Molecular orbital breaking in photo-mediated organosilicon Schiff base ferroelectric crystals.

Ferroelectric materials, whose electrical polarization can be switched under external stimuli, have been widely used in sensors, data storage, and energy conversion. Molecular orbital breaking can result in switchable structural and physical bistability in ferroelectric materials as traditional spatial symmetry breaking does. Differently, molecular orbital breaking interprets the phase transition mechanism from the perspective of electronics and sheds new light on manipulating the physical properties of ferroelectrics. Here, we synthesize a pair of organosilicon Schiff base ferroelectric crystals, (R)- and (S)-N-(3,5-di-tert-butylbenzylidene)-1-((triphenylsilyl)oxy)ethanamine, which show optically controlled phase transition accompanying the molecular orbital breaking. The molecular orbital breaking is manifested as the breaking and reformation of covalent bonds during the phase transition process, that is, the conversion between C = N and C-O in the enol form and C-N and C = O in the keto form. This process brings about photo-mediated bistability with multiple physical channels such as dielectric, second-harmonic generation, and ferroelectric polarization. This work further explores this newly developed mechanism of ferroelectric phase transition and highlights the significance of photo-mediated ferroelectric materials for photo-controlled smart devices and bio-sensors.

WGCNA Reveals Hub Genes and Key Gene Regulatory Pathways of the Response of Soybean to Infection by Soybean mosaic virus.

Soybean mosaic virus (SMV) is one of the main pathogens that can negatively affect soybean production and quality. To study the gene regulatory network of soybeans in response to SMV SC15, the resistant line X149 and susceptible line X97 were subjected to transcriptome analysis at 0, 2, 8, 12, 24, and 48 h post-inoculation (hpi). Differential expression analysis revealed that 10,190 differentially expressed genes (DEGs) responded to SC15 infection. Weighted gene co-expression network analysis (WGCNA) was performed to identify highly related resistance gene modules; in total, eight modules, including 2256 DEGs, were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of 2256 DEGs revealed that the genes significantly clustered into resistance-related pathways, such as the plant-pathogen interaction pathway, mitogen-activated protein kinases (MAPK) signaling pathway, and plant hormone signal transduction pathway. Among these pathways, we found that the flg22, Ca2+, hydrogen peroxide (H2O2), and abscisic acid (ABA) regulatory pathways were fully covered by 36 DEGs. Among the 36 DEGs, the gene Glyma.01G225100 (protein phosphatase 2C, PP2C) in the ABA regulatory pathway, the gene Glyma.16G031900 (WRKY transcription factor 22, WRKY22) in Ca2+ and H2O2 regulatory pathways, and the gene Glyma.04G175300 (calcium-dependent protein kinase, CDPK) in Ca2+ regulatory pathways were highly connected hub genes. These results indicate that the resistance of X149 to SC15 may depend on the positive regulation of flg22, Ca2+, H2O2, and ABA regulatory pathways. Our study further showed that superoxide dismutase (SOD) activity, H2O2 content, and catalase (CAT) and peroxidase (POD) activities were significantly up-regulated in the resistant line X149 compared with those in 0 hpi. This finding indicates that the H2O2 regulatory pathway might be dependent on flg22- and Ca2+-pathway-induced ROS generation. In addition, two hub genes, Glyma.07G190100 (encoding F-box protein) and Glyma.12G185400 (encoding calmodulin-like proteins, CMLs), were also identified and they could positively regulate X149 resistance. This study provides pathways for further investigation of SMV resistance mechanisms in soybean.

Application of CMV-IVIg as prophylaxis against cytomegalovirus reactivation in allogeneic hematopoietic stem cell transplantation patients.

