HVS-Unsup: Unsupervised cervical cell instance segmentation method based on human visual simulation.

Instance segmentation plays an important role in the automatic diagnosis of cervical cancer. Although deep learning-based instance segmentation methods can achieve outstanding performance, they need large amounts of labeled data. This results in a huge consumption of manpower and material resources. To solve this problem, we propose an unsupervised cervical cell instance segmentation method based on human visual simulation, named HVS-Unsup. Our method simulates the process of human cell recognition and incorporates prior knowledge of cervical cells. Specifically, firstly, we utilize prior knowledge to generate three types of pseudo labels for cervical cells. In this way, the unsupervised instance segmentation is transformed to a supervised task. Secondly, we design a Nucleus Enhanced Module (NEM) and a Mask-Assisted Segmentation module (MAS) to address problems of cell overlapping, adhesion, and even scenarios involving visually indistinguishable cases. NEM can accurately locate the nuclei by the nuclei attention feature maps generated by point-level pseudo labels, and MAS can reduce the interference from impurities by updating the weight of the shallow network through the dice loss. Next, we propose a Category-Wise droploss (CW-droploss) to reduce cell omissions in lower-contrast images. Finally, we employ an iterative self-training strategy to rectify mislabeled instances. Experimental results on our dataset MS-cellSeg, the public datasets Cx22 and ISBI2015 demonstrate that HVS-Unsup outperforms existing mainstream unsupervised cervical cell segmentation methods.

Defect-driven nanostructuring of low-nuclearity Pt-Mo ensembles for continuous gas-phase formic acid dehydrogenation.

Supported metal clusters comprising of well-tailored low-nuclearity heteroatoms have great potentials in catalysis owing to the maximized exposure of active sites and metal synergy. However, atomically precise design of these architectures is still challenging for the lack of practical approaches. Here, we report a defect-driven nanostructuring strategy through combining defect engineering of nitrogen-doped carbons and sequential metal depositions to prepare a series of Pt and Mo ensembles ranging from single atoms to sub-nanoclusters. When applied in continuous gas-phase decomposition of formic acid, the low-nuclearity ensembles with unique Pt3Mo1N3 configuration deliver high-purity hydrogen at full conversion with unexpected high activity of 0.62 molHCOOH molPt-1 s-1 and remarkable stability, significantly outperforming the previously reported catalysts. The remarkable performance is rationalized by a joint operando dual-beam Fourier transformed infrared spectroscopy and density functional theory modeling study, pointing to the Pt-Mo synergy in creating a new reaction path for consecutive HCOOH dissociations.

Lin28a maintains a subset of adult muscle stem cells in an embryonic-like state.

During homeostasis and after injury, adult muscle stem cells (MuSCs) activate to mediate muscle regeneration. However, much remains unclear regarding the heterogeneous capacity of MuSCs for self-renewal and regeneration. Here, we show that Lin28a is expressed in embryonic limb bud muscle progenitors, and that a rare reserve subset of Lin28a+Pax7- skeletal MuSCs can respond to injury at adult stage by replenishing the Pax7+ MuSC pool to drive muscle regeneration. Compared with adult Pax7+ MuSCs, Lin28a+ MuSCs displayed enhanced myogenic potency in vitro and in vivo upon transplantation. The epigenome of adult Lin28a+ MuSCs showed resemblance to embryonic muscle progenitors. In addition, RNA-sequencing revealed that Lin28a+ MuSCs co-expressed higher levels of certain embryonic limb bud transcription factors, telomerase components and the p53 inhibitor Mdm4, and lower levels of myogenic differentiation markers compared to adult Pax7+ MuSCs, resulting in enhanced self-renewal and stress-response signatures. Functionally, conditional ablation and induction of Lin28a+ MuSCs in adult mice revealed that these cells are necessary and sufficient for efficient muscle regeneration. Together, our findings connect the embryonic factor Lin28a to adult stem cell self-renewal and juvenile regeneration.

High expression of HOXC6 predicts a poor prognosis and induces proliferation and inflammation in multiple myeloma cells.

BACKGROUND: Multiple myeloma (MM) is a common blood system malignance accompanied by monoclonal plasma cell hyperplasia. Homeobox C6 (HOXC6) acts as an oncogene in various cancers, but its function on MM is elusive. OBJECTIVE: The role of HOXC6 on MM development was clarified in this study. METHODS: HOXC6 expression and its clinical significance were determined in the peripheral blood samples collected from forty MM patients and thirty healthy adult volunteers. The overall survival was evaluated by Kaplan-Meier analysis with the log-rank test. Cell viability, proliferation and apoptosis were measured by CCK-8, EdU assay and Flow cytometry in U266 and MM.1R cells. Tumor growth was estimated by a xenograft assay. The apoptosis of tumor tissues was evaluated using TUNEL staining. The protein level in tissues was tested by immunohistochemistry. RESULTS: The HOXC6 expression was elevated in MM and high HOXC6 level was associated with the poor overall survival of MM. Besides, the HOXC6 expression was associated with hemoglobin level and ISS stage. Furthermore, silencing HOXC6 suppressed cell proliferation, induced cell apoptosis, and restrained the secretion of inflammatory factors (TNF-α, IL-6, and IL-8) in MM cells through inactivating the NF-κB pathway. Moreover, silencing HOXC6 suppressed the tumor growth of MM, the inflammatory factors levels, and the activation of NF-κB pathway but enhanced apoptosis in vivo. CONCLUSION: HOXC6 was elevated in MM and associated with poor survival. Knockdown of HOXC6 suppressed proliferation, inflammation and tumorigenicity of MM cells via inactivating the NF-κB pathway. HOXC6 may be a meaningful target for MM therapy.

