Amorphous CoFePOx hollow nanocubes decorated with g-C3N4 quantum dots to achieve efficient electrocatalytic performance in the oxygen evolution reaction.

Simultaneously enriching active sites and enhancing intrinsic activity in a simple way is of great importance for the design of highly active electrocatalysts for the oxygen evolution reaction (OER), but it still faces challenges. Herein, g-C3N4 quantum dot decorated amorphous hollow CoFe bimetallic phosphate nanocubes (a-CoFePOx@CNQD) are prepared as an efficient OER electrocatalyst by a simple in situ etching-phosphating process. Research shows that their unique hollow architecture and amorphous structure can help provide generous exposed active sites for OER, and the incorporation of g-C3N4 quantum dots can effectively adjust the electronic structure to improve the intrinsic activity. Therefore, a-CoFePOx@CNQD exhibits excellent OER performance with a low overpotential (239 mV) at 10 mA cm-2 and a small Tafel slope (58.4 mV dec-1), surpassing the commercial RuO2. Furthermore, a-CoFePOx@CNQD as an electrode catalyst for a water electrolyzer and zinc-air battery also shows higher performance and stability than RuO2 + Pt/C catalysts. This study provides a feasible strategy for preparing efficient and stable amorphous hollow heterostructure OER electrocatalysts.

The Effect of Job Skill Demands Under Artificial Intelligence Embeddedness on Employees' Job Performance: A Moderated Double-Edged Sword Model.

With the widespread application of AI technology, the skills and abilities required by employees in their work are undergoing fundamental changes, redefining the roles of employees. This research aims to explore the effect of job skill demands under AI embeddedness on well-being in organizations and job performance. Based on conservation of resources theory, this research randomly selected 479 employees from 8 companies in China using a time-lag method as samples, and conducted statistical analysis with ordinary least squares (OLS). This research found that, job skill demands under AI embeddedness will both increase employees' competency needs, promoting their well-being in organizations and job performance and decrease employees' job embeddedness, inhibiting their well-being in organizations and job performance. Meanwhile, technological anxiety moderated the impact of job skill demands under AI embeddedness on job embeddedness.

SUPERMAN Targets PHRAGMOPLAST ORIENTING KINESIN to Negatively Regulate Leaf Cell Division in Poplar.

Plant organs achieve their specific size and shape through the coordination of cell division and cell expansion, processes that are profoundly influenced by environmental cues. Cytokinesis during cell division depends on the position of the cytokinetic wall, but how this process responses to environment fluctuations remains underexplored. Here, we investigated a regulatory module involving C2H2-type zinc finger protein (C2H2-ZFP) in leaf morphology during drought stress. A total of 123 C2H2-ZFP members were identified through a comparative genome survey in Populus alba × P. glandulosa '84K'. Among them, PagSUPa, an orthologous gene of Arabidopsis SUPERMAN, was selected due to its responsiveness to drought stress and was further confirmed to play a role in leaf development. Phenotypic characterization and cellular analysis revealed that PagSUPa fine-tunes the duration of cell proliferation in the adaxial epidermis, thereby influencing leaf morphology by modulating leaf adaxial-abaxial polarity. Additionally, we found that PagSUPa directly suppresses the expression of PHRAGMOPLAST ORIENTING KINESIN1 (PagPOK1) and PagPOK2, genes encoding proteins involved in phragmoplast orientation and position, which results in impaired cytokinesis and cell wall organization. This study provides novel insights into the regulatory network governed by the SUP gene during leaf development, specifically in relation to cell division.

FNIP1 suppresses colorectal cancer progression through inhibiting STAT3 phosphorylation and nuclear translocation.