Cytomegalovirus (CMV) reactivation remains one of the major and life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Yet, there is still a lack of safe and effective ways to prevent CMV reactivation in allo-HSCT patients. Here, we retrospectively analyzed a cohort of patients who underwent HSCT at our transplant center between 2018 and 2022 to evaluate the efficacy of prophylactic CMV-specific intravenous immunoglobulin (CMV-IVIg) against CMV reactivation. After Propensity Score Matching, the CMV reactivation rate was significantly decreased in the CMV-IVIg group (HR, 2.952; 95% CI,1.492-5.841; P = .002) compared with the control group. Additionally, the time duration of CMV reactivation (P = .001) and bacterial infection rate (P = .013) were significantly lower in the CMV-IVIg group. Moreover, prophylactic CMV-IVIg was more effective in CMV seropositive patients who received ATG as part of GVHD prevention (HR, 8.225; 95% CI,1.809-37.39; P = .006). In conclusion, CMV-IVIg is considered an effective and safe way to prevent CMV reactivation in HSCT recipients, which may be related to the acceleration of immune reconstitution in the early stage after transplantation.

The anti-apoptotic role of Ginkgolide B via mitochondrial permeability transition pore inhibition in retinal ischemia-reperfusion.

This research delves into the effectiveness of Ginkgolide B (GB), a compound from Ginkgo biloba, in combating cell death caused by glaucoma, with a focus on mitochondrial impairment and the mitochondrial permeability transition pore (mPTP). Utilizing models of high intraocular pressure and in vitro glaucoma simulations, the study investigates GB's impact on retinal progenitor cells (RPCs) under oxygen-glucose deprivation/reperfusion (OGD/R) and in a rat glaucoma model. The study methodologies included apoptosis assessment, apoptotic marker analysis via Western blot, and mitochondrial structure and function evaluation. The findings reveal that GB notably decreases apoptosis in RPCs exposed to OGD/R in vitro, and reduces ischemia-reperfusion damage in vivo. GB's protective role is attributed to its ability to preserve mitochondrial integrity, maintain membrane potential, regulate calcium levels, and inhibit mPTP opening. These results underscore GB's potential as a therapeutic agent for acute primary angle-closure glaucoma, highlighting its capability to alleviate mitochondrial damage and apoptosis in RPCs and retinal nerve fiber layer cells.

Biodegradable ferroelectric molecular crystal with large piezoelectric response.

Transient implantable piezoelectric materials are desirable for biosensing, drug delivery, tissue regeneration, and antimicrobial and tumor therapy. For use in the human body, they must show flexibility, biocompatibility, and biodegradability. These requirements are challenging for conventional inorganic piezoelectric oxides and piezoelectric polymers. We discovered high piezoelectricity in a molecular crystal HOCH2(CF2)3CH2OH [2,2,3,3,4,4-hexafluoropentane-1,5-diol (HFPD)] with a large piezoelectric coefficient d33 of ~138 picocoulombs per newton and piezoelectric voltage constant g33 of ~2450 × 10-3 volt-meters per newton under no poling conditions, which also exhibits good biocompatibility toward biological cells and desirable biodegradation and biosafety in physiological environments. HFPD can be composite with polyvinyl alcohol to form flexible piezoelectric films with a d33 of 34.3 picocoulombs per newton. Our material demonstrates the ability for molecular crystals to have attractive piezoelectric properties and should be of interest for applications in transient implantable electromechanical devices.

Modulating the ferroelectric phases in cholesteryl-based organic compounds with perfluoroalkyl tail engineering.

Here, we synthesized a series of cholesteryl-based compounds, whose phases and their transformation can be modulated by temperature and the chain length of the fluoroalkyl moieties. To our knowledge, this is the first time that the phase transition could be modulated with perfluoroalkyl tail engineering in organic single-component ferroelectric crystals.

KDM4C promotes mouse hippocampal neural stem cell proliferation through modulating ApoE expression.

