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Digital infrastructure is increasingly regarded as a key enabler of economic modernization and urban sustainability, but its sustainability implications depend on whether digitalization guides innovation activities toward greener technological directions. Against the backdrop of China’s “dual carbon” goals and the deepening of low-carbon transformation, this study examines the relationship between digital infrastructure development and the green orientation of urban innovation from the perspective of innovation structure. Using panel data for 284 prefecture-level cities in China from 2011 to 2023, we measure the share of green innovation by the proportion of green invention patents in total granted patents, and use broadband Internet access users per 100 residents, denoted as InternetRate, as a proxy for digital infrastructure development. A two-way fixed effects model is employed to investigate the empirical relationship between the two. The results show that digital infrastructure development is significantly negatively associated with the relative share of green innovation within total innovation. This finding remains robust to alternative functional-form specifications, extreme-value treatment, alternative measures of digital infrastructure, and alternative measures of green innovation structure, and remains directionally consistent in a supplementary instrumental-variable test. Decomposition of scale effects indicates that this negative association reflects the relatively faster expansion of non-green innovation rather than an absolute contraction in green innovation, suggesting a structural reallocation pattern within urban innovation activities. Heterogeneity analysis shows that the negative association is mainly concentrated in cities with lower levels of economic development and higher text-based environmental governance attention, and is more pronounced in cities with a lower degree of industrial servitization. Moderation analysis further shows that this negative association becomes weaker in cities with stronger local green fiscal support. Spatial analysis indicates that the share of green innovation exhibits significant spatial dependence; however, the association between digital infrastructure development and innovation structure is mainly localized, with no significant spatial spillover detected. These findings contribute to sustainability research by showing that digital infrastructure does not automatically improve the green composition of innovation and that sustainable digital transformation requires complementary green fiscal support, environmental governance, and industrial upgrading policies.

Background Intrauterine growth restriction (IUGR) leads to cardiac dysfunction and adverse remodeling of the fetal heart, as well as a higher risk of postnatal cardiovascular diseases. The rat model of IUGR, via uterine artery ligation, is a popular model but its cardiac sequelae is not well investigated. Here, we performed an echocardiographic evaluation of its cardiac function to determine how well it can represent the disease in humans. Methods Unilateral uterine artery ligation was performed at embryonic day 17 (E17) and echocardiography was performed at E19 and E20. Results Growth-restricted fetuses were significantly smaller and lighter, and had an higher placenta-to-fetus weight ratio. Growth-restricted fetal hearts had reduced wall thickness-to-diameter ratio, indicating left ventricular (LV) dilatation, and they had elevated trans-mitral and trans-tricuspid E/A ratios and reduced left and right ventricular fractional shortening (FS), suggesting systolic and diastolic dysfunction. These were similar to human IUGR fetuses. However, growth-restricted rat fetuses did not demonstrate head-sparing effect, displayed a lower LV myocardial performance index, and ventricular outflow velocities were not significantly reduced, which were dissimilar to human IUGR fetuses. Conclusions Despite the differences, our results suggest that this IUGR model has significant cardiac dysfunction, and could be a suitable model for studying IUGR cardiovascular physiology. Impact Animal models of IUGR are useful, but their fetal cardiac function is not well studied, and it is unclear if they can represent human IUGR fetuses. We performed an echocardiographic assessment of the heart function of a fetal rat model of IUGR, created via maternal uterine artery ligation. Similar to humans, the model displayed LV dilatation, elevated E/A ratios, and reduced FS. Different from humans, the model displayed reduced MPI, and no significant outflow velocity reduction. Despite differences with humans, this rat model still displayed cardiac dysfunction and is suitable for studying IUGR cardiovascular physiology.

