Compound heterozygous with Hb G-Taipei and Hb Lepore-Boston-Washington: An unexpected finding triggered by HbA1c measurement.

Background: Hemoglobin A1c has been widely used to diagnose and monitor diabetes. However, the accuracy of HbA1c analysis can be significantly affected by hemoglobin variants, leading to falsely low or elevated levels and misdiagnosis or inappropriate diabetes management. Case report: In this study, we present the case of a 23-year-old man with undetectable HbA1c levels during his annual checkup by high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE). To investigate the reason for HbA1c absence, Sanger sequencing, multiplex ligation-dependent probe amplification assay (MLPA), long-read single molecule real-time sequencing (SMRT) and MALDI-TOF mass spectrometry (MS) were performed, and the proband was identified as compound heterozygous of ß-thalassemia with Hb G-Taipei (HBB:c.68A > G) and Hb Lepore-Boston-Washington (NG_000007.3:g.63632_71046del). Conclusion: The combination of these molecular technologies including MLPA, long-read SMRT sequencing and MALDI-TOF MS is beneficial for identifying rare hemoglobin variants. This case also provides essential evidence for uncovering the effect of compound heterozygosity for Hb Lepore-Boston-Washington and Hb G-Taipei on hematological phenotypes and HbA1c analysis.

Evaluation of effects from hemoglobin variants on HbA1c measurements by different methods.

OBJECTIVES: The impact of seven hemoglobin variants (Hb Q-Thailand, Hb G-Honolulu, Hb Ube-2, Hb New York, Hb J-Bangkok, Hb G-Coushatta, and Hb E) on the outcome of HbA1c was investigated for six methods by comparing with liquid chromatography-tandem mass spectrometry (LC/MS/MS) reference method. METHODS: Twenty-nine normal and 112 variant samples were measured by LC/MS/MS, Sebia Capillarys 3 TERA, Intelligene Biosystems QuanTOF, Premier Hb9210, Arkray HA-8190V, Bio-Rad D-100, and Tosoh G11, then evaluated for correlation, consistency, and mean relative bias among six methods. The lowest biological variation bias of ±2.8 % was an acceptable standard. RESULTS: All methods showed poor correlation and consistency with LC/MS/MS for Hb E. The unacceptable biases were observed for Capillarys 3 TERA (-14.4 to -3.7 % for Hb Q-Thailand, Hb Ube-2, Hb New York, Hb J-Bangkok and Hb E), QuanTOF (-8.3 to -2.9 % for Hb Ube-2, Hb New York and Hb G-Coushatta), Premier Hb9210 (-18.3 to -3.6 % for Hb Q-Thailand, Hb Ube-2, Hb New York, Hb J-Bangkok and Hb E), HA-8190V variant mode (-17.3 to 6.6 % for Hb G-Honolulu, Hb Ube-2, Hb New York, Hb G-Coushatta and Hb E). All variant samples showed larger biases than ±2.8 % comparing HA-8190V fast mode, D-100, and G11 with LC/MS/MS. CONCLUSIONS: The accuracy of different HbA1c methods was influenced by some Hb variants, especially Hb Ube-2 and Hb New York. Thus, laboratories need to choose appropriate methods to measure HbA1c with different Hb variants.

