Eicosapentaenoic acid-mediated activation of PGAM2 regulates skeletal muscle growth and development via the PI3K/AKT pathway.

Eicosapentaenoic acid regulates glucose uptake in skeletal muscle and significantly affects whole-body energy metabolism. However, the underlying molecular mechanism remains unclear. Here we report that eicosapentaenoic acid activates phosphoglycerate mutase 2, which mediates the conversion of 2-phosphoglycerate into 3-phosphoglycerate. This enzyme plays a pivotal role in glycerol degradation, thereby facilitating the proliferation and differentiation of satellite cells in skeletal muscle. Interestingly, phosphoglycerate mutase 2 inhibits mitochondrial metabolism, promoting the formation of fast-type muscle fibers. Treatment with eicosapentaenoic acid and phosphoglycerate mutase 2 knockdown induced opposite transcriptomic changes, most of which were enriched in the PI3K-AKT signaling pathway. Phosphoglycerate mutase 2 activated the PI3K-AKT signaling pathway, which inhibited the phosphorylation of FOXO1, and, in turn, inhibited mitochondrial function and promoted the formation of fast-type muscle fibers. Our results suggest that eicosapentaenoic acid promotes skeletal muscle growth and regulates glucose metabolism by targeting phosphoglycerate mutase 2 and activating the PI3K/AKT signaling pathway.

Anti-Markovnikov Hydroalkylation of Styrene Derivatives via Hydrazones Catalyzed by Ru-PNP Complex.

A well-defined Ru(II)-PNP complex demonstrated high activity in the anti-Markovnikov hydroalkylation of nonpolarized terminal alkenes via hydrazones. Hydrazone served as a carbanion equivalent to combine with the electrophilic alkene substrate upon activation by the ruthenium catalyst, forming a new C-C bond in a concerted pathway with N2 as the only theoretical byproduct. Experimental and computational studies suggested the existence of a push-pull interaction that activated the alkene for hydrazone addition and then deduced the mechanism.

Application of dual chemotherapeutic drug delivery system based on metal-organic framework platform in enhancing tumor regression for breast cancer research.

The nanomedicine system based on dual drug delivery systems (DDDs) can significantly enhance the efficacy of tumor treatment. Herein, a metal-organic framework, Zeolite imidazole salt frames 8 (ZIF-8), was successfully utilized as a carrier to load the dual chemotherapeutic drugs doxorubicin (DOX) and camptothecin (CPT), named DOX/CPT@ZIF-8 (denoted as DCZ), and their inhibitory effects on 4T1 breast cancer cells were evaluated. The study experimentally demonstrated the synergistic effects of the dual chemotherapeutic drugs within the ZIF-8 carrier and showed that the ZIF-8 nano-carrier loaded with the dual drugs exhibited stronger cytotoxicity and inhibitory effects on 4T1 breast cancer cells compared to single-drug treatment. The use of a ZIF-8-based dual chemotherapeutic drug carrier system highlighted its potential advantages in suppressing 4T1 breast cancer cells.

Identification of different myofiber types in pigs muscles and construction of regulatory networks.

BACKGROUND: Skeletal muscle is composed of muscle fibers with different physiological characteristics, which plays an important role in regulating skeletal muscle metabolism, movement and body homeostasis. The type of skeletal muscle fiber directly affects meat quality. However, the transcriptome and gene interactions between different types of muscle fibers are not well understood. RESULTS: In this paper, we selected 180-days-old Large White pigs and found that longissimus dorsi (LD) muscle was dominated by fast-fermenting myofibrils and soleus (SOL) muscle was dominated by slow-oxidizing myofibrils by frozen sections and related mRNA and protein assays. Here, we selected LD muscle and SOL muscle for transcriptomic sequencing, and identified 312 differentially expressed mRNA (DEmRs), 30 differentially expressed miRNA (DEmiRs), 183 differentially expressed lncRNA (DElRs), and 3417 differentially expressed circRNA (DEcRs). The ceRNA network included ssc-miR-378, ssc-miR-378b-3p, ssc-miR-24-3p, XR_308817, XR_308823, SMIM8, MAVS and FOS as multiple core nodes that play important roles in muscle development. Moreover, we found that different members of the miR-10 family expressed differently in oxidized and glycolytic muscle fibers, among which miR-10a-5p was highly expressed in glycolytic muscle fibers (LD) and could target MYBPH gene mRNA. Therefore, we speculate that miR-10a-5p may be involved in the transformation of muscle fiber types by targeting the MYHBP gene. In addition, PPI analysis of differentially expressed mRNA genes showed that ACTC1, ACTG2 and ACTN2 gene had the highest node degree, suggesting that this gene may play a key role in the regulatory network of muscle fiber type determination. CONCLUSIONS: We can conclude that these genes play a key role in regulating muscle fiber type transformation. Our study provides transcriptomic profiles and ceRNA interaction networks for different muscle fiber types in pigs, providing reference for the transformation of pig muscle fiber types and the improvement of meat quality.

