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Abstract Three-dimensional Spatial Transcriptomics has revolutionized our understanding of tissue regionalization, organogenesis, and development. However, existing approaches overlook either spatial information or experiment-induced distortions, leading to significant discrepancies between reconstruction results and in vivo cell locations, causing unreliable downstream analysis. To address these challenges, we propose ST-GEARS (Spatial Transcriptomics GEospatial profile recovery system through AnchoRS). By employing innovative Distributive Constraints into the Optimization scheme, ST-GEARS retrieves anchors with exceeding precision that connect closest spots across sections in vivo. Guided by the anchors, it first rigidly aligns sections, next solves and denoises Elastic Fields to counteract distortions. Through mathematically proved Bi-sectional Fields Application, it eventually recovers the original spatial profile. Studying ST-GEARS across number of sections, sectional distances and sequencing platforms, we observed its outstanding performance on tissue, cell, and gene levels. ST-GEARS provides precise and well-explainable ‘gears’ between in vivo situations and in vitro analysis, powerfully fueling potential of biological discoveries.

Abstract Currently, there is a lack of relevant research on the efficacy difference between SHD combined with IBG and PVIBGT in the treatment of osteonecrosis of the femoral head(ONFH). Firstly, this study intends to compare the effectiveness of surgical hip dislocation combined with impacting bone grafts (SHD-IBG) and pedicled vascularised iliac bone graft transfer (PVIBGT) in treating ONFH. And the study investigates patients who suffered from hip preservation failures from both groups to better comprehend failure reasons. 30 patients (34 hips) with ARCO stage IIIA femoral head necrosis were selected between January 2012 and July 2022. They were divided into group A(SHD-IBG) and group B (PVIBGT) according to different surgical methods. Firstly, compared the 1-year effect between SHD-IBG and PVIBGT at 1 year postoperatively; Secondly, assessed the medium and long-term efficacy of SHD-IBG hip preservation treatment; Lastly, based on study of the femoral head removed from patients with hip preservation failure in the two groups, the reasons for the failure of hip preservation were comprehensively analyzed in the two groups. Group A: 11 males (13 hips), 4 females (4 hips);Group B: 9 males (11 hips), 6 females (6 hips).Firstly, the average Harris scores of the two groups at 1 year after surgery: preoperative: 70.7, 1 year after surgery: 78.9 in group A; preoperative: 69.5, 1 year after surgery: 81.5 in group B. The differences were statistically significant (P

Ti6Al4V lattice structures (LSs) have great potentials in medical implants due to their excellent biocompatibility and high strength-to-weight ratio. This paper investigates the manufacturability and performance of unique Ti6Al4V heterogeneous glass sponge (GS) LSs fabricated via laser powder bed fusion (LPBF). Compared with the commonly used LSs, including Cross, body-centered cubic (BCC), Diamond and octet-truss (OCT), Ti6Al4V GS LSs exhibit the strongest compressive strength and energy absorption ability of 58 MPa and 23.84 J/cm3, respectively. Finite element (FE) models are established to evaluate the macroscopic deformation, microscopic stress and strain evolution in the solid struts of five different LSs. Local plastic stresses are found to generate near the nodes of Cross, BCC, Diamond and OCT LSs, thus forming plastic hinges, while the GS LSs can evenly transfer local plastic stresses to the grid-like rods of each layer, eventually showing a uniform stress distribution. Moreover, all the LSs are featured with satisfactory biocompatibility concerning cytotoxicity, cell proliferation, and cell attachment. The results indicate that the Ti6Al4V GS LSs can address the conflict between lightness and strength simultaneously, thus achieving excellent energy absorption performance, compressive properties and great biocompatibility, endowing it with tremendous application potential in the field of medical implants.

This paper focuses on daily freight train scheduling and dynamic railcar routing problems for rail freight transportation at the operational level. Two mixed integer linear programming models that adopted different strategies were formulated based on a continuous two-layer time-space network. We simultaneously considered the benefits of railroad company and service quality when setting the objective function. By solving the models, we can distribute the dynamic railcar flows to the train paths in the basic train timetable to obtain the daily train operation plan over a short time horizon (e.g. a day), which will be helpful for dispatchers to make decisions such as the empty railcar distribution and car routing (trip planning). Finally, we compared two models on a part of the Chinese railroad network. The results show that the second model can effectively improve the efficiency of railroad freight transportation.

