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Abstract DNA cleavage by nanomaterials has the potential to be utilized as an innovative tool for gene editing. Numerous nanomaterials exhibiting DNA cleavage properties have been identified and cataloged. Yet, the exploitation of property data through data-driven machine-learning approaches remains unexplored. A database was developed, compiling thirty distinctive characteristics, encompassing physical and chemical properties, as well as experimental conditions of nanomaterials that have demonstrated DNA cleavage capability such as in articles published over the past two decades. The DNA cleavage effect and efficiency of nanomaterials were predicted using machine learning algorithms such as support vector machines, deep neural networks, and random forest, and a classification accuracy of 0.93 for the cleavage effect was achieved. Moreover, the potential of utilizing larger datasets to enhance the predictive capacity of models was discussed. The findings indicate the feasibility of predicting nanomaterial properties based on experimental data. Evaluating the performance and effectiveness of the machine learning models trained using the existing data can furnish valuable insights for future materials research endeavors, especially for the design of DNA cleavage with specific sites.

Abstract Herein, thermally responsive reversible chiral supramolecules are reported, constructed by the chirality transfer from tripeptides to achiral network supramolecular organic frameworks (SOF) based on configurationally stepping confinement, which displayed not only highly selective reversible chirality transfer but also efficient enhanced near‐infrared (NIR) luminescence. Taking advantage of macrocyclic confinement, CB[8] separately encapsulated two kinds of tetracationic bis(phenothiazines) derivatives (G1, G2) at 2:1 stoichiometric to form organic 2D SOFs, efficiently enhancing 12.6 fold NIR luminescence and blueshifted from 705 to 680 nm for G1, and redshifted from 695 to 710 nm for G2, respectively. Uncommonly, the tripeptide coassembled with two kinds of achiral noncovalent frameworks (G1/CB[8] or G2/CB[8]) displayed different opposite circular dichroism signals based on different binding modes and affinity, achieving chirality transfer from tripeptide to organic supramolecular assemblies with further enhanced NIR fluorescence up to 46.2 times and the quantum yield (QY) increased from 0.71% to 10.29% for G2/CB[8], showing reversible chirality transfer and tunable NIR fluorescence under thermal stimulus. Therefore, the current research has achieved controllable chirality transfer from tripeptide to the SOFs and the enhancement of tunable NIR fluorescence, which is successfully applied in thermal responsive chiral logic gates, information encryption, and cell imaging.

Summary: Inflammatory bowel disease (IBD) has high prevalence in Western counties. The high fat content in Western diets is one of the leading causes for this prevalence; however, the underlying mechanisms have not been fully defined. Here, we find that high-fat diet (HFD) induces ferroptosis of intestinal regulatory T (Treg) cells, which might be the key initiating step for the disruption of immunotolerance and the development of colitis. Compared with effector T cells, Treg cells favor lipid metabolism and prefer polyunsaturated fatty acids (PUFAs) for the synthesis of membrane phospholipids. Therefore, consumption of HFD, which has high content of PUFAs such as arachidonic acid, cultivates vulnerable Tregs that are fragile to lipid peroxidation and ferroptosis. Treg-cell-specific deficiency of GPX4, the key enzyme in maintaining cellular redox homeostasis and preventing ferroptosis, dramatically aggravates the pathogenesis of HFD-induced IBD. Taken together, these studies expand our understanding of IBD etiology.

Celiac disease (CD), a gluten‐related disease, is a multi‐system rare disorder mainly involving the gastrointestinal tract. The clinical signs of CD are exceedingly heterogeneous, which increases the difficulty of clinical differential diagnosis. Neurological manifestations are one of the non‐classical CD symptoms. As some patients present only neurological symptoms at early stages, the diagnosis of CD is always delayed. Correct diagnosis and management could decrease patient morbidity and deaths. A 32‐year‐old male was admitted to the hospital due to progressive muscle atrophy of both lower limbs and lumbar stiffness. Based on positive gluten‐sensitive enteropathy autoantibody profiles and gastroscopy foundation, the diagnosis of CD was established. The patient was instructed to gluten‐free diet. The antibody titer of gluten‐sensitive enteropathy autoantibodies decreased, and the patient's symptoms alleviated. We emphasize the importance of CD screening in patients with neurological disorders of unknown aetiology.

The concept of “all cores are created equal” has been popular for several decades due to its simplicity and effectiveness in CPU (Central Processing Unit) design. The more cores the CPU has, the higher performance the host owns and the higher the power consumption. However, power-saving is also one of the key goals for servers in data centers and embedded devices (e.g., mobile phones). The big.LITTLE multicore architecture, which contains high-performance cores (namely big core) and power-saved cores (namely little core), has been developed by ARM (Advanced RISC Machine) and Intel to trade off performance and power efficiency. Facing the new heterogeneous computing architecture, the traditional lock algorithms, which are designed to run on homogeneous computing architecture, cannot work optimally as usual and drop into the performance issue for the difference between big core and little core. In our preliminary experiment, we observed that, in the big.LITTLE multicore architecture, all these lock algorithms exhibit sub-optimal performance. The FIFO-based (First In First Out) locks experience throughput degradation, while the performance of competition-based locks can be divided into two categories. One of them is big-core-friendly, so their tail latency increases significantly; the other is little-core-friendly. Not only does the tail latency increase, but the throughput is also degraded. Motivated by this observation, we propose a Core-Aware Lock for the big.LITTLE multicore architecture named CAL, which keeps each core having an equal opportunity to access the critical section in the program. The core idea of the CAL is to take the slowdown ratio as the matric to reorder lock requests of these big and little cores. By evaluating benchmarks and a real-world application named LevelDB, CAL is confirmed to achieve fairness goals in heterogeneous computing architecture without sacrificing the performance of the big core. Compared to several traditional lock algorithms, the CAL’s fairness has increased by up to 67%; and Its throughput is 26% higher than FIFO-based locks and 53% higher than competition-based locks, respectively. In addition, the tail latency of CAL is always kept at a low level.

