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Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist with favorable effects on fatty and glucose metabolism, has been considered the leading candidate drug for nonalcoholic steatohepatitis (NASH) treatment. However, its limited effectiveness in resolving liver fibrosis and lipotoxicity-induced cell death remains a major drawback. Ferroptosis, a newly recognized form of cell death characterized by uncontrolled lipid peroxidation, is involved in the progression of NASH. Nitric oxide (NO) is a versatile biological molecule that can degrade extracellular matrix. In this study, we developed a PEGylated thiolated hollow mesoporous silica nanoparticles (MSN) loaded with OCA, as well as a ferroptosis inhibitor liproxsatin-1 and a NO donor S-nitrosothiol (ONL@MSN). Biochemical analyses, histology, multiplexed flow cytometry, bulk-tissue RNA sequencing, and fecal 16S ribosomal RNA sequencing were utilized to evaluate the effects of the combined nanoparticle (ONL@MSN) in a mouse NASH model. Compared with the OCA-loaded nanoparticles (O@MSN), ONL@MSN not only protected against hepatic steatosis but also greatly ameliorated fibrosis and ferroptosis. ONL@MSN also displayed enhanced therapeutic actions on the maintenance of intrahepatic macrophages/monocytes homeostasis, inhibition of immune response/lipid peroxidation, and correction of microbiota dysbiosis. These findings present a promising synergistic nanotherapeutic strategy for the treatment of NASH by simultaneously targeting FXR, ferroptosis, and fibrosis.

In order to improve the ability of cooperative spectrum sensing to withstand spectrum sensing data falsification (SSDF) attacks, a double reputation and multi-angle weight-based cooperative spectrum sensing (DRMW-CSS) method was proposed.Firstly, a scoring reputation was obtained by multiple iterations of historical local decision results, and an accuracy reputation was calculated on this basis.Secondly, secondary users (SU) were screened by double reputation and multiple reputation thresholds.Then, the impact of SSDF attacks on the screening method was judged and divided into three situations.Finally, the final global decision was made using the corresponding multi-angle weight data fusion decision method according to different situations.Simulation results show that the proposed method has good sensing accuracy when facing SSDF attacks with different attack strategies and probabilities, and has better anti-attack capability compared to traditional methods.

In order to support the implementation of “multidimensional orthogonal configured communication protection between communication modules as well as parameters and interference” in cognitive communication countermeasures scenarios, jamming effectiveness requires module level responsiveness.A penetrating jamming effectiveness evaluation method was proposed.Firstly, the core parameters of each signal processing module were selected as evaluation parameters.Secondly, analytic hierarchy process (AHP) and entropy weight method (EWM) were used to determine the weight of indicators.The coordination problem in AHP was solved through expert weight allocation, and the weight allocation problem in EWM was solved through non-uniform mapping.Finally, the subjective and objective weights were weighed through game theory, and the jamming effectiveness was judged by the technique for order preference by similarity to ideal solution (TOPSIS).By conducting evaluation experiments on the jamming performance of the Link16 data link, taking into account multiple aspects such as jamming types, number of jamming frequencies, jamming duration, and system types.Experiment results demonstrate that the penetration-based jamming performance evaluation method not only provides a more intuitive representation of the relationship between evaluation results and metric parameters, but also possesses excellent jamming discrimination capability.

Abstract Objective To investigate the association between metabolic syndrome (MetS) and its components and the risk of developing urologic cancers. Methods This study included 101,510 observation subjects from May 2006 to December 2007. The subjects received questionnaires and were subjected to clinical and laboratory examinations to collect data on baseline population characteristics, waist circumference (WC), blood pressure (BP), blood glucose, blood lipids, lifestyle, and past disease history. Finally, follow-up was conducted from the date of recruitment to December 31, 2019. Cox proportional hazards modelling was applied to analyze the association between MetS and its components and the risk of developing urologic cancers. Results A total of 97,975 observation subjects met the inclusion criteria. The cumulative follow-up period included 1,209,178.65 person-years, and the median follow-up time was 13.03 years. During the follow-up period, 485 cases of urologic cancers (165 cases of kidney cancer, 134 cases of prostate cancer, 158 cases of bladder cancer, and 28 cases of other urologic cancers) were diagnosed. The log-rank test results for the cumulative incidences of urologic cancer, kidney cancer, and prostate cancer indicated significant (P

