Longitudinal Cervical Length Measurements and Spontaneous Preterm Birth in Singleton and Twin Pregnancies.

Importance: Changes in cervical length in twin pregnancies exhibit various patterns, but it is unclear whether the mechanism underlying spontaneous preterm birth (sPTB) is consistent. The existence of detailed phenomena in singleton pregnancies is also unclear. Objectives: To explore the different patterns in cervical length trajectories in singleton and twin pregnancies and to analyze whether the immunological mechanisms of sPTB are consistent among these cervical length patterns. Design, Setting, and Participants: This cohort study recruited pregnant individuals who received antenatal care and delivered at Peking University Third Hospital in Beijing, China, between January 1, 2014, and December 31, 2022. Individuals with singleton and twin pregnancies were included. Exposures: Cervical length measurements and white blood cell (WBC) indicators. Main Outcomes and Measures: The primary outcome was sPTB. Longitudinal trajectory cluster analysis was used to identify patterns of changes in cervical length in singleton and twin pregnancies. A random-effects model with cubic spline was used to fit and compare the longitudinal trajectory of WBC indicators among early preterm birth, moderate to late preterm birth, and term birth. Results: A total of 43 559 pregnant individuals were included; of these, 41 706 had singleton pregnancies (mean [SD)] maternal age, 33.0 [4.0] years) and 1853 had twin pregnancies (mean [SD] maternal age, 33.3 [3.6] years). Two distinct patterns of cervical length changes were observed in both singleton and twin pregnancies: shortened (21 366 singletons and 546 twins) and stable (20 340 singletons and 1307 twins). In singleton pregnancies, WBC count was associated with early sPTB in individuals with both shortened cervix (odds ratio [OR], 1.35; 95% CI, 1.00-1.82) and stable cervix (OR, 1.64; 95% CI, 1.07-2.50). However, for twin pregnancies, the association of WBC count (OR, 3.13; 95% CI, 1.58-6.18) with the risk of early sPTB was observed only in individuals with a shortened cervix. Conclusions and Relevance: This study identified 2 distinct cervical length patterns: shortened and stable. These patterns revealed 2 preterm birth mechanisms in twin pregnancies, with the immunopathogenesis of sPTB found only in the shortened cervix pattern; in singleton pregnancies, maternal immune response was associated with a higher risk of sPTB regardless of a shortened or stable cervix.

The changing Doppler patterns and perinatal outcomes of monochorionic diamniotic twins with selective fetal growth restriction.

OBJECTIVES: To investigate the clinical outcomes and Doppler patterns changes in monochorionic diamniotic (MCDA) twins with selective fetal growth restriction (sFGR). METHODS: We retrospectively analyzed 362 sFGR cases from January 2010 to May 2016 at a single tertiary referral center. The Doppler waveforms of umbilical artery end-diastolic flow were collected, and all neonates were subjected to an early neonatal brain scan. RESULTS: A total of 66/100 (66 %) type I cases were stable, whereas 25/100 (25 %) cases changed to type II and 9/100 (9 %) changed to sFGR complicated twin-twin transfusion syndrome (TTTS). A total of 48.9 % (22/45) sFGR cases were complicated with polyhydramnios and 30.4 % (7/23) sFGR cases were complicated with oligohydramnios, both of which were progressed to sFGR with TTTS. Mild cerebral injury was significantly associated with Doppler flow abnormalities, earlier gestational age at delivery and type of sFGR diagnosis. Severe cerebral injury was significantly associated with gestational age at delivery (31.6 vs. 34.1, p=0.002) and larger birthweight discordance (43.9 vs. 29.3 %, p=0.011). CONCLUSIONS: Doppler patterns in sFGR can gradually change, with important consequences with regard to management and outcomes. Along with abnormal Doppler findings, earlier occurrence of sFGR and delivery are associated with subsequent neonatal cerebral injury.

Serum lipid reference values recommended during a twin pregnancy and evaluating its association with perinatal outcomes.

