Ultra-sensitive measurement of small optical rotation angles using quantum entanglement based on a quasi-Wollaston prism beam splitter.

The measurement of optical rotation is fundamental to optical atomic magnetometry. Ultra-high sensitivity has been achieved by employing a quasi-Wollaston prism as the beam splitter within a quantum entanglement state, complemented by synchronous detection. Initially, we designed a quasi-Wollaston prism and intentionally rotated the crystal axis of the exit prism element by a specific bias angle. A linearly polarized light beam, incident upon this prism, is divided into three beams, with the intensity of each beam correlated through quantum entanglement. Subsequently, we formulated the equations for optical rotation angles by synchronously detecting the intensities of these beams, distinguishing between differential and reference signals. Theoretical analysis indicates that the measurement uncertainty for optical rotation angles, when using quantum entanglement, exceeds the conventional photon shot noise limit. Moreover, we have experimentally validated the effectiveness of our method. In DC mode, the experimental results reveal that the measurement uncertainty for optical rotation angles is 4.7 × 10-9 rad, implying a sensitivity of 4.7 × 10-10 rad/Hz1/2 for each 0.01 s measurement duration. In light intensity modulation mode, the uncertainty is 48.9 × 10-9 rad, indicating a sensitivity of 4.89 × 10-9 rad/Hz1/2 per 0.01 s measurement duration. This study presents a novel approach for measuring small optical rotation angles with unprecedentedly low uncertainty and high sensitivity, potentially playing a pivotal role in advancing all-optical atomic magnetometers and magneto-optical effect research.

Identifying key inflammatory genes in psoriasis via weighted gene co-expression network analysis: Potential targets for therapy.

Psoriasis is a globally prevalent chronic inflammatory skin disease. This study aimed to scrutinize the hub genes related to inflammation and potential molecular mechanisms in psoriasis. Utilizing mRNA expression profiles from public datasets GSE13355, GSE78097, and GSE14905, we set up a comprehensive analysis. Initially, we selected differentially expressed genes (DEGs) from psoriasis and control samples in GSE13355, followed by calculating inflammatory indices using genomic set variation analysis (GSVA). Weighted gene co-expression network analysis (WGCNA) was then applied to link significant modules with the inflammatory index. This process helped us identify differentially expressed inflammation-related genes (DE-IRGs). A protein-protein interaction (PPI) network was established, with the molecular complex detection (MCODE) plug-in pinpointing six chemokine genes (CCR7, CCL2, CCL19, CXCL8, CXCL1, and CXCL2) as central hub genes. These genes demonstrated pronounced immunohistochemical staining in psoriatic tissues compared to normal skin. Notably, the CCR7 gene exhibited the highest potential for m6A modification sites. Furthermore, we constructed transcription factor-microRNA-mRNA networks, identifying 139 microRNAs and 52 transcription factors associated with the hub genes. For the LASSO logistic regression model, the area under the curve (AUC) in the training set was 1, and in the two validation cohorts GSE78097 and GSE14905 were 1 and 0.872, respectively. In conclusion, our study highlights six chemokine genes (CCR7, CCL2, CCL19, CXCL8, CXCL1, and CXCL2) as potential biomarkers in psoriasis, providing insights into the immune and inflammatory responses as pivotal instances in disease pathogenesis. These findings pave the way for exploring new therapeutic targets, particularly focusing on chemokine-associated pathways in psoriasis treatment.

Classification of Three Anesthesia Stages Based on Near-Infrared Spectroscopy Signals.

Proper monitoring of anesthesia stages can guarantee the safe performance of clinical surgeries. In this study, different anesthesia stages were classified using near-infrared spectroscopy (NIRS) signals with machine learning. The cerebral hemodynamic variables of right proximal oxyhemoglobin (HbO2) in maintenance (MNT), emergence (EM) and the consciousness (CON) stage were collected and then the differences between the three stages were compared by phase-amplitude coupling (PAC). Then combined with time-domain including linear (mean, standard deviation, max, min and range), nonlinear (sample entropy) and power in frequency-domain signal features, feature selection was performed and finally classification was performed by support vector machine (SVM) classifier. The results show that the PAC of the NIRS signal was gradually enhanced with the deepening of anesthesia level. A good three-classification accuracy of 69.27% was obtained, which exceeded the result of classification of any single category feature. These results indicate the fesibility of NIRS signals in performing three or even more anesthesia stage classifications, providing insight into the development of new anesthesia monitoring modalities.

