity values ranged between 70-350 FTU; 14 batches of granule solution were turbid, and the corresponding turbidity values ranged between 350-2 000 FTU; two batches of granule solution were heavily turbid, and the corresponding turbidity values were >2 000 FTU. Among the above results, the number of batches in line with the pharmacopoeia dissolution requirement was 84.76%, and the dissolution of some granules still needed to be improved. The turbidity sensor recorded the change curve of turbidity value over time(solubility behavior curve). The degree of important of disintegration and dissolution during the dissolution process showed disintegration > dissolution, disintegration≈dissolution, disintegration < dissolution. The dissolution behavior of the granules can be classified into three categories. The analysis of the mechanism in the process of granule solubility provides a basis for product process improvement.

Profiling and targeting of cellular mitochondrial bioenergetics: inhibition of human gastric cancer cell growth by carnosine.

L-Carnosine (ß-alanyl-L-histidine) is a naturally occurring dipeptide distributed in various organs of mammalians. We previously showed that carnosine inhibited proliferation of human gastric cancer cells through targeting both mitochondrial bioenergetics and glycolysis pathway. But the mechanism underlying carnosine action on mitochondrial bioenergetics of tumor cells remains unclear. In the current study we investigated the effect of carnosine on the growth of human gastric cancer SGC-7901 cells in vitro and in vivo. We firstly showed that hydrolysis of carnosine was not a prerequisite for its anti-gastric cancer effect. Treatment of SGC-7901 cells with carnosine (20 mmol/L) significantly decreased the activities of mitochondrial respiratory chain complexes I-IV and mitochondrial ATP production, and downregulated 13 proteins involved in mitochondrial bioenergetics. Furthermore, carnosine treatment significantly suppressed the phosphorylation of Akt, while inhibition of Akt activation with GSK690693 significantly reduced the localization of prohibitin-1 (PHB-1) in the mitochondria of SGC-7901 and BGC-823 cells. In addition, we showed that silencing of PHB-1 gene with shRNA markedly reduced the mitochondrial PHB-1 in SGC-7901 cells, and significantly decreased the colony formation capacity and growth rate of the cells. In SGC-7901 cell xenograft nude mice, administration of carnosine (250 mg kg/d, ip, for 3 weeks) significantly inhibited the tumor growth and decreased the expression of mitochondrial PHB-1 in tumor tissue. Taken together, these results suggest that carnosine may act on multiple mitochondrial proteins to down-regulate mitochondrial bioenergetics and then to inhibit the growth and proliferation of SGC-7901 and BGC-823 cells.

Carnosine suppresses oxygen-glucose deprivation/recovery-induced proliferation and migration of reactive astrocytes of rats in vitro.

Glial scar formation resulted from excessive astrogliosis limits axonal regeneration and impairs recovery of function, thus an intervention to ameliorate excessive astrogliosis is crucial for the recovery of neurological function after cerebral ischemia. In this study we investigated the effects of carnosine, an endogenous water-soluble dipeptide (ß-alanyl-L-histidine), on astrogliosis of cells exposed to oxygen-glucose deprivation/recovery (OGD/R) in vitro. Primary cultured rat astrocytes exhibited a significant increase in proliferation at 24 h recovery after OGD for 2 h. Pretreatment with carnosine (5 mmol/L) caused G1 arrest of reactive astrocytes, significantly attenuated OGD/R-induced increase in cyclin D1 protein expression and suppressed OGD/R-induced proliferation of reactive astrocytes. Carnosine treatment also reversed glycolysis and ATP production, which was elevated at 24 h recovery after OGD. A marked increase in migration of reactive astrocytes was observed at 24 h after OGD, whereas carnosine treatment reversed the expression levels of MMP-9 and suppressed the migration of astrocytes. Furthermore, carnosine also improved neurite growth of cortical neurons co-cultured with astrocytes under ischemic conditions. These results demonstrate that carnosine may be a promising candidate for inhibiting astrogliosis and promoting neurological function recovery after ischemic stroke.

Investigation on the potential of waste cooking oil as a grinding aid in Portland cement.