Folliculin interacting protein 1 (FNIP1) primarily participates in regulating cellular energy metabolism and is associated with Birt-Hogg-Dubé (BHD) syndrome. Although FNIP1 has been demonstrated to function as both a tumor suppressor and promoter, its role in colorectal cancer (CRC) remains unclear. Our study demonstrated a significant downregulation of FNIP1 in CRC, correlating with shorter overall and disease-specific survival. FNIP1 may potentially serve as an independent prognostic factor in CRC. Moreover, FNIP1 inhibited CRC progression in vitro and in vivo. Mechanistically, FNIP1 bound to phosphorylated signal transducer and activator of transcription-3 (p-STAT3) and downregulated its expression. FNIP1 deletion increased STAT3 phosphorylation and nuclear localization, thereby promoting CRC progression. The use of p-STAT3-specific chemical inhibitors successfully mitigated excessive tumorigenesis resulting from FNIP1 absence. Thus, our results suggest that FNIP1 hinders CRC progression by suppressing STAT3 phosphorylation and nuclear translocation. FNIP1 may be a candidate prognostic indicator and a therapeutic target for intervention in CRC.

Predicting Long-Term Outcome of Prolonged Disorder of Consciousness in Children Through Machine Learning Based on Conventional Structural Magnetic Resonance Imaging.

BACKGROUND: The prognosis of prolonged disorders of consciousness (pDoC) in children has consistently posed a formidable challenge in clinical decision-making. OBJECTIVE: This study aimed to develop a machine learning (ML) model based on conventional structural magnetic resonance imaging (csMRI) to predict outcomes in children with pDoC. METHODS: A total of 196 children with pDoC were included in this study. Based on the consciousness states 1 year after brain injury, the children were categorized into either the favorable prognosis group or the poor prognosis group. They were then randomly assigned to the training set (n = 138) or the test set (n = 58). Semi-quantitative visual assessments of brain csMRI were conducted and Least Absolute Shrinkage and Selection Operator regression was used to identify significant features predicting outcomes. Based on the selected features, support vector machine (SVM), random forests (RF), and logistic regression (LR) were used to develop csMRI, clinical, and csMRI-clinical-merge models, respectively. Finally, the performances of all models were evaluated. RESULTS: Seven csMRI features and 4 clinical features were identified as important predictors of consciousness recovery. All models achieved satisfactory prognostic performances (all areas under the curve [AUCs] >0.70). Notably, the csMRI model developed using the SVM exhibited the best performance, with an AUC, accuracy, sensitivity, and specificity of 0.851, 0.845, 0.844, and 0.846, respectively. CONCLUSIONS: A csMRI-based prediction model for the prognosis of children with pDoC was developed, showing potential to predict recovery of consciousness 1 year after brain injury and is worth popularizing in clinical practice.

Strengthening mechanism of sub-nano Ni3P and Cu3P phases particles on the Pb-Sn bronze alloy.

The influence of the sub-nano Ni3P and Cu3P phases on the microstructure, mechanical properties, and strengthening mechanism of Cu-20Pb-5Sn-xP (x = 0,0.05,0.1,0.3,0.5) alloy were discussed under the addition of P to obtain a new Pb-Sn bronze alloy applying for bimetallic cylinder block. The results showed that the tensile strength and hardness of the Pb-Sn bronze alloy increase with the P contents, while the elongation increased first and then decreased. The main strengthen mechanism was that sub-nano Ni3P and Cu3P phases dispersed in the matrix, hindering the movement of dislocations during deformation. Additionally, the grain refinement also contributed to the improvement of mechanical properties. The Ni3P phase is easier to form than the Cu3P phase. And it is easier to combine with the matrix and more stable. The Ni3P and Cu3P phases were studied by using different characterization techniques, such as OM, SEM, EDS, XRD, TEM and First-principles, Phase diagram calculation method. When P is added to the alloy, the Ni3P phase first appears in the alloy, and when the P content increases to more than 0.3 wt%, the Cu3P phase begins to appear. This is because the Ni3P phase is easier to form than the Cu3P phase and is more stable. Only after part of P reacts with Ni dissolved in copper to form Ni3P, the remaining P and Cu can form Cu3P.

piR-27222 mediates PM2.5-induced lung cancer by resisting cell PANoptosis through the WTAP/m6A axis.

