Conditional ablation of DIS3L2 ribonuclease in pre-meiotic germ cells causes defective spermatogenesis and infertility in male mice.

Rationale: Spermatogenesis is a highly organized cell differentiation process in mammals, involving mitosis, meiosis, and spermiogenesis. DIS3L2, which is primarily expressed in the cytoplasm, is an RNA exosome-independent ribonuclease. In female mice, Dis3l2-deficient oocytes fail to resume meiosis, resulting in arrest at the germinal vesicle stage and complete infertility. However, the role of DIS3L2 in germ cell development in males has remained largely unexplored. Methods: We established a pre-meiotic germ cell conditional knockout mouse model and investigated the biological function of DIS3L2 in spermatogenesis and male fertility through bulk RNA-seq and scRNA-seq analyses. Results: This study unveils that conditional ablation of Dis3l2 in pre-meiotic germ cells with Stra8-Cre mice impairs spermatogonial differentiation and hinders spermatocyte meiotic progression coupled with cell apoptosis. Such conditional ablation leads to defective spermatogenesis and sterility in adults. Bulk RNA-seq analysis revealed that Dis3l2 deficiency significantly disrupted the transcriptional expression pattern of genes related to the cell cycle, spermatogonial differentiation, and meiosis in Dis3l2 conditional knockout testes. Additionally, scRNA-seq analysis indicated that absence of DIS3L2 in pre-meiotic germ cells causes disrupted RNA metabolism, downregulated expression of cell cycle genes, and aberrant expression of spermatogonial differentiation genes, impeding spermatogonial differentiation. In meiotic spermatocytes, loss of DIS3L2 results in disturbed RNA metabolism, abnormal translation, and disrupted meiotic genes that perturb meiotic progression and induce cell apoptosis, leading to subsequent failure of spermatogenesis and male infertility. Conclusions: Collectively, these findings highlight the critical role of DIS3L2 ribonuclease-mediated RNA degradation in safeguarding the correct transcriptome during spermatogonial differentiation and spermatocyte meiotic progression, thus ensuring normal spermatogenesis and male fertility.

An AIE probe for the fluorescence and colorimetric sensing of La3.

In this work, a fluorescent probe N with aggregation-induced emission effect was synthesized by grafting naphtho[2,3-c]furan-1,3-dione and 2-hydrazinylbenzo[d]thiazole. The probe N could recognize La3+ selectively and sensitively accompanied with an obvious fluorescence and color change from green to blue. Moreover, with the help of AIE properties, probe N achieved the detection of La3+ in the solid state.

Patterned Ultraslippery Surfaces of Stainless Steel Prepared by Femtosecond Laser Ablation for Directional Manipulation of Liquid Droplets.

Slippery liquid-infused porous surfaces (SLIPS) have promising applications in chip laboratories, nanofriction power generation, and microfluidics due to their excellent properties such as good hydrophobicity and low adhesion. However, the self-driven stability of conventionally lubricated surfaces is not high, and the velocity of liquid droplets is difficult to regulate. This greatly limits the potential applications of SLIPS. A strategy is offered to prepare microporous structures of SLIPS directly on a stainless-steel substrate using femtosecond laser processing technology as the main means to realize exhibiting smoothness to liquids. At the same time, the principle of bionics is utilized, the porous structure of SLIPS is combined with the groove structure of rice leaves, or porous structures are combined with the wedge structure of shorebird beak to prepare the three-dimensional structure of SLIPS. Droplets exhibit significant individual anisotropy on three-dimensional (3D) SLIPS of leaf-like groove stripe structure in rice, enabling the precise control of droplet motion direction. When droplets are transported in wedge-shaped SLIPS with an asymmetric structure, the wedge edge can limit the direction of droplet motion while squeezing the droplet to generate Laplace pressure gradient, which achieves continuous self-driven transport of droplets. In addition, based on the above two processing strategies, an information transfer device is designed: the splicing of the self-driven transport surface with anisotropic topological channels enables the differential drive for liquid transport, which provides the conditions for the information transfer of the droplets. This strategy not only is simple and efficient but also provides new ideas for the effective development of multifunctional SLIPS as well as lab-on-a-chip and microfluidic domains.

The Type III Effector XopLXcc in Xanthomonas campestris pv. campestris Targets the Proton Pump Interactor 1 and Suppresses Innate Immunity in Arabidopsis.

