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Tissue-clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling reveals neuron circuitry regulating multiple neurotransmitter systems in a whole FFPE mouse brain and is able to be used as the evaluation of disease treatment efficiency. HIF-Clear also supports expansion microscopy and can be performed on a non-sectioned 15-year-old FFPE specimen, as well as a 3-month formalin-fixed mouse brain. Thus, HIF-Clear represents a feasible approach for researching archived FFPE specimens for future neuroscientific and 3D neuropathological analyses.

Renal proximal tubular cells are highly vulnerable to different types of assaults during filtration and reabsorption, leading to acute renal dysfunction and eventual chronic kidney diseases (CKD). The chemotherapeutic drug cisplatin elicits cytotoxicity causing renal tubular cell death, but its executing mechanisms of action are versatile and elusive. Here, we show that cisplatin induces renal tubular cell apoptosis and ferroptosis by disrupting glutathione (GSH) metabolism. Upon cisplatin treatment, GSH metabolism is impaired leading to GSH depletion as well as the execution of mitochondria-mediated apoptosis and lipid oxidation-related ferroptosis through activating IL6/JAK/STAT3 signaling. Inhibition of JAK/STAT3 signaling reversed cell apoptosis and ferroptosis in response to cisplatin induction. Using a cisplatin-induced acute kidney injury (CAKI) mouse model, we found that inhibition of JAK/STAT3 significantly mitigates cisplatin nephrotoxicity with a reduced level of serum BUN and creatinine as well as proximal tubular distortion. In addition, the GSH booster baicalein also reclaims cisplatin-induced renal tubular cell apoptosis and ferroptosis as well as the in vivo nephrotoxicity. In conclusion, cisplatin disrupts glutathione metabolism, leading to renal tubular cell apoptosis and ferroptosis. Rewiring glutathione metabolism represents a promising strategy for combating cisplatin nephrotoxicity.

Ferroptosis is an iron-dependent programmed cell death associated with severe kidney diseases, linked to decreased glutathione peroxidase 4 (GPX4). However, the spatial distribution of renal GPX4-mediated ferroptosis and the molecular events causing GPX4 reduction during ischemia-reperfusion (I/R) remain largely unknown. Using spatial transcriptomics, we identify that GPX4 is situated at the interface of the inner cortex and outer medulla, a hyperactive ferroptosis site post-I/R injury. We further discover OTU deubiquitinase 5 (OTUD5) as a GPX4-binding protein that confers ferroptosis resistance by stabilizing GPX4. During I/R, ferroptosis is induced by mTORC1-mediated autophagy, causing OTUD5 degradation and subsequent GPX4 decay. Functionally, OTUD5 deletion intensifies renal tubular cell ferroptosis and exacerbates acute kidney injury, while AAV-mediated OTUD5 delivery mitigates ferroptosis and promotes renal function recovery from I/R injury. Overall, this study highlights a new autophagy-dependent ferroptosis module: hypoxia/ischemia-induced OTUD5 autophagy triggers GPX4 degradation, offering a potential therapeutic avenue for I/R-related kidney diseases.

In this study, the dissipation and transformation of acetamiprid were investigated during the cowpea pickling process and the toxicity assessment software Ecological Structure Activity Relationship (ECOSAR) and the Toxicity Estimation Software Tool (T.E.S.T.) were used to predict the toxicity of acetamiprid and its transformation products (TPs). The results showed that acetamiprid was rapidly degraded during the pickling process with a degradation rate constant of 0.967 61 and a half-life of (34.95 ± 0.78) d. Four TPs from acetamiprid were found during cowpea pickling process. Among them, the oral lethal doses of TP1 and TP2 in rats were 358.17 and 385.7 mg/kg, respectively, which belonged to the “hazardous” category, and the developmental toxicity of TP1 and TP2 was significantly increased compared with that of acetamiprid. In addition, acetamiprid, TP1, TP2, and TP3 were detected in all real samples. The highest mass concentration of acetamiprid was 473.8 μg/L and the median concentration was 41.1 μg/L. These results reveal the degradation and biotransformation of acetamidine during pickling of cowpea and contribute to a better understanding of the possible health risks of pickling foods.

