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In August 2022, East China experienced an unprecedented heatwave, characterized by strengthened Western Pacific subtropical high and an extreme flash drought in the Yangtze River Basin. The extreme compound dry and hot event could be amplified by local land–atmosphere interactions, with increased sensible heat raising temperature and prohibiting precipitation. However, whether the upwind antecedent flash drought exacerbated the downwind East China heatwave through the remote land–atmosphere interaction remains elusive. In this study, we used Lagrangian heat tracking analysis and the Weather Research and Forecasting Model (WRF) simulations to quantify the impact of upwind soil moisture anomaly on atmospheric circulation and downwind record-shattering heatwave. We found that there were heatwaves in both July and August of 2022 over East China, but their underlying mechanisms were different. The subtropical high in August was stronger than the July heatwave, and only the August heatwave was affected by upwind flash drought. This heatwave lasted for 22 days, which set a historical record of duration since 1961. Besides the subtropical high, the upwind flash drought played a key role in amplifying this heatwave. Specifically, the upwind flash drought enhanced surface sensible heating, and strengthened diabatic heating of the atmosphere. This led to a 54.7% increase of the advected sensible heat transported to East China, and maintained the anticyclone anomaly. If there was no soil moisture drought in the upwind region, the maximum temperature would decrease by 0.34 °C-1.34 °C. This suggests that upwind flash drought may emerge as one of the key factors for downwind record-shattering heatwaves.

Hypoxia is a major regulator of tumor aggressiveness and metastasis in cancer progression. Exosomes (exos) play an important role in the communication between lung cancer and hypoxic microenvironment. However, the underlying mechanisms are largely undefined. Exos were isolated from A549 cells under hypoxia conditions. Transmission electron microscopy and nanoparticle tracking analysis were carried out to characterize exos. CCK-8 assay, flow cytometry, Western blot, wound healing, and transwell assays were performed to assess the proliferation, apoptosis, migration, and invasion of A549 cells, respectively. The M2 polarization of macrophages was evaluated by RT-qPCR and Western blot analysis. In vivo nude mice model was established to determine the regulatory effect of hypoxia/exos on the progression of lung cancer. Hypoxic A549 cell-derived exos (hypoxia/exos) promoted the proliferation and migration, and inhibited the apoptosis in A549 cells. The expression of PKM2 was significantly upregulated in hypoxia/exos. Hypoxic exosomal PKM2 induced M2 polarization of macrophages by activating AMPK pathway. Co-culture with hypoxia/exos-treated macrophages enhanced the migration, invasion, and epithelial-mesenchymal transition (EMT) in A549 cells. Moreover, treatment with hypoxia/exos facilitated the tumor growth and lung metastasis of A549 cells. Our findings reveal that hypoxic exosomal PKM2 induces M2 macrophage polarization via AMPK pathway, and thus exerts a simulative effect on the growth and metastasis of lung carcinoma.

Bismuth ferrite (BiFeO 3 ) is a multiferroic material that exhibits both ferroelectricity and canted antiferromagnetism at room temperature, making it a unique candidate in the development of electric-field controllable magnetic devices. The magnetic moments in BiFeO 3 are arranged into a spin cycloid, resulting in unique magnetic properties which are tied to the ferroelectric order. Previous understanding of this coupling has relied on average, mesoscale measurements. Using nitrogen vacancy-based diamond magnetometry, we observe the magnetic spin cycloid structure of BiFeO 3 in real space. This structure is magnetoelectrically coupled through symmetry to the ferroelectric polarization and this relationship is maintained through electric field switching. Through a combination of in-plane and out-of-plane electrical switching, coupled with ab initio studies, we have discovered that the epitaxy from the substrate imposes a magnetoelastic anisotropy on the spin cycloid, which establishes preferred cycloid propagation directions. The energy landscape of the cycloid is shaped by both the ferroelectric degree of freedom and strain-induced anisotropy, restricting the spin spiral propagation vector to changes to specific switching events. Previous understanding of the coupling between ferroelectric structure and magnetic texture in BiFeO 3 has relied on mesoscale measurements. Here, the authors image coupling directly, showing a complex spin cycloid controlled with electric field.

Magnetic skyrmions are of great interest to both fundamental research and applications in post-von-Neumann computing devices. The successful implementation of skyrmionic devices requires functionalities of skyrmions with effective controls. Here we show that the local dynamics of skyrmions, in contrast to the global dynamics of a skyrmion as a whole, can be introduced to provide effective functionalities for versatile computing. A single skyrmion interacting with local pinning centres under thermal effects can fluctuate in time and switch between a small-skyrmion and a large-skyrmion state, thereby serving as a robust true random number generator for probabilistic computing. Moreover, neighbouring skyrmions exhibit an anti-correlated coupling in their fluctuation dynamics. Both the switching probability and the dynamic coupling strength can be tuned by modifying the applied magnetic field and spin current. Our results could lead to progress in developing magnetic skyrmionic devices with high tunability and efficient controls. Skyrmions, a kind of topological spin texture, have been considered as having potential for use in spin-based computing. Here, Wang et al. study the local dynamics of skyrmions interacting with pinning sites, demonstrating a skyrmion true random number generator with the magnetic field and spin current as two control parameters.

