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Abstract The fast and safe formation tracking problem for multiple autonomous underwater vehicle (AUV) systems (MAUVS) with asymmetric output constraints and actuator faults is studied in this article. Actuator faults are composed of loss of effectiveness and time‐varying unknown bias faults, an adaptive fixed‐time fault‐tolerant controller (AFFTC) is designed by employing fixed‐time stable theory and fuzzy logic systems. Under the designed control algorithm, the MAUVS can be practically fixed‐time stable, the tracking errors among the follower AUVs and the virtual leader AUV can converge to a small area near the origin within the fixed time, and the settling time is unaffected by the initial state of the system. To enhance the safety of MAUVS, a novel asymmetric barrier function is utilized to constrain the trajectory tracking errors within the prescribed range. Finally, the simulation results demonstrate the effectiveness of the proposed control algorithm.

Abstract Abnormal subchondral bone remodeling plays a pivotal role in the progression of osteoarthritis (OA). Here, we analyzed subchondral bone samples from OA patients and observed a significant upregulation of ubiquitin carboxy-terminal hydrolase L1 (UCHL1) specifically in subchondral bone osteoclasts. Notably, we found a strong correlation between UCHL1 expression and osteoclast activity in the subchondral bone during OA progression in both human and murine models. Conditional UCHL1 deletion in osteoclast precursors exacerbated OA progression, while its overexpression, mediated by adeno-associated virus 9, alleviated this process in male mice. Mechanistically, RANKL stimulates UCHL1 expression in osteoclast precursors, subsequently stabilizing CD13, augmenting soluble CD13 (sCD13) release, and triggering an autocrine inhibitory effect on the MAPK pathway, thereby suppressing osteoclast formation. These findings unveil a previously unidentified negative feedback loop, RANKL-UCHL1-sCD13, that modulates osteoclast formation and presents a potential therapeutic target for OA.

Transcriptional factor Forkhead box M1 (FOXM1) plays an important role in pancreatic ductal adenocarcinoma (PDAC) development and progression. The molecular mechanisms underlying its dysregulation remain unclear. We identified and functionally validated the microRNAs (miRNAs) that critically regulate FOXM1 expression in PDAC. The expression levels of miRNA-23a (miR-23a-3p and -5p) were altered in PDAC cell lines and their effects on FOXM1 signaling and cell proliferation and migration and tumorigenesis were examined in vitro and in vivo using mouse PDAC models. Compared with non-tumor pancreatic tissues, PDAC tissues and cell lines exhibited significantly reduced levels of miR-23a expression. Reduced miR-23a expression and concomitant increase in FOXM1 expression were also observed in acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasia, the major premalignant lesions of PDAC. Transgenic expression of miR-23a reduced the expression of FOXM1 and suppressed cell proliferation and migration in PDAC cells, whereas the inhibitors of miR-23a did the opposite. Loss or reduced levels of miR-23a increased the levels of FOXM1 expression, while increased expression of FOXM1 down-regulated miR-23a expression, suggesting that miR-23a and FOXM1 were mutual negative regulators of their expression in PDAC cells. Therefore, the miR-23a/FOXM1 signaling axis is important in PDAC initiation and progression and could serve as an interventional or therapeutic target for patients with early or late stages of PDAC.

Abstract In this paper, we analysed the temporal and spatial distributions of ancient archaeological sites in China as well as their influencing factors. Our aim was to reveal the developmental trajectory of Chinese civilisation and to explore the natural and cultural factors affecting human distribution, with the goal of providing insights for the conservation and development of ancient relics. We employed spatial analysis methods using ArcGIS 10.8 software, such as kernel density analysis and trend surface analysis, to analyse 1194 historical ancient sites listed in the National Cultural Relics Protection Units of China. The research findings are as follows: (1) the distribution of ancient sites demonstrates an agglomerative spatial pattern. The nearest neighbour index (R