Optimal response to tislelizumab plus chemotherapy in metastatic triple-negative breast cancer: a case report and literature review.

Metastatic triple-negative breast cancer (mTNBC) has the worst prognosis among breast cancer subtypes. Immune checkpoint inhibitors (ICIs) plus chemotherapy have promising survival benefits. Herein, we report a 51-year-old woman whose metastatic lesions were diagnosed as triple-negative subtype and who received tislelizumab plus eribulin treatment and achieved excellent efficacy. To our knowledge, this study is the first attempt to present tislelizumab in combination with eribulin for mTNBC treatment. New treatments resulting in prolonged survival and durable clinical responses would benefit mTNBC patients. Then, we summarize the possible influencing factors of the interaction between tislelizumab and eribulin.

A comparative study on the structure, physical property and halochromic ability of shrimp freshness indicators produced from nine varieties of steamed purple sweet potato.

Nine varieties of purple sweet potato were steamed and used for the production of shrimp freshness indicators. The impact of purple sweet potato's variety on the structure, physical property and halochromic ability of indicators was determined. Results showed different varieties of purple sweet potato had different starch, crude fiber, pectin, protein, fat and total anthocyanin contents. The microstructure, crystallinity, moisture content, water vapor permeability, tensile strength and elongation at break of indicators were affected by crude fiber content in purple sweet potato. The color, transmission and halochromic ability of indicators was associated with the total anthocyanin content in purple sweet potato. Freshness indicators produced from Fuzi No. 1, Ganzi No. 6, Ningzi No. 2, Ningzi No. 4, Qining No. 2 and Qining No. 18 of purple sweet potato were suitable to indicate shrimp freshness. This study provides useful information on screening suitable varieties of purple sweet potato for intelligent packaging.

Denitrification Characteristics of the Low-Temperature Tolerant Denitrification Strain Achromobacter spiritinus HS2 and Its Application.

The low-temperature environment significantly inhibits the growth and metabolism of denitrifying bacteria, leading to an excessive concentration of ammonia nitrogen and total nitrogen in sewage treatment plants during the cold season. In this study, an efficient denitrifying strain of heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria named HS2 was isolated and screened from industrial sewage of a chemical factory in Inner Mongolia at 8 °C. The strain was confirmed to be Achromobacter spiritinus, a colorless rod-shaped bacterium. When cultured with sodium succinate as the carbon source, a carbon-to-nitrogen ratio of 20-30, a shaking rate of 150-180 r/min, and an initial pH of 6-10, the strain HS2 exhibited excellent nitrogen removal at 8 °C. Through the results of whole-genome sequencing, gene amplification, and gas product detection, the strain HS2 was determined to possess key enzyme genes in both nitrification and denitrification pathways, suggesting a HN-AD pathway of NH4+-N → NH2OH → NO2-N → NO → N2O → N2. At 8 °C, the strain HS2 could completely remove ammonia nitrogen from industrial sewage with an initial concentration of 127.23 mg/L. Microbial species diversity analysis of the final sewage confirmed Achromobacter sp. as the dominant genus, which indicated that the low-temperature denitrifying strain HS2 plays an important role in nitrogen removal in actual low-temperature sewage.

