Explore the vast range of titles available.

Prenatal environmental stress damages fetal testicular development, leading to male infertility. However, the precise mechanisms underlying the impact of gestational environmental stress on fetal testicular development require further investigation. This study demonstrates that gestational environmental stressor cadmium exposure caused placental estradiol synthesis inhibition and fetal testicular dysplasia. Gestational estradiol supplementation restores fetal testicular dysplasia caused by environmental stress‐induced placental estradiol synthesis inhibition. Analysis of human placentae and cadmium‐stimulated human primary placental trophoblasts confirmed that ER‐phagy is associated with the inhibition of estradiol synthesis in placentae. Subsequently, the data reveals that environmental stress significantly activates RTN3L‐mediated ER‐phagy. RTN3L ‐deficient cells and placental Rtn3l ‐specific knockout mice confirm that environmental stress‐activated RTN3L‐mediated ER‐phagy inhibited placental estradiol synthesis. Total N6‐methyladenosine level increasing in gestational environmental stress‐exposed placentae. METTL3‐mediated N6‐methyladenosine modification suppression obviously restrains environmental stress‐activated RTN3L‐dependent ER‐phagy. In conclusion, gestational environmental stress activates ER‐phagy by increasing placental Rtn3l mRNA N6‐methyladenosine modification, inhibiting placental estradiol synthesis, and contributing to fetal testicular dysplasia. The study demonstrates the early prevention and treatment of adult male infertility from the perspective of fetal‐derived diseases.

Sepsis is a systemic inflammatory response syndrome attributed to infection, while sepsis‐induced acute lung injury (ALI) has high morbidity and mortality. Here, we aimed to explore the specific mechanism of hypaphorine's anti‐inflammatory effects in ALI. Lipopolysaccharide (LPS) was adopted to construct ALI model both in vivo and in vitro. BEAS‐2B cell viability and apoptosis was testified by the MTT assay and flow cytometry. Reverse transcription‐polymerase chain reaction (RT‐PCR) and enzyme‐linked immunosorbent assay (ELISA) were performed to examine the expression of proinflammatory cytokines (IL‐1β, IL‐6, TNF‐α, and IL‐18), and Western blot was adopted to examine the expression of the apoptosis‐related proteins (Bax, Bcl2, and Caspase3) and the DUSP1/p38/JNK signaling pathway. At the same time, lung injury score, lactate dehydrogenase (LDH) and myeloperoxidase (MPO) activity were monitored. The dry/wet weight method was used to examine lung edema, and the total protein content in BALF was determined to test pulmonary vascular permeability. As the data suggested, hypaphorine inhibited the LPS‐mediated apoptosis of alveolar epithelial cells. What is more, hypaphorine attenuated the expression of inflammatory factors (IL‐1β, IL‐6, TNF‐α, and IL‐18) and inactivated the p38/JNK signaling pathway through upregulating DUSP1 in a dose‐dependent manner. Meanwhile, DUSP1 knockdown weakened the anti‐inflammatory effect of hypaphorine on LPS‐mediated lung injury. Furthermore, hypaphorine also relieved LPS induced ALI in rats with anti‐inflammatory effects. Taken together, hypaphorine prevented LPS‐mediated ALI and proinflammatory response via inactivating the p38/JNK signaling pathway by upregulating DUSP1.

There is strong evidence that obesity is a risk factor for poor semen quality. However, the effects of multigenerational paternal obesity on the susceptibility to cadmium (a reproductive toxicant)-induced spermatogenesis disorders in offspring remain unknown. Here, we show that, in mice, spermatogenesis and retinoic acid levels become progressively lower as the number of generations exposed to a high-fat diet increase. Furthermore, exposing several generations of mice to a high fat diet results in a decrease in the expression of Wt1, a transcription factor upstream of the enzymes that synthesize retinoic acid. These effects can be rescued by injecting adeno-associated virus 9- Wt1 into the mouse testes of the offspring. Additionally, multigenerational paternal high-fat diet progressively increases METTL3 and Wt1 N6-methyladenosine levels in the testes of offspring mice. Mechanistically, treating the fathers with STM2457, a METTL3 inhibitor, restores obesity-reduced sperm count, and decreases Wt1 N6-methyladenosine level in the mouse testes of the offspring. A case-controlled study shows that human donors who are overweight or obese exhibit elevated N6-methyladenosine levels in sperm and decreased sperm concentration. Collectively, these results indicate that multigenerational paternal obesity enhances the susceptibility of the offspring to spermatogenesis disorders by increasing METTL3-mediated Wt1 N6-methyladenosine modification. The mechanisms through which multigenerational paternal obesity affects spermatogenesis in offspring remain poorly understood. Here, the authors show that it affects Wt1 m6A modifications, decreasing the fertility of offspring.

