METTL3 is essential for normal progesterone signaling during embryo implantation via m6A-mediated translation control of progesterone receptor.

Embryo implantation, a crucial step in human reproduction, is tightly controlled by estrogen and progesterone (P4) via estrogen receptor alpha and progesterone receptor (PGR), respectively. Here, we report that N6-methyladenosine (m6A), the most abundant mRNA modification in eukaryotes, plays an essential role in embryo implantation through the maintenance of P4 signaling. Conditional deletion of methyltransferase-like 3 (Mettl3), encoding the m6A writer METTL3, in the female reproductive tract using a Cre mouse line with Pgr promoter (Pgr-Cre) resulted in complete implantation failure due to pre-implantation embryo loss and defective uterine receptivity. Moreover, the uterus of Mettl3 null mice failed to respond to artificial decidualization. We further found that Mettl3 deletion was accompanied by a marked decrease in PGR protein expression. Mechanistically, we found that Pgr mRNA is a direct target for METTL3-mediated m6A modification. A luciferase assay revealed that the m6A modification in the 5' untranslated region (5'-UTR) of Pgr mRNA enhances PGR protein translation efficiency in a YTHDF1-dependent manner. Finally, we demonstrated that METTL3 is required for human endometrial stromal cell decidualization in vitro and that the METTL3-PGR axis is conserved between mice and humans. In summary, this study provides evidence that METTL3 is essential for normal P4 signaling during embryo implantation via m6A-mediated translation control of Pgr mRNA.

Root-to-shoot signaling positively mediates source-sink relation in late growth stages in diploid and tetraploid wheat.

Non-hydraulic root source signaling (nHRS) is a unique positive response to soil drying in the regulation of plant growth and development. However, it is unclear how the nHRS mediates the tradeoff between source and sink at the late growth stages and its adaptive mechanisms in primitive wheat. To address this issue, a root-splitting design was made by inserting solid partition in the middle of the pot culture to induce the occurrence of nHRS using four wheat cultivars (MO1 and MO4, diploid; DM22 and DM31, tetraploid) as materials. Three water treatments were designed as 1) both halves watered (CK), 2) holistic root system watered then droughted (FS), 3) one-half of the root system watered and half droughted (PS). FS and PS were designed to compare the role of the full root system and split root system to induce nHRS. Leaves samples were collected during booting and anthesis to compare the role of nHRS at both growth stages. The data indicated that under PS treatment, ABA concentration was significantly higher than FS and CK, demonstrating the induction of nHRS in split root design and nHRS decreased cytokinin (ZR) levels, particularly in the PS treatment. Soluble sugar and proline accumulation were higher in the anthesis stage as compared to the booting stage. POD activity was higher at anthesis, while CAT was higher at the booting stage. Increased ABA (nHRS) correlated with source-sink relationships and metabolic rate (i.e., leaf) connecting other stress signals. Biomass density showed superior resource acquisition and utilization capabilities in both FS and PS treatment as compared to CK in all plants. Our findings indicate that nHRS-induced alterations in phytohormones and their effect on source-sink relations were allied with the growth stages in primitive wheat.

Piezocatalysis for Chemical-Mechanical Polishing of SiC: Dual Roles of t-BaTiO3 as a Piezocatalyst and an Abrasive.

Chemical mechanical polishing (CMP) offers a promising pathway to smooth third-generation semiconductors. However, it is still a challenge to reduce the use of additional oxidants or/and energy in current CMP processes. Here, a new and green atomically smoothing method: Piezocatalytic-CMP (Piezo-CMP) is reported. Investigation shows that the Piezo-CMP based on tetragonal BaTiO3 (t-BT) can polish the rough surface of a reaction sintering SiC (RS-SiC) to the ultra-smooth surface with an average surface roughness (Ra) of 0.45 nm and the rough surface of a single-crystal 4H-SiC to the atomic planarization Si and C surfaces with Ra of 0.120 and 0.157 nm, respectively. In these processes, t-BT plays a dual role of piezocatalyst and abrasive. That is, it piezo-catalytically generates in-situ active oxygen species to selectively oxidize protruding sites of SiC surface, yielding soft SiO2, and subsequently, it acts as a usual abrasive to mechanically remove these SiO2. This mechanism is further confirmed by density functional theory (DFT) calculation and molecular simulation. In this process, piezocatalytic oxidation is driven only by the original pressure and friction force of a conventional polishing process, thus, the piezo-CMP process do not require any additional oxidant and energy, being a green and effective polishing method.