How does government spending on environmental protection benefit people's health? The current paper analyzed 2010 and 2018 data from the China Family Panel Studies (CFPS) database to measure the impact of province-level environmental regulations on the health of local population. The study also applied the Alkire Foster method to develop the multidimensional health poverty (MHP) score, a new index intended to measure the health status of individuals in a holistic manner. Our results indicated that more fiscal spending on environmental regulation could improve health of the local population, especially among low-income population living in the rural areas. Further, the size of health benefit differs by the type of environmental regulation. More specifically, regulations focusing on preventing environmental pollution can achieve more sizable health benefits than remedial ones. Finally, fine inhalable particle (PM2.5) has the largest mediating effect on the relationship between environmental regulation and public health. These results provide several policy implications, which highlight the importance of: scaling up fiscal environmental expenditure and optimizing the structure of environmental expenditure with more emphasis on rural areas where more low-income population are located; shifting from ex-post accountability to ex-ante prevention; and strengthening regional cooperation in environmental protection among local governments, and establishing a cross-regional coordination mechanism.

Abstract The progression of chronic kidney diseases (CKD) is complex, influenced by a myriad of factors including gut microbiota. While emerging evidence suggests that gut microbiota can have beneficial effects in managing CKD, it is also recognized that dysbiosis may contribute to the progression of CKD and associated uremic complications. Our previous research has demonstrated the efficacy of lanthanum hydroxide in delaying kidney failure and preserving renal function. However, the role of lanthanum hydroxide in modulating gut microbiota in this context remains unclear. In our study, we induced CKD in rats using adenine, leading to gut microbial dysbiosis, kidney pathology, and disturbances in amino acid metabolism. In this adenine‐induced CKD model with hyperphosphatemia, treatment with lanthanum hydroxide improved renal function. This improvement was associated with the restoration of gut microbial balance and an increase in urine ammonium metabolism. These results suggest that the therapeutic potential of lanthanum hydroxide in CKD may be partly due to its ability to reshape gut microbiota composition. This study underscores the significance of lanthanum hydroxide in kidney protection, attributing its benefits to the modulation of gut microbiota in a rat model of CKD.

Prunella vulgaris is a traditional Chinese herbal medicine with many pharmacological effects, among which the anti-inflammatory effect is more significant. It is widely reported that Prunella vulgaris has anti-inflammatory, antioxidant, immune regulation, intestinal flora regulation and intestinal barrier protection effects on ulcerative colitis (UC). This paper collected relevant reports to further summarize the mechanisms and effective parts of Prunella vulgaris and its monomers in the treatment of UC and provided theoretical basis and reference for the application of Prunella vulgaris in UC.

Abstract Background Evaluating the efficacy of letrozole overlapped with gonadotropin-modified letrozole protocol (mLP) for diminished ovarian reserve (DOR) or advanced-age women with repeated cycles. Methods This is a retrospectively registered, paired-match study including 243 women with DOR and 249 women aged over 40 years old who received in vitro fertilization (IVF) treatment. 123 women received stimulation with mLP (mLP group). GnRH agonist (GnRH-a) long, GnRH antagonist (GnRH-anta), and mild stimulation protocol were used as controls with 123 women in each group. We further analyzed 50 of 123 patients in the mLP group who have experienced more than one failed cycles with other ovarian stimulation protocols (non-mLP group). Clinical pregnancy rate (CPR), cumulative clinical pregnancy rate (CCPR), and live birth rate (LBR) were main outcomes. Results The CPR in the mLP group (38.46%) was significantly higher than mild stimulation (17.11%), but not significantly different from GnRH-a long (26.13%) and GnRH-anta (29.17%) group. The CCPR showed an increasing trend in the mLP group (33.33%) although without significance when compared with controls. The CCRP of GnRH-a long, GnRH-anta, mild stimulation group were 21.68%, 29.03%, and 13.04%, respectively. In women with repeated cycles, mLP achieved the higher available embryo rate (P

Abstract Tumor is a representative of cell immortalization, while senescence irreversibly arrests cell proliferation. Although tumorigenesis and senescence seem contrary to each other, they have similar mechanisms in many aspects. Pancreatic ductal adenocarcinoma (PDA) is highly lethal disease, which occurs and progresses through a multi-step process. Senescence is prevalent in pancreatic premalignancy, as manifested by decreased cell proliferation and increased clearance of pre-malignant cells by immune system. However, the senescent microenvironment cooperates with multiple factors and significantly contributes to tumorigenesis. Evidently, PDA progression requires to evade the effects of cellular senescence. This review will focus on dual roles that senescence plays in PDA development and progression, the signaling effectors that critically regulate senescence in PDA, the identification and reactivation of molecular targets that control senescence program for the treatment of PDA.

