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By analyzing imputed genetic data for 42 human traits, Doug Speed and colleagues derive a model that describes how heritability varies with minor allele frequency, linkage disequilibrium and genotype certainty. Using this model, they show that common SNPs contribute substantially more heritability than previously thought. SNP heritability, the proportion of phenotypic variance explained by SNPs, has been reported for many hundreds of traits. Its estimation requires strong prior assumptions about the distribution of heritability across the genome, but current assumptions have not been thoroughly tested. By analyzing imputed data for a large number of human traits, we empirically derive a model that more accurately describes how heritability varies with minor allele frequency (MAF), linkage disequilibrium (LD) and genotype certainty. Across 19 traits, our improved model leads to estimates of common SNP heritability on average 43% (s.d. 3%) higher than those obtained from the widely used software GCTA and 25% (s.d. 2%) higher than those from the recently proposed extension GCTA-LDMS. Previously, DNase I hypersensitivity sites were reported to explain 79% of SNP heritability; using our improved heritability model, their estimated contribution is only 24%.

We studied the magnetization evolution in three-dimensional chiral nanostructures, including nanotubes and circularly curved thin films, by micromagnetic simulations. We found that in a nanotube skyrmions can be formed by broken of the helical stripes on the left and right sides of the nanotube, and the formation of skyrmions doesn’t correspond to any abrupt change of topological number. Skyrmions can exist in a large range of magnetic field, and the thinner nanotube has a larger field range for skyrmion existence. The configuration of a skyrmion in nanotubes is different from the one in thin film. From the outer to the inner circular layer, the size of the skyrmion becomes larger, and the deformation becomes more obvious. In circularly curved magnetic films with fixed arc length, there are three kinds of hysteresis processes are found. For the curved films with a large radius, the magnetization evolution behavior is similar to the case in two-dimensional thin films. For the curved films with a small radius, the skyrmions are created by broken of the helical stripes on the left and right sides of the curved film. For the curved film with a medium radius, no skyrmion is formed in the hysteresis process.

This study examines consumers’ reactions to the communication styles of chatbots during failed service experiences. The current study explores whether the communication style adopted by a chatbot impacts consumer satisfaction and behavior intention and how expectancy violations can moderate these relationships in the service context. A pre-test examined the validity of the stimuli of chatbots that were either task-oriented or social-oriented after consumers encountered service failure. For more information, the experiment was designed to manipulate the AI-based chatbot agent’s process and style of communication and measure the role of expectancy violations. The main experiment results showed that interactions with social-oriented communication style chatbots enhance the level of consumers’ interaction satisfaction and intention of behavior. Respondents experienced a higher perception of warmth when interacting with social-oriented communication style chatbots than task-oriented. Moreover, expectancy violation moderates the mediation of warmth on the relationship between the chatbot’s communication style/type and interaction satisfaction, trust, and intention of patronage. Setting chatbots’ communication styles to be social-oriented can help reduce negative emotions among consumers caused by service failure; specifically, the perception of warmth created by the social-oriented communication style can alleviate negative evaluations of service agents and companies, such as dissatisfaction and loss of interest. Therefore, in managerial practice, the firm should choose the social-oriented communication style chatbot agent to recover the customer relationship after a service failure.

