Neoadjuvant anthracycline followed by toripalimab combined with nab-paclitaxel in patients with early triple-negative breast cancer (NeoTENNIS): a single-arm, phase II study.

Background: Toripalimab, a novel PD-1 antibody, is approved for treatment of multiple solid tumors; however, its neoadjuvant use with chemotherapy for triple-negative breast cancer (TNBC) remains unevaluated. Additionally, induction chemotherapy followed by de-escalation of neoadjuvant immunotherapy remains underexplored. Therefore, we conducted a phase II trial investigating a novel neoadjuvant chemoimmunotherapy regimen including de-escalation of immunotherapy for early-stage TNBC. Methods: Chemotherapy and anti-PD-1 therapy were sequentially administered in a neoadjuvant setting to female patients with histologically confirmed stage II-III TNBC between June 9, 2020, and March 24, 2022. Patients received neoadjuvant therapy with four cycles of epirubicin-cyclophosphamide every 2 weeks, followed by toripalimab (240 mg) every 3 weeks plus nab-paclitaxel weekly for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/is ypN0). Key secondary endpoints included breast pCR (bpCR; ypT0/is), event-free survival and biomarker analysis. Safety was also assessed. This study was registered with ClinicalTrials.gov (NCT04418154). Findings: Among 70 enrolled patients (median age, 51 years; 62.9% stage III), 66 completed treatment without progression and subsequently underwent surgery. The percentages of patients with a tpCR and bpCR were 39 of 70 (55.7%, 95% confidence interval [CI]: 43.3-67.6) and 41 of 70 (58.6%, 95% CI 46.2-70.2), respectively. Sixteen (22.9%) patients experienced grade ≥3 adverse events (AEs), frequently neutropenia (12, 17.1%) and leukopenia (11, 15.7%). The most common immune-related AE was hypothyroidism (5, 7.1%, all grade 1-2). Interpretation: Including 12 weeks of toripalimab in neoadjuvant chemotherapy conferred encouraging activity and manageable toxicity in patients with early TNBC, and this regimen warrants further investigation. Funding: National Natural Science Foundation of China, Junshi Biosciences, and Jiangsu Hengrui Pharmaceuticals.

CTRP6 alleviates endometrial fibrosis by regulating Smad3 pathway in intrauterine adhesion†.

Intrauterine adhesion (IUA) is manifestations of endometrial fibrosis and excessive extracellular matrix deposition. C1q/tumor necrosis factor-related protein-6 (CTRP6) is a newly identified adiponectin paralog which has been reported to modulate the fibrosis process of several diseases; however, the endometrial fibrosis function of CTRP6 remains unknown. Our study aimed to assess the role of CTRP6 in endometrial fibrosis and further explore the underlying mechanism. Here, we found that the expression of CTRP6 was downregulated in the endometrial tissues of IUA. In vitro experiments demonstrated the reduced level of CTRP6 in facilitated transforming growth factor-ß1 (TGF-ß1)-induced human endometrial stromal cells (HESCs). In addition, CTRP6 inhibited the expression of α-smooth muscle actin (α-SMA) and collagen I in TGF-ß1-treated HESCs. Mechanistically, CTRP6 activated the AMP-activated protein kinase (AMPK) and protein kinase B (AKT) pathway in HESCs, and AMPK inhibitor (AraA) or PI3K inhibitor (LY294002) pretreatment abolished the protective effect of CTRP6 on TGF-ß1-induced fibrosis. CTRP6 markedly decreased TGF-ß1-induced Smad3 phosphorylation and nuclear translocation, and AMPK or AKT inhibition reversed these effects. Notably, CTRP6-overexpressing treatment alleviated the fibrosis of endometrium in vivo. Therefore, CTRP6 ameliorates endometrial fibrosis, among which AMPK and AKT are essential for the anti-fibrotic effect of CTRP6 via the Smad3 pathway. Taken together, CTRP6 may be a potential therapeutic target for the treatment of intrauterine adhesion.

The diagnostic performance of T1 mapping in the assessment of breast lesions: A preliminary study.

