Hyposalinity stress reduces mussel byssus secretion but does not cause detachment.

Environmental stressors such as salinity fluctuations can significantly impact the ecological dynamics of mussel beds. The present study evaluated the influence of hyposalinity stress on the detachment and survival of attached mussels by simulating a mussel farming model in a laboratory setting. Byssus production and mechanical properties of thread in response to varying salinity levels were assessed, and histological sections of the mussel foot were analyzed to identify the changes in the byssus secretory gland area. The results showed that hyposalinity stress (20 and 15 psu) led to a significant decrease in mussel byssus secretion, delayed initiation of new byssus production, and reduced plaque adhesion strength and breaking force of byssal threads compared to the control (30 psu) (p < 0.05). The complete suppression of byssal thread secretion in mussels under salinity conditions of 10 and 5 psu, leading to lethality, indicates the presence of a blockade in byssus secretion when mussels are subjected to significant physiological stressors. Histological analysis further demonstrated a decrease in the percentage of foot secretory gland areas in mussels exposed to low salinities. However, contrary to expectations, the study found that mussels did not exhibit marked detachment from ropes in response to the reduced salinity levels during one week of exposure. Hyposalinity stress exposure reduced the byssal secretion capacity and the mechanical properties of threads, which could be a cause for the detachment of suspension-cultured mussels. These results highlight the vulnerability of mussels to hyposalinity stress, which significantly affects their byssus mechanical performance.

Accelerated somatic mutation calling for whole-genome and whole-exome sequencing data from heterogenous tumor samples.

Accurate detection of somatic mutations in DNA sequencing data is a fundamental prerequisite for cancer research. Previous analytical challenge was overcome by consensus mutation calling from four to five popular callers. This, however, increases the already nontrivial computing time from individual callers. Here, we launch MuSE 2, powered by multi-step parallelization and efficient memory allocation, to resolve the computing time bottleneck. MuSE 2 speeds up 50 times than MuSE 1 and 8-80 times than other popular callers. Our benchmark study suggests combining MuSE 2 and the recently accelerated Strelka2 achieves high efficiency and accuracy in analyzing large cancer genomic datasets.

Bernard-Soulier syndrome caused by two novel heterozygous GP1BA gene mutations: a case report and literature review.

BACKGROUND: Bernard-Soulier syndrome (BSS) is a rare inherited macrothrombocytopenia, usually autosomal recessive, which is characterized by prolonged bleeding, thrombocytopenia, and abnormally large platelets. METHODS: For more than 6 years, we misdiagnosed a patient with BSS without an obvious bleeding tendency as having idiopathic thrombocytopenia purpura (ITP), prior to obtaining a genetic analysis. On admission, routine hematology showed a platelet count of 30 × 109/L and mean platelet volume (MPV) of 14.0 fL. RESULTS: Whole-exome sequencing revealed two likely pathogenic heterozygous mutations (c.95_101del and c.1012del) in GP1BA. Flow cytometry analysis of platelet membrane glycoproteins indicated that the expression of GP1b was 0.28% of the normal level. Platelet aggregation tests indicated that platelet aggregation was inhibited by ristocetin- (1.7%), ADP- (14.5%), and arachidonic acid- (5.6%) induced platelet aggregation. A literature review identified reports on 53 mutations in the GP1BA gene in 253 patients, 29 mutations in the GP1BB gene in 90 patients, and 32 mutations in the GP9 gene in 114 patients. CONCLUSION: This case report describes two novel gene mutation sites that have not been reported previously, enriching understanding of the GP1BA mutation spectrum.

Transcranial direct current stimulation combined with swimming exercise improves the learning and memory abilities of vascular dementia rats by regulating microglia through miR-223-3p/PRMT8.