KDM4C is implicated in the regulation of cell proliferation, differentiation, and maintenance in various stem cell types. However, its function in neural stem cells (NSCs) remains poorly understood. Therefore, this study aims to investigate the role and regulatory mechanism of KDM4C in NSCs. Primary hippocampal NSCs were isolated from neonatal mice, and both in vivo and in vitro lentivirus-mediated overexpression of KDM4C were induced in these hippocampal NSCs. Staining results revealed a significant increase in BrdU- and Ki-67-positive cells, along with an elevated number of cells in S phases due to KDM4C overexpression. Subsequently, RNA-seq was employed to analyze gene expression changes following KDM4C upregulation. GO enrichment analysis, KEGG analysis, and GSEA highlighted KDM4C-regulated genes associated with development, cell cycle, and neurogenesis. Protein-protein interaction analysis uncovered that ApoE protein interacts with several genes (top 10 upregulated and downregulated) regulated by KDM4C. Notably, knocking down ApoE mitigated the proliferative effect induced by KDM4C overexpression in NSCs. Our study demonstrates that KDM4C overexpression significantly upregulates ApoE expression, ultimately promoting proliferation in mouse hippocampal NSCs. These findings provide valuable insights into the molecular mechanisms governing neurodevelopment, with potential implications for therapeutic strategies in neurological disorders.

Deep Learning Radiomics Analysis of CT Imaging for Differentiating Between Crohn's Disease and Intestinal Tuberculosis.

This study aimed to develop and evaluate a CT-based deep learning radiomics model for differentiating between Crohn's disease (CD) and intestinal tuberculosis (ITB). A total of 330 patients with pathologically confirmed as CD or ITB from the First Affiliated Hospital of Zhengzhou University were divided into the validation dataset one (CD: 167; ITB: 57) and validation dataset two (CD: 78; ITB: 28). Based on the validation dataset one, the synthetic minority oversampling technique (SMOTE) was adopted to create balanced dataset as training data for feature selection and model construction. The handcrafted and deep learning (DL) radiomics features were extracted from the arterial and venous phases images, respectively. The interobserver consistency analysis, Spearman's correlation, univariate analysis, and the least absolute shrinkage and selection operator (LASSO) regression were used to select features. Based on extracted multi-phase radiomics features, six logistic regression models were finally constructed. The diagnostic performances of different models were compared using ROC analysis and Delong test. The arterial-venous combined deep learning radiomics model for differentiating between CD and ITB showed a high prediction quality with AUCs of 0.885, 0.877, and 0.800 in SMOTE dataset, validation dataset one, and validation dataset two, respectively. Moreover, the deep learning radiomics model outperformed the handcrafted radiomics model in same phase images. In validation dataset one, the Delong test results indicated that there was a significant difference in the AUC of the arterial models (p = 0.037), while not in venous and arterial-venous combined models (p = 0.398 and p = 0.265) as comparing deep learning radiomics models and handcrafted radiomics models. In our study, the arterial-venous combined model based on deep learning radiomics analysis exhibited good performance in differentiating between CD and ITB.

Association between type 2 diabetes mellitus and body composition based on MRI fat fraction mapping.

Purpose: To explore the association between type 2 diabetes mellitus (T2DM) and body composition based on magnetic resonance fat fraction (FF) mapping. Methods: A total of 341 subjects, who underwent abdominal MRI examination with FF mapping were enrolled in this study, including 68 T2DM patients and 273 non-T2DM patients. The FFs and areas of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and abdominal muscle (AM) were measured at the level of the L1-L2 vertebral. The FF of bone marrow adipose tissue (BMAT) was determined by the averaged FF values measured at the level of T12 and L1 vertebral, respectively. The whole hepatic fat fraction (HFF) and pancreatic fat fraction (PFF) were measured based on 3D semi-automatic segmentation on the FF mapping. All data were analyzed by GraphPad Prism and MedCalc. Results: VAT area, VAT FF, HFF, PFF of T2DM group were higher than those of non-T2DM group after adjusting for age and sex (P < 0.05). However, there was no differences in SAT area, SAT FF, BMAT FF, AM area and AM FF between the two groups (P > 0.05). VAT area and PFF were independent risk factors of T2DM (all P < 0.05). The area under the curve (AUC) of the receiver operating characteristic (ROC) for VAT area and PFF in differentiating between T2DM and non-T2DM were 0.685 and 0.787, respectively, and the AUC of PFF was higher than VAT area (P < 0.05). Additionally, in seemingly healthy individuals, the SAT area, VAT area, and AM area were found to be significantly associated with being overweight and/or obese (BMI ≥ 25) (all P < 0.05). Conclusions: In this study, it was found that there were significant associations between T2DM and VAT area, VAT FF, HFF and PFF. In addition, VAT area and PFF were the independent risk factors of T2DM. Especially, PFF showed a high diagnostic performance in discrimination between T2DM and non-T2DM. These findings may highlight the crucial role of PFF in the pathophysiology of T2DM, and it might be served as a potential imaging biomarker of the prevention and treatment of T2DM. Additionally, in individuals without diabetes, focusing on SAT area, VAT area and AM area may help identify potential health risks and provide a basis for targeted weight management and prevention measures.

