A miRNA-7704/IL2RB/AKT feedback loop regulates tumorigenesis and chemoresistance in ovarian cancer.

Ovarian cancer is one of the most common gynecological tumors worldwide. Despite the availability of multiple treatments for ovarian cancer, its resistance to chemotherapy remains a significant challenge. miRNAs play crucial roles in the initiation and progression of cancer by affecting processes such as differentiation, proliferation, and chemoresistance. According to microarray and qPCR analyses, miR-7704 is significantly downregulated in cisplatin-resistant cells compared to parental cells. In this study, we found that miR-7704 inhibited the proliferation and promoted cisplatin sensitivity of ovarian cancer cells in vitro and in vivo. Moreover, ectopic expression of miR-7704 had the same effect as IL2RB knockdown. Further mechanistic studies revealed that miR-7704 played an inhibitory role by regulating IL2RB expression to inactivate the AKT signaling pathway. Furthermore, IL2RB reversed the miR-7704 mediated resistance to cisplatin in ovarian cancer. Based on these findings, miR-7704 and IL2RB show the potential as novel therapeutic targets for ovarian cancer.

Development of an immune-related gene prognostic risk model and identification of an immune infiltration signature in the tumor microenvironment of colon cancer.

BACKGROUND: Colon cancer is a common and highly malignant tumor. Its incidence is increasing rapidly with poor prognosis. At present, immunotherapy is a rapidly developing treatment for colon cancer. The aim of this study was to construct a prognostic risk model based on immune genes for early diagnosis and accurate prognostic prediction of colon cancer. METHODS: Transcriptome data and clinical data were downloaded from the cancer Genome Atlas database. Immunity genes were obtained from ImmPort database. The differentially expressed transcription factors (TFs) were obtained from Cistrome database. Differentially expressed (DE) immune genes were identified in 473 cases of colon cancer and 41 cases of normal adjacent tissues. An immune-related prognostic model of colon cancer was established and its clinical applicability was verified. Among 318 tumor-related transcription factors, differentially expressed transcription factors were finally obtained, and a regulatory network was constructed according to the up-down regulatory relationship. RESULTS: A total of 477 DE immune genes (180 up-regulated and 297 down-regulated) were detected. We developed and validated twelve immune gene models for colon cancer, including SLC10A2, FABP4, FGF2, CCL28, IGKV1-6, IGLV6-57, ESM1, UCN, UTS2, VIP, IL1RL2, NGFR. The model was proved to be an independent prognostic variable with good prognostic ability. A total of 68 DE TFs (40 up-regulated and 23 down-regulated) were obtained. The regulation network between TF and immune genes was plotted by using TF as source node and immune genes as target node. In addition, Macrophage, Myeloid Dendritic cell and CD4+ T cell increased with the increase of risk score. CONCLUSION: We developed and validated twelve immune gene models for colon cancer, including SLC10A2, FABP4, FGF2, CCL28, IGKV1-6, IGLV6-57, ESM1, UCN, UTS2, VIP, IL1RL2, NGFR. This model can be used as a tool variable to predict the prognosis of colon cancer.

Clinical outcomes of parenchymal-sparing versus anatomic resection for colorectal liver metastases: a systematic review and meta-analysis.