PM2.5 pollution has been associated with the incidence of lung cancer, but the underlying mechanism is still unclear. PIWI-interacting RNAs (piRNAs), initially identified in germline cells, have emerged as a novel class of small non-coding RNAs (26 - 32 nucleotides) with diverse functions in various diseases, including cancer. However, the role and mechanism of piRNAs in the development of PM2.5-induced lung cancer remain to be clarified. In the presented study, we used a PM2.5-induced malignant transformation cell model to analyze the change of piRNA profiles. Among the disturbed piRNAs, piR-27222 was identified as an oncogene that inhibited cell death in a m6A-dependent manner. Mechanistically, we found that piR-27222 could deubiquitinate and stabilize eIF4B by directly binding to eIF4B and reducing its interaction with PARK2. The enhanced expression of eIF4B, in turn, promoted the expression of WTAP, leading to increased m6A modification in the Casp8 transcript. Consequently, the stability of Casp8 transcripts was reduced, rendering lung cancer cells resistant to PANoptosis. Collectively, our findings reveal that PM2.5 exposure up-regulated piR-27222 expression, which could affect EIF4B/WTAP/m6A axis, thereby inhibiting PANoptosis of cells and promoting lung cancer. Our study provides new insights into understanding the epigenetic mechanisms underlining PM2.5-induced lung cancer.

Exosomes originating from neural stem cells undergoing necroptosis participate in cellular communication by inducing TSC2 upregulation of recipient cells following spinal cord injury.

ABSTRACT: We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord injury. While exosomes are recognized as playing a pivotal role in neural stem cells exocrine function, their precise function in spinal cord injury remains unclear. To investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury, we conducted single-cell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord injury. Subsequently, we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted exosomes. The results showed that necroptosis did not significantly impact the fundamental characteristics or number of exosomes. Transcriptome sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs, 104 long non-coding RNAs, 720 circular RNAs, and 14 microRNAs compared with the control group. Construction of a competing endogenous RNA network identified the following hub genes: tuberous sclerosis 2 (Tsc2), solute carrier family 16 member 3 (Slc16a3), and forkhead box protein P1 (Foxpl). Notably, a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord injury. TSC2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury zone. Furthermore, in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other cells. Further assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling pathways. In addition, Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling pathways. Collectively, these findings confirm that exosomes derived from neural stem cells undergoing necroptosis play an important role in cellular communication after spinal cord injury and induce TSC2 upregulation in recipient cells.

The validity and reliability of the Chinese version of the biological rhythms interview of assessment in neuropsychiatry in the community: a large Chinese college student population.

Objective: To test the psychometric properties of the Chinese version of the biological rhythms interview of assessment in neuropsychiatry (C-BRIAN) in a group of young adults with and without depressive symptoms. Methods: Three hundred and seventy-eight university students were recruited as participants. Based on the scores from Center for Epidemiological Survey Depression Scale (CES-D), students were divided into the depressed group and healthy group. Explorative factor analysis was applied to assess the construct validity of the C-BRIAN. The Pittsburgh Sleep Quality Index (PSQI) and CES-D were compared with the C-BRIAN to test the convergent validity. The internal consistency of the C-BRIAN was also examined. Results: Three factors were extracted (activities, eating patterns, and sleep factors) explaining 63.9% of the total variance. The internal consistencies were very good with a coefficient of 0.94 (overall) and 0.89-0.91 for three factors. The domains of activities, eating patterns, and sleep were moderately correlated with PSQI (r=0.579) and CES-D (r=0.559) (ps<0.01). Conclusion: Our findings suggest that C-BRIAN has good validity and reliability which can be used to assess the biological rhythm in the young adult population with depressive symptoms. C-BRIAN would be a reliable tool to detect depressive symptoms for timely prevention and intervention in the community.

Clinical characteristics and rehabilitation potential in children with cerebral palsy based on MRI classification system.

