The function of the ATG8 in the cilia and cortical microtubule maintenance of Euplotes amieti.

Autophagy regulates the formation of primary cilia, which in turn affects autophagy. The relationship between autophagy and cilia is known to be bidirectional although the specific mechanisms involved have yet to be elucidated. In this study, we found for the first time that ATG8 protein localizes in the basal body of the dorsal kineties and the base of the ventral cirri in Euplotes amieti. ATG8 protein maintains the structural integrity of cilia and plays a role in the construction of the cortical ciliature and microtubule cytoskeleton associated with cilia. ATG8 gene interference leads to the degradation of IFT88, the transport protein in cilia, thus inhibiting the generation of cilia, and affecting the swing of cilia. This influences the swimming speed and cilia pattern, leading to death in Euplotes amieti.

A nomogram for prediction of ERCP success in patients with bile duct leaks: a multicenter study.

BACKGROUND: Bile duct leaks (BDLs) are serious complications that occurs after hepatobiliary surgery and trauma, leading to rapid clinical deterioration. Endoscopic retrograde cholangiopancreatography (ERCP) is the first-line treatment for BDLs, but it is not clear which patients will respond to this therapy and which patients will require additional surgical intervention. The aim of our study was to explore the predictors of successful ERCP for BDLs. METHODS: A retrospective analysis was conducted using data from six centers' databases. All consecutive patients who were clinically confirmed as BDLs were included in the study. Collected data were demographics, disease severity, and ERCP procedure characteristics. Univariate and multivariate analysis were used to select independent predictive factors that affect the outcome of ERCP for BDLs, and a nomogram was established. Calibration and ROC curves were used to evaluate the models. RESULTS: Four hundred and forty-eight consecutive patients were clinically confirmed as BDLs and 347 were excluded. In the 101 patients included patients, clinical success was achieved in 78 patients (77.2%). In logistic multivariable regression, two independent factors were negatively associated with the success of ERCP: SIRS (OR, 0.183; 95% CI 0.039-0.864; P = 0.032) and high-grade leak (OR 0.073; 95% CI 0.010-0.539; P = 0.010). Two independent factors were positively associated with the success of ERCP: leak-bridging drainage (OR 4.792; 95% CI 1.08-21.21; P = 0.039) and cystic duct leak (OR 6.193; 95% CI 1.03-37.17; P = 0.046). The prediction model with these four factors was evaluated using a receiver-operating characteristic (ROC) curve, which demonstrated an area under the curve of 0.9351. The calibration curve showed that the model had good predictive accuracy. CONCLUSION: Leak-bridging drainage and cystic duct leak are positive predictors for the success of ERCP, while SIRS and high-grade leak are negative predictors. This prediction model with nomogram has good predictive ability and practical clinical value, and may be helpful in clinical decision-making and prognostication.

Metal element-based adsorbents for phosphorus capture: Chaperone effect, performance and mechanism.

Excessive phosphorus (P) enters the water bodies via wastewater discharges or agricultural runoff, triggering serious environmental problems such as eutrophication. In contrast, P as an irreplaceable key resource, presents notable supply-demand contradictions due to ineffective recovery mechanisms. Hence, constructing a system that simultaneously reduce P contaminants and effective recycling has profound theoretical and practical implications. Metal element-based adsorbents, including metal (hydro) oxides, layered double hydroxides (LDHs) and metal-organic frameworks (MOFs), exhibit a significant chaperone effect stemming from strong orbital hybridization between their intrinsic Lewis acid sites and P (Lewis base). This review aims to parse the structure-effect relationship between metal element-based adsorbents and P, and explores how to optimize the P removal properties. Special emphasis is given to the formation of the metal-P chemical bond, which not only depends on the type of metal in the adsorbent but also closely relates to its surface activity and pore structure. Then, we delve into the intrinsic mechanisms behind these adsorbents' remarkable adsorption capacity and precise targeting. Finally, we offer an insightful discussion of the prospects and challenges of metal element-based adsorbents in terms of precise material control, large-scale production, P-directed adsorption and effective utilization.

Unraveling the epigenetic code: human kidney DNA methylation and chromatin dynamics in renal disease development.