Owing to environmental and lifestyle changes in modern society, physical and mental stress is on the rise among the population in attempting to compensate for the changes. Stress, defined as a series of non-specific responses to abnormal internal and external stimuli, has long been recognized to increase susceptibility to various diseases, including neurodegenerative diseases (NDs). Herpes simplex virus type 1 (HSV-1), a neurotropic herpes virus, establishes latent infections in the trigeminal ganglia for the lifetime of the host. Upon reactivation, the latent HSV-1 enters the lytic cycle, which not only causes a substantial production of reactive oxygen species (ROS) in the neurons, but also induces glial cells to produce inflammatory mediators, eventually resulting in neuronal damage and occurrence of NDs. Remarkably, both physical and psychological stress are common stimuli leading to latent HSV-1 reactivation. Acyclovir is a classic antiviral drug for the treatment of HSV-1 infection and recurrence, but acyclovir cannot reverse neuronal damage caused by HSV-1 reactivation. Recent studies have shown that traditional Chinese medicine (TCM) has advantages in the treatment of NDs. In addition, TCM is thought to prevent latent HSV-1 reactivation and NDs, which may involve regulation of the neuro-endocrine-immune network, treatment of emotional disorders, and modulation of oxidative stress. Understanding the mechanism underlying stress-induced reactivation of latent HSV-1 and the potential consequences of NDs is needed. TCM may be a promising alternative therapy for related diseases.

Although NAND (Not And) flash-based Solid-State Drive (SSD) has recently demonstrated a significant performance advantage against hard disk, it still suffers from non-negligible performance under-utilization issues as the access conflict often occurs during servicing IO requests due to the share mechanism (e.g., several chips share one channel bus, several planes share one data register inside the die). Many research works have been devoted to minimizing access conflict by redesigning IO scheduling, cache replacement, and so on. These works have achieved reasonable results; however, the potential data similarity characterization is not utilized fully in prior works to alleviate access conflict. The basic idea is that, as data duplication is common in many workloads where data with the same content from different requests could be distributed to the address with minimized access conflict (i.e., the address does not share the same channel or chip), the logic address is mapped to more than one physical address. Therefore, the data can be read out from candidate pages when the channel or chip of its original address is busy. Motivated by this idea, we propose Data Similarity aware Flash Translation Layer (DS-FTL), which mainly includes a content-aware page allocation scheme and a multi-path read scheme. The DS-FTL enables maximization of the channel-level and chip-level parallelism and avoids the read stall induced by bus-shared mechanisms. We also conducted a series of experiments on SSDsim, with the subsequent results depicting the effectiveness of our scheme. Compared with the state-of-art, our scheme reduces read latency by 35.3% on average in our workloads.

Firstly, the basic concept of network layer hopping technology was introduced and the security threats it faced were given.Then, two type of models and communication methods of network layer hopping technology based on traditional networks and software-defined networks were given.And the network layer hopping technology was classified from three aspects of hopping attributes, the method of hopping realization and the method of hopping trigger, two evaluation models of network layer hopping were given.Finally, the problems that still exist in the network layer hopping technology and the corresponding development direction were summarized.

Water resources are important for supporting regional economic development. A scientific and reasonable evaluation of the carrying capacity of water resources is of high significance to regional sustainable development. Zhangjiakou City is China’s first capital water conservation functional area, which plays a role in ensuring the safety of water resources and ecological environment in the capital. Considering Chicheng County, Zhangjiakou City, as a typical area, its water resource carrying capacity in the current year (2018) and the plan year (2025) is evaluated by constructing a water resource carrying capacity evaluation index system for the county, determining the threshold of the bearing capacity evaluation index, and using the single-factor evaluation method and cloud theory method. In addition, the main factors affecting the water resource carrying capacity of Chicheng County are analyzed. The results show that: Based on the single factor evaluation results, the critical state of water resources carrying capacity was evaluated comprehensively, and the factor carrying capacity of total water consumption in the predicted planning level year (38.0603 in normal water year and 41.3403 in dry water year) does not exceed the total water consumption index (51.14). Furthermore, The water resources carrying capacity level of the present level year (.45) and the planned level year (.46) belong to the third level of the evaluation index system. There is further scope for the carrying capacity of water resources in Chicheng County to satisfy its economic and social development. However, it is urgent to solve the problems affecting the water quality elements of rivers, such as heavy river water pollution, low sewage treatment capacity, and weak pollution monitoring and supervision. It is necessary to optimize the industrial economic structure of Chicheng County, accelerate the improvement of water resources management system and mechanism, and ensure the long-term safety of water resources and ecological environment in the capital.

To investigate the failure mode and strength characteristics of rock-like materials containing two non-coplanar closed discontinues, and the influence of crack attitude on the shear failure of rock mass, a series of direct shear tests are carried out on rock-like materials containing two pre-existing cracks of different attitudes, one of them is horizontal crack, and the other is inclined crack. The specimens containing pre-existing cracks of four inclinations (0°, 45°, 135°, and 180°) and three dip angles (30°, 60°, and 90°) are prepared, and the failure form and stress-displacement curve are recorded during the tests. The results show that the attitude of the crack has a significant effect on the failure form and strength characteristics. In positive shear, the shear stress increases slowly and the crack initiation of the crack occurs relatively late, and in negative shear, the shear stress increases rapidly and the crack initiation stage appears earlier. Under the normal stress of 1 MPa, the fracture surface fluctuates along the pre-existing cracks, and the difference in shear strength of each specimen is less than 1.0 MPa. Under the normal stress of 5 MPa, the fracture surface mostly distributes along the horizontal direction, and the difference in shear strength of each specimen is about 2.0 MPa. Under the same level of normal stress, the crack initiation and peak stress vary with the attitude of pre-existing crack, and the variation trend of peak stress is changed when the normal stress increased due to the difference in failure form. It is calculated that the ratio of crack initiation stress to peak stress ranges from 0.61 to 0.80.

