Self-Powered Engineering of Cell Membrane Receptors to On-Demand Regulate Cellular Behaviors.

On-demand engineering of cell membrane receptors to nongenetically intervene in cellular behaviors is still a challenge. Herein, a membraneless enzyme biofuel cell-based self-powered biosensor (EBFC-SPB) was developed for autonomously and precisely releasing Zn2+ to initiate DNAzyme-based reprogramming of cell membrane receptors, which further mediates signal transduction to regulate cellular behaviors. The critical component of EBFC-SPB is a hydrogel film on a biocathode which is prepared using a Fe3+-cross-linked alginate hydrogel film loaded with Zn2+ ions. In the working mode in the presence of glucose/O2, the hydrogel is decomposed due to the reduction of Fe3+ to Fe2+, accompanied by rapid release of Zn2+ to specifically activate a Zn2+-responsive DNAzyme nanodevice on the cell surface, leading to the dimerization of homologous or nonhomologous receptors to promote or inhibit cell proliferation and migration. This EBFC-SPB platform provides a powerful "sensing-actuating-treating" tool for chemically regulating cellular behaviors, which holds great promise in precision biomedicine.

Combined oral low-dose cyclophosphamide endocrine therapy may improve clinical response among patients with metastatic breast cancer via Tregs in TLSs.

Despite limited research on refractory and/or endocrine therapy failure in elderly metastatic breast cancer (MBC) patients, a prior study showed that low-dose oral cyclophosphamide (CY) can improve the overall survival rate of MBC patients, possibly through the immunoregulation of regulatory T cells (Tregs). We preliminarily investigated the combination of endocrine therapy (ET) with oral low-dose CY as salvage therapy in elderly patients via peripheral blood regulatory T-cell analyses. In addition, we evaluated the associations of tumor tertiary lymphoid structures (TLSs) with therapeutic outcomes. HR+/HER2- advanced breast cancer patients who received low-dose CY combined with ET or ET only from April 2015 to August 2021 were enrolled in this retrospective study. The primary outcome was the clinical control rate (CCR), and the secondary outcome was progression-free survival (PFS). Circulating T lymphocyte subpopulations represented by Tregs were monitored during treatment by flow cytometry methods. TLSs wereconfirmed by hematoxylin-eosin staining of pretreatment specimens, and CD3, CD4, and Foxp3 were detected using Opal multicolor immunofluorescence. A total of 85 patients who received CY + ET and 50 patients who received ET only were enrolled, the percentage of patients who received CCR was 73% (62/85) vs. 70% (45/50), and the objective response rate (ORR) was 28% (24/85) vs. 24% (12/50). No deaths occurred during the study period. The mean PFS time was 13 vs. 11 months (P = 0.03). In the CY + ET group, decreases in CD4+/CD25+/Foxp3+ T cells (P < 0.001) were favorable for both clinical control and prolonged PFS (P < 0.001). Compared with patients without TLSs, those with TLSs were more likely to have better clinical control and PFS (mean time = 6 months), and a greater number of Treg cells during TLS pretreatment correlated with longer PFS (P = 0.043). Oral low-dose CY combined with standard ET exerts immunological effects by decreasing Treg levels to achieve improved clinical responses. Moreover, patients with TLSs might benefit more from such therapy than those without TLSs, and a high Treg cell count in TLSs before treatment predicts better therapeutic efficacy.

NIR-driven photoelectrochemical-fluorescent dual-mode biosensor based on bipedal DNA walker for ultrasensitive detection of microRNA.