Xanthomonas campestris pathovar campestris (Xcc) is a significant phytopathogen causing black rot disease in crucifers. Xcc injects a variety of type III effectors (T3Es) into the host cell to assist infection or propagation. A number of T3Es inhibit plant immunity, but the biochemical basis for a vast majority of them remains unknown. Previous research has revealed that the evolutionarily conserved XopL-family effector XopLXcc inhibits plant immunity, although the underlying mechanisms remain incompletely elucidated. In this study, we identified proton pump interactor (PPI1) as a specific virulence target of XopLXcc in Arabidopsis. Notably, the C-terminus of PPI1 and the Leucine-rich repeat (LRR) domains of XopLXcc are pivotal for facilitating this interaction. Our findings indicate that PPI1 plays a role in the immune response of Arabidopsis to Xcc. These results propose a model in which XopLXcc binds to PPI1, disrupting the early defense responses activated in Arabidopsis during Xcc infection and providing valuable insights into potential strategies for regulating plasma membrane (PM) H+-ATPase activity during infection. These novel insights enhance our understanding of the pathogenic mechanisms of T3Es and contribute to the development of effective strategies for controlling bacterial diseases.

Biomarkers for congenital ventricular outflow tract malformations based on maternal serum lipid metabolomics analysis.

BACKGROUND: The congenital ventricular outflow tract malformations (CVOTMs) is a major congenital heart diseases (CHDs) subtype, and its pathogenesis is complex and unclear. Lipid metabolic plays a crucial role in embryonic cardiovascular development. However, due to the limited types of detectable metabolites in previous studies, findings on lipid metabolic and CHDs are still inconsistent, and the possible mechanism of CHDs remains unclear. METHODS: The nest case-control study obtained subjects from the multicenter China Teratology Birth Cohort (CTBC), and maternal serum from the pregnant women enrolled during the first trimester was utilized. The subjects were divided into a discovery set and a validation set. The metabolomics of CVOTMs and normal fetuses were analyzed by targeted lipid metabolomics. Differential comparison, random forest and lasso regression were used to screen metabolic biomarkers. RESULTS: The lipid metabolites were distributed differentially between the cases and controls. Setting the selection criteria of P value < 0.05, and fold change (FC) > 1.2 or < 0.833, we screened 70 differential metabolites. Within the prediction model by random forest and lasso regression, DG (14:0_18:0), DG (20:0_18:0), Cer (d18:2/20:0), Cer (d18:1/20:0) and LPC (0:0/18:1) showed good prediction effects in discovery and validation sets. Differential metabolites were mainly concentrated in glycerolipid and glycerophospholipids metabolism, insulin resistance and lipid & atherosclerosis pathways, which may be related to the occurrence and development of CVOTMs. CONCLUSION: Findings in this study provide a new metabolite data source for the research on CHDs. The differential metabolites and involved metabolic pathways may suggest new ideas for further mechanistic exploration of CHDs, and the selected biomarkers may provide some new clues for detection of COVTMs.

Sulfur and Wavy-Stacking Boosted Superior Lithium Storage in 2D Covalent Organic Frameworks.

2D conjugated covalent organic frameworks (c-COFs) provide an attractive foundation as organic electrodes in energy storage devices, but their storage capability is long hindered by limited ion accessibility within densely π-π stacked interlayers. Herein, two kinds of 2D c-COFs based on dioxin and dithiine linkages are reported, which exhibit distinct in-plane configurations-fully planar and undulated layers. X-ray diffraction analysis reveals wavy square-planar networks in dithiine-bridged COF (COF-S), attributed to curved C─S─C bonds in the dithiine linkage, whereas dioxin-bridged COF (COF-O) features densely packed fully planar layers. Theoretical and experimental results elucidate that the undulated stacking within COF-S possesses an expanded layer distance of 3.8 Å and facilitates effective and rapid Li+ storage, yielding a superior specific capacity of 1305 mAh g-1 at 0.5 A g-1, surpassing that of COF-O (1180 mAh g-1 at 0.5 A g-1). COF-S also demonstrates an admirable cycle life with 80.4% capacity retention after 5000 cycles. As determined, self-expanded wavy-stacking geometry, S-enriched dithiine in COF-S enhances the accessibility and redox activity of Li storage, allowing each phthalocyanine core to store 12 Li+ compared to 8 Li+ in COF-O. These findings underscore the elements and stacking modes of 2D c-COFs, enabling tunable layer distance and modulation of accessible ions.

Associations of dietary pattern, insulin resistance and risk of developing metabolic syndrome among Chinese population.