Fusobacterium nucleatum-induced imbalance in microbiome-derived butyric acid levels promotes the occurrence and development of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) ranks among the most prevalent malignant tumors globally. Recent reports suggest that Fusobacterium nucleatum (F. nucleatum) contributes to the initiation, progression, and prognosis of CRC. Butyrate, a short-chain fatty acid derived from the bacterial fermentation of soluble dietary fiber, is known to inhibit various cancers. This study is designed to explore whether F. nucleatum influences the onset and progression of CRC by impacting the intestinal metabolite butyric acid. AIM: To investigate the mechanism by which F. nucleatum affects CRC occurrence and development. METHODS: Alterations in the gut microbiota of BALB/c mice were observed following the oral administration of F. nucleatum. Additionally, DLD-1 and HCT116 cell lines were exposed to sodium butyrate (NaB) and F. nucleatum in vitro to examine the effects on proliferative proteins and mitochondrial function. RESULTS: Our research indicates that the prevalence of F. nucleatum in fecal samples from CRC patients is significantly greater than in healthy counterparts, while the prevalence of butyrate-producing bacteria is notably lower. In mice colonized with F. nucleatum, the population of butyrate-producing bacteria decreased, resulting in altered levels of butyric acid, a key intestinal metabolite of butyrate. Exposure to NaB can impair mitochondrial morphology and diminish mitochondrial membrane potential in DLD-1 and HCT116 CRC cells. Consequently, this leads to modulated production of adenosine triphosphate and reactive oxygen species, thereby inhibiting cancer cell proliferation. Additionally, NaB triggers the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, blocks the cell cycle in HCT116 and DLD-1 cells, and curtails the proliferation of CRC cells. The combined presence of F. nucleatum and NaB attenuated the effects of the latter. By employing small interfering RNA to suppress AMPK, it was demonstrated that AMPK is essential for NaB's inhibition of CRC cell proliferation. CONCLUSION: F. nucleatum can promote cancer progression through its inhibitory effect on butyric acid, via the AMPK signaling pathway.

Identification of tumor heterogeneity associated with KRAS/TP53 co-mutation status in lung adenocarcinoma based on single-cell RNA sequencing.

Lung cancer stands as the predominant cause of cancer-related mortality globally. Lung adenocarcinoma (LUAD), being the most prevalent subtype, garners extensive attention due to its notable heterogeneity, which significantly influences tumor development and treatment approaches. This research leverages single-cell RNA sequencing (scRNA-seq) datasets to delve into the impact of KRAS/TP53 co-mutation status on LUAD. Moreover, utilizing the TCGA-LUAD dataset, we formulated a novel predictive risk model, comprising seven prognostic genes, through LASSO regression, and subjected it to both internal and external validation sets. The study underscores the profound impact of KRAS/TP53 co-mutational status on the tumor microenvironment (TME) of LUAD. Crucially, KRAS/TP53 co-mutation markedly influences the extent of B cell infiltration and various immune-related pathways within the TME. The newly developed predictive risk model exhibited robust performance across both internal and external validation sets, establishing itself as a viable independent prognostic factor. Additionally, in vitro experiments indicate that MELTF and PLEK2 can modulate the invasion and proliferation of human non-small cell lung cancer cells. In conclusion, we elucidated that KRAS/TP53 co-mutations may modulate TME and patient prognosis by orchestrating B cells and affiliated pathways. Furthermore, we spotlight that MELTF and PLEK2 not only function as prognostic indicators for LUAD, but also lay the foundation for the exploration of innovative therapeutic approaches.

Streptomyces-triggered coordination between rhizosphere microbiomes and plant transcriptome enables watermelon Fusarium wilt resistance.

The use of microbial inoculant is a promising strategy to improve plant health, but their efficiency often faces challenges due to difficulties in successful microbial colonization in soil environments. To this end, the application of biostimulation products derived from microbes is expected to resolve these barriers via direct interactions with plants or soil pathogens. However, their effectiveness and mechanisms for promoting plant growth and disease resistance remain elusive. In this study, we showed that root irrigation with the extracts of Streptomyces ahygroscopicus strain 769 (S769) solid fermentation products significantly reduced watermelon Fusarium wilt disease incidence by 30% and increased the plant biomass by 150% at a fruiting stage in a continuous cropping field. S769 treatment led to substantial changes in both bacterial and fungal community compositions, and induced a highly interconnected microbial association network in the rhizosphere. The root transcriptome analysis further suggested that S769 treatment significantly improved the expression of the MAPK signalling pathway, plant hormone signal transduction and plant-pathogen interactions, particular those genes related to PR-1 and ethylene, as well as genes associated with auxin production and reception. Together, our study provides mechanistic and empirical evidences for the biostimulation products benefiting plant health through coordinating plant and rhizosphere microbiome interaction.

Teadenol B as a Component of Microorganism-Fermented Tea Extract Inhibited Breast Cancers by Promoting Autophagy.