Intrauterine chilled saline instillation reduces endometrial impairment on MRI after ultrasound-guided percutaneous microwave ablation of uterine adenomyosis.

OBJECTIVE: To investigate whether intrauterine chilled saline can reduce endometrial impairment during US-guided percutaneous microwave ablation (PMWA) of adenomyosis. METHODS: An open-label, randomized trial was conducted with sixty symptomatic adenomyosis patients who were randomly assigned (1:1) to receive PMWA treatment assisted by intrauterine saline instillation (study group) or traditional PMWA treatment alone (control group). The primary endpoint was endometrial perfusion impairment grade on post-ablation contrast-enhanced MRI. The secondary endpoints were endometrial dehydration grade, ablation rate, and intra-ablation discomfort. RESULTS: The baseline characteristics of the two groups were similar. The incidence rates of endometrial perfusion impairment on MRI in the study and control groups were 6.7% (2/30) and 46.7% (14/30), respectively (p < 0.001). There were 28 (93.3%), 2 (6.7%), 0, and 0 patients in the study group and 16 (53.3%), 7 (23.3%), 5 (16.7%), and 2 (6.7%) in the control group (p < 0.001) who had grade 0, 1, 2, and 3 perfusion impairment, respectively. Additionally, there were 27 (90%), 3 (10%), and 0 patients in the study group and 19 (63.3%), 10 (33.3%), and 1 (3.3%) in the control group who had grade 0, 1, and 2 endometrial dehydration (p = 0.01). The ablation rates achieved in the study and control groups were 93.3 ± 17% (range: 69.2-139.6%) and 99.7 ± 15.7% (range: 71.5-129.8%), and they were not significantly different (p = 0.14). No significant difference was found in the intra-ablation discomfort. CONCLUSION: Intrauterine chilled saline can effectively reduce endometrial impairment after PMWA treatment for adenomyosis. CRITICAL RELEVANCE STATEMENT: This trial demonstrated that the instillation of intrauterine chilled saline reduced endometrial impairment on MRI during PMWA of adenomyosis. This approach allows more precise and safe ablation in clinical practice. KEY POINTS: Endometrial impairment occurs in the PMWA treatment of adenomyosis. Intrauterine chilled saline can reduce endometrial impairment during PMWA for adenomyosis. An intrauterine catheter is a practical endometrial protecting method during thermal ablation. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100053582. Registered 24 November 2021, www.chictr.org.cn/showproj.html?proj=141090 .

Anthropogenic Disturbances Influenced the Island Effect on Both Taxonomic and Phylogenetic Diversity on Subtropical Islands, Pingtan, China.

The investigation of taxonomic diversity within island plant communities stands as a central focus in the field of island biogeography. Phylogenetic diversity is crucial for unraveling the evolutionary history, ecological functions, and species combinations within island plant communities. Island effects (area and isolation effect) may shape species distribution patterns, habitat heterogeneity affects habitat diversity, and anthropogenic disturbances can lead to species extinction and habitat destruction, thus impacting both species diversity and phylogenetic diversity. To investigate how taxonomic and phylogenetic diversity in island natural plant communities respond to island effects, habitat heterogeneity, and anthropogenic disturbances, we took the main island of Haitan (a land-bridge island) and nine surrounding islands (oceanic islands) of varying sizes as the subjects of our study on the Pingtan islands. We aim to elucidate the influence of island effects, habitat heterogeneity, and anthropogenic disturbances on taxonomic and phylogenetic diversity. The results showed that, (1) Both the taxonomic and phylogenetic diversity of plants on the Pingtan islands followed the island area effect, indicating that as the island area increases, both taxonomic and phylogenetic diversity also increase. (2) Island effects and habitat heterogeneity were found to enhance taxonomic and phylogenetic diversity, whereas anthropogenic disturbances were associated with a decrease in both taxonomic and phylogenetic diversity. Furthermore, the synergistic influence of island effects, habitat heterogeneity, and anthropogenic disturbances collectively exerted a negative impact on both taxonomic and phylogenetic diversity. (3) The contribution of explanatory variables of anthropogenic disturbances for taxonomic and phylogenetic diversity was higher than that of island effects and habitat heterogeneity. Additionally, the contribution of the explanatory variables under the combined influence of island effects, habitat heterogeneity, and anthropogenic disturbances is higher than that of the individual variables for island effects and habitat heterogeneity. These findings suggest that anthropogenic disturbances emerged as the dominant factors influencing both taxonomic and phylogenetic diversity. These findings demonstrate the intricate interplay between island effects, habitat heterogeneity, and anthropogenic disturbances, highlighting their combined influence on both taxonomic and phylogenetic diversity on island.

