DNA-based nanosized functional ruthenium(II) complex as potential phosphorescent probe to track tumor cells.

Identifying tumor cells can be challenging due to cancer's complex and heterogeneous nature. Here, an efficacious phosphorescent probe that can precisely highlight tumor cells has been created. By combining the ruthenium(II) complex with oligonucleotides, we have developed a nanosized functional ruthenium(II) complex (Ru@DNA) with dimensions ranging from 300 to 500 nm. Our research demonstrates that Ru@DNA can readily traverse biomembranes via ATP-dependent endocytosis without carriers. Notably, the nanosized ruthenium(II) complex exhibits rapid and selective accumulation within tumor cells, possibly attributed to the nanoparticles' enhanced permeation and retention (EPR) effect. Ru@DNA can also effectively discern and label the transplanted cancer cells in the zebrafish model. Moreover, Ru@DNA is efficiently absorbed into the intestine and further distributed in the pancreas. Our findings underscore the potential of Ru@DNA as a DNA-based nanodevice derived from a functional ruthenium(II) complex. This innovative nanodevice holds promise as an efficient phosphorescent probe for both in vitro and in vivo imaging of living tumor cells.

Risk Factors of Distant Metastatic Parathyroid Carcinoma and Insights into Therapeutic Perspectives.

BACKGROUND: Distant metastatic parathyroid carcinoma (DM-PC) is a rare but often lethal entity with limited data about prognostic indicators. We sought to investigate the risk factors, patterns, and outcomes of DM-PC. METHODS: In this observational cohort study, 126 patients who underwent surgery for PC at a tertiary referral center from 2010 to 2023 were enrolled, among whom 38 had DMs. Univariate and multivariate Cox regression analyses were used to assess the effects of prognostic factors on DM. RESULTS: The cumulative incidence of DM was 14.1%, 33.8%, and 66.9% at 5, 10, and 20 years in the duration of disease course, respectively. DM-PC patients suffered a worse 5-year overall survival of 37.1% compared with 89.8% in the non-DM patients (p < 0.001). DM-PC patients also suffered more previous operations (p < 0.001), higher preoperative serum calcium (p<0.001) and parathyroid hormone (PTH) levels (p < 0.001), lower frequencies of R0 resection (p < 0.001), higher rates of pathological vascular invasion (p = 0.020), thyroid infiltration (p = 0.027), extraglandular extension (p = 0.001), upper aerodigestive tract (UAT) invasion (p < 0.001), and lymph node metastasis (p < 0.001). Multivariate Cox regression revealed that non-R0 resection (HR 6.144, 95% CI 2.881-13.106, p < 0.001), UAT invasion (HR 3.718, 95% CI 1.782-7.756, p < 0.001), and higher preoperative PTH levels (HR 1.001, 95% CI 1.000-1.001, p = 0.012) were independent risk factors of DM. CONCLUSIONS: Upper aerodigestive tract invasion and higher preoperative PTH levels might be risk factors for possible metastatic involvement of PC. R0 resection and closer surveillance should be considered in such cases to minimize the risk of DM and to optimize patient care.

Detection and identification of circulating tumor cells in parathyroid tumors and correlation analysis with clinicopathological features.

INTRODUCTION: The differential diagnosis of parathyroid carcinoma (PC)/parathyroid adenoma (PA) in parathyroid tumors is critical for their management and prognosis. Circulating tumor cells (CTCs) identification in the peripheral blood of parathyroid tumors remains unknown. In this study, we proposed to investigate the differences of CTCs in PC/PA and the relationship with clinicopathologic features to assess its relevance to PC and value in identifying PC/PA. METHODS AND MATERIALS: Peripheral blood was collected from 27 patients with PC and 37 patients with PA treated in our hospital, and the number of chromosome 8 aberrant CTCs was detected by negative magnetic bead sorting fluorescence in situ hybridization (NE-FISH). The differences of CTCs in PC/PA peripheral blood were compared and their diagnostic efficacy was evaluated, and the correlation between CTCs and clinicopathological features of PC was further explored. RESULTS: CTCs differed significantly in PC/PA (p = 0.0008) and were up-regulated in PC, with good diagnostic efficacy. CTCs combined with alkaline phosphatase (ALP) assay improved the diagnostic efficacy in identifying PC/PA (AUC = 0.7838, p = 0.0001). The number of CTCs was correlated with tumor dimensions, but not significantly correlated with clinical markers such as calcium and PTH and pathological features such as vascular invasion, lymph node metastasis and distant metastasis. CONCLUSION: As a non-invasive liquid biopsy method, CTCs test combined with ALP test can be used as an important reference basis for timely and accurate identification and treatment of PC. It is of great significance to improve the current situation of PC diagnosis, treatment and prognosis.