How to precisely modulate the morphology and distribution of precipitated phases to have long-term antibacterial activity and outstanding strength-ductility has slowed the overall development and engineering applications of Cu-bearing biomedical titanium alloys. For the first time, the electron beam powder bed fusion (EBPBF) was employed to design titanium alloys with a completely solid solution, and containing fine Ti2Cu precipitates in both uniform and layered structures. The mechanical properties of the designed alloy with the layered (α-Ti and Ti2Cu) structure are superior to the other structures, especially with an outstanding compressive yield strength of 1221.9 MPa. Simultaneously, the wear resistance of the heterogeneous structures containing Ti2Cu precipitates was significantly improved, with a specific wear rate only half of that of the EBPBF-fabricated Ti6Al4V alloy. The compact arrangement of Ti2Cu phases created a large number of interfaces conducive to the formation of corrosion channels, which provided the capacity of continuous Cu2+ release. This work comprehensively analyzes the effects of heterogeneous structures on enhancing the sustained antibacterial capacity and optimizing the mechanical properties of a Cu-containing titanium alloy, laying a good foundation for their application in clinical and implantable devices.

Abstract Perovskite-type lead-free piezoelectric ceramics allow access to illustrious piezoelectric coefficients (d 33) through intricate composition design and experimental modulation. Developing a swift and accurate technology for identifying (K, Na)NbO3 (KNN)-based ceramic compositions with high d 33 in exceedingly large “compositional” space will establish an innovative research paradigm surpassing the traditional empirical trial-and-error method. Herein, we demonstrate an interpretable machine learning (ML) framework for quick evaluation of KNN-based ceramics with high d 33 based on data from published literature. Specifically, a thorough feature construction was carried out from the global and local dimensions to establish tree regression models with d 33 as the target property. Subsequently, the feature-property mapping rules of KNN-based piezoelectric ceramics are further optimized through feature screening. To intuitively understand the correlation mechanisms between ML regression targets and features, the sure independence screening and sparsifying operator (SISSO) method was employed to extract the essential descriptors to explain d 33. A straightforward descriptor, $${\text{e}}^{({{NM}}_{\text{B}}-{{MV}}_{\text{B}})}\cdot {ST}/{(I{D}_{\text{A}})}^{2}$$ e ( NM B − MV B ) ⋅ ST / ( I D A ) 2 , consisting of only four easily accessible parameters, can accelerate the evaluation of a series of novel KNN-based ceramics with high d 33 while exhibiting strong theoretical interpretability. This work not only provides a tool for the rapid discovery of high piezoelectric performance in KNN-based ceramics but also offers a data-driven route for the design of property descriptors in perovskites.

The initial triggering mechanism of nitromethane is investigated by first-principles molecular dynamics simulations and temperature-dependent Raman spectroscopy experiment. The Raman spectra at different temperature are obtained by Car-Parrinello molecular dynamics simulation to explore the activated vibration modes caused by low-temperature heat. The temperature-dependent Raman spectra experiment is constructed to compare with the theoretical data. Each possible initial reaction path caused by the activated vibration mode is analyzed to reveal the triggering mechanism of the initial chemical bond breaking for nitromethane. The results show that the intermolecular double-proton transfer is the first reaction step which is triggered by the intermolecular hydrogen bond reinforced with the active C–H stretching vibration (near 3000 cm−1), which is not reported before. The scanning energy barrier related to the increase of C–H bond lengths is about 60 kcal/mol, which is consistent with the calculated activation barrier (59.8 kcal/mol) of intermolecular proton transfer reaction. This proves the reliability of our conclusions. The results provide a new interpretation for the long-debated initial decomposition mechanism of nitromethane.

