Search

Immobilizing ligands is a crucial part of preparing optical sensors and directly connected to the sensitivity, stability, and other characteristics of sensors.

A novel efficacious strategy for real-time monitoring of the release of hydrophobic cargo curcumin (molecule model nutraceuticals) from a lipid-curcumin-loaded silica colloidal crystal (L(Cur)-SCC) film controlled by lipase was developed. Curcumin was dispersed in a proportion of a digestible lipid complex (glycerol trioleate and glycerol tristearate) to prepare a lipid-curcumin complex and then loaded into the SCC film by a capillary to prepare an L(Cur)-SCC film. Lipase-triggered degradation of the digestible lipid complex resulted in curcumin release being tracked in real-time by ordered porous layer interferometry (OPLI). The optical thickness changes (ΔOT) of the L(Cur)-SCC film depend on the mass changes of the lipid-curcumin complex due to the migration of interference fringes caused by the lipase degradation of the digestible lipid complex. Curcumin release from the L(Cur)-SCC film was characterized and analyzed in combination with an ultraviolet-visible spectrophotometer, a nanoparticle size analyzer, and an attenuated total reflection infrared spectrometer. The introduction of a soluble dietary fiber (pectin) into the L(Cur)-SCC film delayed the release rate of curcumin. Furthermore, the real-time sustained release of curcumin from the L(Cur)-SCC film in the simulated digestive fluids was tracked. This study provides an early exploration of the real-time controlled release of lipid-soluble nutraceuticals in the gastrointestinal tract.

Purpose: Near-IR fluorescence imaging has great potential for noninvasive in vivo imaging of tumors. In this study, we show the preferential uptake and retention of two hepatamethine cyanine dyes, IR-783 and MHI-148, in tumor cells and tissues.Experimental Design: IR-783 and MHI-148 were investigated for their ability to accumulate in human cancer cells, tumor xenografts, and spontaneous mouse tumors in transgenic animals. Time- and concentration-dependent dye uptake and retention in normal and cancer cells and tissues were compared, and subcellular localization of the dyes and mechanisms of the dye uptake and retention in tumor cells were evaluated using organelle-specific tracking dyes and bromosulfophthalein, a competitive inhibitor of organic anion transporting peptides. These dyes were used to detect human cancer metastases in a mouse model and differentiate cancer cells from normal cells in blood.Results: These near-IR hepatamethine cyanine dyes were retained in cancer cells but not normal cells, in tumor xenografts, and in spontaneous tumors in transgenic mice. They can be used to detect cancer metastasis and cancer cells in blood with a high degree of sensitivity. The dyes were found to concentrate in the mitochondria and lysosomes of cancer cells, probably through organic anion transporting peptides, because the dye uptake and retention in cancer cells can be blocked completely by bromosulfophthalein. These dyes, when injected to mice, did not cause systemic toxicity.Conclusions: These two heptamethine cyanine dyes are promising imaging agents for human cancers and can be further exploited to improve cancer detection, prognosis, and treatment. Clin Cancer Res; 16(10); 2833–44. ©2010 AACR.

Supplementary Data from Near IR Heptamethine Cyanine Dye–Mediated Cancer Imaging

In order for the colloidal crystal films to be better applied, the influence of relative humidity on the preparation of silica colloidal crystal (SCC) films was systematically studied to solve the problem of different thicknesses of SCC films prepared by different batches under the conditions with the same temperature, concentration of suspension and diameter of the particles. SCC films with 190 nm particles were prepared by static vertical deposition method under different humidity regulated by saturated salt solutions, and the thickness of the films was obtained by an interferometric method. The results showed that the increase in humidity would reduce the thickness of the prepared films, which was believed to be caused by the decrease in evaporation rate after the wetting film absorbs water vapor. A new formula for calculating film thickness was proposed and verified from a series of experiments. With the control of humidity, high-quality SCC films with controlled thickness can be repeatedly prepared.

Different vegetable oils have different nutritional components, especially in terms of the composition of their fatty acids, which can only be reflected after entering the human body. Therefore, when judging their health value and identifying high-quality vegetable oils, in addition to the analysis of their ingredients, tracking their hydrolysis process in the human body is a very important aspect. However, most identification methods or simulated digestion studies fail to achieve this. In this paper, we applied ordered porous layer interferometry (OPLI) for the real-time monitoring of optical thickness changes (ΔOT) to track the hydrolysis process of four kinds of vegetable oil. Further, this study can obtain precise data (the initial rate and degree of hydrolysis) to provide more information on the hydrolysis ability of different vegetable oils and give references for their nutritional and functional evaluation. In addition, it provides more possibilities for the adulteration identification and bioavailability analysis of vegetable oils.