Natural gambogic acid-tuned self-assembly of nanodrugs towards synergistic chemophototherapy against breast cancer.

Gambogic acid (GA) as a naturally derived chemotherapeutic agent is of increasing interest for antitumor therapy. However, current research mainly focuses on improving the pharmacological properties to overcome the shortcomings in clinical applications or as a synergistic anticancer agent in combination with chemotherapy and chemophototherapy. Yet, the material properties of GA (e.g., self-assembly) are often neglected. Herein, we validated the self-assembly function of GA and its huge potential as a single-component active carrier for synergistic delivery using pyropheophorbide-a (PPa) as a drug model. The results showed that self-assembled GA drives the formation of nano-GA/PPa mainly through noncovalent interactions such as π-π stacking, hydrophobic interactions, and hydrogen bonding. Additionally, although no significant differences in cytotoxicity were found between the individual in vitro chemotherapy and combined chemophototherapy, the as-prepared nano-GA/PPa exhibits remarkably improved water solubility and multiple favorable therapeutic features, leading to a prominent in vivo photochemotherapy efficiency of 89.3% inhibition rate with reduced hepatotoxicity of GA. This work highlights the potential of self-assembled GA as a drug delivery carrier for synergistic biomedical applications.

Iron-Nickel synergistic catalysis growth of (Fe,Ni)9S8/Ni3S2@N,S codoped carbon bridged nanowires enhanced oxygen evolution reaction performance.

Improving the conductivity of the electrocatalyst itself is essential for enhancing its performance. In this work, N, S-rich 6-thioguanine (TG) is selected as the ligand to synthesize a Fe, Ni bimetallic porous coordination polymer (PCP), which is then derived to fabricate N,S codoped carbon (NSC)-coated (Fe,Ni)9S8/Ni3S2 bridged nanowires. The (Fe,Ni)9S8/Ni3S2@NSC bridged nanowires obtained through bimetallic synergistic catalysis and self-sulfurization processes not only introduced additional electrocatalytic active sites but also significantly enhance the overall conductivity of the catalyst due to the interconnected nanowire structure. The resulting (Fe,Ni)9S8/Ni3S2@NSC demonstrates remarkable oxygen evolution reaction (OER) performance, exhibiting an overpotential as low as 252 mV at a current density of 10 mA cm-2. This work proposes a novel strategy for enhancing the overall conductivity of catalysts by growing bridged nanowires, providing valuable insights and inspiration for the design and preparation of advanced transition metal sulfide electrocatalysts.

Irradiated tumour cell-derived microparticles upregulate MHC-I expression in cancer cells via DNA double-strand break repair pathway.

Radiotherapy (RT) is used for over 50 % of cancer patients and can promote adaptive immunity against tumour antigens. However, the underlying mechanisms remain unclear. Here, we discovered that RT induces the release of irradiated tumour cell-derived microparticles (RT-MPs), which significantly upregulate MHC-I expression on the membranes of non-irradiated cells, enhancing the recognition and killing of these cells by T cells. Mechanistically, RT-MPs induce DNA double-strand breaks (DSB) in tumour cells, activating the ATM/ATR/CHK1-mediated DNA repair signalling pathway, and upregulating MHC-I expression. Inhibition of ATM/ATR/CHK1 reversed RT-MP-induced upregulation of MHC-I. Furthermore, phosphorylation of STAT1/3 following the activation of ATM/ATR/CHK1 is indispensable for the DSB-dependent upregulation of MHC-I. Therefore, our findings reveal the role of RT-MP-induced DSBs and the subsequent DNA repair signalling pathway in MHC-I expression and provide mechanistic insights into the regulation of MHC-I expression after DSBs.

Induction of therapeutic immunity and cancer eradication through biofunctionalized liposome-like nanovesicles derived from irradiated-cancer cells.