BACKGROUND: Maternal lipid metabolism fluctuations have been shown to increase the risk of adverse pregnancy outcomes. However, there is no consensus over what constitutes normal maternal lipid values during twin pregnancy. Therefore, the aim of this study was to establish a serum lipid reference range for a twin pregnancy. METHODS: A retrospective survey was conducted, from 2011 to 2021, at the Peking University Third Hospital. A total of 881 twin pregnancies, with lipid data from early and middle pregnancies, were included. After excluding those with adverse pregnancy outcomes, we performed a descriptive analysis of total cholesterol (TC), triglycerides (TG), high-density lipid cholesterol (HDL-C), and low-density lipid cholesterol (LDL-C) levels, using the mean and standard deviation to determine appropriate percentiles. We later determined the lipid reference range in early and middle pregnancy based on the initial results. We evaluated Inappropriate lipid levels associations with pregnancy outcomes, including gestational diabetes, pregnancy-induced hypertension, small for gestational age. RESULTS: (1) Serum levels of TC, TG, LDL-C, and HDL-C increased significantly from early to late pregnancy, where the greatest increase was observed in TG. (2) Based on the results, we recommend that TC, TG, and LDL-C serum reference values during early and middle pregnancy should be less than the 95th percentile. On the other hand, HDL-C should be greater than the 5th percentile. During early pregnancy, the values recommended are TC < 5.31 mmol/L, TG < 2.25 mmol/L, HDL > 1.02 mmol/L and LDL < 3.27 mmol/L, and those during middle pregnancy are TC < 8.74 mmol/L, TG < 4.89 mmol/L, HDL > 1.25 mmol/L and LDL < 5.49 mmol/L, while the values during late pregnancy are TC < 9.11 mmol/L, TG < 6.70 mmol/L, HDL > 1.10 mmol/L and LDL < 5.81 mmol/L. Higher levels of blood lipids were associated with GDM, PE, SGA. CONCLUSIONS: We suggested a reference ranges for blood lipids during the twin pregnancy in a Chinese population. The reference ranges recommended by this study can be used to identify women with twin pregnancies using unfavorable lipid values. Higher levels of blood lipids were associated with adverse pregnancy outcomes.

A study on the correlation of placental anastomosis and superficial vascular branches of selective fetal growth restriction in monochorionic diamniotic twins.

INTRODUCTION: The main purpose of the present study was to investigate the correlation between placental anastomosis and superficial vascular branches in selective fetal growth restriction (sFGR) in monochorionic diamniotic twins. MATERIALS AND METHODS: This was a retrospective analysis of the pregnancy data and placental perfusion of 395 patients with monochorionic diamniotic (MCDA) twin pregnancies delivered at our hospital from April 2013 to April 2020. We divided the patients into two groups and compared the number of placental superficial vascular branches in sFGR twins and normal MCDA twins. The correlation between the placental anastomosis and the number of superficial vascular branches in sFGR and normal MCDA twins was also investigated. RESULTS: The number of umbilical arterial branches and umbilical venous branches was less than larger twins in sFGR, larger twins in normal MCDA and smaller twins in normal MCDA. (11.83 [4-44], 21.82 [7-50], 19.72 [3-38], 14.85 [0-31], p < 0.001, 6.08 [1-18], 9.60 [3-22], 9.96 [2-22], 8.38 [1-20], p < 0.00) For smaller twins in the sFGR group, the number of umbilical venous branches was positively associated with AA anastomosis overall diameter, AV anastomosis overall diameter and all anastomosis overall diameter. (r = 0.194, 0.182 and 0.211, p < 0.05) CONCLUSIONS: The risk of sFGR may arise when the placenta from MCDA twins shows a poor branching condition of placental superficial vessels. For the smaller twin of sFGR, regular ultrasound examination of the number of the umbilical venous branches may help to predict artery-to-artery (AA) overall diameter, artery-to-vein (AV) overall diameter and all anastomosis overall diameter.