BACKGROUND: The advantages of parenchymal-sparing resection (PSR) over anatomic resection (AR) of colorectal liver metastases (CRLM) remain controversial. Here, we aim to evaluate their safety and efficacy. METHODS: A systematic review and meta-analysis of short-term perioperative outcomes and long-term oncological outcomes for PSR and AR were performed by searching Pubmed, Embase, the Cochrane Library and Web of Science databases. RESULTS: Twenty-two studies were considered eligible (totally 7228 patients: AR, n = 3154 (43.6%) vs. PSR, n = 4074 (56.4%)). Overall survival (OS, HR = 1.08, 95% CI: 0.95-1.22, P = 0.245) and disease-free survival (DFS, HR = 1.09, 95% CI: 0.94-1.28, P = 0.259) were comparable between the two groups. There were no significant differences in 3-year OS, 5-year OS, 3-year DFS, 5-year DFS, 3-year liver recurrence-free survival (liver-RFS) and 5-year liver-RFS. In terms of perioperative outcome, patients undergoing AR surgery were associated with prolonged operation time (WMD = 51.48 min, 95% CI: 29.03-73.93, P < 0.001), higher amount of blood loss (WMD = 189.92 ml, 95% CI: 21.39-358.45, P = 0.027), increased intraoperative blood transfusion rate (RR = 2.24, 95% CI: 1.54-3.26, P < 0.001), prolonged hospital stay (WMD = 1.00 day, 95% CI: 0.34-1.67, P = 0.003), postoperative complications (RR = 2.28, 95% CI: 1.88-2.77, P < 0.001), and 90-day mortality (RR = 3.08, 95% CI: 1.88-5.03, P < 0.001). While PSR surgery was associated with positive resection margins (RR = 0.77, 95% CI: 0.61-0.97, P = 0.024), intrahepatic recurrence (RR = 0.90, 95% CI: 0.82-0.98, P = 0.021) and repeat hepatectomy (RR = 0.64, 95% CI: 0.55-0.76, P < 0.001). CONCLUSION: Considering relatively acceptable heterogeneity, PSR had better perioperative outcomes without compromising oncological long-term outcomes. However, these findings must be carefully interpreted, requiring more supporting evidence. TRIAL REGISTRATION: PROSPERO registration number: CRD42023445332.

Modulating the Oxygen Reduction Reaction Performance via Precisely Tuned Reactive Sites in Porphyrin-Based Covalent Organic Frameworks.

Covalent organic frameworks (COFs) have emerged as promising electrocatalysts due to their controllable architectures, highly exposed molecular active sites, and ordered structures. In this study, a series of porphyrin-based COFs (TAPP-x-COF) with various transition metals (Co, Ni, Fe) were synthesized via a facile post-metallization strategy under solvothermal synthesis. The resulting porphyrin-based COFs showed oxygen reduction reaction (ORR) activity with a trend in Co > Fe > Ni. Among them, TAPP-Co-COF exhibited the best ORR activity (E1/2 = 0.66 V and jL = 4.82 mA cm-2) in alkaline media, which is comparable to those of Pt/C under the same conditions. Furthermore, TAPP-Co-COF was employed as a cathode in a Zn-air battery, demonstrating a high power density of 103.73 mW cm-2 and robust cycling stability. This work presents a simple method for using COFs as a smart platform to fabricate efficient electrocatalysts.

Predicting metachronous liver metastasis in patients with colorectal cancer: development and assessment of a new nomogram.

BACKGROUND: We aimed to develop and validate a nomogram model, which could predict metachronous liver metastasis in colorectal cancer within two years after diagnosis. METHODS: A retrospective study was performed on colorectal cancer patients who were admitted to Beijing Shijitan Hospital from January 1, 2016 to June 30, 2019. The least absolute shrinkage and selection operator (LASSO) regression model was used to optimize feature selection for susceptibility to metachronous liver metastasis in colorectal cancer. Multivariable logistic regression analysis was applied to establish a predictive model through incorporating features selected in the LASSO regression model. C-index, receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA) were employed to assess discrimination, distinctiveness, consistency with actual occurrence risk, and clinical utility of candidate predictive model. Internal validation was assessed with bootstrapping method. RESULTS: Predictors contained in candidate prediction nomogram included age, CEA, vascular invasion, T stage, N stage, family history of cancer, and KRAS mutation. This model displayed good discrimination with a C-index of 0.787 (95% confidence interval: 0.728-0.846) and good calibration, whereas area under the ROC curve (AUC) of 0.786. Internal validation obtained C-index of 0.786, and AUC of validation cohort is 0.784. Based on DCA, with threshold probability range from 1 to 60%; this predictive model might identify colorectal cancer metachronous liver metastasis to achieve a net clinical benefit. CONCLUSION: We have developed and validated a prognostic nomogram with good discriminative and high accuracy to predict metachronous liver metastasis in CRC patients.

Primotrapa gen. nov., an extinct transitional genus bridging the evolutionary gap between Lythraceae and Trapoideae, from the early Miocene of North China.

