Search Results (25)

Upper tract urothelial carcinoma (UTUC) is a rare and aggressive malignancy, accounting for only 5–10% of all urothelial carcinomas (UCs). Lung, bone, liver, and distant lymph nodes are common sites of metastasis, while gastrointestinal metastasis is extremely rare. We present a case of a 63-year-old female who developed a descending colon lesion 19 months after left radical nephroureterectomy for high-grade ureteral UC. The diagnosis was established by computed tomography (CT), magnetic resonance imaging (MRI), colonoscopy, and biopsy, which excluded primary colorectal malignancy. First-line therapy consisted of six 21-day cycles of gemcitabine plus cisplatin, followed by two cycles of tislelizumab maintenance immunotherapy. Restaging with contrast-enhanced CT and positron emission tomography/computed tomography (PET/CT) demonstrated disease progression. Despite switching to second-line nab-paclitaxel, the patient rapidly deteriorated from tumor cachexia and ultimately succumbed to septic shock secondary to severe pulmonary infection. This represents the first reported case of descending colon metastasis from primary ureteral UC. It highlights the colon as a potential metastatic site where biopsy is essential for definitive diagnosis. Notably, although the patient initially responded to platinum-based therapy, the subsequent rapid progression underscores the need for vigilant monitoring and timely adjustment of therapeutic strategies in managing such high-risk presentations. Full article

To compare the respiratory lesions and nervous system damage in cotton rats and BALB/c mice following respiratory syncytial virus (RSV) infection, and to evaluate their suitability as models for RSV-related respiratory and nervous system diseases, cotton rats and BALB/c mice were infected with RSV via intranasal instillation, monitored daily for weight and temperature. At 3, 5, and 7 days post-infection (dpi), viral loads in the nasal turbinates, lungs, and brain tissues were quantified. Pathological changes and neuroinflammatory responses in the lungs and brain were assessed using hematoxylin and eosin (H&E) staining, Nissl staining, immunofluorescence, and Western blotting analysis, while the mRNA expression levels of inflammatory factors were specifically analyzed at 5 dpi. The results showed that viral loads in the nasal turbinates and lungs of cotton rats were significantly higher than those in BALB/c mice, accompanied by more extensive pulmonary inflammatory factor gene upregulation at 5 dpi and more pronounced lung histopathological alterations. In contrast, RSV RNA and antigens were detected in the brain tissues of BALB/c mice, at levels markedly lower than those in respiratory tissues, along with viral antigens primarily localized to the choroid plexus epithelium. No significant pathological or neuroinflammatory changes were observed in the brains of cotton rats at any examined time point. In conclusion, cotton rats provide advantages for modeling RSV-associated respiratory tract infection and pulmonary pathology, whereas under the experimental conditions of this study, BALB/c mice may be more appropriate for investigating RSV-associated CNS inflammatory responses, although the clinical relevance of these findings remains to be further validated. Full article

Background: Colorectal cancer (CRC) is a leading cause of cancer death, and the incidence and mortality rates among young adults are rising. Although a subset of CRC cases presents with a family history, suggesting a hereditary component, the specific genetic underpinnings remain incompletely understood, particularly in early-onset CRC (EOCRC). This study aimed to discover novel risk genes for EOCRC using exome sequencing and gene-based rare variant burden testing. Methods: Our cohort consisted of 212 European-ancestry cases (174 diagnosed with CRC and 38 with significant polyps) from the South Australian Young Onset Colorectal Polyp and Cancer Study (SAYO) and 31,699 unaffected controls from the Simons Foundation Powering Autism Research for Knowledge (SPARK) cohort. After filtering for ancestry, relatedness, variant quality, and population allele frequency, we performed gene-set and individual-gene burden tests using predicted deleterious missense and loss-of-function variants. Statistical significance was assessed using permutation-corrected binomial testing. An independent validation was conducted in the UK Biobank. Results: Loss-of-function variants in known CRC tumor suppressor genes were significantly enriched in SAYO cases. Gene-level analyses identified MEIKIN as a novel EOCRC susceptibility candidate (p value = 1.0 × 10⁻⁷), with supporting enrichment of deleterious missense and loss-of-function variants in distal colon cancer cases from the UK Biobank. Additional genes (STK25, PGBD4, DIRAS3, ATG3, RPS6KA4, and DDX42) demonstrated borderline significance, implicating pathways related to kinetochore assembly, autophagy regulation, and immune signaling. Both predicted gain-of-function and loss-of-function variants contributed to the EOCRC risk, supporting heterogeneous mechanisms of CRC pathogenesis. Conclusions: This study identified novel candidate risk genes for EOCRC, underscoring the role of rare variants and expanding our understanding of the genetic architecture of CRC. Future studies should include functional validation and replication studies on other ancestries to confirm and extend these results. Full article