Thick artery-artery anastomoses delay the onset of selective fetal growth restriction in monochorionic diamniotic twins: a 7-year single-center cohort study.

Objective: This study aimed to investigate differences in placental characteristics between early- and late-onset selective fetal growth restriction (sFGR) in monochorionic diamniotic twins. Methods: A total of 253 patients with sFGR between April 2013 and April 2020 were retrospectively analyzed. Placental characteristics of early- and late-onset sFGR were compared. Results: The gestational age at diagnosis and delivery in the early-onset group was significantly less than that in the late-onset group [22.0 (16.9-23.9) and 28.4 (24.0, 36.3) weeks, P < 0.001; 33.1 ± 2.2 and 33.7 ± 2.5 weeks, P = 0.025]. The birth weight of normal growth and growth-restricted fetuses in the early-onset group was less than the late-onset group [1,990 ± 422 and 2,162 ± 525 g, P = 0.044; 1,320 ± 409 and 1,595 ± 519 g, P = 0.001]. The birthweight discordance ratio in the early-onset group was greater than the late-onset group (0.34 ± 0.12 and 0.29 ± 0.13, P = 0.001). The early-onset group had a significantly lower prevalence of sFGR type I than the late-onset group (37.5 and 62.0%, P = 0.018). The early-onset group had a significantly higher prevalence of sFGR type III than the late-onset group (30.4 and 12.7%, P = 0.048). The early-onset group had a lower prevalence of thick artery-artery anastomoses than the late-onset group (37.5 and 62.0%, P = 0.006). The placental territory discordance ratio in the early-onset group was higher than in the late-onset group [0.60 (0.01, 0.80) and 0.50 (0.01, 0.88), P = 0.018]. Conclusion: Unequal placental territory is the cause for most of the late-onset sFGR. Thick artery-artery anastomoses may delay the onset time of these cases of sFGR.

Outcomes of fetal reduction versus expectant management in dichorionic triamniotic triplets.

OBJECTIVE: To compare the outcomes of dichorionic triamniotic (DCTA) triplets who underwent fetal reduction (FR) to singletons or twins with those managed expectantly. METHODS: We conducted a retrospective study of DCTA triplets with three living fetuses at 11-14 weeks over a 7-year period. Pregnancy outcomes were compared following different management strategies. RESULTS: Of 108 included patients, 22 underwent expectant management (EM), 28 were reduced to dichorionic diamniotic twins, and 58 to singletons. The median gestational age at birth for EM, FR to twins, and singletons was 33.1 weeks, 37.0 weeks, and 38.6 weeks, respectively (P < 0.001). Prematurity before 37 and 34 weeks was less common following FR to singletons and twins than in ongoing triplets (18.9%, 46.2% and 90.5%, P < 0.001; 13.2%, 26.9% and 57.1%, P < 0.001). Neonatal birth weight was higher in triplets reduced to singletons and twins compared with EM cases (3140g, 2315g, and 1860g, P < 0.001). However, rates of miscarriage, pregnancies with ≥1 survivor, maternal complications, and adverse neonatal outcomes were comparable among the three groups. CONCLUSIONS: In our experience, FR in DCTA triplets could reduce prematurity risk compared to EM, but it confers no survival advantage. Fetal reduction to singletons may result in more favorable outcomes than those reduced to dichorionic twins.

Soft, flexible pressure sensors for pressure monitoring under large hydrostatic pressure and harsh ocean environments.

