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Mutations in COL4A3 , COL4A4 and COL4A5 genes lead to Alport syndrome (AS). However, pathogenic variants in some AS patients are not detected by exome sequencing. The aim of this study was to identify the underlying genetic causes of five unrelated AS probands with negative next-generation sequencing (NGS) test results. Urine COL4A3–5 mRNAs were analyzed in the probands with an uncertain inherited mode of AS, and COL4A5 mRNA of skin fibroblasts was analyzed in the probands with X-linked AS. RT-PCR and direct sequencing were performed to detect mRNA abnormalities. PCR and direct sequencing were used to analyze the exons with flanking intronic sequences corresponding to mRNA abnormalities. Six novel deep intronic splicing variants in COL4A4 and COL4A5 genes that cannot be captured by exome sequencing were identified in the four AS probands. Skipping of an exon was caused by an intronic variant, and retention of an intron fragment caused by five variants. In the remaining AS proband, COL4A5 variants c.2677 + 646 C > T and r.2678_r.2767del were detected at the DNA and RNA level, respectively, whereas it is unclear whether c.2677 + 646 C > T may not lead to r.2678_r.2767del. Our results reveal that mRNA analysis for AS genes from either urine or skin fibroblasts can resolve genetic diagnosis in AS patients with negative NGS results. We recommend analyzing COL4A3–5 mRNA from urine as the first choice for these patients because it is feasible and non-invasive.

Background Chemotherapy can induce premature ovarian insufficiency (POI). POI causes multiple sequelae and is currently incurable. As shown in our previous studies, systemically transplanted human amnion-derived mesenchymal stem cells (hAD-MSCs) home to ovaries with chemotherapy-induced POI and subsequently reduce ovarian injury and improve ovarian function in rats with POI. However, the cellular mechanisms that direct the migration and homing of hAD-MSCs to ovaries with chemotherapy-induced POI are incompletely understood. This study investigated the role of the SDF-1/CXCR4 axis in the migration and homing of systemically transplanted hAD-MSCs to ovaries with chemotherapy-induced POI and its relevant downstream signalling pathways. Methods CXCR4 expression in hAD-MSCs was assessed using Western blotting and immunofluorescence staining. hAD-MSC migration was tested using Transwell migration assays. SDF-1 levels were detected using ELISA. Seventy-two female SD rats were randomly divided into the control, POI, hAD-MSCs and hAD-MSCs + AMD3100 groups. Cyclophosphamide was used to establish rat POI models. For inhibitor treatment, hAD-MSCs were pretreated with AMD3100 before transplantation. PKH26-labeled hAD-MSCs were injected into the tail vein of POI rats 24 h after chemotherapy. After hAD-MSC transplantation, the homing of hAD-MSCs to ovaries and ovarian function and pathological changes were examined. We further investigated the molecular mechanisms by detecting the PI3K/Akt and ERK1/2 signalling pathways. Results hAD-MSCs expressed CXCR4. SDF-1 induced hAD-MSC migration in vitro. SDF-1 levels in ovaries and serum were significantly increased in rats with chemotherapy-induced POI, and ovaries with POI induced the homing of hAD-MSCs expressing CXCR4. Blocking the SDF-1/CXCR4 axis with AMD3100 significantly reduced the number of hAD-MSCs homing to ovaries with POI and further reduced their efficacy in POI treatment. The binding of SDF-1 to CXCR4 activated the PI3K/Akt signalling pathway, and LY294002 significantly inhibited hAD-MSC migration induced by SDF-1 in vitro. Moreover, inhibition of the PI3K/Akt signalling pathway significantly reduced the number of systemically transplanted hAD-MSCs homing to chemotherapy-induced ovaries in rats with POI. Conclusions SDF-1/CXCR4 axis partially mediates the migration and homing of systemically transplanted hAD-MSCs to the ovaries of rats with chemotherapy-induced POI, and the PI3K/Akt signalling pathway might be involved in the migration and homing of hAD-MSCs mediated by the SDF-1/CXCR4 axis.

Quantifying temporal and spatial changes in reactive nitrogen (Nr) losses from a watershed and exploring its main drivers are the key to watershed water quality improvements. Huge Nr losses continue to threaten the safety of the water environment in the Taihu Lake Basin (TLB). Here, the InVEST and GeoDetector models were combined to estimate Nr losses in the TLB from 1990 to 2020 and explore driving forces. Different scenarios for Nr losses were compared, showing that Nr loss peaked at 181.66 × 10 3 t in 2000. The key factors affecting Nr loss are land use, followed by elevation, soil, and slope factors, and their mean q- values were 0.82, 0.52, 0.51, and 0.48, respectively. The scenario analysis revealed that Nr losses increased under the business-as-usual and economic development scenarios, while ecological conservation, increased nutrient use efficiency, and reduced nutrient application all contribute to a reduction in Nr losses. The findings provide a scientific reference for Nr loss control and future planning in the TLB.