PURPOSE: To assess T1 mapping performance in distinguishing between benign and malignant breast lesions and to explore its correlation with histopathologic features in breast cancer. METHODS: This study prospectively enrolled 103 participants with a total of 108 lesions, including 25 benign and 83 malignant lesions. T1 mapping, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE) were performed. Two radiologists independently outlined the ROIs and analyzed T1 and apparent diffusion coefficient (ADC) values for each lesion, assessing interobserver reliability with the intraclass correlation coefficient (ICC). T1 and ADC values were compared between benign and malignant lesions, across different histopathological characteristics (histological grades, estrogen, progesterone and HER2 receptors expression, Ki67, N status). Receiver operating characteristic (ROC) analysis and Pearson correlation coefficient (ρ) were performed. RESULTS: T1 values showed statistically significant differences between benign and malignant groups (P < 0.001), with higher values in the malignant (1817.08 ms ± 126.64) compared to the benign group (1429.31 ms ± 167.66). In addition, T1 values significantly increased in the ER (-) group (P = 0.001). No significant differences were found in T1 values among HER2, Ki67, N status, and histological grades groups. Furthermore, T1 values exhibited a significant correlation (ρ) with ER (P < 0.01) and PR (P = 0.03). The AUC for T1 value in distinguishing benign from malignant lesions was 0.69 (95 % CI: 0.55 - 0.82, P = 0.005), and for evaluating ER status, it was 0.75 (95 % CI: 0.62 - 0.87, P = 0.002). CONCLUSIONS: T1 mapping holds the potential as an imaging biomarker to assist in the discrimination of benign and malignant breast lesions and assessing the ER expression status in breast cancer.

Case report: [18F]FAPI-42 PET/CT visualize primary adenoid cystic carcinoma not detected by [18F]FDG.

Adenoid cystic carcinoma (ACC) is a rare salivary gland cancer. Still, its growth and invasion progress is slow, and its hematogenous metastasis is ACC's most common distant metastasis. Because of the broad expression and low background uptake of fibroblast activation protein (FAP) in tumor stroma, FAPI is considered another potential tracer of ACC in addition to FDG. In this case, we report a patient who was diagnosed with metastatic ACC liver cancer by fine needle aspiration biopsy (FNAB) and underwent PET/CT examination of [18F]FDG and [18F]FAPI-42 to find the primary cancer lesion. Finally, the primary cancer lesion was found in the left submandibular gland and was pathologically confirmed as ACC after resection.

Effect of obstructive sleep apnea on in vitro fertilization outcomes in women with polycystic ovary syndrome.

STUDY OBJECTIVES: Polycystic ovary syndrome (PCOS) confers a high risk of obstructive sleep apnea (OSA). Here we investigated the effect of OSA on first in vitro fertilization (IVF) cycle metrics and outcomes in patients with PCOS. METHODS: This was a prospective cohort study of patients with PCOS undergoing their first IVF at a single tertiary center between October 1, 2021, and September 30, 2022. Patients were screened for OSA before IVF and grouped accordingly. Clinical and IVF cycle data were compared between groups. RESULTS: OSA was found in 37.2% of 156 patients with PCOS, with longer infertility duration (4.3 ± 2.5 vs. 3.4 ± 2.0 years) and lower levels of anti-Müllerian and luteinizing hormones than patients without OSA (6.44 ± 2.96 vs 8.69 ± 4.03 µg/L and 6.30 ± 5.02 vs 8.46 ± 6.09 U/L). Antral follicle count was lower in patients with OSA (28.9 ± 12.4 vs 33.2 ± 12.9). During ovarian stimulation, patients with OSA required significantly higher doses of gonadotropin (2080.8 ± 1008.7 vs 1682.8 ± 619.9 U) and had lower peak estradiol level (4473.5 ± 2693.0 vs 5455.7 ± 2955.1 pmol/L) and fewer retrieved oocytes, high-quality, and available embryos (17.8 ± 7.2 vs 21.9 ± 10.5, 4.5 ± 4.4 vs 6.2 ± 4.6, 5.2 ± 4.3 vs 7.4 ± 5.0). Eleven patients were excluded for having no embryos or missing transfer. Therefore, we analyzed the outcome of the first embryo transfer in 145 patients. The biochemical and clinical pregnancy rates were lower in patients with OSA than patients without OSA (51.9% vs 66.7% and 42.3% vs 60.2%). OSA was independently associated with clinical pregnancy rate after controlling for several confounders (P = .043). CONCLUSIONS: OSA impairs female fertility in patients with polycystic ovary syndrome, suggesting an adverse effect on in vitro fertilization cycle stimulation characteristics and clinical outcomes. CITATION: Zhang Q, Wang Z, Ding J, et al. Effect of obstructive sleep apnea on in vitro fertilization outcomes in women with polycystic ovary syndrome. J Clin Sleep Med. 2024;20(1):31-38.