Immunotherapy has revolutionized the treatment of cancer. However, its efficacy remains to be optimized. There are at least two major challenges in effectively eradicating cancer cells by immunotherapy. Firstly, cancer cells evade immune cell killing by down-regulating cell surface immune sensors. Secondly, immune cell dysfunction impairs their ability to execute anti-cancer functions. Radiotherapy, one of the cornerstones of cancer treatment, has the potential to enhance the immunogenicity of cancer cells and trigger an anti-tumor immune response. Inspired by this, we fabricate biofunctionalized liposome-like nanovesicles (BLNs) by exposing irradiated-cancer cells to ethanol, of which ethanol serves as a surfactant, inducing cancer cells pyroptosis-like cell death and facilitating nanovesicles shedding from cancer cell membrane. These BLNs are meticulously designed to disrupt both of the aforementioned mechanisms. On one hand, BLNs up-regulate the expression of calreticulin, an "eat me" signal on the surface of cancer cells, thus promoting macrophage phagocytosis of cancer cells. Additionally, BLNs are able to reprogram M2-like macrophages into an anti-cancer M1-like phenotype. Using a mouse model of malignant pleural effusion (MPE), an advanced-stage and immunotherapy-resistant cancer model, we demonstrate that BLNs significantly increase T cell infiltration and exhibit an ablative effect against MPE. When combined with PD-1 inhibitor (α-PD-1), we achieve a remarkable 63.6% cure rate (7 out of 11) among mice with MPE, while also inducing immunological memory effects. This work therefore introduces a unique strategy for overcoming immunotherapy resistance.

Uridine-Modified Ruthenium(II) Complex as Lysosomal LIMP-2 Targeting Photodynamic Therapy Photosensitizer for the Treatment of Triple-Negative Breast Cancer.

Lysosome-targeted photodynamic therapy, which enhances reactive oxygen species (ROS)-responsive tumor cell death, has emerged as a promising strategy for cancer treatment. Herein, a uridine (dU)-modified Ru(II) complex (RdU) was synthesized by click chemistry. It was found that RdU exhibits impressive photo-induced inhibition against the growth of triple-negative breast cancer (TNBC) cells in normoxic and hypoxic microenvironments through ROS production. It was further revealed that RdU induces ferroptosis of MDA-MB-231 cells under light irradiation (650 nm, 300 mW/cm2). Additional experiments showed that RdU binds to lysosomal integral membrane protein 2 (LIMP-2), which was confirmed by the fact that RdU selectively localizes in the lysosomes of MDA-MB-231 cells and significantly augments the levels of LIMP-2. Molecular docking simulations and an isothermal titration calorimetry assay also showed that RdU has a high affinity to LIMP-2. Finally, in vivo studies in tumor-bearing (MDA-MB-231 cells) nude mice showed that RdU exerts promising photodynamic therapeutic effects on TNBC tumors. In summary, the uridine-modified Ru(II) complex has been developed as a potential LIMP-2 targeting agent for TNBC treatment through enhancing ROS production and promoting ferroptosis.

Severe megaloblastic anemia in a patient with advanced lung adenocarcinoma during treatment with erlotinib: a case report and literature review.

BACKGROUND: Erlotinib is a first-generation, tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR-TKI) used for the treatment patients with NSCLC. Erlotinib is considered as a safe and effective treatment option, with generally good tolerance. Diarrhea and rash are the most common side effects, and more rare side effects appear in long-term real-world applications. Severe erlotinib related megaloblastic anemia is rare and remains unreported. This is the first case report of severe megaloblastic anemia in a patient with advanced lung adenocarcinoma with an EGFR L858R mutation treated with erlotinib. In this report, the clinical manifestations, diagnosis and treatment of erlotinib related severe megaloblastic anemia are described, and the possible pathogenesis and related treatment options are discussed. CASE DESCRIPTION: Herein, we present a 57- year-old non-smoking female diagnosed with metastatic lung adenocarcinoma harboring an EGFR L858R mutation, who had received erlotinib as the first-line therapy. After 44 weeks of treatment, the patient developed severe anemia. Anemia was manifested as megaloblastic anemia with elevated mean corpuscular volume and mean corpuscular hemoglobin. The total vitamin B12 level was below the detection limit of 50.00 pg /mL. Bone marrow smear suggested megaloblastic anemia. Her hematologic parameters were markedly recovered following the withdrawal of erlotinib and vitamin B12 supplement. As a result, the patient was diagnosed with erlotinib-associated megaloblastic anemia. CONCLUSIONS: This is the first case of severe megaloblastic anemia reported with erlotinib. Few of these hematologic adverse effects have been observed in studies on erlotinib, this case report highlights this possibility for long-term erlotinib administration. Close clinical and blood monitoring is recommended for patients receiving long-term TKI therapy.