Fish in nature can extract the vortex energies from the environment to enhance their swimming performance. This paper numerically investigated the hydrodynamic characteristics and the energy-saving advantages of an undulating fish-like body behind the vortical flows generated by an upstream cylinder. The numerical model was based on a robust ghost cell immersed boundary method for the solution of incompressible flows around arbitrary complex flexible boundaries. We examined the dynamic characteristics, the swimming performance, and the wake structures of the downstream fish under different locations and diameters of the cylinder in a wide range of Strouhal numbers. It was found that the average drag coefficient was significantly reduced in the presence of the upstream cylinder, while the RMS (root mean square) lift coefficients were very close for different locations and diameters of the cylinder as well as in the fish-only case. Therefore, the downstream fish gain efficiency and thrust enhancement by capturing energies from the vortex flows, which are more significant for smaller Strouhal numbers (St). However, the swimming efficiency converges to near 0.12 at St = 1.2 for different locations and diameters of the upstream cylinder, just slightly higher than that of the fish-only case. The fish can experience the thrust in not only the von-Kármán vortex street, but also the reversed one. In addition, the fish can be situated in the extended shear layer region and the fully developed wake region dependent on the position and diameter of the upstream cylinder, leading to abundant wake modes such as the splitting, coalescing, and competing of vortices.

Based on the recent experiments on the triangular lattice antiferromagnet Na_{2}BaCo(PO_{4})_{2}, we propose the easy-axis XXZ spin-1/2 model on the triangular lattice, that exhibits a quantum spin supersolid, to be a precursory Dirac spin liquid. Despite the presence of a three-sublattice magnetic order as a spin supersolid, we suggest that this system is close to a Dirac spin liquid by exploring its spectroscopic response. The physical consequence is examined from the spectroscopic response, and we establish the continuous spectra near the M point in addition to the K point excitation from the spinon continuum on top of the three-sublattice order. Moreover, the satellite peaks were predicted at the mid-points connecting the Γ and K points. This proposal offers a plausible understanding of the recent inelastic neutron scattering measurement in Na_{2}BaCo(PO_{4})_{2} and could inspire further research in relevant models and materials, such as K_{2}Co(SeO_{3})_{2} and Rb_{2}Co(SeO_{3})_{2}, and even more anisotropic magnets like PrMgAl_{11}O_{19}.

Motivated by the recent experiments and the wide tunability on the MoTe_{2}/WSe_{2} moiré heterobilayer, we consider a physical model to explore the underlying physics for the interplay between the itinerant carriers and the local magnetic moments. In the regime where the MoTe_{2} is tuned to a triangular lattice Mott insulator and the WSe_{2} layer is doped with the itinerant holes, we invoke the itinerant ferromagnetism from the double-exchange mechanism for the itinerant holes on the WSe_{2} layer and the local moments on the MoTe_{2} layer. Together with the antiferromagnetic exchange on the MoTe_{2} layer, the itinerant ferromagnetism generates the scalar spin chirality distribution in the system. We further point out the presence of spin-assisted hopping in addition to the Kondo coupling between the local spin and the itinerant holes, and demonstrate the topological Hall effect for the itinerant holes in the presence of the noncollinear spin configurations. This work may improve our understanding of the correlated moiré systems and inspire further experimental efforts.

This paper addresses the problem of fault detection in DC microgrids in the presence of denial-of-service (DoS) attacks. To deal with the nonlinear term in DC microgrids, a Takagi-Sugeno (T-S) model is employed. In contrast to the conventional approach of utilizing current sampling data in the traditional event-triggered mechanism (ETM), a novel integrated ETM employs historical information from measured data. This innovative strategy mitigates the generation of additional triggering packets resulting from random perturbations, thus reducing redundant transmission data. Under the assumption of faults occurring within a finite-frequency domain, a resilient event-based H−/H∞ fault detection filter (FDF) is designed to withstand DoS attacks. The exponential stability conditions are derived in the form of linear matrix inequalities to ensure the performance of fault detected systems. Finally, the simulation results are presented, demonstrating that the designed FDF effectively detects finite-frequency faults in time even under DoS attacks. Furthermore, the FDF exhibits superior fault detection sensitivity compared to the conventional H∞ method, thus confirming the efficacy of the proposed approach. Additionally, it is observed that a trade-off exists between fault detection performance and the data releasing rate (DRR).

