A deep learning system for myopia onset prediction and intervention effectiveness evaluation in children.

The increasing prevalence of myopia worldwide presents a significant public health challenge. A key strategy to combat myopia is with early detection and prediction in children as such examination allows for effective intervention using readily accessible imaging technique. To this end, we introduced DeepMyopia, an artificial intelligence (AI)-enabled decision support system to detect and predict myopia onset and facilitate targeted interventions for children at risk using routine retinal fundus images. Based on deep learning architecture, DeepMyopia had been trained and internally validated on a large cohort of retinal fundus images (n = 1,638,315) and then externally tested on datasets from seven sites in China (n = 22,060). Our results demonstrated robustness of DeepMyopia, with AUCs of 0.908, 0.813, and 0.810 for 1-, 2-, and 3-year myopia onset prediction with the internal test set, and AUCs of 0.796, 0.808, and 0.767 with the external test set. DeepMyopia also effectively stratified children into low- and high-risk groups (p < 0.001) in both test sets. In an emulated randomized controlled trial (eRCT) on the Shanghai outdoor cohort (n = 3303) where DeepMyopia showed effectiveness in myopia prevention compared to NonCyc-based model, with an adjusted relative reduction (ARR) of -17.8%, 95% CI: -29.4%, -6.4%. DeepMyopia-assisted interventions attained quality-adjusted life years (QALYs) of 0.75 (95% CI: 0.53, 1.04) per person and avoided blindness years of 13.54 (95% CI: 9.57, 18.83) per 1 million persons compared to natural lifestyle with no active intervention. Our findings demonstrated DeepMyopia as a reliable and efficient AI-based decision support system for intervention guidance for children.

Prognostic genome and transcriptome signatures in colorectal cancers.

Colorectal cancer is caused by a sequence of somatic genomic alterations affecting driver genes in core cancer pathways1. Here, to understand the functional and prognostic impact of cancer-causing somatic mutations, we analysed the whole genomes and transcriptomes of 1,063 primary colorectal cancers in a population-based cohort with long-term follow-up. From the 96 mutated driver genes, 9 were not previously implicated in colorectal cancer and 24 had not been linked to any cancer. Two distinct patterns of pathway co-mutations were observed, timing analyses identified nine early and three late driver gene mutations, and several signatures of colorectal-cancer-specific mutational processes were identified. Mutations in WNT, EGFR and TGFß pathway genes, the mitochondrial CYB gene and 3 regulatory elements along with 21 copy-number variations and the COSMIC SBS44 signature correlated with survival. Gene expression classification yielded five prognostic subtypes with distinct molecular features, in part explained by underlying genomic alterations. Microsatellite-instable tumours divided into two classes with different levels of hypoxia and infiltration of immune and stromal cells. To our knowledge, this study constitutes the largest integrated genome and transcriptome analysis of colorectal cancer, and interlinks mutations, gene expression and patient outcomes. The identification of prognostic mutations and expression subtypes can guide future efforts to individualize colorectal cancer therapy.

Global citrus root microbiota unravels assembly cues and core members.