Humanistic Health Management and Cancer: Associations of Psychology, Nutrition, and Exercise with Cancer Progression and Pathogenesis.

The incidence rate of cancer is increasing year by year due to the aging of the population, unhealthy living, and eating habits. At present, surgery and medication are still the main treatments for cancer, without paying attention to the impact of individual differences in health management on cancer. However, increasing evidence suggests that individual psychological status, dietary habits, and exercise frequency are closely related to the risk and prognosis of cancer. The reminder to humanity is that the medical concept of the unified treatment plan is insufficient in cancer treatment, and a personalized treatment plan may become a breakthrough point. On this basis, the concept of "Humanistic Health Management" (HHM) is proposed. This concept is a healthcare plan that focuses on self-health management, providing an accurate and comprehensive evaluation of individual lifestyle habits, psychology, and health status, and developing personalized and targeted comprehensive cancer prevention and treatment plans. This review will provide a detailed explanation of the relationship between psychological status, dietary, and exercise habits, and the regulatory mechanisms of cancer. Intended to emphasize the importance of HHM concept in cancer prevention and better prognostic efficacy, providing new ideas for the new generation of cancer treatment.

Genetic dissection and identification of stripe rust resistance genes in the wheat cultivar Lanhangxuan 121, a cultivar selected from a space mutation population.

Stripe rust is a devastating disease of wheat worldwide. Chinese wheat cultivar Lanhangxuan 121 (LHX121), selected from an advanced line L92-47 population that had been subjected to space mutation breeding displayed a consistently higher level of resistance to stipe rust than its parent in multiple field environments. The aim of this research was to establish the number and types of resistance genes in parental lines L92-47 and LHX121 using separate segregating populations. The first population developed from a cross between LHX121 and susceptible cultivar Xinong 822 comprised 278 F2:3 lines. The second validation population comprised 301 F2:3 lines from a cross between L92-47 and susceptible cultivar Xinong 979. Lines of two population were evaluated for stripe rust response at three sites during the 2018-2020 cropping season. Affymetrix 660 K SNP arrays were used to genotype the lines and parents. Inclusive composite interval mapping detected QTL QYrLHX.nwafu-2BS, QYrLHX.nwafu-3BS, and QYrLHX.nwafu-5BS for resistance in all three environments. Based on previous studies and pedigree information, QYrLHX.nwafu-2BS and QYrLHX.nwafu-3BS were likely to be Yr27 and Yr30 that are present in the L92-47 parent. QYrLHX.nwafu-5BS (YrL121) detected only in LHX121 was mapped to a 7.60 cM interval and explained 10.67-22.57% of the phenotypic variation. Compared to stripe rust resistance genes previously mapped to chromosome 5B, YrL121 might be a new adult plant resistance QTL. Furthermore, there were a number of variations signals using 35 K SNP array and differentially expressed genes using RNA-seq between L92-47 and LHX121 in the YrL121 region, indicating that they probably impair the presence and/or function of YrL121. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01461-0.

Europium Metal-Organic Framework with a Tetraphenylethylene-Based Ligand: A Dual-Mechanism Quenching Immunosensor for Enhanced Electrochemiluminescence via the Coordination Trigger.

The effective applications of electrochemiluminescence (ECL) across various fields necessitate ongoing research into novel luminophores and ECL strategies. In this study, self-luminous flower-like nanocomposites (Eu-tcbpe-MOF) were prepared by coordination self-assembly using the aggregation-induced emission material 1,1,2,2-tetrakis(4-carboxyphenyl)ethylene (H4TCBPE) and Eu(III) ions as the precursors. Compared with the monomers and aggregates of H4TCBPE, Eu-tcbpe-MOF exhibits stronger ECL emission. Such enhanced electrochemiluminescence is due to coordination as the coordination-triggered electrochemiluminescence (CT-ECL) enhancement effect. In this study, a cubic-structured nanocomposite (Co9S8@Au@MoS2) was used as an efficient quencher, and a more sensitive ECL detection platform was achieved by two quenching mechanisms: resonance energy transfer and competitive consumption of coreactants. N,N-Diethylethanolamine (DBAE) was used as a coreactant, and DBAE has a faster electron transfer rate and stronger energy supply efficiency than the traditional anodoluminescent coreactant tripropylamine, which effectively improves the ECL signal intensity of Eu-tcbpe-MOF. Hence, a sandwich-type ECL immunosensor was prepared by employing a dual-quenching mechanism, utilizing Eu-tcbpe-MOF as the detection probe and Co9S8@Au@MoS2 as the quencher, achieving precise detection of carcinoembryonic antigen from 0.1 pg·mL-1 to 100 ng·mL-1 with a detection limit of 35.1 fg·mL-1.