Breast cancer is a significant threat to life and health, which needs more safe and effective drugs to be explored. Teadenol B is a characteristic chemical component of microbial fermented tea. This study discovered that teadenol B could exhibit obvious inhibitory effects on all four different clinical subtype characteristics of breast cancer cells. Proteomic studies show that deoxycytidine triphosphate deaminase (DCTD), which could block DNA synthesis and repair DNA damage, had the most significant and consistent reduction in all four types of breast cancer cells with the treatment of teadenol B. Considering MDA-MB-231 cells exhibit poor clinical prognosis and displayed substantial statistical differences in KEGG pathway enrichment analysis results, we investigated its impact on the size and growth of MDA-MB-231 triple-negative breast tumors transplanted into nude mice and demonstrated that teadenol B significantly suppressed tumor growth without affecting body weight significantly. Finally, we found that the conversion of LC3-I to LC3-II in MDA-MB-231 increased significantly with teadenol B treatment. This proved that teadenol B could be a strong autophagy promotor, which explained the down-regulation of DCTD to some extent and may be the potential mechanism underlying teadenol B's anti-breast cancer effects. This finding provides new evidence for drinking fermented tea to prevent breast cancer and highlights the potential of teadenol B as a novel therapeutic option for breast cancer prevention and treatment, necessitating further investigations to clarify its exact target and the details involved.

NLRP3-mediated periodontal ligament cell pyroptosis promotes root resorption.

AIM: To investigate the mechanisms by which periodontal ligament cells (PDLCs) convert biomechanical stimulation into inflammatory microenvironment inducing root resorption (RR). MATERIALS AND METHODS: RNA sequencing was employed to explore mechanisms in force-inflammatory signal transduction. Then resorption volume, odontoclastic activity, PDLC pyroptotic ratio and NOD-like receptor protein 3 (NLRP3)-mediated pyroptosis pathway activation were analysed under force and pyroptosis inhibition. Further osteoclast formation, macrophage number and transwell polarization demonstrated the effects of PDLC pyroptosis on osteoclastogenesis and M1 polarization. RESULTS: RNA sequencing revealed that NLRP3-mediated PDLC pyroptosis induced by Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NFκB)/NLRP3 pathway may be involved in mechano-inflammatory signal transduction. PDLC pyroptosis under force and the expression of NLRP3-mediated pyroptosis pathway in force-enhanced PDLCs were significantly increased, both in vivo and in vitro. MCC950 administration was sufficient to reduce PDLC pyroptosis and alleviate RR, odontoclast formation and M1 polarization in vivo. Further in vitro exploration showed that MCC950 treatment reduced PDLC force-promoted pyroptosis and blocked NLRP3-mediated pyroptosis pathway. Moreover, by treating THP-1 with force-pretreated PDLCs or supernatants, NLRP3-mediated PDLC pyroptotic released products induced osteoclast formation and M1 polarization. CONCLUSIONS: NLRP3-mediated PDLC pyroptosis promotes RR. PDLCs transmit excessive force into inflammation signals through TLR4/NFκB/NLRP3 pathway, inducing PDLC pyroptosis, which directly promotes odontoclast formation and subsequent RR or promotes M1 polarization to indirectly trigger odontoclastogenesis and RR.

Predictors of Gleason Grading Group Upgrading in Low-Risk Prostate Cancer Patients From Transperineal Biopsy After Radical Prostatectomy.

