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Background: To determine the carrier frequency of, and evaluate a carrier screening program for, spinal muscular atrophy (SMA) in reproductive age women in Shenzhen area. Methods: A staged screening procedure was used to perform carrier screening for SMA in 22,913 Chinese reproductive age women between 2019 and 2022 in Shenzhen area of China. First, the copy number of exon 7 in the SMN1 gene were detected in women of reproductive age using real‐time quantitative polymerase chain reaction. If SMA carriers were detected, their spouses were then recommended to test. Prenatal diagnosis was carried out in couples who were both carriers. Results: A total of 389 women were found to be SMA carriers (1.70%, 95% CI: 1.53%–1.87%), indicating the carrier prevalence was approximately 1:59. Despite the proportion of nonpregnant women increased from 37.96% in 2019 to 58.18% in 2022 (p < 0.05) among the 22,913 reproductive age women, the recall rate of spouses was still not high (62.21%, 95% CI: 57.39%–67.03%). Eight partners were found to be SMA carriers and two fetuses were determined to have SMA with no copies of the SMN1 gene. Conclusion: Although the acceptability and awareness of SMA carrier screening in Chinese population has increased in recent years, it still fails to reach the ideal expectation. Our experience may provide a basis for and facilitate the popularization of SMA carrier screening in Shenzhen area. [ABSTRACT FROM AUTHOR]

A novel matrix converter‐based topology to be applied in smart transformers (STs) is proposed, based on the concept of multiple modularity. To replace the conventional ST topology obtained by H‐bridge modules including DC electrolytic capacitors, the proposed ST topology uses two kinds of matrix modules to provide flexibility in the AC–AC structures to build complex ST. Fewer power semiconductor devices are used in each module to reduce the costs. The AC–AC matrix converters and the high‐frequency transformers eliminate electrolytic capacitors, enhancing ST reliability and power density. The modulation method for the proposed ST structure needs suited carrier waves and switching processes. The half‐Venturini modulation method shows several switching sequences leading to voltage imbalances in the input film capacitor divider. Therefore, the paper investigates and analyses the influence of switching sequences on the capacitor voltages in detail. The results show that the different switching sequences will cause different currents flowing into capacitors, leading to different results in capacitor voltages. Based on the analysis, proper modulations are recommended for the proposed topology. In order to verify the feasibility of the proposed topology as well as the correctness of the analysis on modulations, simulations and hardware‐in‐loop experiments are carried out. It is found that the modularity concept is feasible, and a suitable modulation sequence was developed to balance the input capacitors voltages. [ABSTRACT FROM AUTHOR]

Reaumuria songarica, a drought‐resistant shrub, is widely distributed and plays a crucial role in the northern deserts of China. It is a key species for desert rehabilitation and afforestation efforts. Using the Maxent model to predict suitable planting areas for R. songarica is an important strategy for combating desertification. With 184 occurrence points of R. songarica and 13 environmental variables, the optimized Maxent model has identified the main limiting factors for its distribution. Distribution patterns and variation trends of R. songarica were projected for current and future climates (2030s, 2050s, 2070s, and 2090s) and different scenarios (ssp_126, ssp_370, and ssp_585). Results show that setting parameters to RM (regulation multiplier) = 4 and FC (feature combination) = LQHPT yields a model with good accuracy and high reliability. Currently, R. songarica is primarily suitable for desert control in eight provinces and autonomous regions, including Inner Mongolia, Xinjiang, Qinghai, and Ningxia. The total suitable planting area is 148.80 × 104 km2, representing 15.45% of China's land area. Precipitation (Precipitation of the wettest month, Precipitation of the warmest quarter, and Annual precipitation) and Ultraviolet‐B seasonality are the primary environmental factors limiting the growth and distribution of R. songarica. Mean temperature of the warmest quarter is the primary factor driving changes in the distribution of suitable areas for R. songarica under future climate scenarios. In future climate scenarios, the suitable planting area of R. songarica will shrink, and the distribution center will shift towards higher latitude, potentially indicate further desertification. The area of highly suitable habitat has increased, while moderately and less suitable habitat areas have decreased. Increased precipitation within R. songarica's water tolerance range is favorable for its growth and reproduction. With changes in the suitable cultivation area for R. songarica, priority should be given to exploring and utilizing its germplasm resources. Introduction and cultivation can be conducted in expanding regions, while scientifically effective measures should be implemented to protect germplasm resources in contracting regions. The findings of this study provide a theoretical basis for addressing desertification resulting from climate change and offer practical insights for the development, utilization, introduction, and cultivation of R. songarica germplasm resources. [ABSTRACT FROM AUTHOR]