Background: In this study, we analyzed intestinal flora in an experimental mouse model of chronic kidney disease (CKD) and investigated whether oral supplementation with probiotic Lactobacillus rhamnosus GG could slow the decline in renal function and inflammatory status of mice with CKD. Methods: We surgically induced chronic kidney disease in C57BL/6J male mice aged 8–9 weeks. We used dual-stage 5/6 nephrectomy for this, while the mock group underwent a mock procedure. The experimental (CKD mice) and mock group were administered a daily dose of 10 × 109 colony forming unit (CFU) of probiotic L. rhamnosus GG or 2 g of maltodextrin as a placebo by oral gavage, respectively, for 5 weeks. At the end of the experiment, the fecal samples of the mice were collected and prepared for intestinal microbial diversity analysis. We examined the serum chemistry and renal histology of the mice. Results: Important serum and blood biomarkers were associated with the development of CKD, including increased serum concentrations of creatine, cystatin C, blood urea nitrogen (BUN), and a protein—interleukin-6 (denoted as IL-6), whereas decreased serum albumin concentration was also observed in the mice with CKD. The intestinal flora of the mice with CKD significantly declined in terms of diversity, richness, and homogeneity. The consumption of L. rhamnosus GG probiotic via oral gavage significantly decreased the serum concentration level present in creatinine and blood urea nitrogen. However, it increased albumin in the group with CKD. After probiotic treatment, serum IL-6 levels dropped considerably, and the kidney histopathology score in mice with CKD who were given L. rhamnosus GG improved. Moreover, supplementation with the probiotic significantly improved floral richness and lineage diversity in the mice with CKD.Conclusions: In this study, we found that probiotics significantly attenuated renal failure development, reduced serum levels of proinflammatory cytokine IL-6, and increased the abundance and lineage diversity of intestinal flora in mice with chronic kidney disease.

Maternal stress has been associated with poor birth outcomes, including preterm birth, infant mortality, and low birth weight. Bone development disorders in the embryo as a result of maternal stress are believed to be mediated through oxidative stress damage. Various species of free radicals, such as alkoxyl radicals, can be formed through endogenous redox response or exogenous stimuli in the womb and transmitted to embryos. Yet, whether these free radicals lead to abnormal fetal bone development is unclear. Here, we demonstrate prenatal bone growth retardation and ferroptosis-related signals of chondrocytes were induced by classic alkoxyl radical generators. We also show that alkoxyl radicals lead to significant accumulation of oxidized phospholipids in chondrocytes, through the iron-mediated Fenton reaction in embryos. We further demonstrate a role for the lipid peroxidation end product, 4-HNE, which forms adducts with the pivotal chondrogenesis transcription factor SOX9, leading to its degradation, therefore dampening chondrogenesis. Our data define a critical role for phospholipid peroxidation in alkoxyl radicals-evoked abnormal chondrogenesis, and pinpoint it being a precise target for treating oxidative stress-related bone development disorders.

Traumatic brain injury (TBI) is a major cause of death and disability in the population worldwide, of which key injury mechanism involving the death of nerve cells. Many recent studies have shown that regulatory necrosis is involved in the pathological process of TBI which includes necroptosis, pyroptosis, ferroptosis, parthanatos, and Cyclophilin D (CypD) mediated necrosis. Therefore, targeting the signaling pathways involved in regulatory necrosis may be an effective strategy to reduce the secondary injury after TBI. Meanwhile, drugs or genes are used as interference factors in various types of regulatory necrosis, so as to explore the potential treatment methods for the secondary injury after TBI. This review summarizes the current progress on regulatory necrosis in TBI.

Abstract The occurrence of toxic metals in the aquatic environment is as caused by a variety of contaminations which makes difficulty in the concentration prediction. In this study, conventional methods of back-propagation neural network (BPNN) and nonlinear autoregressive network with exogenous inputs (NARX) were applied as benchmark models. Explanatory variables of Fe, pH, electrical conductivity, water temperature, river flow, nitrate nitrogen, and dissolved oxygen were used as different input combinations to forecast the long-term concentrations of As, Pb, and Zn. The wavelet transformation was applied to decompose the time series data, and then was integrated with conventional methods (as WNN and WNARX). The modelling performances of the hybrid models of WNN and WNARX were compared with the conventional models. All the given models were trained, validated, and tested by an 18-year data set and demonstrated based on the simulation results of a 2-year data set. Results revealed that the given models showed general good performances for the long-term prediction of the toxic metals of As, Pb, and Zn. The wavelet transform could enhance the long-term concentration predictions. However, it is not necessarily useful for each metal prediction. Therefore, different models with different inputs should be used for different metals predictions to achieve the best predictions.

Tetrandrine citrate (TetC), a novel tetrandrine salt with high water solubility, demonstrates a potent antitumor activity in chronic myeloid leukemia. Studies have indicated an important role of ferroptosis in breast cancer (BC). However, whether TetC inhibits BC progression via ferroptosis has never been explored. In the present study, we showed that TetC had a significant inhibitory effect on the proliferation and migration of MCF7 and MDA-MB-231 cells. Then, we combined TetC with different inhibitors to determine which form of cell death could be driven by TetC. MTT assay showed that ferrostatin (Fer-1) demonstrated the most potent effect on improving TetC-induced cell death in contrast to other inhibitors. TetC was also shown to significantly increase the mRNA level of prostaglandin-endoperoxide synthase 2 (Ptgs2), a ferroptosis marker. Further studies showed that TetC significantly suppressed the expression of glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1) but increased the expression of nuclear receptor coactivator 4 (NCOA4) in MCF7 and MDA-MB-231 cells even in the presence of erastin or Ras-selective lethal 3 (RSL3). Collectively, we showed novel data that ferroptosis was a major form of TetC-induced cell death. Moreover, TetC-induced ferroptotic cell death was achieved via suppressing GPX4 expression and activating NCOA4-mediated ferritinophagy in BC cells.