BACKGROUND: Although Trapa is a well-defined genus of distinctive freshwater plants with accumulations of extensive morphological and embryological autapomorphies, its phylogenetic relationships have long been unclear. Formerly placed in the monotypic family Trapaceae, Trapa is now recognized as sister to Sonneratia within Lythraceae s.l., although both genera lack morphological synapomorphies. Thus, a split between the two taxa must have occurred in deep evolutionary time, which raises the possibility of finding transitional forms in the fossil record. RESULTS: Here we describe a new genus and species, Primotrapa weichangensis Y. Li et C.-S. Li (Lythraceae s.l.: Trapoideae), based on three-dimensionally preserved floral cups, fruits, and seeds from the early Miocene of Weichang County, Hebei Province, China. Primotrapa is characterized by a shallow, saucer-shaped floral cup, four distally barbellate sepals, four intersepal appendages alternating with the sepals at the rim of cup, a superior to basally inferior ovary, a fusiform or ovoid, one-seeded fruit with a ribbed surface, and a long persistent peduncle. Two fossil species of Hemitrapa are proposed as new combinations of Primotrapa, namely P. alpina (T. Su et Z.-K. Zhou) Y. Li et C.-S. Li comb. nov. and P. pomelii (Boulay) Y. Li et C.-S. Li comb. nov. Our phylogenetic analysis based on fifteen flower and fruit characters supports the placement of Primotrapa, Hemitrapa and Trapa in a monophyletic clade, which comprise subfamily Trapoideae. The phylogenetic analysis places Primotrapa at the base of Trapoideae. CONCLUSIONS: In view of its superior ovary, which is a plesiomorphic character of Lythraceae s.l., the newly recognized genus Primotrapa and its three species likely represent transitional forms that bridge the evolutionary gap between the basal taxa of Lythraceae s.l., i.e. Lythrum, and the highly derived taxon Trapa.

Feasibility study for evaluating lumbar intervertebral disc degeneration using histogram analysis of T2* values.

PURPOSE: To evaluate the feasibility of histogram analysis of T2* value for the detection and grading of degenerative lumbar intervertebral discs (IVDs) and for the characterization of microstructural heterogeneity of discs. METHODS: Two hundred fourteen lumbar IVDs of 44 subjects with chronic low back pain were examined using sagittal T2WI and axial T2* mapping. All IVDs were classified according to the Pfirrmann grade on T2WI. The correlations between histogram-derived parameters based on T2* values (T2*-HPs) of IVDs and Pfirrmann grade as well as between "red zone ratio" (area of "red zone" on T2* color maps over cross-sectional area of corresponding IVDs) and Pfirrmann grade were calculated. RESULTS: The agreement for Pfirrmann grade of IVDs was excellent (κ = 0.808, P < 0.001). The consistency of the measured T2*-HPs was excellent, with ICCs ranging from 0.828-0.960. Each histogram-derived parameter had a statistically significant relationship with Pfirrmann grade (P < 0.001). The bright "red zone" on T2* color maps of IVDs displayed as a separated peak relative to the rest of voxels in histograms. The mean area ratio of "red zone" over the corresponding IVD was 9.234% ± 6.680 and ranged from 0.517% to 30.598%. The "red zone ratio" was highly related to Pfirrmann grade (r = - 0.732, P < 0.001). CONCLUSION: Histogram analysis of T2* value is an effective tool for the detection and grading of degenerative IVDs. Identification of the "red zone" may provide new breakthroughs in the study of disc degeneration initiation and generate new hypotheses in anatomical and histological studies of IVDs.

Magnetic anisotropy of iridium dimers on two-dimensional materials.

Magnetic dimers with very large magnetic anisotropy have great potential in information storage applications. By using density functional theory calculations (DFT), we systematically investigated the magnetic anisotropy energy (MAE) of bi-iridium (Ir2) dimers on four types of graphene-like two-dimensional (2D) material substrates. We considered four possible adsorption sites for Ir2 on each substrate. The Ir2 dimer prefers to remain at the single vacancy site with the largest binding energy for all the 2D materials considered. The spin moment and MAE of Ir2 can be largely affected by the substrate. On the substrate of germanene, the MAE of Ir2 can be enlarged to approximately 100 meV, even with the higher Ir2 areal density of 1.804 nm-2. Moreover, the direction of the easy magnetization axis is determined by the d states in the vicinity of the Fermi level. The present DFT results can be understood with the help of perturbation theory analysis.