BackgroundSenescence have emerged as potential factors of lung cancer risk based on findings from many studies. However, the underlying pathogenesis of lung cancer caused by senescence is not clear. In this study, we try to explain the potential pathogenesis between senescence and lung cancer through proteomics and metabonomics. And try to find new potential therapeutic targets in lung cancer patients through network mendelian randomization (MR).MethodsThe genome-wide association data of this study was mainly obtained from a meta-analysis and the Transdisciplinary Research in Cancer of the Lung Consortium (TRICL), respectively.And in this study, we mainly used genetic complementarity methods to explore the susceptibility of aging to lung cancer. Additionally, a mediation analysis was performed to explore the potential mediating role of proteomics and metabonomics, using a network MR design.ResultsGNOVA analysis revealed a shared genetic structure between HannumAge and lung cancer with a significant genetic correlation estimated at 0.141 and 0.135, respectively. MR analysis showed a relationship between HannumAge and lung cancer, regardless of smoking status. Furthermore, genetically predicted HannumAge was consistently associated with the proteins C-type lectin domain family 4 member D (CLEC4D) and Retinoic acid receptor responder protein 1 (RARR-1), indicating their potential role as mediators in the causal pathway.ConclusionHannumAge acceleration may increase the risk of lung cancer, some of which may be mediated by CLEC4D and RARR-1, suggestion that CLEC4D and RARR-1 may serve as potential drug targets for the treatment of lung cancer.

Summary: Non-natural nucleobase isocytosine (IC) is the isomer of cytosine; its chemical derivate 5-fluoroisocytosine (5-FIC) together with the isocytosine-specific deaminase (ICD) VCZ was suggested to be potential practical enzyme/prodrug pair for cancer therapy through gene-directed enzyme-prodrug therapy (GDEPT) method. In this study, we have determined the crystal structures of apo-VCZ and its complex with 5-FU. We identified the critical residues for substrate binding and catalytic reaction. We also captured the substrate-induced conformational changes of VCZ, then proposed the conjectural reaction procedures of VCZ for converting the IC into the uracil. Moreover, we evaluated the therapeutic effect of wildtype or the mutated VCZ protein in the colorectal cancer cell lines. Our studies will shed light on optimizing the ICD/5-FIC pairs by modifying either the enzyme or the prodrug based on the structural observations, thereby improving the possibility of applying the ICD/5-FIC pair in clinical trials.

Cancer is a serious disease with an abnormal proliferation of organ tissues; it is characterized by malignant infiltration and growth that affects human life. Traditional cancer therapies such as resection, radiotherapy and chemotherapy have a low cure rate and often cause irreversible damage to the body. In recent years, since the traditional treatment of cancer is still very far from perfect, researchers have begun to focus on non-invasive near-infrared (NIR)-responsive natural macromolecular hydrogel assembly drugs (NIR-NMHADs). Due to their unique biocompatibility and extremely high drug encapsulation, coupling with the spatiotemporal controllability of NIR, synergistic photothermal therapy (PTT), photothermal therapy (PDT), chemotherapy (CT) and immunotherapy (IT) has created excellent effects and good prospects for cancer treatment. In addition, some emerging bioengineering technologies can also improve the effectiveness of drug delivery systems. This review will discuss the properties of NIR light, the NIR-functional hydrogels commonly used in current research, the cancer therapy corresponding to the materials encapsulated in them and the bioengineering technology that can assist drug delivery systems. The review provides a constructive reference for the optimization of NIR-NMHAD experimental ideas and its application to human body.