Although there are several methods for managing waste cooking oil (WCO), a significant result has not been achieved in China. A new method is required for safe WCO management that minimizes the environmental threat. In this context, this work was developed in which cement clinker and gypsum were interground with various WCOs, and their properties, such as grindability, water-cement ratio required to achieve a normal consistency, setting times, compressive strength, contents of calcium hydroxide and ettringite in the hardened paste, microstructure and economic and environmental considerations, were addressed in detail. The results show that, overall, WCO favorably improves cement grinding. WCO prolonged the cement setting times and resulted in longer setting times. Additionally, more remarkable effects were found in cements in which WCO contained more unsaturated fatty acid. WCOs increased the cement strength. However, this enhancement was rated with respect to the WCO contents and components. WCOs decreased the CH and AFt contents in the cement hardened paste. Even the AFt content at later ages was reduced when WCO was used. WCO also densify microstructure of the hardened cement paste. It is economically and environmentally feasible to use WCOs as grinding aids in the cement grinding process. These results contribute to the application of WCOs as grinding aids and to the safe management of WCO.

Construction of Conjugated Organic Polymers for Efficient Photocatalytic Hydrogen Peroxide Generation with Adequate Utilization of Water Oxidation.

The visible-light-driven photocatalytic production of hydrogen peroxide (H2O2) is currently an emerging approach for transforming solar energy into chemical energy. In general, the photocatalytic process for producing H2O2 includes two pathways: the water oxidation reaction (WOR) and the oxygen reduction reaction (ORR). However, the utilization efficiency of ORR surpasses that of WOR, leading to a discrepancy with the low oxygen levels in natural water and thereby impeding their practical application. Herein, we report a novel donor-bridge-acceptor (D-B-A) organic polymer conjugated by the Sonogashira-Hagihara coupling reaction with tetraphenylethene (TPE) units as the electron donors, acetylene (A) as the connectors and pyrene (P) moieties as the electron acceptors. Notably, the resulting TPE-A-P exhibits a remarkable solar-to-chemical conversion of 1.65% and a high BET-specific surface area (1132 m2·g-1). Furthermore, even under anaerobic conditions, it demonstrates an impressive H2O2 photosynthetic efficiency of 1770 µmol g-1 h-1, exceeding the vast majority of previously reported photosynthetic systems of H2O2. The outstanding performance is attributed to the effective separation of electrons and holes, along with the presence of sufficient reaction sites facilitated by the incorporation of alkynyl electronic bridges. This protocol presents a successful method for generating H2O2 via a water oxidation reaction, signifying a significant advancement towards practical applications in the natural environment.

Theoretical Domains Framework: A Bibliometric and Visualization Analysis from 2005-2023.

Background: The Theoretical Domains Framework (TDF) is among the most extensively utilised foundational frameworks in implementation science. It was developed from 33 psychological theories, with the latest version identifying 14 domains encompassing 84 theoretical constructs. These domains and constructs capture the complexity of factors that affect behaviours, making the framework a valuable tool for designing and implementing interventions within health and social care settings. Objective: To summarise the development, hot topics, and future trends in TDF-related research and provide implementation practitioners with more information on the application of TDF. Methods: We used TDF as the topic and searched the ISI Web of Science Core Collection, identifying 1382 relevant publications. We used analytical tools such as Excel, Tableau, VOSviewer, and Citespace to conduct a bibliometric analysis of the relevant publication. Results: We identified the United Kingdom as the primary contributor, with University College London as the key institution. Susan Michie ranked highest in total citations. The analysis highlighted cancer and stroke as primary clinic medicine-related topics using TDF. Emerging themes encompass abuse, violence, maternal health, antenatal care, patient involvement, and trauma-informed care et al. "Nurse" and "qualitative research" emerged as recent and enduring hotspots, possibly indicating future research trends. Conclusion: This article represents the first attempt to summarise the TDF using bibliometric analysis. We suggest this method can be used to analyse other theoretical frameworks in scientific implementation of its objectivity and quantifiability. Overall, the application scope of TDF is shifting from public health towards more specialised clinical directions, although its application in the field of public health is continuously expanding. In the future, the number of users of TDF is also expected to expand from implementation scientists to professional technical personnel.

Oxygen-Centered Organic Radicals-Involved Unified Heterogeneous Self-Fenton Process for Stable Mineralization of Micropollutants in Water.

