Local glucose elevation activates pyroptosis via NLRP3 inflammasome in ovarian granulosa cells of overweight patients.

Overweight, with an increasing prevalence worldwide, significantly impairs the clinical outcomes following in vitro fertilization (IVF). Hyperglycemia, hyperlipidemia, and metabolic disorders are always accompanied by the majority of overweight patients. The association between granulosa cell function and metabolic alterations in follicular fluid including lipids, proteins, and growth factors has been extensively documented. However, the effects of higher glucose level on ovarian granulosa cells (GCs), remain largely unknown. In this study, we identified that overweight women had elevated follicular glucose level which profoundly activated NLRP3 inflammasome and pyroptosis. An in vitro correlation between follicular high glucose, NLRP3 inflammasome and pyroptosis was also established. More importantly, in granulosa cells of overweight patients, the activation of the NLRP3 inflammasome and pyroptosis induced by high glucose was involved in the dysregulation of estradiol synthesis. Our study may provide new options to interpretate and improve IVF outcomes in overweight women.

Increased expression of HOXA11-AS attenuates endometrial decidualization in recurrent implantation failure patients.

Endometrial decidualization is a prerequisite for implantation, and impaired decidualization is associated with recurrent implantation failure (RIF). Coding genes of the HOX family have been clarified as critical regulators in endometrial decidualization, but the role of long non-coding RNAs (lncRNAs) in the HOX gene family has yet to be determined. The aim of this study was to clarify the possible roles of lncRNAs in the HOX gene family in decidualization. In this study, we identified that HOXA11-AS was the most reduced lncRNA in the HOX family in the human endometrium during the window of implantation, and it was elevated in RIF patients. Mechanistically, HOXA11-AS negatively regulated decidualization through competitive interaction with PTBP1, an RNA-binding protein. Binding of PTBP1 to HOXA11-AS limited PTBP1 availability to regulate PKM1/2 alternative splicing, resulting in enhanced PKM1 and diminished PKM2 expression, thus attenuating decidualization. The pattern of high HOXA11-AS expression and impaired PKM2 splicing was consistently observed in RIF patients. Collectively, our study indicates that the increase of HOXA11-AS is detrimental to endometrial decidualization, likely contributing to RIF. Our study may shed light on the pathogenesis and treatment of RIF.

Elevated SAA1 promotes the development of insulin resistance in ovarian granulosa cells in polycystic ovary syndrome.

BACKGROUND: Insulin resistance (IR) contributes to ovarian dysfunctions in polycystic ovarian syndrome (PCOS) patients. Serum amyloid A1 (SAA1) is an acute phase protein produced primarily by the liver in response to inflammation. In addition to its role in inflammation, SAA1 may participate in IR development in peripheral tissues. Yet, expressional regulation of SAA1 in the ovary and its role in the pathogenesis of ovarian IR in PCOS remain elusive. METHODS: Follicular fluid, granulosa cells and peripheral venous blood were collected from PCOS and non-PCOS patients with and without IR to measure SAA1 abundance for analysis of its correlation with IR status. The effects of SAA1 on its own expression and insulin signaling pathway were investigated in cultured primary granulosa cells. RESULTS: Ovarian granulosa cells were capable of producing SAA1, which could be induced by SAA1 per se. Moreover, the abundance of SAA1 significantly increased in granulosa cells and follicular fluid in PCOS patients with IR. SAA1 treatment significantly attenuated insulin-stimulated membrane translocation of glucose transporter 4 and glucose uptake in granulosa cells through induction of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression with subsequent inhibition of Akt phosphorylation. These effects of SAA1 could be blocked by inhibitors for toll-like receptors 2/4 (TLR 2/4) and nuclear factor kappa light chain enhancer of activated B (NF-κB). CONCLUSIONS: Human granulosa cells are capable of feedforward production of SAA1, which significantly increased in PCOS patients with IR. Excessive SAA1 reduces insulin sensitivity in granulosa cells via induction of PTEN and subsequent inhibition of Akt phosphorylation upon activation of TLR2/4 and NF-κB pathway. These findings highlight that elevation of SAA1 in the ovary promotes the development of IR in granulosa cells of PCOS patients.