UTX inhibition suppresses proliferation and promotes apoptosis in patient-derived glioblastoma stem cells by modulating periostin expression.

Glioblastoma stem cells (GSCs) exert a crucial influence on glioblastoma (GBM) development, progression, resistance to therapy, and recurrence, making them an attractive target for drug discovery. UTX, a histone H3K27 demethylase, participates in regulating multiple cancer types. However, its functional role in GSCs remains insufficiently explored. This study aims to investigate the role and regulatory mechanism of UTX on GSCs. Analysis of TCGA data revealed heightened UTX expression in glioma, inversely correlating with overall survival. Inhibiting UTX suppressed GBM cell growth and induced apoptosis. Subsequently, we cultured primary GSCs from three patients, observing that UTX inhibition suppressed cell proliferation and induced apoptosis. RNA-seq was performed to analyze the gene expression changes after silencing UTX in GSCs. The results indicated that UTX-mediated genes were strongly correlated with GBM progression and regulatory tumor microenvironment. The transwell co-cultured experiment showed that silencing UTX in the transwell chamber GSCs inhibited the well plate cell proliferation. Protein-protein interaction analysis revealed that periostin (POSTN) played a role in the UTX-mediated transcriptional regulatory network. Replenishing POSTN reversed the effects of UTX inhibition on GSC proliferation and apoptosis. Our study demonstrated that UTX inhibition hindered POSTN expression by enhancing the H3K27me2/3 level, eventually resulting in inhibiting proliferation and promoting apoptosis of patient-derived GSCs. Our findings may provide a novel and effective strategy for the treatment of GBM.

CCN3/NOV inhibition attenuates oxidative stress-induced apoptosis of mouse neural stem/progenitor cells by blocking the activation of p38 MAPK: An in vitro study.

Neural stem/progenitor cells (NSPCs) hold immense promise in clinical applications, yet the harsh conditions resulting from central nervous system (CNS) injuries, particularly oxidative stress, lead to the demise of both native and transplanted NSPCs. Cellular communication network factor 3 (CCN3) exhibits a protective effect against oxidative stress in various cell types. This study investigates the impact of CCN3 on NSPCs apoptosis induced by oxidative stress. To establish models of primary cultured mouse NSPCs under oxidative stress, we exposed them to 50 µM H2O2 for 4 h. Remarkably, pre-exposing CCN3 exacerbated the H2O2-induced decline in cell viability in a concentration-dependent manner. However, employing gene-targeted siRNA to inhibit CCN3 protected NSPCs against H2O2-induced cell death. Conversely, CCN3 replenishment reversed this protective effect, as evidenced by TUNEL staining, the ratio of Cleaved-caspase-3 to Pro-caspase-3, and Bcl-2/Bax. Further investigations revealed that CCN3 pretreatment increased the phosphorylation level of p38 MAPK, while silencing CCN3 diminished p38 MAPK activation. Ultimately, the impact of changes in CCN3 protein expression on H2O2-induced apoptosis was nullified using anisomycin (a p38 activator) and SB 203580 (a p38 inhibitor). Our findings suggest that CCN3 inhibition prevents H2O2-induced cell death in cultured mouse NSPCs via the p38 pathway. These discoveries may contribute to the development of strategies aimed at enhancing the survival of both endogenous and transplanted NSPCs following CNS oxidative stress insults.

Spatial-temporal evolution of overweight and obesity among Chinese adolescents from 2016 to 2020.