Traditional rigid ocean pressure sensors typically require protection from bulky pressure chambers and complex seals to survive the large hydrostatic pressure and harsh ocean environment. Here, we introduce soft, flexible pressure sensors that can eliminate such a need and measure a wide range of hydrostatic pressures (0.1 MPa to 15 MPa) in environments that mimic the ocean, achieving small size, high flexibility, and potentially low power consumption. The sensors are fabricated from lithographically patterned gold thin films (100 nm thick) encapsulated with a soft Parylene C film and tested in a customized pressure vessel under well-controlled pressure and temperature conditions. Using a rectangular pressure sensor as an example, the resistance of the sensor is found to decrease linearly with the increase of the hydrostatic pressure from 0.1 MPa to 15 MPa. Finite element analysis (FEA) reveals the strain distributions in the pressure sensor under hydrostatic pressures of up to 15 MPa. The effect of geometry on sensor performance is also studied, and radially symmetric pressure sensors (like circular and spike-shaped) are shown to have more uniform strain distributions under large hydrostatic pressures and, therefore, have a potentially enhanced pressure measurement range. Pressure sensors of all geometries show high consistency and negligible hysteresis over 15 cyclic tests. In addition, the sensors exhibit excellent flexibility and operate reliably under a hydrostatic pressure of 10 MPa for up to 70 days. The developed soft pressure sensors are promising for integration with many platforms including animal tags, diver equipment, and soft underwater robotics.

Soft, flexible conductivity sensors for ocean salinity monitoring.

Flexible electrochemical sensors that measure the concentrations of specific analytes (e.g., ions, molecules, and microorganisms) provide valuable information for medical diagnosis, personal health care, and environmental monitoring. However, the conductive electrodes of such sensors need to be exposed to the surrounding environments like chloride-containing aqueous solutions during their operation, where chloride ions (Cl-) can potentially cause corrosion and dissolution of the sensors, negatively impacting their performance and durability. In this work, we develop soft, flexible conductivity sensors made of gold (Au) electrodes and systematically study their electrochemical behaviors in sodium chloride (NaCl) solutions to prevent chloride-induced corrosion and enhance their sensitivity for marine environmental monitoring. The causes of gold chlorination reactions and polarization effects are identified and effectively prevented by analyzing the effects of direct current (DC) and alternating current (AC) voltages, AC frequencies, and exposed sensing areas of the conductivity (salinity) sensors. Accordingly, a performance diagram is constructed to provide guidance for the selection of operation parameters for the salinity sensor. We also convert the varying impedance values of salinity sensors at different salinity levels into output voltage signals using a voltage divider circuit with an AC voltage (0.6 V) source. The results offer an assessment of the accuracy and response time of the salinity sensors, as well as their potential for integration with data transmission components for real-time ocean monitoring. This study has important implications for the development of soft, flexible, Au-based electrochemical sensors that can operate efficiently in diverse biological fluids and marine environments.

The role of E3 ubiquitin ligases and deubiquitinases in bladder cancer development and immunotherapy.

Bladder cancer is one of the common malignant urothelial tumors. Post-translational modification (PTMs), including ubiquitination, acetylation, methylation, and phosphorylation, have been revealed to participate in bladder cancer initiation and progression. Ubiquitination is the common PTM, which is conducted by E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating enzyme and E3 ubiquitin-protein ligase. E3 ubiquitin ligases play a key role in bladder oncogenesis and progression and drug resistance in bladder cancer. Therefore, in this review, we summarize current knowledge regarding the functions of E3 ubiquitin ligases in bladder cancer development. Moreover, we provide the evidence of E3 ubiquitin ligases in regulation of immunotherapy in bladder cancer. Furthermore, we mention the multiple compounds that target E3 ubiquitin ligases to improve the therapy efficacy of bladder cancer. We hope our review can stimulate researchers and clinicians to investigate whether and how targeting E3 ubiquitin ligases acts a novel strategy for bladder cancer therapy.

Nanoparticles overcome adaptive immune resistance and enhance immunotherapy via targeting tumor microenvironment in lung cancer.