The binding of peroxisome proliferator‐activated receptor γ (PPARγ) to the orphan nuclear receptor Nur77 facilitates the ubiquitination and degradation of Nur77, and leads to aberrant fatty acid uptake for breast cancer progression. Because of its crucial role in clinical prognosis, the interaction between Nur77 and PPARγ is an attractive target for anti‐breast‐cancer therapy. However, developing an inhibitor of the Nur77‐PPARγ interaction poses a technical challenge due to the absence of the crystal structure of PPARγ and its corresponding interactive model with Nur77. Here, ST‐CY14, a stapled peptide, is identified as a potent modulator of Nur77 with a KD value of 3.247 × 10−8 M by in silico analysis, rational design, and structural modification. ST‐CY14 effectively increases Nur77 protein levels by blocking the Nur77‐PPARγ interaction, thereby inhibiting lipid metabolism in breast tumor cells. Notably, ST‐CY14 significantly suppresses breast cancer growth and bone metastasis in mice. The findings demonstrate the feasibility of exploiting directly Nur77‐PPARγ interaction in breast cancer, and generate what to the best knowledge is the first direct inhibitor of the Nur77‐PPARγ interaction available for impeding fatty acid uptake and therapeutic development. [ABSTRACT FROM AUTHOR]

DNA methylation alterations play mechanistic roles in aging; however, the epigenetic regulators/mediators causally involved in renal aging remain elusive. Here, we report that natural and D‐galactose (D‐gal)‐induced aging kidneys display marked suppression of antiaging factor NRF2 (nuclear factor erythroid‐derived 2‐like 2) and KLOTHO, accompanied by upregulations of DNA methyltransferase (DNMT) 1/3a/3b and NRF2/KLOTHO gene promoter hypermethylations. Administration of a DNMT inhibitor SGI‐1072 effectively hypomethylated the promoters, derepressed NRF2/KLOTHO, and mitigated the structural and functional alterations of renal aging in D‐gal mice. Moreover, oleuropein (OLP), an olive‐derived polyphenol, also displayed similar epigenetic modulation and antiaging effects. OLP inhibited the epigenetic NRF2/KLOTHO suppressions in a gain of DNMT‐sensitive manner in cultured renal cells, demonstrating a strong DNA‐demethylating capacity. In NRF2 knockout and KLOTHO knockdown D‐gal mice, OLP exhibited reduced antiaging effects with KLOTHO displaying a prominent gene effect and effect size; consistently in KLOTHO knockdown mice, the antiaging effects of SGI‐1027 were largely abrogated. Therefore, the KLOTHO recovery is critical for the antiaging effects of DNA demethylation. Collectively, our data indicate that aberrant DNMT1/3a/3b elevations and the resultant suppression of antiaging factors contribute significantly to epigenetic renal aging, which might be targeted for epigenetic intervention by synthetic or natural DNA‐demethylating agents. [ABSTRACT FROM AUTHOR]