Background: The correlation of clinical characteristics of cerebral palsy (CP) and the magnetic resonance imaging classification system (MRICS) for (CP) is inconsistent. Specifically, the variance in rehabilitation potential across MRICS remains underexplored. Aims: To investigate the clinical characteristics and potential for rehabilitation in children with CP based on MRICS. Materials and methods: Children with CP admitted to the Department of Rehabilitation, Children's Hospital of Chongqing Medical University between 2017 and 2021 were included in the study. Qualified cases underwent a follow-up period of at least one year. The clinical characteristics of CP among different MRICS were analyzed, then the rehabilitation potential was explored by a retrospective cohort study. Results: Among the 384 initially enrolled children, the male-to-female ratio was 2.3:1, and the median age of diagnosis was 6.5 months (interquartile range: 4-12). The most prevalent MRICS categorization was predominant white matter injury (40.6%), followed by miscellaneous (29.2%) and predominant gray matter injury (15.6%). For the predominant white matter injury and miscellaneous categories, spastic diplegia emerged as the leading subtype of CP, with incidences of 59.6% and 36.6%, respectively, while mixed CP (36.7%) was the most common type in children with predominant gray matter. Notably, 76.4% of children with predominant white matter injury were classified as levels I-III on the gross motor function classification system (GMFCS), indicating significantly less severity than other groups (χ2 = 12.438, p = 0.013). No significant difference across MRICS categories was observed for the manual ability classification system (MACS) (H = 8.176, p = 0.085). Rehabilitation potential regarding fine motor function and adaptability based on Gesell assessment was dependent on MRICS over the follow-up period. Children with normal MRI scans exhibited superior rehabilitation outcomes. Commencing rehabilitation at an earlier stage produced consistent and beneficial results in terms of fine motor function and adaptability across all MRICS categories. Moreover, participants below 2 years of age demonstrated enhanced rehabilitation potential regarding fine motor outcomes and adaptability within the MRICS framework. Conclusion: MRICS displayed a significant association with clinical characteristics and rehabilitation efficacy in children with CP.

PagPXYs improve drought tolerance by regulating reactive oxygen species homeostasis in the cambium of Populus alba × P. glandulosa.

PXY (Phloem intercalated with xylem) is a receptor kinase required for directional cell division during the development of plant vascular tissue. Drought stress usually affects plant stem cell division and differentiation thereby limiting plant growth. However, the role of PXY in cambial activities of woody plants under drought stress is unclear. In this study, we analyzed the biological functions of two PXY genes (PagPXYa and PagPXYb) in poplar growth and development and in response to drought stress in a hybrid poplar (Populus alba × P. glandulosa, '84K'). Expression analysis indicated that PagPXYs, similar to their orthologs PtrPXYs in Populus trichocarpa, are mainly expressed in the stem vascular system, and related to drought. Interestingly, overexpression of PagPXYa and PagPXYb in poplar did not have a significant impact on the growth status of transgenic plants under normal condition. However, when treated with 8 % PEG6000 or 100 mM H2O2, PagPXYa and PagPXYb overexpressing lines consistently exhibited more cambium cell layers, fewer xylem cell layers, and enhanced drought tolerance compared to the non-transgenic control '84K'. In addition, PagPXYs can alleviate the damage caused by H2O2 to the cambium under drought stress, thereby maintaining the cambial division activity of poplar under drought stress, indicating that PagPXYs play an important role in plant resistance to drought stress. This study provides a new insight for further research on the balance of growth and drought tolerance in forest trees.

Evaluation of novel promoters for vascular tissue-specific gene expression in Populus.