Epigenetic changes may fill a critical gap in our understanding of kidney disease development, as they not only reflect metabolic changes but are also preserved and transmitted during cell division. We conducted a genome-wide cytosine methylation analysis of 399 human kidney samples, along with single-nuclear open chromatin analysis on over 60,000 cells from 14 subjects, including controls, and diabetes and hypertension attributed chronic kidney disease (CKD) patients. We identified and validated differentially methylated positions associated with disease states, and discovered that nearly 30% of these alterations were influenced by underlying genetic variations, including variants known to be associated with kidney disease in genome-wide association studies. We also identified regions showing both methylation and open chromatin changes. These changes in methylation and open chromatin significantly associated gene expression changes, most notably those playing role in metabolism and expressed in proximal tubules. Our study further demonstrated that methylation risk scores (MRS) can improve disease state annotation and prediction of kidney disease development. Collectively, our results suggest a causal relationship between epigenetic changes and kidney disease pathogenesis, thereby providing potential pathways for the development of novel risk stratification methods.

Oncolytic Peptide-Nanoplatform Drives Oncoimmune Response and Reverses Adenosine-Induced Immunosuppressive Tumor Microenvironment.

The application of oncolytic peptides has become a powerful approach to induce complete and long-lasting remission in multiple types of carcinomas, as affirmed by the appearance of tumor-associated antigens and adenosine triphosphate (ATP) in large quantities, which jumpstarts the cancer-immunity cycle. However, the ATP breakdown product adenosine is a significant contributor to forming the immunosuppressive tumor microenvironment, which substantially weakens peptide-driven oncolytic immunotherapy. In this study, a lipid-coated micelle (CA@TLM) loaded with a stapled oncolytic peptide (PalAno) and an adenosine 2A receptor (A2AR) inhibitor (CPI-444) is devised to enact tumor-targeted oncolytic immunotherapy and to overcome adenosine-mediated immune suppression simultaneously. The CA@TLM micelle accumulates in tumors with high efficiency, and the acidic lysosomal environment prompts the rapid release of PalAno and CPI-444. Subsequently, PalAno induces swift membrane lysis of tumor cells and the release of antigenic materials. Meanwhile, CPI-444 blocks activation of the immunosuppressive adenosine-A2AR signaling pathway. This combined approach exhibit pronounced synergy at stalling tumor growth and metastasis in animal models for triple-negative breast cancer (TNBC) and melanoma, providing a novel strategy for enhanced oncolytic immunotherapy. This article is protected by copyright. All rights reserved.

Chemical-free vacuum ultraviolet irradiation as ultrafiltration membrane pretreatment technique: Performance, mechanisms and DBPs formation.

Membrane fouling induced by natural organic matter (NOM) has seriously affected the further extensive application of ultrafiltration (UF). Herein, a simple, green and robust vacuum ultraviolet (VUV) technology was adopted as pretreatment before UF and ultraviolet (UV) technology was used for comparison. The results showed that control effect of VUV pretreatment on membrane fouling was better than that of UV pretreatment, as evidenced by the increase of normalized flux from 0.27 to 0.38 and 0.73 after 30 min UV or VUV pretreatment, respectively. This is related to the fact that VUV pretreatment exhibited stronger NOM degradation ability than UV pretreatment owing to the formation of HO•. The steady-state concentration of HO• was calculated as 3.04 × 10-13 M and the cumulative exposure of HO• reached 5.52 × 10-10 M s after 30 min of VUV irradiation. And the second-order rate constant between NOM and HO• was determined as 1.36 × 104 L mg-1 s-1. Furthermore, fluorescence EEM could be applied to predict membrane fouling induced by humic-enriched water. Standard blocking and cake filtration were major fouling mechanisms. Moreover, extension of UV pretreatment time increased the disinfection by-products (DBPs) formation, the DBPs concentration was enhanced from 322.36 to 1187.80 µg/L after 210 min pretreatment. However, VUV pretreatment for 150 min reduced DBPs content to 282.57 µg/L, and DBPs content continued to decrease with the extension of pretreatment time, revealing that VUV pretreatment achieved effective control of DBPs. The variation trend of cytotoxicity and health risk of DBPs was similar to that of DBPs concentration. In summary, VUV pretreatment exhibited excellent effect on membrane fouling alleviation, NOM degradation and DBPs control under a certain pretreatment time.

Simulation of thermal hazards risk in octogen based on non-isothermal DSC data.

