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Abstract As human activities continue to expand, wildlife persistence faces escalating threats from roads. In Wolong area of Giant Panda National Park, the local giant pandas (Ailuropoda melanoleuca) are divided into two population groups along the National Highway G350 (NHG). Therefore, selecting suitable areas to help those giant pandas communicate across the NHG is necessary. In this research, we evaluated the presence of human activities and simulated their absence to analyze how they affect the giant panda's habitat in Wolong. Subsequently, based on the kernel density estimation (KDE) for giant pandas and the main human distribution locations, we selected suitable areas for the population link between the two road sections on the NHG. We simulated the absence of human activities on the two road sections to compare changes in the habitat suitability index (HSI) and connectivity value (CV) relative to their presence. We aimed to carefully select the area for future giant panda corridor plans and simulate whether eliminating human activities will significantly improve the HSI and CV of the area. Our results show that: (1) Human activities presence has led to subtle changes in the landscape pattern of suitable habitats and a decrease in Wolong by 78.76 km2 compared to their absence. (2) Human activities presence significantly reduced HSI and CV in the 1000 m buffer along the NHG compared to their absence. (3) The HSI and CV of the 1000 m buffer in the simulated absence of human activities for the two road sections were significantly higher than their presence. This research identified the optimal road section for crossing the NHG to link giant panda population groups and habitats in Wolong. These insights are significant for formulating conservation decisions and corridor plans and for promoting wildlife conservation in reserves amid high levels of human activity.

Abstract Background ARHGAP10 is a tumor‐suppressor gene related to ovarian cancer (OC) progression; however, its specific mechanism is unclear. Aims To investigate the effect of ARHGAP10 on OC cell migration, invasion, and glycolysis. Methods and Results Quantitative real‐time PCR (qRT‐PCR) quantified mRNA and protein expressions of AKT, p‐AKT, HK2, and SMAD4 were tested by Western blot. EdU, Wound healing, and Transwell assay were utilized to evaluate OC cell proliferation, migration, and invasion. We used a Seahorse XF24 Extracellular Flux Analyzer to monitor cellular oxygen consumption rates (OCR) and extracellular acidification rates (ECAR). Chromatin immunoprecipitation (ChIP) was used to analyze the transcriptional regulation of ARHGAP10 by SMAD4. ARHGAP10 expression in OC tissues was detected by immunohistochemistry. Our results showed that ARHGAP10 expression was negatively related to lactate levels in human OC tissues. ARHGAP10 overexpression can inhibit the migration, proliferation, and invasion of OC cells, and this function can be blocked by 2‐Deoxy‐D‐glucose. Moreover, we found that ARHGAP10 expression can be rescued with the AKT inhibitor LY294002. Conclusions This study revealed that the antitumor effects of ARHGAP10 in vivo and in vitro possibly suppress oncogenic glycolysis through the PI3K/AKT/HK2‐regulated glycolysis metabolism pathway.

Abstract Background Imatinib is the standard first‐line treatment for advanced gastrointestinal stromal tumors (GISTs); however, most patients eventually develop imatinib resistance, leading to considerable clinical challenges. Few direct comparisons have been made between different post‐first‐line therapies on clinical efficacy in advanced GIST following imatinib failure. Methods Databases including PubMed, Embase, Scopus, Google Scholars, and Cochrane Library from inception to February 2023 were retrieved for randomized controlled trials evaluating the clinical efficacy of different post‐first‐line agents for advanced GIST following imatinib failure. Network and conventional meta‐analysis were carried out using Stata/MP 16.0. Results Ripretinib showed significant improvement in progression‐free survival (PFS) rates from the 2nd to the 12th month compared to placebo, while there was virtually no evidence that the rest active agents had a significant benefit at the 12th month. Masitinib, ripretinib, sunitinib, regorafenib, and pimitespib exhibited significantly longer median PFS than placebo, and pairwise comparisons indicated there were no significant differences among masitinib, ripretinib, and sunitinib. These post‐first‐line agents decreased the risk of disease progression or death by 65% (HR = 0.35, 95% CI: 0.26–0.47) compared to placebo. Ripretinib and sunitinib came into effect earlier and exhibited more consistent overall survival (OS) rate improvements than masitinib and pimitespib, while pairwise comparisons revealed no significant differences in these four active agents concerning the improvement in OS rate. These post‐first‐line agents decreased the risk of death by 39% (HR = 0.61, 95% CI: 0.44–0.83) over placebo for advanced GIST following imatinib failure. Conclusion The active agents in our analysis as post‐first‐line therapies are able to provide superior clinical efficacy, with improved PFS rate and OS rate at certain time points, as well as absolute values of PFS and OS for advanced GIST. Ripretinib might be the optimal recommendation as a post‐first‐line treatment for advanced GIST following imatinib failure.