Based on the analysis of air quality data in Yunnan Province from 2015 to 2020, combined with spatial interpolation analysis and geographic detector factor analysis, the spatial–temporal evolution characteristics of air quality in Yunnan Province have been studied, and the main driving factors, the mechanisms, and the impact of regional COVID-19 control measures affecting air quality have been discussed. The results show that the air quality in Yunnan Province was generally good (superior rate > 98%) from 2015 to 2020, that the Air Quality Index (AQI) value is better in the wet season than in the dry season, and that the concentration of major pollutants shows a decreasing trend. AQI values are spatially high in the east and low in the west. The relative humidity, precipitation, population density, building construction area, and civil vehicles have a greater degree of explanation for the spatial differentiation of AQI, whereas the synergistic influence (maximum value 0.92) of socio-economic factors and meteorological factors is significantly greater than that of a single factor (maximum value 0.80) by the geographic detector model. The control measures for COVID-19 in 2020 reduced the concentration of major pollutants in the atmosphere to a certain extent. Controlling regional air pollution in urban agglomerations in low-latitude plateau areas can improve their air quality by reducing human activities. However, the control of O3 concentration is more complex, and more restrictive factors need to be considered. The results will provide a scientific basis for the prevention and control of air pollution in plateau cities.

Abstract Background Crocetin is a major active component of saffron, which has a wide range of pharmacological effects. However, due to its low solubility, the pharmacological effects of crocetin cannot be better utilized. Methods In this study, we modified the chemical structure of crocetin by conjugating with ethylamine and 4-Fluorbenzylamine to enhance its solubility and biological activities. The solubility and the influence of synthesized derivatives on the proliferation of tumor cells and the inflammatory effect of macrophage were investigated. Results It was shown that, compared with the crocetin, the synthesized derivatives have much higher solubility. Moreover, the inhibitory effect of the derivatives on varieties of tumor cells, including human ovarian carcinoma cell line, human lung cancer cell line, rat melanoma cell line was enhanced after the modification. Besides that, the derivatives were improved for the anti-inflammatory efficacy with the cytotoxicity decreased. Conclusions The synthesized derivatives were shown for their good solubility and the great potential in tumor and inflammation treatment.

The depression-like behavior phenotype, neurogenesis in the dentate gyrus and miR-124 expression in the hippocampus are the focus of current research on the pathogenesis of depression and antidepressant therapy. The present study aimed to clarify the dynamic changes of depression-like behavior, dentate gyrus neurogenesis and hippocampal miR-124 expression during depression induced by chronic stress to reveal pathological features at different stages of depression and to further provide insight into depression treatment. Chronic unpredictable mild stress depression models were established by exposing Sprague-Dawley rats to various mild stressors, including white noise, thermal swimming, stroboscopic illumination, soiled cages, pairing with three other stressed animals, cold swimming, tail pinch, restraint and water and food deprivation. Chronic unpredictable mild stress model rats underwent dynamic observation from 1 to 8 weeks and were compared with a control group (normal feeding without any stressors). To observe changes in the depression-like behavior phenotype during chronic unpredictable mild stress-induced depression, a sucrose preference test was used to evaluate the degree of anhedonia. An open-field test was used to evaluate locomotor activity and anxiety status. Compared with the control group, chronic unpredictable mild stress rats lost weight but did not have a depression-like behavioral phenotype at 1–4 weeks. Chronic unpredictable mild stress rats presented decreased sucrose preference and locomotor activity at 5–8 weeks. In addition, chronic unpredictable mild stress rats did not have significant anxiety-like behavior during 1–8 weeks of modeling. To observe neurogenesis dysfunctions and changes in neuronal number in the dentate gyrus during chronic unpredictable mild stress-induced depression, markers (DCX and DCX/BrdU) of neural proliferation and differentiation and the neuronal marker NeuN were assessed by immunofluorescence. Compared with the control group, neurogenesis and the neuronal number in the dentate gyrus did not change from 2 to 6 weeks; however, neural proliferation and differentiation in the dentate gyrus decreased, and the number of neurons decreased until the eighth week in the chronic unpredictable mild stress group. Real-time quantitative reverse transcription polymerase chain reaction assays and fluorescence in situ hybridization were used to measure the expression of hippocampal miR-124 during chronic unpredictable mild stress-induced depression. The results showed that the expression of hippocampal miR-124 was unchanged during the first 4 weeks but increased from 5 to 6 weeks and decreased from 7 to 8 weeks compared with the control group. These findings indicate that during chronic unpredictable mild stress-induced depression, the behavioral phenotype, miR-124 expression in the hippocampus, neurogenesis in the dentate gyrus and neuronal numbers showed dynamic changes, which suggested that various pathological changes occur at different stages of depression. All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2015.

Abstract Background DKK1 has been reported to act as a tumor suppressor in breast cancer. However, the mechanism of DKK1 inhibits breast cancer migration and invasion was still unclear. Methods Western blot and real time PCR was used to detect the expression of DKK1, β-catenin and MMP7 in breast cancer cells. Wound scratch assay and transwell assay was employed to examine migration and invasion of breast cancer cell. Results DKK1 overexpression dramatically inhibits breast cancer cell migration and invasion. Knockdown of DKK1 promotes migration and invasion of breast cancer cells. DKK1 suppressed breast cancer cell migration and invasion through suppression of β-catenin and MMP7 expression. XAV-939, an inhibitor of β-catenin accumulation could reverse DKK1 silencing-induced MMP7 expression in breast cancer cells. Meanwhile, XAV-939 also could reverse the increase in the cell number invaded through Matrigel when DKK1 was knockdown. Furthermore, depletion of MMP7 also could reverse DKK1 knockdown-induced increase in the cell number invaded through Matrigel. Conclusions DKK1 inhibits migration and invasion of breast cancer cell through suppression of β-catenin/MMP7 pathway, our findings offered a potential alternative for breast cancer prevention and treatment.