Metabolic Engineering of Escherichia coli for High-Titer Biosynthesis of 3'-Sialyllactose.

3'-Sialyllactose (3'-SL) is among the foremost and simplest sialylated breast milk oligosaccharides. In this study, an engineered Escherichia coli for high-titer 3'-SL biosynthesis was developed by introducing a multilevel metabolic engineering strategy, including (1) the introduction of precursor CMP-Neu5Ac synthesis pathway and high-performance α2,3-sialyltransferase (α2,3-SiaT) genes into strain BZ to achieve de novo synthesis of 3'-SL; (2) optimizing the expression of glmS-glmM-glmU involved in the UDP-GlcNAc and CMP-Neu5Ac synthesis pathways, and constructing a glutamine cycle system, balancing the precursor pools; (3) analysis of critical intermediates and inactivation of competitive pathway genes to redirect carbon flux to 3'-SL biosynthesis; and (4) enhanced catalytic performance of rate-limiting enzyme α2,3-SiaT by RBS screening, protein tag cloning. The final strain BZAPKA14 yielded 9.04 g/L 3'-SL in a shake flask. In a 3 L bioreactor, fed-batch fermentation generated 44.2 g/L 3'-SL, with an overall yield and lactose conversion of 0.53 g/(L h) and 0.55 mol 3'-SL/mol, respectively.

Screening of polysaccharides from the differently processed products of Angelica sinensis with the best liver protection effect on chicken and the intervention mechanism study based on tandem mass tag proteomics and multiple reaction monitoring approach.

The incidence of colibacillosis in poultry is on the rise, significantly affecting the chicken industry. Ceftiofur sodium (CS) is frequently employed to treat this disease, resulting in lipopolysaccharide (LPS) buildup. Processing plays a vital role in traditional Chinese veterinary medicine. The potential intervention in liver injury by polysaccharides from the differently processed products of Angelica sinensis (PDPPAS) induced by combined CS and LPS remains unclear. This study aims to investigate the protective effect of PDPPAS on chicken liver injury caused by CS combined with LPS buildup and further identify the polysaccharides with the highest hepatoprotective activity in chickens. Furthermore, the study elucidates polysaccharides' intervention mechanism using tandem mass tag (TMT) proteomics and multiple reaction monitoring (MRM) methods. A total of 190 1-day-old layer chickens were randomly assigned into 12 groups, of which 14 chickens were in the control group and 16 in other groups, for a 10-day trial. The screening results showed that charred A. sinensis polysaccharide (CASP) had the most effective and the best hepatoprotective effect at 48 h. TMT proteomics and MRM validation results demonstrated that the intervention mechanism of the CASP high-dose (CASPH) intervention group was closely related to the protein expressions of FCER2, TBXAS1, CD34, AGXT, GCAT, COX7A2L, and CYP2AC1. Conclusively, the intervention mechanism of CASPH had multitarget, multicenter regulatory features.

Relationship between Serum Indoxyl Sulfate and Klotho Protein and Vascular Calcification in Patients with Chronic Kidney Disease Stages 3-5.