Through the analysis of hot oil carrying theory, the problem of oil film heat accumulation in hydrostatic bearing can be revealed, so as to avoid serious lubrication failure caused by heat accumulation. In this paper, the hot oil carrying factor is defined and the mathematical model of the thermal oil carrying characteristics of the oil film is established by taking the beveled double rectangular oil pad hydrostatic bearing as the object, and the hot oil carrying law under different working conditions is obtained by changing the inclination angle of the beveled oil pad at 0.0230°, 0.0250° and 0.0280°, respectively. Theoretical calculations and simulation studies show that within the range of the circumferential inclination of the oil pad with better dynamic pressure effect of the bearing, the inclination has little effect on the oil film hot oil carrying. When the speed of the workbench is lower than 10r/min, no oil film hot oil carrying phenomenon occurs. When the speed is in the range of 10r/min-100r/min, a part of the load will cause the phenomenon of oil film hot oil carrying. And when the speed exceeds 100r/min, the heat accumulation of the oil film is the most serious at this time. There are many reasons for the lubrication failure of hydrostatic bearings, and hot oil carrying is a new research direction, this paper starts from the oil film heating mechanism of beveled oil pads hydrostatic bearings, and describes the phenomenon of hot oil carrying.

Endometriosis (EMs) is defined as the presence of tissue somewhat resembling endometrial glands and stroma outside the uterus; the retrograded endometrium grows in the peritoneal cavity and elicits fibrosis. Ferroptosis is a recently discovered form of programmed cell death, which is iron-dependent. The induction of ferroptosis has been found to participate in fibrosis. However, the relationship between EMs fibrosis and ferroptosis remains unknown. In this study, we confirmed that the iron content in ectopic stromal tissue in ovarian EMs is significantly increased. We explored the role of iron-induced ferroptosis in the pathogenesis of ovarian EMs fibrosis for the first time. We found that ferroptosis in ectopic tissues was significantly enhanced than that in eutopic tissues. Furthermore, we performed in vivo drug screening and found that ferroptosis induced by ferric ammonium citrate (FAC) could aggravate fibrosis. To clarify the mechanism of this process, the stromal composition of human uterine endometrium and endometrial tissue was characterized. Fibroblast-specific protein-1 was used for fibroblasts, smooth muscle actin alpha for myofibroblasts, and platelet-derived growth factor receptor beta (CD140b) for mesenchymal stromal cells (MSCs). The results demonstrated that the percentage of myofibroblasts was higher and the portion of MSCs was lower in ectopic endometrial stroma than those in eutopic endometrium. Moreover, the proportion of MSCs decreased significantly and the percentage of myofibroblasts increased considerably after FAC treatment in vitro . However, disruption of intracellular iron levels or ferroptosis via chelation of intracellular iron deferoxamine mesylate or ferroptosis inhibitor ferrostatin-1 could reverse this process, indicating that iron-induced ferroptosis plays a vital role in ovarian EMs fibrosis. Considering that iron accumulation can feed the Fenton reaction to generate unquenchable amounts of free radicals, causing ferroptosis and tissue damage and thereby contributing to fibrosis, we validated the underlying mechanism that excess iron can facilitate fibrotic responses. Collectively, these data provide evidence that supernumerary iron is a key regulator in promoting MSCs ferroptosis and inducing ovarian EMs fibrosis.