To improve the robotic assembly effects in unstructured environments, a reinforcement learning (RL) algorithm is introduced to realize a variable admittance control. In this article, the mechanisms of a peg-in-hole assembly task and admittance model are first analyzed to guide the control strategy and experimental parameters design. Then, the admittance parameter identification process is defined as the Markov decision process (MDP) problem and solved with the RL algorithm. Furthermore, a fuzzy reward system is established to evaluate the action–state value to solve the complex reward establishment problem, where the fuzzy reward includes a process reward and a failure punishment. Finally, four sets of experiments are carried out, including assembly experiments based on the position control, fuzzy control, and RL algorithm. The necessity of compliance control is demonstrated in the first experiment. The advantages of the proposed algorithms are validated by comparing them with different experimental results. Moreover, the generalization ability of the RL algorithm is tested in the last two experiments. The results indicate that the proposed RL algorithm effectively improves the robotic compliance assembly ability.

Objective: This study aimed to construct a prognostic ferroptosis-related signature for thyroid cancer and probe into the association with tumor immune microenvironment.Methods: Based on the expression profiles of ferroptosis-related genes, a LASSO cox regression model was established for thyroid cancer. Kaplan-Meier survival analysis was presented between high and low risk groups. The predictive performance was assessed by ROC. The predictive independency was validated via multivariate cox regression analysis and stratified analysis. A nomogram was established and verified by calibration curves. The enriched signaling pathways were predicted via GSEA. The association between the signature and immune cell infiltration was analyzed by CIBERSORT. The ferroptosis-related genes were validated in thyroid cancer tissues by immunohistochemistry and RT-qPCR.Results: A ferroptosis-related eight gene model was established for predicting the prognosis of thyroid cancer. Patients with high risk score indicated a poorer prognosis than those with low risk score (p = 1.186e-03). The AUCs for 1-, 2-, and 3-year survival were 0.887, 0.890, and 0.840, respectively. Following adjusting other prognostic factors, the model could independently predict the prognosis (p = 0.015, HR: 1.870, 95%CI: 1.132–3.090). A nomogram combining the signature and age was constructed. The nomogram-predicted probability of 1-, 3-, and 5-year survival approached the actual survival time. Several ferroptosis-related pathways were enriched in the high-risk group. The signature was distinctly associated with the immune cell infiltration. After validation, the eight genes were abnormally expressed between thyroid cancer and control tissues.Conclusion: Our findings established a prognostic ferroptosis-related signature that was associated with the immune microenvironment for thyroid cancer.

Organic room‐temperature phosphorescence (RTP) has attracted tremendous attention in recent years due to its potential utility in combination with artificial soft materials. Herein, a room‐temperature‐phosphorescent hybrid xerogel held together by electrostatic and host–guest interactions is reported. The xerogel is constructed by noncovalent complexation of 7‐[6‐deoxy‐6‐(2‐sulfonic)]‐β‐cyclodextrin (SCD) with the phosphor bromophenyl‐methyl‐pyridinium chloride (PYCl) and in situ incorporation of the anionic SCD⊃PYCl complex into a cationic amino clay (AC) via electrostatic interactions. The resulting xerogel, designated AC/SCD⊃PYCl, has a network structure that can suppress vibrational and nonradiative relaxation of the phosphor, leading to green RTP emission as well as good fluorescence–phosphorescence dual emission. Notably, the intensity of the xerogel RTP varies with humidity and can be switched on and off repeatedly, which indicates that the xerogel has potential utility as an organic light‐emitting humidity‐sensing material.

In this work, we propose a robust place recognition measurement in natural environments based on salient landmark screening and convolutional neural network (CNN) features. First, the salient objects in the image are segmented as candidate landmarks. Then, a category screening network is designed to remove specific object types that are not suitable for environmental modeling. Finally, a three-layer CNN is used to get highly representative features of the salient landmarks. In the similarity measurement, a Siamese network is chosen to calculate the similarity between images. Experiments were conducted on three challenging benchmark place recognition datasets and superior performance was achieved compared to other state-of-the-art methods, including FABMAP, SeqSLAM, SeqCNNSLAM, and PlaceCNN. Our method obtains the best results on the precision–recall curves, and the average precision reaches 78.43%, which is the best of the comparison methods. This demonstrates that the CNN features on the screened salient landmarks can be against a strong viewpoint and condition variations.

The Tarim River Basin (TRB) is one of the world’s largest cotton-producing areas, and its agricultural water use accounts for up to 95% of the total water consumption in the basin. Quantifying the future changes in the irrigation area carrying capacity under global warming is therefore essential in TRB. In this study, we analyzed the variation in the irrigation area in TRB over the last few decades, utilized the nonlinear autoregressive with an exogenous input neural network to simulate the future changes in the available water resources, and predicted the future irrigation area carrying capacity based on the water balance equation. The results showed that the present (1970–2020) irrigation area in TRB exhibited an increasing trend from 491 km2 in 1970s to 1382 km2 in 2020, as most of the natural vegetation was transformed into cropland. In the future (2022–2050), the available water resource will show an upward tendency while the irrigation area carrying capacity mainly ranges from 12×102–21×102 km2 and 17×102–30×102 km2 under scenarios SSP (shared socioeconomic pathway) 245 and SSP585, respectively. The simulated results will provide useful information for the allocation of water resources and the regional sustainable development of TRB.

