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Hair colours, as a daily cosmetic used in ancient Chinese life, often appear in ancient Chinese medical books, according to types, and can be classified into herbal hair colours and mineral hair colours. Experimental reconstruction of herbal hair colours and mineral hair colours was carried out to explore the influence of factors such as the type and material of hair colours on the colouring effect. Meanwhile, the experiments were recorded and analysed using a stereo microscope. The experimental results show that the ancient hair colours are authentic and it is feasible that mineral hair colours and herbal hair colours are capable of colouring hair. Mineral hair colours have better colour fastness and colouring effects than herbal hair colours.

Awe could increase prosocial behavior, but little is known about its effects on interpersonal forgiveness. This study aims to explore the potential impact of awe on interpersonal forgiveness and the underlying mechanism of this process, using a combination of questionnaires, economic game and computational modeling. In Study 1, we utilized Trait Awe Scale (TAS) and Forgiveness Trait Scale (FTS) to examine the association between trait awe and trait forgiveness. In Study 2, we employed pre-screened video to induce awe, happy and neutral emotions, then evaluated the effects of induced awe on small-self and interpersonal forgiveness in hypothetical interpersonal offensive situations (Study 2a) and two economic interaction situations (Study 2b). Results from Study 1 indicate that there is a positive correlation between trait awe and trait forgiveness. Study 2 reveal that awe can enhance interpersonal forgiveness in both interpersonal conflict situations and economic interaction situations, and this effect is mediated by the sense of small-self elicited by awe. Overall, these findings contribute to our understanding of the potential impact of awe on interpersonal forgiveness and provide valuable insights into the mechanisms through which awe may influence forgiveness. Further research in this area could help to elucidate the potential applications of awe-based interventions in promoting forgiveness and positive social interactions.

Urban trees provide important ecosystem services to improve cities’ liveability and sustainability. Leaf chlorophyll content (Cab) estimation by remote sensing can help monitor tree health efficiently. However, the Cab retrieval of urban trees is challenging because of the complex canopy structures, backgrounds, and illuminations conditions. This paper proposed an automatic method for partitioning sunlit/shaded pixels and removal of bright-specular/dark-hole and background pixels. In addition, we proposed a new index, the Urban Tree Chlorophyll Index (UTCI), defined as UTCI=(ρ709-ρ697)/(ρ709-ρ686), based on the simulated hyperspectral images of urban tree using radiative transfer model. This proposed UTCI index outperforms existing narrow-band indices (NBIs) for estimating Cab for complex canopy structures, backgrounds, and illumination conditions evaluated using simulated hyperspectral images. The advantage of the UTCI was also demonstrated when applied to UAV hyperspectral images validated with direct field foliar measurements of Cab. It surpasses existing NBIs, demonstrating a moderate correlation (R2 = 0.34) with Cab under varying irradiance and a strong correlation (R2 = 0.62) with Cab under stable diffuse illumination. This study, for the first time, extensively investigated NBIs for Cab estimation of urban trees from UAV hyperspectral images, providing a theoretical and operational basis for future monitoring of Cab in the management of urban trees. This new method can be potentially applied to other vegetation types with complex canopy structures, backgrounds, and illuminations conditions.

BackgroundDiabetic skin wound is a complex problem due to the disruption of normal repairing program and lack of effective remedy. Lucilia sericata larvae (maggot) is a folk method to treat chronic skin wound, while its therapeutic effects on that caused by diabetic remains unknown.ObjectiveThis study aims to investigate the therapeutic effects of maggot extract (M.E.) on diabetic skin wound and its molecular mechanism by establishing the skin wound model of diabetic Sprague Dawley (SD) rats.MethodsDiabetic model was established by injecting intraperitoneally streptozotocin in SD rats under specific pathogen-free (SPF) conditions. The rat fasting blood glucose values were ≧16.7 mmol/L 72 hours after intraperitoneal streptozotocin (60mg/kg body weight) injection. The rats were divided into five groups (n = 10/group): normal group: normal SD rats without any treatment, diabetic blank group: the diabetic rats without any treatment, Vaseline group: the diabetic rats dressed with Vaseline, recombinant human epidermal-growth-factor (rhEGF) group: the diabetic rats dressed with a mixture of Vaseline and 200 μg/g rhEGF, M.E. group: the diabetic rats dressed with a mixture of Vaseline and 150 μg/ml maggot extract. The round open wounds (1.0 cm in diameter) down to the muscle fascia were made on both sides of rat dorsa by removing the skin layer (epidermis and dermis) and were daily photographed for calculating their healing rates. Hematoxylin-eosin (HE) and Masson's trichrome staining were performed on skin wound sections to analyze re-epithelialization and granulation tissue formation. Immunohistochemical (IHC), immunofluorescent (IF) stainings and Western blotting were conducted to analyze the statuses of STAT3 signaling.ResultsThe average wound healing rates on the 14th day were 91.7% in the normal, 79.6% in M.E., 71% in rhEGF, 55.1% in vaseline and 43.3% in the diabetes blank group. Morphological staining showed more active granulation tissue formation, re-epithelialization and neovascularization in M.E.-group than those in the blank and the vaseline-treated groups. Decreased p-STAT3 nuclear tranlocation and down-regulated Bcl-2, CyclinD1 and vascular endothelial growth factor (VEGF) expression were evidenced in the diabetic rats, which could be improved by rhEGF and especially M.E.ConclusionMaggot extract would be an alternative and/or adjuvant candidate for the better management of diabetic skin wounds because of its activity in enhancing STAT3 activation.

Synthetic aperture radar (SAR) records important information about the interaction of electromagnetic waves with the Earth’s surface. However, long-term and high-resolution backscatter coefficient data are still lacking in many urban studies (e.g., building height estimation). Here, we proposed a framework to reconstruct the 1-km backscatter coefficient in 1990–2022 utilizing the Sentinel-1 Ground Range Detected data and Landsat time series data in the Jing–Jin–Ji (JJJ) region. First, we developed a regression model to convert the optical signals from Landsat into backscatter coefficients as the Sentinel-1 data, using observations from 2015 to 2022. Then, we reconstructed backscatter coefficients from 1990 to 2022 using the long-term Landsat data. Using the reconstructed backscatter coefficients, we analyzed the dynamic patterns of building height over the past decades. The proposed approach performs well on estimating the backscatter coefficient and its spatial pattern, with the annual mean absolute error, root mean square error, and R2 of 1.10 dB, 1.50 dB, and 0.64, respectively. The temporal trends revealed from the reconstructed backscatter data are reliable compared with satellite observations at a relatively coarse resolution, with Pearson’s coefficients above 0.92 in 6 sample cities. The derived building height from the reconstructed SAR data indicates that the JJJ region experienced a noticeable upward expansion in 1990–2022, e.g., Beijing has the fastest growth rate of 0.420 km3/decade regarding the total building volumes. The proposed framework of reconstructing SAR data from optical satellite images provides a new insight to complement the long-term and high-resolution backscatter from local to global scales.

Purpose: Variant interpretation, guided by American College of Medical Genetics and Genomics guidelines, can inform clinical decision-making. However, interpretations may change over time for a variety of reasons. Periodic reanalysis of previous variant interpretations is important to ensure that reported genetic findings remain accurate according to current knowledge. Methods: We performed automated filtering by comparing ClinVar variants available in August 2020 with those from August 2021 to screen for potential reanalysis candidates from 3 projects. These variants were subsequently interpreted based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology variant interpretation guideline or ClinGen revised gene-specific guidelines if applicable. Results: Our method annotated 241 unique variants requiring reanalysis, from 3 projects containing 3,832,210 previously interpreted variants, including those filtered automatically. Among these 241 variants, 43 variants changed interpretation, including 55.81% (N = 24) with upgraded and 44.19% (N = 19) with downgraded classifications. An efficiency study showed that our strategy increased the reanalysis efficiency and saved reviewing time. Conclusion: We demonstrated an effective high-throughput method, initiating from external data updates, to achieve variant reanalysis in a clinical laboratory. This filtering method reduced the number of variants that need to be reanalyzed, screened potential variants, and saved time and cost for clinical laboratories.