Evolution of atomic structures of SnN, SnN -, and SnNCl- clusters (N = 4-20): Insight from ab initio calculations.

An unbiased global search was employed to explore the low-energy structures of SnN, SnN -, and SnNCl- clusters with N = 4-20 atoms based on the genetic algorithm combined with density functional theory calculations. Some unprecedented low-energy isomers are reported for SnN and SnNCl- clusters. The theoretical electronic properties such as binding energy per atom, ionization potential, adiabatic detachment energy, and vertical detachment energy compare well with the experimental data. Based on the equilibrium structures, the simulated photoelectron spectra are in good agreement with the experimental data in the range of N = 4-20. With addition of a Cl atom on the SnN - cluster, which causes almost no rearrangement on the structural framework, the first peaks in all original photoelectron spectra of SnN - clusters disappear and other peaks nearly retain the original feature at most sizes.

Real-Time Multi-Scale Face Detector on Embedded Devices.

Face detection is the basic step in video face analysis and has been studied for many years. However, achieving real-time performance on computation-resource-limited embedded devices still remains an open challenge. To address this problem, in this paper we propose a face detector, EagleEye, which shows a good trade-off between high accuracy and fast speed on the popular embedded device with low computation power (e.g., the Raspberry Pi 3b+). The EagleEye is designed to have low floating-point operations per second (FLOPS) as well as enough capacity, and its accuracy is further improved without adding too much FLOPS. Specifically, we design five strategies for building efficient face detectors with a good balance of accuracy and running speed. The first two strategies help to build a detector with low computation complexity and enough capacity. We use convolution factorization to change traditional convolutions into more sparse depth-wise convolutions to save computation costs and we use successive downsampling convolutions at the beginning of the face detection network. The latter three strategies significantly improve the accuracy of the light-weight detector without adding too much computation costs. We design an efficient context module to utilize context information to benefit the face detection. We also adopt information preserving activation function to increase the network capacity. Finally, we use focal loss to further improve the accuracy by handling the class imbalance problem better. Experiments show that the EagleEye outperforms the other face detectors with the same order of computation costs, on both runtime efficiency and accuracy.

Role for imaging in spondyloarthritis.

INTRODUCTION: Despite major progress in the imaging diagnosis of spondyloarthritis (SpA), the relative advantages of various available imaging techniques remain unclear. The aim of this study is to assess the current use of imaging in the diagnosis of SpA and to provide suitable recommendations for the use of imaging as an outcome measure as defined in the Assessment in SpondyloArthritis international Society (ASAS) criteria. EVIDENCE ACQUISITION: A systematic literature search regarding imaging in SpA was performed. Articles were assessed by two reviewers to identify and summarized key information pertaining to imaging in SpA. EVIDENCE SYNTHESIS: The search identified 180 relevant articles. Conventional radiography (CR) (17 articles), ultrasound (US) (26 articles), conventional computed tomography (CT) (13 articles), spectral computed tomography (spectral CT) (2 articles), bone scintigraphy (24 articles), and magnetic resonance imaging (MRI) were assessed (98 articles). Sacroiliitis and enthesitis were the major imaging findings in SpA. Multiple studies assessed the feasibility, validity, or differences among imaging modalities for the diagnosis of SpA; however, comprehensive assessments were not available due to a paucity of prospective imaging studies. CR is a widely available, inexpensive initial approach to evaluate patients with suspected SpA. CT enables assessment of structural changes from chronic sacroiliitis including bony erosions, subchondral sclerosis, joint space narrowing, and ankyloses; however, both CR and CT modalities are insensitive for demonstrating early enthesitis and sacroiliitis in SpA. US mainly identifies appendicular enthesitis but is more limited with respect to the sacroiliac joints. Bone scintigraphy can identify sacroiliac joint lesions and semi-quantitatively assess active sacroiliitis. MRI optimally evaluates not only early enthesitis and sacroiliitis of SpA but also chronic structural changes to the sacroiliac joints. CONCLUSIONS: More than one modality may be required for diagnostic and assessment of SpA depending upon disease characteristics and evolution. CR is a suitable initial examination while MRI is able to detect both early and late changes of SpA. A combination of CR and MRI is recommended for the diagnosis and assessment of SpA.

