Multi-omics analyses provide insights into the genomic basis of differentiation among four sweet osmanthus groups.

Sweet osmanthus (Osmanthus fragrans) is famous in China for its flowers and contains four groups: Albus, Luteus, Aurantiacus, and Asiaticus. Understanding the relationships among these groups and the genetic mechanisms of flower color and aroma biosynthesis are of tremendous interest. In this study, we sequenced representative varieties from two of the four sweet osmanthus groups. Multi-omic and phylogenetic analyses of varieties from each of the four groups showed that Asiaticus split first within the species, followed by Aurantiacus and the sister groups Albus and Luteus. We show that the difference in flower color between Aurantiacus and the other three groups was caused by a 4-bp deletion in the promoter region of carotenoid cleavage dioxygenase 4 (OfCCD4) that leads to expression decrease. In addition, we identified 44 gene pairs exhibiting significant structural differences between the multi-seasonal flowering variety 'Rixianggui' in the Asiaticus group and other autumn flowering varieties. Through correlation analysis between intermediate products of aromatic components and gene expression, we identified eight genes associated with the linalool, α- and ß-ionone biosynthesis pathways. Overall, our study offers valuable genetic resources for sweet osmanthus, while also providing genetic clues for improving the flower color and multi-season flowering of osmanthus and other flowers.

A Phase 3, Randomized, Controlled Trial Evaluating the Efficacy and Safety of Ropeginterferon Alfa-2b in Patients with Moderate COVID-19.

INTRODUCTION: Ropeginterferon alfa-2b is a novel mono-pegylated proline-interferon. This clinical study aimed to evaluate its antiviral efficacy of ropeginterferon alfa-2b against SARS-CoV-2 infection. METHODS: This is a multicenter, randomized, open-label study. Adult patients with confirmed SARS-CoV-2 infection with initial cycle threshold (Ct) value < 30 and symptom onset within 4 days were enrolled. Eligible patients were randomized in a 2:1 ratio to receive a single 250-µg dose of ropeginterferon alfa-2b subcutaneously plus standard of care (SOC) or to receive SOC alone. The primary endpoint was the proportion of patients with a negative RT-PCR result for SARS-CoV-2 or discharged from the hospital before Day 8. Change in clinical status based on the World Health Organization (WHO) clinical progression scale and pulmonary infiltrations through chest radiograph were also evaluated. RESULTS: A total of 132 patients were enrolled and treated with study medication. Higher percentages of patients who achieved Ct ≥ 30 or were discharged from the hospital were observed on Day 8 and every other time point of assessment, i.e., Days 5, 11, 15, and 22, in the ropeginterferon alfa-2b group compared to the SOC alone group. However, the difference was statistically significant on Day 11 but not on Day 8. The primary endpoint was not met. The ropeginterferon alfa-2b group showed a higher improvement rate in lung infiltration on Day 5 (27.6% vs. 0.0%, p = 0.0087) and a higher improvement rate in WHO clinical progression scores on Day 8 (69.4% vs. 35.3%, p = 0.03) than those in the SOC group. No ropeginterferon alfa-2b-related serious adverse event was observed. CONCLUSION: Our data show that ropeginterferon alfa-2b with SOC shortened the duration of SARS-CoV-2 shedding compared with SOC alone. In addition, ropeginterferon alfa-2b as an additional therapy could be beneficial by improving lung infiltration.

Highly intense NIR emissive Cu4Pt2 bimetallic clusters featuring Pt(i)-Cu4-Pt(i) sandwich kernel.