Lung cancer is one of the common malignant cancers worldwide. Immune checkpoint inhibitor (ICI) therapy has improved survival of lung cancer patients. However, ICI therapy leads to adaptive immune resistance and displays resistance to PD-1/PD-L1 blockade in lung cancer, leading to less immune response of lung cancer patients. Tumor microenvironment (TME) is an integral tumor microenvironment, which is involved in immunotherapy resistance. Nanomedicine has been used to enhance the immunotherapy in lung cancer. In this review article, we described the association between TME and immunotherapy in lung cancer. We also highlighted the importance of TME in immunotherapy in lung cancer. Moreover, we discussed how nanoparticles are involved in regulation of TME to improve the efficacy of immunotherapy, including Nanomedicine SGT-53, AZD1080, Nanomodulator NRF2, Cisplatin nanoparticles, Au@PG, DPAICP@ME, SPIO NP@M-P, NBTXR3 nanoparticles, ARAC nanoparticles, Nano-DOX, MS NPs, Nab-paclitaxel, GNPs-hPD-L1 siRNA. Furthermore, we concluded that targeting TME by nanoparticles could be helpful to overcome resistance to PD-1/PD-L1 blockade in lung cancer.

Inflammatory Response and Exosome Biogenesis of Choroid Plexus Organoids Derived from Human Pluripotent Stem Cells.

The choroid plexus (ChP) is a complex structure in the human brain that is responsible for the secretion of cerebrospinal fluid (CSF) and forming the blood-CSF barrier (B-CSF-B). Human-induced pluripotent stem cells (hiPSCs) have shown promising results in the formation of brain organoids in vitro; however, very few studies to date have generated ChP organoids. In particular, no study has assessed the inflammatory response and the extracellular vesicle (EV) biogenesis of hiPSC-derived ChP organoids. In this study, the impacts of Wnt signaling on the inflammatory response and EV biogenesis of ChP organoids derived from hiPSCs was investigated. During days 10-15, bone morphogenetic protein 4 was added along with (+/-) CHIR99021 (CHIR, a small molecule GSK-3ß inhibitor that acts as a Wnt agonist). At day 30, the ChP organoids were characterized by immunocytochemistry and flow cytometry for TTR (~72%) and CLIC6 (~20%) expression. Compared to the -CHIR group, the +CHIR group showed an upregulation of 6 out of 10 tested ChP genes, including CLIC6 (2-fold), PLEC (4-fold), PLTP (2-4-fold), DCN (~7-fold), DLK1 (2-4-fold), and AQP1 (1.4-fold), and a downregulation of TTR (0.1-fold), IGFBP7 (0.8-fold), MSX1 (0.4-fold), and LUM (0.2-0.4-fold). When exposed to amyloid beta 42 oligomers, the +CHIR group had a more sensitive response as evidenced by the upregulation of inflammation-related genes such as TNFα, IL-6, and MMP2/9 when compared to the -CHIR group. Developmentally, the EV biogenesis markers of ChP organoids showed an increase over time from day 19 to day 38. This study is significant in that it provides a model of the human B-CSF-B and ChP tissue for the purpose of drug screening and designing drug delivery systems to treat neurological disorders such as Alzheimer's disease and ischemic stroke.

The Proteome Landscape of Human Placentas for Monochorionic Twins with Selective Intrauterine Growth Restriction.

In perinatal medicine, intrauterine growth restriction (IUGR) is one of the greatest challenges. The etiology of IUGR is multifactorial, but most cases are thought to arise from placental insufficiency. However, identifying the placental cause of IUGR can be difficult due to numerous confounding factors. Selective IUGR (sIUGR) would be a good model to investigate how impaired placentation affects fetal development, as the growth discordance between monochorionic twins cannot be explained by confounding genetic or maternal factors. Herein, we constructed and analyzed the placental proteomic profiles of IUGR twins and normal cotwins. Specifically, we identified a total of 5481 proteins, of which 233 were differentially expressed (57 up-regulated and 176 down-regulated) in IUGR twins. Bioinformatics analysis indicates that these differentially expressed proteins (DEPs) are mainly associated with cardiovascular system development and function, organismal survival, and organismal development. Notably, 34 DEPs are significantly enriched in angiogenesis, and diminished placental angiogenesis in IUGR twins has been further elaborately confirmed. Moreover, we found decreased expression of metadherin (MTDH) in the placentas of IUGR twins and demonstrated that MTDH contributes to placental angiogenesis and fetal growth in vitro. Collectively, our findings reveal the comprehensive proteomic signatures of placentas for sIUGR twins, and the DEPs identified may provide in-depth insights into the pathogenesis of placental dysfunction and subsequent impaired fetal growth.