Facilitating effects of the synergy with zero-valent iron and peroxysulfate on the sludge anaerobic fermentation system: Combined biological enzyme, microbial community and fermentation mechanism assessment.

This study evaluated a synergetic waste activated sludge treatment strategy with environmentally friendly zero-valent iron nanoparticles (Fe0) and peroxysulfate. To verify the feasibility of the synergistic treatment, Fe0, peroxysulfate, and the mixture of peroxysulfate and Fe0 (synergy treatment) were added to different sludge fermentation systems. The study demonstrated that the synergy treatment fermentation system displayed remarkable hydrolysis performance with 435.50 mg COD/L of protein and 197.67 mg COD/L of polysaccharide, which increased 1.13-2.85 times (protein) and 1.12-1.49 times (polysaccharide) for other three fermentation system. Additionally, the synergy treatment fermentation system (754.52 mg COD/L) exhibited a well acidification performance which was 1.35-41.73 times for other systems (18.08-557.27 mg COD/L). The synergy treatment fermentation system had a facilitating effect on the activity of protease, dehydrogenase, and alkaline phosphatase, which guaranteed the transformation of organic matter. Results also indicated that Comamonas, Soehngenia, Pseudomonas, and Fusibacter were enriched in synergy treatment, which was beneficial to produce SCFAs. The activation of Fe0 on peroxysulfate promoting electron transfer, improving the active groups, and increasing the enrichment of functional microorganisms showed the advanced nature of synergy treatment. These results proved the feasibility of synergy treatment with Fe0 and peroxysulfate to enhance waste activated sludge anaerobic fermentation.

Insight into the potentiality of nano zero-valent iron on enhancing the nitrite accumulation and phosphorus removal performance of endogenous partial denitrification systems.

Endogenous partial denitrification (EPD) has drawn a lot of interest due to its abundant nitrite (NO2--N) accumulation capacity. However, the poor phosphate (PO43--P) removal rate of EPD restricts its promotion and application. In this study, the potentiality of various nano zero-valent iron (nZVI) concentrations (0, 20, 40, and 80 mg/L) on NO2--N accumulation and PO43--P removal in EPD systems had been investigated. Results showed that nZVI improved NO2--N accumulation and PO43--P removal, with the greatest nitrate-to-nitrite transformation ratio (NTR) and PO43--P removal rate of 97.74 % and 64.76 % respectively at the optimum nZVI level (80 mg/L). Microbial community analysis also proved that nZVI had a remarkable influence on the microbial community of EPD. Candidatus_Competibacter was contribute to NO2--N accumulation which was enriched from 24.74 % to 40.02 %. The enrichment of Thauera, Rhodobacteraceae, Pseudomonas were contributed to PO43--P removal. The chemistry of nZVI not only compensated for the deficiency of biological PO43--P removal, but also enhanced NO2--N enrichment. Therefore, nZVI had the huge potentiality to improve the operational performance of the EPD system.

Model-Heterogeneous Semi-Supervised Federated Learning for Medical Image Segmentation.

Medical image segmentation is crucial in clinical diagnosis, helping physicians identify and analyze medical conditions. However, this task is often accompanied by challenges like sensitive data, privacy concerns, and expensive annotations. Current research focuses on personalized collaborative training of medical segmentation systems, ignoring that obtaining segmentation annotations is time-consuming and laborious. Achieving a perfect balance between annotation cost and segmentation performance while ensuring local model personalization has become a valuable direction. Therefore, this study introduces a novel Model-Heterogeneous Semi-Supervised Federated (HSSF) Learning framework. It proposes Regularity Condensation and Regularity Fusion to transfer autonomously selective knowledge to ensure the personalization between sites. In addition, to efficiently utilize unlabeled data and reduce the annotation burden, it proposes a Self-Assessment (SA) module and a Reliable Pseudo-Label Generation (RPG) module. The SA module generates self-assessment confidence in real-time based on model performance, and the RPG module generates reliable pseudo-label based on SA confidence. We evaluate our model separately on the Skin Lesion and Polyp Lesion datasets. The results show that our model performs better than other methods characterized by heterogeneity. Moreover, it exhibits highly commendable performance even in homogeneous designs, most notably in region-based metrics. The full range of resources can be readily accessed through the designated repository located at HSSF(github.com) on the platform of GitHub.