RATIONALE AND OBJECTIVES: To investigate the predictors of Gleason Grading Group (GGG) upgrading in low-risk prostate cancer (Gleason score=3 + 3) from transperineal biopsy after radical prostatectomy (RP). MATERIALS AND METHODS: The clinical data of 160 patients who underwent transperineal biopsy and RP from January 2017 to December 2022 were retrospectively analyzed. First, univariate and multivariate logistic regression analysis were used to obtain independent predictors of postoperative GGG upgrading. Then receiver operating characteristic curve was used to evaluate the diagnostic efficacy of predictors. Finally, Linear-by-Linear Association test was used to analyze the risk trends of patients in different predictor groups in the postoperative GGG. RESULTS: In this study, there were 81 cases (50.6%) in the GGG concordance group and 79 cases (49.4%) in the GGG upgrading group. Univariate analysis showed age, free/total prostate-specific antigen (f/tPSA), proportion of positive biopsies, positive target of magnetic-resonance imaging (MRI) and positive target of contrast-enhanced ultrasound had significant effects on GGG upgrading (all P < .05). In multivariate logistic regression analysis, age (odds ratio [OR]=1.066, 95%CI=1.007-1.127, P = .027), f/tPSA (OR=0.001, 95%CI=0-0.146, P = .001) and positive target of MRI (OR=3.005, 95%CI=1.353-76.674, P = .007) were independent predictors. The prediction model (area under curve=0.751 P < .001) had higher predictive efficacy than all independent predictors. The proportion of patients in exposed group of different GGG increased with the level of GGG, but decreased in nonexposed group, and the linear trend was significantly different (all P < .001). CONCLUSION: Age, f/tPSA, and positive target of MRI were independent predictors of postoperative GGG upgrading. The predictive model constructed had the best diagnostic efficacy.

Crescent calculator: A webtool enabling objective decision-making for assessment of IgA nephropathy immune activity throughout the disease course.

IgA nephropathy (IgAN) is an immune-mediated glomerulonephritis, posing a challenge for the long-term management. It is crucial to monitor the disease's activity over the disease course. Crescent lesions have been known as an active lesion associated with immune activity. We aimed to develop the Crescent Calculator to aid clinicians in making timely and well-informed decisions throughout the long-term disease course, such as renal biopsies and immunosuppressive therapy. 1,761 patients with biopsy-proven IgAN were recruited from four medical centers in Zhejiang Province, China. 16.9% presented crescent lesions. UPCR, URBC, eGFR and C4 were independently associated with the crescent lesions. By incorporating these variables, the Crescent Calculator was constructed to estimate the likelihood of crescent lesions. The predictor achieved AUC values of over 0.82 in two independent testing datasets. In addition, to fulfill varied clinical needs, multiple classification modes were established. The Crescent Calculator was developed to estimate the risk of crescent lesions for patients with IgAN, assisting clinicians in making timely, objective, and well-informed decisions regarding the need for renal biopsies and more appropriate use of immunosuppressive therapy in patients with IgAN.

Terminal modifications independent cell-free RNA sequencing enables sensitive early cancer detection and classification.

Cell-free RNAs (cfRNAs) offer an opportunity to detect diseases from a transcriptomic perspective, however, existing techniques have fallen short in generating a comprehensive cell-free transcriptome profile. We develop a sensitive library preparation method that is robust down to 100 µl input plasma to analyze cfRNAs independent of their 5'-end modifications. We show that it outperforms adapter ligation-based method in detecting a greater number of cfRNA species. We perform transcriptome-wide characterizations in 165 lung cancer, 30 breast cancer, 37 colorectal cancer, 55 gastric cancer, 15 liver cancer, and 133 cancer-free participants and demonstrate its ability to identify transcriptomic changes occurring in early-stage tumors. We also leverage machine learning analyses on the differentially expressed cfRNA signatures and reveal their robust performance in cancer detection and classification. Our work sets the stage for in-depth study of the cfRNA repertoire and highlights the value of cfRNAs as cancer biomarkers in clinical applications.

Different policies constrained agricultural non-point pollutants emission trading management for water system under interval, fuzzy, and stochastic information.

Formulating suitable policies is essential for resources and environmental management. In this study, an agricultural pollutants emission trading management model driven by water resources and pollutants control is developed to search reasonable policies for agricultural water resources allocation under multiple uncertainties. Random-fuzzy and interval information in water resources system that have directly impact on the effectiveness of management schemes is reflected through interval two-stage stochastic fuzzy-probability programming. The model was root from regional agricultural water resources system in Jining City, China under considering the relationship among effective precipitation, crop water demand, and pollutants emission. Two types policies (water consumption-control and pollutants emission-control) are designed for searching the related interaction on water resources management and water quality improvement. The results indicated that water resources policies would be of water and environmental double benefits, and a large rainfall would reduce irrigation amount from water sources and lead to a larger pollutants emission trading. The results will help for defining scientific and effective water resources protection and management policies and analyzing the related interacted effects on water consumption, pollutants control and system benefit.