Research progress of neoantigen-based dendritic cell vaccines in pancreatic cancer.

The mutation of the crucial genes such as tumor suppressors or oncogenes plays an important role in the initiation and development of tumors. The non-synonymous mutations in the tumor cell genome will produce non-autologous proteins (neoantigen) to activate the immune system by activating CD4+ and CD8+ T cells. Neoantigen-based peptide vaccines have exhibited exciting therapeutic effects in treating various cancers alone or in combination with other therapeutic strategies. Furthermore, antigen-loaded DC vaccines are more powerful in inducing stronger immune responses than vaccines generated by antigens and adjuvants. Therefore, neoantigen-based dendritic cell (DC) vaccines could achieve promising effects in combating some malignant tumors. In this review, we summarized and discussed the recent research progresses of the neoantigen, neoantigen-based vaccines, and DC-based vaccine in pancreatic cancers (PCs). The combination of the neoantigen and DC-based vaccine in PC was also highlighted. Therefore, our work will provide more detailed evidence and novel opinions to promote the development of a personalized neoantigen-based DC vaccine for PC.

Covalently Attached Slippery Surface Coatings to Reduce Protein Adsorptions on Poly(dimethylsiloxane) Planar Surfaces and 3D Microfluidic Channels.

Silicone elastomers, such as poly(dimethylsiloxane) (PDMS), have a broad range of applications in basic biomedical research and clinical medicine, ranging from the preparation of microfluidic devices for organs-on-chips and ventriculoperitoneal shunts for the treatment of hydrocephalus to implantable neural probes for neuropharmacology. Despite the importance, the protein adsorptions on silicone elastomers in these application environments represent a significant challenge. Surface coatings with slippery lubricants, inspired by the Nepenthes pitcher plants, have recently received much attention for reducing protein adsorptions. Nevertheless, the depletion of the physically infused lubricants limits their broad applications. In this study, we report a covalently attached slippery surface coating to reduce protein adsorptions on PDMS surfaces. As demonstrations, we show that the adsorption of serum proteins, human fibrinogen and albumin, can be significantly reduced by the slippery surface coating in both planar PDMS surfaces and 3D microfluidic channels. The preparation of slippery surface coatings relies on the acid-catalyzed polycondensation reaction of dimethyldimethoxysilane, which utilizes a low-cost and scalable dip-coating method. Furthermore, cell metabolic activity and viability studies demonstrate the biocompatibility of the surface coating. These results suggest the potential applications of slippery surface coatings to reduce protein adsorptions for implantable medical devices, organs-on-chips, and many others.

Biosensor integrated tissue chips and their applications on Earth and in space.

The development of space exploration technologies has positively impacted everyday life on Earth in terms of communication, environmental, social, and economic perspectives. The human body constantly fluctuates during spaceflight, even for a short-term mission. Unfortunately, technology is evolving faster than humans' ability to adapt, and many therapeutics entering clinical trials fail even after being subjected to vigorous in vivo testing due to toxicity and lack of efficacy. Therefore, tissue chips (also mentioned as organ-on-a-chip) with biosensors are being developed to compensate for the lack of relevant models to help improve the drug development process. There has been a push to monitor cell and tissue functions, based on their biological signals and utilize the integration of biosensors into tissue chips in space to monitor and assess cell microenvironment in real-time. With the collaboration between the Center for the Advancement of Science in Space (CASIS), the National Aeronautics and Space Administration (NASA) and other partners, they are providing the opportunities to study the effects of microgravity environment has on the human body. Institutions such as the National Institute of Health (NIH) and National Science Foundation (NSF) are partnering with CASIS and NASA to utilize tissue chips onboard the International Space Station (ISS). This article reviews the endless benefits of space technology, the development of integrated biosensors in tissue chips and their applications to better understand human biology, physiology, and diseases in space and on Earth, followed by future perspectives of tissue chip applications on Earth and in space.