ObjectiveAlzheimer’s disease (AD) as the most frequent neurodegenerative disease is featured by gradual decline of cognition and social function in the elderly. However, there have been few studies focusing on AD heterogeneity which exists both genetically and clinically, leading to the difficulties of AD researches. As one major kind of clinical heterogeneity, the lifespan of AD patients varies significantly. Aiming to investigate the potential driving factors, the current research identified the differentially expressed genes (DEGs) between longer-lived AD patients and shorter-lived ones via bioinformatics analyses.MethodsQualified datasets of gene expression profiles were identified in National Center of Biotechnology Information Gene Expression Omnibus (NCBI-GEO). The data of the temporal lobes of patients above 60 years old were used. Two groups were divided according to the lifespan: the group ≥85 years old and the group

As a natural ecological fragile region, the vast desert steppe in the Inner Mongolia has a developed animal husbandry, and thus posed great impacts on soil quality. In order to accurately evaluate the current situation of soil quality in the desert steppe, it is therefore imperative to adopt a suitable method to effectively assess the soil quality in the region. In this study, the minimum data set (MDS) was established with the help of principal component analysis, Norm value calculation, and correlation analysis, and four indicators, including organic matter, sand grains, soil erosion degree, and pH, were established to evaluate the soil quality of the desert steppe in the Siziwang Banner, a county in the Inner Mongolia. The results from the minimum data set (MDS) method were validated based on the total data set (TDS) method, and the validation indicated that the MDS method can be representative of the soil quality of the study area. The results indicated: 1) the soil quality index (SQI) of 0-30 cm in more than 90% of the study area falls in the range of 0.4 and 0.6 (medium level), while the better level (SQI ≥0.6) only accounted less than 10% of the study area; 2) For the MDS indexes, soil organic matter content at all depths decreased in the southern mountains, central hills, and northern plateau, which is consistent with the changing trends of SQI; 3) The sand grain was the dominant particle in the study region, which was in accordance with the intense wind erosion; 4) The negative correlation was found between the soil pH value and SQI (the high value in pH corresponded to the low value in SQI), which reflected that soil pH has a more stressful effect on the local vegetation. Overall, the MDS indexes in this study can objectively and practically reflect the soil quality in the study area, which can provide a cost effective method for SQI assessment in the desert steppe, which is important for the further grassland ecological construction and grassland management to improve the soil quality in the desert steppes.

The clustered regularly interspaced short palindromic repeats (CRISPR) system is a natural adaptive immune system of prokaryotes. The CRISPR-Cas system is currently divided into two classes and six types: types I, III, and IV in class 1 systems and types II, V, and VI in class 2 systems. Among the CRISPR-Cas type VI systems, the CRISPR/Cas13a system has been the most widely characterized for its application in molecular diagnostics, gene therapy, gene editing, and RNA imaging. Moreover, because of the trans-cleavage activity of Cas13a and the high specificity of its CRISPR RNA, the CRISPR/Cas13a system has enormous potential in the field of molecular diagnostics. Herein, we summarize the applications of the CRISPR/Cas13a system in the detection of pathogens, including viruses, bacteria, parasites, chlamydia, and fungus; biomarkers, such as microRNAs, lncRNAs, and circRNAs; and some non-nucleic acid targets, including proteins, ions, and methyl groups. Meanwhile, we highlight the working principles of some novel Cas13a-based detection methods, including the Specific High-Sensitivity Enzymatic Reporter UnLOCKing (SHERLOCK) and its improved versions, Cas13a-based nucleic acid amplification-free biosensors, and Cas13a-based biosensors for non-nucleic acid target detection. Finally, we focus on some issues that need to be solved and the development prospects of the CRISPR/Cas13a system.

Pseudouridine (Ψ) is one of the most abundant RNA modifications in cellular RNAs that post-transcriptionally impact many aspects of RNA. However, the metabolic fate of modified RNA nucleotides has long been a question. A pseudouridine kinase (PsuK) and a pseudouridine monophosphate glycosylase (PsuG) in Escherichia coli were first characterized as involved in pseudouridine degradation by catalyzing the phosphorylation of pseudouridine to pseudouridine 5′-phosphate (ΨMP) and further hydrolyzing 5′-ΨMP to produce uracil and ribose 5′-phosphate. Recently, their homolog proteins in eukaryotes were also identified, which were named PUKI and PUMY in Arabidopsis. Here, we solved the crystal structures of apo-EcPsuK and its binary complex with Ψ or N1-methyl-pseudouridine (m1Ψ). The structure of EcPsuK showed a homodimer conformation assembled by its β-thumb region. EcPsuK has an appropriate binding site with a series of hydrophilic and hydrophobic interactions for Ψ. Moreover, our complex structure of EcPsuK-m1Ψ suggested the binding pocket has an appropriate capacity for m1Ψ. We also identified the monovalent ion-binding site and potential ATP-binding site. Our studies improved the understanding of the mechanism of Ψ turnover.