Flash droughts challenge early warnings due to their rapid onset, which requires a proper drought index and skillful nowcasting system. A few studies have assessed the nowcast skill for flash droughts using a one-dimensional index, but whether the models can capture their spatiotemporal evolution remains unclear. In this study, a three-dimensional meteorological flash drought index based on the percentile of 15-day moving average precipitation minus evapotranspiration (P-ET) is developed. The index is then used to investigate the spatiotemporal evolution of a mega-flash drought that occurred in the Yangtze River basin during the summer of 2022. The results show that the mega-flash drought started at the beginning of July in the upper reaches of the river and expanded to the middle and lower reaches at the beginning of August due to the spread of the high-pressure system. The evolution is well captured by the proposed three-dimensional index. The spatial correlations between the China Meteorological Administration global medium-range ensemble forecast system (CMA-GFS)’s nowcast and reanalysis ranged from 0.58 to 0.85, and the hit rate and equitable threat score are 0.54 and 0.26, respectively. This study shows that the CMA-GFS nowcast of the P-ET index roughly captured the drought’s evolution, which can be used for flash drought early warnings and water resource management.

Background As a hot method in machine learning field, the forests approach is an attractive alternative approach to Cox model. Random survival forests (RSF) methodology is the most popular survival forests method, whereas its drawbacks exist such as a selection bias towards covariates with many possible split points. Conditional inference forests (CIF) methodology is known to reduce the selection bias via a two-step split procedure implementing hypothesis tests as it separates the variable selection and splitting, but its computation costs too much time. Random forests with maximally selected rank statistics (MSR-RF) methodology proposed recently seems to be a great improvement on RSF and CIF. Methods In this paper we used simulation study and real data application to compare prediction performances and variable selection performances among three survival forests methods, including RSF, CIF and MSR-RF. To evaluate the performance of variable selection, we combined all simulations to calculate the frequency of ranking top of the variable importance measures of the correct variables, where higher frequency means better selection ability. We used Integrated Brier Score ( IBS ) and c-index to measure the prediction accuracy of all three methods. The smaller IBS value, the greater the prediction. Results Simulations show that three forests methods differ slightly in prediction performance. MSR-RF and RSF might perform better than CIF when there are only continuous or binary variables in the datasets. For variable selection performance, When there are multiple categorical variables in the datasets, the selection frequency of RSF seems to be lowest in most cases. MSR-RF and CIF have higher selection rates, and CIF perform well especially with the interaction term. The fact that correlation degree of the variables has little effect on the selection frequency indicates that three forest methods can handle data with correlation. When there are only continuous variables in the datasets, MSR-RF perform better. When there are only binary variables in the datasets, RSF and MSR-RF have more advantages than CIF. When the variable dimension increases, MSR-RF and RSF seem to be more robustthan CIF Conclusions All three methods show advantages in prediction performances and variable selection performances under different situations. The recent proposed methodology MSR-RF possess practical value and is well worth popularizing. It is important to identify the appropriate method in real use according to the research aim and the nature of covariates.

Metabolic syndrome (MS) is an increasing public health concern because of rapid lifestyle changes. Although there have been previous studies on the prevalence of MS in China, the prevalence may have changed with lifestyle changes over the last decade. To update this prevalence, we performed a cross-sectional survey among adults over 18 years old across China from May 2013 to July 2014. Participants underwent questionnaires and provided blood and urine samples for analysis. MS was defined according to the criteria of the China Diabetes Society. A total of 12570 individuals (45.2% men) with an average age of 48.8±15.3 (18-96) years were selected and invited to participate in the study. In total, 9310 (40.7% men) individuals completed the investigation, with a response rate of 74.1%. The prevalence of MS in China was 14.39% [95% confidence interval (CI): -3.75-32.53%], and the age-adjusted prevalence was 9.82% (95% CI: 9.03-10.61%; 7.78% in men and 6.76% in women; 7.39% in rural residents and 6.98% in urban residents). The highest prevalence occurred among adults aged 50-59 years (1.95%, 95% CI: 1.40-2.50%), and the lowest prevalence occurred among adults aged 40-49 years (0.74%, 95% CI: 0.38-1.10%); the prevalence was the highest in the south region and lowest in the east region (4.46% and 1.23%, respectively). The results of logistic regression analyses showed that age, urolithiasis, hyperuricemia, coronary artery disease, thiazide drugs intake, family history of diabetes and hypertension were all significantly associated with an increased risk of metabolic syndrome (OR>1). In addition, education, vitamin D intake and family history of urolithiasis are all protective factors (OR<1). Our results indicate that there was a high prevalence of MS in Chinese adults. Compared to the previous study 10 years ago, some preventive strategies have worked; however, further work on the prevention and treatment of MS remains necessary.