Natural lignin nanoparticles target tumor by saturating the phagocytic capacity of Kupffer cells in the liver.

Ligand-receptor recognition serves as the fundamental driving force for active targeting, yet it is still constrained by off-target effects. Herein, we demonstrate that circumventing or blocking the mononuclear phagocyte system (MPS) are both viable strategies to address off-target effects. Naturally derived lignin nanoparticles (LNPs) show great potential to block MPS due to its good stability, low toxicity, and degradability. We further demonstrate the impact of LNPs dosage on in vivo tumor targeting and antitumor efficacy. Our results show that a high dose of LNPs (300 mg/kg) leads to significant accumulation at the tumor site for a duration of 14 days after intravenous administration. In contrast, the low-dose counterparts (e.g., 50, 150 mg/kg) result in almost all LNPs accumulating in the liver. This discovery indicates that the liver is the primary site of LNP capture, leaving only the surplus LNPs the chance to reach the tumor. In addition, although cell membrane-engineered LNPs can rapidly penetrate tumors, they are still prone to capture by the liver during subsequent circulation in the bloodstream. Excitingly, comparable therapeutic efficacy is obtained for the above two strategies. Our findings may offer valuable insights into the targeted delivery of drugs for disease treatment.

Hydrogen sulfide maintains mitochondrial homeostasis and regulates ganoderic acids biosynthesis by SQR under heat stress in Ganoderma lucidum.

Hydrogen sulfide (H2S) has recently been recognized as an important gaseous transmitter with multiple physiological effects in various species. Previous studies have shown that H2S alleviated heat-induced ganoderic acids (GAs) biosynthesis, an important quality index of Ganoderma lucidum. However, a comprehensive understanding of the physiological effects and molecular mechanisms of H2S in G. lucidum remains unexplored. In this study, we found that heat treatment reduced the mitochondrial membrane potential (MMP) and mitochondrial DNA copy number (mtDNAcn) in G. lucidum. Increasing the intracellular H2S concentration through pharmacological and genetic means increased the MMP level, mtDNAcn, oxygen consumption rate level and ATP content under heat treatment, suggesting a role for H2S in mitigating heat-caused mitochondrial damage in G. lucidum. Further results indicated that H2S activates sulfide-quinone oxidoreductase (SQR) and complex III (Com III), thereby maintaining mitochondrial homeostasis under heat stress in G. lucidum. Moreover, SQR also mediated the negative regulation of H2S to GAs biosynthesis under heat stress. Furthermore, SQR might be persulfidated under heat stress in G. lucidum. Thus, our study reveals a novel physiological function and molecular mechanism of H2S signalling under heat stress in G. lucidum with broad implications for research on the environmental response of microorganisms.

HSP90ß shapes the fate of Th17 cells with the help of glycolysis-controlled methylation modification.