IntroductionMorphological evaluation is used to select embryos for in vitro fertilisation. However, it does not fully reflect the implantation potential. Preimplantation genetic testing for aneuploidies (PGT-A) can detect embryonic aneuploidy, but biopsy procedure is invasive. Currently, a non-invasive PGT (ni-PGT) approach using spent medium is being evaluated. However, the clinical benefit of ni-PGT has not been clearly demonstrated. A multicentre randomised trial is needed to verify whether ni-PGT can be an new effective tool for evaluating embryos.Methods and analysisOverall, 1148 couples aged 35~42 (women) receiving in vitro fertilization–intracytoplasmic sperm injection are planned to be enrolled. Couples will be digitally randomised to (1) ni-PGT and (2) conventional morphology groups at a 1:1 treatment ratio. The primary outcome will be the ongoing pregnancy rate related to the first transfer cycle within 6 months after oocyte retrieval.Ethics and disseminationThe study protocol is approved by the Ethics Committee of Peking University Third Hospital and the participating hospitals. The results will be disseminated through international conferences and scientific journals.Trial registration numberNCT04339166.

Kinetic and affinity analysis of protein interactions reveals information on their related activities in biological processes. Herein, we established a system for evaluating the kinetics and affinity of the interaction between protein A and various IgG species on the surface of silica spheres of silica colloidal crystal (SCC) films by the extraordinary optical interference capabilities of 190 nm silica spheres after self-assembly. The equilibrium association constant (KA) was calculated by the equilibrium Langmuir model and nonlinear least-squares analysis of time-dependent data. The relative protein A/IgG binding affinity is human rabbitcowgoat. In addition, the competitive interaction of distinct species of IgG with protein A at the interface of SCC films was studied and performed. These findings may help with the use of protein A and other recognition components in a number of sensor types. Furthermore, this research might offer a novel approach to determining the kinetics and affinity of proteins on the surface of spheres particles, which may contribute to the development of the application of spheres particles in pharmaceutical science, biomedical engineering, and other techniques.

Accurate discriminating nerve fibers is a prerequisite for right suturing nerves in nerve transfer operation. Various methods have been developed for identification of motor and sensory fibers, but no simple method meets the requirements in clinic. In this study, a surface-enhanced Raman scattering (SERS) lever strategy is designed and developed to detect Acetylcholinesterase (AchE) ultrasensitively, in which using produced thiocholine with weak intrinsic Raman activity (four ounces) to adjust absorbance of Rhodamine B with strong intrinsic Raman activity (thousand catties) on SERS-active substrates is to increase the sensitivity. Employing a miniaturized SERS substrate, SERS-active microneedles, is to decrease the volume of enzymolysis systems. Adopting an internal reference is to increase the repeatability of collected signal. The ultrasensitive AchE detection method discriminate samples with four times of difference in enzyme activity between 1-1 × 10

This study aims to evaluate the effect of blastocyst- and cleavage-stage embryo transfers with different numbers of transferred embryos on pregnancy outcomes in China. This was a retrospective cohort study that collected 24,422 frozen-thawed embryo transfer (FET) cycles in two affiliated hospitals of Peking University Health Science Center between January 2015 and May 2018. They were divided into four groups: the single cleavage-stage embryo transfer group (C-1) (763 cycles), double cleavage-stage embryo transfer group (C-2) (13,004 cycles), single blastocyst-stage embryo transfer group (B-1) (7913 cycles), and double blastocyst-stage embryo transfer group (B-2) (2046 cycles). Of the four groups, the live birth rate was the lowest in the C-1 group (11.8%) while it was the highest in the B-2 group (33.6%). However, the B-2 group was accompanied with higher risks of miscarriages, maternal complications, twin births, preterm births, and low birth weight. Compared with the C-2 group, the B-1 group had a lower live birth rate (23.0 vs 29.0%; aOR, 0.78; 95% CI, 0.72–0.85), but also had a lower risk for twin births (1.9 vs 23.4%; aOR, 0.06; 95% CI, 0.04–0.09) and preterm births (9.6 vs 16.1%; aOR, 0.51; 95% CI, 0.41–0.65). The probability of live birth in the B-1 group declined from 0.25 at 20–29 years old to 0.08 at > 40 years old, while the probabilities of adverse outcomes went up with maternal age. It can be concluded that single-blastocyst embryo transfer seems to be the best choice for all maternal ages. This group of embryo transfer has significantly reduced adverse neonatal outcomes. Especially, women with younger maternal age in this group appear to prominently benefit from single-blastocyst transfer. Electronic supplementary material The online version of this article (10.1007/s43032-020-00247-x) contains supplementary material, which is available to authorized users.