Abstract Background Knockdown of Akt1 promotes Epithelial-to-Mesenchymal Transition in breast cancer cells. However, the mechanisms are not completely understood. Methods Western blotting, immunofluorescence, luciferase assay, real time PCR, ELISA and Matrigel invasion assay were used to investigate how Akt1 inhibition promotes breast cancer cell invasion in vitro. Mouse model of lung metastasis was used to measure in vivo efficacy of Akt inhibitor MK2206 and its combination with Gefitinib. Results Knockdown of Akt1 stimulated β-catenin nuclear accumulation, resulting in breast cancer cell invasion. β-catenin nuclear accumulation induced by Akt1 inhibition depended on the prolonged activation of EGFR signaling pathway in breast cancer cells. Mechanistic experiments documented that knockdown of Akt1 inactivates PIKfyve via dephosphorylating of PIKfyve at Ser318 site, resulting in a decreased degradation of EGFR signaling pathway. Inhibition of Akt1 using MK2206 could induce an increase in the expression of EGFR and β-catenin in breast cancer cells. In addition, MK2206 at a low dosage enhance breast cancer metastasis in a mouse model of lung metastasis, while an inhibitor of EGFR tyrosine kinase Gefitinib could potentially suppress breast cancer metastasis induced by Akt1 inhibition. Conclusion EGFR-mediated β-catenin nuclear accumulation is critical for Akt1 inhibition-induced breast cancer metastasis.

AIM:To explore the effects of femtosecond laser-assisted cataract surgery(FLACS)on corneal astigmatism and surgically induced astigmatism(SIA)value in patients with age-related cataract. METHODS: Totally 152 cases of age-related cataract patients(233 eyes)admitted to our hospital were divided into the study group(n=70, 107 eyes, given the FLACS)and the control group \〖n=82, 126 eyes, given the traditional phacoemulsification cataract surgery(TS)\〗 according to the economic conditions and voluntary principles. Corneal astigmatism degree and SIA value were compared between the two groups. RESULTS: The effective ultrasound time, average ultrasound energy, and total operative time in the study group were less than those in the control group(PP>0.05). The difference in intraocular pressure was statistically significant of the two groups at different time points(PPPPPPP>0.05). There was no significant difference in corneal astigmatism between the two groups and at different time points(P>0.05). There was no significant difference in surgical astigmatism between-groups at 1 and 3mo after operation(P>0.05).The surgical astigmatism at 3mo after operation was lower than that at 1mo after operation(PPP>0.05). The corneal endothelial cell counts in control group at 1mo after operation was lower than that before operation(PP>0.05). The corneal endothelial cell counts in the study group were significantly more than those in the control group at 3mo after operation(PPCONCLUSION: FLACS can effectively improve the postoperative visual acuity in patients with age-related cataract, and it will not increase the postoperative corneal astigmatism and SIA.

Abstract Background Kangfuxin (KFX) is the ethanol extract of Periplaneta americana L, which has been widely used in the Traditional Chinese Medicine for the repair and regeneration of injured organ and tissues with long history. This study is to investigate the influence of KFX in the various cellular activities and evaluate the anti-osteoporosis potential of KFX. Methods The influence of the KFX in the cellular activities, including: 1) migration, osteocalcin secretion of osteoblasts; 2) apoptosis of osteoclasts; 3) migration and tube formation of human umbilical vein endothelial cell (HUVEC); and 4) proliferation, cell cycle regulation and migration of bone marrow mesenchymal stem cells (BMSCs), were investigated systematically. Results KFX was shown to significantly 1) Promote of the migration of osteoblasts, HUVEC, and BMSCs; 2) Increase the secretion of osteocalcin and mineralization of osteoblasts; 3) Accelerate the apoptosis of osteoclasts; 4) Stimulate the proliferation and regulate the cell cycle of BMSCs. Conclusion Taken together, these results provide the evidence for the osteogenesis, anti-osteoporosis and angiogenesis effects of KFX, with the mechanism of activating the bone formation through stimulating the osteoblasts and HUVECs, as well as inhibiting the bone absorption by inhibiting the osteoclasts activities. The KFX was definitely shown a promising bone turnover agent with great potential for anti-osteoporosis treatment.

Abstract Hydrogen peroxide (H2O2) plays a key role in the progression of human illnesses, such as autoimmune and auto-inflammatory diseases, infectious diseases, diabetes, and cancer, etc. In this work, we have discribed a novel probe, TPE-TLE, which remarkably displayed AIE property and ratiometric fluorescence emission profiles in the presence of H2O2. This ratiometric fluorescent probe with AIE property exhibits outstanding features such as the well-resolved emission peaks, high sensitivity, high selectivity, low cytotoxicity, and good cell-membrane permeability. These excellent attributes enable us to demonstrate the ratiometric imaging of endogenously produced H2O2 in macrophages and cancer cells based on the novel ratiometric probe with AIE property for the first time. By comparing two kinds of cells, it is firstly found that cancer cells should contain much more endogenous H2O2 than macrophages. We expect that TPE-TLE will be useful fluorescent platform for the development of a variety of ratiometric fluorescent probes with AIE property to achieve unique biological applications.

AIM: To investigate the relationship of TNF-α and IL-6 with the pathogenesis and development of the neovascular glaucoma(NVG). METHODS: Totally 64 eyes of 64 NVG patients, 58 eyes of 58 primary open angle glaucoma(POAG)patients and 56 eyes of 56 age-related cataract(ARC)patients were enrolled in our Hospital from January 2017 to January 2018. The periphery blood was collected from all the patients and 0.3mL aqueous humor was collected during the surgery from each eye. The levels of TNF-α and IL-6 in serum and aqueous humor of the three groups were measured by ELISA.RESULTS: The concentrations of TNF-α and IL-6 in aqueous humor and serum in NVG patients were higher than those in POAG patients as well as in ARC patients, with significant differences among the three groups(Pr=0.642, 0.415; PCONCLUSION: The aqueous and serum TNF-α and IL-6 are considerably higher in NVG patients than those in POAG patients and ARC patients, suggesting that TNF-α and IL-6 play important roles in the pathogenesis and development of the NVG.