The gas turbine is a crucial piece of equipment in the energy and power industry. The exhaust gas has a sufficiently high temperature to be recovered for energy cascade use. The supercritical carbon dioxide (S-CO2) Brayton cycle is an advanced power system that offers benefits in terms of efficiency, volume, and flexibility. It may be utilized for waste heat recovery (WHR) in gas turbines. This study involved the design of a 5 MW S-CO2 recompression cycle specifically for the purpose of operational control. The dynamic models for the printed circuit heat exchangers, compressors, and turbines were developed. The stability and dynamic behavior of the components were validated. The suggested control strategies entail utilizing the cooling water controller to maintain the compressor inlet temperature above the critical temperature of CO2 (304.13 K). Additionally, the circulating mass flow rate is regulated to modify the output power, while the exhaust gas flow rate is controlled to ensure that the turbine inlet temperature remains within safe limits. The simulations compare the performance of PI controllers tuned using the SIMC rule and ADRC controllers tuned using the bandwidth method. The findings demonstrated that both controllers are capable of adjusting operating conditions and effectively suppressing fluctuations in the exhaust gas. The ADRC controllers exhibit a superior control performance, resulting in a 55% reduction in settling time under the load-tracking scenario.

Silkie chicken, an important chicken breed with high medicinal and nutritional value, has a long history of being used as a dietary supplement in China. However, the compounds with health-promoting effects in Silkie chickens remain unclear. In the present study, we conducted a comprehensive analysis of metabolic and lipidomic profiles to identify the characteristic bioactive compounds in Silkie chickens, using a common chicken breed as control. The results showed that the levels of 13 metabolites including estradiol, four lipid subclasses including cardiolipin (CL), eight lipid molecules, and three fatty acids including docosahexaenoic acid (C22:6) were significantly increased in Silkie chickens, which have physiological activities such as resisting chronic diseases and improving cognition. These characteristic bioactive compounds have effects on meat quality characteristics, including improving its water-holding capacity and umami taste and increasing the content of aromatic compounds and phenols. The differentially expressed genes (DEGs) between the two chicken breeds revealed the regulatory network for these characteristic bioactive compounds. Fifteen DEGs, including HSD17B1, are involved in the synthesis of characteristic metabolites. Eleven DEGs, including ELOVL2, were involved in the synthesis and transport of characteristic lipids and fatty acids. In summary, we identified characteristic bioactive compounds in Silkie chickens, and analyzed their effects on meat quality characteristics. This study provided important insight into Silkie chicken meat as a functional food.

Abstract Cloud computing has emerged as a promising paradigm for meeting the growing resource demands of Internet of Things (IoT) devices. Meanwhile, with the popularity of mobile aerial base stations, Unmanned Aerial Vehicle (UAV) assisted cloud computing is essential for providing diversified service at areas without available infrastructure. However, it is difficult to meet the requirements of a number of IoT devices which distribute a large area through one single UAV cloud server, and thus multi-clouds have been applied in large-scale IoT environments. Due to the limited battery capacity of UAV, hybrid energy supply has been considered as an effective approach. How to allocate the computing resources and offload the tasks to the UAV-assisted clouds is a challenging task. In this paper, we study the trade-off between the energy consumption and system performance in a UAV-assisted multi-clouds system. Considering the transmission and execution cost, a dynamic optimization problem with the objective of minimizing the power consumption of UAVs with the constraint of queue stability is formulated, which is further decomposed into three sub-problems using stochastic optimization techniques. A collaborative task offloading and resources allocation algorithm (CTORAA) based on artificial intelligent (AI) technique is proposed to jointly determine task offloading and energy harvesting. We provide corresponding mathematical analysis showing that CTORAA can reach the arbitrary profit-stability trade-off. Finally, we conduct simulation experiments to validate the efficacy of our algorithm.

