Identification macrophage signatures in prostate cancer by single-cell sequencing and machine learning.

BACKGROUND: The tumor microenvironment (TME) encompasses a variety of cells that influence immune responses and tumor growth, with tumor-associated macrophages (TAM) being a crucial component of the TME. TAM can guide prostate cancer in different directions in response to various external stimuli. METHODS: First, we downloaded prostate cancer single-cell sequencing data and second-generation sequencing data from multiple public databases. From these data, we identified characteristic genes associated with TAM clusters. We then employed machine learning techniques to select the most accurate TAM gene set and developed a TAM-related risk label for prostate cancer. We analyzed the tumor-relatedness of the TAM-related risk label and different risk groups within the population. Finally, we validated the accuracy of the prognostic label using single-cell sequencing data, qPCR, and WB assays, among other methods. RESULTS: In this study, the TAM_2 cell cluster has been identified as promoting the progression of prostate cancer, possibly representing M2 macrophages. The 9 TAM feature genes selected through ten machine learning methods and demonstrated their effectiveness in predicting the progression of prostate cancer patients. Additionally, we have linked these TAM feature genes to clinical pathological characteristics, allowing us to construct a nomogram. This nomogram provides clinical practitioners with a quantitative tool for assessing the prognosis of prostate cancer patients. CONCLUSION: This study has analyzed the potential relationship between TAM and PCa and established a TAM-related prognostic model. It holds promise as a valuable tool for the management and treatment of PCa patients.

Sandwich-type immunosensor based on COF-LZU1 as the substrate platform and graphene framework supported nanosilver as probe for CA125 detection.

CA125 is a tumor marker which mainly exists in ovarian, the detection for it with high sensitivity is conducive to improve the effectiveness of tumor prevention and control at early state. Multi-layer graphene oxide derivatives from graphene, and has poor conductivity and high stacked properties that limit its further application. Multi-layer reduced graphene oxide frame (MrGOF) was composed of single-layer graphene sheet and exhibited 3D structure with good dispersion, better conductivity and electrochemical properties after multi-layer graphene oxide underwent alkaline peeling and thermally reduction, the modified graphene are easy to load and combine functional groups and metal nanoparticles. Covalent organic frameworks (COFs) presents a stable frame and through covalent bond connection and has porous properties to adsorb biomolecules, which allows the immobilization of antibody molecules by the porosity and improve the sensitivity of the detection in sensing field. Through the adsorption of COFs for antibody and the probe labeled with functional graphene, we constructed a sandwich type immunosensor with the new material COF-LZU1 as the platform to anchor the CA125 first-antibody and MrGOF combined with amino group and loaded with silver nanoparticles (AgNPs) as the probe to detect tumor marker CA125. The linear range of detection was from 0.001 U/mL to 40 U/mL, with the detection limit was calculated to be 0.00023 U/mL (S/N =3). The prepared immunosensor showed a good application ability for real human serum, which can be attributed to the adsorption of COF-LZU1 for the CA125 first-antibody, and ability to deliver electrons and signal amplification of AgNPs anchored on the sheet structure of MrGOF.

A Novel Electrochemical Immunosensor Based on COF-LZU1 as Precursor to Form Heteroatom-Doped Carbon Nanosphere for CA19-9 Detection.

Porous carbon sphere materials have a large variety of applications in several fields due to the large surface area, adaptable porosity, and good conductivity they possess. Obtaining a steady carbon sphere using the green synthesis method remains a significant challenge. In this experiment, covalent organic frameworks (COFs) were used as a precursor and Fe3O4NPs were integrated into the precursor in order to synthesize a porous carbon sphere material using the one-step pyrolysis method. COFs have an ordered porous structure, perpetual porosity, large surface area, and low density and display good environmental tolerance. These properties make them an excellent precursor for synthesizing porous carbon sphere, which maintains good morphology at high temperatures, and it is not involved in the removal of dangerous reagent and small size restrictions during the synthesis process. In addition to the formation of a porous carbon sphere, transition metal carbon material that contains N element can be an active catalyst. The composites exhibit better activity when Fe is doped into carbon materials containing N element than that of other doped transition metals including Mn and Co. In this situation, the integration of Fe3O4NPs and N element in the COF precursor exposed the active sites of the composites and the two substances synergistically improved the electrocatalytic properties, and the composites were named Fe3O4@NPCS. The constructed Fe3O4@NPCS/GCE immunosensor was applied as a means of detecting CA19-9 antigen and presented a wide linear range from 0.00001 to 10 U/mL with a low detection limit of 2.429 µU/mL (S/N = 3). In addition, the prepared immunosensor was utilized for detecting CA19-9 antigen in the real human serum, and the recovery rates were in the range from 95.24% to 106.38%. Therefore, a porous carbon sphere prepared by COFs as a precursor can be applied for the detection of CA19-9 antigen in real samples, which could be an excellent strategy for CA19-9 antigen detection and could potentially promote the development of COF materials in various electrochemical fields.