Abstract Albeit nanozymes‐based tumor catalytic therapy (NCT) relies on endogenous chemical reactions that could achieve tumor microenvironment (TME)‐specialized reactive oxygen species (ROS) production, the unsatisfactory catalytic activity of nanozymes accompanied by complex TME poses a barrier to the therapeutic effect of NCT. Herein, a one‐step in situ synthesis strategy is reported to construct ternary Ru/TiO2−x@TiCN heterojunctions through oxidative conversion of TiCN nanosheets (NSs) to TiO2−x NSs and reductive deposition of Ru3+ to Ru nanoparticles. The narrow bandgap and existence of heterojunctions enhance the ultrasound‐activated ROS generation of Ru/TiO2−x@TiCN because of the accelerated electron transfer and inhibits electron–hole pair recombination. The augmented ROS production efficiency is achieved by Ru/TiO2−x@TiCN with triple enzyme‐like activities, which amplifies the ROS levels in a cascade manner through the catalytic decomposition of endogenous H2O2 to relieve hypoxia and heterojunction‐mediated NCT, as well as depletion of overexpressed glutathione. The satisfactory therapeutic effects of Ru/TiO2−x@TiCN heterojunctions are achieved through synergetic sonodynamic therapy and NCT, which achieve the complete elimination of tumors without recurrence. This strategy highlights the potential of in situ synthesis of semiconductor heterojunctions as enhanced sonosensitizers and nanozymes for efficient tumor therapy.

The FIFA World Cup, which represents the highest level in football, is regarded as a showcase to unfold the development trends of modern football, thus arousing great interest among researchers. However, most of the previous research designs studied the simple linear correlation between technical indicators and game outcomes, which may overlook the complex causalities in football performance. The aim of current study was to introduce a new method to examine winning patterns emerging from Qatar 2022 through a configurational lens. To this end, fuzzy-set qualitative comparative analysis (fsQCA) was conducted using 98 samples (n = 98) out of 49 Qatar 2022 matches discriminating winning and losing teams in regular time (group stage) and in 30 min of extra time (knockout stage). Then, we selected seven variables as our causal conditions, namely, shots on target, possession, defensive line breaks, crosses, receptions in the final third, forced turnovers, and direct pressures. Necessity analysis and sufficiency analysis of configurations were conducted according to fsQCA requirements. The fsQCA operation showed that no individual causal condition is necessary to winning a game and four configurations were derived from the QCA results and these combinations of conditions fall into three typologies of play style: a possession play style, direct play style, and all-round play style. The results confirmed the fact that football is a complex system and suggested that a winning outcome is often produced by combinations of multiple factors. The findings of the current study contribute to the literature by introducing the configurations of various technical and tactical indicators that could raise the possibility of winning and can be used by practitioners working within the fields of player development, coaching, and match preparation.

Carbon sinks in mangrove soils play a critical role in climate change mitigation globally. Soil dissolved organic matter (DOM) is a major form of labile organic matter and influences carbon cycling in wetland ecosystems. However, the factors regulating DOM pools in mangrove soils on a regional scale are not well understood. Here, we used a novel approach to assess soil DOM dynamics and its environmental drivers in mangrove wetlands on a national scale in China. Soil samples were collected from 43 sampling sites and distributed in mangroves across the coastline of China. DOM extracted from mangrove soils was characterized by fluorescence spectroscopy. We estimated that dissolved organic carbon (DOC) content ranged from 0.20 ± 0.02 g/kg to 3.85 ± 0.09 g/kg and nationally averaged 0.73 ± 0.07 g/kg in mangrove soils. Soil DOM was composed of humic-like substances, including humic acid-like (53.46 ± 8.74%) and fulvic acid-like (46.54 ± 8.74%). DOM pools in mangrove soils were identified to be perturbed by terrestrial inputs. Besides, the coupling interactions of environmental controls on the soil DOM pool were validated by establishing the structural equation modeling (SEM). We found that precipitation is the most important driver, which controlled directly the inputs and outputs of DOM pools. It also indirectly influenced DOM pools by regulating soil parameters through the cascade reactions. Cu, salinity, and clay are key mediators among soil parameters for precipitation affecting DOM pools. Precipitation influences soil DOC negatively and CDOM and FDOM positively markedly. The results provide novel insights into the labile carbon pool in mangrove soils and are beneficial for improving the assessment frameworks in the blue carbon ecosystems.

Background: Polychlorinated alkanes (PCAs) constitute a large group of individual congeners originating from commercial chlorinated paraffin (CP) products with carbon chain lengths of PCAs-C10-13, PCAs-C14-17, and PCAs-C18-32, occasionally containing PCAs-C6-9 impurities. The extensive use of CPs has led to global environmental pollution of PCAs. This study aimed to quantify PCAs in paired serum and breast milk of lactating Swedish mothers, exploring their concentration relationship. Methods: Twenty-five paired samples of mothers’ blood serum and breast milk were analysed and concentrations were determined for PCAs C6-32 and compared to 4,4′-DDE, the PCB congener 2,2′,4,4′,5,5′-hexachlorobiphenyl (CB-153), and hexachlorobenzene (HCB). Results: The median concentrations of PCAs-C6-9, PCAs-C10-13, PCAs-C14-17, PCAs-C18-32 and ΣPCAs in serum were 14, 790, 520, 16 and 1350 ng/g lipid weight (lw), respectively, and in breast milk 0.84, 36, 63, 6.0 and 107 ng/g lw. Levels of 4,4′-DDE, CB-153 and HCB were comparable in the two matrices, serum and breast milk at 17, 12 and 4.9 ng/g lw. The results show significant differences of PCAs-C10-13 and PCAs-C14-17 in breast milk with 22– and 6.2-times lower lw-based concentrations than those measured in serum. On wet weight the differences serum/breast milk ratios of PCAs-C6-9, PCAs-C10-13, PCAs-C14-17, PCAs-C18-32 and ΣPCAs were 1.7, 3.2, 1.0, 0.4 and 1.6, respectively, while the ratio for 4,4′-DDE, CB-153 and HCB were each close to 0.1. Conclusion: Swedish lactating mothers had high serum concentrations of PCAs-C10-13 and PCAs-C14-17, with the ΣPCAs median serum concentration of 1350 ng/g lw. The breast milk concentration, although considerably lower at 107 ng/g lw, still surpassed those of 4,4′-DDE, CB-153 and HCB, suggesting an exposure risk of infants to PCAs. The variation in blood and breast milk accumulation between PCAs and studied legacy POPs, is rarely discussed but warrants further studies on partitioning properties as well as associated toxicological implications.

Mangrove ecosystems play a critical role in supporting ecological service values and regulating the global carbon cycle. They have become one of the most highly vulnerable ecosystems in the Anthropocene under the long-term influence of diverse human perturbations. Soil dissolved organic matter (DOM) is an active fraction within the carbon cycle in mangrove ecosystems. However, it remains unclear how human perturbations regulate DOM dynamics. Here, we used the fluorescence method and structural equation modeling to quantify the anthropogenic and environmental influence on soil DOM across the urban development gradient on a national scale in China. Anthropogenic activities (urban construction and sewage discharge) and environmental factors (salinity, metals, pH, and soil organic carbon) were striking forces that shaped DOM quality in mangrove soils. Both indirect and direct effects played critical roles in the soil DOM heterogeneity across the gradient of urbanization. Environmental factors can act as cofactors mediating human impact on DOM pools and as promoters transforming soil DOM in mangroves. Our study provided novel insights into the relationship between coastal developments and mangrove soil DOM heterogeneity and improved knowledge of coastal ecosystems as blue carbon sinks.