Optical biosensors have become powerful tools for bioanalysis, but most of them are limited by optic damage, autofluorescence, as well as poor penetration ability of ultraviolet (UV) and visible (Vis) light. Herein, a near-infrared light (NIR)-driven photoelectrochemical (PEC)-fluorescence (FL) dual-mode biosensor has been proposed for ultrasensitive detection of microRNA (miRNA) based on bipedal DNA walker with cascade amplification. Fueled by toehold-mediated strand displacement (TMSD), the bipedal DNA walker triggered by target miRNA-21 is formed through catalytic hairpin assembly (CHA), which can efficiently move along DNA tracks on CdS nanoparticles (CdS NPs)-modified fluorine doped tin oxide (FTO) electrode, resulting in the introduction of upconversion nanoparticles (UCNPs) on electrode surface. Under 980 nm laser irradiation, the UCNPs serve as the energy donor to emit UV/Vis light and excite CdS NPs to generate photocurrent for PEC detection, while the upconversion luminescence (UCL) at 803 nm is monitored for FL detection. This PEC-FL dual-mode biosensor has achieved the ultrasensitive and accurate analysis of miRNA-21 in human serum and different gynecological cancer cells. Overall, the proposed dual-mode biosensor can not only couple the inherent features of each single-mode biosensor but also provide mutual authentication of testing results, which opens up a new avenue for early diagnosis of miRNA-related diseases in clinic.

Pyroelectric-Effect-Assisted Near-Infrared-Driven Photoelectrochemical Biosensor Based on Exponential DNA Amplifier for MicroRNA Detection.

Although near-infrared responsive photoelectrochemical (PEC) biosensors have less damage to biological components compared to UV-visible light, they still reveal an inferior response due to the rapid recombination of photogenerated electron-hole. In this study, a near-infrared-driven PEC biosensor is fabricated for microRNA (miRNA) detection via integrating photoelectricity and pyroelectricity. Upon the introduction of target miRNA-21, the exponential DNA amplifier is triggered based on enzyme-assisted strand displacement amplification (SDA), releasing multiple Ag2S reporter probes to hybridize with capture probes immobilized on a CdS-2-mercaptobenzimidazole (2MBI)-modified photoelectrode. As a result, under the stimulation of NIR, the photoelectric conversion of Ag2S NPs generates the photocurrents. In addition, due to the strong hole acceptor ability of MBI, the pyroelectric effect of CdS-2MBI nanocomposites is enhanced, which generates highly pyroelectro-induced charge separation efficiency and induces the pyroelectric current benefited from the spontaneous polarization of CdS-2MBI caused by the temperature variation under the function of Ag2S nanoheaters. Impressively, this PEC biosensor has achieved the sensitive and selective determination of miRNA-21 with a detection limit as low as 54 fM. Overall, this NIR-driven PEC biosensor based on pyroelectric and photoelectric effects opens up a new horizon for bioanalysis and early disease diagnosis.

Safety, tolerability, pharmacokinetics and immunogenicity of an antibody-drug conjugate (SHR-A1201) in patients with HER2-positive advanced breast cancer: an open, phase I dose-escalation study.

SHR-A1201 is an antibody-drug conjugate (ADC) that combines trastuzumab with DM1 (a chemotherapeutic agent) using a chemical connector. This phase I study investigated the safety, tolerability and pharmacokinetics of SHR-A1201 in patients with human epidermal growth factor receptor 2-positive advanced breast cancer. This phase I study enrolled patients in a traditional 3 + 3 dose-escalation design to receive a single dose of SHR-A1201 (1.2 mg/kg, 2.4 mg/kg, 3.6 mg/kg or 4.8 mg/kg). The observation period of dose-limiting toxicity (DLT) was 21 days. A total of 12 patients were enrolled and received SHR-A1201. Most treatment-emergent adverse events (TEAEs) were grade 1 or 2 in severity, with elevated aspartate aminotransferase (75%), thrombocytopenia (75%), and nausea (66.7%) being reported most frequently. The common grade 3 TEAEs were thrombocytopenia and decreased lymphocyte count, and there were no grade 4 or above TEAEs. There were no serious adverse events or drug-related deaths. One DLT occurred in one patient treated with SHR-A1201 4.8 mg/kg (asymptomatic grade 3 increased γ-glutamyltransferase). The maximum tolerated dose of SHR-A1201 was not lower than that of T-DM1 (3.6 mg/kg). A total of 8.3% (1/12) of patients had ADA-positive reactions 504 h after administration, but no differences were observed in the type, incidence, or severity of TEAEs between patients with and without ADA. SHR-A1201 exhibited the pharmacokinetics characteristics of typical ADCs. An encouraging antitumor effect was observed in the 4.8 mg/kg dose group. SHR-A1201 was well tolerated and safe in patients with advanced HER2-positive breast cancer. The pharmacokinetics parameters showed a linear trend, and the immunogenicity results met the clinical expectations.