Overexpression of SNCA has been implicated in the pathogenesis of synucleinopathies, particularly Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). While PD and DLB share some clinical and pathological similarities, each disease presents distinct characteristics, including the primary affected brain region and neuronal type. We aimed to develop neuronal-type-specific SNCA-targeted epigenome therapies for synucleinopathies. The system is based on an all-in-one lentiviral vector comprised of CRISPR-dSaCas9 and guide RNA (gRNA) targeted at SNCA intron 1 fused with a synthetic repressor molecule of Krüppel-associated box (KRAB)/ methyl CpG binding protein 2 (MeCp2) transcription repression domain (TRD). To achieve neuronal-type specificity for dopaminergic and cholinergic neurons, the system was driven by tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) promoters, respectively. Delivering the system into human induced pluripotent stem cell (hiPSC)-derived dopaminergic and cholinergic neurons from a patient with the SNCA triplication resulted in efficient and neuronal-type-specific downregulation of SNCA-mRNA and protein. Furthermore, the reduction in SNCA levels by the gRNA-dSaCas9-repressor system rescued disease-related cellular phenotypes including Ser129-phophorylated α-synuclein, neuronal viability, and mitochondrial dysfunction. We established a novel neuronal-type-specific SNCA-targeted epigenome therapy and provided in vitro proof of concept using human-based disease models. Our results support the therapeutic potential of our system for PD and DLB and provide the foundation for further preclinical studies in animal models toward investigational new drug (IND) enablement and clinical trials.

The efficient extraction, storage, and visualization of geometric and semantic information is a key foundation for the operation of the building information modeling (BIM) platform. This study aims to develop a lightweight BIM system and optimize the system’s performance according to the specific characteristics of steel structures. This study proposes several novel techniques for extracting and decoupling the geometric and semantic information of components from industry foundation class (IFC) files. A redundancy removal approach combining the principal content analysis (PCA) algorithm and the Hausdorff-based comparison algorithm is proposed to identify standardized steel components, and a lightweight visualization method on Web3D for redundant instances is also presented. A loading mechanism of the level of detail (LOD) model based on a mesh simplification algorithm is presented to optimize the display efficiency. The developed system is evaluated by three steel structural models. Using the redundancy removal approach, the number of instances is decreased by 96.46% in less than 30 s and over 30 FPS (frame per second) is kept when rendering. Using the LOD loading mechanism, 95.38% of vertices and 98.46% of patches are eliminated under 50 mm precision. The experiment results indicate that users can quickly load large BIM models and fetch sufficient information from the website.

In this paper, semideterministic multi-input multi-output (MIMO) channel modeling is proposed for a tunnel with two types of cross sections. To be more consistent with the MIMO propagation characteristics of the measured data, ray tracing (RT) is used to simulate the specular components (SCs) and a directed path channel modeling method based on directive scattering model (DSM) is used to simulate the diffuse components (DCs), which has an important contribution in MIMO channel capacity. The performance of the proposed model is compared in terms of delay domain, angle domain, and channel capacity. By analyzing the DSM and the propagation graph based on the Lambertian scattering model (LSM), it was demonstrated that the proposed method is more suitable in terms of comprehensive performance.

Abstract Background Breast cancer is a serious threat to female health, and its incidence varies with education level (EL). In the present study, the association between EL and the risk of developing female breast cancer was investigated. Methods From May 2006 to December 2007, 20,400 observation subjects in Kailuan Cohort received questionnaires and were subjected to clinical examinations for data collection on baseline population characteristics, height, weight, lifestyle and past disease history. Then, these participants were followed up with from the date of recruitment to December 31, 2019. Cox proportional risk regression models were used to analyse the association between EL and the risk of developing female breast cancer. Results The cumulative follow-up period of 20,129 observation subjects that meet the inclusion criteria of this study was 254,386.72 person-years, and the median follow-up time was 12.96 years. During the follow-up period, 279 cases of breast cancer were diagnosed. In comparison with the low EL group, the risk of developing breast cancer was significantly higher in the medium (hazard ratio [HR] (95% confidence interval [CI]) = 2.23 (1.12–4.64)] and high [HRs (95% CI) = 2.52 (1.12–5.70)] EL group. Conclusion An increased risk of breast cancer was associated with a higher EL, and some certain factors, such as alcohol use and hormone therapy, may play a mediating role.