The optimal assisted reproductive treatment strategy for infertile women with unilateral tubal obstruction remains uncertain. To investigate the role of intrauterine insemination (IUI) in the treatment of infertile women with unilateral tubal occlusion, the data of 148 couples were retrospectively collected and analyzed. Seventy-eight infertile women with unilateral occlusion diagnosed by hysterosalpingography (HSG) were categorized as the study group and 70 others with unexplained infertility as the control group. The study group was divided into a proximal occlusion subgroup and a mid-distal occlusion subgroup for further analysis. The main outcomes, namely the clinical pregnancy rate (CPR), ongoing pregnancy rate (OPR), and live birth rate (LBR) per cycle, were analyzed. Our results showed a tendency of lower CPR, OPR, and LBR in the study group than in the control group, without statistical significance. Further investigations revealed that the unilateral proximal occlusion subgroup had similar CPR, OPR, and LBR as the control group, while the unilateral mid-distal occlusion subgroup had significantly lower CPR (5.1% vs. 20.0%, P=0.035), OPR (5.1% vs. 20.0%, P=0.035), and LBR (5.1% vs. 20.0%, P=0.035) than the control group. In conclusion, the clinical outcomes of IUI were worse in patients with unilateral tubal occlusion than in those with unexplained infertility. This might be primarily caused by the worse outcome of patients with unilateral mid-distal tubal occlusion instead of proximal occlusion.

Although tumor-associated macrophages (TAMs) have been shown to promote cancer progression, their roles in tumor development and resistance to therapy remain to be fully understood, mainly because of the lack of a good approach to evaluate the dynamic changes of heterogeneous macrophages in their residing microenvironment. Here, we report an approach of using antibiofouling PEG-b-AGE polymer-coated iron oxide nanoparticles (IONPs) for targeted imaging of mannose receptor (CD206)-expressing M2-like TAMs. Antibiofouling polymer coatings block non-specific phagocytosis of IONPs by different cells but enable ligand-mediated CD206(+) M2-like macrophage targeting after surface functionalizing with mannose (Man-IONP). Costaining tissue sections of the 4T1 mouse mammary tumors using an anti-CD206 antibody and fluorescent dye (TRITC)-labeled Man-IONP showed 94.7 ± 4.5% colocalization of TRITC-Man-IONPs with the anti-CD206 antibody. At 48 h after intravenous (i.v.) injection of Man-IONPs, magnetic resonance imaging of mice bearing orthotopic 4T1 mammary tumors showed a significantly larger IONP-induced decrease of the transverse relaxation time (T(2)) in tumors with 29.4 ± 1.5 ms compared to 12.3 ± 3.6 ms in tumors that received non-targeted IONP probes (P < 0.001). Immunofluorescence-stained tumor tissue sections collected at 6, 18, and 24 h after i.v. administration of the nanoprobes revealed that Man-IONPs specifically targeted CD206(+) M2-like macrophages in various tumor areas at all time points, while nonconjugated IONPs were absent in the tumor after 18 h. Thus, antibiofouling Man-IONPs demonstrated the capability of explicitly imaging CD206(+) M2-like macrophages in vivo and potentials for investigating the dynamics of macrophages in the tumor microenvironment and delivering therapeutics targeting M2-like TAMs.

All-dielectric metasurface absorbers are good candidates for realizing near-unity light absorption within subwavelength-thin nanostructures. However, only moderate quality factor (Q-factor, e.g., Q...