Molybdenum disulfide is considered as one of the most promising two-dimensional semiconductors for electronic and optoelectronic device applications. So far, the charge transport in monolayer molybdenum disulfide is dominated by extrinsic factors such as charged impurities, structural defects and traps, leading to much lower mobility than the intrinsic limit. Here we develop a facile low-temperature thiol chemistry route to repair the sulfur vacancies and improve the interface, resulting in significant reduction of the charged impurities and traps. High mobility >80 cm 2  V −1  s −1 is achieved in backgated monolayer molybdenum disulfide field-effect transistors at room temperature. Furthermore, we develop a theoretical model to quantitatively extract the key microscopic quantities that control the transistor performances, including the density of charged impurities, short-range defects and traps. Our combined experimental and theoretical study provides a clear path towards intrinsic charge transport in two-dimensional dichalcogenides for future high-performance device applications. Impurities in molybdenum disulfide are known to reduce charge mobility to below its intrinsic limit. Here, the authors demonstrate that impurities are associated with lattice defects and that a chemical route can repair sulfur vacancies and improve interface quality with a substrate, enhancing device performance.

Aluminum and its alloy magnetron sputtering targets, owing to their superior electrical/thermal conductivity and robust substrate adhesion, serve as critical materials in advanced electronics and information technologies. It is known that the microstructure of the target, including grain uniformity and crystallographic texture, directly affects the sputtering performance and the quality of the deposited thin film. Despite extensive research efforts, the review paper focused on the microstructure of aluminum target materials is still absent. In that context, the recent progress on the Al alloy target is reviewed, focusing on grain refinement and texture control strategies. The roles of alloying elements, such as Si, Cu, and rare-earth Sc and Nd, are described first. The two conventional manufacturing techniques of fabricating Al targets, including melting and powder metallurgy, are introduced. Then, studies on grain refinement by thermomechanical processing routes (hot/cold rolling, annealing and forging) are summarized. Lastly, texture engineering through deformation and heat treatment protocols (unidirectional/multidirectional rolling, deformation thickness, and composite deformation modes) is reviewed. By establishing the relationship between thermomechanical processing and microstructure, this review provides insights for designing high-performance aluminum targets tailored to next-generation advanced thin-film applications.

Chimeric antigen receptor T (CAR-T) cell therapy has exhibited a substantial clinical response in hematological malignancies, including B-cell leukemia, lymphoma, and multiple myeloma. Therefore, the feasibility of using CAR-T cells to treat solid tumors is actively evaluated. Currently, multiple basic research projects and clinical trials are being conducted to treat lung cancer with CAR-T cell therapy. Although numerous advances in CAR-T cell therapy have been made in hematological tumors, the technology still entails considerable challenges in treating lung cancer, such as on−target, of−tumor toxicity, paucity of tumor-specific antigen targets, T cell exhaustion in the tumor microenvironment, and low infiltration level of immune cells into solid tumor niches, which are even more complicated than their application in hematological tumors. Thus, progress in the scientific understanding of tumor immunology and improvements in the manufacture of cell products are advancing the clinical translation of these important cellular immunotherapies. This review focused on the latest research progress of CAR-T cell therapy in lung cancer treatment and for the first time, demonstrated the underlying challenges and future engineering strategies for the clinical application of CAR-T cell therapy against lung cancer.

The blood-testis barrier (BTB), a unique structure established through intercellular connections of Sertoli cells, establishes a protective microenvironment for spermatogenesis and male fertility. Cadmium (Cd), known for its toxicity, is ubiquitously present in the environment. Here, our findings revealed that Cd exposure compromises BTB integrity, as demonstrated by decreased expression of BTB-associated proteins and elevated D signal /D radius values. Mechanistically, we demonstrated that activation of the CXCL2/CXCR2 axis contributes to Cd-induced BTB impairment, as evidenced by experiments using a CXCR2 inhibition model. As key BTB components, Sertoli cells rely on autophagy to maintain their physiological functions. However, the specific role and mechanism of Sertoli cell autophagy in Cd-induced BTB damage remain unknown. Notably, our results showed that autophagy inhibition aggravated the Cd-induced BTB disruption and testicular CXCL2/CXCR2 axis activation in mice, whereas autophagy activation alleviates Cd-evoked BTB disruption and testicular CXCL2/CXCR2 axis activation. Further verification by Sertoli cell specific Atg5 knockout mouse model showed that the autophagy suppression exacerbated Cd-induced BTB disruption and upregulated the expression of CXCL2. Collectively, our finding points out that ATG5-dependent autophagy in Sertoli cells protects against Cd-induced BTB disruption via perturbing CXCL2/CXCR2 axis. Our study not only reveals a novel molecular mechanism underlying Cd-induced reproductive toxicity but also provides potential therapeutic targets for male infertility intervention.