AutoEdge-CCP: A novel approach for predicting cancer-associated circRNAs and drugs based on automated edge embedding.

The unique expression patterns of circRNAs linked to the advancement and prognosis of cancer underscore their considerable potential as valuable biomarkers. Repurposing existing drugs for new indications can significantly reduce the cost of cancer treatment. Computational prediction of circRNA-cancer and drug-cancer relationships is crucial for precise cancer therapy. However, prior computational methods fail to analyze the interaction between circRNAs, drugs, and cancer at the systematic level. It is essential to propose a method that uncover more valuable information for achieving cancer-centered multi-association prediction. In this paper, we present a novel computational method, AutoEdge-CCP, to unveil cancer-associated circRNAs and drugs. We abstract the complex relationships between circRNAs, drugs, and cancer into a multi-source heterogeneous network. In this network, each molecule is represented by two types information, one is the intrinsic attribute information of molecular features, and the other is the link information explicitly modeled by autoGNN, which searches information from both intra-layer and inter-layer of message passing neural network. The significant performance on multi-scenario applications and case studies establishes AutoEdge-CCP as a potent and promising association prediction tool.

FBW7/GSK3ß mediated degradation of IGF2BP2 inhibits IGF2BP2-SLC7A5 positive feedback loop and radioresistance in lung cancer.

BACKGROUND: The development of radioresistance seriously hinders the efficacy of radiotherapy in lung cancer. However, the underlying mechanisms by which radioresistance occurs are still incompletely understood. The N6-Methyladenosine (m6A) modification of RNA is involved in cancer progression, but its role in lung cancer radioresistance remains elusive. This study aimed to identify m6A regulators involved in lung cancer radiosensitivity and further explore the underlying mechanisms to identify therapeutic targets to overcome lung cancer radioresistance. METHODS: Bioinformatic mining was used to identify the m6A regulator IGF2BP2 involved in lung cancer radiosensitivity. Transcriptome sequencing was used to explore the downstream factors. Clonogenic survival assays, neutral comet assays, Rad51 foci formation assays, and Annexin V/propidium iodide assays were used to determine the significance of FBW7/IGF2BP2/SLC7A5 axis in lung cancer radioresistance. Chromatin immunoprecipitation (ChIP)-qPCR analyses, RNA immunoprecipitation (RIP) and methylated RNA immunoprecipitation (MeRIP)-qPCR analyses, RNA pull-down analyses, co-immunoprecipitation analyses, and ubiquitination assays were used to determine the feedback loop between IGF2BP2 and SLC7A5 and the regulatory effect of FBW7/GSK3ß on IGF2BP2. Mice models and tissue microarrays were used to verify the effects in vivo. RESULTS: We identified IGF2BP2, an m6A "reader", that is overexpressed in lung cancer and facilitates radioresistance. We showed that inhibition of IGF2BP2 impairs radioresistance in lung cancer both in vitro and in vivo. Furthermore, we found that IGF2BP2 enhances the stability and translation of SLC7A5 mRNA through m6A modification, resulting in enhanced SLC7A5-mediated transport of methionine to produce S-adenosylmethionine. This feeds back upon the IGF2BP2 promoter region by further increasing the trimethyl modification at lysine 4 of histone H3 (H3K4me3) level to upregulate IGF2BP2 expression. We demonstrated that this positive feedback loop between IGF2BP2 and SLC7A5 promotes lung cancer radioresistance through the AKT/mTOR pathway. Moreover, we found that the ubiquitin ligase FBW7 functions with GSK3ß kinase to recognize and degrade IGF2BP2. CONCLUSIONS: Collectively, our study revealed that the m6A "reader" IGF2BP2 promotes lung cancer radioresistance by forming a positive feedback loop with SLC7A5, suggesting that IGF2BP2 may be a potential therapeutic target to control radioresistance in lung cancer.

Intake of dietary flavonoids in relation to bone loss among U.S. adults: a promising strategy for improving bone health.