β-lactam antibiotics are the most frequently used drugs and the most common drugs that cause allergic reactions in pediatrics. The occurrence of some allergic reactions can be predicted by skin testing, especially severe adverse reactions such as anaphylactic shock. Thus, penicillin and cephalosporin skin tests are widely used to predict allergic reactions before medication in pediatrics. However, false-positive results from skin tests were more often encountered in pediatrics than in adults. In fact, many children labeled as allergic to β-lactam are not allergic to the antibiotic, leading to the use of alternative antibiotics, which are less effective and more toxic, and the increase of antibiotic resistance. There has been controversy over whether β-lactam antibiotics should be tested for skin allergies before application in children. Based on the great controversy in the implementation of β-lactam antibiotic skin tests, especially the controversial cephalosporin skin tests in pediatrics, the mechanism and reasons of anaphylaxis to β-lactam antibiotics, the significance of β-lactam antibiotic skin tests, the current state of β-lactam antibiotic skin tests at home and abroad, and the problems of domestic and international skin tests were analyzed to determine a unified standard of β-lactam antibiotic skin tests in pediatrics to prevent and decrease adverse drug reactions, avoid waste of drugs, and a large amount of manpower and material resource consumption.

As China's ecological civilization gains momentum and the ecological development of the ‘Yangtze River Economic Belt’ strategy pushes forward, the research on water environment protection and management in Wuhan Metropolitan Area (the central urban agglomeration) is of great significance. According to the data of the industrial wastewater discharge in the nine cities of the Wuhan Metropolitan Area from 2005 to 2015, the study will construct a decomposition model to analyze the pattern of the discharge with reference to the Kaya identity and the LMDI decomposition model. By doing so, the pattern and driving factors of industrial wastewater discharge can be cleared. The following conclusions on the industrial wastewater discharge of the Wuhan Metropolitan Area can be achieved. Firstly, industrial wastewater discharge in the Wuhan Metropolitan Area shows a decreasing trend year by year (684 million tons to 433 million tons) from 2005 to 2010, but rises sharply (504 million tons to 652 million tons) from 2010 to 2011, reaching a peak in 2011. After that, it witnesses a quick and stable drop. Secondly, the absolute differences in industrial wastewater discharge among cities are continuously narrowed, in which Wuhan (the highest value is 260 million tons, the lowest value is 155 million tons) and Ezhou (the highest value is 181 million tons, the lowest value is 0.25 million tons) show the most striking abnormal statistics. Thirdly, the discharge follows the trend of expansion from Wuhan as a center to its neighboring cities from 2005 to 2015. For spatial pattern, it presents a picture of decreasing from the center to the surrounding. Lastly, for all driving factors affecting the discharge, the contribution of economic growth is always positive, which can increase the discharge greatly (the average annual contribution reaches 0.64 billion m3). The population size has little effect. The industrial structure has an uncertain influence on it since it is decided by government policies. The influence of technological improvement is negative, which can control the discharge a lot. In the last part of this essay, the research will explore the ways to promote the saving and discharge reduction of industrial wastewater for future potential metropolitan areas, thus providing a reference for macro water environment protection and governance in the Yangtze River Basin and other regional urban areas. HIGHLIGHTS The statistical data of industrial wastewater discharge (2005–2015) are analyzed.; The decomposition model of industrial wastewater discharge is constructed.; Decomposing the factors into technological improvement, industrial structure, economic growth, and the population size.; The temporal and spatial characteristics and driving factors are defined.; Guiding the protection and control of macro viewing water environment.;

Abstract Background To compare the accuracy of photogrammetry, intraoral scanning and conventional impression techniques for complete-arch implant rehabilitation. Methods A master cast containing 6 implant abutment replicas was fabricated. Group PG: digital impressions were taken 10 times using a photogrammetry system; Group IOS: intraoral scanning was performed to fabricate 10 digital impressions; Group CNV: splinted open-tray impression technique was used to fabricate 10 definitive casts. The master cast and conventional definitive casts were digitized with a laboratory reference scanner. For all STL files obtained, scan bodies were converted to implant abutment replicas using a digital library. The accuracy of a digitizer was defined by 2 main parameters, trueness and precision. "Trueness" was used to describe the deviation between test files and reference file, and "precision" was used to describe the closeness between test files. Then, the trueness and precision of three impression techniques were evaluated and statistically compared (α = 0.05). Results The median trueness was 24.45, 43.45 and 28.70 μm for group PG, IOS and CNV; Group PG gave more accurate trueness than group IOS (P

