Laccase-induced decontamination and humification mechanisms of estrogen in water-crop matrices.

Enzymatic humification plays a crucial biogeochemical role in eliminating steroidal estrogens and expanding organic carbon stocks. Estrogenic contaminants in agroecosystems can be taken up and acropetally translocated by crops, but the roles of laccase-triggered rhizospheric humification (L-TRH) in pollutant dissipation and plant uptake remain poorly understood. In this study, the laccase-induced decontamination and humification mechanisms of 17ß-estradiol (E2) in water-crop media were investigated by performing greenhouse pot experiments with maize seedlings (Zea mays L.). The results demonstrated that L-TRH effectively dissipated E2 in the rhizosphere solution and achieved the kinetic constants of E2 dissipation at 10 and 50 µM by 8.05 and 2.75 times as much as the treatments without laccase addition, respectively. The copolymerization of E2 and root exudates (i.e. phenols and amino acids) consolidated by L-TRH produced a larger amount of humified precipitates with the richly functional carbon architectures. The growth parameters and photosynthetic pigment levels of maize seedlings were greatly impeded after a 120-h exposure to 50 µM E2, but L-TRH motivated the detoxication process and thus mitigated the phytotoxicity and bioavailability of E2. The tested E2 contents in the maize tissues initially increased sharply with the cultivation time but decreased steadily. Compared with the treatment without laccase addition, the uptake and accumulation of E2 in the maize tissues were obviously diminished by L-TRH. E2 oligomers such as dimer, trimer, and tetramer recognized in the rhizosphere solution were also detected in the root tissues but not in the shoots, demonstrating that the acropetal translocation of E2 oligomers was interrupted. These results highlight a promising strategy for decontaminating estrogenic pollutants, boosting rhizospheric humification, and realizing low-carbon emissions, which would be beneficial for agroenvironmental bioremediation and sustainability.

Real-world data on the first-line immune checkpoint inhibitors or in combination with chemotherapy in older patients (aged ≥ 75 years) with advanced non-small cell lung cancer.

Purpose: The purpose of this study is to investigate the efficacy and safety of immune checkpoint inhibitors (ICIs) or plus with chemotherapy in older patients. Methods: We enrolled 110 older patients with non-small cell lung cancer (NSCLC ≥75 years) who received either chemotherapy alone (chemo), ICI plus chemotherapy (ICI + chemo), or ICI alone and ICI plus other therapies, which included anti-angiogenesis drugs or other novel ICI (ICIs). Patient characteristics, treatment response, survival, and toxicity were evaluated. Results: In total population, the ICIs group has the highest disease control rate (DCR 75%). There were no significant differences in progression-free survival (PFS) and overall survival (OS) among older patients between ICI + chemo and ICIs groups (PFS: 5.3 months vs. 5.5 months, p = 0.70, OS: 10.7 months vs. 20.3 months, p = 0.995). Meanwhile, we observed ICIs had a longer PFS and OS than chemo group (PFS: 3.9 months vs. 5.5 months, p = 0.01, OS: 10.9 months vs. 20.3 months, p = 0.05). Subgroup analysis showed that patients with programmed death ligand-1 (PD-L1) ≥ 1% had a distinct longer trend toward OS in ICIs group compared to ICI + chemo group (22.4 months vs. 10.7 months, p = 0.605), even though there was no significant difference. In terms of safety, ICIs was more tolerable and had a lower discontinuation rate than ICI + chemo group. Conclusion: In the real world, ICI + chemo is more likely to be discontinued due to adverse effects and does not significantly improve patient survival compared with ICIs treatment in total population and subgroup. Therefore, ICI alone or ICIs plus other therapies, such as anti-angiogenesis drugs or other novel ICI (ICIs) could be recommended for older cases with PD-L1 positive NSCLC.

Nivolumab combined docetaxel versus nivolumab in patients with previously treated nonsmall cell lung cancer: a phase 2 study.