BACKGROUND AND PURPOSE: Ulcerative colitis (UC) is a refractory inflammatory disease associated with immune dysregulation. Elevated levels of heat shock protein (HSP) 90 in the ß but not α subtype were positively associated with disease status in UC patients. This study validated the possibility that pharmacological inhibition or reduction of HSP90ß would alleviate colitis, induced by dextran sulfate sodium, in mice and elucidated its mechanisms. EXPERIMENTAL APPROACH: Histopathological and biochemical analysis assessed disease severity, and bioinformatics and correlation analysis explained the association between the many immune cells and HSP90ß. Flow cytometry was used to analyse the homeostasis and transdifferentiation of Th17 and Treg cells. In vitro inhibition and adoptive transfer assays were used to investigate functions of the phenotypically transformed Th17 cells. Metabolomic analysis, DNA methylation detection and chromatin immunoprecipitation were used to explore these mechanisms. KEY RESULTS: The selective pharmacological inhibitor (HSP90ßi) and shHSP90ß significantly mitigated UC in mice and promoted transformation of Th17 to Treg cell phenotype, via Foxp3 transcription. The phenotypically-transformed Th17 cells by HSP90ßi or shHSP90ß were able to inhibit lymphocyte proliferation and colitis in mice. HSP90ßi and shHSP90ß selectively weakened glycolysis by stopping the direct association of HSP90ß and GLUT1, the key glucose transporter, to accelerate ubiquitination degradation of GLUT1, and enhance the methylation of Foxp3 CNS2 region. Then, the mediator path was identified as the "lactate-STAT5-TET2" cascade. CONCLUSION AND IMPLICATIONS: HSP90ß shapes the fate of Th17 cells via glycolysis-controlled methylation modification to affect UC progression, which provides a new therapeutic target for UC.

l-Carnosine loaded on carboxymethyl cellulose hydrogels for promoting wound healing.

Wound management remains a challenge in clinical practice. Nowadays, patients have an increasing demand for wound repair with enhanced speed and quality; therefore, there is a great need to seek therapeutic strategies that can promote rapid and effective wound healing. In this study, we developed a carboxymethyl cellulose hydrogel loaded with l-carnosine (CRN@hydrogel) for potential application as a wound dressing. In vitro experiments confirmed that CRN@hydrogel can release over 80% of the drug within 48 h and demonstrated its favorable cytocompatibility and blood compatibility, thus establishing its applicability for safe utilization in clinical practice. Using a rat model, we found that this hydrogel could promote and accelerate wound healing more effectively. These results indicate that the novel hydrogel can serve as an efficient therapeutic strategy for wound treatment.

Injectable cartilage microtissues based on 3D culture using porous gelatin microcarriers for cartilage defect treatment.

Cartilage tissues possess an extremely limited capacity for self-repair, and current clinical surgical approaches for treating articular cartilage defects can only provide short-term relief. Despite significant advances in the field of cartilage tissue engineering, avoiding secondary damage caused by invasive surgical procedures remains a challenge. In this study, injectable cartilage microtissues were developed through 3D culture of rat bone marrow mesenchymal stem cells (BMSCs) within porous gelatin microcarriers (GMs) and induced differentiation. These microtissues were then injected for the purpose of treating cartilage defects in vivo, via a minimally invasive approach. GMs were found to be noncytotoxic and favorable for cell attachment, proliferation and migration evaluated with BMSCs. Moreover, cartilage microtissues with a considerable number of cells and abundant extracellular matrix components were obtained from BMSC-laden GMs after induction differentiation culture for 28 days. Notably, ATDC5 cells were complementally tested to verify that the GMs were conducive to cell attachment, proliferation, migration and chondrogenic differentiation. The microtissues obtained from BMSC-laden GMs were then injected into articular cartilage defect areas in rats and achieved superior performance in alleviating inflammation and repairing cartilage. These findings suggest that the use of injectable cartilage microtissues in this study may hold promise for enhancing the long-term outcomes of cartilage defect treatments while minimizing the risk of secondary damage associated with traditional surgical techniques.

In utero aspirin exposure and child neurocognitive development: A propensity score-matched analysis.