Breast-lesion assessment using amide proton transfer-weighted imaging and dynamic contrast-enhanced MR imaging.

BACKGROUND: Previous studies have indicated that amide proton transfer-weighted imaging (APTWI) could be utilized for differentiating benign and malignant tumors. The APTWI technology has increasingly being applied to breast tumor research in recent years. However, according to the latest literature retrieval, no relevant previous studies compared the value of APTWI and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in distinguishing benign lesions from malignant lesions. In the present study, the application of APTWI and DCE for differentiating the benign and malignant breast lesions was investigated. PATIENTS AND METHODS: APTWI was performed on 40 patients (42 lesions) who were enrolled in this prospective study. The lesions were split into two groups, one with malignant breast lesions (n = 28) and the other with benign breast lesions (n = 14), based on the results of the histology. The measured image characteristics (APT value, apparent diffusion coefficient [ADC] value, and time-of-intensity-curve [TIC] type) were compared between the two groups, and the ROC curve was used to quantify the diagnostic performance on the basis of these factors. The correlation between the APT values and the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 expression levels and histological grades was examined using Spearman's correlation coefficient. RESULTS: The measured APT and ADC values showed a strong inter-observer agreement according to the intraclass correlation coefficients (0.954 and 0.825). Compared to benign lesions, malignant lesions had significantly higher APT values (3.18 ± 1.07 and 2.01 ± 0.51, p < 0.001). Based on APTWI, DCE, diffusion-weighted imaging (DWI), and ADC + APTWI, ADC + DCE, and DCE + APTWI, the area-under-the-curve values were 0.915, 0.815, 0.878, 0.921, 0.916, and 0.936, respectively. CONCLUSIONS: APTWI is a potentially promising method in differentiating benign and malignant breast lesions, and may it become a great substitute for DCE examination in the future.

Nanocomposites based on nanoceria regulate the immune microenvironment for the treatment of polycystic ovary syndrome.

The immune system is closely associated with the pathogenesis of polycystic ovary syndrome (PCOS). Macrophages are one of the important immune cell types in the ovarian proinflammatory microenvironment, and ameliorate the inflammatory status mainly through M2 phenotype polarization during PCOS. Current therapeutic approaches lack efficacy and immunomodulatory capacity, and a new therapeutic method is needed to prevent inflammation and alleviate PCOS. Here, octahedral nanoceria nanoparticles with powerful antioxidative ability were bonded to the anti-inflammatory drug resveratrol (CeO2@RSV), which demonstrates a crucial strategy that involves anti-inflammatory and antioxidative efficacy, thereby facilitating the proliferation of granulosa cells during PCOS. Notably, our nanoparticles were demonstrated to possess potent therapeutic efficacy via anti-inflammatory activities and effectively alleviated endocrine dysfunction, inflammation and ovarian injury in a dehydroepiandrosterone (DHEA)-induced PCOS mouse model. Collectively, this study revealed the tremendous potential of the newly developed nanoparticles in ameliorating the proinflammatory microenvironment and promoting the function of granulosa cells, representing the first attempt to treat PCOS by using CeO2@RSV nanoparticles and providing new insights in combating clinical PCOS.

