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.

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.

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.

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.

Novel 3D Printed Device for Dual-Signaling Ratiometric Photoelectrochemical Readout of Biomarker Using λ-Exonuclease-Assisted Recycling Amplification.

A ratiometric photoelectrochemical (PEC) sensing strategy was proposed for monitoring of carcinoembryonic antigen (CEA) based on a homemade 3D printing device with dual-working photoelectrodes (PE1 and PE2), coupling λ-exonuclease (λ-Exo)-assisted recycling amplification with CdS quantum dots. Gold nanoparticles-functionalized ZnO nanorods were utilized as PEC substrate for generating initial photocurrent and immobilizing DNA probe. Upon incubation of target with DNA trigger/CEA aptamer-modified magnetic bead (tri/apt-MB), DNA trigger dissociated from magnetic bead and then hybridized with capture probe (cp) on PE1 or opened hairpin probe (hp) on PE2 to form double-stranded DNA (dsDNA). The exonuclease could recognize and cleave two newly generated dsDNA, leading to the release of trigger. The free trigger strand continued to hybridize with the remaining cp/hp, which were cleaved by λ-Exo, and then trigger was released again and restarted next recycle with the λ-Exo. After digestion of λ-Exo, the number of capture probes on PE1 was reduced, and many short DNA fragments were produced on PE2, thereby resulting in the decreasing CdS QDs on PE1 and the increasing CdS QDs on PE2. As a result, it was observed that the ratio value of photocurrents (PE1/PE2) significantly decreased with the increasing CEA. Under optimum conditions, the sensing method showed a good linear relationship toward CEA within the dynamic range of 0.02-10 ng mL-1 and a detection limit of 6.0 pg mL-1. Moreover, the ratiometric PEC sensor exhibited good reproducibility, satisfying stability, and remarkable anti-interference performance, which suggests its promising application prospect to detect target CEA.

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.

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.

A new visual immunoassay for prostate-specific antigen using near-infrared excited CuxS nanocrystals and imaging on a smartphone.

A photothermal immune-imaging assay was innovatively designed for the visual quantitative detection of cancer biomarkers by coupling CuxS nanocrystals with a portable infrared thermal imager on a smartphone. The rolling circle amplification (RCA) technique was used for the formation of a CuxS nanocrystal concatemer, thus opening up new territories in immunoassay development.

Wet NH3-Triggered NH2-MIL-125(Ti) Structural Switch for Visible Fluorescence Immunoassay Impregnated on Paper.

This work has looked to explore an innovative and powerful visible fluorescence immunoassay method through wet NH3-triggered structural change of NH2-MIL-125(Ti) impregnated on paper for the detection of carcinoembryonic antigen (CEA). Gold nanoparticles heavily functionalized with glutamate dehydrogenase (GDH) and secondary antibody were used for generation of wet NH3 with a sandwiched immunoassay format. Paper-based analytical device (PAD) coated with NH2-MIL-125(Ti) exhibited good visible fluorescence intensity through wet NH3-triggeried structural change with high accuracy and reproducibility. Moreover, NH2-MIL-125(Ti)-based PAD displayed two visual modes of fluorescence color and physical color with the naked eye and allowed the detection of CEA at a concentration as low as 0.041 ng mL-1. Importantly, the PAD-based assay provides promise for use in the mass production of miniaturized devices and opens new opportunities for protein diagnostics and biosecurity.

Plasmonic Enhancement Coupling with Defect-Engineered TiO2-x: A Mode for Sensitive Photoelectrochemical Biosensing.

This work demonstrates that the photoelectric response of defect-engineered TiO2-x modified with Au nanoparticles can be modulated by oxygen vacancy concentration and excitation wavelength. When strongly plasmonic Au nanoparticles are anchored to defect-engineered TiO2-x by DNA hybridization, several times plasmonic enhancement of photocurrent occurs under 585 nm excitation, and it is employed as a novel signaling mode for developing an improved photoelectrochemical sensing platform. This signaling mode combined with exonuclease III-assisted target recycling amplification exhibits excellent analytical performance, which provides a novel photoelectrochemical detection protocol.

Double Photosystems-Based 'Z-Scheme' Photoelectrochemical Sensing Mode for Ultrasensitive Detection of Disease Biomarker Accompanying Three-Dimensional DNA Walker.