Defective Tungsten Oxides with Stacking Faults for Proton Exchange Membrane Green-Hydrogen Generation.

Defects can introduce atomic structural modulation and tailor performance of materials. Herein, it demonstrates that semiconductor WO3 with inert electrocatalytic behavior can be activated through defect-induced tensile strains. Structural characterizations reveal that when simply treated in Ar/H2 atmosphere, oxygen vacancies will generate in WO3 and cause defective structures. Stacking faults are found in defects, thus modulating electronic structure and transforming electrocatalytic-inert WO3 into highly active electrocatalysts. Density functional theory (DFT) calculations are performed to calculate *H adsorption energies on various WOx surfaces, revealing the oxygen vacancy composition and strain predicted to optimize the catalytic activity of hydrogen evolution reaction (HER). Such defective tungsten oxides can be integrated into commercial proton exchange membrane (PEM) electrolyser with comparable performance toward Pt-based PEM. This work demonstrates defective metal oxides as promising non-noble metal catalysts for commercial PEM green-hydrogen generation.

Operando Spectroscopy Observation of Mo Clusters-Ti3 C2 TX Catalyst/Support Interface's Dynamic Evolution in Hydrogen Evolution Reaction.

The interaction between catalyst and support plays an important role in electrocatalytic hydrogen evolution (HER), which may explain the improvement in performance by phase transition or structural remodeling. However, the intrinsic behavior of these catalysts (dynamic evolution of the interface under bias, structural/morphological transformation, stability) has not been clearly monitored, while the operando technology does well in capturing the dynamic changes in the reaction process in real time to determine the actual active site. In this paper, nitrogen-doped molybdenum atom-clusters on Ti3 C2 TX (MoACs /N-Ti3 C2 TX ) is used as a model catalyst to reveal the dynamic evolution of MoAcs on Ti3 C2 TX during the HER process. Operando X-ray absorption structure (XAS) theoretical calculation and in situ Raman spectroscopy showed that the Mo cluster structure evolves to a 6-coordinated monatomic Mo structure under working conditions, exposing more active sites and thus improving the catalytic performance. It shows excellent HER performance comparable to that of commercial Pt/C, including an overpotential of 60 mV at 10 mA cm-2 , a small Tafel slope (56 mV dec-1 ), and high activity and durability. This study provides a unique perspective for investigating the evolution of species, interfacial migration mechanisms, and sources of activity-enhancing compounds in the process of electroreduction.

Total Three-Dimensional-Guided Laparoscopic Radical Resection for Left Perihilar Cholangiocarcinoma.

BACKGROUND: The application of three-dimensional (3D) reconstruction has been extensively adopted in hepatectomy navigation,1 yet its utilization in laparoscopic radical resection of perihilar cholangiocarcinoma (pHCCA) remains underexplored. VIDEO: A 54-year-old male patient, classified as Child-Pugh B, presented a small neoplasm situated at the left hepatic duct proximate to the right hepatic and common hepatic ducts. An enhanced abdominal computed tomographic scan identified a solitary lesion measuring 2.8 × 2.4 cm. 3D reconstruction exposed tumor invasion into the left hepatic artery and left portal vein. Given the lesion's unique location, a pure laparoscopic left hepatectomy and caudate lobectomy were executed using a no-touch en block technique post patient consent. Concurrently, extrahepatic bile duct resection, radical lymphadenectomy with skeletonization, and biliary reconstruction were performed. RESULTS: The 3D reconstruction-guided laparoscopic left hepatectomy and caudate lobectomy were successfully completed in 425 min with minimal blood loss (50 mL). The histological grading was T2bN0M0 (stage II). The patient was discharged on the sixth postoperative day without complications, and postoperative treatment included mono-drug chemotherapy with capecitabine. No recurrence was observed at the 6-month follow-up. CONCLUSION: Our experience suggests that 3D reconstruction-guided laparoscopic radical resection may offer increased precision and efficiency in selected pHCCA patients. This approach can potentially yield outcomes comparable with or superior to open surgery, given standardized lymph node dissection by skeletonization, use of the no-touch en block technique, appropriate digestive tract reconstruction, and reduced bleeding and liver damage.