Elevated levels of arachidonic acid metabolites in follicular fluid of PCOS patients.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women usually accompanied by lipid metabolic disorders. However, it remains unknown whether arachidonic acid (AA) and its metabolites in follicular fluid (FF) were altered in PCOS patients. This study was intended to measure the levels of AA and its metabolites in the FF of non-obese PCOS patients that underwent in vitro fertilization (IVF) and to explore the possible causes of the alterations. Thirty-nine non-obese women with PCOS and 30 non-obese women without PCOS were enrolled. AA and its metabolites were measured by liquid chromatography-mass spectrometry. The levels of AA metabolites generated via cyclooxygenase-2 (COX-2) pathway and cytochrome P450 epoxygenase pathway but not lipoxygenase (LOX) pathway were significantly higher in the FF of PCOS patients. The metabolites generated via COX-2 pathway were significantly correlated with levels of testosterone and fasting insulin in serum. The in vitro study further demonstrated that insulin but not testosterone could promote the IL-1ß and hCG-induced COX-2 expression and prostaglandin E2 (PGE2) secretion in primary human granulosa cells. In conclusion, there was an elevation in AA metabolites in FF of PCOS patients. Insulin played a pivotal role in the increased AA metabolites generated via COX-2, which could be interpreted as another novel molecular pathophysiological mechanism of PCOS.

Microwave Speech Recognizer Empowered by a Programmable Metasurface.

Speech recognition becomes increasingly important in the modern society, especially for human-machine interactions, but its deployment is still severely thwarted by the struggle of machines to recognize voiced commands in challenging real-life settings: oftentimes, ambient noise drowns the acoustic sound signals, and walls, face masks or other obstacles hide the mouth motion from optical sensors. To address these formidable challenges, an experimental prototype of a microwave speech recognizer empowered by programmable metasurface is presented here that can remotely recognize human voice commands and speaker identities even in noisy environments and if the speaker's mouth is hidden behind a wall or face mask. The programmable metasurface is the pivotal hardware ingredient of the system because its large aperture and huge number of degrees of freedom allows the system to perform a complex sequence of sensing tasks, orchestrated by artificial-intelligence tools. Relying solely on microwave data, the system avoids visual privacy infringements. The developed microwave speech recognizer can enable privacy-respecting voice-commanded human-machine interactions is experimentally demonstrated in many important but to-date inaccessible application scenarios. The presented strategy will unlock new possibilities and have expectations for future smart homes, ambient-assisted health monitoring, as well as intelligent surveillance and security.

Ovarian ferroptosis induced by androgen is involved in pathogenesis of PCOS.

