The density of the inner cell mass is a new indicator of the quality of a human blastocyst: a valid supplement to the Gardner scoring system.

STUDY QUESTION: Can the density of the inner cell mass (ICM) be a new indicator of the quality of the human blastocyst? SUMMARY ANSWER: The densification index (DI) developed in this study can quantify ICM density and provide positive guidance for ploidy, pregnancy, and live birth. WHAT IS KNOWN ALREADY: In evaluating the quality of ICM, reproductive care clinics still use size indicators without further evaluation. The main disadvantage of this current method is that the evaluation of blastocyst ICM is relatively rough and cannot meet the needs of clinical embryologists, especially when multiple blastocysts have the same ICM score, which makes them difficult to evaluate further. STUDY DESIGN, SIZE, DURATION: This observational study included data from 2272 blastocysts in 1991 frozen-thawed embryo transfer (FET) cycles between January 2018 to November 2021 and 1105 blastocysts in 430 preimplantation genetic testing cycles between January 2019 and February 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: FET, ICSI, blastocyst culture, trophectoderm biopsy, time-lapse (TL) monitoring, and next-generation sequencing were performed. After preliminary sample size selection, the 11 focal plane images captured by the TL system were normalized and the spatial frequency was used to construct the DI of the ICM. MAIN RESULTS AND THE ROLE OF CHANCE: This study successfully constructed a quantitative indicator DI that can reflect the degree of ICM density in terms of fusion and texture features. The higher the DI value, the better the density of the blastocyst ICM, and the higher the chances that the blastocyst was euploid (P < 0.001) and that pregnancy (P < 0.001) and live birth (P = 0.005) were reached. In blastocysts with ICM graded B and blastocysts graded 4BB, DI was also positively associated with ploidy, pregnancy, and live birth (P < 0.05). ROC analysis showed that combining the Gardner scoring system with DI can more effectively predict pregnancy and live births, when compared to using the Gardner scoring system alone. LIMITATIONS, REASONS FOR CAUTION: Accurate calculation of the DI value places high demands on image quality, requiring manual selection of the clearest focal plane and exposure control. Images with the ICM not completely within the field of view cannot be used. The association between the density of ICM and chromosomal mosaicism was not evaluated. The associations between the density of ICM and different assisted reproductive technologies and different culture conditions in embryo laboratories were also not evaluated. Prospective studies are needed to further investigate the impact of ICM density on clinical outcomes. WIDER IMPLICATIONS OF THE FINDINGS: ICM density assessment is a new direction in blastocyst assessment. This study explores new ways of assessing blastocyst ICM density and develops quantitative indicators and a corresponding qualitative evaluation scheme for ICM density. The DI of the blastocyst ICM developed in this study is easy to calculate and requires only TL equipment and image processing, providing positive guidance for clinical outcomes. The qualitative evaluation scheme of ICM density can assist embryologists without TL equipment to manually evaluate ICM density. ICM density is a simple indicator that can be used in practice and is a good complement to the blastocyst scoring systems currently used in most centers. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Key Research & Development Program of China (2021YFC2700603). The authors report no financial or commercial conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

A ZIF-90 nanoplatform loaded with an enzyme-responsive organic small-molecule probe for imaging the hypoxia status of tumor cells.

Hypoxia is one of the most common and important features occurring across a wide variety of malignancies, which can have adverse effects on the therapeutic outcomes of chemotherapy and radiotherapy. Therefore, the characterization of tumor hypoxia is of great importance in clinical tumor treatment. Herein, we firstly develop a new spectroscopic off-on probe with high sensitivity (detection limit: 5.8 ng mL-1) and good selectivity for fluorescence imaging the hypoxic status of tumor cells via its enzymatic reaction with nitroreductase in vitro and in vivo in the presence of dimethyl sulfoxide (DMSO) as a co-solvent. Inspired by the recent investigations on metal-organic frameworks (MOFs), a dual pH and ATP-responsive ZIF-90 nanoplatform was synthesized, and then PEG was post-modified through a Schiff base reaction. This allows the platform to serve as a carrier to load the hypoxia-responsive probe to investigate its response to enzyme in cells and in mice without using dimethyl sulfoxide as a co-solvent. Consequently, the two probes we synthesized here can successfully respond to nitroreductase for turn-on fluorescence imaging at a cellular level and in tumor-bearing mice. This is the first time that an enzyme-responsive organic small-molecule probe has been mounted on one of the MOFs. Our results open up a promising way for the design and application of both enzyme-responsive probes and MOFs.

Correction: Layered bismuth oxyhalide nanomaterials for highly efficient tumor photodynamic therapy.

Correction for 'Layered bismuth oxyhalide nanomaterials for highly efficient tumor photodynamic therapy' by Yu Xu, et al., Nanoscale, 2016, DOI: 10.1039/c5nr04540a.

Layered bismuth oxyhalide nanomaterials for highly efficient tumor photodynamic therapy.