Lung cancer is the leading cause of cancer-related deaths worldwide. Tumor suppressor genes remain to be systemically identified for lung cancer. Through the genome-wide screening of tumor-suppressive transcription factors, we demonstrate here that GATA4 functions as an essential tumor suppressor in lung cancer in vitro and in vivo. Ectopic GATA4 expression results in lung cancer cell senescence. Mechanistically, GATA4 upregulates multiple miRNAs targeting TGFB2 mRNA and causes ensuing WNT7B downregulation and eventually triggers cell senescence. Decreased GATA4 level in clinical specimens negatively correlates with WNT7B or TGF-β2 level and is significantly associated with poor prognosis. TGFBR1 inhibitors show synergy with existing therapeutics in treating GATA4-deficient lung cancers in genetically engineered mouse model as well as patient-derived xenograft (PDX) mouse models. Collectively, our work demonstrates that GATA4 functions as a tumor suppressor in lung cancer and targeting the TGF-β signaling provides a potential way for the treatment of GATA4-deficient lung cancer. The tumor suppressor GATA4 is frequently epigenetically silenced in lung cancer. In this study, Gao et al. demonstrate that GATA4 regulates the expression of TGFBR2 and that TGFRB1 inhibitors can synergise with chemotherapeutics to inhibit the growth of GATA4-deficient tumors in mice.

The development of dielectric ceramics that simultaneously achieve high energy density and ultra-broad temperature stability remains a fundamental challenge for advanced electrostatic capacitors. Here, we report a high-entropy engineering strategy that transforms conventional relaxor ferroelectric BT-Bi(Mg 0.5 Zr 0.5 )O 3 into entropy-stabilized BT-H through a dual-phase cationic disorder modulation. By maximizing configurational entropy, this approach induces atomic-scale lattice heterogeneity with reduced size of polar units, and establishes temperature-adaptive multiphase coexistence structure, effectively decoupling polarization configuration from thermal fluctuations. Consequently, the optimized BT-H ceramics exhibit extraordinary recoverable energy density (W rec ) of 8.9 J cm -3 , near ideal conversion efficiency (η) of ~ 97.8 % and superior temperature stability of ΔW rec ~±9 % and Δη ~ ±4.8% over a ultrawide operational range (−85-220 °C). This work validates the entropy-mediated cocktail effect, demonstrating that leveraging high-entropy materials to design capacitors with superior integrated energy storage performance is an advanced and viable strategy. The authors achieve high energy storage performance with near-ideal energy conversion efficiency and outstanding temperature stability in the entropy-stabilized ferroelectric ceramics by constructing a temperature-adaptive multiphase coexistence structure.

Background Reprogrammed energy metabolism as an emerging hallmark of cancer has recently drawn special attention since it facilitate cell growth and proliferation. Recently, long noncoding RNAs (lncRNAs) have been served as key regulators implicated in tumor development and progression by promoting proliferation, invasion and metastasis. However, the associations of lncRNAs with cellular energy metabolism in lung cancer (LC) need to be clarified. Methods Here, we conducted bioinformatics analysis and found insulin-like growth factor binding protein 4–1 (IGFBP4–1) as a new candidate lncRNA located in the upstream region of IGFBP4 gene. The expression levels of lnc-IGFBP4–1, mRNA levels of IGFBP4 in 159 paired lung cancer samples and adjacent, histological normal tissues by qRT-PCR. Over-expression and RNA interference (RNAi) approaches were adopted to investigate the biological functions of lnc-IGFBP4–1. The intracellular ATP level was measured using the Cell Titer-Glo Luminescent Cell Viability Assay kit, and changes in metabolic enzymes were examined in cancer cells and normal pulmonary epithelial cells with qRT-PCR. Results Our results showed that lnc-IGFBP4–1 was significantly up-regulated in LC tissues compared with corresponding non-tumor tissues ( P  < 0.01), and its expression level was significantly correlated with TNM stage ( P  < 0.01) and lymph node metastasis ( P  < 0.05). Further investigation showed that overexpression of lnc-IGFBP4–1 significantly promoted LC cell proliferation in vitro and in vivo, while downregulation of endogenous lnc-IGFBP4–1 could inhibited cell proliferation and induce apoptosis. Moreover, we found lnc-IGFBP4–1 could influences ATP production levels and expression of enzymes including HK2, PDK1 and LDHA, in addition, decline in both ATP production and these enzymes in response to 2-DG and 2-DG-combined Rho123, respectively, was observed in lnc-IGFBP4–1-overespressing LC cells, indicative of an enhanced aerobic glycolysis rate. Finally, lnc-IGFBP4–1 was observed to negatively correlate with gene IGFBP4, and lower expression level of IGFPB4 was found after lnc-IGFBP4–1-overexpression was transfected into PC9 cells, higher expression level of IGFPB4 was also found after lnc-IGFBP4–1-downregulation was transfected into GLC-82 cells, which indicates that IGFBP4 may exert its targeting function regulated by lnc-IGFBP4–1. Conclusions Taken together, these findings provide the first evidence that lnc-IGFBP4–1 is significantly up-regulated in LC tissues and plays a positive role in cell proliferation and metastasis through possible mechanism of reprogramming tumor cell energy metabolism, which suggests that lnc-IGFBP4–1 may be a promising biomarker in LC development and progression and as a potential therapeutic target for LC intervention.