Metal nanoclusters (NCs) capable of near-infrared (NIR) photoluminescence (PL) are gaining increasing interest for their potential applications in bioimaging, cell labelling, and phototherapy. However, the limited quantum yield (QY) of NIR emission in metal NCs, especially those emitting beyond 800 nm, hinders their widespread applications. Herein, we present a bright NIR luminescence (PLQY up to 36.7%, ∼830 nm) bimetallic Cu4Pt2 NC, [Cu4Pt2(MeO-C6H5-C[triple bond, length as m-dash]C)4(dppy)4]2+ (dppy = diphenyl-2-pyridylphosphine), with a high yield (up to 67%). Furthermore, by modifying the electronic effects of R in RC[triple bond, length as m-dash]C- (R = MeO-C6H5, F-C6H5, CF3-C6H5, Nap, and Biph), we can effectively modulate phosphorescence properties, including the PLQY, emission wavelength, and excited state decay lifetime. Experimental and computational studies both demonstrate that in addition to the electron effects of substituents, ligand modification enhances luminescence intensity by suppressing non-radiation transitions through intramolecular interactions. Simultaneously, it allows the adjustment of emitting wavelengths by tuning the energy gaps and first excited triplet states through intermolecular interactions of ligand substituents. This study provides a foundation for rational design of the atomic-structures of alloy metal NCs to enhance their PLQY and tailor the PL wavelength of NIR emission.

METTL3 Promotes Osteosarcoma Metastasis via an m6A-dependent Epigenetic Activity of CBX4.

BACKGROUND: Osteosarcoma cells are prone to metastasis, and the mechanism of N6-methyladenosine (m6A) methylation modification in this process is still unclear. Methylation modification of m6A plays an important role in the development of osteosarcoma, which is mainly due to abnormal expression of enzymes related to methylation modification of m6A, which in turn leads to changes in the methylation level of downstream target genes messenger RNA (mRNA) leading to tumor development. METHODS: We analyzed the expression levels of m6A methylation modification-related enzyme genes in GSE12865 whole-genome sequencing data. And we used shRNA (short hairpin RNA) lentiviral interference to interfere with METTL3 (Methyltransferase 3) expression in osteosarcoma cells. We studied the cytological function of METTL3 by Cell Counting Kit-8 (CCK8), flow cytometry, migration and other experiments, and the molecular mechanism of METTL3 by RIP (RNA binding protein immunoprecipitation), Western blot and other experiments. RESULTS: We found that METTL3 is abnormally highly expressed in osteosarcoma and interferes with METTL3 expression in osteosarcoma cells to inhibit metastasis, proliferation, and apoptosis of osteosarcoma cells. We subsequently found that METTL3 binds to the mRNA of CBX4 (chromobox homolog 4), a very important regulatory protein in osteosarcoma metastasis, and METTL3 regulates the mRNA and protein expression of CBX4. Further studies revealed that METTL3 inhibited metastasis of osteosarcoma cells by regulating CBX4. METTL3 has been found to be involved in osteosarcoma cells metastasis by CBX4 affecting the protein expression of matrix metalloproteinase 2 (MMP2), MMP9, E-Cadherin and N-Cadherin associated with osteosarcoma cells metastasis. CONCLUSIONS: These results suggest that the combined action of METTL3 and CBX4 plays an important role in the regulation of metastasis of osteosarcoma, and therefore, the METTL3-CBX4 axis pathway may be a new potential therapeutic target for osteosarcoma.

Aberrant degree centrality profiles during rumination in major depressive disorder.

Rumination is closely linked to the onset and maintenance of major depressive disorder (MDD). Prior neuroimaging studies have identified the association between self-reported rumination trait and the functional coupling among a network of brain regions using resting-state functional magnetic resonance imaging (MRI). However, little is known about the underlying neural circuitry mechanism during active rumination in MDD. Degree centrality (DC) is a simple metric to denote network integration, which is critical for higher-order psychological processes such as rumination. During an MRI scan, individuals with MDD (N = 45) and healthy controls (HC, N = 46) completed a rumination state task. We examined the interaction effect between the group (MDD vs. HC) and condition (rumination vs. distraction) on vertex-wise DC. We further characterized the identified brain region's functional involvement with Neurosynth and BrainMap. Network-wise seed-based functional connectivity (FC) analysis was also conducted for the identified region of interest. Finally, exploratory correlation analysis was conducted between the identified region of interest's network FCs and self-reported in-scanner affect levels. We found that a left superior frontal gyrus (SFG) region, generally overlapped with the frontal eye field, showed a significant interaction effect. Further analysis revealed its involvement with executive functions. FCs between this region, the frontoparietal, and the dorsal attention network (DAN) also showed significant interaction effects. Furthermore, its FC to DAN during distraction showed a marginally significant negative association with in-scanner affect level at the baseline. Our results implicated an essential role of the left SFG in the rumination's underlying neural circuitry mechanism in MDD and provided novel evidence for the conceptualization of rumination in terms of impaired executive control.