The current standard second-line treatment is immune checkpoint inhibitors monotherapy for nonsmall cell lung cancer (NSCLC) patients. The objective of this phase 2 study was to evaluate the efficacy and safety of nivolumab plus docetaxel compared with nivolumab monotherapy for second-line therapy in immunotherapy-naive patients with advanced NSCLC. Progression-free survival (PFS) was the primary endpoint of this phase 2 study. Patients were randomized to receive nivolumab plus docetaxel or nivolumab monotherapy. From July 2019 to June 2022, a total of 22 patients were recruited, with significantly longer median PFS observed in the nivolumab plus docetaxel group (4.0 months) compared to the nivolumab group (2.0 months), P  = 0.0019. The study was closed in June 2022 due to slow recruitment. The objective response rate was 10.0% [95% confidence interval (CI), 0-28.6] in the nivolumab group and 25% (95% CI, 0.5-49.5) in the nivolumab + docetaxel group ( P  = 0.346). Disease control was significantly higher in the nivolumab plus docetaxel arm (40.0% versus 83.3%, P  = 0.035). There was also an improvement in overall survival (OS) in the nivolumab + docetaxel arm, but this was not statistically significant (10.0 months versus 7.2 months, P  = 0.129). The addition of docetaxel to nivolumab was well-tolerated, with adverse events more common in the combination group. Despite the small sample size, the results suggest that the addition of docetaxel to nivolumab may be a promising treatment option for NSCLC patients progressing on platinum-based chemotherapy, with trends towards improved OS observed.

Epidemiology and drug resistance analysis of bloodstream infections in an intensive care unit from a children's medical center in Eastern China for six consecutive years.

BACKGROUND: Children in the intensive care unit (ICU) who suffer from severe basic diseases and low immunity are usually in critical condition. It is crucial to assist clinicians in selecting the appropriate empirical antibiotic therapies for clinical infection control. METHODS: We retrospectively analyzed data from 281 children with bloodstream infection (BSI). Comparisons of basic data, pathogenic information, and drug resistance of the main bacteria were conducted. RESULTS: We detected 328 strains, including Gram-positive bacteria (223, 68%), mainly coagulase-negative Staphylococci (CoNS); Gram-negative bacteria (91, 27.7%); and fungi (14, 4.3%). The results of the binary logistic regression analysis showed that the main basic disease was an independent risk factor for death. Compared with Escherichia coli, Klebsiella pneumoniae exhibited a higher proportion of extended-spectrum ß-lactamases (ESBLs), and its resistance to some ß-lactamides and quinolones antibiotics were lower. Twenty-seven isolates of multidrug-resistant (MDR) bacteria were detected, of which carbapenem-resistant Acinetobacter baumannii (CRAB) accounted for the highest proportion (13, 48.2%). CONCLUSIONS: CoNS was the principal pathogen causing BSI in children in the ICU of children, and Escherichia coli was the most common Gram-negative pathogen. The main basic disease was an independent risk factor for death. It is necessary to continuously monitor patients with positive blood cultures, pay special attention to detected MDR bacteria, and strengthen the management of antibiotics and prevention and control of nosocomial infections.

Reliability and validity of the Chinese version of the COMPI Fertility Problem Stress Scale-Short Form for infertile women.

OBJECTIVE: To translate and culturally adapt the COMPI Fertility Problem Stress Scale-Short form (COMPI-FPSS-SF) and to test its reliability and validity in China. METHODS: The cross-sectional study adopted Brislin's translation model to translate, synthesize, back-translate, and cross-culturally adapt the COMPI-FPSS-SF for the Chinese setting. A total of 279 infertile women were invited to participate in the study to test the reliability and validity of the scale between March and June 2021. RESULTS: It was verified that the Chinese version of the COMPI-FPSS-SF has three domains with nine items. The Cronbach's α coefficient of the total scale was 0.907, and the coefficient for each dimension ranged from 0.760 to 0.855. The test-retest validity was 0.891. The exploratory factor analysis extracted three common factors with eigenvalues of 4.499, 1.124, and 1.011 and a cumulative variance contribution of 73.706. The validity factor analysis showed good results for the three-factor structure fit. The criterion-related validity with the Fertility Inventory Short-Form Scale was 0.649. The above analysis revealed statistically significant differences (P < 0.001). CONCLUSIONS: The Chinese version of the COMPI-FPSS-SF can be used for the assessment of fertility-related stress in infertility patients in China with good reliability and validity.