The naked mole rat (NMR), Heterocephalus glaber , is known as the longest-lived rodent and is extraordinarily resistant to hypoxia and cancer. Here, both NMR embryonic fibroblasts (NEFs) and their mouse counterparts (MEFs) were subjected to anoxic conditions (0% O 2 , 5% CO 2 ). A combination of comparative transcriptomics and proteomics was then employed to identify differentially expressed genes (DEGs). Notably, we observed distinct levels of histone H1.2 (encoded by HIST1H1C ) accumulation between NEFs and MEFs. Subsequent mechanistic analyses showed that higher H1.2 expression in NEFs was associated with the lower expression of its inhibitor, PARP1 . Additionally, we discovered that H1.2 can directly interact with HIF-1α PAS domains, thereby promoting the expression of HIF-1α through facilitating the dimerization with HIF-1β. The overexpression of H1.2 was also found to trigger autophagy and to suppress the migration of cancer cells, as well as the formation of xenograft tumors, via the NRF2/P62 signaling pathway. Moreover, an engineered H1.2 knock-in mouse model exhibited significantly extended survival in hypoxic conditions (4% O 2 ) and showed a reduced rate of tumor formation. Collectively, our results indicate a potential mechanistic link between H1.2 and the dual phenomena of anoxic adaptation and cancer resistance.

The two-component system “AfsQ1/Q2” plays a crucial role to activate the production of antibiotics ACT, RED, and CDA through directly binding the promoters of pathway-specific activator genes actII-ORF4, redZ, and cdaR respectively when grown under glutamate-supplemented minimal medium in Streptomyces coelicolor. In this report, we demonstrated that the RspA1/A2 (a homologous protein of two-component system AfsQ1/Q2) plays a regulatory role in salinomycin biosynthesis in Streptomyces albus. Gene deletion and complementation experiments showed that the RspA1/A2 promoted salinomycin production but inhibited cell growth when cultured in YMG medium supplemented with 3% soybean oil. More importantly, RspA1/A2 strengthens salinomycin biosynthesis by directly affecting the transcription of the pathway-specific activator gene slnR. Meanwhile, RspA1/A2 plays a negative role in the regulation of nitrogen assimilation and urea decarboxylation by interacting with the promoters of genes gdhA, glnA, amtB, and SLNWT_1828/1829. Gene sigW is located downstream of rspA1/A2 and encodes an extracytoplasmic function sigma factor. Moreover, it negatively regulates the salinomycin biosynthesis and promotes cell growth, which antagonizes the function of RspA1/A2. In short, these useful findings are proved helpful to enrich the understanding of the regulatory pathways of antibiotic biosynthesis by an ECF σ factor-TCS signal transduction system in Streptomyces.

Background Two gerbil species, sand rat (Psammomys obesus) and Mongolian jird (Meriones unguiculatus), can become obese and show signs of metabolic dysregulation when maintained on standard laboratory diets. The genetic basis of this phenotype is unknown. Recently, genome sequencing has uncovered very unusual regions of high guanine and cytosine (GC) content scattered across the sand rat genome, most likely generated by extreme and localized biased gene conversion. A key pancreatic transcription factor PDX1 is encoded by a gene in the most extreme GC-rich region, is remarkably divergent and exhibits altered biochemical properties. Here, we ask if gerbils have proteins in addition to PDX1 that are aberrantly divergent in amino acid sequence, whether they have also become divergent due to GC-biased nucleotide changes, and whether these proteins could plausibly be connected to metabolic dysfunction exhibited by gerbils. Results We analyzed ~ 10,000 proteins with 1-to-1 orthologues in human and rodents and identified 50 proteins that accumulated unusually high levels of amino acid change in the sand rat and 41 in Mongolian jird. We show that more than half of the aberrantly divergent proteins are associated with GC biased nucleotide change and many are in previously defined high GC regions. We highlight four aberrantly divergent gerbil proteins, PDX1, INSR, MEDAG and SPP1, that may plausibly be associated with dietary metabolism. Conclusions We show that through the course of gerbil evolution, many aberrantly divergent proteins have accumulated in the gerbil lineage, and GC-biased nucleotide substitution rather than positive selection is the likely cause of extreme divergence in more than half of these. Some proteins carry putatively deleterious changes that could be associated with metabolic and physiological phenotypes observed in some gerbil species. We propose that these animals provide a useful model to study the ‘tug-of-war’ between natural selection and the excessive accumulation of deleterious substitutions mutations through biased gene conversion.