Structures and electronic properties of B3Sin- (n = 4-10) clusters: A combined ab initio and experimental study.

The anionic silicon clusters doped with three boron atoms, B3Sin- (n = 4-10), have been generated by laser vaporization and investigated by anion photoelectron spectroscopy. The vertical detachment energies (VDEs) and adiabatic detachment energies (ADEs) of these anionic clusters are determined. The lowest energy structures of B3Sin- (n = 4-10) clusters are globally searched using genetic algorithm incorporated with density functional theory (DFT) calculations. The photoelectron spectra, VDEs, ADEs of these B3Sin- clusters (n = 4-10) are simulated using B3LYP/6-311+G(d) calculations. Satisfactory agreement is found between theory and experiment. Most of the lowest-energy structures of B3Sin- (n = 4-10) clusters can be derived by using the squashed pentagonal bipyramid structure of B3Si4- as the major building unit. Analyses of natural charge populations show that the boron atoms always possess negative charges, and that the electrons transfer from the 3s orbital of silicon and the 2s orbital of boron to the 2p orbital of boron. The calculated average binding energies, second-order differences of energies, and the HOMO-LUMO gaps show that B3Si6- and B3Si9- clusters have relatively high stability and enhanced chemical inertness. In particular, the B3Si9- cluster with high symmetry (C3v) stands out as an interesting superatom cluster with a magic number of 40 skeletal electrons and a closed-shell electronic configuration of 1S21P61D102S22P61F14 for superatom orbitals.

Structural and magnetic properties of FeGen-/0 (n = 3-12) clusters: Mass-selected anion photoelectron spectroscopy and density functional theory calculations.

The structural, electronic, and magnetic properties of FeGen-/0 (n = 3-12) clusters were investigated by using anion photoelectron spectroscopy in combination with density functional theory calculations. For both anionic and neutral FeGen (n = 3-12) clusters with n ≤ 7, the dominant structures are exohedral. The FeGe8-/0 clusters have half-encapsulated boat-shaped structures, and the opening of the boat-shaped structure is gradually covered by the additional Ge atoms to form Gen cage from n = 9 to 11. The structures of FeGe10-/0 can be viewed as two Ge atoms symmetrically capping the opening of the boat-shaped structure of FeGe8, and those of FeGe12-/0 are distorted hexagonal prisms with the Fe atom at the center. Natural population analysis shows that there is an electron transfer from the Ge atoms to the Fe atom at n = 8-12. The total magnetic moment of FeGen-/0 and local magnetic moment of the Fe atom have not been quenched.

A Visualization System for Interactive Exploration of the Cardiac Anatomy.

Because of the complex and fine structure, visualization of the heart still remains a challenging task, which makes it an active research topic. In this paper, we present a visualization system for medical data, which takes advantage of the recent graphics processing unit (GPU) and can provide real-time cardiac visualization. This work focuses on investigating the anatomical structure visualization of the human heart, which is fundamental to the cardiac visualization, medical training and diagnosis assistance. Several state-of-the-art cardiac visualization methods are integrated into the proposed system and a task specified visualization method is proposed. In addition, auxiliary tools are provided to generate user specified visualization results. The contributions of our work lie in two-fold: for doctors and medical staff, the system can provide task specified visualization with interactive visualization tools; for researchers, the proposed platform can serve as a baseline for comparing different rendering methods and can easily incorporate new rendering methods. Experimental results show that the proposed system can provide favorable cardiac visualization results in terms of both effectiveness and efficiency.

Sequoia maguanensis, a new Miocene relative of the coast redwood, Sequoia sempervirens, from China: implications for paleogeography and paleoclimate.

