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Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca 2+ -mobilizing second messenger which uniquely mobilizes Ca 2+ from acidic endolysosomal organelles. However, the molecular identity of the NAADP receptor remains unknown. Given the necessity of the endolysosomal two-pore channel (TPC1 or TPC2) in NAADP signaling, we performed affinity purification and quantitative proteomic analysis of the interacting proteins of NAADP and TPCs. We identified a Sm-like protein Lsm12 complexed with NAADP, TPC1, and TPC2. Lsm12 directly binds to NAADP via its Lsm domain, colocalizes with TPC2, and mediates the apparent association of NAADP to isolated TPC2 or TPC2-containing membranes. Lsm12 is essential and immediately participates in NAADP-evoked TPC activation and Ca 2+ mobilization from acidic stores. These findings reveal a putative RNA-binding protein to function as an NAADP receptor and a TPC regulatory protein and provides a molecular basis for understanding the mechanisms of NAADP signaling. Nicotinic acid adenine dinucleotide phosphate (NAADP) potent Ca 2+ mobilizing second messenger which uniquely triggers Ca 2+ release from acidic endolysosomal organelles. Here the authors identify Lsm12 as an NAADP receptor essential for NAADP-evoked Ca 2+ release from lysosomes via NAADP binding on its Lsm domain.

Two studies demonstrate that the methyltransferase KMT2D, which is recurrently mutated in several types of human B cell lymphoma, suppresses tumorigenesis by altering the epigenetic landscape of B cells; Kmt2d deletion in mice perturbs normal B cell development. Mutations in the gene encoding the KMT2D (or MLL2) methyltransferase are highly recurrent and occur early during tumorigenesis in diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL). However, the functional consequences of these mutations and their role in lymphomagenesis are unknown. Here we show that FL- and DLBCL-associated KMT2D mutations impair KMT2D enzymatic activity, leading to diminished global H3K4 methylation in germinal-center (GC) B cells and DLBCL cells. Conditional deletion of Kmt2d early during B cell development, but not after initiation of the GC reaction, results in an increase in GC B cells and enhances B cell proliferation in mice. Moreover, genetic ablation of Kmt2d in mice overexpressing Bcl2 increases the incidence of GC-derived lymphomas resembling human tumors. These findings suggest that KMT2D acts as a tumor suppressor gene whose early loss facilitates lymphomagenesis by remodeling the epigenetic landscape of the cancer precursor cells. Eradication of KMT2D-deficient cells may thus represent a rational therapeutic approach for targeting early tumorigenic events.

Background This study investigated the effects of authoritarian filial piety (AFP) and caregiver self-efficacy on the caregiving experience of adult children of physically impaired older adults. Socio-cultural stress and coping model was applied to test the influence of AFP on caregiver gains. Methods A total of 601 Chinese adult children caregivers and care-recipient dyads participated in this cross-sectional study in 2021. Four instruments were used to collect data: the 4-item Zarit Burden Interview, Positive Aspects of Caregiving Scale, Caregiver Task Inventory Scale, and Authoritarian Filial Piety Scale. All mediation and moderated mediation effects were estimated using SPSS 26.0. Results Caregiver self-efficacy was found to not only mediate but also help family caregivers convert their burden into positive gains. AFP moderates the association between caregiver burden and self-efficacy, as well as between caregiver burden and caregiver gains. Conclusions This study provides valuable insights into filial piety, elucidating AFP’s comprehensive impact on cognitive appraisals of caregiving. Culturally sensitive psychoeducational therapy, addressing AFP expectations and boosting caregiver self-efficacy, is recommended to enhance positive caregiving outcomes.

The surface urban heat island (SUHI) phenomenon has become increasingly severe due to the combined effects of global warming and rapid urban expansion, and the difference between urban and rural thermal environments has increased significantly. This trend has profound impacts on social, economic, and ecological environments. Research related to SUHI has achieved fruitful results; however, quantitative research methods for SUHI have not been unified with standards and systems, which will certainly affect the comparability of the results of SUHI research. Few studies have combined and compared multiple SUHI methods. Therefore, we designed a study of the Yangtze River Delta (YRD) urban agglomeration as a test case to quantitatively analyze the differences between SUHI results in different urban and rural contexts based on five different SUHI research methods. It was found that (1) there were significant differences in the SUHI intensity results among the different methods. The maximum difference in the SUHI intensity obtained by different methods can be up to 6 °C. The lowest SUHI intensity was observed during the day in the urban–buffer method, and the lowest SUHI intensity was observed at night in the urban–water method. (2) Different methods affected the distribution of SUHI areas and their evolutionary characteristics. The NHI (no heat island), WCI (weak cold island), and WHI (weak heat island) zones were larger, with proportions exceeding 70%. The expansion range of the heat island zone during the daytime was mainly in the west and north of the YRD urban agglomeration, whereas the expansion of the heat island range at night was mainly concentrated in the center and south. (3) The trend changes observed using different methods were significantly different. When we applied the urban–buffer and municipal–nonmunicipal methods, most cities showed an upward trend. However, when the other methods were applied, most cities exhibited a downward trend. The differences in trend results owing to the choice of different methods were greater with respect to values in the summer months and smaller in the winter months.