Flame retardants play a crucial role in improving the flame retardant properties of polymer materials. In recent years, environmental problems caused by flame retardants have attracted widespread attention. It is urgent to use green and effective methods to prepare flame retardant polymers. Bioinspired nanocomposites with layered structures seem to provide effective ideas, but in general, their hydrophilic raw materials limit their applications in certain fields. Here, we prepared biomimetic composites with a layered “brick‐and‐mortar” structure by gravity‐induced deposition using polyimide as the polymer matrix and montmorillonite (MMT) as the filler. The well‐arranged structures of the composite material could isolate oxygen and prevent combustible gases from escaping. The gas barrier performance has been greatly improved, in which the water vapor transmission rate and the oxygen transmission rate decreased by 99.18% and three orders of magnitude, respectively. The flame retardant performance has also been improved, and its limiting oxygen index can reach 67.9%. The polyimide matrix can be converted to water‐insoluble by thermal imidization of water‐soluble poly (amic acid) salt precursors, which endows the composites with low hygroscopicity. The coating containing MMT can protect against polyurethane (PU) foam from fire. During the conical calorimetric test, the coated sample self‐extinguished, and the peak heat release rate, total heat release, and total smoke production are significantly decreased by 53.39%, 40.69%, and 53.03%, respectively. Taking advantage of these properties, this work utilizes a facile method to prepare biomimetic composites with low moisture absorption, excellent gas barrier properties, and flame retardancy, which have great application potential.