Aims: The aim was to investigate the effect of mood disorders on parkinsonian toxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced motor disability, substantia nigra pars compacta (SNc) dopaminergic (DA) neurons loss. Also, the neural circuit mechanism was elucidated. Methods: The depression‐like (physical stress, PS) and anxiety‐like (emotional stress, ES) mouse models were established by the three‐chamber social defeat stress (SDS). The features of Parkinson's disease were reproduced by MPTP injection. Viral‐based whole‐brain mapping was utilized to resolve the stress‐induced global changes in direct inputs onto SNc DA neurons. Calcium imaging and chemogenetic techniques were applied to verify the function of the related neural pathway. Results: We found that PS mice, but not ES mice, showed worse movement performance and more SNc DA neuronal loss than control mice after MPTP administration. The projection from the central amygdala (CeA) to the SNcDA was significantly increased in PS mice. The activity of SNc‐projected CeA neurons was enhanced in PS mice. Activating or inhibiting the CeA‐SNcDA pathway could mimic or block PS‐induced vulnerability to MPTP. Conclusions: These results indicated that projections from CeA to SNc DA neurons contribute to SDS‐induced vulnerability to MPTP in mice. [ABSTRACT FROM AUTHOR]

Caveolae are intracellular vesicles with diameters ranging from 50 to 100 nm. The role of caveolins in mediating oxidative stress, autophagy, apoptosis, fibrosis, and vascular remodeling has attracted increasing attention in cardiovascular therapy. Several studies have suggested that caveolin could be a therapeutic target for the treatment of cardiac and/or vascular injury via several pathophysiological mechanisms. Despite substantial advances in our understanding of the basic biology of vesicles over the past decade, the relevance and specific role of these mechanisms in cardiovascular homeostasis remains ambiguous. Here, we review the macroscopic role of caveolins in protecting cardiac function and, at the microscopic level, examine possible cardioprotective caveolar mechanisms, including their antioxidative stress, antiapoptosis, autophagy‐regulatory, antifibrosis, and angiogenesis‐promoting properties. We believe that the role of caveolins in cardiac functioning has not been fully elucidated and is an important line of future research with several cardioprotective implications. [ABSTRACT FROM AUTHOR]

Effective modification of the structure and properties of halide perovskites via the pressure engineering strategy has attracted enormous interest in the past decade. However, sufficient effort and insights regarding the potential properties and applications of the high‐pressure amorphous phase are still lacking. Here, the superior and tunable photoelectric properties that occur in the pressure‐induced amorphization process of the halide perovskite Cs3Bi2I9 are demonstrated. With increasing pressure, the photocurrent with xenon lamp illumination exhibits a rapid increase and achieves an almost five orders of magnitude increment compared to its initial value. Impressively, a broadband photoresponse from 520 to 1650 nm with an optimal responsivity of 6.81 mA W−1 and fast response times of 95/96 ms at 1650 nm is achieved upon successive compression. The high‐gain, fast, broadband, and dramatically enhanced photoresponse properties of Cs3Bi2I9 are the result of comprehensive photoconductive and photothermoelectric mechanisms, which are associated with enhanced orbital coupling caused by an increase in BiI interactions in the [BiI6]3− cluster, even in the amorphous state. These findings provide new insights for further exploring the potential properties and applications of amorphous perovskites. [ABSTRACT FROM AUTHOR]