Removing organic micropollutants from water through photocatalysis is hindered by catalyst instability and substantial residuals from incomplete mineralization. Here, a novel water treatment paradigm, the unified heterogeneous self-Fenton process (UHSFP), which achieved an impressive 32% photon utilization efficiency at 470 nm, and a significant 94% mineralization of organic micropollutants-all without the continual addition of oxidants and iron ions is presented. In UHSFP, the active species differs fundamentally from traditional photocatalytic processes. One electron acceptor unit of photocatalyst acquires only one photogenerated electron to convert into oxygen-centered organic radical (OCOR), then spontaneously completing subsequent processes, including pollutant degradation, hydrogen peroxide generation, activation, and mineralization of organic micropollutants. By bolstering electron-transfer capabilities and diminishing catalyst affinity for oxygen in the photocatalytic process, the generation of superoxide radicals is effectively suppressed, preventing detrimental attacks on the catalyst. This study introduces an innovative and cost-effective strategy for the efficient and stable mineralization of organic micropollutants, eliminating the necessity for continuous chemical inputs, providing a new perspective on water treatment technologies.

Hybrid Organic-Inorganic Blast Furnace Slag Binders Activated with Alkali Acetates.

Hybrid organic-inorganic binders based on blast furnace slag were produced using sodium (NaAc) or potassium (KAc) acetate as the sole activator, and their properties were compared with those of sodium- or potassium hydroxide-activated slag pastes. The acetate-activated binders showed significantly lower cumulative heat release and extended setting time (∼230 h) than the hydroxide-activated binders. The main reaction products forming in all binders were calcium aluminosilicate hydrate-type gels and a hydrotalcite-like phase, independently of the activator type used. Compressive strengths of the acetate-activated pastes (∼40 MPa at 180 days) were lower than those of the hydroxide-activated binders (∼80 MPa at 180 days). However, the acetate-based binders exhibited superior impermeability and reduced wettability at 28 days, likely due to hydrophobic acetate groups. It is hypothesized that acetates dissociate in water, forming calcium acetate and alkali silicates via a reaction with species dissolving from the slag. This study demonstrates alkali acetates are effective activators for creating hybrid slag-based binders with reduced permeability.

Achieving a solar-to-chemical efficiency of 3.6% in ambient conditions by inhibiting interlayer charges transport.

Efficiently converting solar energy into chemical energy remains a formidable challenge in artificial photosynthetic systems. To date, rarely has an artificial photosynthetic system operating in the open air surpassed the highest solar-to-biomass conversion efficiency (1%) observed in plants. In this study, we present a three-dimension polymeric photocatalyst achieving a solar-to-H2O2 conversion efficiency of 3.6% under ambient conditions, including real water, open air, and room temperature. The impressive performance is attributed to the efficient storage of electrons inside materials via expeditious intramolecular charge transfer, and the fast extraction of the stored electrons by O2 that can diffuse into the internal pores of the self-supporting three-dimensional material. This construction strategy suppresses the interlayer transfer of excitons, polarizers and carriers, effectively increases the utilization of internal excitons to 82%. This breakthrough provides a perspective to substantially enhance photocatalytic performance and bear substantial implications for sustainable energy generation and environmental remediation.

Microsatellite markers for genotyping of Kodamaea ohmeri: Demonstrating outbreaks based on a multicenter surveillance study in China.

Kodamaea ohmeri, an emerging human pathogen, caused both sporadic and nosocomial infections among immunocompromised people with high mortality. However, there is limited research on the molecular epidemiology of K. ohmeri. A total of fifty microsatellite loci were designed based on K. ohmeri type strain NRRL Y-1932 and three loci were finally selected for microsatellite analysis. Non-duplicated K. ohmeri isolates and strains of other species were collected across China as a part of CHIF-NET program for sensitivity and specificity verification. Antifungal susceptibility was determined using Sensititre YeastOne TM YO10. The three loci (P10, P11 and P26), with a cumulative discriminatory power of 0.98, exhibited a prospective specificity and reproducibility in the PCR of 92 K. ohmeri strains from different hospitals. A total of 54 microsatellite types (MT) were identified and most of them distributed sporadically. However, six strains of MT12 clustered in HZ hospital and were isolated in the same department within two months, indicating a potential outbreak. Of seven isolates exhibited MIC values of >8 mg/L for fluconazole, three isolates from LR hospital shared the same genotype of MT44. Herein, we established a set of microsatellite loci for K. ohmeri, as a rapid and specific tool for genotyping K. ohmeri, and identified several potential clusters. This study will help us better understand the molecular epidemiology of the emerging pathogen K. ohmeri.