To evaluate the possible thermal risks associated with the storage of octogen (HMX), non-isothermal differential scanning calorimetry (DSC) experiments were conducted in order to ascertain the kinetic model and parameters governing its thermal decomposition. DSC measurements indicate that HMX underwent a crystal transformation prior to thermal decomposition. A kinetic model for the autocatalytic thermal decomposition process was developed through the analysis of its primary exothermic peaks. Subsequently, numerical simulations were performed using the aforementioned kinetic model to assess the potential thermal explosion hazard of HMX under two distinct storage conditions. The comparison was made between the models of HMX autocatalytic decomposition temperature and thermal explosion critical temperature under two distinct storage conditions. The prediction of the influence of ambient temperature on the critical temperature of thermal explosion is conducted simultaneously. Finally, the thermal hazard parameters of HMX under different package quality are given.

High-Performance Dual-Responsive Sensing Skin Enabled by Bioinspired Transduction of Coplanar Square-Loop Electrodes.

Advancements in intelligent robots and human-machine interaction necessitate a shift in artificial skins toward multimodal perception. Dual-responsive skins that can detect proximity and pressure information are significant to establishing continuous sensing of interaction processes and extending interactive application scenarios. To address the current limitations of inadequate dual-mode performance, such as limited proximal response change and low tactile sensitivity, this paper presents a bioinspired complementary gradient architecture-enabled (CGA) transduction design and a high-performance dual-responsive skin based on coplanar square-loop electrodes. Through systematic investigation into the transduction of various electrode configurations, comparative results reveal the remarkable potential of coplanar electrodes to deliver superior dual-mode performance without compromise. Simulations and experiments prove that the proposed CGA response mechanism can capture local interface deformation and overall compression signals, further enhancing response sensitivity. The final developed artificial skin is sensitive to external pressure and the approach of objects simultaneously, exhibiting a long detection distance (∼40 mm), a high proximity response (>0.4), and outstanding touch sensitivity (0.131 kPa-1). Furthermore, we demonstrate proof-of-concept applications for the proposed sensing skin in a dual-mode teleoperation interface and adaptive grasping interactions.

Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants.

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.

Polygenic Risk Score Modifies Prostate Cancer Risk of Pathogenic Variants in Men of African Ancestry.

Prostate cancer risk is influenced by rare and common germline variants. We examined the aggregate association of rare germline pathogenic/likely pathogenic/deleterious (P/LP/D) variants in ATM, BRCA2, PALB2, and NBN with a polygenic risk score (PRS) on prostate cancer risk among 1,796 prostate cancer cases (222 metastatic) and 1,424 controls of African ancestry. Relative to P/LP/D non-carriers at average genetic risk (33%-66% of PRS), men with low (0%-33%) and high (66%-100%) PRS had Odds Ratios (ORs) for overall prostate cancer of 2.08 [95% confidence interval (CI) = 0.58-7.49] and 18.06 (95% CI = 4.24-76.84) among P/LP/D carriers and 0.57 (95% CI = 0.46-0.71) and 3.02 (95% CI = 2.53-3.60) among non-carriers, respectively. The OR for metastatic prostate cancer was 2.73 (95% CI = 0.24-30.54) and 28.99 (95% CI = 4.39-191.43) among P/LP/D carriers and 0.54 (95% CI = 0.31-0.95) and 3.22 (95% CI = 2.20-4.73) among non-carriers, for men with low and high PRS, respectively. Lifetime absolute risks of overall prostate cancer increased with PRS (low to high) from 9.8% to 51.5% in P/LP/D carriers and 5.5% to 23.9% in non-carriers. Lifetime absolute risks of metastatic prostate cancer increased with PRS from 1.9% to 18.1% in P/LP/D carriers and 0.3% to 2.2% in non-carriers These findings suggest that assessment of prostate cancer risk for rare variant carriers should include PRS status. SIGNIFICANCE: These findings highlight the importance of considering rare and common variants to comprehensively assess prostate cancer risk in men of African ancestry.

Structure characterization of novel heteropolysaccharides from Pteridium revolutum with antioxidant and antiglycated activities.