LncRNA AOC4P recruits TRAF6 to regulate EZH2 ubiquitination and participates in trophoblast glycolysis and M2 macrophage polarization which is associated with recurrent spontaneous abortion.

During embryo implantation, trophoblast cells rely on large amounts of energy produced by glycolysis for their rapid growth and invasion. The disorder of trophoblast metabolism may lead to recurrent spontaneous abortion (RSA). Lactate, which is produced by the glycolysis of trophoblast cells during early pregnancy, can promote the polarization of M2 macrophages and maintain an anti-inflammatory environment at the maternal-fetal interface. Our study found that amine oxidase copper-containing 4 pseudogene (AOC4P) was abnormally increased in villi from RSA patients. It inhibited the glycolysis of trophoblast cells and thus hindered the polarization of M2 macrophages. Further studies showed that AOC4P combines with tumor necrosis factor receptor-associated factor 6 (TRAF6) to upregulate TRAF6 expression. TRAF6 acted as an E3 ubiquitin ligase to promote ubiquitination and degradation of zeste homolog 2 (EZH2). These results provided new insights into the important role played by AOC4P at the maternal-fetal interface.

Immune Regulation of Seminal Plasma on the Endometrial Microenvironment: Physiological and Pathological Conditions.

Seminal plasma (SP) accounts for more than 90% of semen volume. It induces inflammation, regulates immune tolerance, and facilitates embryonic development and implantation in the female reproductive tract. In the physiological state, SP promotes endometrial decidualization and causes changes in immune cells such as macrophages, natural killer cells, regulatory T cells, and dendritic cells. This leads to the secretion of cytokines and chemokines and also results in the alteration of miRNA profiles and the expression of genes related to endometrial tolerance and angiogenesis. Together, these changes modulate the endometrial immune microenvironment and contribute to implantation and pregnancy. However, in pathological situations, abnormal alterations in SP due to advanced age or poor diet in men can interfere with a woman's immune adaptation to pregnancy, negatively affecting embryo implantation and even the health of the offspring. Uterine pathologies such as endometriosis and endometritis can cause the endometrium to respond negatively to SP, which can further contribute to pathological progress and interfere with conception. The research on the mechanism of SP in the endometrium is conducive to the development of new targets for intervention to improve reproductive outcomes and may also provide new ideas for semen-assisted treatment of clinical infertility.

CTRP6 regulates M1 macrophage polarization via the PPAR-γ/NF-κB pathway and reprogramming glycolysis in recurrent spontaneous abortion.

Aberrant polarization and functions of decidual macrophages are closely related to recurrent spontaneous abortion (RSA). C1q/tumor necrosis factor-related protein 6 (CTRP6) is a member of the adiponectin paralog family, and plays indispensable roles in inflammation, glucose uptake and tumor metastasis. However, the regulatory effect of CTRP6 on macrophage polarization and glycolysis in RSA and the underlying mechanisms have not been fully elucidated. In the present study, we first found that CTRP6 expression was positively correlated with the M1 macrophage marker (CD86) in decidual tissues by dual immunofluorescence analysis. In vitro experiments indicated that CTRP6 could facilitate M1 macrophage activation through the PPAR-γ/NF-κB pathway and manipulate the glycolysis of macrophages. Notably, in addition to silencing CTRP6, treatment with a PPAR-γ agonist (GW1929) inhibited M1 macrophage polarization and rescued embryo absorption in vivo. Taken together, these results identify previously unrevealed functions of CTRP6 in macrophage transformation during RSA.

A Ferroptosis-Related lncRNAs Signature Predicts Prognosis of Colon Adenocarcinoma.