Introduction: Citrus is one of the most important fruit crops worldwide, and the root-associated microbiota can have a profound impact on tree health and growth. Methods: In a collaborative effort, the International Citrus Microbiome Consortium investigated the global citrus root microbiota with samples collected from nine citrus-producing countries across six continents. We analyzed 16S rDNA and ITS2 amplicon sequencing data to identify predominant prokaryotic and fungal taxa in citrus root samples. Comparative analyses were conducted between root-associated microbial communities and those from the corresponding rhizosphere and bulk soil samples. Additionally, genotype-based group-wise comparisons were performed to assess the impact of citrus genotype on root microbiota composition. Results: Ten predominant prokaryotic phyla, containing nine bacterial phyla including Proteobacteria, Actinobacteria, Acidobacteria, and Bacteroidetes and one archaeal phylum (Thaumarchaeota), and multiple fungal phyla including Ascomycota and Basidiomycota were identified in the citrus root samples. Compared with the microbial communities from the corresponding rhizosphere and bulk soil samples from the same trees, the prokaryotic and fungal communities in the roots exhibited lower diversity and complexity but greater modularity compared to those in the rhizosphere. In total, 30 root-enriched and 150 root-depleted genera in bacterial community were identified, whereas 21 fungal genera were enriched, and 147 fungal genera were depleted in the root niche compared with the rhizosphere. The citrus genotype significantly affected the root prokaryotic and fungal communities. In addition, we have identified the core root prokaryotic genera comprising Acidibacter, Allorhizobium, Bradyrhizobium, Chitinophaga, Cupriavidus, Devosia, Dongia, Niastella, Pseudomonas, Sphingobium, Steroidobacter and Streptomyces, and the core fungal genera including Acrocalymma, Cladosporium, Fusarium, Gibberella, Mortierella, Neocosmospora and Volutella. The potential functions of these core genera of root microbiota were predicted. Conclusion: Overall, this study provides new insights into the assembly of microbial communities and identifies core members of citrus root microbiota across a wide geographic range. The findings offer valuable information for manipulating root microbiota to enhance plant growth and health.

Substrates mimicking the blastocyst geometry revert pluripotent stem cell to naivety.

Naive pluripotent stem cells have the highest developmental potential but their in vivo existence in the blastocyst is transient. Here we report a blastocyst motif substrate for the in vitro reversion of mouse and human pluripotent stem cells to a naive state. The substrate features randomly varied microstructures, which we call motifs, mimicking the geometry of the blastocyst. Motifs representing mouse-blastocyst-scaled curvature ranging between 15 and 62 mm-1 were the most efficient in promoting reversion to naivety, as determined by time-resolved correlative analysis. In these substrates, apical constriction enhances E-cadherin/RAC1 signalling and activates the mechanosensitive nuclear transducer YAP, promoting the histone modification of pluripotency genes. This results in enhanced levels of pluripotency transcription factor NANOG, which persist even after cells are removed from the substrate. Pluripotent stem cells cultured in blastocyst motif substrates display a higher development potential in generating embryoid bodies and teratomas. These findings shed light on naivety-promoting substrate design and their large-scale implementation.

Modulation of Kondo Behavior in a Two-Dimensional Epitaxial Bilayer Bi(111)/Fe3GeTe2 Moiré Heterostructure.

Artificial two-dimensional (2D) moiré superlattices provide a platform for generating exotic quantum matter or phenomena. Here, an epitaxial heterostructure composed of bilayer Bi(111) and an Fe3GeTe2 substrate with a zero-twist angle is acquired by molecular beam epitaxy. Scanning tunneling microscopy and spectroscopy studies reveal the spatially tailored Kondo resonance and interfacial magnetism within this moiré superlattice. Combined with first-principles calculations, it is found that the modulation effect of the moiré superlattice originates from the interfacial orbital hybridization between Bi and Fe atoms. Our work provides a tunable platform for strong electron correlation studies to explore 2D artificial heavy Fermion systems and interface magnetism.

Efficacy of weekly dose of 1% atropine for myopia control in Chinese children.

PURPOSE: To assess the effect of weekly 1% atropine use on children's myopia progression and whether the effect is sustainable. METHODS: Medical records of myopic children aged 3-15 years receiving weekly 1% atropine for more than 1 year were retrospectively reviewed. Axial length (AL) and spherical equivalent refraction (SER) at every visit were collected. The changes in AL or SER over time were analysed using generalised estimating equation. The related factors of myopic progression were performed by multiple linear regression. The performance of short-term AL change to predict atropine-poor responders (AL change >0.2 mm/year) was assessed using receiver operating characteristic analysis. RESULTS: A total of 694 participants with a mean age of 8.83 years were included. The participants with follow-up time reached 1, 2, 3 and 4 years were 256 (36.9%), 250 (36.0%), 143 (20.6%) and 45 (6.5%) separately. The cumulative change in AL was 0.05 mm, 0.24 mm, 0.47 mm, 0.56 mm separately for 1-year, 2-year, 3-year and 4- year treatment. Approximate 0.20 mm elongation per year was observed since the second-year of the treatment. Older age and lower initial myopic refraction were independently associated with less myopic progression. A decrease in AL of more than 0.04 mm during the initial 2 months could serve as an indicator for identifying fast progressors (AL change >0.2 mm/year) over a 2-year period, with sensitivity and specificity rates of 0.78 and 0.73, respectively. CONCLUSION: Weekly 1% atropine may be a potentially effective treatment with longer lasting effects for children with myopia control especially in those with older age and lower myopia.