Effect of Modified Magnesium Oxide on the Properties of Magnesium Phosphate Cement under a Negative Temperature Environment.

As a rapid repair material, magnesium phosphate cement (MPC) can be used under various environmental temperature conditions, but different temperatures significantly impact its strength and working performance. In this study, based on the surface modification of magnesium oxide, the working and mechanical properties of samples were investigated at an ambient temperature of -5 °C, and the hydration properties and microstructure of MPC were investigated using X-ray diffraction (XRD), thermogravimetric analysis (TG), mercury-in-pressure (MIP), and scanning electron microscopy (SEM). The results show that the modified magnesium oxide at a negative temperature prolongs the setting time of MPC from 10 min to more than 30 min, and fluidity can still be maintained or increased after half an hour. From 1 d to 28 d, the compressive strength growth rate of the reference group was 257.0% compared to 723.8% for the 10 wt% water-glass-modified MgO sample. K-struvite transformed from a blocky growth to a needle-like growth with the modified sample filling the pores and cracks inside the matrix. Compared with the unmodified sample, MPC's porosity decreased from 9.62% to 9.23% for 10 wt% water-glass-modified MgO. Therefore, the surface modification of magnesium oxide not only prolonged the setting time but also further benefited mechanical performance, which provides the prerequisites for MPC construction in negative-temperature environments.

Biometric Photoelectrochemical-Visual Multimodal Biosensor Based on 3D Hollow HCdS@Au Nanospheres Coupled with Target-Induced Ion Exchange Reaction for Antigen Detection.

Three-dimensional (3D) hollow photoactive nanomaterials can enhance light capture due to the light scattering benefiting from the unique hollow nanostructures, which contributes to the decrease in energy loss and the electron-hole recombination during the process of photoelectric conversion. Herein, a 3D hollow HCdS@Au nanosphere synthesized by the templated-assisted method and photodeposition is employed to construct a multimodal sensing platform by combining the photoelectrochemical (PEC) biosensor with colorimetric analysis and photothermal imaging. In the presence of target carcinoembryonic antigen (CEA), a sandwich structure is formed on magnetic beads based on the dual-aptamer recognition, followed by the initiation of rolling circle amplification (RCA) to bind numerous CuO-DNA probes. Upon stimulation by chlorhydric acidic, a large number of Cu2+ is released from CuO, which could interact with yellow HCdS@Au on electrode to produce dark CuS by ion exchange. As a result, with increased CEA level, the photocurrent is weakened and the color of electrode interface is changed from yellow to dark, which thus facilitates the PEC and colorimetric detection of CEA. Simultaneously, the formed CuS with highly photothermal effect can achieve qualitative visual analysis of CEA using a portable infrared thermal imager. This work exhibits an excellent performance for sensitive and selective detection of CEA in the dynamic working range from 0.015 to 2.4 ng/mL with a detection limit as low as 3.5 pg/mL. Moreover, the proposed PEC biosensor is successfully applied to CEA determination in human serum, which holds great promise in accurate analysis of biomarkers and early diagnosis of diseases in the clinic.

Metal-organic framework nanoreactor-based electrochemical biosensor coupled with three-dimensional DNA walker for label-free detection of microRNA.