Abstract Background Exercise is an affordable and practical strategy to alleviate several detrimental outcomes from the aging process, including sarcopenia. The elucidation of molecular mechanisms to alleviate sarcopenia is one of the most important steps towards understanding human aging. Although microRNAs (miRNAs) regulate muscle growth, regeneration and aging, the potential role of exercise‐mediated miRNAs during the prevention and rehabilitation of skeletal muscle atrophy upon exercise interventions remains unclear. Methods A miRNA profile by miRNA sequencing for gastrocnemius muscle of a 24‐month‐old aged male rat model mimicking the naturally aging process was established through screening the differentially expressed miRNAs (DEMs) for alleviating aging‐induced skeletal muscle atrophy upon optimal exercise intervention. The screened miRNAs and hub genes, as well as biomarkers with the most significantly enriched pathways, were validated by quantitative real‐time polymerase chain reaction and western blotting. Results The sarcopenia index (SI) value and cross‐sectional area (CSA) of rats from the old control (OC) group significantly decreased when compared with the youth control (YC) group (P 1) between the YC group and the OC group. Compared with the OC group, 7, 2 and 11 miRNAs were differentially expressed in the OE, OR and OM groups after exercise interventions, respectively. Meanwhile, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that the identified DEMs were primarily related to apoptosis, autophagy and the NF‐κB/MuRF1 signalling pathways (P

Abstract The consensus mechanism is a key technology to achieve state consistency among distributed nodes and it determines the consensus efficiency and stability of the blockchain system. If the consensus efficiency and stability are improved, that can promote the development of the entire society. Therefore, it is necessary to improve the consensus efficiency and stability of the blockchain system. However, there are many disadvantages in the existing consensus mechanism, such as high communication complexity, low throughput, and poor scalability. For solving these disadvantages, a blockchain consensus mechanism Score‐Based Byzantine Fault Tolerance (SBBFT) is proposed. First, the score of nodes are obtained by Analytical Hierarchy Process (AHP) and SBBFT uses the score of the node to choose a node to be the primary node and acknowledgment node. Second, SBBFT selects c acknowledgment nodes to be an acknowledgment node subset. This subset can change the communication of nodes from all‐to‐all to all‐to‐c. Moreover, the view change of acknowledgment node subset can make the system resistant to attacks from more malicious nodes. According to the experiment, 900,000 transactions from Ethereum, the result demonstrates SBBFT can significantly reduce the communication complexity, improve the consensus efficiency and stability of the system.

Abstract Aims Elderly patients with heart failure (HF) are associated with frequent all‐cause readmission or death. The present study sought to develop an accurate and easy‐to‐use model to predict all‐cause readmission or death risk in Chinese elderly patients with HF. Methods and results This was a prospective cohort study in patients with HF aged 65 or older. Demographic, co‐morbidity, laboratory, and medication data were collected. A Cox regression model was used to identify factors for the prediction of readmission or death at 30 days and 1 year. A nomogram was developed with bootstrap validation. Of the included 854 patients, the cumulative all‐cause readmission and mortality rates were 10.5% and 11.6% at 30 days and 34.9% and 19.7% at 1 year, respectively. The independent risk factors associated with both 30 day and 1 year readmission or death were older age, stroke, diastolic blood pressure 400 pg/mL (all P