Biodiversity loss significantly impacts the stability and functioning of ecosystems, driven by factors such as climate change, human activities, and other influences. Predicting species distributions and conducting conservation gap analyses are essential for identifying key conservation areas, evaluating conservation effectiveness, and highlighting under‐protected areas, thereby providing valuable insights to mitigate biodiversity loss. The Gaoligong Mountains, located within the Three Parallel Rivers of Yunnan Protected Areas (a UNESCO World Natural Heritage Site), serve as an intersection for the biota of the eastern Himalayas, the Indochina Peninsula, and the Hengduan Mountains. The region is a vitally important biological exchange corridor and a long‐standing hotspot for plant geography research. Using the distribution data for 361 rare and endangered plants and eight environmental variables, this study employed the InVEST and random forest (RF) models to determine the current and future potential distribution of these species in the southern Gaoligong Mountains, considering various climate change scenarios combined with currently suitable habitats. The study also evaluated existing protected areas and used a transition matrix to quantify changes in potential habitats. The results show that the current potential suitable habitat in the southern Gaoligong Mountains spans 2987.38 km 2 , with only 23.14% of this area falling within protected zones, leaving a 76.86% protection gap. Additionally, areas with highly suitable habitats are predicted to decline under future climate change scenarios, emphasizing the inadequacy of existing protected areas in comprehensively safeguarding rare and endangered wild plant species. Habitat loss, primarily driven by the expansion of agricultural activities, further exacerbates this issue. To address these conservation gaps, this study recommends prioritizing the integrity of vertical zones when optimizing protected areas, thus ensuring continuous protection for rare and endangered plant species. 生物多样性丧失对生态系统的稳定性和功能产生了重要影响, 其原因包括气候变化、人类活动及其他因素。通过预测物种分布和开展保护空缺分析, 可以帮助确定关键区域, 评估保护措施的有效性, 并识别保护不足的区域, 从而更有效地为减少生物多样性丧失提供科学依据。位于三江并流地区的高黎贡山, 是东喜马拉雅、印度支那半岛和横断山生物区交汇的重要枢纽, 同时也是植物地理学研究的长期热点区域。我们结合361种稀有濒危植物的分布数据和8个环境变量, 利用InVEST和随机森林模型, 分析了高黎贡山南部361种稀有濒危野生植物在当前和未来气候变化情景下的潜在分布及当前适宜生境。我们评估了现有保护区, 并通过转移矩阵量化潜在生境的变化。结果表明, 高黎贡山南部当前的潜在适宜生境面积为2987.38平方公里, 其中仅有23.14%位于保护区内 (意味着有76.86%的区域存在保护空缺) 。此外, 高适宜性区域的面积在气候变化情景下将减少。这突显出现有保护区在为这些稀有濒危野生植物提供全面保护方面的不足。农业活动的扩张成为栖息地丧失的主要驱动因素。我们建议在优化保护区时, 优先考虑垂直植被带的完整性, 以确保稀有濒危植物保护的连续性和有效性。 【翻译：杨勇婧雯和谭运洪】 Biodiversity loss has profound effects on the stability and functioning of ecosystems, driven primarily by climate change and human activities. To improve the protection of endangered plants, we predicted species distributions and conducted a conservation gap analysis to identify critical areas and evaluate the effectiveness of current conservation efforts. Focusing on the southern Gaoligong Mountains, part of the Three Parallel Rivers of Yunnan Protected Areas, we studied the distribution of 361 rare and endangered plants. Using the InVEST and Random Forest models, we analyzed the current and future potential habitats of these plants under various climate scenarios. Our findings show that 2987.38 km² of suitable habitat currently exists in the southern Gaoligong Mountains, yet only 23.14% of this area falls within protected zones, leaving a substantial 76.86% conservation gap. Furthermore, climate change is predicted to reduce the extent of highly suitable habitats, while agricultural expansion is identified as the primary cause of habitat loss. To address these issues, we recommend prioritizing the integrity of the mountain region's vertical vegetation zones when optimizing protected areas to better conserve rare and endangered plant species. 生物多样性减少对生态系统的稳定性和功能有重要影响, 主要原因包括气候变化和人类活动等。为了更好地保护濒危植物, 我们通过预测物种分布和分析保护空缺, 找到了关键区域, 并评估了现有保护措施的有效性。在三江并流地区的高黎贡山南部, 我们研究了361种稀有濒危植物的分布, 结合气候变化预测, 利用InVEST和随机森林模型分析了它们的潜在栖息地情况。研究发现, 目前高黎贡山南部约2987.38平方公里的适宜生境中, 仅有23.14%位于保护区内, 这意味着仍有76.86%的区域缺乏保护。此外, 气候变化将导致高适宜性栖息地面积减少, 而农业活动则是导致栖息地丧失的主要原因。我们建议在优化保护区时, 优先考虑高黎贡山垂直植被带的完整性, 以更好地保护这些珍稀濒危植物的生存环境。 Currently, 76.86% of suitable habitats in the southern Gaoligong Mountains lie outside protected areas, highlighting the urgent need to expand conservation coverage. Highly suitable habitats are projected to decline under future climate scenarios, with agricultural expansion emerging as the leading driver of habitat loss, emphasizing the need for stricter controls on agricultural activities in key ecological regions. Conservation planning should prioritize the integrity of the mountains' vertical vegetation zones to ensure habitat connectivity and stability for rare and endangered plant species. 高黎贡山南部当前的适宜栖息地中, 76.86%的区域未被保护区覆盖, 需要增加保护区面积。 未来气候变化将导致高适宜性栖息地减少, 农业扩张是栖息地丧失的主要驱动因素, 应限制农业开发对关键生态区域的侵占。 建议在规划和调整保护区时, 注重保护高黎贡山垂直植被带的完整性, 以确保稀有濒危植物栖息地的连贯性和稳定性。

Ocean circulation is crucial in redistributing mass and energy on Earth. However, it varies significantly on a seasonal time scale due to external forcing. To quantify the seasonality of ocean circulation, we propose a seasonal circulation index ( SCI ). This index is defined as the normalized maximum deviation from the velocity vector, whose magnitude is the largest in one period. We have substantiated the efficiency of this index using the monsoon wind in the South China Sea (SCS). By utilizing this index, we have obtained the 3D structure of the seasonality of ocean circulation in the SCS. The SCI and the seasonal circulation amplitude ( SCA ) exhibit large values over 0.9 and 0.8 m s -1 in the western boundary current. Alternating southwest-northeastward bands of SCI with high and low values are distributed from the north shelf to the south, especially in the eastern basin. Although SCA decreases significantly with depth, SCI exhibits values higher than 0.7 in both the middle and deep layers, indicating a noteworthy seasonality and middle-layer enhancement in the abyssal basin of the SCS.