Abstract Accurate selection of sampling positions is critical in renal artery ultrasound examinations, and the potential of utilizing deep learning (DL) for assisting in this selection has not been previously evaluated. This study aimed to evaluate the effectiveness of DL object detection technology applied to color Doppler sonography (CDS) images in assisting sampling position selection. A total of 2004 patients who underwent renal artery ultrasound examinations were included in the study. CDS images from these patients were categorized into four groups based on the scanning position: abdominal aorta (AO), normal renal artery (NRA), renal artery stenosis (RAS), and intrarenal interlobular artery (IRA). Seven object detection models, including three two-stage models (Faster R-CNN, Cascade R-CNN, and Double Head R-CNN) and four one-stage models (RetinaNet, YOLOv3, FoveaBox, and Deformable DETR), were trained to predict the sampling position, and their predictive accuracies were compared. The Double Head R-CNN model exhibited significantly higher average accuracies on both parameter optimization and validation datasets (89.3 ± 0.6% and 88.5 ± 0.3%, respectively) compared to other methods. On clinical validation data, the predictive accuracies of the Double Head R-CNN model for all four types of images were significantly higher than those of the other methods. The DL object detection model shows promise in assisting inexperienced physicians in improving the accuracy of sampling position selection during renal artery ultrasound examinations.

Background As women with low ovarian reserve embark on the challenging journey of in-vitro fertilisation (IVF) treatment, the choice between natural and mildly stimulated cycles becomes a pivotal consideration. It is unclear which of these two regimens is superior for women with low ovarian reserve. Our study aims to assess the impact of natural cycles on embryo quality and pregnancy outcomes in women with low ovarian reserve undergoing IVF treatment compared to mildly stimulated cycles.Methods This retrospective study enrolled consecutive patients with low ovarian reserve who underwent IVF/intracytoplasmic sperm injection (ICSI) at Guangdong Second Provincial General Hospital between January 2017 and April 2021. The primary outcome for pregnancy rate of 478 natural cycles and 448 mild stimulated cycles was compared. Secondary outcomes included embryo quality and oocyte retrieval time of natural cycles.Results The pregnancy rate in the natural cycle group was significantly higher than that in the mildly stimulated cycle group (51.8% vs. 40.1%, p = 0.046). Moreover, natural cycles exhibited higher rates of available embryos (84.1% vs. 78.6%, p = 0.040), high-quality embryos (61.8% vs. 53.2%, p = 0.008), and utilisation of oocytes (73% vs. 65%, p = 0.001) compared to mildly stimulated cycles. Oocyte retrievals in natural cycles were predominantly performed between 7:00 and 19:00, with 94.9% occurring during this time frame. In natural cycles with high-quality embryos, 96.4% of oocyte retrievals were also conducted between 7:00 and 19:00.Conclusion Natural cycles with appropriately timed oocyte retrieval may present a valuable option for patients with low ovarian reserve.

Inter-turn short circuit fault (ISCF) is the main fault type of dry-type air-core reactors (DARs), and the reactor burnout event caused by winding ISCF seriously threatens the safe and stable operation of the electric power system. In order to effectively curb the further worsening of ISCF in DARs, a fault detection method based on frequency response analysis was proposed. First, the effect of ISCF on the frequency response curve of the windings was investigated based on the distributed parameter model of DARs. Then, four sets of eigenvalues were proposed for ISCF diagnosis based on the influence law and curve data analysis theory. Finally, based on the eigenvalues, the support vector machine model optimized by the sparrow search algorithm was used to effectively classify the degree of ISCF of the reactor, and the accuracy reached 96%. Furthermore, a test platform was built based on the theoretical analysis for experimental verification, and the test results are consistent with the simulation results. Hence, the method proposed in this paper could effectively classify the ISCF and its severity in DARs. The research in this paper could provide effective guidance for the diagnosis of ISCF in DARs.

The topological bound states are limited to one pair in traditional one-dimensional (1D) topological chiral models as the winding number can only take the value of 0 or 1. It was increased to 2 or 3 via long-range couplings (LRCs) that were restricted to second- or third-order in recent experimental or theoretical researches. How to generate larger winding number to manipulate more topological bound states remains a challenge. Here, we propose an effective method by introducing arbitrary Nth order LRC stronger than the sum of other order couplings. The resulting winding number has been computed by getting the winding loop's envelope in parameter space. The coupling-inverted 1D photonic topological insulators supporting up to three pairs of highly localized multiple topological bound states are realized by fabricating photonic lattices with multi-layer waveguide arrays. Furthermore, these topological bound states are closely spaced, offering a promising implementation approach of multimode topological lasers in gain media. Our work highlights the advantages of LRCs in manipulating the topological phases of matter.