To compare the ovarian responses after administration of two recombinant follicle-stimulating hormone (r-FSH) preparations under gonadotropin-releasing hormone (GnRH) analogue downregulation, we conducted a phase 3, randomized, multicenter, assessor-blind, active-controlled, parallel group study. The primary outcome was the number of oocytes retrieved. The secondary outcomes included total dose and duration of r-FSH administered, oocyte quality, blood estradiol levels, follicular development, fertilization rates, implantation rates, and pregnancy rates (biochemical, clinical, and ongoing). A total of 451 patients with infertility were randomized to receive either Follitrope™ Prefilled Syringe or Gonal-F® Pen for ovarian stimulation. The mean number of oocytes retrieved was 14.9 in the FollitropeTM Prefilled Syringe group, and 12.8 in the Gonal-F® Pen group. The 95% confidence interval in the oocyte number difference between the groups was [-0.1, 4.2], demonstrating that FollitropeTM Prefilled Syringe was not inferior to Gonal-F® Pen. The clinical pregnancy rates (FollitropeTM Prefilled Syringe vs. Gonal-F® Pen: 55.4% vs. 51.9%) and ongoing pregnancy rates (44.1% vs. 43.0%) were similar between the groups. No clinically significant adverse events were observed in either group. In summary, our study indicates that FollitropeTM Prefilled Syringe is safe and efficacious for ovarian stimulation.

Antimüllerian hormone, the most reliable biomarker of ovarian reserve, is widely used in various clinical situations. Antimüllerian hormone levels consistently decrease with age. However, there is no standard, age-specific reference values for antimüllerian hormone in women of reproductive age, which limits its application.This study aimed to establish age-specific antimüllerian hormone percentile reference values for women of reproductive age.A nationwide, population-based cross-sectional survey was conducted between May 2019 and April 2021 in 15 provinces and municipalities in mainland China. A total of 10,053 eligible women aged 20 to 49 years were selected using a multistage stratified sampling procedure. Women who were pregnant, had undergone ovarian surgery, took hormone drugs in the past 3 months, or had an antimüllerian hormone outlier value were excluded from establishing antimüllerian hormone percentile reference values. Serum antimüllerian hormone concentrations were measured using ultrasensitive, 2-site enzyme-linked immunosorbent assays (Ansh Lab, Webster, TX) in the Reproductive Endocrinology Laboratory of Peking University Third Hospital. Generalized additive models for location scale and shape with the Box-Cox t original distribution were used to estimate the fitted antimüllerian hormone percentile reference values.A total of 9112 eligible women aged 21 to 49 years were included in the fitting model. The fitted 50th (2.5th-97.5th) percentiles of antimüllerian hormone values for women aged 21, 25, 30, 35, 40, 45, and 49 years were 4.83 (0.79-18.41), 4.47 (0.72-16.58), 3.67 (0.50-13.82), 2.59 (0.24-10.35), 1.35 (0.05-6.68), 0.33 (0.01 to 3.40), and 0.04 (0.01 to 1.77) ng/mL, respectively. The population-based decline rate of antimüllerian hormone accelerated with increasing age, especially age35 years. The magnitude of the decline of the 25th antimüllerian hormone percentile curve was greater than that of the 75th percentile curve.This study established age-specific antimüllerian hormone percentile reference values for women of reproductive age based on a large representative sample of the general population and described antimüllerian hormone changes. These findings may facilitate antimüllerian hormone application in clinical practices.

The hydrogels, because of their swelling properties in response to the environmental stimulus, are being widely considered for the design of controlled drug release systems. To meet the need for developing effective drug delivery methods, we developed special silica colloidal crystal (SCC)-embedded chitosan hydrogel films. The SCC films served as an interference substrate and drug storage layer, while the chitosan hydrogel served as a cover to regulate the drug release. The optical interferometry was performed to dynamically monitor the volume phase transition of chitosan hydrogel response to pH stimulation. Furthermore, the effects of crosslinking ratio and hydrogel thickness on the swelling properties of chitosan hydrogel were also evaluated. More importantly, the pH-responsive swelling of chitosan hydrogel was used to slowly release indomethacin. This system may provide support for drug delivery studies, therefore further expected to apply in the enhancement of the treatment efficiency of new drug therapies.