Progress of radiological­pathological workflows in the differential diagnosis between primary central nervous system lymphoma and high­grade glioma (Review).

Primary central nervous system lymphoma (PCNSL) and high­grade glioma (HGG) are distinct entities of the CNS with completely distinct treatments. The treatment of PCNSL is chemotherapy­based, while surgery is the first choice for HGG. However, the clinical features of the two entities often overlap, and a clear pathological diagnosis is important for subsequent management, especially for the management of PCNSL. Stereotactic biopsy is recognized as one of the minimally invasive alternatives for evaluating the involvement of the CNS. However, in the case of limited tissue materials, the differential diagnosis between the two entities is still difficult. In addition, some patients are too ill to tolerate a needle biopsy. Therefore, combining imaging, histopathology and laboratory examinations is essential in order to make a clear diagnosis as soon as possible. The present study reviews the progress of comparative research on both imaging and laboratory tests based on the pathophysiological changes of the two entities, and proposes an integrative and optimized diagnostic process, with the purpose of building a better understanding for neurologists, hematologists, radiologists and pathologists.

Studying the Inflammatory Responses to Amyloid Beta Oligomers in Brain-Specific Pericyte and Endothelial Co-culture from Human Stem Cells.

Background: Recently, the in vitro blood brain barrier (BBB) models derived from human pluripotent stem cells have been given extensive attention in therapeutics due to the implications it has with the health of the central nervous system. It is essential to create an accurate BBB model in vitro in order to better understand the properties of the BBB and how it can respond to inflammatory stimulation and be passed by targeted or non-targeted cell therapeutics, more specifically extracellular vesicles. Methods: Brain-specific pericytes (iPCs) were differentiated from iPSK3 cells using dual SMAD signaling inhibitors and Wnt activation plus fibroblast growth factor 2 (FGF-2). The derived cells were characterized by immunostaining, flow cytometry and RT-PCR. In parallel, blood vessels organoids were derived using Wnt activation, BMP4, FGF2, VEGF and SB431542. The organoids were replated and treated with retinoic acid to enhance the blood brain barrier (BBB) features in the differentiated brain endothelial cells (iECs). Co-culture was performed for the iPCs and iECs in transwell system and 3-D microfluidics channels. Results: The derived iPCs expressed common markers PDGFRb and NG2, as well as brain-specific genes FOXF2, ABCC9, KCNJ8, and ZIC1. The derived iECs expressed common endothelial cell markers CD31, VE-cadherin, as well as BBB-associated genes BRCP, GLUT-1, PGP, ABCC1, OCLN, SLC2A1. The co-culture of the two cell types responded to the stimulation of amyloid ß42 oligomers by the upregulation of expression of TNFa, IL6, NFKB, Casp3, SOD2 and TP53. The co-culture also showed the property of trans-endothelial electrical resistance. The proof-of-concept vascularization strategy was demonstrated in a 3-D microfluidics-based device. Conclusion: The derived iPCs and iECs have brain-specific properties and the co-culture of iPCs and iECs provides an in vitro BBB model that show inflammatory response. This study has significance in establishing micro-physiological systems for neurological disease modeling and drug screening.

Effect of fetoscopic laser surgery on the placental characteristics and birth-weight discordance of twins with twin-to-twin transfusion syndrome.