Alkaloids from the stems of Fissistigma maclurei Merr. inhibit the proliferation of synoviocytes.

Two new aporphine-derived alkaloids, aporaloids C and D (1 and 2), along with eight known biogenetically related alkaloids (3-10) were isolated from the stems of Fissistigma maclurei Merr. Their structures were elucidated by detailed analysis of NMR, HRESIMS, MS, IR, UV and Optical rotations data. Compounds 1 and 2 represent a rare example of N-methylol aporphine-derived alkaloids from natural sources. The inhibitory effect of all compounds on the proliferation of primary synovial cells was evaluated. Compound 3 showed potent inhibitory effect on the proliferation of synoviocytes with an IC50 value of 4.8 µM. Compounds 1, 2, 6-9 and 10 exhibited moderate inhibitory activity on synoviocytes, with IC50 values of 36.8, 37.1, 31.2 µM, 32.5, 36.3, 36.8 and 18.2 µM, respectively.

Serum human epididymis protein 4 is associated with disease severity in patients with IgA nephropathy.

BACKGROUND: Human epididymis protein 4 (HE4) is a promising tumor biomarker primarily utilized for the detection of ovarian cancer. However, its potential as a novel diagnostic indicator for immunoglobulin A nephropathy (IgAN) remains unknown. The objective of this study was to investigate the feasibility of serum HE4 as a novel biomarker for patients with IgAN. METHODS: This study enrolled a total of 89 hospitalized patients with IgAN at Peking University Shenzhen Hospital between July 2020 and December 2022, along with 60 healthy control subjects matched for sex and age without evidence of comorbidities. Serum HE4 levels were measured using the Abbott Alinity automated immune analyzer, and the correlation between serum HE4 levels and biochemical markers of renal damage as well as clinicopathologic features in IgAN patients were analyzed. RESULTS: In this study, serum HE4 levels were significantly elevated in patients with IgAN compared to healthy controls (116.43 ± 103.61 pmol/L vs. 35.57 ± 9.33 pmol/L, p < 0.001). There was a positive correlation between serum HE4 levels and blood urea nitrogen (r = 0.58, p < 0.001), creatinine (r = 0.73, p < 0.001), cystatin C (r = 0.82, p < 0.001), ß2-microglobulin (r = 0.77, p < 0.001), α1-microglobulin (r = 0.75, p < 0.001), and glomerulosclerosis ratio (r = 0.56, p < 0.001). Conversely, a negative correlation was observed between serum HE4 levels and hemoglobin (r = -0.42, p < 0.001), albumin (r = -0.44, p < 0.001) and estimated glomerular filtration rate (eGFR) (r = -0.83, p < 0.001). In HE4+ IgAN patients, a higher glomerulosclerosis ratio (p < 0.01) and lower eGFR levels (p < 0.001) were observed compared to HE4- patients. Furthermore, patients with higher pathological classification grade also had higher serum HE4 levels. CONCLUSIONS: Serum HE4 levels were significantly associated with both renal function and the pathological classification of patients with IgAN, indicating that HE4 may serve as a promising biomarker for assessing the severity of IgAN.

Identification of Hb Lepore, Hb anti-Lepore, and α-globin gene triplications by long-read single-molecule real-time sequencing.

OBJECTIVES: Hemoglobin (Hb) Lepore and Hb anti-Lepore are infrequent fusion gene variants that result from nonhomologous crossovers during meiosis. Conventional molecular testing methods may face challenges in identifying these variants. During Hb analysis using capillary electrophoresis, we encountered 6 cases with unusual Hb variants. Our aim was to identify the alterations in their globin genes. METHODS: Gap-polymerase chain reaction (PCR), reverse dot-blot assay (RDB), Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and long-read single-molecule real-time (SMRT) sequencing were used to confirm the presence of globin gene alterations. RESULTS: The routine thalassemia gene test kit using the gap-PCR and RDB techniques did not detect common gene variations. Direct sequencing failed to identify any known or unknown globin gene alterations. The MLPA analysis, however, revealed the possible presence of α-globin gene triplications as well as 2 types of fusion gene alterations. Further analysis using long-read SMRT sequencing accurately identified 3 rare gene variations: αααanti-3.7, Hb Lepore-Boston-Washington, and Hb anti-Lepore P-India. CONCLUSIONS: Conventional methods may overlook rare thalassemias or Hb variants. Long-read SMRT sequencing has the potential to identify breakpoints in fusion genes, demonstrating that it is a promising technique for detecting rare thalassemias.