By anchoring the lower rollers and dynamically adjusting the upper roller’s downfeed of a pyramid roll bender, one can achieve the precise bending of a workpiece into a desired planar form characterized by variable curvature. To ensure the seamless processing of individual cross sections without impinging upon adjacent areas, critical roller spacings are identified through theoretical mechanics analyses. The reaction force exerted on the top roller is calculated by integrating the desired curvature into the elastoplastic constitutive equation and subsequently deriving a dynamic adjustment of the downfeed from quasi-static finite element simulations. This preliminary downfeed protocol undergoes refinement to mitigate discrepancies between the targeted and the actual curvatures. Numerical instances demonstrate that the application of roller configurations, as outlined herein, yields a product profile that closely mirrors the intended curve. This congruence can be further improved with an additional iteration; however, subsequent iterations are seen to yield negligible improvements, indicating a rapid convergence of this algorithm.

Background:Systemic inflammatory regulators have been associated with preeclampsia (PE) during pregnancy; however, there is inconsistent evidence from animal models and observational results.Methods:Using summary data from genome-wide association studies (GWASs), we performed a bidirectional Mendelian randomization (MR) analysis of two samples of systemic inflammatory regulators (n = 8,186) and PE (n = 267,242) individuals of European ancestry. As our primary analysis, we used the random-effects inverse-variance weighted (IVW) approach. Sensitivity and pleiotropy analyses were conducted using the MR–Egger method, weighted median, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and Cochran’s Q test.Results:The results indicate that there is a correlation between a higher circulating level of tumor necrosis factor alpha (TNF-α) and interleukin-9 (IL-9) and an increased risk of PE (odds ratio [OR] = 1.32, 95% confidence interval [CI] = 1.09–1.60, p = 0.004 and OR = 1.28, 95% CI: 1.02–1.62, p = 0.033, respectively). Conversely, lower levels of stem cell growth factor beta (SCGF-β) (OR = 0.89, 95% CI: 0.80–0.99, p = 0.027) and interleukin-5 (IL-5) (OR = 0.80, 95% CI: 0.65–0.98, p = 0.030) are linked to an increased risk of PE. The macrophage migration inhibitory factor (MIF) is the downstream inflammatory regulator of PE, according to reverse magnetic resonance imaging studies.Conclusion:Our study suggests that SCGF-β, IL-5, IL-9, and TNF-α causally affect the PE risk, while PE is causally associated with MIF. Further studies are needed to validate these biomarkers in managing PE.

ABSTRACT A series of low‐carbon fly ash cenosphere plates was prepared using solid waste based cementitious material as binder through a simple process; meanwhile, effects of cenosphere's particle size and size distribution on microstructure and properties were investigated. In the range of 20–200 mesh, as particle size decreases, sound absorption performance decreases while strength improves. Appropriate particle grading can effectively improve the compressive strength, but it will lead to a significant decrease in sound absorption performance. Samples prepared from fly ash cenosphere with a particle size of 20–40 mesh show good sound absorption performance: when the cavity size is 0 mm, the maximum sound absorption coefficient is 0.64 and the average value is 0.36 in the range of 50–1 600 Hz; when the cavity size is 100 mm, sound absorption coefficient at 100 Hz is 0.47, the maximum sound absorption coefficient in the range of 50–1 600 Hz is 0.90, and the average value is 0.57 in the range of 100–500 Hz. The prepared low‐carbon fly ash cenosphere plates show excellent sound absorption performance at low‐frequency and are expected to have broad application prospects in low‐frequency noise reduction and absorption.

Summary: Visual perceptual learning (VPL), experience-induced gains in discriminating visual features, has been studied extensively and intensively for many years, its profile in feature space, however, remains unclear. Here, human subjects were trained to perform either a simple low-level feature (grating orientation) or a complex high-level object (face view) discrimination task over a long-time course. During, immediately after, and one month after training, all results showed that in feature space VPL in grating orientation discrimination was a center-surround profile; VPL in face view discrimination, however, was a monotonic gradient profile. Importantly, these two profiles can be emerged by a deep convolutional neural network with a modified AlexNet consisted of 7 and 12 layers, respectively. Altogether, our study reveals for the first time a feature hierarchy-dependent profile of VPL in feature space, placing a necessary constraint on our understanding of the neural computation of VPL.

Lack of social interaction is associated with a heightened sense of loneliness and, in turn, poorer psychological well-being. Despite the prevalence of communicating with others virtually even when physically alone, whether the social interaction--loneliness--well-being relationship is different between face-to-face and virtual interactions and between younger and older adults is relatively understudied. This 21-day diary study examined this question among younger (n = 91; M[subscript age] = 22.87) and older (n = 107; M[subscript age] = 64.53) Hong Kong participants during the early stage of the COVID-19 pandemic (March-May 2020). We found significant indirect effects of shorter face-to-face interaction time on poorer psychological well-being via a heightened sense of loneliness at the within-person level only among younger adults and at the between-person level only among older adults. Independent of loneliness, spending more time with others on virtual interactions was associated with better psychological well-being only among older adults. Taken together, while the mechanisms may be different across age groups, face-to-face interaction remains an effective way to reduce loneliness and enhance psychological well-being even at times when it is discouraged (e.g., pandemic). Although virtual interaction does not reduce loneliness, its positive impact on older adults' well-being sheds light on the utility of promoting technological acceptance in late adulthood.