PurposeTo compare the effects of early and mid-late follicular phase administration of 150 IU of human chorionic gonadotropin (hCG) on gonadotropin-releasing hormone (GnRH) antagonist protocol in “unpredictable” poor ovarian response (POR) women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment.MethodsA retrospective single-center cohort study was conducted on 67 patients with “unpredictable” POR in their first IVF/ICSI cycle receiving GnRH antagonist protocol. Patients were treated with a second IVF/ICSI cycle using the same GnRH antagonist protocol with the same starting dose of recombinant follicle-stimulating hormone (rFSH) as the first cycle; a daily dose of 150 IU of hCG was administrated on either stimulation day 1 (Group A, n = 35) or day 6 (Group B, n = 32). The number of oocytes retrieved, number of usable embryos, serum level of estradiol (E2) on day of hCG trigger, and clinical pregnant outcomes were studied.ResultsThe addition of 150 IU of hCG on either the first day or sixth day of stimulation increases the serum level of E2, luteinizing hormone (LH), and hCG on the day of hCG trigger. Only the use of 150 IU of hCG on the first stimulation day improved the number of oocytes retrieved, mature of oocytes, and usable embryos, but not the addition of hCG on stimulation day 6. Implantation rate, clinical pregnancy rate, and ongoing pregnancy rate showed an increasing trend in patients receiving 150 IU of hCG in the early phase compared with mid-late phase, even thought there was no statistically significant difference.ConclusionsOur study demonstrated that adding 150 IU of hCG in subsequent GnRH antagonist cycle in “unpredictable” poor responders is associated with the improvement of response to stimulation. Furthermore, early follicular phase addition of 150 IU of hCG significantly increased the number of oocytes retrieved and usable embryos than did the mid-late addition of the same dose.

Background Anopheles sinensis is a dominant vector for malaria transmission in Asian countries. Voltage-gated sodium channel (VGSC) mutation-mediated knock-down resistance (kdr) has developed in many A. sinensis populations because of intensive and long-term use of pyrethroids. Our previous study showed that multiple mutations at position 1014 of the VGSC were heterogeneously distributed in A. sinensis populations across Sichuan, China. Methods To understand resistance genotypes at the haplotype level and reconstruct the phylogenetic relationship of VGSC haplotypes, a cost-effective next-generation sequencing (NGS)-based amplicon sequencing approach was established to clarify haplotypes containing codon 1014 of the VGSC gene from a total of 446 adults collected in 12 locations of Sichuan, China. Results Nineteen (19) haplotypes were identified, including 11 wild 1014L, 6 resistance 1014F, and 2 resistance 1014C haplotypes. We found that resistance haplotypes of A. sinensis VGSC were widely distributed at frequencies ranging from 3.67 to 92.61%. The frequencies of the 1014C haplotype in the southeast of Sichuan (Luzhou, Guangan, and Suining) were relatively higher than those in other sampling locations. Phylogenetic analyses support that kdr-type mutation at position 1014 is not singly originated and resistance 1014C haplotypes evolve from TTT-encoding 1014F. Conclusions A cost-effective next-generation sequencing (NGS)-based amplicon sequencing approach has been established in this study. The data revealed the patchy distribution of VGSC resistance haplotypes with overall high frequencies in Sichuan, China. Phylogenetic analyses support multiple origins and sequential evolution (1014L → 1014F → 1014C) for kdr-type mutations in A. sinensis. Graphical abstract

Noninvasive detection of early-stage liver metastases from different primary cancers is a pressing unmet medical need. The lack of both molecular biomarkers and the sensitive imaging methodology makes the detection challenging. In this study, we observed the elevated expression of chemokine receptor 4 (CXCR4) in uveal melanoma (UM) patient liver tissues, and high CXCR4 expression in liver metastases of UM murine models, regardless of the expression levels in the primary tumors. Based on these findings, we identified CXCR4 as an imaging biomarker and exploited a CXCR4-targeted MRI contrast agent ProCA32.CXCR4 for molecular MRI imaging. ProCA32.CXCR4 has strong CXCR4 binding affinity, high metal selectivity, and r1 and r2 relaxivities, which enables the sensitive detection of liver micrometastases. The MRI imaging capacity for detecting liver metastases was demonstrated in three UM models and one ovarian cancer model. The imaging results were validated by histological and immunohistochemical analysis. ProCA32.CXCR4 has strong potential clinical application for non-invasive diagnosis of liver metastases.