(1) Ferroptosis is a type of cellular death caused by lipid-dependent iron peroxide, which plays a major role in cancer. Long noncoding RNAs (lncRNAs) are increasingly recognized as key regulating substances in ferroptosis; (2) RNA sequencing expressions and clinical data of 519 patients with colon adenocarcinoma (COAD) were downloaded from The Cancer Genome Atlas (TCGA) database. The expression levels of lncRNAs related to ferroptosis were screened with Pearson correlation analysis. Differential genes were enriched with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. LncRNAs related to ferroptosis were determined with univariate Cox regression and multivariate Cox regression analyses, and patients with COAD were classified into high- and low-risk subgroups according to their median risk score. The prognostic value was further examined, and the association between ferroptosis-related lncRNAs (frlncRNAs) and survival in patients with high and low risks of COAD was validated. A TCGA-COAD data set was used for receiver operating characteristic (ROC) analysis and detrended correspondence analysis (DCA) to assess prediction accuracy. Finally, a nomogram was constructed to predict survival probability; (3) We obtained a model consisting of a five-frlncRNAs signature comprising AP003555.1, AP001469.3, ITGB1-DT, AC129492.1, and AC010973.2 for determining the overall survival (OS) of patients with COAD. The survival analysis and ROC curves showed that the model had good robustness and predictive performance on the TCGA training set; (4) We found that a five-frlncRNAs signature may play a potential role in anti-COAD immunity. Risk characteristics based on frlncRNAs can accurately predict the prognosis and immunotherapy response of patients with COAD.

Association of Unhealthy Lifestyle and Genetic Risk Factors With Mild Cognitive Impairment in Chinese Older Adults.

Importance: Apolipoprotein E polymorphism ε4 (APOE ε4) and methylenetetrahydrofolate reductase (MTHFR) TT genotype are genetic risk factors of mild cognitive impairment (MCI), but whether this risk can be changed by modifiable lifestyle factors is unknown. Objective: To explore whether unhealthy lifestyle (unhealthy dietary intake, current smoking, nonlimited alcohol consumption, and irregular physical activities) is associated with a higher risk of age-related MCI considering genetic risk. Design, Setting, and Participants: This population-based cohort study used data from Tianjin Elderly Nutrition and Cognition (TENC) study participants, recruited from March 1, 2018, through June 30, 2021, and followed up until November 30, 2022. Participants were Chinese adults aged 60 years or older who completed the neuropsychological assessments, general physical examinations, and a personal interview. Exposures: Healthy lifestyle was defined according to the Chinese Dietary Guidelines 2022, including healthy diet, regular physical activity, limited alcohol consumption, and no current smoking, categorized into healthy and unhealthy lifestyles according to weighted standardized lifestyle score. Genetic risk was defined by MTHFR TT genotype and APOE ε4, categorized into low and high genetic risk according to weighted standardized genetic risk score. Main Outcomes and Measures: The main outcome was newly diagnosed MCI as identified using a modified version of Petersen criteria. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazard regression models. Results: A total of 4665 participants were included (mean [SD] age, 67.9 [4.9] years; 2546 female [54.6%] and 2119 male [45.4%]); 653 participants with new-onset MCI (mean [SD] age, 68.4 [5.4] years; 267 female [40.9%] and 386 male [59.1%]) were identified after a median follow-up of 3.11 years (range, 0.82-4.61 years). Individuals with a low genetic risk and an unhealthy lifestyle (HR, 3.01; 95% CI, 2.38-3.79), a high genetic risk and a healthy lifestyle (HR, 2.65; 95% CI, 2.03-3.44), and a high genetic risk and an unhealthy lifestyle (HR, 3.58; 95% CI, 2.73-4.69) had a higher risk of MCI compared with participants with a low genetic risk and a healthy lifestyle. There was a synergistic interaction between lifestyle categories and genetic risk (ß = 3.58; 95% CI, 2.73-4.69). Conclusions and Relevance: In this cohort study of TENC participants, the findings show that unhealthy lifestyle and high genetic risk were significantly associated with a higher risk of MCI among Chinese older adults. Unhealthy lifestyle factors were associated with a higher risk of MCI regardless of genetic risk, and lifestyle and genetic risk had synergistic interactions. These findings could contribute to the development of dietary guidelines and the prevention of early-stage dementia.

Accumulation, migration and health risk of trace metals in a soil-strawberry-human system of the Yangtze River Delta region, China.