ObjectiveInsulin resistance (IR) is an important determinant of the phenotype and morbidity of the polycystic ovary syndrome (PCOS). In this study, we aimed to figure out the association between the degree of menstrual disturbance and the severity of IR in women with PCOS.DesignIt is a cross-sectional study conducted in an academic tertiary setting.PatientsThe patients comprised five hundred twenty-seven women diagnosed with PCOS by the 2003 Rotterdam criteria and 565 controls with regular vaginal bleeding.InterventionsThe interventions done for this study are medical history collection, physical examination, and blood sampling.Main outcome measuresThe main outcome measures are body mass index (BMI), fasting glucose, fasting insulin, homeostatic model assessment for IR (HOMA-IR), and hormonal parameters.ResultsWomen with PCOS had a higher level of BMI, HOMA-IR, and HOMA-β than controls, with a decreased level of sex hormone-binding globulin and QUICK I index. The luteinizing hormone (LH)/follicle-stimulating hormone (FSH), testosterone (T), antral follicle count (AFC), dehydroepiandrosterone sulfate, free androgen index, modified Ferriman–Gallwey score, and the incidence of delayed insulin peak increased with the degree of menstrual disturbance, although there was no significance for the latter four parameters. Women with vaginal bleeding intervals of 45–90 days had a relatively higher level of HOMA-IR and HOMA-β, although it was adjusted with age and BMI than the other two groups. Similar results were observed in AUCI (area under the curve of insulin) and I/G [the ratio of AUCI and AUCG (area under the curve of glucose)]. Anovulatory women with vaginal bleeding episodes of less than 45 days tended to have higher glucose and insulin levels, area under the curve of glucose (AUCG), area under the curve of insulin (AUCI), HOMA-IR, and HOMA-β but decreased QUICK I and Matsuda index than those who were ovulatory. Women with vaginal bleeding intervals of longer than 45 days who had hyperandrogenism (HA) showed a higher level of glucose, insulin, HOMA-IR, and HOMA-β but lower QUICK I and Matsuda Index.ConclusionsIn women with PCOS, the severity of IR, the LH/FSH ratio, and androgen level increased with a higher degree of disturbance in menstrual cyclicity (i.e., the vaginal bleeding intervals). Subgroup analysis indicated that the situation of HA may aggravate the disorder of glucose metabolism in women with PCOS. Overall, the interval between episodes of vaginal bleeding may be useful as a ready measure for predicting the severity of IR in PCOS.

In this paper, under-directed topology, distributed coordinated tracking control schemes are proposed for multiple Euler-Lagrange systems with time-varying communication delays, nonlinear uncertainties, and external disturbances. Concerning with different leader velocities, both constant leader velocity case and time-varying leader velocity case are addressed by designing two different distributed observers. Combining with the proposed distributed leader velocity observers, two coordinated tracking control schemes are developed by the effort of neural network approximation and sliding mode technique, which can compensate the nonlinearities and uncertainties. For the first case, tracking errors are rigorously proved to be globally asymptotically converged by using Lyapunov-Krasovskii method. To further eliminate chattering caused by the discontinuous sign function, the saturation function is used for the second case, and the proposed control algorithm ensures the same convergence of tracking errors via Lyapunov analysis. Finally, the effectiveness of the proposed distributed tracking control schemes is verified by the numerical examples.

Accurate urban boundary data can directly reflect the expansion of urban space, help us accurately grasp the scale and form of urban space, and play a vital role in urban land development and policy-making. However, the lack of reliable multiscale and high-precision urban boundary data products and relevant training datasets has become one of the major factors hindering their application. The purpose of this study is to combine Sentinel-2 remote-sensing images and supplementary geographic data to generate a reliable high-precision urban boundary dataset for Henan Province (called HNUB2018). First, this study puts forward a clear definition of “urban boundary”. Using this concept as its basis, it proposes a set of operable urban boundary delimitation rules and technical processes. Then, based on Sentinel-2 remote-sensing images and supplementary geographic data, the urban boundaries of Henan Province are delimited by a visual interpretation method. Finally, the applicability of the dataset is verified by using a classical semantic segmentation deep learning model. The results show that (1) HNUB2018 has clear and rich detailed features as well as a detailed spatial structure of urban boundaries. The overall accuracy of HNUB2018 is 92.82% and the kappa coefficient reaches 0.8553, which is better than GUB (Henan) in overall accuracy. (2) HNUB2018 is well suited for deep learning, with excellent reliability and scientific validity. The research results of this paper can provide data support for studies of urban sprawl monitoring and territorial spatial planning, and will support the development of reliable datasets for fields such as intelligent mapping of urban boundaries, showing prospects and possibilities for wide application in urban research.