Response of pore-water pressure has crucial effect on the engineering geological performance of permafrost ground. However, there is a dearth of literature on the measurement of pore-water pressure in frozen soils due to challenges with regard to technical and operational method. To validate the generation of pore-water pressure and to reveal its variation property in frozen soils at subfreezing temperatures close to 0°C, a miniature pressure transducer was utilized to conduct a number of confined compression tests. Double-wall structure avoided damage to the transducer during frozen soil sampling. The transducer at sample bottom perceived a pressure fluctuation as varying air pressure imposed on sample surface, proving the connectivity among the pores in frozen soils with a hysteretic effect on pressure transmission. Pore-water pressure experienced a progressive increase followed by a slow dissipation under invariable load and temperature conditions when water drainage was permitted, while a monotonic increase in pressure was observed for an undrained sample. With decreasing temperature, a smaller peak and a more dilatory dissipation were displayed. When the sample was exposed to a stepwise warming process, a similar performance for the pressure was obtained with abrupt rise at the turning point of temperature.

Characterized by low bearing capacity and high compressibility, warm and ice-rich frozen soil is a kind of problematic soil, which makes the original frozen ground formed by of that unreliable to meet the stability requirements of engineering infrastructures and foundations in permafrost regions. With the design and construction of major projects along the Qinghai-Tibet Engineering Corridor (QTEC), such as expressway and airport runway, it is a great challenge to favor the stability of overlying structures by formulating the proper engineering design principles and developing the valid engineering supporting techniques. The investigations carried out in recent years indicated that warm and ice-rich permafrost foundations were widespread, climate warming was significant, and the stability of existing engineering structures was poor, along the QTEC. When the warm and ice-rich frozen ground is used as the foundation soil, the implementation of ground improvement is an alternative measure to enhance the bearing capacity of foundation soil and eliminate the settlement of structures during operation, in order to guarantee the long-term stability of the structures. Based on the key factors determining the physicomechanical properties of frozen soil, an innovative idea of stabilizing the warm and ice-rich frozen soil based on chemical stabilization is proposed in this study, and then, an in situ ground improvement technique is introduced. This study intends to explore the feasibility of ground improvement in warm and ice-rich permafrost regions along the QTEC based on in situ chemical stabilization and provide the technical support and scientific reference to prevent and mitigate the hazards in the construction of major projects in the future.

Abstract Supramolecular self‐assemblies of dendritic peptides with well‐organized nanostructures have great potential as multifunctional biomaterials, yet the complex self‐assembly mechanism hampers their wide exploration. Herein, a self‐stabilized supramolecular assembly (SSA) constructed from a PEGylated dendritic peptide conjugate (PEG‐dendritic peptide‐pyropheophorbide a, PDPP), for augmenting tumor retention and therapy, is reported. The supramolecular self‐assembly process of PDPP is concentration‐dependent with multiple morphologies. By tailoring the concentration of PDPP, the supramolecular self‐assembly is driven by noncovalent interactions to form a variety of SSAs (unimolecular micelles, oligomeric aggregates, and multi‐aggregates) with different sizes from nanometer to micrometer. SSAs at 100 nm with a spherical shape possess extremely high stability to prolong blood circulation about 4.8‐fold higher than pyropheophorbide a (Ppa), and enhance tumor retention about eight‐fold higher than Ppa on day 5 after injection, which leads to greatly boosting the in vivo photodynamic therapeutic efficiency. RNA‐seq demonstrates that these effects of SSAs are related to the inhibition of MET‐PI3K‐Akt pathway. Overall, the supramolecular self‐assembly mechanism for the synthetic PEGylated dendritic peptide conjugate sheds new light on the development of supramolecular assemblies for tumor therapy.