Objective: This study explored the effect of fetoscopic laser surgery on the placental structure and birth-weight discordance of twin-to-twin transfusion syndrome (TTTS). Methods: A retrospective cohort study was conducted in TTTS patients who were admitted to the Peking University Third Hospital between April 2014 and April 2020. The patients were divided into two groups: laser group and control group. Placentas with twin survival were injected, and pregnancy outcomes and placental characteristics of the two groups were compared. The correlation between the birth-weight discordance and placental characteristics in each group was analyzed. Results: The gestational age at first diagnosis in the laser group was significantly smaller than that in the control group (21.6 ± 2.8 weeks vs. 27.7 ± 3.0 weeks, p < 0.001). The proportion of patients with TTTS stage-I in the laser group was significantly lower than the control group (9.4 vs. 64.0%, p < 0.001). The gestational age at delivery in the laser group was significantly larger than that in the control group (33.6 ± 2.1 weeks vs. 31.4 ± 2.5 weeks, p = 0.001). In the laser group, the birth-weight discordance ratio was positively correlated with the placental territory discordance ratio (Spearman coefficient = 0.556; p = 0.001). Conclusion: The birth-weight discordance is positively correlated with placental territory discordance in TTTS patients after FLS.

Three-dimensional thermochromic liquid crystal elastomer structures with reversible shape-morphing and color-changing capabilities for soft robotics.

Functional structures with reversible shape-morphing and color-changing capabilities are promising for applications including soft robotics and biomimetic camouflage devices. Despite extensive studies, there are few reports on achieving both reversible shape-switching and color-changing capabilities within one structure. Here, we report a facile and versatile strategy to realize such capabilities via spatially programmed liquid crystal elastomer (LCE) structures incorporated with thermochromic dyes. By coupling the shape-changing behavior of LCEs resulting from the nematic-to-isotropic transition of liquid crystals with the color-changing thermochromic dyes, 3D thermochromic LCE structures change their shapes and colors simultaneously, which are controlled by the nematic-isotropic transition temperature of LCEs and the critical color-changing temperature of dyes, respectively. Demonstrations, including the simulated blooming process of a resembled flower, the camouflage behavior of a "butterfly"/"chameleon" robot in response to environmental changes, and the underwater camouflage of an "octopus" robot, highlight the reliability of this strategy. Furthermore, integrating micro-ferromagnetic particles into the "octopus" thermochromic LCE robot allows it to respond to thermal-magnetic dual stimuli for "adaptive" motion and diverse biomimetic motion modes, including swimming, rolling, rotating, and crawling, accompanied by color-changing behaviors for camouflage. The reversibly reconfigurable and color-changing thermochromic LCE structures are promising for applications including soft camouflage robots and multifunctional biomimetic devices.

Soft, Pressure-Tolerant, Flexible Electronic Sensors for Sensing under Harsh Environments.

Energy-efficient, miniaturized electronic ocean sensors for monitoring and recording various environmental parameters remain a challenge because conventional ocean sensors require high-pressure chambers and seals to survive the large hydrostatic pressure and harsh ocean environment, which usually entail a high-power supply and large size of the sensor system. Herein, we introduce soft, pressure-tolerant, flexible electronic sensors that can operate under large hydrostatic pressure and salinity environments, thereby eliminating the need for pressure chambers and reducing the power consumption and sensor size. Using resistive temperature and conductivity (salinity) sensors as an example for demonstration, the soft sensors are made of lithographically patterned metal thin films (100 nm) encapsulated with soft oil-infused elastomers and tested in a customized pressure vessel with well-controlled pressure and temperature conditions. The resistance of the temperature and pressure sensors increases linearly with a temperature range of 5-38 °C and salinity levels of 30-40 Practical Salinity Unit (PSU), respectively, relevant for this application. Pressure (up to 15 MPa) has shown a negligible effect on the performance of the temperature and salinity sensors, demonstrating their large pressure-tolerance capability. In addition, both temperature and salinity sensors have exhibited excellent cyclic loading behaviors with negligible hysteresis. Encapsulated with our developed soft oil-infused elastomer (PDMS, poly(dimethylsiloxane)), the sensor has shown excellent performance under a 35 PSU salinity water environment for more than 7 months. The soft, pressure-tolerant and noninvasive electronic sensors reported here are suitable for integration with many platforms including animal tags, profiling floats, diving equipment, and physiological monitoring.