Due to the extended generation cycle of trees, the breeding process for forest trees tends to be time-consuming. Genetic engineering has emerged as a viable approach to expedite the genetic breeding of forest trees. However, current genetic engineering techniques employed in forest trees often utilize continuous expression promoters such as CaMV 35S, which may result in unintended consequences by introducing genes into non-target tissues. Therefore, it is imperative to develop specific promoters for forest trees to facilitate targeted and precise design and breeding. In this study, we utilized single-cell RNA-Seq data and co-expression network analysis during wood formation to identify three vascular tissue-specific genes in poplar, PP2-A10, PXY, and VNS07, which are expressed in the phloem, cambium/expanding xylem, and mature xylem, respectively. Subsequently, we cloned the promoters of these three genes from '84K' poplar and constructed them into a vector containing the eyGFPuv visual selection marker, along with the 35S mini enhancer to drive GUS gene expression. Transgenic poplars expressing the ProPagPP2-A10::GUS, ProPagPXY::GUS, and ProPagVNS07::GUS constructs were obtained. To further elucidate the tissue specificity of these promoters, we employed qPCR, histochemical staining, and GUS enzyme activity. Our findings not only establish a solid foundation for the future utilization of these promoters to precisely express of specific functional genes in stems but also provide a novel perspective for the modular breeding of forest trees.

Comparative analysis of PLATZ transcription factors in six poplar species and analysis of the role of PtrPLATZ14 in leaf development.

Plant AT-rich sequence and zinc-binding (PLATZ) proteins are a class of plant-specific transcription factor that play a crucial role in plant growth, development, and stress response. However, the evolutionary relationship of the PLATZ gene family across the Populus genus and the biological functions of the PLATZ protein require further investigation. In this study, we identified 133 PLATZ genes from six Populus species belonging to four Populus sections. Synteny analysis of the PLATZ gene family indicated that whole genome duplication events contributed to the expansion of the PLATZ family. Among the nine paralogous pairs, the protein structure of PtrPLATZ14/18 pair exhibited significant differences with others. Through gene expression patterns and co-expression networks, we discovered divergent expression patterns and sub-networks, and found that the members of pair PtrPLATZ14/18 might play different roles in the regulation of macromolecule biosynthesis and modification. Furthermore, we found that PtrPLATZ14 regulates poplar leaf development by affecting cell size control genes PtrGRF/GIF and PtrTCP. In conclusion, our study provides a theoretical foundation for exploring the evolution relationships and functions of the PLATZ gene family within Populus species and provides insights into the function and potential mechanism of PtrPLATZ14 in leaf morphology that were diverse across the Populus genus.

Extracellular vesicles released by transforming growth factor-beta 1-preconditional mesenchymal stem cells promote recovery in mice with spinal cord injury.

Spinal cord injury (SCI) causes neuroinflammation, neuronal death, and severe axonal connections. Alleviating neuroinflammation, protecting residual cells and promoting neuronal regeneration via endogenous neural stem cells (eNSCs) represent potential strategies for SCI treatment. Extracellular vesicles (EVs) released by mesenchymal stem cells have emerged as pathological mediators and alternatives to cell-based therapies following SCI. In the present study, EVs isolated from untreated (control, C-EVs) and TGF-ß1-treated (T-EVs) mesenchymal stem cells were injected into SCI mice to compare the therapeutic effects and explore the underlying mechanisms. Our study demonstrated for the first time that the application of T-EVs markedly enhanced the proliferation and antiapoptotic ability of NSCs in vitro. The infusion of T-EVs into SCI mice increased the shift from the M1 to M2 polarization of reactive microglia, alleviated neuroinflammation, and enhanced the neuroprotection of residual cells during the acute phase. Moreover, T-EVs increased the number of eNSCs around the epicenter. Consequently, T-EVs further promoted neurite outgrowth, increased axonal regrowth and remyelination, and facilitated locomotor recovery in the chronic stage. Furthermore, the use of T-EVs in Rictor-/- SCI mice (conditional knockout of Rictor in NSCs) showed that T-EVs failed to increase the activation of eNSCs and improve neurogenesis sufficiently, which suggested that T-EVs might induce the activation of eNSCs by targeting the mTORC2/Rictor pathway. Taken together, our findings indicate the prominent role of T-EVs in the treatment of SCI, and the therapeutic efficacy of T-EVs for SCI treatment might be optimized by enhancing the activation of eNSCs via the mTORC2/Rictor signaling pathway.

PPML-Omics: A privacy-preserving federated machine learning method protects patients' privacy in omic data.