This study aims to analysis the structures of polysaccharides isolated from Pteridium revolutum and their antioxidant and antiglycated activities. Three novel water-soluble heteropolysaccharides, named PRP0, PRP1, and PRP2, were isolated from P. revolutum. The average molecular weight was determined by high performance gel permeation chromatography analysis as 1.04 × 106, 8.39 × 105, and 7.37 × 105 Da, respectively. Their structures were characterized using physicochemical and spectroscopic methods. The antioxidant and antiglycated activities were assayed in vitro. PRP0, PRP1, and PRP2 consist of l-Ara, l-Rha, d-Man, d-Xyl, d-Fuc, d-Gal, and d-Glc in different proportions. PRP1 mainly has a backbone of (1 â†’ 3,6)-linked d-Man and (1 â†’ 3)-linked d-Gal on main chain. PRP2 is mainly composed of (1 â†’ 2,4)-linked d-Man and (1 â†’ 3)-linked d-Gal on main chain. All polysaccharides have strong scavenging power on 2,2-difenil-1-picril-hidrazil and hydroxyl radicals and significantly antiglycated activity in Bovine serum albumin-Glucose model, which showing that the polysaccharides have potential application value on the functional food.

[Stapled anoplin peptide combined with photothermal therapy enhances oncolytic immunotherapy of triple-negative breast cancer].

This study constructed a nano-drug delivery system, A3@GMH, by co-delivering the stapled anoplin peptide(Ano-3, A3) with the light-harvesting material graphene oxide(GO), and evaluated its oncolytic immunotherapy effect on triple-negative breast cancer(TNBC). A3@GMH was prepared using an emulsion template method and its physicochemical properties were characterized. The in vivo and in vitro photothermal conversion abilities of A3@GMH were investigated using an infrared thermal imager. The oncoly-tic activity of A3@GMH against TNBC 4T1 cells was evaluated through cell counting kit-8(CCK-8), lactate dehydrogenase(LDH) release, live/dead cell staining, and super-resolution microscopy. The targeting properties of A3@GMH on 4T1 cells were assessed using a high-content imaging system and flow cytometry. In vitro and in vivo studies were conducted to investigate the antitumor mechanism of A3@GMH in combination with photothermal therapy(PTT) through inducing immunogenic cell death(ICD) in 4T1 cells. The results showed that the prepared A3@GMH exhibited distinct mesoporous and coated structures with an average particle size of(308.9±7.5) nm and a surface potential of(-6.79±0.58) mV. The encapsulation efficiency and drug loading of A3 were 23.9%±0.6% and 20.5%±0.5%, respectively. A3@GMH demonstrated excellent photothermal conversion ability and biological safety. A3@GMH actively mediated oncolytic features such as 4T1 cell lysis and LDH release, as well as ICD effects, and showed enhanced in vitro antitumor activity when combined with PTT. In vivo, A3@GMH efficiently induced ICD effects with two rounds of PTT, activated the host's antitumor immune response, and effectively suppressed tumor growth in 4T1 tumor-bearing mice, achieving an 88.9% tumor inhibition rate with no apparent toxic side effects. This study suggests that the combination of stapled anoplin peptide and PTT significantly enhances the oncolytic immunotherapy for TNBC and provides a basis for the innovative application of anti-tumor peptides derived from TCM in TNBC treatment.

Time trends in myopia and high myopia prevalence in young university adults in China.

AIM: To investigate time trends in myopia and high myopia prevalence over 6y among young university adults in China. METHODS: This is a 6-year series cross-sectional study from 2016 to 2021. Totally 4910 freshmen were enrolled and completed a questionnaire concerning age, gender, and disease history. Students with eye diseases were excluded after a detailed eye examination. The refractive status was measured by non-cycloplegic objective refraction and ocular parameters were measured by Lenstar 900. The examination followed the same protocol each year. Trends over time in myopia and high myopia prevalence, as well as ocular biometry parameters, were analyzed. RESULTS: From 2016 to 2021, the axial length (AL) and corneal radius (CR) increased significantly (P=0.002 for AL; P=0.04 for CR). However, the spherical equivalent (SE) and the ratio of axial length to the corneal radius (AL/CR) did not change significantly (P=0.59 for SE; P=0.24 for AL/CR). The frequency of AL ≥26.0 mm increased from 26.6% in 2016 to 29.3% in 2021 (P=0.05 for trend). The prevalence of myopia and high myopia did not change significantly in our study (P≥0.18). Compared to a similar cross-sectional study conducted 10 years ago, the prevalence of myopia decreased significantly (94.9% vs 91.8%, P<0.001). Whereas the prevalence of high myopia increased largely (18.12% vs 27.6%, P<0.001). CONCLUSION: The prevalence of high myopia increases in young university adults during 10y period. Myopia control should begin earlier in childhood. However, these interventions are still needed for high myopia even in young adulthood.