This study aimed to develop an effective individualized predictive nomogram for the occurrence of necrotizing enterocolitis (NEC) in premature infants with early-onset sepsis (EOS). A total of 238 premature infants meeting the inclusion criteria of gestational age < 37 weeks and EOS diagnosis, including 71 with NEC and 167 without NEC (NEC incidence: 29.8%), treated at the First Hospital Affiliated to Army Medical University from January, 2016, to September, 2024 were retrospectively enrolled as a modeling cohort. Additionally, 205 preterm with EOS (53 with NEC and 152 with non-NEC, NEC incidence: 25.9%), who were treated at Liaocheng People’s Hospital from January, 2014, to September, 2024 were retrospectively enrolled as a validation cohort to assess the predictive efficacy of the model. LASSO-Logistic regression analysis were applied to screen independent predictors, which were subsequently incorporated into a nomogram constructed using R software. Model performance was assessed through receiver operating characteristic analysis, calibration curves, decision curve analysis (DCA), and clinical impact curves (CIC). Lasso-logistic regression identified four independent predictors of NEC in premature infants with EOS: chorioamnionitis (OR = 3.07, 95% CI : 1.26–7.48, p  = 0.013), neonatal respiratory distress syndrome (OR = 2.20, 95% CI : 1.10–4.41, p  = 0.027), lactate level (OR = 1.96, 95% CI : 1.48–2.58, p  < 0.001), and white blood cell (WBC) count (OR = 0.89, 95% CI : 0.83–0.95, p  < 0.001). These factors were integrated into the nomogram. The nomogram demonstrated excellent discriminative ability with the area under the receiver operating curve of 0.848 (95% CI : 0.793–0.903, sensitivity: 0.820, specificity: 0.761) in the modeling cohort and 0.825 (95% CI : 0.764–0.887, sensitivity: 0.750, specificity: 0.755) in the validation cohort, enabling early risk stratification for targeted clinical monitoring. Calibration curves confirmed good agreement between predicted and observed NEC probabilities (modeling cohort: χ 2  = 3.539, df = 8, p  = 0.896; validation cohort: χ 2  = 12.769, df = 8, p  = 0.120). DCA and CIC further verified the nomogram’s high net clinical benefit, confirming its utility in guiding clinical decision-making. This study establishes a nomogram based on four readily accessible variables to predict NEC in premature infants with EOS. With robust predictive performance, this tool enables early risk stratification of high-risk infants, facilitating timely and targeted monitoring and intervention.

Major depression (MD) is a heterogeneous disorder; however, the extent to which genetic factors distinguish MD patient subgroups (genetic heterogeneity) remains uncertain. This study sought evidence for genetic heterogeneity in MD. Using UK Biobank cohort, the authors defined 16 MD subtypes within eight comparison groups (vegetative symptoms, symptom severity, comorbid anxiety disorder, age at onset, recurrence, suicidality, impairment, and postpartum depression; N ~ 3000–47000). To compare genetic component of these subtypes, subtype-specific genome-wide association studies were performed to estimate SNP-heritability, and genetic correlations within subtype comparison and with other related disorders/traits. The findings indicated that MD subtypes were divergent in their SNP-heritability, and genetic correlations both within subtype comparisons and with other related disorders/traits. Three subtype comparisons (vegetative symptoms, age at onset, and impairment) showed significant differences in SNP-heritability; while genetic correlations within subtype comparisons ranged from 0.55 to 0.86, suggesting genetic profiles are only partially shared among MD subtypes. Furthermore, subtypes that are more clinically challenging, e.g., early-onset, recurrent, suicidal, more severely impaired, had stronger genetic correlations with other psychiatric disorders. MD with atypical-like features showed a positive genetic correlation (+0.40) with BMI while a negative correlation (−0.09) was found in those without atypical-like features. Novel genomic loci with subtype-specific effects were identified. These results provide the most comprehensive evidence to date for genetic heterogeneity within MD, and suggest that the phenotypic complexity of MD can be effectively reduced by studying the subtypes which share partially distinct etiologies.

Expanded newborn screening facilitates early identification and intervention of patients with inborn errors of metabolism (IEMs), There is a lack of disease spectrum data for many areas in China. To determine the disease spectrum and genetic characteristics of IEMs in Xi'an city of Shaanxi province in northwest China, 146152 newborns were screening by MSMS from January 2014 to December 2019 and 61 patients were referred to genetic analysis by next generation sequencing (NGS) and validated by Sanger sequencing. Seventy-five newborns and two mothers were diagnosed with IEMs, with an overall incidence of 1:1898 (1:1949 without mothers). There were 35 newborns with amino acidemias (45.45%, 1:4176), 28 newborns with organic acidurias (36.36%, 1:5220), and 12 newborns and two mothers with FAO disorders (18.18%; 1:10439 or 1:12179 without mothers). Phenylketonuria and methylmalonic acidemia were the two most common disorders, accounting for 65.33% (49/75) of all confirmed newborn. Some hotspot mutations were observed for several IEMs, including PAH gene c.728G>A for phenylketonuria; MMACHC gene c.609G>A and c.567dupT, MMUT gene c.323G>A for methylmalonic acidemia and SLC25A13 gene c.852_855del for citrin deficiency. Our study provides effective clinical guidance for the popularization and application of expanded newborn screening, genetic screening, and genetic counseling of IEMs in this region.