Smartwatch Measures of Outdoor Exposure and Myopia in Children.

Importance: Time spent outdoors has been proven effective in preventing myopia, but little is known about the association of outdoor exposure patterns with myopia. Objective: To examine the association of outdoor exposure patterns with myopic shift in children. Design, Setting, and Participants: This 1-year prospective cohort study from December 2017 to December 2018 was a secondary analysis of a cluster-randomized trial (Shanghai Time Outside to Reduce Myopia [STORM]). STORM was a school-based intervention study, recruiting 16 schools from 8 districts in Shanghai, from October 2016 to December 2018. Children without myopia at baseline who consistently wore a smartwatch for a minimum of 6 hours daily, sustained for at least 90 days, and who had complete information were included. Data analysis was performed from December 2017 to December 2018. Exposures: The outdoor exposure pattern was defined as the episode of time outdoors and instant sunlight intensity over a continuous period. Main Outcomes and Measures: Myopic shift was defined as the absolute change in refraction between the initial spherical equivalence and the follow-up spherical equivalence. Results: This study included 2976 students (mean [SD] age, 7.2 [0.6] years; 1525 girls [51.2%]). The mean (SD) daily time outdoors was 90 (28) minutes, and the mean (SD) sunlight intensity was 2345 (486) lux. Of the 12 outdoor exposure patterns, the major outdoor exposure patterns were time outdoors with at least 15 minutes, accounting for 74.9% of minutes (33 677 584 of 45 016 800 minutes). Only patterns with at least 15 minutes accompanied with no less than 2000 lux were associated with less myopic shift in refraction (for ≥15 minutes and 2000 to 3999 lux, -0.007 diopter [D] [95% CI, -0.011 to -0.002 D]; for ≥15 minutes and ≥4000 lux, -0.006 D [95% CI, -0.010 to -0.002 D]). The isotemporal substitution of patterns with at least 15 minutes and 2000 lux for other outdoor exposure patterns was positively associated with less myopic shift. Conclusions and Relevance: In this 1-year prospective cohort study of children with smartwatches, continuous outdoor exposure with at least 15 minutes accompanied with no less than 2000 lux sunlight intensity was associated with less myopic shift. These findings suggest that future outdoor interventions should focus not only on the overall time outdoors but also on the effective outdoor exposure patterns, as a means to effectively prevent myopia in children.

The differences of metabolic profiles, socioeconomic status and diabetic retinopathy in U.S. working-age and elderly adults with diabetes: results from NHANES 1999-2018.

AIMS: Controlled metabolic factors and socioeconomic status (SES) was crucial for prevention of diabetic retinopathy (DR). The study aims to assess the metabolic factors control and SES among working-age adults (18-64 years) with diabetes compared to older adults (65 years and older). METHODS: Totals of 6738 participants with self-reported diagnosed diabetes from National Health and Nutrition Examination Survey were included, of whom 3482 were working-age and 3256 were elderly. The prevalence of DR, metabolic factors control, and the impact of SES and diabetic duration on DR was estimated. Subgroup analysis among working-age adults was employed across different diabetic duration and SES level. RESULTS: The prevalence of DR was 20.8% among working-age adults and 20.6% in elderly adults. Further, working-age adults possessed suboptimal control on glycemia (median HbA1c: 7.0% vs. 6.8%, p < 0.001) and lipids (Low-density lipoprotein < 100 mg/dL: 46.4% vs. 63.5%, p < 0.001), but better blood pressure control (< 130/80 mmHg: 53.5% vs. 37.5%, p < 0.001) compared to the elderly, judging based on age-specific control targets. Prolonged diabetic duration didn't improve glycemic and composite factors control. SES like education and income impacted metabolic factors control and adults with higher SES were more likely to control well. Diabetic duration was a significant risk factor (OR = 4.006, 95%CI= (2.752,5.832), p < 0.001) while higher income (OR = 0.590, 95%CI= (0.421,0.826), p = 0.002) and educational level (OR = 0.637, 95%CI= (0.457,0.889), p = 0.008) were protective against DR. CONCLUSIONS: Working-age adults with diabetes demonstrate suboptimal metabolic profile control, especially glycemia and lipids. Additional efforts are needed to improve metabolic factor control and reduce DR risk, particularly for those with longer diabetes duration, less education, and lower incomes.