Dietary flavonoids have been recommended for improving bone health due to their antioxidant, anti-inflammatory and osteogenic properties. However, the effectiveness of each flavonoid subclass in the prevention and treatment of osteoporosis remains controversial. The objective of the current study was to examine the association between the intake of flavonoid subclasses and bone loss in 10 480 U.S. adults in the National Health and Nutrition Examination Survey. We employed a multinomial logistic regression model to calculate the odds ratios (OR) and 95% confidence intervals (95% CI). The intake of flavones, isoflavones, and flavanones was beneficially associated with osteoporosis (ORQ5 vs. Q1 = 0.44; 95% CI: 0.30-0.64 for flavones; ORQ5 vs. Q1 = 0.53; 95% CI: 0.37-0.77 for isoflavones; ORQ5 vs. Q1 = 0.66; 95% CI: 0.45-0.97 for flavanones). A higher intake of flavones and flavanones was significantly associated with a lower risk of bone loss at the femoral neck rather than the lumbar spine. Notably, stratified analysis showed that genistein had a harmful association with osteopenia in the population with lower serum calcium levels, whereas it had a beneficial association with osteoporosis in the population with higher serum calcium levels. Multiple sensitivity analyses were performed to test the robustness of the results, including subgroup analysis, exclusion of individuals' use of anti-osteoporosis, corticosteroid, and estrogenic medications, adjusting more potential confounders and calculation of the E-value. Overall, incorporating this modifiable diet into an individual's lifestyle could provide potential possibilities to prevent and ameliorate osteoporosis.

Transarterial chemoembolization combined donafenib with/without PD-1 for unresectable HCC in a multicenter retrospective study.

Background & aims: This multicenter retrospective study evaluated the efficacy and safety of transarterial chemoembolization (TACE) combined with donafenib and a programmed death-1 (PD-1) inhibitor (TACE+DP) and TACE combined with donafenib (TACE+D) for unresectable hepatocellular carcinoma (uHCC). Methods: The clinical data of 388 patients with uHCC who received TACE+DP or TACE+D as first-line treatment at six Chinese academic centers from July 2021 to July 2022 were collected and analyzed retrospectively. Patients in the TACE+DP group received an intravenous administration of a PD-1 inhibitor every three weeks and oral donafenib (0.2 g) twice daily until intolerable toxicity or disease progression. Patients in the TACE+D group received the same dose of donafenib for 3-5 days after TACE. Overall survival (OS) and progression-free survival (PFS)were analyzed by Kaplan-Meier method and log-rank test. The tumor response was compared between the two groups according to modified RECIST criteria. Adverse events were also analyzed between the two groups. Results: The TACE+D group included 157 patients and the TACE+DP group included 166 patients. Patients in the TACE+DP group had a longer median OS (18.1 vs. 13.2 months, P<0.001) and longer median PFS (10.6 vs. 7.9 months, P<0.001) than those in the TACE+D group. Patients in the TACE+DP group achieved a greater objective response rate (ORR; 50.6% vs. 41.4%, P=0.019) and greater disease control rate (DCR) (89.2% vs. 82.8%, P=0.010) than those in the TACE+D group. No significant differences were found in the incidence or severity of adverse events between the TACE+DP and TACE+D groups (any grade: 92.9% vs. 94.6%, P=0.270; grade 3 or 4: 33.8% vs. 37.3%, P=0.253). Conclusion: With favorable safety and tolerability, TACE combined with donafenib and PD-1 inhibitors significantly improved PFS, OS, and ORR compared to TACE combined with donafenib.

Machine learning-based prediction models for parathyroid carcinoma using pre-surgery cognitive function and clinical features.

Patients with parathyroid carcinoma (PC) are often diagnosed postoperatively, due to incomplete resection during the initial surgery, resulting in poor outcomes. The aim of our study was to investigate the pre-surgery indicators of PC and try to develop a predictive model for PC utilizing machine learning. Evaluation of pre-surgery neuropsychological function and confirmation of pathology were carried out in 133 patients with primary hyperparathyroidism in Beijing Chaoyang Hospital from December 2019 to January 2023. Patients were randomly divided into a training cohort (n = 93) and a validating cohort (n = 40). Analysis of the clinical dataset, two machine learning including the extreme gradient boosting (XGBoost) and the least absolute shrinkage and selection operator (LASSO) regression were utilized to develop the prediction model for PC. Logistic regression analysis was also conducted for comparison. Significant differences in elevated parathyroid hormone and decreased serum phosphorus in PC compared to (BP). The lower score of MMSE and MOCA was observed in PC and a cutoff of MMSE < 24 was the optimal threshold to stratify PC from BP (area under the curve AUC 0.699 vs 0.625). The predicted probability of PC by machine learning was similar to the observed probability in the test set, whereas the logistic model tended to overpredict the possibility of PC. The XGBoost model attained a higher AUC than the logistic algorithms and LASSO models. (0.835 vs 0.683 vs 0.607). Preoperative cognitive function may be a probable predictor for PC. The cognitive function-based prediction model based on the XGBoost algorithm outperformed LASSO and logistic regression, providing valuable preoperative assistance to surgeons in clinical decision-making for patients suspected PC.