Adult progenitor rejuvenation with embryonic factors.

During ageing, adult stem cells' regenerative properties decline, as they undergo replicative senescence and lose both their proliferative and differentiation capacities. In contrast, embryonic and foetal progenitors typically possess heightened proliferative capacities and manifest a more robust regenerative response upon injury and transplantation, despite undergoing many rounds of mitosis. How embryonic and foetal progenitors delay senescence and maintain their proliferative and differentiation capacities after numerous rounds of mitosis, remains unknown. It is also unclear if defined embryonic factors can rejuvenate adult progenitors to confer extended proliferative and differentiation capacities, without reprogramming their lineage-specific fates or inducing oncogenic transformation. Here, we report that a minimal combination of LIN28A, TERT, and sh-p53 (LTS), all of which are tightly regulated and play important roles during embryonic development, can delay senescence in adult muscle progenitors. LTS muscle progenitors showed an extended proliferative capacity, maintained a normal karyotype, underwent myogenesis normally, and did not manifest tumorigenesis nor aberrations in lineage differentiation, even in late passages. LTS treatment promoted self-renewal and rescued the pro-senescence phenotype of aged cachexia patients' muscle progenitors, and promoted their engraftment for skeletal muscle regeneration in vivo. When we examined the mechanistic basis for LIN28A's role in the LTS minimum combo, let-7 microRNA suppression could not fully explain how LIN28A promoted muscle progenitor self-renewal. Instead, LIN28A was promoting the translation of oxidative phosphorylation mRNAs in adult muscle progenitors to optimize mitochondrial reactive oxygen species (mtROS) and mitohormetic signalling. Optimized mtROS induced a variety of mitohormetic stress responses, including the hypoxic response for metabolic damage, the unfolded protein response for protein damage, and the p53 response for DNA damage. Perturbation of mtROS levels specifically abrogated the LIN28A-driven hypoxic response in Hypoxia Inducible Factor-1α (HIF1α) and glycolysis, and thus LTS progenitor self-renewal, without affecting normal or TS progenitors. Our findings connect embryonically regulated factors to mitohormesis and progenitor rejuvenation, with implications for ageing-related muscle degeneration.

The interaction effects of pesticides with Saccharomyces cerevisiae and their fate during wine-making process.

Pesticide residues in grapes could be transferred to fermentation system during the wine-making process, which may interfere the normal proliferation of Saccharomyces cerevisiae and subsequently affect the safety and quality of wine products. However, the interaction between pesticides and Saccharomyces cerevisiae is still poorly understood. Herein, the fate, distribution and interaction effect with Saccharomyces cerevisiae of five commonly-used pesticides during the wine-making process were evaluated. The five pesticides exerted varied inhibition on the proliferation of Saccharomyces cerevisiae, and the order of inhibition intensity was difenoconazole > tebuconazole > pyraclostrobin > azoxystrobin > thiamethoxam. Compared with the other three pesticides, triazole fungicides difenoconazole and tebuconazole showed stronger inhibition and played a major role in binary exposure. The mode of action, lipophilicity and exposure concentration were important factors in the inhibition of pesticides. Saccharomyces cerevisiae had no obvious impacts on the degradation of target pesticides in the simulated fermentation experiment. However, the levels of target pesticides and their metabolite were significantly reduced during the wine-making process, with the processing factors ranged from 0.030 to 0.236 (or 0.032 to 0.257) during spontaneous (or inoculated) wine-making process. As a result, these pesticides were significantly enriched in the pomace and lees, and showed a positive correlation (R2 ≥ 0.536, n = 12, P < 0.05) between the hydrophobicity of pesticides and distribution coefficients in the solid-liquid distribution system. The findings provide important information for rational selection of pesticides on wine grapes and facilitate more accurate risk assessments of pesticides for grape processing products.

Residual levels of five pesticides in peanut oil processing and chips frying.

BACKGROUND: Pesticide contamination in oil crops and processed products is an important food safety concern. The study was aimed to investigate the pesticide residue changes in press processing of peanut oil and frying of chips. RESULTS: Five pesticides - chlorpyrifos, deltamethrin, methoxyfenozide, azoxystrobin and propargite - which are often applied during growth period in peanut plants, were selected to investigate their residue changes in cold press processing of peanut oil and frying of potato chips. Results showed that the residues of the five pesticides were decreased by 3.1-42.6% during air-drying before oil pressing. The residues of chlorpyrifos, deltamethrin, methoxyfenozide and propargite in peanut oil were 2.05-3.63 times higher than that in peanut meal after cold pressing of the oil, except for azoxystrobin having a slightly lower residue in peanut oil, with 0.92 times that in peanut meal. The processing factors of the five pesticides in peanut oil ranged from 1.17 to 2.73 and were highly related to the log Kow of the pesticides. The higher the log Kow , the more easily was the pesticide partitioned in the peanut oil. Besides, as frying time increase during preparation of chips, the concentration of pesticides in peanut oil decreased gradually by 6.7-22.1% compared to the first frying. In addition, 0.47-11.06% of the pesticides were transferred to the chips through frying with contaminated oil. CONCLUSION: This is first report showing that pesticides can transfer from contaminated oil to chips. There exists a potential dietary health risk by using pesticide-contaminated oil for frying chips. This work could provide basic data for accurate dietary risk assessment of pesticide residues in peanut oil and its frying products. © 2021 Society of Chemical Industry.