A deep learning system for predicting time to progression of diabetic retinopathy.

Diabetic retinopathy (DR) is the leading cause of preventable blindness worldwide. The risk of DR progression is highly variable among different individuals, making it difficult to predict risk and personalize screening intervals. We developed and validated a deep learning system (DeepDR Plus) to predict time to DR progression within 5 years solely from fundus images. First, we used 717,308 fundus images from 179,327 participants with diabetes to pretrain the system. Subsequently, we trained and validated the system with a multiethnic dataset comprising 118,868 images from 29,868 participants with diabetes. For predicting time to DR progression, the system achieved concordance indexes of 0.754-0.846 and integrated Brier scores of 0.153-0.241 for all times up to 5 years. Furthermore, we validated the system in real-world cohorts of participants with diabetes. The integration with clinical workflow could potentially extend the mean screening interval from 12 months to 31.97 months, and the percentage of participants recommended to be screened at 1-5 years was 30.62%, 20.00%, 19.63%, 11.85% and 17.89%, respectively, while delayed detection of progression to vision-threatening DR was 0.18%. Altogether, the DeepDR Plus system could predict individualized risk and time to DR progression over 5 years, potentially allowing personalized screening intervals.

Isoquercitrin attenuates the progression of non-alcoholic steatohepatitis in mice by modulating galectin-3-mediated insulin resistance and lipid metabolism.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a global health problem with no effective treatment. Isoquercitrin (IQ) alters hepatic lipid metabolism and inhibits adipocyte differentiation. The underlying regulatory mechanisms of IQ in regulating insulin resistance (IR) and lipid metabolism remain unclear. PURPOSE: This study was aimed at investigating the effects of IQ on NASH and deciphering whether the underlying mechanisms are via modulation of galectin-3 mediated IR and lipid metabolism. METHODS: IR-HepG2 cell lines were used to demonstrate the ability of IQ to modulate galectin-3-mediated glucose disposal and lipid metabolism. A 20-week high-fat diet (HFD)-induced NASH model was established in C57BL/6J mice, and the protective effect of IQ on lipid disposal in the liver was verified. Further, the mRNA and protein levels of glucose and lipid metabolism were investigated, and lysophosphatidylcholine (LPC) and acylcarnitine (AC) profiling were performed to characterize the changes in endogenous substances associated with mitochondrial function and lipid metabolism in serum and cells. Furthermore, the pharmacokinetic features of IQ were explored in a rat model of NASH. RESULTS: IQ restored liver function and ameliorated inflammation and lipid accumulationin NASH model mice. Notably, significant regulation of the proteins included fatty acid-generating and transporting, cholesterol metabolism enzymes, nuclear transcription factors, mitochondrial metabolism, and IR-related enzymes was noted to be responsible for the therapeutic mechanisms of IQ against experimental NASH. Serum lipid metabolism-related metabolomic assay confirmed that LPC and AC biosynthesis mostly accounted for the therapeutic effect of IQ in mice with NASH and that IQ maintained the homeostasis of LPC and AC levels. CONCLUSION: This is the first study showing that IQ protects against of NASH by modulating galectin-3-mediated IR and lipid metabolism. The mechanisms responsible for liver protection and improved lipid metabolic disorder by IQ may be related to the suppression of IR and regulation of mitochondrial function and lipid metabolism. Galectin-3 down-regulation represents a potentially novel approach for the treatment and prevention of NASH.