Vat photopolymerization (VPP) is one of the convenient methods to create high-precision parts; however, due to the significant adhesion between the cured layer of the photopolymer resin and the release film, the currently prevalent VPP equipment is less productive and thus challenging in achieving production on a large scale. To tackle the issues above, a facile method is utilised to produce a transparent film capable of effectively resisting the photopolymer resin. Such film is achieved by incorporating micron-nanometre layered rough features and low surface energy materials onto the surface of quartz glass. It allows innovative applications in speedy VPP processes, achieving a printing speed of up to 323 mm/h in an LCD (Liquid Crystal Display) 3D printer while maintaining sound accuracy, exceptional durability and fair applicability, thanks to the features of the prepared film. The presented approach provides new perspectives into the production and application of VPP technology.

From the viewpoint of the poor formability and mechanical anisotropy of laser powder bed fusion (LPBF)-processed NiTi alloys, three different energy densities, i.e., minimum value, median value, and maximum value, were adopted in this work. The anisotropic behavior in the microstructural distribution and tensile properties were explored to evaluate the performance stability of NiTi components within a wide processing window. The results showed that an excellent deposition quality was acquired when the energy density was within the range of 45–75 J/mm3. The phase constitution and microstructural features were similar even under different processing parameters. In a single melting pool, the columnar grains within the body zone exhibited {110} and {100} textures. However, no preferred orientation was observed for the fine dot-like sub-structures within the overlapping zone. The anisotropy in tensile strength and plasticity was mainly attributed to the columnar grains with preferred crystallographic orientation in the body zone. Only a dimple-like morphology was observed on the fracture surface, indicating a ductile tensile failure mechanism. The findings demonstrated that the stable microstructural features and tensile performance of LPBF-processed NiTi components were ensured within a wide processing window (45–75 J/mm3), despite the anisotropic behavior along the transverse and longitudinal tensile directions.

The efficient design of Permanent Magnet Synchronous Motors (PMSMs) is crucial for their operational performance. A key design parameter, cogging torque, is significantly influenced by various structural parameters of the motor, complicating the optimization of motor structures. This paper proposes an optimization method for PMSM structures based on heuristic optimization algorithms, named the Permanent Magnet Synchronous Motor Self-Optimization Lift Algorithm (PMSM-SLA). Initially, a dataset capturing the efficiency of motors under various structural parameter scenarios is created using finite element simulation methods. Building on this dataset, a batch optimization solution aimed at PMSM structure optimization was introduced to identify the set of structural parameters that maximize motor efficiency. The approach presented in this study enhances the efficiency of optimizing PMSM structures, overcoming the limitations of traditional trial-and-error methods and supporting the industrial application of PMSM structural design.

Catnip (Nepeta cataria L.) plants produce a wide array of specialized metabolites with multiple applications for human health. The productivity of such metabolites, including nepetalactones, and natural insect repellents is influenced by the conditions under which the plants are cultivated. In this study, we assessed how field-grown catnip plants, transplanted after being propagated via either single-node stem cuttings or seeds, varied regarding their phytochemical composition throughout a growing season in two distinct environmental conditions (Pittstown and Upper Deerfield) in the state of New Jersey, United States. Iridoid terpenes were quantified in plant tissues via ultra-high-performance liquid chromatography with triple quadrupole mass spectrometry (UHPLC-QqQ-MS), and phenolic compounds (phenolic acids and flavonoids) were analyzed via UHPLC with diode-array detection (UHPLC-DAD). The highest contents of total nepetalactones in Pittstown were found at 6 weeks after transplanting (WAT) for both seedlings and cuttings (1305.4 and 1223.3 mg/100 g, respectively), while in Upper Deerfield, the highest contents for both propagules were at 11 WAT (1247.7 and 997.1 mg/100 g, respectively) for seed-propagated and stem cuttings). The highest concentration of nepetalactones was associated with floral-bud to partial-flowering stages. Because plants in Pittstown accumulated considerably more biomass than plants grown in Upper Deerfield, the difference in nepetalactone production per plant was striking, with peak productivity reaching only 598.9 mg per plant in Upper Deerfield and 1833.1 mg per plant in Pittstown. Phenolic acids accumulated in higher contents towards the end of the season in both locations, after a period of low precipitation, and flavone glycosides had similar accumulation patterns to nepetalactones. In both locations, rooted stem cuttings reached their maximum nepetalactone productivity, on average, four weeks later than seed-propagated plants, suggesting that seedlings have, overall, better agronomic performance.

Objective: To evaluate the performance of newly developed glycated hemoglobin (HbA1c) clinical analytic reagents and HPLC columns, applied on Tosoh HLC-723 G8 Analyzer. Methods: Newly developed reagents and columns were used on a Tosoh HLC-723 G8 Analyzer (standard mode) system to measure both of qulity contorls and the clinical blood samples to evaluate the performances of these newly developed prodcuts including precision, accuracy, linearity, carryover, bias evaluation, correlation with commercial reagents, and stability according to CLSI recommendations. Results: The CV of intra-assay precision and inter-assay precision of quality control and clinical blood sample assays using Lirimax products were both less than 3.00%. And the REs of accuracy were less than 6.00%. Linearity: R2 = 0.9993 in the concentration range 4.77%–14.67%. Carryover: 0.05%. The Bland-Altman mean difference: −0.003583% HbA1c (CI: 0.07398: −0.08115); Passing-Bablok regression: y = 1.0022(0.9984:1.006)x-0.01097(-0.03776: 0.01582), R2 = 0.9996. Stability evaluation was also acceptable. Conclusion: The performance of newly developed products was well evaluated for HbA1c measurement on a TOSOH G8 Analyzer which shows excellent suitability for clinical assay.

Triglycerides (TGs) in adipocytes provide the major stores of metabolic energy in the body. Optimal amounts of TG stores are desirable as insufficient capacity to store TG, as in lipodystrophy, or exceeding the capacity for storage, as in obesity, results in metabolic disease. We hypothesized that mice lacking TG storage in adipocytes would result in excess TG storage in cell types other than adipocytes and severe lipotoxicity accompanied by metabolic disease. To test this hypothesis, we selectively deleted both TG synthesis enzymes, DGAT1 and DGAT2, in adipocytes (ADGAT DKO mice). As expected with depleted energy stores, ADGAT DKO mice did not tolerate fasting well and, with prolonged fasting, entered torpor. However, ADGAT DKO mice were unexpectedly otherwise metabolically healthy and did not accumulate TGs ectopically or develop associated metabolic perturbations, even when fed a high-fat diet. The favorable metabolic phenotype resulted from activation of energy expenditure, in part via BAT (brown adipose tissue) activation and beiging of white adipose tissue. Thus, the ADGAT DKO mice provide a fascinating new model to study the coupling of metabolic energy storage to energy expenditure.