BACKGROUND: Vascular dementia (VD) is the second most common type of dementia worldwide. Previous studies have proven that transcranial direct current stimulation (tDCS) has potential applications in relieving cognitive impairment in VD animal models. The purpose of this study was to probe the mechanism by which tDCS combined with swimming exercise improves the learning and memory abilities of VD model rats. METHOD: The VD rat model was induced using the permanent bilateral common carotid artery occlusion (2-VO) method; tDCS was applied to the rats and then they took part in swimming exercises. Rat memory, platform crossing time, and platform crossing frequency were analyzed via a water maze experiment. Nerve damage in the cortex and hippocampal CA1 area of the rats was observed using Nissl staining. Western blotting, immunohistochemistry, immunofluorescence staining and reverse transcription quantitative polymerase chain reaction (RT - qPCR) were used to determine the expression of related proteins and genes. The levels of oxidative stress were detected by kits. RESULTS: We demonstrated that VD model rats treated with tDCS combined with swimming exercise exhibited significant improvement in memory, and VD model rats exhibited significantly reduced neuronal loss in the hippocampus, and reduced microglial activation and M1 polarization. tDCS combined with swimming exercise protects VD model rats from oxidative stress through the miR-223-3p/protein arginine methyltransferase 8 (PRMT8) axis and inhibits the activation of the TLR4/NF-κB signaling pathway. CONCLUSION: Our results suggest that tDCS combined with swimming exercise improved the learning and memory ability of VD model rats by regulating the expression of PRMT8 through miR-223-3p to affect microglial activation and M1 polarization.

Multifunctional polypeptide-based hydrogel bio-adhesives with pro-healing activities and their working principles.

Wound healing is a complex physiological process involving hemostasis, inflammation, proliferation, and tissue remodeling. Therefore, there is an urgent need for suitable wound dressings for effective and systematical wound management. Polypeptide-based hydrogel bio-adhesives offer unique advantages and are ideal candidates. However, comprehensive reviews on polypeptide-based hydrogel bio-adhesives for wound healing are still lacking. In this review, the physiological mechanisms and evaluation parameters of wound healing were first described in detail. Then, the working principles of hydrogel bio-adhesives were summarized. Recent advances made in multifunctional polypeptide-based hydrogel bio-adhesives involving gelatin, silk fibroin, fibrin, keratin, poly-γ-glutamic acid, ɛ-poly-lysine, serum albumin, and elastin with pro-healing activities in wound healing and tissue repair were reviewed. Finally, the current status, challenges, developments, and future trends of polypeptide-based hydrogel bio-adhesives were discussed, hoping that further developments would be stimulated to meet the growing needs of their clinical applications.

Validating Risk Prediction Models for Multiple Primaries and Competing Cancer Outcomes in Families With Li-Fraumeni Syndrome Using Clinically Ascertained Data.

PURPOSE: There exists a barrier between developing and disseminating risk prediction models in clinical settings. We hypothesize that this barrier may be lifted by demonstrating the utility of these models using incomplete data that are collected in real clinical sessions, as compared with the commonly used research cohorts that are meticulously collected. MATERIALS AND METHODS: Genetic counselors (GCs) collect family history when patients (ie, probands) come to MD Anderson Cancer Center for risk assessment of Li-Fraumeni syndrome, a genetic disorder characterized by deleterious germline mutations in the TP53 gene. Our clinical counseling-based (CCB) cohort consists of 3,297 individuals across 124 families (522 cases of single primary cancer and 125 cases of multiple primary cancers). We applied our software suite LFSPRO to make risk predictions and assessed performance in discrimination using AUC and in calibration using observed/expected (O/E) ratio. RESULTS: For prediction of deleterious TP53 mutations, we achieved an AUC of 0.78 (95% CI, 0.71 to 0.85) and an O/E ratio of 1.66 (95% CI, 1.53 to 1.80). Using the LFSPRO.MPC model to predict the onset of the second cancer, we obtained an AUC of 0.70 (95% CI, 0.58 to 0.82). Using the LFSPRO.CS model to predict the onset of different cancer types as the first primary, we achieved AUCs between 0.70 and 0.83 for sarcoma, breast cancer, or other cancers combined. CONCLUSION: We describe a study that fills in the critical gap in knowledge for the utility of risk prediction models. Using a CCB cohort, our previously validated models have demonstrated good performance and outperformed the standard clinical criteria. Our study suggests that better risk counseling may be achieved by GCs using these already-developed mathematical models.