Helical polyisocyanide-based macroporous organic catalysts for asymmetric Michael addition with high efficiency and stereoselectivity.

Porous materials have attracted interest due to their high specific surface area and rich functionality. Immobilizing organocatalysts onto porous polymers not only boosts enantioselectivity but also improves the reaction rates. In this work, a series of porous polymers C-poly-3ms with rigid polyisocyanide-carrying secondary amine pendants as building blocks were successfully prepared. And the pore size and optical activity of C-poly-3ms can be controlled by the length of the polyisocyanide blocks due to their rigid and helical backbone. C-poly-3150 demonstrated a preferred left-handed helix with a θ 364 value of -8.21 × 103. The pore size and S BET of C-poly-3150 were 17.52 nm and 7.98 m2 g-1, respectively. The porous C-poly-3150 catalyzes the asymmetric Michael addition reaction efficiently and generates the target products in satisfactory yield and excellent enantioselectivity. For 6ab, an enantiomeric excess (ee) and a diastereomeric ratio (dr) up to 99% and 99/1 could be achieved, respectively. The recovered catalyst can be recycled at least 6 times in the asymmetric Michael addition reaction while maintaining activity and stereoselectivity.

Unlocking plant genetics with telomere-to-telomere genome assemblies.

Contiguous genome sequence assemblies will help us to realize the full potential of crop translational genomics. Recent advances in sequencing technologies, especially long-read sequencing strategies, have made it possible to construct gapless telomere-to-telomere (T2T) assemblies, thus offering novel insights into genome organization and function. Plant genomes pose unique challenges, such as a continuum of ancient to recent polyploidy and abundant highly similar and long repetitive elements. Owing to progress in sequencing approaches, for most crop plants, chromosome-scale reference genome assemblies are available, but T2T assembly construction remains challenging. Here we describe methods for haplotype-resolved, gapless T2T assembly construction in plants, including various crop species. We outline the impact of T2T assemblies in elucidating the roles of repetitive elements in gene regulation, as well as in pangenomics, functional genomics, genome-assisted breeding and targeted genome manipulation. In conjunction with sequence-enriched germplasm repositories, T2T assemblies thus hold great promise for basic and applied plant sciences.

TIN2 modulates FOXO1 mitochondrial shuttling to enhance oxidative stress-induced apoptosis in retinal pigment epithelium under hyperglycemia.

Progressive dysfunction of the retinal pigment epithelium (RPE) and the adjacent photoreceptor cells in the outer retina plays a pivotal role in the pathogenesis of diabetic retinopathy (DR). Here, we observed a marked increase in oxidative stress-induced apoptosis in parallel with higher expression of telomeric protein TIN2 in RPE cells under hyperglycemia in vivo and in vitro. Delving deeper, we confirm that high glucose-induced elevation of mitochondria-localized TIN2 compromises mitochondrial activity and weakens the intrinsic antioxidant defense, thereby leading to the activation of mitochondria-dependent apoptotic pathways. Mechanistically, mitochondrial TIN2 promotes the phosphorylation of FOXO1 and its relocation to the mitochondria. Such translocation of transcription factor FOXO1 not only promotes its binding to the D-loop region of mitochondrial DNA-resulting in the inhibition of mitochondrial respiration-but also hampers its availability to nuclear target DNA, thereby undermining the intrinsic antioxidant defense. Moreover, TIN2 knockdown effectively mitigates oxidative-induced apoptosis in diabetic mouse RPE by preserving mitochondrial homeostasis, which concurrently prevents secondary photoreceptor damage. Our study proposes the potential of TIN2 as a promising molecular target for therapeutic interventions for diabetic retinopathy, which emphasizes the potential significance of telomeric proteins in the regulation of metabolism and mitochondrial function. Created with BioRender ( https://www.biorender.com/ ).