MicroRNAs (miRNAs), serving as the regulators for gene expression and cellular function, have emerged as the important biomarkers for diagnosis of cancers. In this study, a label-free electrochemical biosensing platform equipped with metal-organic frameworks (MOFs)-based nanoreactors has been developed by coupling three-dimensional (3D) DNA walker for amplification detection of miRNA. The MOF-based nanoreactors are constructed via the encapsulation of GOx in zeolitic imidazolate framework-8 (ZIF-8) driven by the rapid GOx-triggered nucleation of ZIF-8 with high catalytic activity, which also contributes to preserve the biological activity of GOx even in harsh environments. The gold nanoparticles (AuNPs) are further loaded on the surface of ZIF-8 by electrostatic adsorption, which can be used to not only anchor the orbit of 3D DNA walker by Au-S covalent bond but also promote the electron transfer on electrode interface. In the presence of target miRNA-21, the 3D DNA walker is initiated, resulting in the recycling of targets and the immobilization of numerous fuel DNAs with G-quadruplex/hemin complex on the nanoreactors spontaneously. As a result, a cascade catalysis reaction is triggered in the confined space of ZIF-8 nanoreactors, where the H2O2 as an intermediate is generated with the oxidization of glucose catalyzed by GOx and subsequently decomposed by G-quadruplex/hemin HRP-mimicking DNAzyme for the further oxidation of ABTS to obtain a differential pulse voltammetry (DPV) signal. Under the optimal conditions, the proposed electrochemical biosensor exhibits an excellent performance for amplification detection of miRNA-21 in the dynamic working range from 0.1 nM to 10 µM with a detection limit of 29 pM, which opens a new way for clinical analysis of miRNAs and early diagnosis of cancers.

A multicenter randomized trials to compare the bioequivalence and safety of a generic doxorubicin hydrochloride liposome injection with Caelyx ® in advanced breast cancer.

Purpose: To compare the pharmacokinetic (PK) bioequivalence (BE) and safety of a generic pegylated liposomal doxorubicin (PLD) formulation with the reference product Caelyx®. Methods: A multicenter, single-dose, open-label, randomized, two-way crossover study was conducted in patients with breast cancer. For each period, the patients were administered with the test or the reference PLD intravenously at a dose of 50 mg/m2. Cmax, AUC0-t and AUC0-∞ for free, and encapsulated doxorubicin (doxorubicin) and partial AUC (AUC0-48h, AUC48h-t) for encapsulated doxorubicin were evaluated in 17 blood samples taken predose, and increasing time intervals over the following 14 days in each period. A washout period of 28-35 days was observed before crossing over. Results: 48 patients were enrolled and randomised, of which 44 were included and analysed in bioequivalence set (BES). The 90% confidence intervals (CIs) of the geometric mean ratio (GMR) of Cmax, AUC0-t and AUC0-∞ for free doxorubicin and encapsulated doxorubicin all fall within the bioequivalent range of 80% to 125%. The 90% CIs of GMR of partial AUC (AUC0-48h, AUC48h-t) for encapsulated doxorubicin also fall within the bioequivalent range. 48 patients were all included in the safety set (SS). The incidence of treatment-emergent adverse events (TEAEs) related to T and R was 95.8% (46/48) and 97.8% (45/46) respectively. The highest incidence of TEAEs was various laboratory abnormalities. 2 patients withdrew due to T-drug-related AEs. Only one patient experienced serious adverse events and no death occurred in this study. There were no significant differences between the safety profiles of the generic formulation and Caelyx®. Conclusions: Bioequivalence between the test and the reference products was established for free and encapsulated doxorubicin. Clinical trial registration: http://www.chinadrugtrials.org.cn, identifier [CTR20210375].

Effect of Waste Glass on the Properties and Microstructure of Magnesium Potassium Phosphate Cement.