A new mechanism of flowering regulation by the competition of isoforms in Osmanthus fragrans.

The regulation of flowering time is typically governed by transcription factors or epigenetic modifications. Transcript isoforms can play important roles in flowering regulation. Recently, transcript isoforms were discovered in the key genes, OfAP1 and OfTFL1, of the flowering regulatory network in Osmanthus fragrans. OfAP1-b generates a full-length isoform of OfAP1-b1 as well as an isoform of OfAP1-b2 that lacks the C-terminal domain. Although OfAP1-b2 does not possess an activation domain, it has a complete K domain that allows it to form heterodimers. OfAP1-b2 competes with OfAP1-b1 by binding with OfAGL24 to create non-functional and functional heterodimers. As a result, OfAP1-b1 promotes flowering while OfAP1-b2 delays flowering. OfTFL1 produces two isoforms located in different areas: OfTFL1-1 in the cytoplasm and OfTFL1-2 in the nucleus. When combined with OfFD, OfTFL1-1 does not enter the nucleus to repress AP1 expression, leading to early flowering. Conversely, when combined with OfFD, OfTFL1-2 enters the nucleus to repress AP1 expression, resulting in later flowering. Tissue-specific expression and functional conservation testing of OfAP1 and OfTFL1 support the new model's effectiveness in regulating flowering. Overall, this study provides new insights into regulating flowering time by the competition of isoforms.

Random Telegraph Noise Degradation Caused by Hot Carrier Injection in a 0.8 µm-Pitch 8.3Mpixel Stacked CMOS Image Sensor.

In this work, the degradation of the random telegraph noise (RTN) and the threshold voltage (Vt) shift of an 8.3Mpixel stacked CMOS image sensor (CIS) under hot carrier injection (HCI) stress are investigated. We report for the first time the significant statistical differences between these two device aging phenomena. The Vt shift is relatively uniform among all the devices and gradually evolves over time. By contrast, the RTN degradation is evidently abrupt and random in nature and only happens to a small percentage of devices. The generation of new RTN traps by HCI during times of stress is demonstrated both statistically and on the individual device level. An improved method is developed to identify RTN devices with degenerate amplitude histograms.

The interface microenvironment mediates the emission of a semiconductor nanocluster via surface-dopant-involving direct charge transfer.

The interface microenvironment of doped quantum dots (QDs) is crucial in optimizing the properties associated with the photogenerated excitons. However, the imprecision of QDs' surface structures and compositions impedes a thorough understanding of the modulation mechanism caused by the complex interface microenvironment, particularly distinguishing the contribution of surface dopants from inner ones. Herein, we investigated interface-mediated emission using a unique model of an atomically precise chalcogenide semiconductor nanocluster containing uniform near-surface Mn2+ dopants. Significantly, we discovered that Mn2+ ions can directly transfer charges with hydrogen-bonding-bound electron-rich alkylamines with matched molecular configurations and electronic structures at the interface. This work provides a new pathway, the use of atomically precise nanoclusters, for analyzing and enhancing the interface-dependent properties of various doped QDs, including chalcogenides and perovskites.

Phylogenomics insights into gene evolution, rapid species diversification, and morphological innovation of the apple tribe (Maleae, Rosaceae).

