Deep learning-based pathological prediction of lymph node metastasis for patient with renal cell carcinoma from primary whole slide images.

BACKGROUND: Metastasis renal cell carcinoma (RCC) patients have extremely high mortality rate. A predictive model for RCC micrometastasis based on pathomics could be beneficial for clinicians to make treatment decisions. METHODS: A total of 895 formalin-fixed and paraffin-embedded whole slide images (WSIs) derived from three cohorts, including Shanghai General Hospital (SGH), Clinical Proteomic Tumor Analysis Consortium (CPTAC) and Cancer Genome Atlas (TCGA) cohorts, and another 588 frozen section WSIs from TCGA dataset were involved in the study. The deep learning-based strategy for predicting lymphatic metastasis was developed based on WSIs through clustering-constrained-attention multiple-instance learning method and verified among the three cohorts. The performance of the model was further verified in frozen-pathological sections. In addition, the model was also tested the prognosis prediction of patients with RCC in multi-source patient cohorts. RESULTS: The AUC of the lymphatic metastasis prediction performance was 0.836, 0.865 and 0.812 in TCGA, SGH and CPTAC cohorts, respectively. The performance on frozen section WSIs was with the AUC of 0.801. Patients with high deep learning-based prediction of lymph node metastasis values showed worse prognosis. CONCLUSIONS: In this study, we developed and verified a deep learning-based strategy for predicting lymphatic metastasis from primary RCC WSIs, which could be applied in frozen-pathological sections and act as a prognostic factor for RCC to distinguished patients with worse survival outcomes.

A MDM2 inhibitor MX69 inhibits adipocytes adipogenesis and differentiation.

Adipose tissue, a key regulator of systemic energy homeostasis, can synthesize and store triglycerides to meet long-term energy demands. In response to nutrient overload, adipose tissue expands by hypertrophy or hyperplasia. As an oncogene, MDM2 has exerted diverse biological activities including human development, tissue regeneration, and inflammation, in addition to major oncogenic activities. Recently, some studies indicated that MDM2 plays an important role in adipose tissue function. However, the role of MX69, a MDM2 inhibitor, in adipose tissue function has not been fully elucidated. Here, we administered MX69 intraperitoneally to high-fat diet-induced obesity (DIO) wild type C57BL/6 mice and found that MX69 could promote the body weight and white adipose tissue weight of DIO mice. Moreover, MX69 had no effects on glucose tolerance and insulin sensitivity in DIO mice. And MX69 treatment decreased the size of adipocytes and fat deposition in adipose tissue and inhibited 3T3-L1 preadipocytes differentiation. Mechanistically, MX69 inhibited the protein levels of MDM2 and the mRNA levels of genes related to adipogenesis and differentiation. In summary, our results indicated that MDM2 has a crucial and complex role in regulating adipose tissue function.

Anti-tumor compounds identification from gossypol Groebke imidazopyridine product.

Series of imidazo[1,2-a]pyridines designed from gossypol modification based on Groebke-Blackburn-Bienaymé reaction were discovered as potent Bcl-2 inhibitors. Compound 4 was found to display good anti-proliferative activities for 7 human cancer cell lines (0.33-1.7 µM) among them, which were better than separate gossypol and imidazopyridine moiety compounds. It was capable of suppressing antiapoptotic proteins Bcl-2 and Bcl-XL demonstrated by mechanism studies, and possible binding model was also illustrated by molecular modelling.

Topography-induced symmetry transition of droplets on quasi-periodically patterned surfaces.