Abstract Anomalous Floquet topological insulators with vanishing Chern numbers but supporting chiral edge modes are attracting more and more attention. Since the existing anomalous Floquet topological insulators usually support only one kind of chiral edge mode even at a large lattice size, they are unscalable and unapplicable for multistate topological quantum systems. Recently, fractal topological insulators with self-similarity have been explored to support more nontrivial modes. Here, we demonstrate the first experimental realization of fractal photonic anomalous Floquet topological insulators based on dual Sierpinski carpet consisting of directional couplers using the femtosecond laser direct writing. The fabricated lattices support much more kinds of chiral edge states with fewer waveguides and enable perfect hopping of quantum states with near unit transfer efficiency. Instead of zero-dimensional bound modes for quantum state transport in previous laser direct-written topological insulators, we generate multiple propagating single-photon chiral edge states in the fractal lattice and observe high-visibility quantum interferences. These suggest the successful realization of highly indistinguishable single-photon chiral edge states, which can be applied in various quantum operations. This work provides the potential for enhancing the multi-fold manipulation of quantum states, enlarging the encodable quantum information capacity in a single lattice via high-dimensional encoding and many other fractal applications.

Introduction: The R-loop is a naturally formed three-strand nucleic acid structure that recently has been reported to participate in multiple biological processes and helped answer some previously unexplained scientific questions. Meiosis process involves multiple chromatin-related events such as DNA double-stranded breaks (DSB) formation, repairing and transcriptional dynamics. Objectives: Explore the regulatory roles and physiological functions of R-loops in the mammalian meiosis process. Methods: In our study, using genome-wide S9.6 CUT & Tag seq, we first mapped the genomic distribution and dynamic changes of R-loop during the meiotic process in mice, from spermatogonia to secondary spermatocytes. And we further explore the role of R-loop in physiological conditions by constructing conditional knockout mice of Rnaseh1, which deleted the R-loop endonuclease before meiosis entry. Results: R-loop predominantly distributes at promoter-related regions and varies across different meiotic stages. By joint analysis with the corresponding transcriptome, we found that the R-loop was closely related to transcription during the meiotic process. The high frequency of promoter-related R-loop in meiotic cells is usually accompanied by high transcription activity, and we further verified this in the leptotene/zygotene to the pachytene transition process. Moreover, the lack of RNase H1 caused sterility in male mice with R-loop accumulation and abnormal DSB repair in spermatocytes. Further analysis showed that abnormal R-loop accumulation in the leptotene/zygotene stages influenced transcriptional regulation in the pachytene stage. Conclusion: The mutual regulation of the R-loop and transcription plays an essential role in spermatogenesis. And R-loop is also important for the normal repair process of DSB during meiosis.

Taking cultural ecology as the carrier of tourism resources, it fully embodies the significance of the synergistic development of cultural tourism ecology for the innovation of the cultural tourism model. The article establishes a cultural tourism ecological synergy model by integrating cultural ecology and cultural tourism under the guidance of the theory of the life cycle of tourist places and industrial innovation. Taking the nine provinces of the Yellow River as the research object, its cultural tourism data are collected and pre-processed, cultural tourism keywords are extracted by the TextRank algorithm, and the LDA model is established to obtain cultural tourism themes. The Skip-gram model was combined with the GCN network to establish a cultural tourism emotional image perception model, and the Moran index and nearest-neighbor index were introduced to analyze the spatial structure and regional evolution of cultural tourism attractions. The keywords of cultural tourism are mainly embodied in ecology and culture, which all appear more than 1,000 times, and the percentage of tourists’ most concerned cultural tourism themes is 22.15%, and most of the nearest neighbor indices of the spatial structure of the attractions at different levels are less than 1, which is cohesive. The Moran index of tourists’ footprints in 2022 is 0.106, the footprint coverage rate is 0.26 percentage points higher than that in 2012, and tourists’ positive emotional evaluation of cultural tourism destinations reaches 80%. Based on cultural ecology, realizing the synergistic development of cultural tourism and ecology is the way to innovate cultural tourism.