Modern machine learning models toward various tasks with omic data analysis give rise to threats of privacy leakage of patients involved in those datasets. Here, we proposed a secure and privacy-preserving machine learning method (PPML-Omics) by designing a decentralized differential private federated learning algorithm. We applied PPML-Omics to analyze data from three sequencing technologies and addressed the privacy concern in three major tasks of omic data under three representative deep learning models. We examined privacy breaches in depth through privacy attack experiments and demonstrated that PPML-Omics could protect patients' privacy. In each of these applications, PPML-Omics was able to outperform methods of comparison under the same level of privacy guarantee, demonstrating the versatility of the method in simultaneously balancing the privacy-preserving capability and utility in omic data analysis. Furthermore, we gave the theoretical proof of the privacy-preserving capability of PPML-Omics, suggesting the first mathematically guaranteed method with robust and generalizable empirical performance in protecting patients' privacy in omic data.

An innovative approach to assess spinal canal expansion following French-door cervical laminoplasty by intraoperative ultrasonography.

OBJECTIVE: To investigate the feasibility and effectiveness of applying intraoperative ultrasound (IOUS) to evaluate spinal canal expansion in patients undergoing French-door cervical laminoplasty (FDCL). MATERIALS AND METHODS: Twenty-five patients who underwent FDCL for multilevel degenerative cervical myelopathy were prospectively recruited. Formulae describing the relationship between laminoplasty opening angle (LOA) and laminoplasty opening size, the increase in sagittal canal diameter and the spinal canal area were deduced with trigonometric functions. The LOA was measured with IOUS imaging during surgery, and other spinal canal parameters were assessed. Actual spinal canal enlargement was verified on postoperative CT images. Linear correlation analysis and Bland‒Altman analysis were used to evaluate correlation and agreement between the intraoperative and postoperative measurements. RESULTS: The LOA at C5 measured with IOUS was 27.54 ± 3.12°, and it was 27.23 ± 3.02° on postoperative CT imaging. Linear correlation analysis revealed a significant correlation between IOUS and postoperative CT measurements (r = 0.88; p < 0.01). Bland-Altman plots showed good agreement between these two methods, with a mean difference of 0.30°. For other spinal canal expansion parameter measurements, correlation analysis showed a moderate to a high degree of correlation (p < 0.01), and Bland-Altman analysis indicated good agreement. CONCLUSION: In conclusion, during the French-door cervical laminoplasty procedure, application of IOUS can accurately evaluate spinal canal expansion. This innovative method may be helpful in improving surgical accuracy by enabling the operator to measure and determine canal enlargement during surgery, leading to ideal clinical outcomes and fewer postoperative complications. CLINICAL RELEVANCE STATEMENT: The use of intraoperative ultrasonography to assess spinal canal expansion following French-door cervical laminoplasty may improve outcomes for patients undergoing this procedure by providing more accurate measurements of spinal canal expansion. KEY POINTS: • Spinal canal expansion after French-door cervical laminoplasty substantially influences operative prognosis; insufficient or excessive lamina opening may result in unexpected outcomes. • Prediction of spinal canal expansion during surgery was previously impracticable, but based on this study, intraoperative ultrasonography offers an innovative approach and strongly agrees with postoperative CT measurement. • Since this is the first research to offer real-time canal expansion guidance for cervical laminoplasty, it may improve the accuracy of the operation and produce ideal clinical outcomes with fewer postoperative complications.

Research on Three-Dimensional Shape Curve Reconstruction Technology for a Scraper Conveyor on an Intelligent Working Face.