Integrative analysis based on the cell cycle-related genes identifies TPX2 as a novel prognostic biomarker associated with tumor immunity in breast cancer.

BACKGROUND: This study aims to identify the essential cell cycle-related genes associated with prognosis in breast cancer (BRCA), and to verify the relationship between the central gene and immune infiltration, so as to provide detailed and comprehensive information for the treatment of BRCA. MATERIALS AND METHODS: Gene expression profiles (GSE10780, GSE21422, GSE61304) and the Cancer Genome Atlas (TCGA) BRCA data were used to identify differentially expressed genes (DEGs) and further functional enrichment analysis. STRING and Cytoscape were employed for the protein-protein interaction (PPI) network construction. TPX2 was viewed as the crucial prognostic gene by the Survival and Cox analysis. Furthermore, the connection between TPX2 expression and immune infiltrating cells and immune checkpoints in BRCA was also performed by the TIMER online database and R software. RESULTS: A total of 18 cell cycle-related DEGs were identified in this study. Subsequently, an intersection analysis based on TCGA-BRCA prognostic genes and the above DEGs identified three genes (TPX2, UBE2C, CCNE2) as crucial prognostic candidate biomarkers. Moreover, we also demonstrated that TPX2 is closely associated with immune infiltration in BRCA and a positive relation between TPX2 and PD-L1 expression was firstly detected. CONCLUSIONS: These results revealed that TPX2 is a potential prognostic biomarker and closely correlated with immune infiltration in BRCA, which could provide powerful and efficient strategies for breast cancer immunotherapy.

Transcriptomic Profiling of Plasma Extracellular Vesicles Enables Reliable Annotation of the Cancer-specific Transcriptome and Molecular Subtype.

Longitudinal monitoring of patients with advanced cancers is crucial to evaluate both disease burden and treatment response. Current liquid biopsy approaches mostly rely on the detection of DNA-based biomarkers. However, plasma RNA analysis can unleash tremendous opportunities for tumor state interrogation and molecular subtyping. Through the application of deep learning algorithms to the deconvolved transcriptomes of RNA within plasma extracellular vesicles (evRNA), we successfully predict consensus molecular subtypes in metastatic colorectal cancer patients. We further demonstrate the ability to monitor changes in transcriptomic subtype under treatment selection pressure and identify molecular pathways in evRNA associated with recurrence. Our approach also identified expressed gene fusions and neoepitopes from evRNA. These results demonstrate the feasibility of transcriptomic-based liquid biopsy platforms for precision oncology approaches, spanning from the longitudinal monitoring of tumor subtype changes to identification of expressed fusions and neoantigens as cancer-specific therapeutic targets, sans the need for tissue-based sampling.

A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations.

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to genes involved in neurological, thyroidal, bone metabolism, and hematopoietic pathways. Non-overlap between short sleep (12) and long sleep (10) interactions underscores the plausibility of distinct influences of both sleep duration extremes in cardiovascular health. With several of our loci reflecting specificity towards population background or sex, our discovery sheds light on the importance of embracing granularity when addressing heterogeneity entangled in gene-environment interactions, and in therapeutic design approaches for blood pressure management.

MyD88-mediated signaling is critical for the generation of seizure responses and cognitive impairment in a model of anti-N-methyl-D-aspartate receptor encephalitis.