Growing concern has been paid to metals in soil-strawberry system. In contrast, few attempts have been made to investigate bioaccessible metals in strawberries and further assess health risk based on bioaccessible metals. Moreover, the connections between soil parameters (e.g. soil pH, organic matter (OM), total and bioavailable metals) and metal transfer in soil-strawberry-human system still need to be systematically investigated as well. Considering that strawberries are extensively grown under plastic-shed conditions in China, a total of 18 paired plastic-shed soil (PSS) and strawberry samples were taken from the strawberry bases located in the Yangtze River Delta of China as a case study to assess accumulation status, migration and health risk of Cd, Cr, Cu, Ni, Pb, and Zn in the PSS-strawberry-human system. Overall, heavy application of organic fertilizers induced accumulation and contamination of Cd and Zn in PSS. In particular, 55.6% and 44.4% of PSS samples had considerable and moderate ecological risk caused by Cd, respectively. Despite no metal pollution in strawberry, PSS acidification mainly caused by high nitrogen input promoted Cd and Zn uptake by strawberry and enhanced bioaccessible concentrations of Cd, Cu, and Ni. In contrast, the increased soil OM caused by organic fertilizer application decreased Zn migration in PSS-strawberry-human system. Additionally, bioaccessible metals in strawberries induced limited non-cancer and cancer risk. To mitigate accumulation of Cd and Zn in PSS and metal transfer in the food chain, feasible fertilization strategies should be developed and carried out.

Deep learning-based classification and segmentation for scalpels.

PURPOSE: Scalpels are typical tools used for cutting in surgery, and the surgical tray is one of the locations where the scalpel is present during surgery. However, there is no known method for the classification and segmentation of multiple types of scalpels. This paper presents a dataset of multiple types of scalpels and a classification and segmentation method that can be applied as a first step for validating segmentation of scalpels and further applications can include identifying scalpels from other tools in different clinical scenarios. METHODS: The proposed scalpel dataset contains 6400 images with labeled information of 10 types of scalpels, and a classification and segmentation model for multiple types of scalpels is obtained by training the dataset based on Mask R-CNN. The article concludes with an analysis and evaluation of the network performance, verifying the feasibility of the work. RESULTS: A multi-type scalpel dataset was established, and the classification and segmentation models of multi-type scalpel were obtained by training the Mask R-CNN. The average accuracy and average recall reached 94.19% and 96.61%, respectively, in the classification task and 93.30% and 95.14%, respectively, in the segmentation task. CONCLUSION: The first scalpel dataset is created covering multiple types of scalpels. And the classification and segmentation of multiple types of scalpels are realized for the first time. This study achieves the classification and segmentation of scalpels in a surgical tray scene, providing a potential solution for scalpel recognition, localization and tracking.

Remediation of copper and lead contaminated sediments using iron-based granule biochar: mechanisms and enzyme activity.

In recent years, there has been a growing concern about heavy metal contamination in sediments. In this study, iron-based granular biochar (MGB) is prepared to remediate Cu and Pb contaminated sediments. Characterizations via scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR) show that the rough surface of MGB with abundant pore structures and a large number of oxygen-containing functional groups that facilitate stabilization of Cu and Pb in sediments. Potential mobility and bioavailability of Cu and Pb are investigated using BCR sequential extraction in the 35 day remediation experiment. The XPS results indicate that FeOOH and C-OH play a crucial part in stabilizing heavy metals. Large affinity of FeOOH for Pb allows it to occupy a proportion in F2 while C-OH is attractive to Cu. Changes of pH, organic matter (OM), and available phosphorus (AP) in sediments after adding MGB as well as the relationship between changes and the stable solidification of Cu and Pb are explored. The stable solidification of heavy metals effectively reduces the available phosphorus in sediments. Magnetic and particle properties of the material are used to reduce the impact of MGB aging on sediment environment and separate it from the remediated sediment. Finally, 3% of MGB significantly enhanced the sediment catalase activity in the biological enzyme activity experiment. All findings indicate that MGB is a green and environmentally friendly sediment remediation material with satisfactory potential in synergistically stabilizing heavy metals and phosphorus.Highlights The complexation of FeOOH with Pb on the surface of MGB fixes it to the reduced stateThe C-OH on the surface of MGB is more attractive to Cu than PbMGB effectively mitigates the release of bioavailable phosphorus from sediments to overlying water.