Two new anthraquinone derivatives from Saprosma crassipes H. S. Lo.

Two new anthraquinone derivatives sapranquinones A and B (1 and 2) together with two known biogenetically related anthraquinone derivatives (3 and 4) were isolated from the stems of Saprosma crassipes H. S. Lo. The structures of these compounds were elucidated using comprehensive spectroscopic methods. Compounds 1-4 were evaluated for their antibacterial activities and compounds 1 and 3 had a broad spectrum antibacterial activity against Staphylococcus albus, Escherichia coli, Bacillus cereus, Micrococcus tetragenus, and Micrococcus luteus with MIC values ranging from 1.25 to 5 µg/mL.

Regional bioethanol supply chain optimization with the integration of GIS-MCDM method and quantile-based scenario analysis.

This study presents a novel decision-support framework for the bioethanol supply chain network planning and management under uncertainties. Under the holistic framework, the most suitable sites for biorefineries are first screened out by adopting a GIS-based multi-criteria decision-making approach. Then, a mixed-integer linear programming model combined with quantile-based scenario analysis is developed to determine the strategic planning (i.e. locations and size of biorefineries) and tactical management (i.e. biomass purchasing, feedstock transportation, bioethanol production, and product delivery) under uncertainties. The model can effectively search for reliable solutions under uncertainties and achieve tradeoff solutions with the consideration of decision makers' risk tolerance. The proposed framework is demonstrated through a case study in China. It is suggested to build seven biorefineries with a capacity of 100 million liters in Zhumadian city. Utilizing 41% of local agricultural residues could satisfy the bioethanol requirement in the transportation sector under the E20 policy. However, the estimated production cost of bioethanol in Zhumadian is very high, about 1.11 $/L, which makes it lose cost advantage in the fuel market. Thus, currently, effective subsidies, mandatory energy substitution policies, along other environmental regulatory measures are desired to promote the bioethanol industry development.

The crucial regulatory role of type I interferon in inflammatory diseases.

Type I interferon (IFN-I) plays crucial roles in the regulation of inflammation and it is associated with various inflammatory diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and periodontitis, impacting people's health and quality of life. It is well-established that IFN-Is affect immune responses and inflammatory factors by regulating some signaling. However, currently, there is no comprehensive overview of the crucial regulatory role of IFN-I in distinctive pathways as well as associated inflammatory diseases. This review aims to provide a narrative of the involvement of IFN-I in different signaling pathways, mainly mediating the related key factors with specific targets in the pathways and signaling cascades to influence the progression of inflammatory diseases. As such, we suggested that IFN-Is induce inflammatory regulation through the stimulation of certain factors in signaling pathways, which displays possible efficient treatment methods and provides a reference for the precise control of inflammatory diseases.

A New Hemoglobin Variant: Hb Tangshan [HBA1: c.239C > T, CD79(GCG > GTG)(Ala > Val)] Detected by MALDI-TOF MS.

In this report we decribed a new α-chain variant found during the measurement of hemoglobin A1c (Hb A1c) using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS). MALDI-TOF MS analysis detected an α-chain variant with a mass of 15,155 Da. However, this Hb variant was not detected during Hb A1c measurement by cation-exchange high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE) methods. Sanger sequencing validated the presence of a heterozygous missense mutation [HBA1: c.239C > T, CD79(GCG > GTG)(Ala > Val)]. The observed 28 Da mass difference exactly matches the theoretical mass difference (28 Da) resulting from the substitution of alanine (89.079) with valine (117.133). As this represents the initial documentation of the mutation, we named it Hb Tangshan after the proband's residence.