Evidence regarding the role of dietary patterns in metabolic syndrome (MetS) is limited. The mechanistic links between dietary patterns, insulin resistance, and MetS are not fully understood. This study aimed to evaluate the associations between dietary patterns and the risk of MetS in a Chinese population using a longitudinal design. Data from the China Health and Nutrition Survey, a nationally representative survey, were analyzed. MetS cases were identified based on biomarker data collected in 2009. Factor analysis was employed to identify dietary patterns, while logistic regression models were utilized to examine the association between dietary patterns and MetS. Mediation models were applied to assess multiple mediation effects. Two dietary patterns were revealed by factor analysis. Participants in the higher quartiles of the traditional Chinese dietary pattern had lower odds of MetS than those in the lowest quartile (Q1) (OR = 0.58, 95%CI: 0.48, 0.69 for Q4; OR = 0.75, 95%CI: 0.63, 0.89 for Q3). Conversely, participants in the higher quartiles of the modern Chinese dietary pattern had higher odds of MetS compared to those in the lowest quartile (Q1) (OR = 1.40, 95%CI: 1.17, 1.68 for Q4; OR = 1.27, 95%CI: 1.06, 1.52 for Q3). Significant associations between dietary patterns and MetS were mediated by insulin resistance. Therefore, dietary patterns in Chinese adults are associated with MetS, and these associations appear to be mediated through insulin resistance. These findings underscore the critical role of dietary patterns in the development of MetS and establish a foundation for culturally tailored dietary interventions aimed at reducing rates the prevalence of MetS among Chinese adults.

CIPK11 phosphorylates GSTU23 to promote cold tolerance in Camellia sinensis.

Cold stress negatively impacts the growth, development, and quality of Camellia sinensis (Cs, tea) plants. CBL-interacting protein kinases (CIPK) comprise a pivotal protein family involved in plant development and response to multiple environmental stimuli. However, their roles and regulatory mechanisms in tea plants (Camellia sinensis (L.) O. Kuntze) remain unknown. Here we show that CsCBL-interacting protein kinase 11 (CsCIPK11), whose transcript abundance was significantly induced at low temperatures, interacts and phosphorylates tau class glutathione S-transferase 23 (CsGSTU23). CsGSTU23 was also a cold-inducible gene and has significantly higher transcript abundance in cold-resistant accessions than in cold-susceptible accessions. CsCIPK11 phosphorylated CsGSTU23 at Ser37, enhancing its stability and enzymatic activity. Overexpression of CsCIPK11 in Arabidopsis thaliana resulted in enhanced cold tolerance under freezing conditions, while transient knockdown of CsCIPK11 expression in tea plants had the opposite effect, resulting in decreased cold tolerance and suppression of the C-repeat-binding transcription factor (CBF) transcriptional pathway under freezing stress. Furthermore, the transient overexpression of CsGSTU23 in tea plants increased cold tolerance. These findings demonstrate that CsCIPK11 plays a central role in the signaling pathway to cold signals and modulates antioxidant capacity by phosphorylating CsGSTU23, leading to improved cold tolerance in tea plants.

Development of an AIE-active fluorescent probe for the simultaneous detection of Al3+ and viscosity and imaging in Alzheimer's disease model.

Alzheimer's disease is associated both with imbalances in Al3+ production and changes in viscosity in cells. Their simultaneous measurement could therefore provide valuable insights into Alzheimer's disease pathology. Their simultaneous measurement would therefore be of great value in investigating the pathological mechanism of Alzheimer's disease. We designed a fluorescent probe YM2T with AIE effect that is capable of selectively responding to Al3+ by fluorescence colormetrics and to viscosity by fluorescence "turn on" modes. Additionally, Al3+ and viscosity were simultaneously detected in PC12 cells using the low cytotoxic probe YM2T via blue and green fluorescence channels. More importantly, the YM2T probe was used to image mice with AD. Hence, the YM2T probe shows potential as a useful molecular instrument for studying the pathological impact of Al3+ and viscosity.

DIS3 ribonuclease is essential for spermatogenesis and male fertility in mice.