With the increasing integration of variable renewable energy into power systems, the frequency regulation capability of hydroelectric units has become crucial for ensuring grid stability. In response to grid disturbances, where Primary Frequency Regulation (PFR) and Automatic Generation Control (AGC) are activated sequentially in actual operation, this paper employs parameter characteristic analysis to systematically investigate the influence of several factors—including turbine operating head, PWM parameters, and governor parameters—on the active power regulation process of hydroelectric units. The study first compares the response characteristics under different heads and PWM/pulse parameters within the AGC framework. It then examines the effects of pulse duration limits and integral adjustments on guide vane movement and correction efficiency. Finally, under the PFR framework, the impacts of head, steady-state slip coefficient, and integral gain on the amplitude and speed of frequency response are analyzed. Simulation results demonstrate that as the set value of Tkmax increases, the operating range of the guide vane opening within the pulse cycle expands, and the time required for power correction is significantly reduced. Specifically, when Tkmax is increased from 0.2 to 0.55, the regulation time is shortened by 44%. These findings offer theoretical guidance and practical insights for parameter optimization and operational scheduling of hydropower units. Full article

An asymptotic stability velocity tracking controller is designed to enable the autonomous maneuvering flight of unmanned helicopters. Firstly, taking the UH-60A without pilots as the research object, a high-efficient rotor aerodynamic modeling is developed, which incorporates a free-wake vortex method with the flap response of blades. The consummate flight dynamic model is complemented by wind tunnel-validated fuselage/tail rotor load regressions. Secondly, a linear state–space equation is derived via the small perturbation linearization method based on the flight dynamic model within the body coordinate system. A decoupled model is formulated based on the linear state–space equation by employing the implicit model approach. Subsequently, a system of ordinary differential equations is constructed, which is related to the deviation between actual velocity and its expected value, along with higher-order derivatives of this discrepancy. The I&I (immersion and invariance) theory is then employed to facilitate the design of a non-cascade control loop. Finally, the response of desired velocity in longitudinal channel is simulated with step signal to compare the control effect with a PID (proportional–integral–derivative) controller. By adjusting the coefficients, the response progress of the PID controller is similar to the effect of adaptive controller with I&I theory. However, there is no obvious overshoot in the process with I&I adaptive controller, and the average response amplitude accounts for 16.69% of the random white noise, which is 7.38% of the oscillation level under the PID controller. The parameter tuning complexity when employing I&I theory is significantly lower than that of the PID controller, which is evaluated by mathematical derivations and simulations. Meanwhile, the sidestep and pirouette maneuvers are simulated and analyzed to examine the controller in accordance with the performance criteria outlined in the ADS-33E-REF standards. The simulation results demonstrate that the speed expectation-oriented asymptotic stability control can achieve a fast response. Both sidestep and pirouette maneuvers can satisfy the desired performance requirements stipulated by ADS-33E-REF. Full article