Maleae is one of the most widespread tribes of Rosaceae and includes several important fruit crops and ornamental plants. We used nuclear genes from 62 transcriptomes/genomes, including 26 newly generated transcriptomes, to reconstruct a well-supported phylogeny and study the evolution of fruit and leaf morphology and the possible effect of whole genome duplication (WGD). Our phylogeny recovered 11 well-supported clades and supported the monophyly of most genera (except Malus, Sorbus, and Pourthiaea) with at least two sampled species. A WGD was located to the most recent common ancestor (MRCA) of Maleae and dated to c. 54 million years ago (Ma) near the Early Eocene Climatic Optimum, supporting Gillenieae (x = 9) being a parental lineage of Maleae (x = 17) and including duplicate regulatory genes related to the origin of the fleshy pome fruit. Whole genome duplication-derived paralogs that are retained in specific lineages but lost in others are predicted to function in development, metabolism, and other processes. An upshift of diversification and innovations of fruit and leaf morphologies occurred at the MRCA of the Malinae subtribe, coinciding with the Eocene-Oligocene transition (c. 34 Ma), following a lag from the time of the WGD event. Our results provide new insights into the Maleae phylogeny, its rapid diversification, and morphological and molecular evolution.

Alkynyl-Protected Bimetallic Nanoclusters with a Hybrid Mackay Icosahedral Ag42 Cu12 Cl Kernel and an Octahedral Ag22 Cu12 Kernel.

A facile strategy that directly reduces alkynyl-silver precursors and copper salts for the synthesis of bimetallic nanoclusters using the weak reducing agent Ph2 SiH2 is demonstrated. Two alkynyl-protected concentric-shell nanoclusters, (Ph4 P)2 [Ag22 Cu12 (C≡CR)28 ] and (Ph4 P)3 [Ag42 Cu12 Cl(C≡CR)36 ] (Ag22 Cu12 and Ag42 Cu12 Cl, R=bis(trifluoromethyl)phenyl), were successfully obtained and characterized by single-crystal X-ray diffraction and electro-spray ionization mass spectrometry. For the first time, a hybrid 55-atom two-shell Mackay icosahedron was found in Ag42 Cu12 Cl, which is icosahedral M54 Cl instead of M55 . The incorporation of a chloride in the metal icosahedron contributes to the stability of the cluster from both electronic and geometric aspects. Alkynyl ligands show various binding-modes including linear "RC≡C-Cu-C≡CR" staple motifs.

Ghrelin promotes cardiomyocyte differentiation of adipose tissue­derived mesenchymal stem cells by DDX17­mediated regulation of the SFRP4/Wnt/ß­catenin axis.

Adipose tissue­derived mesenchymal stem cells (ADMSCs) differentiate into cardiomyocytes and may be an ideal cell source for myocardial regenerative medicine. Ghrelin is a gastric­secreted peptide hormone involved in the multilineage differentiation of MSCs. To the best of our knowledge, however, the role and potential downstream regulatory mechanism of ghrelin in cardiomyocyte differentiation of ADMSCs is still unknown. The mRNA and protein levels were measured by reverse transcription­quantitative PCR and western blotting. Immunofluorescence staining was used to show the expression and cellular localization of cardiomyocyte markers and ß­catenin. RNA sequencing was used to explore the differentially expressed genes (DEGs) that regulated by ghrelin. The present study found that ghrelin promoted cardiomyocyte differentiation of ADMSCs in a concentration­dependent manner, as shown by increased levels of cardiomyocyte markers GATA binding protein 4, α­myosin heavy chain (α­MHC), ISL LIM homeobox 1, NK2 homeobox 5 and troponin T2, cardiac type. Ghrelin increased ß­catenin accumulation in nucleus and decreased the protein expression of secreted frizzled­related protein 4 (SFRP4), an inhibitor of Wnt signaling. RNA sequencing was used to determine the DEGs regulated by ghrelin. Functional enrichment showed that DEGs were more enriched in cardiomyocyte differentiation­associated terms and Wnt pathways. Dead­box helicase 17 (DDX17), an upregulated DEG, showed enhanced mRNA and protein expression levels following ghrelin addition. Overexpression of DDX17 promoted protein expression of cardiac­specific markers and ß­catenin and enhanced the fluorescence intensity of α­MHC and ß­catenin. DDX17 upregulation inhibited protein expression of SFRP4. Rescue assay confirmed that the addition of SFRP4 partially reversed ghrelin­enhanced protein levels of cardiac­specific markers and the fluorescence intensity of α­MHC. In conclusion, ghrelin promoted cardiomyocyte differentiation of ADMSCs by DDX17­mediated regulation of the SFRP4/Wnt/ß­catenin axis.