Background/Objectives: Equitable access to childhood vaccines remains a challenge in many low- and middle-income countries. This study assessed coverage of WHO-recommended childhood vaccines in Cambodia and the Philippines, focusing on urban–rural and wealth disparities, and examined maternal demographic and socioeconomic factors influencing vaccination coverage. Methods: Cross-sectional data from Demographic and Health Surveys from Cambodia (2000–2021/22) and the Philippines (2003–2022) were used. Descriptive analyses were performed to elucidate vaccination coverage trends (BCG, hepatitis B birth dose, DTP, OPV, PCV, and measles). Urban–rural and wealth-related disparities were assessed by calculating absolute differences and Slope Index of Inequality. Logistic regression was used to analyze the impact of maternal demographics and socioeconomic status on vaccination coverage. Results: Cambodia showed significant increases in BCG, DTP, and OPV coverage over the past two decades, whereas those coverage in the Philippines declined slightly since 2017. In 2022, 75.2% of Filipino children received the BCG and hepatitis B (birth dose) vaccines, and around two-thirds completed DTP, OPV, and PCV vaccinations on schedule, lower than the rates in Cambodia. Only half of the children completed measles vaccination in both countries. Urban–rural disparities declined over time in both countries, but wealth inequalities persisted and widened in the Philippines between 2017 and 2022. Women with higher education attainment, from a wealthy household and having fewer children, was associated with increased likelihood of completing childhood vaccinations in both countries. Conclusions: Persistent socioeconomic disparities in childhood vaccination in low- and middle-income countries highlight the need for targeted pro-poor and community-based strategies to ensure equitable access.

The electric vertical takeoff and landing (eVTOL) aircraft shows great potential for rapid military personnel deployment on the battlefield. However, its susceptibility to control loss, complex crashes, and extremely limited bottom energy-absorbing space demands higher comprehensive crashworthiness of its subfloor thin-walled structures. This study investigated the energy absorption capacity of novel concave polygonal carbon fiber reinforced plastics (CFRP) tubes under multi-angle collisions. Quasi-static compression experiments and finite element simulations were conducted to assess the failure mode and energy absorption. The influences of cross-section shapes, loading conditions, and geometry parameters on crashworthiness metrics were further analyzed. The results revealed that, under the similar weight, concave polygonal tubes exhibited superior energy absorption under axial loads compared to regular polygonal and circular tubes, attributed to the increased number of axial splits. However, both regular and concave polygonal tubes, particularly the latter, demonstrated reduced oblique energy absorption compared to traditional square tubes with the increasing ratio of SEA value decreased from 20%−16%. Notably, this reduction in energy absorption can be compensated for by the implementation of inward and outward crusher plugs, and with them, the concave polygonal tubes demonstrated outstanding overall crashworthiness performance under multiple loading conditions. This concave cross-sectional design methods could serve as a guidance for the development of the eVTOL subfloor.

With the rapid development of advanced technologies in the Internet of Things era, higher requirements are needed for next‐generation electronic devices. Fortunately, organic thin film transistors (OTFTs) provide an effective solution for electronic skin and flexible wearable devices due to their intrinsic features of mechanical flexibility, lightweight, simple fabrication process, and good biocompatibility. So far considerable efforts have been devoted to this research field. This article reviews recent advances in various promising and state‐of‐the‐art OTFTs as well as related integrated circuits with the main focuses on: (I) material categories of high‐mobility organic semiconductors for both individual transistors and integrated circuits; (II) effective device architectures and processing techniques for large‐area fabrication; (III) important performance metrics of organic integrated circuits and realization of digital and analog devices for future smart life; (IV) applicable analytical models and design flow to accelerate the circuit design. In addition, the emerging challenges of OTFT‐based integrated circuits, such as transistor uniformity and stability are also discussed, and the possible methods to solve these problems at both transistor and circuit levels are summarized. Organic thin film transistors (OTFTs) hold great potential for future smart life due to their intrinsic features of mechanical flexibility, lightweight, simple fabrication process, and good biocompatibility. This article reviews recent advances in various promising and state‐of‐the‐art OTFTs as well as related integrated circuits with the main focus on high‐performance material categories, device architectures and processing techniques, digital and analog devices, and analytical models and design flow. Additionally, the emerging challenges of OTFT‐based integrated circuits and possible solutions are also discussed.

As is well known, intelligence and efficiency are important development directions for modern agriculture. The harvesting header, as key components of crop harvesters, have significant implications for achieving intelligent control of their working height, which has a notable impact on reducing harvest loss. To understand the current state of intelligent control technology for the working height of a crop harvesting header, and to explore their application potential, this article provides a relatively systematic literature review. Firstly, we analyzed the structure and principle of the harvesting header of typical grain and oil crops such as rice and peanuts. Secondly, we briefly described the current methods for controlling the working height of the harvesting header. They mainly use two methods: mechanical profiling and electro-hydraulic profiling. Thirdly, we focused on researching and analyzing the measurement methods and control algorithms for the working height of the harvesting header. Finally, we pointed out the problems in the current height control of the harvesting header. These problems mainly include insufficient measurement accuracy of working height in complex terrain, slow response and large delay of working height hydraulic control system, incompatibility between working height control models and strategies, and relatively single working height measurement methods.