Dual function metal-organic frameworks based ratiometric electrochemical sensor for detection of doxorubicin.

Cancer is one of the main diseases threatening human health in the world. Doxorubicin (DOX) is a common anti-cancer drug that can be used for chemotherapy to extend a cancer patient's life. It is our common wish that treatment process of cancer is efficient and secure. Therefore, it is of great significance to develop sensitive, rapid and accurate techniques for anti-cancer drug doxorubicin (DOX) detection. Herein, in our work, a ratiometric electrochemical sensor for DOX detection was designed, which based on MB@MWCNTs/UiO-66-NH2 composites. The porous materials UiO-66-NH2 magically shoulder double function in our ratiometric electrochemical strategy, which can reduce the interior error caused by the various complex materials. Specifically, on the one hand, it can be used to catalyze DOX, which can provide a great current signal to be detected, on the other hand, its special property of absorbing molecules was utilized to load materials as internal reference. Consequently, we chose methylene blue (MB) as the substance that can generate an internal reference signal, because it is a specific and stable electroactive substance. Then, we added MWCNTs as a part of the material modified on the ratiometric electrochemical platform to enhance the signal of the target due to its feature of good electrical conductivity. Under the optimized conditions, the ratiometric electrochemical sensor displayed a wide linear detection with the range from 0.1 µM to 75 µM and the limit of detection (LOD) of 0.051 µM. The applicability of this method in the analysis of actual human saliva samples has been confirmed by the results of selectivity, stability, and reproducibility tests, which was prospective in clinical application.

A label-free electrochemical immunosensor for CA125 detection based on CMK-3(Au/Fc@MgAl-LDH)n multilayer nanocomposites modification.

A label-free electrochemical immunosensor was constructed for cancer antigen 125 (CA125) detection based on multiple-enlargement means of layer-by-layer (LBL) assembly of ordered mesoporous carbon (CMK-3), gold nanoparticles (Au NPs) and MgAl layered double hydroxides containing ferrocenecarboxylic acid (Fc@MgAl-LDH). A CMK-3(Au/Fc@MgAl-LDH)n multilaminate nanocomposites was designed using technology of LBL self-assembly among negatively charged Au NPs, positively charged CMK-3 and Fc@MgAl-LDH nanosheets. The CMK-3(Au/Fc@MgAl-LDH)n multilaminate nanocomposites was used as carriers to increase the immobilization of antibody and the number of loading Fc, conductors to strengthen conductivity and enhancers to amplify signal of Fc step-by-step. Besides, this special and excellent way of LBL assembly can immensely amplify the signal of immunosensor and more immobilize the biomolecules, and label-free method is a more simple the measuring way and the procedure. The immunosensor displayed a wider linear range of 0.01 U ml-1-1000 U ml-1 and a lower detection limit of 0.004 U ml-1. Therefore, the sensor can stablely and accurately be applied for CA125 detection in clinical cancer diagnosis.

Biological functions of nuclear-localized insulin receptor (IR) on A549 lung cancer cells.

INTRODUCTION: Under normal physiological conditions, insulin exhibits a series of important biological functions and roles. Recent studies have shown that insulin is also closely related to the occurrence and development of lung cancer. However, until now, the cellular properties of insulin/insulin receptor (IR) on lung cancer have not been fully revealed. MATERIAL AND METHODS: Indirect immunofluorescence, western blot, and other techniques have been used to identify the biological activity of insulin on lung cancer cell lines. RESULTS: The biological activities of insulin are closely related to its cell behaviour. Therefore, we used lung cancer cell lines as a model to explore the cellular behaviour and properties of insulin/IR in the current study, and the results showed that the IR could internalize into lung cancer cells, and it can also transport into the cell nuclei under insulin treatment. Further study showed that nuclear-localized IR could promote the proliferation of lung cancer cells. CONCLUSION: Taken together, this study shows that IR's nuclear localization is closely related to cell proliferation. This work lays the foundation for further research on the relationship between insulin and the occurrence and development of lung cancer.

A simple method for the preparation of a nickel selenide and cobalt selenide mixed catalyst to enhance bifunctional oxygen activity for Zn-air batteries.