"Three straight and two flat" is the inevitable demand when realizing the intelligent mining of a fully mechanized mining face. To address the crucial technical issue of lacking accurate perception of the shape of the scraper conveyor during intelligent coal mining, a three-dimensional curvature sensor involving fiber Bragg grating (FBG) is used as a perceptive tool to conduct curve reconstruction research based on different local motion frames and to reconstruct the shape of the scraper conveyor. Firstly, the formation process of the 'S'-shaped bending section of the scraper conveyor during the pushing process is determined. Based on the FBG sensing principle, a mathematical model between the variation in the central wavelength and the strain and curvature is established, and the cubic B-spline interpolation method is employed to continuously process the obtained discrete curvature. Secondly, based on differential geometry, a spatial curve reconstruction algorithm based on the Frenet moving frame is derived, and the shape curve prediction interpolation model is built based on a gated recurrent unit (GRU) model, which reduces the impact of the decrease in curve reconstruction accuracy caused by damage to some grating measuring points. Finally, an experimental platform was designed and built, and sensors with curvature radii of 6 m, 7 m, and 8 m were tested. The experimental results showed that the reconstructed curve was essentially consistent with the actual shape, and the absolute error at the end was about 2 mm. The feasibility of this reconstruction algorithm in engineering has been proven, and this is of great significance in achieving shape curve perception and straightness control for scraper conveyors.

Massive underrepresentation of Arabs in genomic studies of common disease.

Arabs represent 5% of the world population and have a high prevalence of common disease, yet remain greatly underrepresented in genome-wide association studies, where only 1 in 600 individuals are Arab. We highlight the persistent and unaddressed underrepresentation of Arabs in genomic databases and discuss its impact on public health genomics and missed opportunities for biological discovery.

Lysine ß-hydroxybutyrylation promotes lipid accumulation in alcoholic liver disease.

Continuous (chronic or sub-chronic) alcohol consumption induces a metabolic byproduct known as ketone bodies, and the accumulation of ketones leads to a life-threatening syndrome called alcoholic ketoacidosis. However, the mechanism underlining the physiological effects of ketone accumulation in alcoholic liver disease (ALD) is still in its infancy. Here, we discovered that mitochondrial acetyl-CoA accumulation was diverted into the ketogenesis pathway in ethanol-fed mice and ethanol-exposed hepatocytes. Unexpectedly, global protein lysine ß-hydroxybutyrylation (Kbhb) was induced in response to increased ketogenesis-derived ß-hydroxybutyrate (BHB) levels both in hepatocytes and in livers of mice. Focusing on the solute carrier family (SLCs), we found that SLC25A5 presented obvious Kbhb at lysine residues 147 and 166. Kbhb modifications at these two lysine residues stabilized SLC25A5 expression by blocking ubiquitin-proteasome pathway. Subsequent mutation analysis revealed that Kbhb of SLC25A5 at K147 and K166 had site-specific regulatory roles by increasing peroxisome proliferator activated receptor gamma (PPARγ) expression, which further promoting lipogenesis. Additionally, 3-hydroxy-3-methylglutaryl-coenzyme A synthase 2 (HMGCS2), a rate-limiting enzyme for BHB production, was profoundly induced by ethanol exposure, and knockout of Hmgcs2 with CRISPR/Cas9 attenuated SLC25A5 Kbhb. Together, our study demonstrated a widespread Kbhb landscape under ethanol exposure and clarified a physiological effect of Kbhb modification on liver lipid accumulation.

Clinical utility of polygenic scores for cardiometabolic disease in Arabs.

Arabs account for 5% of the world population and have a high burden of cardiometabolic disease, yet clinical utility of polygenic risk prediction in Arabs remains understudied. Among 5399 Arab patients, we optimize polygenic scores for 10 cardiometabolic traits, achieving a performance that is better than published scores and on par with performance in European-ancestry individuals. Odds ratio per standard deviation (OR per SD) for a type 2 diabetes score was 1.83 (95% CI 1.74-1.92), and each SD of body mass index (BMI) score was associated with 1.18 kg/m2 difference in BMI. Polygenic scores associated with disease independent of conventional risk factors, and also associated with disease severity-OR per SD for coronary artery disease (CAD) was 1.78 (95% CI 1.66-1.90) for three-vessel CAD and 1.41 (95% CI 1.29-1.53) for one-vessel CAD. We propose a pragmatic framework leveraging public data as one way to advance equitable clinical implementation of polygenic scores in non-European populations.