For the problem of communication jamming effectiveness, an effective jamming coefficient was proposed as an evaluation metric based on the correlation between jamming and communication signals, and the impact of orthogonal receivers was analyzed.Specially, minimum shift keying (MSK) and several typical binary modulation signals were chosen as the target communication and jamming signals, respectively.Jamming effectiveness evaluation was performed for the above mentioned scenario by deriving its theoretical bit error rate (BER) formulas.Moreover, for coherent jamming scenario with MSK being the jamming signal, the impact of its phase difference, frequency difference and delay on the jamming effectiveness were also systematically analyzed.The analysis suggests that to achieve better jamming effectiveness, different jamming modulation scheme should be chosen according to the signal-to-noise (SNR) of the jamming communication signal.Simulation has also shown that there is a good match between the derived theoretical analysis and numerical simulation of the proposed method effectiveness, which has proven its accuracy and validity.

Multi-GNSS PPP partial ambiguity resolution (PAR) can improve the fixing success rate and shorten the time to first fix (TTFF). Ambiguity subset selection based on the bootstrapping success rate sorting criterion (BSSC) is widely used in PPP PAR due to its ease of computation and comprehensive evaluation of the global quality of ambiguity solutions. However, due to the influence of unmodeled errors, such as atmospheric residuals and gross errors, ambiguity parameter estimation will inevitably introduce bias. For ambiguity parameters with bias, their variance will converge incorrectly and will not accurately reflect the estimation accuracy. As a result, the selected ambiguity subset based on the BSSC becomes inaccurate, affecting the fixing success rate and TTFF. Therefore, we proposed an improved multi-GNSS PPP PAR method based on a two-step sorting criterion (TSSC). This method aims to address the influence of inaccurate variance of ambiguity parameters, particularly those with low observation quality, on the ambiguity subset selection based on the BSSC. The ambiguity subset satisfying the preset success rate threshold is selected to reduce the influence of unconverged ambiguity on the TSSC. In the first step of the sorting process, the observations whose elevation angle is below 30° or whose posterior residual falls into the IGG3 model reduction domain are clustered together. The posterior observation weight criterion (POWC) instead of the BSSC is adopted to sort ambiguities to overcome the false convergence of variance of ambiguity parameters. In the second step of the sorting process, the remaining ambiguities with reasonable variances are sorted based on the BSSC. Finally, the bottom ambiguity is removed one by one from the ambiguity subset sorted based on the two-step sorting criterion (TSSC) until the requirements of the ratio test for LAMBDA are met. The static data from 10 MGEX stations over a period of 30 days, along with urban kinematic data, were collected to validate the proposed method. Compared with the PAR based on the BSSC, the static experiments demonstrated a reduction of 8.7% and 16.8% in the TTFF and convergence time, respectively. Additionally, the positioning accuracy in the east, north, and up directions was improved by 20.1%, 17.1%, and 4.67%, respectively. Furthermore, the kinematic experiment revealed that the TTFF and convergence time decreased from 1.65 min and 10.5 min to 1.3 min and 1.8 min, respectively, with higher positioning accuracy.

The Dempster-Shafer(DS) evidence theory was applied to cooperative spectrum sensing and address the paradox of evidence in classical DS evidence theory, a new weighted distance measure based algorithm was proposed.Firstly, the evidences were extracted for each sensing user.Then, the weighted distance measure of extracted basic probability assignment data was adopted as the similarity between evidences of sensing users.Finally, the similarity of evidences was transformed into credibility, which was utilized as the weight to obtain the weighted average of basic probability assignment.In order to reduce the amount of data reported to the fusion center, the projection approximation method was employed to adjust the basic probability assignment.Both theoretical analysis and simulation results show that the proposed method can improve the detection performance of spectrum sensing while the paradox of evidence exists.Compared with traditional methods the cooperation overhead is reduced.