Potential use of hydroxyapatite combined with hydrated lime or zeolite to promote growth and reduce cadmium transfer in the soil-celery-human system.

Although hydroxyapatite (HAP) can prominently lower Cd uptake by celery from Cd-polluted soil, its high application rates in reality may lead to high cost and potential environmental risk. Therefore, we aimed to clarify whether combined amendments of HAP and another low-cost material (hydrated lime, corn straw-derived biochar, or zeolite) with reduced application rate of each single amendment could significantly decrease Cd transfer in soil-celery-human system without side effect on celery growth through a pot experiment. Results revealed that adding biochar, HAP, zeolite, or combined amendments had no obvious side effect on celery growth, while adding 0.3% hydrated lime significantly decreased fresh edible celery yield by 69.0%. Conversely, adding 0.5% HAP + 0.05% hydrated lime increased fresh edible celery yield by 39.8%. Additionally, adding HAP, zeolite, or hydrated lime rather than adding biochar effectively decreased total and bioaccessible Cd in edible celery. Similarly, HAP + hydrated lime and HAP + zeolite were much more efficient than HAP + biochar in lowering Cd transfer in soil-celery-human system. The total and bioaccessible Cd in edible celery were even reduced by over 50.0% after adding HAP + hydrated lime or HAP + zeolite at low rates. Considering the effects on celery growth and Cd transfer, HAP + hydrated lime and HAP + zeolite have the potential in remediating soil Cd contamination.

Autonomous aspirating robot for removing saliva blood mixed liquid in oral surgery.

Saliva blood mixed liquid (SBML) appears in oral surgery, such as scaling and root planning, and it affects surgical vision and causes discomfort to the patient. However, removing SBML, i.e. frequent aspiration of the mixed liquid, is a routine task involving heavy workload and interruption of oral surgery. Therefore, it is valuable to alternate the manual mode by autonomous robotic technique. The robotic system is designed consisting of an RGB-D camera, a manipulator, a disposable oral aspirator. An algorithm is developed for detection of SBML. Path planning method is also addressed for the distal end of the aspirator. A workflow for removing SBML is presented. 95% of the area of the SBML in the oral cavity was removed after liquid aspiration among a group of ten SBML aspiration experiments. This study provides the first result of the autonomous aspirating robot (AAR) for removing SBML in oral surgery, demonstrating that SBML can be removed by the autonomous robot, freeing stomatology surgeon from tedious work.

Integrating clinical and cross-cohort metagenomic features: a stable and non-invasive colorectal cancer and adenoma diagnostic model.

Background: Dysbiosis is associated with colorectal cancer (CRC) and adenomas (CRA). However, the robustness of diagnostic models based on microbial signatures in multiple cohorts remains unsatisfactory. Materials and Methods: In this study, we used machine learning models to screen metagenomic signatures from the respective cross-cohort datasets of CRC and CRA (selected from CuratedMetagenomicData, each disease included 4 datasets). Then select a CRC and CRA data set from the CuratedMetagenomicData database and meet the requirements of having both metagenomic data and clinical data. This data set will be used to verify the inference that integrating clinical features can improve the performance of microbial disease prediction models. Results: After repeated verification, we selected 20 metagenomic features that performed well and were stably expressed within cross-cohorts to represent the diagnostic role of bacterial communities in CRC/CRA. The performance of the selected cross-cohort metagenomic features was stable for multi-regional and multi-ethnic populations (CRC, AUC: 0.817-0.867; CRA, AUC: 0.766-0.833). After clinical feature combination, AUC of our integrated CRC diagnostic model reached 0.939 (95% CI: 0.932-0.947, NRI=30%), and that of the CRA integrated model reached 0.925 (95%CI: 0.917-0.935, NRI=18%). Conclusion: In conclusion, the integrated model performed significantly better than single microbiome or clinical feature models in all cohorts. Integrating cross-cohort common discriminative microbial features with clinical features could help construct stable diagnostic models for early non-invasive screening for CRC and CRA.