Correct cognition of the environment is the premise of mobile robots to realize autonomous navigation control tasks. The inconsistency caused by time-varying environmental information is a bottleneck for the development and application of cognitive environment technologies. In this article, we propose an environmental cognition method that uses a hand-drawn map. Firstly, we use the single skeleton refinement and fuzzy c-means algorithms to segment the image. Then, we select candidate regions combining the saliency map. At the same time, we use the superpixels straddling method to filter the windows. The final candidate object regions are obtained based on a fusion of saliency segmentation and superpixels clustering. Based on the above objectness estimation results, we use a human–computer interaction method to construct an inaccurate hand-drawn environment map for navigation. The experimental results from PASCAL VOC2007 validate the efficacy of the proposed objectness measure method, where our result of 41.2% on mean average precision is the best of the tested methods. Furthermore, the experimental results of robot navigation in the actual scene also verified the effectiveness of the proposed approach.

In the synthetic aperture radar (SAR) imaging of ship-induced wakes, it is difficult to obtain the Doppler velocity of a Kelvin wake due to the lack of time-varying wake models and suitable radar equipment. The conventional Kelvin wake investigation based on the static Kelvin wake model failed to reflect time-varying characteristics, which are significant in the application of the Kelvin wake model. Therefore, a time-varying Kelvin wake model with consideration of geometric time-varying characteristics and the hydrodynamic equation is proposed in this paper, which reflects the wake’s time-varying change lacking in the conventional Kelvin wake investigation. The Doppler velocity measurement, measured by a specially designed radar, can be exploited to verify the time-varying model by the comparison of velocity fields. Ground-based multi-input multi-output (MIMO) millimeter wave radar imaging through the simultaneous switching of transceiver channels was used to obtain the Doppler velocity for the first time. Finally, promising results have been achieved, which are in good agreement with our proposed model in consideration of the experimental scene. The proposed time-varying model and radar equipment provide velocity measurements for the Kelvin wake observation, which contains huge application potential.

Physiological characteristics of human malignancies are increased glycolysis and overexpression of glucose transporters (GLUTs). 18Flurodeoxyglucose-positron emission tomography (FDG-PET) has successfully developed as clinical modality for the diagnosis and staging of many cancers based on the Warburg effect. To leverage this glucose transporter mediated metabolic disparity between normal and malignant cells, in the current report, protected, and de-protected glucose, mannose, galactose, rhamnose, maltose, and lactose-conjugated platinum(IV) complexes were designed and synthesized. The suggested potential of facilitated intravenous to oral switching of glycosylated platinum(IV) prodrugs with cancer-targeting properties were evaluated for glucose transporter 1 (GLUT1) and organic cation transporter 2 (OCT2)-mediated selective properties in vitro and in vivo. The cytotoxicity of 2d, 5d, and 6d were ~23-fold greater than that of the positive controls cisplatin, oxaliplatin, and satraplatin, respectively. The leading compound 6d, the IC50 of which with the GLUT1 inhibitor 4,6-oethylidene-α-D-glucose (EDG) and phloretin (31.80 and 38.71 μM) are 36- and 44-folds higher, respectively, than the 48 h IC50 (0.89 μM), is superior to the reported 5-8, exhibiting enhanced cancer targeting. The compounds also showed reduced toxicity to normal cells (293T IC50 = 12.06 μM and 3T3 cells IC50 > 100 μM) and exhibited no cross-resistance to cisplatin. Moreover, the encouraging selectivity of 6d for MCF-7 cells in vivo indicated that the pyranoside performs an important function in cancer targeting.

Because of uncertainties involved in modeling, construction, and measurement systems, the assessment of the FE model validation must be conducted based on stochastic measurements to provide designers with confidence for further applications. In this study, based on the updated model using response surface methodology, a practical model validation methodology via uncertainty propagation is presented. Several criteria of testing/analysis correlation are introduced, and the sources of model and testing uncertainties are also discussed. After that, Monte Carlo stochastic finite element (FE) method is employed to perform the uncertainty quantification and propagation. The proposed methodology is illustrated with the examination of the validity of a large-span prestressed concrete continuous rigid frame bridge monitored under operational conditions. It can be concluded that the calculated frequencies and vibration modes of the updated FE model of Xiabaishi Bridge are consistent with the measured ones. The relative errors of each frequency are all less than 3.7%. Meanwhile, the overlap ratio indexes of each frequency are all more than 75%; The MAC values of each calculated vibration frequency are all more than 90%. The model of Xiabaishi Bridge is valid in the whole operation space including experimental design space, and its confidence level is upper than 95%. The validated FE model of Xiabaishi Bridge can reflect the current condition of Xiabaishi Bridge, and also can be used as basis of bridge health monitoring, damage identification and safety assessment.

In the engineering practice, merging statistical analysis into structural evaluation and assessment is a tendency in the future. As a combination of mathematical and statistical techniques, response surface (RS) methodology has been successfully applied to design optimization, response prediction and model validation. With the aid of RS methodology, these two serial papers present a finite element (FE) model updating and validation method for bridge structures based on structural health monitoring. The key issues to implement such a model updating are discussed in this paper, such as design of experiment, parameter screening, construction of high-order polynomial response surface model, optimization methods and precision inspection of RS model. The proposed procedure is illustrated by a prestressed concrete continuous rigid-frame bridge monitored under operational conditions. The results from the updated FE model have been compared with those obtained from online health monitoring system. The real application to a full-size bridge has demonstrated that the FE model updating process is efficient and convenient. The updated FE model can relatively reflect the actual condition of Xiabaishi Bridge in the design space of parameters and can be further applied to FE model validation and damage identification.