Panax notoginseng alleviates oxidative stress through miRNA regulations based on systems biology approach.

BACKGROUND: Herbal medicine Sanqi (SQ), the dried root or stem of Panax notoginseng (PNS), has been reported to have anti-diabetic and anti-obesity effects and is usually administered as a decoction for Chinese medicine. Alternative to utilizing PNS pure compound for treatment, we are motivated to propose an unconventional scheme to investigate the functions of PNS mixture. However, studies providing a detailed overview of the transcriptomics-based signaling network in response to PNS are seldom available. METHODS: To explore the reasoning of PNS in treating metabolic disorders such as insulin resistance, we implemented a systems biology-based approach with RNA sequencing (RNA-seq) and miRNA sequencing data to elucidate key pathways, genes and miRNAs involved. RESULTS: Functional enrichment analysis revealed PNS up-regulating oxidative stress-related pathways and down-regulating insulin and fatty acid metabolism. Superoxide dismutase 1 (SOD1), peroxiredoxin 1 (PRDX1), heme oxygenase-1 (Hmox1) and glutamate cysteine ligase (GCLc) mRNA and protein levels, as well as related miRNA levels, were measured in PNS treated rat pancreatic ß cells (INS-1). PNS treatment up-regulated Hmox1, SOD1 and GCLc expression while down-regulating miR-24-3p and miR-139-5p to suppress oxidative stress. Furthermore, we verified the novel interactions between miR-139-5p and miR-24-3p with GCLc and SOD1. CONCLUSION: This work has demonstrated the mechanism of how PNS regulates cellular molecules in metabolic disorders. Therefore, combining omics data with a systems biology strategy could be a practical means to explore the potential function and molecular mechanisms of Chinese herbal medicine in the treatment of metabolic disorders.

Ellagic acid induces apoptosis and autophagy in colon cancer through the AMPK/mTOR pathway.

Ellagic acid (EA), found in fruits and foods, has been shown to be effective in the treatment of breast, colon and bladder cancer. However, due to the complexity of colon cancer, the therapeutic mechanism of EA for colon cancer is still unclear. Cell Counting Kit-8 (CCK-8) assay were employed to investigate the cell proliferation. Western blotting and flow cytometry assays were utilized to investigate apoptosis and autophagy in CRC cells (HCT116), respectively. Moreover, western blotting and luciferase reporter assays were evaluated the effect of EA on AMPK/mTOR pathway. Through flow cytometry analysis, EA could promote the apoptosis of HCT116 cells. In addition, EA can reduce the phosphorylation of mTOR, promoted phosphorylation of AMPK, and induced autophagy in HCT116 cells. Also, Dorsomorphin pretreatment can reduce the expression of autophagy protein, which indicates that EA induces autophagy through AMPK/mTOR pathway. These results suggest that EA inhibits the growth of colon cancer through AMPK/mTOR pathway and induces apoptosis and protective autophagy.

Meta-Prediction of Coronary Artery Disease Risk.