The fragile ecological environment of the Qinghai–Tibet Plateau (QTP) is significantly affected by human activities. This study employed a self-organizing map (SOM) for cluster analysis and positive matrix factorization (PMF) to trace the source of potentially toxic elements (PTEs) in the surface water of rivers. The results revealed that the average concentration of PTEs in the rivers was generally low. However, at some sampling points, especially in areas near the Qarhan Salt Lake, the content of Cu, Hg, and Ni were high. The water quality index (WQI), contamination factor (CF), and modified contamination index (mCd) identified good water quality, while potential Ni in the Quanji and Golmud River basins were the primary contaminants of concern. The potential ecological risk index (PERI) showed a low ecological risk. The SOM yielded four clusters of water PTEs, including Hg, Cu-Ni, Pb-Cd-Zn, and As. PMF model further revealed PTE sources, with industrial sources (39.73%) as the primary anthropogenic factor, followed by natural weathering (33.44%), vehicle emissions (21.52%), and atmospheric deposition (5.31%). This study laid the foundation for the ecological monitoring of rivers on the QTP and provided a reference for balancing industrial development and ecological protection in Qarhan Salt Lake areas.

Extremely metal-poor galaxies with metallicity below 10% of the solar value in the local universe are the best analogues to investigating the interstellar medium at a quasi-primitive environment in the early universe. In spite of the ongoing formation of stars in these galaxies, the presence of molecular gas (which is known to provide the material reservoir for star formation in galaxies such as our Milky Way) remains unclear. Here we report the detection of carbon monoxide (CO), the primary tracer of molecular gas, in a galaxy with 7% solar metallicity, with additional detections in two galaxies at higher metallicities. Such detections offer direct evidence for the existence of molecular gas in these galaxies that contain few metals. Using archived infrared data, it is shown that the molecular gas mass per CO luminosity at extremely low metallicity is approximately one-thousand times the Milky Way value. Extremely metal-poor galaxies in the local universe are the best analogues to investigating the interstellar medium at a quasi-primitive environment in the early universe. Here, the authors detect CO emission in a galaxy at 7% solar metallicity, offering direct evidence for the presence of molecular gas.

Mitochondrial DNA (mtDNA) variants influence the risk of late-onset human diseases, but the reasons for this are poorly understood. Undertaking a hypothesis-free analysis of 5,689 blood-derived biomarkers with mtDNA variants in 16,220 healthy donors, here we show that variants defining mtDNA haplogroups Uk and H4 modulate the level of circulating N -formylmethionine (fMet), which initiates mitochondrial protein translation. In human cytoplasmic hybrid (cybrid) lines, fMet modulated both mitochondrial and cytosolic proteins on multiple levels, through transcription, post-translational modification and proteolysis by an N-degron pathway, abolishing known differences between mtDNA haplogroups. In a further 11,966 individuals, fMet levels contributed to all-cause mortality and the disease risk of several common cardiovascular disorders. Together, these findings indicate that fMet plays a key role in common age-related disease through pleiotropic effects on cell proteostasis. The association between certain mitochondrial DNA variants and increased risk of late-onset diseases in humans could be explained by a direct role of mitochondrial DNA in the regulation of cellular proteostasis.

To discover novel potent cytotoxic diterpenoids, a series of hybrids of dehydroabietic acid containing 1,2,3-triazole moiety were designed and synthesized. The target compounds were characterized by means of FT-IR, 1H NMR, 13C NMR, ESI-MS and elemental analysis techniques. The in vitro cytotoxicity of these compounds was evaluated by standard MTT (methyl thiazolytetrazolium) assay against CNE-2 (nasopharynx), HepG2 (liver), HeLa (epithelial cervical), BEL-7402 (liver) human carcinoma cell lines and human normal liver cell (HL-7702). The screening results revealed that most of the hybrids showed significantly improved cytotoxicity over parent compound DHAA. Among them, [1-(3-fluorobenzyl)-1H-1,2,3-triazole-4-yl]dehydroabietic acid methyl ester (3c), and [1-(2-nitrobenzyl)-1H-1,2,3-triazole-4-yl]dehydroabietic acid methyl ester (3k) displayed better antiproliferative activity with IC50 (50% inhibitory concentration) values of 5.90 ± 0.41 and 6.25 ± 0.37 µM toward HepG2 cells compared to cisplatin, while they exhibited lower cytotoxicity against HL-7702. Therefore, the 1,2,3-triazole-hybrids could be a promising strategy for the synthesis of antitumor diterpenoids and it also proved the essential role of 1,2,3-triazole moiety of DHAA in the biological activity.