STUDY QUESTION: Does ovarian ferroptosis play an active role in the development of polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Increased ovarian ferroptosis was present in PCOS ovaries and the inhibition of ferroptosis with ferrostatin-1 (Fer-1) ameliorated polycystic ovary morphology and anovulation. WHAT IS KNOWN ALREADY: Programmed cell death plays a fundamental role in ovarian follicle development. However, the types and mechanisms of cell death involved in the ovary are yet to be elucidated. Ferroptosis is a recently discovered iron-dependent programmed cell death. Impaired iron metabolism and cell death have been observed in women with PCOS, the main cause of anovulatory infertility. Additionally, previous studies reported that an abnormal expression of noncoding RNA may promote ferroptosis in immortalized ovarian granulosa cell lines. However, little is known about whether ovarian ferroptosis is increased in PCOS, and there is insufficient direct evidence for a role of ferroptosis in PCOS, and the underlying mechanism. Moreover, the effect of the inhibition of ferroptosis with Fer-1 in PCOS remains unclear. STUDY DESIGN SIZE DURATION: Ferroptosis was evaluated in human granulosa cells (hGCs) from non-PCOS (n = 6-16) and PCOS (n = 7-18) patients. The experimental study was completed in vitro using primary hGCs from women undergoing IVF. Improvements in PCOS indicators following ferroptosis inhibition with Fer-1 were investigated in a dehydroepiandrosterone (DHEA)-induced PCOS rat model (n = 8 per group). PARTICIPANTS/MATERIALS SETTING METHODS: Ovarian ferroptosis was evaluated in the following ways: by detecting iron concentrations via ELISA and fluorescent probes; measuring malondialdehyde (MDA) concentrations via ELISA; assessing ferroptosis-related protein abundance with western blotting; observing mitochondrial morphology with transmission electron microscopy; and determining cell viability. Primary hGCs were collected from women undergoing IVF. They were treated with dihydrotestosterone (DHT) for 24 h. The effect of DHT on ferroptosis was examined in the presence or absence of small interfering RNA-mediated knockdown of the putative receptor coregulator for signaling molecules. The role of ovarian ferroptosis in PCOS progression was explored in vivo in rats. The DHEA-induced PCOS rat model was treated with the ferroptosis inhibitor, Fer-1, and the oocytes and metaphase II oocytes were counted after ovarian stimulation. Additionally, rats were treated with the ferroptosis inducer, RSL3, to further explore the effect of ferroptosis. The concentrations of testosterone, FSH, and LH were assessed. MAIN RESULTS AND THE ROLE OF CHANCE: Increased ferroptosis was detected in the ovaries of patients with PCOS and in rats with DHEA-induced PCOS. Increased concentrations of Fe2+ (P < 0.05) and MDA (P < 0.05), and upregulated nuclear receptor coactivator 4 protein levels, and downregulated ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4) proteins were observed in the hGCs in patients with PCOS and ovaries of PCOS rats (P < 0.05 versus control). DHT was shown to induce ferroptosis via activation of NOCA4-dependent ferritinophagy. The inhibition of ferroptosis with Fer-1 in rats ameliorated a cluster of PCOS traits including impaired glucose tolerance, irregular estrous cycles, reproductive hormone dysfunction, hyperandrogenism, polycystic ovaries, anovulation, and oocyte quality (P < 0.05). Treating rats with RSL3 resulted in polycystic ovaries and hyperandrogenism (P < 0.05). LARGE-SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: Although ovarian-targeted ferroptosis inhibition may be a more targeted treatment for PCOS, the underlying mechanisms in the cycle between ferroptosis and hyperandrogenism require further exploration. Additionally, since PCOS shows high heterogeneity, it is important to investigate whether ferroptosis increases are present in all patients with PCOS. WIDER IMPLICATIONS OF THE FINDINGS: Androgen-induced ovarian ferroptosis appears to play a role in the pathogenesis of PCOS, which potentially makes it a promising treatment target in PCOS. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the National Key R&D Program of China (2023YFC2705500, 2023YFC2705505, 2019YFA0802604), National Natural Science Foundation of China (No. 82130046, 82320108009, 82101708, 82101747, and 82001517), Shanghai leading talent program, Innovative research team of high-level local universities in Shanghai (No. SHSMU-ZLCX20210201, No. SSMU-ZLCX20180401), Shanghai Jiaotong University School of Medicine, Affiliated Renji Hospital Clinical Research Innovation Cultivation Fund Program (RJPY-DZX-003) and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (No. 20161413), Shanghai's Top Priority Research Center Construction Project (2023ZZ02002), and Three-Year Action Plan for Strengthening the Construction of the Public Health System in Shanghai (GWVI-11.1-36). The authors report no competing interests.

Intelligent indoor metasurface robotics.

Intelligent indoor robotics is expected to rapidly gain importance in crucial areas of our modern society such as at-home health care and factories. Yet, existing mobile robots are limited in their ability to perceive and respond to dynamically evolving complex indoor environments because of their inherently limited sensing and computing resources that are, moreover, traded off against their cruise time and payload. To address these formidable challenges, here we propose intelligent indoor metasurface robotics (I2MR), where all sensing and computing are relegated to a centralized robotic brain endowed with microwave perception; and I2MR's limbs (motorized vehicles, airborne drones, etc.) merely execute the wirelessly received instructions from the brain. The key aspect of our concept is the centralized use of a computation-enabled programmable metasurface that can flexibly mold microwave propagation in the indoor wireless environment, including a sensing and localization modality based on configurational diversity and a communication modality to establish a preferential high-capacity wireless link between the I2MR's brain and limbs. The metasurface-enhanced microwave perception is capable of realizing low-latency and high-resolution three-dimensional imaging of humans, even around corners and behind thick concrete walls, which is the basis for action decisions of the I2MR's brain. I2MR is thus endowed with real-time and full-context awareness of its operating indoor environment. We implement, experimentally, a proof-of-principle demonstration at ∼2.4 GHz, in which I2MR provides health-care assistance to a human inhabitant. The presented strategy opens a new avenue for the conception of smart and wirelessly networked indoor robotics.

iTRAQ-based Proteomic Analysis Unveils ACSL4 as a Novel Potential Regulator of Human Endometrial Receptivity.