BackgroundHepatoblastoma (HB) is the most common liver tumor in children with easy metastasis. The emergence of ferroptosis as a novel form of cell death has gained increased attention in various human cancers. However, the roles of ferroptosis-related (FR) genes in HB remain elusiveMethodsThe GSE133039, GSE131329, and GSE81928 datasets were utilized for screening core FR genes in HB. Through Lasso regression analysis and using the support vector machine recursive feature elimination (SVM-RFE) algorithm, three candidate FR genes were obtained for characterizing HB. Their expression patterns and their clinical associations were explored through the ‘Limma’ R package, and their diagnostic potential was evaluated using ROC curves. Nitric oxide synthase 2 (NOS2) emerged as a candidate for further analyses. The CIBERSORT algorithm and GSEA dataset were used to respectively investigate the immune and metabolism effects of NOS2; the former was validated through immunofluorescence. The GSDC database was employed to analyze the correlation between NOS2 expression and the therapeutic efficacy of multiple drugs. PCR, Western blotting, colony formation assays, and Transwell experiments, were used to determine biological functions of NOS2 in HB cells. Potential upstream transcription factors of NOS2 were predicted through the TRRUST, hTFtarget, GeneCards, and JASPAR databases.ResultsNQO1, SLC1A4, and NOS2 were identified as potential genes in HB and found to be significantly upregulated in tumor samples. Nevertheless, only NOS2 was closely associated with HB clinicopathological characteristics; high NOS2 expression indicated poor prognosis, metastatic tendency, and late clinical stage. Immune analyses indicated that high NOS2 expression was concomitant with decreased infiltration levels of CD8+ T cells but increased infiltration levels of macrophages. GSEA revealed that NOS2 failed to affect the enrichments of glycolysis, fatty acid metabolism, and cholesterol biosynthesis in HB. Moreover, NOS2 was positively correlated with the IC50 values of trametinib, lapatinib, and cisplatin. NOS2 overexpression promoted the proliferation, migration and invasion of HepG2 and HuH-6 cells. JUND was identified as a potential transcriptional regulator of NOS2 by binding to its promoter (5’-TTCTGACTCTTTT-3’).ConclusionNOS2 plays a significant role in HB clinical assessments and holds promise as a novel therapeutic target.

Microbiome sequencing data normalization is crucial for eliminating technical bias and ensuring accurate downstream analysis. However, this process can be challenging due to the high frequency of zero counts in microbiome data. We propose a novel reference-based normalization method called normalization via rank similarity (RSim) that corrects sample-specific biases, even in the presence of many zero counts. Unlike other normalization methods, RSim does not require additional assumptions or treatments for the high prevalence of zero counts. This makes it robust and minimizes potential bias resulting from procedures that address zero counts, such as pseudo-counts. Our numerical experiments demonstrate that RSim reduces false discoveries, improves detection power, and reveals true biological signals in downstream tasks such as PCoA plotting, association analysis, and differential abundance analysis.

A novel design approach for broadening 3-dB axial ratio beamwidth (ARBW) of circular polarization (CP) patch antenna is herein introduced. A patch structure consisting of three pairs of slots and four coupled strips is firstly proposed and examined. In such a compact size of $0.216\,\,\lambda _{0} \times 0.216\,\,\lambda _{0} \times 0.013\,\,\lambda _{0}$ ( $\lambda _{0}$ is the free-space wavelength at the 2.42 GHz). By carefully studying the evolution and related impact of the patch structure, the ARBW broadening mechanism is thoroughly revealed. The far-zone fields are further studied by the theory of equivalent magnetic currents (EMCs), and two polarized degenerate modes TM10 and TM01 are generated to excite CP radiation. To better understand the working mechanism of the proposed parasitic structures, an equivalent circuit consisting of three networks is given. Finally, to validate the performance, the proposed antenna is fabricated and measured, the simulated and measured results of impedance bandwidth for $\vert \text{S}_{11}\vert \le -10$ dB is from 2.36 GHz to 2.48 GHz, and the measured 3-dB ARBW is 244° at plane $\varphi $ = 0°. Both simulated and measured results show that the proposed antenna is very promising for high elevation angle wireless applications.

Properties of cytidine and adenosine deaminases lead to off-target effects for cytosine base editors (CBEs) and adenine base editors (ABEs). Here the authors report that 25 TadA orthologs could be engineered to generate functional ABEs, CBEs or ACBEs via single/double mutations with minimised off-targets.

Hypercompact CRISPR-Cas12f systems have been engineered to generate miniABEs but these have limitations. Here the authors generate Cas12f-derived miniCBEs and develop miniABEs with improved editing and targeting scopes; they use these to correct pathogenic mutations in cell lines and introduce mutations in vivo.

Abstract Unmanned robotic systems are expected to liberate people from heavy, monotonous, and dangerous work. However, it is still difficult for robots to work in complicated environments and handle diverse tasks. To this end, a robotic system with four legs, four wheels, and a reconfigurable arm is designed. Special attention has been given to making the robot compact, agile, and versatile. Firstly, by using separate wheels and legs, it removes the coupling in the traditional wheeled–legged system and guarantees highly efficient locomotion in both the wheeled and legged modes. Secondly, a leg–arm reconfiguration design is adopted to extend the manipulation capability of the system, which not only reduces the total weight but also allows for dexterous manipulation and multi‐limb cooperation. Thirdly, a multi‐task control strategy based on variable configurations is proposed for the system, which greatly enhances the adaptability of the robot to complicated environments. Experimental results are given, which validate the effectiveness of the system in mobility and operation capability.

The rapid degradation of magnesium (Mg)-based implants in physiological environment limits its clinical applications, and alloying treatment is an effective way to regulate the degradation rate of Mg-based materials. In the present study, three Mg alloys, including Mg-0.8Ca (denoted as ZQ), Mg-0.8Ca-5Zn-1.5Ag (denoted as ZQ71) and Mg-0.8Ca-5Zn-2.5Ag (denoted as ZQ63), were fabricated by alloying with calcium (Ca), zinc (Zn) and silver (Ag). The results obtained from electrochemical corrosion tests and in vitro degradation evaluation demonstrated that the three Mg alloys exhibited distinct corrosion resistance, and ZQ71 exhibited the lowest degradation rate in vitro among them. After addition of Zn and Ag, the antibacterial potential of Mg alloys was also enhanced. The in vitro cell experiments showed that all the three Mg alloys had good biocompatibility. After implantation in a rat femoral defect, ZQ71 showed significantly higher osteogenic activity and bone substitution rate than ZQ63 and ZQ, due to its higher corrosion resistance as well as the stimulatory effects of the released metallic ions. In addition, the average daily degradation rate of each Mg alloy in vivo was significantly higher than that in vitro, as could be due to the implantation site located in the highly vascularized trabecular region. Importantly, the correlations between the in vitro and in vivo degradation parameters of the Mg alloys were systematically analyzed to find out the potential predictors of the in vivo degradation performance of the materials. The current work not only evaluated the clinical potential of the three biodegradable Mg alloys as bone grafts but also provided a feasible approach for predicting the in vivo degradation behavior of biodegradable materials.

Background: Circular RNAs (circRNAs) act as crucial regulators in tumorigenesis. In this study, the working mechanism of circ_0091579 in hepatocellular carcinoma (HCC) progression was investigated. Methods: The expression of RNA and protein was measured via RT-qPCR and Western blot assay. Cell proliferation ability was analyzed via CCK8, EdU and colony formation assays. Cell migration and invasion abilities were detected via transwell assays. Flow cytometry was applied to assess cell cycle and apoptosis. The target relation between miR-136-5p and circ_0091579 or tripartite motif containing 27 (TRIM27) was certified using dual-luciferase reporter assay. Xenograft tumor model was utilized to assess the role of circ_0091579 in tumor growth in vivo. The protein level of Ki67 in tumor tissues was analyzed by immunohistochemistry (IHC) assay. Results: Circ_0091579 expression was elevated in HCC tissues and cell lines. HCC patients with high circ_0091579 expression displayed low survival rate. Circ_0091579 knockdown suppressed the proliferation, migration, invasion, cell cycle progression and epithelial–mesenchymal transition (EMT) and induced apoptosis of HCC cells. Circ_0091579 acted as a molecular sponge for miR-136-5p, and circ_0091579 silencing-mediated effects were largely overturned by the knockdown of miR-136-5p in HCC cells. MiR-136-5p interacted with the 3′ untranslated region (3′UTR) of TRIM27, and TRIM27 overexpression largely counteracted miR-136-5p overexpression-induced influences in HCC cells. Circ_0091579 sponged miR-136-5p to up-regulate TRIM27 expression in HCC cells. Circ_0091579 silencing suppressed xenograft tumor growth in vivo. Conclusion: Circ_0091579 exhibited an oncogenic role to enhance the malignant potential of HCC cells through mediating miR-136-5p/TRIM27 axis in vitro and in vivo.