OBJECTIVE: We previously demonstrated that interleukin-1 receptor-mediated immune activation contributes to seizure severity and memory loss in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. In the present study, we assessed the role of the myeloid differentiation primary response gene 88 (MyD88), an adaptor protein in Toll-like receptor signaling, in the key phenotypic characteristics of anti-NMDAR encephalitis. METHODS: Monoclonal anti-NMDAR antibodies or control antibodies were infused into the lateral ventricle of MyD88 knockout mice (MyD88-/- ) and control C56BL/6J mice (wild type [WT]) via osmotic minipumps for 2 weeks. Seizure responses were measured by electroencephalography. Upon completion of the infusion, the motor, anxiety, and memory functions of the mice were assessed. Astrocytic (glial fibrillary acidic protein [GFAP]) and microglial (ionized calcium-binding adaptor molecule 1 [Iba-1]) activation and transcriptional activation for the principal inflammatory mediators involved in seizures were determined using immunohistochemistry and quantitative real-time polymerase chain reaction, respectively. RESULTS: As shown before, 80% of WT mice infused with anti-NMDAR antibodies (n = 10) developed seizures (median = 11, interquartile range [IQR] = 3-25 in 2 weeks). In contrast, only three of 14 MyD88-/- mice (21.4%) had seizures (0, IQR = 0-.25, p = .01). The WT mice treated with antibodies also developed memory loss in the novel object recognition test, whereas such memory deficits were not apparent in MyD88-/- mice treated with anti-NMDAR antibodies (p = .03) or control antibodies (p = .04). Furthermore, in contrast to the WT mice exposed to anti-NMDAR antibodies, the MyD88-/- mice had a significantly lower induction of chemokine (C-C motif) ligand 2 (CCL2) in the hippocampus (p = .0001, Sidak tests). There were no significant changes in the expression of GFAP and Iba-1 in the MyD88-/- mice treated with anti-NMDAR or control antibodies. SIGNIFICANCE: These findings suggest that MyD88-mediated signaling contributes to the seizure and memory phenotype in anti-NMDAR encephalitis and that CCL2 activation may participate in the expression of these features. The removal of MyD88 inflammation may be protective and therapeutically relevant.

Thrombotic microenvironment responsive crosslinking cyclodextrin metal-organic framework nanocarriers for precise targeting and thrombolysis.

Global public health is seriously threatened by thrombotic disorders because of their high rates of mortality and disability. Most thrombolytic agents, especially protein-based pharmaceuticals, have a short half-life in circulation, reducing their effectiveness in thrombolysis. The creation of an intelligent drug delivery system that delivers medication precisely and releases it under regulated conditions at nearby thrombus sites is essential for effective thrombolysis. In this article, we present a unique medication delivery system (MCRUA) that selectively targets platelets and releases drugs by stimulation from the thrombus' microenvironment. The thrombolytic enzyme urokinase-type plasminogen-activator (uPA) and the anti-inflammatory medication Aspirin (acetylsalicylic acid, ASA) are both loaded onto pH-sensitive CaCO3/cyclodextrin crosslinking metal-organic frameworks (MC) that make up the MCRUA system. c(RGD) is functionalized on the surface of MC, which is functionalized by RGD to an esterification reaction. Additionally, the thrombus site's acidic microenvironment causes MCRUA to disintegrate to release uPA for thrombolysis and aiding in vessel recanalization. Moreover, cyclodextrin-encapsulated ASA enables the treatment of the inflammatory environment within the thrombus, enhancing the antiplatelet aggregation effects and promoting cooperative thrombolysis therapy. When used for thrombotic disorders, our drug delivery system (MCRUA) promotes thrombolysis, suppresses rethrombosis, and enhances biosafety with fewer hemorrhagic side effects.

ScRNA-seq reveals dark- and light-induced differentially expressed gene atlases of seedling leaves in Arachis hypogaea L.

Although the regulatory mechanisms of dark and light-induced plant morphogenesis have been broadly investigated, the biological process in peanuts has not been systematically explored on single-cell resolution. Herein, 10 cell clusters were characterized using scRNA-seq-identified marker genes, based on 13 409 and 11 296 single cells from 1-week-old peanut seedling leaves grown under dark and light conditions. 6104 genes and 50 transcription factors (TFs) displayed significant expression patterns in distinct cell clusters, which provided gene resources for profiling dark/light-induced candidate genes. Further pseudo-time trajectory and cell cycle evidence supported that dark repressed the cell division and perturbed normal cell cycle, especially the PORA abundances correlated with 11 TFs highly enriched in mesophyll to restrict the chlorophyllide synthesis. Additionally, light repressed the epidermis cell developmental trajectory extending by inhibiting the growth hormone pathway, and 21 TFs probably contributed to the different genes transcriptional dynamic. Eventually, peanut AHL17 was identified from the profile of differentially expressed TFs, which encoded protein located in the nucleus promoted leaf epidermal cell enlargement when ectopically overexpressed in Arabidopsis through the regulatory phytohormone pathway. Overall, our study presents the different gene atlases in peanut etiolated and green seedlings, providing novel biological insights to elucidate light-induced leaf cell development at the single-cell level.