Rationale: "Active targeting" based on the ligand-target affinity is a common strategy to precisely deliver nanoparticle (NP) imaging probes or drug carriers to the diseased tissue. However, such ligand-mediated active targeting inevitably takes place with prerequisite "passive targeting", driven by the enhanced permeability and retention (EPR) effect. Thus, the efficiency of active targeting in relation to off-targeted unbound NPs is of great importance in quantitative imaging of tumor biomarkers and delivery. With the notion that easy clearance of off-targeted uIONPs may lead to enhanced active targeting and tumor accumulation, we examined the NP size effect on "active targeting" of the transferrin receptor (TfR) using transferrin (Tf)-conjugated sub-5 nm (3 nm core) ultrafine iron oxide NPs (uIONPs) and larger IONPs (30 nm core). Methods: Green fluorescent dye (FITC)-labeled active targeting uIONPs (FITC-Tf-uIONPs) and red fluorescent dye (TRITC)-labeled passive targeting uIONPs (TRITC-uIONPs) were prepared. FITC-Tf-IONPs and TRITC-IONPs were used as comparison for the NP size effect. Multiphoton imaging, confocal fluorescence imaging, histological staining and computational analysis were applied to track different types of NPs in tumors at 1, 3 and 24 hours after co-injection of equal amounts of paired NPs, e.g., active targeting FITC-Tf-uIONPs and non-targeting TRITC-uIONPs, or FITC-Tf-IONPs and TRITC-IONPs into the same mice bearing 4T1 mouse mammary tumors. Results: Active targeting uIONPs exhibited an almost 6-fold higher level of tumor retention with deeper penetration comparing to non-targeting uIONPs at 24 hours after co-injection. However, accumulation of active targeting IONPs with a 30-nm core is only about 1.15-fold higher than non-targeting IONPs. The enhanced active targeting by uIONPs can be attributed to the size dependent clearance of unbound off-targeted NPs, as majority off-targeted uIONPs were readily cleared from the tumor by intravasation back into tumor blood vessels likely due to high interstitial pressure, even though they are not favorable for macrophage uptake. Conclusion: Ligand-mediated active targeting improves the delivery and accumulation of the sub-5 nm NPs. The improvement on active targeting is size-dependent and facilitated by NPs with sub-5 nm core sizes. Thus, sub-5 nm NPs may serve as favorable platforms for development of NP-based molecular imaging probes and targeted drug carriers.

Advanced and therapy-resistant prostate tumors often display neural or neuroendocrine behavior. We assessed the consequences of prostate cancer cell interaction with neural cells, which are rich in the human prostate and resident of the prostate tumor. In 3-dimensional co-culture with neurospheres, red fluorescent human LNCaP cells formed agglomerates on the neurosphere surface. Upon induced neural differentiation, some red fluorescent cells showed morphology of fully differentiated neural cells, indicating fusion between the cancer and neural stem cells. These fusion hybrids survived for extended times in a quiescent state. A few eventually restarted cell division and propagated to form derivative hybrid progenies. Clones of the hybrid progenies were highly heterogeneous; most had lost prostatic and epithelial markers while some had acquired neural marker expression. These results indicate that cancer cells can fuse with bystander neural cells in the tumor microenvironment; and cancer cell fusion is a direct route to tumor cell heterogeneity.

With the aim to develop better and more reliable interference effective substrates, silica colloidal crystal films with different sphere diameters and film thicknesses were successfully made by an improved vertical deposition method and a systematic investigation of their reflectometric interference spectroscopy (RIfS) properties are presented in this work. The influence of silica sphere diameter and film thickness on the RIfS signals was studied. The results showed that the film thickness is the key factor of RIfS signals. An RIfS system was set up by using a silica colloidal crystal film as an interference effective substrate. The influence of film thickness on the response to refractive index changes of the proposed system was also investigated. When the influence of film thickness on RIfS signals and refractive index response we considered together, silica colloidal crystal films with a thickness between 4 and 6 μm were chosen for sensor construction. Monitoring the digestive process of gelatin with trypsin was also demonstrated by combining gelatin-modified silica colloidal crystal films with RIfS. The system showed excellent sensitivity with a wide linear range and could achieve real-time measurement of each process. It has been proved that this is a promising method to construct biosensors using silica colloidal crystal films as interference-sensitive substrates.