The contradiction between the ecological environment and economic development restricts the sustainable development of Wuhan Metropolitan Area (WMA). As an important carrier of the ecosystem in WMA, the change of ecological space can effectively reflect the ecological environment of WMA. Accordingly, based on various development needs and the Markov-FLUS model, this paper simulated the distribution of ecological space in WMA in 2035 under five scenarios, and discussed the characteristics of landscape structure and ecosystem service value of ecological space under five different scenarios. The results show that the Markov-FLUS model can properly simulate the future distribution of ecological space in WMA. Compared with 2020, the scale of ecological space under the natural development scenario (ND), the balanced and coordinated development scenario (BCD) and the ecological space preference development scenario (ESPD) increases, while the scale of the production space preference development scenario (PSPD) and the living space preference development scenario (LSPD) decreases. In the five scenarios, the areas of ecological spatial change are predominantly concentrated in the central urban area of Wuhan, the urban construction area of Ezhou, Huangshi and Huanggang, and the Dabie Mountain area in the northeast of Huanggang. Under the influence of human activities, the landscape structure of ecological space in WMA tended to be smaller in size, simplersize, simpler in boundary, more dispersed in distribution, and more uneven. Water and forest land play a major role in the ecosystem service value of ecological space in WMA, accounting for more than 95% of the value, and mostly play hydrological and climate regulation functions. The sustainable development and protection of ecological space under the BCD mode can provide reference for the policy implementation of sustainable development of territorial space and regional ecological security in WMA in the future.

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease with a complex and multifactorial etiology. An increased intrajoint pressure or weakened penetration can exacerbate the hypoxic state of the condylar cartilage microenvironment. Our group previously simulated the hypoxic environment of TMJOA in vitro. Low-intensity pulsed ultrasound (LIPUS) stimulation attenuates chondrocyte matrix degradation via a hypoxia-inducible factor (HIF) pathway-associated mechanism, but the mode of action of LIPUS is currently poorly understood. Moreover, most recent studies investigated the pathological mechanisms of osteoarthritis, but no biomarkers have been established for assessing the therapeutic effect of LIPUS on TMJOA with high specificity, which results in a lack of guidance regarding clinical application. Here, tandem mass tag (TMT)-based quantitative proteomic technology was used to comprehensively screen the molecular targets and pathways affected by the action of LIPUS on chondrocytes under hypoxic conditions. A bioinformatic analysis identified 902 and 131 differentially expressed proteins (DEPs) in the

Self-healing materials as a type of promising smart materials are gradually applied to electronics, biology, and engineering. In this study, we used in situ polymerization to make melamine-formaldehyde (MF) resin microcapsules to wrap the epoxy oxide as a repairing agent and Cu(MI)4Br2 as a latent-curing agent to protect epoxy oxide E-51 from broken melamine-formaldehyde resin microcapsules. In addition, graphene oxide was used as a reinforcing phase through its two-dimensional-layered structure to increase the tensile strength to 41.91 MPa, which is higher than the initial materials. The melamine-formaldehyde capsules and latent-curing agents were uniformly distributed in the materials according to the digital photos and scanning electron microscope (SEM) pictures. It is worth noting that the mechanical strength of the broken materials can be restored to 35.65 MPa after heating to 130°C for 2 h to repair the damage, and the self-healing efficiency reached up to 85.06%. Furthermore, we also fabricated the 4D printed material with a tensile strength of 50.93 MPa through a 3D printer. The obtained materials showed excellent repair effect, with a recovery rate of up to 87.22%. This study confirms that the designed self-healing system has potential applications in many areas due to its excellent self-healing performance, which provides valuable guidance for designing the 4D system.

β-glucan has attracted extensive attention due to its health promoting effects, such as lowering the blood sugar and lipids levels, and enhancing immunity. In this study, three different β-glucans (HEBG-1, HEBG-2, HEBG-3) were obtained from Hericium erinaceus by sodium hydroxide, β-1,3-glucanase and β-1,6-glucanase, respectively. The effects of the glucans on in vitro digestion of wheat starch were investigated by Englyst method. We found that addition of HEBGs significantly reduced the digestibility of starch, showing as decreased RDS and pGI, and increased SDS and RS content. In addition, the inhibitory effects positively correlated with the molecular weight of HEBG. The triple helix structure in HEBG plays important roles in inhibiting starch digestion. And β-1,3- glucan showed stronger inhibitor effects than those of β-1,6- glucan. This study unravels the mechanism of HEBG on inhibition of starch digestion and provides a theoretical understanding for the application of edible mushroom β-glucan to the development of low glycemic index starchy foods.