To address the challenges of power fluctuations caused by the integration of distributed generation (DG) and the difficulty in simultaneously managing peak-valley load regulation due to diverse user energy demands in a microgrid system, this paper presents a coordinated optimal configuration method for serving a hybrid energy storage system (HESS), which explicitly considers the differentiated requirements from both the supply-side and the demand-side. In the presented method, an improved empirical mode decomposition (EMD) method is first presented to decompose the DG power into high-frequency, medium-frequency, and low-frequency bands. Based on the complementary technical and economic characteristics of different energy storage types, a coordinated regulation strategy for HESS in the multiple time-frequency domains is developed. Second, a coordinated optimal configuration model for HESS is further established. This model integrates key performance indicators, including maximum fluctuation and renewable energy utilization rate on the supply-side and the peak-valley difference reduction rate on the demand-side. Finally, a distributed optimization algorithm based on an improved alternating direction method of multipliers (ADMM) is developed to solve the coordinated configuration model. The experimental results demonstrate that the presented method can effectively smooth the DG power fluctuations and reduce the load peak-valley difference. The renewable energy utilization rate reaches 100%, and the peak-valley difference reduction rate reaches approximately 80%. The presented method successfully achieves the coordinated optimal configuration of HESS on both the supply and demand sides, providing a theoretical underlying infrastructure for the configuration of energy storage in the microgrid system with high penetration of renewable energy.

Gravitational microlensing is a unique method for discovering cold planets across a broad mass range. Reliable statistics of the microlensing planets require accurate sensitivity estimates. However, the impact of the degeneracies in binary-lens single-source (2L1S) models that affect many actual planet detections is often omitted in sensitivity estimates, leading to potential self-inconsistency of the statistics studies. In this work, we evaluate the effect of the 2L1S degeneracies on planetary sensitivity by simulating a series of typical microlensing events and comprehensively replicating a realistic planet detection pipeline, including the anomaly identification, global 2L1S model search, and degenerate model comparison. We find that for a pure-survey statistical sample, the 2L1S degeneracies reduce the overall planetary sensitivity by 5%–10%, with the effect increasing at higher planet-host mass ratios. This bias leads to an underestimation of planet occurrence rates and a flattening of the inferred mass-ratio function slope. This effect will be critical for upcoming space-based microlensing surveys like the Roman or Earth 2.0 missions, which are expected to discover O(103) planets. We also discuss the computational challenges and propose potential approaches for future applications.

RALY is a multifunctional RNA-binding protein involved in cancer metastasis, prognosis, and chemotherapy resistance in various cancers. However, the molecular mechanism of which is still unclear. We have established RALY overexpression cell lines and studied the effect of RALY on proliferation and apoptosis in HeLa cells. Then we used RNA-seq to analyze the transcriptomes data. Lastly, RT-qPCR experiments had performed to confirm the RNA-seq results. We found that the overexpression of RALY in HeLa cells inhibited proliferation. Moreover, the overexpression of RALY changed the gene expression profile, and the significant upregulation of genes involved immune/inflammatory response related biological process by NOD-like receptor signaling pathway cytokine-cytokine receptor interaction. The significant downregulation genes involved innate immune response by the Primary immunodeficiency pathway. Notably, IFIT1, IFIT2, IFTI3, IFI44, HERC4, and OASL expression had inhibited by the overexpression of RALY. Furthermore, RALY negatively regulates the expression of transcription factors FOS and FOSB. Notably, we found that 645 alternative splicing events had regulated by overexpression of RALY, which is highly enriched in transcription regulation, RNA splicing, and cell proliferation biological process by the metabolic pathway. We show that RALY regulates the expression of immune/inflammatory response-related genes via alternative splicing of FOS in HeLa cells. The novel role of RALY in regulating immune/inflammatory gene expression may explain its function in regulating chemotherapy resistance and provides novel insights into further exploring the molecular mechanism of RALY in regulating cancer immunity and chemo/immune therapies.