The control stability and accuracy of quad tiltrotor UAVs is improved when encountering external disturbances during automatic flight by an active disturbance rejection control (ADRC) parameter self-tuning control strategy based on a radial basis function (RBF) neural network. Firstly, a nonlinear flight dynamics model of the quad tiltrotor UAV is established based on the approach of component-based mechanistic modeling. Secondly, the effects of internal uncertainties and external disturbances on the model are eliminated, whilst the online adaptive parameter tuning problem for the nonlinear active disturbance rejection controller is addressed. The superior nonlinear function approximation capability of the RBF neural network is then utilized by taking both the control inputs computed by the controller and the system outputs of the quad tiltrotor model as neural network inputs to implement adaptive parameter adjustments for the Extended State Observer (ESO) component responsible for disturbance estimation and the Nonlinear State Error Feedback (NLSEF) control law of the active disturbance rejection controller. Finally, an adaptive attitude control system for the quad tiltrotor UAV is constructed, centered on the ADRC-RBF controller. Subsequently, the efficacy of the attitude control system is validated through simulation, encompassing a range of flight conditions. The simulation results demonstrate that the Integral of Absolute Error (IAE) of the pitch angle response controlled by the ADRC-RBF controller is reduced to 37.4° in comparison to the ADRC controller in the absence of external disturbance in the full-states mode state of the quad tiltrotor UAV, and the oscillation amplitude of the pitch angle response controlled by the ADRC-RBF controller is generally reduced by approximately 50% in comparison to the ADRC controller in the presence of external disturbance. In comparison with the conventional ADRC controller, the proposed ADRC-RBF controller demonstrates superior performance with regard to anti-disturbance capability, adaptability, and tracking accuracy. Full article

The fundus manifestations of pseudopapilledema closely resemble those of optic disc edema, making their differentiation particularly challenging in certain clinical situations. However, rapid and accurate diagnosis is crucial for alleviating patient anxiety and guiding treatment strategies. This study proposes an efficient low-complexity hybrid model, WHA-Net, which innovatively integrates three core modules to achieve precise auxiliary diagnosis of pseudopapilledema. First, the wavelet convolution (WTC) block is introduced to enhance the model’s characterization capability for vessel and optic disc edge details in fundus images through 2D wavelet transform and deep convolution. Additionally, the hybrid attention inverted residual (HAIR) block is incorporated to extract critical features such as vascular morphology, hemorrhages, and exudates. Finally, the Agent-MViT module effectively captures the continuity features of optic disc contours and retinal vessels in fundus images while reducing the computational complexity of traditional Transformers. The model was trained and evaluated on a dataset of 1793 rigorously curated fundus images, comprising 895 normal optic discs, 485 optic disc edema (ODE), and 413 pseudopapilledema (PPE) cases. On the test set, the model achieved outstanding performance, with 97.79% accuracy, 95.55% precision, 95.69% recall, and 98.53% specificity. Comparative experiments confirm the superiority of WHA-Net in classification tasks, while ablation studies validate the effectiveness and rationality of each module’s combined design. This research provides a clinically valuable solution for the automated differential diagnosis of pseudopapilledema, with both computational efficiency and diagnostic reliability. Full article

Coke production is an important source of environmental polycyclic aromatic compounds (PACs), including parent polycyclic aromatic hydrocarbons (PAHs) and their derivatives. The focus near coking plants has primarily been on parent-PAH contamination, with less attention given to highly toxic derivatives. In this study, soil samples were collected from both within and outside of a coking plant. The concentrations of parent-PAHs and their derivatives, including methylated-PAHs, oxygenated-PAHs, and nitrated-PAHs, were examined. Spatial interpolation was employed to determine their spatial distribution patterns. Methods for identifying potential sources and conducting incremental lifetime cancer risk analysis were used. This could achieve a comprehensive understanding of the status of PAC pollution and the associated health risks caused by coke production. The concentrations of total PACs inside the plant ranged from 7.4 to 115.8 mg/kg, higher than those outside (in the range of 0.2 to 65.7 mg/kg). The spatial distribution of parent-PAH concentration and their derivatives consistently decreased with increasing distance from the plant. A significant positive correlation (p < 0.05) among parent-PAHs and their derivatives was observed, indicating relatively consistent sources. Based on diagnostic ratios, the potential emission sources of soil PACs could be attributed to coal combustion and vehicle emissions, while principal component analysis–multiple linear regression further indicated that primary emissions and secondary formation jointly influenced the PAC content, accounting for 60.4% and 39.6%, respectively. The exposure risk of soil PACs was dominated by 16 priority control PAHs; the non-priority PAHs’ contribution to the exposure risk was only 6.4%. Full article