OBJECTIVE: To evaluate the association between a short-period, high-dose in utero aspirin exposure and child neurocognitive development. DESIGN: A propensity score-matched analysis of a multicentre prospective cohort study. SETTING: The US Collaborative Perinatal Project (1959-1976). POPULATION: A total of 50 565 singleton live births with maternal information. METHODS: We performed a propensity score matching to balance maternal characteristics between women with and without aspirin exposure. Inverse probability-weighted marginal structural models were used to estimate associations between aspirin exposure and child neurocognitive assessments. MAIN OUTCOME MEASURES: Child neurocognitive development was assessed using the Bayley Scales at 8 months, the Stanford Binet Intelligence Scale at 4 years, and the Wechsler Intelligence Scale and Wide-Range Achievement Test (WRAT) at 7 years. RESULTS: Children exposed to aspirin in utero were associated with an 8%-16% reduced risk of having suspect/abnormal or below-average scores in most neurocognitive assessments. A trend of lower risks of having suspect/abnormal or below-average scores was further observed in children with in utero aspirin exposure for more than 7 days, particularly on Bayley Mental (relative risk [RR] 0.82, 95% CI 0.74-0.92), WRAT Reading (RR 0.88, 95% CI 0.78-0.98) and WRAT Arithmetic tests (RR 0.76, 95% CI 0.66-0.86). This association was mainly observed in the second trimester of pregnancy. CONCLUSIONS: In utero aspirin exposure was associated with improved child neurocognitive development in a prospective cohort study. Further studies are warranted to evaluate the impact of long-period and low-dose in utero aspirin exposure on child short- and long-term neurodevelopment.

Biofabrication of Tissue-Engineered Cartilage Constructs Through Faraday Wave Bioassembly of Cell-Laden Gelatin Microcarriers.

Acoustic biofabrication is an emerging strategy in tissue engineering due to its mild and fast manufacturing process. Herein, tissue-engineered cartilage constructs with high cell viability are fabricated from cell-laden gelatin microcarriers (GMs) through Faraday wave bioassembly, a typical acoustic "bottom-up" manufacturing process. Assembly modules are first prepared by incorporating cartilage precursor cells, the chondrogenic cell line ATDC5, or bone marrow-derived mesenchymal stem cells (BMSCs), into GMs. Patterned structures are formed by Faraday wave bioassembly of the cell-laden GMs. Due to the gentle and efficient assembly process and the protective effects of microcarriers, cells in the patterned structures maintain high activity. Subsequently, tissue-engineered cartilage constructs are obtained by inducing cell differentiation of the patterned structures. Comprehensive evaluations are conducted to verify chondrocyte differentiation and the formation of cartilage tissue constructs in terms of cell viability, morphological analysis, gene expression, and matrix production. Finally, implantation studies with a rat cartilage defect model demonstrate that these tissue-engineered cartilage constructs are beneficial for the repair of articular cartilage damage in vivo. This study provides the first biofabrication of cartilage tissue constructs using Faraday wave bioassembly, extending its application to engineering tissues with a low cell density.

Combination of anti-SSA/Ro60 and anti-dsDNA serotype is predictive of belimumab renal response in patients with lupus nephritis.

OBJECTIVES: To investigate the effectiveness of belimumab on active lupus nephritis (LN) and explore the predictors, including serological biomarkers, of renal response to belimumab in a real-world setting. METHODS: This multicentre, real-world observational study enrolled patients with active LN receiving intravenous belimumab as an add-on therapy with 24-hour urine protein≥1 g and estimated glomerular filtration rate≥30 mL/min/1.73 m2 at baseline. Complete renal response (CRR), partial renal response (PRR), no renal response (NRR) and primary efficacy renal response (PERR) were evaluated. Multivariable logistic regression was used to identify risk factors for NRR to belimumab at 6 months. RESULTS: Among the 122 patients enrolled, the proportions of patients achieving CRR, PRR, NRR and PERR were 35.9%, 17.1%, 47.0% and 44.4% at 6 months (n=117) and 55.6%, 19.4%, 26.4% and 58.3% at 12 months (n=72), respectively. Proteinuria, daily prednisone dosage and Systemic Lupus Erythematosus Disease Activity Index 2000 scores significantly decreased at 6 and 12 months (p<0.0001). NRR at 6 months (NRR6) was the strongest negative predictor of CRR at 12 months. Baseline anti-dsDNA positivity inversely predicted NRR6 (OR=0.32,95% CI=0.10 to 0.98, p=0.049), while anti-SSA/Ro60 positively predicted NRR6 (OR=3.16, 95% CI=1.14 to 8.74, p=0.027). The combination of anti-SSA/Ro60 and anti-dsDNA serotype quantitatively predicted belimumab renal response. CONCLUSION: The effectiveness of belimumab was reproducible in Chinese patients with active LN. The simple yet interesting serotype predictive model needs further validation and its possible underlying mechanistic relevance deserves further exploration.