This study examines the spatial-temporal evolution of overweight and obesity among Chinese adolescents aged 14-17. Data from five national surveys conducted between 2016 and 2020 were analyzed to determine distribution patterns and trends. Results showed that overweight and obesity exhibit spatial clustering, with greater severity in the north and less severity in the south. The issue has spread from the northeast to the southwest of Mainland China. Using a local autocorrelation model, the regions were divided into a northern disease cold spot area (Inner Mongolia) and a southern disease hot spot area (Guangxi). Over the past five years, overweight rates among Chinese adolescents have not been effectively curbed, but obesity has shown some success in control and reversal until 2019. Future efforts should focus on the spatial-temporal pattern of disease spread, targeting hotspot areas and abnormal values for regional synergy and precise prevention and control.

The relationship between incidence of cesarean section and physical activity during pregnancy among pregnant women of diverse age groups: Dose-response meta-analysis.

BACKGROUND: There is a lack of evidence related to physical activity and risk of cesarean section (CS) by age and/or weight in pregnant women. OBJECTIVES: To evaluate the effect of physical activity on the incidence of CS and explore the relationship of age and body mass index (BMI) with incidence of CS. SEARCH STRATEGY: A systematic search was conducted in CNKI, WANGFANG, Web of Science, and PubMed from inception to 31 August 2021. SELECTION CRITERIA: Experimental studies were included if the participants were pregnant, if intervention included physical activity and controls received routine prenatal care only, and if primary outcome was CS. DATA COLLECTION AND ANALYSIS: Meta-analysis included a heterogeneity test, data combination, subgroup analysis, forest plot, sensitivity analysis, and dose-response regression analysis. MAIN RESULTS: Sixty-two studies were included. Physical activity during pregnancy decreased the incidence of CS (relative risk [RR] 0.81, 95% confidence interval [CI] 0.74-0.88, P < 0.001). The incidence of CS was lower among the overweight/obese group (RR 0.78, 95% CI 0.65-0.93) compared with the normal weight group (RR 0.82, 95% CI 0.74-0.90). The incidence of CS was lowest among the young age group (RR 0.61, 95% CI 0.46-0.80) compared with the middle age group (RR 0.74, 95% CI 0.64-0.85) and the older age group (RR 0.90, 95% CI 0.82-1.00). The critical value, when age becomes a risk factor for CS, was 31.7 years in the intervention group and 28.5 years in the control group. CONCLUSIONS: Physical activity during pregnancy can reduce the incidence of CS, especially among obese people, and prolong the gestational age span.

Observation of Ferroelectric Lithography on Biodegradable PLA Films.

Ferroelectric lithography, which can purposefully control and pattern ferroelectric domains in the micro-/nanometer scale, has extensive applications in data memories, field-effect transistors, race-track memory, tunneling barriers, and integrated biochemical sensors. In pursuit of mechanical flexibility and light weight, organic ferroelectric polymers such as poly(vinylidene fluoride) are developed; however, they still suffer from complicated stretching processes of film fabrication and poor degradability. These poor features severely hinder their applications. Here, the ferroelectric lithography on the biocompatible and biodegradable poly(lactic acid) (PLA) thin films at room temperature is demonstrated. The semicrystalline PLA thin film can be easily fabricated through the melt-casting method, and the desired domain structures can be precisely written according to the predefined patterns. Most importantly, the coercive voltage (Vc ) of PLA thin film is relatively low (lower than 30 V) and can be further reduced with the decrease of the film thickness. These intriguing behaviors combined with satisfying biodegradability make PLA thin film a desirable candidate for ferroelectric lithography and enable its future application in the field of bioelectronics and biomedicine. This work sheds light on further exploration of ferroelectric lithography on other polymer ferroelectrics as well as their application as nanostructured devices.

Incidence Trends of Inherited Anemias at the Global, Regional, and National Levels Over Three Decades.