Laparoscopic Left Hepatectomy for Intrahepatic Cholangiocarcinoma.

BACKGROUND: Minimally invasive surgery for intrahepatic cholangiocarcinoma (ICC) remains challenging, especially in advanced patients. PATIENT AND METHOD: A 66-year-old male was diagnosed with stage II ICC after a comprehensive evaluation and was scheduled for laparoscopic exploration and left hepatectomy. RESULTS: The pure laparoscopic left hepatectomy was completed in 240 min, employing a no-touch en bloc technique and lymphadenectomy skeletonization. The patient was discharged 6 days after the operation without any complications and received gemcitabine and cisplatin treatment postoperatively. There was no recurrence during 14 months of follow-up. CONCLUSIONS: Our experience demonstrates that when utilizing the no-touch en bloc technique, standardized lymphadenectomy through skeletonization, and effective control of bleeding, surgeons with extensive expertise in laparoscopic hepatectomy can achieve results comparable to open surgery.

Minimum-Consumption Discrimination of Quantum States via Globally Optimal Adaptive Measurements.

Reducing the average resource consumption is the central quest in discriminating non-orthogonal quantum states for a fixed admissible error rate ϵ. The globally optimal fixed local projective measurement for this task is found to be different from that for previous minimum-error discrimination tasks [S. Slussarenko et al., Phys. Rev. Lett. 118, 030502 (2017)PRLTAO0031-900710.1103/PhysRevLett.118.030502]. To achieve the ultimate minimum average consumption, here we develop a general globally optimal adaptive strategy (GOA) by subtly using the updated posterior probability, which works under any error rate requirements and any one-way measurement restrictions, and can be solved by a convergent iterative relation. First, under the local measurement restrictions, our GOA is solved to serve as the local bound, which saves 16.6 copies (24%) compared with the previously best globally optimal fixed local projective measurement. When the more powerful two-copy collective measurements are allowed, our GOA is experimentally demonstrated to beat the local bound by 3.9 copies (6.0%). By exploiting both adaptivity and collective measurements, our Letter marks an important step toward minimum-consumption quantum state discrimination.

Experimental Demonstration of Inequivalent Mutually Unbiased Bases.

Quantum measurements based on mutually unbiased bases (MUBs) play crucial roles in foundational studies and quantum information processing. It is known that there exist inequivalent MUBs, but little is known about their operational distinctions, not to say experimental demonstration. In this Letter, by virtue of a simple estimation problem, we experimentally demonstrate the operational distinctions between inequivalent triples of MUBs in dimension 4 based on high-precision photonic systems. The experimental estimation fidelities coincide well with the theoretical predictions with only 0.16% average deviation, which is 25 times less than the difference (4.1%) between the maximum estimation fidelity and the minimum estimation fidelity. Our experiments clearly demonstrate that inequivalent MUBs have different information extraction capabilities and different merits for quantum information processing.

Metabolomic profiling of ocular tissues in rabbit myopia: Uncovering differential metabolites and pathways.

To investigate the metabolic difference among tissue layers of the rabbits' eye during the development of myopia using metabolomic techniques and explore any metabolic links or cascades within the ocular wall. Ultra Performance Liquid Chromatography - Mass Spectrometry (UPLC-MS) was utilized for untargeted metabolite screening (UMS) to identify the significant differential metabolites produced between myopia (MY) and control (CT) (horizontal). Subsequently, we compared those key metabolites among tissues (Sclera, Choroid, Retina) of MY for distribution and variation (longitudinal). A total of 6285 metabolites were detected in the three tissues. The differential metabolites were screened and the metabolic pathways of these metabolites in each myopic tissue were labeled, including tryptophan and its metabolites, pyruvate, taurine, caffeine metabolites, as well as neurotransmitters like glutamate and dopamine. Our study suggests that multiple metabolic pathways or different metabolites under the same pathway, might act on different parts of the eyeball and contribute to the occurrence and development of myopia by affecting the energy supply to the ocular tissues, preventing antioxidant stress, affecting scleral collagen synthesis, and regulating various neurotransmitters mutually.