Developing a low-cost, simple, and efficient method to prepare excellent bifunctional electrocatalysts toward the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is critical in rechargeable zinc-air batteries. Non-stoichiometric M0.85Se (M = Ni or Co) nanoparticles are synthesized and modified on nitrogen-doped hollow carbon sphere (NHCS). The NHCS loaded Ni0.85Se (Ni0.85Se-NHCS) with rich Ni3+ presents higher OER activity, whereas the NHCS-loaded Co0.85Se (Co0.85Se-NHCS) with abundant Co2+ displays better ORR activity, respectively. When Co0.85Se-NHCS is mixed with Ni0.85Se-NHCS in a mass ratio of 1 : 1, the resulting mixture (Ni0.85Se/Co0.85Se-NHCS-2) shows better ORR and OER dual catalytic functions than a single selenide. Moreover, zinc-air batteries equipped with Ni0.85Se/Co0.85Se-NHCS-2 as the oxygen electrode catalyst exhibit excellent charge and discharge performance as well as improved stability over precious metals. This work has developed a simple and effective method to prepare excellent bifunctional electrocatalysts for ORR and OER, which is beneficial for the practical large-scale application of zinc-air batteries.

Synthesis, characterization and anti-proliferative activity of heterocyclic hypervalent organoantimony compounds.

Three heterocyclic hypervalent organoantimony chlorides RN(CH2C6H4)2SbCl (2a R = t-Bu, 2b R = Cy, 2c R = Ph) and their chalcogenide derivatives [RN(CH2C6H4)2Sb]2O (3a R = t-Bu, 3b R = Cy, 3c R = Ph) were synthesized and characterized by techniques such as (1)H NMR, (13)C NMR, X-ray diffraction, and elemental analysis. It is found that the anti-proliferative activity detected over these compounds can be attributed to the coordination bond between the antimony and nitrogen atoms of these compounds. Moreover, a preliminary study on mechanistic action suggests that the inhibition effect is ascribable to cell cycle arrest and cell apoptosis.

Effect of isoflavone on balloon catheter-induced neointimal hyperplasia in ovariectomised rabbit carotid artery.

BACKGROUND: This study was designed to investigate the effects of phytoestrogen isoflavone on balloon catheter-induced hyperplasia of carotid artery. METHODS: Forty-eight female New Zealand rabbits were randomly divided into four groups: control (balloon-induced carotid artery injury only); ovariectomy control (ovariectomy and carotid artery injury), oestrogen (ovariectomy, carotid artery injury and nilestriol, 5mg/kg daily for 28 days), and isoflavone (ovariectomy, carotid artery injury and isoflavone 120 mg/kg daily for 28 days). The arterial wall thickness was assessed by coloured ultrasonography, and the oestrogen-α and oestrogen-ß receptors in the abdominal aorta were measured by Western blotting. RESULTS: The medial layer thickness in the isoflavone group was less than in the ovariectomy control group (0.28±0.03 vs. 0.35±0.04 mm, p<0.01), and the intimal/medial layer (I/M) ratio is the isoflavone group was also less than in the ovariectomy control group (16.85±3.79 vs. 48.94±8.92, p<0.01). There was no statistically significant difference in the medial layer thickness or I/M ratio between the isoflavone and the oestrogen groups. The optical density of the oestrogen-α receptors in the isoflavone group (0.317±0.002) was less than in the oestrogen (0.633±0.002) or ovariectomy control group (0.590±0.001, p<0.01). The optical density of the oestrogen-ß receptors in the isoflavone group (1.350±0.002) and the ovariectomy control group (1.2033±0.002) was less than in the oestrogen group (1.7699±0.003, p<0.01). CONCLUSIONS: Isoflavone therapy in the ovariectomised rabbit model attenuated balloon catheter-induced intimal and medial layer hyperplasia in the carotid arteries. Down-regulation of the oestrogen-α receptors may be involved in the hyperplasia-preventative effect.

"No feeding tubes for me!

KIE: A 65-year-old competent nursing home patient, suffering from amyotrophic lateral sclerosis and respirator dependent, refuses a nasogastric feeding tube even though she realizes that her refusal will result in death. The nursing staff and the patient's husband support her decision but two of her three children want her life prolonged. Nicholson, Qiu, and Koch and Ulshoefer discuss whether the refusal would be honored in Britain, China, and West Germany respectively. In Britain, this patient would receive palliative care, and both the respirator and the nasogastric tube would be considered extraordinary and not offered. In China, medical technologies are scarce, physicians are divided on treatment refusal, and the family's attitudes would be influenced by the Confucian tradition of filial piety and whether or not the patient was eligible for free care. In West Germany, this case would be legally considered "passive euthanasia" and the patient's refusal would be honored.^ieng