Deep learning enables the discovery of a novel cuproptosis-inducing molecule for the inhibition of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers in the world. The therapeutic outlook for HCC patients has significantly improved with the advent and development of systematic and targeted therapies such as sorafenib and lenvatinib; however, the rise of drug resistance and the high mortality rate necessitate the continuous discovery of effective targeting agents. To discover novel anti-HCC compounds, we first constructed a deep learning-based chemical representation model to screen more than 6 million compounds in the ZINC15 drug-like library. We successfully identified LGOd1 as a novel anticancer agent with a characteristic levoglucosenone (LGO) scaffold. The mechanistic studies revealed that LGOd1 treatment leads to HCC cell death by interfering with cellular copper homeostasis, which is similar to a recently reported copper-dependent cell death named cuproptosis. While the prototypical cuproptosis is brought on by copper ionophore-induced copper overload, mechanistic studies indicated that LGOd1 does not act as a copper ionophore, but most likely by interacting with the copper chaperone protein CCS, thus LGOd1 represents a potentially new class of compounds with unique cuproptosis-inducing property. In summary, our findings highlight the critical role of bioavailable copper in the regulation of cell death and represent a novel route of cuproptosis induction.

Unilateral levator avulsion increases the risk of de novo stress urinary incontinence after cystocele repair.

INTRODUCTION: Patients without concurrent baseline stress urinary incontinence (SUI) can develop de novo SUI after transvaginal mesh surgery (TVM) for cystocele repair. Surgeons should be aware of de novo SUI risk factors after TVM. METHODS: A total of 1124 women who were underwent TVM surgeries were recruited and assessed for eligibility from January 1, 2012 to April 30, 2021. All data related to patients and surgeries was collected, which included general conditions, clinical examination, surgery records, and follow-up results. Patients were divided into three groups according to follow-up results and data were compared with each group. The relative risk (RR) of de novo SUI with levator avulsion was also calculated. RESULTS: Three hundred thirty-six patients were included in this study. They were divided into no complication group (n = 249), de novo SUI group (n = 68), and other complications group (n = 19). It seemed elder or obese women had a higher risk of de novo SUI after TVM (p < 0.05). In de novo SUI group, incidence of levator avulsion before surgery were higher than the other two groups (p = 0.001). TVM can significantly change a prolapse to point Aa and Ba on POP-Q quantification system (p < 0.05). RR ratios of de novo SUI with unilateral avulsion group is 2.60 (95% confidence interval [CI] 1.39-4.87), and 2.58 (95%CI 0.82-8.15) for bilateral group. CONCLUSION: Unilateral levator avulsion, instead of bilateral levator avulsion, is a risk factor of de novo SUI after cystocele repair surgery.

Design and implementation of an automatic nursing assessment system based on CDSS technology.

BACKGROUND: Various quantitative and quality assessment tools are currently used in nursing to evaluate a patient's physiological, psychological, and socioeconomic status. The results play important roles in evaluating the efficiency of healthcare, improving the treatment plans, and lowing relevant clinical risks. However, the manual process of the assessment imposes a substantial burden and can lead to errors in digitalization. To fill these gaps, we proposed an automatic nursing assessment system based on clinical decision support system (CDSS). The framework underlying the CDSS included experts, evaluation criteria, and voting roles for selecting electronic assessment sheets over paper ones. METHODS: We developed the framework based on an expert voting flow to choose electronic assessment sheets. The CDSS was constructed based on a nursing process workflow model. A multilayer architecture with independent modules was used. The performance of the proposed system was evaluated by comparing the adverse events' incidence and the average time for regular daily assessment before and after the implementation. RESULTS: After implementation of the system, the adverse nursing events' incidence decreased significantly from 0.43 % to 0.37 % in the first year and further to 0.27 % in the second year (p-value: 0.04). Meanwhile, the median time for regular daily assessments further decreased from 63 s to 51 s. CONCLUSIONS: The automatic assessment system helps to reduce nurses' workload and the incidence of adverse nursing events.

Clinical study of NFNC in the treatment of acute exacerbation chronic obstructive pulmonary disease patients with respiratory failure.