Quasi-periodic structures of quasicrystals yield novel effects in diverse systems. However, there is little investigation on employing quasi-periodic structures in morphology control. Here, we show the use of quasi-periodic surface structures in controlling the transition of liquid droplets. Although surface structures seem random-like, we find that on these surfaces, droplets spread to well-defined 5-fold symmetric shapes and the symmetry of droplet shapes spontaneously restores during spreading, hitherto unreported in the morphology control of droplets. To obtain physical insights into these symmetry transitions, we conduct energy analysis and perform systematic experiments by varying the properties of both liquid droplets and patterned surfaces. The results show the dominant factors in determining droplet shapes to be surface topography and the self-similarity of the surface structure. Quantified results of the droplet spreading process show distinct dynamics from the spreading experiments on periodically micropatterned surfaces. Our findings significantly advance the control capability of the droplet morphology. Such a quasi-periodic patterning strategy can offer a new method to achieve complex patterns, and may be used to model patterns in the study of rough surfaces.

Biosynthesis of mannose from glucose via constructing phosphorylation-dephosphorylation reactions in Escherichia coli.

d-mannose has been widely used in food, medicine, cosmetic, and food-additive industries. To date, chemical synthesis or enzymatic conversion approaches based on iso/epimerization reactions for d-mannose production suffered from low conversion rate due to the reaction equilibrium, necessitating intricate separation processes for obtaining pure products on an industrial scale. To circumvent this challenge, this study showcased a new approach for d-mannose synthesis from glucose through constructing a phosphorylation-dephosphorylation pathway in an engineered strain. Specifically, the gene encoding phosphofructokinase (PfkA) in glycolytic pathway was deleted in Escherichia coli to accumulate fructose-6-phosphate (F6P). Additionally, one endogenous phosphatase, YniC, with high specificity to mannose-6-phosphate, was identified. In ΔpfkA strain, a recombinant synthetic pathway based on mannose-6-phosphate isomerase and YniC was developed to direct F6P to mannose. The resulting strain successfully produced 25.2 g/L mannose from glucose with a high conversion rate of 63% after transformation for 48 h. This performance surpassed the 15% conversion rate observed with 2-epimerases. In conclusion, this study presents an efficient method for achieving high-yield mannose synthesis from cost-effective glucose.

Metabarcoding Analysis of Microorganisms Inside Household Washing Machines in Shanghai, China.

Washing machines are one of the tools that bring great convenience to people's daily lives. However, washing machines that have been used for a long time often develop issues such as odor and mold, which can pose health hazards to consumers. There exists a conspicuous gap in our understanding of the microorganisms that inhabit the inner workings of washing machines. In this study, samples were collected from 22 washing machines in Shanghai, China, including both water eluted from different parts of washing machines and biofilms. Quantitative qualitative analysis was performed using fluorescence PCR quantification, and microbial communities were characterized by high-throughput sequencing (HTS). This showed that the microbial communities in all samples were predominantly composed of bacteria. HTS results showed that in the eluted water samples, the bacteria mainly included Pseudomonas, Enhydrobacter, Brevibacterium, and Acinetobacter. Conversely, in the biofilm samples, Enhydrobacter and Brevibacterium were the predominant bacterial microorganisms. Correlation analysis results revealed that microbial colonies in washing machines were significantly correlated with years of use and the type of detergent used to clean the washing machine. As numerous pathogenic microorganisms can be observed in the results, effective preventive measures and future research are essential to mitigate these health problems and ensure the continued safe use of these household appliances.

Development of a spectrum-based ship fuel sulfur content real-time evaluation method.

Although maritime transport plays an essential role in the global economy, it inevitably imposes negative impacts on our living environment, especially for ships using fuel with high sulfur content. Nowadays, ship emission monitoring highly depends on manual inspection, which is time-consuming and labor-intensive. This study proposes a decision framework based on spectrum technology and the sulfur­carbon ratio method to measure the ship fuel sulfur content. Specifically, after the Gaussian plume model optimization from four aspects, a multistep-based emission contribution evaluation method is developed to improve the evaluation accuracy. The proposed framework is validated by a suspected ship and a series of exempted ships from the Maritime Safety Administration in Nanjing, China. The validation results imply that the proposed framework has a certain enhancement in detection rate, evaluation accuracy and extensibility. It may provide an efficient and accurate supervision approach for the Maritime Safety Administration on ship fuel sulfur content measurement.