Spermatogonial stem cell (SSC) self-renewal and differentiation provide foundational support for long-term, steady-state spermatogenesis in mammals. Here, we have investigated the essential role of RNA exosome associated DIS3 ribonuclease in maintaining spermatogonial homeostasis and facilitating germ cell differentiation. We have established male germ-cell Dis3 conditional knockout (cKO) mice in which the first and subsequent waves of spermatogenesis are disrupted. This leads to a Sertoli cell-only phenotype and sterility in adult male mice. Bulk RNA-seq documents that Dis3 deficiency partially abolishes RNA degradation and causes significant increases in the abundance of transcripts. This also includes pervasively transcribed PROMoter uPstream Transcripts (PROMPTs), which accumulate robustly in Dis3 cKO testes. In addition, scRNA-seq analysis indicates that Dis3 deficiency in spermatogonia significantly disrupts RNA metabolism and gene expression, and impairs early germline cell development. Overall, we document that exosome-associated DIS3 ribonuclease plays crucial roles in maintaining early male germ cell lineage in mice.

Optimization of fermentation parameters to improve the biosynthesis of selenium nanoparticles by Bacillus licheniformis F1 and its comprehensive application.

BACKGROUND: Selenium nanoparticles (SeNPs) are increasingly gaining attention due to its characteristics of low toxicity, high activity, and stability. Additionally, Bacillus licheniformis, as a probiotic, has achieved remarkable research outcomes in diverse fields such as medicine, feed processing, and pesticides, attracting widespread attention. Consequently, evaluating the activity of probiotics and SeNPs is paramount. The utilization of probiotics to synthesize SeNPs, achieving large-scale industrialization, is a current hotspot in the field of SeNPs synthesis and is currently the most promising synthetic method. To minimize production costs and maximize yield of SeNPs, this study selected agricultural by-products that are nutrient-rich, cost-effective, and readily available as culture medium components. This approach not only fulfills industrial production requirements but also mitigates the impact on downstream processes. RESULTS: The experimental findings revealed that SeNPs synthesized by B. licheniformis F1 exhibited a spherical morphology with diameters ranging from 110 to 170 nm and demonstrating high stability. Both the secondary metabolites of B. licheniformis F1 and the synthesized SeNPs possessed significant free radical scavenging ability. To provide a more robust foundation for acquiring large quantities of SeNPs via fermentation with B. licheniformis F1, key factors were identified through single-factor experiments and response surface methodology (RSM) include a 2% seed liquid inoculum, a temperature of 37 ℃, and agitation at 180 rpm. Additionally, critical factors during the optimization process were corn powder (11.18 g/L), soybean meal (10.34 g/L), and NaCl (10.68 g/L). Upon validating the optimized conditions and culture medium, B. licheniformis F1 can synthesize nearly 100.00% SeNPs from 5 mmol/L sodium selenite. Subsequently, pilot-scale verification in a 5 L fermentor using the optimized medium resulted in a shortened fermentation time, significantly reducing production costs. CONCLUSION: In this study, the efficient production of SeNPs by the probiotic B. licheniformis F1 was successfully achieved, leading to a significant reduction in fermentation costs. The exploration of the practical applications of this strain holds significant potential and provides valuable guidance for facilitating the industrial-scale implementation of microbial synthesis of SeNPs.

Superconductivity in pressurized trilayer La4Ni3O10-δ single crystals.

The pursuit of discovering new high-temperature superconductors that diverge from the copper-based model1-3 has profound implications for explaining mechanisms behind superconductivity and may also enable new applications4-8. Here our investigation shows that the application of pressure effectively suppresses the spin-charge order in trilayer nickelate La4Ni3O10-δ single crystals, leading to the emergence of superconductivity with a maximum critical temperature (Tc) of around 30 K at 69.0 GPa. The d.c. susceptibility measurements confirm a substantial diamagnetic response below Tc, indicating the presence of bulk superconductivity with a volume fraction exceeding 80%. In the normal state, we observe a strange metal behaviour, characterized by a linear temperature-dependent resistance extending up to 300 K. Furthermore, the layer-dependent superconductivity observed hints at a unique interlayer coupling mechanism specific to nickelates, setting them apart from cuprates in this regard. Our findings provide crucial insights into the fundamental mechanisms underpinning superconductivity, while also introducing a new material platform to explore the intricate interplay between the spin-charge order, flat band structures, interlayer coupling, strange metal behaviour and high-temperature superconductivity.

Risk factors associated with intraoperative persistent hypotension in pancreaticoduodenectomy.