Waste glass is a bulk solid waste, and its utilization is of great consequence for environmental protection; the application of waste glass to magnesium phosphate cement can also play a prominent role in its recycling. The purpose of this study is to evaluate the effect of glass powder (GP) on the mechanical and working properties of magnesium potassium phosphate cement (MKPC). Moreover, a 40mm × 40mm × 40mm mold was used in this experiment, the workability, setting time, strength, hydration heat release, porosity, and microstructure of the specimens were evaluated. The results indicated that the addition of glass powder prolonged the setting time of MKPC, reduced the workability of the matrix, and effectively lowered the hydration heat of the MKPC. Compared to an M/P ratio (MgO/KH2PO4 mass ratio) of 1:1, the workability of the MKPC with M/P ratios of 2:1 and 3:1 was reduced by 1% and 2.1%, respectively, and the peak hydration temperatures were reduced by 0.5% and 14.6%, respectively. The compressive strength of MKPC increased with an increase in the glass powder content at the M/P ratio of 1:1, and the addition of glass powder reduced the porosity of the matrix, effectively increased the yield of struvite-K, and affected the morphology of the hydration products. With an increase in the M/P ratio, the struvite-K content decreased, many tiny pores were more prevalent on the surface of the matrix, and the bonding integrity between the MKPC was weakened, thereby reducing the compressive strength of the matrix. At less than 40 wt.% glass powder content, the performance of MKPC improved at an M/P ratio of 1:1. In general, the addition of glass powders improved the mechanical properties of MKPC and reduced the heat of hydration.

Effect of Cr (III) on hydration, microstructure of magnesium phosphate cement, and leaching toxicity evaluation.

The pollution caused by chromium and its compounds has caused severe harm to the environment, and waste stabilization/solidification containing these contaminants by magnesium phosphate cement (MPC) is one of the best ways to address this problem. If the mechanism between Cr3+ and MPC can be understood, it will significantly improve the latter's solidification performance with respect to ameliorating Cr pollution. In this paper, the compressive strength, microstructure, pH in the process of sample hydration, and leaching toxicity of solidified forms were studied by adding various amounts of Cr3+ into MPC. The setting time of MPC decreased at first and then increased as the Cr3+ concentration increased. The added Cr3+ reacted with the phosphate ions to form mineral phases, which changed the MPC matrix structure. The matrix's compressive strength was higher when the M/P ratio (MgO/KH2PO4 mass ratio) was smaller. When the concentration of Cr3+ was constant, and the M/P ratio was low (< 4:1), the matrix's compressive strength increased as the M/P ratio increased. The presence of Cr3+ changed the system's pH and affected the hydration products' morphology; this trend strengthened as the Cr3+ concentration increased. The highest leaching concentration of Cr3+ was 0.255 mg/L, and the concentration decreased as the M/P ratio decreased. During solidification, the appropriate proportion of MPC can be selected according to the concentration of Cr3+ to achieve better solidification performance.

Baicalin ameliorates atherosclerosis by inhibiting NLRP3 inflammasome in apolipoprotein E-deficient mice.

BACKGROUND: NLR family pyrin domain containing 3 (NLRP3) inflammasome has been implicated in the development of atherosclerosis and several studies have suggested that inhibiting NLRP3 inflammasome could be a potential therapeutic approach to treat atherosclerosis. Baicalin is a flavone glycoside with anti-inflammation, anti-oxidative activities. The inhibition of NLRP3 inflammasome activation by baicalin has also been described. Therefore, the effects of baicalin on NLRP3 inflammasome activation and atherosclerosis were evaluated in present study. METHODS: We established the apolipoprotein E-deficient atherosclerosis mice model. After baicalin treatment, the IL-1, IL-18, and reactive oxygen species (ROS) production, and the plaque area was monitored. We also measured the NLRP3, ASC, caspase-1, ICAM-1, and VCAM-1 expression in atherosclerosis mice after baicalin treatment. We silenced NLRP3 by administration of lentivirus expressing NLRP3 shRNA to atherosclerosis mice and monitored the IL-1, IL-18, and ROS production, and NLRP3 inflammasome activation. RESULTS: Baicalin remarkably inhibited the production of IL-1, IL-18, mitochondria ROS, total ROS, ICAM-1, and VCAM-1. Baicalin reduced the expression of NLRP3 inflammasome and suppressed its activation. Baicalin significantly reduced the plaque area. Silencing NLRP3 resulted in decreased production of IL-1, IL-18, mitochondria ROS, total ROS, ICAM-1, and VCAM-1, and inhibition of NLRP3 inflammasome activation. CONCLUSION: Baicalin ameliorated atherosclerosis by inhibiting NLRP3 inflammasome.