To detect redox potential and pH simultaneously in rat joints, a surface-enhanced Raman scattering (SERS)-active microneedle was structured with two separate grooves containing redox-sensitive and pH-sensitive SERS probes, respectively. The multiplexed SERS-active microneedles brought the two SERS probes into muscles with minimal invasion to sense their redox status and pH in 5 min, and they also detected the dynamical evolution of redox status and pH in muscles. The multiplexed SERS-active microneedles were also inserted into rat joints to sense their redox status and pH, which lack flowable fluids. The strategy of one SERS probe in one groove would allow SERS-active microneedles to become a multiplexed analytical tool for minimally invasive sampling

One of organic ultraviolet (UV) filters, Octocrylene (OCL), is mainly used in various cosmetic products, which is being frequently detected in soil, sediment, aquatic systems and food chain. There is evidence confirmed the reproductive toxicity of OCL in Japanese medaka. However, less was known about the effects of OCL exposure on oocyte quality. Here, we investigated the impacts of OCL on mouse oocyte maturation and quality by exposing oocytes to OCL in vitro at concentrations of 8, 22, 30, 40 and 50 nM. The results showed that OCL markedly reduced mouse oocyte germinal vesicle breakdown (GVBD) at 50 nM and polar body extrusion (PBE) rates at 40 and 50 nM. OCL exposure further disrupted spindle assembly and chromosome alignment, finally inducing aneuploid. Mitochondrial function was also damaged by OCL exposure, leading to ROS overproduction and apoptosis in oocytes. Moreover, OCL treatment impaired the distribution of cortical granules and sperm binding ability of oocytes. In summary, these data demonstrated that OCL could disturb the oocyte meiotic maturation and reduce oocyte quality.

Immunoglobulin G (IgG) is a significant ingredient of immunological activity in milk and colostrum, the activity and content of which is easily disturbed by potentially conditional variant during sterilization. Therefore, developing robust methods for the detection of IgG levels in milk is especially important. Herein, protein A from the Staphylococcus aureus functionalized silica colloidal crystalline film (SCC@SPA) sensing unit combined with ordered porous layer interferometry (OPLI) for IgG detection in untreated bovine milk was developed. Calibration curves in milk and buffer were set up by the variations of the optical thickness (OT) of the sensing unit after the IgG association and dissociation phases. The influence of temperature on the level of IgG was evaluated. Furthermore, the identification of IgG levels with pasteurized milk and ultrahigh temperature (UHT) sterilized milk from the market randomly was successfully carried out without any sample pretreatment. More importantly, compared with other methods, this novel method has the advantages of convenient operation, low cost, and suitability for point-of-care (POC) testing.

Sensing Microcystin-LR (MC-LR) is an important issue for environmental monitoring, as the MC-LR is a common toxic pollutant found in freshwater bodies. The demand for sensitive detection method of MC-LR at low concentrations can be addressed by metasurface-based sensors, which are feasible and highly efficient. Here, we demonstrate an all-dielectric metasurface for sensing MC-LR. Its working principle is based on quasi-bound states in the continuum mode (QBIC), and it manifests a high-quality factor and high sensitivity. The dielectric metasurface can detect a small change in the refractive index of the surrounding environment with a quality factor of ~170 and a sensitivity of ~788 nm/RIU. MC-LR can be specifically identified in mixed water with a concentration limit of as low as 0.002 μg/L by a specific recognition technique for combined antigen and antibody. Furthermore, the demonstrated detection of MC-LR can be extended to the identification and monitoring of other analytes, such as viruses, and the designed dielectric metasurface can serve as a monitor platform with high sensitivity and high specific recognition capability.

Developing powerful real-time methods for monitoring the thrombolytic process is highly desirable for the early therapy of thrombus diseases. Herein, an optical interference fibrin was constructed, fabricated by assembling a 190 nm silica colloidal crystal on glass slides, for detecting a thrombolytic process through the shift of interference peaks caused by the variation of the thicknesses of a silica colloidal crystal film with loaded fibrin dissolution. The whole kinetic progress of thrombolysis by nattokinase and urokinase as thrombolytic drug models was recorded, and the kinetic data were calculated. Moreover, the developed method shows excellent sensitivity for the activity of nattokinase and urokinase with wide linear ranges of approximately 0.75-750 and 5-1000 units mL-1, respectively. Thus, this method can be used as a real-time, low-cost, and simple system for monitoring the thrombolytic process of drugs, demonstrating huge potential in the development of treating thromboembolic diseases and screening drugs.