Inherited anemia continues to pose a significant public health concern on a global scale, owing to its extensive geographical prevalence, substantial patient population, and profound ramifications. Here, we investigated detailed information on inherited anemias (including thalassemias, thalassemias trait, sickle cell disease, sickle cell trait, G6PD deficiency, and G6PD trait) for the period 1990-2019 from the Global Burden of Disease study. Over the course of three decades, there has been a persistent rise in the incidence of inherited anemias worldwide, culminating in a total of 44,896,026 incident cases in 2019. However, the prevalence of inherited anemias has exhibited a consistent downward trend over successive years. Significantly, these inherited anemias primarily impact females, exhibiting a male-to-female ratio of 1:1.88. Among males, the most prevalent inherited anemia is G6PD deficiency, whereas G6PD trait prevails among females. The incidence rates of inherited anemias and their temporal trend exhibited significant variations across different regions, with Central Sub-Saharan Africa displaying the highest incidence rates and Central Latin America experiencing the most substantial decline. The findings of this study suggest a significant correlation between the Socio-Demographic index (SDI) and incidence rates of inherited anemias, particularly in regions with lower SDI levels such as Africa and South Asia. These results contribute valuable insights for the analysis of global trends in the burden of inherited anemias.

Genome-wide analysis of the SCAMPs gene family of soybean and functional identification of GmSCAMP5 in salt tolerance.

The effect of salt damage on plants is mainly caused by the toxic effect of Na+. Studies showed that the secretory carrier membrane proteins were associated with the Na+ transport. However, the salt tolerance mechanism of secretory carrier protein (SCAMP) in soybean was yet to be defined. In this study, ten potential SCAMP genes distributed in seven soybean chromosomes were identified in the soybean genome. The phylogenetic tree of SCAMP domain sequences of several plants can divide SCAMPs into two groups. Most GmSCAMPs genes contained multiple Box4, MYB and MYC cis-elements indicated they may respond to abiotic stresses. We found that GmSCAMP1, GmSCAMP2 and GmSCAMP4 expressed in several tissues and GmSCAMP5 was significantly induced by salt stress. GmSCAMP5 showed the same expression patterns under NaCl treatment in salt-tolerant and salt-sensitive soybean varieties, but the induced time of GmSCAMP5 in salt-tolerant variety was earlier than that of salt-sensitive variety. To further study the effect of GmSCAMP5 on the salt tolerance of soybean plants, compared to GmSCAMP5-RNAi and EV-Control plants, GmSCAMP5-OE had less wilted leave and higher SPAD value. Compared to empty vector control, less trypan blue staining was observed in GmSCAMP5-OE leaves while more staining in GmSCAMP5-RNAi leaves. The Na+ of GmSCAMP5-RNAi plants leaves under NaCl stress were significantly higher than that in EV-Control plants, while significantly lower Na+ in GmSCAMP5-OE plants than in that EV-Control plants. The contents of leaves K+ of GmSCAMP5-RNAi, EV-Control, and GmSCAMP5-OE plants under NaCl stress were opposite to that of leaves Na+ content. Finally, salt stress-related genes NHX1, CLC1, TIP1, SOD1, and SOS1 in transformed hairy root changed significantly compared with the empty control. The research will provide novel information for study the molecular regulation mechanism of soybean salt tolerance.

Generation of an NSD2-deficient human embryonic stem cell line using CRISPR/Cas9 technology.

NSD2 is a histone methyltransferase (HMT) and is involved in the epigenetic regulation of hematopoiesis and hematological cancers. To understand and illustrate the precise roles of NSD2 in hematopoietic development, here we constructed a human embryonic stem cell (hESC) line with knockout of NSD2 using CRISPR/Cas9-mediated gene targeting. The cell line maintained typical stem cell morphology and normal karyotype. Furthermore, the pluripotency of the cell line was evidenced by high expression level of pluripotency genes and differentiation potential into three germ layers. The cell line provides a good model for studying roles of NSD2 in embryonic development, especially hematopoiesis.

R-Loop Defines Neural Stem/Progenitor Cells During Mouse Neurodevelopment.