Overexpression of CD155 is associated with PD-1 and PD-L1 expression on immune cells, rather than tumor cells in the breast cancer microenvironment.

BACKGROUND: CD155 is an immune checkpoint protein in cancers and interacts with ligands to regulate the immune microenvironment. The expression of CD155 is correlated with the prognosis and pathological features of breast cancer. AIM: To investigate the expression status of CD155 and the association with exhausted CD4+ helper and CD8+ cytotoxic tumor infiltrating lymphocytes (TILs) and PD-L1 in the breast cancer microenvironment. METHODS: One hundred and twenty-six breast cancer patients with invasive ductal breast cancer were consecutively recruited into this study. Immunohistochemistry was used to detect the expression CD155, PD-L1 and PD-1 on tumor-infiltrating immune cells and tumor cells in the microenvironment. RESULTS: The proportion of patients with CD155 expression was higher in triple negative breast cancer (72.7%) than in Luminal A patients (22.2%, P < 0.05). Patients with positive CD155 expression had a higher percentage of CD4+/PD-1+ helper TILs (30%) than patients with negative CD155 expression (21%, P < 0.05). Patients with positive CD155 expression also had higher cell counts of exhausted CD4+ TILs [47 vs 20/high-power fields (HPF)] and unexhausted CD8+ TILs (30 vs 17/HPF) than patients with negative expression (P < 0.05). CD155 expression was correlated with increased PD-L1 expression in immune cells, 0.8% and 0.02% immune cells expressed PD-L1 in patients with positive and negative CD155 expression, respectively (P < 0.05). CONCLUSION: CD155 was related to an inhibitory immune breast cancer microenvironment. CD155 was associated with a high proportion of exhausted CD4+ and unexhausted CD8+ TILs and high PD-L1 expression in immune cells.

Utilization of oil-based mud drilling cuttings wastes from shale gas extraction for cement clinker production.

A large amount of oil-based mud drilling cuttings (OBMDC) are generated during shale gas extraction, which adversely affects the environment. In order to realize the resource utilization of waste, the object of this paper is to study the feasibility of OBMDC to produce cement clinker. The results showed that at relatively low calcination temperature, adding a certain amount of OBMDC can produce cement clinker successfully and reduce fuel consumption. The compressive strength, hydration performance, and physical characteristics of clinker with 0, 3, 6, and 9% OBMDC were investigated by chemical analysis methods, X-ray diffraction, isothermal calorimetry, mercury intrusion, and energy dispersive spectroscopy. The results showed that the formulated cement has good hydration performance and the compressive strength also meets relevant standards. The heavy metal ions leaching test showed that the preparation of cement clinker by a low amount of OBMDC could effectively reduce the toxicity of OBMDC. In general, the preparation of cement clinker by OBMDC can realize the resource utilization of waste, effectively reduce its toxicity, and play a positive role in environmental protection.

Review of esophageal metastasis from breast cancer.

Esophageal metastasis of primary breast cancer is rare, with nearly all the literature on this topic consisting of case report studies. When breast cancer patients complain of progressive dysphagia after a long disease-free interval after breast surgery, they may be treated and misdiagnosed with a second primary. Our aim was to review all the literature concerning esophageal metastasis of breast cancer, for the purpose of improving the awareness in identifying these patients and providing them proper treatment.