UFM1 inhibits hypoxia-induced angiogenesis via promoting proteasome degradation of HIF-1α.

Angiogenesis is crucial for blood flow recovery and ischemic tissue repair of peripheral artery disease (PAD). Exploration of new mechanisms underlying angiogenesis will shed light on the treatment of PAD. Ubiquitin-fold modifier 1 (UFM1), a newly identified ubiquitin-like molecule, has been discovered to be involved in various pathophysiological processes. However, the role of UFM1 in the pathogenesis of PAD, especially in endothelial angiogenesis remains obscure, and we aimed to clarify this issue in this study. We initially found UFM1 was significantly upregulated in gastrocnemius muscles of PAD patients and hind limb ischemia mice. And UFM1 was mainly colocalized with endothelial cells in ischemic muscle tissues. Further, elevated expression of UFM1 was observed in hypoxic endothelial cells. Subsequent genetic inhibition of UFM1 dramatically enhanced migration, invasion, adhesion, and tube formation of endothelial cells under hypoxia. Mechanistically, UFM1 reduced the stability of hypoxia-inducible factor-1α (HIF-1α) and promoted the von Hippel-Lindau-mediated K48-linked ubiquitin-proteasome degradation of HIF-1α, which in turn decreased angiogenic factor VEGFA expression and suppressed VEGFA related signaling pathway. Consistently, overexpression of UFM1 inhibited the angiogenesis of endothelial cells under hypoxic conditions, whereas overexpression of HIF-1α reversed this effect. Collectively, our data reveal that UFM1 inhibits the angiogenesis of endothelial cells under hypoxia through promoting ubiquitin-proteasome degradation of HIF-1α, suggesting UFM1 might serve as a potential therapeutic target for PAD.

Risk prediction model based on machine learning for predicting miscarriage among pregnant patients with immune abnormalities.

Introduction: It is known that patients with immune-abnormal co-pregnancies are at a higher risk of adverse pregnancy outcomes. Traditional pregnancy risk management systems have poor prediction abilities for adverse pregnancy outcomes in such patients, with many limitations in clinical application. In this study, we will use machine learning to screen high-risk factors for miscarriage and develop a miscarriage risk prediction model for patients with immune-abnormal pregnancies. This model aims to provide an adjunctive tool for the clinical identification of patients at high risk of miscarriage and to allow for active intervention to reduce adverse pregnancy outcomes. Methods: Patients with immune-abnormal pregnancies attending Sichuan Provincial People's Hospital were collected through electronic medical records (EMR). The data were divided into a training set and a test set in an 8:2 ratio. Comparisons were made to evaluate the performance of traditional pregnancy risk assessment tools for clinical applications. This analysis involved assessing the cost-benefit of clinical treatment, evaluating the model's performance, and determining its economic value. Data sampling methods, feature screening, and machine learning algorithms were utilized to develop predictive models. These models were internally validated using 10-fold cross-validation for the training set and externally validated using bootstrapping for the test set. Model performance was assessed by the area under the characteristic curve (AUC). Based on the best parameters, a predictive model for miscarriage risk was developed, and the SHapley additive expansion (SHAP) method was used to assess the best model feature contribution. Results: A total of 565 patients were included in this study on machine learning-based models for predicting the risk of miscarriage in patients with immune-abnormal pregnancies. Twenty-eight risk warning models were developed, and the predictive model constructed using XGBoost demonstrated the best performance with an AUC of 0.9209. The SHAP analysis of the best model highlighted the total number of medications, as well as the use of aspirin and low molecular weight heparin, as significant influencing factors. The implementation of the pregnancy risk scoring rules resulted in accuracy, precision, and F1 scores of 0.3009, 0.1663, and 0.2852, respectively. The economic evaluation showed a saving of ¥7,485,865.7 due to the model. Conclusion: The predictive model developed in this study performed well in estimating the risk of miscarriage in patients with immune-abnormal pregnancies. The findings of the model interpretation identified the total number of medications and the use of other medications during pregnancy as key factors in the early warning model for miscarriage risk. This provides an important basis for early risk assessment and intervention in immune-abnormal pregnancies. The predictive model developed in this study demonstrated better risk prediction performance than the Pregnancy Risk Management System (PRMS) and also demonstrated economic value. Therefore, miscarriage risk prediction in patients with immune-abnormal pregnancies may be the most cost-effective management method.