A new double photosystems-based 'Z-scheme' photoelectrochemical (PEC) sensing platform is designed for ultrasensitive detection of prostate-specific antigen (PSA) by coupling with a three-dimensional (3D) DNA walker. Two photosystems consist of CdS quantum dots (photosystem I; PS I) and BiVO4 photoactive materials (photosystem II; PS II), whereas gold nanoparticles (AuNPs) photodeposited on high-active {010} facets of BiVO4 are used as the electron mediators to promote electron transfer from conduction band of PS II to valence band of PS I. 3D DNA walker-based amplification strategy is carried out between hairpin DNA1 conjugated onto the AuNP, hairpin DNA2 labeled with CdS quantum dot (QD-H2), and DNA walker complementary with the PSA aptamer modified to a magnetic bead (Apt-MB). Upon addition of target, DNA walker strand is displaced from DNA walker/Apt-MB to open hairpin DNA1 on AuNP@BiVO4. In the presence of QD-H2, DNA walker induces the hybridization of DNA1 with DNA2 on the gold nanoparticles step by step, thereby resulting in the assembly of CdS QDs on the AuNP@BiVO4 to form Z-scheme double photosystems with strong photocurrent. Under optimum conditions, the Z-scheme PEC sensing system exhibits good photocurrent responses toward target PSA within the working range of 0.01-50 ng mL-1 at a low detection limit of 1.5 pg mL-1. Good reproducibility and accuracy are acquired for analysis of target PSA and human serum specimens relative to the commercial PSA ELISA kit. Importantly, our strategy provides a new horizon for photoelectrochemical in vitro diagnostics.

Cu2+-Doped SnO2 Nanograin/Polypyrrole Nanospheres with Synergic Enhanced Properties for Ultrasensitive Room-Temperature H2S Gas Sensing.

The organic-inorganic nanohybrids are emerging as one of the most attractive sensing materials in the area of gas sensors and usually exhibit some advanced properties because of synergetic/complementary effects between organic molecules and inorganic components. This work demonstrates a novel class of organic-inorganic nanohybrids, Cu2+-doped SnO2 nanograin/poly pyrrole nanospheres, for the sensitive room-temperature H2S gas sensing. Doping Cu2+ in SnO2 nanograins remarkably enhances the surface potential barrier by tailoring surface defects. After polymerizing pyrrole surrounded nanograins in aqueous media to form the organic-inorganic nanohybrids, the resulting nanoheterojunctions further improve the sensitivity. Additionally, the nanohybrids-based sensor provides high surface area and abounding reaction sites to accelerate gas diffusion and adsorption as well as the electron transfer. Compare with pristine SnO2 nanograins alone, the sensitivity of using the nanohybrids increases 7 times for the detection of 50-ppm of H2S. The response and recovery rate can increase 27 and 22 times at room temperature, respectively. Significantly, this work provides an attractive material for the real-time monitoring of H2S, whereas the insights into organic-inorganic composite interactions within the sensing mechanism may pave the way for designing functional materials with tailored properties.

High-index {hk0} faceted platinum concave nanocubes with enhanced peroxidase-like activity for an ultrasensitive colorimetric immunoassay of the human prostate-specific antigen.

Developing simple, high-efficiency non-enzyme bioassays is of great importance for modern analytical systems, but remains a significant challenge. One promising route is to utilize highly efficient nanocatalysts with the exposure of active crystal facets. Herein, we for the first time propose a novel colorimetric immunoassay for the ultrasensitive detection of the human prostate-specific antigen (PSA) based on using a unique type of nanolabel - high-index {hk0} faceted platinum concave nanocubes (HIF-Pt-CNCs). The proposed HIF-Pt-CNCs exhibit superior peroxidase-like catalytic activity that is ∼1500- and ∼4-fold higher than that of natural horseradish peroxidase and Pt nanospheres, respectively, and thereby can provide powerful signal amplification by catalyzing the oxidation of peroxidase substrates in the presence of hydrogen peroxide. Using the HIF-Pt-CNC-labelled anti-PSA detection antibody as a signal probe, the immunoassay is carried out in anti-PSA capture antibody-immobilized microplate wells in a sandwich-type detection mode. Under optimal conditions, the developed immunoassay is able to achieve high sensitivity and specificity for PSA detection in a linear range of 20-2000 pg mL-1 and with an ultralow detection limit of 0.8 pg mL-1, which is much lower than that of conventional enzyme-linked immunosorbent assay (ELISA). Moreover, the method is validated for the analysis of 10 PSA clinical serum specimens, and the results agree very well with those obtained by using a commercialized ELISA kit. Therefore, this new, facile and efficient immunoassay is a promising technique with potential applications in medical science research and clinical diagnosis.

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.

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.

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.

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.

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.