Abstract Objective Brain magnetic resonance imaging (MRI) findings in anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis are nonspecific and rarely have obvious associations with clinical characteristics and outcomes. This study aimed to comprehensively describe the MRI features of patients with NMDAR encephalitis, examine their associations with clinical characteristics, and evaluate their predictive power for disease recurrence and prognosis. Methods We retrospectively extracted the clinical data and brain MRI findings of 144 patients with NMDAR encephalitis. Patients underwent a 2‐year follow‐up to assess disease outcomes. We evaluated the associations of brain MRI findings at the onset with clinical characteristics, recurrence, and prognosis. Results Initial MRI showed typical abnormalities in 65 patients (45.1%); of these, 34 (29.3%) developed recurrence and 10 (9.4%) had poor prognosis (mRS ≥3). Binary logistic regression analyses revealed that insula abnormalities were associated with acute seizure (odds ratio [OR] = 3.048, 95% confidence interval [CI]: 1.026–9.060) and white matter lesions were associated with cognitive impairment (OR = 2.730, 95% CI: 1.096–6.799). Risk factors for a poor 2‐year prognosis included a higher number of brain MRI abnormalities (OR = 1.573, 95% CI: 1.129–2.192) and intensive care unit (ICU) admissions (OR = 15.312, 95% CI: 1.684–139.198). The risk factors for 2‐year recurrence included abnormalities of the thalamus (HR = 3.780, 95% CI: 1.642–8.699). Interpretations Brain MRI features of patients with NMDAR encephalitis were associated with clinical manifestations, prognosis, and recurrence. Higher numbers of MRI abnormalities and ICU admissions were predictive of poor prognosis. Abnormalities of the thalamus constituted a recurrence‐related risk factor.

Abstract Low back pain is common after lumbar spine surgery and the injury from extensive detachment of paraspinal muscles during the surgery may play a vital role. Previously, we prepared a bovine acellular tendon fiber (ATF) material through lyophilization and proved that it could retain its original fibrillar structure and mechanical properties. The objective of this study is to evaluate the effectiveness of this new fiber material used for attachment structure reconstruction of paraspinal muscle. Defect of spinous process, interspinous and supraspinous ligament was established on lumbar spine in rabbit and rat and ATF linear material was implanted to reconstruct the attachment structure. Ultrasound showed the cross-sectional area of the paraspinal muscle in ATF group was larger than that of control group in rats. MRI showed the irregular shape and high signal changes in control group, but regular shape and uniform signal in the ATF group in rabbit. For Electromyogram, the frequency of evoked potential in control group was lower than ATF group and normal rats. HE and Masson staining showed good tissue healing, and immunohistochemical results showed the immune rejection of ATF is significantly lower than that of suture. Reconstruction of the attachment structure of paraspinous muscles with ATF linear material could maintain the morphology, volume and function of paraspinal muscle. ATF material has the potential to be used to manufacture personalized ligaments and other tissue engineering scaffolds. Graphical abstract

Abstract Routing optimization is a well‐known and established topic with the fundamental goal of operating networks efficiently. Traditional optimization heuristics may suffer from performance penalty as it mismatches actual traffic, while artificial intelligence (AI) which has undergone a renaissance recently is gradually being applied to the network optimization and has shown excellent advantages. Especially deep reinforcement learning (DRL) is investigated as a key technology for routing optimization with the goal of enabling networks self‐driving. Therefore, we contributed in this paper a novel approach for practical intelligent routing method using DRL with GNN, which could be easily implemented as a northbound application on the SDN controller. Our method can not only output continuous control actions for routing optimization but also learn from some networks and generalize to other unseen ones. In order to emphasize the generalization and practicality of the intelligent routing method, we deploy it in a real SDN network for experimentation rather than simulation. The results show that the method can keep on optimizing the routing of traffic in other networks of different topologies after the training is stable. And compared with hop‐based OSPF, the optimal load‐balancing algorithm and the recent intelligent routing DROM, it reduces network delay by 16.1%, 19.6% and 14.3%, respectively, but at the expense of flow‐table space within the acceptable range.

The improved corrosion resistance, osteogenic activity, and antibacterial ability are the key factors for promoting the large-scale clinical application of magnesium (Mg)-based implants. In the present study, a novel nanocomposite coating composed of inner magnesium hydroxide, middle graphene oxide, and outer hydroxyapatite (Mg(OH)2/GO/HA) is constructed on the surface of Mg-0.8Ca–5Zn-1.5Ag by a combined strategy of hydrothermal treatment, electrophoretic deposition, and electrochemical deposition. The results of material characterization and electrochemical corrosion test showed that all the three coatings have high bonding strength, hydrophilicity and corrosion resistance. In vitro studies show that Mg(OH)2 indeed improves the antibacterial activity of the substrate. The next GO and GO/HA coating procedures both promote the osteogenic differentiation of MC3T3-E1 cells and show no harm to the antibacterial activity of Mg(OH)2 coating, but the latter exhibits the best promoting effect. In vivo studies demonstrate that the Mg alloy with the composite coating not only ameliorates osteolysis induced by bacterial invasion but also promotes bone regeneration under both normal and infected conditions. The current study provides a promising surface modification strategy for developing multifunctional Mg-based implants with good corrosion resistance, antibacterial ability and osteogenic activity to enlarge their biomedical applications.

While most bone defects can be repaired spontaneously, the healing process can be complicated due to insufficient bone regeneration when osteoporosis occurs. Synthetic materials that intrinsically stimulate bone formation without inclusion of exogenous cells or growth factors represent a highly desirable alternative to current grafting strategies for the management of osteoporotic defects. Herein, we developed a series of hydroxyapatite bioceramics composed of a microwhiskered scaffold (wHA) reinforced with multiple layers of releasable hydroxyapatite nanoparticles (nHA). These novel bioceramics (nwHA) are tunable to optimize the loading amount of nHA for osteoporotic bone formation. The utility of nwHA bioceramics for the proliferation or differentiation of osteoporotic osteoblasts in vitro is demonstrated. A much more compelling response is seen when bioceramics are implanted in critical-sized femur defects in osteoporotic rats, as nwHA bioceramics promote significantly higher bone regeneration and delay adjacent bone loss. Moreover, the nwHA bioceramics loaded with a moderate amount of nHA can induce new bone formation with a higher degree of ossification and homogenization. Two types of osteogenesis inside the nwHA bioceramic pores were discovered for the first time, depending on the direction of growth of the new bone. The current study recommends that these tailored hybrid micro/nanostructured bioceramics represent promising candidates for osteoporotic bone repair.

Given that apoptosis increases the risk of plaque rupture, strategies that reduce intracellular lipid levels without killing foam cells are warranted for safe and effective treatment of atherosclerosis. In this study, a mild phototherapy strategy is carried out to achieve the hypothesis. Foam cell-targeted nanoprobes that allow photothermal therapy (PTT) and/or photodynamic therapy (PDT) were prepared by loading hyaluronan and porphine onto black TiO2 nanoparticles. The results showed that when temperatures below 45 °C, PTT alone and PTT + PDT significantly reduced the intracellular lipid burden without inducing evidently apoptosis or necrosis. In contrast, the use of PDT alone resulted in only a slight reduction in lipid levels and induced massive apoptosis or necrosis. The protective effect against apoptosis or necrosis after mild-temperature PTT and PTT + PDT was correlated with the upregulation of heat shock protein 27. Further, mild-temperature PTT and PTT + PDT attenuated intracellular cholesterol biosynthesis and excess cholesterol uptake via the SREBP2/LDLR pathway, and also triggered ABCA1-mediated cholesterol efflux, ultimately inhibiting lipid accumulation in foam cells. Our results offer new insights into the mechanism of lipid regulation in foam cells and indicate that the black TiO2 nanoprobes could allow safer and more effective phototherapy of atherosclerosis.