Plasma-based lipidomics reveals potential diagnostic biomarkers for esophageal squamous cell carcinoma: a retrospective study.

Background: Esophageal squamous cell carcinoma (ESCC) is highly prevalent and has a high mortality rate. Traditional diagnostic methods, such as imaging examinations and blood tumor marker tests, are not effective in accurately diagnosing ESCC due to their low sensitivity and specificity. Esophageal endoscopic biopsy, which is considered as the gold standard, is not suitable for screening due to its invasiveness and high cost. Therefore, this study aimed to develop a convenient and low-cost diagnostic method for ESCC using plasma-based lipidomics analysis combined with machine learning (ML) algorithms. Methods: Plasma samples from a total of 40 ESCC patients and 31 healthy controls were used for lipidomics study. Untargeted lipidomics analysis was conducted through liquid chromatography-mass spectrometry (LC-MS) analysis. Differentially expressed lipid features were filtered based on multivariate and univariate analysis, and lipid annotation was performed using MS-DIAL software. Results: A total of 99 differential lipids were identified, with 15 up-regulated lipids and 84 down-regulated lipids, suggesting their potential as diagnostic targets for ESCC. In the single-lipid plasma-based diagnostic model, nine specific lipids (FA 15:4, FA 27:1, FA 28:7, FA 28:0, FA 36:0, FA 39:0, FA 42:0, FA 44:0, and DG 37:7) exhibited excellent diagnostic performance, with an area under the curve (AUC) exceeding 0.99. Furthermore, multiple lipid-based ML models also demonstrated comparable diagnostic ability for ESCC. These findings indicate plasma lipids as a promising diagnostic approach for ESCC.

Optimization of Ti-PA efficiently catalytic the alcoholysis of waste PET using response surface methodology.

A new type of titanium phthalate (Ti-PA) catalyst was prepared by exchange method of phthalic acid and isopropyl titanate, which is never been reported before. The Ti-PA catalyst was characterized by FT-IR, TG, Uv-vis, BET, SEM, and EDS. The Ti-PA catalyst shows good catalytic activity in the alcoholysis reaction of polyethylene terephthalate (PET) and optimal experimental conditions for the alcoholysis process were optimized by response surface methodology; the Ti-PA catalyst provided a BHET yield of 81.98% for reaction lasting 3.98 h at 191 °C of 0.86% catalyst and 13.7 ml ethylene glycol; the model has good reliability. The kinetics and reaction mechanism of the process were explored and apparent activation energy is 75.52 kJ/mol. Finally, the good catalytic activity of Ti-PA was illustrated by comparing it with currently reported catalysts.

Dynamic genomic changes in methotrexate-resistant human cancer cell lines beyond DHFR amplification suggest potential new targets for preventing drug resistance.

BACKGROUND: Although DHFR gene amplification has long been known as a major mechanism for methotrexate (MTX) resistance in cancer, the early changes and detailed development of the resistance are not yet fully understood. METHODS: We performed genomic, transcriptional and proteomic analyses of human colon cancer cells with sequentially increasing levels of MTX-resistance. RESULTS: The genomic amplification evolved in three phases (pre-amplification, homogenously staining region (HSR) and extrachromosomal DNA (ecDNA)). We confirm that genomic amplification and increased expression of DHFR, with formation of HSRs and especially ecDNAs, is the major driver of resistance. However, DHFR did not play a detectable role in the early phase. In the late phase (ecDNA), increase in FAM151B protein level may also have an important role by decreasing sensitivity to MTX. In addition, although MSH3 and ZFYVE16 may be subject to different posttranscriptional regulations and therefore protein expressions are decreased in ecDNA stages compared to HSR stages, they still play important roles in MTX resistance. CONCLUSION: The study provides a detailed evolutionary trajectory of MTX-resistance and identifies new targets, especially ecDNAs, which could help to prevent drug resistance. It also presents a proof-of-principal approach which could be applied to other cancer drug resistance studies.