To enhance the cultivation and utility of alfalfa ( Medicago sativa ) in calcium-rich environments, we assessed the germination, growth, and physiological responses of seven alfalfa varieties—Crown, Dieter, PANGO, Gladiator, Victoria, WL525, and Magnum 801—under varying calcium chloride (CaCl 2 ) concentrations (0, 5, 25, and 50 mmol·L −1 ). Germination indices, root and shoot growth, enzyme activities, and osmotic regulation parameters were analyzed to evaluate adaptive responses to calcium stress. Our results showed that alfalfa adapts to calcium stress by increasing root length, enhancing enzyme activities, regulating osmotic substance content, and reducing malondialdehyde levels, thereby striving to maintain stable dry matter content. However, the extent of these adaptive responses varied among the different varieties. Based on a comprehensive evaluation, the calcium adaptability of the varieties ranked in the following order: Gladiator > Victoria > Dieter > Magnum 801 > WL525 > Crown > PANGO. Notably, calcium concentrations of 5–25 mmol·L −1 were found to be optimal for germination, physiological regulation, and growth, whereas higher concentrations (50 mmol·L −1 ) induced oxidative stress and impaired growth. This study highlights the role of exogenous calcium in enhancing physiological resilience and provides a robust framework for selecting calcium-tolerant alfalfa varieties suitable for cultivation in karst landscapes. These findings offer theoretical and practical insights for optimizing forage production in calcium-rich soils.

In response to the challenges posed by the low energy utilization of single-power pure electric vehicles and the limited lifespan of power batteries, this study focuses on the development of a compound power system. This study constructs a composite power system, analyzes the coupling characteristics of multiple systems, and investigates the energy management and optimal control mechanisms. Firstly, a power transmission scheme is designed for a hybrid electric vehicle. Then, a multi-state model is established to assess the electric vehicle’s performance under complex working conditions and explore how these conditions impact system coupling. Next, load power is redistributed using the Haar wavelet theory. The super capacitor is employed to stabilize chaotic and transient components in the required power, with low-frequency components serving as input variables for the controller. Further, power distribution is determined through the application of fuzzy logic theory. Input parameters include the system’s power requirements, power battery status, and super capacitor state of charge. The result is the output of a composite power supply distribution factor. To fully exploit the composite power supply’s potential and optimize the overall system performance, a global optimization control strategy using the dynamic programming algorithm is explored. The optimization objective is to minimize power loss within the composite power system, and the optimal control is calculated through interpolation using the interp function. Finally, a comparative simulation experiment is conducted under UDDS cycle conditions. The results show that the composite power system improved the battery discharge efficiency and reduced the number of discharge cycles and discharge current of the power battery. Under the cyclic working condition of 1369 s, the state of charge of the power battery in the hybrid power system decreases from 0.9 to 0.69, representing a 12.5% increase compared to the single power system. The peak current of the power battery in the hybrid power system decreases by approximately 20 A compared with that in the single power system. Based on dynamic programming optimization, the state of charge of the power battery decreases from 0.9 to 0.724. Compared with that of the single power system, the power consumption of the proposed system increases by 25%, that of the hybrid power fuzzy control system increases by 14.2%, and that of the vehicle decreases by 14.7% after dynamic programming optimization. The multimode energy shunt relationship is solved through efficient and reasonable energy management and optimization strategies. The performance and advantages of the composite energy storage system are fully utilized. This approach provides a new idea for the energy storage scheme of new energy vehicles.

Fine particulate matter (PM 2.5 ) and near-surface ozone (O 3 ) are the main atmospheric pollutants in China. Long-term exposure to high ozone concentrations adversely affects human health. It is of great significance to systematically analyze the spatiotemporal evolution mechanism and health effects of ozone pollution. Based on the ozone data of 91 monitoring stations in the Central Plains Urban Agglomeration from 2017 to 2020, the research used Kriging method and spatial autocorrelation analysis to investigate the spatiotemporal variations of ozone concentration. Additionally, the study assessed the health effects of ozone on the population using the population exposure risk model and exposure-response relationship model. The results indicated that: (1) The number of premature deaths caused by ozone pollution in the warm season were 37,053 at 95% confidence interval (95% CI: 28,190–45,930) in 2017, 37,685 (95% CI: 28,669–46,713) in 2018, and 37,655 (95% CI: 28,647–46,676) in 2019. (2) The ozone concentration of the Central Plains urban agglomeration showed a decreasing trend throughout the year and during the warm season from 2017 to 2020, there are two peaks monthly, one is June, and the other is September. (3) In the warm season, the high-risk areas of population exposure to ozone in the Central Plains Urban Agglomeration were mainly concentrated in urban areas. In general, the population exposure risk of the south is lower than that of the north. The number of premature deaths attributed to ozone concentration during the warm season has decreased, but some southern cities such as Xinyang and Zhumadian have also seen an increase in premature deaths. China has achieved significant results in air pollution control, but in areas with high ozone concentrations and high population density, the health burden caused by air pollution remains heavy, and stricter air pollution control policies need to be implemented.