Quantitative assessment of condylar bone resorption using fused CBCT images: differentiating and diagnosing three distinct groups based on volume and thickness decrease.

OBJECTIVES: To investigate the accuracy of fused CBCT images in diagnosing three distinct groups of bone changes characterized by volume and thickness decrease in patients with temporomandibular joint osteoarthrosis (TMJ OA) during follow-up. METHODS: In this retrospective study, 109 patients (176 TMJs) with TMJ OA were included. Two consecutive CBCT images for the same patient were registered and fused. Then, three image sets were established: without fusion, fused 2D image, and fused 3D image. Three residents randomly and independently evaluated whether there was condylar resorption with the three image sets respectively. The samples diagnosed as condylar resorption by the expert panel were divided into three subgroups according to the volume and thickness decrease calculated after segmentation. The inter- and intraobserver agreement, receiver operating characteristic (ROC), and area under the curve (AUC) evaluated the diagnostic capability for different subgroups. RESULTS: For the volume decrease more than 50 mm3 and thickness decrease more than 1 mm groups, the AUC values for fused image sets were higher than those without fusion (p < 0.01). For the volume decrease within 50 mm3 and thickness decrease within 1 mm groups, the AUC values for fused 2D image sets were higher than the image sets without fusion (p < 0.05), but there was no significant difference between the fused 3D image sets and the image sets without fusion (p = 0.48 for volume decrease, p = 0.37 for thickness decrease). CONCLUSIONS: The fused images can improve the diagnostic accuracy and repeatability for the samples with at least 50 mm3 volume decrease or 1 mm thickness decrease compared with the image groups without fusion.

Leveraging senescence-oxidative stress co-relation to predict prognosis and drug sensitivity in breast invasive carcinoma.

Introduction: Female breast cancer has risen to be the most common malignancy worldwide, causing a huge disease burden for both patients and society. Both senescence and oxidative stress attach importance to cancer development and progression. However, the prognostic roles of senescence and oxidative stress remain obscure in breast cancer. In this present study, we attempted to establish a predictive model based on senescence-oxidative stress co-relation genes (SOSCRGs) and evaluate its clinical utility in multiple dimensions. Methods: SOSCRGs were identified via correlation analysis. Transcriptome data and clinical information of patients with breast invasive carcinoma (BRCA) were accessed from The Cancer Genome Atlas (TCGA) and GSE96058. SVM algorithm was employed to process subtype classification of patients with BRCA based on SOSCRGs. LASSO regression analysis was utilized to establish the predictive model based on SOSCRGs. Analyses of the predictive model with regards to efficacy evaluation, subgroup analysis, clinical association, immune infiltration, functional strength, mutation feature, and drug sensitivity were organized. Single-cell analysis was applied to decipher the expression pattern of key SOSCRGs in the tumor microenvironment. Additionally, qPCR was conducted to check the expression levels of key SOSCRGs in five different breast cancer cell lines. Results: A total of 246 SOSCRGs were identified. Two breast cancer subtypes were determined based on SOSCRGs and subtype 1 showed an active immune landscape. A SOSCRGs-based predictive model was subsequently developed and the risk score was clarified as independent prognostic predictors in breast cancer. A novel nomogram was constructed and exhibited favorable predictive capability. We further ascertained that the infiltration levels of immune cells and expressions of immune checkpoints were significantly influenced by the risk score. The two risk groups were characterized by distinct functional strengths. Sugar metabolism and glycolysis were significantly upregulated in the high risk group. The low risk group was deciphered to harbor PIK3CA mutation-driven tumorigenesis, while TP53 mutation was dominant in the high risk group. The analysis further revealed a significantly positive correlation between risk score and TMB. Patients in the low risk group may also sensitively respond to several drug agents. Single-cell analysis dissected that ERRFI1, ETS1, NDRG1, and ZMAT3 were expressed in the tumor microenvironment. Moreover, the expression levels of the seven SOSCRGs in five different breast cancer cell lines were quantified and compared by qPCR respectively. Conclusion: Multidimensional evaluations verified the clinical utility of the SOSCRGs-based predictive model to predict prognosis, aid clinical decision, and risk stratification for patients with breast cancer.