Abstract Background Ossification of the posterior longitudinal ligament (OPLL) is a disabling disease whose pathogenesis is still unclear, and there are no effective cures or prevention methods. Exosomal miRNA plays an important role in the osteogenesis of ectopic bone. Therefore, we focused on the downregulation of miR-140-5p in OPLL cell-derived exosomes to explore the mechanism by which exosomal miR-140-5p inhibits osteogenesis in OPLL. Results Exosomes were isolated by differential centrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and exosomal markers. Exosomal RNA was extracted to perform miRNA sequencing and disclose the differentially expressed miRNAs, among which miR-140-5p was significantly downregulated. Confocal microscopy was used to trace the exosomal miR-140-5p delivered from OPLL cells to human mesenchymal stem cells (hMSCs). In vitro, we verified that exosomal miR-140-5p inhibited the osteoblast differentiation of hMSCs by targeting IGF1R and suppressing the phosphorylation of the IRS1/PI3K/Akt/mTOR pathway. In vivo, we verified that exosomal miR-140-5p inhibited ectopic bone formation in mice as assessed by micro-CT and immunohistochemistry. Conclusions We found that exosomal miR-140-5p could inhibit the osteogenic differentiation of hMSCs by targeting IGF1R and regulating the mTOR pathway, prompting a further potential means of drug treatment and a possible target for molecular therapy of OPLL.

Abstract Background The multiple de novo copy number variant (MdnCNV) phenotype is described by having four or more constitutional de novo CNVs (dnCNVs) arising independently throughout the human genome within one generation. It is a rare peri-zygotic mutational event, previously reported to be seen once in every 12,000 individuals referred for genome-wide chromosomal microarray analysis due to congenital abnormalities. These rare families provide a unique opportunity to understand the genetic factors of peri-zygotic genome instability and the impact of dnCNV on human diseases. Methods Chromosomal microarray analysis (CMA), array-based comparative genomic hybridization, short- and long-read genome sequencing (GS) were performed on the newly identified MdnCNV family to identify de novo mutations including dnCNVs, de novo single-nucleotide variants (dnSNVs), and indels. Short-read GS was performed on four previously published MdnCNV families for dnSNV analysis. Trio-based rare variant analysis was performed on the newly identified individual and four previously published MdnCNV families to identify potential genetic etiologies contributing to the peri-zygotic genomic instability. Lin semantic similarity scores informed quantitative human phenotype ontology analysis on three MdnCNV families to identify gene(s) driving or contributing to the clinical phenotype. Results In the newly identified MdnCNV case, we revealed eight de novo tandem duplications, each ~ 1 Mb, with microhomology at 6/8 breakpoint junctions. Enrichment of de novo single-nucleotide variants (SNV; 6/79) and de novo indels (1/12) was found within 4 Mb of the dnCNV genomic regions. An elevated post-zygotic SNV mutation rate was observed in MdnCNV families. Maternal rare variant analyses identified three genes in distinct families that may contribute to the MdnCNV phenomenon. Phenotype analysis suggests that gene(s) within dnCNV regions contribute to the observed proband phenotype in 3/3 cases. CNVs in two cases, a contiguous gene duplication encompassing PMP22 and RAI1 and another duplication affecting NSD1 and SMARCC2, contribute to the clinically observed phenotypic manifestations. Conclusions Characteristic features of dnCNVs reported here are consistent with a microhomology-mediated break-induced replication (MMBIR)-driven mechanism during the peri-zygotic period. Maternal genetic variants in DNA repair genes potentially contribute to peri-zygotic genomic instability. Variable phenotypic features were observed across a cohort of three MdnCNV probands, and computational quantitative phenotyping revealed that two out of three had evidence for the contribution of more than one genetic locus to the proband’s phenotype supporting the hypothesis of de novo multilocus pathogenic variation (MPV) in those families.

Glioma is the most common primary malignant intracranial tumor. Owing to highly aggressive invasiveness and metastatic properties, the prognosis of this disease remains poor even with surgery, radiotherapy, and chemotherapy. Rutin is a glycoside natural flavonoid that modulates microglia inflammatory profile and improves anti-glioma activity. Here, a glycoside flavonoid was extracted and named purple sweet potato delphinidin-3-rutin (PSPD3R). In an experiment using the subcutaneous xenograft model of human glioblastoma (GBM) and alamar blue assay, we found that PSPD3R suppressed the glioma proliferation both in vitro and in vivo. Flow cytometry assay and transmission electron microscopy observation revealed that PSPD3R stimulated glioma cell autophagy and apoptosis. High-throughput microRNA (miRNA) sequencing showed that PSPD3R substantially affected the miRNA expression of U251 cells. Acridine orange staining and immunoblotting indicated that PSPD3R regulated autophagy via Akt/Creb/miR-20b-5p in glioma cells. Luciferase reporter assays showed that autophagy-related gene 7 (Atg7) mRNA was the target gene of miR-20b-5p. The downregulation of miR-20b-5p inhibited glioma proliferation in vivo. In summary, PSPD3R regulated autophagy in glioma via the Akt/Creb/miR-20b-5p/Atg7 axis. This work unraveled the molecular mechanism of PSPD3R-induced autophagy in glioma and revealed its potential as a therapeutic agent for glioma treatment.

The fast development of biomaterials science and engineering has generated significant number of studies and publications as well as tremendous amount of research data. A methodology is needed to translate such research data and results to validated scientific evidence. This article for the first time proposes the concept and methodology of evidence-based biomaterials research, which is to use evidence-based research approach represented by systematic reviews to generate evidence for answering scientific questions related to biomaterials. After briefly introducing the advancement of biomaterials since 1950s, the scientific and engineering nature of biomaterials are discussed along with the roadmap of biomaterials translation from basic research to commercialized medical products, and the needs of scientific evidence. Key information of the evidence-based approach such as its origination from evidence-based medicine, levels of evidence, systematic review and meta-analysis, differences between systematic and narrative reviews is then highlighted. Applications with a step-by-step procedure of conducting evidence-based biomaterials research, three examples of biomaterials research using evidence-based approach to generate scientific evidence, and opportunities and challenges of evidence-based biomaterials research are presented. With its notable impact on the practice of medicine, the evidence-based approach is also expected to make influential contributions to the biomaterials field.

Equi-atomic NiTi shape memory alloy (SMA) samples were manufactured by selective laser melting (SLM) with different laser volume energy densities via synchronously varying laser power and scanning speed. The processing quality, phase transformation, and microstructural evolution were investigated to explore the mechanisms that are responsible for mechanical and functional properties. The results showed scattered micro-sized spherical gaseous defects inside the deposit. One-stage phase transformation occurred without intermediate R-phase transition, and the temperature of both endothermic and exothermic peaks was lower than that of the ingot. The microstructure initially grew along the building direction, but displayed different crystal orientations between coarse columnar grains and refined irregular sub-grains. The micro-hardness mapping revealed that homogenous anti-indentation properties were acquired independent of location variations. While the anisotropic behavior in tensile properties occurred due to the passive effect of columnar B2 austenitic grains, a synergistic effect of strength and plasticity was acquired primarily due to the combined effect of sub-grain refinement strengthening and transformation-induced plasticity. The pre-deformed NiTi samples recovered to their original shape when heated above its critical phase transition point. This work demonstrated that the crack-free NiTi SMA with exceptional comprehensive performances could be fabricated by SLM through the control of energy density.