Objective: This study aims to explore the relationships between serum indoxyl sulfate (IS) and Klotho protein levels with vascular calcification in patients with chronic kidney disease (CKD) stages 3-5. Methods: From December 2021 to January 2023, a total of 108 CKD patients in stages 3-5 were enrolled in this cross-sectional investigation. Demographic information and routine clinical biochemistry test results were gathered. Serum levels of IS and Klotho were quantified through enzyme-linked immunosorbent assays. Furthermore, multislice spiral computed tomography was employed to evaluate vascular calcification. The association between serum IS or Klotho levels and abdominal aorta calcification was assessed using univariate analysis and logistic regression analyses. Results: With the progression of CKD stages, serum creatinine, phosphorus, intact parathyroid hormone (iPTH), serum IS, and abdominal aortic calcification exhibited incremental trends, while serum calcium and Klotho protein levels showed a diminishing trend, with statistically significant differences (P < 0.05). Significant differences were observed in age, blood phosphorus, calcium, total parathyroid hormone, serum IS, and Klotho protein levels between patients with and without aortic calcification (P < 0.05). Logistic regression analysis demonstrated that advanced age, high IS level, and low Klotho protein level were independent risk factors for abdominal aortic calcification in CKD patients (P < 0.05). Conclusion: This study indicates elevated serum IS levels and decreased Klotho protein levels in CKD patients. High IS level and low Klotho level were independent risk factors for abdominal aortic calcification.

Experimentally validated design principles of heteroatom-doped-graphene-supported calcium single-atom materials for non-dissociative chemisorption solid-state hydrogen storage.

Non-dissociative chemisorption solid-state storage of hydrogen molecules in host materials is promising to achieve both high hydrogen capacity and uptake rate, but there is the lack of non-dissociative hydrogen storage theories that can guide the rational design of the materials. Herein, we establish generalized design principle to design such materials via the first-principles calculations, theoretical analysis and focused experimental verifications of a series of heteroatom-doped-graphene-supported Ca single-atom carbon nanomaterials as efficient non-dissociative solid-state hydrogen storage materials. An intrinsic descriptor has been proposed to correlate the inherent properties of dopants with the hydrogen storage capability of the carbon-based host materials. The generalized design principle and the intrinsic descriptor have the predictive ability to screen out the best dual-doped-graphene-supported Ca single-atom hydrogen storage materials. The dual-doped materials have much higher hydrogen storage capability than the sole-doped ones, and exceed the current best carbon-based hydrogen storage materials.

Whole genome sequencing enables new genetic diagnosis for inherited retinal diseases by identifying pathogenic variants.

Inherited retinal diseases (IRDs) are a group of common primary retinal degenerative disorders. Conventional genetic testing strategies, such as panel-based sequencing and whole exome sequencing (WES), can only elucidate the genetic etiology in approximately 60% of IRD patients. Studies have suggested that unsolved IRD cases could be attributed to previously undetected structural variants (SVs) and intronic variants in IRD-related genes. The aim of our study was to obtain a definitive genetic diagnosis by employing whole genome sequencing (WGS) in IRD cases where the causative genes were inconclusive following an initial screening by panel sequencing. A total of 271 unresolved IRD patients and their available family members (n = 646) were screened using WGS to identify pathogenic SVs and intronic variants in 792 known ocular disease genes. Overall, 13% (34/271) of IRD patients received a confirmed genetic diagnosis, among which 7% were exclusively attributed to SVs, 4% to a combination of single nucleotide variants (SNVs) and SVs while another 2% were linked to intronic variants. 22 SVs, 3 deep-intronic variants, and 2 non-canonical splice-site variants across 14 IRD genes were identified in the entire cohort. Notably, all of these detected SVs and intronic variants were novel pathogenic variants. Among those, 74% (20/27) of variants were found in genes causally linked to Retinitis Pigmentosa (RP), with the gene EYS being the most frequently affected by SVs. The identification of SVs and intronic variants through WGS enhances the genetic diagnostic yield of IRDs and broadens the mutational spectrum of known IRD-associated genes.

Semi-rationally designed site-saturation mutation of Helicobacter pylori α-1,2-fucosyltransferase for improved catalytic activity and thermostability.