With the full operation of the global BeiDou navigation satellite system (BDS-3), positioning performance can be further enhanced by BDS-3 combined with the regional BeiDou navigation satellite system (BDS-2). However, due to satellite signals being out of lock and the limited visibility of satellites, the traditional multi-frequency BDS-2/3 precise point positioning (PPP) model is unable to maintain great positioning performance under urban environmental conditions. In this study, a mixed multi-frequency undifferenced and uncombined (UDUC) BDS-2/3 PPP model is presented to improve the positioning performance under urban environmental conditions by making full use of B1I, B1C, B2I, B2a, and B3I signals from all visible BDS satellites. In this model, BDS satellites with single-, dual-, triple- and quad-frequency observations all can participate in PPP. The static and kinematic experiments were carried out using the mixed multi-frequency UDUC BDS-2/3 PPP model to fully assess the positioning performance under urban environmental conditions with comparisons to the multi-frequency model. The static experiments indicated that the mixed multi-frequency UDUC BDS-2/3 PPP could continuously achieve decimeter-level positioning accuracy at a cut-off elevation angle of 40°, but part of the BDS-3 PPP would lose resolution due to limited visible satellites. Furthermore, the initial kinematic vehicle experiment showed that mixed multi-frequency UDUC BDS-2/3 PPP had better satellite geometry and more observation redundancy than the traditional multi-frequency model. Compared with the traditional multi-frequency BDS-2/3 model, the positioning accuracy of the mixed multi-frequency model was improved by 51.6, 35.5, and 39.1%, respectively, in east, north, and up directions. The convergence time was shortened by 40%.

Component doping is the fundamental topic for modulating the properties of semiconductor materials. The introduction of doping ions into lead halide perovskites (LHPs) can not only maintain the excellent photoelectric properties but also enhance the stability of LHPs in open air and thermal environments. However, due to the "self-purification" effect in crystallography, there is an inherent trend to pop doping ions out of LHPs lattice. In this work, it is confirmed that in Mn2+ doped LHPs nanocrystals (NCs) the discharge of Mn2+ will be accelerated at higher temperatures. It is also proved that even at room temperature, the dopants in LHPs NCs will also actively "migrate", resulting in declined optical performance. Therefore, for cation alloying/doping LHPs NCs, the migration of doping ions in the material should be considered in addition to the intrinsic halide migration characteristics. This work will provide a benign reference for application of doped LHPs NCs. [ABSTRACT FROM AUTHOR]

In the new era, there is an urgent need to further promote pairing assistance to Tibet, promote the simultaneous construction of a strong agriculture in China, and compose a Chinese-style modernization. Southern Tibet, located in the southeastern part of the Tibet Autonomous Region, includes Shannan City and Nyingchi City, is a region assisted by four provincial partners including Hubei Province. This paper introduces the agricultural environment in southern Tibet, studies its agricultural characteristics, and analyzes the main issues of its pairing assistance. Taking forging the strong consciousness of the Chinese national community as the main line, the paper explores strategies for promoting agricultural high-quality development in southern Tibet through pairing assistance to Tibet from the perspective of agricultural power, and proposes some strategies, such as inheriting agricultural cultural heritage, promoting the upgrading of modern seed industry, enhancing the characteristic advantages of highland barley (naked barley) and animal husbandry industries, and developing edible fungi and cold water fish industries. [ABSTRACT FROM AUTHOR]

Establishing the Greater Food Approach and promoting the Yangtze River Economic Belt's national major regional development strategy can better support and serve the agricultural power and Chinese-style modernization. This paper introduces the characteristics of fruit industry in 16 autonomous prefectures and 47 autonomous counties under the jurisdiction of the Yangtze River Economic Belt. It studies the intellectual property resources of brand marks from the aspects of geographical indications, collective trademarks, certification trademarks, well-known trademarks in China and national design patents, and analyzes the main problems of brand and high-quality development of fruit industry in these ethnic autonomous areas. Finally, it puts forward some strategies, such as improving the protection of intellectual property rights of geographical indications, using intellectual property rights of brand signs, building modern seed industry upgrading project, drawing lessons from the experience of thousand villages demonstration project, ensuring that large-scale poverty does not occur, and building a diversified food supply system. [ABSTRACT FROM AUTHOR]