Comparative Analysis of Sucrose-Regulatory Genes in High- and Low-Sucrose Sister Clones of Sugarcane.

Sugarcane is a significant primitive source of sugar and energy worldwide. The progress in enhancing the sugar content in sugarcane cultivars remains limited due to an insufficient understanding of specific genes related to sucrose production. The present investigation examined the enzyme activities, levels of reducing and non-reducing sugars, and transcript expression using RT-qPCR to assess the gene expression associated with sucrose metabolism in a high-sucrose sugarcane clone (GXB9) in comparison to a low-sucrose sister clone (B9). Sucrose phosphate synthase (SPS), sucrose phosphate phosphatase (SPP), sucrose synthase (SuSy), cell wall invertase (CWI), soluble acid invertase (SAI), and neutral invertase (NI) are essential enzymes involved in sucrose metabolism in sugarcane. The activities of these enzymes were comparatively quantified and analyzed in immature and maturing internodes of the high- and low-sucrose clones. The results showed that the higher-sucrose-accumulating clone had greater sucrose concentrations than the low-sucrose-accumulating clone; however, maturing internodes had higher sucrose levels than immature internodes in both clones. Hexose concentrations were higher in immature internodes than in maturing internodes for both clones. The SPS and SPP enzymes activities were higher in the high-sucrose-storing clone than in the low-sucrose clone. SuSy activity was higher in the low-sucrose clone than in the high-sucrose clone; further, the degree of SuSy activity was higher in immature internodes than in maturing internodes for both clones. The SPS gene expression was considerably higher in mature internodes of the high-sucrose clones than the low-sucrose clone. Conversely, the SuSy gene exhibited up-regulated expression in the low-sucrose clone. The enhanced expression of SPS in the high-sucrose clone compared to the low-sucrose clone suggests that SPS plays a major role in the increased accumulation of sucrose. These findings provide the opportunity to improve sugarcane cultivars by regulating the activity of genes related to sucrose metabolism using transgenic techniques.

Enhancing Photosynthesis Efficiency of Hydrogen Peroxide by Modulating Side Chains to Facilitate Water Oxidation at Low-Energy Barrier Sites.

Hydrogen peroxide (H2O2) is a crucial oxidant in advanced oxidation processes. In situ, photosynthesis of it in natural water holds the promise of practical application for water remediation. However, current photosynthesis of H2O2 systems primarily relies on oxygen reduction, leading to limited performance in natural water with low dissolved oxygen or anaerobic conditions found in polluted water. Herein, a novel photocatalyst based on conjugated polymers with alternating electron donor-acceptor structures and electron-withdrawing side chains on electron donors is introduced. Specifically, carbazole functions as the electron donor, triazine serves as the electron acceptor, and cyano acts as the electron-withdrawing side chain. Notably, the photocatalyst exhibits a remarkable solar-to-chemical conversion of 0.64%, the highest reported in natural water. Furthermore, even in anaerobic conditions, it achieves an impressive H2O2 photosynthetic efficiency of 1365 µmol g-1 h-1, surpassing all the reported photosynthetic systems of H2O2. This remarkable improvement is attributed to the effective relocation of the water oxidation active site from a high-energy carbazole to a low-energy acetylene site mediated by the side chains, resulting in enhanced O2 or H2O2 generation from water. This breakthrough offers a new avenue for efficient water remediation using advanced oxidation technologies in oxygen-limited environments, holding significant implications for environmental restoration.

Fibroblasts and endothelial cells interplay drives hypertrophic scar formation: Insights from in vitro and in vivo models.