BACKGROUND: Most patients with acute exacerbation chronic obstructive pulmonary disease (AECOPD) have respiratory failure that necessitates active correction and the improvement of oxygenation is particularly important during treatment. High flow nasal cannula (HFNC) oxygen therapy is a non-invasive respiratory aid that is widely used in the clinic that improves oxygenation state, reduces dead space ventilation and breathing effort, protects the loss of cilia in the airways, and improves patient comfort. AIM: To compare HFNC and non-invasive positive pressure ventilation in the treatment of patients with AECOPD. METHODS: Eighty AECOPD patients were included in the study. The patients were in the intensive care department of our hospital from October 2019 to October 2021. The patients were divided into the control and treatment groups according to the different treatment methods with 40 patients in each group. Differences in patient comfort, blood gas analysis and infection indices were analyzed between the two groups. RESULTS: After treatment, symptoms including nasal, throat and chest discomfort were significantly lower in the treatment group compared to the control group on the 3rd and 5th days (P < 0.05). Before treatment, the PaO2, PaO2/FiO2, PaCO2, and SaO2 in the two groups of patients were not significantly different (P > 0.05). After treatment, the same indicators were significantly improved in both patient groups but had improved more in the treatment group compared to the control group (P < 0.05). After treatment, the white blood cell count, and the levels of C-reactive protein and calcitonin in patients in the treatment group were significantly higher compared to patients in the control group (P < 0.05). CONCLUSION: HFNC treatment can improve the ventilation of AECOPD patients whilst also improving patient comfort, and reducing complications. HFNC is a clinically valuable technique for the treatment of AECOPD.

Novel beagle model of gastric local fibrotic target lesions for the evaluation and training of endoscopic techniques.

BACKGROUND: Novel endoscopic techniques used in the treatment of gastric lesions with local submucosal fibrosis need preclinical evaluation and training due to safety limitations. Therefore, the purpose of our study was to establish an animal model of gastric local fibrotic target lesions and assess its feasibility in the evaluation and training of endoscopic techniques. METHODS: In six experimental beagles, a 50% glucose solution was injected into three submucosal areas of the fundus, body, and antrum of the stomach to create gastric local fibrotic target lesions (experimental group). On post-injection day (PID) 7, the injection sites were assessed endoscopically to confirm the presence of submucosal fibrosis formation, and the dental floss clip traction assisted endoscopic submucosal dissection (DFC-ESD) procedure was performed on the gastric local fibrotic target lesions to confirm its feasibility after endoscopic observation. The normal gastric mucosa of six control beagles underwent the same procedure (control group). All the resected specimens were evaluated by histological examination. RESULTS: All 12 beagles survived without postoperative adverse events. On PID 7, 16 ulcer changes were observed at the injection sites (16/18) under the endoscope, and endoscopic ultrasonography confirmed the local submucosal fibrosis formation in all ulcer lesions. The subsequent DFC-ESD was successfully performed on the 32 gastric target lesions, and the mean submucosal dissection time in the ulcer lesions was greater than that in the normal gastric mucosa (15.3 ± 5.6 vs. 6.8 ± 0.8 min; P < 0.001). There was no difference in rates of en bloc resection, severe hemorrhage, or perforation between the two groups. Histological analysis of the ulcer lesions showed the absence of epithelial or muscularis mucosae and extensive submucosal fibrous tissue proliferations compared with normal gastric mucosa. Overall, endoscopists had high satisfaction with the realism and feasibility of the animal model. CONCLUSION: We developed a novel animal model of gastric local fibrotic target lesions to simulate difficult clinical situations, which strongly appeared to be suitable for the preclinical evaluation and learning of advanced endoscopic techniques.

New insights into the oscillations of the nucleon electromagnetic form factors.

The electromagnetic form factors of the proton and the neutron in the timelike region are investigated. Electron-positron annihilation into antinucleon-nucleon (N¯N) pairs is treated in distorted wave Born approximation, including the final-state interaction in the N¯N system. The latter is obtained by a Lippmann-Schwinger equation for N¯N potentials derived within SU(3) chiral effective field theory. By fitting to the phase shifts and (differential) cross section data, a high quality description is achieved. With these amplitudes, the oscillations of the electromagnetic form factors of the proton and the neutron are studied. It is found that each of them can be described by two fractional oscillators. One is characterized as "overdamped" and dominates near the threshold, while the other is "underdamped" and plays an important role in the high-energy region. These two oscillators are essential to understand the distributions of polarized electric charges induced by hard photons for the nucleons.