Cytology in China developed from nothing and underwent a long journey from gynecologic cytology to that of all organs, laying a solid foundation for new developments in the 21st century. Thyroid fine-needle aspiration (FNA) was primarily developed in an endocrinology department and then in the clinical laboratory department or pathology department in the 1970–80s. Wrights staining is popular in endocrine and clinical laboratory departments, while hematoxylin and eosin staining is common in pathology. Liquid based cytology is not common in thyroid FNA cytology, while BRAFV600E mutation analysis has been the most popular molecular test. The history and practice of thyroid FNA practice in China were reviewed based on retrospective study of the practice in Qilu Hospital of Shandong University.

Summary: HPV infections are common in healthy women and only rarely cause cervical cancer, suggesting that individual genetic susceptibility may play a critical role in the establishment of persistent HPV infection and the development of cervical cancer. Here, we provide convincing in vitro and in vivo evidence showing that differential expression and activation of YAP1 oncogene determine individual susceptibility to HPV infection and cervical carcinogenesis. We found that hyperactivation of YAP1 in mouse cervical epithelium was sufficient to induce invasive cervical cancer. Cervical epithelial cell-specific HPV16 E6/E7 and YAP1 double-knockin mouse model demonstrated that high-risk HPV synergized with hyperactivated YAP1 to promote the initiation and progression of cervical cancer. Our mechanistic studies indicated that hyperactivation of YAP1 in cervical epithelial cells facilitated HPV infection by increasing the putative HPV receptor molecules and disrupting host cell innate immunity. Our finding reveals an unconventional mechanism for cervical carcinogenesis. : HPV infections are common in healthy women and only rarely cause cervical cancer. He et al. provide evidence that hyperactivation of the YAP1 oncogene can drive cervical cancer initiation and progression. YAP1 hyperactivation in cervical epithelial cells increases the HPV receptors and disrupts host cell innate immunity, facilitating HPV infection. Keywords: Hippo pathway, YAP1 oncogene, HPV infection, cervical carcinogenesis, cervical cancer mouse model, innate immunity, molecular mechanism, HPV receptor molecules, type I interferon, interferon-stimulated genes

Prenatal stem cell-based regenerative therapies have progressed substantially and have been demonstrated as effective treatment options for fetal diseases that were previously deemed untreatable. Due to immunoregulatory properties, self-renewal capacity, and multilineage potential, autologous human placental chorionic villus-derived mesenchymal stromal cells (CV-MSCs) are an attractive cell source for fetal regenerative therapies. However, as a general issue for MSC transplantation, the poor survival and engraftment is a major challenge of the application of MSCs. Particularly for the fetal transplantation of CV-MSCs in the naturally hypoxic fetal environment, improving the survival and engraftment of CV-MSCs is critically important. Hypoxic preconditioning (HP) is an effective priming approach to protect stem cells from ischemic damage. In this study, we developed an optimal HP protocol to enhance the survival and proangiogenic capacity of CV-MSCs for improving clinical outcomes in fetal applications. Total cell number, DNA quantification, nuclear area test, and cell viability test showed HP significantly protected CV-MSCs from ischemic damage. Flow cytometry analysis confirmed HP did not alter the immunophenotype of CV-MSCs. Caspase-3, MTS, and Western blot analysis showed HP significantly reduced the apoptosis of CV-MSCs under ischemic stimulus via the activation of the AKT signaling pathway that was related to cell survival. ELISA results showed HP significantly enhanced the secretion of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) by CV-MSCs under an ischemic stimulus. We also found that the environmental nutrition level was critical for the release of brain-derived neurotrophic factor (BDNF). The angiogenesis assay results showed HP-primed CV-MSCs could significantly enhance endothelial cell (EC) proliferation, migration, and tube formation. Consequently, HP is a promising strategy to increase the tolerance of CV-MSCs to ischemia and improve their therapeutic efficacy in fetal clinical applications.