Hypertrophic scar formation is influenced by the intricate interplay between fibroblasts and endothelial cells. In this study, we investigated this relationship using in vitro and in vivo models. Clinical observations revealed distinct morphological changes and increased vascularity at pathological scar sites. Further analysis using OCTA, immunohistochemistry, and immunofluorescence confirmed the involvement of angiogenesis in scar formation. Our indirect co-culture systems demonstrated that endothelial cells enhance the proliferation and migration of fibroblasts through the secretion of cytokines including VEGF, PDGF, bFGF, and TGF-ß. Additionally, a suspended co-culture multicellular spheroid model revealed molecular-level changes associated with extracellular matrix remodeling, cellular behaviors, inflammatory response, and pro-angiogenic activity. Furthermore, KEGG pathway analysis identified the involvement of TGF-ß, IL-17, Wnt, Notch, PI3K-Akt, and MAPK pathways in regulating fibroblasts activity. These findings underscore the critical role of fibroblasts-endothelial cells crosstalk in scar formation and provide potential targets for therapeutic intervention. Understanding the molecular mechanisms underlying this interplay holds promise for the development of innovative approaches to treat tissue injuries and diseases.

Identification of novel therapeutic target and prognostic biomarker in matrix metalloproteinase gene family in pancreatic cancer.

Matrix metalloproteinases (MMPs) play an essential role in various physiological events. Recent studies have revealed its carcinogenic effect in malignancies. However, the different expression patterns, prognostic value, and immunological value of MMPs in pancreatic ductal adenocarcinoma (PDAC) are yet to be comprehensively explored. We utilized Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Omnibus databases to explore the abnormal expression of MMPs in PDAC. Then, Kaplan-Meier survival curve and Cox regression analysis were performed to assess the prognostic value of MMPs. Association between MMPs expression and clinicopathological features was analyzed through UALCAN website. Functional annotations and GSEA analysis were performed to excavate the possible signaling pathways involving prognostic-related MMP. TIMER and TISCH database were used to performed immune infiltration analysis. The expression of prognostic-related MMP in pancreatic cancer cell lines and normal pancreatic cells was detected by Real time quantitative PCR. We observed that 10 MMP genes were consistently up-regulated in GEPIA and GSE62452 dataset. Among them, five highly expressed MMPs (MMP1, MMP3, MMP11, MMP14, MMP28) were closely related to poor clinical outcomes of PDAC patients. Cox regression analysis indicated MMP28 was a risk factor influencing the overall survival of patients. In the clinicopathological analysis, up-regulated MMP28 was significantly associated with higher tumor grade and the mutation status of TP53. GSEA analysis demonstrated that high expression of MMP28 was involved in "interferon_alpha_response" and "P53_pathway". Immune infiltration analysis showed that there was no correlation between MMP28 expression and immune cell infiltration. Single-cell sequencing analysis showed MMP28 has strong correlations with malignant cells and stromal cells infiltration in the tumor microenvironment. And MMP28 was highly expressed in various pancreatic cancer cell lines. In conclusion, MMP28 may represent a potential prognosis biomarker and novel therapeutic molecular targets for PDAC.

RRM2­mediated Wnt/ß­catenin signaling pathway activation in lung adenocarcinoma: A potential prognostic biomarker.

The present study aimed to investigate the role and mechanism of action of ribonucleotide reductase M2 (RRM2) in lung adenocarcinoma and its potential as a therapeutic target. Data of patients with lung adenocarcinoma from The Cancer Genome Atlas database were collected and analyzed to evaluate the potential of RRM2 as a biomarker. The expression of RRM2 was evaluated in the A549 cell line and its cisplatin-resistant A549/DDP cell line derivative by western blot and reverse transcription-quantitative PCR. The study also investigated cell proliferation and the mechanism by which RRM2 controls cellular cisplatin resistance using CCK-8 and colony-formation assays. In addition, cell migration was assessed using Transwell assays, and the cell cycle and apoptosis were examined using flow cytometry. RRM2 was highly expressed in lung adenocarcinoma and was associated with the clinical TMN stage. Functional enrichment analysis showed that RRM2 was enriched in the cell cycle. Immune cell infiltration analysis identified 12 types of immune cell that exhibited differences between patients expressing different levels of RRM2. Cellular assays revealed higher levels of RRM2 expression in A549/DDP cells than A549 cells, and its expression was induced by cisplatin. RRM2 knockdown decreased cell proliferation and migration, accelerated apoptosis and caused cell cycle arrest in the S-phase, increasing the sensitivity of A549 and A549/DDP cells to cisplatin through the Wnt/ß-catenin signaling pathway. Overexpression of ß-catenin reduced the effects of RRM2 knockdown on A549 cells. Lung adenocarcinoma growth may be influenced by RRM2 through the Wnt/ß-catenin signaling pathway, suggesting a potential pathway for cancer progression.