In this paper, we mainly investigate the coordinated tracking control issues of multiple Euler–Lagrange systems considering constant communication delays and output constraints. Firstly, we devise a distributed observer to ensure that every agent can get the information of the virtual leader. In order to handle uncertain problems, the neural network technique is adopted to estimate the unknown dynamics. Then, we utilize an asymmetric barrier Lyapunov function in the control design to guarantee the output errors satisfy the time-varying output constraints. Two distributed adaptive coordinated control schemes are proposed to guarantee that the followers can track the leader accurately. The first scheme makes the tracking errors between followers and leader be uniformly ultimately bounded, and the second scheme further improves the tracking accuracy. Finally, we utilize a group of manipulator networks simulation experiments to verify the validity of the proposed distributed control laws.

The mesoporous silicate molecular sieves were synthesized with polyether F127 as the template by the aerosol-assisted method for loading and release of ibuprofen (IBU). The synthesized samples were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction and N2 adsorption–desorption isotherms. The drug IBU was applied as a model drug to investigate the drug release behaviour by ultraviolet spectrophotometry measurements. The investigation results demonstrate that mesoporous silicate molecular sieves by the aerosol-assisted method are spherical with a core–shell structure. As the drug carrier, it has good structural stability and can achieve drug controlled release which is expected. It exhibits safety to a certain degree. Therefore, the aerosol-assisted synthesis method provides a new idea for the synthesis of sustained-release drug carriers.

A novel magnetic levitation support method is proposed, which can relieve the perturbation caused by traditional support methods and provide more accurate position control of the capsule. This method can keep the perfect symmetry of the octahedral spherical hohlraum and has the characteristics in stability, tunability and simplicity. It is also favorable that all the results, such as supporting forces acting on the superconducting capsule, are calculated analytically, and numerical simulations are performed to verify these results. A typical realistic design is proposed and discussed in detail. The superconducting coating material is suggested, and the required superconducting properties are listed. Damped oscillation of the floating capsule in thin helium gas is discussed, and the restoring time is estimated.

Extract of pine nodules (matsufushi) formed by bark proliferation on the surface of trees of Pinus tabulaeformis or Pinus massoniana has been used as an analgesic for joint pain, rheumatism, neuralgia, dysmenorrhea and other complaints in Chinese traditional medicine. Here we report the effects of matsufushi extract and its components on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. We found that matsufushi extract (0.0003–0.005%) and its component, SJ-2 (5-hydroxy-3-methoxy-trans-stilbene) (0.3–100 μM), but not the other three, concentration-dependently inhibited catecholamine secretion induced by acetylcholine, a physiological secretagogue. Matsufushi extract (0.0003–0.005%) and SJ-2 (0.3–100 μM) also inhibited 45Ca2+ influx induced by acetylcholine in a concentration-dependent manner, similar to its effect on catecholamine secretion. They also suppressed 14C-catecholamine synthesis and tyrosine hydroxylase activity induced by acetylcholine. In Xenopus oocytes expressing α3β4 nicotinic acetylcholine receptors, matsufushi extract (0.00003–0.001%) and SJ-2 (1–100 μM) directly inhibited the current evoked by acetylcholine. The present findings suggest that SJ-2, as well as matsufushi extract, inhibits acetylcholine-induced catecholamine secretion and synthesis by suppression of nicotinic acetylcholine receptor-ion channels in bovine adrenal medullary cells.