Accelerating the construction of agricultural power, further promoting the high-quality development of the Yangtze River Economic Belt, and better supporting and serving Chinese-style modernization are the key issues at present. This paper first introduces the Yangtze River Economic Belt and its ethnic areas, and studies the characteristics of the grain and oil industry in the ethnic autonomous areas of the economic belt, as well as the current situation of various types of intellectual property resources, such as industrial cultural heritage, scientific and technological innovation, and brand marking intellectual property. Besides, it analyzes the main problems in the high-quality development of grain and oil in the Yangtze River Economic Belt ethnic areas. Finally, it comes up with recommendations, including protecting the intellectual property rights of cultural heritage in the field of grain and oil, leading the inheritance and development of excellent traditional Chinese culture, use scientific and technological innovation intellectual property rights to promote the innovation-driven development strategy of the grain and oil industry, and providing counterpart assistance to ethnic autonomous areas in the Yangtze River Economic Belt to further promote the high-quality development of the Yangtze River Economic Belt. [ABSTRACT FROM AUTHOR]

Abstract The cell range expansion (CRE) is encouraged to be applied in the heterogeneous cellular networks (HCNs), to enhance the capacity by offloading macro users to small cells. However, the enhanced inter-cell interference coordination (eICIC) techniques are supposed to be used for mitigating the strong cross-tier interference suffered by the offloaded users and small cell edge users. To address this, a novel soft frequency reuse (SFR) scheme is adopted in this paper. We analyze multichannel downlink scenarios for the SFR scheme using the tools of stochastic geometry. In consideration of the random resource allocation and practical cell load model, the analytical results of coverage probability and average user rate are derived and validated through Monte Carlo methods. Furthermore, our results can reduce to simple closed-form under reasonable special case for modern urban cellular networks. The main evaluation of the performance in terms of average user rate is presented, and the optimal combination of association bias and parameters of the SFR scheme is also investigated. Numerical results show that the SFR scheme outperforms the frequency resource partitioning (FRP) scheme in any load condition. Moreover, the CRE with SFR scheme can improve the average user rate significantly.

[This corrects the article DOI: 10.1371/journal.ppat.1007253.].

Only by improving the production capacity of domestic herbal edible oil can China ensure the safety of the supply chain of the important industrial chain of vegetable edible oil in China and practice the big food concept. In addition to rice, maize, and soybean for using as grain and oil, there are eight kinds of herbaceous edible oil crops in Hubei Province, including rape, peanut, sesame, sunflower, perilla ( perilla seed), cotton, linen and tiger nut ( Cyperus esculentus). This paper studies the main industries of herbaceous edible oil crops and their intellectual property resources in Hubei Province, and analyzes the main problems of its inheritance, innovation and high-quality development under the strategy of strengthening the country with intellectual property. Finally, it proposes the countermeasures of carrying forward and inheriting traditional knowledge and traditional culture, maintaining the biodiversity of crops, strengthening the creation of new plant varieties and breeding patents, and opening up the whole chain of intellectual property rights. [ABSTRACT FROM AUTHOR]

Only by developing woody edible oilseeds industry can we ensure the safety of the important industrial chain and supply chain of vegetable edible oil in China. There are 13 kinds of woody edible oil plants in Hubei, including Camellia oleifera Abel (oil tea), Juglans regia L. (walnut), Olea europaea L. (olive) and Paconia suffruticosa (oil peony). This paper studies the main industries of woody edible oilseeds in Hubei Province and their intellectual property resources, and analyzes the main problems in their intellectual property protection, inherit- ance, innovation and development. Finally, it proposes some strategies, including carrying forward the traditional knowledge related to woody edible oilseeds, innovating the "agricultural chip", creating key counties of national woody edible oil seeds, and developing industrial clusters with national advantages and characteristics. [ABSTRACT FROM AUTHOR]