Simulation of emission reduction path under the path of differentiated energy transformation in China's industrial cities: a case study of Shanghai.

The formulation of long-term step-by-step emission reduction plan is an important step for effective scientific emission reduction. This paper takes Shanghai as the research object, constructs PSO-LSTM model on the basis of STIRPAT model, and further constructs three dynamic policy scenarios combined with China's actual situation and makes short-, medium-, and long-term multivariate predictions for them. The study finds that only the improvement of energy consumption structure has a promotion effect on carbon emission reduction, and urbanization, industrial structure, technology level, population, and economic level all have an increasing effect, and secondly, the carbon emission reduction path of Shanghai basically achieves the core objective of steady decrease under the three scenarios. Secondly, under the three scenarios, Shanghai's carbon emission reduction path basically achieves the core objective of steady decline, but the decline in the GU scenario is more significant. It is recommended that Shanghai further adjusts its industrial structure, optimizes its energy consumption structure, promotes technological innovation and progress, and promotes the development of the circular economy model.

LFSPROShiny: An Interactive R/Shiny App for Prediction and Visualization of Cancer Risks in Families With Deleterious Germline TP53 Mutations.

PURPOSE: LFSPRO is an R library that implements risk prediction models for Li-Fraumeni syndrome (LFS), a genetic disorder characterized by deleterious germline mutations in the TP53 gene. To facilitate the use of these models in clinics, we developed LFSPROShiny, an interactive R/Shiny interface of LFSPRO that allows genetic counselors (GCs) to perform risk predictions without any programming components and further visualize the risk profiles of their patients to aid the decision-making process. METHODS: LFSPROShiny implements two models that have been validated on multiple LFS patient cohorts: a competing risk model that predicts cancer-specific risks for the first primary and a recurrent-event model that predicts the risk of a second primary tumor. Starting with a visualization template, we keep regular contact with GCs, who ran LFSPROShiny in their counseling sessions, to collect feedback and discuss potential improvement. On receiving the family history as input, LFSPROShiny renders the family into a pedigree and displays the risk estimates of the family members in a tabular format. The software offers interactive overlaid side-by-side bar charts for visualization of the patients' cancer risks relative to the general population. RESULTS: We walk through a detailed example to illustrate how GCs can run LFSPROShiny in clinics from data preparation to downstream analyses and interpretation of results with an emphasis on the utilities that LFSPROShiny provides to aid decision making. CONCLUSION: Since December 2021, we have applied LFSPROShiny to over 100 families from counseling sessions at the MD Anderson Cancer Center. Our study suggests that software tools with easy-to-use interfaces are crucial for the dissemination of risk prediction models in clinical settings, hence serving as a guideline for future development of similar models.

Antioxidant Hydrogels: Antioxidant Mechanisms, Design Strategies, and Applications in the Treatment of Oxidative Stress-Related Diseases.

Oxidative stress is a biochemical process that disrupts the redox balance due to an excess of oxidized substances within the cell. Oxidative stress is closely associated with a multitude of diseases and health issues, including cancer, diabetes, cardiovascular diseases, neurodegenerative disorders, inflammatory conditions, and aging. Therefore, the developing of antioxidant treatment strategies has emerged as a pivotal area of medical research. Hydrogels have garnered considerable attention due to their exceptional biocompatibility, adjustable physicochemical properties, and capabilities for drug delivery. Numerous antioxidant hydrogels have been developed and proven effective in alleviating oxidative stress. In the pursuit of more effective treatments for oxidative stress-related diseases, there is an urgent need for advanced strategies for the fabrication of multifunctional antioxidant hydrogels. Consequently, the authors' focus will be on hydrogels that possess exceptional reactive oxygen species and reactive nitrogen species scavenging capabilities, and their role in oxidative stress therapy will be evaluated. Herein, the antioxidant mechanisms and the design strategies of antioxidant hydrogels and their applications in oxidative stress-related diseases are discussed systematically in order to provide critical insights for further advancements in the field.