Competent endometrial receptivity is a prerequisite for successful embryo implantation. Identification of novel key molecules involved in endometrial receptivity is essential to better interpret human implantation and improve pregnancy rates in assisted reproduction treatment. Isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics was performed to profile the proteomes of the prereceptive (luteinizing hormone [LH] + 2, n = 4) and receptive (LH + 7, n = 4) endometrial tissues. A total of 173 differentially expressed proteins (DEPs) between LH + 2 and LH + 7 endometrial samples were identified. Integrated analysis of the proteomic data and published transcriptomic data was performed to identify the concordant DEPs with differential expression at both the messenger RNA and protein levels. Protein-protein interaction (PPI) network analysis was performed on concordant DEPs. We first identified 63 novel concordant DEPs and 5 hub proteins (ACSL4, ACSL5, COL1A1, PTGS1, and PLA2G4F) between LH + 2 and LH + 7 endometrial samples. ACSL4 was predominantly expressed in endometrial epithelial cells and its expression was significantly upregulated by progesterone in the LH + 7 endometrium and significantly downregulated in repeated implantation failure patients. Knockdown of ACSL4 in endometrial epithelial cells induced the downregulation of endometrial receptivity markers (HOXA10, COX2, and LIF) and the significant decrease of implantation rate during in vitro implantation analysis. This study provides the first gel-independent quantitative proteomes of the LH + 2 and LH + 7 human endometrium using iTRAQ technology. The identified concordant DEPs and hub proteins open a new avenue for future studies aimed at elucidating the underlying mechanisms governing endometrial receptivity. ACSL4 was identified as a novel regulatory molecule in the establishment of endometrial receptivity and might play important roles during implantation.

The effect of peak serum estradiol level during ovarian stimulation on cumulative live birth and obstetric outcomes in freeze-all cycles.

Objective: To determine whether the peak serum estradiol (E2) level during ovarian stimulation affects the cumulative live birth rate (CLBR) and obstetric outcomes in freeze-all cycles. Methods: This retrospective cohort study involved patients who underwent their first cycle of in vitro fertilization followed by a freeze-all strategy and frozen embryo transfer cycles between January 2014 and June 2019 at a tertiary care center. Patients were categorized into four groups according to quartiles of peak serum E2 levels during ovarian stimulation (Q1-Q4). The primary outcome was CLBR. Secondary outcomes included obstetric and neonatal outcomes of singleton and twin pregnancies. Poisson or logistic regression was applied to control for potential confounders for outcome measures, as appropriate. Generalized estimating equations were used to account for multiple cycles from the same patient for the outcome of CLBR. Results: A total of 11237 patients were included in the analysis. Cumulatively, live births occurred in 8410 women (74.8%). The live birth rate (LBR) and CLBR improved as quartiles of peak E2 levels increased (49.7%, 52.1%, 54.9%, and 56.4% for LBR; 65.1%, 74.3%, 78.4%, and 81.6% for CLBR, from the lowest to the highest quartile of estradiol levels, respectively, P<0.001). Such association remained significant for CLBR after accounting for potential confounders in multivariable regression models, whereas the relationship between LBR and peak E2 levels did not reach statistical significance. In addition, no significant differences were noticed in adverse obstetric and neonatal outcomes (gestational diabetes mellitus, pregnancy-induced hypertension, preeclampsia, placental disorders, preterm birth, low birthweight, and small for gestational age) amongst E2 quartiles for either singleton or twin live births, both before and after adjustment. Conclusion: In freeze-all cycles, higher peak serum E2 levels during ovarian stimulation were associated with increased CLBR, without increasing the risks of adverse obstetric and neonatal outcomes.

Correction to: Amelioration of radiation­induced liver damage by p-coumaric acid in mice.

[This corrects the article DOI: 10.1007/s10068-022-01118-8.].

Amelioration of radiation-induced liver damage by p-coumaric acid in mice.

Radiation-induced liver damage (RILD) is a spiny problem in radiotherapy or other circumstances that exposure to radiation. The need for radioprotective agent is increasing to protect liver tissue. This study aimed to explore the hepatoprotective effect of p-coumaric acid (CA) against RILD. C57BL/6 male mice were exposed to 4 Gy irradiation and administrated with CA for 4 days starting on the same day of irradiation. Mice were sacrificed to obtain blood and liver tissues on day 3.5 or 14 post irradiation, respectively. The blood and liver tissues were collected. As compared with the only irradiated group, CA supplementation improved liver morphology, decreased serum alanine aminotransferase and aspartate aminotransferase, inhibited BCL2-associated X (BAX) protein expression, and improved the mice hematopoietic function. CA at the dose of 100 mg/kg body weight showed better effect compared to the other doses. Thus, CA might possess potential to protect against RILD.

Deficiency of Sirtuin 1 Impedes Endometrial Decidualization in Recurrent Implantation Failure Patients.