The reserve of litter is expected to be reduced on the forest floors of pine plantations dually for the prevention of high risks of forest fires and with a more practical probability of reuse. Lignin and cellulose are the two key constitutive components in litter residues that account for the highest proportion of carbon but are the last to be fully decomposed. The existing trials started examining the mechanisms behind decomposing these two components in response to the combined driving forces of microclimatic factors, forest structure, and stand properties. However, the results were mostly limited to a local-scale ecosystem, and the evidence was reported to be highly scattered across varied conditions globally. Awareness about the combined effects of the driving forces behind the lignin and cellulose contents in the litter of plantations on a large scale is still scarce. In this study, a total of 60 Pinus tabuliformis Carr. plantations (40-year-old) were investigated for their litter quality, regional meteorological factors, soil properties, and stand structure in a provincial area across Liaoning, northeast China. High lignin (40%–43%) and cellulose contents (15%–20%) were found to be located mainly in stands around the biggest city of Shenyang. Rainfall was a key factor that determined the decomposition, but neither the forest structure nor soil nutrient content generated direct effects on the two litter components. The combined factors of low soil pH (~5.8) and high rainfall (~3.0 mm per day) together mainly accounted for the promotion of natural litter decomposition. Full article

With the gradual increases in the use of wind power and photovoltaic generation, the penetration rate of power electronics has increased in recent years. The inertia characteristics of power-electronic-based power sources are different from those of synchronous generators, making the evaluation of inertia difficult. In this paper, the inertia characteristics of power-electronic-based power sources are analyzed. A measurement-based inertia identification method for power-electronic-based power sources, as well as for high-power-electronic-penetrated power systems, is proposed by fitting the frequency and power data. The inertia characteristics of different control strategies and corresponding control parameters are discussed in a case study. It was proven that the inertia provided by power-electronic-based power sources can be much higher than that provided by a synchronous generator of the same capacity. It was also proven that the inertia provided by power-electronic-based power sources is not a constant value, but changes along with the output power of the sources. Full article

Digital image-correlation (DIC) algorithms rely heavily on the accuracy of the initial values provided by whole-pixel search algorithms for structural displacement monitoring. When the measured displacement is too large or exceeds the search domain, the calculation time and memory consumption of the DIC algorithm will increase greatly, and even fail to obtain the correct result. The paper introduced two edge-detection algorithms, Canny and Zernike moments in digital image-processing (DIP) technology, to perform geometric fitting and sub-pixel positioning on the specific pattern target pasted on the measurement position, and to obtain the structural displacement according to the change of the target position before and after deformation. This paper compared the difference between edge detection and DIC in accuracy and calculation speed through numerical simulation, laboratory, and field tests. The study demonstrated that the structural displacement test based on edge detection is slightly inferior to the DIC algorithm in terms of accuracy and stability. As the search domain of the DIC algorithm becomes larger, its calculation speed decreases sharply, and is obviously slower than the Canny and Zernike moment algorithms. Full article

Black band disease is a globally distributed and easily recognizable coral disease. Despite years of study, the etiology of this coral disease, which impacts dozens of stony coral species, is not completely understood. Although black band disease mats are predominantly composed of the cyanobacterial species Roseofilum reptotaenium, other filamentous cyanobacterial strains and bacterial heterotrophs are readily detected. Through chemical ecology and metagenomic sequencing, we uncovered cryptic strains of Roseofilum species from Siderastrea siderea corals that differ from those on other corals in the Caribbean and Pacific. Isolation of metabolites from Siderastrea-derived Roseofilum revealed the prevalence of unique forms of looekeyolides, distinct from previously characterized Roseofilum reptotaenium strains. In addition, comparative genomics of Roseofilum strains showed that only Siderastrea-based Roseofilum strains have the genetic capacity to produce lasso peptides, a family of compounds with diverse biological activity. All nine Roseofilum strains examined here shared the genetic capacity to produce looekeyolides and malyngamides, suggesting these compounds support the ecology of this genus. Similar biosynthetic gene clusters are not found in other cyanobacterial genera associated with black band disease, which may suggest that looekeyolides and malyngamides contribute to disease etiology through yet unknown mechanisms. Full article