Background and Purpose: Development of pulmonary fibrosis is associated with altered DNA methylation modifications of fibrogenic gene expression. However, their causal relationships and the underlying mechanisms remain unclear. This study investigates the critical role of DNA methylation aberration‐associated suppression of peroxisome proliferator‐activated receptor‐γ (PPARγ) in pulmonary fibrosis. Experimental Approach Expression of PPARγ and bioactive DNA methyltransferases (DNMTs) and PPARγ promoter methylation status were examined in fibrotic lungs of idiopathic pulmonary fibrosis (IPF) patients and bleomycin (Blm)‐treated mice. DNA demethylating agent 5‐aza‐2′‐deoxycytidine (5aza) and glycyrrhizic acid (GA) derived from medicinal plant were assessed for their PPARγ de‐repression and anti‐pulmonary fibrosis activities. PPARγ knockout mice were created to determine the critical role of PPARγ in this protection. Key Results: Lung PPARγ expression was markedly suppressed in IPF patients and Blm mice, accompanied by increased DNMT 1/DNMT3a and PPARγ promoter hypermethylation. Administration of 5‐aza and GA similarly demethylated PPARγ promoter, restored PPARγ loss and alleviated fibrotic lung pathologies, including structural alterations and adverse expression of fibrotic mediators and inflammatory cytokines. In cultured lung fibroblasts and alveolar epithelial cells, GA alleviated PPARγ–mediated suppression of fibrosis in a gain of DNMT‐sensitive manner, and in PPARγ knockout mice, the anti‐fibrotic effects of 5aza and GA were significantly reduced, suggesting that PPARγ is a critical mediator of epigenetic pulmonary fibrogenesis. Conclusion and Implications: Aberrant DNMT1/3a elevations and the resultant PPARγ suppression contribute significantly to the development of pulmonary fibrosis, and strategies targeting DNMT/PPARγ axis with synthetic or natural compounds might benefit patients with pulmonary fibrotic disorders. [ABSTRACT FROM AUTHOR]

There has been increasing concern that the overuse of antibiotics in livestock farming is contributing to the burden of antimicrobial resistance in people. Farmed animals in Europe and North America, particularly pigs, provide a reservoir for livestock‐associated methicillin‐resistant Staphylococcus aureus (LA‐MRSA ST398 lineage) found in people. This study is designed to investigate the contribution of MRSA from Chinese pig farms to human infection. A collection of 483 MRSA are isolated from 55 farms and 4 hospitals in central China, a high pig farming density area. CC9 MRSA accounts for 97.2% of all farm isolates, but is not present in hospital isolates. ST398 isolates are found on farms and hospitals, but none of them formed part of the "LA‐MRSA ST398 lineage" present in Europe and North America. The hospital ST398 MRSA isolate form a clade that is clearly separate from the farm ST398 isolates. Despite the presence of high levels of MRSA found on Chinese pig farms, the authors find no evidence of them spilling over to the human population. Nevertheless, the ST398 MRSA obtained from hospitals appear to be part of a widely distributed lineage in China. The new animal‐adapted ST398 lineage that has emerged in China is of concern. [ABSTRACT FROM AUTHOR]

There has been increasing concern that the overuse of antibiotics in livestock farming is contributing to the burden of antimicrobial resistance in people. Farmed animals in Europe and North America, particularly pigs, provide a reservoir for livestock‐associated methicillin‐resistant Staphylococcus aureus (LA‐MRSA ST398 lineage) found in people. This study is designed to investigate the contribution of MRSA from Chinese pig farms to human infection. A collection of 483 MRSA are isolated from 55 farms and 4 hospitals in central China, a high pig farming density area. CC9 MRSA accounts for 97.2% of all farm isolates, but is not present in hospital isolates. ST398 isolates are found on farms and hospitals, but none of them formed part of the "LA‐MRSA ST398 lineage" present in Europe and North America. The hospital ST398 MRSA isolate form a clade that is clearly separate from the farm ST398 isolates. Despite the presence of high levels of MRSA found on Chinese pig farms, the authors find no evidence of them spilling over to the human population. Nevertheless, the ST398 MRSA obtained from hospitals appear to be part of a widely distributed lineage in China. The new animal‐adapted ST398 lineage that has emerged in China is of concern. [ABSTRACT FROM AUTHOR]