Helicobacter pylori HpfutC, a glycosyltransferase (GT) 11 family glycoprotein, has great potential for industrial 2'-fucosyllactose (2'-FL) production. However, its limited catalytic activity, low expression, and poor thermostability hinder practical applications. Herein, a semi-rationally designed site-saturation mutation was applied to engineer the catalytic activity and thermostability of HpfutC. The 6 single point mutants (K102T, R105C, D115S, Y251F, A255G and K282E) and 6 combined mutants (V1, V2, V3, V4, V5, and V6) with enhanced enzyme activity were obtained by mutant library screening and ordered recombination mutation. The optimal mutant V6, with an optimum temperature of 40 °C, was not a metal-dependent enzyme, yet the reaction was facilitated by Mn2+. Compared to wild-type HpfutC, mutant V6 exhibited a 2.3-fold increase in specific activity and a 2.18-fold increase in half-life at 40 °C, respectively. Kinetic parameters indicated that the Km values of mutant V6 were 34.5 % (lactose) and 25.0 % (GDP-L-fucose) lower than those of the wild enzyme, whereas the kcat/Km values were 1.20 and 1.25-fold higher than those of the wild enzyme. Further, 3D-structure analysis revealed that the highly rigid structure, formation of new hydrogen bonds, increased hydrophobic residues and redistribution of electrostatic charges on the surface may be responsible for the elevated enzyme activity and thermostability. The strategy adopted in this study is of great significance to the solution of the technical bottleneck of HpfutC and the industrial application of 2'-FL.

The relationship between antidepressants and breast cancer: evidence from Mendelian randomization.

BACKGROUND: The use of antidepressants has increased over the years, but the relationship between antidepressant use and the risk of breast cancer is not uniform because of confounding factors. We aimed to assess the effect of antidepressants on breast cancer risk using a two-sample Mendelian randomization (MR) approach.stet METHODS: Secondary data analysis was performed on pooled data from genome-wide association studies based on single-nucleotide polymorphisms that were highly correlated with antidepressants, SSRI drugs, and serotonin and prolactin levels were selected as instrumental variables to evaluate the association between antidepressants and SSRI drugs and prolactin levels with breast cancer and ER+/ER- breast cancer. We then performed a test of the hypothesis that SSRI drugs elevate prolactin concentrations. We performed two-sample Mendelian randomization analyses using inverse variance weighting, MR-Egger regression, and weighted median methods, respectively. RESULTS: There was no significant risk association between antidepressant and SSRI use and the development of breast cancer, ER-positive or ER-negative breast cancer (P > 0.05), and serotonin concentration was not associated with breast cancer risk (P > 0.05). There was a positive causal relationship between prolactin levels and breast cancer (IVW, P = 0.02, OR = 1.058) and ER-positive breast cancer (Weighted median, P = 0.043, OR = 1.141; IVW, P = 0.009, OR = 1.125). Results in SSRI medication and prolactin levels showed no association between SSRI analogs and prolactin levels (P > 0.05). CONCLUSION: Large MR analysis showed that antidepressants as well as SSRI drugs were not associated with breast cancer risk and the SSRI-prolactin-breast cancer hypothesis did not hold in our analysis.

Imaging mRNA in vitro and in vivo with nanofirecracker probes via intramolecular hybridization chain reaction.

Hybridization chain reaction (HCR) based enzyme-free amplification techniques have recently been developed for the visualization of intracellular messenger RNA (mRNA). However, the slow kinetics and potential interference with the intricate biological environments hinder its application in the clinic and in vivo. Herein, we designed a nanofirecracker probe-based strategy using intramolecular hybridization chain reaction (IHCR) amplifier for rapid, efficient, sensitive, specific detection and imaging of survivin mRNA both in vitro and vivo. Two probes, HP1 and HP2, in IHCR were simultaneously incorporated into a DNA nanowire scaffolds to bring HP1 and HP2 to close proximity on the assembled nanowire scaffolds. Empowered by the DNA nanowire scaffolds and spatial confinement effect, the nanofirecracker probe-based IHCR sensing system exhibited improved biostability, accelerated reaction kinetics, and enhanced signal amplification. This new strategy has been successfully applied to imaging mRNA in both cultured cells and in mice. Importantly, this novel sensing method was capable of detecting survivin mRNA in clinical blood samples from subjects with colorectal cancer. Thus, this novel nanofirecracker probe-based IHCR strategy holds great potential in advancing both biomedical research and in molecular diagnostics.