This paper investigates the pricing of discretely sampled variance swaps under a Markov regime-switching jump-diffusion model. The jump diffusion, as well as other parameters of the underlying stock’s dynamics, is modulated by a Markov chain representing different states of the market. A semi-closed-form pricing formula is derived by applying the generalized Fourier transform method. The counterpart pricing formula for a variance swap with continuous sampling times is also derived and compared with the discrete price to show the improvement of accuracy in our solution. Moreover, a semi-Monte-Carlo simulation is also presented in comparison with the two semi-closed-form pricing formulas. Finally, the effect of incorporating jump and regime switching on the strike price is investigated via numerical analysis.

Based on the background of the reconstruction project from Changqing Chenzhuang-Pingyin section of G220 east-deep line in China, a special tunnel structure and construction plan was carried out according to the construction measures of the shallow-buried small spacing tunnel passing underneath cultural relic buildings, and a comprehensive deformation control scheme of “CRD construction method single-arm excavation + surface grouting prereinforcement + advanced large pipe shed presupport” was put forward. The results of numerical simulation and on-site construction monitoring showed that the overall deformation of aqueduct foundation generally increases first, then decreases and increases again, and finally tends to be stable. The effects of surface grouting prereinforcement and advance large pipe shed presupport are obvious. The comprehensive deformation control scheme can ensure the safety of the existing construction and meet the safety prevention and control requirements.

Abstract Herein, two water‐soluble PROXYL‐based magnetic resonance imaging (MRI) macromolecular organic contrast agents (mORCAs) are designed and synthesized: linear and cross‐linked PCE‐mPEG‐Ppa‐PROXYL. They are prepared by conjugating linear and cross‐linked poly(carboxylate ester) (PCE) with poly(ethylene glycol) (mPEG2000)‐modified nitroxides (PROXYL), respectively. Both mORCAs form self‐assembled aggregates in an aqueous phase and PROXYL is protected inside a hydrophobic core to achieve great resistance to reduction in the physiological environment, and they have low toxicity. Since cross‐linked PCE‐mPEG‐Ppa‐PROXYL possess a branched architecture, its self‐assembled aggregate is more stable and compact with a greater particle size. Cross‐linked PCE‐mPEG‐Ppa‐PROXYL outperform the linear one in the following aspects: 1) its longitudinal relaxivity (r1 = 0.79 mm−1 s−1) is higher than that of the linear one (r1 = 0.64 mm−1 s−1) and both excel the best mORCA reported so far (r1 = 0.42 mm−1 s−1); 2) its blood retention time (≈48 h) is longer than that of its linear counterpart (≈10 h); 3) cross‐linked PCE‐mPEG‐Ppa‐PROXYL provided better MR imaging contrast resolution in normal organs (liver and kidney) and tumor of mice than the linear one. Overall, cross‐linked PCE‐mPEG‐Ppa‐PROXYL may have great potential to be a novel metal‐free macromolecular contrast agent for MR imaging.

Abstract A stimuli‐responsive polymeric prodrug‐based nanotheranostic system with imaging agents (cyanine5.5 and gadolinium‐chelates) and a therapeutic agent paclitaxel (PTX) is prepared via polymerization and conjugating chemistry. The branched polymeric PTX‐Gd‐based nanoparticles (BP‐PTX‐Gd NPs) demonstrate excellent biocompatibility, and high stability under physiological conditions, but they stimuli‐responsively degrade and release PTX rapidly in a tumor microenvironment. The in vitro behavior of NPs labeled with fluorescent dyes is effectively monitored, and the NPs display high cytotoxicity to 4T1 cells similar to free PTX by impairing the function of microtubules, downregulating anti‐apoptotic protein Bcl‐2, and upregulating the expression of Bax, cleaved caspase‐3, cleaved caspase‐9, cleaved‐PARP, and p53 proteins. Great improvement in magnetic resonance imaging (MRI) is demonstrated by these NPs, and MRI accurately maps the temporal change profile of the tumor volume after injection of NPs and the tumor treatment process is also closely correlated with the T1 values measured from MRI, demonstrating the capability of providing real‐time feedback to the chemotherapeutic treatment effectiveness. The imaging‐guided chemotherapy to the 4T1 tumor in the mice model achieves an excellent anti‐tumor effect. This stimuli‐responsive polymeric nano‐agent opens a new door for efficient breast cancer treatment under the guidance of fluorescence/MRI.