Synthesis, structure, theoretical calculation and antibacterial property of two novel Zn(II)/Ni(II) compounds based on 3, 5-dichlorosalicylaldehyde thiocarbamide ligand.

Two new compounds namely [Zn(L1)phen]31 and Ni(L1)phen(MeOH) 2 (L1 = 3, 5-dichlorosalicylaldehyde thiosemicarbazone) were synthesized by the slow evaporation method at room temperature. The structure of ligand L1 was determined using 1H NMR and 13C NMR spectra. X-ray single crystal diffraction analysis revealed that compounds 1-2 can form 3D supramolecular network structures through π···π stacking and hydrogen bonding interactions. The DFT calculation shows that the coordination of ligand and metal is in good agreement with the experimental results. Hirshfeld surface analysis revealed that H…H and Cl…H interactions were the predominant interactions in compounds 1-2. Energy framework analysis indicated that dispersion energy played a dominant role in the energy composition of compounds 1-2. The inhibitory effects of compounds 1-2 against Escherichia coli (E. coli) and Methicillin-resistant Staphylococcus aureus (MRSA) were tested using the paper disk diffusion method (1: E. coli: 18 mm, MRSA: 17 mm, 2: E. coli: 15 mm, MRSA: 16 mm). Ion releasing experiments were conducted to assess the ion release capacity of compounds 1-2 (Zn2+, 4 days, 38.33 µg/mL; Ni2+, 4 days, 29.12 µg/mL). Molecular docking demonstrated the interaction modes of compounds 1-2 with UDP-N-acetylenolpyruvoylglucosamine reductase (MurB) and dihydrofolate reductase (DHFR) in bacteria, involving hydrophobic, stacking, hydrogen bonding and halogen bonding interactions. The generation of reactive oxygen species (ROS) in bacteria under the presence of compounds 1-2 were evaluated using a fluorescent dye known as dichlorodihydrofluorescein diacetate (DCFH-DA). Potential antibacterial mechanisms of compounds 1-2 were proposed.

Role of ferroptosis and ferroptosis-related long non'coding RNA in breast cancer.

Ferroptosis, a therapeutic strategy for tumours, is a regulated cell death characterised by the increased accumulation of iron-dependent lipid peroxides (LPO). Tumour-associated long non-coding RNAs (lncRNAs), when combined with traditional anti-cancer medicines or radiotherapy, can improve efficacy and decrease mortality in cancer. Investigating the role of ferroptosis-related lncRNAs may help strategise new therapeutic options for breast cancer (BC). Herein, we briefly discuss the genes and pathways of ferroptosis involved in iron and reactive oxygen species (ROS) metabolism, including the XC-/GSH/GPX4 system, ACSL4/LPCAT3/15-LOX and FSP1/CoQ10/NAD(P)H pathways, and investigate the correlation between ferroptosis and LncRNA in BC to determine possible biomarkers related to ferroptosis.

Prognostic value of combined preoperative inflammatory marker neutrophil-lymphocyte ratio and platelet distribution width in patients with gallbladder carcinoma.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) and platelet distribution width (PDW) are associated with poor prognosis in various cancers. We aimed to analyze the prognostic value of the combination of preoperative NLR and PDW in patients with gallbladder carcinoma (GBC). METHODS: A total of 287 GBC patients who underwent curative-intent surgery in our institution was included. The relationship between NLR and PDW and clinicopathological features were analyzed. The receiver operating characteristic (ROC) curves were used to determine the optimal cutoff value for NLR and PDW. Overall survival (OS) was estimated using the Kaplan-Meier method. Meanwhile, the univariate and multivariate Cox regression models were used to assess the risk factors for OS. RESULTS: The optimal cutoff value of NLR and PDW was 3.00 and 14.76, respectively. In addition, survival analysis demonstrated that patients with NLR > 3.00 and PDW > 14.76 had a worse prognosis than patients with NLR ≤ 3.00 and PDW ≤ 14.76, respectively. The multivariate analysis showed that NLR and PDW were independent prognostic factors in the patients with GBC. When we combined NLR and PDW, the area under the ROC curve increased from 0.665 (NLR) and 0.632 (PDW) to 0.676. Moreover, the 1-, 3-, and 5-year OS of group A (patients with NLR ≤ 3.00 and PDW ≤ 14.76), group B (patients with either of NLR > 3.00 or PDW > 14.76) and group C (patients with NLR > 3.00 and PDW > 14.76) were 88.7%, 62.6%, 28.1%, 65.1%, 26.9%, 13.1%, and 34.8%, 8.3%, 0%, respectively. CONCLUSION: The combination of NLR and PDW may serve as a significant prognostic biomarker for GBC patients superior to either NLR or PDW alone.