Abstract Background In medical genetics, discovery and characterization of disease trait contributory genes and alleles depends on genetic reasoning, study design, and patient ascertainment; we suggest a segmental haploid genetics approach to enhance gene discovery and molecular diagnostics. Methods We constructed a genome-wide map for nonallelic homologous recombination (NAHR)-mediated recurrent genomic deletions and used this map to estimate population frequencies of NAHR deletions based on large-scale population cohorts and region-specific studies. We calculated recessive disease carrier burden using high-quality pathogenic or likely pathogenic variants from ClinVar and gnomAD. We developed a NIRD (NAHR deletion Impact to Recessive Disease) score for recessive disorders by quantifying the contribution of NAHR deletion to the overall allele load that enumerated all pairwise combinations of disease-causing alleles; we used a Punnett square approach based on an assumption of random mating. Literature mining was conducted to identify all reported patients with defects in a gene with a high NIRD score; meta-analysis was performed on these patients to estimate the representation of NAHR deletions in recessive traits from contemporary human genomics studies. Retrospective analyses of extant clinical exome sequencing (cES) were performed for novel rare recessive disease trait gene and allele discovery from individuals with NAHR deletions. Results We present novel genomic insights regarding the genome-wide impact of NAHR recurrent segmental variants on recessive disease burden; we demonstrate the utility of NAHR recurrent deletions to enhance discovery in the challenging context of autosomal recessive (AR) traits and biallelic variation. Computational results demonstrate new mutations mediated by NAHR, involving recurrent deletions at 30 genomic regions, likely drive recessive disease burden for over 74% of loci within these segmental deletions or at least 2% of loci genome-wide. Meta-analyses on 170 literature-reported patients implicate that NAHR deletions are depleted from the ascertained pool of AR trait alleles. Exome reanalysis of personal genomes from subjects harboring recurrent deletions uncovered new disease-contributing variants in genes including COX10, ERCC6, PRRT2, and OTUD7A. Conclusions Our results demonstrate that genomic sequencing of personal genomes with NAHR deletions could dramatically improve allele and gene discovery and enhance clinical molecular diagnosis. Moreover, results suggest NAHR events could potentially enable human haploid genetic screens as an approach to experimental inquiry into disease biology.

Background TP53, the most mutated gene in solid cancers, has a profound impact on most hallmarks of cancer. Somatic TP53 mutations occur in high frequencies in head and neck cancers, including oral squamous cell carcinoma (OSCC). Our study aims to understand the role of TP53 gain-of-function mutation in modulating the tumor immune microenvironment (TIME) in OSCC.Methods Short hairpin RNA knockdown of mutant p53R172H in syngeneic oral tumors demonstrated changes in tumor growth between immunocompetent and immunodeficient mice. HTG EdgeSeq targeted messenger RNA sequencing was used to analyze cytokine and immune cell markers in tumors with inactivated mutant p53R172H. Flow cytometry and multiplex immunofluorescence (mIF) confirmed the role of mutant p53R172H in the TIME. The gene expression of patients with OSCC was analyzed by CIBERSORT and mIF was used to validate the immune landscape at the protein level.Results Mutant p53R172H contributes to a cytokine transcriptome network that inhibits the infiltration of cytotoxic CD8+ T cells and promotes intratumoral recruitment of regulatory T cells and M2 macrophages. Moreover, p53R172H also regulates the spatial distribution of immunocyte populations, and their distribution between central and peripheral intratumoral locations. Interestingly, p53R172H-mutated tumors are infiltrated with CD8+ and CD4+ T cells expressing programmed cell death protein 1, and these tumors responded to immune checkpoint inhibitor and stimulator of interferon gene 1 agonist therapy. CIBERSORT analysis of human OSCC samples revealed associations between immune cell populations and the TP53R175H mutation, which paralleled the findings from our syngeneic mouse tumor model.Conclusions These findings demonstrate that syngeneic tumors bearing the TP53R172H gain-of-function mutation modulate the TIME to evade tumor immunity, leading to tumor progression and decreased survival.

BackgroundThe mechanisms of hypertrophic scar formation and its tissue inflammation remain unknown.MethodsWe collected 33 hypertrophic scar (HS) and 36 normal skin (NS) tissues, and detected the tissue inflammation and bacteria using HE staining, Gram staining, and transmission electronic microscopy (TEM), in situ hybridization and immunohistochemistry for MCP-1, TNF-α, IL-6 and IL-8. In addition, the samples were assayed by 16S rRNA sequencing to investigate the microbiota diversity in HS, and the correlation between the microbiota and the indices of Vancouver Scar Scale(VSS)score.ResultsHE staining showed that a dramatically increased number of inflammatory cells accumulated in HS compared with NS, and an enhanced number of bacteria colonies was found in HS by Gram staining, even individual bacteria could be clearly observed by TEM. In situ hybridization demonstrated that the bacteria and inflammation cells co-localized in the HS tissues, and immunohistochemistry indicated the expression of MCP-1, TNF-α, IL-6, and IL-8 were significantly upregulated in HS than that in NS. In addition, there was a significantly different microbiota composition between HS and NS. At the phylum level, Firmicutes was significantly higher in HS than NS. At the genus level, S. aureus was the dominant species, which was significantly higher in HS than NS, and was strongly correlated with VSS indices.ConclusionMicrobiome dysbiosis, dominated by S. aureus, occurred in HS formation, which is correlated with chronic inflammation and scar formation, targeting the microbiome dysbiosis is perhaps a supplementary way for future scar management.

IntroductionBiological soil crusts (BSCs) are distributed in arid and semiarid regions, and they function as important microhabitats for nitrogen fixation. The diazotroph community is critical for nitrogen fixation in BSCs and their subsoils. However, little is known about the key groups in different types of BSCs and subsoils in temperate semi-arid or arid deserts.MethodsHere, we sampled three types of BSCs and their subsoils from the Inner Mongolian plateau, investigated the distribution characteristics of the diazotroph community by high-throughput sequencing, predicted keystone species using the molecular ecological network analyses pipeline (MENAP), and verified their close relationship with the available nitrogen (AN) content.ResultsThe results showed that available nitrogen content in BSCs was higher than that in subsoils in three different types of BSCs, and there were differences among seasons and according to the mean annual precipitation. The abundance of diazotrophs was higher in Cyano-BSCs, while diversity had no significant difference among BSCs and subsoils. Cyanobacteria and Proteobacteria, Nostocaceae and Scytonemataceae, Skermanella, Scytonema, Azohydromonas, Nostoc and Trichormus were the dominant phyla, families, and genera, respectively. The dominant groups belong to Skermanella, Scytonema, and Nostoc formed the core diazotroph community in the three types of BSCs and subsoils, and each had a close relationship with AN.DiscussionThese results indicate that diazotrophs in BSCs and subsoils had high diversity, and the core diazotroph communities have a close relationship with nitrogen fixation and that they may be the main contributor to nitrogen fixing in BSCs and subsoils in temperate deserts.