A Novel High-Fidelity Simulation for Finishing Operations: Hybrid Image Mosaic and Wavelet Decomposition.

In finishing simulations, achieving accurate results can be challenging due to the minimal amount of material removal and the limited measurement range of surface micro-topography instruments. To overcome these limitations, a novel high-fidelity modeling method combining image mosaic and wavelet decomposition technologies is proposed in this paper. We achieve the stitching of narrow field and high pixel micro morphology images through four steps: image feature extraction, overlapped feature matching, feature fusion, and stitching effect evaluation. On this basis, the wavelet decomposition method is employed to separate detection signals based on their respective frequencies, allowing the establishment of a datum plane and a roughness surface. The point cloud model undergoes a transformation into a continuous geometric model via the Poisson reconstruction algorithm. In the case study, four sample images of an aluminum alloy sheet after barrel finishing were collected using the ZeGage Plus optical profiler. Each image has an actual size of 834.37 µm × 834.37 µm. Subsequently, a comparison was carried out between the physical and simulation experiments. The results clearly indicate that the proposed method has the potential to enhance the accuracy of the finishing simulation by over 30%. The error between the resulting model and the actual surface of the part can be controlled within 1 µm.

spatiAlign: an unsupervised contrastive learning model for data integration of spatially resolved transcriptomics.

BACKGROUND: Integrative analysis of spatially resolved transcriptomics datasets empowers a deeper understanding of complex biological systems. However, integrating multiple tissue sections presents challenges for batch effect removal, particularly when the sections are measured by various technologies or collected at different times. FINDINGS: We propose spatiAlign, an unsupervised contrastive learning model that employs the expression of all measured genes and the spatial location of cells, to integrate multiple tissue sections. It enables the joint downstream analysis of multiple datasets not only in low-dimensional embeddings but also in the reconstructed full expression space. CONCLUSIONS: In benchmarking analysis, spatiAlign outperforms state-of-the-art methods in learning joint and discriminative representations for tissue sections, each potentially characterized by complex batch effects or distinct biological characteristics. Furthermore, we demonstrate the benefits of spatiAlign for the integrative analysis of time-series brain sections, including spatial clustering, differential expression analysis, and particularly trajectory inference that requires a corrected gene expression matrix.

Obesity-enriched gut microbe degrades myo-inositol and promotes lipid absorption.

Numerous studies have reported critical roles for the gut microbiota in obesity. However, the specific microbes that causally contribute to obesity and the underlying mechanisms remain undetermined. Here, we conducted shotgun metagenomic sequencing in a Chinese cohort of 631 obese subjects and 374 normal-weight controls and identified a Megamonas-dominated, enterotype-like cluster enriched in obese subjects. Among this cohort, the presence of Megamonas and polygenic risk exhibited an additive impact on obesity. Megamonas rupellensis possessed genes for myo-inositol degradation, as demonstrated in vitro and in vivo, and the addition of myo-inositol effectively inhibited fatty acid absorption in intestinal organoids. Furthermore, mice colonized with M. rupellensis or E. coli heterologously expressing the myo-inositol-degrading iolG gene exhibited enhanced intestinal lipid absorption, thereby leading to obesity. Altogether, our findings uncover roles for M. rupellensis as a myo-inositol degrader that enhances lipid absorption and obesity, suggesting potential strategies for future obesity management.

Short-term effects of sunlight exposure on fundus blood flow perfusion in children: a randomised controlled trial.