The FUS/circEZH2/KLF5/ feedback loop contributes to CXCR4-induced liver metastasis of breast cancer by enhancing epithelial-mesenchymal transition.

BACKGROUND: Metastasis of breast cancer have caused the majority of cancer-related death worldwide. The circRNAs are associated with tumorigenesis and metastasis in breast cancer according to recent research. However, the biological mechanism of circRNAs in liver metastatic breast cancer remains ambiguous yet. METHODS: Microarray analysis of three pairs of primary BC tissues and matched hepatic metastatic specimens identified circEZH2. We used RT-qPCR and FISH assays to confirm circEZH2 existence, characteristics, and expression. Both in vivo and in vitro, circEZH2 played an oncogenic role which promoted metastasis as well. A range of bioinformatic analysis, Western blot, RNA pull-down, RIP, ChIP, and animal experiments were used to define the feedback loop involving FUS, circEZH2, miR-217-5p, KLF5, FUS, CXCR4 as well as epithelial and mesenchymal transition. RESULTS: In our research, circEZH2 was proved to be upregulated in liver metastases in BC and predicted the worse prognosis in breast cancer patients. Overexpression of circEZH2 notably accentuated the vitality and invasion of BC cells, whereas knockdown of circEZH2 elicited the literally opposite effects. Besides, overexpressed circEZH2 promoted tumorigenesis and liver metastasis in vivo. Moreover, circEZH2 could adsorb miR-217-5p to upregulate KLF5 thus leading to activate FUS transcription which would facilitate the back-splicing program of circEZH2. Meanwhile, KLF5 could upregulated CXCR4 transcriptionally to accelerate epithelial and mesenchymal transition of breast cancer. CONCLUSIONS: Consequently, a novel feedback loop FUS/circEZH2/KLF5/CXCR4 was established while circEZH2 could be novel biomarker and potential target for BC patients' therapy.

Prognosis and Dissection of Immunosuppressive Microenvironment in Breast Cancer Based on Fatty Acid Metabolism-Related Signature.

Fatty acid metabolism has been deciphered to augment tumorigenesis and disease progression in addition to therapy resistance via strengthened lipid synthesis, storage, and catabolism. Breast cancer is strongly associated with the biological function of fatty acid metabolism owing to the abundant presence of adipocytes in breast tissue. It has been unraveled that tumor cells exhibit considerable plasticity based on fatty acid metabolism, responding to extra-tumoral and a range of metabolic signals, in which tumor microenvironment plays a pivotal role. However, the prognostic significance of fatty acid metabolism in breast cancer remains to be further investigated. Alongside these insights, we retrieved 269 reliable fatty acid metabolism-related genes (FMGs) and identified the landscape of copy number variations and expression level among those genes. Additionally, 11 overall survival-related FMGs were clarified by univariate Cox hazards regression analysis in The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Subsequently, a prognostic signature based on 6 overall survival (OS)-related FMGs was generated using Lasso Cox hazards regression analysis in TCGA dataset and was validated in two external cohorts. The correlation between the signature and several essential clinical parameters, including T, N, and PAM50 subtypes, was unveiled by comparing the accumulating signature value in various degrees. Furthermore, an optimal nomogram incorporating the signature, age, and American Joint Committee on Cancer (AJCC) stage was constructed, and the discrimination was verified by C-index, the calibration curve, and the decision curve analysis. The underlying implications for immune checkpoints inhibitors, the landscape of tumor immune microenvironment, and the predictive significance in therapy resistance to diverse strategies were depicted ultimately. In conclusion, our findings indicate the potential prognostic connotation of fatty acid metabolism in breast cancer, supporting novel insights into breast cancer patients' prognosis and administrating effective immunotherapy.