Robot-aided rehabilitation has become an important technology to restore and reinforce motor functions of patients with extremity impairment, whereas it can be extremely challenging to achieve satisfactory tracking performance due to uncertainties and disturbances during rehabilitation training. In this paper, a wire-driven rehabilitation robot that can work over a three-dimensional space is designed for upper-limb rehabilitation, and sliding mode control with nonlinear disturbance observer is designed for the robot to deal with the problem of unpredictable disturbances during robot-assisted training. Then, simulation and experiments of trajectory tracking are carried out to evaluate the performance of the system, the position errors, and the output forces of the designed control scheme are compared with those of the traditional sliding mode control (SMC) scheme. The results show that the designed control scheme can effectively reduce the tracking errors and chattering of the output forces as compared with the traditional SMC scheme, which indicates that the nonlinear disturbance observer can reduce the effect of unpredictable disturbances. The designed control scheme for the wire-driven rehabilitation robot has potential to assist patients with stroke in performing repetitive rehabilitation training.

Background: Bone marrow-derived mesenchymal stem cells (bmMSCs) are the most promising seed cells for cell transplant therapy. Hypoxia is a known stimulus of autophagy. Recent studies showed that hypoxia promotes autophagy of human placental chorionic plate-derived mesenchymal stem cells (CP-MSCs). However, whether hypoxia affects autophagy of bmMSCs has not been examined. The goal of this study was to investigate the effect of hypoxia on autophagy of mouse bmMSCs and the underlying mechanisms. Methods: BmMSCs from mouse bone marrow were randomly divided into three groups: control (C), hypoxia (H) and hypoxia + reoxygenation (H+R) groups. Subsequent autophagic signals were analyzed by immunostaining and Western blot assays. Results: The expression of autophagic signals LC-3, Atg5 and Beclin-1, as well as the conversion of LC3B-I to LC3B-II in bmMSCs were significantly increased in H group as compared with control (pConclusion: Hypoxia can induce autophagy of bmMSCs, which depends on activation of ERK1/2 pathway.

Lacustrine deposits at the margin of the southeastern Tibetan Plateau (SETP) are sensitive indicators for the evolution of the southwest Asian monsoon (SWAM) during the Quaternary. Thus, they can provide insight into the Quaternary climatic history and their relationship with global climatic changes. The results of the geochemical analysis of the Xiaozhongdian Basin section at the SETP suggest that SiO2 had the highest content of the major elements followed by Al2O3. The order of the abundance of the major elements was generally as follows: SiO2>Al2O3>Fe2O3>CaO>MgO>K2O>TiO2>Na2O>MnO2. The geochemical proxies, such as chemical index of alteration (CIA), the index of compositional variability (ICV) and (CaO+K2O+Na2O)/Al2O3, indicate the weak chemical weathering and the aridification of the margin of the SETP during the Heinrich events. In addition, the aridification of the SETP during the Heinrich events may be closely related to the cold signals transmitted from the high latitudes of the North Atlantic to the TP, and the effect caused the cooling effect to be very strong on the TP as a result of the upper-level westerly jet stream and then reduced the suction action associated with the SWAM, thus accelerating the drying rate of Xiaozhongdian Basin, which was amplifying the degree of drought in Heinrich events.

Sediments from Xinyun Lake in central Yunnan, southwest China, provide a record of environmental history since the Holocene. With the application of multi-proxy indicators (total organic carbon (TOC), total nitrogen (TN), δ13C and δ15N isotopes, C/N ratio, grain size, magnetic susceptibility (MS) and CaCO3 content), as well as accelerator mass spectrometry (AMS) 14C datings, four major climatic stages during the Holocene have been identified in Xingyun's catchment. A marked increase in lacustrine palaeoproductivity occurred from 11.06 to 9.98 cal. ka BP, which likely resulted from an enhanced Asian southwest monsoon and warm-humid climate. Between 9.98 and 5.93 cal. ka BP, a gradually increased lake level might have reached the optimum water depth, causing a marked decline in coverage by aquatic plants and lake productivity of the lake. This was caused by strong Asian southwest monsoon, and coincided with the global Holocene Optimum. During the period of 5.60-1.35 cal. ka BP, it resulted in a warm and dry climate at this stage, which is comparable to the aridification of India during the mid- and late Holocene. The intensifying human activity and land-use in the lake catchment since the early Tang Dynasty (∼1.35 cal. ka BP) were associated with the ancient Dian culture within Xingyun's catchment. The extensive deforestation and development of agriculture in the lake catchment caused heavy soil loss. Our study clearly shows that long-term human activities and land-use change have strongly impacted the evolution of the lake environment and therefore modulated the sediment records of the regional climate in central Yunnan for more than one thousand years.

The Caenorhabditis elegans DAF-16 transcription factor is critical for diverse biological processes, particularly longevity and stress resistance. Disruption of the DAF-2 signaling cascade promotes DAF-16 activation, and confers resistance to killing by pathogenic bacteria, such as Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. However, daf-16 mutants exhibit similar sensitivity to these bacteria as wild-type animals, suggesting that DAF-16 is not normally activated by these bacterial pathogens. In this report, we demonstrate that DAF-16 can be directly activated by fungal infection and wounding in wild-type animals, which is independent of the DAF-2 pathway. Fungal infection and wounding initiate the Gαq signaling cascade, leading to Ca(2+) release. Ca(2+) mediates the activation of BLI-3, a dual-oxidase, resulting in the production of reactive oxygen species (ROS). ROS then activate DAF-16 through a Ste20-like kinase-1/CST-1. Our results indicate that DAF-16 in the epidermis is required for survival after fungal infection and wounding. Thus, the EGL-30-Ca(2+)-BLI-3-CST-1-DAF-16 signaling represents a previously unknown pathway to regulate epidermal damage response.