Germline Sequencing Analysis to Inform Clinical Gene Panel Testing for Aggressive Prostate Cancer.

Importance: Germline gene panel testing is recommended for men with advanced prostate cancer (PCa) or a family history of cancer. While evidence is limited for some genes currently included in panel testing, gene panels are also likely to be incomplete and missing genes that influence PCa risk and aggressive disease. Objective: To identify genes associated with aggressive PCa. Design, Setting, and Participants: A 2-stage exome sequencing case-only genetic association study was conducted including men of European ancestry from 18 international studies. Data analysis was performed from January 2021 to March 2023. Participants were 9185 men with aggressive PCa (including 6033 who died of PCa and 2397 with confirmed metastasis) and 8361 men with nonaggressive PCa. Exposure: Sequencing data were evaluated exome-wide and in a focused investigation of 29 DNA repair pathway and cancer susceptibility genes, many of which are included on gene panels. Main Outcomes and Measures: The primary study outcomes were aggressive (category T4 or both T3 and Gleason score ≥8 tumors, metastatic PCa, or PCa death) vs nonaggressive PCa (category T1 or T2 and Gleason score ≤6 tumors without known recurrence), and metastatic vs nonaggressive PCa. Results: A total of 17 546 men of European ancestry were included in the analyses; mean (SD) age at diagnosis was 65.1 (9.2) years in patients with aggressive PCa and 63.7 (8.0) years in those with nonaggressive disease. The strongest evidence of association with aggressive or metastatic PCa was noted for rare deleterious variants in known PCa risk genes BRCA2 and ATM (P ≤ 1.9 × 10-6), followed by NBN (P = 1.7 × 10-4). This study found nominal evidence (P < .05) of association with rare deleterious variants in MSH2, XRCC2, and MRE11A. Five other genes had evidence of greater risk (OR≥2) but carrier frequency differences between aggressive and nonaggressive PCa were not statistically significant: TP53, RAD51D, BARD1, GEN1, and SLX4. Deleterious variants in these 11 candidate genes were carried by 2.3% of patients with nonaggressive, 5.6% with aggressive, and 7.0% with metastatic PCa. Conclusions and Relevance: The findings of this study provide further support for DNA repair and cancer susceptibility genes to better inform disease management in men with PCa and for extending testing to men with nonaggressive disease, as men carrying deleterious alleles in these genes are likely to develop more advanced disease.

Spin Alignment of Vector Mesons in Heavy-Ion Collisions.

Polarized quarks and antiquarks in high-energy heavy-ion collisions can lead to the spin alignment of vector mesons formed by quark coalescence. Using the relativistic spin Boltzmann equation for vector mesons derived from Kadanoff-Baym equations with an effective quark-meson model for strong interaction and quark coalescence model for hadronizaton, we calculate the spin density matrix element ρ_{00} for ϕ mesons and show that anisotropies of local field correlations with respect to the spin quantization direction lead to ϕ meson's spin alignment. We propose that the local correlation or fluctuation of ϕ fields is the dominant mechanism for the observed ϕ meson's spin alignment and its strength can be extracted from experimental data as functions of collision energies. The calculated transverse momentum dependence of ρ_{00} agrees with STAR's data. We further predict the azimuthal angle dependence of ρ_{00} which can be tested in future experiments.

Phase-pure 2D tin halide perovskite thin flakes for stable lasing.

Ruddlesden-Popper tin halide perovskites are a class of two-dimensional (2D) semiconductors with exceptional optoelectronic properties, high carrier mobility, and low toxicity. However, the synthesis of phase-pure 2D tin perovskites is still challenging, and the fundamental understanding of their optoelectronic properties is deficient compared to their lead counterparts. Here, we report the synthesis of a series of 2D tin perovskite bulk crystals with high phase purity via a mixed-solvent strategy. By engineering the quantum-well thickness (related to n value) and organic ligands, the optoelectronic properties, including photoluminescence emission, exciton-phonon coupling strength, and exciton binding energy, exhibit a wide tunability. In addition, these 2D tin perovskites exhibited excellent lasing performance. Both high-n value tin perovskite (n > 1) and n = 1 tin perovskite thin flakes were successfully optically pumped to lase. Furthermore, the lasing from 2D tin perovskites could be maintained up to room temperature. Our findings highlight the tremendous potential of 2D tin perovskites as promising candidates for high-performance lasers.