Effect comparisons of different conditioners and microbial agents on the degradation of estrogens during dairy manure composting.

To investigate the degradation efficiency of conditioners and commercial microbial agents on estrogens (E1, 17α-E2, 17ß-E2, E3, EE2, and DES) in the composting process of dairy manure, seven different treatments (RHB-BF, OSP-BF, SD-BF, MR-BF, MR-FS, MR-EM, and MR-CK) under forced ventilation conditions were composted and monitored regularly for 30 days. The results indicated that the removal rates of estrogens in seven treatments ranged from 95.35% to 99.63%, meanwhile the degradation effect of the composting process on 17ß-Estradiol equivalent (EEQ) was evaluated, and the removal rate of ΣEEQ ranged from 96.42% to 99.72%. With the combined addition of rice husk biochar (RHB) or oyster shell powder (OSP) and bio-bacterial fertilizer starter cultures (BF), namely RHB-BF and OSP-BF obviously promoted the rapid degradation of estrogens. 17ß-E2 was completely degraded on the fifth day of composting in OSP-BF. Microbial agents have some promotional effect and enhances the microbial degradation of synthetic estrogen (EE2, DES). According to the results of RDA, pH and EC were the main environmental factors affecting on the composition and succession of estrogen-related degrading bacteria in composting system. As predominant estrogens-degrading genera, Acinetobacter, Bacillus, and Pseudomonas effected obviously on the change of estrogens contents. The research results provide a practical reference for effective composting of dairy manure to enhancing estrogens removal and decreasing ecological risk.

Inferring gene regulatory network from single-cell transcriptomes with graph autoencoder model.

The gene regulatory structure of cells involves not only the regulatory relationship between two genes, but also the cooperative associations of multiple genes. However, most gene regulatory network inference methods for single cell only focus on and infer the regulatory relationships of pairs of genes, ignoring the global regulatory structure which is crucial to identify the regulations in the complex biological systems. Here, we proposed a graph-based Deep learning model for Regulatory networks Inference among Genes (DeepRIG) from single-cell RNA-seq data. To learn the global regulatory structure, DeepRIG builds a prior regulatory graph by transforming the gene expression of data into the co-expression mode. Then it utilizes a graph autoencoder model to embed the global regulatory information contained in the graph into gene latent embeddings and to reconstruct the gene regulatory network. Extensive benchmarking results demonstrate that DeepRIG can accurately reconstruct the gene regulatory networks and outperform existing methods on multiple simulated networks and real-cell regulatory networks. Additionally, we applied DeepRIG to the samples of human peripheral blood mononuclear cells and triple-negative breast cancer, and presented that DeepRIG can provide accurate cell-type-specific gene regulatory networks inference and identify novel regulators of progression and inhibition.

Radiated tumor cell-derived microparticles effectively kill stem-like tumor cells by increasing reactive oxygen species.

Stem-like tumor cells (SLTCs) are thought to be the cellular entity responsible for clinical recurrence and subsequent metastasis. Inhibiting or killing SLTCs can effectively reduce recurrence and metastasis, yet little has been done to clear SLTCs because they are usually resistant to chemotherapy, radiotherapy, and even immunotherapy. In this study, we established SLTCs by low-serum culture and confirmed that the low-serum-cultured tumor cells were in a quiescent state and resistant to chemotherapy, showing features of SLTCs, consistent with the reported data. We demonstrated that SLTCs had high levels of reactive oxygen species (ROS). Based on the finding that radiated tumor cell-derived microparticles (RT-MPs) contained ROS, we used RT-MPs to kill SLTCs. We found that RT-MPs could further increase ROS levels and kill SLTCs in vivo and in vitro partially by ROS carried by the RT-MPs themselves, providing a new method for eliminating SLTCs.