Long disease-free survival (48 months) in a breast cancer patient with ovarian and pelvic metastasis-a case report.

Breast cancer is one of the most common malignant tumors in woman. Ovarian and pelvic metastasis in breast cancer are very rare, and the prognosis is often poor. Lacking typical clinical manifestation, misdiagnose is common. We report a case about a middle-aged postmenopausal woman with complaints of finding a left breast mass and irregular vaginal bleeding. Through ultrasound-guided core-needle biopsy of the masses, the patient's final diagnosis was breast cancer with ovarian and pelvic metastasis. The patient received combinations of chemotherapy (intravenous infusion or peritoneal perfusion), radical surgery (gynecological operation and modified radical mastectomy), radiation and endocrine therapy. Forty-eight months follow-up showed that the patient is generally in good condition and had no signs of local recurrence or metastasis. Invasive ductal carcinoma (IDC) of the breast with unilateral ovarian and pelvic metastasis is rare. It is not easy to differentiate from primary ovarian malignant tumor, and the prognosis is generally poor. We chose a combination chemotherapy regimen sensitive to both breast and ovarian tumors for the patient. The therapeutic effect is remarkable. Only a small number of tumor cells were found in pelvic and ovarian tumors. The patient's breast tumors reached pathological complete remission (pCR), which might be the reason for the patient's good prognosis.

ZIF-8-Assisted NaYF4:Yb,Tm@ZnO Converter with Exonuclease III-Powered DNA Walker for Near-Infrared Light Responsive Biosensor.

This work reports a ZIF-8 (ZIF: Zeolitic Imidazolate Framework)-assisted NaYF4:Yb,Tm@ZnO upconverter for the photoelectrochemical (PEC) biosensing of carcinoembryonic antigen (CEA) under near-infrared (NIR) irradiation on a homemade 3D-printed device with DNA walker-based amplification strategy. The composite photosensitive material NaYF4:Yb,Tm@ZnO, as converter to transfer NIR import to photocurrent output, was driven from annealed NaYF4:Yb,Tm@ZIF-8. Yb3+ and Tm3+-codoped NaYF4 (NaYF4:Yb,Tm) converted NIR excitation into UV emission, matching with the absorption of ZnO for in situ excitation to generate the photocurrent. Upon target CEA introduction, the swing arm of DNA walker including the sequence of CEA aptamer carried out the sandwiched bioassembly with CEA capture aptamer on the G-rich anchorage DNA tracks-functionalized magnetic beads. Thereafter, DNA walker was triggered, and the swing arm DNA was captured by the G-rich anchorage DNA according to partly complementary pairing and Exonuclease III (Exo III) consumed anchorage DNA by a burnt-bridge mechanism to go into the next cycle. The released guanine (G) bases from DNA walker enhanced the photocurrent response on a miniature homemade 3D-printed device consisting of the detection cell, dark box, and light platform. Under optimal conditions, NaYF4:Yb,Tm@ZnO-based NIR light-driven PEC biosensor presented high sensitivity and selectivity for CEA sensing with a detection limit of 0.032 ng mL-1. Importantly, our strategy provides a new horizon for the development of NIR-based PEC biosensors in the aspect of developing MOF-derived photoelectric materials, flexible design of a 3D-printed device, and effective signal amplification mode.

Synergistic association of FOXP3+ tumor infiltrating lymphocytes with CCL20 expressions with poor prognosis of primary breast cancer: A retrospective cohort study.