Decidualization is driven by differentiation of human endometrial stromal cells (ESCs), and is a prerequisite for successful implantation and establishment of pregnancy. The critical role of impaired decidualization in women suffered recurrent implantation failure (RIF) has been established, while the underlying mechanism is poorly understood. In the present study, we verified the essential role of Sirtuin1 (SIRT1) in regulating differentiation and maintaining reactive oxygen species (ROS) homeostasis of human ESCs during decidualization. The abundance of SIRT1 was decreased in RIF patients both in the endometria during window of implantation phase and in the decidualized ESCs. Downregulation of SIRT1 disrupted the intracellular ROS homeostasis during decidualization of ESC, manifested as the accumulation of intracellular ROS level and the reduction of antioxidant stress molecules. Elimination of ROS with N-acetyl-L-cysteine (NAC) could rescued the decidualization inhibition caused by SIRT1 knockdown. Further, we explored the insufficient expression of SIRT1 in ESC affected the deacetylation of forkhead box O1 (FOXO1), and thus inhibited the transcriptional activity of FOXO1. This could account for the dysregulation of intracellular ROS homeostasis during decidualization and decreased expression of decidual markers. Collectively, our findings provided insight into the role of down-regulated SIRT1 in the poor decidual response of ESCs in RIF patients.

Addressing the role of 11ß-hydroxysteroid dehydrogenase type 1 in the development of polycystic ovary syndrome and the putative therapeutic effects of its selective inhibition in a preclinical model.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common metabolic and endocrine disorder among reproductive-age women, and the leading cause of anovulatory infertility. 11ß-hydroxysteroid dehydrogenases-1 (11ß-HSD1) catalysing the conversion of inactive cortisone to active cortisol plays a crucial role in various metabolic diseases. However, whether 11ß-HSD1 is associated with the pathogenesis of PCOS and whether 11ß-HSD1 can be a treating target of PCOS remain unknown. METHODS: This study was first designed to explore the role of 11ß-HSD1 in PCOS development and the effect of selective 11ß-HSD1 inhibitor administration on PCOS treatment. Follicular fluid and granulosa cells (GCs) were collected from 32 non-PCOS patients and 37 patients with PCOS to measure cortisol and 11ß-HSDs levels. Female Sprague-Dawley rats (3-week-old) were injected with dehydroepiandrosterone (DHEA) to induce PCOS and their ovaries were collected to measure the abundance of corticosterone (CORT) and 11ß-HSDs. To determine the role of 11ß-HSD1 in PCOS development, we overexpressed 11ß-HSD1 in the ovaries of female rats (5-week-old) or knocked down the expression of 11ß-HSD1 in the ovaries from PCOS rats via lentivirus injection. After lentivirus infection, the body weights, ovarian weights, estrous cycles, reproductive hormones and morphology of the ovary were analysed in rats from different experimental groups. Then to figure out the translational potential of the selective 11ß-HSD1 inhibitor in treating PCOS, PCOS rats were treated with BVT.2733, a selective 11ß-HSD1 inhibitor and a cluster of PCOS-like traits were analysed, including insulin sensitivity, ovulatory function and fertility of rats from the Control, PCOS and PCOS+BVT groups. Rat ovarian explants and human GCs were used to explore the effect of CORT or cortisol on ovarian extracellular matrix remodelling. RESULTS: The elevated expression of 11ß-HSD1 contributed to the increased cortisol and corticosterone (CORT) concentrations observed in the ovaries of PCOS patients and PCOS rats respectively. Our results showed that ovarian overexpression of 11ß-HSD1 induced a cluster of PCOS phenotypes in rats including irregular estrous cycles, reproductive hormone dysfunction and polycystic ovaries. While knockdown of ovarian 11ß-HSD1 of PCOS rats reversed these PCOS-like changes. Additionally, the selective 11ß-HSD1 inhibitor BVT.2733 alleviated PCOS symptoms such as insulin resistance (IR), irregular estrous cycles, reproductive hormone dysfunction, polycystic ovaries, ovulatory dysfunction and subfertility. Moreover, we showed that cortisol target ovarian insulin signalling pathway and ovarian extracellular matrix (ECM) remodelling in vivo, in ovarian explants and in GCs. CONCLUSION: Elevated 11ß-HSD1 abundance in ovarian is involved in the pathogenesis of PCOS by impairing insulin signalling pathway and ECM remodelling. Selective inhibition of 11ß-HSD1 ameliorates a cluster of PCOS phenotypes. Our study demonstrates the selective 11ß-HSD1 inhibitor as a novel and promising strategy for the treatment of PCOS.