UNLABELLED: • PREMISE OF THE STUDY: The paleogeographical origin of the relict North American Sequoia sempervirens is controversial. Fossil records indicate a Neogene origin for its foliage characteristics. Although several fossils from the Miocene sediments in eastern Asia have been considered to have close affinities with the modern S. sempervirens, they lack the typical features of a leafy twig bearing linear as well as scale leaves, and the fertile shoots terminating by a cone. The taxonomic status of these fossils has remained unclear.• METHODS: New better-preserved fossils from the upper Miocene of China indicate a new species of Sequoia. This finding not only confirms the former presence of this genus in eastern Asia, but it also confirms the affinity of this Asian form to the modern relict S. sempervirens.• KEY RESULTS: The principal foliage characteristics of S. sempervirens had already originated by the late Miocene. The eastern Asian records probably imply a Beringian biogeographic track of the ancestor of S. sempervirens in the early Neogene, at a time when the land bridge was not too cool for this thermophilic conifer to spread between Asia and North America.• CONCLUSIONS: The climatic context of the new fossil Sequoia in Southeast Yunnan, based on other floristic elements of the fossil assemblage in which it is found, is presumed to be warm and humid. Following the uplift of the Qinghai-Tibet Plateau, this warm, humid climate was replaced by the present monsoonal climate with dry winter and spring. This change may have led to the disappearance of this hygrophilous conifer from eastern Asia.

LeCDJ1, a chloroplast DnaJ protein, facilitates heat tolerance in transgenic tomatoes.

The roles of a tomato (Lycopersicon esculentum) chloroplast-targeted DnaJ protein (LeCDJ1) were investigated using wild-type (WT) and sense transgenic tomatoes. The LeCDJ1 expression was upregulated by 38 °C, 42 °C, 45 °C, NaCl, PEG, methyl viologen (MV) and hydrogen peroxide (H2O2), but not by 30 °C and 35 °C. Meanwhile, LeCDJ1 was involved in the response of plants to abscisic acid (ABA). Under heat stress, the sense plants showed better growth, higher chlorophyll content, lower malondialdehyde (MDA) accumulation and relative electrical conductivity (REC), and also less PSII photoinhibition than WT. Interestingly, the sense plants treated with streptomycin (SM), an inhibitor of organellar translation, still showed higher maximum photochemistry efficiency of PSII (Fv/Fm) and D1 protein levels than the SM-untreated WT, suggesting that the protective effect of LeCDJ1 on PSII was, at least partially, independent of D1 protein synthesis. Furthermore, the relatively lower superoxide radical (O2(•-)) and H2O2 levels in the sense plants were considered to be due to the higher ascorbate peroxidase (APX) and superoxide dismutase (SOD) activity, which seemed unlikely dependent on their transcription level. These results indicated that LeCDJ1 overexpression facilitated heat tolerance in transgenic tomatoes.

Claudin-7 is essential for the maintenance of colonic stem cell homoeostasis via the modulation of Wnt/Notch signalling.

Intestinal stem cells (ISCs) play a crucial role in the continuous self-renewal and recovery of the intestinal epithelium. In previous studies, we have revealed that the specific absence of Claudin-7 (Cldn-7) in intestinal epithelial cells (IECs) can lead to the development of spontaneous colitis. However, the mechanisms by which Cldn-7 maintains homeostasis in the colonic epithelium remain unclear. Therefore, in the present study, we used IEC- and ISC-specific Cldn-7 knockout mice to investigate the regulatory effects of Cldn-7 on colonic Lgr5+ stem cells in the mediation of colonic epithelial injury and repair under physiological and inflammatory conditions. Notably, our findings reveal that Cldn-7 deletion disrupts the self-renewal and differentiation of colonic stem cells alongside the formation of colonic organoids in vitro. Additionally, these Cldn-7 knockout models exhibited heightened susceptibility to experimental colitis, limited epithelial repair and regeneration, and increased differentiation toward the secretory lineage. Mechanistically, we also established that Cldn-7 facilitates the proliferation, differentiation, and organoid formation of Lgr5+ stem cells through the maintenance of Wnt and Notch signalling pathways in the colonic epithelium. Overall, our study provides new insights into the maintenance of ISC function and colonic epithelial homoeostasis.

Identifying molecular subtypes and tumor microenvironment infiltration signatures in kidney renal clear cell carcinoma based on stemness-associated disulfidptosis genes by integrating machine learning, single-cell analyses and experimental validation.