Layered bismuth oxyhalide nanomaterials have received much more interest as promising photocatalysts because of their unique layered structures and high photocatalytic performance, which can be used as potential inorganic photosensitizers in tumor photodynamic therapy (PDT). In recent years, photocatalytic materials have been widely used in PDT and photothermal therapy (PTT) as inorganic photosensitizers. This investigation focuses on applying layered bismuth oxyhalide nanomaterials toward cancer PDT, an application that has never been reported so far. The results of our study indicate that the efficiency of UV-triggered PDT was highest when using BiOCl nanoplates followed by BiOCl nanosheets, and then TiO2. Of particular interest is the fact that layered BiOCl nanomaterials showed excellent PDT effects under low nanomaterial dose (20 µg mL(-1)) and low UV dose (2.2 mW cm(-2) for 10 min) conditions, while TiO2 showed almost no therapeutic effect under the same parameters. BiOCl nanoplates and nanosheets have shown excellent performance and an extensive range of applications in PDT.

A Near Infrared Light Triggered Hydrogenated Black TiO2 for Cancer Photothermal Therapy.

White TiO2 nanoparticles (NPs) have been widely used for cancer photodynamic therapy based on their ultraviolet light-triggered properties. To date, biomedical applications using white TiO2 NPs have been limited, since ultraviolet light is a well-known mutagen and shallow penetration. This work is the first report about hydrogenated black TiO2 (H-TiO2 ) NPs with near infrared absorption explored as photothermal agent for cancer photothermal therapy to circumvent the obstacle of ultraviolet light excitation. Here, it is shown that photothermal effect of H-TiO2 NPs can be attributed to their dramatically enhanced nonradiative recombination. After polyethylene glycol (PEG) coating, H-TiO2 -PEG NPs exhibit high photothermal conversion efficiency of 40.8%, and stable size distribution in serum solution. The toxicity and cancer therapy effect of H-TiO2 -PEG NPs are relative systemically evaluated in vitro and in vivo. The findings herein demonstrate that infrared-irradiated H-TiO2 -PEG NPs exhibit low toxicity, high efficiency as a photothermal agent for cancer therapy, and are promising for further biomedical applications.

Stability enhanced polyelectrolyte-coated gold nanorod-photosensitizer complexes for high/low power density photodynamic therapy.

Photodynamic therapy (PDT) is a promising treatment modality for cancer and other malignant diseases, however safety and efficacy improvements are required before it reaches its full potential and wider clinical use. Herein, we investigated a highly efficient and safe photodynamic therapy procedure by developing a high/low power density photodynamic therapy mode (high/low PDT mode) using methoxypoly(ethylene glycol) thiol (mPEG-SH) modified gold nanorod (GNR)-AlPcS4 photosensitizer complexes. mPEG-SH conjugated to the surface of simple polyelectrolyte-coated GNRs was verified using Fourier transform infrared spectroscopy; this improved stability, reduced cytotoxicity, and increased the encapsulation and loading efficiency of the nanoparticle dispersions. The GNR-photosensitizer complexes were exposed to the high/low PDT mode (high light dose = 80 mW/cm(2) for 0.5 min; low light dose = 25 mW/cm(2) for 1.5 min), and a high PDT efficacy leads to approximately 90% tumor cell killing. Due to synergistic plasmonic photothermal properties of the complexes, the high/low PDT mode demonstrated improved efficacy over using single wavelength continuous laser irradiation. Additionally, no significant loss in viability was observed in cells exposed to free AlPcS4 photosensitizer under the same irradiation conditions. Consequently, free AlPcS4 released from GNRs prior to cellular entry did not contribute to cytotoxicity of normal cells or impose limitations on the use of the high power density laser. This high/low PDT mode may effectively lead to a safer and more efficient photodynamic therapy for superficial tumors.

Joint derivation method for determining optical properties based on steady-state spatially resolved diffuse reflectance measurement at small source-detector separations and large reduced albedo range: theory and simulation.

Accurate determination of the optical properties (the absorption coefficient µ(a) and the reduced scattering coefficient µ(s) (')) of tissues is very important in a variety of diagnostic and therapeutic procedures. Optical diffusion theory is frequently used as the forward model for describing the photon transfer in media with large reduced albedos (a(')) and in large source-detector separations (SDS). Several other methods (PN approximation, hybrid diffusion-P3 approximation) have also been published that describe photon transfer in media with low a(') or small SDSs. We studied the theoretical models for the steady-state spatially resolved diffuse reflectance measurement to accurately determine µ(a) and µ(s) (') at large a(') range but small SDSs. Instead of using a single model, a joint derivation method is proposed. The developed method uses one of the best aforementioned theoretical methods separately in five ranges of a(') determined from several forward models. In the region of small SDSs (the range between 0.4 and 8 mm) and large a(') range (between 0.5 and 0.99), the best theoretical derivation model was determined. The results indicate that the joint derivation method can improve the derivation accuracy and that a(') range can be determined by the steady-state spatially resolved diffuse reflectance measurement.