[Postoperative Delirium in Patients on Cardiopulmonary Bypass for Cardiovascular Surgeries: Incidence and Influencing Factors].

Objective: To investigate the incidence and influencing factors of postoperative delirium (POD) and subsyndromal delirium (SSD) in patients connected to cardiopulmonary bypass during cardiovascular surgeries. Methods: We collected the general data and the data for the perioperative hematological, physiological, and biochemical indicators and the surgical and therapeutic conditions of patients connected to cardiopulmonary bypass during the course of cardiovascular surgeries conducted at a tertiary-care hospital in Hubei province between May 2022 and September 2022. The outcome indicators, including the incidence of POD and SSD, were assessed with the Nursing Delirium Screening Scale (Nu-DESC). Multinomial logistic regression was performed to analyze the influencing factors of patients with different statuses of POD and SSD. Results: Among the 202 patients, the incidence of SSD, SSD progressing to POD, and no POD or SSD (ND) progressing to POD were 13.4%, 6.4%, and 34.2%, respectively. Regression analysis showed that, with ND patients as the controls, the influencing factors for SSD were preoperative blood glucose (odds ratio [ OR]=0.38, 95% confidence interval [ CI]: 0.19-0.76), intraoperative platelet transfusion ( OR=0.37, 95% CI: 0.15-0.92), intraoperative etomidate ( OR=0.93, 95% CI: 0.87-0.98), and postoperative total bilirubin level ( OR=1.04, 95% CI: 1.01-1.07). For the progression of SSD to POD, the influencing factors were age ( OR=1.09, 95% CI: 1.01-1.17), ASA classification of IV and above ( OR=10.72, 95% CI: 1.85-62.08), intraoperative dexmedetomidine ( OR=1.01, 95% CI: 1.003-1.02), and the duration of mechanical ventilation ( OR=1.04, 95% CI: 1.01-1.07). For the progression of ND to POD, the influencing factors were age ( OR=1.06, 95% CI: 1.02-1.10), middle or high school education ( OR=0.35, 95% CI: 0.15-0.83), and the duration of mechanical ventilation ( OR=1.04, 95% CI: 1.01-1.07). Conclusion: Age, education, ASA classification, preoperative blood glucose, intraoperative platelet transfusion, intraoperative etomidate, intraoperative dexmedetomidine, postoperative total bilirubin, and the duration of mechanical ventilation are influencing factors for different statuses of POD and SSD among patients connected to cardiopulmonary bypass when they are undergoing cardiovascular surgeries. The influencing factors vary across groups of patients with different statuses of POD and SSD. Therefore, we should accurately assess the risk factors of patients with different statuses of POD and SSD and carry out corresponding interventions, thereby preventing or reducing the occurrence of POD and SSD, and ultimately promoting enhanced recovery after surgery.

TMEM41A overexpression correlates with poor prognosis and immune alterations in patients with endometrial carcinoma.