In a bus line with high passenger demand, the stop-skipping operation can benefit both users and operators as well as improve the service level of bus line, but it usually cannot be effectively adopted by operators because of the unordered operation of buses and the discomfort of waiting passenger at stops. Therefore, the stop-skipping operation requires higher reliability for stop serving. This paper proposes a reliable stop-skipping service design with holding strategy by taking into account bus capacity constraints. Under a stop-skipping service, the holding strategy is used to balance the interval of stop serving rather than the headway of buses. Meanwhile, to reflect the actual boarding process of waiting passengers, the number of left-over passengers and the waiting time are calculated during serving time and holding time, respectively. The objective function is to minimize the total costs of bus operation system. Besides, a Genetic Algorithm combined with Monte Carlo Simulation method is defined and implemented to solve the reliability optimization model. Finally, a numerical example based on a bus route in Changchun city is carried out to test the reliability optimization model. Results showed that the reliability optimization strategy can improve the stability of stop service and then save cost of passengers’ travel time.

Indoxacarb is a broad-spectrum insecticide and widely used in agriculture. The dissipations and residues of indoxacarb were researched at three different field sites in Beijing, Hunan, and Zhejiang provinces in China. Analytical methods for determining the residue of indoxacarb in paddy water, paddy soil, rice straw, rice hull, and brown rice were described. Indoxacarb residues were extracted from samples, cleaned up by solid phase extraction, and determined by high-performance liquid chromatography coupled with tandem mass spectrometry in the selected ion monitoring mode. The recoveries in paddy water, paddy soil, rice straw, rice hull, and brown rice matrices at three spiking levels ranged from 79.7% to 98.3%, respectively. The field and environmental conditions would affect the dissipations and residues of indoxacarb. The time to dissipate 50% of indoxacarb in paddy water, paddy soil, and rice straw was less than 9 days. The terminal residues obtained from Beijing at preharvest interval of 14 and 21 days were higher than the maximum limit of European Union. Therefore, a dosage of 24 g a. i. ha−1 at 28 days preharvest interval with 3 spraying times was recommended. Such accumulation of measured data is necessary to provide guidance for the proper and safe use of this pesticide.

The classification of natural scene images is multi‐instance multi‐label (MIML) for many labels that exist in a natural scene image. The traditional method of solving MIML is to degenerate it into single‐instance single‐label learning (SISL). However, the precision of the method could decrease due to information loss during the degeneration process. How to reasonably solve the MIML problem is key to obtaining high accuracy in this research area. An MIML algorithm based on instances via combining sparse coding with a deep neural network is proposed. First, an instance‐based sparse representation with dictionary learning is adopted. Second, an MIML description model based on a deep network is proposed, which can realise parameter self‐learning in combination with sparse representations. Third, the residuals of the sparse representation are introduced to the deep neural network. The results of the experiments show that the method outperforms a number of state‐of‐the‐art approaches.

Inflammatory bowel disease (IBD) is a complicated disease involving multiple pathogenic factors. The complex relationships between long-chain fatty acids (LCFAs) and the morbidity of IBD drive numerous studies to unravel the underlying mechanisms. A better understanding of the role of LCFAs in IBD will substitute or boost the current IBD therapies, thereby obtaining mucosal healing. In this review, we focused on the roles of LCFAs on the important links of inflammatory regulation in IBD, including in the pathogen recognition phase and in the inflammatory resolving phase, and the effects of LCFAs on immune cells in IBD.

Parasite-associated colitis is quite rare in clinical practice of Ulcerative Colitis (UC). Here we reported an intestinal giardiasis case that has been diagnosed with UC. Further examination of stool revealed cysts of Giardia. This case completely responded to Albendazole. Giardiasis should be included for the differential diagnosis of UC.