Hybrid diffusion-P3 equation in N-layered turbid media: steady-state domain.

This paper discusses light propagation in N-layered turbid media. The hybrid diffusion-P3 equation is solved for an N-layered finite or infinite turbid medium in the steady-state domain for one point source using the extrapolated boundary condition. The Fourier transform formalism is applied to derive the analytical solutions of the fluence rate in Fourier space. Two inverse Fourier transform methods are developed to calculate the fluence rate in real space. In addition, the solutions of the hybrid diffusion-P3 equation are compared to the solutions of the diffusion equation and the Monte Carlo simulation. For the case of small absorption coefficients, the solutions of the N-layered diffusion equation and hybrid diffusion-P3 equation are almost equivalent and are in agreement with the Monte Carlo simulation. For the case of large absorption coefficients, the model of the hybrid diffusion-P3 equation is more precise than that of the diffusion equation. In conclusion, the model of the hybrid diffusion-P3 equation can replace the diffusion equation for modeling light propagation in the N-layered turbid media for a wide range of absorption coefficients.

A reference-wavelength-based method for improved analysis of near-infrared spectroscopy.

Near-infrared (NIR) spectroscopy has been widely used in many industrial applications. It also has tremendous potential for trace element detection and noninvasive human physiological measurements. In NIR spectroscopy, however, the measurement precision is often dependent on temperature, measurement position, and sample status. In order to improve measurement precision, a method using spectral information at a reference wavelength is developed in this paper. Based on the displacement effect between solvent and solute molecules in a solution, the signal at the reference wavelength is used as an internal reference to correct the spectrum of the sample under test. As an example, the spectra of glucose aqueous solutions under different temperatures are measured, and our method for eliminating the temperature disturbance is evaluated. The experimental results obtained show that the relative error of glucose concentration prediction is 330% per degree before the spectrum correction. After the correction, the relative error is reduced to 5.12%, and the error is no longer dependent on temperature. As the displacement effect can be found commonly in various solutions, the method described in this work may be used to improve the accuracy of spectral analysis of many other solutions.

[Study on temperature correction of near-infrared spectra of solution].

The near-infrared spectrum of some common solvents, such as water, has very high sensitivity to temperature. So, the effect of temperature can not be ignored in NIRS. When temperature changes, the transmission spectra of the solution will also change. The influence of the temperature was deduced theoretically based on the Lambert-Beer's law in the present paper. And a method for temperature correction of sample's spectra was proposed. By using the change in pure solvent's absorbency with temperature disturbance, the method is used to correct the spectra of prediction samples. The spectra of glucose aqueous solution and albumin aqueous solution were measured at different temperatures. The calibration models of glucose and albumin concentration prediction were built respectively by using the calibration sample's spectra at 30 degrees C. The absorbency of pure water has different value at different temperature, and this difference was used to correct the spectra of sample which was measured at temperatures other than 30 degrees C. The experiment results showed that the curves of absorbancy difference of prediction samples, which were measured at different temperatures, show good superposition after spectra correction. And the root mean square error (RMSEP) of prediction was reduced obviously. It also means that the influence of temperature on the spectra can be eliminated effectively after spectra correction by using the method proposed in this paper.

[Study on the pathological uterine tissues with a fiber Raman spectrometry].

The Raman spectrum can reflect the differences in chemical components and molecular structures of tissues and cells, and significant progress has been made in the research on structures, functions and diseases of cells and tissues with Raman spectroscopy. A fiber Raman spectrometer was used to measure the Raman spectra of some uterine malignant, benign, and normal tissues, such as uterine myometrium tissue, uterine myoma tissue, normal endometrium tissue, malignant endometrium tissue and adenomyosis tissue. After having compared the Raman spectrum of pathological tissues with that of the corresponding normal tissues, we observed that the peak referring to Methionine upsilon(C--S) (Met upsilon(C--S)) splits into two peaks in the uterine myoma tissues caused by the vibrations of tryptophan (Trp) and cartotene, which are not present in the normal tissues. There is a peak at 1447 cm(-1) in the endometrium tissues corresponding to CH2--CH3 def, which is one of the characteristic peaks of cancerous tissues. For the adenomyosis tissues, a peak caused by upsilon(C--C) skeletal-alpha helix is obviously weaker than that in normal tissue, and the peak induced by delta(C--O) shifts from 1160 cm(-1) in normal tissues to 1173 cm(-1) in the adenomyosis tissues. Thus, it was demonstrated that the technology of Raman spectroscopy is available for distinguishing different pathological uterine tissues at molecular level. This study is not only helpful on early diagnosis of uterine diseases, but also very crucial for the basic research on uterine diseases. And the Raman spectroscopy technology based on optic-fibers has a potential to evolve into a highly sensitive technology for diagnosis.