Metasurface-assisted massive backscatter wireless communication with commodity Wi-Fi signals.

Conventional wireless communication architecture, a backbone of our modern society, relies on actively generated carrier signals to transfer information, leading to important challenges including limited spectral resources and energy consumption. Backscatter communication systems, on the other hand, modulate an antenna's impedance to encode information into already existing waves but suffer from low data rates and a lack of information security. Here, we introduce the concept of massive backscatter communication which modulates the propagation environment of stray ambient waves with a programmable metasurface. The metasurface's large aperture and huge number of degrees of freedom enable unprecedented wave control and thereby secure and high-speed information transfer. Our prototype leveraging existing commodity 2.4 GHz Wi-Fi signals achieves data rates on the order of hundreds of Kbps. Our technique is applicable to all types of wave phenomena and provides a fundamentally new perspective on the role of metasurfaces in future wireless communication.

Intelligent Electromagnetic Sensing with Learnable Data Acquisition and Processing.

Electromagnetic (EM) sensing is a widespread contactless examination technique with applications in areas such as health care and the internet of things. Most conventional sensing systems lack intelligence, which not only results in expensive hardware and complicated computational algorithms but also poses important challenges for real-time in situ sensing. To address this shortcoming, we propose the concept of intelligent sensing by designing a programmable metasurface for data-driven learnable data acquisition and integrating it into a data-driven learnable data-processing pipeline. Thereby, a measurement strategy can be learned jointly with a matching data post-processing scheme, optimally tailored to the specific sensing hardware, task, and scene, allowing us to perform high-quality imaging and high-accuracy recognition with a remarkably reduced number of measurements. We report the first experimental demonstration of "learned sensing" applied to microwave imaging and gesture recognition. Our results pave the way for learned EM sensing with low latency and computational burden.

Intelligent metasurface imager and recognizer.

There is an increasing need to remotely monitor people in daily life using radio-frequency probe signals. However, conventional systems can hardly be deployed in real-world settings since they typically require objects to either deliberately cooperate or carry a wireless active device or identification tag. To accomplish complicated successive tasks using a single device in real time, we propose the simultaneous use of a smart metasurface imager and recognizer, empowered by a network of artificial neural networks (ANNs) for adaptively controlling data flow. Here, three ANNs are employed in an integrated hierarchy, transforming measured microwave data into images of the whole human body, classifying specifically designated spots (hand and chest) within the whole image, and recognizing human hand signs instantly at a Wi-Fi frequency of 2.4 GHz. Instantaneous in situ full-scene imaging and adaptive recognition of hand signs and vital signs of multiple non-cooperative people were experimentally demonstrated. We also show that the proposed intelligent metasurface system works well even when it is passively excited by stray Wi-Fi signals that ubiquitously exist in our daily lives. The reported strategy could open up a new avenue for future smart cities, smart homes, human-device interaction interfaces, health monitoring, and safety screening free of visual privacy issues.

The discordance pattern of molecular sub-types between primary and metastatic sites in Chinese breast cancer patients.

OBJECTIVE: Based on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER-2), and proliferation cell nuclear antigen (Ki-67) status, breast cancer (BC) can be divided into several molecular sub-types. The patterns of these biological receptors may change during the course of progression and metastasis which could lead to new treatment strategies accordingly. METHOD: The present multi-center-based clinical data investigated the discordance patterns of molecular features in Chinese BC patients between primary tumors and distant metastasis. 151 pathologically confirmed BC patients were enrolled. The comparison of the statuses of ER, PR, HER-2, and the Ki-67 index by the IHC and/or FISH method was performed. RESULTS: The discordance rate in one or more molecular markers was 52.4% and varied between primary and metastatic lesions. The most common transformation pattern was the loss of ER and PR. On the other hand, the ER-positive patients have the longest OS. Patients with ER changing from positive to negative have the shortest OS. The patients with PR changing from negative to positive have the longest OS, while PR-negative patients have the shortest OS. The median DFI (disease-free interval) was 54.93 months in this study. ER, PR, and HER-2 transformation rates are common in patients with DFI < 2 years than in patients with DFI ≥ 5 years. For patients with an ER-positive expression in metastatic lesions, a significantly prolonged PFS was observed (P < 0.05) in those receiving endocrine treatment. CONCLUSION: The transformation of molecular subtyping status was identified between primary and corresponding relapse lesions and was used for determining the treatment strategies and prognosis prediction in advanced BC patients.