Clear cell renal cell carcinoma (ccRCC) is an aggressive malignant tumor. Disulfidptosis is a new programmed cell death mechanism, which is characterized by the abnormal accumulation of intracellular disulfides that are highly toxic to cells. However, the contribution of disulfidptosis to ccRCC progression has not been fully clarified. In this study, two different molecular subtypes related to disulfidptosis were identified in ccRCC patients by the non-negative matrix factorization (NMF) algorithm. The cluster 1 was characterized by a worse prognosis and higher mRNAsi levels. Then, difference analysis and weighted gene co-expression network analysis (WGCNA) were conducted to search modular genes that are highly associated with tumor stemness and tumor microenvironment. Subsequently, a SADG signature containing nine genes was constructed stepwise by WGCNA and least absolute shrinkage and selection operator (LASSO) Cox regression analysis. The high-risk score group had a worse outcome, and immune regulation and metabolic signatures might be responsible for cancer progression in the high-risk group. After that, a predictive nomogram was constructed, and the predicting power of the risk model was verified using inter and three independent external validation datasets. Nine SADGs were shown to significantly correlate with immune infiltration, tumor mutation burden (TMB), microsatellite instability (MSI) and immune checkpoint. In addition, based on the single-cell RNA sequencing dataset (GSE139555), the distribution and expression of nine hub genes in various types of immune cells were analyzed. Finally, the expression level of the nine genes was verified in clinical samples by qRT-PCR.

Association between Flavonoid Intake and Rheumatoid Arthritis among US Adults.

BACKGROUND: Basic research shows that flavonoids have anti-inflammatory effects that influence rheumatoid arthritis (RA) in rats. Investigating potential dietary interventions for RA helps prevent the onset and progression of the disease. Clinical evidence on the association of- flavonoid and subclass intake with RA is lacking. METHODS: Using three survey cycles of 2007-2008, 2009-2010 and 2017-2018 from the National Health and Nutrition Survey and the United States Department of Agriculture's Food and Nutrient Database for Dietary Studies (FNDDS), we analyzed 7,419 American adults (≥20 years old). The values of flavonoid and subclass intake were calculated using FNDDS. The status questions for self-reported RA were from the NHANES codebook. RESULTS: Weighted analyses, revealed that among the 7,419 participants included in this study (mean age of 44.69 years [standard error, 0.40] and3,584 [48.31%] were female), 408 met the classification criteria for RA. According to the multivariable logistic regression model, compared with the risk of RA in the first quartile (Q1), the risks of RA in the second quartile (Q2), the third quartile (Q3) and the fourth quartile (Q4))were lower (Q2: OR=0.55, 95% CI: 0.38-0.80; Q3: OR=0.66, 95% CI: 0.44-0.97; Q4: OR=0.64, 95% CI: 0.46-0.89;trend: P=0.03). The association between total flavonoids and RA remained significant after full consideration of confounding factors. With regard to the subclasses of flavonoids, high flavanones intake was associated with low RA prevalence in Model 3 (Q3: OR= 0.60, 95% CI:0.39-0.92; Q4: OR = 0.56 95% CI: 0.32-0.99, trend:P =0.02) but no such association was found in the other subclasses. Total flavonoids intake protected against RA, and the risk of developing RA decreased significantly with increasing intake of total flavonoids. CONCLUSION: Total flavonoids and flavanones were significantly associated with reduced RA risk for the American adult population. We highlighted the importance of employing diverse methodologies to assess the health effects of flavonoids.

Titanium Alloy Materials with Very High Cycle Fatigue: A Review.

As the reliability and lifespan requirements of modern equipment continues to escalate, the problems with very high cycle fatigue (VHCF) has obtained increasingly widespread attention, becoming a hot topic in fatigue research. Titanium alloys, which are the most extensively used metal materials in the modern aerospace industry, are particularly prone to VHCF issues. The present study systematically reviewed and summarized the latest (since 2010) developments in VHCF research on titanium alloy, with special focus on the (i) experimental methods, (ii) macroscopic and microscopic characteristics of the fatigue fractures, and (iii) construction of fatigue fracture models. More specifically, the review addresses the technological approaches that were used, mechanisms of fatigue crack initiation, features of the S-N curves and Goodman diagrams, and impact of various factors (such as processing, temperature, and corrosion). In addition, it elucidates the damage mechanisms, evolution, and modeling of VHCF in titanium alloys, thereby improving the understanding of VHCF patterns in titanium alloys and highlighting the current challenges in VHCF research.