Expansion of YALIcloneHR toolkit for Yarrowia lipolytica combined with Golden Gate and CRISPR technology.

Metabolic Engineering of yeast is a critical approach to improving the production capacity of cell factories. To obtain genetically stable recombinant strains, the exogenous DNA is preferred to be integrated into the genome. Previously, we developed a Golden Gate toolkit YALIcloneNHEJ, which could be used as an efficient modular cloning toolkit for the random integration of multigene pathways through the innate non-homologous end-joining repair mechanisms of Yarrowia lipolytica. We expanded the toolkit by designing additional building blocks of homologous arms and using CRISPR technology. The reconstructed toolkit was thus entitled YALIcloneHR and designed for gene-specific knockout and integration. To verify the effectiveness of the system, the gene PEX10 was selected as the target for the knockout. This system was subsequently applied for the arachidonic acid production, and the reconstructed strain can accumulate 4.8% of arachidonic acid. The toolkit will expand gene editing technology in Y. lipolytica, which would help produce other chemicals derived from acetyl-CoA in the future.

The volatile organic compounds generated from the Maillard reaction between l-ascorbic acid and l-cysteine in hot compressed water.

BACKGROUND: Hot compressed water (HCW), also known as subcritical water (SCW), refers to high-temperature compressed water in a special physical and chemical state. It is an emerging technology for natural product extraction. The volatile organic compounds (VOCs) generated from the Maillard reaction between l-ascorbic acid (ASA) and l-cysteine (Cys) have attracted significant interest in the flavor and fragrance industry. This study aimed to explore the formation mechanism of VOCs from ASA and Cys and examine the effects of reaction parameters such as temperature, time, and pH in HCW. RESULTS: The identified VOCs were predominantly thiophene derivatives, polysulfides, and pyrazine derivatives in HCW. The findings indicated that thiophene derivatives were formed under various pH conditions, with polysulfide formation favored under acidic conditions and pyrazine derivative formation preferred under weak alkaline conditions, specifically at pH 8.0. CONCLUSION: The Maillard reaction between ASA and Cys mainly produced thiophene derivatives, polysulfides, and pyrazine derivatives in HCW. The generation mechanism was significantly dependent on the surrounding pH conditions. © 2024 Society of Chemical Industry.

Poor healthy lifestyle and life's essential 8 are associated with higher risk of new-onset migraine: a prospective cohort study.

BACKGROUND: Lifestyle are closely related to migraine. However, there is a lack of studies investigating the association between Healthy lifestyle or Life's Essential 8 (LE8) and the risk of migraine. The objective of this research was to investigate the relationship between Healthy lifestyle scores and Life's essential 8 scores, and migraine. METHODS: 332,895 UK Biobank participants without migraine were included. Healthy lifestyle were assessed using seven lifestyle factors, and categorized as poor, intermediate, or ideal. LE8, based on the American Heart Association (AHA) Guidelines for Cardiovascular Health (CVH), consist of eight indicators classified as low, moderate, or high CVH. The Cox proportional hazard model was employed to examine the association between Healthy lifestyle scores, LE8 scores, and migraine, with calculations for population-attributable fraction (PAF) and cumulative incidence. RESULTS: During a median follow-up of 13.58 years, participants in intermediate (HR: 0.91; 95% CI: 0.85, 0.99) or ideal category of Healthy lifestyle (HR: 0.81; 95% CI: 0.73, 0.91) significantly reduced migraine risk compared to the poor category. Similarly, high CVH (HR: 0.73; 95% CI: 0.58, 0.92) also lowered migraine risk, while moderate CVH (HR: 0.93; 95% CI: 0.85, 1.02) did not show a difference compared to low CVH. If all individuals adhered to higher categories of Healthy lifestyle and LE8, approximately 11.38% and 22.05% of migraine cases could be prevented. Among individual lifestyle factors, maintaining an ideal body mass index (BMI), physical activity, sleep duration, sleep pattern, and sedentary time were associated with substantial reductions in migraine risk, by 5.65%, 0.81%, 10.16%, 16.39%, and 6.57%, respectively. CONCLUSION: Our study provides evidence that poor Healthy lifestyle and Life's Essential 8 are associated with higher risk of new-onset migraine.