Objective This study aims to systematically explore the effects of different physical exercises on balance ability in children with Down syndrome and to clarify the differences in the effects of various physical exercises on promoting the development of balance ability in children with Down syndrome. Methods The database search period was from July 1, 2024, to August 31, 2024. PubMed, Embase, Scopus, Web of Science, and Engineering Village databases were searched for all published studies involving randomized controlled trials from database establishment to August 31, 2024. The screening procedure complied with the stated inclusion and exclusion criteria and adhered strictly to the established inclusion and exclusion criteria. Using the Cochrane risk of bias assessment tool, the methodological quality of the chosen trials was determined. RevMan5.4.1 was used for data analysis, whereas Stata 16.0 was used to assess publication bias. Results This systematic review and meta-analysis incorporated eight randomized controlled trials comprising 260 participants. Meta-analysis showed that physical exercise significantly improved the dynamic balance (SMD = 1.45, 95%CI [1.14, 1.76], p  < 0.00001) and total balance (SMD = 1.44, 95%CI [1.04, 1.85], p  < 0.00001) in children with Down syndrome. Conclusion Physical exercise can improve balance in children with Down syndrome. Among the various exercise modalities, treadmill and core stability training appear to be among the more promising interventions, while Pilates and isokinetic training may also offer beneficial effects. Registration The study protocol has been duly registered with PROSPERO (CRD42024557710).

We consider a free boundary problem for the two-dimensional plasma-vacuum interface ideal magnetohydrodynamic (MHD) flows. In the plasma region, the flow is governed by the compressible ideal MHD equations, while in the vacuum region, we consider the full-Maxwell equations for the electric and the magnetic fields. At the free interface, driven by the plasma velocity, the total pressure is continuous and the magnetic field on both sides is tangent to the boundary. We establish a linear stability/instability criterion of equilibrium state for the Rayleigh-Taylor (RT) problem and the linear stability for the ideal MHD equations. More specifically, we study the stabilizing effect of impressed magnetic fields upon solutions to the equations obtained by linearization around the equilibrium state. We give the critical magnetic number H c by a modified variational method and prove that the linearized system is stable when the horizontal impressed magnetic field H ¯ = ( H ¯ 1 , 0 ) satisfies | H ¯ 1 | > H c , while unstable for | H ¯ 1 | < H c .

Human umbilical cord mesenchymal stem/stromal cells (hUC-MSCs) have attracted significant research interests in regenerative medicine and cell-based therapies due to their minimally invasive isolation procedure, abundant availability, allogenic nature, improved proliferation capacity and tri-lineage differentiation potential. However, the challenge in harvesting a sufficient number of hUC-MSCs through conventional static culture for downstream application hinders the downstream clinical translation of hUC-MSCs. Hence, an alternative culture method that can facilitate large-scale expansion is highly desirable. Herein, we developed a microcarrier-based dynamic culture system to culture hUC-MSCs combined fed-batch mode with medium refreshment to decrease concentrations of metabolic wastes, improve nutrient supplement and reduce the amount of medium used for cell culture. Instead of refreshing medium based on the pre-determined frequency, the replacement and feeding of medium using the novel feeding regime were carried out based on consumption of nutrients (glucose and glutamine) and production of metabolic waste (lactate and ammonia) to maintain a balanced and benign culture microenvironment. The optimal process allowed over 20 folds increase of cell with a maximum cell density at (24.13 ± 0.59) × 10 5 cells/mL. In addition, no significant alteration of cell surface markers of hUC-MSCs derived from dynamic conditions was observed compared to static conditions. Impressively, over 99.8% of the cellular population showed the desired positive expression of CD73, CD90 and CD105, while less than 0.2% of the population showed undesired negative expression of CD34, CD45 and HLA-DR. More importantly, hUC-MSCs derived from our dynamic culture condition still maintained their trilineage differentiation capacity.