Studies have shown that forkhead/winged helix transcription factor P3 (FOXP3) tumor infiltrating lymphocytes (TILs) are intimately associated with invasion and survival of many invasive tumors. The inflammatory chemokine ligand 20 (CCL20) and its receptor CCR6 were found to be associated with tumor prognosis in some studies. Although increases in FOXP3 TILs infiltration and CCL20 expression have been revealed in several malignancies, their correlation in human breast tumors is as yet unclear.Surgically resected samples from 156 patients with invasive breast cancer (BC) were assessed for the expression of FOXP3 and CCL20 by immunohistochemistry. Correlation between their expressions and the association with clinicopathological characteristics and patient's prognosis were studied. Forty pairs of fresh BC and their nontumor adjacent tissues (NATs) in BC were carried out by real-time quantitative PCR (qRT-PCR) to evaluate the correlation between FOXP3 and CCL20 mRNA expression.CCL20 and FOXP3 TILs mRNA expression in tumor tissue demonstrated a high correlation (rs = 0.359, P < .001) in this cohort of breast cancer patients. Both elevated CCL20 expression and FOXP3 TILs infiltration were significantly correlated with high histological grade, positive human epidermal growth factor receptor-2 (HER2), high Ki67 index, and axillary lymph node metastases. Tumors with concomitant high expressions of both markers had the worst prognosis. Multivariate analysis showed that these 2 markers were independent predictors of overall survival. The patients with axillary lymph node metastases with the concomitant CCL20 high expression and increased FOXP3 TILs infiltration had the worst overall survival (OS) (P < .001), In lymph node-negative breast cancer patients, the status of CCL20 and FOXP3 was not related to OS (P = .22).The results suggest that CCL20 and FOXP3 TILs may have synergistic effects, and their upregulated expressions may lead to immune evasion in breast cancer. Combinatorial immunotherapeutic approaches aiming at blocking CCL20 and depleting FOXP3 might improve therapeutic efficacy in breast cancer patients.

A 3D printing-based portable photoelectrochemical sensing device using a digital multimeter.

A new enzyme-free and portable photoelectrochemical sensing method based on a homemade three-dimensional (3D) printing device was developed for accurate monitoring of a low-abundance cancer biomarker (carcinoembryonic antigen, CEA, was chosen as a model analyte in this work), coupling glucose-encapsulated liposomes with a digital multimeter readout.

H2-Based Electrochemical Biosensor with Pd Nanowires@ZIF-67 Molecular Sieve Bilayered Sensing Interface for Immunoassay.

With the introduction of gas-based contactless electrochemical biosensors lies the prospects of separating the sensing interface from the bioassembly platform, enhancing stability, and exploring signal transduction mechanism, all intimately linking to development of immunoassay. Herein, we report on a H2-based electrochemical biosensor whose signals derived from the chemical signal transduction between a H2 and Pd nanowires@ZIF-67 (ZIF: Zeolitic Imidazolate Frameworks) bilayered sensing interface for immunoassay. Dendritic Pt nanoparticles (DPNs) conjugated on the detection antibody were introduced on the interface of a magnetic microsphere according to an immune sandwich assembly between the antigen and antibody. H2 as a bridge originates from DPNs catalyzing NH3BH3 and links biological signals to electrical signals by reacting with Pd nanowires. Nevertheless, the response of Pd nanowires being extremely effected by O2 in air due to the competitive adsorption on the surface of Pd nanostructures as well as the reaction between chemisorbed O (Pd-O) and adsorbed dihydrogen lead to a decrease in H absorption into PdHx and poor sensing responses under low target concentration. Porous ZIF-67 (window aperture 0.331 nm) as a molecular sieve self-assembling on the surface of the Pd nanowires film could easily permeate H2 (kinetic diameter of 0.289 nm), while interferential O2 (kinetic diameter of 0.346 nm) has difficultly passing through the ZIF-67 layer to contact Pd nanowires and achieves a response of a lower concentration target as well as faster response rate. Under optimal conditions, H2-based electrochemical biosensors exhibit great response toward target alpha-fetoprotein (AFP) within a dynamic working range of 0.1-50 ng mL-1 at a detection limit of 0.04 ng mL-1. Our strategy provides a reusable sensing interface, high specificity, and acceptable accuracy for the immunoassay. In addition, it also expands a promising platform for application as a molecular sieve in electrochemical biosensors.