BACKGROUND: Expression levels of transmembrane protein 41A (TMEM41A) are related to the progression of malignant tumors. However, the association between TMEM41A expression and endometrial carcinoma (EC) remains unclear. This study aims to identify the roles of TMEM41A expression in the prognosis of patients with EC and its correlation with EC progression. METHODS: The TMEM41A expression and its correlation with the survival of patients with EC were assessed. Cox regression analysis was used to identify the prognostic factors, while nomograms were used to examine the association between the prognostic factors and the survival of patients with EC. Finally, the link between TMEM41A level and immune microenvironment and RNA modifications was investigated in EC. RESULTS: TMEM41A was overexpressed in EC. TMEM41A overexpression could diagnose the EC and evaluate the poor prognosis of patients. Overexpression of TMEM41A was associated with clinical stage, age, weight, histological subtype, tumor grade, and survival status of patients with EC. Clinical stage, age, tumor grade, radiotherapy, and TMEM41A overexpression were factors of poor prognosis in patients with EC. The nomograms revealed the correlation between the TMEM41A level and survival time of patients with EC at 1, 3, and 5 years. Furthermore, TMEM41A overexpression was significantly correlated with the level of the stromal score, immune score, estimate score, NK CD56 bright cells, iDC, NK cells, eosinophils, pDC, T cells, TReg, cytotoxic cells, mast cells, Th17 cells, neutrophils, aDC, NK CD56 dim cells, TFH, Th2 cells, CD8 T cells, macrophages, immune cell markers, and RNA modifications. CONCLUSIONS: TMEM41A is overexpressed in EC tissues and is associated with the prognosis, immune microenvironment, and RNA modification. Our preliminary studies indicate that overexpression of TMEM41A can potentially serve as a biomarker for EC treatment.

ARGLRR: A Sparse Low-Rank Representation Single-Cell RNA-Sequencing Data Clustering Method Combined with a New Graph Regularization.

The development of single-cell transcriptome sequencing technologies has opened new ways to study biological phenomena at the cellular level. A key application of such technologies involves the employment of single-cell RNA sequencing (scRNA-seq) data to identify distinct cell types through clustering, which in turn provides evidence for revealing heterogeneity. Despite the promise of this approach, the inherent characteristics of scRNA-seq data, such as higher noise levels and lower coverage, pose major challenges to existing clustering methods and compromise their accuracy. In this study, we propose a method called Adjusted Random walk Graph regularization Sparse Low-Rank Representation (ARGLRR), a practical sparse subspace clustering method, to identify cell types. The fundamental low-rank representation (LRR) model is concerned with the global structure of data. To address the limited ability of the LRR method to capture local structure, we introduced adjusted random walk graph regularization in its framework. ARGLRR allows for the capture of both local and global structures in scRNA-seq data. Additionally, the imposition of similarity constraints into the LRR framework further improves the ability of the proposed model to estimate cell-to-cell similarity and capture global structural relationships between cells. ARGLRR surpasses other advanced comparison approaches on nine known scRNA-seq data sets judging by the results. In the normalized mutual information and Adjusted Rand Index metrics on the scRNA-seq data sets clustering experiments, ARGLRR outperforms the best-performing comparative method by 6.99% and 5.85%, respectively. In addition, we visualize the result using Uniform Manifold Approximation and Projection. Visualization results show that the usage of ARGLRR enhances the separation of different cell types within the similarity matrix.

Ratiometric fluorescent detection of total phosphates in frozen shrimp samples using catalytic active Zr(IV) modified gold nanoclusters.

Phosphate salts are important food additives in a variety of foods. In this study, the Zr(IV) modified gold nanoclusters (Au NCs) were prepared for ratiometric fluorescent sensing of phosphate additives in seafood samples. Compared with bare Au NCs, the synthesized Zr(IV)/Au NCs showed stronger orange fluorescence at 610 nm. On the other hand, the Zr(IV)/Au NCs retained the phosphatase-like activity of Zr(IV) ions and could catalyze the hydrolysis of fluorescent substrate 4-methylumbelliferyl phosphate to produce blue emission at 450 nm. The addition of phosphate salts could effectively inhibit the catalytic activity of Zr(IV)/Au NCs, resulting the fluorescence decrease at 450 nm. However, the fluorescence at 610 nm almost unchanged upon the addition of phosphates. Based on this finding, the ratiometric detection of phosphates using the fluorescence intensity ratio (I450/I610) was demonstrated. The method has been further applied for sensing total phosphates in frozen shrimp samples with satisfactory results.

Aneuploid subtypes of circulating tumor cells and circulating tumor-derived endothelial cells predict the overall survival of advanced lung cancer.