AIM: To evaluate the short-term effects of different sunlight exposure on fundus blood flow perfusion (BFP) after near work. METHODS: In this parallel randomised controlled trial, 81 students aged 7-15 with spherical equivalent refraction between -2.00 and +3.00 diopters were randomly assigned to either a low-illuminance (4k lux) group (N=40) or high-illuminance (10k lux) (N=41). Following 1 hour indoor reading, participants had sunlight exposure matching their group's intensity for 15 minutes. BFPs in the superficial retina, deep retina and choroid were measured at four time points: pre-reading, post-reading, 5th-minute and 15th-minute sunlight exposure. RESULTS: Within the initial 5 minutes of sunlight exposure, the 10k lux group showed a tendency for decreased BFP, particularly in the choroid (superficial retina: -0.2, 95% CI -0.9 to 0.5; deep retina: -0.1, 95% CI -0.6 to 0.4; choroid: -0.4, 95% CI -0.8 to 0.0), while the 4k lux group exhibited an increase (superficial retina: 0.7, 95% CI 0.1 to 1.3; deep retina: 0.3, 95% CI -0.2 to 0.8; choroid: 0.1, 95% CI -0.2 to 0.5). From 5 to 15 minutes, BFP decreased in both groups. At the 5th-minute mark, the 10k lux group exhibited a greater decrease in choroid (10k -0.4 vs 4k 0.1, p=0.051). No significant difference was observed after 15 minutes of exposure. CONCLUSION: Higher illuminance sunlight exposure can restore fundus BFP more rapidly than lower; however, duration remains pivotal. To prevent myopia, continuous sunlight exposure for over 15 minutes is recommended to aid in reinstating the fundus BFP increased by near work. TRIAL REGISTRATION NUMBER: NCT05594732.

Analysis of Biodistribution and in vivo Toxicity of Varying Sized Polystyrene Micro and Nanoplastics in Mice.

Introduction: Studies have shown that microplastics (MPs) and nanoplastics (NPs) could accumulate in the human body and pose a potential threat to human health. The purpose of this study is to evaluate the biodistribution and toxicity of MPs/NPs with different particle sizes comprehensively and thoroughly. Methods: The purpose of this study was to investigate the biodistribution and in vivo toxicity of polystyrene (PS) MPs/NPs with different sizes (50 nm, 100 nm, and 500 nm). The BALB/c mice were given 100 µL of PS50, PS100 and PS500 at the dosage of 1 mg/kg BW or 10 mg/kg BW, respectively, by gavage once a day. After 28 consecutive days of treatment, the biodistribution of differently sized PS MPs/NPs was determined through cryosection fluorescence microscopy and fluorescent microplate reader analysis, and the subsequent effects of differently sized PS MPs/NPs on histopathology, hematology and blood biochemistry were also evaluated. Results: The results showed that the three different sizes of PS MPs/NPs were distributed in the organs of mice, mainly in the liver, spleen, and intestine. At the same time, the smaller the particle size, the more they accumulate in the body and more easily penetrate the tissue. During the whole observation period, no abnormal behavior and weight change were observed. The results of H&E staining showed that no severe histopathological abnormalities were observed in the main organs in the low-dose exposure group, while. Exposure of three sizes of PS MPs/NPs could cause some changes in hematological parameters or biochemical parameters related to heart, liver, and kidney function; meanwhile, there were size- and dose-dependencies. Conclusion: The biological distribution and toxicity of plastic particles in mice were more obvious with the decrease of particle size and the increase of concentration of plastic particles. Compared with MPs, NPs were easier to enter the tissues and produce changes in liver, kidney, and heart functions. Therefore, more attention should be paid to the toxicity of NPs.

Mapping the molecular landscape of Lotus japonicus nodule organogenesis through spatiotemporal transcriptomics.