Macrophages are key immune system cells involved in inflammatory processes. Classically activated (M1) macrophages are characterized by strong antimicrobicidal properties, whereas alternatively activated (M2) macrophages are involved in wound healing. Severe inflammation can induce postoperative complications during the perioperative period. Invasive surgical procedures induce polarization to M1 macrophages and associated complications. As perioperative management, it is an important strategy to regulate polarization and functions of macrophages during inflammatory processes. Although propofol has been found to exhibit anti-inflammatory activities in monocytes and macrophages, it is unclear whether propofol regulates the functions of M1 and M2 macrophages during inflammatory processes. This study therefore investigated the effects of propofol on human macrophage polarization. During M1 polarization, propofol suppressed the production of IL-6 and IL-1β but did not affect TNF-α production. In contrast, propofol did not affect the gene expression of M2 markers, such as IL-10, TGF-β, and CD206, during M2 polarization. Propofol was similar to the GABAA agonist muscimol in inducing nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and inhibiting IL-6 and IL-1β, but not TNF-α, production. Knockdown of Nrf2 using siRNA significantly reduced the effect of propofol on IL-6 and IL-1β production. These results suggest that propofol prevents inflammatory responses during polarization of human M1 macrophages by suppressing the expression of IL-6 and IL-1β through the GABAA receptor and the Nrf2-mediated signal transduction pathway.

Highly crystalline mesoporous anatase TiO2 nanospheres with high surface area (higher than P25 and anatase TiO2) are prepared by a soft-template method. Despite the high specific surface area, these samples have three times lower equilibrium adsorption (

Soil wind erosion is one of the critical drivers of land degradation in the black soil region of northeastern China. In this study, 137Cs background value and soil wind erosion rate was studied by using 137Cs nuclide tracing technique in the black soil region of northeastern China, and wind erosion characteristics such as background value and soil erosion rate over the years were clarified, which has guiding significance for soil and water conservation and agricultural sustainable development in the black soil region of northeast China. The mean area activity of the Hilltop area was 1541 Bq·m-2, which was lower than the background value of 1879.7 Bq·m-2 in the study area. At the top of the hill, soil erosion occurred to some extent. The 137Cs profile has distributional characteristics that can be divided into three categories. Most of the 137Cs area activity in Hilltop area is evenly distributed in 0-15 cm, and the 137Cs area activity below 15 cm decreased gradually until it disappeared. The spatial difference of wind erosion rate is significant in the study area, mainly between 7.17-10.13 t·hm-2a-1. The average wind erosion rate of hilltops with different tillage quality depths has little difference. The average wind erosion rate is 8.60 t·hm-2a-1, which belongs to mild erosion. However, its erosion rate is higher than the tolerable soil loss of 2 t·hm-2a-1 in the black soil region of northeast China. As a result, soil erosion control in the black soil region of northeast China still requires attention. [ABSTRACT FROM AUTHOR]

Abstract Molecular features are incorporated into the integrated diagnostic system for adult diffuse gliomas. Of these, copy number variation (CNV) markers, including both arm‐level (1p/19q codeletion, +7/−10 signature) and gene‐level (EGFR gene amplification, CDKN2A/B homozygous deletion) changes, have revolutionized the diagnostic paradigm by updating the subtyping and grading schemes. Shallow whole genome sequencing (sWGS) has been widely used for CNV detection due to its cost‐effectiveness and versatility. However, the parallel detection of glioma‐associated CNV markers using sWGS has not been optimized in a clinical setting. Herein, we established a model‐based approach to classify the CNV status of glioma‐associated diagnostic markers with a single test. To enhance its clinical utility, we carried out hypothesis testing model‐based analysis through the estimation of copy ratio fluctuation level, which was implemented individually and independently and, thus, avoided the necessity for normal controls. Besides, the customization of required minimal tumor fraction (TF) was evaluated and recommended for each glioma‐associated marker to ensure robust classification. As a result, with 1× sequencing depth and 0.05 TF, arm‐level CNVs could be reliably detected with at least 99.5% sensitivity and specificity. For EGFR gene amplification and CDKN2A/B homozygous deletion, the corresponding TF limits were 0.15 and 0.45 to ensure the evaluation metrics were both higher than 97%. Furthermore, we applied the algorithm to an independent glioma cohort and observed the expected sample distribution and prognostic stratification patterns. In conclusion, we provide a clinically applicable algorithm to classify the CNV status of glioma‐associated markers in parallel.