Neural stem/progenitor cells (NSPCs) are present in the mammalian brain throughout life and are involved in neurodevelopment and central nervous system repair. Although typical epigenetic signatures, including DNA methylation, histone modifications, and microRNAs, play a pivotal role in regulation of NSPCs, several of the epigenetic regulatory mechanisms of NSPCs remain unclear. Thus, defining a novel epigenetic feature of NSPCs is crucial for developing stem cell therapy to address neurologic disorders caused by injury. In this study, we aimed to define the R-loop, a three-stranded nucleic acid structure, as an epigenetic characteristic of NSPCs during neurodevelopment. Our results demonstrated that R-loop levels change dynamically throughout neurodevelopment. Cells with high levels of R-loops consistently decreased and were enriched in the area of neurogenesis. Additionally, these cells costained with SOX2 during neurodevelopment. Furthermore, these cells with high R-loop levels expressed Ki-67 and exhibited a high degree of overlap with the transcriptional activation markers, H3K4me3, ser5, and H3K27ac. These findings suggest that R-loops may serve as an epigenetic feature for transcriptional activation in NSPCs, indicating their role in gene expression regulation and neurogenesis.

Evidence for the protein leverage hypothesis in preschool children prone to obesity.

BACKGROUND & AIMS: The protein leverage hypothesis (PLH) proposed that strict regulation of protein intake drives energy overconsumption and obesity when diets are diluted by fat and/or carbohydrates. Evidence about the PLH has been found in adults, while studies in children are limited. Thus, we aimed to test the PLH by assessing the role of dietary protein on macronutrients, energy intake, and obesity risk using data from preschool children followed for 1.3 years. METHODS: 553 preschool children aged 2-6 years from the 'Healthy Start' project were included. EXPOSURES: The proportion of energy intake from protein, fat, and carbohydrates collected from a 4-day dietary record. OUTCOMES: Energy intake, BMI z-score, fat mass (FM) %, waist- (WHtR) and hip-height ratio (HHtR). Power function analysis was used to test the leverage of protein on energy intake. Mixture models were used to explore interactive associations of macronutrient composition on all these outcomes, with results visualized as response surfaces on the nutritional geometry. RESULTS: Evidence for the PLH was confirmed in preschool children. The distribution of protein intake (% of MJ, IQR: 3.2) varied substantially less than for carbohydrate (IQR: 5.7) or fat (IQR: 6.3) intakes, suggesting protein intake is most tightly regulated. Absolute energy intake varied inversely with dietary percentage energy from protein (L = -0.14, 95% CI: -0.25, -0.04). Compared to children with high fat or carbohydrate intakes, children with high dietary protein intake (>20% of MJ) had a greater decrease in WHtR and HHtR over the 1.3-year follow-up, offering evidence for the PLH in prospective analysis. But no association was observed between macronutrient distribution and changes in BMI z-score or FM%. CONCLUSIONS: In this study in preschool children, protein intake was the most tightly regulated macronutrient, and energy intake was an inverse function of dietary protein concentration, indicating the evidence for protein leverage. Increases in WHtR and HHtR were principally associated with the dietary protein dilution, supporting the PLH. These findings highlight the importance of protein in children's diets, which seems to have significant implications for childhood obesity risk and overall health.

Organic radical ferroelectric crystals with martensitic phase transition.

Organic martensitic compounds are an emerging type of smart material with intriguing physical properties including thermosalient effect, ferroelasticity, and shape memory effect. However, due to the high structural symmetry and limited design theories for these materials, the combination of ferroelectricity and martensitic transformation has rarely been found in organic systems. Here, based on the chemical design strategies for molecular ferroelectrics, we show a series of asymmetric 1,4,5,8-naphthalenediimide derivatives with the homochiral amine and 2,2,6,6-tetramethylpiperidine-N-oxyl components, which adopt the low-symmetric polar structure and so allow ferroelectricity. Upon H/F substitution, the fluorinated compounds exhibit reversible ferroelectric and martensitic transitions at 399 K accompanied by a large thermal hysteresis of 132 K. This large thermal hysteresis with two competing (meta)-stable phases is further confirmed by density functional theory calculations. The rare combination of martensitic phase transition and ferroelectricity realizes the bistability with two different ferroelectric phases at room temperature. Our finding provides insight into the exploration of martensitic ferroelectric compounds with potential applications in switchable memory devices, soft robotics, and smart actuators.