Development and validation of a novel lysosome-related LncRNA signature for predicting prognosis and the immune landscape features in colon cancer.

Lysosomes are essential components for managing tumor microenvironment and regulating tumor growth. Moreover, recent studies have also demonstrated that long non-coding RNAs could be used as a clinical biomarker for diagnosis and treatment of colorectal cancer. However, the influence of lysosome-related lncRNA (LRLs) on the progression of colon cancer is still unclear. This study aimed to identify a prognostic LRL signature in colon cancer and elucidated potential biological function. Herein, 10 differential expressed lysosome-related genes were obtained by the TCGA database and ultimately 4 prognostic LRLs for conducting a risk model were identified by the co-expression, univariate cox, least absolute shrinkage and selection operator analyses. Kaplan-Meier analysis, principal-component analysis, functional enrichment annotation, and nomogram were used to verify the risk model. Besides, the association between the prognostic model and immune infiltration, chemotherapeutic drugs sensitivity were also discussed in this study. This risk model based on the LRLs may be promising for potential clinical prognosis and immunotherapeutic responses related indicator in colon cancer patients.

Reactivation of the G1 enhancer landscape underlies core circuitry addiction to SWI/SNF.

Several cancer core regulatory circuitries (CRCs) depend on the sustained generation of DNA accessibility by SWI/SNF chromatin remodelers. However, the window when SWI/SNF is acutely essential in these settings has not been identified. Here we used neuroblastoma (NB) cells to model and dissect the relationship between cell-cycle progression and SWI/SNF ATPase activity. We find that SWI/SNF inactivation impairs coordinated occupancy of non-pioneer CRC members at enhancers within 1 hour, rapidly breaking their autoregulation. By precisely timing inhibitor treatment following synchronization, we show that SWI/SNF is dispensable for survival in S and G2/M, but becomes acutely essential only during G1 phase. We furthermore developed a new approach to analyze the oscillating patterns of genome-wide DNA accessibility across the cell cycle, which revealed that SWI/SNF-dependent CRC binding sites are enriched at enhancers with peak accessibility during G1 phase, where they activate genes involved in cell-cycle progression. SWI/SNF inhibition strongly impairs G1-S transition and potentiates the ability of retinoids used clinically to induce cell-cycle exit. Similar cell-cycle effects in diverse SWI/SNF-addicted settings highlight G1-S transition as a common cause of SWI/SNF dependency. Our results illustrate that deeper knowledge of the temporal patterns of enhancer-related dependencies may aid the rational targeting of addicted cancers.

Cancer cells driven by runaway transcription factor networks frequently depend on the cellular machinery that promotes DNA accessibility. For this reason, recently developed small molecules that impair SWI/SNF (or BAF) chromatin remodeling activity have been under active evaluation as anti-cancer agents. However, exactly when SWI/SNF activity is essential in dependent cancers has remained unknown. By combining live-cell imaging and genome-wide profiling in neuroblastoma cells, Cermakova et al. discover that SWI/SNF activity is needed for survival only during G1 phase of the cell cycle. The authors reveal that in several cancer settings, dependency on SWI/SNF arises from the need to reactivate factors involved in G1-S transition. Because of this role, authors find that SWI/SNF inhibition potentiates cell-cycle exit by retinoic acid.

Diagnostic Value of Quantitative Ultrasound for Osteoporosis in Elderly Women: A Meta-Analysis.