Objective: This study aimed to detect circulating tumor cells (CTCs) and circulating tumor-derived endothelial cells (CTECs) in patients with advanced lung cancer, for describing the distribution characteristics of CTC and CTEC subtypes, exploring the correlation between CTC/CTEC subtypes and novel prognostic biomarkers. Methods: A total of 52 patients with advanced lung cancer were enrolled in this study. Using the subtraction enrichment-immunofluorescence in situ hybridization (SE-iFISH) system, CTCs and CTECs derived from these patients were identified. Results: Based on cell size, there were 49.3% small and 50.7% large CTCs, and 23.0% small and 77.0% large CTECs. Triploidy, tetraploidy, and multiploidy varied in the small and large CTCs/CTECs. Besides these three aneuploid subtypes, monoploidy was found in the small and large CTECs. Triploid and multiploid small CTCs and tetraploid large CTCs were associated with shorter overall survival (OS) in patients with advanced lung cancer. However, none of the CTECs subtypes showed a significant correlation with patient prognosis. In addition, we found strong positive correlations (P<0.0001) in the four groups including triploid small cell size CTCs and multiploid small cell size CTECs, and multiploid small cell size CTCs and monoploid small cell size CTECs. Furthermore, combined detection of the specific subtypes, including triploid small CTC and monoploid small CTEC, triploid small CTC and triploid small CTEC, and multiploid small CTC and monoploid small CTEC, were associated with poor prognosis in advanced lung cancer. Conclusions: Aneuploid small CTCs are associated with the outcome of patients with advanced lung cancer. In particular, the combined detection of triploid small CTCs and monoploid small CTECs, triploid small CTCs and triploid small CTECs, and multiploid small CTCs and monoploid small CTECs has clinical significance for predicting prognosis in patients with advanced lung cancer.

Construction of an endoplasmic reticulum stress-related signature in lung adenocarcinoma by comprehensive bioinformatics analysis.

BACKGROUND: Lung Adenocarcinoma (LUAD) is a major component of lung cancer. Endoplasmic reticulum stress (ERS) has emerged as a new target for some tumor treatments. METHODS: The expression and clinical data of LUAD samples were downloaded from The Cancer Genome Atlas (TCGA) and The Gene Expression Omnibus (GEO) database, followed by acquiring ERS-related genes (ERSGs) from the GeneCards database. Differentially expressed endoplasmic reticulum stress-related genes (DE-ERSGs) were screened and used to construct a risk model by Cox regression analysis. Kaplan-Meier (K-M) curves and receiver operating characteristic (ROC) curves were plotted to determine the risk validity of the model. Moreover, enrichment analysis of differentially expressed genes (DEGs) between the high- and low- risk groups was conducted to investigate the functions related to the risk model. Furthermore, the differences in ERS status, vascular-related genes, tumor mutation burden (TMB), immunotherapy response, chemotherapy drug sensitivity and other indicators between the high- and low- risk groups were studied. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the mRNA expression levels of prognostic model genes. RESULTS: A total of 81 DE-ERSGs were identified in the TCGA-LUAD dataset, and a risk model, including HSPD1, PCSK9, GRIA1, MAOB, COL1A1, and CAV1, was constructed by Cox regression analysis. K-M and ROC analyses showed that the high-risk group had a low survival, and the Area Under Curve (AUC) of ROC curves of 1-, 3- and 5-years overall survival was all greater than 0.6. In addition, functional enrichment analysis suggested that the risk model was related to collagen and extracellular matrix. Furthermore, differential analysis showed vascular-related genes FLT1, TMB, neoantigen, PD-L1 protein (CD274), Tumor Immune Dysfunction and Exclusion (TIDE), and T cell exclusion score were significantly different between the high- and low-risk groups. Finally, qRT-PCR results showed that the mRNA expression levels of 6 prognostic genes were consistent with the analysis. CONCLUSION: A novel ERS-related risk model, including HSPD1, PCSK9, GRIA1, MAOB, COL1A1, and CAV1, was developed and validated, which provided a theoretical basis and reference value for ERS-related fields in the study and treatment of LUAD.