There has been increasing concern that the overuse of antibiotics in livestock farming is contributing to the burden of antimicrobial resistance in people. Farmed animals in Europe and North America, particularly pigs, provide a reservoir for livestock‐associated methicillin‐resistant Staphylococcus aureus (LA‐MRSA ST398 lineage) found in people. This study is designed to investigate the contribution of MRSA from Chinese pig farms to human infection. A collection of 483 MRSA are isolated from 55 farms and 4 hospitals in central China, a high pig farming density area. CC9 MRSA accounts for 97.2% of all farm isolates, but is not present in hospital isolates. ST398 isolates are found on farms and hospitals, but none of them formed part of the "LA‐MRSA ST398 lineage" present in Europe and North America. The hospital ST398 MRSA isolate form a clade that is clearly separate from the farm ST398 isolates. Despite the presence of high levels of MRSA found on Chinese pig farms, the authors find no evidence of them spilling over to the human population. Nevertheless, the ST398 MRSA obtained from hospitals appear to be part of a widely distributed lineage in China. The new animal‐adapted ST398 lineage that has emerged in China is of concern. [ABSTRACT FROM AUTHOR]

Objectives: Evidences demonstrate that sorafenib alleviates liver fibrosis via inhibiting HSC activation and ECM accumulation. The underlying mechanism remains unclear. Ferroptosis, a novel programmed cell death, regulates diverse physiological/pathological processes. In this study, we aim to investigate the functional role of HSC ferroptosis in the anti‐fibrotic effect of sorafenib. Materials and Methods: The effects of sorafenib on HSC ferroptosis and ECM expression were assessed in mouse model of liver fibrosis induced by CCl4. In vitro, Fer‐1 and DFO were used to block ferroptosis and then explored the anti‐fibrotic effect of sorafenib by detecting α‐SMA, COL1α1 and fibronectin proteins. Finally, HIF‐1α siRNA, plasmid and stabilizers were applied to assess related signalling pathway. Results: Sorafenib attenuated liver injury and ECM accumulation in CCl4‐induced fibrotic livers, accompanied by reduction of SLC7A11 and GPX4 proteins. In sorafenib‐treated HSC‐T6 cells, ferroptotic events (depletion of SLC7A11, GPX4 and GSH; accumulation iron, ROS and MDA) were discovered. Intriguingly, these ferroptotic events were not appeared in hepatocytes or macrophages. Sorafenib‐elicited HSC ferroptosis and ECM reduction were abrogated by Fer‐1 and DFO. Additionally, both HIF‐1α and SLC7A11 proteins were reduced in sorafenib‐treated HSC‐T6 cells. SLC7A11 was positively regulated by HIF‐1α, inactivation of HIF‐1α/SLC7A11 pathway was required for sorafenib‐induced HSC ferroptosis, and elevation of HIF‐1α could inhibit ferroptosis, ultimately limited the anti‐fibrotic effect. Conclusions: Sorafenib triggers HSC ferroptosis via HIF‐1α/SLC7A11 signalling, which in turn attenuates liver injury and fibrosis. [ABSTRACT FROM AUTHOR]

The Hippo pathway effector TAZ promotes cellular growth, survival, and stemness through regulating gene transcription. Recent studies suggest that TAZ liquid–liquid phase separation (LLPS) compartmentalizes key cofactors to activate transcription. However, how TAZ LLPS is achieved remains unknown. Here, it is shown that the paraspeckle protein NONO is required for TAZ LLPS and activation in the nucleus. NONO is a TAZ‐binding protein. Their interaction shows temporal regulation parallel to the interaction between TAZ and TEAD as well as to the expression of TAZ target genes. NONO depletion reduces nuclear TAZ LLPS, while ectopic NONO expression promotes the LLPS. Accordingly, NONO depletion reduces TAZ interactions with TEAD, Rpb1, and enhancers. In glioblastoma, expressions of NONO and TAZ are both upregulated and predict poor prognosis. Silencing NONO expression in an orthotopic glioblastoma mouse model inhibits TAZ‐driven tumorigenesis. Together, this study suggests that NONO is a nuclear factor that promotes TAZ LLPS and TAZ‐driven oncogenic transcriptional program. [ABSTRACT FROM AUTHOR]