Objective: To assess the reliability of quantitative ultrasound (QUS) in diagnosing and screening osteoporosis in elder women. Methods: We conducted a systematic search of the online databases, including PubMed, Embase, Web of Science, and China National Knowledge, and screened the studies according to the inclusion criteria. We directly extract or calculate the value of true positive (TP), false positive (FP), false negative (FN), and true negative (TN) from eligible studies. We sought to evaluate the diagnostic parameters of QUS, containing the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC). Results: Twelve studies were included in this study with a total of 2260 women. QUS showed a pooled diagnostic odds ratio of 5.07 (95% CI 3.28-7.84), sensitivity of 0.69 (95% CI 0.65-0.72), specificity of 0.67 (95% CI 0.64-0.69), and an AUC of 0.7523 (Q*=0.6953). There was no obvious heterogeneity and threshold effect according to the Spearman correlation coefficient (P = 0.059). No significant publication bias was found through the Deek's funnel. Conclusion: Our study suggested that the diagnostic value of QUS for osteoporosis in elder women was acceptable, but the accuracy still needed to be improved, QUS can be recommended as a pre-screening tool for osteoporosis to determine whether DXA measurement was needed.

A Single-Nucleus Resolution Atlas of Transcriptome and Chromatin Accessibility for Peanut (Arachis Hypogaea L.) Leaves.

The peanut is an important worldwide cash-crop for edible oil and protein. However, the kinetic mechanisms that determine gene expression and chromatin accessibility during leaf development in peanut represented allotetraploid leguminous crops are poorly understood at single-cell resolution. Here, a single-nucleus atlas of peanut leaves is developed by simultaneously profiling the transcriptome and chromatin accessibility in the same individual-cell using fluorescence-activated sorted single-nuclei. In total, 5930 cells with 50 890 expressed genes are classified into 18 cell-clusters, and 5315 chromatin fragments are enriched with 26 083 target genes in the chromatin accessible landscape. The developmental trajectory analysis reveals the involvement of the ethylene-AP2 module in leaf cell differentiation, and cell-cycle analysis demonstrated that genome replication featured in distinct cell-types with circadian rhythms transcription factors (TFs). Furthermore, dual-omics illustrates that the fatty acid pathway modulates epidermal-guard cells differentiation and providescritical TFs interaction networks for understanding mesophyll development, and the cytokinin module (LHY/LOG) that regulates vascular growth. Additionally, an AT-hook protein AhAHL11 is identified that promotes leaf area expansion by modulating the auxin content increase. In summary, the simultaneous profiling of transcription and chromatin accessibility landscapes using snRNA/ATAC-seq provides novel biological insights into the dynamic processes of peanut leaf cell development at the cellular level.

CRISPR-Cas9-based functional interrogation of unconventional translatome reveals human cancer dependency on cryptic non-canonical open reading frames.

Emerging evidence suggests that cryptic translation beyond the annotated translatome produces proteins with developmental or physiological functions. However, functions of cryptic non-canonical open reading frames (ORFs) in cancer remain largely unknown. To fill this gap and systematically identify colorectal cancer (CRC) dependency on non-canonical ORFs, we apply an integrative multiomic strategy, combining ribosome profiling and a CRISPR-Cas9 knockout screen with large-scale analysis of molecular and clinical data. Many such ORFs are upregulated in CRC compared to normal tissues and are associated with clinically relevant molecular subtypes. We confirm the in vivo tumor-promoting function of the microprotein SMIMP, encoded by a primate-specific, long noncoding RNA, the expression of which is associated with poor prognosis in CRC, is low in normal tissues and is specifically elevated in CRC and several other cancer types. Mechanistically, SMIMP interacts with the ATPase-forming domains of SMC1A, the core subunit of the cohesin complex, and facilitates SMC1A binding to cis-regulatory elements to promote epigenetic repression of the tumor-suppressive cell cycle regulators encoded by CDKN1A and CDKN2B. Thus, our study reveals a cryptic microprotein as an important component of cohesin-mediated gene regulation and suggests that the 'dark' proteome, encoded by cryptic non-canonical ORFs, may contain potential therapeutic or diagnostic targets.