BACKGROUND: Intraoperative persistent hypotension (IPH) during pancreaticoduodenectomy (PD) is linked to adverse postoperative outcomes, yet its risk factors remain unclear. AIM: To clarify the risk factors associated with IPH during PD, ensuring patient safety in the perioperative period. METHODS: A retrospective analysis of patient records from January 2018 to December 2022 at the First Affiliated Hospital of Nanjing Medical University identified factors associated with IPH in PD. These factors included age, gender, body mass index, American Society of Anesthesiologists classification, comorbidities, medication history, operation duration, fluid balance, blood loss, urine output, and blood gas parameters. IPH was defined as sustained mean arterial pressure < 65 mmHg, requiring prolonged deoxyepinephrine infusion for > 30 min despite additional deoxyepinephrine and fluid treatments. RESULTS: Among 1596 PD patients, 661 (41.42%) experienced IPH. Multivariate logistic regression identified key risk factors: increased age [odds ratio (OR): 1.20 per decade, 95% confidence interval (CI): 1.08-1.33] (P < 0.001), longer surgery duration (OR: 1.15 per additional hour, 95%CI: 1.05-1.26) (P < 0.01), and greater blood loss (OR: 1.18 per 250-mL increment, 95%CI: 1.06-1.32) (P < 0.01). A novel finding was the association of arterial blood Ca2+ < 1.05 mmol/L with IPH (OR: 2.03, 95%CI: 1.65-2.50) (P < 0.001). CONCLUSION: IPH during PD is independently associated with older age, prolonged surgery, increased blood loss, and lower plasma Ca2+.

Integrated Bioinformatics Analysis Reveals the Aberrantly Methylated Differentially Expressed Genes in Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) causes heart failure and sudden death. Epigenetics is crucial in cardiomyopathy susceptibility and progression; however, the relationship between epigenetics, particularly DNA methylation, and DCM remains unknown. Therefore, this study identified aberrantly methylated differentially expressed genes (DEGs) associated with DCM using bioinformatics analysis and characterized their clinical utility in DCM. DNA methylation expression profiles and transcriptome data from public datasets of human DCM and healthy control cardiac tissues were obtained from the Gene Expression Omnibus public datasets. Then an epigenome-wide association study was performed. DEGs were identified in both DCM and healthy control cardiac tissues. In total, 3,353 cytosine-guanine dinucleotide sites annotated to 2,818 mRNAs were identified, and 479 DCM-related genes were identified. Subsequently, core genes were screened using logistic, least absolute shrinkage and selection operator, random forest, and support vector machine analyses. The overlapping of these genes resulted in DEGs with abnormal methylation patterns. Cross-tabulation analysis identified 8 DEGs with abnormal methylation. Real-time quantitative polymerase chain reaction confirmed the expression of aberrantly methylated DEGs in mice. In DCM murine cardiac tissues, the expressions of SLC16A9, SNCA, PDE5A, FNDC1, and HTRA1 were higher compared to normal murine cardiac tissues. Moreover, logistic regression model associated with aberrantly methylated DEGs was developed to evaluate the diagnostic value, and the area under the receiver operating characteristic curve was 0.949, indicating that the diagnostic model could reliably distinguish DCM from non-DCM samples. In summary, our study identified 5 DEGs through integrated bioinformatic analysis and in vivo experiments, which could serve as potential targets for further comprehensive investigation.

Application of Bimetallic Hydroxide/Graphene Composites in Wastewater Treatment.

The increasing discharge of antibiotic wastewater leads to increasing water pollution. Most of these antibiotic wastewaters are persistent, strongly carcinogenic, easy to bioaccumulate, and have other similar characteristics, seriously jeopardizing human health and the ecological environment. As a commonly used wastewater treatment technology, non-homogeneous electro-Fenton technology avoids the hazards of H2O2 storage and transportation as well as the loss of desorption and reabsorption. It also facilitates electron transfer on the electrodes and the reduction of Fe3+ on the catalysts, thereby reducing sludge production. However, the low selectivity and poor activity of electro-synthesized H2O2, along with the low concentration of its products, combined with the insufficient activity of electrically activated H2O2, results in a low ∙OH yield. To address the above problems, composites of layered bimetallic hydroxides and carbon materials were designed and prepared in this paper to enhance the performance of electro-synthesized H2O2 and non-homogeneous electro-Fenton by changing the composite mode of the materials. Three composites, NiFe layered double hydroxides (LDHs)/reduced graphene oxide (rGO), NiMn LDHs/rGO, and NiMnFe LDHs/rGO, were constructed by the electrostatic self-assembly of exfoliated LDHs with few-layer graphene. The LDHs/rGO was loaded on carbon mats to construct the electro-Fenton cathode materials, and the non-homogeneous electro-Fenton oxidative degradation of organic pollutants was realized by the in situ electrocatalytic reduction of O2 to ∙OH. Meanwhile, the effects of solution pH, applied voltage, and initial concentration on the performance of non-homogeneous electro-Fenton were investigated with ceftazidime as the target pollutant, which proved that the cathode materials have an excellent electro-Fenton degradation effect.