Coronary artery disease (CAD) remains the leading cause of mortality and morbidity worldwide. Recent advances in large-scale genome-wide association studies have highlighted the potential of genetic risk, captured as polygenic risk scores (PRS), in clinical prevention. However, the current clinical utility of PRS models is limited to identifying high-risk populations based on the top percentiles of genetic susceptibility. While some studies have attempted integrative prediction using genetic and non-genetic factors, many of these studies have been cross-sectional and focused solely on risk stratification. Our primary objective in this study was to integrate unmodifiable (age / genetics) and modifiable (clinical / biometric) risk factors into a prospective prediction framework which also produces actionable and personalized risk estimates for the purpose of CAD prevention in a heterogenous adult population. Thus, we present an integrative, omnigenic, meta-prediction framework that effectively captures CAD risk subgroups, primarily distinguished by degree and nature of genetic risk, with distinct risk reduction profiles predicted from standard clinical interventions. Initial model development considered ~ 2,000 predictive features, including demographic data, lifestyle factors, physical measurements, laboratory tests, medication usage, diagnoses, and genetics. To power our meta-prediction approach, we stratified the UK Biobank into two primary cohorts: 1) a prevalent CAD cohort used to train baseline and prospective predictive models for contributing risk factors and diagnoses, and 2) an incident CAD cohort used to train the final CAD incident risk prediction model. The resultant 10-year incident CAD risk model is composed of 35 derived meta-features from models trained on the prevalent risk cohort, most of which are predicted baseline diagnoses with multiple embedded PRSs. This model achieved an AUC of 0.81 and macro-averaged F1-score of 0.65, outperforming standard clinical scores and prior integrative models. We further demonstrate that individualized risk reduction profiles can be derived from this model, with genetic risk mediating the degree of risk reduction achieved by standard clinical interventions.

X-ray photochromism of chalcogenide frameworks linked with metal-amine chelates.

Reported here are two X-ray photochromic metal chalcogenide frameworks, which consist of tetrahedral clusters that are linked by transition-metal amine chelates. They have similar structures, but with different organic amine species, and they exhibit different coloration behavior. The photoinduced electron transfer from the metal chalcogenide clusters to the zinc amine chelates is a key point in accounting for their photochromism. Interestingly, a high-contrast (up to 12.4 times) enhancement of the optoelectronic response is obtained for the title compounds after they are treated by X-ray irradiation.

MAGE-A3 regulates tumor stemness in gastric cancer through the PI3K/AKT pathway.

Gastric cancer remains a malignant disease of the digestive tract with high mortality and morbidity worldwide. However, due to its complex pathological mechanisms and lack of effective clinical therapies, the survival rate of patients after receiving treatment is not satisfactory. A increasing number of studies have focused on cancer stem cells and their regulatory properties. In this study, we first constructed a co-expression network based on the WGCNA algorithm to identify modules with different degrees of association with tumor stemness indices. After selecting the most positively correlated modules of the stemness index, we performed a consensus clustering analysis on gastric cancer samples and constructed the co-expression network again. We then selected the modules of interest and applied univariate COX regression analysis to the genes in this module for preliminary screening. The results of the screening were then used in LASSO regression analysis to construct a risk prognostic model and subsequently a sixteen-gene model was obtained. Finally, after verifying the accuracy of the module and screening for risk genes, we identified MAGE-A3 as the final study subject. We then performed in vivo and in vitro experiments to verify its effect on tumor stemness and tumour proliferation. Our data supports that MAGE-A3 is a tumor stemness regulator and a potent prognostic biomarker which can help the prediction and treatment of gastric cancer patients.

Face-Centered Cubic Silver Nanoclusters Consolidated with Tetradentate Formamidinate Ligands.

Growing attention has been paid to nanoclusters with face-centered cubic (fcc) metal kernels, due to its structural similarity to bulk metals. We demonstrate that the use of tetradentate formamidinate ligands facilitate the construction of two fcc silver nanoclusters: [Ag52(5-F-dpf)16Cl4](SbF6)2 (Ag52, 5-F-Hdpf = N,N'-di(5-fluoro-2-pyridinyl)formamidine) and [Ag53(5-Me-dpf)18](NO3)5 (Ag53, 5-Me-Hdpf = N,N'-di(5-methyl-2-pyridinyl)formamidine). Single-crystal X-ray structural analysis revealed that the silver atoms in both clusters are in a layer-by-layer arrangement, which can be viewed as a portion of the fcc packing of silver. The nitrogen donors of amidinate ligands selectively passivate the {111} facets. All silver atoms are involved in the fcc packing, that is, no staple motifs are observed due to the linear arrangement of the four N donors of the dpf ligands. The characteristic optical absorption bands of Ag52 and Ag53 have been studied with a time-dependent density functional theory. This work provides a facile access to assembling atomically precise fcc-type nanoclusters and shows the prospect of amidinates as protecting ligands in synthesizing metal nanoclusters.