In the past 25 years, a number of efforts have been made toward the development of small molecule interleukin-6 (IL-6) signaling inhibitors, but none have been approved to date. Monosaccharides are a diverse class of bioactive compounds, but thus far have been unexplored as a scaffold for small molecule IL-6-signaling inhibitor design. Therefore, in this present communication, we combined a structure-based drug design approach with carbohydrate building blocks to design and synthesize novel IL-6-signaling inhibitors targeting glycoprotein 130 (gp130). Of this series of compounds, LS-TG-2P and LS-TF-3P were the top lead compounds, displaying IC₅₀ values of 6.9 and 16 µM against SUM159 cell lines, respectively, while still retaining preferential activity against the IL-6-signaling pathway. The carbohydrate moiety was found to improve activity, as N-unsubstituted triazole analogues of these compounds were found to be less active in vitro compared to the leads themselves. Thus, LS-TG-2P and LS-TF-3P are promising scaffolds for further development and study as IL-6-signaling inhibitors. Full article

To improve the satisfaction and acceptance of automatic driving, we propose a deep reinforcement learning (DRL)-based autonomous car-following (CF) decision-making strategy using naturalist driving data (NDD). This study examines the traits of CF behavior using 1341 pairs of CF events taken from the Next Generation Simulation (NGSIM) data. Furthermore, in order to improve the random exploration of the agent’s action, the dynamic characteristics of the speed-acceleration distribution are established in accordance with NDD. The action’s varying constraints are achieved via a normal distribution 3σ boundary point-to-fit curve. A multiobjective reward function is designed considering safety, efficiency, and comfort, according to the time headway (THW) probability density distribution. The introduction of a penalty reward in mechanical energy allows the agent to internalize negative experiences. Next, a model of agent-environment interaction for CF decision-making control is built using the deep deterministic policy gradient (DDPG) method, which can explore complicated environments. Finally, extensive simulation experiments validate the effectiveness and accuracy of our proposal, and the driving strategy is learned through real-world driving data, which is better than human data. Full article

The atomic scale local structures affect the initiation performance of ultra-fine explosives according to the stimulation results of hot spot formation. However, the experimental characterization of local structures in ultra-fine explosives has been rarely reported, due to the difficulty in application of characterization methods having both high resolution in and small damage to unstable organic explosive materials. In this work, X-ray total scattering was explored to investigate the atomic scale local distortion of two widely applicable ultra-fine explosives, LLM-105 and HNS. The experimental spectra of atomic pair distribution function (PDF) derived from scattering results were fitted by assuming rigid ring structures in molecules. The effects of grain refinement and thermal aging on the atomic scale local structure were investigated, and the changes in both the length of covalent bonds have been identified. Results indicate that by decreasing the particle size of LLM-105 and HNS from hundreds of microns to hundreds of nanometers, the crystal structures remain, whereas the molecular configuration slightly changes and the degree of structural disorder increases. For example, the average length of covalent bonds in LLM-105 reduces from 1.25 Å to 1.15 Å, whereas that in HNS increases from 1.25 Å to 1.30 Å, which is possibly related to the incomplete crystallization process and internal stress. After thermal aging of ultra-fine LLM-105 and HNS, the degree of structural disorder decreases, and the distortion in molecules formed in the synthesis process gradually healed. The average length of covalent bonds in LLM-105 increases from 1.15 Å to 1.27 Å, whereas that in HNS reduces from 1.30 Å to 1.20 Å. The possible reason is that the atomic vibration in the molecule intensifies during the heat aging treatment, and the internal stress was released through changes in molecular configuration, and thus the atomic scale distortion gradually heals. The characterization method and findings in local structures obtained in this work may pave the path to deeply understand the relationship between the defects and performance of ultra-fine explosives. Full article