Loss of DIS3L in the initial segment is dispensable for sperm maturation in the epididymis and male fertility.

DIS3L, a catalytic exoribonuclease associated with the cytoplasmic exosome complex, degrades cytoplasmic RNAs and is implicated in cancers and certain other diseases in humans. Epididymis plays a pivotal role in the transport, maturation, and storage of sperm required for male fertility. However, it remains unclear whether DIS3L-mediated cytoplasmic RNA degradation plays a role in epididymis biology and functioning. Herein, we fabricated a Dis3l conditional knockout (Dis3l cKO) mouse line in which DIS3L was ablated from the principal cells of the initial segment (IS). Morphological analyses showed that spermatogenesis and IS differentiation occurred normally in Dis3l cKO mice. Additionally, the absence of DIS3L had no dramatic influence on the transcriptome of IS. Moreover, the sperm count, morphology, motility, and acrosome reaction frequency in Dis3l cKO mice were comparable to that of the control, indicating that the Dis3l cKO males had normal fertility. Collectively, our genetic model demonstrates that DIS3L inactivation in the IS is nonessential for sperm maturation and male fertility.

Functional Analysis of Type III Effectors in Xanthomonas campestris pv. campestris Reveals Distinct Roles in Modulating Arabidopsis Innate Immunity.

Xanthomonas campestris pv. campestris (Xcc) is a significant phytopathogen causing black rot disease in crucifers. Its virulence relies heavily on the type III secretion system (T3SS), facilitating effector translocation into plant cells. The type III effectors (T3Es) disrupt cellular processes, promoting pathogen proliferation. However, only a few T3Es from Xcc have been thoroughly characterized. In this study, we further investigated two effectors using the T3Es-deficient mutant and the Arabidopsis protoplast system. XopE2Xcc triggers Arabidopsis immune responses via an unidentified activator of the salicylic acid (SA) signaling pathway, whereas XopLXcc suppresses the expression of genes associated with patterns-triggered immunity (PTI) and the SA signaling pathway. These two effectors exert opposing effects on Arabidopsis immune responses. Additionally, we examined the relationship between the specific domains and functions of these two effector proteins. Our findings demonstrate that the N-myristoylation motif and N-terminal domain are essential for the subcellular localization and virulence of XopE2Xcc and XopLXcc, respectively. These novel insights enhance our understanding of the pathogenic mechanisms of T3Es and contribute to developing effective strategies for controlling bacterial disease.

The Modulation of Compositional Heterogeneity for Controlling Shear Banding in Co-P Metallic Nanoglasses.

Shear banding is much dependent on the glass-glass interfaces (GGIs) in metallic nanoglasses (NGs). Nevertheless, the current understanding of the glass phase of GGIs is not well established for controlling the shear banding in NGs. In this study, Co-P NGs are investigated by molecular dynamics simulations to reveal the phenomenon of elemental segregation in the GGI regions where the content of Co is dominant. Specifically, Co segregation results in the formation of GGIs, whose atomic structures are comparatively less dense than those present in the interiors of glassy grains. It is suggested that the Co segregation significantly reduces the shear resistance of GGIs. Thus, such compositional heterogeneity influences the mechanical properties of Co-P NGs. Particularly, shear banding is much altered through enhancing the Co segregation in the GGI regions, which leads to improvements in the ductility of Co-P NGs. This study advances knowledge of the formation of the GGI phase in NGs, which could enable GGI engineering in enhancing the mechanical properties of NGs.

The maternal drug exposure birth cohort (DEBC) in China.

Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes, and establish a human biospecimen biobank. Here we describe the process of establishing DEBC and show that the drug exposure rate in the first trimester of pregnant women in DEBC (n = 112,986) is 30.70%. Among the drugs used, dydrogesterone and progesterone have the highest exposure rates, which are 11.97% and 10.82%, respectively. The overall incidence of adverse pregnancy outcomes is 13.49%. Dydrogesterone exposure during the first trimester is correlated with higher incidences of stillbirth, preterm birth, low birth weight, and birth defects, along with a lower incidence of miscarriage/abortion. Due to the limitations of this cohort study, causative conclusions cannot be drawn. Further follow-up and in-depth data analysis are planned for future studies.