Legumes acquire nitrogen-fixing ability by forming root nodules. Transferring this capability to more crops could reduce our reliance on nitrogen fertilizers, thereby decreasing environmental pollution and agricultural production costs. Nodule organogenesis is complex, and a comprehensive transcriptomic atlas is crucial for understanding the underlying molecular events. Here, we utilized spatial transcriptomics to investigate the development of nodules in the model legume, Lotus japonicus. Our investigation has identified the developmental trajectories of two critical regions within the nodule: the infection zone and peripheral tissues. We reveal the underlying biological processes and provide gene sets to achieve symbiosis and material exchange, two essential aspects of nodulation. Among the candidate regulatory genes, we illustrate that LjNLP3, a transcription factor belonging to the NIN-LIKE PROTEIN family, orchestrates the transition of nodules from the differentiation to maturation. In summary, our research advances our understanding of nodule organogenesis and provides valuable data for developing symbiotic nitrogen-fixing crops.

A single-cell transcriptome atlas of human euploid and aneuploid blastocysts.

Aneuploidy is frequently detected in early human embryos as a major cause of early pregnancy failure. However, how aneuploidy affects cellular function remains elusive. Here, we profiled the transcriptomes of 14,908 single cells from 203 human euploid and aneuploid blastocysts involving autosomal and sex chromosomes. Nearly all of the blastocysts contained four lineages. In aneuploid chromosomes, 19.5% ± 1.2% of the expressed genes showed a dosage effect, and 90 dosage-sensitive domains were identified. Aneuploidy leads to prevalent genome-wide transcriptome alterations. Common effects, including apoptosis, were identified, especially in monosomies, partially explaining the lower cell numbers in autosomal monosomies. We further identified lineage-specific effects causing unstable epiblast development in aneuploidies, which was accompanied by the downregulation of TGF-ß and FGF signaling, which resulted in insufficient trophectoderm maturation. Our work provides crucial insights into the molecular basis of human aneuploid blastocysts and may shed light on the cellular interaction during blastocyst development.

Chiral photon blockade in the spinning Kerr resonator.

We propose how to achieve chiral photon blockade by spinning a nonlinear optical resonator. We show that by driving such a device at a fixed direction, completely different quantum effects can emerge for the counter-propagating optical modes, due to the spinning-induced breaking of time-reversal symmetry, which otherwise is unattainable for the same device in the static regime. Also, we find that in comparison with the static case, robust non-classical correlations against random backscattering losses can be achieved for such a quantum chiral system. Our work, extending previous works on the spontaneous breaking of optical chiral symmetry from the classical to purely quantum regimes, can stimulate more efforts towards making and utilizing various chiral quantum effects, including applications for chiral quantum networks or noise-tolerant quantum sensors.

Divergent age-associated and metabolism-associated gut microbiome signatures modulate cardiovascular disease risk.

Insight into associations between the gut microbiome with metabolism and aging is crucial for tailoring interventions to promote healthy longevity. In a discovery cohort of 10,207 individuals aged 40-93 years, we used 21 metabolic parameters to classify individuals into five clusters, termed metabolic multimorbidity clusters (MCs), that represent different metabolic subphenotypes. Compared to the cluster classified as metabolically healthy (MC1), clusters classified as 'obesity-related mixed' (MC4) and 'hyperglycemia' (MC5) exhibited an increased 11.1-year cardiovascular disease (CVD) risk by 75% (multivariable-adjusted hazard ratio (HR): 1.75, 95% confidence interval (CI): 1.43-2.14) and by 117% (2.17, 1.72-2.74), respectively. These associations were replicated in a second cohort of 9,061 individuals with a 10.0-year follow-up. Based on analysis of 4,491 shotgun fecal metagenomes from the discovery cohort, we found that gut microbial composition was associated with both MCs and age. Next, using 55 age-specific microbial species to capture biological age, we developed a gut microbial age (MA) metric, which was validated in four external cohorts comprising 4,425 metagenomic samples. Among individuals aged 60 years or older, the increased CVD risk associated with MC4 or MC5, as compared to MC1, MC2 or MC3, was exacerbated in individuals with high MA but diminished in individuals with low MA, independent of age, sex and other lifestyle and dietary factors. This pattern, in which younger MA appears to counteract the CVD risk attributable to metabolic dysfunction, implies a modulating role of MA in cardiovascular health for metabolically unhealthy older people.