Nutritional Value and Physicochemical Characteristics of Alternative Protein for Meat and Dairy-A Review.

In order to alleviate the pressure on environmental resources faced by meat and dairy production and to satisfy the increasing demands of consumers for food safety and health, alternative proteins have drawn considerable attention in the food industry. However, despite the successive reports of alternative protein food, the processing and application foundation of alternative proteins for meat and dairy is still weak. This paper summarizes the nutritional composition and physicochemical characteristics of meat and dairy alternative proteins from four sources: plant proteins, fungal proteins, algal proteins and insect proteins. The difference between these alternative proteins to animal proteins, the effects of their structural features and environmental conditions on their properties, as well as the corresponding mechanism are compared and discussed. Though fungal proteins, algal proteins and insect proteins have shown some advantages over traditional plant proteins, such as the comparable protein content of insect proteins to meat, the better digestibility of fungal proteins and the better foaming properties of algal proteins, there is still a big gap between alternative proteins and meat and dairy proteins. In addition to needing to provide amino acid composition and digestibility similar to animal proteins, alternative proteins also face challenges such as maintaining good solubility and emulsion properties. Their nutritional and physicochemical properties still need thorough investigation, and for commercial application, it is important to develop and optimize industrial technology in alternative protein separation and modification.

Murine double minute 2 aggravates adipose tissue dysfunction through ubiquitin-mediated six-transmembrane epithelial antigen of prostate 4 degradation.

Healthy adipose tissue is crucial to maintain normal energy homeostasis. Little is known about the role of murine double minute 2 (MDM2), an E3 ubiquitin ligase and has been highlighted in oncopathology, in adipose tissue. Our results indicated that MDM2 expression was associated with nutritional status. Mdm2 adipocyte-specific knock-in (Mdm2-AKI) mice exhibited exacerbated weight gain, insulin resistance, and decreased energy expenditure. Meanwhile, chronic high-fat diet (HFD) exposure caused obvious epididymal white adipose tissue (eWAT) dysfunction, such as senescence, apoptosis, and chronic inflammation, thereby leading to hepatic steatosis in Mdm2-AKI mice. Mechanically, MDM2 could interact with six-transmembrane epithelial antigen of prostate 4 (STEAP4) and inhibit STEAP4 expression through ubiquitin-mediated STEAP4 degradation. Thereinto, the K18 and K161 sites of STEAP4 were ubiquitin-modificated by MDM2. Finally, STEAP4 restoration in eWAT of Mdm2-AKI mice on a HFD rescued MDM2-induced adipose dysfunction, insulin resistance, and hepatic steatosis. Summary, the MDM2-STEAP4 axis in eWAT plays an important role in maintaining healthy adipose tissue function and improving hepatic steatosis.

[One major QTL mapping and physical map construction for rolled leaf in rice].

A clonally propagated F2 population (F2CP), derived from the rice cross of Qimiaoxiang/91SP068, was used to map rolled leaf QTLs. As the parent Qimiaoxiang is an unrolling leaf variety, while 91SP068 is a medium rolling variety with about 34% rolling index. One major QTL, rl8, which came from 91SP068, was mapped between two flanking SSR markers, RM6954 and RM6841, on chromosome 5, with genetic distance 3.8 cM, and was 1.0 cM away from RM6954. Its additive effect estimated by composite interval mapping (CIM) was 9.61 in 2002 and 6.23 in 2003, and the dominance effect was also different between two years, -1.19 in 2002 and -4.44 in 2003, respectively. It explained about 20% - 33% of the total phenotypic variation between two years. Furthermore, an integrated physical and genetic map encompassing rl8 region was constructed, and the physical distance of the interval was 542 kb, and the ratio of physical to genetic distance was 144 kb/cM. Based on this research, fine mapping of rolled leaf QTLs will not only facilitate the map-based cloning of the gene itself, but also improve the efficiency of marker-assisted selection in plant breeding.