[Construction of the Framework of a Prediagnostic Risk Assessment System for Outpatient Dental Care]. / å£è ”é—¨è¯Šè¯Šå‰é£Žé™©è¯„ä¼°ä½“ç³»æ¡†æž¶æž„å»ºçš„æŽ¢ç©¶.

Objective: To establish the framework of a prediagnostic risk assessment system for outpatient dental care and to provide references for ensuring patient safety and improving the quality of medical services. Methods: A total of 15 medical workers in a tertiary-care stomatology hospital in Sichuan Province were selected for qualitative interviews between October 2019 and December 2019. On the basis of the results of literature analysis and the interviews, an expert consultation form for prediagnostic risk assessment system for outpatient dental care was developed. Then, consultation of 10 experts in the field of oral health care and nursing was conducted between June 2020 and December 2020. Eventually, the framework of prediagnostic risk assessment system for outpatient dental care was formulated. Results: Four themes emerged from the qualitative interviews. Firstly, prediagnostic risks of dental outpatients involved mainly syncope, cardiovascular emergencies, and other emergency medical risks. Secondly, medical risks came from three sources, patients, healthcare professionals, and the environment. Thirdly, medical professionals of outpatient dental care had limited awareness of the prediagnostic medical risks of patient. Fourthly, medical professionals of outpatient dental care showed inadequate response to and management of the prediagnostic medical risks of patient. The expert consultation helped finalize the Dental Outpatient Prediagnostic Risk Assessment Questionnaire, which included 3 primary indicators (namely, general information, medical history [including history of allergy], and medication assessment), 12 secondary indicators (including patient demographics, patients' status upon admission, oral hygiene habits and special lifestyle habits, sensory disorders, special periods for female patients [ie, menstruation, pregnancy, and breastfeeding], allergy history [history of oral treatment-related allergies], past/present medical history, types of medication, route of medication administration, duration of medication administration, accuracy of medication administration, and adverse drug reactions), and 39 tertiary indicators. The effective recall rate of the expert consultation form was 100%, expert positivity was 100%, and the authority coefficient was 0.83. Kendall's harmony coefficient ranged from 0.808 to 0.839, which was statistically significant (P<0.001). Conclusion: The framework of prediagnosis risk assessment system for outpatient dental care is found to be scientific and specific, but its applicability still needs further validation in clinical practice.

N-Doped Carbon Nanotubes Supported Fe-Mn Dual-Single-Atoms Nanozyme with Synergistically Enhanced Peroxidase Activity for Sensitive Colorimetric Detection of Acetylcholinesterase and Its Inhibitor.