Expansion of human hematopoietic stem cells by inhibiting translation.

Hematopoietic stem cell (HSC) transplantation using umbilical cord blood (UCB) is a potentially life-saving treatment for leukemia and bone marrow failure but is limited by the low number of HSCs in UCB. The loss of HSCs after ex vivo manipulation is also a major obstacle to gene editing for inherited blood disorders. HSCs require a low rate of translation to maintain their capacity for self-renewal, but hematopoietic cytokines used to expand HSCs stimulate protein synthesis and impair long-term self-renewal. We previously described cytokine-free conditions that maintain but do not expand human and mouse HSCs ex vivo. Here we performed a high throughput screen and identified translation inhibitors that allow ex vivo expansion of human HSCs while minimizing cytokine exposure. Transplantation assays show a ~5-fold expansion of long-term HSCs from UCB after one week of culture in low cytokine conditions. Single cell transcriptomic analysis demonstrates maintenance of HSCs expressing mediators of the unfolded protein stress response, further supporting the importance of regulated proteostasis in HSC maintenance and expansion. This expansion method maintains and expands human HSCs after CRISPR/Cas9 editing of the BCL11A+58 enhancer, overcoming a major obstacle to ex vivo gene correction for human hemoglobinopathies.

Machine learning radiomics of magnetic resonance imaging predicts recurrence-free survival after surgery and correlation of LncRNAs in patients with breast cancer: a multicenter cohort study.

BACKGROUND: Several studies have indicated that magnetic resonance imaging radiomics can predict survival in patients with breast cancer, but the potential biological underpinning remains indistinct. Herein, we aim to develop an interpretable deep-learning-based network for classifying recurrence risk and revealing the potential biological mechanisms. METHODS: In this multicenter study, 1113 nonmetastatic invasive breast cancer patients were included, and were divided into the training cohort (n = 698), the validation cohort (n = 171), and the testing cohort (n = 244). The Radiomic DeepSurv Net (RDeepNet) model was constructed using the Cox proportional hazards deep neural network DeepSurv for predicting individual recurrence risk. RNA-sequencing was performed to explore the association between radiomics and tumor microenvironment. Correlation and variance analyses were conducted to examine changes of radiomics among patients with different therapeutic responses and after neoadjuvant chemotherapy. The association and quantitative relation of radiomics and epigenetic molecular characteristics were further analyzed to reveal the mechanisms of radiomics. RESULTS: The RDeepNet model showed a significant association with recurrence-free survival (RFS) (HR 0.03, 95% CI 0.02-0.06, P < 0.001) and achieved AUCs of 0.98, 0.94, and 0.92 for 1-, 2-, and 3-year RFS, respectively. In the validation and testing cohorts, the RDeepNet model could also clarify patients into high- and low-risk groups, and demonstrated AUCs of 0.91 and 0.94 for 3-year RFS, respectively. Radiomic features displayed differential expression between the two risk groups. Furthermore, the generalizability of RDeepNet model was confirmed across different molecular subtypes and patient populations with different therapy regimens (All P < 0.001). The study also identified variations in radiomic features among patients with diverse therapeutic responses and after neoadjuvant chemotherapy. Importantly, a significant correlation between radiomics and long non-coding RNAs (lncRNAs) was discovered. A key lncRNA was found to be noninvasively quantified by a deep learning-based radiomics prediction model with AUCs of 0.79 in the training cohort and 0.77 in the testing cohort. CONCLUSIONS: This study demonstrates that machine learning radiomics of MRI can effectively predict RFS after surgery in patients with breast cancer, and highlights the feasibility of non-invasive quantification of lncRNAs using radiomics, which indicates the potential of radiomics in guiding treatment decisions.