In a traditional transit system, passenger arrival time and bus running time are typically random and uncoordinated. This randomness gives the appearance of unbalanced passenger demand and unreliable transit services. Therefore, this paper proposes a real-time control method for bus routes. In our method, buses skip some stations and turn back at appropriate stations, in order to balance passenger demand along the bus route and improve the overall transit service. Our real-time control method considers the typical changes in passenger demand and the stochastic travel time of buses. In this paper, the number of controlled vehicles at any given time is determined, and the bus holding time at the turn-back station is adopted. When implemented correctly, the optimal scheme indicates which stations should be skipped, where it is suitable for buses to turn back, and how long the holding time should be at turn-back stations, which in turn will minimize the total cost of a transit system. This paper formulates such an integrated strategy, presents the solution method of the formulation, and proves the validity of the real-time control method.

The purpose of this paper is to show a novel fault-tolerant tracking control (FTC) strategy with robust fault estimation and compensating for simultaneous actuator sensor faults. Based on the framework of fault-tolerant control, developing an FTC design method for wind turbines is a challenge and, thus, they can tolerate simultaneous pitch actuator and pitch sensor faults having bounded first time derivatives. The paper’s key contribution is proposing a descriptor sliding mode method, in which for establishing a novel augmented descriptor system, with which we can estimate the state of system and reconstruct fault by designing descriptor sliding mode observer, the paper introduces an auxiliary descriptor state vector composed by a system state vector, actuator fault vector, and sensor fault vector. By the optimized method of LMI, the conditions for stability that estimated error dynamics are set up to promote the determination of the parameters designed. With this estimation, and designing a fault-tolerant controller, the system’s stability can be maintained. The effectiveness of the design strategy is verified by implementing the controller in the National Renewable Energy Laboratory’s 5-MW nonlinear, high-fidelity wind turbine model (FAST) and simulating it in MATLAB/Simulink.

This paper formulates a dynamic approach for real-time bus control in uncertain demand. This dynamic approach aims to save the total cost for passengers and operators, while improving transit service reliability. An unfixed rolling horizon was implemented to choose the best dynamic approach. Real-time control predicts two discrete variables (arrival time and bus position) and determines the space-time point of buses. Furthermore, controlled actions include stop skipping and bus holding. The holding time starts when a bus serves a station and depends on previous intervals of passenger boarding and alighting at the station. The stop skipping action allows a bus to skip not only stations with a short-turning exception, but also stations with low demand for boarding that have been alighted in the short-turning segment. Stop skipping and bus holding actions for short-turning service both decrease the travel time of served passengers and the running time of buses, thus improving transit service reliability. A genetic algorithm was applied to solve the problem and the validity of the proposed dynamic approach was tested with four different scenarios. The result of these tests shows that a dynamic short-term bus control can significantly reduce total cost and improve transit service reliability.

Patients with inflammatory bowel disease (IBD) are at an increased risk of developing colorectal cancer (CRC). The risk factors of CRC in IBD patients include long disease duration, extensive colitis, severe histological inflammation, and coexistence with primary sclerosing cholangitis (PSC). Several molecular pathways that contribute to sporadic CRC are also involved in the pathogenesis of colitis-associated CRC. It is well established that long-standing chronic inflammation is a key predisposing factor of CRC in IBD. Proinflammatory pathways, including nuclear factor kappa B (NF-κB), IL-6/STAT3, cyclooxygenase-2 (COX-2)/PGE2, and IL-23/Th17, promote tumorigenesis by inducing the production of inflammatory mediators, upregulating the expression of antiapoptotic genes, and stimulating cell proliferation as well as angiogenesis. Better understanding of the underlying mechanisms may provide some promising targets for prevention and therapy. This review aims to elucidate the role of these signaling pathways in the pathogenesis of colitis-associated CRC using evidence-based approaches.