Monitoring acetylcholinesterase (AChE) and its inhibitors is of importance for early diagnosis and therapy of neurological diseases. Herein, N-doped carbon nanotubes supported Fe-Mn dual-single-atoms (FeMn DSAs/N-CNTs) were fabricated by a simple pyrolysis, as thoroughly figured out by a series of the characterization techniques. The peroxidase-like activity of FeMn DSAs/N-CNTs was investigated by catalytic oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to generate rich hydroxyl radicals (·OH) in the H2O2 system, which effectively catalyzed colorless TMB oxidation to blue oxidized TMB (ox-TMB). Besides, the peroxidase-like activity was greatly weakened by thiocholine (derived from AChE), accompanied by making blue ox-TMB fade. Impressively, the highly improved peroxidase-like property is further evidenced by density functional theory (DFT) calculations, where the dual-single atoms show a lower energy barrier (0.079 eV) and their interactions with the N-CNTs played critical roles for producing the oxygen radicals. By virtue of the nanozyme, a low-cost, specific, and sensitive colorimetric sensor was built for detection of AChE with a broader linear range of 0.1-30 U L-1 and a lower limit of detection (LOD, 0.066 U L-1), combined with its feasible analysis in human serum samples. Also, this platform was applied for measuring huperzine A inhibitor with a wide linear scope of 5-500 nM and a LOD down to 4.17 nM. This strategy provides a low-cost and convenient approach for early clinical diagnosis and drug development.

Radiomic signatures reveal multiscale intratumor heterogeneity associated with tissue tolerance and survival in re-irradiated nasopharyngeal carcinoma: a multicenter study.

BACKGROUND: Post-radiation nasopharyngeal necrosis (PRNN) is a severe adverse event following re-radiotherapy for patients with locally recurrent nasopharyngeal carcinoma (LRNPC) and associated with decreased survival. Biological heterogeneity in recurrent tumors contributes to the different risks of PRNN. Radiomics can be used to mine high-throughput non-invasive image features to predict clinical outcomes and capture underlying biological functions. We aimed to develop a radiogenomic signature for the pre-treatment prediction of PRNN to guide re-radiotherapy in patients with LRNPC. METHODS: This multicenter study included 761 re-irradiated patients with LRNPC at four centers in NPC endemic area and divided them into training, internal validation, and external validation cohorts. We built a machine learning (random forest) radiomic signature based on the pre-treatment multiparametric magnetic resonance images for predicting PRNN following re-radiotherapy. We comprehensively assessed the performance of the radiomic signature. Transcriptomic sequencing and gene set enrichment analyses were conducted to identify the associated biological processes. RESULTS: The radiomic signature showed discrimination of 1-year PRNN in the training, internal validation, and external validation cohorts (area under the curve (AUC) 0.713-0.756). Stratified by a cutoff score of 0.735, patients with high-risk signature had higher incidences of PRNN than patients with low-risk signature (1-year PRNN rates 42.2-62.5% vs. 16.3-18.8%, P < 0.001). The signature significantly outperformed the clinical model (P < 0.05) and was generalizable across different centers, imaging parameters, and patient subgroups. The radiomic signature had prognostic value concerning its correlation with PRNN-related deaths (hazard ratio (HR) 3.07-6.75, P < 0.001) and all causes of deaths (HR 1.53-2.30, P < 0.01). Radiogenomics analyses revealed associations between the radiomic signature and signaling pathways involved in tissue fibrosis and vascularity. CONCLUSIONS: We present a radiomic signature for the individualized risk assessment of PRNN following re-radiotherapy, which may serve as a noninvasive radio-biomarker of radiation injury-associated processes and a useful clinical tool to personalize treatment recommendations for patients with LANPC.

Deep-Kcr: accurate detection of lysine crotonylation sites using deep learning method.

As a newly discovered protein posttranslational modification, histone lysine crotonylation (Kcr) involved in cellular regulation and human diseases. Various proteomics technologies have been developed to detect Kcr sites. However, experimental approaches for identifying Kcr sites are often time-consuming and labor-intensive, which is difficult to widely popularize in large-scale species. Computational approaches are cost-effective and can be used in a high-throughput manner to generate relatively precise identification. In this study, we develop a deep learning-based method termed as Deep-Kcr for Kcr sites prediction by combining sequence-based features, physicochemical property-based features and numerical space-derived information with information gain feature selection. We investigate the performances of convolutional neural network (CNN) and five commonly used classifiers (long short-term memory network, random forest, LogitBoost, naive Bayes and logistic regression) using 10-fold cross-validation and independent set test. Results show that CNN could always display the best performance with high computational efficiency on large dataset. We also compare the Deep-Kcr with other existing tools to demonstrate the excellent predictive power and robustness of our method. Based on the proposed model, a webserver called Deep-Kcr was established and is freely accessible at http://lin-group.cn/server/Deep-Kcr.