Rationally designed calcium carbonate multifunctional trap for contaminants adsorption.

Adsorption technology has been widely developed to control environmental pollution, which plays an important role in the sustainable development of modern society. Calcium carbonate (CaCO3) is characterized by its flexible pore design and functional group modification, which meet the high capacity and targeting requirements of adsorption. Therefore, its charm of "small materials for great use" makes it a suitable candidate for adsorption. Firstly, we comprehensively review the research progress of controlled synthesis and surface modification of CaCO3, and its application for adsorbing contaminants from water and air. Then, we systematically examine the structure-effect relationship between CaCO3 adsorbents and contaminants, while also intrinsic mechanism of remarkable capacity and targeted adsorption. Finally, from the perspective of material design and engineering application, we offer insightful discussion on the prospects and challenges of calcium carbonate adsorbents, providing a valuable reference for the further research in this field.

[Analysis and evaluation of bioactive constituents from different parts of Epimedium brevicornum].

A comprehensive analytical method based on ultra-fast liquid chromatography coupled with triple quadrupole/linear ion trap tandem mass spectrometry(UFLC-QTRAP-MS/MS) was established for simultaneous determination of the content of 45 bioactive constituents including flavonoids, alkaloids, amino acids, phenolic acids, and nucleosides in Epimedium brevicornum. The multiple bioactive constituents in leaves, petioles, stems and rhizomes of E. brevicornum were analyzed. The gradient elution was performed at 30 ℃ in an XBridge~® C_(18) column(4.6 mm×100 mm, 3.5 µm) with 0.4% formic acid aqueous solution-acetonitrile as the mobile phase at a flow rate of 0.8 mL·min~(-1). Single factor experiment and response surface methodology were employed to optimize the extraction conditions. Multivariate statistical analyses including systematic cluster analysis(SCA), principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and one-way analysis of variance(One-way ANOVA) were carried out to classify the samples from different parts and identify different constituents. Grey relation analysis(GRA) and entropy weight-TOPSIS analysis were performed to build a multi-index comprehensive evaluation model for different parts of E. brevicornum. The results showed that there was a good relationship between the mass concentrations of 45 constituents and the corresponding peak areas, with the correlation coefficients(r) not less than 0.999 0. The precision, repeatability, and stability of the established method were good for all the target constituents in this study, with the relative standard deviations(RSDs) less than 5.0%(0.62%-4.9%) and the average recovery of 94.51%-105.7%. The above results indicated that the bioactive constituents varied in different parts of E. brevicornum, and the overall quality followed the trend of leaves > petioles > rhizomes > stems. This study verified the rationality of the Chinese Pharmacopoeia(2020 edition) stipulating that the medicinal part of E. brevicornum is the leaf. Moreover, our study indicated that the rhizome had the potential for medicinal development. The established method was accurate and reliable, which can be used to comprehensive evaluate and control the quality of E. brevicornum. This study provides data reference for clarifying the medicinal parts and rationally utilizing the resources of E. brevicornum.

Evaluating Approaches for Constructing Polygenic Risk Scores for Prostate Cancer in Men of African and European Ancestry.

Genome-wide polygenic risk scores (GW-PRS) have been reported to have better predictive ability than PRS based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer risk variants from multi-ancestry GWAS and fine-mapping studies (PRS 269 ). GW-PRS models were trained using a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls used to develop the multi-ancestry PRS 269 . Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California/Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI=0.635-0.677) in African and 0.844 (95% CI=0.840-0.848) in European ancestry men and corresponding prostate cancer OR of 1.83 (95% CI=1.67-2.00) and 2.19 (95% CI=2.14-2.25), respectively, for each SD unit increase in the GW-PRS. However, compared to the GW-PRS, in African and European ancestry men, the PRS 269 had larger or similar AUCs (AUC=0.679, 95% CI=0.659-0.700 and AUC=0.845, 95% CI=0.841-0.849, respectively) and comparable prostate cancer OR (OR=2.05, 95% CI=1.87-2.26 and OR=2.21, 95% CI=2.16-2.26, respectively). Findings were similar in the validation data. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the multi-ancestry PRS 269 constructed with fine-mapping.