Genetically-informed prediction of short-term Parkinson's disease progression.

Parkinson's disease (PD) treatments modify disease symptoms but have not been shown to slow progression, characterized by gradual and varied motor and non-motor changes overtime. Variation in PD progression hampers clinical research, resulting in long and expensive clinical trials prone to failure. Development of models for short-term PD progression prediction could be useful for shortening the time required to detect disease-modifying drug effects in clinical studies. PD progressors were defined by an increase in MDS-UPDRS scores at 12-, 24-, and 36-months post-baseline. Using only baseline features, PD progression was separately predicted across all timepoints and MDS-UPDRS subparts in independent, optimized, XGBoost models. These predictions plus baseline features were combined into a meta-predictor for 12-month MDS UPDRS Total progression. Data from the Parkinson's Progression Markers Initiative (PPMI) were used for training with independent testing on the Parkinson's Disease Biomarkers Program (PDBP) cohort. 12-month PD total progression was predicted with an F-measure 0.77, ROC AUC of 0.77, and PR AUC of 0.76 when tested on a hold-out PPMI set. When tested on PDBP we achieve a F-measure 0.75, ROC AUC of 0.74, and PR AUC of 0.73. Exclusion of genetic predictors led to the greatest loss in predictive accuracy; ROC AUC of 0.66, PR AUC of 0.66-0.68 for both PPMI and PDBP testing. Short-term PD progression can be predicted with a combination of survey-based, neuroimaging, physician examination, and genetic predictors. Dissection of the interplay between genetic risk, motor symptoms, non-motor symptoms, and longer-term expected rates of progression enable generalizable predictions.

Rapid, Reference-Free human genotype imputation with denoising autoencoders.

Genotype imputation is a foundational tool for population genetics. Standard statistical imputation approaches rely on the co-location of large whole-genome sequencing-based reference panels, powerful computing environments, and potentially sensitive genetic study data. This results in computational resource and privacy-risk barriers to access to cutting-edge imputation techniques. Moreover, the accuracy of current statistical approaches is known to degrade in regions of low and complex linkage disequilibrium. Artificial neural network-based imputation approaches may overcome these limitations by encoding complex genotype relationships in easily portable inference models. Here, we demonstrate an autoencoder-based approach for genotype imputation, using a large, commonly used reference panel, and spanning the entirety of human chromosome 22. Our autoencoder-based genotype imputation strategy achieved superior imputation accuracy across the allele-frequency spectrum and across genomes of diverse ancestry, while delivering at least fourfold faster inference run time relative to standard imputation tools.

Ultrastable Anti-Acid "Shield" in Layered Silver Coordination Polymers.

Surface passivation technology provides noble-metal materials with limited chemical stability, especially under highly acidic condition. To design effective strategy to enhance stability of noble-metal particles, an understanding of their surface anticorrosion mechanism at the atomic level is desirable by using two-dimensional (2D) noble-metal coordination polymer (CP) as an ideal model for their interfacial region. With the protection of 2-thiobenzimidazole (TBI), we isolated two Ag-based 2D CPs, {Ag14 (TBI)12 X2 }n (S-X, where S denotes sheet and X=Cl or Br). These compounds exhibited excellent chemical stability upon immersion in various common solvents, boiling water, boiling ethanol, 10 % hydrogen peroxide, concentrated acid (12 M HCl), and concentrated alkali (19 M NaOH). Systematic characterization and DFT analyses demonstrate that the superior stability of S-X was attributed to the hydrophobic organic shell and dynamic proton buffer layer acting as a double protective "shield".