Using organoids to investigate human endometrial receptivity

The human endometrium is only receptive to an implanting blastocyst in the mid-secretory phase of each menstrual cycle. Such time-dependent alterations in function require intricate interplay of various factors, largely coordinated by estrogen and progesterone. Abnormal endometrial receptivity is thought to contribute to two-thirds of the implantation failure in humans and therefore significantly hindering IVF success. Despite the incontrovertible importance of endometrial receptivity in implantation, the precise mechanisms involved in the regulation of endometrial receptivity remain poorly defined. This is mainly due to a lack of proper in vitro models that recapitulate the in vivo environment of the receptive human endometrium. Organoids were recently established from human endometrium with promising features to better mimic the receptive phase. Endometrial organoids show long-term expandability and the capability to preserve the structural and functional characteristics of the endometrial tissue of origin. This three-dimensional model maintains a good responsiveness to steroid hormones in vitro and replicates key morphological features of the receptive endometrium in vivo, including pinopodes and pseudostratified epithelium. Here, we review the current findings of endometrial organoid studies that have been focused on investigating endometrial receptivity and place an emphasis on methods to further refine and improve this model

Approaches to enhance electroluminescent efficiency of light-emitting diodes based on quasi-two-dimensional perovskite

Quasi-two-dimensional (quasi-2D) perovskites with (Ai)2(A2)n-iPbnX3n+i multi-quantum well structures are considered as the potential electroluminescence (EL) materials due to their controllable quantum confine effect which would lead a high EL efficiency. However, the quasi-2D perovskite films fabricated with solution processing technologies consist of different n phases and orientated layers, which limits the performance of quasi-2D perovskite light- emitting diodes (PeLEDs). To improve the performance of PeLEDs, it is essential to obtain perovskite thin films with both large exciton binding energy, complete surface coverage and suitable morphology. Here some approaches are developed to improve the performance of quasi-2D PeLEDs

Study of the current status and factors that influence indoor air pollution in 138 houses in the urban area in Xi'an

Indoor air pollutants were monitored in 138 households in urban Xi'an that were recently decorated, and the concentrations of formaldehyde, total volatile organic compounds (TVOC), amines, benzene, methylbenzol, xylene, and radon were monitored in the bedrooms, sitting rooms, dinning rooms, kitchens, bathrooms, and studies of the houses. The most seriously elevated pollutants were TVOC and formaldehyde, whose rates exceeded standards by 69.8% and 60.8%, respectively. Ammonia was 13.2% above the standard, and xylene was 8.7% above the standard. The level of radon in 100% of the rooms was below the standard. Only for formaldehyde were there statistically significant differences in concentrations in the sitting room, bedroom, and study (P < 0.05). Concentrations of TVOC, amines, and xylene were positively related to the concentration of formaldehyde in the same room. The concentrations of the major pollutants in summer were highest and had a statistically significant difference with those in other seasons. TVOC and formaldehyde were the most serious pollutants indoors after decorating in an urban area of Xi'an. The concentrations of formaldehyde in the sitting rooms were different than in other types of rooms. Formaldehyde can be a representative of the levels of pollutants indoors; rooms with a higher concentration of formaldehyde tend to have higher levels of other pollutants. In addition, pollutants in the decorated rooms have a strong positive dependence on the monitoring seasons. Summer was the peak time of indoor pollutant levels. Households should pay extra attention to ventilation and take other effective measures to avoid health problems caused by indoor air pollutants

A Benchmark for Accurate GPCR Ligand Binding Affinity Prediction with Free Energy Perturbation

G protein-coupled receptors (GPCRs) are among the most important drug targets in the pharmaceutical industry. Free energy perturbation (FEP), which can accurately predict the relative binding free energies of drug molecules, is now widely used in drug discovery. With the development of structural biology tools such as cryoelectron-microscopy (cryo-EM), the structures of a large number of GPCRs have been resolved, which provides the basis for FEP calculations. In this study, we developed an FEP protocol for GPCR FEP calculation. We performed calculations on 226 perturbation pairs of 139 ligands against 8 GPCRs, spanning 12 datasets (A2A , mGlu5 , D3, OX2 , CXCR4, β1, δ and TA1 receptors) and obtained promising results, particularly for agonist ligands in the TA1 datasets (R2, 0.58, RMSE, 1.07 kcal · mol−1 ). The average R2 is 0.61 and the average RMSE is 0.94 kcal · mol−1 , which is comparable to experimental accuracy(<1 kcal · mol−1 ). We also investigated factors that impact the accuracy of FEP results, including ligand binding pose, water placement, and protein structure. Our input structures for FEP calculation are publicly available as a benchmark dataset for future GPCR-FEP studies (https://doi.org/10.5281/zenodo.7988248). This represents the largest collection of GPCR FEP calculations known to us thus far. This work is expected to significantly contribute to the advancement of GPCR-targeted drug discovery

Biomimetic “Gemini nanoimmunoregulators” orchestrated for boosted photoimmunotherapy by spatiotemporally modulating PD-L1 and tumor-associated macrophages

A novel strategy of not only stimulating the immune cycle but also modulating the immunosuppressive tumor microenvironment is of vital importance to efficient cancer immunotherapy. Here, a new type of spatiotemporal biomimetic “Gemini nanoimmunoregulators” was engineered to activate robust systemic photoimmunotherapy by integrating the triple-punch of amplified immunogenic cell death (ICD), tumor-associated macrophages (TAMs) phenotype reprogramming and programmed cell death ligand 1 (PD-L1) degradation. The “Gemini nanoimmunoregulators” PM@RM-T7 and PR@RM-M2 were constructed by taking the biocompatible mesoporous polydopamine (mPDA) as nanovectors to deliver metformin (Met) and toll-like receptor 7/8 agonist resiquimod (R848) to cancer cells and TAMs by specific biorecognition via wrapping of red blood cell membrane (RM) inlaid with T7 or M2 peptides. mPDA/Met@RM-T7 (abbreviated as PM@RM-T7) was constructed to elicit an amplified in situ ICD effect through the targeted PTT and effectively stimulated the anticancer immunity. Meanwhile, PD-L1 on the remaining cancer cells was degraded by the burst metformin to prevent immune evasion. Subsequently, mPDA/R848@RM-M2 (abbreviated as PR@RM-M2) specifically recognized TAMs and reset the phenotype from M2 to M1 state, thus disrupting the immunosuppressive microenvironment and further boosting the function of cytotoxic T lymphocytes. This pair of sister nanoimmunoregulators cooperatively orchestrated the comprehensive anticancer activity, which remarkably inhibited the growth of primary and distant 4T1 tumors and prevented malignant metastasis. This study highlights the spatiotemporal cooperative modalities using multiple nanomedicines and provides a new paradigm for efficient cancer immunotherapy against metastatic-prone tumors