The correlation of guided wave propagation characteristics with structural prestress is of paramount importance to the structural health monitoring of gas pipelines. A variable section structure and inhomogeneous prestress are common conditions in the pipeline. However, most of the existing guided wave finite element models focus on the structure size and stress distribution under two-dimensional conditions, and it is difficult to analyze the three-dimensional structure with non-uniform stress and variable cross section. In this paper, an acoustoelastic theory combined with a semi-analytical finite element based on the three-dimensional mapping method is proposed to investigate guided wave propagation. It provides a generalized tool to study guided waves in waveguides with a variable cross section under inhomogeneous prestress. Then it is applied to two cases, a hollow cylinder with a variable cross section subjected to axial force and radial force, to demonstrate the capability of the method. Dispersive solutions are obtained in terms of the three-dimensional dispersion surface and the change in phase velocity in a variable cross section. The results show that there is a propagation mode, which is insensitive to the change in the section but sensitive to the change in prestress. The effectiveness of the proposed method is verified by comparing with the experimental results. This study provides a good application prospect for the structural design and performance analysis of variable cross section waveguides.

The conflict between the human-environment is more prominent in densely populated areas (DPA) where urban expansion is increasingly disturbing the ecological environment, resulting in significant damage to habitat quality (HQ). However, a few studies have examined the impacts of urban expansion on HQ in the DPA under different scenarios, especailly in the Yellow River Basin. Therefore, we quantitatively analyzed the impacts of urban expansion on HQ from 1990 to 2018 by coupling the FLUS-InVEST model and predicted the changes of urban expansion and HQ by 2030. The results showed that: (1) the urban expansion rate of DPA was 46.4%. Among them, Hohhot-Baotou-Ordos-Yulin (HBOY) urban agglomeration expanded at the highest rate, with an expansion intensity of 0.16%. The urban expansion pattern was mainly edge expansion. (2) The overall HQ decreased by 1.6%. The HQ patch level was affected by urban expansion, and the higher-level habitat patches were easily shifted to lower-level habitat patches. Low HQ patches increased by 38.6% while high HQ gradually decreased. (3) Under the natural development scenario, the rate of urban expansion was 28.9% and HQ decreased by 2.9%. However, HQ only descesaed by 0.8% under HQ constraint scenario, indicating that urban expansion in a constrained way is of great benefit to improve HQ. These results provide a reference for ecological conservation and sustainable development in DPA.

Background: Uveal Melanoma (UM) is the most prevalent primary intraocular malignancy in adults. This study assessed the importance of chromatin regulators (CRs) in UM and developed a model to predict UM prognosis.Methods: Gene expression data and clinical information for UM were obtained from public databases. Samples were typed according to the gene expression of CRs associated with UM prognosis. The prognostic key genes were further screened by the protein interaction network, and the risk model was to predict UM prognosis using the least absolute shrinkage and selection operator (LASSO) regression analysis and performed a test of the risk mode. In addition, we performed gene set variation analysis, tumor microenvironment, and tumor immune analysis between subtypes and risk groups to explore the mechanisms influencing the development of UM.Results: We constructed a signature model consisting of three CRs (RUVBL1, SIRT3, and SMARCD3), which was shown to be accurate, and valid for predicting prognostic outcomes in UM. Higher immune cell infiltration in poor prognostic subtypes and risk groups. The Tumor immune analysis and Tumor Immune Dysfunction and Exclusion (TIDE) score provided a basis for clinical immunotherapy in UM.Conclusion: The risk model has prognostic value for UM survival and provides new insights into the treatment of UM.

Neurovascular imaging is essential for investigating neurodegenerative diseases. However, the existing neurovascular imaging technology suffers from a trade-off between a field of view (FOV) and resolution in the whole brain, resulting in an inhomogeneous resolution and lack of information. Here, homogeneous-resolution arched-scanning photoacoustic microscopy (AS-PAM), which has an ultrawide FOV to cover the entire mouse cerebral cortex, was developed. Imaging of the neurovasculature was performed with a homogenous resolution of 6.9 µm from the superior sagittal sinus to the middle cerebral artery and caudal rhinal vein in an FOV of 12 × 12 mm2. Moreover, using AS-PAM, vascular features of the meninges and cortex were quantified in early Alzheimer’s disease (AD) and wild-type (WT) mice. The results demonstrated high sensitivity to the pathological progression of AD on tortuosity and branch index. The high-fidelity imaging capability in large FOV enables AS-PAM to be a promising tool for precise brain neurovascular visualization and quantification.

Abstract As the number of devices connected to the Internet of Things (IoT) increases significantly, it leads to an exponential growth in the number of services that need to be processed and stored in the large-scale Cloud-based service repositories. An efficient service indexing model is critical for service retrieval and management of large-scale Cloud-based service repositories. The multilevel index model is the state-of-art service indexing model in recent years to improve service discovery and combination. This paper aims to optimize the model to consider the impact of unequal appearing probability of service retrieval request parameters and service input parameters on service retrieval and service addition operations. The least-used key selection method has been proposed to narrow the search scope of service retrieval and reduce its time. The experimental results show that the proposed least-used key selection method improves the service retrieval efficiency significantly compared with the designated key selection method in the case of the unequal appearing probability of parameters in service retrieval requests under three indexing models.

Oral squamous cell carcinoma models are presented with defined Trp53 mutations associated with immune checkpoint inhibitor responsiveness, e.g. T122N amino acid change of Tp53 promotes a cold TME enriched with immunosuppressive M2 macrophages resistant to ICI therapy.

Cloud data centers have become overwhelmed with data-intensive applications due to the limited computational capabilities of mobile terminals. Mobile edge computing is emerging as a potential paradigm to host application execution at the edge of networks to reduce transmission delays. Compute nodes are usually distributed in edge environments, enabling crucially efficient task scheduling among those nodes to achieve reduced processing time. Moreover, it is imperative to conserve edge server energy, enhancing their lifetimes. To this end, this paper proposes a novel task scheduling algorithm named Energy-aware Double-fitness Particle Swarm Optimization (EA-DFPSO) that is based on an improved particle swarm optimization algorithm for achieving energy efficiency in an edge computing environment along with minimal task execution time. The proposed EA-DFPSO algorithm applies a dual fitness function to search for an optimal tasks-scheduling scheme for saving edge server energy while maintaining service quality for tasks. Extensive experimentation demonstrates that our proposed EA-DFPSO algorithm outperforms the existing traditional scheduling algorithms to achieve reduced task completion time and conserve energy in an edge computing environment.

Abstract Background The contribution of autophagy to cancer therapy resistance remains complex, mainly owing to the discrepancy of autophagy mechanisms in different therapy. However, the potential mechanisms of autophagy-mediated resistance to icotinib have yet to be elucidated. Methods The effect of autophagy in icotinib resistance was examined using a series of in vitro and in vivo assays. The results above were further verified in biopsy specimens of lung cancer patients before and after icotinib or gefitinib treatment. Results Icotinib increased ATG3, ATG5, and ATG7 expression, but without affecting Beclin-1, VPS34 and ATBG14 levels in icotinib-resistant lung cancer cells. Autophagy blockade by 3-MA or silencing Beclin-1 had no effects on resistance to icotinib. CQ effectively restored lung cancer cell sensitivity to icotinib in vitro and in vivo. Notably, aberrantly activated STAT3 and highly expressed FOXM1 were required for autophagy induced by icotinib, without the involvement of AMPK/mTOR pathway in this process. Alterations of STAT3 activity using genetic and/or pharmacological methods effectively affected FOXM1 and ATG7 levels increased by icotinib, with altering autophagy and icotinib-mediated apoptosis in resistant cells. Furthermore, silencing FOXM1 impaired up-regulated ATG7 induced by STAT3-CA and icotinib. STAT3/FOXM1 signalling blockade also reversed resistance to icotinib in vivo. Finally, we found a negative correlation between STAT3/FOXM1/ATG7 signalling activity and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) treatment efficacy in patients undergoing EGFR-TKIs treatment. Conclusions Our findings support that STAT3/FOXM1/ATG7 signalling-induced autophagy is a novel mechanism of resistance to icotinib, and provide insights into potential clinical values of ATG7-dependent autophagy in icotinib treatment. Graphical abstract